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BIOCHEMISTRY
Kidney – the couple organ, which is responsible for excretion
of final products of metabolism and for maintains homeostases.
Two layers: external – cortex, inner – medulla.
Functional-
structural unit
of kidney –
nephron.
Every kidney
contain –
about
1.000.000
nephrons.
KIDNEY FUNCTIONS
- Excretion of the end products (metabolites, drugs,
toxins);
- Urine formation;
- Homeostatic function:
- 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)
- Metabolism of proteins, lipids, carbohydrates,
energetic metabolism
MAINTAINING OF ACIDIC-BASE BALANCE
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.
Na2HPO4
HPO42-
H+ H+
NaH2PO4
MAINTAINING OF ACIDIC-BASE BALANCE
Formation of carbonic acid in the cells with the
following dissociation to Н+ and НСО3-;
Cells of
Blood canaliculus Cavity of canaliculus
NaHCO3
- H+ H+ HCO3-
HCO3
H2CO3
H2CO3
H2O + CO2
H2O CO2
MAINTAINING OF ACIDIC-BASE BALANCE BY
ammonia excretion.
Cells of
Blood canaliculus Cavity of canaliculus
Glutamine
NH3 NH3+H+
Glutamic acid
NH4+
REGULATION OF BLOOD PRESUURE BY KIDNEYS
REGULATION OF BLOOD PRESSURE BY KIDNEYS
The decrease of blood pressure, hypovolemia
Reaction of volume-receptors
Impulses to hypothalamus
Constriction of arterioles
Rhenin
Angitensinogen Angiotensin І
Angiotensin-converting
enzyme
Secretion of aldosteron Angiotensin
ІІ
Reabsorption of Na
and water Vasocostriction
The increase of blood volume
The increase of blood pressure
HORMONAL ACTIVITY (ERYTHROPOIETIN)
The increase of
oxygen in blood The decrease of
oxygen level in blood
Increased number Formation of
of erythrocytes erythropoietin by
kidneys
Intensified
erythropoiesis Erythropoietin
stimulation
Bone marrow
Erythropoietin (EPO) is a hormone secreting by kidney to increase the
production of red blood cells by the bone marrow. Kidney senses the low-
oxygen level in the blood that reaches it and responding to it by secreting
erythropoietin by a kidney cell.
Erythropoietin is best for low blood pressure treatment, if the cause of low
BP is due to anemia. Erythropoietin can increase RBC (red blood
corpuscles) and thus raises your blood pressure. Erythropoietin as a
medicine stimulates the bone marrow to make red blood cells.
Active form of
vitamin D -
1,25-dihydro-
xycholecalci-
ferol is formed
in kidneys
1,25-dihydroxycholecalciferol
In the kidney active many metabolic processes. Kidney contain
91-96% of water. They use about 10 % of all O2, which used in
organism. During 24 hours through kidney pass 700-900 L of
blood. The main fuel for kidney are carbohydrates. Glycolysis,
ketolysis, aerobic oxidation and phophorillation are very intensive
in kidney. A lot of ATP formed in result.
Utilization of glucose in cortex
and medulla is differ.
Dominative type of glycolysis in
cortex is aerobic way and CO2
formed in result.
In medulla dominative type is
anaerobic and glucose converted
to lactate.
Metabolism of proteins also
present in the kidney in high
level. Especially, transamination
and deamination is very active
and a lot of free ammonia formed.
In kidney take place the first
reaction of creatin synthesis.
Kidney contain plenty of different enzymes:
LDG (1, 2, 3, 5), AsAT, AlAT.
Specific for kidney is alanine amino peptidase (AAP), have
5 isoforms, every isoforms are specific for a particular organs.
AAP1 – main place localisation - liver tissue, AAP2 - in the
pancreas, AAP3 - kidney, AAP4 and the AAP5 - in different
parts of the intestinal wall.
Alanine aminopeptidase is an enzyme that is
used as a biomarker to detect damage to the
kidneys, and that may be used to help
diagnose certain kidney disorders. It is found at
high levels in the urine when there are kidney
problems.
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.
Filtration – passive
process.
In result of filtration
formed primary urine
(urine without
proteins -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
Reabsorption:
active
passive.
Lipophilic substances
- passive.
Na/K АТP-аse is very
active
3 groups of reabsorption
substances :
1. Substances, that actively
reabsorbed
2. Substances, that small
reabsorbed
3. Substances, that not
reabsorbed
pH – 5.5-6.8
Acidic – meat food, diabetes mellitus, starvation,
fever
Alkaline – plant food, cystitis, pyelitis
Smell (odor) of urine
Slightly aromatic, characteristic of freshly voided urine. Urine
becomes more ammonia-like upon standing due to bacterial
activity - urea convert in to ammonia. Ammonia formed very
acute smell.
ABNORMAL CONSTITUENT: ASSOCIATED CAUSES:
Albumin is normally too large to pass through
glomerulus. Indicates abnormal increased
permeability of the glomerulus membrane. Non-
Protein (albumin) – pathological causes are: pregnancy, physical
exertion, increased protein consumption.
Pathological causes are: glomerulonephritis
bacterial toxins, chemical poisons.
Glycosuria is the condition of glucose in urine.
Normally the filtered glucose is reabsorbed by
the renal tubules and returned to the blood by
Glucose – carrier molecules. If blood glucose levels exceed
renal threshold levels, the untransported glucose
will spill over into the urine. Main cause:
diabetes mellitus
ABNORMAL CONSTITUENT: ASSOCIATED CAUSES:
Ketone bodies such as acetoacetic acid,
beta-hydroxybutyric acid, and acetone can
appear in urine in small amounts. These
Ketones –
intermediate by-products are associated
with the breakdown of fat. Causes:
diabetes mellitus, starvation, diarrhea
Bilirubin comes from the breakdown of
hemoglobin in red blood cells. The globin
portion of hemoglobin is split off and the
heme groups of hemoglobin is converted
into the pigment bilirubin. Bilirubin is
secreted in blood and carried to the liver
Bilirubin –
where it is conjugated with glucuronic
acid. Some is secreted in blood and some
is excreted in the bile as bile pigments into
the small intestines. Causes: liver
disorders, cirrhosis, hepatitis, obstruction
of bile duct
ABNORMAL CONSTITUENT: ASSOCIATED CAUSES:
Bile pigment derived from breakdown of
hemoglobin. The majority of this substance is
excreted in the stool, but small amounts are
Urobilinogen –
reabsorbed into the blood from the intestines and
then excreted into the urine. Causes: hemolytic
anemias, liver diseases
Hemoglobinuria is the presence of hemoglobin in
the urine. Causes: hemolytic anemia, blood
Hemoglobin –
transfusion reactions, massive bums, renal
disease
Hematuria is the presence of intact erythrocytes.
Almost always pathological. Causes: kidney
Red blood cells –
stones, tumors, glomerulonephritis, physical
trauma
The presence of leukocytes in urine is referred to
White blood cells – as pyuria (pus in the urine). Causes: urinary tract
infection
Presence of bacteria. Causes: urinary tract
Nitrite –
infection
Vitamins: C (20-30 mg); B1 ().1-0>3 mg); B2 (0,5-0,8 mg).
Hormones: 17-ketosteroids
Human urine consists primarily of water (91% to 96%), organic solutes
including urea, creatinine, uric acid, and trace amounts of enzymes, carbohydrates,
hormones, fatty acids, pigments, and mucins, inorganic ions such as sodium (Na+),
potassium (K+), chloride (Cl-), magnesium (Mg2+), calcium (Ca2+), ammonium
(NH4+), sulfates (SO42-), and phosphates (e.g., PO43-). A representative chemical
composition would be:
water (H2O): 95%
urea (H2NCONH2): 9.3 g/l to 23.3 g/l
chloride (Cl-): 1.87 g/l to 8.4 g/l
sodium (Na+): 1.17 g/l to 4.39 g/l
potassium (K+): 0.750 g/l to 2.61 g/l
creatinine (C4H7N3O): 0.670 g/l to 2.15 g/l
inorganic sulfur (S): 0.163 to 1.80 g/l
.
Lesser amounts of other ions and compounds are present,
including hippuric acid, phosphorus, citric acid,
glucuronic acid, ammonia, uric acid, and many others.
PATHOLOGICAL COMPONENTS OF URINE
Hematuria
Causes of
hematuria Macrohematuria
•Infectious diseases –
glomerulonephrotis,
pyelonephritis, prostatitis,
uretritis, cystitis
Microhematuria
•Stones in kidneys and
urinary tracts
Increased Monoclonal
production of low- gammopathy,
molecular-weight leukemia
Overflow
proteins
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
Noninfectious causes
•treatment with glucocorticoids
•mechanical trauma
•kidney stones
Cloudy urine - pyuria
•tumors (benign or malignant)
PATHOLOGICAL COMPONENTS IN URINE
Bilirubinuria
Bilirubinuria – appearance
of bilirubin in urine
Causes:
•mechanical jaundice
Brown color of urine •parenchimal jaundice
- bilirubinuria
PATHOLOGICAL COMPONENTS IN URINE
Urobilinuria
Urobilinuria – appearance of
urobilin in urine
Causes
•overburdening of the liver
•excessive RBC breakdown
•increased urobilinogen
production
•a large hematoma
•restricted liver function
•hepatic infection
Brown color of urine
- urobilinuria
•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