Lesson 62: Stomach Function, Emesis, Mucosal Barrier and GI Motility

ENTERIC NS = Brain of the Gut

Contains as many neurons as the spinal cord

Between esophagus and anus

Consists of a myenteric and a mucosal plexus

Both are local (short) reflex systems with sensory receptors, sensory & motor fibers, cell bodies and effectors

Myenteric Plexus

between circular and longitudinal muscle layer

its mechanoreceptors respond to stretch = distension of the gut wall = presence of food

its effectors are smooth muscle cells ➔ controls GI motility

Anatomy of the myenteric plexus

Submucosal Plexus:

between mucosa and muscle layer

its chemoreceptors respond to ingesta composition: pH, fat content, protein content

effectors are mucus cells, secretory cells ➔ Controls secretion rates of fluids, bicarb and mucus

The ENS uses a multitude of neurotransmitters

Excitatory, such as serotonin, substance P, motilin, acetylcholine

Inhibitory, such as vasoactive intestinal peptide (VIP), nitric oxide, dopamine, opioids, NE etc

very responsive system to many endogenous compounds, bacterial products and drugs

Sympathetic GIT main effects

Decreases GIT motility (beta-2, alpha-2)

Decreases GIT secretion rates (alpha-2)

Decreases blood flow to the GIT (alpha-1)

Stimulates GIT sphincters (alpha-1)

Enteric NS (local reflexes) and the Autonomic NS (central reflexes) are stimulated by and share the same?

chemoreceptors and mechanoreceptors and work in tandem

The strongest stimulator for both is GI wall distension

Enteric Immune System:

Composed of mesenteric lymphnodes, gut-associated lymphoid tissue (GALT), Peyers patches, mucosal WBCs

Function of the enteric immune system

If challenged, release pro-inflammatory cytokines

Cytokines act as local stimulators of the ENS and greatly stimulates GI motility and secretions

PERISTALTIC RUSH to flush out pathogens

GI smooth muscle: Peristaltic Contractions

travel long distances via coordinated local (ENS) reflexes: contractions cranial to a bolus with relaxation caudal to it → push ingesta slowly along the GI tube

GI smooth muscle: Mixing / Segmentation Contractions

travel short distances; circular muscle contractions mostly ENS generated → squeeze ingesta and move it back and forth

Interstitial cells of Cajal

Upon stimulation by a priming factor such as stretch, a motor ENS or ANS neuron

releases acetylcholine at a motor junction, which depolarizes the muscle membrane

further and pushes the top of slow waves above threshold potential → initiates action

potentials → muscle contraction.

Storage occurs in the proximal stomach = Fundus, facilitated via the Accommodation Reflex:

Food enters stomach ➔ distention stimulates stretch receptors ➔ sensory signals ascend via vagus nerve to medulla / vagal nuclei ➔ motor signals descend via vagal motor fibers to stomach muscles ➔ release of inhibitory NTs(nitric oxide) ➔ relaxation of muscles in proximal stomach ➔ enables expansion without pressure increase

Accommodation champions: Carnivores

can accommodate up to 25% of their body weight in the proximal stomach.

Purpose: “Feast-fasting” feeding pattern, regurgitation feeding of young

MIXING, GRINDING & RELEASE (Body & Antrum): Induction

Pacemaker area induces rhythmic slow waves traveling towards the pylorus, e.g. 3 waves/min

Stomach wall distension during feeding stimulates the ENS, ANS and endocrine cells, pushing slow waves above threshold and causing up to 3 strong peristaltic waves/min

Mixing, grinding, & release: Process

Contractions towards antrum → small volumes of fluid chyme pass into duodenum before the pylorus contracts ahead of a wave → most of the content is squirted back(=retropulsion) → repeat cycle

Content is kneaded for several hours, involving more of the stored ingesta as fluid chyme is released into the small intestines.

Stomach retention time of solid food: 4-12 hours /dog.

Motility pattern during fasting

Involves a powerful persitaltic wave action(5-10 minutes) sweeping from the stomach, along the small intestines into the large intestines („ stomach rumbling“).

Clears stomach and SI of residual ingesta, Avoids bacterial overgrowth in the SI.

Stimulated largely by the hormone Motilin, released from endocrine M-cells in the antrum and duodenum in the absence of food

Parietal cells produce hydrochloric acid

Pure HCl solution has a pH of <1

Mixed with stomach content: pH 1-2 in carnivores; pH 3-4 in omnivores

Production of HCL

active H+ / K+ pump = Proton Pump

it pumps H+ into the stomach lumen in exchange against K+ → Cl- follows down an electrical gradient

Functions of HCL

Bactericidal

Denatures dietary proteins

Activates gastric pepsinogen to pepsin

Emulsifies dietary fat into smaller globules

Triple control of HCL secretion

Somatostatin

released from endocrine D cells when the stomach pH is too low = negative feedback → inhibits proton pump, gastrin and histamin release

Intrinsic Factor is co-secreted with HCl

Binds to Vit B12(cobalamin) and protects it from being digested by pancreatic proteases

Both are absorbed in the ileum via a specific transporter.

Vit B12 is a necessary cofactor for DNA replication / mitosis.

Lack of Intrinsic Factor / Vit B12 deficiency affects:

RBC production / anemia

Nerve function / demyelination

Normal body growth

Most animals produce Intrinsic Factor mostly in the pancreas

pancreatic dysfunction can lead to Cobalamin deficiency in dogs, cats, horses

A genetic lack of IF-absorption mechanism exists in Giant Schnauzers

Chief cells produce Pepsinogens

HCL activates the proenzyme pepsinogens to the active pepsins

Pepsins’ pH optimum lies between pH 1-3.

Pepsins are proteolytic enzymes and hydrolyze large polypeptides into smaller polypeptides and oligopeptides

Chief cells co-produce gastric lipases

Hydrolyse some triglycerides; minor overall importance

Control of pepsinogen secretion:

Central & local reflexes (acetylcholine)

Gastrin

Carbohydrate digestion

salivary amylase hydrolyzes polysaccharides (typically 1000s of Glc) into a mixture of smaller polysaccharides and oligosaccharides (3-20 Glc).

10-30% of carbohydrate digestion occurs in the stomach

Amylase is destroyed once exposed to HCl (works only in the accommodation phase)

Protein digestion

HCl: denatures proteins = breaks up 2-3-4 structures into primary polypeptide chains.

Pepsin: Enzymatic hydrolysis of primary polypeptide chains to a mixture of smaller

polypeptides, oligopeptides and some amino acids

10-20% of protein digestion occurs in the stomach

Fat digestion

HCl: Begins the emulsification process = dividing larger into smaller fat globules.

Lingual & Gastric Lipases: Some hydrolysis of triglycerides into monoglycerides and free fatty acids (less than 5% of fat digestion) → More important in neonates for milk fat digestion.

Causes of vomiting

Peripheral signals from the GIT, pancreas, liver, peritoneum: Distension!! Inflammation, Irritation, Toxins, Foreign bodies

Chemical signals: endotoxins, exotoxins, waste products (ammonia, urea, ketone bodies, lactic acid, CO2), some hormones (hCG)

Vestibular Signals: motion sickness, vestibular disease

Higher CNS: pain, fear, stress, olfactory & gustatory signals

Prodromal Phase of vomiting(Nausea)

Drooling, lip licking, frequent swallowing, isolation

Retching (Dry Heaves)

Rhythmic abdominal contractions; SI antiperistaltic waves push ingesta back into the stomach; pylorus closes & cardia opens; expulsion of ingesta into esophagus

Expulsion (Vomiting)

Epiglottis closes; diaphragm and abdominal muscles contract powerfully; ingesta is pushed out via mouth, sometimes nose

Blood-borne signals activate the Chemoreceptor Trigger Zone (CTZ)

Its chemoreceptors detect and bind to a multitude of chemicals: toxins, waste products →

stimulating the CTZ neurons → transmit signals to the Vomiting Center to induce vomiting

Location of the CTZ

sits in the 4th ventricle above the medulla, outside of the blood-brain-barrier(BBB) → has direct access to circulating emetogenic substances

The Vomiting Center and the CTZ can be activated via many different causes and carry multiple receptors → drug targets:

Consequences of vomiting

Dehydration

Hypokalemia → hyperpolarization of excitable cells → nerve & muscle weakness

Alkalosis (or acidosis if small intestinal content is expulsed)

Esophagitis / aspiration pneumonia

Regurgitation

passive expulsion of ingesta from the esophagus or forestomach

No nausea , no abdominal contractions → Controlled by local reflexes in the esophagus

Reverse peristalsis pushes undigested food back into the mouth

Causes of regurgitation

Esophagitis

Megaesophagus (myesthenia gravis)

Esophageal stricure (RPAA; parasites)