Unit 10; Crohns, coeliac, lactose intolerance and colitis Flashcards
What are some common causes of diahorrea?
Infections/food posioning
Antibiots - affect microbiome - risk of opportunistic pathogens
Medication side effect
Allergies (milk, fruits)
Stress and anxiety
Dietary factors
Travelers diarrhoea - acute, caused by infections typically E.coli and norovirus
What are the different classifications of chronic diahorrea?
Osmotic
Secretory
Inflammatory
Abnormal GI motility
How can diarrhoea be classified by time span?
Acute - less than 14days
Persistent: more than 14 days
Chronic: more than 4 weeks
What dietary foods increase the risk of diarrhoea?
Caffeine - activates Type 2 Bitter receptors in the oral cavity, increase gastrin and CCK, increases acid production and colon peristalsis
High insoluble fibre - wheat, nuts, beans and vegetables - osmotic diahorrea
What is diarrhoea?
A decrease in faecal consistency (increased fluidity), stools that cause urgency or abdominal discomfort or increase in frequency of stool (typically more than 3 times a day)
What is meant by osmotic diarrhoea?
Hypertonic fluid in the colon increases water secretion from the ECF by osmosis, down a water potential gradient
Due to malabsoprtion or osmotically active substances in the intestinal lumen, typically high salts such as MgSo4 used as a laxative
What is secretory diahorrea?
Copious secretion in the small intestine, the colon does not have the capacity yo reabsorb excessive water
Usually caused by infectious agents
What is gut motility diarrhoea?
Increased gut motility, water and electrolytes deliverd and passed to the colon too fast for water to be absorbed
Associted with parasitic infections such as Giardia
What is inflammatory diarrhoea?
Most commonly caused by IBD, less common include opportunistic infections such as TB.
More prevalent in patients who are immune compromised.
Fecal calprotectin is often used as a biomaker
What are the effects of stress on the GI?
1.Comfort eating - hedonic eating
2.Stress diarrhoea - increased motility of the colon
3.Cortisol can increase appetite, stimulate the lateral nucleus in the hypothalamus
4.Trophic effect of cortisol due to directed blood flow from the GIT - decreases GI motility, mucosa degenerates and enzyme production decreases (can lead to constipation)
5. Increases gastric acid and pepsin secretion
6. Altered microbiome - dysbiosis can increase the risk of inflammation and infection
What are the effects of diet on the GI system?
- Effect on microbiome: high plant fibres, low in fat and protein is beneficial, pro and prebiotics
- Diarrhoea and constipation risk: soluble v insoluble fibre, caffeine, high salt diet
- Alcohol - negative effect on the liver.
- Raw foods or undercooked foods - risk of food poisoning, bacterial infections
- Fizzy drinks, caffeine, alcohol - increase gastric acid secretion
What is the mechanism of action of loperamide?
Used for symptomatic treatment for acute diarrhoea, chronic dairrhoea and faecal incontinence - is available over the counter - is not recommended in children
Eneteric nuerons synthesise and release opioid peptides and neurotransmitters.
loperamide bind to mu-opiod receptor on circular and longitudinal muscle, and acts as agonist – this recruits G protein receptors kinases and activates downstream signalling that inhibits enteric nerve activity, particularly reduces Ach and prostaglandins.
Decrease peristalsis and fluid secretion in the GIT, increases transit time, increase rectal tone, increased tone of the anal sphincter, inhibits fluid and ion secretion
= leads to reduced daily decal volume and increased viscosity and bulk of feces, decreased urgency
Effects last from within 1 hour to 3 days
What treatments can be used as anti-diarrhoeal drugs?
1.Antibiotics - acute infection caused inflammatory diarrea - may use ciproflaxin
2.Opiods - codeine, loperamide hydrocholride
3. Muscarininc receptor antagonists -such as atropine
4. Oral rehydration therapy
What happens in order to initiate the defecation reflex?
Ingestion of food triggers to gastrocolic reflex - mediated by gut hormones and stretch receptors in the stomach - results in increased motility/peristalisis in the colon
Moves digestive content from the colon into the rectum
Distention is detected by stretch receptors in the colon
This triggers the defecation reflex
What are the different defecation reflexes?
Intrinsic reflex
Parasympathetic reflex/ extrinsic reflex
What happens during the intrinsic reflex of the defecation reflex?
Local enteric nervous system in the rectal wall
Myenteric plexus initiates peristalsis in the colon and rectum towards the anus
This reflex is often weak and needs to be fortified to cause a bowel movement
What happens during the parasympathetic defecation reflex?
Rectum stretch receptors activates nerve endings
This is relayed to the spinal cord then back out via parasympathetic fibres in the pelvci nerves
This intensifies peristalsis and relaxation of the internal anal sphincter
More effective in large bowel movements
What is the role of conscious control int eh defecation reflex?
Somatic nerve - the pudendal nerve - from the conscious cortex allows relaxation of the external anal sphincter, the puborectalis muscle and the pelvic floor
This allows defecation when it is socially convenient
What is lactose intolerance?
Arises due to lactase deficiency.
Lactase normally breaks lactose down into glucose and galactose.
When non-functional lactose builds up in the small intestine
Lactose is fermented by bacteria in the gut: this produces glucose, glactose, H2, Co2 and methane
Some gases are exhaled or absorbed, others remain in the tissue causing bloating
Lactose build up also increases osmolarity of the colon - lead to osmotic diarrhoea
How does the hydrogen breath test identify lactose intolerance?
1.Breath sample collected and tested for hydrogen
2. A solution of lactose (25g to 50g is given to drink
3. Breath samples are taken into a bag with a syringe attached and recorded at intervals to monitor for hydrogen production, normally take at least 10 samples
4. An increase by >220ppm over baseline indicates lactose malabsoprtion - and potential bacterial overgrowth
What is the ethnic link to lactose intolerance?
More common in Asian and south African ethnicities, particularly China
THought to be due to low dairy content in ancestoral diet (cow diseases or lack of cattle)
Western ethnicites evolved to maintain lactase after weaning in order to digest milk in diet (Lactase retainment)
Whilst in asian ethnicicities this was not needed so more likely to loose lactase during weening and not have a functional lactase as an adult causing lactose intolerance.
What is the meant by irritable bowel syndrome?
Functional disorder - change in the functioning of systems that than disease affecting the structure of the body
Diagnosis is based on ruling out other causative diseases
Does not involved inflammation or damage to the GIT - no detectable structural abnormalities
What is the potential pathology of IBS? Irritable bowel syndrome
Altered gut motility - increased intraluminal pressure, disorders peristalsis.
Visceral hypersensitivity to distention
Altered brain gut axis
Stress - exaccerabte only
Nreve endings in bowel are considered sensitive and nerves that control muscles are unusually active
What symptoms are normally associated with IBS?
Continuously or recurrently for 3 months: abdominal pain relieved by defaecation, change in stool frequency and consistently
Supporting symptoms include: mucorrhoea and abdominal bloating.
Why might an Irritable Bowel syndomre diagnosis be considered milder than an INflammatory Bowel disease?
IBS - does not increase risk of colon cancer, IBD does
IBS - typically require less hospitalisation and surgery is very rare.
What is the hereditary link to inflammatory Bowel disease?
NOD2 gene - loss of function
IL-23R gene - gain of function
TNFSF15 - gain of function, regulates immune homeostatise, resulting in increased INFy and NK responses
alpha4beta7 - increased function on inflammatory T cell phnoetypes
How is a NOD2 mutation linked to inflammatory bowel disease?
is an intracellular PPR found in epithelial cells in the gut , loss of function, unable to recognise bacteria, results in bacterial persitance and chronic inflammation
How is the IL23R gene linked to Inflammatory bowel disease?
Gain of function mutation
IL-23 released by macrophages, promotes development of Th17 - enhances neutrophil response.
Cascade signalling it increased inflammatory response such as TNFalpha release, and NK cell activation.
What is the pathophysiology of crohns disease?
1.Predisposition due to genetic and environmental factors
2.Onset thought to be triggered by dysbiosis of the gut microbiome
IMMUNE RESPONSE:
APC - presents antigen - activation of Th1 - cytokines release - activation of macrophages - increases platelet-activating factor, proteases and free radicals. Activation of IEL killing infected epithelial cells.
3.Impaired NOD2 ability leads to persistence of the pathogen, and reduced effectiveness of macrophages, paneth cells and dendritic cells. Leads to chronic inflammation
Impaired autophagy leading to failure to kill bacteria
4. Reduced barrier integrity allows pathogens to invade into the lamina propia and encourages further dysbiosis.
By this stage there is activation of the innate and adaptive immune response
5. Increase in pro-inflammatory cytokines in response to impaired bacterial clearance. Characteristics Th17 effector responses
6. Uncontrolled immune response damaging the bowel indicates IBD
What type of disease is crohns disease?
An inflammatory bowel disease characterised by an immune-mediated cause.
What are the key histological features of ulcerative colitis?
Inflammation in the mucosa (lamina propria) and submucosa
Ulceration of the mucosa
Mild fibrosis
What are the key histological features of Crohn’s disease?
Transmural inflammation
Granuloma
Fistula
Stricture
Fissuring Ulceration - skip lesions
Significant fibrosis
Why is there a tendency for gastric ulcers in the pylorus and cardia?
Contains majority of mucus glands
Damaged mucus glands - significantly decrease mucus production
Increased exposure of tissue that is less adapted to acidic environment to stomach acid resulting in ulceration
