Anatomy - Atrial Fibrillation Flashcards
(122 cards)
1
Q
What are the locations of the spontaneously firing cells in the heart?
A
2
Q
What are the spontaneous discharge rates in the heart?
A
SA node = 70-80 action potentials/min
AV node = 40-60 action potentials/min
Purkinje = 20-40 action potentials/min
Fastest drive heart, hence SA node
3
Q
What does the action potential graph of a pacemaker cell look like?
A
4
Q
What is the route of excitation spread through conducting tissue?
A
- SA node (pacemaker)
- Rapidly through the atria (~ 1m/sec)
- AV node (slow conducting ~ 0.05m/sec - delay)
- Rapidly through bundle of His & down the bundle branches & Purkinje fibres (~ 1-4m/sec)
- Through ventricular muscle cells
5
Q
What aids the rapid spread of excitation in heart?
A
Intercalated discs between fibres
Gap junctions, providing low resistance pathways
6
Q
How is the spread of excitation coordinated in atria and ventricles?
A
Atrial excitation and contraction are complete before ventricular contraction –> enables efficient emptying of blood from atria to ventricles
Ventricular excitation occurs synchronously –> enables ventricles to contract as coordinated units, expelling blood effectively
7
Q
What does the action potential graph of ventricular cell look like?
A
8
Q
What does excitation-contraction coupling require?
What are the order of events?
A
Calcium
- Influx of Ca2+ during action potential
- Triggers release of further Ca2+ from sarcoplasmic reticulum
- Free Ca2+ activates contraction of myocardial fibres (SYSTOLE)
- Amount of Ca2+ determines cross-bridge cycling & force of contraction
- Uptake of Ca2+ by sarcoplasmic reticulum and extrusion of Ca2+ by Na+/Ca2+ exchange and outward Ca2+ pump
- Lowers free Ca2+ allowing relaxation (DIASTOLE)
9
Q
What is the function of the plateau phase during heart contraction?
A
Protects heart from tetanus
Provides long refractory period
10
Q
What is the direction of ventricular excitation?
A
Endocardium to epicardium
Apex to base
11
Q
What does activation of sympathetic nerves do to the heart?
What does the graph look like?
A
Increases heart rate by activating ‘beta’1-adrenoceptors in sino-atrial node
12
Q
What does activation of parasympathetic nerves do to the heart?
What does the graph look like?
A
Decrease heart rate by activating M2 muscarinic receptors in sino-atrial node
13
Q
What 5 things does an ECG provide?
A
- Timing and direction of cardiac events –> atrial and ventricular depolarisation, ventricular repolarisation
- Rate/rhythm disturbances –> tachycardia/bradycardia, sinus rhythm, arrythmia
- Conduction abnormalities –> A-V conduction time
- Mass of active myocardium –> ischaemic areas
- Nothing about mechanical force, only electrical conduction
14
Q
What is the difference between indifferent (negative) and unipolar (positive) electrodes?
A
- = measure average
+ = measure from cells closest
15
Q
What does depolarisation do to the polarity of a cell?
What happens with depolarisation towards and away from positive electrode?
A
Inside = positive
Outside = negative
Towards = upward deflection on ECG trace
Away = downward deflection on ECG trace
16
Q
What happens when electrode is perpendicular to depolarisation?
What happens during depolarisation towards and away from negative electrode?
A
No change on ECG trace
Towards = downward deflection on ECG trace
Away = upward deflection on ECG trace
17
Q
What is the relationship between electrodes on an ECG trace?
What is a bipolar potential?
A
Focally positioned negative electrode = records same as diametrically opposite positive electrode
Both positive and negative
Composite of what + and - electrodes measure
Longer line on ECG trace
18
Q
What does repolarisation do to a cells polarity?
What are the principles of repolarisation?
A
Inside = negative
Outside = positive
Reverse principle of depolarisation
19
Q
What is the recorded potential difference?
A
Mean vector of different wavefronts
Excitation = depolarisation moves in different directions
20
Q
What are the 3 main events of the cardiac cycle?
A
- Atrial depolarisation
- Ventricular depolarisation
- Ventricular repolarisation
21
Q
What happens during the P wave?
A
Atrial depolarisation
At bottom of peak, all cells are repolarised
22
Q
What happens during P-Q?
A
Septum depolarisation
Small negative
Generally away from electrode
23
Q
What happens during QRS?
A
Main ventricular depolarisation
Large positive
Towards electrode
24
Q
What happens during S-T?
A
Base of ventricle depolarisation
Small negative
Away from electrode
25
What happens during T wave?
Ventricular repolarisation
Positive
Away from electrode
26
Where do the unipolar limb leads measure?
27
Where do the unipolar chest leads go?
4th intercostal space at right sternal margin
5th intercostal space at mid-axillary line
V1-V6
28
Where are bipolar limb leads placed and how do you get the actual measurement?
Left = positive electrode
Right = negative electrode
Actual measurement = between 2 positive electrodes
29
What are the 2 different ways an ECG can present?
30
What are the 6 rules to remmeber about ECG traces?
* The first wave, irrespective of its polarity, is always called a P wave
* The final wave is called a T wave (unless U waves (rare) are present
* The first positive wave after a P wave is called an R wave
* Any negative wave after a P wave but before an R wave is called a Q wave
* Any negative wave after an R wave is called an S wave
* Any positive wave after an S wave is called R'
31
What are the durations of all of the different ECG waves?
* P duration = 0.08s
* P-R interval = \<0.2s
* QRS = 0.1s
* ST length = ejection
* T-P interval = filling
32
What does it mean when QRS complex has left or right axis deviation?
33
What are the different types of heart block?
* 1st degree = long P-R
* 2nd degree = some P with no QRS
* 3rd degree = complete block = no A-V conduction
34
What is tachycardia and what does it look like on ECG?
Atrial or ventricular
35
What does atrial fibrillation look like on ECG?
Ventricular = requires defibrillation or death
36
What are the different types of anaemia?
–Iron deficiency anaemia
–Megaloblastic anaemia
–Haemolytic anaemia
–Aplastic anaemia
–Sickle cell
–Thalassaemias
37
What are the symptoms of anaemia?
* Reduced Hb levels
* Shortness of breath
* Weakness/lethargy
* Tachycardia
* Pale nail bed and conjunctiva
* Severe elderly may cause angina
* Glossitis (painful red tongue)
* Angular cheilitis (fissures at corner of mouth)
* RBC DPG elevated
38
What are the causes of anaemia?
* Reduced input --\> poor diet, stomach removal
* Increased output --\> menstruation, GI bleeding ulcers, colon cancer
* Increased demand --\> pregnancy
39
What are the treatment options for anaemia?
* Find and treat underlying cause
* Oral iron
* Prophylaxis in pregnancy
* Transfusion
40
What are the properties of renal anaemia?
* Complicates CRF
* Leads to normocytic anaemia
* Treat with Fe and EPO
41
What are the properties megaloblastic anaemia?
* Abnormal RBC maturation from defective DNA synthesis (bone marrow contains megaloblasts)
* Macrocytic
* Due to vitamin B12 or folate deficiency
* Jaundice
* B12 = required for cell division --\> from animal products
42
What are the properties of folic acid?
* Folate = essential for thymidylate synthesis (rate limiting step in DNA synthesis)
* Found in most foods (greens, liver, yest, marmite)
* Used in pregnancy
43
What is the function of methotrexate?
Inhibits dihydrofolate reductase
Impaired folate regeneration
Treated with folinic acid
44
What is pernicious anaemia?
Lack of intrinsic factor for B12 absorption due to autoimmune disease
Treat with hydroxocobalamin
45
What is Chron's disease?
Malabsorption of B12, folate or iron
46
What are the properties of haemolytic anaemias?
* Increased rate of RBC destruction
* Spherocytosis - genetic - abnormal reduction in RBC membrane protein (spectrin) - cells fragile
* Acquired - haemolytic transfusion reaction, malaria, drug-induced
* Jaundice (?) and enlarged spleen - folate deficiency may occur due to increased erythropoiesis
47
What are the properties of sickle cell anaemia?
•Genetic
* SNP: Single Nuleotide Polymorphism
•Amino-acid substitution
* Valine for glutamic acid
* Abnormal Hb - insoluble forms crystals at low O2 - RBC form sickle shapes and may block microcirculation.
* Causes haemolytic anaemia
48
What are the properties of thalassaemias?
* Genetic
* Reduced rate of 'alpha' or 'beta' globin units production many variations
* Deletion of both a-genes leads to death in uterus as Hb ('gamma'4) produced
* One 'alpha'-gene deletion reduced RBC volume and haematocrit
49
What are the properties of aplastic anaemia?
* Insufficient production of RBCs, WBCs and platelets (pancytopenia) - although may just be RBCs (pure red cell aplasia)
* Deceased resistance to infections, increased bleeding, increased tiredness
* Mostly acquired : viral, radiation or drugs
* Cytotoxic (anticancer) agents
* Chloramphenicol
* Sulphonamides
* Insecticides
50
How do you treat aplastic anaemia?
* Bone marrow transplant - with tissue match
* Immunosuppressants - to prevent immune destruction of stem cells
* Colony-stimulating factors - increase WBC count
51
What is polycystaemia and what is it caused by?
* Increased Hb content and haematocrit (\>55 in males and \>47 in females)
* Increased blood viscosity - poor tissue perfusion
* Primary: Changes in bone marrow, stem cell defect
* Secondary: Increased erythropoietin - altitude, smoking, renal carcinoma
52
What are the signs and symptoms of polycythaemia?
–Ruddy appearance
–Cyanosis: sluggish blood flow leads to greater deoxygenation
–Headaches
–Blurred vision
–Hypertension
53
How do you treat primary polycythaemia?
* Venesection (bleeding)
* Radioactive Phosphorus - myelosuppression
* Cytotoxic agents - myelosuppression
54
What are all these parts?
55
What are the stages of heart development?
* Linear heart tube formation
* Formation of cardiac loop
* Heart septation
* Cavitation of ventricle
* Formation of valves and great vessels
* 4-chambered heart
56
What are each of these parts?
57
What are each of these parts?
58
How does the cardiac loop form?
59
What are the benefits of X-rays?
* Quick and inexpensive examination
* Good for initial examination for assessing lungs and bones
* Low radiation dose
60
What are the drawbacks of X-rays?
* Uses ionising radiation
* Limited spatial information
* Poor examination for soft tissue pathology
61
What are the benefits of CT?
* Relatively quick scanning time of large areas of the body
* Provides very good anatomical information in multiple planes
* Appropriate to assess for most acute clinical problems
62
What are the drawbacks of CT?
* Can involve large doses of ionising radiation
* Risk of allergy to iodine-based contrast
* Particularly poor at assessing the spinal cord and reproductive organs
63
What are the benefits of fluoroscopy?
* Dynamic real time anatomical assessment
* Commonly used for interventional procedures
* Low radiation dose
64
What are the drawbacks of fluoroscopy?
* Doses for complex IR procedures can be large
* Always requires use of contrast agents
* Poor soft tissue assessment and overlapping anatomy
65
What are the benefits of MRI?
* Does not use ionising radiation
* Excellent anatomical detail
* Multiple phases enable some functional assessment of tissues
66
What are the drawbacks of MRI?
* Time consuming and expensive
* Safety issues regarding metallic implants
* Claustrophobic
67
What are the benefits of ultrasound?
* Dynamic study allowing real time assessment
* Does not involve ionising radiation
* Modality of choice for paediatric and antenatal imaging
68
What are the drawbacks of ultrasound?
* Poor assessment of air-filled structures and bone
* More heavily operator/patient dependent
* Attenuation of sound waves limits scan depth
69
What are the benefits of nuclear medicine?
* Large number of tracers available to assess different tissues
* Provides anatomical and functional information
* Usually allows more definitive assessment of pathology identified on other modalities
70
What are the drawbacks of nuclear medicine?
* Scan acquisition is time consuming
* Poor resolution compared to alternative cross-sectional imaging
* Radiation exposure continues after termination of examination
71
What is the radiation law?
* Ionising Radiation Regulations (IRR)
* Protection of employees against exposure to ionising radiation as a result of work activities
* Ionising Radiation Medical Exposure Regulations (IRMER)
* Intended to protect patients from the hazards associated with ionising radiation
* ALARP Principle
72
What are the 2 coagulation pathways and what causes them to occur?
_Intrinsic coagulation pathway_ --\> occurs due to exposure to collagen from injured blood vessel wall or test tube
_Extrinsic coagulation pathway_ --\> occurs due to damaged tissue releasing thromboplastin
73
What are the properties of platelets?
* Non-nuclear cellular fragments
* Form mechanical plugs during blood vessel injury
74
What happens during adhesion and aggregation reactions with platelets?
* Adhesion and aggregation reactions:
* Adhesion: to subendothelial surface on damage/disease - due to binding to Von Willebrand’s factor
* Adhesion causes Release reaction: ADP and thromboxane which promote platelet Aggregation
* Leads to platelet mass to plug area of endothelial damage - promotes coagulation reaction: -vely charged phospholipids on activated platelets which have adhered to site of damage localize fibrin formation
* Coagulation involved in: Haemostasis - stopping blood loss through damaged vessels
75
What are the 3 laboratory tests for platelet and coagulation and how are they carried out?
_Bleeding time_
* Incisions to forearm with venous cuff
* Increased in platelet dysfunction/thrombocytopenia
_Prothrombin time [INTERNATIONAL NORMALISED RATIO: INR]_
* Time for coagulation following addition of thromboplastin.
* Prolonged by abnormalities of Factors VII, X, V, II or I, liver disease or warfarin
_Activated partial thromboplastin time (APTT)_
* Examines ‘intrinsic pathway’
* Altered by changes in Factors XII, XI, IX, VIII, X, V, II or I
76
What are 3 clotting and bleeding disorders?
* Thrombosis - unwanted blood clots
* Venous: clots (thrombi) form in veins (DVT) due to stasis of blood, may travel to lungs PULMONARY EMBOLISM.
* ‘Economy class syndrome’
* Atrial fibrillation: risk of TIA (transient ischaemic attack) or stroke
77
What is atrial fibrillation, associated risks and treatment?
Random electrical impulese leading to irregular atrial contraction
Lack or coordinated heartbeat
Risk = cardioembolic stroke
Treatment = anti-coagulants
78
What are the properties of arterial thombosis?
* Form at atherosclerotic sites
* Lead to arterial blockage
* MI and stroke
79
What is the difference between venous and arterial thrombosis?
Venous = more of a coagulation factor event, i.e. DVT
Arterial = more of a platelet event, i.e. stroke, MI
80
What is the atherosclerosis timeline?
81
What is haemophilia A and how do you treat it?
* Genetic - carried on X-chromosome, so males (XY) most affected and females (XX) carriers
* Low or lacking Factor VIII of the clotting cascade
* Haemorrhage and prolonged bleeding (e.g. after tooth extraction)
* Treat with Factor VIII from blood donors or analogue of vasopressin (ADH) which increases patients Factor VIII release
82
What is haemophilia B and how do you treat it?
* Deficiency of Factor IX
* Treated with prophylactic Factor IX
83
What is emicizumab used for and how is it administered?
* For Haemophilia A
* Monthly sc injections as opposed to daily infusions of Factor VIII
* Bispecific MAB: binds to activated Factor IX and X
* Very effective at reducing bleeds
* 30% of pts with Haemophilia A treated with Factor VIII develop resistance due to inhibitory factors produced
84
What is Von Willebrand's disease?
* Hereditary lack or defect in vWF
* Leads to increased bruising, nose bleeds, mucosal bleeding
* Rx: analogue of vasopressin (ADH), factor VIII or vWF
85
What happens in liver disease in relation to coagulation etc.?
* Reduced synthesis of clotting factors leads to increased bleeding
* Increased Prothrombin time
86
What is thrombocytopenia and what is it caused by?
* Reduced platelet number
* Spontaneous skin bleeding (purpura)
* Causes:
* Idiopathic
* Viral
* Drug-induced --\> treat with steroids if unresponsive splenectomy
* Toxins
87
What is disseminated intravascular coagulation and how is it treated?
* Large amounts of fibrin generated by procoagulant material such as amniotic fluid
* Vast consumption of clotting factors and platelets
* Widespread haemorrhage but may also be thrombosis
* Give platelets and fresh frozen plasma
88
What is factor V Leiden mutation?
* Abnormal Factor V
* Single nucleotide polymorphism
* Less susceptible to deactivation
* Increases risk of venous (but not arterial) thrombosis
* Esp with oral contraceptives/pregnancy
89
What is an ischaemic stroke and the different types?
* Caused by blockage of blood flow to brain - 85% of all strokes
* Thrombotic and embolic
* Small vessel disease = lacunar stroke (20%)
* Large artery atherosclerosis (20%)
* Cardioembolic stroke = caused by atrial fibrillation (25%)
* Cryptogenic stroke = no known causes (35%)
90
What is a mini stroke?
* Transient ischaemic attack
* No permanent disability
* Lasts up to 24 hours
91
WWhat is a haemorrhagic stroke and the types?
* Caused by artery in ,or to, brain rupturing
* Intracerebral haemorrhage = 85%
* Subarachnoid haemorrhage = 15%
92
What are the 4 types of atrial fibrillation and their properties?
* **Paroxysmal AF**
* Episodes come and go and usually stop within 48 h without any treatment
* **Persistent AF**
* Each episode lasts for longer than seven days (or less when it's treated)
* **Long-standing persistent AF**
* Continuous AF for a year or longer
* **Permanent AF**
* AF is present all the time
93
What are causes of atrial fibrillation?
* Hypertension
* Atherosclerosis
* Congenital heart disease
* Cardiomyopathy
94
What are treatments for atrial fibrillation?
* Medicines to reduce the risk of a stroke
* Medicines to control AF (beta-blockers, anti-arrythmics)
* Cardioversion (electric shock treatment)
* Catheter ablation (electrocardiology)
* Having a pacemaker fitted
95
How do you diagnose a stroke?
* Physical examination – medical history
* Neurological examination
* Radiological examination (imaging via CT or MRI)
* Check BP, HR and cholesterol
* Right cerebral hemisphere à visual awareness, spatial awareness, proprioception, memory, recognition
* Left hemisphere à language, analytical thinking, mathematical skills
96
How do you determine stroke prognosis?
* Location of the brain damage
* Size of the brain damage
* The presence of other medical conditions
* Possibility of stroke recurring
97
What are the treatments for ischaemic stroke?
* Recombinant tissue plasminogen activator (rt-PA) – short therapeutic window (4.5 h of stroke onset)
* Mechanical thrombectomy (physical removal of blood clot from the larger arteries)
* Carotid endarterectomy – surgery to remove carotid plaque
98
What are the treatments for haemorrhagic stroke?
* No medical therapy - treat hypertension
* Surgery to stop or prevent bleeding
99
What are alternative stroke treatments?
* Hypothermia --\> intravascular cooling, surface cooling
* Cellular treatment --\> stem cells, endothelial progenitor cells
100
What is warfarin and how does it work?
* Oral anticoagulant
* Vitamin K antagonist
* Vitamin K essential for production of prothrombin and Factors VII, IX and X (Vitamin K important for post-ribosomal carboxylation of glutamic acid residues of these proteins)
* Warfarin blocks Vitamin K reductase, needed for Vit K to act as a cofactor (Vitamin K Epoxide Reductase Complex, VKORC)
* Prevents thrombosis
101
Who takes warfarin and what can increased drug action lead to?
* Patients with replaced valves, atrial fibrillation, PE, DVT
* Takes several days to act
* Dose = determined by international normalised ratio (INR)
* Has many drug interactions
* Increased actions = gastric bleeding, cerebral bleeding, haemoptysis, blood in faeces, blood in urine and easy bruising
102
What is heparin and how does it work?
* Injectable anticoagulant
* Activates antithrombin lll
* Antithrombin = complexes with serine protease of factors to inactivate some clotting factors and thrombin
* Immediate action
* Prevents thrombosis
* Used while warfarin takes effect
* Unfractionated heparins monitored vie APTT
103
What are DOACs?
* Direct oral anticoagulants
* Dabigatran = oral thrombin inhibitor
* Prevents thromboembolism --\> less bleeding than warfarin, fewer drug interactions, no monitoring required
104
What is prostacyclin and how does it work?
* Endothelial-derived vasodilator
* PGI2
* Prevents platelet aggregation by acting on platelets to increase cAMP
* Thromboxane = TXA2 = promotes aggregation, decreases cAMP
105
What is nitric oxide and how does it work?
* Endothelial-derived vasodilator
* L-arginine + O2 --\> NO + citrulline by nitric oxide synthase
* Nitric oxide - prevents both platelet adhesion and aggregation by increasing platelet cGMP
106
What is aspirin, who is it for and how does it work?
* Antiplatelet drug
* Low dose aspirin (75mg)
* Prevents MI in patients who have previously had an MI
* Not recommended for primary prevention
* Reduces stroke incidence
* Inhibits cyclo-oxygenase (irreversible)
* Favours PGI2 production over TXA2 --\> platelets have no nuclei, no COX produced, no TXA2 until new platelets synthesised --\> endothelial cells have nuclei, produce COX, PGI2 produced
107
What is dipyridamole and how does it work?
* Antiplatelet drug
* Phosphodiesterase inhibitor - prevents cAMP and cGMP breakdown - cAMP to AMP
* Prevents thrombosis
* Inhibits adenosine uptake
* Used in conjunction with aspirin
108
What is the role of GP llb/llla?
Binds to fibrinogen, leading to cross-linking of platelets
109
What is clopidogrel?
* Inhibits ADP-induced expression of GP
* For those who can’t take aspirin
* Same effectiveness as aspirin
110
What is abciximab?
* Monoclonal antibody against GP llb/llla
* Given to those undergoing angioplasty
* Only used once
111
What is fibrinolysis and how does it work?
* i.e. alteplase
* Endogenous system to dissolve clots
* Activated parallel to clotting system
* Plasminogen --\> plasmin
* Plasmin = digests fibrin of clot
* Fibrinolytic agents = activate plasminogen to plasmin conversion
112
What are thrombolytics and when are they used?
* Given immediately after MI à dissolve thrombus causing MI
* Used for PE too
* Best with aspirin (can cause bleeding) --\> not used after surgery, haem stroke, ulcers
* Used in thromboembolic stroke
113
What are the properties of drug interactions and what affects them?
* + toxicity or reduced activity
* Problem for drugs with small therapeutic window
* Increased by conditions, i.e. renal impairment
* May be beneficial or adverse
* Food can have impact
114
What strategies can you use to combat drug interactions?
* Avoid
* Alternatives
* Reduce dose
* Monitor patient
115
What is the process of drug interaction absorption?
* 2 drugs interact and alter rate of uptake
* ATP binding cassette / multiple drug resistance transporter
* Drugs can induce or inhibit it
* Digoxin is substrate and induction of MDR1 reduces bioavailability
116
What is drug displacement?
* + drugs protein bound, only act in free form
* A result of drugs competing for binding sites
117
What are the 2 CYP450-mediated metabolism processes?
Inhibition or induction
+ drugs metabolised by multiple CYPs
118
What are the properties of CYP enzyme inhibition?
* Antifungals, macrolide
* Rapid 1-2day onset
* Reverse quickly when stopped
119
What happens when warfarin INR increases?
+ bleeding risk
120
What happens when NSAIDs and warfarin interact?
* + interactions
* Aspirin = antiplatelet, so + bleeding effects
* NSAIDs associated with gastric bleeding, + with warfarin
121
What are the 4 main drug interactions to remember?
Warfarin and NSAIDs = leading to enhanced bleeding
Warfarin and antibiotics (esp erythromycin and ciprofloxacin) = leading to enhanced bleeding
Simvastatin and macrolides = avoid
Simvastatin and amlodipine = caution dose
122
What are the causes of different patient responses to therapy?
* Metabolism
* Renal function
* Interactions
* Resistance
* Pharmacogenetics
* Genetic differences in pharmacokinetics
* Genetic differences in pharmacodynamics
* Ethnicity
