Glomerular diseases:

GLOMERULAR DISEASE

These consists of rapidly progressive glomerulonephritis (RPGN), nephrotic syndrome, acute nephritis and chronic glomerulopathies.

Primary glomerular diseases present clinically with (1) abnormalities of the urine, including proteinuria and hematuria, (2) hypertension, (3) edema and (4) reduced renal excretory function.

Continuous production of protein free filtrate across a glomeruli by specialized mechanism for clearing trapped molecules through the mesangium increase the susceptibility by trapping circulating macromolecules. Deposition or generation of immune complexes can cause complement fixation and activation of lymphocytes and macrophages, all of which can mediate damage. Even environmental toxins can also induce glomerulonephritis in goodpasture’s syndrome and this might be from damage to BM lining of the lung which has some antigenic epitopes similar to those of glomerular BM.

Glomerulonephritis can be subdivided immunologically into conditions mediated by antibodies against either extrinsic or intrinsic to the kidney. Extrinsic agents include micro-organisms or DNA as in SLE, intrinsic components includes glomerular basement membrane, leading to immune complex formation. Whatever the mechanism is, antigen-antibody complexes become trapped in glomerulus, activating both the classical and alternative complement pathways and leading to release of anaphylatoxic components like C3a and C5a. Anaphylatoxins, together with locally released kinins, prostaglandins and leukotrienes, attract polymorphonuclear neutrophils to basement membrane where the latter releases lysososmal enzymes, leading to membrane disruption and glomerular proteinuria. There may be loss of anionic charge associated with epithelial foot process can produce massive selective proteinuria while changes in basement membrane, tend to be associated with increasingly non-selective proteinuria.

The primary glomerulonephritis are classified morphologically according to histological analysis into.

Rapidly progressive glomerulonephritis:

This can lead to kidney failure in only weeks or a few months. These are characterized by focal necrotizing glomerulonephritis. In response to fibrinogen and fibrin polymers that are released after glomerular capillary injury, proliferating epithelial cells and macrophages (leaking from circulation, as well as resident) eventually compress the glomerulus and obstruct the PCT compromising nephron function. RPGN can be idiopathic or secondary to other conditions like infection, autoimmune immune complex deposition like antineutrophil cytoplasmic antibodies (ANCA).

Minimal change glomerulonephritis: 

During this condition there is little or no abnormality and no immunoglobulin or complement components. Proteinuria involves loss of fixed negative charge on glomerular basement membrane due to fusion of epithelial cell foot processes. This leads to selective proteinuria (mainly albumin).

Membranous glomerulonephritis: 

It is the commonest cause of nephrotic syndrome in adults. There is thickening of glomerular basement membrane. There is IgG deposits seen most commonly. It may also be associated with SLE where immune complexes formed in circulation deposits in GBM. There is massive proteinuria and poorly selective and some have asymptomatic proteinuria or microscopic hematuria. Proposed hypothesis is the role of extrinsic antigen deposition in the glomerulus with subsequent IC formation, glomerular trapping of circulating IC or antibodies binding to intrinsic glomerular antigens.

Proliferative glomerulonephritis: 

Here glomeruli appear hypercellular, due, for example, to invading macrophages or mesangial cells. Different disease can elicit immunologically mediated glomerular damage, including bacterial endocarditis, Group A streptococcal infection and SLE. There is frequent IgA, IgG and C3 deposits, and complement activation. Patients have proteinuria and microscopic hematuria and the proteinuria is predominantly non selective.

Focal and segmental glomerulonephritis: 

Here hyaline material is deposited in the subendothelial spaces of affected capillary in certain area thus called focal and segmental. Patients present with mild proteinuria or recurrent hematuria. The etiology is not known but is immune mediated.

Nephrotic syndrome:

Gross changes in glomerular permeability characterize the nephrotic syndrome. The diagnostic criteria for establishing nephrotic syndrome are presence of proteinuria (>3g/day or albumin >1.5 g/day), hypoalbuminemia, hypercholesterolemia (elevated LDL, VLDL), lipiduria and finally edema. Edema occurs due to expansion of interstitial compartment and accumulation of sodium also there is loss of plasma oncotic pressure due to loss of protein (albumin). 

Proteinuria is a consequence of loss of charge selective properties of filtration barrier. Nephrotic syndrome can result from minimal change nephropathy; focal segmental glomerulosclerosis, membranous nephropathy associated with carcinoma, drugs, SLE and DN or may be idiopathic. Hematuria is not seen because damage is not large enough to allow RBC and oliguria is uncommon.

Acute nephritic syndrome:

This is characterized by rapid onset of hematuria, proteinuria (usually <3g/day), Azotemia, reduced GFR, and Na and water retention with resulting hypertension, oliguria and edema. This can be caused by PSGN, SLE, etc. Infiltration of glomerular mesangium or capillary with PMN leukocytes and monocytes can cause damage. 

There is also deposition of immune complex in basement membrane. Nephritic syndrome is the progression of nephrotic syndrome and hypercellularity and inflammation is more in this condition.