PBL Topic 2 Case 5 Flashcards
Identify two adhesion molecules involved in the development of an atheroma
- ICAM-1
- E-Selectin
What causes expression of adhesion molecules in the development of an atheroma?
- Damage to the vascular endothelium
- For example increased blood pressure
What is the effect of adhesion molecules in the development of atheroma?
- Decrease nitric oxide release
- Increased adhesion of particles
Identify how foam cells are produced and explain their effect in the development of an atheroma
- Adhesion of monocytes and LDLs
- Differentiation of monocytes into macrophages
- Macrophages engulf LDL to form foam cell
- Which form a visible fatty streak
How does the formation of a visible fatty steak result in vessel occlusion?
- Proliferation of fatty streak to form a plaque
- Plaque bulges into lumen
How does hardening of the arteries occur in atherosclerosis?
- Fibroblasts deposit connective tissue
- Calcifications
Explain how the presence of the plaque may result in thrombus or embolus formation
- Rupturing of plaque causes rough surface
- Which attracts platelets
- Deposition of fibrin
- Trapping of red blood cells
How is cholesterol transported from the liver?
- As low density lipoproteins
- Composed of 50% cholesterol and 20% protein
How is cholesterol transported back to the liver?
- As high density lipoproteins
- Composed of 50% protein and 20% cholesterol
Explain the process by which cells take up cholesterol
- Receptor Mediated Endocytosis
- LDL binds to receptors
- Clathrin coated pits pinch off to form clathrin coated vesicles
- Vesicles are delivered to endosomes
Identify five risk factors for atherosclerosis
- Hypertension
- Familial Hypercholesterolemia
- Smoking and Alcohol Consumption
- Diet and Physical Inactivity
- Family History
What is an aneurysm?
- Permanent dilation of a vessel
- Due to loss of elastic tissue
Where are atherosclerotic aneurysms typically located?
- Lower abdominal aorta
- Iliac arteries
What are the clinical effects of atherosclerotic aneurysms?
- Pulsatile abdominal mass
- Lower limb ischaemia
- Rupture, with massive retroperitoneal haemorrhage
When does ischaemia occur?
- When there is an imbalance between the supply of oxygen and the metabolic demands of the tissues
Identify three causes of ischaemic heart disease
- Atherosclerosis
- Shock
- Stenosis
When does coronary heart disease develop?
- When the vessel is more than 75% occluded
When does reversible ischaemia of coronary vessels develop?
- When ATP levels are low and anaerobic glycolysis has ceased
When does angina occur?
- Lack of blood supply
- Results in lack of contractility
Identify three characteristics of stable angina
- Central chest pain
- Precipitated by exertion
- Relived by rest
Identify two characteristics of angina on an ECG
- ST depression
- T wave inversion
Identify five pieces of lifestyle advice for a patient suffering from angina
- Smoking cessation
- Regular exercise
- Avoiding severe unaccustomed exertion
- Aim for ideal bodyweight
- Sublingual nitrates
Identify an example of a potassium channel activator
- Nicorandil
Identify three examples of calcium channel antagonists
- Nicardipine
- Nifedipine
- Verapamil
- Diltiazem
Explain the mechanism of action of calcium channel antagonists
- Inhibit L-type calcium channels
- Reducing myocardial contractility and blood pressure
- Reducing oxygen demand of myocardium
Identify three side effects of calcium channel antagonists
- Flushing
- Peripheral Oedema
- Headache and Dizziness
Identify an example of an If channel antagonist and explain its effect
- Ivabradine
- Induces bradycardia by modulating ion channels in the sinus node
When is PCI carried out?
- Single vessel disease
- Multi-vessel < 65 years
- Suitable anatomy
Outline the procedure of PCI
- Guidewire passed across stenosis
- Ballon inflation to dilate stenosis
- Stent insertion to maximise dilation
Identify three drugs that are combined with PCI to improve patient outcome
- Aspirin
- Heparin
- IIB/IIIa Receptor Antagonists
Identify two examples of drug-eluting stents
- Cypher Stent, contains sirolimus, an immunosuppressant agent
- Taxus Stent, contains paclitaxel, a mitotic inhibitor
Identify the main complication of PCI
- Occlusion
Outline the evidence base of PCI
- Stents (drug-eluting) result in lower rates of stenosis
- More effective in alleviating angina than medical therapy
- Does not reduce mortality
- Carries risk of procedure-related MI
When is CABG carried out?
- Unsuitable anatomy
- Multi-vessel > 65 years
- Diabetes
Outline the procedure of CABG
- Bypassing coronary stenosis
- Using internal mammary arteries, radial arteries of reversed segments of saphenous vein
Identify three drugs that are combined with CABG to improve patient outcome
- Aspirin
- Clopidogrel
Which type of graft is more patent following surgery?
- Arterial grafts
Outline the evidence base of CABG
- Superior to medical treatment in terms of survival
- Most effective in left main coronary artery
- Reduced need for repeat procedure compared to PCI
- Better survival rates in patients with diabetes compared to PCI
Briefly outline unstable angina
- Deterioration of stable angina
- Symptoms occurring at rest
Briefly outline refractory angina
- Revascularisation is not possible
- Angina is not controlled by medical therapy
Briefly outline variant (Prinzmetal’s) angina
- Angina without provocation
- Characteristic ST elevation
- More common in women
Briefly outline Cardiac Syndrome X
- Angina of unknown cause (normal exercise test and angiography)
- More common in women
Identify four classes of angina
- Class 1: Angina with strenuous activity
- Class 2: Angina with normal activity
- Class 3: Angina with gentle activity
- Class 4: Angina at rest
Outline the pathophysiology of myocardial infarction
- Cessation of blood flow with exception of collateral flow
- Stagnant Blood
- Engorged vessels and bluish-brown hue due to de-oxygenation
- Fluid leak and oedema
- Death of cardiac muscle cells
How many millilitres of oxygen is required for each 100 grams of cardiac muscle?
- 1.3 ml
Identify four causes of death after MI
- Decreased cardiac output resulting in shock
- Damming of blood resulting in pulmonary oedema
- Sudden ventricular fibrillation
- Rupture of the infarcted area resulting in cardiac tamponade
What is a STEMI?
- Myocardial Infarction with ST elevation
- Occlusion involves entire thickness of the myocardium
What is an NSTEMI?
- Myocardial Infarction without ST elevation
- Occlusion involves subendocardial zone of myocardium
What is the difference between unstable angina and NSTEMI?
- In NSTEMI there is an occluding thrombus
- Resulting in myocardial necrosis
- And a rise in serum troponin or CK-MB
Identify the five types of myocardial infarction
- Type 1: Ischaemia due to primary coronary event such as a plaque erosion/rupture
- Type 2: Ischaemia due to increased oxygen demands such as coronary embolism, anaemia, hypertension
- Type 3: Sudden cardiac death
- Type 3: PCI
- Type 5: CABG
Identify signs and symptoms of a STEMI
- Chest pain that radiates to left arm, neck or jaw
- That does not respond to GTN
- Autonomic symptoms such as paleness and clamminess
- Thready pulse with hypotension, bradycardia or tachycardia
How would you identify an anterior wall MI using ECG?
- ST elevation in V1-V3
How would you identify an inferior wall MI using ECG?
- ST elevation in leads II, III and aVF
How would you identify a posterior wall MI using ECG?
- ST depression in V1-V3
- Dominant R wave
- ST elevation in V5-V6
How would you identify a lateral wall MI using ECG?
- ST elevation in leads I, aVL and V5-V6
How would you identify an anterolateral wall MI using ECG?
- ST elevation in leads I, aVL and V2-V6
- Inverted T waves in leads I, aVL and V3-V6
Identify the different types of troponin
- Troponin T: attaches complex to tropomyosin
- Troponin C: Binds calcium during excitation-contraction coupling
- Troponin I: Inhibits myosin binding site on actin
What limits the accuracy of CK-MB as a biochemical marker in MI?
What is its alternative use as a biochemical marker?
- Low levels of CK-MB in the serum of normal individuals and in patients with significant skeletal muscle damage,
- Reinfarction as levels drop back to normal after
36–72 hours.
What is the Killip classification used for?
- To assess patients with heart failure post MI
Describe the Killip Classification rankings
- 1: No crackles and no third heart sound
- 2: Crackles in <50% of the lung fields or a third heart sound
- 3: Crackles in >50% of the lung fields
- 4: Cardiogenic Shock
Identify three causes of mitral regurgitation following MI
- Left ventricular dysfunction and dilation
- MI of inferior wall causing dysfunction of papillary muscle
- MI of papillary muscles
What is the TIMI score?
- Used to determine likelihood of ischaemic events in patients with unstable angina or NSTEMI
- Risk factors include age, coronary artery disease, aspirin use, severe angina, ST deviation
What is the GRACE score
- Used to predict mortality risk in STEMI and NSTEMI
- Based on age, heart rate, systolic pressure, serum creatinine and Killip score
What is the role of aspirin
- Anti platelet
- NSAID
Explain how aspirin results in platelet actication
- Inhibition of COX-1
- Inhibited production of thromboxane A2 and platelet activating factor
Identify adverse effects of aspirin
- Gastrointestinal effects
- Postural encephalitis (Reye’s syndrome)
- Risk of bleeding if given with warfarin
What is the role of ticagrelor?
- Anti-platelet
Outline the mechanism of action of ticagrelor
- Blocks ADP receptors
- As ADP is used in activation of platelets
Identify two side effects of ticagrelor
- Dyspnoea
- Bleeding
Identify the mechanism of action of atorvastatin
- Inhibition of HMG-CoA reductase
- Reduced hepatic cholesterol synthesis
- Increased LDL receptor synthesis
Identify three adverse effects of atorvastatin
- Gastrointestinal disturbance
- Myalgia
- Raised concentrations of liver enzymes in the plasma
What is the active principle in Glyceryl Trinitrate?
- Nitric Oxide
Explain how GTN results in vasodilation
- Activation of Guanylyl Cyclase
- Conversion of GTP to cGMP
- Activation of protein Kinase G
- Phosphorylation of proteins
- Inhibition of Ca2+ induced smooth muscle contraction
Identify three effects of GTN
- Decreased afterload and preload
- Dilation of collateral vessel
- Antiatherosclerotic characteristics
How is GTN administered and why?
- Sublingual spray
- To avoid first-pass metabolism
Identify two side effects of GTN
- Headache
- Postural hypotension
What is referred pain?
- Pain felt in a part of the body that is remote from the tissue causing the pain
Where pain of acute myocardial ischaemia referred to?
- Skin areas supplied by intercostobrachial nerve (T2)
- Neck and jaw
- Epigastrium (T7,T8,T9 dermatomes)
Chest Pain:
How would this present in: Acute coronary syndrome?
- Central crushing chest pain
- Radiating to left arm / jaw
- Duration of more than 20 minutes
- Associated with sweating / clamminess / nausea / shortness of breath
- Symptoms are worsened by expiration and improved with GTN spray
Chest Pain:
How would this present in: Stable angina?
- Central chest pain
- Radiating to left arm / jaw
- Duration less than 20 minutes with full resolution
- Associated with shortness of breath
- Often triggered by exertion and resolved with GTN spray / rest
Chest Pain:
How would this present in: Pericarditis?
- Central chest pain
- Worsened by lying flat and improved leaning forwards
- Patient may have had multiple episodes in the past
Chest Pain:
How would this present in: Aortic dissection?
- Central chest / abdominal pain that is ‘tearing’ in nature
- Radiating through to the back
- May have associated syncope/ dizziness due to haemodynamic instability
Chest Pain:
How would this present in: Pneumonia
- Sharp chest pained worsened by inspiration
- Associated with cough, shortness of breath, fever, malaise
Chest Pain:
How would this present in: Spontaneous Pneumothorax
- Sudden onset of sharp chest pain that is pleuritic in nature
- Associated with shortness of breath
Chest Pain:
How would this present in: Pulmonary Embolism
- Sudden onset of chest pain associated with shortness of breath
Chest Pain:
How would this present in: GI Reflux
- Epigastric chest pain that is burning in nature and worsened by lying flat
Chest Pain:
How would this present in: Oesophageal Spasm
- Epigastric chest pain with no associated shortness of breath
- That is relieved by GTN spray, hence can be confused with ACS.
Which genes are affected in FH?
- LDL Receptor Gene
- Apo B100
How many people are estimated to be heterozygous for a mutation in the LDLR gene?
- 1 in 500
Identify the four main classes of mutations of the LDL receptor
- Reduced biosynthesis
- Reduces transport to cell surface
- Abnormal binding of LDL
- Abnormal internalisation of LDL
Identify two clinical features of FH
- Corneal arcus
- Xanthelasma (xanthoma when larger and nodular)
When is FH diagnosed?
- Total cholesterol level greater than 7.5 mmol/L
- Family history (cascade testing)
Outline the mechanism of action of ezetimibe?
- Reduces intestinal cholesterol absorption
- By inhibiting intestinal mucosal transporter NPC1L1
What are healthy total cholesterol levels?
- < 5 mmol/L
What are healthy LDL-C levels?
- < 3 mmol/L
What are healthy HDL-C levels?
- > 1 mmol/L
What should the ratio of total cholesterol to HDL be?
- 4.5
What is the role of psychology in coronary heart disease assessed in terms of?
- Beliefs about CHD
- Psychological impact of MI
- Predicting and changing risk factors
- Patient rehabilitation
How can the Health Belief Model be applied to CHD?
Susceptibility: Belief that they will not have a heart attack
Severity: Belief that lots of people recover from heart attack and thus heart attacks are not that severe.
Costs: Belief that interventions to reduce the risk of coronary heart disease, such as exercise, would require a lot of effort
What are predictors of non-attendance in cardiac rehabilitation programmes?
- Age
- Income
- Poor Health Beliefs
Stress management involves teaching individuals about what?
- Theories of stress
- Encouraging people to be aware of the factors that can trigger stress
- Teaching people to reduce stress, including ‘self-talk’, relaxation-techniques and general lifestyle approaches such as time management and problem solving.
- Stress management appears to reduce some of the risk factors for CHD, including raised blood pressure, blood cholesterol and type A behaviour.
- Stress management reduces angina, which in turn could reduce the occurrence of myocardial infarctions.
Outline Leventhal’s Self-Regulatory Model
- Illness is dealt with in the same way as any other problem
- Interpretation, coping and appraisal
- Until equilibrium is attained
What is Cardiac Rehabilitation?
- Sum of activities required to influence underlying cause of CHD
- To improve physical, mental and social conditions
- Using a multidisciplinary approach
Briefly outline the Evidence Base for Cardiac Rehabilitation
- Reduction in cardiovascular mortality (besides those with recurrent MI)
- Reduction in acute hospital admissions (including those with recurrent MI)
- Different models of CR delivery are equally effective
- Importance of early CR
