HOM Revision Notes 6 - Fraser Heart and Circulation PDF

Preview

Summary

Download HOM Revision Notes 6 - Fraser Heart and Circulation PDF

Description

Fraser: Heart and Circulation Heart’s control of cardiac output • • • • • •

Heart has little control over cardiac output. Guyton et al (1957): Replaced hearts of dogs with high output pumps. Unsurprisingly reducing pumping capacity below normal reduced cardiac output. However, increasing the pumping capacity did not increase cardiac output. Shows that: heart is necessary to maintain CO, but does not normally limit CO.

Flow in closed system • •

• •

MSFP= the mean systemic filling pressure. As flow= (PA- PV)/R if PV becomes negative ie transmural pressure is negative, veins will collapse. If veins collapse then this will cause resistance to flow. In real veins, will collapse if pressure drops about 1 or 2 mm Hg below atmospheric pressure.

• Therefore, if heart increase PA too much, PV will drop too low, this limits venous return, thus reduces cardiac output. • Therefore, mean systemic pressure is the main determinant of cardiac output. • Direct measurement of right atrial pressure confirms that a healthy heart will reduce central venous pressure to almost zero, ie increase PA to max CO at fixed MSFP.

Heart rate and Cardiac Output •

Increasing heart rate or myocardial contractility will not increase cardiac output without an increase in venous return. In diagram below venous return is increased by reducing resistance by directly connecting aorta to vena cava.

Mean systemic filling pressure and cardiac output • • • • •

As shown above, the mean pressure determines the maximum flow rate for a given resistance. MSFP may be increased by increasing circulating volume of blood, or by reducing volume blood has to flow through. Ie splanchnic stimulation causes venoconstriction, low- med and high refer to circulating volume. Shows that an increased MSFP increases cardiac output. In reality, venoconstriction can reduce volume for blood to flow through, and fluid retention/absorption can increase blood volume.

Blood volume and mean filling pressure in real life • •

•

Normal blood volume is approx. 70-80ml/kg ie 5L for 70kg person. If this volume is added to an empty system: first 80% does not cause an increase in pressure- pressure stays at zero until walls begin to stretchUnstressed volume. Last 20%- mean pressure will rise- stressed volume- normally gives rise to a mean pressure of 7-10 mmHg in circulation.

Effect of cardiac activity • •

•

• • • •

When blood enters vessels, pressure changes according to their compliance. Veins are very compliant in physiological range (however become very stiff when overstretched). This ensures that the reduction in venous pressure during cardiac activity is relatively small compared to without cardiac activity. However, movement of blood into less compliant arteries causes a large increase in pressure. This means that when heart is working normally the arteries are more filled and the veins less filled than they would be if the heart stopped. (Arteries are stretched, elastic). The arteriovenous pressure gradient drives the blood flow around the body. Maximum arteriovenous pressure gradient is set by the mean filling pressure hence: heart cannot change the MSFP and the MSFP determines the cardiac output.

Control of cardiac output • • • •

Key point of control: RAP If CO stayed constant, then an increase in MSFP would increase RAP, however in real life CO would also increase due to Starling mechanism. Implications of starling mechanism: Increased MSFP causes increased CO, conversely decreased MSFP will also decrease CO. Heart rate effects: If increases in isolation, SV drops, CO barely changes.

•

However, in exercise increased heart rate facilitates increased cardiac output by shifting curve of CO vs RAP.

Control of MSFP • • •

•

• •

MSFP is determined by the volume of blood and the mean transmural tension. MSFP can be doubled by increasing the blood volume by 20% as doubles stressed volume. As about 60% of blood is in the venules and small veins, venoconstriction can reduce the capacity of the circulation. This means MSFP can be maintained above zero even when 40% of circulating volume is lost eg during bleeding. Accomplished by sympathetic venoconstriction. Can treble MSFP. As TPR is primarily determined by arterioles, venoconstriction does not influence TPR.

Resistance to venous return •

•

• •

If consider circulation as two halves ie part when pressure is above MSFP and part when it is below: CO= (ABP- MSFP)/TPR VR= (MSFP- RAP)/ RvR RvR: capillary pressure in feet is insufficient to drive blood upwards to the heart more than a meter. Therefore venous return from lower legs is dependent on voluntary muscle movement. Therefore RvR can be decreased by walking, running or lying down. Venous return equation produces the following graph:

• • •

When the VR =0, the RAP = the MSFP. Hence increasing MSFP shifts the curve up. Reducing RvR would increase the slope without changing MSFP. RAP influences both VR and CO via the starling mechanism. When both graphs are plotted together it shows the actual CO, VR and RAP. (Shows RAP is just above zero).

•

If RAP was 5 mm Hg, cardiac output would exceed venous return, which would cause RAP to drop, until VR and CO were equal.

•

B: venoconstriction increases MSFP, hence VR curve is shifted upwards. Means for a moment VR exceeds CO but as this increases RAP, CO subsequently increases. C: Cardiac output shifts to higher outputs at any RAP. However as this drives RAP negative, increase in CO is minimal. D: combining both effects creates greatest increase in cardiac output.

• •

Cardiac output in cardiac disease • •

If heart cannot increase CO ie myocardial necrosis/ infarction- MSFP would increase RAP but CO could not increase. If RAP increases then capillary pressures must also increase- results in oedema due to extravasation of fluid.

• •

• • •

This is why a diuretic may be given to people in position C in order to reduce VR and thus RAP. Shock- defined as when CO is insufficient to adequately perfuse organs. Typical signs are hypotension and tachycardia (heart rate exceeds normal) with low urine output and loss of consciousness. Can result from cardiac output failure. Hypovolaemic shock- severe loss of circulating volume. Cardiogenic shock- due to cardiac pathology. Distributive shock- occur due to severe fall in vascular tone and extravasation of plasma, which by reducing MSFP has similar effects as hypovolaemia. Can be caused by septicaemia. anaphylaxis or failure of sympathetic innervation eg when spinal cord is severed.

Arterial blood pressure • • •

Principle variable controlled by the cardiovascular system. Blood flow to individual tissues can be regulated by controlling local resistance ie through vasoconstriction/dilatation. Q= ∆P/ R, ∆P is roughly constant. As APB= CO x TPR, TPR and CO are the main determinants of blood pressure, these can be affected by blood loss or exercise. Therefore must be a mechanism of controlling ABP.

ABP during heart beat • • • •

Heart pumps blood into aorta, increasing pressure to peak systolic, around 120 mmHg. Creates ∆P towards rest of body, blood flows away. Aortic pressure reduces to trough value of 80 mmHg before next heart beat then increase again. Aortic valve leak may cause a massive increase in max ABP but also a quicker loss of pressure. Results in eg 170/ 40 mmHg.

• • • • •

Mean blood pressure= diastolic pressure + 1/3 pulse pressure. Pulse pressure is the difference between the systolic and diastolic pressures. Increases with age, exercise, male, aortic valve leak. Increases if arterial compliance reduces eg atherosclerosis. In situations where the pulse pressure increases- mean pressure stays constant (ie systolic pressure increases as diastolic pressure falls)- this is evidence that APB is the principally regulated variable.

Regulation of mean ABP • •

TPR is primarily a function of arteriolar resistance, does not greatly affect CO due to starling mechanism. Thus CO and TPR are largely independent and are individual ways of controlling BP.

High pressure baroreceptors • •

•

•

•

Located in carotid sinus + aortic sinus. Stretch- sensitive nerve endings are intermeshed within elastic lamellae in regions with relatively little collagen and smooth muscle. Stretch triggers deformation of nonselective cation channels of TRP family- eg TRPC1. Increased activity in glossopharyngeal nerve (carotid sinus) + vagus (aortic nerve). Stimulate neurons in Nucleus Tractus Solitarius (NTS) via AMPA – this then stimulates inhibitory interneurons to the vasomotor centre (reduced vasoconstriction) and excitatory interneurons to the cardioinhibitory centre (decreases HR). Consists of nucleus ambiguus + Dorsal motor nucleus of vagus. Different baroreceptors have different sensitivities to blood pressure. (Carotid sinus is more sensitive than aortic arch, aortic arch can respond at pressure above which carotid sinus saturates.

• • • • •

• •

Heymans Cross circulation experiments: carotid sinus of dog B was connected into the circulation of dog A. Injection of adrenaline into dog A triggered a reflex fall in BP in dog B. High pressure baroreceptors and chemoreceptors are important in the short-term control of ABP. Denervation of baroreceptor- ABP increases variability, mean stays the same. If ABP changes, high pressure baroreceptors reset and regulate around new ABP. Baroreceptors are very receptive to sudden change, not so responsive to short changes over time- thus may become hypertensive- due to accommodation of nerve fibres. Resetting: may occur centrally during exercise, also peripheral reset eg sustained increased ABP- right shift of curve. BP of foetus is much lower than post-natal- around 40mmHg – then reset over a period of weeks to normal 100 mmHg.

Arterial and central chemoreceptors • • • • •

Chemoreceptors in carotid and aortic bodies primarily regulate ventilation. Don’t normally regulate BP, only have role when BP is very low or when PO2 is significantly reduced. Influence important as high pressure receptors are relatively unresponsive in severe hypotension. Carotid and aortic bodies detect low O2 delivery- medullary chemoreceptors detect high arterial CO2 via pH drop in brain. Afferent signals travel via same nerves as baroreceptors.

Low pressure baroreceptors • •

• • • •

• •

•

MSFP is important in ABP determination, therefore stretch receptors exist in strategic lowpressure areas- junctions of atria with corresponding veins, and the atria themselves. B fibres are located at the end of the superior and inferior venae cava, increase in firing rate as atria fill, reach peak frequency at v wave of atrial pulse and thus measure atrial vol and CVP most accurately. Collectively called cardiopulmonary baroreceptors. Essentially detect RAP- if raised, circulation is overfilled, heart cannot maintain low venous pressures. Seen in heart failure, can lead to oedema. If low- CO is maximal for current MSFP. Firing rates increase with pressure- travel via vagus nerve to NTS in medulla and then to magnocellular neurons of the paraventricular nucleus of the hypothalamus. Influence secretion of ADH (arginine vasopressin), sympathetic activity, thirst, sodium appetite. When denervated – variability increase+ mean BP increases independent of functioning High pressure baroreceptors. (evidence that HP baroreceptors don’t control MAPB). Also stretched atrial myocytes release atrial natriuretic peptide which is a powerful vasodilator, and causes diuresis by enhancing renal secretion of Na+.

•

Nb increased stretch of fibres will stimulate heart rate unlike high pressure receptors.

Summary • •

High pressure baroreceptors respond to increased stretch by trying to decrease ABP. Low pressure baroreceptors respond to stretch by attempting to eliminate fluid. Net effect of atrial stretch (tachycardia and renal vasodilation), is an increase in renal blood flow.

Non-feedback control systems • • •

•

Exercise, standing up and moderate blood loss do not cause detectable drops in ABP. These common stresses trigger feed-forward mechanisms to preserve ABP. Exercise: drop can be prevented by inputs to medulla from cortex (decision to exercise), from cerebellum (co-ordinates motor programme) and from muscle and joint receptors (direct response to movement). Pain and emotion- involve cortex + hypothalamus- provoke rise in blood pressure through sympathetic action.

Integration of baroreceptor and “feed-forward” signals in medulla •

Both signals feed into the medulla.

Neural autonomic control • • • •

• •

Claude Bernard- section of sympathetic nerves leads to vasodilation in the ear vessels of rabbits- showed sympathetic tone is necessary for vascular resistance. Brown- Sequard: showed sympathetic tone increases vasoconstriction. Owsjannikow + Ditmar- stimulation of peripheral end of sciatic nerves- produce vasoconstriction in skin and splanchnic bed- increases BP in cat. Vasomotor centre: discovered by Owsjannikow + Ditmar: carried out transections: rostral transection- no effect on BP regulation, caudal transection (below pons, above medulla)could not maintain BP. Shown centre consists of a pressor region:- stimulation of which will increase BP, and a depressor region: stimulation of which will decrease BP through inhibition of pressor region. Chemoreceptors act on pressor region, baroreceptors on depressor region.

Vasoactive neuronal pathways • • • • • • • • •

70% of vasoconstrictor nerves are sympathetic: (NA release during constant discharge, NPY during bursts). Vasodilator nerves: Sympathetic (β2), parasympathetic (ACh), dorsal root. Bullring and Burn preparation: attached a dog- hind limb to a pump, stimulated femoral nerve to see how affected perfusion in the circuit. First experiment: stimulated- initial increase in BP- followed by decrease- concs: group of neurons, some constrictor, some dilators. Second experiment: repeated in presence of eserine (ACh-esterase inhibitor)- found enhanced vasodilator response: concs: ACh release responsible. Third experiment: eserine+ atropine – no response. Only recently shown to be present in humans. Local parasympathetic dilation important for eg salivary glands/ genitalia- don’t want a reduction in BP but need increase BF to organs. These fibres may be important for salivary and some gastrointestinal glands- crucial for vasodilation in erectile tissue.

Effector pathways • •

Medulla generates response through sympathetic- to vasculature and heart, and parasympathetic- solely to heart. Other autonomic pathways are involved in the control of local blood flow.

Sympathetic efferents •

•

•

•

• • • • • •

Bulbospinal pathways activate preganglionic pathways, primarily at glutamatergic synapses between levels T1 and L3. Preganglionic neurons synapse at nicotinic synapses with postganglionic sympathetic neurons found within prevertebral and paravertebral ganglia. Postganglionic nerves run with large blood vessel to innervate muscular arteries, arterioles and veins. Increased sympathetic activity generally causes vasoconstriction though action of α1 adrenoreceptors. Gq coupled to receptorstimulates phosphoinositol signalling pathway which causes Ca2+ release from IP3 receptor. Arteries and arterioles of brain show little vasoconstriction. Increase of tone to 10Hz can reduce blood flow to some tissues to zero in extreme circumstances such as haemorrhage. Spinal cord damage above T1 causes a severe rapid drop in BP by abolishing resting sympathetic outflow. Fibres increase heart rate and contractility- low resting frequency. Some fibres in the splanchnic nerves innervate chromaffin cells in adrenal medulla stimulating adrenaline release. Adrenaline: acts on heart + vasculature in similar way to direct sympathetic innervation.

Parasympathetic • • • •

Vagus nerve innervates SA node, AV node + cardiac conducting system. Slows heart rate, slows conduction through heart and lengthens cardiac cycle. Does not influence force of contraction. Muscarinic- blocked by atropine- if vagus is inhibited produces a significant acceleration of heart rate.

Integration and effectiveness of circulatory control •

• •

Fall in TPR → demand increase in CO → sympathetic venoconstriction → increase MSFP + increased sympathetic and reduced vagal stimulation of heart to increase heart rate and contractility (ensures raised MSFP produces a rise in CO without necessitating an increased RAP) → Increased CO. All above control short term blood pressure. Circulating volume is a critical determinant of MSFP and thus ABP.

Control of capillary blood flow • • •

• • • • • • •

As Q=∆P/R- constant ∆P due to constant ABP means flow to capillary beds can be regulated by upstream arteriolar resistance. Three main regulatory mechanisms: nerves, hormone and other vasoactive substances, local tissue metabolism. Blood flow is well matched to metabolic demand- cardiac output is usually proportional to VO2, volume of oxygen used per min. VO2 can be used to measure CO in athlete studies. Varicose veins increase PV. Therefore, average P in capillaries increases and oedema may occur. As arteriolar resistance is the only directly regulated resistance- relationship can be simplified to: In general: local control of arteriolar resistance matches local blood flow to metabolic demand. Central, autonomic control of arteriolar resistance controls TPR to maintain constant ABP. Therefore may have opposing signals. Arteriolar smooth muscle: arranged radially, contraction increases tension causing vasoconstriction.

Control of arteriolar smooth muscle • • •

Two main areas of control: 1) regulation of myosin binding site by caldesmon. 2) regulation of myosin light chain by phosphorylation. Local control: Metabolic, myogenic, paracrine Systemic control: Sympathetic, Endocrine, organ specific mechanisms.

Metabolic control • • • • •

Functional hyperaemia: increase in blood flow when a tissue is active. Evidence: blood flow in arm measured, cuff applied for around 10 mins, when cuff is removed blood flow increases. Reduced PO2, increased PCO2, decreased pH, increased adenosine and increased extracellular K+ promote vasodilatation of arteriole. NB. Reduced PO2, increased PCO2 has opposite effect in lungs, indicates poor ventilation and not poor perfusion. Changes with anaerobic metabolism eg decreased pH and increased lactic acid conc cause vasodilatation.

Myogenic control • • • •

• •

If Blood vessels behaved as rigid tubes- flow would be proportional to ∆P Increased pressure leads to increased resistance- flow increases less than expected. This serves to maintain a constant capillary pressure. Particularly occurs in heart, kidney and brainmay reflect poor lymphatic drainage of heart+ brain and necessity to regulate filtration pressure in kidneys. Has similar affect to metabolic autoregulation. Therefore, increased arteriolar BP directly causes vasoconstriction by myogenic mech, also indirectly by washing out local metabolites.

Role of Endothelium • •

• • •

Optimal physical location to detect local changes in metabolism. Robert Furchgott’s experiments demonstrated that the vasodilatating effect of ACh requires an intact endothelium. ACh, vasodilator pept...