24. Clinical biochemistry of kidneys

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KIDNEYS
CLINICAL
BIOCHEMISTRY
Two layers:
medulla.
external
–
cortex,
inner
–
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 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
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 mL/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%), NaCl (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 pH.
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 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-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
НСО3- ammonia excretion
MAINTAINING OF ACIDIC-BASE BALANCE BY
KIDNEYS
Blood
Cells of
canaliculus
Cavity of canaliculus
Na2HPO4
Na+
Na+
Na+
Na+
HPO42-
H+
H+
NaH2PO4
MAINTAINING OF ACIDIC-BASE BALANCE BY
KIDNEYS
Blood
Cells of
canaliculus
Cavity of canaliculus
NaHCO3
Na+
Na+
HCO3
-
H+
Na+
H+ HCO3-
H2CO3
H2CO3
H2O + CO2
H2O
CO2
MAINTAINING OF ACIDIC-BASE BALANCE BY
KIDNEYS
Blood
Cells of
canaliculus
Cavity of canaliculus
Glutamine
NH3
NH3+H+
Glutamic acid
NH4+
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 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
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
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
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
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
FeCl3 test
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