BLOCK: URIN 313 PHYSIOLOGY OF THE URINARY SYSTEM LECTURE 3 1 Dr. Amel Eassawi

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BLOCK: URIN 313PHYSIOLOGY OF THE URINARY SYSTEM LECTURE 3

Dr. Amel Eassawi

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TUBULAR REABSORPTION - 1

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OBJECTIVESQualitatively describe the forces that determine movement of reabsorbed fluid

from interstitium into peritubular capillaries. Understand pressure natriuresis, pressure diuresis and osmotic diuresis.State the major characteristics of the proximal-tubular systems for active

reabsorption of organic nutrients.List the approximate percentages of the filtered load of sodium reabsorbed by

the various tubular segments.Understand the active step of sodium reabsorption in all sodium-reabsorbing

segments.Understand the mechanisms of water reabsorption.Understand the water permeability characteristics of each tubular segment.Understand the maximum urinary osmolarity.Define obligatory water loss, and understand its determinants.

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TUBULAR REABSORPTION All plasma constituents are filtered in the glomeruli except plasma

protein. After filtration, essential material and electrolytes needed are

reabsorbed but waste products are eliminated. Tubular reabsorption is highly selective process. GFR is 125ml/min, out of this 124ml/min is reabsorbed. 1ml/min

excreted.• 99% of water is reabsorbed.• 99.5% Na+ is reabsorbed.• 100% glucose is reabsorbed.

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TUBULAR REABSORPTION

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TUBULAR REABSORPTION There is passive and active reabsorption of different

substances. Passive Reabsorption occurs from tubular lumen to the

plasma (trans epithelial transport), when no energy is spent. Movement occurs due to electro-chemical or osmotic gradient.

Active Reabsorption is, when energy is required for trans epithelial transport i.e. when there is movement of substance from tubular lumen to plasma against electro chemical gradient. e.g. Na+ , Glucose, Amino acid, Phosphate (PO4

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STEPS OF TRANSEPITHILIAL TRANSPORT

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TUBULAR REABSORPTION

Trans epithelial transport of substance involves 5 steps:

1. Substance must leave tubular fluid by crossing luminal membrane of tubular cell.

2. Substance must pass through one side of tubular cell to the other.

3. Substance must cross basolateral membrane of tubular cell to enter interstitial fluid.

4. Substance must diffuse through the interstial fluid.

5. It must penetrate the capillary wall to enter blood plasma.

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THE IMPORTANCE OF SODIUM REABSORPTION

• In all nephron segments, the essential event for active transcellular

sodium reabsorption is the primary active transport of sodium from

cell to interstitial fluid by the Na-K-ATPase pumps in the basolateral

membrane.

• These pumps keep the intracellular sodium concentration lower than

in the surrounding media. The inside of the cell is negatively charged

with respect to the lumen, luminal sodium ions enter the cell passively,

down their electrochemical gradient.

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SODIUM REABSORPTION

Na+ reabsorption is active process i.e. requires Na+ - K+ ATPase pump in the basolateral membrane.

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SODIUM (NA+) REABSORPTION Na+ is reabsorbed throughout the tubule except descending

limb of Loop of Henle, because it is impermeable to Na+ Na+ Reabsorption in proximal convoluted tubule helps in

reabsorption of glucose, amino acid, H2O, Cl-, urea.

Na+ Reabsorption in Loop of Henle occurs with Cl- reabsorption.

Na+ Reabsorption in DCT and CT is under control of hormone Aldosterone.

In DCT and CT, 8% of filtered Na+ depends on Aldosterone for reabsorption. If no aldosterone, 20g of NaCl maybe lost per day.

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THE IMPORTANCE OF SODIUM REABSORPTION

Na+ is filtered and 99.5% of Na+ is reabsorbed in the tubule. Na+ reabsorption in different areas of tubule. Proximal convoluted tubule-- 65-67% Loop of Henle (thick ascending limb) – 25% Distal and Collecting Tubule – 8%

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Control of Aldosterone Secretion By K+ and Na+

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ROLE OF RENIN ANGIOTENSIN ALDOSTERONE SYSTEM (RAAS) IN VARIOUS DISEASES

RAAS activity if abnormally increased can cause hypertension. RAAS is also responsible for fluid retention and EDEMA occurring in

congestive heart failure. Angiotensin Converting Enzyme inhibitor – ACE inhibitor drugs are used

for hypertension and congestive heart failure.

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ROLE OF ATERIAL NATRIURETIC PEPTIDE (ANP) IN SODIUM (NA+) REABSORPTION Hormone ANP causes Na+ loss, therefore, decreases BP. Natriuretic means inducing Na+ loss in urine. Site of production of ANP – Atria of heart. Site of action of ANP – distal part of nephron (DCT and CT), causes decreased

Na+ reabsorption, therefore, increased Na+ and water loss in urine. Inhibits aldosterone secretion from adrenal cortex. Inhibits renin secretion, therefore, has negative effect on RAAS. Inhibits vasopressin secretion and its action, therefore causes decreased water

reabsorption. Dilates afferent arteriole and constricts efferent arteriole, therefore, increases GFR. Relaxes glomerular mesangial cells, therefore, increased Kf – increase GFR

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WATER REABSORPTION AND EXCRETION

Normal GFR 125ml/min or 180 liters/day 99 – 99.7% water is reabsorbed Average urine volume – 1 liter/day Minimum urine needed per day to get rid of waste products

500ml/day. Water is reabsorbed through water channels, made up of

proteins called Aquaporins. Proximal convoluted tubule (PCT) – 60-70%. It is passive,

due to osmotic gradient due to active reabsorption of solutes e.g. Na+

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WATER REABSORPTION AND EXCRETION Loop of Henle – 15% of water is reabsorbed. Descending limb of Loop of Henle [LH] is permeable to water but

ascending limb of Loop of Henle is impermeable to water. Because of this fluid in the descending limb of LH becomes hypertonic

and fluid in ascending limb of LH becomes hypotonic. Distal Convoluted Tubule (DCT) and Collecting Tubule (CT) – 20% of

filtered water is reabsorbed. DCT – 5% water reabsorbed. CT – 15% water reabsorbed.

• In DCT and CT, water is reabsorbed under the action of ADH (AntiDiuretic Hormone) or Vasopressin. ADH main site of action is CT

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WATER REABSORPTION AND EXCRETION ADH acts on DCT and CT. There are Aquaporin – 2 (protein

water channels) in DCT and CT, principal cells. Aquaporin – intracellular protein are stored in vesicles in the

cytoplasm of principal cells. Vasopressin causes rapid insertion of these vesicles in luminal

membrane of principal cells. This action of vasopressin (ADH) is mediated by binding of ADH

to V2 receptors.

V2 receptors are G-protein which activate cAMP – second messenger system.

As ADH causes water reabsorption in collecting tubules, fluid becomes hypertonic and urine passed is concentrated.

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24Mechanism of action of Vasopressin

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WATER REABSORPTION AND EXCRETION If no ADH, collecting tubule epithelium is relatively impermeable to water

in absence of ADH, therefore, large amount of dilute urine will be excreted.

Urine flow may increase to 15ml/min or 22liters/day. Diabetes Insipidus occurs due to deficiency of ADH

• Nephrogenic DI – occurs when V2 receptors in collecting tubule fail to respond to ADH.

• Central DI - occurs due to deficiency of ADH In both cases, person will pass dilute urine up to 22 liters/day

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PRESSURE NATRIURESIS, PRESSURE DIURESIS, OSMOTIC DIURESIS

The renal-body fluid system for arterial pressure control is a simple one:When the body contains too much extracellular fluid, the blood volumeand arterial pressure. The rising pressure in turn has a direct effect tocause the kidneys to excrete the excess extracellular fluid, thus returningthe pressure back toward normal.

An increase in arterial pressure in the human of only a few millimeters ofmercury can double renal output of water, which is called pressurediuresis, as well as double the output of salt, which is called pressure natriuresis. Osmotic Diuresis – high rate of water excretion caused by the filtrationof poorly reabsorbed solutes such as mannitol.

28WATER DIURESIS

29DECREASED WATER INTAKE

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REFERENCESHuman physiology by Lauralee Sherwood, seventh edition

Text book physiology by Guyton &Hall,11th edition

Text book of physiology by Linda .s contanzo, third edition