Lecture Notes on Stomach Functions & Control

Course Information

  • Course: VM520

  • Module: GIT, Metabolism & Nutrition

  • Lesson 69: Stomach Functions & Control

  • Instructor: Dr. Ulrike Zieger

  • Semester: F25

Learning Outcomes

GIT 69 Intended Learning Outcomes (ILOs)

  • Importance of understanding the physiological and pathological terms related to the GIT.

  • Video content: Chemical breakdown of nutrients in the GIT.

  • Students should be able to describe:

    • How gastrointestinal (GI) functions are controlled.

    • The secretory functions of the stomach.

    • The motility functions of the stomach.

    • The concept of the GI mucosal barrier.

    • Causes and consequences of damaging the mucosal barrier.

    • The process, causes, and consequences of emesis (vomiting) and regurgitation.

Prework Questions

Prework Question TPS

  • Question: What are the final products when a triglyceride is hydrolyzed by digestive enzymes?

  • Answer:

    • Free Fatty Acids

    • Glycerol

Structure of Salivary Glands / GIT 69: Gastric Phase Overview

Control Mechanisms

  • Enteric and Autonomic Nervous System

  • Endocrine and Immune System

Mechanical Digestion

  • Motility Pattern

    • Storage of food in the proximal stomach.

    • Grinding, mixing, and release of chyme in the distal stomach.

    • Motility pattern during the resting phase.

Chemical Digestion

  • Involves stomach secretions during the initial digestive steps.

Protective Functions

  • Gastrointestinal Barrier

  • Emesis and Regurgitation

Overview of Control Mechanisms

What Needs to Be Controlled?

  • Motility: Involves mechanical digestion.

  • Secretions: Involves chemical digestion.

Purpose

  • To adjust stomach functions according to the incoming quantity and quality of food.

Who Controls These Functions?

  • Enteric Nervous System (ENS)

  • Autonomic Nervous System (ANS)

  • Endocrine System

  • Immune System

Enteric Nervous System (ENS)

Overview

  • The gut wall contains a complete nervous system which is referred to as the ENS or the "Brain of the Gut".

    • Found in smooth muscles between the esophagus and anus.

    • Composed of:

    • Myenteric Plexus: Controls GI motility.

    • Mucosal Plexus: Controls GI secretions.

Reflex Arcs

  • The ENS contains simple reflex arcs with receptors, sensory and motor fibers, cell bodies, and effectors that control GI motility and secretions via local (short) reflexes, independently of the ANS.

Main Signals

  • GI wall distension → Myenteric mechanoreceptors → Increased GI motility.

  • Mucosal chemoreceptors → Increased GI secretion rates.

Neurotransmitters in the ENS

  • The ENS releases various neurotransmitters including:

    • Acetylcholine (mostly excitatory)

    • Norepinephrine (mostly inhibitory)

    • Serotonin

    • Dopamine

    • Cholecystokinin (CCK)

    • ATP

    • Somatostatin

    • Motilin

    • Substance P

    • Vasoactive Intestinal Peptide (VIP)

    • Opioids

Autonomic Nervous System (ANS)

Parasympathetic System

  • Supplied by the Vagus Nerve (CN X) and Pelvic Nerves.

    • Contains sensory fibers from GI chemoreceptors and mechanoreceptors that send signals to the medulla.

    • From the medulla, motor fibers innervate GI muscles, gland cells, mucus cells, and endocrine cells.

Main Neurotransmitter

  • Acetylcholine at nicotinic receptors.

Main Stimuli

  • GI wall distension and nutrient density, leading to:

    • Increased GI motility (mostly)

    • Increased GI secretion rates

    • Relaxation of GI sphincters, facilitating digestion.

Sympathetic System

  • Originates from the thoracolumbar chain (T5-L2).

    • Nerve fibers pass through mesenteric ganglia into the GI wall.

    • Contains sensory and motor fibers.

Main Neurotransmitter

  • Norepinephrine.

Main Signals

  • GI wall distension and nutrients lead to:

    • Decreased GIT motility

    • Decreased GIT secretion rates

    • Decreased blood flow to the GIT

    • Stimulation of GIT sphincters, thus slowing down digestion.

Note

  • ENS and ANS are stimulated by the same chemoreceptors and mechanoreceptors, working in tandem for efficient control.

Endocrine Control

Endocrine Cells

  • Located throughout the GI mucosa and monitor incoming chyme via chemoreceptors located on microvilli that extend into the gut lumen.

  • When stimulated by appropriate stimuli (e.g. proteins), they release hormones:

    • Into the bloodstream = endo-crines.

    • Into the interstitium = paracrines.

Hormonal Influence

  • Hormones released influence motility and secretion rates of the GI tract, including those of the pancreas and liver.

    • Approximately 35 regulatory peptides are identified to date, including:

    • Gastrin

    • Somatostatin

    • Secretin

    • Cholecystokinin (CCK)

    • Gastric Inhibitory Peptide

    • Motilin

    • Enteroglucagon

    • Peptide YY

Insight

  • Many of these are also neurotransmitters, showing the neuro-endocrine connection in the GI system.

Immune System

Enteric Immune System Components

  • Composed of:

    • Mesenteric lymph nodes

    • Gut-associated lymphoid tissue (GALT)

    • Peyers patches

    • Mucosal White Blood Cells (WBCs)

Immune Response

  • Upon challenge, these components release pro-inflammatory cytokines which act as local paracrines, stimulating GI motility and secretions to flush out pathogens.

Protective Mechanism

  • The response is termed Peristaltic Rush, a strong increase in motility and secretion designed to protect the organism from pathogens commonly entering through the oral pathway.

Clinical Considerations

  • Signs of peristaltic rush include diarrhea, bloating, pain, and cramping.

  • Clinical management should focus on observing the patient.

    • Treatment consideration should be based on duration and severity of symptoms.

Mechanical Digestion

Motility Pattern

Overview

  • The smooth muscles of the GIT contain self-excitatory pacemakers known as the Cells of Cajal:

    • These cells generate rhythmic changes in membrane potential called slow waves.

    • Slow wave potential range: -60/-50 mV

    • Frequency: 3-12 waves/min

    • Waves travel a few centimeters.

Activation of Contractions

  • Slow waves are not contractions.

  • Contraction occurs when a slow wave reaches threshold potential at around -40/-35 mV, causing Ca channel opening, leading to:

    • Rapid influx of calcium ions which initiates smooth muscle contractions (action potential).

Factors Influencing Contraction

  • Priming factors include gut wall distention, parasympathetic stimulation, and certain hormones that can increase motility from 0 to 12 contractions/min.

Stomach Accommodation Reflex

Mechanism

  • The accommodation reflex facilitates the storage function of the stomach:

    1. Food enters the stomach triggering distention.

    2. Mechanoreceptors stimulated send sensory signals to the medulla via vagus nerve.

    3. Motor signals descend back to stomach muscles releasing inhibitory neurotransmitters (e.g., nitric oxide).

    4. Resulting in relaxation of muscles in the proximal stomach, allowing expansion without increasing pressure.

Importance

  • This process allows large volumes of food to be swallowed and stored temporarily while mixing with gastric juices before being passed on to the duodenum.

  • Disruption of the reflex (e.g., due to strong sympathetic stimulation) can impair accommodation and increase intragastric pressure, leading to sensations of fullness or discomfort.

Accommodation Capacity

  • Different species have varying accommodation capabilities:

    • Carnivores: Can accommodate up to 25% of body weight in the proximal stomach.

    • Pythons: Can expand stomach volume up to 10 times.

Migrating Motility Complex (MMC)

Overview

  • During fasting, the MMC occurs approximately every 2 hours involving a cyclic pattern of powerful peristaltic wave action that moves contents from the stomach through the small intestine into the large intestine.

    • This process helps clear residual food and secretions and prevents bacterial overgrowth in the small intestine.

    • Primarily stimulated by the hormone Motilin, released from M-cells in the antrum and duodenum.

Chemical Digestion

Hydrochloric Acid (HCl)

Production

  • HCl is produced by parietal cells through an active H+/K+ pump:

    • Pumps H+ into the stomach lumen in exchange for K+, with Cl- following down an electrical gradient, resulting in a solution with a very low pH (<1).

    • Mixed with stomach contents, yields pH levels ranging:

    • pH 1-2 in carnivores

    • pH 3-4 in omnivores

Functions

  • HCl performs several key functions:

    • Bactericidal action

    • Denaturing proteins

    • Activating pepsinogen to pepsin

    • Emulsifying fats

Regulation of HCl Secretion

  • Acetylcholine via ANS and ENS reflexes upon food arrival.

  • Gastrin released by G cells in response to dietary proteins.

  • Histamine: Gastrin stimulates ECL cells to release histamine, which is the strongest HCl stimulator through parietal cell H2 receptors.

  • Somatostatin: Released from D cells when stomach pH drops too low, inhibiting proton pumps and gastrin/histamine release.

Intrinsic Factor

  • Co-secreted with HCl and plays a crucial role in binding Vitamin B12, protecting it from digestion.

    • Both intrinsic factor and Vitamin B12 are absorbed in the ileum.

    • A deficiency in intrinsic factor can lead to problems including anemia and nerve function impairments.

Pepsinogen

  • Chief cells produce pepsinogen which is activated to pepsin in acidic environments (pH 1-3).

    • Pepsins are proteolytic enzymes that hydrolyze large polypeptides into smaller polypeptides and oligopeptides.

    • In addition, chief cells co-produce gastric lipases, which have minor importance in hydrolyzing triglycerides.

Nutrient Breakdown in the Stomach

  • Carbohydrates:

    • Salivary amylase initiates hydrolysis of polysaccharides into smaller units (noted as <30% of carb digestion) before being inactivated by HCl.

  • Proteins:

    • Denaturation by HCl followed by hydrolysis by pepsin leading to smaller polypeptides (10-20% breakdown).

  • Fats:

    • Initial emulsification occurs with HCl breaking larger fat globules into smaller ones; minimal hydrolysis of triglycerides via lingual and gastric lipases (<10% fat digestion).

Protective Function / Gastrointestinal Barrier Components

The GI Dilemma

  • The gastrointestinal tract must protect itself from:

    • Acid and digestive enzymes

    • Invading pathogens

  • Nonetheless, it must permit nutrient absorption.

Barrier Composition

  1. Physical Barrier:

    • Mucus: Covers the stomach surface and intestinal mucus cells, rich in bicarbonate, protecting against acid and mechanical damage.

    • Tight junctions between epithelial cells limit permeability.

  2. Chemical Barrier:

    • Prostaglandins stimulating mucus, bicarbonate production, and vasodilation; reduces HCl production.

  3. Immunological Barrier:

    • GALT, Peyers patches, and lymphoid tissues containing immune cells such as macrophages, T- and B-cells.

    • Secretory IgAs neutralize pathogens in the GI lumen.

  4. Microbiological Barrier:

    • Healthy gut flora competes with pathogens and can produce anti-microbials.

  5. Healing Capacity:

    • Rapid turnover and replacement of damaged cells supported by stem cells throughout the intestinal mucosa.

Disruption of the GI Barrier

  • Factors leading to disruption:

    • Stress, cortisol, NSAIDs, infections (like H. pylori), ill-perfusion, dysbiosis.

    • Consequences include acute/chronic gastritis, erosions, ulcerations, etc.

Example: Equine Gastric Ulcer Syndrome (EGUS)

  • High prevalence in performance horses, with incidence rates up to 90%.

Causes

  • Fasting or infrequent feeding, high grain/low fiber diets, intense exercise, stress, NSAID usage.

Emesis (Vomiting)

Definition

  • Vomiting is the forceful expulsion of GI content via the mouth triggered by the vomiting reflex.

Causes

  • Peripheral Signals:

    • From GIT, pancreas, liver, peritoneum (distension, inflammation, irritation, toxins, foreign bodies).

  • Chemical Signals:

    • Endotoxins, waste products, certain hormones.

  • Vestibular Signals:

    • Motion sickness and vestibular disease.

  • Higher CNS:

    • Stimuli like pain, fear, stress, olfactory/gustatory cues.

Mechanism of Emesis

  1. Afferent signals ascend to the Vomiting Center in the medulla, primarily through the Chemoreceptor-Trigger Zone (CTZ).

  2. Vomiting Center initiates vomiting reflex through motor signals.

    • Phases include:

    • Prodromal Phase: Symptoms include drooling, lip licking, nausea.

    • Retching: Rhythmic contractions occur, followed by expulsion.

Drug Targets

  • Various receptors in the CTZ associated with vomiting include:

    • Dopamine (D2 receptors), Histamine (H1 receptors), Substance P (NK1 receptors), Acetylcholine (muscarinic), Serotonin (5-HT receptors).

Consequences of Vomiting

  • Potential effects may include dehydration, electrolyte imbalances (hypokalemia, hypochloremia), and esophagitis or aspiration pneumonia.

Regurgitation

Definition

  • Regurgitation is the passive expulsion of ingesta from the esophagus or forestomach without the symptoms associated with vomiting.

Mechanism

  • Controlled by local reflexes in the esophagus, where reverse peristalsis pushes food back into the mouth.

Causes

  • Conditions leading to regurgitation may include esophagitis, megaesophagus, and esophageal strictures.

Species Differences

  • Certain species such as horses and rodents have anatomical and physiological barriers that prevent vomiting, affecting feeding and digestion behavior.