Gastroenterology

Regulation of Substrate Metabolism

• Stage 1: Digestion occurs in the gastrointestinal tract lumen.
• Stage 2: Anabolism and formation of catabolic intermediates take place within tissue cells.
• Stage 3: Oxidative breakdown happens in the mitochondria of tissue cells.
• Proteins break down into amino acids, carbohydrates into glucose and other sugars, and fats into glycerol and fatty acids for energy.

Nerve Supply to the Gut

• The enteric system, located within the GI tract walls, is often referred to as the 'gut brain'.
• This system is responsible for controlling movement and secretion in the gut.

Brain-Gut Interaction

• Psychological or social stress can lead to digestive problems.
• Severe stress can trigger the fight-or-flight response, causing digestion to slow down or stop.
• Less severe stress may temporarily disrupt the digestive process, leading to abdominal pain and other gastrointestinal symptoms.
• Persistent gastrointestinal issues might heighten anxiety and stress levels.

Gut Microbiota

• The microbiota (gut microbial community) is considered a "super-organism".
• The microbiota plays a vital role in maintaining gut homeostasis.
• About 100 trillion bacteria are associated with the gastrointestinal tract.
• The gut microbial community coevolved in a symbiotic relationship with the human intestinal mucosa.
• The primary role is salvaging energy via fermentation and absorption of short-chain fatty acids (SCFA).
• Gut microbiota also participates in synthesizing vitamins B and K.
• Gut microbial symbiosis has a close relationship with diseases of different systems including obesity, IBD, atherosclerosis, diabetes, liver disease, metabolic syndrome, and emerging infectious diseases.

Gastrointestinal Tract

• The GI tract is the largest neuroendocrine organ.
• Enteric nervous and entero-endocrine systems are integrated within the GI tract, extending to specific brain areas.
• It produces a large number of peptidergic hormones and regulatory factors.
• These are primarily localized in the mucosa of the GI tract and pancreas.

Entry to the GI System

• The oral cavity is the entry point to the GI system.
• Teeth and tongue are for mechanical processing, moistening, and mixing food with salivary secretions.
• Saliva mixes with chewed food for swallowing.
• The salivary glands consist of 3 pairs: parotid, sublingual, and submandibular.

Saliva Contents

• Saliva is 99.5% water, helps to lubricate and dissolve food.
• Saliva contains mucus glycoproteins, electrolytes, and mucins which protect the oral mucosa and lubricate food.
• It has a-amylase which hydrolyzes complex carbohydrates.
• Lingual lipase hydrolyzes dietary triacylglycerides.
• Antibacterial and antiviral compounds (IgA) are present.

Taste Buds

• Trigger the creation of pressure to swallow by using the tongue.
• A complex reflex response in the swallowing centre in the brain regulated by swallowing.
• The trachea is closed off when swallowing and prevents food entering the trachea and going into the lungs.

Oesophagus

• Transports materials to the stomach.
• Smooth muscles stimulated by nerves cause food to move down the oesophagus by peristalsis.
• The lower oesophageal sphincter (LES) relaxes for bolus to pass into the stomach.
• The lower oesophageal sphincter prevents gastro-oesophageal reflux.

Heartburn

• Heartburn is a burning feeling in the chest, often due to regurgitation.
• Usually not a cause for concern, but contents of the stomach can leak out into the oesophagus.
• Frequent heartburn may indicate gastro-oesophageal reflux disease, or GERD.
• Antacids neutralize stomach acid, providing temporary relief.
• H2 blockers lower stomach acid production.
• They help prevent heartburn if taken about 30 mins before meals.
• Proton pump inhibitors block stomach acid production and are more effective than H2 blockers.

Barrett's Oesophagus

• A complication of chronic gastrointestinal reflux disease (GERD).
• Occurs only in a small percentage of individuals with GERD.
• Treatment involves acid-suppressing drugs.

Stomach Structure

• Functional divisions: Fundus (upper portion for grinding, mixing, and storing), Body (middle section for digestion with HCL and pepsin secretion), and Antrum (slow, methodical movement of chyme to the duodenum).

Gastric Electrical Activity

• Antral contractions under gastric nerve control occur regularly due to the stomach's pacemaker.
• Gastric emptying moves about 1-5ml of chyme twice per minute and is affected by GI hormones and neuropeptides.
• The composition of food can also affect this.
• A meal usually takes 2-6 hours to be process, protein and carbohydrates process faster than fat.
• A gastric electrical stimulator can be implanted to send mild electrical pulses to the nerves and smooth muscle of the lower stomach.
• This helps decrease nausea and vomiting for delayed gastric emptying.

Gastric Juices

• Originate from 3 types of gastric glands:
• Cardiac glands (junction of oesophagus and stomach)
• Oxyntic glands (body of the stomach)
• Pyloric glands (antrum)
• Cardiac glands are heavily branched, tubular glands mainly containing mucus-producing cells.
• These glands have shallow gastric pits and secrete mucus.
• Oxyntic glands produce most of the HCL (parietal cells) and enzymes (chief cells) secreted in stomach.
• Pyloric glands: branched, coiled, tubular glands with specialized enteroendocrine G cells which secrete gastrin in response to eating.
• Gastrin stimulates pepsin and acid secretion by oxyntic glands.
• Other endocrine cells secrete serotonin and somatostatin, controlling insulin, glucagon, gastrin, and growth hormone secretion.

Stomach Contents

• The stomach contains a high concentration of HCL, resulting in a low pH of ~2.
• HCL activates pepsinogen to pepsin in the stomach's lumen.
• Denaturation of proteins allows pepsin to have a proteolytic effect.
• HCL also aids in nutrient release from organic complexes and acts as a bactericidal agent.

Enzymes and Secretions

• Pepsin: is a proteolytic enzyme, secreted as pepsinogen from chief cells, converts to pepsin in an acidic environment.
• α-amylase: hydrolyses starch.
• Gastric lipase
• Mucus glycoproteins, water, bicarbonate: lubricate and protect gastric mucosa.
• Pepsin is responsible for initial digestion of proteins.

Regulation of Gastric Secretions

1. Taste or smell of food, tactile sensations, and even thoughts of food stimulate regions in the brain.
2. Parasympathetic action potentials transfer to the stomach using the vagus nerves which activates enteric neurons
3. Neurons stimulate the secretion by parietal and chief cells (HCL and Pepsin) and the secretion of hormone gastrin and histamine.
4. Gastrin is carried through circulation back to the stomach stimulating further HCL and pepsin secretion.

Peptic Ulcers

• Peptic ulcers an occur in the lining of the stomach (gastric) and in the lining of the duodenum, located just below the stomach (duodenal).
• Generally causes indigestion, occasionally bleeding.
• Weight loss and persistent vomiting are concerning symptoms.
• Pepsin can corrode the stomach and duodenum lining.
• The lining protects itself using mucus and fluids, an ulcer may occur if they can't overcome the ulcer.
• NSAIDS (e.g., nurofen, aspirin) interfere with the gastric and duodenal lining and increase the risk of peptic ulcers.
• Helicobacter pylori (H. pylori) infection can cause peptic ulcers.
• Tests for H. Pylori infection are blood tests, breath tests (labelled urea), or biopsy stool tests which are only valid when not taking any antibiotics.
• The treatment for H. pylori is a one-two week course of antibiotics plus a tablet to reduce stomach acid, taken twice a day.
• Clinical outcomes of H.pylori infection include
• Asymptomatic or chronic gastritis (>80%)
• Chronic atrophic gastritis Intestinal metaplasia (15-20%)
• Gastric or Duodenal ulcer (<1%)
• Gastric cancer MALT lymphoma (<1%)

Lower GI Tract

• Small intestine: duodenum, jejunum, ileum.
• It averages 5-6m in length.
• Around 90% of absorption occurs in the small intestine, and it is the major site of digestion
• Intestinal and hormone secretion, and protection against infection also occurs in the small intestine
• Chyme from the stomach is about pH 2 due to the gastric acid content and the duodenum is protected by the secretion of Brunner's glands and pancreatic secretions
• The stomach secretes into the lower duodenum

Brunner's Glands

• Located in the first few cm of the duodenum and produces viscous alkali secretions at pH 8-9.
• Brunner's glands neutralizes stomach acid and deactivates pepsin.
• The glycoproteins found here helps to protect the epithelial lining as well as anti-microbial peptides.

Gall Bladder

• Bile collects in the gallbladder for concentration and storage.
• Cholecystokinin (CCK) stimulates contraction.
• Bile helps as a detergent and works to decrease the surface tension of fat to create micelles.
• Lipase digests bile, and acids with phospholipids form small spherical complexes called micelles (<10nm).
• Enterohepatic circulation involves the liver synthesizing (0.4 g/d) and secreting (24 g/d) bile, Biliary Transport and Storage, going into the Duodenum, then Jejunum, then Ileum, and then Colon, after which Portal Venous Return (>95% of Biliary Secretion) occurs and then Fecal excretion (0.4g/d).
• Gallstones are caused by an imbalance in substances that make up bile, occasionally they can cause a blockage to bile flow.
• Symptoms such as stomach pain, sickness or yellowing can occur.
• Surgery is normally conducted to resolve.

Exocrine Pancreas

• Pancreatic secretions contain electrolytes, bicarbonate (neutralizes and maximizes enzyme activity).
• Enzymes digest 50% of carbohydrates, proteins, and about 90% of ingested fat.
• Islets of Langerhans are responsible for endocrine secretions.
• Beta cells, Alpha cells and Delta cells.

Digestion in the GI Tract

• Carbohydrates: Amylase digests in the mouth/stomach (salivary glands) producing Disaccharides which are small intestine brush border are digested to create Monosaccharides.
• Protein: Pepsin digests in the stomach (chief cells) to produce peptide fragments, followed by Trypsin attacks the protein in the small intestine (exocrine pancreas) to produce Amino acids and a few small peptides.
• Fat: Lipase digests triglycerides in the small intestine (brush border) into fatty acids and monoglycerides. Bile salts (liver) are used to emulsify large fat globules by pancreatic lipase.

Absorption in the Small Intestine

• Occurs through structure of villi.
• Absorption in villi has microvilli, muscle layers, hepatic portal vein, lacteal, lumen, capillary bed.
• Absorption occurs in the small intestine using absorptive and secreting cells.
  • 200,000 microvilli x mm² and a capacity greater than that consumed/day.

Small Intestine Structure

• Villi structure changes along the small intestine:
• Duodenum: Villi with a leaflike shape.
• Jejunum: Villi have a finger-like shape.
• Ileum: Villi are shorter.
• Intestinal crypt (of Lieberkühn) components:
• Villi, Lamina propria, Opening of a crypt, Intestinal crypts, Muscularis mucosa, Enterocytes, Goblet cell, Mitosis, Endocrine cell, Undifferentiated cells, Paneth cell.
• Intestinal Epithelial Cells are differentiated by Enterocyte, Secretory (Goblet, Paneth, and Enteroendocrine) and Stem cells.

Cells fo the Small Intestine

• Goblet cells: responsible for the production and maintenance of the protective mucus blanket.
• Enterocytes: The absorptive cells, taking up water, ions, and CHO, amino acids, lipids, vitamins and bile acids.
• Paneth cells: Involved with host defense against microbes
• Endocrine cells: Produce true hormones released into the blood including (incretins) and CCK

Digestion and Absorption

• Most nutrients are digested prior to absorption in both lumen and brush border.
• Absorption in enterocytes occurs via diffusion, active transport, and facilitated diffusion.
• Most nutrient absorption occurs in the upper small intestine.

Coeliac Disease

• This is a common inflammatory disease of the small intestine (prevalence 0.5-1%).
• Consuming gluten in foods (10–20 g per day) causes this disease.
• A genetically predisposed condition (HLA-DQ2/8)
• Signs of coeliac: dermatitis herpetiformis Duhring, auto immune diseases such as type 1 diabetes.
• Most cases are oligosymptomatic; food intolerances, intestinal infections, and irritable bowel syndrome, diarrhoea
• If more serious: Wt loss, vitamin and mineral deficiencies, Blood clotting, weakness in muscles, osteoporosis, nerve damage.
• Gluten peptides that are not degraded by gastrointestinal enzymes can be taken up across the small intestine and shown in some types of antigen-presenting cells. HLA-DQ2 or HLA-DQ8 (about 90 and 10%) of with coeliac disease.
• A definitive diagnosis will show- celliac associated antibodies (endomysium) and small-intestine mucosa, which can be avoided by a gluten-free diet.

Large Intestine

• Similar histological layers to the small intestine, without villi.
• More goblet cells than in the small intestine.
• Secretions mostly consist of mucus from goblet cells, which protects and acts as a lubricant.
• It functions to desiccate and compact and lubricate the faecal bolus.
• Bacteria also plays a role

Appendix

• Has unknown useful purpose.
• Suspected functions: Hosting good gut flora and cultivating them; potential role in immune function to expose leukocytes to antigens.

Appendicitis

• Typically starts as a pain in the middle of the abdomen, moving to the lower right.
• Is accompanied by feeling sick, vomiting, and/or loss of appetite.
• Treatment involves surgery, by key hole surgery which is conducted through three small cuts for minimal damage and fast recover process.
• Around 40,000 people are admitted to hospital with it each year in England.
• Bursted appendixes leads to bacteria and blood poisoning.

Ulcerative Colitis

• Ulcerative colitis is a chronic diseases of intestinal inflammation.
• Only involves inflammation of the colonic portion of the gastrointestinal tract rather than the intestine as a whole.
• Superficial inflammation of colon rather than entire intestinal wall.
• Inflammation in ulcerative colitis is continuous, while Crohn's disease may skip areas.
• Common symptoms is diarrhoea mixed with blood and having and increased risk of colon cancer.
• To prevent the flaring of inflammation, there should be continual treatment with medication.

Rectum

• Its function is to as temporary site for faeces.
• Expansion of the rectal stimulate stretch receptors.