renal pathology Flashcards
what is the leading cause of kidney failure
2nd leading cause
diabetes and HTN
renal cortex is responsible for
all filtration
most disease in kidney is focused in
glomeruli
what portion of the kidney is most sensitive to ischemia?
cortex
what portion of the medulla is thick ascending limbs, thick and thin descending limbs and collecting ducts?
outer
what portion of the medulla is thin limbs of loop of Henle and distal collecting ducts?
inner
what effect on permeability of glomerular capillary wall does increasing negative charge have?
decrease
are diaphragms present in fenestrated endothelium pores?
no
what is the podocyte membran protein found in podocyte slit diaphragms?
nephrin
what makes up the glomerulus filtration barrier
endothelium,
basement membrane, and layer
of podocyte foot processes.
inflammation of kidney blood vessels seen in which conditions
systemic vasculitis,
transplant rejection
what glomerular histologic alteration is more than 3 nuclei/mesangial area
“Endocapillary” proliferation: endothelial, mesangial, leukocyte
Visceral epithelial proliferation
Parietal epithelial proliferation (“crescent”)
Leukocytic infiltration
hypercellularity
T/F: patients w diabetes have a lot of endocapillary hypercellularity of mesangium
false- they have a lot of extracellular matrix material that expands that area
T/F: patients w proliferative glomerulonephritis have hypercellularity w lots of neutrophils and lymphocytes
true … kids w post-strep infection also can get this, where they have a cross reactive antigen that deposits w/in the GBM starting an immune process
what glomerular histologic alteration can result from Protein deposits: immune complex, organized deposits (polymers)?
mesangium
what indicates severe glomerular injury?
is proliferative lesion, composed of epithelial and/or inflammatory cells, collagen and fibrin, and results in partial filling of Bowman’s space?
crescents
what changes can you have in GBM
thickening
mesangial cell inerpositioning
heterlogous protein deposition
thinning/splitting
what is term for nuclear fragmentation resulting in necrosis?
karyorrhexis
what is glomerular hyalinosis
deposition of serum proteins
homogenous eosinophilic appearance
global glomerular lesions affect
entirety of individual glomeruli
segmental glomerular lesions affects
portion of individual glomeruli
diffuse glomerular lesions affects
all glomeruli
focal glomerular lesions affects
some but not all
3 phases of immune complex disease
complex formation
deposition of tissues
activation of inflammatory response
anti GBM disease antibodies directed against
type 4 collagen
IF of anti GBM disease
linear deposition of Ig along GBM
goodpastures syndrome has
anti GBM antibody
renal disease
pulmonary disease
subepithelial deposits fo GBM are associated with
“humps” near the outer GBM… these can make it hard to see foot processes
how do immune complexes activate neutrophils and macrophages
by by cross-linking Fc receptors: induces mediator release Proinflammatory cytokines Prostaglandins Chemotactic molecules Lysosomal proteases
what complex involved in complement cascade via C1 complex consists of C5-9 (cell lysis)?
MAC (membrane attack complex)
what components of the complement cascade are Anaphylatoxins that cause vascular permeability?
C3a
C5a
what component of the complement cascasde is a Chemotactic products leukocyte migration?
C5a
in diabetes, what hormone can cause Glomerular hyperfiltration, which can lead to Glomerular Hypertension, and Hypertrophy of GBM?
ANP (atrial natriuretic peptide)
when do you get non-immunologic compensatory hyperfiltration injury?
- occurs when 50-70% nephron mass lost
- endothelial and epithelial injury of glomeruli
- glomeruli capillary hypertension
all these problems lead to focal segmental GS and proteinuria
what is alports syndrome
Thinning, splitting, and basket weaving of glomerular BM b/c cant form type 4 collagen\
Also go deaf
if you damage glomeruli you also damage
tubules
clinical signs of acute glomerulonephritis
- Hematuria (blood in urine),
- hypertension
- Azotemia (increased BUN & nitrate products in body)
- oliguria (not peeing as much)
- edema, proteinuria - variable
etiologies of acute glomerulonephritis
- post infectious GN (post-strep)
- primary glomerular disease -> IgA nephropathy, MPGN
- multi system diseases -> lupus, vasculitides
rapidly progressing glomerulonephritis will appear clinically as
acute nephritis,
rapid progression to ARF
think crescents
pathology of rapidly progressing glomerulonephritis
Crescentic Glomerulonephritis-> proliferation of parietal epithelial cells forming a layer >2 cells thick… also will see endocapillary proliferation
pathogenesis of rapidly progressing glomerulonephritis
- there will be severe glomerular, antibody-mediated injury
- can be lupus (most common), also can be IgA, anti-GBM, etc
what defines nephrotic syndrome
- proteinuria > 3.5 g/24 hours (usually they have damage to podocytes which causes this)
- edema
- hyperlipidemia, lipiduria
- hypoalbuminemia (the moment GBM is damaged, albumin gets thru- this tells u kidney is damaged)
pathogenesis of nephrotic syndrome
glomerular injury resulting in altered capillary permeability and loss of barrier function w passage of proteins
The moment the GBM is damaged, _______ starts getting thru… this tells u kidney is damaged and can be a sign before the damage gets really bad. Check this in diabetics
albumin
what defines nephritic syndrom
hematuria decreased urine output oliguria elevated BUN & creatine HTN proteinuria, edema
causes of nephritic syndrom
Acute post infections glonerulonephritis
IgA nephropathy
Systemic lupus erythematous
proteinuria greater than ____ mg/day is abnormal
150mg/day… this could be from a glomerular defect in filtration function of capillary wall, or tubular failure of reabsorption (small proteins usually reabsorbed here)
how do u test for proteinuria
- “dip stick” – detects urine albumin, but not IgL
- Sulfosalicylic acid preparation – detects all proteins
what causes the complication of accelerated atherosclerosis in nephrotic syndrome
hyperlipidemia
what is the nephrotic syndrome complication is due to hyperfibrinogenemia & loss of AT III, can lead to Renal vein thrombosis
Pulmonary embolism?
hypercoagulation
what type of anemia, due to loss of transferrin, can result as a complication of nephrotic syndrome?
hypochronic microcytic
what pathology resulting from a complication of nephrotic syndrome results from loss of Ig?
infection
what pathology resulting from a complication of nephrotic syndrome results from loss of cholecalciferol binding protein?
hypercalcemia
what pathology resulting from a complication of nephrotic syndrome results from loss of thyroxine binding globulin?
hypothyroidism
etiologies of nephrotic syndrome from primary glomerular lesions
- minimal change disease
- focal segmental glomerulosclerosis
- membranous glomerulopathy
- membranoproliferative glomerulopathy (often nephritic)
- IgA nephropathy (often nephritic)
etiologies of nephrotic syndrome from systemic diseases
- diabetes
- SLE
- amyloidosis
what disease accounts for over half of the nephrotic syndrome cases in kids?
minimal change disease… peak age is 2-6 yrs old
clinical features of minimal change disease
proteinuria highly selective for albumin
how do u detect MCD
nothing shows up on light microscopy or IF!
you will see extreme podocyte damage on electron microscopy!!
most kidney problems start with ____________ that pisses off immune system leading to kidney dis
upper respiratory infection
clinical features of FSGS (focal segmented glomerulosclerosis)
- proteinuria (may or may not be in nephrotic range)
- hematuria v common
- *normal renal function early, but later progressive loss of function (e.g. creatinine begins to rise)
- hypertension
- affects both children & adults, M>F
FSGS much higher incidence in
african americans
histo of FSGS
- focal, segmental, global glomerulosclerosis
- segmental sclerosis of any glomeruli is abnormal and indicates glomerular injury
- global sclerosis of small numbers of glomeruli is normal (when this becomes >10% u have a problem)
FSGS pathogenesis
- decreased renal mass can lead to this
- morbid obesity- causes kidneys to work harder
- chronic pyelonephritis - more common in women except in older men when prostate clamps bladder
what is collapsing glomerulopathy
Worse variant of FSGS related to HIV or idiopathic. Fastest developing and leading to kidney failure.
clinical signs of collapsing glomerulopathy
- massive proteinuria
- rapid progression to renal failure
- poor response to therapy
pathogenesis of membranous glomerulopathy (MGN)
immune complex deposition
etiologies of membranous glomerulopathy (MGN)
- autoantibody against glomerular epithelial cell antigens (idiopathic)
- happens secondary to: malignancy, SLE (called membranous lupus nephritis), and infection
you see spikes and holes in jones silver stain w which dis
membranous glomerulopathy (MGN)
clinical presentation of MGN
- nonselective proteinuria, usually nephrotic
- hematuria common
- hypertension rare
what do u see on IF of MGN
granular IgG and C3 along capillary wall
what kind of deposits are in MGN
subepithelial
immune complex mediated MPGN is characterized by
cellular proliferation and thickening of capillary walls
MPGN type I (most common) presentation:
- proteinuria (usually nephrotic, but may be mild)
- hematuria
- hypocomplementemia (low serum C3 levels)
pathology of glomeruli in type I MPGN
- hypercellularity-> mesangial and infiltrating mononuclear cells in global distribution
- thick walled capillary loops ->double contour or tram-track appearance of GBM (seen on silver)
ultrastructure of MPGN type I
electron dense, immune deposits in subendothelial and mesangial locations… new BM material laid down by endothelial cells over deposits & cells
IF of type I MPGN
granular C3 along the GBM at the periphery of the lobules (w central sparing), mesangial deposits may be present also
MPGN type I etiology
- immune complex pathogenesis -> activated by complement
- also can happen secondary to systemic illness: SLE, Hep C
what happens in MPGN type II: Dense Deposit Disease
Autoimmune dis (aka C3 nephritic factor) directed at C3bBb (C3 convertase). Antibody stabilizes the enzymes, prevents its degradation, leads to increased complement activation and consumption
IF of MPGN type II
smooth, ribbon-like deposits of C3 along glomerular capillary wall (pseudolinear)
clinical course of type 1 MPGN
Persistent or intermittent Nephrotic Syndrome
Gradual progression to renal failure (30-50%)
Prognosis worsens with nephrotic proteinuria
clinical course of type 2 MPGN
Progresses to renal failure in most cases
Frequently recurs in transplanted kidneys
diabetic glomerulosclerosis accounts for __% of deaths in pts <40yrs
20
diabetic glomerulosclerosis histo:
- nodular glomerulosclerosis–> Kimmelstiel-Wilson disease
- small vessels (arterioles) damaged before arteries in diabetes
- PAS & silver positive
you see nodular glomerulosclerosis on histo in which diseases
- diabetes
- amyloid
- light chain
- MPGN
capsular drop/fibrin cap is damage that can occur to bowman’s capsule from
diabetes
diabetic glomerulosclerosis EM
- diffuse uniform thickening of GBM
- mesangial matrix expansion
what are deposition disorders
Diverse group of diseases characterized by deposits of protein often in ultrastructurally organized forms
immunoglobulin derived deposition disorders
amyloidis and cryoglobuinemia
what amyloid protein seen in amyloidosis is associated with plasma cell dyscrasias (e.g. multiple myeloma), composed of monoclonal light chain fragments (usually lambda light chains)?
AL (primary)
what amyloid protein seen in amyloidosis is associated with chronic disease
derived from serum amyloid A protein by proteolytic cleavage and polymerization?
AA (secondary)
amyloidis presenting features
renal disease with proteinuria often nephrotic, reduced renal function, rarely HTN
what stains amyloidis
congo red
what is cryoglobulins
serum proteins that precipitate upon cooling
cryoglobulinemia associated with
HCV hep c
cryoglobulinemia associated with
Raynaud’s phenomenon Vasculitis Arthralgias Purpura Hypocomplementemia: reduced C1, C4, but elevated C3
cryoglobulinemia appears
usually appears years after systemic onset:
Hematuria in almost all cases
Proteinuria, +/- nephrotic syndrome (20%)
Acute renal failure
cryoglobulinemia looks like
MPGN
Hypercellular, lobulated glomeruli with “double contours”
Capillary loop ‘pseudothrombi’ (cryoglobulin deposits)
whta type of deposits in cryoglobulinemia
Large subendothelial deposits composed of distinctive annular or tubular structures
types of congenital nephrotic syndromes
finnish type
diffuse mesangial sclerosis
congenital syphilis
clinical features of acute post-infectious glomerulonephritis
- ** anti strepolysin O
- acute nephritis -> oliguria, periorbital edema, hypertension, smokey urine
- decreased C3 (returns to normal w/in 2 wks)
- pathogenesis occurs 2 wks after infection
IF of acute post-infectious glomerulonephritis
coarse granular deposits of IgG and C3
what is the most common primary glomerulonephritis
IgA Nephropathy (Berger’s dis) -
peak age is 15-30 yrs old
M>F
presenting feature of IgA nephropathy
asymptomatic hematuria … this is usually a very slow progressive dis
pathogenesis of IgA nephropathy
IgA immune complexes are abnormal, so it cannot be degraded in liver.
etiologies of IgA nephropathy
Chronic liver disease,
Crohn’s dis,
gluten enteropathy,
chronic bronchitis
IF of IgA nephropathy
mesangial granular IgA
serology of lupus-
anti-nuclear Abs, decreased C3
when patients w/SLE have anti-phospholipid Abs
predisposed to thrombosis (DVT),
predisposed to repeated miscarriages
full house staining is seen in
SLE
deposits everywhere, subendo and mesangial
C1q deposits only really seen in
lupus
rapidly progressive glomerulonephritis RPGN characterized by
rapid loss of renal function (acute renal failure)… typically associated with glomerular crescent formation. Creatinine will skyrocket quickly.
IF of anti-GBM dis
continuous linear IgG along capillary walls
what is ANCA
‘anti-neutrophil cytoplasmic antibodies’ are antibodies directed against neutrophil granule contents
Wegner granulomatosis usually affects
upper/lower respiratory tracts, M>F, age 40
Wegner granulomatosis looks like ___
anti GBM but they have negative IF not linear
prerenal causes of acute kidney failure
Due to hypoperfusion (blood isn’t getting to kidney which is causing damage). Often caused by trauma
postrenal cause of acute kidney failure
urinary tract obstruction
intrarenal causes of acute kidney failure
due to disease of renal parenchyma:
- glomerular: RPGN
- vascular: vasculitis, thrombosis, thrombotic microangiopathies
- acute tubular necrosis, acute tubulointerstitial nephritis, myeloma cast nephropathy
acute tubular necrosis is the most common cause of
ARF
clinical features of acute tubular necrosis
acute decline GFR
oliguria/anuria
rising BUN and creatine
what is the major cause of acute tubular necrosis
ischemia
- also can be caused by toxicity from antibiotics and radio-contrast agents
what makes kidneys susceptible to acute tubular necrosis?
- they receive 25% of cardiac output
- substances are concentrated in tubules of kidneys
- have a lot of mitochondria/need a lot of oxygen
histo of acute tubular necrosis
- proximal tubular dilation and flattening of epithelium
- granular casts in distal tubules
which antibiotics can cause acute tubular necrosis
aminoglycosides,
amphotericin B
acute tubulointerstitial nephritis clinical features
acute renal failure -> increased BUN and creatinine
- symptoms occur 2 wks after drug was started, if stopped can get full recovery
what are causative agents of acute tubulointerstitial nephritis
antibiotics, diuretics, anticonvulsants, non steroidal and non inflammatory and antacids
which antibiotics cause acute tubulointerstitial nephritis
penicillins and cephalosporins
histo of acute tubulointerstitial nephritis
inflammation in interstitium
infiltrating cells: eosinophils!!!
inflammation in tubulues with or without necrosis
acute tubulointerstitial nephritis subtypes?
analgesic and NSAID nephropathys
analgesic nephropathy increased risk for
transitional cell carcinoma
NSAID nephropathy
cyclooxyygenase inhibitors mess w kidney’s ability to maintain BP
Myeloma cast nephropathy - clinical features?
acute or chronic renal failure,
proteinuria- not detected on dip stick
pathology of myeloma cast nephropathy
eosinophil casts,
fractured casts- they’re hard as rocks so crack when u cut thru them for staining,
these casts have a 2-toned look- easy to spot,
tubular epithelial damage or necrosis
what is unusual about IF of myeloma cast nephropathy
Only one light chain isotope shows up- usually kappa, or lambda. In normal patients these would have equal staining
vascular diseases of kidney
Benign Nephrosclerosis Malignant Nephrosclerosis Systemic Sclerosis Thrombotic Microangiopathies Vasculitides
what is renal disease in benign HTN
benign nephrosclerosis
clinical features of benign nephrosclerosis
proteinuria and or slow progression to renal failure
renal disease in malignant HTN
Malignant nephrosclerosis
“onion skinning” hyperplastic arteriolosclerosis
Malignant nephrosclerosis
Malignant nephrosclerosis clinical features
renal failure and death if not treated immediately
hrombotic microangiopathy is a group of disorders characterized by
microthrombosis of arterioles and capillaries, which is caused by microangiopathic hemolytic anemia
reduced platelets
often with ARF
hemolytic-uremic syndrome can cause ________________, which can often lead to acute renal failure & death in 1/2 adults who get this
thrombotic microangiopathy
pathogensis of thrombotic microangiopathy
endothelial cell injury
platelet aggregation
together cause vascular obstruction
Hemolytic-Uremic syndrome clinical finidings
acute renal failure,
thrombocytopenia,
hemolytic anemia
types of renal allograft rejections
hyperacute
acute
chronic
clinical features of hyperacute rejection
anuria, fever, pain
immediate kidney removal necessary
when does acute rejection cocur
few weeks to months
clinical features of acute rejection
sudden azotemia(elevated creatine/BUN)
oliguria
sometimes fever, graft tenderness
pathology of acute cellular rejection to kidney transplant
interstitial inflammation: lymphocytes (T cells) come in & damage organ
clinical features of chronic rejection
progressive azotemia, oliguria, HTN months to years after
chronic rejection of kidney transplant - pathology?
- intimal sclerosis/proliferation of small and large arteries, may be obliterative
- not responsive to therapy
primary diseases most likely to reccur after kidney transplant?
Membranoproliferative glomerulonephritis
Anti-GBM disease
IgA nephropathy
Focal segmental sclerosis, variable
why is urinary tract obstruction important to detect?
- it’s usually easily correctible,
- often affects young children,
- results in irreversible renal damage & ultimately failure if untreate
causes of urinary tract obstruction
benign prostatic hypertrophy,
tumors,
calculi (stones,
congenital abnormalities in kids
what is hydronephrosis of urinary tract
dilation of renal pelvis, calyces and ureter due to obstruction
what is hydronephrosis of urinary tract obstruction associated with
atrophy of kidney and blunted papillae
microscopic features that characterize acute urinary tract obstruction-
dilation of tubules & bowman’s space
__________ = formation of stones within urinary tract
urolithiasis
clinical features of urolithiasis depend on
stone size
small stones of urolithiasis would cause
severe pain if enter the ureter, due to obstruction
large stones of urolithiasis would…
stay in renal pelvis & are asymptomatic
types of urolithiasis
calcium
struvite
uric acid
miscellaneous-cystine
which type of urolithiasis forms after infection with urea-splitting bacteria (proteus mainly)?
struvite
which urolithiasis can result in large “staghorn calculi”
struvite (magnesium ammonium phosphate)
which type of urolithiasis is most common?
calcium (oxalate & phosphate)… often associated w increased calcium excretion
benign renal tumors
oncocytoma
angiomyolipoma
papillary adenoma
malignant renal tumors
renal cell carcinoma
wilm’s tumor
urothelial carcinoma
most common cause of renal cell carcinoma?
most are sporadic!
renal cell carcinoma is autosomal __
dominant
clinical features of renal cell carcinoma
hematuria
costovertebral pain
palpable mass
fever, malaise, weakness, weight loss
classification of renal cell carcinoma based on
histology, cytogentics, genetics
clear cell carcinoma most commonly affect
upper pole of kidney
most common type of renal cell carcinoma
clear cell carcinoma
clear cell carcinoma have abundant clear cytoplasm with
accumulation of lipid and glycogen
what is the most common primary renal tumor of children
wilms tumor
wilms tumor has germline mutation in
WT1
clinical features of wilms tumor
large abdominal mass hematuria pain intestinal obstruction HTN
