A 45-year-old homeless man is brought to the emergency department. He was found unconscious at the park. The patient has a past medical history of IV drug abuse, hepatitis C, alcohol abuse, schizophrenia, and depression. He does not receive normal medical follow up or care. His temperature is 102°F (38.9°C), blood pressure is 97/68 mmHg, pulse is 120/min, respirations are 22/min, and oxygen saturation is 98% on room air. Physical exam demonstrates a diffusely distended abdomen that is dull to percussion with a notable fluid wave. The abdominal exam causes the patient to contract his extremities. Cardiac and pulmonary exam are within normal limits. The patient responds to painful stimuli and smells heavily of alcohol. Which of the following is the best next step in management?
Q82
A 55-year-old patient who immigrated from the Middle East to the United States 10 years ago presents to the emergency department because of excessive weakness, abdominal discomfort, and weight loss for the past 10 months. He has had type 2 diabetes mellitus for 10 years for which he takes metformin. He had an appendectomy 12 years ago in his home country, and his postoperative course was not complicated. He denies smoking and drinks alcohol socially. His blood pressure is 110/70 mm Hg, pulse is 75/min, and temperature is 37.1°C (98.7°F). On physical examination, the patient appears exhausted, and his sclerae are yellowish. A firm mass is palpated in the right upper abdominal quadrant. Abdominal ultrasonography shows liver surface nodularity, splenomegaly, and increased diameter of the portal vein. Which of the following is the most common complication of this patient condition?
Q83
A 60-year-old rock musician presents to the office because he has been feeling increasingly tired for the past 6 months. He has a history of intravenous drug use and alcohol abuse. He states that he feels quite tired, but he otherwise has no complaints. Physical examination is noncontributory. His laboratory values are normal other than moderately elevated liver enzymes. Which of the following additional tests should you order first?
Q84
A 36-year-old woman presents for a pre-employment health assessment. She has no complaints. Her last annual physical examination 8 months ago was normal. She has no significant past medical history. She is a nonsmoker and says she quit all alcohol consumption last year. A complete hepatic biochemistry panel is performed, which is significant for a serum alkaline phosphatase (ALP) level 5 times the upper limit of the normal range. Immunologic tests are positive for antimitochondrial antibodies. A liver biopsy is performed and reveals an inflammatory infiltrate surrounding the biliary ducts. Which of the following is the most likely diagnosis in this patient?
Q85
A 52-year-old man comes to the emergency department because of a 3-week history of abdominal distention, yellow coloring of the skin, and dark urine. He also reports malaise and progressive shortness of breath, associated with slight exertion, for several weeks. The patient is a chronic drinker, and he was diagnosed with cirrhosis 2 years ago. He was warned to stop drinking alcohol, but he continues to drink. He hasn't accepted any more testing and has refused to visit the doctor until now. His vital signs are heart rate 62/min, respiratory rate 26/min, temperature 37.4°C (99.3°F), and blood pressure 117/95 mm Hg. On physical examination, there is dyspnea and polypnea. Skin and sclera are jaundiced. The abdomen has visible collateral circulation and looks distended. There is diffuse abdominal pain upon palpation in the right hemiabdomen, and the liver is palpated 10 cm below the right costal border. The legs show significant edema. CT scan shows cirrhosis with portal hypertension and collateral circulation. During the fifth day of his hospital stay, the patient presents with oliguria and altered mental status. Laboratory studies show:
Day 1
Day 5
Hemoglobin
12.1 g/dL
11.2 g/dL
Hematocrit
33.3%
31.4%
Leukocyte count
7,000/mm3
6,880/mm3
Platelet count
220,000/mm3
134,000/mm3
Total bilirubin
20.4 mg/dL
28.0 mg/dL
Direct bilirubin
12.6 mg/dL
21.7 mg/dL
Creatinine
2.2 mg/dL
2.9 mg/dL
Albumin
3.4 g/dL
2.6 g/dL
PT
15 s
16.9 s
aPTT
19 s
35 s
Urinalysis
Negative for nitrite
Negative for leukocyte esterase
0–2 RBCs per high power field
0–1 WBC per high power field
No evidence of casts or proteinuria
What is the most likely cause of this patient's increased creatinine?
Q86
A 46-year-old woman presents to her primary care provider for itching. She reports that she has always had dry skin but that the itching has gotten significantly worse over the last few years. The patient also endorses fatigue and dull abdominal pain. Her past medical history includes Hashimoto’s thyroiditis, mitral valve prolapse, and osteoarthritis. She takes levothyroxine and ibuprofen for pain in her knees. The patient drinks 2-3 beers per week. She has a 10 pack-year smoking history but quit 15 years ago. She denies any family history of cancer. On physical exam, her sclera are anicteric. Her abdomen is soft and tender to palpation in the right upper quadrant. Her bowel sounds are normal and hepatomegaly is present. A right upper quadrant ultrasound shows no evidence of extrahepatic biliary dilation. Laboratory studies are performed which reveal the following:
Aspartate aminotransferase (AST): 76 U/L
Alanine aminotransferase (ALT): 57 U/L
Alkaline phosphatase: 574 U/L
Total bilirubin: 1.6 mg/dL
This patient is most likely to have which of the following additional findings?
Q87
A previously healthy 29-year-old African-American male comes to the physician with a 2-week history of progressive fatigue and shortness of breath on exertion. Last week he noticed that his eyes were gradually turning yellow and his urine was dark. He has a family history of type II diabetes. He denies changes in urinary frequency, dysuria, or nocturia. His temperature is 37°C (98.6° F), blood pressure is 120/80 mmHg, and heart rate is 80/min. Examination shows pale conjunctivae, splenomegaly, and jaundice. There is no lymphadenopathy. Laboratory studies show:
Hematocrit 19.5%
Hemoglobin 6.5 g/dL
WBC count 11,000/mm3
Platelet count 300,000/mm3
Reticulocyte count 8%
Serum
Total bilirubin 6 mg/dL
Direct bilirubin 1.0 mg/dL
Urea nitrogen 9 mg/dL
Creatinine 1 mg/dL
Lactate dehydrogenase 365 U/L
Peripheral blood smear shows gross polychromasia with nucleated red blood cells and spherocytes. Direct Coombs' test is positive. Which of the following is the most likely diagnosis?
Q88
A 45-year-old man comes to the physician because of fatigue and joint pain for 8 months. He has pain in both knees, both elbows, and diffuse muscle pain. He does not have dyspnea. He also had several episodes of a nonpruritic rash on his lower extremities. Eight years ago, the patient was diagnosed with hepatitis C. His temperature is 37.9°C (100.2°F), pulse is 90/min, and blood pressure is 140/90 mm Hg. Examination of the lower extremities shows raised purple papules that do not blanch when pressure is applied. Cardiopulmonary examination shows no abnormalities. Laboratory studies show:
Hemoglobin 13.9 g/dL
Leukocyte count 8,500/mm3
Platelets 160,000/mm3
Serum
Creatinine 1.1 mg/dL
ALT 123 U/L
AST 113 U/L
Further evaluation of this patient is most likely to show which of the following findings?
Q89
A 61-year-old man presents to the primary care clinic to establish care. He has not seen a physician for many years. He has no complaints or concerns but, on further questioning, does have some vague abdominal discomfort. He has no known past medical history and takes no medications. His social history is notable for injecting heroin throughout his late-teens and 20s, but he has been clean and sober for over a decade. At the clinic, the vital signs include: heart rate 90/min, respiratory rate 17/min, blood pressure 110/65 mm Hg, and temperature 37.0°C (98.6°F). The physical exam shows a slightly distended abdomen. The laboratory studies are notable for a platelet count of 77,000/uL and an international normalized ratio (INR) of 1.7. Which of the following is the next best step in the diagnosis of this patient?
Q90
A 65-year-old man comes to the physician because of progressive abdominal distension and swelling of his legs for 4 months. He has a history of ulcerative colitis. Physical examination shows jaundice. Abdominal examination shows shifting dullness and dilated veins in the periumbilical region. This patient's abdominal findings are most likely caused by increased blood flow in which of the following vessels?
Liver disease US Medical PG Practice Questions and MCQs
Question 81: A 45-year-old homeless man is brought to the emergency department. He was found unconscious at the park. The patient has a past medical history of IV drug abuse, hepatitis C, alcohol abuse, schizophrenia, and depression. He does not receive normal medical follow up or care. His temperature is 102°F (38.9°C), blood pressure is 97/68 mmHg, pulse is 120/min, respirations are 22/min, and oxygen saturation is 98% on room air. Physical exam demonstrates a diffusely distended abdomen that is dull to percussion with a notable fluid wave. The abdominal exam causes the patient to contract his extremities. Cardiac and pulmonary exam are within normal limits. The patient responds to painful stimuli and smells heavily of alcohol. Which of the following is the best next step in management?
A. Ceftriaxone
B. CT abdomen
C. Paracentesis (Correct Answer)
D. Cefotaxime
E. Ultrasound
Explanation: ***Paracentesis***
- The patient's **distended abdomen**, **dullness to percussion**, and **fluid wave** are classic signs of **ascites**. Given his history of **alcohol abuse** and **hepatitis C**, he is at high risk for cirrhosis-related ascites, which can become infected (spontaneous bacterial peritonitis, or **SBP**).
- A **paracentesis** is crucial for diagnosing SBP by analyzing the ascitic fluid for **cell count (especially PMNs)**, culture, and other parameters. It's the most appropriate first step in a patient with new-onset ascites or suspected SBP, especially if they are febrile.
*Ceftriaxone*
- While **antibiotics** are indicated for **spontaneous bacterial peritonitis (SBP)**, initiating empiric antibiotics like **ceftriaxone** before diagnostic paracentesis could mask the causative organism and make diagnosis difficult.
- Paracentesis is necessary to confirm SBP and guide specific antibiotic therapy, though empiric antibiotics should be started promptly after fluid collection if SBP is highly suspected.
*CT abdomen*
- A **CT scan** would provide detailed anatomical information but is not the most urgent or appropriate first step for diagnosing **SBP** or guiding immediate management in this setting.
- While it can confirm ascites, it cannot establish the diagnosis of infection or determine the fluid's cellular content, which is critical for treatment decisions.
*Cefotaxime*
- Similar to ceftriaxone, **cefotaxime** is an appropriate **antibiotic** for treating **spontaneous bacterial peritonitis (SBP)**.
- However, performing a **diagnostic paracentesis** to confirm SBP and obtain fluid for analysis is the priority before initiating empiric antibiotic therapy, just as with ceftriaxone.
*Ultrasound*
- An **ultrasound** can confirm the presence of **ascites** and rule out other causes of abdominal distension, and can also guide paracentesis.
- However, in a patient with suspected **spontaneous bacterial peritonitis (SBP)** and clear signs of ascites, performing the **diagnostic paracentesis** is the most direct and urgent next step to identify infection, making it more critical than just imaging.
Question 82: A 55-year-old patient who immigrated from the Middle East to the United States 10 years ago presents to the emergency department because of excessive weakness, abdominal discomfort, and weight loss for the past 10 months. He has had type 2 diabetes mellitus for 10 years for which he takes metformin. He had an appendectomy 12 years ago in his home country, and his postoperative course was not complicated. He denies smoking and drinks alcohol socially. His blood pressure is 110/70 mm Hg, pulse is 75/min, and temperature is 37.1°C (98.7°F). On physical examination, the patient appears exhausted, and his sclerae are yellowish. A firm mass is palpated in the right upper abdominal quadrant. Abdominal ultrasonography shows liver surface nodularity, splenomegaly, and increased diameter of the portal vein. Which of the following is the most common complication of this patient condition?
A. Hepatopulmonary syndrome
B. Ascites (Correct Answer)
C. Hepatic encephalopathy
D. Hepatorenal syndrome
E. Hepatic osteodystrophy
Explanation: ***Ascites***
- The patient presents with classic signs of **portal hypertension** (splenomegaly, increased portal vein diameter, liver surface nodularity suggesting cirrhosis), and **ascites** is the most common and often the earliest major complication.
- The presence of **abdominal discomfort** and an **RUQ mass** could be related to severe liver disease and its complications, including fluid accumulation or an underlying liver malignancy often associated with cirrhosis.
*Hepatopulmonary syndrome*
- This involves **intrapulmonary vascular dilatations** in the setting of liver disease leading to oxygenation defects, typically marked by platypnea and orthodeoxia, which are not described here.
- While a complication of **cirrhosis**, it is less common than ascites and typically presents with respiratory symptoms not highlighted in this case.
*Hepatic encephalopathy*
- Characterized by **neuropsychiatric symptoms** due to the accumulation of toxins (e.g., ammonia) that the liver cannot detoxify.
- The patient's presentation mainly focuses on physical weakness, abdominal issues, and jaundice, without mention of confusion, asterixis, or altered mental status.
*Hepatorenal syndrome*
- This is a form of **functional renal failure** that occurs in patients with advanced liver disease, presenting with rapidly progressive azotemia due to severe splanchnic vasodilation.
- It is a **later and more severe complication** of liver failure, and while possible, ascites is typically seen much earlier and more frequently.
*Hepatic osteodystrophy*
- This refers to a group of **metabolic bone disorders** (osteoporosis, osteomalacia) that can occur in chronic liver disease.
- While it can manifest as bone pain, it is not a direct or immediate complication of portal hypertension and would not explain the acute abdominal findings.
Question 83: A 60-year-old rock musician presents to the office because he has been feeling increasingly tired for the past 6 months. He has a history of intravenous drug use and alcohol abuse. He states that he feels quite tired, but he otherwise has no complaints. Physical examination is noncontributory. His laboratory values are normal other than moderately elevated liver enzymes. Which of the following additional tests should you order first?
A. Hepatitis C virus antibodies (Correct Answer)
B. Hepatitis B surface antigen
C. Hepatitis E virus-specific IgM antibodies
D. Hepatitis D virus-specific IgG antibody
E. Hepatitis A virus-specific IgM antibodies
Explanation: ***Hepatitis C virus antibodies***
- The patient's history of **intravenous drug use** and **chronic fatigue** with **elevated liver enzymes** strongly suggests chronic viral hepatitis, with hepatitis C being the most common blood-borne infection in persons with IVDU history.
- **Hepatitis C** is the **most prevalent chronic viral hepatitis** in the United States among persons with history of injection drug use, with transmission efficiency via needle sharing being very high.
- Hepatitis C often has a **long asymptomatic phase** (decades) before symptoms like fatigue and liver damage become apparent, making antibody testing the appropriate initial screen.
- While both HBV and HCV should ultimately be screened in this patient, **HCV prevalence is significantly higher** in the IVDU population, making it the priority initial test.
*Hepatitis B surface antigen*
- While **hepatitis B** can also be transmitted via intravenous drug use and cause chronic liver disease, **hepatitis C is more prevalent** in persons with IVDU history in the United States.
- **HBsAg** is used to detect active hepatitis B infection and should also be ordered, but given resource constraints and the clinical context, **anti-HCV is the higher-yield initial test**.
- Many IVDU patients have been vaccinated against HBV, further reducing its likelihood compared to HCV (for which no vaccine exists).
*Hepatitis E virus-specific IgM antibodies*
- **Hepatitis E** is typically transmitted via the **fecal-oral route** (contaminated water) and usually causes **acute, self-limiting hepatitis**, not chronic insidious fatigue and liver enzyme elevation in a Western patient.
- **IgM antibodies** would indicate an acute infection, which is less likely given the 6-month duration of symptoms.
- HEV rarely causes chronic infection except in immunocompromised patients.
*Hepatitis D virus-specific IgG antibody*
- **Hepatitis D** requires an existing **hepatitis B infection** to replicate (it's a satellite virus), meaning you would first need to confirm chronic hepatitis B before testing for HDV.
- While HDV can cause severe liver disease and is transmitted via blood exposure, it's not the initial test to pursue without evidence of HBV co-infection.
*Hepatitis A virus-specific IgM antibodies*
- **Hepatitis A** is transmitted via the **fecal-oral route** and causes an **acute, self-limiting infection** with complete resolution, rarely leading to chronic liver disease or persistent fatigue over 6 months.
- **IgM antibodies** are indicative of acute infection, which contradicts the chronic nature of the patient's symptoms.
- HAV does not cause chronic hepatitis.
Question 84: A 36-year-old woman presents for a pre-employment health assessment. She has no complaints. Her last annual physical examination 8 months ago was normal. She has no significant past medical history. She is a nonsmoker and says she quit all alcohol consumption last year. A complete hepatic biochemistry panel is performed, which is significant for a serum alkaline phosphatase (ALP) level 5 times the upper limit of the normal range. Immunologic tests are positive for antimitochondrial antibodies. A liver biopsy is performed and reveals an inflammatory infiltrate surrounding the biliary ducts. Which of the following is the most likely diagnosis in this patient?
A. Pancreatic cancer
B. Primary biliary cholangitis (Correct Answer)
C. Hepatic amyloidosis
D. Choledocolithiasis
E. Fascioliasis
Explanation: ***Primary biliary cholangitis***
- The combination of significantly elevated **alkaline phosphatase** (indicating cholestasis), positive **antimitochondrial antibodies (AMA)**, and an inflammatory infiltrate around the bile ducts on biopsy is highly diagnostic of primary biliary cholangitis (PBC).
- PBC is a **chronic autoimmune liver disease** predominantly affecting middle-aged women, characterized by progressive destruction of small intrahepatic bile ducts.
*Pancreatic cancer*
- Pancreatic cancer typically presents with symptoms like **jaundice**, weight loss, and abdominal pain, none of which are present in this asymptomatic patient.
- While it can cause cholestasis and elevated ALP, it would usually be associated with a **dilated common bile duct** on imaging and often obstructive symptoms.
*Hepatic amyloidosis*
- Hepatic amyloidosis can elevate ALP, but it would not typically be associated with **positive antimitochondrial antibodies**.
- Liver biopsy would show **amyloid deposits** rather than an inflammatory infiltrate surrounding biliary ducts.
*Choledocolithiasis*
- Choledocolithiasis (bile duct stones) would cause an **obstructive pattern** of elevated ALP, but it is often acutely symptomatic with **biliary colic** or cholangitis.
- It would not typically involve positive **antimitochondrial antibodies** or an inflammatory infiltrate characteristic of an autoimmune bile duct disease on biopsy.
*Fascioliasis*
- Fascioliasis is a **parasitic infection** that can cause eosinophilia and liver enzyme elevation, but it is associated with exposure to contaminated watercress or aquatic plants.
- It would not typically present with positive **antimitochondrial antibodies** and the specific inflammatory infiltrate seen in PBC.
Question 85: A 52-year-old man comes to the emergency department because of a 3-week history of abdominal distention, yellow coloring of the skin, and dark urine. He also reports malaise and progressive shortness of breath, associated with slight exertion, for several weeks. The patient is a chronic drinker, and he was diagnosed with cirrhosis 2 years ago. He was warned to stop drinking alcohol, but he continues to drink. He hasn't accepted any more testing and has refused to visit the doctor until now. His vital signs are heart rate 62/min, respiratory rate 26/min, temperature 37.4°C (99.3°F), and blood pressure 117/95 mm Hg. On physical examination, there is dyspnea and polypnea. Skin and sclera are jaundiced. The abdomen has visible collateral circulation and looks distended. There is diffuse abdominal pain upon palpation in the right hemiabdomen, and the liver is palpated 10 cm below the right costal border. The legs show significant edema. CT scan shows cirrhosis with portal hypertension and collateral circulation. During the fifth day of his hospital stay, the patient presents with oliguria and altered mental status. Laboratory studies show:
Day 1
Day 5
Hemoglobin
12.1 g/dL
11.2 g/dL
Hematocrit
33.3%
31.4%
Leukocyte count
7,000/mm3
6,880/mm3
Platelet count
220,000/mm3
134,000/mm3
Total bilirubin
20.4 mg/dL
28.0 mg/dL
Direct bilirubin
12.6 mg/dL
21.7 mg/dL
Creatinine
2.2 mg/dL
2.9 mg/dL
Albumin
3.4 g/dL
2.6 g/dL
PT
15 s
16.9 s
aPTT
19 s
35 s
Urinalysis
Negative for nitrite
Negative for leukocyte esterase
0–2 RBCs per high power field
0–1 WBC per high power field
No evidence of casts or proteinuria
What is the most likely cause of this patient's increased creatinine?
A. Hepatorenal syndrome (Correct Answer)
B. Chronic kidney disease
C. Pyelonephritis
D. Acute tubular necrosis
E. Glomerulonephritis
Explanation: ***Hepatorenal syndrome***
- This patient with **decompensated cirrhosis** and **oliguria** exhibits a rapid increase in **creatinine** (2.2 to 2.9 mg/dL over 4 days) without evidence of intrinsic kidney disease (negative urinalysis with no casts, minimal proteinuria). This points toward **Hepatorenal Syndrome (HRS)**, a severe complication of advanced liver disease.
- The **bland urinalysis** is the key diagnostic feature of HRS, distinguishing it from acute tubular necrosis. HRS results from severe vasoconstriction of renal arteries in the setting of splanchnic vasodilation from portal hypertension.
- The development of **altered mental status** along with worsening renal function further supports HRS, as it reflects progressive hepatic decompensation and hepatic encephalopathy.
*Chronic kidney disease*
- While patients with cirrhosis can develop CKD, the **rapid onset** of renal failure and oliguria over just 4 days, coupled with normal urinalysis, is less typical for primary chronic kidney disease exacerbation.
- CKD usually presents with more gradual changes in creatinine and may show signs of kidney damage (like proteinuria or casts) on urinalysis, which are absent here.
*Pyelonephritis*
- **Pyelonephritis**, a kidney infection, would typically present with fever, flank pain, and significant abnormalities on urinalysis such as **leukocyte esterase**, **nitrites**, and **white blood cell casts**, none of which are present.
- The absence of infectious markers in the urine makes pyelonephritis an unlikely cause of the acute renal deterioration.
*Acute tubular necrosis*
- **Acute tubular necrosis (ATN)**, often caused by ischemia or nephrotoxins, would typically show signs of tubular damage on urinalysis, such as **muddy brown casts** and renal tubular epithelial cells.
- The urinalysis in this case is bland, with no evidence of casts or significant cellular debris, ruling out ATN as the primary diagnosis.
*Glomerulonephritis*
- **Glomerulonephritis** would typically present with **hematuria**, **proteinuria**, and potentially **red blood cell casts** on urinalysis, indicating glomerular inflammation.
- The patient's urinalysis is benign, showing no red blood cell casts or significant proteinuria, making glomerulonephritis an unlikely diagnosis.
Question 86: A 46-year-old woman presents to her primary care provider for itching. She reports that she has always had dry skin but that the itching has gotten significantly worse over the last few years. The patient also endorses fatigue and dull abdominal pain. Her past medical history includes Hashimoto’s thyroiditis, mitral valve prolapse, and osteoarthritis. She takes levothyroxine and ibuprofen for pain in her knees. The patient drinks 2-3 beers per week. She has a 10 pack-year smoking history but quit 15 years ago. She denies any family history of cancer. On physical exam, her sclera are anicteric. Her abdomen is soft and tender to palpation in the right upper quadrant. Her bowel sounds are normal and hepatomegaly is present. A right upper quadrant ultrasound shows no evidence of extrahepatic biliary dilation. Laboratory studies are performed which reveal the following:
Aspartate aminotransferase (AST): 76 U/L
Alanine aminotransferase (ALT): 57 U/L
Alkaline phosphatase: 574 U/L
Total bilirubin: 1.6 mg/dL
This patient is most likely to have which of the following additional findings?
A. Anti-smooth muscle antibodies
B. Skin hyperpigmentation
C. Anti-neutrophil cytoplasmic antibodies
D. Personality changes
E. Hyperlipidemia (Correct Answer)
Explanation: ***Hyperlipidemia***
- This patient presents with symptoms and lab findings highly suggestive of **primary biliary cholangitis (PBC)**, including pruritus, fatigue, dull abdominal pain with RUQ tenderness, hepatomegaly, elevated AST/ALT, significantly elevated alkaline phosphatase, and mild hyperbilirubinemia.
- **Hyperlipidemia** is one of the most common metabolic complications of PBC, occurring in up to 75-85% of patients, often presenting early in the disease course due to impaired bile acid secretion and altered cholesterol metabolism.
- Total cholesterol can be markedly elevated (often >300 mg/dL), and this finding is more consistent and universal than other potential manifestations.
*Anti-smooth muscle antibodies*
- **Anti-smooth muscle antibodies (ASMA)** are primarily associated with **autoimmune hepatitis**, a condition characterized by significant elevations in transaminases (typically ALT > AST) rather than alkaline phosphatase predominance.
- PBC is characterized by **anti-mitochondrial antibodies (AMA)**, which are present in 90-95% of cases, not ASMA.
- The marked elevation in **alkaline phosphatase** and prominent pruritus point to a cholestatic process (PBC) rather than hepatocellular injury (autoimmune hepatitis).
*Skin hyperpigmentation*
- **Skin hyperpigmentation** does occur in PBC (in approximately 25-50% of patients) due to melanin deposition, particularly in sun-exposed areas and areas of prior scratching.
- However, **hyperlipidemia** is both more prevalent (affecting 75-85% vs 25-50%) and occurs earlier in the disease course, making it the most likely additional finding in this patient.
- Hyperpigmentation typically develops later as the disease progresses.
*Anti-neutrophil cytoplasmic antibodies*
- **Anti-neutrophil cytoplasmic antibodies (ANCA)** are primarily associated with **vasculitis**, such as granulomatosis with polyangiitis (Wegener's) or microscopic polyangiitis.
- This patient's clinical picture, with prominent pruritus and cholestatic liver enzyme pattern, does not suggest an underlying vasculitic process.
*Personality changes*
- **Personality changes** can be a feature of **hepatic encephalopathy**, which occurs in advanced liver failure due to the accumulation of neurotoxins like ammonia.
- While PBC can progress to cirrhosis and liver failure, the current presentation with only mild hyperbilirubinemia (1.6 mg/dL) and absence of neurological signs does not suggest significant encephalopathy at this stage.
- This would be expected only in advanced/decompensated disease.
Question 87: A previously healthy 29-year-old African-American male comes to the physician with a 2-week history of progressive fatigue and shortness of breath on exertion. Last week he noticed that his eyes were gradually turning yellow and his urine was dark. He has a family history of type II diabetes. He denies changes in urinary frequency, dysuria, or nocturia. His temperature is 37°C (98.6° F), blood pressure is 120/80 mmHg, and heart rate is 80/min. Examination shows pale conjunctivae, splenomegaly, and jaundice. There is no lymphadenopathy. Laboratory studies show:
Hematocrit 19.5%
Hemoglobin 6.5 g/dL
WBC count 11,000/mm3
Platelet count 300,000/mm3
Reticulocyte count 8%
Serum
Total bilirubin 6 mg/dL
Direct bilirubin 1.0 mg/dL
Urea nitrogen 9 mg/dL
Creatinine 1 mg/dL
Lactate dehydrogenase 365 U/L
Peripheral blood smear shows gross polychromasia with nucleated red blood cells and spherocytes. Direct Coombs' test is positive. Which of the following is the most likely diagnosis?
A. Paroxysmal nocturnal hemoglobinuria
B. Hereditary spherocytosis
C. Spur cell hemolytic anemia
D. Alpha thalassemia
E. Autoimmune hemolytic anemia (Correct Answer)
Explanation: ***Autoimmune hemolytic anemia***
- The triad of **anemia** (Hb 6.5 g/dL), **splenomegaly**, and **jaundice** (elevated total bilirubin with indirect predominance) suggests hemolysis.
- A **positive direct Coombs' test** confirms the presence of antibodies on the red blood cell surface, characteristic of autoimmune hemolytic anemia.
*Paroxysmal nocturnal hemoglobinuria*
- Characterized by **hemolytic anemia**, **thrombosis**, and impaired hematopoiesis, often with a **negative Coombs' test**.
- Symptoms are typically worse at night or in the morning due to increased acidosis, which is not described.
*Hereditary spherocytosis*
- While it presents with **spherocytes** and hemolytic anemia, it is due to intrinsic red blood cell membrane defects and has a **negative Coombs' test**.
- Often has a strong family history of anemia, jaundice, or gallstones, which is not mentioned in this patient's history.
*Spur cell hemolytic anemia*
- Associated with **severe liver disease** or **abetalipoproteinemia** and is characterized by acanthocytes (spur cells) on the peripheral smear.
- This patient has normal liver function tests (BUN, creatinine) and no history of severe liver disease.
*Alpha thalassemia*
- A genetic disorder causing impaired alpha-globin chain synthesis, leading to **microcytic, hypochromic anemia** and not typically spherocytes or a positive Coombs test.
- The severe forms (e.g., Hb Barts hydrops fetalis or Hb H disease) present earlier or have different characteristic red blood cell morphologies.
Question 88: A 45-year-old man comes to the physician because of fatigue and joint pain for 8 months. He has pain in both knees, both elbows, and diffuse muscle pain. He does not have dyspnea. He also had several episodes of a nonpruritic rash on his lower extremities. Eight years ago, the patient was diagnosed with hepatitis C. His temperature is 37.9°C (100.2°F), pulse is 90/min, and blood pressure is 140/90 mm Hg. Examination of the lower extremities shows raised purple papules that do not blanch when pressure is applied. Cardiopulmonary examination shows no abnormalities. Laboratory studies show:
Hemoglobin 13.9 g/dL
Leukocyte count 8,500/mm3
Platelets 160,000/mm3
Serum
Creatinine 1.1 mg/dL
ALT 123 U/L
AST 113 U/L
Further evaluation of this patient is most likely to show which of the following findings?
A. Elevated IgA in serum
B. Granulomatous inflammation of vessels
C. Hypocomplementemia (Correct Answer)
D. Elevated perinuclear anti-neutrophil cytoplasmic antibodies
E. Positive pathergy test
Explanation: ***Hypocomplementemia***
- The patient's history of **hepatitis C** infection, along with **fatigue, polyarthralgia, elevated liver enzymes, and palpable purpura**, is classic for **HCV-associated mixed cryoglobulinemia syndrome**.
- **Mixed cryoglobulinemia** (types II and III) involves immune complex deposition, which activates and consumes complement, leading to **low C3 and C4 levels** (hypocomplementemia).
- **Hypocomplementemia** is a hallmark laboratory finding and helps distinguish cryoglobulinemic vasculitis from other small vessel vasculitides.
*Elevated IgA in serum*
- Elevated IgA levels are characteristic of **IgA vasculitis (Henoch-Schönlein purpura)**, which typically affects children and presents with palpable purpura, abdominal pain, and glomerulonephritis.
- While IgA vasculitis can occur in adults, the strong association with **hepatitis C infection** and the typical adult presentation point toward cryoglobulinemia rather than IgA vasculitis.
*Granulomatous inflammation of vessels*
- **Granulomatous inflammation of vessels** is a hallmark of **Granulomatosis with Polyangiitis (GPA)** or **Eosinophilic Granulomatosis with Polyangiitis (EGPA)**.
- These conditions typically present with upper/lower respiratory tract involvement, renal disease, and **ANCA positivity**, not the pattern seen here.
*Elevated perinuclear anti-neutrophil cytoplasmic antibodies*
- **p-ANCA** (perinuclear anti-neutrophil cytoplasmic antibodies) are primarily associated with **microscopic polyangiitis** and **eosinophilic granulomatosis with polyangiitis (EGPA)**.
- The clinical picture of **HCV-associated mixed cryoglobulinemia** does not typically involve ANCA positivity; instead, **rheumatoid factor** and **cryoglobulins** would be the relevant serologic markers.
*Positive pathergy test*
- A **positive pathergy test** is characteristic of **Behçet's disease**, an inflammatory disorder causing recurrent oral and genital ulcers, skin lesions, and uveitis.
- This condition does not align with the patient's presentation of palpable purpura, polyarthralgia, and HCV-associated systemic symptoms.
Question 89: A 61-year-old man presents to the primary care clinic to establish care. He has not seen a physician for many years. He has no complaints or concerns but, on further questioning, does have some vague abdominal discomfort. He has no known past medical history and takes no medications. His social history is notable for injecting heroin throughout his late-teens and 20s, but he has been clean and sober for over a decade. At the clinic, the vital signs include: heart rate 90/min, respiratory rate 17/min, blood pressure 110/65 mm Hg, and temperature 37.0°C (98.6°F). The physical exam shows a slightly distended abdomen. The laboratory studies are notable for a platelet count of 77,000/uL and an international normalized ratio (INR) of 1.7. Which of the following is the next best step in the diagnosis of this patient?
A. Bone marrow biopsy
B. HIV ELISA
C. Hepatitis C antibody (Correct Answer)
D. Platelet aggregation assay
E. Anti-nuclear antibody test
Explanation: ***Hepatitis C antibody***
- The patient's history of **intravenous drug use** and the laboratory findings of **thrombocytopenia** and **elevated INR** strongly suggest chronic liver disease, most commonly caused by **hepatitis C virus (HCV) infection**.
- An **anti-HCV antibody test** is the appropriate initial screening test for HCV infection.
*Bone marrow biopsy*
- A bone marrow biopsy would be considered for unexplained **pancytopenia** or other specific hematological disorders, but the current clinical picture points to a more likely extra-medullary cause for the cytopenias related to liver disease.
- While it could identify issues with platelet production, it's not the first step when liver dysfunction is highly suspected.
*HIV ELISA*
- While a history of intravenous drug use is a risk factor for **HIV**, the patient's current symptoms and lab findings (thrombocytopenia, elevated INR, abdominal discomfort) are more characteristic of **chronic liver disease** rather than primary HIV complications.
- HIV testing would be reasonable as part of general health screening for this patient population, but it is not the *next best step* for the presenting concerns.
*Platelet aggregation assay*
- This assay evaluates platelet function, which is useful for diagnosing qualitative platelet disorders (e.g., Glanzmann's thrombasthenia, Bernard-Soulier syndrome).
- This patient has **thrombocytopenia** (low platelet *count*), not a functional disorder, and the elevated INR points away from primary platelet dysfunction.
*Anti-nuclear antibody test*
- An **ANA test** is used to screen for autoimmune diseases like **Systemic Lupus Erythematosus (SLE)**.
- While SLE can cause thrombocytopenia, the constellation of an elevated INR and a history of intravenous drug use makes liver disease a much more probable cause of the patient's symptoms.
Question 90: A 65-year-old man comes to the physician because of progressive abdominal distension and swelling of his legs for 4 months. He has a history of ulcerative colitis. Physical examination shows jaundice. Abdominal examination shows shifting dullness and dilated veins in the periumbilical region. This patient's abdominal findings are most likely caused by increased blood flow in which of the following vessels?
A. Hepatic vein
B. Superior rectal vein
C. Left gastric vein
D. Superior epigastric vein (Correct Answer)
E. Superior mesenteric vein
Explanation: ***Superior epigastric vein***
- This patient presents with signs of **portal hypertension**, including **jaundice**, **abdominal distension** (ascites), and **dilated periumbilical veins** (caput medusae). The **superior epigastric vein** is part of the **portosystemic anastomoses**, specifically connecting the **portal system** (via the paraumbilical veins) to the **systemic circulation** (via the inferior epigastric vein).
- Increased blood flow through these anastomoses, particularly the **paraumbilical veins** that drain into the epigastric veins, causes the characteristic **caput medusae** observed as dilated veins around the umbilicus, due to the shunting of portal blood away from the obstructed liver.
*Hepatic vein*
- Obstruction or increased flow in the **hepatic veins** (e.g., Budd-Chiari syndrome) would typically cause acute liver congestion and ascites but would not cause prominent **caput medusae** from shunting through periumbilical veins.
- While it contributes to hepatic outflow, it is not directly involved in the formation of **caput medusae** through portosystemic shunting at the umbilical level.
*Superior rectal vein*
- Increased blood flow in the **superior rectal vein** would lead to **hemorrhoids** as part of portosystemic anastomoses at the rectoanal junction (portal system via inferior mesenteric vein to systemic via middle and inferior rectal veins).
- This does not explain the **periumbilical dilated veins** or **caput medusae** seen in the patient.
*Left gastric vein*
- The **left gastric vein** is a significant site of portosystemic anastomosis, connecting to the **azygos system**, and increased flow causes **esophageal varices**.
- While a crucial site of shunting in portal hypertension, it does not explain the **dilated periumbilical veins** observed.
*Superior mesenteric vein*
- The **superior mesenteric vein** is a major tributary of the **portal vein**; increased flow within it would lead to increased portal pressure but is not itself a site of portosystemic anastomosis that would result in **caput medusae**.
- Pathologies directly affecting the superior mesenteric vein (e.g., thrombosis) would lead to mesenteric ischemia or bowel congestion, rather than the specific periumbilical venous dilation.