Blood and Circulation Flashcards
What makes up total body water?
Intracellular fluid (ICF) + Extracellular fluid (ECF)
What does extracellular fluid consist of?
Plasma, interstitial fluid, transcellular fluid (cerebrospinal, synovial, intraocular fluids).
What is the average TBW for a man and a woman?
In a typical man TBW = 60%
In a typical woman TBW = 52% (because fat contains a low amount of water)
What are the 2 differences between the concentration of solutes in interstitial fluid and plasma?
1) The protein concentration in interstitial fluid is very low compared to the plasma.
2) Half the calcium in plasma is protein bound, which means that the total calcium concentration in the interstitial fluid reduces correspondingly as there is already low protein concentration in the interstitial fluid.
Explain what the dilution principle is
Add a known amount of solute to an unknown volume of a liquid.
Can then find the concentration of the solution.
Volume = amount ÷ concentration
(m/c x v)
How can the dilution principle be used to find the volume of different body fluid compartments?
Add a specific solute into the body, and find the concentration of that body compartment.
From this the volume of the body compartment can be calculated.
However because different body compartments have different properties, solutes that look different in different body compartments are used.
What solute is used to find total body water volume?
Tritiated water
3H2O
What solute is used to find extracellular fluid volume?
Inulin
What solute is used to find plasma volume?
Evans blue, 125 I albumin, must stay in vascular system.
Plasma proteins are labelled isotopically.
How can the intracellular volume be calculated?
Calculated by finding the difference between the total body water and the extracellular fluid.
How can the interstitial fluid volume be calculated?
Calculated by finding the difference between the extracellular fluid and plasma.
What factors have to be considered when finding the volume of body compartments in vivo?
1) Have to consider the equilibrium time for a given substance.
3H2O and inulin need time to distribute between the compartments.
2) 3H2O can be lost in urine and sweat.
3) Inulin is filtered by the kidney so will also be lost in urine.
4) Evans blue has a short half life of 10-30 mins so any measurements need to be taken quickly.
Why is transcellular fluid volume usually discounted?
It is relatively small
Define osmotic pressure
Pressure sufficient enough to prevent movement of water into a solution across a partially permeable membrane.
Has a low water potential so will attract water towards it.
It opposes hydrostatic pressure.
Define osmolarity
Number of moles of a solute per litre of water.
Define osmolality
Number of moles of a solute per kilogram of water. In a solution it would be the number of osmoles of solute per kilogram of solvent.
Units are the osmole.
How do you calculate the osmolality of solutions that dissociate in water?
Solutions that dissociate have 2 ions in the solution so the osmolality will double.
Outline the changes in osmolality when glucose is moved into the intracellular fluid?
When glucose moves into the intracellular fluid there will be more solute in this fluid. This therefore means the osmolality of the intracellular fluid will increase. Water moves from a low to high osmolality, so water will move into the intracellular fluid by osmosis.
What is the definition of total osmolality and and example of this?
Total osmolality = sum of osmolality due to each of the constituents of the solution.
An example of this is the plasma. Its osmolality is around 295 mOsmolkg-1.
How much do ions contribute to the osmolality of plasma?
Na+, Cl-, HCO3- contribute ot most of this.
Glucose and other small molecules contribute less than 10 mOsmolkg-1.
Plasma proteins contribute only 1 mOsmolkg-1.
What will happen if the osmolality of the plasma is increased?
Water moves from a low to high osmolality, so water will move into the plasma from other parts of the body.
What is the osmotic gradient if an RBC is placed in a hypotonic solution?
A hypotonic solution will have a low osmolality (less solute).
Water moves from a low to high osmolality. This means that water will move from the solution and into the RBC.
This will cause the RBC to burst by haemolysis.
What is the osmotic gradient if an RBC is placed in a hypertonic solution?
A hypertonic solution has a high osmolality (more solute). Water moves from a low to high osmolality. This means water will move from the RBC and into the solution. This will cause the RBC to undergo crenation.
Define tonicity
Tonicity is the influence of the osmolality of a solution on the volume of cells.
Define iso-osmotic
Two solutions with the same osmolality as each other.
Define isotonic
Two solutions with the same concentration of solute as each other, so there is no concentration gradient.
This can only occur if the solutes cannot cross the cell membrane.
What is a rule about isotonic and iso-osmotic solutions?
All fluids that are isotonic are also iso-osmotic (if they are the same concentration they have to be iso-osmotic).
BUT not all iso-osmotic solutions are isotonic with cells -> May have the same concentration of solute however in cells movement of water depends on the salt concentration of the blood, which may not be iso-osmotic with the solution even if it is isotonic.
What is an effective osmole?
When a solution is isotonic with the surrounding solution, and the solute cannot pass across the cell membrane. Means there is no net water movement.
What is an ineffective osmole?
When a solute is permeating and can pass across the cell membrane, so the solution cannot be isotonic with the surrounding solution.
Means there will be movement of water either in or out of the cell.
How is the rapid ingestion of 1L of water distributed in different body compartments?
ECF = 1/3 of TBW
ICF = 2/3 of TBW
Plasma = 20% of ECF
According to this each body compartment will increase by that specific volume.
How is the rapid ingestion of 1L of 0.9% saline solution distributed in different body compartments?
0.9% saline solution is around 300 mOsmoles, which is iso-osmotic to plasma. Means solutes pass cross the membrane.
However there are no ATPase pumps on cell membranes so Na+ ions cannot pass into the intracellular fluid. It is an effective osmole.
Means the saline solution is distributed only within the extracellular fluid.
The saline solution is iso-osmotic with the plasma and isotonic with ICF.
How is the rapid ingestion of 1L of 5% albumin distributed in different body compartments?
Albumin is a blood protein, so cannot pass across the cell membrane of blood vessels by diffusion. It is an effective osmole.
This means the albumin stays within the plasma only.
What are the 4 different pressures (Starling’s forces) that control the movement of fluid across capillary membranes?
Hydrostastic pressure from arteriole end of capillary = Pressure from the heart that forces fluid out of the capillary. It is highest in arteriole end and lower in the venue end due to loss of fluid.
Interstitial fluid hydrostatic pressure = Pressure from the fluid outside the capillary that forces fluid into the capillary.
Plasma colloid oncotic pressure = Osmotic pressure from the colloids in the capillary that pulls water into the capillary. The colloids cannot pass across the membrane.
Interstitial fluid colloid osmotic pressure = Osmotic pressure from the colloid in the interstitial fluid that pulls water out of the capillary. Lower than plasma oncotic pressure are there are less proteins here.
What is unique about the oncotic pressure gradient?
It remains the same as the protein concentration is always constant.
What is the process that occurs when the outwards forces from capillary exceed the inward forces?
Filtration
What is the process that occurs when the inward forces from the capillary exceed outward forces?
Reabsorption
Describe the tissue pressure balance in the normal capillary
In the arteriole side filtration takes place as hydrostatic > oncotic pressure.
In the venous side reabsorption takes places as oncotic > hydrostatic pressure.
The level of filtration and reabsorption is almost identical.
Describe the tissue pressure balance in the kidney glomerulus
Only filtration takes place.
The capillary pressure in the glomerulus is very high due to the need to filter lots of plasma.
Means the hydrostatic pressure is always greater than the oncotic pressure.
Describe the tissue pressure balance in the pulmonary capillaries
Only reabsorption takes place.
The pulmonary capillary pressure is very low as right side of heart has a weaker contraction.
Means the hydrostatic pressure is always lower than the oncotic pressure.
What is oedema and why does it occur?
Oedema is an imbalance of tissue fluid.
Occurs when filtration is greater than reabsorption and lymph drainage.
How does increased venous pressure cause pitting oedema?
What are its causes?
Hydrostatic pressure in the venous end increases. This means the hydrostatic pressure gradient doesn’t decrease below the oncotic pressure enough for reabsorption.
Can occur due to cardiac insufficiency, heart cannot produce enough pressure to pump blood around the body.
Can occur as a result of thrombotic blockage.
How does inflammation cause oedema?
Insect bites and sepsis can lead to release of mediators (bradikynin, thrombin, histamine).
These cause vasodilation in the arteriole part of the capillary so more blood arrives, increasing the pressure.
The tight junctions in the endothelial cells increase the permeability of the capillary.
Both of these actions increase the filtration in the arteriole side of the capillary, resulting in oedema.
How does reduced plasma protein levels cause oedema?
Reduced protein concentration in the capillary means that the hydrostatic pressure will be higher than the oncotic pressure for a greater length of the capillary, meaning there will be more filtration and less reabsorption.
Can occur in liver failure to produce albumin, malnutrition or nephrotic syndrome.
How does reduced lymph drainage cause oedema?
No drainage of lymphatic vessels means that the 3L of lymph produced per day will accumulate in the interstitial fluid.
This can lead to fibrotic scan tissue around the oedema area.
Can occur due to bancroftian filariasis, lymph node destruction.
How does a haemorrhage cause increased blood volume?
The haemorrhage causes a great reduction in blood volume, so the hydrostatic pressure in the capillary decreases.
Means the hydrostatic pressure will not be greater than the oncotic pressure for enough length of the capillary.
Results in more reabsorption than filtration, in order to try and increase the lost blood volume.
How is hypertension defined in mmHg?
When systolic pressure is over 140mmHg and diastolic pressure is over 90mmHg.
How is atherosclerosis affected by hypertension?
Increased pressure increases chances of things dislodging from the wall of the vessel and entering the circulation.
What happens to systolic blood pressure as you age?
It increases
What are the protective properties of oestrogen?
Oestrogen is protective to vasculature as it inhibits smooth muscle proliferation and promotes growth of endothelial cells.
List 4 consequences of hypertension
1) Increased cardiac work (due to more after load)
2) Ventricular hypertrophy
3) Increased distension of vasculature
4) Increased peripheral resistance
How does a higher blood pressure affect after load?
It increases the after load
How does an increase in after load affect the heart? (full explanation)
1) The pressure that ventricles have to exceed to force blood out is higher, so the end diastolic pressure is higher.
2) Means the ventricle has to stay in the isovolumetric contraction phase for longer to generate more pressure to exceed the end diastolic pressure.
3) The point at which the ventricular pressure falls below the aortic pressure is now higher, therefore less blood is ejected in each stroke.
How does an increase in after load affect the heart? (short answer)
Heart has to do more work to eject a smaller volume of blood, resulting in reduced cardiac output.
What factor determines the stroke volume?
The venous return to the heart
Define secondary hypertension
There is an identifiable cause of the decrease in cardiac output.
What is pheochromocytoma?
A tumour of chromaffin tissue which secretes adrenaline and noradrenaline, resulting in vasoconstriction therefore increased blood pressure.
How is pheochromocytoma treated?
Surgery or adrenoreceptor antagonists
How can a tumour of the anterior pituitary secrete that secretes excess adrenocorticotropic hormone cause secondary hypertension?
It stimulates the adrenal cortex to release more cortisol, resulting in the Cushing’s reflex so hypertension.
What is another hormone the adrenal cortex secretes other than cortisol that can increase blood pressure?
Aldosterone
How can balloon angioplasty reduce hypertension?
It widens the narrowing of the aorta to allow more blood flow.
Define primary hypertension
No identifiable cause. Can just start as increased tissue perfusion, but then it will affect cardiac output.
What is the main method of treating primary hypertension?
Lifestyle changes of exercise, reduced salt intake, reducing weight.
Outline the theory behind hypertension
1) The cerebral vascular resistance increases.
2) This decreases the cerebral perfusion, brain doesn’t not have enough oxygen.
3) This increases the sympathetic activity to increase blood pressure through vasoconstriction to increase the perfusion.
4) This increases the cerebral vascular resistance, which can then promote oxidative stress and inflammation, which causes the cycle to repeat again.
List other environmental factors other than deccreased cerebral perfusion that causes increased vascular resistance
1) Inulin resistance/diabetes
2) Obesity
3) Renal perfusion - or lack of
Why does the sympathetic nervous system affect the cardiac output and the total peripheral resistance?
There are beta receptors on the heart and alpha receptors on the vasculature, which increase the heart rate + stroke volume and cause vasoconstriction.
What is orthostatic intolerance?
When there is no autonomic control over the cardiovascular system when it is needed.
How does the renin-angiotensin system cause hypertension? (full explanation)
1) The release of renin from the granular cells of the juxtaglomerular apparatus causes the cleavage of angiotensin (form liver) to angiotensin 1.
2) Angiotensin cleaving enzymes from the pulmonary endothelium then cleave angiotensin 1 to angiotensin 2.
3) Angiotensin 2 stimulates the release of aldosterone from the adrenal cortex.
4) This induces Na+ retention, which in turn increases the reabsorption of water, which will increase plasma volume.
5) This in turn increases venous return so increases cardiac output.
6) Aldosterone also increases vasoconstriction of blood vessels, therefore increasing the total peripheral resistance.
What are the main 2 types of drugs used in hypertension to target the sympathetic nervous system?
1) Alpha 1 antagonist to prevent vasoconstriction
2) Beta 1 antagonist to decrease the cardiac output
3) Beta 2 receptors to increase vasodilation
Give an example of a alpha 1 agonist
Prazosin
Give and example of a beta 1 antagonist
Propanlol
What are the 2 effects of angiotensin 2 on angiotensin receptors?
1) Induces vascular growth (hypertrophy and hyperplasia)
2) Vasoconstriction (from direct release of noradrenaline)
3) Increased salt retention (from aldosterone release)
What 3 types of drugs can be used to treat hypertension that target the renin-angiotensin system?
1) ACE inhibitors
2) Angiotensin 2 antagonists
3) Aldosterone antagonists
How do ACE inhibitors treat hypertension?
Prevents the production of angiotensin 2 in the first place.
How do angiotensin 2 antagonists treat hypertension?
Prevents vasoconstriction
Prevents aldosterone release
How do aldosterone antagonists treat hypertension?
Prevents the reabsorption of salt so blood plasma volume does not increase
List 4 determinants of stroke volume
1) Preload
2) Heart size
3) Contractility
4) Afterload
Where are blood pressure receptors located?
1) Baroreceptors in the arch of aorta and carotid bodies
2) Kidneys
3) Stretch receptors in the heart and vessels
How does decreased blood pressure affect urine output?
It decreases the urine output
How does decreased blood pressure affect lactate production?
It increases lactate production
Outline how hypovolaemia occurs
1) Loss of blood occurs, decreased venous return to the heart.
2) This decreases the preload of the heart.
3) Because of Starlings principle, this means the stroke volume and contractility of the heart is decreased.
4) This decreases the cardiac output therefore the blood pressure also is decreased.
5) This can lead to organs not being perfused, therefore causing organ failure and death.
What are the 2 main ways the body responds to hypovolaemia?
1) Increased heart rate to maintain the cardiac output even though there is a decreased stroke volume.
2) Increase in total peripheral resistance through vasoconstriction to maintain the mean arterial pressure.
What is the baroreceptor response to the parasympathetic nervous system?
It decreases the parasympathetic stimulation to the heart, to increase the heart rate.
What is the baroreceptor response to the sympathetic nervous system?
Increases the cardiac stimulation and peripheral artery stimulation
What do the baroreceptors do to the cardiac muscles?
Increases the contractility
Increases the heart rate (SA node depolarisation)
What do the baroreceptors do the the peripheral arteries?
Causes vasoconstriction to the veins and arteries
Increases the venous return to the heart
Outline what happens to baroreceptors when the blood pressure increases
1) Increased stretch of baroreceptors.
2) More impulses fired to the vasomotor.
3) Inhibits the sympathetic innervation to the heart, so the vagal tone of the heart increases.
4) Firing of the SAN reduces, so heart rate reduces in order to reduce the increase in blood pressure.
5) No vasoconstriction of the peripheral blood vessels.
Outline what happens to the baroreceptors when the blood pressure decreases
1) Decreases tension in the stretch of the baroreceptors.
2) Less impulses sent to the vasomotor of the brain.
3) This stops inhibition of the sympathetic nervous system, so there is less parasympathetic influence on the heart.
4) Firing of SAN increases to increase the blood pressure back to normal.
5) Sympathetic nervous system activates the alpha 1 receptors to cause vasoconstriction.
How does the secretion of ADH treat hypovolaemia?
1) Increased ADH secretion from the pituitary gland
2) ADH acts on the V2 vasopressin receptors on the principle cells on the collecting tubule.
3) Results in more production of AQP2 and more vesicles of AQP2 fusing with the luminal membrane wall.
4) More AQP2 increases water retention, to then increase the plasma blood volume.
How does an increase in stress treat hypovolaemia?
1) Stress increases secretion of hormones cortisol and adrenaline from the adrenal glands.
2) Adrenaline increases the contractility (ionotropy) of the heart, and increases the arterial vasoconstriction.
3) Cortisol acts on aldosterone receptors to increase salt therefore water retention, which in turn increases the blood plasma volume.
How can the renin-angiotensin system treat hypovolaemia?
1) The decrease in blood pressure activates the granular cells in the juxtaglomerular apparatus to release renin.
2) Renin cleaves angiotensin to angiotensin 1.
3) ACE cleaves angiotensin 1 to angiotensin 2.
3) Angiotensin 2 causes secretion of aldosterone from the adrenal glands.
5) Aldosterone increases the number of ENaC channels on the principle cells of the collecting tubule, resulting in more salt retention, leading to more water retention.
Where does resistance in blood vessels arise from?
From the frictional force of the luminal surface of the blood vessel and the blood.
What 3 factors affect the resistance of blood vessels?
1) Vessel length
2) Vessel diameter
3) Blood viscosity
What is the relationship between the arteriole radius and the resistance in the blood vessels?
The resistance in blood vessels is inversely proportional to the radius to the power of 4.
(In increase in the radius by 1 decreases the flow by a sixteenth of what it originally was.
Does the blood flow differ within the lumen of blood vessels?
Blood flow is faster in the centre and slower around the edge of the lumen.
Which blood vessels are termed the ‘resistance vessels’?
Arterioles
Why are arterioles termed ‘resistance vessels’?
Because there is a large fall in pressure and velocity in this region of the blood flow.
What adaptation of blood vessels allows fro small vessels to deal with high pressures?
As resistance of vessels increases, the thickness of the wall increase in comparison to its lumen.
What is located in the tunica intima in the arterioles?
Endothelial tissue
What is located in the tunica adventitia of arterioles?
Nerves
What is located in the tunica media?
Vascular smooth muscle
Outline the mechanism of smooth muscle contraction
1) There is a rise in the concentration of intracellular Ca2+ either through calcium channels or intracellular stores of Ca2+.
2) The Ca2+ then binds to a protein called calmodulin, which forms a complex.
3) The complex then binds to myosin light chain kinase.
4) Myosin light chain kinase phosphorylates the myosin light chains on the myosin heads. This allows ATPase activity to occur.
5) Cross bridging of actin and myosin can then occur, which allows contraction through the pulling action of myosin on the actin filaments.
What is the difference between smooth muscle and striated muscle contraction?
Striated muscle contraction also involves troponin, smooth muscle contraction does not.
List the 4 types of receptors that allow the entry of Ca2+ into smooth muscle cells
1) Gq protein linked receptors that are stimulated by noradrenaline.
2) Ligand gated Ca2+ ions channels stimulated by ATP.
3) P2x purinoceptors
4) Non selective cation channels that are stimulated by stretch of the muscle
How are depolarisation waves spread between smooth muscle cells?
Once one cells depolarises, the wave spreads along adjacent cells between gap junctions.
How can hypertension be treated by inhibition of Ca2+ channels?
Blockers of the L type Ca2+ voltage gated channels help to reduce calcium influx into vascular smooth muscle.
This then inhibits vasoconstriction, which would reduce peripheral resistance therefore treating hypertension.
What is extrinsic control of circulation?
Nervous and humoral control of the vascular resistance in the circulation as a whole.
Regulates distribution of blood flow to different organs/tissues.
What is local control of circulation?
Different smaller factors that allow an individual vascular bed to regulate blood flow according to its own needs.
Which branch of the autonomic nervous system mainly innervates vascular beds?
The sympathetic nervous system
What does nervous control of circulation involve?
Sympathetic and parasympathetic nervous systems
What does humoral control of circulation involve?
Adrenaline
Angiotensin II
Vasopressin
Natriuretic peptides
What does local control of circulation involve?
Endothelium derived factors
Direct stimulation through stretch
Metabolic factors
Which hormone stimulates smooth muscle contraction of arterioles?
Noradrenaline
What controls how much noradrenaline is secreted therefore how much vasoconstriction and resistance occurs?
The frequency of signals from the sympathetic nervous system.
More signals = more contraction = more vasoconstriction = less blood flow
List 4 other factors apart the baroreceptors system that increases vascular sympathetic stimulation
1) Chemoreceptors that detect hypoxia / hypercapnia.
2) Skeletal muscle receptors during exercise.
3) Visceral and cutaneous nociceptors that detect noxious or painful stimuli.
4) Mental stress
What are cutaneous arterioles?
Arterioles found near the skin.
What stimulates cutaneous arterioles to vasoconstrict?
Hypothermia and emotional stimuli
Are cutaneous arterioles baroreceptors sensitive?
No
Does the parasympathetic nervous system block vasoconstriction?
No, its function is mainly vasodilation
Where are the muscarinic receptors for vasodilation found on the blood vessel?
On the endothelium (as opposed to the smooth muscle like the sympathetic nervous system)
What is the main neurotransmitter for vasodilation?
Nitric oxide
Outline the mechanism of vasodilation
1) Rise in Ca2+ levels in the endothelial cells of the blood vessels stimulates nitric oxide synthase.
2) Nitric oxide synthase produces nitric oxide.
3) Nitric oxide diffuses into smooth muscle cells and stimulates guanine cyclase.
4) Guanine cyclase causes a rise in the concentration of cyclic guanosine monophophate (cGMP).
5) Increased levels of cGMP results in relaxation of the smooth muscle cells, therefore vasodilation.
What are 2 other ways that the nitric oxide synthase enzyme can be activated?
1) Muscarinic receptors on endothelial cells can be stimulated by Acetylcholine, which activates the nitric oxide synthase enzyme. Overall results in more cGMP present in the cell.
2) Parasympathetic activity can increase the Ca2+ concentration at the end of an axon terminal. This increase concentration if the nitric oxide synthase enzyme. Overall results in more cGMP present in the cell.
How does viagra affect the mechanism of parasympathetic vasodilation?
Viagra prevents the breakdown of cGMP. Buildup of cGMP prevents relaxation.
Is humoral control faster or slower in controlling vascular resistance than the autonomic nervous system?
It has slower effects than the autonomic nervous system.
How does adrenaline affect vasoconstriction and vasodilation?
1) It can stimulate beta 2 receptors in the arterioles of skeletal muscle and the heart. Causes vasodilation.
2) It can stimulate alpha 1 receptors in the arterioles of peripheral vascular beds. Causes vasoconstriction.
Where is adrenaline secreted from?
The adrenal gland
What stimulates adrenaline secretion?
Exercise, emotions, pain, excitement
Does angiotensin II cause vasoconstriction of vasodilation?
Only vasoconstriction!
By which 2 mechanisms can angiotensin II increase blood pressure and vasoconstriction?
1) Directly causes vasoconstriction and increases sympathetic stimulation (which can lead to more angiotensin II release).
2) Angiotensin II can stimulate aldosterone to reabsorb more Na+ from the collecting tubules of nephron. This reabsorbs more water, thereby increase blood volume and blood pressure.
What 2 factors affect the release of vasopressin?
1) Increased osmolarity - osmoreceptors
2) Decreased blood volume/pressure - baroreceptors
Where is vasopressin (ADH) released from?
The hypothalamus stimulates vasopressin release form the posterior pituitary gland.
By which 2 mechanisms does vasopressin increase the blood pressure and decrease the osmolarity?
1) Vasopressin causes vasodilation in the brain and heart and vasoconstriction on V1 receptors on smooth muscle.
2) Stimulates more water reabsorption from the collecting tubules through AQP2.
Which function of vasopressin is more dominant?
The reabsorption of water from the collecting tubule by stimulating V2 receptors to increase membrane AQP2.
Do natriuretic peptides cause vasoconstriction or vasodilation?
Only vasodilation!
What are the 2 natriuretic peptides and where are they released from?
1) Atrial natriuretic peptides released from the atria
2) Brian natriuretic peptides released from the ventricles
What stimulates release of natriuretic peptides?
Stretch of the receptors in response to a greater blood volume.
Outline the mechanism of how natriuretic peptides reduce the blood pressure?
1) ANP and BNP stimulate NPR-A and NPR-B. These are guanylate cyclase receptors on vascular smooth muscle.
2) The guanylate cyclase receptors are linked to increasing cyclic GMP.
3) They also stimulate natriuresis so there is more excretion of salt and water from the kidney.
Which 2 places can local control of blood vessels act?
1) Endothelium
2) Vascular smooth muscle
List 4 factors that effect endothelium dependent vasodilation
1) Nitric oxide
2) Prostacyclin
3) Endothelin derived hyper polarisation factor
What is a factor released by the endothelium that causes vasoconstriction?
Endothelin
List 4 stimuli that can stimulate the endothelium factors
Hypoxia
Shear stress
Autocoids (hormone that acts where it is synthesised)
Blood flow
What is shear stress?
The force per unit area when the tangential force of blood flow acts on the endothelium.
What happens to shear stress when there is an increase in blood flow?
The shear stress also increases
Why is exercise beneficial in terms of shear stress?
Exercise increases shear stress in blood vessels.
Shear stress stimulates production of NO.
NO has protective actions against atherosclerosis, therefore is beneficial.
Outline the process of vasodilation through nitric oxide
1) Stimulation of the endothelial cells causes nitric oxide synthase to release nitric oxide.
2) Nitric oxide stimulates soluble guanine cyclase in the vascular smooth muscle cells.
3) This increases the production of cGMP, resulting in smooth muscle relaxation.
Outline the process of vasodilation through prostacyclin
1) Stimulation of endothelial cells stimulates the enzyme cycloxygenase.
2) This enzyme produces many prostaglandins.
3) These prostaglandins enter the smooth muscle cells via Gs protein receptors.
4) This intiates adenyl cyclase to produce cAMP, which results in smooth muscle relaxation.
Outline the process of vasodilation through EDHF
1) Stimulation of endothelial cells causes the production of EDHF.
2) EDHF causes hyperpolarisation of the smooth muscle cells, which closes the Ca2+ on the smooth muscle.
3) Results in relaxation of the smooth muscle.
What factors of the immune system can cause vasodilation in inflammation?
Mast cells and basophils release histamine and bradykinin which cause vasodilation though the NO pathway.
What do platelets release when forming clots to cause vasodilation?
Platelets release autocoids of ADP, 5-HT and thrombin.
These cause vasodilation through the NO pathway so that vessels are not drastically narrowed from blood clotting.
What is endothelin?
A peptide
List 5 factors that can stimulate endothelin
Angiotensin II Vasopressin Thrombin Cytokines Shear stress
Is endothelin the most long lasting endogenous vasoconstrictor?
Yes!
What are the overall effect of endothelin?
1) At low levels endothelin stimulates endothelia receptors that cause release of NO, causing vasodilation.
2) At high levels endothelin stimulates Gq receptors on the smooth muscle, resulting in vasoconstriction.
Where does autoregulation take place?
In the brain
What is the function of autoregulation?
It allows blood flow to remain at a constant level as it stimulates vasoconstriction when the perfusion pressure increases.
What stimulates autoregulation to cause vasoconstriction?
Increased blood flow due to perfusion pressure causing stretch in stretch activated non selective cation channels.
Where does functional hyperaemia occur?
In skeletal muscle, myocardium and brain
What is the purpose of functional hyperaemia?
This mechanism increases blood flow when there is an increase in metabolic demand eg. exercise
What factors cause vasodilation in functional hyperaemia?
Adenosine
H+
CO2
K+
What is the purpose of reactive hyperaemia?
Increases blood flow after a interruption of blood flow. This is to remove the build up of metabolites that stimulate vasodilation.
What factors cause reactive hyperaemia?
Hypoxia
Metabolites
Mediators released from surrounding tissues
