14. Mucosal defence and response to injury Flashcards
(55 cards)
DAMAGING FACTORS in the GUT
- 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
PROTECTIVE FACTORS in the GUT against damage
- 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
DEFENCE MECHANISMS against ACID and PEPSIN in STOMACH
- 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
what is MUCUS made up of
MUCINS
- large mucus GLYCOPROTEINS
MUCINS STRUCTURE
linked together by Disulphide bonds
heavily GLYCOSYLATED
- PROTECTION for PROTEIN CORE from PROTEASE ATTACK
PROSTAGLANDINS come from..
ARACHIDONIC ACID
- from PHOSPHOLIPIDS in membrane
by COX-1 ENZYME
INFLAMMATORY STIMULUS / INJURY induces PROSTAGLANDINS via which ENZYME
COX-2
FUNCTIONS of PROSTAGLANDINS in epithelial defence
- 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
PROSTAGLANDINS INCREASE:
- HCO3- and MUCUS
- BLOOD FLOW
- EPITHELIAL RESTITUTION (cell MIGRATION)
PROSTAGLANDINS INHIBIT:
- HISTAMINE SECRETION (ECL cells)
- ACID SECRETION (parietal cells)
EXOCRINE PANCREASE produces … to NEUTRALISE ACIDIC STOMACH CHYME
BICARBONATE, HCO3-
HCO3- RELEASE from which cells
DUCT CELLS
what is the result of activation of STRETCH RECEPTORS in DUODENUM from food
afferent -> vagus nerve -> brain stem -> efferent -> PANCREAS
- ACH stimulates ENZYME PRODUCTION from ACINAR CELLS
- VIP stimulates HCO3- RELEASE from DUCT CELLS
when I and K cells in DUODENUM SENSE FATS and PROTEINS, what do they RELEASE
I: CCK on ACINAR CELLS (enzymes)
K: VIP on DUCT CELLS (HCO3-)
S CELLS of DUODENUM SENSE ACID and SECRETE:
SECRETIN
-> DUCT CELLS for HCO3- release
what does SECRETIN Act on and what does it stimulate RELEASE of
DUCT CELLS
also GALLBLADDER DUCTS and HEPATIC DUCTS
-> HCO3- RELEASE
ACH acts on which CELLS
PANCREATIC ACINAR CELLS for ENZYME production
VIP acts on which PANCREATIC CELLS
DUCT CELLS
what is the RESPONSE to PENETRATING ACID (through mucosa)
INCREASED BLOOD FLOW
- HYPERAEMIA
to CLEAR away H+
and increase nutrients and oxygen to repair any damage
when CHEMO-SENSITIVE NERVES DETECT H+ coming through Mucosa, what does it cause RELEASE of from EFFERENT FIBRES
RELAXING FACTORS:
CGRP (calcitonin gene related peptide)
NO (nitric oxide)
what do RELAXING FACTORS CGRP and NO cause in response to PENETRATING ACID
DILATES Smooth muscle of BLOOD VESSELS
to INCREASE BLOOD FLOW
what is also RELEASED as a result of INCREASED ACID
SOMATOSTATIN
- turns OFF acid and pepsinogen secretion
what is RESTITUTION
RAPID, REPAIR MECHANISMS to DAMAGED EPITHELIUM
- CELL MIGRATION
RESTORED functional epithelium although THINNER
key players in the REPAIR of DAMAGED EPITHELIUM (RESTITUTION)
- GASTRIN
-> GROWTH FACTORS - PROSTAGLANDINS (increase cell migration and blood flow)
- REGENERATING PROTEIN (REG)
- TREFOIL PEPTIDES
