Introduction

Blood volume in the textbook subject is of the order of 5 L (see Chapter 1) and at any one time about 65% of this volume is in the venous compartment of the circulation. A reduction in blood volume may occur in many ways. Loss of whole blood through blood vessel trauma either directly out of the subject or into other tissues such as the lumen of the stomach or a thigh muscle is referred to as haemorrhage. However, excessive vasodilatation of peripheral blood vessels will induce similar physiological responses to loss of blood volume. These processes increase the ‘volume’ of the circulatory system whilst the volume of blood it contains remains unchanged leading to a relative hypovolaemia.

Normal physiological compensatory responses will usually cope with low levels of blood loss (up to 10% blood volume) without problem. This happens frequently on a voluntary basis with people who lose 500 mL blood while attending a blood donor session. The fundamentals of these physiological responses are firstly short-term maintenance of arterial blood pressure so that tissue perfusion is sustained and, secondly, over a longer time course, the lost blood volume is replaced. These mechanisms, which link together many of the individual topics covered in greater detail earlier in this book, will now be reviewed. Severe insults to the circulatory system lead to the syndrome of circulatory shock. This topic is discussed at the end of this chapter. A case history of a patient who has suffered a haemorrhage is shown in Case 14.1:1.

Arterial blood pressure changes in response to haemorrhage

Rapid (time course in minutes) blood volume losses of the order of 5–10% in someone with normally functioning circulatory reflexes produce little if any change in mean arterial pressure. A rapid 15–20% haemorrhage will cause a modest reduction in mean arterial pressure from a normal textbook value of about 93 mm Hg (see Chapter 9) to about 80–90 mm Hg. Recovery from such a haemorrhage using normal physiological mechanisms should be uneventful. A 20–30% blood volume loss might typically result in a drop in mean arterial blood pressure to 60–80 mm Hg and generate some indications of shock responses but such a haemorrhage would not normally be fatal. A blood volume loss of 30–40% however would lead to a substantial reduction of mean arterial blood pressure to 50–70 mm Hg with serious shock responses which may become irreversible. Blood volume loss beyond 50% would normally be fatal.

The fundamental links between blood loss and hypotension are described in Chapter 4 and are summarized in Figure 14.1. Decreased blood volume leads to decreased right atrial pressure and consequently decreased filling of the right ventricle. This leads to a decrease in stroke volume (Starling’s law) and therefore to a reduction in cardiac output. A 20% reduction in blood volume would typically result in an initial reduction in resting cardiac output from about 5 L/min to about 3 L/min. As mean arterial pressure is the product of cardiac output and peripheral resistance there is a fall in blood pressure as identified above. An important first aid point is that it is inadvisable to prop up someone who has suffered a haemorrhage to a sitting position. This would only further reduce the preload effects on the heart.

The compensatory responses which would help to restore blood pressure are triggered by the cardiovascular reflexes discussed in Chapter 10. Of prime importance is the carotid sinus baroreceptor reflex. The modified nerve endings which constitute the baroreceptor become less stretched as blood pressure falls. Fewer action potentials will therefore pass up the glossopharyngeal nerve and enter the brain at the level of the medulla. Following central processing of the baroreceptor input there will be activation of sympathetic outflow and inhibition of the parasympathetic nerve supply to the heart. The consequences are an increased heart rate (tachycardia) and an increase in cardiac contractility, both of which contribute to a raised cardiac output despite decreased preload effects on the heart (see Chapter 4). Re-establishment of a normal resting stroke volume as a result of a sympathetically induced increase in cardiac contractility is illustrated in Figure 14.2. In otherwise normal subjects, a significant tachycardia does not occur until the blood loss has exceeded 700–800 mL (10–15%).

Sympathetic nervous system activation also leads toα-receptor-mediated vasoconstriction (see Chapter 9). The regions of the circulation which are particularly affected by sympathetic vasoconstriction responses include the skin, gut, kidney and skeletal muscle. The brain and coronary circulations are relatively preserved especially during the sequel to a haemorrhage amounting to about 20% or less blood volume loss. Concurrent sympathetically mediated venoconstriction will help to maintain central venous pressure and hence limit the fall in preload on the right side of the heart. An unfortunate practical aspect of this venoconstriction is that it may hinder attempts to gain access to the circulation with a venous cannula so that infusion of blood or other replacement body fluids can commence.

The patient who has suffered a haemorrhage and has therefore activated these compensatory responses appears pallid due to cutaneous vasoconstriction, with cold clammy skin, possibly with peripheral cyanosis, and a weak rapid pulse. The responses to haemorrhage will vary considerably between individuals depending on factors such as age and gender, nutrition and fluid balance, season of the year and environmental temperature as well as less easily defined individual characteristics. The extent and speed of the haemorrhage will be important as well. When haemorrhage reaches levels of the order of 25–35% blood loss the sympathetic activation outlined above is succeeded by inhibition of sympathetic outflow and progression to circulatory shock as described later in this chapter. Peripheral cyanosis (see Chapter 1) is associated with a reduced local blood flow and hence greater than normal extraction of oxygen from the remaining blood. Sweating is regulated by the sympathetic nervous system and so is another manifestation of the baroreceptor reflex. Some of these autonomic nervous system mediated changes feature in the case history of Linda Hamilton outlined in Case 14.1:1. A simple but quite effective test of peripheral circulatory function is the nail capillary refill test. Pressure is applied to a finger nail bed until it has blanched. This indicates that blood has been forced away from the area. When pressure is removed the time taken for blood to return to the nail bed (indicated by a change in colour) is measured. Normally capillary refill time will be less than 2 seconds. A longer time indicates reduced tissue perfusion. This test is particularly useful in children as other signs of imminent circulatory collapse appear relatively late.

Short-term responses which help to restore lost blood volume

In Chapter 11 the ‘Starling forces’ which determine the movement of water across capillary walls are described. Fundamentally, the capillary blood pressure (hydrostatic pressure) tends to move water out of the capillary bed into the interstitial fluid. This is opposed by a gradient of colloid osmotic pressure which will tend to draw water from the interstitial compartment back into the capillary.

Following a haemorrhage, there may be a fall in mean arterial pressure but, in addition, a compensatory peripheral vasoconstrictor response occurs. As the main resistance vessels (see Chapter 9) are the arterioles, vessels which come immediately before the capillaries, there will be a fall in capillary blood pressure following a haemorrhage. This will alter the balance of the Starling forces and, as the colloid osmotic pressure of plasma is initially unchanged, this will result in a net movement of water from the interstitial space into the blood. This is illustrated in Figure 14.3. The rate and extent of this internal replacement of lost blood volume will depend on the rate and degree of blood loss. A rapid loss of 20% of blood volume (about a 1000 mL haemorrhage in the ‘textbook person’) will lead to perhaps 600 mL of interstitial fluid entering the blood over a period of around 10 minutes. This is sometimes referred to as an ‘internal transfusion’. As skeletal muscle constitutes about 50% of body weight this tissue is a major source of the interstitial fluid for the internal transfusion.

A further factor which helps to maintain the internal transfusion is hormonally driven glycogen breakdown in the liver (Fig. 14.3). Sympathetic activation and an associated increase in adrenaline (epinephrine) secretion from the adrenal medulla lead to release of glucose from glycogen stores and, as a consequence, an increase in plasma and interstitial fluid osmolarity. More than half of total body water is held inside cells (see Chapter 11) and the rise in osmolarity draws fluid into the interstitial space from the intracellular compartment. It has been estimated that this fluid movement from the intracellular compartment contributes about half of the volume of the internal transfusion.

The colloid osmotic pressure of plasma will gradually fall as a result of dilution with interstitial fluid. At the same time, capillary blood pressure will gradually rise back towards normal levels as a result of the internal transfusion. Eventually a new equilibrium will be established between the Starling forces and so the internal transfusion will cease.

A consequence of the internal transfusion is haemodilution, a fall in haematocrit. Many patients who have suffered a haemorrhage will already have a low haematocrit by the time they reach hospital. While on the one hand this reduced haematocrit will lower blood viscosity (see Chapter 8) and make it easier for blood to flow round the body, the reduced viscosity also lowers the resistance to blood flow and potentially contributes to a further fall in blood pressure. The reduced oxygen carrying capacity of blood as a result of haemodilution will restrict oxygen delivery to already poorly perfused tissues.

Longer term responses which help to restore lost blood volume and electrolytes

Shifting water between the various fluid compartments in the body as a short-term measure still leaves the problem of replacing the overall water loss following a haemorrhage. This is achieved by a combination of changes in glomerular filtration rate in the kidneys and hormonally mediated changes in kidney tubular function (Fig. 14.4). Assuming an adequate oral salt and water intake, in the case of a 20% blood volume loss the body fluid volumes would be returned to normal over a period of about 3 days.

Sympathetic activation, as a result of the fall in blood pressure and the baroreceptor reflex, leads to intrarenal vasoconstriction. This particularly affects the afferent arterioles but also the efferent arterioles at the glomeruli. This leads to a reduction in glomerular filtration rate which helps to conserve water and electrolytes. The potential danger of prolonged intrarenal vasoconstriction is ischaemia leading to acute tubular necrosis (ATN). The nephron becomes blocked with swollen and necrotic tubular epithelial cells and the patient becomes oliguric (less than 100 mL urine per day). ATN is recoverable provided volume replacement is achieved and glomerular function is re-established within an adequate time course.

The main hormones involved in salt and water retention are described below.

Decompensated or irreversible shock following haemorrhage

The events described above constitute the compensatory responses to haemorrhage. Most normal people can recover from the loss of up to about 25% of blood volume by purely physiological responses, although clinical intervention will accelerate recovery and minimize end-organ damage. If the blood loss exceeds about 30% of total blood volume and there is a delay of more than 3–4 hours before volume replacement therapy commences, the patient may enter the syndrome of decompensated or irreversible shock. Subsequent full restoration of blood volume may be to no avail.

An increase in sympathetic nervous system activity helping in various ways to sustain arterial blood pressure as described above is a key feature of the compensatory responses to haemorrhage. Decompensation is associated with a fall in arterial blood pressure as a consequence of substantial peripheral vasodilatation. This follows a reduction in sympathetic vasoconstrictor activity which originates in the central pathways in the brain which control sympathetic outflow. Circulating levels of vasoconstrictor hormones such as Ang II, vasopressin and catecholamines remain high but are unable to counter the fall in sympathetic activity. This phase is associated with bradycardia.

The decline in blood pressure has an adverse effect on cardiac function with reduced coronary perfusion. This results in a dangerous positive feedback loop as the fall in cardiac output will lead to further reduction in blood pressure and therefore further impaired coronary blood flow and hence further reduced cardiac performance. The poor tissue perfusion also has an adverse effect in peripheral tissues as it leads to local metabolic acidosis. Accumulation of tissue metabolites, such as H⁺ (see Chapter 9), leads to vasodilatation and a further reduction in arterial blood pressure.

Decompensated shock represents a downward spiral of events which may be difficult to interrupt. The general principles of circulatory failure management are firstly to ensure adequate lung ventilation and provide extra oxygen, secondly to restore blood volume by infusion of blood or other fluids and thirdly to use interventions which improve cardiac performance. Experts in this area sometimes refer to the ‘golden hour’. Optimal management of haemorrhage within this window of opportunity is crucial for minimizing morbidity and mortality. Correct recognition of the signs and symptoms of reversible shock helps to avoid the onset of catastrophic circulatory collapse.

Causes of shock

Physiological shock is the failure to provide end organs with adequate nutrients. Shock can be conveniently considered under four main headings:

In each case tissue perfusion is reduced and there is an inadequate supply of oxygen to the tissues.

Changes in the body which follow a haemorrhage (hypovolaemic shock) have been outlined above. It should be stressed that there is considerable variation in the responses between different individuals. The prognosis for individuals who suffered identical haemorrhages may be quite different.

In cardiogenic shock following events such as myocardial infarction (see Chapter 5) or serious arrhythmias there will be a fall in systemic arterial blood pressure as a result of the fall in cardiac output. In contrast to hypovolaemic shock, central venous pressure and pulmonary vein pressure are both likely to be increased. Poor left ventricular performance will lead to a rise in filling pressure on the left side of the heart and the possibility of pulmonary oedema. Fluid replacement therapy must therefore be very carefully managed. The changes in kidney function, which are primarily triggered by the fall in arterial blood pressure, will be broadly similar in haemorrhagic and cardiogenic shock.

Septic shock is a common cause of distributive shock and may be associated with bacterial, viral, fungal or protozoal infections. These infections may lead to the release of a wide range of toxic mediators which cause cell damage and cell death. Septic shock represents a complex series of events which may be collectively referred to as the systemic inflammatory response syndrome (SIRS). In the initial phases of septic shock, there is peripheral vasodilatation and a high cardiac output with excess peripheral perfusion and adequate urine flow rate. Later stages of septic shock are associated with vasoconstriction and a fall in cardiac output as a result of increased production of vasoconstrictor agents such as Ang II, catecholamines and thromboxanes. Treatment of the infection is a crucial part of management strategies.

Anaphylactic shock is another form of distributive shock. It represents an immediate hypersensitivity reaction which usually occurs within 30 minutes of exposure to an antigen such as a drug (e.g. penicillin), a specific protein (e.g. in a peanut) or an insect venom (e.g. a bee sting). It is mediated by immunoglobulin E (IgE) and leads to the release of mediators such as histamine which are stored in granules within mast cells. Vasodilatation and an increase in capillary permeability follow the release of histamine (see Chapter 11).

Fluid replacement therapy

The primary reason for fluid replacement therapy is to maintain tissue perfusion by ensuring an adequate cardiac output and a sufficiently high arterial blood pressure. Optimizing the preload effects on the heart in order to maintain cardiac output is an important aspect of fluid management. However care must be taken to avoid overload as this may lead to pulmonary oedema, especially if the patient is already in cardiac failure (see Chapter 6).

An extensive clinical analysis of fluid replacement therapy in a wide range of clinical conditions is outside the scope of this book but some general principles can be established. In relation to calculating the quantity of replacement body fluid the following points are relevant:

Further reading