Renal 5 Flashcards
examples of interstitial disease
ischemic papillary necrosis, toxic and HS (drugs)
most common cause of intrinsic renal disease and ARF
ATN
two most common causes of ATN
acute toxic or ischemic damage (loss blood flow)
this combination depicts spectrum of symptoms present in ATN
loss tubular function and GFR
what occurs due to toxic or ischemic damage of tubules
acute necrosis of tubular epithelium with acute suppression renal function
what occurs intracellularly due to tubular ischemic injury
depletion ATP, accumulation Ca, activation proteases and phospholipases
morphology of ATN (regardless of etiology)
focal tubular epithelial necrosis/apoptosis, rupture BM, occlusion tubular lumens by casts
part of tubule most commonly injured by toxins
proximal segment
toxicity of carbon tetrachloride is characterized by this
neutral lipid accumulation
characterizes ethylene glycol poisoning of kidney
ballooning and hydropic or vacuolar degeneration w/ formation calcium oxalate crystals
what occurs in initiating phase of ATN
declining urine output, increasing BUN (36 hours)
what occurs in recovery phase of ATN
increase urine output (3 L/day), hypokalemia, gradual improvement concentrating ability
what occurs in maintenance phase of ATN (several days)
diminished renal output, salt and water overload, increased BUN, hyperkalemia, metabolic acidosis (ALL FROM DECREASED GFR)
possible causes of acute interstitial nephritis
HS to drugs or metabolic dysfunction, ARF
gentimycin potentially causes this kind of kidney damage
ATN
synthetic penicillins (methicillin, ampicillin) potentially cause this kind of kidney damage
acute interstitial nephritis
drugs that are known to cause acute interstitial nephritis
sulfonamides, synthetic penicillins, diuretics (thiazides), NSAIDS (phenylbutazone)
chronic analgesic abuse is associated with development of this
transitional papillary carcinoma of renal pelvis
this is associated with development of transitional papillary carcinoma of renal pelvis
chronic analgesic abuse
causes of papillary necrosis
analgesic nephropathy, diabetes, urinary tract obstruction, sickle cell (anemia or trait), renal TB
benign renal tumor with eosinophilic cells and LOTS of mitochondria
oncocytoma
clinical presentation of Wilm’s tumor (nephroblastoma)
large abdominal mass, hematuria/pain after trauma, intestinal obstruction, HTN (damage to blood flow)
what renal cell carcinoma tumors arise from
tubular epithelium
nephrotoxic agents that can cause ATN
gentamicin, radiographic contrast agents, heavy metals, carbon tetrachloride
common scenarios that lead to ATN
transfusion reaction, ethylene glycol or methanol poisoning, hemoglobinuria or myoglobinuria (crush injury, alcohol binges), shock
ischemic changes seen in tubular cell injury
cell swelling, blebbing, loss of polarity, necrosis/apoptosis
this signals feedback mechanism to constrict afferent arteriole (decreasing delivery of filtrate) in ATN pathogenesis
increased Na in distal tubules
this complicates tubular ischemia (other than change in glomerular flow rate)
reflex vasoconstriction and decreased GFR
this determines re-epithelializatoin and return of tubule function
integrity tubular BM
this makes up casts in ATN -> huge glycoprotein secreted in loop of Henle and distal tubules
Tamm-Horsfall protein
these all contribute to cast formation in ATN (eosinophilic hyaline or pigmented granular casts)
Tamm-Horsfall protein, hemoglobin, myoglobin, plasma proteins
where Tamm-Horsfall proteins are secreted
loop of Henle and distal tubules
morphology of regenerating epithelial cells
flattened, hyperchromatic nuclei, mitotic figures
form of ATN that is usually related to non-oliguric presentation (50%)
toxic
primary cause of interstitial disease; secondary?
infection, toxin, obstruction; vascular, cystic, glomerular disease progression
this distinguishes interstitial nephritis from other renal disease
absence nephritic/nephrotic syndrome
signs of secondary tubular function defect related to interstitial disease
impaired concentrating ability, salt wasting, metabolic acidosis, isolated defect tubular reabsorption/secretion
possible cause of chronic interstitial nephritis; what is morphology?
slowly progressing toxic dysfunction (analgesic abuse); infiltration mononuclear cells, interstitial fibrosis, tubular atrophy
symptoms of HS reaction in acute drug-induced interstitial nephritis -> 2-6 weeks after exposure
fever, eosinophilia, rash (25%), renal abnormalities (ARF, increasing serum Cr)
associated condition with chronic analgesic abuse
chronic tubulointerstitial nephritis with renal papillary necrosis
this analgesic has metabolites with direct toxic effects to the kidney; how does it cause damage?
phenacetin; oxidative damage
this potentiates phenacetin oxidative injury on kidney
prostaglandin inhibitors (causes ischemia)
what occurs first in chronic analgesic abuse: papillary necrosis or tubulointerstitial nephritis?
papillary necrosis
morphology of acute HS interstitial nephritis
edema, interstitial monocyte/lymphocyte infiltrate (some PMN and eosinophil also)
these drugs cause interstitial granuloma formation
methicillin, thiazides
chronic morphological changes in interstitial nephritis
tubular atrophy, interstitial fibrosis, inflammation, surface depression, papillary necrosis/calcification/fragmentation, coagulative necrosis
signs/symptoms of analgesic nephropathy
inability concentrate urine, metabolic acidosis, stone formation, HA, anemia, GI symptoms, HTN
consequences of papillary necrosis
urinary obstruction, infection, stone formation
various mechanisms of NSAID nephropathy
lack vasodilation causing ARF, acute HS reaction, acute interstitial nephritis and lipoid nephrosis, membranous GN w/ nephrotic syndrome
consequence of hypercalcemia and nephrocalcinosis -> deposition of calcium leading to chronic tubulointerstitial disease
tubular atrophy, interstitial fibrosis and inflammation
mechanisms of interstitial fibrosis
CRF, transplant, angiotensin II (chronic activation RAS), TGF-b induction thru NFK-b
direct complications of MM tumor leading to renal disease
hypercalcemia, hyperuricemia, obstruction ureters
forms of MM related kidney disease
light-chain GN, tubular obstruction and cast nephropathy (deposition, combine with Tamm-Horsfall to make casts)
morphology of MM kidney disease
Bence Jones tubular casts, adjacent interstitial inflammation, amyloid deposits, granulomatous inflammatory rxn
MM related ARF may be precipitated by these factors
dehydration, hypercalcemia, infection, nephrotoxic antibiotics
characteristic of amyloidosis
Congo red positive fibrillary deposits in mesangium and sub endothelium, obliteration glomerulus, blood vessel walls, kidney interstitium
where are benign renal papillary adenomas found? what are they derived from?
cortex; tubular epithelium
renal papillary adenoma does not differ from this malignant cancer -> only distinguishing feature is size
low-grade papillary renal cell carcinoma
benign renal tumor in children
cystic nephroma
most common primary renal tumor of childhood (ages 2-5)
Wilm’s tumor (nephroblastoma)
inheritable syndromes of wilm’s tumor associated with this
specific aberrations multiple loci chromosome 11 (WT1 -> tumor supressor gene)
premalignant condition associated with wilm’s tumor -> multi centric or diffuse foci immature nephrogenic elements
nephroblastomatosis
found in nephroblastomatosis (premalignant) -> second genetic insult results in malignant tumor formation
immature nephrogenic elements
diagnostic morphology of Wilm’s tumor
recapitulation different stages nephrogenesis, metanephric blastemic and immature stromal/epithelial elements
this may represent precursor lesions to Wilm’s tumor
neprogenic tests
associated clinical syndrome of Wilms tumor -> WAGR
wilms tumor, aniridia, GU anomalies, mental retardation
associated clinical syndrome of Wilms tumor -> Denys-Drash syndrome (DDS)
wilms tumor, intersexual disorders, glomeruopathy
associated clinical syndrome of Wilms tumor -> Beckwith-Wiedemann syndrome (BWS)
wilms tumor, overgrowth (gigantism), visceromegaly, macroglossia
renal cell carcinoma cells resemble these
clear cells of adrenal cortex
risk factors for renal cell carcinoma
tobacco, obesity, HTN, unopposed estrogen tx, asbestos/petroleum exposure, CRF, dialysis (acquired cystic disease)
genetic abnormality associated with clear cell carcinoma (most common renal cell carcinoma)
unbalanced translocation chromosome 3 -> loss of VHL gene
what gives rise to chromophobe renal carcinoma (excellent prognosis)
intercalated cells collecting ducts
autosomal dominant cause of renal cell carcinoma -> characterized by renal cysts and bilateral renal cancer, hemangioblastomas of cerebellum and retina
Von Hippel-Lindau syndrome
genetic abnormalities in hereditary papillary carcinomas
trisomies 7, 16, 17, loss of y in male, mutation c-met protooncogen
morphology of renal cell carcinoma
upper pole (more commonly), solitary or unilateral lesion, bright yellow/gray-white, large necrotic area
where does renal cell carcinoma tend to fungate?
ureter and renal vein (thru IVC to right side of heart)
morphology of papillary tumors
multifocal or bilateral, hemorrhagic and cystic
can stain for these components in clear cell carcinoma
glycogen and lipids
morphology of clear cell carcinoma
rounded or polygonal, delicate branching vasculature, cystic or solid, glycogen and lipids
morphology of papillary carcinoma
papillary formations, cuboidal or low columnar cells, psamomma bodies
