Renal Pathology - Ben-Dor Flashcards
Nephritic vs Nephrotic disease
• NEPHRITIC-HEMATURIA,
AZOTEMIA,OLIGURIA, EDEMA,
HYPERTENSION
filtering mechanism damaged
• NEPHROTIC-PROTEINURIA,
HYPOALBUMINEMIA,HYPERLIPIDEMIA,
LIPIDURIA
leaky filtration on a molecular level
Histologic Alterations seen in kidneys
• HYPERCELLULARITY-
– CONSTITUENT CELLS: MESANGIAL,
ENDOTHELIAL, EPITHELIAL (CRESCENTS)
inside
– INFLAMMATION
• BASEMENT MEMBRANE THICKENING (best seen with PAS/silver stain)
• HYALINIZATION AND SCLEROSIS-
– PLASMA PROTEIN
Antibodies against the glomerulus-linear, or basal surface-granular. In siute or circulating from elsewhere.
Types of acute nephritic syndromes
What is seen in each?
Post Infectious (Post streptococcal)
• Most common in CHILDREN
• DEPOSITION OF IMMUNE-COMPLEXES
FORMED FROM STREPTOCOCAL
ANTIGENS or pneumo/staph, mumps, measles, hepatitis
• LIGHT MICROSCOPE:
– HYPERCELLULARITY:
• ENDOTHELIAL AND MESANGIAL PROLIFERATION
• NEUTROPHILIC INFILTRATES
• IMMUNOFLUORESCENCE:
– GRANULAR PATTERN (IgG AND COMPLEMENT of strep antigen and antistrep Ab)
• ELECTRON MICROSCOPY:
- Subepithelial humps evidence of immune complex deposit
RAPIDLY PROGRESSIVE
GLOMERULONEPHRITIS:
• GROUP OF CONDITIONS ALL
CHARACTERIZED BY:
• RAPID CLINICAL PROGRESSION
• HISTOLOGY: FORMATION OF Epithelial CRESCENTS BY BOWMAN CAPSULE EPITHELIUM with hyperplasia from fibrin leaked from blood
• ULTRASTRUCTURE: TEARS IN BASEMENT
MEMBRANE
• ANTI GLOMERULAR BASEMENT MEMBRANE DISEASE
(LINEAR DEPOSITS ON I.F.)- GOODPASTURE DISEASE (WHEN PULMONARY INVOLVEMENT)
Which diseases present as nephrotic syndrome and what do they look like?
What are the most common nephrotic syndromes in children and adults?
Diffusely affected nephrotic syndrome:
Minimal Change Disease
• AFFECTS CHILDREN
• LIGHT MICROSCOPIC EXAMINATION:
NORMAL
• ELECTRON MICROSCOPE EXAMINATION:
EFFACED FOOT PROCESSES (fused-allow large negative proteins in)
• IF.- NORMAL (NO IMMUNE COMPLEXES)
Membranous Glomerulopathy
• MOST COMMON CAUSE OF NEPHROTIC
SYNDROME IN ADULTS
• DIFFUSE THICKENING OF GLOMERULAR
BASEMENT MEMBRANE WITH DEPOSITS
OF ELECTRON DENSE IMMUNE COMPLEX
DEPOSITS ON SUBEPITHELIAL SIDE without increased cellularity
Fused podocytes
Stage 1: New complexes
Stage 2: Spikes off of BM form between immune complexes–>granular deposits
Stage 3: BM thickens in engulfing immune deposits
Stage 4: immune deposits resorbed
15% ASSOCIATED WITH ETIOLOGICAL
FACTORS OR OTHER CONDITIONS:
• DRUGS- PENICILLAMINE, GOLD, NSAIDs
• MALIGNANT TUMORS
• SYSTEMIC LUPUS
• INFECTIONS- HEPATITIS, SYPHILIS
• AUTOIMMUNE- THYROIDITIS
BUT 85% IDIOPATHIC!
Focal Segmental Glomerulosclerosis:
• DEFINED BY LIGHT MICROSCOPE
FINDINGS: SCLEROSIS OF PORTIONS
(SEGMENTAL) OF SOME (FOCAL) BUT
NOT ALL GLOMERULI
– PRIMARY IDIOPATHIC FORM
– SECONDARY FORM (HIV, DRUG ADDICTION,
SICKLE CELL DISEASE, OBESITY)
– ADAPTATION TO LOSS OF PARENCHYMA IN
OTHER CONDITIONS
Damage to visceral epithelial cell leads to leakage of plasma proteins (including fibrin, collagen, and immune complexes) and lipids into mesangium (not immune complex disease but a byproduct)
Other Glomerular disorders (nephritic/nephrotic)
What is the end stage of all the diseases?
MEMBRANOPROLIFERATIVE
GLOMERULONEPHRITIS:
LIGHT MICROSCOPY: HYPERCELLULAR
“LOBULAR” GLOMERULI:
– PROLIFERATION OF MESANGIAL CELLS,
LEUKOCYTES, ENDOTHELIUM
– DUPLICATION OR SPLITTING OF BASEMENT
MEMBRANE into 2 parallel lines WITH INTERPOSED CELLS (“TRAMTRACK”)
In adults often secondary to SLE, Hepatitis or other malignancies
Type I-Subendothelial and graunular, Type II-Intramembranous and linear
IgA NEPHROPATHY (BERGER
DISEASE)
mostly in children
• MANIFESTED AS HEMATURIA
• CHARACTERIZED BY IgA DEPOSITS IN
MESANGIUM
• LIGHT MICROSCOPY SHOWS MESANGIAL
CHANGES (CELLULARITY, MATRIX)
• POSSIBLY RELATED TO HENOCH-SCHONLEIN
DISEASE (intestinal vasculitis), ASSOCIATED WITH DISTURBANCE IN
IgA SECRETION demonstrated by immunofluorescence
Chronic Glomerulonephritis
CHRONIC GLOMERULONEPHRITIS
• END STAGE OF PREVIOUS (any, previous findings disappear)
• SOME PTS WITH ABOVE HAVE NO PRIOR
HISTORY OF RENAL DISEASE
• GROSS: KIDNEYS CONTRACTED WITH
GRANULAR SURFACES
• HISTOLOGICALLY OBLITERATION OF
GLOMERULI REPLACED BY AMORPHOUS
MATERIAL: COLLAGEN, MATRIX, PLASMA
PROTEINS
Scarring and pockmarks
Diabetic Nephropathy (what kinds? how?)
• PROTEINURIA OR NEPHROTIC
SYNDROME
• SUSCEPTIBILITY TO PYELONEPHRITIS
• CHRONIC RENAL FAILURE (main morbidity)
Morphological changes: Vascular changes: hyaline arteriosclerosis (in the wall) BM thickening (all over body including kidney) Indular glomerulosclerosis (nodules of mesangeal matrix material in glomerular periphery-Kimmelstein-Wilson) Diffuse mesangial sclerosis
Renal Consequences of Systemic Lupus Erythematosus
5 classes
Varied: Hematuria, proteinuria, nephrotic syndrome
• CLASS I- NORMAL
• CLASS II- MESANGIAL EXPANSION ONLY
• CLASS III- FOCAL AND SEGMENTAL CHANGES:
MESANGIAL AND ENDOTHELIAL
PROLIFERATION, FIBRINOID NECROSIS, ACUTE
INFLAMMATION
• CLASS IV- CHANGES AS IN III BUT DIFFUSE,
MORE SEVERE:
– SUBENDOTHELIAL IMMUNE DEPOSITS PRODUCE
CAPILLARY WALL THICKENING: “WIRE LOOP”
Type V: Looks just like membranous glomerulonephritis with inflammation
Amyloidosis
• SYSTEMIC DEPOSITS OF PROTEINS IN
SPECIFIC CONFIGURATION IN KIDNEY CAUSES
NEPHROTIC SYNDROME - congealed into plated sheets
• HISTOLOGICALLY WAXY PINK EOSINOPHILIC
DEPOSITS IN GLOMERULI, BLOOD VESSEL
WALLS
• DIAGNOSIS CONFIRMED BY POSITIVE STAINING
WITH CONGO-RED AND APPLE GREEN
BIREFRINGENCE ON EXAMINATION WITH
POLARIZED LIGHT.
Etiology unknown- could be myeloma
Diseases of Blood Vessels: Benign Nephrosclerosis
• THICKENING OF WALLS OF RENAL
ARTERIOLES AND SMALL ARTERIES
ISCHEMIC PARENCHYMAL
CHANGES IN KIDNEY
• INCIDENCE AND SEVERITY INCREASED
IN HYPERTENSION, DIABETES
Happens on its own or with other diseases
Become shrunken and granular due to fibrotic changes
• THICKENING OF WALLS OF ARTERIOLES BY EOSINOPHILIC (PINK) DEPOSITS OF PLASMA PROTEINS, BASEMENT MEMBRANE MATERIAL.
Smaller arteries: thickened intima with elastic fibers
LARGER ARTERIES:
– FIBROELASTIC HYPERPLASIA: MEDIAL HYPERTROPHY, ELASTIC LAMINA REDUPLICATION, THICKENING OF INTIMA BY YOUNG (MYOFIBROBLASTIC) CONNECTIVE TISSUE
• PATCHY ISCHEMIC ATROPHY OR
SCARRING:
– TUBULAR ATROPHY AND INTERSTITIAL
FIBROSIS
– GLOMERULAR COLLAPSE, FIBROSIS and inflammation.
“Thyroidization” of tubules becoming follicular.
CLINICAL REPRECUSSIONS OF
NEPHROSCLEROSIS:
• IN OF ITSELF: LITTLE OR NONE
• HOWEVER RISK OF RENAL FAILURE
INCREASED IN PTS WITH MORE SEVERE
HYPERTENSION, BLACKS, AND DIABETICS
Basis for renal dysfunction
Blood vessel diseases: Malignant, accelerated hypertension and nephrosclerosis
Sudden
• MAY APPEAR DE NOVO, BUT OFTEN IN PATIENTS WITH:
– PRE-EXISTING HYPERTENSION EITHER IDIOPATHIC
OR SECONDARY,
– OTHER RENAL DISEASES (G-N., REFLUX)
– SCLERODERMA
• CLINICALLY: HIGH DIASTOLIC PRESSURES, ELEVATED INTRACRANIAL PRESSURE, EVENTUAL RENAL FAILURE
Fibrinoid necrosis in arterioles.
CHANGES IN LARGER ARTERIOLES AND SMALL ARTERIES:
• “ONION SKINNING”- INTIMAL THICKENING CAUSED BY CONCENTRIC LAYERING OF SMOOTH MUSCLE CELLS, COLLAGEN, AND GROUND SUBSTANCE AROUND LUMEN.
Systemic Hypertension Secondary to Renal Pathology
• ACUTE GLOMERULONEPHRITIS (mainly nephritic)
• CHRONIC RENAL DISEASES (relenting post infectious)
• RENAL ARTERY STENOSIS SECONDARY TO:
– ATHEROMATOUS PLAQUE (ischemic kidney causes angiotensin to be release)
– FIBROMUSCULAR DYSPLASIA: FIBROMUSCULAR
THICKENING OF INTIMA, MEDIA, OR ADVENTITIA
• RENAL ARTERY PATHOLOGY RELATIVELY RARE
BUT SURGICALLY CORRECTABLE
Renal Infarction
• CHARACTERISTICALLY ISCHEMIC TYPE
• MOST OFTEN EMBOLIC FROM HEART:
• USUALLY FROM MURAL THROMBI
SECONDARY TO MYOCARDIAL INFARCTION
• ALSO FROM VEGETATIONS, THROMBUS IN
ANEURYSM. Clumps of fibrin in valve.
Blood clots from injured tissue dislodges and sticks in kidney vessel
In autopsy: can see grossly wedge shape and sharp adges. Apex points to obstructed vessel. Part fed by particular vessel well delineated.
Histology: hyaline infarct (waxy, not much structure), amorphous cells with no nuclei
Tubulo-Interstitial Disease: Acute Tubular Necrosis
• INJURY TO AND DESTRUCTION OF
TUBULE EPITHELIAL CELLS from substances normally found in the blood
• ACUTE DIMINUTION OR LOSS OF
RENAL FUNCTION–>RENAL FAILURE
Causes:
• ACUTE ISCHEMIC PATTERN:
– HYPOTENSION AND SHOCK (TRAUMA, ACUTE
PANCREATITIS).
– HEMOGLOBINURIA (MISMATCHED TRANSFUSIONS–>hemolysis)
AND MYOGLOBINURIA (SKELETAL MUSCLE INJURIES–>crush injury)
• NEPHROTOXIC:
– DRUGS (GENTAMICIN)
– HEAVY METALS (MERCURY)
– RADIOGRAPHIC CONTRAST MATERIAL
• ISCHEMIC TYPE-
– MULTIPLE FOCI OF EPITHELIAL DAMAGE AND
NECROSIS IN VARIOUS PORTIONS OF TUBULE
– RUPTURE OF BASEMENT MEMBRANE
– INTRATUBULAR CASTS (EOSINOPHILIC HYALINE AND PIGMENTED) COMPOSED OF PROTEINS SECRETED BY injuring substance in TUBULE CELLS, HEMOGLOBIN, MYOGLOBIN
– CAN REGENERATE AND RETURN TO NORMAL
NephroTOXIC TYPE:
• DAMAGE MOSTLY IN PROXIMAL TUBULE
• DIFFERENT AGENTS MAY CAUSE (depending on agent)
CHARACTERISTIC PATTERNS OF INJURYINCLUSIONS, FATTY CHANGE,
BALLOONING, no pigmented cast
HISTOLOGY OF A.T.N.: CELL DAMAGE, SLOUGHING
INTO LUMEN, DENUDATION, DILATATION OF TUBULES WITH CELL FLATTENING,CAST FORMATION
INITIAL PHASE OF A.T.N. SHOWS BLEBBING OF
APICAL SURFACES OF CELLS WHICH
DESQUAMATE INTO LUMEN. Swelling on apical side from discharge.
FLATTENING OF TUBULAR EPITHELIAL
CELL, desquamate into lumen. Tubular lumens filled with necrotic cell debris from damage.
Dialysis leads to regeneration
Acute Pyeolonephritis
• INFECTION OF THE KIDNEY-
– ASCENDING FROM THE LOWER URINARY
TRACT (colon-like bacteria)
• INSTRUMENTATION
• VESICOURETERAL REFLUX
– HEMATOGENOUS
• SEPSIS (seeding, often staph)
• IMMUNOCOMPROMISED PATIENT
• DISTANT FOCUS: ENDOCARDITIS (cortical abscesses-collections of neutrophils)
Tubules filled with PMNs, pus filled.
Healing:
• SCARRING OF CORTEX ASSOCIATED
WITH DEFORMATION OF UNDERLYING
CALYX AND PELVIS. Fiibrotic scar forms where abscess was.
• CHRONIC INFLAMMATION
In diabetes: Acute Renal Papillary Necrosis
Chronic Pyelonephritis
- REFLUX ASSOCIATED
- OBSTRUCTION ASSOCIATED
Most common: enlarged prostate in elderly men
Problems evacuating urine because of a problematic valve at the end of the ureter. Chronic regurgitating ureter –> chronic infection
Scarring is wide, irregular and asymmetric with lots of interstitial inflammation (smoldering infection-lymphocytes and plasma cells), enlarged deformed calyces, thyroidization of dilated tubules.
