Diseases of the kidneys
1. Glomerulopathies
- glomerulonephritis
- primaty nephritic syndrome
- membranous nephropathy
-focal segmental sclerosis
-amyloidosis of the kidneys
2. Tubulopathies
-acute tubular necrosis (acute renal failure)
-chronic tubulopathies (gout nephropathy, nephropathy in multiple myeloma)
3. Interstitial diseases
-tubular interstitial nephritis
-pyelonephritis
4. Nephrolithiasis
5. Nephrosclerosis
6. Benign and malignant
7. Congenital and hereditary diseases of kidneys
1. GLOMERULOPATHIES
are characterized by predominant lesion of glomeruli. These include in themselves glomerulonephritis, primary (idiopathic) nephrotic syndrome, focal segmental glomerulosclerosis and glomerulohyalinosis, amyloidosis of the kidneys.
a) Glomerulonephritis manifests itself by apyetous bilateral immunogenic inflammation of glomeruli caused by infectious and non-infectious agents. The disease occurs mostly in young people (below 20 y.o). At present three main forms of glomerulonephritis are differentiated:
- acute,
- subacute and
- chronic
Infectious glomerulonephritis predominates and develops first of all due to beta-hemolytic streptococcus infection (after streptococcal tonsillitis, erysipelas, streptococcal sepsis, streptococcal infection of the upper respiratory tract). Besides streptococci some other microbes take part in the development of glomerulonephritis: pneumoccoci, mycoplasms, viruses. Non-infectious glomerulonephritis develops seldom and is caused usually by chronic intoxication by ethanol.
In about 80-85% of cases glomerulonephritis is caused by circulating immune complexes (CIC). These consist of microbial antigens, antibodies and complement. CIC affect glomerular capillaries and evoke inflammation in them. In chronic alcoholics suffering from alcohol hepatitis glomerulonephritis can be caused by CIC containing (as an antigen) an alcohol hyalin. The type of inflammatory reaction depends on the size and structure of CIC, on the properties of antigens and components of complement system. In view of this clinic-morphological forms of glomerulonephritis and their outcome are different.
In 15-20% of patients glomerulonephritis is caused by autoantibodies which affect the basement membrane of glomerular capillaries. The classic example of subacute autoantibody glomerulonephritis is Goodpasture’s pneumo-renal syndrome (hemorrhagic interstitial pneumonia with extracapillary crescentic glomerulonephritis, see below) .
Pathomorphological changes of kidneys in glomerulonephritis.
In acute glomerulonephritis kidneys are slightly oedematous and enlarged with subcapsular hemorrhages; the cortex is pale, pyramids are hyperemic. But not rare kidneys may look normally and the diagnosis of glomerulonephritis can be put only in microscopic examination. Inflammatory exudation in glomeruli can be different (serous, hemorrhagic, fibrinous), but never purulent (i.e. apyetous), since neither CIC nor autoantibodies do not contain living microbes. Exudative phase of inflammation lasts for few days and after that changes into proliferative one. The latter manifests itself by proliferation of endothelial cells and mesangial macrophages which phagocytize immune complexes and clean glomeruli from them. Due to it in most of patients acute glomerulonephritis ends by spontaneous self-healing (the total morbidity in acute glomerulonephritis is about 5%). If mesangial macrophages can not eliminate CIC (incomplete phagocytosis due to local immune deficiency) inflammation in glomeruli becomes chronic (chronic glomerulonephritis) and finally ends by glomerulosclerosis.
In the most severe forms of acute glomerulonephritis with acute renal failure (malignant glomerulonephritis) partial or total necrosis of glomeruli develops because of thrombosis of glomerular capillaries.
Severe disturbances of hemocirculation in glomeruli stimulate production of renin which activates transformation of angiotensinogen into angiotensin. It results in increase of arterial blood pressure with hypertrophy of the left ventricle and clinical picture of secondary arterial hypertension.
Causes of death in acute glomerulonephritis:
- acute renal failure,
- hemorrhagic stroke,
- myocardial infarction (due to prominent hypertrophy of the left ventricle and arterial hypertension).
In subacute glomerulonephritis kidneys are enlarged and flabby, the cortex is wide, oedematous, yellowish-gray or even red. Microscopically intensive proliferation of epithelial cells of Bowman’s capsule is found with formation of “crescents” (crescentic glomerulonephritis). The latter compress glomerular capillaries which leads to rapid progression of renal failure (rapidly progressive glomerulonephritis). The disease develops mainly in middle aged and aged people and is caused by autoantibodies.
Chronic glomerulonephritis develops in patients without complete elimination of CIC from glomerular capillaries. It is differentiated into two forms – mesangial glomerulonephritis and fibroplastic (sclerotic) glomerulonephritis. Mesangial glomerulonephritis is subdivided into mesangial proliferative glomerulonephritis and mesangiocapillary ones. Mesangial proliferative glomerulonephritis is characterized by promuinent proliferation of mesangial macrophages but without thickening of the capillary basement membrane, while in mesangiocapillary glomerulonephritis the basement membrane of capillaries is very much thickened. Due to it glomerular filtration is seriously depressed which leads to progressive renal failure.
Fibroplastic glomerulonephritis is characterized by sclerosis and hyalinosis of glomeruli. It is the final stage of all forms of chronic glomerulonephritis which end with chronic renal failure and uremia.
In the final stage of chronic glomerulonephritis kidneys are diminished with granulated surface due to atrophy and prominent growth of connective tissue (nephrosclerosis).
Besides glomerular lesions glomerulonephrites are accompanied by affection of tubular epithelium (hydropic and hyaline degeneration) and interstitial lymphoid cell inflammatory infiltration with loss of concentrative function of kidneys and low density of the urine (not more than 1010).
The clinical picture of glomerulonephritis is characterized by combination of renal and extrarenal symptoms. The renal symptoms are: oligourea, proteinurea, hematuria, cylindrurea. Extrarenal symptoms are: oedemas of the face, arterial hypertension, hypertrophy of the left ventricle, dysproteinemia, hyperazotemia and uremia.
b) Nephrotic syndrome (NS) is characterized by severe proteinurea, hypoproteinemia with dysproteinemia, hyperlipidemia with prominent increase of lipoproteins of low and very low density and formation of oedemas of hypoproteinemia origin. NS is subdivided into primary and secondary ones. The primary NS represents itself the original disease, the secondary one complicates by itself glomerulonephritis and amyloidosis of the kidneys.
Primary NS is much more common for infants (75% of cases). Macroscopically kidneys are enlarged, flabby and yellowish at a cut section. The disease is characterized by minimal structural changes of glomeruli (“disease of small pedicels of podocytes”) which can be found only in electron microscopy. In a norm podocytes with their small pedicels regulate the process of glomerular filtration of the blood by means of influence on capillary permeability. In primary NS small pedicels are underdeveloped (congenital abnormality of podocytes is discussed) or destroyed, in view of this permeability of glomerular capillaries abnormally increases. In initial stages of the disease prominent loss of proteins (albumins) with the primary urine is compensated by their intensive tubular reabsorption. The latter leads to severe hydropic and lipid degeneration of tubular epithelium with subsequent loss of their function. As a result of it uncontrolled proteinurea develops with the loss of blood proteins up to 10 gr per day. Marked loss of blood proteins leads to the secondary immunodeficiency with high risk of secondary infections. Primary NS is more common for infants (75% of cases).
c) Membranous nephropathy is diagnosed mainly in adults (usually in males). The mechanism of the disease is conditioned by CIC. Macroscopically kidneys are enlarged, the surface is smooth, pinkish or yellowish. Microscopically a prominent thickening and hyalinosis of glomerular capillary basement membranes is seen but without any inflammatory changes (irrespective of immune complexes deposits). Clinical picture is characterized by proteinurea and hypoproteinemia with oedemas and ascites. In the last stage of the process nephrosclerosis develops with chronic renal failure.
d) Amyloidosis of the kidneys. Kidneys suffer in almost all cases of the secondary and [primary amyloidosis. In the first stages of the process kidneys are slightly enlarged, the cortex is broadened and pale, in the last stages contraction of kidneys develops. Four clinico-morpholopgical stages of the disease are differentiated: latent, proteinuric, nephrotic and uremic. In the latent stage amyloid mass are found around the basement membranes of glomerular capillaries. Later on amyloid deposits can be seen around basement membranes of cortical and medullar tubules with loss of reabsorption function and severe proteinurea (proteinuric and nephrotic stages). Total or subtotal affection of glomeruli is found in uremic stage with progressive renal failure.
2. TUBULOPATHIES. It is a group of renal diseases characterized by predominant lesion of tubules. Acute and chronic tubulopathies are differentiated.
a) Acute tubulopathies are represented by acute tubular necrosis (ATN) with acute renal failure. There are two main mechanisms of ATN – ischemic and nephrotoxic.
Ischemic type of ATN develops in renal ischemia of different origin: massive loss of blood, bilateral thrombosis of renal arteries, shock of different genesis (sepsis, diffuse peritonitis, profuse diarrhea with severe loss of water, cardiogenic shock in myocardial infarction).
Nephrotoxic ATN develops in acute or chronic intoxication with some chemicals (HgCl2, HCL, H3PO4) and medicines (high doses of paracetamol, sulfanilamides, barbiturates), in pathological conditioned with high level of myoglobine (traumatic and non-traumatic rhabdomyolysis).
Three stages of ATN are differentiated: initial (shock stage), oligoanuric and the stage of reparation.
Morphologically the initial stage of ATN is characterized by prominent venous hyperemia of the corticomedullar zone and pyramids but paleness of the cortex. Tubular epithelium undergoes dystrophy and necrosis.
In oligoanuric stage the kidneys are enlarged because of interstitial oedema of the stroma. Becides necrosis of tubules multiple hemorrhages in the stroma with inflammatory infiltration are found. In HgCl2 intoxycation massive deposits of lime salt can be seen in the foci of necrosis; in cases of intensive intravascular hemolysis multiple hemoglobin cylinders in the tubules are present.
The stage of reparation is characterized by regenerative processes in the tubules in the form of intensive proliferation of tubular epithelium. However complete reparation of the kidney structure does not occur, so in the end of the process nephrosclerosis with chronic renal failure develops.
b) Chronic tubulopathies are represented by impairment of kidneys in gout and multiple myeloma.
Gout is characterized by constant hyperuricemia as a result of specific enzymopathies related with X-chromosome. Due to it the disease is transmitted by mothers to mail newborns. In such condition with years excessive quantity of ureic acid forms crystal-like deposits in the parenchyma of the kidney with subsequent inflammation in the stroma. Not rare ureic acid forms uric gravels in the calices and pelvis. Secondary pyelonephritis is a typical complication of gout tubulopathy.
Impairment of kidneys in multiple myeloma (MM) is found in about 50% of patients with MM. The disease is characterized by intensive synthesis of paraproteins (light chains of IgG) which is excreted through kidneys with formation of multiple proteinaceous cylinders in tubules. The cylinders obdurate the lumen of tubules and impede the urinary outflow with subsequent renal failure. Besides that in great proportion of patients the secondary amyloidosis of kidneys develops.
3. INTERSTITIAL NEPHRITIS is characterized by predominant involvement into inflammatory process of the renal stroma (interstitium). Two main forms of interstitial nephritis are differentiated – tubular/interstitial nephritis and pyelonephritis.
а) Tubular/interstitial nephritis (TIN) is characterized by inflammation of the interstitium with synchronous affection of tubules. ТIN may be caused by different medicines (especially nephrotoxic antibiotics), some viruses and bacteria, different allergens and X-rays. The principle mechanism of TIN development is closely related with allergy.
In acute TIN inflammatory inflammatory oedema with infiltration by lymphocytes, monocytes and plasma cells develops. In drug-induced TIN eosinophils and non-specific granulomas can be found. In some cases necrosis of pyramid nipples is possible. Chronic TIN manifests itself by progressive nephrosclerosis.
b) Pyelonephritis represents itself microbe-induced inflammation of the kidney stroma, calyxes and pelvis. Microbes (usually representatives of intestinal group) enter the kidneys form the blood (hematogenic or descending pyelonephrotis) and from the urinary bladder in patients with disturbed urinary outflow: nephrolithiasis, enlarged prostate gland, nephroptosis, congenital stricture of the urether (ascending pyelonephritis). As pyelonephritis is caused by living bacteria (in contrast to glomerulonephritis) inflammation of the renal stroma in acute forms of the disease is usually purulent.
In acute pyelonephritis kidneys are enlarged, the cortex is uneven and contains scanty or multiple apostems (abscesses), calyxes and pelvis contain pus. In the most severe forms of acute pyelonephritis complete destruction of the cortex may develop.
In chronic pyelonephritis kidneys are tuberous and contracted, the cortex is atrophic and narrowed, calyxes and pelvis are dilated. In most cases of chronic pyelonephritis the renal parenchyma is sterile that supposes the role of immunogenic inflammation. Microscopically inflammatory infiltration is represented by lymphocytes and monocytes, the stroma is sclerotic, tubules look atrophic and contain numerous hyaline cylinders (“thyroid kidney”). At present chronic pyelonephritis is the most common cause of chronic renal failure in adults.
4. NEPHROLITIASIS (urolithiasis). It is a chronic disease of the kidneys and urinary tract which manifests itself by formation of calculi (stones) of different chemical composition. This process results from many local and general factors. The general factors are: genetic predisposition, predominance of proteins of the animal origin and carbohydrates in the meal, hypovitaminosis A, hard water. Local factors are: chronic inflammatory processes in the kidneys and urinary bladder, obstruction of the urethra due to enlarged prostate gland.
Due to chemical composition of stones these are subdivided into urates, phosphates and calcified stones. Urinary calculi usually cause obstruction of the ureter with urine congestion in the kidneys. The latter results in dilation of the calyxes and pelvis with atrophy of the renal parenchyma (hydronephrosis) and chronic renal failure. In some patients hydronephrosis may be complicated by secondary pyogenic infection with suppuration and pyonephrosis.
5. NEPHROSCLEROSIS manifests itself in bilateral atrophy and prominent sclerosis of the renal parenchyma. Two principle forms of nephrosclerosis are differentiated – primary and secondary ones. Primary nephrosclerosis develops as a result of progressive tissue ischemia in renal form of arterial hypertension (arteriolosclerotic nephrosclerosis) and constrictive atherosclerosis of renal arteries (artherosclerotic nephrosclerotic). In arteriolosclerotic nephrosclerosis kidneys are symmetrically diminished with microgranulated surface. In artherosclerotic nephrosclerotic contraction of kidneys is uneven with multiple scars and depressions.
Secondary nephrosclerosis develops as a result of chronic progressive glomerulonephritis, pyelonephritis, diabetic glomerulosclerosis, amyloidosis of the kidneys. In some cases secondary nephrosclerosis results from toxic affection of kidneys (acute tubular necrosis).
Severe nephrosclerosis always leads to chronic renal failure (uremia).
6. Uremia represents itself a clinic-morphological manifestation of chronic renal failure with prominent increase of urea and other toxic metabolites in the circulating blood. Uremia develops usually in patients suffering from chronic glomerulonephritis, pyelonephritis, polycystic disease and nephrosclerosis. In uremic patients urea and other metabolites undergo extrarenal excretion by sweat glands of the skin, mucous glands of the stomach and the gut, bronchial glands and alveolar parenchyma of the lungs, serous membranes (peritoneum, pleura and pericardial sack). Due to it pathomorphological picture of uremia in the most typical cases is characterized by formation of the salt deposits on the skin (“uremic powder”), uremic fibrinous gastritis and colitis, serous, fibrinous and hemorrhagic bronchitis and pneumonias, non-infectious fibrinous pleuritis, pericarditis and sometimes focal peritonitis. At present due to effective treatment of uremic patients pathomorphological picture of uremia is indistinct.
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