Built from GI Lecture 05 (LOs 1–4). Close notes. Fill from memory. Reveal only after a genuine attempt.

LO 1

ON EXAM — What the UWL is and how it forms, why lipids are the exception (hydrophobic aggregation), micelle as amphipathic carrier, bile does NOT digest (pancreatic lipase does), bile stays in lumen after delivery

The Unstirred Water Layer — fill the blanks

UWL definition — what is it?

2 factors that create it

UWL function (barrier type)

What enterocytes also secrete here (acid protection)

Why Lipids Are the Exception

Lipids are ___ (property) in the aqueous lumen

In aqueous lumen, lipids form ___

These cannot diffuse through the ___

Without bile, dietary fat would ___

Bile as the Lipid Carrier — Micelle Mechanics

Micelle = small ___ vesicles

Hydrophobic ends face ___ (doing what?)

Hydrophilic ends face ___ (doing what?)

After delivering lipids, bile itself does what? (enters enterocyte?)

KEY: Bile emulsifies lipids — does it DIGEST them? Who does?

Emulsification = breaks large fat droplets into ___ (why it matters)

Lipids passively diffuse off micelle because they are ___

After delivery, bile travels down to ___ for recycling

LO 2

ON EXAM — Bile made in hepatocytes from cholesterol (HMG-CoA reductase / statins), glycocholic acid = conjugation with glycine, primary bile = amphipathic, secondary bile = gut bacteria strip hydrophilic end, bilirubin excretion: obstructive jaundice signs, cholestyramine

Hepatocyte Bile Synthesis

Bile is synthesized exclusively in ___

Bile backbone (lipophilic component)

Rate-limiting enzyme for cholesterol synthesis

Statin mechanism + relevance to bile

Other bile contents besides bile acids (3 things)

Glycocholic Acid — Making Bile Amphipathic

Conjugation: glycine added to cholesterol backbone → forms

Why conjugation matters (what does adding glycine/taurine give?)

Net structural property of primary bile

Primary vs Secondary Bile — fill both columns

Property	Primary Bile	Secondary Bile
Origin
Structure
Location
Micelle Formation?
Examples

Bilirubin Excretion — fill the blanks

Unconjugated bilirubin (indirect): properties + transport

How hepatocytes conjugate bilirubin (what do they add?)

In gut: conjugated bilirubin converted to ___ (stool color)

Obstructive jaundice triad: 3 signs

Cholestyramine: mechanism + 2 clinical uses

LO 3

ON EXAM — CCK (I-cells, 4 effects), secretin + HCO₃⁻, solvent drag, ZE syndrome inactivates bile + lipase, enterohepatic circulation (10% lost, terminal ileum ASBT, 6-10x/day), terminal ileum resection consequences, 3 gallstone types + 5 F’s, gallstone complications

CCK — Hormonal Regulation of Bile Secretion

CCK: released by ___ cells in the ___

Trigger for CCK release

CCK Effect	Target	Result
Effect 1	Hepatocytes
Effect 2	Gallbladder smooth muscle
Effect 3	Sphincter of Oddi
Effect 4 (bonus)	Pancreatic acinar cells

Secretin: released by ___ cells; stimulates ___

Bile as Osmotic Agent & Buffer

Bile is osmotically active → draws ___ into lumen (= solvent drag)

Solvent drag pulls along (ions)

Bile acid malabsorption causes (consequence in colon)

Bile contains ___ → alkaline → neutralizes acid chyme arriving from stomach

Zollinger-Ellison + fat malabsorption: mechanism

Enterohepatic Circulation — The Recycling Loop

Primary bile reabsorbed at ___ (where in GI tract)

Transporter responsible for reabsorption

Returns to liver via ___

% of bile lost in feces per cycle

Times bile pool is recycled per day

Terminal ileum resection — 4 consequences

Gallstones (Cholelithiasis) — fill the table

Type	Composition	Risk Factors	Radiology
Cholesterol (~80%)
Black Pigment
Brown Pigment

LO 4

ON EXAM — Micelle orientation (hydrophilic out), lipid cargo, emulsification vs micelle distinction, colipase mechanism (pro-colipase → trypsin → colipase → opens door for pancreatic lipase), lipase products (2 FA + 1 MG), chylomicrons → lacteals, fat malabsorption causes (7), fat-soluble vitamins (ADEK), PBC vs PSC antibodies

Micelle Structure

Orientation of bile: hydrophilic ends face ___ (doing what?); hydrophobic ends face ___ (doing what?)

Lipid cargo inside micelle (4 things)

Emulsification: what does bile do? (before micelle assembly)

Micelle formation: what does it accomplish? (distinct from emulsification)

The Colipase Problem & Solution

Why bile BLOCKS pancreatic lipase

Pro-colipase is activated by ___

Colipase binds ___ and does ___

Result: pancreatic lipase can now ___

Products of pancreatic lipase digestion of 1 triglyceride

After enterocyte uptake: fatty acids → re-esterified → ___ → enter ___ → thoracic duct

Fat Malabsorption Causes — fill the key fact

Mechanism	Example	Key Fact / Result
↓ Bile production	Liver failure, PBC, PSC
Bile duct obstruction	Gallstones, pancreatic cancer
↓ Bile reabsorption	Terminal ileum resection, Crohn’s
↓ Pancreatic lipase	Chronic pancreatitis, CF
Acid inactivation	Zollinger-Ellison syndrome
Mucosal damage	Celiac, Whipple disease
↓ Chylomicron formation	Abetalipoproteinemia

Fat-Soluble Vitamin Deficiencies (ADEK)

Vitamin	Deficiency Findings
Vitamin A
Vitamin D
Vitamin E
Vitamin K

PBC vs PSC — fill the distinguishing features

Feature	PBC	PSC
Demographics
Antibody
Ducts affected
Key complication
Treatment

⚠️ Both PBC and PSC cause cholestasis → steatorrhea → fat-soluble vitamin deficiency (A, D, E, K).

Practice Qs — LOs 1–4

USMLE Step 1 & In-House Style — attempt all before revealing answers

Q1 (LO1) A researcher finds that dietary lipids cannot cross a stagnant aqueous zone adjacent to enterocytes without a carrier. Why can’t lipids cross this zone unaided?

A. Too large for aquaporin channels B. Hydrophobic → aggregate in aqueous lumen → cannot diffuse through the aqueous UWL C. Require ATP-dependent transporters D. Negatively charged, repelled by glycocalyx E. Acidic mucus repels them

B — Hydrophobic aggregation prevents UWL crossing. The UWL is aqueous. Lipids aggregate into large hydrophobic droplets and cannot diffuse through this aqueous zone. They need an amphipathic carrier — the micelle. Key trap: once lipids reach the enterocyte membrane they diffuse right through it (lipophilic → loves lipid bilayer) — the problem is crossing the aqueous UWL first.

Q2 (LO1/2) A student asks: "If bile can’t chemically digest fat, why is it essential for fat absorption?" Which best describes bile’s role?

A. Bile hydrolyzes triglycerides into fatty acids B. Bile activates pancreatic lipase by phosphorylation C. Bile emulsifies fat globules and forms micelles to carry lipids through the UWL D. Bile provides the alkaline pH for lipase E. Bile transports fatty acids via receptor-mediated endocytosis

C — Bile emulsifies + forms micelles. Bile is a detergent (emulsifier) — NOT a digestive enzyme. It (1) breaks large fat globules into smaller ones (emulsification → ↑ surface area for lipase) and (2) packages lipid fragments into micelles to carry them through the aqueous UWL. Triglyceride hydrolysis is done by pancreatic lipase. The alkaline pH comes from HCO₃⁻ in bile + pancreatic secretions.

Q3 (LO2) A 52-year-old man is started on atorvastatin for hypercholesterolemia. The drug blocks the rate-limiting enzyme in cholesterol synthesis. Name the enzyme and explain its relevance to primary bile acid production.

A. Fatty acid synthase; reduces phospholipid component of bile B. HMG-CoA reductase; directly reduces cholesterol backbone of primary bile acids C. Cholesterol 7α-hydroxylase; reduces bilirubin secretion D. HMG-CoA synthase; reduces triglyceride component of bile E. Acetyl-CoA carboxylase; reduces glycine conjugate

B — HMG-CoA reductase; cholesterol backbone of primary bile acids. Primary bile acids (glycocholic acid, taurocholic acid) are made from a cholesterol backbone. HMG-CoA reductase is rate-limiting for cholesterol synthesis → statins inhibit this enzyme → ↓ intracellular cholesterol → hepatocytes upregulate LDL receptors → ↓ serum LDL. Also reduces primary bile synthesis. Side effect: myopathy (↑ CK); risk ↑ with fibrates.

Q4 (LO2) A 45-year-old woman has progressive jaundice, pruritus, xanthelasma, and elevated alkaline phosphatase. Biopsy: granulomatous destruction of intrahepatic bile ducts. Labs: positive anti-mitochondrial antibody (AMA). Diagnosis + effect on fat absorption?

A. PSC; normal fat absorption B. PBC; steatorrhea and fat-soluble vitamin deficiency C. Autoimmune hepatitis; protein malabsorption only D. Biliary atresia; corrected by UDCA E. Wilson disease; copper accumulation causing fat malabsorption

B — PBC; steatorrhea + fat-soluble vitamin deficiency (ADEK). PBC = autoimmune destruction of intrahepatic bile ducts in middle-aged women; AMA is the hallmark antibody. Destroyed bile ducts → cholestasis → ↓ bile delivery → impaired micelle formation → steatorrhea + vitamin ADEK deficiency. PSC (young men + UC + p-ANCA + "beads on string" ERCP) is a different entity. Treatment: ursodeoxycholic acid (UDCA).

Q5 (LO3) A 28-year-old woman with gallstones develops RUQ pain after eating a high-fat meal. Which hormone triggered her gallbladder contraction, and what are its three biliary effects?

A. Secretin; ↑ HCO₃⁻, relaxes sphincter of Oddi, contracts gallbladder B. Gastrin; ↑ acid, stimulates bile, relaxes pylorus C. CCK; ↑ bile production, contracts gallbladder, relaxes sphincter of Oddi D. GIP; inhibits acid, relaxes gallbladder, ↓ bile E. Motilin; ↑ motility, contracts gallbladder, ↓ bile reabsorption

C — CCK; three biliary effects: ↑ bile production, gallbladder contraction, sphincter of Oddi relaxation. Fat + protein in duodenum → I-cells release CCK → (1) ↑ bile production at liver, (2) rhythmic gallbladder contraction (releases stored bile), (3) relaxes sphincter of Oddi (bile enters duodenum). CCK also stimulates pancreatic enzyme secretion (lipase, proteases, amylase). Gallbladder contracting against a cystic duct stone = biliary colic.

Q6 (LO3) A patient with Crohn’s disease undergoes resection of 120 cm of terminal ileum. Postoperatively she has watery diarrhea and steatorrhea. What is the primary mechanism of diarrhea?

A. Bacterial overgrowth → protein fermentation B. Bile acid malabsorption → bile acids enter colon → osmotic/secretory diarrhea C. Loss of ileocecal valve → rapid transit D. ↓ Gastric acid from loss of ileal enterocytes E. Loss of disaccharidase enzymes → carbohydrate malabsorption

B — Bile acid malabsorption → bile acids enter colon → watery diarrhea. Terminal ileum = primary site for active bile acid reabsorption (ASBT transporter). After resection, unabsorbed bile acids enter the colon → osmotic + secretory diarrhea. Also: depleted bile pool → steatorrhea; B₁₂ deficiency (IF-B₁₂ absorbed here); fat-soluble vitamin deficiency (ADEK). Treat bile acid diarrhea with cholestyramine.

Q7 (LO4) A researcher finds that pancreatic lipase cannot digest triglycerides within micelles because the hydrophilic ends of bile form a blocking shell. What mechanism overcomes this?

A. Secretin cleaves pro-colipase → colipase displaces bile B. Trypsin cleaves pro-colipase → colipase binds hydrophilic ends of bile → opens access for pancreatic lipase C. Enterokinase directly activates colipase → digests bile conjugates D. CCK activates pancreatic lipase by phosphorylation E. Bile spontaneously deconjugates at the micelle surface

B — Trypsin → colipase → opens door for pancreatic lipase. Pro-colipase (from pancreas) is activated by trypsin. Active colipase binds the hydrophilic ends of bile molecules on the micelle surface, displacing them and creating a "door" for pancreatic lipase. Lipase hydrolyzes triglycerides → 2 fatty acids + 1 monoglyceride. Without colipase, fat digestion in the SI fails even if bile and lipase are both present.

Q8 (LO4) A 48-year-old alcoholic has greasy floating stools, easy bruising, and elevated PT/INR. Which fat-soluble vitamin deficiency best explains the coagulopathy?

A. Vitamin A B. Vitamin D C. Vitamin E D. Vitamin K E. Vitamin C

D — Vitamin K deficiency. Vitamin K is required for γ-carboxylation of coagulation factors II, VII, IX, X + protein C and S. Deficiency → ↑ PT/INR → easy bruising and bleeding. Alcoholism → liver disease + fat malabsorption (pancreatitis, impaired bile) → steatorrhea → malabsorption of all fat-soluble vitamins. Vitamin A = night blindness; Vitamin D = osteomalacia/rickets; Vitamin E = ataxia/hemolytic anemia. Vitamin C is water-soluble (causes scurvy, not elevated PT).

Bile Workshop & Making a Micelle — Active Recall