Case 4 Flashcards
1
Q
What are the roles of the cardiovascular system?
A
- Blood flow to tissues and organs (supply and demand)
- Homeostasis
Transport of hormones and signalling molecules
2
Q
Is there a direct connection between the two sides of the heart?
A
There is no direct connection with in adults (usually)
3
Q
Where does the heart pump blood to?
A
- Left side pumps into the aorta (systemic)
- Right side pumps to the pulmonary artery
4
Q
Which side of the heart is more prone to problems?
A
The left side (especially due to pressure)
5
Q
How does uidrectional blood flow in the heart occur?
A
- The valves prevent the back flow of blood
6
Q
Why does pressure drop in the circulation?
A
- Difference in pressure between aorta (highest) and vena cava (lowest)
- Energy is lost from the blood to the vessel wall resistance
- Blood flow through each circulation is proportional to pressure gradient
7
Q
What happens if you increase resistance to blood flow?
A
Make sit more difficult for the heart to pump blood to the peripheries
8
Q
What determines resistance (R) to blood flow?
A
The radius (r) of the arterioles
9
Q
What is stroke volume?
A
- Volume of blood pumped by one ventricle
- ~75mls
10
Q
What is cardiac output (CO)?
A
- Volume pumped per ventricle per minute
- 5L/min
11
Q
What is venous return (VR)?
A
- Volume of blood returning to the heart
- VR should equal CO
12
Q
What are intercalated disc?
A
- Junction between adjacent cells
- Packed filled with proteins that form gap junctions (allows electricity to move quickly)
13
Q
What is the SAN?
A
- a small group of cells
- one of few cells in the body that can spontaneously produce electricity- intrinsic property
14
Q
How is electrical energy spread in the heart?
A
- spontaneous depolarisation of the san (don’t see on ecg)
- comes out of san and spreads through the atria
- atria contracts (atria systole)
- av node depolarises and passes electricity down the ventricles - av node delay - allows atria muscle to contract to push more blood into the ventricles
- av node passes depolarisation down the interventricular septum
- then ventricular depolarisation occurs and then a wave of contraction follows it pushing the blood up and out of the heart
15
Q
What is the role of the annulus fibrosis?
A
- Non-conducting layer between atria and ventricles
- Electrically insulated the chambers from each other
16
Q
What is the P wave?
A
Atrial depolarisation
17
Q
What is the PR(Q) interval?
A
Interval between beginning of excitability of atria and ventricles (~0.16s)
18
Q
What is the QRS complex?
A
Ventricular depolarisation
Atrial repolarisation occurs but is obscured
19
Q
What is the Q-T interval?
A
Contraction occurring (~0.35s) but also includes ventricular repolarisation
20
Q
What is the S-T segment?
A
All ventricular tissue depolarised, contraction occurring
21
Q
What is the T wave?
A
Ventricular repolarisation
22
Q
How to calculate cardiac output?
A
HR X SV
23
Q
What helps venous return?
A
- Skeletal muscle pump/ contractions
- Respiratory pump
24
Q
What are the neurotransmitters that affect the SAN?
A
- sympathetic system - noradrenaline/ adrenaline
- parasympathetic- acetylcholine/ muscarinic receptors
25
How do sympathetic nerves affect heart rate?
- activation causes release of noradrenaline - binds to B1 adrenoceotors on the cardiac pacemaker and myocyte cell membrane
- increases opening of HCN channels in pacemaker cells - increase Na+ influx
- opens Ca2+ channels
- increase in slip of prepotential (phase 4)
- heart rate increases
26
What are HCN channels?
Channels that control the release of sodium into the cell and when activated allows depolarisation to occur quicker
27
How do parasympathetic nerves affect the heart rate?
- activation causes release of acetylcholine - binds to muscarinic cholinergic receptors
- decrease opening of HCN channels - decrease Na+ influx
- slows opening of Ca2+ channels
- opens additional K+ channels (ligand gated)
- hyperpolarises membrane and reduces slope of prepotential
- heart rate decreases
- the parasympathetic nerves constantly affect the SAN and is a very quick response
28
What are the sequence of mechanical events in the cardiac cycle?
1. Ventricular filling
2. Atrial contraction
3. Isovolumetric ventricular contraction
4. Ventricular ejection
5. Isovolumetric ventricular relaxation
29
What controls stroke volume?
- contractility
- preload (degree of stretch)
30
What is contractility?
Symapthetic nerves and calcium can change contractility (effected by mechanisms extrinsic to the heart)
It is changes in SV w/out changes in resting ventricular muscle fibre length
31
What is preload?
- Degree is stretch in the ventricles due to end diastolic pressure - dependent on end diastolic volume
- Changes in stroke volume dependant on resting ventricular muscle fibre length
- Mechanism intrinsic to the heart
32
What is cardiac workload?
Mechanisms regulating force of contraction and workload may be: heterometric (intrinsic) or homeometric (extrinsic)
33
What is starlings law of the heart?
Force of contraction is proportional to the initial fibre length in diastole
Almost empty chamber (low preload) -actin and myosin overlap is not optimal/ reduces ability to contract
Full ventricle (high preload) - some stretching of ventricular muscles/ optimum cross bridges available/ increased affinity of troponin C to Ca2+/ maximal force produced
Over full heart (heart failure) - actin and myosin are physically separated therefor preventing interaction so a reduced force is generated
34
What is the level of stretch of the heart determined by?
Venous return and the filling of the ventricle
35
Effects of sympathetic nerve stimulation on the heart:
- increased in stroke volume without a change in initial fibre length
- increased contractility - positive inotropic effect
Anything that is a beta1 agonist will increase contractility
36
What controls Mean Arterial Pressure (MAP)?
1. Blood volume
2. Effectiveness of the heart as a pump (CO)!! - determined by heart rate and stroke volume
3. Resistance of the system to blood flow!! - determined by diameter of arterioles
4. Relative distribution of blood between arterial and venous blood vessels
37
How do you calculate MAP?
MAP = CO X TPR (total peripheral resistance)
38
What do baroreceptors do?
Detect changes in blood pressure and makes sure they’re kept within the appropriate range
39
When would you offer ambulatory blood pressure monitoring (ABPM)?
Offer it if the clinical BP is between 140:90 mmHg and 180/120mmHg to confirm the diagnosis of hypertension
40
What is the blood pressure measurement that confirms hypertension?
- Clinic blood pressure of 140/90 mmHg or higher (150/90 mmHg for adults ages 80 and over)
- ABPM daytime average or HBPM average of 135/85 mmHg or higher (145/85 mmHg for adults aged 80 and over)
41
What is stage 1 hypertension?
Clinic blood pressure ranging from 140/90 mmHg to 159/99 mmHg and subsequent ABPM daytime average or HBPM average BP ranging from 135/85 mmHg to 149/94 mmHg
42
What is stage 2 hypertension?
Clinic BP of 160/100 mmHg or higher but less than 180/120 mmHg and subsequent ABPM daytime average or HBPM average BP of 150/95 mmHg or higher
43
Which type of hypertension usually has no identifiable cause and develops gradually over years?
Essential hypertension
44
What are some recognised links (causes) to secondary hypertension?
1. Diabetes
2. Kidney disease
3. Thyroid disease
4. Sleep apnoea (secondary cause)
45
Which type of hypertension doesn’t have a genetic link?
Secondary hypertension
46
What mechanisms should prevent elevations in arterial BP?
Baroreceptors should detect the change and increase nerve activity to activate the parasympathetic system to decrease the blood pressure
Nerve activity however reduces with sustained high blood pressure
47
What is atherosclerosis?
The build up of fatty plaques in the arteries
48
What is the mechanism of action of calcium channel blockers?
- They inhibit the influx of calcium ions
- They act on: myocardial muscles (inhibit contractility); myocardial conducting system (inhibit formation and propagation of depolarisation); vascular smooth muscle (coronary or systematic vascular tone reduced/ vascodilation)
49
What is the pharmacokinetics of calcium channel blockers?
- oral route: bioavailability 60%
- Half-life of amlodopine 30-50hrs
- Steady-state plasma concentrations - 7-8 days of daily dosing
- Liver CYP450 - slowly metabolised
- Renal elimination but poor renal function does not significantly reduce elimination
50
What is the mechanism of action if ACE inhibitors?
Inhibits the angiotensin-converting enzyme in the renin-angiotensin system
51
What is the pharmacokinetics of lisinopril?
- Oral administration: 25% bioavailability
- Peak plasma conc: 4-8h - half life 12h
- Water soluble - not metabolised in the liver and undergoes renal excretion unchanged
52
What is the first line treatment of hypertension for those over 55?
Calcium channel blockers - for those of Afro Caribbean decent too
53
What is the first line treatment of hypertension for those under 55?
ACE inhibitors
54
What is the mechanism of action of ARBs?
Selective competitive blockers of angiotensin II at the AT1 receptor
55
What are the advantages of ARBs?
No dry cough
56
What is the pharmacokinetics of losartan?
- Oral administration: 32% bioavailability
- First-pass metabolism 14% to active metabolite which is more potent, non-competitive and longer acting
- Cytochrome P450 metabolism - half-life of 2h and 3-9h for metabolite
- Extensive plasma protein binding
- Excreted in urine and bile
57
What is the mechanism of action of thiazide-like diuretics (e.g. indapamide)?
- Inhibition of Na+ and Cl- réabsorption from the DCT by blocking the Na+-Cl- symporter
- At lower doses vasodilation is more prominent than diuresis
58
What is the pharmacokinetics of thiazide-like diuretics?
- Oral administration
- 75% plasma protein bound
59
What are B-blockers competitive inhibitors of?
Catecholamines
60
What are the two types of adrenoreceptors?
- Alpha: 1- IP3/DG (increase); 2-cAMP (decrease)
- Beta: 1- cAMP; 2- cAMP; 3- cAMP (all increase)
61
What is epichlorohydrin?
A special epoxide for providing a 1,2,3-substituted compound
62
What were the side effects caused by first generation beta blockers (pindolol/timolol)?
- Crossed the BBB - dizziness/ sedation
- Bronchoconstriction in asthmatics
- Lower cardiac output
63
What was the issue with propranolol?
- Has a high logP = 3.66 therefore highly lipophilic
- Possible CNS side effects due to BBB penetration
64
How was propranolol altered/ modified?
- Reduce logP, take out one aromatic ring, use a logP lowering group like acetamide and sulphonamide
65
How were 2nd gen beta blockers made to be less lipophilic (eg practolol)?
- made less potent than propranolol
- more selective so fewer CNS side effects (more polar, logP 0.79)
- B1 selective over B2 (cardio selective over vascular and bronchial)
- contain extended para subsitute
66
What are the symptoms of high BP?
- **Asymptomatic**
- Headaches
- Eye issues (very red eyes); problems with the retina and blood vessels burst
- primary - no know cause
- secondary - know cause
- tumour on adrenal glands can elevate Bp
- Meds (NSAIDS)
67
What to do when diagnosing hypertension?
- measure both arms
- irregular pulse - has to be measure manually
- 140/90mmHg or higher then take another measurement and still high then take another
- record the lower of the last two measurements as the clinic BP
68
What is stage 1 hypertension?
Clinical blood pressure is greater than 140/90 mmHg and subsequent ambulatory BP monitoring average or home BP monitoring is greater than 135/85mmHg
69
What is stage 2 hypertension?
Clinic BP is greater than 160/100 mmHg and subsequent ABPM average is greater than 150/95 mmHg
70
What is stage 3 hypertension?
Clinic systole BP is greater than 180 mmHg or diastolic BP is greater than 110 mmHg
71
What sort of lifestyle advice would you give to those with hypertension?
- lose weight is over weight
- exercise
- fresh fruit and veg
- reduce salt and smoking and alcohol
72
What is the first line treatment for hypertension?
- <55 - ACE inhibitors or A2RBs
- >55 or black people of African/ Caribbean family origin of any age - calcium channel blocker
- if CCB is unsuitable/ not tolerated offer a thiazide-like diuretic
73
How do ACE inhibitors work and what to consider when prescribing?
- target the conversions of angiotensin 1 to angiotensin 2 (a vasoconstrictor) so therefore it prevents the creation of a vasoconstrictor - can make you dizzy (postural hypotension- systolic drops by 20 and diastolic drops by 10) as they allow vasodilation
- start low and go slow
- check U&Es - can affect kidney function (can cause hyperkalamia)
- care with ADRs (a dry cough)
- drug interactions (especially those that cause hyperkalamia)
- angioedema - allergic to ACE inhibitors and more likely to occur in certain ethnic groups
74
How to A2RBs work and points to consider when prescribing?
- stop the activity of angiotensin 2 (do not stop the conversion)
- don’t cause a cough
- more expensive than ACE inhibitors
75
How do dihydropyridine CCBs work and points to consider when prescribing?
- Caution in heart failure
- ADRs - oedema (particularly in the legs), (don’t want to give to those with heart failure)
- Drug interactions - beta-blockers (can cause bad bradycardia)
- Food interactions- may also interact with grapefruit juice (CYP450 inhibitors)
76
What are the three types of CCBs?
1. Benzodiazepines
2. Diphenhydramine
3. Dihydropyridines (interested in these for hypertension)
77
How do thiazide-like diuretics work and points to consider when prescribing?
- Indapamide and chlortalidone now replace bendroflimethiazide
- Give the dose early in the morning
- Higher dose cause more side effects with little effect on BP
- Cab disturb electrolytes (which can be clinically significant) - can increase glucose and uric acid (cause gout?)
- Loop diuretics (e.g. furosemide) are NOT used to treat hypertension
78
What is the second line treatment for hypertension?
- CCB in combination with either an ACE inhibitor or an ARB
- If a CCB is not suitable or tolerate offer a thiazide-like diuretic
- For black people of African or Caribbean descent, consider an ARB in preference to an ACE inhibitor, in combination with a CCB
79
What is the third line treatment for hypertension?
- Before progressing to step 3, ensure that treatment doses at step 2 are optimal
- We should then look at the combination of ACE inhibition (or A2RB), CCB and thiazide-like diuretic
80
What is the fourth line treatment for hypertension?
- If BP remains a over 140/90 mmHg after ACE inhibitor (or A2RB), a CCB and a diuretic, it is known as resistant hypertension
- Treatment options include: additional diuretics (potassium sparing diuretic (spirolactone)) ; using higher dose thiazide-like diuretic; using alpha or beta-blocker
81
How do alpha blockers treat hypertension and things to consider when prescribing?
- Includes: Doxazosin, Prazosin, Terazosin
- Also used to treat benign prostatic hypertrophy
- Side effects: postural hypotension; urinary incontinence
82
How do beta blockers work and things to consider when prescribing?
- Less common nowadays - end in olol
- Target beta receptors in the heart (beta1) - makes patients tired
- Selectivity re B1 + B2 receptors and bronchspasm?
- ADRs: coldness of the extremities; sleep disturbances; caution when stopping (rebound tachycardia - Sympathetic nervous system may increase)
83
What is ACS?
- Acute coronary syndrome
- An umbrella term that encompasses three things: unstable angina; myocardial infarction (STEMI- ST segment elevation myocardial infarction and NSTEMI- Non-ST segment elevation myocardial infarction)
84
What is MI?
- Myocardial ischaemia - reduced blood flow to the cardiac tissue- less O2 to perfusé the cardiac cells
- Myocardial infarction- death of cardiac cells
85
What are causes of ACS?
- Due to sub total (UA+NSTEMI) or total (STEMI) coronary artery occlusion
- Occurs as a complication of advanced atherosclerosis/ atherosclerosis CAD
- Triggered by an athermatous plaque disruption (rupture or erosion) -> coronary thrombosis-> formation of thrombi (either total occlusion or sub-total occlusion)
86
What is unstable angina (UA) characterised by?
- Typically diagnosed with SA first
- Acceleration in frequesn or severity of chest pain
- New onset angina pain
- Angina chest pain that abruptly occurs at rest
- No enzymatic evidence (biochemistry) of myocardial necrosis
- Presence of an active pro-thrombotic surface at the site of plaque rupture —> increased risk of MI
87
What is NSTEMI characterised by?
- Unstable plaque rupture + thrombosis-> partial occlusion of artery
- Postive enzymatic evidence (biochemistry) of myocardial necrosis
- Presence of persistent pro-thrombotic surface at site of plaque rupture—> increased roak of recurrent ischaemic episodes
88
What is STEMI characteristed by?
- Unstable plaque rupture + thrombosis—> complete occlusion of artery
- Positive enzymatic evidence (biochemistry) of myocardial necrosis
- Ishaemia-induced electro instability —> increased risk of sudden cardiac death
89
What is the difference in ECG of STEMI and NSTEMI?
- STEMI - ST elevations
- NSTEMI - ST depressions
-UA - no change
90
What is acute myocardial infarction?
- Death of heart muscle
- Ultimate result of sustained myocardial ischaemia
- High mortality rate
- Necrosis of myocardial tissue within 20-40 minutes of occlusion
- Significant necrosis at 2-3 hrs
91
Major clinical features of MI
- Pain - be specific - sharp heavy pain in the chest that starts centrally and radiates to the left hand side (may include the shoulder blade)
- Lasting >20 minutes
- Often associated with nausea, sweating, dyspnoea, palpitations
- May present without chest pain (CP) = ‘silent infarct’ (e.g. in elderly/ DM)
- Can also experience: hypotension, dizziness, syncope (fainting)
- ECG changes: T wave inversion; ST segment elevation; Q wave development
- Enzymatic changes (biochemistry): troponin enzymes released by heart tissue
92
What are the ECG changes in MI?
- T wave inversion
- ST segment elevation
- Q wave development
93
What are the enzymatic changes (biochemistry) of an MI?
- cardiac troponin (T and I) levels are the most established and specific markers of myocardial necrosis
- serum levels increase within 3-12h from the onset of chest pain, peak at 24-48h and reduce to baseline over 5-14 days
- Troponin T: can be relaxed from cardiac muscle or skeletal muscle (less specific)
- Troponin I: extremely specific for cardiac muscle = ideal marker for cardiac injury
- Emerging bio markers; heart fatty acid-binding protein; B-type natriuretic peptide —> newest focus; ischaemia-modified albumin; co-peptin
94
Diagnosing criteria for MI
- rise and/or fall of serum cardiac biomarkers
- plus at least one of the following: symptoms of ischaemia; ECG changes (new ST/T wave changes); development of Q waves; loss of myocardium on imaging
95
Risk factors of MI
- Non-modifiable: age; male gender; family history of IHD; certain ethnic groups
- Modifiable: smoking; hypertension; DM; hyperlipidaemia; obesity; sedentary lifestyle
96
Clinical management principles of MI
- Relieve pain
- Recognise (working diagnosis to definite diagnosis)
- Treat
- Prevent complications
- *Myocardial salvage* (pharmacological and/ or non-pharmacological): reduce myocardial oxygen demand (B2 cardio selective B-blockers and nitrates); restore myocardial blood supply through reperfusion (either thrombolytic ‘clot busters’; anticoagulant + antiplatelet combination; PCA/stent)
- *Improve survival* (pharmacological and/ or non-pharmacological): secondary prevention
97
How do you improve survival of an MI?
- termed secondary prevention
- combination of pharmacological and non pharmacological
- will be overlap between salvaging and improving survival - often life long meds post MI
- SAAB+GTN: statin (atorvastatin-gold standard); ACEi; dual antiplatelet (2 for 12 months then move to one); beta blocker; GTN
- Non pharmacological- **cardiac rehabilitation**
98
What is ischaemic heart disease?
- Deprivation of supply to cardiac tissue causing cell death (irreversible)
- Angina symptoms
- Heart attack
99
What is cardiac failure?
- Inability of heart to distribute blood
- Heart failure
100
What is cardiac dysrhythimia?
- Disruption of contraction control
- Cardiac arrest
101
How does adaptation to O2 demand change in the heart?
- Mainly by changes of n vascular resistance
- O2 demand = blood flow X arteriovenous O2 concentration difference
- O2 demand increases (hypertension….
INCOMPLETE
102
What are metabolic autoregulatory factors of the heart?
103
What are endothelium-mediated auto regulatory factors relating to the heart?
- Bradykinin, histamine and Ach are vasodilators
- Act indirectly by releasing nitric oxide (NO), which diffuses into vascular muscle
- Raises cGMP, activates protein kinase G - causing vascular relaxation
104
What are neurohumoral autoregulatory factors relating to the heart?
105
Causes of ischaemic heart disease (coronary heart disease)
- Atherosclerosis (most cases)
- Arteritis
- Embolism and endocarditis
- Coronary artery wall thickening: amylodosis
- Coronary spasm (eg cocaine induced spasm)
- Congenital artery disease: arteriovenous fistula
106
Modifiable fish factors for ischaemic heart disease
- Hypertension
- Hypercholestérolémia
- Smoking
- Diabetes mellitus
- Sedentary life style
- Obesity
107
Non modifiable risk factors of Ischaemic heart disease
- Age
- Male gender
- Family history
108
What is angina?
-Chest pains - not a disease itself
-Primary symptom associated with ischaemic heart disease
-Caused by transient episodes of myocardial cardiac ischaemia
-Pain from myocardium after switching to anaerobic metabolism (low O2 supply)
109
What are the three types of angina pectoris?
1. Stable
2. Unstable
3. Varient
110
What is stable angina?
111
What is unstable angina?
112
What is varient angina?
- Focal/ diffuse coronary vasospasm
- Pain resulting from lack of O2 …
113
Consequences of myocardial ATP deficiency
1. Impairment of ventricular systolic pumping action
2. Decreased compliance of myocardium during diastole
3. Pulmonary congestion and dyspnea
114
Learn the nitrates oathway
115
Give two examples of nitrates
GTN and isosoribide mononitrate
116
Wat are the two actions of nicotandil?
1.
2.
117
What is the mechanism of beta blockers?
118
What are causes of atherosclerosis?
Hyperlipidemia
Smoking
Primary inherited disorders
Secondary lipid disorders
119
What are the consequences of atherosclerosis?
- Narrowing of the lumen leading to IHD
- Stiffening of the vessel wall (calcification)
- Thrombus obstructing residual lumen and causing peripheral embolism (eg cerebral infarction, stroke)
…
120
Prophylactic intervention got atherosclerosis
- Dietary changes to reduce cholesterol and lipids
- Cessation of smoking
- Control of BP
- Control of diabetes
- Regular, moderate exercise
- Drugs to reduce plasma cholesterol
121
Pharmacological interventions for lowering lipid levels
122
What is the mechanism of action for statins?
123
What are the side effects of statins?
124
What drug is used to prevent cholesterol absorption?
Resins eg …
125
What are side effects of resins?
126
What is a mechanism of action of resins?
127
Which drug is used to reduce VLDL secretion?
Niacin (nicotine acide/ vitamin B3)
128
Which drug is used to increase the synthesis of lipoprotein lipase?
Fibrates (eg gemfibrozol, fenofibrate)
129
What are radioisotopes?
Radioactive isotopes that are produced as a result of natural decay
130
What is diagnostic imaging?
Exploiting the tissue penetration of gamma rays derived from nuclear decay or positron annihilation
131
What is targeted therapy?
Exploiting the cellular toxicity of non-penetrating alpha and beta particles and secondary electrons
132
What is a cyclotron?
- A particle accelerator
- An electrically powered machine producing a beam of charged particles
133
What is PET?
Positron emission tomography
134
What is PET?
Positron emission tomography
135
What is SPECT?
Single photon emission computed tomography
