CR2 Revision 2 Flashcards
What underlying pathologies might cause angina if the problem is occuring from a reduced o2 supply? [2]
Reduced O2 demand:
-
CAD:
- Atherosclerosis
- Post radiation therapy
- Spasm: normal coronary arteries which spasm causing temporary occlusion - Anaemia
What underlying pathologies might cause angina if the problem is occuring from an increased myocardial demand? [3]
- Left ventricular hypertrophy (from: HTN, aortic stenosis, aortic regurgiation, hypertrophic cardiomyopathy)
- Right ventricular hypertophy (from: pulmonary HTN, pulmnonary stenosis)
- Rapid tachycardiarythmias
Describe the pathway you would undertake to diagnose stable angina
Clinical assesment:
How many of the following do they have?
- General chest discomfort lasting 5/10 mins?
- Is this provoked by exercise?
- Is this relieved by rest or nitrates?
- Answer = <1, No diagnostic testing, no medication
- Answer = 2 characteristics = atypical angina
- Answer = 3 characteristics = typical angina
If Atypical angina or typical angina: initial management and investigations:
- CTCA
- Functional imaging if CTCA inconclusive
What key factors about chest pain would you ask someone with angina? [5]
Character
Location
Radiation
Duration
Provocation
Describe the managment pathway for someone with angina
How do different drugs / therapies target different physiological areas to relieve angina symptoms?
Increasing O2 delivery
Increase coronary blood flow:
- Nitrates
- CCBs
- Revasc.
- Nicorandil (Combination of K+ blocker and nitrate)
Reducing myocardial demand:
1. Reduce HR:
- BB
- ivabradine (funny current (If) inhibitor)
2. Decrease LV wall tension:
- BB
- Nitrates
- Nicorandil
- CCBs
- Ranolazine (Na+ pump inhibitor)
3. Reduce contractility:
- BB
- CCBs
4. Modify energy metabolism
- Trimetazidine
How can you pharmacologically reduce risk of MI for patients who are at risk of angina? [4]
- Aspirin: this produces an antithrombotic effect that helps to reduce the risk of heart attacks and strokes.
- Statins: reduces cholesterol (HMG Reductase inhibitor)
- Ace Inhibitor: If there is hypertension or diabetes or other comorbidities
-
P2Y12 receptor
antagonist: After PCI or if allergic to statins (P2Y12 receptor blockers are another group of antiplatelet drugs. This group of drugs includes: clopidogrel, ticlopidine, ticagrelor, prasugrel, and cangrelor)
What drug is initially used to treat stable angina? [1]
glyceryl trinitrate (GTN).
What are 3 risk factors for thromboembolism - what is the name for these factors combined? [4]
Virchow’s Triad
Endothelial injury
Stasis or turbulence of blood flow
Blood hypercoagulability
Inflammation: causes procaogulant state - acts in combination with one of the above
Why does blood stasis increase risk of clot? [2]
What are 4 risk factors that cause reduced blood flow / blood stasis? [4]
Why does blood stasis increase risk of clot? [2]
- less release of NO and prostacyclin from endothelium when blood is static
What are 4 risk factors that cause reduced blood flow / blood stasis? [4]
Immobilisation in bed following surgery or other conditions eg hip/pelvis fracture
Long-haul flights especially >8hours (prolonged sitting )
Obesity causing reduced exercise and decrease in venous return in deep leg veins
Sickle cell disease: red cell precipitation can occlude vessels
Why does vein wall pathology increase chance of DVT / PE?
How can vein wall pathology / damage occur? [3]
Heparan sulfate projects out of the endothelial wall. These projections prevent platelet adhesion to intact endothelial membrane. If damaged - less heparan sulfate:
- increases risk of clot formation, especially if combined with reduced blood flow
Vein wall pathology can occur from:
a) smoking / alchohol
b) diabetes
c) chronic inflam disease (RA)
How do you diagnose DVT?
Use Wells’ Score:
- Add up points on the score: 2 points or more is likely. 1 is unlikely
- If 2 or more score: have proximal leg vein ultrasound
i) have positive scan - give treatment
iI) have negative scan, repeat in 6-8 days - do a D Dimer test
a) if D-dimer is positive: repeat scan in 6-8 days
b) if second sacan D-dimer is negative - consider alternative disease, but discuss symptoms with patient so they can look out for it - Venography - gold standard
* o D-dimer is fibrin degradation product
o Is a marker of fibrin formation
o Raised in VTE and other pathologies
D dimer: fibrin degradation product released when thrombus is degraded by by fibrinolysis low D dimer = low DVT risk.
Why might someone have hypercoaguable blood? [3]
When would you consider hypercoagulable states for DVT?
Why might someone have hypercoaguable blood?
- Antithrombin deficiency
- Protein C or S defiency (anti-coagulant proteins)
- Factor V Leiden mutation :causes resistance to activated protein C
Consider when no obvious signs for VTE/ PE
Name 4 risk factors for thromboembolism
Pregnancy: enlarged fetus compresses veins (increases venous stasis), increased production of clotting factors to stop bleeding during birth
Prolonged immobilisation
Previous VTE Event:: Previous valve damage; Underlying cause for previous VTE and not may be left untreated treated underlying cause then may cause again
Contraceptive pill & HRT
Long haul travel
Cancer: can damage endothelium wall; increased risk from clotting factors
Heart failure : poor circulation of vascular system; more likely to be immobile
Obesity
Surgery: causing endothelial damage; causing immoblisation; causes increase in clotting factors
Severge burns endothlial damage
How would you investigate for PE?
Classification system? [1]
ECG? [3]
CXR? [1]
ABG [1]
o Wells Score greater than 4
ECG - sinus tachycardia, right heart strain. T-wave inversion on anterior leads (V1-V3). Classic finding: S (deep S wave in lead I), Q ( present in lead III) and T (inverted T in lead III).
o CXR- possible small pleural effusion, peripheral wedge shaped density above diaphragm, focal oligemia. Most common finding with PE patients is a normal CXR, but used to excludes other diagnoses
o ABG - often hypoxic, low CO2 (due to hyperventilation)
What Wells score would indicate PE? [1]
greater than 4
What type of imaging would be best for diagnosis of PE?
CT pulmonary angiogram
Explain how PE can cause cardiac failure xx
- Right ventricle has thin muscle (pulmonary vasculature is a low pressure system)
- Increased pressure in the pulmonary vasculature due to PE
- Thin right ventricle has to work harder / dilates and is understrain
- Dilatation of right ventricle gets in the way of the left ventricle (pushes through interventricular septum) – less filling of the LV: fall in BP / decreased CO
- This causes release of adrenaline / noradrenaline: causes PE to vasoconstrict.
- Repeats cycle – can lead to MI / arrthymia
- So main cause of death is right sided heart failure leading to left sided heart failure cardiac arrest
- ALSO get patent foramen ovale in 1/3 patients: severe hypoxaemia & increased risk of stroke
-
Name & briefly explain 3 clinical outcomes of PE [3]
- Cardiac failure (see next slide)
- Respiratory failure: due to V/Q mistmatch (part of lung not perfused bc blocked by thrombus); low right ventricle output; patent foramen ovale
- Pulmonary infarction
Explain mechanism of how heparin works to treat PE [3]
Name a drug that is a synthetic heparin [1]
Heparin binds to antithrombin and activates it; activated complex then inactivates factor Xa, preventing conversion of prothrombin to thrombin (thrombin converts fibrinogen into fibrin - integral step in clot formation)
Fondaprinux
Why is heparin treatment potentially dangerous? [2]
Can cause bleeding in brain; retroperitoneal; site of fall [1]
Causes thrombocytopenia: platelet count drops, but increased risk of thrombus [1]
Which artery is occluded here? Explain what type of ACS is causing this ECG [1]
a) LAD
b) RCA
c) LCA
d) circumflex artery
Which artery is occluded here? Explain what type of ACS is causing this ECG [1]
a) LAD
b) RCA
c) LCA
d) circumflex artery: ST depression in V5 & V6
What is the difference in the pathology of STEMI vs non STEMI?
Pathophysiology of acute MI:
· NSTEMI
o Ruptured coronary plaque with sub-occlusive thrombus - impacted flow of oxygen to myocytes & therefore myocyte necrosis
o Plaques rupture when they are unstable and there is friction from passing blood (statins can stabilise the plaque)
o Thrombus forms but occludes part of the lumen
o NON-diagnostic ECG
· STEMI
o Ruptured coronary plaque with occlusive thrombus - impacted flow of oxygen to myocytes & therefore myocyte necrosis
o Thrombus forms occluding the whole lumen
o DIAGNOSTIC ECG
Diagnosis of MI need which criteria? [3]
ALL OF:
- Acute MI - troponin must be elevated
- Rise and/or fall of troponin with at least one value >99th percentile of the Upper Range of Normality (URL)
3. Clinical evidence of acute MI
- Symptoms of acute MI
- ECG changes (Q wave)
- ID of coronary thrombus by angiography
- Imaging from MRI / Echo
What does this ECG indicate? [2]
T wave depression in V1-V3
Occlusion in LAD
Explain the basic overview from vessel injury –> stable haemostatitc plug
- Vasoconstriction occurs to reduce blood loss
- Collagen released is also. This causes platelet released, which in turn causes release of serotonin, TXA ADP & platelet phospholipids.
- Serotonin then helps with vasoconstriction, whilst TXAADP helps with platelet aggregation.
- Together they help to make a primary plug
- Through vasoconstriction, shear stress is increased. This cause various molecules to be release, including VWF (important in platelets adhering to vessel walls)
- Simultaneously to vasoconstriction: tissues factor is exposed. This causes coagulation cascade.
- Platelet Phospholipid is the surface for many of the coagulation cascade that occurs.
- Thrombin is created fibrin
- together makes stable hameostatic plug
Give brief overview on how primary haemostasis occurs to make platelet plug
- Vessel injury causes collagen to be exposed
- VWF binds to collagen one side, and the otherside to platelets via glycoprotein 1b receptor
- Platelets become activated, start clump other platelets. Through glycoprotein IIb, IIIa and fibrin, form stable haemostatic plug.
Fill in the differences
Describe how the kidney reabsorbs bicarbonate under normal physiological conditions
At PCT of Kidney, body reabsorbs most HCO3-.
- HCO3- filtered through glomerulus.
- Activity of carbonic anhydrase inside AND outside cell is increased.
- Increased intracellular CA activity increases excretion of H+ outside of the cell through the Na/H+ ATPase pump.
- Extracelluar H+ then reacts with HCO3-, via carbonic anhydrase, to make Co2 and H20
- Co2 reabsorbed into cell. CO2 reacts with H20 via CA to make more H+. repeat
- HCO3- absorbed into blood
Describe how the kidney reabsorbs bicarbonate if there is respiratory alkalosis
- Decreased carbonic anhydrase activity within the cell: less CO2 converted to bicarbonate and protons. Less protons in cell means less protons excreted by sodium-proton exchange ATPase in luminal wall into urine to be excreted.
- This results in less bicarbonate is converted to CO2 in tubule and filtered bicarbonate is excreted in urine
- Leads to decreased excretion protons and decreased bicarbonate reabsorption
Explain the MoA behind HACE
In hypoxaemia ATP supply in nerve cells decreases and sodium pumps run down
Sodium leaks into nerve cellpulling water with it brain cells swell.
Raises intracranial pressure (icp) and blocks cerebral veins
Cerebral circulation fails, hypoxia worsens, neurons, starved of oxygen and squashed together, start to die.
Dead neurons release ions and fluids – worsen cerebral oedema
Explain the mechansim of action of an ADP receptor antagonist [2]
Name three of the most common [3]
The ADP receptor antagonists bind to the P2Y12 receptor to prevent ADP-induced platelet activation
Clopidogrel
Prasugrel
Ticagrelor
