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Metabolic Functions of The Kidney. Urine Formation FiltrationReabsorption Secretion 180 L / day Glomerular Filtration Rate (GFR) = 125 ml/min = 180.

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Presentation on theme: "Metabolic Functions of The Kidney. Urine Formation FiltrationReabsorption Secretion 180 L / day Glomerular Filtration Rate (GFR) = 125 ml/min = 180."— Presentation transcript:

1 Metabolic Functions of The Kidney

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4 Urine Formation FiltrationReabsorption Secretion 180 L / day Glomerular Filtration Rate (GFR) = 125 ml/min = 180 L / day 1.5 L / day Urine Formation Rate = 1 ml/min = 1.5 L / day

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7 Acid-basebalance Enzyme production & Endocrinal role 1- Production of certain enzymes(e.g. renin) 1- Production of certain enzymes (e.g. renin) 2- Endocrinal roles: Activation of vitamin D Activation of vitamin D Production of erythropoietin Production of erythropoietin Excretion of Metabolic End Products e.g. ammonia, urea, creatinine, uric acid & some ‘foreign’ molecules as drugs MetabolicConversions Fluids & Electrolytes Balance Metabolic Functions of the Kidney

8 Kidneys receive 25 % of the cardiac output & 10 % of O 2 consumption 25% of COP bodyweight Kidney tissue represents less than 0.5% of the body weight This is required for the synthesis of ATP needed to reabsorb most of the solutes filtered through glomerular membranes

9 Glycogen Phosphocreatine (CP) Lipids are very low energy stores kidney must get its energy requirement from circulating fuel substrates (as glucose, fatty acids & ketone bodies) So

10 Substrates used by kidney for energy production Fed State Starvation Fatty acids oxidation& ketone bodies degradation(ketolysis) Glucose oxidation Glycolysis& citric acid cycle citric acid cycle

11 Glycolysis, citric acid cycle &PPP, Glucose oxidation Gluconeogenesis Synthesis of glucose from non- carbohydrate sources as lactate, glycerol & amino acids (esp. glutamine) Fructose metabolism Carbohydrate Metabolism in the kidney

12 Kidney & glucose homeostasis The kidney can be considered as 2 organs due to the differences in the distribution of various enzymes in renal medulla & renal cortex Renal medulla Renal cortex Glucose utilization Glucose synthesis hexokinase (of glycolysis) Cells of the medulla have considerable amounts of hexokinase (of glycolysis). So, they can take up, phosphorylate & metabolize glucose through glycolysis BUT BUT: don’t have gluconeogenic enzymes They can form glycogen (limited amounts), but cannot release free glucose into the circulation. gluconeogenic enzymes Cells of the cortex have considerable amounts gluconeogenic enzymes, BUT BUT: have little hexokinase So, the release of glucose by the normal kidney is exclusively, a result of renal cortical gluconeogenesis. The most important substrates for renal gluconeogenesis are glutamine, lactate & glycerol

13 Hormonal control of renal gluconeogenesis Insulin Decreases renal gluconeogenesis by: Shunting precursors away from gluconeogenic pathway & diverting them into the oxidative pathways (glycolysis & PPP) Epinephrine Epinephrine : morestimulating renal gluconeogenesis has more effect on stimulating renal gluconeogenesis than hepatic gluconeogenesis (may be due to the rich autonomic innervations of the kidney). Glucagon no has no effect on renal gluconeogenesis

14 Kidney & Glucose Metabolism in Fasting Early fasting (first hours): liver glycogenolysis Source of glucose in blood is mainly by liver glycogenolysis 18 – 60 hours of fasting: gluconeogenesis (in liver & kidneys) Source of blood glucose is mainly gluconeogenesis (in liver & kidneys) After 60 hours of fasting: Liver gluconeogenesis release is decreased by 25% So, liver cannot compensate for the kidney to preserve normal blood glucose levels in patients with renal insufficiency during prolonged fasting. renal failure hypoglycemia This may explain why patients with renal failure develop hypoglycemia

15 Lipid Metabolism in the Kidney Lipid metabolic pathways occur in the kidneys: 1-  -oxidation of fatty acids  1-   -oxidation of fatty acids 2- Synthesis of carnitine : for transport of FA to mitochondria for oxidation 2- Synthesis of carnitine : for transport of FA to mitochondria for oxidation 3- De-novo synthesis of fatty acids 3- De-novo synthesis of fatty acids 4- Degradation of ketone bodies (Ketolysis) 4- Degradation of ketone bodies (Ketolysis) 4- De-novo synthesis of cholesterol 4- De-novo synthesis of cholesterol 5-Activation of glycerol to glycerol 3-phosphate (by glycerol kinase) 5- Activation of glycerol to glycerol 3-phosphate (by glycerol kinase)

16 Protein Metabolism in the Kidney Amino acid metabolic pathways occur in the kidneys: Excretion of ammonia & urea to urine 1- Excretion of ammonia & urea to urine Ammonia & urea are products of amino acid metabolism Degradation of glutamine by glutaminase enzyme 2- Degradation of glutamine by glutaminase enzyme G lutamine produced in most organs (from amino acid metabolism) are degraded into glutamate & ammonia in the kidney. acid base balance Ammonia produced is important in acid base balance Amino acids deamination 3- Amino acids deamination Creatine synthesis (first step) 4- Creatine synthesis (first step) from amino acids glycine & arginine

17 1 2 Formation of guanido acetic acid From amino acids glycine & argenine In the kidney Methylation of guanido acetic acid to creatine in the liver Synthesis of Creatine by kidneys & liver

18 Ammonia (NH 3 ) is produced in cells of renal tubules: By the enzymes: Glutaminase (as discussed before) Glutamate dehydrogenase In the tubular lumen, NH 4 + is produced from ammonia (NH 3 ) & H + : Ammonia (NH 3 ) + Hydrogen ions (H + ) = Ammonium ions (NH 4 + ) This reaction is favored at the acid pH of urine. can not The formed NH4+ in the tubular lumen can not easily cross the cell membranes & is trapped in the lumen to be excreted in urine with other anions such as phosphate, chloride & sulphate.(forming ammonium phosphate, ammonium chloride & ammonium sulphates). NH4+ production in the tubular lumen accounts for about 60% excretion of hydrogen ions associated with nonvolatile acids. Ammonia metabolism & acid base balance in the kidney

19 Source of H+ required for NH4+ formation: 1.Glomerular filtrate 2.The effect of carbonic anhydrase enzyme 2.The effect of carbonic anhydrase enzyme during the synthesis of carbonic acid in the tubular cells, H+ is secreted into the lumen by the Na+/ H+ exchanger. In renal insufficiency, the kidneys are unable to produce enough NH3 to buffer the nonvolatile acids leading to metabolic acidosis

20 Production of Erythropoietin Erythropoietin: It is a glycoprotein hormone that controls erythropoiesis. It is produced by the renal cortex in response to low oxygen levels in the blood In renal insufficiency In renal insufficiency : anemia There is decreased production of erythropoietin, leading to anemia which is one of the major features in cases of renal insufficiency.

21 Activation of vitamin D in the Kidney Renal 1  hydroxylase 1  hydroxylase enzyme The key regulatory enzyme in vitamin D activation is the 1  hydroxylase enzyme produced by the kidney. Vitamin D3 (cholecalceferol) is hydroxylated in the liver to 25 hydroxycholecalciferol (25 HCC) 1, 25 dihydroxycholecalceferol (1, 25 Then, the renal 1  hydroxylase converts 25 HCC to 1, 25 dihydroxycholecalceferol (1, 25 DHCC) DHCC), which is the active form of vitamin D. 1, 25 DHCC) The main physiological role of active vitamin D (1, 25 DHCC) is promoting calcification of bones (adding calcium) mainly through increasing calcium absorption from GIT. In renal insufficiency, notrenal rickets Active vitamin D is not sufficient ending in renal rickets (poor calcification of bones). hyperparathydroidism The resulting hypocalcemia due to vitamin D deficiency may end in hyperparathydroidism i.e. increased production of the parathyroid hormone (PTH).

22 Activation of vitamin D

23 Role of the Kidney in Electrolytes Balance Electrolyte balance (Na+ & K+) BY: Renin-Angiotensin System BY: Renin-Angiotensin System Angiotensinogen (in liver, inactive) Renin (synth. by kidney) (synth. by kidney) Angiotensin Angiotensin I Angiotensin Converting Enzyme Angiotensin Converting Enzyme (ACE) Angiotensin II Angiotensin II simulate aldesterone release (from adrenal cortex) simulate aldesterone release (from adrenal cortex) In Tubules of kidney Decrease Na+ excretion Increase K+ excretions Hypernatremiahypokalemia Increase BP

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