The stomach

Primary active transport spends ATP directly, as the sodium–potassium pump does. Using a gradient built by another pump is secondary active transport; moving down a gradient is passive.

• Correct: It uses ATP directly to move a substance against its gradient:
• It lets a substance move down its gradient through a channel:
• It uses the sodium gradient built by another pump:

Carbonic anhydrase speeds CO2 + H2O ⇌ H2CO3, which splits into H+ and bicarbonate.

• The splitting of ATP:
• Correct: The reaction of carbon dioxide with water to form carbonic acid:
• The binding of oxygen to hemoglobin:

Gastrin, released from the lower stomach by protein, stretch and vagal signals, raises stomach acid secretion.

• It slows emptying of the stomach:
• It makes the gallbladder contract:
• Correct: It increases acid secretion by the stomach:

Carbonic anhydrase makes carbonic acid, which splits into H+ and bicarbonate. The proton pump moves H+ into the lumen against a huge gradient, Cl− follows through channels, and the two make hydrochloric acid outside the cell. Meanwhile the bicarbonate goes to the blood.

• Correct order: 1. Carbon dioxide and water combine inside the cell, sped up by carbonic anhydrase 2. Carbonic acid splits into H+ and bicarbonate 3. The H+/K+ ATPase spends ATP to pump H+ into the lumen in exchange for K+ 4. Cl− leaves the cell into the lumen through channels 5. H+ and Cl− form hydrochloric acid in the lumen of the gland

Blocking the final step of acid secretion raises the stomach's pH, so less pepsin is activated and less bicarbonate goes to the blood. The rise in pH also removes the negative feedback on gastrin, which rises.

• pH of the stomach contents: up. With the pump blocked, far less H+ is moved into the lumen, so the contents are less acidic.
• Conversion of pepsinogen to pepsin: down. Pepsinogen needs acid, below about pH 5, to cut itself into pepsin.
• Gastrin in the blood: up. Low pH normally releases somatostatin, which shuts gastrin off. Without the acid, that brake is removed and G cells keep releasing gastrin.
• Bicarbonate added to the blood by the stomach (alkaline tide): down. One bicarbonate enters the blood for each H+ secreted, so less acid means less alkaline tide.

In acid, pepsinogen changes shape and removes a short piece of itself, uncovering its active site. The pepsin formed then activates more pepsinogen, a positive feedback loop.

• Bicarbonate in the mucus layer converts pepsinogen into pepsin: Bicarbonate raises the pH, which would keep pepsinogen inactive; that is part of how the mucus layer protects the lining.
• Intrinsic factor binds pepsinogen and switches on its active site: Intrinsic factor binds vitamin B12, not pepsinogen.
• Gastrin reaches the gland lumen and cuts a piece off pepsinogen: Gastrin is a hormone released into the blood; it stimulates acid secretion but does not cut pepsinogen.
• Correct: Acid makes pepsinogen cut itself into pepsin: Correct. Acid starts the activation, and pepsin then speeds it up.

Parietal cells secrete intrinsic factor, which binds B12 in the small intestine so the lining of its last part can absorb it. Autoimmune destruction of parietal cells removes intrinsic factor, so dietary B12 passes through unabsorbed. Injections bypass the gut. This is pernicious anemia.

• Her stomach acid destroys the B12 in her food before it can be absorbed: Acid helps free B12 from food proteins; it does not destroy it. Her problem is the opposite: she has lost her parietal cells and has little acid.
• B12 in food is digested by pepsin into inactive fragments in her stomach: Pepsin frees B12 from the proteins it is bound to in food; it does not inactivate the vitamin.
• Her liver can no longer store B12, so she needs a steady supply by injection: Her liver can store B12. The problem is getting B12 across the intestinal lining.
• Correct: She lacks intrinsic factor, so she cannot absorb B12 from food: Correct. The problem is absorption, not intake, so more dietary B12 would not help.

A falling pH inhibits gastrin release: below about pH 3, D cells release somatostatin, which shuts the G cells off. This negative feedback limits acid secretion.

• Protein fragments in the stomach stimulate G cells: This step is right. Peptides and amino acids stimulate G cells directly.
• G cells release gastrin into the blood: This step is right. Gastrin is a hormone carried by the blood.
• Gastrin increases acid secretion, partly by releasing histamine: This step is right. Gastrin acts mainly through histamine-releasing cells and partly on parietal cells.
• The stomach contents become strongly acidic: This step is right. Increased acid secretion lowers the pH of the contents.
• Correct: The falling pH makes the G cells release even more gastrin: This is the error. Low pH inhibits gastrin release through somatostatin.

The small intestine sets the pace of gastric emptying. Fat arriving there is the strongest stimulus for CCK release and the enterogastric reflex, which weaken the antrum's contractions and tighten the pylorus. Carbohydrate empties fastest.

• Fat stretches the stomach more, and stretch weakens its mixing waves: Stretch of the stomach speeds emptying rather than slowing it, and equal meals stretch it similarly.
• Fat raises gastrin release, and gastrin tightens the pyloric sphincter: Gastrin is released by protein and stretch, not mainly by fat, and its effect is on acid secretion.
• Correct: Fat in the small intestine releases CCK and triggers the enterogastric reflex: Correct. Signals from the intestine, not from the stomach, hold a fatty meal back.
• Rice is absorbed through the stomach wall, so less of it remains to empty: The stomach absorbs almost no nutrients; rice leaves faster because carbohydrate triggers weaker braking signals from the intestine.

Vomit carries H+ and Cl− from the stomach. For each H+ the parietal cells secrete, a bicarbonate ion enters the blood, and when that acid is lost instead of reaching the intestine, the bicarbonate stays. The blood becomes alkaline. Potassium is lost too, so hypokalemia is common.

• Acidosis, with low bicarbonate: Bicarbonate-rich fluid is secreted further down the intestine. Vomiting mainly loses acid from the stomach.
• A rise in blood potassium: Potassium falls with repeated vomiting: it is lost in the vomit and, even more, in the urine.
• No lasting change in blood pH: The kidneys respond over hours to days and cannot fully correct the change while acid keeps being lost, especially with water loss.
• Correct: Alkalosis, with high bicarbonate: Correct. Losing stomach acid leaves extra bicarbonate in the blood.

The three stimuli amplify each other, so removing one cuts the combined effect by much more than a third. And much of gastrin's effect passes through the histamine-releasing cells, so blocking histamine also blunts gastrin.

• Histamine is the only signal that parietal cells respond to: Parietal cells respond to acetylcholine and gastrin as well; that is why a proton pump inhibitor, which blocks the final step, is even stronger.
• The drug also blocks the proton pump on the parietal cell membrane: H2 blockers act on H2 receptor proteins. The pump is blocked by a different drug class, proton pump inhibitors.
• Blocking histamine raises somatostatin release, which then blocks the pump: Somatostatin is released by low pH. An H2 blocker raises the pH, if anything reducing somatostatin.
• Correct: The three stimuli amplify each other, and gastrin acts largely via histamine: Correct. Mutual amplification, and gastrin's reliance on histamine, make histamine a strong lever.