Built from GI Lecture 01 (LOs 1–7). Close notes. Fill from memory. Reveal only after a genuine attempt.

LO 1

ON EXAM — wall layers (inside→out), plexus locations, parietal/chief/G cells, Hirschsprung, skeletal vs smooth muscle

GI segments — fill in primary function for each (LO1)

Segment	Key Feature / Landmark	Primary Function
Stomach	Fundus, body, antrum; rugae; pyloric sphincter
Duodenum	~25 cm; receives bile + pancreatic duct at ampulla of Vater
Jejunum	~2.5 m; most villi/microvilli; most plicae circulares
Ileum	~3.5 m; Peyer's patches; ileocecal valve
Colon	Ascending → transverse → descending → sigmoid; haustra, teniae coli
Anal canal	Internal + external sphincters

Wall layers — name each layer inside → outside and what lives there (LO1)

Layer 1 (innermost)

Layer 2

Layer 3 — two muscle sublayers + what plexus lives between them?

Layer 4 (outermost) — two names, when does each apply?

Plexuses — the "My Sub" mnemonic (LO1)

Mnemonic: MYenteric = Motility (between circular & longitudinal muscle) / SUBmucosal = Secretion (between circular muscle & submucosa)

Plexus	Other Name	Location	Primary Function
Myenteric
Submucosal

Key gastric cell types — fill product/function (LO1)

Cell Type	Location	Product / Function
Parietal cells	Gastric fundus/body
Chief cells	Gastric fundus/body
G cells	Gastric antrum + duodenum
Goblet cells	Throughout SI and colon
Paneth cells	Crypt base (small intestine)
Enteroendocrine cells	Throughout GI tract

Surface area adaptations & skeletal muscle locations (LO1)

3 levels of surface area amplification (name each + fold increase)

Where does the lacteal fit in this structure?

3 locations of skeletal (voluntary) muscle in GI tract

Hirschsprung disease — what fails embryologically? What does the aganglionic segment DO?

LO 2 · LO 3

ON EXAM — DEEP MASS (know all 8), hormones → blood vs enzymes → lumen, fluid volumes, pH gradient, vomiting vs diarrhea acid-base

DEEP MASS — expand each letter with mechanism (LO2)

D — Digestion (enzymatic)

E — Elimination

E — Endocrine function

P — Protection/Immune

M — Motility/Propulsion

A — Absorption

S — Secretion

S — Storage

Hormones vs. enzymes — where do they go? (LO2)

EXAM TRAP: GI hormones (gastrin, CCK, secretin, GIP, GLP-1) are ALWAYS secreted INTO BLOOD, not the lumen. Digestive enzymes (amylase, pepsin, lipase) go INTO THE LUMEN.

Gastrin — source, goes where, what it stimulates

CCK — trigger, goes where, targets

Secretin — trigger, goes where, targets

Pepsin — source, goes where, activation

Fluid volumes — fill in numbers (LO3)

Source	Volume/Day	Key Components
Ingested fluids		Water, electrolytes from diet
Saliva
Gastric juice
Bile
Pancreatic juice
Intestinal secretions		Water, electrolytes, mucus from intestinal crypts
TOTAL entering SI

Fluid absorption — where does all that fluid go? (LO3)

Small intestine absorbs how much?

Colon absorbs how much?

How much is excreted in feces?

Clinical: cholera mechanism and why lethal

pH gradient along GI tract (LO3)

Segment	Approximate pH	What drives it
Mouth / Saliva
Stomach
Duodenum (proximal)
Jejunum
Ileum (terminal)
Colon

Vomiting → what acid-base change and why?

Diarrhea → what acid-base change and why?

Why pepsin works only in stomach

Enteric-coated drugs — target pH for dissolution

LO 4

ON EXAM — ENS autonomy, myenteric vs submucosal, excitatory (ACh/SubP) vs inhibitory (VIP/NO) neurons, ileus types, opioids + μ-receptor

ENS overview — the "second brain" (LO4)

How many neurons in the ENS? Compare to spinal cord.

Can the GI tract function WITHOUT the brain or spinal cord?

What is the role of extrinsic ANS (vagus + sympathetics) relative to ENS?

What happens if you remove ENS entirely (vs. remove extrinsic innervation)?

Two plexuses — comparison table (LO4)

Feature	Myenteric Plexus (Auerbach's)	Submucosal Plexus (Meissner's)
Location
Primary function
Distribution
Stimulus it responds to
Absent in Hirschsprung?

ENS neuron types (LO4)

Excitatory motor neurons — neurotransmitters (2)

Inhibitory motor neurons — neurotransmitters (2)

Sensory (afferent) ENS neurons — what do they detect?

Interneurons in ENS — role

Ileus — types and causes (LO4)

KEY: Ileus = absence of GI motility. ENS cannot function → peristalsis ceases. Three distinct types — know the mechanism of each.

Type	Cause	Mechanism
Paralytic (adynamic)
Hirschsprung
Mechanical obstruction

Opioid mechanism of constipation/ileus — receptor + location

Treatment for opioid-induced constipation without reversing analgesia

LO 5

ON EXAM — 3 receptor types + clinical correlates, peristaltic reflex (ascending ACh/SubP, descending VIP/NO), serotonin 90% in GI, 5-HT3 antagonists vs 5-HT4 agonists, achalasia, VIPoma

Three GI sensory receptor types (LO5)

1. Mechanoreceptors

Stimulus

Primary response

Clinical: post-op ileus mechanism

2. Chemoreceptors

Stimulus

Primary response

Clinical: secretin release trigger + effect

3. Osmoreceptors

Stimulus

Primary response

Clinical: dumping syndrome mechanism

Key GI neurotransmitters — fill effects and associations (LO5)

Neurotransmitter	Effect on GI	High-Yield Association / Clinical
ACh (excitatory)
Substance P (excitatory)
VIP (inhibitory)
Nitric Oxide NO (inhibitory)
Serotonin / 5-HT
Neuropeptide Y (NPY)

Peristaltic reflex — step by step (LO5)

Step 1 — stimulus that triggers the reflex

Step 2 — ascending excitation (proximal/oral side of bolus)

Step 3 — descending inhibition (distal/aboral side of bolus)

Achalasia — which limb fails and why?

Serotonin — what % of body total is in GI? Which cells produce it?

5-HT3 antagonists — drug example + clinical use

5-HT4 agonists — drug example + clinical use

Carcinoid syndrome — mechanism and why RIGHT-sided heart disease only

LO 6

ON EXAM — Celiac/SMA/IMA territories (embryologic origin), watershed zones, portal vein route, lipid exception (lacteals → thoracic duct), portal hypertension consequences

Three GI arteries — fill territories (LO6)

Mnemonic: embryologic — Foregut = Celiac | Midgut = SMA | Hindgut = IMA. Watershed zones are where two supplies border each other → vulnerable to ischemia.

Artery	Embryologic Origin	Structures Supplied (fill in)
Celiac artery
Superior Mesenteric (SMA)
Inferior Mesenteric (IMA)

Watershed zone #1 — where is it and WHY is it vulnerable?

Watershed zone #2

SMA embolism — classic clinical presentation (Step 1 clue)

Celiac artery 3 main branches

Portal circulation & first-pass metabolism (LO6)

Portal vein route — trace the path

Which nutrients go via portal vein? (water-soluble route)

The lipid exception — how do fats bypass the liver?

Clinical significance of lipid bypass (2 points)

Portal hypertension consequences (LO6)

Cirrhosis → ↑ resistance in hepatic sinusoids → portal pressure rises → portosystemic shunts open

Portosystemic Shunt	Location	Clinical Consequence
Esophageal varices
Caput medusae
Hemorrhoids (rectal varices)

LO 7

ON EXAM — Vagus CN X territory (esophagus → transverse colon), pelvic nerve (S2–S4), SNS origin T5–L2, prevertebral ganglia, cephalic phase 20–30%, 3 phases of acid secretion

Parasympathetic — "rest and digest" (LO7)

Feature	Vagus Nerve (CN X)	Pelvic Nerve (S2–S4)
GI Territory
Preganglionic fiber
Postganglionic NT
Effect on GI

Step 1 rule: PSNS GI question anywhere from esophagus to transverse colon → what nerve?

PSNS ganglia location in GI — preganglionic vs postganglionic fiber lengths

Sympathetic — "fight or flight" (LO7)

Feature	Detail
Spinal cord origin
Preganglionic route
Prevertebral ganglia (3)
Postganglionic NT
Effect on motility
Effect on secretion
Effect on blood flow

Cephalic phase (LO7)

The cephalic phase occurs BEFORE food enters the GI tract — triggered purely by CNS anticipation. Mediated by vagal efferents.

Stimuli for cephalic phase

Effects of cephalic phase activation

What % of total gastric acid response is cephalic phase?

Fill in the 3 phases of gastric acid secretion + % each

SNS vs PSNS — quick comparison (LO7)

Effect	PSNS (Vagus / Pelvic)	SNS (Splanchnic nerves)
GI motility
Secretion
Sphincter tone
Splanchnic blood flow
Ganglia location

LO 1–7 · USMLE Step 1 Style

8 questions — cover all 7 LOs. Use these after finishing all tabs.

Q1. A histology slide shows neurons located between the inner circular and outer longitudinal smooth muscle layers of the small intestine. Damage to these neurons would MOST directly impair which function?

A. Mucosal enzyme secretion and local blood flow
B. Coordinated peristalsis and segmentation
C. IgA production and mucosal immune defense
D. Absorption of long-chain fatty acids into lacteals
E. Pancreatic bicarbonate release in response to acid chyme

B — Coordinated peristalsis and segmentation
The myenteric (Auerbach's) plexus lies between the circular and longitudinal muscle layers and controls MOTILITY. The submucosal (Meissner's) plexus, located between circular muscle and submucosa, controls secretion and blood flow (choice A). Choices C–E involve immune, absorptive, and hormonal functions not directly controlled by this plexus location.

Q2. A 3-day-old neonate fails to pass meconium and develops progressive abdominal distension. Rectal biopsy reveals an absence of ganglion cells in the distal rectosigmoid. What embryological event failed, and what would you find in the PROXIMAL dilated segment on biopsy?

A. Failed mesodermal differentiation; absent muscularis mucosae proximally
B. Failed neural crest migration; normal ganglion cells present proximally
C. Failed neural crest migration; absent ganglion cells throughout the colon
D. Defective Wnt signaling; hyperplastic crypts proximally
E. Failed endodermal rotation; volvulus with normal ganglia throughout

B — Failed neural crest migration; normal ganglion cells present proximally
Hirschsprung disease = failure of neural crest cells to migrate into the distal colon during embryogenesis → aganglionic segment → tonic contraction (functional obstruction). The proximal dilated segment has NORMAL ganglia (it dilates because stool cannot pass through the contracted distal segment). This is a classic neonatal surgical emergency.

Q3. A patient is found to have metabolic alkalosis and hypokalemia. Which of the following processes is the MOST likely cause?

A. Profuse watery diarrhea from Vibrio cholerae
B. Prolonged nasogastric suctioning of gastric contents
C. Secretory diarrhea from a VIPoma
D. Pancreatic fistula draining into the peritoneum
E. Ileostomy with high output from the small intestine

B — Prolonged nasogastric suctioning of gastric contents
Loss of gastric fluid (HCl) → loss of H⁺ and Cl⁻ → metabolic ALKALOSIS + hypokalemia (K⁺ shifts into cells as H⁺ exits, and ↑aldosterone from volume depletion causes renal K⁺ wasting). All other choices cause diarrhea → loss of HCO₃⁻-rich intestinal/pancreatic fluid → metabolic ACIDOSIS + hypokalemia.

Q4. A patient on long-term IV opioids for cancer pain develops severe constipation and abdominal distension. The team wants to restore bowel function without reversing analgesia. Which of the following is the BEST option?

A. Naloxone IV (systemic opioid antagonist)
B. Metoclopramide (5-HT4 agonist / D2 antagonist)
C. Methylnaltrexone (peripherally-acting μ-opioid antagonist)
D. Atropine (muscarinic antagonist)
E. Ondansetron (5-HT3 antagonist)

C — Methylnaltrexone (peripherally-acting μ-opioid antagonist)
Opioids bind μ-receptors on ENS neurons → inhibit excitatory NT (ACh/Substance P) → ↓peristalsis + ↑sphincter tone. Methylnaltrexone does NOT cross the BBB, so it blocks the GI μ-receptors without reversing CNS analgesia. Naloxone (A) crosses BBB → would reverse analgesia. Metoclopramide (B) is a prokinetic but does not address the receptor-level cause. Atropine (D) would WORSEN constipation.

Q5. A 68-year-old patient with atrial fibrillation presents with sudden-onset severe periumbilical pain for 2 hours. His abdomen is soft on exam. CT angiography shows an embolus at the origin of the superior mesenteric artery. Which bowel segments are at GREATEST risk for ischemia?

A. Esophagus, stomach, and proximal duodenum
B. Descending colon, sigmoid colon, and upper rectum
C. Distal esophagus, liver, spleen, and gallbladder
D. Jejunum, ileum, cecum, ascending colon, and proximal transverse colon
E. Distal transverse colon, descending colon, and sigmoid colon only

D — Jejunum, ileum, cecum, ascending colon, and proximal transverse colon
The SMA supplies the MIDGUT: duodenum (distal 3rd/4th parts), jejunum, ileum, cecum, ascending colon, and proximal 2/3 of transverse colon. The "pain out of proportion to exam" is the classic Step 1 clue — ischemia causes severe visceral pain mediated by mesenteric afferents before transmural necrosis and peritoneal signs develop. AF = embolic source. Choice A = celiac territory; Choice B/E = IMA; Choice C = celiac.

Q6. A patient develops progressive dysphagia to both solids and liquids. Esophageal manometry reveals failure of the lower esophageal sphincter to relax during swallowing and absence of peristalsis in the distal esophagus. Barium swallow shows a "bird-beak" narrowing at the gastroesophageal junction. Which neurotransmitter deficit BEST explains the pathophysiology?

A. Loss of excitatory ACh + Substance P neurons at LES
B. Excess VIP release causing sustained smooth muscle relaxation
C. Loss of inhibitory VIP/NO neurons at LES → unopposed excitatory tone
D. Excess Substance P causing hypertensive peristalsis
E. Loss of 5-HT3 receptor signaling in ENS afferents

C — Loss of inhibitory VIP/NO neurons at LES → unopposed excitatory tone
Achalasia = selective destruction of inhibitory ENS neurons (nNOS/VIP-positive) at the LES. LES relaxation requires VIP + NO (descending inhibitory limb). Without inhibitory input, unopposed ACh/Substance P excitatory tone → LES stays contracted → food cannot enter stomach → progressive esophageal dilation. Treatments: botulinum toxin (blocks ACh to rebalance), pneumatic dilation, or surgical myotomy (Heller).

Q7. A patient with cirrhosis presents with hematemesis. Endoscopy reveals bleeding esophageal varices. Which statement BEST explains the anatomical basis for variceal formation?

A. Splanchnic arterial vasodilation increases hepatic arterial blood flow
B. Portal hypertension forces blood into portosystemic anastomoses between the left gastric vein and azygos veins
C. Hepatic venous outflow obstruction causes reversal of portal venous flow
D. Inferior mesenteric vein hypertension causes bleeding at the rectosigmoid junction
E. Chylomicron accumulation in the thoracic duct causes esophageal dilation

B — Portal hypertension forces blood into portosystemic anastomoses between the left gastric vein and azygos veins
Cirrhosis → ↑hepatic sinusoidal resistance → portal hypertension → blood backs up into portal tributaries → portosystemic shunts open. At the esophagus: left gastric (portal) ↔ esophageal submucosal veins ↔ azygos vein (systemic). These thin-walled esophageal varices are at high risk of rupture → most dangerous portal HTN complication. Other shunts: caput medusae (paraumbilical veins) and hemorrhoids (superior rectal ↔ inferior/middle rectal).

Q8. A patient smells a meal being prepared and begins salivating with audible stomach growling before eating anything. What is the physiologic name for this phenomenon, and what percentage of total meal-stimulated gastric acid production does it account for?

A. Gastric phase; 60–70% of acid response
B. Intestinal phase; 5–10% of acid response
C. Cephalic phase; 20–30% of acid response
D. Enteric phase; 40–50% of acid response
E. Cephalic phase; 60–70% of acid response

C — Cephalic phase; 20–30% of acid response
The cephalic phase occurs before food even enters the GI tract, triggered by sight/smell/taste/thought of food → cortical + hypothalamic activation → dorsal motor nucleus of vagus → vagal efferents → ENS → ↑HCl, pepsinogen, salivation, and gastric motility. Accounts for ~20–30% of total acid response. Gastric phase (distension + amino acids → gastrin) accounts for 60–70%. Intestinal phase (chyme in duodenum) = 5–10%. Pavlov's "psychic secretion" experiments demonstrated this in dogs.

GI Overview & Physiology — Active Recall