Physiology Flashcards
1
Q
What is the function of lips,cheeks and tongue?
A
to keep food moving and place it in the optimal position for effective chewing.
2
Q
What are the main muscles involved for food to be masticated (chewed)?
A
Masseter and temporalis- bring lower jaw up against upper jaw
Pterygoids- open jaws, keeps them aligned and moves them up down and side to side.
3
Q
What nerve controls the muscles of mastication?
A
Trigeminal nerve (vth cranial)
4
Q
Describe the roles of the different teeth in the mouth.
A
Incisors- sharp edges to cut tough food
canines- sharp end to to grind food
premolars and molars- complex surfaces that capture small bits of food and crush food.
5
Q
what does the term sublingually mean?
A
Under the tongue
6
Q
What are the advantages of sublingual prescription?
A
the need to swallow drug is avoided and so bypasses the liver and avoids hepatic first-pass metabolism.
7
Q
What are the salivary glands?
A
parotid,submandibular and sublingual glands.
8
Q
Saliva is hypertonic true or false?
A
false its hypotonic
9
Q
What nerves are responsible sending impulses from the brainstem salivary nuclei for salivary secretion and what fibres are involved?
A
Facial (vii cranial)
Glossopharyngeal (IXth cranial)
Parasympathetic fibres
10
Q
What is xerostomia and why does it occur with antidepressants, tranquilizers and opiate analgesics?
A
Xerostomia- dry mouth
These drugs inhibit parasympathetic nerve activity which therefore inhibits salivation.
11
Q
What are the main roles of salivation?
A
- Moisten and lubricate the mouth to form bolus
- Dissolve food molecules so they can react with taste receptors
- Ease swallowing of bolus
- Begin digestion- contains alpha amylase which breaks down of polysaccharides
12
Q
How does saliva help against infection and tooth decay?
A
- Coats teeth with proline-rich protein(pellicle) as protective barrier on its surface.
- Contains immunoglobulins and antimicrobials that maintain control of the residen bacterial flora of the mouth and prevent serious infection.
13
Q
Describe the formation of saliva
A
- Stimulation of acinar epithelial cells cause ca2+ dependent activation of K+ and CL- channels.
- Efflux of cl- cause Na+ to move through the glandular ducts via paracellular route. Creating concentration gradient for water to move into luminal space via osmosis.
- Na+ and CL- are reabsorbed by ENaC and CL- HCO3- exchange.
- HC03- and K+ are secreted- creates hypotonic saliva.
14
Q
Which nerve innervates the tongue muscle?
A
hypoglossal (XIIth cranial) nerve.
15
Q
Sensory fibres from the tongue travel through which nerves?
A
Glossopharyngeal (IXth cranial) nerve
and chorda tympani branch of facial (VIIth cranial) nerve
16
Q
What are the functions of the tongue?
A
directs and retrieves food between the teeth
clears obstructions
propels food posteriorly to initiate pharyngeal phase of swallowing
speech
17
Q
What are the major modalitlies of taste?
A
- Sweet
- sour
- salt
- bitter
- umami
18
Q
What nerve runs alongside the oesophagus and innervates oesophageal muscle?
A
Vagus nerve.
19
Q
What is the role of the submucosal venous plexus?
A
Drains venous blood from the oesophagus avoiding the hepatic portal vein and liver.
20
Q
What happens to oesophageal veins during portal hypertension?
A
Collateral veins divert gastric blood to oesophageal veins, which enlarge and form varices.
21
Q
What is peristalsis?
A
a coordinated wave of contraction behind the bolus of food, with relaxation ahead of it, propelling bolus forward. Down the oesophagus
22
Q
What causes peristalsis to occur?
A
along with controlling sphincter movement, vagus nerve and the enteric nervus plexus, which is in the tract itself. controls peristalsis
23
Q
How does vomiting occur?
A
When peristalsis waves move in the opposite direction. i.e towards the mouth
24
Q
Describe the stages of swallowing.
A
- Tongue forces bolus down into oropharynx. UOS closed
- This initiates a reflex which raises the soft palate thus sealing off the nasopharynx preventing food entering the nasal cavity. This inhibits respiration
- Superior and middle pharyngeal constrictor force the bolus down in the hypopharynx and the glottis closes.
- Epiglottis is forced backwards and downwards
- this prevents food from entering the trachea.
- The UOS relaxes and these changes reverse. Larynx opens allowing breathing to occur.
25
What controls swallowing?
swallowing centres in the medulla
26
What is the difference between the first two waves of peristalsis?
1. primary peristaltic wave, which occurs when the bolus enters the oesophagus during swallowing. The primary peristaltic wave forces the bolus down the oesophagus and into the stomach in a wave lasting about 8–9 seconds. The wave travels down to the stomach even if the bolus of food descends at a greater rate than the wave itself, and continues even if for some reason the bolus gets stuck further up the oesophagus.
2. In the event that the bolus gets stuck or moves slower than the primary peristaltic wave (as can happen when it is poorly lubricated), stretch receptors in the oesophagal lining are stimulated and a local reflex response causes a secondary peristaltic wave around the bolus, forcing it further down the oesophagus, and these secondary waves continue indefinitely until the bolus enters the stomach.
27
What is the third wave of peristalsis?
it is a pathogenic caused form.
28
What are the main functions of the stomach?
store food
digest food
regulate the release of chyme
secrete the intrinsic factor.
29
What is the role of the intrinsic factor
Binds to Vitamin B12 protecting it from being absorbed in the proximal intestine.
30
What is the volume of the stomach when empty vs it being fully distended?
50 ml vs 4 L
31
Why is the storage of food important in the stomach?
As the stomach can ingest food more rapidly than it can digest it.
32
What are proteins broken down into and what type of enzyme does this?
Proteins are broken down into polypeptides
Pepsin is the type of enzyme.
33
What is the inactive form of pepsins called?
pepsinogen.
34
Where are pepsinogens found?
Produced by chief cells found in the gastric mucosa's glands.
35
How are pepsinogens activated?
HCL
36
What cells produce HCL in the stomach to lower the pH?
Parietal cells.
37
What else do parietal cells produce?
Intrinsic factor.
38
Where are parietal cells found in the stomach?
Found in the gastric mucosa's glands.
39
Describe the formation of HCL inside the parietal cells.
1. H+ ions are made by H2O being broken down via hydrolysis
2. H+ ions are transported out of the cell on the apical surface via a Proton pump ( h+-K+ ATPase protein) entering the lumen
3. CL- enters the cell on the basolateral side in exchange for HCO3- via another proton pump
4. CL- then via an apical chloride channel enters the lumen
40
Describe the formation of HCO3- in the parietal cells?
CO2 and H20 internally bind via carbonic anhydrase to form carbonic acid ( h2co3)
This breaks down into H+ and HCO3-
41
What is the main role of HCO3- in the stomach
Used to raise the pH in the alkali tide after the stomach has secreted acid.
42
What are the three stages of gastric secretion?
Cephalic phase
Gastric phase
intestinal phase
43
What causes the cephalic phase to occur?
the sight, smell, taste and mastication of food
44
When does gastric phase occur?
when food reaches the stomach
45
What stimulates acid secretion during the cephalic phase?
activation of the vagus nerve via the medulla oblongata and its actions on the enteric plexus.
46
how does vagal stimulation cause the release of HCL and pepsin?
the postganglionic parasympathetic fibres cause the release of Acetylcholine.
It also releases GRP which causes the release of Gastrin from G cells.
Causes release of histamine from ECL cells.
inhibits D cells- this, in turn, reduces the inhibitory effect of somatostatin on G- cells.
Ach, gastrin and histamine stimulate release of H+ from parietal cells.
47
What pathways are used to stimulate HCL in the cephalic phase?
Direct- Ach, gastrin and Histamine act on M2 muscarinic and H2 receptors to stimulate parietal cells
indirect- ACH and gastrin stimulate ECL cell resulting in release of histamine acting on LOCAL. parietal cells.
48
What are the main stimuli for the gastric phase?
distention of stomach
chemical composition of the food.
49
What does the distention of the stomach do to the mechanoreceptors?
they are stretched thus making longer vagovagal reflexes and setting up local myenteric reflexes
50
How does the break down of proteins affect gastric secretion?
the release of peptides and free amino acids directly stimulate G cells to relase Gastrin
51
Why is gastrin described as self-regulating?
at pH 3 or below gastrin stops being produced. This occurs due to decreased buffering of HCL. Therefore when there is no food there is a low pH and so gastrin is inhibited via release of somatostatin from D cells.
52
What is chyme?
it is semi-fluid material which food is converted into after the stomach.
53
How is histamine regulated?
PGE2 continually secreted by the gastric mucosa in the gastric phase acts locally to reduce histamine.
54
What is the effect of chyme when in the pyloric antrum?
it causes the duodenum to distend
Antral contraction
opening of pyloric sphincter
55
What increases the rate of gastric emptying?
Volume of chyme in the antrum
fall in pH of chyme.
56
What decrease rate of gastric emptying?
Distention of duodenum
Presence of fats and decrease of pH in the duodenum lumen. Needs to be neutralised and fat to be absorbed
Hypertonicity - products of carbs ad protein digestion draw water into small intestine- danger of reduced plasma volume and circulatory disturbances (e.g. ‘dumping syndrome’)
57
How does duodenum delay gastric emptying?
Neuronal response- enterogastric reflex which decreases activity by signals from intrinsic nerve plexuses and the ANS
Hormonal response- release of enterogastrones inhibits stomach contractions
58
What are the two sections of the stomach based on its mechanical activity?
Orad stomach
caudad stomach
59
Does the Orad region have slow-wave activity true or false?
false
60
What type of contractions occur in orad region?
tonic contractions
61
Why are the tonic contractions weak?
Because of the thin musculature in that region
62
What makes up the orad stomach?
fundus and proximal body
63
What makes up the caudad region?
distal body and antrum
64
what is gastric slow wave?
Rhythmic electric activity in the caudad stomach produces regular peristaltic waves (3min-1)
65
What are the three sections of the small intestine?
Duodenum,jejunum and ileum
66
What happens when chyme first enters the duodenum?
Intestinal phase:
| continuation of gastric secretion due to duodenal G cells
67
What does the small intestine receive from other organs?
chyme- stomach
Pancreatic juice - pancreas
bile - liver and gall bladder
68
What is segmentation?
Mixing of chyme in the digestive state in a circular motion
69
How does segmentation occur?
alternating contraction and relaxation of circular muscle are initiated by pacemaker cells which cause the basal electrical rhythm (BER)
70
When is segmentation in the duodenum initiated?
when BER has hit the threshold which occurs when duodenum distends.
71
compare segmentation contractions between duodenum, jejunum and ileum.
Duodenum and jejunum has more frequent contractions then ileum
duodenum and jejunum = 12 min-1
Ileum = 9 min-1
72
When is segmentation in the ileum initiated?
Triggered by gastrin in the stomach via gastroileal reflex
73
What is the role of secretin in the duodenum?
inhibits the release of gastrin
stimulates the release of pancreatic and biliary HCO3-
74
What cells produce secretin?
S cells in the duodenum
75
What cells produce CCK?
I cells in the duodenum and jejunum
76
When is secretin released?
in response to detection of H+ and fatty acid in the lumen
77
What are the two types of contractions in the small intestine?
Mixing (segmentation)
| propulsive (peristalsis)
78
What happens during segmentation?
A portion of SI becomes distended with chyme
Intestinal wall elicit localised concentric contractions spaced at intervals along the tract.
spaced segments form along the intestine
as a set relaxes another segmentation contracts usually between the two old points.
79
What are the principal effects of the myenteric plexus when it is stimulated?
1. increased tonic contraction of the gut wall
2. increased intensity of the rhythmical contractions
3. Slightly increased rate of the rhythm of contraction
4. Increased velocity of conduction of excitatory waves along the gut wall, causing more rapid movement of the gut peristaltic waves
80
What are the two main plexuses which makes up the ENS?
1. Myenteric plexus
| 2. Submucosal plexus
81
What is the main role of the submucosal plexus?
Regulates epithelial cell and submucosal blood vessel function
82
What are the three types of GI reflexes?
Give examples of each
1. Local reflexes Integrated entirely within the gut wall ENS- mainly involved in movement
examples
secretion,
peristalsis
2. short reflexes from the gut to the prevertebral sympathetic ganglia and then back to GI tract
examples
gastrocolic reflex ( stomach to colon) or enterogastric reflexes ( inhibit gastric motlilty from colon and SI)
3. Long reflexes from the gut to the spinal cord/brain stem and then back to tract-:
These include stomach to brain stem to stomach for gastric motor and secretory activity
examples
Pain reflexes
Defecation reflexes ( gastro ileal)
83
Discuss the pathway of chyme in the small intestine via peristalsis.
propels chyme from the pylorus to the ileocaecal valve
84
What is the role of peristalsis in the small intestine?
1. move chyme through tract
| 2. Spread chyme out along the intestinal mucosa
85
What stimulates peristalsis in the SI?
1. Greatly increased after a meal
2. Gastroenteric reflex
3. gastrin, CCK, insulin and serotonin increase intestinal motility
86
What inhibits peristalsis
| in SI?
1. No chyme present
2. Secretin
3. Glucagon
87
What is the difference between segmentation and peristalsis ?
1. Segmentation pushes chyme in both directions but net movement is slightly aboral
Peristalsis pushes chyme in one direction (aborally)
2. Segmentation relies on circular muscular contraction
Peristalsis relies on rhythmic longitudinal muscular contraction
3. segmentation doesn't occur in oesophagus and stomach
88
What is the peristaltic rush?
strong waves of contraction which is caused by intense irritation of the intestinal mucosa.
These powerful contractions travel long distances sweeping the contents of the intestine into the colon relieveing it of chyme and excessive distention.
89
What is the role of the ileocecal valve?
prevents backflow of chyme into the ileum
90
What is the effect of the gastroileal reflex on the ileocecal valve?
ileocecal may prevent food entering the cecum until the person may eat another meal
Gastroileal reflex intensifies the peristalsis waves forcing the remaining chyme through.
91
Discuss how the cecum controls the ileocecal sphincter and ileal peristalsis
1. When cecum becomes distended - sphincter becomes intensified
This leads to ileal peristalsis being inhibited
2. irritation of cecum delays emptying
92
What is the migrating motor complex?
Strong peristaltic contractions which clear debris and mucus and sloughed epithelial cells between meals.
93
what stimulates MMC?
Molitin
94
What inhibits MMC?
feeding and vagal activity
Gastrin and CCK
95
What is CCK released in response to?
```
Release of :
monoglycerides
free fatty acids
Amino acids
Small peptides
```
96
What is the role of CCK?
1. Inhibit gastric emptying (inhibits release of gastrin and acid)
2. Cause secretion of pancreatic enzymes
3. stimulates relaxation of the sphincter of Oddi
4. Stimulates contraction of the gall bladder to eject bile from the duodenum
5. potentiates the action of secretin
97
Where is GIP produced?
K cells of duodenum and jejunum
98
What is GIP released in response to?
Presence of
Glucose
amino acids
fatty acids
99
What is the role of GIP?
Stimulate release of insulin
Inhibit gastric emptying
100
Where is GLP-1 produced?
L cells
101
What is GLP-1 produced in response to?
presence of food in SI.
102
What is the role of GLP-1?
Stimulates insulin secretion
Inhibits glucagon secretion
Decrease gastric emptying and appetite
103
Where is Motilin produced?
M CELLS of duodenum and jejunum
104
What is motilin secreted in response to?
secreted during a fasting state
105
What is the role of motilin?
initiates MMC
106
What type of receptor do all peptide hormones act on?
G-protein coupled receptors.
107
Where is ghrelin produced?
Gr cells of the gastric antrum
108
What is the role of ghrelin?
Stimulates appetite.
109
where is vitamin b12 absorbed?
Terminal ileum
110
What is succus entericus?
intestinal juices
111
What is the role of the Brunner's glands?
Produces alkaline mucus to prevent digestion of duodenal wall from highly acidic gastric juices.
It also produces the mucus as it contains a large number of bicarbonate ions which is used to neutralise the HCL as well
112
What stimulates the Brunner's glands?
1. Tactile or irritating stimuli on the duodenal mucosa
2. vagal stimulation - increase in stomach secretion= increase in brunner's gland secretion
3. GI hormones e.g. CCK, gastrin especially SECRETIN
113
What inhibits the Brunner's glands
Sympathetic stimulation- suggests why very excitable people have peptic ulers in the duodenal bulb
114
What are the properties of the crypt of lieberkuhn which make it effective with intestinal secretion?
1. contains goblet cells- secrete mucus which lubricates and protects intestinal surfaces
2. Contains enterocytes which secrete large quantities of water and electrolytes. Eventually reabsorbing them with end products of digestion. Also absorb carbohydrates,proteins fats and vitamins.
115
What does the small intestine absorb?
1. water
2. electrolytes
3. carbohydrates
4. amino acids
5. minerals
6. fats
7. vitamins
116
What enzymes are released from enterocytes in the brush border?
1. peptidases e.g. carboxypeptidase and aminopeptidase
| 2. sucrase, maltase, isomaltase and lactase
117
What are the properties of the small intestine which make it adapted for absorption?
1. large surface area - plicae circulae - transverse folds
villi which are finger-like projections of lumen
microvilli which are finger-like projections of the apical surfaces of the enterocytes
2. rich blood supply- each villus contains a capillary network
3. epithelial cells are replaced every 6 days
118
Discuss the ways sodium ions are move into the mucosa.
1. Na+/glucose co-transport
2. Na+/amino acid co-transport
3. Na+/H+ exchange
4. Parallel Na+/H+ and Cl-/HCO3- exchange
5. epithelial Na+ channels ( ENaC)
119
What two ways can water enter the blood?
1. transcellular
| 2. paracellular
120
For na+/H+ exchange in the jejunum, what antiporters are used?
1. Apical side - NHE2 and NHE3
| 2. Basolateral NHE1
121
what stimulates the exchange of the apical membranes in the jejunum?
the alkaline environment of the lumen (low H+ concentration)
122
Parallel Na+/H+ and Cl-/HCO3- exchange occurs where and when?
1. in the ileum and proximal colon
| 2. Interdigestive period
123
What are the differences between Parallel Na+/H+ and Cl-/HCO3- exchange and cotransport exchange?
1. Cotransport is electrogenic while the parallel exchange is electroneutral
2. Cotransport is not regulated by intracellular cAMP
3. co-transport mainly occurs in the jejunum while parallel is in the ileum
124
Where do ENaC help in absorption of NA+?
distal colon
125
How does aldosterone help in absorption of Na+
Released when feeling dehydrated
1. Open ENaC channels
2. Inserts more into the apical membrane from intracellular vesicle pool
3. increases the synthesis of ENaC and Na+/K+ Atpase
126
Discuss the formats in which chloride ions are absorbed into the intestines.
1. diffuse via transcellular or paracellular. Exchange systems are also used
2. Small intestine- lumen has negative potential due to transport of sodium
3. Large intestine - lumen has negative potential due to ENaC movement of Na+
127
where are CL- ions are secreted from?
Crypt enterocytes
128
Discuss the secretion of CL-
1. chloride ions are absorbed from the blood into the cell via low intracellular Na+ which causes a drive of sodium , potassium and chloride ions via NKCC1
2. High conc of Cl- means that diffuses out of cell through apical membrane via CFTR
129
What activates CFTR
1. Bacterial enterotoxins- diarrhoea causing
2. Hormones and neurotransmitters
3. Immune cells products
4. cAMP
5. gGMP
6. Ca 2+
7. some laxatives
130
Discuss the reabsorption of water via the small intestine.
1. Sodium ions are actively transported on the basolateral side of the villus cells via Atpase (3 for 2 K+)
2. Creates conc gradient for Na+ to diffuse into cell via apical membrane
3. high conc of K+ in the cell means it diffuses back out of cell via basolateral membrane along with Cl-. creating ionic enviromment in the blood
4. creates an osmotic enviroment in the lumen causing water to be reabsorbed ( released from crypt first).
5. Water diffuses down the gradient into the cell and then transported into the blood.
131
What is the role of paneth cells?
they are involved in protein synthesis,secretion and contain antibacterial proteins such as lysozyme,phospholipase A2 and defensins
132
What is the role of acinar cells in the pancreas?
It secretes the pancreatic juice
133
What is pancreatic juice secreted in response to?
the detection of chyme.
Hormone release of CCK
134
What is the pancreatic juice made up of?
1. Bicarbonate ions
2. Water
3. Enzymes
135
What enzymes are present in the pancreatic juice?
What are their functions?
1. Pancreatic amylase- breaks down carbohydrates into monosaccharides
2. Pancreatic lipase- breaks down fats into glycerol and fatty acids.
3. ribonuclease and deoxyribonuclease- break down nucleic acids and free mononucleotides
4. PROTEOLYTIC ENZYMES- MOST IMPORTANT. This includes trypsin, chymotrypsin and carboxypeptidase.
Trypsin and chymotrypsin break down proteins into peptides of various size but not individual amino acids
carboxypeptidase splits peptides into individual amino acids
136
What are the names of the inactive forms of:
1. trypsin
2. chymotrypsin
3. carboxypeptidase
1. Trypsinogen
2. chymotrypsinogen
3. procarboxypeptidase
137
How are the three main proteolytic enzymes activated?
trypsinogen is activated by the enzyme enterokinase. This is secreted by the intestinal mucosa when chyme is detected
Trypsinogen can also be autocatalytically activated by trypsin
Chymotrypsinogen and procarboxypeptidase are activated by trypsin
138
Where is the trypsin inhibitor produced?
the cytoplasm of the glandular cells of the pancreas
139
what secretes water and bicarbonate ions from the pancreas?
epithelial cells of the ductules and ducts which lead from the acini.
140
discuss the secretion of bicarbonate ions and water from epithelial cells.
1. CO2 diffuses from the blood into the cell.
2. carbonic anhydrase combines water and CO2 to form carbonic acid
3. carbonic acid dissociates into bicarbonate ions and H+
4. More HCo3- ions diffuse into the cell via cotransport with Na+
5. bicarbonate ions leave cell on luminal border via secondary active transport with chloride ions
6. chloride ions reenter the cell via CFTR channels
7. H+ ions are actively exchanged with na+ on the basolateral side of the cell. K+/ H+ ATPase are also used.
8. Na+ ions diffuse from blood to negative voltage lumen via tight junctions between cells as well
9. Bicarbonate and sodium ions create an osmotic gradient for water to diffuse paracellular and transcellular.
10. Isosmotic bicarbonate environment in the lumen forms
141
pancreatic amylase and lipase are active in the acinar cells true or false?
TRUE!
142
What are the three hormones responsible for stimulating pancreatic secretion
1. Acetylcholine, which is released from the parasympathetic vagus nerve endings and from other cholinergic nerves in the enteric nervous system
2. Cholecystokinin (CCK), which is secreted by the duodenal and upper jejunal mucosa when food enters the small intestine
3. Secretin, which is also secreted by the duodenal and jejunal mucosa when highly acidic food enters the small intestine
143
What is the main difference between acetylcholine and CCK vs secretin?
Acetylcholine and CCK stimulate the release of pancreatic enzymes
secretin stimulates the release of water and electrolytes which are required to move the enzymes into the duodenum
144
What are the three phases of a pancreatic secretion called?
1. cephalic
2. gastric
3. intestinal
145
What happens in the cephalic stage?
20 % of pancreatic enzymes are secreted due to acetylcholine after vagal stimulation (mainly acinar cells)
146
What happens in the gastric stage?
5-10% of pancreatic enzymes are secreted due to gastric distention. Caused by a vagovagal reflex. (acinar and duct cells)
147
What happens in the intestinal phase?
Secretin
chyme enters the duodenum. Secretin is released which stimulates the release of pancreatic juice. It is released in response to HCL in chyme
The sodium bicarbonate neutralises the HCL in the chyme to form NaCl and H2Co3 ( carbonic acid). The carbonic acid immediately dissociates with the co2 being expelled via the lungs. Thus raising the pH in the duodenum.
CCK
Chyme enters the duodenum. it is secreted in response to fatty acids and proteins
This stimulates the release of pancreatic enzymes in the acinar cells.
This results in the digestion of the fatty acids and proteins
148
Which cells secrete insulin in the pancreas?
beta cells
149
Which cells secrete glucagon in the pancreas?
alpha cells
150
which cells secrete somatostatin in the pancreas?
D cells
151
What is the role of the sphincter of oddi?
to control the secretion of pancreatic juice and bile
152
What is the role of the liver?
Metabolism
1. Carbohydrate metabolism
2. Fat metabolism
3. Protein metabolism
4. Hormonal metabolism
Exocrine function
1. Storage
2. secretion of bile
3. synthesis of protein
4. Detoxification
5. Protection
153
Give examples of carbohydrate metabolism in the liver
1. gluconeogenesis – to produce glucose from amino acids
2. glycolysis – to form pyruvate thence lactate (anaerobic conditions), or acetyl-coA (aerobic conditions)
3. glycogenesis – to store polymerised glucose, as glycogen
4. glycogenolysis – to release glucose, as required
154
Give examples of fat metabolism in the liver.
1. processing of chylomicron remnants
2. synthesis of lipoproteins (e.g. VLDLs, HDLs; for export) and cholesterol (for steroid hormone and bile acid synthesis)
3. ketogenesis (in starvation) – important for neuronal function
155
Give examples of protein metabolism in the liver.
1. synthesis of plasma proteins
2. transamination and deamination of amino acids
3. conversion of ammonia to urea
156
Give examples of hormonal metabolism in the liver
```
Inactivation of:
insulin
glucagon
anti-diuretic hormone (ADH, vasopressin)
steroid hormones
```
Activation of:
Thyroid hormone: Thyroxine to triiodothyronine
Vitamin D to conversion of vitamin D to 25-hydroxyvitamin D2 (calcifediol) – further activation to 1,25-dihydroxyvitamin D3 occur s in kidney
157
Give examples of molecules stored by the liver.
1. Glycogen
2. Water soluble vitamins: A,D,E and K.
3. Fat soluble vitamins: B12
4. Iron and copper.
158
What cells store vitamin A in the liver?
ito cells
159
What cells store vitamins D,E and K in the liver?
Hepatocytes
160
What proteins are synthesised in the liver?
1. Albumin
2. complement proteins
3. apolipoproteins
4. carrier proteins
5. coagulation factors II, VII, IX and X
161
How does the liver help in protecting the body?
1. Detoxification of ethanol and drugs
2. contains Kupfer cells
3. Acts as a blood resevoir
4. produce host defense proteins
5. Maintains blood glucose concentration
Hypoglycemia=neuroglycopenia
Hyperglycemia= diabetes mellitus
162
What is bile made out of?
1. Bile salts
2. bile pigments
3. Cholesterol
4. Lecithin
5. mucus
6. Bilirubin
7. IgA
8. Water
9. electrolytes
163
What does the bile acid- dependent fraction consist of?
1. Bile salts
2. bile pigments
3. Cholesterol
4. Lecithin
5. mucus
6. Bilirubin
7. IgA
164
What does the bile acid- independent fraction consist of ?
water and electrolytes
165
Where is the bile acid-dependent fraction secreted?
Hepatocytes
166
Where is the bile acid- independent fraction secreted from?
cholangiocytes-epithelial cells lining the bile duct
167
What causes the hepatic acute phase response?
Inflammation which causes the release of interleukin 6
168
What occurs during the hepatic acute phase response?
Synthesis of host defense proteins
reduces albumin synthesis
169
Give examples of acute defense proteins.
1. CRP
2. serum amyloid A
3. secretory phospholipase A2
170
What is the role of bile?
1. Emulsify and break down fats
2. Used in absorption of fats
3. bile serves as a means for excretion of several important waste products from the blood e.g. bilirubin and excess cholesterol
171
What is the role of the gallbladder?
stores bile
172
How can the gallbladder hold up to 450 millilitres despite having a volume of only 30-60 ml?
As it can absorb the water and the electrolytes into its mucosa thereby storing the rest of the bile components?
173
How does the gall bladder absorb the electrolytes and water?
Most of this gallbladder absorption is caused by active transport of sodium through the gallbladder epithelium, and this transport is followed by secondary absorption of chloride ions, water, and most other diffusible constituents.
174
How does this effect the bile concentration in comparison to hepatic bile?
this makes bile salts , bilirubin ,cholesterol and lecithin more concentrated
175
What is the role of cck for bile secretion?
1. Opening of the sphincter of oddi
| 2. Gall bladder contraction.
176
What causes gall bladder contractions?
1. CCK
| 2. Vagal stimulation
177
What is the role of secretin on bile secretion?
Increases the secretion of bile acid-independent fraction of bile
178
Why is it useful that bile is alkaline?
Neutralises chyme
protects duodenum mucosa
acts as a pH adjustment for digestive enzymes.
179
Discuss how cholesterol forms into bile salts.
The cholesterol is first converted to cholic acid or chenodeoxycholic acid via hepatocytes. These acids in turn combine principally with glycine and to a lesser extent with taurine to form glyco- and tauro-conjugated bile acids.
180
What is the function of bile salts?
1. acts as emulsifier for fat gobules
| 2. Form micelles in lipids which allow them to be absorbed in the mucosa
181
Discuss the process of enterohepatic circulation.
1. Bile salts either are absorbed in the duodenum by diffusion. Or absorbed in the distal ileum via active transport
2. a small fraction of bile salts are broken down by intestinal bacteria in the lumen into secondary bile acids. Secondary bile acids once in the liver conjugate with glycine or taurine to form bile salts
3. Carried by portal vein to liver
4. 5% of bile is lost in feces however this is made up by the the synthesis of bile via hepatic cholesterol
182
What are the two main lipoproteins exported from the liver?
1. Very low density lipoproteins (VLDL)
| 2. high density lipoproteins ( HDL)
183
Give examples of resin agents.
Colveselam, colestipol, colestyramine
184
What are the benefits of resin agents?
Bind to bile acids preventing their reabsorption.
This increases hepatic cholesterol synthesis which is required to turn bile acids into salts
Thus reducing amount of lower plasma LDL cholesterol which is being used up . Decreasing risk of atherosclerosis.
185
What are the benefits of lower plasma LDL cholesterol in the blood?
indirectly:
1. promote hepatic conversion of cholesterol to bile acids
2. increase cell surface expression of LDL-receptor in hepatocytes
3. increase clearance of LDL-cholesterol from plasma
186
Why are statins effective against hypercholesterolaemia?
Inhibits HMG-CoA reductase which is a rate limiting enzyme in cholesterol synthesis.
This in turns reduces cholesterol synthesis and increases LDL receptors thus lowering LDL plasma concentrations
187
What is the role of drug metabolism?
1. Convert parent drugs into more polar metabolites- facilitates excretion and prevents reabsorption in the kidneys
2. Convert drugs to metabolites that are usually pharmacological less active than the parent compound.
188
What occurs in phase 1 of drug metabolism?
1. Hydrolysis
2. oxidation
3. reduction
These all make drugs more polar allowing for conjugation
189
What occurs in phase 2 of drug metabolism
Conjugation- enzymes covalently link drugs with water-soluble moieties e.g. glucuronate,sulphate or alkyl group.
Makes them more water soluble and easier to excrete
190
What are the two main types of digestion in the small intestine?
Luminal digestion
Membrane digestion
191
What occurs in luminal digestion?
pancreatic enzymes break down large particles into smaller ones in the duodenum
192
What occurs in membrane digestion?
enzymes situated at the brush border of the enterocytes break down particles to be absorbed
193
How do humans store glucose as?
glycogen
194
What is sucrose made out of?
Glucose and fructose via alpha 1,2 linkage
195
What is lactose made of?
Glucose and galacatose via beta 1,2 linkages
196
What is the difference between amylopectin and glycogen?
1. Amylopectin is used as storage in plants while glycogen is for animals
2. Glycogen is more branched
197
What type of enzymes hydrolyse polysaccharides?
alpha-amylase
198
Where are the two types of alpha amylase used in breaking down polysaccharides?
1. Salivary glands amylase
| 2. pancreatic amylase
199
What are the products of hydrolysis of starch with alpha amylase?
produces mainly linear gluocse ogliomers
1. Maltose (mainly)
2. Maltotriose
3. limit dextrins
Lactose and sucrose will present in the diet but not broken down by amylase
200
What stops salivary amylase from continuing the break down of starch in the stomach?
pH below 4.0 makes amylase inactive.
201
Why do we have pancreatic amylase?
Not all of the starch has been hydrolysed into maltose due to the salivary amylase being inactive in the stomach.
Need to convert starch into ogliosaccharides for membrane digestion.
202
Why can alpha amylase not produce glucose from polysaccharides?
1. cannot break down terminal alpha 1,4 linkages only internal ones
203
Why are alpha limit dextrins a product of hydrolysis by alpha amylase?
1. Because it cannot break down alpha 1,6 linkages at branch point
2. cannot break down 1,4 linkages adjacent to these branch points
204
What are the ogliosaccharidases?
1. lactase
2. sucrase
3. maltase
4. isomalatase (alpha dextrinase)
205
where are ogliosaccharidases produced and where are they found ?
Produced by enterocytes and are found in the brush border of the mucosa of the small intestine
206
What is the co transporter involved in the absorption of Glucose and galactose in the duodenum and jejunum?
SGLT1 - sodium-glucose co- transporter
207
What transporter is required for the absorption of fructose?
GLUT5
208
what is the difference between the the absorption of glucose/galactose and fructose?
1. SGLT1 is a co transporter while GLUT5 isnt
| 2. Glucose and galactose enter via secondary active transport while fructose enters via facilitated diffusion
209
Describe the process of the absorption of monosaccharides.
1. Basolateral Na+/k+ pump actively removes 3 sodium ions from the enterocyte
2. creates a concentration gradient for sodium which enters via SGLT1 with glucose and galacatose in the apical membrane
3. Fructose enters in enterocyte due to already high concentration in the lumen
4. Conc gradient allows for all three forms to diffuse into blood via GLUT 2
210
What transporter is used in the facilitated diffusion of the monosaccharides on the basolateral side of the enterocytes?
GLUT2
211
What is the optimum pH for pepsin?
1.8-3.5
212
What are the differences between endopeptidases and exopeptidases
endopeptidases cleave at non terminal bonds
exopeptidases cleave at terminal bonds
213
Give examples of endopeptidases
1. pepsin
2. Trypsin
3. chymotrypsin
4. elastase
214
Give examples of exopeptidases
1. Procarboxypeptidase A
| 2. Procarboxypeptidase B
215
What are the products of a endopeptidase reaction?
ogliopeptides
216
What are the products of a exopeptidase reaction?
amino acids and ogliopeptides
217
What bond is broken between proteins during hydrolysis? (primary structure)
peptide bonds
218
What is the role of enterokinase?
To activate tryspinogen
219
what are the main forms of peptides which enter the duodenum and the brush border?
tri and dipeptides
220
What does pepsin convert proteins into ?
1. polypeptides
2. proteoses
3. peptones
221
What are the two types of enzymes found in the brush border?
1. Aminopolypeptidase
| 2. dipeptidases
222
what do are the role of the brush border peptidases>?
convert few remaining polypeptides to tri and dipeptides
223
What is the role of cytoplasmic peptidases?
convert the di and tri peptides intosingle amino acids
224
where are the cytoplasmic peptidases found?
in the cytoplasm of the enterocyte
225
Discuss the amino acid absorption at the brush borders.
1. 5 different Na+ dependent co transporters - neutral, aromatic, imino, positively and negatively charged amino acids
2. 2 different Na+ sodium independent co transporters
226
Give example of a na+ dependent transporter at the brush border.
SLCA19 - used for neutral amino acid
227
Give example of Na+ independent transporter at brush border?
SLC7A(- ussed for cationic aminoacids
228
Discuss the amino acid absorption at the basolateral membrane of the enterocyte.
3 mediate efflux of amino acids- Na+ independent
2 mediate influx - Na+ dependent - enterocytes need amino acids !
net movement is bidirectional
229
Discuss the ogliopeptides absorption at bush border.
H+ dependent pathways using the transporter e.g. PepT1 and SLC15A
They are then hyrdolysed into amino acids
230
what bond is broken between polysaccharides during hydrolysis?
glycosidic bonds
231
What is the name given to the lymphatic channel which are found in the villi?
lacteal
232
What promotes emulsification in the GI tract?
1. Chewing ( not that important)
2. gastric churning
3. peristalsis and segmentation
233
What is a saturated fatty acid?
Fatty acid with only single carbon bonds
234
What is an unsaturated fatty acid?
Fatty acid with at least one double carbon bond
1 double carbon bond = monounsaturated
2 or more = polyunsaturated
235
What is the methyl end of a fatty acid called?
omega end.
This is used to distinguish where the double bond is in the fatty acid in relation to the methyl end e.g. omega 3
236
Give examples of amphiphilic molecules
biliary phospholipids (lecithin)
cholesterol
bile salts
237
What are the roles of amphilphilic molecules?
Form emulsion droplets which help break down dietary lipids by increasing the surfarce area to volume ratio
238
What is gastric lipase secreted in response to?
gastrin
239
Where does gastric lipase break triglycerides into?
Diglyceride and free fatty acid
240
What is the importance of the free fatty acid?
Stimulates the release of CCK which stimulates the production of pancreatic lipase
241
What position does gastric lipase normally break down triglycerides?
At position 3
242
What environment is required for pancreatic lipase to act at their most optimum activity?
1. Colipase co-factor
2. Alkaline pH
3. Ca2+
4. Bile salts
5. fatty acids
243
What points do pancreatic lipase mainly hydrolyse triglycerides at?
position 1 and 3
244
Give examples of dietary lipids
1. Triglycerides
2. phospholipds
3. Cholesterol and cholesterol esters
4. free fatty acids
245
What type of fatty acids are absorbed in the stomach?
short and medium fatty acids
246
What lipase are present in the stomach.
gastric lipase
lingual lipase
247
What are the primary products of hydrolysis of triglycerides by pancreatic lipase?
1. Fatty acids
| 2. 2-monoglycerides
248
What is the role of bile salts?
Form mixed miscelles
249
What is the role of colipase?
Allow lipase to bind to the triglycerides which the bile salts blocked.
250
What is the inactive form colipase
procolipase
251
What activates procolipase?
trypsin
252
Discuss the formation of mixed micelles.
Triglycerides on the surface of the emulsion droplets are broken down into their products.
These emulsion droplets reduce in size as these lipids are broken down.
the final products are the micelles
253
which enzyme hydrolyse cholesterol ester?
Cholesterol ester hydrolase
254
Which enzyme hydrolyse phospholipids?
phospholipase A2
255
what are the digested lipids which enter the enterocytes?
1. Fatty acids
2. monoglycerides
3. cholesterol
256
How do digested lipids enter the enterocytes?
1. passive diffusion
| 2. facilitated diffusion via fatty acid translocases, fatty acid bind proteins and fatty acid-transport proteins
257
Discuss the difference in lipid absorption between short /medium chained fatty acids and long chained fatty acids.
short/medium chain diffused into cytoplasm of enterocyte and then straight into the villus capillaries via basolateral end
Long chain
Long chain are re-esterified to triglycerides and then complexed with apolipoproteins in the endoplasmic reticulumv to form chylomicrons
Chylomicrons then enter the lacteal (lymph system)
258
Discuss how cholesterol is absorbed.
Endocytosis in clatherin coated pits by NPC1L1 protein
259
Discuss the pathways the different for Calcium ions to be absorbed
1. Acitve transport in the duodenum (transcellular)
| 2. diffusion whole of small intestine ( paracellular)
260
Where are parathyroid hormones released from?
parathyroid glands
261
what is the role of parathyroid hormones?
Activates Vitamin D
262
What is the role of vitamin D in regards to absorption of Ca2+?
Stimulates the synthesis of calcium binding and transporting in the enterocytes e.g. calblindin and intestinal membrane calcium-binding protein
263
Give examples of dietary iron
1. Fe 3+
2. Haem
3. inorganic iron
4. Ferratin
264
Where is haem absorbed?
duodenum
265
What is the role of vitamin C in regards to Ferric iron (3+)
Acts as a reducing agent to Reduce Fe3+ to Fe2+
266
Where is gastroferrin secreted from?
gastric parietal cells.
267
What is the role of gastroferrin?
Binds to Fe2+ prevents it binding to anions thus allowing it to be absorbed.
268
Give other examples of molecules trying to promote reduction of Fe3+ to Fe2+
1. HCl within the stomach
| 2. a ferric reductase, duodenal cytochrome B (Dctyb), present on the brush border membrane of enterocytes
269
Why is Fe2+ important
Ferric (3+) cannot be absorbed only ferrous (2+) can
270
What transport protein is involved in the absoprtion of Fe2+ in the enterocytes?
DMT- Divalent metal transporter . This couples Fe2+ with H+
271
How is haem absorbed?
uncertain mechanism.
However either Haem carrier protein 1 (aka SLC48A1), or endocytosis )
272
Discuss how iron can be stored in enterocytes.
1. Fe 2+ is oxidised to Fe3+ in the cytoplasm
| 2. Binds to apoferratin to form ferratin
273
What happens once haem enters the enterocytes?
degraded by haem oxidase to form Fe2+
Biliverdin is also formed
274
What channel proteins are responsible for the efflux of Iron from enterocytes?
Mobilferrin which carried Fe2+ in cell to ferroportin
275
What is the role of Hephaestin?
Oxidises Fe2+ to Fe3+ at the basolateral surface of the enterocytes
276
What occurs to Fe3+ once it is circulating in the blood?
Binds with apotransferrin to form transferrin.
277
What increases DMT expression?
blood loss
278
What decreases DMT expression?
HFE protein
Excess body iron stores
279
What is the role of hepcidin?
Binds to ferroportin
released from liver when body iron levels are high) – major control on iron absorption
280
What is haptocorin?
It is a type of transcobalamin which binds to vitamin b12 in the stomach
It is secreted in the saliva
Pancreatic proteases break it down in the duodenum
Intrinsic factor then binds to Vitamin B12
281
What is Vitamin b12 present in?
meat,eggs ,milk- watch out vegans
282
What is Vitamin B12 used for?
methylation reactions
283
Where is folic acid absorbed?
jejunum
284
What is the role of folic acid?
methylation reactions
285
List fat soluble vitamins
A,D,E,K
286
List water soluble vitamins
B (not b12)
C
H
287
What do fat soluble vitamins rely on to be absorbed?
an adequate bile slat secretion and intact small intestinal mucosa
288
What is the function of vitamin A?
Critically important for vision
289
What is the function of Vitamin D?
Calcium homeostasis and bone formation
290
What is the function of E?
antitoxidant
291
What is the function of K?
required for post-translational modification
292
where is Vitamin A stored in the liver?
ito cells
293
Where is Vitamin D and K stored in the liver?
Hepatocytes
294
What is the difference between the absorption of fat soluble vitamins and water soluble vitamins?
Fat soluble
Incorporated into mixed micelles
Usually passively transported into enterocytes
Incorporated into chylomicrons, or VLDLs
Distributed by intestinal lymphatics
Water soluble
Transport processes in the apical membrane are similar to those described for monosaccharides, amino acids and di- and tri-peptides. May be either Na+-dependent, or Na+-independent
295
What is the function of copper?
essential co factor for oxidative enzymes
296
Where is copper stored?
In the liver bound to copper-binding proteins
297
What happens to excess copper?
excreted in bile
298
What is the role of zinc?
a co factor for many enzymes and transcription factors
299
What causes the opening fo the ileocaecal vale?
distention of the terminal ileum
300
What causes the closing of the ileocaecal valve?
distention of the caecum
301
What is the proximal colon sometimes refered to as?
the absorbing colon
302
What is the distal colon sometimes refered to as?
the storage colon
303
What are the main roles of the large intestine?
1. absorption of water and electrolytes
2. absorption of fatty acids
3. storage of colonic contents
4. periodic elimination of faeces
304
Which cells are responsible for the absorption of water and electrolytes in the large intestine?
colonocytes
305
Discuss how water and electrolytes are absorbed in large intestine
1. Atpase at basolateral surface actively switches 2 K+ for 3 Na+
2. Removal of Na+ creates conc gradient which causes Na+ to diffuse into cell similar to small intestine methods
3. efflux of Hco3- occurs at apical membrane which swaps it with chloride ions to maintain net charge
4. Also increases osmosity gradient for h20 to diffuse into cell and then into blood supply
306
What is the role of bicarbonate ions in the lumen?
The bicarbonate helps neutralize the acidic end products of bacterial action in the large intestine
307
What are the roles of the large intestine goblet cells?
secrete:
copious mucus containing glycosaminoglycans – hydrated to form a slippery surface gel
trefoil proteins involved in host defence
308
what are the effects of aldosterone on the large intestine?
aldosterone greatly enhances sodium transport capability ( increase sodium conc gradient)
309
What are the forms of movement in the large intestine?
1. Mixing ( haustration)
2. propulsion ( mass movements)
3. defaecation
310
Discuss what occurs in haustration.
Haustra are saccules which form. The shunting of these saccules is called haustra shunting. This increases the exposure of chyme to the mucosa increasing absorption of electrolytes and water.
311
What causes mass movement to occur?
gastrocolic and duodenocolic reflexes. Via Extrinsic autonomic nerves
These reflexes result from distention of the stomach and duodenum after a meal
312
Discuss what occurs in mass movement
1. constrictive ring occurs in response to a distended or irritated point in the colon
2. Then, rapidly, the 20 or more centimeters of colon distal to the constrictive ring lose their haustrations and instead contract as a unit, propelling the fecal material in this segment en masse further down the colon
pushes stool to rectum
313
What are the differences between the internal anal sphincter and the external anal sphincter?
Internal sphincter-circular smooth muscle and is involuntary
External sphincter- striated smooth muscle and is voluntary
314
which nerve supplies the external anal sphincter?
pudendal nerve
315
What triggers defecation?
Distention of the rectal wall which is triggered by faecal matter in the rectum
316
What is the role of the intrinsic myenteric defecation reflex?
after distention of rectum, afferent signals sent to myenteric plexus (ENS)
efferent signals sent to sigmoid colon to increase peristaltic waves and increase pressure in rectum
relaxes internal anal sphincter
317
What is the role of the parasympathetic defecation reflex?
Afferent signals sent to SPINAL CHORD
greatly increase the peristaltic waves in the colon. help intirinsic myenteric defecation reflex
Also relax internal anal sphincter
318
Which nerves are involved in the parasympathetic defecation reflex?
Pelvic nerves
319
What occurs if the there is prolonged distention of the rectum?
Reverse peristalsis
320
What other physiological effects occur when the defecation signals enter the spinal chords?
1. Deep breath
2. contraction of abdominal muscles
3. closure of glottis
4. pelvic floor to relax and pull outward on the anal ring
321
What are the benefits of Gut microflora?
Involved in
1. synthesis of vitamin K and B12
2. synthesis of thiamine and riboflavin
3. Breakdown of primary to secondary bile acids
4. conversion of bilirubin to non-pigmented metabolites
5. activate some drugs
6. maintain mucosal integrity
7. Intestinal immunity by competition with pathogenic microbes
322
What is flatus?
intestinal gas
323
What is eructation?
burping
324
What happens to intestinal gas?
Either absorbed in the large intestine or expelled through the anus
325
where is the myenteric plexus?
Between the circular and longitudinal layers of the intestine
326
Where is the submucosal plexus?
lies in the submucosa
327
Give examples of when the myenteric plexus is used for an inhibitory effect.
Sphincters muscles can be relaxed allowing food/chyme to move into the next stage of the GI tract
328
Give examples of ENS neurotransmitters.
1. Acetylcholine
2. Noradrenaline
3. ATP
4. serotonnin
5. CCK
6. somatostatin
7. Dopamine
329
What do voluntary nerves control in the GI tract?
1. Lips
2. Tongue
3. muscles of mastication
4. pelvic floor muscles
5. external anal sphincter
330
Where do cranial parasympathetic nerve fibres control?
Foregut and mid-gut structures
331
What do the sacral parasympathetic nerve fibres control
distal half of the large intestine and all the way to the anus
332
Where does the sacral parasympathetic nerve fibres originate from?
second, third, and fourth sacral segments of the spinal cord
333
Where are postganglionic neurons of the GI parasympathetic system normally found?
in the intrinsic plexuses
334
Where do the sympathetic fibres to the GI tract originate from?
between T5 and L2 of the spinal chords
335
What does stimulation of the sympathetic fibres normally cause in the GI tract?
Inhibits Gi tract activity
336
What are the main ways sympathetic fibres inhibit GI tract activity?
1. Inhibit smooth muscle due to secretion of noradrenaline
| 2. Inhibit the neurons of the entire ENS
337
What are the main examples which cause stimulation of sensory afferent nerves?
1. irritation of gut mucosa
2. excessive distention of the gut
3. Presence of specific chemicals in gut
338
What transmitters do afferent nerves use?
Substance P and CGRP
339
Where do visceral afferents send signals to?
Hypothalamas
340
What is the main role of parasympathetic activity in the GI tract?
Stimulates ENS
341
What does the innate defense of the GI tract include?
1. Constant movement of intestinal products
2. pH and chemical composition of intestinal secretion ( e.g. Stomach acid and bile salts)
3. Antibacterial enzymes and peptides
4. Mucins- form a tough slippery mucous gel
5. Paneth cells
6. Mast cell,s eosinophils, neutrophils,macrophages and dendritic cells in the lamina propria
342
What does the adaptive immune system of GI tract include?
1. Lamina propria lymphocytes
2. Intra-epithelial lympthocytes
3. Peyer's patches
4. Tonsils
343
What do paneth cells secrete?
defensins
344
Where are paneth cells found?
small intestine ( not in large)
345
What does saliva contain which can be used in the mucosal immune system?
Contain lysozyme
346
Where are intra-epithelial lymphocytes found?
predominantly in the small intestine.
347
What makes intra-epithelial T lympthocytes different to other lympthocytes?
1. Resident in their position and don't migrate
2. express different T cell receptor
3. React to lipid antigens present on CD1 cell surface molecule rather than peptide MHC class I or II molecules
4. special role responding to proteolipid antigens in bacterial cell membranes
348
Where are peyer's patches found?
Predominantly in the terminal ileum ( not large intestine)
349
What do peyer's patches contain?
```
macrophages
dendritic cells
intra-epithelial lymphocytes
effector T cells
IgA secreting plasma cells
innate lymphoid cells
stromal cells (eg fibroblasts)
```
350
What makes up the epithelial lining of Peyer's patches?
M cells
enterocytes
351
What does the specialised dome epithelium of the peyer's patches not contain?
Villi and crypts
352
Why are M cells specialised?
contain no Microvilli but membranous folds which enclose lymphocytes, macrophages and dendritic cells.
353
What is the function of M cells?
transport intact peptides,viruses and bacteria across epithelium via endo and exocytosis and release them via the basolateral membrane where the antigens are detected by dendritic cells
354
Where are Tonsils found?
Opening of hypopharynx
Stomach
colon
appendix
355
Why must the immune system not react to food antigens?
1. Allergies
| 2. Hypersensitivity
356
what is the usual hypersensitivity response to food?
```
vomiting
diarrhoea
pruitis
urticaria
anaphylaxis (rarely)
```
357
apart from in peyers patches, how else can antigen presentation in the gut occur?
ii. which cells are used in this?
directly across epithelium
ii. dendritic cells
358
What occurs in Mucosal homing?
1. T cells enter Peyers patches- directed in blood vessels by L selectin and CCR7
2. Become activated by dendritic cells in peyers patches
3. T cells now get drained via mesenteric lymph nodes and return to thoracic gut. Re enter bloodstream to the GI tract
4. Activated T lymphocytes express Α4β7 and CCR9 home to the lamina propria and intestinal epithelium
5. MADCAM-1 binds to the activated T lymphocytes on the endothelium of the blood vessel
6. Gut epithelial cells release chemokines for gut homing T lymphocytes to bind to in the lamina propria
359
What mediates mucosal homing?
Addressins interact with receptors on the blood vessels in the GI tract
360
once a T cell has become activated by dendritic cells from peyers patches what integrin becomes expressed?
Α4β7
361
What is the function of Α4β7 integrin molecule ?
binds MadCAM-1 ( addressin molecule)
362
once a T cell has become activated by dendritic cells from peyers patches what chemokine becomes expressed?
CCR9
363
What ligand is used for CCR9?
CCL25 - increases higher affinity by causing a conformational change
364
What do two IgA molecules form?
polymeric IgA
365
what forms when a pIgA binds to a secretor component?
Secretory dimeric immunoglobulin A
366
What is the role of sIgA?
primarily acts by blockading epithelial receptors (e.g. by binding their ligands on pathogens), by sterically hindering attachment to epithelial cells, and by immune exclusion
Basically bind and neutralise antigens and toxins
367
Where are IgA produced?
Plasma cells
368
What joins to form an immunoglobulin dimer?
J chain
369
How does sIgA get released from the mucosa?
crosses the cytoplasm (transcytosis) of the enterocyte and then released at the apical surface by proteolytic cleavage of the secretory component.
370
How do sIgA enter the enterocyte?
endocytosis
371
intraepithelial lympthocytes are CD8 positive true or false?
true
372
What is the difference between humoral intestinal response and systemic humoral response?
Opposite in proportion of the different types of immunoglobulins produced
Intestine
80% IgA
15% IgM
5% IgG
systemic
80% IgG
15% IgM
5% IgA
373
What does the lamina propria consist of in regards to the immune system? Not peyers patches
1. Mast cells
2. CD4 T cells
3. mast cell
4. dendritic cell
5. Immunoglobulin A
6. Plasma cells
374
What does the epithelium of the intestine contain in regards to the immune system? Not peyers patches
1. CD8 T lymphocyte (IEL)
| 2. Dendritic cells
375
What happens when a mucosal intestinal epithelial cell becomes infected?
Displays viral peptide to CD8 Intra epithelial lymphocyte via MHC class 1
CD8 T Lymphocycte then kills cell via perforin and fas dependent pathway
376
What do enterocytes produce when infected?
Express MIC-A and MIC-B
377
What does an Intra epithelial cell bind MIC-A and MIC-B to?
NKG2D
378
what type of spontaneous electrical activity occurs in the stomach, small intestine and large intestine?
slow wave
379
what are the pacemaker cells within the stomach, small intestine and large intestine which drive the slow wave electrical activity?
interstitial cells of Cajal
380
what has to happen for a slow wave in the stomach, small intestine and large intestine to cause an action potential?
slow wave has to meet the threshold
381
what is force of contraction of the smooth muscle within the GI tract related to?
the number of action potentials discharged
| ie the length of time that the slow wave was above threshold
382
where are interstitial cells of Cajal located?
- between longitudinal and circular muscle layers
| - submucosa
383
when does slow wave activity in the GI tract generally remain in the background and not reach thresholds?
between meals
384
what is the basic electrical rhythm (BER) of the GI tract determined by?
slow waves
385
what are the factors which determine whether a slow wave amplitude reaches threshold/for how long it remains above threshold?
neuronal stimuli
hormonal stimuli
mechanical stimuli
386
using basic electrical rhythm (BER), explain why chyme moves from oral to aboral direction within the small intestine?
higher BER in the duodenum than the terminal ileum
| more vigorous mechanical activity proximally pushes food distally in the small intestine
387
using the basic electrical rhythm (BER), explain why the colon is able to hold contents for a long period of time?
higher BER in the distal colon than the proximal colon
| more vigorous actiivty distally favours retention of luminal contents
388
what neurones is the enteric nervous system made of?
sensory neurones
interneurones
effector neurones
389
what inhibitory influences does parasympathetic supply to the GI tract have?
relaxation of some sphincters
| receptive relaxation of stomach
390
what excitatory influences does parasympathetic supply to GI tract have?
increases secretions
increases blood flow
generally increases smooth muscle contraction
391
what inhibitory influences does the sympathetic supply to the GI tract have?
decreased motility
decreased secretions
decreased blood flow
392
What is the role of the spleen?
1. Breaks down RBCs - produces bilirubin
2. Site for lymphocyte proliferation
3. breaks down platelets
4. recycles iron and globin
393
Which part of the duodenum does the pancreatic juices and bile drain into?
2nd part
394
What is the role of the hepatic portal vein?
Drains venous blood from absorptive parts of the GI tract and associated organs to the liver for cleaning
395
what are the main properties of collateral veins in portal-systemic anastomoses?
1. No valves
2. blood flows either into systemic or portal system
3. Very little blood flows within these veins
396
what is the role of the ampulla of the rectum?
holds and accumulates fecal matter.
397
What is the role of the levator ani muscles?
supports pelvic organs- tonically contracted most of the time.
Relax to allow defecation and urination ( pelvic diaphragm descends)
398
Whats causes levator ani to actively contract?
Increase in intra abdominal pressure - caused by contraction of abdominal muscles and thoracic diaphragm (coughing/sneezing)
399
What does contraction of the puborectalis muscle of the levator ani muscle do?
decreases the anorectal angle- acts like a sphincter to maintain continence
400
what stimulates the contraction of the internal sphincter?
distention of the rectum ampulla
401
What allows for the external sphincter to voluntarily contract?
internal sphincter relaxation
402
what is the normal flora of the mouth?
strep viridans
neisseria
candida ( few)
staphylococci
403
What is the normal flora of the stomach/duodenum
usually sterile
may have some candida and staphylococci
404
What is the normal flora of the jejenum
coliforms - rod shaped aerobic gram negative which majority ferment lactose and live mainly in large bowel
anaerobes- don't grow in presence of oxygen
405
What is the normal flora of the colon?
coliforms ( loads)
anaerobes ( loads)
enterococcus fecalis
406
What is the normal flora of the bile ducts?
usualy sterile
