MINISTRY OF PUBLIC HEALTH OF UKRAINE
BUKOVINIAN STATE MEDICAL UNIVERSITY
Approval on methodological meeting
of the department of pathophisiology
Protocol №
Chief of department of the pathophysiology,
professor
Yu.Ye.Rohovyy
“___” ___________ 2008 year.
Methodological Instruction
to Practical Lesson
Мodule 2 : PATHOPHYSIOLOGY OF THE ORGANS AND SYSTEMS.
Contenting module 6. Pathophysiology of digestion, liver and kidney.
Theme 17: Pathophysiology of the kidney-2
Chernivtsi – 2008
1.Actuality of the theme. Glomerulonephritis is a bilateral disease of
the kidneys of the inflammatory origin. There are acute and chronic (diffuse)
glomerulo-nephritis. Experimental models. In 1901 V.K. Linderman observed
the main manifestations of nephritis in the rabbit in the intravenous introduction
of nephrotoxic serum of the guineapig immunized with si spension of the rabbit
kidney. In 1933 by using the same scheme of experiment, the Japanese scientist
Masugi reproduced the clinical piсture of nephritis in rabbit by introducing
serums of the duck blood immunized with the tissue of the rabbit's kidneys.
Masugi received another variant of nephritis model in the scheme rat - rabbit rat. At presence there are two phases of pathogenesis of the experimental
glomerulonephritis: heterologic conditioned by fixation of the nephrotoxic
antibodies (IgG, IgM) on the basal membrane оf the glomeruli of the nephrons
and autologic connected with production of complement-fixing antibodies for
nephrotoxic globulin.
2.Length of the employment – 2 hours.
3.Aim:
To khow: mechanisms of the acute pyelonephrities and nephrolytiasis.
To be able: to analyse of the development of the renal syndromes: urinary,
nephrotic, hypertension
To perform practical work: to analyse the mechanisms the development of
the glomerulonephrities.
A. Membranoproliferative GN, showing mesangial cell proliferation, basement
membrane thickening, leukocyte infiltration, and accentuation of lobular
architecture. B. Schematic representation of patterns in the two types of
membranoproliferative GN. In type I there are subendothelial deposits; type II is
characterized by intramembranous dense deposits (dense-deposit disease). In both,
mesangial interposition gives the appearance of split basement membranes when
viewed by light microscopy.
4. Basic level.
The name of the previous
disciplines
1.
histology
2.
biochemistry
3.
physiology
The receiving of the skills
Schematic diagram of a lobe of a normal glomerulus.
Determination of clearance index.
Renin-angiotesin system, prostaglandins.
Homeostasis (isovolemia, isotonia, isoionia,
isohydria).
5. The advices for students.
1. Acute (diffuse) glomerulonephritis.
In 1901 V.K. Linderman observed the main manifestations of nephritis in
the rabbit in the intravenous introduction of nephrotoxic serum of the guineapig
immunized with si spension of the rabbit kidney. In 1933 by using the same
scheme of experiment, the Japanese scientist Masugi reproduced the clinical
piсture of nephritis in rabbit by introducing serums of the duck blood immunized
with the tissue of the rabbit's kidneys. Masugi received another variant of nephritis
model in the scheme rat - rabbit - rat.
At presence there are two phases of pathogenesis of the experimental
glomerulonephritis: heterologic conditioned by fixation of the nephrotoxic
antibodies (IgG, IgM) on the basal membrane оf the glomeruli of the nephrons and
autologic connected with production of complement-fixing antibodies for
nephrotoxic globulin.
Etiology.
Acute glomerulonephritis arises in (or after) some infection, mostly of
streptococcus nature. It is considered, that hemolytic streptococcus of group A is a
specific "nephritogenic" strain. Other infections play definite role, including
viruses, parasites. Glomerulonephritis may arise in cooling, diffuse lesions of the
connective tissue (lupus erythematosis, rheumatoid arthritis, nodular periartteritis),
heterologic serum used in therapy, bums.
2. Two main mechanisms of damage of the glomeruli.
1. Affection of the basal membrane of the glomeruli of the nephrons by
antibodies its antigens - nephrotoxic glomerulonephritis (it has a quick progressive
course). Glycoprotein as a carrier of antigenic proteins of the basal membrane.
2. Development of the inflammatory process in the glomeruli due to fixation
of the immune complexes on the basal membrane -immunocomplex
glomerulonephritis.
The mechanism is characterized by either exogenic (of infectious or non
infectious origin) or endogenic (tissue protein, DNA) antigen. The formed
antibodies (IgG, IgM) begin to interact with the mentioned antigens in blood serum
and then as immune complexes (antigen-antibody-complement) enter the glomeruli
accumulating on their basal membrane. The impairment of the immune complexes
and nephrotoxic antibodies is realized by induction of the immune inflammation.
Glomerulonephritis developing after the streptococcal infection, in systemic lupus
erythematosus, serum disease and others is related to the immune complexes.
Clinical and pathophysiological manifestations of acute glomerulonephritis reflect
changes of the renal, mainly glomerular and extrarenal functions. The classical
course of the disease is characterized by violent onset, oliguria, proteinuria,
hematuria, azotemia, arterial hypertension, edemas which develops due to
retention of sodium, hypoproteinemia, hypervolemia, and increased permeability
of capillaries and disturbance of the nervous system.
3.Chronic (diffuse) glomerulonephritis.
Chronic glomerulonephritis may result from acute one, but more often they
develop primary. There are the following forms of the acute glomerulonephritis:
1. Of infectious origin (poststreptococcal, in malaria, syphilis, tuberculosis).
2. Non-infectious (serum, vaccine, medicamentous, in intoxication by
different poisons, traumatic, in thrombosis of the renal veins).
3. In diffuse diseases of the connective tissue (rheumatoid arthritis, lupus
erythromatosus, hemorrhagic vasculites, etc.)
4. Special (radiation, hereditary etc.)
Pathogenesis.
Hypersensitivity of the delayed type plays a certain role. The following forms
are distinguished clinically in the functional compensatory phase:
1.Latent (65% of all cases with chronic glomerulonephritis) from is
manifested by isolated urine syndrome -moderate proteinuria, hematuria. Some
patients (20-25%) are observed to have edemas and transitory hypertension.
2.The hypertensive (32% of patients) from is characterized by stable
increase of the arterial pressure. 1/3 of patients have edemas, 2/3 - hematuria, all
patients have proteinuria and half of them have cylinduria and leucocyturia.
3. The nephrotic form (2-4% of patients) form which is distinguished by
edematous syndrome (2/3 of patients) marked proteinuria and cylinduria (in all
patients) and characteristic changes in blood (hyperproteinemia and
hyperhpidemm)
4. Mixed of nephrotic hypertensive (24% of patiemts) from which is characterized by edemas and hypertension (in all patients).
4. What are some consequences of acute renal failure? The consequences
may be uremia.
5. What is uremia? The glomerular dysfunction is a delay of excretion of
products of nitrous metabolism from the organism and increase of their
concentration in blood. It is caused by accumulation of urea in blood. Urinary acid,
creatine, creatinine, ergothianine, ammonia, aminoacids and also toxic products,
formed in intestines such as phenol, indole and others.
6. State the outcome of chronic renal failure. Chronic renal failure
symptoms and signs usually do not develop until GFR declines to 25 % of normal.
The chronic alteration is primarily because of loss of nephron mass. The clinical
manifestations of chronic renal failure are described as uremia. The uremic state is
characterized by a decline in renal function and the accumulation of toxins in the
blood. If the lesions are tubular, then electolyte imbalances, volume depletions, and
metabolic acidosis occur. In glomerular lesions, hematuria and nephrotic syndrome
develop.
7. Identify and explain key features of nephrotic syndrome. In nephrotic
syndrome, there is increased glomerular permeability and protein leakage of 3.5 g
or more in the urine per day. The key features of nephrotic syndrome include
proteinuria, edema, hypoalbuminemia, hyperlipidemia, and lipiduria. Proteinuria
occurs with protein leakage from the serum into the urine; this process reduces
blood oncotic pressure. Thus, water leaves the capillaries more easily and tissue
edema follows. The edema is soft, pitting, and generalized. Hypoalbuminemia
develops as albumin leaks through the capillaries and depletes its serum level.
Hyperlipidemia occurs as the liver responds to the hypoalbuminemia by
synthesizing replacement albumin.While synthesizing albumin, the liver also
synthesizes lipoproteins in large amounts; therefore, hyperlipidemia develops. As
tubular cells containing fat are sloughed into the urine, lipiduria can be seen. Also,
free fat from the hyperlipidemia leaks across the glomerulus. Loss of protein
immunoglobulins increases susceptibility to infection in nephrotic syndrome.
Treatment is with a normal protein, low-fat diet; salt restriction; diuretics; steroids;
and occasionally, albumin replacement.
5.1. Content of the theme. Describe the types of glomerulonephritis,
their features, manifestations and treatment. What are some consequences of acute
renal failure? What is uremia? What are the most prominent symptoms and signs
of uremia? State the outcome of chronic renal failure. Identify and explain key
features of nephrotic syndrome.
5.2. Control questions of the theme:
1. Acute (diffuse) glomerulonephritis.
2. Two main mechanisms of damage of the glomeruli.
3.Chronic (diffuse) glomerulonephritis.
4.What are some consequences of acute renal failure?
5.What is uremia?
6.State the outcome of chronic renal failure.
7.Identify and explain key features of nephrotic syndrome.
5.3. Practice Examination.
Task 1. The patient with acute renal failure has arisen unuria (daily urine - 50 mls).
What from the here in provided of mechanisms bases of it formation?
A. Decrease of glomerular filtration B. Increase of sodium reabsorption
C. Difficulty of outflow of urine D. Disturbance of blood circulation in
kidney E. Increase of water reabsorption
Task 2. At examination ill, which one has transferred an angina in the acute form ,
the edemas, increase of arterial pressure, proteinuria, hematuria, decrease
of a diuresis are detected. These signs are characterized for an acute
glomerulonephritis. In the basis it is the immune destruction of basal
membrane of glomuluses, more often on the mechanism lies
A. Allergy of an anaphylactic type B. Allergy of cytotoxic type
C. Immunocomplex type D. Hypersensivity of delayed type
E. Stimulating type of allergy response
Task 3. The patient with chronic glomerulonephritis the anemia is detected. It is
arose
A. Loss of erythrocytes with urine B. Decrease synthesis of erytropoietine
C. Deficit iron in an organism D. Intensive hemolysis of erythrocytes
E.Schorteness of erythrocytes life
Task 4. The patient which the nephrolithiasis in blood and urine is increased the
contents of uric acid sharply. It is possible to expect, that the lithates in
him consist predominantly from
A. Sodium phosphases B. Sodium oxalates C. Lithates D. Carbonates
E. Cholesterol
Task 5. In a urine ill the proteinuria (6 g/l, proteins low molecular weight) and
hematuria (erythrocytes alkalinezed) is found. Protein and the erythrocytes
have appeared in a urine of
A. Depressing a of protein reabsorption B. Increase of canalicular
secretion C. Increase of glomuluses permeability D. Hypertension in
renal capillaries E. Damage of urinary pathways
Task 6. The patient with chronic renal failure has a high level of arterial pressure.
A major factor of increasing of pressure is in that case
A. Increase of cardiac output B. Hyperproduction of catecholamines by
adrenals C. Increase of renin synthesis D. Excess of antidiuretic
hormone E. Increase of vasoconstrictive tone
Real-life situations to be solved:
Task 1. In the patient with chronic glomerulonephritis the pains in muscles and
joints, itch of skin, ammoniated odor from a mouth have appeared. The residual
nitrogen of a blood was increased with 82 up to 216 mmol/l. The relative density
of the urine within a week was retained at a level 1,005-1,007.
1. Eveluate dynamic of disease.
2. In the expense of what the residual nitrogen of blood was increased?
3. About testify the values of relative density of urine?
4. Evaluate appearance of pain in joints and muscles.
. What arose an itch of skin in the patient?
. What an ammoniated odor associated from mouth with?
Task 2. The patient has entered clinic in a comatose condition. Breathing rare,
deep, face cyanotic – yellow-pail of colour, pupils narrow, skin dry. On body
hemorrhagic standing of different kind and remoteness scratch. Temperature of
body 38,8. Sharp odor of urine from the mouth. AP is 145/105 mm Hg. A residual
nitrogen of the blood of 234 mmol/l. The contents of the urea and creatinine is
increased. Quantity of erythrocytes in the blood - 2,0. 1012/l, hemoglobin content 50 g/l, quantity of thrombocytes - 70 .109/l.
. What the condition are peculiar these changes for?
. On the basis of what characterized signs it is possible it to confirm?
Literature:
1.Gozhenko A.I., Makulkin R.F., Gurcalova I.P. at al. General and clinical
pathophysiology/ Workbook for medical students and practitioners.-Odessa, 2001.P.223-226.
2.Gozhenko A.I., Gurcalova I.P. General and clinical pathophysiology/ Study
guide for medical students and practitioners.-Odessa, 2003.- P.290-299.
3.Robbins Pathologic basis of disease.-6th ed./Ramzi S.Cotnar, Vinay Kumar,
Tucker Collins.-Philadelphia, London, Toronto, Montreal, Sydney, Tokyo.-1999.