Physiology Flashcards
- Peters lecture - Introduction to the structure of the gi tract and motility - Physiology of gastric motility, secretion and digestion – Prof J Peters (200 cards)
1
Q
What separates the series of hollow organs which make up the alimentary canal?
A
Sphincters controlling movement
2
Q
What is the direction of movement through the alimentary canal?
A
oral to aboral, mouth to anus
3
Q
What is the function of the mouth and oropharynx?
A
to chop and lubricate food
begin carbohydrate digestion
deliver food to the oesophagus
4
Q
What is the function of the oesophagus?
A
to propel food to the stomach
5
Q
What is the function of the stomach?
A
stores/ churns food
continues carbohydrate digestion
begins protein digestion
regulates delivery of chyme (the product of digestion in the stomach) into the duodenum through the sphincter
6
Q
What are the 3 parts of the small intestine?
A
the duodenum, jejunum and ileum
7
Q
What is the function of the small intestine?
A
principal site of digestion and absorption of nutrients
8
Q
What are the 3 parts which make up the large intestine?
A
caecum, appendix and colon
9
Q
What is the function of the colon?
A
reabsorbs fluids and electrolytes
stores faecal matter before delivery to the rectum
can also do some limited digestion and absorption e.g. Vitamin K
10
Q
What are the 2 parts of the rectum?
A
the sigmoid and descending
11
Q
What are the 3 parts of the colon?
A
ascending, transverse and descending
12
Q
What is the function of the rectum and anus?
A
regulated expulsion of faeces
13
Q
What is the mechanism which moves the food down the oesophagus?
A
perastalsis
14
Q
What are the accessory structures of the alimentary canal?
A
salivary glands
the pancreas
the liver and gall bladder (hepatobiliary)
15
Q
What are the 4 general layers of the digestive tract wall?
A
mucosa (IM)
submucosa
muscularis externa
serosa (OM)
16
Q
What are the characteristics of the mucosa layer in the general digestive tract wall?
A
has a mucous membrane (epithelial, exocrine gland and endocrine gland cells) (IM) lamina propria (capillaries, enteric neurones, gut-associated lymphoid tissue) muscularis mucosae (OM)
17
Q
What are the characteristics of the submucosa layer in the general digestive tract wall?
A
connective tissue
larger blood & lymph vessels
glands
submucous plexus (neurone network
18
Q
What are the characteristics of the muscularis externa layer in the general digestive tract wall?
A
Circular muscle layer myenteric plexus (neurone network longitudinal muscle layer
19
Q
What are the characteristics of the serosa layer in the general digestive tract wall?
A
connective tissue
20
Q
What are the major functions of the alimentary canal?
A
Motility
secretion
digestion
absorption
21
Q
What is motility of the alimentary canal?
A
mechanical activity mostly involving smooth muscle (skeletal muscle is involved at the mouth, upper oesophagus and external anal sphincter)
22
Q
What is secretion of the alimentary canal?
A
in response to the presence of food, hormonal and neural signals there is secretion from the digestive tract and its accessory structures into the lumen, for digestion and lubrication
23
Q
What is digestion in the alimentary canal?
A
chemical breakdown by enzymatic hydrolysis of complex foodstuffs to smaller, absorbable, units (physical digestion in the mouth, stomach and small intestine aids chemical digestion)
24
Q
What is absorption in the alimentary canal?
A
Transfer of the absorbable products of digestion (with water, electrolytes and vitamins) from the digestive tract to the blood, or lymph – largely mediated by numerous transport mechanisms
25
What are the 3 smooth muscular structures which are involved in GI motility?
circular muscle
longitudinal muscle
muscularis mucosae
26
What is the effect of circular muscle contraction on the lumen alimentary canal?
it becomes longer and narrower
27
What is the effect of the longitudinal muscle contaction on the lumen of the alimentary canal?
the lumen becomes shorter and wider
28
What is the effect of the musclaris mucosae contaction on the lumen of the alimentary canal?
change in absorptive and secretory area of mucosa (folding), mixing activity
29
How does electrical current flow through adjacent smooth muscle cells? What is the significance of this?
via the gap junctions which join the cells
this means that 100s of smooth muscle cells can be depolarized almost simultaneously as a synchronous wave and so the smooth muscle contracts as a single unit or sheet
30
What triggers depolarization of the smooth muscle in the GI tract wall?
specialized pacemaker cells modulated by
intrinsic (enteric) nerves
extrinsic (autonomic) nerves
numerous hormones
31
Where does spontaneous electrical activity in the smooth muscle occur as slow waves?
stomach
small intestine
large intestine
32
What does the term slow waves refer to in terms of smooth muscle?
rhythmic patterns of spontaneous membrane depolarization and repolarization that spread from cell to cell via gap junctions
33
What cells drive the slow waves in smooth muscle?
interstitial cells of Cajal (ICCs)
| these are pacemaker cells located largely between the circular and longitudinal muscle layers
34
What joins ICCs and smooth muscle cells?
gap junctions join ICCs to each other and smooth muscles which electrically couples them, the slow waves in ICCs drive slow waves in the smooth muscle cells coupled to them
Some ICCs also form a ‘bridge’ between nerve endings and smooth muscle cells
35
What makes a depolarizing slow wave result in smooth muscle contraction?
if the depolarization is not above threshold then there will be no action potential fired and therefore no muscle contraction.
The length of time the depolarization is above threshold also determines the number of action potentials which will be fired which has a direct correlation to the force of the contraction
36
What are the determinants of whether the slow wave's amplitude will above the threshold?
neuronal stimuli
hormonal stimuli
mechanical stimuli
Generally these stimuli act to depolarize smooth muscle cells rather than influence slow waves directly – depolarization shifts slow wave peak to threshold increases the level of depolarization the slow wave starts at
37
What parasympathetic nerves innervate the GI tract?
Preganglionic fibres which release ACh as they synapse with the ganglion cells within the enteric nervous system ENS
38
What are the excitatory influences of the parasympathetic nervous system on the GI tract?
increased gastric, pancreatic and small intestinal secretion, blood flow and smooth muscle contraction
39
What are the inhibitory influences of the parasympathetic nervous system on the GI tract?
relaxation of some sphincters, receptive relaxation of stomach
40
What are the inhibitory influences of the sympathetic nervous system on the GI tract?
Decreased motility, secretion and blood flow
41
What are the excitatory influences of the sympathetic nervous system on the GI tract?
Increased sphincter tone
42
What sympathetic nerves innervate the GI tract?
Preganglionic fibres (releasing ACh) synapse in the prevertebral ganglia. Postganglionic fibres (releasing NA) innervate mainly enteric neurones, but also other structures
43
What are the prevertebral ganglia that the preganglionic fibres supplying the GI tract synapse at?
Celiac
Superior mesenteric
inferior mesenteric
44
What does the Myenteric (Auerbach’s) plexus do?
mainly regulates motility and sphincters
45
What does the Submucous (Meissner’s) plexus do?
mainly modulates epithelia and blood vessels
46
Where is the majority of the GI tracts control from?
largely controlled intrinsically via reflex circuits which can operate independently
hormones and extrinsic nerves do however exert a strong regulatory influence
47
What are the 3 types of neurones which are part of the ENS?
```
sensory neurones e.g. mechanoreceptors, chemoreceptors, thermoreceptors
interneurones (the majority, co-ordinating reflexes and motor programs)
effector neurones (excitatory and inhibitory motor neurones supplying both smooth muscle layers, secretory epithelium, endocrine cells and blood vessels)
```
48
What is a local reflex?
sensory - interneurone - effector neurone all in the GI
| e.g. peristalsis
49
What is a short reflex?
the sensory and interneurone synapse at the prevertebral ganglion
e.g. intestino-intestinal inhibitory reflex (local distension activates sensory neurones exciting sympathetic pre-ganglionic fibres that cause inhibition of muscle activity in adjacent areas)
50
What is a long reflex?
the sensory neurone body is within the CNS and the sensory and neurone synapse at the vagus in the medulla
e.g. gastroileal reflex (increase in gastric activity causes increased propulsive activity in the terminal ileum)
this is a vago-vagal reflex both sensory and motor fibres are within the vagus nerve
51
What is satiation?
sensation of fullness generated during a meal, the signals increase during a meal to limit the meal size
52
What is perastalsis?
a wave of relaxation, followed by contraction, that normally proceeds a short distance along the gut in an aboral direction – triggered by distension of the gut wall
53
What is the process of perastalsis?
The distension of the gut wall activates the sensory neurones
This alters the activity of the interneurones and therefore alters the motorneurones
Behind the bolous the longitudinal muscle relaxes (release of VIP and NO from inhibitory motomeurone) and circular muscle contracts (release of ACh and substance P from the excitatory motoneurone)
In front of the bolous the longitudinal muscle contracts (release of ACh and substance P from excitatory motoneurone) and circular muscle relaxes (release of VIP and NO from inhibitory motoneurone)
54
What is haustration?
Occurs in the small intestine, due to segmentation - rhythmic contractions of the circular muscle layer that mix and divide luminal contents
55
what is colonic mass movement?
powerful sweeping contraction that forces faeces into the rectum – occurs a few times a day
56
what is migrating motor complex (MMC)?
powerful sweeping contraction from stomach to terminal ileum
57
What are the 6 sphincters in the GI tract?
```
Upper oesophageal sphincter (UOS)
Lower oesophageal sphincter (LOS)
Pyloric sphincter
Ileocaecal valve
Internal (smooth muscle) anal sphincter
External (skeletal muscle) anal sphincter
```
58
What is the function of the Upper oesophageal sphincter (UOS)?
(i) relaxes to allow swallowing, (ii) closes during inspiration
59
What is the function of the lower oesophageal sphincter (LOS)?
(i) relaxes to permit entry of food to the stomach, (ii) closes to prevent reflux of gastric contents to the oesophagus
60
What is the function of the Pyloric sphincter?
(i) regulates gastric emptying, (ii) usually prevents duodenal gastric reflux
61
What is the function of the Ileocaecal valve?
regulates flow from ileum to caecum (i) distension of ileum opens, distension of proximal colon closes
62
What is the function of the internal and external anal sphincters?
are regulated by the defaecation reflex and control defaecation
63
What region of the stomach expands to allow food in from the oesophagus?
orad region relaxes receptively (driven by vagus)
64
What's digestion occurs in the stomach?
digestion of proteins (by pepsin and HCl)
| carbohydrate digestion continues (by salivary amylase)
65
What is the function of the lower part of the body and the antrum of the stomach?
Mixes food with gastric secretions to produce semi-liquid chyme
66
What is the function of the orad stomach (fundas and proximal body)?
Storage in a constant state of tonic contraction
67
What is the function of the caudad stomach (distal body and antrum)?
has phasic contraction to mix the food to form chyme
68
What happens in the caudad region as a result of slow waves which reach threshold?
Phasic peristaltic contractions are driven by slow waves which reach threshold, they progress from midstomach to gastroduodenal junction (the antral wave, or pump).
This propels the contents towards pylorus (a very small volume of chyme flows into the duodenum in each contraction)
The velocity of contraction increases towards the junction, so the pyloric sphincter has closed before the chyme reaches it and so the chyme rebound back into the stomach - retropulsion this mixes the gastric contents making the particles which pass through the pylorus smaller
69
What are the gastric factors which determine the strength of the antral wave or pump?
The rate of the emptying is proportional to the volume in the stomach - the more distended the stomach is the greater the stretch of smooth muscle increasing stimulation of intrinsic nerve plexuses and increased vagus nerve activity and gastrin release
The thinner the chyme is the quicker the stomach empties
70
What are the duodenal factors which determine the strength of the antral wave or pump?
Delay of stomach emptying is achieved by
- enterogastric reflex, antral activity is decreased by intrnsic nerve plexuses and the ANS
- release of enterogastrones from the duodenum inhibits stomach contraction
71
What are the stimuli which drive neural and hormonal responses in the duodenum which delay stomach emptying?
Fat
Acid (to allow neutralisation of the gastric acid)
Hypertonicity (the products of digestion could potentially draw water out of the blood in the small intestine)
Distension
72
What happens in the orad region of the stomach?
when a swallow occurs the vagus drives relaxation of the orad and opening of the LOS - ingested material can therefor be stored
there is no slow wave activity, weak tonic contractions occur due to the thin musculature
The contents of the orad are intermittently propelled to the caudad region by tonic contractions (approx 1 min long)
73
What does the hormone gastrin do?
It decreases contractions and hence the rate of stomach emptying
74
what are the areas of the stomach in relation to the secretion of the mucosa?
the oxyntic gland area - the fundus and body
| the pyloric gland area - antrum
75
what compses the gastric mucosa?
- a surface lining the stomach
- pits ivaginations of the surface
- glands at the base of the pits which are responsible for several secretions
76
WHat cells are involved in secretion into the blood from the plyloric gland area?
D cells - secrete somatostatin
| G cells - secrete Gastrin
77
What cells are involved in secretion into the stomach from the oxantic mucosa?
Parietal cell - secretes hydrochloric acid, intrinsic factor & gastroferrin
Enterochromaffin-like cells - secrete histamine (which can act in a paracrine function)
Chief cells - secrete pepsinogen
78
What is the function of the HCl secreted into the stomach?
activates pepsinogen to pepsin
denatures protein
kills most (not all) micro-organisms ingested with food
79
What is the function of the pepsinogen secreted into the stomach?
inactive precursor of the peptidase, pepsin. Note: pepsin once formed activates pepsinogen (autocatalytic)
80
What is the function of the intrinsic factor and gastroferrin secreted into the stomach?
bind vitamin B12 and Fe2+ respectively, facilitating subsequent absorption
81
What is the function of histamine secreted into the stomach?
it stimulates the secretion of HCl
82
What is the function of mucous secreted into the stomach?
it has a protective function - protects the cells which make up the stomach wall
83
What is the function of gastrin secreted from the pyloricgland area into the blood?
stimulates HCl secretion
84
What is the function of somatostatin secreted from the pyloric gland area into the blood?
inhibits HCl secretion
85
What is the function of mucus secreted from the pyloric gland area into the stomach?
- it has a protective function - protects the walls that make up the stomach from being damaged by the digestive enzymes and the HCl
86
What are the 3 secretagogues which induce acid secretion from the parietal cell?
ACh
gastrin
histamine
- in the direct pathway these substances stimulate the parietal cell and cause H+ secretion into the lumen
- in the indirect pathway acetylcholine and gastrin stimuate the ELC and cause histamine release which stimulates the parietal cell
87
What signalling pathways do the stimulation of H+ secretion act on?
PLC - IP3 (gastrin, ACh)
cAMP - PKA (histamine) signalling pathways
(stimulate adenylate cyclase)
88
What signalling pathways do the inhibition of H+ secretion act on?
cAMP - PKA (somatostatin, prostaglandins) signalling pathways
(inhibit adenylate cyclase)
89
What are the 3 phases of gastric secretion?
Cephalic phase (‘in the head’) – before food reaches the stomach preparing it stomach to receive food
driven directly and indirectly by the CNS and vagus nerves (CN X)
Gastric phase – when food is in stomach
involves both physical and chemical mechanisms
Intestinal phase – after food has left stomach
chyme entering the upper small intestine causes weak stimulation of gastric section via neuronal and hormonal mechanisms (not discussed further)
90
What happens in the cephalic phase?
Vagus stimulates enteric neurones that:
release ACh directly activating parietal cells (neurotransmitter action)
via release of GRP causes release of gastrin from G cells in to systemic circulation that activates parietal cells (endocrine action)
via release of histamine from ECL cells that locally activates parietal cells (paracrine action)
via inhibition of D cells decreases the inhibitory effect of ss on G-cells
91
What happens in the Gastric phase?
distension of stomach activates reflexes that cause acid secretion
food buffers pH, D cell inhibition via ss of gastrin release is decreased
amino acids (e.g. tryptophan, phenylalanine) stimulate G cells. Other stimulants include: Ca2+, caffeine and alcohol
92
What helps to inhibit the cephalic phase?
vagal nerve activity decreases upon the cessation of eating and after stomach emptying - pain, nausea and negative emotions will decrease vagal nerve activity and therefore decrease gastric secretion
93
What helps to inhibit the gastric phase?
```
antral pH falls when food exits stomach (due to decreased buffering of gastric HCl) – release of somatostatin from D cells recommences, decreasing gastrin secretion
prostaglandin E2 (PGE2) continually secreted by the gastric mucosa acts locally to reduce histamine- and gastrin-mediated HCl secretion
```
94
What helps to inhibit the intestinal phase?
- same factors which reduce gastric mobility reduce gastric secretion at this stage - neural reflexes, enterogastrones
95
What are the lengths of the different ections of the small intestine?
duodenum – approx. 30 cm
jejunum – approx. 3.5 m
ileum – approx. 2.5 m
96
What is received by the small intestine?
chyme from the stomach - through the pyloric sphincter
pancreatic juice from the pancreas
bile from the liver and gall bladder through the sphincter of Oddi
97
What is the purpose of the motility of the smal intestine?
mixing of the chyme with digestive juices (segmentation)
slow propulsion of the chyme aborally (peristalsis)
removal of undigested residues to the large intestine via the ileocaecal valve (the migrating motor complex; MMC)
98
How is the surface area in the small intestine increased?
circular folds (of Kerckring)
villi
microvilli (the brush border)
99
What is segmentation in the small intestine?
- mixing when in the digestive state
- alternating contraction and relaxation of segments of circular muscle caused chopping which moves chyme back and forth vigorously after a meal
- duodenum has frequent segmentation contractions (12 per min), ileum has fewer (9 per min) net movement is slightly aboral
- movement through the small intestine is slow 3-5 hrs to allow absorption
100
What triggers segementation of the small intestine?
- pacemaker cells of the small intestine cause the BER which is continuous when at threshold it activates segmentation in response to distension
- parasympathetic stimulation increases strength of segmentation and sympathetic decreases
- in an empty ileum segmentation is triggered by gastrin from the stomach - gastroileal reflex
101
How does perastalisis in the interdigestive or fasting state occur?
- few localised contractions
- Migrating Motor Complex (MMC) - occurs every 90-120 minutes between meals, this is strong peristaltic contraction which slowly passes the length of the intestine and clears the debris, mucus and sloughed epithelial cells between meals.
- feeding and vagal activity inhibit MMC
- motilin triggers MMC (somtimes mimicked by macrolide antibiotics)
- gastrin and CCK inhibit MMC
102
What hormones are secreted by the small intestine into the blood?
- Gastrin - secreted by G cells of gastric antrum and duodenum
- Secretin - secreted by S cells in the duodenum in response to H+ and fatty acids in lumen
- Cholecystokinin (CCK) – secreted by I cells of duodenum and jejunum, in response to monoglycerides, free fatty acids, amino acids, small peptides in lumen
- Glucose-dependent insulinotropic peptide (GIP, aka gastric inhibitory peptide) - secreted by K cells of duodenum and jejunum, released in response to glucose, amino acid and fatty acids
- Glucagon-like peptide-1 (GLP-1) secreted by L cells of the small intestine
- Motilin – secreted by M cells of duodenum and jejunum, during fasting state
- Gherlin - secreted by Gr cells of the gastric antrum, small intestine and elsewhere (e.g. pancreas)
103
What is the function of Cholecystokinin (CCK)?
inhibits gastric emptying
causes secretion of pancreatic enzymes required for digestion
stimulates relaxation of sphincter of Oddi and contraction of gall bladder to eject bile into duodenum
potentiates the action of secretin
104
What is the function of Gastrin?
stimulates H+ secretion by gastric parietal cells & growth of gastric mucosa (a trophic effect)
105
What is the function of Secretin?
promotes secretion of pancreatic and biliary HCO3-
106
What is the function of
stimulates release of insulin from pancreatic β-cells (incretin action)
inhibits gastric emptying
107
What is the function of Glucagon-like peptide-1 (GLP-1)?
stimulates insulin secretion
inhibits glucagon secretion from pancreatic α-cells
decreases gastric emptying and appetite
108
What is the function of Motilin?
initiates the migrating motor complex
109
What is the function of Ghrelin?
stimulates appetite
110
What is succus entericus?
The juice which is secreted by the small intestine approx 2L per day
111
What does succus entericus contain?
No digestive enzymes
- mucus from the goblet cells for protection and lubrication
- aqueous salt from the crypts of lieberkuhn for enzymatic digestion
112
What stimulates and inhibits succus entericus release?
```
Increased by
Distension/irritation
gastrin
CCK
secretin
parasympathetic nerve activity
```
Decreased by
sympathetic nerve activity
113
What are the endocrine products of the pancreas?
insulin and glucagon
| secreted into the blood
114
What are the exocrine products of the pancreas?
digestive enzymes from the acinar cells
aqueous NaHCO3- solution from the duct cells
secreted to the duodenum collectively as pancreatic juice
115
What is the function of the pancreatic duct cells?
- secrete 1 – 2 litre of alkaline (HCO3- - rich) fluid into the duodenum per day. (the higher the secretion rates the higher the HCO3 content)
- This secretion neutralises acidic chyme entering the duodenum, to provide optimum pH for pancreatic enzyme function and protect the mucosa from acid
116
What are the 3 phases of pancreatic secretion?
Cephalic – mediated by the vagal stimulation of mainly the acinar cells (20% total secretion)
Gastric – gastric distension evokes a vagovagal reflex resulting in parasympathetic stimulation of acinar and duct cells (5-10% total secretion)
Intestinal (70-80% of total secretion)
- acid in the duodenum triggers increased release from S cells which goes to the pancreatic duct cells which increased NaHCO3 sol. into the duodenum
- fat and protein in the duodenum, increase CCK release from I cells, this goes to panreatic acinar cells and there is increased digestive enzyme secretion into the duodenal lumen
117
what are the 2 types of digestion which happen in the small intestine?
Luminal digestion – mediated by pancreatic enzymes secreted into the duodenum
Membrane digestion – mediated by enzymes situated at the brush border of epithelial cells
118
What is absorption in the digestive tract?
is the processes by which the absorbable products of digestion are transferred across both the apical and basolateral membranes of enterocytes (absorptive cells of the intestinal epithelium)
119
What is assimilation?
The overall process of digestion and absorption
120
What do all carbohydrates need to be converted to for absorption?
to monosaccharides - glucose, fructose or galactose
121
What are the 2 main polysaccharides obtained from plants in the diet?
Amylose and amylopectin
both are relatively straight chains of glucose monomers
amylose - alpha-1,4 linkage and amylopectin alpha-1,4 linkage (and alpha-1,6 linkage for branching)
122
What is the main polysaccharide obtained from animals in the diet?
glycogen
| it is much more branched that amylopectin
123
What are the steps of carbohydrate digestion?
Intraluminal hydrolysis
Membrane digestion
absorption
124
What enzyme is responsible for intraluminal hydrolysis?
alpha-amylase, from the salivary and pancreatic ducts
| polysaccharide (e.g. starch is broken down to oligosaccharides)
125
What is a oligosaccharide?
a carbohydrate molecule which can't be absorbed generally 2 monomers
sucrose and lactose are oligosaccharides we get from the diet (other e.g. α-limit dextrins, Maltotriose, Maltose)
126
What enzyme is responsible for membrane digestion (at the brush border)?
Oligosaccharidases
e.g. Lactase, Maltase & Sucrase-isomaltase
(two enzymes bound together)
(oligosaccharides
127
What is alpha-amylase?
An endoenzyme which breaks down linear alpha-1,4 linkages but not terminal alpha-1,4 linkages hence it doesn't produce glucose
cannot cleave α-1,6 linkages at branch points (in amylopectin) or α-1,4 linkages adjacent to branch points
products are thus linear glucose oligomers (maltotriose, maltose) and α-limit dextrins
128
What are oligosaccharidases?
integral membrane proteins with a catalytic domain that faces the lumen of the GI tract.
all oligosaccharidases cleave the terminal α-1,4 linkages of maltose, maltotriose and α-limit dextrins (to yield glucose) except for lactase which breaks lactose down
129
What does lactase do?
it has only one substrate – breaks down lactose to glucose and galactose
130
What does maltase do?
can degrade the α-1,4 linkages in straight chain oligomers up to nine monomers in length
131
What is sucrase specifically responsible for?
hydrolysing sucrose to glucose and fructose
132
What is unique about the enzyme isomaltase?
the only enzyme that can split the branching α-1,6 linkages of α-limit dextrins
133
What is the rate limiting step in assimilation of oligosaccharides?
in most it is the transport of the released monomers byt for lactose it is the rate of hydrolysis
134
Where are the final products of carbohydrate absorption - glucose galactose and fructose absorbed?
in the duodenum and jejunum
135
How are the carbohydrate monomers absorbed?
- 2 step process involving entry and exit from the enterocytes via the apical and basolateral membranes, respectively
- Glucose and galactose are absorbed by secondary active transport mediated by SGLT1; fructose by facilitated diffusion mediated by GLUT5.
- exit from the enterocytes for all monosaccharides is mediated by facilitated diffusion by GLUT2
136
What are the criteria for substrates to be transported by SGLT1?
- A hexose in the D-conformation
| - One that can form a pyranose ring
137
Where is the internal sphincter or the anus in relation to the external sphincter?
The external sphincter surrounds the internal sphincter
138
What is the function of the caecum and appendix?
no specialised function in humans
139
What is the appendix?
a blind-ended tube with extensive lymphoid tissue connected to the distal caecum via the appendiceal orifice that may be obstructed by a faecalith, potentially causing appendicitis
140
How does material reach the caecum from the terminal ileum?
Through the gastrolileal reflex in response to gastrin and CCK through 1 way ileocaecal valve
141
What s the function of the ileocacael valve?
maintaining a positive resting pressure
relaxing in response to distension of the duodenum
contracting in response to distension of the ascending colon
being under the control the vagus nerve, sympathetic nerves, enteric neurones and hormonal signals
142
What at the constituents of the large intestine?
```
Caecum and appendix
Colon
- ascending
- transverse
- descending
- sigmoid
Rectum
Anal canal and anus
```
143
What are the 3 strands of the longitudinal smooth muscle ayer in the caecum and colon?
the Taeniae coli (in the rectum and anal canal the smooth muscle encircles)
144
What are haustra?
they are sac-like bulges which very slowly move position due to the activity of the taeniae coli and the circular muscle layers in the colon
145
What are the primary functions of the colon?
```
net absorption of Na+ Cl- & H2O to condense ileocaecral material to solid stool
absorption of short chain fatty acids
secretion of K+, HCO3- and mucus
reservoir (storage)
periodic elimination of faeces
```
146
What happens to carbohydrate not absorbed in the small intestine?
it is fermented by colonic flora to short chain fatty acids
147
What is faeces made up of?
100g water
| 50g - cellulose, bacteria, bilirubin and a small amount of salt
148
Describe the mucosa of the colon
No villi but has colonic folds, crypts and microvilli to increase SA
149
What do colonocytes do?
surface epithelial cells - mediate electrolyte absorption which drives water absorption through osmosis
150
What do coloni crypt cells do
mediate ion secretion
151
What do goblet cells in the colon secrete?
copious mucus containing glycosaminoglycans – hydrated to form a slippery surface gel
trefoil proteins involved in host defence
152
What hormone increases Na+ absorption and K+ secretion
aldosterone
153
What is the effect on electrolytes of secretory diarrhoea?
significant loss of K+
154
What are the 3 patterns of motility in the large intestine?
Haustration
Peristaltic propulsive movements
Defaecation
155
What is haustration?
non-propulsive segmentation
haustra are saccules caused by alternating contraction of the circular muscle – similar to segmentation in function, but much lower frequency (minutes) – contributes to long transit time (16 – 48 hours)
disappear before and reappear after a mass movement
probably generated by slow wave activity
mixes content – allows time for fluid and electrolyte reabsorption
156
What is peristaltic propulsive movement in the large intestine?
simultaneous contraction of large sections (about 20 cm) of the circular muscle of the ascending and transverse colon, powerfully drives faeces into distal regions
- 3 times a day often triggered by a meal through the gastro colic response (gastrin and extrinsic nerve plexus)
In the distal colon this propels faeces to the rectum and triggers defaecation reflex due to rectal stretch
157
What is process of defecation?
The rectum fills with faecal matter and triggers the activation of the rectal stretch receptors
The afferents to the spinal cord are activated, then the parasympathetic efferents and then the smooth muscle of the sigmoid colon and rectum contracts while the internal anal sphincter relaxes
The process of defaecation is then determined by the external anal sphincter
158
What determines whether the external anal sphincter contracts or relaxes?
the rectal stretch receptors activate the afferents to the brain in the pelvic nerve providing the urge to defaecate the efferents to the spinal cord's firing is altered
This firing is through the pudendal nerve
If the sphincter is contracted the defaecation is delayed and the rectal wall gradually relaxes
159
What assists defaecation if the external anal sphincter relaxes?
straightening of the anorectal angle
abdomenal skeletal muscle contraction
expiration against closed glottis
160
What is the benefit of the comensal bacteria within the colon?
increase intestinal immunity by competition with pathogenic microbes
promote motility and help maintain mucosal integrity
synthesise vitamin K2 and free fatty acids (from carbohydrate) that are absorbed
activate some drugs (e.g. used in treatment of IBD)
161
Where does the gas released as flactus arise from?
swallowed air some enters small intestine but is either absorbed, or passed to the colon
bacteria in the colon which attack forms of carbohydrate that are indigestible to humans
gas that is not absorbed in the large intestine is expelled through the anus - selective expulsion requires abdominal contractions; internal and external sphincters are contracted to form an ‘exit’ too narrow for solid matter to escape
162
What is the role of the liver in carbohydrate metabolism?
hormonally regulated
gluconeogenesis – to produce glucose from amino acids
glycolysis – to form pyruvate thence lactate (anaerobic conditions), or acetyl-coA (aerobic conditions)
glycogenesis – to store polymerised glucose, as glycogen
glycogenolysis – to release glucose, as required from glycogen
163
What is the role of the liver in fat metabolism?
breakdown and synthesis of fats
processing of chylomicron remnants
synthesis of lipoproteins (e.g. VLDLs, HDLs; for export) and cholesterol (for steroid hormone and bile acid synthesis)
ketogenesis (in starvation) – important for neuronal function
164
What is the role of the liver in protein metabolism?
synthesis of plasma proteins
transamination and deamination of amino acids
conversion of ammonia to urea
165
What is the role of the liver in hormone metabolism?
It deactivates - insulin glucagon, ADH, vasopressin and steroid hormones
It converts thyroid hormone (TH) by deiodination of thyroxine (T4) to the more active triiodothyronine (T3)
It converts vitamin D to the intermediate calcifediol further activation occurs in the kidney
166
What does the liver store?
fat soluble vitamins
water soluble vitamin B12 - long term storage
iron and copper
glycogen
167
What proteins does the liver synthesise for export?
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coagulation factors II, VII, IX and X, Also proteins C and S
albumin
complement proteins
apolipoproteins
carrier proteins
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168
What is the role of the liver in protection?
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Kupffer cells (liver phagocytes) digest/destroy particulate matter and senescent (old) erythrocytes – note metabolism of haemoglobin
Production of immune factors - host defence proteins (acute phase proteins)
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169
What is the role of the liver in detoxification?
Many endogenous substances - e.g. bilirubin as a metabolite of the breakdown of haemoglobin
exogenous substances - drugs and ethanol
170
What is the function of bile?
in the digestion and absorption of fats
| the excretion of products of metabolism (including drug metabolites)
171
When is bile produced?
Continuously through the combined secretion from hepatocytes and cholangiocytes (bile ducts cells)
172
Where is bile between meals?
stored and concentrated in gall bladder (sphincter of Oddi closed)
173
Where is bile during a meal?
chyme in duodenum stimulates gall bladder smooth muscle to contract (via CCK and vagal impulses)
sphincter of Oddi opens (via CCK)
bile spurts into duodenum via cystic and common bile ducts (mixed with bile from liver)
174
Why is bile neutral/ slighly alkaline?
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to assist
micelle formation
neutralization of chyme
pH adjustment for digestive enzyme action
protection of the mucosa
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175
What does the primary bile juice made by the hepatocytes contain?
The primary bile acids mainly cholic and chenodeoxycholic acids
Water and electrolytes
Lipids and phospholipids
Cholesterol (excess cholesterol relative to bile acids and lecithin may precipitate into microcrystals that aggregate into gall stones - cholelithiasis)
IgA
Bilirubin
Metabolic wastes and conjugated drug metabolites
176
What happens to bile once it's in the ileum?
5% is lost to faeces and the rest is reabsorbed by active transport in the terminal ileum and undergoes enterohepatic recycling
177
What happens to the primary bile acids once they are secreted?
(cholic and chenodeoxycholic) are dehydroxylated by bacteria in the gut to form the secondary bile acids (deoxycholic and lithocholic), all of which are returned to the liver
there they are conjugated with glycine or taurine and recycle as bile salts
178
Examples of bile acid sequestrants (Resins)
Colveselam, colestipol, colestyramine
179
How do resins work in terms of bile?
They bind to the bile acids preventing their reabsorption
180
What are the effects of bile acid sequestrants on LDL cholesterol?
indirectly lower plasma LDL cholesterol
promote hepatic conversion of cholesterol to bile acids
increase cell surface expression of LDL-receptor in hepatocytes
increase clearance of LDL-cholesterol from plasma
181
What are the clinical uses of bile acid sequestrants?
hyperlipidaemia (limited effect)
cholestatic jaundice (itch)
bile acid diarrhoea
182
What are the limitations of bile acid sequestrants?
unpalatable, inconvenient (large dosages)
frequently cause diarrhoea
reduced absorption of fat-soluble vitamins, and some drugs (e.g. thiazide diuretics)
183
What effect does phase I metabolism have on drugs?
it makes drugs more polar and ads a chemically reactive group permitting conjugation
184
What is the effect of phase II metabolism on drugs?
it adds an endogenous compund increasing the polarity of the drug - conjugation
185
What is cytochrome P450?
Haemproteins located in the endoplasmic reticulum of the liver hepatocytes which mediate oxidation reactions
186
What is glucuronidation?
a common reaction involving the transfer of glucuronic acid to electron-rich atoms of the substrate which is part of phase II
endogenous substances are subject to glucuronidation
187
What is diarrhoea?
loss of fluid and solutes from the GI tract in excess of 500 ml per day
188
What are the principle mechanisms of fluid movement within the intestines?
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Na+/glucose co-transport
Na+/amino acid co-transport
Na+/H+ exchange
Parallel Na+/H+ and Cl-/HCO3- exchange
Epithelial Na+ channels (ENaC)
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189
What is the key solute in water absorption within the intestines?
The absorption of Na+
190
Describe Na+/glucose and Na+/amino acid cotransport?
- major postprandial Na+ absorption in the jejunum
- secondary active transport, electrogenic as is the Na+/ATPase - overall transport of Na+ generates a transepithelial potential which makes the lumen negative drives parallel Cl- absorption
191
Describe Na+/H+ exchange
in the jejunum occurs in the apical and basolateral membranes but only apical contributes to transepithelial movement of Na+
- exchange is stimulated by the alkaline environment due to the bicarbonate from the pancreas
192
Describe Na+/H+ and CI-/HCO3- exchange in parallel
in the ileum and proximal colon
primary mechanism in the interdigestive period - no postprandial absorption
- electoneutral
- regulated by intracellular cAMP, cGMP and Ca2+, all reduce NaCl absorption
- reduced NaCl absorption can cause diarrhoea
193
Describe Na+ uptake by epithelial Na+ channels (ENaC)
- mediate electrogenic Na+ absorption in the distal colon
- very efficient - important in Na+ conservation
- increased by aldosterone not regulated by cAMP or cGMP
194
What are the actions of aldosterone in relation to ENaC?
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opens ENaC (seconds)
inserts more ENaC into membrane from intracellular vesicle pool (minutes)
increases synthesis of ENaC and Na+/K+-ATPase (hours)
```
195
What causes Cl- absorption?
the -ve lumen potential due to electrogenic transport of Na+
in the small intestine - Na+/glucose and Na+/amino acid
in the large intestine - movement of Na+ through ENaC
Cl--HCO3- exchange
parallel Na+-H+ and Cl--HCO3- exchange
196
What are the mechanisms of Cl- secretion?
- from crypt cells rather than villus
- low intracellular Na+ means K+, Cl- and Na+ move into the cell, the K+ leaves via its channels but Cl- biulds up and provides an electrochemical gradient for Cl- to exit cell via CFTR on the apical membrane
197
What is the role of CFTR?
- normally the apical CFTR is closed or not present so there is little Cl-
- once there is opening of channels at the apical membrane & insertion of channels from intracellular vesicles into the membrane then there is Cl- conductance - this results in secretory diarrhoea
198
What causes indirect activation of CFTR?
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bacterial enterotoxins
hormones and neurotransmitters
immune cells products
some laxatives
secondary messengers - cAMP, cGMP, Ca2+
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199
What are the causes of diarrhoea?
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infectious agents – viruses, bacteria
chronic disease
toxins
drugs
psychological factors
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200
How do rehydration therapy sachets for diarrhoea work on SGLT1?
2 Na+ bind
Affinity for glucose increases, glucose binds
Na+ and glucose translocate from extracellular to intracellular
2 Na+ dissociate, affinity for glucose falls
Glucose dissociates
Cycle is repeated
