Gastrointestinal tract Flashcards
Describe the main components of the GI tract
mouth, oesophagus, stomach, (pancreas, liver, gallbladder), small and large intestine, anus
Discuss the control mechanisms of the GI tract
- autonomic nervous system
- parasympathetic nerves stimulate digestion
- sympathetic nerves inhibit digestion - Enteric nervous system - 2 nerve plexus in the gut walls can sense the luminal contents and control muscles and glands (2nd brain)
- myenteric plexus and submucosal plexus
- has sensory, motor, interneurone, muscle and gland components - Gut peptides - paracrine and hormonal
(neural, paracrine and hormonal)
Describe gastric functions (stomach)
Motility - gastric accommodation, trituration, gastric emptying
Digestion - digestive juice
Protection - acid/proteases, mucus
Absorption
Discuss the morphology of the gastric glands
Gastric pits - indentations in the stomach epithelial lining which are the entrances to 3-5 tubular shaped gastric glands
then other types of cells in the gland - mucous neck, parietal, chief, enteroendrocine
How is the function of the GI tract achieved overall? (4 ways)
Digestion
chemical - enzymes
mechanical - motility (mixing, grinding)
absorption
Approx how much saliva in ml is secreted?
1500ml
Approx how much bile, pancreatic and intestinal secretions in ml?
bile - 500ml
pancreatic - 1500ml
intestinal - 1500ml
Approx how much is absorbed in ml from the small intestine?
8500ml
What are the transit times in the mouth, oesophagus, small intestine and large intestine?
Mouth - 1 min
Oesophagus - 10 seconds
small intestine - 3-6 hours
large intestine - 1-2 days
What are the 4 levels of structural organisation of the GI tract?
Mucosa
Submucosa
Muscularis
Serosa
What are the 4 levels of structural organisation of the GI tract?
Mucosa (mucous epithelium, lamina propria, muscularis mucosse)
Submucosa
Muscularis (circular and longitudinal muscle layers)
Serosa (connective tissue and peritoneum)
What is swallowing/deglutition?
process by which food passes from mouth to stomach
What are the 3 phases of swallowing?
Oral phase
Pharyngeal phase
Oesophageal phase
Which phases of swallowing are voluntary and involuntary?
Oral - voluntary
Pharyngeal - involuntary
Oesophageal - involuntary
What happens in the oral phase?
Tongue moves upwards- compress bolus against hard palate. Respiration inhibited
Retraction of tongue forces bolus into pharynx, closes of oral cavity
What happens in the pharyngeal phase?
Involuntary movement pushes bolus from pharynx into oesophagus
Soft palate reflected backward closing nasal pharynx
What happens in the pharyngeal phase?
Involuntary movement pushes bolus from pharynx into oesophagus
Soft palate reflected backward closing nasal pharynx
how long and wide is the oesophagus?
25cm length and 2cm in diameter from pharynx to the stomach
What happens in the oesophageal phase?
Upper oesophageal sphincter relaxes and bolus moves into oesophagus
Start primary peristaltic wave (Vagal – vagus nerve)
Secondary peristaltic wave (Enteric)
Lower oesophageal sphincter relaxes
What does the lower oesophageal sphincter prevent?
Prevents reflux of material back into the oesophagus
What are the 4 main regions of the stomach?
Cardia, Fundus, Body, Pylorus
What are the two openings of the stomach?
Oesophagus and duodenum
What are the 4 main regions of the stomach?
Cardia, Fundus, Body (Corpus), Antrum/Pylorus
What is the role of mucus in the stomach?
Mechanical abrasion
Prevents autodigestion
What is the function of gastric juice?
Initiates the digestive process (proteins)
What is the composition of Gastric juice?
Water and ions
HCL - low pH prevents bacterial growth and catalyses cleavage of pepsinogens to pepsin so active form is not denatured by HCL
pepsinogens - pepsin breaks down proteins into peptides
intrinsic factors - glycoproteins bind to b12 allowing digestion in ileum
mucus - protects gastric mucosa - antibacterial/antiyeast
gastrin - hormone from G cells that regulate acid secretion
What are the 3 gastric glands in the stomach and what do they secrete?
Cardiac glands - secrete mucus and HCL
Oxyntic glands - mucus, hcl, pepsinogen, intrinsic factor
pyloric glands - mucus, pepsinogen
What cells do you find inside a gastric pit?
Mucus neck cells - produce mucus
parietal cells - hcl and instrinsic factors
chief cells- pepsinogen
endocrine cells - g cells (gastrin producing to stimulate acid secretion) and d cells (somatostatin to inhibit acid secretion)
What cells do you find inside a gastric gland?
Mucus neck cells - produce mucus
parietal cells - hcl and instrinsic factors
chief cells- pepsinogen
endocrine cells - g cells (gastrin producing to stimulate acid secretion) and d cells (somatostatin to inhibit acid secretion)
What is the gastric pit?
Opening/entrance/indentations that leads to the gastric gland
What is the gastric secretory response to a meal?
Cephalic phase 30% - sight, smell, thought of food triggers gastric secretion instigated by vagal fibres
Gastric phase 60% - food entering stomach stretches it which triggers secretion via long vagal and short myenteric reflexes
Intestinal phase 10% - intestinal gatrin release in response to distension of duodenum and/or products of protein digestion
What are the three regions of the small intestine?
duodenum
jejunum
ileum
4-6 metres long, highly folded, large SA
Where in the GI tract does the most absorption take place?
Small intestine
How many strata of folding Is there in the small intestine?
3
How long is the large intestine?
1.5m in length
What does the large intestine remove?
WATER, SALTS, SUGARS, VITAMINS
What are the 5 parts of the large intestine?
1st Cecum 2nd Ascending colon 3rd Transverse colon 4th Descending colon 5th Sigmoid colon
What do Peyers patches do?
Local immune protection - areas of lymphoid tissues
What are long reflexes in the GI system?
Occur with external stimuli (sight and smell of food)
Involves CNS
Alters activity of ENS
it causes changes in motility and secretion
What are short reflexes in the GI system?
Internal stimuli (i.e. molecules in lumen)
ENS
Local neural circuits
Causes: changes in motility and secretion
What structures control movement through the tract?
Sphincters
What are the names of all the sphincters in the GI tract
Upper oesophageal
Lower oesophageal
Pyloric
Ileocaecal
Internal and external anal
What is peristalsis?
The contractive and relaxing movements of muscles in the Gi tract causing movement
Relaxation of longitudinal muscle- contraction of circular muscle
Contraction of longitudinal muscle- inhibition of circular muscle
What is peristalsis mediated by?
Neurones in the myenteric plexus
What stimulates peristalsis to occur
Distension by the bolus of food - oral contraction, aboral (moving away from the mouth) relaxation
What is Hirschprungs disease?
Congenital disorder
All or part of colon has no innervation
1:5000 children affected
Surgical removal of the colon
What are enteroendocrine cells?
Intestinal ‘taste’ cells
sense luminal contents and respond via release of peptide transmitters and hormones (act as chemoreceptors)
How many hormones and paracrine hormones are involved in the GI tract?
in excess of 22
secreted by enteroendorine cells in the mucosa
What is the negative feedback mechanism that controls luminal contents?
Hormones detect the luminal contents
stimulate secretions/motility etc
change in luminal contents reduces stimulus, hormone activity adjust
Describe motility of the stomach
- fasting state
- meal enters, LOS, fundus and body relax, allows expansion
- peristalsis begins in the middle pushing towards pylorus (end bit of antrum), mixing occurs in the antrum
- ‘retropulsion’
5. antral systole = peristaltic wave pushes contents back into body some chyme (the pulpy acidic fluid which passes from the stomach to the small intestine, consisting of gastric juices and partly digested food) moves into duodenum
What 3 things does the stomach act as?
Reservoir to store food
preparatory chamber - break down injected materials
emptying regulator - responds to feedback from duodenum. controls rate of release of calorie, H+ and particles into the duodenum.
What is chyme?
the pulpy acidic fluid which passes from the stomach to the small intestine, consisting of gastric juices and partly digested food.
Describe how peptic ulcers form
Break in mucosal barrier exposing underlying tissue to corrosive action (acid, proteases)
Why do solid empty slower than liquids?
Lag due to time to reduce particle size (1mm diameter)
liquids empty 2-3 minutes faster
What are the symptoms of gastric ulcers?
Abdominal pain
Bloating
Nausea/vomiting
Bleeding- haemorrhage and anaemia
Why do gastric ulcers form? - endogenous and exogenous factors
Endogenous Factors
Anxiety
Parasympathetic output (Ach, Gastrin) →↑acid
Stress
Sympathetic output (Ad) → ↓ HCO3/mucus
Exogenous Factors
Diet
Alcohol - damages cells, stimulates parietal cell
Coffee – stimulates parietal cell
Non-steroidal anti-inflammatory drugs (NSAIDs)
↓prostaglandin production →↓inhibition of acid
What bacteria can cause gastric ulcers?
Helicobacter pylori
What bacteria can cause gastric ulcers?
Helicobacter pylori - release proteases and endotoxins which break down stomach lining tissue
What ducts does the gall bladder and pancreas use for secretions?
Bile and pancreatic ducts
How much of the pancreas is made up of exocrine and endocrine glands and what are they and what do they secrete?
Exocrine - 86% - Acinus
secrete water, ions, bicarbonate (neutralises duodenal contents to prevent damage and ph for enzymes) and enzymes for digestion
Endocrine 2% - islets of langerhands - a cells (glucagon), b cells (insulin)
What is an exocrine gland?
glands that produce and secrete substances onto an epithelial surface by way of a duct. Examples of exocrine glands include sweat, salivary, mammary, ceruminous, lacrimal, sebaceous, and mucous
What is an endocrine gland?
glands of the endocrine system that secrete their products, hormones, directly into the blood rather than through a duct.
What do duct cells secrete and how does this help within the small intestine?
Duct cells secrete a watery, bicarbonate-rich fluid which flush the enzymes through the ducts and play a pivotal role in neutralizing acid within the small intestine.
Which ducts receive secretions from acini?
Intercalated ducts - flattened cuboidal epithelium extends into the lumen of the acinus to form centroacinar cells
Which ducts receive secretions from intercalated ducts?
Intralobular ducts - cuboidal and seen within the lobules
Which ducts transmit secretions from intralobular ducts to the major pancreatic duct?
Interlobular ducts - found between lobules
Where does the main pancreatic duct receive secretions from?
The interlobular ducts
Which type of duct is not present in the pancreas?
Striated ducts
Which enzymes are responsible for the digestive function of the pancreas?
Digest proteins (acinar cells secrete): Trypsinogen - trypsin Chymotrypsinogen - chymotrypsin Proelastase - elastase Procarboxypeptidase - carboxypeptidase
Lipase and phospholipase- Fats
Nucleases- Nucleic acids
α-amylase- Carbohydrates
Which cells secrete, bicarbonate, water and ions??
Ductal cells and centroacinar cells (extension of the intercalated duct cells into each pancreatic acinus)
What is cholecystokinin?
a hormone which is secreted by cells in the duodenum into the blood stream in response to proteins and fats in chyme and stimulates the release of bile from the gallblader into the intestine and the secretion of enzymes by the pancreatic acinar cells.
What is Secretin?
A hormone produced by the S cells of the duodenum which is stimulated by HCL in chyme to be released into the blood (pH <5) .
Secretin helps regulate the pH of the duodenum by (1) inhibiting the secretion of gastric acid from the parietal cells of the stomach and (2) stimulating the production of bicarbonate from the ductal cells of the pancreas
What are some of the functions of the liver?
Protein synthesis
Storage - triglycerides, glycogen, some vitamins (A)
Gluconeogenesis
Toxins - conjugation, breakdwn
Bile synthesis and secretion of bile acids and bilirubin
What is bilirubin?
an orange-yellow pigment formed in the liver by the breakdown of haemoglobin and excreted in bile
Where is bile stored?
Gall bladder
What are the main functions of bile?
Adequate pH - enzymes in the SI work best in alkaline conditions
Facilitate fat digestion/ emulisification
Excretion of waste products (cholesterol/bilirubin) by secretion into the bile
What is the composition of bile?
Water and ions- alkali
Bile acids- digestion and absorption of dietary fats (micelle formation) 70%
Proteins- protect against infection
Bile pigments- breakdown products of hemoglobin (bilirubin)
Organic molecules
Cholesterol (4%)
Phospholipid- Lecithin (20%)
What is the function of the gallbladder?
Alters bile composition and delivery:
absorption of Na, cl, water - concentrates the bile
secretion of H+ - neutralise alkaline mucin and protect surface epithelium
storage of bile
contracts and delivers the bile (cephalic 20% via Acetycholine, intestinal phase 80% CCK)
How is bile delivery controlled? (hormones)
Secretin stimulates secretion
CCK - stimulates release of bile by relaxing sphincter of Oddi and contracting gall bladder
What are gall stones?
Calcified stones made up of cholesterol, bilirubin and calcium
What are the main causes of gallstones?
Genetics Body weight Decreased mobility of gall bladder Diet Other diseases (cirrhosis, sickle cell)
Why does the microvilli have a large surface area?
Large number of tiny projections on the surface of small intestinal epithelial cells increases the surface area for nutrient absorption from the lumen
What does the glycocalyx do?
Unstirred layer on top of microvilli helps molecules to stay in the surface once absorbed
Name some brush border enzymes
Maltase, lactase, sucrase, dipeptidases
What type of transport is the glucose/galactose carrier?
Co-transport - Na dependent
energy needed to maintain Na gradient (secondary active transport)
What type of transport moves fructose into the cell?
GLUT2 carrier - facilitated diffusion
Where do the transported carbohydrates in the small intestine go to?
capillaries –> hepatic portal vein –> pass through liver
What are the 3 places of protein digestion in order? What enzymes act in these places and what is produced?
stomach
Gastric pepsin
Protein-polypeptide–> small peptide
duodenum
Pancreatic proteases
Protein- polypeptide –> small peptides and amino acids
brush border
Peptidases
Large peptides —> small peptides and amino acids
What type of transport takes small peptides and free amino acids into a cell?
Active transport
How are free amino acids moved into capillaries?
Facilitated diffusion
What do lipases digest?
Lipids into monoglycerides, fatty acids, glycerol in the pancreas
In what form are the lipids transported across the unstirred layer in the small intestine?
Micelles
What are triglycerides combined with to form chylomicrons within cells?
Cholesterol, protein, phospholipids
Where do chylomicrons ultimately end up
Diffusion into lacteals
Return to systemic circulation via thoracic lymph duct
What are three reasons malabsorbtion can occur?
Absent or defective digestive enzymes
Defects in transporter proteins
Diseases or infections of small intestine
What are the symptoms of malabsorption?
steatorrhea (frothy greasy stools), diarrhoea, weight loss
What are some examples of conditions where malabsorption occurs?
Lactase deficiency - lactose intolerance
Coeliac disease – abnormal immune response to gluten – loss of mucosal epithelium
Pernicious anaemia – malabsorption Vit B12 in ileum due to antibodies to intrinsic factor
What are tenia coli?
three separate longitudinal ribbons (taeniae meaning ribbon in latin) of smooth muscle on the outside of the ascending, transverse, descending and sigmoid colons.
What are Haustra?
small pouches caused by sacculation (sac formation), which give the colon its segmented appearance
What type of cell is there a high concentration of in the large intestine?
Goblet cells
What are the main functions of the large intestine?
High mucus secretion
all absorption by diffusion
efficient water reabsorption (aided by cl- absorption in exchange for hco3-)
Hco3= buffers acid produced by bacterial fermentation (indigestable products)
absorbing essential vitamins produced by gut bacteria
converts food into faeces
Which part of the GI tract has the most gut flora?
The colon
What essential nutrients are produced by gut bacteria?
Folic acid
vitamin K
b12
biotin
thiamin
short chain fatty acids
Where does dietary fibre mainly come from?
The indigestible portion of plant foods
What is the role of dietary fibre?
Motility - decreases gastric emptying in the stomach, increases motiliy of colon and intestines
adsorption - holds water, slows absorption of enzymes and nutrients
colonic bacterial substrate
prevention and treatment of constipation, haemorrhoids
reduces risk of colon cancer/
What are the sources of gastrointestinal gas?
Swallowed air, result of neutralisation of acid and bacterial metabolism, diffusion from blood (small). bacterial fermentation
gases - hydrogen, methane (ammonia, hydrogen sulphide, indole, skatole, volatile amines)
Describe mechanisms responsible for expulsion of GI contents via the mouth
Reversal of peristalsis
GI tract as a trigger for vomiting
What is the net absorption in % in the small intestine of protein, carb, fats?
100% protein
100% digestible carbohydrate
95% fats
Water, electrolyte (eg Na+, Cl-, Ca2+, Fe2+) vitamins (eg B12)
What is excreted?
indigestible fibre, bacteria, inorganic material, fat derivatives, desquamated cells, mucus
What is the normal balance between absorption and secretion?
absorption greater than secretion
What is diarrhoea?
Increase stool volume or increased frequency of defecation
What are the 4 types of diarrhoea?
- osmotic
- secretary
- inflammatory/infectious
- deranged motility
What is osmotic diarrhoea? What are the causes?
increased solutes in lumen causes water to move down concentration gradient from blood to lumen of the gut.
Less water is reabsorbed
causes - poorly absorbed substrate or a malabsorption disorder e.g. lactose intolernce
What is secretory diarrhoea? What are the causes?
Increased secretion of water into the lumen (exceeds absorption)
causes: Cholera toxin - opening of chloride channels can increase secretion of water,
hormomes, drugs, caffeine, laxatives, bile acid malabsorption
these cause some change in the function of the cells lining the gut
What is the mechanism of cholera producing diarrheoa?
cholera produces a toxin - binds to sugars on the surface of the cells - enters the cell (activated by cell RER)- binds to a G protein - activates adenylate cyclase - this produces cAMP which is a second messenger that can activate other processes - activates a chloride channel on the surface - pumps chloride ions into the lumen of the gut - which causes movement of sodium ion in to the lumen of the gut - water follows this osmotic gradient through the tight junctions in cells
What is secretory diarrhoea? What are the causes?
Increased secretion of water into the lumen (exceeds absorption)
causes: Cholera toxin - opening of chloride channels can increase secretion of water,
hormomes, drugs, caffeine, laxatives, bile acid malabsorption
these cause some change in the function of the cells lining the gut
What is inflammatory/infectious diarrhoea? What are the causes?
Bacteria can express proteases that damage the epithelial absorptive lining of the gut, less water can be absorbed
What is deranged motility diarrhoea? What are the causes
altered transit time through the gut hence less time for water reabsorption -
IBS, can result in constipation and diarrhoea
What is the purpose of segmented contractions in the colon?
- Retain material in the proximal colon
- Fermentation
- Water absorption - Mixing contents - allows things to be absorbed and bacteria to do its job - fermentation
How is defecation controlled? (nervous)
Faeces moved into the rectum, leading to distension. This activates stretch receptors in the lower sigmoid and rectum- afferent signals to the spinal cord
If it is convenient to defecate, voluntary motor nerves are inhibited allowing the external anal sphincter to relax
Symp and Parasymp- Stimulate contraction of the rectum and relaxation of the internal anal sphincter
What are two reasons for incontinence?
Pelvic floor damage
Pudendal nerve damage
What processes help continence?
Rectal accommodation (relaxation of colon/rectum) Sphincter closure
Why may there be failure in defecation?
Spinal injury
Outlet obstruction
What internal changes occur during defecation?
Colorectal contraction
Raised abdominal pressure
Sphincter relaxation
Internal (autonomic)
External (somatic)
What is emesis and why is it imporant?
The action of vomiting
protective mechanisms to prevent damage to GI tract and ingestion of contaminated/toxic substances
What are the detectors of toxin?
- -ingestion
Smell, sight, taste - Pre-absorbtion
Toxin detection in the lumen by
Mechanoreceptors and chemoreceptors
Causes neutralisation/expulsion (vomiting)
What are the detectors of toxin?
- -ingestion
Smell, sight, taste - Pre-absorbtion
Toxin detection in the lumen by
Mechanoreceptors and chemoreceptors
Causes neutralisation/expulsion (vomiting) - Chemoreceptive trigger zone - area postrema in the medulla
Outside of blood brain barrier- samples toxins in the blood
Induces nausea to prevent further ingestion and activates vomiting centres
What centre can be directly activated with emetics?
Area postrema in the medulla - contains chemoreceptive trigger zone recognises toxins in the blood
Give some examples of appropriate and inappropriate vomiting?
Food poisoning
Bowel obstruction
Bowel disease
Motion sickness
Cancer therapy
Pregnancy
What are signs of nausea?
Pallor Sweating Salivation Irregular breathing Increased heart rate Retching (several, increased force)
What movements in the stomach and abdomin occur during nausea and then emesis?
- Retrograde Giant contractions return intestinal contents to the stomach
- The proximal stomach relaxes to accommodate returning intestinal contents
- Antral motility (pushing back the other way) inhibited to prevent gastric emptying
- Expulsion caused by contractions of the diaphragm and abdominal wall
Describe the act of vomiting
Deep inspiration allows closure of glottis- protects respiratory tract
Air and saliva drawn into esophagus- protection and decrease esophageal pressure
Soft pallet elevated to prevent entry into nasopharynx
Expiration against closed glottis and abdominal contraction- increase intra abdominal pressure
Relaxation of the LOS (oesphogeal sphincter)
Passage of contents into esophagus
Relaxation of the UOS
Violent expulsive force- stomach and abdominal contraction
GI smooth muscle
Relaxation of all areas from gastric body to upper oesophagus
Violent contractions of gastric antrum pushing material up
Respiratory system
Slow deep inspirations to decrease oesophageal pressure
Skeletal muscle
Contraction of abdominal muscle
Retching
Upper oesophageal sphincter remains closed
Vomiting
Upper oesophageal sphincter opened
How is the GI tract stimulated for emesis?
Distension (stomach and duodenum)
Irritation of back of throat
Chemical or toxin
How is the chemoreceptor trigger zone stimulated for emesis?
Anaesthesia
Drugs
Radiation
How is the genitourinary system, hypothalamus/cerebellum and vestibular apparatus stimulated for emesis?
Injury/infection (geno)
stimulation or injury (hypothalamus/cereblleum)
motion sickness (vestibular)
What is the role of 5-HT (serotonin) in the emetic pathway?
produced by neuroendocrine cells lining the gut especially small intestine
respond to emetic signals e.g. radiation, injury, infection, toxins and release 5HT molecule that binds to its receptor 5HT3 in the nervous system - on vagus nerve
can also enter blood stream and act on chemoreceptor trigger zone
What are the three phases of the emetic reponse to anticancer chemo?
Anticipatory- Conditioned response (at the thought of receiving chemo)
Acute- Enterochromaffin cells release 5HT which acts on 5-HT3 on the chemoreceptor trigger zone
Delayed- Damage to epithelial/cell breakdown products evokes mediator release (including 5HT )
How do anti-emetics work?
blocking activation of the vomiting centre - chemoreceptor trigger zone
e.g. Ondanstron - 5HT3 antagonist
5-HT3 receptor antagonists have revolutionized treatment of nausea and vomiting in cancer patients.
What does the pancreas feature?
Acinar cells Centroacrinar cells Intercallated ducts Intralobular duct Islets of langerhans
Where are enzymes involved in protein degradation found?
Zymogen granules
Name some pancreatic enzymes
Digest proteins: Trypsinogen - trypsin Chymotrypsinogen - chymotrypsin Proelastase - elastase Procarboxypeptidase - carboxypeptidase
Lipase and phospholipase- Fats
Nucleases- Nucleic acids
α-amylase- Carbohydrates
What do acinar cells produce?
a small amount of protein (enzyme rich) fluid
Passes through the intercalated duct- ductal cells and centraacinar cells secret bicarbonate, water and ions
