KIDNEYS

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.

The organs involved in regulation of external

acid-base balance are - blood buffer system,
lungs and kidneys.
Most rapidly react to changes in pH of blood buffer system
within 0.5 - 1 min.
Lungs affect the normalization of pH in 1 - 3 minutes.
A normalizing effect on the kidneys pH change in 10 - 20
hours.
 MAINTAINING OF ACIDIC-BASE BALANCE
Conversion of two substituted phosphates into one
substituted in the cavity of canaliculi;
Cells of
Blood canaliculus Cavity of canaliculus

Na2HPO4

Na+ Na+ Na+ Na+

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

Na+ Na+ Na+

- 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

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

 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 Angiotensin
ІІ
Reabsorption of Na
and water Vasocostriction
The increase of blood volume
The increase of blood pressure
 HORMONAL ACTIVITY (ERYTHROPOIETIN)

Normal level of oxygen in blood The increased

consumption of
oxygen or
decreased amount
of erythrocytes

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.

About 120 mL/min

or 180 L/day of
blood is filtrated.

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

Hydrostatic pressure in glomeruli

is determined by the ratio
between diameter of ascendant
and descendant arteriole
 Reabsorption
Takes place in proximal and distal canaliculi.
Reabsorption - is the process by which
the nephron removes water and solutes from the tubular
fluid and returns them to the circulating blood.

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

Active reabsorbtion - glucose Small reabsorbed - urea

and proteins (100%), amino
and uric acid.
acids (93%),
water – 96%, NaCl (70%) etc.

Not reabsorbed - creatinin, manitol - (sugar alcohol) and

inulin - (polimer of fructose).
 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
•After secretion primary
urine convert into secondary
urine
 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

On kidney affected by some hormones:
Corticoide adrenal male sex hormone and thyroxine
inhibit the reabsorption of water, thereby increasing urine
output.
Parathyroid hormone and antidiuretic hormone
(vasopressin), reduce the secretion of urine by increasing the
absorbability of water. Vasopressin regulated by the nervous
system depending on the amount of liquid in the blood with the
help of osmoregulation reflex. The excess hormone is excreted
in the urine.
Adrenaline in small quantities narrows the excretory vessels
of the kidney, raising the pressure in the nephrons. And in large
doses can lead to the cessation of urine due to the narrowing of
the arteries leading.
 PROPERTIES OF
URINE
Urine is a liquid produced by
the kidneys to remove
waste products from the
bloodstream. Physical
characteristics that can be
applied to urine include
color, turbidity
(transparency), smell
(odor), pH (acidity -
alkalinity) and density.
Color: Typically yellow-
amber, but varies according
to recent diet and the
concentration of the urine.
 Diuresis in healthy people is 1000 - 2000 ml per
day. The daily amount of urine is below 500 ml and
2000 ml higher in adult considered pathological. Man
diuresis - 1500 - 2000 ml in women - 1000 - 1600 ml.
Poliuria – passage of more than 3 L urine
per day - diabetes mellitus and diabetes
insipidus;
Oliguria – less than 400 mL or 500 mL per
24h in adults - heart failure, nephritis,
vomiting, fever;
Anuria – is clinically defined as less than 100
mL urine output per day - kidney failure,
stress, acute intoxication by heavy
metals.
The usual color of urine is straw-yellow. Abnormally
colored urine may be cloudy, dark, or blood-colored. Urine
gets its yellow color from a pigment called urochrome, that
form from urobilin. That color normally varies from pale
yellow to deep amber, depending on the concentration of
the urine.

Cloudy or milky urine is a sign of a urinary tract infection,

which may also cause a bad smell. Milky urine may also be
caused by bacteria, crystals, fat, white or red blood cells, or
mucus in the urine.
Dark brown but clear urine is a sign of a liver disorder such
as acute viral hepatitis or cirrhosis, which causes excess
bilirubin in the urine, jaundice, concentrated urine.
Pink, red or lighter brown urine can be caused
by: beets, blackberries, or certain food colorings.
Hemolytic anemia Injury to the kidneys or urinary
tract, medication. Porphyria, urinary tract
disorders that cause bleeding, blood available.
Dark yellow or orange urine can be caused by:
B complex vitamins or carotene. Medications
such as phenazopyridine (used to treat urinary
tract infections), rifampin, and warfarin Recent
laxative use.
Green or blue urine is due to: artificial colors in
foods or drugs. Bilirubin Medications, including
methylene blue, urinary tract infections, decay of
proteins in the intestine.
 Normal urine is transparent or clear; becomes
cloudy upon standing. Cloudy urine may be
evidence of phosphates, urates, mucus, bacteria,
epithelial cells, or leukocytes.
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
 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

•Trauma of kidneys and

organs of urinary tracts

•Tumors of kidneys and

organs of urinary tracts –
cancer of kidneys,
bladder
 PATHOLOGICAL COMPONENTS OF URINE
Proteinuria
Pathophysio- Cause COMMON CAUSES OF
BENIGN PROTEINURIA
Type logic features Dehydration
Emotional stress
Increased Primary or Fever
Glomerular glomerular capillary secondary Heat injury
permeability to glomerulopathy Inflammatory process
protein Intense activity
Most acute illnesses
Decreased tubular Tubular or Orthostatic (postural)
Tubular reabsorption of interstitial disorder
proteins in disease
glomerular filtrate

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

Is the result of direct

(conjugated) bilirubin in
blood

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