Biochemistry of kidney Functions of the Kidney Regulation

Biochemistry of kidney

Functions of the Kidney Regulation of the water and electrolyte content of the body. n Retention of substances vital to the body n Maintenance of acid/base balance. n Excretion of waste products, water soluble toxic substances and drugs. n Endocrine functions n

Urine is formed as a result of a three phase process Glomerular fitration n Selective (active) and passive reabsorption n Secretion n

Glomerular filtration n n Filtration takes place through the semipermeable walls of the glomerular capillaries The driving hydrostatic pressure is provided by arterial pressure About 20% of renal plasma flow is filtered each minute (~ 125 ml/min) GFR Result is glomerular filtrate GF (primary urine) (~ 150 l).

Reabsorption In the proximal and distal tubule, the GF becomes highly concentrated as the result of the removal of water. n At the same time, many other low molecular weight constituents are rebsorbed by active transport – glucose, AA and organic and inorganic ions n

Secretion n Some of the substances that have to be excreted from the body are released into urine in the kidney by active transport – H+ and K+ ions, urea, creatinine and drugs.

Proximal Tubule n Reabsorbs 60% of all solute (100% of glucose and AA, 90% of bicarbonate, 8090% of inorganic phosphate and water.

Loop of Henle Next reabsorption of Na. Cl n In descending loop of Henle - resorption of water by osmosis - increasing of osmolarity (hypertonic) n In ascending loop of Henle - active transport of Na. Cl out of the tubule - decreasing of osmolarity (hypotonic) n

Distal Tubule and Collecting Ducts Aldosterone promotes Na+ ions and water reabsorption n Excretion of H+ ions n The final concentration of urine depends upon antidiuretic hormone (ADH). n

Energy for the transport n ATP is derived from the oxidative metabolism of glucose, lactate, pyruvate, fatty acids, glycerol, citrate and AA absorbed from the blood.

Constituents of the urine Organic constituents n Inorganic constituents n

Organic constituents urea creatinin uric acid hippurate glucose ketone bodies aminoacids proteins grams/day 20 – 30 1 – 1, 5 0, 3 – 2, 0 0, 15 < 0, 16 < 3 < 1 – 3 < 0, 15 Inorganic constituents Cl. Na+ K+ SO 42 NH 4+ HPO 42 Ca 2+ Mg 2+ mmol/day 120 – 240 100 – 150 60 – 80 30 – 60 30 – 50 10 – 40 4 – 11 3 – 6

Proton secretion The tubule cells absorb CO 2 from the blood and then hydrate it to carbonic acid (carbonate dehydratase). n Carbonic acid then dissociates to HCO 3 and H+. n H+ is exported to the urine by an ATPdriven membrane-localised transport system, while HCO 3 - returns to the blood. n

Ammonia excretion Ammonia is produced enzymatically from glutamine and other AA. n NH 3 combines with secreted H+ ions to form a nondiffusible ammonium ion (NH 4+) which is excreted in the urine. n Ammonia production is increased by a severe metabolic acidosis. n

Recycling of the calcium and phosphate ions Parathormone (parathyrin) n Calcitonin n Calcitriol n

Parathormone PTH (parathyrin) n n - A peptide hormone produced by parathyroid gland stimulates the absorption of calcium in the kidney at the same time inhibits the resorption of phosphate The overal effect of elevated PTH levels is an increase in plasma calcium level decline in plasma phosphate level

Calcitonin A peptide produced in C cells of the thyroid gland n Inhibits the reabsorption of both calcium and phosphate n The result is an overal decline in the plasma level of either ion n With to respect to calcium reabsorption, calcitonin is an antagonist of PTH n

Calcitriol Steroid hormone, formed in the kidneys n It has stimulatory effect on the reabsorption of both calcium and phosphate ions n

Reabsorption of sodium ions Aldosterone (steroid hormone) stimulates Na+ retention n Atrial natriuretic peptide (ANP), a hormone from the atrium of the heart inhibits retention of Na+. n Both hormones probably affect Na+/K+ ATPase n

Atrial Natriuretic Peptide (ANP) ANP is released when arterial pressure is increased (in heart failure) or fluid overload. n It promotes loss of Na+ and Cl- ions and water chiefly by increasing GFR. n

Antidiuretic Hormon (ADH) n n n ADH increases the water permeability of the distal tubule and collecting duct, thus increasing the concentration of urine. In contrast when secretion of ADH is inhibited, it allows dilute urine to be formed. This occures mainly, when plasma sodium concentration falls such as following drinking large quantities of water. This fall is detected by osmoreceptors in the hypothalamus.

Gluconeogenesis Chief substrate is glutamine n Other substrates are AA, lactose, glycerol or fructose (all are obtained from the blood plasma) n The ammonia derived from this AA serve to buffer the p. H of the urine. n Gluconeogenesis is induced by cortisol n

Glucose recycling Is an energy dependent process n Is independent of gluconeogenesis n Glucose uptake occurs as compulsatory cotransport with Na+ ions n It is driven by the concentration gradient of Na+ between the urine and interior of the cells (secondary active transport) n

Hormones of the kidney Erythropoietin n Calcitriol n Angiotensin n

Erythropoietin n n Polypeptide hormon that is formed predominantly by the kidney (also by the liver) It controls the differentiation of the bone marrow stem cells The release is stimulated by hypoxia (low p. O 2) The hormon ensures that the bone marrow cells are converted to erythrocytes, so that their concentration in the blood increases

Calcitriol 1 -alpha, 25 -dihydroxycholecalciferol is a steroid-related hormon involved in calcium homeostasis. n It is formed in the liver from calcidiol by hydroxylation at C-1 n The activity of hydroxylase (calcidiol-1 monooxygenase) is regulated by the hormone parathyrin (parathormone). n

Renin – angiotensin system n n n Renin is an enzyme which converts the plasma protein angiotensinogen to angiotensin I. Angiotensin converting enzyme (ACE) which is formed in the lungs converts angiotensin I to angiotensin II which causes vasoconstriction and an increase in blood pressure. Angiotensin II also stimulates the aldosterone production (water and sodium retention which together increase blood volume).

Renin increases the production of angiotensin II which is released when there is fall in intravascular volume and dehydration. This leads to: Constriction of the efferent arteriole to maintain GFR, by increasing the filtration pressure in the glomerules. n Release of aldosterone. n Increased release of ADH. n Thirst n The opposite occurs when fluid overload occurs. n