nephritic syndrome II
Anti-GBM GN - Clinical Features (II)
• Can present as:
– pure glomerulonephritis
– GN with pulmonary hemorrhage (more
often young men)
= Goodpasture syndrome
Anti-GBM GN - Pathogenesis
• Immune-mediated
• Pts make auto-antibodies against alpha 3
chain of collagen IV
• Auto-antibodies bind to glomerular GBM
and incite inflammation
• Pts have anti-GBM auto-antibodies in serum
– inc. anti-GBM antibody titer in serum
Anti-GBM GN - Light Microscopy
• Damage to glomerular capillary walls
– leak of fibrin into Bowman’s space
• Typically crescent formation
– proliferation of Bowman’s capsule epithelial cells
• Red cell casts in interstitial tubules
Anti-GBM GN - IF and EM
• By immunofluorescence
– LINEAR deposits of IgG and C3 along glomerular basement membrane - only GN with linear staining
• By electron microscopy
– wrinkling of glomerular basement membrane
– focal breaks in glomerular basement membrane
– no deposits
Pauci-Immune GN - (=ANCA Disease)
ANCA = Anti-Neutrophil Cytoplasmic Antibodies
Clinical
• Acute renal failure - medical emergency:
– oliguria, hematuria, red cell casts, Inc. creatinine
• More common in adults, also occurs in children
Pauci-immune GN – Pathogenesis I
• Caused by circulating auto-antibodies
• Auto-antibodies are called “Anti-Neutrophil Cytoplasmic Antibodies” (=ANCA)
• ANCAs bind to proteins in cytoplasm of neutrophils
• ANCAs activate neutrophils
• Activated neutrophils incite inflammation in glomeruli
Pauci-immune GN - Pathologic Features
• Light microscopy:
– Crescentic GN
• Immunofluorescence:
– NO GLOMERULAR STAINING (or slight non-specific staining)
– That’s why it’s called PAUCI-immune GN
pau·ci·ty
Noun
| |
Synonyms
Lupus Nephritis - secondary disease to LE - most danderous aspect of LE
Lupus Erythematosus – Definition
• Auto-immune disease
• More common in females than males (10:1)
• Affects multiple organ systems → multi-system disease
• Clinical presentation highly variable
• Glomerulonephritis WHO class I – VI
• Caused by immune deposits:
– IgG, IgA, IgM, C3, C1q all stain = only in Lupus "Full House"
Lupus – Criteria defined by American College of Rheumatology
Criterion Definition - need 3 of the following
1. Malar rash - erythema over malar excrescences
2. Discoid rash - skin rash
3. Photosensitivity - skin rash after UV exposure
4. Oral ulcers - usually painless
5. Arthritis - joint tenderness, swelling, effusion
6. Serositis - pleual effusion, pericardial effusion
7. Renal disorder - Proteinuria or glomerulonephritis
8. Neurologic disorder - Seizures or psychosis
9. Hematologic disorder - anemia, leukopenia, thrombocytopenia
10. Immunologic disorder - anti-ds DNA, anti Sm, antiphospholipid auto-antibodies
11. Antinuclear antibodies - positive ANA auto-antibodies
Alport Syndrome and Thin GBM Disease |
• Hereditary nephritis = group of familial diseases
– Alport sydrome
– Thin basement membrane disease (=benign familial hematuria)
• Thin basement membrane disease:
– asymptomatic hematuria (miscrocopic)
– familial, but fairly common
– diffuse thinning of GBM
– prognosis excellent
• Cause:
– X-linked inheritance most common
– mutation in gene for alpha 5 chain of collagen IV
• Pathogenesis:
– abnormal assembly of collagen IV
– altered structure and functions of GBM and other basement membranes
Clinical features:
– nephritis
– nerve deafness
– eye abnormalities (lens dislocation, corneal dystrophy)
– express full syndrome
– are carriers
• Renal abnormalities:
– hematuria (micro- or macroscopic)
– proteinuria
– renal failure in adult
Tubulo-Interstitial Diseases
more common than glomerular diseases
- Anatomy of normal nephron
- each normal kidney has 800,000 -1,200,000 nephrons
- Acute tubular necrosis
- Definition:
- – damage to tubular epithelial cells and necrosis
- → acute loss of renal function (renal failure)
- – is clinico-pathologic entity
- Causes:
- – ischemia (typically pre-renal) = first affects tubules
- – toxic (intra-renal)
- – acute tubulo-interstitial nephritis (intra-renal)
- – urinary obstruction (post-renal)
- Ischemia:
- sudden drop in blood pressure (pre-renal)
- shock (severe blood loss, burns, sepsis, acute heart failure, dehydration, prolonged diarrhea)
- → decrease in circulating blood volume
- → hypo-perfusion of kidneys
- → renal tubules oxygen-deprived
- → necrosis of tubular epithelial cells
- Vasculitis:
- vascular inflammation → narrowing of renal
- vessels → hypo-perfusion of kidneys → → →
- Ischemia:
- – tubular cell injury
- → detachment
- → tubular obstruction
- → impaired urine flow in tubules
- → increased intra-tubular pressure
- → decreased GFR
- → tubulo-glomerular feedback (renin-angiotensin, dec. NO, dec. prostaglandin I2)
- → constriction of afferent arteriole supplying the nephron
- → acute renal failure
- Toxic:
- drugs (e.g. antibiotics)
- radio-contrast dyes
- poisons (e.g. mercury, organic solvents)
- myoglobin (released from muscles in crush injury)
- hemoglobin (hemolysis e.g. due to transfusion reaction)
- Acute tubulo-interstitial nephritis
- Definition:
- acute inflammation of tubules and interstitium - nl glomerulus
- Two main causes:
- Infection (typically ascending!)
- drugs - esp. antibiotics, diuretics, NSAIDS
- others (see Robbins p. 996, Table 20-9)
- Clinical features:
- begins 15 days after exposure
- fever, blood eosinophilia, rash
- hematuria, mild proteinuria, leukocyturia with eosinophils
- inc. serum creatinine or acute renal failure
- Pathogenesis: abnormal immune reaction
- Typically: acute hypersensitivity immune reaction
- IgE-mediated hypersensitivity (type I hypersensitivity reaction)
- drug binds to proteins in tubular cells and becomes immunogenic (i.e. functions as a hapten)
- idiosyncratic, i.e. NOT dose-related
- When granulomas present (less common):
- – delayed-type hypersensitivity (type IV hypersensitivity reaction)
- Acute pyelonephritis
- Very common:
- – one of the most common kidney diseases !!!
- Cause: bacterial infection
- ascending from urethra and bladder, typically from pt’s own fecal flora
- Gram-negative bacilli:
- E. coli, Proteus, Klebsiella, Streptococcus faecalis
- hematogeneous via bloodstream (less common)
- Factors that promote infection and inflammation:
- obstruction: stones, tumors, enlarged prostate, pregnancy
- bladder dysfunction (e.g. spinal cord injury, diabetes)
- vesico-ureteral reflux - due to incompetent vesicoureteral valve
- Complications:
- papillary necrosis, typically in diabetics
- areas of gray-white necrosis in tips of renal papillae
- pyelonephrosis
- pus fills renal pelvis, calyces, ureter
- peri-nephric abscess
- inflammation spreads into retro-peritoneal soft tissue
- sepsis → septic shock → potentially life-threatening!!!
- Evolution into chronic inflammation with scarring
- Chronic Pyelonephritis
- polar scars with blunted calices
- tubular atrophy, chronic lymphocytic infiltrate, interstitial fibrosis
- Chronic pyelonephritis
- Urinary tract obstruction (hydonephrosis, obstructive uropathy)
- • Urinary tract obstruction:
- caused by stones, tumors, enlarged prostate, others
- → dilatation of ureter, renal pelvis, renal calices
- → atrophy of renal cortex
- → hydronephrosis
- Myeloma cast nephropathy (myeloma kidney)
- Multiple myeloma = malignant proliferation of
- plasma cells in bone marrow
- Typically associated with Bence-Jones proteins in
- urine
- = immunoglobulin light chains produced by malignant plasma cells
- – appear in the urine
- – can combine with Tamm-Horsfall protein
- → form casts that obstruct tubular lumina
- – cast in tubules cause obstruction and inflammation
- → cast nephropathy
- Sir Henry Bence Jones in 1848:
- – observed peculiar thermoreactivity of urine from multiple myeloma patient
- – urine becomes turbid only between 40 C and 60 C
- Bence-Jones proteins are monoclonal immunoglobulin light chains
- monoclonal protein increased in serum (Mprotein, M-component, or myeloma protein)
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