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Flashcards in Pathogenesis of Glomerular Disease Deck (22):

1. Define the basic terminology employed in glomerular disease. (mesangium, parietal epithelium, capillary tuft)

mesangium: mesangial cells and mesangial matrix; functions as the scaffold for the capillaries, may have some smooth muscle and draining functions

parietal epithelium= bowman's capsule

capillary tuft- capillaries that make up the glomerulus

BONUS: crescent- accumulation of cells in the Bowman's space (monocytes or Boowman's space


1. Review glomerular structure and function. Note the layers between blood supply and Bowman's capsule.

fenestrated endothelium (charge exclusion)
GBM: charge barrier (collagen IV and heparin sulfates) (charge exclusion)
visceral epithelial cells: podocytes with slit diaphragm of nephrin(size and charge barrier)


2. Summarize clinical findings associated with glomerular diseases.

hematuria- specifically dimorphic RBC or RBC casts
proteinuria- sulfosalicylic acid turbidity test (all proteins) or antibodies
renal failure


2. Describe the causes and ways of measuring hematuria and proteinuria in more detail.

hematuria: urologic (tumor or infection) or glomerulopathic (dysmorphic RBC, RBC casts); microscopic hematuria is detected with urinary sediment while macroscopic is visible to naked eye

proteinuria: glomerular permeability causes protein to leak into urine; detected by 24h urine collection (nephrotic range >3.5 g/24h)


3. Identify laboratory studies used in the diagnosis of glomerulopathies. (both nephritic and nephritic)

nephritic: UA (hematuria and proteinuria; oliguria), BP- **HTN, blood BUN and creatinine (azotemia)

nephrotic: UA (proteinuria >3.5g/d; lipiduria), lipid panel (hyperlipidemia) serum albumin (hypoalbuminemia)


4. Describe indications for the kidney biopsy.

best diagnostic tool for a glomerular disease (important in following tx. too)

suspected disease that call for renal biopsy: proteinuria, SLE, acute renal failure, hematuria, chronic renal failure, vasculitits


4. Describe interpretation of the kidney biopsy. (hint, what is evaluated?, what are examples of pathological findings?)

glomeruli, tubules and interstitial and vessels are evaluated looking for proliferation/infiltration of cells , capillary wall abnormalities and matrix/protein accumulation


5. List major pathological changes seen in glomerular diseases.

proliferation or infiltration of cells in the mesangium, in the capillary or both

capillary wall abnormalities: thickening of BM or deposition of proteins; intrinsic, structural GBM abnormalities like basket weave formation of Alport syndrome, amyloid deposition


6. Describe non-immunologic mechanisms of glomerular injury.

ischemia (i.e. atheromatous plaque): glomeruli become scarred with collagen
endothelial injury (i.e. cyclosporin or bacterial toxins): can cause clotting and ischemia
deposition of proteins (hyaline deposition, light chain or amyloidosis): mohawk of capillary loops, stippled pattern of the BM


6. Describe immunologic mechanisms of glomerular injury.

antibody-mediated (intrinsic, planted or circulating immune complexes)
alternative pathway of complement activation


Describe the clinical signs of a mixed nephritic and nephrotic syndrome. What diseases might cause this?

proteinuria >3.5 in the context of hematuria, renal failure and hypertension

diseases: Lupus nephritis, Membranoproliferative glomerulonephritis


What is the triple approach to examining a biopsy?

light microscopy
electron microscopy


What do H&E, PAS, Trichrome and HMS stains highlight about the glomerulus?

H&E shows overall structure
PAS: highlights membranes
Trichrome: highlights collagen
HMS: basement membrane is as a dark band


Additional study...

may be helpful to go over pathology slides in this lecture


Compare the mechanism that causes damage and the pattern of damage in nephrotic v. nephritic.

in nephritic syndrome there is widespread alteration of the capillary walls

in nephritic syndrome the 'holes' that lead to hematuria are due to inflammation


Describe the following terms used to denote the degree of involvement and distribution of lesions in glomerularnephritis.

focal: involving <50% of the glomuli
diffuse: involving 50%+ of the glomeruli

segmental: involving a portion of the glomerular tuft
global: involving the entire glomerular tuft


Describe the pathology that is characteristic of Membranoproliferative GN.

proliferation and GBM abnormalities


Give examples of antibody mediated immunologic injury in native antigen of glomerulus

Non-collagenous domain I (NCI) of the a3 chain of the collagen type IV is a major component of GBM to which autoantibodies and induce crescentic (extra capillary proliferation) glomerulonephritis (and lung): linear deposition


Give examples of antibody mediated immunologic injury in native antibody of glomerulus.

M-type phospholipase A2 receptor (PLA2R) is a protein on the surface of podocytes, binding of antibodies leads to idiopathic membranous glomerulopathy (sub epithelial deposition is less inflammatory leading to widespread loss of proteins)


Give examples of antibody mediated immunologic injury in circulating complex.

drug or virus protein can act as a planted antige (binds to GBM) leading to secondary membranous glomerulopathy

antigens (ie. bacterial proteins) can cause circulation immune complexes and complexes get trapped in glomerular capillary wall; leading to diffuse proliferative, post infectious GN (course granular deposits)

antibodies can block inhibitory binding in complement convertase and complement can accumulate in the glomerulus


Describe the sequelae of glomerular disease.

1. glomerulosclerosis: resulting irreversible scarring and hyalin deposition

2. interstitial fibrosis and tubular atrophy

causes of chronic GN include: post streptococcal GN, crescentic GN, membranous nephropathy, focal segmental glomerulosclorsis, membranoproliferative GN and IgAN


Describe the relationship between location of immune complexes and antigen location. (comparison of nephrotic and nephritic)

complexes in the podocytes are not exposed to circulation and do not show increased cellularity but do lead to proteinuria (nephrotic)

complexes deposited in sub endothelial layer elicit an inflammatory repines with increased cellularity and disruption of the capillary wall (nephritic)