Dz of tubules & interstitium Flashcards
What are the 2 major mechanisms of tubulointerstitial dz?
- Ishcemic/toxic = non-inflammatory
- ATN - Inflammatory
- tubulointerstitial nephritis: infection, allergic/drug induced, systemic dz
How can you tell if renal failure is acute or chronic?
Based on the history
But also based on ultrasound of kidneys: if they’re shrunken, it’s chronic
What are the 3 major categories of acute renal failure?
- Prerenal azotemia
- Postrenal azotemia
- Intrinsic renal failure: ATN, AIN, AGN, vascular
ATN=acute tubular necrosis
AIN= acute interstitial nephritis
AGN= acute glomerulonephritis
Why are the tubular epithelial cells more predisposed to acute injury?
High metabolic activity & O2 requirements –> prone to ischemic/hypoxic injury
Role in concentrating/reabsorbing filtrate –> increased exposure to toxins
This is why the proximal tubule is even more prone to injury!
ATN: what is it?
Physiologic syndrome (not morphologic: sometimes you see very lilttle damage morphologically)
Classic oliguric and diuretic phases
Sometimes non-oliguric ATN can be seen with nephrotoxic
What are the clinical phases of ATN?
- initiation: first 36 hours, dominated by initial event
-
maintenance: oliguric, requires dialysis, up to 3 weeks; tubules don’t work but they start regenerating
- tubular epithelial cells are flat, you dont see acute necrosis anymore -
recovery: diuretic phase = increasing urine output, often substantial, electrolyte abnormalities
- you filter so you make too much urine bc you can filter but you can’t reabsorb -
prognosis: 90% recovery if survive initiating event
- tubules are fully restored
2 subtypes of ATN:
Ischemic
Nephrotoxic
ATN: histological/pathological findings?
Brown muddy casts in urine & on biopsy
In the tubule, sloughed off cells, loss of brush border
If it’s myoglobinurea ATN, due to muscle damage, kidneys are grossly more brown
Ischemic ATN: associated with what conditions? pathological changes?
Occurs in setting of decreased renal blood flow/ hypotension i.e. trauma, severe blood loss, CHF
- *Pathology**:
- gross P&S: pale and swollen
- degenerative changes
- subsequent regenerative changes
- most severe changes in proximal tubule and mTAL
Nephrotixic ATN: what toxins implicated?
Heavy metals
Organic solvents
Therapeutics:
What is the pathology of ischemic ATN?
Similar pathology to ischemic ATN
Additional toxin-specific findings:
- *ethylene glycol** (oxalate precipitation)
- *osmotic agents**/radiocontrast – swollen tubules,
- *light chains** (plasma cells make light chains, so if you have a malignancy of light chains leads to synthesis of tons of light chains and Ig’s –> tubule has giant cells and crystals)
- *hemoglobin/myoglobin**
If you suspect ATN, should you biopsy?
For ATN: NO, because it often resolves on its own! Having a biopsy doesn’t help you in your treatment
For the other causes of acute injury, YES, you need to biopsy because the treatments are different for vascular, AIN, AGN
Acute interstitial nephritis- what is it?
Cell-mediated hypersensitivity reaction (T cells), usually to medications
Interstitial inflammation & edema
Eosinophils
Tubulitis
+/- granulomas
Which medications can cause AIN?
Beta lactam antibiotics
Other antibiotics: sulfonamides, tm-smx, rifampin, quinolones
Diuretics (rarely)
NSAIDS (rarely)
Other drugs- cimetidine, dilantin, sulfinpyrazone, allopurinal
Proton pump inhibitors
What are the clinical findings of AIN? i.e. they hypersnesitivity triad
Rash
Fever
Eosinophilia
Urinary findings in AIN?
Mild proteinurea
Hematuria
Sterile pyuria
Eosinophiluria
Treatment of AIN? Course?
Discontinue all meds, use alternatives
Prednisone 120 mg every other day x 6 weeks
Plasma creat decreased to a much better but not optimal level, stable RFTs 4 years later
What is pyelonephritis?
Inflammation of the pelvis of the kidney
Can be acute or chronic
What are the pathological findings of pyelonephritis?
WBC casts in urine and on biopsy
Diffuse inflammation
Abscesses on autopsy: replacement of parenchyma with microabscesses
What is acute pyelonephritis? Clinical presentation? Route of infection? Organisms?
Acute suppurative (pus-forming) infection of the kidney
Clinical: back pain, fever, pyuria (pus)
- urine cultures to confirm & to check antibiotic sensitivity
Route of infection:
- ascending > hematogenous
- ascending starts in bladder as UTI, more common in females
- hematogenous = from septic emboli, bacteremia
Organisms: mostly gram neg bacilli, #1 is E. coli, mostly from fecal flora
What increases the risk of acute pyelonephritis?
Obstruction: BPH, tumors, pregnancy, neurogenic bladder
Instrumentation
- *Vesicoureteral reflux**: major cause of pyelo in infants
- congenital anomaly: intravesical portion of ureter lacks normal oblique course that prevents reflux
- when you contract your bladder, instead of the bladder wall closing, it remains open which means that the urine goes back up
What are teh pathological findings of acute pyelonephritis?
Normal size +/- coalescent abscesses
Severe inflammation, PMNs, microabscesses, PMN casts & tubulitis
If it’s ascending, originates near medulla
If it’s hematogenous, cortical
What is acute pyelonephritis? What are the findings?
Chronic renal disorder w scarring, inflammation, and deformity of calyces/pelvis (ascending)
Gross: shrunken
- irregular, asymmetric broad/flat scars- U-shaped
- papillary blunting and calyceal deformity
Micro: disproportionate tubulointerstitial scarring
atrophic tubules with colloid casts (thyroidization)
chronic inflammation, not PMNs
Whats the clinical presentation of chronic pyelonephritis?
Insidious onset of RI
+/- htn, mild proteinuria, decreased urinary concentration, culture neg
Rarely follows usual acute pyelo
More common with persistent obstruction or VUR
+/- awareness of acute episodes
What’s the treatment of chronic pyelo?
Relieve obstsruction
Correct VUR
Antibiotics as indicated
Thyroidization
Common in chronic pyelo
atrophic tubules with colloid casts
What’s a voiding cystourethrogram?
Done in children who have pyelo to see if they have VUR
Put contrast in the bladder
Take an xray
Normal: it will go right back out
In vesicoureteral reflux (VUR), you get massively dilated ureters and the contrast fills up all the way to the kidneys
What is papillary necrosis?
Necrotic papillae
Renal abnormalities: sterile pyuria
mild proteinuria & htn
decreased concentration ability of the kidneys
decreased net acid excretion
salt wasting
papillary necrosis
What are the 4 major causes of papillary necrosis?
SODA:
- *S**ickle cell anemia
- medulla leads to sickling
- sickling leads to medullary ischemia
Obstructive pyelonephritis
Diabetes mellitus
- *A**nalgesic abuse
- increased risk with combinations
- direct toxicity & ASA-induced PG deficiency
What types of renal dz can you see from NSAIDS? 4 major ones
AIN
ATN
Papillary necrosis
Minimal change dz (rarely membranous glomerulopathy)
