Physiology د. نصير جواد المختار

Lecture III: Glomerular Filtration Rate, Basic Mechanism of Absorption and Secretion in Tubules

Glomerular Filtration Rate (GFR):

It is the fluid that filtrate through the glomerulus into Bowman’s capsule each minute. It is about 125 ml/min. or 180 L/day in male (10% lower in female). The high GFR is due to very high permeability of capillaries of glomerulus. Because the inner side of the pores of glomerular membrane is negatively charged repelling other negatively charged molecules that tend to pass through pores. The glomerular membrane is completely impermeable for all plasma proteins but it is highly permeable to all other dissolved substances of normal plasma. The composition of the glumerular filtrate is the same as plasma except that it has no significant amount of proteins. The filtration fraction in normal plasma flow through both kidneys is 1/5 or 20% (125 ml/min.) it determined by:

  1. The balance of hydrostatic and colloid osmotic forces acting across the capillary membrane.
  2. Capillary filtration coefficient (Kf).

The glomerular capillaries have much higher rate filtration than other capillaries because of high glomerular hydrostatic pressure and large (Kf).

Glomerular capillary has 3 layers: endothelium, basement membrane and epithelial cells. The layers make up the filtration barrier. Epithelium of capillary is performed by thousands of smallpores (fenestrate) similar to fenestrated capillaries found in the liver.

Factors that favoring filtration:

  1. Glomeular hydrostatic pressure (60).
  2. Bowman’s capsule colloid osmotic pressure (0).

Factors that opposing filtration:

  1. Glomerular colloid osmotic pressure (18).
  2. Bowman’s capsule hydrostatic pressure (32).

Physiological control of GF and renal blood flow:

  1. Sympathetic nervous system: All the blood vessels of kidneys are richly innervations by sympathetic nerve fibers. Strong activation of renal sympathetic nervous system constricts the renal arterioles and decrease BF and GFR. Reflex mechanism action of the sympathetic nervous system has low important because it adapt within minutes or hours. The reflex mechanism role in long term control of renal bold flow GFR. Renal sympathetic nerves are important in reducing GFR during sever, acute disturbance such as sever hemorrhage and brain ischemia. In normal resting person, there appear to be little sympathetic tone to the kidney.
  2. Hormonal and autacoids control of renal circulation: Norepinephrine, epinephrine and endothelin constrict blood vessels and decrease GFR. Blood level of these hormones is parallel the activity of sympathetic nervous system, especially under extreme conditions such as sever hemorrhage. Endothelin level increased in certain diseases such as toxemia of pregnancy, acute renal failure and chronic uremia, cause renal vasoconstriction and decrease GFR. Angitensin II constricts efferent arterioles. Increased angitensin II occurs with low sodium diet or volume depletion. Endothelial derived nitric oxide decrease renal vascular resistance and increase GFR. Prostaglandin and bradykinin tend to increase GFR.

Basic Mechanism of Absorption and Secretion in Tubules:

  1. Proximal tubule: Normally about 65% of filtered Na, water and lower percentage of Cl are reabsorbed here. Na ions are reabsorbed by passive diffusion, facilitated diffusion or by co-transport with glucose, amino acids and by counter-transport in an exchange with H ions. All depending primarily on the electrochemical gradient of Na ions created by active Na-K ATPase pump. Cl ions are reabsorbed by passive and co-transport mechanisms. Water is reabsorbed by osmosis. Proteins are reabsorbed through the brush border of the proximal tubule by process of pinocytosis. The amount of Na in the tubular fluid decreases markedly along the proximal tubule. The concentration of Na and the total osmolarity remains relatively constant (isotonic) because water permeability of the proximal tubules are so great that water reabsorption proportional to Na reabsorption. The proximal tubules are also the site for secretion of organic acids and bases (bile salts, oxalate, urate, catecholamines), drugs toxins and PAH (Fig.5).
  2. Loop of Henle:About 20% of flirted water is reabsorbed in the descending limb loop of Henle. Ascending thin limb and thick segment is impermeable to water. About 25% of filtered Na, Cl and K (other ions such as Ca, HCO3, Mg) are absorbed in the loop of Henle mainly in the thick ascending limb. NA ions are reabsorbed secondary active to Na-K-2Cl co-transport and by Na-H secondary active counter-transport mechanisms. Because the thick ascending loop of Henle is impermeable to water, most of the water remain in tubule, tubular fluid becomes very dilutes as it flow toward the distal tubule (hypotonic).
  3. Distal tubule: Early part of the distal tubule has characteristic of thick segment of ascending limb of loop of Henli. It reabsorbs most of ions including Na, K, Cl and impermeable to water and urea. The second half of the distal and cortical collecting tubule reabsorb Na ion in an exchange with K ions (Na-K ATPase pump) under effect of aldosterone hormone. Secretion of H ions by H-ATPase pump, after being generated inside the cell by action of carbonic anhydrase on water and CO2 to form carbonic acid which then dissociates into H ions and HCO3 ions are reabsorbed across the basolateral membrane. Permeability of the late distal tubule and cortical collecting duct to water is controlled by ADH (vasopressin). These segments are permeable to water in presence of ADH and impermeable to water in absence of the hormone.
  4. Medullary collecting duct: Reassure less than 10% of the filtered water and Na. it plays an important role in determining the final urine output of water and solutes. Permeability to water is under the control of ADH.Permeable to urea. It is capable of secreting H ions against concentration gradient.

Factors affect the rate of reabsorption fluid:

These factors play role in determining the rate of fluid volume excretion (urine):

  1. Osmotic dieresis: In diabetes mellitus in which the proximal tubules fail to reabsorb all the glucose, non absorbed glucose passes through the tubules and carries a large of water and other substances that filtered in excessive quantities from the plasma such as sucrose, manitol and urea.
  2. Plasma colloid osmotic pressure: A sudden increase in plasma colloid osmotic pressure decrease rate of fluid excretion due to decrease GFR and increase tubular reabsorption.
  3. Sympathetic stimulation: It causes constriction of the afferent arterioles, decrease the glomerular pressure and decrease GFR, the blood flow into peritubular capillaries is decreased increasing tubular reabsorption.
  4. Arterial pressure: When renal autoregulatory mechanism is intact, a change in blood pressure causes a change in dieresis and natriuresis. Small increase in arterial pressure causes increase in urinary excretion of Na and water. This result from two effects:
  1. Increase in arterial pressure, increase glomerular pressure, which in turn increase GFR leading to increased urine output.
  2. Increases in arterial pressure also increase the peritubular capillary, decreasing tubular reabsorption.
  1. Hormonal control:
  1. ADH: Increase permeability of distal tubule, collecting tubule and collecting duct to water, decrease urinary volume output.
  2. Aldosterone: Is secreted from adrenal cortex, increase reabsorption of Na ions and increase K ions secretion in cortical collecting tubule.
  3. Angiotensin II: Stimulate aldosterone secretion which in turn increase Na and water reabsorption, constricts the efferent arterioles and increase Na and tubule to increase Na and water reabsorption. It effect directly on proximal tubules to increase Na and water reabsorption by stimulating Na-K ATPase pump at the basolateral membrane of tubular cell and Na-H exchange at luminal side the tubular cell.
  4. Atrial natruretic peptide:This is released from cardiac atria as a result of plasma volume expansion. It inhibits the reabsorption of Na and water by renal tubules especially in collecting ducts with increase urinary output.
  5. Parathyroid hormone: Increase the reabsorption of CA and Mg ions from ascending limb of loop of Henli and distal tubule. It inhibits reabsorption of phosphate from the proximal tubule.

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