medical kidney Flashcards
Define uremia, azotemia, nephritic syndrome, nephrotic syndrome, rapidly progressive glomerulonephritis
Azotemia: elevation in BUN and Cr levels, due to a decreased glomerular filtration rate (can be pre-, renal, post-) i.e. failure of excretory functions
Uremia: azotemia with signs/symptoms and biochemical abnormalities. Not only failure of excretory functions but metabolic and endocrine alterations (eg. Uremic gastroenteritis, uremic fibrinous pericarditis)
Nephritic syndrome: due to glomerular disease, acute onset hematuria, mild proteinuria, HTN
Rapidly progressive glomerulonephritis: nephritic syndrome with rapid decline (hrs to days) in GFR Nephrotic syndrome: heavy proteinuria (>3.5 g/day), hypoalbuminemia, severe edema, hyperlipidemia, lipiduria
Name and define 5 clinical manifestations of renal disease
Asymptomatic hematuria/proteinuria: mild glomerular dysfunction
Acute renal failure: oliguria/anuria, recent azotemia. Can be caused by injury to any of the 4 compartments.
Chronic renal failure: prolonged uremia, end result of all kidney diseases
Renal tubular defects: polyuria, nocturia, electrolyte disorders. Inherited or acquired.
Urinary tract infection: bacteriuria/pyuria
Nephrolithiasis: pain, hematuria
Obstruction: secondary to lesion
Distinguish between diminished renal reserve, renal insufficiency, chronic renal failure, end-stage kidney
Diminshed renal reserve: GFR 50% of normal
Renal insufficiency: GFR 20-50% of normal, with azotemia. Often anemia, HTN. Illness can precipitate uremia.
Chronic renal failure: GFR less than 20-25% of normal. Kidneys cannot regulate volume/solutes and patients have edema, acidosis, hyperkalemia. Overt uremia can occur.
End-stage renal disease: GFR <5% of normal. Uremic.
Name 4 causes of renal papillary necrosis
- Diabetes mellitus - Urinary tract obstruction - Acute pyelonephritis - Analgesic abuse
In SLE, what would the expected immunoglobulin deposition pattern be?
- “Full house” - Granular IgA, IgG, IgM, C3 within glomeruli
What are histologic findings seen in cyclosporine and FK506 nephrotoxicity (transplant kidney pathology)?
- Tubular isometric vacuolization - Hyaline arteriopathy - Acute thrombotic microangiopathy - Normal histology
What incites damage in myeloma cast nephropathy?
- Immunoglobulin light chains
Name 4 entities that present with nephrotic syndrome:
- Minimal change disease - FSGS - Membranous glomeruolpathy - Membranoproliferative glomerulonephritis
Hemolytic-uremic syndrome can demonstrate which finding within glomeruli?
-Fibrin-platelet thrombi within glomeruli
Describe typical clinical presentation of idiopathic membranous glomerulonephritis:
- Nephrotic syndrome characterized by 3.5g protein/d, hypoalbuminemia, severe edema, hyperlipidemia, lipiduria
List findings for idopathic membranous glomerulonephritis on LM.
- Diffuse involvement (>50% glomeruli) - Diffusely thickened capillary walls - Spikes on silver stains (BM expands around immune deposits) - Tubular epithelial cells with reabsorption droplets - Foam cells in interstitium or between tubular epithelial cells
Describe idiopathic membranous glomerulonephritis findings on EM and IF.
- IF: granular IgG deposits along glomerular basement membrane (+/- C3) - EM: Subepithelial electron dense deposits
What is the typical clinical presentation of Rapidly progressive glomerulonephritis?
- Rapid and progressive loss of renal function associated with severe oliguria and nephritic syndrome
What morphologic finding corresponds to RPGN?
- Glomerular crescents in >50% glomeruli
What are the major immunopathological cataegories of crescentic glomerulonephritis?
- Type 1: anti-GBM antibody mediated - Type 2: immune-complex mediated - Type 3: pauci-immune
What are the IF findings and typical disease for each of the 3 types of RPGN?
- type 1: anti-GBM, linear IgG staining along glomerular basement membrane, seen in anti-GBM disease and Goodpasture’s - type 2: immune complex, granular Ig and C3 deposits along GBM and mesangium, seen in lupus, IGA and HSP - type 3: pauci-immune, absent Ig staining, seen in ANCA associated vasculitis (WEgeners), microscopic polyangiitis
What are IgA nephropathy findings on LM, IF, and EM?
LM: Range between normal, mesangioproliferative, proliferative, crescent, then sclerotic IF: dominent IgA deposition in mesangium, with C3 EM: mesangial/paramesangial electron dense deposits
What other diseases are considerations in the differential diagnosis of IgA nephropathy?
- Lupus: can show IgA + C1q (absent in IgA nephropathy); look for subendothelial deposits - Henoch-Schonlein pupura: same kidney findings, but arthralgia, purpura, abdominal pain caused by leukocytoclastic vasculitis of dermal/bowel vessels
What is the clinical presentation of IgA nephropathy, and what are prognostic factors?
- Presents as microscopic hematuria or intermittent gross hematuria; may also present with nephritic syndrome or renal failure - Worse prognosis with severe renal insufficiency at presentation, greater proteinuria, extensive crescent formation, extensive glomerular/tubulointerstitial scarring
What is the classification of lupus nephritis and how does it relate to prognosis?
Class1: Minimal mesangial lupus nephritis-excellent prognosis Class2: mesangial proliferative lupus-Good prognosis Class 3: Focal lupus nephritis-Good Class4: diffuse segmental/global lupus-Moderate to poor Class 5: membranous lupus-Moderate Class 6: Advanced sclerosing lupus nephritis-Poor
What are examples of active and chronic glomerular lesions?
- Active: endocapillary hypercellularity, karyorrhexis, fibrinoid necrosis, rupture of GBM, crescents (cellular/fibrocellular), subendothelial deposits by LM (wire loops), intraluminal immune aggregates (hyaline thrombi) - Chronic: glomerular sclerosis, fibrous adhesions, fibrous crescents
Renal transplant bx: What are the adequacy criteria?
- At least 10 glomeruli and 2 muscular-walled small arteries for LM - one glomerulus for IF, one for EM
How is transplant rejection classified?
- Temporally: hyperacute, acute, chronic - By mechanism: cellular, humoral
Outline the Banff classification scheme for reporting renal transplant biopsies.
- Class 1: normal - Class 2: antibody-mediated rejection - Class 3: borderline changes, suspicious for acute cellular rejection - Class 4: T-cell mediated rejection - Class 5: interstitial fibrosis and tubular atrophy - Class 6: other changes not related to rejection
What are the histologic features of acute cellular rejection?
- interstitial mononuclear inflammator infiltrate - tubulitis - intimal arteritis - vasculitis with fibrinoid necrosis - glomerulitis
What are the features of acute antibody-mediated rejection?
- LM: ATN-like with minimal inflammation, capillaritis, vasculitis - IF: C4d staining in peritubular capillaries - presence of circulating anti-donor antibodies
Name medications associated with changes to renal/urinary tract and describe change
Cyclosporine: - acute nephrotoxicity: acute tubular injury, isometric tubular cell vacuolization - arteriolopathy: smooth muscle cell degeneration, necrosis, loss of myocytes, hyaline deposists - thrombotic microangiopathy - chronic nephrotoxicity with patchy tubular arophy and interstitial fibrosis NSAIDS: - hemodynamically induced acute renal failure, decreased synthesis of vasodilatory prostaglandins - Acute hypersensitivity interstitial nephritis - Acute interstitial nephritis+minimal change - Membranous nephropathy phenacetin: chronic tubulointerstitial nephritis, renal papillary necrosis
What is the typical presentation of RPGN? What morphologic finding corresponds to RPGN?
- rapid and progressive loss of renal function associated with severe oliguria and nephritic syndrome - glomerular crescents in >50% of glomeruli
List 4 lesions associated with plasma cell dyscrasias
- Myeloma - Monoclonal immunoglobulin deposition disease - amyloidosis - fibrillary glomerulonephritis - immunotactoid glomerulopathy - bence-jones cast nephropathy
Define a Bence-Jones protein
- Monoclonal light chain found in urine/blood
What are 2 mechanisms by which Bence-Jones proteins cause renal damage?
- Light chains are directly toxic to epithelial cells
- Bence jones proteins combine with urinary glycoprotein (Tamm-Horsfall) to form tubular casts that obstruct tubular lumens and induce inflammatory reaction around the casts
List the LM, IF and EM findings for the plasma cell dyscrasia-associated kidney lesions
- Myeloma cast nephropathy:
- LM: large brittle casts w/ fracture lines, PAS neg, eosinophilic on trichrome, maybe congo red+
- IF: monoclonal light chain in casts
- EM: cast is deeply electron dene
- Monoclonal Ig deposition disease:
- LM: nodular glomerulopathy, mesangial expansion, widened tubular basement membranes
- IF: Monoclonal Ig bound to all basement membranes
- EM: clustered, punctate dense deposits next to tubular BM and in glomerular/vascular BM
- Amyloidosis:
- Amorphous, pale eosinophilic material in mesangium, capillary wll, arterioles, congo red +
- IF: AL amyloid + for light chain Ig
- EM: randomly arranged fibrils, 10-12 nm in arterioles, arteries, mesangium, interstitium
- Fibrillary glomerulonephritis:
- Increase in mesangial cellularity and irregularly thickened capillary walls, congo red -
- IF: coares linear/confluent IgG, C3, one or both light chains
- EM: fibrils, 10-20nm throughout mesangium/basement membrane
- Immunotactoid glomerulopathy:
- Membranoproliferative glomerulonephritis type 1
- IF: granular capillary IgG, complement, one or both light chains
- EM: corase, hollow fibrils 20-80 nm
List the ddx of diabetic nephropathy for the glomerular changes
- Mesangioproliferative glomerulonephritis
- Monoclonal immunoglobulin deposition disease
- IgA nephropathy
- Lupus nephritis
List 2 findings of diabetic nephropathy on EM
- Thickened glomerular basement membrane due to protein insudation
- Mesangial matrix expansion
List 2 non-glomerular findings in diabetic kidney
- Renal vascular lesions including renal atherosclerosis and arteriolosclerosis
- Pyelonephritis: acute/chronic pyelonephritis common in diabetics
***papillary necrosis is more common***
List 4 glomerular lesions seen in diabetes
- Capillary basement membrane thickening
- Diffuse mesangial sclerosis (PAS+)
- nodular glomerular sclerosis aka Kimmelstein-Wilson nodules, PAS+ in periphery surrounded by patent capillaries
- accumulation of hyaline material “fibrin caps” on capillary loops, and capsular drops when adherant to Bowman’s capsule
Briefly describe how sections of kidney are prepared for EM
- fixation in glutaraldehyde
- impregnation with osmium tetroxide
- embed tissue in epoxy resin
- cut semi-thin 1 um section and stain with toluidine blue
- select area for scoping; cut thin section
- double-stain with uranyl acetate/lead citrate on copper wire
Minimal change nephropathy
- most common cause of idiopathic nephrotic syndrome in children
- usually <6 yrs, males, caucasians
- often preceding viral illness/vaccine/allergy/drug exposure, possibly ass. with hodgkins
- thought to be T lymphocyte related damage to podocytes
- presents with heavy selective proteinuria
- complete remission after 8 weeks with steroids
- LM: normal glomerulus, convoluted tubules are vacuolated due to lipid
- IF: neg, albumen in tubules
- EM: total foot process effacement, distortion of filtration slits, visceral epithelial cells wtih many organelles and cysts
Name 10 glomerular lesions associated with nephrotic syndrome
- Minimal change
- FSGS
- C1q nephropathy (C1q deposits in mesangium)
- Membranous glomerulonephritis (uniform capillary wall thickening, spikes are subepithelial, IgG and C3 along capillary wall)
- Diabetic nephropathy (nodular/diffuse mesnagial sclerosis, GBM thickening, linear IgG along capillary walls)
- Amyloidosis
- Light chain deposition disease
- Heavy chain deposition disease
- Fibrillary glomerulonephritis
- Imuunotactoid glomerulopathy
- COngenital neprhotic syndrome (Finnish type, diffuse mesangial sclerosis or Denys Drash)
FSGS: list come features
- presents with proteinuria, high incidence of renal failure (ESRD in 10-20 yrs)
- sclerosis from increase in mesangial matrix obliterating glomerular capillaries
- variants include tip lesion, perihilar lesion, cellular variant, collapsing variant and NOS
- african americans, 10% in kids, 20-30% of nephrotic syndrome in adults, in 3-4 decade
- segmental sclerosis involving one or more lobules of glomerular tuft near axial region, adhering to bowmans capsule
- areas of tubular atrophy common, with interstitial fibrosis
- EM: extensive foot process effacement, not only in sclerosed areas. Visible increase in mesangial matrix. Hyaline deposits, BM thickening/folding.
IF: IgM and C3 subendothelial in sclerosed areas
What are some secondary causes of FSGS?
- Familial (mutations in nephrin, podocin, WT1…)
- Viral (HIV, parvovirus B19, CMV, SV40, EBV)
- Drugs (heroin, Interferon alpha, lithium)
- “adaptive functional response” unilateral renal agenesis, reflux nephropathy, partial cortical necrosis, surgical ablation, morbid obesity, HTN, sickle cell
If you have collapsing glomerulopathy, what do you expect to see and what are the causes?
- Distinct variant of FSGS, characterized by widespread collapse of glomerular capillary loops, poor prognosis
- ass. with IV drug abuse, HIV, HCV and some autoimmune
- will see segmental, global hypertrophy and hyperplasia of epithelial cells overlying sclerotic segment, cells are swollen and vacuolated with many resorption droplets. Tubulointerstiial injury is severe.
- IF: IgM and C3
- EM: tubuloreticular inclusions on top of podocyte effacement
Fibrillary and immunotactoid glomerulopathies: describe
- 2 rare variants of glomerolopathy defined by EM
- Extracellular deposition of non-branching, randomly arrayed fibrils aproximately 20 nm (fibrillary) and 20-50nm in parallel/stacked arrays (immunotactoid)
- Negative for Congo Red/Thioflavin T
- Fibrillary is more common, middle aged African Americans, heavy proteinuria, ESRD within 2 yrs
- LM for both: mesangial hypercellularity, thickening of glomerular capillarly walls, mesangial expansion with amorphous PAS+ material. Crescents are possible.
- EM deposits in all compartments; foot process effacement
- IF: IgG and C3 in all compartments
Light-chain and Heavy-chain deposition diseases: give a few featurs
- LCCDD: overproduction and extracellular deposition of monoclonal immunoglobulin light chain; can have cardiac/hepatic/neural changes
- Much in common with AL amyloid, but granular, Congo Red negative, and usually Kappa light chain.
- Heavy proteinuria, ESRD
- GLomeruli enlarged, PAS+ material causing capillary wall thickening, nodular expansion of mesangium
- EM: continuous deposition of electron-denes material in GBM, mesnagium and along tubular basement menbranes. It is finely granular!
**HCDD: ** systemic deposition of monoclonal Ig heavy chain; due to deletion in first common domain (CH1) to make it secretable by plasma cells
- Presents with hypocomplement, otherwise similar to LCDDD
- Looks like LCDDD on LM/EM
- IF: gamma heavy chains+, neg for both kappa/lambda
Fabry’s disease: list some features
- uncommon x-linked disorder
- deficiency of alpha-galactosidase A
- accumulations of neutral lycosphingolipid Gb3 in kidneys, heart, neurons, blood vessels
- present with many angiokeratomas, paresthesias, hypophydrosis, corneal opacities; death in 4th-5th decade
- LM: visceral epithelial cells are enlarged and vacuolated giving honeycomb appearnace; similar change in Bowman’s epithelium, endothelial and mesangial cells. Vacuoles are PAS neg.
- EM: massive accumulation of laminated inclusion bodies (zebra bodies) with concentric myelin-like structure; also in endothelial/tubule cells.
