Renal Pathology Lecture III Flashcards
What happens in diseases of tubules and interstitium?
- -Ischemic or toxic injury to tubules (Leads to acute tubular necrosis, acute tubular injury and ARF)
- -Inflammatory reactions of the tubules and interstitium leading to tubulointerstitial nephritis
Acute tubular necrosis/acute tubular injury (ATN/ATI)
- -Destruction of tubular epithelial cells
- -Most common cause of ARF
- -Reversible renal lesion
ATN patterns (2 types)
- Ischemic
2. Nephrotoxic
Ischemic ATN pattern of ATN
- -Period of inadequate blood flow to kidneys, usually related to marked hypotension and shock.
- -Hemolysis, mismatched blood transfusions, skeletal muscle destruction also cause this pattern
Nephrotoxic pattern of ATN
Drugs, heavy metals, organic solvents, contrast dye
Pathogenesis of ATN
- -Same in nephrotoxic and ischemic patterns
- -Tubular injury, changes in blood flow
Tubular epithelial cell injury types
- -Reversible: cell swelling, loss of polarity
- -Lethal: necrosis and apoptosis
Disturbances in blood flow leads to what?
Intrarenal vascoconstriction (Decreased glom plasma flow and oxygen to thick ascending limb and straight segment of proximal tubule
Tubular cell injury mechanism
- -Depletion of ATP, increased intracellular Ca+++, redistribution of proteins, abnormal ion transport
- -Injured cells recruit WBCs
- -Luminal tubule obstruction by detached cells (increased intratubular P and decreased GFR)
Vasoconstrictor pathways
- Renin-angiotensin
2. Endothelin release by damaged endothelial cells with decreased NO
Recovery of ATN
- -Patchiness of tubular necrosis and intact BM allow for repair
- -Reversibly injured epithelial cells proliferate and differentiate
Pathology of ATN
- -Epithelial necrosis
- -Sloughing of tubular cells into lumen
- -Hyaline and granular casts
- -Interstitial edema and increased lymphocytes
- -Toxic ATN may show specific changes
Ethylene glycol changes in tubular lumen
Ca++ oxalate crystals
3 clinical phases of ATN
- Initiation
- Maintenance
- Recovery
Initiation of ATN
- -Slight decline in urine output
- -Increased BUN
- -Lasts about 36 hrs
Maintenance of ATN
- -Oliguria
- -Salt and water overload
- -Increased BUN
- -Hyperkalemia
- -Metabolic acidosis
- -Often need dialysis
Recovery of ATN
- -Steady increase in urine vol.
- -Can cause HYPOkalemia
- -Prognosis: 95% recovery if survives initial event
- -Related to shock/multi-organ failure has 50% mortality
Tubulointerstitial Nephritis
- -Acute and chronic forms
- -Acute: PMNs/Eos, edema
- -Chronic: fibrosis and tubular atrophy
- -Clinical: polyuria, nocturia, metabolic acidosis
- -No or mild glomerular and vascular changes (until advanced disease)
Vesicoureteral reflux
- -Incompetence of vesicoureteral valve that allows bacteria to enter ureter and renal pelvis
- -Usually due to congenital shortening of intravesicle portion of ureter
- -Bladder infection, spinal cord injury increases reflux
Morphology of acute pyelonephritis
- -Interstitial supperative inflammation (PMNs)
- -Intratubular aggregates of neutrophils
- -Tubular necrosis
- -Heals by scarring (tubular atrophy and interstitial fibrosis with lymphocytes)
- -If due to reflux, upper and lower poles of kidneys most commonly affected
Complications of acute pyelonephritis
- -Papillary necrosis (seen in diabetics and patients w/obstruction.
- -Pyonephrosis
- -Perinephric abscess
Papillary necrosis gross and micro features
Gross–yellow necrosis of papillary tips
–Micro: coagulative necrosis
Chronic pyelonephritis
- -Pelvocalyceal damage present
- -Important cause of end stage renal disease
- -Due to chronic reflux or chronic obstruction (don’t have to have bacterial infection)
Morphology of chronic pyelonephritis
- -Gross: irreg. scarred surface, discrete corticomedullary scar overlying blunted/deformed calyx
- -Micro: focal tubular atrophy w/other areas of dilated tubules (chronic interstitial inflammation and fibrosis)
Clinical course of chronic pyelonephritis
–Some patients develop focal segmental glomerulosclerosis and proteinuria
3 ways drugs can induce tubulointerstitial nephritis
- Trigger interstitial immunologic reaction
- Cause acute tubular injury/acute renal failure
- Slow injury to tubules over many years w/resulting chronic renal insufficiency
Acute drug-induced interstitial nephritis
- -Onset: About 15 days after drug exposure
- -Symptoms: fever, rash, eosinophilia, renal abnormalities
- -About 50% develop ARF (esp. in older patients)
- -Stop offending drug and majority of pts fully recover
Micro findings of acute interstitial nephritis
- -Interstitial edema and lymphocytes and macrophages
- -Variable numbers of eosinophils and PMNs
- -Granulomas and giant cells w/some drugs
- -Lymphocytes infiltrate tubular epithelium and cause variable tubular necrosis
- -Glomeruli typically normal on H and E
Pathogenesis of acute drug-induced interstitial nephritis
- -Immune response not dose related
- -Mix of type 1 (IgE related) and type 4 (delayed) hypersensitivity reactions
- -Drugs seem to act as haptens (covalently bind to cytoplasmic or extracellular component of tubular cells…elicits immune response
NSAID associated nephropathy
- -Can cause ARF, hemodynamically induced (inhibition of vasodilatory PG synthesis leads to decreased blood volume)
- -Acute hypersensitivity interstitial nephritis leading to ARF
- -Membranous GN
- -AIN and MCD
Urate nephropathy
- -Acute uric acid nephropathy due to precipitation of uric acid crystals in renal tubules leading to obstruction and ARF (classic in patients undergoing chemo)
- -Chronic urate nephropathy (associated w/gout)
- -Hypercalcemia and nephrocalcinosis
