Glomerular Structure and Mechanisms of Disease (Nichols) Flashcards by Charlie Duke

9 places in a glomerulus that disease can be located

1 arterioles
2 capillaries (lumen & endothelial cells)
3 subendothelial (btwn capilary endothelial cells & GBM)
4 GBM
5 subepithelial (btwn GBM & epithelial cells)
6 in slit pore diaphragm
7 podocytes
8 bowman space and capsule
9 mesangium

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8 most common primary glomerular diseases

1 minimal change disease
2 focal segmental glomerulosclerosis
3 membranous nephropathy
4 acute post-streptococcal glomerulonephritis
5 membranoproliferative glomerulonephritis
6 IgA nephropathy (Berger disease)
7 hereditary nephritis (Alport syndrome)
8 congenital nephrotic syndrome

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5 most common secondary glomerular diseases

1 hypertensive nephropathy
2 diabetic nephropathy
3 lupus nephritis
4 amyloidosis
5 Goodpasture syndrome

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3 most common types of glomerular disease in order of prevalence

1 hypertensive
2 diabetic
3 immune-mediated

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pathophys of hypertensive glomerular disease

most common cause of glomerular disease
injury to endothelium -> thrombus
thrombotic microangiopathy
positive feedback loop

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Malignant htn

black males ~40
intracranial pressure, headache, scotomas, vomiting
BP >200/120 mmHg
proteinuria, microscopic hematuria
fibrinoid necrosis of arterioles
proliferation of intimal cells in small arteries
hyperplastic arteriosclerosis 
     *onion-skin appearance*

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anti-GBM disease

More common in men as their GBM is thicker
associated with smoking
Tx by plasmapheresis

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podocyte disease

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crescentic nephritis

proliferative parietal epithelial cells, exudate, leaked plasma, visible crescent in BS

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slit pore diaphragm disease

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patterns and locations of immune complexes & diagnostic examples

mesangial - IgA nephropathy
subepithelial - post strep. glomerulonephritis
subendothelial - lupus

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foot processes

part of pedicles - interdigitates with another

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mesangium

mesanchymal cells
phagocytic
contractile
produce mesangial matrix

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GBM

glomerular basement membrane

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parlecan

basement membrane

highly charged w/heparan sulfate

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entactin

basement membrane

Ca++ binding

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fibronectin

basement membrane

high MW - binds collagen, heparan sulfate, integrins

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laminin

basement membrane - binds type IV collagen, entactin, heparan sulfate, and cells

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type IV collagen location & 2 types

basement membrane
alpha3, alpha4, alpha5 (IV)
alpha5, alpha5, alpha6 (IV)

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noncollagenous domain of alpha3 (IV) chain

antiodies attack in Goodpasture’s

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nephrin

transmembrane - major component of slit pore diaphragm. disulfide bridges

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podocin

part of split pore diaphragm

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metabolic (diabetic) nephropathy

hyperglycemia -> glycosylation of proteins
they get trapped in GBM, stim new GBM
GBM thickened
AGE & AOPP

diabetic protein glycosylation

non-enzymatic due to high glc

hemodynamic glomerular injury

pressure -> physical injury

diffuse vs focal glomerular disease

diffuse - most or all glomeruli | focal - few glomeruli

global vs segmental glomerular disease

global - the whole thing(s) | segmental - part of it (them)

proliferative glomerulonephritis

cells grow

membranous nephropathy

membrane thickening

membranoproliferative glomerulonephritis

both proliferative and membrane thickening

pauci-immune glomerulonephritis

no immunofluorescence most patients have ANCA pANCA cANCA

glomerulosclerosis

fibrous replacement of the glomerulus

glomerular basement membrane layers

``` lamina lucida/rara (close to endothelial cells) lamina densa (double usual thickness) lamina rara externa (close to epithelial cells) ```

non-glomerular basement membrane layers

``` lamina rara (close to endothelial cells) lamina densa ```

Goodpasture syndrome

antibodies against alpha3 (IV) non-collagenous NC domain

antibodies to non-collagenous collagen

antibodies against alpha3 (IV) non-collagenous NC domain

how is African sleeping sickness circumvented?

Disease is caused by Trypanosoma brucei rhodesiense variant apoL1 doesn't bind trypanosomal protein, which would ordinarily lyse parasites. Mutation associated with focal segmental glomerulosclerosis

foot process effacement

long segments of a capillary are covered by a single podocyte - no longer interigitating foot processes

nephrotic syndrome

severe loss of protein through slit pore diaphragms - shows effacement

FAT & cadherin function

binds adjacent pedicles

nephrin

transmembrane filtration role in slit-pore diaphragm disulfide bridges

IgA nephropathy

abnormal IgA - uncapped in hinge region reduced negative charge allows filtration binds IgA, fibronectin, CD89 (soluble IgA receptor), transferrin receptor (CD71) on mesangial cells compliment activated 75% lectin, 25% alt. anaphylotoxins, injury/inflammation

immune-mediated glomerular disease

fixed or planted antigens directly toxic or (more likely) elicit leukocyte damage platelets aggregate IL-1 release, arachidonic acid metabolytes, NO, endothelin

large circulating immune complexes give this appearance microscopically

wire loops - can't evenly distribute on basement membrane

streptococcal antigens appearance

planted - formed in place | subepithelial location

poststreptococcal eglomerulonephritis (abs against what?)

streptococcal exotoxin B streptococcal GAPDH endostroptosin

subepithelial humps inimmunofluorescence (suggest what?)

post-streptococcal glomerulonephritis

anti-GMB immunofluorescence pattern

linear pattern on GMB

4 stains and their uses in glomerulonephropathy

Hematoxylin & eosin (routine) Jones methenamine silver (basement membranes) periodic acid schiff (PAS) (cellular cytoplasmic inclusions) trichrome (collagen)

pANCA cANCA (associations)

pANCA - microscopic polyangiitis or Churg-Strauss cANCA - Wegener's

AGE

advanced glycolation end-products seen in diabetic/metabolic glomerular injury leads to ROS, podocyte injury, apoptosis

AOPP

advanced oxidation protein products seen in diabetic/metabolic glomerular injury leads to ROS, podocyte injury, apoptosis

flea-bitten kidney

small vessel ruptures over kidney (htn)

scotomas

spots before eyes (htn)

% children's glomerular disease primary | % adults' glomerular disease primary

95% children | 60% adults

onion-skin-like appearance

hyperplastic artherosclerosis | seen in malignant htn