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Gastrointestinal > 14. Mucosal defence and response to injury > Flashcards

14. Mucosal defence and response to injury Flashcards

1
Q

DAMAGING FACTORS in the GUT

A
  • ACID and PEPSIN (harsh environment, low pH)
  • ingested DRUGS (alcohol,aspirin..)
  • REFLUXED BILE
  • SMOKING
  • MICRO-ORGANISMS (eg H. Pylori)
  • ISCHEMIA (OXIDATIVE STATE) - reduced blood flow
  • Food ALLERGENS
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2
Q

PROTECTIVE FACTORS in the GUT against damage

A
  • MUCUS-HCO3 BARRIER overlying epithelial surface
  • Cell MEMBRANE - tougher where needed ie stomach, duodenum (acid and pepsin)
  • Cell MIGRATION to area of damage and constant RENEWAL (high turnover)
  • Mucosal BLOOD FLOW - brings O2 and nutrients for repair, clears harmful substances
  • PROSTAGLANDINS
  • IMMUNE SYSTEM
  • ACID INHIBITION (ie blocking H+ Pump, block H2 Receptor from histamine binding)
  • PROGRAMMED CELL DEATH
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3
Q

DEFENCE MECHANISMS against ACID and PEPSIN in STOMACH

A
  • DIFFUSION BARRIER:
    MUCUS-HCO3- barrier & TIGHT JUNCTIONS (very tight) between cells SLOW H+ DIFFUSION

-Cell surface PHOSPHOLIPIDS (tougher barrier)

  • PHYSICAL BARRIER against PROTEOLYTIC ATTACK
  • CELL MIGRATION and REGENERATION
  • BLOOD SUPPLY CARRIES H+ AWAY if do permeate, helps ANTIOXIDANT FUNCTION
  • Mucosal PROSTAGLANDINS drive HCO3- production and increase blood flow
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4
Q

what is MUCUS made up of

A

MUCINS
- large mucus GLYCOPROTEINS

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5
Q

MUCINS STRUCTURE

A

linked together by Disulphide bonds

heavily GLYCOSYLATED
- PROTECTION for PROTEIN CORE from PROTEASE ATTACK

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6
Q

PROSTAGLANDINS come from..

A

ARACHIDONIC ACID

  • from PHOSPHOLIPIDS in membrane
    by COX-1 ENZYME
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7
Q

INFLAMMATORY STIMULUS / INJURY induces PROSTAGLANDINS via which ENZYME

A

COX-2

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8
Q

FUNCTIONS of PROSTAGLANDINS in epithelial defence

A
  • REGULATE RELEASE of mucosal HCO3- and MUCUS
  • INCREASE / maintain mucosal BLOOD FLOW and EPITHELIAL RESTITUTION (enhance motility/movement of cells to repair damage)
  • INHIBIT HISTAMINE RELEASE from ECL CELLS
  • INHIBIT ACID SECRETION from PARIETAL CELLS
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9
Q

PROSTAGLANDINS INCREASE:

A
  • HCO3- and MUCUS
  • BLOOD FLOW
  • EPITHELIAL RESTITUTION (cell MIGRATION)
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10
Q

PROSTAGLANDINS INHIBIT:

A
  • HISTAMINE SECRETION (ECL cells)
  • ACID SECRETION (parietal cells)
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11
Q

EXOCRINE PANCREASE produces … to NEUTRALISE ACIDIC STOMACH CHYME

A

BICARBONATE, HCO3-

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12
Q

HCO3- RELEASE from which cells

A

DUCT CELLS

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13
Q

what is the result of activation of STRETCH RECEPTORS in DUODENUM from food

A

afferent -> vagus nerve -> brain stem -> efferent -> PANCREAS

  • ACH stimulates ENZYME PRODUCTION from ACINAR CELLS
  • VIP stimulates HCO3- RELEASE from DUCT CELLS
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14
Q

when I and K cells in DUODENUM SENSE FATS and PROTEINS, what do they RELEASE

A

I: CCK on ACINAR CELLS (enzymes)
K: VIP on DUCT CELLS (HCO3-)

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15
Q

S CELLS of DUODENUM SENSE ACID and SECRETE:

A

SECRETIN

-> DUCT CELLS for HCO3- release

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16
Q

what does SECRETIN Act on and what does it stimulate RELEASE of

A

DUCT CELLS

also GALLBLADDER DUCTS and HEPATIC DUCTS

-> HCO3- RELEASE

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17
Q

ACH acts on which CELLS

A

PANCREATIC ACINAR CELLS for ENZYME production

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18
Q

VIP acts on which PANCREATIC CELLS

A

DUCT CELLS

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19
Q

what is the RESPONSE to PENETRATING ACID (through mucosa)

A

INCREASED BLOOD FLOW
- HYPERAEMIA

to CLEAR away H+
and increase nutrients and oxygen to repair any damage

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20
Q

when CHEMO-SENSITIVE NERVES DETECT H+ coming through Mucosa, what does it cause RELEASE of from EFFERENT FIBRES

A

RELAXING FACTORS:
CGRP (calcitonin gene related peptide)
NO (nitric oxide)

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21
Q

what do RELAXING FACTORS CGRP and NO cause in response to PENETRATING ACID

A

DILATES Smooth muscle of BLOOD VESSELS

to INCREASE BLOOD FLOW

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22
Q

what is also RELEASED as a result of INCREASED ACID

A

SOMATOSTATIN
- turns OFF acid and pepsinogen secretion

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23
Q

what is RESTITUTION

A

RAPID, REPAIR MECHANISMS to DAMAGED EPITHELIUM
- CELL MIGRATION

RESTORED functional epithelium although THINNER

24
Q

key players in the REPAIR of DAMAGED EPITHELIUM (RESTITUTION)

A
  • GASTRIN
    -> GROWTH FACTORS
  • PROSTAGLANDINS (increase cell migration and blood flow)
  • REGENERATING PROTEIN (REG)
  • TREFOIL PEPTIDES
25
Q

what do REGENERATING PROTEINS do in RESTITUTION
(from ECL and Enteroendocrine cells that are close to injury)

A

Help structurally ORGANISE EPITHELIUM

26
Q

what do TREFOIL PEPTIDES do

A

stimulate CELL motility and MIGRATION

secreted along with mucus to help PRODUCE BARRIER

27
Q

how does GASTRIN help DEFENCE

A
  • promotes CELL MIGRATION and cell growth
  • INCREASES MUCUS and HCO3- production
  • Promotes release of GROWTH FACTORS - facilitate new epithelial cell growth
28
Q

what are PEYER’S PATCHES

A

GUT IMMUNE SYSTEM:
LYMPHOID tissue in the wall of the SMALL INTESTINE which are involved in the development of IMMUNITY to antigens

In DISTAL ILEUM

29
Q

FOLLICLE ASSOCIATE EPITHELIUM which lines dome over PEYER’S PATCH contains which CELLS

A

MICROFOLD CELLS (M CELLS)

30
Q

what do MICROFOLD (M) CELLS do

A

TRANSPORT BACTERIA/ANTIGENS/PARTICLES

to basolateral pocket where they are PRESENTED to IMMUNE SURVEILLANCE CELLS

31
Q

what overlies M CELLS

A

THIN mucus layer

32
Q

ANTIGENS are trasported in tact via M CELLS where they are recognised by IMMUNE SURVEILLANCE CELLS (ie mast cells, macrophages, T cells, intestinal intraepithelial lymphocytes IEL)

what does this ACTIVATE (3)

A
  1. INNERVATION in GUT WALL
    - increase MOTILITY to MOVE Infectious agents away to be removed by LI
  2. Stimulate MUCUS PRODUCTION for barrier against pathogenic attack
  3. increase expression pro-inflammatory CYTOKINES
33
Q

CYTOKINES release in PEYER’S PATCHES causes:

A

cellular and humoral responses
- T and B cells, ANTIBODY production

-> IgA PRODUCTION
- transported via M CELLS where Bind microorganisms/antigens in gut lumen or m cell

34
Q

which ANTIBODY is SECRETED by PEYER’S PATCHES

A

IgA

35
Q

How is IgA in GUT LUMEN PROTECTED from DIGESTION

A

has ATTACHED SECRETORY COMPONENT

36
Q

what happens as ENTEROCYTE cells MOVE UP CRYPT-VILLUS AXIS

A

From STEM CELLS in CRYPT

DIFFERENTIATE and become more SPECIALISED for ABSORPTION (transporters)

at top of villus: OLD cells SHED

  • REGULAR REPLACEMENT and RENEWAL
37
Q

what can you find in CRYPT with STEM CELLS

A

PANETH CELLS
- secrete CRYPIDINS and DEFENSINS which attack bacteria to prevent damage to stem cells
(PROTECT STEM CELLS)

38
Q

how many CRYPTS PER VILLUS

A

6-10

39
Q

how many CRYPT CELLS

A

250

40
Q

how many VILLUS CELLS

A

3500

41
Q

how many CELLS are LOST/SHED PER VILLUS PER DAY

A

1400 cells /villus/day

42
Q

what happens to DAMAGED CELLS

A

APOPTOSIS - programmed cell death

shrink, bleb, mitochondria breakdown, enzyme cascade to breakdown DNA and proteins, membrane Flipsm draws in Immune surveillance cells which Engulf and remove

43
Q

what happens to the BARRIER as CELLS SHED

A

MAINTAINED by ZIPPER MECHANISM

  • cells detach from basement membrane and apical movement of extruding epithelial cells

-> REARRANGEMENT of TIGHT JUNCTIONS so no gaps in barrier

44
Q

how long do cells take to SHED

A

10 MINUTES

45
Q

WHERE is the VOMITING CENTRE

A

in MEDULLA OBLONGATA

46
Q

what can stimulate SIGNALS FROM GUT via AFFERENT fibres to VOMITING CENTRE

A

pain, bloating, inflammation, irritants, toxins etc

47
Q

EFFERENT FIRES from VOMITING REFLEX act on

A

OESOPHAGUS,
DIAPHRAGM,
INTERCOSTAL MUSCLES,
PYLORIS,
ANTRUM,
DUODENUM

48
Q

in VOMITING REFLEX, PHRENIC NERVE to DIAPHRAGM causes …

A

diaphragm to be FIXED FOR INSPIRATION

49
Q

VOMITING REFLEX action on INTERCOSTAL MUSCLES

A

CONTRACT
- create HIGH INTRABDOMINAL muscular PRESSURE

50
Q

VOMITING REFLEX action via VAGUS NERVE on DUODENUM, PYLORIS, ANTRUM

A

CONTRACT

stop food going further down

51
Q

VOMITING REFLEX action on LOWER OESOPHAGEAL SPHINCTER, UPPER OESOPHAGEL SPHINCTER, PHARYNX

A

RELAX

  • so only way for food to go is up
    (soft palate raised and epiglottis moves over trachea)
52
Q

CONTRACTION of INTERCOSTAL MUSCLES in VOMITING REFLEX creates what

A

HIGH ABDOMINAL PRESSURE
- needed for reflex

53
Q

what RELAX in VOMITING REFLEX

A

LOS, UOS, PHARYNX

54
Q

what CONTRACT in VOMITING REFLEX

A

DUODENUM, PYLORIS, ANTRUM (stomach)

INTERCOSTAL MUSCLES

55
Q

how is PRESSURE in VOMITING REFLEX

A

HIGH ABDOMINAL MUSCULAR PRESSURE

Gastrointestinal (19 decks)

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