Biochemistry of kidney and urine

Two layers: external – cortex, inner – medulla. 2

Functional-structural unit – nephron. Every kidney – about 1000000 nephrons. 3

RENAL FUNCTIONS Excretion of the end products from the organism (formation of urea) Maintenance of acidic-base balance Maintenance of water-salt balance Maintenance of osmotic pressure -Hormonal activity rennin synthesis (blood pressure regulation) erythropoietin (erythrocytes formation), 1,25-dihydroxycholecalcipherol (vitamin D3) Regulation of blood pressure Metabolism of proteins, lipids, carbohydrates, energetic metabolism 4

Metabolism in kidneys 80 % of water about 10 % of all oxygen 700-900 L of blood/day (25 %) carbs – main energetic material Active: Glycolysis Ketolysis Transamination and deamination 5

Urine formation Structures responsible for the urine formation: glomeruli, proximal canaliculi, distal canaliculi. Mechanism of urine formation: filtration reabsorption secretion 6

Mechanisms of elimination: filtration reabsorption excretion 7

Filtration About 120 mL/min or 180 L/day of blood is filtrated. Takes place in glomeruli. Substances with molecular mass below 40,000 Da pass through the membrane of glomerulus into capsula. About 120 mL/min or 180 L/day of blood is filtrated. Filtration – passive process. After filtration – primary urine (180 L/day) 8

Filtration is caused by: -hydrostatic pressure of blood in capillaries of glomeruli (70 mm Hg) -oncotic pressure of blood plasma proteins (30 mm Hg) -hydrostatic pressure of ultrafiltrate in capsule (20 mm Hg) 70 mm Hg-(30 mm Hg+20 mm Hg)=20 mm Hg Hydrostatic pressure in glomeruli is determined by the ratio between diameter of ascendant and descendant arteriole 9

Reabsorption Takes place in proximal and distal canaliculi. What is reabsorbed? Glucose (100%), amino acids (93%), water (98%), NaCl (70%) etc. The urine is concentrated (toxins damages the proximal canaliculi) Reabsorption: active passive. Lipophilic substances - passive. Na/K АТP-аse is very active 10

Secretion Takes place in proximal and distal canaliculi. Secretion: Transport of substances from blood into filtrate. Takes place in proximal and distal canaliculi. Secretion: active passive. Passive secretion depends on the pH. What is secreted? Ions of K, аmmonia, H+ drugs xenobiotics 11

CLEARANCE Clearance = (C urine/C plasma) * V Clearance of any substance is expressed in ml of blood plasma that is purified from this substance for 1 min while passing through the kidneys. About 180 L of primary urine is formed for 1 day, about 125 mL of primary urine for 1 min. Glucose is reabsorbed completely; clearance = 0 Inulin is not reabsorbed absolutely; clearance = 125 mL/min If clearance is more than 125 mL/min the substance is secreted actively. Clearance = (C urine/C plasma) * V 12

REGULATION OF BLOOD PRESUURE BY KIDNEYS 13

The increase of blood pressure REGULATION OF BLOOD PRESSURE BY KIDNEYS Inadequate supply of blood to kidneys (decrease of blood pressure, hypovolemia) Constriction of arterioles Irritation of juxtaglomerular cells Rhenin Angitensinogen Angiotensin І Angiotensin-converting enzyme Secretion of aldosteron Angiotensin ІІ Reabsorption of Na and water Vasocostriction The increase of blood volume The increase of blood pressure 14

REGULATION OF BLOOD PRESSURE BY KIDNEYS The decrease of blood pressure, hypovolemia The decrease of blood volume in atriums and carotid sinuses Reaction of volume-receptors Impulses to hypothalamus Stimulation of vasopressine formation Activation of hyaluronidase in kidneys canaliculi Depolimeralisation of hyaluronic acid The increase of water reabsorption The increase of blood volume The increase of blood pressure 15

MAINTAINING OF ACIDIC-BASE BALANCE BY KIDNEYS Three mechanisms: Conversion of two substituted phosphates into one substituted in the cavity of canaliculi Formation of carbonic acid in the cells with the following dissociation to Н+ and НСО3- ammonia excretion 16

MAINTAINING OF ACIDIC-BASE BALANCE BY KIDNEYS Cells of canaliculus Blood Cavity of canaliculus Na2HPO4 Na+ Na+ Na+ Na+ HPO42- H+ H+ NaH2PO4 17

MAINTAINING OF ACIDIC-BASE BALANCE BY KIDNEYS Cells of canaliculus Blood Cavity of canaliculus NaHCO3 Na+ Na+ Na+ H+ H+ HCO3- HCO3- H2CO3 H2CO3 H2O + CO2 H2O CO2 18

MAINTAINING OF ACIDIC-BASE BALANCE BY KIDNEYS Cells of canaliculus Blood Cavity of canaliculus Glutamine NH3 NH3+H+ Glutamic acid NH4+ 19