A 78-year-old man dies suddenly from complications of acute kidney failure. An autopsy is performed and microscopic evaluation of the kidneys shows pale, swollen cells in the proximal convoluted tubules. Microscopic evaluation of the liver shows similar findings. Which of the following is the most likely underlying mechanism of these findings?

Impaired Na+/K+-ATPase pump activity

Cytoplasmic triglyceride accumulation

An 84-year-old man is brought to the physician by the staff of a group home where he resides because of worsening confusion and decreased urinary output. His nurse reports that the patient has not been drinking much for the last 3 days. Examination shows a decreased skin turgor and dry oral mucosa. His pulse is 105/min and blood pressure is 100/65 mm Hg. His serum creatinine is 3.1 mg/dL and a urea nitrogen is 42 mg/dL. Urine studies show multiple brownish granular casts. Which of the following processes is most likely involved in the pathogenesis of this patient's condition?

Necrosis of tubular epithelial cells

Immune complex deposition in mesangium

Leukocytic infiltration of renal interstitium

Disruption of glomerular podocytes

A 39-year-old woman is brought to the emergency department in a semi-unconscious state by her neighbor who saw her lose consciousness. There was no apparent injury on the primary survey. She is not currently taking any medications. She has had loose stools for the past 3 days and a decreased frequency of urination. No further history could be obtained. The vital signs include: blood pressure 94/62 mm Hg, temperature 36.7°C (98.0°F), pulse 105/min, and respiratory rate 10/min. The skin appears dry. Routine basic metabolic panel, urine analysis, urine osmolality, and urine electrolytes are pending. Which of the following lab abnormalities would be expected in this patient?

Serum blood urea nitrogen/creatinine (BUN/Cr) > 20

Fractional excretion of sodium (FENa) > 2%

A 32-year-old man is brought to the Emergency Department after 3 consecutive days of diarrhea, fatigue and weakness. His stool has been soft and mucoid, with no blood stains. The patient just came back from a volunteer mission in Guatemala, where he remained asymptomatic. His personal medical history is unremarkable. Today his blood pressure is 98/60 mm Hg, pulse is 110/min, respiratory rate is 19/min, and his body temperature is 36.7°C (98.1°F). On physical exam, he has sunken eyes, dry mucosa, mild diffuse abdominal tenderness, and hyperactive bowel sounds. Initial laboratory tests are shown below: Serum creatinine (SCr) 1.8 mg/dL Blood urea nitrogen (BUN) 50 mg/dL Serum sodium 132 mEq/L Serum potassium 3.5 mEq/L Serum chloride 102 mEq/L Which of the following phenomena would you expect in this patient?

High urine osmolality, low FeNa+, low urine Na+

Low urine osmolality, high FeNa+, high urine Na+

High urine osmolality, high fractional excretion of sodium (FeNa+), high urine Na+

Low urine osmolality, high FeNa+, low urine Na+

Low urine osmolality, low FeNa+, high urine Na+

A 29-year-old woman comes to the physician because of a 2-day history of intermittent dark urine and mild flank pain. She has also had a cough, sore throat, and runny nose for the past 5 days. She has not had dysuria. She takes no medications. She has no known allergies. Her temperature is 37°C (98.6°F). Examination of the back shows no costovertebral angle tenderness. Laboratory studies show: Hemoglobin 10.4 g/dL Leukocyte count 8,000/mm3 Platelet count 200,000/mm3 Serum Na+ 135 mEq/L K+ 4.9 mEq/L Cl- 101 mEq/L HCO3- 22 mEq/L Urea nitrogen 18 mg/dL Creatinine 1.1 mg/dL Urine Color yellow Blood 3+ Protein 1+ Leukocyte esterase negative An ultrasound of the kidney and bladder shows no abnormalities. Which of the following is the most likely cause of this patient's symptoms?

Interstitial renal inflammation

Acute tubular necrosis for USMLE Step 2 CK: High-Yield Pathology Lessons

ATN Overview - Kidney's Downfall

Most common cause of acute kidney injury (AKI) in hospitalized patients, marked by tubular cell damage. It's often reversible.

Feature	Ischemic ATN	Nephrotoxic ATN
Pathophysiology	↓ Renal blood flow (hypoperfusion)	Direct tubular cell toxin exposure
Key Causes	Shock, sepsis, major surgery	Aminoglycosides, contrast, myoglobin
Tubular Segments	Proximal tubule & thick ascending limb	Primarily proximal tubule

⭐ Muddy brown casts in urine sediment are pathognomonic. The BUN:Cr ratio is often < 15:1 due to impaired urea reabsorption.

Pathophysiology - Cellular Chaos

Two major pathways converge on tubular epithelial cell injury:

Ischemic Injury: Most prominent in the proximal tubule (S3 segment) & thick ascending limb (TAL).
Nephrotoxic Injury: Primarily affects the proximal convoluted tubule (S1/S2) due to high reabsorptive function.

Pathophysiology of Acute Tubular Necrosis (ATN)

⭐ The S3 segment of the proximal tubule and the medullary thick ascending limb are classic sites for ischemic ATN due to high metabolic demand in a low-oxygen environment.

Morphology - Muddy Brown Mayhem

Gross: Enlarged, pale kidneys; swollen cortex, congested medulla.
Microscopy:
- Tubular Injury: Necrosis and sloughing of proximal tubular epithelial cells, with loss of brush border and tubular dilation. The basement membrane is typically spared.
- Casts: Pathognomonic muddy brown granular casts in distal tubules and collecting ducts.
- Interstitial edema.

Acute Tubular Necrosis with muddy brown casts

⭐ The proximal straight tubule and the thick ascending limb of Henle's loop are the most susceptible segments to ischemic injury.

Clinical Phases - The 3-Act Tragedy

A clinical course defined by three stages, tracking the progression from injury to resolution. The timeline and electrolyte shifts are key.

⭐ The BUN:Cr ratio is characteristically < 15:1 in ATN, as tubular dysfunction impairs urea reabsorption, distinguishing it from pre-renal azotemia where the ratio is > 20:1.

Diagnosis & Management - The Clinician's Clues

Urinalysis: Key to differentiate from prerenal azotemia.
- Microscopy: Muddy brown granular casts are pathognomonic.

Finding	Prerenal Azotemia	Acute Tubular Necrosis (ATN)
BUN:Cr Ratio	>20:1	<15:1
Urine Na+	<20 mEq/L	>40 mEq/L
FeNa	<1%	>2%
Urine Osmolality	>500 mOsm/kg	<350 mOsm/kg

- Address underlying cause (e.g., stop nephrotoxic drugs, restore perfusion).
- Manage fluid & electrolytes; loop diuretics for fluid overload.
- Indications for dialysis: 📌 **A**cidosis, **E**lectrolytes (hyperkalemia), **I**ngestions, **O**verload (refractory), **U**remia.

⭐ FeNa may be <1% in early sepsis- or contrast-induced ATN due to initial vasospasm.

High‑Yield Points - ⚡ Biggest Takeaways

The most common cause of acute kidney injury (AKI) in hospitalized patients.

Caused by ischemic or nephrotoxic injury to the renal tubules, particularly the proximal tubule and thick ascending limb.

Muddy brown granular casts in the urine are pathognomonic.

Key lab findings include a BUN:Cr ratio < 15:1 and a FENa > 2%.

Presents in three phases: initiation, maintenance (oliguric, hyperkalemia), and recovery (polyuric, hypokalemia).

Unlike cortical necrosis, ATN is potentially reversible.

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