ICL 1.9: Tubulointerstitial Disease Flashcards
a 25 year old male present to the ER after a car accident. He is hypotensive, diaphoretic and oliguric (low urine).
cause of oliguria?
acute tubular necrosis
this is the most important and most common cause of acute renal failure!!!
there’s ischemic damage to the kidney leading to ischemic damage to the nephron
what are the two major types of acute tubular necrosis?
- toxic
- ischemic
they both have the same clinical picture but just different morphologies –> they both lead to sudden damage to tubular epithelial cells
what are the phases of acute tubular necrosis?
- oliguria for 10-12 days
water + salt + potassium overload
hyperkalemia can lead to muscle weakness and bradycardia
urinalysis will show tubular cell casts (muddy brown casts*) and RBCs
there can also be metabolic acidosis
- polyuria after 10-12 days = increased volume of urine
decreased Na + K + Cl due to their loss in the urine
- recovery on the 17th day due to regeneration of the renal concentrating ability
what are the complications of acute tubular necrosis?
- cardiovascular = congestion, HTN and arrhythmias
2. CNS = lethargy, somnolence, twitching and seizures due to Na changes
which parts of the nephron are effected in acute tubular necrosis?
toxic is mostly in PCT while ischemic can effect PCT and loop of Henle
toxic is continuous while ischemic skips areas of the nephron
the distribution of the areas of necrosis is more segmental with ischemic injuries
toxic injuries result in more diffuse proximal tubular injury
what is the etiology of toxic acute tubular necrosis?
- heavy metals: mercury, lead, gold, arsenic*
- organic solvents: chloroform, carbon tetrachloride
- antibacterial: polymyxin, neomycin, sulfa
- mushrooms
- pesticides
- ethylene glycol (antifreeze)*
characteristics of the toxic damage is necrosis which is most prominent in the PCT!
what are the gross changes seen in toxic injuries result in acute tubular necrosis?
- pale, swollen kidney
2. edema
what are the microscopic changes seen in toxic injuries result in acute tubular necrosis?
necrosis is obvious and is associated with an intact basement membrane in toxic tubular necrosis
BM isn’t ruptured!
describe the acute tubular necrosis seen with ischemic injury?
- focal at multiple points with skip areas in between
- there is rupture of the basement membrane = tubulorhexis
- occlusion of the lumina by casts
- both proximal and distal tubules involved
what are the causes of ischemic tubular necrosis?
renal vasoconstriction and the factors behind it
they include dehydration which leads to hypovolemia and shock
what are the typical clinical situations associated with ischemic acute tubular necrosis?
- mismatched blood transfusion with massive hemolysis
- crush injury
- burns
- hemolysis
- gram negative septicemia* with DIC and pooling of blood in peripheral capillaries leading to poor perfusion of capillaries
a 15 year old girl presents with a skin rash and elevated creatinine after recovering from a sore throat.
UA: eosinophiluria
diagnosis?
pathogenesis?
acute interstitial nephritis due to hypersensitivity to drugs
she was fine but had a sore throat and then after she gets a skin rash and elevated creatinine which means kidney damage
she has eosinophils in the urine which occur when there’s a hypersensitivity reaction or parasites
she probably got antibiotics for sore throat and had an allergic reaction to it
a 65 year old lady with a 20 year history of Rheumatoid arthritis presents with elevated BUN and creatinine & mild hematuria.
diagnosis?
pathogenesis?
chronic interstitial nephritis from long term NSAID use!
associated with NSAID therapy – NSAIDs inhibit prostaglandins which leads to ischemia of the kidney and chronic inflammation = chronic interstitial nephritis
20 year history of RA is chronic
she’s 65 so she could have other issues….other issues that could lead to increase in BUN and creatinine could be HTN and CHF but she doesn’t have either of those so what is it…
did she get GOLD therapy for RA? she wouldn’t have hematuria and she’d be nephrotic with 4+ protein in the urine and edema which she doesn’t have either
people with RA take NSAIDs which lead to chronic interstitial nephritis!
what is acute interstitial nephritis?
inflammation of tubules and interstitium that causes acute renal failure without signs of nephrotic/nephritic syndromes
most often caused by hypersensitivity type I reaction to drugs/antibiotics but can also be caused by infections or systemic illnesses
associated with urinary tract infection treated with antibiotics
you’d see:
1. eosinophilia
- eosinophils in kidney and urine
- elevated IgE
- can sometimes see WBC casts without symptoms of cystitis = “sterile pyuria”
- fever, rash, malaise after exposure to a trigger
what is chronic interstitial nephritis?
mononuclear cells causing fibrosis and atrophy of tubules; often asymptomatic since it’s chronic and renal failure is identified incidentally
most often caused by chronic NSAID use or could also be phenacetin use; improves when you discontinue drug use
with aspirin you’d see decreased prostaglandins and ischemia
with phenacetin you’d see a direct toxic effect
both would result in papillary necrosis* and interstitial lymphocytes –> the ischemia causes papillary necrosis so then the kidney tries to expel the dead tissue which can cause pain!
70 year old male presents with low back pain and recurrent pneumonias for 4 months
PE: tenderness lumbar spine
CBC: Rouleaux, WBCs 2500, platelets 50,000
CMP: elevated Ca and total protein
diagnosis?
tests?
multiple myeloma
to confirm the diagnosis run serum protein electrophoresis where you’ll see an M spike and look at the bone marrow where you’ll see plasma cell proliferation
back pain = something is happening to the bones; probably lytic lesions of the bones –> this is causing high Ca+ in the serum
recurrent pneumonia = defense mechanisms are suppressed
rouleaux = myeloma!
low platelets and WBCs = leukopenia because bone marrow is being replaced by malignant cells which is why he has the recurrent infections
what are the renal changes in multiple myeloma?
- ostructive uropathy = viscous light chain casts obstruct the tubules
- destruction of tubular integrity when the viscous light chains stick to the tubules
- amyloidosis of the kidney = nephrotic syndrome, non-branching fibrils, apple-green bifringrance
- interstitial disease (malignant plasma cells can infiltrate interstitium)
- light chain glomerulonephritis = light chains expelled in the ruine and some of the light chains in the blood can elicit formation of immune complexes which go in the kidney and cause damage and appear as nodular lesions
- calcinosis
2 glomerular changes = amyloidosis, light chain nephropathy
3 tubular changes = Ca+ in lumen of tubules, obstruction from viscous light chains, damage to tubules
1 interstitial change = infiltration of the interstitium by the plasma cells
skin lesions with honey colored crust
impetigo associated with post-strep
painful lymphadenopathy with alcohol consumption
hodgkins lymphoma associated with minimal change
glomerular disease that is part of a systemic disease that can cause epistaxis
Wegners
HepC
- membranoprolierative (nephritic/nephrotic)
2. cryoglobulinemia (nephritic)
HepB
- membranous (nephrotic)
2. PAN (nephritic)
rapidly progressive
crescents
mesangialization
nephritic
specifically, membranoproliferative type I = split appearance in the capillaries
ribbon like deposits in lamina densa
membranoproliferative type II
C3 nephritic actor in serum
membranoproliferagie type II
poison ivy
membranous
GOLD therapy
membranous glomerulonephritis (nephrotic syndrome)
GI + skin + kidney in children
HS purpura
GI + skin + kidney in adults
PAN
schistocytes
- HUS
- TTP
- DIC
- malignant HTN
what conditions are NSAIDs associated with?
- acute interstitial nephritis
- chronic interstitial nephritis
- ischemic acute tubular necrosis
- membranous glomerulonephritis
- papillary necrosis
what are some of the most common causes of papillary necrosis?
- phenacetin (drug)
- DM
- acute pyelonephritis
- sickle cell*
patients will present with gross hematuria that’s painless and normal renal function
