THE KIDNEY PATHOPHYSIOLOGY OF FILTRATION ABNORMALITIES BY DR RAANA AKHTAR PATHOLOGY DEPARTMENT. KEMU.

THE KIDNEY INTRODUCTION >1700liters of blood/day into about 1 liter of urine. Excretes the waste products of metabolism,urea and uric acid. Regulates conc.of salt and water Maintains the acid base balance, reabsorb bicarbonate from urine &excrete hydrogen ions Endocrine function,secretes hormones as erythropoietin calcitriol,renin and prostaglandins

MORPHOLOGY OF KIDNEY

GLOMERULI. TUBULES. INTERSTITIUM. BLOOD VESSELS. Glomerular diseases are immunologically mediated. Tubular and interstitial disorders caused by toxic or infectious agents. Damage to one effects the others

NEPHRON STRUCTURE

RENAL CORTEX

RENAL MEDULLA

RENAL GLOMERULUS

GLOMERULAR CAPILLARY WALL FILTERING MEMBRANE Fenestered endothelial cells(each fenestrum 70 to100nm in diameter. Glomerular basement membrane (GBM). Thick central layer,the lamina densa. Thinner peripheral layers, lamina rara interna & lamina rara externa. Visceral epithelial cells( podocytes and 20 to30 nm wide filtration slits bridged by diaphragm) Mesengeal cells lying between capillaries,are contractile, phagocytic,capable of proliferation of laying down both matrix and collagen& secreting mediators.

GLOMERULAR CAPILLARY MEMBRANE

GLOMERULAR FILTER

GLOMERULAR BASEMENT MEMBRANE (GBM) The GBM consists of : Collagen (mostly type IV), laminin, polyanoinic proteoglycans (mostly heparin sulphate)and glycoproteins (laminin,entactin). Type IV collagen forms network suprastructure The building block of this network is triple-helix made up of three alpha chains( alpha1 to alpha 6 or COL4A1 to COL4A6 ) of one or more types. Each mol.has 7S domain at N terminus, triple helix domain in the middle and non-collagenous domain(NC1) at the c terminus. Glycoproteins and proteoglycans attach to the collagenous suprastructure.

PROTEINS OF GLOMERULAR SLIT DIAPHRAGM

PATHOGENESIS OF GLOMERULAR INJURY ANTIBODY-MEDIATED INJURY. 1. IN SITU IMMUNE COMPLEX DEPOSITION Antibodies reacting in situ within the glomerulus, either binding to -Fixed intrinsic tissue antigens.(NC1, Heymann) -Planted antigens. Exogenous (infectious agents, drugs) Endogenous (DNA, nuclear proteins,Igs, immune complexes)

PATHOGENESIS OF GLOMERULAR INJURY 2. CIRCULATING IMMUNE COMPLEX DEPOSITION -Endogenous antigens (DNA, tumor antigens) -Exogenous (microbial products, bacterial products, viral antigens, antigens of T.P. and P.F. ) 3. CYTOTOXIC ANTIBODIES against glomerular cell components

Immune complex GN – “granular pattern” on immunofluorescense

Anti-GBM GN – “linear pattern” on immunofluorescense

EPITHELIAL CELL INJURY Can be induced by Antibodies to visceral epithelial cell antigens Toxins (drugs) Cytokines Other factors

EPITHELIAL CELL INJURY

Acute Proliferative Glomerulonephritis (APGN). Commonest cause of Nephritic Syndrome Poststreptococcal, Postinfectious. Rapidly Progressive Crecentic GN. Poststreptococcal GN: Diffuse proliferation of glomerular cells and influx of leucocytes. Caused by immune complexes. Antigen may be exogenous or endogenous.

Membranous GP commonest cause of NS in white adults, but also seen in all other races: mostly middle- aged/elderly Ag/Ab complexes again - long term deposition in 85% cases, Ag in complex is unknown (“idiopathic membranous GN”),

Known immune complex associations in membranous GP infections (hepatitis B, malaria, syphilis, schistosomiasis) drugs (e.g. penicillamine, NSAIDs) inorganic metals (gold, mercury) malignant tumours (e.g. lung, lymphoma, colon) autoimmune diseases (thyroiditis, SLE)

Membranous GP - uniform diffuse thickening of glomerular capillary wall

Pathophysiology of MCD UNC UNC Medical Center

A. MINIMAL CHANGE DISEASE (lipoid nephrosis) 44