KIDNEYS CLINICAL BIOCHEMISTRY Two layers external cortex inner

KIDNEYS CLINICAL BIOCHEMISTRY

Two layers: external – cortex, inner – medulla.

Functionalstructural unit – nephron. Every kidney – about 1000000 nephrons.

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

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

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

Mechanisms of elimination: § filtration § reabsorption § excretion

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

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

Reabsorption Takes place in proximal and distal canaliculi. What is reabsorbed? Glucose (100%), amino acids (93%), water (98%), Na. Cl (70%) etc. The urine is concentrated (toxins damages the proximal canaliculi) Reabsorption: §active §passive. Lipophilic substances - passive. Na/K АТP-аse is very active

Secretion Transport of substances from blood into filtrate. Takes place in proximal and distal canaliculi. Secretion: §active §passive. Passive secretion depends on the p. H. What is secreted? • Ions of K, аmmonia, H+ • drugs • xenobiotics

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 m. L of primary urine for 1 min. Glucose is reabsorbed completely; clearance = 0 Inulin is not reabsorbed absolutely; clearance = 125 m. L/min If clearance is more than 125 m. L/min the substance is secreted actively. Clearance = (C urine/C plasma) * V

REGULATION OF BLOOD PRESUURE BY KIDNEYS

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

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 Impulses to hypothalamus Stimulation of vasopressine formation 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

MAINTAINING OF ACIDIC-BASE BALANCE BY KIDNEYS 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 Blood Cells of canaliculus Cavity of canaliculus Na 2 HPO 4 Na+ Na+ HPO 42 - H+ H+ Na. H 2 PO 4

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

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

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

Active form of vitamin D -1, 25 -dihydroxycholecalciferol is formed in kidneys 1, 25 -dihydroxycholecalciferol

PROPERTIES OF URINE Amount – 1500 -2000 m. L/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

Density – 1, 003 -1, 035 g/m. L Increased density – organic or inorganic substances available (diabetes mellitus) Decreased density – diabetes insipidus Isostenuria – continuously low density in oliguria (kidney failure) p. H – 5. 5 -6. 8 Acidic – meat food, diabetes mellitus, starvation, fever Alkaline – plant food, cystitis, pyelitis

PATHOLOGICAL COMPONENTS IN URINE Hematuria 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 Macrohematuria Microhematuria

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

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

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

PATHOLOGICAL COMPONENTS IN URINE Urobilinuria – appearance of urobilin in urine Brown color of urine - urobilinuria 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 Phenylketonuria Appearance of phenylpyruvate in urine Phenylketonuria - genetically determined disease which is caused by an absence or deficiency of phenylalanine hydroxylase Fe. Cl 3 test