GI Flashcards
(194 cards)
1
Q
Name function of gastrin and source
A
Produced by G cells of the antrum of stomach + duodenum
Role = increased H+ secretion in the stomach, proliferation of the gastric mucosa and increased gastric motility
2
Q
What increases vs decreases gastrin production
A
Increased by stomach distenstion/alkalinization, amino acids, peptides, vagal stimulation via gastrin-releasing peptide
Decreased by a pH < 1.5 in the stomach
3
Q
Effect of chronic PPI on gastrin production
A
Increased
4
Q
Effect of H pylori chronic atrophic gastritis on gastrin production
A
Increased
5
Q
What is Zollinger-Ellison syndrome?
A
Endocrine disorder = mutation of the G cells in the pancreas and duodenum. Can be benign or malignant.
3 pathologies: gastrinoma (gastrin-secreting tumor) = increased gastric acid secretion from parietal cells = peptic ulcers, which causes most of the symptoms
6
Q
Stomach vs duodenal ulcer pain in relation to eating
A
Stomach ulcer pain increases with eating due to acid secretions
Duodenal ulcer pain decreases with eating thanks closed pyloric sphincter
7
Q
What is ghrelin and when is it secreted?
A
Appetite hormone
Increased in fasting, decreased by food
8
Q
What happens to ghrelin in Prader-Willi syndrome?
A
Increased during infancy = obese patients
9
Q
What is Somatostatin, where is it secreted, what are its functions?
A
Secreted by D cells of pancreatic islets and GI mucosa
Decreases gastric acid and pepsinogen secretion
Decreases pancreatic and small intestine fluid secretion
Decreases gallbladder contraction
Decreases insulin and glucagon release
10
Q
What are physiological triggers and inhibitors of somatostatin release?
A
Triggers = increased acid
Inhibitors = vagal stimulation
10
Q
What is the name of a somatostatin analogue what in which diseases is it used as a treatment?
A
Octreotide: acromegaly, carcinoid syndrome, VIPoma, variceal bleeding
11
Q
What is CCK, where is it released and what are its functions?
A
Cholecystokinin
I cells of the duodenum and jejunum
Increases pancreatic secretion (neural muscarinic pathways)
Increases gallbladder contraction
Decreases gastric emptying
Increases sphincter of Oddi relaxation
12
Q
Physiologic triggers of CCK release
A
Fatty acids and amino acids
13
Q
What is secretin, where is it secreted and what are its roles?
A
S cells of the duodenum
Increases pancreatic HCO3- secretion
Decreases acid secretion
Increases bile secretion
Goal = neutralize gastric acid in the duodenum, allowing pancreatic enzymes to function
14
Q
What is a physiologic trigger of secretin production
A
Acid and fatty acids in the lumen of the duodenum
15
Q
What is glucose-dependent insulinotropic peptide?
A
AKA gastric inhibitory peptide (GIP)
Produced by K cells of duodenum and jejunum
Triggers insulin release (endocrine) and decreased gastric H+ release (exocrine) in response to fatty acids, amino acids and oral glucose.
16
Q
Motilin - what is it, where is it secreted and what triggers it?
A
Substance producing migrating motor complexes (MMCs), released in a fasting state at the small intestine
17
Q
What is vasoactive intestinal peptide, where is it secreted and what are its functions?
A
Parasympathetic ganglia in sphincters, gallbladder and small intestine.
VIP is a neurotransmitter and hormone found in the gut, pancreas, and brain. It causes relaxation of smooth muscle, dilation of blood vessels, decreased acid secretion in the stomach and stimulation of intestinal secretion (like water and electrolytes (Cl-) into the intestines).
18
Q
What increases vs decreases VIP release?
A
Increased by distention and vagal stimulation (parasympathetic NS)
Decreased by adrenergic input (sympathetic NS)
19
Q
Symptoms of VIPoma
A
A VIPoma is a rare neuroendocrine tumor (usually of the pancreas) that secretes excess vasoactive intestinal peptide (VIP). Too much VIP causes:
* Profuse watery diarrhea
* Hypokalemia (low potassium)
* Achlorhydria (reduced stomach acid)
This is known as WDHA syndrome (Watery Diarrhea, Hypokalemia, Achlorhydria), also called Verner-Morrison syndrome.
20
Q
Management of VIPoma
A
Somatostatin analogues (Octreotide), which decrease VIP secretion
21
Q
Role of NO in the GI tract
A
Increased smooth muscle relaxation, including of the lower esophageal sphincter
22
Q
Two substances secreted by parietal cells of the stomach
A
Gastric acid
Intrinsic factor
23
Q
2 types of cells secreting bicarbonate
A
Mucosal cells (stomach, duodenum, salivary glands, pancreas)
Brunner cells (duodenum)
24
Which gastric secretory product is responsible for lowering stomach pH, and what stimulates its release?
Gastric acid, secreted by parietal cells, lowers stomach pH. Its release is stimulated by histamine, vagal stimulation (via ACh), and gastrin.
25
What is the function of intrinsic factor and what condition can result from its deficiency?
Intrinsic factor binds vitamin B₁₂ to enable its absorption in the terminal ileum. Deficiency can lead to pernicious anemia.
26
What inhibits gastric acid secretion, and what autoimmune condition is associated with parietal cell destruction?
Gastric acid secretion is inhibited by somatostatin, GIP, prostaglandins, and secretin.
Autoimmune destruction of parietal cells causes chronic gastritis and pernicious anemia.
27
What are the two main types of chronic gastritis and how do they differ?
Type A (Autoimmune): Affects the fundus and body, caused by autoimmune destruction of parietal cells, leading to pernicious anemia and achlorhydria.
Type B (Bacterial): Affects the antrum, caused by H. pylori infection, associated with peptic ulcers and increased risk of gastric cancer.
28
Which cells secrete pepsinogen in the stomach?
Chief cells of the stomach secrete pepsinogen, the inactive precursor of pepsin.
29
What activates pepsinogen into its active form, pepsin?
Pepsinogen is activated to pepsin in the presence of hydrogen ions (H⁺), i.e., in an acidic environment.
30
What is the primary function of pepsin in digestion?
Pepsin is a protease that helps in the digestion of proteins in the stomach.
31
What stimulates the release of pepsinogen from chief cells?
Vagal stimulation (via acetylcholine, ACh) and local gastric acid stimulate pepsinogen release.
32
What hormone stimulates increased pancreatic and biliary secretion of bicarbonate?
Secretin stimulates the pancreas and biliary system to release more bicarbonate.
33
How does gastrin increase gastric acid secretion, and which cells does it act on?
Gastrin increases acid secretion indirectly by stimulating ECL cells to release histamine, which then acts on parietal cells to increase HCl production.
34
What is the difference between H₁ and H₂ histamine blockers, and what are they used for?
H₁ blockers: Treat allergies by blocking histamine at H₁ receptors in the skin, nose, and airways.
H₂ blockers: Reduce stomach acid by blocking histamine at H₂ receptors on parietal cells in the stomach.
35
What type of fluid do pancreatic secretions produce, and how does flow rate affect its composition?
Pancreatic secretions are isotonic.
* Low flow: High Cl⁻
* High flow: High HCO₃⁻
36
What enzyme is responsible for starch digestion in the pancreas?
α-amylase, which is secreted in its active form.
37
What enzymes digest lipids in the pancreas?
Lipases, which are secreted in their active form.
38
What is the role of pancreatic proteases?
Protein digestion, involving enzymes like trypsin, chymotrypsin, elastase, and carboxypeptidase.
39
How are pancreatic proteases initially secreted?
As inactive proenzymes (zymogens).
40
How are dietary proteins digested and absorbed in the small intestine?
Pancreatic proteases (like trypsin, chymotrypsin) are secreted as inactive zymogens and activated in the small intestine.
These enzymes break proteins down into dipeptides, tripeptides, and some free amino acids in the intestinal lumen.
Dipeptides and tripeptides are then absorbed by enterocytes and further degraded by intracellular peptidases into individual amino acids, which are transported into the bloodstream.
41
What is the role of enterokinase/enteropeptidase?
It converts trypsinogen to trypsin, initiating the activation cascade of digestive enzymes.
42
How does trypsin contribute to a positive feedback loop?
Trypsin activates other proenzymes and additional trypsinogen molecules.
43
What hormone stimulates acinar cell enzyme secretion and through which receptor?
Cholecystokinin (CCK) via the CCK-1 receptor on acinar cells.
44
How are glucose and galactose absorbed in the small intestine?
They are absorbed by SGLT-1, a sodium-dependent transporter on the apical membrane of enterocytes.
45
How is fructose absorbed in the small intestine?
Fructose is absorbed via facilitated diffusion through GLUT-5 on the apical membrane.
46
Which transporter moves all monosaccharides from the enterocyte into the blood?
GLUT-2, located on the basolateral membrane of enterocytes.
47
Only _____________ (a form of sugar) are absorbed my enterocytes
Monosaccharides
48
How is vitamin B₁₂ absorbed in the gastrointestinal tract?
* In the stomach, B₁₂ binds R-binders.
* In the duodenum, R-binders are degraded and B₁₂ binds intrinsic factor (IF).
* In the terminal ileum, the B₁₂–IF complex is absorbed.
* B₁₂ then binds transcobalamin II for transport in the blood.
49
Other name for Vitamin B12
cobalamine
50
What are the common causes and symptoms of vitamin B₁₂ deficiency?
Causes:
* Pernicious anemia (↓ intrinsic factor), gastric surgery, ileal disease (e.g., Crohn’s), pancreatic insufficiency (inadequate digestion of R-binders), vegan diet (no intake)
Symptoms:
* Megaloblastic anemia, glossitis, and neurologic symptoms like paresthesias, gait issues, and subacute combined degeneration.
51
What is Barrett esophagus, and what causes it?
Barrett esophagus is the replacement of nonkeratinized stratified squamous epithelium in the distal esophagus with intestinal epithelium (nonciliated columnar with goblet cells). It is caused by chronic GERD (gastroesophageal reflux disease).
52
What is the clinical significance of Barrett esophagus?
It is a form of intestinal metaplasia and is associated with an increased risk of esophageal adenocarcinoma.
53
What is celiac disease and what genetic markers is it associated with?
Celiac disease is an autoimmune intolerance to gliadin (a gluten protein) that causes malabsorption and steatorrhea. It is associated with HLA-DQ2 and HLA-DQ8.
54
What are the key histological findings in celiac disease?
Histology shows villous atrophy, crypt hyperplasia, intraepithelial lymphocytosis, and mucosal atrophy
55
What serologic tests are used to diagnose celiac disease?
Positive IgA anti-tissue transglutaminase (tTG)
56
What clinical features and complications are associated with celiac disease?
Dermatitis herpetiformis
* Iron deficiency anemia
* ↓ Bone density (due to malabsorption)
* Increased risk of T-cell lymphoma
* Positive D-xylose test (abnormal with mucosal damage)
57
What causes lactose intolerance and what are its key features?
Lactose intolerance is due to lactase deficiency, leading to osmotic diarrhea and ↓ stool pH. Villi are usually normal unless injured (e.g., viral enteritis).
58
What test is used to diagnose lactose intolerance, and what result indicates malabsorption?
The lactose hydrogen breath test is used; a rise > 20 ppm in hydrogen from baseline indicates positive lactose malabsorption.
59
What are the causes and consequences of pancreatic insufficiency?
Causes include chronic pancreatitis, cystic fibrosis, and obstructing cancer. It leads to malabsorption of fats and fat-soluble vitamins (A, D, E, K) as well as vitamin B₁₂; D-xylose test is normal.
60
What part of the GI tract is affected in Crohn disease versus ulcerative colitis?
Crohn can affect any part, especially the terminal ileum and colon (with skip lesions); UC affects only the colon, with continuous lesions starting at the rectum.
61
What region of the bowel wall has inflammation in Crohn disease versus ulcerative colitis?
Crohn has transmural inflammation; UC has mucosal and submucosal inflammation only.
62
How do the microscopic (histological) findings differ between Crohn disease and ulcerative colitis?
* Crohn disease shows noncaseating granulomas and lymphoid aggregates.
* Ulcerative colitis shows crypt abscesses, mucosal ulceration, and no granulomas.
63
Compare these complications in Chron's vs ulcerative colitis
PSC = primary sclerosing cholangitis
64
Why do patients with Crohn disease have an increased risk of calcium oxalate kidney stones?
Fat malabsorption causes calcium to bind unabsorbed fats instead of oxalate. This leads to increased oxalate absorption, which is then excreted by the kidneys and forms calcium oxalate stones.
65
What extraintestinal manifestations are shared by both Crohn and UC?
Rash (pyoderma gangrenosum, erythema nodosum), arthritis, eye inflammation, and oral ulcers.
66
How are Crohn disease and ulcerative colitis treated?
* Crohn: Steroids, immunomodulators, antibiotics (e.g., ciprofloxacin), biologics (e.g., infliximab).
* UC: 5-ASA (e.g., mesalamine), immunosuppressants, biologics, and colectomy is curative.
67
Diarrhea bloodiness in Chron's vs UC
Chron's: may or may not be bloody
UC: always bloody
68
What is fecal calprotectin, and what does an elevated level indicate?
Fecal calprotectin is a marker of intestinal inflammation derived from neutrophils. Elevated levels suggest inflammatory bowel disease (IBD) such as Crohn disease or ulcerative colitis, and help differentiate IBD from non-inflammatory conditions like irritable bowel syndrome (IBS).
69
What imaging sign is characteristic of Crohn disease?
The “string sign” on barium swallow, representing a narrowed terminal ileum due to transmural inflammation and stricture formation.
70
What imaging sign is characteristic of ulcerative colitis?
The “lead pipe” appearance on imaging, reflecting loss of haustra due to chronic mucosal inflammation and fibrosis.
71
What is a diverticulum and how does it differ between true and false types?
A diverticulum is a blind pouch protruding from the GI tract wall that communicates with the lumen.
* True diverticulum: includes all layers of the wall (e.g., Meckel).
* False (pseudo) diverticulum: includes only mucosa and submucosa (e.g., Zenker).
72
What is diverticulosis, and where is it most commonly found?
Diverticulosis is the presence of many false diverticula, especially in the sigmoid colon. It’s common in older adults (>60 years).
73
What causes diverticulosis?
It’s caused by increased intraluminal pressure and focal weakness in the colon wall. Risk factors include low-fiber, high-fat diets, and obesity.
74
What are the common symptoms and complications of diverticulosis?
Often asymptomatic or causes vague discomfort. Complications include painless hematochezia and diverticulitis.
75
What is diverticulitis and how does it present clinically?
Diverticulitis is inflammation of diverticula with wall thickening, typically presenting with LLQ pain, fever, and leukocytosis.
76
How is diverticulitis managed?
Uncomplicated: supportive care
* Complicated (abscess, perforation): antibiotics
77
What are the complications of diverticulitis?
Abscess, fistula (e.g., colovesical → pneumaturia), obstruction, perforation → peritonitis. Hematochezia is rare.
78
What imaging findings are associated with diverticulitis?
CT scan shows wall thickening, pericolic fat stranding, and possibly air or fluid collections. Red and white arrows may indicate inflammation and perforation, respectively.
79
What is the H. pylori infection rate in gastric vs. duodenal ulcers?
*Gastric ulcers: ~70% associated with H. pylori
* Duodenal ulcers: ~90% associated with H. pylori
80
How does cancer risk differ between gastric and duodenal ulcers?
* Gastric ulcers have increased cancer risk → biopsy recommended
* Duodenal ulcers are generally benign → not routinely biopsied
81
What is a Zenker diverticulum and where does it occur?
A pharyngoesophageal false diverticulum caused by esophageal dysmotility and herniation through Killian’s triangle, between the thyropharyngeus and cricopharyngeus muscles.
82
What symptoms are associated with Zenker diverticulum?
Dysphagia, obstruction, gurgling, aspiration, foul breath, and a neck mass. Most common in older males.
83
Where does a Meckel diverticulum arise, and what is its embryologic origin?
Meckel diverticulum arises from the antimesenteric border of the ileum, about 2 feet from the ileocecal valve. It results from persistent vitelline (omphalomesenteric) duct.
84
What is a Meckel diverticulum, and what causes it?
A true diverticulum caused by the persistence of the vitelline duct. It may contain ectopic gastric or pancreatic tissue and is the most common congenital GI anomaly.
85
What are the clinical signs and complications of Meckel diverticulum?
Can cause painless hematochezia, melena, RLQ pain, intussusception, volvulus, or obstruction near the terminal ileum.
86
What is the “rule of 2s” for Meckel diverticulum?
* Occurs in 2% of the population
* 2 inches long
* 2 feet from ileocecal valve
* 2 types of ectopic tissue (gastric, pancreatic)
* Presents by age 2
* 2x more common in males
87
What causes Hirschsprung disease and what genetic mutation is it associated with?
It is caused by failure of neural crest cell migration, leading to absence of Auerbach and Meissner plexuses in the distal colon. It is associated with loss-of-function mutations in the RET gene.
88
What are the clinical features of Hirschsprung disease in a newborn?
Presents with bilious vomiting, abdominal distention, failure to pass meconium within 48 hours, and chronic constipation. On digital rectal exam: explosive expulsion of stool (squirt sign).
89
How is Hirschsprung disease diagnosed and treated?
Diagnosed by absence of ganglion cells on rectal suction biopsy. Treatment is surgical resection of the aganglionic segment.
90
What is intestinal malrotation and what serious complication can it lead to?
Malrotation is an anomaly of midgut rotation during development → abnormal bowel positioning and fibrous (Ladd) bands → risk of volvulus and duodenal obstruction.
91
What is intussusception and what are its hallmark signs in children?
92
What is volvulus and what are the two most common types by age?
Volvulus is twisting of bowel around its mesentery, leading to obstruction or infarction.
* Midgut volvulus: more common in infants/children
* Sigmoid volvulus: more common in older adults
93
Which two conditions related to physical obstruction are most likely to present with visible blood in stool in infants, and how do they differ?
* Intussusception: Painful currant jelly stools
* Meckel’s diverticulum: Painless hematochezia
94
Two kinds of polyps potentially malignant
Adenomatous (villous > tubular)
Serrated
95
What is Lynch syndrome, what causes it, and what cancers are associated with it?
Lynch syndrome (HNPCC) is an autosomal dominant disorder caused by germline mutations in DNA mismatch repair (MMR) genesleading to microsatellite instability.
It increases the risk of colorectal cancer (especially right-sided), endometrial cancer, and others including ovarian and skin cancers.
96
Biopsy of which area of the GI tract to confirm Celiac?
Duodenum and proximal jejunum since there are the highest concentrations of gliadin. there.
97
What causes diabetic gastroparesis and how is it diagnosed?
Caused by autonomic neuropathy and enteric neuron destruction, leading to poor gastric motility. Diagnosed with a nuclear gastric emptying study showing delayed gastric transit into the duodenum.
98
What are the key symptoms and treatment of diabetic gastroparesis?
Symptoms include postprandial bloating, vomiting, early satiety, and weight loss. Treated with promotility drugs like metoclopramide and erythromycin.
99
What are the key clinical features and causative organism of Whipple disease?
Whipple disease is caused by Tropheryma whipplei and typically presents in middle-aged men with malabsorption (steatorrhea, weight loss), abdominal pain, diarrhea, arthralgia, and sometimes CNS symptoms like dementia.
100
How is Whipple disease diagnosed and treated?
Diagnosis is confirmed by small intestine biopsy showing foamy macrophages with T. whipplei bacilli, which are PAS-positive. Treatment involves long-term (≥12 months) antibiotic therapy.
101
How do proton pump inhibitors (PPIs) improve fat absorption in patients with pancreatic insufficiency?
PPIs reduce stomach acidity, preventing the inactivation of exogenous lipase. This increases lipase activity, enhancing fat absorption during pancreatic enzyme replacement therapy.
102
What causes gastric MALT lymphoma and how does Helicobacter pylori contribute to its development?
Chronic immune stimulation from H. pylori infection recruits antigen-specific lymphocytes. Over time, this leads to the emergence of a monoclonal B-cell population that can grow independently of the original antigen stimulus.
103
How can early-stage gastric MALT lymphoma be treated and potentially cured?
Since it is often driven by H. pylori, antimicrobial treatment can lead to complete remission by eliminating the antigenic trigger for tumor proliferation.
104
What is a histological hallmark of chron's disease
non-caseating granulomas
105
Is the lower esophageal sphincter (LES) normally open or closed at rest, and what maintains this state?
The LES is normally closed at rest, maintained by myogenic tone and excitatory cholinergic input (acetylcholine via the vagus nerve), preventing reflux.
106
What mediates physiological relaxation of the LES during swallowing?
LES relaxation is mediated by inhibitory neurons releasing nitric oxide (NO) and vasoactive intestinal peptide (VIP), allowing passage of food into the stomach.
107
Effective treatment for achalasia (increased LES tone)
Botulinum toxin
108
What clinical features suggest Zollinger-Ellison syndrome, and what key finding helps distinguish it from other causes of ulcers?
ZES presents with distal duodenal ulcers, diarrhea, and high or rising gastrin levels after secretin administration. Ulcers beyond the duodenal bulb suggest ZES over H. pylori or NSAID-induced ulcers.
109
What are the key features of a congenital umbilical hernia?
It results from incomplete closure of the umbilical ring and presents as a benign, reducible, midline protrusion covered by skin.
110
How does an omphalocele present, and what is its pathophysiology?
Caused by failed physiologic gut reduction, omphaloceles appear as a midline sac containing bowel ± organs, covered only by peritoneum.
111
What distinguishes gastroschisis from other abdominal wall defects?
It is a full-thickness defect with eviscerated bowel not covered by any membrane, located to the right of the umbilicus.
112
How does Helicobacter pylori infection lead to duodenal vs gastric ulcers?
* Duodenal ulcers: Caused by H. pylori infection in the antrum, which depletes somatostatin (delta cells) → ↑ gastrin → ↑ acid → acid injury to duodenum.
* Gastric ulcers: Caused by infection in the corpus, leading to atrophic gastritis and ↓ parietal cells → impaired mucosal defense → direct mucosal damage.
113
What are the physiologic reasons for benign neonatal hyperbilirubinemia?
1. Increased bilirubin production from rapid breakdown of fetal RBCs (shorter lifespan, higher hematocrit).
2. Decreased conjugation due to low UDP-glucuronosyltransferase activity in the immature liver.
3. Increased enterohepatic circulation from low gut flora and high β-glucuronidase activity, leading to bilirubin reabsorption.x
114
Risk factors for hypertrophic pyloric stenosis, clinical presentation
115
Why can patients experience heartburn upon cessation of long-term use of proton pump inhibitors (PPIs)?
Chronic PPI use (>8 weeks) inhibits acid production, causing increased gastric pH, which stimulates gastrin release. Elevated gastrin levels lead to hypertrophy of enterochromaffin-like (ECL) and parietal cells. Upon abrupt cessation of PPIs, these hyperfunctioning cells cause rebound gastric acid hypersecretion, leading to heartburn and reflux symptoms.
Gradual tapering of PPIs can prevent this effect.
116
How does cholestasis lead to fat and vitamin malabsorption?
Cholestasis reduces bile flow due to hepatocellular dysfunction or biliary obstruction. Without adequate bile salts, fat digestion is impaired, leading to malabsorption of fats and fat-soluble vitamins (A, D, E, and K), which require bile for absorption.
117
What is midgut malrotation, and what complications can it cause in newborns?
Midgut malrotation results from incomplete intestinal rotation, causing the duodenojejunal flexure and cecum to lie abnormally in the right upper quadrant. Ladd bands may compress the duodenum, leading to intestinal obstruction, bilious vomiting, and abdominal distension.
It also creates a narrow mesenteric base, predisposing to midgut volvulus, which can twist around the superior mesenteric artery, risking bowel ischemia and necrosis.
118
What are the typical liver function test (LFT) findings in a patient with acute viral hepatitis?
Significant elevations in ALT and AST, with ALT greater than AST, followed by rises in bilirubin.
119
What are the typical liver function test (LFT) findings in alcohol-induced hepatitis?
AST:ALT ratio greater than 2:1, often in the context of a significant alcohol use history.
120
What is the underlying pathophysiology of a congenital umbilical hernia?
ncomplete closure of the umbilical ring (fascial opening), allowing abdominal contents to protrude through the abdominal wall.
121
What are the clinical and laboratory features of acute cholangitis? (triad and pentad)
* Clinical (Charcot triad): Fever, right upper quadrant (RUQ) pain, jaundice
* Severe cases (Reynolds pentad): + Hypotension and altered mental status
* Lab findings: Leukocytosis, direct hyperbilirubinemia, and elevated alkaline phosphatase
122
Which liver markers are elevated in hepatocellular vs. cholestatic injury patterns, and what do they indicate?
* Hepatocellular injury: ↑ ALT and AST → indicates liver cell (hepatocyte) damage, as seen in autoimmune hepatitis or viral hepatitis.
* Cholestatic injury: ↑ ALP and GGT → indicates bile duct injury or obstruction, as seen in PBC and PSC.
* Bilirubin may rise in both, especially if bile flow is impaired. (cholestatic)
123
What is the “Rule of 2s” in Meckel’s diverticulum?
* Often presents by age 2
* Usually <2 inches long
* Located within 2 feet of the ileocecal valve
124
What type of ectopic tissue is most commonly found in a Meckel’s diverticulum, and what complication can it cause?
* The most common ectopic tissue is gastric mucosa.
* It secretes hydrochloric acid, which can lead to ulceration and erosion of adjacent intestinal mucosa, potentially causing bleeding.
125
How does CFTR dysfunction lead to the main features of cystic fibrosis?
Impaired CFTR function reduces water content in secretions, leading to thick, viscous mucus that causes chronic airway obstruction and gastrointestinal malabsorption.
126
What are the respiratory manifestations of cystic fibrosis?
Chronic, productive cough and recurrent sinopulmonary infections, especially with Staphylococcus aureus, Pseudomonas aeruginosa, and Burkholderia cepacia complex.
127
What gastrointestinal issue is common in cystic fibrosis?
Pancreatic insufficiency, leading to malabsorption and failure to thrive.
128
What is a common reproductive complication of cystic fibrosis in males?
Male infertility due to bilateral absence of the vas deferens.
129
What is the most commonly used test to diagnose cystic fibrosis?
Elevated sweat chloride levels via the sweat test.
130
What is the rapid urease test, how does it work, and what does a positive result indicate?
The rapid urease test is an indirect diagnostic tool used to detect Helicobacter pylori infection, a common cause of peptic ulcers.
* Mechanism:
H. pylori produces the enzyme urease, which catalyzes the reaction:
Urea → Ammonia (NH₃) + Carbon dioxide (CO₂)
* This raises the local pH (alkaline shift).
A pink color change is positive, confirming active H. pylori infection.
This test is quicker than culturing and useful during endoscopy.
131
What causes pancreatic insufficiency in cystic fibrosis, and what are its consequences?
In CF, viscous mucus obstructs and distends the pancreatic ducts, leading to inflammation and fibrosis in utero. This results in pancreatic insufficiency (PI), present from birth in most CF patients.
Consequences include:
* Inability to absorb fats and fat-soluble vitamins (A, D, E, K)
* Steatorrhea (fatty stools)
* Failure to thrive
* Patients require pancreatic enzyme supplementation for treatment.
132
What is this AXR suggestive of in the context of 3 month old with abdo distension
133
What is acalculous cholecystitis, and in which patients does it most commonly occur?
Acalculous cholecystitis is acute inflammation of the gallbladder without gallstones, typically seen in critically ill patients (e.g., sepsis, burns, trauma, immunosuppression).
It is associated with gallbladder stasis and ischemia, leading to wall inflammation and injury.
134
What are the clinical features and diagnostic findings in acalculous cholecystitis?
* Clinical signs: Fever, right upper quadrant pain, positive Murphy’s sign, leukocytosis, mild LFT elevation, jaundice, RUQ mass.
* Often subtle in sedated or intubated patients.
* Ultrasound is the test of choice: shows an enlarged, edematous gallbladder without gallstones.
135
What are the hallmark features and diagnostic markers of dermatomyositis?
Dermatomyositis presents with proximal muscle weakness and heliotrope rash (e.g., on eyelids). It affects striated muscle and skin.
Key diagnostic markers include:
* ↑ Muscle enzymes (e.g., creatine kinase)
* Positive ANA (high sensitivity) and anti-Jo-1 (high specificity)
136
What complications can arise from dermatomyositis affecting other striated muscles?
* Dysphagia and risk of aspiration (involvement of oropharynx and upper esophagus)
* Interstitial lung disease
* Myocarditis (due to striated cardiac muscle involvement)
137
What are the causes and characteristics of black pigment gallstones?
Black pigment stones are associated with chronic hemolysis (e.g., sickle cell disease, spherocytosis) and increased enterohepatic cycling of bilirubin (e.g., ileal disease). These conditions raise unconjugated bilirubin levels, leading to calcium-bilirubinate precipitation in the gallbladder.
138
What is the pathogenesis of brown pigment gallstones?
Brown pigment stones form due to biliary tract infections (e.g., E. coli, liver fluke), which release microbial β-glucuronidases. These enzymes increase unconjugated bilirubin, causing calcium-bilirubinate precipitation, typically in the bile ducts.
139
WHich part of the brain is affected by bilirubin-induced-neurologic-dysfunction (BIND)?
The basal ganglia
140
How do the endoscopic findings of HIV-associated esophagitis differ between Candida albicans, HSV-1, and CMV?
* Candida albicans: Patches of adherent gray/white pseudomembranes on erythematous mucosa.
* HSV-1: Small vesicles that evolve into “punched-out” ulcers.
* CMV: Linear ulcerations along the esophagus.
141
What is the pathogenesis of hepatic fibrosis in cirrhosis?
Chronic inflammation and oxidative stress activate stellate (Ito) cells in the space of Disse. These cells transform into myofibroblasts, which proliferate, attract other cells (chemotaxis), and produce collagen, forming thick collagenous bands that separate hepatocyte clusters, leading to progressive scar formation and cirrhosis.
142
What is the difference between anti-HAV IgM and IgG, and what do they indicate?
* Anti-HAV IgM: Indicates acute or recent hepatitis A virus (HAV) infection; usually detectable during the first weeks of illness.
* Anti-HAV IgG: Indicates past infection or immunity (either from previous infection or vaccination); persists for life and provides long-term protection.
143
How do histological and clinical findings differ between autoimmune hepatitis (AIH) and acetaminophen overdose?
* AIH: Characterized by lymphoplasmacytic infiltrates in the liver; typically presents more chronically.
* Acetaminophen overdose: Causes hepatic necrosis with neutrophilic infiltration; presents acutely with vomiting, diaphoresis, and confusion.
144
Which liver zones are affected first in viral hepatitis vs. ischemic or toxic injury, and why?
* Viral hepatitis primarily affects Zone 1 (periportal zone) first, as this area is closest to incoming blood from the portal vein, allowing early immune cell and virus interaction.
* Ischemia and metabolic toxins affect Zone 3 (pericentral zone) first because it is farthest from oxygenated blood and has high cytochrome P450 activity, increasing susceptibility to hypoxia and toxins.
145
What liver enzyme pattern is typically seen in viral hepatitis vs alcoholic hepatitis and why?
In viral hepatitis, ALT > AST because ALT (alanine aminotransferase) is more specific to hepatocytes and is released in greater amounts during liver cell injury caused by viral infection. This pattern helps distinguish viral hepatitis from alcoholic liver disease, where AST > ALT.
146
What is the prognosis of hepatitis A (HAV) infection?
HAV infection is self-limiting, does not progress to chronic hepatitis, and carries no risk of cirrhosis or hepatocellular carcinoma. The prognosis is good.
147
What is the serologic marker of an acute HAV infection?
Anti-HAV IgM is present during active infection and indicates recent or acute hepatitis A.
148
What does the presence of Anti-HAV IgG indicate?
Anti-HAV IgG indicates prior infection or vaccination, and it confers long-term immunity. Hepatitis A has no carrier state.
149
How is Hepatitis E (HEV) transmitted, and what is its prognosis?
HEV is transmitted via the fecal-oral route, typically through undercooked seafood or contaminated water, and is linked to waterborne epidemics. It has a short incubation period and does not progress to chronic hepatitis, with no risk of hepatocellular carcinoma.
150
What serious complication can Hepatitis E cause in pregnancy?
HEV infection can lead to fulminant hepatitis in pregnant women, resulting in severe liver impairment and potentially life-threatening outcomes.
151
Are there treatments / vaccines for HEV?
No; supportive treatment.
152
What are the modes of transmission of Hepatitis B virus (HBV)?
Horizontal: Parenteral – via blood exposure (e.g., IV drug use, needle sticks, dialysis, transfusions); Sexual – through semen, vaginal fluids.
Vertical: from mother to child via placenta, or exposure to blood, body fluids, or breastmilk during or after birth.
153
What are the odds of Hepatitis B (HBV) progressing to chronic hepatitis based on age, and how are babies born to HBV-positive mothers managed?
* Adults: ~5% risk of chronic hepatitis
* Children: 20–30% risk
* Infants: ~90% risk
Management of exposed newborns:
* Immediate administration of anti-HBV immunoglobulin
* First dose of HBV vaccine at birth to prevent chronic infection
154
What do the following Hepatitis B serologic markers indicate?
* HBsAg
* Anti-HBs
* HBcAg
* Anti-HBc IgM vs. IgG
* HBsAg: Active HBV infection
* Anti-HBs: Recovery or immunity (via infection or vaccination)
* HBcAg: Active viral replication (not usually measured in serum)
* Anti-HBc IgM: Recent infection (< 6 months)
* Anti-HBc IgG: Past resolved or chronic infection
155
In the natural course of Hepatitis B infection, which viral marker disappears first: HBeAg or HBsAg?
HBeAg disappears first, indicating reduced viral replication. HBsAg disappears later, marking recovery from infection. Persistence of HBsAg beyond 6 months indicates chronic infection.
156
What are the key features of Hepatitis D virus (HDV)?
* Single-stranded RNA virus
* Parenterally transmitted
* Requires HBsAg from Hepatitis B virus to infect hepatocytes
* Occurs as:
* Co-infection: HBV and HDV acquired simultaneously
* Superinfection: HDV infects someone with chronic HBV → worse prognosis, higher risk of cirrhosis
157
Why does the host immune system have difficulty mounting an effective response to Hepatitis C virus (HCV)?
HCV lacks 3′→5′ exonuclease activity, so it cannot correct replication errors. This leads to frequent mutations and high variability in antigenic structure, making it hard for the immune system to recognize and clear the virus. As a result, chronic infection is common.
158
Extrahepatic manifestations of HCV
159
How does altered enterohepatic circulation contribute to gallstone formation?
In conditions like Crohn disease or ileal resection, bile acids are not reabsorbed in the ileum and spill into the colon. There, they solubilize unconjugated bilirubin, promoting its reabsorption and concentration in bile, which can lead to bilirubin stone (pigment stone) formation.
160
What is biliary sludge, how does it form, and what are its clinical implications?
Biliary sludge is a viscous mixture of cholesterol crystals, calcium bilirubinate, mucin, and other calcium salts that forms due to gallbladder hypomotility. Inadequate emptying dehydrates bile, promoting precipitation of these particles. It may be asymptomatic or cause biliary colic, and is a precursor to gallstones.
Risk factors: pregnancy, rapid weight loss, spinal cord injury, prolonged parenteral nutrition, or octreotide use.
161
How does chronic Hepatitis B virus (HBV) infection assist the life cycle of Hepatitis D virus (HDV)?
Chronic HBV provides HBsAg (Hepatitis B surface antigen), which HDV requires to coat its viral particles. This coating is essential for HDV to enter hepatocytes and propagate, making HBV infection a prerequisite for HDV replication and spread.
162
What is the function of alpha-1 antitrypsin and what happens in its deficiency?
Alpha-1 antitrypsin is a protease inhibitor that protects tissues by inhibiting neutrophil elastase. In AATD, unchecked elastase activity leads to alveolar destruction and panacinar emphysema, especially in the lower lung lobes.
163
How does alpha-1 antitrypsin deficiency lead to liver disease?
In AATD, misfolded alpha-1 antitrypsin proteins accumulate in hepatocytes, causing cellular damage. This can lead to hepatomegaly, elevated transaminases, cirrhosis, and increased risk of hepatocellular carcinoma.
164
What causes Reye syndrome and in whom does it typically occur?
Reye syndrome occurs in children given aspirin during a viral illness (e.g., influenza, varicella). It results from mitochondrial toxicity and impaired fatty acid metabolism.
165
What is the hepatic pathology in Reye syndrome?
Hepatic dysfunction leads to hepatomegaly, elevated transaminases, and hyperammonemia, with microvesicular steatosis seen on liver biopsy. Jaundice is rare.
166
What is the pathogenesis of Wilson disease?
Wilson disease is caused by an autosomal recessive mutation in the ATP7B gene, leading to hepatic copper accumulation. Damaged hepatocytes release copper, which deposits in tissues like the basal ganglia and cornea.
167
What are the main clinical features of Wilson disease?
* Hepatic: acute liver failure, chronic hepatitis, cirrhosis
* Neurologic: parkinsonism, gait disturbance, dysarthria
* Psychiatric: depression, personality changes, psychosis
168
What splenic finding is associated with alcoholic liver disease (ALD) and why?
ALD can cause portal hypertension due to intrahepatic fibrosis and vascular distortion. This leads to splenomegaly from venous congestion, causing expansion of the red pulp in the spleen, which is composed of blood-filled sinuses and reticuloendothelial-lined cords.
169
Why does gynecomastia occur in patients with liver cirrhosis?
Due to hyperestrinism, which results from:
* Increased adrenal production of estrogen precursors (e.g., androstenedione)
* Increased sex hormone–binding globulin, reducing free testosterone
* Impaired hepatic metabolism of estrogen, causing estrogen accumulation
170
What is the role of sex hormone–binding globulin (SHBG) in cirrhosis-related gynecomastia?
Estrogens stimulate SHBG production, which binds testosterone and lowers the free testosterone/estrogen ratio, favoring breast tissue growth.
171
What are spider angiomata and why do they occur in cirrhosis?
Spider angiomata are subcutaneous vascular lesions with a central arteriole and radiating vessels that blanch on compression. They occur due to estrogen-induced arteriolar dilation, and their number correlates with liver disease severity.
172
Which lab tests best reflect the severity and prognosis of liver failure in cirrhosis?
* Serum albumin (low in poor synthetic function)
* Prothrombin time (PT) (prolonged in liver dysfunction)
* Serum bilirubin (elevated when transport/metabolism is impaired)
These tests indicate liver functional reserve and are used in prognostic scoring systems.
173
How do bile acids influence cholesterol gallstone formation?
Bile acids and phospholipids solubilize cholesterol, preventing stone formation. A decrease in bile acids (e.g., due to terminal ileum disease) can lead to cholesterol supersaturation in bile, promoting crystallization and formation of cholesterol gallstones.
174
What are potential complications of Crohn disease (CD) due to its transmural inflammation?
* Strictures: From edema, fibrosis, and hypertrophy → can lead to bowel obstruction
* Fistulas: From deep ulcers forming abnormal connections between organs (e.g., enterovesicular, enterovaginal)
* Abscesses: From walled-off sinus tracts; may perforate, causing peritonitis
175
How does Crohn disease increase the risk of oxalate kidney stones?
In Crohn disease, inflammation of the terminal ileum leads to bile acid loss and fat malabsorption. Unabsorbed fat binds to calcium, preventing calcium from binding dietary oxalate. This increases free oxalate absorption, which is filtered into urine, forming oxalate kidney stones (enteric oxaluria).
176
What is the mnemonic for remembering causes of acute pancreatitis?
“I GET SMASHED”
* I – Idiopathic
* G – Gallstones
* E – Ethanol (alcohol)
* T – Trauma
* S – Steroids
* M – Mumps (and other infections)
* A – Autoimmune
* S – Scorpion sting
* H – Hypertriglyceridemia, Hypercalcemia
* E – ERCP
* D – Drugs (e.g., diuretics, azathioprine, valproic acid)
177
What are the key components of oral rehydration solution (ORS) and their roles?
* Glucose: Enhances sodium absorption via cotransport and provides trivial calories
* Sodium: Maintains intravascular volume (major extracellular osmole)
* Potassium: Replaces loss from diarrhea
* Citrate: Converts to bicarbonate to buffer metabolic acidosis
Total osmolality ≈ 300 mOsm/L
178
CD vs UC and Th1 vs Th2
Chron's = Th1
UC = Th2
179
What causes bleeding in diverticular disease?
Bleeding occurs due to disruption of the vasa recta, small arteries that penetrate the muscular wall of the colon to supply the mucosa. As diverticula form, they stretch and thin the wall, exposing and weakening the vasa recta, which can lead to painless hematochezia (bright red rectal bleeding).
180
What are the different mechanisms of action (MoA) of anticonstipation agents? (6)
1. Bulk-forming laxatives – Bind luminal water to soften stool (e.g., fiber)
2. Osmotic laxatives – Draw water into the lumen (e.g., PEG, lactulose)
3. Surfactants – Lower stool surface tension to allow water entry (e.g., docusate)
4. Stimulant laxatives – Stimulate enteric nerves to increase peristalsis (e.g., senna)
5. Chloride channel agonists – Promote chloride (and water) secretion (e.g., lubiprostone)
6. Peripheral μ-opioid receptor antagonists – Block opioid-induced motility inhibition (e.g., methylnaltrexone)
181
What is hereditary hemochromatosis and its pathophysiology?
Hereditary hemochromatosis is an autosomal recessive disorder caused by a mutation in the HFE gene (e.g., C282Y). It leads to excessive intestinal iron absorption and iron accumulation in parenchymal tissues, causing end-organ damage such as cirrhosis, diabetes mellitus, cardiomyopathy, and arthropathy.
182
What are the functions of transferrin, ferritin, and hepcidin in iron metabolism?
* Transferrin: Binds and transports iron in blood.
* Ferritin: Stores iron inside cells; plasma ferritin reflects body iron stores.
* Hepcidin: Regulates iron absorption and release; inhibits ferroportin to reduce iron levels.
183
How do transferrin, ferritin, and hepcidin levels differ in iron deficiency anemia vs hereditary hemochromatosis?
184
What is the mechanism of action of antiemetic agents used for chemotherapy-induced nausea and vomiting?
* Serotonin (5-HT₃) receptor antagonists (e.g., ondansetron, granisetron): Block 5-HT₃ receptors in the chemoreceptor trigger zone and GI tract
* Neurokinin 1 (NK1) receptor antagonists (e.g., aprepitant, fosaprepitant): Block substance P from binding NK1 receptors in the brainstem
* Dopamine receptor antagonists:
Block D₂ receptors in the chemoreceptor trigger zone (CTZ) of the medulla
185
What is the mechanism of action of antiemetic agents used for motion sickness and hyperemesis gravidarum?
* Antihistamines (e.g., diphenhydramine, meclizine, promethazine): Block H₁ receptors in the vestibular system
* Antimuscarinics (e.g., scopolamine): Block muscarinic receptors in the vestibular nuclei and brainstem
186
What are the differential diagnoses for bilious vomiting in a newborn ?
*Malrotation with midgut volvulus
* Jejunal or ileal atresia
* Hirschsprung disease
* Meconium ileus
* Annular pancreas (less common, extrinsic compression)
Bilious emesis suggests obstruction distal to the ampulla of Vater (i.e., after the second part of the duodenum).
187
What is the pathophysiology of midgut atresia (e.g., jejunal or ileal atresia)?
* Cause: Intrauterine vascular occlusion, often of the superior mesenteric artery
* Leads to ischemia, necrosis, and resorption of affected bowel segments
* Results in a blind-ending proximal bowel and a distal segment coiled around a vessel (”apple peel” or “Christmas tree” atresia)
* Risk factors: Gastroschisis, vasoconstrictive substances (e.g., nicotine), or vascular malformations
188
What is the pathophysiology of duodenal atresia?
* Caused by failure of recanalization of the duodenal lumen after epithelial proliferation during the first trimester
* Leads to complete obstruction typically just distal to the bile duct opening (2nd part of the duodenum)
* Associated with Down syndrome (trisomy 21)
* X-ray shows double bubble sign (dilated stomach and proximal duodenum) with no gas distally
189
What are the common and concerning locations for anal fissures, and what do they suggest about etiology?
* Posterior midline (most common): Due to poor perfusion of posterior anal canal. Sensitive to trauma and slow to heal
* Anterior midline (less common): May be caused by mechanical stress from muscular fiber alignment in the external sphincter
* Lateral fissures (uncommon). Suggest unusual or secondary causes such as: inflammatory bowel disease, Malignancy, Infection
190
What antiemetics are the drug of choice for nausea and vomiting caused by gastrointestinal irritation (e.g., infections, chemotherapy, distention)?
* 5-HT₃ receptor antagonists (e.g., ondansetron)
* They block serotonin receptors on vagal and spinal afferent nerves, which transmit emetogenic signals from the gut to the medullary vomiting center
191
What are the clinical features of fat-soluble vitamin deficiencies (A, D, E, K)?
* Vitamin A: Night blindness, Dry eyes, Bitot spots, Hyperkeratosis
* Vitamin D: Myalgias, bone pain, fractures, Rickets (children), osteomalacia (adults)
* Vitamin E: Ataxia, polyneuropathy, Myopathy, Hemolytic anemia
* Vitamin K: Bleeding diathesis (due to impaired clotting factor activation)
192
What is the most likely cause of bleeding in an exclusively breastfed infant with cystic fibrosis and no vitamin K prophylaxis?
* Vitamin K deficiency
* Due to impaired gamma-carboxylation of factors II, VII, IX, and X
* Worsened by malabsorption of fat-soluble vitamins (A, D, E, K) in cystic fibrosis
* May present with intracranial hemorrhage, especially without neonatal vitamin K injection
193
Watershed regions of the GI tract
