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
