physiology/ pharmacology Flashcards
(146 cards)
1
Q
What is energy usually stored as?
A
primarily stored as fat
2
Q
What is energy homeostasis?
A
process whereby energy is matched to energy expenditure over time
3
Q
How do you calculate someone’s BMI?
what are the normal values?
A
BMI = weight (kg) divided by square of height up to BMI of 25 = thin or normal 25-30 = overweight 30-39= obese 40 or over = morbidly obese
4
Q
What are the major factors contributing to obesity?
A
genetics - genes that make you susceptible to being fat
environment - unmask latent tendencies to develop obesity
5
Q
Why is you are obese are you more susceptible to covid?
A
contain a lot of adipose tissue which contains the components for the virus to enter
6
Q
Why is fat important? what does it do during prolonged illness?
A
energy storage, energy buffer during prolonged illness
7
Q
Why is it sometimes difficult to lose weight?
A
your brain views the extra weight as normal and perceives dieting as a threat to the body’s survival
8
Q
How does the CNS influence energy balance and body weight? behaviour, ANS and neuroendocrine
A
behaviour - feeding and physical activity
ANS activity - regulates energy expenditure
Neuroendocrine - secretion of hormones
9
Q
where is the neural centre in the brain responsible for energy intake and body weight?
A
hypothalamus
10
Q
What is the definition of satiation, satiety and adiposity
A
sensation of fullness during a meal, period of time between termination of one meal and initiation of next , the state of being obese
11
Q
What are some satiation signals?
A
cholecystokinin = released in proportion to lipids and proteins in meal
glucagon like peptide - released in response to food ingestion
12
Q
When does ghrelin increase and decrease
A
Ghrelin - increase before meals and decrease after meals
13
Q
How is overall energy balance maintained?
A
- feedback loops: signals are sent and sensed in the hypothalamus act accordingly
14
Q
What are the two hormones that report fat status to the brain?
A
leptin = made and released from fat cells insulin = made and released form pancreatic beta cells
15
Q
How does leptin cause weight loss?
A
inhibits food intake and decreases body weight (deletion of this receptor causes obesity)
16
Q
how does the drug orlistat work?
What also needs supplemented?
A
inhibits pancreatic lipase decreasing triglyceride absorption
need to vitamin supplements along with it
17
Q
What is liraglutide used for?
A
treatment of type 2 diabetes but also causes weight loss
18
Q
what is gastric bypass surgery used for? (high level of what in diabetes)
A
produces substantial weight loss - high level of complete resolution of type 2 diabetes
19
Q
How does 2,4-dinitrophenol work?
Side effects?
A
Work on adaptive thermogenesis - increase energy expenditure
Can cause severe hyperthermia
20
Q
how is current transferred between smooth muscle cells?
How is a synchronous wave produced?
A
- electrical gap junctions
- cells are depolarised at the same time causing a synchronous wave -
21
Q
What are slow waves?
A
rhythmic patterns of membrane depolarisation that spread from cell to cell via gap junctions
22
Q
What drives slow wave electrical activity?
Where are they located?
A
interstitial cells of Cajal - located between circular and longitudinal muscle layers (in a bridge like fashion)
23
Q
When do slow waves cause contraction?
A
- slow wave amplitude is enough to reach a threshold and trigger a smooth muscle cell action potential (spike)
24
Q
What does the slow wave amplitude reaching threshold depend upon? (knock on effect)
A
depolarise muscle cells rather than influence slow waves directly - ie shifts slow wave peak to threshold
25
What is peristalsis?
peristalsis (wave of relaxation followed by contraction that proceeds a short distance along the gut
26
What is segmentation in the GI tract?
| where does it occur?
- (mixing) - rhythmic contractions of the circular muscle layer that mix and divide luminal contents
- occurs in the small intestine
27
colonic mass movement ?
powerful sweeping contraction that forces faeces into rectum
28
What are sphincters?
one way valves by maintaining a positive resting pressure
29
What is the role of upper O sphincter, lower O, pyloric, ileocaecal
skeletal muscle - relaxes to allow swallowing and closes during inspiration
relaxes to allow entry of food, closed to prevent reflux
regulates gastric emptying, prevents duodenal gastric reflux
regulates flow from ileum to caecum
30
Why is the stomach important in the GI system?
how does it produce chyme?
Starting point for digestion of proteins (pepsin and HCL) and continues carbohydrate digestion (salivary amylase)
mixes food with gastric secretions to produce chyme
31
What are the two types of mechanical activity of the stomach? Orad and caudad
orad stomach - tonic (maintained) minimal mixing for amylase to work
caudad stomach - phasic (intermittent, slow waves - pump propels contents towards the pylorus
32
What is retropulsion of the caudad region?
velocity of contraction overtakes movement of chyme so it rebounds the food away from the antram to ensure proper mixing ensues
33
What are the gastric factors that determine the emptying of stomach?
Rate of emptying is proportional to volume of chyme in stomach:
34
What are the duodenal factors that determine the emptying of stomach?
neuronal response - decreased antral activity (enterogastric activity)
35
List some gastric secretions in the oxyntic mucosa (fundus and body) - HCL, pepsinogen and histamine - detail what they do
HCL - activates pepsinogen to pepsin and denatures proteins
Pepsinogen - inactive precursor to pepsin
histamine - stimulates HCL secretion
36
List some pyloric gland gastric secretions (gastrin, somatostatin)
Gastrin - stimulates HCL
| somatostatin - inhibits HCL secretion
37
What is assimilation?
overall process of digestion and absorption
38
What is the definition of absorption?
absorbable products of digestion are transferred across both the apical and basolateral membranes of enterocytes
39
What are enterocytes
absorptive cells in the intestinal epithelium
40
What form must all dietary carbohydrates be in for absorption?
In the form of monosaccharides
41
What is produced when lactase is broken down?
breaks is down into glucose and galactose
42
Why is lactase rate limiting in assimilation?
The hydrolysis reactions dont occur at a faster rate than subsequent transport of the monomers produced
43
Where does the absorption of the monosaccharides take place? - What are glucose and galactose secondary active transport mediated by?
and how do they move across the membrane?
occurs in the duodenum and the jejunum
Glucose and galactose are absorbed by secondary active transport mediated by SGLT1
fructose by facilitated diffusion by GLUT2
44
How do the monosaccharides exit?
mediated by facilitated diffusion by glut2
45
How does the SGLT1 operate?
sodium binds to the channel which increases its affinity for glucose which means it is transported more readily
46
What is an example of a protein degradation reaction in order to release amino acids into the blood
Protein - peptides - amino acids - amino acids in enterocyte and then the amino acid gets released into the blood
47
Detail the process of the digestion of proteins in the stomach
HCL denatures proteins, pepsin cleaves proteins into peptides
48
How does digestion in the duodenum occur?
Five pancreatic proteases are secreted as pro enzymes from acing cells and converted to active form in the duodenum
49
Why are brush border peptidases numerous?
Each enzyme attacks a limited number of peptide bonds and oligopeptides have an extremely varied structure
50
How are amino acids transported out of enterocytes
brush border - sodium and non sodium dependant transporter
basolateral membrane - sodium dependant and independent transporters
51
How do di, tri and tetra peptides get absorbed?
via H+ dependant mechanism at brush border -
52
What is the role of the small intestine and what are the three parts of it?
Role = major site for digestion and absorption
| three parts - duodenum, jejunum and ileum
53
What does the small intestine receive?
chyme from the stomach, pancreatic juice and bile from liver and gall bladder
54
What does motility cause in the small intestine?
Mixing of the chyme with digestive juices (segmentation), slow propulsion of the chyme (peristalsis) and removal of undigested residues (migrating motor complex)
55
How is segmentation initiaited
small intestine pacemaker cells causing the basal electrical rhythm
56
How is segmentation altered?
slowed down to allow time for absorption, strength is enhanced and decreased by parasympathetic activity
57
What is the migrating motor complex?
Strong peristaltic contraction slowly passing length of the intestine which clears stomach of debris, mucus and dead epithelial cells
58
What is the MMC inhibited by?
feeding and vagal activity - gastrin and CCK
59
What is the function of secreting gastrin?
stimulates hydrogen ion secretion and stimulates growth of gastric mucosa
60
Secretin?
promotes secretion of pancreatic and biliary HCO3-
61
Cholecystokinin?
inhibits gastric emptying, causes secretion of enzymes required for digestion, ejection of bile
62
Why are gastric inhibitory peptides released?
stimulates release of insulin from pancreatic beta cells - inhibits gastric emptying
63
Motilin?
Initiates MMC
64
Ghrelin
stimulates appetite
65
What are all peptide hormones?
they all act of G coupled receptors
66
What are the juices called that the small intestine produces?
Succus entericus
67
In the pancreas - What do the exocrine and endocrine parts secrete?
endocrine (islets of langerhans) - insulin, glucagon (to blood)
exocrine - digestive enzymes from acing cells, aqueous NaHCO3-, secreted to the duodenum collectively as pancreatic juice which neutralises acidic chyme entering the duodenum
68
How is bicarbonate secreted?
co2 diffuses into cell and combines with water to form carbonic anhydrase, this then converted into carbonic acid which dissociates into hydrogen ions and bicarbonate which is secreted out of the cell and into the lumen
69
How is is pancreatic secretion controlled?
cephalic - vagal stimulation
| gastric - distension evokes a vasovagal reflex resulting in para stimulation
70
What do mucus cells secrete in the gastric crypt?
mucus and bicarbonate
71
Parietal cells
hydrochloric acid
72
enterochromaffin-like cells
histamine
73
G cells?
gastrin
74
D cells
somatostatin
75
chief cells?
Pepsinogen
76
How is hydrochloric acid controlled in gastric parietal cells?
carbon dioxide and water from carbonic acid (with carbonic anhydrase) which then dissociates into bicarbonate to and Hydrogen ions
Bicarb is taken out of cell and replaced with chloride which is secreted out when hydrogen ions are exchanged for potassium ions
77
What is the action of histamine?
secreted in response to acetyl choline
| increases cAMP which increase number of proton pumps = more gastric acid secreted
78
What is the action of acetylcholine in the gastric acid secretion?
Binds to muscarinic receptors, increases calcium release, increases no of proton pumps and so increases gastric acid secretion
79
How does gastrin work?
binds to CCK2 receptors, which increases calcium and increases gastric acid secretion
80
Somatostatin?
Inhibits cAMP and reduces histamine release which decreases the gastric acid secretion
81
How does the vomiting centre work in the brain
recipes signals from:
higher cortical centres repulsive sights, smells etc
Chemo receptor trigger zone sends emetic signal to vomit centre
vagal afferents send signals from gut to brainstem
5Ht, dopamine and ACh are the main neurotransmitters involved in nausea and vomiting
82
What do lipids comprise of?
triacylglycerols (fats/oils)
phospholipids
cholesterol
fatty acids
83
Why is it important that droplets are emulsified?
increased surface area for digestive enzymes to work and are stabilised with an amphiphilic molecules (lipids)
84
What must the structure of the lipid be if it is to be absorbed in the stomach?
Short and medium chain fatty acids are absorbed in stomach but long chains are not
85
Where are pancreatic lipases secreted? - in response to what?
Acinar cells of pancreas in response to CCK which stimulates bile flow
86
Where are bile salts released from? in response to what and what do they act are?
gall bladder in response to CCK and act as emulsifiers (big droplets to small)
87
What structure do bile salts have?
Hydrophillic (projects from surface of droplet)
| hydrophobic (adsorbs onto droplet)
88
What are some consequences if bile salts are not secreted?
Lipid malabsorption - steatorrhea (fat in faeces)
secondary vitamin deficiency due to inability to absorb fat soluble vitamins
89
Where are the final products of lipid digestion stored and released?
mixed micelles - as TAGs are hydrolysed they are replaced with TAGs which decrease droplet size until a mixed micelle is produced
90
How do fatty acids and monoglycerides transport between cell membranes?
passive diffusion
91
How are short and medium chain fatty acids absorbed?
diffuse through enterocyte, exit through basolateral membrane and enter villus capillaries
92
long chain
resynthesied to triglycerides in the ER and incorporated into chylomicrons
93
How is the chylomicron transported to the systemic circulation?
Carried in lymph vessels via the thoracic duct
94
How is cholesterol absorbed?
Why is ezetimibe important in cholesterol absorption?
NPC1L1 transports biliary and dietary cholesterol from the intestinal lumen into the enterocyte to facilitate cholesterol absorption.
Prevents internalisation by binding to NPC1L1 so results in absorption of cholesterol (used with statins)
95
Why is iron important?
important in the carrying of oxygen by haemoglobin
96
What does the iron balance in the body depend upon
tightly regulated absorption of iron in the duodenum
97
Where is dietary iron found?
mainly in the oxidised form (Fe3+)
98
What are the consequences if iron isn't tightly regulated?
deficiency - microcytic anemia
| excess - toxic due to accumulation
99
What is the purpose in iron absorption to have a molecular chaperone?
transport iron across the cell to the basolateral membrane
100
What state must the iron be in to be absorbed?
reduced ferrous state (fe2+) and it occurs by the oxidised state accepting an electron
101
What is the storage form of iron?
Ferratin - Fe2+
102
How is the absorption of iron controlled?
Divalent metal transporter one is increased when there is blood loss occurring
decreased expression by human haemochromatosis protein (mutations can fuck with this)
103
What are some fat soluble vitamins?
A D E and K (chylomicrons)
104
Water soluble vitamins?
B complex vitamins (folic acid eg) , C (ascorbate) and H (biotin)
105
What is the gross structure of the Large intestine?
Caecum and appendix, Colon - ascending, transverse, descending and sigmoid, rectum, anal canal and anus
106
What is the taeniae coli?
longitudinal muscle that is split into three strands - encircles the rectum and anal canal
107
When does smooth muscle become thickened at the end of the large intestine?
internal anal sphincter - surrounded by skeletal muscle of the external anal spinster
108
What is the haustra?
sac like bulges caused by the activity of the taeniae coli and circular muscle layers in colon
109
How does the ilecaecal valve work?
| what is it controlled by?
maintaining positive resting pressure, relaxing in response to distension in duodenum, contrating in response to distension in the ascending colon - controlled by vagus nerves
110
What is the appendix and when can appendicitis be triggered?
blind ended tube with lymphoid tissue connected to the distal caecum via the appendiceal orifice
appendicitis can occur when it is obstructed by a faecalith
111
Detail the primary functions of the colon
absorption of Na+, Cl- and H2O condense ileocaecal material to solid or semisolid stool
Absorption of short chain fatty acids - carbs not absorbed by small intestine is fermented by colonic flora to short chain fatty acids
Periodic elimination of faeces - (voluntary control after childhood)
112
What are faeces made up of?
water, cellulose, bacteria, bilirubin and small amounts of salt
113
What increases the surface area of the colon?
Colonic folds, crypts and microvilli
114
What is one of the main jobs of colonocytes?
mediate electrolyte absorption which drives absorption of water (osmosis)
115
What are some transporters and ion channels involved in moving electrolytes
sodium ab and potassium secretion (ions) enhanced by aldosterone
116
How does haustration work?
saccules of alternating contraction - similar to segmentation but is a much lower frequency
117
When is mass movement important?
contraction of large section of muscle in colon to propel faeces to distal parts
118
When is the defecation reflex triggered?
When faeces are propelled into the rectum
119
Detail the nerves involved in when he rectum fills with matter
Activates stretch receptors that send signals to the brain + spinal cord which brings about an urge to defacate
120
What is defective in Hirschsprung disease
the rectosphinteric reflex
121
What are the consequences of holding in or relaxaing the skeletal muscle of external anal sphincter
relaxing - straightening of anorectal angle,
contraction - delayed defection - rectal wall will gradually relax
122
Why is it good to have commensal bacteria in your colon?
increase immunity by competition with pathogenic microbes
| maintain mucosal integrity and promote motility
123
Why do we produce gas?
```
swallowed air (eructation) enters small intestine - absorbed or passed to colon,
gas that is not absorbed is expelled through the anus -
```
124
When is amitriptyline used?
for abdominal pain that is resistant to the other drugs (antispasmodic, laxatives etc)
125
describe the homeostasis of gastrin in the stomach
Gastrin promotes parietal cells to secrete acid
feedback loop controlled in a negative fashion to inhibit gastrin secretion through G cells
126
What is the definition of malabsorption?
Defective mucosal absorption
127
what are some common causes of malabsorption?
Coeliac disease, chrons disease
128
When should you suspect malabsorption?
Liver, pancreas or small bowel disease
129
What can cause easy bruising?
vitamin K deficiency or vitamin C deficiency - scurvy
130
What drives absorption of water? - does it require energy?
passive process driven by the transport of solutes from lumen into the blood stream - absorption of sodium provides the osmotic force for reabsorption of water
131
What do faeces normally contain?
normally contain 100ml of water along with 50ml of cellulose, bilirubin and bacteria
132
How does intestinal fluid and water move?
intestinal fluid - always coupled to solute movement
Water - transcellular or paracellular routes
133
Where do epithelial sodium channels occur? - what is this regulated by?
occurs in colon and is regulated by aldosterone
134
What drives the absorption of chlorine when Na+ is diffused into the cell
Net negative charge left so chlorine is repelled into the cell
135
How do hydrogen ions help with sodium absorption?
high pH in lumen due to excreted of bicarbonate so it drives the diffusion of hydrogen ions out of the cell in exchange for sodium entering the cell
136
How does the chlorine absorption occur?
It can occur passively going into the cell or through gap junctions - paracellular
137
What is important in Cl- secretion?
important in many dihorreas, CFTR channel is used to secrete chlorine onto apical membrane
138
How is the chlorine conductance mediated by CFTR?
opening of channels at apical membrane and insertion of new channels from intracellular vesicles into the membrane
139
More chloride secreted than absorbed =
secretory diarrhoea
140
If diarrhoea is present... what can it cause?
can involve small, large and intestine
dehydration, metabolic acidosis and hypokaelema
may be fatal - cholera
141
How is diarrhoea treated?
fluid and electrolyte balance
anti infective agents (if appropriate)
Use of antidiarrhoeal agents - symptomatic
142
Detail rehydration therapy involving SGLT1
sodium binds, increases affinity for glucose, then translocate from extra to intracellular, Sodium dissociates then glucose loses its affinity and dissociates. The cycle is then repeated
143
What does low albumin cause in liver failure?
low plasma volume due to low albumin so AAAS is activated and because liver cant metabolise aldosterone there is high secondary levels
144
What happens to the kidneys in liver failure?
Consequences for kidney – increased angiotensin 2, aldosterone, sympathetic nervous system and ADH results in (all vasoconstrictors) – potassium loss, sodium retention and water retention
Results in renal vasoconstrictors – renal prostaglandins(vaso dilate to protect from vasoconstrictors) – all these vasoconstrictors can lead to hepato-renal syndrome
145
What is the livers drug metabolism?
Drug - Oxidation reduction hydrolysis - conjugate
Phase 1 ^ (P450) and affected early - fat soluble drugs
Phase 2 (conjugation) - affected late
146
What is the mechanism of paracetamol toxicity in liver failure
Paracetamol toxicity – not have enough glutathione(in liver failure) – drugs have a longer half life, increased P450 in alcoholics and then can become toxic with normal doses
Alcohol can compete with paracetamol to reduce paracetamol toxicity
