Renal Pathology II Flashcards
What are the characteristics of rapidly progressive glomerulonephritis (RPGN)?
It is a clinical syndrome characterized by a rapid and progressive loss of renal function, often with severe oliguria, and laboratory findings typical of the nephritic syndrome. Crescents are a classical finding of RPGN.
What are crescents?
Crescents are formed by proliferation of the parietal epithelial cells, shaped into a crescent-like structure, as they fill the Bowman’s space. The proliferation of parietal cells is in response to severe injury of the glomerular basement membrane resulting in necrosis and breaks with leakage of blood and fibrin to the urinary space.
What is the problem with crescent formation?
Crescents obliterate the urinary space and compress the tuft, with shutting-off of blood circulation and filtration; rapid renal failure ensues.
What are the types of RPGN and what are they caused by?
Type I - anti-glomerular basement membrane antibody mediated glomerulonephritis
Type II - severe immune-complex glomerulonephritis
Type III - pauci- immune/ANCA associated glomerular injury
What is the pathogenesis of RPGN Type I?
Anti-glomerular basement membrane antibodies form often from exposure to things like paints, dyes, drugs, smoking, etc.
What is the typical patient of RPGN Type I?
Young men - although the cases are RARE
What are the clinical presentations of RPGN Type I?
- gross hematuria
- drop in urinary output (acute renal failure)
- hemoptysis (lung is affected)
What are the lab findings for RPGN Type I?
- Linear Stain for IgG
- Crescents
- Anti-glomerular basement membrane antibodies in serum
Why is there gross hematuria in RPGN Type I?
The glomerular basement membrane is RAPIDLY destroyed, leading to widespread necrosis - holes - that causes the “sieve” effect
What is Goodpasture Syndrome?
Antibodies in RPGN Type I will have cross reaction with with pulmonary alveolar basement membrane, causing pulmonary hemorrhage associated with renal failure - DEADLY
What is the treatment of RPGN Type I?
Plasmapheresis to remove the Ab
What is the pathogenesis of RPGN Type II?
Severe immune complex formation leads to necrosis and breaks in glomerular basement membrane
What is the typical patient of RPGN Type II?
Children and young adults (10-40 yo)
What are the clinical presentations of RPGN Type II?
- gross hematuria
- drop in urinary output (acute renal failure)
What are the lab findings of RPGN Type II?
- crescents
- immune complexes (IgG+C3; IgA+C3)
- electron dense deposits by electron microscopy
What are the two main etiologies of RPGN Type II?
- IgG-C3 in postinfectious glomerulonephritis and lupus
- IgA-C3 complexes in IgA nephropathy
What is the pathogenesis of RPGN Type III?
Antineutrophil cytoplasmic autoantibodies (ANCA), react with neutrophil cytoplasmic antigen but do NOT form immune complex.
What is the typical patient of RPGN Type III?
Older female
What are the clinical presentations of RPGN Type III?
- drop in urinary output (acute renal failure) gross - hematuria
- other: hemoptysis, shortness of breath
What are the lab findings of RPGN Type III?
- antineutrophil cytoplasmic autoantibodies
- crescents
What will be the immunofluorescence and EM findings in RPGN Type III?
NEGATIVE. They will be normal
What is RPGN Type III AKA?
Pauci-immune RPGN
What are ANCAs?
ANCAs are antibodies against constituents of neutrophiles primary granules. ANCAs are a highly sensitive diagnostic marker of pauci-immune glomerulonephritis/systemic vasculitis. ANCAs play a role as a direct cause of pauci- immune glomerulonephritis/systemic vasculitis by inducing premature degranulation and activation of neutrophiles with release of lytic enzymes
What is a possible complication or co-finding with RPGN Type III?
Systemic vasulitis:
a. microscopic polyangiitis
b. pulmonary angiitis and granulomatosis (aka Wegener granulomatosis)
c. Churg-Strauss syndrome
What is Wegener granulomatosis and what is the main form of ANCA mediating these effects?
cANCA.
Vasculitis with necrosis and granuloma-like pathology that affects: Ear/nose/throat, Lung and Kidney
What is a major clinical presentation of RPGN Type III?
Recurrent sinusitis
What is Churg-Strauss syndrome?
Small vessel vasculitis associated with peripheral eosinophila, asthma and necrotizing granulomas
What is the main ANCA mediating Churg-Strauss syndrome?
pANCA
What are the major features of RPGN?
nephritic syndrome + renal failure
The main characteristic is severe glomerular injury with crescents.
What are the general features of nephrotic syndrome?
- massive proteinuria, with daily protein loss in the urine of 3.5 g or more in adults
- hypoalbuminemia, with plasma albumin levels less than 3g/dL
- generalized edema = most obvious clinical manifestation
- hyperlipidemia and lipiduria
Why does nephrotic syndrome lead to lipiduria?
It is presumed that hypoalbuminemia triggers increased synthesis of lipoproteins in the liver. Lipiduria reflects the increased permeability of the GBM to lipoproteins.
How is albumin filtration prevented?
A combination of small pore size and negatively charged pore-forming molecules prevents albumin filtration
What is the typical presentation of membranous nephropathy?
- edema where loose connective tissue is (eyes)
- thrombosis - loss of anti-thrombin III
- infections
What is the typical patient of membranous nephropathy?
Young/middle age adults between 30 and 60 years of age
What is the pathogenesis of membranous nephropathy?
In-situ subepithelial immune complex formation that causes anautoimmune response against renal antigen
What are some possible causes of membranous nephropathy?
Carcinomas: lung, colon, breast, kidney
Infections: malaria, hepatitis
Drugs: penicillamine, gold
What ethnicity is membranous nephropathy most often found it?
Caucasians
What are the lab findings of membranous nephropathy?
- No inflammation
- No proliferation
- Capillary wall thickening with IgG + Complement granular subepithelial electron dense deposits and loss of foot processes
- Hypoalbuminemia, hyperlipidemia and lipiduria
What happens to the level of complement in membranous nephropathy?
The levels are normal as the deposition is slow
What is the microscopic appearance in membranous nephropathy?
“Spike and dome”
The nephrotic syndrome is characterized by severe proteinuria, decreased serum albumin level, and edema. This result from damage to one or more components of the glomerular capillary wall. In particular, the glomerular basement membrane is essential for maintaining serum oncotic pressure. In nonpathologic states, which of the following properties of the florular basement membrane prevent albumin from being freely filtered into the urine?
- (A) A combination of small pore size and negatively charged pore-forming molecules prevents albumin filtration
- (B) A combination of small pore size and positively charged pore-forming molecules prevents albumin filtration
- (C) Albumin is freely filtered across the basement membrane but is readily reabsorbed along the nephron
- (D) The positive charge of proteoglycans in the basement membrane repels albumin
- (E) The small size of the glomerular basement membrane pores excludes albumin molecules
• (A) A combination of small pore size and negatively charged pore-forming molecules prevents albumin filtration
A 50-year-old man with a history of large bowel obstruction is diagnosed with colon cancer and undergoes resection of his colon. He returns to his physician for his regular checkup and complains that in the past 3 weeks he has not been feeling well and has noticed significant swelling of his legs. On physical examination, the physician notes 2+ pitting edema and a blood pressure of 155/94 mm Hg. Urinalysis shows 4+ protein with no RBCs or casts. The patient has otherwise been healthy. Which of the following would most likely be present on a kidney biopsy from this patient?
- (A) A spike-and-dome pattern of deposition on silver stain
- (B) proliferative glomerulonephritis
- (C) hump-like subepithelial deposits on light microscopy
- (D) Nonlinear mesangial staining with IgA immunofluorescence
- (E) “Splitting” of the lamina densa
• (A) A spike-and-dome pattern of deposition on silver stain
A 68-year-old man complains of nasal obstruction, bloody nose, cough and bloody sputum. A chest x-ray displays caviated lesions and multiple nodules within both lung fields. Urinalysis reveals 3+ hematuria and red blood cells casts. Laboratory studies show anemia and elevated serum levels of C-ANCA (antineutrophil cytoplasmic antibody). Peripheral eosinophils are not increased. A renal biopsy exhibits focal glomerular necrosis with cresents and vasculitis affecting arterioles and venules. What is the appropriate diagnosis?
- (A) Churg-Strauss syndrome
- (B) Goodpasture syndrome
- (C) Hypersensitivity vasculitis
- (D) postinfectious glomerulonephritis
- (E) microscopic angiitis and granulomatosis (Wegner granulomatosis)
• (E) microscopic angiitis and granulomatosis (Wegner granulomatosis)
A 35-year-old man with a history of smoking presents with hematuria and bloody sputum. Over the next 2 days, he develops oliguria and renal failure, after which he is placed on dialysis. A renal biopsy is stained with antihuman IgG, and the results are shown. Which of the following best described the pattern of direct immunofluorescence observed on this photomicrograph?
- (A) Discontinuous and mesangial
- (B) Finely granular along the perimesangial reflections
- (C) Linear along the glomerular basement membrane
- (D) Mesangial
- (E) Peripheral granular humps
• (C) Linear along the glomerular basement membrane
A 44-year-old man complains of swelling of his legs and puffiness around his eyes. His abdomen has become protuberant and he feels shorts of breath. Physical examination reveals generalized edema and ascites. Total serum protein is 5.2 g/dl (reference = 5.5-8.0 g/dl), and albumin is 1.9 g/dl (reference = 3.5-5.5 g/dl). Serum cholesterol is elevated at 530 mg/dL. There are 5 g of protein in a 24-hour urine collection. The urinary sediment contains many hyalin casts but no RBCs or inflammatory cells. A renal biopsy stained by direct immunofluorescence for IgG is shown. Which of the following is the most likely diagnosis?
- (A) anti-glomerular basement membrane glomerulonephritis
- (B) IgA nephropathy
- (C) hereditary nephritis
- (D) Membranous glomerulopathy
- (E) postinfectious glomerulonephritis
• (D) Membranous glomerulopathy
