PBL 50 Flashcards
1
Q
Chronic inflammatory bowel disease is an umbrella term for which diseases?
A
- Crohn’s disease
2. UC
2
Q
What are the theories for IBD aetiology?
A
Probably a classical auto-immune disease with a genetic predisposition, and then sensitising & triggering elements but there are other theories:
- Toxic response to luminal contents: specific microbial pathogen, abnormal luminal constituents, or increased absorption of luminal macromolecules
- Enhanced immune response to normal constituents
- Autoimmune response: to epithelial cell or mucous glycoprotein, molecular mimicry or to immune cells.
3
Q
What are typical symptoms of IBD?
A
- Pain
- General malaise
- Fever
- Swelling
- Cramping
- Recurring or bloody diarrhoea
- Weight loss
- Extreme tiredness
- Stools w/blood, mucus & pus
4
Q
What are different complications of IBD?
A
- arthritis
- iritis
- erythema nodosum
- pyoderma gangrenosum
- sclerosing cholangitis
- aphthous stomatitis
- gall & renal stones
- colorectal cancer risk
5
Q
What are the different drugs used in treating IBD?
A
- Aminosalicylates (5-ASAs)
- Corticosteroids
- Immunosuppressants
- Biologics
6
Q
What are other treatments for IBD that modulate immune system and/or response to intestinal microbiota?
A
- Helminth therapy
- Fecal microbiota transplantation
- Bacterial cocktails
- Small-molecule approaches
7
Q
Give examples of 5-ASAs and how they treat IBD
A
- Sulphasalazine
- Mesalazine
- They dampen the inflammatory process
8
Q
Give examples of corticosteroids used to treat IBD and, in short, how they do this
A
- Prednisolone
- Prednisone
- Hydrocortisone
- Block substances that trigger inflammation
9
Q
Give examples of immunosuppressants used to treat IBD and, in short, how they do so
A
- Azathioprine
- Methotrexate
- Suppress the immune system
10
Q
Give examples of biologics used to treat IBD and, in short, how they do so
A
- Infliximab - anti-TNFa monoclonal antibody
2. Adalimumab - anti-TNFa monoclonal antibody
11
Q
Which mutations are associated with a genetic disposition to Crohn’s disease?
A
- NOD2
2. IL-23 receptor
12
Q
What is NOD2 and how does this mutation lead to Crohn’s?
A
- NOD2 is a pattern recognition receptor expressed in Paneth cells of the gut, so a mutation of NOD2 affects production of anti-microbial peptides.
- NOD2 is also expressed in innate immune cells, macrophages or DCs. So, once stimulated with a microbe, depending on the NOD2 phenotype, this may affect production by these innate immune cells of downstream cytokines, one of them being IL23
13
Q
How does mutation of IL-23R lead to Crohn’s?
A
IL-23 is produced by innate cells following the activation via PRRs. IL-23 acts on the IL23R which is expressed by innate cells such as the Th17 cell, so mutation in the IL23R will hinder the activity of innate cells
14
Q
What are risk factors for Crohn’s?
A
- FHx
- Smoking: increases the risk in genetic susceptible people and also risk of disease relapse & need for surgical resection
- Infectious gastroenteritis: risk increases 4fold
- Appendicectomy
- Drugs: NSAIDs increase the risk of relapse or exacerbation, but absolute risk is low.
- Microvascular infarction - Oral contraceptive pill (procoagulant)
- Triggers appears to be infective agents - Mycobacteria, measles virus
15
Q
Signs and symptoms of Crohn’s
A
- Persistent diarrhoea – including nocturnal diarrhoea with possible blood or mucus in stool
- Abdominal pain or discomfort
- Bleeding
- Weight loss
- Fistulae
- Perianal disease
- Faltering growth or delayed puberty
- Non-specific symptoms: fever, malaise, anorexia, fatigue.
16
Q
Crohn’s can affect any part of the intestinal tract, but which part is most commonly affected?
A
The small intestine
17
Q
Presentation of Crohn’s depends on the disease location, explain the difference in presentation depending on which part of the GI tract is affected: COLON, UPPER GI/SI, PERIANAL.
A
- Colon - bloody diarrhoea
- Upper GI/SI - Severe abdominal pain, vomiting, weight loss, small intestinal obstruction due to strictures
- Perianal - ulcers, fissures, perianal abscess, fistula
18
Q
What is the main principle for surgery of Crohn’s?
A
Preserve bowel length to avoid short bowel syndrome and intestinal failure
19
Q
Complications of Crohn’s?
A
- Malabsorption - Short loop/bowel syndrome due to repeated resection
- Fistula formation
- Anal lesions (60%) - Fissures, fistula
- Perforation, haemorrhage, toxic dilatation not as frequent as ulcerative colitis
- Increased risk of malignancy of small intestine but less frequent than ulcerative colitis
20
Q
How is Crohn’s diagnosed?
A
- On examination there may be abdominal tenderness or mass, for example in RLQ. Perianal pain or tenderness, anal or perianal skin tags, fissure, fistula, or abscess. Signs of malnutrition or malabsorption. Abnormalities of the joints, eyes, liver and skin.
- Routine bloods for anaemia, infection, thyroid, kidney and liver function
- CRP indicates inflammation and active disease
- Faecal calprotectin (released by the intestines when inflamed) is a useful screening test (> 90% sensitive and specific to IBD in adults)
- Endoscopy (OGD and colonoscopy) with biopsy is diagnostic
- Imaging with ultrasound, CT and MRI can be used to look for complications such as fistulas, abscesses and strictures.
21
Q
How is Crohn’s treated?
A
Inducing remission:
• First line: Steroids (e.g. oral prednisolone or IV hydrocortisone)
If steroids alone don’t work, consider adding immunosuppressant medication under specialist guidance: • Azathioprine • Mercaptopurine • Methotrexate • Infliximab • Adalimumab
Maintaining remission: • Tailored to individual patients based on risks, side effects, nature of the disease and patient’s wishes. It is reasonable not to take any medications whilst well. First line: • Azathioprine • Mercaptopurine
Alternatives:
• Methotrexate
• Infliximab
• Adalimumab
Surgery
• When the disease only affects the distal ileum it is possible to surgically resect this area and prevent further flares of the disease. Crohns typically involves the entire GI tract
• Surgery can also be used to treat strictures and fistulas secondary to Crohns disease.
22
Q
Explain the pathophysiology of UC
A
- Inappropriate immune response to an unknown environmental stimulus in the colon
- Unknown cause - Infection, diet, environmental factors, primary immunological defects, abnormalities in mucin, genetic disorders, psychomotor disorder
23
Q
Explain the progression of UC
A
- Always begins in rectum
- Can remain limited to rectum (ulcerative proctitis)
- Extends proximally to a variable length, or involve the entire large intestine (pancolitis) in a continuous manner
- Changes always most severe distally
- Primarily affects mucosa, but in severe disease, deeper layers can be involved - Fulminant colitis (toxic megacolon)
24
Q
Explain the risk factors for UC
A
- FHx: risk is greatest in first-degree relatives
- No appendectomy: appendicectomy before adulthood is thought to be protective against development of UC. Appendicectomy may be protective, delay onset, producing a milder form
- Not smoking: smoking appears to be preventive - Could be linked to increased glycoprotein synthesis maintaining protective mucosal barrier
- NSAIDs known to reactivate CIBD, especially UC, and in some patients, implicated in initiating UC
25
Signs and symptoms of UC
- Pr blood
- Frequency and urgency of defecation
- Cramping abdominal pain
- Fever
26
Diagnosis for UC
* Serum blood count: for anaemia, infection, thyroid, kidney and liver function
* CRP indicates inflammation and active disease
* Faecal calprotectin (released by the intestines when inflamed) is a useful screening test (> 90% sensitive and specific to IBD in adults)
* Endoscopy (OGD and colonoscopy) with biopsy is diagnostic
* Imaging with ultrasound, CT and MRI can be used to look for complications such as fistulas, abscesses and strictures.
27
Explain the treatment for UC
Inducing Remission
Mild to moderate disease:
• First line: aminosalicylate (e.g. mesalazine oral or rectal)
• Second line: corticosteroids (e.g. prednisolone)
Severe disease:
• First line: IV corticosteroids (e.g. hydrocortisone)
• Second line: IV ciclosporin
Maintaining Remission
• Aminosalicylate (e.g. mesalazine oral or rectal)
• Azathioprine
• Mercaptopurine
Surgery
• Ulcerative colitis typically only affects the colon and rectum. Therefore, removing the colon and rectum (panproctocolectomy) will remove the disease. The patient is then left with either a permanent ileostomy or something called an ileo-anal anastomosis (J-pouch). This is where the ileum is folded back in itself and fashioned into a larger pouch that functions a bit like a rectum. This “J-pouch” which is then attached to the anus and collects stools prior to the person passing the motion.
28
Crohn's vs UC: NESTTS vs CLOSEUP
Crohn's - think crow's nests
N - No blood or mucus (less common)
E – Entire GI tract
S – “Skip lesions” on endoscopy
T – Terminal ileum most affected and Transmural (full thickness) inflammation
S – Smoking is a risk factor (don’t set the nest on fire)
Crohn’s is also associated with weight loss, strictures and fistulas.
```
Ulcerative Colitis (remember U – C – CLOSEUP)
C – Continuous inflammation
L – Limited to colon and rectum
O – Only superficial mucosa affected
S – Smoking is protective
E – Excrete blood and mucus
U – Use aminosalicylates
P – Primary Sclerosing Cholangitis
```
29
Are granulomas more commonly found in UC or Crohn's?
Crohns
30
UC vs Crohn's rectal involvement?
50% of cases of Crohns have rectal involvement but 100% of UC
31
Is the intestinal wall thickened in UC or Crohn's?
Crohn's
32
Which layers are affected in UC vs Crohn's?
```
UC = Superficial
Crohn's = ALL layers
```
33
Causes of malabsorption?
- Cystic fibrosis
- Chronic pancreatitis
- Lactose intolerance
- Coeliac disease
- Whipple disease
- Parasites: Giardia lamblia, Strongyloides stercoralis, Necator americanus (hookworm)
34
Signs and symptoms of malabsorption
- Chronic diarrhoea
- Bloating and gas
- Avoiding specific food
- Growth failure
- Steatorrhea
35
Which nutrient is malabsorbed in hypochromic, microcytic anaemia?
Iron
36
Which nutrient is malabsorbed in macrocytic anaemia?
B12, folate
37
Which nutrient is malabsorbed in bleeding, bruising, petechiae?
Vitamins K and C
38
Which nutrient is malabsorbed in carpopedal spasm?
Calcium, magnesium
39
Which nutrient is malabsorbed in oedema?
Protein
40
Which nutrient is malabsorbed in glossitis?
Vitamins, B1, 2, 3, 6 and 12
Folate
Niacin
Iron
41
Which nutrient is malabsorbed in night blindness?
Vitamin A
42
Which nutrient is malabsorbed in pain in limbs/bones/pathologic fractures?
Calcium
Potassium
Vitamin D
Magnesium
43
Which nutrient is malabsorbed in peripheral neuropathy?
Vitamins B1, 6 and 12
44
Risk factors for malabsorption
- Problems with the liver or pancreas
- Difficulty moving food in the intestines
- Crohn’s disease, coeliac disease, parasite infection, or other intestinal disease
- Laxative use
- Antibiotic use
- Intestinal surgery
- Alcohol use disorder
45
Diagnosis for malabsorption
Blood tests - FBC
Stool tests - for Xs fat in stool
Breath tests - hydrogen gas in intolerances
Imaging tests - to check function/structure of digestive organs
46
Treatment for malabsorption
Dependent on specific disease causing the malabsorption
47
What is coeliac disease?
A condition where the immune system attacks the body’s tissues when gluten is consumed, damaging your small intestine so it is unable to absorb nutrients
48
Explain the pathophysiology of coeliac disease
- Genetics - HLA-DQ2 heterodimer allele (& HLA-DQ8)
- Gliadin (a glycoprotein extract from gluten) is thought to be toxic to the individual’s enterocytes, through the overexpression of IL-15 in the intestine - ultimately resulting in epithelial cell damage & increased intraepithelial T cell lymphocytes
- Gluten-sensitive T cells are activated when gluten-derived peptide epitopes are presented, the inflammatory response causes characteristic mucosal villous atrophy in the small bowel
49
Signs and symptoms of coeliac disease (when eating gluten vs general symptoms)
When gluten is consumed:
- Diarrhoea (with a particularly bad smell)
- Stomach aches
- Bloating & flatulence
- Indigestion
- Constipation
More general symptoms:
- Fatigue (as a result of malnutrition)
- Unintentional weight loss
- Itchy rash (dermatitis herpetiformis)
- Infertility
- Nerve damage (peripheral neuropathy)
- Disorders affecting coordination , balance and speech (ataxia)
50
Risk factors for coeliac disease
- Family history of coeliac disease/ dermatitis herpetiformis
- Type 1 diabetes
- Down syndrome or turner syndrome
- Autoimmune thyroid disease
- Microscopic colitis (lymphocytic or collagenous colitis)
- Addison’s disease
- severe/ persistent mouth ulcers
51
Diagnosis for coeliac disease
- Blood tests - testing for antibodies of coeliac disease
| - Biopsy - an endoscope is inserted into the mouth and passed down to the small intestine
52
Management for coeliac disease
- Gluten-free diet
- Can cause the spleen to work less, therefore extra vaccinations may be needed, including:
1. Flu jab
2. Hib/ MenC vaccine
3. Pneumococcal vaccine
- Supplements
53
Explain the physiology of bowel movements
- Waste material is stored as faeces to be removed in the rectum
- As the rectum is filled, the walls expand and stretch receptors stimulate desire to defecate
- The urge arises from contraction of rectal muscles, relaxation of the internal anal sphincter and an initial contraction of the external anal sphincter
- Internal anal sphincter is controlled by parasympathetic fibres, that relax involuntarily
- External anal sphincter is skeletal muscle controlled by somatic nerve supply from the inferior anal branch of the pudendal nerve – allowing for conscious control of defecation
- Rectum distension initiates the rectosphincteric reflex, relaxing the internal sphincter
- A series of reflexes leads to:
1. Relaxation of external sphincter
2. Contraction of abdominal wall muscles
3. Relaxation of pelvic wall muscles
4. Peristaltic waves then facilitate movement of faeces through the anal canal
54
What is the definition of inanition?
Exhaustion caused by lack of nourishment
55
What is the definition of anorexia?
Lack/loss of appetite for food
56
What is the definition of cachexia?
Weakness and wasting of the body due to severe chronic illness
57
What is the definition of steatorrhoea?
Increase in fat excretion in stool
| - One of the clinical features of fat malabsorption
58
Steatorrhoea is noted in many conditions such as...
- Pancreatic insufficiency
- Coeliac disease
- Tropical sprue
59
Mechanism of loperamide
- Slowing intestinal motility & affecting water and electrolyte movement through the bowel
- Inhibits peristaltic activity by a direct effect on the circular & longitudinal muscles of the intestinal wall (inhibits the release of acetylcholine and prostaglandins)
- Non-selective calcium channel blocker and binds to opioid mu-receptors
60
Indications for loperamide
- Acute diarrhoea
- Chronic diarrhoea
- Faecal incontinence
- Pain of bowel colic (in palliative care)
61
Contra-indications of loperamide
- Active ulcerative colitis
| - Antibiotic-associated colitis
62
Side effects of loperamide
1. Common/ very common
- Gastrointestinal disorders
- Headache
- Nausea
2. Uncommon
- Dizziness
- Drowsiness
- Dry mouth
- Gastrointestinal discomfort
- Skin reactions
- Vomiting
63
Mechanism of antispasmodics
Work by inhibiting acetylcholine in the brain and at the nerves, preventing impulses from the parasympathetic nervous system from reaching smooth muscle and causing contractions.
64
Indications for antispasmodics
- Diarrhoea
- Gastrointestinal cramps
- Overactive bladder
- Muscle spasms
- Breathing problems
- Movement disorders
65
Side effects of antispasmodics
- Dizziness
- Drowsiness
- Weakness
- Blurred vision
- Dry eyes/mouth
- Nausea
- Constipation
- Abdominal bloating
66
Notifiable disease list
```
Acute encephalitis
Acute infectious hepatitis
Acute meningitis
Acute poliomyelitis
Anthrax
Botulism
Brucellosis
Cholera
COVID-19
Diphtheria
Enteric fever (typhoid or paratyphoid fever)
Food poisoning
Haemolytic uraemic syndrome (HUS)
Infectious bloody diarrhoea
Invasive group A streptococcal disease
Legionnaires’ disease
Leprosy
Malaria
Measles
Meningococcal septicaemia
Mumps
Plague
Rabies
Rubella
Severe Acute Respiratory Syndrome (SARS)
Scarlet fever
Smallpox
Tetanus
Tuberculosis
Typhus
Viral haemorrhagic fever (VHF)
Whooping cough
Yellow fever
```
67
Microbiology of gastroenteritis: viruses
norovirus (most common in adults)
adenovirus
astrovirus
rotavirus (most common in children)
68
Microbiology of gastroenteritis (bacterial)
```
E. coli
campylobacter jejuni
salmonella
shigella
C.diff (hospital)
Listeria
Diphtheria
```
69
Microbiology of gastroenteritis: parasitic
Giardia lamblia
entamoeba histolytica
cryptosporidium spp.
70
Pathophysiology of gastroenteritis
- Viruses infect enterocytes in the villus epithelium of the small intestine, resulting in the ‘leaking’ of fluid and electrolytes into the intestinal lumen, causing osmotic (watery) diarrhoea
Bacterial gastroenteritis has multiple mechanisms:
1. Enterotoxins -produced by some bacterial species - adhere to intestinal mucosa without invading, impairing intestinal absorption and cause secretion of electrolytes and water by stimulating adenylate cyclase, resulting in watery diarrhoea
2. Exotoxins are ingested in contaminated food - causing gastroenteritis without bacterial infection - symptoms abate w/i 36 hours
3. Mucosal invasion occurs with other bacteria , invading mucosa of small bowel , causing ulceration, bleeding, exudation of protein-rich fluid and secretion of water & electrolytes. Resulting diarrhoea has leukocytes and RBCs present on microscopy
71
Signs and symptoms of gastroenteritis
Sudden onset:
- Anorexia
- Nausea
- Vomiting
- Abdominal cramps
- Diarrhoea
- Abdomen may be distended or tender
- Muscle guarding in abdomen
- Possible gas-distended intestinal loops may be palpable
- Hyperactive bowel sounds on auscultation
72
Risk factors for gastroenteritis
- Contaminated food
| - Immunodeficiencies
73
Diagnosis of gastroenteritis
- Stool sample
- Physical examination
- Sigmoidoscopy
74
Treatment for gastroenteritis
- Oral or IV rehydration
- Antidiarrhoeal agents (not in children or bacterial gastroenteritis)
- Antibiotics (in some cases)
