9.4 Gastrointestinal, Hepatobiliary & Endocrine Pathology
Key Takeaways
Crohn disease is transmural with skip lesions and noncaseating granulomas, while ulcerative colitis is continuous mucosal inflammation starting in the rectum; both can cause erythema nodosum, pyoderma gangrenosum and enteropathic arthritis.
Cirrhosis causes portal hypertension, hypoalbuminemic edema, coagulopathy, thrombocytopenia and altered drug metabolism, all of which raise perioperative risk in foot and ankle surgery.
Diabetes mellitus is diagnosed with an HbA1c of at least 6.5%, fasting glucose of at least 126 mg/dL, 2-hour OGTT glucose of at least 200 mg/dL, or random glucose of at least 200 mg/dL with symptoms.
Graves disease can cause pretibial myxedema (infiltrative dermopathy of the shins) and thyroid acropachy; hypothyroidism causes myxedema and tarsal tunnel syndrome.
Acromegaly enlarges the feet and increases shoe size; a lateral radiograph heel-pad thickness above about 22–23 mm is a classic sign.
9.4 Gastrointestinal, Hepatobiliary & Endocrine Pathology
The pathology outline lists the gastrointestinal system, the hepatic and extrahepatic biliary system and the endocrine system as separate categories. Diabetic microangiopathy, neuropathy and Charcot foot are covered in 8.1 and 8.3. This section covers the remaining disorders and their foot and leg signs.
Esophagus & Stomach
- GERD and Barrett esophagus: intestinal metaplasia (7.1) increases the risk of esophageal adenocarcinoma; squamous cell carcinoma relates to smoking and alcohol.
- Helicobacter pylori gastritis: causes peptic ulcers, gastric adenocarcinoma and MALT lymphoma; eradication heals ulcers.
- NSAID-induced ulcers: loss of COX-1 prostaglandins (11.3); the risk rises with age, corticosteroids and anticoagulants.
Small Bowel & Malabsorption
Celiac disease is a gluten-triggered (HLA-DQ2/DQ8) T-cell enteropathy with villous atrophy and positive tissue transglutaminase IgA. Malabsorption leads to iron, folate, vitamin D and calcium deficiency, causing osteomalacia and stress fractures. Its skin marker is dermatitis herpetiformis (IgA at the dermal papillae).
Inflammatory Bowel Disease
| Feature | Crohn disease | Ulcerative colitis |
|---|---|---|
| Distribution | Mouth to anus, skip lesions, terminal ileum common | Continuous from the rectum proximally |
| Depth | Transmural: fistulas, strictures | Mucosal and submucosal |
| Histology | Noncaseating granulomas | Crypt abscesses, pseudopolyps |
| Associations | Oxalate stones, B12 deficiency (ileal disease) | Primary sclerosing cholangitis (p-ANCA), colon cancer |
Extraintestinal manifestations in the foot and leg:
- Erythema nodosum: tender red nodules on the shins (septal panniculitis). It tracks bowel activity and is also seen with sarcoidosis, streptococcal infection and pregnancy.
- Pyoderma gangrenosum: a rapidly enlarging ulcer with an undermined violaceous border, often on the leg. Pathergy means debridement makes it worse.
- Enteropathic arthritis: peripheral (large-joint, activity-related) and axial (HLA-B27-associated sacroiliitis) forms.
Colon
- Adenoma-carcinoma sequence: APC loss, then KRAS activation, then TP53 loss. A Lynch syndrome (mismatch repair) pathway also exists.
- Screening: average-risk screening begins at age 45 in current U.S. recommendations.
- Other disorders: diverticular disease; ischemic colitis at watershed areas (splenic flexure, rectosigmoid); Clostridioides difficile colitis after clindamycin, fluoroquinolones or cephalosporins.
Liver
| Disorder | Key features |
|---|---|
| Viral hepatitis | Hepatitis B and C can become chronic (serology in 6.2); HCV causes mixed cryoglobulinemia with palpable purpura of the legs |
| Alcohol-associated liver disease | AST:ALT ratio usually above 2; Mallory-Denk bodies |
| Metabolic dysfunction-associated steatotic liver disease (MASLD, formerly NAFLD) | Linked to obesity, insulin resistance and diabetes |
| Hereditary hemochromatosis | HFE C282Y; arthropathy of the 2nd and 3rd MCP joints and ankles, CPPD, diabetes, skin bronzing |
| Wilson disease | ATP7B; low ceruloplasmin, Kayser-Fleischer rings |
| Hepatocellular carcinoma | Cirrhosis, HBV, HCV, aflatoxin; elevated AFP |
| Drug-induced injury | Acetaminophen (zone 3 necrosis; N-acetylcysteine); terbinafine and azoles (11.2) |
Cirrhosis (bridging fibrosis with regenerative nodules) causes:
- Portal hypertension with varices, splenomegaly (and thrombocytopenia) and ascites
- Hypoalbuminemia with pedal edema
- Coagulopathy (raised INR from reduced clotting factor synthesis)
- Hepatic encephalopathy (ammonia)
- Altered drug metabolism, gynecomastia, spider angiomata and palmar erythema
Each of these changes raises the bleeding, infection and anesthesia risk of elective foot surgery.
Gallbladder, Biliary Tree & Pancreas
- Cholelithiasis: cholesterol stones (female sex, obesity, pregnancy, rapid weight loss) or pigment stones (hemolysis, as in sickle cell disease).
- Acute cholecystitis (Murphy sign); choledocholithiasis with conjugated hyperbilirubinemia; ascending cholangitis (Charcot triad: fever, jaundice, right upper quadrant pain).
- Primary biliary cholangitis: antimitochondrial antibodies, women. Primary sclerosing cholangitis: associated with ulcerative colitis.
- Acute pancreatitis: gallstones or alcohol; elevated lipase; peripancreatic fat necrosis (7.1).
- Pancreatic adenocarcinoma: painless jaundice with a palpable gallbladder (Courvoisier sign), and Trousseau syndrome (migratory superficial thrombophlebitis, 7.3).
Endocrine Pathology
Diabetes Mellitus
| Criterion | Diagnostic threshold |
|---|---|
| HbA1c | 6.5% or higher |
| Fasting plasma glucose | 126 mg/dL or higher |
| 2-hour glucose on 75-g oral glucose tolerance test | 200 mg/dL or higher |
| Random plasma glucose with classic symptoms | 200 mg/dL or higher |
Without unequivocal hyperglycemia, an abnormal result is confirmed with repeat testing. Type 1 diabetes is autoimmune beta-cell destruction with ketosis risk. Type 2 diabetes combines insulin resistance with progressive beta-cell failure. Diabetic ketoacidosis (anion-gap acidosis, 16.2) mainly affects type 1, and the hyperosmolar hyperglycemic state affects older type 2 patients. Chronic complications are microvascular (retinopathy, nephropathy, neuropathy) and macrovascular (coronary, cerebral and peripheral artery disease).
Thyroid, Parathyroid, Adrenal & Pituitary
| Disorder | Pathology | Lower extremity clue |
|---|---|---|
| Graves disease | TSH-receptor stimulating antibodies | Pretibial myxedema (infiltrative dermopathy of the shins) and thyroid acropachy; heat intolerance; onycholysis |
| Hashimoto thyroiditis | Anti-TPO antibodies, lymphocytic infiltrate | Myxedema; tarsal tunnel syndrome; delayed relaxation of the Achilles reflex |
| Papillary thyroid carcinoma | Most common thyroid cancer; psammoma bodies | |
| Primary hyperparathyroidism | Usually a single adenoma | "Stones, bones, groans, moans"; brown tumors; CPPD |
| Cushing syndrome | Excess cortisol (most often from exogenous steroids) | Proximal myopathy, osteoporosis, thin skin, poor wound healing |
| Addison disease | Autoimmune adrenal destruction | Hyperpigmentation (including palmar creases), hypotension, hyperkalemia |
| Pheochromocytoma | Catecholamine-secreting tumor | Episodic hypertension; preoperative alpha-blockade (10.3) |
| Acromegaly | Growth hormone-secreting pituitary adenoma (IGF-1 elevated) | Enlarging hands and feet, increasing shoe size, thick heel pad (lateral radiograph thickness above about 22–23 mm), arthropathy |
Multiple endocrine neoplasia syndromes cluster tumors (MEN1: parathyroid, pituitary, pancreas; MEN2: medullary thyroid carcinoma and pheochromocytoma).
A patient with active ulcerative colitis has a rapidly enlarging, very painful leg ulcer with an undermined violaceous border that worsened after sharp debridement. What is the most likely diagnosis?
Venous stasis ulcer from incompetent perforating veins
Erythema nodosum progressing to necrosis
Pyoderma gangrenosum with pathergy
Ischemic ulcer from tibial artery occlusion
Which result alone, without symptoms, meets the diagnostic threshold for diabetes mellitus but should be confirmed by repeat testing?
HbA1c of 6.7%
Random plasma glucose of 165 mg/dL
Fasting plasma glucose of 118 mg/dL
Two-hour glucose of 182 mg/dL on a 75-g oral glucose tolerance test
A 47-year-old reports that his shoe size has increased by two sizes over five years. He has coarse facial features and large hands, and a lateral foot radiograph shows a heel-pad thickness of 29 mm. Which test best screens for the underlying disorder?
Serum thyroid-stimulating hormone
Twenty-four-hour urinary metanephrines
Serum insulin-like growth factor 1 (IGF-1)
Antinuclear antibody titer
Sections you finish are checked off in the contents.