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TUBULAR REABSORPTION - 1Lecture – 3

Dr. Zahoor

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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.

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TUBULAR REABSORPTION

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TUBULAR REABSORPTION GFR is 125ml/min, out of this 124ml/min

is reabsorbed. 1ml/min is excreted.

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

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TUBULAR REABSORPTION In tubule, there is passive and active

reabsorption of different substances.

What is Passive Reabsorption? 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.

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TUBULAR REABSORPTIONWhat is Active Reabsorption? 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

-3)

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Steps of Transepithilial transport

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TUBULAR REABSORPTIONWhat is Trans epithelial transport of substance? It involves following 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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TUBULAR REABSORPTIONWe will discuss Na+ reabsorption.

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

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Sodium Reabsorption

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Na+ 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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OVERALL HANDLING

OF NA+

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Na+ REABSORPTION 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.

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Na+ REABSORPTION IMPORTANT Na+ is reabsorbed throughout the tubule

except descending limb of Loop of Henle, because it is impermeable to Na+

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Na+ REABSORPTION Na+ reabsorption in DCT and CT is

under control of hormone Aldosterone. With Na+, Cl- is passively absorbed

down its concentration gradient.

We will study Renin-Angiotensin-Aldosterone System (RAAS) and Atrial Natriuretic Peptide in regulation of sodium.

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Dual Control of

Aldosterone Secretion By K+ and Na+

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Renin Angiotensin Aldosterone

System (RAAS)

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Na+ REABSORPTION IN DCT & CT There are 2 types of cells located in DCT and CT i. Principal Cells ii. Intercalated Cells

Where Aldosterone acts in DCT and CT?Aldosterone acts on Principal Cells They are in large number and Aldosterone acts on

them and causes Na+ reabsorption and K+ secretion.

Main site of action of Aldosterone is DCT and CT.

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Na+ REABSORPTIONii. Intercalated Cells They are concerned with acid base

balance and we will discuss later.

IMPORTANT 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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APPLIEDRole 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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APPLIED Drugs that affect Na+ reabsorption 1. Diuretics - They cause diuresis (increased urinary output)

by inhibiting tubular reabsorption of Na+. - As Na+ is lost, more water is lost, therefore, they

help to remove excess extra cellular fluid.

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ATERIAL NATRIURETIC PEPTIDE (ANP) 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.

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ATERIAL NATRIURETIC PEPTIDE (ANP) (cont) Other action of ANP are - 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 & 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

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WATER REABSORPTION Water is reabsorbed through water

channels, made up of proteins called Aquaporins.

Water reabsorption in the tubule 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 Loop of Henle – 15% of water is reabsorbed

IMPORTANT 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

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Osmolarity of fluid

in different segment

s of tubule

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WATER REABSORPTION Distal Convoluted Tubule (DCT) and Collecting

Tubule (CT) – 20% of filtered water is reabsorbed. DCT – 5% water reabsorbed CT – 15% water reabsorbed

IMPORTANT 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 REABSORPTIONADH 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

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WATER REABSORPTION 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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Mechanism of action of Vasopressin

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ADH OR VASOPRESSIN ADH is hormone synthesized in

hypothalamus, supraoptic nuclei mainly, but also in para- ventricular nuclei

They have axonal connection to posterior pituitary

ADH once synthesized in hypothalamus is transported via axon to posterior pituitary and stored there in posterior pituitary.

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WATER REABSORPTIONQ. If ADH is absent, what will happen? 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.

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APPLIEDDIABETES INSIPIDUSDiabetes Insipidus [DI] is of 2 types:1. Central DI - occurs due to deficiency of

ADH2. Nephrogenic DI – occurs when V2

receptors in collecting tubule fail to respond to ADH

In both cases, person will pass dilute

urine up to 22 liters/day

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WATER DIURESIS

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BODY RESPONSE

TO DECREASED

WATER INTAKE

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IMPORTANT POINTS1. Water reabsorption is by osmosis and is

dependent upon Na+ reabsorption, but water absorption depends on ADH in DCT and CT

2. Na+ is absorbed actively by all tubular segments except descending limb of Loop of Henle, which is impermeable to Na+.

3. Descending limb of LH is permeable to water, but ascending limb of LH is impermeable to water

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