GI physiology Flashcards
Role of mouth and pharynx
chops and lubricates food, starts carb digestion, delivers food to oesophagus
Where is saliva secreted from
Salivary glands
Role of oesophagus
propels food to stomach using peristalsis
role of stomach
stores/churns food, carb digestion, initiates protein digestion using protease and pepsin, regulates chyme delivery to duodenum
small intestine
principle site of digestion and absorption of nutrients
large intestine role
reabsorb fluids and electrolytes, stores faecal matter before delivery to rectum
rectum and anus role
regulated expulsion of faeces
4 main roles of the alimentary canal
motility, secretion, digestion, absorption
what are layers of mucosa
1) mucus membrane
2) lamina propria
3) muscularis mucosae
layers of submucosa
1) connective tissue
2) larger blood and lymph vessels
3) glands
4) submucous plexus - neurone network
layers of muscularis externa
1) circular muscle layer
2) myenteric plexus - between two muscle layers
3) longitudinal muscle layer
Layers of serosa
connective tissue
Explain the electrical activity in smooth muscle cells
The small intestine(don’t need an action potential in the stomach) smooth muscle cells are all connected by gap junctions which allows current to flow between all the cells called the interstitial cells of Cajal (ICCs). These act as pacemakers and together form action potentials modulated by neuronal, hormonal and mechanical stimuli. Once the action potential is reach a slow and synchronous wave goes between all the cell. There will only be a contraction if the slow wave amplitude is high enough to reach threshold. The longer it maintains threshold, the longer the contraction
excitatory influences vs inhibitory influence
These are part of the parasympathetic system. Excitatory lead to increased gastric, pancreatic and small intestinal secretion and increase blood flow and smooth muscle contraction whereas inhibitory influences stop digestion by relaxing sphincters and stomach
What does the myenteric plexus regulate
motility and sphincters
what does the submucous plexus regulate and where is it found
epithelia and blood vessels and in the submucosa
what is a short reflex
Involves the ANS and stimulates a post-ganglionic fibre which then sends a signal right back to the GI wall. For example distension will cause inhibition of muscle activity in adjacent areas
What is a long reflex
a long reflex involves the CNS like a vago-vagal reflex that has both sensory and motor neurones. The gastroileal reflex is where in increase in gastric activity then increases propulsive activity towards the terminal ileum
What is released when longitudinal muscle relaxes and when does it relax
relaxes behind the food bolus and releases VIP and NO
What is released when longitudinal muscle contracts
Ach and substance P
what is release when circular muscle relaxes
VIP and NO
what is released when circular muscle contracts and when does it
it contracts after the food bolus and released Ach and substance P
What is segmentation
rhythmic contractions of the circular muscle layer found in the muscularis externa
colonic mass movement
powerful sweeping contraction forcing faeces into rectum
migrating motor complex
sweeping contraction from stomach to terminal ileum a few times an hour
tonic contractions
sustained contractions like sphincters are at high pressures
how do sphincters work
usually a higher pressure in the distal organ keeps the sphincter closed and it will emit tonic contraction
what is luminal digestion mediated by
pancreatic enzymes into the duodenum
what is membrane digestion mediated by
enzymes situated at the brush border of epithelial cells
what are the two types of digestion
luminal and membrane
assimilation
overall process of digestion and absorption
what is the limitation to alpha-amylase
It cannot break down terminal alpha-4 linkages, and branch alpha-6 linkages or alpha-4 linkages that area adjacent to branch points
in the apical membrane, which monosaccharides need active transport and which need facilitated diffusion? and which mediators are used?
facilitated diffusion - fructose by GLUT5
active transport - glucose and galactose by SGLT1
How do monosaccharides exit the cell into the blood
through the basolateral membrane through facilitated diffusion through GLUT2
How is SGLT1 involved in rehydration therapy
Sodium is needed to work the SGLT1 so it moves into the cytosol so that glucose can move in as well and this attracts water into the cell since water follows sodium
What are the two enzymes that breakdown protein and where are they found
pepsin - in the stomach works best at low PH
pancreatic proteases- released from pancreas and activated in the duodenum
What do brush border proteases do?
further break down oligopeptides at the brush border
What do cytoplasmic peptidases do?
break down oligopeptides once they are in the cytoplasm
Difference between endopeptidase and exopeptidase
Digestive enzymes in the duodenum and endopeptidases break proteins down into oligopeptides whereas exopeptidase break down into single amino acids
How are do amino acids enter the cell?
Through difference amino acid transporters, some of which require sodium and some that don’t
how do oligopeptides enter the cell?
through H+ dependent co-transporters and are then further broken down in the cytoplasm
how do amino acids leave the basolateral membrane?
through Na+ dependent transporters
Which type of diabetes are you more at risk for if you are overweight
type 2
What are the different satiation signals?
CCK, peptide YY (PYY3-36), glucagon-like peptide 1 (GLP-1), Oxyntomodulin (OXM), obestatin
What are satiation signals released in response to?
Eating a meal to indicate to slow eating
Which satiation signals are released from the small intestine?
CCK, OXM, Obestatin
Which satiation signals are released from L cells?
PYY-36, GLP-1
What happens to insulin and leptin with obesity?
they stop telling the body to increase energy burn and to eat less
where is ghrelin released
released from the oxyntic cells in the stomach
What is bariatric surgery?
surgery that can be used for obesity treatment. A gastric-bypass surgery that allows up to 50% weight loss in a year and it is sustainable since less caloric intake
What causes the stomach to relax to accommodate for food?
the vagus nerve
which part of the stomach is food stored and which part is it churned
Stored in the fundus and ground in the antrum
what is secreted from the gastric glands?
gastric juice and they are in the gastric mucosa
Explain journey of food through stomach
1) relaxation of stomach by vagus nerve to accomodate for extra food
2) food enters the orad region where it starts being broken down by pepsin, HCL and salivary amylase
3) stomach contents are slowly propelled to caudad region with weak tonic contractions to allow time for HCL to work
4) gastrin contractions also slowed
5) minimal mixing as it moves down so that the salivary amylase can stay inside the food particles since when expose to HCl will be denatured
6) slow peristaltic contraction driven by slow waves moved the food towards the pylorus and some chyme gets through to duodenum
7) Then chyme rebounds because of velocity of contraction and goes back into body of stomach which mixes food - retropulsion
8) small particles mixed with chyme then move through every time
increase of vagus nerve activity and gastrin release do what to stomach
increase stomach emptying
how does the duodenum delay stomach emptying
neuronal and hormonal response
how does the hormonal response work
enterogastrones like CCK inhibit stomach contractions
what kinds of things influence the neuronal and hormonal response (3)?
fat - takes long to digest so would need to delay gastric emptying
acid- acid needs to be neutralised first so takes time for pancreas to produce the bicarbonate (if it is not neutralised the enzymes will not be working as well)
hypertonicity - need to be released slowly since if too much carb and proteins products they will draw water into the lumen instead of water being absorbed and can cause low bp
Where are glands in the stomach found?
In the gastric mucosa at the bottom of the pits in the surface
how deep do pits go?
from mucosa to submucosa
What does HCL do?
Activates pepsinogen to pepsin, denatures proteins and kills most organisms that are ingested with food
What is pepsinogen?
Precursor of the peptidase, pepsin and once pepsin is formed it can activated pepsinogen
What does gastroferrin do?
Bind Fe2+ so doesn’t become salt
What are the two ways that secretagogues work?
Direct – stimulate the parietal cell to secrete more hydrogen into lumen. Indirect – Ach and gastrin can stimulate histamine which will then act on parietal cell
Which pathway do Ach and gastrin use when acting on parietal?
PLC pathway
Which pathway does histamine and somatostatin act on
AC and cAMP
Which receptors does Ach act on for acid secretion?
M3 receptors
Which receptors does gastrin act on?
G cell receptors
What changes occur during the cephalic phase?
Vagus nerve stimulated to release Ach which directly activates parietal cells. Ach also stimulates gastrin and histamine release and it decreases the inhibitory effect of somatostatin on G cells by inhibiting D cells
How does food in stomach increase digestion?
Food buffers the PH so D cells are inhibited and amino acids stimulate G cells
Which cells stimulate histamine and gastrin respectively?
Enterochromaffin cells and G cells
How is acid secretion inhibited in the stomach after digestion?
Antral PH falls as food exits stomach so D cells starts again. Prostaglandin is secreted which reduces histamine and gastrin
Why is the digestion of fats difficult?
Because most fats like TAGs and cholesterol esters are insoluble or poorly soluble
What is the first step to breaking down fats before bile salts are involved?
Mechanical disruption by chewing and mixing in the stomach and small intestine break down the liquids into smaller droplets so that there is more surface area for lipases to act. These droplets are then coated in a multilamellar layer so that they do not join up again
What do bile salts do in fat digestion
Bile salts further digest these droplets and make them smaller and smaller. First turning them a unilamellar vesicle and then into a mixed micelle
What enzyme works in the stomach against fats?
Gastric lipase – breaks down some fats since short and medium chains are absorbed in the stomach
What stimulates both bile salt and pancreatic lipase release?
CCK
What could failure to release bile salts result in?
lipid malabsorption and vitamin deficiency of fat soluble vitamins
How is procolipase activated?
By trypsin
What does colipase do?
Binds to bile salts so that they do not block the lipase attaching to the TAGs
How do free fatty acids and monoacylglycerols enter the enterocytes?
They are first made neutral by adding a hydrogen and then can diffuse across the membrane
Where do chylomicrons drain back into the venous system?
At the left venous angle
Where is cholesterol picked up when it is absorbed?
It is picked up in clatherin coated pits where it attaches to NPC1L1 and then undergoes endocytosis
When calcium concentration is high, how is it absorbed?
It diffuses through gap junctions into blood
How much iron does the body contain
Approximately 3-5 grams
What does too little iron cause?
Microcytic anaemia
What does too much iron cause?
Excess iron can result in the production of hydroxyl radicals and hydroxide ions which are toxic for liver, pancreas and heart
What is the reduced state of iron called?
Fe 2+
What encourages the reduction of iron?
HCl, Vitamin C, gastroferrin from parietal cells, duodenal cytochrome B
How is iron transported across the cell?
Chaperone protein
Where is iron stored and what is it stored as?
Iron is stored in the cytoplasm as Fe3+ which is called ferritin
After iron leaves the cell, what enzyme oxidizes the iron back to Fe3+?
Ferroxidase
What causes hereditary chromatosis?
A defect in the HFE protein since that is what stops iron being transported to body if there is already too much
Where is B12 found and what is the recommended daily amount?
In food bound to proteins and daily amount is 6micrograms
Why does vitamin B12 have a complex absorbing pathway?
It needs to be efficient because it is only present in small amounts in the diet
Where is B12 ultimately absorbed and how?
Terminal ileum by endocytosis
How are fat soluble vitamins absorbed?
They passively diffuse into enterocytes where they are incorporated into chylomicrons and released into the lymph system and then venous system
Where are fat soluble vitamins stored?
Adipose tissue
How are water soluble vitamins absorbed?
Transport across membrane via Na+ dependent and independent transporters
what parts make up the large colon?
caecum, appendix, colon, rectum
what are the taeniae coli
longitudinal smooth muscle layer that is split into three parts
how are haustra formed
the activity of the taeniae coli and circular muscle layers that are slowly moving
what is the difference between the internal and external anal sphincter
the internal anal sphincter is thick and is controlled by the autonomic nervous system while the external one is surrounded by the skeletal muscle and is regulated by the somatic system
why is it important that the ileocaecal valve is one way
it is important that it prevents colonic contents like bacteria coming into the small intestine
where is the ileocaecal sphincter
several cm proximal to the valve
what controls the ileocaecal sphincter
positive resting pressure that relaxes when duodenum is distended and contracts when the ascending colon is distended
It is also under control from vagus nerve, sympathetic nerves and hormonal signals
where is the appendix attached to the colon
at the caecum via the appendiceal orifice
what three actions does the gastroileal reflex involve
- relaxation of ileocaecal sphincter
- increased contraction of ileum
- delivery of chyme from ileum to caecum
What are the main functions of the ascending and transverse colon?
absorbing sodium, chlorine, water and short chain fatty acids AFTER they have been fermented by the flora
secreting potassium, bicarbonate and mucus
what is the primary function of the descending colon
reservoir for storing contents, final drying stage before defeacation
What are the three types of cell in the large colon
surface epithelial cells (colonocytes), crypt cells and goblet cells
What is the function of epithelial cells?
absorb electrolytes and therefore also aid in water absorption
What is the function of crypt cells
secrete ions
What is the function of goblet cells in the large colon
secrete mucus to form a slippery surface gel and trefoil proteins which help stabilises mucus and help in host defense
describe haustration
haustration is the movement of the circular muscle which slowly (less frequent than segmentation) mixes content back and forward in the intestine allowing time for absorption
Describe mass movement, how often it occurs and what triggers it
simultanesous contractions of a large stretch of circular muscle throughout ascending and transverse colon that powerfully drives faeces to the rectum
It occurs 1-3 times per day
usually triggered by a meal with the gastrocolic response
how is the internal anal sphincter triggered to open
as the rectum fills, it stretches which activates the mechanoreceptors in the rectal wall and causes the sphincter to relax
How does the urge to defaecate reach the brain?
through afferents to the brain making it aware
how do we control the external anal sphincter
if it is acceptable to defaecate, the brain sends signals via the pudenal nerve to relax the skeletal muscle but if it is not then the muscle will be contracted
What helps stool come out of rectum
increasing the intra-abdominal pressure
difference between afferent and efferent
afferent is towards the CNS and efferent is away from the CNS
name some benefits of the flora in colon (4)
- increase intestinal immunity since can compete with pathogens
- promote motility
- make vitamin K2 and free fatty acids to be absorbed
- activate certain drugs
describe the differences between nausea, retching and emesis
nausea is just an unpleasant sensation in the throat or stomach but there are no muscular contraction. Retching involves rythmic reverse peristaltic contractions but there is no vomit and emesis is when gastric expulsions come out of the mouth
Process of vomiting
- Intestinal slow wave activity stops
- contraction from ileum to stomach (opposite of what it should be)
- glottis closes so no aspiration
- diaphragm and abdo muscles contract
- contents ejected
What is the largest endocrine organ of the body?
small intestine
what does the small intestine receive and secrete
receive: chyme, pancreatic juice, bile
secrete: intestinal juice
What is segmentation? How often does it happen and what controls it?
It is the alternating contraction of circular muscle in the small intestine which moves chyme back and forth
it occurs about 12 times per minute; it is more frequent in duodenum but net movement is slow to allow for absorption
initiated by pacemaker cells but the strength is controlled by the parasympathetic system (the more involved the stronger)
what is the gastroileal reflex
segmentation on an empty stomach that is triggered by gastrin
when does peristalsis in small intestine occur and what does it do?
peristalsis of the small intestine occurs during fasting times every 90-120 minutes and is a strong contraction that moves through the whole length of intestine to clear any debris and mucus
what is role of secretin
promotes secretion of pancreatic and biliary bicarbonate
What does CCK do?
Inhibits gastric emptying
activates secretion of pancreatic enzyme for digestions
relaxes sphincter of Oddi and contraction of gall bladder
enhances secretin action
What kind of receptors fo peptide hormones act on?
G-protein coupled receptors
Where is it released and what does it do GLP-1
released from L cells in ileum and stimulates insulin secretion, inhibits glucagon secretion, gastric acid secretion, and emptying
Where is GIP or gastric inhibitory peptide released from
K cells of duodenum and jejunum
List the secretions of the small intestine?
Gastrin secretin CCK GIP GLP-1 Motilin Ghrelin Succus entericus
What is the role of bicarbonate secreted by the pancreas?
Pancreatic duct cells secrete 1-2L of aqueous NaHCO3- per day. The bicarbonate is important in being able to neutralise acidic chyme so that the enzymes are at optimal PH and it protects the mucosa
What are the endocrine secretions of the pancreas
insulin, glucagon and somatostatin
What are the exocrine secretions of the pancreas?
digestive enzymes and NaHCO3- solution
Which cells release digestive enzymes and which ones release NaHCO3- solution
acinar cells and duct cells
What are the 5 main pancreatic enzymes?
trypsinogen, chymotrypsinogen, procarboxypeptidase A and B, Pancreatic amylase, Pancreatic Lipase
Why are the pancreatic enzymes stored in an inactive form?
To prevent self-digestion
enzymes are released in response to what being elevated
Ca2+
what are the three phases of gastric and pancreatic secretion?
cepahlic, gastric, intestinal
What is the intestinal pathway that leads to digestive enzyme secretion?
fat and protein in the duodenum leads to CCK release from I cells which is carried to the pancreatic acinar cells and activates secretion
How is secretion of bicarbonate activated in the intestinal phase?
acid in the duodenal lumen activates secretin release from S cells which is then carried to the pancreatic duct cells and results in bicarbonate secretion
What are the 4 main roles of the liver?
metabolism, activation and deactivation of hormones, storage, protection
what are the three types of metabolism
carbohydrate, fat, protein
what does carbohydrate metabolism in the liver involve?
gluconeogenesis (produce glucose from amino acids)
glycolysis (form pyruvate and then either lactate or acetyl-coA)
glycogenesis (store glucose as glycogen)
glycogenlysis (release glucose, as required)
What does fat metabolism in the liver involve?
synthesis of lipoproteins and cholesterol
ketogenesis
processing chylomicron remnants
what is cholesterol involved in?
needed to make bile acids and steroid hormones
what does protein metabolism in the liver involve?
synthesis of plasma proteins
converting ammonia to urea
transamination and deamination of amino acids
What are some proteins the liver synthesizes
coagulation factors
albumin
apolipoproteins
what does the liver store?
- fat soluble vitamins
- iron
- water soluble B12
- copper
- glycogen
what does protection of the liver function involve?
kupferr cells are liver phagocytes that destroy particulate matter like bacteria and old enterocytes like haemoglobin. They also produce immune factors
what substance does the liver detoxify?
bilirubin, drugs, ethanol
where is bile stored between meals?
gall bladder
What happens during a meal with bile?
during a meal the chyme in the duodenum stimulates CCK and vagal impulses to contract the gall bladder smooth muscle to release bile
The sphincter of Oddi opens so that bile can leave
What drains the primary juice into the biliary ductules and ducts
canaliculi
how are bile salts modified when before they are put into the duodenum?
Bicarbonate and water is added by the pancreatic ducts
What is bile juice made of?
primary biliary acids, water, electrolytes, lipids, phopholipids, cholesterol, IgA, bilirubin, metabolic wastes
Why could morphine worsen biliary colic pain?
Since it can cause sphincter of Oddi constriction and increase the intrabiliary pressure
Where are bile salts reabsorbed to go back to the liver?
at the ileum
What is added to secondary bile salts in the liver so that they can be reused?
glycine and taurine
What is the main function of drug metabolism in the liver
The liver converts parent drugs to less pharmacologically active, polar metabolites that are not absorbed by the kidneys so that they can then be excreted
What is an example of a drug that GAINS activity in the liver?
codeine turns into morphine
What happens during a phase 1 reaction?
drugs are made more polar by adding a chemically reactive group
what happens during phase 2 reactions in drug metabolism?
add an endogenous compound like glucoronic acid (glucoronidation) which usually results in an inactive product
what happens in hepatic failure that could cause encephalopathy
detoxification of ammonia fails and is then absorbed into the blood stream
Where is most water absobed?
small intestine
what are the main ways that water moves out of the lumen?
transcellular through aquaporins or paracellular through the gap junction in the epithelium
what are the main mechanisms of sodium absorption in the postprandial period and where does it occur
Na+/glucose co-transport or Na+/amino acid co-transport (both go into the cell) and occurs in the jejunum
What is the main mechanism for sodium absorption in the interdigestive period and where does it occur?
parallel Na+/H+ and Cl-/HCO3- and occurs in the ileum and colon ( Na and Cl move in and H and HCO3 move out)
what causes the Cl- to be absorbed in the small intestine
the sodium going into the cell from the Na+ glucose and amino acid transporters leaves a negative lumen so the Cl wants to leave
What is a method for sodium absorption in the distal colon?
epithelial sodium channels which are increased by aldosterone and are NOT regulated by cAMP like the other methods(which reduces NaCl absorption)
what causes Cl to be absorbed in the large intestine?
the negative lumen created by epithelial sodium channels
where does Cl- secretion occur
crypt cells
what is the role of CFTR
it is how Cl- exits the cell into the lumen if the concentration is too high
What activates CFTR
- bacterial endotoxins
- hormones and neurotransmitters
- immune cell products
- some laxatives
What are some causes of diarrhoea
- hypermotility
- reduction in NaCl absorption
- excessive secretion (increased cAMP and CFTR)
- poorly absorbed solutes in lumen
