Gastrointestinal Inflammation

Question 1

what is Gastroenteritis?

Answer 1

a very common condition that causes diarrhoea and vomiting

Question 2

what is Diarrhoea?

Answer 2

Loss of more than 500ml of fluid & solutes from GIT a day.
It is the most common symptom of acute GIT inflammation
It can be a life-threatening illness
Acute diarrhoea Lasts from 7 -28 days
Causes: viruses, stress, protozoa, intolerance to something, bacteria, drugs

Question 3

what do you use to see the different types of faeces?

Answer 3

the bristol stool chart

Question 4

what are the 4 types of diarrhoea?

Answer 4

Secretory Diarrhoea
Osmotic Diarrhoea
Hypermotility Diarrhoea
Defective Ion transport Diarrhoea

Question 5

2 mechanism of secretory diarrhoea?

Answer 5

Occurs when the secretions of the small intestine are so abundant that the capacity of the colon to reabsorb the excessive water is overwhelmed.
Mechanism 1:
Pathogenic bacteria colonise the small intestine and produce enterotoxins.
These toxins increase intracellular cyclic-AMP.
This inhibits neutral chloride-linked sodium absorption from the intestinal lumen by the villus cells.
In addition, it also directly stimulates chloride secretion by the crypt cells into the lumen.
The net result is a drive for water to move into the small intestinal lumen.
This then overwhelms the colon.
Mechanism 2:
Excessive activation of intrinsic neurons in pathological conditions may also cause secretory diarrhoea.
Some of these neurons release VIP that increases intracellular cyclic-AMP which then follows on from stages above.

Question 6

2 mechanisms of Osmotic Diarrhoea?

Answer 6

Mechanism 1
The presence of hypertonic fluid, poorly absorbed substances or osmotically active substances in the intestinal lumen can cause osmotic diarrhoea.
This is due to the movement of water from the extracellular fluid into the gut lumen.
Mechanism 2
Absorption disorders can also give rise to osmotic diarrhoea.
Absorption disorders can result in the presence of lactose or glucose in the intestinal lumen.
This can lead to secretion into the small intestine.
Furthermore, when these nutrients enter the large intestine, they may be fermented by colonic bacteria so that each molecule is degraded to a number of products, thereby increasing the osmolarity even further.
In both mechanism the volume of water transported into the lumen as a consequence may be too great for the colon to reabsorb it, and diarrhoea results.

Question 7

what is hyper motility diarrhoea?

Answer 7

the parasitic infection, giardia, is thought to increase motility in the intestines.
Hypermotility of the intestines can result in water and electrolytes being delivered to the colon at a rate too fast for the water to be absorbed in the colon.

Question 8

what is Defective Ion transport Diarrhoea?

Answer 8

The active transport of Na+ is a major determinant for the osmotic transport of water from the lumen into the blood
Therefore, the presence of inhibitors of Na+ transport will inhibit water transport into the blood causing diarrhoea.
Inhibitors of Na+ transport:
Bile acids (if not absorbed in the terminal ileum) can inhibit Na+ absorption in the colon.
Fat malabsorption will result in the fermentation of lipids in the colon to produce toxins that inhibit Na+ absorption.

Question 9

what is bacterial gastroenteritis + symptoms?
what are the 3 different types?

Answer 9

• when bacteria cause an infection in your gut
• can cause inflammation
• can’t absorb things means osmotic changes in the intestine
• Bacterial gastroenteritis is a digestive problem caused by bacteria.
  Symptoms include:
  Diarrhoea
  Bacterial toxin produced causes a shift in water and electrolyte excretion/adoption 🡪 Watery Diarrhoea
  Vomiting/nausea,
  Abdominal pain
  Haem-positive stool
  bloody stool.
  Fever
  Faecal evidence of inflammation

E- coli
C- diff
Salmonella

Question 10

what are the sources of Bacteria that cause Bacterial Gastroenteritis?

Answer 10

Bacterial Gastroenteritis resolves in a few days and treatment is not required

Question 11

what are the symptoms of gastroenteritis?

Answer 11

vary depending on what pathogen is the cause:

Question 12

explain the mechanism of E- coli

Answer 12

E coli
- different strains - given four letter abbreviations (EPEC, ETEC, EIEC)
- Pilli surrounding Ecoli allow it to adhere to epithelia, and produce toxins

• In the lumen, the E coli binds to the brush border of enterocytes and produce enterotoxin - become internalised
• toxins causes increased cyclic GMP –> inhibits intestinal fluid uptake
• also caused increase in cyclic AMP –> leads to hypersecretion of water and electrolytes –> net volume of GIT is higher than normal –> so fluid comes out as diarrhoea

Question 13

explain the mechanism of C.diff

Answer 13

• anaerobic bacteria
• readily transmissible - forms spores which is resistant to cleaning agents –> this why its easy to acquire in hospitals
• we all house it in our colon and it only becomes an issue when we are immune comprised or have a load of antibiotics
• this is bc antibiotics deplete microbes that help keep C.diff at bay –> this means C.diff can take over and grow –> increases inflammation and increases diarrohea

Question 14

explain the mechanism of Salmonella

Answer 14

acquired from undercooked food

Question 15

what is Acute inflammation of the GIT?
types?

Answer 15

Because the inflammation is acute the symptoms do not last very long.
Types of acute Inflammation of GIT:
Bacterial Gastroenteritis
Irritable bowel syndrome
Coeliac disease

Question 16

what is Irritable Bowel syndrome (IBS)?

Answer 16

The pathophysiology of IBS is broad and includes:
Exact cause in unknown
Brain-gut interaction
Psychosocial distress
Abnormalities involving motility
Visceral sensation
Recent studies have also shown altered gut immune activation, and intestinal and colonic microbiome are associated with IBS.
Symptoms usually occur between the ages of 20 – 40
Symptoms:

Question 17

symptoms and exacerbating factors of Irritable Bowel syndrome (IBS)?

Answer 17

Symptoms:
Diarrhoea
Pain
Bloating
Anxiety
Depression
Constipation
Exacerbating factors:
Patients also often associate food intake with IBS symptoms.
Foods such as wheat products, onions, fruits, vegetables, sorbitol, and some dairy can include short-chain, poorly absorbed, highly fermentable carbohydrates, which are known as FODMAPs.
FODMAPs have been associated with increased gastrointestinal symptoms in IBS patients.

Question 18

treatment of IBS?

Answer 18

Treatment:
IBS is a symptom-based disorder, and thus treatment goals are aimed at resolving symptoms such as the ones above.
Placebo Effect in IBS:
There is a strong placebo effect associated with IBS treatment.
Increasing evidence is suggesting a strong brain-gut association in IBS, which may account for the effectiveness of the placebo in the treatment of this syndrome.

Question 19

what is Coeliac Disease?

Answer 19

Coeliac Disease: An inappropriate autoimmune response to gluten that effects the SI
More specifically it results in a reaction to gliadin, a gluten protein found in wheat, barley and rye.
Upon exposure to gliadin, the enzyme tissue transglutaminase modifies the protein and immune system cross-reacts with the bowel tissue causing an inflammatory reaction
This Causes villous atrophy and crypt hyperplasia (gives flattened surface epithelium in place of villi)
This results in damage to the absorptive surface of intestine meaning you are unable to take nutrients from your food as effectively.

Question 20

diagnosis for coeliac disease?

Answer 20

Test for total immunoglobulin A (IgA), IgG and IgA tissue transglutaminase (tTG)
Follow this up with a small bowel biopsy

Question 21

what is the Site of Absorption of different molecules?

Answer 21

Knowing where the site of inflammation is throughout the GI tract can be helpful to understand why a patient might be poorly absorbing a specific type of nutrient.

Question 22

what is Chronic inflation of GIT?
two diseases its comprised of?

Answer 22

Inflammatory Bowel Disease is a chronic, immune related GIT condition.
IBD comprises of two diseases:
Ulcerative Colitis (UC)
Crohn’s disease (CD)

Question 23

what are symptoms of IBD?

Answer 23

Symptoms of IBD (consequences of intestinal inflammation)
Diarrhoea
Abdominal pain
Rectal bleeding

Question 24

causes of IBD?

Answer 24

Causes: (multifactorial)
Genetic predisposition
Immune system disturbance in GIT
Environmental triggers
The Immune system disturbance in the GIT is brought on by environmental triggers. However, this disturbance only happens to those with genetic predisposition to being susceptible to the environmental triggers.
The environmental triggers effect the composition of intestinal microbiome.
Examples of environmental triggers include:
Mode of birth: C section or natural birth
Geography
Diet: what you eat will determine what bacteria present in colon
Psychological state etc,
Socioeconomic factors
Infections
Smoking
The combination of multiple environmental triggers will act to turn on the intestinal immune response and cause IBD.
A trip to another country could be an ‘environmental trigger’ (change in diet/travelling stress)

Question 25

what would a Cellular Level Analysis of IBD show?

Answer 25

IBD – Cellular Level Analysis
Normal Individual:
In a normal individual there is a thick mucus layer on the epithelial barrier of the small intestine to protect the cells underneath.
There are also tight junctions between these cells (only allow water and small ions pass through not bacteria).
There are also immune sensing cells at the base of crypts which survey the contents of intestinal lumen (assessing good vs bad bacteria) to determine whether they need to secrete antimicrobial products and thus trigger an immune response.
In a normal person the equilibrium between t effector cells and t regulatory cells is in balance.

Question 26

what do environmental tiggers do to the intestines in IBD?

Answer 26

In IBD environmental tiggers (smoking, diet, medications) reduces the thickness of mucus layer and the tight junctions are no longer tight.
This means pathogenic bacteria can infiltrate the epithelia.
These bacteria that pass through are not associated with the normal microbiome normally (bad bacteria).
This bacterial infiltration will trigger an immune response.
This causes inflammation which causes symptoms of IBD.

Question 27

what is the diff between Chron’s Disease and Ulcerative Colitis’s?

Answer 27

Question 28

how to investigate for IBD?

Answer 28

Perform History
Examinations
Take bloods to measure white cells and inflammatory markers
Take a Stool sample:
Measure faecal calprotectin which comes from neutrophils in intestinal mucosa.
High FCP indicates IBD.
In IBD you get an immune response leading to the presence of lots of neutrophils in stool
Also in IBD the mucosa is leaky so neutrophils can invade into the lumen.
Biopsy - Histology
Imaging – colonoscopy:

Question 29

Treatment of UC and CD?

Answer 29

Medically, both UC and CD are treated the same:
Remission: Steroids
Maintenance:
Anti-inflammatory e.g. amino-salicylates
Immunosuppressants (Azathioprine)
Biologics (anti- TNFa)
Surgically, they are treated differently:
UC
Remove ulcerative colon:
Colectomy/hemicolectomy (+ileostomy)
Proctocolectomy (+ileo-anal pouch)
CD
Surgery is performed if there is obstruction of perforation
Segmental resection parts of SI and colon.
High risk of disease remaining in bowel (so surgery not too effective for CD)

New treatment: faecal microbial transplantation – where take faecal material from healthy individual and transplant it into patient and by doing so you transplant healthy microbial ecology which resolves the disease.