A 52-year-old man, with a history of alcoholism, presents with loss of appetite, abdominal pain, and fever for the past 24 hours. He says he consumed 12 beers and a bottle of vodka 2 days ago. He reports a 19-year history of alcoholism. His blood pressure is 100/70 mm Hg, pulse is 100/min, respirations are 20/min, and oxygen saturation is 99% on room air. Laboratory findings are significant for the following:
Sodium 137 mEq/L
Potassium 3.4 mEq/L
Alanine aminotransferase (ALT) 230 U/L
Aspartate aminotransferase (AST) 470 U/L
Which of the following histopathologic findings would most likely be found on a liver biopsy of this patient?
Q2
A 25-year-old woman presents to her primary care physician complaining of several months of diarrhea. She has also had crampy abdominal pain. She has tried modifying her diet without improvement. She has many watery, non-bloody bowel movements per day. She also reports feeling fatigued. The patient has not recently traveled outside of the country. She has lost 10 pounds since her visit last year, and her BMI is now 20. On exam, she has skin tags and an anal fissure. Which of the following would most likely be seen on endoscopy and biopsy?
Q3
A 65-year-old man is brought to the emergency department because of a 1-day history of fever and disorientation. His wife reports that he had abdominal pain and diarrhea the previous day. He drinks 60 oz of alcohol weekly. His pulse is 110/min and blood pressure is 96/58 mm Hg. Examination shows jaundice, palmar erythema, spider nevi on his chest, dilated veins on the anterior abdominal wall, and 2+ edema of the lower extremities. The abdomen is soft and diffusely tender; there is shifting dullness to percussion. His albumin is 1.4 g/dL, bilirubin is 5 mg/dL, and prothrombin time is 31 seconds (INR = 3.3). Hepatitis serology is negative. A CT scan of the abdomen is shown. Which of the following processes is the most likely explanation for these findings?
Q4
An esophageal biopsy sample from a 47-year-old male with chronic heartburn reveals intestinal metaplasia. Which of the following abnormal cell types is likely present in this patient's esophagus?
Q5
A 21-year-old man comes to the physician because of a 6-month history of severe abdominal pain, bloating, and episodic diarrhea. He has also had a 5-kg (11-lb) weight loss during this time. Physical examination shows a mildly distended abdomen, hyperactive bowel sounds, and diffuse abdominal tenderness. A biopsy specimen of the colonic mucosa shows scattered areas of inflammation with fibrosis and noncaseating granulomas. Which of the following is most likely involved in the pathogenesis of this patient's condition?
Q6
A previously healthy 35-year-old woman comes to the physician for a 3-week history of alternating constipation and diarrhea with blood in her stool. She has not had any fevers or weight loss. Her father died of gastric cancer at 50 years of age. Physical examination shows blue-gray macules on the lips and palms of both hands. Colonoscopy shows multiple polyps throughout the small bowel and colon with one ulcerated polyp at the level of the sigmoid colon. Multiple biopsy specimens are collected. These polyps are most likely to be characterized as which of the following histological subtypes?
Q7
A 27-year-old woman presents to her primary care physician for evaluation of involuntary weight loss and recurrent abdominal pain. She noticed blood in her stool several times. The medical history is significant for the polycystic ovarian syndrome. The vital signs are as follows: temperature, 38.0°C (100.4°F); heart rate, 78/min; respiratory rate, 14/min; and blood pressure, 110/80 mm Hg. The family history is notable for paternal colon cancer. A colonoscopy is performed and is presented in the picture. What findings are expected?
Q8
A 51-year-old man presents to his primary care physician's office for a 6-week history of fatigue and diarrhea. He says that the diarrhea is frequent, small volume, and contains gross blood. Review of systems is significant for subjective fever and an unintentional 5-pound weight loss. He denies recent travel outside of the United States. His past medical history is significant for IV drug abuse, HIV infection with non-compliance, and osteoarthritis. His family history is significant for Crohn disease in his mother. His temperature is 100.7°F (38.2°C), pulse is 90/min, blood pressure is 129/72 mmHg, and respirations are 16/min. His abdominal exam shows mild right and left lower quadrant tenderness with no rebound or guarding. Laboratory results are significant for a CD4 count of 42/mm^3. Colonoscopy with tissue biopsy will most likely reveal which of the following?
Q9
A 65-year-old man comes to the physician because of abdominal pain and bloody, mucoid diarrhea for 3 days. He has been taking over-the-counter supplements for constipation over the past 6 months. He was diagnosed with type 2 diabetes mellitus 15 years ago. He has smoked one pack of cigarettes daily for 35 years. His current medications include metformin. His temperature is 38.4°C (101.1°F), pulse is 92/min, and blood pressure is 134/82 mm Hg. Examination of the abdomen shows no masses. Palpation of the left lower abdomen elicits tenderness. A CT scan of the abdomen is shown. Which of the following is the most likely underlying cause of the patient's condition?
Q10
A 24-year-old woman comes to the physician because of progressively worsening episodes of severe, crampy abdominal pain and nonbloody diarrhea for the past 3 years. Examination of the abdomen shows mild distension and generalized tenderness. There is a fistula draining stool in the perianal region. Immunohistochemistry shows dysfunction of the nucleotide oligomerization binding domain 2 (NOD2) protein. This dysfunction most likely causes overactivity of which of the following immunological proteins in this patient?
GI US Medical PG Practice Questions and MCQs
Question 1: A 52-year-old man, with a history of alcoholism, presents with loss of appetite, abdominal pain, and fever for the past 24 hours. He says he consumed 12 beers and a bottle of vodka 2 days ago. He reports a 19-year history of alcoholism. His blood pressure is 100/70 mm Hg, pulse is 100/min, respirations are 20/min, and oxygen saturation is 99% on room air. Laboratory findings are significant for the following:
Sodium 137 mEq/L
Potassium 3.4 mEq/L
Alanine aminotransferase (ALT) 230 U/L
Aspartate aminotransferase (AST) 470 U/L
Which of the following histopathologic findings would most likely be found on a liver biopsy of this patient?
A. Macronodular cirrhosis
B. T-lymphocyte infiltration
C. Periportal necrosis
D. Cytoplasmic inclusion bodies with keratin (Correct Answer)
E. Positive periodic acid-Schiff stain
Explanation: ***Cytoplasmic inclusion bodies with keratin***
- The patient's history of **heavy alcohol consumption**, acute presentation with fever, abdominal pain, and elevated **AST and ALT (AST:ALT ratio >2:1)**, are highly suggestive of **alcoholic hepatitis**.
- **Mallory bodies**, which are **cytoplasmic inclusions consisting of intermediate filaments (keratin)**, are a characteristic histopathologic finding in alcoholic hepatitis.
*Macronodular cirrhosis*
- While **alcoholic liver disease** can progress to cirrhosis, the acute presentation with fever and significant transaminase elevation points more towards **alcoholic hepatitis** rather than established macronodular cirrhosis as the primary acute event.
- **Macronodular cirrhosis** typically involves larger nodules of regenerating hepatocytes, but the *acute inflammatory changes* of alcoholic hepatitis are paramount in this presentation.
*T-lymphocyte infiltration*
- While some inflammatory cells are present in alcoholic hepatitis, **T-lymphocyte infiltration** is more characteristic of **chronic viral hepatitis** or **autoimmune hepatitis**.
- The liver injury in alcoholic hepatitis is primarily mediated by neutrophils and direct hepatotoxic effects of alcohol metabolites.
*Periportal necrosis*
- **Periportal necrosis** is more commonly seen in **viral hepatitis** or other forms of **acute hepatitis** where the inflammatory process is concentrated around the portal tracts.
- In alcoholic hepatitis, the damage is typically *centrilobular (zone 3)*, around the terminal hepatic venule, due to its hypoxic vulnerability and high cytochrome P450 activity.
*Positive periodic acid-Schiff stain*
- A **positive periodic acid-Schiff (PAS) stain** that is *diastase-resistant* is a characteristic finding in **alpha-1 antitrypsin deficiency**, a genetic disorder affecting the liver and lungs.
- This patient's clinical presentation and lab findings are inconsistent with alpha-1 antitrypsin deficiency and strongly point towards **alcoholic liver disease**.
Question 2: A 25-year-old woman presents to her primary care physician complaining of several months of diarrhea. She has also had crampy abdominal pain. She has tried modifying her diet without improvement. She has many watery, non-bloody bowel movements per day. She also reports feeling fatigued. The patient has not recently traveled outside of the country. She has lost 10 pounds since her visit last year, and her BMI is now 20. On exam, she has skin tags and an anal fissure. Which of the following would most likely be seen on endoscopy and biopsy?
A. Diffuse, non-focal ulcerations with granuloma
B. Diffuse, non-focal ulcerations without granuloma
C. Focal ulcerations with granuloma (Correct Answer)
D. Pseudopolyps and continuous mucosal involvement
E. Friable mucosa with pinpoint hemorrhages
Explanation: ***Focal ulcerations with granuloma***
- The patient's symptoms (diarrhea, crampy abdominal pain, fatigue, weight loss, skin tags, and anal fissure) are highly suggestive of **Crohn's disease**.
- **Crohn's disease** is characterized by **transmural inflammation** that often presents as **focal ulcerations** (skip lesions) and **non-caseating granulomas** on biopsy.
*Diffuse, non-focal ulcerations with granuloma*
- While granulomas are characteristic of Crohn's disease, the inflammation in Crohn's disease is typically **focal and discontinuous** (skip lesions), not diffuse.
- Diffuse inflammation with granulomas is less typical for inflammatory bowel disease and might prompt consideration for other granulomatous diseases not fitting this clinical picture.
*Diffuse, non-focal ulcerations without granuloma*
- **Diffuse ulcerations without granulomas** would be more suggestive of **ulcerative colitis**, but the presence of **skin tags** and **anal fissure** points away from this diagnosis and towards Crohn's disease.
- Ulcerative colitis is also characterized by **continuous inflammation** starting from the rectum, which is not described as focal.
*Pseudopolyps and continuous mucosal involvement*
- **Pseudopolyps** and **continuous mucosal involvement** are classic features of **ulcerative colitis**, not Crohn's disease.
- The patient's extraintestinal manifestations like **skin tags** and **anal fissure** are much more common in Crohn's disease.
*Friable mucosa with pinpoint hemorrhages*
- **Friable mucosa** and **pinpoint hemorrhages** are characteristic findings in **ulcerative colitis**, specifically indicating active inflammation and mucosal fragility.
- While these can be seen in inflammatory bowel disease, the full clinical picture with associated perianal disease is more specific for Crohn's disease.
Question 3: A 65-year-old man is brought to the emergency department because of a 1-day history of fever and disorientation. His wife reports that he had abdominal pain and diarrhea the previous day. He drinks 60 oz of alcohol weekly. His pulse is 110/min and blood pressure is 96/58 mm Hg. Examination shows jaundice, palmar erythema, spider nevi on his chest, dilated veins on the anterior abdominal wall, and 2+ edema of the lower extremities. The abdomen is soft and diffusely tender; there is shifting dullness to percussion. His albumin is 1.4 g/dL, bilirubin is 5 mg/dL, and prothrombin time is 31 seconds (INR = 3.3). Hepatitis serology is negative. A CT scan of the abdomen is shown. Which of the following processes is the most likely explanation for these findings?
A. Accumulation of iron in hepatocytes
B. Ground-glass hepatocytes with cytotoxic T cells
C. Fibrous bands surrounding regenerating hepatocytes (Correct Answer)
D. Misfolded protein aggregates in hepatocellular endoplasmic reticulum
E. Hepatocyte swelling with Councilman bodies and monocyte infiltration
Explanation: ***Fibrous bands surrounding regenerating hepatocytes***
- The patient presents with classic signs of **cirrhosis** (jaundice, palmar erythema, spider nevi, dilated abdominal veins, edema, ascites), acute decompensation (fever, disorientation, hypotension), and severe **hepatic dysfunction** (low albumin, high bilirubin, prolonged PT/INR). The history of heavy alcohol use supports this.
- **Cirrhosis** is histologically characterized by diffuse **fibrosis** and the formation of **regenerative nodules**, which are hepatocytes surrounded by fibrous bands, leading to disruption of normal liver architecture and function.
*Accumulation of iron in hepatocytes*
- This is characteristic of **hereditary hemochromatosis**, which leads to **iron overload** and organ damage, including cirrhosis.
- While hemochromatosis can cause cirrhosis, the patient's acute symptoms and specific liver histology (macronodular cirrhosis often seen in alcoholic liver disease) make alcoholic cirrhosis a more direct fit, and there is no mention of increased iron in labs.
*Ground-glass hepatocytes with cytotoxic T cells*
- **Ground-glass hepatocytes** are typically seen in **chronic hepatitis B infection**, representing an accumulation of HBsAg in the endoplasmic reticulum.
- While chronic hepatitis B can lead to cirrhosis, the negative hepatitis serology and direct evidence of alcohol abuse do not support this as the primary cause.
*Misfolded protein aggregates in hepatocellular endoplasmic reticulum*
- This description is characteristic of **alpha-1 antitrypsin deficiency**, where defective alpha-1 antitrypsin accumulates in hepatocytes.
- Although it can cause cirrhosis, the patient's symptoms are more consistent with alcoholic liver disease, and there is no mention of respiratory symptoms often associated with alpha-1 antitrypsin deficiency.
*Hepatocyte swelling with Councilman bodies and monocyte infiltration*
- **Hepatocyte swelling** and **Councilman bodies** (apoptotic hepatocytes) are features of **acute viral hepatitis** or other forms of acute liver injury. Monocyte infiltration can also occur.
- While acute liver injury can occur, the chronic stigmata of liver disease (spider nevi, palmar erythema, ascites) and the history of alcohol abuse point to a chronic process like cirrhosis rather than just acute inflammation.
Question 4: An esophageal biopsy sample from a 47-year-old male with chronic heartburn reveals intestinal metaplasia. Which of the following abnormal cell types is likely present in this patient's esophagus?
A. Polymorphonuclear leukocytes
B. Keratinized stratified squamous epithelium
C. Pseudostratified ciliated columnar epithelium
D. Goblet cells (Correct Answer)
E. Simple cuboidal epithelium
Explanation: ***Goblet cells***
- The presence of **goblet cells** is the histological hallmark of **intestinal metaplasia** in the esophagus, specifically **Barrett's esophagus**.
- **Chronic acid reflux** causes the normal stratified squamous epithelium to be replaced by columnar epithelium containing goblet cells, similar to the intestinal lining.
*Polymorphonuclear leukocytes*
- These cells, primarily **neutrophils**, are typically associated with **acute inflammation** or **infection**.
- While they can be present in inflammatory conditions of the esophagus, they are not the specific abnormal cell type indicative of intestinal metaplasia.
*Keratinized stratified squamous epithelium*
- This type of epithelium is characteristic of the **skin** and oral cavity, providing protection against abrasion and desiccation.
- The normal esophagus is lined by **non-keratinized stratified squamous epithelium**, and its keratinization in the esophagus would be an abnormal finding but not indicative of intestinal metaplasia.
*Pseudostratified ciliated columnar epithelium*
- This type of epithelium is typically found in the **trachea** and bronchi, specialized for mucus secretion and particulate removal.
- Its presence in the esophagus would be an abnormal finding, but it is not the specific cell type associated with intestinal metaplasia (Barrett's esophagus).
*Simple cuboidal epithelium*
- This type of epithelium is commonly found in glands, kidney tubules, and ducts, specialized for secretion and absorption.
- It is not typically found as a lining epithelium in the esophagus under normal or metaplastic conditions.
Question 5: A 21-year-old man comes to the physician because of a 6-month history of severe abdominal pain, bloating, and episodic diarrhea. He has also had a 5-kg (11-lb) weight loss during this time. Physical examination shows a mildly distended abdomen, hyperactive bowel sounds, and diffuse abdominal tenderness. A biopsy specimen of the colonic mucosa shows scattered areas of inflammation with fibrosis and noncaseating granulomas. Which of the following is most likely involved in the pathogenesis of this patient's condition?
A. Increased activity of type 1 T helper cells (Correct Answer)
B. Viral infection with intranuclear inclusions
C. Intestinal overgrowth of toxigenic bacteria
D. Accumulation of intracellular bacteria in macrophages
E. Ectopic secretion of serotonin
Explanation: ***Increased activity of type 1 T helper cells***
- The described clinical picture (abdominal pain, bloating, diarrhea, weight loss, and **noncaseating granulomas**) is classic for **Crohn's disease**.
- Crohn's disease is characterized by a **Th1-mediated immune response**, involving immune cells like **type 1 T helper cells** that produce pro-inflammatory cytokines such as **TNF-α** and **interferon-γ**.
*Viral infection with intranuclear inclusions*
- **Intranuclear inclusions** are characteristic features of certain viral infections, such as those caused by **cytomegalovirus (CMV)**, which can present with colitis.
- However, CMV colitis typically lacks **noncaseating granulomas** and the chronic, progressive nature associated with this patient's symptoms.
*Intestinal overgrowth of toxigenic bacteria*
- While **toxigenic bacteria** (e.g., *Clostridium difficile*) can cause severe colitis and diarrhea, their primary mechanism involves toxin production, leading to mucosal damage.
- This scenario would not typically present with **noncaseating granulomas** and chronic, diffuse inflammation characteristic of Crohn's disease.
*Accumulation of intracellular bacteria in macrophages*
- This mechanism is associated with conditions like **Mycobacterium avium complex (MAC) infection** or **Whipple's disease**, which involve foamy macrophages containing bacteria.
- However, these conditions do not typically present with the prominent **noncaseating granulomas** seen in Crohn's disease.
*Ectopic secretion of serotonin*
- **Ectopic serotonin secretion** is characteristic of **carcinoid syndrome**, often associated with neuroendocrine tumors.
- Symptoms typically include flushing, diarrhea, and bronchospasm, which are distinct from the abdominal pain, weight loss, and granulomatous inflammation described in this patient.
Question 6: A previously healthy 35-year-old woman comes to the physician for a 3-week history of alternating constipation and diarrhea with blood in her stool. She has not had any fevers or weight loss. Her father died of gastric cancer at 50 years of age. Physical examination shows blue-gray macules on the lips and palms of both hands. Colonoscopy shows multiple polyps throughout the small bowel and colon with one ulcerated polyp at the level of the sigmoid colon. Multiple biopsy specimens are collected. These polyps are most likely to be characterized as which of the following histological subtypes?
A. Hyperplastic
B. Serrated
C. Adenomatous
D. Hamartomatous (Correct Answer)
E. Inflammatory
Explanation: ***Hamartomatous***
- The combination of **mucocutaneous pigmentation** (blue-gray macules on lips and palms), a family history of **early-onset gastrointestinal cancer**, and widespread **gastrointestinal polyps** is highly suggestive of **Peutz-Jeghers syndrome**.
- Peutz-Jeghers polyps are histologically characterized as **hamartomas**, which are benign growths but carry a significant risk of malignant transformation over time.
*Hyperplastic*
- **Hyperplastic polyps** are generally small, sessile, and located in the rectosigmoid colon, with a very low malignant potential.
- They do not typically present with the extensive pancolonic distribution, mucocutaneous pigmentation, or genetic predisposition for cancer seen in this patient.
*Serrated*
- **Serrated polyps** include sessile serrated lesions and traditional serrated adenomas, which although having malignant potential, do not typically present with the distinct **mucocutaneous findings** characteristic of Peutz-Jeghers syndrome.
- They are also not associated with the same widespread distribution throughout the small bowel and colon as seen in this case.
*Adenomatous*
- **Adenomatous polyps** are the most common type of colorectal polyp and are well-known precursors to colorectal cancer.
- However, they do not typically present with **mucocutaneous pigmentation** on the lips and palms, nor do they often involve the small bowel as extensively as described, which points away from polyposis syndromes like Familial Adenomatous Polyposis (FAP) and towards Peutz-Jeghers syndrome in this specific clinical context.
*Inflammatory*
- **Inflammatory polyps** are usually associated with chronic inflammation, such as **inflammatory bowel disease (IBD)**, and are essentially pseudopolyps formed during cycles of ulceration and healing.
- While IBD can cause GI symptoms and blood in stool, the presence of **mucocutaneous pigmentation** and widespread polyps in the small bowel and colon makes inflammatory polyps an unlikely primary diagnosis in this patient.
Question 7: A 27-year-old woman presents to her primary care physician for evaluation of involuntary weight loss and recurrent abdominal pain. She noticed blood in her stool several times. The medical history is significant for the polycystic ovarian syndrome. The vital signs are as follows: temperature, 38.0°C (100.4°F); heart rate, 78/min; respiratory rate, 14/min; and blood pressure, 110/80 mm Hg. The family history is notable for paternal colon cancer. A colonoscopy is performed and is presented in the picture. What findings are expected?
A. Crypt abscess (Correct Answer)
B. Dermatitis herpetiformis
C. Blunting of villi and crypt hyperplasia
D. Non-caseating granulomas
E. Aphthous stomatitis
Explanation: ***Crypt abscess***
- The image provided shows **neutrophils infiltrating and filling the crypt lumina**, which are characteristic findings of crypt abscesses seen in **ulcerative colitis**.
- This pathology, combined with the patient's symptoms of **bloody diarrhea**, involuntary weight loss, and recurrent abdominal pain, points towards an inflammatory bowel disease, most consistent with ulcerative colitis.
*Dermatitis herpetiformis*
- This is a **skin manifestation of celiac disease**, presenting as intensely pruritic papules and vesicles, typically on extensor surfaces.
- It is not directly associated with inflammatory bowel disease, especially ulcerative colitis, and is not a histological finding in the colon.
*Blunting of villi and crypt hyperplasia*
- These are characteristic histological findings of **celiac disease** in the **small intestine**.
- The patient's symptoms and the histological image are from the colon, ruling out celiac disease as the primary diagnosis.
*Aphthous stomatitis*
- While **aphthous ulcers** are common extraintestinal manifestations in both Crohn's disease and ulcerative colitis, it is a clinical finding in the oral cavity, not a histological finding in the colon.
- The question asks for *other findings expected* in the context of the provided colonic histology.
*Non-caseating granulomas*
- **Non-caseating granulomas** are a hallmark histological feature of **Crohn's disease**, not ulcerative colitis.
- The image shown, with widespread crypt abscesses and diffuse inflammatory infiltrate, is more typical of ulcerative colitis rather than Crohn's disease.
Question 8: A 51-year-old man presents to his primary care physician's office for a 6-week history of fatigue and diarrhea. He says that the diarrhea is frequent, small volume, and contains gross blood. Review of systems is significant for subjective fever and an unintentional 5-pound weight loss. He denies recent travel outside of the United States. His past medical history is significant for IV drug abuse, HIV infection with non-compliance, and osteoarthritis. His family history is significant for Crohn disease in his mother. His temperature is 100.7°F (38.2°C), pulse is 90/min, blood pressure is 129/72 mmHg, and respirations are 16/min. His abdominal exam shows mild right and left lower quadrant tenderness with no rebound or guarding. Laboratory results are significant for a CD4 count of 42/mm^3. Colonoscopy with tissue biopsy will most likely reveal which of the following?
A. Flask-shaped amebic ulcers
B. Loosely adherent inflammatory exudates
C. Intranuclear and cytoplasmic inclusions (Correct Answer)
D. Lymphocytic mucosal infiltrates
E. Non-caseating granulomas
Explanation: ***Intranuclear and cytoplasmic inclusions***
- The patient's severe **immunocompromised state** (CD4 count 42/mm^3) and symptoms of bloody diarrhea and fever strongly suggest opportunistic infections, with **cytomegalovirus (CMV) colitis** being a leading diagnosis.
- **CMV** characteristically causes **intranuclear and cytoplasmic eosinophilic inclusion bodies** (owl's eye inclusions) in infected cells, best visualized on biopsy.
*Flask-shaped amebic ulcers*
- These are characteristic of **Entamoeba histolytica** infection (amebiasis), which typically presents with bloody diarrhea.
- While possible in an immunocompromised patient, the specific histopathological findings for CMV are more directly indicated given the profound immunosuppression.
*Loosely adherent inflammatory exudates*
- This description is typical of **pseudomembranous colitis**, most commonly caused by **Clostridioides difficile** infection.
- While _C. difficile_ can occur in immunocompromised patients, the clinical picture and expected biopsy findings in severe HIV are more suggestive of CMV.
*Lymphocytic mucosal infiltrates*
- This finding is common in various inflammatory conditions, including **lymphocytic colitis** and some forms of **inflammatory bowel disease (IBD)**.
- It is not specific enough to explain the severe symptoms in this profoundly immunocompromised patient, where an opportunistic pathogen like CMV is more likely.
*Non-caseating granulomas*
- **Non-caseating granulomas** are the hallmark histopathological feature of **Crohn disease**.
- While the patient's mother had Crohn disease, the acute onset of symptoms, severe immunosuppression, and the absence of classic chronic Crohn's features make Crohn disease less likely than an opportunistic infection like CMV.
Question 9: A 65-year-old man comes to the physician because of abdominal pain and bloody, mucoid diarrhea for 3 days. He has been taking over-the-counter supplements for constipation over the past 6 months. He was diagnosed with type 2 diabetes mellitus 15 years ago. He has smoked one pack of cigarettes daily for 35 years. His current medications include metformin. His temperature is 38.4°C (101.1°F), pulse is 92/min, and blood pressure is 134/82 mm Hg. Examination of the abdomen shows no masses. Palpation of the left lower abdomen elicits tenderness. A CT scan of the abdomen is shown. Which of the following is the most likely underlying cause of the patient's condition?
A. Focal weakness of the colonic muscularis layer (Correct Answer)
B. Twisting of the sigmoid colon around its mesentery
C. Transmural inflammation of the terminal ileum
D. Infiltrative growth in the descending colon
E. Decreased perfusion to mesenteric blood vessel
Explanation: **Focal weakness of the colonic muscularis layer**
- The patient's symptoms of **abdominal pain**, **bloody, mucoid diarrhea**, and **left lower abdominal tenderness** are classic for **diverticulitis**, which occurs when small pouches (diverticula) in the colon become inflamed or infected. Diverticula form due to **focal weakness in the colonic muscularis layer**, often at points where blood vessels penetrate the muscle wall.
- **Constipation** and a history of **smoking** are risk factors for diverticular disease, contributing to increased intraluminal pressure and the formation of diverticula.
*Twisting of the sigmoid colon around its mesentery*
- This describes a **sigmoid volvulus**, which presents with acute onset of **severe abdominal pain**, distension, and obstipation (complete absence of stool and gas).
- While a volvulus can cause bloody stools due to ischemia, the clinical presentation and likely CT findings (not provided, but inferred to show diverticula) are inconsistent with this condition, and the described symptoms point more towards inflammation.
*Transmural inflammation of the terminal ileum*
- This suggests **Crohn's disease**, which can cause abdominal pain and diarrhea. However, Crohn's disease typically affects the **terminal ileum** and has a more chronic course, often with weight loss, perianal disease, and extraintestinal manifestations.
- Bloody, mucoid diarrhea is less typical for Crohn's unless there is severe colonic involvement, and the acute onset and tenderness in the left lower quadrant point away from isolated terminal ileitis.
*Infiltrative growth in the descending colon*
- An **infiltrative growth** (e.g., colorectal cancer) can cause changes in bowel habits, abdominal pain, and bloody stools. However, it usually presents with more **chronic symptoms** and weight loss.
- The acute inflammatory picture presented (fever, tenderness, mucoid diarrhea) is less characteristic of an uncomplicated infiltrative growth without obstruction or perforation.
*Decreased perfusion to mesenteric blood vessel*
- This describes **ischemic colitis**, which causes acute abdominal pain, bloody diarrhea, and tenderness. While it's a possibility, especially in older patients with vascular risk factors (diabetes, smoking), the description of **mucoid diarrhea** and the strong association with a history of constipation and symptoms pointing to localized inflammation (tenderness in left lower abdomen suggesting sigmoid/descending colon involvement) make **diverticulitis** a more likely primary cause in this context unless imaging strongly suggests ischemia.
- Ischemic colitis often presents with more severe, diffuse abdominal pain often out of proportion to physical exam findings initially.
Question 10: A 24-year-old woman comes to the physician because of progressively worsening episodes of severe, crampy abdominal pain and nonbloody diarrhea for the past 3 years. Examination of the abdomen shows mild distension and generalized tenderness. There is a fistula draining stool in the perianal region. Immunohistochemistry shows dysfunction of the nucleotide oligomerization binding domain 2 (NOD2) protein. This dysfunction most likely causes overactivity of which of the following immunological proteins in this patient?
A. Interferon-γ
B. β-catenin
C. IL-1β
D. IL-10
E. NF-κB (Correct Answer)
Explanation: ***NF-κB***
- **NOD2** is a pattern recognition receptor that normally detects bacterial products and regulates inflammatory responses. In **Crohn's disease**, loss-of-function **NOD2 mutations** lead to impaired bacterial sensing and clearance.
- This defective NOD2 function results in **compensatory overactivation of NF-κB** through alternative inflammatory pathways (particularly TLR signaling), causing excessive **pro-inflammatory cytokine** production.
- This **NF-κB hyperactivation** is a key driver of chronic inflammation in **Crohn's disease**, contributing to symptoms like fistulas, strictures, and transmural inflammation.
*Interferon-γ*
- **Interferon-γ** is an important pro-inflammatory cytokine in Crohn's disease and is part of the Th1-mediated immune response.
- However, its production is downstream of **NF-κB** activation and other inflammatory cascades. **NOD2 dysfunction** does not directly cause **IFN-γ** overactivity through the primary molecular pathway.
*β-catenin*
- **β-catenin** is a key component of the **Wnt signaling pathway** involved in cell adhesion, proliferation, and differentiation.
- It is not directly affected by **NOD2 dysfunction**. Dysregulation of **β-catenin** is more commonly associated with colorectal adenomas and cancer, not the inflammatory mechanisms of Crohn's disease.
*IL-1β*
- **IL-1β** is a potent pro-inflammatory cytokine that is indeed elevated in **Crohn's disease**.
- However, **IL-1β** is produced **downstream** of **NF-κB** activation. The primary molecular consequence of **NOD2 dysfunction** is the overactivity of **NF-κB**, which then drives production of various cytokines including **IL-1β**.
*IL-10*
- **IL-10** is an **anti-inflammatory cytokine** essential for maintaining intestinal immune homeostasis and suppressing excessive inflammatory responses.
- In Crohn's disease, **IL-10** signaling is often **impaired or deficient** rather than overactive. The question asks about overactivity, making this the opposite of what occurs in the disease.