GI 1-6 Flashcards
What changes does digestion make to food?
Sterile
Neutral
Isotonic
What state does digestion change food to?
Solution of small sugars, amino acids, lipids in very small peptides and other small molecules
What does the body excrete?
Residues from food
Debris from the gut
Materials specifically excreted via liver to gut
How does the body break down food?
Physically to release large molecules
Chemically to release small molecules
Define chyme.
The semifluid mass of partly digested food expelled (slowly so as not to overwhelm) by the stomach into the duodenum. Generally sterile due to stomach acid.
Why must chyme be diluted?
Very hypotonic and acidic so must be made isotonic and neutral so as not to damage the rest of the GI tract.
What is mastication?
Chewing.
What is the purpose of saliva?
Protects mouth
Lubricates food for astication and swallowing - wet, mucus
Starts digestion - enzymes (esp. sugars)
How does saliva protect the mouth?
Wet
Bacteriostatic
Alkaline
High calcium
Why is the formation of a bolus important?
streamlined allowing for rapid, easy transport from mouth to stomach for storage.
How does the stomach accomodate storage and digestion?
Relaxes to accomodate food - receptive relaxation
Contracts rhymically and periodically to mix and disrupt - exposes chyme to secretions
Secretes acid and proteolytic enzymes to break down tissues and disinfect
What processes occur in the duodenum/jejunum?
Dilution and neutralisation - makes it safe to pass through the rest of the system
Osmotically draws water in from ECF to make it isotonic
Pancreas and liver secrete alkali (HCO3) to neutralise the acid
enzymes and bile salts to complete digestion
What are some of the products of digestion?
Amino acids from polypeptides
Monosaccharides from polypeptides
Break down and reform lipids
Break down nucleic acids
How is the surface area of hte intestine increased?
Brush border - villi
How are molecules absorbed in the small intestine?
Actively/passively
Often coupled to Na absorption
Where are absorbed molecules from the small intestine transported to?
Liver by hepatic portal vein
What is absorbed in the large intestine?
Water and some electrolytes
Very slow process
Where in the large intestine do faeces accumulate?
Descending and sigmoid colon
What are the 3 main processes of the GI system?
Secretion
Motility
Absorption
Why is it important to maintain a balance between secretion and absorption?
Imbalance will cause considerable loss of water and electrolytes - dehydration and electrolyte disturbance. Mostly from body fluids rather than ingested food adn water.
What are the 3 methods of control of the body for motility and secretion?
Neural
Paracrine
Endocrine
What is the neural control of the gut?
Somatic motor system for ingestion and excretion
Autonomic nervous system the rest - mostly parasympathetic. Coordinates both secretion and motility. Range of neurotransmitters. Gut is full of nerve cell bodies in the walls - plexuses
What is paracrine control? Give some examples in the gut.
Chemical messengers diffusing locally - NOT through blood
Histamine in stomach
Vaso-active substances to alter blood flow
How are hormones used in GI?
Secretion of stomach acid
Alali secretion from liver and pancreas
Enzyme secretion
All peptides in structurally related families
What does the mouth do?
Way into the GI tract - preliminary disruption of food (mastication), formation of bolus, swallowing
How is the mouth protected?
Teeth and oral mucosa
What do the different teeth do?
Incisors cut
Molars crush
What is the muscle of mastication?
Masseter. Innervated by branch of the trigeminal nerve
What is the function of saliva?
Lubricates and wets food
Starts digestion of carbs
Protects oral environment
How does saliva protect the oral environment?
Keeps mucosa moist
Washes teeth
Maintains alkaline environment - neutralises acid produced by bacteria
High calcium content
What are the consequences of poor saliva production?
Zerostomia (dry mouth)
Can still eat food provided it is moist but teeth and mucosa degrade very quickly
What are the constituents of saliva?
Water (hypertonic)
Electrolytes - Na and Cl in lower conc than plasma, Ca, K and I ususally at higher conc than plasma
Alkali - HCO3 in higher conc than plasma
Bacteriostats
Mucous - mixture of mucopolysaccharides
Enzymes - salivary amylase
What type of glands are salivary glands?
Ducted exocrine
3 paired glands - parotid, sub maxillary and sub-lingual
Describe exocrine glands
Blind ended tubes
Acini lined with acinar cells
Connected system of ducts lined by duct cells
Describe the secretion of the parotid gland
Watery, rich in enaymes but little mucus. Serous saliva
25% of total saliva
Describe the secretions of the sub-lingual glands
Viscous
No enzymes
Lots of mucus
(Mucous saliva)
5% of total saliva
Describe the secretions of the sub-maxillary glands.
All components of saliva - mixed serous and mucous
Gland is made up of mixture of serous and mucous acini leading to common ducts
70% of total saliva
How is a hypotonic saliva created?
Made from more concentrated extra-cellular fluid
No cellular mechanism for secretion of water so a more concentrated solution is secreted and then solute taken out
What determines the volume adn composition of saliva?
Volume - acinar secretion
Composition - ductal secretion. Has a max rate of modification except for HCO3
Describe resting saliva
Low volume
Very hypotonic
Neutral or slightly acid
Few enzymes
Describe stimulated saliva.
High volume
Less hypotonic than resting
More alkaline than resting
Lots of enzymes
What is the mechanism of acinar secretion?
Not ultra-filtration
Active secretion of ions - Cl
Water and other ions follow passively
How is salivary secretion controlled?
Largely nervous
ANS - sympathetic, superior cervical ganglion and parasympathetic, Glossopharyngeal (9th) and Otic ganglion
Where is the afferent informatino of the parasympathetic outflow to the salivary glands from?
Moth and tongue - taste receptors, especially acidic
Nose
Conditioned reflexes - pavlov’s dogs
What are the affects of parasympathetic outflow on saliva?
Releases acetyl choline
Acts on acinar cells to promote formation of primary secretion
Acts on duct cells to promote HCO3 secretion
Muscarinic receptors - blocked by atropine like drugs
Co-transmitters stimulate extra blood flow
Sympathetic stimulation reduces blood flow - dry mouth
What stimulate swallowing?
Bolus moving to pharynx
What are the phases of swallowing?
Voluntary phase
Pharyngeal phase
Osophageal phase
What happens in the voluntary phase of swallowing?
Separation of the bolus and it moves to the pharynx
What happens in the pharyngeal phase of swallowing?
Pressure receptors in the palate and anterior pharynx which are afferent to the brain stem swallowing centre which:
Inhibits respiration
Raises the larynx
Closes the glottis
Opens the upper oesophageal sphincter
Describe the oesophageal phase of swallowing
Upper third is voluntary
Lower two thirds is smooth muscle
Rapid peristaltic wave coordinated by extrinsic nerves
Transit time to stomach about 9 seconds, lower osophageal sphincter opens
What might cause dysphagia?
(problems swallowing)
Motility problems - achalasia
Obstruction or compression of the oesphagus - tumours
Swallowing is absent in brain death and must be checked after head injury/surgery
Why are the abdominal muscles (Rectus abdominous) not one long muscle?
Short muscles more efficient
Where is mcburneys point?
2/3rds of teh distance between the umbilicus and ant sup iliac spine
Define referred pain
Pain perceived at a site distant from the site causing the pain
What is somatic referred pain?
Pain caused by a noxious stimulus to the proximal part of a somatic nerve that is perceived in the distal dermatome of the nerve
Why does visceral referred pain occur?
In the thorax and abdomen, visceral afferent pain fibres follow sympathetic fibres back to the same spinal cord segments that give rise to preganglionic sympathetic fibres. The CNS preceives visceral pain as coming from the somatic portion of the body supplied by the relevant spinal cord segment(s).
What causes visceral pain?
Not superficially sensitive eg. Touch, burning, cutting, crushing
Ischaemia, abnormally strong muscle contraction, inflammation adn stretch does.
Where does midgut pain refer to?
Umbilicus
What is a hernia?
A protrusion of the abdominal contents through the abdominal wall
Why is the transversalis fascia so important?
Stops us getting a direct hernia
What are the common types of hernia?
Femoral
Inguinal
epigastric
Umbilical
Richters
Spiliegan
incisional
What are risk factors for hernias?
Age
Male
Smoker
What is Hesselback’s triangle?
Area where direct hernias are common in between the abdominal muscle, inguinal ligament and inferior epigastric artery
Where do indirect hernias occur?
Deep inguinal ring within the diverging arms of the transversalis fascial sling
Where do femoral hernias occur?
Below the inguinal ligament
What is the most common hernia in women?
Indirect inguinal but femoral is more common in women than men
What is a divaricatioin of recti?
separation of the rectis abdominis muscle
What is a Richter’s hernia?
part of the bowel strangulates through the hernia so no obstruction but painful
What is a spigelian hernia?
hernia at the junction where the internal/external obliques meet the rectis muscle and the posterior sheath stops
Why are hernias operated on?
Painful
worrying - cosmetic
bowel obstruction
risk of strangulation (1%) - mortality over 15%
How are hernias repaired?
Try and obtain primary closure
Tension free
Laproscopic reinforcement
Mesh
What is the purpose of the stomach and why is it necessary?
Stores food as we ingest food faster than we can digest it
Disinfects food to prevent disease
Breaks food down into chyme
Why does the stomach need protection and how is this provided?
It is designed to destroy biological material but it is itself biological material so protects itself with mucus and alkali
What does the stomach secrete?
Attack - Hydrochloric acid and proteolytic enzymes
Defence - Mucus and HCO3-
Where do stomach secretions come from?
Gastric pits:
Chief cells - enzymes
Parietal/oxyntic cells - acid
Neck cells - mucus
Endocrine cells - gastrin
Describe the mechanism of secretion of acid in the stomach
Made from slightly alkaline solution. 1 mol of alkali must be produced for every mol of acid- acid into stomach, alkali into blood
Cells split water into H+ and OH- ions.
OH- combines with CO2 to produce HCO3-
H+ produced by mitochondria
How are parietal cells adapted for acid production?
Have lots of mitochondira which produce H+ at high rate. H+ cannot accumulate in the cells so the sells have canaliculi - invaginations in the cell wall which have proton pumps - expel H+ against high conc grad.
This requires lots of energy
What happens to blood pH when we eat?
Increases because alkali is made in the stomach at same rate as acid
What factors can act on the parietal cell to stimulate acid secretion?
Gastrin
Histamine
Acetyl Choline
Describe gastrin and explain how it acts in the stomach.
Hormone secreted by G-cells in the stomach
Polypeptide, main form 17 aa long
Bind to surface receptor on parietal cell
Stimulates acid and intrinsic factor secretion via second messenger pathway
How does histamine act in ithe stomach?
Released from mast cells
Binds to H2 surface receptor on parietal cell
Stimulates acid secretion via c-amp
Describe the action of acetyl chomine on the stomach
Released from post ganglionic parasympathetic neurones
Acts on muscarinic receptors on parietal cell
Stimulates acid secretion by second messenger pathway
What affects gastrin secretion?
Stimulated by:
Peptides
Acetyl choline from intrinsic neurones
Inhibited by:
Low pH in stomach - feedback control
What stimulates mast cells?
Gastrin
Acetyl choline
Causes it to secrete histamine. This is therefore an amplifier action.
What causes the release of acetyl choline to parietal cells?
Distension of the stomach
CNS
What are the phases of control in the stomach?
Cephalic phase
Gastric phase
Intestinal phase
What is the cephalic phase and how does the control work?
Detecting and ingesting food
Autonomic stimulation - Ach stimulates parietal cells directly and via histamine
What is the gastric phase of control?
Food reaches stomcha - buffers stomach acid so pH rises (disinhibits gastrin)
Stomach distends - stimulates intrinsic nerves (release Ach)
Initial digestion releases peptides - stimulates gastrin release
Histamine release stimulated by gastrin and Ach
What is the intestinal phase of control?
Stomach begins to empty
Chyme stimulates release from intestines of hormones which antagonise gastrin
Accumulation of acid in empty stomach inhibits gastrin secretion
Stomach pH low betwen meals - can aggravate ulcers and cause night pain
How are the stomachs defence mechanisms controlled?
Mucus and alkali secretion stimulated by prostaglandins
Promoted by most factors stimulating acid secretion
Defences match the attack
How might the stomachs defences be breached?
Alcohol dissolves the mucus
H. Pylori
NSAIDS - inhibit prostaglandins therefore reduce defences. Some, like aspirin, converted into non-ionised form by stomach acid, pass into cells and then re-ionise
Breaching results in peptic ulcers
How is acid secretion reduced?
Histamine receptor antagonists - H2 - cimetidine
Proton pump inhibitors - Omeprazole
Also treat ulcers by eliminating H. Pylori with antibiotics
Describe the stomachs motility.
Relaxes to accomodate food
Contracts rhythmically to break down large particles
Delivers chyme slowly to the duodenum
How does receptive relaxation occur?
Neural reflex
Triggered by swallowing
Efferent pathway via vagus
Tension in resting stomach wall is ‘actively’ relaxed
Pressure in stomach does not increase as it fills - limits reflux
So can consume large meals (but not if vagus nerve damaged
How deos rhythmic contraction occur?
Stomach has longitudinl and circular muscle
Driven by pacemaker in cardiac region
Fires about 3 times a miute
Wave of peristalsis spreads towards antrum accelerating as it goes
This initially drives all stomach contents ahead of it. Chyme overtakes larger lumps as it accelerates and the lumps are driven back to the fundus
Small squirt ejected then wave reaches the pylorus and shuts it. Rest of chyme returns to stomach
How is gastric emptying controlled?
Volume of each squirt affected by rate of acceleration of peristaltic wave wiche is affected by hormones from intestine
Gastric emptying slowed by fat in duodenum, low pH in duodenum and hypertonicity in duodenum
Rate of stomach emptying matched to rate of digestion
What are complications of gastric/duodenal ulceration?
Bleeding
Perforation
Gastric obstruction
What is gastritis?
Histological inflammation of the stomach
What is a gastric ulcer?
Broken down the mucous bicarbonate and epithelial barrier
What is the cause of gastritis?
Helicobacter pylori - produces inflammatory response
Motile, microaerophilic, urease producing bacteia
Adheres to gastric mucosa and produces cytotoxins
Always associated with ulcers
Transmission by oral-oral route/feacal-oral route
What does the upper 2/3 of the stomach secrete?
HCL and pepsinogen
What does the lower 1/3 of the stomach secrete?
Mucus and gastrin
What is dyspepsia and what is the difference between functional and non-functional dyspepsia?
indigestion - impaired digestion. Pain in the upper abdomen and premature fullness. Ofen associated with bloating, belching, nausea and heartburn. May be caused by gastritis or gastroesophageal reflux disease.
Functional dyspepsia is not associated with ulcers.
What enhances acid secretion in the stomach?
TNF, IL1 IF stimulate gastrin secretion
TNF decreases antral D cells which are responsible for shutting off acid secretion
What increases mucus secretion?
Cytokines
What effect does vitamin C have on gastric cancer cells?
Inhibits their growth
What are the causes/risk factors of ucers?
Acid
Diest
Smoking
Alcohol
Stres
ZE syndrome
Helicobacter pylori
NSAIDs
What is ZE syndrome?
Caused by a non-beta islet cell, gastrin secreting tumour of the pancreas that stimulates the acid secreting cells of the stomach to maximum activity with consequent gastrointestinal mucosal ulceration
How does a bacterium that only colonises gastric mucosa cause duodenal ulceration?
Antral helico pylori colonisation causes and increase in gastrin production which then increases the parietal cell acid production. The duodenal cap is damaged and gastric metaplasia gastric mucosa. Helicobater colonise the gastric mucosa of the duodenum and the immune response causes duodenitis which can lead to ulceration
What need to be considered pharmacologically when looking to manage ulceration?
Bacterial niche
Antibiotic resistance
Compliance
Testing for eradication
Treatment in the elderly
PPI-Hp-stomach interations
Describe the stages of mucoal change leading to cancer of the stomach from gastritis.
H. pylori chronic active non-arophic gastritis -> multifocal atrophy -> intestinal metaplasia -> dysplasia -> carcinoma
How is chyme “conditioned?
Acidtity corrected by HCO3- secreted from the pancreas, liver and duodenal mucosa
Hypertonicity corrected by osmotic movement of water across the duodenal wall
Digestion is completed by enzymes from the pancreas and small intestinal mucosa and bile acid from the liver
What does the exocrine pancreas secrete?
Alkaline juice
Enzymes :
- Proteases
- Amylases
- Lipases
What proteases are released from the exocrine pancreas?
Trypsin
Chymotrypsin
Elastase
Carboxypeptidase
What is teh exocrine pancreas made up of?
Acini and ducts:
Acini secrete enzymes, ducts secrete alkaline juice
Describe acinar secretion.
- Enzymes synthesised on ribosomes - mostly as inactive precursors
- Packaged into condensing vacuoles by Golgi comples
- Form zymogen granules secreted by exocytosis
- Activated in intestine by enzymatic cleavage
- If pancreas is damaged (eg. pancreatitis) enzymes (amylase - easy to assay) appear in blood
How is acinar secretion stimulated?
Hormone. Cholecystokinin (CCK) released from duodenal APUD cells. Sensitive to Hypertonoicity and fats -> release CCK (intestinal phase)
Same receptors also stimulated by Gastrin
Vagus nerve also stimulates by release of acetyl choline (cephalic phase)
Describe ductal secretion from the pancreas.
Secrete HCO3-
Present in blood at elevated concentration because of gastric secretion of acid
Celliular mechanism loke other HCO3- secretion (Na-K-ATPase coupled, transported as H2O and CO2)
What stimulates duct secretion?
Secretin released from jejunal cells in reponse to low pH. Action of secretin facilitated by CCK
What is the function(s) of the liver?
Blood:
- Energy metabolism
- Detoxification
- Plasma proteins
Gut:
- Secretion of bile - 0.25-1l/d. - bile acids and alkaline juice for digestion, excretion of bile pigments - prevents damage of kidneys
Describe the blood supply to the liver
Portal blood supply- In through hepatic portal vein from gut to central vein through sinusoids surroundsd by hepatocytes which fulfill the blood facing function
Also has an arterial supply of oxygenated blood
Describe the structure of the liver in relation to its function for the gut.
Bile is secreted into blind ended canaliculi by hepatocytes (bile acid dependent) and duct cells (bile acid independent) and flows to the bile duct.
What is the difference between bile acid dependent and independent secretions in the liver?
Dependent - from hepatocytes, contains bile acids and pigments
Independent - Secreted by duct cells, contains alkaline juice like that from pancreatic duct cells
How are bile acids related to cholesterol?
Cholic acid
Chenodeoxycholic acid
Travel in bile as micelles - bile acid + cholesterol + phosphlipids
Why is lipid digestion complicated and how does bile acid help with this?
Hydrophobic nature:
- Tend to for mlarge globules as stomach acid breaks down natural emulsions
- Low surface area for enzymes to act
Bile acids emulsify fat into much smaller globules
- increase surface area for lipase to cleave fatty acids and glycerol
- Colipase links bile acids and lipase to spread them over surface
How do released fatty acids form micelles?
- Polar groups of bile acids on outside
- Hydrophobic fatty acids within
- 4-6nm in diameter (20 lipid molecules)
- Need bile acids to be above a critical concentration to form
- Also sequestre cholesterol, fat soluble vitamins and phospholipids
What are micelles?
Vehicle to carry hydrophobic molecules through aqueous luminal contents into unstirred layer next to epithelial cells. Released slowly and enter cells by diffusion
Fatty acids etc used to re-synthesise lipids in epithelial cells
Exported to lymphatics as chylomicrons (lipid with polar protein and phospholipid coat)
Describe the route of bile acids through the body
Enterohepatic circulation
- Released into the gut lumen after fatty acids etc absorbed
- continue to terminal ileum
- Absorbed actively by epithelium of terminal ileum
- Return in hepatic portal blood to hepatic sinusoids
- Hepatocyts take up actively and resecrete into canaliculi
Why might bile acids not return to the liver?
Some are unconjugated by bacterial action in the gut and lost
What are the problems with the recovery of bile salts and how are they overcome?
- Bile acids return to the liver in beteen meals
- Secreted by canalicular cells well before needed next (cannot be stored in liver)
- Stored in the gall bladder
- Volume stored reduced by concentration - transport of salt and water across gall bladder epithelium
- Concentration process increases risks of precipitation - gall stonesW
How is bile removed from storage?
Cholecystokinin secreted by duodenum in response to gastric emptying -> Stimulates contraction of gall bladder muscle, ejecting concentrated bile acids together with enzymes from pancreas and alkali from pancreas and liver in response to secretin
What is steatorrhoea?
Bile acids or pancreatic enzymes are not secreted in adequate amounts (malabsorption of fat) -> fat appears in faeces (pale, floating, foul smell)
What is caused if bilirubin accumulates in the blood?
Jaundice
What is the excretery route of bilirubin?
Breakdown product of haemoglobin conjugated in liver, secreted into bile and excreted in faeces
What are the common causes of jaundice?
- Pre-hepatic jaundice occurs when a condition or infection speeds up the breakdown of red blood cells. This results in an increase in bilirubin levels in the blood and triggers the symptoms of jaundice.
- Intra-hepatic jaundice occurs when damage to the liver, either as the result of infection or exposure to a harmful substance, such as alcohol, disrupts the liver’s ability to process bilirubin.
- Post-hepatic jaundice is triggered when the bile duct system is damaged, inflamed or obstructed, which results in the gallbladder being unable to move bile into the digestive system.
