Cardiorespiratory 2 Flashcards
name the small ligament which attaches the aorta to the pulmonary artery
ligamentum arteriosum (aka Botallo’s ligament)
what does ectoderm (germ layer) give rise toy
ECTODERM= skin, CNS, PNS, eyes + internal ear
what does mesoderm (germ layer) give rise to
MESODERM= bones, connective tissue, skeletal muscle, urogenital system, cardiovascular system
what does endoderm (germ layer) give rise to
ENDODERM= lungs, gut + associated derived tissues e.g. pancreas, liver etc.
what type of mesoderm does the foetal heart develop from?
the foetal heart develops from CARDIOGENIC mesoderm (lateral plate)
at 35 days gestation what will the following give rise to:
1) truncus arteriosus
2) primitive atria
3) bulbus cordis
4) primitive ventricle
1) truncus arteriosus= proximal aorta + pulmonary artery
2) primitive atria= left + right atria
3) bulbus cordis= ventricular outflow tracts + right ventricle
4) primitive ventricle= left ventricle
what is dextrocardia (+when is it seen in clinic)
dextrocardia= heart is positioned to the right side of the chest instead of the normal left position
caused by mistake in ‘looping’ process during early foetal development
dextrocardia can be seen in situs invertus patients or can be ISOLATED dextrocardia
what is foramen ovale
foramen ovale is an opening/ shunt which allows blood to flow from the right atrium to the left atrium (during fetal development)
what is an atrial septal defect (ASD)
ASD= have a hole between the left and right atria
what is the function of foetal ductus venosus
ductus venosus= shunts blood from umbilical vein to IVC (bypassing liver)
what is the function of foetal ductus arteriosus
ductus arteriosus= shunts blood from pulmonary trunk to ascending aorta (bypassing lungs)
what is the treatment for a patent ductus arteriosus
administration of a prostaglandin inhibitor e.g. ibuprofen
what type of contrast is the gold standard for coronary angiogram
iodine contrast
which arteries supply the bundle branches of the heart?
the interventricular (descending) arteries supply the bundle branches
which coronary artery supplies the SA node?
right coronary artery (RCA) supplies SA node
RCA also USUALLY supplies the AV node (but circumflex can also supply AV)
define preload and explain in what pathologies does preload increase?
preload= volume of blood in the ventricles at the end of diastole
preload increases in patients with:
-hypervolemia (aka fluid overload)
-valve regurgitation
-heart failure
define afterload and explain when afterload increases
afterload= resistance ventricle must overcome to circulate blood
Afterload increases in patients with:
-hypertension
-vasoconstriction
-valve stenosis
-outflow stenosis
what is the difference between atherosclerosis and arteriosclerosis
atherosclerosis= a type of specific arteriosclerosis involving build up of fatty deposits (plaques) inside arteries
arteriosclerosis= general term for thickening and hardening of arterial wall (usually caused by atherosclerosis but not always)
what is the mechanism of atheroma formation?
n.b. atheroma= a fatty substance that builds up in your arteries over time
mechanism of atheroma formation:
1)endothelial damage
2) uptake of modified LDL particles, adhesion + infiltration of macrophages
3) smooth muscle proliferation + formation of a fibrous cap
= run risk of rupture + thrombosis/stenosis
name the main vasodilating and vasocontricting substances of the endothelium
endothelium releases various vasoactive factors to maintain vasomotor tone.
These can be vasodilatory factors such as nitric oxide (NO), prostaglandin 12 (PG12) and endothelium derived hyperpolarizing factor (EDHF) or vasoconstrictive factors such as thromboxane (TXA2) and endothelin-1 (ET-1).
why do patients with diabetes mellitus have accelerated rates of atherosclerosis?
GLYCATION: Glycation of LDL occurs chiefly due to the nonenzymatic reaction of glucose and its metabolites with the free amino groups of lysine in which LDL is rich.
this glycation is facilitated by the high glucose levels in diabetics. Glycated LDL is more likely to become oxidised and therefore become Ox-LDL and build up plaque
what is the difference between stable and unstable fibrotic caps?
stable fibrotic caps= slow growing, thick fibrin, unlikely to rupture, reduced blood flow, stable angina following exertion
unstable fibrotic caps= fast growing as rapid lipid deposition, thin + fragile fibrin cap, likely to rupture (with or withou haemorrhage, release of platelet tissue factor/ clotting cascade, collagen is exposed causing platelet aggregation =thrombus formation/ reduces lumen diameter
n.b. in unstable plaque thrombus formation it may occlude lumen completely = STEMI
or partially/ subocclusive= NSTEMI
Describe the mechanism of aspirin
- low dose inhibits COX-1, high dose inhibits COX-2
*COX-1 converts arachidonic acid into PGH2–> PGH2 is a precursor for other prostaglandins
*PGH2 converted to thromboxane A2 which is a potent stimulator of platelet aggregation!
so aspirin inhibits COX-1 which inhibits PGH2 which inhibits platelet aggregation == why its essential in PREVENTING CLOT IN MI
What type of drug is Clopidogrel/ Ticagrelor; describe their mechanism of action
Clopidogrel/ Ticagrelor are P2Y12 antagonists.
ADP is found in platelets + stimulates platelet aggregation (+ve feedback mechanism for platelet aggregation)
P2Y12 receptors are found on platelets; by inhibiting P2Y12 then we inhibit platelet aggregation and this prevents thrombus formation
Name and explain the mechanism of action of beta blockers
beta blockers e.g. propranolol, atenolol
- block beta adrenergic receptors (part of SNS)
- causes decrease HR, decrease contractility, decrease systemic vascular resistance (amount of force exerted on circulating blood by the vasculature of the body)
Name and explain the mechanism of action of ACE inhibitors
ACE inhibitors e.g. Ramipril, enalapril
*inhibit RAAS system; block ACE enzyme which converts angiotensin I–> angiotensin II= lower levels of angiotensin II= vasodilation= decreased BP= prevention of angiotensin II vasoconstriction
Name and explain the mechanism of action of calcium channel blockers
calcium channel blockers e.g. amlodipine, verapamil
- block voltage-gated calcium channels on cardiac muscle= less Ca2+ enters cell
- causes decrease in HR, increase in coronary vasodilation = decrease BP, decrease total peripheral resistance
Name and explain the mechanism of action of Statins
Statins e.g. atorvastatin
*competitive inhibitors of HMG-CoA reductase= reduces cholesterol synthesis (so LDL levels decrease)
statins increase the clearance of LDL from the blood
n.b. HMG-CoA reductase is the rate-limiting step in cholesterol synthesis
Define Systemic Vascular resistance (SVR) aka TPR
Systemic vascular resistance (SVR), also known as total peripheral resistance (TPR), is the amount of force exerted on circulating blood by the vasculature of the body. Three factors determine the force: the length of the blood vessels in the body, the diameter of the vessels, and the viscosity of the blood within them. Total peripheral resistance is an important concept to understand because it plays a vital role in the establishment and manipulation of blood pressure. This relationship is expressed mathematically as MAP = CO x TPR, where CO stands for cardiac output, and MAP stands for mean arterial pressure.
What is the role of nitric oxide in the CVD?
NO reduces infarct size and endothelial dysfunction
NO is an important determinant of basal vascular tone, prevents platelet activation, limits leukocyte adhesion to the endothelium, and regulates myocardial contractility.
mechanism:
NO activates guanylate cyclase to form cGMP
cGMP stimulates dephosphorylation of myosin light chain
causes vascular SMC relaxation= Vasodilation= v. effective on coronary arteries!
what is intermittent claudication
the thigh or calf pain pain with walking that comes with peripheral arterial disease.
PAD is when u have atherosclerotic plaques in peripheral arteries which reduces blood flow to extremities
what is the difference between stable and unstable angina
stable angina (more common) – attacks have a trigger (such as stress or exercise) and stop within a few minutes of resting.
unstable angina (more serious) – attacks are more unpredictable (they may not have a trigger) and can continue despite resting.
what are platelets produced by and under the influence of which hormone
platelets are produced by megakaryocytes in bone marrow under influence of thrombopoietin (hormone)
what is haemophelia?
Explain difference between haemophelia A and B
a rare disorder in which the blood doesn’t doesn’t have enough blood-clotting proteins
mutation on X chromosome
low level or complete absence of coagulation factor VIII or IX
Haemophilia A= deficiency of factor VIII
Haemophilia B= deficiency of factor IX (rarer)
symptoms of haemophilia:
-big lumpy bruises
-bleeding into muscle + joints particularly knees, elbow, ankles
-bleeding for long time after cut
- serious internal bleeding into vital organs after insult (deliberate or accidental)
what is von willebrands disease? Explain the 3 types.
vWD is an autosomal dominant disorder as a result of genetic mutation on chromosome 12
can be passed from either mother or father and therefore child has a 50% chance of being affected
carries and protects factor VIII when bleeding occurs
Type 1 vWD : 1% of population; reduction in von willebrand antigen + factor FVIII as a result
Type 2: von Willebrand factor doesn’t work properly + therefore have a low RiCof
Type 3: Extremely low levels or complete absence of Von Willebrand antigen, RiCof + factor VIII (most severe type)
symptoms; bruising, nose bleeds, heavy period, joint bleeds and muscle bleeds
define the following
* thrombosis
* embolism
thrombosis= pathological clot (thrombus) formation within a blood vessel
embolism= part of clot breaks off + travels through circulation until obstructed by vessels of smaller diameter
Patients with chronic inflammatory disease such as rheumatoid arthritis, IBD are more at risk of blood vessel wall pathology.
Explain with reference to the role of heparan sulfate and thrombomodulin why patients with chronic inflammatory conditions are more at risk of clot formation.
Heparan sulfate is on surface of endothelial cells, These heparin sulphate polysaccharides form projections into the lumen of a vessel. These projections prevent platelet adhesion to intact endothelial membrane= prevents clots.
Thrombomodulin binds thrombin which activates the natural anticoagulant, protein C, which reduces clotting.
Patients with chronic inflammatory disease have damage to endothelial wall, this reduces amounts of attached heparin + downregulates thrombomodulin= increasing risk of clot formation
what is the most common heritable risk factor for DVT/PE?
Factor V Leiden mutation= causes resistance to activated protein C
it is the most common heritable risk factor for DVT/PE (3-8% of ppl w european ancestry carry one copy of Factor V Leiden mutation)
What is a D-dimer test, how is it carried out and what does it indicate?
D-dimer is a fibrin degradation product (small protein fragment released into the blood when a thrombus is degraded by fibrinolysis.
BUT, can also increase w inflammation, pregnancy + cancer
D-dimer is a blood test that checks for blood-clotting problems; indicates blood clot/DVT/PE
*normal D-dimer effectively rules out DVT in those w low likelihood
*in those w high likelihood DVT a normal D-dimer is too low to use alone as diagnosis
what is the guideline for DVT (deep venous thrombosis) diagnosis
1) ultrasound of leg
+ve ultrasound= proceed with treatment
-ve ultrasound= D-dimer
2)D-dimer
+ve D-dimer= offer repeat scan in 6 days
-ve D-dimer= consider alternative Dx (diagnosis)
what is an INR blood test?
international normalised ratio (INR) blood test tells you how long it takes for your blood to clot. A test called the prothrombin time (PT) actually measures how quickly your blood clots. The PT results can be expressed as an INR to standardise the results.
define circulatory shock
circulatory shock= acute circulatory failure with inadequate or inappropriately distributed tissue perfusion resulting in cellular hypoxia + end-organ damage
define hypoperfusion
Hypoperfusion is a life-threatening condition characterised by poor circulation of blood from heart and lungs to the body’s organs.
How does the body regulate peripheral vasculature?
- vasodilation
*vasoconstriction
describe these mechanisms
vasodilation= enhances blood flow to certain areas and reduces SVR (systemic vascular resistance). Occures due to SMC relaxation. Activation of nitric oxide + prostacyclin via cGMP + cAMP. 2ndry messengers cause a decrease in calcium= SMC relaxation
vasoconstriction= controlled by SNS. Noradrenaline acts on alpha 1 + 2 receptors to cause vasoconstriction of vessels and SMC contraction. N.b. angiotensin + vasopressin have vasoconstrictive effects
Describe the 4 stages of circulatory shock
1) initial stage= switch from aerobic to anaerobic metabolism; increase lactic acid; subtle clinical signs
2)compensatory stage= SNS activated; increase catecholamine release, increase cardiac output; vasoconstriction, aldosterone release (urine decrease), heart rate + glucose levels INCREASE
3) progressive stage= body cannot maintain above stage.. decompensation begins,,, electrolyte imbalance, metabolic acidosis, respiratory acidosis, peripheral oedema, irregular tachyarrhytmias, hypotension, pallor, clammy skin, altered level of consciousness
4) refractory stage= irreversible cell damage, impending death
Explain the 4 classifications of circulatory shock
- OBSTRUCTIVE=physical obstruction to vessels entering/leaving the heart
*DISTRIBUTIVE=excessive vasodilation, excessive inflammation. Further classified into septic shock, anaphylactic shock, neurogenic shock
*CARDIOGENIC= failure of heart to pump blood
*HYPOVOLEMIC= due to reduced circulatory volume e.g. from external or internal bleeding, cholera, burns, haemorrhage, post-surgery
Obstructive shock can be caused by a tension pneumothorax. A life-threatening condition caused by continuous entrance + entrapment of air in pleural space= this compresses lungs, heart + blood vessels. Blood flow through the collapsed lung is severely obstructed this impair left ventricular filling by obstructing venous return to the heart (preload)
What are the signs and symptoms the patient wld experience in this scenario?
- tachycardia + tachypnoea
*hypoxia
*chest pain
*reduced breath sounds on affected side
- deviated trachea, AWAY FROM AFFECTED SIDE
Obstructive shock can be caused by a cardiac tamponade. A cardiac tamponade is the accumulation of pericardial fluid, blood, pus or air within pericardial space. Leads to increase in intra-pericardial pressure, restricting cardiac filling + decreasing cardiac output.
What are the signs and symptoms the patient wld experience in this scenario?
- tachycardia
-hypotension
-distant heart sounds
- elevated jugular venous pressure
What are the 3 stages of hypertension? Also mention the values for low BP, normal BP, Prehypertension:
systolic/diastolic
low BP= <80/<60
normal BP= 80-120/60-80
prehypertension=
120-139/80-89
stage 1 hypertension=
140-159/90-99
stage 2 hypertension=
160-180/100-120
stage 3 hypertension= 180+/120+
N.B. U DIAGNOSE BASED ON IF ONE OF THE NUMBERS IS HIGHER THAN NORMAL e.g. if patient has 120/99 then they have stage 1 hypertension as the diastolic reading is high
Describe the mechanism of angiotensin receptor blockers (ARBs)
ARBs bind to and inhibit the angiotensin II type 1 (AT1) receptor and are indicated to treat hypertension, congestive heart failure, and diabetic nephropathy.
what are natriuretic peptides (NPs) and what is the difference between ANP and BNP. What are their functions?
natriuretic peptides (NPs)= peptide hormones synthesised by cardiomyocytes
Atrial natriuretic peptide (ANP)= from atria
B-type natriuretic peptide (BNP)= from ventricles
functions of NPs=
* decrease renin release= decrease Ang II= decrease aldosterone
*increase GFR (by vasodilating afferent arterioles)
what is rheumatic heart disease
caused by rheumatic fever (RF), a systemic infection caused by untreated pharyngeal group A beta haemolytic streptococci infection
- rare disease due to penicillin treatment + decreased virulence of bacteria
*results in valve thickening and damage
carditis is one of RF presentation + can lead to rheumatic heart disease affecting mainly MITRAL valve (but also aortic a bit)
How does infective endocarditis present and what is its cause
IE/ Infective Endocarditis= is inflammation of endocardium caused by various organisms
its often seen in ppl with limited access to healthcare– those who didnt get antibiotic treatment for infection and it spread to hear
*usually present with FEVER and heart murmur +/- emboli/immune complex deposition
*other signs= splinter haemorrhages, conjunctival haemorrhage, osler nodes, janeway lesions
*causes valve damage + regurgitation due to bacterial vegetations
Define aortic stenosis + its causes.
What are the signs, symptoms + treatments?
Aortic stenosis (AS)= obstruction of blood flow during systole = when the aortic valve becomes narrowed, restricting blood flow from the left ventricle (LV) into the aorta during systole. This results in increased afterload and compensatory left ventricular hypertrophy (LVH).
causes:
- calcification + degeneration (aging)
- congenital: bicuspid valve
- rheumatic heart disease
symptoms:
-dyspnoea (increased diastolic pressure in stiff non-compliant LV)
-angina (increased o2 demand of hypertrophied LV)
-syncope (decreased blood flow to brain)
-LVF (contractile failure as ventricle dilates)
- sudden death (ventricular arrhythmias
signs:
-slow rising carotid pulse (pulsus parvus et tardus), heaving nondisplaced apex beat, LV heave+ aortic thrill
-S4 +/- ejection click
-ejection systolic murmur
treatment:
-surgical valve repair
-transcatheter aortic valve implantation (TAVI)
Define aortic regurgitation + its causes.
What are the signs, symptoms + treatments?
aortic regurgitation (AR)= occurs when aortic valve does not close completely during diastole, leading to the backflow of blood from the aorta into the left ventricle (LV).
AR results in a volume overload in the LV, causing compensatory dilation and, over time, hypertrophy. Chronic AR leads to progressive left ventricular dilation, reduced contractility, and eventually heart failure
Causes:
Valvular causes/aortic valve leaflet disease: congenital bicuspid aortic valve, rheumatic heart disease, calcific disease, infective endocarditis.
Aortic root causes/aortic root dilating disease: Aortic dissection, Marfan syndrome, Ankylosing spondylitis, syphilitic aortitis, or other conditions leading to aortic root dilation.
symptoms:
-often asymptomatic
-dyspnea (contractile failure as ventricle dilates)
-angina (increased o2 demand of dilated hypertrophied LV
signs:
-collapsing pulse
-displace hyperdynamic apex beat
-corrigan, quinkie,de musset, duroziez signs
-early diastolic murmur
-systolic murmur
- Austin Flint murmur in severe cases
treatment:
-aortic valve replacement
Define mitral stenosis + its causes.
What are the signs, symptoms + treatments?
mitral stenosis (MS)= stenotic mitral valve obstructs blood flow during diastole. LA is met with high resistance leading to enlargement
can lead to RVF as a passive consequence of increased left atrial pressure
causes:
-rheumatic fever
-congenital diseases
symptoms:
-dyspnoea, orthopnea (due to left atrial pressure, poor exercise tolerance)
-palpitations
signs=
-malar flush on face due to cardiac output
- purple lips
-pre-systolic murmur
-low volume pulse
Define mitral regurgitation + its causes.
What are the signs, symptoms + treatments?
mitral regurgitation (MR)= mitral valve does not close properly during systole, leading to backflow of blood from the left ventricle (LV) into the left atrium (LA).
causes:
1. mitral valve leaflet disease= mitral valve prolapse, rheumatic heart disease, infective endocarditis, connective tissue disease, calcified/stenotic mitral valve post surgery
2. subvalvar disease= chordal or papillary muscle rupture (post MI complication), papillary muscle dysfunction
3. functional MR in LV dilatation in DCM (dilated cardiomyopathy)
