Coordinated Cardiovascular Responses: Orthostasis and Haemorrhage PDF

Life Sciences & Medicine Coordinated cardiovascular responses: orthostasis and Prof James Clark haemorrhage School of Cardiovascular and Metabolic Medicine...

Life Sciences & Medicine Coordinated cardiovascular responses: orthostasis and Prof James Clark haemorrhage School of Cardiovascular and Metabolic Medicine and Sciences PHYSIOLOGY AND ANATOMY OF SYSTEMS Learning Outcomes Understand the response of the cardiovascular system to orthostasis Understand the response of the cardiovascular system to haemorrhage Why blood continues to flow when you stand up – the siphon principle Flow is driven by an energy gradient with 3 components: hydrostatic pressure + gravity + kinetic lungs lungs LV LV RV RV 60 mmHg -10 mmHg 0 ~25 mmHg 95 mmHg ~4 mmHg 95 mmHg ~4 mmHg Flow will continue through a tube as long as the pump pressure is higher than the outflow pressure. In a closed system, if the tubes are rigid*the pressures between the outflow and the inflow of the pump do not affect the rate of flow. 180 mmHg 100 mmHg Another way to look at it: At any given level above or below the heart the arterial pressure will always be higher than the venous pressure, so blood flow will continue. *But blood vessels are not rigid… Orthosta 10 mmHg 4 mmHg Supine: mean capillary sis pressure ~25 mmHg 95 mmHg 95 mmHg 90 mmHg 1 mmHg Effect of upright posture on pressure in feet: during quiet standing: vascular pressures  by ~90 mmHg foot vein foot artery 105 185-105 = 80 185 105 mmHg 185 mmHg 120 Foot capillary pressure rises  filtration  feet swell BUT: pressure gradient across foot vascular bed unchanged, so flow is not directly affected by gravity. But indirectly, it is.  Fall in cardiac feet output head head The vascular system, particularly the veins, is distensible. When you stand, venous valves in the limbs shut transiently, (CO > return) which distends vessels below the heart After ~45 s the veins below the heart will contain 300-600 ml abdomen more blood. This opens the valves so that their blood flow into the heart upper recommences legs Central venous pressure is reduced (by ~3 mmHg), and therefore, by the Frank-Starling mechanism, cardiac output falls. feet Mechanisms limiting the Supine Upright Supine effects of orthostasis Orthostasis Heart rate 100 beats/min 60 blood distributes into veins of lower extremities Relative Stroke 1.0 Volume ↓stroke volume and CO, (ratio) 0.6 ↓ blood flow to the brain, Relative ↓ MABP in upper part of the body cardiac 1.0 output 0.8 (ratio) baro- and volume Systolic Change is minimised Blood 120 or reversed receptors pressure activated mmHg 80 Diastolic Relative 1.4 Total ↑ HR Peripheral 1.2 ↑ vasoconstriction resistance (ratio) 1.0 (in arteries and veins) ↑ TPR 0 10 20 30 40 Time (min) Vascular Responses to orthostasis Arteriolar constriction reduces blood flow on standing Two mechanisms are involved: reflex sympathetic vasoconstriction via baroreceptors (previous lecture) a local sympathetic axon reflex ‘Veno-arteriolar axon reflex’ i 105 ii 185 Reduces capillary 120 The skeletal muscle pump Heart valves Foot Can lower foot venous pressure to 20-30 mmHg. Makes an important contribution to the increase in blood flow during exercise Venous pressures in the foot when standing and walking 120 cm H2O  88 mmHg Valve failure in tributary superficial veinsexposes them to chronic high pressures, leading to varicose veins. 120 cm H2O  88 mmHg Levick JR, An Introduction to Cardiovascular Physiology. 5th edition, Arnold Venous pressures above the heart on standing Pressures in veins above the heart fall. Veins outside of the cranium collapse a few cm above the heart. Blood can still -10 mmHg flow through the margins of collapsed veins. The veins within the cranium do not collapse, and their internal pressures fall to about -10 mmHg. This helps to 0 mmHg maintain the pressure gradient driving the flow of blood to the brain. Pressure in veins when standing Blood flow to the brain falls by ~20% due to the drop in cardiac output. This can lead to fainting with prolonged standing, as pooling CVP ~ 1 mmHg of blood in the lower extremities gradually increases.  Why veins within the cranium don’t collapse? The brain and spinal cord are surrounded by cerebrospinal fluid (CSF). Gravity causes a downward displacement of the CSF within the subarachnoid space. This creates a negative intracranial pressure which prevents veins within the cranium from collapsing. http://www.control.tfe.umu.se/Ian/CSF/CSF_diagram.jpg Summary of typical CVS changes: supine to upright direct effects of venous pooling central blood volume - 400 ml central venous pressure - 3 mmHg stroke volume - 40% response Heart rate  25% Reflex Contractility  effect cardiac output - 25% Net Limb and splanchnic flow - 25% response Reflex total peripheral resistance - 25% usually only transient fall in blood pressure (= CO x TPR) reduced Cerebral blood flow - 20% CO Prolonged standing and postural hypotension Prolonged quiet standing → progressive venous pooling → progressive fall in pulse pressure → progressive rise in heart rate and TPR eventually mean BP starts to fall ↓ Sudden fall in TPR (due to vasodilatation) and heart rate ↓ Pooling of blood in the lower steep fall in BP & cerebral blood flow → syncope (faint) extremities after a head-up tilt.  This is a form of vasovagal syncope (vasodilatation) (vagally mediated bradycardia) Often preceded by symptoms such as pallor, sweating, nausea, blurred vision Fainting → horizontal, venous return restored  Vasovagal syncope TILT UP BP mmHg Heart Rate b.p.m. gradual fall in BP & sudden fall in BP & fall increase in HR in HR Vasovagal faint in KCL student – provoked by head up tilting combined with lower body negative pressure (increases venous pooling) Vasovagal Syncope What triggers the sudden change in the reflex response from tachycardia and vasoconstriction to bradycardia and vasodilatation? Exact trigger unknown, but thought to be due to the Bezold-Jarisch reflex (which can also be provoked by thrombolytic agents) One advantage of fainting is that it usually leads to a horizontal posture which instantly restores venous return and therefore cardiac output. But note: if for some reason the person remains upright (e.g., ‘helpful’ passenger holding them up as she faints on the tube) then BP will remain low and brain damage is possible. Haemorrhage = loss of blood Revealed haemorrhage: bleeding obvious although quantity often hard to measure accurately. Concealed haemorrhage: e.g., Ruptured spleen Fracture esp. pelvis and femur Trauma Renal damage Leaking aortic aneurysm Ruptured ectopic pregnancy Bleeding peptic ulcer Effects depend on volume and speed of blood loss: chronic, slow but persistent  Fe deficiency anaemia acute large loss  reduced circulating volume most important aspect is circulatory shock Circulatory shock Generalised inadequacy of blood flow throughout the body If prolonged, this is sufficient to cause tissue damage because of inadequate delivery of oxygen and other nutrients Most common cause is haemorrhage, but also: Other hypovolumic (burns, severe vomiting/diarrhoea) Cardiogenic (e.g. acute MI) Anaphylaxis Sepsis Note: The term “shock” does not simply mean low BP - although this is very often the cause of the hypoperfusion Signs, symptoms & consequences depending on severity Anxiety, restlessness, confusion, aggression, lethargy, coma Mistaken for being drunk? Rapid shallow breathing May have intense thirst Nausea Rapid (weak) pulse BP generally (but not always) low, pulse pressure always low Pale, grey or cyanotic, with clammy skin Reduced urine output Acidosis Also: Decreased coagulation time and increased neutrophils (after 2-5 hrs) Effects of different amounts of blood loss Blood Volume: ≈77 ml.kg-1 men, 67 ml.kg-1 women Therefore, blood volume of 70 kg male ≈ 5400 ml, female ≈ 4700 ml WHO Haemorrhage classification system < 3 cups Minimal: ≤ 15 % blood loss unlikely to elicit shock in a fit individual 4 - 6 cups Mild: 20-30% blood loss generally induces shock and BP may be depressed; not usually life-threatening 6 – 8 cups Moderate: 30-40% blood loss causes severe shock and a profound fall in BP and CO – may become irreversible (refractory) > 8 cups Severe: >40% blood loss means that death is generally inevitable However, severity is also related to rate of blood loss: a very rapid loss of 30% can be fatal, but 50% over 24h may be survived. Rapid compensatory responses to haemorrhage Act to minimise a fall in blood pressure Depend on four reflexes 1. High pressure baroreceptors: monitor BP in the carotid sinuses and aortic arch 2. Low-pressure baroreceptors: monitor blood volume in the heart and large pulmonary vessels 3. Peripheral chemoreceptors: located in the carotid and aortic bodies, sense ↓pO2 ↑pCO2 and ↓pH 4. Central chemoreceptors: sense ↓pH associated with reduced blood flow in the brainstem All act on medullary cardiovascular control centres to mount an autonomic response (mainly due to ↑ sympathetic drive but ↓ parasympathetic drive makes a contribution by increasing the HR. Rapid reflex responses to haemorrhage Results of reflex responses  Increase in heart rate and contractility tends to oppose the fall in cardiac output  Peripheral vasoconstriction, particularly of splanchnic circulation and also in the skin, kidney & muscles causes ↑ TPR  Mobilisation of blood from the splanchnic circulation due to vasoconstriction also tends to ↑ cardiac output  These effects ameliorate the fall in mean BP (but pulse pressure decreases)  Accompanying effects include:  pallor and cold/clammy skin due to sympathetically mediated vasoconstriction and stimulation of sweating  Fatigue due to reduced blood flow to muscle  Activation of the renin-angiotensin-aldosterone system due to renal vasoconstriction Baroreceptor reflex in haemorrhage  blood Baroreceptors pressure Brain stem Restores Parasympathetic HR  drive  Force  Cardiac output Sympathetic drive  Venoconstriction: CVP Vasoconstriction of splanchnic, skeletal muscle renal, skin : TPR Animal experiments show that if the sympathetic system is blocked, 15-20% blood loss in 30 min → death, whereas 30-40% blood loss can be survived if the sympathetic system is intact. Cardiopulmonary receptors respond to more severe blood loss Cardio-pulmonary stretch receptors, mechanoreceptors in the heart and large pulmonary vessels, respond to changes in blood volume. They activate reflexes which act to reverse the change in volume and support BP and CO. ↓ blood volume ↓ Stretch atria & Hypothalamus restores Cardio-pulmonary Medulla receptors ↑ Thirst, water reabsorption ↑CO ↑CVP ADH (vasopressin) Vasoconstriction ↑BP ↑TPR Adrenaline  (adrenals) Chemoreceptors and the CNS ischaemic response Peripheral chemoreceptors  respond to ↓pO2, ↑pCO2 and ↓pH. Afferents project to the nucleus tractus solitarius, activation triggers sympathetic vasoconstriction  Stimulation also increases ventilation. This causes lung stretch and also ↓CO2 these effects inhibit a medullary vagal control centre to cause tachycardia Central chemoreceptors/CNS ischaemic response (when mean BP < 50mmHg)  Chemoreceptors in the medulla sense ↓pH  Cause a very powerful sympathetic vasoconstriction of peripheral arteries and veins  Gut and renal perfusion severely reduced, dangerous if sustained Moderate Haemorrhage reduced cardiac output Aorta sympathetic Skin vasoconstriction coronary brain gut kidney muscle etc Vascular resistance: splanchnic, renal, skeletal muscle, skin:- increased cerebral and coronary :- normal/reduced Blood flow: splanchnic, renal, sk.muscle, skin :- reduced cerebral and coronary :- normal Arterial blood pressure: normal (low CO offset by high TPR): but pulse pressure is low Approximate changes in BP and CO vs. extent of blood loss over 30 min BP better protected as vital for tissue perfusion, but at expense 100 of diverting CO to key organs (brain, heart) % Initial (CO or BP) 50 CNS ischaemic response: BP  50mmHg Profound vasoconstriction via sympathetic 0 0 10 20 30 40 50 % Blood lost (in 30 min) Restoration of blood volume Example for moderate (25%) blood loss 100 Blood % Normal values volume 75 1 hr 1 day 3 days 1 week 3 weeks Recovery time Haemorrhage Restoring the blood volume “Internal transfusion” (hours) – Associated with haemodilution  Water intake (thirst)  Urine production (oliguria) days  Renal Na+ and water reabsorption Internal transfusion mechanism Depends on balance between hydrostatic and oncotic pressures (next lecture) When capillary hydrostatic pressure is reduced due to vasoconstriction and a fall in venous pressure Fluid is reabsorbed from the interstitium into the plasma, increasing blood volume (~0.5 litres) dependent on [plasma protein] NOTE: Fluid also moves from the intracellular to the interstitial compartments, driven by increased hepatic glucose production/release Renal mechanisms to restore blood volume Carotid  blood sinus pressure  Renin Baroreceptors  blood volume Hypothalamus  Ang Atria stretch Brain stem 2  Restor  ADH aldosterone e  ANP Thirst ADH release   Renal reabsorption of Na+ and water  Diuresis  reninAng2 Sympathetic renal aldosterone nerve activity    Na+ & water reabsorption ANP = atrial natriuretic peptide Restoring the quality of the blood Example for mid-moderate (25%) blood loss 100 Blood volume Plasma proteins produced in liver Red cells Erythropoietin % Normal values [Hb] (renal hypoxia) Reticulocyte count (normally 1-2% RBCs) peaks at 5-15% after 5-7 days 75 1 hr 1 day 3 days 1 week 4 weeks Haemorrhage Recovery time Restoring the Quality of the Blood Haemoglobin Blood [Hb] immediately after haemorrhage is normal – because both the number of RBC and the volume of plasma have fallen to the same extent. However, blood [Hb] falls over the 12-24 hours as the blood volume is restored whereas the RBC population has not yet recovered = haemodilution Thereafter [Hb] slowly recovers Up to 6 weeks for full recovery (as RBC are replaced) Blood has reduced oxygen-carrying capacity esp. in the first 24 hours; effect of this is somewhat ameliorated by reduced blood viscosity which favours tissue perfusion. Other responses to haemorrhage ­ ventilation ( blood flow through carotid bodies + acidosis due to tissue underperfusion) ­ platelet count* (platelets stored in spleen) ­ fibrinogen* occurs in minutes, but after  coagulation time* all clotting factors are reduced as they are consumed by activation of clotting  white blood cell count (neutrophils) in 2 - 5 hours - “Priming” for ALI/ARDS ALI = acute lung injury ARDS = acute respiratory distress syndrome * William Hewson (1770) “the blood which issued last (from a slaughtered animal) coagulated first” Non-Progressive shock Non-progressive shock - shock that gets better without treatment; fit young person loss < ~20% blood volume (e.g. donating blood ≈ 10%) Haemorrhage 100 Cardiac output (% initial) 75 blood volume and cardiac 50 output restored in 16-24 hrs 25 0 0 30 60 90 120 Minutes after start of haemorrhage Progressive and refractory shock Where blood loss