Cardio Flashcards
1
Q
Why are arterioles, and to a lesser extent, arteries called resistance vessels?
A
They act as muscular sphincters to provide vascular resistance and redirect flow as required. This is the main regulator of blood pressure
2
Q
What is a name for capillaries, venous sinusoids and small vessels?
A
Exchange vessels
3
Q
What is the distribution of blood normally?
A
65% in peripheral veins
20% in heart and lungs
10% in peripheral arteries
5% capillaries
4
Q
What can change blood distribution?
A
Exercise, where blood is diverted to skeletal muscle and heart
5
Q
What is the tunica intima?
A
The innermost layer of vessels.
Endothelium which lines the entire vascular system
6
Q
What is the tunica media?
A
Middle layer of vessels (absent in capillaries)
Thickest layer in arteries
Comprised of muscle tissue, elastic fibres and collagen
7
Q
What is the tunica adventitia?
A
Outermost layer
Comprised of connective tissues, nerves, vessel capillaries
8
Q
What are the three types of capillaries?
A
Continuous - continuous cytoplasm, continuous basal lamina, bidirectional transport via transcytosis - in the brain, thyroid, bone and lung
Fenestrated - discontinuous cytoplasm, fenestrations may have a diaphragm, unidirectional filtration, continuous basal lamina. - villi, kidneys
Discontinuous - discontinuous cytoplasm, bidirectional filtration, discontinuous basal lamina. - spleen
9
Q
What are the layers of the heart
A
Endocardium - innermost
Myocardium - heart muscle
Visceral later - inner serous layer
Pericardial cavity
Parietal layer - outer serous layer
Fibrous layer
10
Q
What are the borders of the heart?
A
Upper left 2nd intercostal space Lower right 2nd intercostal space 6th right costal cartilage 5th left intercostal space T4/5 - T8/9
11
Q
What is diastole
A
When the ventricles are relaxed. At the end of diastole, both atria contract. The volume of blood in the ventricles after this is the end diastolic volume
12
Q
What is systole
A
When ventricles contact. Blood is also entering atria
13
Q
What is isovolumetric contraction? And what happens after?
A
Between the closing of the AV valves and the opening of the aortic and pulmonic valves. Ventricular pressure increases as contraction doesn’t push out any blood
Then comes rapid ejection phase
As ventricular depolarisation occurs (t wave), pressure in ventricles reduce and force of ejection drops. This is reduced ejection phase as blood is pulled out by the movement of blood
14
Q
What is stroke volume
A
Amount of blood pumped out of each ventricle per beat. Around 75ml but may double in exercise
15
Q
What is cardiac output?
A
Stroke volume x heart rate
Around 5L at rest but up to 25L during exercise
16
Q
What can affect cardiac output?
A
Preload - the stretch on the heart muscle due to the end diastolic volume - this increases sarcomere length and therefore an increase in contractile force, increasing stroke volume
Afterload - the load that the ventricles must pump blood against. If peripheral vascular resistance increases, cardiac output will decrease initially but then return to normal as Frank starling law takes place. Increased end diastolic volume due to increased resistance –> greater stretch of sarcomeres –> greater stroke volume increased
Functionality of the heart - encompasses heart rate and contractility which is modulated by the SNS and PSNS
17
Q
Why is cardiac muscle termed myogenic?
A
Because cells in the sinoatrial node generate their own regular, spontaneous action potentials
18
Q
Which ions cause the depolarisation in heart cells?
A
Calcium
19
Q
What are the three phases in the sinoatrial nodal action potentials?
A
At the end of depolarisation, the membrane potential is around -60mv. Ion channels open which allow a slow inward flow of Na called funny currents. This depolarises the cell, and at around -50mv, T-type calcium channels open, causing phase 4
Phase 4 - spontaneous depolarisation that occurs during diastole and triggers the action potential once the membrane potential reaches threshold ~ -40mv
At -40mv L-type calcium channels open
Phase 0 - T-type calcium channels and funny current channels close.
Phase 3 - K channels open and flows outwards, depolarising the cell and L-type calcium channels close. Keep flowing out until the cell is at around -60mv again and the cycle is spontaneously repeated
20
Q
Explain the action potentials in non-pacemaker cells in the heart
A
Have a true resting membrane potential - phase 4
When rapidly depolarised to threshold of around -70mv there is rapid depolarisation (phase 0) causes by sodium channels
Phase 1 is the initial repolarisation by opening of transient K channels
This repolarisation is delayed by the large inward slow Ca at the same time which is long lasting. This causes a plateau which distinguishes cardiac action potentials from skeletal muscle or nerves
Phase 3 is when calcium channels close and repolarisation happens quickly again
21
Q
What are cardiomyocytes joined together with?
A
Intercalated discs made of:
- fascia adherens which are anchoring sites for actin and allow for transmission of force
- desmosomes which stop separation of myocytes via intermediate filaments
- gap junctions which allow for the passage of action potentials cell to cell via connexons
22
Q
What is excitation-contraction coupling?
A
The process where an action potential triggers a myocyte to contract
When the myocyte is depolarised by an action potential, calcium ions enter (phase 2) through L-type channels located on the sarcolemma. This calcium triggers calcium to be released form the sarcoplasmic reticulum through ryanodine receptors. This is called calcium induced calcium release.
This free calcium binds to troponin C. This induced a conformational change which exposes a site on actin that is able to bind to the myosin ATPase on the myosin head. This results in ATP hydrolysis that supplies energy for a conformational change in the actin-myosin complex.
They slide past each other and contract the sarcomere.
At the end of phase 2, calcium concentration decreases leading to troponin 1 once again inhibiting the actin binding site and ATP binds to myosin head. The sarcomere returns to initial length
23
Q
What is the order in which parts of the heart contract?
A
SAN –> atria –> AVN –> annulus fibrosis –> ventricles (bundle of His and Purkinje fibres)
24
Q
What is the annulus fibrosis?
A
Non conducting band between atria and ventricles
25
How long is a large square on the ECG?
0.2 seconds and 0.5mV
26
What are the parts of the ECG
P - depolarisation of the atria
Q- left to right depolarisation of the interventricular septum
R- depolarisation of main mass of ventricles
S- depolarisation of last part of ventricles at base
T - repolarisation of ventricles
27
Why isn't the repolarisation of the atria and other things seen on the ECG?
Too diffuse
28
Why is the T wave positive?
Although it is repolarisation, the wave progresses from the base towards the apex. The change in polarity and direction cancel each other out. In pathological conditions where the action potential is prolonged, or the conduction from apex to base is slow, the T wave may be inverted
29
Which vessels provide the most resistance?
Arterioles as they have the thickest walls in relation to their lumen
30
What is the role of capillary hydrostatic pressure?
To drive fluid out of the capillary into the interstitium
| Pressure drops between the arteriole end and the venule end, meaning fluid is reabsorbed at the venule end.
31
What is the role of capillary oncotic pressure
Generates by proteins such as albumin
| Fluid to protein ratio decreases towards the venule end which pulls fluid back into the capillary
32
What is oedema caused by?
```
Increased interstitial oncotic pressure
Increased venule hydrostatic pressure
Increased arteriolar hydrostatic pressure
Decreased plasma oncotic pressure
Lymphatic blockage
```
33
What are the body fluid volumes?
Intracellular - 25L
Extracellular - 15L total
- interstitial fluid -12L
- plasma - 3L
34
How is blood pressure calculated
Cardiac output x peripheral vascular resistance
35
How are vessels modulated?
Smooth muscle in the medial layer innervated by postganglionic sympathetic neurones
Noradrenaline acts at alpha 1 adrenoreceptors and causes vasoconstriction
Adrenaline acts at beta 2 adrenoreceptors and causes vasodilation
Angiotensin II and vasopressin cause vasoconstriction
Nitric oxide causes vasodilation
Endothelin causes vasoconstriction
36
Which cells are involved with the RAAS
Cells in the macula densa in the renal tubules are sensitive to sodium concentration
37
What happens if the cells in the macula densa sense low sodium concentrations
Send a signal to juxtaglomerular cells in the kidney glomerulus to release renin, which cleaves angiotensinogen into angiotensin I. This is in turn converted to angiotensin II by angiotensin converting enzyme (ACE) - synthesised in the lung
Angiotensin II has the following effects:
- arteriolar constrictor - preserves blood pressure
- aldosterone release - retention of sodium and water in kidney
- vasopressin secretion - retention of water
- Thirst
38
What's the opposite of the RAAS system?
ANP and BNP
Cause excretion of water and sodium and powerful vasodilators when higher blood volume is sensed
39
What are the major afferent sensors other then the juxtaglomerular apparatus?
Baroreceptors in the arch of the aorta (vagus nerve) and corotid sinus (glossopharyngeal nerve)
40
What causes the release of endothelin I and reduction of Nitric oxide synthesis
Endothelial damage
41
Describe nitric oxide
Anti aggregatory vasodilator
Formed from L-arginine by NO synthase in response to stress, blood flow, acetylcholine and bradykinin. It converts GTP into cGMP in target cells causing relaxation.
L-monomethyl arginine is an inhibitor of NO synthase
42
Describe endothelin 1
Released by the endothelium in response to many vasoconstrictors.
It is a a potent vasoconstrictor which stimulates two types of receptor, ETa and ETb
ETa - vasoconstriction, hypertension, endothelial dysfunction, arterial stiffness, atherosclerosis, inflammation, fibrosis, insulin resistance
ETb - natriuresis, vasodilation, ETa clearance
43
How does the body respond to haemorrhage
Decreased:
```
Intravascular volume
Ventricular filling
Blood pressure
Capillary hydrostatic pressure
Venous return
Cardiac output
Renal perfusion
```
Afferent receptors are activated:
Carotid baroreceptors and aortic arch baroreceptors sense decrease in pressure
Atrial volume stretch receptors and juxtaglomerular sensors sense decrease in volume
Efferent signals are activated:
Tachycardia and increased contractility stimulated by Beta 1 adrenoreceptors to increase cardiac output and blood pressure
Alpha 1 adrenoreceptors cause vasoconstriction to increase peripheral resistance and sacrifice blood flow to less vital systems e.g. GI and skin - become cold and pale
Venoconstriction by A1 reduce reservoir function, reduce venous return to the heart and increase cardiac output via Frank starling mechanism
Catecholamine release
Renin release to reduce loss of water and salt in kidney
44
What symptoms does hypovolemic shock produce
Sweating
Low urine output
Confusion due to reduced cerebral perfusion
45
Describe the process of atheroma
Tunica intima is damaged by chemicals in the blood, components of cigarette smoke, hypertension or infections
Injured cells release chemotactic agents and begin to transport band modify lipids, particularly LDLs. The built up LDLs are oxidised in the inflammatory environment, damaging nearby cells. This also attracts macrophages. Some of these macrophages become engorged with LDL and become foam cells. Built up foam cells form a fatty streak.
Smooth muscle cells from the media migrate and deposit elastic and collagen fibres, thickening the intima and producing lesions with a core of dead and dying foam cells called atherosclerotic plaques. Initially, vessel walls will expand to accommodate the growing plaque but, eventually, it will start to block parts of the lumen. This is classed as atherosclerosis.
Cells in the centre continue to die and calcium is deposited. Collagen production decreases and the plaque may rupture. - complicated plaque
46
What is the main function of a lipoprotein
Transportation of triacylglycerol and cholesterol
47
Describe a lipoprotein
Triacylglycerol (TAG), cholesterol and cholesteryl esters surrounded by a phospholipid monolayer
Have apolipoproteins which have a key role in movement of the lipoprotein
48
Describe chylomicrons
```
Biggest
Lowest density
Dietary source
TAG rich
Hydrolysed in adipose and muscle tissue
ApoB receptors
```
Dietary lipids, bile and cholesterol form chylomicrons in the gut
Transport TAG into the body
Release free fatty acids (FFAs) and form chylomicron remnants which are either recycled in the liver or absorbed by macrophages
49
Describe VLDL
```
Second biggest
Second least dense
Synthesised in liver
TAG rich
Transportation function
ApoB receptors
```
Progressively become more dense through release of FFAs due to lipoprotein lipase (LPL), forming IDLs and LDLs. This happens on cell membranes
The resultant LDL is recycled in the liver or absorbed by macrophages
50
Describe LDL
```
Second smallest
Second densest
Derived from VLDL, with the same function
Cholesterol rich
ApoB receptors
```
51
Describe HDL
```
Smallest
Densest
Synthesised from APO-A1 in the liver
Cholesterol rich
Function of removing cholesterol
"Good" cholesterol
ApoA-1 receptors
```
APO-A1 is converted to HDL3 at the ABC-A1 receptor in macrophages, catalysed by LCAT
HDL3 is then converted to HDL2 at the SR-B1 receptor on macrophages, catalysed by LCAT
HDL2 exchanges cholesterol esters for cholesterol with LDLs, reducing body cholesterol.
HDL2 is then recycled in the liver at scavenger receptors or recycled to HDL3
52
What is the treatment for hyperlipidemia?
Diet, weight, stop smoking, moderate alcohol
Statins - inhibit HMG-CoA reductase, preventing production of cholesterol
Ezetimibe - inhibits chylomicron absorption
Stanol esters - reduces chylomicron absorption (weak)
Nicotinic acid - increases HDL, decreases triglycerides
53
What is ehlers-danlos syndrome
Genetic connective tissue disorder, autosomal dominant, collagen related
54
What is Marfan syndrome
Genetic connective tissue disorder, autosomal dominant, fibrillin related
55
What is Virchow's triad
Endothelial injury
- ulcerated atheromatous plaque
- left ventricular endocardium after MI
- abnormal cardiac valves
Abnormal/stasis of blood flow
- disrupts laminar flow
- prevents dilution of clotting factors
- retards inflow of inhibitors to clotting factors
- promotes endothelial cell activation
Hypercoagulabilty
- alteration of copying cascade
- genetic predisposition
- acquired (e.g. after surgery)
56
What are mural thrombi?
Applied to one wall of underlying structure
Occur in capacious structures such as cardiac cavities and aorta
57
What are lines of zahn?
Alternating bands if fibrin/platelets (white) and erythrocytes (pink)
Occur in thrombi (especially formed near the heart or aorta)
Do not occur in clots formed after death. Can be used to tell if the clot was a cause of death
58
What is an embolism
A detached intravascular solid, liquid or gaseous mass that is carried by the blood to a site that is distant from its point of origin.
Almost always thromboembolism
Can also be:
Amniotic fluid
Gas such as nitrogen in divers or injected
Bone fragments
Large emboli may lodge at the bifurcation of the pulmonary artery and can cause sudden death as they obstruct the entire pulmonary circulation
59
What are the types of infarct
Red (haemorrhagic) - dual circulation e.g. lung or venous occlusion
White - anaemic - arterial occlusion with a single blood supply e.g. heart
Septic - infected infarcts
60
What are factors which influence development of an infarction
Dual or single blood supply
Rate of development - rapid due to embolism or gradual such as atheroma build up
Vulnerability of tissue - heart and kidney susceptible
Oxygen content of blood - hypoxia worsens
61
Describe the clotting cascade
Endothelial damage - platelet attracted to lower prostacyclin levels and exposed collagen. Thromboxane (TXA2) and serotonin are released causing vasoconstriction
Platelets bind to glycoprotein receptors aided by collagen bound von-willebrand factor in microfibrils
This causes confirmation change
Platelets bind to different glycoprotein receptors aided by vWF
Platelets adhere to more glycoprotein receptors aided by fibrinogen
TXA2 causes release of dense granules
Thrombin and tissue factors activate clotting cascade
Intrinsic pathway initiated by collagen exposure - eventually producing factor Xa
Extrinsic pathway initiated by TF and also produces Xa
Xa then converts prothrombin to thrombin which converts fibrinogen to fibrin
62
What is the fibrinolysis pathway
Plasminogen --> plasmin --> fibrin degradation products
63
What does prothrombin time measure?
Extrinsic + common pathway
64
What does the activated partial thromboplastin time measure?
Intrinsic + common pathways
65
What are examples of hypocoagulation
Haemophilia A - sex linked recessive, factor VIII dysfunction/deficiency
Haemophilia B - sex linked recessive, factor IX dysfunction/deficiency
Factor underproduction - commonly due to liver failure resulting in reduced vit K - factors dependent on vit K
are II, VII, IX and X
Von willebrand disease - autosomal dominant, vWF dysfunction/deficiency - carries fVIII - most common heritable bleeding disorder
Thrombocytopenia - decrease in platelets
Scurvy - no collagen strengthening due to lack of vit C
Ehlers-danlos syndrome - connective tissue disorder
Bone marrow failure
66
What are examples of hypercoagulabilty
Disseminated intravascular coagulation (DIC) - widespread overactivation of the clotting cascade
Thrombophilia - increased tendency to clot
67
What is sinus arrhythmia?
A normal phenomenon where the the sinus node fires at variable rates, depending on parasympathetic vagus nerve activity due to inhalation, exhalation.
SAN us programmed to fire at around 100BPM
This is slowed by the normal action of the parasympathetic nervous system which releases acetylcholine from the vagus nerve which decreases cAMP which reduces ion channel activity
68
Atrial flutter
Sinus rate of 250-350 beats/min
| Normal QRS complex in a 2/3-1 ratio with abnormal complexes. This has a characteristic saw tooth pattern on ECG
69
Atrial fibrillation
Uncoordinated atrial depolarisations
This is very common, particularly in the elderly
Typically at 400-600/min however the AVN can only transmit at 200/min
This leads to reduced filling, reduced cardiac output and can lead to thrombus formation. There are no p waves. Known as irregularly irregular
70
Ventricular flutter
Very rapid ventricular depolarisations >250/min
| Sine wave appearance, leads to fibrillation
71
Ventricular fibrillation
Uncoordinated ventricular depolarisations
Leads to death quickly if not converted to a rhythm compatible with life
Most common rhythm seen in cardiac arrest - no longer pumps blood properly - leads to shock, asystole and sudden cardiac death
There is a high recurrence rate
72
Supraventricular tachycardia
Usually caused by re-entry currents within the atria or between ventricles and atria producing heart rates of 140-250 beats/min
73
AV nodal block
Problems with coordination between atria and ventricles. Ventricles set their own pace. Can be caused by ischaemia
First degree - PR interval > 0.2 secs
Second degree - progressive prolongation of PR interval with dropped beats
Third degree - no association between P and QRS complex
74
Types of cardial infarcts
Sub-endocardial infarcts - many infarcts are located just outside the endocardial surface, rather than further away. This is because the branches of the coronary arteries supply the endocardial region last. Therefore it is the last to receive oxygen and the most vulnerable to ischaemia.
Transmural infarct - the whole wall us infarcted m results in pericarditis in response to pericardial necrosis
75
Describe infarct development in the heart.
<18h no pathological signs
1-2d pale muscle, oedema, neutrophil infiltration
3-7d yellow centre with haemorrhagic border, necrosis, inflammation, granulation tissue
1-3w pale and thin muscles glanulation tissue progressing to fibrosis
3-6w silvery scar becoming tough and white, dense fibrosis
76
What are the tests for MI
Troponin - found in sarcomeres and is highly specific for cardiac tissue
Others include creatine kinase and raised BNP (this is even more specific but is not currently funded by NHS)
77
What are the ECG changes in STEMI
Within hours - ST elevation
Days 1-2 - Q depression
Days later - t wave inversion
Weeks later - normal with persisting Q depression
78
What is STEMI
Most severe type of MI
Probable transmural necrosis due to complete occlusion
79
What is NSTEMI
No ECG changes
Caused by incomplete or temporary occlusion
Biomarkers are present
80
What are the types of heart failure
Acute - rapid onset, definable cause
Chronic - slow onset, ischaemic or valvular disease
Acute on chronic - chronic failure exacerbated by acute event
Can be right, left or both (congestive) heart failure
81
Describe LV failure
Dominates hypertensive and ischaemic heart failure
Causes pulmonary oedema because left ventricle is unable to pump blood into circulation therefore blood backs up and is forced into pulmonary tissue
This causes hypertension and eventually RV failure
82
Describe RV failure
Often secondary to LV failure
Related to intrinsic lung disease
Cor pulmonale - alteration in structure and function of the right ventricle caused by a primary disorder of the resp system
83
What is forward failure
Heart not pumping enough blood to satisfy all tissues in the body
84
What is backward failure
Not pumping all blood that comes to it
Increased venous pressure
Pulmonary and ankle oedema
Breathlessness from pulmonary oedema
85
What is the vicious cycle of congestive heart failure
Decreased cardiac output
This causes vasoconstriction and fluid retention
This increases preload and afterload which puts stress on the heart
86
Describe persistent ductus arteriosus
Connection between aorta and pulmonary artery
Recirculation of aortic blood
Resultant L --> R shunting
87
Describe atrial septal defects
Flow between atria
L --> R shunting which may eventually switch to R --> L due to RV hypertrophy
E.g. patent foramen ovale
88
Describe atrial septal defects
Flow between atria
L --> R shunting which may eventually switch to R --> L due to RV hypertrophy
E.g. patent foramen ovale
89
Describe ventricular septal defects
Flow between ventricles
L --> R shunting
90
Describe tetralogy of Fallot
Ventricular septal defect
Pulmonary valve stenosis
RV hypertrophy
Resultant R --> L shunting
91
What is coarctation of aorta
Narrowing of aorta in the region of the ductus arteriosus
| Raised upper body BP, normal rest of body
92
What are the two circulations in the body
Systemic and pulmonary
93
Describe primary hypertension
90% of cases
Idiopathic
Risk factors include genetic, diet, chronic stress, RAAS abnormalities, obesity, diabetes
94
Describe secondary hypertension
Less common
| Due to renal disease, endocrine causes or thinks like drugs or coarctation of the aorta
95
What is the difference between benign and malignant hypertension
Benign is slow changes with chronic end organ disease
Malignant is rapid changes in vessels with acute end organ dysfunction - BP tends to be higher
96
What can hypertension affect
Heart - LV hypertrophy, coronary artery atheroma, ischaemic heart disease, cardiac failure
Kidney - nephrosclerosis - proteinuria, chronic renal failure
Brain - intracerebral haemorrhage due to micro aneurysms, stroke
Vascular disease -
- benign - acceleration of atherosclerosis, proliferation and hyalinisation if arteries and arterioles
- malignant - fibrinoid necrosis
- hypertensive retinopathy - haemorrhaging z hard exudates, narrowing of retinal vessels, blindness
97
What is the treatment option for antihypertensives
1st line - A (or B) for young/white and C/D for old or black
2nd line - A+C or A+D
3rd line - A+C+D
Younger and white have more renin so A better
98
What are examples of A antihypertensives
ACE inhibitors (-pril)
Lisinopril, Enalopril, Ranipril
Inhibits angiotensin converting enzyme which prevents conversion of angiotensin I to angiotensin II
Used for hypertension, LV failure, CV event prophylaxis and post MI
Dry cough, hypotension, renal impairment, angioedema
OR
Angiotensin receptor blockers (ARBs) (-sartan)
Losartan, Irbesartan, Candesartan
Antagonises action of angiotensin II
Used in hypertension, diabetic neuropathy, heart failure
Renal impairment, cough (rare), hypotension (rare)
99
Describe beta blockers
(-olol). Atenolol, Bisoprolol (both B1 specific)
Propranolol (non-specific)
Antagonise B1 receptors in the heart to decrease heart rate and contractility
Hypertension, angina, MI, arrhythmias, heart failure
Contraindications - asthma, heart block
Adverse- bradycardia, heart failure, heart block, vasoconstriction, fatigue, erectile dysfunction
100
Describe calcium channel blockers
Amlodipine, Nifedipine
Reduce CA passage into cells to prevent calcium induced calcium release, thus mediating smooth muscle relaxation and vasodilation
Hypertension, angina prophylaxis
Contraindications - heart failure
Flushing, oedema, headache
101
Describe thiazide-like diuretics
Bendroflumethiazide, indapamide
Inhibit Na and Cl reabsorption at the distal convoluted tubule, thereby also decreasing water reabsorption and preload
Hypertension and oedema
Contraindications - gout, lithium treatment
Hyponatremia, hypokalemia, impotence
102
Alpha-1 blockers
(-zosin)
Doxazosin, Terazosin, Prazosin
Antagonise alpha 1 receptors to cause vasodilation and decrease vascular resistance
Hypertension, Raynaud's disease
Contraindications - heart failure, breast feeding
Postural hypotension, dizziness
103
What are some other antihypertensives
K channel openers - minoxidil
Loop diuretics - fusemide
Mineralocorticoid agonists - spironolactone
104
What are antiplatelets
Decrease platelet aggregation
COX inhibitors - block cyclooxygenase which is essential for the production of thromboxane A2 which is a promotor of platelet aggregation
Irreversible - aspirin
Reversible - NSAIDs
Thienopyridines- irreversible platelet ADP receptor inhibitors
Most common is clopidogrel. Prevent ADP from activating GP IIb/IIIa receptor upregulation and therefore platelet adhesion
GP IIb/IIIa antagonist - direct receptor antagonists. Most common are abciximab and tirofiban
Dipyridamole - this drug inhibits the ADP response and upregulates cAMP
105
What is the standard therapeutic strategy for anticoagulants
Rapid initial anticoagulation
Heparin OR
Low molecular weight heparin OR
New oral anticoagulant (dabigitran, rivaroxivan, apixaban)
to reduce risk of thrombus extension or fatal PE
Then extended therapy
Oral vit K antagonist (warfarin) - start immediately and stop heparin once INR 2.0 for two days OR
New oral anticoagulant at lower dose
to prevent recurrance or chronic complications
106
Describe the two types of heparin
Unfractionated - used if risk of bleeding is high as reversible with protamine
Unpredictable due to binding to plasma proteins
Continuous infusion or twice daily administration
Low molecular weight - no need to monitor and 100% bioavailability but irreversible
Once daily dosing
Produced by enzymatic or chemical depolymerization
more predictable
dose dependent renal clearance
Rapid anticoagulation
Binds to antithrombin and increases action
Increased inhibitory action towards factor 10a and thrombin
Use in: DVT, MI, thromboprophylaxis before surgery, PE, coronary artery disease
Contraindications - liver and kidney disease and pregnancy + lactation
Adverse effects- haemorrhage, hyperkalemia (inhibits aldosterone secretion), thrombocytopenia (low platelets)
Osteoporosis can be caused by LMW heparin
107
Describe new oral anticoagulants
Ideal due to lack of monitoring
Apixaban and Rivaroxiban directly inhibit 10a
Dabigitran directly inhibits 2a
Use in DVT, PE, MI, AF to reduce stroke risk
Contraindications - bleeding disorders
Haemorrhage, GI upset
108
Describe warfarin
Cumarin
Constant monitoring as narrow therapeutic window (aim for INR of 2)
Vit K antagonist
Prevents formation of factors 2, 7, 9 and 10
```
takes around 5 days to establish maintenance dosing
loading regimens assist early dosing
individual dose for each patient
dietary vit K intake affects dose
many drug interactions
```
DVT, PE, AF, prosthetic valves
Haemorrhagic stroke, significant bleeding
Adverse effects - haemorrhage, nausea, vomiting, diarrhoea, liver problems
109
What is used to increase myocardial contractility
Digoxin (ACUTE)
cardiac glycoside
Blocks Na/K ATPase
Slows AV conduction
Increased cardiac contractility
Used for atrial fibrillation or heart failure
requires loading dose
Contraindications - renal failure, hypokalemia
Adverse effects - hypokalemia, anorexia, nausea, vomiting, visual disturbances, AV block, arrhythmias
Dobutamine
110
What is used to inhibit sympathetic activation?
Beta blockers
111
What is used to inhibit the renin- angiotensin system
ACE inhibitors
Angiotensin II receptor blockers
Mineralocorticoid receptor antagonists
112
What is used to reduce preload
Loop diuretics
113
What is used for vasoconstriction
```
Nitrovasodilators
- glyceryl trinitrate - breaks down to nitric oxide
Used in angina or heart failure
Contraindications - aortic stenosis
Adverse effects- headache, dizziness
```
Hydralazine
Direct vasodilator
Headache, tachycardia, palpitations
114
What are class 1b antiarrhythmics
Na channel clockers such as Lidocaine
Used for SVT, VF and post MI
115
What are class II antiarrhythmics
Beta blockers such as atenolol
Used in AF, hypertension and angina
116
What are class III antiarrhythmics
K channel blockers such as amiodarone
Used in AF, SVT, VF
117
What are class IV antiarrhythmics
Calcium channel blockers such as verapamil
Used in AF, SVT, Angina
118
What are class V antiarrhythmics
Na/K ATPase inhibitors such as digoxin
Used in AF and heart failure
Or adenosine for diagnosis of SVT
119
What can be used to treat atrial fibrillation
Atenolol, amiodarone, verapamil, digoxin
120
What can be used to treat SVT
Adenosine for diagnosis.
Lidocaine, amiodarone, verapamil
121
What can be used to treat VF
Lidocaine, amiodarone
122
Describe adenosine
Agonist at A1 AV node receptors
Hyperpolarisation of conduction tissue
transient blockage of AV node
Indications - SVT
Contraindications - kidney failure, hypokalemia
Adverse effects- dyspnoea, nausea, dizziness
123
Describe amiodarone
Very long half life
Blocks K channels
Prolonged action potential
Treats all arrhythmias
Contraindications- bradycardia, heart block, thyroid dysfunction
TOXIC
124
Describe lidocaine
Blocks Na channels
Stops membrane depolarisation
SVT, VF, post MI
Nervous system and cardiovascular depression
125
Describe verapamil
Calcium channel blocker
Specific to L-type channels
Decreased cardiac conduction and contractility due to reduced conduction in AV and SA nodes
AF, SVT and angina
Constipation, heart block, bradycardia
126
What is the third heart sound?
Early diastole in young trained athletes
Ventricular gallop
Return in later life indicates abnormality
127
What is the ejection fraction
Amount of blood pumped out. 55-60% usually
| 80% in exercise
128
What is the starling law if the heart
The more blood in the heart the more the muscle fibres are stretched (within limit) - more force of contraction - more blood pumped out
129
What will the ECG show if the impulse runs away from it
Negative
And positive if towards
130
How long should each part of the ECG be
PR - 0.12-0.2 secs
QRS - <0.12 secs
QT - <0.44 secs men and 0.46 secs women
131
How do you calculate heart rate
If regular
300/number of large squares between R waves
If irregular
Number of QRS complexes x 6
132
What are the types of heart block
1st - regular, PR interval more than 0.2s
2nd (mobitz I) - irregular, PR continues to lengthen until a QRS is missed
2nd (mobitz II) - irregular, QRS may be wide, non conducted sinus impulses appear at irregular intervals - treatment is a pacemaker
3rd- atria and ventricles beat independent of each other, usually requires pacemaker
133
What do you call a clot which isn't a thrombus?
Haematoma
134
What's the difference between superficial and deep venous thrombosis
Deep is often asymptomatic - only recognised when they have embolised such as to the lungs
Superficial - swelling, pain, tenderness (rarely embolise)
135
How is an embolus determines post death?
If it is not the same calibre as the vessel it gets stuck in
Will be the diameter of the vein it came from
136
What is a paradoxical embolism?
When a embolus causes a stroke due to getting into the left side of the heart due to interatrial or interventricular defect
137
When is homocysteine measured
In young patients with CV disease in the absence of usual risk factors
138
What is troponin
1:1:1 of three regulatory proteins TnT, TnI and TnC
Exclusively present in striated cells
cTnI and cTnT are cardiac forms
139
What are ANP and BNP
Atrial natriuretic peptide and brain natriuretic peptide
Promote vasodilation and natriuresis
Raised in heart failure
140
What may a large QRS complex mean?
Hypertension as the ventricles are thicker than normal
141
What may a thick QRS complex mean?
May indicate a problem with conduction through the bundle if His
142
What are pathological causes of sinus bradycardia
Hypothyroidism, hypothermia, sinus node disease, raised intercranial pressure as brainstorm gets pushed down through the foramen magnum - leads to headache and vagus nerve activation - very slow heart rate
143
What are some causes of AV nodal block
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Sino-atrial disease
Coronary heart disease
Aortic valve disease
Damage during heart surgery
Beta blockers
Digoxin
Calcium channel blockers
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Treatment - remove triggering cause, atropine or isoprenaline (acute treatment)
Permanent treatment - pacemaker
144
Causes of atrial flutter/fibrillation
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Sino-atrial disease
Coronary heart disease
Valve disease
Hypertension
Cardiomyopathy
Hyperthyroidism
Pneumonia
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145
What is preload increased
SNS activation
Heart failure
Renal failure
Determined by blood volume and venous tone (capacity of venous circulation to hold blood)
146
What is afterload increased by
SNS activation
Hypertension
Determined by tone in arterial circulation
147
What does vascular endothelium regulate?
Blood vessel tone
Permeability
Leukocyte adhesion, platelet aggregation and tendency for thrombus formation
148
What is endothelial dysfunction caused by
High LDL
Oxygen free radicals caused by smoking, hypertension activation inflammatory cells
Infectious microorganisms
Physical damage and gene activation by turbulent flow HIGH BP
Diabetes
Ageing
Being male (women protected by oestrogen until menopause)
149
What do statins do
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Lower LDL by increasing expression of LDL receptors
Improve endothelial function
Inhibit inflammation
Stabilise plaques
Inhibit thrombus formation
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150
What do fibrates do
Activate PPAR alpha
| Decreases VLDL and triglycerides and increase HDL
151
What does ezetimibe do
Lowers cholesterol absorption from gut
152
What is the treatment of angina
Increasing supply which is decreased by coronary artery disease and anaemia
Or
Reducing demand which is increased by exercise, tachycardia or hypertension
153
How do you reduce demand on the heart
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Acute - glyceryl trinitrate
Sublingual
Rapid acting
Chronic use leads to tolerance
Inhibits guanylate cyclase which reduces availability of Ca for contraction
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Prophylactic- isosirbide dinitrate
Oral
Longer lasting
Dilates veins to reduce preload
Or
K atp channel opener such as nicorandil
Causes blood vessel dilatation by opening ATP sensitive K channels in smooth muscle cells
154
What do beta blockers do
Block renal beta 1 adrenoreceptors - reduce blood volume by reducing renin release and activation of RAAS reduce preload and therefore O2 demand
Blocks cardiac beta 1 adrenoreceptors - reduced heart rate and therefore O2 demand
155
What does ivabradine
Blocks funny current in sino atrial cells - reduces heart rate
Less side effects than beta blockers - used as alternative or adjunct
156
What do calcium channel blockers do
Reduce force of contraction by preventing opening of voltage dependent Ca channels
157
What is the difference between congenital and acquired haemophilia
Congenital
Haemarthroses
Muscle bleeds
Soft tissue bleeds
Acquired
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Large haematomas
Gross haematuria
Retropharyngeal and retroperitoneal haematomas
Cerebral haemorrages
Compartment syndromes
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158
What is tranexamic acid
An antifibrinolytic for the treatment of bleeding disorders
159
Describe DIC
Acquired syndrome of intravascular activation of coagulation
Widespread deposition of fibrin
Tissue ischaemia and multiple organ failure
Consumption of platelets and coagulation factors can induce severe bleeding
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Can be caused by;
Sepsis
Tumour
Trauma - fat embolism, burns, lightning strike
Pancreatitis
Obstetric - amniotic fluid embolism, pre-eclampsia, eclampsia
Kasabach Merritt syndrome
Aortic aneurysm
Toxic
Transfusion of incompatible blood
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Prolonged prothrombin time and APTT as well as low fibrinogen are markers if consumption of coagulation factors
160
What do PCSK9 inhibitors do
What do you think?
PCSK9 destroys LDL receptors
161
Describe direct oral anticoagulants
Treatment of DVT and PE
Prevention of cardioembolic events in atrial fibrillation
More predictable, less interactions, wider therapeutic window and simpler dosing than warfarin
162
What is HF with reduced ejection fraction
Impaired contractility and emptying of ventricle - more common
163
What is HF with preserved ejection fraction
Impaired relaxation and filling of ventricle
164
What controls venous return
Muscle pumps, thoracic pump action during respiration, right heart action, functioning valves
165
How much urine does the kidney produce
Filters 125ml/min and produces around 1ml of urine
166
What are the consequences of cardiac arrhythmias?
Altered heart rate (usually too fast)
Reduced ventricular filling, cardiac ejection and efficiency
Lower blood pressure, heart failure, angina, death
