Hypertension pharmacology Flashcards
3 key factors determining blood movement
Flow - determined by change in pressure and resistance to flow
Pressure - generated by heart
Reisstance
How to calculate flow
Change in P / R
What does resistance depend on?
- Blood viscocity: thicker the blood, higher resistance to flow, e.g. increase in count (haematocrit), LDL - cholesterol or dehydrated
- Vessel length (L): longer the vessel, higher the resistance to flow. Unlikely to change in adult
- Vessel radius (r): narrow vessel = higher resistance to flow. Most important variable
How to calculate resistance
(viscosity x length) / (radius ^ 4)
What does cardiovascular system do?
Delivers oxygen and nutrients
Distributes hormones, fluids, electrolytes
Immune system
Thermoregulation
Characteristics of the pulmonary circuit
Relatively short, simple and operates at lower pressure than systemic
Where is blood regulation specialised?
Coronary, skeletal muscle, skin, cerebral, renal, GI, hepatic
What is the portal system?
From one capillary bed to another without passing through the heart
Why does pulmonary circuit have lower resistance?
Lower pressure too, fewer small vessels
Cardiac output, pulmonary vs systemic
Equal
Resistance, pulmonary vs systemic
Pulmonary is lower
Pressure in pulmonary vs systemic
Pulmonary is lower
How to diagnose hypertension
- Measure BP in both arms - if the difference is more than 15mmHg repeat measurements
- If difference remains higher, measure BPs in arm with higher reading
- If BP is 140/90 mmHg or higher, take second measurement, if this is v
- If BP is between 140/90 and 180/120 offer BP monitoring to confirm hypertension
- Whilst waiting, carry out investigations for target organ damage and assessment of cardiovascular risk
- When using ABPM to confirm hypertension ensure 2 measurements are taken per hour
- When using HBPM to confirm hypertension, ensure that for each BP recording, 2 consecutive measurements are taken, at least 1 minute apart with the person seated, BP is recorded twice daily (morning and evening) and BP monitoring continues for 4 days
- Confirm diagnosis with clinic BP of 140/90 or higher and ABPM daytime average or HBPM average of 135/85 or higher
- If hypertension not diagnosed, measure BP every 5 years and measure more frequently if clinic BP is close to 140/90
What is the dicrotic notch?
After blood forced into aorta, increasing pressure closes aortic valve and increase pressure
What re the capacitance vessels?
Veins
How to calculate mean arterial blood pressure
Cardiac output x total peripheral resistance
Neurological regulation of BP
- Autonomic NS
- Short-term regulation
- Influences cardiac output and vascular resistance
- Signals to SAN
Humoral regulation of BO
- Aldosterone, adrenaline, ADH, atrial natriuretic peptide, angiotensin ii
- Short and long term regulation
- Influences vascular resistance and blood volume
Arterial baroreceptors
- Located in aortic arch and carotid sinus
- Mechanoreceptors - stretch in wall
- Aortic depressor nerve is branch of vagus nerve
- Monitor arterial BP
- Input to cardiovascular centre in medulla oblongata
- Output is autonomic nervous system response
- Rapid, short-term control of BP
- Continually send nerve impulses to cardiovascular centre in medulla
- Frequency at which they fire nerve impulses to CV centre is dependent on arterial BP
- Always firing - always muscle tone
How do baroreceptors regulate BP?
- Rapid response to short-term changes in MABP
- Arterial baroreceptors sense changes in MABP according to stretch of artery walls in aortic arch and carotid sinus
- Firing rate of APs along afferent glossopharyngeal and vagus nerves increases or decreases relative to arterial wall stretch
- Sensory information received by medullary cardiovascular centre in medulla oblongata
- Afferent AP frequency into CV centre from baroreceptors determines rate at which APs are sent along efferent neural pathways
- Vagus nerve (parasympathetic, efferent) neurons to heart - altered heart rate and consequent CO, increases PS output to SAN
- No parasympathetic to vascular smooth muscle
- Sympathetic neurons to heart, arterioles and veins - altered HR, CO and vasoconstriction/dilation,
- A1 interaction = vasodilation (SVR decreases) = vascular smooth muscle, sympathetic
- Decrease B1 receptors = reduced CO
- Carotid through glossopharyngeal
What does aldosterone do?
released from adrenal cortex in response to decreased blood volume, increases Na+ and water reabsorption from kidneys = higher BP
What does ADH do?§
released from posterior pituitary in response to increased blood osmolality, increases water reabsorption from kidneys and vasoconstriction, short term effector = higher BP
What does RAAS do?
long term response to decreased body fluid volume, loss of both water and salt resulting in no change in osmolality
What do type A and B natriuretic peptides do?
released in response to high volume load (stretch) on atria and ventricles, increases water and Na+ excreted from kidneys = decreased BP
What does adrenaline do?
released from adrenal medulla in response to sympathetic nerve simulation (fight or flight response), actions on vascular smooth muscle depends on adrenergic receptors
Examples of A1 receptors and what they do
GPCRs - G-alpha-Q, IP3, DAG, PKC increase Ca2+ in smooth muscle - vasoconstriction
What do B2 receptors do and example
GPCRS - G-alpha-S, adenylate cyclase, cAMP
Where does adrenaline normally act when does this change?
Normally B2 but when delivered in high amounts can do A1
Characteristics of A1
Vasoconstriction
Higher density in body
++ adrenaline
+++ nor-adrenaline
Characteristics of B2
Vasodilation
Higher density in skeletal and cardiac muscle
+++ adrenaline
+ nor adrenaline
What does angiotensin ii do?
Vasoconstructor activated by angiotensin converting enzyme (ACE) within blood vessels
Three layers of blood vessels and characteristics
- Tunica intima/interna: innermost, endothelial cells, basement membrane, connective tissue
- Tunica media: middle, internal and external elastic lamina, smooth muscle cells, elastin and collagen
- Tunica externa/adventitia: outer, connective tissue, nerves, blood vessels, collagen and elastin, has sympathetic nerves for contraction
What is the vast vasorum?
large nerves have own blood vessels in adventitia
Variation between arteries, arterioles and veins
- Arteries: thick elastic/muscular walls that release distention and maintain high pressure
- Arterioles have thicker walls relative to lumen = good constrictors
- Veins have thin walls and large, distensible lumens - good for holding blood = capacitance
Characteristics of large elastic arteries
Buffer pressure change, convert intermittent to continuous flow and maintain pressure
Thick media = lots of elastin for rebound
Wide lumen
Low resistance but high pressure
Characteristics of muscular arteries
- Also called distributing or peripheral arteries
- Distribute flow, resist collapse at joints and adjust blood flow to joints/organs
- Thick smooth muscle media with less elastic fibres
- Smooth muscle allows some degree of vasoconstriction/dilation to adjust flow
- Thick tunica externa with loose structure and longitudinal collagen fibres prevents retraction when cut
- Range from 1 cm to 0.5 mm
- Distribution arteries - more smooth muscle but low resistance conduits and not able to generate MABP
Characteristics of arterioles
- Main site of resistance - lots of small vessels
- Walls contain thick layer of smooth muscle
- Lots of sympathetic nerve endings - vasoconstriction (a1) or vasodilation (b2)
- Arteriolar vasoconstriction increases upstream arterial BP but reduces downstream flow to tissues
- Active hyperaemia - adjust blood flow to tissues according to metabolic demand
Characteristics of capillaries
- Nutrients and gases are exchanged between blood and tissue fluids
- 4-10 micrometre in diameter
- Branched and extensive network
- Large cross-sectional area
- Thin walled - endothelial cell and basement membrane
- More abundant in metabolically active tissue
- Only about 25% perfused at rest due to presence of precapillary sphincters and metarterioles
- Nailfold capillaries - single file flow at low velocity, RBCs have to deform to fit
What are continuous capillaries?
muscle, skin, lung, fat, nerves
What are fenestrated capillaries?
Fluid exchange, renal glomerulus, synovial
Discontinuous/sinusoid capillaries
Spleen, liver, gaps allow RBC into bone marrow
How to calculate velocity?
Blood Flow / cross sectional area
What is hydrostatic pressure?
Flow and vessel resistance (BP), pushes water out of vessels
What is osmotic pressure?
Colloid and oncotic pressure, determined by charged proteins that pull water into vessels
Veins and venules
- Venules communicate with arterioles to match capillary inflows and outflow
- Veins have valves - permits one way flow back to the heart
- Act as capacitance vessels - 65% of blood volume
- Thin walled, large lumens
- Skeletal muscle pump and respiratory pump aid venous return from lower body
- Venoconstriction (a1) shunts blood from peripheral to central vessels to increase stroke volume (exercise)
- Release of norepinephrine from sympathetic neurones induces venoconstriction increases blood flow into right atrium
What can hypertension cause?
Stroke (ischaemic and haemorrhage) Left ventricular hypertrophy Heart failure Angina Organ damage
Why are people hypertensive?
Stress - work, diet, fam history etc
Essential hypertension
Obesity - 95% of cases
Secondary hypertension
- Young, difficult to treat
- Rapid onset
- Abnormal biochemistry
- Abnormal urine dip
- Headache/neuro
- Abdominal pain
Treatments for hypertension
- Lifestyle factors very important
- Weight loss
- Low salt diet
- Exercise
- Smoking
- Alcohol
- For T2D recommend ARB/ACE inhibitor, under 55
- Over 55 or BAME = calcium channel blocker
What does amlodipine do?
- Blocks L-type voltage gated calcium channels
- Vasodilation in vascular tissue
- Smooth muscle vasodilates due to blockers
What do calcium channels do?
Dilate channels to increase radius
How to calculate SV
Preload, afterload and contractility
How to determine preload
venous blood volume and vascular compliance and ventricular compliance
How to determine afterload
arterial resistance, arterial compliance and wall stress
What do diuretics do?
ACEI and ARBs - reduce preload
What do CCB, ACEI and ARBs do?
Reduce afterload
What is spirolactone?
Weak antagonist of androgen receptor - males may exhibit gynaecomastia
Angiotensin ii and renin
- Angiotensin ii impacts arterial resistance
- Renin production stimulated by reduced stretch in juxtoglomerular apparatus = causes renin production
- Renin constricts blood vessels and retains sodium and water
- For drug to reduce action of RAAS system, it should inhibit angiotensin converting enzymes
- ACE inhibitors - angiotensin converting enzyme inhibitors - enalapril
- ACE breaks down bradykinin
- ACE inhibitors end in -pril
- Bradykinin correlated with cough and angioedema. Side effects of ACE include cough and angioedema
- RAAS blockade also targets AT1 angiotensin ii receptors
- Angiotensin ii receptor blockers cause no increase in bradykinin
- When aldosterone impaired, serum potassium will rise
- Aldosterone holds onto sodium in exchange for potassium
