Week 5 Flashcards
(110 cards)
1
Q
The primary purpose of the circulation is to provide ___
A
Adequate blood flow to the organs.
2
Q
The body can infer the adequacy of cardiac output by measuring ___
A
Pressure.
3
Q
Short term BP regulation, mainly ___
A
Neural, by the baroreflex.
4
Q
Baroreceptors in ___ and ___
A
Carotid sinus (highly innervated, internal carotid artery) and aortic arch.
5
Q
Mechanism of baroreceptor activation
A
Stretch due to pressure -> opening of Na+ channels -> increased firing to brainstem CV centre in medulla (pressor and depressor centres via SNS and PNS nerves).
6
Q
Baroreflex firing rate threshold may reset within ___ to ___ days!
A
1 to 2 days.
7
Q
If blood pressure is
A
Baroreceptors silenced at
8
Q
Chemoreceptors respond to very low ___
A
Very low O2, high CO2, low pH.
Stimulated at very low MAP.
9
Q
Chemoreceptors in ___ and ___
A
Carotid and aortic bodies outside arteries.
10
Q
Chemoreceptors in ___ and ___
A
Carotid and aortic bodies outside arteries.
11
Q
Population paradox of cardiovascular death and blood pressure
A
In a population - more deaths occur in large number of people at moderate risk (moderate high BP), than in small number of people at high risk (severe high BP).
Importance of reducing BP across entire population to reduce cardiovascular death.
12
Q
Ethical principles for medical students
A
Beneficence (do good), non-maleficence (do not cause harm), respect for autonomy (informed consent), respect for privacy (confidentiality) and justice (equity, fairness, non-discrimination).
13
Q
Moral confusion
A
Feeling unsure what is right to do, or not knowing how to resolve the situation.
14
Q
Moral distress
A
Feeling unable to do what you think is right, or feeling compelled to do what you think is wrong.
15
Q
Moral distress
A
Feeling unable to do what you think is right, or feeling compelled to do what you think is wrong.
16
Q
PNS ___ heart rate via ___ receptors
A
PNS decreases heart rate via muscarinic receptors.
17
Q
SNS ___ heart rate via ___ receptors
A
SNS increases heart rate via beta-adrenoceptors.
18
Q
PNS innervates ___ and ___
A
PNS innervates SA node and AV node (nodes only) and decreases rate!
19
Q
Ions in muscarinic receptor activation
A
K+
20
Q
SNS innervates ___, ___ and ___
A
SNS innervates SA node, conducting tissue and myocardial cells (node AND muscle) and increases rate and force of contraction.
21
Q
Ions in beta-adrenoceptor activation
A
Ca2+
22
Q
Atropine is a ___ receptor ___
A
Atropine is a muscarinic receptor antagonist.
23
Q
Propranolol is a ___ receptor ___
A
Propranolol is a beta-adrenoceptor (non-selective) antagonist.
24
Q
___ has a large tonic effect on RESTING HR
A
PNS has a large tonic effect on resting HR (resting system). (SNS has a relatively small tonic effect on HR - active system to increase heart rate.)
25
If all effects of ANS blocked, HR settles to approx. ___ bpm
100 bpm.
| This is due to spontaneous activity of SA node.
26
If all effects of ANS blocked, HR settles to approx. ___ bpm
100 bpm.
| This is due to spontaneous activity of SA node.
27
Mechanisms for dysrhythmia
Altered impulse generation, or altered impulse conduction, or triggered activity.
Generation: automaticity of pacemaker cells, or abnormal generation of APs at other sites (not SA node).
Conduction: conduction block (ventricles use own slower rate) or re-entry (extra beats increase rate).
Triggered activity: early or late after-depolarisation. (e.g. excess SNS activity during refractory period).
28
Mechanisms for dysrhythmia
Altered impulse generation, or altered impulse conduction, or triggered activity.
Generation: automaticity of pacemaker cells, or abnormal generation of APs at other sites (not SA node).
Conduction: conduction block (ventricles use own slower rate) or re-entry (extra beats increase rate).
Triggered activity: early or late after-depolarisation. (e.g. excess SNS activity during refractory period).
29
4 major classes of antidysrhythmics
Class 1 - Na+ channel blocker.
Class 2 - beta-adrenoceptor antagonist.
Class 3 - K+ channel block.
Class 4 - Ca2+ channel block.
30
Effect of Na+ channel blockers
Decrease phase 0 slope and peak of VENTRICULAR AP.
31
Effect of beta-adrenoceptor antagonists
Decrease rate and conduction (SA node).
32
Effect of K+ channel blockers
Delay phase 3 of ventricular AP, prolong AP.
33
Effect of Ca2+ channel blockers
Decrease rate and conduction (most effective at SA AND AV nodes).
34
Effect of Ca2+ channel blockers
Decrease rate and conduction (most effective at SA AND AV nodes).
35
Antihypertensive drug types
```
ABCD
Angiotensin system inhibitors;
Beta-adrenoceptor antagonists;
Calcium channel blockers;
Diuretics.
```
36
Angiotensin system inhibitors include ___ inhibitors and ___ antagonists
ACE inhibitors and angiotensin receptor antagonists.
37
ACE inhibitors
"Prils"
| Inhibit conversion of AngI to AngII by ACE.
38
Effects of ACE inhibitors
Reduce vascular tone.
Reduce aldosterone production.
Reduce cardiac hypertrophy.
Prevent bradykinin breakdown!!! Remember ACE is kininase II (i.e. breakdown of kinin).
39
Adverse effects of ACE inhibitors
First-dose hypotensionl.
Dry cough and loss of taste - may lead to non-compliance.
Hyperkalaemia - therefore, often prescribed with thiazide diuretic.
Acute renal failure.
Itching, rash, angioedema, foetal malformations - likely via bradykinin.
40
Contraindications of ACE inhibitors
Pregnancy, bilateral renal stenosis, angioneurotic oedema.
41
Contraindications of ACE inhibitors
Pregnancy, bilateral renal stenosis, angioneurotic oedema. (Same as angiotensin receptor antagonists.)
42
Angiotensin receptor antagonists
"Sartans"
| Inhibit angiotensin receptors. AT-1 receptors = clinically significant receptors.
43
Effects of angiotensin receptor antagonists
Reduce vasoconstriction.
Reduce aldosterone production.
Reduce cardiac hypertrophy.
Reduce sympathetic activity.
44
Adverse effects of angiotensin receptor antagonists
Hyperkalaemia - add thiazide diuretic.
| Headache and dizziness.
45
Contraindications of angiotensin receptor antagonists
Pregnancy, bilateral renal stenosis, angioneurotic oedema. (Same as ACE inhibitors).
46
Beta adrenoceptor antagonists
```
"Olols"
Vary in:
Selectivity - B1 (cardiac) and B2.
Intrinsic sympathomimetic activity - partial agonist activity.
Lipid solubility.
```
47
Effects of beta adrenoceptor antagonists
Reduce cardiac output (by reducing rate and contractility of heart).
Reduce renin release (reduce blood volume and TPR).
48
Adverse effects of beta adrenoceptor antagonists
Cold extremities - reflex alpha1-adrenoceptor constriction, and blockade of dilatory beta2-adrenoceptors.
Fatigue - beta1 blockade -> reduced cardiac response, beta2 blockade -> constriction of skeletal muscle blood vessels.
Dreams and insomnia - due to lipid solubility and CNS effects.
Bronchoconstriction - beta2 adrenoceptor blockade in smooth muscle of airways.
49
Contraindications of beta adrenoceptor antagonists
Diabetes - masks awareness of hypoglycaemia by inducing fatigue.
Asthma - may cause bronchoconstriction by blockade of beta2-adrenoceptors.
Atrioventricular block.
50
Selectivity of propranolol and timolol
Non-selective B1 and B2 adrenoceptor antagonists.
51
Selectivity of atenolol and metoprolol.
Selective B1 adrenoceptor antagonist.
52
Selectivity of pindolol.
Non-selective B1 and B2 adrenoceptor antagonist with partial agonist activity.
53
Calcium channel blockers
E.g. verapamil, diltiazem, felodipine, nifedipine.
54
Mechanism of action of calcium channel blockers
Inhibit voltage-gated L-type Ca2+ channels in myocardium and vasculature.
55
Effects of calcium channel blockers
Reduce cardiac/vascular contractility:
Verapamil - significant effects on cardiac AND vascular muscle.
Diltiazem - less pronounced effect on cardiac cells.
Reduce vascular resistance:
Dihydropyridines (felodipine and nifedipine) - vascular selective.
56
Adverse effects of calcium channel blockers
Verapamil and diltiazem - oedema, flushing, headache, BRADYCARDIA!
Dihydropyridines (felodipine and nifedipine) - oedema, flushing, headache, REFLEX TACHYCARDIA.
57
Diuretics
E.g. thiazide diuretics, hydrochlorothiazide.
58
Effects of diuretics
Inhibit Na+/Cl- contransporter in distal convoluted tubule.
Decrease Na+ and Cl- reabsorption in renal tubules.
Increase Na+ and water excretion from kidney, and K+ loss from collecting duct.
Lower blood volume and reduce blood pressure.
59
Adverse effects of diuretics
In population, K+ loss, gout, hyperglycaemia, allergic reaction.
60
Adverse effects of diuretics
In population, K+ loss, gout, hyperglycaemia, allergic reaction.
61
Other antihypertensive drugs (not part of ABCD)
Older - alpha1 and alpha2 adrenoceptor antagonists, vasodilators.
Newer - renin inhibitors.
62
Observational studies
```
Cases series/case reports
Ecological
Cross-sectional
Case-control
Cohort
```
63
Interventional studies
Clinical trials
64
Descriptive studies
Cases series/case reports
Ecological
Cross-sectional
65
Analytical studies
Case-control
Cohort
Clinical trials
66
Cross-sectional study
Sample of population selected and information obtained at one point/period in time.
Each subject contributes data ONCE.
NO follow up of subjects!
Can explore associations among variables, but weak evidence of causality.
No explicit data on temporal relations (no follow up).
Mainly descriptive outputs esp. prevalence.
67
Case control study
Comparison of PREVIOUS exposure status between cases (subject with outcome of interest) and controls (subject without outcome of interest).
68
Case control study
Comparison of PREVIOUS exposure status between cases (subject with outcome of interest) and controls (subject without outcome of interest).
Cases are matched with controls.
NO follow up of subjects!
Explicit data on temporal relationship between exposure and outcome!
Useful for RARE OUTCOMES (c.f. cohort, would need a large group and long follow up period).
Key output = ODDS RATIO.
69
The key output of a case control study is ___
ODDS RATIO - an approximation of relative risk of outcome conferred by exposure.
Cannot determine relative risk from case control studies because they are NOT longitudinal! Remember, relative risk is a comparison between two incidence measures.
70
Interpretation of odds ratio
If exposure = smoking and case = COPD, and OR = 2, interpretation is that smoking doubles the likelihood of COPD.
71
Cohort study
LONGITUDINAL, follow up of subjects.
May be prospective or retrospective.
Collect INCIDENCE data.
Comparison of outcomes between/among subgroups e.g. unexposed vs. exposed to risk factor.
Derive RELATIVE RISKS.
Explicit (and often detailed!) knowledge about the temporal relationship between exposure and outcome.
Can include multiple exposures and outcomes (c.f. only one outcome in case control studies).
72
Difference between prospective and retrospective cohort study
Prospective cohort - start at exposure and follow up to outcome.
Retrospective cohort - start at outcome and follow up.
73
Difference between prospective and retrospective cohort study
Prospective cohort - start at exposure and follow up to outcome.
Retrospective cohort - start at outcome and follow up.
74
Two main types of bias: ___ bias and ___ bias
Selection bias.
| Information bias.
75
Selection bias
Systematic difference in characteristics of people selected for study and those not selected, or those who drop in/drop out.
Cross-sectional studies are most susceptible to selection bias - because it provides descriptive outputs.
Use intention-to-treat analysis to minimise selection bias.
76
Information bias
```
Systematic difference(s) in the way information is collected between/among groups being compared.
May occur if there is variability (esp. subjectivity) in methods for collecting information e.g. recall bias (due to preconceived notions of dangers of smoking).
Use blinding, and objective assessments (if possible) to minimise information bias.
```
77
Confounding
An exposure and confounder may be associated. A link between exposure and outcome may be discovered, but this link may be due to the confounder.
Minimise confounding by randomisation, matching by confounder (stratification), multivariate analyses).
78
Three layers of heart
Epicardium (outer) - simple squamous epithelium, subepicardial connective tissue, blood vessels, fat, nervous tissue.
Myocardium - muscle cells and capillaries.
Endocardium (inner) - endothelial layer, subendocardial connective tissue, conducting tissue.
79
Three layers of heart
Epicardium (outer) - simple squamous epithelium, subepicardial connective tissue, blood vessels, fat, nervous tissue.
Myocardium - muscle cells and capillaries.
Endocardium (inner) - endothelial layer, subendocardial connective tissue, conducting tissue.
80
Morphology of cardiomyocytes
Small cells, central nuclei, form branching fibres, and joined by intercalated discs.
GAP JUNCTIONS of intercalated discs electrically couple cells - coordinate APs and contraction.
81
Conducting pathways
Gap junctions coordinate electrical activity LOCALLY only.
Separate conducting system for contraction of different chambers - Purkinje fibres!!!
Note - heart beats at rate of fastest beating cardiac muscle cells (SA node and AV node).
82
Purkinje fibres
Modified cardiac muscle cell (larger), limited contractile machinery, and full of glycogen (appear clear/empty in histological preps.).
Form bundles in SUBENDOCARDIUM!
83
Three layers of blood vessels
Internal tunica intima - contact with blood.
Middle tunica media.
External tunica adventitia - binds blood vessel to surrounding tissue.
Note - layers vary depending on vein/artery/capillary.
84
Tunica intima
SIMPLE SQUAMOUS EPITHELIUM - i.e. ENDOTHELIUM.
On basal lamina!
Supported by thin, subendothelial connective tissue layer.
85
Tunica media
Smooth muscle arranged concentrically (or helically).
Constricts the lumen - increase resistance and therefore blood pressure.
Smooth muscle secretes connective tissue which it is embedded in (collagen type III, elastin and ground substance)!
86
Tunica adventitia
Connective tissue - collagen type I, elastin and ground substance, and embedded fibroblasts.
Binds to surrounding tissue.
In large vessels - adventitia has own blood supply (vaso vasorum).
87
Elastic arteries
Close to heart - highest BP fluctuations.
BP rises during systole and is MAINTAINED DURING DIASTOLE (does not drop to zero)!
Layers of elastin in media store energy and compress blood in lumen.
PASSIVE contraction = continuous blood flow, but pulsatile.
88
Elastic arteries
Close to heart - highest BP fluctuations.
BP rises during systole and is MAINTAINED DURING DIASTOLE (does not drop to zero)!
Layers of elastin in media store energy and compress blood in lumen.
PASSIVE contraction = continuous blood flow, but pulsatile.
89
Muscular arteries
Distribute blood to tissue.
Little elastin in media.
Elastin is concentrated in internal (and external) elastic laminae.
Contractions of media regulate BP.
90
Arterioles
GREATEST contribution to changes in BP!!!
Remember - resistance inverse to fourth power of diameter.
Arterioles give rise to capillaries (exchange vessels).
91
Capillaries
Less than diameter of RBC!
Single layer of endothelium - end sealed with tight junction!!!
Basal lamina.
Sometimes associated with a pericyte (media).
Surrounded by few collagen fibres (adventitia).
92
Fenestrated capillaries
Leaky!
E.g. in pancreas, intestines, endocrine glands.
Fenestrae may be covered by "diaphragms" - 8 wedge shaped channels.
Sometimes NO diaphragm i.e. a open space (e.g. in KIDNEY!!!).
93
Venules
Blood from capillaries drains to venules.
Initially - media is pericytes, but pericytes soon replaced by smooth muscle.
There is EXCHANGE (like capillaries) and this is the site of DIAPEDESIS of leukocytes!!!
Affected by histamine and cytokines!
94
Medium to large veins
Subendothelial connective tissue is well developed.
Adventitia is enlarged, often at expense of media.
Sometimes longitudinal smooth muscle bundles in adventitia -> stiffening!
95
Lymphatic vessels
ECF leaks out of CAPILLARIES and VENULES constantly!
Removed by lymphatic vessels.
Characterised by ABSENCE OF RED CELLS (but some white cells present).
Usually collapsed in post-mortem tissue.
VALVES!
(Large lymphatic vessels are similar to veins histologically.)
96
Tunica adventitia
Connective tissue - collagen type I, elastin and ground substance, and embedded fibroblasts.
Binds to surrounding tissue.
In large vessels - adventitia has own blood supply (vaso vasorum).
Thicker in veins than in arteries!!! - Allows veins to contain larger volumes of blood.
97
Lymphatic vessels
ECF leaks out of CAPILLARIES and VENULES constantly!
Removed by lymphatic vessels.
Characterised by ABSENCE OF RED CELLS (but some white cells present).
Usually collapsed in post-mortem tissue.
VALVES!
(Large lymphatic vessels are similar to veins histologically.)
98
Blood vessel diseases
Arteriosclerosis and arteriolosclerosis - "wear and tear".
Atherosclerosis.
Aneurysms and dissection.
Thrombosis and embolism.
Effects on blood supply -> ischaemia and infarction.
99
Risk factors for blood vessel diseases
Ageing, diabetes, hypertension -> intimal damage and thickening in arteries!
Intimal response to injury = healing but with FIBROSIS, known as arteriosclerosis!!!
100
Arteriosclerosis
Due to ageing and other risk factors e.g. diabetes, hypertension.
"Wear and tear".
Arteries become stiff and may narrow.
Sequelae = impair arterial role in BP control, and may impair blood supply to downstream tissues.
101
Arteriolosclerosis
Intimal damage and thickening of ARTERIOLES.
Mechanism by - smooth muscle cells produce excessive matrix, and proteins from blood may leak across damaged endothelium.
Called HYALINE ARTERIOLOSCLEROSIS (glassy).
Sequelae = poor blood supply to tissues (ischaemia), and possibility of microaneurysms and haemorrhage.
102
Atherosclerosis
Accumulation of inflammatory, fibrotic, necrotic and fatty material in arteries.
Described as fibroinflammatory lipid plaque - atheroma!
FIBROUS CAP and NECROTIC LIPID CORE.
Slowly narrow arteries or may rupture!
103
4 steps in formation of atherosclerosis
Fatty streak formation.
Damage, inflammation, cholesterol and fibrosis.
Stable atherosclerotic plaque.
Unstable atherosclerotic plaque.
104
Fatty streak
Collections of foam cells in intima - macrophages and smooth muscle cells take up lipids.
105
Atherosclerosis
Accumulation of inflammatory, fibrotic, necrotic and fatty material in arteries.
Described as fibroinflammatory lipid plaque - atheroma!
FIBROUS CAP and NECROTIC LIPID CORE.
Slowly narrow arteries or may rupture!
If >70% stenosis of lumen -> chronic ischaemia (e.g. stable angina, peripheral vascular disease - claudication).
May lead to aneurysm - due to weakened media, risk of rupture/haemorrhage.
106
Fatty streak
Collections of foam cells in intima - macrophages and smooth muscle cells take up lipids.
Develop esp. at ostia and branch points where atherosclerotic plaques are common.
107
Microscopic features of atherosclerosis
```
Fibrous cap
Necrotic core
Foam cells
Cholesterol clefts
Inflammatory cells (mononuclear)
Calcification
Neovascularisation
Narrowed lumen
Thickened intima
Thinned media
```
108
In atherosclerosis, ___ calcification (type)
DYSTROPHIC calcification!
In areas of cell degeneration, also in TB and breast lesions. (Other type = metastatic calcification - serum calcium and phosphate too high, reach precipitation threshold and precipitate out of solution -> calcification in blood vessels, kidneys, etc.)
109
Properties of unstable plaques, prone to rupture
```
Thinner fibrous cap (or even ulceration)
Larger necrotic core
More inflammatory cells
Less than 50% stenosis!!! Likely asymptomatic c.f. stable plaques which may cause greater stenosis!
Cases series/case reports
Ecological
Cross-sectional
Prone to rupture -> acute plaque events leading to thrombosis, thromboembolism, atheroembolism.
```
110
Risk factors for atherosclerosis
Non-modifiable - age, gender, family history, genetics, existing atherosclerosis.
Modifiable - hypertension, smoking, diabetes, cholesterol, sedentary lifestyle.
