Into where does the stomach empty chyme?
What happens to chyme in the duodenum?
It is conditioned
What features of chyme are modified in conditioning?
- Partly digested
How is the acidity of chyme modified in conditioning?
It is corrected by HCO3-
Where does the HCO3- used to correct the acidic nature of chyme in conditioning come from?
Secreted from the pancreas, liver, and duodenal mucosa
When is the HCO3- used to correct the acidity of chyme in conditioning produced?
During the production of gastric acid
How is hypertonicity of chyme modified in conditioning?
Corrected by the osmotic movement of water into the duodenum across its wall
How is the partly digested nature of chyme modified in conditioning?
Digestion is completed by enzymes
Where do the enzymes used to finish digestion of chyme in conditioning come from?
The pancreas and duodenal mucosa
Other than enzymes, what is required from the completion of digestion of chyme in conditioning?
Bile acids from the liver
What conditions does absorption require?
A large surface area, to which the luminal contents of the small intestine needs to be exposed to through gentle agitation for hours
How is the surface area of the small intestine maximised?
- Very long
- Increased by millions of villi projecting into the lumen
How do epithelial cells (enterocytes) arise?
By rapid division in the crypts between the villi, and migration towards the tips
What happens to enterocytes at the tips of the villi?
They are shed
What happens to newly formed enterocytes as they migrate to the tip?
What covers the luminal surface of the enterocytes?
What is the purpose of the microvilli present on the enterocytes?
- Further increase surface area
- Form the brush border
What does the brush border form?
An 'unstirred layer'
What happens at the unstirred layer?
Nutrients meet and react with enzymes secreted by the enterocytes, completing digestion prior to absorption
Label this diagram
- A - Muscle layers
- B - Villi
- C - Hepatic portal vein
- D - Lumen
- E - Capillary bed
- F - Lacteal
- G - Microvilli
- H - Villi
What is the function of the large intestines?
Absorb water from the indigestible residues of chyme
What do the large intestines do to the indigestible residues of chyme?
Convert them into semi-solid stool or faeces
What happens to the faeces formed by the large intestines?
It is stored temporarily and allowed to accumulate until defecation occurs
What are teniae coli?
The thickened bands of smooth muscle of the large intestines
What do the teniae coli constitute?
Most of the longitudinal coat of the large intestines
Where do the teniae coli run?
The length of the large intestine
What is the effect of the teniae coli on the part of the wall they are associated with?
They shorten it
Why do the teniae coli shorten the part of the wall they are associated with?
Because of their tonic contraction
What does the shortening of the wall due to teniae coli form?
What are haustra?
Where the colon becomes sacculated, or 'baggy', between the teniae
Label this diagram
- A - Right colic (hepatic) flexure
- B - Transverse colon
- C - Superior mesenteric artery
- D - Haustrum
- E - Ascending colon
- F - Ileum
- G - Ileocecal valve
- H - Cecum
- I - Vermiform appendix
- J - Rectum
- K - Anal canal
- L - External anal sphincter
- M - Sigmoid colon
- N - Tenia coli
- O - Cut edge of mesentery
- P - Descending colon
- Q - Epiploic appendages
- R - Transverse mesocolon
- S - Left colic (splenic) flexure
What are the sections of the small intestine?
What functions are common between all sections of the small intestine?
- Secrete protease and carbohydrase enzymes to complete digestion
- Secrete hormones
What hormones are secreted by all sections of the small intestine?
What are the functions of the duodenum?
- Addition of bile and pancreatic secretions
- Secretes HCO3- to neutralise chyme
- Osmotic movement of water into the duodenum, making chyme more hypotonic
Where in the duodenum are bile and pancreatic secretions added?
Ampulla of Vater
What is absorbed in the duodenum?
What are the functions of the jejunum?
- Uptake of things small enough to soak through the villi
What is absorbed in the jejenum?
- Amino acids
What substances are small enough to soak through the villi?
- Fatty acids
What is the function of the ileum?
What is absorbed by the ileum?
- Vitamin B12
- Anything not absorbed by the jejenum
Label this diagram
- A - Duodenum
- B - Ileocecal junction
- C - Cecum
- D - Appendix
- E - Duodenojejunal junction
How long does the large intestine take to finish the digestion of food?
About 16 hours
What are the functions of the large intestine?
- Sends indigestible matter to the rectum
What does the large intestine absorb?
- Any remaining absorbable nutrients
- Vitamins created by colonic bacteria
What vitamins are created by colonic bacteria?
- Vitamin K
What is the function of the rectum?
Stores and compacts faecal matter
In what form are carbohydrates ingested in the small intestime?
In the form of amyloses, amylopectins, or dissacharides such as sucrose
What is the structure of amylose?
Straight chain with α-1,4 bonds
What is the structure of amylopectin?
Branched, with α-1,6 bonds at branches
What do α-amylases act on?
Where are α-amylases secreted?
- In saliva
- By pancreas
What do α-amylases yield?
- Glucose and maltose from amyloses
α-limit dextrins from amylopectins
α-limit dextrins from amylopectins
What completes the breakdown of glucose?
Brush border enzymes
What enzymes are found in the brush border?
What does isomaltase do?
Breaks down branched molecules at α-1,6 bonds
What does maltase do?
Converts maltose to glucose
What does sucrase do?
Converts sucrose to glucose and fructose diamer
What does lactase do?
Converts lactose to glucose and galactose diamer
Where does the energy from the active absorption of glucose come from?
The Na+ gradient set up by Na/K/ATPase in the basolateral membrane
Where does glucose enter the epithelial cell?
Across its apical membrane
What transport is required to move glucose across the epithelial apical membrane?
Na+/Glucose Symporter, SGLT1
Other than glucose, what does SGLT1 transport?
Where does glucose leave the epithelial cell into the bloodstream?
Across the basolateral membrane
How does glucose leave the epithelial cell across the basolateral membrane?
Via facilitated diffusion through the GLUT2 transporter
How does fructose enter the epithelial cell from the lumen?
Via facilitated diffusion
What are proteins digested to?
What is an oligopeptide?
Short peptides, 10-20 AA's long
Where are proteins first digested?
In the stomach
What digests proteins in the stomach?
What secretes pepsin in the stomach?
What enzymes digest proteins in the duodenum?
What secretes the peptidases in the duodenum?
How do different peptidases vary?
They 'prefer' breaking different bonds
What peptidases are present in the duodenum?
What bonds does pepsin prefer to break?
Bonds near aromatic AA side chains
What bonds does trypsin prefer to break?
Bonds near basic AA side chains
What bonds does chymotrypsin prefer to break?
Bonds near aromatic AA side chains
What bonds does carboxypeptidase prefer to break?
C-terminal AA's with basic side chains
In what form can proteins be absorbed by the small intestine?
Both amino acids and small peptides (2/3 AA's)
How does absorption of proteins by the small intestine differ in neonates?
In neonates, the gut is 'open', so in addition to amino acids and small proteins, they are able to pick up whole proteins
What is the clinical importance of the 'open' gut in neonates?
It allows breast milk to confer passive immunity on babies via IgA absorption
What transporter is required for the active uptake of amino acids?
Na+/Amino acid co-transporters
How many types of Na+/Amino acid co-transporters are there?
At least 5
How do Na+/Amino acid transporters get the energy required for the active uptake of amino acids?
Using the Na+ gradient set up by Na/K/ATPase
Give 5 types of Na+/Amino acid co-transporters
Those that take up -
- Small, neutral AA's
- Neutral AA's, basic AA's, and cysteine
- Acidic AA's
- ß AA's (mainly taurine)
What facilitates some AA uptake?
How are dipeptides and tripeptides taken up?
By an active mechanism associated with pumping H+ into the lumen, which then returns by co-transport with the peptide
What is the result of fats being relatively insoluble in water?
They tend to aggregate into large globules
What is the result of fats tending to aggregate into large globules?
It prevents effective action of digestive enzymes
What excerbates the aggregation of fat into large globules?
Acid in the stomach
What happens to fats in the duodenum?
They are incorporated into micelles
What allows fats to be incorporated into micelles in the duodenum?
How big are the micelles formed by fats and bile acids in the duodenum?
Describe the structure of the fat micelles formed in the duodenum?
Fats in the middle and polar components of bile acids on the outside
What is the function of the fat micelles?
- Generate a high surface area for the action of lipases
- Carry products into the 'unstirred layer'
What is the effect of lipases on the fat micelles?
They cleave the fatty acids from glycerol
Where is the 'unstirred layer' located?
Immediately next to the mucosa
What happens to micelles in the unstirred layer?
Fatty acids can be released to slowly diffuse into the epithelial cells
What happens to the fatty acids from micelles once inside epithelial cells?
They are reconstituted into triacylglycerols and re-expelled as chylomicrons
What are chylomicrons?
Structured small particles
What are chylomicrons made up of?
Lipids covered in phospholipids
What do chylomicrons do?
Facilitate the transport of fat in the lymphatic system from the gut to systemic veins
How is sodium taken up by the small intestine?
Via diffusion into the cell, and actively transported across the basolateral membrane by Na-K-ATPase
What is the importance of sodium uptake by the small intestine?
It provides the driving force for the majority of absorption
What ion follows the movement of Na+?
What does the movement of Na+ and Cl-, coupled with all of absorption, give?
An osmotic gradient
What does the osmotic gradient in the small intestine do?
Leads to the uptake of water
What minerals are taken up by the small intestine?
How much calcium is absorbed from the small intestine each day, compared to how much is consumed?
700mg/day absorbed out of 6g consumed - >10%
How does Ca2+ enter the epithelial cell?
What allows Ca2+ to be taken up into the small intestinal epithelial cell by facilitated diffusion?
There is a low intracellular concentration
How is Ca2+ pumped out of the basolateral membrane?
What does both the facilitated diffusion of calcium and transport through the basolateral membrane require?
What is the uptake of calcium by the small intestine stimulated by?
Parathyroid hormone (PTH)
How much iron is consumed per day?
What constitutes most of the iron consumed?
In what form can iron be absorbed?
Only its ferrous form (Fe2+)
How is iron made into its ferrous form?
Gastric acid solubises iron complexes, making them ferrous
What happens to ferrous iron once it has been formed in the stomach?
Gastroferrin binds iron and keeps it ferrous
What secretes gastroferrin?
What secretes transferrin?
Intestinal mucosal cells
What does transferrin do?
Finds ferrous ions in the lumen
What happens once transferrin has found ferrous iron in the lumen?
The complex is taken into cells by endocytosis, spplit, and the iron is exported to the blood
What happens once the iron split from transferrin is exported to the blood?
It binds again to transferrin
How are water-soluble vitamins absorbed in the small intestine?
Via passive diffusion
What vitamins are water soluble?
- Vitamin C
- B vitamins
What is vitamin B12 absorbed with?
Where is vitamin B12 absorbed?
In the terminal ileum only
When does the intrinsic factor bind to vitamin B12?
In the stomach
What is the purpose of the intrinsic factor binding to vitamin B12?
To keep in soluble
What secretes the intrinsic factor that binds to vitamin B12?
The stomach mucosa
What occurs with vitamin B12 deficiency?
What causes pernicious anaemia?
Damage to the stomach, preventing it from secreting the intrinsic factor, or when the terminal ileum has been damaged or removed
When may the terminal ileum be damaged?
How is the uptake of Na+ related to the uptake of water?
It generates an osmotic gradient, which water follows
What does glucose uptake do?
- Stimulates Na+ uptake
- Generates its own osmotic gradient
What will stimulate maximum water uptake?
A mixture of glucose and NaCl
What is the mixture of glucose and NaCl known as?
Oral rehydration fluid
What must happen to the intestinal contents for effective absorption?
It must move very slowly (transit time in hours), whilst being gently agitated
How is the slow movement and agitation of intestinal contents achieved?
By a pattern of motility called segmenting
Are segmenting and perilstalsis the same thing?
No, they are very different
How is the small intestine divided?
What does each section of the small intestine have?
How does the frequency of the pacemaker change through the small intestine?
It gets less from the duodenum to the terminal ileum (12 times a minute to 8)
What is the decrease in pacemaker frequency phenomenom known as?
The intestinal gradient
What does each pacemaker drive?
A small section of intestine
What does the pacemaker driving of the section of small intestine cause?
Intermitted contraction of the smooth muscle along its length
What is the result of the intermittent smooth muscle contraction caused by the pacemaker?
It seperates the intestine into segments where the muscle is not contracted
What happens to the intestinal contents at each segment?
It is effectively mixed by movement from the portions that do contract
What happens after a few seconds of contraction of a segment?
The contractions relax, and the next pacemaker fires to make different areas contract
What is the purpose of segmenting?
Mixes the contents of the intestine
Segmenting itself does not proper contents
What does the intestinal gradient result in?
In terms of movement
There is a net movement, albeit slow, in a caudal direction
What is the large intestine naturally divided into?
Segments known as Haustra
How are Haustra formed?
The circular muscles are more complete than the longitudinal, which have been reduced to taenia coli
Describe the structure of taenia coli
- Thick circular muscle
- Thin longitudinal muscle
- Only 3 layers
What is the effect of contraction of hte smooth muscle in the walls of the Haustra?
It shuffles the contents back and forth
What happens as the intestinal contents is being shuffled back and forth by the Haustra?
There is slow absorption of the remaining water and salts, forming faeces
Where does the intestinal contents progress too from the Haustra?
The sigmoid colon
How is Haustral shuffling controlled?
Segmenting like control
What happens in mass movement of the colon?
Once or twice a day, there is a perilstaltic propelling pattern from the transverse through to the descending colon
What is the result of mass movement?
It forces faeces rapidly into the rectum
What happens when faeces is forced into the rectum?
It induces the urge to defecate
Why does faeces being forced into the rectum induce the urge to defecate?
Because the rectum is normally empty
What is mass movement often triggered by?
The gastro-colic reflex, triggered by eating
Does mass movement occur at certain times of the day?
Often does, because people 'like to be regular'
How many anal sphincters are there?
Two, internal and external
What kind of muscle is present in the internal anal sphincters?
What control is the internal anal sphincter under?
What happens to the internal anal sphincter when it recieves parasymphathetic stimulation?
What kind of muscle is present in the external anal sphincter?
Voluntary striated muscle
What control is the external anal sphincter under?
What happens once both anal sphincrers are relaxed?
Intra-abdominal pressure is increased, forcing expiration
What is the result of the increase in intra-abdominal pressure caused by the relaxation of the internal and external anal sphincters?
There is an expulsion of faeces
When is the voluntary control of the external sphincter overriden?
If rectal pressure becomes too high
What are the types of inflammatory bowel disease?
- Ulcerative colitis
- Crohn's disease
- Diversion Colitis
- Diverticular colitis
- Ischaemic colitis
What is ulcerative colitis?
An inflammatory disorder
Where does ulcerative colitis affect?
The rectum, and extends proximally in continuity to affect a variable extent of the colon
What is meant by UC extending in continuity?
There are no breaks in the inflammation
Where is there a high incidence of UC?
- US, UK and northen Europe
- Young adults
- More commonly in females
- More commonly in females
What is the mucosa of UC patients dominated by?
Th2 (T-helper) cells
What do Th2 cells produce?
- Transforming Growth Factor (TGF)
How does ulcerative colitis present?
- Rectal bleeding
- Abdominal pain
Where does extensive colitis affect?
Entire colon and rectum
What is extensive colitis also known as?
Pancolitis or total colitis
What is affected in distal colitis?
- Sigmod colon
- Descending colon
What is affected in proctitis?
What is Crohn's disease?
A condition of chronic inflammation
Where does Crohn's Disease affect?
Potentially any location of the GI tract from mouth to anus
When does CD have the highest incidence?
- 15-30 years
- 60 years
What is the mucosa of CD patients dominated by?
Th1 (T-helper) cells
What do Th1 cells produce?
- Interferon Gamma (IFN-γ)
What does the presentation of CD depend on?
The diseases location
What is the presentation of CD with upper GI involvement?
- Nausea and vomiting
- Small bowel obstruction
- Weight loss
- Loose stools
What is the presentation of CD when its a colonic disease?
- Passage of obvious blood
What may occur when there is termianal ileum involvement in CD?
Why may terminal ileum involvement in CD cause anaemia?
Because of poor absorption of vitamin B12
What causes inflammatory bowel disease?
- May have genetic predisposition
- Environmental factors
What genes may give genetic predisposition to inflammatory bowel disease?
By how much does having one copy of a risk allele increase the risk of Crohns?
By how much does having two copies of a risk allele increase the risk of Crohn's?
What environmental factors may increase the risk of inflammatory bowel disease?
- Early appendectomy
Why does NSAIDs increase the risk of IBD?
May be the altered intestinal barrier
What is an early appendectomy linked to?
Increased UC incidence
What is the effect of smoking on the risk of IBD?
- Protects against UC
- Increases risk of CD
What are the triggers for inflammatory bowel disease?
- Acute infections
How deep is the inflammation in UC?
How deep is the inflammation in CD?
What is the difference in the pattern of disease between UC and CD?
In UC it is continuous. In CD, it may skip area
What is the location of UC?
What is the location of CD?
Mouth to anus
Is there rectal involvement in UC?
Is there rectal involvement in CD?
Can be, but less common than in UC
What kind of ileal disease is sometimes present with UC?
What % of UC patients also have backwash ileitis?
Does Crohn's disease present with ileal disease?
Yes, it is common
Does UC cause fistulas?
Does CD cause fistulas?
Does UC cause perianal disease?
Does CD cause perianal disease?
Does UC cause granulomas?
Does CD cause granulomas?
Yes, in 50-60% of patients
Does UC cause overt bleeding?
It is unusual
Does CD cause overt bleeding?
It is less common
Does UC cause malnutrition?
It is unlikely
Does CD cause malnutrition?
It is more common
What cancer risk does UC confer?
What cancer risk does CD confer?
Colorectal cancer or small bowel cancer, depending on location
What will be seen on a radiograph in UC?
Collar button ulcers
What will be seen on a radiograph in CD?
String sign of Kantor
What methods are commonly used for investigating inflammatory bowel disease?
- Stool analysis
- Barium radiographs
- CT scan
- Capsule endoscopy
- Plain X-ray
How is a colonoscopy used to investigate IBD?
- Biopsies of involved mucosa
What will be looked for in stool analysis?
- Clostridium difficile toxin
How is a stool analysis conducted?
Using a culture
When will a plain X-ray be used to investigate IBD?
If bowel obstruction or perforation suspected
What is this image showing?
What macroscopic changes will be seen in CD?
- Involved bowel usually thickened, often narrowed
- Deep ulcers and fissures in mucosa may produce cobblestone apperance
- Fistulae and abscesses may be seen
What does the presence of fistulae and abscesses in CD reflect?
What macroscopic changes will be seen with UC?
- Mucosa looks reddened, inflamed and bleeds easily
- In severe disease, there is extensive ulceration with the adjacent mucosa appearing as inflammatory (pseudo) polyps
What microscopic changes will be seen with CD?
- Inflammation through all layers of the bowel (transmural)
- Increase in chronic inflammatory cells
- Lymphoid hyperplasia
Why can you see granulomas microscopically with CD?
What microscopic changes will be seen with UC?
- Superficial inflamamtion
- Chronic inflammatory cells infiltrate in the lamina propria
- Crypt abscesses
- Goblet cell depletion
How can differentation be made between UC and CD?
- Clinical data
- Radiological data
- Histological differences in rectal and colonic mucosa
How are samples of rectal and colonic mucosa obtained?
When may it not be possible to distinguish between UC and CD?
If the biopsies are obtained in the acute phase
What are patients considered to have when their disease cannot be distinguished between CD and UC?
Colitis of Undetermined Type and aEtiology (CUTE)
What may be of value when determining between CD and UC?
Serological testing for anti-neutrophil cytoplasmic antibodies (ANCA) in UC, and anti-Saccharomyces cervisiae antibodies (ASCA) in CD
What may be required to make an exact diagnosis sometimes?
Examination of a surgical colectomy specimen
When is a colonscopy performed with CD?
If colonic involvement is suspected
What will be seen on a colonscopy with CD?
Mild, patchy surface ulceration to cobblestoning
When is an upper GI endoscopy required with CD?
To exclude oesophageal and gastroduodenal disease in patients with relevant symptoms
When is small bowel imaging mandatory?
In patients with suspected Crohn's
How is small bowel imaging conducted?
- Barium follow through
- CT scan with oral contrast
- Small bowel ultrasound
What will be seen in small bowel imaging in a patient with CD?
- Asymmetrical alteration in the mucosal pattern with deep ulceration, and areas of narrowing or structuring
- String sign of Kantor
When is a perianal MRI or endoanal ultrasound used in patients with CD?
To evaluate perianal disease
When is a capsule endoscopy used in Crohn's disease patients?
When they have a normal radiological examination
What is the 'gold standard' investigation for the diagnosis of UC?
Colonscopy with biopsy
What is a colonscopy used for in UC?
To assess the disease activity and extent
Why is a plain abdominal X-ray used in UC?
To exclude colonic dilation
Why are other imaging techniques rarely used in UC?
As endoscopy is preferred
What is often seen on imaging with UC patients?
Collar Button Ulcers
What are Collar Button Ulcers?
Ulcer through the bowel mucosa to the muscle, then up and down in a 'T' shape
What treatment options are available for CD?
- Induction of remission
- Maintenance of remission
- Treatment of perianal disease
- Surgical management
How is remission induced in CD patients?
- Oral or IV glucocorticosteroids
- Enteral nutrition
- Anti-TNF antibodies
What is the name of the anti-TNF antibodies given in CD?
How is remission maintained in CD?
- Anti-TNF antibodies
How is perianal disease treated?
- Ciprofloxacin and Metrronidazole
- Anti-TNF antibodies
How do anti-TNF antibodies treat CD?
They bind to membrane bound TNF-α and induce immune cell apoptosis
When is surgical management required for CD?
- Failure of therapy with acute or chronic symptoms
- Failure to grow in children, despite children
What complications of CD may necessitate surgical management?
What surgical management may be performed in patients with CD?
- Ileorectal anastomosis
What is used to treat distal UC (proctitis)?
Topical or suppository corticosteroids
What is used to treat left sided UC?
Topical corticosteroid enema
What is used to treat extensive UC?
- Oral corticosteroids
When is surgical management required in patients with UC?
- Patients with complications
- Patients with corticosteroids dependence
What is the favoured surgical management in patients with acute UC?
Subtotal colectomy with end ileostomy and preservation of the rectum