GI strand Flashcards
(594 cards)
1
Q
What is the gastrointestinal tract also referred to as?
A
- digestive tract
- alimentary canal
2
Q
How long is the GI tract?
A
8-9 metres long
- pharynx - stomach = 1m
- small bowel = 6m
- large bowel = 1.5m
3
Q
What is the function of the GI tract?
A
to provide the body with a continual supply of water, electrolytes and nutrients through:
- motor function: move food along the GI tract at the appropriate rate
- digestion: secrete digestive juices
- absorption: absorb the digested food, water and various electrolytes
4
Q
What lines the abdominal cavity?
A
Parietal peritoneum
5
Q
What lines organs?
A
Visceral peritoneum
6
Q
What is the role of mesenteries?
A
- suspension of organs
- prevention of gut loops becoming tangled
- carry blood vessels, nerves and lymphatics
7
Q
Why does the peritoneum secrete fluid?
A
Provides lubrication to allow organs to move against each other without friction
8
Q
What does the coeliac artery supply?
A
- stomach
- spleen
- gall bladder
- pancreas
9
Q
What does the superior mesenteric artery supply?
A
- pancreas
- small bowel
- proximal region of the large intestine
10
Q
What does the inferior mesenteric artery supply?
A
- distal large intestine
- rectum
11
Q
Where does the majority of blood from the GI tract drain to?
A
hepatic portal vein
- carries absorbed nutrients to the liver for processing
12
Q
What are the major motor functions of the GI tract?
A
- accomplish propulsion
- mix gut contents with digestive secretions and expose to absorptive surface
- facilitate temporary storage
- prevent retrograde movement
- dispose of residues
13
Q
What generates the cyclical electrical activity of the gut?
A
Interstitial Cells of Cajal
- cyclical electrical activity is referred to as slow wave activity
14
Q
What stimulates depolarisation of muscles in the GI tract?
A
stretching
acetylcholine
parasympathetic nervous system
15
Q
From where do phasic contractions of the gut originate?
A
from these electrical
spikes, and as slow-wave frequency differs along the gut, so does the frequency of contractions (e.g. 3 per min in the stomach, 7-12 per min in the s. bowel, & 1- 12 per min. in colon)
16
Q
What causes hyper polarisation and relaxation of the gut?
A
adrenaline
sympathetic nervous system
17
Q
Where does tonic contraction of the gut originate from?
A
actin and myosin interaction
18
Q
What symptoms does oesophageal motor dysfunction lead to?
A
- heartburn
- dysphagia
- regurgitation
- chest pain
- difficulty swallowing
19
Q
What does fast gastric emptying lead to?
A
nausea, vomiting, cramps, bloating, diarrhoea, dizziness
20
Q
What does slow gastric emptying (gastric resus) lead to?
A
nausea, vomiting, bloating, tummy pain, feeling full quickly
21
Q
What symptoms does colon motor dysfunction lead to?
A
- abdominal pain
- bloating
- diarrhoea
- constipation
22
Q
What is the enteric nervous system?
A
The intrinsic nervous system of the gut
23
Q
Where is the myenteric plexus found?
A
between longitudinal and circular muscle layers
24
Q
Where is the submucosal plexus found?
A
the submucosa
25
What is the role of the myenteric plexus?
control of GI movement
- excitatory fibres: cholinergic, secreting acetylcholine
- inhibitory fibres: purinergic, secreting ATP
26
What is the role of the submucosal plexus?
control of secretion and sensory functions- receives signals from gut epithelium and stretch receptors in gut wall
27
What is the role of the parasympathetic nervous system in the gut?
- main sensory and motor control
- vagus controls the foregut and midgut
- pelvic splanchnic nerves control hindgut
28
What is the role of the sympathetic nervous system of the gut?
inhibition of gut activity
| - innervates all parts of the gut
29
What are nerves with cell bodies in the submucosal plexus stimulated by?
- irritation of gut mucosa
- excessive distension of the gut
- chemical substances in the gut
30
What percentage of vagal fibres are afferent?
80%: cell bodies in submucosa and terminate in myenteric plexus
31
What is the effect of gastrin on the gut?
- increases stomach motility
- increases lower oesophageal sphincter tone
- increases small intestine/gall bladder motility
32
What is the effect of cholecystokinin on the gut?
increases gall bladder motility
33
What is the effect of secretin on the gut?
inhibits motility
34
What is the effect of gastric inhibitory peptide on the gut?
- decreases stomach motility
| - slows emptying of stomach contents into the duodenum
35
What does reduction in parasympathetic or vagal tone lead to?
- motor dysfunction
- gut inflammation
- abdominal pain
- bloating
- altered bowel habit
36
What digestion occurs in the mouth?
carbohydrates by alpha-amylase
37
What digestion occurs in the stomach?
protein by pepsin and a small amount of fat
38
What digestion occurs in the small intestine?
carbohydrates, proteins and fats by pancreatic and epithelium enzymes
39
What is trans cellular absorption and secretion?
Through epithelial cell
40
What is the paracellular route?
Through tight junctions
41
What can cause a leaky gut?
- stress
- immune response
- changes in the gut microbiome
42
What are symptoms of a leaky gut?
- abdominal pain
- bloating
- diarrhoea
43
what are the 5 parts of the stomach
- cardia
- funds
- body
- pylorus
44
what are the 3 parts to the pylorus
pyloric antrum
pyloric canal
pyloric sphincter
45
what kind of muscles form the smooth muscle of the stomach
longitudinal muscle layer
| circular muscle layer
46
what demarcates the stomach from the duodenum
pyloric sphincter
| and overlying rugae
47
what is rugae
demarcates stomach from duodenum
allows stomach to expand
has a variety of secretory cells
48
what is the secretion and motility action of the lower oesophageal sphincter and cardia
secretes:
mucus and HCO3
motility:
prevention of reflex
entry of food
regulation of belching (burping)
49
what is the secretion and motility action of the fundus and the body of the stomach
```
secretions:
H+
intrinsic factor
mucus
HCO3
pepsinogens
lipase
```
motility:
reservoir
tonic force during emptying
50
what is the secretion and motility action of the antrum and pylorus
secretions:
mucus
HCO3
```
motility:
mixing
grinding
sieving
regulation and emptying
```
51
what are the roles of gastric motility
accepting and holding food (accommodation and relaxation) - fudus and body
churning and grinding food - antrum
emptying - antrum and pylorus
52
what stops the stomach from distending too much
parasympathetic innervation from the vagus nerve
53
what kind of innervation does accommodation of the gastric motility in the stomach require
vagal
| - stretch signals from vagal nerves allows for dilatation of stomach, allowing 1L of food into stomach
54
what defects gastric motility
different consistencies of food
| eg. liquid is allowed to pass through the pyloric sphincter but thicker material is churned more first
55
what are the 2 dumping signals
late dumping syndrome
| early dumping syndrome--> rapid gastric emptying (dizziness and palpitations)
56
in what 3 ways is gastric emptying controlled
1) size of the particles in the stomach (>1-2mm cannot pass P sphincter)
2) delivery of acids, AA and lipase sensed and so hormones CCK, secretin and GIP (gastric inhibitory peptidase), released to decrease motility
3) enteric nervous system
57
what is a gastric pit and gastric gland made from
```
gastric pit:
lamina propria
mucous cells
neck--> gastric glands:
parietal cells/ oxyntic cells
smooth muscle cell
G cell
Chief cells/peptic cells
```
58
what do parietal/oxyntic cells secrete
HCL and intrinsic factor to funds and body
59
what do G cells secrete
gastrin into bloodstream
60
where are G cells mainly found
antra/pyloric glands
61
what do chief/peptic cells secrete
pepsinogen
62
what are the 2 forms go gastrin released
G17 - mainly from antrum
| G34- mainly from duodenum
63
what other hormone is gastrin homologous with
CCK-PZ - can share the same receptors
| also known as CCK-B receptor
64
what is gastrin release stimulated by
- lumen proteins/AA
| - parasympathetic input
65
what is gastrin release inhibited by
lumen H+- NEGATIVE FEEDBACK
66
what are the main actions of gastrin on the stomach
stimulate acid secretion
| promote mucosal growth
67
what are the 2 forms of somatostatin
14 and 28 aa forms
68
what is somatostatin released by
D cells of stomach, duodenum and pancreas
69
what stimulates and inhibits somatostatin release
stimulated by lumen H+
| inhibited by ACh
70
what are the effects of somatostatin
acts on G cells to inhibit gastrin
| inhibits CCK and secretin
71
what directly and indirectly effects acid secretion of parietal cells
- direct:
gastrin and ACh stimualte
somatostatin inhibits
-Indirect:
histamine
72
what is intrinsic factor? where is it released? why is it essential
binds to cobalamin /B12 in small intestine
released from parietal cells in the stomach
essential for B12/cobalamin uptake in ileum
73
other than the secretion of pepsingogen what do parietal cells release and what are the effects of this?
ACh - stimulates parietal cells to release H+
74
what is pepsingoen released in response to from chief/peptic cells?
in response to ACh
| minor effects of secretin, CCK and gastrin
75
how is pepsinogens released and what happens to them
released as pro hormones- pepsinogens
- cleaved spontaneously at low pH
- cleaved by pepsin - autolysis
76
what is pepsin
endoprotease - cut within peptide chain rather than terminal AA
77
what is the optimum pH for pepsin and at what point are they denatured
pH 2-3 optimum
| denatured above 5-7- ie. once in small bowel
78
what are gastric lipase. what is their optimum pH
initial digestion of triglycerides
cleave outer fatty acids of triglycerides = diacyl glycerol
ph 4
79
what is ptyalin a-Amylase. what is its optimum pH and when is it denatured
initial digestion of polysaccharides
optimum ph 7
denatured at ph 4
80
how is vomit controlled
centrally controlled by area postrema = chemoreceptor trigger zone:
- vagal afferents in response to irritants in and around bowel
- pain
motion sicknesss
- drugs or toxis
- pregnancy
81
what are the consequences of vomitting
```
salavation
sweating
hyperventilation
retching (involuntary contractions of diaphragm)
displacement of cardia to thorax
emptying of gastric content
```
82
what happens during vommiting
inhibition of respiration
reflex closure of glottis and soft palate
opening of lower and upper oesphageal sphincter
stomach and pyloric sphincter relax
abdominal musvcles contract
increase in intra gastric pressure
83
name the general structure of the muscular layer of the small intestine from inner to outer layers
muscosa --> submucosa --> muscular externa --> serosa (visceral peritoneum)
84
what structures are in the submucosa
lymphatic vessels
arteries and viens
submucosal plexus
85
what structures are in the muscular externa
circular muscular layer
myenteric plexus
longitudinal muscle layer
86
what are crypts of lieberkuhn
the spaces/ crevices between each villi
87
what do crypts of lieberkuhn secrete
bicarbonate rich fluid
88
what are brush border enzymes? where are they found? what's their function?
integral membrane proteins
surfaces of intestinal microvilli
break down materials in contact with
89
what is the first stage of small bowel motility
peristalsis
90
what is peristalsis? and what are the 3 stages of muscular contraction in peristalsis
peristalsis is the waves of muscular contractions which move contents along the GI tract
3 stages:
1- circular muscular contractions - contract behind bolus while circular muscles ahead of bolus relax
2- longitudinal muscular contractions - ahead of bolus contract, shortening adjacent segments
3- wave of contraction - in circulation muscles forces bolus forward
91
what is the second stage of small bowel motility
segmentation
92
what is the happens during the segmentation stage in small bowel motility ? what's the significance of this
alternate contractions of neighbouring segments
churn and fragment the bolus mixing it with intestinal secretions
93
what is the 3rd stage of small bowel motility
migrating motor complex-MMC
94
What happens during the MMC stage of small bowel motility? how often does this occur?
when gut is empty- series of strong, slow peristaltic waves sweep down from stomach to small bowel
pyloric sphincter is relaxed = large things can pass
= help clean out the gut
happens every 90 mins
95
why is MMC of small bowel important
prevents reflex and reduces bacterial growth
96
what id the MMC of the small bowel stimulated by? what is it suppressed by
motilin - released by M cells
suppressed by feeding
97
where are the APUD cells located and what is their function
crypts of lieberkuhn
| release hormones
98
what cells do the APUD cells contain? what hormones do each of these cells secrete?
I cells --> CCK
S cells --> secretin
M cells --> motilin
G cells --> Gastrin
99
what do the pancreatic duct cells release in the small intestine
bicarbonate secretion
100
what do the goblet cells release in the small intestine
mucus secretion
101
what enzymes break down carbohydrates
- soluble amylase --> breaks internal bonds a1,4
| - short chain carbohydrates then broken down by specific brush border enzymes
102
how are glucose, galactose and fructose absorbed
glucose and galactose absorbed activity by SGLT1
fructose absorbed passively by Glut5
103
by what process are proteins broken down? where does this start and by what
proteolysis
| starts in stomach by pepsin
104
what is the protein which drives proteolysis? how is it formed
trypsin
| formed from trypsinogen becoming active by enterokinase on epithelial cells
105
what cells secrete enterokinase
crypt cells
106
what proenzymes does trypsin activate and into what?
trypsinogen into trypsin
chymotrypsinogen into chymotrypsin
proelastase into elastase
procarboxypeptidase A into carboxypeptidase A
procarboxypeptidase B into carboxypeptidase B
107
name the 3 endopepdases involved in protein digestion
trypsin
chymotrypsin
elastase
108
name the exopepetidases involved in protein digestion
the carboxypeptidases ( A and B)
109
how are small peptides mad soluble in order to diffuse across the brush border
membrane bound peptidases chop them up into AA and dipeptides
110
how are AA taken up in the kidney
by sodium linked secondary active transporters
111
how are the dipeptides taken up by cells?
by proton linked secondary active transporters
112
how is the proton gradient across cells maintained
by Na+/H+ Exchange (which depends on sodium gradient )
113
what is the first stage to fat digestion? what is the significance of this stage
bile salts break up lipid droplets
| increase SA
114
why is the amiphatic nature of bile important
allows it to interact with fatty environment and watery environment
115
what is the 2nd stage of fat digestion
pancretic lipase cleaves outside fatty acids = monoglycerdie and 2 free fatty acids
116
explain the 3rd stage of fat digestion? what happens when they are inside the cell
monoglycerides and fatty acids form a complex with bile salts which soluble them = mixed micelles = cross brush border
once inside triglycerides are resynthiesed and packaged to chylomicra which are exocytosed into intersitium
117
do chylomicra empty into the capillaries of lymphatic system
into he lymphatic system - lymphatic lacteals
118
what is happens to conjugated bile salts
actively absorbed in distal ileum and recycled
| 5% ,ost in faces
119
where is calcium reabsorbed? what kind of process is this ? what is it regulated by
reabsorbed in the duodenum
ACTIVLEY
regulated by vit D
120
name the fat soluble vitamins
AKED
| absorbed with lipids
121
how are water soluble vitamins absorbed
alongside transport proteins -usualy Na+
122
how is B12 /cobalamin absorbed
by intrinsic factor
123
where does most digestion and absorption take place
small bowel
124
what is the importance of the colon
electrolyte balance and water reabsorption
125
how are NA+ and K+ secretion in the colon controlled
aldosterone
126
what divides the liver into R and L lobes
falciform ligament
127
how many segments is the liver divided into? what are they divided by
8 segemts
| by vasculature/blood vessles
128
where does the intrahepatic and extra hepatic billary drainage drain into?
intrahepatic into common hepatic duct
extra hepatic drainage into cystic and pancreatic ducts
129
what does one acini structured pancreatic cell contain
- digestive enzyme secreting cells
- pancreatic islet - islets of langerhans
- capillary
- hormones secreting islet cells
130
what surrounds the pancreas?
many tubes: enteric, billary and vascular
131
why is it hard to operate on the pancreas
lots of blood vessels surround it
132
how is the pancreas regulated
by the neuroendocrine system
133
what nerves are involved in the neuroendocrine system of the pancreas? what are their effects
- vagus nerve --> releases acetylcholine
| - splanchnic nerve --> smooth muscle release noradrenaline and decrease AcH
134
what two cells and so hormones does the duodenum have and release?
I cells --> CCK
| S cells --> secretin
135
what's stimulates motilin release in the intestine
neural stimulus
| fasting
136
what are the 3 phases of pancreatic juice secretion
1- cephalic phase
2- gastric phase
3- intestinal phase
137
what percent of pancreatic juice secretion is the cephalic phase responsible for and what is it stimulated by? what's another thing the cephalic phase stimualtes?
20%
sight, smell, taste of food --> sends signals via vagal nerve to the pancreas --> enzyme release and decrease bicarbonate
also stimulates apetite
138
what percent of pancreatic juice secretion is the gastric phase responsible for and what is it stimulated by?
10%
continuation of the cephalic phase
rich in enzymes and decrease bicarbonate
139
what percent of pancreatic juice secretion is the intestinal phase responsible for and what is it stimulated by?
70%
produces gastric chyme - partially rich in broken down fat and protein
juices rich in bicarbonate to neutralise chyme
140
what stimulates the release of CCK
lipids and peptides in small intestine (introduction of chyme)
141
what are the 2 types of CCK receptors and what hormones are they best adapted to ?
CCK A - best for CCK
CKK B - best for gastrin
142
what are the 2 main effects of CCK
stimualtion of:
- gall bladder emptying
- pancreatic secretion
143
what mechanism switches CCK off
negative feedback loop - as pH falls levels of secretin release decrease
144
what is secretin stimulated by? what are its main effects?
stimulated by acid in small intestine
main effects:
- stimulate bicarbonate secretion by ductal cells in pancreas and liver (pancreatic and bile fluid)
- modest inhibition of gastric secretion
145
does secretion have an effect on a appetite and if so what?
yes - decreases appetite
146
why are proteases formed as inactive precursors?
they are dangerous to ells if activated in wrong place at the wrong time
147
what is a trypsin inhibitor and where is to found ?
stops activation. of trypsin
found in secretory vesicles and diluted out via exocytosis
148
name the 3 pancreatic lipases
pancreatic lipase
nonspecific esterase
prophospholipase A2
149
name the 2 nucleases
deoxyribonuclease
| ribonuclease
150
what do pancreatic ducts secrete and what is this stimulated by?
bicarbonate release
stimulated by secretin and increased by CCK (via vagus)
151
in CF what are pancreatic secretions like and why?
thick and sticky due to pancreatic failure
NB-give pancreatic enzyme supplementation
152
is bile recycled?
yes- up to 8 times a day
153
what does bile consit of?
```
bile salts
phospholipids
cholesterol
bile pigmanets
inorganic ions
```
154
where do we get bile pigments from?
breakdown of Hb to bilirubin
155
what kind of charged inorganic ions does bile contain
more anions than cations as bile ha negative charge
156
during synthesis of bile acids and salts what does conjugation do?
makes them more water soluble and less toxic
157
what are hepatocytes sandwiched between?
blood supply (hepatic and portal branch) and bile duct
158
what are canaliculus and what do they secrete ?
spaces between 2 hepocytes
secrete:
- bile acids
- conjugated bilirubin
- xenobiotics (foreign molecules)
159
what is added to bile as it moves down the bile duct? what is this process stimulated by
bicarbonate
sat
water
stimulated by secretin
160
during the fasting state, what state are the bile slats in and how is this maintained?
bile salts remain dissolved as gallbladder undergoes tonic contraction
161
how does bile back up into the gall bladder
sphincter of Oddi closed so bile backs up
162
during digestive period how is bile secreted into duodenum
strong Gallbladder contractions and relaxation of sphincter of Oddi
163
what nerves regulate Gallbladder function
vagal nerve
| splanchnic nerve
164
how is the risk of gallstones reduced
(gallbladder reabsorbs salt and water and the bile components form micelles and so meaning the fluid remains isotonic )
the net proton secretion acidifies bile reducing the risk of precipitation of Ca and other salts = reducing the risk
165
are maxillary or mandibular dental arcade on the bottom or top?
maxillary top half of mouth
| mandibular = bottom half of mouth
166
what is mastication
chewing
167
what are the muscles of mastication involved in?
closing of jaw
| slide/rock jaw from side to side
168
what are the 3 major salivary glands, from largest to smallest
parotid gland (largest)
submandibular
sublingual
169
what are the roles of saliva ?
- lubrication of mouth and food and cleaning
- facilitation of taste
- protection against acid and bacteria
- digestion
170
how does saliva lubricate the mouth?
through serous and mucus fluid
171
how does saliva protect against acid and bacteria
- antibacterial enzymes (lysozyme, IgA)
- bicarbonate
- Ca2+
172
how is saliva involved in digestion
- salivary amylase (ptyalin)
| - lingual lipase
173
how is saliva production regulated
neural control : both parasympathetic and sympathetic
174
what kind of secretion does is the parasympathetic nervous system responsible for in saliva
watery secretion
175
what kind of secretion does is the sympathetic nervous system responsible for in saliva
mucoid secretion
176
how is the parasympathic secretion of saliva controlled? what's this driven by?
by salivatory centre in the brain stem
driven by:
- local stimuli (taste and touch in mouth)
- central stimuli (smell and sight of food)
- learned reflex (pavlova dogs)
177
why is it importnant to always have a background production of saliva?
prevents glands from becoming stagnant and makes sure bacteria that runs through is spat out or swallowed- infection prevention
178
what is the 2 stage production of saliva ?
1) initial isotonic fluid containing mainly NaCl, protein and mucus
2) passes along duct = salt reabsorption and HCO3- and K+ = leads to hypotonic and alkaline fluid
179
why is flow rate importnant in production of saliva ?
decrease flow rate = decrease amount of absorption of salts
180
what is the parotid gland responsible for?
- serous secretion
- 50% of saliva
- main source of salivary amylase
181
what innervation is the parotid gland under?
- parasympathic supply via glossopharyngeal (CN VI)
| - sympathy supply from superior cervical ganglion
182
what is the submandibular gland responsible for?
serous and mucous secretion
- 45% saliva
- main source of lysozyme and lactoperoxidase
183
what innervation is the submandibular gland under?
- parasympathic supply facila nerve (CN VII)
| - sympathetic supply from superior cervical ganglion
184
what is the sublingual gland responsible for?
- mucous secretion
- 5% saliva
- main source of lingual lipase
185
what innervation is the sublingual gland under?
- parasympathetic supply of facial (CN VII)
| - sympathetic from superior cervical ganglion
186
what is ptyalin a amylase involved in and how does it work?
involved in initial digestion of polysaccharides - eg. starch
a amylases can only cute a-1,4 sites (not 1,6)
187
what pH is ptyalin a amylase denatured ? Whats its optimum
4
| optimum- 4
188
what is lingual lipase involved in and how does it work?
initial digestion of triglycerides
| - cleaves outer fattty acids of triglycerides - diacyl glycerol
189
what is the optimum pH is lingual lipase ? how is it denatured
optimum - pH4
| - stable in stomach but denatured by pancreatic proteases
190
what are papillae
taste buds
191
name the 3 types of papillae from tip of the tongue to back ?
tip:
fungiform
circumvallate
follate
192
what type of cells are taste sensors
specialised epithelial cells:
- Ion channel-based sensors
- GPCR- based sensors
193
what type of cells are odour sensors
nerve cells (part of olfactory nerve)
194
how does mucous get secreted into the oesophagus?
submucosal oesophageal glands secrete mucous
195
what is the oesophagus innervated by
oesophageal plexus
196
what are the 2 flexures in the large bowel?
hepatic flexure
| splenic flecxure
197
what are haustra in the large intestine
divides the colon into little segments along its whole length
198
what is layers is the haustra made of from outer layers to inner layers?
- muscularis externa
- submucosa
- muscularis mucosae
- intestinal gland
- mucous cells
- simple columnar epithelium
199
what is the muscularis externa of the haustra made of?
- longitudinal layer- taenia coli
| - circular layer
200
where is the ileoceacal valve?
in the terminal iluem going into the caecum
201
how does the ileoceacal valve work?
one way valve :
- periodic relaxation to allow flow
- ileal distention = opens the valve
- caecal distension = closes the valve
202
is the large bowel designed to move contents along?
no
203
what is haustration ?
slow contractions in the circular muscles to squeeze contents to and fro (like segmentation)
204
what is mass movement in the large bowel? how often does it occur
- a peristaltic wave
| - a few times a day
205
how is the large bowel regulated ?
- intrinsic activity: enteric nervous activity
- some parasympathetic control
- enteroendocrine and neurocrine influences
206
where do we get the enteroendocrine and neurocrine influences for the large bowel coming form?
cells releasing 5-HT and Peptide YY
207
what triggers a mass movement in the large bowel
gastrocolic and orthocolic reflexes
208
what is an 'ileal break'
when the presence of undigested lipid in the distal ileum and proximal part of the colon releases peptide YY and so slows gastric emptying and small bowel peristalsis =. designed to stop you eating
209
how is digestion carried out in the large colon?
by bacteria (not human enzymes)
210
what do bacetria digest in the large bowel and consequently what do thyey produce?
- fiber --> short chain fatty acids (eg. butyric acid, hyrogen and methane)
- Urea and AA --> amonia
- billirubin --> urobilingoen and stercobilins
- cysteine and methonine --> hydrogen sulphide
- conjugated bile acids --> secondary bile acids
- primary bile acids --> secondary bile acids
211
what can happen if we dont have bacteria in the large bowel to digest the foods?
weight loss
212
how are short chain fatty acids absorbed in the colon? why is it important these get digested ?
- secondary active transport with Na linked transporter
| - importnant energy source for coloncytes
213
how does salt absorption happen in the colon ?
endothelial Na channels allow trnascellular Na transport
K+ in by Na/K pump
this is followed by paracellular Cl flux
followed by water
214
what is salt absorption in the colon stimulated by?
aldosterone (controls Na/K pump in kidneys and large colon)
215
how do Ecoli and Cholera effect salt secretion in the colon ? what other bacteria works in a similar way?
increase the amount of cAMP
= increases the amount of K+ and Cl lost through the channels into the lumen
= affects Na/K pump and increases amount Na lost
= leading to diarrhoea as water follows
C.Difficile works similar but instead increases Ca2+ in cell not cAMP
216
how is K+ conc determined in the colon
by plasma K+ conc
aldosterone
cAMP
217
what is the rectosigmoid junction
a sharp angle as the sigmoid colon enters the rectum
218
does the rectum contain valves?
yes
219
what are the 2 sprinters in the anus and what muscles are they comprised of?
1- internal anal sphincter : smooth muscle
| 2- external anal sphincter : skeletal muscle
220
what is the pectinate line? where is it ?
in the anal canal
| where epithelium becomes stratified squamous : what you squeeze to defecate
221
how are we able to defecate
faeces enter rectum and pressure rises triggering the internal anal sphincter to relax and the urge to defecate , anal sampling occurs and then the external sphincter and the pelvic floor relax = open way
222
what is anal sampling
anal canal determines if the substance is solid/liquid/gas and tells your brain = you decide what to do with it
223
why does sitting or squatting facilitate the passage of faeces ?
increases the rectosigmoid angle
224
what is rectal peristalsis?
triggers colonic mass movement + raised abdominal pressure (valsalva manoeuver/ grunting) providing motive force
225
What does metabolism enable?
- extraction of energy from the environment
| - synthesis of essential carbohydrates, proteins and lipids
226
What is catabolism?
Breakdown of energy rich compounds such as carbohydrates, fats and proteins
227
What are examples of catabolic pathways?
glycolysis
proteolysis
lipolysis
glyconeogenesis
228
What is anabolism?
The synthesis of complex molecules from simpler ones. These reaction pathways require ATP
229
What are examples of anabolic pathways?
glyconeogenesis
lipogenesis
gluconeogenesis
230
What are the metabolic forms of carbohydrates?
Glucose and fructose
231
What is the storage form of carbohydrates?
Glycogen
232
How long does the store of liver glycogen last?
8-10 hours
233
What is the store of glycogen in the liver used to support?
Glucose concentration in the blood
234
What is the store of glycogen in the blood used for?
Localised energy
| - rapid, but short-lived energy storage
235
What is the metabolic form of lipids?
Free fatty acids
236
Why do fats provide a very dense energy store?
They do not bind much water and contain little oxygen
237
What is the storage form of lipids?
Triglycerides
238
Where are triglycerides stored?
Adipose tissue
239
What are the disadvantages of lipids as a metabolic fuel compared to carbohydrates?
- it takes longer to re-release the energy from lipids
| - lipids cannot be synthesised back to glucose
240
What does the liver convert lipids to during starvation?
Ketone bodies
241
Why are proteins not an ideal energy source?
- they are mainly stored as functional proteins
| - catabolism of functional proteins impairs cellular function
242
How can proteins be used as a metabolic fuel?
Most amino acids can be converted to glucose in gluconeogenesis by the liver
243
What are the 4 phases of energy metabolism?
1. Absorptive
2. Post-absorptive
3. Fasting
4. Intense exercise
244
What is the average fat storage of the body?
4000MJ
245
What is the average usable protein store of the body?
100 MJ
246
What is the average liver glycogen store of the body?
2.4 MJ
247
What is the average blood glucose level of the body?
0.16 MJ
248
What is the average daily energy need of the body?
12 MJ
249
How many molecules of ATP are produced from aerobic respiration?
36
250
How many molecules of ATP are produced from glycolysis (anaerobic respiration)? (net)
2
251
What are the 3 levels of metabolic control?
1. Hormonal
2. Substrate
3. Allosteric
252
How does insulin effect:
1. sugars?
2. glycogen?
3. proteins?
4. lipids?
1. glycolysis
2. synthesis
3. synthesis
4. synthesis
253
How does glucagon/adrenaline effect:
1. sugars?
2. glycogen?
3. proteins?
4. lipids?
1. gluconeogenesis
2. breakdown
3. breakdown
4. lipolysis
254
How does growth hormone effect:
1. sugars?
2. glycogen?
3. proteins?
4. lipids?
1. glujconeogenesis
2. synthesis
3. synthesis
4. lipolysis
255
How does cortisol effect:
1. sugars?
2. glycogen?
3. proteins?
4. lipids?
1. gluconeogenesis
2. redistribute to muscle
3. breakdown
4. redistribute to abdomen
256
How does TNF-alpha and IL-1 effect:
1. sugars?
2. glycogen?
3. proteins?
4. lipids?
1. glycolysis
2. breakdown
3. breakdown
4. breakdown
257
What is the key factor for regulating metabolism in the fed and fasted states?
Blood glucose concentration (and insulin)
258
Why do the metabolic requirements of the brain differ to elsewhere in the body?
The blood-brain barrier limit what can get across
259
What is the brain reliant on?
Plasma glucose concentration and can use ketone bodies during times of fasting or starvation
260
Why do the metabolic requirements of erythrocytes differ?
They have no mitochondria so only anaerobic respiration can occur. This is inefficient
261
Describe adipose tissue
- major site of lipid storage in the form of triglycerides (TGs)
- it is sensitive to both insulin and glucagon
- HIGH GLUCOSE: insulin promotes uptake of glucose and conversion and TGs
- LOW GLUCOSE: glucagon promotes the release of free fatty and glycerol from stored TGs
262
Describe the metabolic requirements of type 1 muscle
- highly aerobic
- adapted to prolonged, modest activity
- main energy source: fatty acids
263
Describe the metabolic requirements of type 2b muscle
- Fast twitch muscle
- Explosive performance
- Quickly fatigue
- Few mitochondria
- Rely mainly on anaerobic glycolysis with glucose coming from their glycogen store
264
Describe the metabolic requirements of type 2a muscle
- intermediate between type 1 and 2b
- contain some mitochondria
- glycogen provides energy
- at lower exercise levels, fatty acids are the main energy source
265
Describe the metabolic requirements of cardiac muscle
- highly aerobic tissue
- 40% mitochondria
- main energy source is fatty acids
- can also use lactate bodies
266
What is metabolism?
Sum of all of the chemical reactions in the body
267
Why must plasma glucose levels be tightly controlled?
to be fairly tightly controlled to avoid
damage to the brain (at low levels) or a variety of other organs (at
high levels).
268
Describe the blood supply to the liver
- portal vein 75%
| - hepatic artery 25%
269
What are the contents of the portal vein?
Blood from the small intestine, stomach, pancreas and spleen
270
What is contained in the hepatic artery?
Oxygenated blood
271
What is the blood output from the liver?
The hepatic vein
272
Where does the hepatic vein drain?
The inferior vena cava
273
Describe the internal structure of the liver
Lobular structure
Made up of specialised cells and structures including Kupffner cells, hepatocytes, sinusoid cells, bile canaliculi and bile ducts
274
How is the efficiency of exchange increased in the liver?
Blood from tea hepatic portal vein and hepatic artery mixes
275
Describe hepatocytes
- make up 60% of lung tissue
| - carry out most metabolic functions
276
Describe endothelial cells
- lining of sinusoids
| - contain fenestrations so do not form a barrier for small molecules entering hepatocytes
277
Describe Kupffer cells
- located with the sinusoidal lining - macrophages
- phagocytose bacteria and old erythrocytes
- protect the lover from gut derived bacteria
278
Describe pit cells
Natural killer cells - help protect from viruses/tumour cells
279
Describe hepatic stellate cells
- lipid-filled cells
- primary site of vitamin A storage
- control turnover o connective tissue, synthesise collagen and regulate contractibility of sinusoids
280
What are the functions of the liver?
- carbohydrate, lipid and protein metabolism
- bile formation
- detoxification of xenobiotics
- removal of internal waste
- degradation of bilirubin
- storage of glucose, iron copper and vitamin A, D, K and B12
- nitrogen metabolism
- synthesis of blood components
- detoxification (haem, drugs, alcohol)
- immunological function (pit and Kupffer cells)
281
What are bile salts formed from?
Cholesterol
282
What percentage of bile salts are recirculated?
95%
283
What reduces blood cholesterol levels?
- increasing dietary fibre
| - drugs
284
What is cholestyramine (questran)?
```
Drug that
- binds bile acids in the gut
- prevents recirculation of bile
- increases bile acid synthesis
so decreases blood cholesterol
```
285
Why may gallstones form?
If more cholesterol enters bile than can be solubilised by bile salts, precipitation of cholesterol occurs. This leads to the formation of gallstones
286
Where do gallstones become lodged?
The common bile duct
287
What are xenobiotics?
- potentially toxic and of no nutritional value
| - include drugs and food additives or toxins present in food
288
What waste products are processed by the liver?
- hormones such as insulin and GH
- bilirubin (from breakdown of erythrocytes)
- urea
289
How are xenobiotics metabolised?
- Phase 1 reactions to form the primary metabolite
(Oxidation, hydrolysis, hydroxylation or reduction)
- Phase 2 reactions to form the secondary metabolite (conjugation eg sulphation or glucuronidation)
290
Why are xenobiotics metabolised?
- To inactivate them
| - It makes molecules easier to excrete as metabolites are usually more pharmacologically inactive or hydrophilic
291
What enzymes are involved in phase 1 metabolism by the liver?
cytochrome P450 enzymes (CYP)
292
Descrive cytochrome P450 enzymes
- large family of haem proteins - mono-oxygenases
- found in smooth endoplasmic reticulum
- inducible
- there is individual variation - important in therapeutics
293
Describe phase 2 metabolism by the liver
⮚ Conjugation – addition of glucuronyl, sulphate, methyl, acetyl, glycyl groups to reactive group on molecule
⮚ Various enzymes involved
⮚ Many of these reactions occur in liver, but also lung, kidney
294
Define prodrug
A prodrug is an inactive (or less active) compound which is metabolised to produce the therapeutically active form in the body
295
Why use prodrugs?
- to improve absorption in the gut
| - to allow an alternative route of administration
296
What is an example of a prodrug?
Tamoxifen is a prodrug used in the treatment of hormone-sensitive breast cancer
It is activated to produce endoxifen, 100 x more potent than tamoxifen
297
Give an example that shows why individual variation in cytochrome P450 enzymes is important in therapeutics
- The breast cancer drug tamoxifen is activated by cytochrome P450 enzymes.
- There are different levels of 2D6 enzymes in different women meaning tamoxifen has a different efficacy in different women as the drug is differentially activated
298
Why may the use of alcohol alongside other drugs increase toxicity?
- Chronic use of alcohol induces synthesis of the cytochrome P450 enzymes
- This means that certain drugs are more greatly metabolised and so have a greater effect
299
Describe what happens in a paracetamol overdose in terms of metabolism
- paracetamol is primarily metabolised via phase 2 pathways
- a normally minor route for paracetamol metabolism becomes overwhelmed in paracetamol overdose
- depletion of glutathione allows free NAPQI to react with membranes
- this results in hepatic necrosis and liver failure
300
What is the average lifespan of an erythrocyte?
120 days
301
Where are red blood cells phagocytosed?
In the Kupffer cells of the liver, spleen and bone marrow.
302
What are the stages of haem breakdown?
Haem -> Biliverdin -> Bilirubin
303
How is bilirubin transported to the liver?
Attached to albumin
304
How is bilirubin metabolised in the liver?
- conjugation (mainly with glucuronic acid)
| - Secretion into billiard canalicular - an active process
305
How is bilirubin metabolised in the gut?
- further metabolised by bacteria in the gut to urobilinogen
| - urobilinogen is then converted to urobilin or stercobilin
306
Problems with haem metabolism can lead to...
Haemolytic anaemia (preheptaic jaundice)
307
Problems with bilirubin metabolism can lead to...
Liver damage
Gilbert's syndrome
(Intrahepatic jaundice)
308
Problems with bile secretion can lead to...
blockage - gallstones/pancreatic carcinoma
| extra hepatic jaundice
309
What is weight bias?
Discrimination based on one's weight
| - many people who are obese experience discrimination as a result
310
What diseases does obesity lead to an increased risk of?
- type 2 diabetes
- hypertension
- coronary heart disease
- certain cancers such as colon
- osteoarthritis
- depression
311
How is BMI calculated?
weight (kg) / height (m^2)
312
What is a healthy BMI?
20-25
313
In which group are obesity related deaths highest?
Men and those aged above 40
314
What percentage of the population is obese?
27-29%
315
What is another measure of weight independent of BMI?
Waist circumference
316
What has been the trend in prevalence of obesity over the last 30 years?
Increasing
317
Why is the prevalence of obesity increasing?
- obesogenic environment
- people are locked not lifestyles which is toxic for energy balance and in which the pace of technological advancement has overtaken human development
318
How did the foresight report 2007 define an obesogenic environment?
a normal response to an abnormal environment
319
What is the link between families and obesity?
Shared environment and shared genetics mean that it is common for multiple members of the same family to be classed as obese
320
How is obesity managed for those with a BMI of 25-29.9?
- general advice
| - diet, physical activity
321
How is obesity managed for those with a BMI of 25-29.9 and high waist circumference and co-morbidities?
- diet
- physical activity
- consider drugs (orlistat)
322
How is obesity managed for those with a BMI of 30-39.9?
- diet
- physical activity
- consider drugs (orlistat)
323
How is obesity managed for those with a BMI of 40 and above?
- diet
- physical activity
- consider drugs (orlistat)
- consider bariatric surgery
324
How is weight managed in practice?
- motivation established
- goals set such as 5-10% reduction of initial weight
- being realistic eg in rate of weight loss and lifetstyle and behavioural changes
325
How does obesity link to COVID-19 health risk?
```
people living with obesity are twice as
likely to be hospitalized if tested
positive for COVID-19
◼an increased susceptibility to respiratory
problems, inflammation, and
immunological disturbances
```
326
What are the social determinants of health?
- racial and ethnic discrimination
- access to healthy food
- access to health care
- location and physical environment
- socioeconomic status
- education
- social and community context
327
what 3 muscles form the anterolateral abdominal wall? what supports these anteriorly and posteriorly
external oblique
internal oblique
transervous abdominous
supported anteriorly: rectus abdominous
supported posteriorly by : quadratus lumborum
328
what sheet separates abdominal and pelvic cavity?
there is no sheet
329
at what point does the oesophagus pierce the diagphram
T10
330
what does it mean if an organ is reteroperitoneal
situated outside the peritoneum, in contact with the body wall but not fully invested in peritoneum (eg.kidneys)
331
what does it mean if an organ is intraperitoneal
suspended from the abdominal wall by double layered peritoneum/mesentery (eg. GI tract)
*in general structures that change size and shape (eg.stomach) are intraperitoneal *
332
what is a mesentery
double layered fold of peritoneum
333
during development why does the whole gut tube have a dorsal mesentery
separates the gut tube from the body wall allowing it to grow longer than the body cavity, yet while still being attached to the body wall
334
other than the gut tube what other structures have this dorsal mesentery ?
Aorta
IVC
spinal chord
sympathetic chain
335
what structures of the gut retain a mesentery after development ? what are these mesenteries called?
small intestine: the mesentery of the small intestine
| transverse colon: transverse mesocolon
336
how is the transverse mesocolon separated and what are these called?
separated by mesocolic shelf into supracolic and infracolic compartments
337
what does it mean if something is secondarily retroperitoneal? name some structures like this
it used to have a mesentery but lost it
| ascending and descending colon
338
what are the 2 sacs of the abominla cavity
greater and lesser sac
339
what is the greater sac? what is the greater sac split into
main part of peritoneal cavity
| supra and infra colic compartments
340
what is the lesser sac
recess of the peritoneal cavity between the stomach and the abdominal wall
341
how are the greater and lesser sacs connected?
epiploic foramnen (of winslow)
342
during development what structure of the gut has both ventral and dorsal mesenteries ? does it stay after devlpoment
fore gut
yes remains attached to the lesser curvature of the stomach, distal oesophagus and proximal part of the duodenum after development
343
which mesenteries do the liver and spleen develop in?
liver in the ventral mesentery
| spleen in the dorsal mesentery
344
during development how is the:
- liver attached to the ventral wall
- liver attached to the stomach
- stomach attached to the spleen
- spleen attached to the dorsal wall
- liver-->ventral wall= falciform ligament (ventral mesentery)
- stomach --> liver = lesser omentum (ventral mesentery)
- stomach--> spleen = gastrosplenic ligament (dorsal mesentery)
- spleen--> dorsal wall = lienorenal ligament (dorsal mesentery)
345
what do the dorsal and ventral mesenteries turn into after development
dorsal mesentery- greater omentum
| ventral mesentery- lesser omentum
346
what are the features of the supra colic compartment
```
falciform ligament
subphrenic recess
coronary ligaments
hepatorenal recess - Morrison's recess
lesser omentum
epiploic foramen
gastrosplenic ligament
lienorenal ligament
```
347
what are the features of the infra colic compartment
paracolic gutters
| the mesenteries
348
When is the primitive gut tube formed?
During embryonic folding
349
Describe the location of the primitive gut tube
Extends from the oropharyngeal membrane to the cloacal membrane
350
What are the three parts of the primitive gut tube?
Foregut
Midgut
Hindgut
351
What is the foregut?
Primitive gut tube from mouth to 1st half of the duodenum
352
What is the midgut?
Primitive gut tube from 2nd half of duodenum to 2/3 along transverse colon
353
What is the hindgut?
Primitive gut tube from distal 1/3 transverse colon to superior 2/3 rectum
354
At what point is the midgut continuous with the yolk sac?
The vitelline duct
355
What is the epithelial lining of the primitive gut tube derived from?
Endoderm
356
What is the smooth muscle and connective tissue of the primitive gut tube derived from?
Visceral mesoderm
357
What gives rise to the visceral and parietal mesoderm?
Visceral and parietal peritoneum
358
What suspends the primitive gut tube from the posterior abdominal wall??
The dorsal mesentry
359
What is a mesentery?
A double fold of peritoneum that encloses an organ and connects to the body wall. They carry blood supply, lymphatics and nerve supply to and from organs.
360
What is an organ surrounded by a mesentery called?
Intraperitoneal
361
What is an organ not surrounded by a mesentery called?
Retroperitoneal
362
Where is the dorsal mesentery found?
From lower oesophagus to the cloaca
363
Where is the ventral mesentery found?
From lower oesophagus to 1st part of dudenum
364
What does the ventral mesentery form?
Lesser momentum and falciform ligament
365
What do the vitelline arteries give rise to?
The arteries of the gastrointestinal tract
| - after going under remodelling ad losing their connection to the gastrointestinal tract
366
What three arteries supply the gastrointestinal tract?
Coeliac trunk - foregut
Sup. mesenteric - midgut
Inf. mesenteric - handgut
367
How is the definitive gut lumen formed?
- week 6: proliferation of endoderm derived epithelial lining occludes the gut tube
- apoptosis of the epithelium occurs over the next two weeks creating vacuoles - recanalisation
- vacuoles coalesce to fully recanalise the gut tube by week 9
- during this process the epithelium undergoes further differentiation
368
What three conditions can be caused by abnormal recanalisation?
- duplication eg cyst
- stenosis
- atresia
369
Which part of the small intestine is most commonly affected by abnormal recanalisation?
ileum
| followed by duodenum
370
What is intersuception?
Part of the gut tube folds in on itself leading to narrowing
371
What does the foregut give rise to?
The respiratory diverticulum
372
How does the foregut separate from the respiratory diverticulum?
By forming a tracheoesophageal septum - pharynx and oesophagus
373
What is an oesophageal atresia?
- displacement of the tracheoesophageal septum separates proximal and distal end of oesophagus
- prevents the foetus from swallowing amniotic fluid and returning it to the mother through the placental circulation
374
What is polyhydraminos?
the excessive accumulation of amniotic fluid — the fluid that surrounds the baby in the uterus during pregnancy
375
Why is oesophageal atresia problematic?
There is a large foetal sac due to an increased amount of amniotic fluid. This can push on baby and stop devlopment. Also, the mother's stomach can only stretch so far.
376
When does the oesophagus form?
Week 4
377
What makes up the oesophagus?
- Endodermal epithelial lining and smooth muscle from visceral mesoderm
- Skeletal muscle derived from paraxial mesoderm
378
What is a congenital hiatal hernia?
- oesophagus lengthens rapidly in week 4-7 as stomach descends into the abdomen
- insufficient elongation results in part of the stomach positioned supradiaphragmatically
- it is irreducible
379
When is the stomach developed?
Appears in week 4 as a dilation of the foregut
380
Where is the stomach suspended from?
The ventral and dorsal mesentries
381
What forms the greater curvature?
Differential growth in week 5 - the dorsal wall grows faster
382
When does the stomach undergo rotation?
Weeks 7-8
383
Describe rotation of the stomach
- 90 degree clockwise rotation around the craniocaudal axis causes the lesser curvature to move from the ventral position to the right
- Similarly the greater curvature moves from dorsal position to the left
- The vagus nerves are initially located on left and right sides of the gut tube but are also
rotated such that the left vagus trunk becomes anterior and the right becomes dorsal
- Also rotation around the ventrodorsal axis
384
What does rotation around the ventrodorsal axis mean?
- the greater curvature faces slightly caudally
| - the lesser curvature faces slightly cranially
385
What forms the lesser peritoneal sac?
Rotation of the stomach around the craniocaudal axis
386
What is the omental bursa otherwise known as?
The lesser peritoneal sac
387
What is the epiploic foreman?
Connects the greater and lesser sacs
388
How is the greater momentum formed?
• The dorsal mesentery attached to the greater curvature of the stomach and the posterior
abdominal wall continues to grow
• Reflects back on itself to form an extension of the lesser sac (omental bursa)
• Ventral and dorsal folds fuse before birth
• The posterior layer of the greater omentum also fuses with the mesentery of the
transverse colon
389
What is congenital pyloric stenosis?
Narrowing of the pyloric sphincter caused by hypertrophy of smooth muscle
390
How common is congenital pyloric stenosis?
- affects 1 in 500 births
| - more common in males than females
391
What is the complication of congenital pyloric stenosis?
Restricts gastric emptying which can lead to dilation of the stomach
392
What are signs of congenital pyloric stenosis?
- palpable pyloric mass
- projectile vomiting
- visible peristalsis
393
What is heterotopic gastric tissue?
inappropriate differentiation of the gut tube can lead to ectopic gastric tissue
394
What are the complications of heterotopic gastric tissue?
- acid production can cause inflammation and ulceration in the surrounding area
- damage can leaf to strictures due to scarring or rupture of tissue
395
How is the duodenum formed?
The duodenum elongates in week 4 resulting in a ventrally projecting C-shape
• This is then dragged to the right by the rotating stomach
• The dorsal mesentery attached to the duodenum degenerates so that the
(majority) duodenum lies against the posterior abdominal wall – secondarily
retroperitoneal
396
What are the origins of the duodenum?
proximal half is foregut, distal half is midgut. The
| boundary is distal to the entrance of the common bile duct
397
how do prostaglandin/PGE2 effect parietal cell
bind to parietal cells and activate Gi mechanisms, decreasing gastric acid secretions
398
What are the major components of the innate immune system?
- pattern recognition receptors
- antimicrobial peptides
- cells
- complement components
- cytokines
399
What are examples of pattern recognition receptors (PRR)?
- toll-like receptors (TLRs)
- NOD-like receptors (NLRs)
- Rigl-like receptors (RLRs)
- C-type lectins (CLRs)
- Scavenger receptors
400
What are examples of antimicrobial pepsins?
defensins, cathelin, protegrin, granulsyin, histatin, secretory leukoprotease inhibitor, and probiotics
401
What are examples of innate immune cells?
Macrophages, dendritic cells, NK cells, NK-T cells, neutrophils, eosinophils, mast cells, basophils, and epithelial cells
402
What are the complement components of the innate immune system?
Classic and alternative complement pathway, and proteins that bind complement components
403
What are the cytokines of the innate immune system?
Autocrine, paracrine, endocrine cytokines that mediate host defense and inflammation, as well as recruit, direct, and regulate adaptive immune responses
404
What are pattern recognition receptors?
An inclusive term for antigen recognition receptors in the innate immune system
405
What are the two groups of pattern recognition receptors?
- Cell surface and intracellular - TLRs, NLRs, RLR’s and CLR’s
- Fluid-phase soluble receptors
406
What is the role of macrophages?
Phagocytose and kill bacteria; produce antimicrobial peptides; bind (LPS); produce inflammatory cytokines
407
What is the role of plasmacytoid dendritic cells (DCs)?
Produce large amounts of interferon- (IFN-) which has antitumor and antiviral activity, and are found in T cell zones of lymphoid organs; they circulate in blood.
408
What are the roles of myeloid dendritic cells?
Interstitial DCs are strong producers of IL-12 and IL-10 and are located in T cell zones of lymphoid organs, circulate in blood, and are present in the interstices of the lung, heart, and kidney; Langerhans DCs are strong producers of IL-12; are located in T cell zones of lymph nodes, skin epithelia, and the thymic medulla; and circulate in blood
409
What is the role of natural killer cells?
Kill foreign and host cells that have low levels of MHC+ self peptides. Express NK receptors that inhibit NK function in the presence of high expression of self-MHC
410
What is the role of NK-T cells?
Lymphocytes with both T cell and NK surface markers that recognize lipid antigens of intracellular bacteria such as M. tuberculosis by CD1 molecules and kill host cells infected with intracellular bacteria.
411
What is the role of neutrophils?
Phagocytose and kill bacteria, produce antimicrobial peptides
412
What is the role of eosinophils?
Kill invading parasites
413
What is the role of mast cells and basophils?
Release TNF-, IL-6, IFN- in response to a variety of bacterial PAMPs
414
Describe the adaptive immune system of the GI tract
Evolution in response to changing
pathogen structures
– Variable regions of pathogen that MUTATE at
greater speed than humans • Central feature is UNIQUE antigen
receptor found on each lymphocyte
• In response to infection this lymphocyte
undergoes CLONAL expansion
• High degree of specificity
415
What is the estimated range of antigenic variability?
1x10^9
416
What is the role of killer or cytotoxic T lymphocytes? (CD8)
- able to kill
| - cellular immunity
417
What is the role of helper T lymphocytes?
- secrete growth factors (cytokines) which control the immune response
- help B and T lymphocytes
418
What is the role of suppressor T lymphocytes?
To damp down immune response
419
What represents the first line of immunological defence in the GI tract? Why?
GI tract mucosal surface
• Mucosal surfaces separate the external environment from the internal
sterile environment and therefore represent the first line of defence.
420
What does the gut mucosal barrier encounter?
• Harmless antigens eg food.
• Commensal bacterial flora
• Pathogenic organisms which have developed effective methods for
colonisation and invasion
421
An important role of the mucosal immune system is...
tolerance
422
The gut immune system is .... compared to the systemic immune system
functionally and anatomically different
423
The gut immune system comprises of:
Innate defences:
• Commensal bacterial flora
• Epithelial barrier
• Biochemical factors produced by epithelial cells
Specific defences:
• Lymphoid tissue associated with mucosal surfaces - [Gut associated lymphoid tissue; GALT]:
424
Define pre-biotic
Food for bacteria- induces growth of beneficial microorganism
425
Define pro-biotic
Contains live bacteria
426
Breast milk is a source of...
pre-biotics
427
How does the gut microbiome develop over time?
Breast milk -> Inulin-type fructans (prebiotic) -> Colonic fermentation -> Acidic pH -> Lactobacillus, Bifidobacteria (probiotics) -> Stimulation of intestinal host defences -> Maturation of mucosal immune system
428
What are the benefits of gut microflora?
```
Resistance to colonisation by pathogens
• Stimulate local immunity
• Oral tolerance
• Nutrition
• Epithelial cell turnover
• Intestinal motility
```
429
What are diseases of the GI tract?
- Irritable bowel syndrome
- Ulcers (helicobacter pylori)
- Extraintestinal disease - septicaemia
- Autoimmunity - reactive arthritis
- Allergy
430
What do stem cells of the epithelial bacteria differentiate into?
Enterocytes
• Goblet cells
• Enteroendocrine cells
• Paneth cells
431
Describe the epithelial barrier
Prevents penetration by microorganisms • Intestinal mucosal barrier is a single cell layer • Self-renewing system undergoing continuous renewal from
stem cells located near the base of the crypts of Lieberkhun
432
What is the role of goblet cells in the epithelial barrier?
Produce mucins to provide for
mucus layers that resist
microbial access
433
What is the role of enterocytes in the epithelial barrier?
```
Mechanical action, cilial action
creates current to remove
microbes that are poorly
adhered • Produce antimicrobial peptides
• Defensins • Cathelicidins
• Produce antimicrobial proteins
• Lysozyme, lactoferrin
```
434
What is the role of secretory IgA in the epithelial barrier?
May be of limited specificity to
| bind to microbes
435
How is the specific immune system of the gut organised?
• Aggregated follicles in Peyers Patches [lower part of small intestine;
Ileum], appendix.
• Single follicles in along length of GI tract
• Induction of immune responses
436
What is found in the Peyer's patch?
```
M-cells [microfold cells] specialised
enterocytes adapted to antigen
uptake
• Pass antigens to professional APCs
[dendritic cells]
• Dendritic cells present antigens to T
-cells and B-cells are activated
• B-cells migrate to mesenteric lymph
nodes
• Differentiated plasma cells migrate
to tissues
• Plasma cells secrete IgA
```
437
How is oral tolerance achieved?
T cells- overwhelming response to antigen is non responsive
438
What are Peyer's patches?
specialised sites of initiation of immune responses
439
why are cells more leaky as you move down the GI tract (ie. from duodenum to colon)
structure of tight junctions vary as you move down - increasing leakiness
440
What is the concentration of ATP in most cells?
6mM
441
What mass of ATP does the average human body contain?
75g
442
What is the average ATP turnover of humans?
75kg a day
443
Under aerobic conditions, what percentage of cellular ATP is produced in the mitochondria
95%
444
Describe the outer membrane of mitochondria
- smooth and freely permeable to molecules under 5000 Da
| - no ionic or electrical gradients
445
Describe the inner membrane of mitochondria
- folded into christae permeable to a small number of molecules only via specific transporters
• a very good electrical insulator, capable of maintaining large ionic and electrical
gradients
• contains more protein than lipid – respiratory enzymes, transporter proteins
446
Describe the matrix space of mitochondria
• contains wide range of enzymes – Krebs cycle, fatty acid oxidation, urea cycle
(in liver)
• high concentrations of substrates, cofactors & ions • contains mitochondrial DNA, RNA & ribosomes (these resemble bacterial
components) though few mitochondrial proteins are coded on mitochondrial
DNA
447
Describe the inter membrane space of mitochondria
* has metabolite & ion concentrations similar to cytosol
| * contains cytochrome c
448
Summarise the link reaction
Pyruvate dehydrogenase catalyses conversion to acetyl CoA
449
What causes the neurological/cardiovascular symptoms of beri-beri?
Disruption of PDH function caused by lack of thiamine
450
What causes Wernike-Korsakoff syndrome?
Lack of thiamine
451
PDH is inhibited when...
energy levels are high
452
What are the two stages of the Krebs/citric acid cycle?
1. Synthesis of 6-C compound (citrate) which then loses 2 C as CO2 to become a 4 C compound (succinylcholine CoA)
2. Oxidation of a 4 C compound to regenerate oxaloacetate and initiate another round of the cycle
453
What are the main outputs of the Krebs cycle?
- reduces coenzymes NADH & FADH2 - electron carriers
- CO2 (waste product)
- 1 GTP = 1 ATP
454
Summarise the control of the Krebs cycle
- entry of pyruvate (glucose) controlled by need for energy and availability of Acetyl CoA from fat oxidation
- Control of cycle by need for energy as monitored by ATP : ADP and NADH; NAD+ rations
455
What are the three key enzymes of the Krebs cycle?
- citrate synthase
- isocitrate dehydrogenase
- alpha-ketoglutarate dehydrogenase
456
How does the Krebs cycle act as an exchange for intermediates for other metabolic pathways?
- Amino acid carbon skeletons feed into the Krebs cycle
- A number of anabolic (synthetic) pathways use Krebs cycle intermediates as building blocks
- Synthesis of oxaloacetate from pyruvate is important in replenishing oxaloacetate if needed
457
Why do patients with type 1 diabetes synthesis ketones?
Diabetic patients cannot use glucose effectively in the absence of insulin
Glycolysis is inhibited, [pyruvate] low
Gluconeogenesis is NOT inhibited – oxaloacetate & malate being removed to form glucose
In the absence of insulin, fatty acids are mobilised from adipose tissue and oxidised to acetyl CoA – acetyl CoA levels HIGH
But lack of oxaloacetate prevents acetyl CoA from entering the Krebs cycle
So ketones are synthesised instead
458
What are the two parts of oxidative phosphorylation?
- electron transport
| - ATP synthesis
459
Summarise electron transport
```
the energy (reduction potential) of the electrons in
NADH/FADH2 is used to create a proton gradient across the inner mitochondrial membrane – OXIDATION
```
460
Summarise ATP synthesis in oxidative phosphorylation
the energy from the proton gradient is used to phosphorylate ADP to synthesise ATP – PHOSPHORYLATION
461
How does cyanide effect oxidative phosphorylation?
Blocks removal of electrons from the chain by the reduction of oxygen to water at complex IV
462
What is the energy produced when electrons are transferred between complexes?
To pump protons across the inner mitochondrial membrane creating a H+ gradient
463
Describe the transport of ATP at the inner mitochondrial membrane
ADP must be transported into the mitochondria to supply the ATPase
ADP
ATP must be transported out to other areas of the cell Antiporter in the inner mitochondrial membrane allows this exchange Phosphate is also required – its transport into the matrix requires the movement of a Pi proton out of the intermembrane space
H+
464
How many protons are required in the synthesis of 1 molecule of ATP to cross the inner mitochondrial membrane?
4
465
NADH ... cross the inner mitochondrial membrane
cannot
466
Where is NADH oxidised and reduced?
Oxidised - cytosol
| Reduced - matrix
467
What are uncouplers?
Weak acids which are soluble in the membrane
468
How do uncouplers work?
When they penetrate the inner mitochondrial membrane they diffuse freely At the inter-membrane space interface they associate with protons – driven by the relatively high [H+]
At the matrix surface they release protons – driven by relatively low [H+]
469
Uncouplers are used to generate ... in newborns
heat
| - non-shivering thermogenesis
470
How do uncouplers generate heat in newborns?
Babies possess brown adipose tissue – has more mitochondria/ different appearance to white adipose tissue
Mitochondria in brown adipose tissue contain thermogenin (uncoupling protein-1)
When core body temperature drops, sympathetic nervous system release of noradrenalin leads to increased concentrations of free fatty acids in the cytosol, which activate thermogenin
471
Why may targeting brown adipose tissue be useful therapeutically?
To promote triglyceride clearance and weight loss
472
What is DNP?
Dinitrophenol
DNP was widely available as a ‘slimming pill’ in the USA during the 1930s
However side effects including hyperthermia, tachycardia, excess sweating, blindness (due to cataracts) & fatalities led to it being withdrawn in 1938
473
what is GALT? what does it contain
gut associated lymphocyte tissue
| contains: APCs, effector cells and largest reservoir of B and T cells
474
how are the lymphoid elements organised in the gut
- organised mucosal associated lymphoid tissue ( Peters patchers)
- diffuse mucosal associated comprising widespread leukocytes (intraepithelial lymphocytes, lymphocytes in lamina propria)
475
where are intraepithelial lymphocytes found ? what do they mostly contain
between intestinal epithelial cells
| mostly contain cytotoxic T cells
476
where are lamina propria lymphocytes found ? what do they mostly contain
in loose connective tissue - under epithelium (epithelium and lamina propriety = musocsa)
T helper cells
477
what is the function of IgA's released from GALT
- neutralises viruses and toxins
- enhances non-specific defines mechanisms
- inhibits: bacterial adhesion, macromolecule absorption and inflammtory effects of other Igs
478
Why does a low level of glucose lead to unconsciousness?
Glucose is a key energy source for the brain
479
What is glycosuria?
Excess sugar in the urine. It is dangerous as it causes more water to leave in urine leading to dehydration.
480
What concentration can glucose reach in the portal vein after a meal?
20mM
481
What can the liver use to make glucose?
Glycogen, amino acids or ketone bodies from lipids
482
What glucose transporters are important in whole body metabolism?
GLUT-2 and GLUT-4
483
What are the two types of glucose transporters?
GLUT and SGLT
484
What is the difference between GLUT and SLGT transport?
- SLGT transport is an Na+ symport
| - GLUT transport is a passive process with no role for Na+
485
Describe GLUT-1
- Km: 20mM
- found in tissues, red cells, endothelium and b cells
- constitutive
486
Descrive GLUT-2
- Km: 42mM
- mobile
- found in kidney, ileum, liver and pancreatic beta cells
- high kM means low affinity
- insulin insensitive
487
Describe GLUT-4
- Km: 2-10mM
- mobile (vesicles)
- found in skeletal muscle, heart and adipocytes
- low kM means high affinity
- insulin responsive
488
Describe GLUT-3
- Km: 10mM
- apical
- found in neurons and placenta
- high-affinity
489
Describe GLUT-5
- are both apical and mobile
- wide distributed throughout tissues
- fructose sensitive
490
Describe SGLT-1
- high affinity
- apical
- found in small intestine and kidney tubules
491
Describe SGLT-2
- low affinity
- brush-border
- found in kidney proximal tubule
- have a high capacity
492
Describe beta cells of the pancreas
- mainly central
- most abundant
- secrete insulin
493
Describe alpha cells of the pancreas
- at the periphery
| - secrete glucagon
494
Describe gamma cells of the pancreas
- few in number
| - secrete somostatin
495
How is insulin secreted?
- GLUT 2 picks up glucose as it increases in the blood flowing through the pancreas
- Glucose is metabolised through glycolysis and oxidative phosphorylation to generate ATP
- ATP closes KATP channels, depolarising the membrane
- Ca2+ influx then induces exocytosis of preformed insulin from granules
- Other secretagons act to increase exocytosis
496
How is insulin processed?
- metabolism from a preprohormone occurs in the endoplasmic reticulum
- disulphide bonds are inserted in the ER to stabilise
- cleaved to give A and B chains which are linked and a C peptide in the golgi apparatus
497
What is the function of the C peptide of insulin?
Acts as a biomarker for insulin production
498
How does insulin work?
binds to a receptor kinase stimulating a signalling cascade which increases cycling of GLUT4 transporters to cell membrane and translation and expression of proteins required for glycolysis and anabolism
499
What are the effects of insulin on the liver?
- promotes glycolysis
- promotes lipogenesis
- promotes glycogenesis
- inhibits gluconeogenesis
500
How does insulin promote glycolysis in the liver?
Increased activity of PFK increases the conversion of glucose to glucose-6-phosphate
501
How does insulin promote lipogenesis in the liver?
- conversion of fatty acids through glucose metabolism (excess acetyl Co-A from glycolysis)
- synthesis and release of VLDL
502
How does insulin promote glycogenesis in the liver?
Increased activity of glycogen synthase
503
How does insulin inhibits gluconeogenesis in the liver?
inhibition of key glucagon reponsive enzymes such as fructose-1,6-bisphosphate
504
What are the effects of insulin on skeletal muscle?
- promotion of glycolysis
- promotion of lipogenesis
- promotion of glycogenesis
- promotion of protein synthesis
505
What are the effects of insulin on adipose glucose metabolism?
- promotion of lipogenesis
| - inhibition of lipolysis
506
How does insulin promote lipogenesis in the adipose tissue?
- increased expression of GLUT 4
- increased glucose uptake and glycolysis
-- Glycolysis provides key substrates for lipogenesis
Phosphoenolpyruvate as a precursor of glycerol Acetyl CoA ( malonyl CoA) for FA synthesis
- increased expression of lipoprotein lipase
507
Glucagon release is translated as a ...
preprohormone
508
Glucagon release is driven by ...
alpha cells
509
Glucagon release is antagonised by ...
glucose
510
What is the difference between processing of insulin and glucagon?
processing of glucagon results in the generation of multiple incretins depending on whether the processing occurs in the intestine or pancreas. Insulin produces the same, wherever it is processed
511
What drives secretion of glucagon? How?
Low glucose keeps ATP level in a-cells low and keeps the K+ channel open
Causes opening of Ca2+ channel
This drives exocytosis
512
What inhibits release of glucagon? How?
High glucose keeps ATP level in a-cells elevated and closes the K+ channel
Membrane depolarization and Ca2+ channel closes
Exocytosis is inhibited
513
The key driver of metabolism in exercise is ...
adrenaline
514
What is the effect of adrenaline on metabolism in the liver?
Promotes glucose production by the Cori-Cori cycle
515
What is the effect of adrenaline on metabolism in the muscle?
glycogenolysis, and glucose uptake through increased GLUT4 expression
516
What is the effect of adrenaline on metabolism in the adipose tissue?
Lipolysis and FFA release into the blood
517
What is the Cori-Cori cycle/
A metabolic pathway in which lactate produced by anaerobic glycolysis in muscles is transported to the liver and converted to glucose, which then returns to the muscles
518
What are the symptoms of diabetes mellitus?
```
Polyuria
Polydipsia
Weight loss
Blurred vision
Ketoacidosis (in type 1)
```
519
What is type 1 diabetes?
Primary defect is an inability to produce (enough) insulin
| Autoimmune disease, in which β cells are destroyed
520
What happens in type 1 diabetes?
Excess glucagon (or insulin:glucagon imbalance) leads to lipolysis and proteolysis, and gluconeogenesis and ketogenesis in the liver
521
What is type 2 diabetes?
Primary defect is an impaired cellular response to insulin (insulin resistance)
522
What may insulin resistance in type 2 diabetes be as a result of?
- receptor downgrading
| - reduced signalling
523
how can the marginal artery assist if there is a blockage in the IMA
if the IMA becomes blacked the marginal artery can provide a functional anastomosis between the midgut and hindgut
524
why is the sigmoid colon mobile
due to its mesentery - sigmoid mesocolon
525
what is a sigmoid Volvulus ? what can it lead to
where the sigmoid twists around itself
can lead to constipation, ischemia, necrosis, infarction, rupture
526
what is the physical connection between the foregut and the hindgut? does this serve any other purpose
connection between superior pancreaticoduodenal and inferior pancreaticoduodenal - they anastomose
this is not a functional anastomosis however beaucse the arteries are so narrow
527
what is the sympathetic nerve supply of the abdomen.
- greater, lesser, least splanchnic nerves
| - lumbar splanchnic nerves
528
what is the parasympathetic nerve supply of the abdomen and which part of the abdomen do they supply?
- vagus : all the way to distal transverse colon
| - pelvic splanchnic nerves (S2-S4)- to hindgut and pelvic organs
529
name the only splanchnic nerve which is of parasympathetic supply
pelvic splanchnic nerves
530
what takes the nerve innervation for the abdomen directly to target vessels and organs
autonomic plexuses(nerve networks) around the coeliac trunk, SMA, IMA
531
describe the sympathetic pathway from the spinal chord to the target organ in the thorax
pre ganglionic fibre ---> white ramus ---> grey ramus --> post ganglionic fibres : cardiac plexus
532
describe the sympathetic pathway from the spinal chord to the target organ in the abdomen
pre ganglionic ---> white ramus ---> splanchnic nerves --> prevertebral ganglion (post-ganglionic neurons)---> Target organ
533
where do pre ganglionic nerve originate from for the empathetic supply
from T1-L2
534
where are pre-vertebral sympathetic ganglia located
Coeliac trunk
SMA
LMA
(these are also the arteries they are associated with)
535
what does the prevertebral sympathetic ganglia contain
- presynaptic parasympathetic (vagal) fibres
- visceral affront fibres
- pre synaptic sympathetic (splanchnc) fibers
536
are all the autonomic plexus interconnected
yes all 3 around the coeliac artery, SMA and the IMA are
537
what are the 3 ways the ganglions travel through the SNS
- synapse at entry level- paravertebral ganglia
- pass through sympathetic trunk without synapsing - prevertebral ganglia
- ascend and descend and synapse anywhere from the spinal chord
538
which route do the sympathetic ganglions take to get to the digestive system
pass through the sympathetic trunk without synapsing - synapse at the prevertebral ganglia
539
which route do the sympathetic ganglions take to get to the cardio-pulmonary system
synapse at the entry level- the paravertebral ganglia
540
what is the prevertebral ganglia also known as and why
pre aortic ganglia as its close to the aorta
541
what are the relative lengths for the pre ganglionic and post ganglionic fibres in the SNS
pre ganglionic is short and post ganglionic is long
542
where do pre-ganglionic neutrons for the parasympathetic supple of the abdomen come from
brainstem or sacral spinal chord
543
what are the relative lengths for the pre ganglionic and post ganglionic fibres in the paraNS
long pre ganglionic and short post ganglionic fibres
544
what do they autonomic plexus join with when they extend inferiorly
- superior hypogastric plexus (at the level of aortic bifurcation)
- inferior hypogastric plexus via the hypogastric nerves
545
at what level do we get aortic bifurcation in the abdomen
L4
546
what nerves do the inferior hypogastric plexus receive
pelvic splanchnic nerves : S2-S4
547
At what vertebral level do we get the innervation of referred pain for the foregut
T6-T9
548
At what vertebral level do we get the innervation of referred pain for the midgut
T8-T12
549
At what vertebral level do we get the innervation of referred pain for the hindgut
T12-L2
550
what 'centres' in the hypothalamus control eating
hunger and satiety (feeling of fullness after a meal)
551
what is ghrelin
28 AA peptide
552
what cells is ghrelin produced by
neuroendocrine cells of stomach
| also present as neuropeptide in the brain
553
when is ghrelin released
when the stomach is empty
554
what is the action of ghrelin
orexigenic agent - stimulates appetite
555
contrast orexigenics to anorexigens
orexigenics stimulate appetite whilst anorexigens suppress hunger
556
name hormones which are anorexigens
```
CCK
insulin
GLP-1
Peptide YY
somatostatin
oxyntomodulin
```
557
what cells produce leptin
adipocytes / adipokine
558
what are the effects of leptin
central effects - potentiate insulin
559
what cells produce adiponectin
adipocytes
560
what are the effects of adiponectin
potentiate insulin
561
what certain things can inhibit leptin and insulin
inflammatory cytokines: TNF-a and IL-6
562
where are central and peripheral the signals of anorexigens sent
nucleas of solitary tract in the medulla
563
where do the anorexigen signals travel to after going to the nucleas of solitary tract in the medulla
project to the arcuate nucleas - ARC
564
what 2 areas does the ARC have
- satiety centers in the ventromedial nucleas :VMN
| - hunger centers in the lateral hypothalamic area -LHA
565
what 2 types of neurons are present in the arcuate nucleas
- anorexigenic neurons
| - orexigenic neurons
566
what do anorexigenic neurons secrete
- proopiomelanocortin (POMC)
| - and 'cocaine-amphetamine- related transcript' - CART
567
what do orexigenic neurones
secrete agouti-related peptide -AGRP and neuropeptide Y - NPY
568
what fuels are used in starvation
glucose
fatty acids
ketone bodies
amino acids
569
what do muscles use for fuel
glucose
fatty acids
ketone bodies
570
what does the kidney convert glutamine to
glucose
571
what happens in extreme starvation
- wasting of muscle
- muscle fatigue and reduced exercise capacity
- diminished respiratory capacity
- slow HR and decreased contractility
- loss of heat generating capacity
- apathy (lack of motivation)
- death from respiratory or cardiac failure or infection
572
how are eating disorders defined
voluntary/ deliberate maintenance of low dietary intake which may lead to low body weight - or 'binging and purging'
573
is there a genetic concordance to eating disorders
yes there may be some
574
what are the associated psychological and psychiatric characteristics of eating disorders
- low self esteem
- perfectionism
- desire to control their environment
- depression
- distorted body image
575
what are the hallmark signs of anorexia
- body weight more than 15% below standard
- weight load due to voluntary abstinence
- distorted body image
- morbid fear of fatness
- amenorrhoea in women
576
do people suffering from bulimia have a better look than those suffering from anorexia
yes - usually not have the drastic low body weight
577
why do mouths of bulimic patients have rotten teeth
due to purging - gastric acid can damage the teeth
578
a BMI of under what is underweight?
<18.5
579
a BMI of under what is overweight?
>30
580
can obesity be due to genetic defects
yes - a small fraction are affected this way
581
what are the effects of obesity on the musculoskeletal system
- osteoarthritis
| - lower back pain
582
what are the effects of obesity on the circulatory system
- hypertension (CHD, stroke, renal failure)
- DVT
- pulmonary embolism
583
what are the effects of obesity on the metobolic and endocrine system
- type 2 diabetes
- dyslipidaemia
- metabolic syndrime
584
what are the effects of obesity and cancer
-endometrial, breast, colon cancers
585
what are the effects of obesity on the reproductive and urological system
- stress incontinece
- men stroll abnormaliities
- PCOS
- infertility
- ED
586
what are the effects of obesity on respiratory system
sleep apnoea
587
what are the effects of obesity on the gl system and liver
NAFLD
gasto-oesphageal reflux
gall stones
588
what symptoms contribute to metabolic syndrome
- obesity
- type 2 diabetes
- hypertension
- high plasma triglycerides
- low HDL cholesterol
589
in obesity which organs does fat accumulate in
muscle
heart
liver
590
what are the 2 types of fat
ectopic and visceral fat
591
is visceral fat responsive to insulin
no
592
what does visceral fat daily produce
- non-esterified fatty acids
- pro infamtory cytokines (IL-1/6, TNF-a)
- less adiponectin
593
how do non esterfied fatty acids affect the liver
makes the liver less sensitive to insulin - impress B cell insulin release
594
how do cytokines released affect cells
produce reactive oxygen species - which can increase risk of anthroma and CVS disease
