Vascular Physiology and Pharmacology Flashcards

1
Q

what is the function of the vascular system?

A

to supply oxygenated blood and nutrients to tissues and remove waste products

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2
Q

outline how the blood travels through the heart?

A

the right ventricle pumps deoxygenated blood to the lungs, where it is oxygenated and passes into the left side of the heart, and through the aorta to the body

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3
Q

by which mechanisms is blood flow to each tissue regulated?

A

local chemicals, general neuronal and humoral mechanisms

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4
Q

what are the three layers of blood vessels?

A

connective tissue adventitia, smooth muscle layer, and endothelium

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5
Q

what is the function of valves?

A

ensures unidirectional blood flow back to the heart

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6
Q

what is the function of capillaries?

A

allow oxygen and nutrients to enter the interstitial fluid and carbon dioxide and water to enter the blood stream

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7
Q

how are lipid soluble solutes transported across capillaries?

A

through diffusion across the phospholipid bilayer

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8
Q

how are lipid-insoluble solutes transported across capillaries?

A

molecules can diffuse through endothelial pores

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9
Q

what is meant by ‘blood brain barrier’?

A

the pores in capillaries within the brain are much tighter, the brain has a separate circulation. its purpose is to maintain constant conditions in the brain

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10
Q

how has the blood brain barrier been shown experimentally?

A

acidic dyes such as trypan blue can be injected into the blood stream, all tissues except brain and spinal cord will be stained. this occurs because charged molecules cannot pass through the charged pores

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11
Q

what is the role of the lymphatic system?

A

re-uptake of plasma components from interstitial fluid

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12
Q

what are lymph vessels permeable to?

A

macromolecules and proteins

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13
Q

where does lymph drain back into the circulation?

A

via subclavian and jugular veins

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14
Q

what does oedema refer to?

A

block of lymph flow and build up of protein from capillaries in interstitial spaces

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15
Q

how is blood pressure measured?

A

1) cuff inflated to 120 mmHg - stops arterial blood flow
2) cuff pressure 80-120mmHg - Korotkoff sounds made by pulsatile blood flow through a compressed artery (systolic measurement)
30 cuff pressure: <80mmHg - artery no longer compressed, diastolic measurement

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16
Q

why is the blood pressure cuff placed on the left arm?

A

presence of the brachial artery allows measurement close to the heart

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17
Q

what measurements do systolic and diastolic pressure give?

A

systolic: force of the heart
diastolic: basal BP in the system

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18
Q

how is blood pressure affected as elasticity and diameter of the blood vessel increase?

A

there is an increase in cross sectional area and blood pressure decreases

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19
Q

how hypertension defined?

A

diastolic arterial BP greater than 90mmHg

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20
Q

what is primary hypertension?

A

when there is no apparent cause, associated risk factors include genetic pre-disposition, obesity, smoking, alcohol consumption, lack of exercise

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21
Q

what is secondary hypertension?

A

caused by renovascular disease or endocrine disease such as tumour of the adrenal gland

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22
Q

which factors regulate blood pressure?

A
  • changes in cardiac output

- peripheral mechanisms involved in the control of blood flow

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23
Q

what are the main classes of blood pressure regulation?

A
  • drugs that affect sympathetic nervous system/muscle contraction
  • endothelium/local regulation
  • renin-angiotensin system
  • changes in blood volume
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24
Q

outline neuronal control of blood pressure

A
  • detection of blood pressure by baroreceptors in the aortic arch and carotid sinus
  • baroreceptors are sensitive to stretch and stimulate sensory nerves which give output to cardiovascular control centres
25
how do changes in baroreceptor activity cause reciprocal changes in sympathetic activity?
increased baroreceptor activity = decrease in sympathetic activity decreased baroreceptor activity = increased sympathetic activity
26
what are the sites of action to block artery contraction?
- block NA release - adrenoceptor antagonism - effects on calcium
27
what is reserpine?
an adrenergic neuron blocker. works by entering the nerve via uptake 1 and binding to storage vesicles, preventing concentration and release of NA. it works peripherally and centrally, causing depression as a side effect
28
what is guanethidine?
an adrenergic neuron blocker that competes with NA after uptake. does so due to higher affinity at the pump. also blocks depolarisation-secretion coupling
29
what are A1-adrenoceptors responsible for?
arterial smooth muscle
30
what are A2-adrenoceptors responsible for?
nerve terminals
31
what are A1-adrenoceptor agonists used for?
treatment of shock or hypotension. examples: methoxamine, phenylephrine
32
what is shock?
characterised by inadequate perfusion of tissues
33
what are A1-adrenoceptor antagonists used for?
treatment of hypertension e.g. prazocin blocks noradrenaline induced artery constriction
34
what do A2-adrenoceptor agonists do?
act pre-synaptically to inhibit transmitter release: central a2 activation causes depression of sympathetic outflow in brain peripheral a2 activation causes buildup of NA in synaptic space, activates Gai and GIRK = autoinhibitory feedback
35
what is yohimbine?
a2-adrenoceptor antagonist. blocks pre-junctional a2-adrenoceptors and potentiates transmitter release from sympathetic nerves. removes autoinhibitory feedback on pre-junctional receptors
36
how does sympathetic nerve stimulation lead to artery contraction?
stim -> depolarisation of smooth muscle + activation of VG Ca2+ channels -> co-release of ATP couples through Gq to stimulate PLC
37
list the types of Calcium channel antagonists
N-type T-type L-type
38
what do N-type calcium channel antagonists do?
inhibit neurons involved in neurotransmitter release
39
what do T-type calcium channel antagonists do?
work in brain and heart, allow transient opening and brief influx of calcium
40
what do L-type calcium channel antagonists do?
work on smooth muscle, long lasting
41
what three types of L-type calcium channel blockers are used as antihypertensives? which location do each of these act?
- dihydropyridines: nifedipine - acts on smooth muscle - Phenethylalkamines: verapamil - acts on heart - benzothiazepines: diltiziem - acts on heart and smooth muscle. less selective
42
how do dihydropyridines work?
calcium channel blockers increase percentage of calcium channels in mode 0, where calcium channels cannot be opened on depolarisation
43
what are the 'modes' that L-type calcium channels can be in?
mode 0: calcium channels cannot be opened on depolarisation. normally 1% of channels mode 1: low probability of opening on depolarisation, normally 70% of channels mode 2: high probability of opening on depolarisation, normally 30%
44
what do atypical dihydropyridine calcium channel openers do?
increase the percentage of channels in mode 2
45
what is a diuretic?
drug that increases urine flow
46
what do clinically useful diuretics do and why is this useful?
increase sodium excreted in the urine, this is useful because NaCl is the main determinant of extracellular fluid
47
what is the primary effect of a diuretic?
decrease reabsorption of NaCl from filtrate from kidney. increased water loss being secondary to increased excretion of salt
48
what is the main function of the kidney?
eliminate waste products and regulate the volume, electrolyte content, and pH of the extracellular fluid
49
what are the glomerulus and tubular portion of the kidney?
glomerulus is the filtering apparatus, tubular portion reabsorbs H20 from filtrate
50
what are the descending and ascending limbs of the loop of Henle permeable to?
decending: H20 ascending: NaCl
51
what is glomerular filtration?
the process where fluid is driven from the capillaries into the tubular capsule by hydrodynamic force oppsed to the oncotic pressure of the plasma proteins. low mw plasma constituents appear in the filtrate, while albumin and larger proteins are retained in the blood
52
what occurs in the ascending limb of LoH?
ions are reabsorbed, and there is active movement of Na and Cl across the membrane, this restores ionic composition down to 300mOsm
53
how does the collecting duct produce 1200mOsm filtrate?
it is permeable to water, therefore water can diffuse by osmosis
54
what are the diuretics that target the three key places ions can be moved out of the filtrate?
1 - loop acting diuretics 2 - distal convoluted tubule diuretics 3- potassium sparing diuretics
55
where do thiazide diuretics act?
the loop, responsible for 15-25% excretion
56
what is frusemide and where does it act?
loop, acts at the thick segment of Loop of Henle. inhibits transport of NaCl out of the tubule and via the Na/k/Cl in luminal membrane
57
where does bendofluazide act?
distal convoluted tubule, inhibits Na/Cl transporter
58
what do potassium-sparing diuretics do?
allow exit of sodium but block excretion of potassium into the filtrate
59
what are osmotic diuretics?
pharmacologically inert substances such as mannitol, can be filtered from the plasma into glomerulus but are incompletely absorbed. this causes passive water reabsorption reduced by presence of increased osmolarity in the tubule. this results in increased water excretion