Scenario 3

Front 1

What is classed as hypertension?

Back 1

- 140/90mmHg
- 30+% of adults but age-related

Front 2

What are the Two classes?

Back 2

- 98% Primary - Essential
- 2% Secondary - Adrenal Gland Tumours / Kidney disease / Renal artery stenosis / Genetic Disorders

Front 3

Role of smooth muscle cells in blood vessels?

Back 3

Control vascular diameter

Front 4

Role of endothelial cells in blood vessels?

Back 4

Regulate smooth muscle cells in reponse to blood borne factors / angiogenesis / inhibit thrombosis

Front 5

What % of all human mortality is due to disruption of vascular structure & function?

Back 5

40%

Front 6

How are blood vessel smooth muscle cells regulated?

Back 6

- ANS
- Hormones / Local Released
- Rhythmic contractions by pacemaker cells in GI

Front 7

What layer of a typical muscular artery are vessels, nerves, collagen and fibroblasts found in?

Back 7

Tunica Adventitia

Front 8

What are the three layers of a typical muscular artery wall?

Back 8

Inner to Outer
- Tunica Intima
- Tunica Media
- Tunica Adventitia

Front 9

Which layer of the wall are smooth muscle cells found in?

Back 9

Tunica Media

Front 10

What makes up the wall of a capillary?

Back 10

- Monolayer of endothelial
- Basal Lamina
- Pericyte
- No innervation

Front 11

What makes up the layers of a vein?

Back 11

- Thin tunic media (sparse smooth muscle)
- Well Supplied with sympathetic nerves

Front 12

What name is given to the response where pressure effects vascular tone?

Back 12

Myogenic

Front 13

Similarities between smooth & striated muscle?

Back 13

- Ca2+ triggers contraction
- Contraction by X Bridge cycling

Front 14

Differences between smooth & striated muscle? (Answers in format: In smooth muscle . . .)

Back 14

- No troponin - regulation by myosin
- Smooth muscle shortens more
- X Bridge turnover Slower
- ATP consumption smaller
- Contraction graded no twitch
- Contraction can be stimulated by depolarisation

Front 15

Mechanism of Myosin - Actin Interaction?

Back 15

- Myosin light chain kinase + Calmodulin
- Active Complex phosphorylates myosin which can then enter X Bridge cycle
- Myosin phosphatase dephosphorylates myosin

Front 16

What effects formation of active phosphorylating complex in smooth muscle?

Back 16

[Ca2+]

Front 17

What are the Ca2+ sources in smooth muscle?

Back 17

- Sarcoplasmic Reticulum (IP3)
- Voltage-gated Ca2+ channels (membrane depolarisation)
- Na+ / Ca2+ receptor-gated channels (DAG)

Front 18

What does EDRF stand for & What is it released by?

Back 18

- Endothelium Derived Relaxation Factor
- Released by bradykinin, ATP, Histamine, H+, CO2, Blood flow

Front 19

What is the action of Prostacyclin & Where is it released?

Back 19

- Inhibits platelet aggregation
- Released from endothelium

Front 20

What is the action of Endothelin & Where is it released?

Back 20

- Vasoconstrictor
- Released from endothelium

Front 21

Mechanism of Vasodilating substances?

Back 21

- Binds to receptor & [Ca2+] increases
- Increases eNOS production
- eNOS (L-arginine-->NO)
- NO increases cGMP in smooth muscle decreasing [Ca2+] and causing relaxation

Front 22

Mechanism of Vasoconstricting substances?

Back 22

- Binds to receptor
- Stimulates endothelin --> smooth muscle cell causing contraction

Front 23

What does PDE do?

Back 23

- Increased cGMP causes K+ out of cell depolarising the membrane
- Also causes Ca2+ into Sarcoplasmic Reticulum and also out of the cell
- PDE (cGMP--->GMP)

Front 24

How does sildenafil cause relaxation?

Back 24

Blocks PDE5

Front 25

What is endothelium-derived hyperpolarisation?

Back 25

- Vasodilator binds to receptor increasing intra [Ca2+]
- K+ channels open and membrane hyperpolarises
- Spreads through gap junction and decreases intra [Ca2+] causing relaxation

Front 26

What is oxidative stress and which species contribute to the effect?

Back 26

- Overproduction of reactive oxygen species
- O2- radical Superoxide
- H2O2 Hydrogen Peroxide
- O2- reacts with NO o produce perioxynitrite which prevents NO mediated vasodilation

Front 27

What other line of drugs reduce oxidative stress?

Back 27

Statins

Front 28

Agonists which increase cAMP?

Back 28

- Adrenaline on Beta Receptors
- Adenosine
- Prostacyclin
- Stimulate adenylate cyclase

Front 29

What is Metabolic Hyperaemia?

Back 29

- Increased metabolism during exercise enhances production of arteriole vasodilation (K+ H+ CO2 Lactic Acid)
- Vasodilation local and Blood Flow proportional to metabolic rate

Front 30

What is Reactive Hyperaemia?

Back 30

- Local blood flow cut off metabolites accumulate and cause vasodilation

Front 31

What makes the S1 sound?

Back 31

- Initiation of V systole
- LUB

Front 32

What makes the S2 sound?

Back 32

- Closure of semilunar valves
- DUP

Front 33

What makes the S3 sound?

Back 33

- Opening of AV valves
- Rapid refilling

Front 34

What make the S4 sound?

Back 34

- Atrial Systole
- Rarely heard except when EDP Raised

Front 35

What rhythm can develop from high EDP?

Back 35

S3S4 Gallop rhythm

Front 36

What receptors contribute to sympathetic stimulation of the heart?

Back 36

β1

Front 37

What receptors contribute to parasympathetic stimulation of the heart?

Back 37

Muscarinic

Front 38

Effect of autonomic regulation of CV system?

Back 38

- SNS increases heart rate and contractility
- PNS decreases heart rate

Front 39

What receptors contribute to sympathetic stimulation of the vasculature?

Back 39

α1 (can raise TPR)

Front 40

What receptors contribute to parasympathetic stimulation of the vasculature?

Back 40

Muscarinic & NANC (non-adrenergic, non-cholinergic neurotransmission e.g. NO)

Front 41

What effect do β2 mediate?

Back 41

Vasodilation in skeletal muscle

Front 42

Which receptors does NA released by nerves affect?

Back 42

α1 & β1

Front 43

Which receptors does circulating adrenaline affect?

Back 43

α1 & β1 & β2

Front 44

Effects of A on heart & vasculature?

Back 44

- Increases rate / Contractility / Cardiac Output
- Constriction in Most arteries / Veins
- Vasodilation in Muscle / Coronary / Liver Circulations

Front 45

Where is Ang II mainly Produced?

Back 45

- Present on endothelial cell surface
- Major site of production = lung (enormous endothelium)

Front 46

What is the action of ADH / Vasopressin?

Back 46

- Decreased water excretion
- Vasoconstriction

Front 47

What are classed as Prostanoids?

Back 47

- Prostaglandins & Thromboxanes
- Vasodilators / Vasoconstrictors / Regulate Platelet Aggregation

Front 48

Which Prostanoids are Vasodilators?

Back 48

PGE2 PGI2

Front 49

Which Prostanoids are Vasoconstrictors?

Back 49

TXA2 PGF2a

Front 50

What is the action of COX?

Back 50

- Arachidonic Acid --> PGG2 (Then differentiates to vasodilators and vasoconstrictors)
- Aspirin inhibits COX

Front 51

What is the action of Bradykinin?

Back 51

- Vasodilatation
- Increased vascular permeability

Front 52

What is the action of Hisamine?

Back 52

- NO Release
- Vasodilation
- Increased Vascular permeability

Front 53

What is the function of the Circle of Willis?

Back 53

- Multiple pathways for oxygenated blood

Front 54

How does CSF prevent cerebral veins from collapsing upon standing?

Back 54

- Displaces the erebral fluid downward
- Creates negative intracranial pressure (prevents cerebral veins from collapsing)

Front 55

Structural Adaptations of Coronary circulation?

Back 55

- Formation of coronary collaterals promoted by ischaemia
- high capillary density (1 Capillary / Myocyte)

Front 56

Structural adaptations of Cutaneous circulation?

Back 56

- Shunt blood to venous plexuses to promote heat loss

Front 57

Which fibres in the skin are heat activated?

Back 57

- Cholinergic sympathetic
- Stimulate sweating and case local production of vasodilators

Front 58

Functional adaptations of skeletal muscle circulation?

Back 58

- Strong metabolic hyperaemia overrides sympathetic tone during exercise
- Blood flow can dop by 80% upon strong sympathetic stimulation

Front 59

Functional adaptations of Pulmonary circulation?

Back 59

- Hypoxic pulmonary Vasoconstriction
- Matches perfusion to ventilation
- Becomes problem with global alveolar hypoxia --> pulmonary hypertension

Front 60

How does NA contribute to venous regulation?

Back 60

- Affects splanchnic & cutaneous

Front 61

How does pulce wave vary with age?

Back 61

- Youth and Normotension - Aorta Compliant (elastic)
- Age and Hypertension - Aorta Less compliant, Sall arteries Constricted and pulse waves faster
- Reflected wave going from thick aorta to small capillaries also faster

Front 62

What is the Pulse Pressure?

Back 62

Systolic - Diastolic

Front 63

What is the mean arterial pressure?

Back 63

Diastolic + (Systolic - Diastolic)/3

Front 64

What are approximate MAP in Head / Heart / Ankle?

Back 64

60 / 90 /180

Front 65

Where are the arterial baroreceptors and where are they innervated from?

Back 65

- Carotid Sinus [IX cranial nerve] glossopharyngeal
- Aortic Arch [X cranial nerve] vagus
- Mechanoreceptors

Front 66

Where in the brain do the arterial baroreceptors feed into?

Back 66

Brain Stem: Nucleus Tractus Solitarius

Front 67

For what range are the baroreceptors most sensitive?

Back 67

80-150 mmHg

Front 68

What effect does the baroreceptor signal have?

Back 68

- Increased sympathetic drive
- decreased parasympathetic drive
- Increased HR & Contractility & CO

Front 69

What effect does syncope (fainting) have on heart rate?

Back 69

- Initial Fight or flight sympathetic increases HR
- Then profound bradycardia strong parasympathetic & vasodilation from removal of sympathetic drive

Front 70

What effect does a decreased ADH release have on diuresis?

Back 70

Increased Diuresis

Front 71

What effect does an increased ANP release have on Na+ & H2O reabsorption?

Back 71

Decreased reabsorption

Front 72

How does sympathetic nerve activity affect renin release?

Back 72

Increases renin release

Front 73

What is normal blood pressure?

Back 73

120/80

Front 74

What is EDP?

Back 74

The pressure in the ventricle at the end of diastole, measured in the left ventricle as an approximation of the end diastolic volume / preload

Front 75

What is MAP?

Back 75

The average pressure within an artery over a complete cycle of one heart beat

Front 76

What is EDV?

Back 76

- End-Diastolic Volume
- Volume of blood in right / left ventricle at end load / diastole

Front 77

What is Primary / Essential hypertension?

Back 77

- No obvious cause
- Polygenetic predisposition
- Environmental influences (high salt / stress)
- RAAS / Sympathetic overactive

Front 78

What is secondary hypertension?

Back 78

- Cause can be found
- Renal (e.g. stenosis)
- Endocrine (e.g. Birth Control / Phaeochromocytoma)

Front 79

What equation links BP CO TPR?

Back 79

BP = CO x TPR

Front 80

Which receptors does Angiotensin II Primarily act upon?

Back 80

AT1

Front 81

1st Line Anti-Hypertensive Drugs?

Back 81

Angiotensin Receptor Blockers / Ca2+ Channel Blockers / ACE Inhibitors / Thiazide-Type Diuretics

Front 82

What is the effect of β-adrenergic receptor blockers?

Back 82

- Block sympathetic stimulation of the heart - reduces CO
- Reduce renin secretion and plasma levels of angiotensin II
- Reduce mortality after MI / chronic heart failure
- Bronchospasm / Cardiac Depression / Fatigue

Front 83

At what stage do α1 and AT1 receptor blockers disrupt smooth muscle contraction?

Back 83

(SMC bind --> G-Protein Activation)

Front 84

Mechanism of ACE inhibitors?

Back 84

- Block production of angiotensin II & inhibit bradykinin breakdown
- Best in Patients with high circulating renin

Front 85

For which demographic are they first line drugs?

Back 85

- White patients < 55 y/o
- African origin & older patients tend to have lower renin

Front 86

How does Angiotensin II compensate for arterial stenosis?

Back 86

Constricts efferent > afferent restoring glomerular capillary pressure

Front 87

Mechanism of Angiotensin Receptor Blockers (ARBs)

Back 87

- Block angiotensin II receptors
- 1st Lines drugs <55 years of age

Front 88

Amlodipine / verapamil / Diltiazem are all?

Back 88

- Calcium channel antagonists

Front 89

What is the mechanism of Calcium Channel Antagonists?

Back 89

- Block all VG Ca2+ channels
- Decrease TPR
- Tachycardia / Peripheral Oedema

Front 90

How can Ca2+ channel act as a voltage modulated dihydropyridine receptor?

Back 90

- Large polarisation to open state
- Dihydropyridine can bind to Inactive state and repolarise myocytes

Front 91

Mechanism of α1 adrenergic blockers?

Back 91

Block sympathetically mediated constriction of arterioles & decrease in TPR

Front 92

Mechanism of K Channel Agonsists?

Back 92

- Opens in smooth muscle cells resulting in hyperpol
- Reverse vasoconstrictor mediated depolarisation and contraction
- Severe vasodilator side effects so combined with diuretics and beta blockers

Front 93

NICE prescribing guidelines >55 / Black patients any age?

Back 93

- CCB / Diuretic
- If not effective (+ ACEI/ARB)
- If not effective CCB + Diuretic + ACEI/AII antagonist
- If still ineffective (+ spironolactone / B1 / A1 antagonist)

Front 94

NICE prescribing guidelines <55?

Back 94

- ACEI / ARB
- If ineffective (+CCB / Diuretic)
- If ineffective use all three
- If still ineffective (+ spironolactone / B1 / A1 antagonist)

Front 95

What is Phaeochromocytoma?

Back 95

Adrenal catecholamine (Adrenaline / Noradrenaline) secreting tumour

Front 96

What is Conn's Syndrome?

Back 96

Excess aldosterone synthesis

Front 97

What is Cushing's Syndrome?

Back 97

Excess cortisol synthesis