Digestion & Absorption Step 1 Practice Exam

Correct: C — Chylolacteal absorbs fat-soluble vitamins and chylomicrons
The chylolacteal is the central lacteal lymphatic vessel at the core of each small intestinal villus. It is the initial vessel for lymphatic absorption of lipids, fat-soluble vitamins (A, D, E, K), and chylomicrons. These hydrophobic products cannot be directly absorbed into blood capillaries and must enter the lymphatic system via the chylolacteal for transport to the thoracic duct. The capillaries in the villus handle water-soluble nutrients (glucose, amino acids, monosaccharides).

A— Monosaccharides are absorbed via capillaries, not lacteals.
B— Electrolytes are actively transported across epithelial cells into capillaries.
D— PepT1 is an apical transporter for di/tripeptides; products exit via capillaries.
E— B12 is absorbed at the terminal ileum via IF receptors into blood.

Correct: A — Unstirred water layer is rate-limiting for lipid diffusion
The unstirred water layer is a thin aqueous boundary layer adjacent to the intestinal epithelial surface that is not mixed by bulk fluid movement. Fatty acids and monoglycerides must diffuse through this layer to reach the epithelial cell membrane. This diffusion step is often rate-limiting for lipid absorption, especially when lipase activity or micelle formation is adequate. Bile salts enhance absorption by micellarizing lipids, which facilitates their movement through the unstirred layer.

B— Colipase is supplemented; not the issue here.
C— CF does not primarily cause villous atrophy.
D— CF has normal apolipoprotein synthesis.
E— Not a typical CF complication affecting lipid absorption.

Correct: B — Pancreatic lipase hydrolyzes triglycerides to fatty acids and monoglycerides
Pancreatic lipase is the primary lipase secreted by the pancreas that cleaves triglycerides, predominantly at the 1 and 3 positions, yielding two free fatty acids and one 2-monoglyceride. Its deficiency is the primary cause of lipid malabsorption (steatorrhea) in pancreatic insufficiency. Colipase is a cofactor that helps pancreatic lipase access triglycerides in the presence of bile salts.

A— Trypsin digests proteins, not fats.
C— Amylase breaks carbohydrates.
D— Enterokinase is an intestinal enzyme activating trypsinogen; doesn't directly digest fat.
E— Colipase is a cofactor, not the primary enzyme.

Correct: A — Maltose is the primary disaccharide product of amylase
Pancreatic amylase cleaves α-1,4-glycosidic bonds in starch, producing the disaccharide maltose (and small amounts of α-limit dextrin, which has α-1,6 branches). Maltose is then further broken down by brush border maltase into glucose units for absorption.

B— Lactose is a dietary disaccharide (not a starch product); requires lactase.
C— Sucrose is a dietary disaccharide; amylase cannot cleave it (different bond).
D, E— Not products of amylase on starch.

Correct: A — SGLT1 is secondary active (Na+ cotransport); GLUT5 is facilitated diffusion
SGLT1 (sodium-glucose linked transporter 1) is a secondary active transporter coupling glucose (and galactose) uptake to sodium influx down the Na+ gradient maintained by basolateral Na+/K+-ATPase. GLUT5 is a facilitated diffusion transporter specific for fructose; it does not require sodium or ATP. Both are apical transporters. Fructose deficiency explains the patient's fructose malabsorption (osmotic diarrhea).

B— Wrong assignment of substrates and mechanism.
C— GLUT5 does not require ATP.
D— Both are apical; GLUT2 is basolateral (export glucose from enterocyte).
E— GLUT5 operates independently.

Correct: C — Brief intestinal transit limits cellulose fermentation
While humans have colonic microbiota capable of producing cellulases and fermenting fiber, cellulose transit through the small intestine is rapid (~2–4 hours). Most cellulose reaches the colon largely undigested. Although some bacterial fermentation occurs, producing short-chain fatty acids (acetate, propionate, butyrate), the amount is usually modest because: (1) transit time in the colon is only ~12–24 hours; (2) substrate availability may be limiting. Contrast with ruminants, which retain ingesta in the rumen for many hours, allowing extensive microbial fermentation.

A— The colon is not too acidic; pH ~5.5–7 is suitable.
B— Some humans do harbor cellulolytic bacteria.
D— Bile salts are mostly reabsorbed at terminal ileum.
E— Lipase does not digest cellulose.

Correct: B — Primary lactase deficiency with osmotic diarrhea and bacterial H2 production
Primary lactase deficiency (decline in lactase activity after childhood in genetically predisposed individuals) is the mechanism here. Unabsorbed lactose in the small intestine: (1) acts as an osmotic agent, drawing water into the intestinal lumen → osmotic diarrhea (stops with fasting); (2) reaches the colon where commensal bacteria ferment it → hydrogen production detected on breath test. The positive H2 breath test (>20 ppm rise) confirms lactose malabsorption.

A— This is primary, not secondary deficiency.
C— IgE-mediated milk allergy would cause urticaria/anaphylaxis, not just osmotic diarrhea.
D— Only lactase is typically lost; maltase/sucrase preserved.
E— SGLT1 handles the glucose/galactose products of lactose hydrolysis by lactase.

Correct: B — Enterokinase converts trypsinogen to trypsin, initiating protease cascade
Enterokinase (enteropeptidase) is the brush border serine protease that cleaves trypsinogen to activate trypsin. Trypsin then activates other pancreatic zymogens (procarboxypeptidases, proelastase, etc.), creating a proteolytic cascade. Without enterokinase, trypsinogen cannot be activated, and the entire cascade collapses, resulting in severe protein malabsorption despite adequate pancreatic enzyme secretion. His coagulopathy and hypoalbuminemia reflect poor protein/vitamin K absorption.

A— Peptidyl-aminopeptidase is separate and usually adequate.
C— PepT1 is present; the problem is earlier (protease activation).
D— Elastase is secreted; it's not activated.
E— Not the primary defect; leaky gut is a secondary consequence.

Correct: B — Hartnup disease affects apical neutral amino acid transporter; PepT1 intact
Hartnup disease is an autosomal recessive defect in the apical neutral amino acid transporter (related to SLC6A19). It results in inability to absorb free neutral amino acids (including tryptophan) across the apical membrane, leading to: (1) malabsorption and diarrhea; (2) renal wasting (same transporter in kidney); (3) tryptophan deficiency → pellagra-like dermatitis, diarrhea, dementia (the "4 Ds" + ataxia). However, di- and tripeptide absorption via PepT1 remains intact, allowing partial nitrogen salvage if dietary protein is given as peptides.

A— Basolateral exporters are not impaired in Hartnup.
C— Aminopeptidases are still present.
D— Bacterial tryptophanase is secondary.
E— Intestinal architecture is normal in Hartnup.

Correct: B — Bile acids are essential for micellization above CMC
Micelle formation requires bile acids (bile salts) to reach and exceed the critical micellar concentration (CMC), typically ~2–5 mM. Bile salts surround the hydrophobic fatty acids and monoglycerides, forming small spherical structures that facilitate transport through the unstirred water layer to the enterocyte brush border. Without sufficient bile acids, products of lipolysis remain hydrophobic, poorly soluble, and cannot be efficiently absorbed. This explains the fat-soluble vitamin deficiencies (A, D, E, K) and steatorrhea.

A— Gastric function is not impaired.
C— Colipase is usually adequate.
D— Brush border lipase (phospholipase A2) is not the limiting factor.
E— Alkaline phosphatase is not critical for lipid absorption.

Correct: C — MTP transfers triglycerides into apoB-48 chylomicrons
Microsomal triglyceride transfer protein (MTP) is essential for assembling chylomicrons, the lipoprotein vehicles for dietary lipid and fat-soluble vitamin transport. MTP catalyzes the transfer of triglycerides, phospholipids, and cholesteryl esters onto apolipoproteinB-48 (the 48 kDa N-terminal fragment of apoB in enterocytes). Without MTP, absorbed fatty acids and fat-soluble vitamins accumulate as lipid droplets within the enterocyte but cannot be packaged into chylomicrons, preventing their exit into lymph. This results in secondary malabsorption of vitamins A, D, E, K and low serum triglycerides despite normal lipase activity.

A— Micelle formation is intact.
B— Pancreatic function is normal.
D— Mitochondrial function is preserved.
E— Enterocytes do not apoptose.

Correct: C — Abetalipoproteinemia prevents fat-soluble vitamin transport; vitamin E deficiency causes retinitis pigmentosa and neuropathy
Abetalipoproteinemia is a rare autosomal recessive disorder where mutations in APOB prevent synthesis of apolipoprotein B, the structural protein of both chylomicrons (intestinal) and VLDL (hepatic). This blocks transport of fat-soluble vitamins (A, D, E, K) in blood. Vitamin E deficiency is particularly damaging to the nervous system and retina, causing spinocerebellar degeneration, peripheral neuropathy, and retinitis pigmentosa (progressive blindness). Acanthocytes result from abnormal RBC membrane lipid composition due to vitamin E deficiency and abnormal lipid distribution.

A— Carbohydrate absorption is normal.
B— VLDL cannot form (no apoB); hepatic lipid does accumulate but this is secondary.
D— LDL receptors are normal; lipid transport is blocked, not uptake.
E— Protease function is normal.

Correct: B — Loss of terminal ileum removes ASBT, preventing bile acid reabsorption
Enterohepatic circulation of bile acids normally recycles ~95% of the bile acid pool back to the liver daily. The apical sodium-dependent bile acid transporter (ASBT) in the terminal ileum epithelium actively reabsorbs bile salts, returning them to the liver via the portal blood where they are re-secreted into the bile. Ileal resection removes the ASBT-expressing epithelium, reducing reabsorption to ~5%, causing the bile acid pool to become depleted. Fewer bile acids are available for micellization, resulting in steatorrhea and impaired fat-soluble vitamin absorption.

A— Pancreatic lipase is intact.
C— Bacterial overgrowth is not the primary mechanism.
D— Hepatic synthesis increases in response to losses, but cannot fully compensate.
E— Bacterial lipase is not a major factor.

Correct: B — Ileal resection causes B12 deficiency, ADEK deficiency, and hyperoxaluria
Terminal ileum resection has multiple consequences: (1) B12 malabsorption — the terminal ileum is the exclusive site of intrinsic factor (IF)-mediated B12 absorption via cubam receptors; loss → megaloblastic anemia. (2) Fat-soluble vitamin (ADEK) deficiency — loss of ASBT-expressing tissue → depleted bile acid pool → impaired lipid micellization. (3) Hyperoxaluria and oxalate stones — normally oxalate is bound by colonic calcium; bile acid loss → increased colonic fat malabsorption → colonic calcium binds fat instead of oxalate → oxalate hyperabsorption in colon and renal excretion.

A— Multiple deficiencies occur simultaneously.
C— All three malabsorptions are terminal ileum-related.
D— Calcium malabsorption is secondary to vitamin D deficiency, not primary.
E— Bacterial urease is not the mechanism.

Correct: B — Water absorption is osmotically coupled to electrolyte absorption
The small intestine absorbs water largely through osmotic coupling: electrolytes (Na+, Cl−, glucose, amino acids) are actively transported out of the lumen into the bloodstream, creating an osmotic gradient that draws water passively into blood. Water-permeable tight junctions and basolateral aquaporins (AQP3, AQP4) facilitate transcellular water movement. Without adequate solute absorption, there is insufficient osmotic gradient to drive water reabsorption, and it remains in the lumen, causing osmotic diarrhea. This is the basis of osmotic laxatives (magnesium salts, PEG).

A— Aquaporin-2 is renal (ADH-responsive), not intestinal.
C— Tight junctions are stated to be intact.
D— pH effects are not the limiting factor.
E— AQP3 is usually present.

Correct: B — Hepcidin suppresses ferroportin, trapping iron intracellularly
Hepcidin is the master regulator of iron homeostasis, produced by the liver in response to systemic iron and inflammation. Elevated hepcidin (as in anemia of chronic disease/inflammation from rheumatoid arthritis) causes internalization and degradation of ferroportin, the iron exporter on enterocytes and macrophages. This results in iron sequestration — adequate iron in stores but unable to be mobilized for hemoglobin synthesis, causing anemia despite normal dietary iron and iron availability.

A— DMT1 is actually upregulated when iron is low, but hepcidin effects dominate.
C— Villous architecture is intact.
D— Copper deficiency is not present.
E— No mention of blood loss; stores are high.

Correct: C — Low 1,25-vitamin D impairs intestinal calbindin induction and calcium absorption
1,25-dihydroxyvitamin D (the active hormone form) acts as a ligand for the vitamin D receptor (VDR) in intestinal epithelial cells, inducing expression of calbindin-D9k, a cytoplasmic calcium-binding protein essential for transcellular calcium absorption. Without adequate 1,25-vitamin D, calbindin is not induced, calcium transport is impaired, and hypocalcemia results. In this patient, the low 1,25-vitamin D suggests impaired renal 1-α-hydroxylase activity (possibly from thyroid autoimmunity affecting other endocrine axes, or intrinsic renal disease). With normal kidney function and adequate 25-OH vitamin D substrate, the block is in conversion.

A— Dietary calcium is often adequate in hypocalcemia; malabsorption is the issue.
B— Achlorhydria is unlikely; pH effects are minor compared to 1,25-vitamin D.
D— VDR is intact (secondary hyperparathyroidism indicates responsiveness).
E— Na/Ca exchanger is usually adequate.

Correct: B — Gastrectomy removes IF-producing parietal cells; IF-B12 absorption at terminal ileum is lost
The vitamin B12 absorption pathway requires: (1) Intrinsic factor (IF) secreted by gastric parietal cells; (2) IF binds B12 (cobalamin) in the stomach; (3) R factor (transcobalamin I/haptocorrin) from saliva initially binds B12 but is cleaved by pancreatic proteases, releasing B12 to IF; (4) IF-B12 complex is absorbed at the terminal ileum via cubam receptors (specialized IF-B12 absorbers); (5) Transcobalamin II (TC2) carries B12 in plasma. Gastrectomy eliminates IF production → B12 cannot be absorbed despite adequate intake.

A— Correct mechanism but not best stated.
C— R factor degradation is normal; IF deficiency is the issue.
D— No villous atrophy mentioned.
E— TC2 transports B12 after absorption; deficiency does not block uptake.

Correct: B — Cholera toxin causes secretory diarrhea via cAMP-mediated Cl− secretion
Secretory diarrhea is caused by toxins or hormones that increase intracellular signaling (cAMP, cGMP) in enterocytes, leading to active Cl− secretion into the lumen, with water following osmotically. Cholera toxin (from V. cholerae) ADP-ribosylates Gs protein, locking it in the active state → persistent cAMP elevation → sustained Cl− secretion. Key features: (1) continues during fasting (no substrate needed); (2) continues at night (not dependent on feeding); (3) large osmotic gap (>125 mOsm/kg indicates secretory, not osmotic); (4) stool electrolytes approach plasma.

A— Osmotic diarrhea stops with fasting; this does not.
C— V. cholerae does not invade; it's toxin-mediated.
D— No fat malabsorption here.
E— Motility is not the mechanism.

Correct: C — Villous atrophy reduces brush border surface and disaccharidase-bearing enterocytes
Secondary disaccharidase deficiency occurs when small intestinal disease damages the villous architecture, reducing the total number of brush border-bearing enterocytes and thus enzyme content. This patient has tropical sprue, a chronic infectious/inflammatory condition causing villous atrophy and nutrient malabsorption. His partial villous atrophy (height/crypt ratio 3:1, normal >5:1) reduces lactase (and other disaccharidases) activity, causing secondary lactose malabsorption detectable on hydrogen breath test. Unlike primary lactase deficiency (genetic), this is reversible with mucosal healing. His B12 and folate deficiency reflect mucosal damage and inflammation.

A— This is secondary, not primary lactase deficiency.
B— Pancreatic function is not impaired in sprue.
D— Bacterial metabolism is not the direct mechanism.
E— Not immune-mediated destruction.