1. Metabolic Function
Of The Kidney

4. Urine Formation Filtration Reabsorption Secretion
GFR  125 ml/min = 180 litres per day
Urine Formation Rate: 1 ml/min (1.5 L/day)

7. Metabolic Function Of The Kidney
Excretion: (non-volatile) metabolic end products (e.g. urea, uric acid, creatinine, NH4+) and “foreign” solutes (e.g. some drugs)
fluids & electrolytes
Balance
Metabolic conversions
Acid-base balance
Production and secretion of enzymes (e.g., renin) & hormones (Vit. D & erythropoietin)

8. Energy supply for The Kidney

9. The kidney tissue represents less than 0.5% of the body weight

10. It recieves 25% of the cardiac output and 10% of O2 consumption.
COP
body
weight

11. It recieves 25% of the cardiac output and 10% of O2 consumption.
WHY?
body
weight
This is required for the synthesis of ATP needed to reabsorb most of the solutes filtered through glomerular membranes.

12. Very Low Energy Reserves
Glycogen
Phosphocreatine
Neutral lipids
Very Low Energy Reserves So
kidney must get its energy requirement from circulating substrates.

13. Substrates used by kidney for energy production?
Fed State
Starvation

14. Substrates used by kidney for energy production
Fed State
Oxidation
Glucose
Lactate

15. Substrates used by kidney for energy production
blood lactate glucose
Starvation
Blood fatty acid & ketone body concentrations
major kidney fuels during starvation.

16. Carbohydrate metabolism in the kidney
Gluconeogenesis ,
Glucose Oxidation
Glycolysis,
Citric acid cycle
HMS
Fructose metabolism

17. KIDNEY & GLUCOSE HOMEOSTASIS

18. Regarding glucose homeostasis, the kidney can be considered as 2 organs due to the differences in the distribution of various enzymes in renal medulla and renal cortex.
Renal cortex
Renal medulla
Glucose synthesis
Glucose utilization

19. Cells of the Renal Medulla
have considerable glucose-phosphorylating enzymes (hexokinase), glycolytic enzyme activity, So, can take up, phosphorylate and metabolize glucose through glycolysis,
depend on glucose as a major source of energy
The cells don’t have glucose-6-phosphatase and other gluconeogenic enzymes.
they can form glycogen, but cannot release free glucose into the circulation.

20. Cells of the renal cortex
the cells have gluconeogenic enzymes,
have little phosphorylating enzymes,
cannot synthesize appreciable concentrations of glycogen under normal conditions,
So, we can say that 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 and lactate, followed by glycerol. While alanine is preferentially used by the liver

21. Renal glucose metabolism in the postprandial conditions
After meal ingestion
There is decrease in gluconeogenesis
glucose is mainly utilized by brain, liver & muscles.
Renal glucose uptake is < 10% of the ingested glucose.
Renal gluconeogenesis paradoxically increases &it accounts for 50% of the endogenous glucose release.
DIABETES CARE, VOLUME 24, NUMBER 2, FEBRUARY 2001

22. Renal gluconeogenesis paradoxically increases
WHY?
postprandially
due to:
Postprandial increases in sympathetic nervous system activity
availability of gluconeogenic precursors (e.g., lactate and amino acids).
This increase in renal gluconeogenesis help liver glycogen repletion by suppression of hepatic glucose release.

23. Hormonal control of renal gluconeogenesis
Insulin: Decreases renal gluconeogenesis by:
Shunting precursors away from gluconeogenic pathway and diverting them into the oxidative pathway.
Decreasing renal free fatty acid uptake
Glucagon: has no effect on renal gluconeogenesis
*The mechanism is mediated through free fatty acids released during lipolysis accompanying hypoglycemia.
Epinephrine: has more effect on renal gluconeogenesis than hepatic gluconeogenesis (may be due to the rich autonomic innervations of the kidney).

24. After a 60-h fasting
Early increase in glucose release is mainly caused by hepatic glycogenolysis,
later it is mainly a result of gluconeogenesis.
Renal glucose uptake is reduced .
Renal glucose release increased

25. After a 60-h fasting
Hepatic glucose release decreased by 25%
So, liver cannot compensate for the kidney to preserve normoglycemia in patients with renal insufficiency during prolonged fasting.
This may explain why patients with renal failure develop hypoglycemia.

26. Lipid metabolism in kidney
The kidney has active glycerol kinase enzyme
It is a site for
B-Oxidation.
synthesis of carnitine .
ketolysis.
denovo synthesis of cholesterol
denovo synthesis of fatty acids.

27. Protein metabolism in the kidney:
The Kiney is a site for
urea synthesis.
site for creatine formation glycine & arginine.
Oxidative deamination and transdeamination of individual amino acids.
Oxidative deamination catalyzed by : Amino acid oxidases Transdeamination (L-Glutamate dehydrogenase)
major site for the action of glutaminase enzyme with its great role in acidosis.

29. Synthesis of creatine:
Amidine group from arignine Guanidnoacetate is first formed in kidneys from arginine and glycine, then it is methylated to form creatine in liver.

30. 1 2

31. Ammonia Formation f

32. Other Metabolic Function Of The Kidney
Ammonia Production In The Kidney
In the renal tubules by the action of the enzymes:
glutaminase and
L-glutamate dehydrogenase.
It combines with H+ to form ammonium ions: NH3 + H+ ↔NH4+

33. NH3 + H+ ↔NH4+
This reaction is favored at the acid pH of urine.
The formed NH4+ in the tubular lumen can not easily cross the cell membranes and is trapped in the lumen to be excreted in urine with other anions such as phosphate, chloride and sulphate.
NH4+ production in the tubular lumen accounts for about 60 % excretion of hydrogen ions associated with nonvolatile acids.

34. The H+ required for NH4+ formation comes from:
Glomerular filtrate
The effect of carbonic anhydrase enzyme during the synthesis of carbonic acid in the tubular cells, these H+ are secreted into the lumen by the Na+/ H+ exchanger.

37. In renal insufficiency, the kidneys are unable to produce enough NH3 to buffer the nonvolatile acids leading to systemic acidosis

38. Production of Erythropoietin (EPO)
It is a glycoprotein hormone that controls erythropoiesis.
It is produced by the renal cortex in response to low oxygen levels in the blood

39. In renal insufficiency
There is decreased production of erythropoietin, leading to anemia which is one of the major features in renal insufficiency.

40. Active vitamin D
One of the major metabolic function of the kidney is formation of the active form of vitamin D.
The key regulatory enzyme in vitamin D formation is the 1ά-hydroxylase enzyme

42. In renal failure patients and hemodialysis
the formation of vitamin D is greatly diminished leading to hyperparathyroidism.

43. RAS
Changes in renin ultimately alter the output of this system, principally the hormones angiotensin II and aldosterone.
Each hormone acts via multiple mechanisms, but both increase the kidney's absorption of sodium chloride, thereby expanding the extracellular fluid compartment and raising blood pressure.