9/21- Tubular Disorders Flashcards
What is the kidney interstitial space?
Space between tubules and glomeruli containing vasculature and connective tissue cells
- May be damaged by primary disease or secondary process
- Interstitial space, tubule, and glomerulus function as a unit; damage to one component will affect others
What is seen here?
Normal kidney anatomy
- Glomerulus and Bowman’s capsule
- Tubules- (columnar epithelium)
What is seen here?
Acute changes: edema and cellular infiltrates
- Many “black dots” and “red jello”
- Top arrow = black dot with surrounding red = eosinophilia
- Can see space between tubules; edema and swelling (multicellular infiltrates between tubules)
What is seen here?
Chronic renal changes:
- Tubule dilation and degeneration
- Fibrosis
- Interstitial space (space between tubules) but without inflammatoryinfiltrate
What is seen here?
Chronic renal changes:
- Glomerulosclerosis
- Vascular sclerosis
What are urinary findings and disease examples in damage to:
- Tubule
- Interstitial space
- Urinary obstruction
- Glomerular disease
- Renal cystic disease
- Metabolic disease
Tubule
- Ex: ATN (acute tubular necrosis)
- Urine: granular casts
Interstitial space
- Ex: pyelonephritis
- Urine: WBC (neutrophils), bacteria, culture
Also IS space:
- Ex: Allergic IN
- Urine: WBC (eosinophils), (-) culture
Urinary obstruction
- Ex: BPH
- Urine: Benign urine
Glomerular disease
- Ex: Membranous GN
- Urine: Proteinuria, hematuria
Renal cystic disease
- Ex: Polycystic kidney disease
- Urine: Hematuria
Metabolic disease
- Ex: Cystinuria
- Urine: Urinary crystals
List of etiologies of interstitial diseases (don’t memorize)?
- Infections: bacterial, fungal, viral, mycobacterial
- Drugs: NSAIDS, herbals, cisplatinum, lithium, others
- Hematopoietic Diseases: sickle cell, myeloma and lymphoproliferative disorders
- Obstruction: VUR, mechanical
- Heavy Metals: lead, cadmium, etc
- Hereditary Diseases: PCKD, medullary cystic dis., hereditary nephritis, medullary sponge kidney, juvenile nephronophthisis, etc
- Metabolic Disorders: diabetes mellitus, hyperuricemia, cystinosis, K+ depletion, oxaluria, hypercalcemia
- Immunologic Diseases: SLE, Transplanted kidney, cryoglobulinemia, Sjögrens, Goodpasture
What are methods of bacterial kidney infection (spread)?
- Systemic seeding by staph and strep
- Ascending infections: gram neg organisms, enterococcus (may present as cystitis)
Common infectious agents that may cause kidney infection/tubulo-interstitial inflammation?
Bacteria
- Staph, strep
- Gram (-) organisms, enterococcus
Viral: CMV, HIV, BK (polyoma), EBV, Hantavirus, herpes
Fungal: typ candida
Mycoplasma
Other: malaria, leptospira
What is seen here?
Pyelonephritis on CT scan
- Striated nephrogram- poorly perfused area
What can cause interstitial inflammation from a urinary reflux/obstruction standpoint?
- Clinical presentation
- Treatment
Vesico-urethral reflux nephropathy
- Caused by combo of VUR and infection, beginning in childhood
Clinically:
- Recurrent UTIs in childhood
- Slowly progressive loss of kidney function
Treatment
- Treat UTIs
- Correct severe VUR in children
- No benefit of surgery in adults
What is involved in acute drug induced interstitial nephritis and heavy metal toxicity as etiologies for interstitial inflammation? (Basic principles)
- The drugs causing interstitial inflammation are an unrelated group of agents that aren’t dose related and only occur in small number of exposed
- Overall, it’s a hypersensitivity reaction; recurs (severe) upon re-exposure
- May involve systemic manifestations
What drugs can cause interstitial inflammation?
Antibiotics
- Penicillins, methicillin, ampicillin
- Cephalosproins, floroquinolones (cipro)
- Rifampin
Sulfonamides
NSAIDs (analgesics)
Miscellaneous:
- Anticoags (Phenindione)
- Anticonvulsants (Phenytoin)
- Diuretics (Thiazides, Furosemide)
- Others: Cimetidine, Allopurinol, Cyclosporine, Omeprazole
Acute physical findings of tubule and interstitial disease?
- Fever, 50-75%
- Rash, 25-40%
- Eosinophilia, 40-60%
- Flank pain, 25-40%
- Hypertension, 10-20%
What is the association between Aristolochic acid and nephropathy?
Aristolochic acid nephropathy (AAN) aka Chinese herbal nephropathy
- Extensive paucicellular interstitial fibrosis and tubular atrophy typically found in end-stage CHN
Describe NSAID (analgesic) nephropathy:
- Clinical Presentation
- Onset
- Urinalysis
- Resolution
- Permanent damage (prevalence)
- Systemic manifestations
- Clinical Presentation: AKD +/- Nephrotic Syndrome
- Onset: 2 wks - 18 mo
- Urinalysis: microhematuria, pyuria
- Resolution: 1 mo - more than 1 yr
- Permanent damage (prevalence): perhaps > 15%
- Systemic manifestations: eosinophilia, fever, rash
Clinical Features of NSAID nephropathy?
- Gender
- Age
- Symptoms
- Gender: female > male (60-85%)
- Age > 30 yrs
- Personality disorder (Major 35% Minor 40% Introvert, dependent, anxiety, emotional disorder, neurotic, familial instability)
- Addictive syndrome (Smoking, alcohol, laxatives, sedatives, psychotropics)
- Cause of analgesic dependency (Headache 40-60%, mood 6-30%, musculoskeletal pain 20-30%)
Pathogenesis of NSAID nephropathy?
APC tabs or powders
- Aspirin blocks synthesis of prostaglandin (a vasodilator)
- Phenacetin (Acetaminophen)* lowers glutathione, which is needed to block intracellular oxidative stress
- Caffeine increases adenosine, a vasoconstrictor (works in headaches by decreasing CNS edema)
Results in papillary ischemia
*Can take Tylenol rather than Phenacitin/Acetaminophin
What is seen here?
NSAID nephropathy
- Dying papilla
- Dead tissue coming out in urine
How can creatinine levels be normal early on?
- Cortical nephron spared
- Decreased GFR, but early creatinine is normal ?
Treatment for NSAID Nephropathy?
- Discontinue analgesics
- Control blood pressure (ACEIs)
- Treat urinary infections
- Expand vascular volume
- Psychological support and guidance
- Monitor for uroepithilial neoplasms (5-10% of phenacetin users)
What heavy metals can cause nephrotoxicity?
Chronic TIN
- Lead
- Bismuth, Cadmium, Chromium, Copper, Iron, Mercury, Platinum, Silicon, Uranium
Acute TIN
- Bismuth
- Mercury
- Uranium
- Arsenic, Cadmium, Chromium, Copper, Gold, Iron, Lead, Silver
ATN and cortical necrosis can cause tubulo-interstitial inflammation. What does ATN involve?
Acute tubular necrosis involves multiple renal insults
- Preexisting renal damage
- Prerenal state: volume depletion, sepsis, heart failure
- Nephrotoxin exposure or kidney ischemia
What is the pathogenesis of ATN?
- Cell death due to toxin or ischemia
- With reperfusion, damaged cells undergo apoptosis
- Damaged cells sloughed off and new cells take their place
- Combination of vasoconstriction (pre renal state), ischemia, and toxin
- Vacuolization of tubules, loss of transport polarity
- Sloughing of cells, cast formation
- Recovery typically 1-3 weeks
- Clinical objective, keep patient alive till kidneys recover
What is seen here?
ATN in kidney biopsy
- Cells sloughing off in collecting tubule and forming cast
What nephrotoxins can cause acute tubular necrosis?
- IV iodinated radiographic contrast
- Heme pigments (myoglobin and hemoglobin)
- Certain antibiotics (aminoglycosides)
- Heavy metals (cis-platinum)
- Carbon tetrachloride and solvents
What can cause cortical necrosis?
Ischemia of cortex
- Microvascular thrombosis, glomerular and tubule damage
- Medulla may survive
- Damage is patchy, some renal function may remain
Obstetrical disorders, DIC, HUS (E. coli infxn)
Anuria or oliguria is common
What is seen here?
Cortical necrosis
What conditions can cause urinary crystals?
- Metabolic disease
- Medications
- Chemicals
- Other
Metabolic disease
- Cysteine
- Hyperuricemia
- Hypercalcemia
Medications
- Indinavir
- Foscarnet
- Sulfa drugs
Chemicals
- Antifreeze (oxalic acid crystals)
Triple phosphate crystals and staghorn calculi (chronic kidney infection with urea splitting agents)
What can cause Cysteinosis? Cysteinuria?
Cysteinosis- autosomal recessive
- Cysteine accumulates in cells
- Proximal nephron damaged, unable to reabsorb filtered glucose, bicarb, AAs (Fanconi syndrome)
Cystinuria- autosomal recessive
- Filtered cysteine not reabsorbed by proximal nephron
- High urinary levels precipitate in pH neutral or acid urine, causing cysteine kidney stones
What crystals are these?
What is Myeloma Cast Nephropathy?
- Plasma cell clone produces defective antibody parts, excessive kappa or lambda chains
- Direct proximal tubule toxicity, cast formation in collecting duct
- Associated bone lesions, proteinuria (kappa and lambda proteins not detected by urinary dip stick)
- Anemia
- Small anion gap (kappa and lambda are positively charged proteins)
What is seen here?
Myeloma Cast Nephropathy
- Due to toxicity of filtered light chain (kappa, lambda) proteins; Bence Jones
- Directly toxic to proximal tubular cells
- Precipitate int he distal and collecting tubules
What is papillary necrosis?
- Necrosis of papilla: long loops of Henle, vasa recta, collecting duct
- Flank pain, tissue in urine
- Sickle cell, analgesic abuse, pyelonephritis…
- Not usually oliguric or anuric (humans have multiple papilla)
What happens to the nephrone/tubule in renal papillary necrosis? GFR?
- Loss of justamedullary nephrons
- Cortical nephrons preserved
- Tubular dysfunction but GFR maintained until disease advanced
What is seen here?
Left: Normal
Right: Sickle cell renal disease
Summary:
- Tubule and interstitial diseases share a common inflammatory pathogenesis
- Interstitial renal disease results in characteristic tubule defects
- Multitudes of common substances can cause TIN-be suspicious and pay attention to prescribed and over-the-counter medications
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