Tubulointerstitial Diseases Flashcards
What is Acute kidney injury?
An abrupt impairment in renal function manifest by increased creatinine, increased BUN and oliguria
In extrememe cases of AKI what results?
Irreversible anuric renal failure with increasesed creatinine and potassium as well as acidosis. Fatality in a matter of days or sooner if hyperkalemia triggers cardiac arrhythmia
What is the most common cause of AKI?
Ischemia.
What is the most common histopathologic counterpart to AKI?
Acute Tubular necrosis
What is the most common cause of acute tubular necrosis?
Systemic disease affecting the kidney or multi-organ disease affecting the kidney.
What is the most common cause of the ischemia resulting in Acute Tubular Necrosis?
Shock….especially septic shock.
What is the second most common cause of ATN?
Nephrotoxins.
What is the most common nephrotoxin which causes ATN?
Radiologic contrast dye.
What anatomical structure does renal ischemia usually spare?
The Glomeruli!
What is the name of the type of Ischemia that affects the Glomeruli?
Cortical Necrosis.
What is the difference between tubular necrosis and Glomerular necrosis?
Tubular necrosis is reversible.
How is Tubular necrosis reversible?
The epithelial tubular cells die but the Basement membrane is still intact and there are stem cells there that can regenerate and replace the lost epithelial cells.
What is the standard time for tubular regeneration?
1-3 weeks but may take up to 6 weeks.
What feature of the renal medulla makes it even more susceptible to ischemia?
The epithelial cells are incapable of anaerobic metabolism
What portion of the medulla is most prone to ischemia?
The outer medulla is a major target of hypoxic injury because of regional hypoxia and metabolic oxygen demand of the portions of the tubules there
What are the portions of the tubule in the Outer medulla?
- Straight portion of the Proximal tubule
2. Thick ascending limbs of the loop of Henle
What molecules would be found in increased amounts arterioles in post ischemic kidney?
- Endothelin 1
- Angiotensin II
- Thromboxane A2
- PGH2
- Leukotriene C4
- Leukotriene D4
- Adenosine
What would post ischemia arterioles of the outter medulla show?
Reduced vasodilation in response to acetylcholine, bradykinin and NO
What are the cytokines which play a role during ischemia?
- I-1-beta
- IL-6
- IL-12
- IL-15
- IL-18
- IL-32
- TNF-alpha
- endothelin
How is the tubular epithelium actively involved in the inflammatory response during ischemia?
Injured tubular epithelial cells produce proinflammator chemotactic cytokines such as:
- TNF-alpha
- IL-1-beta
- TGF beta
- IL-6
- IL-8
- MCP-1
- RANTES
- ENA-78 (endothelial neutrophil activating protein 78)
What happens to kidneys with ATN?
- Usually become enlarged up to 30%
- Pale cortex
- Congested Medulla (especially in the region near the corticomedullary junction.
What is one of the early findings in ATN on light microscopy?
Loss of brush border and Bleb formation in its place.
What are some other early signs of ATN?
- Diffuse tubular epithelial cell edema
2. Vacuolization of the cytoplasm
What else has some of the same signs as early ATN?
- Calcineurin toxicity
2. Osmotic Diuresis (hetastarch, mannitol)
What morphological changes occur in the epithelial cells?
Normally are cuboidal become Flat
What form of necrosis occurs in the renal tubular epithelial cells in ATN?
Coagulative necrosis
What forms in the tubules during ATN?
Casts from cells that have sloughed off and mixed with proteinacious debris.
In rhabdomyolysis (necrosis of skeletal muscle) what forms the casts?
Rhabdomyolysis releases myoglobin which precipitates in renal tubules creating myoglbin casts which contribute to ATN
How are myoglobin casts different from the ones generated from the casts generated in ATN from ischemia?
Myoglobin casts are denser, more acellular and more intensly and darkly eosinophilic. (Can also use stains to show presence of myoglobin in tissue)
What are the signs of acute tubular necrosis from Ethylene Glycol consumption?
Acute tubular necrosis with prominent cytoplasmic vacuoles and formation of Oxalate crystals in the tubular lumen.
What is the morphology of the Oxalate crystals from Ethylene Glycol induced ATN?
These are translucent, rounded and fragment into wedge shapes with tissue sectioning.
What is the morphology of cells in the recovery phase of ATN?
Initial replacement cells are very flat like squamous cells and mitoses can be sometimes found.
What are the symptoms of ATN?
- Anorexia progressing through nausea to vomiting
- Pruritis
- Confusion
- Lethargy
- G.I hemorrhage
- Epistaxis
- Dysfunctional platelets
What do patients with ATN frequently suffer from hypotension?
This is because patients suffering with ATN usually are suffering from shock.
What is the effect of ATN on urine output.
Low urine output is a manifestation of ATN.
What are 2 staple features of ATN?
- Hyperkalemia
2. Metabolic acidosis
What lab test can help make a specific diagnosis?
Urinanalysis
What are the type of casts present in ATN?
Granular Muddy brown casts
What are the values of urine sodium in ATN?
High
What is the treatment for ATN?
Dialysis if the patient can tolerate it
What is a key determinant for whether a patient needs dialysis in ATN?
Potassium
What is the consequence of hyperkalemia?
Cardiac Arrhythmia
What is a major concern during the recovery phase of ATN?
Hypokalemia