Physiology of Kidneys (Renal System)

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Physiology of Kidneys(Renal System)

• Dr. Sherwan Rahman Sulaiman
• MD, MSc, PhD
• www.doctorsherwan.com

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Functions of the KidneyMaintaining balance

1. Regulation of body fluid volume and osmolality
2. Regulation of electrolyte balance
3. Regulation of acid-base balance
4. Excretion of waste products (urea, ammonia,
   drugs, toxins)
5. Production and secretion of hormones
6. Regulation of blood pressure

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The Kidney and the Nephron

• Renal Vein
• Renal Artery
• Ureter
• Medulla
• Renal Pelvis
• Cortex
• Ascending loop of Henle
• Descending loop of Henle
• Peritubular capillaries
• Proximal tubule
• Glomerulus
• Distal tubule

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The Nephron

• Functional unit of the kidney (1,000,000)
• Responsible for urine formation
• Filtration
• Secretion
• Reabsorption

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Components of the nephron

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

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Overview of nephron function
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Filtration
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THE GLOMERULUS
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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 Bowmans Capsule (Podocytes
  filtration slits allow size lt60kD)
• 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!

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Glomerular Filtration Rate (GFR)

• Measure of functional capacity of the kidney
• Dependent on difference in pressures between
  capillaries and Bowmans space
• Normal 120 ml/min 7.2 L/h180 L/day!! (99 of
  fluid filtered is reabs.)

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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.
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Glomerular filtration rate (GFR)

• Depends on the difference in hydrostatic and
  oncotic pressure on either side of the glomerular
  basement membrane

GFR Kf(PGC - PBS - COPGC) P hydrostatic
pressure COP colloid osmotic pressure Kf
determined by surface area and permeability of
H2O
Glomerular Capillary (GC)
Bowmans space (BS)
PGC
PBS
COPGC
COPBS
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Reabsorption

• Active Transport requires ATP
• Na, K ATP pumps
• Passive Transport-
• Na symporters (glucose, a.a., etc)
• Na antiporters (H)
• Ion channels
• Osmosis

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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.

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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.
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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).

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Loop of Henle

• Goal make isotonic filtrate into hypertonic
  urine (dont 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

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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.

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Renin, Angiotensin, Aldosterone Regulation of
Salt/Water Balance
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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

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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
• ACE converts AI to AII
• efferent gt afferent arteriolar constriction
• ? PGC ? ? GFR (this is AUTOREGULATION of GFR)

PGC?
constricts
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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

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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