BIOM2012 - MOD5 - Gastrointestinal System

What are the accessory organs of the digestive system?

• Teeth

• Tongue

• Salivary glands

• Liver

• Gallbladder

• Pancreas

What are sphincters, and which are important in the GIT?

Sphincters control the passage of food along the GIT.

• Upper oesophageal sphincter

• Lower oesophageal sphincter

• Pyloric sphincter

• Ileocecal sphincter

• Internal anal sphincter

• External anal sphincter

• Sphincter of oddi - allows bile and pancreatic juice to flow into small intestine

What is the anatomy of the GIT wall?

• Mucosa - inner epithelial layer with connective tissue, capillaries, neurons, immune cells, smooth muscle.

• Submucosa - loose connective tissue with larger blood vessels.

• Muscle layer - inner circular and outer longitudinal muscle with neurons in between.

• Serosa - outer connective tissue with squamous epithelial cells.

Inner most - mucosa, submucosa, muscle layer, serosa - outer most

What are the 6 steps of the GIT tract?

1. Ingestion

2. Secretion

3. Digestion (mechanical + chemical)

4. Absorption

5. Motility (mixing + propulsion)

6. Defecation

What are the digestive enzymes of the GIT?

Digestive enzymes breakdown macronutrients into smaller building blocks to facilitate their absorption by the GIT. 

1. Amylase - digests starch/glycogen into maltose then glucose. 

2. Proteases and peptidases - split proteins into small peptides and amino acids. 

3. Lipase - breaks TAGs into FAs and glycerol, and MAGs and DAGs. 

4. Nucleases - split DNA and RNA into nucleotides. 

What are the secretions from the stomach?

Hydrochloric acid:

• Decreases pH

• Kills bacteria and pathogens

• Denatures proteins 

Mucus - viscous secretion composed of water and HCO₃^- and mucin (glycoprotein)

• Protects stomach wall from aicd

GI hormones:

• Gastrin regulates digestive activity by:

  • Stimulating acid production

  • Promoting stomach muscle contractions.

Digestive enzymes:

• Pepsin - converts proteins → peptides

• Gastric lipase - removes 1 FA from TAGs

What are the 3 phases of gastric secretion and food processing?

1. Cephalic phase

• Triggered by sight,smell,taste,thought of food before it enters the stomach. 

• Brain stimulates vagus nerve to send signals to stomach to begin secretion of gastric juices. 

• Prepares the stomach for digestion. 

2. Gastric phase

• Triggered by presence of food in the stomach causing stretching/distension. 

• Distension activates stretch receptors.

• Partially digested proteins stimulate release of gastrin.

• Increased gastrin leads to gastric juice production, enhancing stomach contractions. 

• Responsible for majority of gastric secretion, ensuring proper breakdown of ingested food. 

3. Intestinal phase

• Triggered by entry of partially digested chyme from stomach into small intestine. 

• Secretion of hormones allowing for further gastric secretion and slowing gastric emptying:

  • Secretin - stimulates HCO3- and flow of bile 

  • CCK - triggers contraction of gallbladder and pancreas to release bile and enzymes to aid digestion

  • GIP and GLP-1 - stimulate insulin secretion.

Exocrine and endocrine tissues of the pancreas

Endocrine - Islets of langerhans (a- and B-cells)

• Secretes - insulin (B) and glucagon (a)

• Function - regulates BGLs

Exocrine - acinar and ductal cells

• Acinar - secrete digestive enzymes

• Ductal - secretes HCO3^--rich fluid to neutralise stomach acid. Also, transports enzymes.

Gallbladder and bile

Bile is made in the liver but is stored in and released by the gallbladder.

Gallbladder concentrates bile by absorbing water and electrolytes.

Bile release is stimulated by CCK which causes the gallbladder to contract, releasing bile into the cystic duct. Bile then flows into the common bile duct into the duodenum. 

What are the functions of the small intestine?

• Chemical digestion

• Nutrient absorption

• Mixing chyme with digestive juices

• Transport of undigested remains to large intestine

What are the secretions of the small intestine?

• Digestive enzymes (from enterocytes)

  • Maltase, sucrase, lactase

• GI hormones (endocrine cells)

  • Secretin, CCK, GIP, GLP-1

• Mucus (goblet cells)

• Bicarbonate (from pancreas)

Functions of GLP-1

• Increases insulin secretion

• Reduces glucagon secretion

• Reduces gastric emptying

• Reduces acid secretion

• Reduces appetite

• Increases satiety

Functions of the large intestine?

• Digestion of remaining food residues by enteric bacteria. 

• Absorption of remaining water, electrolytes, and vitamins. 

• Propulsion of faeces towards rectum by mass movements. 

• Defecation

• Secretion of mucus - helps moves faeces along intestine

• Storage and concentration of residues until defecation. 

What is the gut microbiota?

Community of microorganisms on multicellular organisms. 

Factors that affect gut microbiota composition

• Diet

• Antibiotics

• Lifestyle

• Cohabitation

• Environment

• Dysbiosis (imbalance of microbiota composition)

Key functions of gut microbiota

• Digestion

• Vitamin synthesis

• Immune system support

• Protection

• Production of signalling molecules

What are the 2 types of movement in the GIT?

1. Peristalsis - alternating waves of contraction and relaxation that propels GI contents along the digestive tract. Occurs in the oesophagus, stomach, SI, and LI. 

2. Segmentation - localised contractions that mix chyme with digestive juices, but do not propel it forward. Occurs in the SI and LI (slower).

What functions of the stomach are facilitated by peristalsis?

1. Gastric emptying

2. Gastric mixing

What is the process of gastric emptying?

1. Peristaltic contractions occur, sweeping food down towards the pyloric sphincter.

2. Contraction becomes more vigorous.

3. Strong peristaltic contractions propel chyme forward, also grinding it.

4. A small portion of chyme is pushed through the partially open pyloric sphincter into the duodenum.

   1. The stronger the contraction, the more chyme is emptied with each contractile wave.

What is the process of gastric mixing?

1. When peristaltic contraction reaches pyloric sphincter, it is tightly closed and no further emptying takes place. 

2. When chyme is propelled forwards and hits the sphincter, it is tossed back - mixing is accomplished bc chyme is being propelled forward and tossed backwards with each peristaltic contraction. 

How does defecation occur?

1. When faeces enters the sigmoidal colon and rectum, it stretches the walls, triggering the defecation reflex. 

2. Stretching activates sensory nerve fibres, sending signals to the CNS.

3. CNS activates parasympathetic motor fibres, travelling back to the colon and rectum. Parasympathetic efferent fibres innervate smooth muscles of the sigmoidal colon and rectum. 

4. Parasympathetic motor signals cause muscles of sigmoidal colon and rectum to contract, pushing faeces towards the anus. 

5. Internal anal sphincter relaxes in response to parasympathetic stimulation, allowing faeces to move into anal canal. 

6. External anal sphincter remains closed to back faeces until appropriate time for defecation.

7. External anal sphincter relaxes to allow faeces to be propelled out.

What is the enteric nervous system?

The nervous system of the gastrointestinal tract. 

Made up of enteric neurons that communicate extensively with each other. 

Provides major nerve supply to GIT walls to control motility. 

Contains 2 sets of intercommunicating nerve plexuses:

1. Submucosal (Meissner) plexus

2. Myenteric (Auerbach) plexus

What is the submucosal (Meissner) plexus?

Controls:

• Local secretions

• Blood flow

• Contraction of smooth muscle in mucosal layer

What is the myenteric (Auerbach) plexus?

Controls:

• Coordinating motility of GIT

• Peristaltic movements of GIT

What are the intrinsic and extrinsic neurons of the ENS?

Intrinsic neurons - lie completely within the wall of the GIT. 

• Make up short reflexes

Extrinsic neurons - autonomic neurons that bring signals from CNS to GIT. 

• Make up long reflexes

What are short and long reflexes of the ENS?

Short reflexes - enteric nerve plexuses in the gut wall act as a ‘little brain’, allowing local reflexes to begin, be integrated, and end within the GIT. 

• Made up of intrinsic neurons. 

Long reflexes - digestive reflexes that are integrated in the CNS. They respond to stimuli arising inside or outside GIT. 

• Made up of extrinsic neurons

  • Sympathetic stimulation inhibits digestive processes. 

  • Parasympathetic stimulation enhances digestive processes

How do short reflexes in the ENS work?

1. Stimulus - stretch in the stomach

2. Stretch receptors within stomach wall sense the stretch. 

3. Local enteric nerve plexus integrates signal and sends it to the effector glands to release gastrin. 

How do long reflexes in ENS work?

1. Stimulus - stretch in the rectum

2. Stretch receptors within stomach wall sense the stretch. 

3. Signal is sent to spinal cord (CNS). 

4. Signal is integrated at the nerve plexus. 

5. Causes contraction of smooth muscles of the rectum. 

Effect of autonomic and enteric control on the gut

Autonomic:

• Parasympathetic nerve action increases contractility, motility, and gut secretions.

  • Relaxes smooth muscle sphincters

• Sympathetic nerve action decreases contractility, motility, and gut secretions. 

  • Constricts smooth muscle sphincters

Enteric:

• Activation of myenteric neurons increase contractility and motility. 

  • Controls sphincter constriction

• Activation of submucosal neurons increase gut secretions.

What are the key functions of the liver?

• Blood glucose regulation

• Vitamin storage

• Bile production

• Nitrogen excretion

• Fat metabolism

• Detoxification

• Protein synthesis

• Waste management

Liver blood supply

25% arterial blood - delivered from hepatic artery. 

75% venous blood - delivered from hepatic portal vein

• Carrying blood from digestive tract

Blood leaves the liver via the hepatic vein (this is different from the hepatic portal vein). 

What are the 4 types of cells found in the liver?

1. Hepatocytes - main functional cells of the liver, responsible for metabolism, detoxification, protein synthesis, bile production. 

2. Liver endothelial cells - line the blood vessels of the liver. They facilitate the exchange of substances between blood and hepatocytes. 

3. Stellate cells - store vitamins and play a key role in liver fibrosis when activated. 

4. Kupffer cells - specialised macrophages that reside in the liver. They are responsible for phagocytosing pathogens, very mature erythrocytes, dead cells, and debris. 

What are lipoproteins? Describe what they do. 

Lipoproteins are complexes of lipids and fats that are responsible for the transport of hydrophobic lipids in blood. 

1. Large fat droplets enter the stomach. 

   1. They are not easy to digest due to small surface area. 

2. Fat droplets must be emulsified (broken down) by bile salts into smaller micelles. 

3. Micelles can better be attacked by lipases, thus we have TAG breakdown into FAs and glycerol. 

4. Cholesterol is actively transported into cells of the duodenum. 

5. When we package cholesterol, TAGs, and apolipoproteins together we get chylomicrons.

6. Chylomicrons are secreted by intestinal cells and enter the lymphatic system.

How are lipids transported in the body?

1. The liver releases VLDL molecules into the circulation.

   1. VLDLs deliver TAGs to other tissues.

2. As VLDLs offload TAGS, they become smaller and are classified as IDLs.

   1. This continues on until they become LDLs.

3. LDL deliver cholesterol to peripheral tissues.

4. In healthy individuals, LDLs bring back remaining cholesterol to the liver.

5. LDL receptors internalise LDL, bringing them into the liver for further processing.

6. Cholesterol is degraded and converted into bile acids (if we have too much) and is excreted as bile in the gut.

How is iron metabolised by the body?

1. Fe2+ leaves the duodenal enterocytes or macrophages via ferroportin. 

2. Fe3+, in the blood, binds to transferrin. 

3. Transferrin-bound iron can be taken up by cells via transferrin receptor 1. 

4. In the liver, iron is stored in ferritin. 

What are the phases of detoxification in the liver?

1. Phase I - Modification

• Chemical modification of compounds.

• Cytochrome P450 enzyme exposes/adds reactive groups, making the molecule more hydrophilic and reactive. 

2. Phase II - Conjugation

• Functional groups (introduced in phase I) are conjugated with polar molecules (glutathione, sulphate, glucoronate), making them more hydrophilic, facilitating excretion. 

3. Phase III - Secretion/Excretion

• Hepatocytes excrete products from phases I and II into bile or blood. 

• Some metabolites may require further metabolism if they are not hydrophilic enough. 

• Metabolites are. actively transported out of hepatocytes using membrane transport proteins and into the blood. The kidney can then excrete it via urine. 

How does the circadian clock work?

The circadian clock resides in the suprachiasmatic nuclei of the hypothalamus. 

The circadian clock synchronises peripheral tissue clocks in most cells and drives rhythmic physiology. 

Molecular circadian clock regulates circadian behaviour. 

All known circadian oscillators consist of negative feedback loops of gene expression. 

How does the circadian clock affect the GIT?

Liver - blood flow is reduced during the day and is higher at night. 

Bile - secretion into gallbladder (from liver) and duodenum is high during the day and low at night. 

Basal gastric acid - secretion spikes when we wake up and gradually increases throughout the day, is highest after we’ve gone to sleep, and decreases during the night. 

Small intestine - motility increases during the early morning, peaks midmorning, then decreases.