GLOMERULAR DISEASEYousaf Khan Lecturer Renal Dialysis IPMS-KMU

GLOMERULAR DISEASE Group of disease Affect of glomerular and inflammatory in nature Immunologically mediated It may be primary or secondary.

PRIMARY GLOMERULAR DISEASE Minimal change glomerular disease Membranous glomerulonephritis Membranoproliferative glomerulonphritis IgA nephropathy Acute diffuseproliferative glomerulonephritis

SECONDARY GLOMERULAR NEPHRITISCommon SLE Polyarteritisnodosa Diabetes mellitus Amyloidosis Malarial nephropathy

Uncommon: Sarcoidosis Rheumatoid arthritis Hemolytic uremicsyndorm AIDS nephropaty

PATHOGENESIS 1. Circulating immune complex deposition:Antigen + Antibody – deposition in glomeruli – binding with complement – inflammation – glomerular injury. Antigen may be exogenous or endogenous

2. Antibodies directed against antigen on glomerular capillary membrane:

Anti – GBM antibody disease – antigen fixed in the GBM e.g good pasture syndrome

Antibodies against non GBM antigen

NEPHROTIC SYNDROMEClinical complex characterized by Heavy proteinuria (3.5 g/day) Hypoalbuminemia Edema Hypelipidemia Hyperlipiduria

Proteinuria: daily loss of protein 3.5 gm or more of protein Injury to the capillary wall of the glomeruli result –

increase permeability to the plasma protein – allow to – escape from plasma

PATHOGENESIS Hypoalbuminemia: Proteinuria – decrease serum albumin level

Generalized edema: Hypoalbuminemia – result decrease colloid osmotic

pressure

Hyperlipidemia: Hypoalbuminemia triggers increase sysnthesis of all form

of plasma protein including lipoprotein – hyperlipidemia.

Hyperlipiduria: Hyperlipoproteinemia – increase permeability results in

hyperliduria

ETIOLOGY OF NEPHROTIC SYNDROMEPrimary glomerular disease: Minimal change nephropathy Focal segmental glomerulosclerosis Membranous GN

Secondary GN associated with systemic disease: Diabetic nephropathy Amyloidoisis Drugs: penicillamine, gold, mercury, cadmium Allergic reaction

CLINICAL FEATURESEdema: Upper and lower limb Children more obvious on the face Intense edema of scrotum or vulva may occur Bilateral hydrothorax Edema of intestine causes anorexia, diarrhea and vomiting.

Malnutrition: Malnutrition may be due to protienuria, frequent infection

and muscle wasting.

Hypercoagulability: Hypercoagulability manifest as peripheral arterial or venous

thrombosis renal vain thrombosis and pulmonary embolism

INVESTIGATION Urine D/R – Proteinuria 24 hr urinary protien - > 3 g/day Serum albumin – less than 3 g/dl and total serum

protein < 6 mg/dl Low- density lipoprotien is elevated but HDL is usually

normal. Raised ESR due to increase serum fibrinogen Blood sugar for diabetes and antinuclear factor for

SLE. Serology and renal biopsy.

COMPLICATION AND MENAGEMENT Protein malnutrition Hypercoagulabilty – due to rise in many clotting

factors Impaired resistance to infection Sepsis, blood loss and hpovolemia may lead to acute

oliguric renal failure

Management: Diet Diuretics Hypercholesterlemia Hypercoagulability Oliguric renal failure

MEMBRANOUS GLOMERULONEPHRITIS Slowly progressive disease Most common between 30 to 50 year Characterized by diffuse thickening of GBM Cause by deposition of immune complex on

the epithelial side of the GBM.

ETIOLOGY Primary 85% membranous nephropathy caused

by autoantibodies that cross-react with antigens expressed by podocytes.

Secondary causes Infections (chronic hepatitis B, syphilis, malaria) Malignant tumors, particularly carcinoma of the

lung and colon and melanoma Systemic lupus erythematosus and other

autoimmune conditions Exposure to inorganic salts (gold, mercury) Drugs (penicillamine, captopril, nonsteroidal

antiinflammatory agents)

Pathogenesis: Membranous glomerulonephritis is a form of chronic

immune complex nephritis

Morphology:Feature of light microscope Diffuse thickening of glomerular basement membrane

Feature of electron microscope: Apparent thickening of GBM is caused by subepitheial

deposits that are separated from each other by small spike in GBM matrix.

CLINICAL FEATURE OF MEMBRANOUS GN Insidious development of nephrotic syndrome.

In contrast to minimal change disease the proteinuria is non selective (albumin and globulin both are excreted)

Usually does not response to corticosteroid therapy

About 40% lead to renal failure after 2- 20 years 60% although proteinuria persist yet they do not

progress to renal failure

NEPHRITIC SYNDROME Inflammatory process causing renal dysfunction Over days to week that may or may not resolve. More than 50% loss of nephron function

Characterized by Hematuria with RBC casts Proteinuria (usually non rephrotic range) Hypertension Edema Oliguria uremia

Glomerual disease with nephritic presentation

Post- Streptococcal GN IgA nephropaty Goodpasteur sysndrom Polyarteritits nodosa Acute interstitial nephritis

Investigation:Urinalysis Dysmorphic red cell Red cell cast Proteinuria

Serum chemistriesRenal biopsy

Treatment: Reduction of hypertension Salt water restriction Diuretics

RAPIDLY PROGRESSIVE GLOMERULONEPHITISYousaf Khan Lecturer Renal Dialysis IPMS-KMU

RPGN Clinical syndrome Characterized by loss of renal function Laboratory finding – nephritic syndrome – severe

oliguria About 50% cases are idiopathic while 50% are related

to the systemic disease. Histological finding associated with RPGN is the

presence of cresents

TYPES OF RPGNType I RPGN:Anti-GBM disease Characterized by deposition of IgG and C3 on GBM anti-GBM antibodies cross react with pulmonary alveolar basement

membrane –to produce clinical picture of pulmonary hemorrhage along with renal hemorrhage – good pasture syndrome.

Type II RPGN (Immune – complex mediated disease) Complication of any of immune complex nephritis such as

poststrptococcal GN, SLE, IgA nephropathy ets

Type III: Characterized by lack of anti GBM antibodies or immune complex

by immunoflurescent and electron microscope. In serum antineutrophilic cytoplasmic antibody Associated with some systemic vasculitis

MORPHOLOGY Presence of crescents in most of the glomeruli

Crescents are formed by proliferation of the parietal epithelial cells of bowman capsule

Crescents eventually obliterate the bowman space and compress the glomeruli resulting oliguria

CLINICAL FEATURE Like nephritic syndrome

But more marked oliguria and azotemia

90% patient required dialysis and transplantation.

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