RCM Week 6 (hypertension) Flashcards
What are the physical laws governing pressure / flow relationships in blood vessels
Blood is not a simple ‘Newtonian’ fluid: red and white cells, platelets, lipids are suspended in a solution of proteins
Blood vessels are not uniform, straight, rigid tubes: vessels are multibranched with variable elasticity and variable diameters
How do you calculate flow
Flow = pressure gradient / resistance
Pressure gradient : between arteries and veins : created by pumping action of the heart
Resistance: a measure of the degree to which the tube (blood vessels) resists the flow of liquid (blood) through it
What is the size order of the individual vessel diameters
Aorta > arteries > arterioles > capillaries
capillaries < venules < veins
What is the size order of the total cross sectional areas
Aorta < arteries < arterioles < capillaries
Capillaries > venules > veins
What determines flow
Flow - directly related to pressure difference
- inversely related to length of tube
- inversely related to viscosity of fluid
- directly related to radius of tube
How do you calculate resistance
Pressure difference / flow
How do you calculate total peripheral resistance
Arterial - venous P / cardiac output
How do you calculate renal vascular resistance
Arterial - venous P / renal blood flow
Which factors determine resistance
Directly related to length of vessel
Directly related to viscosity of fluid
Inversely related to vessel radius
Reduced diameter = increased resistance
What does blood vessel radius depend on
Active tension exerted by smooth muscle (vascular smooth muscle)
Passive elastic properties of wall (elastin and collagen)
Blood pressure inside vessel
What is the law of Laplace
Distending pressure = wall tension / radius
What happens during vasoconstriction and vasodilation
Vasoconstriction - increased active tension, decreased passive tension
Vasodilation - decreased active tension, increased passive tension
Factors affecting vascular smooth muscle contraction
Hormones eg catecholamines (noradrenaline, adrenaline : constrict / dilate)
Peptides :
Vasopressin, angiotensin (constrict)
Bradykinin (dilate)
How much of the cardiac output goes to the skin
4% cardiac output at rest in thermoneutral environment (can vary between 1 and 200 ml / 100g/min )
Describe the neuronal control of blood flow to the skin
Arterioles have a relatively weak innervation (a vasoconstriction) A-V anastomoses have a dense innervation (a vasoconstriction)
- increase in core temperature causes AVAs to dilate increasing skin blood flow and hence heat loss
How is blood flow to the skin controlled by local mechanisms
Arterioles show some degree of myogenic autoregulation. A-V anastomoses show no autoregulation and no reactive hyperaemia. Endothelin may be involved in pathological states (raynauds)
How is blood flow to the skin controlled by hormones
Angiotensin, vasopressin, noradrenaline, adrenaline all cause vasoconstriction
Describe the special features of the skin in terms of blood flow
Primary function is thermoregulation. Sweat glands have sympathetic cholinergic innervation (sudomotor) which can cause vasodilation via release of eg bradykinin
How much of cardiac output does skeletal muscle receive
15% at rest ( can vary between 3 and 60 ml / 100g/ min)
What are the neural influences of blood flow to the skeletal muscle
Important a vasoconstriction, some B vasodilation, maybe sympathetic cholinergic vasodilation
Involved in systemic BP regulation. Skeletal muscle is about 40% of body mass hence vasoconstriction has large influence on TPR
What are the local influences of blood flow to skeletal muscle
Rest: neural control (baroreflexes) over-ride autoregulatory mechanisms
Exercise: local metabolites have a major influence (K+, adenosine, lactate etc)
Special features of skeletal muscle in terms of blood flow
Capacity to increase flow in exercise (20-fold)- active hyperaemia. Large increase in flow post occlusion- reactive hyperaemia
What is hyperaemia
Increased blood flow
How much of the cardiac output does the kidney receive
25%
What is the neural role of blood flow to the kidney
Important a vasoconstriction; some B vasodilation. Renin secreting cells have a sympathetic innervation (B adrenoceptors)
What is the hormonal influence on blood flow to the kidneys
Noradrenaline, adrenaline, angiotensin can cause constriction. Vasopressin may cause vasodilation via prostaglandin / NO release. Dopamine causes vasodilation
What are the special features of the kidney in regard to blood flow
Excretory function of the kidney depends on well maintained flow (autoregulation). Vascular connections provide for capacity to regulate afferent / efferent resistances
How much cardiac output do the lungs receive
100%
What are the local influences on blood flow to the lungs
Unlike elsewhere, hypoxia causes vasoconstriction which is augmented by hypercapnia - possibly mediated by endothelin. NO causes dilation - may be used therapeutically
Pulmonary hypertension - possible therapeutic strategies include endothelin receptor antagonism and NO inhalation
What are the mechanical influences on blood flow to the lungs
Flow is affected by changes in alveolar pressure and lung volume. Increase in flow (cardiac output) associated with recruitment and distension of micro vessels and a decrease in vascular resistance
If alveolar pressure > intravascular pressure, flow is reduced. Lung inflation reduces resistance in extra- alveolar vessels (traction) and increases resistance in intra-alveolar vessels (compression)
Special feature of the lungs in relation to blood flow
Thin walled vessels with low resistance, low vasoconstrictor capacity. Hydrostatic pressure < colloid osmotic pressure which favours reabsorption
Hydrostatic pressure = 10mmHg
Colloid osmotic pressure = 25 mmHg
What is white coat hypertension
There is good evidence that the stress of visiting the GP can increase blood pressure leading to false diagnosis
Home monitoring and ambulatory devices are now more widely used to give a more realistic picture
What is systolic BP determined by
Stroke volume - increase StV, increase SBP
Aortic elasticity - decrease elasticity, increase SBP
Why does decreased elasticity increase systolic BP
Because normally elastic aorta take up kinetic energy from blood during systole and dampens the rise in pressure. Inelastic aorta may cause systolic hypertension in the elderly
What is diastolic BP determined by
Peripheral resistance: increase TPR, increase DBP
Aortic elasticity : decrease elasticity, decrease DBP
Heart rate: decrease HR, decrease DBP
Why does decreased aortic elasticity decrease diastolic BP
Kinetic energy taken up during systole is given back in diastole, adding to the pressure. If less is taken up there is less to give back, causing wide pulse pressure in the elderly
How do you calculate mean arterial BP
Cardiac output x total peripheral resistance
What are the estimates for mean arterial blood pressure, cardiac output and total peripheral resistance in systemic circulation
MAP- 100mmHg
CO- 5 L/min
TPR- 20 units (mmHg / litre / min)
What are the estimates of mean arterial blood pressure, cardiac output and total peripheral resistance in pulmonary circulation
Mean pulmonary arterial pressure - 10mmHg
CO (right heart) - 5 L/min
Pulmonary vascular resistance - 2 units
Why is control of arterial blood pressure important
Because it provides a pressure head to drive blood flow, permits activity, postural changes - protects against effects of gravity. This is achieved by: Pressure sensors (in circulation) Integration centres (in CNS) Effector mechanisms (via autonomic nervous system)
What are baroreceptors
Pressure sensors
1) arterial (high pressure) baroreceptors- located in walls of carotid sinus and aortic arch
What are effector mechanisms
Autonomic control of the circulation
Heart:
- parasympathetic (acetylcholine, muscarinic receptors, decrease HR)
- sympathetic (noradrenaline, B1-adrenoceptors, increase HR and force (StV)
What are cardiopulmonary receptors
Low pressure baroreceptors located in pulmonary vasculature, atrial-vena caval junctions, ventricular walls
Increase in transmural pressure- increase in afferent nerve discharge (vagus)
Describe blood flow velocity in capillaries
It is not uniform- depends on contractile state of arterioles / pre-capillary vessels
Can vary from 0 to 8mm/sec (average 1mm/sec)
Describe solute / solvent movement across capillaries
Is not uniform
- depends on the permeability which can vary between tissues, within tissues at different times and along the capillary bed
- determined by diffusion ; filtration ; pinocytosis
What is fick ‘s law
J = -PS (Co-Ci)
J- quantity moved per unit time
P - capillary permeability to the substance
S- capillary surface area
C- concentration outside (o) and inside (i)
What are filtration and reabsorption favoured by
Filtration:
1) capillary hydrostatic pressure (Pc)
2) interstitial fluid colloid osmotic pressure
Reabsorption
1) capillary (plasma) colloid osmotic pressure
2) interstitial fluid hydrostatic pressure
What is capillary hydrostatic pressure (Pc)
Major determinant of fluid movement
Depends on: pre / post capillary resistances Venous pressure (arterial pressure)
If an arteriole constricts :
Increase pressure upstream, decrease pressure downstream so precapillary constriction reduced Pc
What is interstitial fluid colloid osmotic pressure
Normally a minor determinant of fluid movement depends on the presence of protein in interstitium hence capillary permeability to protein - normally very low
What is capillary colloid osmotic pressure
Major determinant of fluid movement depends upon:
Synthesis / breakdown of protein (liver)
Capillary permeability to protein
Abnormal protein loss (kidney damage)
What is interstitial fluid hydrostatic pressure
Normally a minor determinant of fluid movement
Depends upon:
Interstitial fluid volume
Compliance of organ
Effective drainage
Describe lymphatic system and vessels
Lymphatic system provides drainage
Lymphatic vessels are valves and highly permeable to protein
Lymph flow rate - 2-4 litres / day - returns excess filtered fluid and 95% of protein lost from vascular system back to the circulation (subclavian vein)
What is an oedema
Excessive tissue fluid formation that will result in swelling
What are possible causes of oedema
Lymphatic obstruction (reduced drainage)
Increased venous pressure (congestion)
Hypoproteinaemia (eg renal damage)
Hypervolaemia
Inflammation (vasodilation and increased permeability)
Define hypertension
A blood pressure which is associated with significant cardiovascular risk
What can secondary hypertension be due to
- renal disease
- renovascular disease
- conns syndrome (too much aldosterone)
- Cushing’s syndrome
- hyperthyroidism
- phaeochromocytoma - catecholamine secreting tumour
- pregnancy
- drugs (eg NSAIDs, corticosteroids, sympathomimetics)
Causes of essential hypertension
Thought to be due to interaction of a range of causes
- obesity : production of angiotensin from adipocytes
- insulin resistance (‘metabolic syndrome’)
- excessive alcohol consumption
- genetics
- environment ?
- fetal programming : low birth weight?
- salt sensitivity
- ethnicity
- age
Goals of treatment of hypertension.
- reduction in cardiovascular damage
- preservation of renal function
- limitation or reversal of left ventricular hypertrophy
- prevention of ischaemic heart disease
- reduction in mortality
How do you calculate blood pressure
Cardiac output x total peripheral resistance
What is the role of ACEIs
By inhibiting the ACE, they lead to reductions in angiotensin II which leads to:
- reductions in arterial and venous vasoconstriction
- reduced aldosterone production leads to reductions in salt and water retention
- also potentiate bradykinin - cough
- may increase potassium
- best at decreasing nephropathy in pts with diabetes
Why should ACEIs be avoided in renovascular disease
Renin- dependent hypertension, ACEIs lead to renal underperfusion and severe hypotension
What are vasodilators
Calcium channel inhibitors
- inhibit voltage operated Ca2+ channels on vascular smooth muscle (leading to vasodilation and a reduction in BP)
What is the role of diuretics
Inhibit Na+ / Cl- in distal convoluted tubule
- reduction in circulating volume
Important side effects:
- hypokalaemia
- postural hypotension
- impaired glucose control
What is the role of alpha-blockers
These are competitive receptor antagonists of a1- adrenoceptors
- last choice antihypertensives due to widespread side effects
Adverse effects of ACEIs
- cough
- severe first dose hypotension
- renal damage
Adverse effects of calcium channel blockers
- peripheral oedema (swollen ankles)
- postural hypotension
- constipation (some)
Adverse effects of thiazides
- diabetogenic
- alter lipid profile
- hypokalaemia
- postural hypotension
Adverse effects of beta blockers
Bronchospasm
Adverse effects of alpha blockers
Widespread side effects
Postural hypotension
How to decide which antihypertensive should be used
Choose ACE inhibitors in diabetes / diabetic nephropathy
- avoid ACE inhibitors in renovascular disease
- choose ACE inhibitors with CHF
- avoid B blockers in asthma
- choose B blockers in ischaemic heart disease
Define infarction
An area of ischaemic necrosis (death of tissue due to lack of oxygen) due to abrupt cessation of the arterial supply or venous draining
- the process of formation of an infarct
Factors affecting development of infarction
Vascular occlusion - from minimal effect to death of patients
Rate of development of occlusion - abrupt Vs gradual
Nature of vascular supply- end artery Vs dual blood supply
Type of tissue: vulnerability to hypoxia (irreversible damage)
Neuron: 2-3mins
Myocardium: 20-40mins
Fibroblasts: many hours
Examples of different infarctions
Myocardial and cerebral infarction: one of the most common cause of death
Pulmonary infarction: variable outcome
Bowel infarction is frequently fatal
Gangrene: life threatening condition
What do the different colours of infarction indicate
Colour is based on amount of haemorrhage
- pale of white infarct: solid organs such as heart and spleen
- red or haemorrhagic infarct: loose spongy tissue rich in blood supply or has due allergies blood supply such as lung
Describe morphology of an infarct
Usually wedge shaped with occluded artery at apex and base at periphery
Margins: early poorly defined slightly haemorrhagic but later well defined
Inflammatory response followed by reparative response - finally scar tissue
Causes of arterial infarction
Occlusion by embolus
Occlusion by atheroma and thrombosis
Occlusion by atheroma with plaque fissure
Occlusion by atheroma alone
Arterial spasm or arterial trauma
Define myocardial infarction
Necrosis of heart muscle due to occlusion of the supplying coronary artery
Outcomes of myocardial infarction
Sudden death due to cardiac dysrhythina or acute left ventricular failure
Rupture of myocardium > haemopericardium
Rupture of papillary muscle > acute valve failure
Survival with infarct replaced by granulation tissue and ultimately fibrous scar
Death due to complications during the infarct healing process
Stages in myocardial infarction
0-12 hours: early stages of cell death
12-24 hours: necrotic muscle fibres apparent microscopically
24-72 hours: acute inflammatory reaction to dead muscle
3-14 days: macrophagic removal of debris and vascular granulation tissue formation
14-21 days : fibrous granulation tissue formation
21-56 days: scar formation and cicatrisation
Late complications of MI
Chronic LVF
Ventricular aneurysm
What is a renal infarct
Usually due to emboli from L side of heart
Wedge shaped
Pale area with hyperaemia around
Heals by scar formation
What is arterial infarction caused by
Atherothrombotic in extra-cerebral arteries
Embolic
What is gangrene
Type of necrosis caused by vascular insufficiency following injury or infection.
Gangrene is a complication of necrosis. Tissue becomes black and malodorous. Bacteria decompose dead tissue- release of hydrogen sulphide and iron -> iron sulphide is black
What is the difference between dry gangrene and wet or moist gangrene
Dry gangrene occurs when the arterial blood supply to an area is occluded but the venous drainage is intact
Wet or moist gangrene is caused by occlusion or impairment of venous drainage plus putrefaction or caused by a bacterial infection
Define gangrene
Localised death and decomposition of body tissue, resulting from obstructed circulation or bacterial infection. Dry, wet / infected and gas (caused by clostridia). Extremities, bowel and internal
What is venous infarction
Can occur when the entire venous drainage from an organ or tissue is, and remains, completely obstructed
2 common examples:
Bowel infarction eg Volvus, hernial strangulation
Testis infarction due to torsion
Ovarian infarction due to torsion
Sequence of events of venous infarction
1) veins become obstructed, usually by extrinsic pressure
2) tissues become congested with blood, venules and capillaries being engorged with blood which cannot escape
3) pressure in capillaries and venules rises so that:
- many of them rupture with leakage of blood
- arterial blood cannot enter so hypoxia ensues
4) tissues become congested, hypoxia and necrotic
What is venous infarction: torsion of testis
Spermatic cord has twisted, thus compressing plexus of veins. Blood cannot drain out of testis or epididymis. Venous infarction occurs
What is LO salt
A KCL salt substitute - advocated for a low salt diet
Has a severe reaction with ACE inhibitors
Can cause hyperkalaemia so would worsen ACE inhibitor induced hyperkalaemia
What is alteplase
Clot busting drug. Activates plasminogen to form plasmin (an enzyme that breaks down fibrin to break up a clot)
Describe blood flow to the renal system
25% of cardiac output goes to kidneys
Renin secreting cells have a sympathetic innervation
Local: good autoregulation of flow over a wide pressure range
Hormones: noradrenaline, adrenaline, angiotensin can cause constriction. Vasopressin may cause vasodilation via prostaglandin / NO release. Dopamine causes vasodilation
What are the special features of renal blood flow
Excretory function of the kidney depends on well maintained flow. Vascular connections provide for capacity to regulate afferent / efferent resistances
What do centrally acting antihypertensives do eg alpha-methyl dopa, moxonidine
Decrease sympathetic output from central cardiovascular control centres in the medulla
- alpha -methyl dopa is a false substrate resulting in an analogue of noradrenaline acting at central a2-adrenoceptors
- moxonidine: an imidazoline which activates central imidazoline receptors
These agents are not widely used due to widespread side effects and no advantages over other antihypertensive agents
Factors affecting the development of infarction
Vascular occlusion - minimal effect to death of patients
- nature of vascular supply: end artery Vs dual blood supply
- rate of development of occlusion: abrupt Vs gradual
- type of tissue: vulnerability to hypoxia (irreversible damage)
