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Regulation of GI System

Enteric nervous system reflexes

Sympa and Para input

Hormones

Paracrine signals

Short-loop reflexes

Only involves enteric nervous system

Long-loop reflexes

CNS and autonomic input to enteric nervous system

Digestion occurs in three phases

Cephalic phase

Gastric phase

Intestinal phase

Substrate phase (metabolism/fed state)

Cephalic Phase

Digestion before food enters mouth

Thinking, seeing, smelling food, prepare body for digestion

Feed-forward

Salivary secretions

Enhanced by presence of food in mouth

Starts digestion

Contains amylase, lysozyme, salivary lipase, and mucins

Chewing begins mechanical breakdown

Beginning of gastric secretions

All long-loop reflexes involving the brain and para

Swallowing

Prepare stomach to receive chyme

Inc vagal nerve activity to stomach

Promotes gastric acid secretion from parietal cells

Promotes pepsinogen secretion from chief cells

Gastric phase

Food entering stomach starts this

Gastric motility and secretions initiated during cephalic continue

Stretch to stomach wall

Presence of peptides and inc pH in stomach (bc buffer also sensed by stomach lining) signals this too

Both short and long loop reflexes

Also gastrin released by stomach

Major Gastric Secretions

HCl by parietal cells of stomach

H K ATPase on lumenal membrane

1-3 L HCl secreted a day to lower pH to 1.5

Parietal cells also secrete INTRINSIC FACTOR (PROTEIN TO ABSORB VITAMIN B12)

Chief cells secrete pepsinogen that gets converted to pepsin by stomach acid

Mucus/neck cells secrete mucus

Gastrin is secreted into blood, stimulated by vagal input to G cells

Hormone

BLOOD NOT DIGESTIVE TRACT

Amino acids and peptides in lumen of stomach cause secretion

Short loop control

Stimulates parietal cells to release acid

Acts directly on parietal cells to release Histamine which also acts on parietal cells to stimulate acid secretion (histamine released by enterochromaffin cells)

Enterochromaffin cells stimulated by enteric nervous system

Acid inhibits gastrin release

Neg feedback

Mediated by prostaglandin in PGE2

Pepsinogen

Secreted bc of acid in stomach

Somatostatin (GHIH)

Secreted bc of acid in stomach

Secreted by D cells (D cells found in pancreas, intestine, and stomach)

Negative feedback regulator of gastrin, acid, and pepsinogen

Key role of stomach is to:

Start protein breakdown

Acid and pepsin

Mechanical breakdown of food

Acid in stomach destroys salivary enzymes

Lipid soluble molecules can be directly absorbed through stomach wall

Stomach is one organ but has 3 regions

Fundus

Top portion

Receives and stores chyme

Body

Middle

Secretes mucus, acid, pepsinogen

Continues starch breakdown

Antrum

Distal third

Secretes mucus, acid, pepsinogen

Mixing is complete enough so protein digestion is the main action

Stomach motility

Empty stomach volume 50 ml

During empty stomach phase lower esophageal sphincter closed and pyloric sphincter is NOT tightly closed

In contrast when swallowing lower esophageal sphincter is not tightly closed but pyloric sphincter is

Mixing contractions 3/min ; frequency is intrinsic property of stomach muscles, but strength is innervated neural and hormonally

Filling of stomach causes contraction pushing chyme through pyloric sphincter

The Intestinal Phase

Delivery of chyme to small intestine

Acid chyme in duodenum causes secretin release

Hormone secreted into blood NOT intestine

Inhibits acid secretion and gastric motility

Stimulates bicarbonate secretion from pancreas (acid neutralization)

Fat in duodenum stimulates cholecystokinin (CCK) secretion

Inhibits gastric acid secretion and motility

Most digestion and absorption occurs in small intestine

Small Intestine Secretions

Bicarbonate: Secreted mostly from pancreas in response to secretin

Also neural inputs

Neutralizes gastric acid

Pancreatic Enzymes

Secreted in response to neural signals (stretch receptors and hormones)

In response to CCK (signals chyme is in intestine)

Bile: Secreted from liver

Contains bile salts, pigments, and cholesterol

Made by liver stored in gall bladder

Gall bladder contracts in response to CCK to secrete bile and break down fats

Mucus: Goblet cells in small intestine

Glucose-dependent insulinotropic hormone (GIP)

Released when chyme is present

Causes insulin secretion from pancreas

Feed forward (prepare body for incoming glucose)

Neg feed back (turning of gastric phase)

Glucagon-like peptide (GLP)

Released by intestines

In response to nutrients and stretch

Stimulates pancreas insulin secretion

Gastric ulcers and Gastric Acid

Gastric acid can eat a hole in the lining of the intestines/esophagus if it can make it there

Surface is protected by mucus; if mucus wasn’t there or too much acid, lining would ulcerate

Helicobacter pylori; breaks down mucus lining

Excess acid secretion treated by:

Proton pump inhibitors (esomeprazole)

Histamine antagonists (tagamet)

Different than histamine antagonists for allergies (diff histamine receptors)]

Gut Microbiome

More bacteria in gut than cells in body

Composed of bacteria from two major phyla: Bacteroidetes and Firmicutes

1000 diff types bacteria species most anaerobic

Important for nutrient and drug metabolism, maintenance of mucosa, and immune system

Composition of biome varies with diet and drug intake and also birthing method, and diet as an infant

Metabolism Overview

Body needs constant substrates for energy, step after nutrients have been absorbed

Absorptive state (fed state)

During digestion of a meal nutrients and energy are in abundance

Post absorptive state (fasted)

Between meals

After absorption occurs

Body makes use of stored energy accumulated during fed state

Takes 4 hours to fully digest a meal

3 meal a day pattern of food intake

Post absorptive during late morning, late afternoon, and all night

Half each day spent in each phase

Three types of nutrients for energy

Carbs

Absorbed as free sugars (glucose mainly, galactose converted to glucose by liver)

Enter hepatic portal circulation

Fats

Absorbed as chylomicrons

Absorbed through lacteals in lymphatic system which delivers them into blood stream at vena cava

Proteins

Absorbed as amino acids

Enter hepatic portal circulation

Meals contain mixture of all these nutrients

Glucose preferred energy source

Sugar in abundant supply in absorptive phase

What gets metabolized for energy

Some gets stored

Glucose storage during absorptive state

Glycogen: mainly in muscle

Muscle is a large amt of tissue mass; cell type that always needs energy

Liver makes and stores some glycogen

Liver converts glucose to triglycerides (glycerol phosphate fatty acid)

Complexes triglycerides with proteins to form lipoprotein complex VLDL which are released into blood

VLDL broken down by lipoprotein lipase (enzyme in capillaries in fat)

Liberated fatty acids made in liver stored in fat cells adipocytes

Glucose also used by adipocytes to form glycerol phosphate and fatty acids--> stored as triglycerides

Amino Acids in Absorptive State

Get taken up by cells for new protein synthesis

Metabolized by keto-acids that get metabolized for energy or converted to fatty acids

Fats in the Absorptive State

Triglycerides in chylomicrons handled same way as VLDL from liver

Post Absorptive State

When absorptive state is over glucose no longer entering circulation from GI tract

Needs to be supplied from storage

Characterized by glucose production:

Glycogenolysis: breakdown of glycogen

Lipolysis: break down of lipids

Gluconeogenesis: synthesis of glucose from smaller carbon chain molecules

Endocrine and Neural Switching Between States

Hormones

Insulin and Glucagon

Secreted by Islets of Langerhans (>1% cells in pancreas; most exocrine)

Beta cells secrete insulin (70% cells)

Alpha cells secrete glucagon (20% cells)

Insulin primary hormone of absorptive state

Glucose uptake

Glucose storage

Amino acid uptake and protein synthesis

Insulin

Stimulates glucose uptake in cells

Stimulates uptake of glucose in muscle cells and glycogen storage

Stimulates amino acid uptake and them being made into proteins

Stimulates glucose uptake and synthesis of triglycerides in fat cells

Glucose uptake , synthesis of glycogen, and triglycerides in liver

Inc glucose uptake by inserting glucose transporters into cell membrane and altering enzyme activity

Insulin secretion controlled by plasma glucose level

Detected by beta cells

Inc glucose inc insulin

GIP released from intestines feed forward for insulin

Other hormones (incretins)

Diabetes Mellitus

Insulin deficiency(I) or dec response to it(II)

Type I

10% affeced

Juvenile

Most severe: destruction of insulin-secreting cells of pancreas

Type II

90%

Adults w obesity

Blood glucose inc very high in absorptive state

Symptoms

Loss of vision

Renal disease

Inadequate blood flow to feet; high levels glucose cause glycosylation of proteins which causes damage to microvasculature

A1c: lowering degree glycosylation of A1c subunit of hemoglobin; used as index for protein glycosylation--> shows if high levels of glucose are present

Glucagon

Insulin plays primary role in controlling metabolic state

Counter regulatory control

Acts on liver to reverse effects of insulin

Dec in glucose levels stimulates release

Inc of plasma amino acid levels in absence of inc glucose

Sympa nerves