Lecture – 3 Dr. Zahoor 1

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. 2

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TUBULAR REABSORPTION 4

 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. 5

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. 6

TUBULAR REABSORPTION What 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 (PO 4 -3 ) 7

8 Steps of Transepithilial transport

TUBULAR REABSORPTION What 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. 9

TUBULAR REABSORPTION We will discuss Na+ reabsorption.  Na+ reabsorption is active process i.e. requires Na + - K + ATPase pump in the basolateral membrane. 10

11 Sodium Reabsorption

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 % - Loop of Henle (thick ascending limb) – 25% - Distal and Collecting Tubule – 8% 12

OVERALL HANDLING OF NA + 13

Na + REABSORPTION  Na + Reabsorption in proximal convoluted tubule helps in reabsorption of glucose, amino acid, H 2 O, Cl -, urea  Na + Reabsorption in Loop of Henle occurs with Cl - reabsorption.  Na + Reabsorption in DCT and CT is under control of hormone Aldosterone. 14

Na + REABSORPTION IMPORTANT  Na + is reabsorbed throughout the tubule except descending limb of Loop of Henle, because it is impermeable to Na+ 15

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. 16

17 Dual Control of Aldosterone Secretion By K+ and Na+

18 Renin Angiotensin Aldosterone System (RAAS)

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. 19

Na + REABSORPTION ii. 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. 20

APPLIED 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. 21

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. 22

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. 23

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 24

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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 26

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 + 27

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 28

29 Osmolari ty of fluid in different segment s of tubule

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 30

WATER REABSORPTION 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 31

WATER REABSORPTION  This action of vasopressin (ADH) is mediated by binding of ADH to V 2 receptors  V 2 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. 32

33 Mechanism of action of Vasopressin

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. 34

WATER REABSORPTION Q. 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. 35

APPLIED DIABETES INSIPIDUS Diabetes Insipidus [DI] is of 2 types: 1. Central DI - occurs due to deficiency of ADH 2. Nephrogenic DI – occurs when V 2 receptors in collecting tubule fail to respond to ADH  In both cases, person will pass dilute urine up to 22 liters/day 36

37 WATER DIURESIS

38 BODY RESPONSE TO DECREASED WATER INTAKE

IMPORTANT POINTS 1. 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 39

THANK YOU 40