01-09 PATH: Tubulointerstitial Dzs Flashcards
osmotic nephrosis
- cause?
- path?
- course?
“reversible renal tubular injury most often seen following administration of agents used to induce an osmotic diuresis.”
Cause: hypertonic sol’ns, IVIg, IV contrast
Path: Distention of phagolysosomes → diffuse vaculolar ∆s, esp in PCT
Course: Revsersible w/in 6 hrs
Hyaline Droplet Change
proteinuria/nephrotic syndrome → incr tubular [prot] → protein resorption droplets in PT epithel
Acute Kidney Injury (Acute Tubular Injury/ATN)
—definition
—two main subtypes?
DEF: acute tubular damage that leads to ARF
—”The major forms of acute kidney injury that are due to direct tubular injury are ischemic and toxic. The proximal tubule is most susceptible to this form of injury. When the injury is severe enough to cause necrosis of tubular cells, it may be termed acute tubular necrosis.”
TYPES: 1. ischemic AKI 2. toxic AKI
Define ARF
—Give subtypes
Acute renal failure definition: —acute ↓ GFR —olig-/an-uria —↑ BUN/Creatinine Subtypes of ARF: —pre-renal —post-renal —intra-renal incl: ——1) glomerular ——2) vascular ——3) interstitial (AIN)* ——4) tubular (AKI/ATN)* *today's lecture
Ischemic AKI —causes —clinical picture —gross path —micro path
CAUSES: usu. shock (i.e. inadeq visc BF); also crush injuries, hemo-/myo-globinuria, hepatorenal syn, sepsis
CLINICAL PICTURE: ↓ tubular fx → ↑ urine osmolality/[Na+] etc.; is reversible
GROSS: Swollen kidney w/ pale cortex and congested medulla, usu patchy (vs. confluent in toxic AKI)
MICRO: Affects predom the str8 portion of PT and ThAL
• distalization of PT - dilate, flat, lose brush
• necrosis w/ denud’d BM
• granular hyaline casts
• interstitial edema
• regen ∆s of tubular epithelium
Possible Mechanisms by which AKI can → ARF
MAIN: ATN → ↓ GFR → ↑ BUN/Cr
• Backleak of filtered fluid through damaged tubule wall → ↑ interstitial pressure → collapse of tubule
• Tubular obstruction by casts & necrotic cells → ↑ tubular lumen pressure → ↓ glomerular transcapillary pressure
• Arteriolar vasoconstriction ↓ ∆P during filtration → ↓ GFR (2° to renin release ?)
• Direct glomerular effect?
Toxic AKI
—causes
—micro path
—Why tubules so sensitive?
CAUSES: drugs/meds; can be via direct cytotoxicity, hypersensitivity or ischemia
MICRO: diffuse hypereosinophilia (redness); Usu most involves PT, but also DT; more confuent along tubulethan ischemic’s patchy pattern
SENSITIVITY:
• high % of C.O. directed to the kidney
• high conc of filtered toxins
• tubular epithelium vulnerable b/c of high energy consumption
Clinical Course of AKI/ATN
Initiating phase -- 1-2 days - mild ↓ in urine output (vs. TIN w/ polyuria) Maintenance phase - sustained ↓ in urine output (40 - 400 ml/day) - salt and H2O overload - ↑ BUN and K+ - metabolic acidosis Recovery phase - ↑ing urine output (> 3 L/day) - ↓ing K+, BUN, creatinine
tubulointerstitial dz
—mechs behind major clinical manifestations
—main classes
Clinical manifestations predominantly relate to defects in tubular function:
• ↓ conc →polyuria (vs. AKI w/ oliguria)
• ↓ salt reabs →Na+ wasting
• ↓ acid excretion →metabolic acidosis
Major disease categories:
1. Pyelonephritis
2. Tubulo-interstitial nephritis (non-infectious)
Pyelonephritis
—causative organisms
—compare pathogenesis of the two categories
ORGANISMS:
— >86% Gm- rods (E. Coli, klebsiella, proteus, eneterobacter)
— also: Strep. faecalis, Staph, fungi, others
ASCENDING:
1. urethra → bladder → incomp vesico-ureteral orifice→ reflux → FOCAL colonization of compound papillae
HEMATOGENOUS:
intro via bloodstream → DIFFUSE miliary “punctate microabscesses” in kidney
Complications of acute pyelonephritis
—perinephric abscess
—pyonephrosis
—papilary necrosis (cause casts that act like stones)
—scarring
Chronic Pyelonephritis
—Path
—Two categories
—How to dx?
PATH: Tubulointerstitial inflam & scarring associated w/ path. involv. of calyces & pelvis.
CATEGORIES:
1. Obstructive - unilat or bilat
2. Non-obstructive (reflux) - most common
DX: cannot be made by light micro alone, esp. just with biopsy, b/c histo features not specific.
TIN (Tubulointerstitial nephritis) —Summary —Cause —Pathogenesis —Defining acute v. chronic
SUMMARY: Classic TIN is usually associated with fever, eosinophilia, renal tubular functional abnormalities, and oliguric acute renal failure. Present ~15 days s/p dose
CAUSE: drugs/toxins (meth-/ampicillin, rifampin, thiazides, cimetidine)
PATH: during secretion, drug is covalently bound
to cytoplasmic or extracel compon. of epithelial cells, rendering them haptens → IgE-mediated, delayed-type hypersens., damage to tubular cells and TBM
—cells incl T_h, M0s, and eosinophils!!
ACUTE: PMNs predom
CHRONIC: lymphs predom
Analgesic Abuse Nephropathy
—Cause
—Pathogenesis
—Path
CAUSE: phenacetin orig; ASA, APAP, caffeine
PATHOGENESIS: APAP both covalently binds & oxidates; ASA: decr prostaglandins → ischemia
PATH:
- chronic TIN and fibrosis
- papillary necrosis
- urothelial carcinoma, esp. upper tract
Urate Nephropathy
—Summary
—3 types
SUMMARY: “U.N. may be assoc w/ inflam, gouty deposits, and/or urate stones.”
3 TYPES:
1) Acute uric acid nephropathy - caused by precipitation of uric acid crystals
in collecting ducts → obstruction → ARF
- esp in cancer pts s/p chemo (lysis)
- favored by acid pH in collecting tubules
2) Chronic urate nephropathy - in patients with hyperuricemia - tophus formation
3) Nephrolithiasis (in 22% of patients with gout)
