Intro to Renal Pathology Flashcards
What pathologies tend to affect the glomeruli?
mostly immune mediated
What pathologies tend to affect the tubules?
tend to be from toxic or infectious etiologies such as low BP in exsanguination
What pathologies tend to affect the interstitium?
tend to be from toxic or infectious etiologies as well
Medical kidney (everything excluding tumors) biopsies require a combination of what 3 types of microscopy?
- light microscopy
- immunofluorescence
- electron microscopy
each require a special media to perform and can be used for diagnosis, prognosis, or even guide therapy
What is the composition of the glomerular basement membrane?
The BM is an embryonic fusion of the visceral epithelium and endothelium and is composed primarily of type IV collagen, agrin, and laminin 11
What is the normal density of cells per capillary tuft inside a glomerulus?
1-2 cells per tuft
What are some slit pore diaphragm proteins secreted by podocytes and their function?
nephrin and podocin- play a role in filtration. Mutations result in congenital NEPHROTIC syndromes due to the loss of large amounts of protein in urine
Patients with mutations in nephrin (NPHS1 mutation) or podocin (NPHS2 mutation) present with what disease?
focal segmental glomerulosclerosis (FSGS). This disease is typically primary but can be secondary
What are some primary globular diseases?
- minimal change disease
- FSGS
- membranous nephropathy
- Acute post infectious GN
- Membranoproliferative GN
- IgA nephropathy
What are some secondary globular diseases?
- Lupus nephritis (SLE)
- Diabetic nephropathy
- Amyloidosis
- GN secondary to multiple myeloma
- Goodpasture syndrome
- Micrscopic polyangiitis
- Wegener’s
- Henoch-Schonlein purpura
- Bacterial endocarditis-related GN
- Thrombotic microangiopathy
What are some hereditary globular diseases?
- Alport syndrome
- Fabry disease
- Podocyte/slit-diaphragm protein mutations
How do immune complexes damage the glomeruli?
they get trapped or are formed in-situ and produce injury via activation of complement or the recruitment of leukocytes
T or F. Immune complexes deposited in the endothelium elicit an inflammatory reaction
T. And cause exuberant proliferation of glomerular cells while antibodies directed The sub epithelial region are largely non-inflammatory
Deposition of circulating immune complexes gives what type of immunofluorescence pattern?
granular
Anti-glomerular basement membrane (anti-GBM) antibody glomerulonephritis is characterized by a ____ immunofluorescence pattern.
linear (think Goodpasture’s syndrome)
What causes post-infectious glomerulonephritis (PIGN)?
immune complex disease producing antibodies against streptococcal pyogenic exotoxin B
What do you see on light microscopy for PIGN?
early on glomeruli are globally and diffusely enlarged and hyper cellular due to neutrophils (inflammation).
Returns to normal within months so they don’t typically biopsy.
What do you see on electron microscopy for PIGN? Buzzword
formation of subepithelial ‘hump’s above the BM
What causes Goodpasture’s syndrome?
anti-glomerular basement membrane antibody targeting the alpha-3-chain of type IV collagen (also in the lung)
What are the symptoms of Goodpasture’s?
- SOB
- Coughing up blood
- Fever
- Unplanned weight loss
- Fatigue
T or F. Serologic testing for anti-GBM in patient serum is often positive
T.
Rapidly progressive glomerulonephritis is a common clinical syndrome associated with a number of diseases. What is the the suspected etiology?
immune mediated (about half have immune complex GN with crescents and half have pouch-immune crescentic GN)
How is rapidly progressive glomerulonephritis characterized?
- progressive loss of renal function
- lab findings typical of NEPHRITIC syndrome
- often severe oliguria (why?)
Prognosis of rapidly progressive glomerulonephritis?
often leads to death from renal failure within a period of weeks to months if untreated
What is the characteristic histologic finding associated with RPGN?
presence of crescents (crescentic GN)
remember, this can happen in a variety of diseases and is a syndrome, not a disease
What causes crescent formation?
proliferation of cells around the glomerulus that compresses it and eventually causes it to lose function and become sclerotic
What is Pauci-immune crescentic GN?
defined by the lack of anti-GBM antibodies or of significant immune complex deposition detectable by immunofluorescence and electron microscopy and are typically associated with ANCAs
What do the glomeruli show in PIC GN?
segmental necrosis and GBM breaks with resulting crescent formation
What would immunoflourescence of PIC GN show? EM?
might be slightly green but are negative for immunoglobulin or complement and no deposits are detectable by EM
What is the basis of hemodynamic glomerular injury?
hydrostatic pressure is higher in the glomerular capillaries than others and is also higher than the 18 mm Hg in Bowman’s space, driving filtration.
But, above normal glomerular capillary pressures injure them
What does hemodynamic glomerular injury stimulate?
- GBM thickening
- mesangial cell hypertrophy
- Hyperplasia and mesangial matrix production
these lead to decreases ability to filter
The term for end-stage hypertensive nephropathy is ______.
arterionephosclerosis
What happens in malignant HTN?
injury results in increased permeability of the small vessels to fibrinogen and other plasma proteins, endothelial injury, and platelet deposition leading to fibrinoid necrosis of arterioles leading to necrosis of glomeruli
also see onion-skinning of arterioles cell to proliferation of intimal cells
NON SPECIFIC
Full-blown malignant HTN is characterized by what?
- papilledema
- encephalopathy
- CV abnormalities
- renal failure
What is thrombotic microangiopathy?
widespread thrombosis in the microcirculation characterized by microangiopathic hemolytic anemia and thrombocytopenia
What are some primary diseases that thrombotic microangiopathy is seen in?
- HUS and aHUS
- TTP
What are some secondary diseases that thrombotic microangiopathy is seen in?
- malignant HTN
- Drug-induced (chemo, cocaine)
- pregnancy (HELLP)
- DIC, malignancy, HIV
- SLE, CREST
T or F. You cannot tell histologically what is the cause of end-stage chronic kidney disease
T.
