Introduction to Human Physiology - 8 Gastrointestinal Tract

Source: My personal notes from Introduction to Human Physiology | Coursera

Gastrointestinal System - General Structure and Function

• GI Tract that enables us to bring nutrients, electrolytes, water in the body.

Gastrointestinal Tract and Glands

• It is a long tube. Food comes in through mouth.
• e.g. eat steak and potatoes (complex materials). convert them to amino acids, sugars
• Processes:
  • Fragmentation: small chunks of food to allow enzymes to act on them. Daily we take 2-3 L of fluid and food.
  • Digestion: Inside stomach, small intestine (as much as 9L of fluid is present after body adds around 7L of fluid for digestion) Molecular breakdown.
  • Absorption: material goes into the body
  • Anus: waste materials that cannot be used by body. Usually only 200-500 mL is left daily.
• Material moves due to smooth muscle contraction.
  • Salivary gland moistens food, allowing food to slide down esophagus
  • Liver and pancreas secrete chemicals to aid digestion.
• Sphincters control gating of material.
  • Voluntary Sphincters at top and bottom of tube
  • Involuntary Sphincters (esophagus > stomach, stomach > small intestine, inside intestine)

Anatomy of the Gastrointestinal Tract

Looking at the “tube”

• Muscularis externa = smooth muscle. When it relaxes, tube gets larger. Like a milking action.
• Lumen = inner most part of tube along with epithelium. Epithelium is like skin and can survive wear and tear from mouth to esophagus and near anus area.
• Stomach has secretory elements
• Small intestine absorbs

Stomach Cells and Function

• 3 types of cells

• Glands are in dipping part

• Surface and neck cells secrete mucus to protect from stomach acid.

• Parietal cells are in “dipping part”. They secret acid.

  • Intrinsic factor (carrier) for vitamin B12 absorption

• Chief cells

  • “-ogen” - inactive enzyme

  • Pepsinogen goes into lumen and is converted to pepsin in presence of HCl (hydrochloric acid)

Secretion of Gastric Acid (HCl)

• Done by parietal cells. Parietal cell shown below.

• Basal side faces blood capillary, apical side faces lumen.

• Carbonic anhydrase reaction to give bicarbonate and H+

  • H+ pumped into lumen, K+ is pumped out } via H-K ATPase (proton pump)

  • HCO3- goes back to blood via transporter

  • HCl is generated in lumen.

  • pH of lumen can be pH 2.0 - very strong acid

Intrinsic factor (IF), also known as gastric intrinsic factor (GIF), is a glycoprotein produced by the parietal cells of the stomach. It is necessary for the absorption of vitamin B12 (cobalamin) later on in the small intestine.

Acid Secretion in Fed and Faster States

• In fed state (food is present), lots of HCl is generated. After 90 minutes, acid secretion decreases.

• Food buffers free protons. As food leaves stomach and free protons increase, so after 200 mins, pH drops.

General Concepts

Regulation of Acid Secretion

• Acid secretion in fed and fasted states

• Gastric ulcers and treatment

Secretion of Gastric Acid (HCl)

• Blood separated by interstitial space.

• Cl- comes from blood and goes via transporter to lumen.

• K+ balances protons into lumen via transporter

Acid Secretion in Fed and Fasted States

• pH from 2 to 5 (food buffers pH, free H+ protons are bound by food)

• pH back to 2 as food leaves stomach

Regulation of Stomach Acid

Cephalic Phase

• Acid is caustic and only secreted for use.

• Cephalic phase / “Feed forward” phase causes pre-secretion <— see, smell food. Phase activates H-K ATPase pump.

  • Parasympathetic Nervous System (Vagus nerve) signals (acetyl choline)

  • Gastrin is secreted and received on parietal cells’ receptors.

  • ECL cell secretes histamine in response to gastrin.

  • 3 signals that drive proton pump:

    • Acetyl choline

    • Gastrin (hormone)

    • Histamine (paracrine)

  • Accounts for 40% of acids in feeding state

Positive Regulation in Gastric Phase

• Stomach walls stretch, increasing stomach volume

• Gastrin is secreted, proton pump activity increased.

• ECL secretes histamine.

• Accounts for 60% of acid in feeding

[H+] Mediates Negative Feedback

• Free protons provide negative feedback in antreum of stomach.

• D cell detects [H+] and can secrete somatostatin (an inhibitor paracrine) to inhibit gastrin.

• Secretin hormone from duodenum binds to G cell and inhibits gastrin.

Causes and Treatment of Ulcers

• Mucus barrier usually protects epithelial cells of the stomach. In between cells and mucus, there is pH = 7 (neutral) barrier.

• NSAIDs (non steroid anti inflammatory drugs) such as ibuprofen (aspirin) erodes the barrier by inhibit synthesis of barrier.

• Causes:

  • Excess HCl secretion

  • Pathology - cause of ulcers is actually heliobacterium pylori which live in between cells and mucus and erode the mucus barrier. About 50% of people are infected, though only 15% of people are susceptible to the bacteria.

Treatment

• Bicarbonate - “TUMS” - a base that titrates the acid in the stomach to raise pH

• Histamine receptor antagonist - “Tagamet” - reduce acid generation by reduce histamine receptor effectiveness

• Proton pump inhibitor - “Nexium”. Prevents proton pumps from synthesizing. Reduces acid greatly, but takes 24-48 hours. Pumps must be replenished on cell surfaces and inhibitor prevents their synthesis.

General Concepts

Digestion and Absorption

• Explain and id locations of digestion and absorption

• Absorption of water

• Diarrhea

Control of Digestion

• Acidic chyme (low pH), enters into the duodenum (first part of the small intestine). It enters in small amounts to allow complete digetion.

• Fat is the last thing to enter the duodenum since fat sits on top of water based solutions and acid.

• If hypertonic solution (higher solute concentration, low water concentration solution) enters into the duodenum, water rushes into the small intestine, causing stretch.

• Food materials are broken down in lumen of small intestine.

• Large intestine/colon allows water absorption.

• Intestine:

  • CHO = carbohydrates

  • GLP-1, CCK, Secretin are hormones

  • Enzymes (zymogens) are delivered to the duodenum by pancreas

  • Bile salts are stored in the gall bladder and CCK causes the bile to be delivered to the duodenum. They are a detergent like liquid.

  • Secretin regulates acid and also signals pancreas duct cells to secrete bicarbonate (HCO3-) to neutralize acidic chyme. It makes an alkaline environment to allow the pancreatic enzymes to degrade food.

Pancreas Exocrine cell

• Shaped like an eye dropper like a ball with duct cells coming off end

• Secrete into duodenum:

  • zymogens

  • bicarbonate

Absorption of Nutrients and Water

• Look at inside of small intestine and digestion and absorption.

• Lumen epithelial cells have folds (villi and microvilli). The folds increase surface area of absorption. Size is like a tennis doubles court.

• Sodium Glucose Transporter (SGLT). They transport glucose through cells to blood to another GLUT. Called Secondary Active Transport.

  • Gatorade = A story about oral rehydration. There was a Florida football team called the Gators and the coach was concerned about player dehydration on hot days. The coach visited a nephrologist (kidney specialist) about his concern and a drink was proposed consisting of salt, glucose, water, and other electrolytes. Gatorade uses the SGLT to rehydrate the body.

• a.a. = amino acids, like SGLT are transported to blood and delivered to liver. They are secondary active transport.

• Na/K ATPase is in all cells.

• Di/tri-peptide transporter (pepT) use a proton transporter, degraded into a. a. inside cell.

Water is also absorbed to maintain an isotonic solution for blood.

Fat Absorption

• Last to leave stomach as they float on top

• Fat drops and bile (detergent) enter intestine, fat droplets are separated by bile

  • Collipase binds to fats and lipase cleaves fats

  • Fats broken to monoglycerides, free fatty acids, cholesterol - can be moved through diffusion and transporters

• Amounts are combined into chylomicrons. They are large particles and cannot move into blood. Chylomicrons move into the lymphatic system and move to heart and then to blood.

Ileum (separate from duodenum)

Reabsorbs water. 2 L of food + 7 L from body —> 7 L reabsorbed

Large Intestine Concentrates Waste

• Usually only 200-500mL of feces is excreted / day

• As Na+ and Cl moves, water follows as well.

• Lactose intolerance - lactose sugar cannot be cleaved in small intestine due to a missing enzyme that normally breaks it down into small sugars.

  • Lactose moves into the colon as a large sugar and it also holds water. Causes watery feces. Very watery feces = diarrhea. Diarrhea also causes loss of bicarbonate.

Water Absorption in Faster State

How do you move water from an isotonic state lumen to isotonic state in blood?

• Between cells there is a tight seal on lumen side.

• Na/K ATPase can change concentrations between cells.

 

Disorders of the Gastrointestinal Tract

Electrolytes and Diarrhea

Types of diarrhea: secretory and osmotic

Secretory

• Imbalance of ions in system. Too many ions in large intestine/colon which holds water.

• Causes dehydration.

• Cholera: treatment is to remain hydrated and outlast the bug. The bug will eventually die in the GI tract. Rehydrate with salt, glucose, and water.

Osmotic

• e.g. lactose intolerance or solutes that cannot be absorbed by the small intestine.

• Unabsorbed solutes are osmotically active and will hold water through the GI tract until it is excreted.

Discriminating between the Two Types

If someone has diarrhea, how can you tell the difference?

Have the person stop intake of food and fluids they do not normally have. The secretory diarrhea will continue; however, the osmotic diarrhea should stop after a while since all solutes have been excreted.

General Concepts

• GI tract emptying takes around 4 hours

• Isotonic to body is 300 mOsm at all times.

Motility

• Movement of materials through GI tract

General Anatomy

2 layers of smooth muscle = muscularis externa

Activity of 2 layers is coordinated via the enteric nervous system between 2 layers. Independent of CNS.

Electrical Slow Waves = Pacemakers

• Within fundic region of stomach + small and large intestines there are pacemaker cells (unstable action potentials) for smooth muscle.

Intestine: Action potential > contraction

Stomach: electrical slow waves > contraction

• Regulation by PNS and SNS.

  • SNS hyperpolarizes cells, longer action potential times and delays contraction

  • PNS reduces cell potential allowing easier action potential / contraction.

Segmentation: Motility in the Fed State

Lumen segments move food bolus (bunches)

1. Contraction by inner muscle mass
2. Relaxed by inner muscle mass
3. Contraction …
4. Relaxed …

Enhances absorption, breaks down food.

• Segmentation contractions (or movements) are a type of gastric motility.
• Unlike peristalsis, which predominates in the esophagus, segmentation contractions occur in the large intestine and small intestine, while predominating in the latter.

Peristalsis: Motility in the Fed State

Segmental movement of food bolus from mouth to anus.

• Outer muscle layer contracts shortening tube, while inner muscle layer widens the tube.
• Set with pacemakers and enteric nervous system (ENS). The enteric nervous system (ENS) or intrinsic nervous system is one of the main divisions of the nervous system and consists of a mesh-like system of neurons that governs the function of the gastrointestinal system. It is now usually referred to as separate from the autonomic nervous system since it has its own independent reflex activity.

Migrating Motor Complex in Fasting

During fasting, movement is different.

MMC sweeps clean GI tract to remove bacteria and remaining food.

Sphincters

• Different sections are isolated by involuntary sphincters to protect areas from acid of stomach.

• Sphincter turns off tonic inhibition to allow acid chyme into to duodenum during digestion.

Mass Movements

Waves of contraction inside large intestine. They are not peristalsis waves as they involve only the inner layer of the muscularis externa.

Vomiting

• Dumping syndrome of the stomach
• Vomit may have greenish colour due to gall bladder bile delivered to duodenum
• Vomiting is not due to reverse of regular motility but rather a change in thoracic cavity pressure. Pressure controlled by medulla.

General Concepts

Tonic contractions are those contractions that are maintained from several minutes up to hours at a time. These occur in the sphincters of the tract, as well as in the anterior stomach. The other type of contractions, called phasic contractions, consist of brief periods of both relaxation and contraction, occurring in the posterior stomach and the small intestine, and are carried out by the muscularis externa.