Topic 68-73: Renal failure, nephritic, nephrotic Flashcards
what is the difference between end stage kidney and renal failure?
renal failure can lead to end stage kidney.
end stage kidney is the near or total failure of the kidney to function while kidney failure is the process where the kidney doesn’t function properly
What qualifies end stage kidney?
kidney function is below 20%
GFR is below 15 ml/min
kidney doesn’t concentrate urine, removes waste product or regulates endocrine function
what is the first thing to go in kidney dysfunction?
the ability to concentrate urine
so take a specific gravity!
what are the two central symptoms of kidney failure?
azotemia
uremia
what is the difference between uremia and azotemia?
- azotemia is an elevation in BUN and serum creatinine
- uremia is when azotemia progresses to have clinical manifestations and systemic changes
What are the 3 types of azotemia and what do they signify?
- prerenal - any disease that decreases gfr without direct damage to the kidney tissue. shock, hemorrhage
- renal - renal parenchymal damage such as tubular or glomeruli damage
- post-renal - when urine flow is obstructed under the kidney. kidney stone for example
what is the SI BUN:creatine ratio for azotemia?
BUN:C
when creatine is changed to mmol/l (divide by 1000)!
40-100:1 = normal >100:1 = pre-renal <40:1 = renal
uremia is associated with which symptoms?
- confusion, lethargy, edema, weakness - buildup of waste
- Electrolyte imbalance (hyperkalemia, hyperphosphatemia and hypocalcemia)
- cardiopulmonary
- anemia due to low EPO
- neural
- retinal
- dermal
- respiratory - kussmaul breathing, bad breath
- GI
- metabolic acidosis
uremia leads to encephalopathy, pericarditis, or hypocalemia
acute renal failure is what? what are the three types?
sudden reduction in renal function with oliguria/anuria
-prerenal - shock, hemorrhage, salt depletion, dehydration
- renal - acute nephropathy
- post-renal - urine flow obstruction
chronic renal failure is due to what?
basically all the chronic nephropathies
- primary glomerular disease
- prim. tubular disease
- vascular disease
- infections
- obstruction
- collagen
- metabolic renal
- congenital anomalies
-ischemia
what are the renal developmental abnormalities?
- complete or bilateral agenesis
- unilateral agenesis
- renal ectopia
- horseshoe kidney (normally lower pole fusion)
- duplicated ureter
- Polycystic kidney disease
What are the cystic diseases of the kidney?
- simple
- dialysis acquired cyst
- dominant and recessive polycystic kidney disease
- medullary cystic kidney disease
which type of Polycystic kidney disease is more common? which is more severe?
dominant type PKD is more common
recessive type is more severe and incompatible with life
what is the mutation associated with the autosomal PKD?
in 90% - deletion of PKD1- gene on chrom 16 - encodes polycystin that helps develop tubular epithelium and without it there is a dysfunctional tubule formation
in a few cases PKD2-gene is mutated and this has a better prognosis
what is the mutation associated with the recessive PKD?
PKHD1 gene on chrom 6 - encodes fibrocystin
leads to dysgenesis of the collecting tubules thus early onset RF
morphologically how do the two diseases differ?
autosomal type : large cysts, very large kidney
recessive type: small cysts, sponge kidney
When it comes to glomerular disease, the categorization stems from clinical, pathologist and immunologist terminology. what are the 5 types of glomerular clinical categorizations?
based on symptoms
- acute nephritic
- chronic glomerulonephritis
- rapidly progressing glomerulonephritis
- nephrotic syndrome
- asymptomatic hematuria
what are the pathologist categorizations?
anatomical
- glomerular hypercellularity
- BM thickening
- sclerosis and hyalinization
immunologist categorization of Glomerular disease?
based on antibody injury
- single antibodies
- immune complexes
What are the three causes of glomerulonephritis?
- primary - IgA nephritis
- postinfectious - post-strep and bacterial endocarditis associated
- secondary to systemic disease - SLE, wegener’s granulomatosis, goodpasture
what is IgA glomerulonephritis? where might the IgA problem stem from? what causes the kidney damage?
- IgA antibodies are attached to the mesangium (Immune complex mediated)
- overproduction, abnormal production and clearance or IgA glycosylation can cause this– lack of glycosylation will cause the fomation of nefritic factor (IgG) that binds the IgA and creates an immune complex
- this will trigger the alt complement pathway thus neutrophils will cause the kidney damage
what is post-strep glomerulonephritis? what is the exact location of the problem? what causes the damage?
- immune complexes of bacterial antigens and antibodies attach to the subendothelial layer
- the mesangium proliferates to remove the ICs –> inflam with complement activation
what kind of G-nephritis does SLE cause?
immune complex mediated
what are the three types of RPGN?
what is a common feature?
- they are all cresent forming due to the proliferation of the bowman’s capsule
- anti-glomerular BM nephritis
- immune complex mediated crescentic GN
- pauci-immune type III gn - necrosis of segments, fragmented BM and cell damage is due to ANCA
what kind of G-nephritis does wegener’s granulomatosis cause?
RPGN - pauci-immune type III gn - necrosis of segments, fragmented BM and cell damage is due to c-ANCA
what kind of G-nephritis does goodpasture cause?
antibody mediated against the alpha 3 chain of type 4 collagen (anti-BM)
nephrotic syndrome is caused by what in children and what in adults?
children - lesion primary to kidney
- focal and segmental glomerulosclerosis
- minimal change disease
- membranoproliferative GN
- membranous nephropathy
adults - renal manifestations of systemic diseases
-diabetes, sle, amyloidosis
what is minimal change disease? what kind of protein is lost? what is treatment?
-MCD is when there glomeruli look normal but in electron microscopy there is a thinning of podocyte foot processes, losing their anion charges
- the proteinuria is mainly small proteins like albumin
- corticosterone therapy
- occurs from cytokine overproduction after infection, possibly in Hodgkin lymphoma
what is focal segmental glom-sclerosis? what does it occur with frequently?
how is it different from MCD?
FSGS is when there is a large deposit of hyaline and lipid droplets that increase mesangial mass, obliterate capillaries and cause sclerosis in the glomeruli.
- Focal because only some of the glomeruli
- segmental only segments of that glomeruli is sclerotic
30% it is primary, the other times they are secondary to other nephropathies (IgA), bad adaptations to kidney removal, hereditary etc (Matolcsy says the same cytokine cause as MCD, basically a more severe MCD)
- MCD is different because FSGS has
- -nonselective hematuria
- -poor corticosteroid therapy response
- -high incidence of hematuria and hypertension
membranous GN is what? most of the time it occurs due to what? what is the morphology?
Membranous GN is an idiopathic (85% of the time) Basement membrane thickening due to: Subepithelial IC deposit on BM and the mesangial cells attempt to remove the IC by invading the BM causing a thickened BM with holes from the removed IC. “spike and dome” appearance
- non-selective proteinuria
- Heterogenous causes, including SLE, drug exposure, some infections (HBV, HCV, syphilis), or some cancers (lung, colon, melanoma)
what is membranoproliferative GN? what are the two main changes? what is the morphology? how many types are there?
membranoproliferative GN is an autoimmune response to an antigen.
it is associated with BM thickening due to proliferation of the mesangial cells and endothelium. “tram track” appearance (Matolcsy: “wire loop” from doubling of basement membrane)
- the glomeruli are large with big lobar appearance
- the bm is thick
MPGN type I and II
What is the general definition of MPGN I and II? what immunohistochem would you see with both?
type I - (80%) has subendothelial immune complex deposits. unknown antigen, associated with HBV and HCV. complement activation. Has more “tram track” appearance: mesangial cells proliferate to try to separate dual basement membrane layers.
type II - (20%) intramembranous IC deposits. has an excessive complement activation that causes the mesangial proliferation and BM thickening. Associated with C3 nephritic factor: autoantibody that attaches to and stabilizes C3 convertase -> overactivation of complement -> inflammation
what are 5 systemic diseases that have a serious effect on the kidney?
- diabetes
- amyloidosis
- goodpasture
- polyarthritis nodosa/wegener granulomatosis
- sle
what is the name/pathogenesis/morphology of Diabetic nephropathy?
Diabetic glomerular sclerosis:
non-enzymatic glycosylation of the basement membrane allows protein leakage, which precipitates to form hyalinic arteriolosclerosis. The wall thickens, lumen shrinks.
Efferent arteriole more affected than afferent arteriole -> high filtration pressure -> albuminuria
Glomerulosclerosis develops with sclerosis of mesangium. Diffuse (all glomeruli) and nodular focal (segmental) sclerosis. Kimmelstiel-Wilson Nodules.
amyloidosis deposits where?
basement membrane and mesangium
note: Matolcsy highlighted that corticosteroids worsen the symptoms
how does SLE effect the kidney? what are the 5 types called?
SLE causes a deposition of DNA and anti-DNA complexes within the glomeruli that causes inflam and eventually the proliferation of endothelial, masangial and epithelial cells (type III HS rxn)
class 1 - normal class 2 - mesangial lupus GN class 3 - focal proliferative GN class 4 - diffuse proliferative GN class 5 - membranous GN
no more fucking difficult members
What are the 6 most important diseases of nephrotic syndrome, but grouped into pairs so you can think about their differences more closely?
- Minimal Change Disease (MCD) vs Focal Segmental Glomerulosclerosis (FSGS). MCD responds better to steroids, better prognosis, more clear etiology.
- Membranous Nephropathy versus Membranoproliferative Nephropathy. MN has subepithelial deposits/ “spike and dome”, while MG has subendothelial (type I) or basement membrane (type II) deposits and “wire loop” / “tram track” appearance
- Diabetes Mellitus versus Amyloidosis: both systemic disorders. DM: hyalinic arteriolosclerosis, glomerulosclerosis, Kimmelstiel-Wilson nodules. Amyloidosis: deposits in mesangium
How do you categorize the membranous nephropathies based on the location of their immune complex deposits?
- Subendothelium deposits: Type I MPGN
- Deposits within basement membrane: Type II MPGN
- Subepithelium deposits: Membranous Nephropathy
