Cardiovascular Flashcards
blood clot/ haemotoma
Solidification of blood constituents outside the vascular system or after death
virchow’s triad
endothelial injury, abnormal blood flow, hypercoagulability
hypercoagulability-
Alteration of the blood coagulation mechanism}} (esp. platelets and clotting cascade) that in some way predisposes to thrombosis
- May be genetic disposition eg. protein S or C deficiency
- May be acquired eg. :after surgical procedures
at what point does the primordial heart and vascular system begin to develop?
3rd week of gestation
trilaminar discs form
skeletal muscles, blood cells, most of CV system
heart fields are
cells that go on to from the cardiovascular system
formation of primary heart tube
folding of the embryo in the midline (from cranial to caudal) which brings the heart fields together. Endocardial tubes then fold into the midline and fuse to form one, primary heart tube.
Layers of primary heart tube
- Myocardium: walls of the heart, formed from mesoderm containing myocardial progenitors
- Cardiac jelly- separates the myocardium from the cardiac tube
- Endocardium- inner lining of the heart
cardiac looping
the cardiac tube elongates, and cardiac looping occurs forming 2 bulges: the bulbus cordis and primordial ventricle.
most caudal of primitive heart chambers?
sinus venosus
What sources does the blood flow to the sinus venosus of the primitive heart come from
- Vitelline veins- returning poorly oxygenates blood from the yolk sac
- Umbilical veins- carrying oxygenated blood from the chorionic sac
- Common cardinal veins- returns poorly oxygenated blood from embryo itself to the heart
what happens when heart tub elongates and loops:
- The primitive atria are displaced dorsally and cranially
- The primitive ventricles are displaced caudally with the left ventricle to the left and the right ventricle towards the right
cardiac septation
myocardium divides and thickens to form dorsal and ventral endocardial cushions which develop into the septa which divides the atria from the ventricles. The interventricular septum grows upwards to separate right and left ventricles joining to the endocardial cushions at around week 8. The mitral valve and tricuspid valve begin to form after septation.
Septum primum forms and grows downwards
foramen primum space formed
Foramen secundum forms in septum primum
septum secundum begins to form
which valves begin to form after septation?
mitral valve and tricuspid valve
fetal blood circulation
Fetal lungs are not yet functional so oxygen rich blood from chorionic sac/placenta enters RA and goes directly into the LA.
foramen ovale
hole in the atrial septa that permits oxygen rich blood to move from RA to LA
- Patent ductus arteriosus-
connection between pulmonary artery and aorta in the fetus remains open after birth
patent foramen ovale –
due to abnormal resorption of septum primum during formation of foramen secundum and can result in short septum primum and therefore foramen ovale
- Transposition of the great arteries
- pulmonary artery and aorta are swapped
- Truncus arteriosus-
pulmonary artery and aorta don’t develop
positioning of heart
sits in the midline of the thoracic cavity and the apex of the heart projects left
diastole
passive filling of chambers
systole
contraction of chambers
features of arteries near heart and in body
Muscular- mostly in the rest of body
Elastic- close to heart
Blood vessels decrease in size moving away from the heart and then increase on return to the heart.
capillaries
site of diffusion
The arterial system is:
- Relatively low volume, high pressure
- Low capacity
- Low compliance walls- resist deformation so doesn’t expand or shrink
the venous system is:
- High volume, low pressure
- High capacity
- Walls have increased compliance so stretchy
Capillary beds:
- Site of exchange within interstitial fluid/ tissues
- Delivers nutrients and collects waste
- Feeds into venous system, returns to heart
metarteriole
network of tiny true capillaries branch from capillary bed
epithelial layer- tunica intima
- Lines inside of the entire vascular system
- Flattened epithelial cells
- Supported by connective tissue, basement membrane and collagen
Muscular Layer- Tunica media
- Smooth muscle
- Thickness highly variable depending on vessel types
- Absent in blood capillaries
supporting layer- tunica adventitia
- Connective tissues- elastin and collagen
- Carries small blood vessels which supply vessel walls
layer that indicates what vessel it is
Muscular Layer- Tunica media, arteries are more well defined
pulmonary circulation
Blood exits the right ventricle via pulmonary trunk → divides into L + R pulmonary artery → smaller branches pass into the lungs → blood accumulates oxygen → blood returned via veins which unite to form pulmonary veins → enter left atrium on posterior aspect of heart
systemic circulation
Blood returned from body via superior vena cava (SVC) and inferior vena cava (IVC)- higher pressure that pulmonary, deoxygenated blood drains into right atrium
cardiac cycle
- Flow into atria- continuous except when they contract, inflow leads to pressure rise
- Opening of A-V valves- flow to ventricles
- Atrial systole- completes filling of ventricles
- Ventricular systole (atrial diastole)- pressure rise closes A-V valves, opens semilunar valves (aortic and pulmonary)
- Ventricular diastole- causes closure of semilunar valves
heart sounds
1st heart sound= closing of AV valves (lub)
2nd heart sound= closing of semilunar valves (dub)
3rd heart sound= early diastole of young and trained athletes, normally absent after middle age, termed the ventricular gallop, re-emergence later in life indicated abnormality (eg. heart failure)
4th heart sound= caused by turbulent blood flow due to stiffening of walls of left ventricle, occurs prior to 1st heart sound, atrial gallop
*In tachycardia, 3+4 indistinguishable= summation gallop
stroke volume is dependant on:
- Contractility (force of contraction) eg. adrenaline increases force and stroke volume
- End diastolic volume (volume of blood in ventricle at the end of diastole)- force is stronger the more muscle fibres are stretched (within limits)
Frank- Starling Mechanism/ Starling’s Law of the Heart: stroke volume ∝ diastolic filling
Frank Starling Mechanism/ Preload is Important in:
- Ensuring the heart can deal with wide variation in venous return
- Balancing the outputs of the two side of the heart
what does the elastic arterial tree store?
pressure energy which helps maintain pressure in the arterial system during diastole (pressure drops only about a third from systolic BP)
ejection fraction
% volume pumped out, between 55 to 60% but can be 80% during exercise, in heart failure it can be 20%
- stroke volume=
volume of blood pumped by each ventricle per beat (difference between 75ml)- may double during exercise
why does systemic arterial pressure remain high during the cardiac cycle?
due to elasticity of the vessel walls and peripheral resistance
cardiac output
- volume of blood pumped per minute
- CO= HR x stroke volume
- at rest, CO= 5l/min
causes of strokes:
- cerebral infarction
- cerebral haemorrhage
- cerebral thrombosis
- cerebral embolus
- cerebral infarction
blockage of an artery, narrowing of an artery because plaques are taking up space and less oxygen and blood can move through it, can be due to due to thrombosis or embolism
cerebral haemorrhage
results reduction of oxygen to a certain part of the brain due to large occlusion of a blood vessel or an aneurysm
cerebral embolus
a part of thrombosis can break off and lodge itself somewhere else causing symptoms elsewhere eg. pulmonary embolism
what can thrombosis in the neurovascular bundle in the leg lead to?
a pulmonary embolism which can travel through the venous system
The Excitation Path
- Action potential (carried by sodium channels) then activates atria
- Atrial action potential activates AV node
- AV node- small cells, slow conduction velocity- introduces delay of 0.1 sec (delays are important to cardiac muscle but not to skeletal muscle)
- AV node activates bundle of His/ Purkinje fibres
- Purkinje fibres activate ventricles
sinus rhythm
heart rhythm controlled by SA node, rest rate approx.. 72 beats/min (wide variation)
bundle of His
Insulated connective tissue between connecting ventricles allows delays to be put into place, electrical insulator.
Cardiac muscle is myogenic-
it generates its own action potentials.
- APs develop spontaneously at the sino-atrial node
intercalated discs
adhering structures that hold individual cardiomyocytes together to form the functional syncytium that contracts rhythmically
adhering junctions in intercalated discs:
- Fascia adherins- anchor sites for actin
- Desmosomes- provide structural support and bind cardiomyocytes together to prevent separation
- Gap junctions- formed from connexins, allow action potentials to pass between cardiomyocytes
what do T tubules in the sarcolemma allow?
depolarisation of the membrane to penetrate the muscle fibre
comparison of cardiomyocyte and skeletal T tubules
cardiomyocyte T tubules are less prevalent, larger and wider
excitation- contraction couple in skeletal muscle
- Intracellular calcium release from T tubules in the SR
- Cross bridge formation and muscle contraction
- Calcium removal by calsequestrin and muscle relaxation
skeletal muscle is neurogenic
needs a nervous impulse to initiate a contraction
Action potential controls
the duration and force of contraction in the heart. Only acts as a trigger in skeletal muscle.
Increasing the action potential length = increase duration and force of contraction.
Ca induced Ca release
- The SR contains L type calcium channels that are activated in response to electrical stimuli allowing calcium to enter cardiomyocytes
- Activation also opens calcium-release channels on the SR causing release of its calcium stores
How is uptake of Ca by SR managed:
ATP driven Ca pump
Exit of Ca from cell can be through either:
- An ATP driven Ca pump (weak)
- Na-Ca exchange protein (energy from Na entry gradient)
endocrine, paracrine and autocrine hormones
Endocrine hormones- acts on distant cells/organs eg. thyroxine, calcitonin, adrenaline, oestrogen, testosterone
Paracrine hormones- acts on adjacent cells/organs eg. nitric oxide, endothelin, noradrenaline
Autocrine hormones- acts on the same cell/organ eg. endothelin, noradrenaline
classical vasoactive hormones in endocrine regulation
- ANGII
- Aldo
- noraadrenaline
- adrenaline
- arg vasopressin
- ADH
- neutretic peptides- atrial, brain
- others: relaxin, uromodulin, urotensin
renin- angiotensin system
- Kidney is sensor of BP and salt loss
1. Excess loss of salt or drop in afferent pressure cause juxtaglomerular cells produce renin
2. Renin travels in the bloodstream and causes the cleavage of angiotensinogen into angiotensin I
3. ACE further cleaves angiotensin I into angiotensin II
4. Angiotensin II stimulates the release of aldosterone from the adrenal cortex
function of ANGII
- increases the reabsorption of salt by the PCT (proximal convoluted tubule)
- activates the sympathetic nervous system centrally
- Stimulates release of aldosterone from the adrenal cortex
- Constricts blood vessels
- Influences ADH secretion
adrenaline effects on body:
Adrenaline (adrenal gland): tachycardia, increased cardiac contractility (b1), increased muscle blood flow, bronchodilation (b2), hypertension, ect.
noradrenaline effects on body:
Noradrenaline (peripheral neurotransmitter): peripheral vasoconstriction (a1), renal and splanchnic vasoconstriction, hypertension
what are natriuretic peptides? function
- Used as biomarker of heart failure- high end terminal BNP= heart failure
- Powerful natriuretic and diuretic effect in kidney
- Block production of renin and reduce production of angiotensin II
- Dilate blood vessels
- Rely on stretch receptors in heart
hormones that cause retention and excretion of body sodium
retain: ANGII, Aldo
excrete: ANP/BNP
hormones that cause retention and excretion of body water
retain: ADH/AVP
excrete: ANP/BNP
hormones that increase/decrease cardiac output
inc: AD
decrease: NA
hormones that increase/decrease BP
inc: NA, AD, ANGII, Aldo
dec: ANP/BNP
What mediators affect blood vessel tone, BP and kidney function?
ANG II/ALDO, Adrenaline, AVP, ADH, ANP/BNP
Overall cause of endothelial dysfunction
less NO generation, more ET-1
Nitric oxide generation and action
NO generation: L-arginine is converted to L-citrulline by NO synthase which gives off NO
Action: activates guanylate cyclase which produces cGMP which causes smooth muscle cells to relax by reducing availability of calcium
inhibitor of NO generation
L-monomethyl arginine
NO function
- Acts primarily on vascular smooth muscle cells
- Vasodilatory
- Anti-proliferative
- Anti-inflammatory
- Anti- platelet
Endothelin-1 generation and inhibitors
Big Endothelin-1 is cleaved by Endothelin Converting Enzyme to form Endothelin-1. This production can be blocked by an ECE inhibitor or an endothelin receptor antagonist
ET-1 functions at ETA receptor
ETA receptor • Vasoconstriction • Hypertension • Arterial stiffness • Endothelial dysfunction
ET-1 functions at ETB receptor
- Vasodilatation
- ET-1 clearance
- Natriuresis (exertion of sodium in urine)
ideal cardiac biomarker should be:
high sensitivity, hifh specificity, rapid release for early diagnosis, cost effective
homocysteine biomarker
- Linked to atherosclerosis through vascular wall damage
- May be elevated in B-vitamin deficiency: Vit B6, B9 (folate), B12
- Very high CV risk in individuals with “classical homocystinuria” = autosomal recessive
- Tends to be measured when CV disease presents in young patients in the absence of usual risk factors
high sensitivity troponin biomarker
- Protein specific to cardiac muscle
- Established use in diagnosis of myocardial infarction (MI)
- predict long-term CV risk
- Appears superior to hsCRP
how is a coronary stent placed?
Primary PCI (cardiac catheterisation)
types of CHD
angina (chronic), myocardial infarction (acute)
ACS- acute coronary syndrome: causes, presentation, types
- Myocardial infarction is a cause of the clinical presentation of ACS
- Presents with chest pain/ discomfort
- Caused by acute ischaemia, secondary to coronary heart disease
ACS includes:
• acute MI (STEMI, NSTEMI) – significant myocardial damage
• unstable angina – acute symptoms, but no significant tissue damage
why is cardiac troponin a good cardiac biomarker?
- Rapid response
- Sensitive – capable of detecting “smaller” Mis
- Best specificity for cardiac tissue
- Suitable for late presentation
troponin complex
1:1:1 complex of three regulatory proteins (TnT, TnI, TnC), exclusively present in striated muscle
• regulates the interaction between actin and myosin
• cardiac specific forms- cTnI, cTnT
what is detectable in those without myocardial damage?
• hsTnI, hsTnT
thresholds for acute MI (men and women)
34 ng/L for men, 16 ng/L for women
heart failure definition
clinical syndrome in which the heart is unable to maintain a cardiac output (CO) that satisfies the metabolic demands of the body
BNP and NT-proBNP in blood during heart failure
Levels of both in your blood go up when your heart failure gets worse and go down when it gets better.
atheroma
plaques found in elastic and medium-large muscular arteries
risk factors of atheroma
- Age
- Male sex
- Genetics
- Hyperlipidaemia
- Hypertension
- Smoking
- Diabetes mellitus
Arteries that atheromas can form in
Elastic and medium-large muscular arteries:
- Abdominal aorta
- Coronary arteries
- Popliteal arteries
- Descending thoracic aorta
thrombus definition
solidification of blood constituents that form within the vascular system during life
complications of atheroma
- Calcification
- Ulceration
- Thrombosis
- Plaque rupture
- Haemorrhage
- Aneurysmal dilation- localised swelling caused by weakening of walls
histological appearance of thrombus
alternating pale and dark lines of Zahn
arterial thrombi properties
- Usually occlusive
- May be mural- adhere to wall of artery
- Frequent in coronary, carotid cerebral and femoral arteries
where do venous thrombi usually occur?
Occurs typically in pelvis and leg veins in association with stasis
complications of thrombosis
- Occlusion of artery or vein: area becomes cold, pale, painful and eventually tissue dies & gangrene
- Embolism
deep and superficial venous thrombosis- symptoms
Superficial (saphenous)- congestion, swelling, pain, tenderness (rarely embolise)
Deep- foot and ankle oedema, may be asymptomatic and recognised only when they have embolised (to lung)
embolus definition
detached intravascular solid, liquid or gaseous mass that is carried by blood to a site distant from its point of origin
Less common/rare forms of emboli include fragments of:
- Bone or bone marrow
- Atheromatous debris
- Droplets of fat
- Foreign bodies (like bullets)
- Bubbles of air or nitrogen
types of embolism
- Pulmonary embolism
- Systemic embolism
- Amniotic fluid embolism
- Air embolism
- Fat embolism
common origins of pulmonary embolisms
thrombi within large deep veins of lower leg or pelvic veins
actions of different sized pulmonary emboli
- Large emboli may impact the main pulmonary artery or lodge at the bifurcation as a saddle embolus
- Causes circulatory obstruction and are associated with collapse and sudden death
- Smaller emboli can travel out into the more peripheral pulmonary arteries
- If of intermediate size, they may cause pulmonary infarction particularly in patients with cardiac failure
- If very small and recurrent, may lead to pulmonary hypertension
paradoxical embolism
- In presence of interatrial or interventricular defect they may gain access to the systemic circulation
microscopic appearance of emboli
same as thombi
pulmonary embolism and infarction
- Pulmonary infarction is typically haemorrhagic
- Base of the infarct faces the pleural surface
- Patients may therefore present with haemoptysis (coughing up blood) and/or chest pain (pain on inspiration)
infarct
area of ischaemic necrosis caused by occlusion of arterial supply or venous drainage in a particular tissue
5 causes of infarction
- Thrombosis and thromboembolism account for vast majority
- Vasospasm
- Expansion of atheroma
- Compression of vessels
- trauma
4 factors that influence development of an infarct:
- Nature of vascular supply- single (spleen) or dual (lung, small bowel)
- Rate of development of occlusion- rapid occlusion more likely to cause infarction
- Vulnerability of affected tissue to hypoxia- more metabolically active tissue more vulnerable eg. heart
- Oxygen content of blood- hypoxia increases risk
types of infarct
Red (haemorrhagic):
- Venous occlusion eg. torsion
- Loose tissues
- Tissues with a dual circulation eg. lung
White (anaemic)- Arterial occlusions, in solid organs eg. heart, spleen
Septic- Infected infarcts
histology of infarction (stages)
- Ischaemic coagulation necrosis (minutes-days): liquefactive necrosis in the CNS
- Inflammatory response (hours-7days)
- Reparative response (1-2 weeks)
- Scarring (2 weeks-2 months)
pressure of pulmonary and systemic circulations
Pulmonary circulation- low pressure circulation
Systemic circulation- high pressure circulation
BP=
cardiac output (CO) x peripheral resistance (PR)
Systemic hypertension definition
- Sustained resting BP above certain level
- 140/90 (depends)
- Diastolic pressure determine severity
risk factors of primary systemic hypertension
- Idiopathic (unknown cause)
- Risk factors: genetic susceptibility, high salt intake, chronic stress (excessive sympathetic activity), abnormalities in renin/angiotensin-aldosterone (renin hypertension is v sensitive to ACE inhibitors), diabetes mellitus
Causes of secondary systemic hypertension
- Renal disease: chronic renal failure, polycystic kidneys
Endocrine causes:
• Pituitary- ACTH
• Adrenal cortex- glucocorticoid; mineralocorticoid
• Adrenal medulla - catecholamines - coarctation of the aorta
- Potentially treatable- test the urine for renal!
pathology of benign and malignant hypertension
Benign hypertension- slow changes in vessels and heart with chronic end-organ dysfunction
Malignant hypertension- rapid changes in vessels with acute end-organ dysfunction, BP tends to be higher
end organ effects of hypertension
heart: cardiac failure, ischaemic heart disease
kidney: acute renal failure (malignant)
vascular: acceleration of atherosclerosis, Intimal proliferation and hyalinisation (glassy change) of arteries and arterioles
ischaemic heart disease definition and causes
- Blood supply to heart is insufficient for its metabolic demands
Deficient supply causes:
• Coronary artery disease (commonest)
• Reduced coronary artery perfusion- shock, severe aortic valve stenosis (tight) - Excessive demand: pressure and volume overload
causes of pressure and volume overload on heart
Pressure overload: eg, hypertension, valve disease
Volume overload: eg. valve disease
coronary artery disease
- narrowing or blockage of the coronary arteries
- Coronary blood flow is normally independent of aortic pressure
- Initial response to narrowing is autoregulatory compensation
- > 75% occlusion leads to ischaemia
causes of coronary artery disease
- Atheromatous coronary artery disease (most common):
• Progressive stenosis
• Haemorrhage into a plaque
• Thrombosis - Emboli eg. from inflamed aortic valve (endocarditis)
- Vasculitis- inflammation of coronary arteries
myocardial infarction
- An area of necrosis of heart muscle resulting from reduction (usually sudden) in coronary blood supply
cause of MI
rupture of atherosclerotic plaque in coronary artery due to increase in demand in the presence of ischaemia
types of chronic ischaemic heart disease
- Chronic angina- exercise induced chest pain
- Heart failure- Related to reduced myocardial function
there is usually widespread coronary artery atheroma and areas of fibrosis often present in the myocardium
what can cardiac failure lead to?
under perfusion which causes fluid retention and increased blood volume
speeds of cardiac failure
Acute heart failure- acute onset of symptoms, often with definable cause eg. myocardial infarction
Chronic heart failure- slow onset of symptoms, associated with eg. ischaemic or valvular heart disease
Acute on chronic- chronic failure becomes decompensated by an acute event
causes of heart failure
- Pressure overload
- Volume overload
Intrinsic cardiac disease:
• Ischaemic heart disease
• Primary heart muscle, pericardial & conduction system disease
• Myocarditis
left ventricular failure
- Dominated hypertensive and ischaemic heart failure
- Causes pulmonary oedema with associated symptoms
- Leads to pulmonary hypertension and eventually right ventricular failure
- Combined left and right ventricular failure= congestive cardiac failure
Right Ventricular Failure
- Secondary to left ventricular failure
- Related to intrinsic lung disease- cor pulmonale eg. COPD
clinical features of forward and backwards failure
Forward failure
• Reduced perfusion of tissues
• Tends to be more associated with advanced failure
Backward failure
• Due to increased venous pressures
• Dominated by fluid retention and tissue congestion
left and right ventricular failure clinical features
Left Ventricular Failure: - Hypotension - Pulmonary oedema - Paroxysmal nocturnal dyspnoea Right ventricular failure: - Ankle swelling - Hepatic congestion
cardiomyocytes
heart muscle cells, aligned in sheets that wrap around heart
preload definition and causes of increase in preload
Preload- volume of blood in the ventricles at the end of diastole, determined by:
- Blood volume
- Venous tone
- Capacity of venous circulation to hold blood
afterload definition and causes of increase in afterload
Afterload- resistance the heart must overcome to circulate blood in systole, determined by: - Tone in arterial circulation Increase is caused by: - SNS activation - Hypertension
Coronary artery spasm-
spontaneous spasm of smooth muscle cells in coronary artery
causes of endothelial dysfunction
- Elevated and modified low density lipoprotein eg. in familial hypercholesterolaemia
- Oxygen free radicals caused by smoking, hypertension, activated inflammatory cells
- Infection microorganisms: herpes virus, Chlamydia pneumonia, H. pylori
- Diabetes, ageing, being male
formation of atheromatous plaque
- Development of fatty streaks- foam cells are formed by macrophages taking up increased LDL oxidised by interaction with oxygen free radicals, lipids released from foam cells when they die and accumulate in subendothelial space
- Fibrous cap- growth factors released by damaged endothelial cells and macrophages cause proliferation of smooth muscle cells which cover plaque on its luminal aspect forming the fibrous cap
- Stenosis- as the volume of plaque increases, accumulated lipid bulges inwards which reduce the luminal area, point of narrowing of the vessel lumen is called a stenosis
- Plaque rupture- the fibrous cap separates plaque’s lipid core from the bloodstream but is prone to rupture, this trigger platelet activation & aggregation and thrombus formation
statins action in lipid lowering
Statins- lower cholesterol and low-density lipoproteins (LDL) eg. simvastatin
- Inhibit HMG CoA reductase- rate limiting step which reduces formation of LDL in the liver
- also increase the expression of LDL receptors, so they are cleared faster
- Additionally: improved endothelial function, inhibition of inflammation, plaque stabilization, inhibition of thrombus formation
- Side effects: muscle pain, abdominal pain or cramping
fibrates action in lipid lowering
Fibrates eg. bezafibrate, gemfibrozil, fenofibrate
- Activate intracellular PPARalpha (peroxisome proliferator receptor alpha)
- Decrease circulating VLDL and triglyceride but also increase protective HDL and LDL uptake
ezetimibe action in lipid lowering
Inhibits cholesterol absorption at small intestine by binding to NPC1L1 protein- critical mediator of cholesterol absorption in GI epithelial cells
how are Fibrates and Ezetimibe used?
with statins or as an alternative to statins
angina pectoris
intermittent chest pain caused by mismatch between demand of oxygen by the heart and supply of oxygen to the heart
causes of O2 supply increase and decrease
O2 supply decreased by:
- Coronary artery disease
- Anaemia
O2 demand increased by:
- Exercise
- Tachycardia
- Hypertension
prophylactics that reduce likelihood of angina attack:
- Targets blood vessels: longer lasting nitrate, KATP channel opener
- Targets heart: beta adrenoreceptor antagonist, calcium antagonist, ‘funny’ channel blocker
Drugs that can be taken acutely during angina attack
rest, rapid acting organic nitrate eg. Glyceryl Trinitrate
problem with use of glyceryl trinitrate and isorobide dinitrate
GT- chronic use leads to tolerance i.e. loss of responsiveness so nitrate free periods are needed
ID- can be prophylactic, nitrate free periods required
nicorandil: mechanism and effects
- Causes vasodilation by opening ATP sensitive K+ channel in smooth muscle cells
- Nitrate moiety- releases NO- in structure therefore addition vasodilator action
Effects:
- Reduces preload and afterload: O2 demand
- Dilates coronary arteries and can increase O2 supply in coronary spasm
beta blockers
Beta Blockers
- Atenolol, metoprolol, bisoprolol
- Mechanism: block beta-adrenoreceptors, reduce cardiac rate and output, block RAAS, initial vasoconstriction (ultimately vasodilate)
- Side effects: wheeze, cold peripheries, lassitude, exercise intolerance, bad dreams, impotence, heart block, diabetes
indications: AF, angina
ivabradine
Blocks funny current in sino-atrial node cells, thus reduces the rate of spontaneous depolarisation during action potential generation → reduces heart rate and therefore O2 demand
Less side effects than β-blockers, used as alternative or as adjunct to β blocker therapy
Calcium Antagonists
Calcium Antagonist eg. nifedipine, dilthiazem
- Prevents opening of voltage dependant Ca2+ channels → prevents Ca2+ entry into cardiac muscle cells from extracellular space → reduces force of contraction and therefor O2 demand
- Side effects: headaches, flushing, ankle swelling, tachycardia
thrombus formation
- Endothelial cells- produce anti-thrombotic mediators to stop blood clotting but when blood vessel walls are damaged, pro-thrombotic molecules are released
- Collagen exposure
- Platelet activation- activated when the subendothelial layer is introduced to blood which then stick to area that is damaged and to each other
- Coagulation cascade- fibrin binds and stabilises clots and stops bleeding
why are antiplatelet drugs taken
prophylactically to reduce risk of thrombus
platelet activation
- collagen exposure and thrombin= activate platelets
- Platelets release arachidonic acid from phospholipase A2 and it is a precursor for prostaglandin molecules.
- Cyclic endoperoxidase is formed from arachidonic acid by the enzyme cyclooxygenase.
- In platelets the main prostaglandin that formed is TxA2 which activates receptors on the platelets which increases the availability of calcium- enables function of platelets.
what do activated platelets do?
change shape, release contents of granules and express glycoprotein IIb/IIa receptors for attachment of fibrin from coagulation cascade to stabilise thrombus
cyclooxygenase inhibitor actions and side effect
Cyclooxygenase inhibitor eg. aspirin
Irreversible inhibition of COX, prevents formation of TxA2 & platelet activation, works because platelets have no nucleus and cannot proliferate
Side effect: stomach pain
P2Y12 inhibitor action
P2Y12 inhibitor e.g. clopidogrel, ticagrelor
Blocks effects of ADP and prevents platelet activation
coagulation cascade
When blood vessels are damaged, series of proteases activate the coagulation cascade. Factor X activates Xa which then activates prothrombin to become thrombin which activates fibrinogen to become fibrin- stabilises the clot.
what does heparin agonise?
anti-thrombin III to promote its action
warfarin targets
Vitamin K pathway
- Reduction of Vitamin K results in the carboxylation of certain factors: II, VII, IX, X
warfarin cons
- Narrow optimal range, high risk of bleeding
- Broken down in liver, enzyme induced by other drugs, environmental influences
- Blood levels must be checked regularly
warfarin clinical indications
atrial fibrillation, presence of artificial heart valve, DVT, pulmonary embolism and occasionally after myocardial infarction
what often leads to heart failure?
MI
body’s pro and anti fibrinolytic mechanisms
pro- (tissue plasminogen activator)
anti- (PAI-1 antiplasmin)
examples of inotropic agents
- Digoxin
- Dobutamine (ß1 adrenoreceptor agonist iv for rapid response), increases heart rate and contractility
actions of digoxin and digitalis
cardiac glycosides,
mechanism: blocks Na/K ATPase, slows conduction through the AV node, increased force of cardiac contraction
positive inotrope therefore increases kidney perfusion and fluid loss]
- Side effects: anorexia, nausea, vomiting, AV block, renal failure
drugs that affect RAAS in heart failure
- Renin inhibitor eg. aliskiren
- ACE inhibitor eg. enalaspril, linsopril
- angiotensin receptor antagonists eg. losartan, valsartan
function of loop diuretics
Loop diuretics eg. frusemide, bumetanide
- Impair Na+/K+/Cl- readsorption in the ascending loop of Henle
Mineralocortoid receptor antagonists function
Mineralocortoid receptor antagonists eg. spironolactone, eplerenone
- Block effects of aldosterone on NA/K readsorption
hydralazine mechanism
- Dilator that targets arteries > veins and reduces afterload
when are nitrates and hydralazine used
to treat acute heart failure or in patients with chronic heart failure who fail to respond to other drugs.
what does the progression of heart failure do to ventricles?
ventricle walls become stiffer and thicker
fibrosis
laying down of collagen, connective tissue replaces normal tissue
Important lipids in human physiology:
- Steroids; cholesterol, steroid hormones eg. testosterone
- Fat soluble vitamins: A, D, E, K
- Phospholipids
- Sphingolipids
- Triglycerides
components of lipoproteins
- Cholesterol can be free or esterified
- Phospholipids
- Triglycerides
solubility of lipids
poorly soluble in water but miscible in organic solvents
lipoproteins main types
- Chylomicrons- mostly triglycerides, biggest
- Very Low Density Lipoprotein (VLDL)- big, predominantly triglycerides
- Intermediate Density Lipoprotein (IDL)- very short lived
- Low Density Lipoprotein (LDL)- cholesterol-rich, long-lived
- High Density Lipoprotein (HDL)- small, cholesterol rich, long lived
where are lipoproteins created within?
- Small intestine (dietary lipids)
- Liver (endogenous lipids)
- These travel to peripheral tissues and back to the above tissue for storage by reverse cholesterol transport
exogenous lipid pathway
The gut secretes chylomicrons into lymphatic system and then bloodstream. Through bloodstream, they are deposited into main sites of muscle and adipose tissue. They both store fat and triglycerides, muscle can metabolise non esterified fatty acids (NEFA)- produced by breakdown of triglyceride into glycerol and fatty acid. Lipoprotein lipase acts on chylomicrons as it travels and degrades it. Chylomicron remnants are taken up by the liver.
what does blood in a test tube look like if chylomicrons are not cleared properly?
blood in test tube would separate into an opaque serum of chylomicrons and blood, this is why fasting is important before LDL samples are taken
Endogenous Lipid Pathways
VLDL from liver travels through bloodstream but can be secreted in fasting stage. It progressively gets degraded by lipoprotein lipase as it travels. It turns into an intermediate density lipoprotein, it either gets taken up by the liver or at the liver it can be broken down by the enzyme, hepatic lipoprotein lipase so IDL become LDL.
LDL function
transports cholesterol to peripheral tissue
reverse cholesterol transport
HDL is made in both liver and gut. Free cholesterol in peripheral tissue can be secreted and packaged by LCAT enzyme and included in the payload of HDL particle. HDL travels around taking up cholesterol and then returns to the liver where it is taken up. The cholesterol is stored and secreted into the gut or repackaged into a lipoprotein to be secreted
lipids and CV disease
Raised HDL-cholesterol: decreased rates of CV disease.
Raised LDL-C: increased rates of CV disease.
apolipoproteins
proteins that bind lipids to form lipoproteins. They transport lipids in blood, cerebrospinal fluid and lymph
what apolipoprotein binds chylomicrons and VLDL?
ApoB48
what apolipoprotein binds IDL and LDL?
ApoB100
what apolipoprotein binds HDL
ApoA1
lipoproteins function
- Transport cholesterol and triglycerides around the body via the circulation
triglycerides delivery
- chylomicrons, created in the gut, deliver triglycerides to muscle & adipose tissue (where converted to NEFA)
- VLDLs, synthesized in liver, also deliver triglycerides to muscle & adipose tissue (again converted to NEFA)
cholesterol delivery
- Liver is the master organ: synthesis, secretion, uptake, excretion
- Delivered to peripheral tissues via LDL
- Uptake from circulation via remnants, IDL, LDL, HDL
- Returned to liver (from peripheral tissues) via HDL
how are oxygen free radicals formed?
- glycation reactions (diabetes)
- toxins from cigarette smoke
- macrophages
what can high conc of LDL lead to
formation of fatty streaks: LDL + monocytes + O-free radicals
familial hypercholestrolaemia
- Autosomal dominant
- Mutation in LDL receptor (or ApoB, PCSK9)
- High LDL-C levels (typically >4.9 mmol/L)
- Untreated leads to premature CHD onset
- Statin treatment shown to reduce CVD risk
Routine laboratory measurements of lipids:
- total cholesterol
- HDL cholesterol (HDL-C)
- triglycerides
- LDL is calculated by friedelwald equation (not measured)
MI acute treatment
- reperfusion via primary PCI
- drug-eluting stents (anti-proliferative agent so prevents re-occlusion)
primary prevention of CVD
- diet- reduce saturated fats, simple carbs, salt
- aerobic exercise
- aim for BMI 20-25
- reduce alcohol
- quit smoking
drugs for secondary prevention of CVD
- ACE-inhibitor, Beta-blocker – reduce post-MI mortality
- Aspirin + Clopidogrel – reduce CVD recurrence & mortality
- Statins – reduce CVD recurrence & mortality
effect of statins and ezetimibe on LDL-C
- Reduce LDL-C
- Lower risk of coronary heart disease
PCKS9 inhibitors
- monoclonal antibodies that are delivered by fortnights s/c injection
- Capable of ~60% reduction of LDL-C (as adjunct to statin)
regulation of the coagulation cascade
- TF-2a complex/f10a inhibited by TFPI, tissue factor pathway inhibitor of extrinsic
- Thrombin and f10a activity inhibited by Antithrombin pathway
- Protein C pathway inhibits activation of f5a and f8a
risk factors of venous thromboembolism
- Age
- Obesity
- Varicose veins
- Previous VTE
- Family history of VTE
- opophilia- high risk would be anti-thrombin deficiency
- Cancer
types of VTE
- DVT
- Pulmonary embolus
- Cerebral, mesenteric, axillary, splanchnic, splenic
clinical features of Lower Limb DVT
- Pain, swelling, increased temp of limp, dilation of superficial veins
- Usually unilateral
- May be bilateral if thrombosis sited in vena cava
well’s score
- Stratify patients into low, intermediate and high probability categories for VTE
testing for DVT
- Most useful objective objective tests are compression USS and D-dimer
- Venous ultrasonography
- Non- compressibility of the common femoral vein or popliteal vein are diagnostic of DVT
- Contrast venography
Clinical features of PE
- Collapse, faintness, crushing central chest pain
- Pleuritic chest pain
- Difficulty breathing
- Haemoptysis
- Exertional dyspnoea
diagnosis of PE
- CXR- to exclude any other pathology
- ECG
- Arterial blood gases
- Echocardiogram- look for right ventricular strain
types of anticoagulant therapy
- Rapid initial anticoagulation
- Parenteral anticoagulant: heparin, low molecular weight heparin, fondaparinux, OR
- Direct oral anticoagulant - Extended Therapy
- Orally active anticoagulant: Vitamin K antagonist (warfarin)
- Or direct anti oral coagulant
direct oral anticoagulants
- Dabigatran, Rivaroxaban, Edoxaban & Apixaban
- Enables rapid initial anticoagulation orally
- Continue a maintenance dose for 6 months or longer for secondary prevention of VTE
- Apixaban and Rivaroxaban do not need any overlap with heparin – big advantage in outpatient setting
thrombophilla signs
- Venous thrombosis <45 yrs
- Recurrent venous thrombosis
- Family history of unprovoked thrombosis
- Combined arterial and venous thrombosis
types of heparins
Unfractionated- Sulphated glycosaminoglycan, binds to plasma proteins, heterogenous group of molecules with MW from 3000 to 30,000D
LMW- Binds to unique pentasaccharide on antithrombin and potentiates its inhibitory action towards factor Xa and thrombin, reduced capacity to inhibit thrombin compared with UFH, predictable anti-coagulant response and dose-dependent renal clearance
when is UFH used?
- Used when there is a high risk of bleeding
- Reverse by d/c infusion and also protamine
- Monitoring required
- Risk of osteoporosis, heparin-induced thrombocytopenia (HIT)
LMWH properties
- Irreversible
- Nearly 100% bioavailability means reliant dose dependant coagulant effect
- Generally no monitoring required
- Reduced risk of osteoporosis and HIT
direct oral anticoagulant indications
- Treatment of DVT and PE
- Prevention of cardioembolic events in patients with atrial fibrillation
prevention methods of venous thromboembolism
- Mechanical: mechanical foot pumps, graduate compression stockings
- Pharmacological: LMWH, UFH, fondaparinux, dabigatran, rivaroxaban, warfarin
benefits of DOACs over warfarin
- More predictable anticoagulant profile
- Fewer drug and food interactions
- Wider therapeutic interactions & window
- Oral administration
- No need for monitoring
what stabilises a platelet thrombus?
conversion of fibrinogen to fibrin by thrombin and polymerisation of fibrin
Thrombocytopenia caused by
Bone marrow failure Peripheral consumption (eg. immune TP, DIC, drug-induced)
clinical features of Thrombocytopenia
- All give rise to a prolonged bleeding time
- Reduced number of platelets
reasons for abnormal Platelet Function:
- Most commonly drugs such as aspirin, clopidogel
- Renal failure: uraemia
reasons for Abnormal Vessel wall:
- Scurvy
- Ehlers Danlos syndrome
- Henoch Schӧnlein purpura
- Hereditary Haemorrhagic Telangiectasia
disease that causes abnormal Interaction between Platelets and Vessel Wall
Von Willebrand disease
drugs that inhibit platelet function
- Aspirin and COX inhibitors
- Reversible COX inhibitors
- Dipyridamole- inhibits phosphodiesterase
- Thienopyridines- inhibit ADP- mediated activation eg. clopidogrel
Prothrombin Time
- Measured in secs
- Reflects extrinsic and common pathways
Activated Partial Thromboplastin Time
- Measured in secs
- Reflects the intrinsic and common pathways
Measurement of fibrinogen (g/L)
- Reflects the functional activity of the fibrinogen protein
haemophilia A
- X linked recessive disorder (typically expressed in males and carried in females)
- Most cases due to sporadic mutation
- Deficiency of fVIII (or dysfunction)
- Severity of haemophilia same in different generations
- Normal fVIII level ranges from 50-150% but mild form of haemophilia is below 30%
Traditional Management of Haemophilia
- Supportive measures: ice, immobilisation, rest
- Replacement of missing clotting protein:
• Coagulation factor concentrates
• Desmopressin used to increase factor VIII levels in mild/moderate haemophilia A
• Novel therapies- monoclonal antibodies, knock-out AT - Antifibrinolytic Agents: tranexamic acid
Congenital Vs Acquired Haemophilia
Congenital: hemarthroses, muscle bleeds, soft tissue bleeds
Acquired: large haematomas, gross haematuria, cerebral haemorrhages, compartment syndromes
Roles of Von Willebrand Factor
- Promote platelet adhesion to subendothelium at high shear rates
- Carrier molecule for FVIII
- Most common heritable bleeding disorder- mainly autosomal dominant
- Variable reduction in factor VIII levels- mucocutaneous bleeding including menorrhagia, post-operative and post partum bleeding
Management of Von Willebrand Disease
- Antifibrinolytics- tranexamic acid
- DDAVP (for type 1 vWD)
- Factor concentrates containing vWD
- Contraceptive pill for menorrhagia
acquired coagulation disorders
- Underproduction of coagulation factors- liver failure or Vit K deficiency
- Immune: acquired haemophilia, acquired VW syndrome
- Consumption of coagulation factors: DIC
liver disease and coagulation disorder
- Reduced hepatic synthesis of clotting factors
- Thrombocytopenia secondary to hypersplenism
- Reduced vitamin K absorption due to cholestatic jaundice causing deficiencies of factors II, VII, IX & X
- Treat with plasma products and platelets to cover procedure and Vit K
DIC
- Acquired syndrome of systemic intravascular activation of coagulation
- Widespread deposition of fibrin in circulation
- Tissue ischaemia and multi-organ failure
- Consumption of platelets and coagulation factors to generate thrombin may induce severe bleeding
- To maintain vascular patency, plasmin generated in excess leads to fibrinogenolysis
causes of DIC
- Sepsis
- Tumour
- Pancreatitis
- Transfusion of ABO incompatible cells
DIC coagulation features
- Prolonged prothrombin time
- Prolonger activated partial thromboplastin time
- Low fibrinogen
(markers of consumption of coagulation factors)
• Raised D dimers (marker of increased fibrinolysis)
Ventricular contraction and relaxation
- Ventricular contraction- contraction of ventricles pushes blood into elastic arteries causing them to stretch
- Ventricular relaxation- elastic recoil in the arteries maintains driving pressure during ventricular diastole
stiff large arteries and BP
- Cause a higher systolic BP leading to higher stroke and MI risk
- Cause a lower diastole BP reducing coronary artery filling
genetics of BP
- 30-50% genetic heritability
- Genes are mostly found in the kidney
- Affect movement of electrolytes in and out of kidney so salt handling in the kidney is critical for high blood pressure
prioritise BP treatment for
- Older people (50+)
- Diabetics
- People with other CVS risk factors (lipids, smoking ect.)
stages of high BP
Stage 1: Clinic BP >140/90
Stage 2: Clinic BP >160/90
Stage 3: Clinic BP >180/110
calcium antagonists reduce symptoms in
angina and isolated systolic hypertension
- Diuretics (thiazide-like) have benefits in
heart failure
ACE inhibitors
- Enalapril, lisinopril, ramipril
- Mechanism: inhibit ACE, block RAAS, increase bradykinin, dilate arteries (and veins)
- Side Effects: cough, renal dysfunction, dizziness, rash
thiazide drugs mechanism
mechanism: inhibit Na+/Cl- symport, distal tubular natriuresis, dilates arteries and veins
drug related secondary causes of BP
- Oestrogen oral contraceptives
- Liquorice/ carbenoxolone/ steroids
- Non-steroidal anti-inflammatory (NSIADs)
- Sympathomimetics including cocaine
- Alcohol
what does he foetal ductus venosus become in adults?
ligamentum venosum
combo of which 2 drugs can cause asystolic cardiac arrest?
beta-blockers and calcium channel blockers
what is spontaneous activation of the sinus node caused by?
leak of calcium into the sinus node
effect of sympathetic nerves on heart
Sympathetic nerves release adrenaline onto the surface of the heart which can increase the depolarisations and the contractility of the heart.
effect of parasympathetic nerves on heart
Parasympathetic nerves come into the heart from the brain stem and the vagus nerves innervate the heart as well as other structures in the body. When these nerves are active, they slow the heart down.
parasympathetic and sympathetic systems at rest and exertion
In the resting state, the parasympathetic system is active and the sympathetic isn’t.
While exercising, the parasympathetic system becomes inactive and that causes an increase in heart rate where the sympathetic system becomes active.
impulse propagation in the heart
The sinus node activates and causes a ripple effect through the atria.
The AV valves which are between the atria and ventricles (mitral valve- left, tricuspid valve- right) are made of fibrous tissue that doesn’t conduct electrical signals so there is no way for electrical impulse to pass from atria to ventricles other than the AV node.
The AV node conducts slowly compared with the rest of the heart which introduces a 0.15s time delay between atrial contraction and ventricular contraction, this gives time for the atria to contract and ventricles to fill with blood before contracting and deliver blood to body/lungs.
Once the impulse reaches the ventricles, rapid conduction is achieved through the bundle of His, the right/left bundle branches and the Purkinje fibres.
This allows the ventricles to contract simultaneously giving a good cardiac output.
why is the PR interval small?
because the atrial muscle doesn’t have a lot of muscle mass.
what does the QRS complex reflect
ventricular contraction
- Large QRS complexes- large ventricular mass like in high BP
- Wide QRS complexes- taking longer than normal for ventricular activation, could be problem with smaller fibres (eg. His, Purkinje, bundles)
what does the T wave reflect
ventricular repolarisation
sinus arrhythmia
- Sinus node fires at a variable rate
- Speeds up during inspiration and slows down during expiration
- Effect caused by variations in vagus nerve activity
sinus tachycardia and causes
- Sinus node fires >100 per minute
- Physiological causes: anxiety, exercise
- Pathological causes: fever, anaemia, hyperthyroidism, heart failure
sinoatrial disease
- Degenerative disease where healthy muscle around sinus node is replaced by scar tissue, fibrous tissue and fatty tissue
- Mixture of sinus tachycardia, bradycardia and atrial ‘ectopic’ beats, atrial fibrillation
treatment of sinoatrial disease
- Permanent pacemaker to prevent slow rhythms
- Antiarrhythmic drugs (eg. digoxin, amiodarone) to prevent rapid rhythms
Sinus Bradycardia and causes
- Sinus node fires <60 beats per minute
- Physiological causes: sleep, athletes
- Pathological causes: hypothyroidism, hypothermia, sinus node disease raised intracranial pressure
AV nodal blocks- types and features
- Long PR interval- issue with AV nodal conduction
- First degree AV nodal block- delay to conduction in AV node
- Second degree AV nodal block: Wenckebach conduction- PR interval gradually increases, leads to pauses in ventricular rhythm,
- Sometimes QRS complex can be dropped which indicates problems with bundle of His
causes of AV nodal block
• Sino-atrial disease • coronary heart disease • aortic valve disease • drugs – beta-blockers – digoxin – calcium channel blockers
treatment of AV nodal block
- remove any triggering cause eg. drugs
- atropine or isoprenaline (acute treatment)
- permanent pacemaker
atrial fibrillation and flutter
- irregularly irregular rhythm
- Apical radial deficit- every time the aortic valve closes, sometime a pulse won’t be felt (too little blood pushed out)
- atria contract at rapid and uncoordinated manner
- some people who are prone to atrial fibrillation are also prone to atrial flutter- regular rapid activation of atria
Causes of Atrial Flutter/ Fibrillation:
- Sino atrial disease
- Coronary heart disease
- Valve disease (esp. mitral valve)
- Hypertension
- Cardiomyopathy
treatment of atrial fibrillation and flutter
- Drug to block AV node and therefore limit heart rate eg. digoxin or beta blocker
- Electrical cardioversion
- Catheter ablation- wires into heart to target tissue that cause atrial fibrillation
ventricular fibrillation
- Heart rate over 150 beats
- Broad complex (wide QRS complex) tachycarida- originates from the ventricles
- In most cases, can be life threatening
treatment of ventricular fibrillation
- Defibrillation
- Anti-arrhythmic drugs
- Remove any triggering cause
- Implantable defibrillator for some patients
anastomoses
connections between diverging blood vessels
what can compensate for occlusion of the main system in some circumstances?
Collateral circulation
dilated artery= narrowed artery= split artery= blocked artery= inflamed artery= oversensitive artery=
o Dilated= aneurysm o Narrowed= stenosis o Blocked= occluded • Split= dissection • Over sensitive= vasospasm • Inflamed= vasculitis
aneurysm
- Defined by arteries being 1.5 times the normal diameter
- Degenerative aneurysms are the most common- occur when the connective tissue and muscular layer of the aorta weakens and gets thinner, which increases the chances that it will rupture or dissect, happens most often in descending thoracic aorta or abdominal aorta
stenosis
- Atherosclerosis, also leads to occlusion after plaque rupture
symptoms: - Claudication- pain on walking a fixed distance which is worse uphill, eases rapidly when you stop, angina of the leg
- Short distance claudication
- Nocturnal pain/ rest pain
treatment of claudication
- Quit smoking
- Aspirin
- Atorvastin
acute symptoms of occlusion (6Ps)
- Pain (sudden onset)
- Palor- extreme or unnatural paleness
- Perishingly cold
- Parasthesia- abnormal sensations of skin
- Pulselessness
- Paralysis
chronic symptoms of occlusion
- Short distance claudication
- Nocturnal pain
- Pain at rest
- Numbness
- Tissue necrosis
vasospasm
- Overactive vasoconstriction
- Capillary beds shut down
- Triggers- cold, stress
- Can have underlying connective tissue disease
vasculitis
- Large vessel: Takayasu’s disease, ‘the pulseless disease’
- Medium vessel: Giant cell arthritis/ polymyalgia
- Small vessel: lots of polyangiitis conditions usually involving kidney
treatment of vasculitis
steroids or other immunosupressants
broken artery causes
trauma, self-inflicted, latrogenic (due to physician or therapy)
diabetic foot
- Neuropathic
- Ischaemic
- Infected
- Calcified vessels
- Small vessel arterial disease
- Can’t see their own foot (retinopathy)
Charcot foot (end stage diabetic foot changes)
o Neuropathic
o Warm (>2C than normal)
o Multiple fracture
o “Rocker bottom” sole
Valve Failure in superficial and deep veins
- Superficial veins= varicose veins
- Deep veins= venous hypertension
venous hypertension symptoms
- Hemosiderin staining
- Swollen legs
- Itchy, fragile legs
- Gaiter distribution (shinpad)
- Risk of ulceration
treatment for venous hypertension
- Emollient to stop skin cracks
- Compression: bandages, wraps, stockings
- Elevate and mobilise
Phlegmasia and Venous Gangrene
- Phlegmasia= rare form that results from extensive thrombotic occlusion
- Often with underlying cancer
- Treatment: thrombolysis
Porto-systemic venous system
- Mesenteric or ‘portal venous’ drainage is via the liver before the heart
- Systemic circulation is returned to the heart directly
- The two circulation systems combine at a number of points
portal hypertension development and body’s recovery
In liver disease the portal system fails to drain and portal hypertension develops. Blood is therefore diverted into the systemic venous system → Porto-systemic venous anastomoses
where does the lymphatic system drain?
thoracic duct and ultimately to left subclavian vein
lymphoedma cause
Under normal circumstances the lymphatic system collects interstitial fluid and ultimately returns to the circulation. If the lymphatic channels are blocked interstitial fluid accumulates which leads to lymphoedema.
Lymphoedema Treatment
- Compression
- Skin care
- Exercise
- Manual lymphatic drainage: specialised massage technique
- Rarely surgery to debulk, liposuction or connecting lymph channel to veins
causes of reduced oncotic pressure
- Liver failure
- Renal disease- low protein or too much water
- Malnutrition- kwashiorkor (severe protein malnutrition- oedema)
Low protein (albumin) states lead to limb swelling and oedema.
starling forces
the forces created by the hydrostatic and oncotic pressure due to blood and extracellular fluid
- Hydrostatic= out of the capillary. Greater at the arteriole side of the capillary
- Oncotic= into the capillary. Greater at the venule side of the capillary
movement of water due to interstitial pressure (each have an effect on the tendency for water to move into or out of the capillary)
- The hydrostatic pressure of blood forces water out of the capillary
- The hydrostatic pressure of interstitial fluid tends to draw water out of the capillary
- The oncotic pressure of plasma draws fluid into the capillaries
- The oncotic pressure of interstitial fluid draws water out of capillaries
filtration and reabsorption in capillary fluid exchange
- At the arteriole end, high blood pressure is greater than osmotic pressure and fluid is forced out resulting in high solute concentration in the blood (FILTRATION)
- At the venule end, blood pressure is low as blood has been diverted to many arterioles and osmotic pressure (
in what way can the Starling equilibrium be disturbed to allow water accumulation in the interstitial space?
net capillary filtration exceeds capacity for lymphatic drainage
factors that increase net filtration
- Increased hydrostatic pressure- favours filtration over absorption
- Decreased oncotic pressure- reabsorption is reduced and net filtration is increased
- Increased capillary permeability- results in loss of protein from the plasma into the interstitial space which increases oncotic pressure and promotes net filtration
arterial blood pressure=
CO x SVR (Systemic Vascular Resistance)
SVR- majority of vascular resistance is provided by arterioles, change in tone of smooth muscle results in blood flow to be diverted from one vascular bed to another
causes of increase in myocardial contractility
Myocardial Contractility
Increased by: noradrenaline, adrenaline, beta-1 adrenoreceptors
cause of cardiac arrhythmia
physiological:
1. Increase in automaticity: cells that are normally quiescent starting to depolarise spontaneously
2. Re-entry: re-entry of the wave of depolarisation back to higher levels allowing rapid circus movement (rare)
Clinical: drugs, electrolyte imbalance, coronary heart disease leading to ischaemia within the conduction system and myocardium, congenital
what is blood vessel smooth muscle directly innervated by?
post-ganglionic sympathetic nerve endings which release noradrenaline to act as an antagonist at alpha-1 adrenoreceptors and cause vasoconstriction.
Some muscles cause vasodilation by acting at beta-2 adrenoreceptors.
Smooth muscle tone is under influence of
locally secreted factors like endothelin (vasoconstrictor) and NO (relaxer).
arterial baroreceptors are
Specialised mechanoreceptors that respond to stretch in the adventitial layer or the artery by producing action potentials
sites of arterial baroreceptors
- carotid sinus- signals travel in glossopharyngeal nerve, can sense ABP seen by cerebral circulation
- aortic arch- signals travel in vagus nerve, can sense ABP seen by heart and other major organs
what can BP be increased/decreased by?
increased by the vasoconstrictor phenylephrine.
reduced by the vasodilator glyceryl trinitrate.
where do baroreceptor signals travel to
vasomotor centre in the medulla oblongata that is responsible for homeostatic reflexes
Many efferent responses are coordinated by the autonomic nervous system.
baroreflexes
provide second to second control of blood pressure
Baroreflexes can be tested using tilt table testing where rapid movement from the lying position require prompt increases in heart rate to maintain blood pressure
baroreflexes in young vs old
extremely sensitive in younger individuals allowing them to withstand changes in posture without threatening blood pressure and immediate cerebral perfusion
elderly have less sensitive baroreflexes: less able to increase heart rate to maintain blood pressure, less able to tolerate sudden changes to systolic blood pressure
Hypertension means that baroreflexes must reset to allow base blood pressure at a higher point.
supreventrivcular tachycardia presentation
- Palpitations
- Rapid regular pulse (160-180/min)
- Often in young patients
Problem: rapid re-entry through the AV node
supreventrivcular tachycardia management and prevention
- Vagal stimulation manoeuvres- carotid massage, Valsalva, eyeball pressure, diving reflex
- Immediate treatment: adenosine, verapamil, synchronised DC cardioversion (if drugs fail and rapid control required)
- Prevention: verapamil orally, surgical ablasion (normalises heart rate)
adenosine
- Natural endogenous purine
- Mechanism: a1 receptors in the AV node (K+ channels), hyperpolaristion of conduction tissue, transient blockage of conduction through the AV node, temporarily abolishes re-entry through the AV node
- Indications: supraventricular tachycardia
- Side effects: chest pain dyspnoea, dizziness, nausea
verapamil
- Calcium channel blocker
- Mechanism: blocks voltage sensitive L type calcium channels, lower conduction through the SA and AV nodes, lower force of contraction of heart, vasodilation
- Indications: SVT, AF, angina, hypertension
ventricular tachycardia
- Series of 3 or more ventricular ectopic beats
- Increase in automaticity of ventricular tissue
- Serious- often causes significant haemodynamic disturbance with hypotension, heart failure
- May deteriorate to cardiac arrest
- Cause: myocardial ischaemia (reperfusion)
amiodarone
- Class III anti-arrhythmic drug
- Mechanism: prolongs cardiac action potential, blocks potassium channels
- Indications: highly effective multipurpose antiarrhythmic, atrial and ventricular arrhythmias
- Side effects: toxic, reversible corneal microdeposits, photosensitivity, pulmonary fibrosis, hepatitis, thyroid dysfunction
treatment of complete heart block
pacemaker, atropine
streptokinase
thrombolytic medication, which breaks down clots. It may be used in myocardial infarction, pulmonary embolism or ischaemic/thromboembolic stroke.
tetralogy of fallot
ventricular septal defect , pulmonary valve stenosis, a misplaced aorta and a thickened right ventricular wall
which factors relax blood vessels by generating NO?
Sheer stress/blood flow, acetylcholine, bradykinin and Substance P all relax blood vessels by generating NO.
what kinds of plaques are at greatest risk of rupture?
Plaques which have a thin fibrous cap, large lipid pool and large inflammatory cell infiltrate are at greatest risk of rupture.
Treatment for varicose veins
endothermic ablation, surgical removal, foam sclerotherapy, adhesive occlusion, compression
cardiac rupture sequence of events after MI
weakening of wall by necrosis -> cardiac rupture -> haemopericardium -> cardiac tamponade -> cardiac arrest
pericarditis after MI
causes sharp chest pain and normally occurs within 2-4 days
