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)
