Kidney Anatomy and
    Physiology

        An Overview

         Noah Hoffman
            2006
Functions of the Kidney:
    Maintaining balance
• Regulation of body fluid volume and
  osmolality
• Regulation of electrolyte balance
• Regulation of acid-base balance
• Excretion of waste products (urea, ammonia,
  drugs, toxins)
• Production and secretion of hormones
• Regulation of blood pressure
The Kidney and the Nephron
                             A.   Renal Vein
                             B.   Renal Artery
                             C.   Ureter
                             D.   Medulla
                             E.   Renal Pelvis
                             F.   Cortex
                             7.   Ascending loop of
                                  Henle
                             8.   Descending loop of
                                  Henle
                             9.   Peritubular capillaries
                             10. Proximal tubule
                             11. Glomerulus
                             12. Distal tubule
The Nephron
• Functional unit of the kidney
  (1,000,000)
• Responsible for urine formation:
  – Filtration
  – Secretion
  – Reabsorption
Components of
  the nephron

•Glomerulus
•Afferent and
Efferent arterioles
•Proximal Tubule
•Loop of Henle
•Distal Tubule
•Collecting Duct
Overview of nephron function




From http://www.emc.maricopa.edu/faculty/farabee/BIOBK/BioBookEXCRET.html
Filtration
THE GLOMERULUS
Plasma is filtered through the
            glomerular barrier
•Components of plasma cross the three layers of the
glomerular barrier during filtration
   •Capillary endothelium
   •Basement membrane (net negative charge)
   •Epithelium of Bowman’s Capsule (Podocytes –filtration
   slits allow size <60kD)
•The ability of a molecule to cross the membrane depends on
size, charge, and shape
• Glomerular filtrate therefore contains all molecules not
contained by the glomerular barrier - it is NOT URINE YET!
Glomerular Filtration Rate
            (GFR)
• Measure of functional capacity of the
  kidney
• Dependent on difference in pressures
  between capillaries and Bowman’s
  space
• Normal = 120 ml/min =7.2 L/h=180
  L/day!! (99% of fluid filtered is reabs.)
Oncotic pressure
      Oncotic pressure is the
      component of total osmotic
      pressure due to colloid
      particles.


      Water molecules cross the
      membrane to equalize the
      concentration of colloid
      particles on each side.
Glomerular filtration rate (GFR)
• Depends on the difference in hydrostatic and oncotic
  pressure on either side of the glomerular basement
  membrane                                   GFR
                                             =
 Glomerular       Bowman’s
 Capillary (GC)   space (BS)        Kf(PGC - PBS - COPGC)
                                       P = hydrostatic
         PGC         PBS                  pressure

     COPGC          COPBS           COP = colloid osmotic
                                         pressure
                                      Kf determined by
                                      surface area and
                                     permeability of H2O
Reabsorption
and secretion
Reabsorption
• Active Transport –requires ATP
  – Na+, K+ ATP pumps
• Passive Transport-
  – Na+ symporters (glucose, a.a., etc)
  – Na+ antiporters (H+)
  – Ion channels
  – Osmosis
Factors influencing
            Reabsorption
• Saturation: Transporters can get saturated
  by high concentrations of a substance -
  failure to resorb all of it results in its loss in
  the urine (eg, renal threshold for glucose is
  about 180mg/dl).
• Rate of flow of the filtrate: affects the time
  available for the transporters to reabsorb
  molecules.
What is Reabsorbed Where?
Proximal tubule - reabsorbs 65 % of filtered Na+ as well
as Cl-, Ca2+, PO4, HCO3-. 75-90% of H20. Glucose,
carbohydrates, amino acids, and small proteins are
also reabsorbed here.
Loop of Henle - reabsorbs 25% of filtered Na+.
Distal tubule - reabsorbs 8% of filtered Na+. Reabsorbs
HCO3-.
Collecting duct - reabsorbs the remaining 2% of Na+
only if the hormone aldosterone is present. H20
depending on hormone ADH.
Secretion
• Proximal tubule – uric acid, bile salts,
  metabolites, some drugs, some
  creatinine
• Distal tubule – Most active secretion
  takes place here including organic
  acids, K+, H+, drugs, Tamm-Horsfall
  protein (main component of hyaline
  casts).
Countercurrent exchange
• The structure and transport
  properties of the loop of
  Henle in the nephron create
  the Countercurrent
  multiplier effect.
• A substance to be exchanged
  moves across a permeable
  barrier in the direction from
  greater to lesser
  concentration.

  Image from http://en.wikipedia.org/wiki/Countercurrent_exchange
Countercurrent exchange

• Countercurrnet exchange is
  found throughout nature…
• Birds reduce heat loss
  through their feet by heating
  venous (returning) blood and
  cooling arterial (outgoing)
  blood in their legs.



      Image from http://ecology.botany.ufl.edu/ecologyf02/homeostasis.html
Loop of Henle
 – Goal= make isotonic filtrate
   into hypertonic urine (don’t
   waste H20!!)
 – Counter-current multiplier:
    • Descending loop is permeable
      to Na+, Cl-, H20
    • Ascending loop is impermeable
      to H20- active NaCl transport
    • Creates concentration gradient
      in interstitium
    • Urine actually leaves hypotonic
      but CD takes adv in making
      hypertonic
Hormones Produced by the
          Kidney
• Renin:
  – Released from juxtaglomerular apparatus when low blood
    flow or low Na+. Renin leads to production of angiotensin II,
    which in turn ultimately leads to retention of salt and water.
• Erythropoietin:
  – Stimulates red blood cell development in bone marrow. Will
    increase when blood oxygen low and anemia (low
    hemoglobin).
• Vitamin D3:
  – Enzyme converts Vit D to active form 1,25(OH)2VitD.
    Involved in calcium homeostasis.
Renin, Angiotensin, Aldosterone:
Regulation of Salt/Water Balance
Renin/AII and Regulation of GFR
                       GFR = Kf(PGC - PBS - COPGC)

• “flight or fright”
∀⇑ sympathetic tone
• afferent arteriolar constriction (divert cardiac output to other
organs)
∀⇓PGC
∀⇓GFR and renal blood flow
Renin/AII and Regulation of GFR
                  GFR = Kf(PGC - PBS - COPGC)
•Low BP sensed in afferent
arteriole or low Na in distal tubule
•renin released
•renin converts angiotensinogen
to Angiotensin I
                                          PGC⇑
•ACE converts AI to AII
•efferent > afferent arteriolar
constriction
∀⇑ PGC ⇒ ⇑ GFR (this is                  constricts
AUTOREGULATION of GFR)
Aldosterone
• Secreted by the adrenal glands in
  response to angiotensin II or high
  potassium
• Acts in distal nephron to increase
  resorption of Na+ and Cl- and the
  secretion of K+ and H+
• NaCl resorption causes passive
  retention of H2O
Anti-Diuretic Hormone (ADH)
• Osmoreceptors in the brain (hypothalamus)
  sense Na+ concentration of blood.
• High Na+ (blood is highly concentrated)
  stimulates posterior pituitary to secrete ADH.
• ADH upregulates water channels on the
  collecting ducts of the nephrons in the kidneys.
• This leads to increased water resorption and
  decrease in Na concentration by dilution
Case I
• A 52 yo male is seen for a routine physical
  exam for the first time in a few years. His
  physician discovers that the patient has been
  feeling more tired than usual for “a while.” He
  also complains of increased thirst and
  hunger, and says that he has to get up
  several times at night to urinate.
• The lab measured a random blood glucose of
  350 mg/dl, urine dipstick positive for glucose,
  and urine albumin/creatinine of 40 mg/g.
Case 1 - DMII
• Diabetes mellitus type II (“adult onset”)
• Diabetes from Greek words meaning
  "siphon" or "run through”; mellitus is Latin for
  “sweet.”
• Saturation of glucose transporters results in
  glucose in urine.
• Glucose in urine results in osmotic diuresis.
• Chronic hyperglycemia leads to
  microvascular damage, including damage to
  glomerular capillary wall, resulting in
  microalbuminuria.
Case 2
• A 39-yr-old male with AIDS was admitted with
  nausea, vomiting, abdominal pain, light-
  headedness on standing, and weight loss.
  During hospitalization, the patient developed
  hypotonic polyuria with urine volumes of
  9L/day associated with intense thirst.
• serum Na - 149 mmol/L [136-145]
• urine osmolality - 71 to 88 mmol/kg
  [100-1000]
Case 2
• A water restriction test was performed, in which the
  patient was given about 450 ml of 3% saline IV over
  2 hours.
   – serum osm - 306 mmol/kg [280-300]
   – urine osm - 102
   – urinary ADH - undetectable
• MR imaging showed changes in the posterior
  pituitary.
• In response to treatment with desmopressin (10 g
  twice daily by nasal spray), urine volumes decreased
  to 2–3 liters per day. The patient later died of bowel
  perforation. Autopsy showed evidence of damage to
  the posterior pituitary caused by CMV infection.
Case 2 - Diabetes
       Insipidus
•   Inability to concentrate urine
    despite high serum sodium and
    osmolality. Results in large
    volume of dilute urine.
•   Central
    – damage to the posterior pituitary
      results in inadequate ADH
      production
    – treatment is exogenous ADH
•   Nephrogenic
    – kidney unresponsive to ADH
    – can be hereditary or acquired
      (eg, lithium therapy)
    – serum ADH is high
Case 3
• A 61 year old male presented with confusion
  and seizures two days after starting a new
  medication (citalopram, an antidepressant).
  –   serum Na - 124 mmol/L [136–145]
  –   serum osmolarity - 263 mOsm/L [285–295]
  –   urine Na - 141 mEq/L [40-220]
  –   urine osmolarity - 400 mosm/L [100-1000]
  –   urine output - < 1L/day
• The patient's serum sodium gradually
  normalized after the medication was
  discontinued.
Case 3 - SIADH
• SIADH = syndrome of inappropriate
  antidiuretic hormone secretion
• Open channels in the collecting duct lead to
  excessive water resorption and a dilutional
  hyponatremia.
• can be caused by brain injury, ectopic
  production by tumors, various drugs, major
  surgery, pulmonary diseases, exogenous
  ADH
• Treatment includes water restriction and salt
  administration

Nh lm322 renal_2006

  • 1.
    Kidney Anatomy and Physiology An Overview Noah Hoffman 2006
  • 2.
    Functions of theKidney: Maintaining balance • Regulation of body fluid volume and osmolality • Regulation of electrolyte balance • Regulation of acid-base balance • Excretion of waste products (urea, ammonia, drugs, toxins) • Production and secretion of hormones • Regulation of blood pressure
  • 4.
    The Kidney andthe Nephron A. Renal Vein B. Renal Artery C. Ureter D. Medulla E. Renal Pelvis F. Cortex 7. Ascending loop of Henle 8. Descending loop of Henle 9. Peritubular capillaries 10. Proximal tubule 11. Glomerulus 12. Distal tubule
  • 5.
    The Nephron • Functionalunit of the kidney (1,000,000) • Responsible for urine formation: – Filtration – Secretion – Reabsorption
  • 6.
    Components of the nephron •Glomerulus •Afferent and Efferent arterioles •Proximal Tubule •Loop of Henle •Distal Tubule •Collecting Duct
  • 7.
    Overview of nephronfunction From http://www.emc.maricopa.edu/faculty/farabee/BIOBK/BioBookEXCRET.html
  • 8.
  • 9.
  • 10.
    Plasma is filteredthrough the glomerular barrier •Components of plasma cross the three layers of the glomerular barrier during filtration •Capillary endothelium •Basement membrane (net negative charge) •Epithelium of Bowman’s Capsule (Podocytes –filtration slits allow size <60kD) •The ability of a molecule to cross the membrane depends on size, charge, and shape • Glomerular filtrate therefore contains all molecules not contained by the glomerular barrier - it is NOT URINE YET!
  • 11.
    Glomerular Filtration Rate (GFR) • Measure of functional capacity of the kidney • Dependent on difference in pressures between capillaries and Bowman’s space • Normal = 120 ml/min =7.2 L/h=180 L/day!! (99% of fluid filtered is reabs.)
  • 12.
    Oncotic pressure Oncotic pressure is the component of total osmotic pressure due to colloid particles. Water molecules cross the membrane to equalize the concentration of colloid particles on each side.
  • 13.
    Glomerular filtration rate(GFR) • Depends on the difference in hydrostatic and oncotic pressure on either side of the glomerular basement membrane GFR = Glomerular Bowman’s Capillary (GC) space (BS) Kf(PGC - PBS - COPGC) P = hydrostatic PGC PBS pressure COPGC COPBS COP = colloid osmotic pressure Kf determined by surface area and permeability of H2O
  • 14.
  • 15.
    Reabsorption • Active Transport–requires ATP – Na+, K+ ATP pumps • Passive Transport- – Na+ symporters (glucose, a.a., etc) – Na+ antiporters (H+) – Ion channels – Osmosis
  • 16.
    Factors influencing Reabsorption • Saturation: Transporters can get saturated by high concentrations of a substance - failure to resorb all of it results in its loss in the urine (eg, renal threshold for glucose is about 180mg/dl). • Rate of flow of the filtrate: affects the time available for the transporters to reabsorb molecules.
  • 17.
    What is ReabsorbedWhere? Proximal tubule - reabsorbs 65 % of filtered Na+ as well as Cl-, Ca2+, PO4, HCO3-. 75-90% of H20. Glucose, carbohydrates, amino acids, and small proteins are also reabsorbed here. Loop of Henle - reabsorbs 25% of filtered Na+. Distal tubule - reabsorbs 8% of filtered Na+. Reabsorbs HCO3-. Collecting duct - reabsorbs the remaining 2% of Na+ only if the hormone aldosterone is present. H20 depending on hormone ADH.
  • 19.
    Secretion • Proximal tubule– uric acid, bile salts, metabolites, some drugs, some creatinine • Distal tubule – Most active secretion takes place here including organic acids, K+, H+, drugs, Tamm-Horsfall protein (main component of hyaline casts).
  • 20.
    Countercurrent exchange • Thestructure and transport properties of the loop of Henle in the nephron create the Countercurrent multiplier effect. • A substance to be exchanged moves across a permeable barrier in the direction from greater to lesser concentration. Image from http://en.wikipedia.org/wiki/Countercurrent_exchange
  • 21.
    Countercurrent exchange • Countercurrnetexchange is found throughout nature… • Birds reduce heat loss through their feet by heating venous (returning) blood and cooling arterial (outgoing) blood in their legs. Image from http://ecology.botany.ufl.edu/ecologyf02/homeostasis.html
  • 22.
    Loop of Henle – Goal= make isotonic filtrate into hypertonic urine (don’t waste H20!!) – Counter-current multiplier: • Descending loop is permeable to Na+, Cl-, H20 • Ascending loop is impermeable to H20- active NaCl transport • Creates concentration gradient in interstitium • Urine actually leaves hypotonic but CD takes adv in making hypertonic
  • 23.
    Hormones Produced bythe Kidney • Renin: – Released from juxtaglomerular apparatus when low blood flow or low Na+. Renin leads to production of angiotensin II, which in turn ultimately leads to retention of salt and water. • Erythropoietin: – Stimulates red blood cell development in bone marrow. Will increase when blood oxygen low and anemia (low hemoglobin). • Vitamin D3: – Enzyme converts Vit D to active form 1,25(OH)2VitD. Involved in calcium homeostasis.
  • 24.
  • 25.
    Renin/AII and Regulationof GFR GFR = Kf(PGC - PBS - COPGC) • “flight or fright” ∀⇑ sympathetic tone • afferent arteriolar constriction (divert cardiac output to other organs) ∀⇓PGC ∀⇓GFR and renal blood flow
  • 26.
    Renin/AII and Regulationof GFR GFR = Kf(PGC - PBS - COPGC) •Low BP sensed in afferent arteriole or low Na in distal tubule •renin released •renin converts angiotensinogen to Angiotensin I PGC⇑ •ACE converts AI to AII •efferent > afferent arteriolar constriction ∀⇑ PGC ⇒ ⇑ GFR (this is constricts AUTOREGULATION of GFR)
  • 27.
    Aldosterone • Secreted bythe adrenal glands in response to angiotensin II or high potassium • Acts in distal nephron to increase resorption of Na+ and Cl- and the secretion of K+ and H+ • NaCl resorption causes passive retention of H2O
  • 28.
    Anti-Diuretic Hormone (ADH) •Osmoreceptors in the brain (hypothalamus) sense Na+ concentration of blood. • High Na+ (blood is highly concentrated) stimulates posterior pituitary to secrete ADH. • ADH upregulates water channels on the collecting ducts of the nephrons in the kidneys. • This leads to increased water resorption and decrease in Na concentration by dilution
  • 29.
    Case I • A52 yo male is seen for a routine physical exam for the first time in a few years. His physician discovers that the patient has been feeling more tired than usual for “a while.” He also complains of increased thirst and hunger, and says that he has to get up several times at night to urinate. • The lab measured a random blood glucose of 350 mg/dl, urine dipstick positive for glucose, and urine albumin/creatinine of 40 mg/g.
  • 30.
    Case 1 -DMII • Diabetes mellitus type II (“adult onset”) • Diabetes from Greek words meaning "siphon" or "run through”; mellitus is Latin for “sweet.” • Saturation of glucose transporters results in glucose in urine. • Glucose in urine results in osmotic diuresis. • Chronic hyperglycemia leads to microvascular damage, including damage to glomerular capillary wall, resulting in microalbuminuria.
  • 31.
    Case 2 • A39-yr-old male with AIDS was admitted with nausea, vomiting, abdominal pain, light- headedness on standing, and weight loss. During hospitalization, the patient developed hypotonic polyuria with urine volumes of 9L/day associated with intense thirst. • serum Na - 149 mmol/L [136-145] • urine osmolality - 71 to 88 mmol/kg [100-1000]
  • 32.
    Case 2 • Awater restriction test was performed, in which the patient was given about 450 ml of 3% saline IV over 2 hours. – serum osm - 306 mmol/kg [280-300] – urine osm - 102 – urinary ADH - undetectable • MR imaging showed changes in the posterior pituitary. • In response to treatment with desmopressin (10 g twice daily by nasal spray), urine volumes decreased to 2–3 liters per day. The patient later died of bowel perforation. Autopsy showed evidence of damage to the posterior pituitary caused by CMV infection.
  • 33.
    Case 2 -Diabetes Insipidus • Inability to concentrate urine despite high serum sodium and osmolality. Results in large volume of dilute urine. • Central – damage to the posterior pituitary results in inadequate ADH production – treatment is exogenous ADH • Nephrogenic – kidney unresponsive to ADH – can be hereditary or acquired (eg, lithium therapy) – serum ADH is high
  • 34.
    Case 3 • A61 year old male presented with confusion and seizures two days after starting a new medication (citalopram, an antidepressant). – serum Na - 124 mmol/L [136–145] – serum osmolarity - 263 mOsm/L [285–295] – urine Na - 141 mEq/L [40-220] – urine osmolarity - 400 mosm/L [100-1000] – urine output - < 1L/day • The patient's serum sodium gradually normalized after the medication was discontinued.
  • 35.
    Case 3 -SIADH • SIADH = syndrome of inappropriate antidiuretic hormone secretion • Open channels in the collecting duct lead to excessive water resorption and a dilutional hyponatremia. • can be caused by brain injury, ectopic production by tumors, various drugs, major surgery, pulmonary diseases, exogenous ADH • Treatment includes water restriction and salt administration