Cardiovascular Physiology Flashcards
What are the tissue layers in the vascular system?
Adventitia - connective tissue
Smooth muscle
Endothelium
What are the tissue properties of arteries?
Thick elastic tissue layer
Some smooth muscle
Endothelium
What are the tissue properties of arterioles?
Less elastic tissue than arteries
More smooth muscle than arteries
Endothelium
What are the tissue properties of capillaries?
One cell thick endothelium
What are the tissue properties of veins?
Little smooth muscle
Walls slightly thicker than capillaries
Large lumen
How is blood transport carried out in capillaries.
Connect arterioles to venules.
Dilate to the diameter of 1 red blood cell.
Nutrients enter interstitial fluid.
Waste enters capillary.
How do different substances cross the capillary wall?
Lipid soluble molecules fuse with the plasma membrane
Lipid-insoluble molecules travel through endothelial pores
Large molecules endo/exocytose through the plasma membranes
Which part of the vascular system is impermeable to most substances?
Blood-brain barrier?
Where is the blood-brain barrier located?
Endothelium of cerebral capillaries and epithelium of choroid plexus.
How can the impermeability of the blood-brain barrier be shown experimentally?
Using tryptan blue dye. The brain/spinal cord will be the only part of the vascular system not affected by the dye.
Which substances can permeate the blood-brain barrier?
CO2
O2
What is the function of the blood-brain barrier?
Maintaining a constant extracellular environment around neurones.
How are fluids exchanged between capillaries and lymphatics?
Interstitial fluid drains into the lymphatic system.
Periodic swelling of lymph nodes.
Valves open when swelling too high.
Lymph drains into subclavian/jugular veins.
Lymph removes bacteria via lymphocytes.
What effect does oedema have on the lymphatic system and the body?
Blocks lymph flow by a build up of protein from capillaries in interstitial spaces.
Promotes water retention.
Causes injury, inflammation, and infection.
What function do valves perform in veins and lymphatic system?
Ensure single direction of flow.
What could cause reversed flow of blood?
Muscle contraction
Valve tissue damage
What is systolic blood pressure?
Pressure caused by force of the heart
What is diastolic blood pressure?
Basal blood pressure in the system
What is a normal blood pressure reading for a healthy adult?
120/70
What are the units for measuring blood pressure?
Millimeters of Mercury (mm Hg)
What happens to blood pressure with age?
Rises slowly to 130/80
Describe how blood pressure is measured and the changes in bloodflow that occur during measurement.
Cuff is inflated to >120mm Hg - Stops arterial blood flow.
Cuff slowly deflates. 120-80mm Hg - Blood starts to surge in korotkaft sounds.
Cuff deflated to <80mm Hg - silent bloodflow.
What is cardiac Output?
Blood flow at any level of circulation.
How is flow calculated?
Pressure/Resistance
How is the relationship between vessel and resistance?
Resistance proportional to 1/r^4 where r is the radius of the lumen.
How is blood velocity calculated?
Flow rate/cross sectional area of vessel.
How is hypertension defined?
Diastolic blood pressure exceeding 90mm Hg.
What are the possible effects of hypertension?
Heart attack
Stroke (myocardial infarction)
What is primary hypertension? What are the associated risk factors?
Hypertension with no apparent cause. Risk factors include alcohol, obesity and genetic predisposition.
What can secondary hypertension caused by?
Renovascular disease
Endocrine disease
Adrenal tumour
How does an adrenal tumour induce hypertension?
Causes excessive adrenaline secretion.
What are the factors regulating blood pressure?
Changes in cardiac output
Peripheral control of blood flow
Drugs acting on sympathetic NS or muscle contraction
Endothelium regulation
Renin angiotensin system
Changes in blood volume
How is blood pressure detected in the body?
Baroreceptors.
Where are baroreceptors located?
Aortic arch
Carotid sinus
What effect would an increase in pressure have on baroreceptors?
Increase in baroreceptor output.
What effect to baroreceptors have on the sympathetic nervous system?
Increased baroreceptor output causes decreased sympathetic activity and vice versa.
Describe the pathway by which baroreceptors affect sympathetic activity.
Input from baroreceptor leads into the brain.
Signal relayed onto sympathetic system in the vasimotor centre via an inhibitory neuron.
Sympathetic nerve contains a sympathetic ganglion. Relays the signal onto the artery.
How do sympathetic neurons relay the signal onto arteries?
Via depolarisation-stimulated NA release from varicosities. NA activates GqPCRs on the artery. Causes formation of IP3 that leads to muscle contraction.
What are the 3 ways via which arterial contraction can be blocked?
NA release
Adrenoceptor antagonists
Effects on calcium (secondary messenger pathway)
Give 2 examples of adrenergic neuron blockers that can be used to inhibit arterial contraction.
Reserpine
Guanethidine
How does reserpine affect arterial contraction?
Taken up into axon via uptake 1
Affects storage of NA
Binds to NA vesicles and stops them concentrating NA
Decreases amount of NA stored
What are the side effects associated with reserpine use?
Depression
Peripheral (non-CNS) action
How does guanethidine affect arterial contraction?
Taken up into axon via uptake 1
Competes with NA for storage in vesicles - has higher affinity at the pump than noradrenaline
Decreases amount of NA stored
Also blocks AP propagation.
Why is guanethidine effective as a false substrate?
Has higher affinity at the vesicle pump than NA.
What is a common side effect of adrenergic neuron blockers?
Postural hypertension
What is postural hypertension?
Bloods falls down upon standing up. Muscles don’t contract in time to stop this.
Where in the cardiovascular system are Alpha1-adrenoceptors located?
Artery Smooth muscle
What causes cardiovascular shock?
Inadequate perfusion with blood caused by hypovolemia or cardiac failure.
What is hypovolemia?
Loss of blood volume due to dehydration or blood loss.
Give examples of pharmaceuticals that can be used to treat cardiovascular shock.
Alpha1-adrenoceptor agonists:
Methoxamine
Phenylephrine
How do Alpha1-adrenoceptor agonists work to treat cardiovascular shock?
Increase BP through activation of smooth muscle via alpha1-adrenoceptors.
What type of pharmaceutical can be used to treat hypertension? Give an example.
Alpha1-adrenoceptor antagonists e.g.: Prazosin
How do Alpha1-adrenoceptor antagonists work to treat hypertension?
Blocks NA-induced vasoconstriction
Where in the cardiovascular system are the Alpha2-adrenoceptors present?
Nerve terminals
What effect do Alpha2 agonists have on neurones? Outline central and peripheral effects.
Inhibit NT release presynaptically
Central (vasimotor centre) - Decreases sympathetic output
Peripheral (artery) - Decreases NA release from varicosities
Give an example of an alpha2 antagonist and it’s effect on the cardiovascular system.
Yohimbine.
Blocks presynaptic alpha2-adrenoceptors.
Promotes NT release from terminals
Describe the mechanism of calcium induced artery contraction.
Rise in intracellular calcium.
Calcium binds to calmodulin which forms a complex.
Complex stimulates MAPK to phosphorylate myosin.
Phosphorylation causes contraction.
By which receptor pathway does arterial contraction occur?
Activation of GqPCRs.
Where are N-type calcium channels located an what is their function?
On neurones
Involved in depolarisation/NT release
Where are T-type calcium channels located an what are their properties?
Heart and brain
Transient-opening channels
Where are L-type calcium channels located an what are their properties?
On smooth muscle
Long-lasting opening
Which molecules can be used as L-type channel blockers? Give examples.
Dihydropyridines (DHPs) e.g.: Nifedipine
Phenethylalkalmines e.g.: Verapamil
Benzotiazepines e.g.: Diltiazem
Which DHP acts as an L-type channel opener rather than a blocker?
BayK8644
Describe the 3 modes of L-type channel opening.
Mode 0 - Cannot open on depolarisation
Mode 1 - Low probability of opening on depolarisation
Mode 2 - High probability of opening on depolarisation
What is the effect of BayK8644 on opening of L-type calcium channels compared to Nifedipine?
BayK8644 increases calcium currents causing the opening to change from mode 1 to mode 2. Nifedipine changes the mode of opening from 1 to 0.
What are the common side effects of using DHPs?
Headache
Heart palpitations
Sweating
Flushing
Effect on other smooth muscle
What is the site of action of Nifedipine?
L-type calcium channels of the smooth muscle.
What is the site of action of Verapamil?
L-type calcium channels of the heart.
What is the site of action of Diltiazem?
L-type calcium channels of the smooth muscle and the heart.
What are endothelins?
Vasoconstrictors produced in endothelium.
How are ET-1 endothelins produced?
Produced at level of transcription.
Precursor “Pre-proET” processed.
Forms big WT-1. Cleaved by endothelin converting enzyme.
Forms ET-1.
Where are ET-1 located?
Endothelial cells of various tissues.
Where are ET-2 located?
Kidney.
Where are ET-3 located?
Brain
Lung
Adrenal gland
What are the 2 types of endothelin receptors?
ETA
ETB
What effect does activation of ETA receptors have on the body?
Causes vasoconstriction via GqPCR pathway
What is the function of endothelins?
Paracrine (local) or autocrine vasoconstrictors
May play a role in pregnancy
Which vasodilators may revert the effect of endothelins?
Prostacyclin
Endothelium derived relaxing factors (EDRF)Nitrovasodilators
How do EDRFs work?
Nitric oxide biosynthesis by the synthase enzyme (NOS) in endothelium.
NO diffuses into smooth muscle.NO stimulates guanylate cyclase.
Promotes production of cGMP.
cGMP stimulates PKG which causes relaxation.
How is NOS activity controlled?
NOS activity controlled by calcium/calmodulin. Rise in Ca-calmodulin activates NOS.
What are nitrovasodilators used to treat? Give examples.
Heart failure.
Sodium nitroprusside.
How does sodium nitroprusside work to treat heart failure?
Reduces blood pressure by breaking down into NO in the smooth muscle. NO causes muscle relaxation which lowers the blood pressure.
What is renin?
An enzyme that catalyses conversion of angiotensinogen to angiotensin in the plasma.
Where is renin synthesised stored and secreted?
Granular juxtaglomerular cells of the kidneys.
What is angiotensin?
Vasoactive substance used in control of blood volume by the renin-angiotensin system.
How are angiotensin I and II different?
Angiotensin II can be synthesised from I by cleaving 2aa off the C-terminal in angiotensin I. Cleaving catalysed by angiotensin converting enzyme.
What inhibits conversion of angiotensin I to angiotensin II? Give an example
ACE inhibitors
e.g.: Captopril
What are the two types of angiotensin II receptors?
AT1
AT2
What type of receptors are AT1 and AT2?
GPCRs
Where are AT1 receptors located?
Vascular tissue
Myocardial tissue
Where are AT2 receptors located?
Adrenal medullaCNS
What pathway does activation of AT1 lead to?
GqPCR pathway involving PLC-beta. Leads to contraction.
Give an example of an AT1 receptor antagonist.
Losatran
How does the renin-angiotensin system regulate blood volume?
Decrease in NaCl in the filtrate is sensed by macula densa cells of the distal tubule.
Stimulates renin release, via activation of beta-adrenoceptors, which is inversely proportional to the local blood pressure.
What are Diuretics?
Drugs which increase rate urine flow.
How do diuretics increase the rate of urin flow?
Some increase rate of excretion of sodium.Most reduce the volume of extracellular fluid by decreasing total body NaCl.
Why does decreasing body NaCl reduce the extracellular fluid volume?
NaCl is the major determinant of extracellular fluid volume.
What is the primary effect of diuretics?
Decrease in reabsorption of sodium and chloride.
What is the secondary effect of diuretics?
Increase in water loss.
What is the main filtering apparatus of the kidney?
The glomerulus of the nephron.
What is the function of the tubular portion of the kidney?
Reabsorption of substances from the filtrate.
How is the composition of filtrate different to the composition of blood plasma and why?
Filtrate lacks protein which can’t pass through the basement membrane of the glomerulus.
Give an example of a diuretic that acts on the loop of Henle.
Frusemide.
How does Frusemide perform its function in the kidney?
Causes 15-25% of sodium in the filtrate to be excreted.
Inhibits Na/-K/-Cl symporter which prevents reabsorption of NaCl in the ascending limb.
Indirect vasodilation by release of renal factor.
What can loss of potassium cause?
Hypokalemia. Affects cardiac function.
Give an example of a diuretic that acts on the distal tubule.
Bendrofluazide.
How does Bendrofluazide perform its function in the kidney?
Inhibits the Na/Cl cotransporter.
Why are DCT diuretics less effective than those affecting the loop of Henle?
90% of the filtrate is reabsorbed before it reaches DCT.
How can DCT diuretics be used to treat hypertension?
Decrease BP due to decrease in blood volume.
Act indirectly on blood vessels to stimulate further BP drop.
Give an example of a potassium sparing diuretic.
Amiloride.
How does Amiloride perform its function in the kidney?
Block potassium excretion.
How What are the benefits and issues with using Amiloride as a diuretic?
Unlike Frusemide it prevents hypokalemia however may cause cardiac disorders such as tachycardia.
What is tachycardia and how may Amiloride cause it?
Abnormally high heart rate.
Caused by high potassium to sodium ratio in cardiac axons.
Causes more rapid repolarisation of neurons.
Lowers ventricular fibrillation which disrupts coordination of cardiac muscles.
Give an example of an osmotic diuretic.
Mannitol.
How does Mannitol perform it’s function in the kidney?
Mannitol increases the osmolarity of filtrate causing less water to be reabsorbed.
What are the common combination treatments in diuresis?
Beta-antagonist + diuretic.
ACE inhibitor + diuretic.
