1. KIDNEYS CLINICAL BIOCHEMISTRY

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

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

4. RENAL FUNCTIONS -Excretion of the end products from the organism (formation of urine) -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 D 3 ) -Regulation of blood pressure -Metabolism of proteins, lipids, carbohydrates, energetic metabolism

5. 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

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

7. Mechanisms of elimination:  filtration  reabsorption  excretion

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

9. 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

10. Reabsorption:  active  passive. Lipophilic substances - passive. Na/K АТP-аse is very active 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)

11. 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 Secretion Transport of substances from blood into filtrate.

12. CLEARANCE 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

13. REGULATION OF BLOOD PRESUURE BY KIDNEYS

14. 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 ІІ Angiotensin-converting enzyme Vasocostriction The increase of blood pressure Secretion of aldosteron Reabsorption of Na and water The increase of blood volume

15. 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 Stimulation of vasopressine formation Impulses to hypothalamus 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

16. 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 НСО 3 - - ammonia excretion MAINTAINING OF ACIDIC-BASE BALANCE BY KIDNEYS

17. Cells of canaliculus BloodCavity of canaliculus Na 2 HPO 4 Na + HPO 4 2- Na + NaH 2 PO 4 Na + H+H+ H+H+ MAINTAINING OF ACIDIC-BASE BALANCE BY KIDNEYS

18. NaHCO 3 Na + HCO 3 - Na + H 2 CO 3 Na + H+H+ H+H+ H2OH2OCO 2 H2OH2O + H 2 CO 3 HCO 3 - Blood Cells of canaliculus Cavity of canaliculus MAINTAINING OF ACIDIC-BASE BALANCE BY KIDNEYS

19. NH 3 +H + Glutamine NH 4 + NH 3 Glutamic acid MAINTAINING OF ACIDIC-BASE BALANCE BY KIDNEYS Blood Cells of canaliculus Cavity of canaliculus

20. HORMONAL ACTIVITY (ERYTHROPOIETIN) Normal level of oxygen in blood The increased consumption of oxygen or decreased amount of erythrocytes The decrease of oxygen level in blood Formation of erythropoietin by kidneys Erythropoietin stimulation Bone marrow Intensified erythropoiesis Increased number of erythrocytes The increase of oxygen in blood

21. Active form of vitamin D - 1,25-dihydro- xycholecalci- ferol is formed in kidneys 1,25-dihydroxycholecalciferol

22. PROPERTIES OF URINE Amount – 1500-2000 mL/day Poliuria – diabetes mellitus and insipidus Oliguria – heart failure, nephritis, vomiting, fever Anuria – kidney failure, acute intoxication by heavy metals Color – straw-yellow Pale – poliuria (diabetes insipidud) Dark – jaundice, concentrated urine Red – blood available Green-blue – decay of proteins in the intestine Transparency – transparent Cloudy – pus or mucin available

23. Density – 1,003-1,035 g/mL Increased density – organic or inorganic substances available (diabetes mellitus) Decreased density – diabetes insipidus Isostenuria – continuously low density in oliguria (kidney failure) pH – 5.5-6.8 Acidic – meat food, diabetes mellitus, starvation, fever Alkaline – plant food, cystitis, pyelitis

24. PATHOLOGICAL COMPONENTS IN URINE Hematuria Macrohematuria Microhematuria Causes of hematuria Infectious diseases – glomerulonephrotis, pyelonephritis, prostatitis, uretritis, cystitis Stones in kidneys and urinary tracts Trauma of kidneys and organs of urinary tracts Tumors of kidneys and organs of urinary tracts – cancer of kidneys, bladder

25. PATHOLOGICAL COMPONENTS IN URINE Proteinuria Type Pathophysio- logic features Cause Glomerular Increased glomerular capillary permeability to protein Primary or secondary glomerulopathy Tubular Decreased tubular reabsorption of proteins in glomerular filtrate Tubular or interstitial disease Overflow Increased production of low- molecular-weight proteins Monoclonal gammopathy, leukemia Dehydration Emotional stress Fever Heat injury Inflammatory process Intense activity Most acute illnesses Orthostatic (postural) disorder COMMON CAUSES OF BENIGN PROTEINURIA

26. Physiological: · Alimentary – (in 30-60 min after carbohydrate food consumption. · Emotional (stress). Pathological: · Related to hyperglycemia: · Insular – deficit of insulin (diabetes mellitus, pancreatitis). · Extrainsular – disorders of thyroid gland, pituitary functions, liver diseases). · Not related to hyperglycemia – renal glycosuria (normal level of glucose in blood) (renal diabetes). PATHOLOGICAL COMPONENTS IN URINE Glycosuria

27. Condition where there is pus or too many white blood cells in the urine PATHOLOGICAL COMPONENTS IN URINE Pyuria Cloudy urine - pyuria Causes: Infectious diseases of kidneys or urinary tract (chlamydia, gonorrhea, viral infections, mycoplasma, fungal infections, tuberculosis), infection of the prostate Noninfectious causes treatment with glucocorticoids mechanical trauma kidney stones tumors (benign or malignant)

28. Brown color of urine - bilirubinuria Bilirubinuria – appearance of bilirubin in urine Is the result of direct (conjugated) bilirubin in blood Causes: mechanical jaundice parenchimal jaundice PATHOLOGICAL COMPONENTS IN URINE Bilirubinuria

29. Causes overburdening of the liver excessive RBC breakdown increased urobilinogen production a large hematoma restricted liver function hepatic infection poisoning liver cirrhosis PATHOLOGICAL COMPONENTS IN URINE Urobilinuria Urobilinuria – appearance of urobilin in urine Brown color of urine - urobilinuria

30. PATHOLOGICAL COMPONENTS IN URINE Phenylketonuria Appearance of phenylpyruvate in urine Phenylketonuria - genetically determined disease which is caused by an absence or deficiency of phenylalanine hydroxylase FeCl 3 test