Renal Path Flashcards
nephrotic syndrome
massive proteinuria with hypoalbuminemia, resulting edema, hyperlipidemia, frothy urine with fatty casts
minimal change disease
most common cause of nephrotic syndrome in children
often primary and may be triggered by recent infection, immunization, immune stimulus,
- rarely secondary to lymphoma (cytokine-mediated damage)
minimal change disease LM
normal glomeruli (lipid may beseen in PCT cells)
minimal change disease IF
negatve
minimal change disease on EM
effacement of podocyte foot processes
focal segmental glomerulosclerosis
most common cause of nephrotic syndrome in African Americans and Hispanics
can be primary or secondary to other conditions (HIV, sickle, IVDA, obesity, IFN tx, or congenital malformations)
FSGS LM
segmental sclerosis and hyalinosis
FSGS IF
often negative, but may be positive for nonspecifci focal deposits of IgM, C3, C1
FSGS EM
effacement of foot processes similar to minimal change disease
membranous nephropathy
aka membranous glomerulonephritis
can be primary (antibodies to phospholipase A2R) or secondary to drugs (NSAIDs, penicillamine, gold), infections (HBV, HCV, syphilis), SLE, or solid tumors
membranous nephropathy LM
diffuse capillary and GBM thickening
membranous nephropathy IF
granular due to IC deposition
membranous nephropathy
‘spike and dome’ appearance of sub epithelial deposits
membranous nephropathy tx
primary disease has poor response to steroids
may progress to CKD
amyloidosis
kidney is most commonly involved organ (systemic amyloidosis)
assoc with chronic conditions that predispose to amyloid deposition (AL amyloid, AA amyloid)
amyloidosis LM
Congo red stain shows up apple-green birefringence under polarized light due to amyloid deposition in the mesangium
diabetic glomerulonephropathy
most common cause of ESRD in the US
how are kidneys affected in diabetes
hyperglycemia -> nonenzymatic glycation of tissue proteins -> mesangial expansion
GBM thickening and increase permeability
hyperfiltration (glomerular HTN and increase GFR) -> glomerular hypertrophy and glomerular scarring (glomerulosclerosis) leading to further progression of nephropathy
diabetic glomerulonephropathy LM
mesangial expansion, GBM thickening, eosinophilic nodular glomerulosclerosis
Kimmelstiel-Wilson lesions
nephritic syndrome
inflammatory process
glomeruli involvement -> hematuria and RBC casts in urine
associated with azotemia, oliguria, hypertension (due to salt retention), proteinuria, hypercellular/inflamed glomeruli on biopsy
acute poststreptococcal glomerulonephritis
most frequently seen in children ~2-4wks after Group A strep infection of pharynx or skin
acute post streptococcal glomerulonephritis prognosis
resolves spontaneously in children, may progress to renal insufficiency in adults
acute post-streptococcal glomerulonephritis immunology
type III hypersensitivity reaction
presentation of acute post-streptococcal glomerulonephritis
presents with peripheral and periorbital edema, cola-colored urine, HTN
+ strep titers/serologies
decrease complement (C3) levels d/t consumption
post-streptococcal glomerulonephritis LM
glomeruli enlarged and hypercellular
post-streptococcal glomerulonephritis IF
‘starry sky’ granular appearance (‘lumpy bumpy’) due to IgG, IgM, and C3 deposition along GBM and mesangium
post-streptococcal glomerulonephritis EM
sub epithelial immune complex humps
rapidly progressive (crescentic) glomerulonephritis
rapidly deteriorating renal function (days to weeks)
rapidly progressive (crescentic) glomerulonephritis LM
crescent moon shaped
- crescents consist of fibrin and plasma proteins (C3b) with glomerular parietal cells, monocytes, macrophages
rapidly progressive (crescentic) glomerulonephritis - goodpasture syndrome IF
linear IF due to antibodies to GBM and alveolar basement membrane
good pasture syndrome
hematuria/hemoptysis
type II hypersensitivity reaction
tx: plasmapheresis
rapidly progressive (crescentic) glomerulonephritis - Wegener’s IF
negative IF/Pauci-immune (no Ig/C3 deposition)
PR3-ANCA (c-ANCA)
rapidly progressive (crescentic) glomerulonephritis - microscopic polyangiitis IF
negative IF/Pauci-Immune (no Ig/C3 deposition)
MPO-ANCA/p-ANCA
rapidly progressive (crescentic) glomerulonephritis - PSGN or DPGN
granular IF
diffuse proliferative glomerulonephritis
often d/t SLE (think ‘wire lupus’)
DPGN and MPGN often present as nephrotic syndrome and nephritic syndrome concurrently
diffuse proliferate glomerulonephritis LM
‘wire looping’ of capillaries
diffuse proliferative glomerulonephritis IF
granula
diffuse proliferative glomerulonephritis EM
subendothelial and sometimes intramembranous IgG-based ICs often with C3 deposition
IgA nephropathy
episodic hematuria that occurs concurrently with respiratory OR GI tract infections (IgA is secreted by mucosal linings)
renal pathology of IgA vasculitis (HSP)
IgA nephropathy LM
mesangial proliferation
IgA nephropathy IF
IgA-based IC deposits in mesangium
IgA nephropathy EM
mesangial IC deposition
Alport syndrome
mutation in type IV collagen -> thinning and splitting of glomerular basement membrane
X-linked dominant
Alport syndrome presentation
Eye problems (retinopathy, lens dislocation), glomerulonephritis, sensorineural deafness 'can't see, can't pee, can't hear a bee'
alport syndrome EM
basket-weave
membranoproliferative glomerulonephritis
nephritic syndrome that often co-presents with nephrotic syndrome
type I membranoproliferative glomerulonephritis
may be secondary to hepatitis B or C infection
may also be idiopathic
sub-endothelial IC deposits with granular IF
type II membranoproliferative glomerulonephritis
associated with C3 nephritic factor (IgG antibody that stabilizes C3 convertase -> persistent complement activation -> decrease C3 levels)
intramembranous deposits, aka dense deposit disease
membranoproliferative glomerulonephritis
mesangial ingrowth -> GBM splitting -> ‘tram-track’ appearance on H&E and PAS stains
casts
indicates that hematuria/pyuria is of glomerular or renal tubular origin
bladder cancer, kidney stones -> hematuria, no casts
acute cystitis -> pyuria, no casts
RBC casts
glomerulonephritis, hypertensive emergency
WBC casts
tubulointerstitial inflammation, acute pyelonephritis, transplant rejection
fatty casts (‘oval fat bodies’)
nephrotic syndrome
associated with ‘Maltese cross’ signs
granular (‘muddy brown’) casts
acute tubular necrosis (ATN)
waxy casts
end-stage renal disease/chronic renal failure
hyaline casts
nonspecific, can be a normal finding, often seen in concentrated urine simplex
Acute interstitial nephritis causes
drugs act as happens, inducing hypersensitivity (diuretics, penicillin derivatives, proton pump inhibitors, sulfonamides, rifampin, NSAIDs)
less commonly secondary to other processes such as systemic infections (Mycoplasma) or autoimmune (Sjogren, SLE, sarcoidosis)
acute interstitial nephritis findings
pyuria (classically eosinophils) and azotemia
fever, rash, hematuria, pyuria, and CVA tenderness, but an be asymptomatic
AIN mnemonic
P's: Pee (diuretics) Pain-free (NSAIDs) Penicillins and cephalosporins Proton pump inhibitors rifamPin
acute tubular necrosis causes
ischemic or nephrotoxic
ischemic ATN
secondary to decrease renal blood flow (hypotension, shock, sepsis, hemorrhage, HF)
-> death of renal tubular cells that may slough into tubular lumen
(PCT and thick ascending limb are highly susceptible to injury)
nephrotoxic ATN
secondary to injury resulting from toxic substances (ahminoglycosides, radio contrast agents, lead, cisplatin, ethylene glycol), crush injury (myoglobulinuria), hemoglobinuria
proximal tubules are particularly susceptible to injury
stages of ATN
- inciting event
- maintenance phase - oliguric; lasts 1-3wks; risk of hyperkalemia, metabolic acidosis, uremia
- recovery phase - pyloric; BUN and serum creatinine fall; risk of hypokalemia and renal wasting of other electrolytes and minerals
key finding of ATN
granular (muddy brown) casts
distal renal tubular acidosis (type 1) defect
inability of α-intercalated cells to secrete H+ -> no new HCO3- is generated -> metabolic acidosis
RTA type 1 urine pH
> 5.5
RTA type 1 serum K+
decrease
RTA type 1 causes
amphotericin B toxicity, analgesic nephropathy, congenital anomalies (obstruction) of urinary tract, autoimmune diseases (SLE)
RTA type 1 associations
increase risk of calcium phosphate kidney stones (due to increase urine pH and increase bone turnover)
proximal renal tubular acidosis (type 2) defect
defect in PCT HCO3- reabsorption -> increase excretion of HCO3- in urine -> metabolic acidosis
urine can be acidified by α-intercalated cells in collecting duct, but not enough to overcome the increased excretion of HCO3- -> metabolic acidosis
RTA type 2 urine pH
< 5.5
RTA type 2 serum K+
decrease
RTA type 2 causes
Fanconi syndrome, multiple myeloma, carbonic anhydrase inhibitors
RTA type 2 associations
increase risk for hypophosphatemic rickets (in Fanconi syndrome)
hyperkalemic tubular acidosis (type 4) defects
hypoaldosteronism or aldosterone resistance; hyperkalemia -> decrease NH3 synthesis in PCT -> decrease NH4+ excretion
RTA type 4 urine pH
< 5.5 (or variable)
RTA type 4 serum K+
increase
RTA type 4 causes
decrease aldosterone production (e.g. diabetic hyporeninism, ACEi, ARBs, NSAIDs, heparin, cyclosporine, adrenal insufficiency) or aldosterone resistance (e.g. K+-sparing diuretics, nephropathy due to obstruction, TMP-SMX)
