Pathophysiology

Liver

Case Study

Patient Profile

Name: Mr. Marco Rubino

Age: 62 years old

Gender: male

History of Present Illness

M.R. is a 62-year-old man who reports worsening fatigue that interferes with his daily activities and household tasks, persistent nausea with intermittent vomiting that began approximately 10 days ago and has not improved, lack of appetite leading to decreased intake, and unintentional weight loss of three pounds in the last week. He also noticed his urine has been brownish for about a week despite drinking more liquids, reports mild itching on his arms and trunk from dry skin. He denies any fevers, night sweats, or mental status changes.

Past Medical History

Hypertension, type 2 diabetes (T2DM), hyperlipidemia

Current Medications

  • Amlodipine 5 mg daily
  • Metoprolol 50 mg BID
  • Metformin 500 mg BID
  • Atorvastatin 20 mg nightly
  • Acetaminophen for chronic back pain, takes two tablets now up to four times a day, occasionally at night, recently switched to extra strength because pain has been worse.

Social History

  • Retired engineer
  • Former smoker (quit 10 years ago)
  • Occasional alcohol consumption (2 drinks/week)
  • No illicit drug use

Family History

Father had T2DM, Mother had hypertension, two sisters ages 56 and 60, both with hypertension and obesity.

Physical Assessment

  • General Appearance: Alert, oriented, appears fatigued.
  • Vital Signs: Blood pressure 140/85 mm Hg, heart rate 82 bpm, respiratory rate 16/min, temperature 98.6°F.
  • HEENT: Mild scleral icterus observed.
  • Abdomen: Mild tenderness in the right upper quadrant, liver edge palpable 2 cm below the costal margin, no evidence of ascites upon percussion, bowel sounds positive in all quadrants.
  • Skin: Appears mildly jaundiced, with visible yellowing in palms, soles, and face, no spider angiomas or palmar erythema noted.
  • Neurological: No focal deficits, no signs of confusion or cognitive impairment.
  • Extremities: No asterixis with extension of hands, no peripheral edema.

Diagnostic Assessment

Hepatitis Panel: Negative

Liver Function Tests:

  • Alanine transaminase (ALT): 220 U/L (elevated)
  • Aspartate transaminase (AST): 190 U/L (elevated)
  • Alkaline phosphatase (ALP): 140 U/L (slightly elevated)
  • Gamma-glutamyltransferase (GGT): 80 U/L (elevated)
  • Total Bilirubin: 2.5 mg/dL (elevated)
  • Direct Bilirubin: 1.4 mg/dL (elevated)

Complete Blood Count: WNL

  • Hemoglobin (Hb): 16
  • Hematocrit (Hct): 48%
  • Red Blood Cell (RBC) Count: 5.12
  • White Blood Cell (WBC) Count: 7,300 cells per microliter.
  • Platelet Count: 384,000 platelets per microliter.
  • Mean Corpuscular Volume (MCV): 90 femtoliters.
  • Mean Corpuscular Hemoglobin (MCH): 29 picograms per cell.
  • Mean Corpuscular Hemoglobin Concentration (MCHC): 34/dL.

Abdominal Ultrasound: Mild hepatomegaly, no gallstones.

Diagnosis

Drug-induced liver injury (DILI).

Pathophysiology

DILI occurs when medications or other substances cause liver damage, either through direct hepatotoxic effects or metabolites produced during drug metabolism. The injury can be dose-dependent and predictable (as with acetaminophen) or idiosyncratic and unpredictable (as with many other drugs).

Mr. Rubino’s comorbidities—T2DM, hypertension, and hyperlipidemia—may increase his susceptibility to DILI. Diabetes and dyslipidemia are associated with non-alcoholic fatty liver disease (NAFLD), which reduces hepatic reserve and increases vulnerability to drug-induced injury. Polypharmacy, common in patients with multiple chronic conditions, further increases the risk of DILI due to potential drug-drug interactions and cumulative hepatic burden.

Excessive acetaminophen use is a common cause of liver injury, particularly in overdose situations or when used chronically at high doses. The liver metabolizes acetaminophen into a toxic metabolite, N-acetyl p-benzoquinone imine (NAPQI), which is usually detoxified by glutathione. However, in overdose situations, glutathione reserves are depleted, leading to NAPQI accumulation, oxidative stress, and liver cell necrosis. DILI is a serious medical condition that can lead to acute liver failure if not promptly treated. Acetaminophen overdose can cause rapid and severe liver damage. Early intervention with treatments like N-acetylcysteine (NAC), which replenishes glutathione stores and helps prevent further liver damage and necrosis, is critical.

Activity: Physical Signs and Symptoms of DILI from Acetaminophen

Fill in the blanks with the correct term: Right Upper Quadrant (RUQ), Left Upper Quadrant (LUQ), jaundice, light, dark, encephalopathy, bleeding, clotting, meningitis.

Early Symptoms (within 24 hours): Nausea and Vomiting, ____________________ abdominal pain, loss of appetite.

Progressive Symptoms (24 to 72 hours): Increased abdominal pain, ____________________ due to increased bilirubin levels, ____________________ urine, and pale stools due to altered bilirubin processing, fatigue, and malaise.

Advanced Symptoms (72 to 96 hours): Confusion and cognitive changes due to hepatic ____________________ as toxins build up in the blood, severe jaundice and dark urine, bleeding due to impaired synthesis of clotting factors, hypoglycemia as glucose regulation is compromised, and liver failure.

Review Questions

Click the arrow to expand the section and view the correct answers.

  1. What is the most likely cause of Mr. Rubino’s liver injury?
    1. Alcohol consumption
    2. Acetaminophen use
    3. Metformin
    4. Lisinopril
Answer:

B) Acetaminophen use

Feedback: Acetaminophen is a common cause of DILI, especially with chronic use or overdose.

  1. Which laboratory finding is most indicative of hepatocellular injury?
    1. Elevated ALP
    2. Elevated ALT
    3. Elevated GGT
    4. Elevated direct bilirubin
Answer:

B) Elevated ALT

Feedback: ALT is more specific to liver injury than other enzymes, indicating hepatocellular damage.

  1. What is the primary role of the liver in drug metabolism?
    1. Excrete drugs in their original form.
    2. Convert drugs into active compounds.
    3. Make drugs more water soluble for excretion.
    4. Bind drugs to plasma proteins.
Answer:

C) Make drugs more water soluble for excretion.

Feedback: The liver metabolizes drugs to make them more water soluble for easier excretion by the kidneys.

  1. What enzyme level is most specific to alcohol-related liver damage?
    1. ALT
    2. GGT
    3. AST
    4. ALP
Answer:

B) GGT

Feedback: GGT is often elevated in alcohol-related liver disease, although ALT is more specific to liver cells.

  1. Which diagnostic test is best for assessing the liver’s synthetic function?
    1. ALT level
    2. Total bilirubin
    3. Albumin level
    4. Abdominal ultrasound
Answer:

C) Albumin level

Feedback: Low albumin indicates decreased protein synthesis capacity in the liver.

  1. What is the normal role of the cytochrome P450 enzyme system?
    1. Increase drug toxicity.
    2. Decrease drug solubility.
    3. Facilitate drug biotransformation.
    4. Bind drugs to albumin.
Answer:

C) Facilitate drug biotransformation.

Feedback: Cytochrome P450 enzymes are critical for the metabolism and detoxification of many drugs.

  1. Which of the following increases the risk of DILI in the elderly?
    1. Selective renal excretion.
    2. Increased liver mass.
    3. Polypharmacy.
    4. Enhanced immune response.
Answer:

C) Polypharmacy.

Feedback: The use of multiple medications increases the risk of interactions and liver injury in older adults.

  1. What initial management step is crucial in suspected acetaminophen overdose?
    1. Administer activated charcoal.
    2. Provide intravenous fluids.
    3. Initiate NAC therapy.
    4. Perform a liver biopsy.
Answer:

C) Initiate NAC therapy.

Feedback: NAC is an antidote that replenishes glutathione and helps prevent liver damage.

  1. What drug on Mr. Rubino’s medication list is the most likely to contribute to drug-induced liver injury in conjunction with the acetaminophen?
    1. Atorvastatin
    2. Metoprolol
    3. Amlodipine
    4. Metformin
Answer:

A) Atorvastatin

Feedback: Atorvastatin is a statin used to lower cholesterol. Statins are metabolized in the liver and can produce a mild, asymptomatic elevation of liver enzymes, especially when administered with CYP3A4 inhibitors.

  1. Given Mr. Rubino’s social history (2 drinks/week), what is the most likely role of his alcohol use in the development of his liver injury?
    1. His occasional alcohol use is unlikely to be the primary cause, but could contribute to his risk when combined with acetaminophen.
    2. His alcohol use is the most likely cause of his liver injury.
    3. His alcohol use completely protects him from DILI.
    4. Alcohol consumption is irrelevant when assessing DILI risk.
Answer:

A) His occasional alcohol use is unlikely to be the primary cause, but could contribute to his risk when combined with acetaminophen.

Feedback: While Mr. Rubino’s alcohol consumption is occasional and not excessive, but even moderate use can increase the risk of DILI when combined with chronic or high-dose acetaminophen. Alcohol induces hepatic enzymes and may deplete glutathione, both of which make acetaminophen toxicity more likely. However, acetaminophen remains the primary culprit in this case.

References

Heavey, E. (2024). Lecture on the pathophysiology of the liver. [Transcript].

Larson, A. (2025). Up to Date: Drug induced liver injury. Available at: https://www.uptodate.com/contents/drug-induced-liver-injury

National Institute of Diabetes and Digestive and Kidney Diseases. (2023). LiverTox: Clinical and research information on drug induced liver injury. https://www.ncbi.nlm.nih.gov/books/NBK547852/

OpenAI. (2023). GPT 4 [Large language model]. https://www.openai.com/research/gpt

Tkacs, N. (Ed.). (2020). Advanced physiology and pathophysiology: Essentials for clinical practice. Springer Publishing Company.

You.com. (2024). https://www.you.com

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Be Prepared for Your Nurse Practitioner Clinical Readiness Exam Copyright © 2026 by Elizabeth Heavey, Renee Biedlingmaier, Colleen Burgoyne and Carnel C. Jackson is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, except where otherwise noted.

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