KIDNEYS BIOCHEMISTRY

Two layers: external – cortex, inner – medulla.

Functional-structural 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 D3)

-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 materialActive:GlycolysisKetolysisTransamination 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

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.

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: activepassive. 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)

Takes place in proximal and distal canaliculi.

Secretion: activepassive.

Passive secretion depends on the pH.

What is secreted?•Ions of K, аmmonia, H+

•drugs•xenobiotics

Secretion

Transport of substances from blood into filtrate.

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

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 ІІ

Angiotensin-converting enzyme

Vasocostriction

The increase of blood pressure

Secretion of aldosteron

Reabsorption of Na and water

The increase of blood volume

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

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 НСО3

-

- ammonia excretion

MAINTAINING OF ACIDIC-BASE BALANCE BY KIDNEYS

Cells of canaliculusBlood Cavity of canaliculus

Na2HPO4

Na+Na+

HPO42-

Na+

NaH2PO4

Na+

H+ H+

MAINTAINING OF ACIDIC-BASE BALANCE BY KIDNEYS

NaHCO3

Na+

HCO3-

Na+

H2CO3

Na+

H+ H+

H2O CO2

H2O CO2+

H2CO3

HCO3-

BloodCells of

canaliculus Cavity of canaliculus

MAINTAINING OF ACIDIC-BASE BALANCE BY KIDNEYS

NH3+H+

Glutamine

NH4+

NH3

Glutamic acid

MAINTAINING OF ACIDIC-BASE BALANCE BY KIDNEYS

BloodCells of

canaliculus Cavity of canaliculus

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

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

1,25-dihydroxycholecalciferol

PROPERTIES OF URINE

Amount – 1500-2000 mL/dayPoliuria – diabetes mellitus and insipidusOliguria – heart failure, nephritis, vomiting, feverAnuria – kidney failure, acute intoxication by heavy metals

Color – straw-yellowPale – poliuria (diabetes insipidud)Dark – jaundice, concentrated urineRed – blood availableGreen-blue – decay of proteins in the intestine

Transparency – transparentCloudy – pus or mucin available

Density – 1,003-1,035 g/mLIncreased density – organic or inorganic substances available (diabetes mellitus)Decreased density – diabetes insipidusIsostenuria – continuously low density in oliguria (kidney failure)

pH – 5.5-6.8Acidic – meat food, diabetes mellitus, starvation, feverAlkaline – plant food, cystitis, pyelitis

PATHOLOGICAL COMPONENTS IN URINEHematuria

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

PATHOLOGICAL COMPONENTS IN URINEProteinuria

TypePathophysio-logic features

Cause

GlomerularIncreased

glomerular capillary permeability to

protein

Primary or secondary

glomerulopathy

TubularDecreased tubular

reabsorption of proteins in

glomerular filtrate

Tubular or interstitial

disease

Overflow

Increased production of low-molecular-weight

proteins

Monoclonal gammopathy,

leukemia

DehydrationEmotional stress

FeverHeat injury

Inflammatory processIntense activity

Most acute illnessesOrthostatic (postural)

disorder

COMMON CAUSES OF BENIGN PROTEINURIA

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 URINEGlycosuria

Condition where there is pus or too many white blood cells in the urine

PATHOLOGICAL COMPONENTS IN URINEPyuria

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)

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 URINEBilirubinuria

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 URINEUrobilinuria

Urobilinuria – appearance of urobilin in urine

Brown color of urine- urobilinuria

PATHOLOGICAL COMPONENTS IN URINEPhenylketonuria

Appearance of phenylpyruvate in urine

Phenylketonuria - genetically determined disease which is caused by an absence or deficiency of phenylalanine hydroxylase

FeCl3 test