Pathology Flashcards
4 basic morphologic components of Renal Disease
- glomeruli
- tubules
- interstitium
- blood vessels
Azotemia
elevation of BUN and creatinine level seen in both acute and chronic kidney injury
Prerenal azotemia
hypoperfusion of the kidneys
hemorrhage, shock, volume depletion and CHF that impairs renal function in the absence of parenchymal damage
postrenal azotemia
urine flow is obstructed beyond the level of the kidney
uremia
azotemia associated with a constellation of clinical signs, symptoms, and biochem abnormalities
failure of renal excretory function
metabolic and endocrine abnormalities secondary to renal damage
4 Stages of Renal Failure
- Diminished renal reserve
- renal insufficiency
- chronic renal failure
- end-stage renal disease
Explain what diminished renal reserve is
GFR is ~50% of normal
serum BUN and creatinine values are normal
patients are asymptomatic
This is stage 1 of renal failure
Explain what renal insufficiency is
This is stage 2 of renal failure
GFR is 20-50% of normal
Azotemia appears associated with anemia and HTN
polyuria and nocturia secondary to decreased concentrating ability
Explain what chronic renal failure is
This is stage 3 of renal failure
GFR is t regulate volume and solute composition causing edema, metabolic acidosis and hyperkalemia
Explain what end-stage renal disease is
This is stage 4 of renal failure
GFR <5% of normal
terminal stage of uremia
Nephritic
hematuria (RBC casts) HTN Azotemia Oliguria Proteinuria (<3.5g/day)
Nephrotic
severe proteinuria (>3.5g/day)
hypoalbuminemia (<3g.dL)
generalized edema, hyperlipidemia, lipiduria
Hypercellularity
inflammatory diseases
cellular proliferation - mesangial or endothelial cells
leukocytic infiltration
formation of crescents -accum of cells of proliferating parietal epithelial cells and infiltrating leukocytes
What does Basement membrane thickening look like?
thickening of capillary arteries
on EM - deposition of amorphous electron-dense material like immune complexes
- on endothelial or epithelial side on BM
thickening from increased synthesis of protein components (glomerulosclerosis)
Hyalinosis
accumulation of homogenous eosinophilic material
composed of plasma proteins insudated from circulation into glomerular structures
can obliterate capillary lumens of glomerular tuft
commonly in segmental glomerulosclerosis
sclerosis in kidneys
accumulations of extracellular collagenous matrix
- confined to masangium or capillary loops or both
form fibrous adhesions
Acute Proliferative (Poststreptococcal, Postinfectious) Glomerulonephritis Cause and Age group
Diffuse proliferation of glomerular cells, influx of leukocytes
caused by immune complexes
1-4 weeks after strep
children 6-10 (rarely adults)
Acute Proliferative (Poststreptococcal, Postinfectious) Glomerulonephritis on light microscopy
Enlarged, hypercellular glomeruli Infiltration by leukocytes Proliferation of endothelial and mesangial cells Crescent formation—severe Interstitial edema and inflammation Tubules often contain red cell casts
Acute Proliferative (poststreptococcal postinfectious) glomerulonephritis Granular deposits
depositis IgG, IgM, and C3 in the mesangium and along the GBM
on EM will be on epithelial side of membrane looks like “humps”
Acute Proliferative (poststreptococcal postinfectious) glomerulonephritis Clinical Course
young child
abrupt malaise, fever, nausea, oliguria and hematuria
usually 1-2weeks after sore throat
Red cell casts in the urine
Mild proteinuria (usually less than 1 gm/day)
Periorbital edema
Mild to moderate hypertension
Acute Proliferative (poststreptococcal postinfectious) glomerulonephritis Lab Findings
elevations of antistreptococcal Ab titers
decline in serum concentration of C3
Rapidly Progressive Glomerulonephritis
AKA crescentic glomerulonephritis
Rapid and progressive loss of renal function
Severe oliguria and signs of nephritic syndrome
Crescents - Proliferation of parietal epithelial cells lining Bowman capsule
Infiltration of monocytes and macrophages
can have fibrin strands between cellular layers of the crescents
3 Groups of Rapidly Progressive Glomerulonephritis
- Anti-GBM Ab-induced disease (Goodpasture)
- Immune complex deposition
- Pauci-immune type
Goodpasture Syndrome
Anti-GBM Ab-induced dx
Linear deposits of IgG and C3 (most cases) in the GBM
Plasmapheresis
Serum has anti-GBM antibodies
Immune Complex Deposition of rapidly progressive glomerulonephritis
Post-infectious, LN, IgA nephropathy, HSP
Granular pattern of staining
Treat underlying disease
Granular immune deposits
Pauci-immune type
Lack of anti-GBM antibodies or immune complexes by IF and EM
Circulating antineutrophil cytoplasmic antibodies (ANCAs)
Little or no deposition of immune reactants
Gross exam of rapidly progressive glomerulonephritis
kidneys are enlarged and pale
petechial hemorrhages on cortical surfaces
rapidly progressive glomerulonephritis on EM
Deposits (immune complex cases)
Distinct ruptures in the GBM
Rapidly Progressive Glomerulonephritis
Clinical Course
Hematuria with red blood cell casts in the urine
Moderate proteinuria–can reach nephrotic range
Variable hypertension and edema
as it progresses - severe oliguria
Rapidly Progressive Glomerulonephritis
Serum Analysis
Anti-GBM antibodies
Antinuclear antibodies
Antineutrophil cytoplasmic antibodies
Membranous Nephropathy
Common cause of the nephrotic syndrome in adults
Diffuse thickening of the glomerular capillary wall
Accumulation of electron-dense, Ig-containing deposits along the subepithelial side of the basement membrane
Must have either - underlying malignant tumor, SLE, infection like hepB or C, syphilis, schistosomiasis, malaria, or other autoimmune disorders like thyroiditis
Membranous Glomerulopathy on light microscopy
Glomeruli
Normal in the early stages of the disease
Exhibit uniform, diffuse thickening of the glomerular capillary wall
Membranous Glomerulopathy on EM and immunofluorescence
EM - Irregular dense deposits of immune complexes
Between the basement membrane and the overlying epithelial cells
IF - granular deposits of both Ig and complement
Membranous Glomerulopathy Clinical
slow onset of nephrotic syndrome, hematuria, mild HTN in 15-35%
poor prognosis is concurrent sclerosis of glomeruli
spontaneous remission more in women
most common cause of nephrotic syndrome in children
minimal change disease
Minimal Change Disease peak incidence and tx
Peak 2-6years
follos respiratory tract infections of after immunization
Responds to corticosteroids
Minimal Change disease on light microscopy and EM
LM - normal glomeruli
EM - diffuse effacement of foot processes of visceral epithelial cells in glomeruli
In adults, what is associated with minimal change disease?
hodgkin lymphoma
Clinical Feature of Minimal Change Disease
massive proteinuria, good renal function, no HTN or hematuria
Focal Segmental Glomerulosclerosis
sclerosis in some of glomeruli showing capillary tufts
nephrotic syndrome or heavy preoteinuria
has different types
primary disease is idiopathic
possible diseases associated with focal segmental glomerulosclerosis
HIV, heroin addicition, sickle cell disease and massive obesity
secondary event of Focal Segmental Glomerulosclerosis
IgA nephropathy
Adaptive response of Focal Segmental Glomerulosclerosis
reflux nephropathy, hypertensive nephropathy, unilateral renal agenesis
Focal Segmental Glomerulosclerosis - light microscopy
focal, segmental lesions in some glomeruli
lipid droplets, foam cells
hyalinosis and thickened afferent arterioles
Vairant is collapsing glomerulopathy - retraction or collapse of glomerular tuft (characteristic of HIV assoc nephropathy)
immunofluorescence microscopy - what deposits and where
IgM and C3
sclerotic areas and.or mesangium
Membranoproliferative Glomerulonephritis (MPGN)
2 types
alters glomerular BM, proliferation of glomerular cells, leukocyte infiltration
combo of nephrotic and nephritic
Primary MPGN
idiopathic
type I and type II
Type II is dense depositi disease
Secondary MPGN
systemic disorders/known etiologic agents
Key words Membranoproliferative Glomerulonephritis
proliferative cells in mesangium
endocapillary proliferation involving capillary endothelium and infiltrating leukocytes
crescents
“lobular appearance:
“double-contour” or “tram-track” appearance
Type I MPGN
majority of cases
discrete subendothelial electron-dense deposits
mesangial and subepithelial deposits
C3, IgG, C1q and C4 in granular pattern
Type II MPGN
dense deposit disease
lamina densa of GBM is ribbon-like, extremely electron dense
C3 in mesangium in circles
C3 irreg or linear foci in BM on either side
mesangial rings
Type II Membranoproliferative Glomerulonephritis
Berger Disease
IgA Nephropathy
IgA in mesangial regions
frequent hematuria
most common glomerulonephritis worldwide
Berger Disease - Glomeruli Appearance
May be normal or show mesangial widening and endocapillary proliferation
- leukocyte in glomerular capillaries
depositis in mesangium (IgA)
also seen: C3, properdin IgG or IgM
Henoch-Schönlein Purpura
Clinical
purpuric lesions on extensor surfaces of arms, legs and booty
pain, vomit, intestinal bleeding
hematuria, nephrotic and nephritic syndrome
3-8years (sometimes adults)
follows URT infection
Henoch-Schönlein Purpura
Morphology
focal mesangial proliferation diffuse mesangial proliferation crescentic glomerulonephritis IgA deposition (sometimes IgG, C3) Subepidermal hemorrhages necrotizing vasculitis of small vessels in dermis
Alport Syndrome
heterohenous familial renal disease glomerular injury hematuria => chronic renal failure red cell casts nerve deafness eye disorders X-linked and autosomal recessive/dominant
Renal disease associated with various eye disorders
Alport Syndrome
lens dislocation, posterior cataracts, and corneal dystrophy
X-linked Alport’s
85% of cases
males express full syndrome
females are carriers and present with hematuria
Autosomal recessive/dominant Alport Syndrome
males and females are equally susceptible to full syndrome
Disease where glomeruli BM have alternative thickening and thinning
Alport Syndrome
Disease with interstitial foam cells filled with neutral fats and mucopolysaccharides
Alport Syndrome
Disease Progression of Alport
focal segmental and global glomerulosclerosis
Disease with pronouced splitting and laminatino of lamina densa *basket-weave”
Alport Syndrome
Ages associated with Alport
symptoms 5-20years
onset of overt renal failure: 20-50years
Diseases associated with Chronic Glomerulonephritis
End-stage glomerular disease
Poststreptococcal glomerulonephritis (adults)
Crescentic glomerulonephritis
Membranous nephropathy, MPGN, IgA nephropathy, and FSGS
Chronic Glomerulonephritis
morphology
symmetrical contraction of kidneys with diffusely granular cortical surfaces
cortex thinned with increase peripelvic fat
obliterated glomeruli due to acellular eosinophilic masses
arterial and arteriolar sclerosis
atrophy
irregular interstitial fibrosis
mononuclear leukocytic infiltration of interstitium
Causes of acute tubular necrosis or acute kidney injury (AKI)
ischemia, direct toxic injury to tubules - drugs, radiocontrast, myoglobin, Hb, radiation
acute tubulointerstitial nephritis (HS rxn to drugs)
urinary obstruction
Acute Kidney Injury Morphology
focal tubular necrosis tubulorrhexis eosinophilic hyaline casts Tamm-Horsfall protein accum leukocytes in vasa recta
Toxins associated with Toxic AKI
primarily affect proximal convoluted tubule
Mercuric chloride - acidophilic
carbon tetrachloride - neutral lipids
ethylene glycol - marked ballooning and hydropic or vacuolar degeneration of prox tubule and calcium oxalate crystals
Acute Tubulointerstitial Nephritis
rapid onset, leukocytes, interstitial edema, focal tubular necrosis
Chronic Tubulointerstitial Nephritis
mononuclear leukocytes, interstitial fibrosis, tubular atrophy
Acute Pyelonephritis
suppurative inflammation of kidney
bacterial and viral (polymavirus)
Hallmarks of Acute Pyelonephritis
Patchy interstitial suppurative inflammation
Intratubular aggregates of neutrophils
Tubular necrosis
3 Complications of Acute Pyelonephritis
papillary necrosis
Pyonephrosis
perinephric abscess
Causes of papillary necrosis
SODA sickle cell obstructive pyelonephritis diabetes analgesics
Pyonephrosis
suppurative destruction of renal parenchyma or loss of kidney function
fever, chills, flank pain
assoc with acute pyelonephritis
perinephric abscess
collection of suppurative material in perinephric space
assoc with acute pyelonephritis
Pyelonephritic scar
inflammation, fibrosis, deformation, of underlying calyx and pelvis
assoc with acute pyelonephritis
Chronic Pyelonephritis
Chronic tubulointerstitial inflammation and renal scarring
involves calyces and pelvis
important cause of kidney destructino in children with severe urinary tract abnormalities
- chronic reflux
- chronic obstructive
Hallmarks of Chronic Pyelonephritis
kidneys irregulrly scarred
coarse, discrete, corticomedullar scars overlying dilated, blunted, or deformed calyces, flattening papillae
thyroidization - Dilated tubules with flattened epithelium filled with colloid casts
periglomerular fibrosis
Analgesic Nephropathy
type of chronic renal disease
cause: excessive analgesics
Chronic tubulointerstitial nephritis and renal papillary necrosis
Morphology of Analgesic Nephropathy
normal or smaller kidney cortical atrophy over necrotic papillar cortical loss, atrophy of tubules papillar with necrosis, calcification, fragmentation and sloughing interstitial fibrosis and inflammation
Clinical Analgesic Nephropathy
women > men
recurrent headaches and muscle pain, GI upset, HTN
psychoneurotic, factory workerstips of necrotis papillar are excreted causing hematuria or renal colic
withdrawal of drug = renal fx stabilizes or improves
Acute Uric Acid Nephropathy
precip of urate crystals in tubules (collcting ducts)
obstructs nephrons
leukemias and lymphomas undergoing chemo
Chronic Urate Nephropathy (gouty nephropathy)
Deposition of monosodium urate crystals in distal tubules, collecting ducts, interstitium
birefringent needle-like crystals in the tubular lumens or interstitium
Tophus
tophus
foreign-body giant cells, other mononuclear cells and a fibrotic reaction
nephrolithiasis
uric acid stone in 22% with gout
42% with secondary hyperuricemia
Urolithiasis (Gender and Age)
Men > women
20-30y/o
herediatry predisposition
types of caliculi
Calcium Stone (70%)
Triple Stone of Strucite Stones (15%)
Uric Acid Stones (5-10%)
Cystine (1-2%)
calcium stone
Calcium oxalate or calcium oxalate mixed with calcium phosphate
triple stones or struvite stones
Magnesium ammonium phosphate
Largest stones; staghorn calculi
Infections by bacteria (Proteus and some staphylococci)
uric acid stone
Hyperuricemia (gout)
Radiolucent
Sporadic
abnormal metanephric differentiation
Persistence in the kidney of abnormal structures -
Cartilage, undifferentiated mesenchyme, and immature collecting ductules
Multicystic Renal Dysplasia
Multicystic Renal Dysplasia Morphology
enlarged, multicystic kidney
lined by flattened epithelium
islands of undifferentiated mesenchyme with cartilage and immature collecting ducts
Autosomal-Dominant Polycystic Kidney Disease
Multiple expanding cysts of both kidneys (4kg/kidney)
Destroy the renal parenchyma and cause renal failure
high penetrance
cysts are 3-4cm filled with clear, serous fluid or turbid red/brown fluid that come from tubules
ADULT
Autosomal-Recessive Polycystic Kidney Disease
who it affects, what gene?
CHILD
Perinatal, neonatal, infantile, and juvenile subcategories
Time of presentation and presence of associated hepatic lesions
Mutations of the PKHD1 gene
Autosomal-Recessive Polycystic Kidney Disease
Morphology
enlarged kidneys with smooth external appearance Numerous small cysts in the cortex and medulla Spongelike appearance Cysts Uniform lining of cuboidal cells Origin from the collecting ducts Liver has cysts Associated portal fibrosis Proliferation of portal bile ducts
Medullary Sponge Kidney
sporadic
BL cystic dilations of medullary collecting ducts
Normal cortex
presents in adulthood
asymptomatic with normal renal fx
Dx with IV pyelography
Normal sized kidneys, mult small cysts in medullary pyramids and papillae
Diseases associated with Medullary Sponge Kidney
Marfan’s
Caroli’s
Ehlers-Danlos
Medullary Sponge Kidney - Microscopic findings
Medullary cysts lined by cuboidal epithelium or urothelium
Severe inflammation and scarring in interstitium
Tubular atrophy near papillary tips
Renal Papillary Adenoma
Benign Tumor small, discrete from renal tubular epithelium complex, branching, papillomatous structures size of tumor of 3cm will metastasize
Angiomyolipoma
Benign Tumor
vessels, smooth muscle and fat
25-50% patients with tuberous sclerosis
susceptible to spontaneous hemorrhage
Oncocytoma
Benign Tumor composed of large eosinophilic cells small, round nuclei with large nucleoli from intercalated calls of collecting ducts Tan/ Mahongany Brown and encapsulated NUMBEROUS MITOCHONDRIA
Renal Cell Carcinoma
6th-7th decade 2:1 male risk factor: tobacco from tubular epithelium yellow in color Includes: Collecting duct (Bellini duct) carcinoma, chromophobe, papillary and clear cell carcinoma
Clear Cell Carcinoma
70-80% renal cancers
derive - prox tubule
orange/yellow (lipid), upper pole, hemorrhage, necrosis and calcification
freq involve renal vein and renal sinus
bilateral clear cell carcinoma
in 1%
von Hippel Lindau
tuberous sclerosis
Clear cell carcinoma - microscopic
Compact, tubulocystic, alveolar patterns
Clear/granular cytoplasm (glycogen/lipid)
Cell size is 2x normal epithelial tubule cell
Clear Cell Carcinoma Genetics
deletion of short arm chromosome 3 (-3p)
Papillary Carcinoma
%, origin, size
10-15% renal cancers
AKA chromophil renal carcinoma
origin: prox or distal convoluted tubules
size >5mm
Papillary Carcinoma - Microscopic
Well-circumscribed, often with distinct fibrous capsule
Papillary growth pattern
Foamy macrophages and intracellular hemosiderin
Forms of Papillary Carcinoma
Sporadic: Trisomies 7, 16, 17 and loss of Y in men
Familial: trisomy 7
Chromophobe Renal Carcinoma
%, origin, gross
5% renal cancers
origin: intercalated cells of collecting ducts
well-circumscribed, tan brown, geographic necrosis
~8cm
Excellent prognosis
Chromophobe Renal Carcinoma - Microscopic
nests or broad alveoli/trabeculae
Prominent cell membranes and pale eosinophilic cytoplasm
Halo around the nucleus
Positive for Hale’s colloidal iron stain
Chromophobe Renal Carcinoma - genetics
multiple chromosome losses and extreme hypodiploidy
Collecting Duct (Bellini Duct) Carcinoma - %, Origin, Gross Prognosis
<1% renal carcinomas
origin: collecting duct cells in medulla
Gross: infiltrative, firm, gray-white, ~5cm, may have intrarenal metastases
Death in weeks-months
Collecting Duct (Bellini Duct) Carcinoma - microscopic
Poorly circumscribed tubulopapillary tumor, infiltrative borders
Nests of malignant cells in fibrotic stroma
Medullary location
Irregular channels lined by high grade hobnail cells
Marked desmoplastic response
Brisk neutrophilic infiltrate
Mucin production
Hyperacute Renal Rejection
within minutes to hours after transplantation
result from: pre-sensitization, imcompatible blood/HLA groups, complement activation
vasc thrombosis and ischemic necrosis
Acute Renal Rejection
first 5-7days post-transplant
CMI injury
delayed HS and cytotoxicity mechanisms
immune injury against HLA expressed by tubular epithelium and vascular endothelium
Banff Schema
acute renal rejection with tubulitis and intimal arteritis
intimal arteritis - infiltration of arterial intima
