הנפרון. Introduction to Physiology (Course # 72336) THE KINDEY regulation of water and inorganic ions. Adi Mizrahi

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1 Introduction to Physiology (Course # 72336) 1 THE KINDEY regulation of water and inorganic ions Adi Mizrahi mizrahia@cc.huji.ac.il הכליה עקרונות של תפקוד ומבנה בסיסיים 2 הנפרון הכליה רגולציית מים ויונים אינאורגנים 3 Balance is achieved primarily by control of urination מנעד גדול 1

2 הכליה רגולציית מים ויונים אינאורגנים 4 Both water and sodium are freely filtered in the renal corpuscle Na + Na + H 2 O Na Na + + Na H 2 O + H 2 O H 2O Na+ H 2O Na + Na + H 2 O Na + Na + H 2 O H 2 O הכליה רגולציית מים ויונים אינאורגנים 5 2/3 in proximal tubule Both water and sodium are highly reabsorbed but not secreted 1/3 in the rest of tubule but subject to physiological control הכליה רגולציית מים ויונים אינאורגנים 6 Sodium reabsorption is both an active process and a passive process Water reabsorption is a passive process (sodium-dependent) Differs in different parts of the Nephron 2

3 הכליה רגולציית נתרן Active reabsoption of sodium (from cell to interstitial fluid) is via the Na+/K+ ATPase pump and occurs similarly all along the tubule 7 הכליה רגולציית נתרן The passive process (from lumen to cell) is via different mechanisms along the tubule 8 Na+ glu Na+ symport antiport H+ Na + H + H + H + H + antiport Cl - Na+, Cl - diffusion Na +, K + 2Cl - symport Na+ Cl- Na+ symport Channel הכליה רגולציית מים 9 Water reabsorption is by diffusion (sodium reabsorption-dependent) 3

4 הכליה רגולציית מים 10 The level of water reabsorption is very different along the tubule High in proximal tubule Subject to physiological control Depends on the presence of aquaporins הכליה רגולציית מים The level of water reabsorption is controlled by ADH 11 More aquaporins inserted into the membrane Subject to physiological control + - Antidiuretic hormone (ADH) Vasopressin Less aquaporins inserted into the membrane הכליה רגולציית מים 12 Diabetes insipidus Failure of the pituitary to release ADH 4

5 הכליה ריכוז השתן The obligatory water loss 13 Waste products 600 mosmol/day Maximum urine concentration 1400 mosmol/l 600 mosmol/day 1400 mosmol/l = L/day What is the mechanism that allows to concentrate the urine so much? מהו המנגנון המרכז את השתן כאשר ADH הכליה ריכוז השתן גבוה? 14 15% of the nephrons are juxtamedullary with a loop of Henle Friedrich Gustav Jakob Henle ( ) Hyperosmotic urine הכליה ריכוז השתן 15 The countercurrent multiplier system isoosmotic Impermeable to water But permeable to NaCl hyperosmotic 5

6 הכליה ריכוז השתן 16 Impermeable to water But permeable to NaCl Impermeable to NaCl But permeable to water הכליה ריכוז השתן 17 The countercurrent multiplier system הכליה ריכוז השתן 18 ADH 6

7 הכליה ריכוז השתן The vasa recti help maintain the medullary hyerposmotic gradient 19 הכליה ריכוז השתן Urea recycling helps maintain the medullary hyperosmotic gradient 20 reabsorption facilitated diffusion reabsorption reabsorption הכליה רגולציית נתרן 21 Regulation of Na + Because Na+ is the major solute in the extracellular fluid it is directly linked to the extracellular volume (plasma volume) and thus - cardiovascular pressure. Low Na+ low volume low cardiovascular pressure High Na+ high volume high cardiovascular pressure 7

8 הכליה רגולציית נתרן 22 Na + is not secreted Na + excretion = Na + filtered Na + reabsorbed הכליה רגולציית נתרן 23 Regulation of Na + GFR Constriction of afferent arterioles P GC GFR GFR= K f (P GC -P BS - GC ) For example הכליה רגולציית נתרן 24 Regulation of Na + reabsorption Aldosterone (steroid hormone) What controls Aldosterone? 8

9 הכליה רגולציית נתרן 25 The reninangiotensin system הכליה רגולציית נתרן 26 The reninangiotensin system יש בשפע! גורם המגביל Na+ depletion Angiotensin II הכליה רגולציית נתרן 27 The reninangiotensin system

10 הכליה רגולציית נתרן and one more regulator 28 Atrial Natriuretic Peptide (ANP) Inhibits Na + reabsorption by Decreasing Aldosterone levels הכליה רגולציית מים Regulation of water reabsorption 29 What controls levels of ADH? Antidiuretic hormone (ADH) Vasopressin הכליה רגולציית מים Baroreceptors Osmoreceptors 30 Secondary pathway (activated only in extreme cases) Main pathway 10

11 לדוגמא... הכליה רגולציית מים ויונים אינאורגנים 31 הכליה רגולציית מים ויונים אינאורגנים 32 Water appetite הכליה רגולציית מים ויונים אינאורגנים Salt appetite 33 Built-in universal crave but no regulatory mechanism under normal physiological conditions 11

12 הכליה רגולציית מים ויונים אינאורגנים Potassium is freely filtered, it is reabsorbed and secreted! Regulation of Potassium 34 Mainly secretion is regulated K + excretion = K + filtered K + reabsorbed + K + secreted הכליה רגולציית מים ויונים אינאורגנים Regulation of Potassium 35 הכליה רגולציית מים ויונים אינאורגנים Regulation of Potassium 36 Potassium channels 12

13 הכליה רגולציית מים ויונים אינאורגנים Regulation of Potassium 37 Regulation of K + secretion is by aldosterone that drive increased uptake by the Na + /K + ATPase הכליה רגולציית מים ויונים אינאורגנים 38 In summary 39 Hydrogen ion regulation ph PH=7.4 ph [H + ] [H + ] Acidosis Alkalosis 13

14 40 Hydrogen ion regulation Is carried out by both the respiratory system and the urinary system 41 Hydrogen ion regulation Carbonic anhydrase CO +HO - +H 2 2 H 2 CO 3 HCO 3 + Carbonic acid Bicoarbonate Reminder 1 Hydrogen ion regulation Acids H + containing substances that dissociate in solution to produce H + Strong acids Greater tendency to dissociate (e.g. HCl). + Anion Bases Substance that can bind with free H + and remove it from the solution Strong bases Greater tendency to bind H + (e.g. NaOH). ph ph= log 1/[H] Low ph is a High acid A ph change of 1 = 10fold change in [H]

15 Reminder 2 Buffers Hydrogen ion regulation Mixture of compounds that minimizes ph changes when either an acid or a base is added (or removed) from a solution Extracellular fluid e.g. H +H 2 CO 3 HCO 3- + Carbonic acid Bicoarbonate Intracellular fluid Proteins, Phosphate buffers Hydrogen ion regulation 45 Hydrogen ion regulation [H + ] Three lines of defense 1. Buffers (immediate) 2. Pulmonary ventilation (minutes). [H+] CO2, reaction driven to the left CO 2 + H 2O H 2CO 3 HCO 3- + H + [H + ] 3. Kidneys (long term) 15

16 46 The kidneys regulate [H + ] by altering the plasma levels of bicarbonate Carbonic anhydrase CO 2 + H 2 O H 2 CO 3 HCO 3- + H + Carbonic acid When HCO - 3 increases, then [H + ] decreases When HCO - 3 decreases, then [H + ] increases Therefore Bicoarbonate When [H + ] decreases the kidney excretes HCO3 - When [H + ] increases the kidney produces HCO3-47 bicarbonate is freely filtered, it is reabsorbed and secreted! bicarbonate HCO - 3 excretion = HCO 3- filtered HCO 3- reabsorbed + HCO 3- secreted 1 Bicarbonate reabsorption 48 When [H + ] increases For each bicarbonate filtered, a bicarbonate is produced and reabsorbed into the plasma. Thus, No net bicarbonate change has occurred. H + ATPase pumps Na + /H + countertransporters 1 16

17 New bicarbonate (1) 49 When [H + ] increases further (and all bicarbonate has been used) H + ions are buffered by phosphate and excreted. Bicrabonate is gained New bicarbonate (2) 50 When [H + ] increases further NH 3 + H + NH When [H + ] decrease bicarbonate is excreted in the urine and its plasma concentration is decreased excreted Rate of H + secretion is lower 17

18 52 In summary 53 Two main categories to be recognized CO 2 + H 2 O H 2 CO 3 HCO 3- + H + Respiratory acidosis/alkalosis (hypo/hyper ventilation, disease) Metabolic acidosis/alkalosis (non respiratory) Exercise/diabetes/fasting 54 Two main categories to be recognized CO 2 + H 2 O H 2 CO 3 HCO 3- + H + Respiratory acidosis/alkalosis (hypo/hyper ventilation, disease) Metabolic acidosis/alkalosis (non respiratory) Exercise/diabetes/fasting 18