Tubulointerstitial disease ERF 12/12/06 Quizbank: Kidney #41-53, 63-77, 173-179, 192-204, 220-240 I) Disorders of the proximal

tubule A) Congenital: Inborn errors of transport 1) Renal glycosuria 2) Renal transport aminoacidurias B) Acquired Fanconi syndrome: 1) Poisoning: lead, cadmium, bismuth, oxalate, outdated tetracycline 2) Systemic disease: Wilson’s, plasma cell myeloma Acute tubular necrosis-

II)

B) Complex pathophysiology 1) Ischemia and nephrotoxins directly damage tubules 2) Systemic hypotension and severe poisoning also cause intrarenal vasoconstriction, which compounds ischemic damage and lowers GFR 3) Damaged tubules become obstructed by casts and crud, which further lowers GFR 4) Direct glomerular damage may occur 5) Tubular backleak contributes to oliguria 6) In ATN, the renal output is normal or low; the urine is iso-osmotic with Na concentration close to that in glomerular filtrate

Higher mag
A) What you call all forms of acute renal failure caused by damage to tubular epithelial cells 1) Ischemic ATN: caused by ischemia (shock, hemorrhage, septic shock, etc). Also seen in new transplants, from contrast media, in low-output states, NSAIDs & ACE-I’s 2) Nephrotoxic ATN: caused by a wide variety of renal poisons, including heavy metals (mercury), organic solvents, or antimicrobial agents 3) Pigment nephropathy-massive hemolysis (red cell stroma plugs the tubules, ABO mismatch, falciparum malaria, et al), massive rhabdomyolisis, crush injury, lightening, cocaine, beatings, etc 4) Viral hemorrhagic fevers often cause temporary renal shutdown Low magnification: note the dilated convoluted tubules, and their necrotic epithelial walls that shed into the lumen of the tubules. Glomeruli are relatively intact.

Higher magnification view showing a normal glomerlus surrounded by necrotic tubules.

The tubular vacuolization and dilation here is a result of ethylene glycol poisoning. This is representative of acute tubular necrosis (ATN), which has many causes. ATN resulting from toxins usually has diffuse tubular involvement, whereas ATN resulting from ischemia (as in profound hypotension from cardiac failure) has patchy tubular nvolvement.

ATN

Histology reflects the pathophysiology 1) Ischemic ATN: a few necrotic cells or basement membrane may be present. Look for dilated tubules and interstitial edema. Proximal tubular cells show evidence of regeneration at all stages 2) Nephrotoxic ATN: frank necrosis is often seen, usually limited to proximal tubules, w/o rupture of basement membranes D) Clinical picture of iscehemic ATN 1) Onset during medical/surgical catastrophe 2) Oliguric stage- w/ urine production 50-400 mL/24 hours and isotonic 3) Diuretic stage- rapid loss of fluid and potassium; tubule regeneration during this stage 4) Pt will recover unless : in deep coma, has cancer, severe hypotension, or needs mechanical ventilation E) Other causes of acute renal shutdown other than ATN: 1) Atheroembolization 2) Severe rapidly progressive glomerulonephritis 3) Drug hypersensitivity 4) Vasculopathies 5) Hepatorenal syndrome 6) DIC 7) Acute urate nephropathy 8) Severe rapidly progressive glomerulonephritis III) Hepatorenal syndrome A) Kidney failure that develops in patients with liver failure, without anatomic changes in the kidney. This often follows enthusiastic administration of highpowered diuretics to a cirrhotic “to help w/ ascites” B) The pathophysiology is getting worked out 1) Liver failure from any cause produces hypotension, and “hepatorenal syndrome” may have component of “shock kidney” 2) Dilation of small arteries in the splanchnic bed and inappropriate constriction of small arteries in the kidney IV) Pyelonephritis and other upper UTI –extremely common and serious in clinical medicine A) Causes: Ascending infection (E. coli & gram negatives, common), Hematogenous infection (staph & TB, uncommon) B) Acute pyelonephritis: 1) Predisposing conditions (a) Bacterial virulence (b) Urinary obstruction/stasis (c) Mechanical factors (d) Diabetes mellitus (e) Not being circumcised (f) Pt’s sex and age (<40 females; >40 males) (g) Vesicoureteral reflux (h) Asymptomatic bacteriuria (i) Pre-existing renal dzs, especially kidney stones (j) Not urininating when you need to, not drinking enough water 2) PMN’s infiltrate the interstitium and tubules. 3) Patients have fever, pain at costovertebral angle, PMN’s and white cell casts in the urine 4) Papillary necrosis is a dreaded complication of acute pyelonephritis that occurs mostly in diabetics

C)

This is an ascending bacterial infection leading to acute pyelonephritis. Numerous PMN's are seen filling renal tubules across the center and right of this picture.

The cut surface of this kidney demonstrates many small yellowish microabscesses.

At high magnification, many neutrophils are seen in the tubules and interstitium in a case of acute pyelonephritis.

Acute pyelonephritis

C)

Chronic pyelonephritis (any chronic renal infection) 1) Look for broad U-shaped scars over distorted calyces. Scarring is most likely to be present at renal poles

Chronic pyelonephritis 3) An important cause of morbidity and mortality in the wheelchair-bound 4) Xanthogranulomatous pyelonephritis is common and usually in those who have had several episodes of acute PN (a) Caused by Proteus and a problem w/ cGMP & probably begins as a penetrating ulcer of a calyx (b) Located mostly around the pelvis, the process tends to spread and can grow out around kidney and erode the area around the kidney and produce fistulas to the groin, back or gut (c) Lipid-laden macrophages form yellow nodules that look like renal cell carcinoma grossly & microscopically

The large collection of chronic inflammatory cells here is in a patient with a history of multiple recurrent UTI. This is chronic pyelonephritis.

Both lymphocytes and plasma cells are seen at high magnification in this case of chronic pyelonephritis. It is not uncommon to see lymphocytes accompany just about any chronic renal disease: glomerulonephritis, nephrosclerosis, pyelonephritis. However, the plasma cells are most characteristic for chronic pyelonephritis.

In this specimen the renal pelvis (P) and the calyces (C) are dilated. D) Other causes include lupus and other “autoimmune” problems that generate anti-TBM antibody E) The BK polyomavirus causes a nephritis in the immunosuppressed

2)

Microscopically it is a patchy process with periglomerular fibrosis and interstitial scarring (“thyroidization”)

F)

TB of the kidney is relatively common b/c of high oxygen tensions. If there are WBC in urine & no bacteria, get a TB culture

TB of kidney V) Chronic interstitial nephritis- scarring of the kidney from a process that is primarily interstitial

interstitial nephritis A) Used to be called “chronic pyelonephritis” (which is an important cause) B) Lupus and Sjogren’s often include an acute or chronic interstitial nephritis, a minor problem C) “Granulomatous CIN” is due to drugs or sarcoid, the latter is less severe D) Anti-tubular basement membrane antibody is a research tool, but no one knows its importance VI) Tubulointerstitial nephritis caused by drugs and poison A) Acute drug-induced (hypersensitivity) nephritis 1) W/in a month after drug exposure, victim develops fever, skin rash, eosinophilia, hematuria, proteinuria, sterile pyuria, and/or eosinophiliuria. Withdrawal of drugs makes things better (a) Methicillin is best known offending drug

(b) Sulfa drugs, rifampin, cyclosporine et al are important causes 2) If biopsied, edema is present & interstitial mononuclear cell infiltration, EOS and NEUTS may be found too NOTE: The other important cause of eosinophiliuria is atheroembolization B) Analgesic nephritis 1) Chronic renal failure used to be common in those who took phenacetin-containing combinations for pain 2) Asprin, fenprovin, naproxen, phenylbutazone, indomethacin, and ibuprofen have all produced similar lesions 3) Chronic interstitial inflammation is characteristic and many patients develop papillary necrosis C) Classic non-steroidal anti-inflammatory agents 1) May be today’s most common cause of renal shutdown in outpatients 2) The prevalence reverses on removal of the offending drug, is just now being recognized D) Lithium nephropathy- mostly nephrogenic diabetes insipidus, supposedly due to fibrosis around the collecting duct E) Cyclosporine nephropathy- interstitial fibrosis seems to result from direct toxicity to tubular epithelial cells 1) Look for: (a) Hydropic change in proximal tubular cells (b) Giant mitochondria in tubular cells (c) Myxoid change in intima of small vessels (d) Tubular microcalcifications (e) Necrosis of the smooth muscle cells of blood vessels (f) Tubular atrophy and interstitial fibrosis 2) Other poisons: cadmium, lead, and bismuth VII) Hypercalcemic nephropathy- when serum potassium is very low, the kidney cannot concentrate urine VIII) Plasma cell meyloma kidney A) Precipitation of Bence-Jones proteins causes renal shutdown. Patients experience acute or insidious onset of renal failure 1) Amorphous pink casts, often surrounded by a foreign-body reaction w/ multinucleated giant cells B) Patients often get amyloidosis B IX) Oxalate nephropathy- Antifreeze drinkers, inborn errors, and extreme ascorbic acid abusers; Oxalic acid crystals ruin the kidney X) Radiation nephritis- following therapeutic radiation, interlobular arteries narrow. This eventually causes HTN and renal failure XI) Nephrogenic diabetes insipidus- collecting duct is unable to respond to ADH; could be inborn errors of metabolism or lack of ADH receptor; gross and widespread damage to the medullar occurs and late effects of lithium therapy for mania

XII) Gout PP 10-12 (happy reading)

This is gout. Gouty arthritis results from deposition of sodium urate crystals in joints. The joint most often affected is the first MP joint (big toe) as seen here. Acute attacks are characterized by severe pain, swelling, and erythema of the joint.

If synovial fluid is aspirated from a patient with gout, the fluid can be examined for the presence of sodium urate crystals, which are seen here to be needle shaped. If they are observed under polarized light with a red compensator, they appear yellow (negatively birefringent) in the main ("slow") axis of the compensator and blue in the opposite perpendicular direction.

Gout tophus