PBS 2 (2018): HUMAN PHYSIOLOGY AND PATHOPHYSIOLOGY

Institute of Pharmacy S.Y. 2022 - 2023

1st Year I 2st Semester I Finals
Prof. Joshua Kenneth Ng

attention. ● Keeps the heart in a stable location in the mediastinum,

● If any symptoms like chest pain, headache, facilitates its movements, and separates it from the
shortness of breath, or visual changes occur lungs and other mediastinal structures
when blood pressure is this high, medical care The pericardium consist of two layers:
in the emergency room is needed. 1. Fibrous pericardium
● Conical-shaped sac, tough, outermost layer of the
CARDIOVASCULAR (LEC) pericardium
● A layer of connective tissue that helps to hold the heart in
TYPES OF CIRCULATION place
● Defines the borders of middle mediastinum
1. Pulmonary Circulation
2. Serous pericardium
● is the transport system that delivers deoxygenated blood
● Closed sac
from the heart to the lungs, where it is re-saturated with
● A layer of serosa that lines the fibrous pericardium
oxygen before it is released into the systemic circulation
● Reduces friction as the heart beats
2. Systemic Circulation
● It ensures that all bodily tissues have a functioning blood
Serous pericardium is made of two layers:
supply. It transports oxygen and nutrients to the cells
1. Parietal pericardium
while also collecting carbon dioxide and waste materials.
● Outer layer of pericardium
● Lines the fibrous pericardium
FUNCTIONS OF THE HEART
● Parietal pericardium is composed of two layers:
● The heart is a muscular organ that is essential for life ○ Serosal lining (thin red line)
because it pumps blood through the body. Like a pump ○ Fibrous sac (thicker yellow line)
that forces water through a pipe, the heart contracts 2. Visceral pericardium
forcefully to pump blood through the blood vessels of the ● Also known as epicardium
body. Together, the heart, the blood vessels, and the ● Lines the exterior surface of the heart
blood make up the cardiovascular system. ● composed of a single layer of serosal
● Although it is a single structure, the heart is actually two
pumps in one. The right side of the heart pumps blood to Pericardial activity
the lungs and back to the left side of the heart through ● Lies between the between the parietal and visceral
vessels of the pulmonary circulation. The left side of the pericardium
heart pumps blood to all other tissues of the body and Pericardial fluid
back to the right side of the heart through vessels of ● Reduces friction as the heart beats
systemic circulation. Location of the Heart in the Thorax
1. Generating blood pressure
● Contractions of the heart generate blood pressure, which
forces blood through the blood vessels.
2. Routing blood
● The heart separates the pulmonary and systemic
circulations, which ensures the flow of oxygen rich blood
to tissues

SIZE, FORM, AND LOCATION OF THE HEART

● The adult heart is shaped like a blunt cone and is
approximately the size of a closed fist.
● It is larger in physically active adults than in less active
but otherwise healthy adults. The heart generally
decreases in size after approximately age 65, especially
in people who are not physically active
● The heart is located in the thoracic cavity between the
two pleural cavities that surround the lungs.
● The heart, trachea, esophagus, and associated structures
form a midline partition, the mediastinum
(me′dē-as-tī′nŭm). The heart is surrounded by its own
cavity, the pericardial cavity (peri, around + cardio, heart).

ANATOMY OF THE HEART

Pericardium
● Also known as Pericardial sac
● A double layered, closed sac that surrounds the heart.

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Institute of Pharmacy S.Y. 2022 - 2023
1st Year I 2st Semester I Finals
Prof. Joshua Kenneth Ng

● Carries blood to the rest of the body

Right pulmonary artery
● Takes deoxygenated blood from the pulmonary trunk and
transports it to the right lung where the blood vessel then
branches into the lungs and gas exchange takes place,
re-oxygenating the blood
Right pulmonary veins
● Blood vessels that transfer freshly oxygenated blood
from the right lung to the left atria of the heart
Right atrium
● Receives oxygen-poor blood from the body and pumps it
to the right ventricle
Coronary sulcus
● Extends around the heart
● Separates the atria from the ventricles
Right coronary artery
● One of two main coronary vessels that supply the
myocardium
● The heart is located within the thoracic cavity, medially ● Supplies blood to the right ventricle, the right atrium, and
between the lungs in the space known as the the SA (sinoatrial) and AV (atrioventricular) nodes, which
mediastinum regulate the heart rhythm.
● Within the mediastinum, the heart is separated from the Left main coronary artery
other mediastinal structures by a tough membrane ● Supplies blood to the left side of the heart muscle (the
known as the pericardium left ventricle and left atrium)
● The base of the heart, located deep to the sternum, Right ventricle
extends superiorly to the second intercostal space ● Pumps the oxygen-poor blood to the lungs
● The apex of the heart is located deep to the fifth Aortic arch
intercostal space ● Segment of the aorta that helps distribute blood to the
head and upper extremities via the brachiocephalic trunk
and the left subclavian artery
External Anatomy of the Heart ● Plays a role in blood pressure homeostasis
● The right and left atria are located at the base of the Left pulmonary artery
heart ● Takes deoxygenated blood from the pulmonary trunk and
● The right and left ventricles extend from the base of the transports it to the left lung where the blood vessel then
heart branches into the lungs and gas exchange takes place,
● The superior and inferior venae cavae enter the right re-oxygenating the blood.
atrium Pulmonary trunk
● The pulmonary veins enter the left atrium ● 5 cm in length and 3 cm in diameter
● The pulmonary trunk exits the right ventricle ● Branches into 2 pulmonary arteries (Left and right
● The aorta exits the left ventricle pulmonary arteries)

Left pulmonary veins

● Blood vessels that transfer freshly oxygenated blood
from the left lung to the left atria of the heart
Left atrium
● Receives oxygen-rich blood from the lungs and pumps it
to the left ventricle
Great cardiac vein
● Starting from the apex of the heart and running parallel
with the anterior interventricular artery
● Returns deoxygenated blood (metabolic waste products)
from the anterior surfaces of the left ventricle
Anterior interventricular vein
● Courses anteriorly in between the left and right ventricle
Left ventricle
Superior vena cava and Inferior vena cava ● Pumps the oxygen-rich blood to the body
● Carry blood from the body to the right atrium
Aorta
● Arising from the left ventricle
● Largest artery in the body

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 PBS 2 (2018): HUMAN PHYSIOLOGY AND PATHOPHYSIOLOGY
Institute of Pharmacy S.Y. 2022 - 2023
1st Year I 2st Semester I Finals
Prof. Joshua Kenneth Ng

Heart Chambers and Internal Anatomy ● These valves allow blood to flow from the atria into the
● The heart is a muscular pump consisting of four ventricles but prevent it from flowing back into the atria.
chambers mainly: the right and left atria, and the right When the ventricles relax, the higher pressure in the atria
and left ventricles. forces the AV valves to open, and blood flows from the
atria into the ventricles. In contrast, when the ventricles
Right and Left Atria contract, blood flows toward the atria and causes the AV
● Blood enters the atria of the heart through blood vessels valves to close.
called veins. The atria function primarily as reservoirs,
where blood returning from veins collects before it enters Each ventricle contains cone-shaped, muscular pillars called
the ventricles. Contraction of the atria forces blood into papillary (pap′ĭ-lār-ē) muscles. These muscles are attached by thin,
the ventricles to complete ventricular filling. strong, connective tissue strings called chordae tendineae (kōr′dē
● The right atrium receives blood from three major ten′di-nē-ē; heart strings) to the free margins of the cusps of the
openings: (1) the superior vena cava, (2) the inferior vena atrioventricular valves. When the ventricles contract, the papillary
cava, and (3) the coronary sinus. The superior vena cava muscles contract and prevent the valves from opening into the
and the inferior vena cava drain blood from most of the atria by pulling on the chordae tendineae attached to the valve
body, and the smaller coronary sinus drains blood from cusps).
most of the heart muscle.
● The left atrium receives blood through the four SEMILUNAR VALVE
pulmonary veins, which drain blood from the lungs. ● located between each ventricle and its associated great
● The two atria are separated from each other by a artery.
partition called the interatrial (between the atria) septum. ● The pulmonary semilunar valve is located between the
Right and Left Ventricles right ventricle and the pulmonary trunk, and the aortic
● The ventricles of the heart are its major pumping semilunar valve is located between the left ventricle and
chambers. aorta.
● They eject blood into the arteries and force it to flow ● Each valve consists of three pocketlike semilunar
through the circulatory system. (half-moon-shaped) cusps. When the ventricles relax, the
● The atria open into the ventricles, and each ventricle has pressures in the aorta and pulmonary trunk are higher
one large outflow route located superiorly near the than in the ventricles. Blood flows back from the aorta or
midline of the heart. pulmonary trunk toward the ventricles and enters the
● The right ventricle pumps blood into the pulmonary trunk, pockets of the cusps, causing them to bulge toward and
and the left ventricle pumps blood into the aorta. The two meet in the center of the aorta or pulmonary trunk, thus
ventricles are separated from each other by the muscular closing the vessels and blocking blood flow back into the
interventricular (between the ventricles) septum. ventricles. When the ventricles contract, the increasing
● The wall of the left ventricle is thicker than the wall of the pressure within the ventricles forces the semilunar valves
right ventricle, and the wall of the left ventricle contracts to open.
more forcefully and generates a greater blood pressure
than the wall of the right ventricle. When the left ventricle A plate of connective tissue, sometimes called the cardiac
contracts, the pressure increases to approximately 120 skeleton, or fibrous skeleton, consists mainly of fibrous rings that
mm Hg. When the right ventricle contracts, the pressure surround the atrioventricular and semilunar valves and give them
increases to approximately one-fifth of the pressure in solid support. This connective tissue plate also serves as electrical
the left ventricle. However, the left and right ventricles insulation between the atria and the ventricles and provides a rigid
pump nearly the same volume of blood. The higher attachment site for cardiac muscle.
pressure generated by the left ventricle moves blood
through the larger systemic circulation, whereas the Route of Blood Flow Through the Heart
lower pressure generated by the right ventricle moves
blood through the smaller pulmonary circulation

Heart Valves
● The one-way flow of blood through the heart chambers is
maintained by heart valves. There are two types of heart
valves: atrioventricular valves and semilunar valves.
ATRIOVENTRICULAR VALVE:
● Located between each atrium and ventricle.
● Specifically, the AV valve between the right atrium and
the right ventricle has three cusps and is called the
tricuspid valve.
● The AV valve between the left atrium and the left
ventricle has two cusps and is called the bicuspid valve
or mitral (resembling a bishop’s miter, a two-pointed hat)
valve.

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 PBS 2 (2018): HUMAN PHYSIOLOGY AND PATHOPHYSIOLOGY
Institute of Pharmacy S.Y. 2022 - 2023
1st Year I 2st Semester I Finals
Prof. Joshua Kenneth Ng

2. Intercalated disks
● highly folded, and the adjacent cells fit together, greatly
increasing contact between them and preventing cells
from pulling apart
3. Gap junction
● Specialized cell membrane structures in the intercalated
disk that ) allow cytoplasm to flow freely between cells.

ELECTRICAL ACTIVITY OF THE HEART

● Blood enters the right atrium from the systemic
circulation, which returns blood from all the tissues of Conduction System of the Heart
the body. 1. Sinoatrial (SA) node
● Blood flows from an area of higher pressure in the ● functions as the heart’s pacemaker, is located in the
systemic circulation to the right atrium, which has a superior wall of the right atrium and initiates the
lower pressure. contraction of the heart
● Most of the blood in the right atrium then passes into the 2. Atrioventricular (AV) node
right ventricle as the ventricle relaxes following the ● located in the lower portion of the right atrium
previous contraction. 3. Atrioventricular (AV) bundle
● The right atrium then contracts, and most of the blood ● bundle of specialized cardiac muscle
remaining in the atrium is pushed into the ventricle to 4. Purkinje fibers
complete right ventricular filling. ● composed of specialized cardiac muscle fibers that
● Contraction of the right ventricle pushes blood against conduct action potentials more rapidly than do other
the tricuspid valve, forcing it closed, and against the cardiac muscle fibers.
pulmonary semilunar valve, forcing it open, thus allowing
blood to enter the pulmonary trunk.
Conduction System of the Heart Process
● The pulmonary trunk branches to form the pulmonary
● Action potentials originate in the sinoatrial (SA) node and
arteries.
travel across the wall of the atrium (arrows) from the SA
● Blood returning from the lungs enters the left atrium
node to the atrioventricular (AV) node.
through the four pulmonary veins.
● Action potentials pass through the AV node and along
● The blood passing from the left atrium to the left
the atrioventricular (AV) bundle, which extends from the
ventricle opens the bicuspid valve, and contraction of the
AV node, through the fibrous skeleton, into the
left atrium completes left ventricular filling.
interventricular septum.
● Contraction of the left ventricle pushes blood against the
● The AV bundle divides into right and left bundle branches,
bicuspid valve, closing it, and against the aortic
and action potentials descend to the apex of each
semilunar valve, opening it and allowing blood to enter
ventricle along the bundle branches.
the aorta.
● Action potentials are carried by the Purkinje fibers from
● Blood flowing through the aorta is distributed to all parts
the bundle branches to the ventricular walls.
of the body, except to the parts of the lungs supplied by
the pulmonary blood vessels.
Action Potentials in Cardiac Muscle
HISTOLOGY OF THE HEART 1. Depolarization phase
● Na+ channels open.
Heart Wall
● Ca2+ channels open.
Three layers of tissue in the Heart Wall
2. Plateau phase
1. Epicardium (visceral pericardium)
● Na+ channels close.
● a thin, serous membrane forming the smooth outer
● Some K+ channels open, causing repolarization.
surface of the heart
● Ca2+ channels are open, producing the plateau by
2. Myocardium
slowing further repolarization.
● The thick, middle layer of the heart that is composed of
3. Repolarization phase
cardiac muscle cells and is responsible for contraction of
● Ca2+ channels close.
the heart chambers
● Many K+ channels open.
3. Endocardium
4. Refractory period effect on tension
● allows blood to move easily through the heart
● Cardiac muscle contracts and relaxes almost completely
during the refractory period (purple shaded area).
Cardiac Muscle cells
● Elongated, branching cells that contain one, or
occasionally two, centrally located nuclei
1. Actin and myosin myofilaments
● responsible for muscle contraction, and their
organization gives cardiac muscle a striated (banded)
appearance

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 PBS 2 (2018): HUMAN PHYSIOLOGY AND PATHOPHYSIOLOGY
Institute of Pharmacy S.Y. 2022 - 2023
1st Year I 2st Semester I Finals
Prof. Joshua Kenneth Ng

Electrocardiogram
Action potentials conducted through the heart during the cardiac
cycle produce electrical currents that can be measured at the CARDIAC CYCLE
surface of the body ● Refers to the repetitive pumping process that begins with
● The normal ECG consists of a P wave, a QRS complex, the onset of cardiac muscle contraction and ends with
and a T wave the beginning of the next contraction
○ P wave ● Pressure changes produced within the heart chambers
■ results from depolarization of the as a result of cardiac muscle contraction move blood
atrial myocardium from areas of higher pressure to areas of lower pressure
○ T wave ○ PRIMER PUMP - Atrium
■ represents repolarization of the ○ POWER PUMP - Ventricles
ventricles
○ QRS complex Atrial Systole
1. Q wave - corresponds to depolarization of the interventricular ● refers to contraction of the two atria.
septum Ventricular Systole
2. R wave - produced by depolarization of the main mass of the ● refers to contraction of the two ventricles
ventricles Atrial DIastole
3. S wave - represents the last phase of ventricular depolarization ● refers to relaxation of the two atria
at the base of the heart Ventricular Diastole
PQ interval/ PR interval ● refers to relaxation of the two ventricles.
● time between the beginning of the P wave and the
beginning of the QRS complex CARDIAC CYCLE
QT interval 1. The atria and ventricles are relaxed. AV valves open, and blood
● represents the length of time required for ventricular flows into the ventricles. The ventricles fill to approximately 70% of
depolarization and repolarization their volume.
2. Atrial systole - The atria contract and complete ventricular filling
3. Ventricular systole - Contraction of the ventricles causes
pressure in the ventricles to increase. Almost immediately, the AV
valves close (the first heart sound). The pressure in the ventricles
continues to increase
4. Continued ventricular contraction causes the pressure in the
ventricles to exceed the pressure in the pulmonary trunk and aorta.
As a result, the semilunar valves are forced open, and blood is
ejected into the pulmonary trunk and aorta.

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 PBS 2 (2018): HUMAN PHYSIOLOGY AND PATHOPHYSIOLOGY
Institute of Pharmacy S.Y. 2022 - 2023
1st Year I 2st Semester I Finals
Prof. Joshua Kenneth Ng

5. Ventricular diastole - At the beginning of ventricular diastole, the

ventricles relax, and the semilunar valves close (the second heart
sound)
6. As diastole continues, the pressure continues to decline in the
ventricles until atrial pressures are greater than ventricular
pressures. Then the AV valves open, and blood flows directly from The heart rate and stroke volume would vary depending on the
the atria into the relaxed ventricles. During the previous ventricular person. Athletes tend to have a
systole, the atria were relaxed and blood collected in them. When higher stroke volume and lower heart rate at rest because exercise
the ventricles relax and the AV valves open, blood flows into the has increased the size of
ventricles (figure 12.17, step 1) and they begin to fill again their hearts. Nonathletes are more likely to have a higher heart rate
and lower stroke volume.
HEART SOUNDS For example, during exercise, the heart rate in a non-athlete can
Pulmonary Semilunar Valve increase to 190 bpm, and the
● allowing the unidirectional blood flow from the right stroke volume to 115 mL/beat. Therefore, the cardiac output
ventricle to the pulmonary artery and then to the lungs. increases to approximately 22 L/min:
Aortic Semilunar Valve
● allows the unidirectional blood flow from the left ventricle
to the aorta and then to the rest of the body.
Bicuspid Valve
● this valve has two leaflets. They allow blood to flow from
the lungs into the left atrium.
Tricuspid Valve The cardiac output is several times greater than the cardiac output
● this valve has three leaflets. They allow blood to flow under resting conditions. Athletes can increase their cardiac to a
from the right atrium to the right ventricle. greater degree than non-athletes. The control mechanisms that
modify the stroke volume and the heart rate are classified as
ABNORMALITIES IN HEART VALVES intrinsic and extrinsic.
Incompetent Valve
● a heart valve does not close completely INTRINSIC REGULATION OF THE HEART
Murmurs Intrinsic regulation
● abnormal heart sounds due to faulty valves ● refers to the mechanism contained within the heart itself.
Stenosed The force of contraction produced by cardiac muscle is
● narrowed opening of the valve. related to the degree of stretch of cardiac muscle fibers.
The amount of blood in the ventricles at the end of the
REGULATION OF HEART FUNCTION ventricular diastole determines the degree to which
There are various measurements that can be taken to access the cardiac muscle fibers are stretched.
heart’s function. But first, we must identify how the Cardiac Output Preload
can be calculated. ● is the degree to which the ventricular walls are stretched
Cardiac Output (CO) at the end of diastole.
● is the volume of blood pumped by either ventricle of the Venous Return
heart each minute. ● is the amount of blood that returns to the heart.
Stroke Volume (SV) ● If venous return increases, it causes the heart to fill to a
● is the volume of blood pumped per ventricle each time greater volume and strains the cardiac muscle fibers
the heart contracts. increasing preload. Cardiac muscle fibers then contract
Heart Rate (HR) more forcefully. A larger stroke volume results from the
● is the number of times the heart contracts each minute. heart's ability to contract with greater force, which expels
The formula: an increased volume amount of blood. Cardiac output
rises as venous return rises, causing a rise in preload. On
the other hand, if venous return falls, the preload falls and
the cardiac output falls.
Starling’s Law of the Heart
● is the relationship between preload and stroke volume.
Because venous return is influenced by many conditions,
Starling’s Law of the Heart has a major influence on the
For example, under resting conditions, the heart rate is cardiac output.
approximately 72 beats/min, and the stroke volume is Afterload
approximately 70 mL/beat. Consequently, the cardiac output is ● refers to the pressure against which the ventricles must
slightly more than 5 L/min: So, if one calculates it, it would be pump blood.
something like this: ● People suffering from hypertension have an increased
afterload because their aortic pressure is elevated during
contraction of the ventricles.

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 PBS 2 (2018): HUMAN PHYSIOLOGY AND PATHOPHYSIOLOGY
Institute of Pharmacy S.Y. 2022 - 2023
1st Year I 2st Semester I Finals
Prof. Joshua Kenneth Ng

● A reduced afterload decreases the work the heart must ● The figure shows how the baroreceptor reflex keeps the
do. People who have lower blood pressure have a heart rate and stroke volume within normal ranges. So
reduced afterload and develop heart failure less often when the blood pressure increases, the baroreceptors are
than people who have hypertension. stimulated. Action potentials are sent along the nerve
EXTRINSIC REGULATION OF THE HEART fibers to the medulla oblongata at increased frequency.
Extrinsic regulation ● This prompts the cardioregulatory center to increase
● refers to the mechanisms external to the heart, such as parasympathetic stimulation and decrease sympathetic
either nervous or chemical regulation. stimulation of the heart. As a result, the heart rate and
Nervous Regulation: Baroreceptor Reflex stroke volume decrease, causing blood pressure to
● Nervous influences of heart activity are carried through decline.
the autonomic nervous system. Both sympathetic and Chemical Regulation: Chemoreceptor Reflex
parasympathetic nerve fibers innervate the heart and ● Epinephrine and small amounts of norepinephrine
have a major effect on the SA node. released from the adrenal medulla in response to
● Stimulation by sympathetic nerve fibers causes the heart exercise, emotional excitement, or stress also influence
rate and the stroke volume to increase, whereas the heart’s function.
stimulation by parasympathetic nerve fibers causes the ● Excitement, anxiety, or anger can affect the
heart rate to decrease. cardioregulatory center, resulting in increased
Baroreceptor reflex sympathetic stimulation of the heart and increased
● (baro, meaning pressure) is a mechanism of the nervous cardiac output.
system that plays an important role in regulating heart ● Depression, on the other hand, can increase
function. parasympathetic stimulation of the heart, causing a
Baroreceptors slight reduction in cardiac output.
● are stretch receptors that monitor blood pressure in the
aorta and in the wall of the internal carotid arteries, CHEMORECEPTOR REFLEX
which carry blood to the brain.
● The action potentials are transmitted along nerve fibers
from the stretch receptors to the medulla oblongata of
the brain.
Cardioregulatory center
● Within the medulla oblongata, it receives and integrates
action potentials from the baroreceptors. The
cardioregulatory center controls the action potential
frequency in sympathetic and parasympathetic nerve
fibers that extend from the brain and spinal cord to the
heart.
Epinephrine and norepinephrine, released from the adrenal gland,
increase the stroke volume and heart rate.

BARORECEPTOR REFLEX

● The medulla oblongata of the brain also contains

chemoreceptors that are sensitive to changes in pH and
CO2 levels. A decrease in pH, often caused by an
increase in CO2, results in sympathetic stimulation of the
heart.

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 PBS 2 (2018): HUMAN PHYSIOLOGY AND PATHOPHYSIOLOGY
Institute of Pharmacy S.Y. 2022 - 2023
1st Year I 2st Semester I Finals
Prof. Joshua Kenneth Ng

SUMMARY OF EXTRINSIC REGULATION Angiography

● is a type of x-ray used to check the blood vessels. It
produces the angiogram which is the picture of blood
vessel that is usually obtained by injecting the blood
vessel with dye that can be detected by x-rays.

● This figure summarizes how nervous and chemical

factors interact to regulate the heart rate and stroke
volume.

ADDITIONAL INFORMATION
● Changes in the extracellular concentration of K+, Ca2+,
and Na+, which influence other electrically excitable
SYMPTOMS OF MYOCARDIAL INFARCTION
tissues, also affect cardiac muscle function.
● Chest pain that radiates down left arm
● An excess of extracellular K+ causes the heart rate and
● Tightness and pressure in chest
stroke volume to decrease.
● Difficulty breathing
● If the extracellular K+ concentration increases further,
● Nausea and vomiting
normal conduction of action potentials through cardiac
● Dizziness and fatigue
muscle is blocked, and death can result.
● An excess of extracellular Ca2+ causes the heart to
TREATMENTS FOR MYOCARDIAL INFARCTION
contract arrhythmically. Reduced extracellular Ca2+
● Restore blood flow to cardiac muscle
causes both the heart rate and stroke volume to
● Medication to reduce blood clotting (aspirin) and
decrease.
increase blood flow
● Body temperature affects the metabolism in the heart
● Supplemental O2 to restore normal O2 to heart tissue
just as it affects other tissues. Elevated body
● Prevention and control of hypertension
temperature increases the heart rate, and reduced body
● Angioplasty or bypass surgery
temperature slows the heart rate.
Angioplasty
EFFECTS OF AGING ON THE HEART
The following age-related changes are common:
1. By age 70, cardiac output has often decreased by one-third.
2. Hypertrophy of the left ventricle can cause pulmonary edema.
3. Decrease in the maximum heart rate of 30–60% by age 85 leads
to decreased cardiac output.
4. The aortic semilunar valve can become stenotic or incompetent.
5. Coronary artery disease and congestive heart failure can
develop.
6. Aerobic exercise improves the functional capacity of the heart at
all ages

MYOCARDIAL INFARCTION
Heart attack
● medically known as a myocardial infarction, is a fatal
medical emergency in which your heart muscle begins to
die due to a lack of blood flow. This is usually caused by
a blockage in the arteries that supply blood to your heart.
Furthermore, if not restored quickly by a healthcare ENDOCARDITIS
provider or first aid, it can cause permanent heart ● It is the inflammation of the endocardium; affects the
damage or even worse, the patient could die. valves more severely than other areas of the
endocardium; may lead to scarring, causing stenosed or

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 PBS 2 (2018): HUMAN PHYSIOLOGY AND PATHOPHYSIOLOGY
Institute of Pharmacy S.Y. 2022 - 2023
1st Year I 2st Semester I Finals
Prof. Joshua Kenneth Ng

incompetent valves.
Common symptoms of endocarditis include:
● Aching joints and muscles
● Chest pain when you breathe
● Fatigue
● Flu-like symptoms, such as fever and chills
● Night sweats
● Shortness of breath
● Swelling in the feet, legs or belly
● A new or changed whooshing sound in the heart
(murmur)
Less common endocarditis symptoms can include:
● Unexplained weight loss
● Blood in the urine
● Tenderness under the left rib cage (spleen)
● Painless red, purple or brown flat spots on the soles
bottom of the feet or the palms of the hands (Janeway
lesions)
● Painful red or purple bumps or patches of darkened skin
(hyperpigmented) on the tips of the fingers or toes (Osler
nodes)
● Tiny purple, red or brown round spots on the skin
(petechiae), in the whites of the eyes or inside the mouth

Pathophysiology
At least three critical elements are involved in the pathophysiology
of infective endocarditis:
1. preparation of the cardiac valve for bacterial adherence,
2. adhesion of circulating bacteria to the prepared valvular surface,
and
3. survival of the adherent bacteria on the surface, with
propagation of the infected vegetation.

Treatment
● Ampicillin + gentamicin + flucloxacillin or oxacillin
● Vancomycin + gentamicin (if PCN allergic) Causes
● Vancomycin + gentamicin + rifampin if early prosthetic
valve endocarditis (under one year) or
healthcare-associated endocarditis
● Surgery (when the heart failure is progressive)

CARDIOMYOPATHY
● Cardiomyopathies are a mixed group of diseases of the
myocardium (cardiac muscle) defined by structural or
functional abnormalities that negatively affect the pump
function of the heart. In some types, there is obstruction
to the outflow of blood during the cardiac cycle
● “a heterogeneous group of diseases of the myocardium
associated with mechanical and/or electric dysfunction
that usually (but not invariably) exhibit inappropriate Treatments and medications
ventricular hypertrophy or dilatation due to a variety of 1. Medicines to remove extra sodium and fluid from your body:
etiologies that are frequently genetic. Cardiomyopathies ● These include diuretics and aldosterone antagonists.
are either confined to the heart or part of generalised These medicines lower the amount of blood that the
systemic disorders and often lead to cardiovascular heart must pump.
death or progressive heart failure-related disability” - 2. Blood pressure medications
American Heart Association ● These include angiotensin converting enzyme (ACE)
inhibitors, angiotensin II receptor blockers, and
combination hydralazine/isosorbide dinitrate

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3. Medicines to slow your heart rate CARDIOMYOPATHY

● such as beta blockers, calcium channel blockers, and Treatment and Medications
ivabradine 1. Cholesterol drugs
● These medicines make it easier for your heart to pump ● Medications can help lower bad cholesterol and reduce
blood. plaque buildup in the arteries. Such drugs include:
4. Medicines to balance your electrolyte levels: ○ Statins
● These can help your heart work better. Side effects ○ Niacin
include kidney disease and high potassium levels in your ○ Fibrates
blood. ○ Bile acid sequestrants
5. Blood thinners (anticoagulants): 2. Aspirin
● These medicines help prevent blood clots. The ● Aspirin helps then the blood and prevent blood clots.
medicines can raise your risk of serious bleeding. Daily low-dose aspirin therapy may be recommended for
6. Digoxin (Lanoxin) the primary prevention of heart attack or stroke in some
● This is used to treat a fast or irregular heartbeat. Digoxin people.
can cause nausea, vomiting, and diarrhea. It may also ● Daily use of aspirin can have serious side effects,
cause some types of arrhythmias. including bleeding in the stomach and intestines. Which
7. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors: is why patients should not start taking a daily aspirin
● These medicines are often used to treat diabetes but can without talking to health care provider.
also help your heart work better. Possible side effects 3. Beta blockers
include kidney disease and infections. ● These drugs slow the heart rate. They also lower blood
pressure. If someone has had a heart attack, beta
Physiology blockers may reduce the risk of future attacks.
● Reduces the amount of blood the coronary arteries can ● They are recommended for the first-line treatment of
deliver to the myocardium heart failure, coronary artery disease, and atrial
● It is the most common type of heart disease fibrillation. They work mainly by decreasing the activity of
● It is caused by a plaque buildup in the walls of the the heart by blocking the action of hormones like
arteries that supply blood to the heart and other parts of adrenaline.
the body ○ Atenolol (Tenormin)
○ Bisoprolol (Zebeta)
Pathophysiology ○ Carvedilol (Coreg)
1. Formation of a fatty streak ○ Labetalol
2. Cholesterol, fats, lipoproteins, and other debris accumulate at ○ Metoprolol
the site of vascular damage or in the intima of the artery ○ Propanolol (Inderal)
3. High concentration of low-density lipoprotein (LDL) penetrate ○ Timolol
the damaged endothelium and undergo oxidation. 4. Calcium channel blockers
4. The altered LDL acts as a beacon that attracts leukocytes to ● One of these drugs may be recommended if a patient
migrate towards the vessel wall can’t take beta blockers or beta blockers don’t work on
5. Macrophages appear, engulf the lipoproteins, and become foam them.
cells which give rise to fatty streak ● Calcium channel blockers are vasodilators and can help
6. Once the fatty streak is formed, it then attracts the smooth improve symptoms of chest pain, arrhythmia, and help
muscle cells to the site, where they multiply and start to produce control high blood pressure.
extracellular matrix comprising of collagen and proteoglycan. ○ Amlodipine (Norvasc)
7. The fibrous plaque starts to support itself. It develops its own ○ Diltiazem (Cardiazem)
small vessels to provide it with a supply of blood in a process ○ Felodipine (Plendil)
called angiogenesis. ○ Nifedipine XL (Adalat XL)
8. Plaques calcify and the final plaque is now made up of a cap of
fibrous tissue covering a core that is rich in lipids as well as 5. Angiotensin-converting enzyme (ACE) inhibitors and
necrotic or dead cells angiotensin II receptor blockers (ARBs)
9. Exposure, due to rupture, of underlying core of lipids and ● These medicines lower blood pressure and may help
necrotic material to thrombogenic factors in blood can cause keep coronary artery disease from getting worse
aggregation of platelets that forms clots. ● ACE inhibitors prevent an enzyme in the body from
10. As the deposits on the plaques grow in size and dimension, the producing angiotensin II, a substance known for
blood vessels become further narrowed and there may be vasoconstriction. On the other hand, ARBs antagonize
obstruction leading to a heart attack or a myocardial infarction. the receptor binding of angiotensin II to AT1 receptors.
● ACE INHIBITORS
○ Benazepril (Lotensin)
○ Captopril (Capoten)
○ Enalapril/Enalaprilat (Vasotec oral and
injectable)
● ARBS

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○ Losartan effectiveness
○ Irbesartan ● ATRIAL SEPTAL DEFECT
○ Varlsartan ○ is a hole in the wall between the heart’s two
○ Candesartan upper chambers. ASD is a congenital condition,
6. Nitroglycerin which means it is present at birth.
● This medicine widens the heart arteries and can help ● VENTRICULAR SEPTAL DEFECT
control or relieve chest pain ○ is a hole in the wall between the two lower
● Available as a pill, spray, or patch chambers. In children, a VSD is usually
7. Ranolazine congenital.
● This medication may help people with chest pain
(angina) Symptoms of septal defects in babies include:
● May be prescribed with or instead of a beta blocker ● Abnormal heartbeat
● Anti-anginal ● Fast breathing
● Poor growth
CORONARY THROMBOSIS ● Trouble eating
Physiology In older children and adults, symptoms can include:
● Formation of blood clot in a coronary artery ● Fatigue
● Coronary thrombosis and coronary heart disease aren’t ● Heart palpitations
the same but they are almost in very similar conditions ● Inability to exercise
● It usually occurs due to rupture or erosion of preexisting ● Shortness of breath
coronary artery plaques discussed earlier in coronary ● Stroke
heart disease. Pathophysiology
Pathophysiology ● Flow across the defect occurs in both systole and
● Plaque rupture is the most frequent cause of thrombosis. diastole. In most patients, flow is predominantly left to
In plaque rupture, a structural defect – a gap – in the right, but transient right-to-left shunts are common,
fibrous cap exposes the highly thrombogenic core to the particularly with isometric strain. The bulk of the shunt
blood. flow occurs during diastole. In this phase, blood in each
● Plaque rupture occurs where the cap is thinnest and atrium has 2 alternative pathways: following the normal
most infiltrated by foam cells (macrophages). The route through the AV valve to the ventricle on that side or
weakest spot is often the cap margin or should region, passing through the ASD to fill the opposite ventricle. The
and only extremely thin fibrous caps are at risk of direction of flow across the ASD during diastole is
rupturing. determined by the instantaneous differences in the
● Thinning of the fibrous cap involves the gradual loss of compliance and the capacity of the 2 ventricles.
smooth muscle cells from the fibrous cap. Ruptured caps Treatment and Medications
contain fewer SMCs and less collagen than intact caps, TRANSCATHETER REPAIR
and SMCs are usually absent at the actual site of rupture. ● A transcatheter repair, also called transcatheter device
At the same time, infiltrating macrophages degrade the closure, is usually recommended for an atrial septal
collagen-rich cap matrix. defect.
● Ruptured caps are heavily infiltrated by macrophage ● During this procedure, a pediatric interventional
foam cells as the underlying core of lipids and necrotic cardiologist makes an incision in the groin, inserts a
material is exposed to thrombogenic factors in the blood catheter, and funnels a small mesh patch through the
● This causes the aggregation of platelets that form a clot catheter and up to the hole in the heart.
across the plaque and further narrow the artery. From OPEN HEART SURGERY
this, blood clots are formed ● A ventricular septal defect is usually repaired with an
Treatment and Medications open surgery, though some children may be candidates
● If a doctor suspects you have a coronary thrombosis, for a less invasive procedure. During open VSD surgery,
they may immediately give you aspirin the surgeon accesses the heart by opening the sternum
● A cardiac catheter, also known as a balloon angioplasty, (breastbone). A patch is applied to the septal defect. As
can open the artery backup to restore normal blood flow with a transcatheter repair, the heart’s own tissue
to heart eventually grows over the patch. Open heart surgery is
● Smaller clots may be treated more easily with a stent also necessary for ASD that cannot be repaired with a
● Some patients may also need to have medications to transcatheter device.
dissolve a clot. Anticoagulants are medications that thin
the blood and help dissolve blood clots PATENT DUCTUS ARTERIOSUS
Patent ductus arteriosus, or PDA, is a heart defect that can develop
SEPTAL DEFECT soon after birth. It affects the way blood flows through a baby’s
Physiology lungs. PDA occurs when the opening between the aorta (the artery
● Hole in the septum between the left and right sides of the that carries oxygen-rich blood to the body) and the pulmonary
heart, allowing blood to flow from one side of the heart to artery (the artery that carries oxygen-poor blood to the lungs) does
the other and greatly reducing the heart’s pumping not close as it should.

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recovery time. During this procedure, a pediatric heart

Symptoms of PDA depend on the size of the opening between a surgeon:
baby’s aorta and pulmonary artery. If the opening is small, baby ○ Makes an incision in the chest
may not have symptoms. But a larger opening may cause ○ Closes the connection with stitches or small
symptoms such as: metal clips
● Fast or hard breathing
● Frequent respiratory infections IMMUNITY AND IMMUNIZATION (LAB)
● Heart murmur (a “whooshing” sound made by abnormal THE BODY DEFENSES AND FIGHTING INFECTION
blood flow through the heart) ● The human body has multiple defense mechanisms that
● Poor weight gain work together to provide resistance, which is the ability to
● Trouble feeding or tiredness while feeding fight disease, illness, and infection.
Pathophysiology ● An infection may be caused by the presence and
● It involves several complex physiological changes. multiplication of a disease-causing agent or pathogen,
Normally, the ductus arteriosus closes shortly after birth which can be a virus, bacterium, fungus, or protozoan.
because of increased oxygen levels and decreased
prostaglandin levels in the body. In infants with PDA, 2 GENERAL CATEGORIES OF BODY DEFENSES
however, the ductus remains open, allowing oxygen-rich
1. Innate (nonspecific) defense
blood from the aorta to mix with oxygen-poor blood from
2. Adaptive (specific) Defenses
the pulmonary artery.
Innate (nonspecific) defense
● This results in an increased volume of blood flowing
through the pulmonary circulation, leading to pulmonary ● Defends against many different types of pathogens.
congestion, increased pulmonary artery pressure, and ● This type of defense, which is present at birth, includes:
ultimately, pulmonary hypertension. The left ventricle ○ mechanical barriers
may also become enlarged due to the increased volume ○ chemical barriers
of blood it must pump, leading to left ventricular ○ NK cells
hypertrophy. ○ inflammation
● The abnormal blood flow and pressure changes in the ○ Phagocytosis
heart can also lead to several other complications, such ○ Fever
as aortic dilation, endocarditis (infection of the heart ○ species resistance.
valves), and congestive heart failure. ● Innate or nonspecific defenses prevent or limit
Treatment and Medications microorganisms and other environmental hazards from
Indomethacin: approaching, entering, or spreading.
● Indomethacin is typically given to premature infants with ● These defenses are often able to prevent infection by
PDA who are less than 32 weeks gestational age and destroying pathogens, without needing the help of any
have a birth weight of less than 1,500 grams. It is usually other defenses.
administered intravenously or orally over a course of 2-3 ● Sometimes, however, the adaptive immune system is
days, during which time the infant's condition is closely needed to assist the nonspecific defenses.
monitored for any adverse effects. ● Nonspecific defenses are the first line of defense and
Ibuprofen: include the skin and mucosa.
● Ibuprofen has been shown to have a similar efficacy and ● When pathogens penetrate the skin or mucosa, the
safety profile to indomethacin in the treatment of PDA, second line of defense is activated.
with some studies suggesting that it may have a lower ○ Relies in Internal defenses including microbial
risk of adverse effects such as gastrointestinal bleeding protein and phagocytes
and renal dysfunction. Ibuprofen is typically administered ● Inflammation - is the most important process in the
over a course of 3-4 days, with dosages adjusted based second line of defense.
on the infant's weight and renal function. ○ The nonspecific defenses are classified as
Cardiac catheterization mechanical barriers, which cover body
● Catheterization is the most common treatment for PDA. surfaces, and chemical substances, which are
During this minimally invasive procedure, a pediatric involved with invading pathogens.
interventional cardiologist: Mechanical Barrier
○ Makes a tiny incision near a large blood vessel ● Physical barrier
in the leg ● Mechanical barriers include the skin and the mucous
○ Inserts a catheter (thin, flexible tube) into the membranes that line the respiratory system, digestive
blood vessel and threads it up to the PDA system, urinary system, basement membranes, and
○ Slides a coil or other plug-like device through reproductive passageways. They protect against certain
the catheter and into the PDA to close it infectious agents.
Patent ductus arteriosus surgery ● The body’s hair, sweat, and mucus also act as
● Patent ductus arteriosus surgery is usually reserved for mechanical barriers. The mechanical barriers of
babies with very large PDAs. Open surgery presents more immunity are ready to act when we are born.
risks than cardiac catheterization and requires a longer

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Mechanical Barrier of Skin vs. Infection

● The skin’s keratinized epithelial membrane stops most Additional Info:
microorganisms on the skin from penetrating it. ● Contains at least 20 special compliments (C-proteins)
○ Found in stratum corneum/ horny layer ○ C1-C9 Factors
● Keratin itself resists many weak bases and acids as well ● Complement - refers to how the system complements
as toxins and bacterial enzymes. Inside the body, the the action of the antibodies
mucous membranes function in much the same capacity. ○ Complement proteins interact in chains of
reaction or cascades that are similar to blood
Additional info: clotting systems; once complement proteins
● Natural microbiome - Staphylococcus aureus are activated, they are capable of acting as
○ Only becomes dangerous once the immune lysing (burst contents of bacteria and viruses
system is weak and killing certain cells and bacteria). There are
○ It can produce systemic infection additional chemical barriers in the respiratory
● The skin contains keratin that resists many weak bases tract mucosae.
and acids as well as toxins and bacterial enzymes. Inside ○ When microorganisms make it past the
the body, the mucous membrane is a protective lining in chemical barrier, the internal innate defense
the digestive, urinary and respiratory system begins to combat them.
○ The mucous wards away pathogens away from
the organ to avoid certain infections Involves the classical pathway and the alternative
Chemical Barrier pathway.
● Provided by enzymes and other chemical substances in 1. Classical pathway
body fluids, these include pepsin and hydrochloric acid in ○ is the fastest and most effective pathway,
the stomach; tears; lysozyme in tears, saliva, breast milk, beginning with binding of complement protein
and mucus; salt in perspiration produced in your sweat C1 to an antibody, already attached to its
glands specific antigen, which may be a bacterial cell
○ pepsin and hydrochloric acid helps churn out wall.
food ○ When antibody molecules are absent, the
■ Churn- from solid food to liquid food alternative or properdin pathway activates the
Antimicrobial proteins complement system.
Interferons 2. Alternative pathway
● secreted by infected cells and diffuse to nearby cells, ○ also ends, like the classical pathway, with
stimulating protein synthesis that interferes with viral conversion of inactive C3 protein into activated
replication. C3b protein.
Additional info: ○ The activation of complement results in
● Small proteins that bind to an infected cell and stimulate formation of pores, increased phagocytosis,
them to make protective proteins and release of histamine which can cause
● ARE NOT VIRUS SPECIFIC inflammation.
● Used for treatment of various kinds of viral infections Acid-Mantle Components
● MOA: blocks viral RNA from synthesizing proteins and ● inhibit bacterial growth. These consist of the acidity of
degrades viral RNA itself. the skin, stomach secretions, and vagina.
Three Types of Interferon ○ The skin and vagina have certain pH to protect
1. Interferon-A (Alpha) the barrier of the skin which inhibit bacterial
● Activates NK cells growth.
2. Interferon-B (Beta) Mucin
● Activates NK cells ● a substance that forms mucus when dissolved in water.
3. Interferon-Y (Gamma) ● Mucus
● Immune interferon secreted by WBC that activates ○ Thick and sticky found in the lining of the
macrophage that has a wide range of immune passageway of the digestive and respiratory
mobilization effects. system
Complement Proteins ○ Trap variety of organisms
● a group of proteins in plasma and other body fluids that ● Mucin of saliva traps microorganisms but washes them
interact to cause inflammation and phagocytic activities. from the mouth to the stomach where they are digested
● The term complement refers to the way this system Dermcidin
“complements” the action of antibodies. ● found in eccrine sweat is toxic to bacteria, like the effects
● Complement proteins interact in chains or reactions or of certain lipids in the body’s sebum.
cascades of that similar to the blood clotting system. Defensins
● Activated complement also acts by lysing and killing ● are broad-spectrum antimicrobial peptides secreted from
certain cells and bacteria. There are additional chemical the skin and mucous membranes. They are produced in
barriers in the respiratory tract mucosae. much higher quantities when surface barriers are
breached, and inflammation develops.

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body
Fever ● Antihistamine and anti-asthma medications called Mast
● Fever is the elevation of body temperature that reduces cell stabilizers ‒ medications that is used to control
iron in the blood, which inhibits bacterial and fungal allergic disorders that inhibit mast cell degranulation
reproduction. ● Mast cell stabilizers stabilizes cells preventing release of
● Fever also causes increased phagocytosis by histamine ‒ histamine is strongest inflammatory
macrophages. chemical released by mast cell
○ Macrophage eats microorganism ● Mast cell stabilizers:
Pyrogens ○ Cromolyn
● response of the body to foreign materials which causes ○ Nedocromil
the hypothalamus to raise the body temperature. ○ Ketotifen
● Agents that can cause fever or increased temperature. ○ Olopatadine
● Antipyretic/ pyrogens ■ can be used for the eyes to prevent
allergic conjunctivitis
The Spleen and Liver Histamine
● As a result of fever, stores iron and zinc away from the ● a strong inflammatory chemical released by mast cells
rest of the body so they cannot support bacterial growth Macrophages
● are cells that can be able to recognize invaders and
Cells are prepared more quickly because fever increases their trigger chemical response by using surface membrane or
metabolic trait toll-like receptors
● Immune system produces inflammatory chemical once
Active macrophages there is cardinal signs such as:
● release a cytokine that is called endogenous pyrogen or ○ Kinins
interleukin-1, which produces a fever. ○ Prostaglandins
■ can start pain and inflammation
INFLAMMATION (essential for blood and protective
● A tissue response to injury or infection that may include coating in the stomach)
four cardinal signs: ■ NSAIDS such as ibuprofen and
○ Redness naproxen once inhibits prostaglandins
○ Swelling can cause gastric ulceration or "hole
○ Heat in the stomach"
○ Pain ○ Complement system
■ helps dilate localized arterioles and
Eg. Pustules - produces pus cause additional leakage to localized
● Pus - masses of leukocytes, bacterial cells, and damaged capillaries (additional and severe
tissue may form a thick fluid. inflammation)
● Infected cells attract white blood cells, which engulf Local Hyperemia
them. ● occurs when local arterioles dilate, which means that
Impaired function there is congestion in the area with blood.
● is a fifth occurrence that many experts consider to be the Exudates
fifth cardinal sign of inflammation. ● fluid that leaks from the blood into the tissue spaces
● Eg. impaired movement which can cause local swelling or edema
Inflammatory response ● Eg. Pus
● triggered when mast cells release histamine, serotonin,
and heparin. PHAGOCYTOSIS
● The inflammatory response is a tissue-level reaction and ● A process wherein a cell binds to the item or foreign
is therefore related to the tissues and integumentary material it wants to engulf on the cell surface and draws
system. the item inward while engulfing around it larger than 5μm
● The inflammatory response helps to dispose of in diameter.
pathogens and cell debris, triggers the adaptive immune Types of WBC that can trigger phagocytosis:
system to act, and prepares the body to repair damaged 1. Monocytes
tissues. ● influence the development of macrophages that attach to
Diapedesis blood and lymphatic vessels.
● a movement wherein neutrophils squeeze through 2. Neutrophils + eosinophils
capillary walls in response to inflammatory signals. ● These various phagocytic cells make up the
mononuclear phagocytic system to remove foreign
Inflammatory Chemicals particles from the lymph and blood.
Mast cells ● termed as microphages because they are smaller in size,
● first line of defense against antigens entering the body which makes up the mononuclear phagocytic system to
and are present in connective tissues throughout the remove foreign particles from the lymph and blood.

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● Neutrophils are the most abundant and begin to engulf 2 GENERAL CATEGORIES OF BODY DEFENSES
invaders when they find foreign materials in body tissues
3. Macrophages Adaptive (Specific) defense
● Parang c pacman na kumakain ng burger🍔 ● In this type of defense, specialized lymphocytes
● are larger in size, mostly derived from monocytes, and recognize foreign molecules and act against them.
provide most phagocytic activities. ● Both innate and adaptive defense mechanisms work
● Free and fixed macrophages: together to fight infection. Innate defenses act more
○ Free macrophages - search tissue spaces for rapidly than adaptive defenses since they are already
invaders or cellular debris, even though you are present upon birth.
free of disease, these free macrophages search ● Specific defenses depend on the activity of lymphocytes
continue to search for foreign materials and ● The third line of defense
eradicate them. ● Defined as resistance to specific pathogens or their
○ Fixed macrophages - live permanently inside toxins and metabolic byproducts. Adaptive immune
certain organs, such as the liver’s stellate responses are carried out by lymphocytes and
macrophages macrophages that recognize and remember certain
foreign molecules.
All the various phagocytes are collectively called the monocyte ● As a fetus develops, cells learn to recognize proteins and
macrophage system or reticuloendothelial system. large molecules as being “self.”
Additional
NATURAL KILLER CELLS ● The lymphatic system in contrast as it develops
● Prang mga gwardya at pulis responds to “non-self” or foreign antigens.
● Patrol the blood and lymph as part of immunologic
surveillance. They can lyse and kill both cancer and viral ANTIGENS
cells before activation of the adaptive immune system. ● Immunity is triggered by initial exposure to antigens.
● They are part of the cells known as large granular ● Antigens can mobilize adaptive defenses and cause an
leukocytes and have wider actions against pathogens immune response or to produce antibodies.
than the lymphocytes of the adaptive immune system. ● Include proteins, polysaccharides, glycoproteins, and
● They detect generalized abnormalities, such as when glycolipids that are commonly found on cell surfaces.
cell- surface proteins known as major histocompatibility ● Antigens may be natural or synthetic in nature.
complexes (MHC) are lacking.
● They are not phagocytic. COMPLETE ANTIGENS
Cytotoxic T cells
● One that both induces an immune response and reacts
● secrete a poisonous lympho-toxin that kills target cells.
with the products of it
Perforins
○ Adduct: A complex molecule formed by the
● are proteins that diffuse to the target cell.
combination of two or more molecules, such as
● The perforins create holes or pores in the target cell’s
a complete antigen created by a hapten and a
membrane, resulting in lysis of the abnormal cell. NK
carrier.
cells attack cancer cells and those infected with viruses.
○ Hapten: Any small molecule that can elicit an
Tumor-specific antigens
immune response only when attached to a
● a specific antigen used by NK cells to locate and kill
large carrier such as a protein.
cancer cells and this process is called
● Immunogenicity
● Immunological escape- when certain cancer cells can
○ is the ability to stimulate certain lymphocytes
destroy or is either a process of NK cells avoiding their
to multiply.
detection or neutralizing their body defense.
○ Example: pollen, bacteria, viruses and parasites
SPECIES RESISTANCE
● Reactivity
● A final form of innate, nonspecific defense.
○ is the ability to react with activated
● The natural resistance an organism has against
lymphocytes and antibodies that are released
Pathogen.
via immunogenic reactions.
● For example, a human may be resistant to certain
● Once the body has generated antibodies to a
diseases that affect other species of animals. A
hapten-carrier adduct, the small-molecule hapten may
pathogen effective against a dog, for example, may be
also be able to bind to the antibody but will usually not
unable to survive in a human. In reverse, humans can be
initiate an immune response.
infected with measles, gonorrhea, mumps, and syphilis,
none of which affects other animal species.
INCOMPLETE ANTIGENS (HAPTENS)
● Example:
○ Covid-19 which originated in bats is an example ● These are substances unable to induce antibody
of species resistance since bats were not formation on its own but can become immunogenic when
affected when they had this virus but when it linked to proteins (carrier proteins)
was passed to humans it became deadly. ● When haptens and carriers combine, the resulting
molecule is called an adduct, the combination of two or

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1st Year I 2st Semester I Finals
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more molecules. B AND T LYMPHOCYTES RELATED TO ADAPTIVE IMMUNE

● Haptens cannot independently bind to MHC complexes, ● Three important types of cells are needed by the adaptive
so they cannot be presented to T cells. immune system:
● Example: penicillin, dust particles, dander, poison ivy 1. B lymphocytes
(uroshiol), detergents and cosmetics ● control humoral immunity
2. T lymphocytes
ANTIGEN DETERMINANTS ● make up the cellular arm of adaptive immunity; they are
● These are the size and complexity of a molecule non-antibody-producing lymphocytes
determines how it will be able to act as an antigen. 3. Antigen-presenting cells
● Epitopes are part of an antigen that is recognized by the ● perform auxiliary roles instead of responding to specific
immune system, specifically by antibodies and B and T antigens; however, these APCs are needed by T
cells. lymphocytes to recognize their antigens.
● Antibodies or lymphocyte receptors bind to antigenic
determinants similarly to how enzymes bind to
substrates.
● The majority of naturally occurring antigens have various
antigenic determinants located on their surfaces.

SELF ANTIGENS: MHC PROTEINS

● Major Histocompatibility Complex
● In a normal immune system, self-antigens are not foreign
or antigenic to the body, but are extremely antigenic to
other people.
Additional Info:
○ For example in transfusion reactions they are
quick to react or when there are organ
transplants they may be the reason for organ HUMORAL IMMUNE RESPONSE
rejection that is why we have ● The humoral immune response involves B lymphocytes.
immunomodulators. This response is provoked when a B cell encounters its
○ Immunomodulators- drugs that can stimulate antigen.
or suppress our immune system and help the ● In the humoral immune response, antibodies specific for
body fight off certain cancer infections. Some that antigen are manufactured
can prevent organ rejection such as: ● Humoral immunity is also called antibody- mediated
■ Methotrexate immunity. Its name comes from the antibodies that are
■ Cyclosporin present in the body fluids, which used to be referred to as
■ Tacrolimus the body’s “humors” that antigen is manufactured.
● Share the task of presenting peptide fragments on the
cell surface for recognition by T cells ACTIVATION OF B CELLS
● Each of these proteins has a deep groove holding a 1.) B cells activate when encountering an antigen
peptide that is either a self-antigen or a foreign antigen. T 2.) B cells require T cells to activate
lymphocytes only bind antigens presented to them on 3.) T cells that encounter B cells bound to identical foreign
MHC proteins. antigens release cytokines that stimulate the B cells.
○ Class I MHC proteins 4.) The cytokines attract macrophages.
■ are found in the plasma membrane of 5.) Some of the B cell’s clones differentiate into more
every nucleated cell. Their activation memory cells.
eventually results in destruction of 6.) These memory B cells respond quickly to re-exposure to
abnormal cells, which is a significant specific antigens.
component why donated organs are a.) Meaning upon second infection, memory b
often rejected. cells are quick to react and respond.
○ Class II MHC proteins 7.) Other B-cell clones differentiate into antibody- secreting
■ are only found in plasma membranes plasma cells, which can combine with their
of antigen-presenting cells and corresponding foreign antigens and react against them
lymphocytes. It only appears in the Effector cells
plasma mem- brane when the cell is ● secretes antibodies at a rate of approximately 2,000
processing antigens. molecules every second. This activity continues for
between four and five days before each plasma cell dies.
Memory cells
● develop from any clone cells that do not become plasma
cells.

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Institute of Pharmacy S.Y. 2022 - 2023
1st Year I 2st Semester I Finals
Prof. Joshua Kenneth Ng

IMMUNOLOGICAL MEMORY VACCINES

Primary Immune Response ● Edward Jenner
● It is constituted by activation of B cells or T cells after ○ Inventor of the first vaccine, smallpox vaccine.
they first encounter the antigens for which they are ○ experiments with cowpox to stimulate smallpox
specialized to react. immunity are better known than these earlier
● Occurs within 3-6 days attempts at immunization.
● B cells specific for that antigen proliferate into ● As with any challenge to the immune system, the body
approximately 12 generations. must first detect the threat whether it is a pathogenic
● Plasma cells release antibodies into the lymph. The agent or an immunization.
antibodies are transported to the blood and throughout ● There are a variety of vaccine types that are either
the body to help destroy antigen-- bearing agents. This currently in use or in development for the prevention of
continues for several weeks. infectious diseases.
● Most important discovery in human history because
Secondary Immune Response vaccines are capable of eradicating diseases such as
● Occurs when some B cells remain as memory cells polio, measles, mumps, chlorella, and small poxes.
● Produces antibodies when identical antigen is re-
encountered BENEFITS OF VACCINES
● Memory B and T cells ● They do not cause most of the uncomfortable signs and
○ produces secondary immune response symptoms that normally occur during the primary
● After a primary immune response, detectable response.
concentrations of antibodies appear in the blood plasma, ● Their weakened antigens provide immunogenic, reactive
usually five to 10 days after exposure to antigens, and a functional determinants of antigens.
secondary immune response can then occur within one ● Antibody titer
to two days. ○ happens during the primary response, the level
● Secondary immune responses occur faster, with more of antibody activity in the plasma does not peak
effectiveness, than primary immune responses. until one to two weeks after the initial
● The memory cells are “ready for action” because they exposure.
were previously alerted to antigens.
● Provides immunological memory TYPES OF VACCINES
● Memory T cells
○ are produced in the same way as cytotoxic T
Live, Attenuated Vaccines
cells
● As exemplified by the vaccines against measles, mumps,
● Memory helper T cells
rotavirus, smallpox, yellow fever and chickenpox contain
○ are produced along with active helper T cells
laboratory-weakened versions of the original pathogenic
agent.
ACTIVE HUMORAL IMMUNITY ● These vaccines produce strong cellular and antibody
● It is signified by antibodies produced by B cells after responses and typically produce long-term immunity with
encountering antigens. Active humoral immunity is only one to two doses of vaccine.
acquired either naturally or artificially. ● Attenuated
● Natural ○ means the pathogens are extremely weakened
○ acquiring active humoral immunity include but still alive.
development of bacterial or viral infections
● Passive Inactivated Vaccines
○ means of acquiring active humoral immunity
● As exemplified by the inactivated influenza vaccine are
include vaccines
produced by destroying a pathogenic agent with
chemicals, heat, or radiation.
● Your body trains your immune system on how to detect a
certain kind of pathogen.
● This inactivation of the microorganism makes the
vaccine more stable
● These vaccines produce weaker immune responses
therefore additional booster shots are required to
maintain immunity.
○ 2-3 years before you take a booster shot again.
● Listeria, Hepatitis A, flu shots, polio shots, rabies
vaccines

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1st Year I 2st Semester I Finals
Prof. Joshua Kenneth Ng

Subunit Vaccines infection thus stimulating the immune system.

● As exemplified by the recombinant hepatitis B, HPV
vaccine includes only epitopes that most readily Booster Shots
stimulate the immune system. ● Are vaccines that can intensify the immune response
● Because these vaccines only use a few specific antigens, when the same antigen is encountered at a later time.
this reduces the likelihood of adverse reactions ● Diseases that have been eradicated, nearly eradicated, or
● Is a specific antigen that mitigates or reduces adverse extremely weakened by vaccines include smallpox,
drug reactions associated with subunit vaccines. measles, polio, and whooping cough.
● e.g) Novavax
PASSIVE HUMORAL IMMUNITY
● Involves the introduction of antibodies into the body. The
B cells are not challenged by antigens, and
immunological memory does not occur.
● The protection provided by the introduced antibodies
ends when they become naturally degraded.
Natural Passive Immunity
● when antibodies from a mother cross the placenta or are
ingested through her milk the fetus or infants
Artificial Passive Immunity
Toxoid Vaccines ● administration of exogenous antibodies such as gamma
● As exemplified by the diphtheria and tetanus vaccines globulin, such as from the plasma of an immune donor.
are produced by inactivating bacterial toxins with
formalin. ANTIBODIES
● These toxoids stimulate an immune response against the ● can react with antigen or antigen containing particles
bacterial toxins. ● B cells divide and differentiate into plasma cells,
producing antibodies or immunoglobulins (Igs) that react
mRNA Vaccines to destroy antigens or antigen- containing particles.
● mRNA vaccines make proteins in order to trigger an ● Antibodies are produced by lymphocytes and circulate in
immune response. the blood and lymph
● mRNA vaccines have several benefits compared to other ● Antibodies released by plasma cells are involved in
types of vaccines, including shorter manufacturing times humoral immunity, immediate hypersensitivity reactions,
and, because they do not contain a live virus, no risk of and autoimmune disorders.
causing disease in the person getting vaccinated. STRUCTURE OF ANTIBODIES
● mRNA- protein synthesis ● Each antibody has four looped polypeptide chains
connected by sulfur-to-sulfur or disulfide bonds. The
Conjugate Vaccines chains form a molecule known as an antibody monomer.
● As exemplified by the Haemophilus influenzae type B ● The antibody monomer is shaped like a “Y” or a “T”
(Hib) vaccine are a special type of subunit vaccine.
● In a conjugate vaccine, antigens or toxoids from a
microbe are linked to polysaccharides from the outer
coating of that microbe to stimulate immunity (especially
in infants).

Naked DNA Vaccines

● In the experimental stages of development.
● These vaccines would use DNA specific for microbial
antigens to stimulate immunity. This DNA would be
administered by injection (subcutaneous route) and then Heavy chains
body cells would take up the DNA. ● identical to each other and have hinge region that is
● These body cells would then start producing the antigen flexible
and displaying it on their surfaces which would then Light chains
stimulate the immune system. ● are only half as long as each H chain but are also
identical to each other.
Recombinant Vaccines Variable (V) region, Constant (C) region
● Usually seen in insulin. Antigen binding site
● Are experimental vaccines that use either an attenuated ○ found at the V regions of the heavy and light
virus or microbe to introduce microbial DNA into body chains that has a fitting of certain antigenic
cells. determinant.
● These viral vaccines would readily mimic a natural

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1st Year I 2st Semester I Finals
Prof. Joshua Kenneth Ng

Stem of Antibody Monomer Chemotaxis

● determines the class of antibody and formed by 2 C ● phenomenon at which microorganisms efficiently and
regions respond to changes in chemical composition.
C regions
● Constant regions CELLULAR IMMUNE RESPONSE
● are effector regions of antibody that determines the ● Aka cell-mediated immunity
body’s cells and chemicals to which antibody class ● Happens when T cells attach to foreign, antigen- bearing
eliminates antigens. cells such as bacterial cells and interact with direct
cell-to-cell contact.
IMMUNOGLOBULIN Interleukin-1 and Interleukin-2
● IgM, IgA, IgD, IgG and IgE ● stimulate synthesis of cytokines from other T cells.
IgM Colony-stimulating factors
● made up of 5 monomers or Y shaped units that is much ● stimulate leukocyte production in red bone marrow,
larger in plasma activate macrophages, and cause B cells to grow.
IgA CD4 and CD8
● a monomer or dimer that can be found on tears, saliva ● Also known as the cell differentiation.
and breast milk. Most abundant antibody in body ● glycoprotein surface receptors that are different from T
secretions cell antigen receptors and help with interactions between
IgD, IgG and IgE other cells and T cells.
● monomers with similar Y- shaped structures
ACTIVATION OF CD4 AND CD8 CELLS
● Effector cells
○ involved in cellular immunity
● CD4 cells usually become helperT cells, and activate B
cells, other T cells, and macrophages. They direct the
adaptive immune response.
● CD8 cells become cytotoxic T cells, destroying cells in
the body that contain anything foreign.
● Some CD4 cells become regulatory T cells, which
regulate the immune response.
● Activated CD4 and CD8 cells can also become memory T
cells.
● All T cells have a CD3 receptor complex in the plasma
membranes that eventually activates them to recognize
antigens.

ANTIBODY TARGETS AND FUNCTIONS

● Antibodies commonly attack antigens directly, activate
complement or stimulate inflammation.
Agglutination
● clumping of particles together capable of triggering MAJOR EFFECTOR CELLS
adaptive immune response Helper T cells
Precipitation ● Are central to adaptive immunity. They mobilize both its
● forming insoluble complexes. humoral and cellular components.
Complement activation ● When activated by APC activity, TH cells help to activate
● generally more important in protecting against infection both B and T cells. They also “encourage” B and T cells
than direct antibody attack to proliferate
Opsonization ● Without the aid of these “director” TH cells, there will be
● uses opsonins that attracts macrophages and absolutely no adaptive immune response
neutrophils to tag pathogens for elimination via ● Their cytokines provide chemical assistance require to
phagocytosis. recruit other immune cells.

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1st Year I 2st Semester I Finals
Prof. Joshua Kenneth Ng

Helper T Cells:
TH1 cells:
● These cells control most components of cellular
immunity. They stimulate inflammation, cause activation
of macrophages, and encourage differentiation of
cytotoxic T cells.
TH2 cells:
● They mostly defend against parasitic worms and also
promote allergies. They mobilize the eosinophils and
cause activation of immune responses depending on B
cells and formation of antibodies.
TH17 cells:
● They release IL-17,which helps link adaptive and innate
immunity. This substance promotes inflammatory
responses that oppose extracellular microbes; these may
be the cause of most autoimmune diseases.

Cytotoxic T cells
● Are also called activated CD8 cells. They are abbreviated
as TC cells, and are the only T cells that directly attack
and kill other types of cells.
● The body is patrolled by TC cells, which circulate through
the blood and lymph, as well as through the lymphoid
organs.
● They search for cells with recognizable antigens. They
primarily target cells infected with viruses, but also
attack tissue cells infected with specific intracellular
parasites or bacteria, cancer cells, and foreign cells that
may have been introduced via organ transplants or blood
transfusions.
AN IMMUNIZING PHARMACIST
Regulatory T cells WHY DO WE IMMUNIZE?
● TReg cells are related to TH cells. ● ”Vaccines are the most important invention in human
● They reduce the immune response by either direct history. Eradicating public health crisis and revolutionized
contact, or by the release of inhibitory cytokines. These global health”
cells are important to prevent auto-immune reactions.
They suppress self- reactive lymphocytes in peripheral ROLES OF AN IMMUNIZING PHARMACIST
tissues. ● Role in immunization service delivery in the pharmacy,
● It is hoped that they may be used in the future to cause including patient care – from assessment of vaccination
tolerance to transplanted tissues, and to reduce severity needs, patient screening, vaccine administration,
of auto-immune diseases. counseling post vaccination, until monitoring,
management and reporting of AEFI
IMBALANCE OF IMMUNE SYSTEM HOMEOSTASIS ● “Section 5, Article I of RA No. 10918 defines adult
Autoimmune conditions vaccines as cervical cancer, flu (influenza),
● Happens when the body then produces auto antibodies pneumococcal, other pre-exposure prophylactic vaccines
and cytotoxic T cells that destroy the “self” tissues. to be administered to patients aged eighteen (18) years
● When the immune system can no longer distinguish and above, and such other vaccines as may be defined by
between “self” and “foreign” antigens. the Department of Health (DOH) in an administrative
● Autoimmune diseases are treated with agents such as issuance”
corticosteroids, which suppress the entire immune Vaccine Preparation:
system. Today, treatments aim at only specific immune ● Syringe/Needle Selection
responses. There are many possible “targets” for these ● Inspecting Vaccine
treatments because of the immune system’s complexity. ● Reconstitution
● Filling Syringes
Routes, Site and Needle Size Based upon:
● Age
● Volume of material
● Viscosity of material
● Size of muscle
● Recommended depth

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1st Year I 2st Semester I Finals
Prof. Joshua Kenneth Ng

ADMINISTERING VACCINES ● Live, attenuated influenza (LAIV [FluMist]) vaccine is the

only vaccine administered by the intranasal route.
SUBCUTANEOUS (SC) INJECTIONS ● Done in a seated upright position with head tilted back
● Do not repeat if patient cough, sneezes or expels dose.

ORAL (PO) ROUTE

● Oral vaccine is administered through drops to the mouth.
● Rotavirus vaccine (RV1 [Rotarix], RV5 [RotaTeq]) is the
only routinely recommended vaccine administered orally.
● Carefully and slowly administer to prevent gag reflex
● Administer prior to injections

● Directly injected in our subcutaneous tissue at a 45

degree angle by pinching the acromion to prevent the
vaccine from flowing into the muscle which may cause
pain.
INTRAMUSCULAR (IM) INJECTIONS

NEEDLE GAUGE AND LENGTH

INTRADERMAL (ID) INJECTIONS

● Injected in the dermis layer and must form a “wheal”

upon injection.
INTRANASAL (IN) INJECTIONS
● Intranasal vaccine is administered into each nostril using
a manufacturer-filled nasal sprayer.

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