Physiology Flashcards
(304 cards)
1
Q
What is the term used to describe when food moves in the direction of mouth to anus?
A
Aboral
2
Q
What is the term used to describe when food moves from the anus to mouth direction?
A
Oral direction
3
Q
Name the accessory structures of the alimentary canal
A
- salivary glands
- the pancreas
- the liver and gall bladder (hepatobiliary system)
4
Q
Describe the basic function of mouth and oropharynx
A
- chops and lubricates food
- starts carbohydrate digestion
- delivers food to oesophagus
5
Q
Describe the basic function of the oesophagus
A
Propels food to stomach
6
Q
Describe the basic function of the stomach
A
- stores / churns food
- continues carbohydrate digestion
- initiates protein
- digestion
- regulates delivery of chyme to duodenum
7
Q
Describe the basic function of the small intestine
A
- duodenum, jejunum, ileum
- principal site of digestion and absorption of nutrients
8
Q
Describe the basic function of the large intestine
A
- caecum, appendix and colon
- colon reabsorbs fluids and electrolytes
- stores faecal matter before delivery to rectum
9
Q
Describe the basic function of the rectum and anus
A
Regulated expulsion of faeces
10
Q
What are sphincters?
A
Muscular constrictions
11
Q
What is chyme?
A
Small particles of food
12
Q
Name the four layers of the digestive tract wall
A
- mucosa
- submucosa
- muscularis externa
- serosa
13
Q
Describe the mucosa
A
- mucous membrane (epithelial, exocrine gland and endocrine gland cells)
- lamina propria (capillaries, enteric neurones, gut-associated lymphoid tissues)
- muscularis mucosae
14
Q
Describe the submucosa
A
- connective tissue
- larger blood and lymph vessels
- submucous plexus (neurone network)
15
Q
Describe the muscularis externa
A
- circular muscle layer
- myenteric plexus (neurone network)
- longitudinal muscle layer
16
Q
Describe the serosa
A
Connective tissue
17
Q
Name the four major functions of the digestive tract
A
- motility
- secretion
- digestion
- absorption
18
Q
Describe motility
A
Mechanical activity mostly involving smooth muscle (skeletal at mouth, pharynx, upper oesophagus and external anal sphincter)
19
Q
Describe secretion
A
Into the lumen of the digestive tract occurs from itself and accessory structure in response to the presence of food, hormonal and neural signals. Required for digestion, protection and lubrication
20
Q
Describe digestion
A
Chemical breakdown by enzymatic hydrolysis of complex foodstuffs to smaller, absorbable units
21
Q
Describe absorption
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
22
Q
What is the gastrointestinal motility mostly due to?
A
The activity of the smooth muscle
23
Q
The activity of the smooth muscle includes which muscles?
A
- circular
- longitudinal
- muscularis mucosae
- skeletal muscle is important in the mouth, pharynx, upper oesophagus and external anal spinchter
24
Q
Describe circular muscle contraction
A
Lumen becomes narrower and longer
25
Describe longitudinal muscle contraction
Intestine becomes shorter and fatter
26
Describe muscularis mucosae contraction
Change in absorptive and secretory area of mucosa (folding), mixing activity
27
Adjacent smooth muscle cells are coupled by what?
- gap junctions
| - electrical currents flow from cell to cell
28
Describe a synchronous wave
- hundreds of cells are depolarised and contract at the same time a synchronous wave
- ie. single unit smooth muscle as opposed to multiunit smooth muscle
29
Spontaneous activity across the coupled cells is driven by what?
Specialised pacemaker cells
30
Spontaneous activity across the coupled cells is modulated by what?
- intrinsic (enteric) and extrinsic (autonomic) nerves
| - numerous hormones
31
Describe slow waves
- in the stomach, small and large intestine spontaneous electrical activity occur as slow waves
- rhythmic patterns of membrane depolarisation and repolarisation that speed from cell to cell via gap junctions
32
Slow waves determine what?
Determines the frequency, direction and velocity of rhythmic contractions
33
Slow waves are driven by what cells?
- interstitial cells of cajal (ICCs)
34
What are interstitial cells of cajal?
Pacemaker cells located largely between the circular and longitudinal muscle layers
35
Describe the interstitial cells of cajal
- form gap junctions with each other and smooth muscle cells electrically coupling them
- slow waves in ICCs drive slow waves in the smooth muscle cells coupled to them
- some ICCs forma bridge between nerve endings and smooth muscle cells
36
How does contraction in the intestine occur?
Occurs only if the slow wave amplitude is sufficient to reach a threshold to trigger smooth muscle cell calcium action potentials (spikes)
37
Force is related to what?
The number of action potentials discharged (driven in turn by the duration of the slow wave that is above threshold)
38
What is the upstroke and the downstroke of the action potential due to?
- upstroke mediated by voltage- activated Ca2+ channels
| - downstroke by voltage activated K+ channels
39
What is the basic electrical rhythm also known as?
Slow waves
40
What does whether slow wave amplitude reaches the threshold depend on?
- neuronal stimuli
- hormonal stimuli
- mechanical stimuli
Generally act to depolarise smooth muscle cells rather than influence slow waves directly, depolarisation shifts slow wave peak to threshold
41
Describe the parasympathetic innervation of the GI tract
Preganglionic fibres (releasing ACh) synapse with ganglion cells (in essence post-ganglionic neurones) within the enteric nervous system (ENS)
42
Describe the excitatory influences of the parasympathetic innervation of the GI tract
- increased gastric, pancreatic and small intestinal secretion
- blood flow
- smooth muscle contraction
43
Describe the inhibitory influences of the parasympathetic innervation of the GI tract
Relaxation of some sphincters, receptive relaxation of the stomach
44
Describe the sympathetic innervation of the GI tract
Preganglionic fibres (releasing ACh) synapse in the prevertebral ganglia. Postganglionic fibres (releasing NA) innervate mainly enteric neurones, but also other structures
45
Describe the excitatory influences of the sympathetic innervation of the GI tract
Increased sphincter tone
46
Describe the inhibitory influences of the sympathetic innervation of the GI tract
Decreased motility, secretion and blood flow
47
The enteric nervous system neurones are mostly located in ganglia connected by fibre tracts within what?
- myenteric (auerbachs) plexus
| - submucous (meissners) plexus
48
Describe the main role of the myenteric plexus
Mainly regulates motility and blood vessels
49
Describe the main role of the submucous plexus
Mainly modulates epithelia and blood vessels
50
The enteric nervous system coordinates muscular, secretive and absorptive activities via what?
- sensory neurones; mechanoreceptors, chemoreceptors, thermoreceptors
- interneurons; the majority, co-ordinating reflexes and motor programmes
- effector neurones; excitatory and inhibitory motor neurones supplying both smooth muscle layers, secretory epithelium, endocrine cells and blood vessels
51
Motor and secretory activity are controlled by what?
Nerve reflexes
52
Name an example of a local reflex
Peristalsis
53
Name an example of a short reflex
Intestino-intestinal inhibitory reflex
54
What is the intestino-intrstine reflex?
Local distension activates sensory neurones exciting sympathetic pre-ganglionic fibres that cause inhibition of muscle activity in adjacent areas
55
Name an example of a long reflex
Gastroileal reflex (a vasovagal reflex)
56
Describe the gastroileal reflex
Increase in gastric activity causes increased propulsive activity in the terminal ileum
57
Describe peristalsis
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
58
Describe the altered activity of motorneurones in the propulsive segment of peristalsis
- circular muscle contracts (release of ACh and substance P from excitatory motoneurone)
- longitudinal muscle relaxes (release of VIP and NO from inhibitory motoneurone)
59
Describe the altered activity of motoneurones in the receiving segment during peristalsis
- longitudinal muscle contracts (release of ACh and substance P from excitatory motoneurone)
- circular muscle relaxes (release of VIP and NO from inhibitory motoneurone)
60
Describe segmentation
- mixing or churning movements
- rhythmic contractions of the circular muscle layer that mix and divide luminal contents
- occurs in the small intestine (in the fed state) and in the large intestine (where it is called haustration)
61
Describe colonic mass movement
Powerful sweeping contraction that forces faeces into the rectum, occurs a few times a day
62
Describe the migrating motor complex (MMC)
Powerful sweeping contraction from stomach to terminal ileum
63
Describe tonic contractions
- sustained contractions
- low pressure; organs with a major storage function (eg. stomach)
- high pressure; sphincters
64
How many sphincters of the GI tract are there (excluding the sphincter of oddi) ?
6
65
Describe sphincters
- composed of specialised circular, generally smooth muscle
- act as essentially one way valves by maintaining a positive resting pressure relative to two adjacent structures (eg. oesophagus and stomach)
- in general, stimuli (pressure) proximal and distal to a sphincter cause opening and closing respectively
66
Describe the upper oesophageal sphincter
- skeletal muscle
- relaxes to allow swallowing
- closes during inspiration
67
Describe the lower oesophageal sphincter
- relaxes to permit entry of food to the stomach
| - closes to prevent reflux of gastric contents to the oesophagus
68
Describe the pyloric sphincter
- regulates gastric emptying
| - usually prevents duodenal gastric reflux
69
Describe the ileocaecal valve
- regulated flow from ileum to caecum
| - distension of ileum opens, distension of proximal colon closes
70
Describe the internal and external anal sphincters
- internal = smooth muscle
- external = skeletal muscle
- are regulated by the defaecation reflex
71
What is energy homeostasis?
Physiological process whereby energy intake is matched to energy expenditure over time
- promotes body fuel stability- energy primarily stored as fat
72
What is not a single disorder but a heterogeneous group of conditions with multiple causes?
Obesity
73
Name the major influencing factors of obesity
- genetics
| - environment
74
What is the energy balance disturbance?
Difference between energy intake and expenditure
75
Name some consequences of obesity
- stroke (hypertension)
- respiratory disease (sleep apnoea)
- heart disease (lipids, diabetes, hypertension)
- gallbladder disease
- osteoarthritis
- dementia (alzheimers)
- NAFLD (fatty liver)
- diabetes
- cancer (uterus, breast, prostate, colon)
- hyperuricemia, gout
76
Why is fat needed?
- energy storage
- prevention of starvation
- energy buffer during prolonged illness
77
Name a survival adaptation for starvation and infection
Adipose tissue accumulation
78
The CNS influences energy balance and body weight by?
- behaviour; feeding and physical activity
- ANS activity; regulates energy expenditure
- neuroendocrine system; secretion of hormones
79
The site of integration is where?
The brain
80
The neural centre responsible is what?
Hypothalamus
eg. lesioning ventromedial hypothalamus causes obesity, lesioning lateral hypothalamus causes leanness
81
Name the three basic concepts that underlie the control of energy intake and body weight system
- satiety signalling
- adiposity negative feedback signalling
- food reward
82
What is satiation?
Sensation of fullness generated during a meal
83
What is satiety?
Period of time between termination of one meal and the initiation of the next
84
What is adiposity?
The state of being obese
85
What regulate meal initiation, termination and inter-meal frequency?
Short-term processes
86
When do satiation signals increase?
During meal to limit meal size
87
Name the five satiation signals
- cholecystokinin (CCK)
- peptide YY (PYY 3-36)
- glucagon like peptide 1 (GLP-1)
- oxyntomodulin (OXM)
- obestatin
88
Describe cholecystokinin (CCK)
Secreted from enteroendocrine cells in duodenum and jejunum. Released in proportion to lipids and proteins in meals. Signals via sensory nerves to hindbrain and stimulates hindbrain directly (nucleus of solitary tract (NTS))
89
Describe peptide YY (PYY3-36)
Secreted from endocrine mucosal L-cells of GI tract. Levels increase rapidly post-prandially. Inhibits gastric motility, slows emptying and reduces food intake (hypo)
90
Describe glucagon-like peptide 1 (GLP-1)
Product of pro-glucagon gene. Also released from L cells in response to food ingestion. Inhibits gastric emptying and reduces food intake (hypo, NTS)
91
Describe oxyntomodulin (OXM)
Also from pro-glucagon gene and released from oxyntic cells and L-cells of small intestine after meal. Acts to supress appetite - mechanism and site unclear
92
Describe obestatin
Peptide produced from gene that encodes ghrelin and released from cells lining stomach / small intestine. Suggested to reduce food intake - may act to antagonise the actions of ghrelin - actions unclear
93
What is the hunger signal?
Grehlin
94
Describe ghrelin
- octanoylated peptide, produced and secreted by oxyntic cells in stomach
- ghrelin levels increase before meals and decrease after meals
- levels are raised by fasting and hypoglycaemia
95
What does ghrelin stimulate?
Stimulates food intake, decreases energy expenditure and decreases fat utilisation - increases body weight
96
Overall energy balance is controlled by what?
Feedback loops which act to maintain constancy of total body energy stores
97
Which two hormones, produced in peripheral tissues act on hypothalamic neurons?
Adiposity signals
98
What is the effect of glutamate, gaba and opioids when injected into hypothalamic centres?
Increase food intake - effect modest / short lasting
99
Which two hormones report fat status to the brain?
Leptin and insulin
100
Where is leptin made and released from?
Fat cells
101
Where is insulin made and released from?
Pancreatic beta cells
102
Describe leptin
- member of the cytokine family
- made and secreted from adipocytes
- circulates in proportion to body adiposity
- specific transport system for leptin to enter brain
- high levels of leptin receptors in hypothalamus
103
What type of hormone is leptin?
A pleiotropic hormone
104
Describe the biological roles of leptin
- food intake / energy expenditure / fat deposition
- peripheral glucose homeostasis / insulin sensitivity
- maintenance of immune system
- maintenance of reproductive system
- angiogenesis
- tumourigenesis
- bone formation
105
What would result in leptin resistance and why?
- diet-induced obesity
- defective leptin transport into brain
- altered signal transduction following leptin binding to its receptor
106
What is the starting point for digestion of proteins?
The stomach by pepsin and HCL, continues carbohydrate digestion (by salivary amylase)
107
Describe the stomach
J shaoed bag, 50>1000ml capacity, orad region relaxes receptively (driven by vagus) to accommodate food from oesophagus
108
The stomach mixes food with what to produce chime?
Gastric secretions to produce semi-liquid chyme
109
What does the stomach secrete?
Approx. 2 litres/day of gastric juice from gastric glands in the gastric mucosa
110
Describe the mechanical activity of the stomach
- occurs as two types
- orad stomach (fundus and proximal body) - tonic ie. maintained
- caudad stomach (distal body and antrum) - phasic ie. intermittent
111
Describe the orad region of the stomach
- relaxation driven by vagus occurs during a swallow
- no slow wave activity
- tonic contractions, when they occur, are weak due to relatively thin musculature
- contents propelled intermittently to caudad region by low amplitude tonic contractions of about 1 min duration - decrease stomach size as it empties
112
What allows for carbohydrate partial digestion by salivary amylase in the stomach?
Minimal mixing of contents for long 1hr periods
113
Which hormone decreases contractions and hence rate of stomach emptying?
Gastrin
114
Describe the caudad region
- slow waves occur continuously but only those reaching threshold elicit contraction
- phasic peristaltic contractions driven by suprethreshold slow waves progress from midstomach to gastroduodenal junction (the antral wave or pump) propelling contents towards pylorus through which a very small volume of chime flows into the duodenum
- velocity of contraction increases towards the junction, overtaking the movement of chime that rebounds against constricted distal antrum back into the relaxed body of the stomach - this is retropulsion
115
What does retropulsion do?
Mixes gastric contents reducing chime (grinding function) to small particle that pass through the pylorus
116
What empties the stomach?
The antral pump
117
What determine escape of chime through the pyloric sphincter?
The strength of antral wave, or pump, determines escape
governed by; gastric factors and duodenal factors
118
Describe gastric factors of control of stomach emptying
- rate of emptying proportional to volume of chime in stomach -
- distension increases motility due to; stretch of smooth muscle, stimulation of intrinsic nerve plexuses, increased vagus nerve activity and gastrin release
- consistency of chime; emptying facilitated by thin liquid chyme
119
How does the duodenum delay emptying?
- neuronal response; the enterogastric reflex, decreases antral activity by signals from intrinsic nerve plexuses and the ANS
- hormonal response;' release of enterogastrones (eg CCK) from duodenum inhibits stomach contraction
120
Name stimuli within the duodenum that drives the neuronal and hormone responses
- FAT; particularly potent, delay in gastric emptying required for digestion and absorption in small intestine
- ACID; time is required for neutralisation of gastric acid by bicarbonate secreted from the pancreas - important for optimal function of pancreatic digestive enzymes
- HYPERTONICITY; products of carbohydrate and protein digestion are osmotically active and draw water into the small intestine - danger of reduced plasma volume and circulatory disturbance (eg. dumping syndrome)
- distension
121
The oxyntic gland area is where?
Proximal stomach including the fundus and body
122
Where is the pyloric gland area?
Distal stomach, designated the antrum
123
The gastric mucosa is composed of what?
- a surface lining the stomach
- pits, invaginations of the surface
- glands, at the base of the pits responsible for several secretions
124
Describe HCl
- activates pepsinogen to pepsin
- denatures protein
- kills most (not all) micro-organisms ingested with food
125
Describe pepsinogen
- inactive precursor of the peptidase, pepsin
| - not pepsin once formed activated pepsinogen (autocatalytic)
126
Describe intrinsic factor and gastroferrin
- bind vitamin B12 and Fe2+ respectively, facilitating subsequent absorption
127
Describe histamine
Stimulated HCl secretion
128
Describe mucus
Protective
129
Describe gastrin
Stimulated HCl secretion
130
Describe somatostatin
Inhibits HCl secretion
131
What does the gastric parietal cell secrete?
HCl
132
Name the three important secretagogues that induce acid secretion from the parietal cells
- ACh
- gastrin
- histamine
133
Describe the direct pathway of HCL secretion
In the direct pathway, ACh, gastrin and histamine stimulate the parietal cell, triggering the secretion of H+ into the lumen
134
Describe the indirect pathway of HCl secretion
In the indirect pathway, ACh and gastrin also stimulate the ECL cell, resulting in secretion of histamine. This histamine then acts on the parietal cell
135
Stimuli for secretion of H+ act by what?
Both PLC - IP3 (gastrin ACh) and cAMP - PKA (histamine) signalling pathways
136
Stimuli for inhibition of secretion of H+ act by what?
cAMP-PKA (somatostatin, prostaglandins) signalling pathways
137
What molecules stimulate and inhibit adenylate cyclase?
- histamine stimulates
| - somatostatin and prostaglandins inhibit
138
Secretagogues cause what?
Trafficking of the H+/K+ATPase
139
Describe the resting state of the parietal cell
H+/K+ATPase is largely within cytoplasmic tubulovesicles
140
Describe the stimulate state of the parietal cell
H+/K+ATPase traffics to the apical membrane taking residence in extended microvilli
141
Rate of gastric secretion is controlled by what?
Stimulatory and inhibitory mechanisms that occur in three overlapping phases
142
Name the three phases of gastric acid secretion
- cephalic phase
- gastric phase
- intestinal phase
143
Describe the cephalic phase of gastric acid secretion
- in the head
- before food reaches the stomach preparing the stomach to receive food
- driven directly and indirectly by the CNS and vagus nerves (CNX)
144
Describe the gastric phase of gastric acid secretion
- when food is in the stomach
| - involves both physical and chemical mechanisms
145
Describe the intestinal phase of gastric acid secretion
- after food has left the stomach
- chyme entering the upper small intestine causes weak stimulation of gastric secretion via neuronal and hormonal mechanisms
146
The vagus stimulates enteric neurones that do what during the cephalic phase?
- release ACh directly activating parietal cells (neurotransmitter action)
- via release of GRP causes release of gastrin from G cell into systemic circulation that activates parietal cells (endrocrine 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
147
Describe the cephalic phase in relation to inhibition of gastric acid secretion
- vagal nerve activity decrease upon cessation of eating and following stomach emptying
148
Describe the gastric phase in relation to inhibition of gastric acid secretion
- 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
149
Describe the intestinal phase in relation to inhibition of gastric acid secretion
The factors that reduce gastric motility also reduce gastric secretion (eg. neuronal reflexes, enterogastrones)
150
The small intestine receives what?
- chyme from stomach (via the pylori sphincter)
- pancreatic juice from the pancreas
- bile from liver and gall bladder (both via the sphincter of oddi)
151
The small intestine secretes what?
Intestinal juice (succus entericus)
152
Motility of the small intestine causes what?
- 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)
153
How is the small intestine well adapted for absorption?
- circular folds (of kerckring)
- villi
- microvilli (brush border)
154
Name the two steps involved in the mixing and propulsion of chyme in the small intestine
- segmentation (mixing) in the digestive state
| - peristalsis in the interdigestive or fasting state
155
Describe segmentation (mixing) in the digestive state
- chopping moves chyme back and forth, very vigorour after a meal, little or none between meals
- alternating contraction and relaxation of segments of circular muscle
- initiated by small intestine pacemaker cells causing the BER which is continuous, at threshold activates segmentation which in the duodenum is primarily due to distension by entering chyme
- duodenum has frequent segmentation contractions, ileum has fewer, net movement is slightly aboral
- movement is slow
- strength of segmentation enhanced and decreased by parasympathetic and sympathetic activity, respectively
- segmentation in the empty ileum is triggered by gastrin from the stomach (gastroileal reflex)
156
Describe peristalsis in the interdigestive or fasting state
- a few localise contractions
- the migrating motor complex
- note macrolide antibiotic eg. erythromycin mimic effect of motilin and may cause GI disturbances
157
Describe the migrating motor complex (MMC)
- occur between meals every 90-120 minutes
- strong peristaltic contraction slowly passing length of the intestine (stomach > ileocaecal valve)
- clears small intestine of debris, mucus and sloughed epithelial cells between meals ; housekeeper function
- inhibited by feeding and vagal activity
- triggered by motilin, supressed by gastrin and CCK
158
Which peptide hormones does the small intestine secrete into the blood?
- gastrin
- secretin
- cholecystokinin CCK
- glucose dependent insulinotropic peptide
- glucagon like peptide 1
- motilin
- ghrelin
159
Describe glucose-dependent insulinotropic peptide
- from K cells of duodenum and jejunum
- released in response to glucose, amino acid and fatty acids
- stimulates release of insulin from pancreatic beta cells (incretin action)
- inhibits gastric emptying
160
Describe glucagon like peptide 1
- from L cells of the small intestine
- stimulates insulin secretion
- inhibits glucagon secretion from pancreatic alpha cells
- decreases gastric emptying and appetite
161
Describe motilin
- from M cells of duodenum and jejunum, secreted during fastin state
- initiates the migrating motor complex
162
All peptide hormones act on what?
G protein coupled receptors
163
Incretins act upon what?
Beta cells of the pancreas in essentially feed-forward manner to stimulate the release of insulin
164
Describe the control mechanisms of succus entericus secretion
- distension / irritation
- gastrin
- CCK
- secretin
- parasympathetic nerve activity
^^ all enhance
- sympathetic nerve activity decreases
165
Succus entericus secretion lacks digestive enzymes but contains what?
- mucus; for lubrication / protection (from goblet cells)
| - aqueous salt; for enzymatic digestion (mostly from the crypts of lieberkuhn)
166
Name the endocrine secretions from the pancreas
Insulin and glucagon - secreted to blood
167
Name the exocrine secretion from the pancreas
Digestive enzymes (acinar cells), aqueous NaHCO3- solution (duct cells0) - secreted to the duodenum collectively as pancreatic juice
168
Describe secretion of the pancreatic duct cells
- secrete 1-2 litres of alkaline (HCO3- rich) fluid into the duodenum per day
- neutralised acidic chyme for entering the duodenum; provides optimum pH for pancreatic enzyme function, protects the mucosa from erosion by acid
169
Which enzymes can completely digest food in the absence of all other enzymes?
Pancreatic enzymes
170
Define digestion
The enzymatic conversion of complex dietary substances to a form that can be absorbed
171
Luminal digestion is mediated by what?
Mediated by enzymes secreted into the duodenum
172
Membrane digestion is mediated by what?
Enzymes at the brush border of epithelial cells
173
Define absorption
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)
174
What is assimilation?
The overall process of digestion and absorption
175
What provides 45% of total energy requirements?
Digestible carbohydrate
176
All dietary carbohydrate must be converted to what for absorption?
Monosaccharides
177
Describe the role of endoenzyme
- breaks down linear internal alpha 1, 4 linkages but not terminal alpha 1,4 linkages - hence no production of glucose
- cannot cleave alpha 1,6 linkages at branch points (in amylopectin) or alpha 1,4 linkages adjacent to branch points
- products are thus linear glucose oligomers (maltotriose, maltose) and alpha limit dextrins
178
Name the integral membrane proteins with a catalytic domain that faces the lumen of the GI tract
Oligosaccharidases
179
Lactase has how many substrates?
Only one - breaks down lactose to glucose and galactose
180
Describe maltase
Can degrade the alpha 1,4 linkages in straight chain oligomers up to nine monomers in length
181
Describe sucrase
Specifically responsible for hydrolysing sucrose to glucose and fructose
182
Describe isomaltase
Is unique in that it is the only enzyme that can split the branching alpha 1,6 linkages of alpha limit dextrins
183
Describe absorption of the final products of carbohydrate digestion (glucose, galactose and fructose)
- occurs in the duodenum and jejunum
- is a two step process involving entry and exit from 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 GLUT 5
- exit for all monosaccharides is mediated by facilitated diffusion by GLUT 2
184
For transport via SGLT1 the substrate must be what?
- a hexose in the beta conformation
| - one that can form a pyranose ring
185
Describe the mode of operation of SGLT1
- 2 NA+ binds
- affinity for glucose increases, glucose binds
- NA+ and glucose translocate from extracellular to intracellular
- 2 Na+ dissociate, affinity for glucose fall - glucose dissociates
- cycle is repeated
186
Protein, after the first 6 months of life, must be digested to what?
To oligopeptides and amino acids for efficient absorption
187
How many major pathways exist for protein digestion?
Four
188
What accounts for 10-15% of daily energy intake?
Protein assimilation
189
Where are additional proteases present?
- at the brush border
| - within the cytoplasm of the enterocyte
190
Brush border peptidases are?
- numerous because each enzyme attacks a limited number of peptide bonds and the oligopeptides to be digested are extremely varied in their structure
- have affinity for larger oligopeptides
- either endopeptides or exopeptides
- the latter comprising both aminopeptidases and carboxypeptidases
191
Describe cytoplasmic peptidases
- are less numerous than brush border peptidases
| - primarily hydrolyse dipeptides, or tripeptides
192
Describe amino acids in relation to protein absorption
- brush border; at least 7 different mechanisms are present
- 5 are Na+ dependent co transporters mediating uphill movement (secondary active transport)
- 2 are Na+ independent
193
Dysfunction in the 2 Na+ independent reactions can lead to what?
Cystinuria
194
Dysfunction in the 5 Na+ dependent reactions can lead to what?
Hartnup disease
195
Describe the basolateral membrane in relation to amino acids
- at least 5 different mechanisms
- 3 mediate efflux of amino acids and are Na+ independent
- 2 mediate influx and are Na+ dependent (supplying the enterocytes nutritional requirements along with absorbed amino acids)
- net movement is thus bidirectional
196
Describe di, tri and tetra-peptides transport
- via H+ dependent mechanism (pepT1, SLC15A) at brush border (co-transport)
- further hydrolysed to amino acids within the enterocyte
- Na+ independent systems at the basolateral membrane (facilitated transport)
197
Ingested lipids comprise of what?
- fats/oils; triacylglycerols. Fatty acids may be saturated, unsaturated, ratio is high in animal fats and low in plant
- phospholipids; mostly glycerophospholipids eg. lecithin
- cholesterol and cholesterol esters
- fatty acids
198
Emulsification of ingested lipids occurs by what?
- mouth; chewing
- stomach; gastric churning and squirting through the narrow pylorus, context mixed with digestive enzymes from mouth and stomach
- small intestine; segmentation and peristalsis mix the luminal content with pancreatic and biliary secretions
199
How are emulsion droplets stabilised?
- by the addition of a coat of amphiphilic molecules that form a surface layer on the droplets that includes;
- certain products of lipid digestion itself (eg. fatty acids, monoacylglycerols)
- biliary phospholipids
- cholesterol
- bile salts (when the droplets have progressively been reduced to unilamellar and mixed micelles)
200
Droplets produced by mechanical disruption provide what?
Provide a vast increase in the surface area to volume ratio that increases the area of the oil water interface at which digestion by lipases and other esterases can accomplish digestion
201
Lipid digestion of TAG by lipases proceeds as
- mouth; lingual phase
- stomach; gastric phase by gastric lipase (and lingual lipase in saliva)
- gastric lipase secreted in response to gastrin from chief cells
202
Describe gastric lipase
- has a pH optimum of 4 and is resistant to pepsin
- is inactive in the duodenum due to digestion by pancreatic protease and unfavourable pH
- preferentially hydrolyses TAGs at the 3 position
203
Which chain fatty acids are absorbed into the stomach and which ones are not?
- short and medium chain fatty acids are absorbed
| - long chain fatty acids are not
204
What does diacylglycerol + free fatty acids do?
Stimulates CCK release from duodenum and secretion of pancreatic lipase
205
Digestion by pancreatic lipase produces what?
2-monoacylglycerol and free fatty acids
206
Pancreatic lipase is secreted from where?
- acinar cells of pancreas in response to CCK which also stimulates bile flow
207
Full activity of pancreatic lipase
- colipase co-factor
- alkaline pH
- Ca2+
- bile salts
- fatty acids
208
Pancreatic lipase mainly hydrolyses TAGs where?
At the 1 and 3 positions
209
Describe the role of bile salt
- bile salts released into the duodenum in bile from the gall bladder in response to CCK act as detergents to help emulsify large lipid droplets to small droplets
- bile salts are amphipathic
- increase surface area for attack by pancreatic lipase but blocks access of the enzyme to the TAGs
210
Failure to secrete bile salts results in what?
- lipid malabsorption- steatorrhoea (fat in faeces)
| - secondary vitamin deficiency due to failure to absorb fat soluble vitamins (A,D,E and K)
211
Describe colipase
- an amphipathic molecule
- secreted with lipase by the pancreas
- binds to bile salts and lipase allowing access by the latter to tri and di-acylglycerols
- colipase is secreted as inactive procolipase which is activated by trypsin
212
Where are the final products of lipid digestion stored in are released from?
Mixed micelles
213
What happens as TAGs towards the surface of the emulsion droplets are hydrolysed?
They are replaced by TAGs within the core, decreasing droplet size until a mixed micelle results
214
Short chain and medium fatty acids diffuse through where?
- the enterocyte
| - exit through the basolateral membrane and enter the villus capillaries
215
Long chain fatty acids and monoglycerides are re-synthesised to what?
Triglycerides in the endoplasmic reticulum and are subsequently incorporated into chylomicrons
216
Describe the absorption of Ca2+
- occurs by passive (ie. paracellular, the whole length of small intestine) and active (ie. transcellular, mainly duodenum and upper jejunum) transport mechanisms
- with Ca2+ in chyme absorption is mainly active
- active Ca2+ absorption is regulated by 1,25 dihydroxyvitamin D3 (calcitrol) and parathyroid hormone
217
Describe iron
- one of the most abundant elements on earth
- an important constituent of haemoglobin and myoglobin and acts as co-factor for numerous enzyme-mediated processes
- crucially important in carriage of oxygen by haemoglobin
- daily loss of iron from the body (via urine, sweat and desquamated enterocytes) is an unregulated process
- iron balance within the body, long term, depends upon tightly regulated absorption of iron across the duodenum which matches losses
218
Describe dietary iron
- mainly in the oxidised form, Fe3+, present in meat or vegetables as inorganic iron, haem or ferratin
- required in only minor amounts daily
219
Describe absorption of iron
- a complex and tightly regulated process contributing to a balances level of the element in the body
- Fe2+ absorbed across the apical membrane by transport processes
- Fe2+ conveyed to basolateral membrane via a molecular chaperone
- Fe2+ transported across the basolateral membrane by transport process
- Fe2+ oxidised yo Fe3+ and then transported to tissues
- import of haem across apical membrane followed by cytoplasmic metabolism to release Fe2+
220
What does iron deficiency cause?
- microcytic anaemia
221
What dose excess iron cause?
- excess is toxic due to accumulation in liver pancreas and heat
- molecularly the production of hydroxyl radicals and hydroxide ions
222
Describe the absorption of vitamin B12
- ingested in food bound to proteins
- stomach acid releases vitamin B12 from protein
- haptocorin, secreted in saliva binds vitamin B12 released in stomach
- stomach parietal cells release intrinsic factor
- pancreatic proteases digest haptocorin in small intestine, vitamin B12 released
- vitamin B12 binds to intrinsic factor in small intestine
- vitamin B12 intrinsic factor complex absorbed in terminal ileum by endocytosis
223
Describe absorption of fat soluble vitamins
- A,D,E and K
- absorption requires adequate bile secretion and an intact intestinal mucosa
- incorporated into mixed micelles
- usually passively transported into enterocytes
- incorporated into chylomicrons or VLDLs
- distributed by intestinal lymphatics
224
Describe the metabolic functions of the liver
- regulation of carbohydrate, lipid and amino acid metabolism
225
Describe carbohydrate metabolism in the liver
- hormonally regulated
- gluconeogenesis; to produce glucose from amino acids
- glycolysis; to form pyruvate then lactate(anaerobic), or acetyl-coA (aerobic)
- glyconeogenesis; to store polymerised glucose as glycogen
- glycogenolysis; to release glucose as required
226
Describe fat metabolism in the liver
- breakdown and synthesis
- processing of chylomicron remnants
- synthesis of lipoproteins (eg. VLDLs, HDLs for export) and cholesterol (for steroid hormone and bile acid synthesis)
- ketogenesis (in starvation) important for neuronal function
227
Describe protein metabolism in the liver
- synthesis of plasma proteins
- transamination and deamination of amino acids
- conversion of ammonia to urea
228
Which hormones are deactivation in the liver?
- insulin
- glucagon
- anti-diuretic hormone (ADH, vasopressin)
- steroid hormones
229
Which hormones are activated in the liver?
- conversion of thyroid hormone (by deiodination of thyroxine T4, to the more reactive triiodothyronine T3)
- conversion of vitamin D to 25-hydroxyvitamin D2 (calcifediol), further activation to 1,25 dihydroxyvitamin D3 (calcitrol) occurs in the kidney
230
What are the categories of major function of the liver?
- storage of
- synthesis of proteins
- protection
- detoxification
231
Describe the storage function of the liver
Storage of;
- fat soluble vitamin
- water soluble vitamin B12
- iron, copper
- glycogen
232
Describe the synthesis of proteins in the liver
- for the metabolic processes of the organ
- for export
- coagulation factors 2,7,8, 10 also proteins C and S
- albumin
- complement proteins
- apolipoproteins
- carrier proteins
233
Describe the protection function of the liver
- Kupffer cells (liver phagocytes) digest/destroy particulate matter eg. bacteria and senescent (old) erythrocytes
- production of immune factors, host defence proteins (acute phase proteins)
234
Describe the detoxification function of the liver
- many endogenous substances (eg. bilirubin as a metabolite of haemoglobin breakdown)
- exogenous substances (xenobiotics), drugs, ethanol (alcohol)
235
Describe the secretion of bile
- participates in the digestion and absorption of fats and the excretion of products of metabolism (including drug metabolites)
- produced continuously (0.6-1.2 litres per day by combined secretion from hepatocytes and bile duct cells)
236
Describe the secretion of bile between meals
- stored and concentrated in gall bladder (sphincter of oddi closed)
237
Describe secretion of bile during a meal
- chime in duodenum stimulates gallbladder 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)
238
Neutral / slightly alkaline bile assists what?
- micelle formation
- neutralisation of chyme
- pH adjustment for digestive enzyme action
- protection of the mucosa
239
What is secreted from hepatocytes?
- primary bile acids, mainly cholic and chenodeoxycholic acids
- water and electrolytes including Na+, K+, Ca2+, Cl- and HCO3-
- lipids and phospholipids eg. lecithin
- cholesterol
- IgA
- bilirubin
- metabolic wastes and conjugated drug metabolites
240
Describe bilirubin
- breakdown product of the porphyrin component of haemoglobin
- pigment rendering urine yellow and faeces brown
- when present in excess causes jaundice
241
What is the most common pathology of the biliary tract?
Cholelithiasis
242
How do gall stones form?
Concentration of bile in the gall bladder (caused by reabsorption of water) produces a supersaturated solution that is unstable. Cholesterol may crystallise and over time grow into a gall stone
243
What is the best treatment for symptomatic stones (eg. causing cholangitis or pancreatitis)
Laproscopic cholecystectomy
244
When would ursodeoxycholic acid be suitable for patients?
May be suitable for patients with unimpaired gall bladder function who have small / medium sized radiolucent stones (CH stones) which it dissolves. Diarrhoea is an adverse effect
245
Why may morphine make colic pain worse?
May worsen pain dut to constriction of the sphincter of oddi and increased intrabiliary pressure. Alternatives are buprenorphine and pethidine
246
Biliary spasm can be relieved by what?
Atropine or GTN
247
What is enterohepatic recycling?
only a small fraction of bile salts entering the duodenum is lost in the faeces, most is reabsorbed by active transport in the terminal ileum and undergoes enterohepatic recycling
248
Loss of bile acid is matched by what?
Synthesis requiring utilisation of hepatic cholesterol
249
A fraction of the primary bile acids (cholic and chenodeoxycholic) are dehydroxylated by what?
By bacteria in the gut to form the secondary bile acids (deoxycholic and lithocholic) all of which are returned to the liver
250
What happens to secondary bile acids upon returning to the liver?
They are conjugated with glycine or taurine and recycle as bile salts (of Na+ and K+)
251
Name some examples of bile acid sequestrants (resins)
- colveselam
- colestipol
- colestyramine
252
Describe the function of bile acid sequestrants (resins)
- neither digester nor absorbed by the gut
- act by binding to bile acids, preventing their reabsorption
- lower plasms LDL cholesterol indirectly
253
Describe how bile acid sequestrants (resins) lower plasma LDL cholesterol indirectly
- promote hepatic conversion of cholesterol to bile acids
- increase cell surface expression of LDL receptor in hepatocytes
- increase clearance of LDL-cholesterol from plasma
254
Describe the clinical uses of bile acid sequestrants (resins)
- hyperlipidaemia (limited effect)
- cholestatic jaundice (itch)
- bile acid diarrhoea
255
Describe the limitations and adverse effects of bile acid sequestrants (resins)
- unpalatable, inconvenient (large doses)
- frequently cause diarrhoea
- reduced absorption of fat-soluble vitamins and some drugs (thiazide diuretics)
256
Drugs are xenobiotics - drug metabolism acts to?
- covert parent drugs to more polar metabolites that are not readily reabsorbed by the kidney (from the renal tubes), facilitating excretion
- convert drugs to metabolites that are usually pharmacologically less active than the parent compound
257
Describe phase 1 of drug metabolism
- oxidation
- reduction
- hydrolysis
- makes drug more polar, adds a chemically reactive group (a handle) permitting conjugation (functionalisation)
258
Describe phase 2 of drug metabolism
- conjugation
- adds an endogenous compound increasing polarity
- eg. with glucuronyl, sulphate, methyl, acetyl, glycyl or glutathione groups
259
Which haem proteins located in the endoplasmic reticulum of liver hepatocytes mediates oxidation reactions (
phase 1) of many lipid soluble drugs?
The cytochrome P450 family of monooxygenases
260
Name the main gene families of cytochrome P450 in human liver
- CYP1
- CYP2
- CYP3
261
Describe phase 2 reactions
- usually result in inactive products
- largely occurs in the liver
- involves conjugation of chemically reactive groups eg. hydroxyl, thiol or amino with glucoronyl, sulphate, methyl or acetyl groups
262
Describe glucouronidation
A common reaction involving the transfer of glucuronic acid to electron-rich atoms of the substrate (N,O or S) forming an amide, ester or thiol bonds
263
Many endogenous substances are subject to what?
To glucouronidation (eg. bilirubin, adrenal corticosteroids)
264
What can happen in severe hepatic failure? eg. fulminant liver failure
- detoxification of ammonia (NH3) via the urea cycle to urea (excreted by kidneys) fails
- blood NH3 levels rise (hyperammonemia) exerting a toxic effect upon the CNS that causes incoordination, drowsiness, coma and ultimately death due to cerebral oedema
265
What is a therapeutic option for hepatic encephalopathy
- lactulose
- antibiotics (neomycin, rfiamixin) that are minimally absorbed, supress colonic flora and thus inhibit ammonia generation
266
Describe lactulose
- a semi-synthetic disaccharide of fructose and lactose which;
- is not digested or absorbed in the small intestine
- when broken down in the colon acidifies the stool (reduces pH)
- converts ammonia to ammonium which is not absorbed
267
Absorption of water is a what process driven by what?
- a passive process
| - driven by the transport of solutes (particularly Na+) form the lumen of the intestine to the bloodstream
268
Water ingested and secreted is usually in balance with what?
With water absorbed
269
What are the typical values of water absorption in the body?
- 9.3 litres entering tract per day
- 8.3 litres absorbed by small intestine
- 1 litre enters large intestine of which 90% is absorbed
270
Faeces usually contain how much water and cellulose, bilirubin and bacteria?
- around 100ml water
| - 50ml cellulose, bilirubin and bacteria
271
Define diarrhoea
A loss of fluid and solutes from the GI tract in excess of 500ml per day
272
Absorption of water in the GI tract is largely driven by what?
Reabsorption of Na+
273
Intestinal fluid movement is always couple to what?
Solute movement
274
Water may move via which routes?
Transcellular or paracellular routes
275
Reabsorption of Na+ provides what?
A local osmotic force for reabsorption of water
276
Describe the principal mechanisms of reabsorption of Na+
- Na+/glucose co-transport
- Na+ / amino acid co-transport
- Na+ / H+ exchange
- parallel Na+ /H+ and Cl- / HCO3- exchange
- epithelial Na+ channels (ENAC)
277
Where does Na+/ glucose co-transport and Na+/ amino acid co-transport take place?
- occurs throughout the small intestine and is most important in the postprandial period (also occurs in the colon in new born)
278
Where does Na+ /H+ exchange take place?
Occurs in the duodenum and jejunum and is stimulated by luminal HCO3-
279
Where does parallel Na+ / H+ and Cl- / HCO3- exchange take place?
Occurs in the ileum and colon most important in the interdigestive period
280
Where does epithelial Na+ channels (ENAC) occur?
Occurs in the colon (distal particularly) and is regulated by aldosterone
281
What are the major mechanisms of postprandial Na+ absorption in the jejunum?
Na+ / glucose and Na+/ amino acid co transport
282
Describe Na+/ H+ exchange in the jejunum
- occurs at both the apical (NHE2 and NHE3) and basolateral (NHE1) membranes, but only NHE2 and NHE3 contribute to trans-epithelial movement of Na+ and the regulation of intracellular pH
283
Which molecule is a 'cellular pH housekeeper'?
NHE1
284
Exchange at the apical membrane, in the jejunum is stimulated by what?
The alkaline environment of the lumen (ie. high pH = low proton concentration) due to the presence of bicarbonate from the pancreas
285
What is the primary mechanism of Na+ absorption in the inter-digestive period?
Na+/H+ and Cl=/HCO3- exchange in parallel
Occurs in the ileum and proximal colon
Does not greatly contribute to postprandial absorption
286
What mediates electrogenic Na+ absorption in the distal colon?
Epithelial Na+ channels (ENAC)
287
What are the three actions of aldosterone?
- opens ENAC (seconds)
- inserts more ENAC into membrane from intracellular vesicle pool (minutes)
- increases synthesis of ENAC and Na+/K+ ATPase (hours)
288
How can Cl- absorption occur passively?
Via the transcellular or paracellular routes
289
What is the driving force provided in the small intestine for Cl- absorption?
Provided by lumen negative potential due to electrogenic transport of Na+
290
What is the driving force provided in the large intestine for Cl- absorption?
Provided by lumen negative potential due to electrogenic movement of Na+ through NEAC
291
Name the other mechanisms of Cl- absorption
- Cl- HCO3- exchange (ileum, proximal and distal colon)
| - parallel Na+ H+ and Cl-- HCO3- exchange (ileum and proximal colon)
292
Cl- secretion occurs at what rate and is usually overshadowed by what?
- occurs at a basal rate
| - usually overshadowed by a higher rate of absorption
293
Cl- secretion occurs from what cells?
Crypt cells
294
Name the three process involved in Cl- secretion on the basolateral membrane
- Na/K+ ATPase
- Na+/K+/2Cl- co transported (NKCC1)
- K+ channels (IK1 and BK)
295
Secretion occurs when CFTR is indirectly activated by what?
- bacterial enterotoxins (eg. cholera toxin, heat stable enterotoxin, c diff)
- hormones and neurotransmitters (eg. vasoactive intestinal peptide, guanylin, Ach, bradykinin, 5-HT)
- immune cell products (eg. histamine, prostaglandins)
- some laxatives (eg. bile acids)
296
Activation of CFTR occurs indirectly as a result of what?
- second messengers that include;
- cAMP
- cGMP
- Ca2+
297
The Cl- conductance mediated by CFTR results from what?
- opening of channels at the apical membrane
- insertion of channels from intracellular vesicle into the membrane
- overall effect is secretory diarrhoea
298
Misoprostol enhances secretion of what?
CFTR
299
Name causes of diarrhoea
- impaired absorption of NaCl
- non-absorbable or poorly absorbable solutes in intestinal lumen
- hypermotility
- excessive secretion
300
What exploits SGLT1?
Rehydration therapy
301
Oral rehydration salts contain what?
- glucose 20g
- sodium chloride 3.5g
- sodium bicarbonate 2.5g
- potassium chloride 1.5g
- dissolved in a volume of 1l drinking water
302
Describe SGLT1
1. 2 Na+ bind
2. affinity for glucose increases, glucose binds
3. Na+ and glucose translocate from extracellular to intracellular
4. Na+ dissociate affinity for glucose falls
5. glucose dissociates
6. cycle is repeated
303
The actions of opiods on the alimentary tract include what?
- inhibition of enteric neurones (hyperpolarisation via activation of u-opiod receptors)
- decreased peristalsis, increased segmentation ( ie constipating)
- increased fluid absorption
- constriction of pyloric, ileocaecal and anal sphincters
- increased tone of large intestine
304
The major opioid agonists used in diarrhoea are?
- codeine
- diphenoxylate (low CNS penetration, low solubility in water, decreased abuse potential, many preparations contain atropine)
- loperamide (low CNS penetration, low solubility in water, undergoes enterohepatic recycling)
