W6 L5: Movement & coordination of the GI tract

Regulatory Mechanisms in the Gastrointestinal Tract

There are three principal control mechanisms involved in the regulation of GI function: 
1.Endocrine
2.Paracrine
3. Neurocrine

Movement and coordination of the GI tract

• The nervous system and endocrine system collaborate in the digestive system to control gastric secretions

• The digestion process can be divided into three phases- the cephalic phase, the gastric phase, and the intestinal phase. 

• These processes involves neuronal and hormonal activation

• Neuronal: Enteric and Autonomic, rapid response

• Hormonal: slow long lasting long range (endocrine) or short range (paracrine).

 

1. Cephalic phase

• The cephalic phase of digestion is the stage in which the stomach responds to sight, smell, taste, or thought of food. Readiness for the meal

• About 20% of total acid secretion occurs (before food even enters the stomach)

• Neural activation through nerve fibers from the medulla stimulate the parasympathetic nervous system of the stomach

• This stimulates acid and gastric secretion in the stomach (via parietal and G cells) – a conditioned reflex

Gastric glands and secretary cells of the stomach

1. Pariteal cells - produce both hydrochloric acid (produce acidic environment) and intrinsic factor (helps absorption)

2. Chief cell - secrete pepsinogen- the inactive proenzyme form of pepsin, breaks down proteins

3. Enteroendoendocrine (EEC) cell - secrete various hormones including gastrin and ghrelin

4. Mucous cell - secrete mucin which has several protective functions

2. Gastric phase

• 50-60% of total gastric acid secretion

• Swallowed food and semi-digested proteins activate gastric activity

• Neural & hormonal activation

• Stimulates gastric activity in two ways: by stretching the stomach and by gastric contents stimulating mechanoreceptors in the stomach

1. Stretch activates a parasympathetic reflex to the medulla oblongata

2. Medulla oblongata stimulates via vagus nerves secretions by:
 G-cells > gastrin (endocrine)
 ECL-endocrine cells histamine (paracrine)

3. Stretch of the stomach activates local reflexes, increasing stomach secretions

4. Gastrin & histamine enter circulation & stimulate more secretion

3. Intestinal phase

• 5-10% of gastric secretion

• The duodenum responds to arriving chyme and moderates gastric activity through hormones and nervous reflexes.

• Neural & hormonal activation

• Low pH inhibits parasympathetic nerves decreasing gastric secretions leading to ‘pyloric brake'.

• Local reflexes also inhibited by low pH inhibit gastric secretions

• Secretin and cholecystokinin (CCK) produced by duodenum both decrease gastric secretion

• Both promote the production of pancreatic juice and bile

• CCK slows gastric emptying emptying by contracting the pyloric sphincter 

Where is the pancreas?

• Lies behind and lower to the stomach on the left side of the abdominal cavity.

• Head: The widest and most medial part, connected to the duodenum.

• Tail: A narrow, tapered extension on the left side near the spleen.

• it's about the size of your hand  (about 15cm long)

 

The pancreas in digestion

• The pancreas influences digestion, glucose metabolism, and enzyme production.

Does this by two main functions:

1. Endocrine function  – secretes hormones directly into blood – help control blood sugar levels

2. Exocrine function – secretes digestive juices/enzymes into a duct – digest food directly

Endocrine function of the pancreas

• Islets of Langerhans  responsible for secreting two major hormones: insulin and glucagon

• Insulin (Beta Cells, ~75%):
  Lowers blood sugar by promoting glucose uptake and storage.

• Glucagon (Alpha Cells, ~20%): Raises blood sugar by stimulating glycogen breakdown.

• Somatostatin (Delta Cells): Inhibits both insulin and glucagon secretion.

Hormones secreted by the pancreas – Insulin & Glucagon

• Blood glucose is detected by β-cells

Insulin – key points

• Blood glucose is detected by β-cells

• Insulin is secreted from β-cells of the islets of Langerhans in response to an increase in glucose.

• Glucose uptake via Glut transporters lowering glucose uptake

• Glucose uptake via Glut transporters lowering glucose uptake

• Leads to anabolic reactions with target cells :
   the liver, the skeletal muscle and the adipose tissue

• Promotes the synthesis of protein and glycogen

Glucagon – key points

• Low glucose is detected by alpha islets cells

• Glucagon is released when blood sugar is low (including fasting, exercise, hypoglycemia)

• Similar to insulin, acts differently on different targets (brain, pancreas, liver, fat, heart)

• Glucagon leads to breakdown of substrates (catabolism)

•  Produces energy – glycogen -> glucose – glycogenolysis
  AA -> glucose - gluconeogensesis

Exocrine functions of the pancreas

• The exocrine pancreas plays a vital role in digestion.

• Acini cells produce and release digestive enzymes/juices into ducts leading to the small intestine – the duodenum.

 

Key enzymes and their roles

• Amylase – Breaks down carbohydrates > sugars

• Proteases (Trypsin & Chymotrypsin) – Break down proteins & protects against pathogens.

• Lipase – Works with bile from the liver to break down fats, enabling absorption of fat-soluble vitamins.

• Bicarbonate secretion to neutralise stomach acid (chyme). Protects the intestines from damage due to stomach acid

• Water & Salts: Help dissolve and transport enzymes.

Regulation of exocrine pancreatic function

1. Parasympathetic Nervous System stimulates enzyme release during digestion (insulin and pancreatic juice) - this aligns with the cephalic and gastric phases of digestion

2. Hormonal Regulation via:

Secretin – Stimulates bicarbonate-rich juice to neutralise stomach acid.
Cholecystokinin (CCK) – Stimulates enzyme-rich juice for fat & protein digestion.

This hormonal response aligns with intestinal phase:

• Secretin and CCK release in response to chyme entering the duodenum, released from Enteroendocrine cells (EECs)

Liver location and histology

• The liver is the body's second largest organ

• Weighing around 3 pounds. It is a roughly triangular organ that extends across the entire abdominal cavity, located just lower to the diaphragm

Liver location and histology

• The liver is the body's second largest organ

• Weighing around 3 pounds. It is a roughly triangular organ that extends across the entire abdominal cavity, located just lower to the diaphragm

The liver in digestion

• The liver is closely linked to digestion and is the first processing site for absorbed nutrients.

• 80% of liver is made from hepatocytes, arranged into functional units called lobules

Central role in digestion - Metabolism

• Stores and releases glucose for blood sugar balance.

• Metabolises fatty acids for energy and produces lipids.

• Processes amino acids, converting ammonia to urea for excretion.

Central role in digestion - Digestion

• Produces bile to emulsify fats for digestion. Bile secreted from gall bladder. Into duodenum

• Metabolises haemoglobin into bilirubin for bile formation.

Central role in digestion - Detoxification

• Neutralises toxins, alcohol, and drugs.

• Regulates hormonal balance by removing excess hormones.

Central role in digestion - Storage

• Stores vitamins A, D, E, K, B12, iron, and copper.

• Retains fatty acids from triglycerides.

Central role in digestion - Production

• Synthesises blood proteins (prothrombin, fibrinogen, albumins).

• Supports coagulation and maintains blood balance.

Two types of diabetes

Type 1 – from birth – lack of insulin

Type II – mature onset  - insulin resistance

Diabetes and insulin

• Insulin is the key to cells

• The receptor is the lock

• Type I diabetes – there is no key (insulin)

• Type II diabetes – the lock changes shape, insulin/key cannot open it

• NET RESULT OF BOTH IS NO GLUCOSE ENTERS THE CELLS > high blood sugar levels

What happens in diabetes

The Interplay Between Diabetes and Liver Function

• The liver is a primary target of insulin. Insulin Resistance:

• In type 2 diabetes, hepatocytes become resistant to insulin, leading to high blood sugar.

• Increased Glucose Production:

• The liver overproduces glucose, contributing to hyperglycaemia

• Non-Alcoholic Fatty Liver Disease (NAFLD): Insulin resistance promotes fat buildup in the liver.

• NAFLD can progress to more severe conditions like non-alcoholic steatohepatitis (NASH), cirrhosis, and liver failure