Kidney

Question 1

Interstitium and cellularity of cortex and medulla

Answer 1

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.

Question 2

Diseases of the kidney can be divided into four major groups depending onthe basic morphologic components affected namely

Answer 2

1. Glomerular diseases
2. Tubular diseases
3. Interstitial diseases
4. Diseases of blood vessels

Question 3

Classify glomerular diseases

Answer 3

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

Question 4

Glomerulonephritis/glomerulopathies may show one or more of three basic
histological changes

Answer 4

1. 🔼 cellularity
2. Basement membrane thickening
3. Hyalinization or sclerosis.

Question 5

Increased Cellularity (Hypercellularity) of glomerulonephritis

Answer 5

🔼 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)

Question 6

Basement Membrane Thickening in glomerulonephritis

Answer 6

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)

Question 7

Hyalinosis of glomerulonephritis

Answer 7

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

Question 8

Sclerosis of glomerulonephritis

Answer 8

Accumulations of extracellular collagenous matrix, either in the mesangium (e.g., diabetic glomerulosclerosis) or in the capillary loops, or both

Question 9

Primary glomerulonephritis/ glomerulopathies

Answer 9

• 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

Question 10

Systemic diseases with glomerular involvement

Answer 10

• 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

Question 11

Hereditary glomerular diseases

Answer 11

• Alport syndrome
• Thin basement membrane disease
• Fabry disease

Question 12

Antibody-mediated glomerular injury can be produced by two mechanisms

Answer 12

1. Circulating (Ag-Ab) complex deposition in the glomerulus.
2. 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

Question 13

Circulating Immune Complex Glomerulonephritis

Answer 13

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

Question 14

Various immune mechanisms involved in glomerular injury

Answer 14

1. 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)
2. Cell-mediated immune injury
3. Activation of alternative complement pathway

Question 15

Antigens involved in glomerulonephritis mediated by immunocomplex

Answer 15

1. Endogenous: Autoimmune diseases (e.g., SLE)
2. 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.

Question 16

Immunocomplexes in glomerulonephritis are seen in

Answer 16

• 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

Question 17

Factors that Determine Localization of antigen, antibody, or immune complexes in the
glomerulus

Answer 17

1. 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.
2. 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

Question 18

Fate of immunocomplex deposits in kidney

Answer 18

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.

Question 19

Goodpasture syndrome

Answer 19

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

Question 20

Masugi or nephrotoxic nephritis

Answer 20

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.