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4 - Physiology Main Handout Oct 2023

This document is a handout for physiology from Topnotch Medical Board Prep. It provides an overview and outline of the physiology content that will be covered, including modules on cell physiology, neurophysiology, cardiovascular physiology, and several other body systems. It notes that the handout is only valid for the October 2023 exam batch and will be updated for future batches. It also provides important legal information indicating the materials are protected by intellectual property law and outlines how the handouts should be treated with confidentiality.
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PDF, TXT or read online on Scribd
100% found this document useful (1 vote)
2K views99 pages

4 - Physiology Main Handout Oct 2023

This document is a handout for physiology from Topnotch Medical Board Prep. It provides an overview and outline of the physiology content that will be covered, including modules on cell physiology, neurophysiology, cardiovascular physiology, and several other body systems. It notes that the handout is only valid for the October 2023 exam batch and will be updated for future batches. It also provides important legal information indicating the materials are protected by intellectual property law and outlines how the handouts should be treated with confidentiality.
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PDF, TXT or read online on Scribd
You are on page 1/ 99

TOPNOTCH MEDICAL BOARD PREP PHYSIOLOGY MAIN HANDOUT BY DR. ENRICO PAOLO C.

BANZUELA
For inquiries visit www.topnotchboardprep.com.ph or https://www.facebook.com/topnotchmedicalboardprep/
This handout is only valid for October 2023 PLE batch. This will be rendered obsolete for the next batch since we update our handouts regularly.
MODULE PAGE
1. Cell and Muscle Physiology 1
IMPORTANT LEGAL INFORMATION 2. Neurophysiology 15
3. Cardiovascular Physiology 30
The handouts, videos and other review materials, provided by Topnotch Medical Board
Preparation Incorporated are duly protected by RA 8293 otherwise known as the Intellectual
4. Respiratory Physiology 42
Property Code of the Philippines, and shall only be for the sole use of the person: a) whose 5. Renal & Acid-base Physiology 53
name appear on the handout or review material, b) person subscribed to Topnotch Medical 6. Gastrointestinal Physiology 64
Board Preparation Incorporated Program or c) is the recipient of this electronic 7. Endocrine and Reproductive Physiology 73
communication. No part of the handout, video or other review material may be reproduced,
shared, sold and distributed through any printed form, audio or video recording, electronic 8. Hematology and Special Environments Physiology 87
medium or machine-readable form, in whole or in part without the written consent of
Topnotch Medical Board Preparation Incorporated. Any violation and or infringement,
whether intended or otherwise shall be subject to legal action and prosecution to the full
1. CELL & MUSCLE PHYSIOLOGY
extent guaranteed by law. 1. Cell Membranes
2. Transport Across Cell Membranes
3. Osmosis
DISCLOSURE 4. Diffusion Potential, Resting Membrane Potential, Action Potential
The handouts/review materials must be treated with utmost confidentiality. It shall be the
responsibility of the person, whose name appears therein, that the handouts/review 5. Neuromuscular and Synaptic Transmission
materials are not photocopied or in any way reproduced, shared, or lent to any person or 6. Skeletal Muscles
disposed in any manner. Any handout/review material found in the possession of another 7. Cardiac Muscles
person whose name does not appear therein shall be prima facie evidence of violation of RA 8. Smooth Muscles
8293. Topnotch review materials are updated every six (6) months based on the current
trends and feedback. Please buy all recommended review books and other materials listed 9. Comparison of Skeletal Muscles, Smooth Muscles and Cardiac Muscles
below.
THIS HANDOUT IS NOT FOR SALE!
1.1 CELL MEMBRANES
INSTRUCTIONS CELL
To scan QR codes on iPhone and iPad • basic unit of the human body (not the nucleus)
1. Launch the Camera app on your IOS device • First Step in cell reproduction: DNA Replication
2. Point it at the QR code you want to scan
3. Look for the notification banner at the top CELL NUMBER
of the screen and tap
Approximate number of human cells + bacterial
To scan QR codes on Android 68 trillion
1. Install QR code reader from Play Store cells inside the human body
2. Launch QR code app on your device Approximate number of human cells (80% are
3. Point it at the QR code you want to scan 30 trillion
RBCs – most abundant type of cell in the body)
4. Tap browse website
1 trillion Approximate number of glial (supporting) cells
Approximate number of neurons (actual value
A PRAYER FOR EXAMS 100 billion
closer to 86B)
TO ST. JOSEPH OF
Remember: major hallmarks of cancer: loss of cell-to-cell adhesion and
CUPERTINO (optional) anchorage independent growth
https://qrs.ly/ztebfz7 Dr. Banzuela
CELL MEMBRANE
Approach to Topnotch Physiology
• The Guardian of the Cell: divides the body into extracellular fluid
• Please buy the following: Physio BRS 6th ed and Ganong
(ECF) and intracellular fluid (ICF) compartments
Physiology 23rd ed or 25th ed, and Pre-Test Physiology 14th Ed
• Contains many protein, little carbohydrates, no water
o To be used as major reference books
• Semipermeable
o they’re very good books that will help you in this subject
o Lecture utilizes mainly Physio BRS supplemented by other • Has variable composition throughout the life of the cell
sources (e.g. Guyton, Berne and Levy, Ganong); those that you • More permeable to K+ rather than Na+
don’t understand or need further discussion, refer to Physio BRS • Loose carbohydrate coat of the cell surface: glycocalyx
and Ganong • Made up of a Lipid Bilayer (Fluid-Mosaic Model)
• We won’t try to cover all of physio; we’ll try to cover: o 55%: Proteins
o What you need as a General Physician (must-knows) o 25%: Phospholipids
o Less important topics that has been asked in the past (nice-to- § Outer Leaflet: Phosphatidylcholine, Sphingomyelin,
knows) § Inner Leaflet: Phosphatidylethanolamine,
• Guided highlighting system: highlight only those that are bold Phosphatidylserine, Phosphatidylinositol
and italicized → we’ve identified them for you o 13%: Cholesterol: confers membrane fluidity and permeability
• This handout is only for the one whose name appears as a to water-soluble substances
watermark. Videos are only for enrolled students. Handouts will § major lipoprotein source of cholesterol: low density lipoprotein
expire October 2023. (LDL)
o 4%: Other lipids: glycolipids confer antigenicity
o 3% Carbohydrates
This handout is only valid for the October 2023 PLE batch.
This will be rendered obsolete for the next batch Remember: cell membrane lets hydrophobic/fat-soluble substances to
since we update our handouts regularly. move in or out of the cell membrane with ease according to concentration
gradient. Imagine oxygen, carbon dioxide and steroid hormones directly
penetrating the cell membrane. The lipid bilayer basically allows fat-
MEDICAL PHYSIOLOGY soluble substances to move across it.
Example of a “nooks and crannies” question – question that is covered in
By Enrico Paolo C. Banzuela, MD, MSEd, MHPEd, FPSP the handout but commonly overlooked by the students since it is less
University of the Philippines College of Medicine Class 2005 important compared to essential physio concepts:
Master in Educational Entrepreneurship (MSEd), University of Pennsylvania Graduate Q: Loose carbohydrate coat of the cell surface
School of Education
A: Glycocalyx
Master in Health Professions Education (MHPEd), University of the Philippines Manila,
National Teacher Training Center for the Health Professions If you’ve read glycocalyx above but have glossed over it, be careful. Iba aral
Master of Health Professions Education (MHPE), University of Maastricht (current sa physio, iba aral sa boards.
student)
Management Development Program, Asian Institute of Management The format of this handout is meant to guide you while you are reading,
Postgraduate Certificate in Teaching Evidence-Based Healthcare, University of Oxford highlighting, or making your side notes.
Unit Head, Curriculum and Instructions, Office of Medical Education, San Beda University
Recommend that you only highlight what is in bold/italicized font in this
College of Medicine
Course Coordinator (Chairman) for Physiology, San Beda University College of Medicine handout, and for you to read the yellow boxes as if you are in a lecture.
Associate Professor II, San Beda College of Medicine Make your side notes at the back part of each page (the white blank page.
Guest Lecturer (Cell Module) Ateneo School of Medicine & Public Health Please refer to your Topnotch Online Primer for this).
Guest lecturer St, Luke’s Medical Center College of Medicine Dr. Banzuela

Physiology Teacher, Topnotch Medical Board Prep • Factors that determine permeability of the cell membrane
Co-Author, IM Platinum, Surgery Platinum, Pedia Platinum, Ob-Gyn Platinum o Temperature
Past President, Philippine Society of Physiologists (PSP)
Fellow, Philippine Society of Physiologists (PSP)
o Types of solutes present
o Level of cell hydration

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This handout is only valid for October 2023 PLE batch. This will be rendered obsolete for the next batch since we update our handouts regularly.
TOPNOTCH MEDICAL BOARD PREP PHYSIOLOGY MAIN HANDOUT BY DR. ENRICO PAOLO C. BANZUELA
For inquiries visit www.topnotchboardprep.com.ph or https://www.facebook.com/topnotchmedicalboardprep/
This handout is only valid for October 2023 PLE batch. This will be rendered obsolete for the next batch since we update our handouts regularly.
• Studded with the following proteins: Membrane transport of important substances:
o Integral Proteins • Protein hormones: binds to cell membrane receptors
§ Has tight attachment (needs detergent to remove) using • Steroid hormones: simple diffusion
hydrophobic interactions • Amino acids: Luminal Membrane: Na-AA (amino acid) symport,
Basolateral Membrane: facilitated diffusion
§ spans the entire cell membrane
• Water: aquaporins (water bridges/water channels)
§ e.g. Aquaporins, Ion Channels, Solute Carriers (GLUT, Dr. Banzuela
Symport, Antiport), ATP-dependent Transporters
o Peripheral Proteins
§ Has loose attachment using electrostatic interactions
§ Found in the inner leaflet or outer leaflet

© Topnotch Medical Board Prep © Topnotch Medical Board Prep

Look at the picture above. The integral proteins are TIGHTLY ATTACHED
and do not move. The peripheral proteins are loosely-attached and tend
to “float” in the lipid bilayer – like leaves or flowers floating in a pond.
Viewed externally – those peripheral proteins floating around gives the cell
a “mosaic” appearance, giving rise to the term “fluid-mosaic model”
Dr. Banzuela

• Movement of different substances across the cell membrane:


o Water
§ Undergoes Osmosis via Aquaporins
o Lipid-Soluble (Non-polar, Hydrophobic) Substances © Topnotch Medical Board Prep

§ Substances undergo Simple Diffusion


o Water-Soluble (Polar, Hydrophilic) Substances
§ Substances undergo Carrier-mediated Transport
INTERCELLULAR STRUCTURES BETWEEN CELL MEMBRANES
TYPE DESCRIPTION LOCATION NOTES
Macula Adherens Disk-shaped;
Epithelium Like intercellular stapler wires
(Desmosomes) For tight intercellular adhesion
Epithelial & endothelial cells Equivalent in cardiomyocytes is
Ring-shaped; Fascia Adherens
Zonula Adherens Intercalated disks of cardiac
Increases surface area for contact (ribbon-like patterns; doesn’t completely
muscles enclose cell)
Transcellular Transport:
Barrier to movement of proteins movement across apical and
Zonula Occludens Leaky: PCT, Jejunum
across membranes; divides cell into basolateral sides
(Tight Junctions) Tight: CD, terminal Colon, BBB
apical and basolateral side Paracellular Transport: movement
through TJ
bridge for sharing of small
Functional Unit: ConneXON (its
Gap Junctions molecules between cells; For rapid Cardiac and unitary smooth muscles
Subunit: ConneXIN)
intercellular communication
When you hear desmosomes, think STAPLER wires – they hold cells 1.2 TRANSPORT ACROSS CELL MEMBRANES
together in tight attachment. They make cells ADHERE to each other –
kaya tinatawag din siyang Macula ADHEREns. Gap Junctions – they enable
the cells to contract together as one. When you hear gap junctions, think
SYNCYTIUM – the ability of muscle cells to contract together as one. CELL TRANSPORT
https://qrs.ly/9oebfzg
Stratum Basale/Germinativum is separated from the dermis by the
basement membrane (basal lamina) and attached to the basement
membrane by HEMIDESMOSOMES.
Refer to this audio file while reading this very important table.
Bind adhesion proteins to the cytoskeleton within cardiac myocytes, thus Dr. Banzuela
connecting the cells: DESMOSOMES INSIDE INTERCALATED DISCS
TYPE MOVEMENT EXAMPLES
Hexagonal shaped structures responsible for intercellular communication
– connexon or gap junctions?
I. NON- CARRIER MEDIATED TRANSPORT
A: Connexon. Tricky question, since gap junctions are made up of connexon as High
Oxygen, Nitrogen, CO2,
units, but due to the “hexagon” shape requirement, best answer is connexon. concentration→
Simple alcohol, lipid
Dr. Banzuela Low
Diffusion hormones, anesthetic
Example of “cross-over trivial” questions – these unfortunately cannot be conconcentration
drugs
predicted since they are not important in physiology – that is why you (Passive; Downhill)
would also need to rely on what was taught to you in med school, and Divided in Pino- and
maraming dasal kay Lord: Phagocytosis
Endocytosis -
Q: Superficial layers of skin slip away from the lower layers after light e.g., Neutrophils and
rubbing; seen in pemphigus, toxic epidermal necrolysis, and staphylococcal Bacteria
scalded skin syndrome (SSSS) Exocytosis - Hormones and NTs
A: Nikolsky Sign
Dr. Banzuela II. CARRIER-MEDIATED TRANSPORT
✔GUIDE QUESTION Low concentration
The low-resistance pathways between myocardial cells that allow for the Osmosis → High • Water
spread of action potentials are the concentration
(A) gap junctions High concentration • GLUT transporters,
(B) T tubules Facilitated → Low
(C) sarcoplasmic reticulum (SR) • Amino Acid
Diffusion conconcentration
(D) intercalated disks transporters
(Passive; Downhill)
(E) mitochondria Costanzo LS. BRS Physiology. 6 ed. 2014. th

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TOPNOTCH MEDICAL BOARD PREP PHYSIOLOGY MAIN HANDOUT BY DR. ENRICO PAOLO C. BANZUELA
For inquiries visit www.topnotchboardprep.com.ph or https://www.facebook.com/topnotchmedicalboardprep/
This handout is only valid for October 2023 PLE batch. This will be rendered obsolete for the next batch since we update our handouts regularly.
TYPE MOVEMENT EXAMPLES ✔GUIDE QUESTIONS
• Na+-K+-ATPase Which of the following will double the permeability of a solute in a lipid
pump, bilayer?
(A) Doubling the molecular radius of the solute
• H+-K+ ATPase pump
(B) Doubling the oil/water partition coefficient of the solute
of the parietal cells (C) Doubling the thickness of the bilayer
(stomach), (D) Doubling the concentration difference of the solute across the
• H+-ATPase pump in bilayer 1-19 Costanzo LS. BRS Physiology. 7 ed. 2019.
th

Low concentration intercalated cells Solutions A and B are separated by a membrane that is permeable to
Primary
→ High (kidneys) urea. Solution A is 10 mM urea, and solution B is 5 mM urea. If the
Active
concentration • Ca2+-ATPase pump concentration of urea in solution A is doubled, the flux of urea across the
Transport membrane will
(Active; Uphill) in the cell
(A) double
membrane &
(B) triple
Sarcoplasmic (C) be unchanged
Reticulum (SR), (D) decrease to one-half
• multi-drug (E) decrease to one-third 1-11 Costanzo LS. BRS Physiology. 7 ed. 2019.
th

resistance
For the guide question above:
transporters J1 = PA (C1-C2) =PA (10-5) = 5
• SGLT-1 in the Small J2 = PA (C1-C2) = PA (20-5) = 15
intestines J2 is 3x more than J1. Kaya “triple” yung sagot.
• SGLT-2 in the Remember: flux of urea is from high concentration to low concentration
Proximal since urea undergoes simple diffusion.
Convoluted Tubules Dr. Banzuela

(PCT) SPECIAL NOTES: CARRIER-MEDIATED TRANSPORT


Low concentration • Important Characteristics:
Secondary • Na2+-K+-2Cl- in
→ High o Stereospecificity: Two substances may have the same chemical
Active Thick Ascending
concentration composition, but different “shape”. Carriers accommodate a
Transport Limb (TAL)
(Active; Uphill) specific “shape” (e.g., D-glucose vs. L-glucose)
of the Loop of Henle
(LH) o Saturation: number of carriers are finite. Once all carriers are
• Na-Ca2+ exchange in filled up or saturated, rate of transport becomes constant
almost all cells (Transport Maximum)
• Na+-H+ exchange in o Competition: different solutes may compete for same carrier
the PCT (kidneys) (e.g., Gal vs. Glu in the SGLT-1 of small intestine)
o SGLT-1 Deficiency in newborns lead to glu/gal malabsorption
SPECIAL NOTES: SIMPLE DIFFUSION leading to severe diarrhea
• Measured using the formula: Remember the properties of Carrier-Mediated Transport: S-S-C –
𝑱 = 𝑷𝑨 × (𝑪𝟏 − 𝑪𝟐 ) stereospecificity, saturation and competition. May shape lang na
pwedeng gumamit ng carrier protein (stereospecificity), limited ang
J = flux (flow (mmol/sec)
number ng carrier protein (saturation), at pwedeng magkaroon ng
P = permeability (cm/sec) competition for the carrier proteins (competition: parang “Trip to
A = area (cm2) Jerusalem”).
C1 = higher concentration 1 (mmol/L) Dr. Banzuela

C2 = lower concentration 2 (mmol/L) SPECIAL NOTES: FACILITATED DIFFUSION


• At low-solute concentrations: Facilitated Diffusion (FD) is faster
than Simple diffusion (SD) because FD involves carrier proteins,
which makes it go faster, analogous to a person riding a fast car
• At high-solute concentrations: Facilitated Diffusion is slower
than Simple Diffusion (because FD exhibits saturation and
transport maximum (basically a speed limit), unlike SD)
GLUT 1 Blood-brain barrier, RBCs, Cornea, Placenta
Liver, Pancreas (β islet cells), Basement Membrane
GLUT 2
of Small Intestine, Kidney
GLUT 3 Neurons, Placenta
Muscles, Adipose (only insulin-dependent glucose
GLUT 4
transporter)
For fructose transport from Small intestinal lumen
GLUT 5 to small intestinal cell cell, Spermatocytes (fructose
is the energy source for sperm motility)

© Topnotch Medical Board Prep

When we place formulas in the handout, it means they are important. Look
at the formula above. Memorize these formulas.
Dr. Banzuela
• P (permeability) in the formula J= PA (C1-C2) is increased by the
following:
o Increased Oil / water partition coefficient of solute (increases
solubility in the lipid of the membrane)
o Decreased Radius of solute
o Decreased Membrane Thickness
• Small Hydrophobic Solutes (O2, CO2): high permeability © Topnotch Medical Board Prep
• Hydrophilic Solutes (Na, K): uses aquaporins or transporters to
cross cell membrane GLUT TRANSPORTERS
• Most important characteristic of hydrophobic hormones that MNEMONIC
governs diffusion across cell membrane: Lipid Solubility https://qrs.ly/c4ebfzn
Take note of the formula for simple diffusion (J=PA(C1-C2), and the factors
that will increase permeability – increased oil/water partition coefficient
SPECIAL NOTES: PRIMARY ACTIVE TRANSPORT
of the solute, small size, thin membrane. You need that to answer the guide
question below: • Exhibits co-transport (“symport”) and Countertransport (“anti-
Dr. Banzuela port” or “exchange”)
• Source of energy: ATP hydrolysis
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For inquiries visit www.topnotchboardprep.com.ph or email us at [email protected]
This handout is only valid for October 2023 PLE batch. This will be rendered obsolete for the next batch since we update our handouts regularly.
TOPNOTCH MEDICAL BOARD PREP PHYSIOLOGY MAIN HANDOUT BY DR. ENRICO PAOLO C. BANZUELA
For inquiries visit www.topnotchboardprep.com.ph or https://www.facebook.com/topnotchmedicalboardprep/
This handout is only valid for October 2023 PLE batch. This will be rendered obsolete for the next batch since we update our handouts regularly.
• Na+-K+ ATPase Pump ✔ GUIDE QUESTIONS
o 3 Sodium Out, 2 Potassium In (Mnemonic: “TRI-NA TO-K-EN”) Which of the following characteristics is shared by simple and facilitated
o Keeps Na+ in the ECF and K+ in the ICF diffusion of glucose?
o Contributes to RMP (-4mv out of the -70mv) (A) Occurs down an electrochemical gradient
(B) Is saturable
o Contributes to Basal Metabolic Rate (BMR)
(C) Requires metabolic energy
o Some cardiac Na+-K+-ATPase pump inhibited by Digoxin (D) Is inhibited by the presence of galactose
o Found in the basement membrane side except for Choroid (E) Requires a Na+ gradient 1-1 Costanzo LS. BRS Physiology. 7 ed. 2019. th

Plexus
Movement is from high-concentration to low-concentration.
• Ca2+-ATPase pump in the sarcoplasmic reticulum: SERCA Remember: both simple and facilitated diffusion occurs down an
o SERCA pumps Ca2+ back to the SR electrochemical gradient!
o Uses primary active transport in the smooth endoplastic Dr. Banzuela

reticulum Transport of D- and L-glucose proceeds at the same rate down an


• H+-K+-ATPase pump in the lumen of the parietal cells of the electrochemical gradient by which of the following processes?
(A) Simple diffusion
stomach: Proton Pump (B) Facilitated diffusion
(C) Primary active transport
(D) Cotransport
(E) Countertransport 1-18 Costanzo LS. BRS Physiology. 7 ed. 2019. th

Glucose is supposed to be transported via carrier-mediated means.


Dapat may stereospecificity, so normally hindi same rate and transport
ng D-glucose at L-glucose. Pag same lang rate of transport ng D-glucose
and L-glucose, ibig sabihin hindi siya carrier-mediated – simple
diffusion na siya. Ingat, this is a tricky question since the transport of
D-glucose and L-glucose is not through simple diffusion in real life.
Dr. Banzuela
Which of the following would occur as a result of the inhibition of Na+,K+-
ATPase?
(A) Decreased intracellular Na+ concentration
© Topnotch Medical Board Prep
(B) Increased intracellular K+ concentration
Remember:” basta may ATP sa name, Primary yan.” (C) Increased intracellular Ca2+ concentration
Dr. Banzuela
(D) Increased Na+–glucose cotransport
SPECIAL NOTES: SECONDARY ACTIVE TRANSPORT (E) Increased Na+–Ca2+ exchange 1-23 Costanzo LS. BRS Physiology. 7 ed. 2019. th

• Exhibits co-transport (“symport”) and Countertransport (“anti-


If you inhibit the primary transport Na-K-ATPase pump, you will
port” or “exchange”) prevent Na+-gradient in the ECF from occurring. This would then
• Source of Energy: downhill transport of Na+ (indirectly relies on prevent all secondary active transport processes including the Na+-Ca2+
Na+-K+-ATPase pump) pump (a pump that causes Na+ influx and Ca2+ efflux). Less calcium
Remember:” basta may sodium sa name, Secondary yan.” then goes out, leading to increased intracellular calcium concentration.
Dr. Banzuela
A drug that inhibits Na+-K+-ATPase pump: think DIGOXIN.
• Co-Transport (Symport): solutes move in same direction Dr. Banzuela

• Countertransport (Antiport, Exchange): solutes move in Which of the following transport processes is involved if transport of
opposite directions glucose from the intestinal lumen into a small intestinal cell is
inhibited by abolishing the usual Na+ gradient across the cell
• Sodium-Glucose Cotransport (SGLT)
membrane?
o Na+ moves downhill, Glu moves uphill, both move in the same (A) Simple diffusion
direction (Cotransport) (B) Facilitated diffusion
o SGLT-1: SI, SGLT-2: Kidneys (C) Primary active transport
(D) Cotransport
(E) Countertransport 1-25 Costanzo LS. BRS Physiology. 7 ed. 2019. th

SGLT-1 is used to transport glucose from S.I. lumen to S.I. cells. It is a


secondary active transport utilizing co-transport-symport. Walang
Secondary active transport sa choices, so best answer is co-transport.
Dr. Banzuela
Adenosine triphosphate (ATP) is used indirectly for which of the
following processes?
(A) Accumulation of Ca2+ by the sarcoplasmic reticulum (SR)
(B) Transport of Na+ from intracellular to extracellular fluid
(C) Transport of K+ from extracellular to intracellular fluid
(D) Transport of H+ from parietal cells into the lumen of the stomach
(E) Absorption of glucose by intestinal epithelial cells
1-28 Costanzo LS. BRS Physiology. 7th ed. 2019

Because all secondary active transports (e.g. SGLT-1), relies on the Na+-
© Topnotch Medical Board Prep gradient created by the Na+-K+-ATPase pump.
Dr. Banzuela
Mnemonic: SGLT-1 is in the small intestines, SGLT-2 is in the kidneys. Think
A new drug is developed that blocks the transporter for H+ secretion in
of it this way: you have 1 Intestine, but you have 2 kidneys: SGLT-1 and
gastric parietal cells. Which of the following transport processes is
SGLT-2.
Dr. Banzuela being inhibited?
• Sodium-Calcium Countertransport (Na+-Ca2+ Exchange) (A) Simple diffusion
o Na+ moves downhill, Ca2+ moves uphill, they move in opposite (B) Facilitated diffusion
(C) Primary active transport
directions
(D) Cotransport
o Na+-Ca2+ exchange in the cardiac membrane: decreases (E) Countertransport 1-32 Costanzo LS. BRS Physiology. 7 ed. 2019 th

intracellular Ca2+
H+-K+-ATPase pump is the proper term for the proton pump of the
o MOA of Digoxin: inhibits cardiac Na+-K+-ATPase Pump →
parietal cells of the stomach. It is a Primary Active Transport,
inhibits Na+-Ca2+ pump → greater intracellular calcium → countertransport.
GREATER CARDIAC CONTRACTILITY Dr. Banzuela

§ Hypokalemia increases the risk and severity of digitalis


toxicity because: hyperpolarized cardiac membrane → 1.3 OSMOSIS
further increased inhibition of the Na-K-ATPase pump
OSMOLARITY
• Concentration of osmotically active particles in a solution
• Measured in Osmoles/Liter
• “Pogi” points of water
o The higher the osmolarity of a solution, the more it attracts
water from an opposite compartment
𝑂𝑠𝑚𝑜𝑙𝑎𝑟𝑖𝑡𝑦 = 𝐶𝑜𝑛𝑐𝑒𝑛𝑡𝑟𝑎𝑡𝑖𝑜𝑛 × # 𝑜𝑓 𝐷𝑖𝑠𝑠𝑜𝑐𝑖𝑎𝑏𝑙𝑒 𝑃𝑎𝑟𝑡𝑖𝑐𝑙𝑒𝑠
𝑚𝑂𝑠𝑚/𝐿 = 𝑚𝑚𝑜𝑙/𝐿 × 𝑁𝑢𝑚𝑏𝑒𝑟 𝑜𝑓𝑝𝑎𝑟𝑡𝑖𝑐𝑙𝑒𝑠/𝑚𝑜𝑙
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For inquiries visit www.topnotchboardprep.com.ph or email us at [email protected]
This handout is only valid for October 2023 PLE batch. This will be rendered obsolete for the next batch since we update our handouts regularly.
TOPNOTCH MEDICAL BOARD PREP PHYSIOLOGY MAIN HANDOUT BY DR. ENRICO PAOLO C. BANZUELA
For inquiries visit www.topnotchboardprep.com.ph or https://www.facebook.com/topnotchmedicalboardprep/
This handout is only valid for October 2023 PLE batch. This will be rendered obsolete for the next batch since we update our handouts regularly.
• Normal ECF Osmolarity: 300 mOsm/L REFLECTION COEFFICIENT /OSMOTIC COEFFICIENT (RC)
• Normal ICF Osmolarity: 300 mOsm/L • Number between zero and one
Normal values differ depending on the textbook that you are going to use • Describes ease by which solute permeates a membrane
– so do not obsess about it, at alam din yan ng examiners – they rarely ask RC DESCRIPTION EXAMPLE NOTES
you what the normal value of this or that is. In some books, ECF and ICF
No solute Effective Osmole
osmolarity is 285, in other books it’s 310. The values here reflect commonly One Albumin
accepted normal values by physiology teachers in the Philippines.
penetration (creates Osm P)
Dr. Banzuela
Between
• *ECF and ICF are Isoosmotic relative to each other! Some solute Most
Zero and -
• Substance with an osmolarity/osmolality of zero: Water penetration substances
One
• Movement of water across a semipermeable membrane from a solution Complete Ineffective
with low solute concentration to a solution with high solute concentration Zero solute Urea Osmole
Remember: water utilizes OSMOSIS and not simple diffusion. Water will penetration (No osmotic effect)
move according to CONCENTRATION GRADIENT (concentration
differences between two compartments) and not according to volume
differences between two compartments. Water will move from LOW
CONCENTRATION (“dilute” compartment) to HIGH-CONCENTRATION
(“concentrated” compartment). Do not confuse water movement (osmosis)
with solute movement using simple diffusion.
Main electrolyte that maintains the cell gradient - Na, K, Cl, Mg?
A: Na (“where sodium goes, water follows”)
Dr. Banzuela

• Driving Force: Osmotic Pressure


o Osmotic Pressure computed using van’t Hoff Law

REFLECTION COEFFICIENT (σ)


© Topnotch Medical Board Prep

Look at the pic above. Wag matakot sa RC. Think of RC as a formula:


© Topnotch Medical Board Prep RC = amount “returned”/amount “sent”
𝝅 = 𝒈 × 𝑪 × 𝑹𝑻 Albumin has an RC of one – meaning if 8 molecules of Albumin try to
where: penetrate the membrane, none will be able to do so. 8 “sent”, 8 “returned”.
π = Osmotic pressure (atm or mm Hg) RC = 8/8 = 1. Albumin has an RC of 1. It’s an effective osmole and attracts
g = Number of particles per mole in solution (Osm/mol) water to where it is concentrated.
C = Concentration (mmol/L) Urea has an RC of 0. If 8 molecules of urea try to penetrate the membrane,
8 molecules (all molecules) will penetrate. RC = 0/8 = 0. Urea has RC of
R = Gas constant (0.082 L − atm/mol − K) zero. It’s an ineffective osmole and cannot easily attract water.
T = Absolute temperature (K) Dr. Banzuela
EFFECTIVE OSMOTIC PRESSURE Example of good analysis questions: Compartments A and B has same
• Effective Osmotic Pressure = Osmotic Pressure x Reflection Coefficient amount of K+ and Cl- which are impermeable to the membrane. Solutes in
• Same effective osmotic pressure: Isotonic compartment B went to Compartment A. Which one has higher osmolarity
• Higher effective osmotic pressure: Hypertonic pressure? A: Compartment B
Dr. Banzuela
• Lower effective osmotic pressure: Hypotonic
• Rule: water undergoes osmosis from hypotonic solution to ✔ GUIDE QUESTIONS
hypertonic solution In a hospital error, a 60-year-old woman is infused with large volumes of
a solution that causes lysis of her red blood cells (RBCs). The solution
• Osmotic pressure exerted by proteins: Oncotic Pressure or
was most likely:
Colloid Osmotic Pressure (A) 150 mM NaCl
Remember that proteins can exert osmotic pressure, it can attract water. (B) 300 mM mannitol
This is the basis for ONCOTIC pressure – something that you will read again (C) 350 mM mannitol
and again in this handout. (D) 300 mM urea
What happens when you give isotonic fluid to a patient: Blood pressure (E) 150 mM CaCl2 1-9 Costanzo LS. BRS Physiology. 7 ed. 2019 th

increases, hematocrit decreases, Plasma protein concentration


A and B are isotonic compared to the RBC ICF (yung A, kaya isotonic,
decreases, ECF osmolarity is still 300mOsm/L
Dr. Banzuela remember na magseseparate yung Na and Cl, kaya and actual effective
osmotic pressure nyan ay 150 x 2 = 300. C and E are hypertonic (C is
hypertonic dahil 150 x 3 naman). D is hypotonic – not because of the
RBC AND OSMOSIS concentration na 300, but because ang RC niya is less than 1 (ineffective
osmole siya, so ang effective osmotic pressure niya is actually less than
https://qrs.ly/7pebg0z
300). Because D is hypotonic, water will move from ECF to ICF causing
cellular swelling, and eventually, cellular rupture.
Dr. Banzuela
Refer to this audio file as you look at the picture below. Solutions A and B are separated by a semi-permeable membrane.
Dr. Banzuela
Solution A contains 1 mM sucrose and 1 mM urea. Solution B contains
1 mM sucrose. The reflection coefficient for sucrose is one and the
reflection coefficient for urea is zero. Which of the following
statements about these solutions is correct?
(A) Solution A has a higher effective osmotic pressure than solution B
(B) Solution A has a lower effective osmotic pressure than solution B
(C) Solutions A and B are isosmotic
(D) Solution A is hyperosmotic with respect to solution B, and the
solutions are isotonic
(E) Solution A is hypoosmotic with respect to solution B, and the
solutions are isotonic
1-17 Costanzo LS. BRS Physiology. 7th ed. 2019

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TOPNOTCH MEDICAL BOARD PREP PHYSIOLOGY MAIN HANDOUT BY DR. ENRICO PAOLO C. BANZUELA
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Iba ang osmotic pressure sa effective osmotic pressure (see these ✔GUIDE QUESTION
formulas in the previous discussion). Urea osmotic pressure is 1mM. Solutions A and B are separated by a semipermeable membrane that is
Pero yung effective osmotic pressure niya is zero. So, solution A is permeable to K+, but not to Cl–. Solution A is 100 mM KCl, and solution
hyperosmotic but same lang ang tonicity sa solution B (since ang terms B is 1 mM KCl. Which of the following statements about solution A and
na “isotonic”, “hypertonic” and “hypotonic” refer to effective osmotic solution B is true?
pressure and not just osmotic pressure) (A) K+ ions will diffuse from solution A to solution B until the [K+] of both
Dr. Banzuela
solutions is 50.5 mM
Assuming complete dissociation of all solutes, which of the following (B) K+ ions will diffuse from solution B to solution A until the [K+] of both
solutions would be hyperosmotic to 1 mM NaCl? solutions is 50.5 mM
(A) 1 mM glucose (C) KCl will diffuse from solution A to solution B until the [KCl] of both
(B) 1.5 mM glucose solutions is 50.5 mM
(C) 1 mM CaCl2 (D) K+ will diffuse from solution A to solution B until a membrane
(D) 1 mM sucrose potential develops with solution A negative with respect to solution
(E) 1 mM KCl From Physiology BRS, 6 Ed th
B
1mM x 3 kasi ang C. (E) K+ will diffuse from solution A to solution B until a membrane
Dr. Banzuela
potential develops with solution A positive with respect to solution B
1-3 Costanzo LS. BRS Physiology. 7th ed. 2019

1.4 DIFFUSION POTENTIAL, RESTING MEMBRANE K+ is positively charged. It will move from Solution A to B (high
concentration to low concentration). Solution A will now become
POTENTIAL, ACTION POTENTIAL negative compared to Solution B.
ION CHANNELS Dr. Banzuela

• Cell membrane integral proteins that permit passage of certain RESTING MEMBRANE POTENTIAL
ions • Exhibited by all cells
o Selective for specific ions • By convention, refers to intracellular charge
o Maybe open or closed • Established by diffusion potentials resulting from concentration
Characteristics of ion channels selectivity based on distribution of charges differences of various ions as each attempt to drive the
and size of channels. Small channel lined with negatively charged groups membrane potential towards its equilibrium potential
will exclude large solutes for example • Normal Nerve RMP: -70mV
Dr. Banzuela
o Caused by:
VOLTAGE-GATED LIGAND-GATED § Nernst Potential for Na+ and K+
CHANNELS CHANNELS § K+ Leak Channels
Opened or closed § Na+-K+-ATPase Pump
Opened or closed by
by changes in o Closer to EK+ −85mV ENa+ +65mV
Mechanism hormones, 2nd
membrane § Nerve membrane more permeable to K+ than Na+ (high
messengers, NTs
potential resting conductance to K)
Skeletal Muscle AChR (NM • Causes reduction of potassium leak out of the cells:
Activation vs.
Receptor) that opens gate Hyperpolarizing the membrane potential
Examples Inactivation gate of
for Na+ and K+ when Ach
nerve Na+ channel
binds ACTION POTENTIAL (AP)
Don’t be afraid of the term “ligand”. Ligand means “messenger.” That • Exhibited only by excitable cells (neurons, all muscle types)
messenger can either be hormones or neurotransmitters.
Dr. Banzuela
• Consists of rapid depolarization/upstroke (“on”) followed by
repolarization (“off”)
DIFFUSION POTENTIAL AND EQUILIBRIUM POTENTIAL • Characteristics of a True Action Potential:
• Diffusion Potential 1. Stereotypical size and shape: each normal AP for a given cell
o Potential difference generated across a membrane because of type looks identical, depolarizes to the same potential and
a concentration difference of an ion repolarizes to the same RMP
• Equilibrium Potential (Nernst Potential) 2. Propagating: AP at one cell causes depolarization of adjacent
o Diffusion potential that exactly balances (opposes) the tendency cells in a nondecremental manner
for diffusion caused by concentration difference 3. All-or-none: if threshold is reached, a full-sized AP will be
o At electrochemical equilibrium, chemical and electrical driving produced, otherwise, none at all
forces that act on an ion are equal and opposite; no net diffusion Remember: all cells have a Resting Membrane Potential. But only excitable
occurs cells have an Action Potential. These excitable cells are neurons, skeletal
o Calculated by Nernst Equation: muscle, cardiac muscles, and smooth muscles.
In terms of action potential – remember the 3 characteristics –
Stereotypical size and shape (meaning if I graph it, I will get the same thing
again and again), propagation (kumakalat – pag nag AP ang isang cell,
magkakaroon ng AP yung next cell) and all-or-none (“on” or “off” state. It
will be in the “on” state once threshold is reached.
Dr. Banzuela
NERVE ACTION POTENTIAL
• Depolarization
o Opening of Na-Activation Gate (m gate) → Na inward current
• Repolarization
o Closure of Na-Inactivation Gate (h gate) → stop Na inward
o Equilibrium Potentials in Nerve and Muscle: current
o ENa+ = +65mV, ECa2+ = +120mV, EK+ = -85mV, ECl- = -85mV o Opening of K gates → K outward current
Depolarization – net inward current, cell interior becomes less negative
(you turn it “on”). Repolarization – you make the cell more negative (you
turn it “off”). Look at the Na+-Channels and the K+-channels of an excitable
cell like neurons above. The Na channels has two gates similar to an
anteroom/waiting room. These two gates are the Na-activation and Na-
inactivation gates. At rest, the Na-activation gates (m gate) is closed, while
the Na-inactivation gates (h gate) is open. K-channels have just one gate.
When you have depolarization, the Na-activation gates open. And since Na
concentration is greater in the ECF compared to the ICF, Na influx will
occur, causing the cell to become more positive.
In repolarization, Na+-inactivation gates close (preventing Na+-influx) and
K gates open (causing positive charges to leave the cell, making the cell
more negative).
Dr. Banzuela

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TERM DESCRIPTION
• Occurs during an AP after ARP when a
Relative Refractory new AP can be elicited by required
Period (RRP) greater than usual Na+ inward current
• Basis: prolonged opening of K+ channels
• Occurs when cell membrane is
depolarized but not rapidly enough,
Accommodation thus causing Na-inactivation gates
to eventually close → no AP
• e.g. Hyperkalemia
• non-propagated local potential
Electrotonic potential due to local change in ionic
conductance
• local electrical charge in the
Generator potential / generator / sensitive region of the
Synaptic Potential receptor cell
• graded potential
• principal inputs signals to which a
neuron responds
Synaptic potentials
• conductance changes are triggered
by neurotransmitters
✔GUIDE QUESTIONS
During the upstroke of the nerve action potential
(A) there is net outward current and the cell interior becomes more
negative
(B) there is net outward current and the cell interior becomes less
negative
(C) there is net inward current and the cell interior becomes more
negative
(D) there is net inward current and the cell interior becomes less
negative
1-2 Costanzo LS. BRS Physiology. 7th ed. 2019
A newly developed local anesthetic blocks Na+ channels in nerves.
Which of the following effects on the action potential would it be
expected to produce?
(A) Decrease the rate of rise of the upstroke of the action
potential
© Topnotch Medical Board Prep (B) Shorten the absolute refractory period
(C) Abolish the hyperpolarizing afterpotential
(D) Increase the Na+ equilibrium potential
(E) Decrease the Na+ equilibrium potential
1-20 Costanzo LS. BRS Physiology. 7th ed. 2019

Lidocaine blocks neuronal voltage-gated sodium channels responsible for


action potential generation and propagation. It can also act on cardiac
muscles and cause arrhythmias.
Dr. Banzuela
PROPAGATION OF ACTION POTENTIAL (AP)
• Done through local currents to adjacent areas of the membrane
• Conduction velocity is increased by:
o Fiber Size: the larger the nerve fiber, the smaller the internal
resistance, and the faster the conduction velocity
o Conduction velocity is most dependent on: nerve diameter
o Myelination: myelin acts as insulator. AP is regenerated in
Nodes of Ranvier (unmyelinated portions of the axon) that
contains the highest concentration of Na+ channels per
square micrometer of cell membrane
• Conduction Velocity = Distance/Latent Period

© Topnotch Medical Board Prep ACTION POTENTIAL CONDUCTION VELOCITY IS ENHANCED


SPECIAL NOTES: ACTION POTENTIAL BY:
TERM DESCRIPTION Rapid gating allows for rapid action
Rapid Na+
Depolarization • Make the MP more positive potential upstroke, which speeds
Channel Gating
Hyperpolarization • Make the MP more negative conduction
• Positive charges flow into the cell Wider axons have lower resistance,
Inward Current Wide Axons allowing electrical signals to travel farther
causing depolarization
• Positive charges flow out of the cell without much amplification
Outward Current Myelin allows electrical insulation,
causing hyperpolarization
• MP where AP is inevitable Myelination reducing leak currents that short circuit
o net inward current > net the signal
Threshold outward current AP jumps electronically from node to
Saltatory
o Na+ inward current > K+ outward node, reducing the need for slower active
Conduction
current from K leak channels regeneration steps
• Occurs during an AP when MP > Remember: the thicker the nerve, the faster it is. The more myelinated the
Overshoot
0mV nerve, the faster it is. Myelin is an insulator, not a conductor, produced by
Undershoot • Occurs during an AP when MP < Schwann Cells (in the peripheral nervous system or PNS) and
Oligodendrocytes (in the central nervous system or CNS). AP is
(After-hyperpolarization) RMP
REGENERATED in each Node of Ranvier – this ensures that no matter how
• Occurs during an AP when no new far you are from the initial segment/axon hillock (where AP is first
Absolute Refractory AP can be elicited no matter how generated), the strength of the signal is maintained, since regenerated
Period (ARP) large the stimulus yung AP in each Node of Ranvier.
• Basis: closed Na+-inactivation gates Dr. Banzuela

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✔GUIDE QUESTION
The velocity of conduction of action potentials along a nerve will be
increased by __________.
(A) stimulating the Na+–K+ pump
(B) inhibiting the Na+–K+ pump
(C) decreasing the diameter of the nerve
(D) myelinating the nerve
(E) lengthening the nerve fiber 1-16 Costanzo LS. BRS Physiology. 7 ed. 2019th

1.5 NEUROMUSCULAR AND SYNAPTIC


TRANSMISSION
SUPPORTING CELLS OF THE NERVOUS SYSTEM
(NON-NEURONS)
CHARACTERISTICS CELL
A tissue macrophage that acts as
scavenger cells, removing debris
resulting from injury, infection, and
MICROGLIA
disease (e.g., multiple sclerosis,
AIDS-related dementia, Parkinson © Topnotch Medical Board Prep

disease, & Alzheimer disease) • Terminal Boutons (End-Feet): distal tips of the axon
Macroglia that forms myelin in the OLIGODENDROCYTES • Voltage-Gated Calcium Channels (VGCC): stimulated by AP;
CNS and PNS respectively & SCHWANN CELLS triggers release of NT into the synapse
Helps in regeneration and o LAMBERT-EATON MYASTHENIC SYNDROME: autoimmune
SCHWANN CELLS
remyelination in the PNS disease marked by auto-antibodies against these voltage-gated
Macroglia that send processes that calcium channels → prevents Acetylcholine from being released
envelop synapses and the surface of ASTROCYTES to the neuromuscular junction
nerve cells, and helps form the BBB • Synapse: space between neurons
Astrocytes in the white matter FIBROUS ASTROCYTES o Mechanism for the release of neurotransmitters in the synapse:
Astrocytes in gray matter, with Exocytosis
granular cytoplasm and produce • Neurotrasmitters: either excitatory (depolarizes) or inhibitory
substances that are tropic to (hyperpolarizes); binds to post-synaptic receptors
PROTOPLASMIC
neurons to help maintain
ASTROCYTES CLINICAL CORRELATES MULTIPLE SCLEROSIS
appropriate concentration of ions
and NTs by taking up K+ and the NTs • Multiple Sclerosis (MS): autoimmune disease directed
Glutamate and GABA against the components of the myelin sheath
o Brain MRI and CSF analysis (presence of oligoclonal
PARTS OF THE NEURON bands): used to diagnose MS
• Associated with HLA-DR2
• Clinical Presentation: Distinct episodes of neurologic
deficits that are separated in time, and are attributable to
patchy white matter lesions that are separate in space
• Paraparesis (weakness in lower extremities), paresthesia,
optic neuritis (blurred vision, change in color perception,
central scotoma, pain in eye movements)
• Relapsing-Remitting MS: transient episodes lasting weeks or
months that recur
• Primary-Progressive MS: no periods of remission
4-8. Barrett et al. Ganong’s Review of Medical Physiology. 26th ed. 2019

SYNAPTIC TRANSMISSION
• Synaptic Transmission is Orthodromic (Synapse to Axon) rather
than Antidromic (Axon to Synapse)
one neuron, one post-synaptic
PARTS OF A One-to-one synapses element (e.g., neuromuscular
NEURON junctions or NMJ)
https://qrs.ly/rlebg1y Many neurons, one post-synaptic
Many-to-one synapses
Refer to this audio file as element (e.g., spinal motor neurons)
you look at this picture. depolarizes postsynaptic cell,
Excitatory Post-Synaptic
Dr. Banzuela
brings it closer to threshold (e.g.,
Potentials (EPSPs)
due to Na+ influx)
Inhibitory Post-Synaptic hyperpolarizes postsynaptic cells
Potentials (IPSPs) (e.g., due to Cl- influx)
2 or more excitatory inputs at the
Spatial Summation
same time (A + B + C)
2 or more excitatory inputs at
Temporal summation
rapid succession (A…A…A…)
Facilitation /
Augmentation / brings cell closer to threshold
© Topnotch Medical Board Prep Postetanic Stimulation
• Dendrites: where neurotransmitter (NT) receptors are found
• Cell Body (Soma): where organelles, nucleus is seen SYNAPTIC TRANSMISSION
PHENOMENON CAUSED BY
Speaking of nucleus – the nucleus of the cell is the one that controls and
regulates cellular activities since it is the one that carries the genes that is
Endplate Potential Increase in Na+ Conductance (Na+
used in the production of cellular proteins like enzymes. (in skeletal muscle motor
endplate)
Influx)
Dr. Banzuela

• Initial Segment: where AP starts Can be caused by opening of Cl-


Fast Inhibitory Post-
• Axon: transmitting portion Channels (Cl- Influx), opening of K+
Synaptic Potential
• Nodes of Ranvier: unmyelinated portion of the axon channels (K+ efflux), or closure of
(IPSP)
• Neural Fibril: branches of the axon Na+ or Ca2+ channels

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This handout is only valid for October 2023 PLE batch. This will be rendered obsolete for the next batch since we update our handouts regularly.
PHENOMENON CAUSED BY CHARACTERISTICS NEUROTRANSMITTER
Fast Excitatory Post- Increase in Na+ Conductance (Na+ • Secreted in the substantia nigra
Synaptic Potential (Fast Influx) or Ca2+ Conductance (Ca2+ (fine-tunes movement)
EPSP) influx) • Also secreted by the hypothalamus
Slow Excitatory Post- (Prolactin-Inhibiting Factor or PIF)
Decrease in K+ Conductance (Slow K+
Synaptic Potential to inhibit prolactin;
efflux)
(Slow EPSP) • D1 Receptor: activates adenylate
Opening of voltage-gated K+ channels cyclase using Gs protein; D2: inhibits
Presynaptic Inhibition DOPAMINE
(K+ Efflux) adenylate cyclase using Gi protein;
Adapted from 6-1, 6-7, 6-8. Barrett et al. Ganong’s Review of Medical Physiology. 26th ed. 2019
• ↓ in Parkinson Disease, ↑ D2 in
Schizophrenia
✔GUIDE QUESTION
o Schizophrenia: can be due to
An inhibitory postsynaptic potential:
(A) depolarizes the postsynaptic membrane by opening Na+ channels abnormalities in the prefrontal
(B) depolarizes the postsynaptic membrane by opening K+ channels lobes, frontal lobes and limbic
(C) hyperpolarizes the postsynaptic membrane by opening Ca2+ system (hippocampus)
channels • Found in the median raphe of the
(D) hyperpolarizes the postsynaptic membrane by opening brain stem, from tryptophan,
Cl- channels SEROTONIN
1-22 Costanzo LS. BRS Physiology. 7 ed. 2019 th
converted to melatonin;
Remember – you can inhibit an AP several ways – cause influx, or Cl- • low levels association with depression
cause K+ efflux or inhibit Na+ influx/Ca2+ influx. All of these will make • NO synthase converts Arginine to
the cell more negative/less positive. citrulline and NO;
Dr. Banzuela
• Classification: Inhibitory non- NITRIC OXIDE (NO)
NEUROTRANSMITTERS (NTS) adrenergic, non-cholinergic
• Function of NTs: Chemical messengers • Permeant gas, inhibitory NT, vasodilator
• For communication between neurons Let me reiterate important points about the neurotransmitter table above:
• Maybe excitatory or inhibitory or both Ach is found in a variety of areas. It is unique among neurotransmitters in
that it is degraded before “reuptake” (process of recovering the
• Categories:
neurotransmitter by the releasing neuron) takes place. Usually, reuptake
o Small-Molecule NTs muna before degradation nangyayari.
§ Monoamines: e.g. Ach, Serotonin, Histamine
Plant used for depression (effectiveness is questioned); contraindicated in
§ Catecholamines: Dopamine, NE, Epi
pregnant patients: St. John's Wort
§ Amino Acids: Glutamate, GABA, Glycine For NE – remember that is the main secretion of post-ganglionic
o Large-Molecule NTs sympathetic neurons (compared to the adrenal medulla which secretes
§ Neuropeptides including substance P, enkephalin, mainly EPI and not NE).
vasopressin, and a host of others Epi has greater Beta-2 effect than NE, kaya siya ginagamit for asthma at
hindi NE.
NEUROTRANSMITTERS Dopamine – remember na iba yung substantia nigra dopamine (modulates
CHARACTERISTICS NEUROTRANSMITTER movement) at yung hypothalamic dopamine (inhibits prolactin).
Serotonin is the “happy hormone” – pag mababa siya, it’s associated with
• Maybe excitatory or inhibitory depression (serotonin rich food: chocolate! J).
• Found in the NMJ, Sympa and Para Nitric Oxide – remember its formula is NO and not N2O. N2O is nitrous oxide
Preganglionic neurons, Para and or laughing gas. NO is an INHIBITORY NT and a VASODILATOR. Again, NO
some Sympa Post-ganglionic is an INHIBITORY NT and a VASODILATOR – do not forget these please.
neurons, basal ganglia, large Diseases involving DOPAMINE: Parkinson Disease (decreased dopamine)
pyramidal cells of the motor cortex, and Schizophrenia (increased dopamine)
gigantocellular neurons of the REA Diseases involving ACETYLCHOLINE: Alzheimer Disease (decreased
acetylcholine) and Myasthenia Gravis (autoantibodies against Ach receptors)
• Created by: Choline Acetyl- Dr. Banzuela
transferase from Acetyl CoA and
✔GUIDE QUESTION
Choline Degeneration of dopaminergic neurons has been implicated in:
ACETYLCHOLINE
• Degraded by: Acetylcholinesterase (A) Schizophrenia (C) Myasthenia gravis
(ACH)
into Acetate and Choline (½ of which (B) Parkinson disease (D) Curare poisoning
will undergo reuptake) 1-30 Costanzo LS. BRS Physiology. 7th ed. 2019

• Neurotransmitter that opens Na-K Parkinson Disease:


pump that depolarizes the muscle • Mechanism: degeneration of dopaminergic neurons
end-plate to a value half way • Location involved: substantia nigra pars compacta
between Na K equilibrium • NT affected: Dopamine (decreased)
potentials Dr. Banzuela

• Triggers REM sleep


• decreased levels in Huntington
dementia and Alzheimer dementia NEUROTRANSMITTERS
• Found in the locus coeruleus of pons, https://qrs.ly/61ebg2a
• NeuroMODULATOR in the CNS and
NeuroTRANSMITTER in the PNS
Refer to this audio file for a summary of the table below along with some
• synthesized INSIDE synaptic vesicles mnemonics
• HALF-LIFE: 2 MINUTES (short Dr. Banzuela
NOREPINEPHRINE
compared to renin, aldosterone, CHARACTERISTICS NEUROTRANSMITTER
(NE)
corticosterone, and DHEA) • Spinal cord main inhibitory NT
• Primary neurotransmitter from the GLYCINE
• increases Cl influx
post-ganglionic sympathetic • Brain main inhibitory NT (e.g., spiny
neurons neurons of the striatum, Purkinje Cells
• For arousal/ wakefulness of the cerebellum)
• Secreted mainly by the adrenal • increases Cl- influx (GABAA) or K+
medulla Efflux (GABAB)
• greater Beta-2 action than NE • decreases anxiety: GABAA GABA
EPINEPHRINE (EPI) • GABA Receptors in the Retina
• Relieve effects of bee sting by
decreasing contraction of airway o GABA A: ionotropic; ubiquitous
smooth muscles o GABA B: metabotropic
o GABA C: ionotropic; enriched in the retina
compared to other parts of the CNS

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CHARACTERISTICS NEUROTRANSMITTER CHARACTERISTICS NEUROTRANSMITTER
• Brain main excitatory NT; • Inhibits neurons in the brain involved
• formed from reactive amination of in pain perception (e.g., enkephalin,
Alpha-ketoglutarate endorphins, dynorphins; does NOT OPIOID PEPTIDE
• 3 Receptor subtypes Ionotropic include morphine which is
GLUTAMATE
(ligand-gated) including NMDA exogenous)
receptors; GLUTAMATE &
• Involved in Fast Pain and Slow Pain
• 1 subtype metabotropic SUBSTANCE P
• Activates NMDA receptors
MNEMONICS: NEUROTRANSMITTERS
“Ilocus Norte” ”Pare True Love Does Not Exist To Me” “Trip Mo Sya Noh?”
locus coeruleus, NE Phenylalanine Derivatives Tryptophan Derivatives: melatonin, serotonin, niacin

© Topnotch Medical Board Prep

✔GUIDE QUESTION 1.6 SKELETAL MUSCLES


Which of the following is an inhibitory neurotransmitter in the central
nervous system (CNS)?
(A) Norepinephrine
(B) Glutamate
MUSCLE TYPES
(C) g -Aminobutyric acid (GABA) https://qrs.ly/4uebg2x
(D) Serotonin
(E) Histamine From BRS Physiology, 6th Ed
Watch this video on the various muscle types as you read the next portion.
Acts on inhibitory neurons through competitive antagonism of glycine Dr. Banzuela
receptors in the spinal cord, brain stem, and higher centers: Strychnine TYPES OF MUSCLES
Dr. Banzuela
NEUROTRANSMITTER RECEPTORS • Skeletal Muscles
• Metabotropic Receptors o Intrafusal: detects changes in Muscle Length (innervation:
o G-protein Coupled Receptors (GPCR) that utilizes second gamma-motorneurons)
messengers like IP3/DAG or cAMP o Extrafusal: for voluntary muscle contraction (innervation:
o e.g., GABAB receptor, Neurokinin receptor, Opioid Receptors alpha-motorneurons), has 2 types:
• Ionotropic Receptors PARAMETER TYPE I TYPE II
o Ion-channel linked-receptors that utilizes ligand-gated ion channels Contraction velocity Slow Fast
Fiber color Red White
o e.g., GABAA Receptor (Cl-), Nicotinic Receptor (Na+, K+), NMDA
Oxidative
Receptor (Ca2+), Glycine Receptor (Cl-), ANP receptor, 5HT3 receptor Predominant
phosphorylation → Anaerobic glycolysis
metabolism
OPIOID PEPTIDE RECEPTORS sustained contraction
• Come in 3 types: Mitochondria,
↑ ↓
o Kappa: analgesia, diuresis, sedation, meiosis, dysphoria myoglobin
Weight/resistance
o Mu: site of action of morphine, causes analgesia, respiratory Type of training Endurance training
training, Sprinting
depression, constipation, euphoria, sedation, meiosis, increased
GH and prolactin Think of “1 slow, red ox with a perfect posture.” Type I fibers are slow,
o Delta: analgesia red fibers using oxidative phosphorylation to allow sustained contraction
in endurance training. Postural muscles of the back have greater
• Affinity of opioid peptides shown below:
percentage of Type I fiber since they require endurance more than power.
o Mu: Endorphins > Enkephalins > Dynorphin
o Kappa: Enk > End and Dy Take note, the type of muscle fiber not used by sedentary person is your
TYPE 2 MUSCLE FIBER (WHITE MUSCLE FIBER, FAST-TWITCH)
o Delta: Dyn > End and Enk Dr. Rubio & Dr. Banzuela

This is based on Ganong 25th ed → iba yung nakasulat sa Ganong 23rd ed. • Cardiac Muscles
Iba rin nakasulat sa Katzung Pharma. o Atrial muscle: (+) gap junctions, (+) syncytium
Dr. Banzuela
o Ventricular muscle: (+) gap junctions, (+) syncytium
FUNCTION OF MUSCLES
o Pacemakers (e.g., SA Node): (+) autorhythmicity
1. Mobility, Stability & Posture
• Smooth Muscle
2. Circulation (e.g., pumping action of blood by cardiac muscles, o Unitary smooth muscle: (+) gap junctions, (+) syncytium, for
maintenance of BP by smooth muscles in the vessels)
gross motor movements
3. Respiration (e.g., via diaphragm) o Multi-unit smooth muscle: (-) gap junctions, for fine motor movements
4. Digestion
5. Urination SARCOMERE
6. Childbirth • Functional and structural unit of a muscle of skeletal and cardiac
7. Vision (e.g., intraocular and extraocular muscles) muscles
8. Organ protection (e.g., anterior abdominal wall muscles) • Area between two Z lines
9. Temperature regulation (85% of body heat comes from “Nooks and crannies.” Remember that sarcomere is the contractile unit of
contracting muscles) BOTH skeletal and cardiac muscle.
Largest Muscle: Gluteus Maximus. Strongest muscle by weight: masseter Majority of muscle weight comes from where? myosin, troponin, actin,
in the jaw. tropomyosin? Answer: Myosin
Dr. Banzuela Dr. Banzuela

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THICK FILAMENTS THIN FILAMENTS


• Thin Filament: contains actin, tropomyosin, troponin
• Thick Filament: contains myosin that act as cross-bridges of the
• Tropomyosin: “relaxing protein” that covers actin binding sites at rest
sarcomeres
• Troponin has 3 subunits: Troponin T, Troponin I, Troponin C
o 1 pair of heavy chains, two pairs of light chains
o Troponin T: attaches troponin complex to tropomyosin
o 2 heads, 1 tail
o Troponin I: inhibits actin-myosin binding
o Troponin C: calcium binding protein

© Topnotch Medical Board Prep © Topnotch Medical Board Prep

Troponin T-I-C.
T for tropomyosin (Troponin T is found in tropomyosin)
I for inhibition (Troponin I inhibits actin-myosin interaction)
C for calcium (Troponin C is the one that binds with calcium)
Components of thin filament of skeletal and cardiac muscle are Actin, Tropomyosin, Troponin. Hindi lang actin, okay? =)
Dr. Banzuela

• Z lines (“Zwischenscheibe”): borders


• M line (“Mittelscheibe”): midline
• A Band (”Anisotropic”): entire length of
myosin
• H Band (”Heller”): inside A band; purely
myosin, no actin interspersed
• Bare Zone: inside H band; no myosin heads
• I band (“Isotropic): purely actin, no myosin
interspersed
The H-band is the area inside the A-band without
actin filaments. The area in the H-band containing
pure myosin (no myosin heads) is the bare zone.
© Topnotch Medical Board Prep Dr. Banzuela

• Trasnsverse tubules or T-Tubules :


invaginations of the sarcolemma; spreads the
action potential to all parts of the muscles;
contains DHPR
• DHPR: voltage-sensitive, activates
Ryanodine Receptors
• Sarcoplasmic Reticulum (SR): contains Ca2+
needed for muscle contraction
o Amount of calcium released by the SR
depends on amount of stored calcium
• Ryanodine: Ca2+-release channel in the SR
activated by DHPR
• Calsequestrin: protein that stores Ca2+ in the
SR
• SERCA: pumps Ca2+ from ICF to the SR
• Titin: binds myosin to Z lines, binds Z lines to
© Topnotch Medical Board Prep
M line (determines normal stiffness of the
ventricular muscle)
Titin mutations are associated with tibial muscular dystrophy, hypertrophic cardiomyopathy, familial dilated cardiomyopathy, limb-girdle muscular dystrophy
type 2J, centronuclear myopathy, core myopathy with heart disease and fatal cardiomyopathy. These mutations can cause premature stop codons and other
defects. In scleroderma, autoantibodies to titin are also produced.
Deficient protein in Duchenne muscular dystrophy: Dystrophin
Cross-over question: Sport was related to medial epicondyle injury? A: Golf
Another cross-over question: borders of the cubital fossa:
• Superior (base): imaginary line between the medial and lateral epicondyles of the humerus
• Medial: lateral boundary of the pronator teres
• Lateral: medial border of the brachioradialis
Dr. Banzuela

• Dystrophin: stabilizes sarcolemma and prevents contraction- STEPS IN MUSCLE CONTRACTION


induced rupture (binds actin to beta-dystroglycan in the 1. Action Potential starts at the initial segment of the motor
sarcolemma) neuron, spreads through the axon, neural fibril and then the
• Actinin, CapZ Protein: binds Actin to Z lines terminal boutons.
• Desmin: binds Z lines to sarcolemma 2. At the terminal boutons, voltage-gated Ca2+ channels are
• Nebulin: acts as molecular rulers that sets the length of actin activated. Vesicles containing Ach fuses with the nerve
membrane and release Ach in the NMJ.
3. Ach binds with the Ach Receptors (NM Receptors) at the Muscle
MUSCLE CONTRACTION End Plate (MEP). This NM Receptors are ligand-gated ion
https://qrs.ly/umebg3a channels. Once they’re activated, they will open Na+ and K+
channels.
4. The open Na+ channels causes Na+ influx and produces a
Watch this video on skeletal muscle contraction first, then read the
complete steps listed below.
Miniature End Plate Potential (MEPP). MEPP summate to
Dr. Banzuela produce EPP. This depolarizes the sarcolemma.
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5. Depolarization spreads from sarcolemma to T-Tubules. At the ✔GUIDE QUESTIONS
T-Tubules, DHPR is activated. The correct temporal sequence for events at the neuromuscular junction is:
6. Once DHPR is activated, Ryanodine Receptors in the SR are also (A) action potential in the motor nerve; depolarization of the muscle
activated. end plate; uptake of Ca2+ into the presynaptic nerve terminal
7. Ryanodine Receptors then release Ca2+ from the SR to the ICF. (B) uptake of Ca2+ into the presynaptic terminal; release of
acetylcholine (ACh); depolarization of the muscle end plate
Ca2+ binds with Troponin C. (C) release of ACh; action potential in the motor nerve; action potential
8. Binding of Trop C with Ca2+ displaces Tropomyosin. This in the muscle
tropomyosin displacement causes exposure of binding sites in (D) uptake of Ca2+ into the motor end plate; action potential in the
actin for myosin. motor end plate; action potential in the muscle
9. Myosin heads binds to First Binding Site in Actin. (E) release of ACh; action potential in the muscle end plate; action
10. ATP binds to myosin head. This causes myosin to unbind with potential in the muscle 1-4 Costanzo LS. BRS Physiology. 7 ed. 2019
th

the First Binding Site in actin. At the muscle end plate, acetylcholine (ACh) causes the opening of:
11. ATP bound to myosin head undergoes partial hydrolysis, (A) Na+ channels and depolarization toward the Na+ equilibrium
potential
producing ADP. This causes “recocking” of the myosin heads.
(B) K+ channels and depolarization toward the K+ equilibrium
Myosin moves such that it now points to the Second Binding Site potential
in Actin and it moves closer to the (+) pole. (C) Ca2+ channels and depolarization toward the Ca2+ equilibrium
12. Myosin binds to Second Binding Site in actin. potential
13. ADP bound to myosin undergoes complete hydrolysis. This (D) Na+ and K+ channels and depolarization to a value halfway
causes the “power / force-generating stroke” to occur. Myosin between the Na+ and K+ equilibrium potentials
heads pull actin towards the M line or the (-) pole. A cross- (E) Na+ and K+ channels and hyperpolarization to a value halfway
bridge cycle happens. This shortens the sarcomere by 10Nm. between the Na+ and K+ equilibrium potentials
1-21 Costanzo LS. BRS Physiology. 7th ed. 2019
14. Do this again and again to have significant muscle contraction. Which of the following temporal sequences is correct for excitation–
Summate to form End Plate Potential (EPP): Miniature End-Plate contraction coupling in skeletal muscle?
Potential. EPP is an efficient action potential that involves depolarization (A)Increased intracellular [Ca2+]; action potential in the muscle
of the specialized muscle end plate membrane; cross-bridge formation
(B) Action potential in the muscle membrane; depolarization of the
Initiates action potential in the skeletal muscle fiber - sodium or calcium? T tubules; release of Ca2+ from the sarcoplasmic reticulum (SR)
Answer: Sodium. (C)Action potential in the muscle membrane; splitting of adenosine
Voltage-gated Ca Channels (not voltage gated Na Channels): induces triphosphate (ATP); binding of Ca2+ to troponin C
release of neurotransmitters in the neuromuscular junction. It is (D)Release of Ca2+ from the sarcoplasmic reticulum (SR);
associated with muscle conduction before muscle contraction depolarization of the T tubules; Action potential in the muscle
Dr. Banzuela membrane 1-24 Costanzo LS. BRS Physiology. 7 ed. 2019 th

STEPS IN MUSCLE RELAXATION In skeletal muscle, which of the following events occurs before
1. Remove the Ca2+ from Troponin C. depolarization of the T Tubules in the mechanism of excitation–
2. Tropomyosin the goes back to its original location, covering the contraction coupling?
binding site of actin for myosin. (A) Depolarization of the sarcolemmal membrane.
3. Place the Ca2+ back to the SR using SERCA. (B) Opening of Ca2+ release channels on the sarcoplasmic reticulum
4. Use Acetylcholinesterase to degrade ACh to Acetate and Choline. (SR)
(C) Uptake of Ca2+ into the SR by Ca2+-adenosine triphosphatase
5. Choline may undergo reuptake.
(ATPase)
(D) Binding of Ca2+ to troponin C
(E) Binding of actin and myosin 1-26 Costanzo LS. BRS Physiology. 7 ed. 2019 th

The steps in muscle contraction and relaxation are not just important
medically, they are also board-relevant. Review them again, and if you have
problems understanding or memorizing them, message me on FB
messenger.
Dr. Banzuela
DRUGS THAT AFFECT THE NMJ
DESCRIPTION ANSWER
Blocks release of Ach from
BOTULINUM TOXIN
pre-synaptic terminals
Competes with Ach for
CURARE
receptors on Motor End Plate
Inhibits Acetylcholinesterase NEOSTIGMINE
Blocks reuptake of Choline
HEMICHOLINIUM
into presynaptic Terminal
Super favorite yang table na yan above. Suki na. Memorize.
Dr. Banzuela

• Mechanism behind botulinum type A (Botox) smoothing out


glabellar lines: Blocks the release of synaptic transmitter from
© Topnotch Medical Board Prep
alpha motoneurons (specifically acetylcholine)

✔GUIDE QUESTION
A 42-year-old man with myasthenia gravis notes increased muscle
strength when he is treated with an acetylcholinesterase (AChE)
inhibitor. The basis for his improvement is increased
(A) amount of acetylcholine (ACh) released from motor nerves
(B) levels of ACh at the muscle end plates
(C) number of ACh receptors on the muscle end plates
(D) amount of norepinephrine released from motor nerves
(E) synthesis of norepinephrine in motor nerves
1-8 Costanzo LS. BRS Physiology. 7th ed. 2019
Neostigmine is part of the treatment for MG. By inhibiting AChase, ACh
levels will increase, decreasing muscle weakness.
Dr. Banzuela

ISOTONIC VS ISOMETRIC CONTRACTION


• Isometric Contraction
o Length is held constant while muscle contracts
© Topnotch Medical Board Prep
§ Force generated is not enough to move or lift an object
o No muscle shortening/lengthening
o e.g., pushing against the wall

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• Isotonic Contraction • Phase 3: Repolarization
o Load is held constant while muscle contracts Decrease Ca2+ influx and increased K+ efflux
o With muscle shortening: concentric contraction • Phase 4: Resting membrane potential
(e.g., pulling a weight up)
o With muscle lengthening: eccentric contraction
(e.g., lowering a weight down)
Iso means “same.” iso-METRIC (length) means “same length”. Iso-TONIC
(tone of muscle) means “same tone”. Isometric contraction is muscle
contraction with same muscle length – no shortening/lengthening.
Isotonic contraction means same muscle tone – there is change in muscle
length, but due to a constant load on the muscle, same muscle tone.
Isometric contraction – think of pushing against an immovable wall –
there’s muscle contraction but no change in muscle length. Isotonic
contraction – think of holding objects in midair – there’s a constant load on
the muscle causing a constant tone.
Dr. Banzuela
SPECIAL NOTES ON MUSCLE CONTRACTION
© Topnotch Medical Board Prep
• In Skeletal Muscle Contraction: CALCIUM REGULATION OF CARDIAC MUSCLES
o More tension produced in isometric contractions than isotonic • Increases Intracellular Calcium
contractions o L-Type or Slow-Calcium channel: major & voltage-gated
o More work (force x distance) produced in isotonic o T-Type or Fast-Calcium channel
contractions than isometric contractions
• Decreases Intracellular Calcium
o Muscle Fiber has no refractory period: repeated stimulation
o 3Na+-1Ca2+ Countertransport
before relaxation can result in incomplete or complete tetany
o Ca2+-ATPase pump
o Muscle contraction starts BEFORE action potential is over and
last LONGER than the action potential
• Preload: muscle length
• Afterload: load against which the muscle contracts
o Velocity of muscle shortening decreases as afterload increases
• Passive Tension: tension due to muscle stretch
• Active Tension: tension due to muscle contraction; proportional
to number of cross-bridge cycles formed
• Rigor Mortis: usually occurs 3-6 hours after death due to lack of ATP
• Tetanus / Tetanic Spasm: happens when all Ca2+ from the SR has
been released; no further increase in muscle strength
o sustained muscle contraction (tetanus) is due to accumulation
of CALCIUM
✔GUIDE QUESTIONS
Which of the following causes rigor in skeletal muscle? © Topnotch Medical Board Prep
(A) No action potentials in motoneurons REFRACTORY
(B) An increase in intracellular Ca2+ level DESCRIPTION
PERIODS
(C) A decrease in intracellular Ca2+ level
(D) An increase in adenosine triphosphate (ATP) level Absolute • Begins at the upstroke of the action potential
(E) A decrease in ATP level 1-29 Costanzo LS. BRS Physiology. 7 ed. 2019 th Refractory and ends after the plateau
“Rigor” here refers to rigor mortis. When you die → calcium enters cells Period (ARP) • No action potential can be INITIATED
→ calcium binds to trop C → binding of myosin head to actin occurs. • Longer than ARP
Since there is no more ATP produced when you die, no more unbinding Effective
• Conducted action potential cannot be
of myosin from actin. This will cause muscle rigidity – this will cause Refractory
elicited
rigor mortis. Rigor mortis happens around 3-6 hours after death. It will Period (ERP)
eventually end when proteolysis (another one of the changes in death) • No action potential can be PROPAGATED
occurs. Relative • Occurs after ARP
Dr. Banzuela Refractory • Action potential is possible but will require
Repeated stimulation of a skeletal muscle fiber causes a sustained Period (RRP) more than usual inward current
contraction (tetanus). Accumulation of which solute in intracellular fluid
is responsible for the tetanus? SA NODE ACTION POTENTIAL
(A) Na+ (D) Mg2+ • SA Node and AV node have prominent pacemaker or
(B) K+ (E) Ca2+ prepotentials
1-6 Costanzo LS. BRS Physiology. 7 ed. 2019
(C) Cl– th

o SA Node has a slowly depolarizing prepotential due to slow Na


influx
1.7 CARDIAC MUSCLES • Phase 4: slow Na+ Influx towards threshold
CARDIAC MUSCLE • Phase 0: Ca++ Influx (depolarization)
• Skeletal Muscle: relies purely on intracellular Ca2+ (SR Ca2+) • Phase 3: K+ Efflux (repolarization)
• Smooth Muscle: relies mainly on extracellular Ca2+ (ECF Ca2+)
• Cardiac Muscle: relies on both intracellular and extracellular Ca2+
• “Calcium-Induced Calcium-Release” system
o seen in smooth and cardiac muscles

CARDIAC
ACTION POTENTIAL
https://qrs.ly/ywdpcuo

Watch this video and refer to the graphs on Cardiac and SA Node Action
Potential on the next page, © Topnotch Medical Board Prep
Dr. Banzuela
✔ GUIDE QUESTIONS
CARDIAC ACTION POTENTIAL
Which of the following is the result of an inward Na+ current?
• Phase 0: Due to Na+ influx (A) Upstroke of the action potential in the sinoatrial (SA) node
• Phase 1: Brief period of repolarization (B) Upstroke of the action potential in Purkinje fibers
Due to K+ efflux and decrease in Na+ influx (C) Plateau of the action potential in ventricular muscle
• Phase 2: Plateau of AP (D) Repolarization of the action potential in ventricular muscle
Due to Ca2+ influx (E) Repolarization of the action potential in the SA node
3-29. Costanzo LS. BRS Physiology. 7th ed. 2019.

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✔ GUIDE QUESTIONS SINGLE-UNIT /
In the sinoatrial (SA) node, phase 4 depolarization (pacemaker UNITARY SMOOTH MUSCLE /
MULTI-UNIT SMOOTH MUSCLE
potential) is attributable to SYNCYTIAL SMOOTH MUSCLE /
(A) an increase in K+ conductance VISCERAL SMOOTH MUSCLE
(B) an increase in Na+ conductance No true AP (no propagation!); Slow waves, spike potentials and
(C) a decrease in Cl− conductance Junctional potential only plateau potentials
(D) a decrease in Ca2+ conductance May exhibit spontaneous
(-) Spontaneous contractions
(E) simultaneous increases in K+ and Cl− conductance contractions
3-34. Costanzo LS. BRS Physiology. 7th ed. 2019.
E.g., Ciliary eye muscle, iris, E.g., Intestines, bile ducts, ureters,
Remember: the slope of phase 4 in the SA Node Action Potential is the one piloerector muscle, vas deferens uterus
that determines heart rate. Sympathetic and Parasympathetic NS may
affect this slope. Multi-Unit Smooth muscle is for FINE MOTOR CONTROL. Unitary Smooth
Dr. Banzuela
muscle is for GROSS/COARSE MOTOR CONTROL. Ang uterus, unitary
smooth muscles yan → gross motor control ang kailangan kasi. Ang
1.8 SMOOTH MUSCLES smooth muscles naman controlling pupillary size, multi-unit smooth
SMOOTH MUSCLE muscles yan → fine motor control ang kailangan kasi.
Dr. Banzuela
• No Troponin
• Contains
o Myosin-Light Chain Kinase (MLCK): phosphorylates and
activates myosin heads
o Myosin-Light Chain Phosphatase (MLCP): dephosphorylates
and inactivates myosin heads
o Calmodulin: binds with Ca
o Caldesmon and Calponin: inhibits muscle contraction
o Dense Bodies: analogous to Z lines
o Rudimentary SR
o Rudimentary T-Tubules (Caveoli)
• Main difference in contraction of smooth muscles vs. skeletal
muscles: role of Ca2+ in initiating contraction
To emphasize: MLCK causes smooth muscle CONTRACTION. MLCP
causes smooth muscle RELAXATION. Calmodulin is analogous to
Troponin C – it binds with calcium. Caldesmon is analogous to Troponin I © Topnotch Medical Board Prep
– it inhibits actin-myosin interaction.
Dr. Banzuela
TYPES OF SMOOTH MUSCLES STEPS IN SMOOTH MUSCLE CONTRACTION & RELAXATION
SINGLE-UNIT / 1. Hormones, NTs, stretch triggers increased ICF Ca2+
MULTI-UNIT SMOOTH MUSCLE
UNITARY SMOOTH MUSCLE / 2. ICF Ca2+ binds with Calmodulin
SYNCYTIAL SMOOTH MUSCLE / 3. Calcium-Calmodulin Complex activates MLCK
VISCERAL SMOOTH MUSCLE
4. MLCK phosphorylates (and activates) Myosin Heads
One nerve, multiple muscle One nerve, multiple muscle fibers 5. Activated Myosin Heads: causes smooth muscle contraction
fibers that may act on their own that are act together as one 6. MLCP dephosphorylates (and inactivates) Myosin Heads
7. Inactivated Myosin Heads: causes smooth muscle relaxation
Mainly controlled by nerve signals
Controlled mainly by nerve • Responsible for relaxation of contracted smooth muscles and
(ACh, NE) & non-nerve signals
signals (ACh, NE)
(hormones, stretch, local factors) formation of latch bridges: Dephosphorylation of actomyosin
(-) Gap junctions (+) Gap junctions

© Topnotch Medical Board Prep

1.9 COMPARISON OF SKELETAL MUSCLES, SMOOTH MUSCLES AND CARDIAC MUSCLES


SKELETAL CARDIAC SMOOTH MUSCLE
Sarcomeres,
(+) (+) (-)
striations, troponin
Mitochondria 3-8% of skeletal muscle volume 35% of cardiac muscle volume 3-5% of smooth muscle cell volume
• Ca2+ Influx (SA Node);
Upstroke of AP Na+ Influx • Na+ Influx (atria, ventricles, Purkinje Ca2+ Influx
Fibers)
• No (SA Node)
Plateau No No
• Yes (atria, ventricles, Purkinje Fibers)
• 150 msec (SA Node, Atria)
AP Duration 1 msec 10 msec
• 250-300 sec (ventricles, Purkinje Fibers)
• AP opens cell membrane voltage-
Excitation-
gated Ca2+ channels;
Contraction Use of SR Calcium Ca2+-induced Ca2+-Release
• Hormones & NTs open IP3-gated SR
Coupling
Ca2+ Channels
Gap Junctions (-) (+) (+) only for unitary smooth muscles
SR Greatest --- Least
Regulation Actin-Based using Tropomyosin Actin-Based using Tropomyosin Myosin-Based using MLCK
Among the types of muscles, cardiac muscles have the greatest number of mitochondria due to the heart’s energy requirements. Take note that 90% of the
heart’s ATP requirements is met by cardiac mitochondria through beta-oxidation of fats at rest.
Poorly-developed or lacking in atrial myocytes: T-Tubules
Dr. Banzuela

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✔GUIDE QUESTIONS ANS RECEPTORS: ADRENORECEPTORS (SYMPA)


Which characteristic or component is shared by skeletal muscle and ADRENO-
smooth muscle? MOA EFFECT
RECEPTOR
(A) Thick and thin filaments arranged in sarcomeres Gq
(B) Troponin Alpha-1
protein • Causes smooth muscle
(C) Elevation of intracellular [Ca2+] for excitation–contraction Receptors
coupling ↑ contraction
(𝛂1)
(D) Spontaneous depolarization of the membrane potential IP3/Ca2+
(E) High degree of electrical coupling between cells • Seen in sympathetic
1-5. Costanzo LS. BRS Physiology. 7th ed. 2019.
postganglionic presynaptic nerve
Remember this personal mnemonic of mine: Calcium is to muscle what
spinach is to Popeye. It provides you with power, the stimulus for
terminals. Also seen in platelet,
Alpha-2 Gi
contraction. fat cells, walls of the GIT
Receptors protein
Dr. Banzuela • Inhibits release of NE for
In contraction of gastrointestinal smooth muscle, which of the following (𝛂 2) ↓ cAMP
presynaptic nerve terminals →
events occurs after binding of Ca2+ to calmodulin? inhibits sympathetic effects,
(A) Depolarization of the sarcolemmal membrane
promotes parasympathetic effects
(B) Ca2+-induced Ca2+ release
(C) Increased myosin-light chain kinase Beta-1 Gs • Seen in the heart (SA Node, AV
(D) Increased intracellular Ca2+ concentration Receptors protein Node, ventricles) and kidneys
(E) Opening of ligand-gated Ca2+ channels (𝛃1) ↑ cAMP • Causes excitation
1-34. Costanzo LS. BRS Physiology. 7th ed. 2019.
Beta-2 Gs
• Causes smooth muscle
Receptors protein
2. NEUROPHYSIOLOGY relaxation
(𝛃 2) ↑ cAMP
1. Autonomic Nervous System (ANS) Beta-3 Gs
2. Sensory Systems Receptors protein • Causes lipolysis (major effector)
3. Motor Systems (𝛃 3) ↑ cAMP
4. Higher Functions of the Cerebral Cortex
5. Blood-Brain Barrier and Cerebrospinal Fluid (CSF) For the discussion on G proteins, and 2nd messengers like cAMP, go to the
6. Temperature Regulation Endocrine Physiology Module.
Dr. Banzuela
ANS RECEPTORS: CHOLINOCEPTORS (BOTH SYMPA & PARA)
2.1 AUTONOMIC NERVOUS SYSTEM (ANS) RECEPTOR LOCATION MOA
NICOTINIC RECEPTORS
• binds with ACh,
ANS NM (N1) Skeletal Muscle MEP
• opens Na-K Channel
https://qrs.ly/izebg5c
Autonomic Ganglia • binds with Ach
NN (N2) (dendrites of
Postganglionic Neurons) • opens Na-K Channel
Watch this video on ANS first, then read and highlight the portions below. MUSCARINIC RECEPTORS
Dr. Banzuela
NERVOUS SYSTEM • binds with Ach, Gq,
M1 CNS
• Somatic Nervous System: voluntary, 1-motor neuron system • ↑ IP3/Ca2+
• Autonomic Nervous System (ANS): involuntary, 2-motor neuron • binds with Ach, Gi,
M2 Heart
system • ↓ cAMP
o Sympathetic Nervous System:” Fight or Flight”; capable of Glands • binds with Ach,
M3
mass discharge smooth muscles • Gq, ↑ IP3/Ca2+
o Parasympathetic Nervous System:” Rest and Digest” for the other subjects, be careful of the terms: “nicotinic, cholinergic” or
• Enteric Nervous System: involuntary, subject to ANS control BUT “muscarinic cholinergic” or “adrenergic”.
can function independently of the ANS Autonomic receptors that act by IP3: Alpha-1, M1, M3
o Also called the “second brain” since it utilizes neurons and
neurotransmitters similar to the central nervous system
o NOT part of the autonomic nervous system
o Submucosal Plexus: for secretions
o Myenteric Plexus: for motility
o Neurotransmitter of the enteric nervous system: Acetylcholine
(major), dopamine, serotonin

AUTONOMIC NERVOUS SYSTEM (ANS)


• Two-Motor Neuron System:
o Preganglionic Neuron synapses with Postganglionic neuron.
o Postganglionic neuron synapses with effector organ receptors
• Preganglionic Neuron
o Sympathetic Nervous System (Sympa): Cell Body is in the
Thoracic and Lumbar segment of the Spinal Cord
(thoracolumbar distribution)
o Parasympathetic Nervous System (Para): Cell Body is in the
Brainstem, Sacral Segment of the Spinal Cord (craniosacral © Topnotch Medical Board Prep.

distribution) ✔GUIDE QUESTIONS


• Postganglionic Neuron Which autonomic receptor is blocked by hexamethonium at the ganglia,
but not at the neuromuscular junction?
o Sympa: Cell Body is in the Paravertebral or Prevertebral
(A) Adrenergic α1 receptors
Ganglia (B) Adrenergic β1 receptors
o Para: Cell Body is in the Ganglia at the walls of Effector Organs (C) Adrenergic β2 receptors
(D) Cholinergic muscarinic receptors
ANS NEUROTRANSMITTERS (E) Cholinergic nicotinic receptors 2-1. Costanzo LS. BRS Physiology. 7 ed. 2019.
th

• Adrenergic Neurons: release NE (sympa) Hexamethonium is a non-depolarizing ganglionic blocker


• Cholinergic Neurons: release Ach (sympa or para) Dr. Banzuela
Which autonomic receptor mediates secretion of epinephrine by the
• Nonadrenergic, noncholinergic Neurons: release Substance P, adrenal medulla?
Vasointestinal Peptide (VIP) and Nitric Oxide (NO) (some (A) Adrenergic α1 receptors
postganglionic parasympathetic neurons of the GIT) (B) Adrenergic β1 receptors
(C) Adrenergic β2 receptors
(D) Cholinergic muscarinic receptors
(E) Cholinergic nicotinic receptors 2-16. Costanzo LS. BRS Physiology. 7 ed. 2019. th

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✔GUIDE QUESTIONS ✔GUIDE QUESTIONS
Which autonomic receptor is activated by low concentrations of • Best initial treatment for pheochromocytoma: alpha-adrenergic
epinephrine released from the adrenal medulla and causes vasodilation? antagonist like Phentolamine, Propranolol (beta-blocker) is also
(A) Adrenergic α1 receptors given.
(B) Adrenergic β1 receptors • Hallmark of pheochromocytoma: HPN
(C) Adrenergic β2 receptors
(D) Cholinergic muscarinic receptors MNEMONICS AUTONOMIC NERVOUS SYSTEM
(E) Cholinergic nicotinic receptors 2-27. Costanzo LS. BRS Physiology. 7 ed. 2019. th PLASMA OPPOSITE
Remember: Beta-2 will always cause smooth muscle RELAXATION P arasympathetic S ympa
while Alpha-1 will always cause smooth muscle CONTRACTION. L ong Pre-Ganglionic Tract S hort Pre-Ganglionic Tract
Dr. Banzuela
A ch used A ch used pa rin
A 42-year-old woman with elevated blood pressure, visual disturbances,
and vomiting has increased urinary excretion of 3-methoxy-4- S hort Post-Ganglionic Tract L ong Post-Ganglionic Tract
hydroxymandelic acid (VMA). A computerized tomographic scan shows M uscaric Receptors A drenergic Receptors
an adrenal mass that is consistent with a diagnosis of A ch used E pi, NE used
pheochromocytoma. While awaiting surgery to remove the tumor, she is
treated with phenoxybenzamine to lower her blood pressure. What is the MNEMONICS AUTONOMIC NERVOUS SYSTEM
mechanism of this action of the drug? “QISS AND QIQ (KISS AND KICK)”
(A) Increasing cyclic adenosine monophosphate (cAMP) G-proteins from 𝛼1- β2 and M1-M3
(B) Decreasing cAMP
(C) Increasing inositol 1,4,5-triphosphate (IP3)/Ca2+ How to Memorize Muscarinic Receptor Locations
(D) Decreasing IP3/Ca2+ Parang pagmamahal lang yan. Remember M = Mahal.
(E) Opening Na+/K+ channels Ano ba ang dapat sundin pag nagmamahal?
(F) Closing Na+/K+ channels 2-35. Costanzo LS. BRS Physiology. 7 ed. 2019 th 1st: you listen to your Brain (M1=CNS)
Phenoxybenzamine is an alpha-1 antagonist. Alpha-1 MOA involves 2nd: you listen to your Heart (M2= Heart)
increased IP3/Ca2+. Phenoxybenzamine will decrease that. Take note 3rd: you listen to your, ahem, “Other Organs"
that Phenoxybenzamine will actually block both alpha-1 and alpha-2 (M3 = other organs)
but it has some selectivity (more potent) for alpha-1.
Dr. Banzuela

SYMPATHETIC PARASYMPATHETIC
ORGAN SYMPATHETIC ACTION PARASYMPATHETIC ACTION
RECEPTOR RECEPTOR
↑ heart rate β1 ↓ heart rate M2
Heart ↑ contractility β1 ↓ contractility (atria) M2
↑ AV node conduction β1 ↓ AV node conduction M2
Constricts blood vessels in α1 ⏤
skin; splanchnic
Vascular smooth
muscle
Dilates blood vessels in β2 ⏤
skeletal muscle
↓ motility α2’ β2 ↑ motility M3
Gastrointestinal tract
Constrict sphincters α1 Relaxes sphincters M3
Dilates bronchiolar smooth β2 Constricts bronchiolar smooth M3
Bronchioles
muscle muscle
Male sex organs Ejaculation α1 Erection M
Relaxes bladder wall β2 Contracts bladder wall M3
Bladder
Constricts sphincter α1 Relaxes sphincter M3
M (sympathetic
Sweat glands ↑ sweating ⏤
cholinergic)
Eye
Radial muscle, iris Dilates pupil (mydriasis) α1 ⏤
Circular sphincter
⏤ Constricts pupil (miosis) M
muscle, iris
Ciliary muscle Dilates (far vision) β Contracts (near vision) M
Kidney ↑ renin secretion β1 ⏤
Fat cells ↑ lipolysis β1 ⏤
Table 2.4. Costanzo LS. BRS Physiology. 7th ed. 2019.
Please be careful in differentiating miosis from ptosis since they sound alike. Miosis is decreased pupillary aperture. Ptosis is drooping of the eyelid.
Autonomic receptor involved in ejaculation: Alpha-1 receptor
Dr. Banzuela

✔GUIDE QUESTIONS ✔GUIDE QUESTIONS


Which of the following is a feature of the sympathetic, but not the A 66-year-old man with chronic hypertension is treated with prazosin by
parasympathetic, nervous system? his physician. The treatment successfully decreases his blood pressure to
(A) Ganglia located in the effector organs within the normal range. What is the mechanism of the drug’s action?
(B) Long preganglionic neurons (A) Inhibition of β1 receptors in the sinoatrial (SA) node
(C) Preganglionic neurons release norepinephrine (B) Inhibition of β2 receptors in the SA node
(D) Preganglionic neurons release acetylcholine (ACh) (C) Stimulation of muscarinic receptors in the SA node
(E) Preganglionic neurons originate in the thoracolumbar spinal (D) Stimulation of nicotinic receptors in the SA node
cord 2-7. Costanzo LS. BRS Physiology. 7 ed. 2019.
th (E) Inhibition of α1 receptors on vascular smooth muscle
2-2. Costanzo LS. BRS Physiology. 7th ed. 2019.
Sympa will use thoracic nerves and lumbar nerves (thoracolumbar).
Para will use cranial nerves and sacral nerves (craniosacral). Alpha-1 in the blood vessels causes vasoconstriction. Inhibiting alpha-
Remember this mnemonic for the cranial nerves utilized by the 1 can therefore lower BP.
Dr. Banzuela
parasympathetic nervous system: 1973 (CN X, IX, VII, III). Hindi 1972 Which of the following responses is mediated by parasympathetic
(Vit-K dependent clotting factors yun). Hindi rin 1975 (mixed motor- muscarinic receptors?
sensory CN yun) Wag malillito sa 1972, 1973, 1975 J (A) Dilation of bronchiolar smooth muscle
Dr. Banzuela
Which autonomic receptor mediates an increase in heart rate? (B) Erection
(A) Adrenergic α1 receptors (C) Ejaculation
(B) Adrenergic β1 receptors (D) Constriction of gastrointestinal (GI) sphincters
(C) Adrenergic β2 receptors (E) Increased cardiac contractility 2-3. Costanzo LS. BRS Physiology. 6 ed. 2014.
th

(D) Cholinergic muscarinic receptors There’s an old mnemonic for this: “Point and Shoot.” Point (Para) is
(E) Cholinergic nicotinic receptors 2-8. Costanzo LS. BRS Physiology. 7 th ed. 2019.
erection. Shoot (Sympa) is ejaculation.
Dr. Banzuela
Remember: puso at bato, Beta-1.
Dr. Banzuela

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✔GUIDE QUESTIONS AUTONOMIC CENTERS AND CEREBRAL CORTEX
Administration of which of the following drugs is contraindicated in a CHARACTERISTICS AREA
10-year-old child with a history of asthma? • Vasomotor Center, Respiratory
(A) Albuterol (D) Norepinephrine MEDULLA
Center (DRG, VRG), Swallowing,
(B) Epinephrine (E) Propranolol
(C) Isoproterenol 2-12. Costanzo LS. BRS Physiology. 6 ed. 2014 th
Coughing & Vomiting Centers
Because propranolol is non-selective beta-blocker. It will also block • Micturition Center, Pneumotaxic,
PONS
beta-2 receptors – the ones responsible for bronchodilation. You don’t Apneustic Centers
want that in a patient with asthma. • Temperature Regulation
BTW, Isoproterenol is a non-selective beta-agonist that increases HYPOTHALAMUS
• Thirst, Food Intake
pulmonary blood flow and decreases pulmonary vascular
resistance • Relay Center for almost all
THALAMUS
Dr. Banzuela sensations, Memory Recall
Patients are enrolled in trials of a new atropine analog. Which of the • Motor, Personality, Calculation,
following would be expected? FRONTAL LOBE
Judgment
(A) Increased AV node conduction velocity
(B) Increased gastric acidity (D) Sustained erection • Somatosensory Cortex PARIETAL LOBE
(C) Pupillary constriction (E) Increased sweating • Vision OCCIPITAL LOBE
2-12. Costanzo LS. BRS Physiology. 6th ed. 2014
Atropine is anti-muscarinic. It will therefore promote mainly
• Hearing, vestibular processing,
sympathetic effects – in this case, choice A. Choice E is not the correct recognition of faces, TEMPORAL LOBE
answer since sweating, even if it is sympathetic, utilizes muscarinic • optic pathway (Meyer Loop)
receptors as final receptors. • Behavior, Emotions, Motivation LIMBIC LOBE
Dr. Banzuela
Just for fun. Student asked me this question - which part of the brain is then
PROTOTYPES OF DRUGS THAT AFFECT AUTONOMIC ACTIVITY most needed in catching a fly? Answer: the cerebral cortex – since
Type of judgment and integration of various parts of the brain occurs here. Take
Agonist Antagonist
Receptor note that the Cerebellum, Basal ganglia are also needed.
Adrenergic Component of the limbic system that start and ends with the hippocampus
Norepinephrine Phenoxybenzamine and involved in emotional expression: Papez Circuit
a1
Phenylephrine Phentolamine, Prazosin Dr. Banzuela

a2 Clonidine Yohimbine 2.2 SENSORY SYSTEMS


Norepinephrine SENSATION
Propranolol
b1 Isoproterenol • Sends info to the Brain about the state of the body and/or the
Metoprolol
Dobutamine immediate environment
Isoproterenol Propranolol • Sensory Systems encode for Modality, Location, Intensity,
b2
Albuterol Butaxamine Duration
Cholinergic • Divided into:
Curare o Somatic Sensation (Somatosensory)
ACh (neuromuscular junction N1
o Special Senses
Nicotinic Nicotine receptors)
Hexamethonium SENSORY RECEPTORS
Carbachol
(ganglionic N2 receptors) • Specialized epithelial cells or neurons that converts
ACh environmental signals into neural signals
Muscarinic Muscarine Atropine • Can detect chemical, mechanical, light, sound, etc.
Carbachol • Types:
o Mechanoreceptors: Pacinian corpuscles, joint receptors, muscle
SPECIAL NOTES ON THE ANS stretch receptors, auditory hair cells, baroreceptors
• Singly-Innervated Areas o Thermoreceptors: Temperature Receptors
SYMPATHETIC ONLY PARASYMPATHETIC ONLY § unmyelinated/lightly myelinated, innervated by Type A Delta
• Sweat glands • Lacrimal muscle (tear Fibers and Type C Fibers, found in both hairy and glabrous
• Adrenal glands glands) skin and deep tissues, warmth threshold: 30°C, cold
• Most blood vessels • Ciliary muscle (for threshold: 24°C, cold receptors inactive again at <10°C
• Pilomotor muscle accommodation) o Nociceptors: Pain
• Cardiac Ventricles § activated by strong pressure, severe cold/heat, chemicals,
• Pregnant Uterus organ distention in the viscera
§ Unmyelinated, innervated by Type A Delta Fibers and Type
• Adrenal Medulla: C Fibers
o Not essential for life; supplements sympathetic effects o Electromagnetic Receptors: rods and cones (location: RETINA)
especially during exercise o Chemoreceptors: olfactory receptors, taste receptors, receptors
o Chromaffin cells in the adrenal medulla are migrated neural to detect O2 and CO2
cells that secretes Epi (80%) and NE (20%) • MOA: Ion channels open, causing current to flow, producing
• Sympathetic distribution, but final NT is Ach and final receptor depolarization (or rarely, in the case of photoreceptors,
is Muscarinic: hyperpolarization)
o Sweat glands (some, not all) • Depolarization causes receptor potential / generator potential
o Piloerector muscles (controversial, utilizes 𝛼1 according to o Change in membrane potential produced by stimulus
some sources)
o Not a True AP: Merely brings you closer to threshold
o 𝜷3 Receptors: seen in Brown Adipose Tissue of babies
o increases in amplitude as more intense stimulus is applied
Refer to the audio guide as you read the table below:

AUTONOMIC CENTERS
AND CEREBRAL CORTEX
https://qrs.ly/iqebg89
Dr. Banzuela

Function of the Edinger-Westphal nucleus: pupil contriction and lens


accommodation

Innervation of the lacrimal gland: Lacrimal nerve (branch of opthalmic © Topnotch Medical Board Prep
nerve which is a branch of CN V) To emphasize: A Receptor Potential/Generator potential is NOT a true
Dr. Banzuela action potential – it merely brings you closer to threshold. “Slow waves”
(to be discussed in the GI module), are also not true action potentials.
Dr. Banzuela

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✔GUIDE QUESTION • Has a Receptive Field: skin region controlled by each sensory
Sensory receptor potentials neuron
(A) are action potentials o Maybe excitatory or inhibitory receptive field
(B) always bring the membrane potential of a receptor cell toward o Types:
threshold § Type 1 Receptive Field: smaller with well-defined borders
(C) always bring the membrane potential of a receptor cell away from § Type 2 Receptive Field: wider but with poorly-defined
threshold borders
(D) are graded in size, depending on stimulus intensity
(E) are all-or-none 2-29. Costanzo LS. BRS Physiology. 7 ed. 2019 th

• Exhibits adaptation: change in a way a receptor responds to


sequential or prolonged stimulation
o “adapt” = “manhid” = non-responsive to stimuli
• Slowly-adapting Receptors (Tonic Receptors)
o for continuous stimulus strength (detects steady stimulus)
o e.g., Muscle Spindle, Golgi Tendon, Slow Pain Receptor,
Baroreceptor, Chemoreceptor, Pressure
• Rapidly-adapting Receptors (Phasic Receptors)
o for detecting change in stimulus strength (detects onset and
offset of stimulus)
o Has a Predictive function
o e.g., Pacinian Corpuscle, Light Touch
When sensory receptors “adapt”, they become non-responsive. So you © Topnotch Medical Board Prep
have two types of receptors – “martyrs” and “players”. Slowly-adapting
receptors are “martyrs” – as long as you love them, kahit kaunti lang, they Importante yang Receptive Field Types. Don’t ignore these. A receptive
will love you back. As long as may stimulus, may response pa rin yung field is a region controlled by a single sensory neuron. Pag type 1, small
sensory receptor. Matagal sila mag “adapt”; matagal sila maging manhid. area but with well-defined borders. Pag type 2, large areas, pero poorly
Rapidly-adapting receptors are “players” – ang dali nila magsawa, ang defined ang borders. Which is therefore best for 2-point discrimination
dali nila maging “manhid.” Kahit mahal mo pa sila, hindi ka na nila mahal. (ability to detect two separate touch stimuli as two discrete points)? Type
Kahit may stimulus pa, wala nang response yung sensory receptors. They 1 is the answer – kasi smaller areas with well-defined borders ang
only enjoy the start and end of relationships – they only detect the onset kontrolado ng bawat sensory neuron na may Type 1 receptive field.
Dr. Banzuela
and offset of stimulus. See the pictures below:
Dr. Banzuela
SENSORY NERVE FIBER
• Bundles of axons joined together that vary in thickness,
myelination, conduction velocity, fidelity
Listen to this audio guide as you look at the table below about nerve fibers:

NERVE FIBERS
https://qrs.ly/lndpl5h

IMPORTANT POINTS SENSORY NERVE FIBERS


TYPE A (Type I): Thicker, More Myelinated, Faster
For temporal and spatial fidelity
TYPE C (Type IV): Thinner, Unmyelinated, Slower
Less Energy-requiring
Most Least
Agent Intermediate
Susceptible Susceptible
Hypoxia B A C
Pressure A B C
© Topnotch Medical Board Prep Local
C B A
Anesthetics
Adapted from Table 4-3. Barrett et al. Ganong’s Review of Medical Physiology. 26th ed. 2019

General Fiber Type and Example Sensory Fiber Type and Example Diameter Conduction Velocity
Ia
Largest Fastest
A-alpha (“skeletomotor fibers”) Muscle spindle afferents
Large α-motoneurons Ib
Largest Fastest
Golgi tendon organs
A-beta II
Medium Medium
Touch, pressure Secondary afferents of muscle spindles; touch and pressure
A-gamma
y- Motoneurons to muscle spindles ⏤ Medium Medium
(intrafusal fibers)
A-delta III
Small Medium
Touch, pressure, temperature, and pain Touch, pressure, fast pain, and temperature
B
⏤ Small Medium
Preganglionic autonomic fibers
C IV
Smallest Slowest
Slow pain; postganglionic autonomic fibers Pain and temperature (unmyelinated)
Table 2.5. Costanzo LS. BRS Physiology. 7th ed. 2019.
Contains nerve fiber with fastest conduction velocity: Skeletomotor Fibers (nerve fibers of Alpha motorneurons)
Sensory fiber used in touch, pressure, fast pain, and temperature: Group III (Type A Delta)
Dr. Banzuela

✔GUIDE QUESTION SENSORY PATHWAY:


Which of the following is a property of C fibers? SENSORY RECEPTOR TO THE SENSORY CORTEX
(A) Have the slowest conduction velocity of any nerve fiber type
(B) Have the largest diameter of any nerve fiber type • Sensory Receptors
(C) Are afferent nerves from muscle spindles o Transduces stimulus to electrical signal
(D) Are afferent nerves from Golgi tendon organs • First-order Neurons
(E) Are preganglionic autonomic fibers o Cell Body: Dorsal Root or Cranial Nerve Ganglia
2-4. Costanzo LS. BRS Physiology. 7th ed. 2019

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• Second-order Neurons SOMATOSENSORY CORTEX
o Cell Body: Spinal Cord or Brainstem • Primary Somatosensory Area (S1) and Secondary Somatosensory
o Axons may decussate Area (S2) has somatotopic organization (Sensory Homunculus)
• Third-order Neurons • Largest representation in the sensory homunculus: hands, face,
o Cell Body: Relay Nucleus of the Thalamus tongue
• Fourth-order Neurons o This is for precise localization in those areas
o Cell Body: Sensory Cortex TYPES OF PAIN
o Results in conscious perception of stimulus FAST / FIRST PAIN SLOW / SECOND PAIN
SOMATOSENSORY PATHWAYS: • after 0.1 sec of stimulus • After 1 sec of stimulus
TOUCH, MOVEMENT, TEMPERATURE, PAIN • Associated with tissue
destruction
DORSAL COLUMN-MEDIAL ANTERO-LATERAL SYSTEM
LEMNISCUS PATHWAY (SPINOTHALAMIC TRACT) • Superficial; • Poorly-localized
Uses large myelinated fibers • rapid onset and offset; • if VISCERAL PAIN: poorly-
Uses smaller myelinated fibers • localized localized, (+) nearby skeletal
(Type II), conduction velocity
(Type III, IV), 8-40 m/s muscle spasm, slow
30-110 m/s
With temporal and spatial adaptation, uses Type C Fibers
Less fidelity
fidelity • Stimulated by mechanical, • Stimulated by mechanical,
Decussates near the medulla Decussates immediately thermal stimuli thermal, chemical stimuli
• Touch sensations requiring • Pain • Type A-delta fibers or Type III • Type C fibers or Type IV
high degree of localization & • Temperature Sensation (nerve velocity 6-30 m/sec) (0.5-2m/sec)
fine gradation of intensity • Light Touch and Pressure • NT: Substance P (relieved
• Vibration Sensation by opioids)
• NT: Glutamate
• Sensations that signal • Tickle and Itch Sensation • Mediates synaptic
movement against the skin • Sexual Sensation Remember the mnemonic? J
pronounce it really, really fast… transmission between pain
• Position Sense and Fine Pressure
glutamate!) fibers from pelvis and
• Two –Point Discrimination Dr. Banzuela spinal cord in a patient with
Dorsal Column – for speed, accuracy and precision. Utilizes faster nerve gonorrhea: Substance P
fibers. Antero-lateral System (spinothalamic tract) – slower, less accurate
and precise. Utilizes slower nerve fibers. Look at the examples in the table Tandaan: Substance P is inhibited by Opiods.
Dr. Banzuela
above. SPECIAL NOTES ON PAIN
Dr. Banzuela

MNEMONIC ANTEROLATERAL SYSTEM • Receptors: free-nerve endings that exhibits little or no adaptation
• Triggered by Temp < 15°C or > 43°C
SLAP SOMEONE IN THE FACE REALLY FAST
His head will move in an anterolateral direction. • Referred Pain:
There will be quick decussation of his head. o Due to sharing of 2nd order neurons in the spinal cord of visceral
He’ll feel pain and temperature. pain fibers and skin pain fibers
o Follows the Dermatome rule
Watch the video as you read and highlight the table below on tactile • Endogenous Analgesia System:
receptors:
o NTs include Serotonin, Epi, NE
§ Blocks pain signal at entry point in the spinal cord
TACTILE RECEPTORS
https://qrs.ly/apebgkh

Dr. Banzuela

TACTILE
DESCRIPTION SENSORY ENCODED
RECEPTOR
• Crude touch,
Free Nerve
In the skin temperature and
Endings
pressure
Dendrites encapsulated • Movement of objects
Meissner
in CT and found in non- • low-frequency
Corpuscles
hairy skin (fingertips & (slow) vibration
(FA1)
lips) • determines texture
• Gives steady-state
Expanded tip tactile
signals for
receptor/dendritic
Merkel Disc continuous touch
endings
(SA1) • Localizes touch
Combine to form Iggo
sensation and to
Dome Receptors
determine texture
Hair-end • Movement of object
In hair base
organ on the skin
Enlarged dendritic • Heavy and prolonged
© Topnotch Medical Board Prep
endings with elongated touch (detects
Ruffini Look at the picture of the dermatomes above. In med school, when we were
capsules in deep skin, sustained or STEADY
Corpuscles shown a standing man with dermatomes labeled all over, I used to wonder
internal tissues and PRESSURE) and to why there doesn’t seem to be a regular pattern when it comes to those
(SA2)
joint capsules; signal degree of joint dermatomes – they seemed haphazardly arranged. Later, I realized that
encapsulated rotation the problem was in the presentation of those dermatomes in the books
• Detects deep themselves – in the picture above of a man assuming his original animal-
Unmyelinated dendritic
Pacinian pressure like “four-legged” stance, you will notice that the dermatomes are actually
endings, onion-shaped,
Corpuscles • high-frequency regularly arranged in a regular manner from front to back.
found in subcutaneous Dr. Banzuela
(FA2) (fast) vibration
skin and deep fascia Chemicals and NTs involved in Pain Modulation
• tapping
Merkel and • 2-point • Nucleus Raphe Magnum and Spinal Dorsal Horn: Serotonin
-- • Locus Coeruleus: NE
Meissner discrimination
• Periaqueductal gray matter: Morphine
Found in the epidermis: Merkel Cells(basal layer of epidermis),
Keratinocytes, sweat glands (sweat glands originate from epidermis but
• Spinal Dorsal Horn: Enkephalin
are located in the dermis) • Dorsal Root Ganglion: Opioids
Dr. Banzuela

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VISION
• Refractive Power
o ability to bend light
o measured in Diopters (Reciprocal of focal distance in meters)
• Eye: 59 diopters of refractive power
o 2/3 by the Cornea
§ Fixed refractive power
o 1/3 by the Lens
§ Variable refractive power
§ Held by suspensory ligaments (zonula fibers)

© Topnotch Medical Board Prep

Watch this video to emphasize what you have just read regarding lens,
suspensory ligaments and the circular muscles:
© Topnotch Medical Board Prep

• When Ciliary Muscles are relaxed LENS OF THE EYE


o Increased tension from Suspensory Ligaments https://qrs.ly/d5ebien
o Lens becomes Flat
• When Ciliary Muscles are contracted
Dr. Banzuela
o Decreased tension from Suspensory Ligaments
o Lens becomes Spherical IMPORTANT POINTS VISION
FAR OBJECTS FOCUS: NEAR OBJECTS FOCUS:
Flat Lens Not flat (Spherical) Lens
Normal Vision (20/20 sight): emmetropia (no refractive error)
REFRACTIVE ERRORS
DISORDER DESCRIPTION CORRECTIVE LENSES
Myopia
“Long Eyeball”: light rays converge IN FRONT of the retina Biconcave Lenses
(Near-Sightedness)
Hyperopia
“Short Eyeball”: light rays converge BEHIND the retina Convex Lenses
(Far-Sightedness)
Irregular/Non-uniform Curvature of the Cornea: multiple
Astigmatism Cylindrical Lenses
convergences of light in the retina
Age-Related Loss of Accommodation (>40y/o);
Convex Lenses if initially with 20/20
Presbyopia Presbyopia presents with inability to read newspaper due to
vision
inability to contract: ciliary body

RETINAL CELL FUNCTION NOTES


Pigment Epithelial • Absorb stray light (prevents light scattering) • Involved in macular degeneration, retinal detachment
Cells • Converts 11-cis retinal to all-trans retinal and albinism
Receptors Cells: • Synapses with bipolar cells • Not present in fovea, but has high concentration in
Rods • Sensitive to low-intensity light (night vision) Parafoveal region
• Synapses with bipolar cells
Receptors Cells:
• Sensitive to high-intensity light (day, color • Present in Fovea centralis (area of most acute vision)
Cones
vision)
• Few Cones synapse on single bipolar cells: causes high
• Interneuron between Receptor Cells (Rods,
acuity, low sensitivity of cones
Bipolar Cells Cones) and Ganglion cells
• Many Rods synapse on single bipolar cells: less acuity,
• Contrast Detectors
greater sensitivity
Amacrine, • Interneurons;
--
Horizontal Cells • form local circuits with bipolar cells
Müller Cells • Maintains internal geometry of the retina • Retinal glial cell
• P Cells: Color, Form, Fine Details
• Output cells of the Retina
Ganglion Cells • M Cells: Illumination, Movement
• Axons form optic nerve
• W Cells: Unknown function

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TOPNOTCH MEDICAL BOARD PREP PHYSIOLOGY MAIN HANDOUT BY DR. ENRICO PAOLO C. BANZUELA
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This handout is only valid for October 2023 PLE batch. This will be rendered obsolete for the next batch since we update our handouts regularly.

© Topnotch Medical Board Prep

Tandaan ang favorite sa med school at sa med boards: optic chiasm… heteronymous bitemporal hemianopsia =)
Homonymous hemianopia with macular sparing involve… calcarine fissure
Effect of optic nerve transection: Blindness in the ipsilateral eye
Actually, they can ask any disorder and corresponding sites above. Go through them and memorize.
Visual Field Charting can be done via: Perimetry
Rare disorder characterized by severe periorbital headaches, decreased and painful eye movements (ophthalmoplegia) associated with paralysis of CN III, IV
and/or VI: Tolosa-Hunt Syndrome
Dr. Banzuela

✔GUIDE QUESTIONS
Cutting which structure on the left side causes total blindness in the left eye?
(A) Optic nerve
(B) Optic chiasm
(C) Optic tract
(D) Geniculocalcarine tract 2-9. Costanzo LS. BRS Physiology. 7 ed. 2019
th

Cutting which structure causes blindness in the temporal fields of the


left and right eyes?
(A) Optic nerve
(B) Optic chiasm
(C) Optic tract
(D) Geniculocalcarine tract 2-30. Costanzo LS. BRS Physiology. 7 ed. 2019
th

Cutting which structure on the right-side causes blindness in the


temporal field of the left eye and the nasal field of the right eye?
(A) Optic nerve
(B) Optic chiasm
(C) Optic tract
(D) Geniculocalcarine tract 2-17. Costanzo LS. BRS Physiology. 7 ed. 2019
th

PHYSIOLOGIC BLIND SPOT/BLIND SPOT


• Corresponds to the OPTIC DISC
o Are in the retina with no light sensitive rods or cones © Topnotch Medical Board Prep

§ No image detection Memorize all the steps above since it’s a favorite in any physio exam.
Unique ang vision because hyperpolarization causes the action potential.
o This is also where ganglion cells axons exit the eye to form the
Somethings to help you: remember, ang Vitamin A, CIS muna bago maging
optic nerve TRANS. Metarhodopsin II activates transducin that activates
• Location: 12-15 degrees temporally, 1.5 degrees below the phosphodiesterase. From here on, negative statements na lahat –
horizontal meridian; 7.5 degrees high, 5.5 degrees wide DECREASED cGMP, CLOSED Na+ channels, HYPERPOLARIZATION,
DECREASED glutamate.
Dr. Banzuela
STEPS IN PHOTORECEPTION OF RODS
1. Vitamin A regenerates 11-cis rhodopsin/retinal. ✔GUIDE QUESTION
2. Photons (light particles) converts 11-cis rhodopsin/retinal to Which of the following is a step-in photoreception in the rods?
all-trans rhodopsin/retinal. (A) Light converts all-trans rhodopsin to 11-cis rhodopsin
(B) Metarhodopsin II activates transducin
3. Several intermediates from all-trans rhodopsin are formed. The
(C) Cyclic guanosine monophosphate (cGMP) levels increase
most important: Metarhodopsin II. (D) Rods depolarize
4. Metarhodopsin II activates a Gt or Transducin. Transducin (E) Release of neurotransmitter increases
activates Phosphodiesterase. 2-21. Costanzo LS. BRS Physiology. 7th ed. 2019

5. Phosphodiesterase converts cGMP to 5’GMP decrease cGMP


levels. RECEPTIVE FIELDS OF THE GANGLION CELLS, LATERAL
6. Decreased cGMP causes closure of Na+ channels. This GENICULATE CELLS, VISUAL CORTEX
decreases Na influx leading to hyperpolarization. The brighter • Receptor Cells Connected to Ganglion cells via Bipolar Cells:
the light, the greater the hyperpolarization. forms Center of Receptive Field of the Ganglion Cells
7. Hyperpolarized photoreceptors lead to decreased glutamate • Receptor Cells connected to Horizontal Cells: forms Surround of
8. Decreased glutamate → Excitatory ionotropic glutamate Receptive Field of the Ganglion Cells
receptors in bipolar and horizontal cells are inhibited. • On-Center, Off-Surround is one pattern (center depolarizes,
9. Decreased glutamate → Inhibitory metabotropic glutamate receptors surround hyperpolarizes); opposite pattern can occur; Lateral
in bipolar and horizontal cells are excited and depolarized. Geniculate Cells of the thalamus retains pattern
• Increases when light strikes the eye: activity of transducin

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This handout is only valid for October 2023 PLE batch. This will be rendered obsolete for the next batch since we update our handouts regularly.
• In the Visual Cortex, 3 Cell Types detect shape and orientation of
figures:
CELL DESCRIPTION
• Have center surround and on-off patterns,
Simple Cells elongated rods. Respond to Bars of Light
with correct position and orientation
• Complex Cells: respond to Moving Bars
Complex Cells
or Edges of Light
Hypercomplex • respond to Lines with particular Length
Cells and to curves/angles
✔GUIDE QUESTION © Topnotch Medical Board Prep

Which type of cell in the visual cortex responds best to a moving bar of light?
(A) Simple
(B) Complex
(C) Hypercomplex
(D) Bipolar
(E) Ganglion 2-11. Costanzo LS. BRS Physiology. 7 ed. 2019
th

A mnemonic to help you: Simple Cells: Bars of light Lang. Complex: gumagalaw
na yung bar (Moving Bars). Hypercomplex: yung shape ng bar naging Curved na.
Dr. Banzuela

HEARING
• Sound Frequency: measured in Hertz (Hz)
o Directly correlated with PITCH
o Human ear: 20-20,000 Hz
• Sound Intensity/Pressure: measured in Decibels (dB) © Topnotch Medical Board Prep
o Directly correlated with sound AMPLITUDE (loudness/clarity) Which is affected in sensorineural hearing loss – cochlea, vestibule,
o 60dB: conversational Speech tympanic membrane, external auditory canal?
o 85 dB: limit to prevent Occupational Hearing Loss A: Cochlea (from damaged hair cells inside)
Dr. Banzuela
o >120 dB: causes pain, triggers attenuation reflex (stapedius HEARING
and tensor tympani contract reflexively)
• Sound waves causes cochlea to vibrate → cilia on inner hair cells
EAR bend by shearing force since basilar membrane is stiffer than
• Outer Ear tectorial membrane
o Pinna and external auditory canal o Depolarization of inner hair cells is caused by: K+ going into the
o For sound localization and sound collection cells (since endolymph is rich in K+ compared to ICF)
• Bended cilia on one direction causes depolarization, the opposite
hyperpolarization as it changes K+ conductance → causes
oscillating potential called cochlear microphonic potential
• Outer hair cells characteristics
o Respond to sound like inner hair cells
o Motor protein: Prestin
o Depolarization: shortens outer hair cells
o Hyperpolarization: lengthens outer hair cells
o Damage leads to reduced sound clarity (due to reduced amplitude)
• Place Theory of Hearing:
o Inner hair Cells near BASE (oval and round windows):
respond to high-frequency sounds
© Topnotch Medical Board Prep o Inner hair Cells near Apex (helicotrema): respond to low
• Middle Ear frequency sounds
o Tympanic membrane, auditory ossicles (malleus, incus, • If a patient is unable to hear high-frequency sound, damage is
stapes) that inserts into oval window (membrane between closest to oval window
middle ear and inner ear) Here’s a video discussing the Place Theory of Hearing. Refer to the pictures
o Auditory ossicles amplify sound from large tympanic membrane and readings above:
going into smaller oval window
§ For Impedance matching: sound in air from outer ear is PLACE THEORY
matched with sound in fluid in inner ear OF HEARING
https://qrs.ly/u9ebif8

Dr. Banzuela

✔GUIDE QUESTION
Which of the following statements best describes the basilar membrane
of the organ of Corti?
(A) The apex responds better to low frequencies than the base does
(B) The base is wider than the apex
© Topnotch Medical Board Prep (C) The base is more compliant than the apex
Watch this video explaining attenuation reflex: (D) High frequencies produce maximal displacement of the basilar
membrane near the helicotrema
(E) The apex is relatively stiff compared to the base
ATTENUATION REFLEX 2-6. Costanzo LS. BRS Physiology. 7th ed. 2019
“Apex” is in the helicotrema. “Base” is near the oval and round windows.
https://qrs.ly/6rebif3 Dr. Banzuela

• Central Auditory Pathways


Dr. Banzuela
o Fibers ascend through lateral lemniscus to inferior colliculus to
• Inner Ear medial geniculate nucleus of thalamus to auditory cortex
o Bony labyrinth (semicircular canals, cochlea, vestibule) o Fibers maybe crossed or uncrossed
o Membranous labyrinth (series of ducts) § Lesions of cochlea of one ear: unilateral deafness
o Endolymph is seen in the scala media/cochlear duct § Central unilateral lesions: may not present with unilateral
§ high in potassium deafness due to mixture of ascending auditory fibers from both ears
o Perilymph is seen in the scala vestibuli and scala tympani o (+) tonotropic representation of all frequencies at all levels of
§ high in sodium central auditory pathway
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This handout is only valid for October 2023 PLE batch. This will be rendered obsolete for the next batch since we update our handouts regularly.
VESTIBULAR SYSTEM • Olfactory Epithelium innervated by:
• Allows reflex adjustments of the head, eyes and postural muscles o CN I (Olfactory Nerve): detects scent
to provide stable visual image and steady posture o CN V (Trigeminal Nerve): detects noxious / painful stimuli
• Consists of: (e.g., ammonia)
o 3 Perpendicular Semicircular Canals: detect angular acceleration • Odorant Receptors
o Detects position of head in space: Otolith organs: o Located on neurons in the olfactory epithelium that project to
§ Utricle: detect horizontal (linear) acceleration mitral cells and from there directly to the olfactory cortex
§ Saccule: detect vertical (linear) acceleration • Olfactory memories: found in entorhinal cortex
• Happens when head rotated to the right: both L and R eyes • Cribriform Plate Fracture: damages CN I but not CN V:
deviate towards Left o (+) anosmia but (+) response to ammonia
• Receptors: Hair Cells • MOA:
• Cupula: gelatinous structure o Odorant molecules bind to receptors in the cilia of olfactory
• Kinocilium: single long cilium of hair cell receptor cells
• Stereocilia: smaller cilia of hair cell o Golf are used as transducers to activate cAMP second messenger system
• Rule: o ↑ cAMP opens Na+ channels causing depolarizing receptor potential
o Stereocilia bends towards kinocilium: depolarization o Action potentials are then generated and propagated once
o Stereocilia bends away from kinocilium: hyperpolarization threshold is reached
✔GUIDE QUESTION
Which of the following statements about the olfactory system is true?
(A) The receptor cells are neurons
(B) The receptor cells are sloughed off and are not replaced
(C) Axons of cranial nerve (CN) I are A-delta fibers
(D) Axons from receptor cells synapse in the prepiriform cortex
(E) Fractures of the cribriform plate can cause inability to detect
ammonia 2-23. Costanzo LS. BRS Physiology. 7 ed. 2019
th

TASTE
• Taste Receptors: not true neurons, not synonymous with taste buds
o Taste receptor is a type of chemoreceptor, Innervated by
afferents of CN VII, IX, X
• Anterior 2/3 of tongue: CN VII (Chorda Tympani Facial Nerve)
• Posterior 1/3 of tongue: CN IX (Glossopharyngeal Nerve)
• Back of throat and epiglottis: CN X (Vagus Nerve)
TASTE RESPOND TO
Sweet Sugar
© Topnotch Medical Board Prep Umami Glutamate
✔GUIDE QUESTION Salty Na
Which of the following would produce maximum excitation of the hair Sour Acids
cells in the right horizontal semicircular canal?
(A) Hyperpolarization of the hair cells Bitter Alkaloids
(B) Bending the stereocilia away from the kinocilia All 5 tastes can be detected all throughout the borders of the tongue (the
(C) Rapid ascent in an elevator center of the tongue is relatively “tasteless” due to decreased taste
(D) Rotating the head to the right 2-25. Costanzo LS. BRS Physiology. 7 ed. 2019
th
receptors in there). But particular sites are more sensitive to particular
Mnemonic: where you head turns, is where depolarization happens. In tastes (e.g., tip of the tongue for sweet). Trivia: What is the 6th taste?
the opposite direction, hyperpolarization happens. You turn your head Answer: Fat. We’re all chubby-chasers. =)
to the right, and the stereocilia bends towards the kinocilium, and Taste receptor that detects H+, Enac activation: Sour
Dr. Banzuela
depolarization happens on the right ear.
Dr. Banzuela ✔GUIDE QUESTION
NYSTAGMUS A lesion of the chorda tympani nerve would most likely result in
(A) impaired olfactory function
• Direction is frequently horizontal (i.e., the eyes move in the (B) impaired vestibular function
horizontal plane), but it can also be vertical (when the head is (C) impaired auditory function
tipped sidewise during rotation) or rotatory (when the head is (D) impaired taste function
tipped forward) (E) nerve deafness 2-24. Costanzo LS. BRS Physiology. 7th ed. 2019

• Direction of Nystagmus: same direction as head rotation


TASTE PATHWAY
• Postrotatory Nystagmus occurs in opposite direction of the
• CN VII, CN IX, and CN X → enter medulla → ascend in the solitary
head rotation
tract → terminate on second-order taste neurons in the solitary
o Due to continued movement of endolymph in the semicircular
nucleus → ascend ipsilaterally to the ventral posteromedial
canals, with consequent bending of the cupula and
nucleus of the thalamus → end at the taste cortex
stimulation of hair cells
• Cause of dysgeusia (altered taste) following tooth extraction:
✔GUIDE QUESTION damage to the gustatory afferent nerves
A ballet dancer spins to the left. During the spin, her eyes snap quickly to
the left. This fast eye movement is 2.3 MOTOR SYSTEMS
(A) nystagmus MOTOR UNIT (MU)
(B) Postrotatory nystagmus
(C) ataxia
• Single motoneuron + all the muscle fibers that it innervates
(D) aphasia 2-18. Costanzo LS. BRS Physiology. 7 ed. 2019
th
o Small MU (Small Motoneurons): innervate few muscle fibers
o Large MU (Large Motoneurons): innervate many muscle fibers
Again, nystagmus – same direction as head rotation. Postrotatory
nystagmus, opposite direction.
• Size Principle: Small MU are “recruited first” (fire first) before Big
Dr. Banzuela MU to gradually increase muscle tension
• Small motor units are also called slow (S) motor units (vs. Fast
OLFACTION fatigable (FF motor units)
• Olfactory Neurons • Small Motor Neurons innervate Slow-Twitch fibers (generate
o Only Neurons capable of reproduction (non-permanent cells) smallest force, but able to maintain levels of force for long
periods). Small motor neurons innervate few muscle fibers.
Some board-relevant facts about olfaction (and favorite questions in quiz The definition of motor units, and the “size principle” are important. Small MU
bee competitions): it uses Type C nerve fibers (the slowest, least precise and active first before large MU to make sure that you have muscle contraction that
accurate nerve fiber), it is the only sensory modality that does NOT send starts as weak, and gradually becomes strong (you don’t want the opposite to
fibers to the thalamus (hindi marunong magmano sa thalamus!), and happen – if the opposite occurs, it will mess up your movements).
olfactory neurons are the only neurons capable of reproduction. Dr. Banzuela
Dr. Banzuela

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MUSCLE SENSORS
MUSCLE
NERVE FIBER FUNCTION
SENSOR
Group Ia and II Static and dynamic
Muscle afferents (in changes in muscle length
Spindle parallel with (Mnemonic:
extrafusal fibers) “SpindLLLLLLe, Length”)
Group Ib
Golgi Muscle Tension
afferents (in
Tendon (Mnemonic: “Tendon:
series with
Organs Tension”)
extrafusal fibers)
Group II afferents
Pacinian
(distributed Vibration
Corpuscles
throughout) © Topnotch Medical Board Prep

Free Nerve ✔GUIDE QUESTION


Group III and IV Noxious Stimuli Which of the following is a characteristic of nuclear bag fibers?
Endings
(A) They are one type of extrafusal muscle fiber
Muscle spindles and Golgi tendon are proprioceptors – they are for (B) They detect dynamic changes in muscle length
position sense. Muscle spindles is synonymous with INTRAFUSAL muscle (C) They give rise to group Ib afferents
fibers. Proprioceptors use Type A-alpha fibers – the best, fastest, most (D) They are innervated by α-motoneurons
myelinated, most precise and accurate nerve fibers. They use this type of 2-24. Costanzo LS. BRS Physiology. 7th ed. 2019
nerve fiber because position sense requires speed, accuracy, and precision. Nuclear BAG – dynamic. Nuclear CHAIN – static. Mnemonic: imagine
Muscles involved in fine movements use MORE muscle spindles compared a girl holding a very expensive bag that a thief tries to steal in broad
to muscles that are used for coarse movements/posture. daylight. Hinampas ni girl si thief using the bag. Yung act ng
Dr. Banzuela paghampas – DYNAMIC. Afterwards, dumating yung police, ang they
MOA OF MUSCLE SPINDLE (INTRAFUSAL FIBERS) tied up the thief using CHAINS. Hindi makagalaw yung thief – STATIC.
Dr. Banzuela
1. When muscle is stretched, muscle spindle also stretched
2. This stimulates Group I and Group II afferent Fibers of the STRETCH REFLEX
Muscle Spindle • Muscle that was stretched will contract along with Synergistic
3. This stimulates Alpha Motoneurons that innervates extrafusal muscles; Antagonistic Muscles will relax
muscle fibers → causes appropriate muscle contraction and • Patellar Knee Jerk Reflex: tapping patellar tendon → quadriceps
shortening stretch → Muscle Spindles activated → Group Ia afferent
4. Gamma Motoneurons that innervate muscle spindles are also activated → Alpha motoneurons activated → quadriceps contract
co-activated to adjust sensitivity of muscle spindle during ✔GUIDE QUESTION
muscle contraction Muscle stretch leads to a direct increase in firing rate of which type of
5. When dynamic Gamma Motoneurons are activated at the nerve?
same time as Alpha Motoneurons, the number of spindle 1a (A) α-Motoneurons
afferents impulses is greater than when alpha discharge (B) γ-Motoneurons
alone is increased. (C) Group Ia fibers
(D) Group Ib fibers From Physiology BRS, 6th Ed
MNEMONICS: MUSCLE SPINDLE
AEGIS:
Alpha-Extrafusal,
Gamma-Intrafusal,
S-basta may “S” para macomplete yung mnemonic =)
Again, with feelings, AEGIS. J
Dr. Banzuela

• Most important role of Gamma Motoneurons: maintain 1a


afferent activity during muscle contraction

TYPES MUSCLE SPINDLE (INTRAFUSAL FIBERS)


NUCLEAR BAG NUCLEAR CHAIN
FIBERS FIBERS
Detect Dynamic Detect Static
Function
changes changes
Sensory Fiber Group Ia Afferents Group II Afferents
Arrangement of Central “Bag”
In rows
Nuclei region

© Topnotch Medical Board Prep


MUSCLE REFLEXES
REFLEX # OF SYNAPSES STIMULUS AFFERENT FIBERS RESPONSE
Stretch Reflex also called
MYOTATIC REFLEX or Monosynaptic Muscle is stretched Ia Contraction of the muscle
KNEE-JERK REFLEX
Clasp-Knife Reflex also
called GOLGI TENDON
Disynaptic Muscle contracts Ib Relaxation of the muscle
REFLEX or INVERSE
STRETCH REFLEX
Flexor-Withdrawal Reflex Ipsilateral flexion;
Polysynaptic Pain II, III, IV
(after touching a hot stove) contralateral extension
Be careful – they like to use synonyms for questions involving these reflexes (e.g., Stretch Reflex = Myotactic Reflex = Knee Jerk Reflex. Golgi Tendon Reflex
= Clasp Knife Reflex = Inverse Stretch Reflex. Flexor-Withdrawal Reflex = Flexor-Extensor Reflex.)

Other example of Monosynaptic Reflex: Achilles Tendon Reflex


Other examples of Polysynaptic Reflex: Pupillary Reflex, Corneal Reflex
Muscle that contracts during knee-jerk reflex/patellar reflex: Quadriceps femoris (extensor muscle)
In flexor-withdrawal reflex, stronger stimuli will produce greater flexion and shorter reaction times that may lead to AFTER-DISCHARGE (prolonged, repeated
firing of the motor neurons producing series of movements). Favorite yang flexor-withdrawal reflex na yan – remember that it is a reflex involving flexion on
ipsilateral side and extension on contralateral side
Dr. Banzuela

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✔GUIDE QUESTIONS CORTICOSPINAL (PYRAMIDAL) TRACT
Which reflex is responsible for monosynaptic excitation of ipsilateral Motor cortex
homonymous muscle? • downward the brain stem, forming the pyramids of the medulla
(A) Stretch reflex (myotatic)
(B) Golgi tendon reflex (inverse myotatic)
• Most important output pathway from the motor cortex:
(C) Flexor withdrawal reflex Corticospinal tract (pyramidal tract). Fibers originate from
(D) Subliminal occlusion reflex 2-10. Costanzo LS. BRS Physiology. 7 ed. 2019 th giant pyramidal cells (Betz cells)
Which reflex is responsible for polysynaptic excitation of contralateral • fibers cross in the lower medulla to the opposite side and descend
extensors? into the lateral corticospinal tracts (80%)
(A) Stretch reflex (myotatic) o cortical control of the movement of an entire limb
(B) Golgi tendon reflex (inverse myotatic) • Few fibers do not cross to the opposite side in the medulla but
(C) Flexor withdrawal reflex
pass ipsilaterally down the cord in the ventral/anterior
(D) Subliminal occlusion reflex 2-24. Costanzo LS. BRS Physiology. 7 ed. 2019 th

corticospinal tracts (20%)


NERVE LESIONS COMMON HAND PRESENTATIONS o concerned with control of bilateral postural movements by
HAND PRESENTATION NERVE INVOLVED the supplementary motor cortex
Claw Hand Ulnar nerve Provides pattern of motor activity: Primary motor area, premotor
Wrist Drop Radial nerve area, basal ganglia
“Hand of Benediction” Dr. Banzuela
Median nerve
or “Ape Hand”

VOLUNTARY MOTOR MOVEMENTS


• Originate in the Cerebral Cortical Association Areas

© Topnotch Medical Board Prep


MOTOR CENTERS AND PATHWAYS
• Pyramidal Tracts: corticospinal and cortical bulbar tracts that
passes through medullary pyramids
o Essential for voluntary movement: precentral gyrus,
corticospinal, corticobulbar tracts
• Extrapyramidal Tracts: motor pathways that originate in
following brainstem structures: © Topnotch Medical Board Prep
CORTICOBULBAR TRACT
DISTRIBUTION ACTIONS
• tract arises primarily from areas of the motor cortex related to
From Red Nucleus to
Rubrospinal Stimulates flexors, the head and face
interneurons of
Tract Inhibits extensors • Descending motor pathway that terminates in the pons and
lateral SC
medulla
Stimulates both
• Cranial equivalent of the corticospinal tract
Pontine flexors and
From Pons to • Responsible for voluntary movement of cranial muscles
Reticulospinal extensors
ventromedial SC Oh I Olfactory SEnsory
Tract (mainly
extensors) Oh II Optic SEnsory
From Medullary Oh III Oculomotor MOtor
Inhibits both To IV Trochlear MOtor
Medullary Reticular Formation
flexors and Touch V Trigeminal MIxed
Reticulospinal to SC interneurons in
extensors And VI Abducens MOtor
Tract the intermediate
(mainly extensors) Feel VII Facial MIxed
gray area
From Deiters nucleus Very VIII Vestibulocochlear Sensory
Lateral Inhibits Flexors, Good IX Glossopharyngeal MIxed
to ipsilateral
Vestibulospinal Stimulates Velvet X Vagus MIxed
motoneurons and
Tract extensors
interneurons A… XI Accessory MOtor
From Superior (Spinal)
Tectospinal Controls neck
Colliculus to cervical H… XII Hypoglossal MOtor
Tract muscles
SC

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© Topnotch Medical Board Prep © Topnotch Medical Board Prep

RUBROSPINAL TRACT VESTIBULOSPINAL TRACT (MEDIAL)


• Originates in the red nucleus in the midbrain • arises in the medial vestibular nucleus
• projects to the spinal cord interneurons and alpha motor neurons • terminates on LMN circuit neurons of cervical and upper thoracic
• Stimulate flexor muscles levels
• inhibits the activity of extensor muscles o controlling the neck muscles (tandem with corticobulbar
tract)
RETICULOSPINAL TRACT
o stabilizing the head
• Pontine Reticulospinal Tract o coordinating head movements with eye movements
o Arises from nuclei in the medial pontine reticular formation
o projects to the ventromedial motor neurons of the spinal cord VESTIBULOSPINAL TRACT (LATERAL)
o Stimulate flexors and (primarily) extensor muscles
• arises in the lateral vestibular nucleus
Predominates the medullary counterpart
• Stimulate extensor muscles
• Medullary Reticulospinal Tract
o Arises from the medullary reticular formation, • Inhibits flexor
o projects to motor neurons in the lateral spinal cord • serves to mediate postural adjustments
o Counterbalances the pontine reticular system and inhibits
the extensors of the body TECTOSPINAL TRACT
• originates in the superior colliculus of the midbrain
Characterizes the corticorubrospinal system: Serves as an accessory route
for transmission of discrete signals, ends on the interneurons and motor • project to the cervical spinal cord
neurons that control the more distal muscles of the limbs, stimulation of a • innervate motor neurons responsible for neck movements
single point in a portion of the red nucleus will cause contraction of a single • responsible for orienting the head and neck during eye
muscle, humans have small and rudimentary red nucleus movement
Dr. Banzuela

© Topnotch Medical Board Prep


DECORTICATION VS. DECEREBRATION EFFECT OF TRANSECTIONS: AT THE SC
• Paraplegia: loss of voluntary movements below level of lesion
• Loss of conscious sensation below level of lesion
• Spinal Shock (Absent reflexes)
o Limbs flaccid, reflexes absent immediately after
transection. Partial recovery may occur after sometime (e.g.
after several hours to a few weeks)
§ reflexes are NOT chronically suppressed after spinal cord
transection
o C7 transection: HR and BP decreases
o C3 transection: breathing stops
o C1 transection: death
EFFECT OF TRANSECTIONS: ABOVE SC
• Lesions above Lateral Vestibular Nucleus: decerebrate rigidity
• Lesions between Pontine Reticular Formation and Midbrain:
decerebrate rigidity
o Decerebrate rigidity is spasticity due to facilitation of myotactic
stretch reflex
• Lesions above Red Nucleus: decorticate posturing and intact
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tonic neck reflexes
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✔GUIDE QUESTIONS BASAL GANGLIA
The excessive muscle tone produced in decerebrate rigidity can be • Consists of striatum, globus pallidus, subthalamic nuclei and
reversed by substantia nigra
(A) stimulation of group Ia afferents
(B) cutting the dorsal roots
• Modulates thalamic outflow to motor cortex to plan and execute
(C) transection of cerebellar connections to the lateral vestibular nucleus smooth movements
(D) stimulation of α-motoneurons • Primary function of basal ganglia is the planning and
(E) stimulation of γ-motoneurons 2-14. Costanzo LS. BRS Physiology. 7 ed. 2019 th programming of movement
Complete transection of the spinal cord at the level of T1 would most • Main NT: GABA
likely result in • NT between striatum and substantia nigra: Dopamine
(A) temporary loss of stretch reflexes below the lesion o Inhibits the inhibitory indirect pathway using D2 receptors
(B) temporary loss of conscious proprioception below the lesion
(C) permanent loss of voluntary control of movement above the lesion
o Stimulates the excitatory direct pathway using D1 receptors
(D) permanent loss of consciousness above the lesion • Subthalamic Nucleus: releases Glutamate → excites globus
2-28. Costanzo LS. BRS Physiology. 7th ed. 2019 pallidus, internal segment
CEREBELLUM • Substantia Nigra Parts Reticulata → releases GABA → inhibits
• Functions: thalamus
o Vestibulocerebellum: for control of balance and eye movements • Substantia Nigra Pars Compacta → releases Dopamine →
o Pontocerebellum: for planning and initiation of movement inhibit the striatum
o Spinocerebellum: for synergy (controls rate, force, range, • Striatum → releases ACh → inhibit substantia nigra pars
direction of movement) reticulata
• Clinical Conditions associated with cerebellar dysfunction: • Globus Pallidus External Segment → releases GABA → inhibit
o Ataxia: lack of muscle coordination that includes delay in subthalamic nucleus
initiation, poor execution of movement sequence and failure to • Lesions:
perform rapid alternating movements (dysdiadochokinesia) o Globus Pallidus: inability to maintain posture
o Intention Tremor: low frequency tremor (<5 Hz) whose o Subthalamic Nucleus: wild, flailing movements
amplitude of increases as an extremity approaches the endpoint (hemiballismus)
of deliberate and visually guided movement o Striatum: quick, continuous, uncontrollable movements (e.g.
o Absent Rebound Phenomenon: failure of antagonistic muscle in Huntington disease)
to contract after removal of resistance to limb movement o Substantia nigra: Tremors, cogwheel Rigidity, reduced
voluntary movement (Akinesia), Postural problems
When you hear the word “cerebellum”, I want you to think of two things:
Ataxia and Dysdiadochokinesia. (Mnemonic: “T-R-A-P” of Parkinson Disease)
Dr. Banzuela § in Parkinson there is continued degeneration of the
✔GUIDE QUESTIONS dopaminergic neurons of the Substantia Nigra
Which of the following structures has a primary function to coordinate
rate, range, force, and direction of movement?
(A) Primary motor cortex
(B) Premotor cortex and supplementary motor cortex
(C) Prefrontal cortex
(D) Basal ganglia
(E) Cerebellum 2-31. Costanzo LS. BRS Physiology. 7 ed. 2019 th

The inability to perform rapidly alternating movements (dysdiadochokinesia) is


associated with lesions of the:
(A) premotor cortex
(B) motor cortex
(C) Cerebellum
(D) substantia nigra
(E) medulla 2-26. Costanzo LS. BRS Physiology. 7 ed. 2019 th

• Layers of the Cerebellar Cortex (from innermost to outermost) © Topnotch Medical Board Prep

1. Granular Layer: contains granule cells, Golgi Type II cells, glomeruli MOTOR CORTEX
2. Purkinje Cell Layer: contains Purkinje Cells • Pre-Motor Cortex and Supplementary Motor Cortex (BA 6)
§ Only output of the cerebellar cortex o Function: Generates movement plan
§ Output are always inhibitory, using GABA § This is then transferred to primary motor cortex for execution
§ Output projects to deep cerebellar nuclei and to the o Supplementary motor cortex: rehearses complex motor
vestibular nucleus sequences
§ Modulates output of cerebellum and regulates rate, range and • Primary Motor Cortex (BA 4)
direction of movement (synergy) o Function: Executes movement
3. Molecular Layer: contains stellate and basket cells, dendrites of § this is then transferred to the brainstem and spinal cord
Purkinje and Golgi Type II cells, parallel fibers (axons of granule cells) where lower motoneurons causes voluntary movements
NEURAL CONNECTIONS IN THE CEREBELLUM o Epileptic event here causes Jacksonian seizures (focal partial
• Granule Cell (GC): releases Glutamate → excite basket cells and seizure)
stellate cells ✔GUIDE QUESTION
• Basket Cells (BC): releases GABA → inhibit Purkinje Cells Which of the following parts of the body has cortical motoneurons with
• Climbing and mossy fiber inputs → exert strong excitatory effect the largest representation on the primary motor cortex (area 4)?
on Purkinje Cells (A) Shoulder
• Purkinje Cells: releases GABA → inhibit deep cerebellar nuclei (B) Ankle
(C) Fingers
• Golgi Cells à excited by mossy fiber collaterals (D) Elbow
(E) Knee 2-15. Costanzo LS. BRS Physiology. 7 ed. 2019
th

CLINICAL CORRELATES
• Brown-Sequard Syndrome
o Caused by functional hemisection of the spinal cord
o (+) contralateral loss of pain and temperature sensation
beginning 1-2 segments below the lesion
o (+) ipsilateral weakness and spasticity in certain muscles
groups
• Amyotrophic Lateral Sclerosis (ALS) or Lou Gehrig Disease
o (+) Degeneration & loss of motor neurons in the motor
cortex, spinal cord, brain stem & corticospinal tract
o Does NOT usually affect sensation
BC – Basket Cell; GC – Golgi Cell; GR – Granule Cell; NG – Cell in deep nucleus;
(+) – excitatory; (-) – inhibitory o May present with UMN or LMN SSx depending on location
© Topnotch Medical Board Prep

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CLINICAL CORRELATES RAPID EYE MOVEMENT
SLOW-WAVE SLEEP
• Patients with Transected Spinal Cords (REM) SLEEP
(NREM SLEEP)
o Have negative nitrogen balance as they catabolize large (PARADOXICAL SLEEP)
amounts of body protein because they are paralyzed below • More difficult to arouse by
the level of transection sensory stimuli
• Difficult to arouse by
• Trinucleotide Repeat Diseases • (REM sleep presents with:
sensory stimuli
o Include Fragile X, Spinocerebellar ataxia type 3, Huntington periods of loss of skeletal
Disease, Friedreich Ataxia muscle tone or atonia)
• Stages:
1 – Alpha waves interspersed
2.4 HIGHER FUNCTIONS OF THE CEREBRAL with Theta waves
CORTEX 2 – Theta waves interrupted by
Sleep Spindles (12-14 Hz) and
EEG WAVES • Beta waves
K+ complexes (large, slow
• Made up of alternating excitatory and inhibitory synaptic potentials)
potentials in the pyramidal cells of the cerebral cortex 3 – Delta waves interrupted by
• Cortical Evoked Potential: changes in the ECG that reflect synaptic Sleep Spindles
potentials evoked in large number of neurons 4 – Delta waves alone
• Gamma Rhythm (30-80Hz) in the EEG maybe a mechanism to
Again: Occurs in REM sleep: Dreams, miosis, erection, occurs every 90
“bind” together diverse sensory information into a single minutes of slow-wave sleep, rapid eye movements, difficult to arouse
percept and action Dr. Banzuela

• Absence seizures are generalized nonconvulsive seizures with SPECIAL NOTES: SLEEP
spike-and-wave discharge in the EEG • Young Adults: 25% REM Sleep
• Disappears when a patient’s eye is open: Alpha rhythm/waves • Newborns: 50% REM Sleep
• Decreases duration of REM sleep
o Age, Alcohol, Benzodiazepines, Amphetamine
• From NREM to Awake state:
o Increase in: Norepinephrine, Serotonin, Histamine
o Decrease in: Acetylcholine, GABA
• Narcolepsy characteristics
o Starts with REM rather than NREM sleep
o Associated with Class II antigen of MHC on Chromosome 6
o Fewer hypocretin (orexin)-producing neurons

LANGUAGE
• Corpus Callosum: for interhemispheric communication
• R Cerebral hemisphere:
o NON-DOMINANT or REPRESENTATIONAL hemisphere in most
Right-handed people
o dominant in facial expression, intonation, body language, spatial
© Topnotch Medical Board Prep
task
Unfortunately, typos are sometimes present in the med boards according
to student feedback. So, if you are asked “What waves are seen in an ECG • Left Cerebral hemisphere: usually dominant in language;
of a person with eyes closed but awake?”, you must deduce that this is typo, lesions here causes aphasia
and that they are referring to an EEG instead of an ECG. Don’t lose your o DOMINANT or CATEGORICAL hemisphere in most R-handed
marbles over them. =) people
Dr. Banzuela
o usually dominant in language; lesions here causes aphasia
SLEEP
§ Wernicke Aphasia: receptive aphasia – “can say, but can’t
• Due to an active inhibitory process and not merely due to fatigue understand” (Mnemonic: “Wordy Wernicke”)
of reticular activating systems § Broca Aphasia: expressive aphasia – “can understand, but
o Possible cause: secretion of Muramyl Peptide cannot say” (Mnemonic: “Broken <speech> Broca”)
Here’s an audio recording discussing brain waves and Sleep Types: A very important message regarding Wernicke Aphasia =):

SLEEP AND
BRAIN WAVES WERNICKE APHASIA
https://qrs.ly/omebifp https://qrs.ly/dmebifx

Dr. Banzuela
Dr. Banzuela

RAPID EYE MOVEMENT CLINICAL CORRELATES


SLOW-WAVE SLEEP
(REM) SLEEP Damage to:
(NREM SLEEP)
(PARADOXICAL SLEEP) • Angular Gyrus in the categorical hemisphere: Anomic Aphasia
• With Active Dreaming; • Inferior parietal lobule (a region in the posterior part of the
• Usually dreamless or
• occurs every 90 minutes of parietal lobe that is close to the occipital lobe): unilateral
unremembered dreams
slow-wave sleep attention and neglect
• ↑ brain metabolism, • Parietal Lobe of the representational hemisphere: Astereognosis
• ↓ muscle tone, (inability to recognize objects by feeling them) and Agnosia
• (+) 10-30% ↓ Blood
• Pupillary constriction, • Mamillary bodies: loss of recent memory
Pressure (BP), Heart Rate
• Active body movements, • Cholinergic neurons in the nucleus basalis of Meynert and related
(HR) and Basal Metabolic
• Irregular BP, HR, Respiratory areas of the forebrain: loss of recent memory
Rate (BMR);
Rate (RR);
• ↑ in GI motility • Penile erection
• Rapid eye movements

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© Topnotch Medical Board Prep

MEMORY SPECIAL NOTES ON MEMORY


• Explicit / Declarative Memory: “Knowing what” • Neocortical Areas: for remote memories
• Implicit Memory: “Knowing How” • Prefrontal Cortex: for working memory
• Short-Term Memory: lasts minutes, involve mere chemical • Inferior Temporal Lobe: for ability to recall faces and forms
change • Amygdala: for production of inappropriate emotional
o Working Memory: keeps info available while individual plans responses when recalling events of the recent past
actions based on it
• Long-Term Memory: resistant to disruption, lasts for a lifetime
2.5 BLOOD-BRAIN BARRIER (BBB) AND
CEREBROSPINAL FLUID (CSF)
BLOOD-BRAIN BARRIER
• Consists of:
o Endothelial cells of cerebral capillaries (and the tight
junctions between them)
o Astrocyte foot processes
o Choroid plexus epithelium
• Functions:
o Maintain constant environment for neurons
© Topnotch Medical Board Prep o Prevents escape of neurotransmitters
o Drugs penetrate BBB to various degrees (easier if lipid-soluble
and nonionized)
• Exists in all areas of the brain EXCEPT in Circumventricular
Organs (CVOs)
o Some areas of the Hypothalamus (including neurohypophysis)
o Pineal gland
o Area Postrema
CSF
• CSF in brain: 150 mL
• CSF produced per day: 500 mL
o 70% by Choroid Plexus
o 30% by Brain Parenchyma
• Functions: Cushioning, buoyancy, maintain normal CNS volume
• Composition approximately the same as interstitial fluid but
differs from blood
o CSF < BLOOD: Glucose, Protein (negligible in CSF), Cholesterol
(negligible in CSF)
o CSF > BLOOD: Na+
o CSF = BLOOD: Osmolarity
CSF is isotonic to blood because even if CSF has higher Na+ concentration,
SPECIAL NOTES ON MEMORY blood has higher protein concentration. This is based on Berne and Levy.
Iba nakasulat sa Physio BRS. We follow Berne and Levy regarding this one.
• Consolidation: conversion of short-term to long-term memory Dr. Banzuela

o Rehearsal, Sleep, Adequate Nutrition (especially Vit B) ✔GUIDE QUESTION


promotes consolidation Which of the following has a much lower concentration in the
• Temporal Lobe: where memory is mainly stored cerebrospinal fluid (CSF) than in cerebral capillary blood?
• Hippocampus: (A) Na+ (D) Protein
o helps ENCODE events of the recent past into long-term (B) K+ (E) Mg2+
2-19. Costanzo LS. BRS Physiology. 7 ed. 2019
memory (C) Osmolarity th

o promotes memory formation when reward and punishment


2.6 TEMPERATURE REGULATION
centers are stimulated
§ Reward Center: Medial Forebrain Bundle (Mnemonic REGULATION OF BODY TEMPERATURE
“MEDIAL as Reward”) • Center for thermoregulation: Hypothalamus
§ Punishment Center: Central Gray Area surrounding the o Sensors: Temperature sensors in skin and hypothalamus
Aqueduct of Sylvius (Mnemonic: Remember 50 Shades of o Detected Temperature compared with Set-point Temperature
Grey – “Punishment from Mr. Grey! Hwapishhh!!! J) § Detected Temp < Set-Point Temp: Initiate Heat Generating
• Thalamus: helps RECALL memory Mechanisms
§ Detected Temp > Set-Point Temperature: Initiate Heat Loss
Remember: hippocampus is NOT for memory storage (memory is stored Mechanisms
throughout the brain but mainly in the temporal lobe). Hippocampus
helps ENCODE or form new memory. Thalamus meanwhile helps you • Heat-Generating Mechanisms
RECALL previously-formed memories. Destroying your hippocampus o Shivering, Thyroid Hormone production, decreased sweating,
would cause ANTEROGRADE amnesia (cannot form new memories). piloerection, skin (cutaneous) vasoconstriction (𝛼1), brown fat
Destroying your thalamus would cause RETROGRADE amnesia (cannot in babies (𝜷3)
recall old memories). • Heat Loss Mechanisms
Dr. Banzuela
o Radiation, Sweating, Skin (cutaneous) Vasodilatation,
Decreased Heat Production
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Main mechanism for heat conservation/heat gain: SHIVERING (behavioral • Pulmonic Circulation, compared to Systemic Circulation, has:
change). Main mechanism for heat loss: RADIATION (60%). o Lower resistance, afterload, stroke work
Other mechanisms for heat loss: evaporation (22%), conduction to air o Same preload, heart rate, stroke volume, cardiac output
(15%), conduction to objects (3%).
• Blood flow per 100g of tissue is greatest in the KIDNEYS
Heat loss that occurs when ambient temperature increases: evaporation
of sweat.
Dr. Banzuela ✔GUIDE QUESTIONS
SPECIAL NOTES ON TEMPERATURE REGULATION Cardiac output of the right side of the heart is what percentage of the
• Anterior Hypothalamus: for heat loss cardiac output of the left side of the heart?
(A) 25% (D) 100%
• Posterior Hypothalamus: for heat gain
(B) 50% (E) 125%
Some mnemonics. think of yourself fanning the anterior part of the body. 3-40. Costanzo LS. BRS Physiology. 7 ed. 2019.
(C) 75% th

ANTERIOR hypothalamus: heat loss. Think of yourself placing on a jacket


And what is the reason for the answer? =) Because once again: CO of the
to keep yourself warm. You first place that jacket on the posterior part of
L heart should be equal to the CO of the R heart.
the body. POSTERIOR hypothalamus: heat gain/preservation. Dr. Banzuela
Dr. Banzuela
In which of the following situations is pulmonary blood flow greater than
• Fever aortic blood flow?
o MOA: Pyrogens → ↑ IL-1 (alpha and beta), IL-6 → ↑ PGE2 → (A) Normal adult
↑set-point temperature in hypothalamus → causes heat- (B) Fetus
generating mechanisms (C) Left-to-right ventricular shunt
o ASA: inhibits COX → ↓ PGE2 → ↓ set-point temp (D) Right-to-left ventricular shunt
o Steroids: inhibits release of arachidonic acid from brain (E) Right ventricular failure 3-18. Costanzo LS. BRS Physiology. 7 ed. 2019. th

phospholipids → ↓ PGE2 → ↓ set-point temp


• *PGE1: keeps ductus arteriosus open. COMPONENTS OF THE CIRCULATION
• PGE2: increases set-point temp. Listen to the audio recording while reading the next table on various vessels:
• Mnemonic: PGE1 – “PGE1: E1 mong bukas ang ductus arteriosus.
PGE2: E2 ang para sa fever!” (fine print: technically, PGE2 can also keep BLOOD VESSELS
the ductus arteriosus open. Use the mnemonic as a rough guide)
https://qrs.ly/emebigb
✔GUIDE QUESTION
Pathogens that produce fever cause _________.
Dr. Banzuela
(A) decreased production of interleukin-1 (IL-1)
(B) decreased set-point temperature in the hypothalamus
(C) shivering DESCRIPTION VESSEL
(D) vasodilation of blood vessels in the skin • Control Conduits
2-22. Costanzo LS. BRS Physiology. 7th ed. 2019
• may rapidly dilate and constrict
• Heat Exhaustion: excessive sweating that decreases BP and ARTERIOLES
• (+) site of greatest resistance, 𝛂1-
causes syncope Vasoconstricts; 𝜷2-Vasodilates
• Heat Stroke: high body temperature that causes tissue damage; • Contains stressed volume
sweating is impaired which further increases temperature; maybe lethal ARTERIES
• high pressure
• Hypothermia: when ambient temperature is so low, that core • Largest total cross-sectional area
temperature cannot be maintained at set-point
• has endothelial cells only
• Malignant hyperthermia (MH): overexcitation of skeletal
• has slowest blood flow velocity CAPILLARIES
muscles due to defective ryanodine receptors (that results in
• metarterioles and pre-capillary sphincters
excess Ca2+ release from SR). Triggers of MH:
control blood flow
o Halothane (also: inhaled general anesthesia, desflurane,
• a.k.a. Capacitance Vessels
enflurane, ether, isoflurane, sevoflurane)
o Succinylcholine • 64% of blood found here, with one-way VEINS
o Heat stress valves
o Vigorous exercise • Drains proteins and fluids from the
LYMPHATIC
• Treatment of MH: Dantrolene, a Ca2+-channel (ryanodine interstitium, carries chylomicrons and
VESSELS
receptor) blocker and muscle relaxant involved in immunity and cancer
Electrolyte involved in malignant hyperthermia: CALCIUM Look at the illustration at the next page. Let’s tackle the basics. “Blood and
Dr. Banzuela air will always flow from high pressure to low”. Remember that dictum. So,
if you want blood to flow from arteries to capillaries to veins, saan
3. CARDIOVASCULAR PHYSIOLOGY pinakamababa ang pressure? Answer: sa veins (NOT the capillaries). All
1. Circuitry of the 6. Regulation of BP veins will eventually drain into the vena cava and then to the right atrium.
Cardiovascular System 7. Microcirculation and Lymph That’s why pressure is lowest sa Right Atrium – around 0-4mmHg. Since all
2. Hemodynamics 8. Special Circulation veins will drain into the Right Atrium, we call right atrial pressure by
3. Cardiac Electrophysiology 9. Gravity, Exercise, another name, we call it Central Venous Pressure (you can think of the right
4. Cardiac Output Hemorrhage atrium as the “central vein” since all veins drain through it eventually).
5. Cardiac Cycle From the R atrium, blood will flow to the R ventricle (after passing through
tricuspid). From R ventricle it will go to the pulmonary artery →
3.1 CIRCUITRY OF THE CARDIOVASCULAR SYSTEM pulmonary arterioles → pulmonary capillaries → pulmonary veins → L
atrium (passing through mitral valve) → L ventricle (passing through
Listen to this audio recording about CO and VR while reading the next
aortic valve) → aorta → systemic arteries → systemic arterioles → systemic
passages:
capillaries → veins.
Remember: site of highest oxygenation: pulmonary vein (100%
CARDIAC OUTPUT oxygenated). Only arteries that contain deoxygenated blood: pulmonary
AND VENOUS RETURN artery and umbilical artery. Only veins that contain oxygenated blood:
https://qrs.ly/eeebig4 pulmonary vein and umbilical vein.
Dr. Banzuela

Dr. Banzuela
✔GUIDE QUESTION
IMPORTANT PRINCIPLES
The greatest pressure decrease in the circulation occurs across the
• Cardiac Output (CO) arterioles because
o CO = HR x SV = VR (A) they have the greatest surface area
§ where HR is heart rate, SV is stroke volume, VR is venous (B) they have the greatest cross-sectional area
return (C) the velocity of blood flow through them is the highest
o CO LEFT (L) Heart = CO RIGHT (R) Heart (D) the velocity of blood flow through them is the lowest
§ CO L Heart: Systemic Blood Flow (E) they have the greatest resistance . 3-32. Costanzo LS. BRS Physiology. 7 ed. 2019
th

§ CO R Heart: Pulmonary Blood Flow At which site is systolic blood pressure the highest?
(A) Aorta (D) Right atrium
o At rest: 5L/min
(B) Central vein (E) Renal artery
o Max CO (Non-Athlete): 20L/min (C) Pulmonary artery 3-3. Costanzo LS. BRS Physiology. 7 ed. 2019.
th

o Max CO (Athlete): 30L/min

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✔GUIDE QUESTION ATRIA
Bakit hindi aorta eh aorta pinakamalapit sa L ventricle? The reason • Primer pumps of the ventricles.
for this → when blood moves from aorta to a branch of that aorta, the • 80% of the blood flows from atria to the ventricles before the
change in direction of blood will hit the branching points and increase atria contracts. Atrial contraction is responsible for 20%
the pressure slightly. Kaya yung branch point ng aorta (among the
ventricular filling
choices above, only renal artery is a branch of the aorta) sa renal artery
mas mataas ang pressure nyan compared sa aorta itself. Analogy: • Not necessary in the resting state since heart pumps 300-400%
imagine driving a very fast car along EDSA. Then you made a sudden more blood than is required at rest
left turn in one of the side streets and hit the gutter. Mataas ang • Becomes an issue only during exercise – atrial damage may lead
pressure ngayon dun sa branch points ng EDSA papunta sa side street. to shortness of breath
Message me on FB messenger if you have a hard time with this so I can
Note that most cases of patient recovery from coronary occlusion is due to
explain better.
Dr. Banzuela presence of collateral vessels.
Dr. Banzuela

© Topnotch Medical Board Prep

3.2 HEMODYNAMICS Must-know yung Ohm’s law ha. Blood flow (Q) is directly proportional to
pressure, inversely proportional to resistance. Blood flow to the entire body
BLOOD FLOW VELOCITY is CO. Resistance to this CO is TPR. Ergo, CO=BP/TPR or rearranged, BP
• Fastest: aorta = CO x TPR (the classic cardio physio formula that you encountered in
• Slowest: capillaries (because of medical school). That formula is based on Ohm’s law (Ohm’s law btw, if
large total cross-sectional area) you remember your high school physics, is more commonly expressed as I =
• Blood Flow Velocity is V/R, where I is current, V is voltage and R is resistance)
Dr. Banzuela
INVERSELY PROPORTIONAL to
✔GUIDE QUESTION
total cross-sectional area
An increase in arteriolar resistance, without a change in any other
component of the cardiovascular system, will produce
(A) a decrease in total peripheral resistance (TPR)
(B) an increase in capillary filtration
(C) an increase in arterial pressure
(D) a decrease in afterload 3-27. Costanzo LS. BRS Physiology. 7 ed. 2019.
th

Listen to this audio recording while reading Poiseuille Law and the
subsequent guide question that follows:

POISEUILLE LAW
© Topnotch Medical Board Prep
https://qrs.ly/6sebigu
BLOOD FLOW
• Directly proportional to Pressure Difference Dr. Banzuela

• Inversely proportional to resistance RESISTANCE TO BLOOD FLOW


• Based on Ohm’s Law: • Based on Poiseuille Law (pronounced as “Pwa-zweeh”)

• Remember: blood viscosity = hematocrit


* this is where we derive the formula BP = CO x TPR o Polycythemia: increased resistance
** Based on Ohm's Law, Pulmonary vascular resistance is (Pulmonary Artery • If a vessel radius decreases: highly increases resistance
Pressure - L Atrial Pressure) over Cardiac Output o Important when it comes to the control conduits arterioles
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✔GUIDE QUESTION BLOOD PRESSURE AT DIFFERENT POINTS
A 53-year-old woman is found, by arteriography, to have 50% narrowing
of her left renal artery. What is the expected change in blood flow
through the stenotic artery?
(A) Decrease to 1⁄2 (D) Decrease to 1⁄16
(B) Decrease to 1⁄4 (E) No change
3-1. Costanzo LS. BRS Physiology. 7 ed. 2019.
(C) Decrease to 1⁄8 th

Radius = ½ its original value


Resistance = 8ηl/π ½)4
= 16x its original value
new Q =ΔP/16R
The new Q will be 1/16 its original value
Favorite yang 1/16 na yan for some weird reason. 😊
Dr. Banzuela

LAMINAR VS. TURBULENT BLOOD FLOW (BF) © Topnotch Medical Board Prep

• Laminar Blood flow: Streamline blood flow, with blood velocity Remember the normal values of the various blood vessels above. Observe also
fastest in the center and slowest near the vessel walls that the systolic pressure in the branches of the aorta (the one labeled “large
arteries” here), is higher than the aorta itself – again, as previously mentioned,
• Turbulent Blood Flow: irregular, disorderly blood flow
this is based dun sa pagtama ng dugo sa mga branching points ng aorta.
associated with high Reynolds Number (>2000) & bruits Dr. Banzuela
(audible vibrations)
Pressure differential
Pressure (mmHg) in… (mmHg) between
Aorta and the…
Left Right Right
Aorta Left Vent
Vent Vent Vent
Systole 120 121 25 -1 95
Diastole 80 0 0 80 80
Adapted from Table 33-4. Barrett et al. Ganong’s Review of Medical Physiology. 26th ed. 2019
Basis why blood flow to coronary arteries occur during diastole:
• Shear Stress
Contractility of the cardiac muscles occurs during systole,
o Tangential force of blood flowing on the blood vessel compressing the coronary vessels; coronary vessels have blood flow
endothelial surface during diastole only
o High shear stress: seen in laminar blood flow Dr. Banzuela

• Anemia: ↓ blood viscosity → Turbulent BF


• Atherosclerotic blood vessel → ↑ blood velocity → Turbulent BF ARTERIAL PRESSURES
DESCRIPTION ANSWER
Laminar blood flow is normal, turbulent blood flow is abnormal.
Turbulence is predicted by Reynold’s number. The higher the Reynolds Highest Arterial Blood Pressure SYSTOLIC PRESSURE
number, the greater the probability of turbulence. Reynolds number – take Lowest Arterial Blood Pressure DIASTOLIC PRESSURE
a look at its formula. Yung viscosity (n) is inversely proportional to your = Systolic Pressure – Diastolic
PULSE PRESSURE (PP)
Reynolds number. So saan ka nakakita ng turbulent blood flow – anemia Pressure
or polycythemia? Answer: anemia. Mababa ang n, mataas ang Reynolds. = Stroke Volume / Arterial
Saan ka naman makakakita ng higher resistance to blood flow, and PULSE PRESSURE
Compliance
lower blood flow – anemia or polycythemia? Answer: polycythemia. Kasi
n is directly proportional to R based on law of Poiseuille. Be careful with
Most important determinant of
STROKE VOLUME
this anemia vs. polycythemia issue. Anemia: turbulent blood flow. Pulse Pressure
Polycythemia: higher resistance to blood flow. = 2/3 (Diastole) + 1/3 (Systole) MEAN ARTERIAL
Q: Which is NOT associated with turbulence - murmur, bruit, polycythemia? = Diastole + 1/3 PP PRESSURE (MAP)
A: polycythemia (ANEMIA is the one associated with turbulence) EF = SV / EDV
Dr. Banzuela CO = HR x SV
Important Cardio Formulas
✔GUIDE QUESTION Where EF=ejection fraction;
The tendency for blood flow to be turbulent is increased by EDV is end-diastolic volume
(A) increased viscosity Normal Pulmonary Artery
15-25 / 8-10 mmHg
(B) increased hematocrit Pressure
(C) partial occlusion of a blood vessel Normal Ratio of systemic to
(D) decreased velocity of blood flow 3:1
3-15. Costanzo LS. BRS Physiology. 7 ed. 2019.
pulmonary pressure
th

Because partial occlusion of a blood vessel will decrease the cross-


CENTRAL VENOUS
sectional area, increasing blood flow velocity (remember that blood flow Synonym: Right Atrial Pressure
velocity is inversely proportional to cross-sectional area of the vessel). PRESSURE (CVP)
Dr. Banzuela Measured using Swan-Ganz
PULMONARY CAPILLARY
CAPACITANCE/ COMPLIANCE Catheter. Estimates Left Atrial
WEDGE PRESSURE (PCWP)
Pressure.
• Distensibility of blood vessel
* PP increases with age due to â arterial compliance (â capacitance)
• Inversely proportional to elastance (stiffness)
MEAN ARTERIAL PRESSURE is also called MEAN PRESSURE; the average
pressure throughout the cardiac cycle.
Take note – the formula of pulse pressure is not just systolic pressure –
diastolic pressure. Pulse pressure = stroke volume/arterial compliance.
Wag niyo kakalimutan itong alternative formula na ito. So, what happens
to pulse pressure as you grow older? As you grow older, arterial
compliance decreases (arteries become stiffer) due to arteriolosclerosis.
• Capacitance of Veins > Arteries Because arterial compliance decreases, pulse pressure INCREASES as you
o ratio of arterial compliance to venous compliance: 1:20 grow older. These are the kinds of questions that you may encounter in
your med boards – it’s a favorite din kasi in med school.
• Capacitance of Arteries decreases with age Dr. Banzuela

Remember that easy-to-forget formula: C=V/P. Formulas like this, in the “nooks • in exercise among cardiac transplant patients, cardiac output
and crannies” of this handout, has been asked before in the med boards. increases mainly due to increase in: Stroke Volume
Dr. Banzuela
• increases when Central Venous Pressure increases: Antrial
Natriuretic Peptide (ANP)

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This handout is only valid for October 2023 PLE batch. This will be rendered obsolete for the next batch since we update our handouts regularly.
✔GUIDE QUESTION
Pulse pressure is
(A) the highest pressure measured in the arteries
(B) the lowest pressure measured in the arteries
(C) measured only during diastole
(D) determined by stroke volume
(E) decreased when the capacitance of the arteries decreases
3-33. Costanzo LS. BRS Physiology. 7th ed. 2019

3.3 CARDIAC ELECTROPHYSIOLOGY


ECG
• P wave: Atrial Depolarization
• QRS Complex: Ventricular Depolarization
• T Wave: Ventricular Repolarization
• PR Interval: depends on Conduction Velocity through AV Node
o During PR Interval, cardiac AP passes through the AV Node
© Topnotch Medical Board Prep
• QT Interval: Period of Vent Depolarization + Repolarization
INCREASED (WIDENED) DECREASED (NARROW) • PR Segment: AV Node Conduction
PULSE PRESSURE PULSE PRESSURE o During PR Interval, cardiac AP passes through the AV Node
• Well-conditioned • Heart Failure (decreased • ST Segment: isoelectric; correlates with plateau of Vent AP
endurance runner pumping)
• Old age • Blood loss (decreased blood
• Aortic regurgitation volume)
• Aortic sclerosis • Aortic stenosis (reduced
• Severe iron deficiency stroke volume)
anemia (reduced blood • Cardiac tamponade
viscosity) (decreased filling time)
• Arteriosclerosis (less
compliant artery)
• Hyperthyroidism
(increased systolic pressure
Vitamin deficiency that can cause heart failure: Vitamin B1 or Thiamine
(can cause CHF or wet beriberi)

Which is not targeted in drug therapy for heart failure - preload, afterload,
relaxation, contractility? A: Relaxation
Dr. Banzuela
© Topnotch Medical Board Prep
Refer to the ECG picture while you listen to this audio recording:

ECG
https://qrs.ly/ahebihc

Dr. Banzuela

SPECIAL NOTES ON THE ECG


ECG CHANGES ANSWER
• Stimulates AV Node → ↑ Conduction Velocity → ↓ PR Interval SYMPATHETIC NS
• Can decrease AV Node Conduction → ↓ Conduction Velocity → ↑ PR Interval
• 1st degree AV Block: all atrial impulses reach the ventricles, but PR interval is long
• 2nd degree AV Block: no all impulses conducted to ventricles, ventricular rate < atrial rate. P Wave NOT
always followed by QRS
o Mobitz Type I: (+) Wenckebach phenomenon (gradual exhaustion of impulse conduction: ECG shows
gradual increase of PR interval before a block occurs) HEART BLOCK
o Mobitz Type II: sporadically occurring blocks, (-) Wenckebach phenomenon. Constant PR intervals
before block occurs
o 3rd degree (Complete) AV Block: Atrioventricular dissociation may cause fainting, syncope,
worsening exercise intolerance from cerebral ischemia
§ Systemic Diseases that can cause 3rd degree AV block: amyloidosis, sarcoidosis, SLE
• Flat/inverted T waves
• prominent U waves (increased susceptibility to Torsades de Pointes)
HYPOKALEMIA
• ↑ amplitude and width of P waves
• ST depression, QT Prolongation
• Low P waves, Tall T waves HYPERKALEMIA
• Prolonged QT Interval: associated with long QT syndrome (can cause sudden fainting and sudden
death), torsades de pointes (can cause ventricular arrhythmias/ ventricular fibrillation) HYPOCALCEMIA
o One drug that can cause torsades de pointes: macrolides
• Shortened QT Interval HYPERCALCEMIA
Q-WAVE INFARCT /
• ST Segment Elevation
TRANSMURAL INFARCT
NON-Q-WAVE INFARCT /
• ST Segment Depression
SUBENDOCARDIAL INFARCT
1st degree AV block: prolonged PR interval. It is the AV block that does NOT require treatment
2nd degree: dropped QRS complex. 3rd degree: atrioventricular dissociation (meaning may sariling rhythms na ang atrium vs. ventricles).
3rd degree is the one associated with SYNCOPE. Analogy: Parang stages sa break-up yan. 1st degree AV block – para kayong bf-gf na nagkakalaboan na; nagiging
malayo na feelings nyo sa isa’t isa (prolonged PR interval). 2nd degree: you drop dates and meetings na for one another (dropped QRS complex). 3rd degree:
hiwalayan na talaga – you have separate lives na (AV dissociation).
Dr. Banzuela

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This handout is only valid for October 2023 PLE batch. This will be rendered obsolete for the next batch since we update our handouts regularly.
Listen to the audio recording while you study and highlight the table on the
✔GUIDE QUESTIONS
autonomic effects on HR and SV below:
The ventricles are completely depolarized during which isoelectric
portion of the electrocardiogram (ECG)?
(A) PR interval (D) ST segment AUTONOMIC EFFECTS
(B) QRS complex (E) T wave ON HR AND SV
3-17. Costanzo LS. BRS Physiology. 7 ed. 2019
(C) QT interval th
https://qrs.ly/qfebihk
A person’s electrocardiogram (ECG) has no P wave, but has a normal QRS
complex and a normal T wave. Therefore, his pacemaker is located in the Dr. Banzuela
(A) sinoatrial (SA) node (D) Purkinje system AUTONOMIC EFFECTS ON HR AND CV
(B) atrioventricular (AV) node (E) ventricular muscle
3-4. Costanzo LS. BRS Physiology. 7 ed. 2019 DESCRIPTION ANSWER
(C) bundle of His th

A 30-year-old female patient’s electrocardiogram (ECG) shows two P Produces changes in


INOTROPIC EFFECT
waves preceding each QRS complex. The interpretation of this pattern is Contractility
(A) decreased firing rate of the pacemaker in the sinoatrial (SA) node Produces changes in
LUSITROPIC EFFECT
(B) decreased firing rate of the pacemaker in the atrioventricular (AV) node Rate of Relaxation
(C) increased firing rate of the pacemaker in the SA node Produces changes in
(D) decreased conduction through the AV node CHRONOTROPIC EFFECT
Heart Rate
(E) increased conduction through the His-Purkinje system
Produces changes in
Kindly review the videos on the cardiac AP and SA Node AP found in Cell DROMOTROPIC EFFECT
Conduction Velocity
Physiology Module VENTRICULAR CONTRACTION
Dr. Banzuela Inotropes affect:
CARDIAC ACTION POTENTIAL (STROKE VOLUME)
• Stable RMP: -90mV (almost similar to K equilibrium potential) Chronotropes affect: SA NODE (HEART RATE)
• Cardiac AP: Phase 0,1,2,3,4 AV NODE
Dromotropes affect:
(CONDUCTION VELOCITY)
CARDIAC PACEMAKERS Dromotropes are
• Sequence: Sino-Atrial (SA) node à Atriventricular (AV) Node INWARD CALCIUM CURRENT
affected by:
à Bundle of His à Purkinje Fibers STRONGER (positive inotrope),
• SA Node: Master Pacemaker (exerts overdrive suppression of Beta-1 stimulation of BRIEFER (positive lusitrope) &
other pacemakers) the heart would cause: MORE FREQUENT (positive
• AV Node, Bundle of His, Purkinje: Latent Pacemakers chronotrope) CONTRACTIONS
• When latent pacemakers assume pacemaking activity: Ectopic Caffeine is an example of a positive chronotropic agent. It acts by
Pacemaker inhibiting phosphodiesterase (PDE), causing inhibition of the
• Intrinsic rate of Phase 4 Depolarization (and Heart Rate): degradation of cAMP to 5' AMP
SA Node > AV Node > His-Purkinje Dr. Banzuela

o SA Node: 70-80 beats/min ✔GUIDE QUESTION


o AV Node: 40-60 beats/min (slowest conduction velocity in the Myocardial contractility is best correlated with the intracellular
conduction pathway at 0.01-0.05 m/sec) concentration of
o Bundle of His: 40 beats/min (A) Na+ (D) Cl−
o Purkinje Fibers: 15-20 beats/min (fastest conduction velocity (B) K+ (E) Mg2+
3-37. Costanzo LS. BRS Physiology. 7 ed. 2019
(C) Ca2+ th

in the conduction pathway at 2-4 m/sec)


Remember – Calcium is to Muscle what Spinach is to Popeye.
SA Node has the shortest duration among the pacemakers – this is the Dr. Banzuela
reason why it’s the master pacemaker (nag-aattempt pa lang mag self-
excite yung ibang pacemakers, na-stimulate na sila ng prior pacemakers FACTORS THAT CAUSES POSITIVE INOTROPISM
like the SA Node). • Increased Heart Rate
So, what will happen when the SA Node dies (e.g., due to MI)? Answer: HR o The greater the number of AP, the greater the intracellular Ca2+
will decrease, since the duration of the action potential of the other released from SR, the greater the cardiac contractility, e.g.
pacemakers are longer, leading to less cycles per minute, leading to § Positive Staircase / Bowditch Staircase / Treppe
decrease in heart rate. - the faster the heart beats, the stronger the heart beats
Dr. Banzuela
§ Postextrasystolic Potentiation (in Premature Ventricular
SA NODE AP
Contraction (PVC) or Extrasystole)
• Has unstable RMP (Phase 4)
- The next normal beat immediately after PVC will have
• No sustained Plateau, no Phase 1, no Phase 2 greater force of contraction due to greater Ca influx due to
• Contains Phase 4, 0, 3 <see discussion on cardiac muscles> increased ventricular filling time
• If channels or “slow, funny sodium channels”: responsible for - predisposes athletes to PVCs: Bradycardia
slow Na influx during Phase 4
- may compromise stroke volume post-M.I.: increased heart
o Triggered by K+ efflux of Phase 3 which causes automaticity
rate (due to decreased filling time)
and pacemaking activity of the SA Node (Phase 3 will always
• Sympathetic NS stimulation
cause Phase 4)
o Increases Ca2+ influx in Phase 2 of Cardiac AP
o Increases SR Ca2+-ATPase pump (through phosphorylation of
CONDUCTION VELOCITY
phospholamban) → more Ca2+ accumulated by SR → more Ca2+
• Time required for excitation to spread throughout the cardiac available for release to the sarcomere
muscle § increased by increasing phospholamban: concentration of
• Depends on size of the inward current during the upstroke of Ca2+ within the SR
the cardiac AP
• Cardiac Glycosides (digitalis)
• Fastest: Purkinje fibers o Inhibition of some cardiac Na-K-ATPase pump → ↓ activity of
• Slowest: AV node (allows time for ventricular filling) Na+-Ca2+ pump → ↑ intracellular Ca2+
✔GUIDE QUESTION o Drug that does NOT decrease cardiac contractility: Digitalis
The physiologic function of the relatively slow conduction through the There are 3 factors that increases stroke volume (positive inotropes):
atrioventricular (AV) node is to allow sufficient time for digitalis, beta-1 stimulation and INCREASED HEART RATE. The faster the
(A) runoff of blood from the aorta to the arteries heart beats, the stronger the heart beats → this is the staircase effect and
(B) venous return to the atria has something to do with increased amount of calcium being released from
(C) filling of the ventricles the sarcoplasmic reticulum with each round of heart contraction. PVC
(D) contraction of the ventricles (Extrasystole) is a form of arrhythmia where the heart prematurely
(E) repolarization of the ventricles 3-41. Costanzo LS. BRS Physiology. 7 ed. 2019
th
contracts. During PVC, stroke volume decreases. But during the first
Between the atria and ventricles is an area of fibrous tissue with little normal contraction after PVC, stroke volume will actually increase (due to
gap junctions. This causes the AV nodal delay (pinakamabagal ang increased ventricular filling time caused by shifting from abnormal rhythm
conduction velocity sa AV Node). Importante yang AV nodal delay na to normal rhythm). This increase in SV during the first normal contraction
yan – it ensures that the atrium will contract first before the ventricles, after PCV is called POSTEXTRASYSTOLIC POTENTIATION. Staircase effect
and it allows for ventricular filling. and Postextrasystolic potentiation are the mechanisms for increased
Dr. Banzuela heart rate causing an increase in stroke volume.
Dr. Banzuela

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TOPNOTCH MEDICAL BOARD PREP PHYSIOLOGY MAIN HANDOUT BY DR. ENRICO PAOLO C. BANZUELA
For inquiries visit www.topnotchboardprep.com.ph or https://www.facebook.com/topnotchmedicalboardprep/
This handout is only valid for October 2023 PLE batch. This will be rendered obsolete for the next batch since we update our handouts regularly.
✔GUIDE QUESTIONS • Cardiac Afterload:
Which of the following agents or changes has a negative inotropic effect o Equivalent to Aortic Pressure for the Left ventricle, and
on the heart? Pulmonary Artery Pressure for the Right ventricle
(A) Increased heart rate (D) Acetylcholine (ACh) § Inversely proportional to velocity of contraction at fixed
(B) Sympathetic stimulation (E) Cardiac glycosides
3-55. Costanzo LS. BRS Physiology. 7 ed. 2019 muscle length
(C) Norepinephrine th

§ ↑ Afterload → ↓ Cardiac Output (by increasing resistance to


ACh kasi is the final neurotransmitter for the PARASYMPATHETIC ventricular outflow)
nervous system. And while para does not have a direct negative
• Frank-Starling Mechanism
inotropic effect on the heart (remember para has no direct effect on the
cardiac ventricles), para can affect heart rate – it decreases your heart o ↑ Venous Return (VR) → ↑ R Atrial Pressure → ↑ EDV (Preload)
rate. Decreased heart rate will cause a negative inotropic effect. So, ACh → ↑ Stretch of cardiac sarcomeres (↑ ventricular fiber length) →
has an indirect negative inotropic effect. greater force of contraction (due to greater tension) → ↑ SV →
Dr. Banzuela ↑CO
An electrocardiogram (ECG) on a person shows ventricular • Bainbridge Reflex
extrasystoles. The extrasystolic beat would produce
(A) increased pulse pressure because contractility is increased
o ↑ Venous Return (VR) → ↑ R Atrial Pressure → stimulates
(B) increased pulse pressure because heart rate is increased cardiopulmonary baroreceptors (low-pressure receptors) →
(C) decreased pulse pressure because ventricular filling time is increased ↑HR → ↑CO
(D) decreased pulse pressure because stroke volume is decreased Increased contractility in the Frank-Starling diagram is demonstrated by
(E) decreased pulse pressure because the PR interval is increased increased Cardiac output for a given EDV
3-6. Costanzo LS. BRS Physiology. 7th ed. 2019
Not affected by stroke volume - pulse pressure, preload, afterload,
Remember the formula for Pulse Pressure is not just systolic pressure –
contractility? A: Afterload (determined mainly by aortic/pulmonary
diastolic pressure. The other formula is SV/arterial compliance. During
artery pressure)
extrasystolic beat (PVC), SV decreases due to premature contraction Dr. Banzuela
that lead to decreased ventricular filling time. Decreased SV means
decreased pulse pressure (PP = SV/arterial compliance again). FRANK-STARLING MECHANISM VS.
MNEMONICS
Dr. Banzuela BAINBRIDGE REFLEX
An electrocardiogram (ECG) on a person shows ventricular extrasystoles.
Frank-Starling Mechanism Bainbridge Reflex
After an extrasystole, the next “normal” ventricular contraction produces
(A) increased pulse pressure because the contractility of the ventricle
↑ VR → ↑ SV → ↑ CO ↑ VR → ↑ HR → ↑ CO
is increased IMPORTANT CARDIO CONCEPTS
(B) increased pulse pressure because total peripheral resistance (TPR) is • Stroke Volume
decreased
(C) increased pulse pressure because compliance of the veins is
o Blood ejected by the ventricle per heart beat
decreased o Equal to EDV - ESV
(D) decreased pulse pressure because the contractility of the ventricle is o Normal Value: 70mL
increased • Ejection Fraction
(E) decreased pulse pressure because TPR is decreased o Percentage of EDV that is actually ejected by the ventricle
3-7. Costanzo LS. BRS Physiology. 7th ed. 2019
After PVC, there is increased ventricular filling time, increasing SV. This
o Equal to SV/EDV
will increase Pulse pressure (PP = SV/arterial compliance once again) o Normal value: 55%
Dr. Banzuela • Cardiac Output
An increase in contractility is demonstrated on a Frank–Starling diagram: o Total blood volume ejected per unit of time
(A) by increased cardiac output for a given end-diastolic volume o Equal to HR x SV
(B) by increased cardiac output for a given end-systolic volume
o Normal value: 5L/min (resting)
(C) by decreased cardiac output for a given end-diastolic volume
Here is an example of how they ask the “nooks and crannies” in Physiology.
(D) by decreased cardiac output for a given end-systolic volume
If they ask, “If a 70kg healthy male has a heart rate of 100 beats/min, what
is the Cardiac Output?”
AUTONOMIC EFFECTS ON HEART AND BLOOD VESSELS Most students know the formula for Cardiac Output (CO=HR x SV). But they
• Sympathetic NS see this as an impossible question since only the heart rate was given and
o HR, Conduction Velocity (AV Node) and Cardiac Contractility: ↑ not the stroke volume. Knowing the “nooks and crannies” means you can
via β1 deduce that a 70kg male is the classic “average person” used in physio
o Skin and splanchnic arterioles, veins: vasoconstrict via 𝛼1 examples. He would have the classic stroke volume of 70mL. That value -
o Skeletal muscle arterioles: vasodilate via 𝜷2 70mL - is listed in this handout
So to answer the question: CO = HR x SV = (100 beats/min) x (70mL/beat)
o Ephedrine effects: tachycardia, palpitations, arteriolar = 7000mL/min.
smooth muscle contraction leading to vasoconstriction This physio main handout is a compilation of multiple books guided by
• Parasympathetic NS continuous student feedback. Do not merely memorize it. Understand, and
o HR, Conduction Velocity (AV Node) and Atrial Contractility: be aware of the nooks and crannies. Questions in the med boards will
↓ via M2 require analysis and integration of the material.
Dr. Banzuela
o Little to no effect on blood vessels
FICK EQUATION
✔GUIDE QUESTION • Alternative way of computing for cardiac output
Which receptor mediates constriction of arteriolar smooth muscle?
(A) α1 Receptors (C) β2 Receptors
(B) β1 Receptors (D) Muscarinic receptors • CO = Cardiac Output
Remember our discussion in the Neuro module. Alpha-1 causes smooth • VO2 = steady state Oxygen Consumption by the body
muscle contraction. Beta-2 causes smooth muscle relaxation. Alpha-1 • AVO2 = difference in arterial O2 content and mixed venous O2
causes vasoconstriction. Beta-2 causes vasodilation. content
Dr. Banzuela
Remember the formulas above. SV = EDV-ESV. EF = SV/EDV. Do NOT
confuse the formula for EF with Pulse Pressure (PP). PP = SV/arterial
3.4 CARDIAC OUTPUT compliance. Finally, please remember that there is an alternative formula
Listen to this audio guide while reading the section below on preload, for computing for CO → the Fick Equation. Wag kalimutan yang Fick
afterload, FSM and BR: Equation na yan. Paborito yan across multiple batches.
Dr. Banzuela

✔GUIDE QUESTIONS
PRELOAD, AFTERLOAD, A hospitalized patient has an ejection fraction of 0.4, a heart rate of 95
FSM AND BR beats/min, and a cardiac output of 3.5 L/min. What is the patient’s end-
https://qrs.ly/wvebijj diastolic volume?
(A) 14 mL (D) 92 mL
Dr. Banzuela (B) 37 mL (E) 140 mL
3-59. Costanzo LS. BRS Physiology. 7 ed. 2019
(C) 55 mL th

LENGTH-TENSION RELATION IN THE VENTRICLES EF = SV/EDV


• Cardiac Preload: EDV = SV/EF
o Equivalent to End-Diastolic Volume (EDV), which in turn is CO = HR x SV
influenced by Right Atrial Pressure SV = CO/HR = 3500/95 = 36.8mL
§ ↑ Preload → ↑ Cardiac Output (by increasing SV) EDV = 36.8/0.4 = 92mL
Dr. Banzuela

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TOPNOTCH MEDICAL BOARD PREP PHYSIOLOGY MAIN HANDOUT BY DR. ENRICO PAOLO C. BANZUELA
For inquiries visit www.topnotchboardprep.com.ph or https://www.facebook.com/topnotchmedicalboardprep/
This handout is only valid for October 2023 PLE batch. This will be rendered obsolete for the next batch since we update our handouts regularly.
✔GUIDE QUESTIONS ✔GUIDE QUESTIONS
The following measurements were obtained in a male patient: EF = SV/EDV. An increase in SV will cause an increase in EF. When SV
Central venous pressure: 10 mm Hg increases, there will be less blood in the ventricles after contraction →
Heart rate: 70 beats/min decreased ESV. That’s why B is the answer here.
Pulmonary vein [O2] = 0.24 mL O2/mL Dr. Banzuela

Pulmonary artery [O2] = 0.16 mL O2/mL


• Stroke work
Whole body O2 consumption: 500 mL/min
What is this patient’s cardiac output?
o Work heart performs on each beat
(A) 1.65 L/min (D) 6.25 L/min o Main Energy for Stroke Work: Fatty Acids
(B) 4.55 L/min (E) 8.00 L/min • Cardiac O2 consumption
(C) 5.00 L/min 3-28. Costanzo LS. BRS Physiology. 7 th ed. 2019
o Directly related to amount of tension developed by ventricles
o Increased by an increase in the following: afterload, size of the
heart, contractility, heart rate
✔GUIDE QUESTION
Fick Equation – don’t forget it. =) Which of the following changes will cause an increase in myocardial O2
Dr. Banzuela
consumption?
If the ejection fraction increases, there will be a decrease in
(A) Decreased aortic pressure
(A) cardiac output (D) pulse pressure
(B) Decreased heart rate
(B) end-systolic volume (E) stroke volume
3-5. Costanzo LS. BRS Physiology. 7 ed. 2019 (C) Decreased contractility
(C) heart rate th

(D) Increased size of the heart


(E) Increased influx of Na+ during the upstroke of the action potential
3-46. Costanzo LS. BRS Physiology. 7th ed. 2019

3.5 CARDIAC CYCLE

Watch these 2 videos on the cardiac


cycle while reading the corresponding
portions of the handout below:

CARDIAC CYCLE PART 1/2


https://qrs.ly/yvebio2

CARDIAC CYCLE PART 2/2


https://qrs.ly/ywebiot
Dr. Banzuela

• Cardiac events that occur in a


single heartbeat illustrated in the
Wigger Diagram
• Wigger Diagram has the following
components:
o Heart Sounds
(Phonocardiogram)
o ECG
o Ventricular Volume Curve
o Ventricular Pressure Curve
o Atrial Pressure Curve
o Aortic Pressure Curve

© Topnotch Medical Board Prep

7 PHASES OF THE CARDIAC CYCLE • Heart Sounds: 4th heart sound maybe heard due to atria
1. Atrial Contraction/ Systole (occurs during distal third of contracting against stiff ventricles (e.g. in LV hypertrophy)
diastole) • Atrial Fibrillation is most likely accompanied by increase in: Left
2. Isovolumic Contraction Atrial Pressure. Ventricular fibrillation in comparison leads to
3. Rapid Ventricular Ejection fatal arrhythmia
4. Slow/Reduced Ventricular Ejection 2. ISOVOLUMIC CONTRACTION
5. Isovolumic Relaxation • ECG: preceded by QRS complex
6. Rapid Ventricular Filling (occurs during early third of • Atrial Pressure Curve: c wave is seen
diastole) • Ventricular Pressure: Increases but Ventricular Pressure is still
7. Slow/Reduced Ventricular Filling (occurs during middle < Aortic Pressure
third of diastole) o Semilunar valves are still closed
1. ATRIAL CONTRACTION § Blood will NOT flow from LV to Aorta
• Occurs during the distal third of diastole • Ventricular Volume: remains the same
• NOT essential for ventricular filling • Ventricular Pressure > Atrial Pressure
• ECG: preceded by p-wave o AV valves will close
• Atrial Pressure: Increases slightly • Heart Sounds: S1 will be heard
• Ventricular Pressure: Increases slightly Remember: if Aortic Pressure > Ventricular Pressure, there is no ventricular
• Ventricular Volume: Increases slightly ejection (no outflow of blood from the ventricle. Ventricular Pressure >
Aortic Pressure if you want ejection of blood from the ventricles.
• Atrial Pressure curve: a-wave seen Dr. Banzuela

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3. RAPID VENTRICULAR EJECTION • Ventricular Volume: remains the same
• Atrial filling begins • Ventricular Pressure < Aortic Pressure
• Ventricular Pressure: rapidly increases to a point that it is now o Semilunar valves will close
greater than Aortic Pressure • Heart Sounds: S2 is heard (physiologic split S2: occurs during
o Semilunar valves open inspiration)
§ Blood will flow from LV to aorta • Aortic Pressure Curve: Incisura / Dicrotic Notch seen
• Ventricular Volume: rapidly decreases o Dicrotic notch: closure of aortic valve cause vibrations in the
• during ventricular ejection, pressure difference is smallest in aorta near the aortic valve causing a slight and transient
magnitude between: Left Ventricle and Aorta increase in aortic pressure
Take note: the Wigger diagram in BRS Physio utilizes “venous pulse pressure” 6. RAPID VENTRICULAR FILLING
curve instead of “atrial pressure” curve (the one utilized in the Wigger • Ventricular Pressure: rapidly decreases to a point that it is now
diagram of Guyton and the textbook). Kaya magkaiba placing ng c wave nila.
less than Atrial Pressure
In the exam, if venous pulse pressure cure ang tinanong, use rapid ventricular
ejection, if atrial pressure curve, use isovolumic contraction. o Opening of the Atrioventricular valves
Dr. Banzuela § Blood rapidly flows from Atrium to Ventricles
4. REDUCED VENTRICULAR EJECTION • Heart Sounds: 3rd Heart sound may be heard (due to rapid
• ECG: T-wave occurs ventricular filling)
• Ventricular Pressure: Decreases • Ventricular Volume: rapidly increases
• Ventricular Volume: Decreases 7. REDUCED VENTRICULAR FILLING (DIASTASIS)
• Aortic pressure: decreases because of runoff of blood from large
• Longest phase of the cardiac cycle
arteries to smaller arteries
o Dependent on heart rate
5. ISOVOLUMIC RELAXATION • Ventricular Volume: Reduced increase
• ECG: preceded by t-wave MNEMONICS CARDIAC CYCLE
o aortic valve closes during this portion of the ECG: T-wave 3 Instances when Atrial Pressure Increases
o Atrial Pressure Curve: v wave seen a wave: atrial contraction
• Ventricular Pressure: rapidly decreases but Ventricular c wave: contraction of ventricles, carotid pulsation; closed TV
Pressure > Atrial Pressure bulging into right atrium
o AV valves are still closed v wave: venous blood going to atria
o No blood flow from Atria to Ventricles
Vp Vv
DIASTOLE
late (3/3)

1. Atrial P wave a
S4 Non-compliant ventricular ↑ ↑
Contraction (atrial depolarization) wave

2. Isovolumic Closure of Atrioventricular VP < AoP QRS complex (ventricular c


S1 ↑↑ Ø
Contraction ((AV) valves VP > AP depolarization) wave
3. Rapid VP > AoP
SYSTOLE

Ventricular Opening of SL ↑ ↓↓
Ejection valves
4. Slow Ventricular T wave
↓ ↓
Ejection (ventricular repolarization)
5. Isovolumic Closure of Semilunar (SL) VP < AoP v INCISURA
S2 ↓↓ Ø
Relaxation valves VP > AP wave (dicrotic notch)
DIASTOL

VP < AP
E early
(1/3)

6. Rapid
S3 Rapid ventricular filling Opening of ↑ ↑↑
Ventricular Filling
AV valves
DIASTOLE
mid (2/3)

7. Slow Ventricular
Ø ↑
Filling

NOTES: VP = Ventricular pressure; VV = Ventricular volume; AP = Atrial pressure; AoP = Aortic pressure; ECG = electrical → mechanical
Contributed by Jake Bryan Cortez, MD

✔GUIDE QUESTIONS HEART SOUNDS


During which phase of the cardiac cycle does the mitral valve open? HEART
CAUSE PHASE
(A) Atrial systole SOUND
(B) Isovolumetric ventricular contraction Isovolumic
(C) Rapid ventricular ejection S1 Closure of AV Valves
Contraction
(D) Reduced ventricular ejection
S2
(E) Isovolumetric ventricular relaxation 3-58. Costanzo LS. BRS Physiology. 7 ed. 2019 th Isovolumic
(split during Closure of Semilunar Valves
The correct answer is actually at the END of isovolumic ventricular Relaxation
inspiration)
relaxation (or the start of rapid ventricular filling)
Dr. Banzuela Rapid Ventricular Filling (Normal
During which phase of the cardiac cycle is aortic pressure highest? in children, young adults,
(A) Atrial systole pregnant patients; seen in Left- Rapid
(B) Isovolumetric ventricular contraction S3 Sided S3 in patients with Ventricular
(C) Rapid ventricular ejection congestive heart failure (CHF) Filling
(D) Reduced ventricular ejection indicative of cardiovascular
(E) Isovolumetric ventricular relaxation 3-36. Costanzo LS. BRS Physiology. 7 ed. 2019 th
morbidity, mortality)
The correct answer is actually BETWEEN rapid ventricular ejection and Atrial
reduced ventricular ejection. Stiff Ventricles / Vibration in the
S4 Contraction/
Dr. Banzuela ventricular wall during systole
During which phase of the cardiac cycle is ventricular volume lowest? Systole
(A) Atrial systole
(B) Isovolumetric ventricular contraction
(C) Rapid ventricular ejection
(D) Reduced ventricular ejection
(E) Isovolumetric ventricular relaxation
3-45. Costanzo LS. BRS Physiology. 7th ed. 2019

Two valves that open during systole: aortic valve and pulmonic valve.
Dr. Banzuela
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PHYSIOLOGICALLY SPLIT S2 CASE DESCRIPTION VALVULAR LESION
67/M with RHD presents with difficulty
MITRAL
breathing while exercising. (+)
REGURGITATION
holosystolic murmur at the L 5th ICS MCL.
(MR)
Murmur loudest at the apex, radiates to
(WITH INCREASED V
axilla, enhanced during expiration, and
WAVE)
when patient is instructed to make a fist:
75/F with exertional dyspnea, and
episode of syncope while dancing with her AORTIC STENOSIS
husband. (+) prominent systolic ejection (AS)
click and crescendo-decrescendo murmur (WITH DECREASED
over the R sternal border that radiates to PULSE PRESSURE)
the carotid arteries:
The table above contains classic descriptions for valvular lesions. Understand
and remember them. Pinakaimportante yung sa aortic regurgitation /
© Topnotch Medical Board Prep insufficiency. If you see murmur with “wide pulse pressure” (or a BP reading
na sobrang taas ng systolic pressure and sobrang baba ng diastolic pressure,
• Common ECG finding in Paradoxical Splitting of the 2nd heart e.g., BP=150/20), think Aortic Regurgitation.
sound (P2 comes before A2): Left Bundle Branch Block
Also, child with cardiac valvular defect characterized as head nodding in
• Conditions associated with exaggeration of normal splitting synchrony with heart beat: think Aortic Insufficiency (de Musset Sign)
(Wide Split S2): Right Bundle Branch Block, Pulmonary Dr. Banzuela
Stenosis, Mitral Valve Regurgitation, VSD
• Auscultatory hallmark of Atrial Septal Defect (ASD): FIXED 3.6 REGULATION OF BLOOD PRESSURE
SPLITTING BP CONTROL
Whenever you inhale, there is a decrease in intrathoracic pressure. This • Vasomotor Area of the Medulla
decreased intrathoracic pressure has an effect not just on the lungs but also o Center responsible for regulation of HR and BP
on the blood vessels going to the left and right atrium. It increases the o Found in the Medulla
venous return of the Right, decreases the venous return on the Left. § Lateral Portion: Excitatory Area (↑ HR & BP)
Increased blood in the R atrium and consequently R ventricle will delay § Medial Portion: Inhibitory Area (↓ HR & BP)
closure of pulmonic valve. Decreased blood in the L atrium and o Controlled by the Hypothalamus and other higher nervous centers
consequently the L ventricle will result in earlier closure of the aortic valve. • Acute Control
The earlier closure of the aortic valve coupled with the delayed closure of
the pulmonic valve will result in the splitting of the second heart sound
o ANS Control, Baroreceptors, Chemoreceptors, Low-Pressure
(remember – the second heart sound is caused by the closure of the Receptors, CNS Ischemic Response
semilunar valves – the aortic and pulmonic valves). • Long-term Control
Dr. Banzuela o Renin-Angiotensin-Aldosterone-System (RAAS)
✔GUIDE QUESTION • ANS
Inspiration “splits” the second heart sound because o Sympathetic > Parasympathetic
(A) the aortic valve closes before the pulmonic valve o To increase BP via ANS:
(B) the pulmonic valve closes before the aortic valve § Arteriolar Vasoconstriction → ↑ TPR → ↑ BP
(C) the mitral valve closes before the tricuspid valve § Venous Vasoconstriction → ↑ VR → ↑ CO → ↑BP
(D) the tricuspid valve closes before the mitral valve
§ ↑ HR & SV via 𝜷1 Receptors of the Heart → ↑ CO → ↑ BP
(E) filling of the ventricles has fast and slow components
3-23. Costanzo LS. BRS Physiology. 7th ed. 2019 Medulla contains the vasomotor center. This is the center that controls BP
and HR. if you shoot someone between the eyes and it destroys the medulla,
MURMURS AND LOCATIONS the person will surely die because of the destruction of the vasomotor
center – wala nang BP at HR yan.
MURMUR LOCATION BEST HEARD Dr. Banzuela
Aortic Valve 2nd intercostal (ICS) Right ANS EFFECT ON THE HEART AND BLOOD VESSELS
Parasternal SYMPATHETIC PARASYMPATHETIC
Pulmonary Valve 2nd ICS Left Parasternal Effect Receptor Effect Receptor
Tricuspid Valve 4th-5th ICS Left Parasternal Heart Rate ↑ 𝛽1 ↓ M2
Mitral Valve 5th ICS Left MCL Conduction
Velocity (AV ↑ 𝛽1 ↓ M2
Node)
↓ (atria
Contractility ↑ 𝛽1 M2
only)
VASCULAR SMOOTH MUSCLE
Skin, Dilation
Constriction 𝛼1 M3
splanchnic (EDRF)
Skeletal Dilation
Constriction 𝛼1 M3
Muscle (EDRF)
Dilation 𝛽2 - -
Veins Constriction 𝛼1 - -

✔GUIDE QUESTIONS
Which receptor mediates slowing of the heart?
(A) α1 Receptors (C) β2 Receptors
© Topnotch Medical Board Prep (B) β1 Receptors (D) Muscarinic receptors
Regarding the location of heart murmurs – we have a classic mnemonic for 3-54. Costanzo LS. BRS Physiology. 7th ed. 2019

this when we were first year medical students: “Always Pray To Mary” Which muscarinic receptor? M1, M2 or M3? Answer: M2. Ginawa nyo yung
(with your hand going in a “z” direction. See pic above). Eventually my mnemonic natin in your head sa neuro module, right? J
classmates changed this to “Ayos Pare, Tagay Muna” =) Dr. Banzuela
Dr. Banzuela Propranolol has which of the following effects?
VALVULAR LESIONS (A) Decreases heart rate
CASE DESCRIPTION VALVULAR LESION (B) Increases left ventricular ejection fraction
66/M has diastolic murmur over L sternal AORTIC (C) Increases stroke volume
border, decreased diastolic pressure, REGURGITATION (D) Decreases splanchnic vascular resistance
increased pulse pressure: (AR) (E) Decreases cutaneous vascular resistance
3-53. Costanzo LS. BRS Physiology. 7th ed. 2019
41/M IV drug user has early systolic When propranolol is administered, blockade of which receptor is
TRICUSPID
murmur. Distance between the height of responsible for the decrease in cardiac output that occurs?
REGURGITATION
the blood in the R IJV and sternal angle is (A) α1 Receptors (D) Muscarinic receptors
(TR)
7cm (normal is 3cm): (B) β1 Receptors (E) Nicotinic receptors
3-44. Costanzo LS. BRS Physiology. 7 ed. 2019
(C) β2 Receptors th

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Listen to this audio recording while reading about the Baroreceptor Reflex § ↑ Atrial Natriuretic Peptide (ANP): ↑ Na+ & H2O excretion
part: - in dehydration, there is ↑ ADH, ↑ Angiotensin II,
↑Aldosterone, ↑ NE and ↓ ANP
- ANP is released in response to increased atrial pressure
BARORECEPTOR REFLEX from increased blood volume
https://qrs.ly/cmebip4 § ↓ Anti-Diuretic Hormone (ADH): ↑ urine output
§ Renal Vasodilation: ↑ urine output
Dr. Banzuela § ↑ Heart Rate (Bainbridge Reflex): helps match VR w/ CO
✔GUIDE QUESTIONS • CNS Ischemic Response
Following a sympathectomy, a 66-year-old man experiences orthostatic o The vasomotor center itself responds directly to the ischemia
hypotension. The explanation for this occurrence is during low BP
(A) an exaggerated response of the renin–angiotensin–aldosterone o Starts at BP<60mmHg and optimal at a BP=15-20mmHg
system o The “last-ditch” stand:
(B) a suppressed response of the renin–angiotensin–aldosterone § All systemic arterioles vasoconstrict severely EXCEPT for
system Coronary Vessels, Cerebral Vessels
(C) an exaggerated response of the baroreceptor mechanism
• Cushing Reaction or Cushing Reflex
(D) a suppressed response of the baroreceptor mechanism
3-16. Costanzo LS. BRS Physiology. 7th ed. 2019 o Occurs in response to increased Intracranial Pressure (e.g.,
An acute decrease in arterial blood pressure elicits which of the following following head trauma)
compensatory changes? o Triad: hypertension (HPN), Bradycardia, Irregular Respirations
(A) Decreased firing rate of the carotid sinus nerve o Occurs in response to increase in intracranial pressure: BP
(B) Increased parasympathetic outflow to the heart increases while heart rate decreases (Cushing Reaction)
(C) Decreased heart rate
(D) Decreased contractility
• Long-term Control
(E) Decreased mean systemic pressure 3-21. Costanzo LS. BRS Physiology. 7 ed. 2019 th
o Renin-Angiotensin-Aldosterone-System (R-A-A-S)
o Slow: Takes 20 minutes to take effect; takes several hours for
BP CONTROL optimal effects
• Baroreceptors (BR) o Activated when faster mechanisms (e.g., baroreceptors) fail to
o Act fast; Buffers minute-to-minute changes in BP regulate BP
o Stretch Receptors on the Carotid Sinus and Aortic Arch o Also responsible for maintaining normal BP despite wide
§ ↑ BP → ↑ Stretch → ↑ Firing of CN IX to Nucleus Tractus variation in salt intake
Solitarius → trigger parasympathetic response
Listen to the audio recording on RAAS as you read the next section:
§ ↓ BP → ↓ Stretch → ↓ Firing of CN IX to Nucleus Tractus
Solitarius → trigger sympathetic response
o Hering nerve: branch of CN IX that carries signals from carotid RAAS
sinus to NTS https://qrs.ly/rzebiqk
o Carotid Baroreceptors: respond increase / decrease in pressures
from 50mmHg-180 mmHg
o Aortic Baroreceptors: respond to increase in pressure >80mmHg Dr. Banzuela

o Set Point for MAP in Vasomotor Center: 100mmHg


o Post-op patient suddenly stands up after being supine. This will
increase heart rate

RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM (RAAS)


• Activated first before RAAS: Baroreceptor Reflex
• Senses decrease in NaCl delivery in the DCT: Macula Densa
• Macula Densa: stimulates Juxtaglomerular (JG) Cells (also called
Granular Cells) to release Renin
o also increases renin secretion: sympathetic nerve activity (via
𝛽1 receptors)
• Renin → converts Liver Angiotensinogen to Angiotensin I
• Lung ACE: converts Angiotensin I to Angiotensin II
• Angiotensin II Effects:
o Maintains (PRESERVES) normal GFR (vasoconstricts Efferent >
Afferent)
o Vasoconstricts systemic arterioles → ↑TPR
o Stimulates Aldosterone secretion by zona glomerulosa of the
© Topnotch Medical Board Prep adrenal cortex
• Valsalva Maneuver o ↑ Na+-H+ exchange in the PCT → contraction alkalosis
o Expiring against closed Glottis → ↑ Intrathoracic Pressure → o ↑ thirst and ADH secretion → ↑ intravascular volume
↓VR → ↓ CO and BP → sensed by BR → ↑HR o ↑ Epi, NE, Cortisol secretion → vasoconstricts arterioles
o Once you stop Valsalva Maneuver → sudden rebound ↑ in VR, • Aldosterone Effects on the KIDNEYS:
CO and BP → sensed by BR → âHR o Na+ reabsorption
• Chemoreceptors o K+ secretion
o could also induce changes in BP o H+ secretion
o Responds to low O2, high CO2 concentration whenever
✔GUIDE QUESTIONS
BP<80mmHg
Which agent is released or secreted after a hemorrhage and causes an
§ when chemoreceptors are stimulated, they activate vasomotor increase in renal Na reabsorption?
centers for systemic vasoconstriction → ↑ TPR → ↑BP (A) Aldosterone (D) Antidiuretic hormone (ADH)
• Low-pressure Receptors (Cardiopulmonary Baroreceptors) (B) Angiotensin I (E) Atrial natriuretic peptide
o In the atria and pulmonary arteries (C) Angiotensinogen 3-57. Costanzo LS. BRS Physiology. 7 ed. 2019
th

o Detects “fullness” of vascular system (↑ intravascular volume)


o In response to increased intravascular volume:
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✔GUIDE QUESTIONS STARLING FORCES
A 60-year-old businessman is evaluated by his physician, who STARLING NORMAL
determines that his blood pressure is significantly elevated at 185/130 DESCRIPTION
FORCES VALUE
mm Hg. Laboratory tests reveal an increase in plasma renin activity,
Capillary • Favors filtration;
plasma aldosterone level, and left renal vein renin level. His right renal
vein renin level is decreased. What is the most likely cause of the patient’s
Hydrostatic • determined by pressure & 25mmHg
hypertension? Pressure resistance in arteries & veins
(A) Aldosterone-secreting tumor • Opposes filtration (favors
(B) Adrenal adenoma secreting aldosterone and cortisol
Capillary
absorption);
(C) Pheochromocytoma Oncotic 28mmHg
• increased by increases in
(D) Left renal artery stenosis Pressure
plasma protein concentration
(E) Right renal artery stenosis 3-49. Costanzo LS. BRS Physiology. 7 ed. 2019 th

• Opposes filtration (favors


The L renal artery stenosis means less blood in the left kidney, which Interstitial
absorption);
means less blood pressure in the L kidney. This will stimulate the macula Hydrostatic -3mmHg
• slightly negative due to
densa in the L kidney, triggering R-A-A-S. This would result in increased Pressure
BP. The increased aldosterone would cause negative feedback on renin lymphatic pump
production on the R kidney (the normal kidney) but not on the L kidney Interstitial • Favors filtration;
(the abnormal kidney) resulting in decreased renin on the R and Oncotic • determined by interstitial 8mmHg
increased renin on the L. Pressure protein concentration
Dr. Banzuela
• Hydraulic conductance of
Effects of ACE-I include the following: decreased arteriolar capillary wall (capillary
vasoconstriction (decreased arteriolar resistance), increased sodium
Filtration permeability;promotes
excretion by the kidneys to the urine, decreased cardiac output -
Dr. Banzuela Coefficient filtration)
• Formula: permeability X
3.7 MICROCIRCULATION AND LYMPH surface area
EXCHANGE OF SUBSTANCES ACROSS CAPILLARIES Normal Net
-- 2mL/ min
Filtration
TYPE MECHANISM EXAMPLE
Simple diffusion ✔GUIDE QUESTIONS
Lipid-Soluble O2 and CO2 In a capillary, Pc is 30mmHg, Pi is –2mmHg, πc is 25mmHg, and πi is
across capillary
Substances 2mmHg. What is the direction of fluid movement and the net driving
endothelial cells
force?
Small Water- clefts (pores) water, glucose,
(A) Absorption; 6 mm Hg
Soluble between amino acids (B) Absorption; 9 mm Hg
Substances endothelial cells (C) Filtration; 6 mm Hg
Large Water- (D) Filtration; 9 mm Hg
Soluble pinocytosis Proteins (E) There is no net fluid movement
3-13. Costanzo LS. BRS Physiology. 7th ed. 2019
Substances
In a capillary, Pc is 30mmHg, Pi is –2mmHg, πc is 25mmHg, and πi is
Wag niyo deadmahin yung nakasulat sa taas. Lipid-soluble substances – simple 2mmHg. If Kf is 0.5 mL/min/mm Hg, what is the rate of water flow across
diffusion across capillaries. Small water-soluble substances – clefts/pores across the capillary wall?
capillaries. Large water-soluble substances – pinocytosis (cellular drinking). (A) 0.06 mL/min (D) 9.00 mL/min
Dr. Banzuela (B) 0.45 mL/min (E) 18.00 mL/min
✔GUIDE QUESTION (C) 4.50 mL/min 3-14. Costanzo LS. BRS Physiology. 7 ed. 2019 th

Which of the following substances crosses capillary walls primarily Water flow = K f × Net pressure
through water-filled clefts between the endothelial cells? = 0.5 mL/min/mm Hg × 9 mm Hg
(A) O2 (C) CO = 4.5 mL/min
(B) CO2 (D) Glucose Dr. Banzuela
3-47. Costanzo LS. BRS Physiology. 7th ed. 2019
LYMPHATIC SYSTEM
Listed to the audio recording while reading the next section on Starling Forces:
• 2-3 Liters of lymph produced per day
• Has one-way valves, flow is unidirectional
STARLING FORCES • Functions:
https://qrs.ly/wtebiqq o Reabsorbs proteins and excess fluid back to the circulatory system
o Absorbs fat (using lacteals)
o Contains lymph nodes
Dr. Banzuela
STARLING FORCES • Lymph Flow is increased by
• Describes fluid movement into (absorption) or out of (filtration) o Massage secondary to extremity muscle contractions
the capillary o Negative intrathoracic pressure during inspiration
• Starling forces are listed below. Take note: Intravenous pressure o Suction effect of high velocity flow of blood in the veins
(IV pressure) is NOT a starling force o Increased capillary permeability
• Lymph Flow will be decreased if there is an increase in: Capillary
Oncotic Pressure (remember lymph flow is proportional to
capillary filtration)
EDEMA
• Excess fluid in the interstitial spaces beyond the capability of the
lymphatic system to return into the blood vessels
CAUSES OF EDEMA EXAMPLES
• Arteriolar dilatation
• Venous constriction
© ↑ Capillary
Topnotch Medical Board Prep • ↑ venous pressure
STARLING EQUATION Hydrostatic
• Heart failure
• Fluid Movement (Jv) Pressure
• ECF volume expansion
o if Positive, promotes filtration (fluid moves out of the capillary) • Standing
o If Negative, promotes absorption (fluid moves into the capillary)
• âplasma protein concentration
↓ Capillary Oncotic • Severe liver disease
Pressure • Protein malnutrition
• Nephrotic syndrome
• Burns
↑ Filtration
• Inflammation (due to release of
Coefficient
histamine, cytokines)

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Focus on the causes of edema above. Importante lahat yan. Some key points: Refer to the text above about Autoregulation of blood flow as you listed to
Right-Sided heart failure btw will cause PERIPHERAL edema, while Left-Sided this audio recording:
heart failure will cause PULMONARY edema. Kwashiorkor syndrome (a form of
protein malnutrition) can cause edema because of decreased albumin synthesis
AUTOREGULATION
resulting in decreased capillary oncotic pressure.
Pulmonary edema can cause death by suffocation in 20-30 minutes in severe acute
OF BLOOD FLOW
left heart failure. https://qrs.ly/hyebir8
Safety factors against edema: Low Tissue compliance in the negative pressure
ranges, lymph flow driven by tissue pressure, protein washout by the lymph Dr. Banzuela

(decreased proteins in the interstitial fluids when lymph flow increases) • Long-term Control
Dr. Banzuela
o Via Angiogenesis
✔GUIDE QUESTION § Due to Vescular Endothelium Growth Factor (VEGF),
The tendency for edema to occur will be increased by Fibroblast Growth Factor (FGF), Angiogenin
(A) arteriolar constriction - a drug that can stimulate production of VEGF receptors is of
(B) increased venous pressure value in the treatment of Coronary Artery Disease as it
(C) increased plasma protein concentration
would help bypass blocked arteries
(D) muscular activity 3-22. Costanzo LS. BRS Physiology. 7 th ed. 2019
§ Occurs in response to hypoxia
Determinant of venous pressure: Neck veins o Vascularity is determined by Maximum Blood Flow Need, not
Dr. Banzuela
by average need
§ A lot of capillary beds are closed most of the time, and only
3.8 SPECIAL CIRCULATIONS open needed
CONTROL OF BLOOD FLOW
EXTRINSIC CONTROL OF BLOOD FLOW
• Maybe Intrinsic (Local) or Extrinsic (Hormonal/Humoral)
• Through
REASONS FOR LOCAL CONTROL OF BLOOD FLOW o Sympathetic Nervous System
• For the tissues to get their proper amounts of oxygen and o Vasoactive Hormones
nutrients and to remove wastes
HORMONAL / HUMORAL MECHANISMS FOR BLOOD FLOW CONTROL
• For thermoregulation (e.g., in the skin)
VASOCONSTRICTORS VASODILATORS
• For homeostasis (e.g., kidneys)
• Vasopressin: most • Prostacyclin (PGI2):
BLOOD FLOW TO DIFFERENT ORGANS potent vasoconstrictor counteracts TXA2
AND TISSUES UNDER BASAL CONDITIONS • Nitric Oxide (NO): vasodilates
mL/min upstream blood vessels
Percent mL/min
100g o MOA: guanylate cyclase and
Brain 14 700 50 cGMP
• Serotonin: released
Heart 4 200 70 o Acetylcholine causes
because of blood vessel
Bronchi 2 100 25 vasodilation by increasing
damage; causes
Kidneys 22 1100 360 production of NO in vascular
arteriolar
Liver 27 1350 95 smooth muscle
vasoconstriction;
Portal (21) 1050 o Acetylcholine causes
implicated in migraine
Arterial (6) 300 VASOCONSTRICTION instead
Muscle (inactive state) 15 750 of vasodilation whenever the
Bone 5 250 3 endothelium is damaged due
Skin (cool weather) 6 300 3 to decreased NO
Thyroid gland 1 50 160 • Endothelin: released by
• PGE: vasodilators
Adrenal glands 0.5 25 300 damaged endothelium
Other tissues 3.5 175 1.3 • Lactate, Adenosine: found in
• PGF and TXA2
TOTAL 100.0 5000 muscles
MECHANISMS FOR LOCAL BLOOD FLOW CONTROL • Bradykinin & Histamine: causes
• Acute Control • Norepinephrine, arteriolar dilation & venous
o Decreased tissue oxygenation will increase blood flow Epinephrine constriction leading to increased
o Mechanisms for Acute Control of Local Blood Flow filtration (local edema)
§ Myogenic Theory: when vascular smooth muscle are • Angiotensin II • H+, CO2, K, ANP
stretched, there’s a reflex contraction and vice versa Memorize the vasoconstrictors and vasodilators listed above. Key points:
- May explain autoregulation, but not active or reactive hyperemia ADH is the most powerful vasoconstrictor of them all – it’s also called
§ Metabolic Theory: vasodilator metabolites (Adenosine, CO2, VASOPRESSIN to remind you it’s a vasoconstrictor. Thromboxane A2 has 2
H+, K+, lactate) are produced as a result of metabolic activity effects: vasoconstriction and platelet aggregation. Its natural inhibitor is
increasing blood flow during hypoxia PROSTACYCLIN. Lactic Acid is a vasodilator released by muscles lacking
oxygen (it makes sense that it’s a vasodilator – to give more blood, oxygen
• Acute Control: Examples of Metabolic Theory and glucose to the starving muscles). Lactic Acid can stimulate pain nerve
o Reactive Hyperemia endings – lactic acid is the cause of chest pain in M.I. and muscle pain in
§ ↑ in blood flow in response to brief period of ↓ blood flow muscle fatigue. Lactic Acid is a product of ANAEROBIC glycolysis.
§ e.g. if vessels blocked for a few seconds to an hour → blood Dr. Banzuela

flow increases 4-7x the normal ✔GUIDE QUESTION


o Active Hyperemia Which of the following is an effect of histamine?
§ Blow flow increases to meet increased metabolic demand (A) Decreased capillary filtration
§ e.g. In exercising muscle, G.I. glands during hypersecretory (B) Vasodilation of the arterioles
period, brain during rapid mental activity (C) Vasodilation of the veins
(D) Decreased Pc
• Acute Control: Autoregulation of Blood Flow
(E) Interaction with the muscarinic receptors on the blood vessels
o Brain: CO2 and H+ 3-38. Costanzo LS. BRS Physiology. 7th ed. 2019
§ an increase will cause vasodilation to wash out excess CO2 Carbon dioxide (CO2) regulates blood flow to which one of the following organs?
o Heart: Perfusion Pressure (A) Heart (D) Skeletal muscle at rest
§ If perfusion pressure to the heart is suddenly decreased, (B) Skin (E) Skeletal muscle during exercise
3-39. Costanzo LS. BRS Physiology. 7 ed. 2019
(C) Brain th

compensatory vasodilation of arterioles would occur to


Blood flow to which organ is controlled primarily by the sympathetic
maintain constant flow nervous system rather than by local metabolites?
§ Highest coronary blood flow per gram of Left ventricular (A) Skin (C) Brain
myocardium occurs during: beginning of diastole (B) Heart (D) Skeletal muscle during exercise
o Kidneys: Tubuloglomerular Feedback 3-42. Costanzo LS. BRS Physiology. 7th ed. 2019

§ Macula densa in the distal tubule detects fluid levels Characteristics of cerebral blood flow (CBF): CBF related to metabolism of
§ Afferent arteriole constriction/dilation occurs to maintain cerebral tissues, H+ causes increased blood flow (vasodilation), O2 utilization by
appropriate renal blood flow and GFR the brain is within narrow limits, increased CBF will increase removal of acids.
Dr. Banzuela

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SUMMARY OF CONTROL OF SPECIAL CIRCULATIONS


Circulation* (% of
Local Metabolic Vasoactive
Resting Cardiac Sympathetic Control Mechanical Effects
Control Metabolites
Output)
Most important Hypoxia Mechanical compression
Coronary (5%) Least important mechanism
mechanism Adenosine during systole
Increases in intracranial
Most important CO2
Cerebral (15%) Least important mechanism pressure decrease cerebral
mechanism H+
blood flow
Most important Lactate Most important mechanism at rest Muscular activity causes
Muscle (20%) mechanism during K+ (α1 receptor causes vasoconstriction; temporary decrease in blood
exercise Adenosine β2 receptor causes vasodilation) flow
Least important Most important mechanism
Skin (5%)
mechanism (temperature regulation)
Most important Hypoxia
Pulmonary+ (100%) Least important mechanism Lung inflation
mechanism vasoconstricts
Adapted from Costanzo LS. BRS Physiology. 7th ed. 2019.
Take note of the various vasoactive metabolites involved in various organs above (e.g., hypoxia and adenosine for the heart, CO2 and H+ for brain, etc.)
Dr. Banzuela

3.9 GRAVITY, EXERCISE AND HEMORRHAGE HEMORRHAGE


• ↑ Baroreceptor Reflex → ↑ HR, ↑ SV, ↑ TPR, ↑ vasoconstriction of
STANDING
veins (↑ VR) → ↑BP
• Blood pools in the veins → ↓ VR → ↓ CO → ↓BP
• ↑ RAAS activation → ↑ Na+ reabsorption → ↑ intravascular volume → ↑ BP
• ↓ Baroreceptor stretch → ↓ firing rate of CN IX → ↑ Sympathetic
• ↓ Systemic Capillary Hydrostatic Pressure → ↑ fluid absorption →
Outflow
↑ intravascular volume → ↑ BP
• ↑ HR, ↑ SV → ↑ CO → ↑ BP
• Vasoconstriction of systemic arterioles → ↑ TPR → ↑BP Compensatory response to hemorrhage: Increased Renin, Aldosterone,
Epinephrine, Heart rate, etc.
• Vasoconstriction of Veins → ↑VR → ↑CO → ↑BP Dr. Banzuela

✔GUIDE QUESTIONS
When a person moves from a supine position to a standing position, 4. RESPIRATORY PHYSIOLOGY
which of the following compensatory changes occurs?
1. Functional Anatomy of the 6. CO2 Transport
(A) Decreased heart rate
Respiratory System 7. Pulmonary Circulation
(B) Increased contractility
2. Lung Volumes and Capacities 8. V/Q Defects
(C) Decreased total peripheral resistance (TPR)
3. Mechanics of Breathing 9. Control of Breathing
(D) Decreased cardiac output
4. Gas Exchange 10. Integrated Responses to the
(E) Increased PR intervals
3-2. Costanzo LS. BRS Physiology. 7th ed. 2019 5. Oxygen Transport Respiratory System
A 24-year-old woman presents to the emergency department with severe
diarrhea. When she is supine (lying down), her blood pressure is 90/60
mm Hg (decreased) and her heart rate is 100 beats/min (increased).
4.1 FUNCTIONAL ANATOMY OF THE RESPIRATORY
When she is moved to a standing position, her heart rate further SYSTEM
increases to 120 beats/min. Which of the following accounts for the RESPIRATORY SYSTEM
further increase in heart rate upon standing?
(A) Decreased total peripheral resistance
• UPPER AIRWAYS: Nose, Sinuses, Larynx
(B) Increased venoconstriction • LOWER AIRWAYS: Trachea, Airways, Alveoli
(C) Increased contractility • Ultimate goal of respiratory system: Gas Exchange to give
(D) Increased afterload adequate O2 and remove CO2
(E) Decreased venous return
3-48. Costanzo LS. BRS Physiology. 7th ed. 2019 NOSE
EXERCISE • FUNCTIONS: Warms, humidifies, & filters air, smell, defense
• ↑ Sympathetic outflow → ↑ HR, ↑ SV → ↑ CO → ↑ blood flow to The nostrils cause “air conditioning” during inspiration (unlike breathing
skeletal muscles through the mouth) – it will warm the air (cold air can damage respiratory lining),
o during exercise, blood flow to: humidify the air (dry air can damage the respiratory lining, the water vapor can
§ Brain (cerebral blood flow): remains constant act as lubricant) via the capillaries of the nose, filter the air (preventing large
§ Heart (coronary blood flow), skin: increased particles from obstructing/damaging the respiratory lining), and is involve in the
special sense of smell (which also has an impact in terms of taste)
§ Gut, kidneys, non-exercising muscles: decreased Dr. Banzuela
• Increase in cardiac output during exercise is due to a LARGE SINUSES
increase in heart rate and a SMALL increase in stroke volume • Frontal sinuses, Maxillary sinus, Sphenoid sinus, Ethmoid sinus
• Vasoconstriction of splanchnic and renal arterioles → ↑ blood o Surround nasal passageways
flow to skeletal muscles • FUNCTIONS: Lighten the skull & offer resonance to voice
• Vasoconstriction of veins → ↑ VR → ↑ CO → ↑ blood flow to skeletal
muscles
• ↑vasodilator metabolites → vasodilation of skeletal muscle
arterioles → ↓ TPR → ↑blood flow to skeletal muscle
✔GUIDE QUESTION
During exercise, total peripheral resistance (TPR) decreases because of
the effect of
(A) the sympathetic nervous system on splanchnic arterioles
(B) the parasympathetic nervous system on skeletal muscle arterioles
(C) local metabolites on skeletal muscle arterioles
(D) local metabolites on cerebral arterioles
(E) histamine on skeletal muscle arterioles
3-24. Costanzo LS. BRS Physiology. 7th ed. 2019
Which of the following parameters is decreased during moderate
exercise?
(A) Arteriovenous O2 difference
(B) Heart rate
(C) Cardiac output
(D) Pulse pressure
(E) Total peripheral resistance (TPR)
3-43. Costanzo LS. BRS Physiology. 7th ed. 2019

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LARYNX BRONCHIOLE
• MAJOR STRUCTURES • Terminal Bronchiole vs Respiratory Bronchiole: Respiratory
o Vocal Cords: Protects the airway form choking, Produces sounds Bronchiole is capable of Gas Exchange
used for speech • (+) presence of Respiratory Epithelium
o Epiglottis, Arytenoids: Covers vocal cords during swallowing o Maintains periciliary fluid so that cilia may function

© Topnotch Medical Board Prep


TRACHEA
• In the trachea, C-shaped cartilages are found anteriorly

© Topnotch Medical Board Prep

GOBLET CELLS, • Produces Mucus


SUBMUCOSAL • Hyperplasia, Hypertrophy seen in
GLANDS chronic smokers
• Non—ciliated cells of the respiratory
CLARA CELLS epithelium
© Topnotch Medical Board Prep
(CLUB CELLS) • Produces protective GAGs and
Why C-shaped and not “O-shaped”? So that when you swallow, the bolus metabolize air-borne toxins
will cause “dilations” in the esophagus that will compress on the trachea DUST CELLS
• Blood element that removes particles
(the part without the cartilage) – this helps prevent aspiration). (ALVEOLAR
trapped in the alveoli
Dr. Banzuela
MACROPHAGES)
COUGH REFLEX (STEPS):
1. 2.5 Liters of air rapidly inspired
2. Epiglottis closes
3. Abdominal muscles contract
4. Epiglottis opens
• SNEEZE REFLEX
o Initiating stimulus: Irritation of the nasal passageways
o Similar to cough reflex but applied to nasal passageways (upper
respiratory passageways)
o With depression of the uvula
LUNGS
• Weighs 1kg
o 60% lung tissue
o 40% blood
• Alveolar Spaces
o Responsible for most of lung’s volume
© Topnotch Medical Board Prep
o Divided by lung interstitium
TRACHEA, BRONCHI, BRONCHIOLES
• Gas Exchange Area: 70-85 m2
• Trachea → Main Stem Bronchi → Lobar Bronchi → Segmental Bronchi • RIGHT LUNG
→→→ Terminal bronchioles → Respiratory bronchiole → Alveoli o 3 Lobes (Upper, Middle, Lower)
o Right vs Left: Right bronchi is wider, shorter, and more o Oblique Fissure, Horizontal Fissure
vertical (hence it is more prone to aspiration of material)
• LEFT LUNG
o 2 Lobes (Upper, Lower)
o Oblique Fissure

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This handout is only valid for October 2023 PLE batch. This will be rendered obsolete for the next batch since we update our handouts regularly.
DESCRIPTION ANSWER
• Anatomic + Alveolar Dead Space.
PHYSIOLOGIC
Normally EQUAL to Anatomic Dead
DEAD SPACE
Space Value
FUNCTIONAL
• Bronchopulmonary Segments
ANATOMIC UNIT
(segmental bronchi to alveoli)
OF THE LUNG
• Respiratory bronchiole, alveolar ducts,
alveolar sacs
These are the only 3 areas in the respiratory RESPIRATORY
system capable of gas exchange. Be careful
UNIT OF THE
with terminal bronchiole vs. respiratory
bronchiole – respiratory bronchiole is the first LUNG
part of the respiratory unit of the lung capable
of gas exchange. Not terminal bronchiole.
Dr. Banzuela

• For gas exchange TYPE I


• Larger than Type II PNEUMOCYTE
© Topnotch Medical Board Prep
• For surfactant production TYPE II
• VISCERAL PLEURA • Smaller than Type I PNEUMOCYTE
• PARIETAL PLEURA • Produces mucus for lubrication in the
GOBLET CELLS
• PLEURAL FLUID respiratory system
o Found in potential space between the two pleura • Produces protective GAGs and CLARA CELLS /
o Keeps the 2 pleura together (allows them to slide) metabolize air-borne toxins CLUB CELLS
o Has negative pressure • Alveolar Macrophages DUST CELLS
When you see the term “dead space” in physio, it means an area with no gas
ALVEOLI exchange. Normal Anatomic dead space is 150mL – physiologically, there
TYPE DESCRIPTION FUNCTION is no gas exchange from the nose to the trachea to the terminal bronchioles.
• 96-98% of Normal Alveolar Dead Space meanwhile is 0mL – physiologically, all alveoli
should be capable of gas exchange, therefore alveolar dead space should
surface area
Type I ideally be zero. Physiologic dead space is just the sum of anatomic dead
• thin, flat, does • Gas Exchange space and alveolar dead space.
Pneumocyte
NOT secrete Dr. Banzuela

surfactant • Physiologic Dead Space: (calculated using BOHR EQUATION):


• 2-4% of surface • For Surfactant
area production
• Small, cuboidal, o Decreases surface
Type II
found at corners tension
Pneumocyte
of alveoli (preventing
• May turn into alveolar collapse)
Type I if needed
Rupture of the alveolar walls occur at any positive pressure in the • Minute Ventilation:
interstitial spaces greater than alveolar pressure (> 0 mmHg) that causes
dumping of fluid from the interstitial spaces to the alveoli
Dr. Banzuela • Alveolar Ventilation:

Alveolar Ventilation is also called CORRECTED MINUTE VENTILATION.


Its formula is basically minute ventilation minus physiologic dead space.
Dr. Banzuela

✔GUIDE QUESTION
A healthy 65-year-old man with a tidal volume (TV) of 0.45 L has a
breathing frequency of 16 breaths/min. His arterial PCO2 is 41 mm Hg,
and the PCO2 of his expired air is 35 mm Hg. What is his alveolar
ventilation?
(A) 0.066 L/min (D) 6.14 L/min
(B) 0.38 L/min (E) 8.25 L/min
4-17. Costanzo LS. BRS Physiology. 7 ed. 2019
(C) 5.0 L/min th

Computation:
© Topnotch Medical Board Prep
VA = (VT-VD) x RR
4.2 LUNG VOLUMES AND CAPACITIES VD = VT x (PaCO2 x PeCO2)/PaCO2
SPECIAL NOTES ON RESPIRATORY PHYSIOLOGY = (0.45) x (41-35)/41
=0.066L
DESCRIPTION ANSWER VA = (0.45 – 0.066L) x 16 = 6.14L/min
• Air from the Nose to Terminal
Bronchioles (conducting zone) that does ANATOMIC LUNG VOLUMES AND CAPACITIES
NOT undergo gas exchange DEAD SPACE • Air in lungs is divided into:
• (Normal Value: 150 mL) o Lung Volumes: IRV, TV, ERV, RV
o Lung Capacities: Sum of 2 or more lung volumes:
• Air in the respiratory unit of the lung § IC, FRC, VC, TLC
(respiratory zone) that does NOT • Lung volumes and Capacities: 20-25% lower in females
undergo gas exchange due to V/Q
ALVEOLAR • if a person is at rest, arrangement of lung volume and capacities
mismatch from highest to lowest volume: TLC > VC > IC > IRV > FRC > ERV
DEAD SPACE
• (Normal Value: 0 mL) and RV > TV
• Causes of increased alveolar dead space:
Asthma, emphysema, bronchitis

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This handout is only valid for October 2023 PLE batch. This will be rendered obsolete for the next batch since we update our handouts regularly.

While you look at this figure, watch this


video on lung volumes and capacities:

LUNG VOLUMES
AND CAPACITIES
https://qrs.ly/u4ebirq
Dr. Banzuela

© Topnotch Medical Board Prep

TERM DESCRIPTION ✔GUIDE QUESTIONS


• Air inspired over and above the tidal volume Which volume remains in the lungs after a maximal expiration?
IRV (A) Tidal volume (TV)
• Utilized during exercise
(B) Vital capacity (VC)
• Amount of air inhaled or exhaled during the (C) Expiratory reserve volume (ERV)
relaxed state. (D) Residual volume (RV)
TV • Normal Value: 500mL divided into: (E) Functional residual capacity (FRC) From Physiology BRS, 6 Edth

o anatomic dead space (150mL) In a maximal expiration, the total volume expired is
o respiratory unit of the lung (350mL) (A) tidal volume (TV)
• Amount of air exhaled after expiration of tidal (B) vital capacity (VC)
ERV (C) expiratory reserve volume (ERV)
volume
(D) residual volume (RV)
• Remaining air in the lungs after maximal (E) functional residual capacity (FRC) From Physiology BRS, 6 Edth

exhalation
RV
• Maintains oxygenation in between breaths FEV1 AND FVC
• Cannot be measured by spirometry • FEV1: volume of air expired after one second of forced maximal
IC • TV + IRV exhalation
• ERV + RV; air in the lungs after expiring tidal • FVC: total volume of air expired of forced maximal exhalation
volume • FEV1/FVC: normal value: 80%
• Equilibrium/resting volume of the lung OBSTRUCTIVE LD RESTRICTIVE LD
FRC • Marker for lung function (e.g., COPD) (e.g., Fibrosis)
• During this time, alveolar pressure = FEV1 ↓↓ ↓
atmospheric pressure FVC ↓ ↓↓
• Cannot be measured by spirometry
• IRV + TV + ERV FEV1/FVC ↓ Normal or ↑
VC or
• Maximum volume of air that can be inhaled or FRC ↑ ↓
FVC
exhaled The table above is very important. Obstructive Lung Diseases (OLD) have
• IRV + TV + ERV + RV problems with EXPIRATION, typical examples are asthma and COPD.
TLC
• Cannot be measured by spirometry Restrictive Lung Diseases (RLD) have problems with INSPIRATION, typical
example is lung fibrosis. In both OLD and RLD, FEV1 and FVC would
✔GUIDE QUESTIONS decrease, but at different rates. In OLD, there is a greater decrease in FEV1
Which of the following lung volumes or capacities can be measured by than FVC, while for RLD, there is a greater decrease in FVC rather than
spirometry? FEV1. These would result in a decrease in FEV1/FVC ratio in OLD (since
(A) Functional residual capacity (FRC) mathematically, pag mas mataas yung pagbagsak ng numerator kaysa sa
(B) Physiologic dead space denominator, bababa yung quotient) and normal or increase FEV1/FVC
(C) Residual volume (RV) ratio in RLD (since mathematically, pag mas mataas yung pagbagsak ng
(D) Total lung capacity (TLC) denominator kaysa sa numerator, tataas yung quotient). Wag
(E) Vital capacity (VC) From Physiology BRS, 6 Ed th
makakalimutan: decreased FEV1/FVC ratio in OLD and increased
A spirometer is a device that can measure exhaled air. RV and lung FEV1/FVC ratio in RLD.
Dr. Banzuela
capacities that have RV in its formula (namely FRC and TLC), cannot be
measured by a spirometer. Physiologic dead space (made up of • Primary drive to breath in COPD patients: Hypoxic Drive (low
anatomic and alveolar dead spaces) cannot also be measured using a PaO2 stimulating peripheral chemoreceptors. Hypercapneic
spirometer, we use Bohr Equation for physiologic dead space drive is blunted due to compensated respiratory acidosis)
computation. • Plmonary function test results in person with pulmonary fibrosis
Dr. Banzuela
(restrictive lung disease): Decreasing diffusing capacity of the
Which volume remains in the lungs after a tidal volume (TV) is expired?
(A) Tidal volume (TV)
lung
(B) Vital capacity (VC) • Drugs that can cause interstitial lung disease/restrictive lung
(C) Expiratory reserve volume (ER) disease: Busulfan, amiodarone, methotrexate
(D) Residual volume (RV) • Charcot-Leyden Crystals (microscopic crystals composed of
(E) Functional residual capacity (FRC) eosinophil protein galectin-10) are seen in patients with Asthma
(F) Inspiratory capacity or Parasitic Pneumonia
(G) Total lung capacity From Physiology BRS, 6 Ed
• Characteristics of asthma:
th

If I change the question to the volume in the lungs after maximal


expiration, the answer would be residual volume. Be careful and read
o bronchoconstriction (spastic contraction of bronchiolar smooth
the question thoroughly. I recommend you underline key words in the muscles) and increased mucus production.
questions in the medical board exams. o Problem with EXPIRATION rather than INSPIRATION
Dr. Banzuela o FRC increased during asthma attack
A 35-year-old man has a vital capacity (VC) of 5 L, a tidal volume (TV) of o IgE high
0.5 L, an inspiratory capacity of 3.5 L, and a functional residual capacity o Drugs for asthma: beta-2 adrenergic agonists
(FRC) of 2.5 L. What is his expiratory reserve volume (ERV)?
(A) 4.5 L (D) 3.0 L
(B) 3.9 L (E) 1.5 L
From Physiology BRS, 6 Ed
(C) 3.6 L th

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4.3 MECHANICS OF BREATHING • Law of Laplace


MUSCLES INVOLVED IN PULMONARY VENTILATION
• Inspiration
o Normal Inspiration: Active (main muscle: Diaphragm)
§ diaphragm descends, ribs move upward and outward,
lungs become wider and taller
o Forced Inspiration (occurs during exercise): External
Intercostals, Accessory Muscles: SCM, Anterior Serrati,
Scalene, Alae Nasi, Genioglossus, Arytenoid
o Ribs move upward and outward; abdominal contents move
downward
• Expiration
o Normal Expiration: Passive
o Forced Expiration (occurs during exercise): Internal
Intercostals, Abdominal muscles (Rectus Abdominis, Internal
and External Oblique, Transversus Abdominis)
o Ribs move downward and inward; abdominal contents move
upward
Again, with feelings. Main muscle for normal inspiration: diaphragm.
Main muscle for normal expiration: none. EXTERNAL intercostals are for
forced INSPIRATION. INTERNAL intercostals are for forced
EXPIRATION. Wag mapagbaligtad ha. ACCESSORY Muscles are used also © Topnotch Medical Board Prep
for forced inspiration, while ABDOMINAL Muscles are used also for forced • Pre-Term Babies have high collapsing pressure due to:
expiration. o Smaller alveolar radius (50 micrometers) compared to adults
Dr. Banzuela
o Lack mature surfactant
COMPLIANCE OF THE LUNGS • In comparison to term infant, Pre-term infant has:
• Distensibility of the lungs and chest wall o INCREASED pulmonary vascular resistance, pulmonary artery
• Change in volume for a given change in pressure (analogous to pressure (PAP), pulmonary capillary hydrostatic pressure,
capacitance of vessels) pressure gradient from pulmonary artery to the aorta
• Inversely related to elastance o DECREASED Pulmonary Blood Flow
• Slope of the press-volume curve Remember the Law of Laplace. Collapsing pressure (P) is directly
proportional to surface tension (T) and inversely proportional to radius of
o Inspiration has a different curve than expiration due to need to
the alveoli (r). In pre-term babies, perfect storm – walang mature
overcome surface tension forces during inspiration (hysteresis) surfactant kaya mataas ang surface tension; at the same time pre-term nga
o Highest compliance: at middle range of pressures kaya maliit yung mga alveoli. High T and Low r = very high P. That very
o Lowest compliance: at high pressures (curve flattens here) high collapsing pressure causes neonatal respiratory distress syndrome
Surfactant decreases surface tension which PREVENTS alveolar collapse
(decreased collapsing pressure)
Dr. Banzuela
LUNG SURFACTANT
DESCRIPTION ANSWER
Cells that produces
TYPE II PNEUMOCYTES
surfactant
Main component of
WATER
Surfactant
Active component of DIPALMITOYL-
Surfactant PHOSPHATIDYLCHOLINE (DPPC)
Mechanism for DPPC
AMPHIPATHIC NATURE
reducing surface
© Topnotch Medical Board Prep (HYDROPHOBIC AND HYDROPHILIC)
tension
• Lungs: has natural tendency to collapse
• Chest wall: has a natural tendency to expand Effect of Surfactant on
INCREASE
Lung Compliance
• At FRC: lungs and chest wall are at equilibrium
Start of Surfactant
o Intrapleural pressure is negative 24TH WEEK AOG
production
• Pneumothorax (presence of gas in pleural space)
o Intrapleural pressure = atmospheric pressure Maturation of
35TH WEEK AOG
Surfactant
§ Lungs on affected side collapses, chest wall expands
§ V/Q ratio decreases Deficiency in NEONATAL RESPIRATORY
§ Trachea shifts AWAY FROM THE AFFECTED LUNG surfactant causes DISTRESS SYNDROME (RDS)
• Atelectasis (collapse of lung parenchyma) AMNIOTIC
o Trachea shifts TOWARDS THE AFFECTED LUNG Test for Surfactant LECITHIN:SPHINGOMYELIN RATIO
(RATIO OF 2:1 OR GREATER = MATURE
FETAL LUNGS)
CLINICAL CONDITIONS
Treatment for
• Emphysema STEROIDS, SURFACTANT
newborn RDS
o Lung compliance is increased → new, higher FRC will be seen
to balance tendency of chest wall to expand vs tendency of lungs LUNG SURFACTANT
to collapse → patient becomes barrel-chested • Helps prevent alveolar collapse
• Fibrosis • Produced by Type II Alveolar Cells
o Lung compliance is decreased → new, lower FRC will be seen • Mixture of DPPC, other lipids and proteins
to maintain balance • Decreased in the lungs of chronic smokers
o Remember: Lung Compliance is inversely related to the elastic
✔GUIDE QUESTION
recoil properties of the lung An infant born prematurely in gestational week 25 has neonatal
• Covid-19 respiratory distress syndrome. Which of the following would be expected
o Marked by high respiratory drive and abnormal compliance in this infant?
(not specific to Covid-19) (A) Arterial PO2 of 100 mm Hg
(B) Collapse of the small alveoli
(C) Increased lung compliance
SURFACE TENSION (D) Normal breathing rate
• Force caused by water molecules at the air-liquid interface that (E) Lecithin:sphingomyelin ratio of greater than 2:1 in amniotic fluid
tends to minimize surface area From Physiology BRS, 6th Ed

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AIRWAY RESISTANCE BREATHING CYCLE


• Described by Poiseuille Law • Remember: lung pressures are expressed relative to atmospheric
pressure
o At FRC, alveolar pressure = 0
• Before inspiration:
o Intrapleural pressure is negative, alveolar pressure = 0
• During inspiration:
o Intrapleural pressure becomes more negative, alveolar
pressure becomes more negative
• Major site of airway resistance: medium-sized bronchi • During expiration:
(controversial: largest bronchi in Guyton and Hall) o Alveolar pressure increases and becomes greater than
• Airway resistance is increased by bronchial smooth muscle atmospheric pressure
contraction, decreased if lungs are removed and inflated by saline o Intrapleural pressure increases back to its resting value
and affected by work of breathing (see image below) When you inhale, the contraction of the diaphragm will
• The 3 Factors affecting Airway Resistance: cause a decrease in intrapleural pressure which will cause a decrease in
alveolar pressure. That drop in alveolar pressure will cause the alveolar
o Bronchial Smooth Muscle Contraction/Relaxation due to ANS:
pressure to be less than atmospheric pressure → this will lead to air moving
§ alters radius of airways from the atmosphere and into the alveoli. During expiration, intrapleural
o Lung Volume pressure will increase which will cause an increase in alveolar pressure.
§ due to radial traction exerted on airways by surrounding lung tissue The alveolar pressure will now become greater than atmospheric pressure
§ High lung volumes → greater traction, decreased airway causing air to move from alveoli to the atmosphere.
resistance Dr. Banzuela

§ asthmatic patients “learn” to breathe at higher volumes to


offset airway resistance
o Viscosity/Density of inspired gas
§ Low-density gas (e.g. helium) reduces resistance to airflow

© Topnotch Medical Board Prep


✔GUIDE QUESTION
Which of the following is the site of highest airway resistance?
(A) Trachea (D) Smallest bronchi
(B) Largest bronchi (E) Alveoli
From Physiology BRS, 6 Ed
(C) Medium-sized bronchi th

BRONCHIAL SMOOTH MUSCLES © Topnotch Medical Board Prep


CAUSES ✔GUIDE QUESTION
CAUSES BRONCHODILATION
BRONCHOCOSTRICTION Which of the following is true during inspiration?
Sympathetic Nervous system Parasympathetic Nervous (A) Intrapleural pressure is positive
(adrenergic) System (cholinergic) (B) The volume in the lungs is less than the functional residual capacity
Atropine Cool air, exercise (FRC)
(C) Alveolar pressure equals atmospheric pressure
Vasointestinal Peptide (VIP) Irritants (e.g., sulfur dioxide) (D) Alveolar pressure is higher than atmospheric pressure
Leukotrienes, Histamine (E) Intrapleural pressure is more negative than it is during
Remember the factors that causes bronchodilation and bronchoconstriction expiration From Physiology BRS, 6 Ed th

above.
Dr. Banzuela

4.4 GAS EXCHANGE


PERTINENT LAWS OF PHYSICS FOR RESPIRATORY PHYSIOLOGY
𝑷𝟏 𝑽𝟏 = 𝑷𝟐 𝑽𝟐 • Law implying that an ↑ in Lung
Boyle Law
𝑷𝒙 = 𝑷𝑩 × 𝑭 Volume will ↓ Pressure
𝑃𝑎𝑟𝑡𝑖𝑎𝑙 𝑝𝑟𝑒𝑠𝑠𝑢𝑟𝑒 = 𝑇𝑜𝑡𝑎𝑙 𝑝𝑟𝑒𝑠𝑠𝑢𝑟𝑒 ×
Dalton Law of Partial Pressure 𝐹𝑟𝑎𝑐𝑡𝑖𝑜𝑛𝑎𝑙 𝑔𝑎𝑠 𝑐𝑜𝑛𝑐𝑒𝑛𝑡𝑟𝑎𝑡𝑖𝑜𝑛
• Law for Mixed Gases
𝑪𝒙 = 𝑷𝒙 × 𝒔𝒐𝒍𝒖𝒃𝒊𝒍𝒊𝒕𝒚
Henry Law for Concentration of Where:
Cx = concentration of dissolved gas (mL gas/100mL blood) • Law for Gases dissolved in solution
Dissolved Gases Px = Partial pressure of gas (mmHg)
Solubility = Solubility of gas in blood (mL gas/100mL blood/mmHg
𝑫𝑨 ∆𝑷 • Law for transfer of gases through simple
𝑽𝒙 = ∆𝒙
diffusion in cell membranes or capillary
Where: Vx = Volume of gas transferred per unit time walls
Fick Law of Diffusion D = diffusion coefficient of the gas A = surface area • Driving force for diffusion: Partial
ΔP = partial pressure difference of the gas Pressure difference (NOT
Δx = thickness of the membrane concentration of gases)
• Gas exchange from alveoli into the blood uses PASSIVE DIFFUSION

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PARTIAL PRESSURES OF O2 AND CO2 (mmHg)
Dry Humidified Tracheal
Gas Alveolar Air Systemic Arterial Blood Mixed Venous Blood
Inspired Air Air
150 100 Slightly <100 40
PO2 160 (Addition of water vapor (O2 has diffused due to equilibration & (O2 has diffused to tissues
decreases PO2) decreasing PO2) “physiologic shunt” decreasing PO2)
40 40 46
PCO2 0 0 (CO2 has been added due to equilibration with (CO2 has diffused from
increasing PCO2 alveolar air tissues increasing PCO2)
A major cause of cor pulmonale in COPD is a decrease in: Alveolar PO2; NOT a sign of cor pulmonale: CYANOSIS
✔GUIDE QUESTION 4.5 OXYGEN TRANSPORT
If an area of the lung is not ventilated because of bronchial obstruction,
the pulmonary capillary blood serving that area will have a PO2 that is HEMOGLOBIN (HgB)
(A) equal to atmospheric PO2 • Oxygen (O2):
(B) equal to mixed venous PO2 o 98%: transported via hemoglobin (Hgb)
(C) equal to normal systemic arterial PO2 § Hgb has the greatest effect on the ability of blood to
(D) higher than inspired PO2 transport oxygen
(E) lower than mixed venous PO2 § Contain highest proportion of stored oxygen in the body
From Physiology BRS, 6th Ed
§ Normal values: For men, 13.5 to 17.5 grams per deciliter. For
ALVEOLAR-BLOOD GAS EXCHANGE women, 12.0 to 15.5 grams per deciliter
• Perfusion-limited Gas Exchange o 2%: transported freely dissolved in plasma
o Gas equilibrates with the pulmonary capillary near the start of
Nooks and Crannies. Been covered before several times in the med boards:
the pulmonary capillary
HgB normal values: For men, 13.5 to 17.5 grams per deciliter. For
o Diffusion of gas increased only by increasing blood flow women, 12.0 to 15.5 grams per deciliter
o e.g., N2O, O2, CO2 under normal conditions Dr. Banzuela
• Hemoglobin can bind with oxygen (oxyhemoglobin), carbon
monoxide (carboxyhemoglobin) or carbon dioxide
(carbaminohemoglobin)
o Carbon Monoxide poisoning has the greatest reduction in O2
delivery to the tissues
o Characteristic of CO poisoning: normal PaO2, lower than
normal Arterial O2 saturation
• Oxygen normally binds with Fe2+(ferrous state) and not
Fe3+(ferric state)
• Adult Hemoglobing (HbA): 𝝰2𝝱2 (2 alpha chains, 2 beta chains)
• Fetal Hemoglobin (HbF): 𝝰2𝝲2 (2 alpha chains, 2 gamma chains)
• Hemoglobin S: 𝛼*+ 𝛽*,
• 2,3 BPG binds more to HbA and binds less with HbF
o O2 affinity is higher in HbF than HbA (shift to the left of the O2-
© Topnotch Medical Board Prep

• Diffusion-limited Gas Exchange HgB dissociation curve)


o Gas Does NOT equilibrate even until the end of the pulmonary o Facilitates release of O2 from mother to fetus
capillary • O2-binding capacity
o CO and O2 during strenuous exercise and disease states o Maximum amount of O2 that can be bound to Hgb
(emphysema, fibrosis) o Measured at 100% saturation
o Expressed in mL O2/gram of hemoglobin
o Normal value: 1.34mL
Nooks and Crannies: Amount of O2 carried by 1 gram of HgB: 1.34mL =)
Suki yan sa med boards several times na according to student feedback.
Dr. Banzuela

• O2 content of the blood


o Total amount of O2 carried in blood, including bound and
dissolved O2
𝑂* 𝑐𝑜𝑛𝑡𝑒𝑛𝑡 = (ℎ𝑒𝑚𝑜𝑔𝑙𝑜𝑏𝑖𝑛 𝑐𝑜𝑛𝑐𝑒𝑛𝑡𝑟𝑎𝑡𝑖𝑜𝑛 × 𝑂* 𝑏𝑖𝑛𝑑𝑖𝑛𝑔 𝑐𝑎𝑝𝑎𝑐𝑖𝑡𝑦
× %𝑠𝑎𝑡𝑢𝑟𝑎𝑡𝑖𝑜𝑛) + 𝐷𝑖𝑠𝑠𝑜𝑙𝑣𝑒𝑑 𝑂*
Remember: 2,3 BPG binds more to adult Hgb and binds less with HbF. 2,3
BPG binds to an allosteric site in Hgb and cause a shift to the right of the
O2-HgB dissociation curve – it causes O2 to unbind with Hgb. The
mechanism for transfer of O2 from mother to fetus is through 2,3 BPG.
Watch this video on the O2-HgB dissociation curve first, then read and
highlight the corresponding portions below:

O2-HGB DISSOCIATION CURVE


https://qrs.ly/hbebis2

Dr. Banzuela
© Topnotch Medical Board Prep O2-HgB DISSOCIATION CURVE
Movement of oxygen from alveoli to blood at rest (normal condition) is • Sigmoidal in shape
PERFUSION-LIMITED – meaning mabilis naman yung pag transfer ng gas o PO2 of 25 mmHg: 50% saturated (P50)
from alveoli to blood, ang limitation is the number of capillaries and the
o PO2 of 40 mmHg: 75% saturated (mixed venous blood)
blood inside it. See the graph of perfusion-limited exchange above – ang
bilis maachieve yung peak early sa length ng capillary. o PO2 of 100 mmHg: almost 100% saturated (arterial blood)
• Exhibits Positive Cooperativity
Movement of oxygen from alveoli to blood during exercise is DIFFUSION-
o Binding of first O2 molecule increases affinity for second O2
LIMITED – the limiting factor is the diffusion characteristics of the gas
itself, and not blood anymore. In exercise kasi, tumataas yung blood flow to molecule and so forth
the lungs, so hindi na perfusion-limited ang gas exchange during exercise.
Take a look at the graph of diffusion-limited gas exchange above – kahit
patapos na ng length ng capillary, hindi pa rin mataas yung peak, kasi nga
even with increased blood flow doon, hindi naman nagbabago yung
diffusing characteristics ng oxygen itself.
Dr. Banzuela

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This handout is only valid for October 2023 PLE batch. This will be rendered obsolete for the next batch since we update our handouts regularly.

PAO2, PaO2, PACO2, PaCO2. Don’t get confused by the capital letter “A” and
the small letter “a.” Capital letter A is for “Alveolar”, small letter “a” is for
arterial. (mnemonic: “A” comes before “a”, “alveolar” comes before
“arterial” alphabetically) A-a gradient therefore is the difference between
Alveolar PO2 and Arterial PO2. Ideally A-a gradient should be zero, because
of Oxygen will diffuse across the alveolar membrane, it should do so until
the alveoli and the blood equilibrate (equal pressures). But the normal A-
a gradient is actually around 10mmHg – meaning mas mataaas slightly
yung alveolar PO2 sa arterial PO2. Why? Because there are areas in the
lungs that receives less/little blood flow (“bypass areas”) compared to the
rest. That’s why the normal A-a gradient is not 0mm.
Dr. Banzuela

© Topnotch Medical Board Prep CAUSES OF HYPOXEMIA


SHIFT TO THE Cause PaO2 A-a Gradient
SHIFT TO THE RIGHT
LEFT High altitude (↓PBàPAO2) Decreased Normal
Increased Hypoventilation (↓P PAO2) Decreased Normal
Attachment of Increased UNLOADING
BINDING of O2 Diffusion defect (e.g., fibrosis) Decreased Increased
O2 to Hgb of O2 from Hgb
from Hgb V/Q defect Decreased Increased
P50 Increased Decreased Right-to-left shunt Decreased Increased
Carbon DIOXIDE, A-a gradient = difference in PO2 between alveolar gas and arterial blood; PB =
Acidosis (Bohr Effect), Carbon barometric pressure; PAO2 alveolar PO2; PaO2 = arterial PO2; V/Q =
Causes ventilation/perfusion ratio
2,3 BPG, Exercise & MONOXIDE, HbF Adapted from Costanzo LS. BRS Physiology. 7th ed. 2019.
Temperature CAUSES OF HYPOXIA
CAUSE MECHANISM
↓ cardiac output ↓ blood flow
↓ PaO2 causes ↓ % saturation of
Hypoxemia
hemoglobin
↓ hemoglobin concentration causes ↓ O2
Anemia
content of blood
Carbon monoxide ↓ O2 content of blood and left shift of
poisoning hemoglobin - O2 dissociation curve
Cyanide poisoning ↓ O2 utilization by tissues
PaO2 = arterial PO2
Adapted from Costanzo LS. BRS Physiology. 7th ed. 2019.
The two tables above are very important. Remember the causes of
hypoxemia with increased A-a gradient (pag tumaas yung A-a gradient, it
means there’s a problem transferring O2 from alveoli to blood). Remember
also the causes of hypoxia – hypoxemia take note is just one of them.
Dr. Banzuela

✔GUIDE QUESTIONS
Which of the following causes of hypoxia is characterized by a decreased
arterial PO2 and an increased A–a gradient?
(A) Hypoventilation
(B) Right-to-left cardiac shunt
(C) Anemia
(D) Carbon monoxide poisoning
© Topnotch Medical Board Prep
(E) Ascent to high altitude From Physiology BRS, 6 Ed th

• *CO: binds 250x better to Hgb than O2, decreases O2 content of Which person would be expected to have the largest A–a gradient?
blood and causes shift to the left of O2-Hgb dissociation curve (A) Person with pulmonary fibrosis
HYPOXEMIA VS. HYPOXIA (B) Person who is hypoventilating due to morphine overdose
HYPOXEMIA HYPOXIA (C) Person at 12,000 feet above sea level
Decreased arterial PO2 Decreased tissue PO2 (D) Person with normal lungs breathing 50% O2
(E) Person with normal lungs breathing 100% O2
Not always caused by
Will lead to hypoxia From Physiology BRS, 6th Ed
hypoxemia Again, hypoxemia with high A-a gradient: diffusion defect like lung
A-a gradient used to Triggers: EPO production fibrosis, V/Q defect, and R-to-L shunting of the blood.
differentiate between causes (through increased Dr. Banzuela

of hypoxemia production of hypoxia-


inducible factor 1𝝰) 4.6 CO2 TRANSPORT
Hypoxemia can lead to hypoxia but not all cases of hypoxia are caused by • Transported in 3 Forms:
hypoxemia. Hypoxemia – low ARTERIAL PO2. Hypoxia – low TISSUE PO2. o 70%: HCO3-
Hyperventilation from hypoxemia is caused by: Peripheral o 23%: CarbaminoHgb
Chemoreceptors (the carotid and aortic body chemoreceptors) o 7%: freely-dissolved in plasma
Dr. Banzuela
Alveolar-Arterial (A-a) GRADIENT • Deoxyhemoglobin buffers H+ inside RBCs
• Difference between Alveolar PO2 and Arterial PO2 • Note that reaction 1 in the equation shown primarily occurs in
PLASMA (although it can also occur inside RBCs)
• Carbonic Acid (via carbonic acid-bicarbonate system) is the
principal buffer in the interstitial fluid
Oxygen in the blood is transported two ways: mainly (98%) via Hgb (as
Oxyhemoglobin) and partly as a freely-dissolved substance (2%). CO2 is
transported in the blood three ways: mainly (70%) as chemically converted
substance HCO3-, partly as a substance bound to Hgb or CarbaminoHgb
(23%), and partly (7%) as a freely-dissolved substance in blood.
Dr. Banzuela

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This is the immortal bicarbonate buffer system! =) the reaction facilitated


by carbonic anhydrase on CO2 and H2O inside the RBC is also seen inside the
parietal cells (refer to the GI module).
Dr. Banzuela

© Topnotch Medical Board Prep

Refer to the audio recording below while looking at the picture above about
Haldane and Bohr Effect:

HALDANE AND BOHR EFFECT


https://qrs.ly/r2ebisa
Dr. Banzuela

© Topnotch Medical Board Prep

✔GUIDE QUESTIONS ✔GUIDE QUESTION


In the transport of CO2 from the tissues to the lungs, which of the In which vascular bed does hypoxia cause vasoconstriction?
following occurs in venous blood? (A) Coronary (D) Muscle
(A) Conversion of CO2 and H2O to H+ and HCO3– in the red blood (B) Pulmonary (E) Skin
From Physiology BRS, 6 Ed
cells (RBCs) (C) Cerebral th

(B) Buffering of H+ by oxyhemoglobin Compared with the systemic circulation, the pulmonary circulation has a
(C) Shifting of HCO3– into the RBCs from plasma in exchange for Cl– (A) higher blood flow (D) higher capillary pressure
(D) Binding of HCO3– to hemoglobin (B) lower resistance (E) higher cardiac output
From Physiology BRS, 6 Ed
(E) Alkalinization of the RBCs From Physiology BRS, 6 Ed th (C) higher arterial pressure th

The pH of venous blood is only slightly more acidic than the pH of arterial Watch the video as you refer to the discussion below about Lung Zones:
blood because
(A) CO2 is a weak base
(B) there is no carbonic anhydrase in venous blood LUNG ZONES
(C) the H+ generated from CO2 and H2O is buffered by HCO3– in venous https://qrs.ly/yxebisj
blood
(D) the H+ generated from CO2 and H2O is buffered by
deoxyhemoglobin in venous blood Dr. Banzuela
(E) oxyhemoglobin is a better buffer for H+ than is deoxyhemoglobin 3 POSSIBLE LUNG ZONES
From Physiology BRS, 6th Ed

4.7 PULMONARY CIRCULATION


PULMONARY CIRCULATION
DESCRIPTION ANSWER
Pulmonary Circulation:
< SYSTEMIC CIRCULATION
PRESSURE
Pulmonary Circulation:
< SYSTEMIC CIRCULATION
RESISTANCE
Pulmonary Circulation:
= SYSTEMIC CIRCULATION
CARDIAC OUTPUT
Pulmonary Blood Flow: SAME THROUGH THE
SUPINE ENTIRE LUNG © Topnotch Medical Board Prep

Pulmonary BLOOD FLOW: LOWEST AT THE APEX, • Zone 1


STANDING HIGHEST AT THE BASE o Local Alveolar Capillary Pressure < Alveolar Air Pressure
Effect of Hypoxia (low PAO2) throughout the cycle
VASOCONSTRICTION • Zone 2
on Pulmonary Arterioles
Causes of Pulmonary Global HIGH ALTITUDE, FETAL o Local Alveolar Capillary Systolic Pressure > Alveolar Air
Hypoxic Vasoconstriction CIRCULATION Pressure during systole but less than that during diastole
Other Lung Vasoactive • Zone 3
TXA2, PGI2 o Local Alveolar Capillary Pressure > Alveolar Air Pressure
Substances
Causes Bronchoconstriction LEUKOTRIENES throughout the cycle
Remember: Lung “Zones” do not refer to areas (Zone 1 is not the apex, Zone
Hypoxia causes VASOCONSTRICTION in the pulmonary arterioles (to
2 is not the middle part, Zone 3 is not the base. Lung Zone are SCENARIOS,
shunt blood towards better ventilated areas of the lungs) and
not areas.
VASODILATION in the systemic arterioles (to give more oxygen to Dr. Banzuela
hypoxic tissues). Pulmonary arterioles kasi PICK-UP oxygen while systemic
LUNG ZONES
arterioles GIVE UP oxygen. Be careful about this. Also – the leukotrienes
DESCRIPTION ANSWER
that cause bronchoconstriction in ASTHMA are your LTC4, D4, E4 – these
Apex of the Lungs (standing)
are collectively called the Slow-Reactive Substance of Anaphylaxis (SRS-A). ZONE 2, ZONE 3
Base of the Lungs (standing)
That’s why we use steroids to decrease asthma attacks – to decrease these ZONE 3
Entire lungs In a Supine
leukotrienes. Asthma bronchoconstriction is due to SRS-A and not due to
histamine. ZONE 3
Position
Dr. Banzuela
Entire lungs During exercise ZONE 3
Pulmonary Hemorrhage and
ZONE 1
Positive Pressure Ventilation
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SHUNTS ✔GUIDE QUESTIONS
• Right-to-Left Shunts Low V/Q here means mababa yung ventilation, or mataas yung
o Normal to a small extent since 2% of cardiac output bypasses perfusion or both. So, if you give O2, naimprove mo yung oxygenation ng
lungs blood (at dahil pwedeng mataas yung perfusion, mas appreciated yung
o Abnormal conditions (e.g., TOF) results in hypoxemia supplemental O2). Hindi pwedeng E yung sagot dito – no ventilation
means no effect at all with supplemental O2.
• Left-to-Right Shunts
o More common than right-to-left shunts (e.g., PDA) Again: Oxygen most beneficial in which scenario: decreased or low V/Q
Dr. Banzuela
o Does not cause hypoxemia; PO2 will be elevated on the R side of
What happens to V/Q ratio from apex to base during exercise? A: Becomes
the heart
uniform (not variable) throughout the lungs.
During exercise there is increased pulmonary blood flow (increased
4.8 V/Q DEFECTS perfusion) causing equalization of the ventilation-perfusion ratio
V/Q RATIO from base to apex
• V: Ventilation (Alveolar Ventilation) Dr. Banzuela

• Q: Perfusion (Pulmonary Blood Flow)


• Normal V/Q Ratio: 0.8 4.9 CONTROL OF BREATHING
o Results in: PO2 = 100mmHg, PCO2 = 40mmHg COMPONENTS FOR CONTROL OF BREATHING
• High V/Q: high PO2, low PCO2 (e.g., lung apex) • Cerebral Cortex
• Low V/Q: low PO2, high PCO2 (e.g., lung base) • Control Centers in the medulla and Pons
• V/Q = Zero • Central and Peripheral Chemoreceptors
o Shunt (e.g., R-L shunt, airway obstructions) • Mechanoreceptors
• V/Q = infinite • Respiratory Muscles
o Dead Space (e.g., pulmonary embolism)
• In an upright position, which area of the lung will have a HIGHER CEREBRAL CORTEX
compliance: Base of the Lungs • Can override the autonomic brainstem centers
• Voluntary Hyperventilation
o ↓ PaCO2 → ↑ pH → LOC
• Voluntary Hypoventilation (breath-holding)
o ↓ PaO2, ↑ PaCO2 → ↓ pH → LOC

CONTROL CENTERS IN THE MIDBRAIN, PONS


MEDULLA PONS
Creates the Basic Respiratory Modifies the Basic
Rhythm Respiratory Rhythm
Reticular formation of
medulla contains the Dorsal
Respiratory Group (DRG), contains the Apneustic and
Ventral Respiratory Group Pneumotaxic centers
(VRG) and Central
© Topnotch Medical Board Prep
Chemoreceptors
Refer to the picture above as we discuss V and Q: main respiratory centers send
out regular busts of impulses
to inspiratory muscles
V AND Q during quiet respiration and --
https://qrs.ly/yxebivg are affected by impulses
from pain receptors and the
Dr. Banzuela cerebral cortex
✔GUIDE QUESTIONS
When a person is standing, blood flow in the lungs is
(A) equal at the apex and the base
(B) highest at the apex owing to the effects of gravity on arterial
pressure
(C) highest at the base because that is where the difference
between arterial and venous pressure is greatest
(D) lowest at the base because that is where alveolar pressure is
greater than arterial pressure
From Physiology BRS, 6th Ed
A 49-year-old man has a pulmonary embolism that completely blocks
blood flow to his left lung. As a result, which of the following will occur?
(A) Ventilation/perfusion (V/Q) ratio in the left lung will be zero
(B) Systemic arterial PO2 will be elevated
(C) V/Q ratio in the left lung will be lower than in the right lung
(D) Alveolar PO2 in the left lung will be approximately equal to the
PO2 in inspired air
(E) Alveolar PO2 in the right lung will be approximately equal to the
PO2 in venous blood From Physiology BRS, 6 Ed th © Topnotch Medical Board Prep

Because no blood flow → no gas exchange. Alveolar PO2 with therefore be CONTROL
DESCRIPTION
the same as inspired air (hindi pumupunta oxygen from alveoli to blood) CENTER
Dr. Banzuela
Main Respiratory Center •
Compared with the apex of the lung, the base of the lung has
(A) a higher pulmonary capillary PO2 generates basic rhythm for breathing •
(B) a higher pulmonary capillary PCO2 for Normal/Resting Inspiration •
(C) a higher ventilation/perfusion (V/Q) ratio Input: CN IX (peripheral • DRG
(D) the same V/Q ratio chemoreceptors) and CN X (peripheral
From Physiology BRS, 6 Ed th

A person with a ventilation/perfusion (V/Q) defect has hypoxemia andchemoreceptors and lung
is treated with supplemental O2. The supplemental O2 will be most mechanoreceptors)
helpful if the person’s predominant V/Q defect is • Output: phrenic nerve → diaphragm
(A) dead space (D) low V/Q
(B) shunt (E) V/Q=0 • Supplements effect of DRG during
(C) high V/Q (F) V/Q=× exercise
VRG
From Physiology BRS, 6 Ed • for forced inspiration and expiration
th

(overdrive mechanism)
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CONTROL MECHANORECEPTORS
DESCRIPTION
CENTER DESCRIPTION MECHANORECEPTORS
• Pacemaker Neurons responsible for • Stimulated by Lung Distension
respiratory rhythmogenesis: VRG Pre- • Initiates Hering-Breuer Reflex LUNG STRETCH
Botzinger Complex that decreases Respiratory Rate RECEPTORS
• Location: Upper Pons PNEUMOTAXIC by prolonging expiratory time
• Shortens time for inspiration → ↑ RR CENTER • Stimulated by Limb Movement
JOINT & MUSCLE
• Location: Lower Pons • Causes anticipatory increase in
RECEPTORS
• Prolongs time for inspiration → ↓ RR APNEUSTIC Respiratory Rate during Exercise
• Causes deep and prolonged inspiratory CENTER • Stimulated by Noxious chemicals
gasp (apneusis) • Causes bronchoconstriction and IRRITANT RECEPTORS
The respiratory centers (DRG, VRG) are found in the MEDULLA. The one increases the Respiratory Rate
that modifies the output of the respiratory centers (Pneumotaxic, • Found in “juxtacapillary” areas
Apneustic Centers) are found in the PONS. DRG is the MAIN respiratory • Stimulated by pulmonary
center, VRG merely supplements during exercise. Pneumotaxic Center – capillary engorgement
think “pneumonia” – pampabilis ng paghinga – it increases respiratory • Causes rapid shallow breathing
rate. Apneustic center – think “apnea” – pampabagal ng paghinga – it J RECEPTORS
and responsible for the feeling of
decreases respiratory rate.
dyspnea (e.g., in Left-sided heart
Role of mechanical ventilator: decrease the work of breathing until failure)
patients no longer needs it
Dr. Banzuela • Responsible for the feelings of
CENTRAL AND PERIPHERAL CHEMORECEPTORS dyspnea
• Central Chemoreceptors Here’s a mnemonic – J receptors detect what? Jyspnea! =)
o Location: ventral medulla Dr. Banzuela

o Respond directly to CSF H+ ✔GUIDE QUESTION


o Causes ↑ RR Hypoxemia produces hyperventilation by a direct effect on the
(A) phrenic nerve
(B) J receptors
(C) lung stretch receptors
(D) medullary chemoreceptors
(E) carotid and aortic body chemoreceptors From Physiology BRS, 6 Ed th

© Topnotch Medical Board Prep

• Peripheral Chemoreceptors
o Location: Carotid and Aortic Bodies
§ drug that stimulates the carotid bodies would cause ↓ PCO2 in
arterial blood due to peripheral chemoreceptors
o Responds MAINLY to PaO2 <60mmHg
§ Possibly due to excitable Glomus Cells (also seen in central
chemoreceptors)
- Glomus Cell Action Potential: ↑ PCO2/↓ PO2 → ↓ potassium
efflux → opening of voltage-gated calcium channels →
Calcium Influx → Secretion of NTs (e.g. Ach, NE, dopamine,
Substance P, met-enkephalin)
o Causes ↑ RR
o Also respond to high PaCO2, high arterial H+ (low plasma pH)
§ Intravenous lactic acid increases ventilation by stimulating
the peripheral chemoreceptors © Topnotch Medical Board Prep
MNEMONICS CHEMORECEPTORS 4.10 INTEGRATED RESPONSES OF THE
Central Chemoreceptors = CSF H+ (stated another way, low pH RESPIRATORY SYSTEM
in the CSF. This is caused by high PaCO2) RESPIRATORY RESPONSES TO EXERCISE
Peripheral Chemoreceptors = Pang Low Oxygen (O2) INCREASES (↑) DECREASES (↓) NO CHANGE
Remember the LOCATIONS, TRIGGERS and ACTIONS of Central and • O2 Consumption • Arterial pH • Arterial PO2 and
Peripheral chemoreceptors. We will discuss this again during the lecture • CO2 Production (strenuous PCO2
videos. • Respiratory Rate exercise due to • Arterial pH
Dr. Banzuela
• Venous PCO2 lactic acidosis) (moderate
✔GUIDE QUESTION • Pulmonary exercise)
A 42-year-old woman with severe pulmonary fibrosis is evaluated by her Blood Flow
physician and has the following arterial blood gases: pH = 7.48, PaO2 = 55
mm Hg, and PaCO2 = 32 mm Hg. Which statement best explains the • Type of reached at workloads that is >60% of maximal workload
observed value of PaCO2? marked by increased muscle lactic acid production, decreased
(A) The increased pH stimulates breathing via peripheral arterial pH, increased alveolar ventilation: Anaerobic Exercise
chemoreceptors PO2 and PCO2 do NOT change during moderate exercise due to
(B) The increased pH stimulates breathing via central chemoreceptors compensatory mechanisms like tachypnea. They might change during
(C) The decreased PaO2 inhibits breathing via peripheral STRENUOUS exercise.
chemoreceptors Dr. Banzuela
(D) The decreased PaO2 stimulates breathing via peripheral
✔GUIDE QUESTION
chemoreceptors
(E) The decreased PaO2 stimulates breathing via central Which of the following changes occurs during strenuous exercise?
chemoreceptors From Physiology BRS, 6 Ed th
(A) Ventilation rate and O2 consumption increase to the same
extent
Remember: hypoxemia is the main trigger for peripheral chemoreceptors. (B) Systemic arterial PO2 decreases to about 70 mm Hg
The hypoxemia here (PaO2=55mmHg) stimulated the peripheral (C) Systemic arterial PCO2 increases to about 60 mm Hg
chemoreceptors. Peripheral chemoreceptors in turn increased the (D) Systemic venous PCO2 decreases to about 20 mm Hg
respiratory rate (RR). The increased RR is then responsible for the decrease (E) Pulmonary blood flow decreases at the expense of systemic blood
in PaCO2 (PaCO2=32mmHg). flow
Dr. Banzuela From Physiology BRS, 6th Ed

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This handout is only valid for October 2023 PLE batch. This will be rendered obsolete for the next batch since we update our handouts regularly.
RESPIRATORY RESPONSES TO HIGH ALTITUDE o Question
INCREASES (↑) DECREASES (↓) § 67/M cardiac transplant candidate has the following labs:
• Respiratory Rate • Alveolar PO2 Pulmonary Artery Pressure (PAP) = 35mmHg, Cardiac Output
• Arterial pH • Arterial PO2 = 4L/min, Left Atrial Pressure(LAP) = 15mmHg, Right Atrial
• Hgb Concentration Pressure = 10mmHg
• 2,3 BPG § What is his PVR?
• Pulmonary Vascular Resistance o Answer
(Hypoxic vasoconstriction) § PVR = Mean PAP – mean LAP/pulmonary blood flow
§ = 35 – 15mmHg/4L/min
The table above is very important. If you go to a place of high altitude (e.g., § = 5mmHg/L/min
Baguio, the following may happen):
SHUNT FRACTION
The decreased alveolar PO2 is due to decreased barometric pressure. This
leads to decreased arterial PO2 (hypoxemia). (RATIO OF SHUNTED TO TOTAL PULMONARY BLOOD FLOW)
The increased ventilation rate (increased RR) is secondary to hypoxemia
(decreased arterial PO2), That hyperventilation will result in an increase in
arterial pH (Respiratory Alkalosis). During this time there is also an
increased in Hgb concentration due to increased EPO secretion (stimulated
by hypoxia). The increase in RBCs will cause an increase in 2,3 BPG. The
increased 2,3 BPG in turn will cause a shift to the RIGHT of the O2-HgB
dissociation curve (decreasing affinity of Hgb to O2 and increasing the P50).
Finally, Pulmonary vascular resistance is expected to INCREASE due to
HYPOXIC VASOCONSTRICTION – remember that lung hypoxia causes
pulmonary arteriolar VASOCONSTRICTION.
Dr. Banzuela
✔GUIDE QUESTIONS
A 38-year-old woman moves with her family from New York City (sea
level) to Leadville Colorado (10,200 feet above sea level). Which of the
following will occur because of residing at high altitude?
(A) Hypoventilation
(B) Arterial PO2 greater than 100 mm Hg © Topnotch Medical Board Prep
(C) Decreased 2,3-diphosphoglycerate (DPG) concentration
• Question:
(D) Shift to the right of the hemoglobin–O2 dissociation curve
o 32/M severe respiratory disease after aspiration pneumonia.
(E) Pulmonary vasodilation From Physiology BRS, 6 Ed th

Living in high altitude results in higher production of 2,3 BPG due to Inhaled NO given, and patient placed in prone position. Mean
reaction of the body to the low O2 pressure in the atmosphere. This pulmonary capillary oxygen content = 19mL/dL, Arterial O2
would cause a shift to the R of the O2-HgB dissociation curve. content = 18 mL/dL, Mixed Venous O2 content = 14 mL/dL,
Dr. Banzuela
Cardiac Output = 6L/min. What is the patient’s shunt fraction
A 12-year-old boy has a severe asthmatic attack with wheezing. He
(ratio of shunted to total pulmonary blood flow)?
experiences rapid breathing and becomes cyanotic. His arterial PO2 is 60
mm Hg and his PCO2 is 30 mm Hg. Which of the following statements • Answer:
about this patient is most likely to be true? o Shunt Fraction = (CCO2 – Ca2)/(CCO2-CvO2)
(A) Forced expiratory volume/forced vital capacity (FEV1/FVC) is o =(19mL/dL-18mL/dL)/(19mL/dL-14mL/dL)
increased o = 0.2
(B) Ventilation/perfusion (V/Q) ratio is increased in the affected areas OXYGEN CONSUMPTION VO2
of his lungs (CAN BE COMPUTED USING FICK EQUATION; SEE)
(C) His arterial PCO2 is higher than normal because of inadequate gas
exchange 𝑽𝑶𝟐 = 𝑪𝑶 × (𝑪𝒂𝑶𝟐 − 𝑪𝒗𝑶𝟐 )
(D) His arterial PCO2 is lower than normal because hypoxemia is
causing him to hyperventilate Please remember the formulas above – they’ve been utilized before in the
(E) His residual volume (RV) is decreased From Physiology BRS, 6 Ed th
med boards.
Dr. Banzuela
To treat this patient, the physician should administer Types of Hypoxia
(A) an α1-adrenergic antagonist
TYPE OF
(B) a β1-adrenergic antagonist CHARACTERISTICS
(C) a β2-adrenergic agonist HYPOXIA
(D) a muscarinic agonist Hypoxic (+) Alveolar hypoventilation (high PaCO2) and
(E) a nicotinic agonist From Physiology BRS, 6 Ed th Hypoxia hypoxemia (low PaO2)
↓ Hb (anemia) or ↓ saturation of hemoglobin
PRETEST EQUATIONS Anemic
with oxygen (SaO2) expected for a given PaO2
ALVEOLAR GAS EQUATION Hypoxia
(e.g., CO poisoning or methemoglobinemia)
Stagnant
↓ cardiac output
hypoxia
Histotoxic impaired O2 extraction → ↓ CaO2-CvO2 and ↑
Hypoxia SVO2

5. RENAL & ACID-BASE PHYSIOLOGY


1. Body Fluids
2. The Nephron, Reabsorption and Secretion, Renal Clearance, Renal Blood
© Topnotch Medical Board Prep Flow (RBF) and Glomerular Filtration Rate (GFR)
• Question: 3. K Regulation
o 36/M placed on ventilator with rate of 16, TV=600mL, FiO2 = 1.0 4. Renal Regulation of Urea, Phosphate, Calcium & Magnesium
o ABG reveals PO2=350mmHg, PCO2 = 36mmHg, pH = 7.32 At 5. Concentration and Dilution of Urine
barometric pressure = 757mmHg, with normal respiratory 6. Acid-Base Balance
exchange ratio (R) of 0.8, 7. Integrative Examples
o What is the patient’s alveolar oxygen tension?
5.1 BODY FLUIDS
• Answer:
o 665mmHg (PAO2=PIO2-(PaCO2/R) = (1.0) (757-47) - (36/0.8) = MNEMONIC “60-40-20” RULE
710-45 = 665mmHg 60% of BW: Water
• Pulmonary Vascular Resistance (PVR) Equation 40% of BW: ICF
20% of BW: ECF
Actually, ang tawag ko dito “60-40-20-15-5” rule. Kasi ECF can be
subdivided into Interstitial Fluid (IF) and Plasma. IF makes up 75% of ECF,
while plasma makes up 25% of ECF. So mathematically, 15% of your body
o Note: Left Atrial Pressure (LAP) above could be replaced by weight is IF, 5% of your body weight is plasma.
Pulmonary Capillary Wedge Pressure (PCWP); CO of R heart = Dr. Banzuela

Pulmonary Blood Flow


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TOPNOTCH MEDICAL BOARD PREP PHYSIOLOGY MAIN HANDOUT BY DR. ENRICO PAOLO C. BANZUELA
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% OF
MAJOR MAJOR ✔GUIDE QUESTIONS
COMPARTMENT BODY MARKERS
WEIGHT
CATIONS ANIONS A woman runs a marathon in 32°C weather and replaces all volume lost
in sweat by drinking distilled water. After the marathon, she will have
Titrated
Total Body (A) decreased total body water (TBW)
60% water, D2O, -- -- (B) decreased hematocrit
Water (TBW)
antipyrine (C) decreased intracellular fluid (ICF) volume
Extracellular (D) decreased plasma osmolarity
Sulfate,
Fluid (E) increased intracellular osmolarity From Physiology BRS, 6 Ed th

20% Inulin, Na+ Cl, HCO3-


Compartment Woman lost water + salt from sweating during the marathon. She was
Mannitol
(ECF) able to replace the water lost from sweating, but she was not able to
Radioactive replace the salt lost from sweating because she drank only distilled
Iodinated water. Her plasma osmolarity would therefore decrease since it might
5% have the same volume of water, but the is decreased Na concentration.
Serum
Plasma (25% Na+ Cl- HCO3- Dr. Banzuela
Albumin
of ECF) Watch these 3 videos as while analyzing the next diagram:
(RISA),
Evans Blue VOLUME AND CONCENTRATION CHANGES ACROSS
ECF- COMPARTMENTS
15%
Interstitial plasma
(75% Na+ Cl, HCO3-
Fluid (IF) volume
of ECF)
(indirect)
K+
(Mg2+ is Organic
Intracellular TBW-ECF
40% also an phosphate, PART 1 OF 3 PART 2 OF 3 PART 3 OF 3
Fluid (ICF) (indirect) ICF Protein https://qrs.ly/7qebivp https://qrs.ly/oqebivt https://qrs.ly/78ebivw
cation) Dr. Banzuela

Memorize the various “indicator molecules” or “markers” – they help


calculate the volume of the various body compartments. See guide question
below on how to compute for these volumes. Mannitol for example is a
marker for ECF, Evans Blue is marker for Plasma, Tritiated water is
marker for TBW. Wag dedmahin.
Total body water is lower in women, men or infants? A: women (due to fat).
55% women, 60% men, 70% neonate, 80% premature infants
Dr. Banzuela

✔GUIDE QUESTIONS
One gram of mannitol was injected into a woman. After equilibration, a
plasma sample had a mannitol concentration of 0.08 g/L. During the
equilibration period, 20% of the injected mannitol was excreted in the
urine. The subject’s
(A) extracellular fluid (ECF) volume is 1 L
(B) intracellular fluid (ICF) volume is 1 L
(C) ECF volume is 10 L
(D) ICF volume is 10 L
(E) interstitial volume is 12.5 L
ECF volume = amount of mannitol/concentration of mannitol
= 1 g – 0.2 g/0.08 g/L = 10 L.
From Physiology BRS, 6th Ed
Which of the following substances or combinations of substances could
be used to measure interstitial fluid volume?
(A) Mannitol (D) Inulin and D2O
(B) D2O alone (E) Inulin and radioactive albumin
From Physiology BRS, 6 Ed
(C) Evans blue th

Dietary reference value for and Na+ Cl-


per day – 3,100mg for adults
including pregnant and lactating women. Adequate intake of K+ per day
(no RDA) – 3,400mg for adult males, 2,600 for adult females, 2,900mg for
pregnant patients and 2,800mg for lactating women.
Dr. Banzuela

✔GUIDE QUESTIONS
Subjects A and B are 70-kg men. Subject A drinks 2 L of distilled water,
and subject B drinks 2 L of isotonic NaCl. As a result of these ingestions,
subject B will have a
(A) greater change in intracellular fluid (ICF) volume
(B) higher positive free-water clearance (CH2O)
(C) greater change in plasma osmolarity
(D) higher urine osmolarity
(E) higher urine flow rate From Physiology BRS, 6 Ed th

Subject A drinks water alone, subject B drinks water + salt. Therefore,


subject B will excrete more salt compared to subject A, resulting in © Topnotch Medical Board Prep
higher urine osmolarity.
Dr. Banzuela

ECF ICF PLASMA


TYPE EXAMPLES OSMOLARITY HCT
VOLUME VOLUME PROTEIN
Isosmotic volume contraction Diarrhea, burn ↓ NC NC ↑ ↑
Hyperosmotic volume Sweating, fever, diabetes
↓ ↓ ↑ NC ↑
contraction insipidus
Hypoosmotic volume
Adrenal insufficiency ↓ ↑ ↓ ↑ ↑
contraction
Isosmotic volume expansion Infusion of isotonic NaCl ↑ NC NC ↓ ↓
Hyperosmotic volume
High NaCl intake ↑ ↓ ↑ ↓ ↓
expansion
Hypoosmotic volume
SIADH ↑ ↑ ↓ NC ↓
expansion

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Daily Intake or Prolonged Heavy • NSAIDs block the renal protective
Normal
Output Exercise (in mL) prostaglandin synthesis → afferent
Intake arteriole constriction → ↓GFR → Acute
Water ingested 2,100 ? Kidney Injury (in low renal blood flow
Water from states)
200 200
metabolism • From PCT cells
Total Water Intake 2,300 ? • Promotes natriuresis
Output • At low doses: dilates interlobular
Dopamine
Insensible: skin 350 350 arteries, afferent arterioles, efferent
Insensible: lungs 350 650 arterioles → ↑ RBF
Sweat 100 5,000 • At high doses: acts as vasoconstrictor
Feces 100 100
Urine 1,400 500 RENAL CORPUSCLE – 3 CHARGE AND FILTRATION BARRIERS
Total Water Output 2,300 6,600 OF THE GLOMERULUS
• Capillary Endothelium
ESTIMATE FOR PLASMA OSMOLARITY o Highly-fenestrated with pores 8 nm in diameter
o Secrete NO and endothelin-1 (ET-1)
• Basement Membrane
o With type IV Collagen
o Main charge barrier
§ Destroyed in glomerular diseases
• Podocytes
True plasma osmolarity is difficult to determine since there are a lot of o Also called Bowman’s epithelial cells or visceral epithelium
solutes in plasma. A reasonable estimate, however, can be determined from o Contains foot processes and filtration slits
the 3 main solutes in there – sodium, glucose and BUN. See the formula
above.
Dr. Banzuela

5.2 NEPHRON, RENAL CLEARANCE,


RENAL BLOOD FLOW (RBF),
GLOMERULAR FILTRATION RATE (GFR)
Refer to the following videos as you go through the readings below

TYPES OF NEPHRONS
https://qrs.ly/6bebiw2
© Topnotch Medical Board Prep
Basis of the kidney’s filtering capacity:
Dr. Banzuela 1. Size (smaller the better)
NEPHRON 2. Charge (positively charged the better)
• Structural and Functional Unit of the Kidneys
The basement membrane of the renal corpuscle is clinically significant. It
• There are two major types of nephrons: is an anionic barrier (negatively-charged proteins are found here). It
• 75% of nephrons therefore prevents filtration of negatively-charged plasma proteins like
Cortical • Located in the renal cortex albumin. Destruction of the basement membrane would lead to
Nephron • With shorter Loops of Henle proteinuria (e.g., in nephrotic syndrome) since albumin is actually small
• Has peritubular capillaries enough to pass through the pores of the capillary endothelium.
Speaking of proteinuria: Orthostatic proteinuria is a benign condition
• 25% of nephrons marked by normal urinary protein excretion during the night but with
• Located in the corticomedullary junction increased excretion during the day, that is associated with activity and
Juxtamedullary
• With longer Loops of Henle upright posture (proteinuria <1g/24 hours).
• Has vasa recta Refer to the following videos as you go through the readings below
• What is therefore in renal cortex? Cortical nephron (more blood
compared to renal medulla)
RENAL CORPUSCLE
• A nephron has two major parts: https://qrs.ly/f7ebiwl
Renal or Afferent arterioles, glomerular capillaries,
Malpighian efferent arterioles, podocytes, mesangial
Corpuscle cells, JG cells, Bowman’s capsule & space Dr. Banzuela

Renal Tubules PCT, LH, DT, CD RENAL CORPUSCLE – OTHER CELLS


ENDOCRINE FUNCTION OF THE KIDNEYS • Mesangial Cells
o Intraglomerular: modified smooth muscles capable of
• From interstitial cells in peritubular
phagocytosis
capillary bed
§ Keeps the basement membrane free of debris by removing
• Controls the rate of RBC production
trapped residues and aggregated protein
Erythropoietin • Released in response to hypoxia →
§ Causes mesangial cell CONTRACTION: angiotensin II,
(EPO) stimulates RBC proliferation in bone
Arginine Vasopressin (AVP), Endothelin-1 (ET-1), Platelet-
marrow
derived growth factor (PDGF) and Platelet-Activating Factor
• Chronic kidney disease (CKD) causes ↓ (PAF)
EPO → chronic anemia § Causes mesangial cell RELAXATION: Atrial Natriuretic
• PCT converts 25-OH vitamin D3 → 1,25- Peptide (ANP), Nitric Oxide (NO)
(OH)2 vitamin D3 (calcitriol, active form) o Extraglomerular (Lacis Cells): may play role in renal
Calciferol
• Conversion is mediated by 1α- autoregulation, and RAAS
(Vitamin D)
hydroxylase (which is upregulated by • Juxtaglomerular (JG) Cells
PTH) o At the walls of afferent arterioles
• Effects of prostaglandins (PGE2 and PGI2) o Secrete renin
on the kidneys: Increased renal blood flow • Macula Densa
Prostaglandins and GFR o In DT
• Paracrine secretion vasodilates the afferent o Monitor Na+ concentration in the lumen of DT (and
arterioles → ↑RBF consequently, Blood Pressure)

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• (+) microvilli, convolutions
• Isosmotic fluid reabsorption: occurs in the PCT from lumen to
the PCT cell to peritubular capillaries
o Isosmotic since at the PCT, there is same ratio of Na and water
reabsorbed – 66%.
• Most susceptible to hypoxia, toxins
Remember: site for reabsorption of Na, H20, HCO3 and glucose: EARLY
Proximal tubule
Dr. Banzuela
LOOP OF HENLE
• Descending Limb
o Permeable to: water
o Impermeable to: solutes
• Ascending Limb
o Permeable to: solutes
o Impermeable to water
o Thick Ascending Limb of LH (TAL of LH)
o Na-K-2Cl symport seen here
§ One of the basis for countercurrent multiplier
o Also called the “diluting segment”
DISTAL TUBULE
• Early Distal Tubule (EDT)
o Also called the “cortical diluting segment”
o site of Macula Densa
• Late Distal Tubule (LDT)
o Principal Cells
§ Reabsorb: Na+ (and consequently water)
§ Secrete: K+
o Intercalated Cells
§ Reabsorb: K+
§ Secrete: H+
o Site of action of Aldosterone
o Dietary K+ has effect on K+ secretion/reabsorption
COLLECTING DUCT
© Topnotch Medical Board Prep
• Site of ADH action
Refer to the following videos as you go through the readings below
o ↑ ADH → ↑ aquaporin-2 channels → ↑water reabsorption
§ Results in ↑ intravascular volume → ↑VR, CO, BP
RENAL TUBULAR § Results in ↓ urine volume, ↑ urine concentration
SYSTEM Watch this as you read the section below:
https://qrs.ly/twebiz9
COUNTERCURRENT
Dr. Banzuela
TUBULAR SYSTEM MECHANISM
https://qrs.ly/o4ebizh
• Proximal Convoluted Tubule (PCT)
• Loop of Henle (LH) Dr. Banzuela
o Descending Limb of the Loop of Henle COUNTERCURRENT MECHANISM
o Thin Ascending Limb of the Loop of Henle • Countercurrent Multiplier: Loop of Henle
o Thick Ascending Limb of the Loop of Henle o Creates “graded osmolarity” in renal medulla
• Distal Tubule (DT) • Countercurrent Exchanger: Vasa Recta
o First Part: Early Distal Tubule o Preserves “graded osmolarity” in the renal medulla
o Second Part: Late Distal Tubule/Connecting Tubule, Cortical
Collecting Tubule
• Collecting Duct (CD)
o Medullary Collecting Tubule
o Collecting Duct

© Topnotch Medical Board Prep


Location Diuretic Example
Carbonic Anhydrase
PCT Acetazolamide
© Topnotch Medical Board Prep Inhibitor (CAI)
PCT LH Furosemide Loop Diuretic
• “workhorse” of the nephron hydrochlorothiazide
DT Thiazide Diuretic
o Reabsorption (HCTZ)
§ 66% of filtered Na+, K+, H2O Potassium-sparing
§ 100% of filtered glucose, amino acids CD Spironolactone
diuretic
o Secretion PCT to
§ Excess acids Osmotic diuretic Mannitol
CD
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Watch this as you read the section below: Secretion rate = Excretion Rate – Filtered Load
= 100 mg/min – 480mg/min
= -380mg/min
THE BASIC MOVEMENTS
Clearance rate = UV/P
INVOLVED IN URINE FORMATION
= (2500 mg/dL) (4 mL/min) / (400 mg/dL)
https://qrs.ly/2gebjdo
= 25 mL/min
Dr. Banzuela
Filtration Fraction = GFR/RPF
BASIC MOVEMENTS INVOLVED IN URINE FORMATION RPF = Clearance of PAH = UPAHVPAH/PPAH
• (Glomerular) Filtration *Since PAH values are not given for this example, FF cannot be computed.
However, in this context, if we must guess in the exam, filtration fraction is
o Movement from Glomerular Capillaries to Bowman’s Space ABOVE its normal average value of 20%. RPF and FF increases in DM,
• (Tubular) Reabsorption which leads to eventual increase in GFR
o Movement from Tubules to Interstitium to Peritubular Capillaries (https://www.uptodate.com/contents/diabetic-kidney-disease-pathogenesis-and-epidemiology)

• (Tubular) Secretion
o Movement from Peritubular Capillaries to Interstitium to Tubules
• Excretion
o Excretion = (Amount Filtered) – (Amount Reabsorbed) + (Amount
Secreted)
Normal urine volume of the bladder after urination of normal young adult
(normal Post-void Residual (PVR) urine): <50mL
Dr. Banzuela

© Topnotch Medical Board Prep


• Most solutes (e.g., glucose) actively reabsorbed or secreted
exhibit:
o Renal Threshold
§ Substance start to appear in the urine
§ Some nephrons exhibit saturation
o Renal Transport Maximum
© Topnotch Medical Board Prep § All excess substance appear in the urine
IMPORTANT FORMULAS § All nephrons exhibit saturation

SPECIAL NOTES ON TM CURVE


• Tm Curve of Glucose
o Normal: Filtered, 100% reabsorbed
• Where V = urine flow rate of substance (in mL/min) o Filtration: proportional to plasma glucose concentration
o Plasma = Plasma concentration of substance (in mg/dL) o Reabsorption of Glucose: occurs using SGLT-2 (Na-glucose
o Urine = urine concentration of substance (in mg/dL) cotranport) in PCT
• If filtered load > excretion rate: net reabsorption o Renal Threshold: plasma glucose 200mg/dL (some nephrons
• If filtered load < excretion rate: net secretion saturated)
o Renal Transport Maximum: plasma glucose > 375mg/dL (all
Another example of “nooks and crannies.” See those innocent-looking nephrons saturated)
formulas above (filtered load, excretion rate, reabsorption rate, secretion
rate)? It has always been there in the physio handout ever since. But it’s not o Splay: between 200mg/dL – 375mg/dL (glucose excretion
discuss intensively compared to other more commonly tested (and before complete saturation of all nephrons)
clinically important) formulas. So students tend to see, but not recall those • Tm Curve of PAH
formulas. Then those formulas were used for the med boards which o Normal: Filtered, Secreted, Not reabsorbed
shocked everyone. Please go through this handout with the mindset that
o Secretion of PAH occurs using carriers in the PCT
they are asking questions like these. Please also utilize the physio
flashcards based on physio BRS.
o Filtration load proportional to plasma PAH secretion
Dr. Banzuela o Secretion: also exhibits saturation
Example from Physio BRS: 50/F with untreated DM. GFR=120mL/min. Remember: the renal threshold for glucose: 200mg/dL – at this point, one
plasma glucose concentration = 400mg/DL, urine glucose concentration of nephron is already saturated (nephrons are not saturated all at the same
2500mg/dL, urine flow rate of 4mL/min. What is the rate of glucose time). Glucose can all be reabsorbed as long as plasma glucose is
filtered, reabsorbed, secreted and excreted? What is the clearance rate and <200mg/dL. The transport maximum for glucose: 375mg/dL (at this
filtration fraction? point, all nephrons are already saturated).
Dr. Banzuela

✔GUIDE QUESTIONS
At plasma concentrations of glucose higher than occur at transport
maximum (Tm), the
(A) clearance of glucose is zero
Filtered Load = GFR x [plasma glucose concentration] (B) excretion rate of glucose equals the filtration rate of glucose
(C) reabsorption rate of glucose equals the filtration rate of glucose
= 120 mL/min x 400 mg/dL
(D) excretion rate of glucose increases with increasing plasma
= 480 mg/min glucose concentrations
Excretion rate = V x [urine glucose concentration] (E) renal vein glucose concentration equals the renal artery glucose
= 4 mL/min x 2500 mg/dL concentration From Physiology BRS, 6 Ed th

= 100 mg/min There’s no saturation for filtration and excretion of glucose. The higher
Reabsorption rate = Filtered Load – Excretion rate the plasma concentration, the higher the glucose filtered and excreted
= 480 mg/min – 100 mg/min Dr. Banzuela

= 380 mg/min
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✔GUIDE QUESTIONS • Lowest Clearance: Protein, Na, Glucose, amino Acids, HCO3- and Cl-
At plasma para-aminohippuric acid (PAH) concentrations below the o Reason: Not filtered (protein), or filtered but mostly reabsorbed
transport maximum (Tm), PAH (everything else listed above)
(A) reabsorption is not saturated o Normally not found or found in small amounts in the urine
(B) clearance equals inulin clearance
• Clearance equal to GFR: inulin, creatinine
(C) secretion rate equals PAH excretion rate
(D) concentration in the renal vein is close to zero o Reason: filtered but not secreted not reabsorbed
(E) concentration in the renal vein equals PAH concentration in the renal § more concentrated at the end of PCT that at the start of PCT:
artery Creatinine
From Physiology BRS, 6th Ed
o Marker for Kidney function (glomerular marker)
PAH is supposed to be highly excreted since it is filtered, secreted and not o Crea Clearance = Crea excreted/plasma crea concentration
reabsorbed. Since PAH concentration is still below Tm, it means we have
✔GUIDE QUESTIONS
not fully saturated the nephrons – PAH is still being excreted. Since it is still
being excreted, little PAH can be found in the renal vein – almost all PAH Which of the following substances has the highest renal clearance?
goes to the urine. Message me if you’re having a hard time with this one. (A) Para-aminohippuric acid(PAH) (D) Na+
Dr. Banzuela (B) Inulin (E) Cl–
From Physiology BRS, 6 Ed
NONIONIC DIFFUSION (C) Glucose th

WEAK ACIDS WEAK BASES The following information was obtained in a 20-year-old college student
who was participating in a research study in the Clinical Research Unit:
HA Form (lipid-soluble) BH+ Form (water-
Plasma: [Inulin] = 1 mg/mL [X] = 2 mg/mL
Forms and A- Form (water- soluble) and B Form Urine: [Inulin] = 150 mg/mL [X] = 100 mg/mL
soluble) (lipid-soluble) Urine flow rate = 1 mL/min
• BH+ Form Assuming that X is freely filtered, which of the following statements is
predominates, less most correct?
• HA Form (A) There is net secretion of X
“back diffusion”,
predominates: more (B) There is net reabsorption of X
In Acidic • increased excretion of
“back-diffusion”, (C) There is both reabsorption and secretion of X
Urine pH weak base (e.g.,
• decreased excretion (D) The clearance of X could be used to measure the glomerular
Morphine excretion filtration rate (GFR)
of weak acids
increased by (E) The clearance of X is greater than the clearance of inulin
acidifying urine) From Physiology BRS, 6th Ed
Cinulin = UinulinV/Pinulin
• A-
Form
Cinulin = (150mg/dL)(1mL/min)/(1mg/mL)
predominates: less
• B form predominates, Cinulin = 150mL/min
back-diffusion,
In more “back- Cx = UxV/Px
• increased excretion
Alkaline diffusion”, Cx = (100mg/mL) (1mL/min)/(2mg/ml)
of weak acids (e.g.,
Urine pH • decreased excretion Cx = 50mL/min
ASA excretion
of weak bases Cx < Cinulin
increased by
Cx < GFR since Cinulin is used to estimate GFR
alkalinizing urine) X is therefore a substance that undergoes net reabsorption.
Here’s a mnemonic – “do the opposite” rule: if you overdose with an ACIDIC Side Note: if X here is greater than GFR, there is net secretion. If X = GFR,
drug (e.g., ASA), ALKALINIZE the urine so that the weak acid will be in its then X is either inulin or creatinine.
water-soluble (charged) form. If you overdose with an ALKALINE/BASIC Dr. Banzuela
drug (e.g., morphine), ACIDIFY the urine so that the weak base will once
again be in its water-soluble (charged) form).
Remember: Aspirin IRREVERSIBLY inhibits COX-1.
RENAL BLOOD FLOW (RBF)
Autosomal recessive metabolic disorder of lysine, hydroxylysine, and • Right vs. Left Renal Artery:
tryptophan metabolism:Glutaric Aciduria Type I (GA-I) Right Renal • Longer than left renal artery
Dr. Banzuela
Artery • Runs an inferior course posterior to the IVC
✔GUIDE QUESTION • Slightly higher origin compared to right
A person who takes an aspirin (salicylic acid) overdose is treated in the Left Renal renal artery
emergency room. The treatment produces a change in urine pH that
increases the excretion of salicylic acid. What was the change in urine pH,
Artery • Runs more horizontally, posterior to the left
and what is the mechanism of increased salicylic acid excretion? renal vein
(A) Acidification, which converts salicylic acid to its HA form • Renal Blood flow: 25% of Cardiac Output
(B) Alkalinization, which converts salicylic acid to its A– form o RBF is directly proportional to pressure difference between
(C) Acidification, which converts salicylic acid to its A– form
(D) Alkalinization, which converts salicylic acid to its HA form
renal artery and renal vein; inversely proportional to resistance
of renal vasculature
Listen to this audio recording while reading the section on clearance: o Vasodilation of Renal Arterioles: Increases RBF
§ e.g., PGE2, PGI2, bradykinin, NO, dopamine
CLEARANCE Nooks and crannies. Remember: bradykinin causes renal vasodilation..
Dr. Banzuela
https://qrs.ly/bbebjep
o Vasoconstriction of Renal Arterioles: Decreases RBF
§ e.g., Sympathetic NS and Angiotensin II (preferentially
Dr. Banzuela constricts efferent arterioles)
§ ANP: vasodilates Afferent Arterioles and to a lesser extent
CLEARANCE vasoconstricts Efferent Arterioles. Net effect: increases RBF
• Volume of plasma cleared of a substance per unit of time (in • Renal Plasma Flow (RPF)
mL/min or mL/24 hour) o Estimated by PAH Clearance
o Remember: You “clear” the blood to make it go to the urine o Take note: PAH Clearance underestimates true RPF by 10%
due to RPF to kidney regions that do not filter and secrete PAH
o Normal value (from Guyton): 625mL/min (other normal
values: GFR=125mL/min, tubular reabsorption=124mL/min,
urine flow rate = 1mL/min)
• Renal Blood Flow

• If substance has high clearance: most will be found in the urine


• If substance has low clearance: most will be found in the blood
• Relative Clearances:
o PAH > K > inulin > urea > Na > glucose, amino acids and HCO3- Remember the formula above. RPF is the numerator.(1-Hct) is the
• Highest Clearance: PAH denominator.
Dr. Banzuela
o Reason: Filtered and Secreted, not reabsorbed
o Used to estimate for Renal Blood Flow (RBF) and Renal Plasma
Flow (RPF)
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TOPNOTCH MEDICAL BOARD PREP PHYSIOLOGY MAIN HANDOUT BY DR. ENRICO PAOLO C. BANZUELA
For inquiries visit www.topnotchboardprep.com.ph or https://www.facebook.com/topnotchmedicalboardprep/
This handout is only valid for October 2023 PLE batch. This will be rendered obsolete for the next batch since we update our handouts regularly.
✔GUIDE QUESTIONS STARLING
DESCRIPTION
A patient is infused with para-aminohippuric acid (PAH) to measure FORCE
renal blood flow (RBF). She has a urine flow rate of 1 mL/min, a plasma • “Usually ignored”.
[PAH] of 1 mg/mL, a urine [PAH] of 600 mg/mL, and a hematocrit of BS Oncotic
45%. What is her “effective” RBF? Pressure • Normal value: 0 (no protein is normally
(A) 600 mL/min (C) 1091 mL/min filtered to BS)
(B) 660 mL/min (D) 1333 mL/min • Not a Starling Force.
From Physiology BRS, 6th Ed
• Hydraulic conductance / filtration
CPAH = UPAH × V/PPAH = 600 mL/min coefficient describes capillary
CPAH = RPF since clearance of PAH is used to estimate RPF Kf
permeability.
RBF = RPF/ (1 – hematocrit) • Promotes GFR. Increased by histamine
RBF = (6000mL/min)/ (1-0.45)
RBF = 600mL/min/0.55 • (e.g., in burns)
RBF = 1091 mL/min ✔GUIDE QUESTION
Dr. Banzuela
Glomerular capillary hydrostatic pressure = 47mmHg
Bowman’s space hydrostatic pressure = 10mmHg
GLOMERULAR FILTRATION RATE (GFR) Bowman’s space oncotic pressure = 0 mm Hg
• Amount filtered in the glomerular capillaries per unit time At what value of glomerular capillary oncotic pressure would
glomerular filtration stop?
o Normal Value: 125mL/min or 180L/day
(A) 57 mm Hg (D) 10 mm Hg
o Determined by Starling Forces at the level of the glomerular (B) 47 mm Hg (E) 0 mm Hg
capillary (glomerulus) (C) 37 mm Hg From Physiology BRS, 6 th Ed

• GFR males vs. females: 20% higher in males (but varies


Listen to the audio recording below while reading the following section
depending on the reference book) about GFR, RPF and FF:
• BUN and Creatinine increase when GFR decreases
o In pre-renal azotemia (e.g., Hypovolemia), BUN increases
more than creatinine and BUN/Crea ratio > 20:1 GFR, RPF and FF
o GFR decreases with age, but Creatinine remains constant due to https://qrs.ly/ezebjg7
decreased muscle mass
Watch the video on Starling Forces and GFR while reading the relevant Dr. Banzuela
portions below: FILTRATION FRACTION (FF)
• Fraction of renal plasma flow that is filtered
• Normal Filtration Fraction: 20%
STARLING FORCES AND GFR
o ↑ Filtration Fraction → ↑ peritubular capillary protein
https://qrs.ly/6qebjg2
concentration → ↑ reabsorption in the tubules

Dr. Banzuela
STARLING FORCES
• Describes fluid movement into (absorption) or out of GFR, RPF, FF
(filtration) the capillary EFFECT EFFECT EFFECT
ON GFR OF RPF ON FF
Vasoconstriction of
↓ ↓ No Change
Afferent Arteriole
Vasoconstriction of
↑ ↓ ↑
Efferent Arteriole
↑ Plasma Protein ↓ No Change ↓
Ureteral Stone ↓ No Change ↓
• Compression of the renal capsule will cause: decreased GFR
✔GUIDE QUESTIONS
© Topnotch Medical Board Prep
Which of the following would produce an increase in the reabsorption of
• Favors increase in GFR: Increased glomerular capillary (GC) isosmotic fluid in the proximal tubule?
hydrostatic pressure, Decreased GC oncotic Pressure, Decreased (A) Increased filtration fraction
Bowman Space (BS) hydrostatic pressure, Increase Filtration (B) Extracellular fluid (ECF) volume expansion
Coefficient (KF) (C) Decreased peritubular capillary protein concentration
(D) Increased peritubular capillary hydrostatic pressure
GLOMERULAR FILTRATION RATE (E) Oxygen deprivation From Physiology BRS, 6 Ed
th

Which of the following would cause an increase in both glomerular


• GFR = Kf [(PGC-PBS) – (OGC- OBS)] filtration rate (GFR) and renal plasma flow (RPF)?
o Kf = Filtration coefficient of the Glomerular Capillaries (A) Hyperproteinemia (D) Dilation of the efferent arteriole
o PGC= Glomerular Capillary Hydrostatic Pressure (B) A ureteral stone (E) Constriction of the efferent arteriole
o PBS = Bowman’s Space Hydrostatic Pressure (C) Dilation of the afferent arteriole From Physiology BRS, 6 Ed
th

o OGC= Glomerular Capillary Oncotic Pressure (mmHg) AUTOREGULATION OF RENAL BLOOD FLOW
o OBS = Bowman’s Space Oncotic Pressure (mmHg)
• helps maintain constant GFR
o Occurs at BP 80-200mmHg (in other textbooks: at BP 75-
NOTES ON GLOMERULAR CAPILLARY STARLING FORCES
160mmHg), renal blood flow remains constant via
STARLING § Myogenic mechanism
DESCRIPTION
FORCE - renal afferent arterioles reflexively responds to stretch
• ” Water pressure” at the GC. by contracting in order to maintain constant renal blood
• Promotes GFR. flow and subsequently, GFR
GC Hydrostatic
• Increased by vasodilation of afferent § Tubuloglomerular Feedback / Macula Densa Feedback
Pressure
arteriole or moderate vasoconstriction of - Remember: this is not the same as glomerulotubular balance
efferent arteriole
Scenario 1: if BP is low (e.g., 80mmHg)
• “Water pressure” at the BS that opposes GC
• ↓ BP → ↓ GC Hydrostatic Pressure → ↓ GFR (<125ml/min) →
hydrostatic Pressure and GFR.
BS Hydrostatic Detected by Macula Densa
• Also called “Bowman Capsule Pressure”
Pressure • Macula Densa increases secretion of:
• Increased by ureteral obstruction (e.g., o Angiotensin II (via RAAS stimulation)
kidney stone) § Vasoconstricts EFFERENT Arteriole → ↑ GFR back to normal
• “Proteins attracting water” at the GC. (125ml/min)
GC Oncotic • Opposes GFR. o Nitric Oxide
Pressure • Increased by plasma protein § Vasodilates AFFERENT Arteriole → ↑ GFR back to normal
concentration. (125ml/min)
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TOPNOTCH MEDICAL BOARD PREP PHYSIOLOGY MAIN HANDOUT BY DR. ENRICO PAOLO C. BANZUELA
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This handout is only valid for October 2023 PLE batch. This will be rendered obsolete for the next batch since we update our handouts regularly.
Scenario 2: if BP is high (e.g., 200mmHg) CAUSES OF INCREASED CAUSES OF DECREASED
• ↑ BP → ↑ GC Hydrostatic Pressure → ↑ GFR (>125ml/min) → DISTAL K SECRETION DISTAL K SECRETION
Detected by Macula Densa • High K+ diet • Low K+ Diet
• Macula Densa increases secretion of: • Hyperaldosteronism • Hypoaldosteronism
o Adenosine: Vasoconstricts AFFERENT arteriole → ↓ GFR back to • Alkalosis • Acidosis
normal (125ml/min) • Thiazide Diuretics • K+-Sparing Diuretics
§ Adenosine is normally a vasodilator, but in the kidney, it • Loop Diuretics
acts as a vasoconstrictor of the AFFERENT arteriole! • Luminal Anions
Remember that there are 3 organs that have autoregulation of blood flow
as discussed in the cardio module: brain, heart and kidney. For the kidney, Memorize also the table above.
Dr. Banzuela
the reason why they are given the power to regulate the diameter of their
arterioles (and therefore regulate their own blood flow) is to maintain a ✔GUIDE QUESTION
CONSTANT GFR. The number one suspected mechanism for renal Secretion of K+ by the distal tubule will be decreased by
autoregulation of blood flow is Tubuloglomerular feedback/macula densa (A) metabolic alkalosis (D) spironolactone
feedback. Take note of the substances produced to dilate/constrict the (B) a high-K+ diet administration
afferent/efferent arterioles whenever BP is low or high (see section above). (C) hyperaldosteronism (E) thiazide diuretic administration
Dr. Banzuela From Physiology BRS, 6th Ed

REMEMBER! AUTOREGULATION OF RENAL BLOOD FLOW Remember the spironolactone is an aldosterone antagonist, it will
decrease K+ secretion to the urine, and may in fact cause hyperkalemia.
TUBULOGLOMERULAR FEEDBACK
Spironolactone has another adverse effect btw: gynecomastia.
Macula Densa Feedback; For Autoregulation of GFR Dr. Banzuela

GLOMERULOTUBULAR BALANCE
Percentage of solute reabsorbed is held constant; Buffers effect 5.4 RENAL REGULATION OF UREA, PHOSPHATE,
of drastic GFR changes on urine output CALCIUM AND MAGNESIUM
5.3 K+ REGULATION REGULATION OF UREA
• Urea: breakdown product of protein catabolism
REGULATION OF POTASSIUM
o Synonym: carbamide
• Plasma K+ = 4.2 mEq/L and tightly-regulated o accumulation of urea: Uremia
• 1st Line of defense • PCT: reabsorbs 50% of filtered Urea via simple diffusion
o Movement of K+ across ECF and ICF
• Thin Descending Limb of LH: secretes urea via simple diffusion
CAUSES OF K+ EFFLUX → CAUSES OF K+ INFLUX →
• DT, Cortical Collecting Ducts and Outer Medullary Collecting
HYPERKALEMIA HYPOKALEMIA
Ducts: Impermeable to Urea
• Insulin deficiency • Insulin • Inner Medullary Collecting Ducts: ADH increases permeability
• Beta-adrenergic antagonist • Beta-adrenergic agonists of these ducts to via facilitated diffusion transporter for urea
• Acidosis • Alkalosis (UT1)
• Hyperosmolarity • Hypoosmolarity o Contributes to urea recycling and development of
• Inhibitors of Na+-K+-ATPase corticopapillary osmotic gradient
pump like digitalis o ↑ ADH secretion → ↑ Water AND Urea reabsorption → Low Urine
• Exercise Flow Rate
• Cell Lysis Urea is important. Without urea and UT-1 transporters, maximum
Memorize the table above. Some key points: insulin causes K+ influx that’s osmolarity at the renal interstitium near the tip of the LH would only be
why it’s used in the treatment of hyperkalemia. Mechanism is unknown but 600 instead of 1200mOsm/L. Urea is a solute that increases maximum
number one suspected mechanism is to increase activity of the Na+-K+- urine osmolality (it doubles it).
ATPase pump. Acidosis causes K+ efflux, predisposing you to hyperkalemia. Dr. Banzuela

Why? Our body prioritizes acid-base balance in plasma more than anything REGULATION OF CALCIUM
else since acids/bases can kill you very fast through denaturation of • Plasma Ca2+ = 2.4mEq/L
proteins. So, if you have acidosis, our body compensates by moving H+ from • Hypercalcemia: can cause arrhythmias
ECF to ICF in exchange for K+ (the number one intracellular cation) moving • Hypocalcemia: can cause tetany
from ICF to ECF. Cell lysis (e.g., in tumor lysis syndrome) can cause rupture
• Calbindin: Stimulated by vit D; binds with calcium in the intestines
of cells, which will release their contents – including the intracellular K+.
Dr. Banzuela • 60% of plasma Ca2+ is filtered
✔GUIDE QUESTION • PCT and LH reabsorbs 90% of filtered Calcium
Which of the following causes hyperkalemia? • DT and CD reabsorbs 8% of filtered Calcium
(A) Exercise (D) Decreased serum osmolarity • PTH, Thiazides increases Ca Reabsorption
(B) Alkalosis (E) Treatment with β-agonists • Loop Diuretics decreases Ca Reabsorption
From Physiology BRS, 6 Ed
(C) Insulin injection th

RENAL REGULATION OF K+ BALANCE


• K+ Balance achieved when:
o Urinary excretion of K+ = K+ dietary intake
• K excretion varies from 1-110% of filtered load depending of
dietary K, aldosterone levels and acid-base status
• Principal Cells: secrete K
• Intercalated Cells: reabsorbed K (active in low K diet)

© Topnotch Medical Board Prep


REGULATION OF PHOSPHATE
• Transport Maximum = 0.1mM/min
• Often exceeded in diets with milk and meat
• PCT: reabsorbs 85% of filtered Phosphate via Na-PO4
cotransport; other parts to do not reabsorb PO4
o remaining 15% is excreted in the urine
© Topnotch Medical Board Prep o Reabsorption inhibited by PTH (adenylate cyclase and cAMP
K+ SECRETION IN THE DT USING PRINCIPAL CELLS inhibition of the Na-PO4 cotransport)
• K+ secretion by the Principals Cells in the LDT can be increased § Causes Phosphaturia (increased urinary PO4) and
or decreased by several factors. increased urinary cAMP
• This can lead to changes in plasma K+ o Unreabsorbed PO4 serve as urinary buffer for H+
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TOPNOTCH MEDICAL BOARD PREP PHYSIOLOGY MAIN HANDOUT BY DR. ENRICO PAOLO C. BANZUELA
For inquiries visit www.topnotchboardprep.com.ph or https://www.facebook.com/topnotchmedicalboardprep/
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This is board-relevant: Phosphate reabsorption occurs only in the PCT and Refer to the next table as you listen to the audio recording:
nowhere else. 85% of filtered phosphate is reabsorbed in the PCT, the
remaining 15% is not reabsorbed anywhere else, and becomes part of the
urinary buffer for excess acids. CONDITIONS INVOLVING ADH
Dr. Banzuela
https://qrs.ly/v1ebjgh
REGULATION OF MAGNESIUM
• Plasma Mg2+ = 1.8mEq/L
• 50% stored in the bones Dr. Banzuela

• Only 10% of plasma Mg excreted daily CONDITIONS INVOLVING ADH


Urine
o PCT -25% reabsorption Serum
Flow
o TAL of LH – 65% reabsorption Serum Osm/
Urine Osm Rate / CH2O
ADH Serum
§ In the TAL of LH, Ca2+ and Mg2+ compete for reabsorption Na
Urine
- Hypercalcemia causes hypomagnesemia Volume
- Hypocalcemia causes hypermagnesemia Primary
↓ ↓ Hypoosmotic ↑ (+)
Polydipsia
This is a favorite in quiz bee competitions: Magnesium is the only solute not
mainly reabsorbed in the PCT. It is mainly reabsorbed in the TAL of LH. Central DI ↓ ↑ Hypoosmotic ↑ (+)
Dr. Banzuela Peripheral
↑ ↑ Hypoosmotic ↑ (+)
DI
5.5 CONCENTRATION & DILUTION OF URINE Water

↑ TO
Hyperosmotic ↓ (-)
WATER DEPRIVATION VS. WATER INTAKE Deprivation NORMAL
WATER WATER SIADH ↑↑ ↓ Hyperosmotic ↓ (-)
DEPRIVATION INTAKE • Cause of Hyponatremia in patient with Small Cell Lung CA:
Immediate effect on Arginine Vasopressin (SIADH)
↑ ↓
Plasma Osmolarity • increased free water clearance is a hallmark of: Diabetes
Effect on Osmoreceptors Insipidus
Stimulates Inhibits
in Anterior Hypothalamus
ADH Secretion from ✔GUIDE QUESTIONS
↑ ↓
Posterior Pituitary Which of the following would best distinguish an otherwise healthy
Effect on water person with severe water deprivation from a person with the syndrome
↑ ↓ of inappropriate antidiuretic hormone (SIADH)?
permeability in DT & CD
Effect on Urine (A) Free-water clearance (CH2O)
↑ ↓ (B) Urine osmolarity
Osmolarity
Effect on Urine Volume ↓ ↑ (C) Plasma osmolarity
(D) Circulating levels of antidiuretic hormone (ADH)
↓ Plasma ↑ Plasma
Final Result on Plasma (E) Corticopapillary osmotic gradient From Physiology BRS, 6 Ed th

osmolarity back osmolarity back


Osmolarity Person with severe water deprivation will have HIGH plasma
to normal to normal osmolarity due to water loss from sweating not replaced by water
PRODUCTION OF CONCENTRATED URINE intake. Person with SIADH will have LOW plasma osmolarity due to
increased water reabsorption from the kidneys that goes to plasma.
• In the presence of ADH, filtrate will be isotonic to plasma in the: Dr. Banzuela
cortical collecting tubule A negative free-water clearance (–CH2O) will occur in a person who
• Concentrated urine / Hyperosmotic Urine: (A) drinks 2 L of distilled water in 30 minutes
o Urine osmolarity > blood osmolarity (B) begins excreting large volumes of urine with an osmolarity of 100
• Mechanisms: mOsm/L after a severe head injury
(C) is receiving lithium treatment for depression, and has polyuria
o Corticopapillary Osmotic Gradient / Graded Osmolarity in
that is unresponsive to the administration of antidiuretic
the Renal Interstitium hormone (ADH)
§ Created by Countercurrent Multiplier: Loop of Henle (D) has an oat cell carcinoma of the lung, and excretes urine with
§ Supplemented by Urea Recycling: increases maximum an osmolarity of 1000 mOsm/L From Physiology BRS, 6 Ed th

osmolarity from 600mOsm/L to 1200mOsm/L Since D is associated with SIADH which will cause a negative free-water
§ Maintained by Countercurrent Exchanger: Vasa Recta clearance due to the high levels of ADH.
o High ADH secretion Dr. Banzuela
Compared with a person who ingests 2 L of distilled water, a person with
§ inserts AQP-2 (water channels) in the LDT and CD to ↑ water water deprivation will have a
reabsorption → ↑ urine osmolarity and ↓ urine volume (A) higher free-water clearance (CH2O)
§ Inserts UT1 to ↑ Urea recycling and ↑ NaK2Cl activity in TAL (B) lower plasma osmolarity
LH to ↑ osmolarity of the corticopapillary osmotic gradient (C) lower circulating level of antidiuretic hormone (ADH)
PRODUCTION OF DILUTE URINE (D) higher tubular fluid/plasma (TF/P) osmolarity in the proximal
• Dilute urine / Hypoosmotic Urine: tubule
o Urine osmolarity < blood osmolarity (E) higher rate of H2O reabsorption in the collecting ducts
From Physiology BRS, 6th Ed
• ADH levels are low or ineffective A person with water deprivation will have a higher plasma osmolarity
o Less countercurrent multiplication, urea recycling and insertion due to sweating not replaced with water intake. ADH secretion will
of AQP-2 ensue due to increased plasma osmolarity. ADH will then cause increase
• Urine: high volume, low concentration water reabsorption in the CD.
Dr. Banzuela

FREE WATER CLEARANCE (CH2O) A woman has a plasma osmolarity of 300 mOsm/L and a urine osmolarity
• Free Water (Solute Free Water) of 1200 mOsm/L. The correct diagnosis is
(A) syndrome of inappropriate antidiuretic hormone (SIADH)
o Produced by diluting segments of the kidney (TAL LH and EDT)
(B) water deprivation
where NaCl is reabsorbed but not water (C) central diabetes insipidus
• Free Water Clearance (CH20) (D) nephrogenic diabetes insipidus
o Estimates ability to concentrate or dilute the urine (E) drinking large volumes of distilled water
§ If (-) ADH: Free Water excreted and CH2O is positive From Physiology BRS, 6th Ed

§ If (+) ADH: Free Water is NOT excreted (water is Patient here has normal plasma osmolarity but high normal urine
reabsorbed) and CH20 is negative osmolarity. If you are deprived of water (while sweating is still going
on), you would lose water more than salt via sweating. This would
increase the plasma osmolarity. ADH will be secreted as a response to
normalize plasma osmolarity. However, that ADH would cause
increased urine osmolarity and decreased urine volume due to
increased water reabsorption from the kidneys.
This is NOT SIADH – SIADH would cause an increase in urine osmolarity,
Again: Free water clearance → if positive (or high), free water is going to but it would also cause a DECREASE in plasma osmolarity (plasma
your urine (it is excreted); this happens when there is no ADH. If you have osmolarity < 300mOsm/L)
ADH, free water is reabsorbed and free water clearance is negative (or low). Condition that presents with hypernatremia, polyuria, low urine Na,
Wag mapagbabaligtad ang positive and negative free water clearance. hypoosmolar urine: Diabetes Insipidus
Dr. Banzuela

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TOPNOTCH MEDICAL BOARD PREP PHYSIOLOGY MAIN HANDOUT BY DR. ENRICO PAOLO C. BANZUELA
For inquiries visit www.topnotchboardprep.com.ph or https://www.facebook.com/topnotchmedicalboardprep/
This handout is only valid for October 2023 PLE batch. This will be rendered obsolete for the next batch since we update our handouts regularly.
RENAL HORMONES RESPIRATORY REGULATION OF ACID-BASE BALANCE
HORMONE SITE OF ACTION EFFECTS • Responds to H+ levels
↑ Na+ and H2O o ↑ H+ → ↑ RR → ↓ plasma PCO2
reabsorption o ↓ H+ → ↓ RR → ↑plasma PCO2
Aldosterone DT • 50-75% effective in returning pH back to normal within 3-12
↑ K+ secretion
↑ H+ Secretion minutes
↑ Na+ reabsorption
↑ H2O reabsorption RENAL REGULATION OF ACID-BASE BALANCE
Angiotensin II PCT, TAL, LH, DT ↑ Na+-H+ antiport and • Mechanisms:
HCO3- reabsorption o Secretion of excess H+
in the PCT § Na+-H+ Countertransport in the PCT , LH, DT
PCT, TAL LH, DT, ↑ Water, Na+ § H+ATPase pump in the Distal Tubules and CD
Catecholamines o Reabsorption of filtered HCO3- if warranted
CD reabsorption
ANP, B-Type DT, CD (MOA: § Coupled to H+ Secretion
Natriuretic guanylate cyclase, ↓ Na+ reabsorption o Production of New HCO3- if warranted
Peptide or BNP cGMP) § Use of Ammonia (NH3) and Phosphate (NaHPO4-) buffers
Uroguanylin, ↓ Water, Na+ - These buffers also help excrete titratable acids
PCT, CD
Guanylin reabsorption
↓ Water, Na+
Dopamine PCT
reabsorption
↓ phosphate
reabsorption
PCT, TAL LH
↑ Ca2+ reabsorption
PTH (MOA: Adenylate
Stimulates 1-alpha
cyclase, cAMP)
hydroxylase for Vit D
final activation
TAL LH, LDT, CD
↑ water permeability,
(MOA: V2 receptor,
ADH ↑reabsorption and
adenylate cyclase,
Na-K-2Cl activity
cAMP)
Released by Ventricular myocytes due to increased tension: B-Type
Natriuretic Peptide (BNP or Brain Natriuretic Peptide)
Dr. Banzuela © Topnotch Medical Board Prep

• Formula for Net Acid Excretion:


5.6 ACID-BASE BALANCE
BASIC ACID-BASE PHYSIOLOGY o NAE: Net acid excretion
• Almost all enzyme systems are influenced by H+ levels and must o V: Volume of urine produced per unit time
be regulated o UNH4: Urine concentration of ammonium
o Normal Plasma H+ = 0.00004 mEq/L o UTA: Urine concentration of titratable acid
§ Cumbersome! o UHCO3: Urine concentration of bicarbonate
§ Reason for using pH system
o Normal Plasma pH = -log [H+] = 7.4 ✔GUIDE QUESTION
The reabsorption of filtered HCO3–
• pH = 6.8 – 8.0
(A) results in reabsorption of less than 50% of the filtered load when
o Compatible with life the plasma concentration of HCO3– is 24 mEq/L
(B) acidifies tubular fluid to a pH of 4.4
H+ Concentration (mEq/L) pH (C) is directly linked to excretion of H+ as NH4+
Extracellular fluid (D) is inhibited by decreases in arterial PCO2
Arterial blood 4.0 x 10-5 7.40 (E) can proceed normally in the presence of a renal carbonic
anhydrase inhibitor From Physiology BRS, 6 Ed
Venous blood 4.5 x 10-5 7.35
th

Interstitial fluid 4.5 x 10-5 7.35 Listen to this audio recording while reading the section below on acid-
Intracellular fluid 1 x 10-3 to 4 x 10-5 6.0-7.4 based abnormalities:
Urine 3 x 10-2 to 1 x 10-5 4.5-8.0
Gastric HCI 160 0.8 ACID-BASE ABNORMALITIES
Adapted from Table 31-1. Hall JE. Guyton and Hall Textbook of Medical Physiology. 13th ed. 2016
Look at the table above from Guyton. Gastric HCl has a pH of 0.8 (in review https://qrs.ly/vqebjgj
books, they round this off to 1-3.5). pH can indeed be less than 1 (it can even
be a negative number) or be more than 14; it’s just difficult to measure Dr. Banzuela
those values that’s why pH scale is written usually as 0-14 or 1-14.
Dr. Banzuela

✔GUIDE QUESTION ACID-BASE ABNORMALITIES


To maintain normal H+ balance, total daily excretion of H+ should equal pH H+ PCO2 HCO3- COMPENSATION
the daily 40 40 24
Normal 7.4 --
(A) fixed acid production plus fixed acid ingestion mEq/L mmHg mEq/L
(B) HCO3– excretion • ↑ Excretion
H+
Respiratory
(C) HCO3– filtered load ↓ ↑ ↑↑ ↑ • ↑HCO3-
Acidosis
(D) titratable acid excretion Reabsorption
(E) filtered load of H+ From Physiology BRS, 6th Ed • ↓ H+ Excretion
Respiratory
BASIC ACID-BASE PHYSIOLOGY ↑ ↓ ↓↓ ↓ • ↓ HCO3-
Alkalosis
Reabsorption
• Systems that regulate H+ Concentrations
Metabolic
o Body Fluid Buffer Systems ↓ ↑ ↓ ↓↓ • Hyperventilation
Acidosis
§ CO2 + H2O ↔ H2CO3 ↔ H+ + HCO3-
Metabolic
§ Phosphate Buffer System (H2PO4- and HPO4-) ↑ ↓ ↑ ↑↑ • Hypoventilation
Alkalosis
§ Intracellular Proteins
o Respiratory Center REMEMBER TRIO OF ELECTROLYTES
§ Controls PCO2 (Respiratory Acidosis/Alkalosis) H+, Ca++, K+
o Kidneys áH+ levels à HyperCalcemia
§ Controls HCO3- (Metabolic Acidosis/Alkalosis) HyperKalemia
• Most of the volatile acid entering the blood is buffered by:
Hemoglobin
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RESPIRATORY ACIDOSIS ✔GUIDE QUESTIONS
• Due to conditions resulting in Decreased Ventilation (RR) A 45-year-old woman develops severe diarrhea while on vacation. She
has the following arterial blood values:
• e.g., Opiates, Sedatives, Anesthetics, Guillain-Barré Syndrome,
pH = 7.25
Polio, Amyotrophic Lateral Sclerosis, Multiple Sclerosis, Airway PCO2 = 24 mm Hg
Obstruction, ARDS, COPD [HCO3–] = 10 mEq/L
• MOA of motor paralysis in GBS: demyelination of Type A-Beta Venous blood samples show decreased blood [K+] and a normal anion
Fibers gap. The correct diagnosis for this patient is
(A) metabolic acidosis (D) respiratory alkalosis
RESPIRATORY ALKALOSIS
(B) metabolic alkalosis (E) normal acid–base status
• Due to conditions resulting in Increased Ventilation (RR) (C) respiratory acidosis From Physiology BRS, 6 Edth

• e.g., Pneumonia, Pulmonary embolus, High Altitude, Psychogenic, A 45-year-old woman develops severe diarrhea while on vacation. She
Salicylate Intoxication has the following arterial blood values:
pH = 7.25
METABOLIC ACIDOSIS PcO2 = 24 mm Hg
• Due to conditions resulting in excess acid or loss of base [HCO3–] = 10 mEq/L
• e.g., Ketoacidosis, Lactic Acidosis, Salicylate Intoxication, Venous blood samples show decreased blood [K+] and a normal anion
Methanol/ Formaldehyde Intoxication, Ethylene glycol gap. Which of the following statements about this patient is correct?
intoxication, Diarrhea (A) She is hypoventilating
(B) The decreased arterial [HCO3–] is a result of buffering of excess H+
• Anion Gap (AG) used to help diagnose cause of metabolic acidosis
by HCO3–
(C) The decreased blood [K+] is a result of exchange of intracellular H+
for extracellular K+
(D) The decreased blood [K+] is a result of increased circulating
levels of aldosterone
(E) The decreased blood [K+] is a result of decreased circulating levels
of antidiuretic hormone (ADH) From Physiology BRS, 6 Ed
th

Remember: A patient has the following arterial blood values:


ECF: major cation: Na+. major pH = 7.52
anions: Cl- and HCO3-. PCO2 = 20 mm Hg
ICF: major cation: K+. major [HCO3–] = 16 mEq/L
anions: proteins, ATP, ADP Which of the following statements about this patient is most likely to be
Dr. Banzuela
correct?
(A) He is hypoventilating
(B) He has decreased ionized [Ca2+] in blood
(C) He has almost complete respiratory compensation
(D) He has an acid–base disorder caused by overproduction of fixed
acid
© Topnotch Medical Board Prep
(E) Appropriate renal compensation would cause his arterial
[HCO3–] to increase From Physiology BRS, 6 Edth

Remember trio of electrolytes mnemonic? Alkalosis will cause


decreased plasma Ca2+
Dr. Banzuela
A patient arrives at the emergency room with low arterial pressure,
reduced tissue turgor, and the following arterial blood values:
pH = 7.69
• High-anion gap metabolic acidosis (HAGMA) [HCO3–] = 57 mEq/L
o Decreased HCO3- PCO2 = 48 mm Hg
o ↑ Organic Anions (e.g. ketoacids, salicylate) to maintain Which of the following responses would also be expected to occur in this
electroneutrality patient?
• Normal-anion gap metabolic acidosis (NAGMA) (A) Hyperventilation
o Decreased HCO3- (B) Decreased K+ secretion by the distal tubules
(C) Increased ratio of H2PO4– to HPO4–2 in urine
o ↑ Chloride to maintain electroneutrality (D) Exchange of intracellular H+ for extra-cellular K+
o Also called Hyperchloremic Metabolic Acidosis with Normal From Physiology BRS, 6th Ed
Anion Gap
MNEMONICS METABOLIC ACIDOSIS 5.7 INTEGRATIVE EXAMPLES
MUDPILES: HAGMA ADDISON DISEASE
Methanol, Uremia, DKA, Paraldehyde, Propylene Glycol, Iron • ↓adrenocortical hormones – aldosterone, cortisol and weak
Isoniazid, Idiopathic Acidosis, Lactic Acidosis (in Sepsis, Shock), androgens
Ethylene Glycol, Ethanol, Salicylic Acid • ↓ aldosterone results in:
HARD-UP: NAGMA o ↓ Na and H2O reabsorption:
Hyperalimentation, Acetazolamide, RTA, Diarrhea, § ↓ IVV → ↓ VR → ↓ CO → ↓ BP → stimulates BRR → ↑HR
Ureteroenteric fistula, Pancreaticoduodenal Fistula § ECF Volume Contraction → ↑ inappropriate ADH secretion →
hypoNa
Memorize MUDPILES and HARD-UP mnemonic. Very useful shortcuts
whenever you have cases in the exams dealing with ABG interpretation. o ↓ K secretion: Hyperkalemia
o ↓ H secretion: Metabolic acidosis
Acetazolamide: drug used in the treatment of acute mountain sickness.
It is a Carbonic Anhydrase Inhibitor (CAI) and the one associated with ✔GUIDE QUESTION
metabolic ACIDOSIS (mnemonic: ACIDazolamide) A man presents with hypertension and hypokalemia. Measurement of his
Don’t forget: NAGMA is associated with INCREASED CHLORIDE. HAGMA arterial blood gases reveals a pH of 7.5 and a calculated HCO3– of 32
with INCREASED ORGANIC ANIONS. mEq/L. His serum cortisol and urinary vanillylmandelic acid (VMA) are
Dr. Banzuela normal, his serum aldosterone is increased, and his plasma renin activity
METABOLIC ALKALOSIS is decreased. Which of the following is the most likely cause of his
hypertension?
• Due to conditions resulting in loss of acid or gain of base
(A) Cushing syndrome (D) Renal artery stenosis
• e.g., Loop Diuretics, Thiazide Diuretics, Vomiting, Hyperaldosteronism, (B) Cushing disease (E) Pheochromocytoma
Ingestion of Alkaline Drugs (Sodium Bicarbonate) (C) Conn syndrome From Physiology BRS, 6 Ed th

✔GUIDE QUESTIONS HPN can have the following lethal effects: heart attack, heart failure, stroke
Which of the following is a cause of metabolic alkalosis? (cerebral blood vessels rupture or clog more easily), kidney failure, vision
(A) Diarrhea (D) Treatment with acetazolamide loss, sexual dysfunction, angina, peripheral artery disease. .
(B) Chronic renal failure (E) Hyperaldosteronism Dr. Banzuela

(C) Ethylene glycol ingestion From Physiology BRS, 6 Ed th


VOMITING
Since aldosterone cause H+ secretion to the urine, hyperaldosteronism • Loss of HCl from stomach:
(e.g., Conn syndrome) will cause metabolic alkalosis. o Metabolic alkalosis, hypochloremia and ECF Volume
Dr. Banzuela Contraction
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• ECF Volume Contraction:
o ↓ Renal Perfusion Pressure → ↑ Angiotensin II and Aldosterone
• ↑ Angiotensin II:
o ↑ Na+-H+ exchange, ↑ HCO3- reabsorption → Metabolic Alkalosis
• ↑ Aldosterone:
o ↑ H+ secretion → Metabolic Alkalosis
o ↑ K+ secretion → Hypokalemia

DIARRHEA
• Loss of HCO3-
o Metabolic Acidosis
• Respiratory Compensation: Hyperventilation
• ECF Volume Contraction:
o Stimulates BRR → ↑ HR © Topnotch Medical Board Prep

o Stimulates RAAS → hypokalemia Wag deadmahin ang muscularis mucosa. This muscularis mucosa is the
smooth muscle responsible for GI secretions. It is innervated by the
• most likely seen in osmotic diarrhea: increase in the stool
Meissner plexus. The circular and longitudinal muscles are the ones
osmotic gap (>50mOsm) innervated by the Auerbach plexus for motility.
Functions of Peyer Patches: Immune surveillance
PRE-TEST EQUATIONS Contains macrophages (that phagocytizes bacteria), B-cells and T-cells
FRACTIONAL EXCRETION OF NA Contains M cells that act as “antigen-DELIVERY” cells
Example of cross-over question: mechanism of Salmonella typhi in invading
the ileum? A: M cells in the intestine. This question is more appropriate
for the other med boards subjects
• Question Dr. Banzuela

o 38/F decreased urine output. (+) ibuprofen use. INNERVATION OF THE GI TRACT
o Labs: • Extrinsic
§ BUN: 49mg/dL o Parasympathetic (Excitatory)
§ Serum Na = 135 mmol/L • From pharynx to proximal 2/3 of transverse colon
§ Serum creatinine: 7.5mg/dL Vagus
• Vagovagal reflexes: Reflexes in which both afferent
§ Urine Na = 33 mmol/L Nerve
& efferent pathways are contained in Vagus nerve
§ Urine creatinine = 90mg/dL Pelvic • Innervates from distal 1/3 of transverse colon to
What is her fractional Na excretion? Nerve upper portion of anal canal
• Answer o Sympathetic (Inhibitory)
o Fractional Excretion (FE) • Intrinsic (Enteric Nervous System): Coordinates and relays
- ×/
o FE = amount excreted/amount filtered = !" info from ANS to GI tract
0!" ×123
o 𝐺𝐹𝑅 =
-#$%" ×/ MEISSNER PLEXUS AUERBACH PLEXUS
0#$%" SYNONYM Submucosal Plexus Myenteric Plexus
-!" ×/ -!" ×0#$%"
o 𝐹𝐸 = &#$%" ×( = between inner
0!" × 0!" ×-#$%" between submucosa
)#$%"
circular and outer
4456×7.95:/<=
= >4956×?@5:/<= = 0.02 LOCATION and inner circular
o longitudinal muscle
muscle layer
§ FE<1%: volume depletion layer
§ FE>2%: acute renal failure inner circular and
MUSCLE(S)
Muscularis Mucosa outer longitudinal
INNERVATED
muscles
6. GASTROINTESTINAL PHYSIOLOGY ACTION Secretion Motility
1. Structure and Innervation of the GIT
2. Regulatory Substances in the GIT The differences between Meissner Plexus and Auerbach Plexus are favorites in any
3. GI Motility physiology exam. Know them by heart – their synonyms, location and actions.
4. GI Secretion Remember the most basic: Meissner for Secretions, Auerbach for Motility.
Dr. Banzuela
5. Digestion and Absorption
SPECIAL NOTES ON THE LAYERS OF THE GIT
6. Liver Physiology
• Layer not seen in Esophagus: Serosa
The GI tract is just one long tube from mouth to anus. For an intro to the
GIT, watch this video:
• Strongest Layer of the esophagus: Submucosa
• 3 Muscle Layers of the Stomach: Inner Oblique, Middle Circular,
Outer Longitudinal
INTRO TO THE GIT • Myenteric Plexus is mainly excitatory EXCEPT for: Pyloric
https://qrs.ly/33ebjgw Sphincter (PS), Ileocecal Valve (ICV)

6.2 REGULATORY SUBSTANCES IN THE GIT


Dr. Banzuela
Hormones are chemical messengers released into the blood and acts on
distant sites. There are 5 OFFICIAL GI hormones and several CANDIDATE
6.1 STRUCTURE & INNERVATION OF THE GIT GI hormones (not officially accepted). Paracrines are substances released
LAYERS OF THE GIT to act on NEARBY cells (“para” means “near”). Neurocrines are substances
that induce action potentials. Take note of the definitions of hormones,
• Mucosa paracrines and neurocrines.
o Epithelium: for secretion and absorption Dr. Banzuela

o Lamina Propria: contains connective tissue, blood vessels and


lymphoid structures (Peyer patches)
o Muscularis Mucosa: smooth muscle controlling epithelium
• Submucosa
o Collagen, elastin, glands, blood vessels
• Muscularis externa
o Inner Circular: decreases diameter of lumen
o Outer Longitudinal: shortens segment of GIT
• Serosa
o a.k.a. adventitia / mesothelium

© Topnotch Medical Board Prep

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TOPNOTCH MEDICAL BOARD PREP PHYSIOLOGY MAIN HANDOUT BY DR. ENRICO PAOLO C. BANZUELA
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This handout is only valid for October 2023 PLE batch. This will be rendered obsolete for the next batch since we update our handouts regularly.

THE 5 OFFICIAL GI HORMONES


GI HORMONE STIMULI SOURCE ACTIONS
• Proteins and amino acids
(especially the amino
acids phenylalanine (F),
tryptophan (W) and G cells of the GASTRIC
• Stimulates parietal cells in oxyntic glands in the
methionine (M), Gastric ANTRUM (not in the cardia-
GASTRIN body and fundus of stomach for HCl secretion,
Distention fundus area!), duodenum,
growth of gastric mucosa
• Other triggers: gastric jejunum
distention,
parasympathetic nervous
system
• Bile secretion: Gallbladder contraction,
Sphincter of Oddi relaxation
• Main trigger: fatty acids • Decreases gastric emptying / increases gastric
• Other triggers: small I cells in the duodenum, emptying time
CCK
peptides, amino acids, jejunum ileum • Stimulates pancreatic enzyme secretion
monoglycerides • Potentiates secretin-induced stimulation of
pancreatic HCO3- secretion
• Inhibits H+ secretion of the parietal cells
• Stimulates pancreatic HCO3- secretion and
exocrine pancreatic growth
• H+ in the duodenum
• Inhibits H+ secretion of the parietal cells
(when intestinal luminal S cells in the duodenum,
SECRETIN • Stimulates HCO3- and H2O secretion by the liver
pH<4.5) jejunum and ileum
• Increases bile production
• fatty acids in duodenum
• this hormone does NOT affect pancreatic
ENZYME secretion
GLUCOSE-
• mainly by Oral Glucose • Stimulates insulin secretion
DEPENDENT K cells in the duodenum and
• others: fatty acids, amino • Above normal physiologic levels, inhibits gastric
INSULINOTROPIC jejunum
acids emptying
PEPTIDE (GIP)
• Activates interdigestive / migrating
myoelectric complex (MMC)
M cells in the duodenum and
MOTILIN • Fasting • Acts only on the stomach and small intestines
Jejunum
by stimulating their motility (has no effect on the
large intestines)
Another favorite in the med boards. Remember the characteristics of the 5 official GI hormones listed above. Remember everything listed in the table above. To
help you – when you see gastrin, think of HCl. When you see secretin, think of anti-HCl actions. Note: both H+ and fatty acids stimulate secretin release. When
you see CCK, think of fat, bile secretion and decreased gastric emptying. When you see GIP, think increased insulin as a result of oral (not IV) glucose. And
when you see motilin, think of fasting and increased GI motility to remove remnant food in the GI tract.
Dr. Banzuela

✔GUIDE QUESTIONS • Glucagon-Like Peptide 1 (GLP-1)


Cholecystokinin (CCK) has some gastrin-like properties because both o Secreted by L-cells of small intestines
CCK and gastrin o Stimulates insulin secretion
(A) are released from G cells in the stomach o Maybe helpful in the treatment of Diabetes Mellitus (DM) Type 2
(B) are released from I cells in the duodenum o Insulin secretion following a CHO-rich meal is stimulated by: GLP-1
(C) are members of the secretin-homologous family GIP, GLP-1 are INCRETIN HORMONES. INCRETIN EFFECT occurs when
(D) have five identical C-terminal amino acids ingested glucose has a greater effect on insulin secretion than injected
(E) have 90% homology of their amino acids From Physiology BRS, 6 Ed th
glucose. GIP, GLP-1 mediate this phenomenon.
Cholecystokinin (CCK) inhibits Effect of exercise on incretin: increases incretin. Exercise also increases
(A) gastric emptying GLUT4 translocation to the sarcolemma and t-tubule
(B) pancreatic HCO3– secretion Dr. Banzuela

(C) pancreatic enzyme secretion


(D) contraction of the gallbladder GI PARACRINES
(E) relaxation of the sphincter of Oddi From Physiology BRS, 6 Ed th • Somatostatin
Which of the following substances is secreted in response to an oral o Secreted by cells throughout the GI tract in response to H+
glucose load? o Inhibits release of ALL GI hormones
(A) Secretin o Inhibits gastric H+ secretion
(B) Gastrin
• Histamine
(C) Cholecystokinin (CCK)
(D) Vasoactive intestinal peptide (VIP) o Secreted by mast cells of gastric mucosa
(E) Glucose-dependent insulinotropic peptide (GIP) From Physiology BRS, 6 Ed th o Increases H+ secretion; potentiates gastrin and Ach action
Which of the following substances inhibits gastric emptying? o ranitidine inhibits: Histamine (H2) receptors
(A) Secretin Pronounce it this way: somatoSTOPin. Somatostatin is the ultimate
(B) Gastrin inhibitory hormone. Hypothalamic somatostatin inhibits Growth Hormone
(C) Cholecystokinin (CCK) (GH), Pancreatic somatostatin inhibits insulin and glucagon, and GIT
(D) Vasoactive intestinal peptide (VIP) somatostatin inhibits all GI hormones.
Dr. Banzuela
(E) Gastric inhibitory peptide (GIP) From Physiology BRS, 6 Ed th

Is Cholecystokinin (CCK) a neurotransmitter released by enteric neurons? NEUROCRINES


No (it is a GI Hormone) • VIP
Dr. Banzuela
o Relaxes Lower Esophageal Sphincter (LES), Orad Stomach,
CANDIDATE GI HORMONES Pyloric Sphincter, Ileocecal Valve
(NOT OFFICIALLY ACCEPTED AS GI HORMONES) o Stimulates HCO3- secretion and Inhibits gastric H secretion
• Pancreatic Polypeptide o Secreted by pancreatic islet cell tumors and involved in
o Secreted by pancreas in response to CHO, CHON, lipids pancreatic cholera
o Inhibits pancreatic HCO3- and enzyme secretion VIP is the ultimate smooth muscle relaxant – it relaxes the LES, Orad
• Enteroglucagon Stomach, PS and ICV. Mnemonic: kapag VIP ang bisita, dapat chillax siya
o Secreted by intestinal cells in response to hypoglycemia pagdating sa bahay nyo. VIP is a chillax substance – it provides smooth
muscle relaxation.
o Stimulates glycogenolysis and gluconeogenesis Dr. Banzuela

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• Enkephalins (met-enkephalin and leu-enkephalin) ELECTRICAL ACTIVITY OF GI SMOOTH MUSCLE
o Contracts LES, Pyloric Sphincter, Ileocecal Valve • Slow Waves
o Inhibits intestinal secretion of fluids and electrolytes (basis for o Not true action potentials
use of opiates in diarrhea) o Determine pattern of contraction
• GRP (Bombesin) o Slow, oscillating membrane potentials
o Stimulates gastrin release from G cells § Cyclic opening of Ca2+ channels (depolarization) followed by
✔GUIDE QUESTION opening of K+ channels (repolarization)
Which of the following substances is released from neurons in the GI tract o Due to Gastrointestinal Pacemaker: Interstitial Cells of Cajal
and produces smooth muscle relaxation? o Slowest Frequency: Stomach (3/min)
(A) Secretin (D) Vasoactive intestinal peptide o Fastest Frequency: Duodenum (12/min)
(B) Gastrin (VIP) • Spike Potentials
(C) Cholecystokinin (CCK) (E) Gastric inhibitory peptide (GIP) o True Action Potentials
From Physiology BRS, 6th Ed
o Depolarization: due to Calcium Influx
DESCRIPTION ANSWER o Threshold: -40Mv
Inhibits appetite; found at the
SATIETY CENTER
Ventromedial Hypothalamus
Stimulates appetite; found at the APPETITE/HUNGER
Lateral Hypothalamic Area CENTER
Sends signals to Satiety & Hunger
ARCUATE NUCLEUS
Centers
ANOREXIGENIC
Releases POMC to decrease appetite
NEURONS
Releases Neuropeptide Y to increase OREXIGENIC
© Topnotch Medical Board Prep
appetite NEURONS Remember: slow waves are NOT true action potentials. They only bring you
Stimulates Anorexigenic Neurons, closer to threshold. Spike potentials are true action potentials. Slow waves
LEPTIN, INSULIN,
inhibits orexigenic Neurons; are produced by the interstitial cells of Cajal (the GI Pacemaker), slowest
GLP-1
secreted by fat cells frequency in the stomach, fastest in the duodenum.
Dr. Banzuela
Inhibits Anorexigenic Neurons;
GHRELIN ✔GUIDE QUESTION
secreted by gastric cells
Inhibits Ghrelin PEPTIDE YY Slow waves in small intestinal smooth muscle cells are
(A) action potentials
If you damage the ventromedial hypothalamic area will the patient have (B) phasic contractions
weight gain or weight loss? Answer: weight Gain. Ventromedial (C) tonic contractions
hypothalamus is the satiety center. If that is destroyed, patient would be (D) oscillating resting membrane potentials
less satiated (less busog), so patient would eat more, and then gain weight. (E) oscillating release of cholecystokinin (CCK)
Leptin (from the Greek word “leptos” meaning thin) decreases food intake
SPECIAL NOTES ON PERISTALSIS
(through its anorexigenic effect) and may also increase energy
expenditure. • Most common stimulus for GI peristalsis: Distention
Which hormone is not produced in the gastric organ - ghrelin, intrinic • Composition of Myenteric Reflex: Muscles Upstream (nearer the
factor (IF), pepsin, motilin? mouth) will contract, Muscles Downstream (nearer the anus) will
A: Motilin - it is hormone secreted by M cells of the duodenum and jejunum. exhibit receptive relation
Pepsin is an enzyme, not a hormone. Ghrelin is secreted BY THE STOMACH • Time to transfer material from pylorus to ileocecal valve: 3-5 hours
referred to as the "hunger hormone". IF is not a hormone but it is produced • Time to transfer material from ileocecal valve to colon: 8-15 hours
by parietal cells of stomach • Pattern of GI motor function in fasting: Migrating
Dr. Banzuela
(interdigestive) Motor Complex
MNEMONICS APPETITE
• Cross-Over questions:
VENTROMEDIAL: “VUCHOG” o Double bubble sign: Duodenal Atresia
Satiety Center o Apple core sing (also called napkin ring sign): Stenosing
LATERAL: “LAMON” annular colorectal carcinoma
Hunger Center
CHEWING
6.3. GI MOTILITY • Maybe voluntary or involuntary
• Functions:
• Contractile Tissue in the GI tract is made up of Unitary Smooth
o Lubricates food with saliva
Muscles EXCEPT:
o Decreases size of food particles
o Pharynx
o Amylase begins CHO digestion
o Upper 1/3 of Esophagus
o External Anal Sphincter SWALLOWING
§ Depolarization of Circular Muscle: decreases diameter of • Swallowing Center: Medulla (utilizing CN IX and X)
that segment 1. Oral Phase: triggers reflex when food is at the pharynx
§ Depolarization of Longitudinal Muscle: decreases length of 2. Pharyngeal Phase: soft palate pulled upward (closes
that segment nasopharynx), glottis covered (prevents aspiration), Upper
Esophageal Sphincter (UES) relaxes
GI SMOOTH MUSCLE CONTRACTIONS 3. Esophageal Phase: UES closes, Primary and Secondary
TONIC CONTRACTIONS PHASIC CONTRACTIONS Esophageal Peristalsis occurs
• Constant level of contraction • Periodic contractions
or tone without regular followed by relaxation
periods of relaxation • For mixing and propulsion
• Orad (upper) region of the • Seen in the esophagus,
stomach and in the lower gastric antrum, small
esophageal, ileocecal and intestines
internal anal sphincters • Due to spike potentials
• Due to subthreshold slow
waves
Tonic contractions are TONICALLY (continuously) contracted. Think
Sphincters. Tonic Contractions are caused by SLOW WAVES. Phasic
contraction are contractions in PHASES (alternate contraction and
relaxation). Phasic contractions are caused by SPIKE POTENTIALS.
Dr. Banzuela

© Topnotch Medical Board Prep

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TOPNOTCH MEDICAL BOARD PREP PHYSIOLOGY MAIN HANDOUT BY DR. ENRICO PAOLO C. BANZUELA
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This handout is only valid for October 2023 PLE batch. This will be rendered obsolete for the next batch since we update our handouts regularly.

ESOPHAGEAL PERISTALSIS
• Primary Peristaltic Contraction
o Creates high pressure behind bolus of food propelling it towards
the stomach
o Accelerated by Gravity (you don’t need gravity to swallow, since
the pressure is high enough to put bolus into the stomach;
gravity assists though)
• Relaxation of the Lower Esophageal Sphincter (LES)
o Utilizes VIP and NO from inhibitory ganglionic neurons
• Receptive Relaxation of the Orad Stomach
o Food enters the stomach
• Secondary Peristaltic Contraction
o Clears esophagus of remaining food
o Gastric acid reflux into the esophagus triggers: secondary
esophageal peristalsis
• In Achalasia, esophageal myenteric plexus is deficient, NO and
VIP is deficient (due to decreased expression of neuronal NO © Topnotch Medical Board Prep

synthase) à no anterograde/receptive relaxation ahead of the


stimulus
• 49/F vomiting shortly after eating has normal rate of liquid
emptying but prolonged time for emptying of solids. Diagnosis:
Pyloric Stenosis
REMEMBER! ESOPHAGEAL PRESSURES
Intraesophageal Pressure = Intrathoracic Pressure.
Intraesophageal Pressure < Atmospheric Pressure.
You can swallow food upside down (against gravity)
Gravity assists, but is not a necessity, in swallowing
Dr. Banzuela

GASTRIC MOTILITY
• Stomach action for mixing of food: peristalsis
• VIP, CCK: facilitates Receptive Relaxation of Orad Stomach
o Fundus and upper portion of the stomach body relaxes © Topnotch Medical Board Prep

o Receptive Relaxation of the stomach is the reason why gastric ✔GUIDE QUESTION
pressure seldom rise above the levels that breach the LES even A 24-year-old male graduate student participates in a clinical research
study on intestinal motility. Peristalsis of the small intestine
if stomach is filled with meal (A) mixes the food bolus
• Parasympathetic NS (via VN X): stimulates gastric contractions (B) is coordinated by the central nervous system (CNS)
• Capacity of Stomach: 1.5L (C) involves contraction of smooth muscle behind and in front of the
• Motilin: stimulates gastric contractions (MMC) every 90 food bolus
minutes to help clear stomach of residual food (D) involves contraction of smooth muscle behind the food bolus
• Retropulsion: food in the caudad stomach going back to orad and relaxation of smooth muscle in front of the bolus
(E) involves relaxation of smooth muscle simultaneously throughout
stomach for further mixing and digestion
the small intestine From Physiology BRS, 6 Ed
th

Gastric emptying: movement of material from stomach to


duodenum; takes approximately 3 hours
LARGE INTESTINAL MOTILITY
INCREASES GASTRIC DECREASES GASTRIC
• Ileocecal valve: prevents reflux into the ileum
EMPTYING EMPTYING
• Proximal Colon: for absorption of water
Increased GASTRIC volume Increased DUODENAL volume
• Distal Colon: for storage of feces
Hypertonic & Hypotonic
Isotonic content • Segmentation Contractions (Haustrations): responsible for the
content
appearance of Haustra (sac-like structures in the colon)
Chyme Formation Fat in the duodenum
• Mass movements: occur 1-3x a day to move colonic contents over
HCl in the duodenum (acids)
long distances
✔GUIDE QUESTION • Emotions: influences large intestinal motility via extrinsic ANS
Which of the following abolishes “receptive relaxation” of the stomach? o May cause diarrhea or constipation
(A) Parasympathetic stimulation
(B) Sympathetic stimulation
(C) Vagotomy
(D) Administration of gastrin
(E) Administration of vasoactive intestinal peptide (VIP)
From Physiology BRS, 6th Ed
Receptive relaxation of the orad stomach occurs using a vagovagal
reflex. Vagotomy would prevent that.
Dr. Banzuela

SMALL INTESTINAL MOTILITY


• Food that enter the small intestines: Chyme (partially digested
food due to stomach action)
• Segmentation Contraction
o Back-and-forth movement with no net forward motion
o Mixes chyme with pancreatic enzymes
• Peristaltic Contraction
o Propels chyme towards large intestines
§ rhythmic phasic contraction propels chyme in a unilateral
direction
o (+) contraction behind bolus and (+) relaxation in front of bolus © Topnotch Medical Board Prep

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DEFECATION o Gastrocolic reflex is the reason why in infants, defecation


often follows a meal
• Urge to defecate occurs once rectum is 25% filled
o Cause of normal bowel movements in newborns: gastrocolic
• Gas from colon is primarily derived from: Fermentation of
reflex
undigested oligosaccharides
• Internal Anal Sphincter VOMITING
o Involuntary • Wave of reverse peristalsis (orad direction) that begins from the
o Relaxed by rectal contents (rectosphincteric reflex) Small Intestines
• External Anal Sphincter • Preceded usually by Nausea
o Voluntary • Vomiting Center: Medulla
o Must be relaxed by the person for defecation to occur o Receives info from the vestibular system, back of the throat,
• Valsalva Maneuver GI tract and the Chemoreceptor Trigger Zone
o Expiring against a closed glottis (increasing intra-abdominal o Location of the chemoreceptor Trigger Zone: Area Postrema
pressure) § Triggers
o Assists in defecation 1. Emetics
• Encopresis 2. Radiation
o repeated involuntary passing of stool into clothing by children 3. Vestibular stimulation
Urge to defecate once rectum is 25% filled. Urge to urinate occurs once • incomplete vomiting due to Closed UES: Retching
urinary bladder is 25% filled. External anal sphincter is voluntary, internal
anal sphincter is involuntary. External urethral sphincter is voluntary, 6.4 GI SECRETION
internal urethral sphincter is involuntary. Both external and internal anal
sphincters must relax for defecation to occur. Both external and internal GASTRO-INTESTINAL JUICES
urethral sphincters must relax for urination to occur. DAILY
TYPE PH
Dr. Banzuela VOLUME (ML)
✔GUIDE QUESTION Saliva 1000 6.0-7.0
Which of the following changes occurs during defecation? Gastric Secretion 1500 1.0-3.5
(A) Internal anal sphincter is relaxed Pancreatic Secretion 1000 8.0-8.3
(B) External anal sphincter is contracted Bile 1000 7.8
(C) Rectal smooth muscle is relaxed
(D) Intra-abdominal pressure is lower than when at rest
S.I. Secretion 1800 7.5-8.0
(E) Segmentation contractions predominate Brunner’s Gland Secretion 200 8.0-8.9
From Physiology BRS, 6th Ed L.I Secretion 200 7.5-8.0
TOTAL 6700
GASTROILEAL & GASTROCOLIC REFLEX In Ganong 25-3, Pancreatic Juice is the most basic (alkaline) simply
• Gastroileal Reflex because there is no Brunner Gland Secretion in the choices. If there is,
o Triggers increases peristalsis in the ileum Brunner Gland secretion is the correct answer.
o Food in the stomach increases peristalsis in the ileum and Remember the “magic number 1.5L”: you produce 1.5L of HCl per day, 1.5L
relaxation of the ileocecal sphincter of water is absorbed in the large intestines to dry up the feces, and 1.5L is the
capacity of the stomach. All previous med boards questions from years ago.
• Gastrocolic Reflex Dr. Banzuela
o Food in the stomach increases peristalsis in the colon and
frequency of mass movements
§ Mediated by the Parasympathetic NS, CCK, Gastrin
SUMMARY OF GASTROINTESTINAL (GI) SECRETIONS
GI SECRETION MAJOR CHARACTERISTICS STIMULATED BY INHIBITED BY
• High HCO3-
• High K+ • Sleep
• Parasympathetic nervous system
Saliva • Hypotonic • Dehydration
• Sympathetic nervous system
• ⍺-Amylase • Atropine
• Lingual lipase
• ↓ Stomach pH
• Gastrin • Chyme in duodenum (via secretin and GIP)
• HCl • Parasympathetic nervous system • Somatostatin
Gastric
• Histamine • Atropine
secretion
• Cimetidine, Omeprazole
• Pepsinogen • Parasympathetic nervous system -
• Intrinsic Factor - -
• Secretin
• High HCO3-
• CCK (potentiates secretin) -
Pancreatic • Isotonic
• Parasympathetic nervous system
secretion
• Pancreatic lipase, • CCK
-
amylase, proteases • Parasympathetic nervous system
• CCK (causes contraction of
• Bile salts
gallbladder and relaxation of
• Bilirubin
Bile sphincter of Oddi) • Ileal resection
• Phospholipids
• Parasympathetic nervous system
• Cholesterol
(causes contraction of gallbladder)
CCK = Cholecystokinin; GIP = glucose-dependent insulinotropic peptide
SALIVA • Inhibited by:
• Formed mainly by parotid, submandibular and sublingual o Sleep, dehydration, fear, anticholinergic drugs
glands Refer to the next picture and table as you listen to this audio recording
• Composition: regarding salivation:
o High volume relative to salivary gland size
o High K and HCO3-
o Low Na and Cl SALIVATION
o Hypotonic https://qrs.ly/uhebjhg
o (+) amylase, lingual lipase and kallikrein
• Increased by: Dr. Banzuela

o Food in the mouth, smells, conditioned reflexes, nausea

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HCL SECRETION

© Topnotch Medical Board Prep


DESCRIPTION ANSWER
Effect of Parasympathetic NS INCREASES SALIVATION
Effect of Sympathetic NS INCREASES SALIVATION
Initial Saliva is high in: Na+, Cl-
Final Saliva is high in: HCO3-, K+
Hormone involved in
absorbing Na+ at the ductal ALDOSTERONE
cells © Topnotch Medical Board Prep

HIGH Na+, Cl-, LOW K+ & Refer to the picture above as we discuss HCl secretion in the stomach using
At High Flow Rates, Saliva has the audio recording below:
HIGH HCO3
LOW Na+, Cl -, HIGH K+ &
At Low Flow Rates, Saliva has HCl SECRETION
LOW HCO3-
PARASYMPATHETIC IN THE STOMACH
Salivation upon seeing NERVOUS SYSTEM https://qrs.ly/5jebjho
roasted pig is caused by (cephalic phase of gastric secretion
also occurs at this time) Dr. Banzuela

• Characteristic of Gastric HCl


✔GUIDE QUESTION o pH of 0.8
Which of the following is characteristic of saliva?
o secreted at rate of 160 millimoles per L
(A) Hypotonicity relative to plasma
(B) A lower HCO3– concentration than plasma
o hydrogen concentration 3 million times higher than arterial
(C) The presence of proteases blood
(D) Secretion rate that is increased by vagotomy • Factors that promoted HCl Secretion and the receptors that they
(E) Modification by the salivary ductal cells involves reabsorption of bind to:
K+ and HCO3– From Physiology BRS, 6 Ed th
Factor Receptor
It’s hypotonic because of the low Na concentration. Histamine H2 receptors
Dr. Banzuela
Acetylcholine (ACh) M3 receptors
GASTRIC CELLS & SECRETIONS Gastrin CCKB receptors
DESCRIPTION ANSWER o Note: above 3 factors can potentiate (total effect greater than
Contains Mucus Neck Cells, the sum of the individual parts)
OXYNTIC GLANDS (BODY) o Basal acid output is increased by: alkalinization of antrum
Parietal Cells and Chief Cells
(releases gastrin-releasing cells from inhibitory influence of somatostatin)
PYLORIC GLANDS
Contains G Cells, Mucus Cells • Factors that inhibit HCl Secretion
(ANTRUM)
o Low pH (<3.0) of the stomach, somatostatin, prostaglandins
MUCUS CELLS, MUCUS NECK
Secretes Mucus and HCO3- • Phases:
CELLS
o Cephalic Phase (30%), Gastric Phase (60%) and Intestinal Phase
PARIETAL CELLS/OXYNTIC
Secretes HCl and IF (10%)
CELLS
Secretes Gastrin G CELLS Sight, smell, taste of food (cephalic phase) contributes to INCREASED
gastric/HCl secretion.
ENTEROCHROMAFFIN
Low gastric pH (e.g., gastric pH<3.0) contributes to DECREASED
Secretes Serotonin CELLS OR KULCHITSKY gastric/HCl secretion
CELLS MOA of prostaglandins inhibiting gastric HCl secretion: inhibition of
ENTEROCHROMAFFIN-LIKE release of gastrin and histamine.
Secretes Histamine
(ECL) CELLS Dr. Banzuela

CHIEF / PEPTIC / • Drugs that block HCl secretion


Secretes Pepsinogen o Atropine on M3, Cimetidine on H2 and PPI (Omeprazole) on H+-
ZYMOGENIC CELLS
K+-ATPase exchange pump
Found in the basement membrane of the bronchi and bronchioles: o Best describes H2 blockers: inhibits both gastrin- and
bronchial Kulchitsky cell (pulmonary neuroendocrine cells)
Found in the small intestines, colon, appendix: GI Kulchitsky cells
acetylcholine-mediated secretion of acid
Dr. Banzuela ✔GUIDE QUESTIONS
✔GUIDE QUESTIONS Secretion of which of the following substances is inhibited by low pH?
(A) Secretin
Which of the following is the site of secretion of intrinsic factor?
(B) Gastrin
(A) Gastric antrum (D) Ileum
(C) Cholecystokinin (CCK)
(B) Gastric fundus (E) Colon
From Physiology BRS, 6 Ed (D) Vasoactive intestinal peptide (VIP)
(C) Duodenum th

(E) Gastric inhibitory peptide (GIP) From Physiology BRS, 6 Ed th

IF is the only essential secretion of the stomach. It is essential because A patient with a duodenal ulcer is treated successfully with the drug
we need it to absorb Vitamin B12 (this vitamin is needed for proper DNA cimetidine. The basis for cimetidine’s inhibition of gastric H+ secretion is
synthesis) that it
Dr. Banzuela
(A) blocks muscarinic receptors on parietal cells
Which of the following is the site of secretion of gastrin? (B) blocks H2 receptors on parietal cells
(A) Gastric antrum (D) Ileum (C) increases intracellular cyclic adenosine monophosphate (cAMP)
(B) Gastric fundus (E) Colon levels
From Physiology BRS, 6 Ed
(C) Duodenum th

(D) blocks H+, K+-adenosine triphosphatase (ATPase)


When parietal cells are stimulated, they secrete (E) enhances the action of acetylcholine (ACh) on parietal cells
(A) HCl and intrinsic factor (D) HCO3– and intrinsic factor From Physiology BRS, 6th Ed
(B) HCl and pepsinogen (E) mucus and pepsinogen A patient with Zollinger–Ellison syndrome would be expected to have
From Physiology BRS, 6 Ed
(C) HCl and HCO3– th
which of the following changes?
(A) Decreased serum gastrin levels
(B) Increased serum insulin levels
(C) Increased absorption of dietary lipids
(D) Decreased parietal cell mass
(E) Peptic ulcer disease From Physiology BRS, 6 Ed th

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CLINICAL CORRELATES ZOLLINGER-ELLISON SYNDROME
Gastrinoma → High levels of Gastrin → (+) hypersecretion of HCl
→ severe ulcers formed

EXOCRINE PANCREATIC SECRETION


• Characteristics
o High Volume
o Much higher HCO3- than plasma (counteracts acids in
duodenum)
o Isotonic
o Same Na and K as plasma
o Lower Cl than plasma
o Contains pancreatic amylase, lipase (also called carboxylic
esterase), protease, trypsin inhibitor
§ Steatorrhea in patients with pancreatitis is secondary to
decrease in luminal levels of: pancreatic lipase
o Also has cephalic, gastric and intestinal phase
o Substrates of pancreatic enzymes: Triglycerides, proteins,
carbohydrates © Topnotch Medical Board Prep
• Stimulated by • Bile is stored AND concentrated in the Gallbladder
o Secretin • CCK and Ach causes GB contraction
§ Secreted by S Cells • CCK causes Sphincter of Oddi Relaxation
§ Acts on ductal cells • Bile is release in “pulsatile spurts” due to intermittent
§ Increases HCO3- secretion contraction of the duodenum
§ 2nd messenger: cAMP • 94% Bile salts are recirculated back to the liver using Na-Bile salt
o Cholecystokinin (CCK) cotransporter in the terminal ileum (enterohepatic circulation)
§ Secreted by I Cells o Removal of terminal ileum results in: steatorrhea (Increased
§ Acts on CCKA receptors in acinar cells and ductal cells to excretion of fatty acids)
increase enzyme secretion o Best describes bile acid function: The amount lost in the stool
§ Potentiates effect of secretin in increasing HCO3- secretion each day represents the daily loss of cholesterol
§ 2nd messenger: IP3-DAG o Surgical resection of Ileum would cause: Increase in water
o Acetylcholine (Ach) content of feces
§ Via vagovagal reflexes o Protects duodenal mucosa from gastric acid: Bicarbonate
§ Acts on muscarinic receptors in acinar cells and ductal cells to contained in bile
stimulate enzyme secretion • Gallbladder has:
§ Also potentiates effect of secretin in increasing HCO3- o ↑ Na+, Ca2+, Bile Salts, Cholesterol, Lecithin concentration
secretion o ↓ Cl- and HCO3- concentration
✔GUIDE QUESTION
Which of the following is true about the secretion from the exocrine
pancreas?
(A) It has a higher Cl– concentration than does plasma
(B) It is stimulated by the presence of HCO3– in the duodenum
(C) Pancreatic HCO3– secretion is increased by gastrin
(D) Pancreatic enzyme secretion is increased by cholecystokinin
(CCK)
(E) It is hypotonic From Physiology BRS, 6 Ed th

CLINICAL CORRELATES PANCREATECTOMY


Pancreatectomy is associated with:
• Loss of exocrine pancreatic secretions → steatorrhea and
protein malabsorption
• Loss of insulin secretion:
o High glucagon/insulin ratio → hyperglycemia
o ↓ intracellular uptake of glucose, ↑ protein and fat catabolism
→ weight loss (instead of weight gain)
§ ↑ ketone production and use → metabolic acidosis
BILE
• Most common component: Water
• Active Component: Bile Salts
o Bile salts are formed from Cholesterol
• Bile Salts: Amphipathic © Topnotch Medical Board Prep

o Emulsify Fats ✔GUIDE QUESTION


o Forms Micelles for fat absorption Which of the following is the site of Na+–bile acid cotransport?
(A) Gastric antrum (D) Ileum
o biles salts are the only way to remove cholesterol from the body
(B) Gastric fundus (E) Colon
• Other Components: (C) Duodenum From Physiology BRS, 6
th Ed

o Bilirubin, Cholesterol, Phospholipids, Electrolytes


Like surfactant, bile salts are AMPHIPATHIC – they have a lipid-soluble side 6.5 DIGESTION AND ABSORPTION
and a water-soluble side. They are basically both DETERGENTS –
substances that can help dissolve lipids in water. The process of DIGESTION OF CARBOHYDRATES
emulsification basically means you make large lipid droplets into smaller • Salivary and Pancreatic Amylase: hydrolyzes 𝛼1,4-glycosidic
lipid droplets. This would happen when bile salts surround the large lipid bonds in starch yielding maltose, maltotriose and 𝛼-limit dextrins
droplets → when you dissolve the large lipid droplets in water, you make • Intestinal brush border Maltase, 𝛼-dextrinase and sucrase:
smaller lipid droplets. Smaller lipid droplets mean they are easier to
degrade oligosaccharides to glucose
absorb and be acted upon by pancreatic lipase. Think of Bile Salts as
something similar to Joy dishwashing fluid (“isang patak, tanggal sebong • Lactase, trehalase and sucrase: degrades disaccharides to
sangkatutak”) – emulsification is about breaking down fat into smaller monosaccharides
lipid droplets using detergent action.
Dr. Banzuela

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© Topnotch Medical Board Prep


CLINICAL CORRELATES DUMPING SYNDROME
• Gastric Bypass → loss of “reservoir function” of stomach → if
patient eats large meals → rapid absorption of glucose in the
intestines → hyperglycemia → insulin secretion →
HYPOGLYCEMIA 2 hours after meals presenting as weakness
dizziness and sweating (DUMPING SYNDROME)
• After gastric bypass surgery, patients presents with crampy
abdominal discomfort 15-30 mins after meals, with nausea,
diarrhea, belching, tachycardia, palpitations, diaphoresis,
light-headedness. These symptoms most likely arise from:
© Topnotch Medical Board Prep Release of VIP and motilin
ABSORPTION OF CARBOHYDRATES DIGESTION OF PROTEINS
• Only Monosaccharides are absorbed • Brush border enzyme Enterokinase (also called
• Luminal Side: ENTEROPEPTIDASE) is required for PROTEIN ASSIMILATION
o SGLT-1 (secondary active transport): for glucose and • Endopeptidases: degrade proteins from interior peptide bonds
galactose • Exopeptidases: degrade proteins from the” edge” of the protein
§ Remember: competitive inhibitor of glucose in the small (C terminus)
intestines: Galactose
• Pepsin:
o GLUT-5 (facilitated diffusion): for fructose
o inessential protease initially (pepsinogen)
• Basolateral Side: o secreted by Chief Cells of stomach, activated by gastric H+
o GLUT-2 (facilitated diffusion): all types of monosaccharides o ACTIVE (optimum pH) at pH 1-3
Again, with feelings: only monosaccharides (glucose, galactose, fructose)
o INACTIVE (denatured) at pH of 5
can be absorbed in the small intestines. We cannot absorb disaccharides
or polysaccharides. SGLT-1 is used to absorb glu/gal from lumen to • Pancreatic Proteases (essential): trypsin, chymotrypsin,
intestinal cell, GLUT-5 for fru from lumen to intestinal cell. GLUT-2 is used elastase, carboxypeptidase A and B
to absorb glu/gal/fru from intestinal cell to the blood. Pepsin and HCl are considered “inessential” – you can live without them –
Carbohydrate absorption begins in the small intestines (carbohydrate they merely supplement pancreatic proteases. The pancreatic protease
DIGESTION begins in the mouth because of ptyalin) Trypsin is the one considered “essential” – this is the one that does most of
Q:Energy used in sodium-glucose transport? the work in terms of proteolysis. Once you have Trypsin, it can activate the
A: Na downhill transport other zymogens (inactive proteases) including other trypsinogen
Q:What is the main souce of starch in humans? molecules, chymotrypsinogen, proelastase, procarboxypeptidase.
Dr. Banzuela
A: Amylopectin (natural starches: 10%–30% amylose and 70%–90%
amylopectin) ABSORPTION OF PROTEINS
Q:Gluten-free grain?
• Free Amino Acids (AA)
A: Rice (wheat, barley and rye have gluten) o Luminal Membrane: Na-AA (amino acid) symport
Dr. Banzuela o Basolateral Membrane: facilitated diffusion
✔GUIDE QUESTION o 4 separate carriers for neutral, acidic, basic and imino acids
Which of the following substances must be further digested before it can o Sites of Amino acid absorption: Duodenum, jejunum, ileum
be absorbed by specific carriers in intestinal cells? • Dipeptides and Tripeptides
(A) Fructose (D) Dipeptides o Absorbed faster than free AA
(B) Sucrose (E) Tripeptides o Luminal Membrane: H+-dipeptide/tripeptide symport
From Physiology BRS, 6 Ed
(C) Alanine th

o Intestinal Cells: Cytoplasmic peptidases degrade them into


free AA
o Basolateral Membrane: Facilitated diffusion of free AA
✔GUIDE QUESTION
Which of the following is transported in intestinal epithelial cells by a
Na+-dependent cotransport process?
(A) Fatty acids (D) Alanine
(B) Triglycerides (E) Oligopeptides
From Physiology BRS, 6 Ed
(C) Fructose th

© Topnotch Medical Board Prep

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© Topnotch Medical Board Prep


DIGESTION OF LIPIDS
• Triglyceride, Cholesterol Esters and Phospholipids are broken
down as they enter the intestinal cells and then recreated as they
exit
• Enter intestinal cells via: Micelles
• Leave intestinal cells via: Chylomicrons
• Steatorrhea is seen in:
o Pancreatic Disease (e.g., pancreatitis, cystic fibrosis):
insufficient pancreatic lipase
§ Describes pancreatic function in patients with acute
pancreatitis: Phospholipase A2 maybe prematurely
activated by trypsin
o Gastrinoma: resulting low duodenal pH inactivates pancreatic
lipase
o Ileal resection: insufficient bile acid pool
o Bacterial overgrowth: deconjugation of bile acids
o Tropical Sprue: decrease surface area for lipid absorption
o Inability to synthesize apoprotein B: inability to form
chylomicrons

✔GUIDE QUESTION
A 49-year-old male patient with severe Crohn disease has been
unresponsive to drug therapy and undergoes ileal resection. After the
surgery, he will have steatorrhea because
(A) the liver bile acid pool increases
(B) chylomicrons do not form in the intestinal lumen
(C) micelles do not form in the intestinal lumen
(D) dietary triglycerides cannot be digested
(E) the pancreas does not secrete lipase From Physiology BRS, 6 Ed th

• Consequence of ileal resection: Bile acids excreted into the


feces
• Will be seen in Crohn disease with ileal inflammation:
Decreased bile acid pool size
Refer to the two pictures below as we discuss absorption of lipids using this
audio recording:
© Topnotch Medical Board Prep
WATER AND ELECTROLYTES
ABSORPTION OF LIPIDS DESCRIPTION
https://qrs.ly/ftebjkh • Small Intestine (S.I.): SGLT-1, Na-aa, NaCl
Na+ symport, Na+-H+ antiport
Dr. Banzuela absorption • Large Intestines (L.I): passive diffusion
(paracellular route, stimulated by aldosterone)
• Accompanies Na+ via Passive diffusion
Cl-
(paracellular route), Na-Cl symport, Cl-HCO3-
absorption
antiport
• S.I.: passive diffusion (paracellular route)
K+
• L.I.: active secretion (stimulated by
absorption
aldosterone)
• Secondary to solute absorption
H2O
• S.I. and Gallbladder: isosmotic
absorption
• L.I.: lower water permeability compared to S.I.
• Primary ion secreted in the GI tract: Chloride
• Utilizes Cl- channels in the luminal membrane
Cl-
regulated by cAMP
secretion
© Topnotch Medical Board Prep
• Na is secreted into lumen passively follows Cl.
Water then follows NaCl
• Best describes water and electrolyte absorption: majority
happens in the jejunum
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OTHER SUBSTANCES • Kupffer Cells
NUTRIENT DESCRIPTION o Found in the liver sinusoids and act as antigen-presenting cells
Produced by bacteria o Kupffer cells protects against sepsis secondary to translocation
Short-Chain Fatty
Absorption almost exclusively happens in of intestinal bacteria
Acids
the: colon CLINICAL CORRELATES UROBILINOGEN
Fat-Soluble Incorporated into micelles and absorbed
• Colectomy → antibowel preparation + resection of entire colon
Vitamins (ADEK) with lipids
→ ↓ colonic bacteria → ↓ deconjugation of bacteria →
Water-Soluble
Na+-dependent symport ↓absorption of urobilinogen → ↓ urobilinogen excretion in the
Vitamins
urine
Absorbed in Ileum using Intrinsic Factor
• Found in patients with infectious hepatitis: increase in both
(IF)
direct and indirect bilirubin
*Vit B12 deficiency + pernicious anemia is caused
Vitamin B12
by: Lack of IF
*MOA of neurologic deficits in Vit B12 deficiency:
Decreased myelin synthesis
1,25 dihydroxycholecalciferol → ↑
Calcium
calbindin D-28K → ↑calcium absorption
Heme Iron broken down in intestinal cells
→ Free Fe2+ binds to apoferritin and
Iron
transported in blood → Free Fe2+ binds to
transferrin in blood
Remember: Sites of absorption: duodenum – iron and Vitamin C. Jejunum
– fat, proteins, carbohydrates, water. Ileum – Vitamin ADEK, IF-B12
complex, Bile Salts.
Dr. Banzuela
Daily Water Turnover in the GI Tract
Ingested 2000
Endogenous
7000
secretions
Salivary glands 1500
Stomach 2500
Bile 500
Pancreas 1500
Intestine +1000
7000
Total Input 9000
Reabsorbed 8800
Jejunum 5500
Ileum 2000
Colon +1300
8800
Balance in tool 200
Adapted from Figure 25-5. Barrett et al. Ganong’s Review of Medical Physiology. 26th ed. 2019

CLINICAL CORRELATES CHOLERA


Cholera toxin → increase cAMP → opens chloride channels →
chloride ions secretion → activate a sodium pump → secretion of
sodium ions → NaCl formed in the crypts → extreme osmosis of
water from the blood into the intestinal lumen.

✔GUIDE QUESTIONS
Vibrio cholerae causes diarrhea because it
(A) increases HCO3– secretory channels in intestinal epithelial cells
(B) increases Cl– secretory channels in crypt cells © Topnotch Medical Board Prep

(C) prevents the absorption of glucose and causes water to be Do not confuse bilirubin with bile salts. Bilirubin is a breakdown product of
retained in the intestinal lumen isosmotically heme and RBCs and give the urine and feces its yellow color. Bile Salts come
(D) inhibits cyclic adenosine monophosphate (cAMP) production in from cholesterol, and is used for emulsification of fats.
intestinal epithelial cells Dr. Banzuela
(E) inhibits inositol 1,4,5-triphosphate (IP3) production in intestinal
epithelial cells From Physiology BRS, 6 Ed
7. ENDOCRINE AND REPRODUCTIVE
th

Micelle formation is necessary for the intestinal absorption of


(A) glycerol (C) bile acids PHYSIOLOGY
(B) galactose (D) vitamin B12 1. Overview of Hormones
(E) vitamin D 2. Cell Mechanisms and Second Messengers
From Physiology BRS, 6th Ed
3. Pituitary Gland
4. Thyroid Gland
6.6 LIVER PHYSIOLOGY 5. Adrenal Cortex and Adrenal Medulla
LIVER 6. Endocrine Pancreas-Glucagon and Insulin
7. Calcium Metabolism
• Central Organ of Biochemistry
8. Sexual Differentiation
• Cytochrome P450 Enzymes 9. Male Reproduction
o Superfamily of enzymes that inactivates/activates xenobiotics 10. Female Reproduction
o Important role in the following
Listen to this audio recording while reading the next section on the types of
§ Bile acid formation hormones and hormone regulation:
§ Carcinogenesis
§ Steroid hormone formation
TYPES OF HORMONES
§ Detoxification of drugs
AND HORMONE REGULATION
• Stellate cells of Ito (found in perisinusoidal space of Disse)
https://qrs.ly/62ebjl2
o Responsible for vitamin A storage
o Responsible for liver fibrosis (when regeneration potential of Dr. Banzuela
liver has reached its limit)
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7.1 OVERVIEW OF HORMONES


HORMONES
• Chemical messengers released into the blood
• Hormone that enters the cell and binds with a protein inside: Lipid-
soluble hormones (e.g., thyroid hormone, adrenocortical hormones)
PROTEIN HORMONE LIPID HORMONE
(WATER-SOLUBLE) (LIPID-SOLUBLE)
Location of Cell Membrane Nuclear / Cytoplasmic
receptors Receptors Receptors
Mechanism Utilizes G Proteins Causes transcription of
of action and 2nd messengers Genes
Activates existing
Synthesizes new
Final Effect intracellular enzymes
intracellular enzymes
via phosphorylation
• Aldosterone,
• Insulin,
• Cortisol,
Examples • Glucagon,
• Sex Hormones,
• Growth Hormone
• Vitamin D
Remember: Hormones that crosses the cell membrane: STEROID
HORMONES. This would include aldosterone, cortisol, sex hormones and © Topnotch Medical Board Prep
Vitamin D
Dr. Banzuela
HORMONE SYNTHESIS: PEPTIDE AND PROTEIN HORMONES

© Topnotch Medical Board Prep

7.2 CELL MECHANISMS AND SECOND MESSENGERS


Listen to this audio recording while reading the section on G proteins and
2nd messenger systems below:

G PROTEINS AND
2ND MESSENGER SYSTEMS
https://qrs.ly/p6ebjld
© Topnotch Medical Board Prep
HORMONE REGULATION Dr. Banzuela

• Hormone Secretion Regulation G-PROTEINS


o Negative-Feedback: limits final products (e.g., Insulin and • ” Guanosine Triphosphate (GTP)-activated” proteins
Blood Glucose) • “Transducers” (bridges): couple 1st messenger (hormone or NT
o Positive-Feedback: increases final products (e.g., Oxytocin binding to cell membrane receptor) with the 2nd messenger (2nd
during breastfeeding and delivery, estrogen-induced LH and messenger systems like cAMP and IP3/DAG)
FSH surge during ovulation) • 3 subunits: α, β, and γ
• Hormone Receptor Regulation o Most important: α subunit – binds with GDP (inactivates G
o Upregulation: increase in receptor number or sensitivity (e.g., protein) or GTP (activates G protein)
uterus: estrogen upregulating estrogen receptor (its own o GTP: stimulated by GEFs and inhibited by GAPS and RGS
receptor) and LH receptor) proteins
o Downregulation: decrease in receptor number or sensitivity
• Gs or Gi: depends on presence of αs or αi
(e.g., uterus: progesterone downregulating progesterone
receptors (its own receptors) and estrogen receptor)
2ND MESSENGERS
Important in the feedback mechanism of controlling hormone secretion:
secretory rate. • Mediate the intracellular responses to many different hormones
True of endocrine hormones: number of target tissue receptors does not and neurotransmitters
remain constant day to day (upregulation and downregulation exists) • Remember the sequence:
Dr. Banzuela
o 1st messenger (hormone/NT) → G-protein coupled receptors
(cell membrane receptors!) for hormones/NTs → G Proteins →
2nd Messengers →→→ kinases → activated enzyme →
intracellular response

cAMP 2nd MESSENGER SYSTEM


• Most common 2nd messenger system
• Mnemonic: Alpha subunit of G proteins activates Adenylate cyclase
converts ATP to cAMP → activates Protein Kinase A (PKA)

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• Receptor Tyrosine Kinase
o e.g., in NGF (monomer receptor) and Insulin, IGF (dimeric
receptor)
o Hormone binds to cell membrane receptor → intracellular
tyrosine kinase activated → phosphorylation of tyrosine
moieties on proteins → leads to physiologic action
• Tyrosine-Kinase Associated Receptor (image at next page)
o e.g., GH, EPO
o Hormone binds to cell membrane receptor → noncovalent
association with Tyrosine Kinase (e.g., Janus family of receptor-
associated TK or JAK) → targets activators of transcription
(STAT) → new protein synthesis

© Topnotch Medical Board Prep


IP3/DAG 2nd MESSENGER SYSTEM
• Use by all hypothalamic hormones except CRH
• Mnemonic: “Phospholipase Ceeeee, PIPeeeeee, IPthreeee,
DAGeeee, Protein Kinase Ceeee”

© Topnotch Medical Board Prep

© Topnotch Medical Board Prep


CATALYTIC RECEPTOR MECHANISM
• Hormone cell membrane receptors are associated with enzymatic
activity on the intracellular side of the cell membrane
• Guanylyl Cyclase
© Topnotch Medical Board Prep
o e.g., in ANP, BNP, EDRF and NO
o Hormone binds to cell membrane receptor → Guanylyl cyclase
activated → coverts GTP to cGMP (acts as second messenger)
STEROIDS HORMONE AND THYROID HORMONE MECHANISM
• (+) penetration of cell membrane and synthesis of new proteins
STEROID HORMONES Lipid soluble →
CYTOPLASMIC receptor Cortisol
Cholesterol derivative Act on INTRACELLULAR receptors →
THYROID HORMONES Initiate gene transcription → Aldosterone, testosterone, Progesterone,
NUCLEAR receptor
Tyrosine derivative CREATE new proteins Estrogen, Vitamin D, T3 / T4
ADH (V2), angiotensin II
Activates PKA à (epithelial cells), catecholamines
ɑs (Gs) Activates AC ↑cAMP phosphorylation of (ß1 and ß2), ACTH, LH, FSH, TSH,
enzymes HCG, MSH, CRH, calcitonin, PTH,
secretin, somatostatin, glucagon
Inhibits PKA à
G protein
decreased
coupled ɑi (Gi) Inhibits AC ↓cAMP
phosphorylation of
catecholamines (ɑ2)
receptors
water soluble à enzymes
(GPCR)
closes GTP-
Activates cGMP
act on CELL ɑt (transducin) PDE
↓cGMP dependent ion retinal transducin
PROTEIN MEMBRANE channels
HORMONES receptors à ADH (V1), angiotensin II (vascular
PIP2 à IP3 à Ca release
ɑq (Gq) Activates PLC
IP3 + DAG DAG à activates PKC
smooth muscles), catecholamines
MODIFY existing (ɑ1), GnRH, TRH, GHRH, oxytocin
proteins Activates PKG à
Cell surface GC Activates GC ↑cGMP phosphorylation of ANP, NO, EDRF
enzymes
Enzyme- Serine/Threonine Phosphorylates Initiates gene
Smad signaling TGF-ß
linked kinase (RS/TK) RS/TK transcription
receptors Tyrosine kinase Phosphorylates Initiates gene NGF, EGF, PDGF, IGF-1, prolactin,
MAPK cascade
(RTK) RTK transcription leptin, insulin
Tyrosine- No intrinsic Src and JAK/STAT Initiates gene
EPO, interferons, cytokines, GH
associated kinase catalytic activity proteins transcription
Contributed by Jake Bryan Cortez, MD

© Topnotch Medical Board Prep


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✔GUIDE QUESTION SPECIAL NOTES ON ANTERIOR PITUITARY HORMONES
Which of the following hormones acts on its target tissues by a steroid • If the pituitary stalk is damaged, all anterior pituitary hormones
hormone mechanism of action? will be decreased EXCEPT: Prolactin
(A) Thyroid hormone
(B) Parathyroid hormone (PTH)
• Top 2 cells of the Anterior Pituitary: Somatotropes (40%) and
(C) Antidiuretic hormone (ADH) on the collecting duct Corticotropes (20%)
(D) β1 adrenergic agonists • 3 Families of Hormones of the Anterior Pituitary
(E) Glucagon From Physiology BRS, 6 Ed th o TSH, LH, FSH have the same alpha unit, unique beta unit
Again, even if thyroid hormone is made from the amino acid tyrosine, it § Members of the glycoprotein hormone family: FSH, LH, TSH, hCG
is lipid-soluble and will have a MOA similar to steroid hormones. o MSH, ACTH, Beta-Lipotropin, Beta-Endorphin (derived from POMC)
Dr. Banzuela
Which of the following hormones acts by an inositol 1,4,5-triphosphate
o GH, Prolactin, HPL (homologous)
(IP3)–Ca2+ mechanism of action? ✔GUIDE QUESTION
(A) 1,25-Dihydroxycholecalciferol Which of the following substances is derived from proopiomelanocortin
(B) Progesterone (POMC)?
(C) Insulin (A) Adrenocorticotropic hormone (ACTH)
(D) Parathyroid hormone (PTH) (B) Follicle-stimulating hormone (FSH)
(E) Gonadotropin-releasing hormone (GnRH). From Physiology BRS, 6 Ed th
(C) Melatonin
Again, all hypothalamic hormones except CRH utilize IP3-DAG. (D) Cortisol
Dr. Banzuela
(E) Dehydroepiandrosterone From Physiology BRS, 6 Ed
th

Secretion of the Hypothalamus include the following: CRH, GnRH,


Nooks and crannies: do not forget your POMC derivatives: MSH, ACTH,
Dopamine, Somatostatin, GHRH, TRH (oxytocin and vasopressin are
Endorphin and metenkephalin
synthesized in the hypothalamus, but STORED and SECRETED by the
posterior pituitary) Effect of panhypopituitarism: lack of one or multiple hormones from the
Dr. Banzuela pituitary gland. Manifestations include growth problems (children),
obesity (adults), bradycardia, hypoglycemia, hypotension, fatigue,
reproductive problems
7.3 PITUITARY GLAND Dr. Banzuela
PITUITARY GLAND
• Anterior Pituitary GROWTH HORMONE (GH)
o Derived from oral ectoderm (Rathke Pouch) • Has both catabolic and anabolic effects
o Basophilic Cells: • Released in pulsatile fashion every 2 hours
§ FSH, LH, ACTH, TSH, MSH • Nocturnal peak: 1 hour after Stage 3 or 4 Sleep
§ Mnemonic: BFLAT Major • Growth is due to interplay of GH, Thyroid Hormone, Androgens,
o Acidophilic Cells: Estrogens, Glucocorticoid, Insulin
§ GH, Prolactin o Inactive anterior pituitary (hypopituitarism) will decrease
• Posterior Pituitary GH which can lead to stunted growth
o Derived from neural ectoderm (neural outgrowth of • GH receptor requires dimerization to exert its effect
Hypothalamus) • GH activates: JAK2-STAT Pathway
o Pituicytes store and secrete: INDIRECT ACTIONS
§ Vasopressin (ADH), Oxytocin DIRECT ACTIONS
(VIA IGF-1)
Take note however that vasopressin and oxytocin are synthesized by the
nerve cell bodies in the supraoptic and paraventricular nuclei, respectively. • ↑ Plasma Glucose • ↑ Bone Length and
Dr. Banzuela (diabetogenic) Thickness (pubertal growth
• ↑ protein deposition and spurt)
lean body mass • ↑ protein synthesis in
• ↑ Lipolysis muscles and other organs
• ↑ IGF-1 and ↑ lean body mass
• Anti-aging effects • ↑ organ size
The indirect effects of GH (via IGF-1) is more powerful. IGF-1 is the one that
actually makes you grow and not GH – via an increase in both bone length
and thickness. Remember the 2nd messenger of IGF-1: tyrosine kinase.
Dr. Banzuela
Regulation of GH Secretion
© Topnotch Medical Board Prep
FACTORS INCREASING GH FACTORS DECREASING GH
Be careful with Prolactin vs. Oxytocin. Prolactin increases milk PRODUCTION. SECRETION SECRETION
It comes from the anterior pituitary. Oxytocin increases milk SECRETION. It • Starvation • Hyperglycemia
comes from the anterior hypothalamus (mainly the paraventricular nuclei) and • Hypoglycemia • High fatty acid levels
only stored and secreted in the posterior pituitary. Vasopressin is also
• Low fatty acid levels • Aging
synthesized in the anterior hypothalamus (mainly the supraoptic nuclei) and
only stored and secreted in the posterior pituitary. • Exercise • Obesity
Dr. Banzuela • Excitement • Somatostatin
ANTERIOR PITUITARY HORMONES • Trauma • Exogenous GH
ANTERIOR • Testosterone • Somatomedins (IGF)
HYPOTHALAMIC TARGET ORGAN TARGET
PITUITARY
HORMONE HORMONE ORGAN • Estrogen
HORMONE
Liver,
• GHRH
muscle, • Deep sleep
GHRH (+) GH IGF-1 • Secretion requires normal plasma levels of Thyroid Hormones
bone,
Somatostatin (-) (Somatotropin) (Somatomedin) Remember the table above – factors that increase or decrease GH. GH for
kidney,
etc. example is inhibited by Somatostatin and Somatomedin.
Dr. Banzuela
Thyroid
TRH (+) TSH T3, T4 ✔GUIDE QUESTION
gland
GC (main), Which of the following inhibits the secretion of growth hormone by the
along with MC Adrenal anterior pituitary?
CRH (+) ACTH (A) Sleep (D) Somatomedins
and weak Cortex
(B) Stress (E) Starvation
androgens From Physiology BRS, 6 Ed
(C) Puberty th

Estrogen,
GnRH (+) FSH, LH Progesterone,
GH Pathophysiology
Gonads
Testosterone • GH Deficiency:
PIH/ Dopamine o Growth retardation, short stature, mild obesity, delayed
Prolactin --- Breast puberty → dwarfism (in children)
(-)
o Causes: lack of anterior pituitary GH, hypothalamic dysfunction
What happens if GnRH is given in continuous infusion instead of in pulses?
(↓ GHRH), failure to generate IGF in liver, growth hormone
A: inhibition of FSH and LH
Dr. Banzuela receptor deficiency
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• GH Excess: OXYTOCIN
o Gigantism: symmetrical bone growth, occurs before closure of • Secreted by Hypothalamic Paraventricular Nuclei
epiphyses
• Actions:
o Acromegaly: asymmetrical bone growth, occurs after closure
o Milk ejection (contraction of myoepithelial cells)
of epiphyses
o Uterine contraction
Gigantism, acromegaly and Cushing Syndrome can all lead to glucose § basis for Nipple Stimulation
intolerance and diabetes because both GH and Cortisol can increase • Stimuli:
plasma glucose (they are diabetogenic hormones along with Epi and
o Suckling of the breast
Glucagon)
Dr. Banzuela o Cervical dilation
o Orgasm
PROLACTIN o Sight, sound, smell of infant
• Stimulates milk production (lactogenesis) Wag kalimutan mga stimuli for oxytocin nakasulat sa taas.
Dr. Banzuela
o Synthesis of lactose, casein, lipids
• Inhibits ovulation (females) or spermatogenesis (males) by ✔GUIDE QUESTION
INHIBITING GnRH Secretion of oxytocin is increased by
(A) milk ejection
• together with estrogen and progesterone, stimulates breast (B) dilation of the cervix
development during puberty and pregnancy (C) increased prolactin levels
Lactation amenorrhea in the first 6 months after delivery with regular (D) increased extracellular fluid (ECF) volume
breastfeeding is caused by prolactin inhibiting GnRH, preventing the LH (E) increased serum osmolarity From Physiology BRS, 6 Ed th

surge from occurring. Which of the following hormones originates in the anterior pituitary?
Dr. Banzuela (A) Dopamine
Regulation of Prolactin Secretion (B) Growth hormone–releasing hormone (GHRH)
FACTORS INCREASING FACTORS DECREASING (C) Somatostatin
PROLACTIN SECRETION PROLACTIN SECRETION (D) Gonadotropin-releasing hormone (GnRH)
• Estrogen (pregnancy) • Dopamine (E) Thyroid-stimulating hormone (TSH)
From Physiology BRS, 6th Ed
• Breast feeding • Bromocriptine (dopamine
• Sleep agonist)
• Stress • Somatostatin 7.4 THYROID GLAND
• TRH • Prolactin (via negative • Thyroid Follicular Epithelial Cells
• Dopamine antagonists feedback) o Synthesize thyroglobulin and thyroid hormone
§ Remember: Thyroglobulin is NOT the same as Thyroxine-
✔GUIDE QUESTION Binding Globulin (TBG)
A 38-year-old man who has galactorrhea is found to have a prolactinoma. His - High or Low Levels of TBG is associated with
physician treats him with bromocriptine, which eliminates the galactorrhea. EUTHYROIDISM; it has no effect on thyroid hormone
The basis for the therapeutic action of bromocriptine is that it function
(A) antagonizes the action of prolactin on the breast Therefore, high TBG does not affect the metabolic rate as much as TRH,
(B) enhances the action of prolactin on the breast TSH and Thyroid hormone
(C) inhibits prolactin release from the anterior pituitary Dr. Banzuela
(D) inhibits prolactin release from the hypothalamus o Thyroid hormone can be stored for 3 months in the thyroid
(E) enhances the action of dopamine on the anterior pituitary follicular lumen
From Physiology BRS, 6th Ed
o Thyroid hormone receptor is a heterodimer with retinoid X
receptor
POSTERIOR PITUITARY HORMONE: VASOPRESSIN
• Thyroid Parafollicular Cells (C Cells)
• a.k.a. Anti-Diuretic Hormone (ADH) or Arginine Vasopressin o Secrete calcitonin
(AVP)
• Synthesized by Hypothalamic Supraoptic Nuclei
• Responds to ECF changes detected by osmoreceptors in the
organum vasculosum (anteroventral wall 3rd ventricle)
• Stimulus: ↑ plasma osmolarity (most potent), ↓ blood pressure,
↓ blood volume
• Acts on:
ADH 2ND
EFFECT
RECEPTOR MESSENGER
V1
IP3/DAG vasoconstriction of arterioles
Receptors
V2 insertion of AQP-2 in the late distal
cAMP
Receptors tubule and collecting ducts
Mnemonic: V1 – think of 1 blood vessel. V2 – think of your 2 kidneys. © Topnotch Medical Board Prep
Dr. Banzuela
Don’t get confused please:
Regulation of ADH Secretion 1. Chief Cells of the Parathyroid Gland: produces PTH
FACTORS INCREASING ADH FACTORS DECREASING ADH 2. C cells of the Thyroid Gland: produces Calcitonin
SECRETION SECRETION Are TSH, T3, T4, TRH were secreted from the thyroid alone or with the help
• ↑ serum osmolarity • ↓ serum osmolarity of other organs? - TRH is secreted by the hypothalamus. TSH is secreted by
• Volume contraction • Ethanol the pituitary. T4 and T3 are secreted by the thyroid gland. Both
hypothalamus and pituitary affect the thyroid gland secrete T4 and T3.
• Pain • α-agonists Dr. Banzuela
• Nausea • ANP Listen to the audio recording as you read the next section on thyroid
• Hypoglycemia hormone synthesis and secretion:
• Nicotine, opiates,
antineoplastic agents THYROID HORMONE SYNTHESIS
AND SECRETION
Drug that is a vasopressin analog: DDVAP (1-desamino-8D-arginine
https://qrs.ly/8hebjlm
vasopressin) or Desmopressin
Dr. Banzuela
Dr. Banzuela

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This handout is only valid for October 2023 PLE batch. This will be rendered obsolete for the next batch since we update our handouts regularly.
STEPS IN THYROID HORMONE SYNTHESIS AND SECRETION
• Each step in thyroid hormone synthesis is stimulated by TSH
STEP EVENT SITE ENZYME
1 Synthesis of Thyroglobulin (TG) and extrusion into follicular lumen RER, Golgi Apparatus -
Na+-I- symporter (NIS), a form of secondary active transport, causes Iodide
2 Basal Membrane -
(I-) uptake
3 Transport of I- to follicular lumen. (using Pendrin) Oxidation of I- to I2 Apical / Luminal Membrane Peroxidase
4 Organification of I2 and Tyrosine to MIT and DIT Apical / Luminal Membrane Peroxidase
5 Coupling: MIT + DIT → T3 and DIT + DIT → T4 Apical / Luminal Membrane Peroxidase
6 Endocytosis of iodinated TG due to TSH Apical / Luminal Membrane -
7 Hydrolysis of T3 and T4 → T4 and T4 enter circulation Lysosomes Proteases
8 Deiodination of residual MIT, DIT & recycling of I- & tyrosine Intracellular Deiodinase

© Topnotch Medical Board Prep

Please memorize also the sites inside the cell where each step occurs (seen
in the table above)
© Topnotch Medical Board Prep Dr. Banzuela

THYROID HORMONE CONDITION DESCRIPTION


T4 T3 • ↓ BMR, weight gain, cold intolerance,
3,5,3',5'- 3,5,3'- lethargy, whole-body myxedema, mental
Other name and grown retardation (in congenital
tetraiodothyronine triiodothyronine Hypothyroidism
Percentage hypothyroidism)
93% 7% • Hypothyroidism causes cholesterol levels
synthesized
to INCREASE
Half-life More (6 days) Less (1 day)
• Ingestion of large amount of iodine
Affinity for Wolff-Chaikoff
reduces T3 and T4.
binding plasma More Less Effect
• Used as treatment of hyperthyroidism.
protein
• Hyperthyroidism following small
Binding to Less (10% of the More (90% of the increased ingestion of iodine typically in
nuclear receptor receptors) receptors) Jod-Basedow
patients with endemic goiter (due to iodine
Onset of action 4x slower (2 days) 4x faster (12 hours) Phenomenon
deficiency) who relocate to iodine-rich
EFFECTS OF THYROID HORMONES areas.
• ↑ O2 consumption and Basal Metabolic Rate (BMR) Exophthalmos is the protrusion of the eyeball caused by fat and
o ↑ mitochondria and Na-K-ATPase pump activity glycosaminoglycans (GAGS) behind the eyeball. It is seen in Graves disease.
• Stimulates carbohydrate, fat and protein metabolism Exophthalmos is specific to Graves disease and not to hyperthyroidism –
o ↑ glucose uptake, gluconeogenesis, glycogenolysis remember that not all cases of hyperthyroidism is Graves, therefore not all
cases of hyperthyroidism will have exophthalmos.
o ↓ cholesterol, phospholipids and triglycerides but ↑ fatty acids
Basal Metabolic Rate (BMR) – makes up 60-70% of calories burned per day.
§ ↑ cholesterol secretion to bile & number of liver LDL receptors To compute for BMR base on revised Harris-Benedict Equation:
o ↑ protein synthesis needed for Growth 𝑀𝑒𝑛: 𝐵𝑀𝑅 = 88.362 + M13.397 × 𝑤𝑡!" S + (4.799 × ℎ𝑡#$ ) − (5.677 × 𝑎𝑔𝑒%&' )
• Works together with GH and IGF-1 for bone formation and bone 𝑊𝑜𝑚𝑒𝑛: 𝐵𝑀𝑅 = 447.593 + M9.247 × 𝑤𝑡!" S + (3.098 × ℎ𝑡#$ ) − (4.330 × 𝑎𝑔𝑒%&' )
maturation Dr. Banzuela

• ↑ requirements for vitamins ✔GUIDE QUESTIONS


• ↑ blood flow, Cardiac Output, Heart Rate, Heart Strength (Normal / Which of the following would be expected in a patient with Graves’
↑ BP, wide pulse pressure due to ↓TPR) disease?
o (+) chronotropic, inotropic and lusitropic effect (A) Cold sensitivity
o ↑ B1 receptors, myosin, SR Ca-ATPase in the heart (B) Weight gain
(C) Decreased O2 consumption
• ↑ respiration (D) Decreased cardiac output
• ↑ gastrointestinal motility (E) Increased triiodothyronine (T3) levels
• ↑ cerebration in adults From Physiology BRS, 6th Ed

• For CNS maturation in the perinatal period Blood levels of which of the following substances is decreased in Graves
disease?
• ↑ muscle vigor = fine Muscle Tremors (A) Triiodothyronine (T3)
• ↑ risk for somnolence (B) Thyroxine (T4)
• Needed for proper sexual function (C) Diiodotyrosine (DIT)
o Loss may cause loss of libido, impotence, menstrual changes (D) Thyroid-stimulating hormone (TSH)
(E) Iodide (I–) From Physiology BRS, 6 Ed th

PATHOPHYSIOLOGY OF THYROID HORMONE Propylthiouracil can be used to reduce the synthesis of thyroid hormones
CONDITION DESCRIPTION in hyperthyroidism because it inhibits oxidation of
• ↑ Basal Metabolic Rate (BMR), ↑ cardiac (A) Triiodothyronine (T3)
output, weight loss, tremors, heat (B) Thyroxine (T4)
intolerance, pre-tibial myxedema, (C) Diiodotyrosine (DIT)
exophthalmos (in Graves Disease) (D) Thyroid-stimulating hormone (TSH)
Hyperthyroidism • Hyperthyroidism presents with 2-3x larger (E) Iodide (I–) From Physiology BRS, 6 Ed th

thyroid, hyperplasia and infolding of the


follicular cell lining into the follicles
decreasing the cross-sectional area
occupied by the colloid
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7.5 ADRENAL CORTEX AND MEDULLA Hormone Half-Life


Listen to this audio recording while reading the next section on adrenal
Aldosterone 20 minutes
hormones: Corticosterone 60-90 minutes
DHEA 7-22 hours
Epinephrine 2 minutes
ADRENAL HORMONES Norepinephrine 2 minutes
https://qrs.ly/x9ebjn5 Renin 15 minutes
MNEMONICS ADRENAL CORTEX
Dr. Banzuela
G-F-R
ADRENAL HORMONES
• Adrenal Cortex Glomerulosa, Fasciculata, Reticularis
LAYER HORMONE(S) SECRETED “The deeper you go, the sweeter it gets.”
Zona Glomerulosa Aldosterone (mineralocorticoid) “Salt, Sweet, Sex”
Cortisol, Corticosterone Aldosterone, Cortisol, Weak Sex Hormones
Zona Fasciculata
(glucocorticoids) ✔GUIDE QUESTION
De-hydro-epi-androsterone (DHEA) Selective destruction of the zona glomerulosa of the adrenal cortex
Zona Reticularis would produce a deficiency of which hormone?
Androstenedione (weak androgens)
• Adrenal Medulla (A) Aldosterone (D) Dehydroepiandrosterone
(B) Androstenedione (E) Testosterone
o Epinephrine: 80% From Physiology BRS, 6th Ed
(C) Cortisol
o Norepinephrine: 20% Which step in steroid hormone biosynthesis is stimulated by
adrenocorticotropic hormone (ACTH)?
(A) Cholesterol → pregnenolone
(B) Progesterone → 11-deoxycorticosterone
(C) 17-Hydroxypregnenolone → dehydroepiandrosterone
(D) Testosterone → estradiol
(E) Testosterone → dihydrotestosterone
From Physiology BRS, 6th Ed
Which step in steroid hormone biosynthesis, if inhibited, blocks the
production of all androgenic compounds but does not block the
production of glucocorticoids?
(A) Cholesterol → pregnenolone
(B) Progesterone → 11-deoxycorticosterone
(C) 17-Hydroxypregnenolone → dehydroepiandrosterone
(D) Testosterone → estradiol
(E) Testosterone → dihydrotestosterone
From Physiology BRS, 6th Ed

Look at ACTH and Angiotensin II at the image below. Remember: ACTH


© Topnotch Medical Board Prep
stimulates desmolase. It will therefore increase all adrenocortical
hormones. Remember also this: Angiotensin II stimulates aldosterone
synthase. It will therefore increase aldosterone.
Dr. Banzuela

© Topnotch Medical Board Prep

ALDOSTERONE o ↑H+ Secretion in the kidneys (maybe triggered by


hyperkalemia)
• Under tonic control by ACTH but separately regulated by RAAS
and Serum Potassium (hyperkalemia increases aldosterone • Aldosterone increases transport of Epithelial Na Channels
secretion to restore K levels to normal) (ENaCs) from cytoplasm to cell membrane
• Effects • Mole for mole, Aldosterone has the greatest effect on Na+
o ↑ Na+ Reabsorption in the kidneys, sweat glands, salivary excretion
glands and colon o Mole for mole, ADH has the greatest effect on plasma
§ Best describes colonic function: Absorption of Na+ in the osmolality (BE CAREFUL NOT TO CONFUSE ALDOSTERONE VS.
colon is under hormonal control by aldosterone ADH!!!)
o ↑ K+ Secretion in the kidneys and colon
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✔GUIDE QUESTION CONDITION CLINICAL FEATURES
Which of the following causes increased aldosterone secretion? 17-Alpha • Lack of pubic and axillary hair in women, SSx of
(A) Decreased blood volume Hydroxylase glucocorticoid deficiency and mineralocorticoid
(B) Administration of an inhibitor of angiotensin-converting enzyme deficiency excess
(ACE)
(C) Hyperosmolarity ✔GUIDE QUESTIONS
(D) Hypokalemia From Physiology BRS, 6 Ed th A 46-year-old woman has hirsutism, hyperglycemia, obesity, muscle
wasting, and increased circulating levels of adrenocorticotropic hormone
In 21B-hydroxylase deficiency, which hormone is elevated? (ACTH). The most likely cause of her symptoms is
A: Weak Androgens (Androstenedione) (A) primary adrenocortical insufficiency (Addison’s disease)
Dr. Banzuela
(B) pheochromocytoma
CORTISOL (C) primary overproduction of ACTH (Cushing disease)
(D) treatment with exogenous glucocorticoids
• Essential for response to stress (E) hypophysectomy From Physiology BRS, 6 Ed th

• Oscillates with circadian rhythm Increased adrenocorticotropic hormone (ACTH) secretion would be
o Highest levels: before waking up (approx. 8am) expected in patients
o Lowest levels: in the evening (approx. midnight) (A) with chronic adrenocortical insufficiency (Addison disease)
o Rise sharply during sleep, peak soon after awakening, sink to a (B) with primary adrenocortical hyperplasia
low level 12 hours later: Cortisol (C) who are receiving glucocorticoid for immunosuppression after a
• Carbohydrate Effects renal transplant
(D) with elevated levels of angiotensin II From Physiology BRS, 6 Ed
o Stimulates gluconeogenesis
th

o ↑ protein catabolism in muscles 7.6 ENDOCRINE PANCREAS


o ↓ glucose utilization and insulin sensitivity of adipose tissue
ISLETS OF LANGERHANS: ENDOCRINE PANCREAS
• Protein Effects
CELL TYPE PERCENTAGE AREA SECRETION
o ↓ cellular proteins (except liver)
o ↑ blood amino acids Beta Cells 60% (in Central Islet) Insulin and Amylin
o ↑ liver and plasma proteins
Alpha Cells 25% (in Outer Rim) Glucagon
• Fat Effects
o ↑ lipolysis Delta Cells 10% (Intermixed) Somatostatin
§ Moon Face and Buffalo hump: due to increase appetite, and F Cell / PP Pancreatic
5%
fat being generated in some tissues faster than it is being Cell Polypeptide
metabolized Insulin – utilizes tyrosine kinase as second messenger. Comes from Beta Cells.
• Anti-inflammatory Effects Glucagon – utilizes cAMP as second messenger. Comes from Alpha Cells.
Dr. Banzuela
o induces synthesis of lipocortin which inhibits Phospholipase A2
needed for PG and LT synthesis GLUCAGON
o Stabilizes lysosomal membranes
• Main Stimulus: Low Blood Glucose
o Decreases migration and phagocytosis of WBCs
• 2nd Messenger: cAMP
o Suppression of T-lymphocytes
• Actions
o ↓ IL-1, IL-2
o ↑ Blood Glucose
o ↑ resolution of inflammation
§ ↑ glycogenolysis
o Blocks inflammatory response to allergies
§ ↑ gluconeogenesis
o ↓ eosinophils and lymphocytes
o ↑ Blood Fatty acid and Ketoacids
o Inhibits histamine and serotonin release
o ↑ Urea production (due to ↑ amino acids)
o ↑ RBCs (unknown MOA)
o ↑ Insulin
• Anti-inflammatory effects require HIGH LEVELS of circulating
glucocorticoids
• Basis for anti-inflammatory effect of exogenous glucocorticoids:
inhibition of activation factor-KB (NF-KB)
• Maintenance of Vascular Responsiveness to Catecholamines
o Upregulates 𝛼1 receptors on arterioles, increasing
Epinephrine’s vasoconstrictor effects →→ Increases BP
• Inhibits Bone Formation
o ↓ synthesis of Type I collagen, decreasing formation of new bone
by osteoclast, and decreasing calcium absorption
• Increases GFR
o Vasodilation of afferent arterioles
• CNS Effects
o ↓ REM sleep, ↑ slow-wave sleep, ↑ waking time
ADRENAL DISORDERS © Topnotch Medical Board Prep

CONDITION CLINICAL FEATURES PANCREATIC SOMATOSTATIN


• Low Aldosterone causes: hypotension, • Inhibits both glucagon and insulin to modulate their effects
hyperkalemia, metabolic acidosis • Inhibits all GI hormones
• Low Cortisol causes: hypoglycemia, anorexia,
• Stimulated by all types of nutrients
weight loss, nausea, vomiting, weakness
• Decreases motility of stomach, duodenum and gallbladder
Addison • Low weak androgen causes: decreased pubic
Disease and axillary hair in women • Decreases both absorption and secretion in the GI tract
*take note: there’s also GI somatostatin and hypothalamic somatostatin
• Hyperpigmentation (due to increased POMC
secretion as response to low levels of adrenal
hormones; recall that POMC has MSH – which causes INSULIN
stimulation of melanocytes to secrete melanin) • Main Stimulus: High Blood Glucose
• Hyperglycemia, muscle wasting, central obesity, • 2nd messenger: Tyrosine Kinase Receptor
Cushing
round face, supraclavicular fat, buffalo hump, • Half-Life: 6 minutes (degraded by liver insulinase)
Syndrome /
osteoporosis, striae, virilization and menstrual • Connecting Peptide (C Peptide): packaged and secreted with
Disease
disorders in women, hypertension
endogenous insulin
Conn • Hypertension, hypokalemia, metabolic alkalosis,
• stimulates/targets the following organs for glucose uptake:
Syndrome decreased renin
Liver(hepatic), skeletal muscle, adipose (NOT brain)
• Virilization in women, pseudo-precocious
21-Beta
puberty in men, early acceleration of linear
Hydroxylase
growth, SSx of glucocorticoid and
deficiency
mineralocorticoid deficiency

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• Causes high LDL, high VLDL, high TG, low HDL in DM Type 2:
decreased lipoprotein lipase activity due to insufficient insulin
action in adipose
• Fluid to give for DKA: NSS
Hypoglycemia
• Counter-regulatory hormones (Diabetogenic Hormones)
o Epinephrine (main)
o Glucagon (main)
o Cortisol (supplemental)
© Topnotch Medical Board Prep o Growth Hormone (Supplemental)
✔GUIDE QUESTION • Combined medullary insufficiency (decreased Epinephrine)
Which of the following pancreatic secretions has a receptor with four
and Glucagon deficiency will cause delay in response to
subunits, two of which have tyrosine kinase activity?
(A) Insulin (C) Somatostatin
hypoglycemia
(B) Glucagon (D) Pancreatic lipase • Meal rich in proteins containing amino acids that causes insulin
From Physiology BRS, 6th Ed secretion → also increases glucagon secretion to prevent
INSULIN VS. GLUCAGON hypoglycemia
HORMONE STIMULI EFFECTS • Physiologic secretion of growth hormone is increased by:
↑ Plasma Glucose ↑ Cellular Glucose uptake hypoglycemia
↑ Plasma Amino ↓ Glycogenolysis,
Acids (AA) gluconeogenesis 7.7 CALCIUM METABOLISM
↑ Plasma Fatty BONE
↑ Protein synthesis
Acids (FA) • Organic Matrix (30%)
Insulin
Glucagon ↑ Lipogenesis o Ground Substances
GIP (via oral § ECF + Chondroitin Sulfate + Hyaluronic Acid
↑ K+ uptake
glucose) § Gelatinous medium
GH - o Collagen Fibers
Cortisol - § 95% of Organic Matrix
↑ Glycogenolysis and § for Tensile Strength
↓ Plasma Glucose • Bone Salts (70%)
gluconeogenesis
↑ lipolysis and ketone body o Ca10(PO4)6(OH)2
Glucagon ↑ Plasma AA § for Compressional Strength
formation
CCK - Why shouldn’t the bone be made up of 100% bone salts? Because if the bone
NE, Epinephrine, ACh is made up entirely of bone salts, it would be hard but breakable like marble.
You need the collagen for tensile strength, so it won’t be easy to break.
Insulin for well-fed state pathways. Glucagon for fasting state pathways.
Example of a “cross-over trivial” question more appropriate for other subjects
Occurs in insulin deficiency: INCREASED gluconeogenesis, and unlikely to be covered by this physiology handout/lecture: Fluid-filled
glycogenolysis, lipolysis, ketogenesis, proteolysis. DECREASED swelling that develops at the back of the knee caused by osteoarthritis or
glycolysis, glycogen synthesis, protein synthesis meniscal tear? A: Baker Cyst (also called POPLITEAL cyst)
Dr. Banzuela Dr. Banzuela

DIABETIC KETOACIDOSIS BONE REMODELING


• Hyperglycemia: Due to insulin deficiency BONE DEPOSITION BONE RESORPTION
• Hypotension: due to high filtered load of glucose acting as • Osteoblast • Osteoclasts
osmotic diuretic decreasing intravascular volume • Secrete Collagen & Ground • Secrete Lysosomal
• High Anion Gap Metabolic Acidosis: due to overproduction of Substance where calcium enzymes, Citric Acid and
ketone bodies. (+) Kussmaul respiration seen precipitates Lactic Acid
• Hyperkalemia: due to insulin deficiency
• Insulin given to DKA leads to
o Reduction in compensatory hyperventilation (resolution of
acidosis and improvement of serum bicarbonate due to IV
insulin infusion)
✔GUIDE QUESTION
A 39-year-old man with untreated diabetes mellitus type I is brought to
the emergency room. An injection of insulin would be expected to cause
an increase in his
(A) urine glucose concentration (D) blood pH
(B) blood glucose concentration (E) breathing rate
(C) blood K+ concentration
From Physiology BRS, 6th Ed
Patient here is having diabetic ketoacidosis (plasma pH<7.35). Insulin BONE REMODELING PROCESS
© Topnotch Medical Board Prep
would address this ketoacidosis and increase his plasma pH
Dr. Banzuela BODY CALCIUM
DIABETES MELLITUS • 99% as hydroxyapatite in Bone
FEATURE TYPE 1 TYPE 2 • 0.1% in the interstitium
Age of onset Usually < 30 y/o Usually > 40 y/o • <0.5% in plasma
o 41% as protein-bound calcium
Body mass Low to normal Obese
o 9% as anion-bound calcium
Plasma insulin Low or absent Normal to high initially
o 50% as Free and ionized calcium (5mg/dL): biologically
Coxsackie virus, Insulin resistance (this
active
Pathophysiology Anti-islet cell can be decreased using
autoantibodies weight reduction) Functions of free, ionized Calcium
A: MUSCLE CONTRACTION, blood clotting, maintenance of blood vessel
Plasma High; can be High; resistant to
integrity, nerve conduction
glucagon suppressed suppression Dr. Banzuela
Plasma glucose ↑ ↑ CALCIUM METABOLISM
Insulin • To maintain Ca2+ balance, net intestinal absorption (calcium
Normal Reduced
sensitivity intake) must be balanced by urinary excretion (calcium
Crisis DKA HHS excretion)
Weight loss, • Positive Calcium Balance
thiazolidinediones, o Calcium Intake > Calcium Excretion
Therapy Insulin metformin, sulfonylureas,
o e.g., in growing children
insulin
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• Negative Calcium Balance ✔GUIDE QUESTION
o Calcium Intake < Calcium Excretion Which of the following decreases the conversion of 25-
o e.g., in pregnant or lactating women hydroxycholecalciferol to 1,25-dihydroxycholecalciferol?
(A) A diet low in Ca2+ (D) Hypophosphatemia
(B) Hypocalcemia (E) Chronic renal failure
VITAMIN D From Physiology BRS, 6 Ed
(C) Hyperparathyroidism th

• Vitamin D is primarily absorbed by: simple diffusion


• ACTIVE Vitamin D: 1,25 dihydroxy-cholecalciferol (calcitriol) PTH
o Increases intestinal Ca2+ absorption via alteration in activity of • Secreted by: Chief Cells of the Parathyroid Gland
genes involved in calcium transport (Ca2+ ATPase) and • Stimulus: low plasma Ca2+
Calbindin o ↑ number and activity of osteoclasts
• INACTIVE Vitamin D: 24, 25 dihydroxy-cholecalciferol o ↑ plasma Ca2+
o Produced instead when there is Hypercalcemia • Also stimulated by hypomagnesemia
• Increases both plasma Ca++ and PO4- o Except hypomagnesemia caused by alcoholism
• 2nd Messenger: cAMP
• In hypoparathyroidism (e.g., secondary to parathyroidectomy):
o Low plasma Ca2+, High Plasma PO4-
o (+) neuromuscular excitability
o (+) Hypocalcemic tetany (Chvostek and Trousseau Sign)

CALCITONIN
• Secreted by: Parafollicular cells (C Cells) of the Thyroid Gland
• Stimulus: high plasma Ca2+
o Inhibits bone resorption
o ↓ number and activity of osteoclast
o ↓ plasma Ca2+
© Topnotch Medical Board Prep

• Delayed dentation, short stature, painful walking, bowing of legs Listen to this audio recording while reading the table of PTH vs. Vitamin D
below:
is caused by: decreased calcification of bone matrix (rickets)
Wag dedeadmahin ang inactive (storage) form of Vitamin D –
24,25(OH)2CC. Importante yan. If you have hypercalcemia, siya ang PTH VS. VITAMIN D
madami. Pag may hypocalcemia naman, dadami ang active form of https://qrs.ly/puebjnd
Vitamin D – 1,25(OH)2CC.
Dr. Banzuela

Dr. Banzuela

PTH Vitamin D Calcitonin


⬇ serum [Ca2+]
Stimulus for secretion ⬇ serum [Ca2+] ⬆ PTH ⬆ serum [Ca2+]
⬇ serum [Phosphate]
Action on
⬆ bone deposition at RDA levels
Bone ⬆ resorption ⬇ resorption
⬆ resorption at high toxic levels
⬇ PO4- reabsorption (⬆urinary cAMP) ⬆ PO4- reabsorption
Kidney --
⬆ Ca2+ reabsorption ⬆ Ca2+ reabsorption
No direct effect; indirect ⬆ Ca2+ absorption ⬆ Ca2+ reabsorption (calbindin D-28K)
Intestine --
via activation of Vitamin D ⬆ PO4- absorption
Overall effect on
Serum [Ca2+] ⬆ ⬆ ⬇
Serum [Phosphate] ⬇ ⬆ --
✔GUIDE QUESTIONS MALE EXTERNAL GENITALIA DEVELOPMENT
Which of the following results from the action of parathyroid hormone
(PTH) on the renal tubule?
(A) Inhibition of 1-alpha-hydroxylase
(B) Stimulation of Ca2+- reabsorption in the distal tubule
(C) Stimulation of phosphate reabsorption in the proximal tubule
(D) Interaction with receptors on the luminal membrane of the
proximal tubular cells
(E) Decreased urinary excretion of cyclic adenosine monophosphate
(cAMP) From Physiology BRS, 6 Ed th

A 41-year-old woman has hypocalcemia, hyperphosphatemia, and


decreased urinary phosphate excretion. Injection of parathyroid
hormone (PTH) causes an increase in urinary cyclic adenosine
monophosphate (cAMP). The most likely diagnosis is?
(A) primary hyperparathyroidism
(B) vitamin D intoxication
(C) vitamin D deficiency
(D) hypoparathyroidism after thyroid surgery
(E) pseudohypoparathyroidism From Physiology BRS, 6 Ed th

7.8 SEXUAL DIFFERENTIATION


SEXUAL DIFFERENTIATION
• Genetic Sex: determined by sex chromosomes
• Gonadal Sex: determined by presence of testes in males and
ovaries in females
• Phenotypic Sex: determine by characteristics of internal genital © Topnotch Medical Board Prep

tract and external genitalia There’s really no good mnemonic for the next table. You must do hard core
Key points: remember SRY gene and TDF. SRY gene is seen in the Y memorization for it – importante ‘yan
chromosome. SRY gene encodes for TDF. TDF is the protein that causes Dr. Banzuela

creation of testes. Mullerian inhibiting factor (MIF) causes degeneration


of the Mullerian ducts (female structures). Testosterone stimulate growth
of the Wolffian ducts (the one that develops into male genital tract).
Dr. Banzuela

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© Topnotch Medical Board Prep

BIPOTENTIAL 7.9 MALE REPRODUCTION


MALE FEMALE
STRUCTURE PHYSIOLOGIC ANATOMY OF MALE SEX ORGANS
GONADS STRUCTURE FUNCTION
REGRESSES OVARIES
(cortex) • Sperm production
GONADS Seminiferous • Full development and function of
TESTIS REGRESSES
(medulla) Tubules seminiferous tubules require
Epididymis, Vas androgens and FSH Ganong 25 23-1
WOLFFIAN th

Deferens, Seminal REGRESSES • For sperm STORAGE (minor


DUCT Epididymis
Vesicle contribution from vas deferens)
Fallopian tubes, • For propulsion of sperm during sex
MÜLLERIAN Vas Deferens
REGRESSES Uterus, Cervix, to the urethra
DUCT
Vagina (Upper 1/3) • Sperm nutrition (contains fructose,
Glans Penis, Seminal Vesicle
prostaglandins)
Corpus GENITAL Glans Clitoris,
• For semen alkalinity (using
cavernosum & TUBERCLE Vestibular Bulb
spermine); contains 5-alpha
spongiosum
reductase that converts testosterone
Penis (Ventral Prostate Gland to DHT
GENITAL FOLDS Labia minora
shaft)
• Neutralizes acidity of other fluids
GENITAL during ejaculation, enhancing
Scrotum, Labia majora
SWELLING fertility of sperm
Female urethra, Ejaculatory Duct -
Male urethra
lower vagina
Urethra -
Urethral &
UROGENITAL Urethral Glands,
Prostate gland Paraurethral
SINUS Bulbourethral • Supplies mucus for lubrication
glands of Skene
Glands
Bulbourethral Greater vestibular
glands of Cowper glands of Bartholin Sperm is produced in the seminiferous tubules, mature in the epididymis,
stored in the vas deferens, gets its nutrition (fructose) from seminal vesicle
and becomes alkaline in the prostate gland. Don’t forget these.
What do you tell a patient prior sperm analysis? A: Abstain sexual intercourse
3 days prior (Day 1- +intercourse Days 2-4- abstain Day 5- semenalysis)
Dr. Banzuela
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Take note that the Sertoli Cells can release both Androgen-Binding Protein
REMEMBER PATH OF SEMEN
and Inhibin. But FSH will only stimulate the Sertoli Cells to secrete
S eminiferous tubules (N othing) Androgen-Binding Protein (ABP) and not inhibin (inhibin decreases FSH
E pididymis U rethra levels). This ABP ensures a high testosterone supply for spermatogenesis.
V as deferens P enis LH meanwhile stimulates testosterone secretion from the Leydig Cells
E jaculatory ducts Dr. Banzuela

✔GUIDE QUESTIONS
SPECIAL NOTES ON MALE REPRODUCTIVE PHYSIOLOGY Which step in steroid hormone biosynthesis occurs in the accessory sex
• Testes temperature: 1-2°C cooler than core body target tissues of the male and is catalyzed by 5α-reductase?
o requires temperature lower than body temp: Spermatogenesis (A) Cholesterol → pregnenolone
• Activation of sperm in the female genital tract: capacitation (B) Progesterone → 11-deoxycorticosterone
• NTs used in erection: NO and Ach (C) 17-Hydroxypregnenolone → dehydroepiandrosterone
(D) Testosterone → estradiol
o Nitric Oxide synthase → ↑ NO → activates guanylyl cyclase →
(E) Testosterone → dihydrotestosterone. From Physiology BRS, 6th Ed
↑cGMP → potent vasodilator → Erection Which of the following functions of the Sertoli cells mediates negative
• Oligospermia (Low Sperm Count): <15 million sperms/mL feedback control of follicle-stimulating hormone (FSH) secretion?
• Vestigial remnant of 3rd eye; secretes melatonin involved in (A) Synthesis of inhibin
reproduction and sex drive: pineal gland (B) Synthesis of testosterone
o Circadian rhythm is controlled by: Suprachiasmatic Nuclei (C) Aromatization of testosterone
(SCN) of the Hypothalamus (in turn regulated by Pineal (D) Maintenance of the blood–testes barrier
Gland thru melatonin) • function of Sertoli Cells in the seminiferous tubules: Maintenance of
blood-testis barrier (Sertoli cells intimately associated with
• Sperm: viable for 1-5 days in the female genital tract (average of
developing spermatozoa) From Physiology BRS, 6 Ed th
3 days or 72 hours)
• Mechanism for prevention of polyspermy: cortical reaction that MNEMONICS MALE SEX HORMONES
modifies zona pellucida S-S-S
• Childhood: FSH and LH are at their lowest, FSH > LH FSH, Sertoli Cell, Sperm
• Puberty: FSH and LH increase, FSH < LH L-L-L
• Senescence: FSH and LH at their highest, FSH > LH LH, Leydig Cell, Libido Hormone (Testosterone)
• Weakest to strongest androgens: androstenedione, TESTOSTERONE DIHYDROTESTOSTERONE
testosterone, dihydrotestosterone (DHT) • Differentiation of epididymis, • Differentiation of penis,
• Forms of testosterone in the blood: vas deferens, & seminal vesicles scrotum, and prostate
o 60% bound to Sex-Hormone Biding Globulin (SHBG) • Descent of testes • Male hair pattern
o 38% bound to albumin • ↑ bone and muscle mass (e.g., • Male pattern baldness
o 2% as free testosterone broad shoulders) • Sebaceous gland activity
• ↑ BMR • Growth of prostate
• Pubertal growth spurt
• Epiphyseal closure
• Growth of penis & seminal
vesicles
• Deepening of voice
(enlargement of larynx)
• Spermatogenesis
• Negative feedback on anterior
pituitary
• Libido
✔GUIDE QUESTION
© Topnotch Medical Board Prep A 16-year-old, seemingly normal female is diagnosed with androgen
Sperm has 72 hours (3 days) to meet its reproductive destiny, the egg cell. insensitivity disorder. She has never had a menstrual cycle and is found
The egg cell has 24 hours to meet its reproductive destiny, the sperm cell. to have a blind- ending vagina; no uterus, cervix, or ovaries; a 46 XY
Male Pseudohermaphroditism may lack the enzyme 5 alpha-reductase. They genotype; and intra- abdominal testes. Her serum testosterone is
have 46XY, (+) testes, but ambiguous genitalia or complete female phenotype. elevated. Which of the following characteristics is caused by lack of
Female Pseudohermaphroditism may lack 21-Beta hydroxylase. They androgen receptors?
have 46XX karyotype, (+) ovaries but ambiguous external genitalia due to (A) 46 XY genotype (D) Lack of uterus and cervix
virilization caused by excessive weak androgens. (B) Testes (E) Lack of menstrual cycles
From Physiology BRS, 6 Ed
Term for a male without a testes from castration: Eunuch. (C) Elevated serum testosterone th

Dr. Banzuela

SPERMATOGENESIS

© Topnotch Medical Board Prep

© Topnotch Medical Board Prep

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STEPS: 7.10 FEMALE REPRODUCTION
1. Mitotic division of germ cell (Spermatogonia Type A) into ESTROGEN
spermatogonia Type A and B • Forms of Estrogen
2. Enlargement of spermatogonia type B or undergo mitosis to o Estrone: secreted by adrenal cortex and thecal cell
form spermatocytes.
o Estradiol: secreted by ovaries
3. 1st meiotic division: primary spermatocytes become
o Estriol: secreted by placenta
secondary spermatocytes (haploid).
• Aromatase
4. 2nd meiotic division: secondary spermatocytes becomes two
o Enzyme that catalyzes conversion of Androstenedione →
spermatids.
Estrone & Testosterone → Estradiol
5. Spermiogenesis: Spermatids change shape to become
o Needed for development of female (not male) secondary sex
spermatozoon.
characteristics
Step in Spermatogenesis where all 46 chromosomes replicate: Meiosis I.
Dr. Banzuela

© Topnotch Medical Board Prep


Listen to the audio recording below while looking at the diagram for the
MNEMONICS FORMS OF ESTROGEN
menstrual cycle:
EstraDIOL 2 pa lang kayo (wifey, hubby)
Main form of estrogen during the reproductive years
EsTRIOL: 3 na kayo (wifey, hubby, baby) MENSTRUAL CYCLE
Main form of estrogen during pregnancy https://qrs.ly/yiebjnk
EstrONE: 1 ka na lang (wifey na lang, deds na si hubby)
Main form of estrogen during post-menopausal years Difference in Estrogen vs Progesterone effects on the breasts: Estrogen:
ductile elements, fat deposition. Progesterone: glandular elements
PROGESTERONE
Typical physical characteristics of females: Wide hips, thighs converge at
• Secreted by the corpus luteum, placenta, adrenal cortex, testes
the knees, knee joints more angulated laterally
ESTROGEN EFFECTS Dr. Banzuela

• Produce cyclic changes in the vagina and endometrium


• cervical mucus becomes thinner, more alkaline and exhibit MENSTRUAL CYCLE
fernlike pattern upon drying
• Inhibits osteoclasts (protective against osteoporosis)
• Decreases serum cholesterol
• Increases libido
• stimulates growth of ovarian follicle, glandular epithelium of
endometrium, smooth muscle of uterus and uterine vascular
system
• stimulates ductal elements of the breast (progesterone stimulates
growth of glandular elements of the breasts)
• Maturation of uterus, fallopian tubes, cervix, and vagina
• Breast development
• Development of granulosa cells
• Up-regulation of estrogen, progesterone, and LH receptors
• Negative and positive feedback effects on FSH and LH secretion
• Maintenance of pregnancy
• Lowering of uterine threshold to contractile stimuli
• Stimulates prolactin secretion
• Blocks action of prolactin on breast
• Slightly increases BMR but causes fat deposition
• Creates soft skin
PROGESTERONE EFFECTS
• Increases endometrial glandular secretion
• Maintenance of secretory activity of uterus during luteal phase
© Topnotch Medical Board Prep
• Breast development
• Proper term: female monthly sexual cycle
• Negative feedback effects on FSH and LH secretion
• Normal length: 28 +/- 7 days
• Maintenance of pregnancy
• In a lifetime: occurs approximately 400x
• Raising uterine threshold to contractile stimuli during pregnancy
• Has 2 Phases
• Effect of HRT: Reduces the incidence of hot flashes (but may o Follicular Phase (Proliferative Phase)
increase risk of coronary artery disease, endometrial CA, breast § Estrogen predominates
CA, venous thromboembolism, gallbladder disease) o Luteal Phase (Secretory Phase)
§ Progesterone predominates

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FOLLICULAR PHASE (DAY 0-14) • First trimester: HCG-stimulated corpus luteum is responsible
• Primordial follicle develops to Graafian stage, with atresia of for production of estradiol and progesterone. Peak HCG levels at
neighboring follicles week 9.
• LH and FSH receptors: upregulated o Start-Peak-Decline of B-HCG in pregnancy: 6-8 days ovulation
• Estrogen: increases – 7-9 weeks – 20 weeks
o Causes proliferation of uterus • Second and Third Trimester: Placenta produces progesterone
o Causes selective negative feedback: ↑ FSH, ↓ LH and fetal adrenal gland-fetal liver-placenta produces estrogen.
Major estrogen: estriol. Human Chorionic Somatomammotropin
OVULATION (DAY 14) or HCS (formerly called HPL) produced through pregnancy
• Occurs 14 days before menses regardless of cycle length o GnRH levels during pregnancy: Decreased
• At the peak of estrogen secretion one day before ovulation, Example of double-negative questions:
estrogen will cause positive feedback on FSH and LH secretion, Q: If fertilization did not occur, which will not happen - no sloughing of of
causing their levels to surge endometrial lining, No division of cells, Release of genetic material, no
thickening of uterine wall?
• Estrogen-induced LH surge triggers ovulation A: Release of genetic material
o Indication that ovulation has taken place: increased
Recommend that you rephrase these questions in the questionnaire. Be careful.
progesterone levels Dr. Banzuela
• Cervical mucus increases, becomes less viscous and more
✔GUIDE QUESTION
penetrable by sperm
The source of estrogen during the second and third trimesters of
• Granulosa cells undergo luteinization to luteal cells pregnancy is the
• Egg cell: has 24 hours to be fertilized (A) corpus luteum
o If fertilized: corpus luteum becomes corpus luteum of (B) maternal ovaries
pregnancy (C) maternal ovaries and fetal adrenal gland
o If unfertilized: corpus luteum will regress to corpus albicans (D) maternal adrenal gland and fetal liver
(E) fetal adrenal gland, fetal liver, and placenta
What do you measure in the urine as sign that ovulation has happened? • Principal steroid secreted by the fetal adrenal cortex: DHEA
Answer: LH. From Physiology BRS, 6th Ed
Dr. Banzuela
LUTEAL PHASE (DAY 14-28)
• Corpus luteum synthesizes both estrogen and progesterone
• Progesterone causes non-selective negative feedback of both LH
and FSH
• ↑ Vascularity and secretory activity of endometrium (preparation
for possible implantation)
• ↑ basal body temperature due to progesterone

MENSES (DAY 0 TO 4)
• Sloughing of endometrium due to abrupt cessation of estradiol
and progesterone
• Spiral arterioles will break
• Menstrual Cycle
Estrogen Progesterone FSH LH
Menstruation ↓ ↓* ↓ ↓
Follicular phase ↑* ↓ ↑ ↓ © Topnotch Medical Board Prep

Ovulation ↑ ↓ ↑ ↑* Egg Cell


Luteal phase ↓ ↑* ↓ ↓ • arrested at prophase I from birth to puberty
Look at the table above. Key points: drop in progesterone levels trigger • Will proceed from prophase I to metaphase II during ovulation
menstruation. Estrogen is the predominant hormone during the • Completion of meiosis during fertilization
proliferative/follicular phase; it causes selective negative feedback. Type of Human Placenta: hemochorial type
Progesterone is the predominant hormone during the secretory/luteal (epitheliochorial is for horses, pigs, ruminants; endotheliochorial type for
phase; it causes non-selective negative feedback. LH surge is the trigger carnivores, hemochorial type for primates, rodents, rabbits)
for Ovulation. LH levels are highest during ovulation. NOT an excretory product of the mother: Glucose (since it’s a nutrient)
Dr. Banzuela
LH triggers both ovulation and luteinization of the granulosa cells into LH
RELAXIN
receptive cells (enabling the granulosa cells to respond to LH levels and
produce progesterone). FSH as the name implies trigger follicular • Protein hormone (NOT A STEROID)
development. Granulosa cells secrete estrogen after being stimulated by • produced by corpus luteum, uterus, placenta and mammary gland
FSH. • Also produced by the prostate gland in males
Follicular phase is the determinant of menstrual cycle length since the • Effects:
luteal phase is relatively constant in duration. o During pregnancy: relaxes pubic symphysis, softens and
Some terms: dilates the cervix
Menorrhagia: Menstrual bleeding more than 7 days. o In males: found in semen, maintains sperm motility and aid in
Polymenorrhea is a term used to describe a menstrual cycle that is shorter sperm penetration
than 21 days.
Menometrorrhagia is excessive and prolonged uterine bleeding PARTURITION
occurring at irregular and/or frequent intervals. • Umbilical Artery: PO2: 60% (very low compared to maternal
Metrorrhagia is abnormal bleeding between regular menstrual periods. artery’s 98% and umbilical vein’s 80%)
Q: Case of a girl who had her first menses, which will regenerate - • At week 24 to birth: terminal sacs in the lungs develop, thus
functional, basal? survival of premature babies is possible
A: functional layer • Progesterone increases threshold for uterine contraction
Dr. Banzuela
FERTILIZATION throughout pregnancy
• Near term: estrogen/progesterone ratio increases → uterus more
• Usually occurs in the Ampulla of the Uterine Tubes
sensitive to contractile stimuli
• Anterior head of the sperm binds to this area in the ovum: Oocyte
• Trigger start of active phase in pregnancy: Oxytocin (mostly)
Zona Pellucida
• Initiating event in parturition: unknown
• portion where chorion attaches is called: Decidua
o Trigger for onset of labor is fetal ACTH
• If fertilization occurs, corpus luteum will be maintained by HCG
o Final event required for conversion of the transitional
produced by the placenta circulation in the newborn to the adult circulatory pattern:
• Implants into the uterine wall: blastocyst functional closure of the ductus arteriosus
• Implantation: occurs 6-7 days after fertilization o Baby’s first breath causes: ↑ PaO2 → ↓ pulmonary vascular
resistance, increased systemic vascular resistance
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• Oxytocin: powerful stimulant of uterine contraction • Serum
• Cross-over question: Mom that cradles baby too much will be o Plasma minus clotting proteins (fibrinogen and clotting
prone to: De Quervain Syndrome (Mommy Thumb) from factors II, V, and VIII) and with higher serotonin content
improper lifting of infants
COMPOSITION OF PLASMA
LACTATION
PLASMA PROTEIN
• Prolactin increases during pregnancy Blood
o Actions block by estrogen and progesterone coagulation Essential component of clotting system
• After parturition, drop in estrogen and progesterone causes proteins
actions of prolactin to manifest Major contributors to oncotic pressure of
• Prolactin may inhibit ovulation for the next 6 months due to Albumin
plasma
inhibition of GnRH (preventing LH surge from ultimately happening)
• Alpha globulins: proteases, antiproteases,
• causes amenorrhea in anorexia nervosa: decreased GnRH (due to transport proteins
decreased leptin associated with decreased mass of adipose tissue)
Globulin • Beta globulins: transferrin & other
• breast milk vs cows milk casein: Less in breast milk transport proteins
✔GUIDE QUESTION • Gamma globulins: immunoglobulins
Which of the following explains the suppression of lactation during OTHERS
pregnancy?
(A) Blood prolactin levels are too low for milk production to occur
Electrolytes • Major ECF cation: Na+
(B) Human placental lactogen levels are too low for milk production to occur Organic • Lipids (fatty acids, cholesterol),
(C) The fetal adrenal gland does not produce sufficient estriol nutrients carbohydrates (glucose) & amino acids
(D) Blood levels of estrogen and progesterone are high Organic • Carried to sites of breakdown or excretion
(E) The maternal anterior pituitary is suppressed wastes (urea, uric acid, bilirubin & ammonium ions)
From Physiology BRS, 6th Ed

8. HEMATOLOGY AND SPECIAL


ENVIRONMENTS PHYSIOLOGY
1. Overview of Blood Cells
2. Red Blood Cells
3. White Blood Cells, Immunity and Infection
4. Antigenicity of Blood and Tissues
5. Hemostasis
6. Inflammation and Wound Healing
7. Physiology in Special Environments

8.1 OVERVIEW OF BLOOD CELLS


COMPOSITION OF WHOLE BLOOD
• Plasma
o Fluid medium of the blood/non-cellular part of the blood
o It is where the cells are suspended
© Topnotch Medical Board Pre
o Composition: 90% water, 9% plasma protein, 1% inorganic
salts, 0.5% lipids, 0.1% sugar
MNEMONICS BLOOD CELL FORMATION
YOUNG LIVER SYNTHESIZES BLOOD.
Yolk Sac à Liver, Spleen à Bone Marrow

© Topnotch Medical Board Prep © Topnotch Medical Board Prep

BLOOD CELL FORMATION o Males: 14-18 g/dl


• 1st Trimester: Yolk Sac / Aortic Gonad Mesonephros o Females: 12-18 g/dl
• 2nd and 3rd Trimester: Liver (with minor contribution from • Percentage of Cells in whole blood: Hematocrit
spleen, LN) o Males: 46 (40-54)
• After birth to puberty: Bone Marrow of all Bones o Females: 42 (37-47)
• Age 20 and above: Bone Marrow of “Centrally-located” Bones o Sign of hemorrhagic shock: Low Hematocrit
• Extramedullary hematopoiesis in full-term infant: always RBCs are LARGER than the capillaries that they pass through. So, RBCs
abnormal would have to bend/flex (like man kneeling) for them to be able to pass
through these narrow capillaries. “Bag pliability” brought by spectrin
enables RBCs to do that. They will have this bag pliability for 120 days, after
8.2 RED BLOOD CELLS which, they will die in very narrow capillaries because they cannot
• Biconcave (due to spectrin) which allows pliability to squeeze bend/flex properly anymore. Where do old RBCs die? What is the
through capillaries “graveyard” of RBCs? Answer: the spleen. What if the spleen is removed,
• Size: 2x8 micrometer where do RBCs come to die then? Answer: the liver.
Defective Cells in G6PD Deficiency: Heinz bodies.
• Protein inside RBC that binds with O2: Hemoglobin Dr. Banzuela

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MNEMONICS RBC Stages • Primary mechanism for change in RBC shape during a sickle cell
“PB PORE” crisis: Polymerization of HbS as it deoxygenated
CELL DESCRIPTION • Found in sickle cell RBC: Hemoglobin S or Hemoglobin SS
Proerythroblast • Synthesis of hemoglobin
starts FORMATION OF HEMOGLOBIN
(or Pronormoblast or Rubriblast) (Source: William’s Hematology 9th Ed)

• Nucleoli disappear
Basophilic erythroblast (Take note: According to
(Macroblast or Early normoblast Junqueira's Basic Histology (15th
or rubricyte) ed), hemoglobin synthesis starts
in basophilic erythroblast stage)
Polychromatic erythroblast • Hemoglobin appears
(intermediate normoblast)
Orthochromatic
erythroblast • Nucleus disappears
(Normoblast or Late normoblast or
metarubricyte)
Reticulocytes • Formed reticulum
(Polychromatic erythrocyte) • Stage that enters blood
• Final Product
• Reticulum disappears
Erythrocyte • Achieves biconcave
shape
Reticulocytes are nicknamed “baby RBCs.” Remember their synonym: © Topnotch Medical Board Prep
polychromatic erythrocyte. This is the form released into the blood. It will
take around 2 days for these reticulocytes to change into mature RBCs.
Dr. Banzuela

IRON METABOLISM
© Topnotch Medical Board Prep
Listen to this audio recording while looking at the figure for iron
metabolism:

IRON METABOLISM
https://qrs.ly/l4ebjnz

Dr. Banzuela

8.3 WHITE BLOOD CELLS, IMMUNITY AND


INFECTION
Immunity
• “Ability of the human body to resist almost all types of
organisms/toxins that tend to damage the tissues and organs”
© Topnotch Medical Board Prep (body’s ability to fight against infection)
HEMOGLOBIN • Divided into Innate Immunity and Adaptive Immunity
HEMOGLOBIN COMPONENTS
IN THE EMBRYO BRANCHES OF IMMUNE SYSTEM
Gower I hemoglobin • ζ2 - ε2 ADAPTIVE
INNATE IMMUNITY
Gower II hemoglobin • α2 - ε2 IMMUNITY
Hemoglobin Portland I • ζ2 - γ2 Specificity Non-specific Extremely specific
Hemoglobin Portland II • ζ2 - β2 Present at birth, does Develops and changes
System
IN THE FETUS not change over time throughout life
• α2 - γ 2 Special antigens of
Hemoglobin F (HbF) Structures shared by
• binds less with 2,3-BPG Triggered by microbial and non-
a group of microbes
AFTER BIRTH microbial agents
• α2 - β 2 Long term memory
Memory No memory
(memory cells)
Hemoglobin A (HbA) • binds more with 2,3-BPG
Same intensity of
• 95% of hemoglobin after birth Improves after each
Adaptation action from
• α2 -δ2 repeated exposure
subsequent exposure
Hemoglobin A2 (HbA2) • 1.5-3.5% of hemoglobin after
Slow: requires several
birth Fast: acts within
Response days before becoming
• α2 - γ 2 minutes
effective
• can be elevated in persons with
Potency Less More
Hemoglobin F (HbF)
sickle cell disease & beta-
Line of 1st line as Develops after
thalassemia defense intrinsically present exposure
Contributed by Frinz Moey C. Rubio, MD
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ADAPTIVE HUMORAL CELL MEDIATED
INNATE IMMUNITY
IMMUNITY IMMUNITY IMMUNITY
• Not sufficient Differentiation of B
Secrete locally acting
Those with severe End result cells into antibody
combined immuno- proteins called
Sufficiency Yes of activation secreting cells called
deficiency disease suffer cytokines
plasma cells
from life threatening
Hyper-
infections I, II, III are antibody
sensitivity IV is cell mediated
• Phagocytes • Lymphocytes (T, B mediated
reactions
• Monocytes and plasma cells)
Components Delayed type
• Macrophages • Antigen presenting Onset Rapid
Cells hypersensitivity
• Neutrophils cells (macrophages,
Antibodies Formed Not formed
• Natural killer cells B & dendritic cells)
Skin test for
Blood From plasma level of development of
Complement Antibodies Evaluation
proteins antibodies delayed type of
Anatomic • Lymph nodes hypersensitivity
• Skin
and • Spleen • Ab synthesis
• Mucous • Macrophage
physiological • Mucosal Associated requires 3 cells:
membranes Cells • Helper T cells
barriers Lymphoid Tissue o T lymphocytes
involved • Natural killer T cells
Favorite topic in the med boards to. Remember: o B lymphocytes
• Cytotoxic T cells
Innate immunity is first-line, non-specific, does not require prior exposure o Macrophage
and less powerful. Adaptive immunity is second-line, specific, requires
prior exposure and is more powerful. Innate immunity – basta walang CELLS OF INNATE IMMUNITY (WBCs, Platelet)
lymphocytes na involved. Adaptive immunity – basta lymphocytes ang WBC APPEARANCE DESCRIPTION
involved. • Most common type,
Analogy: innate immunity – done by security guards (first line, non-specific • Involved in bacterial
(pwede sa magnanakaw, troublemaker, etc.), does not require prior • Multilobed infection (neutrophils
exposure, less powerful (compared sa SWAT team). Adaptive immunity – Neutrophils
nucleus utilize oxidants/ROS to kill
done by SWAT team (second-line (tinatawag pag di kaya ng guards), bacteria) and acute
specific (e.g., hostage-takers), requires prior exposure (may training), more inflammation
powerful) =)
Dr. Banzuela • Weak phagocytes involved
• Bilobed in parasitic infections and
nucleus, stain allergies
Eosinophils
bright red • Highly phagocytic for
with eosin dye antigen-antibody
(immune) complexes
• Least common type, similar
to mast cells, produce
• Bilobed /
histamine, heparin,
trilobed
bradykinin, serotonin
nucleus,
Basophils • Mast Cells: degranulation
largely densely
produces clinical
basophilic
manifestations of Allergy to
(blue) granules
Anaphylaxis. Mast cell
secrete histamine
• Phagocytes, largest of WBC,
• Large,
mature to macrophages in
KIDNEY-
tissues
SHAPED
o Macrophages: activated by
nucleus
interferon gamma,
© Topnotch Medical Board Prep Monocytes • “FROSTED
Links innate to adaptive immunity: Dendritic Cells. These are "Sentinels phagocytizes cellular debris
GLASS” or
that capture, process and present antigens to lymphoid tissues to select and senescent RBCs, acts as
GROUND-
rare, antigen-reactive T-Cell Clones". Also act as sensors responding to APC via MHC II, long life span
GLASS
spectrum of environmental cues by extensive differentiation or maturation. compared to monocytes
cytoplasm
https://pubmed.ncbi.nlm.nih.gov/17278389/ (months to years)
Dr. Banzuela • Small,
TYPES OF ADAPTIVE IMMUNITY biconvex,
• Not a WBC;
HUMORAL CELL MEDIATED non-nucleated
Platelets • involved in hemostasis;
IMMUNITY IMMUNITY cells from
• lifespan 7-10 days
Main cells B-lymphocytes T-lymphocytes megakaryocyt
Originated in bone es
Originated and marrow and Remember the table above. When you hear neutrophils, think bacteria and
Maturation matured in bone completed acute inflammation. When you hear eosinophils, think parasites and
marrow development in allergies. When you hear basophils, think histamine and allergies. When
thymus you hear monocytes, think of immature cells found in the blood. Monocytes
have FROSTED-GLASS cytoplasm and KIDNEY-SHAPED nucleus.
• Extracellular • Intracellular
Macrophages are the mature forms found in the tissues. And finally, when
microbes and their microbes you hear platelets, think “7-10 days.”
toxins o Viruses Sequence of WBC count: (N>L>M>E>B)
• Toxin induced o Parasites NORMAL
Protect
diseases (Leishmania) CELL TYPE VALUE ELEVATED LEVELS MAY INDICATE
against
• Infections o Bacteria (percent)
(virulence related (Mycobacterium, Neutrophil 54-62 Bacterial infection, stress
to polysaccharide Listeria) Mononucleosis, whooping cough,
Lymphocyte 25-33
capsule) • Kills tumor cells viral infections
Malaria, tuberculosis, fungal
Location in Monocyte 3-9
infections
lymph Superficial cortex Paracortical areas Allergic reactions, autoimmune
nodes Eosinophil 1-3
diseases, parasitic worms
Periarteriolar Cancers, chicken pox,
Location in Basophil <1
White pulp lymphoid sheaths hypothyroidism
spleen
(PALS) Dr. Banzuela

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MECHANISM OF INNATE IMMUNITY • Pus formation = battlefield of dead cells and pathogens
• WBCs move through capillary walls into tissue spaces via:
Diapedesis

INNATE IMMUNITY
• Cells of innate immunity (Neutrophils, Macrophages, NK cells)
respond to lipid and carbohydrate sequences in bacterial cells
walls and other substances characteristic of tumor and
transplant cells

ADAPTIVE IMMUNITY
• is caused by a special immune system that forms Antibodies
and/or activated lymphocytes that attack and destroy the specific
invading organism or toxin
• Lymphocytes:
o Main cells of Adaptive Immunity
o Part of body’s defense against cancer

ANTIBODIES / IMMUNOGLOBULINS
• 1015 possible different immunoglobulins; 1015 possible different
T cell receptors
• Variable Portion: determines specificity to antigen
© Topnotch Medical Board Prep
• Constant Portion: determines other properties of antibodies
• Splinter in your finger → Break in the skin → pathogen will enter
the break → Tissue injury occurs • Effect:
o Direct: agglutination, precipitation, neutralization, lysis
• Mast Cells: will release histamine causing vasodilation and
o Indirect: activation of complement system
increased vascular permeability
• Tissue Macrophages
o 1st line of defense
o Present within minutes
o identifies the pathogen → phagocytosis
• Neutrophils Invasion
o 2nd line of defense
o Will start migrating in response to inflammatory cytokines
o Cause Phagocytosis
• Monocytes → Macrophage Invasion
o 3rd line of defense
o Blood monocytes (inactive) are converted to tissues:
macrophage (active)
o This response takes time (at least 8 hours)
• ↑ Monocytes & Granulocyte production by Bone marrow
o 4th line of defense © Topnotch Medical Board Prep
o Takes 3-4 days
o Mediated by TNF, IL-1, GM-CSF, M-CSF
TYPE FUNCTION HEAVY CHAIN STRUCTURE NOTES
• Most abundant type in serum (IgG > IgA > IgM >
• Activates complement
IgD > IgE)
(fixes complement)
• Smallest, responsible for secondary immune
IgG • Opsonizes bacteria γ1, γ2, γ3, γ4 Monomer
response
• Neutralized bacterial toxins
• Only isotype capable of crossing the placenta (IgG
and viruses
Greets the Growing fetus)
• Most produced antibody overall (in mucous
• Localized protection in
membranes) but has lower serum
human body secretions concentrations
(milk, saliva, tears, respiratory,
intestinal, genital tract) • Antibody in intestinal secretion, tears, sweat,
Monomer
• Prevents attachment of (in circulation)
Peyer patches
bacteria and viruses to • Largest mass of lymphoid tissue in the human
IgA α1, α2 body: Gut-associated lymphoid tissue
mucous membranes Dimer
• Does NOTefficiently (with J chain when (GALT)(e.g., Peyer patches)
activate/fix complement secreted) • Protects mucosa via “immune exclusion” (binds to
proteins (which prevents pathogen and prevents it from making contact with
initiating inflammation that can epithelial cells or mucus membranes)
be damaging) • At least in the gut, unusually cross-reactive (coping
with antigenic drift)
• Largest; responsible in primary immune response
Monomer (on B cells)
• Activates complement • Found on the surface of naïve B cells
IgM μ Pentamer (with J
(fixes complement) chain when secreted)
• In terms of complement activation: IgM > IgG due
to greater number of binding sites
• Binds mast cells, basophils
→ cross-links when exposed
• Associated with allergies
to allergen → mediates type
• Most common cause of angioedema: Allergic
IgE I hypersensitivity (via ε Monomer
histamine release)
angioedema (most common: seafood; others:
• Activates eosinophils → milk, egg, nuts)
immunity to parasites
IgD • Has unclear function δ Monomer • Found on the surface of naïve B cells

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Listen to the audio recording of Antibodies while looking at the table above, CYTOKINE
and listen to the audio recording of Complement Proteins while looking at CELL FUNCTION
SECRETED
the image below:
• Cytotoxic lymphocyte of innate
NK Cell ---
immune system
• Cytotoxic lymphocyte that has
NKT Cell --- features of T-lymphocyte and NK
cell
Plasma • Activated Naïve B-Cells;
ANTIBODIES COMPLEMENT PROTEINS ---
Cell • Secretes antibodies
https://qrs.ly/slebjod https://qrs.ly/uqebjog
Dr. Banzuela Delayed reaction allergy is due to activated T cells. Memory T cells come
COMPLEMENT SYSTEM from antigen-naïve T cells, and has uncertain lineage.
• Complement Proteins: targets Ag-Ab complexes Dr. Banzuela

• Plasma proteins from the liver involved in innate immunity


and inflammation
• “Complement” the effects of antibodies
o Opsonization: serve as marker that makes it easier to
phagocytize foreign bodies
o Stimulate Inflammation
o Membrane Attack Complex: perforate foreign organisms →
bacterial cell lysis

© Topnotch Medical Board Prep


CYTOKINES
• Hormone-like molecules that act on nearby cells (paracrine) to
regulate immune responses
• Secreted by lymphocytes, macrophages, endothelial cells,
neurons, glial cells, other types of cells
• Chemokines: superfamily of >40 cytokines that attract neutrophils
and other WBCs to areas of inflammation or immune response
o Also has role in cell growth and angiogenesis
HEMATOPOIETIC GROWTH FACTORS
© Topnotch Medical Board Prep

• Pathways: • Stem Cell Factors (SCF): for proliferation of Hematopoietic Stem Cells
o Classic pathway: triggered by immune complex • CSF (G-, GM- and M-Colony Stimulating Factors - CSF): causes
o Mannose-binding lectin pathway: triggered by lectin binding colonies to proliferate in soft agar
with mannose groups in bacteria • IL-1, IL-6, IL-3: convert pluripotent uncommitted stem cells to
o Alternative / properdin pathway: triggered by contact with committed progenitor cells
various viruses, bacteria, fungi and tumor cells • IL-3: also called multi-CSF (promotes proliferation of all types of
• Causes Opsonization: C3b blood cell)
• Induces inflammation (anaphylatoxin): C3a, C4a, C5a • Chromosome 5: encode for most hematopoietic GF
• Causes WBC chemotaxis: C5a HEMATOPOIETIC GROWTH FACTORS
• Members of the Membrane Attack Complex (MAC): C5b-C9 CELL TYPES
CYTOKINE SOURCE
MNEMONICS COMPLEMENT SYSTEM STIMULATED
Erythrocyte
C3b-O (the robot in Star Wars)
Granulocyte
• C3b – Opsonization IL-1 Multiple cell types
Megakaryocyte
C5a – chemoTAXIs
Monocyte
• Think of a Taxi travelling along the C5 Highway
Erythrocyte
CELLS OF ADAPTIVE IMMUNITY (LYMPHOCYTES) Granulocyte
IL-3 T lymphocytes
CYTOKINE Megakaryocyte
CELL FUNCTION Monocyte
SECRETED
IL-2 • Stimulates cellular immunity IL-4 Basophil T lymphocytes
TH1 IL-5 Eosinophil T lymphocytes
γ-interferon (activated T-Cells)
IL-4 • Interact with B cells in relation to Erythrocyte
TH2 Endothelial cells,
IL-5 humoral immunity Granulocyte
IL-6 fibroblasts,
• Induced in response to bacterial Megakaryocyte
macrophages
Monocyte
infections,
• Help recruit neutrophils & Erythrocyte
IL-6 Fibroblasts,
TH17 IL-11 Granulocyte
monocytes; osteoblasts
IL-17 Megakaryocyte
• Generate harmful inflammatory
Kidney
responses in autoimmune Erythropoietin Erythrocyte
diseases Kupffer cells of liver
Erythrocyte
Treg IL-10 • Dampen T-Cell-driven responses Granulocyte
αβ T • Recognize and bind to MHC SCF Multiple cell types
--- Megakaryocyte
cells proteins and antigen fragments Monocyte
• Seen in GIT mucosa; Endothelial,
γδ T
--- • Form link between innate and G-CSF Granulocyte fibroblast,
cells
acquired immune system monocytes

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CELL TYPES CELL TYPES
CYTOKINE SOURCE CYTOKINE SOURCE
STIMULATED STIMULATED
Endothelial cells, Endothelial cells,
Erythrocyte
fibroblasts, M-CSF Monocyte fibroblasts,
GM-CSF Granulocyte
monocytes, T monocytes
Megakaryocyte
lymphocytes Thrombopoietin Megakaryocyte Liver, kidney
Barrett et al. Ganong’s Review of Medical Physiology. 26th ed. 2019

EXAMPLES OF CYTOKINES AND THEIR CLINICAL RELEVANCE


CYTOKINE CELLULAR SOURCES MAJOR ACTIVITIES CLINICAL RELEVANCE
Activation of T cells and
Implicated in the pathogenesis of septic shock,
IL-1 Macrophages macrophages; promotion of
rheumatoid arthritis, and atherosclerosis
inflammation
Used to induce lymphokine-activated killer cells;
Type 1 (Th1) helper T Activation of lymphocytes, natural
IL-2 used in the treatment of metastatic renal cell
cells killer cells, and macrophages
carcinoma, melanoma, and various other tumors
Type 2 (Th2) helper T As a result of its ability to stimulate IgE
cells, mast cells, Activation of lymphocytes, monocytes production, plays a part in mast-cell
IL-4
basophils, and and IgE class switching sensitization and thus in allergy and in defense
eosinophils against nematode infections
Type 2 (Th2) helper T Monoclonal antibody against interleukin-5 used
IL-5 cells, mast cells, and Differentiation of eosinophils to inhibit the antigen-induces late-phase
eosinophils eosinophilia in animal models of allergy
Type 2 (Th2) helper T Activation of lymphocytes; Overproduces in Castleman disease acts as an
IL-6 cells and differentiation of B cells, stimulation of autocrine growth factor in myeloma and in
macrophages the production of acute-phase proteins mesangial proliferative glomerulonephritis
Levels are increased in diseases. Accompanied
T cells and Chemotaxis of neutrophils, basophils,
IL-8 by neutrophilia, making it a potentially useful
macrophages and T cells
marker of disease activity
Bone marrow stromal Stimulation of the production of acute- Used to reduce chemotherapy-induced
IL-11
cells phase proteins thrombocytopenia
Stimulation of the production of
Macrophages and B interferon γ by type 1 (Th1) helper T
IL-12 May be useful as an adjuvant for vaccines
cells cells and by natural killer cells;
induction of type 1 (Th1) helper T cells
Implicated in many immune/autoimmune
Promotion of inflammatory cell
IL-17 T cells diseases such as rheumatoid arthritis, asthma,
chemotaxis and inflammation
and psoriasis
Macrophages, natural Treatment with antibodies against tumor
Tumor necrosis
killer cells, T cells, B Promotion of inflammation necrosis factor-⍺ beneficial in rheumatoid
factor-⍺
cells, and mast cells arthritis and Chron disease
Lymphotoxin Implicated in the pathogenesis of multiple
Type 1 (Th1) helper T
(tumor necrosis Promotion of inflammation sclerosis and insulin-dependent diabetes
cells and B cells
factor-β) mellitus
Transforming T cells, macrophages, May be useful therapeutic agent in multiple
Immunosuppression
growth factor-β B cells, and mast cells sclerosis and myasthenia gravis
Used to reduce neutropenia after chemotherapy
T cells, macrophages,
Promotion of the growth of for tumors and in ganciclovir-treated patients
GM CSF natural killer cells,
granulocytes and monocytes with AIDS; used to stimulate cell production
and B cells
after hematopoietic stem cell transplantation
Used to treat AIDS-related Kaposi sarcoma,
Induction of resistance of cells to viral
Interferon-⍺ Virally infected cells melanoma, chronic Hepatitis B infection, and
infections
chronic Hepatitis C infection
Induction of resistance of cells to viral Used to reduce the frequency and severity of
Interferon-β Virally infected cells
infections relapses in multiple sclerosis
Used enhance the killing of phagocytosed
Type 1 (Th1) helper T bacteria in chronic granulomatous disease
Activation of macrophages; inhibition Patients with chronic granulomatous disease are prone
Interferon-γ cells and natural
of type 2 (Th2) helper T cells to infections with Staph aureus, Pseudomonas
killer cells species, Nocardia species, fungi (Aspergillus and
Candida albicans)
Barrett et al. Ganong’s Review of Medical Physiology. 26th ed. 2019
Should you memorize the table on cytokines above? Unfortunately, yes. They’ve been asked before. We recommend that you don’t memorize them now.
Makakalimutan niyo kaagad yan. Memorize them on the day of your physiology exam, just a few minutes before it starts. The adrenaline running through your
veins during that time, will help you memorize the table (or at least facilitate familiarity that will give you a fighting chance).
Dr. Banzuela

✔GUIDE QUESTION DEVELOPMENT OF B-CELL AND T-CELL


The ability of the blood to phagocytose pathogens and mount a
respiratory burst is increased by
A. interleukin-2 (IL-2)
B. granulocyte colony-stimulating factor (G-CSF)
C. erythropoietin
D. interleukin-4 (IL-4)
E. interleukin-5 (IL-5) From Ganong Physiology 25 Ed th

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ANTIGEN RECOGNITION AND PRESENTATION 8.4 ANTIGENICITY OF BLOOD AND TISSUES
• MHC-I proteins:” ID” of all host nucleated cells ANTIGENICITY OF BLOOD
• MHC-II proteins: “ID” of all host professional APCs
• Antigen groups most likely to cause blood transfusion reactions
• CD8: in cytotoxic T cells that bind with MHC-I proteins o O-A-B Blood Groups
o MHC-1: coupled to mutant or viral proteins (digested in § Type A: N-Acetyl-Galactosamine
proteosomes) § Type B: Galactose
• CD4: in T-helper cells that bind with MHC-II proteins § Type AB: Both
o MHC-2: concerned with extracellular antigens like bacteria § Type O: None
that are endocytosed (digested in late endosomes) o Rh System
Mnemonic: remember the number “8”. CD4 is matched to MHC-2. CD8 is § Rh (+): has D Antigen
matched to MHC-1. 4x2=8, 8:1=8. § Rh (-): no D Antigen
HIV attacks CD4 (T-Helper cells). When a Rh(-) mom has a Rh(+) baby, fetal RBCs will stimulate maternal
Dr. Banzuela
antibody production during feto-maternal hemorrhage (anti-D IgM
initially, then Anti-D IgG). Reexposure to D antigen in subsequent
pregnancies will produce anti-D IgG in sufficient concentration. This Anti-
D IgG can cross the placenta and cause erythroblastosis fetalis or
Hemolytic Disease of the fetus and newborn (HDFN).
Dr. Banzuela

© Topnotch Medical Board Prep

© Topnotch Medical Board Prep

© Topnotch Medical Board Prep

RED BLOOD CELL SERA


TYPES ANTI-A ANTI-B
O (–) (–)
A (+) (–)
B (–) (+)
AB (+) (+)

RED CELL AGGLUTINATION IN INCOMPATIBLE PLASMA

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© Topnotch Medical Board Prep

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ANTIGENICITY OF TISSUES BLOOD COAGULATION
• Types of organ transplantation CLOTTING
SYNONYMS
o Autograft: Self FACTOR
o Isograft/Syngeneic Graft: Twin Factor I • Fibrinogen
o Allograft: same species Factor II • Prothrombin
o Xenograft: other species Factor III • Tissue factor; tissue thromboplastin
Factor IV • Calcium
8.5 HEMOSTASIS Factor V • Proaccelerin; labile factor; Ac-globulin
Watch the video recording on Steps of Hemostasis while referring to the • Serum Prothrombin Conversion
next table: Factor VII Accelerator
• proconvertin; stable factor
HEMOSTASIS • Antihemophilic Factor
https://qrs.ly/2nebju3 Factor VIII • antihemophilic globulin,
• antihemophilic factor A
• Plasma thromboplastin component
Dr. Banzuela
STEPS OF HEMOSTASIS Factor IX • Christmas factor
STEP DESCRIPTION • antihemophilic Factor B
• Due to local myogenic spasm, • Stuart Factor
1. Vascular Factor X
endothelin 1 (ET-1) • Stuart-Prower Factor
Constriction • Plasma Thromboplastin antecedent
• Prevents further blood loss Factor XI
• Platelet Adhesion: mediated by vWF of • antihemophilic Factor C
ruptured blood vessels walls and Gp1b Factor XII • Hageman Factor
2. Primary Factor XIII • Fibrin-stabilizing factor
of platelets
Hemostasis / Prekallikrein • Fletcher Factor
• Platelet Activation: platelets change
Formation of
shape • Fitzgerald factor
Loose Platelet HMW Kininogen
• Platelet Aggregation: mediated by • High-molecular-weight kininogen
Plug
fibrinogen and Gp2b-3a of platelets ANTICLOTTING MECHANISM
(also by PAF)
• Antithrombin III
• Extrinsic Pathway (initiated by Factor
o Binds to serine proteases in the coagulation system
III or Tissue Factor) and Intrinsic
§ Binding facilitated by heparin
Pathway (initiated by Factor XII or
3. Secondary o Inhibits active forms of Factors IX, X, XI and XII
Hagemann Factor) lead to formation of
Hemostasis / • Thrombomodulin
Thrombin that then converts
Blood Coagulation o Expressed in all endothelial cells except in cerebral
fibrinogen to fibrin
microcirculation
• Fibrin: meshwork that strengthens the o Binds to thrombin and turns it into an anticoagulant
loose platelet plug
• Plasmin
• Due to Fibrinolysin or Plasmin: lyses o Lyse fibrin and fibrinogen
4. Resolution
blood clot o Produce Fibrinogen Degradation Products (FDP) that inhibit
thrombin
o Plasminogen receptors: plenty in endothelial cells; discourages
clot formation

© Topnotch Medical Board Prep

MOA of Heparin: binds to antithrombin III à inactivates thrombin and


Factor Xa
Dr. Banzuela

8.6 INFLAMMATION AND WOUND HEALING


INFLAMMATION
• Complex localized response to foreign substances (e.g. bacteria)
© Topnotch Medical Board Prep o Acute inflammation: think neutrophils
Prothrombin Time (PT) measures the integrity of the Extrinsic Pathway o Chronic inflammation: think macrophages
along with factors common to both intrinsic and extrinsic pathway. Partial • Protective response to prevent further spread of injury
Thromboplastin Time (PTT) measures the integrity of the Intrinsic • Arterioles dilate, capillary permeability increase
Pathway and factors common to both intrinsic and extrinsic pathway.
Dr. Banzuela
• nuclear factor-κ B: plays key role in inflammatory response
(e.g., rheumatoid arthritis)

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WOUND HEALING APR FUNCTION
• Wounds: gain 20% of ultimate strength in 3 weeks, maximum POSITIVE APRs (UPREGULATED IN INFLAMMATION)
tensile strength in 12 weeks but never 70% of the strength of Binds and sequesters iron (nutrient
normal skin Ferritin needed for bacterial growth) to inhibit
Remember this: “Wounds never fully heal… you could only stop the microbial iron scavenging
bleeding.” J • Coagulation factor
Dr. Banzuela Fibrinogen • Promotes endothelial repair
PHASES CELLS FUNCTION • Correlates with ESR
Thrombin formation to stop Serum amyloid A Prolonged elevation → amyloidosis
Hemostasis Platelet
the bleeding ↓ iron intestinal absorption (degrades
Release of bactericidal ferroportin) and ↓ iron release (from
Neutrophils Hepcidin
substances macrophages) → anemia of chronic
Release of angiogenic disease
Inflammation
substance to promote Opsonin; fixes complement and
Macrophage facilitates phagocytosis
capillary growth and
granulation process. C-reactive protein Biomarker involved in measuring
Secretes glycoproteins and ongoing inflammation (nonspecific sign
Fibroblast of ongoing inflammation)
collagen
Epidermal Responsible for Binds free plasma hemoglobin →
cells reepithelialization Haptoglobin prevents loss of iron via the kidneys &
Proliferation protects kidney damage by hemoglobin
**Granulation tissue is
formed from macrophages, Main transporter of copper in blood
-- Ceruloplasmin
fibroblasts, and new plasma
capillaries. NEGATIVE APRs (DOWNREGULATED IN INFLAMMATION)
Remodeling of collagen from Reduction conserves amino acids for
Albumin
type III to type I positive reactants
Remodeling Fibroblast Internalized by macrophages to allow
Myofibroblast: wound Transferrin
contraction. iron sequestration
Transports thyroxine and retinol
ACUTE PHASE REACTANTS (APR)
Transthyretin Carries T4 and retinol-binding protein
• Proteins whose concentration increase/decrease by >25% during (RBP) bound to retinol
inflammatory states Retinol-binding Transports vitamin A from liver to other
• Major Inducer: IL-6 protein (RBP) peripheral tissues
• Other Inducers: IL-1 beta, (TNF)-alpha, and interferon gamma Adiponectin Serves as the “fat-burning” molecule
o TNF (cachectin): involved in cachexia in cancer (thus the name Contributed by Frinz Moey C. Rubio, MD
“cachectin”) and septic shock
• Indirect measure of APRs: ESR 8.7 PHYSIOLOGY IN SPECIAL ENVIRONMENTS
o Characterizes Polymyalgia Rheumatic: Increased ESR MEN VS WOMEN
o RBCs normally remain separated via (-) charges MEN WOMEN
o Products of inflammation (fibrinogen) coat the RBCs → ↓ (-) Overall strength More Less
charge → ↑ RBC aggregation (rouleaux formation – “stack of Strength per
coins”) square cm of x-sec 3-4 kg/cm2 3-4 kg/cm2
o Denser RBC aggregates → fall at a faster rate within a pipette area
tube → ↑ESR Long-distance
↑ ESR ↓ ESR World records Marathon
swimming
• Most anemias • Sickle cell anemia (altered Testosterone Estrogen
• Infections shape → inability to form Effect of hormones
→ more muscle → more fat
• Inflammations dense RBC aggregates) Effect of Exercise Increases size (girth) of skeletal muscles
• Cancer (metastases, • Polycythemia (↑ RBCs
Men are stronger overall than women simply because they have larger
multiple myeloma) “dilute” aggregation factors) body sizes brought by testosterone. But on a per unit area basis, women are
• Renal disease (ESRD, • Heart failure just as strong as men – 3-4kg/cm2.
nephrotic syndrome) • Microcytosis Difference of Anabolic characteristics ng Estrogen and Testosterone:
• Pregnancy • Hypofibrinogenemia Estrogen: builds fat. Testosterone: builds muscles
• Major Prototypical APR: CRP (activates monocytes and other Dr. Banzuela

cytokines)
ENERGY SYSTEMS
NOTES ONSET & DURATION EXAMPLE
Phosphagen 100m dash,
Cell ATP, cell phospho-creatine • First 8-10 seconds
energy system jumping, diving
Glycogen-lactic Anaerobic; reconstitute ATP &
• For 1.3 to 1.6 minutes after phosphagen system used up Tennis, soccer
acid system phosphocreatine
• For unlimited time as long as with energy supply
Oxidative Aerobic; reconstitute ATP,
(glycogen, FA, ketones, amino acids) Long-distance
Metabolism phosphocreatine, Glycogen-lactic
• Fats supply 50% energy requirements after 3-4 hours jogging
(Aerobic system) acid cycle
after glycogen-lactic acid system used up
• Factors involved in muscle performance: muscle strength, power premise that there is continuous use of the muscles. If you stop to rest
and endurance at any time, precursors are replenished, and you will go back to the
• Sometimes used by athletes to increase muscle strength: creatine phosphagen energy system. That’s why specific sports will utilize specific
energy systems. 100m dash for example will utilize the phosphagen energy
(converted to phosphorylcreatine that increases ATP) system exclusively – dahil kung competent athlete ka dapat tapos yang
• Greatest determinant of muscle strength: Muscle Size 100m dash in around 10 seconds at hindi 2 minutes. =) Tennis and soccer
• Source of most energy used for long-term muscle contraction: will utilize exclusively the glycogen-lactic acid system naman – because you
oxidative metabolism have frequent breaks in muscle use (e.g., in tennis: palo…pak! Rest…
palo…pak! Rest… Yosi muna… palo…pak! Rest… Tambay muna… =)
The energy system used in the first 10 seconds of athletic competitions is
Marathon will exclusively use the aerobic system because you don’t stop
the phosphagen energy system (the existing ATP and creatine phosphate in
every 2 minutes while running a marathon.
the cell). After 10 seconds, for the next almost 2 minutes, anaerobic system Dr. Banzuela
(glycogen-lactic acid system) is utilized. Only after approximately 2
minutes will you use the aerobic system. All of these are based on the
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ADAPTATION TO HIGH ALTITUDE ADAPTATIONS TO FLIGHT
DESCRIPTION ANSWER POSITIVE G FORCES NEGATIVE G FOCES
Unacclimatized • Pilot pushed against • Pilot pushed against
Description
person, Acute • 12,000 feet his seat his seatbelt
Effects are felt at: Danger • More dangerous • Less dangerous
Unacclimatized • Blood shunted to
• 18,000 feet
person, Seizures at: the Head
Unacclimatized o May result in
• 23,000 feet Blood
person, Death at • Lower Extremities “red-out” of the
Shunted To
Natural eyes and transient
• Larger heart, lungs, shorter height
Acclimatization psychotic
• ↑ RR → respiratory alkalosis → renal disturbances
compensation → normal pH • +6 to +10G →
• Polycythemia via EPO → ↑ 2,3 BPG → blackouts, LOC,
• -20G → death
shift to R of O2-HgB Dissociation Limit death
Mechanisms for
Curve • +20G → Vertebral
Acclimatization
• ↑ Diffusing Capacity for O2 Fracture
• Angiogenesis via VEGF
• ↑ ability of cells to use O2 → ↑ ADAPTATION TO SPACE
mitochondria • Acute Effects
Natanong na dati yang 12,000 feet, 18,000 feet at 23,000 feet na yan (these o Motion sickness
are the numbers written in Guyton). But the options given at that time are o Translocation of fluids
in centimeters and not in feet. =) Life gets crazy sometimes. So, remember o Diminished physical activity
2.54cm=1 inch, 12 inches = 1 foot. • Chronic Effects
Dr. Banzuela
• High Altitude predisposes to Hypocalcemic Tetany (e.g., calf o Decreased blood volume
muscles cramping) because: Plasma proteins are more ionized o Decreased RBC
under alkalotic conditions, which provide more protein anion o Decreased muscle strength
to bind with Calcium causing hypocalcemia o Decreased maximum cardiac output
o Loss of calcium and phosphate from bones → decrease in bone
• Returns to normal after acclimatization: Cardiac Output
mass

DIVING PHYSIOLOGY
• Maximum” safe” depth: 200 feet below sea-level
• Rapid ascent causes: nitrogen bubble formation in the blood
(decompression sickness)
o Bends: pain in the extremities
o Chokes: difficulty breathing

END OF PHYSIOLOGY MAIN HANDOUT

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DISCLOSURE
The handouts/review materials must be treated with utmost confidentiality. It shall be the responsibility of the person, whose name appears therein, that the handouts/review materials are not
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recommended review books and other materials listed below.
THIS HANDOUT IS NOT FOR SALE!

SOURCES: DANCING IN THE MOONLIGHT


1. BRS Physiology 6th Edition by Linda Costanzo, 2015, Published: Lippincott and Williams &
Wilkins Enrico Paolo C. Banzuela, MD
2. BRS Physiology 7th Edition by Linda Costanzo, 2019, Published: Lippincott and Williams & (Facebook Post after The Med Boards)
Wilkins
3. Ganong Review of Medical Physiology, 23rd Edition, by Barrett, Kim , Barrett, Kim E., Barman,
Susan, Boitano, Scott, Brooks, Heddwen, Published: New York : McGraw-Hill Medical, 2010 "Sir, 30 minutes to 1-hour po yung duration - "How to Establish your
4. Ganong Review of Medical Physiology, 25th Edition, by Barrett, Kim , Barrett, Kim E., Barman, Practice Ethically and Effectively" - 1.) How to choose area of practice,
Susan, Boitano, Scott, Brooks, Heddwen, Published: New York : McGraw-Hill Medical, 2016 hospitals, 2. How to set-up your clinic - room size, secretary, materials,
5. Ganong Review of Medical Physiology, 26th Edition, by Barrett, Kim , Barrett, Kim E., Barman,
Susan, Boitano, Scott, Brooks, Heddwen, Published: New York : McGraw-Hill Medical, 2019 accounting, 3. How to "market" your practice ethically 4. How to deal with
6. Costanzo Physiology 6th Edition by Linda Costanzo Published in Philadelphia, Pennsylvania: your competition ethically 5. Tips on how to work effectively with your
Saunders/Elsevier, 2018 superiors, residents, nurses, admin staff 6. Tips in managing common
7. Pre-Test Physiology, 14th Edition by Patricia Mettin, published: McGraw-Hill Medical, 2014
8. Guyton & Hall Textbook of Medical Physiology 12th Edition by Hall, John &, Guyton, Arthur C. , , problems - how to charge, dealing with med reps, referring to other
Published in Philadelphia, Pennsylvania: Saunders/Elsevier, 2011 specialists, dealing with hospital politics, etc.”.
9. Berne & Levy Physiology 6th Edition by Berne, Robert M., 1918-2001., Koeppen, Bruce M.,
Published: Philadelphia : Mosby/Elsevier, 2008 … and so I texted the consultant. But he begged off citing his busy schedule.
10. Kaplan Medical Step 1 Lecture Notes (Physiology) 2010 I asked another one. He also said that he's too busy, despite initial
11. Medical Physiology: Big Picture by (author) Jonathan Kibble, Colby Halsey, Published: Lange
12. Harper’s Illustrated Biochemistry 27th Edition by Murray, Robert K. by Lange
interest. Texted another consultant, and this time, was totally ignored. =)
13. Basic and Clinical Pharmacology 11th Edition by Katzung, Bertram G., Published: New York : And so, a day before the start of our moonlighting seminar, we're frantically
McGraw-Hill Medical, 2009 searching for someone who can deliver this lecture.
14. Harrison’s Principles of Internal Medicine, 18Th Edition
15. SBCM Physiology Lectures
16. Various Internet Websites including https://ods.od.nih.gov/factsheets/Potassium- This moonlighting seminar is very close to my heart because my mom was
HealthProfessional/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7009052/ almost killed by a moonlighting physician/moonlighter.
4 years ago, at around 3am, she had severe, unremitting asthma attack
(status asthmaticus) at home that eventually led to cardiac arrest. Still
wearing our night clothes, and while applying CPR, we rushed her to the
nearest hospital just in front of our village. In the car, I can feel her ribs break
while applying emergency chest compressions, her body limped, her skin

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TOPNOTCH MEDICAL BOARD PREP PHYSIOLOGY MAIN HANDOUT BY DR. ENRICO PAOLO C. BANZUELA
For inquiries visit www.topnotchboardprep.com.ph or https://www.facebook.com/topnotchmedicalboardprep/
This handout is only valid for October 2023 PLE batch. This will be rendered obsolete for the next batch since we update our handouts regularly.
changing from pale to ashen gray. There was only one thing in my mind: 4 What if what happened to my mom happened to me? What if this happened
minutes. In 4 minutes, without oxygen, she'll be brain-dead. Her body may to other people, especially those without any medical background?
still be here, but her mind won't be. I told my dad to drive faster.
I got angry again. We've had lecture on Ethics, and Legal Medicine and Juris…
Finally, we reached the hospital. Upon seeing the ashen-gray body of my but it never really strikes home until you experienced it.
mom, brought in our old family car, with us dressed in "pambahay" clothes,
the moonlighting physician at the ER of this secondary hospital stopped us And then at last, sleep came. We were awakened by the nurse and was told
and said: "Wag nyo na po siyang ibaba at dalhin dito, i-rush nyo na po sya sa that my mom was awake. Since she was intubated, she was given this
FEU" "keyboard" thing for her to type her responses to questions. At that point, I
was already resigned to the fact that her mind might be gone now. I was just
I flared up immediately and told the doctor that my mom arrested and had hoping that she'll at least be able to recognize us. Kahit yung man lang.
status asthmaticus. He insisted that they cannot handle her case. So, I said So, she "typed": "P"… "A"… "P"… "A…" "BAYARAN MO UTANG MO" =)
the magic words: "Doctor po ako. Bigyan nyo ng epi at i-intubate natin yung
mommy ko." It finally dawned on the moonlighting physician that a lawsuit And everybody burst into laughter. Ok, memory intact, calculation probably
is just around the corner, so he finally admitted her. intact, communication intact… I was grinning from ear-to-ear.

The first thing he did? He got an ECG. I think my BP went from HPN Stage 1 She stayed in the ICU for two more weeks, in the hospital for a
to HPN Stage 2 at this point. I know that the reason he got did that was to month. Friends, relatives, former students visited. With each doctor, I
document that I brought my mom arrested. So, I shouted at him to stop, and discussed our experience with the moonlighter.
to give my mom some epi. Well, I think he went from "Scared of Lawsuit
Stage 1" to "Scared of being Killed on the Spot by a Very Big Guy Stage 2" =) I later learned that the nurses on duty in that hospital made an incident
So, he went to the pushcart in the ER… and there was no epi! He immediately report to the hospital director regarding the moonlighter's actions. He was
rushed to the pharmacy. Epi found. A few minutes after it was given, I heard ultimately relieved of his duties.
my mom breathe again, felt her heart beating again. I looked hard at the
moonlighting physician, and saw, in his eyes, inexperience. And so, I told my
After a year, we started giving this moonlighting and pre-residency seminar
dad not to have my mom intubated here. We rushed her to FEU. Literally in
here in Topnotch. General physicians, the backbone of the medical
a few seconds, she was admitted, intubated, and immediately referred to
profession, have oftentimes been "mistrained" by their own experiences
specialists.
after passing the med boards. Natuto sa nakasanayan, natuto rin ng maling
pamamaraan.
It's one thing to learn BLS and ACLS and apply it yourself to other
patients. It's a different thing altogether seeing someone else apply it to
We gave them practical lectures on Internal Medicine, Pediatrics, Ob-Gyne,
your mom. My mom was awake, but incoherent, and flailing her arms wildly.
and Surgery that moonlighters need. We conducted workshops on
I wanted to cry, but I can't. The shock is still there. Fleeting images of nurses
intubation, suturing, and basic casting/splinting. We gave lectures on
and long-term care entered my mind. It's probably been more than 4
Medical Jurisprudence (practical ones like "how to avoid a lawsuit", "how to
minutes. I talked to my dad and sister and told them to prepare for the
transfer patients from one hospital to another", "how to fill up
worst.
medical/death certificates properly") and Ethics. We did life planning –
setting goals for your family, career, etc. We even had talks about savings
I was angry at the moonlighter. Because I've heard it enough from the
plan and how to invest in stocks and other financial instruments. And
horror stories of other physicians and patients why he acted the way he
finally, we presented them with career options – doctors from the Doctors
did. Seeing the patient arrested and in need of intubation, with the patient's
to the Barrios Program, from politics, from residency, from moonlighting…
family looking destitute (hey, no time naman kasi to change from our
they each have their moment to share their story and inspire these general
pambahay clothes), he didn't want the hassle of managing a toxic patient at
physicians. Hindi lang moonlighting, residency, at USMLE ang choices ng
3am in the morning, with the extended hardship of trying to transfer an
mga batang doktor. Maraming, marami pa.
intubated charity patient to another hospital. It might prolong his duty, get
him in trouble legally if the patient dies, get him a scolding from the hospital
director on why he admitted such a toxic charity patient. We kept the price low so that more GPs can be trained. We added
improvements gradually – we're currently conducting our first ever BLS-
ACLS activity immediately after the moonlighting seminar, and in the future,
Of course, he knew that my mom's case was a true emergency, but he's
we hope to add BEST (Basic Emergency Skills in Trauma), a job fair, CME
counting on the fact that I may not. When I told him I was a doctor, he got
accreditation, and perhaps PMA registration onsite.
rattled. Because both of us knew that doctors are required by law to render
emergency care.
The way I see it, if we can have just one more doctor who will value patient
well-being above anything else, one more doctor who's happy with the
And that was the exact moment that I finally cried.
career path he's chosen, one more doctor who can afford to send his son or
daughter to the school of his choice because he's a little more financially-
I cried more than anything else, because of the irony of it all. We train secure thanks to the moonlighting seminar… then we would have done our
medical graduates in the best way possible for them to pass the med boards part.
and practice immediately… only to have them practice unethically and
incompetently such that they may ultimately be the cause of our own
...and my mom's experience, our experience, with the moonlighter, won't be
death. Teach them for months, only for them to practice with personal
for naught. =)
convenience in mind rather than the patient's well-being.
And then the "What Ifs" came. What if I wasn't there, what if it was just my By the way, we did find someone to lecture on "How to Establish your
dad who brought her to moonlighting physician? Practice Ethically and Effectively" =)

To all our participants and teachers, thank you very much! =)

TOPNOTCH MOONLIGHTING AND PRE-RESIDENCY SEMINAR


After you pass your med boards, we would like to invite you to join the Topnotch Moonlight and Pre-Residency Seminar. It will teach you the knowledge,
attitudes and skills needed as a General Physician (especially as a moonlighter and resident), provide you with information on various career choices, and teach
you things important in life but may not have been taught during med school.
By tradition, this seminar will start approximately 10 days after the last day of the Med Boards. Tentatively for P4,500. Here’s the schedule for LAST BATCH
(March-April 2023) to give you an idea what’s in store during this seminar:

TOPNOTCH ONLINE MOONLIGHTING AND PRE-RESIDENCY SEMINAR setting. (CHED Program Outcome 3)
SCHEDULE 5. Apply principles in synergizing their work with other members of the health care
MARCH-APRIL 2023 team (e.g. nurse, med tech). (CHED Program Outcome 5)
6. Discuss guidelines on how to practice in the moonlighting and residency setting
LEARNING OUTCOMES FOR THE TOPNOTCH MOONLIGHTING AND PRE- ethically and in accordance with Philippine laws. (CHED Program Outcomes 8,9)
RESIDENCY SEMINAR OUTCOMES 7. Discuss strategies in applying to local and international residency programs, and
At the end of the two-week training seminar, the licensed Topnotch MD must be able to: other career opportunities offered for general physicians here and abroad. (CHED
1. Create appropriate management plans of common emergent, out-patient, ward and Program Outcome 7, 10)
surgical cases seen by a General Practitioner in the moonlighting setting. (CHED 8. Design a research proposal in collaboration with their participants. (CHED Program
Program Outcomes 1, 2, 3, 6, 7) Outcome 4)
2. Correctly perform procedures expected of a General Practitioner (intubations, 9. Write career, family and personal plans taking into consideration their niche in the
casting/splinting, suturing) with confidence. (CHED Program Outcome 1) systems-based approach to healthcare, their own social accountability, interests
3. Correctly interpret ECG, Chest-Xray, CT-Scan, MRI, and common laboratory and dreams in life. (CHED Program Outcome 6, 10)
findings in the moonlighting setting. (CHED Program Outcome 1) 10. Write their own Resume in the correct format and style. (CHED Program Outcome
4. Discuss basic leadership strategies and principles applicable to the health care 2, 7)

TOPNOTCH MEDICAL BOARD PREP PHYSIOLOGY MAIN DIGITAL HANDOUT BY ENRICO PAOLO C. BANZUELA, MD Appendix
For inquiries visit www.topnotchboardprep.com.phor https://www.facebook.com/topnotchmedicalboardprep/
This handout is only valid for the October 2023 PLE batch. This will be rendered obsolete for the next batch since we update our handouts regularly.
TOPNOTCH MEDICAL BOARD PREP PHYSIOLOGY MAIN HANDOUT BY DR. ENRICO PAOLO C. BANZUELA
For inquiries visit www.topnotchboardprep.com.ph or https://www.facebook.com/topnotchmedicalboardprep/
This handout is only valid for October 2023 PLE batch. This will be rendered obsolete for the next batch since we update our handouts regularly.
DAY 1- MARCH 23, THURS- INTRODUCTION TO MOONLIGHTING SEMINAR; 11:00am-12:00pm- Life of a PNP Medicolegal Officer
ETHICS FOR MOONLIGHTER 12:00pm-1:00pm- LUNCH
1PM-2PM- Opening Remarks and Orientation 1:00pm-2:00pm- Trends in Aesthetic Medicine
2PM-2:30PM- Awarding of the Top 10 2:00-3:00pm- How to handle patients for hemodialysis
2:30-3:30PM- Career Options after the Med Boards
3:30PM-4:30PM- Medical Ethics in Primary Care Medicine DAY 7- MARCH 31, FRIDAY- INTRODUCTION TO THE DOCTORS TO THE BARRIOS;
TIPS FOR TAKING THE AUSTRALIAN, UK PLAB; US MEDICAL LICENSURE EXAMS
DAY 2- MARCH 24, FRIDAY- PREPARING FOR AN INTERVIEW AND RESUME 8:00am- 8:15am - Introduction to the Day’s Activities
BUILDING; SYNERGIZING THE PHYSICIAN-NURSE RELATIONSHIP FROM THE 8:15am-10:30am- Introduction to the Doctors to the Barrios Experience
POINT OF VIEW OF A NURSE; RESEARCH IDEAS 10:30am-12nn- Tips on Taking the Australian Medical Exam
8:00am- 8:15am - Introduction to the Day’s Activities 12:00-1:00pm- LUNCH
8:15-9:30am- How to Write Proper Resume and Preparing for your Interview 1:00-2:00pm- Tips on Taking the UK Professional and Linguistic Assessments Board
9:30-10:30am- Synergizing the Physician-Nurse Relationship 2:00-3:00pm- Tips on Taking the USMLE
10:30-12:00nn- How to create research idea, conduct optimal literature review, and write 1. Basic information about Foreign Exams– how it’s conducted, cost, where
a research proposal and how to apply
2. How to Study for the Exam; Tips on how to be matched
MARCH 25, SATURDAY- NO CLASSES APRIL 1, SATURDAY- NO CLASSES

DAY 3- MARCH 26, SUNDAY- LEGAL ASPECT OF MOONLIGHTING; MANAGEMENT DAY 8- APRIL 2, SUNDAY- SURGERY FOR MOONLIGHTERS AND SUTURING
OF EMERGENCY AND TRAUMA CASES; PATIENT ROUNDS AND PROGRESS WORKSHOP; DONNING AND DOFFING OF PERSONAL PROTECTIVE EQUIPMENT
NOTES 8:00am- 8:15am - Introduction to the Day’s Activities
8:00am- 8:15am - Introduction to the Day’s Activities 8:15am-11:00am – Basic Surgery
8:15am-11:30am- Legal and Ethical side of Moonlighting 1. How to give ATS, TeANA properly and appropriately
1. Legal Basis for Moonlighting 2. Managing V-A Injuries
2. Written and Unwritten Rules of Moonlighting 3. Managing Gunshot and Stab Wound Injuries
3. How to Avoid Lawsuits based on Actual Cases in the Philippines for the 4. Managing Burn Patients
level of moonlighter and hospital resident 5. Tips in mass excision, I and D, ungiectomy
4. How to Write a Proper Medical Certificate and Death Certificate 6. Proper techniques in Circumcision
5. How to Properly Charge Patients for Services Rendered 7. Proper techniques in the suturing of Scalp, Face, Extremities
6. How to Transfer a Patient to Another Hospital Properly 8. Chest Tube Insertion – Video Only; along with tips from Dr.Antonio
7. How to Deal with Various Health Cards (Practical Tips) 9. Lumbar Tap Insertion – Video Only; along with tips from Dr.Antonio
8. How to Legally Deal with your co-workers – Nurses, Fellow Moonlighters, 11:00am-11:30am - Basic Suturing Technique Workshop
Consultants, Hospital Staff Materials:
11:30am-12:30pm-LUNCH *suturing set including scalpel, needle holder, scissors, expired sutures (with needle)
12:30am-4:00pm- Diagnosis and Management of ER Cases 11:30am-12nn- Aseptic Technique, Donning and Doffing of PPEs
1. How to Man an Emergency Room 12nn-12:30pm- Circumcision
2. Application/Sources needed
3. ER Equipment DAY 9- APRIL 3, MONDAY- FINANCIAL WEALTH AND HEALTH FOR THE
4. Approach to Influenza Like Illness Symptoms MOONLIGHTER AND THE RESIDENT; ALL ABOUT BANKING
5. Code Blue 8:00am- 8:15am - Introduction to the Day’s Activities
6. How to give inotropes 8:00-12:00nn- Stocks and Investments for the Busy Resident and Moonlighter
7. Approach to Anaphylaxis 12:00-1:00pm- LUNCH
8. Approach to Hypotension and Shock 1:00pm-4:00pm- All about Banking
9. Approach to Syncope 1. How to open savings and current account
10. Approach to Cardiac Dysrhythmia 2. How to Apply for a credit card
11. Approach to Chest Pain 3. How to properly issue checks
12. Approach to Difficulty of Breathing 4. Different types of loans and how to avail of these loans
13. Approach to Alcohol Intoxication
14. Approach to Seizures DAY 10- APRIL 4, TUESDAY- BASICS OF TELECONFERENCE; HEALTH AND LIFE
15. Common First aid on snakebites, jellyfish, poisoning, etc. INSURANCE; OB-GYN FOR THE MOONLIGHTER
4:00pm-5:00pm Daily Rounds and Progress Notes 8:00am- 8:15am - Introduction to the Day’s Activities
8:15am-9:30am- Basics of Teleconference
DAY 4 - MARCH 27, MONDAY- PRACTICAL IMAGING PEARLS; ROAD TO 9:30am-11:00am- The must-knows of health and life insurance
ALTERNATIVE MEDICINE; SETTING-UP YOUR OWN CLINIC FROM AN MD-MBA 11:00am-12:00pm- LUNCH
STANDPOINT; OCCUPATIONAL HEALTH FOR MOONLIGHTERS 12:00pm-3:00pm- OB-GYN for Moonlighters
8:00-8:15am - Introduction to the Day’s Activities 1. Basic Principles in Prenatal Care
8:15-10:00am- CXR and Fracture Interpretation, Basic CT Scan Interpretation 2. Delivering babies in the Hospital Setting
CXR and Fracture Interpretation, Basic CT Scan Interpretation 3. Delivering babies in the Emergency, Non-Hospital Setting (e.g. at home)
10:00-11:30: Occupational Health for the Moonlighter 4. Management of STDs
11:30-12:30nn- LUNCH 5. Contraception
12:30pm-1:00pm Road to Alternative Medicine 6. Techniques for Pap smear and Internal Examination
1:00pm-2:00pm– Setting Up a Clinic from an MD-MBA standpoint
DAY 11- APRIL 5, WEDNESDAY- I.M. FOR MOONLIGHTERS; ESSENTIAL
DAY 5 - MARCH 28, TUESDAY- PEDIATRICS FOR MOONLIGHTERS; MOONLIGHTING SKILLS; LABORATORY AND ECG INTERPRETATION
8:00am- 8:15am - Introduction to the Day’s Activities 8:00am- 8:15am - Introduction to the Day’s Activities
8:15am- 3:00pm- Diagnosis and Management of Pediatric Cases 8:15am-11:30am- Diagnosis and Management of Adult Cases
1. Fluid Management (Computation of Fluids, when to fast drip, etc.) 1. Pneumonia, URTIs, Asthma, COPD
2. Approach to Fever 2. UTIs
3. Approach to Pediatric Rashes 3. DM
4. Approach to Diarrhea, Vomiting 4. HPN
5. Approach to Abdominal Pain (how to differentiate appendicitis vs colic vs 5. Approach to the Jaundiced Patient
cholecystitis vs PUD, etc) 6. Approach to Poisons and Snakebites
6. Dengue 7. Approach to Electrolyte Abnormalities (Hypo- and Hyper-kalemia, Hypo-
7. Typhoid and Hypercalcemia, etc)
8. Allergies 8. Pain Medications (indications, dosage, contraindications, side effects)
9. Ascariasis and other Helminthic Infections 9. Management of Neuro Emergencies
10. Acute Otitis Media/Externa 11:30-12:30pm- LUNCH
11. Conjunctivitis 12:30pm-1:30pm- Dealing with Abnormal CBC
12. Drug computation of common Pediatric Drugs ( especially 1:30pm-2:30pm- Management of electrolyte abnormalities
diphenhydramine, paracetamol, diazepam, common antibiotics) 2:30pm-3:00pm- ABG Interpretation
12:00pm-1:00pm LUNCH 3:00pm-5:00pm- Basic 12L ECG Interpretation

MARCH 29, WEDNESDAY- NO CLASSES APRIL 6 TO APRIL 9- NO CLASSES

DAY 6- MARCH 30, THURSDAY - ORTHOPEDIC EMERGENCIES, SPLINTING DAY 12- APRIL 10, MONDAY- TECHNIQUES OF ENDOTRACHEAL INTUBATION;
WORKSHOP; INTRODUCTION TO AFP MEDICAL CORPS; LIFE OF A PNP ADULTING 101
MEDICOLEGAL OFFICER; TRENDS IN AESTHETIC MEDICINE; HEMODIALYSIS 8:00am- 8:15am - Introduction to the Day’s Activities
FOR THE MOONLIGHTER 8:15- 10:30am- Endotracheal Intubation Workshop-ONLINE (including indications,
8:00am- 8:15am - Introduction to the Day’s Activities techniques, post-intubation orders)
8:15-10:00am- How to Handle Common Ortho Emergencies and Casting workshop
10:00am-11:00am- Entering the Military Life
TOPNOTCH MEDICAL BOARD PREP PHYSIOLOGY MAIN DIGITAL HANDOUT BY ENRICO PAOLO C. BANZUELA, MD Appendix
For inquiries visit www.topnotchboardprep.com.phor https://www.facebook.com/topnotchmedicalboardprep/
This handout is only valid for the October 2023 PLE batch. This will be rendered obsolete for the next batch since we update our handouts regularly.
TOPNOTCH MEDICAL BOARD PREP PHYSIOLOGY MAIN HANDOUT BY DR. ENRICO PAOLO C. BANZUELA
For inquiries visit www.topnotchboardprep.com.ph or https://www.facebook.com/topnotchmedicalboardprep/
This handout is only valid for October 2023 PLE batch. This will be rendered obsolete for the next batch since we update our handouts regularly.
APRIL 11, TUESDAY- ONSITE ENDOTRACHEAL INTUBATION

DAY 13- APRIL12, WEDNESDAY- MOONLIGHTERS AND RESIDENCY PANEL TALK;


FINDING YOUR NICHE IN THE MEDICAL FIELD
8:15am-9:00am-Panel Discussion- Residents talk about their residency experiences
9:00am-10:00am- Panel Discussion- Different Moonlighting Experiences of 3
Moonlighting Physicians
10:00-11:30pm: Leadership for MDs
11:30-12:30pm- Mini job fair
12:30pm- Awarding of Certificates

Topnotch Moonlighting and Pre-Residency Seminar Onsite 2019

Topnotch Moonlighting and Pre-Residency Seminar Onsite March 2023

TOPNOTCH MEDICAL BOARD PREP PHYSIOLOGY MAIN DIGITAL HANDOUT BY ENRICO PAOLO C. BANZUELA, MD Appendix
For inquiries visit www.topnotchboardprep.com.phor https://www.facebook.com/topnotchmedicalboardprep/
This handout is only valid for the October 2023 PLE batch. This will be rendered obsolete for the next batch since we update our handouts regularly.

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