14. Mucosal defence and response to injury Flashcards
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
what do REGENERATING PROTEINS do in RESTITUTION
(from ECL and Enteroendocrine cells that are close to injury)
Help structurally ORGANISE EPITHELIUM
what do TREFOIL PEPTIDES do
stimulate CELL motility and MIGRATION
secreted along with mucus to help PRODUCE BARRIER
how does GASTRIN help DEFENCE
- promotes CELL MIGRATION and cell growth
- INCREASES MUCUS and HCO3- production
- Promotes release of GROWTH FACTORS - facilitate new epithelial cell growth
what are PEYER’S PATCHES
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
FOLLICLE ASSOCIATE EPITHELIUM which lines dome over PEYER’S PATCH contains which CELLS
MICROFOLD CELLS (M CELLS)
what do MICROFOLD (M) CELLS do
TRANSPORT BACTERIA/ANTIGENS/PARTICLES
to basolateral pocket where they are PRESENTED to IMMUNE SURVEILLANCE CELLS
what overlies M CELLS
THIN mucus layer
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)
- INNERVATION in GUT WALL
- increase MOTILITY to MOVE Infectious agents away to be removed by LI - Stimulate MUCUS PRODUCTION for barrier against pathogenic attack
- increase expression pro-inflammatory CYTOKINES
CYTOKINES release in PEYER’S PATCHES causes:
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
which ANTIBODY is SECRETED by PEYER’S PATCHES
IgA
How is IgA in GUT LUMEN PROTECTED from DIGESTION
has ATTACHED SECRETORY COMPONENT
what happens as ENTEROCYTE cells MOVE UP CRYPT-VILLUS AXIS
From STEM CELLS in CRYPT
DIFFERENTIATE and become more SPECIALISED for ABSORPTION (transporters)
at top of villus: OLD cells SHED
- REGULAR REPLACEMENT and RENEWAL
what can you find in CRYPT with STEM CELLS
PANETH CELLS
- secrete CRYPIDINS and DEFENSINS which attack bacteria to prevent damage to stem cells
(PROTECT STEM CELLS)
how many CRYPTS PER VILLUS
6-10
how many CRYPT CELLS
250
how many VILLUS CELLS
3500
how many CELLS are LOST/SHED PER VILLUS PER DAY
1400 cells /villus/day
what happens to DAMAGED CELLS
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
what happens to the BARRIER as CELLS SHED
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
how long do cells take to SHED
10 MINUTES
WHERE is the VOMITING CENTRE
in MEDULLA OBLONGATA
what can stimulate SIGNALS FROM GUT via AFFERENT fibres to VOMITING CENTRE
pain, bloating, inflammation, irritants, toxins etc
EFFERENT FIRES from VOMITING REFLEX act on
OESOPHAGUS,
DIAPHRAGM,
INTERCOSTAL MUSCLES,
PYLORIS,
ANTRUM,
DUODENUM
in VOMITING REFLEX, PHRENIC NERVE to DIAPHRAGM causes …
diaphragm to be FIXED FOR INSPIRATION
VOMITING REFLEX action on INTERCOSTAL MUSCLES
CONTRACT
- create HIGH INTRABDOMINAL muscular PRESSURE
VOMITING REFLEX action via VAGUS NERVE on DUODENUM, PYLORIS, ANTRUM
CONTRACT
stop food going further down
VOMITING REFLEX action on LOWER OESOPHAGEAL SPHINCTER, UPPER OESOPHAGEL SPHINCTER, PHARYNX
RELAX
- so only way for food to go is up
(soft palate raised and epiglottis moves over trachea)
CONTRACTION of INTERCOSTAL MUSCLES in VOMITING REFLEX creates what
HIGH ABDOMINAL PRESSURE
- needed for reflex
what RELAX in VOMITING REFLEX
LOS, UOS, PHARYNX
what CONTRACT in VOMITING REFLEX
DUODENUM, PYLORIS, ANTRUM (stomach)
INTERCOSTAL MUSCLES
how is PRESSURE in VOMITING REFLEX
HIGH ABDOMINAL MUSCULAR PRESSURE
