Digestion Flashcards
What are the key layers of the gut tube
Mucosa
Submucosa
Muscularis externa
Serosa
Describe the muscosa
Innermost layer of gut tube
Consisting of epithelium, lamina propria and muscularis mucosae
What is the lamina propria
Loose connective tissue containing glands, lymph nodes and capillaries
What is the muscularis mucosae
A thin layer of smooth muscle which throws the muscosa into folds
Where is Meissner’s plexus found
In the submucosa hence it is also called the submucosal plexus
What does the submucosa contain (3)
Blood vessels
Nerves
Glands
What is the muscularis externa
Consists of 2 muscular layers : inner (circular muscle) and outer (longitudinal muscle)
The myenteric plexus is located between these layers
What is the serosa
What kind of epithelium does it have
The outermost layer of connective tissue
Covered by simple squamous epithelium
What is the name of the intestinal blood supplY
What does it also supply (supplies 5 structures in total)
The splanchnic circulation
Stomach, intestines, spleen, liver and pancreas
How much blood passes through the splanchnic bed
How much passes through the hepatic portal vein
1200ml per min
75% passes via the intestines to the liver in the HPV
How does oxygenated blood reach the liver
The hepatic artery
How does functional anaemia affect the gut
Splanchnic blood flow increases to 2500ml/min after a meal
What is the role of the parasympathetic NS in functional anaemia after a meal
Increases blood flow only locally (eg in salivary gland)
Elsewhere increased flow following parasympathetic stimulation may largely be a secondary effect, following increases metabolic rate which occurs with increased activity
Does the SNS have a big effect on splanchnic blood flow
Yes
Maximum sympathetic vasoconstriction can reduce blood flow to 300ml/min
Name 2 hormones that cause splanchnic vasoconstriction
Angiotensin II
ADH
What is the primary role of the gut’s great veins
As capacitance vessels, holding 20% of blood volume at rest
How much can venoconstriction affect the gut’s blood circulation
Venoconstriction can add ~400ml from the mesenteric veins and 200ml from the liver to the general circulation
What is the blood supply of a villus like
The arterial blood supply to each villus ascends from the base while the venous supply descends
This is called a counter current arrangement
How do water soluble substances leave the gut and enter the blood
Give 2 examples of water soluble substances
They enter the descending veins to ultimately enter the hepatic portal vein
Monosaccharides and amino acids
Where do the products of fat digestion enter the villi
They enter the lacteals
How are lacteals emptied
By irregular contraction of the smooth muscle in. The lamina propria, squeezing the products of fat digestion into the lymphatic system
What causes the smooth muscle to contact to empty the lacteals
An increase in interstitial fluid pressure
What prevents back flow in the submucosal lymphatics
Valves
What is the epithelium of the gut comprises of
A single layer of columnar cells
Why do gut epithelium have a v high turnover rate
They are vital for preventing microbial disease but are vulnerable to mechanical damage so must be constantly renewed
How often is the entire gut replaced
Every 2-6 days
Where do new gut epithelium come from
Stem cells from the crypts of Lieberkühn
What are the crypts of Leiberkühn
Blind ended tubules projecting into the gut lining between villi
If the epithelial cells are constantly renewed, what stops the barrier function of the gut being comprised
Before older cells are shed from the villus tip, a new tight junction is formed beneath them, between the neighbours
What is the ENS and what does it consist of
Enteric nervous system
Consists of the submucosal and myenteric plexuses which extend from the middle of the oesophagus to the colon
What do the submucosal and myenteric plexuses coordinate respectively
Submucosal: secretion
Myenteric: motility
Where is autonomic nervous system input particularly important in the gut
In the proximal gut and rectum
The intrinsic ENS and hormonal control is more important between these
Where do sympathetic fibres synapse
There is a cholinergic synapse in the prevertebral ganglia in the sympathetic chain OR in a separate pre-vertebral ganglion within the abdominal cavity (this second option is more common with fibres to the gut)
Post ganglionic fibres are typically cholinergic. True or false?
False
They are noradrenergic
What is usually the effect of the SNS on the gut
What is the exception
Inhibitory
It stimulates sphincter contraction
What is the PNS carried to the gut in
The vagus nerve
What kind of synapse is the PNS pre ganglionic fibres to the ENS
Cholinergic
What is the general effect PNS stimulation on the gut
What is the exception
Excitatory
Sphincter relaxation (inhibitory post ganglionic fibres release VIP)
Which nerves supply the distal colon, rectum and anus
From which region do they arise
Are they PNS or SNS
The pelvic nerves
sacral
Used to be thought they were PNS but actually SNS
What are IPANS
Intrinsic Primary Afferent Neurons
These are located entirely within the ENS
What do IPANs form
The afferent limbs of local reflexes eg response to peristalsis
Where are the cell bodies of general visceral afferent fibres to the gut
In the dorsal root ganglia or a homologous ganglion in the vagus
What are the 3 types of sensory fibres to the gut
IPANs
General visceral afferent fibres
Sensory fibres with cell bodies in the ENS (IFANs)
What do the general visceral afferent fibres do
What reflex are they involved in
Their axons transmit signals from the gut to the spinal cord or brainstem
Stomach reflexes, pain and defaecation reflexes
How many fibres in sympathetic nerves are afferent?
What about parasympathetic?
Sympathetic: 50%
Parasympathetic: 75%
What are vagovagal reflexes?
Reflexes in which both afferent and efferent arms are carried by the vagus nerve
Which nerves carry pain signals ?
Sympathetic
What are IFANs
Intestinofugal afferent neurons
Sensory fibres with cell bodies in the ENS, which send axons with sympathetic fibres to synapse at the pre vertebral sympathetic ganglia
What do IFAN fibres do
They form afferent limbs of long range inhibitory reflexes used to coordinate different parts of the gut
IFANs and pre vertebral ganglionic connections provide short cut around the multi synaptic pathway through the ENS
Why are feedback and feed forward mechanisms used in the gut
Feedback: to reduce mortality in proximal sections of the gut if it looks like contents are moving too quickly
Feed forward: to enhance motility in distal parts of the gut in order to make room
Give examples of 2 GI reflexes
Ileal brake
Gastrocolic reflex
What is the ileal brake
What communication is utilised
The effect of nutrients which have reached the ileum without being absorbed reducing motility and secretion in the more proximal parts of the digestive tract.
PYY and GLP-1
Nerve fibres
What is the gastrocolic reflex
Where food entering the stomach promotes motility in the colon
This may result in the need to defaecate
What chemical is involved in the signalling of the gastrocolic reflex
CCK
What kind of nutrient being present in the ileum is most likely to cause the ileal brake
Fat
Where is voluntary control exerted on the gut
Why is this possible
What else may affect bowel movements
Swallowing and defaecation
There is striated muscle here
Emotions, especially anxiety
What is neurocrine transmission
When nerve terminals release a transmitter to a target cell or into the blood
Name 4 neurocrine transmitters in the gut
ACh
Nitric Oxide
Vasoactive Intestinal Peptide
Noradrenaline
Discuss briefly ACh in the gut
Released onto muscarinic receptors
Excites gut smooth muscle and stimulates secretion
Discuss the effects of VIP and NO on the gut
Relax smooth muscle
VIP stimulates secretion
What is the effect of noradrenaline in the gut
Typically inhibitory but promotes sphincter contraction and vascular smooth muscle
What releases noradrenaline in the gut
Sympathetic neurons rather than neurons of the ENS
What is paracrine transmission
Locally produced substances diffusing through the ECF to work on neighbouring cells of a different type
How do endocrine transmitters travel
Via the blood
What kind of molecule are all gastrointestinal hormones
What secretes them
Peptides
Enteroendocrine cells
Where are enteroendocrine cells found
Scattered throughout gut endothelium
What secretes secretin
When does it happen
S cells
In response to acid secretion
Give the key roles of secretin
Stimulates pancreatic growth Stimulates bicarbonate and water secretion Inhibits gastric acid secretion Inhibits motility Promotes sphincter contraction
When was secretin discovered
What was the experiment
1902
HCl added to duodenum of a dog; pancreatic secretion increases
HCl added to denervated loop of jejunum (blood vessels intact) and pancreatic secretion increases
Extract of mucosa of jejunum into jugular vein: pancreatic secretion increases
What secretes gastrin
G cells in the gastric antrum and duodenum
What stimulates gastrin secretion
Nervous stimulation and the presence of peptides and amino acids
What are the roles of gastrin
Stimulate gastric acid secretion by parietal cells
Promote growth of oxyntic mucosa
What is CCK
Where is it secreted
Cholecystokinin
I cells in the duodenum and jejunum
What stimulates secretion of CCK
Long chain FFAs and monoglycerides
What is the role of CCK
Stimulates gall bladder contraction, pancreatic secretion and growth
Inhibits gastric emptying and appetite
Name the incretins
GIP (glucose dependant insulinotropic polypeptide)
GLP-1 (glucagon-like peptide 1)
What secretes GIP
What secretes GLP-1
K cells in the upper small intestine
L cells in both small and large intestine
When are incretins released
After a meal and augment insulin release from pancreas
How is knowledge of incretins used to combat type 2 diabetes
GLP-1 agonists are used to treat type 2 diabetes and are used to treat obesity
Discuss motilin
Secreted cyclically during fasting by M cells in the upper small intestine
Release is under neural control
Initiates the migrating myoelectrical complex
Which is the only GI hormone to stimulate appetite
Where and when is it secreted and where does it act
Ghrelin
Secreted by endocrine cells of the stomach in response to fasting
Acts on the hypothalamus
Also promotes growth hormone release from the pituitary
What is the Roux en Y surgery
A gastric bypass surgery where the lower small intestine is attached to the upper stomach
The duodenum is still attached in the bypass to allow bile secretion
What is potentiation
When the response of a cell with receptors for more than one type of chemical messenger, or different subtypes for the same messenger, to a combination of messages exceeds the sum of the responses to each individual message
How does the incretin effect act as potentiation
Plasma glucose alone stimulates insulin release
However if β cells are simultaneously exposed to the incretins, insulin production is greatly augmented
Why does glucose taken orally lead to higher insulin secretion than glucose injected intravenously
Oral glucose intake leads to incretin release
Give evidence of the potentiation in the incretin effect
Glucose taken orally leads to insulin secretion rates 2-3x higher than glucose injected intravenously because oral glucose leads to incretin release
How long can the smooth muscle in sphincters be tonically contracted
From minutes to hours
What kind of contraction is usually going on in the stomach and intestines
Phasic contractions
They contract slowly and rhythmically
Describe the electrical activity for phasic contraction in the smooth muscle of the stomach and intestine
A wave of depolarisation spreads through gap junctions and the cells are mechanically coupled, allowing coordinated contraction
What is single unit smooth muscle
Smooth muscle in which the cells are electrically coupled
How many nuclei in a smooth muscle cell
1
What are caveolae
Indentations in the plasma membrane of a smooth muscle cell
These increase surface area and act as calcium stores
What is the ratio of thin (actin) to thick (myosin) fibres in
a) smooth muscle
b) skeletal muscle
a) 10:1
b) 2:1
Describe the excitation contraction coupling in gut smooth muscle
Intracellular calcium binds to calmodulin
This complex activates myosin light chain kinase
This phosphorylates a light chain on myosin, allowing it to bind to actin
When calcium levels fall, myosin is dephosphorylated by myosin light chain phosphotase, which prevents further cycling
What is peristalsis
The general term referring to gut motility patterns which propel food in the anal direction
What is the peristaltic reflex
When stretching of the gut Wall elicits contraction of the longitudinal and circular muscle behind a bolus but relaxation of the muscle in front, propelling the food onwards
What is the propulsion of the peristaltic reflex know as
The law of the intestine
Which messengers mediate the peristaltic reflex
What about nervous stimulation
ACh mediates contraction
Nitric oxide mediates relaxation
But it is entirely mediated by the ENS
How may the bolus be detected in the gut
Maybe via mechanical stretch receptors in the myenteric plexus
Or
Mechanical/ chemical stimuli to the mucosa promoting serotonin release
What is 5-HT
Where is it released in the gut
Serotonin
Enterochromaffin cells
What modulates the smooth muscle of the muscularis external
Both stretch and chemo sensitive neurons indirectly, via the myenteric plexus
Can you get peristalsis in the striated parts of the gut
Yes it is controlled by somatic motor neurons
What special kind of peristalsis exists in parts of the gut like the colon
Reverse peristalsis/ retroperistalsis
What is the resting potential of the smooth muscle cells of the gut
Range from -70 to -40mV
Describe slow wave electrical activity
Slow waves of electrical activity are slow, undulating depolarisations of amplitude between 10 and 50mV
These slow waves represent the basal electrical rhythm intrinsic to the gut
They are responsible for phasic contractions
What happens to the smooth muscle between slow waves
It retains a basal level of tension referred to as tone
What is the range of the rate of slow wave occurrence
3-12 cycles per minute depending on the part of the gut
The shape of the wave also vary with location
What are ICCS
Interstitial cells of Cajal
The pacemakers of the gut: initiating and propagating slow waves
The ENS mainly innervates the ICCs rather than the smooth muscle directly
What is the structure of ICCs
Where are they
They are specialised smooth muscle cells containing few contractile elements
They are located mainly between the longitudinal and circular muscle layers
What is the pacemaker activity of ICCs based on
Calcium being take up/ released from intracellular stores, resulting in the activity of nearby plasma membrane channels
What do the fine processes of the ICCs form
Gap junctions with each other and nearby smooth muscle cells
What does depolarisation of smooth muscle by slow waves result in
When will contraction occur
The opening of L type voltage gated calcium channels in their membrane
If the amount of calcium entered exceeds the contraction threshold
When are action potentials generated in the gut
What are these called
If the calcium entered after slow wave depolarisation exceeds the electrical threshold
Spike potentials
How long are spike potentials
20msec
Longer than a sodium based AP
All smooth muscle requires APs to contract. True or false
False
What effect does ACh have on slow waves
What is the effect on contraction
Increases amplitude
Eg by opening action channels which contribute to depolarisation
More depolarisation results in more spikes, more calcium entry and a stronger contraction
What is the effect of NA on slow waves
What is the effect on contraction and why
Decrease amplitude by opening K channels for hyperpolarisation
Weaker contraction or no contraction as amplitude may be below threshold
Do sphincters depend on slow waves
No tonic contraction does not
It may be caused by a continuous sequence of APs, partial depolarisation of smooth muscle without APs or other mechanisms resulting in sustained levels of intracellular calcium
What is segmentation
Where different regions of circular muscle of the gut tube wall contract to aid mixing
What drives segmental contractions
Slow waves
But it is modulated by nerves and hormones (eg gastrin)
How does the PNS affect segmentation
PNS is excitatory, SNS is inhibitory
What is segmentation like without myenteric stimulation
Segmentation contractions become very weak in the absence of appropriate myenteric stimulation
What are the 3 major salivary glands
What do each produce
Submandibular - mucus serous mix
Sublingual - mucus/ serous mix
Parotid - serous
What are the major functions of saliva
Lubrication
Defence
Buffering
Digestion
How does saliva provide lubrication
Glycoproteins called mucins are produced by mucus secreting glands
What does salivary lubrication facilitate
The solution of food products facilitates taste, speech and swallowing
How does saliva provide defence
Lysozyme, lactoferrin and antibodies (IgA) are found in saliva
Proline rich proteins bind to and neutralise the effects of plant tannins
How does saliva act as a buffer
HCO3- ions raise the pH from slightly acidic (at basal severe thin levels) to ~pH 8 (during active secretion
How does saliva aid digestion
Contains salivary amylase you break down starch
What does amylase break starch down into
Oligosaccharides
Salivary amylase is inhibited by the low pH of the stomach. How can it continue to work despite this?
How long can it continue to work?
How much starch can it break down?
It is protected inside a bolus of food
For up to half an hour and has time to digest 75% of the starch in a meal
What is the primary secretion and what produces it
A fluid which is isotonic to plasma and high in NaCl
Produced by acinar cells
Why does primary secretion have high NaCl
The accumulation of NaCl in the acinar lumen draws water into the lumen by osmosis
Acinar cells only produce the primary secretion. True or false?
False
They also secrete salivary enzymes and other proteins via exocytosis
Some specialised acinar cells secrete mucus
How is saliva emptied from the lumen of the acinar cells to the ducts
Contraction of the myoepithelial cells
How do the duct cells modify the primary secretion
They make saliva more hypotonic
Which hormone acts on the salivary duct cells to promote ion exchange
What is this similar to
Aldosterone
Aldosterone acts here in the same way as in the kidney
What almost entirely controls salivation
The ANS
What phase of digestion involves the anticipatory response to food
The cephalic phase
How do the PNS and SNS act on salivation? (3 points each)
PNS: secrete ACh and VIP to promote vasodilation and increase blood supply, metabolism and growth.
Also contracts myoepithelial cells.
ACh opens more acinar cell channels increasing volume of saliva
SNS: promotes vasoconstriction but not during salivary reflex
Promotes myoepithelial contraction
NA acts on β1 receptors, increasing cAMP and thus increasing exocytosis, thereby increasing protein content
How does the PNS increase secretory volume
Releases ACh which acts on M1 and M3 receptors to increase [Ca2+] thus increasing channel activity
How is potentiation found in acinar cells
The cAMP (SNS) and Ca2+ pathways cross over within the acinar cells, potentiating the secretion of amylase
What is deglutition
Swallowing
What initiates the deglutition reflex
What coordinates this reflex
When a bolus of food is pushed to the back of the throat by the tongue, touch receptors in the pharynx start the reflex
The swallowing centre of the medulla and lower pons
How is the respiratory centre of the medulla affected by the swallowing centre?
What is this called
Respiratory centre is directly inhibited by the swallowing centre during the time it takes to swallow
Deglutition apnoea
Which muscles are involved in swallowing
What is the aim
It is v complicated involving the fine control of many striated muscles in the pharyngeal region
To swallow food without inhaling it
What does the upper oesophageal sphincter (UOS) consist of
Striated cricopharyngeus muscle
Describe the muscle of the upper third of the human oesophagus
Both longitudinal and circular layers are striated and innervated by the vagus
What is the muscle like in the middle third of the oesophagus
What about the last third
A mixture of smooth and striated
Entirely smooth
Where does a primary peristaltic wave begin
What does it do
Just below the UOS
Sweeps the bolus downwards at a rate of 3-5cm/sec
When is the secondary peristaltic wave initiated
What initiates it
What kind of reflex is it
If the bolus fails to move all the way to the stomach
Initiated by the persistent stretch of the oesophagus
Partly a local reflex, partly a vagovagal reflex
What is the lower oesophageal sphincter
What controls it
A region of specialised circular smooth muscle at the bottom of the oesophagus
ENS fibres which receive input from the ANS
Describe the action of the lower oesophageal sphincter
Normally tonically contracted
Sphincter relaxes even before food arrives as part of the feed forward Vagal reflex
What promotes the relaxation of the lower oesophageal sphincter as part of the Vagal feed forward reflex?
NO is the key ENS transmitter
Which structures are important in preventing acid entering the oesophagus
Lower oesophageal sphincter and surrounding crural diaphragm
Which reflex can lead to heart burn
What other condition can this lead to
The gastro oesophageal reflux
Barrett’s oesophagus
What is Barrett’s oesophagus
A condition of meta plastic change in mucosal cells in the lower oesophagus
The normal stratified squamous epithelium change to simple columnar epithelium with interspersed goblet cells that are normally only present in the intestines
When may the relaxation of the lower oesophageal sphincter be compromised
What can this lead to
Achalasia
Difficulty swallowing
What does the oesophagus secrete
What is used for
A small amount of mucus
Lubrication of food during swallowing and to protect mucosa against acid reflux
What is emesis
Where is it controlled
Vomiting
The vomiting centre in the medulla oblongata
What is stimulated to cause vomiting
A chemoreceptor trigger zone on the floor of the fourth ventricle of the brain
Why can the chemoreceptor trigger zone be triggered by blood borne drugs (emetics)
It lies outside the blood brain barrier
What are emetics and can they work within the gut
Drugs which induce vomiting
Yes they can send stimuli to the brain vie the vagus
Name an emetic
Ipecac
What does vomiting entail
Increased salivation
Retro peristalsis
Pressure changes
Relaxation of the lower oesophageal sphincter and eventually the upper oesophageal sphincter
Where does retro peristalsis begin in emesis
What must be relaxed to allow food to return to the stomach from the small intestine
From the middle of the small intestine and sweeps the contents up the digestion tract into the stomach
The pyloric sphincter
How does pressure change during emesis
What does this allow
Intrathoracic pressure decreases and abdominal pressure increases
Stomach contents to enter the oesophagus without retro peristalsis
Other than pressure changes, what is needed for the stomach contents to enter the oesophagus
Relaxation of the lower oesophageal sphincter
How are the pressure changes in emesis achieved
intrathoracic pressure is lowered by inspiring against a closed glottis
Abdominal pressure is increased by contracting abdominal muscles
Why does retching occur
After retching a few times what happens
If most of the mechanisms of emesis occur without the upper oesophageal sphincter relaxing
The sphincter relaxes and vomitus is expelled
When does bile enter the vomit
Due to duodenal contraction in severe vomiting
Name 3 animals that cannot vomit
Rats
Mice
Rabbits
Give 4 functions of the stomach
A good reservoir so good can be eaten quickly and released at a controlled rate
To facilitate digestion
To destroy ingested microbes through acidity
To regulate appetite through feed back effects to the brain and regulate late gut activity through feed forward mechanisms
How does oesophageal stretch affect the stomach
What does this allow
Which part of the stomach is not affected
What is this whole effect called
A vagovagal reflex causes the fundus and body of the stomach to relax
Up to 1500ml of food can be accommodated with little increase in pressure
The antrum
Receptive relaxation
How is the antrum different to the rest of the stomach
It has thicker muscular walls so can perform more powerful contractions than the proximal stomach
Discuss the plyoric sphincter
It is a functional sphincter but is not anatomically discrete
It is formed from the circular muscle of the plyorus
How open is the pyloric sphincter usually
What happens at the on set of feeding
Why is this
V narrow usually, limiting rate of stomach emptying
A small amount of liquid drains rapidly into the duodenum at the onset of feeding
The nutrients are sampled, which affects the rate of stomach emptying via a feedback mechanism
Where are ICCs found in the stomach
What do these do
In the body
Generate slow waves at a frequency of 3 per min
What happens to the slow wave generated by the ICCs in the stomach
Propagate down toward the pylorus and stop there
Why do stomach slow waves stop at the pylorus
Can APs propagate here
The pyloric sphincter lacks ICCs
Yes
What is the characteristic structure of gastric slow waves
How does this change towards the antrum
Spike and plateau
APs May be superimposed on the plateau
Which substances increase the duration and amplitude of the plateau in gastric slow waves in the fed state
Why do they do this
ACh and gastrin
To increase the chance of APs and contractions occurring
How do contractions spread through the stomach
What happens as the contractions approach the pyloric sphincter
They sweep down the body and antrum becoming increasingly powerful
The sphincter contracts to prevent passage of ingesta
Why does the pyloric sphincter close immediately following a meal
What is this process called
So the stomach contents are forced backwards towards the middle of the stomach
Retropulsion
Why does retropulsion occur in the stomach
To produce the “Antral mill” which breaks up larger particles and mix food with gastric secretion forming chyme
What happens to the pylorus between contractions
It relaxes and contents pass into the duodenum
What forces chyme through the pylorus
Tonic gastric pressure
What size do solids need to be to pass through the pylorus
<2mm in diameter
What did Hinder and Kelly show
When did they show this
The tougher and larger the food, the longer it stays in the stomach
1977
Describe the activity of the stomach in the fast state
Rests quietly for 90mins then 10 mins of intense activity
How do contractions in the stomach differ in the fasted state from the fed state
What does this mean
Contractions in the fasted state sweep food towards the pylorus rather than performing the antral mill
This helps larger particles to enter the duodenum
In the fasted state how does the wave of contractile activity move
What is this called
What initiates it
Continues down to the terminal ileum
This process is the migrating myoelectric complex
Motilin
What is the daily volume of secretion into the stomach lumen
2 litres
What are the 3 glands of the stomach mucosa
Cardiac
Oxyntic
Pyloric
What do the cardiac glands secrete and where are they located
Mucus
Near the entrance of the oesophagus
Where are the oxyntic glands
What do they contain
The oxyntic glands in the fundus and body contain parietal cells
Mucus secreting cells line
Chief cells also exist
What is another name for parietal cells in the oxyntic glands
What do they do
Oxyntic cells
Secrete HCl and intrinsic factor
What is another name for chief cells
What do they do
Peptic cells
Secrete pepsinogens and prochymosin
Where are the pyloric glands
What do they contain
In the antrum
Mucus secreting cells G cells (secrete gastrin)
Where is gastrin secreted into
The blood
What promotes pepsinogen secretion
Vagal ACh and a cholinergic response to acidity
How does acidity increase the amount of pepsins
Acidity catalyses the cleavage of inactive pepsinogens into pepsins
HCl also provides the low pH ideal for pepsin activity
What do pepsins do
Digest proteins and peptides
Cleave pepsinogens
How does acidity affect prochymosin
Acidity catalyses cleavage of prochymosin to form chymosin (AKA rennin)
What does chymosin do
Curdles milk in neonatal mammals, converting caseinogen (soluble) into casein (insoluble)
Why is caseinogen converted to casein in neonatal mammals
It allows milk proteins to remain in the stomach long enough to be acted upon by pepsins
How is milk curdled in human neonates
Pepsins curdle milk as the prochymosin gene is inactive in humans
Where is gastric lipase secreted
Stomach
What protects Vit B12 from stomach acidity
It binds to haptocorrin in saliva
What stops B12 being digested by proteases
Binds to intrinsic factor and this complex resists such digestion
What ultimately happens to B12
The B12-intrinsic factor complex is taken up into epithelial cells of the ileum by receptor mediates endocytosis
What is the only gastric function that is essential to human life
Secretion of intrinsic factor
Where is intrinsic factor secretes in dogs and cats
Pancreas
Give 4 functions of gastric acid
Delays gastric emptying
Solubilises and thus improves calcium and iron absorption, also helps to release B12 from food
Activates pepsinogens
Destroys many ingested microbes
What happens to the NaCl and HCl in gastric juice between meals
Juice contains more NaCl
HCl is secreted at a low basal rate
What happens within minutes of stimulation to parietal cells
Many tubules and vesicles, whose membranes contain transport proteins, fuse with the luminal membrane of the parietal cell
What happens to gastric juice wither the parietal cells are maximally stimulated
What happens to the intracellular pH
It becomes an isotonic solution of
HCl
Intracellular pH= 7
What is the pH of the parietal cell’s gastric gland during maximal secretion
What does this require of the pumps in the luminal membrane of the cells
0.8
They must pump against a million fold concentration gradient
What is the proton pump
The H+/K+ ATPase pumps
What generates the protons for the proton pumps on the luminal membranes of parietal cells
They’re generated from the intracellular reaction of CO2 with water (carbonic anhydrase is the catalyst)
This reaction forms H+ and HCO3-
How is HCO3- removed from parietal cells after it is generated as a byproduct of forming H+
Chloride shift
What kind of transporter is the chloride shift
Secondary active transporter
It’s energy comes from the electrochemical gradient for HCO3-
What is the alkaline tide
How is it detected
As acid secretion proceeds, CO2 is removed from the plasma and bicarbonate is added, making gastric venous blood more alkaline
A rise in urinary pH
3 things which act on parietal cells to increase acid secretion
Gastrin (endocrine)
Histamine (paracrine)
ACh (neurocrine)
How does gastrin reach the parietal cells
Travels in the blood from G cells in the antrum and duodenum
What prompts gastrin release
Local stretch reflexes (via ACh)
Vagal stimulation
Peptides, amino acids, and Ca2+ in the stomach lumen
Via which action does Vagal stimulation prompt gastrin secretion
Via gastrin releasing peptide (GRP)
What is gastrin‘a most important role
To prompt histamine production and release from ECL cells
What is the strongest agonist of HCl secretion
Histamine
Where is histamine released
From enterochromaffin - like cells (ECL cells)
What makes histamine a paracrine transmitter
It is secreted from ECL cells which are found in the gastric glands themselves to increase gastric acid secretion from parietal cells
What is the effect of ACh on acidity in the stomach
What else does it do, having a similar effect?
ACh is released from nerve terminals to promote acid release
Also increases release of histamine and gastrin
Inhibits release of somatostatin
What is the effect of ACh on somatostatin
Inhibits its release
How do ACh, gastrin and histamine increase acid secretion from parietal cells
ACh and gastrin increase free Ca2+
Histamine acts on H2 receptors to increase cAMP
Maximum acid secretion requires both Ca2+ and cAMP pathways to be activated, resulting in potentiation
3 things which mediate inhibition of acid secretion
Somatostatin (paracrine)
Secretin
Prostaglandins (paracrine)
How to remember 3 things which enhance gastric acid secretion
1 paracrine, 1 endocrine, 1 neurocrine
What secretes somatostatin
In response to?
What’s its effect
What kind of feedback is this
D cells
Luminal acidity
Inhibits parietal cells
Negative feedback- prevents excessive acid secretion
What releases secretin
In response to
S cells
Acid in duodenum
How does secretin inhibit acid secretion
Indirectly: stimulates Vagal afferent fibres, which reduce gastrin release fromm G cells
What do prostaglandins do
They are paracrines which promote bicarbonate and mucus production
What are the 3 phases of acid secretion
Cephalic
Gastric
Intestinal
What mediates the cephalic phase of acid secretion
How is the pH affected here? Why?
How much of total acid secretion does this account for
Feedforward ACh
No pH change as somatostatin release increases in response to increased acid secretion
30%
What stimulates gastric phase of acid secretion
What happens to the pH
What further happens in this phase (3)
Presence of food in the stomach
Initially protons are buffered by proteins in the food and luminal pH rises to 6. This rise releases secretory cells from inhibition
Stretch of stomach wall results in vagovagal and local reflexes which increase both gastrin and acid release
Peptides and amino acids stimulate G cells to further increase gastrin release
When does the intestinal phase of acid secretion occur
What happens initially
When chyme enters the duodenum
Duodenal Stretch triggers vagovagal reflexes, increasing acid secretion in the stomach and the products of protein digestion result in gastrin release from duodenal G cells
What happens in the intestinal phase of acid secretion after the initial reflexes
As duodenal contents become increasingly acidic, different vagovagal reflexes, local enteric reflexes, and secretin production all decrease acid secretion by the stomach
What protects the stomach mucosa
Where is this present
What is this lining called
What does it protect from
Secretion of mucus and HCO3- by the mucous cells forming the stomach’s epithelial lining and in the necks of gastric glands
Gastric mucosal barrier
Protection from mechanical and chemical damage
What pH is the luminal surface of the stomach
6-7
What replaces the epithelial mucous cells that are continually lost from the stomach surface
They are replaced by mucous cells from the necks of the gastric glands which migrate up and over the surface
What replaces the neck mucous cells if they replace epithelial mucous cells of the stomach
Stem cells which have divided and differentiated
What happens if the gastric mucosal barrier is compromised
Stomach’s surface can be attacked by acid and peptides, giving rise to a gastric ulcer
How are gastric ulcers treated
With drugs that decrease acid secretion, including H2 receptor antagonists and proton pump inhibitors
Name 2 H2 receptor antagonists and give an example of proton pump inhibitors
Ranitidine, cimetidine
PPIs eg omeprazole
What is are 2 predisposing factors to gastric ulcers
Overuse of NSAID drugs (eg aspirin)
Helicobacter pylori (a Gram negative bacterium that inflames the stomach Wall)
How are stomach ulcers, caused by helicobacter pylori, treated
Antibiotics as well as acid suppressors
What relaxes the pyloric sphincter
Inhibitory fibres in the ENS, which release NO
How do neural and hormonal reflexes slow stomach emptying
Inhibiting gastric motility
Tightening pyloric sphincter
What do enterogastric reflexes do
Slow gastric emptying when the distal gut is stretched
Name 3 things which appear in the duodenum, suggesting stomach emptying is too fast
Excess acid (if duodenal pH drops below 4)
Fat digestion products
Peptides and amino acids
What is absorbed by the stomach
Give 3 examples
Lipid soluble substances
Alcohol
Ketamine
Aspirin
The pancreas is purely exocrine. True or false?
False
It also produces endocrine secretion of insulin and glucagon
Describe the exocrine of the pancreas
Bicarbonate rich
Includes enzymes eg amylase, lipase, proteases, ribonuclease, deoxyribonuclease
Enters the duodenum
How do pancreatic acinar cells secret enzymes
How are proteases released
Exocytosis
As zymogens
What molecule helps protect acinar cells from inappropriate activation of trypsin
PSTI (pancreatic secretory trypsin inhibitor) is packaged in the same zymogen granules are trypsinogen
What secretes the bulk of pancreatic juice
In what form
Pancreatic duct cells in the form of bicarbonate rich solution
How do the PNS and SNS affect pancreatic secretion
PNS: stimulate
SNS: reduce, via vasoconstriction
How is each digestive phase controlled in relation to the pancreas
Cephalic: feed forward control
Gastric: vagovagal and local neural reflexes
Intestinal: pH <4.5 in duodenum and jejunum
Discuss the intestinal phase of digestion in relation to pancreatic secretion
Much high levels of secretion compared to other phases, mainly due to secretin
Secretin is a potent stimulator of bicarbonate and wager secretion from pancreatic duct cells
What is the main stimulus for CCK release in the duodenum
What does CCK do here
The presence of fat digestion products
Stimulates enzyme secretion from acinar cells and potentiates the effect of secretin (some effects may be indirect via vagovagal reflexes)
How do ACh, CCK, secretin, and VIP affect pancreatic cells
ACh and CCK: increase intracellular [Ca2+]
Secretin and VIP: increase cAMP
Potentiation is possible
What does cAMP do in both acinar and duct cells?
What channels is specifically affected?
Open luminal chloride channels, increasing secretion
CFTR
What is the CFTR
Cystic fibrosis transmembrane conductance regulator
What is the most common form of cystic fibrosis
Impaired electrolyte and water secretion into duct system
Clogged guts lead to severe maldigestion and nutrient deficiency
Pancreatic damage results from the blockage combined with premature activation of proteolytic enzymes
What secretes NaCl in the intestines
What is the mechanism of this secretion
Crypts of Lieberkühn
CFTR on apical membrane is enhanced by cAMP, increasing Cl- secretion
What causes cholera
What does cholera toxin result in
What does this ultimately lead to
The bacterium Vibrio cholerae
Results in permanently high [cAMP] leading to excessive Cl- secretion, with Na+ and water following.
Potentially life threatening diarrhoea
How long is the human small intestine in vivo
How long does it take chyme to pass through it
3-5m
2-5 hours
What controls small intestine motility
Slow wave activity
How does the rate of slow wave activity change from the duodenum to the ileum
12 per min in the duodenum
8 per min in the terminal ileum
What is required of the slow wave for contraction
The slow waves are large enough to generate action potentials
What is the most common form of motility in the small intestine
Describe the propulsion of this movement
Segmentation
Weakly propulsive
Peristalsis usually involves the entire small intestine at once. True or false?
False
Peristalsis usually involves only a short segment at a time
What increases peristaltic activity in the small intestine
Stretch of the gut wall
Where does the terminal ileum empty into and at what point
Into the large intestine at the junction of the caecum and colon - the ileocaecal valve
What is the ileocaecal valve
The projecting lips of the terminal ileum at the junction of the caecum and the colon
What reduces movement through the ileocaecal valve
What is the smooth muscle here called
High pressure in the colon and the colonoileal reflex
The ileocaecal sphincter
What happens at the junction of the small and large intestine when the terminal ileum is distended
A peristaltic reflex coordinated by the ENA pushes the contents through the ileocaecal valve
What is the gastroileal reflex
When a full stomach signals for ileal motility to be enhanced
What does the colonoileal reflex do
Inhibits movement through the ileocaecal sphincter when the colon is full
What are the nutrients absorbed everyday on an average diet
300g carbohydrate 100g fat 75g amino acids 75g ions 9L water
How is the surface area of the small intestine increased
What is the total increase
Folds of Kerckring: 3x increase
Villi: 10x increase
Microvilli: 20x increase
600x increase
What is the total surface area of the small intestine
250-400m^2
What forms the brush border in the small intestine
The microvilli in the epithelial cells
What do the crypts of Lieberkühn in the small intestine do
They are between villi and secrete fluid as well as containing stem cells for the replacement of desquamated epithelial cells
How often is the entire epithelium of the small intestine replaced
Every 3-6 days
How much fluid does the small intestine secrete everyday
How does the volume pancreatic and biliary secretions compare
Up to 2 litre
Small intestine secretion is matched in volume by pancreatic and biliary secretions
What does acid in the stomach do to protein
Helps denature it, rendering it vulnerable to attack
How much of protein digestion is contributed to by pepsins
What do they digest in particular
15%
Collagen
What primarily converts trypsinogen to trypsin
Where is this converter found
What else can do this conversion
Enteropeptidase
On the brush border of the upper small intestine
Trypsin itself can activate trypsinogen
What pancreatic proteases can trypsin activate
What do this molecules do
Trypsinogen
Chymotrypsin
Elastase
Carboxypeptidases
Digest proteins to peptides
How are peptides digested
By brush border peptidases
Where are brush border peptidases found
On the apical membranes of epithelial cells in the upper small intestine
How are the products of protein digestion taken up
Facilitated diffusion or secondary active transport into the cells
What happens to peptides once they are taken up by the small intestine cells
Peptides are further digested into amino acids which are then released from the cell by facilitated diffusion or secondary active transport
What happens to the protein digestion product glutamine after the protein is fully digested?
Glutamine is oxidised for energy within the rapidly dividing intestinal cells themselves
What is percentage of carbohydrates in the human diet is starch
50%
What does amylase do to starch
What does this produce
Cleaves the internal α-1,4 bonds but cannot cleave the α-1,6 branching links
Smaller chains of glucose: oligosaccharides (mostly 2 or 3 units long) and α-limit dextrins
What are α limit dextrins
Smaller chains of glucose, severed from starch, which contain the branch points that amylase cannot cleave
What do you call a chain of 2 glucose molecules
Maltose
Where is carbohydrate digestion completed
The brush border of the duodenum and jejunum
What breaks down α-1,4 bonds in oligosaccharides?
What about the α-1,6 bonds
Glucoamylase
α-dextrinase
What does lactase do
Digests lactose, forming glucose and galactose
What does sucrase do in the small intestine
Digests sucrose, forming glucose and fructose
What does trehalase do in digestion
Trehalose
How is galactose taken up in the small intestine
What else is absorbed here
Where is this found exactly
SGLT-1
Glucose
The apical membrane of the epithelial cells in the duodenum and jejunum villi
What is fructose taken up by in digestion
What can happen to it when it enters the cell
GLUT5
Some can be converted to glucose
How is fructose exported from the small intestine cells
Via GLUT2 on the basolateral membrane
Where is sodium absorption highest
Why here?
In the small intestine
The movement down its electrochemical gradient can be coupled to the movement of monosaccharides and amino acids
In which transporter is the movement of sodium down its electrochemical gradient is coupled to the movement of monosaccharides ?
SGLT-1
What are the 3 sodium transporters in the intestines
Na+/H+ antiporter
ENaC
SGLT1
Where is ENaC found in the gut
In the colon
Describe potassium digestion in the small intestine
K+ becomes concentrated as water is absorbed, providing a driving force for para cellular uptake by the small intestine
K+ movement in the colon is into the cells. True or false?
False
There is a net secretion of K+ from the colon via apical potassium channels
How is chloride absorbed in the gut
Where
Via para cellular pathways and by exchange with bicarbonate
Throughout the digestive tract
How does water enter the digestive tract
Through ingesta (2L/day) and gastrointestinal secretions (7L/day)
How does water enter the digestive tract through gastrointestinal secretions
From saliva, stomach, pancreas, bile and crypts
How much of the water that enters the digestive tract is absorbed where
7.5L by the small intestine
1400ml by the colon
What is the key place of water absorption in the small intestine
Ileum
How much of the water that enters the digestive tract is lost in faeces
100ml
What is reserve capacity
The gut’s ability to contain 2-3x the amount of water it usually does
What is the standing gradient model
Sodium is pumped into the intracellular clefts by the Na pumps, which are concentrated around the edges of the basolateral membrane.
Anions follow, creating a solute concentration gradient, which is highest near the tight junctions.
This concentration gradient decreases towards the open end where it becomes equal to the concentration in the bulk phase
The high concentration at the top draw water in from the cells and from the lumen via leaky tight junctions, putting pressure on the clefts.
The water and salts flow into the capillaries a
Why is absorption in the small intestine isosmotic
The small intestine epithelium is leaky
Why is there a larger osmotic gradient in the colon
The tight junctions between cells are tighter which limits back diffusion of ions
How is calcium and iron availability reduce in digestion
How is availability improved
They bind to other dietary constituents to yield insoluble salts
Gastric acid increases solubility while Vit C in the stomach helps reduce insoluble Fe 3+ to Fe2+
When is paracellular calcium uptake important
If calcium intake is high
Why may paracellular uptake of calcium not be important even if calcium uptake is high
If the active form of Vit D3 can up regulate the expression of proteins for trans cellular uptake (eg calbindin)
How is Fe3+ reduced in the duodenum
How is the Fe2+ produced taken up
Iron reductase on the duodenal brush border
Via the DMT1 or by haem
How does iron leave the duodenal cell
Ferroportin
How does iron travel in the blood (not in haem)
Bound it transferrin
What does hepicidin do to iron
Where is hepicidin produced
Reduces efflux of iron and excess iron is trapped in the cell, bound to ferritin
The liver
What happens to excess iron when it is trapped in the duodenal cell under the action of hepicidin
Binds to ferritin and is lost when the epithelial cell is shed
Why might we want to reduce iron availability
How do we do this
Bacteria need iron to grow so this mechanism is used to fight infection
Hepicidin production is increased in response to inflammation, reducing circulating iron levels
What are the fat soluble vitamins
A
D3
E
K
How are fat soluble vitamins absorbed
In a similar way to fat and transported mainly in lymph
How are water soluble vitamins taken up
Mostly in the small intestine via active transport or diffusion
How is B12 absorbed
How does it travel round the body
Bound to intrinsic factor it is absorbed via Receptor mediated endocytosis in the ileum
In the blood, bound to transcobalamin II
What is the liver divided into
Lobules
How big are lobules
Several mm long and 2 mm in diameter
Where are the portal triads
What are the portal triads composed of
Between hepatic lobules
A branch of the hepatic portal vein, a branch of the hepatic artery and a branch of the bile duct
What happens to mixed blood from the hepatic artery and portal vein
It drains through hepatic sinusoids towards the central vein, which empties into the hepatic vein
What like the hepatic sinusoids
Rows of hepatocytes
What are bile canaliculi
Tiny channels which drain bile produced by the hepatocytes towards the branches of the bile duct in the portal triads
How does blood flow in the liver’s lobules in relation to blood
Bile flows countercurrent to blood
Give 6 functions of the liver
- Metabolism (carbohydrate, protein, lipid)
- Bile formation
- Storage of vitamins and iron
- Destruction and detoxification of hormones, drugs and toxins
- Filtration of blood
- Blood reservoir
What kind of metabolism in the liver includes cholesterol synthesis and excretion in bile
Lipid metabolism
True or false: the liver only stores fat soluble vitamins
False
Also stores B12 (water soluble)
What does the first pass metabolism of toxins ensure
Ensures they do not reach the rest of the circulation
How does the liver help excrete fat soluble compounds
They are made more water soluble and are thus more readily excreted by the kidney by conjugation
Name a substance the liver might conjugate a fat soluble molecule with to make it more water soluble
Glucuronic acid
What is the key role of the lover’s filtration of the blood?
Removal of effete RBCs and any gut bacteria which have entered the hepatic portal vein
How can the liver supply blood to the circulation
The liver is a blood reservoir and venoconstriction can empty more blood into the circulation
How does the liver take up monosaccharides
What happens to them
Facilitated diffusion via GLUT2
They can be metabolised directly or inter converted
What can the liver converted glucose to for storage
Where is it stored? How much?
How long can this supply the body for?
Glycogen
Stored in liver (100g) and muscle cells (400g)
24 hours
Can all glycogen be exported?
No - the glucose from liver glycogen can be released into the blood but muscle cannot directly export glucose
What happens to excess glucose
It is converted to triglycerides by the liver, exported as lipoproteins and stored as fat in adipocytes
If carbohydrate stores are low, how can new glucose be made?
From lactate, amino acids (eg alanine and glycerol) vis gluconeogenesis in the liver
Can long chain fatty acids in triglycerides be made into glucose
What about propionate (a short chain fatty acid)
No
Yes - ruminants rely on this
How can intracellular proteins be decomposed
What then happens to them
Via lysosomal enzymes
Returned as amino acids to the blood
How are extracellular proteins digested
By macrophages
Most amino acids are recycled. What happens to the rest?
30-50g per day are broken down to provide energy
What does transamination allow
The liver to interconvert amino acids, pyruvate, and TCA cycle intermediates
Which amino acids must be synthesised and which must enter in our diet
Non essential - can be synthesised
Essential- must be included in the diet
What does it mean if an amino acid is conditionally essential
We may not be able to make them fast enough at certain times eg as we are growing as a child
What happens to excess amino acids
Either oxidised directly for energy or converted to glucose or ketone bodies
Urea and glutamine are produced and exported
What does bile contain and in what proportions
Bile acid: 65% dry mass of bile
Phospholipids: 20%
Cholesterol: 4%
Bile pigment: 0.3%
What are the 3 roles of bile
Promote fat absorption
Excrete waste
Protect
What products in bile promote fat absorption
Bile acids are surfactants and they are used with phospholipids
These normally conjugate with glycine or taurine to increase solubility and are found as salts of cations (bile salts)
How are primary bile acids made
What about secondary bile acids
From cholesterol in the liver
Primary acid salts can be converted to secondary bile acids by gut bacteria
How does bile aid excretion
Bile is the primary means of cholesterol excretion (directly or I the form of bile acids) when synthesis exceeds requirements
Excess heavy metals (including copper and cadmium) are also secreted in bile
3 things in bile that help it act as a protector
IgA
Mucus
Tocopherol
What is the role of the gall bladder
To collect and concentrate bile before expulsion in to the digestive tract during a meal
Where is the sphincter of Oddi
What happens to it between meals
At the entrance of the duodenum from the bile duct
It is contracted and bile is diverted to build in the gall bladder
What happens to the gall bladder during a meal
CCK promotes gall bladder contraction and relaxation of the sphincter of Oddi emptying bile into the duodenum
Where and how are bile acids taken up
How many are lost each day in faeces
In the terminal ileum by secondary active transport in the epithelium
Or
Absorbed passively by the colon
5% lost each day
How do bile acids return to the liver
HPV
Where can secondary bile acids be converted back into primary
What then happens to both primary and secondary bile acids
In the hepatocytes
Re-secreted into the bile canaliculi
The bile acid pool circles once during a meal. True or false?
False
Thanks to the enterohepatic circulation, the bile acid pool recirculates several times during a meal
Why is inhibition of bile acid uptake used to lower cholesterol levels
Bile acids are originally made from cholesterol so more is lost bile (and therefore more cholesterol) is excreted
What colour is bilirubin
Where is it made
Yellow
Spleen
Bone marrow
Liver
What happens to bilirubin when it is made
Travels in the blood, bound to albumin, and is taken up by the liver
What happens to bilirubin when it reaches the liver
It is rendered soluble by conjugation with glucuronic acid before excretion into bile
What happens to bilirubin in the bile
It is broken down to urobilinogen by bacteria in the ileum and colon
What happens to urobilinogen
Some is reabsorbed into blood and re-secreted in bile or secreted in urine
The rest is lost in faeces
What happens to urobilinogen in urine
It is oxidised slowly to urobilin when exposed to air
What colour is urobilin
Yellow
What happens to urobilinogen in the gut e
Some converted to urobilin
And some converted to stercobilin
What is the colour of stercobilin
Brown
True or false:
Bile salts are amphipatic
True
The hydrophobic domain binds to surface of a fat globule While hydrophilic domains face outward, stabilising the complex
What aids the detergent action of bile salts
Phospholipids and cholesterol
What does the detergent action of bile acids do to dietary triglycerides and lipids in the duodenum
Why do they do this
Emulsifies them into tiny emulsion droplets
Increase surface area for lipase attack
How big a lipid emulsion droplets
1μm in diameter
What is the helper protein of pancreatic lipase
Collapse
What do pancreatic lipase and colipase do
Hydrolyse triglycerides within an emulsion droplet to form 2 free fatty acids and one 2-monoglyceride
What do pancreatic enzymes other than pancreatic lipase do to the fatty acids from cholesterol esters and phospholipids
Remove them
What does the action of lipases eventually result in
What is usually mixed with this
Mixed micelles
More bile salts
What are mixed micelles
Tiny aggregates (5nm in diameter) of long chain fatty acids, monoglycerides, phospholipids and cholesterol
What do mixed micelles do
Ferry the products of fat digestion to the brush border, keeping the solution there saturated with lipid digestion products
What happened to the lipid digestion products at the brush border
They enter the epithelial cells either by diffusion or active transport
Where is dietary fat mostly absorbed
The end of the ileum
How does cholesterol enter the enterocytes
How can this absorption be reduced
Via special transporters
By plant sterols
How do plant sterols reduce cholesterol absorption
They displace cholesterol from mixed micelles but the sterols are then pumped out of enterocytes
Do fat soluble vitamins enter mixed micelles
Yes and then are absorbed by diffusion
How are fat digestion products and cholesterol delivered to the endoplasmic reticulum
What happens to them inside the ER
They bind to fatty acid binding proteins (FABP) within epithelial cells of the small intestine
Converted back to triglycerides
How are chylomicrons made
Triglycerides combined apolipoproteins, phospholipids and cholesterol
What type of particle is a chylomicron
A lipoprotein
Once the chylomicrons are created, where do they go?
To the Golgi apparatus and are released via exocytosis to enter the lacteals of the villi
How do the chylomicrons within the lymph enter the venous circulation
Via the thoracic duct
What catalyses the hydrolysis of the triglycerides within the chylomicrons
Where is it found
What happens to the FFAs produced
What happens to the rest of the chylomicron?
Lipoprotein lipase
Bound to capillary walls in tissues eg muscle, fat and lactating mammary glands
Transported across the endothelium and into cells where they can be resynthesised into triglycerides
Taken up by the liver
Where do most dietary triglycerides end up
What happens when blood sugar is low
In adipocytes
Some Triglycerides are hydrolysed and FFAs are released
What process allows FFAs to be used in most cells for energy
Which cells can they not be used for energy in
β-oxidation
The brain
What are LVDLs
When are they released
From where
Why
Very Low Density Lipoproteins
Secreted by the liver when fasting as a means of if exporting triglycerides and hepatic cholesterol to tissues
Like other lipoproteins and chylomicrons, What do VLDLs contain other than triglycerides and cholesterol?
Phospholipids and apolipoproteins
Name the ketoacids that are siphoned off from products of oxidation of lipids in the liver
What else can be produced
What are these 3 products known as
Acetoacetate
β-hydroxybutyrate
Acetone
Ketone bodies
How much of the brain’s energy can be derived from ketone bodies?
How long would it take for it to rach this percentage?
75% of its energy
Over the course of several weeks
If we have enough ketone bodies, the brain has no requirement for glucose. True or false?
False
Ketone bodies can only account for 75% of the brain’s energy
How might you recognise someone with ketosis?
Bad breath as the acetone is blown off from the lungs
How long is the large intestine
1.5m
How is the longitudinal muscle of the large intestine arranged
Into 3 bands (the taeniae coli) running through length of the colon up to the rectum
What are the non-permanent division in the large intestine calls
The haustra
How do the haustra arise
From the contractions of circular smooth muscle
What type of villi exist in the large intestine?
NONE
THERE ARE NO VILLI IN THE LARGE INTESTINE
How does the large intestine increase surface area?
It is internally folded
What is the key role of the proximal large intestine
Water and ion absorption
What does the transverse colon do
Stores faeces
3 key roles of the large intestine
To store, mix and process contents
To expose contents to microbes and absorb nutrients from microbial fermentation
To expel waste as faeces in a controlled manner
How are slow waves generated in the large intestine and at what rate?
ICCs within circular muscle generate slow waves at 3-6 per min
How can large intestine slow wave duration be extended
Why
ACh
ACh allows slow waves to elicit contractions of circular muscle in the absence action potentials
The longitudinal muscle of the large intestine requires action potentials to contraction. True or false?
True
What is transmit time usually through the stomach and small intestine
What about the large intestine
Under 12 hours
May be 1-2 days
The large intestine accounts for 90% of total transit time
Why is colonic transit time so long
What is the purpose
Colonic movements are low amplitude contractions which propel contents in a retrograde direction
To allow time for fluid absorption
What are the retrograde movements of the colon driven and modulated by?
Driven by slow waves
Modulated by autonomic input
How is the contents of the colon moved onward?
By High Amplitude Propagating Contractions (HAPCs) which occur periodically
What are HAPCs also called
Mass movements
What are HAPCs
How far do they move contents
What occurs to the haustra
Periodic waves of prolonged contractions
30cm
HAPCs are associated with the relaxation of te haustra
When do mass movements occur and which reflex is associated?
After a meal, promoted by the gastrocolic reflex
What is the internal anal sphincter
A thickening of the circular smooth muscle just inside the anus
How is the internal anal sphincter controlled
It has its own myogenic tone which is modulated by the ANS
What kind of muscle is the external anal sphincter
What controls it
Striated
Pudendal nerves
What is usual about the external anal sphincter muscle
Despite being skeletal muscle it is tonically contracted
What causes the resting tone of the external anal sphincter to rise
Any increase in intra-abdominal pressure other than when defaecating
True or false: the rectum is usually empty.
Yes but it can be filled by mass movement from the sigmoid colon
What happens when to rectum is filled with contents from the sigmoid colon? (5 steps)
Rectal sensory nerves signal to the sacral spine, which responds via the ANS in the pelvic nerves. This results in highly propulsive movements
The internal anal sphincter relaxes
The external anal sphincter may be voluntarily relaxed
Relaxation of pelvic floor muscles lowers the anus, straightening the rectal angle
Defaecation is aided by the Valsalva movement
What causes Hirschsprung’s disease?
It is a congenital disease whereby the ENS ganglion cells are absent in the descending colon And internal anal sphincter
What does Hirschsprung’s disease cause
What is the symptom called
Reflex relaxation of rectum and internal anal sphincter cannot occur as the rectum fills during mass movements.
This dilates the colon to a large size and may be perforated (congenital megacolon)
How much alkaline fluid and mucus is secreted each day
200ml
What does the consistency of stool reflect ?
The balance between overall GI secretion, tendency for the gut to hold water osmotically, and absorption
What may increases overall GI secretion be prompted by
Irritation
What can compact faeces be caused by
Why does this cause compact faeces
Decreases motility
It extends time for absorption
How what are the effects of stimulation of opioid receptors in the gut?
Name an exogenous drug that stimulates these receptors
When stimulated by endogenous transmitters, propulsion is decreased, secretion is decreased, and sphincter tone is increased
Loperamide
Name an endogenous transmitter that stimulates opioid receptors in the GI tract
β-endorphins
How much bacteria is there in the small and large intestine respectively
When is this mixture established
Small: 10^4 per gram of digesta
Large: 10^11-12 per gram of digesta
After birth gradually
Name 3 examples of colonic organism species
Bacteroides
Bifidobacterium
Eubacteria
Most colonic organisms are aerobic. True or false?
False
They are strictly anaerobic
How much of colonic organisms are escherichia coli
Are these aerobic
1%
No they are anaerobic
Name 3 organisms that are found in the gut that are not bacterium
Yeasts
Non pathogenic protozoa
Archaea
What do bacteria do to carbohydrates that reach the colon?
Metabolise it to produces volatile fatty acids
What do VFAs represent for colonic cells
An energy source
This is the colonic salvage of energy which would otherwise be lost
What vitamins do intestinal flora produce
K and B group
What is dietary fibre made of
Cellulose and other plant cell wall components that resist hydrolysis
4 things that a high fibre diet is good for
Provide a substrate for te metabolism of beneficial gut bacteria
Relieve constipation; prevent/ relieve haemorrhoids
Promote satiety
Protect against bowel cancer
How can the human digestive system break down cellulose
Therefore is cellulose digestion very important
Colonic bacteria are efficient at it
No cellulose digestion is of negligible importance
Where may VFAs account for up to 10% of caloric intake
In societies which eat poor quality, high fibre diets
How much urea passes through the colon
What happens to it here
About 20% of the urea synthesised everyday
It is metabolised by bacteria
Why do lactose intolerant people get gas and diarrhoea if they ingest lactose?
No lactase present so lactose is not digested
When it reaches the colon, bacteria thrive on it, producing metabolites which contribute to osmotic water retention, diarrhoea and excess gas
What is the test for lactose intolerance
What is the basis for this
The breath hydrogen test
The excess gas produced from bacteria who have metabolised lactose in the colon contains hydrogen. Some hydrogen enters the blood and eventually the alveoli to be exhaled
When might we lose gut bacteria
After diarrhoea or a course of antibiotics
What sprouts from the small caecum of humans
Vermiform appendix
What is in the mucosal walls of the appendix
What is the point of this
Gut associated lymphoid tissue (GALT)
Local defence against infection and might assist with maturation of B lymphocytes and production of of IgA antibodies
What might appendices be used for?
A store of beneficial microbes, used to re-inoculate the rest of the gut following diarrhoea
What are Helminths
Roundworms, flukes, and tapeworms
Where do Helminths live
In human intestines in 1/3 of the population especially poorer, warmer countries
What is flatus
What does it contribute to
Gas in the digestive tract
Borborygmi
What is the gas composition of flatus
N2=50% Small amount of swallow O2 H2=25% CO2=15% Methane=10%
Which gases In flatus come from colonic microbes
Methane
H2
CO2
What do archeon produce
Methane
How do methanobrevibacter smithii contribute to gases in flatus
They reduce CO2 to CH4 using H2
What decreases flatulence
But what else do they do
Sulphate reducing bacteria as they inhibit methane production
Produce hydrogen sulphide
What contributes to the odour of flatulence
Hydrogen sulphide Methyl sulphides Ammonia Indole Skatole Volatile amines VFAs
How much faeces are produced everyday
How much is water
120g
75%
What constitutes faeces
75% water 40% bacteria 15% fat 2.5% protein 15% inorganic matter And the rest is indigestible fibre
What colours faeces and gives it its smell?
Bile pigment - sterocobilin
Methyl sulphides
What causes Chagas’ disease
Where is this common
Trypanosoma cruzi
Rural Latin America
How many nephrons in the ENS
500 million
What part of the ANS to the ENS was considered to be parasympathetic but is not any more
Sacral outflow to the gut
Give examples of paracrine transmission(3)
Where are they produced and what is their action?
Histamine (from ECL cells within gastric glands to increase HCl secretion from gastric glands )
Somatostatin (released from D cells and inhibits parietal cells)
Prostaglandins (promote bicarbonate and mucus production )
Who discovered secretin
Ernest Starling
What is the etymology of cholecystokinin
Chole = bile
Cysto = sac
Kinin = move
(Greek)
Who discovered the ICCs
Santiago Ramón y Cajal
What is xerostomia
Dry mouth often caused by hypo function of the salivary glands
What does lysozyme do
Prevents bacterial infection by attacking the cell wall
What does lactoferrin do
Apart from its main biological function, namely binding and transport of iron ions, lactoferrin also has antibacterial, antiviral, antiparasitic, catalytic, anti-cancer, and anti-allergic functions and properties.
It reduces iron availability in the mouth to combat bacterial growth
Etymology of acinus
Latin for kernel
What is the purpose of the upper oesophageal sphincter
To prevent air entering the oesophagus when breathing
To prevent reflux of oesophageal contents into the pharynx, guarding airway aspiration
Why do we produce extra Saliva when vomiting
Vomit is highly acidic - saliva dilutes it and rinses the mouth
Saliva is also slightly alkaline so can help to raise the pH in the mouth
What is rennet used to do
Coagulate milk into curds and whey this helping in the cheese making process
What does a lack of intrinsic factor lead to
Pernicious anaemia and B12 deficiency
Where are H1 factors found
In the brain (eg hippocampus, thalamus, posterior hypothalamus)
What is Zollinger Ellison syndrome
A rare condition where tumours (gastrinomas) form in the pancreas or duodenum
These secrete large amounts of gastrin, increasing stomach acid secretion
Which hormones regulate gastric emptying
CCK GIP Glucagon GLP-1 PYY
What is the nick name for secretin
Nature’s antacid
What does the ileocaecal valve do
Controls passage of digested food from the small intestine into the large
What part of the gut is destroyed by coeliac disease
Small intestine
What class of drug disrupts hepatic cholesterol synthesis
Statins
What are Kupffer cells
Stellate macrophages in the liver
They remove senescent cells and particulates including bacteria
Where does gluconeogenesis occur
In the liver and the cortex of the kidneys
What is the main bile pigment
Bilirubin
What can bile obstruction lead to
Jaundice
Light brown urine
Bilirubin build up
What causes the makes on side of the bile salt hydrophilic
OH groups
Peptide bonds
Ionised acidic groups
What is the etymology of haustra
Latin for bucket
What is the etymology of taenia
Greek: “band”
Describe the Valsalva manoeuvre
A forceful attempted exhalation against a closed airway
What is the brand name of loperamide
When would you take it
Imodium
To decrease frequency of diarrhoea
Name 3 VFAs
Acetate
Propionate
Butyrate
How might you restore gut flora
Probiotics
Faecal transplant
What does vermiform mean
Resembling a worm
The duct cells reabsorb Na+ and secrete HCO3 - . Why?
HCO3- raises the pH of saliva
Reabsorption of Na+ allows regulation of volume as water follows salt
Where does aldosterone act in the gut
Aldosterone promotes ion exchange in the salivary ducts as in the kidney
Where would you find lipoprotein lipase
Capillary wall
Describe protein absorption
Partially broken down by peptin and gastric acid
Trypsin is activated by enteropepsidase
Pancreatic enzymes (trypsin, chymotrypsin, elastase and carboxypeptidase) break it down to peptides
Peptides are further digested by brush border peptidases and products are absorbed by cell
Most amino acids are released to blood, glutamine remains in the cell to be broken down for energy
