phys pharm - Circulation & Peripheral CV Flashcards
Function of vascular system:
to supply oxygenated blood and nutrients to tissues and remove waste products
Circulation:
Consists of a pump (heart) and tubes (the vessels and capillaries)
Blood flow to each tissue is regulated by local chemical and general neuronal and humoral mechanisms
Blood vessels have 3 layers:
- connective tissue adventitia
- smooth muscle layer
- endothelium
Capillaries:
Capillaries made from endothelial cells (single cell thick)
oxygen and nutrients enter the interstitial fluid and carbon dioxide and waste products enter the bloodstream
transport across capillaries:
- diffusion of lipid soluble substances through plasma membranes
- diffusion of lipid insoluble substances through endothelial pores
- bulk flow of water and dissolved substances
- exocytosis / endocytosis
the blood brain barrier:
Acidic dyes e.g. trypan blue injected into bloodstream all tissues except brain and spinal cord were stained.
Barrier is the endothelium of the cerebral capillaries and the choroids plexus epithelium
Only water, CO2 and O2 enter the brain with ease with the exchange of other substances between blood and brain is slow.
Helps to maintain a constant environment around the neurons.
Lymphatics:
Lymphatics drain into subclavian and jugular veins
Lymphatics act as a filter at the lymph nodes (packed with lymphocytes and phagocytes) and remove foreign particles such as bacteria
= an important component of body’s defences.
Oedema =
block of lymph flow, so protein from capillaries builds up in interstitial spaces, and promotes water retention
- may result from injury, inflamation, parasitic infection or surgery.
Blood pressure:
systolic – force of the heart
diastolic – basal BP in the system
normal young adult at rest 120 systolic /70 mm Hg diastolic
rises slowly with age and with 50-70 yr. old expected 130/80
hypertension:
high blood pressure
diastolic arterial BP > 90 mmHg
increased risk of other diseases, e.g. heart attack and stroke
primary hypertension = no apparent cause but associated with genetics, obesity, alcohol, lack of exercise and smoking
secondary hypertension = caused by renovascular disease or endocrine disease (e.g. tumour of adrenal - secretes excessive adrenaline)
factors regulating blood pressure:
1) Changes in cardiac output
2) Peripheral mechanisms involved in control of blood flow
Main classes of regulation (non-cardiac)…
1) Drugs that affect the sympathetic nervous system/muscle contraction
2) Endothelium/local regulation
3) The renin-angiotensin system
4) Changes in blood volume
Neuronal control of blood pressure:
Detection of blood pressure by baroreceptors in aortic arch and carotid sinus
=Increase in pressure = increases in baroreceptor output
Changes in baroreceptor activity produce RECIPROCAL changes sympathetic activity
Increased baroreceptor activity – decreased sympathetic activity
Decreased baroreceptor activity – increased sympathetic activity
3 sites of action to block artery contraction:
(i) block NA release from sympathetic nerve varicosities
(ii) adrenoceptor antagonists that act on α1-adrenoceptor (Gαq) receptors
(iii) effects on calcium = no contraction
Adrenergic neuron blockers: Reserpine…
Reserpine an alkaloid extract of the roots of a climbing shrub
Reserpine is taken into nerve by uptake 1 and binds to storage
vesicles and stops them concentrating NA so less NA for release
Adrenergic neuron blockers: Guanethidine…
anti-hypertensive
Mechanism of action – taken up by uptake 1, competes with NA to be taken up into storage vesicles (higher affinity at pump than NA) – so decrease in NA stored
can also block action potential propagation
Adrenergic neuron blockers side effects =
hypotension
depression
α1-adrenoceptors agonists…
treatment of hypotension and shock (caused by hypovolemia)
e.g. methoxamine and phenylephrine - lead to an increase in BP through activation of smooth muscle α1-adrenoceptors
α1-adrenoceptors antagonists…
treatment of hypertension
e.g. prazosin - blocks noradrenaline induced artery constriction
α2-adrenoceptors agonists…
act pre-synaptically to inhibit transmitter release
e.g. clonidine and methyldopa
α2-adrenoceptors antagonists…
e.g. yohimbine - blocks prejunctional α2-adrenoceptors and so will potentiate transmitter release from sympathetic nerves.
Calcium and artery contraction:
- sympathetic nerve stimulation leads to depolarisation of smooth muscle and activation of voltage dependent calcium channels
- α-adrenoceptor activation couples through Gq to stimulate PLC-β and generate IP3 which releases calcium from calcium stores
- calcium reacts with calmodulin = stimulation of myosin light chain kinase = phosphorylates myosin = contraction
Calcium channel antagonists act on different voltage dependent calcium channels…
:
N-type – act on Neurons involved with transmitter release
T-type – act in brain and heart, Transient opening
L-type – act on smooth muscle, Long lasting
Role of the endothelium:
endothelium is also able to exert control over the vascular system by the production of vasoactive substances
e.g.
vasoconstrictors (endothelins)
or
vasodilators
nitrovasodilators =
mostly used in treatment of heart failure
e.g. Sodium nitroprusside is given to reduce BP during hypertensive emergency = breaks down to produce NO inside smooth muscle cells
Role of the kidney in controlling blood pressure:
Rein-angiotensin system
Regulation of blood volume
Actions of Angiotensin II…
Vasoconstriction
Increase in blood pressure
Aldosterone release from adrenal cortex = Na+ and water retention = Release of vasopressin ADH = increases fluid retention in kidney
Stimulates thirst centre in brain
Facilities norepinephrine release = stimulates cardiac hypertrophy
Diuretics:
= drugs that increase the rate of urine flow
- increase the rate of excretion of salt, increased water loss
- decrease the reabsorption of sodium and chloride from the filtrate
- reduce the volume of extracellular fluid by decreasing total body NaCl content
Kidney Function:
- excretion of waste products such as urea
- regulation of salt, electrolytes and volume of extracellular fluid
2 functional parts of the nephron of the kidney…
- filtering apparatus (the glomerulus)
- tubular portion that reabsorbs from the filtrate
different type of diuretics:
- loop diuretics (Na+, Cl- out)
- early distal tube diuretics (Na+ out)
- potassium sparing diuretics (Na+ out, K+ in)
- osmotic diuretics
Regulation of volume and blood pressure: loop diuretics…
e.g. frusemide
cause 15-25% of the sodium in the filtrate to be excreted
inhhibit transport of NaCl out of tubule
Regulation of volume and blood pressure: early distal tube diuretics…
e.g. bendrofluazide
drugs acting on the distal convoluted tubule
inhibit Na+/Cl- co-transporter
treats hypertension
Regulation of volume and blood pressure: Potassium sparing diuretics…
e.g. amiloride
Block excretion of potassium into urine
treat hypokalemia (low potassium leading to tachycardia)
Regulation of volume and blood pressure: Osmotic diuretics…
e.g. mannitol
are incompletely reabsorbed, and increases osmolarity in the tubule
= increase amount of water excreted
