CR Cardio-related issues Flashcards
Atrial Fibrillation ECG diagnosis
absence P waves
Concentric and Eccentric hypertrophy
o Concentric
Due to increased afterload = aortic stenosis
• Afterload = the stress in the wall of the left ventricle during ejection
Wall thickness increases, compliance reduced (stiffness)
o Eccentric
Volume overload that leads to dilation of chamber (e.g. Regurg.)
Elevates oxygen demand, lowers efficacy
concentric can lead to eccentric (reduced compliance = volume overload)
Rheumatic Heart Disease
Mainly affects the aortic and mitral valves
Underlying mechanism is believed to be production of antibodies against person’s own tissues after strep A infection
Valves become thickened (fibrosis) = become narrow and incompetent.
Aortic Stenosis Summary
Causes: Age, Congenital Bicuspid valve (CBV)
Symptoms: LV failure, breathlessness (pleural effusion due to increased LAP), angina (more O2 demand), Syncope (flow can’t readily increase)
Signs: SLOW RISING CAROTID PULSE, S4 heart sound (forceful contraction of atria that cannot contract any further), severe pressure gradient LVP>LAP
Treatment: TAVI surgery
Aortic Regurg Summary
Causes:
Aortic Valve Leaflet Disease
Aortic Root Dilating Disease
Symptoms: Dyspnoea (pleural effusion due to increased LAP), angina (more O2 demand), eccentric hypertrophy
Signs: RAPIDLY RISING CAROTID PULSE, end-diastolic murmur (aortic backflow), ejection murmur (turbulent ejection from overloaded LV)
Treatment: Surgery
Mitral Prolapse summary
Cause:
Marfan syndrome, Ehler’s danlos (connective tissue disorders)
Myxomatous degeneration (pathological weakening of chordae tendinae)
Symptoms: asymptomatic NOTE: during systole valve prolapses back into LA = MR
Signs: Mid-systolic click (MR), late murmur (regurg.)
No treatment necessary
Mitral Stenosis Summary
Causes: Rheumatic fever
Symptoms: Increased LAP, Atrial fib. (loss of conduction tissue
Mitral Regurg. Summary
MOST COMMON
Causes:
Mitral Valve Leaflet D
Subvalvular Disease
Functional MR (LV dilation)
Symptoms: Increased LAP, Atrial fib. (loss of conduction tissue
Causes of Aortic Valve Leaflet Disease
Calcific disease, CBV, rheumatic, infective endocarditis
Causes of Aortic Root Dilating Disease
Marfan syndrome, aortic dissection, ankylosing spondylitis
Causes of Subvalvular Disease in mitral regurg.
Chordal rupture, Papillary muscle dysfunction or muscle rupture
Hypertension grades
Grade 1 = Ambulatory blood pressure monitoring (ABPM) = 135/85
Grade 2 = ABPM is = 150/95
Treatment for Isolated Systolic Hypertension
Lower sodium and richer fruit and vegetable diet
ISH serious in elderly
Postural Hypertension Clinical Definition
A decrease in standing > 20 mmHg or DBP >10 mmHg when associated with dizziness/fainting
Why does • Systolic pressure generally increase with age
o Elastin gradually replaced by collagen because of free radical damage
Classes of Hypertension
Primary = 90-95% of cases. (idiopathic)
Secondary = about 5% - clear underlying cause
Renal/renovascular disease
Cushing’s syndrome (adrenal cortical tumour)
Conn’s syndrome (hypersecretion of aldosterone)
Coarctation of the aorta.
Iatrogenic.
o Hormonal and oral contraceptive.
o NSAIDs
Thyroid (either hyper/hypo) or parathyroid disease
Blood Pressure is Controlled by
- Baroreceptors in carotid artery (neuronal system).
2. The renin-angiotensin-aldosterone system (RAAS).
Hyponatremia symptoms
Is serious as it affects action potential production and can cause brain swelling.
Mild: Loss of energy, fatigue, Confusion, muscle weakness
Severe: Nausea, vomiting, headache, seizures coma.
Obesity and Hypertension
•Obesity = increases renal renin release, angiotensin formation and sodium retention.
High levels of leptin (due to increased number of fat cells) increase sympathetic vasoconstriction
Hypokalaemia = increases plasma renin, angiotensin II
Exercise and lose weight (best therapy)
Approach to Hypertensive Treatment
Step 1:
People under 55 should receive and ACE-blocker (Ramipril) OR a ARB (Losartan) (angiotensin II receptor blocker)
• Do not combine ACE inhibitor and ARB
People over 55 = calcium channel blockers (Consider for Afro-Caribbean’s)
• If not suitable = thiazide-like diuretic (decrease intra-vascular volume).
If diuretic treatment = offer thiazide-like diuretic such as:
• Chlortalidone or indapamide
Step 2:
• CCB + ACE inhibitor or an ARB
• If CCB not suitable = thiazide-like diuretic + ACE/ARB
• For black people = consider ARB > ACE + CCB.
Step 3: Treatment with three drugs if required.
Step 4: If no change (resistant hypertension) consider adding a fourth antihypertensive drug.
Metabolic syndrome triad
obesity, hypertension, diabetes
Most common type of cardiac defect
Ventricular Septal Defect (Acyanotic)
Stages of Atherosclerosis Development
1) Endothelial damage that makes vessel dysfunctional and alters permeability
2) Uptake of modified LDL particles, adhesion and infiltration of monocytes that become macrophages —> foam cells
3) As a response to injury, smooth muscle proliferates and moves into intima to form fibrous cap
Vasodilators
NO
PGI2 (Prostaglandin I2/prostacyclin)
LDL uptake in Atherosclerosis
LDL receptor normally recognises apolipoprotein B100
Modified LDL is not recognised by receptor (AB100) and are taken up by macrophages
No negative feedback = uptake is unlimited causing accumulation.
What causes proliferation of smooth muscle into intima in atherosclerosis
Platelet derived Growth factor released from macrophages
Atherosclerosis treatment
Statins -HMG CoA inhibitor (reduces intracellular cholesterol synthesis)
- Increase in LDL liver receptors
- Reduced plasma cholesterol
Polypill - contains a statin, 3 b.p. lowering drugs, folic acid and aspirin
(2012 onwards without aspirin)
Causes of Angina
DECREASED myocardial O2 supply:
- Coronary artery disease
- Severe Anaemia
INCREASED myocardial O2 demand:
- Left ventricular hypertrophy
- Right ventricular hypertrophy
- Rapid tachyarrhythmia.
Angina ECG features
Diagnostic Features:
Planar or down-sloping ST depression
Prognostic features:
- Poor exercise tolerance
- Early ST depression
- Slight ST depression (ischaemia), poor exercise tolerance
Angina treatment
Increase O2 delivery (coronary flow):
- Nitrates
- CaBs
- Nicorandil
- Revascularise
Reduce O2 demand:
Reduce heart rate:
- BB
- Ivabradine
Reduce LV wall tension:
- BB
- Nitrates
- Nicorandil
- CaBs
- Ranolazine
Reduce contractility:
- BB
- CaBs
Angina Second degree prevention
Aspirin to all patients
Statins to all patients
ACE-I if any other indications (HT/DM)
Total body iron
3-5g
2g in circulating Hb
Absorption of iron
Duodenum
Role of Transferrin
Takes up fe2+ (can carry 2)
Clinical measurement for suspected iron deficiency
Role of ferritin
stores iron, releases when needed (buffer against iron deficiency and overload)
small amounts in serum = iron carrier
What can serum ferritin be used for
Diagnostic test for iron deficiency anaemia.
Definition of Anaemia (measurements)
<13.5 g/dl (male)
<11.5 g/dl (female)
Anaemia signs and symptoms
Symptoms: Tiredness Fainting Shortness of Breath Worsening Angina Palpitations
Signs: Pallor (unhealthy pale appearance) Rapid heart rate Bounding pulse Systolic flow murmur Cardiac failure Retinal haemorrhages
What is classed as Iron Deficiency
10ml loss/day
Types of microcytic anaemia
Iron Deficiency Anaemia
Thalassaemia (alpha and beta)
4 missing genes = alpha
2 missing genes = beta
Types of normocytic anaemia
Chronic Disease
Haemolytic Anaemia:
Abnormal breakdown in spleen/liver
- Hereditary spherocytosis (Autosomal dominant)
- Sickle cell disease
- Thalassaemia (microcytic)
- Anti-body induced
- Rhesus mismatched transfusion
Abnormal breakdown in blood:
- ABO mismatched transfusion
- Snake bites
- Infections
- Malaria
Types of macrocytic anaemia
Vitamin B12 (Cobalamin) Deficiency
- Pernicious Anaemia (autoimmune again parietal cells)
- Surgical gastroectomy
- Chron’s disease
Folate (Vitamin B9) Deficiency
Vitamin B12 absorption
Absorbed in ileum after binding to intrinsic factor (from parietal cells in gastric musoca)
Diagnosis of Vitamin B12 Deficiency
increased serum methylmalonic acid
Symptoms of Vitamin B12 Deficiency
Insidious = stores of B12 can be almost 3 years, so symptoms are gradual but could be fatal.
Anaemia
Glossitis = inflammation of the tongue
Mild Jaundice = due to RBCS breakdown
Neurological Symptoms
Virchow’s Triad
Reduced blood flow (stasis)
Vessel wall disorder.
Hypercoagulability
Deep vein thrombosis Diagnosis
Dependant on Wells Score
If above 2 = compression ultrasound
If below/CUS is negative = D-dimer
Pulmonary embolism Diagnosis
ECG = sinus tachycardia, T wave inversion on anterior leads (V3, V4)
Arterial blood gases = hypoxia, low CO2
CXR = small pleural effusion, peripheral wedge shaped density above diaphragm
Treatment of VTE, DVT, PE
Start heparin if likely diagnosis
Continue if diagnosed
Stop heparin after min. 5 days
Continue Warfarin
Direct acting oral anti-coagulants (DOAC)
Dabigatran = acts on thrombin Rivaroxaban = acts on Factor Xa Apixaban = acts on Factor Xa Edoxoban = acts on Factor Xa
Low Molecular Weight Heparin (LMWH)
Anti-Xa and Anti-thrombin
Safer than unfractioned heparin
Half-life about 4 hours
Side Effects:
Osteoporosis
Major bleeding
Heparin induced thrombocytopenia.
Why is Unfractioned Heparin used over LMWH
when rapid reversibility is required
Fondaparinux
Synthetic pentasaccharide
Warfarin
Vitamin K antagonist (factors II, VII, IX, X, protein C&S)
Delayed onset of action
Side Effects:
major bleeding risk
TERATOGENETIC
Aspirin
Irreversibly inhibits COX (mainly COX1) and thromboxane synthase (potent platelet stimulator)
Contraindications:
Children <16 (fulminant liver failure)
Caution in patients with existing bleeding disorder and Patients with hypertension
Given in all cases of suspected STEMI
Side Effects:
Commonly overdosed causes:
Respiratory alkalosis
Severe metabolic acidosis
Can initiate asthma, cause bleeding, Gastritis, tinnitus, renal impairment.
Beta Blockers
Stop the effects of the sympathetic nerve stimulation or circulating catecholamines the beta-adrenoceptors
Beta 1 = mainly in the heart, also kidney.
o Heart: In the SA node reduces H.R, in myocardium decreased cardiac contractility.
o Kidney = inhibits release of renin, reduces activity of RAAS system.
Beta 2 = lung, peripheral blood vessels, skeletal muscle,
o NS = inhibits release of neurotransmitters, decreases SNS
Contraindications:
Pregnancy (IUGR, neonatal hypoglycaemia, bradycardia)
Breast Feeding
Side Effects: Bronchospasm Bradycardia Hypotension Erectile Dysfunction
Example: Propanolol
Statins
Inhibits action of HMG-coA reductase, by preventing conversion of HMG-CoA to mevalonic acid, increases LDL receptors expressed outside cell
Non-cholesterol effects:
o Decreased Inflammation
o Increased Apoptosis.
o Gene Regulation
Side Effects: Increases likelihood of developing diabetes. Sleep disturbance (Rare) hepatitis and jaundice. Muscle toxicity
ACE inhibitors
Inhibits plasma ACE competitively, leads to vasodilation.
Side Effects:
Dry irritant cough (accumulation of bradykinin)
Angioedema, impairment of renal function
Examples:
Captopril
Ramipril
Clopidogrel
P2Y12a inhibitor, Further inhibits platelet aggregation
Acute Myocardial Infarction Symptoms
- Chest Pain
- S4 (atrial contraction during diastole = ejection of blood into ventricles that cannot expand any further).
- Low grade fever
Autonomic disturbance (stimulated by low CO).
- Tachycardia
- Sweating
- Vomiting
STEMI Reperfusion Therapy
- Aspirin and ticagrelor (platelet aggregation inhibitor)
- Heparin (anticoagulant)
- PPCI (primary percutaneous coronary intervention = coronary angioplasty)
NSTEMI Emergency Treatment
- Aspirin and ticagrelor
a. P2Y12 - GPIIb/IIIA inhibitor.
- Fondaparinux (factor Xa inhibitor)
- Anti-ischaemic drugs (BB, nitrates)
- Angiography (PCI if required)
Secondary Prevention of Myocardial Infarction
Lifestyle
Drugs = aspirin, ticagrelor, statins, beta blockers, ACE-I
Devices = implantable cardioverter defibrillator (ICD)
- secondary VF (>24 hours after onset of infarct) or LV ejection fraction is <35%
Types of Stroke
ISCHAEMIC (blood clot in cerebral artery ) - 85% of all strokes
HAEMORRHAGIC (Intracerebral haemorrhage)
LACUNAR (Occlusion of deep brain structure) - no cortical signs
Location of Stroke
Branches of MCA - highly tortuous (turbulent flow)
Branches form lenticulo-striate arteries - Leave MCA at nearly 90 degrees
Tonsillar Herniation
rise in ICP can cause cerebellum to extrude through foramen magnum - • Compression of lower brainstem and upper cervical cord.
How is K+ removed in the brain
K+ released into extracellular space and removed by glial cells (buffer electrolyte changes).
Excess Glutamate
NMDA and AMPA receptors
Excess stim. –> excess influx of Ca2+ ions into nerve cells
Excess Ca2+ = increase metabolic demand = uses more oxygen –> Hypoxic = absence of O2 = free radicals
Leads to apoptosis/cell death
Penumbra region
Hypoxic neurons near hypoxic brain region which can survive
Penumbra region Treatment
1) Restore Blood Flow:
Tissue plasma activators.
o Statins improve cerebral blood flow
Increase NO production.
- Combat Excitoxicity = NMDA antagonists, AMP antagonists
- Combat Free Radical Damage = antioxidants, free radical scavenger enzymes (superoxide dismutase), cool down the brain
Shock criteria
Likely if Mean Arterial Pressure is <60 mm Hg Other clinical signs of hypo perfusion: Tachycardia Tachypnoea Mental confusion.
What mediates Constriction of arterioles
Mediated by sympNS
• Noradrenaline (alpha receptors on arterioles)
• Angiotensin 2 (hormonal control)
Mediated by local control:
• Endothelin: released from lining epithelium (can constrict/dilate)
• Nitric Oxide: vasodilator
• Prostacyclin: vasodilator produced by endothelial cells.
Prostacyclin
from prostaglandins (arachidonic acid):
o Inhibits platelet activation
o Reduces calcium entry into smooth muscle cells.
o Opposite to thromboxane.
Stages of Shock
Compensation:
Baroreceptors detect fall in BP = increase heart rate –> increased CO to restore BP
Decompensation:
arterioles cannot maintain constriction; blood preload reduction is too great.
Organs are not perfused and start to fail.
Classes of Shock
Obstructive Shock: Physical obstruction to the vessels entering or leaving the heart
o Pulmonary embolism.
o (Tension) Pneumothorax.
o Cardiac tamponade.
Distributive Shock: Loss of vasoconstriction in one or more end organs
Classical Symptoms:
o Fever (may be absent in elderly/immunosuppressed).
o Chills
o Fatigue
o Vomiting
Cardiogenic Shock: Due to failure of heart to pump effectively Symptoms of acute cardiac ischemia: Chest pain Shortness of breath Nausea Vomiting
Hypovolemic Shock: Normally due to haemorrhage
Classical Signs (note = history is vital).
o Low blood pressure
o High heart rate
o Confusion/anxiety
o Slow capillary refill
How much blood loss is life-threatening
Acute loss of 40% (>2 litres)
Classes of Hypovolemic Shock
Class 1 = loss of <15%. Fully compensated (patient = tired)
Class 2 = loss of 15-30%. Tachycardia, tachypnoea, decrease in pulse pressure, delayed cap refill etc…
• Rest + normal access to water/food = fully compensated.
Class 3 = loss of <30%. Most patients’ = blood transfusion or plasma volume expanders. May have end-organ damage.
Class 4 = loss of > 40%. May be unconscious. This is life threatening. Blood transfusion should be given immediately
Septic Shock Management
Hypovolemia = restore blood volume with i.v. colloids and crystalloids
Vasopressor drugs (dopamine, noradrenaline, ADH).
How many genes code for alpha and beta globin
Alpha = 4 genes (chromosome 16)
Beta = 5 genes (chromosome 11)
Two different forms of Fetal Haemoglobin
Hb Gower-1 = produced in the embryonic yolk sac
o First 6 weeks
o Zeta 2 Epsilon 2
o Variants may occur in early weeks
Fetal Haemoglobin F = zeta gene switched off after 6 weeks.
o Made in liver and spleen
Lower affinity for O2 than Hb Gower-1 but still higher than maternal Hb.
o Alpha 2 Gamma 2
Alpha Thalassemia and types
Deleted/faulty alpha gene on chromosome 16
One Alpha Gene Defective = Alpha thalassemia minima
- No clinical symptoms
Two Alpha Genes Defective = Alpha thalassemia minor
o Mild microcytic anaemia
o Often mistaken as IDA
Three Alpha Genes Defective = Haemoglobin H disease
o Two unstable haemoglobins present: Haemoglobin Barts (gamma 4) Haemoglobin H (beta 4)
o Have higher oxygen affinity = poor release of O2 in tissues
Four Alpha Genes Defective:
• Fetus cannot live outside the uterus
• Hydrops fetalis = fluid accumulation
Beta Thalassemia
Autosomal recessive, Point mutation on chromosome 11
Beta thalassaemia minor (β+) one allele defect
Beta thalassaemia major (βo) both allele defect.
Pathological Effects
• Excess alpha globin produced. These can transfer O2 but are unstable, precipitate on RBC membrane.
o Intra-medullary (in bone marrow) destruction of developing RBCs
o Erythroid hyperplasia.
o Ineffective erythropoiesis.
• Results in severe hypochromic microcytic anaemia
Excess haemolysis
Free iron may be released into the blood:
- Fenton reaction = iron + hydrogen peroxide (from mitochondria) = hydroxyl radicals.
- Radicals damage all biological tissues –> diabetes, glandular dysfunction, cirrhosis
Excess haemolysis Treatment
Desferoxamine • Toxicity with higher doses Deferiprone • Oral • Neutropenia • Danger in pregnancy. Deferasirox • Oral • Gi bleeding
SICKLE CELL DISEASE Genetics
Mutation: glutamic acid to valine
o Codon 6 of beta globin chain.
o Produces βS chain.
Haemoglobin S produced (α2βS2)
Deoxygenated blood = haemoglobin S may precipitate or crystallize.
o RBCs have decreases survival time –> anaemia.
o Occlude capillaries –> lead to ischemia and infarction
Haemoglobin C
Haemoglobin E
Haemoglobin C - abnormal beta subunit Reduced plasticity/flexibility of RBCs. Excess red cell destruction: Heterozygous = no anaemia. Homozygous = mild haemolytic anaemia
Haemoglobin E - single point mutation in beta subunit
Inherited from both parents.
Mild beta thalassemia a few months after birth.
Signs and Symptoms of Heart Failure
Symptoms:
Fatigue
Dyspnoea
Oedema
Signs: Cool Skin (blood is redistributed to more vital organs) Peripheral cyanosis Basal crackles Increased JVP Ankle swelling Ascites = fluid in abdominal cavity Tachycardia Sweating S3 = rapid filling in diastole. Alternating pulse
Chest-X Ray of Heart Failure
A. Alveolar oedema B. Kerley B-lines. C. Cardiomegaly. D. Blood flow perfusion to upper lobes. E. Effusion
Complications of Heart Failure
Intravascular thrombosis due to stasis = pulmonary and systemic embolisms
Infection = chest infection (because of oedema) or ulcerated cellulitic legs
Valvular dysfunction = enlargement of LV or RV.
Multi-organ failure = liver or renal failure
Cardiac arrhythmias.
Brain Natriuretic Peptide (BNP)
Secreted by myocardial cells in response to increased LAP
- Promotes natriuesis (excretion of sodium and therefore water) and vasodilation
- Inhibits ADH and aldosterone release
Levels >100 pg/ml = heart disease as likely cause of dyspnoea and fluid retention
Diastolic failure
ventricle is not able to fill properly = concentric hypertrophy
Systolic failure
heart cannot contract properly = eccentric hypertrophy
Systolic Failure Medication
ACE Inhibitors
ARBs (if ACE’s not tolerated)
Beta-Blockers (all grades of failure)
Spironolactone (potassium sparing drug)
