Tubulointerstitial Diseases Flashcards by Matthew Miller

What are tubulointerstitial diseases?

Heterogenous disorders with tubular intersitial injury, includes acute tubular necrosis/injury, and acute or chronic tubulointerstitial nephritis

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What is the most common cause of acute renal failure?

Acute tubular necrosis / acute tubular injury

ATN / ATI

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What are the two broad etiologies of ATN/ATI?

Ischemic

Nephrotoxic

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What occurs in the pathogenesis of ATN/ATI? Is the damage irreversible?

Cells become injured and lose their functions. They are sloughed off and form necrotic plugs (brown, granular casts). Furthermore, loss of cell polarity leads to increased Na+ reabsorption in PCT -> increased Na delivery to macula densa -> further vasoconstriction of afferent arteriole and ischemia.

They may be regenerated if basement membrane stays intact.

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What do the cells look like in mild vs severe cases of ATN/ATI?

Mild - reversible changes - cellular swelling, loss of brush border and polarity, blebbing, cell detachment

Severe- irreversible changes - necrosis of cells which slough into the lumen, leaving bare basement membranes

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Give the causes of ATN/ATI within the ischemic category.

hypotension, shock, sepsis, hemorrhage, or heart failure

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Give the causes of ATN/ATI within the nephrotoxic category.

Exogenous: aminoglycosides**, heavy metals like lead, cisplatin, ethylene glycol, radiocontrast agents.

Endogenous: myoglobinuria (crush injury), hemoglobinuria, monoclonal light chains (Bence-Jones protein), urate

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What are the different patterns of damage between ischemic type vs toxic type ATN/ATI?

Ischemic - focal / patch necrosis, especially affecting proximal tubules, and TALH

Toxic type - far more diffuse damage to same areas

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What is tubulointerstitial nephritis / what are its two forms?

Renal diseases characterizes by inflammatory injury to renal tubules and interstitium, typically sparing the glomerulus

Acute form - generally reversible
Chronic form - generally progressive insults that lead to atrophy and fibrosis over years

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What are the typical causes of acute tubulointerstitial nephritis (ATIN)?

Drug reaction - penicillins, sulfa drugs (TMP/SMX, thiazide/loop diuretics, NSAIDs, proton pump inhibitors)

Systemic infections - i.e. mycoplasma

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What is the pathogenesis of drug-related acute tubulointerstitial nephritis (acute intersitial nephritis)?

Drug acts as a hapten to illicit an immune response / hypersensitivity (probably Type I / IV)

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What will ATIN show pathologically?

All the signs of a Type I/IV hypersensitivity in the interstitium and tubules

Lymphocytes, macrophages, eosinophils** (most characteristic of drug hyperreactivity), neutrophils

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What are the clinical features of ATIN?

About 15 days after drug exposure, patient has fever, rash, eosinophilia, pyuria, and hematuria.

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What is the prognosis of ATIN?

Resolves with cessation of the drug, but may progress to renal papillary necrosis

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What are the metabolic and electrolyte changes most characteristic of kidney failure (tubular issue)?

Metabolic acidosis - continued production of acids which cannot be excreted

Hyperkalemia - inability to secrete potassium in the DCT

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What is chronic tubulointersitial fibrosis (CTIN)?

Chronic tubular insults over years causing interstitial inflammation and fibrosis, and tubular atrophy with dysfunction.

Gradual loss of renal function over years.

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What causes chronic tubulointersitial fibrosis (CTIN)?

Infections, reflux or obstructive nephropathy, autoimmune disorders (SLE, Sjogren’s syndrome, sarcoidosis), metabolic diseases, chronic toxin exposures

What does it mean when CTIN is symmetric and bilateral?

CTIN is most often due to metabolic nephropathies or toxins - i.e. drugs, heavy metals, or chronic exposure to uric acid / oxalate crystals

-> will affect both sides equally

What is reflux or obstructive nephropathy?

Reflux nephropathy - damage caused by prolonged vesicoureteral reflux -> recurrent acute pyelonephritis infections

Obstructive nephropathy - chronic urinary tract obstruction leads to urine buildup and damage (i.e. due to kidney stones, BPH, or cervical carcinoma)

What is the cause of unequal or unilateral CTIN?

Diseases which can affect one side only: reflux nephropathy or chronic urinary tract obstruction

What is seen in urinary sediment in ATIN vs glomerulonephritis?

ATIN - eosinophils

GN - RBC’s and RBC casts

What are the common causative organisms of most bacterial UTIs?

E. coli, most common

Staphylococcus saphrophyticus, in sexual active young women

Proteus, Klebsiella, enterobacter

What tends to be the cause of UTIs in immunocompromised patients, especially if transplant recipients?

Adenovirus - hemorrhagic cystitis

BK virus, a polyomavirus - hemorrhagic cystitis

CMV

What are the clinical features of a cystitis?

Suprapubic pain, dysuria, frequency, urgency, with systemic symptoms usually absent

What do urinalysis, dipstick, and culture show for bacterial cystitis?

urinalysis - >10 WBC/hpf, with urine often cloudy dipstick - leukocyte esterase and nitrite positive (bacterial) Culture - >100,000 CFU / mL

What are the two broad routes of infection for acute pyelonephritis, and which is most common?

1. Hematogenous - i.e. bacteremia in septic patients, or infected emboli from endocarditis 2. Ascending infection - 95% of cases -> colonization of urethra / bladder with ascend up ureter

What are some conditions which increase the risk of UTI becoming acute pyelonephritis?

1. Obstruction of urine flow at any level - BPH, neurogenic bladder in diabetes, urethral stricture 2. Vesicoureteral reflux 3. Instrumentation of GU tract / indwelling catheter 4. Pregnancy - gravid uterus obstructs one or both ureters 5. Immune dysfunction states - AIDS, diabetes, steroids 6. Age and sex

What are the clinical features of acute pyelonephritis?

Flank pain and fever, with lab findings similar to cystitis, as well as systemic leukocytosis (systemic findings)

Who tends to get the most UTI's before age 1? Why?

Males - because congenital anomalies of urinary tract are more frequent in male infants, with problems of urethral valves and ureteral valves.

Who tends to get the most UTI's between ages 1-50 years old and why?

Women - short urethra, lack of antibacterial prostatic secretions, and trauma during sexual intercourse "honeymoon cystitis"

Who tends to get UTI's over age 50 years?

Men once again - due to benign prostatic hyperplasia -> urinary stasis

What are the possible structural underlying causes of vesicoureteral reflux?

1. Deficiency in longitudinal muscle of the ureter which causes ureter to enter bladder without sufficient tunneling -> does not close during detrussor contraction 2. Congenital para-ureteral diverticulum -> dilatation disallows bladder contraction 3. Inflammation of bladder wall, making it stiff.

How does acute pyelonephritis appear grossly?

Streaks of yellow pus extending up from the renal pyramids and medulla into the cortex -> affects the cortex, with gray-white abscesses

What does acute pyelonephritis look like microscopically / what is spared?

Intense neutrophilic interstitial / tubular infiltrate, with marked tubular destruction -> glomeruli and vessels are relatively spared

Who does Candida albicans cause UTI of?

Diabetic and immunosuppressed patients

What are the possible complications of acute pyelonephritis (other than chronic pyelonephritis due to repeated episodes)?

1. Renal papillary necrosis - sloughing off into renal pelvis, causing further obstruction 2. Perinephric abscess - infection breaking through renal capsule and spreading to perinephric soft tissues 3. Pyonephrosis - infection is so severe kidney is literally transformed into a bag of pus 4. Urosepsis - bloodstream infection

How does renal papillary necrosis appear pathologically?

Coagulation necrosis (ischemic) with sharply demarcated edges undergiong inflammation

What is the cause of chronic pyelonephritis and how does it appear grossly?

Repeated bouts of acute pyelonephritis Appears as severe scarring of renal parenchyma, calyces, and pelvis. This leads to **blunted calyces**. Cortex will be thinned by numerous broad scars

What are the underlying conditions which predispose to chronic pyelonephritis? What will intrarenal reflux cause?

Vesicoureteral reflux and chronic obstructing kidney stones. Intrarenal reflux caused by very bad vesicoureteral reflux will cause scarring at upper and lower poles of the kidney.

How will chronic pyelonephritis appear microscopically?

Tubules contain eosinophilic casts resembling thyroid tissue -> **thyroidization of tubules.** Everything else will be scarred and fibrosed -> glomerulosclerosis and interstitial fibrosis, with tubular atrophy (obviously)