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PHYL2064 > GIT L4: GIT pathophysiology (IBD) and pharmacology > Flashcards

GIT L4: GIT pathophysiology (IBD) and pharmacology Flashcards

1
Q

What part of the GIT is important for mechanical digestion?

A

Stomach

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2
Q

What part of the GIT is important for absorption of nutrients?

A

Small intestine

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3
Q

What is inflammatory bowel disease (IBD) defined as?

A

chronic intestinal inflammation that results from immunological abnormalities and triggered by genetic and environmental factors

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4
Q

The inflammatory bowel diseases (IBD) are defined as ________ that results from _______ and triggered by _____ and ______ factors

A

chronic intestinal inflammation; immunological abnormalities; genetic; environmental

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5
Q

What are the 2 forms of IBD?

A
  1. Ulcerative colitis (UC)
  2. Crohn’s disease (CD),
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6
Q

What are immunological abnormalities?

A

Immune system starts attacking parts of the GIT

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7
Q

While they know that immunological abnormalities and genetic and environmental factors increases the risk, IBD is an ____ disease

A

idiopathic

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8
Q

What are 2 ways to differentiate between ulcerative colitis (UC) and Crohn’s disease which are both IBDs?

A
  1. Location of the inflammation in the GIT
  2. Nature of the alterations in the intestinal wall.
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9
Q

What is ulcerative colitis (UC)?

A

causes long-lasting inflammation and sores (ulcers) in the innermost lining of large intestine (colon &rectum).

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10
Q

Where does ulcerative colitis (UC) affect?

A

innermost lining of large intestine (colon & rectum)- muscosa

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11
Q

What is Crohn’s disease?

A

cause chronic inflammation that often spreads deep into affected tissues (transmural) – fistula formation.

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12
Q

Where does Crohn’s disease affect?

A

deep into affected tissues (transmural- submucosa).

Any part of the GIT- most common in the small and large intestines

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13
Q

What does ulcerative colitis (UC) cause?

A

causes long-lasting inflammation and sores

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14
Q

What does Crohn’s disease cause?

A

cause chronic inflammation

Deeper fissure, open wounds

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15
Q

How to test whether you have any IBD?

A

Endoscopy & Histopathology

  • Specimens and take to the lab
  • Once had a gastroscopy and tested the histological specimen –> will be diagnosed with either
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16
Q

People with Crohn’s Disease have ___ (thickened/thinner) walls.

A

thicken

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17
Q

Why do people with Crohn’s Disease have thickened walls?

A
  • Constant inflammation
  • System tries to compensate by thickening the walls of the GIT (more immune cells in the area)
  • Deep effect of submucosa –> drives cobblestoning
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18
Q

People with UC (ulcerative colitis) have ___ (thickened/thinner) walls.

A

thinner

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19
Q

Why do people with ulcerative colitis (UC) have thinner walls?

A

Very superficial changes of mucosa (polyps)

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20
Q

What are the 2 main differences in those areas? (high and low increase)

A
  1. Areas where processed food is heavily used/consumes are areas that have a high incidence rate of IBD
    • Environmental factors
      • Extra additives might trigger a response within GIT
      • Level of the muscosa- lots of cells (esp. small and large intestine) which are important to absorb certain nutrients = blood is constantly in contact with these added additives (which might not be good enough for our body to produce energy) and somehow activate white blood cells
  2. More industrialised, more stress in the area = higher incidence rates
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21
Q

What are 6 signs and symptoms of IBD?

A
  1. Abdominal pain and cramping
  2. Reduced appetite
  3. Unintended weight loss
  4. Diarrhoea
  5. Blood in stool
  6. Unexplained fever lasting > 1-2 days
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22
Q

Why is it important to not let IBD go untreated?

A

impact on external parts of GIT

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23
Q

If left untreated, how does IBD have an impact on external parts of the GIT?

A
  • If you have a constant immune system that is activated against part of your body (eg. muscosa of the large intestine), there is a risk that the immune system will overeact to other part of the body
  • If constantly attacked part of the GIT that is important for the absorption of food, less food absorbed (eg. in small intestine- nutrients/large intestine- minerals) –> can have secondary consequences than IBD (could arise from IBD)
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24
Q

What are 6 systems that can be affected by the extraintestinal manifestations of IBD?

A
  1. musculoskeletal
  2. dermatologic
  3. hepatopancreatobiliary
  4. ocular
  5. renal
  6. pulmonary
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25
Q

What are 3 ways to diagnose IBD?

A
  1. Clinical signs
  2. Haematology, Endoscopy, Radiology
  3. Need to exclude enteric infections!
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26
Q

What is antibiotics used for in IBD?

A

Can take antibiotics (if mild- not IBD) or more complex to manage the chronic inflammation (difficult to get rid off)

27
Q

While the exact cause of IBD is unclear (idiopathic), what are 4 main factors that influence the disease?

A
  1. Host genetic susceptibility
  2. A dysregulated immune response
  3. Impairment of intestinal epithelial barrier function, and
  4. Environmental factors
28
Q

What are 3 ways why the immune response is related to IBD?

A
  1. Overactivated
  2. Other parts driving immune system to respond (eg. virus)
  3. Starts attacking part of GIT
29
Q

What are 2 ways of how the impairment of the barrier affects IBD?

A
  1. Damaged or opening up wounds (eg. Trauma)
  2. Call immune system to help with damage = can cause problems
30
Q

What are 3 environmental factors that influence IBD?

A
  1. Stress
  2. Pollution
  3. Antibiotics
31
Q

Why does antibiotics (environmental factor) influence IBD?

A
  • Some friendly bacteria in large intestine –> kills any bacteria even the good ones in the GIT
  • Once good bacteria killed by antibiotics –> pathogen can start to take over the area (colonise area) –> need immune system to be activated –> impaired barrier function —> IBD
32
Q

What are 4 risk factors for IBD?

A
  1. Age
    • Usually diagnosis < age 30 years, sometimes 50s or 60s.
  2. Family history
    • Higher risk if close relative with IBD
  3. Nonsteroidal anti-inflammatory medications
    • May increase the risk of developing IBD or worsen disease in people who have IBD.
    • Role of housekeeping PG
  4. Geography
    • Higher incidence in urban area, industrialized
    • Country, Northern climate
33
Q

What is a protective factor for IBD?

A

Cigarette smoking (nicotine)

  • Smoking has been shown to help patients with ulcerative colitis!
34
Q

How is family history a risk factor for IBD?

A

Higher risk if close relative with IBD (Genetic mutation)

35
Q

How is non-steroidal anti-inflammatory medications a risk factor for IBD?

A
  • May increase the risk of developing IBD or worsen disease in people who have IBD.
  • Long term use could have an effect on the mucosa
  • Role of housekeeping PG (Prostaglandins in the area)
36
Q

How is Geography a risk factor for IBD?

A

Higher incidence in urban area, industrialized

Country, Northern climate

37
Q

How is age a risk factor for IBD?

A

Usually diagnosis < age 30 years (Higher chance), sometimes 50s or 60s.

38
Q

Why are northern/colder climates a risk factor for IBD?

A

Colder countries over warmer countries

  • Due to food
    • Warmer country = lighter food
    • Colder country = heavier food
39
Q

What are 2 characteristics of the pathogenesis of IBD?

A
  1. An abnormal immune response.
  2. Disturbance in the balance between gut commensal bacteria & host response in the intestinal mucosa.
40
Q

_____ cells play a prominent role in the pathogenesis of IBD.

A

Epithelial

41
Q

What are the 4 steps that occur in the pathogenesis of IBD?

A
  1. Impaired barrier function
    • Not as good as normal
    • Physical damage of the barrier –> pathogens cross the barrier into submucosa layer
  2. Activate the immune system response
    • White blood cells are called
    • Overreacted (failure of some white blood cells to stop this overreaction) = lose the regulation of the immune system = higher production of inflammatory mediations = more white blood cells
  3. Pathogenesis Rise of IBD
42
Q

In the 5 approaches to pharmacological therapy for IBD, which way do you treat? Why?

A

Try to reduce the symptoms starting bottom (mild) to top (more extreme management) increased side effects as well

43
Q

When do you start from top to bottom in the 5 approaches ? What are the complications?

A
  • Sometimes the symptoms/ effects of IBD can be so severe that they start from top to bottom (need to remove immune activation)
  • Not the preferred method
    • Surgery –> Removal of part of GIT –> removal of something that has an important function
    • But able to survive and have less symptoms (this is better than not removing, but will still affect life so better to start bottom to top)
44
Q

What is the cure for IBD?

A

No cure

45
Q

What is the goal of IBD treatment?

A

reduce the inflammation.

46
Q

In the treatment of IBD, it is important to understand & maintain links between _____ and the _____ & bacteria in the GIT (microbiome).

A

diet; immune system

47
Q

How can diet be helpful as treatment?

A

Might be a chronic diet (no longer able to have certain foods which aggravate symptoms)

48
Q

What are 3 things that treatment for IBD leads to?

A
  1. symptom relief
  2. long-term remission
  3. reduced risks of complications.
49
Q

What are 3 options for drug therapy or surgery?

A
  1. Anti-inflammatory drugs:
    • Aminosalicylates, corticosteroids.
  2. Immunomodulators (immunesuppressors)
    • Azathioprine , mercaptopurine
    • Cyclosporine
  3. Biological therapy (TNF-a inhibitors)
50
Q

Why should treatment target tumour necrosis factor (TNF)?

DO NOT NEED TO KNOW SPECIFIC

A

TNF-specific antibodies may alleviate disease by simultaneously suppressing several pro-inflammatory pathways in patients with IBD.

51
Q

Stem-cell therapy through ______ or _______ is a promising therapeutic option for severe refractory cases especially when surgery is not feasible.

A

hematopoietic stem cells (HSCs); mesenchymal stem /stromal cells (MSCs)

52
Q

In perianal Crohn’s disease (CD), what is the objective in stem cell therapy?

A

deposit MSCs locally in fistulising tracts to down-regulate the local immune response and induce wound healing.

53
Q

In HSC transplantation, what is the objective in stem cell therapy?

A

destroy the ‘autoreactive’ immune cells responsible for disease chronicity, and to re-establish gut tolerance to gut microbes.

54
Q

How does stem cell therapy directly impact the walls of the GIT?

A

Close off the mucosa to the submuscosa (close the path for pathogen) = decrease immune system

Eventually the body will heal itself

55
Q

______is a first go to treatment before surgery in Crohn’s disease to try and reduce the inflammation.

A

Stem cell therapy

56
Q

What is Fecal microbiota transplantation (FMT)?

A

stool transplant

57
Q

How does Fecal microbiota transplantation (FMT) work?

A

introducing fecal bacteria (stool) from an healthy individual into the affected patient to restore the colonic microflora.

58
Q

Fecal microbiota transplantation (FMT) was Originally used to treat patients suffering _______ infection (CDI)

A

Clostridium difficile

59
Q

Fecal microbiota transplantation (FMT) is recently being used in patients with _______ to treat the symptoms. Very early stages, but the preliminary data shows interesting results, even without knowing how it works! Speculation on restoring the “normal dialog” between _____ and _____ system.

A

IBD; gut microbes; immune

60
Q

Why would Fecal microbiota transplantation (FMT) work?

A
  • Different bacteria are found in the large intestine
  • Harvesting good bacteria from a healthy donor –> re-introduce them to the IBD patient Help to reduce inflammation
61
Q

The stool specimens have procedures to make sure they only___ the bacteria that is important and then it is introduce into large intestine of IBD patient

A

isolate

62
Q

What is the benefit of Fecal microbiota transplantation (FMT), while it sounds disguising?

A

least invasive procedure to reduce symptoms (quite effective)

63
Q

When is someone diagnosed with IBS?

A
  • Checked for everything and all negative (eliminated all others)
  • But still have problems with intestines
  • Possible relationship with enteric nervous system (dysregulated from autonomic NS)
  • Pain and bloating
  • Stress related (enteric NS)

PHYL2064 (29 decks)

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