Kidney Flashcards
Interstitium and cellularity of cortex and medulla
The interstitium in the renal cortex is scanty and consists of a small number of fibroblast-like cells whereas in the medulla, it is more and contains
stellate interstitial cells.
Diseases of the kidney can be divided into four major groups depending onthe basic morphologic components affected namely
- Glomerular diseases
- Tubular diseases
- Interstitial diseases
- Diseases of blood vessels
Classify glomerular diseases
Glomerular diseases may be broadly divided into primary and secondary:
1. Primary glomerulonephritis or glomerulopathy (those without
inflammatory cells):
Kidney is the only or predominant organ involved.
2. Secondary glomerular diseases:
In these disorders, glomeruli are
involved secondary to a systemic disease
Glomerulonephritis/glomerulopathies may show one or more of three basic
histological changes
- 🔼 cellularity
- Basement membrane thickening
- Hyalinization or sclerosis.
Increased Cellularity (Hypercellularity) of glomerulonephritis
🔼 in the number of cells in the glomerular
tufts called proliferative glomerulonephritis.
Hypercellularity may be due to:
1. Cellular proliferation: may involve any of the cells (3 types) of glomeruli
2. Leukocytic infiltration: include all
3. Formation of crescents: due to proliferation of parietal epithelial cells and infiltration by leukocytes (as a response to fibrin that leaks into the urinary space through ruptured BM)
Basement Membrane Thickening in glomerulonephritis
may be due to:
1. Deposition of amorphous electron-dense (immune complexes)
material:
may be on endothelial or epithelial side of GBM or within the GBM itself.
2. Thickening of the basement membrane (e.g., in diabetic glomerulosclerosis)
Hyalinosis of glomerulonephritis
Accumulation of homogeneous and eosinophilic material in the glomeruli and consists of plasma proteins that have leaked from the circulation into glomerular structures.
It is usually due to endothelial or capillary wall injury
Sclerosis of glomerulonephritis
Accumulations of extracellular collagenous matrix, either in the mesangium (e.g., diabetic glomerulosclerosis) or in the capillary loops, or both
Primary glomerulonephritis/ glomerulopathies
- Acute proliferative glomerulonephritis: Post-infectious, others
- Rapidly progressive (crescentic) glomerulonephritis (RPGN)
- Minimal-change disease (MCD)
- Membranous glomerulonephritis (MGN)
- Membranoproliferative glomerulonephritis (MPGN)
- C3 glomerulonephritis
- Dense deposit disease
- Focal segmental glomerulosclerosis (FSGS)
- Immunoglobulin A (IgA) nephropathy
- Chronic glomerulonephritis
Systemic diseases with glomerular involvement
- Systemic immunological diseases (e.g., SLE)
- Metabolic diseases (e.g., DM)
- Vasculitis: Microscopic polyarteritis/polyangiitis, Wegener granulomatosis, Henoch–Schönlein purpura
- Amyloidosis
- Goodpasture syndrome
- Bacterial endocarditis
Hereditary glomerular diseases
- Alport syndrome
- Thin basement membrane disease
- Fabry disease
Antibody-mediated glomerular injury can be produced by two mechanisms
- Circulating (Ag-Ab) complex deposition in the glomerulus.
- In situ antibodies: against:
• Fixed (intrinsic) glomerular antigens [e.g., antiglomerular basement
membrane (anti-GBM) Ab-induced glomerulonephritis] or
• Antigens which are planted within the glomerulus
Circulating Immune Complex Glomerulonephritis
Most of glomerulonephritis are immunocomplex mediated.
caused due to trapping of circulating immunocomplexes (type III hypersensitivity) within glomeruli.
Ab are not against any of glomerular
constituents, and the immune complexes localize within the glomeruli.
Ag may be of endogenous or exogenous origin
Various immune mechanisms involved in glomerular injury
- Ab-mediated injury:
In situ immune complex deposition
• Fixed intrinsic tissue Ag (e.g., anti-GBM)
• Planted antigens
– Exogenous (e.g., infectious agents, drugs)
– Endogenous (e.g., DNA, nuclear proteins)
Circulating immunocomplex deposition
• Endogenous Ag (e.g., DNA, tumor Ag)
• Exogenous Ag (e.g., infectious products) - Cell-mediated immune injury
- Activation of alternative complement pathway
Antigens involved in glomerulonephritis mediated by immunocomplex
- Endogenous: Autoimmune diseases (e.g., SLE)
- Exogenous:
• Microbial antigens:
� Bacterial products (e.g., streptococci)
� Viral antigen (e.g., hepatitis B virus, hepatitis C virus antigens)
• Spirochetal antigens (of Treponema pallidum)
• Parasitic: Plasmodium falciparum
• Tumor antigens
• Unknown antigen.
Immunocomplexes in glomerulonephritis are seen in
• Mesangium (mesangial deposits).
• Subendothelial deposits between the endothelial cells and the GBM.
• Subepithelial deposits between the outer surface of the GBM and the podocytes.
• Other site may be in the glomerular basement membrane or it may
be in more than one site mentioned above
Factors that Determine Localization of antigen, antibody, or immune complexes in the
glomerulus
- Molecular charge:
• Highly cationic molecules cross the GBM and appear subepithelially.
• Highly anionic molecules cannot cross GBM ➡️ trapped in subendothelially.
• Neutral molecules accumulate in mesangium. - Molecular size:
Large circulating complexes are removed from circulation by mononuclear phagocyte system ➡️
enter the GBM in sufficient quantities. ➡️ do not produce glomerulonephritis. 📝: Immune complexes of medium size and with slight antigen excess are the most pathogenic
Fate of immunocomplex deposits in kidney
The immunocomplexes may be degraded or phagocytosed, mostly by infiltrating leukocytes and mesangial cells. Further changes:
1. If the inciting antigen is short-lived and limited, the inflammatory
reaction may subside (e.g., most cases of PSGN or PIGN).
2. If exposure to antigen is sustained, there will be repeated cycles of
immune complex formation, deposition, and injury ➡️ chronic GN.
Goodpasture syndrome
Conformational changes
in the a3 chain of type IV collagen of GBM.
➡️ anti-GBM antibodies.
➡️ cross-react with not only renal GBM but also with basement membrane of 🫁 alveoli
➡️ simultaneous production of 🫁 and kidney lesions
Masugi or nephrotoxic nephritis
experimental model of
nephritis in 🐀
1. 🐀 kidney tissue is injected into the 🐇 to produce anti-🐭 kidney Ab
2. Injected into 🐀
3. anti-🐭 kidney Ab bind along the entire length of GBM ➡️ glomerular damage in 🐀
4. 🐀 anti-Ig Ab then react with the 🐰 Ig ➡️ further 🔼 glomerular damage.
