Shock is a syndrome, in which oxygen supply to various tissues and organs of the body are interrupted.1 It represents the final common pathway, of a variety of potentially lethal diseases and conditions.2,3 It is a medical emergency, involving acute tissue hypoperfusion and cellular destruction, and will ultimately lead to organ failure and death, if left untreated.
2,3 Despite a huge amount of research into understanding the syndrome, it remains a very common clinical condition, carrying high morbidity and mortality rates.2 This essay reviews different causes and types of shock, and illustrates the pathophysiological mechanisms underlying the condition, using shock caused by heart failure as an example. It also touches on the hyperlactaemia and the raised central venous pressure (CVP) associated with shock.
2) Pathophysiology of shock
Circulatory shock is defined as the failure of circulatory system to provide adequate perfusion of oxygen to peripheral tissues and organs of the body. It can be caused by a reduction in blood flow (hypovolemic shock), cardiac pump failure (cardiogenic shock), an obstruction to the circulatory system (obstructive shock), or a fall in peripheral resistance, due to excessive vasodilation (distributive shock). Each type begins with either a reduced cardiac output (CO) or a reduced venous return, with the exception of distributive shock (fig. 1).4-6
2.1 Cardiogenic Shock- occurs when the heart fails to pump effectively to meet the oxygen demand of the body, resulting in a fall in CO, and consequently, a fall in systemic arterial blood pressure. There are many causes that can give rise to this type of shock such as cardiac dysrhythmia, valvular damage, and cardiac surgery but myocardial infarction particularly with left ventricular failure remains the most common cause of cardiogenic shock.5-7 2.2 Hypovolemic Shock- is characterised by a fall in the circulating blood volume, which leads to a reduction in venous return to the heart.
Two common causes are severe GI bleeding disorder and penetrating trauma, both resulting in external haemorrhage.8
2.3 Obstructive Shock- occurs when there is mechanical obstruction to blood flow to the heart, preventing sufficient diastolic filling of the ventricles. This leads to a reduction in CO and an increase in systemic vascular resistance. Cardiac tamponade is a common cause, where there is a rapid accumulation of fluid in the pericardial space. Other causes include pulmonary embolism and pneumothorax.5,8
2.4 Distributive Shock- represents a low peripheral resistance state, associated with a loss in vascular tone, and the shift of blood away from the heart and the central circulation.5,6 Despite the fact that cardiac output may be normal or even elevated in this type of shock, hypoperfusion to end organs can still occur because of an increase in the vascular capacity so that the normal volume of blood is unable to fill the circulatory system.
5 Fundamentally, the two main causes of loss in blood vessel tone are: excessive vasodilator substances and loss of sympathetic nervous outflow supplying the vessels.5 Distributive shock can further be divided into three different categories: neurogenic shock, septic shock, and anaphylactic shock, which are beyond the scope of this essay.5,6
3. Final Common Pathway
As discussed above, shock is usually caused by diminished CO, due to factors that directly reduce venous return, or due to abnormalities to the heart itself. However, the two factors do not apply to distributive shock, a type of circulatory shock that occurs without a decrease CO. Whatever the initial cause of circulatory shock is, all types of shock lead to tissue hypoxia.
3,5 Based on different degrees of severity, circulatory shock can classically be described in three stages:10 1. Compensated stage – compensatory mechanisms lead to recovery of the circulatory system without any aid of therapy 2. Progressive stage – without any help of therapy, damages become more severe, and the compensatory mechanisms can no longer serve to protect the organs 3. Irreversible stage – shock has progressed to a stage, where no treatment will lead to any improvement. Inevitably, death will result.10,11
3) Shock Caused by Heart Failure – Cardiogenic Shock
Heart failure describes the ineffectiveness of the heart in pumping blood around to sufficiently meet the body’s metabolic demands.5 Any conditions that alter heart functions can give rise to heart failure, with the most common causes mentioned above under cardiogenic shock. CO is essentially controlled by three components: preload, afterload, and myocardial contractility. How these come into play when the heart fails, can by illustrated using the Frank-Starling curve.12
3.1 Compensated Stage
Various compensatory mechanisms will attempt to correct the reduced CO during acute heart failure. Initially, when CO falls, the body responds immediately by stimulating the sympathetic nervous system (SNS) and the renin-angiotensin system (RAS). These two mechanisms occur rapidly within the matter of minutes to hours after the heart fails (fig. 2).5,10,13
The activation of the SNS increases the level of epinephrine and norepinephrine. These neurotransmitters act on the α receptors to cause vasoconstriction, and on the β1 receptors to cause an increased in heart rate and force of contraction of the heart. Generalised vasoconstriction increases total peripheral resistance (TPR), therefore venous return to the heart increases. Consequently, arterial blood pressure and CO will be maintained or even increased, and ensure adequate tissue perfusion.5,10,13
RAS works in conjunction with the sympathetic reflex mechanisms to maintain adequate CO and arterial blood pressure. SNS activation also affects the kidneys’ afferent arterioles, leading a fall in glomerular filtration rate, thus stimulating renin secretion. An increase in renin generates more Angiotensin II, which in turn stimulates aldosterone synthesis.
Aldosterone has the potassium excreting and sodium retaining effects at the distal portions of the juxtaglomerular apparatus. As a result, water is reabsorbed osmotically following the sodium retained, therefore the venous return (preload) to the heart will be increased, which will consequently raise the CO, through the Frank-Starling (length-tension) mechanism.4,5,10,13
The Frank-Starling mechanism describes the ability of the heart to change its force of contraction, whereby the heart’s stroke volume increases with an rise in end-diastolic volume (preload). Preload is the ability of the cardiac myocytes to stretch in diastole, so with more volume, the myocyte stretching increases the sarcomere length, which leads to a greater force generated. This mechanism provides the basis, for the compensatory mechanisms mentioned above, and leads to an increase in CO (fig. 3).4,5,10,13,14
3.2 Progressive Stage
This stage of shock is characterised by various positive feedbacks, which causes vicious cycles further contributing to the overall cardiovascular decline. The following feedbacks are a few to mention among many that play a part in the progressive stage leading to the irreversible stage.10
The most significant feature of shock in this stage is the progressive deterioration of heart function. In the initial stages of shock, this feature is not very important as the heart has a huge cardiac reserve, and is able to pump 300-400% more blood than normally required, if necessary.10 However, compensatory mechanisms will eventually increase the workload of the heart by increasing contractility and preload, which in turn increases the myocardial oxygen requirement. In the long-run, cardiac output diminishes, which is known as ‘decompensated heart failure.’
Intense vasoconstriction, which also occurs during progressive shock, represents an increased afterload. This adds to the workload of the heart, and causes a decrease in tissue perfusion and impaired cellular metabolism. Accordingly, the heart progressively fails and cannot maintain adequate CO. All types of shock can eventually end in heart failure as a result of prolonged compensation (fig.4).5,10,13
Another positive feedback is the central vasomotor failure. In the initial
stages of shock, the SNS helps to maintain the distribution of cardiac output and the arterial pressure by controlling various vascular reflexes. Unfortunately, if shock becomes severe enough, to a point where cerebral blood flow is compromised, the vasomotor centre in the brain may become depressed, to the stage where the sympathetic mechanisms cease to work.10
In severe shock, hypoperfusion will lead to a generalised deterioration of many organ systems, as nutrients to these organs are depleted. At the cellular level, an example of the damages that occur in the body cells include the failure of the Na+/K+ pump, leading to an accumulation of sodium and chloride inside the cells, and potassium leaving the cells. As a result cells begin to swell up. Another damage that occurs is the release of intracellular hydrolases as the lysosomes break up, and these cause further intracellular destruction, leading to cell death.
As the liver has a high metabolic rate, its functions are especially affected due to their high reliance on oxygen and nutrients. The functions of many vital organs, such as the heart, the lungs, and the kidneys are also disturbed.10 This gives rise to a condition known as ‘multiple organ dysfunction syndrome’ which is an umbrella term describing the progressive dysfunction of many organ systems.13
3.3 Irreversible stage
At this stage, shock has become so severe that any therapy will not lead to recovery. Sometimes, cardiac output and blood pressure may return to normal, but only last for a few minutes, after which the circulatory system continues to deteriorate until death. Too much tissue damage has occurred, and destructive enzymes have been released excessively, to the extent that any recovery is impossible.10
Essentially, the factors that determine the prognosis are the processes that happen at the cellular level as the condition progresses. All types of shock lead to tissue hypoperfusion, if they become severe enough, and this
means that the cells are not receiving adequate amount of oxygen to carry out their metabolic processes. Due to lack of oxygen the cells switch from the more efficient aerobic glycolysis to the less efficient anaerobic glycolysis as their method of producing ATP. This principle explains why many cellular processes (including the ones mentioned in the previous section) fail.13,15
Under aerobic conditions, where oxygen is widely available, pyruvate molecules produced from the glycolysis pathway, enter the aerobic pathway in the mitochondria, where a net of 36 ATP molecules are produced per one glucose molecule. However, when there is lack of oxygen, the pyruvate molecules are converted into lactic acid instead in a reaction where only 2 ATP molecules are generated, which explains energy failure during shock. With a high rate of anaerobic glycolysis occurring, this causes hyperlactaemia. Thus, the amount of lactate in the body can be used as an indicator of energy failure in critically ill patients.16-18
In order to avoid lactate accumulation, the body gets rid of it mainly via gluconeogenesis within the Cori cycle, which happens predominantly in the liver. It is this balance between the rate of lactate synthesis, and lactate metabolism, which determines whether a patient presents with hyperlactaemia or not. Lactic acidosis (metabolic acidosis with hyperlactaemia) is present if the blood pH is less than 7.35, and has a lactate concentration of more than 5 mmol/L.15 If the liver fails in severe shock, gluconeogenesis cannot occur. As a result, lactate builds up even more.
Another important way of lactate elimination is via excretion through the kidneys. Therefore, measuring the level of body lactate is a very common way of assessing the extent of shock, as high levels may be an alarm for an emergency, and may indicate a high risk of developing multiorgan failure.15
Shock is the most common cause of lactic acidosis, but relying on the lactate solely as a diagnostic tool would be inappropriate, as there are many other causes of hyperlactaemia, for example, gas diffusion impairment or liver disease.15 Also, if the well-functioning organs are effectively eliminating lactic acid, the problem could be masked, where there is a localised tissue
hypoperfusion, despite a normal blood lactate.16
Furthermore, a hypothesis has been made suggesting that well-oxygenated tissues can produce lactate through aerobic glycolysis, secondary to the stimulation of Na+/K+ ATPase, as opposed to anaerobic glycolysis due to tissue hypoxia (fig.5). Therefore, lactate is a poor indicator of hypoperfusion, and hyperlactatemia may persist, even though traditional indicators such as blood pressure and cardiac output have returned to normal. However, this concept is still a hypothesis, which is yet to be tested.19
5) Raised Central Venous Pressure (CVP)
The CVP is a valuable tool in the assessment of a shocked patient, and changes in its value vary considerably, depending on the type of shock. It is defined as the blood pressure within the great veins that return blood to the right atrium.20 Either the venous tone or the blood volume determines CVP. For example, loss of blood volume or decreased venous tone will lower CVP, given that the other factor remains the same. If the blood volume decreases and the venous tone increases, the blood volume may not change. CVP is directly linked to the cardiac output, as it determines the preload.21
In cardiogenic shock, compensatory responses, which include the sympathetic reflexes, and the renin-angiotensin system, lead to fluid retention and vasoconstriction, therefore increasing the systemic vascular resistance. This could lead to a decline in the circulatory function, as it represents an increased afterload that provides resistance to the cardiac output.
Due to extra blood that is not being pumped away from the heart, blood returning to the heart adds to this end-systolic volume, and thus the preload increases. This causes a backpressure on the venous system, which is reflected as an elevation in CVP. The same principle applies to obstructive shock, where a rise in CVP occurs, as a result an obstruction to the blood flow in the circulation.5
In hypovolemic shock, despite the actions of the compensatory mechanisms,
blood pressure still decreases, as they are not powerful enough to compensate for the loss in blood volume. Subsequently, venous return to heart decreases, and so does the CVP.5
Shock is a syndrome, which describes the state of hypoperfusion. For clinicians, it represents an emergency requiring rapid intervention. The earlier the diagnosis is made, the better the prognosis. Therefore, the ability to recognise the first signs of shock is a crucial clinical skill. It is important to ensure that shock does not reach an irreversible state, because by this time excessive tissue damage would have already occurred, that death remains the only outcome.
Cardiogenic shock is used in this essay as an example to explain the pathophysiology of shock, but no matter what the causes are, it is important to highlight that all types of shock lead to cellular hypoperfusion. In mild forms of shock, compensation can deal with hypoperfusion, but once the severity of shock reaches a critical stage, vicious cycles kick in, where our very own compensatory mechanisms may eventually kill us.