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Home , Parietal cell

THE DIGESTIVE SYSTEM: Gastric Physiology

Dalay Olson Ph.D Office: Jackson Hall 3-120 Office hours: Friday 11-1 PM Salivary glands Oral cavity

Pharynx Lecture 1 Upper GI

Stomach Liver Lecture 2 Gastric Physiology Pancreas

Small intestine Lab #1, Lecture 3 & 4 SI, liver, pancreas and LI 3 Compare and contrast the intrinsic, paracrine, endocrine and extrinsic mechanisms of acid . Include secretion released, site of release and intended function. WAYS TO ACTIVATE CELLS IN THE GI TRACT

Extrinsic Activation: Activation of the autonomic nervous system • Parasympathetic (Vagus) SNS Vs. PSNS • Sympathetic • Extrinsic mechanisms are long reflexes Intrinsic activation: Activation of the without input from the CNS. • Mechanoreceptors and chemoreceptors activate ENS ENS activation • Intrinsic mechanisms are short reflexes Paracrine Activation: One releases a hormone that has an effect on a neighboring cell. A B • The hormone is released into the interstitial fluid and acts on a nearby cell that expresses the hormone’s receptor. Endocrine Activation: A hormone is released into the blood and has its effects on cells expressing the hormone’s receptor. ACID SECRETION C N You just saw food… S

Short Reflex Long Reflex

What happens? Your begins producing acid before the food arrives. S T How? O • Parasympathetic stimulation M • secreting cells A • secreting cells C H The release of HCl from the parietal cells relies on the involvement of extrinsic and intrinsic nerves, hormones and paracrine mediators. Mechanisms of acid secretion

• Endocrine • Paracrine • Extrinsic (LR) • Intrinsic (SR)

SR=Short Reflex LR=Long Reflex

Smith, Margaret E., and Dion G. Morton. The Digestive System: Basic Science and Clinical. Churchill Livingstone, 2010.

Protection WHAT STIMULATES ACID SECRETION?

Intrinsic and extrinsic nerves from the vagus and enteric nervous system activates HCl secretion.

Hormones (blood) Gastrin, released into the blood, acts on the parietal cells and histamine cells to ultimately increase release of HCl.

Paracrine Histamine, released in response to gastrin and vagal stimulation, activate the parietal cell to release HCl

Inhibitor of acid secretion is a hormone that is released from the stomach mucosa in response to elevated H+ levels (low pH) in the stomach. Somatostatin acts directly on the parietal cell to inhibit acid secretion. Protection ACID SECRETION: MECHANISM

Mechanism

+ - 1. CO2 from the blood is converted to H and HCO3 .

2. H+ are pumped against their gradient into the lumen of the stomach

3. HCO3- ions are moved into the blood through a Cl- exchanger.

NOTICE… 1. The blood moving through the stomach can become alkaline (alkaline tide) due to the acid production.

2. H+ are pumped against a concentration gradient…you require energy to do that… NEGATIVE FEEDBACK MECHANISM FOR ACID SECRETION Big Picture The specifics

Food in the stomach No more food in the stomach

Increases the pH Low pH due to acid secretion Activates vagus and enteric nervous system Somatostatin release to stimulate the parietal cells and the release of gastrin and histamine Inhibition of parietal cell (acid release)

Increased acid secretion and decrease Decreased acid in pH secretion and increase in pH 4 Compare and contrast with active enzymes. Explain the activation, regulation and function of . DIGESTION IN THE STOMACH

Zymogen An enzyme that is synthesized and stored intracellularly in an inactive form.

Pepsinogen A that is released by the chief cells. Its activation requires the presence of acid.

HCl cleaves pepsinogen into an active (pepsin) an inactive peptide.

Pepsin Enzyme responsible for cleaving and peptides in the stomach.

Responsible for ~20% of total digestion. 5 Describe the and . Explain how and acid help with and iron absorption. Protection MUCUS SECRETION

Characteristics Sticky and thick 80% carbohydrate chains Alkaline High [bicarbonate]

Function Lubricates the food Protects against acidic stomach acid

Prostaglandins play a critical role in maintaining mucosal integrity, bicarbonate secretion and mucin production.

What drugs inhibit prostaglandin synthesis? INTRINSIC FACTOR AND IRON ABSORPTION

Intrinsic Factor • Only substance secreted by the stomach that is essential to life. • Large 55,000 kDa glycoprotein that complexes with vitamin B12. • Normally B12 is inefficiently absorbed, but when complexed it can be absorbed in the distal part of the intestine.

Iron Absorption • Iron is absorbed in the body as ferrous ion (Fe2+). • Under basic conditions Fe2+ can become oxidized to Fe3+ a form of iron that is not well absorbed. • The acidic environment helps prepare the iron for absorption in the intestine • People taking chronic antacids or proton pump inhibitors can suffer from iron malabsorption. MILLIONS OF AMERICANS TAKE PROTON PUMP INHIBITORS.

WHAT ARE THE DOWNSIDES?

Think about…

Clostridium difficile infection

Iron Absorption

Pepsinogen activation