102 The Gastrointestinal System

Continuous with external environment

Approx 9m long: mouth ==> anus

GI system is designed to maximise absorption.

Overall function:

• Process ingested foods into molecular forms that are transferred to the body's internal environment

GI Tract:

Mouth, pharynx, oesophagus, stomach, small intestine & large intestine

GI System:

GI tract + accessory organs

• Salivary glands
• Liver
• Gall bladder
• Pancreas

Control mechanisms of the GI system regulate conditions in the lumen of the tract - not in the internal environment.

Governed by the volume and composition of the luminal contents - not by the nutritional state of the body, with few exceptions such as iron and other trace metals.

The GI tract has its own local nervous system: Enteric Nervous System

• Able to function independently of CNS.
• Composed of TWO nerve networks:

Submucosal Plexus

• Controls glandular secretion of mucosa
• Contractions of muscularis mucosae - thin layer of muscle which lines most of the GI tract

Myenteric Plexus

• Controls smoth muscle activity
• e.g. Peristalsis
  • Contractions of muscularis externa - composed of circular and longitudinal muscle layers

Distension of wall by luminal contents

- Mechanoreceptors

Chyme osmolarity (total solute concentration)

- Osmoreceptors

Chyme acidity

- Chemoreceptors

Chyme concentrations of specific digestion products

- Monosaccharides, fatty acids, peptides, amino acids

• These 4 stimuli act on muscle layers in wall of the GI tract & exocrine glands which secrete substnaces into the lumen. e.g. high lipid conc. leads to increased release of bile salts and lipase from pancreas

Hormones are secreted by endocrine cells which are scattered throughout the epithelium of the stomach & small intestines.

Various substances in chyme stimulate their release (amino acids / peptides / carbohydrates / lipids)

Most GI hormones reach their target cells via circulation:

• Released from opposite side of cell into blood.
• Not released directly into the lumen

• Hormone: Gastrin
• Site of Production: Antrum of stomach (stomach cavity) (epithelial endocrine cells)
• Stimuli for Release: Amino acids & peptides in stomach, inhibited by acid in stomach (somatostatin)
• Target Organ Responses (site of action): Stomach: Parietal Cells - stimulates HCl secretion, motility. Small intestine: stimulates ileum motility. Large intestine: stimulates mass movement.

• Hormone: CCK (cholesystokinin)
• Site of Production: Small intestine (intestinal endocrine cells)
• Stimuli for Release: Amino acids, peptides & fatty acids in small intestine
• Target Organ Responses (site of action): Stomach: inhibits acid secretion, motility. Pancrease & Liver: stimulates enzyme secretion - acinar cells, potentiates secretin's actions. Gall bladder: stimulates contraction and relaxes sphincter of Oddi - release of bile

• Hormone: Secretin
• Site of Production: Small intestine (intestinal endocrine cells)
• Stimuli for Release: Acid in small intestine
• Target Organ Responses (site of action): Stomach: inhibits acid secretioin, motility. Pancreas & Liver: stimulates bicarbonate secretion (NaHCO3); potentiates CCK's actions.

• Hormone: GIP
• Site of Production: Small intestine (intestinal endocrine cells)
• Stimuli for Release: Glucose & fat in small intestine
• Target Organ Responses (site of action): B-cells of Pancreas: stimulates insulin secretion. Also slows stomach churning rate

• Cephalic phase
  • Stimulated by sight, smell, taste, chewing.

• Gastric phase (gastrin release)
  • Initiation by 4 types of stimuli (contents of stomach):
    • Distension
    • Acidity
    • Amino Acids
    • Peptides

• Intestinal phase (GI hormones: Secretin, CCK, GIP)
  • Initiated by stimuli in intestinal tract:
    • Distension
    • Acidity
    • Osmolarity
    • Various digestive products

Chyme entering duodenum inhibits stomach activity

Peristalsis:

• Progressive, recurring waves of smooth muscle contractions
• Muscularis externa - composed of circular and longitudinal muscle layers
• Compresses and squeezes the GI tract.

Spincters:

• Act as valves that regulate passage or flow of material through the GI tract
• Respond to stimuli from nerves, hormones, and hormone-like substance and increase in pressure

• Where digestion begins
• Mechanical breakdown of food - mastication

Motility

• Chewed & mixed with saliva
• Facilitates swallowing

Secretion

• Saliva from salivary glands

Digestion

• Salivary amylase begins digestion of carbohydrates

Absorption

• No absorption of food, some drugs may be absorbed.

• Secreted by 3 pairs of salivary glands in the head
  • Drains into head via a series of short ducts
  • Secrete approx 1-1.5 litres of saliva per day

• Contains:
  • Mucus
  • Salivary amylase
  • Lysozyme

• 4 major roles:
  • Moisten & lubricate food (bolus)
  • Digestion of polysaccharides
  • Dissolve food
  • Antibacterial actions

Bolus of food is pushed by the tongue against the hard palate (roof of mouth) and then moves towards the pharynx

As bolus moves into pharynx, the epiglottis closes over larynx

Esophogeal muscle contractions push bolus towards the stomach. The epiglottis returns to its normal position.

Motility

• Transports food to stomach
• Constrictor muscles in the pharynx move the bolus into the oesophagus
• Peristalsis in oesophagus pushes the bolus toward the lower oesophagal sphincter at stomach

Secretion

• Mucus - lubrication

Digestion & Absorption

• No nutrient digestio or absorption

• increase parasympathetic activity = increase gastric motility
• increase sympathetic activity = decrease gastric motility

• Motility
• Peristalsis: 4 aspects
  • Gastric filling
  • Storing
  • Mixing
  • Emptying
• Secretion
  • HCl Mucus
  • Pepsin Intrinsic Factor
• Digestion
  • Reduces food to chyme. Carbohydrate digestion continues in the body of the stomach. Protein digestion begins in antrum of the stomach.
• Absorption
  • No food stuffs absorbed. Few lipid-soluble substances such as alcohol & aspirin

• The body secretes approx 2 litres per day - approx 0.16M concentration in stomach HCl
• It does not break down the lining of the stomach as the stomach lining is covered in a layer of mucus, there is a rapid cellular turnover and tight junctions.
• HCl activates enzymes
  • e.g. Pepsinogen ==> Pepsin
• Breaks up connective tissues & plant cells
• Denatures proteins
• Converts ingested ferric ions (Fe+3) to ferrous ions (Fe+2) which can be absorbed & used for haemoglobin synthesis
• Destroys ingested bacteria & pathogens

• Stimuli: Cephalic Phase - sight, smell, taste
• Pathways: Parasympathetic nerves to ENS
• Results: increased HCl secretion

• Stimuli: Gastric Phase - Distension, increased peptides, decreased [HCl]
• Pathways: Long & short neural reflexes & direct stimulation of gastric secretion
• Results: increased HCl secretion

• Stimuli: Intestinal Phase - Distension, increased [HCl], increased osmolarity, increased [nutrient]
• Pathways: Long & short neural reflexes; secretin, CCK
• Results: decreased HCl secretion

• Secreted by Chief cells in inactive precursor pepsinogen.
• Synthesised in active form as this prevents damage to cells, e.g. zymogen or proenzyme

• Exposure to low pH converted to pepsin
  • almost instantaneous at pH < 2
  • Pepsin also acts on pepsinogen
• Stimulation for its secretion is the same as for HCl

Carbohydrate: low to moderate level of glucose + sodium - increases fluid absorption

Sodium: low to moderate level increases fluid absorption

Osmolality: hypotonic to isotonic fluids containing NaCl and glucose - increases fluid absorption

Volume: increased volume increases emptying rate

Caloric content: increased energy content decreases emptying rate

Osmality: increased solute concentration decreases emptying rate

Exercise: intensity exceeding rate of 75% of maximum decreases emptying rate

pH: marked deviations from 7.0 decreases emptying rate

Hydration level: dehydration decreases gastric emptying and increases risk of gastrointestinal distress

The pancrease performs both exocrine and endocrine secretary functions but only exocrine is directly involved in GI function.

Exocrine: produces pancreatic juice

• Bicarbonate (HCO3-) 
• Pancreatic enzymes
  • amylase, trypsin, lipase, nuclease

Pancreatic Acinar Cells

• Zymogens = inactive form (proenzymes)
  • trypsinogen - cleaved by enteropeptidase (secreted by small intestine)
  • chymotrypsinogen - cleaved by trypsin (secreated by pancrease
  • procarboxypeptidase - cleaved by enteropeptidase

All are involved in the breakdown of complex peptides into amino acids

• Contains bile salts and bicarbonate
• Bile salts - emulsify fats
• Most reabsorbed in ileum and returned to the liver via the portal vein.
• Release stimulated by secretin in response to acid in duodenum
  • Bicarbonate serves to neutralise stomach acid
• Bile secretion is controlled by blood bile salt concentration. 

Most absorption and final stages of digestion occur in the small intestine

It is approximately 6m long.

Divided into 3 segments

• Duodenum
• Jejunum
• Ileum

Normally most of chyme is digested and absorbed in the first quarter of the small intestines - duodenum and jejunum.

Duodenum (25cm long) and Jejunum (2.5m long)

• Duodenum - receives digestive secretions from the gall bladder and pancreas through the 'hepatopancreatic ampulla' - where pancreatic and bile ducts merge.
• Absorb amino acids (active transport) 
• Monosaccharides (active transport) 
• Fatty acids (simple diffusion and endocytosis)
• + calcium, iron

Ileum (approx 3.5m long)

• Absorbs bile salts
• Vitamin B12
• Water
• Electrolytes

It takes approx 5 hours for materials to pass from the duodenum to the end of the ileum.

Villi & Microvilli

• Fingerlike projections extending into lumen of small intestine
• Increase surface area x600

Brush border

• Collective name for microvilli
• Enzymes - maltase, sucrase, lactase, aminopeptidase

Lacteal

• Single blind ended lymphatic vessel at centre of each intestinal villus
• Invoved in fat absorption

Motility:

• Segmentation - thoroughly mixes food with pancreatic, biliary & small intestine secretions

Sectretion:

• Juice secreted does not contain digestive enzymes
• Small intestine enzyme work intracellularly within brush border

Digestion:

• Pancreatic enzymes continue carbohydrate & protein digestion
• Brush border enzymes complete it
• Fat digestion accomplished
• Pancreatic lipase

Absorption:

• Surface area vast to aid absorption - brush border 

Segmentation - rhythmical contraction & relaxation

• Produces continuous division & subdivision of intestinal contents
• Major role = MIXING

Rhythm varies along length of intestine

• Duodenum - 12 contractions/min
• Ileum - 9 contractions/min

Segmentation intensity is altered by hormones (motilin), ENS and ANS

Dietary Carbohydrates (starch, glycogen, sucrose, lactose)  

Mouth - salivary amylase

Polysaccharides (sucrose, lactose, maltose)

Stomach - salivary amylase for a short while

Small intestine - pancreatic amylase, maltase, sucrase, lactase

Monosaccharides

Absorption through small intestine lining

Monosaccharides in the bloodstream.

Dietary Protein

Stomach - Pepsin, HCl

Polypeptides

Small intestine - trypsin, chmotrypsin, peptidases

Amino acids, dipeptides, tripeptides

Into the bloodstream

Carboxypeptidase of the brush border continues to remove amino acids from the carboxyl (-COOH) end.

Aminopeptidase of the brush border removes one amino acid at a time from the amino (NH2) end.

Dipeptidase splits dipeptides into separate amino acids.

Dietary Fat (primarily triglycerides)

Mouth - Lingual & gastric lipase

Tri-, di-, monoglycerides, fatty acids & glycerol in 'micelles'

Small intestine - Bile salts & pancreatic lipase

Short & medium chain fatty acids, glycerol ===> blood.

OR

Long chain fatty acids, monoglycerides, phospholipids, cholesterol ==> Micelles ==> Chylomicrons (intestinal cell membrane) ==> Lymph

Very little digestion takes place

Bacterial flora populate large intestine

• Ferment cellulose & other undigested carbohydrates

Food remains in colon ~24-72 hours

Segmentation - 1 contraction/30 mins

Mass movement

• 3-4 times per day (usually following a meal) wave intense contraction
• Spreads over transcerse segment toward rectum
• Increased by parasympathetic innervation

The longer faecal meterial stays in large intestine, the more H2O is reabsorbed

Anus normally closed by:

• Internal anal sphincter (smooth muscle, involuntary control)
• External anal sphincter (skeletal muscle, voluntary control) 

Defecation reflect

• Initiated by sudden distension of walls of rectum due to movement of faecal material into it

Fortunately the brain centres can override reflex signals - thus delaying defecation