Biochemistry of Kidney PDF

# Biochemistry of Kidney ## Kidney (with nephron enlarged) A diagram of a kidney with an enlarged nephron is displayed. The kidney has an inner medulla and an outer cortex the nephron is labelled with the following: * Unfiltered blood * Filtered blood * Ureter * Urine exits to bladder The nephro...

# Biochemistry of Kidney ## Kidney (with nephron enlarged) A diagram of a kidney with an enlarged nephron is displayed. The kidney has an inner medulla and an outer cortex the nephron is labelled with the following: * Unfiltered blood * Filtered blood * Ureter * Urine exits to bladder The nephron is highlighted with the following labels: * Proximal tubule * Distal tubule * Urine exits duct ## Functions of the Kidney * Regulation of the water and electrolyte content of the body * Retention of substances vital to the body * Maintenance of acid/base balance * Excretion of waste products, water soluble toxic substances and drugs * Endocrine functions ## Urine is formed as a result of a three-phase process * Glomerular filtration * Selective (active) and passive reabsorption * Secretion ## Glomerular filtration * 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. * At the same time, many other low molecular weight constituents are reabsorbed by active transport - glucose, AA and organic and inorganic ions. ## Proximal Tubule * Reabsorbs 60% of all solute (100% of glucose and AA, 90% of bicarbonate, 80-90% of inorganic phosphate and water. ## Loop of Henle * Next reabsorption of NaCl * In descending loop of Henle * Resorption of water by osmosis * Increasing of osmolarity (hypertonic) * In ascending loop of Henle * Active transport of NaCl out of the tubule * Decreasing of osmolarity (hypotonic) ## Distal Tubule and Collecting Ducts * Aldosterone promotes Na+ ions and water reabsorption * Excretion of H+ ions * The final concentration of urine depends upon antidiuretic hormone (ADH). ## Secretion * 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. ## Energy for the transport * ATP is derived from the oxidative metabolism of glucose, lactate, pyruvate, fatty acids, glycerol, citrate and AA absorbed from the blood. ## The nephron A diagram of a nephron is shown. * The nephron has a glomerulus, proximal tubule, loop of Henle, distal tubule and collecting duct. ## Maintenance of acid-base balance ### Proton secretion * The tubule cells absorb CO2 from the blood and then hydrate it to carbonic acid (carbonate dehydratase). * Carbonic acid then dissociates to HCO3- and H+. * H+ is exported to the urine by an ATP-driven membrane-localised transport system, while HCO3- returns to the blood. A diagram of the process of proton secretion in the kidney is presented. * The diagram shows a renal tubule cell with the interstitial fluid on one side and the tubular lumen on the other. * CO2 and water are transported into the cell where carbonic anhydrase acts on them to create carbonic acid. * Carbonic acid then dissociates to HCO3- and H+. * HCO3- is transported out of the cell into the interstitial fluid while H+ is transported into the tubular lumen. ### Maintenance of acid-base balance A diagram is presented illustrating the process of ammoniagenesis. * Glutamine is converted to glutamic acid and ammonia by glutaminase. * Glutamate dehydrogenase acts on glutamate and NAD+ to produce alpha-ketoglutarate and NADH and H+. * Ammonia reacts with H+ to form ammonium. ## Endocrine function of kidney ### Hormones of the kidney * Erythropoietin * Calcitriol * Angiotensin ## The role of kidney in hormonal regulation A diagram illustrating the interaction of the kidney and other glands/organs is presented. * The kidney receives input from the following glands/organs * Hypophysis * Parathyroid gland * Adrenal cortex * The kidney produces the following hormones * Erythropoietin * Calcitriol * The kidney activates angiotensinogen to angiotensin I which then converts to angiotensin II. ## Erythropoietin * Polypeptide hormone 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 pO2). * The hormone 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 hormone involved in calcium homeostasis. * It is formed in the liver from calcidiol by hydroxylation at C-1. * The activity of hydroxylase (calcidiol-1-monooxygenase) is regulated by the hormone parathyrin (parathormone). ## Renin - angiotensin system * 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. * Release of aldosterone. * Increased release of ADH. * Thirst * The opposite occurs when fluid overload occurs. ## The hormones interact when blood loss or dehydration occurs to maintain intravascular volume A diagram is presented illustrating the mechanism by which hormones interact to maintain intravascular volume. * When blood loss occurs, arterial pressure decreases, which leads to a decrease in GFR. * This stimulates the secretion of renin, which in turn increases the levels of angiotensin II. * Angiotensin II increases the release of ADH and aldosterone which in turn increase water retention. * Also, angiotensin II causes vasoconstriction which increases blood pressure. * Thirst also helps by stimulating water intake. ## END