Renal Pathology 4: Tubular Disease (Dobson) Flashcards
Two major processes that lead to AKI
- ischemic or toxic tubular injury
- inflammation of the tubules and interstitium
Acute Tubular Injury (ATI)
most common cause of AKI; damage to tubular epithelial cells and acutely diminished renal function; 50% occur in hospitalized patients reversible process; can lead to death if untreated
Ischemic ATI
due to decreased or interrupted blood flow (trauma, sepsis, shock)
Nephrotoxic ATI
may be caused by endogenous agents (gentamycin)
The two critical events of ATI
- tubular injury
- persistent and severe disturbances in blood flow
leads to decreased urine output and decreased GFR
Initiation phase of ATI
last about 36 hours, dominate by inciting medical, surgical obstetric event; ONLY indication of renal involvement is slight decline in urine output and rise in BUN
Maintenance phase of ATI
oliguric crisis; sustained decreases in urine output between 40 and 400 mL/day (oliguria), salt and water overload, rise in BUN, hyperkalemia, metabolic acidosis, and other manifestations of uremia; can overcome with tx
Recovery phase of ATI
steady increase in urine volume that may reach 3 L/day; tubules are still damaged (large amounts of water, Na+ and K+ are lost to urine) HYPOkalmeia NOT hyperkalemia becomes clinical problem
The 3 phases of ATI
- Initiation phase: 36 hrs, slight decline in urine output
- Maintenance phase: oliguric crisis; HYPERkalemia
- Recovery phase: increase in urine output; HYPOkalemia
How are tubulointerstitial disorders distinguished clinically from glomerular diseases?
- Absence of nephritic and nephrotic syndrome
- Presence of defects in tubular function, evidence of polyuria or nocturia, salt wasting; diminished ability to excrete acids (metabolic acidosis); isolated defects in tubular reabsorption and secretion
Pyelonephritis
inflammation of affecting tubules, interstitium, and renal pelvis. Two forms: acute and chronic
Acute Pyelonephritis
suppurative inflammation involving kidneys; generally caused by bacterial infection and associated with UTI
Chronic Pyelonephritis
more complex; bacterial infections play dominant role but other factors (VUR/obstruction) predispose to repeat episodes
How do the infectious organisms make it to the kidneys in Pyelonephritis?
hematogenous infection (Staphylococcus or E. coli) renal a. to kidneys OR UTI (E. coli) bacteria enters bladder, goes passed the vesicoureteral junction, then the VUR into the intrarenal reflux
Clinical presentation of pyelonephritis
CVA tenderness
Systemic features (fever, elevated WBC)
Dysuria, frequency, urgency
Associations to pyelonephritis?
Urinary tract obstruction
Instrumentation
VUR
Pregnancy
Gender and age
Preexisting renal lesions
Diabetes
Immunodefiency
How can uncomplicated E. coli cystitis be treated?
Single dose of Fosfomycin or 3 day course of TMP/SMZ or nitrofurantoin
Viral pathogen that can cause pyelonephritis?
Polyomavirus; kidney allografts (renal transplants); nuclear enlargement and intranuclear inclusions visible by LM in tubular epithelial cells
What are 3 complications of pyelonephritis?
- Papillary necrosis
- Pyonephrosis
- Perinephric abscess
Papillary necrosis
mainly bilaterally; mainly diabetics, sickle cell disease, and those in urinary tract obstruction; pyramids have gray-white to yellow necrosis (coagulative) with preservation of the tubules.
Pyonephrosis
total or almost complete obstruction in the urinary tract; suppurative exudate is unable to drain and fills the renal pelvis, calyces, and ureter with pus
Perinephric abscess
extension of suppurative inflammation through the renal capsule into the perinephric tissue
Why is Pelvocalyceal damage is an important diagnostic clue?
Because ONLY chronic pyelonephritis and analgesic nephropathy affects the renal calyces
Uncomplicated UTI caused by Proteus mirabilis treatment?
3 day course of TMP/SMZ or an oral fluoroquinolones (ciprofloxacin); complicated UTI antibiotics for 10 to 21 days
Toxins and drugs can injure kidneys is what 3 ways?
- trigger an interstitial reaction, exemplified by the acute hypersensitivity nephritis induced drugs such as methicillin
- cause ATI
- cause subclinical but cumulative injury to tubules (may be unrecognized until the renal damage is irreversible)
Clinical presentation of drug-induced interstitial nephritis
fever, eosinophilia (transient), rash and renal abnormalities. a rise in Cr and AKI with oliguria develops in 50% of pts. Treatment: stop offending drugs
Urate nephropathy
pts with hyperuricemic disorders (gout); acute - uric acid crystals in renal tubules; chronic - gouty nephropathy
Autosomal Dominant Tubulointerstitial Kidney Disease (ADTKD)
formerly known as medullary cystic kidney disease; pathogenic mechanism are unknown; distinctive mutations: MUC1, UMOD, REN, HNF1B
Distinctive mutations in Autosomal Dominant Tubulointerstitial Kidney Disease (ADTKD)? (4)
- MUC1 - mucin 1
- UMOD - uromodulin
- REN - preprorenin
- HNF1B - hepatocyte nuclear factor 1B
Muliple myeloma
causes overt renal insufficiency; Bence-Jones proteinuria and nephropathy, amyloidosis of AL, light chain deposition disease, hypercalcemia and hyperuricemia
Uromodulin
AKA Tamm-Horsfall Protein (THP); multifunctional protein in kidneys critical for modulating urinary and systemic homestasis
Hepatorenal syndrome
form of renal failure occurring individuals with liver failure in whom there is no intrinsic morphologic or functional cause of kidney dysfxn
Morphology of Ischemic ATI
focal tubular epithelial cell necrosis and BM eruption with large skip areas of unaffected tubule
Morphology of Nephrotoxic ATI
focal nonspecific necrosis especially at the straight portion of the proximal tubule and the thick ascending limb
Dirty Brown Granular cast
AKA renal failure cells are diagnostic for ATN
Mycobacterium
can cause caseating granulomatous inflammation in the urinary tract.
