Illustrations are from Robbins Pathologic basis of disease. V.

Kumar,
A.K. Abbas, S.N. Fausto, 7th , 8th , 9th edition, 2007, 2010, 2013;
Harrison’s Principles of internal medicine; Stephen J. McPhee
Pathophysiology of Disease and internet resources. Frolov V.A
Porth Carol, Gaspard Kathryn J. Essentials of Pathophysiology 1
 Purpose of the lecture: to study the main notions
of kidneys pathophysiology
Plan of the lecture
1. Increase and decrease in glomerular filtration, causes,
pathogenesis, consequences.
2. Renal glomerular function disorders, causes,
pathogenesis.
3. Renal tubule function disorders, causes, pathogenesis.
4. Quantitative and qualitative changes of urine .
5. Changes of relative density of urine (specific gravity)
6. Nephrotic syndrome, pathogenesis
7. Nephritic syndrome. Etiology and pathogenesis of
acute glomerulonephritis/
8. Etiology and pathogenesis of pyelonephritis
9. Acute and chronic renal failure, etiology, pathogenesis
10. Uremia, concept, the causes, pathogenesis of
organism’s disorders
 The main functions of kidneys

EXCRETION OF REGULATION OF
WASTE PRODUCTS ELECTROLYTE BALANCE

REGULATION OF
REGULATION OF WATER BALANCE
BLOOD PRESSURE

REGULATION OF ABB
REGULATION OF HEMOPOIESIS

CONTROL OF NITROGEN BALANCE

 Glomerular function impairment

Pathogenesis of glomerular
damage
The basic mechanism is immune
 1. Damage to glomeruli by immune
complexes.

Antigenes are not of glomerular origin

 endogenous (SLE),
 exogenous - bacterial (streptococci), viral
(hepatitis B), parasitic (Plasmodium
falciparum malaria), and spirochetal
(Treponema pallidum) infections.
 Immune complexes are formed in circulation then
captured by glomeruli
Localization is depend on:
 Renal hemodynamics,
mesangial cells
function, charge of
basement membrane
 The charge and size of
particles
• Large positively charged
particles cross
basement membrane
and localize
subepithelially (acute
glomerulonephritis)
• Negativly charged
particles cannot
cross basement
membrane and
localize
subendothelially
(SLE, membrano
proliferative
glomerulonephritis)
• Neutral charged
particles are localized
within mesangium
• Localization of
complexes within
basement membrane
gives membranous
nephropathy
• Large complexes are
phagocytosed by
macrophages
Antigen-antibody complexes deposited in
the glomeruli elicit a local inflammatory reaction
that produces injury.

• engagement of Fc receptors on leukocytes,

glomerular mesangial or other cells
• Activation of complement system

The glo­merular lesions may exhibit leukocytic

infiltration and proliferation of mesangial and
endothelial cells.
2. In Situ Formation of Immune Complexes

• Antibodies Against Planted Antigens

Immune complexes are formed
locally by antibodies that react with intrinsic
tissue antigen or with extrinsic antigens
"planted" in the glomerulus from the circulation
(cationic molecules, DNA, bacterial products,
nuclear proteins, the aggregated large proteins,
immune complexes themselves, since they
continue to have reactive sites for further
interactions with free anti­body, free antigen, or
complement.
• .
2. In Situ Formation of Immune Complexes

• Antibodies Directed Against Normal

Components of the Glomerular Basement
Membrane

Antigens are normal components of the

Glomerular Basement Membrane.
Anti­bodies bind to intrinsic
antigens homogeneously distrib­
uted along the entire length of the
GBM, resulting in a diffuse linear
pattern of staining for the
antibodies by immunofluorescence
techniques.

Anti-GBM antibodies may cross-

react with basement membranes of
lung alveoli, resulting in
simultaneous
lung and kidney lesions
(Goodpasture syndrome).
3. Cell - mediated mechanism (type IV)
Damage by sensitized Т-lymphocytes
Sensitized T cells cause glomerular
injury and are involved in the
progression of some
glomerulonephritides.
 Cellular
Macrophages, sensitized Т-lymphocytes,
NK cells, neutrophils, platelets, resident
glomerular cells (epithelial, mesangial,
endothelial)

arachidonic acid metabolites, NO,

angiotensin, endothelin

Hemodynamic disorders
 proteases, ROSs alteration
 Cytokines (IL-1, TNF) local and
systemic responce
 Chemokines leukocyte emigration
tissue infiltration
 Growth factors: PDGF mesangial cell
proliferation; TGF, connective tissue growth
factor, and fibroblast growth factor
ECM deposition and hialinization leading to
glomerulosclerosis in chronic injury.
VEGF maintain endothelial integrity and may
help regulate capillary permeability.
•
 Humoral
Complement system

Phagocytosis activation, formation of MAC

C5b-C9

Destruction of cells, activation of mesangial

cells, leukocytes
• Clotting system

• Fibrinogen (procoagulants activity of

macrophages fibrin formation within
the Boumen’s space stimulation of
endothelial cells proliferation (formation of
crescent-shaped mass).
• Inhibitor of plasminogen activator
thrombi formation, fibrosis
 Clearance tests determine
the quantity of glomerular filtrate formed
each minute in all nephrons of both kidneys
- glomerular filtration rate (GFR)
Clearance – is the volume of plasma cleared
from any substance per minute
C = (U/P) x V
С – clearance; U - concentration of the test -
substance in urine
P - concentration of the test - substance in
plasma; V - minute diuresis
GFR at the healthy person is 80 - 120 ml / min
(clearance of endogenous creatinine)
The filtration occurs under the influence
of Effective filtration pressure
EFP = HP - (OP+ CP)
HP - hydrostatic
pressure of
blood in glomerular
capillaries
OP - oncotic pressure of
blood in glomerular
capillaries
CP - hydrostatic
pressure of ultrafiltrate
in Bowman’s space
 Reduction in glomerular filtration

а) Decreased effective filtration pressure

 Decreased hydrostatic pressure in
glomerular capilaries (hypotension, systolic
pressure less than 80 mm Hg, renal
ischemia, etc.)
 Increased blood oncotic pressure
 Increased intracapsule hydrostatic pressure
(difficulty of urine outflow)
Decrease in glomerular filtration

Decrease in diuresis
 Increase in glomerular filtration
а) Increased effective
filtration pressure
Increased hydrostatic
pressure in glomerular
capillaries
increased glomerular
efferent arterioles tone
(catecholamines,
angiotensin,
vasopressin)
Decreased glomerular afferent arterioles tone
(kinins, prostaglandins A, E)
Decreased oncotic pressure in glomerular
capillaries
b) Increase in permeability of the filtering
membrane
Increased glomerular filtration

Increased diuresis
 Tubulopathy
Hereditary Acquired

Hereditary tubulopathy
Inherited renal phosphate diabetes
reduced phosphate reabsorption

phosphaturia, hypophosphatemia
calciuria

rachitis, osteomalacia
• Hyperaminoaciduria (cystinuria)

• Syndrome de Toni – Debre –

Fanconi: the main pathogenetic
factor —enzymatic defect in
Krebs cycle of mitochond.
• Impaired reabsorption of glucose,
phosphates, bicarbonates, amino
acids, proximal tubular acidosis
(loss of hydrocarbonates)

• Renal water diabetes (lack of

response to ADH)
• Pseudohypoaldosteronism
 Acquired tybulopathy
• Damage of tubular epithelium (toxins, hypoxia,
obturation by casts (cylinders), hemoglobin,
myoglobin)
• Decreased activity of transport proteins
(participating in reabsorption and secretion)
• Decreased energy supply of tubular
transmembrane transport processes
• Overload of reabsorption processes (more than
renal threshold)
• Disorders of hormonal regulation of
reabsorption processes (aldosterone,
vasopressin, atrial peptide)
• Mechanisms of chronic tubulointerstitial injury in
glomerulonephritis Various components of the protein-rich
filtrate and cytokines derived from leukocytes cause tubular cell
activation and secretion of cytokines, growth factors, and other
mediators. These, together with products of macrophages, incite
interstitial inflammation and fibrosis. ET-1, endothelin-1, PAI-1,
plasminogen activator inhibitor-1; TIMP-1, tissue inhibitor of
metalloproteinases.
 Proximal convoluted tubule damage
• Reduced
reabsorption of
glucose,
aminoacids,
albumins, urea,
lactic acid,
bicarbonates,
phosphates,
chlorides,
potassium, etc.
• Proximal tubular
acidosis
 Distal convoluted tubule damage
• reduced
reabsorption of
Na+, K+, Mg+,
Ca+, H2O
• distal tubular
acidosis
*Manifestations of excretory function disorders

signs
Urine syndrome
Diuresis hematuria
abnormalities

leukocyturia

cylinderuria

proteinuria crystalluria

13
 Quantitative changes of diuresis
Diuresis – is urine excretion within 24 hours

• Polyuria more than 2 L

• Oliguria less than 0.5 L
• Anuria less than 50 (100) mL
 POLYURIA
Is increase in diuresis
(more than 2 liters)
Pathogenesis
• increased glomerular filtration
• reduction in glomerular reabsorption
(water or osmotic diuresis)

Types of polyuria according to origin

Prerenal Renal
 Prerenal polyuria
а Physiological (after reception of
plenties of water)

b) Pathological
 initial stage of arterial hypertension
(vasoconstriction of efferent arterioles)
 hypervolemia
 endocrinopathy (diabetes mellitus,
diabetes insipidus)
 Renal polyuria
Renal failure (increased permeability of the
filtering membrane, impairment of renal
countercurrent multiplier system
functioning )
 OLIGURIA
is reduction in daily diuresis less than
500ml
ANURIA - (absence of urine)
Absence of urine formation and
urination (diuresis is less than 50 ml)
PATHOGENESIS
 reduction of glomerular filtration
 increased tubular reabsorption of sodium
and water
 mechanical obstruction for urine passage
 Types of oliguria and anuria
according to origin
Prerenal
Renal
Postrenal
 Prerenal oligo-anuria
THE REASONS
 reduction of the systolic arterial
pressure less than 80 mm Hg.
hypovolemia
increase in blood oncotic pressure
(transfusions of great volumes of
albumin solutions)
Postrenal oligo-anuria
Causes

diminished urine
outflow through
urinary passways

increase in glomerular
capsule pressure

reduction of filtration
process
• Pollakiuria – is frequent urination (at
cystitis, prostate adenoma)
• Nocturia is predominant night diuresis
(at renal diseases and heart failure)
 QUALITATIVE CHANGES OF URINE

Proteinuria – is protein in urine

Under normal conditions there are
traces of protein in urine (150 mg per
24 hours):
60 % albumins, 40 % uroprotein
(Tamm Horsefall protein)
 Types of proteinuria according to
significance for organism

Physiological Pathological
(functional) (at pathological
(for healthy kidneys, processes)
proteinuria is less
than 1 g/day)
 orthostatic
 at heavy physical
work
Types of proteinuria according to
pathogenesis

Glomerular
Tubular
 Glomerular proteinuria

Pathogenesis: increased permeability of

glomerular filtering membrane

marked excretion of plasma proteins (from

4.0 – 5.0 g up to 50 g per 24 hours)
(the greatest proteinuria is observed at
nephrotic syndrome:
 Types of proteinuria according to
appearance of different proteins in urine
Selective Not selective
is observed at Increase in
nephrotic syndrome permeability of
(minimal change glomerular filter
disease) loss of albumins,
a negative charge of transferrin +
glomerular filter
albumins and high molecular
transferrin in urine proteins (IgG) in
(more than 90 %
urine
children of 1- 6 years)
 HEMATURIA

Renal Extrarenal

Renal
increased glomerular capillaries
permeability

appearance of changed, dysmorphic

(glomerular) erythrocytes in urine
(irregular shape, size, and cell membrane)
lEUKOCYTURIA – leukocytes in urine
(urinalysis –6-8 /HPF)
PYURIA is pus in urine
Is large number of leukocytes in urine
More than 200 /HPF

Shtergeimer- Malbin Cells - Active alive segmented

neutrophils, increased in size with pale-blue, segmented
nuclei, uncolored cytoplasm, they appear in acute
inflammation
Urocytograms:
neutrophils— infection, pyelonephritis, tbc
mononuclears — glomerulonephritis, interstitial nephritis
lymphocytes— SLE, rheumatoid arthritis
Eosinophils — allergy
 Changes of specific gravity of urine
• Specific gravity of urine reflects renal
concentrating ability
• It is proportional to concentration of the
dissolved substances (urea, uric acid, salts,
creatinine and other organic and nonorganic
products)
• It is provided by the work of countercurrent
mechanism
• Under usual conditions it is 1.018 – 1.025
• Changes in specific gravity are due to
decreased renal tubules functional capacity.
 Hyposthenuria
is decreased specific gravity of
urine less than 1.010 in all portions
of Zimnitzky’s test

Hypersthenuria
is increased specific gravity of urine
(is observed at diabetes mellitus)
 Isosthenuria
is constant specific gravity and equal
the specific gravity of the primary
urine (ultrafiltrate) – 1.010- 1.012.
Isosthenuria reflects the failure of
renal concentration ability.
 The main syndromes
at renal diseases
Nephritic syndrome
is caused by Glomerular disease and is
dominated by the acute onset of either grossly
visible hematuria or microscopic hematuria
with dysmorphic red cells and red cell casts on
urinalysis, diminished GFR, mild to moderate
proteinuria, and hypertension.
It is the classic presentation of acute
poststreptococcal glomerulonephritis.
Rapidly progressive glomerulonephritis is
characterized as a nephritic syndrome with
rapid decline in GFR (within hours to days).
 Glomerulonephritis
Is the Group of diseases characterized by
inflammation of the glomeruli
Classification according to Pathogenesis
• Immune complex mediated glomerulonephritis
• Glomerulonephritis caused by formation of
antibodies to antigens in the basal membrane of
glomeruli
According to duration
• Asymptomatic hematuria (immunoglobulin-A -
nephropathy, or focal segmental
glomerulonephritis )
• Acute glomerulonephritis
• Rapidly progressive glomerulonephritis
• Chronic glomerulonephritis
 Poststreptococcal Glomerulonephritis
• It usually appears 1 to 2 (4) weeks after a
streptococcal infection of the pharynx or
skin (impetigo)
• Cause: certain strains of β-hemolytic
streptococci: group A, types 12, 4, 1
• Blood analysis reveals antibodies to
antigens of streptococci: antistreptolysin
ASO, anti-DNA-ase, antihyaluronidase;
reduced levels of C3
• Poststreptococcal GN is caused by immune
complexes containing streptococcal antigens
and specific antibodies, which are formed in
situ.
• The antigens are planted from the circulation
in subendothelial locations in glomerular
• capillary walls, leading to in situ formation of
immune complexes, where they elicit an
inflammatory response. Then they
dissociate, migrate across the GBM, and re-
form on the subepithelial side of the GBM.
Manifestations
In the typical case, a young child abruptly
develops malaise, fever, nausea, oliguria, and
hematuria (smoky or cola-colored urine, the
color of meat slops) 1 to 2 weeks after
recovery from a sore throat.
The patients have dysmorphic red cells
or red cell casts in the urine, mild proteinuria
(usually less than 1 -3 gm/day), periorbital
edema, and mild to moderate hypertension.
Most affected children recover; the prognosis
is worse in adults.
 Rapidly Progressive (Crescentic)
Glomerulonephritis

• is associated with severe glomerular injury

with necrosis and GBM breaks and
subsequent proliferation of parietal epithelial
cells (forming crescents) due to damage by
• autoantibodies against the GBM or by
immune complexes
• Circulating antibodies against neutrophil
cytoplasmic antigens
• Bowman’s space is filled with fibrin, proliferating parietal
epithelial cells, monocytes and macrophages (Crescents).
The crescents may obliterate the urinary space and
compress the glomerular tuft.
It is characterized by rapid and progressive loss of
renal function associated with severe oliguria and signs of
nephritic syndrome; if untreated, death from renal failure
occurs within weeks to months.
 Nephritic syndrome
 Proteinuria less
than 1-3 g/day
 Hematuria (color
of meat slops),
erythrocyte casts
 Hypertension
 Edema
 Decreased GFR
 Hematuria, RBC • permeability of
casts
filtering membrane
 Proteinuria less
than 1- 3 g/day
 Hypertension
• Hypervolemia
• Activation of RAAS
• Decreased production
of depressive
substances
 Azotemia • GFR
 Nephritis
number of Generalized
functioning vasculitis
nephrons
renal blood supply

permeability of
GFR Activation vessels
of RAAS

Hypervolemia Proteinuria
oncotic ressure
EDEMA
 Nephrotic syndrome
is caused by a derangement in
glomerular capillary walls
resulting in increased
permeability to plasma proteins
and manifested by:
• Massive proteinuria, with the
daily loss of 3.5 gm or more
of protein (less in children)
• Hypoalbuminemia, with plasma
albumin levels less than
3 gm/dL
• Generalized edema
• Hyperlipidemia and lipiduria
The nephrotic syndrome is caused by
 minimal-change disease (for children) Primary
 membranous glomerulopathy, and
focal segmental glomerulosclerosis.
(for adults)

 Diabetic nephropathy
 amyloidosis
Secondary
 SLE
• Minimal-Change Disease is characterized
by diffuse effacement of foot processes
of visceral epithelial cells (podocytes),
detectable only by electron microscopy.
Antibodies to podocyte
antigens, toxins, cytokines,
or other factors foot
process effacement and
variable degrees of
podocyte detachment

Loss of negative charge by the basement

membrane increased permeability for
plasma proteins
Membranous nephropathy
is a form of chronic
immune complex-mediated
disease.
C5b-C9 activates
glomerular epithelial and
mesangial cells
liberation proteases and
oxidants capillary wall
injury and increase in
protein leakage.
 Manifestation Pathogenesis
Proteinuria (usually Loss of negative charge by
selective) basement membrane,
gamage to podocytes at
minimal change disease
Hypoproteinemia
 Increased permeability
under the influence of BAS,
Гипоонкия, lysosomal enzymes, ROSs
at membranous
edema glomerulonephritis
 Blood oncotic pressure
Shifting of fluid into tissues
Hypovolemia
Dcreased renal blood supply
Activation of RAAS GFR
Na reabsorption

ADH secretion

water reabsorption

interstitial fluid,
edema
• Hyperlipidemia: • hepatic lipoprotein
• LDL, VLDL synthesis
• cholesterol and • catabolism of
TAG chylomicrones and
VLDL (loss of
lipoproteinlypase with
urine)
• Vit D, Zn, CU, Fe
• Loss of transport
deficiency
proteins with urine
 Thrombotic and fibrinogen, V, VIIIf
thromboembolic antithrombin III,
complications plasminogen,
antiplasmin activity
platelets count and their
adhesiveness
Infectious
complications Loss of IgA, IgG in the
urine
Hypocalciemia

Hyperparathyroidism Loss of Ca and vit. D

metabolites in urine
osteoporosis
 Changes in urine:
 oliguria
 high specific gravity of urine
 massive proteinuria
 lipiduria
 Hyaline, lipid, epithelial casts, oval fat
bodies
 glycosuria, aminoaciduria, phosphaturia,
tubular acidosis (damage to tubules by
proteinuria)
 Chronic glomerulonephritis
• Chronic glomerulonephritis refers to end-stage glomeru­
lar disease that may result from specific types of glomeru­
lonephritis or may develop without antecedent history of
any forms of acute glomer­ulonephritis.
• A slowly progressing inflammation of the glomeruli,
culminating in the replacement by fibrous tissue and
development of chronic renal failure
 Pyelonephritis
Pyelonephritis is one of the most common
diseases of the kidney and is defined as
inflammation affecting the tubules,
interstitium, and renal pelvis.
Causes:
More than 85% of cases of urinary tract
infection are caused by the gram-negative
bacilli that are normal inhabitants of the
intestinal tract: Escherichia coli, Proteus,
Klebsiella, Enterobacter, Streptococcus
faecalis
Routes by which
bacteria can reach the
kidneys:
(1) hematogenous
(2) from the lower
urinary tract
(ascending
infection)
 Conditions for the development of pyelonephritis

• Urinary obstruction, either congenital or acquired

• Instrumentation of the urinary tract, most commonly
catheterization
• Vesicoureteral reflux
• Pregnancy—4% to 6% of pregnant women develop bac-
teriuria during pregnancy
• Female gender and patient age. Infections are much more
frequent in females. With increasing age, the incidence
in males rises (development of prostatic hyperplasia
• Preexisting renal lesions, causing intrarenal scarring and
obstruction
• Diabetes mellitus (infection and bladder dysfunction)
• Immunosuppression and immunodeficiency
 Pathogenesis of pyelonephritis
1. Colonization of the distal urethra by coliform
bacteria.
P-fimbriae (pili) of bacteria interact with
receptors on the surface of urothelial cells.
Specific adhesins are associated with infection.
In addition, certain types of fimbriae promote
renal tropism, persistence of infection, or an
enhanced inflammatory response.
From the urethra to the bladder
• Prostatic fluid has antibacterial properties so
organisms gain entrance during urethral
catheterization or other instrumentation.
• Urinary infections are much more common in
females (urethra in females is shorter, hormonal
changes influence adherence of bacteria to the
urethral mucosal epithelium)
3.Bacteria in the
bladder
Bladder urine has
antimicrobial properties
Reproduction of microbes
is increased in case of
• outflow obstruction
• bladder dysfunction
• Disorders of innervation
• Compression of uretra,
• Hypertrophy of prostate
4. Vesicoureteral reflux
incompetent vesicoureteral valve
(inherited disorders or shortening of the
cystic portion of the ureter, persistent
bladder atony caused by spinal cord
injury.).
5. Intrarenal reflux.
is most common in the
upper and lower poles
of the kidney, where
papillae tend to have
flattened or concave
tips
 Acute pyelonephritis, a common suppurative
inflammation of the kidney and the renal
pelvis.
 The hallmarks of acute pyelonephritis are
patchy interstitial suppurative inflammation,
intratubular aggregates of neutrophils,
neutrophilic tubulitis and tubular necrosis
Manifestations
Sudden onset of pain at the costovertebral angle and
systemic evi­dence of infection (fever leukocytosis
with shift to the left, increased ESR)
 Dysuria, frequency, and urgency (indications of
bladder and urethral irritation)
The urine contains many leukocytes (pyuria) derived
from the inflammatory infil­trate. The finding of
leukocyte casts, typically rich in neutrophils (pus
casts), indicates renal involvement
The diagnosis of infection is established by
quantitative urine culture.
Uncomplicated acute pyelonephritis follows a benign
course, and symptoms disappear within a few days
after the institution of appropriate antibiotic therapy
Chronic pyelonephritis is a disorder in
which chronic tubulointerstitial
inflammation and scarring involve the
calyces and pelvis. It is an important cause
of chronic renal failure.
 Renal failure

Acute Chronic

Acute renal failure

is rapid decline in renal functions
 Chronic renal failure- chronic kidney
disease
is progressive and irreversible deterioration of
renal function due to slow destruction of renal
parenchyma, eventually terminating in death
when sufficient number of nephrons have been
damaged. It is the end result of all chronic
renal parenchymal diseases
 The reasons:
Chronic diseases of kidneys and urinary
tract: glomerulonephritis, pyelonephritis
polycystic kidney disease, urolithiasis,
hydronephrosis, diabetic nephropathy,
damage of kidneys at essential
hypertension, atherosclerosis
 PATHOGENESIS

• Progressive destruction of
nephrons and their replacement by
connective tissue
(nephrosclerosis) progressing
reduction of tubular and
glomerular functions reduction of
urine formation uremia
uremic coma
 Stages of chronic renal failure

1. Latent
(diminished renal reserve)
Glomerular filtration rate is reduced up to
50 %, blood urea nitrogen (BUN) and
creatine values are normal. The patients
are usually asymptomatic except at times
of stress or in concentration tests.
Pathogenesis of progression
of renal insuffisiency
 Compensatory hypertrophy of undamaged
nephrones

Hyperfiltration and increase in intracapillary

pressure

Damage of endothelium and epithelium,

increased permeability for proteins

Proliferation of mesangial cells, macrophagal

infiltration (cytokines)

Interstitial fibrosis, nephrosclerosis and uremia

 2. Hyperazotemic stage (Azotemic phase,
renal insufficiency).
About 75% of functional renal parenchyma
has been destroyed. The GFR is about 25%
of normal accompanied by elevation in BUN
and serum creatinine. Polyuria and nocturia
occur due to tubulointestinal damage
3. Uremic stage (renal failure)
 About 90% of functional renal tissue has been
destroyed . The GFR is approximately 10% of
normal. Tubular cells are not functional.
 End-stage kidneys (4). The GFR is less than 5%
of normal and results in complex clinical picture
of uremia
• In diminished renal reserve, the GFR is about 50% of
normal. Serum BUN and creatinine values are normal,
and the patients are asymptomatic. However, they are
more susceptible to developing azotemia with an
additional renal insult.
2. In renal insufficiency, the GFR is 20% to 50% of
normal. Azotemia appears, usually associated with
anemia and hypertension. Polyuria and nocturia can
occur as a result of decreased concentrating ability.
Sudden stress (e.g., with nephrotoxins) may
precipitate uremia.
3. In renal failure, the GFR is less than 20% to 25%
of normal. The kidneys cannot regulate volume and
solute composition, and patients develop edema,
metabolic acidosis, and hypocalcemia. Overt uremia
may ensue, with neurologic, gastrointestinal, and
cardiovascular complications.
4. In end-stage renal disease, the GFR is less than
5% of normal; this is the terminal stage of uremia.
 Stages of chronic renal failure
according to diuresis changes

1. Latent
Diuresis is normal, Zimnizky’s test is
normal, concentration test shows
decreased renal reserve (the concentration
of the urea will remain constant regardless
of stress of water deprivation)
 2. Polyuria (diuretic stage)
Reduction in concentration function of
tubules. There is decreased
concentration of urine without
overload, hypostenuria, fixed specific
gravity of urine (isosthenuria)
 Pathogenesis of poliuria:

 Hyperfiltration of healthy nephrones

decreased the time of ultrafiltrate
contact with tubular epithelium
decreased reabsorption of electrolytes
osmotic diuresis

 Decreased of interstitium osmolality

disturbances of countercurrent
mechanism work
 3. Oliguric phase.
Diuresis is less than 500 ml,
isosthenuria, uremic syndrome
 UREMIA (uremic syndrome)
(from Greek. Uron- urine, haima -
blood) – urine in blood

End-stage kidney, ESRD

Syndrome of decompensated
renal failure
 PATHOGENESIS

1. Autointoxication byuremic toxins

(waste-products of protein
metabolism, normally excreted by
kidneys:urea, uric acid, creatine,
creatinine, ammonia; phenols, indole,
oligopeptides
 Parathyrin

Increase in intracellular
calcium

Decrease in oxidative phosphorilation

Disfunction of the heart, osteodystrophy,

neuropathy

. Metabolic disorders (STH, insulin,

glucagon, prolactin)
2. Water and electrolyte imbalance
 hypoosmolar hyperhydration
 hyperkalemia (since K+ is normally excreted
mainly in the urine). Hyperkalemia is further
worsened by metabolic acidosis. The clinical
features of hyperkalemia are: cardiac
arrhythmias, weakness, nausea, intestinal
colic, diarrhea, muscular irritability and
paralysis
 Hypermagnesemia  encephalopathy
 Hypocalcemia  renal osteodystrophy
 Increased phosphates, sulphates
3. Metabolic acidosis (decreased reabsorbtion of
bicarbonates, decreased secretion of hydrogen
ions)  Kussmaul breathing, electrolyte
disorders
4. Disorders of hormone and vitamin metabolism
(vit .D)
5. Impaired production of erythropoietins,
prostaglandins, kinins, etc.
 Extra-renal manifestations

1. Neurological symptoms
fatiguability, headache, low reflexes,
impaired taste, sleepness,
depression, edema, coma
2. Cardiovascular system disorders
• heart failure due to hypervolemia, cell
dystrophy, cardiac arrhythmias,
pericarditis, hypertension
 HYPERTENSION
activation of renin-angiotensin-aldosterone
system, decreased formation of depressive
substances

Renin
Angiotensinogen
Angiotensin I II
Aldosterone
 3. Respiratory system
uremic pneumonitis, pulmonary edema,
pleuritis

4. Blood
• anemia (decresed production of
erythropoietin, hemolysis)
• hemorrhagic syndrome
• DIC-syndrome