Physiology digestion

Explain the steps of HCI production

1.     Intracellular Generation of H⁺ and HCO₃⁻:

• CO₂ + H₂O → H₂CO₃

  • Catalysed by carbonic anhydrase (CA) inside the parietal cell.

• H₂CO₃ → H⁺ + HCO₃⁻

  • Carbonic acid dissociates into a proton (H⁺) and bicarbonate (HCO₃⁻).

2.     Secretion of H⁺ into the Stomach Lumen:

• H⁺/K⁺-ATPase (“proton pump”)

• Located in the apical (luminal) membrane of the parietal cell.

• Primary active transport: uses ATP to exchange one intracellular H⁺ for one extracellular K⁺.

• Pumps H⁺ into the gastric lumen against a very steep gradient.

3.     Recycling of K⁺ and Cl⁻ Entry:

• K⁺ recycle

  • The K⁺ brought in by the pump leaks back into the lumen through apical K⁺ channels, keeping luminal K⁺ available for the pump.

• Cl⁻ influx

  • On the basolateral (blood) side, Cl⁻ enters the cell mainly via a secondary active transporter (the HCO₃⁻/Cl⁻ exchanger): as HCO₃⁻ exits into the blood, Cl⁻ moves in.

4.     Secretion of Cl⁻ into the Lumen:

• Facilitated diffusion

  • Cl⁻ exits the parietal cell into the stomach lumen through apical Cl⁻ channels.

• Result in lumen: H⁺ + Cl⁻ → HCl, contributing to the highly acidic gastric juice (pH ~1–2).

5.     The “Alkaline Tide” in the Blood

• As HCO₃⁻ is generated and then pumped out of the cell on the basolateral side in exchange for Cl⁻, the venous blood leaving the stomach becomes transiently more alkaline.

What are the main components of digestion in the GI tract?

Mechanical grinding of food, secretion of juices (enzymes/detergents), breakdown of nutrients, and motor function (motility)

What other functions does the GI tract perform besides digestion?

Absorption, excretion, endocrine functions, and protective functions

What reaction generates H⁺ and HCO₃⁻ inside parietal cells?

CO₂ + H₂O → H₂CO₃, catalyzed by carbonic anhydrase, followed by H₂CO₃ → H⁺ + HCO₃⁻

Which enzyme catalyzes formation of carbonic acid in parietal cells?

Carbonic anhydrase

How are protons secreted into the stomach lumen?

By the H⁺/K⁺-ATPase (“proton pump”) in the apical membrane, exchanging intracellular H⁺ for extracellular K⁺ using ATP (primary active transport)

How is luminal K⁺ recycled in parietal cells?

K⁺ brought in by the pump leaks back into the lumen through apical K⁺ channels, keeping luminal K⁺ available for the pump

How does Cl⁻ enter parietal cells?

Via a basolateral HCO₃⁻/Cl⁻ exchanger: as HCO₃⁻ exits into the blood, Cl⁻ moves into the cell by secondary active transport

How is Cl⁻ secreted into the gastric lumen?

Through apical Cl⁻ channels by facilitated diffusion

What combines in the lumen to form HCl?

Secreted H⁺ and Cl⁻ combine to form hydrochloric acid, giving gastric juice a pH of about 1–2

What is the “alkaline tide”?

A transient rise in pH of venous blood leaving the stomach due to HCO₃⁻ being pumped into the blood by parietal cells

Which neurotransmitter stimulates HCl secretion via M-cholinoreceptors?

Acetylcholine

Which hormone from gastric endocrine cells stimulates HCl secretion?

Gastrin

How do acetylcholine and gastrin activate the proton pump?

They bind receptors that trigger IP₃/DAG pathways, raise intracellular Ca²⁺, activate protein kinases, and thus activate the H⁺/K⁺ pump

How does gastrin indirectly enhance HCl secretion?

By stimulating histamine release from enterochromaffin-like (ECL) cells

What role does histamine play in acid secretion?

It binds H₂ receptors, activates Gs protein and adenylate cyclase, increases cAMP, activates protein kinases, and stimulates the H⁺/K⁺ pump

How do prostaglandins inhibit HCl secretion?

PGE₂ acts via Gi protein to inhibit adenylate cyclase, reduce cAMP, inactivate protein kinases, and inhibit the H⁺/K⁺ pump

How does somatostatin inhibit HCl secretion?

It directly inhibits adenylate cyclase in parietal cells, reduces H⁺/K⁺ pump activity, and indirectly suppresses gastrin and histamine release

What triggers the cephalic phase of gastric secretion?

Sight, smell, thought of food, and food in the mouth, via vagal stimulation

What initiates the gastric phase of secretion?

Food in the stomach stretches the mucosa and chemical stimuli activate local reflexes within the stomach wall and increase gastrin release (unless HCl is excessive)

What characterizes the intestinal phase of gastric secretion?

Fats, carbohydrates, and acid in the duodenum inhibit secretion via neural and humoral mediators (secretin, CCK, PYY, GIP)

What is receptive relaxation?

A vagally mediated relaxation of stomach muscles during swallowing that accommodates incoming food with minimal pressure increase

What types of gastric contractions exist?

Peristaltic, pyloric (systolic), slow changes of muscle tone, antiperistaltic, and hunger contractions

How is gastric emptying controlled?

By the strength of antral contractions and the tone of the pyloric sphincter regulating passage into the duodenum

How does parasympathetic activity affect gastric motility and emptying?

Acetylcholine via M₃ receptors increases antral contractions and pyloric tone (braking emptying)

What is the effect of sympathetic stimulation on gastric motility?

It weakly inhibits both motility and gastric emptying

How do gastric factors influence emptying?

Stomach wall stretch increases motility

What is the enterogastric reflex?

Neural inhibition of gastric motility and emptying triggered by duodenal distension, hyperosmolarity, protein digestion products, acid, or mucosal irritation, plus CCK, GIP, and secretin release

What stimuli activate the vomiting center?

Irritation of upper GI mucosa, circulating chemicals at the area postrema, and equilibrium (vestibular) inputs

What events occur during vomiting?

Reverse peristalsis moves intestinal contents into stomach, abdominal muscles contract to raise intra-abdominal pressure, and the lower esophageal sphincter relaxes to eject contents

What stimulates pancreatic enzyme secretion?

Acetylcholine from parasympathetic nerve endings

Which hormones regulate pancreatic secretion?

CCK stimulates acinar enzyme secretion in response to fats and proteins

What are the main functions of the liver?

Bile formation, glycogen storage, ammonia detoxification to urea, plasma protein synthesis, metabolism of amino acids/fats/hormones/cholesterol, drug/toxin detoxification, blood reservoir (~15%), and iron storage

What increases bile production by the liver?

Vagal stimulation, secretin (↑ water and HCO₃⁻ in bile), and elevated blood bile salts stimulating hepatocytes

What causes gallbladder contraction?

CCK release in response to duodenal fatty acids and amino acids, and weak vagal stimulation

How is the sphincter of Oddi relaxed?

By CCK and by relaxation waves during duodenal and gallbladder contractions

What does the myenteric (Auerbach) plexus control?

It increases intestinal wall tone, and the intensity and rate of rhythmic contractions

What does the submucosal (Meissner) plexus control?

Local secretion, absorption, and contraction of submucosal muscles within each intestinal segment

How do autonomic nerves interact with the enteric plexuses?

Parasympathetic input increases peristalsis

What stimulates peristalsis after a meal?

Entry of chyme into the duodenum and the gastro-enteric reflex from stomach distension via the myenteric plexus

Which humoral factors inhibit intestinal peristalsis?

Secretin and glucagon

Which humoral factors enhance intestinal peristalsis?

Gastrin, CCK, insulin, and serotonin

Why are dietary fibers important for intestinal function?

They add bulk to the stool, promoting frequent movements

What initiates the intrinsic defecation reflex?

Rectal distension by feces at ≥18 mmHg triggers weak peristaltic waves and internal anal sphincter relaxation via the myenteric plexus

How does the parasympathetic defecation reflex reinforce defecation?

Stretch-receptor signals to the sacral spinal cord return efferents that contract the colon, sigmoid, rectum, and relax the internal sphincter, producing a strong defecation response

What is required for voluntary defecation?

Relaxation of the external anal sphincter (or reaching ≥55 mmHg pressure), plus straining with glottis closure and abdominal wall contraction to increase intra-abdominal pressure