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KIDNEYS:
CHEMICAL PATHOLOGY
Two layers: external – cortex, inner –
medulla.
Functional-
structural unit
– nephron.
Every kidney
has – about
1,000,000
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
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:
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)
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.
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
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/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
Macrohematuria
Microhematuria
Causes of
hematuria
•Infectious diseases –
glomerulonephritis,
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 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
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
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)
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
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
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
THANKS

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Kidneys CLINICAL biochemistry.ppt111111111

  • 2. Two layers: external – cortex, inner – medulla.
  • 3. Functional- structural unit – nephron. Every kidney has – about 1,000,000 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 D3) -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 НСО3 - - ammonia excretion MAINTAINING OF ACIDIC-BASE BALANCE BY KIDNEYS
  • 17. 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
  • 18. Active form of vitamin D - 1,25-dihydro- xycholecalci- ferol is formed in kidneys 1,25-dihydroxycholecalciferol
  • 19. 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
  • 20. 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
  • 21. PATHOLOGICAL COMPONENTS IN URINE Hematuria Macrohematuria Microhematuria Causes of hematuria •Infectious diseases – glomerulonephritis, 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
  • 22. 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
  • 23. 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
  • 24. 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)
  • 25. 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
  • 26. 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
  • 27. 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