GI Flashcards
1
Q
What is achalasia?
A
A primary esophageal motility disorder due to degeneration of the myenteric plexus, characterized by: Aperistalsis of the esophageal body. Failure of LES relaxation (in >50% of cases). Increased LES pressure (>6 mmHg).
2
Q
What are the causes of achalasia?
A
Idiopathic. Adenocarcinoma of the proximal stomach. Chagas disease (Trypanosoma cruzi infection).
3
Q
What are the clinical features of achalasia?
A
Triad: Dysphagia (to liquids and solids), regurgitation, weight loss. Halitosis. Retrosternal chest pain. Complications: Aspiration pneumonia, bronchitis.
4
Q
How is achalasia diagnosed?
A
Chest X-ray: Dilated esophagus, air-fluid levels, absence of gastric air bubble. Barium swallow: Bird beak sign. Manometry (Gold Standard): Absence of peristalsis, failure of LES relaxation, increased LES tone. Endoscopy: To rule out malignancy.
5
Q
How is achalasia treated?
A
Medical: Nitroglycerin, sildenafil (PDE inhibitor), nifedipine (CCB) to decrease LES tone. Endoscopic: Balloon dilation (2% risk of perforation), Botox injection into LES. Surgical: Heller cardiomyotomy + fundoplication (to prevent reflux).
Higher risk of squamous cell carcinoma in both treated and untreated cases.
6
Q
How does systemic sclerosis affect the esophagus?
A
Smooth muscle layer is replaced by fibrous tissue. Chronic heartburn, esophageal dysmotility. History of scleroderma. Manometry: Low LES pressure, aperistalsis, esophageal hypomobility. Treatment: PPIs for reflux.
7
Q
What is diffuse esophageal spasm?
A
Loss of normal peristaltic coordination in the esophageal smooth muscle, causing simultaneous contractions of the esophageal body.
8
Q
What are the symptoms of diffuse esophageal spasm (DES)?
A
Substernal spastic chest pain, sudden onset, not related to exertion. Precipitated by drinking cold liquids. Dysphagia to both solids & liquids (NO regurgitation unlike achalasia).
9
Q
How is diffuse esophageal spasm (DES) diagnosed?
A
Barium swallow: Corkscrew esophagus. Manometry (Gold Standard): Spontaneous activity, repetitive waves, prolonged high-amplitude contractions, normal LES tone. Endoscopy: To rule out mass, stricture, esophagitis.
10
Q
How is diffuse esophageal spasm (DES) managed?
A
Medical therapy: Nitrates, calcium channel blockers. Severe cases: Esophageal myotomy from the aortic arch level to the stomach.
11
Q
What are the types of hiatal hernias?
A
Type I (Sliding hiatal hernia): Most common type. Gastroesophageal junction (GEJ) slides into the chest. Associated with GERD. Tx: Asymptomatic cases observed; symptomatic cases treated like GERD. Type II (Paraesophageal hernia): Fundus of stomach herniates, GEJ remains in place. Higher risk of incarceration/ischemia. Tx: Surgery if symptomatic (reduction, fundoplication, gastropexy). Type III: Combination of sliding & paraesophageal hernias. Type IV: involvement of other organs (colon, spleen, omentum).
12
Q
How is a hiatal hernia diagnosed?
A
Chest X-ray: Air in mediastinum. Contrast upper GI swallow (Gold Standard). CT scan for detailed anatomy.
13
Q
What are esophageal strictures and their causes?
A
Benign or acquired from esophageal injury. Causes: Long-standing GERD, radiotherapy, corrosive ingestion, prolonged NGT use.
14
Q
What are the symptoms of esophageal strictures?
A
Progressive dysphagia (first solids, then liquids) (unlike motility disorders).
15
Q
How is an esophageal stricture diagnosed?
A
Barium swallow (first test). Endoscopy (definitive test) to assess location, size, dispensability & rule out carcinoma.
16
Q
How is an esophageal stricture treated?
A
Endoscopic dilation + PPIs (if GERD is the cause). Complication: Esophageal rupture → pneumomediastinum.
17
Q
What are esophageal webs?
A
Thin non-circumferential mucosal membranes that partially obstruct the upper esophagus.
18
Q
What is Plummer-Vinson Syndrome?
A
A condition characterized by a triad of: Cervical esophageal web. Dysphagia. Iron deficiency anemia.
19
Q
What are the other symptoms of Plummer Vinson syndrome?
A
Intermittent dysphagia to solids. Glossitis, angular cheilitis, koilonychia, splenomegaly, and thyroid enlargement.
20
Q
What is the significance of Plummer-Vinson Syndrome?
A
Increases the risk of squamous cell carcinoma of the esophagus.
21
Q
How are esophageal webs diagnosed?
A
Barium swallow (preferred test) showing a thin mucosal shelf.
22
Q
How is Plummer Vinson Syndrome treated?
A
Iron replacement (rapid resolution of dysphagia). Endoscopic dilation if significant obstruction is present.
23
Q
What is a Schatzki ring?
A
A circumferential narrowing of the distal (lower) esophagus (at the esophagogastric junction).
24
Q
What causes Schatzki rings?
A
Chronic acid reflux (GERD). Hiatal hernia association.
25
What are the symptoms of Schatzki rings?
Intermittent dysphagia to solids. Symptoms worsen with large food boluses.
26
How are Schatzki rings diagnosed & treated?
Barium swallow (preferred test) showing a narrow ring-like structure in the distal esophagus. Tx: Endoscopic pneumatic dilation. Long-term PPI therapy if associated with GERD.
27
What is Zenker diverticulum?
False diverticulum (only mucosa + submucosa). Outpouching at the posterior pharyngeal constrictor muscles.
28
What are the symptoms of Zenker diverticulum?
Dysphagia, halitosis, regurgitation of undigested food. Gurgling. Mass in the neck. Aspiration pneumonia.
29
How is Zenker diverticulum diagnosed and treated?
Diagnosis: Barium swallow. Treatment: Surgical resection (no role for medical therapy).
30
What are the two main types of esophageal carcinoma?
Squamous Cell Carcinoma (SCC) – more common worldwide. Adenocarcinoma – more common in the United States.
31
Where does squamous cell carcinoma typically occur in the esophagus?
Upper and middle thirds of the esophagus.
32
What are the risk factors for squamous cell carcinoma?
Smoking. Chronic alcohol consumption. High dietary intake of nitrosamines (salted fish, smoked foods). Achalasia (chronic irritation from food stasis). History of caustic esophageal injury (lye ingestion). Geographic prevalence: More common in China, Iran, and Asia.
33
Where does esophageal adenocarcinoma typically occur?
Lower third of the esophagus.
34
What is the main risk factor for esophageal adenocarcinoma?
Barrett’s esophagus due to long-standing GERD.
35
What other risk factors contribute to esophageal adenocarcinoma?
Obesity (increases GERD risk). Smoking.
36
What are the symptoms of esophageal carcinoma?
Progressive dysphagia (first to solids, then to liquids). Weight loss. Retrosternal chest pain (due to local infiltration or food impaction). Hoarseness (recurrent laryngeal nerve involvement). Hematemesis.
37
How do squamous cell carcinoma and adenocarcinoma differ in presentation?
SCC patients: Typically have greater weight loss and more advanced disease at diagnosis. Adenocarcinoma patients: Often diagnosed earlier due to Barrett’s surveillance.
38
What is the best initial test for esophageal carcinoma?
Barium swallow (shows irregular stricture or filling defect).
39
What imaging is used to assess metastasis?
CT scan (detects metastases, especially to the liver and lungs). PET scan (more sensitive for detecting distant metastases).
40
What is the gold standard for confirming esophageal carcinoma?
Endoscopy with biopsy.
41
How is local tumor staging done?
Endoscopic ultrasound (assesses tumor depth and adjacent lymph node involvement).
42
Why is bronchoscopy performed in esophageal cancer patients?
To rule out tracheobronchial invasion.
43
What is the treatment approach for localized esophageal cancer?
Surgical resection with neoadjuvant chemotherapy +/- radiation therapy.
44
How is locally advanced esophageal cancer (without distant metastasis) treated?
Chemotherapy + radiation therapy.
45
How is metastatic esophageal cancer managed?
Palliative care (poor prognosis). Endoscopic dilation with balloon expansion. Laser and photodynamic therapy for symptomatic relief.
46
What is GERD?
Reflux of stomach contents (gastric acid, pepsin, bile) into the esophagus due to incompetent LES.
47
What are the symptoms of GERD?
Heartburn, regurgitation, dysphagia, epigastric discomfort after meals. Pain relieved by antacids, aggravated by lying down or leaning forward.
48
What are the causes of GERD?
GERD is caused by lower esophageal sphincter (LES) dysfunction, increased intra-abdominal pressure, and delayed gastric emptying. Contributing factors include hiatal hernia, obesity, pregnancy, and systemic diseases (e.g., scleroderma, diabetes). Certain foods (fatty foods, chocolate, caffeine, alcohol, spicy foods) and medications (TCAs, nitrates, calcium channel blockers, NSAIDs) can also relax the LES and worsen reflux.
49
What are the complications of GERD?
Schatzki’s ring (distal esophageal stricture). Barrett’s esophagus (intestinal metaplasia → adenocarcinoma risk). Peptic strictures (solid food dysphagia, requires dilation).
50
How is GERD diagnosed?
Clinical diagnosis; trial of PPIs for 2 weeks. 24-hour esophageal pH study (gold standard for confirming abnormal acid exposure). Barium study. Esophageal manometry. Upper endoscopy if alarm symptoms (weight loss, anemia, dysphagia).
51
How is GERD managed?
Lifestyle changes (weight loss, avoid eating before bed, elevate head, stop smoking/alcohol) + alginate-containing antacids. If antacids fail: H2 receptor blockers (ex: cimetidine, ranitidine). First-line: PPIs (omeprazole, esomeprazole). Metoclopramide (delay gastric emptying). Surgical: Nissen fundoplication (for refractory cases).
52
What is Barrett’s Esophagus?
A complication of long-standing GERD, characterized by intestinal metaplasia where the normal squamous epithelium of the distal esophagus is replaced by columnar epithelium with goblet cells. increases the risk of developing esophageal adenocarcinoma.
53
What causes Barrett’s Esophagus?
Chronic acid exposure from GERD leading to epithelial damage and metaplasia. Risk factors: Long-standing GERD. Obesity (increases intra-abdominal pressure). Smoking. Male sex. Age >50 years.
54
How is Barrett’s esophagus diagnosed?
Upper endoscopy (Gold Standard): Identifies salmon pink, velvety mucosa in the distal esophagus. Biopsy: Confirms intestinal metaplasia with goblet cells.
55
What is the progression of Barrett’s Esophagus?
Metaplasia (Barrett’s Esophagus). Low-grade dysplasia. High-grade dysplasia. Esophageal adenocarcinoma. 1% risk of adenocarcinoma per year. Higher risk in patients with dysplasia.
56
How is Barrett’s Esophagus managed?
High-dose PPI therapy (to reduce acid exposure). Endoscopic surveillance based on histologic findings: Metaplasia (without dysplasia): Rescope every 2-3 years. Low-grade dysplasia: Repeat biopsy in 6 months, while on high-dose PPI. High-grade dysplasia: Endoscopic mucosal resection (if visible lesion). Radiofrequency ablation is the preferred treatment. Close surveillance with biopsy.
57
What is Helicobacter pylori and what conditions is it associated with?
H. pylori is a Gram-negative, urease-producing, spiral-shaped bacterium found in the gastric antrum. It is associated with: Chronic active gastritis, Peptic ulcer disease (gastric & duodenal ulcers), Gastric cancer, Gastric B-cell lymphoma (MALT lymphoma).
58
How does H. pylori cause disease?
Increases gastric acid secretion by increasing gastrin and parietal cell mass while reducing somatostatin production. Disrupts the mucus protective layer. Reduces duodenal bicarbonate production. Produces virulence factors that damage the gastric epithelium.
59
How is H. pylori diagnosed?
Non-invasive tests: Serology (detects antibodies, but not useful for eradication confirmation), Urea breath test (diagnosis & eradication confirmation), Stool antigen test. Invasive test (endoscopic biopsy from antrum): Histology (silver stain), Rapid urease test (CLO test).
60
How is H. pylori treated?
Triple therapy (PPI-based, 14 days): Omeprazole + Metronidazole + Clarithromycin (twice daily), Omeprazole + Amoxicillin + Clarithromycin (twice daily). Quadruple therapy (if resistant cases): Bismuth chelate + Omeprazole + Metronidazole + Tetracycline.
61
What is peptic ulcer disease?
Loss of the mucosa and exposure of the submucosa in acid-bearing areas, typically in the stomach or proximal duodenum.
62
What are the causes of PUD?
H. pylori infection (most common), NSAIDs and aspirin (reduce mucosal prostaglandins), Other causes: Smoking, glucocorticoids, Zollinger-Ellison syndrome, vascular insufficiency, Crohn’s disease.
63
How do gastric and duodenal ulcers differ in acid production?
Gastric ulcers: Associated with decreased acid production. Duodenal ulcers: Associated with increased acid production.
64
What are the clinical features of PUD?
Burning epigastric pain (most common). Duodenal ulcers → worse at night & when hungry, relieved by food. Gastric ulcers → worse with food. Nausea, heartburn, flatulence. Complications: Perforation (anterior duodenal wall, air under diaphragm), Painless hemorrhage (upper GI bleed, gastroduodenal artery involvement), Gastric outlet obstruction (edema, scarring, projectile vomiting).
65
How is PUD diagnosed?
Non-invasive H. pylori testing (urea breath test, stool antigen). Endoscopy (if complications or alarm symptoms are present). Barium meal (if gastric outlet obstruction suspected).
66
How is PUD treated?
If H. pylori positive: Eradication therapy (confirmed by urea breath test or stool antigen). If H. pylori negative: Stop NSAIDs, start PPIs. Follow-up endoscopy for gastric ulcers (to exclude malignancy).
67
What is gastropathy, what causes it, and what are its symptoms?
Gastropathy is mucosal injury of the stomach without significant inflammation. Common causes include NSAIDs/aspirin (most common), alcohol, severe stress (stress ulcers), infections (CMV, HSV), renal disease, and liver disease. Symptoms include indigestion (dyspepsia), vomiting, and upper GI bleeding (hematemesis, melena).
68
How is gastropathy diagnosed and treated?
Diagnosis is made by endoscopy, which shows mucosal erosions and subepithelial hemorrhages without inflammation. Tx includes proton pump inhibitors (PPIs) to reduce acid exposure, stopping the offending agent (e.g., NSAIDs, alcohol).
69
What are the causes of gastritis?
H. pylori infection (most common), Autoimmune gastritis (pernicious anemia), Viral infections, Duodenogastric reflux.
70
What are the causes of gastropathy?
NSAIDs (most common), Alcohol, Severe stress (stress ulcers, Curling’s ulcers in burns), Renal/liver disease, Cytomegalovirus (CMV), herpes simplex virus (HSV).
71
How is gastritis diagnosed?
Histology from endoscopic gastric biopsy. Acute gastritis: Neutrophilic infiltration. Chronic gastritis: Mononuclear cell infiltration.
72
How is gastritis treated?
H. pylori eradication (if positive). PPI therapy & removal of offending cause.
73
What are gastric polyps, their types, and how are they managed?
Gastric polyps are abnormal growths in the stomach lining, often detected incidentally during endoscopy. They are usually benign but may have malignant potential. Types include: Hyperplastic polyps → Associated with chronic gastritis, have a minor risk of malignancy, Adenomatous polyps → Rare but premalignant, found mostly in the antrum; all should be removed due to the risk of cancer, Fundic gland polyps → Benign, common with prolonged PPI use, rarely progress to malignancy. Management: Endoscopic removal of adenomatous and large polyps, followed by histologic examination to rule out malignancy.
74
What are the risk factors for gastric cancer?
H. pylori infection (leading to atrophic gastritis and intestinal metaplasia), Pernicious anemia, Smoking, Diets low in fruits/vegetables, high in salted/smoked/preserved foods, History of gastric cancer or previous partial gastrectomy.
75
What are the types of gastric cancer?
Intestinal type: Localized ulcerated lesion with rolled edges. Diffuse type: Extensive submucosal spread (linitis plastica), signet ring cells.
76
What are the clinical features of gastric cancer?
Epigastric pain (most common, similar to PUD). Weight loss, nausea, early satiety, anemia, hematemesis. Palpable epigastric mass, Sister Mary Joseph nodule (umbilical metastasis). Virchow’s node (left supraclavicular lymph node). Metastatic signs: Hepatomegaly, ascites, acanthosis nigricans, dermatomyositis. Tumors near to the pylorus present with outflow obstruction: vomiting. Tumors near to the cardia present with vomiting and dysphagia.
77
How is gastric cancer diagnosed?
Gastroscopy with biopsy (gold standard). CT scan, endoscopic ultrasound, laparoscopy (staging).
78
What is the treatment for gastric cancer?
Surgical resection (if operable). Adjuvant chemotherapy (for advanced disease). Chemotherapy alone (for unresectable cases).
79
What is the prognosis of gastric cancer?
Overall 5-year survival: 10%. 5-year survival after curative surgery: 50%.
80
What is GIST?
A slow-growing mesenchymal tumor of the GI tract, most commonly found in the stomach & proximal small intestine.
81
How is GIST diagnosed?
Histology: Spindle cells, CD117 (c-KIT) mutation, PDGFRA mutation.
82
How is GIST treated?
Surgical resection (curative for localized tumors). Imatinib (tyrosine kinase inhibitor) for advanced or metastatic cases.
83
What is gastric lymphoma, its causes, and how is it managed?
Gastric lymphoma is a malignancy of the stomach’s lymphoid tissue, most commonly arising from MALToma. It presents similarly to gastric cancer with epigastric pain, weight loss, nausea, and GI bleeding. The majority are associated with Helicobacter pylori infection. Diagnosis is made via endoscopic biopsy. Tx depends on the type: H. pylori-associated MALT lymphoma can regress with H. pylori eradication therapy, while advanced or non-MALT lymphomas require chemotherapy, radiation, or surgery.
84
What is celiac disease and how does it affect the intestine?
Celiac disease is an autoimmune disorder triggered by gluten (found in wheat, rye, and barley), leading to villous atrophy, crypt hyperplasia, and increased intraepithelial lymphocytes in the small intestine (mainly jejunum and distal duodenum). It improves with a gluten-free diet and relapses when gluten is reintroduced.
85
What is the pathogenesis of celiac disease?
Gliadin (toxic gluten component) is resistant to protease degradation. Gliadin damages the epithelial barrier, allowing it to be deaminated by tissue transglutaminase (tTG), which increases its immunogenicity. Gliadin is presented via HLA DQ2/DQ8 to activate T-cells, leading to an immune response and intestinal damage.
86
What are the clinical features of celiac disease?
Two peaks of onset: Infancy (after weaning onto gluten-containing foods) & adulthood (fifth decade). Non-specific symptoms: Tiredness, malaise, diarrhea, steatorrhea, abdominal pain, anorexia, weight loss. Physical signs: Related to anemia and nutritional deficiencies. Increased incidence of autoimmune diseases (e.g., Type 1 DM, thyroid disease).
87
How is celiac disease diagnosed?
Serology: IgA tissue transglutaminase (tTG) antibodies (best test, false negatives in IgA deficiency). Endoscopic duodenal biopsy (gold standard): Villous atrophy, crypt hyperplasia, increased intraepithelial lymphocytes. Bone densitometry (DEXA scan) is done at diagnosis due to increased osteoporosis risk.
88
What is the management of celiac disease?
Lifelong gluten-free diet. Correct nutritional deficiencies (iron, folate, vitamin B12). Monitor with serology (antibody disappearance suggests compliance). Pneumococcal vaccine recommended due to hyposplenism risk.
89
What are the complications of untreated celiac disease?
Enteropathy-associated T-cell lymphoma (EATL) and small bowel adenocarcinoma. Esophageal cancer (squamous cell carcinoma). Increased risk of osteoporosis.
90
What is dermatitis herpetiformis and its relation to celiac disease?
A chronic, itchy, vesicular skin rash with IgA deposition at the dermo-epidermal junction. It is associated with celiac disease and improves with a gluten-free diet and dapsone.
91
What is tropical sprue and how does it differ from celiac disease?
A progressive small intestinal disorder seen in residents or visitors to tropical regions (Asia, Caribbean, South Africa) with villous atrophy (similar to celiac but affects jejunum and ileum more severely). It is likely caused by an infectious agent (e.g., Giardia).
92
What are the symptoms of tropical sprue?
Chronic diarrhea, steatorrhea, weight loss. Megaloblastic anemia (due to folate ± vitamin B12 deficiency).
93
How is tropical sprue diagnosed and treated?
Diagnosis: Small bowel biopsy (villous atrophy), exclusion of parasitic infections. Treatment: Folic acid + tetracycline for 3–6 months.
94
What is Whipple’s disease and how does it present?
A rare bacterial infection caused by Tropheryma whipplei, affecting the small intestine and multiple organ systems. Symptoms include: Fever, steatorrhea, abdominal pain. Lymphadenopathy, arthritis, neurological symptoms (seizures, dementia).
95
How is Whipple’s disease diagnosed and treated?
Diagnosis: PAS-positive macrophages in intestinal biopsy, PCR for T. whipplei. Treatment: Cotrimoxazole for 1 year.
96
What is bacterial overgrowth syndrome and what causes it?
Excessive bacterial growth in the small intestine, causing bile salt deconjugation and malabsorption due to stasis from motility disorders, surgical blind loops, diverticula, or bowel infiltration.
97
What are the symptoms of bacterial overgrowth?
Steatorrhea and vitamin B12 deficiency.
98
How is bacterial overgrowth diagnosed and treated?
Diagnosis: Hydrogen breath test (early hydrogen peak). Small intestine aspirate and culture (gold standard). Treatment: Antibiotics (tetracycline, metronidazole) and correction of the underlying cause.
99
What is small bowel adenocarcinoma and what are its risk factors?
Small bowel adenocarcinoma is a rare but aggressive malignancy most commonly affecting the duodenum. Risk factors include familial syndromes (FAP, Lynch syndrome), chronic inflammation (Crohn’s disease, celiac disease), dietary factors (high red meat/alcohol consumption), smoking, and prior radiation exposure.
100
What are the symptoms and how is small bowel adenocarcinoma diagnosed?
Symptoms include abdominal pain (most common), weight loss, GI bleeding (iron deficiency anemia), bowel obstruction (nausea, vomiting), and jaundice (if bile duct involvement). Diagnosis is made using CT enterography, capsule endoscopy, and endoscopic biopsy (gold standard).
101
How is small bowel adenocarcinoma treated?
Surgical resection is the primary curative option for localized cases. Adjuvant chemotherapy is used for advanced disease, and palliative treatment is considered for metastatic cases.
102
What is small bowel lymphoma, and what are its risk factors and symptoms?
Small bowel lymphoma is a primary malignancy of lymphoid tissue, most commonly affecting the ileum due to its high concentration of (GALT). Symptoms include abdominal pain, chronic diarrhea, weight loss, GI bleeding, and bowel obstruction in advanced cases.
103
How is small bowel lymphoma diagnosed and treated?
Nodularity and thickening of the bowel wall on contrast studies and CT. CT scan also shows associated mesenteric adenopathy. Treatment is by surgical resection with subsequent chemotherapy and/or radiation.
104
What is Zollinger-Ellison syndrome and how does it present?
A gastrinoma (pancreatic tumor) that secretes excessive gastrin, leading to: Refractory peptic ulcers (multiple, duodenal, atypical locations). Chronic diarrhea (acid-induced inactivation of pancreatic enzymes). Associated with MEN1.
105
How is Zollinger-Ellison syndrome diagnosed and treated?
Diagnosis: Fasting gastrin levels >1000. Secretin stimulation test (paradoxical gastrin increase). Tumor localization (CT, MRI, endoscopic ultrasound). Liver most common site of metastasis. Treatment: High-dose PPIs to reduce acid. Surgical resection if localized. Octreotide. For MEN-1 associated cases, surgery is not recommended.
106
What are carcinoid tumors and carcinoid syndrome?
Neuroendocrine tumors, from intestinal entero-chromaffin cells (serotonin producing kulchitsky cells) (most common in the ileum) that secrete serotonin, histamine, and bradykinin, causing carcinoid syndrome if liver metastases bypass metabolism.
107
What are the symptoms of carcinoid syndrome?
Flushing, wheezing, diarrhea, right-sided valvular fibrosis (tricuspid regurgitation, pulmonary stenosis). Left side is safe bc of monoamine oxidase.
108
How is carcinoid syndrome diagnosed and treated?
Diagnosis: High urinary 5-HIAA (serotonin breakdown product). Serum chromogranin or serotonin. US for metastasis. Treatment: Somatostatin analogues / octreotide / 5-HT antagonists (cyproheptadine). Surgical resection if feasible.
109
What is IBS and how does it present?
A functional GI disorder with chronic abdominal pain relieved by defecation, alternating diarrhea and constipation, and worsened by stress. There is no weight loss or blood in stool.
110
What is inflammatory bowel disease (IBD), and what are its types?
IBD is a group of chronic systemic diseases involving intestinal inflammation. The types include: Crohn’s disease (CD): Can affect the entire GI tract (mouth to anus), commonly ileocecal region. Ulcerative colitis (UC): Affects only the colon, starting from the rectum and extending proximally. Indeterminate colitis: Features of both CD and UC. Microscopic colitis: Chronic diarrhea without macroscopic inflammation (includes lymphocytic and collagenous colitis).
111
What are the risk factors for IBD?
Genetic factors: Stronger for CD than UC, HLA-B27 association (IBD + ankylosing spondylitis), CARD15 (NOD2) gene mutation (ileocecal CD). Environmental factors: Smoking: Worsens CD, but protects against UC. NSAIDs: Trigger flares in both UC & CD. Breastfeeding: Protective against IBD. Appendectomy: Decreases UC risk. Stress & depression: associated w/ relapse. Hygiene hypothesis: Low CD risk. Immune response: Abnormal response to luminal antigens (bacteria) in genetically susceptible individuals.
112
How do Crohn’s disease and ulcerative colitis differ?
Location: CD: Can affect the entire GI tract, commonly ileocecal region, rectal sparing is common. UC: Limited to the colon, starts in rectum and extends proximally. Macroscopic Features: CD: 'Skip lesions' (discontinuous involvement), deep ulcers, cobblestone appearance. UC: Continuous inflammation, red mucosa, ulcers, pseudopolyps. Microscopic Features: CD: Transmural inflammation (all layers), non-caseating granulomas (50%). UC: Superficial inflammation (mucosa only), crypt abscesses, goblet cell depletion.
113
What are the symptoms of Crohn’s disease and ulcerative colitis?
Crohn’s disease (CD): Diarrhea (steatorrhea if small bowel, bloody if colon), abdominal pain, weight loss. Perianal disease (fissures, fistulas, abscesses) in 25% of cases. Acute CD may mimic appendicitis (right iliac fossa pain). Ulcerative colitis (UC): Diarrhea with blood and mucus. Lower abdominal pain, urgency, tenesmus (proctitis). Severe disease → risk of toxic megacolon (colonic dilation >6 cm, risk of perforation).
114
What are the extraintestinal manifestations of IBD?
Eyes: Uveitis, episcleritis, conjunctivitis. Joints: Arthralgia, arthritis, ankylosing spondylitis. Skin: Erythema nodosum, pyoderma gangrenosum. Hepatobiliary: Fatty liver, primary sclerosing cholangitis, gallstones. Renal: Oxalate kidney stones (CD). Vascular: Increased risk of venous thrombosis. Aphthous ulcers mostly in Crohn's.
115
How is IBD diagnosed?
Blood tests: Anemia (chronic disease, iron deficiency, B12/folate deficiency), ↑ ESR, CRP, thrombocytosis. Stool tests: Rule out infections (C. difficile, Yersinia mimics CD). Colonoscopy + biopsy (gold standard): Identifies extent and severity. Imaging: Barium follow-through (CD): 'String sign' (deep ulceration and narrowing) mostly in Crohn's. MRI/CT scan: Perianal CD, abscesses, strictures. Abdominal X-ray: Excludes perforation or toxic megacolon.
116
How is Crohn’s disease treated?
Inducing remission: Corticosteroids (oral/IV prednisolone). Budesonide for ileocecal CD (less systemic toxicity). Metronidazole & ciprofloxacin for perianal CD. Maintaining remission: Azathioprine (AZA), mercaptopurine (6-MP) (require TPMT enzyme testing). Methotrexate (if resistant to AZA/6-MP). Anti-TNF therapy (infliximab) for refractory cases & perianal disease.
117
How is ulcerative colitis treated?
Mild/moderate disease: 5-ASA (sulfasalazine, mesalamine) – rectal for proctitis, oral for extensive colitis. Prednisolone (if 5-ASA fails). Severe disease: Oral prednisone. Biologics (anti-TNF agents like infliximab). Severe & symptomatic: Cyclosporine / Hydrocortisone / anti-TNF alpha. Surgery (colectomy) if medical therapy fails.
118
What is the cancer risk in IBD, and how is it managed?
Colorectal cancer risk increases after 10 years of extensive colitis (UC or CD). High-risk patients (severe colitis, primary sclerosing cholangitis, family history) need colonoscopy every 1 year. Moderate risk: Colonoscopy every 3–5 years. Colectomy is recommended if high-grade dysplasia is found.
119
What is ischemic colitis, and how does it present?
Ischemic colitis is intestinal ischemia due to reduced blood flow, often in elderly patients. It commonly affects watershed areas (splenic flexure, cecum). Risk factors: Atherosclerosis, AAA repair, thrombophilia, vasculitis, cocaine abuse. Symptoms: Abdominal pain, rectal bleeding, possible shock. Diagnosis: Abdominal X-ray (thumbprinting, pneumatosis). Treatment: IV fluids, antibiotics (if moderate/severe), surgery for necrosis.
120
What are the causes of constipation?
Dietary/lifestyle: Low fiber, immobility. Endocrine: Hypothyroidism, hypercalcemia, diabetes. Neurological: Parkinson’s, spinal cord lesions. Medications: Opiates, CCBs, TCAs, anticholinergics, iron supplements. Alarm symptoms (require colonoscopy): Rectal bleeding, anemia, recent onset in older adults.
121
What are the types of chronic diarrhea and their causes?
Fatty diarrhea: Celiac disease, pancreatic insufficiency, Whipple’s disease. Inflammatory diarrhea: IBD, ischemic colitis, chronic infections. Watery diarrhea: Osmotic (stops with fasting): Lactose intolerance, malabsorption. Secretory (persists during fasting): VIPoma, bile salt diarrhea, microscopic colitis.
122
What are the morphological types of colorectal polyps?
Sessile (flat) and Pedunculated (on a stalk).
123
What are the histological types of colorectal polyps?
Inflammatory: Pseudopolyp seen in UC.
Hyperplastic: Benign overgrowth, no malignant potential, common in elderly.
Serrated: Pre-malignant.
Adenomatous: Pre-malignant (subtypes: villous, tubulovillous, tubular).
Hamartomatous: Normal tissue in an abnormal configuration (e.g., juvenile polyps, Peutz–Jeghers polyps).
124
What is the risk of cancer in different types of adenomatous polyps?
Villous: 40% risk.
Tubulovillous: 20% risk.
Tubular: 5% risk (most common).
125
What are the signs and symptoms of colorectal polyps?
Often asymptomatic (most common).
Melena, hematochezia, occult bleeding.
Obstruction, mucus, or change in bowel habits (e.g., secretory diarrhea).
126
What are high-risk features for malignancy in a polyp?
Size >2 cm.
Villous histology.
Severe atypia.
127
What is the treatment for colorectal polyps?
Colonoscopic resection and follow-up surveillance colonoscopy based on histology and size:
>2 cm, >2 polyps, villous component → Repeat in 3 years.
<2 cm, 1 or 2 polyps, tubular histology → Repeat in 5 years.
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What are the genetic pathways involved in colorectal cancer development?
Adenoma-carcinoma sequence (75% cases): Stepwise accumulation of mutations (APC → k-ras → p53).
Microsatellite instability: Defective DNA mismatch repair (e.g., Lynch syndrome).
Serrated methylation pathway: Hypermethylation of DNA promoter regions.
129
What are the risk factors for colorectal cancer?
Increasing age (>40, peak 60–65 years).
Family history (strongest after age).
Personal history of adenomatous polyps, CRC, breast/gonadal cancer.
African American race (higher rates and mortality).
Diabetes and acromegaly (insulin & IGF-1 promote colonic mucosal growth).
Smoking, alcohol, high-fat/low-fiber diet, red meat consumption.
Neoplastic/Adenomatous polyps (especially if >1 cm, villous, multiple).
Inflammatory bowel disease (especially ulcerative colitis).
Genetic predisposition (FAP, HNPCC).
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How does colorectal cancer present?
Right-sided tumors: Occult blood loss, iron deficiency anemia, palpable mass (advanced).
Left-sided tumors: Obstruction, hematochezia.
Rectal tumors: Rectal bleeding, obstruction, alternating diarrhea & constipation, tenesmus.
Systemic signs: Unexplained weight loss, fatigue, night sweats.
20% present with metastases (common sites: liver, lungs, peritoneum, lymph nodes).
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What investigations are done for colorectal cancer?
CBC: Microcytic anemia.
Fecal occult blood test (FOBT): Positive in early cases.
CEA tumor marker: Prognostic but not diagnostic (>5 ng/mL indicates poor prognosis).
Colonoscopy (Gold standard): Localization, biopsy, polyp removal.
CT colonography (if colonoscopy unavailable).
Staging: CT chest/abdomen/pelvis, MRI, endoanal ultrasound for rectal cancer.
132
What are the surgical treatment options for colorectal cancer?
Right-sided tumors → Right hemicolectomy.
Mid-transverse colon tumors → Extended right hemicolectomy.
Left-sided tumors → Left hemicolectomy.
Sigmoid tumors → Sigmoid colectomy.
Rectal cancer (Stage 2 & 3) → Neoadjuvant chemoradiation, surgical resection, adjuvant chemotherapy.
Stage 4 (Metastatic) → Palliative chemotherapy, liver metastasis resection if ≤3 mets.
133
What are the colorectal cancer screening guidelines?
Routine screening: Every 10 years starting at age 45.
Family history (1 affected member): Start 10 years before their diagnosis or at age 40 (whichever is younger), then every 5 years.
Previous adenomatous polyp: Colonoscopy every 3–5 years.
Lynch syndrome (HNPCC): Start at age 25, repeat every 1–2 years.
FAP: Start at age 12, annually.
Peutz-Jeghers syndrome: Start at age 8, every 3 years.
IBD: Colonoscopy 8–10 years after diagnosis, then every 1–5 years based on risk factors.
134
What is Familial Adenomatous Polyposis (FAP)?
Autosomal dominant (APC gene mutation, chromosome 5).
Hundreds to thousands of colorectal adenomas by age 20.
100% CRC risk without prophylactic colectomy.
Increased risk of extracolonic malignancies (bile duct, pancreas, stomach, thyroid).
Variants:
Turcot’s syndrome: Polyps + CNS tumors (gliomas).
Gardner’s syndrome: Polyps + osteomas, epidermal cysts.
135
What is Lynch Syndrome (HNPCC)?
Autosomal dominant, mutation in mismatch repair genes (MLH1, MSH2, etc.).
Accelerated adenoma-to-carcinoma progression (right-sided cancers).
Associated extracolonic cancers (endometrial, ovarian, gastric, urinary tract).
Variants:
Lynch I: Right-sided colon cancer.
Lynch II: sam was Lynch I but w/ additional risk for extracolonic cancers. (Breast, uterus, ovaries, cervix)
136
What is Peutz–Jeghers Syndrome?
Autosomal dominant, mutation in STK11 (LKB1) gene.
Multiple hamartomatous polyps throughout the GI tract.
Mucocutaneous pigmentation (lips/buccal mucosa/perioral region/palms/soles).
Increased risk of GI and extra-GI malignancies (colon/pancreas/breast/lung).
Screening: Colonoscopy every 3 years from age 8.
137
What is jaundice?
Jaundice is the yellow discoloration of the skin and sclera due to elevated total bilirubin (>3 mg/dL or 50 micromol/L).
138
How is bilirubin metabolized in the body?
Senescent RBCs are broken down in the reticuloendothelial system, releasing unconjugated bilirubin. Unconjugated bilirubin binds to albumin for transport to the liver. In the liver, uridine glucuronosyltransferase (UGT) conjugates bilirubin, making it water-soluble. Conjugated bilirubin is excreted into the bile, reaching the duodenum. Bacteria convert it into urobilinogen, which is oxidized into urobilin and stercobilin (gives stool its color). Some urobilinogen is reabsorbed and excreted in urine.
139
What are the three types of jaundice?
Pre-hepatic (Hemolytic/Acholuric) → Increased unconjugated bilirubin. Causes: Hemolysis, Gilbert syndrome, Crigler-Najjar syndrome. Dark urine, dark stool, increased AST. Hepatic (Hepatitis-related) → Increased both conjugated & unconjugated bilirubin. Causes: Hepatitis (viral, autoimmune, drug-induced). Dark urine, increased ALT & AST. Post-hepatic (Obstructive/Surgical/Painful) → Increased conjugated bilirubin. Causes: Gallstones, pancreatic head tumor, periampullary tumors. Dark urine, pale stools, pruritus, nausea, high ALP & GGT >> AST/ALT.
140
What are key investigations for jaundice?
Liver biochemistry: ALT (liver-specific), AST, ALP, GGT (cholestasis). Liver function tests: Albumin (low = liver failure), PT/INR (prolonged = liver failure). Antibodies: Anti-smooth muscle antibodies: Autoimmune hepatitis. Anti-mitochondrial antibodies: Primary biliary cirrhosis. Anti-neutrophil cytoplasmic antibodies (p-ANCA): Primary sclerosing cholangitis. Immunoglobulins: IgG (autoimmune hepatitis), IgA (alcoholic hepatitis), IgM (PBC).
141
What are the key features of Hepatitis A?
Incubation period: 2-6 weeks. Transmission: Fecal-oral (contaminated food or water). Symptoms: Fever, malaise, headache, nausea, vomiting, jaundice, RUQ pain, hepatomegaly, dark urine. Severity: Mild, usually self-limiting. Chronicity: 0% (no chronic infection). Associated complications: Rarely fulminant hepatitis. Diagnosis: Anti-HAV IgM (acute), Anti-HAV IgG (past infection or vaccination). Prevention: Hepatitis A vaccine, post-exposure immunoglobulin.
142
What are the key features of Hepatitis B?
Incubation period: 1-5 months. Transmission: Sexual > Parenteral (IV drug use, blood transfusions). Symptoms: Flu-like symptoms, jaundice, dark urine, joint pain, rash, RUQ pain, hepatomegaly. Severity: Occasionally severe. Chronicity: 5-10% develop chronic infection. Complications: Cirrhosis, hepatocellular carcinoma (HCC). Serology: HBsAg (Active infection). Anti-HBs (Immunity from past infection or vaccination). HBeAg (High infectivity). Anti-HBe (Low infectivity). Anti-HBc IgM (Acute infection). Anti-HBc IgG (Chronic or past infection). Prevention: Hepatitis B vaccine, post-exposure prophylaxis with HBIG. Treatment: Interferon, Tenofovir, Entecavir (for chronic cases).
143
What are the key features of Hepatitis C?
Incubation period: 2-6 months. Transmission: Parenteral > Sexual (IV drug use, blood transfusions). Symptoms: Often asymptomatic, mild jaundice, fatigue, nausea. Severity: Usually subclinical. Chronicity: 80% develop chronic infection. Complications: Cirrhosis, hepatocellular carcinoma (HCC). Diagnosis: Anti-HCV antibodies, HCV RNA (PCR test for active infection). Treatment: Direct-acting antivirals (DAAs) like Sofosbuvir and Ledipasvir. Prevention: No vaccine available, avoid risky behaviors (IV drug use, unsafe sex).
144
What are the key features of Hepatitis D?
Incubation period: 1-3 months. Transmission: Parenteral, sexual (requires Hepatitis B co-infection). Symptoms: Similar to Hepatitis B, more severe disease progression. Chronicity: 5% (occurs mainly in co-infection with Hep B). Complications: Rapid progression to cirrhosis, high risk of hepatocellular carcinoma (HCC). Diagnosis: Anti-HDV (anti delta) IgM and IgG, HDV RNA (PCR test). Prevention: Hepatitis B vaccination (since HDV requires HBV to infect). Treatment: Interferon-alpha (limited effectiveness).
145
What are the key features of Hepatitis E?
Incubation period: 3-8 weeks. Transmission: Fecal-oral (contaminated water, undercooked meat). Symptoms: Similar to Hepatitis A (fever, malaise, jaundice, nausea, dark urine). Severity: Usually mild, but severe in pregnant women (10-20% mortality). Chronicity: 0% (except in immunocompromised patients). Complications: Fulminant hepatitis in pregnancy. Diagnosis: Anti-HEV IgM and IgG, HEV RNA (PCR test). Prevention: Avoid contaminated water and food. Treatment: Supportive care, no specific antiviral therapy.
146
What are the features of autoimmune hepatitis?
More common in young/middle-aged women. Associated with other autoimmune diseases (e.g., thyroiditis, pernicious anemia). Hypergammaglobinemia, High IgG, circulating autoantibodies, and interface hepatitis.
147
What are the types of autoimmune hepatitis?
Type 1: Occurs in young women, associated with ANA, anti-smooth muscle, and p-ANCA antibodies. Type 2: Occurs in children, associated with liver/kidney microsomal antibodies (LKM) and anti-soluble liver antigen.
148
How is autoimmune hepatitis treated?
Prednisolone (30 mg/day, then taper to 10-15 mg). Azathioprine (lifelong therapy). Ciclosporin, Tacrolimus, Mycophenolate if resistant.
149
What are the risk factors for NAFLD?
Obesity, Type 2 diabetes, hyperlipidemia, hypertension, steroids. NAFLD has increased risk of HCC.
150
What are the histological findings in NAFLD?
Histological changes= alcoholic liver injury. Range from simple fatty changes to & inflammation (NASH), fibrosis, cirrhosis.
151
How is NAFLD diagnosed?
Ultrasound: Detects fatty infiltration. Liver biopsy: Confirms NASH. Serum ferritin >1.5x normal: Associated with advanced fibrosis. High ALT > AST. HIGH GGT.
152
How is NAFLD managed?
Lifestyle changes: Weight loss (0.5-1 kg/week), exercise, control of cardiovascular risk factors. Orlistat (1 year use only) to prevent fat-soluble vitamin deficiency. Pioglitazone/Vitamin E (for biopsy-proven NASH). Bariatric surgery in morbid obesity.
153
What are the stages of alcoholic liver disease?
Fatty liver: Reversible, asymptomatic, hepatomegaly, AST:ALT <2. Alcoholic hepatitis: Jaundice, fever, ascites, hepatomegaly, AST:ALT >2. Alcoholic cirrhosis: Portal hypertension, liver failure, HCC.
154
What is the histological finding in alcoholic hepatitis?
Neutrophil infiltration, Mallory bodies, and centrilobular necrosis.
155
How is alcoholic liver disease managed?
Alcohol cessation. IV thiamine to prevent Wernicke’s encephalopathy. Nutritional support and vitamin supplementation.
156
How is alcoholic cirrhosis managed?
Treat complications. Salt restriction(≤2g/day). 6 monthly US for HCC. Hepatitis A & B vaccinations. Avoid NSAIDs/aspirin (as they can cause GI bleeding & renal impairment).
157
What is the definition of cirrhosis?
Cirrhosis is the necrosis of liver cells followed by fibrosis and nodule formation, leading to impairment of liver function and portal hypertension.
158
What are the most common causes of cirrhosis?
Worldwide: Hepatitis B & C. Western world: Alcohol. Other causes: NAFLD, autoimmune hepatitis, PBC, PSC, hemochromatosis, Wilson’s disease, α1-antitrypsin deficiency, Budd-Chiari syndrome, cystic fibrosis, metabolic storage diseases, certain drugs, and cryptogenic cirrhosis.
159
What are the pathological types of cirrhosis?
Micronodular cirrhosis: Small, uniform nodules (<3mm), often caused by alcohol or biliary disease. Macronodular cirrhosis: Larger, variable-sized nodules, often due to chronic viral hepatitis.
160
How is cirrhosis classified based on complications?
Compensated cirrhosis: No complications (e.g., no ascites, encephalopathy, or variceal hemorrhage). Decompensated cirrhosis: Presence of complications such as ascites, variceal bleeding, or hepatic encephalopathy.
161
What are the clinical features of cirrhosis?
Symptoms result from portal hypertension and liver failure: General: Fatigue, weight loss, malnutrition, muscle wasting, osteoporosis. Liver failure signs: Jaundice, palmar erythema, spider nevi, hepatosplenomegaly. Portal hypertension signs: Ascites, esophageal varices, caput medusae. Endocrine effects: Gynecomastia, testicular atrophy in men, amenorrhea in women.
162
What investigations are done for cirrhosis?
CBC: Thrombocytopenia, leukopenia, anemia. LFTs: Mildly elevated ALP and aminotransferases (ALT/AST). Coagulation: Prolonged PT/INR (indicates liver dysfunction). Electrolytes: Low sodium (due to impaired water clearance). Serum creatinine: Elevated if hepatorenal syndrome is present. AFP (α-fetoprotein): Elevated in hepatocellular carcinoma (>200 ng/mL suggests HCC). Imaging: Liver ultrasound to assess nodularity and portal vein patency, endoscopy for varices. Bone density (DXA scan): For osteoporosis screening.
163
How is cirrhosis managed?
Treat the underlying cause: Abstinence from alcohol for alcoholic cirrhosis. Venesection for hemochromatosis. Monitor for complications: HCC screening with AFP & ultrasound every 6 months. Endoscopy for esophageal varices screening. Liver transplantation: Indicated for end-stage cirrhosis. Vaccination: Influenza, pneumococcal, and hepatitis A & B vaccines.
164
What are the prognosis scores for cirrhosis?
Child-Pugh score: Assesses hepatic reserve based on encephalopathy, ascites, PT, bilirubin, and albumin. MELD score: Predicts mortality using bilirubin, creatinine, INR, and age.
165
What is hepatorenal syndrome (HRS)?
Acute kidney injury in patients with advanced liver disease due to severe vasodilation and reduced renal perfusion.
166
What are the diagnostic criteria for HRS?
Oliguria. Rising serum creatinine. Low urine sodium (<10 mmol/L). No improvement with volume expansion.
167
What is the prognosis of HRS?
Poor; renal failure usually only improves with liver transplantation.
168
What is hepatopulmonary syndrome (HPS)?
A syndrome of shortness of breath and hypoxemia due to intrapulmonary vascular dilatations in patients with advanced liver disease.
169
What is orthodeoxia?
Worsening hypoxia when sitting upright (seen in severe HPS).
170
What is ascites?
The accumulation of fluid in the peritoneal cavity, most commonly due to cirrhosis and portal hypertension.
171
What are the clinical features of ascites?
Shifting dullness and fluid thrill. Tense ascites causes respiratory distress. Right-sided pleural effusion and peripheral edema may be present.
172
What are the investigations for ascites?
Ascitic fluid diagnostic aspiration: Albumin: for measurement of SAAG. Total protein. Neutrophil count: if >250 cells/mm3 : spontaneous bacterial peritonitis. Gram stain and culture for bacteria and acid-fast bacilli. Cytology for malignant cells. Amylase to exclude pancreatic ascites.
173
What is Ascitic fluid total protein used for?
May be used to differentiate causes of ascites, esp. if ascitic albumin or serum albumin is not known. Ascitic T. Protein < 25: Portal hypertension (cirrhosis) & Nephrotic syndrome. Ascitic T. Protein > 25: Heart failure.
174
What is the serum-ascitic albumin gradient (SAAG)?
SAAG >11.1 g/L (Transudate): Portal hypertension, cirrhosis, heart failure, Budd-Chiari. SAAG <11.1 g/L (Exudate): Peritoneal tuberculosis, peritoneal carcinomatosis, nephrotic syndrome, pancreatitis.
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How is ascites managed?
Sodium restriction (40 mmol/day). Diuretics: Spironolactone ± furosemide. Paracentesis: In tense ascites; albumin infusion prevents re-accumulation. TIPS: For refractory ascites. NOTE: TIPS & diuretics predispose to encephalopathy. Too rapid diuresis causes intravascular volume depletion & hypokalemia which can precipitate encephalopathy.
176
What is spontaneous bacterial peritonitis (SBP)?
Infection of ascitic fluid without an obvious source, common in cirrhotic patients.
177
What are the diagnostic criteria for SBP?
Ascitic fluid neutrophils >250 cells/mm³. Common organism: Escherichia coli.
178
How is SBP treated?
Empirical IV cefotaxime. Oral norfloxacin for secondary prophylaxis.
179
What is portal hypertension?
Increased portal vein pressure (>10 mmHg), leading to collateral circulation development.
180
What are the presenting features of portal HTN?
Gastrointestinal bleeding from esophageal or gastric (less common) varices. Ascites. Hepatic encephalopathy.
181
What are the causes of portal hypertension?
Pre-hepatic: Portal vein thrombosis. Intra-hepatic: Cirrhosis, alcoholic hepatitis, schistosomiasis. Post-hepatic: Budd-Chiari syndrome, right heart failure, IVC obstruction.
182
What are the key features of acute hepatic failure?
Rapid liver function deterioration (<2 weeks) in a previously healthy liver. Hepatic encephalopathy (confusion, asterixis, coma). Coagulopathy (INR >1.5, prolonged PT). Jaundice, hypoglycemia, cerebral edema, renal failure (hepatorenal syndrome).
183
What are the most common causes of acute hepatic failure?
Viral hepatitis: Hepatitis A, B, C, D, E. Drug toxicity: Paracetamol overdose (most common), anti-TB drugs, NSAIDs, antibiotics.
184
What is the most critical complication of acute hepatic failure?
Cerebral edema leading to brain herniation, the most common cause of death. Other complications include hypoglycemia, severe infections, renal failure, and coagulopathy.
185
What is the management of acute hepatic failure?
Supportive treatment. Emergency liver transplantation. If paracetamol overdose: N-acetylcysteine (antidote). Treatment of hepatic encephalopathy.
186
What is hepatic encephalopathy?
A neuropsychiatric syndrome caused by ammonia accumulation due to liver dysfunction.
187
What are the signs and symptoms of hepatic encephalopathy?
Confusion, forgetfulness, disorientation. Sleep disturbances (sleeping during the day, awake at night). Personality changes, irritability, mood swings. Slurred speech, poor concentration. Apathy or agitation. Asterixis (flapping tremor) of the hands. Hypertonia and hyperreflexia in severe cases. Constructional apraxia (inability to draw a simple figure like a star). Severe Cases (Grade III-IV): Coma (Grade IV). Fetor hepaticus (musty, sweet breath odor due to ammonia accumulation).
188
How is hepatic encephalopathy graded clinically?
Grade 0: No obvious symptoms but abnormal psychometric tests. Grade 1: Mild confusion, short attention span, irritability, sleep disturbances. Grade 2: Lethargy, inappropriate behavior, disoriented to time, obvious asterixis. Grade 3: Severe confusion, incomprehensible speech, marked somnolence. Grade 4: Coma, unresponsive to pain.
189
What are the precipitating factors for hepatic encephalopathy?
High protein intake. Gastrointestinal bleeding. Infection (e.g., SBP). Electrolyte imbalance, constipation, sedative drugs.
190
What investigations are done for hepatic encephalopathy?
Clinical diagnosis (rule out other causes of altered mental status). Serum ammonia: Often elevated but not always correlating with severity. EEG: Shows slow waves (δ waves) in difficult cases. Brain imaging (CT/MRI): To exclude intracranial lesions like stroke or tumor.
191
How is hepatic encephalopathy treated?
Lactulose (laxative to reduce ammonia absorption). Rifaximin/metronidazole (reduce gut bacteria that produce ammonia). Protein restriction initially, then gradual reintroduction.
192
What is the pathophysiology of A1AT deficiency?
In the liver: Abnormal A1AT accumulates in hepatocytes → liver damage and cirrhosis. In the lungs: Low A1AT leads to unopposed neutrophil elastase activity, destroying alveoli → early-onset emphysema (especially in smokers).
193
What are the genetic variants of A1AT deficiency?
Normal genotype: PiMM. Heterozygous carriers: PiMZ (mild disease risk). Severe disease genotype: PiZZ (homozygous) → Causes both liver disease and early-onset emphysema.
194
What are the clinical features of A1AT deficiency?
Early-onset COPD/emphysema, occurs before age 45, especially in non-smokers. Worse in smokers. Basal (lower lung) emphysema. Neonatal jaundice and cholestasis. Childhood cirrhosis and liver failure. Adult-onset cirrhosis and hepatocellular carcinoma (HCC). Panniculitis (painful skin nodules). Vasculitis (rare).
195
How is A1AT deficiency diagnosed?
Serum A1AT levels: Low. Genetic testing: Identifies PiZZ or PiMZ mutations. Liver biopsy: PAS-positive, diastase-resistant globules in hepatocytes. Lung function tests: Obstructive pattern with low DLCO.
196
How is A1AT deficiency treated?
Treatment is for chronic lung and liver disease. Intravenous augmentation therapy with plasma-derived A1-AT is used but not widely available. Enzyme replacement. Patients should be advised to stop smoking.
197
What is hereditary hemochromatosis?
Autosomal recessive disorder due to HFE gene mutation on chromosome 6. Leads to excessive iron deposition in organs, causing fibrosis and failure.
198
What are the common clinical features of hereditary hemochromatosis?
Often asymptomatic, diagnosed via abnormal liver biochemistry or iron studies. Organ-specific symptoms due to iron deposition: Liver: Hepatomegaly, lethargy. Pancreas: Diabetes mellitus. Heart: Cardiomyopathy, conduction disturbances. Pituitary: Loss of libido, impotence. Joints: Arthralgia (pseudogout). Skin: Hyperpigmentation ('bronze diabetes'). Increased risk of infections (Vibrio vulnificus, Yersinia, Listeria).
199
How is hereditary hemochromatosis diagnosed?
Elevated serum iron, low TIBC, high transferrin saturation (>45%). Serum ferritin >500. HFE genetic testing (PCR for C282Y mutation). MRI: Shows high iron deposition in the liver. Liver biopsy: Usually not needed unless unclear diagnosis.
200
How is hereditary hemochromatosis managed?
Phlebotomy (venesection): Remove 500 mL of blood (~250 mg iron) twice weekly until iron stores normalize. Maintenance: 3-4 venesections per year lifelong.
201
What is Wilson’s disease?
Autosomal recessive disorder due to a mutation in ATP7B gene (chromosome 13). Causes decreased copper excretion and accumulation in organs, particularly liver and brain.
202
What are the clinical features of Wilson’s disease?
Liver: Hepatitis, cirrhosis, portal hypertension, hepatic failure. Neurological: Parkinsonism, dystonia, tremors, speech difficulty, behavioral changes. Ophthalmologic: Kayser-Fleischer rings (green-brown corneal deposits). Renal: Proximal renal tubular acidosis, nephrolithiasis. Hematologic: Coombs-negative hemolytic anemia.
203
How is Wilson’s disease diagnosed?
Low serum ceruloplasmin & low serum copper. High 24-hour urinary copper excretion. High liver copper content (rhodanine stain on biopsy). Penicillamine challenge test: Causes excessive copper excretion.
204
How is Wilson’s disease treated?
Copper chelating agents: Penicillamine (avoid in penicillin allergy). Trientine (alternative chelator). Zinc therapy to reduce copper absorption. Liver transplant for end-stage liver failure. Screening of first-degree relatives.
205
What are the three major benign liver tumors?
Cavernous Hemangioma: Most common, estrogen-sensitive, risk of rupture. Focal Nodular Hyperplasia (FNH): Benign, no risk of malignancy. Kupffer cells present. Hepatocellular Adenoma: Hormone-induced, high risk of rupture and malignancy.
206
How are benign liver tumors diagnosed and managed?
Cavernous Hemangioma: Diagnosed via contrast CT/MRI, avoid biopsy, monitor unless symptomatic. FNH: No treatment required, diagnosed via contrast-enhanced CT (central scar present). Hepatocellular Adenoma: <5 cm: Monitor, stop OCP/steroids. >5 cm: Surgical resection due to risk of rupture and malignancy.
207
What are the risk factors for hepatocellular carcinoma?
HBV, HCV, cirrhosis. Aflatoxin exposure (peanuts). Hemochromatosis, α1-antitrypsin deficiency. Anabolic steroids, liver flukes.
208
How is hepatocellular carcinoma diagnosed?
Elevated α-fetoprotein (AFP). Ultrasound and contrast-enhanced CT/MRI. Guided biopsy for confirmation.
209
What are the symptoms of HCC?
Weight loss, nausea, vomiting, and jaundice, +/- splenomegaly and ascites. Dull RUQ pain & non-tender hepatomegaly in a pt with known cirrhosis.
210
What is the treatment for hepatocellular carcinoma?
Surgical resection (1 cm margin). Liver transplant (high recurrence risk). Transarterial chemoembolization (TACE), high-frequency ultrasound (HIFU) ablation.
211
What is primary sclerosing cholangitis?
Chronic fibrosing inflammation of intrahepatic and extrahepatic bile ducts. Associated with ulcerative colitis (75%). Increased risk of cholangiocarcinoma. Most common in men. Associated with HLA-A1-B8-DR3. pANCA antibodies. Symptoms include pruritus and jaundice.
212
How is PSC diagnosed?
High ALP, GGT, bilirubin. MRCP: 'Beads on a string' bile duct irregularities. Histology: Onion skin fibrosis.
213
What is the treatment for PSC?
Liver transplant (only curative option). Palliative care: Ursodeoxycholic acid, stricture dilation.
214
What is primary biliary cholangitis?
Autoimmune destruction of intrahepatic bile ducts. Common in middle-aged women, associated with autoimmune diseases (e.g., RA, Sjögren’s).
215
What are the clinical features of PBC?
Early Symptoms: Pruritus (first symptom), fatigue. Progressive Symptoms: Jaundice, hepatomegaly, pigmented xanthelasma (eyelids), xanthomas (hands, tendons). Advanced Disease: Cirrhosis, portal hypertension, osteoporosis. Unlike other cholestatic conditions, PBC is NOT associated with cardiovascular disease despite high lipid levels.
216
What are the key investigations for diagnosing PBC?
Antimitochondrial antibodies (AMA, anti-M2) positive in >95%. Other ABs: antinuclear, anti-smooth muscle antibodies. Elevated ALP & GGT (cholestatic pattern). Elevated cholesterol and IgM. Ultrasound or MRCP to rule out extrahepatic obstruction. Liver biopsy (if needed) shows portal inflammation, lymphocytic infiltration, and bile duct damage.
217
What is the treatment for PBC?
First-line: Ursodeoxycholic acid (UDCA) to slow progression. Second-line: Obeticholic acid (for patients unresponsive to UDCA). Symptomatic management: Pruritus: Cholestyramine, rifampicin, naloxone, plasmapheresis. Osteoporosis prevention: Bisphosphonates, vitamin D. Fat-soluble vitamin supplementation (A, D, E, K).
218
What are the complications of PBC?
Cirrhosis and liver failure. Portal hypertension. Osteoporosis (common). Rarely, osteomalacia and polyneuropathy.
219
What are the key pregnancy-related liver diseases?
Intrahepatic Cholestasis of Pregnancy: Pruritus (palms & soles), no rash. High bilirubin. Managed with ursodeoxycholic acid, delivery at 37 weeks. Acute Fatty Liver of Pregnancy: Jaundice, nausea, hypoglycemia, pre-eclampsia. ALT >500, requires immediate delivery. HELLP Syndrome: Hemolysis, elevated liver enzymes, low platelets, schistocytes and burr cells. Common in 3rd trimester, associated with pre-eclampsia. Manage with BP control, seizure prophylaxis, and delivery.
220
What is Budd-Chiari Syndrome?
Obstruction of venous outflow from the liver due to hepatic vein occlusion, leading to liver congestion and damage.
221
What are the causes of Budd-Chiari Syndrome?
Hypercoagulable states, oral contraceptives, leukemia, hepatic vein occlusion by tumors, trauma, radiotherapy, and hydatid cyst infections.
222
What are the clinical features of Budd-Chiari Syndrome?
Acute Form: Abdominal pain, nausea, vomiting, jaundice, ascites, tender hepatomegaly.
Chronic Form: Jaundice, caudate lobe enlargement, splenomegaly, portal hypertension, negative hepatojugular reflux.
223
How is Budd-Chiari Syndrome diagnosed?
Doppler Ultrasound (first-line).
CT/MRI if suspicion remains high.
Liver biopsy (rarely needed): Shows centrilobular congestion, necrosis, and hemorrhage.
Ascitic tap: High protein, high SAAG (>1.1 g/dL).
224
How is Budd-Chiari Syndrome managed?
Restore hepatic blood flow: Thrombolysis in acute cases, angioplasty, or stenting.
Treat ascites and any underlying condition.
TIPS or liver transplantation for fulminant hepatic failure.
225
What is acute pancreatitis?
Inflammation of the pancreas due to enzyme autodigestion caused by pancreatic duct injury.
226
What is the pathophysiology of acute pancreatitis?
Trypsin activation → Acinar cell necrosis.
Lipase & phospholipase activation → Fat necrosis.
Elastase activation → Blood vessel damage & hemorrhage.
Inflammatory response → Local & systemic effects.
227
What are the common causes of acute pancreatitis?
Mnemonic: I GET SMASHED
Idiopathic
Gallstones
Ethanol (alcohol)
Trauma
Steroids
Mumps/CMV/Coxsackie B/HSV
Autoimmune & Vasculitis
Scorpion stings/spider bites
Hyperlipidemia, hypercalcemia, hyperparathyroidism
ERCP
Drugs (Tetracyclines, Azathioprine, Furosemide, Thiazides, Estrogen, Sulfonamides)
228
What are the clinical features of acute pancreatitis?
Severe, sharp, epigastric pain radiating to the back, relieved by leaning forward.
Nausea, vomiting, fever, tachycardia, hypotension.
Hypoxia, DIC signs. Tetany.
Grey Turner’s sign: Flank bruising.
Cullen’s sign: Periumbilical bruising.
Fox’s sign: Inguinal bruising.
229
What are the CBC results in acute pancreatitis?
CBC: hemoglobin low, platelets low.
CRP: acute inflammatory marker.
Urea & electrolytes: to check renal function and refer back to it in cases imaging w/ contrast (CT, ERCP) or surgery is needed.
Liver enzymes: rule out cholelithiasis.
Prothrombin time/INR: prolonged in liver disease and DIC.
Calcium: low.
Arterial blood gas.
Amylase (3X normal) & Lipase (very specific).
Virology: mumps, CMV, coxsackie B, HSV.
230
What imaging studies are used for acute pancreatitis?
Abdominal ultrasound: First-line to check for gallstones & biliary obstruction.
CT abdomen with contrast: Best to assess severity, necrosis, and complications.
Abdominal X-ray: Sentinel loop sign: Dilated proximal bowel due to inflammation.
Colon cut-off sign: Gas-filled proximal colon ending abruptly due to pancreatic inflammation.
Exclude perforated peptic ulcer (air under diaphragm).
231
How is acute pancreatitis managed?
NPO (bowel rest), IV fluids, electrolyte correction.
NG tube (if severe vomiting).
Pain management (avoid morphine; use meperidine, tramadol).
Treat underlying cause (ERCP for gallstone pancreatitis).
232
What are the complications of acute pancreatitis?
Systemic: ARDS, DIC, renal failure.
Metabolic: Hypocalcemia, hyperglycemia.
Local: Pancreatic pseudocyst, abscess, necrosis.
233
What is chronic pancreatitis?
Persistent pancreatic inflammation causing irreversible damage, fibrosis, and pancreatic insufficiency.
234
What are the causes of chronic pancreatitis?
Mnemonic: TIGAR-O
Toxic: Alcohol, smoking, hypercalcemia, hyperlipidemia, uremia.
Idiopathic.
Genetic: CFTR, PRSS1, SPINK1 mutations.
Autoimmune.
Recurrent acute pancreatitis.
Obstructive: Tumors, ductal strictures, stones.
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What are the clinical features of chronic pancreatitis?
Epigastric pain radiating to the back (worse when lying down).
Pancreatic insufficiency: Malabsorption, steatorrhea, fat-soluble vitamin deficiencies.
Diabetes mellitus (late-stage).
Jaundice.
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What tests are used in chronic pancreatitis?
Serum amylase & lipase: May be normal or mildly elevated (unlike acute pancreatitis).
Blood glucose: Elevated due to endocrine dysfunction (diabetes mellitus).
HbA1c: Assesses long-term glucose control in suspected pancreatic diabetes.
Liver function tests (LFTs): Elevated ALP & bilirubin if biliary obstruction is present.
Calcium: May be high in hyperparathyroidism-induced pancreatitis.
Serum IgG4: Elevated in autoimmune pancreatitis.
Stool tests: Fecal elastase decreased, fecal fat test increased.
Bentiromide test (chymotrypsin activity).
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What imaging studies are used in chronic pancreatitis?
Abdominal ultrasound (CT is more sensitive): duct dilation, fluid collection, pseudocyst, irregular consistency.
Abdominal x-ray: calcification.
MRCP/ERCP: duct dilation/ stricture (chain of lakes).
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How is chronic pancreatitis managed?
Alcohol and smoking cessation.
Pancreatic enzyme replacement.
Glycemic control.
Analgesia.
ERCP: stenting narrow ducts.
Celiac plexus block for pain relief.
Resection in severe disease.
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What are the complications of chronic pancreatitis?
Pancreatic insufficiency: Malabsorption, steatorrhea, fat-soluble vitamin deficiency (A, D, E, K).
Diabetes mellitus: Due to pancreatic endocrine dysfunction.
Pancreatic pseudocyst: Fluid-filled sac, may cause pain or infection.
Biliary obstruction: Due to fibrosis or pseudocyst compressing bile ducts.
Splenic vein thrombosis: Can lead to gastric varices.
Pancreatic ascites & pleural effusion: Due to duct leakage.
Pseudoaneurysm: Rupture can cause severe bleeding.
Increased risk of pancreatic adenocarcinoma.
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What is an insulinoma?
Most common pancreatic NET; arises from β-cells, causing excessive insulin secretion and hypoglycemia. Diagnosed by Whipple’s Triad (hypoglycemia <2.8 mmol/L, symptoms of hypoglycemia, relief after glucose intake). Confirmed by high fasting insulin, high C-peptide, and insulin:glucose ratio >0.3. Treatment is surgical removal; diazoxide helps control hypoglycemia.
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What is a gastrinoma (Zollinger-Ellison Syndrome)?
A gastrin-secreting tumor leading to excess stomach acid, ulcers, and diarrhea. Found in the gastrinoma triangle (duodenum > pancreas). Secretin stimulation test shows paradoxical increase in gastrin. Associated with MEN1. Treatment is surgical resection, lifelong PPIs for symptom control, and octreotide scan for metastasis detection.
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What is a VIPoma?
A VIP-secreting tumor causing WDHA syndrome (Watery Diarrhea, Hypokalemia, Achlorhydria). Most are malignant, with early lymph node metastasis. Diagnosed by high fasting VIP levels. Treatment includes tumor resection, chemotherapy, and octreotide to reduce diarrhea.
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What is a glucagonoma?
A glucagon-secreting tumor from α-cells, leading to diabetes, weight loss, necrolytic migratory erythema (NME), DVT, and depression (4 D’s: Diabetes, Dermatitis, DVT, Depression), weight loss (low AA), mucositis and anemia. Diagnosed by high glucagon levels. Treatment is surgical resection and somatostatin analogs (octreotide).
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What is a somatostatinoma?
A rare malignant tumor secreting excess somatostatin, leading to diabetes, gallstones, steatorrhea, and hyperglycemia due to inhibition of pancreatic secretions, biliary contraction, and intestinal secretions. Diagnosed by elevated fasting somatostatin levels. Treatment includes surgical resection and chemotherapy.
