renal robbins Flashcards
simple facts, definitions
the study of kidney diseases is facilitated by dividing them into those that affect the four basic basic morphological components,
glomeruli, tubules, interstitium, and blood vessels
most glomerular diseases are ___ mediated, whereas tubular and interstitial disorders are frequently caused by ___
immunologically, toxic or infectious agents
azotemia
a biochemical abnormality that refers to an elevation of blood urea nitrogen(BUN) and creatitine levels, and is related largely to a decreased glomerular filtration rate(GFR). manifestation of acute or chronic kidney injury
prerenal azotemia
when there is hypoperfusion of the kidneys(hemorrhage, hypotensive shock, voume depeltion of any cause that impairs renal function in the absence of primary renal paryenchymal damage, like CHF, liver cirrhosis)
postrenal azotemia
seen whenever urine flow is obstructed distal to the kidney. removal of obstruction corrects the azotemia
uremia
azotemia plus a constellation of clinical findings and biochemical abnormalities resulting from renal damage. secondary involvements of GI, peripheral nerves, heart(fibrinous pericarditis). table 20-1
nephritic syndrome(basic def)
due to glomerular disease, presents with either visible hematuria or microscopic hematuria with dysmorphic red cells and red cell casts on urinalysis. diminished gfr, mild to moderate proteinuria, and hypertension
nephrotic syndrome(basic def)
also due to glomerular disease, heavy proteinuria more than 3.5 g a day, hypoalbuminea, severe adema, hyperlipidemia, and lipiduria (lipid in the urine)
asymptomatic hematuria or proteinuria
another manifestation of kidney pathology
acute kidney injury
rapid decline in GFR(hours or days), most severe forms exhibit oliguria or anuria(reduced urine flow), can result from glomerular, insterstitial, vascuar, or tubular injury, dysregulation of fluid electrolyte balance and waste retention of urea and creatinine. can be reversible or progress to CKD
chronic kidney disease(CKD)
chronic renal failure, mild, clinically silent, diminshed gfr less than 60ml/minute/1.73m^2 for at least 3 months or persistend albuminuria, CKD is irreversible. end result of all chronic renal parenchymal diseases
end stage renal disease(ESRD)
GFR is less than 5 percent of normal, end stage of uremia
rapidly progressive glomerulonephritis
signs of nephritic syndrome with rapid decline in GFR. implies severe glomerular injury
isolated urinary abnormalities
glomerular hematuria and/or subnephrotic proteinuria
difference between primary and secondary glomerular disease
primary stems from the kidney itself, secondary: diabetes, sle, vasculitis, amyloidosis(table 20-2)
what is the most common cause of CRF/ESRD
diabetes. hypertension is second. also lupus
describe the pthwy of filtration from the capillary to the urinary space
fenestrated endothelium, GBM-lamina rara interna, lamina densa(electron dense), lamina rara externa, podocyte filtration slits
what kind of collagen is the gbm made of
4
what does goodpasture syndrome/anti-gbm ab attach to
noncollagenous regions of collagen type 4
mesangial cells
lie between the capillaries, embedded in mesangial matrix, they are contractile, phagocytic, and capable of proliferation, laying down matrix and collagen and secrete biologically active mediators. important in many forms of glomerulonephritis
what can pass through the glomerular filtration barrier
small and cationic. albumin is large and negatively charged
visceral epithelial cell
podocyte. slit diaphragm presents a size selective diffusion barrier to the filtration of proteins, synthesizes gbm components. slit diaphragms are inbetween foot processes. again, size elective diffusion barrier to proteins. damage to these results in proteinuria
what are the four basic tissue responses to injury
hypercellularity, basement membrane thickening, hyalinosis and sclerosis,
hypercellularity
increase in the number of cells in the glomerular tufts. results from one or more of the following: proliferation of mesangial or endothelial cells. infiltration of leukocytes, and that along with with swelling and proliferation of mesangial and/or endothelial cells, called endocapillary proliferation. formation of crescents
crescents formation
proliferation of epithelial cells, mostly parietal, infiltrating leukocytes, after immune/inflammatory injury involving capillary walls, plasma proteins leak into urinary space, fibrin deposition
hyalinosis
accumulation of homogenous, eosiniphilic material, amorphous, extracellular. usually a consequence of endothelial or capillary wall injury, and is typically the end result of various forms of glomerular damage
sclerosis
deposition of extracellular collagenous matrix. may also result in obliteration of capillary lumens in affected glomeruli.
diffuse
involving all glomeruli in the kidney
global
involves entirety of individual glomeruli
focal
involves only a fraction of glomeruli in the kidney
segmental
affecting a part of each glomerulus
mesangial
affecting mesangial regions
chronic glomerular responses to injury include
basement membrane thickening, hyalinosis, and sclerosis
membranous nephropathy
immune complexes are formed locally by ab that react with intrinsic tissue ag. also, heymann nephritis. reacts to pla2r, which is a protein in glomerular epithelial cell membrane. complement activation and then shedding of the immune aggregates form the cell surface to form characteristic deposits of immune complexes along the subepithelila aspect of the bm. granular immunoflourescence, thickened bm on light microscapy
what are some ag that can be planted in the gomerulus
cationic molecules that bind to anionic components of glomerulus, dna, other nuclear proteins
where are heymann and pla2r membranous nephropathy complexes seen
subepithelial space/epimembranous space
what immunoflourescence pattern do planted and in situ immune complex membranous nephritis have?
granular
what pattern does anti gbm have
linear
what other basement membranes do anti gbm abs cross react with
lung alveoli, kindey lesion(goodpasture syndrome
in glomerulonephritis from deposistion of circulating immune complexes, what are examples of ag
endogenous; sle, iga nephropathy. exogenous: post strep, hepatitis,
in immune mediated glomeronephritis, what is the mechanism of injury
local inflammation, engagement of fc receptors on leukocytes, complement
membranoproliferative pattern
subendothelial
dense deposit disease
membranoproliferative glomerulonephritis II(MPGN type 2). alternative complement pthway
___ are a feature of multiple types of glomerular injury including focal and segmental gomerulosclerosis and diabetic nephropathy
loss of podocytes
once any renal disease destroys functioning nephrons and reduces gfr to ___ percent normal, progression to end stage renal failure(ESRF) proceeds at a steady rate independent of the original stimulus or activity of the underlying disease
30 to 50
two major hisotological characteristics of progressive renal damage are
FSGS and tubulointerstitial fibrosis
fsgs
focal segmental glomerulosclerosis. progressive fibrosis involving portions of some glomeruli develops after many types of renal injury and leads to proteinuria and increasing functional impairment. asoc w/ compensoatory hypertoryphy, eventually leads to total glomerular sclerosis and uremia
tubulointerstitial fibrosis
tubilar damage and interstitial inflammation, is a componenet of many acture and chronic glomerulonephritides
renal function decline is best correlated with
tubulointersitital damage rather than glomerular injury
nephritic syndrome
inflammation in the glomeruli. hematuria, red cell casts in the urine, azotemia, oliguria, and mild to moderate hypertension
acute proliferative comerulonephritis
includes poststrep, postinfectious. characterized histologically by diffuse proliferation of glomerular cells associated with influx of leukocytes. typically caused by immune complexes
poststrep glomerulonephritis
1 to 4 weeks after a strep infection or the skin or pharynx. assoc with overcrowding and poor hygiene. typically age 6 to 10. fomred by immune complexes containing strep ag and ab formed in situ. subpepithelial HUMP LIKE DEPOSITS. granular deposits of igg, igm, c3 in the mesangium and bm. neutrophil in lumen. enlarged glomeruli, marked hypercellularity with proliferation of endothelial and mesangial cells, leukocyte infiltration, crescent formation in severe cases
what is the clinical for post strep glomerulonephritis
slide 95/96
rpgn
rapidly progressing crescentic glomerulonephritis. syndrome assoc with severe glomerular injury, but does not denote a specific etiology. severe oliguria, nephritic syndrome. can lead to death from renal failure within weeks to months. The most common histological feature is crescents. proliferation of parietal epithelial, and infiltration of monocytes and macr.
what are the three types of rpgn
anti gbm, immune complex deposition, pauci immune
what is the hla haplotype assoc with goodpasture/rpgn
drb1`
what is the morphology of rpgn
crescents, ruptures in the gbm, blood cell leaking through bm, wrinkling of glomerular bm,
nephrotic syndrome
derangement in glomerular capillary walls resulting in increased permeablility to plasma proteins. manifestations: massive proteinuria, loss of 3.5 g or more, hypoalbuminemia, generalized edema, hyperlipidemia and lipiduria
highly selective proteinuria
low weight proteins, like albumin
membranous nephropathy
diffusie thickening of the glomerular capillary wall due to the accumulation of deposits containing ig along the subepithelial side of the basement membrane
what are some causes of membranous nephropathy
drugs nsaids, malignat tumors, lung colon carcinoma, sle, infections, hla dq1
what is the morphology of membranous nephropathy
uniform, diffuse thickening of the glomerular capillary wall without increase in cells. irregular spikes seen with silver stain,
mcg
minimal change disease. benign, uniform and diffuse effacement of foot processes, detectable only by electron microscopy. most frequent cause of nephortic syndrome in children. between 2 to 6. increased incidence with atopic disorders, hodgkins lymphoma. fusion of foot processes. normal glomeruli + effaced foot processes =mcg. lipoid nephrosis. highly selective massive proteinuria, mostly albumin. most patients respond to corticosteroids
fsgs
most common cause of nephrotic syndrome in adults in the US. hypertension, microscopic hematuria, azotemia
what is the hallmark of fsgs
effacement of foot processes
mpgn
pattern of immune mediated injury rather than a disease. type 1: deposition of immune complexes containing igg and complement. type 2: dense deposit disease. c3 glomerulopathy
