Exam 2: Acute Tubular Necrosis DSA Flashcards
1
Q
What is Acute Renal Failure (ARF)?
A
- an abrupt or rapid decline in the renal function
- A rise in serum BUN or creatinine concentration, with or without decrease in urine output, usually is evidence of ARF.
- ARF is often transient and completely reversible.
2
Q
What is Acute Tubular Necrosis (ATN)?
A
- ATN is the most common cause of ARF in the renal category
- ATN usually occurs after an acute ischemic or toxic event
3
Q
What causes Ischemic Acute Tubular Necrosis (ATN)?
A
- ATN is usually caused by an acute event, either ischemic or toxic.
-
Causes of Ischemic ATN:
- It may be considered part of the spectrum of prerenal azotemia and they have the same causes and risk factors
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Hypovolumic states
- hemorrhage, volume depletion from GI or renal losses, burns, fluid sequestration.
-
Low cardiac output states
- CHF and other diseases of the myocardium, valvulopathy, arrhythmia, pericardial diseases, tamponade.
-
Systemic vasodilation
- sepsis, anaphylaxis
- DIC
-
Renal vasoconstriction
- cyclosporine, norepinephrine, epinephrine, amphotericin B, etc
- Hyperviscosity syndrome
-
Impaired renal autoregulatory responses
- cyclooxygenase inhibitors
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Hypovolumic states
- It may be considered part of the spectrum of prerenal azotemia and they have the same causes and risk factors
4
Q
What causes Toxic Acute Tubular Necrosis (ATN)?
A
- ATN is usually caused by an acute event, either ischemic or toxic.
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Causes of Toxic ATN:
-
Exogenous Toxins
- Aminoglycosides
- Amphotericin B
- Radiocontrast media
- Cyclosporine and tacrolimus
- Sulfa drugs, acyclovir and indinavir
- Others: Cisplatin, methotrexate and foscarnet
-
Endogenous Toxins
- Myoglobinuria
- Hemoglobinuria
- Crystals
- Multiple myeloma
-
Exogenous Toxins
5
Q
Phases of Acute Tubular Necrosis (ATN)?
A
- ATN usually occurs after an acute ischemic** or **toxic event
- It has a well-defined sequence of events:
-
Initiation phase
- characterized by acute decrease in GFR to very low levels, with a sudden increase in serum Cr and BUN concentrations.
-
Maintenance phase
- is characterized by sustained severe reduction in GFR and the BUN and Cr continue to rise.
-
Recovery phase
- in which the tubular function is restored, is characterized by an increase in urine volume (if oliguria was present) and gradual decrease in Cr and BUN to their pre-injury level.
6
Q
Treatment of Acute Tubular Necrosis (ATN)?
A
- In general, an attempt is made to increase the urine output if oliguria is present, by using loop diuretics
- Only use diuretics if ECF volume and cardiac function are first carefully assessed and found adequate.
- The only true indication for diuretic use is volume overload.
- Furosemide and bumetanide are the commonly used diuretics.
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Dialysis treatment
- hemodialysis is still considered standard therapy in severe ARF
-
Indications for dialysis
- Clinical evidence of uremia
- intractable intravascular volume overload
- hyperkalemia
- severe acidosis resistant to conservative measures.
7
Q
Treatment of Complications
of Acute Tubular Necrosis (ATN)?
A
-
Volume overload:
- Salt and water restriction, diuretics. Dialysis for refractory cases.
-
Hyperkalemia:
- Restrict potassium intake, glucose and insulin, sodium bicarbonate, kayexalate, calcium gluconate, dialysis.
-
Metabolic acidosis:
- Sodium bicarb (only if HCO3 <15mmol/L or pH<7.2) or dialysis.
-
Hypocalcemia:
- Calcium carbonate, calcium gluconate.
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Infections:
- Antibiotics, assess the IV sites.
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Hyponatremia:
- Free water restriction.
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Hyperphosphatemia:
- Restrict phosphate intake, phosphate binding agents.
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Hypermagnesemia:
- Avoid Mg containing antacids.
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Anemia:
- Blood transfusion may be required.
8
Q
Phases of Acute Tubular Necrosis (ATN):
acute ischemic ATN Initiation phase
A
-
Ischemic ATN is often described as a continuum of prerenal azotemia (abnormally high levels of nitrogen-containing compounds in blood)
-
Response to fluid repletion can help distinguish between the two:
- return of renal function within 24-72 hours usually indicates prerenal disease, although short-lived ATN can recover within similar timeframe
-
Response to fluid repletion can help distinguish between the two:
-
1) Initiation phase
- Hypoperfusion initiates cell injury that often leads to cell death.
- It is most prominent in straight portion of the proximal tubules and thick ascending limb of loop of Henle.
- The reduction in the GFR occurs
- not only from reduced filtration due to hypoperfusion
- but also from casts and debris obstructing the lumen,
- causing back leak of filtrate through the damaged epithelium (ineffective filtration).
- In addition, ischemia leads to decreased production of vasodilators (i.e. nitric oxide, prostacyclin) by tubular epithelial cells
- leading to further vasoconstriction and hypoperfusion.
9
Q
Phases of Acute Tubular Necrosis (ATN):
acute ischemic ATN Maintenance phase
A
- Ischemic ATN is often described as a continuum of prerenal azotemia (abnormally high levels of nitrogen-containing compounds in blood)
-
2) Maintenance phase
- characterized by stabilization of GFR at a very low level
- it typically lasts 1-2 weeks.
- Uremic complications typically develop during this phase.
- In addition to the above previous mechanism of injury, tubulo-glomerular feedback also plays a role
- by causing constriction of afferent arterioles by the macula densa cells
- which detect an increased salt load in the distal tubules.
- by causing constriction of afferent arterioles by the macula densa cells
10
Q
Phases of Acute Tubular Necrosis (ATN):
acute ischemic ATN Recovery phase
A
- Ischemic ATN is often described as a continuum of prerenal azotemia (abnormally high levels of nitrogen-containing compounds in blood)
-
2) Recovery phase
- regeneration of tubular epithelial cells.
- An abnormal diuresis sometimes occurs
- causing salt and water loss and volume depletion.
- may in part be due to delayed recovery of tubular cell function in the setting of increased glomerular filtration.
- In addition, continued use of diuretics (often administered during initiation and maintenance phases) may also add to the problem.
- causing salt and water loss and volume depletion.
11
Q
Nephrotoxic ATN
A
- Most of the pathophysiological features of ischemic ATN are shared by the nephrotoxic forms and it has the same three phases.
-
Nephrotoxic injury to tubular cells occurs by multiple mechanisms including:
- direct toxicity
- intrarenal vasoconstriction
- and intratubular obstruction
12
Q
Ischemic or Toxic ATN?
A
Ischemic ATN
- A characteristic feature of ischemic ATN is the absence of widespread necrosis of tubular epithelial cells.
- Necrosis is more subtle and is reflected in individual necrotic cells within some proximal or distal tubules.
- These single cells shed into tubular lumen, with resulting focal denudation of the tubular basement membrane.
- Interstitial edema is common
13
Q
Ischemic or Toxic ATN?
A
Toxic ATN
- The morphology differs from Ischemic ATN in that Toxic ATN is characterized by more extensive necrosis of the tubular epithelium.
- In most cases, however, the necrosis is limited to certain segments that are most sensitive to the toxin.
- ATN caused by hemoglobin or myoglobin has added feature of numerous red-brown tubular casts, colored by heme pigments.
-
During the recovery phase of ATN, the tubular epithelium regenerates
- leading to the appearance of mitoses, increased size of cells and nuclei, and cell crowding.
- Survivors eventually display complete restoration of normal renal architecture.
14
Q
A
15
Q
Laboratory Findings Used to Differentiate
Prerenal Azotemia from ATN
A
- Loss of concentrating ability is an early and almost universal finding in ATN.
- None of the above criteria for the diagnosis of prerenal disease may be present in a patient with underlying renal disease. Hence, a cautious trial of fluids may be given.
