What is the functional significance of lacteals in intestinal villi?
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Answer
Lacteals are lymphatic capillaries that absorb chylomicrons (too large for blood capillaries). Chylomicrons bypass portal blood and enter lymph → thoracic duct → systemic circulation.
LO 2 — Unstirred Water Layer
How do bile salt micelles overcome the rate-limiting step of the unstirred water layer?
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Answer
Micelles are amphipathic (hydrophobic core, hydrophilic exterior) → ferry lipid digestion products across the unstirred water layer. Without micelles, fat-soluble compounds cannot traverse the UWL efficiently → steatorrhea.
LO 3 — Principal Enzymes
Which enzyme is the "master activator" of the pancreatic protease cascade, and where is it produced?
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Answer
Enterokinase (enteropeptidase) — produced by duodenal brush border. Cleaves trypsinogen → trypsin, which then activates all other zymogens (chymotrypsinogen, proelastase, procarboxypeptidases).
LO 4 — Transport Mechanisms
Name the four main mechanisms of nutrient absorption across the enterocyte membrane.
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Answer
1) Primary active transport (Na+/K+-ATPase, ATP-driven). 2) Secondary active transport (co-transport via Na+ gradient: SGLT1, PepT1). 3) Facilitated diffusion (GLUT5, GLUT2). 4) Passive diffusion (lipids, water).
LO 5 — Fiber
Why is cellulose (dietary fiber) not digested by human enzymes?
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Answer
Cellulose is a glucose polymer with β-1,4 glycosidic bonds. Human digestive enzymes (amylase, maltase) only cleave α-glycosidic bonds. No cellulase (β-glucosidase) is produced → cellulose passes through undigested.
LO 6 — Carbohydrate Digestion
What is the two-phase process of starch digestion, and which enzyme dominates in each phase?
What is PepT1, and why is di/tripeptide absorption more efficient than free amino acid absorption?
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Answer
PepT1 = H+-peptide cotransporter (secondary active, H+-gradient from Na+/H+ antiporter). Di/tripeptides are absorbed intact via PepT1, then hydrolyzed by cytoplasmic peptidases. PepT1 pathway is more efficient than multiple free amino acid transporters.
LO 11 — Lipid Digestion
Describe the role of pancreatic lipase and co-lipase in triglyceride digestion.
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Answer
Pancreatic lipase cleaves sn-1 & sn-3 ester bonds → 2-monoglyceride + 2 free fatty acids. Co-lipase (activated by trypsin) anchors lipase at the lipid-water interface, preventing bile salt inhibition. Without co-lipase: bile salts displace lipase → steatorrhea.
LO 12 — Micelle Formation
What is a mixed micelle, and what role do bile salts play in its formation and function?
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Answer
Mixed micelle: 4–8 nm cylindrical structure with hydrophobic core (2-MAG, FA, cholesterol, vitamins) + hydrophilic exterior. Bile salts (amphipathic) are essential: they emulsify large TG droplets → increase lipase substrate area AND form micelles to ferry lipids across the unstirred water layer.
LO 13 — Chylomicron Assembly
What happens to lipid digestion products inside the enterocyte, and how is chylomicron formed?
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Answer
Lipids diffuse across enterocyte membrane → carried to SER by FABP → re-esterification (2-MAG + 2 FA → TG). Assembled with cholesterol esters, phospholipids, apoB-48 (unique intestinal form) → chylomicrons → Golgi → basolateral exocytosis → lacteals (not portal blood, too large).
LO 14 — Abetalipoproteinemia
What is the genetic defect in abetalipoproteinemia, and why does it cause steatorrhea and fat-soluble vitamin deficiency?
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Answer
Defect: Microsomal triglyceride transfer protein (MTP) mutation → cannot assemble apoB-48-containing chylomicrons. Fat accumulates in enterocytes (cannot be exported) → steatorrhea. Fat-soluble vitamins (A, D, E, K) malabsorbed → vitamin E deficiency causes spinocerebellar degeneration (ataxia).
LO 15 — Bile Acid Circulation
Where and how are conjugated bile acids reabsorbed, and what percentage are recycled daily?
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Answer
Conjugated bile acids are actively reabsorbed in the terminal ileum via ASBT (apical sodium-dependent bile acid transporter) — Na+-bile acid co-transport. Recycled 6–10 times daily. ~95% of bile acids conserved; only ~5% lost daily (replenished by hepatic synthesis).
LO 16 — Ileal Resection
What are the three major consequences of terminal ileum resection exceeding 100 cm?
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Answer
1) Bile acid diarrhea: Loss of active reabsorption → ↑ colonic bile acids stimulate water secretion. 2) Fat malabsorption: Depleted bile acid pool → ↓ micelle formation → steatorrhea. 3) Vitamin B12 deficiency: Terminal ileum required for B12-IF absorption → megaloblastic anemia.
LO 17 — Water & Electrolyte Absorption
What is the net effect of Na+ absorption on water absorption in the small intestine?
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Answer
Na+ absorption (via Na+/K+-ATPase, SGLT1, NaCl co-transporters) creates an osmotic gradient → water follows osmotically into portal blood. Most water absorption is secondary to electrolyte absorption. This is why cholera (CFTR overactivation) causes massive watery diarrhea despite normal Na+ gradient.
LO 18 — Iron Absorption
Trace the pathway of dietary iron from the intestinal lumen to incorporation into transferrin in portal blood.
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Answer
Fe³⁺ → ferrireductase (apical) → Fe²⁺ → DMT1 (divalent metal transporter, H+-coupled) → iron enters enterocyte. Stored as ferritin; basolateral exit via ferroportin → hephaestin oxidizes Fe²⁺ → Fe³⁺ → binds transferrin in portal blood.
LO 19 — Calcium Absorption
What is the role of vitamin D, PTH, and calbindin in active calcium absorption?
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Answer
PTH stimulates 1,25-(OH)₂-vitamin D₃ synthesis (renal). Vitamin D induces calbindin (CaBP) synthesis in enterocytes. Calbindin binds apical Ca²⁺ (via TRPV6) → intracellular buffering → basolateral Ca²⁺-ATPase extrudes Ca²⁺ into portal blood. Vitamin D also ↑ TRPV6 and Ca²⁺-ATPase expression.
LO 20 — Fat-Soluble Vitamins
What is the main prerequisite for absorption of fat-soluble vitamins (A, D, E, K)?
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Answer
Micelle formation. Fat-soluble vitamins must be incorporated into mixed micelles (with bile salts) to cross the unstirred water layer. Any condition reducing bile salt delivery (cholestasis, ileal disease, CF) → fat-soluble vitamin malabsorption → deficiency diseases (night blindness, osteomalacia, bleeding tendency, neurologic symptoms).
LO 20 — Vitamin B12 Pathway
Describe the B12 absorption pathway from dietary source to terminal ileum.
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Answer
B12 released from food proteins by gastric acid/pepsin → bound by transcobalamin I (TC1) in saliva → intrinsic factor (IF) (gastric parietal cells) binds B12 → B12-IF complex → terminal ileum receptor (cubilin-amnionless) → absorbed → bound by transcobalamin II (TC2) in blood.
LO 21 — Osmotic vs. Secretory Diarrhea
Differentiate osmotic and secretory diarrhea by their response to fasting and stool osmolar gap.
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Answer
Osmotic diarrhea: Stops with fasting; stool osmolar gap > 50 mOsm/kg (caused by unabsorbed solutes). Examples: lactose intolerance, magnesium supplement. Secretory diarrhea: Continues despite fasting; normal osmolar gap (active water secretion). Examples: cholera, VIPoma, celiac disease.
Question 1
The small intestine achieves ~______-fold increase in absorptive surface area compared to a smooth tube of the same length, through three levels of amplification: plicae circulares, villi, and microvilli.
Hint: It's between 400–800.
Question 2
Salivary amylase is inactivated by ______ in the stomach and accounts for only ~______% of total starch digestion.
Hint: The first blank is a low pH environment; the second is a small percentage.
Question 3
SGLT1 transports ______ and ______ via secondary active co-transport with ______. Mutations in SGLT1 cause glucose-galactose malabsorption and osmotic diarrhea.
Hint: Two monosaccharides and one electrolyte.
Question 4
Pepsin is activated in the stomach at pH ______ and is inactivated in the duodenum when pH rises above ______.
Hint: The first is acidic; the second is when the lumen becomes less acidic.
Question 5
Pancreatic lipase cleaves the ______ ester bonds of triglycerides, producing ______ and two free fatty acids.
Hint: Think about the positions on the glycerol backbone (numbered 1, 2, 3).
Question 6
______ is the H+-peptide cotransporter that absorbs di- and tripeptides MORE efficiently than free amino acids because it uses the proton gradient generated by the ______.
Hint: One is a transporter acronym; the other involves a Na+ antiporter.
Question 7
______ is the protein that anchors pancreatic lipase at the lipid-water interface to prevent bile salt inhibition. Without it, bile salts competitively displace lipase and cause steatorrhea.
Hint: It's a pancreatic protein co-secreted with lipase (abbreviated).
Question 8
In abetalipoproteinemia, the genetic defect is in ______, which prevents assembly of ______-containing lipoproteins. This causes fat to accumulate in enterocytes and results in steatorrhea.
Hint: One is a lipid transfer protein; the other is an apolipoprotein.
Question 9
Bile acids are recycled ______ times per day. Conjugated bile acids are actively reabsorbed in the ______ via the transporter ______.
Hint: 6–10 cycles daily; the intestinal segment has a special name; the transporter is an acronym.
Question 10
Iron is transported across the apical membrane via ______ (a divalent metal transporter), and is exported from the enterocyte basolaterally via ______. Intracellular iron is stored as ______.
Hint: Three proteins involved in iron handling.
Drag items to their correct sequential order, then click "Check Order" to verify. Click "Reveal Answer" to see the solution.
Starch Digestion Sequence
Order the steps of starch digestion from mouth to monosaccharide absorption.
Identify whether each statement is TRUE or FALSE, then click "True" or "False" to reveal the explanation and correct answer.
Trap 1
Micelles are absorbed intact into enterocytes and contribute to chylomicron formation.
CORRECT ANSWER: False. Micelles ferry lipid digestion products across the unstirred water layer, but the products (2-MAG, FA, cholesterol) diffuse OUT of the micelle at the brush border and passively enter the enterocyte. Bile salts remain in the lumen and are recycled in the terminal ileum. Only the absorbed lipids are re-esterified and packaged into chylomicrons.
Trap 2
Lactose intolerance is caused by bacterial overgrowth in the small intestine due to undigested lactose.
CORRECT ANSWER: False (partially). Undigested lactose does reach the colon (not overgrowth in SI), where normal colonic bacteria ferment it → osmotic diarrhea (main mechanism) + gas production (bloating, flatulence). The osmotic effect is the primary cause of symptoms.
Trap 3
Pancreatic lipase requires no accessory factor to cleave triglycerides in the presence of bile salts.
CORRECT ANSWER: False. Pancreatic lipase REQUIRES co-lipase because bile salts competitively inhibit lipase by displacing it from the lipid-water interface. Co-lipase (activated by trypsin) anchors lipase at the interface, restoring activity. Without co-lipase, steatorrhea ensues.
Trap 4
Free amino acids are absorbed more efficiently than dipeptides and tripeptides because of their higher concentration.
CORRECT ANSWER: False. Di/tripeptides are absorbed MORE efficiently than free amino acids despite lower concentration, because PepT1 (H+-peptide cotransporter) is high-affinity and utilizes the proton gradient from the Na+/H+ antiporter. Free AAs use multiple lower-efficiency transporters.
Trap 5
Terminal ileum resection only affects fat absorption and has no impact on carbohydrate or protein absorption.
CORRECT ANSWER: False. Terminal ileum resection has TWO major consequences: (1) Loss of bile acid reabsorption → cholerheic diarrhea + fat malabsorption. (2) Loss of B12-IF absorption site → vitamin B12 deficiency → megaloblastic anemia. The ileum is also the site of some mineral absorption.
Trap 6
Abetalipoproteinemia is caused by mutations in the APOB gene encoding apoB-100.
CORRECT ANSWER: False. Abetalipoproteinemia is caused by mutations in the MTP gene (microsomal triglyceride transfer protein), not APOB. Familial hypobetalipoproteinemia (milder) is caused by APOB mutations. MTP mutations prevent assembly of ALL apoB-containing lipoproteins → severe fat malabsorption.
Trap 7
Osmotic diarrhea from lactose intolerance continues despite fasting, whereas secretory diarrhea stops with fasting.
CORRECT ANSWER: False (reversed).Osmotic diarrhea STOPS with fasting (lactose removed from lumen). Secretory diarrhea CONTINUES despite fasting (active water secretion). Stool osmolar gap differentiates: osmotic > 50 mOsm/kg; secretory normal.
Trap 8
Congenital enterokinase deficiency would present similarly to severe pancreatic exocrine insufficiency with low amylase and lipase levels.
CORRECT ANSWER: False. Enterokinase deficiency presents with protein malabsorption (failure to thrive, hypoproteinemia) BUT amylase and lipase are NORMAL because they are produced by the pancreas—the problem is activation. Pancreatic insufficiency has ↓ amylase/lipase. This distinction is key on exams.
Principal Digestive Enzymes — Location, Substrate, Product
Enzyme
Source
Substrate
Product
Salivary amylase
Parotid, submandibular glands
Starch (α-1,4 bonds)
Oligosaccharides, maltose
Lingual lipase
Tongue (von Ebner's glands)
Triglycerides (short/medium-chain)
Diglycerides + fatty acids
Gastric lipase
Gastric chief cells
Triglycerides (mainly short/medium-chain)
Diglycerides + fatty acids
Pepsin
Gastric chief cells (as pepsinogen)
Proteins (Phe, Trp, Tyr bonds)
Large peptide fragments
Pancreatic amylase
Exocrine pancreas
Starch, glycogen (α-1,4 bonds)
Maltose, maltotriose, α-limit dextrins
Pancreatic lipase
Exocrine pancreas (+ co-lipase)
Triglycerides (sn-1,3 positions)
2-monoglyceride + 2 free fatty acids
Enterokinase
Duodenal brush border
Trypsinogen
Trypsin (master activator)
Trypsin
Pancreas (activated by enterokinase)
Proteins (Arg/Lys bonds)
Peptides + activates other zymogens
Chymotrypsin
Pancreas (activated by trypsin)
Proteins (aromatic AA bonds)
Peptides
Lactase
Brush border (jejunum)
Lactose
Glucose + galactose
Maltase
Brush border
Maltose, maltotriose
Glucose
Sucrase-isomaltase
Brush border (jejunum)
Sucrose, α-limit dextrins
Glucose + fructose; glucose
Key: Memorize source, substrate, and product for each enzyme. Board exams frequently test knowledge of which enzyme acts where and what happens when deficient (e.g., lactase deficiency → lactose intolerance; enterokinase deficiency → protein malabsorption but normal amylase/lipase).
Lipid products, water, unconjugated bile acids, long-chain FA
Paracellular transport
Electrochemical gradient
Tight junctions
Water, Cl−, some ions (proximal SI)
Critical concept: Na+/K+-ATPase maintains the Na+ gradient across the basolateral membrane. This gradient is the "engine" driving secondary active transport of glucose, amino acids, peptides, and even chloride in the small intestine.
Lipid Digestion Roadmap: From Dietary Fat to Chylomicron
Step
Location
Key Players
Product(s)
1. Emulsification
Stomach + duodenum
Gastric churning, bile salts
Small lipid droplets (~1–2 µm)
2. Lingual & gastric lipase
Mouth, stomach
Lingual lipase, gastric lipase
~10–30% TG digestion (short/medium-chain)
3. Pancreatic lipase + co-lipase
Duodenum
Pancreatic lipase, co-lipase, bile salts
2-monoglyceride + 2 free fatty acids (70–80% TG)
4. Micelle formation
Lumen
Bile salts, lipase products
Mixed micelles (4–8 nm) — cross unstirred water layer