This chapter is relevant to Section I1(i) of the 2017 CICM Primary Syllabus, which expects the exam candidates to "explain the distribution and movement of body fluids". In this specific scenario, the movement of the body fluids is out of the body. It has come up a couple of times, as the college has asked direct questions about "what happens when you lose X amount of blood?", specifically in Question 2 from the second paper of 2009, and Question 11(p2) from the first paper of 2008.
Weirdly there is no specific category for this in the syllabus. Fortunately, there's plenty of non-specific categories, and they cover the area in substantial granularity. Section G6(i) talks about "the response of the circulation to ...haemorrhage", and those are lovingly detailed in the chapter on the cardiovascular response to haemorrhage and hypovolaemia. The effects of the loss of actual haemoglobin is mentioned in cardiovascular response to isovolaemic anaemia, and the haematopoietic recovery from blood loss is discussed in the chapter dealing with the production of red blood cells.
- Staging of blood loss is in terms of % of circulating volume lost:
- Four classes (ATLS): <15% of volume, 15–30%, 30–40% and > 40%
- Loss of 1000ml of blood (20% of the total circulating volume) in a 70kg subject represents most of the stressed volume.
- Loss of 2000ml of blood = 40% of the circulating volume = severe haemorrhagic shock
- Hypovolemia and cardiovascular compensation
- Baroreflex activation and chemoreceptor activation.
- Decreased vagal stimulus; thus increased heart rate
- Sympathetic activation, which has multiple effects:
- Increased peripheral vascular resistanc
- Redistribution of blood flow away from the cutaneous and splanchnic circulation
- Stimulation of systemic catecholamine release from adrenal glands, which produces an increased systemic effect in addition to the peripheral sympathetic nervous system effecs
- Stimulation of vasopressin release via the projections from the nucleus of the solitary tract to the hypothalamus
- Stimulation of renin release by sympathetic stimulation of the juxtaglomerular cells, and due to lower renal perfusion
- Transcapillary fluid redistribution and isovolaemic anaemia
- Vasoconstriction of arterioles results in reduced capillary hydrostatic pressure
- This results in a change in the Starling relationship in the microcirculation
- The result is a movement of free water out of the interstitial space and into the intravascular space
- This dilutes the blood volume and decreases the haematocrit, decreasing the haemoglobin concentration of the blood, but restoring some of the circulating volume
- Renal fluid/electrolyte conservation and haemopoiesis
- Renin secretion causes:
- Vasoconstriction (by angiotensin)
- Increased sodium retention (by aldosterone)
- Vasopressin release causes:
- Vasoconstriction (by V1 receptors)
- Increased water retention (by V2 receptors)
- Venous hypotension decreases atrial natriuretic peptide secretion,
- Decreased renal blood flow
- Decreased urinary water and sodium excretion
- The net effect is decreased urine output and increased retention of sodium and water
- Erythropoiesis is stimulated by EPO release from the kidney, stimulated by decreased oxygen delivery
In Question 2 from the second paper of 2009, the college supplied the candidates with a patient weight. From this, they were expected to deduce that the staging of shock was a part of the marking criteria. "When a weight and a volume are supplied it is expected the percentage blood loss would be calculated and the shock graded or the haemorrhage at least described as severe", the examiners complained when some of the trainees were unable to read their minds. The classification of haemorrhagic shock they were probably referring to is the ATLS system from the American College of Surgeons:
You can read more about the validity of this system in Guly et al (2011). In short, it appears that one does not score marks here unless one explicitly states that the loss of 40% of one's circulating volume is "severe haemorrhage", presumably because to omit this would mean that one does not recognise the situation as being particularly serious.
The response to haemorrhage seems to take 3 stages, which are indistinct and with significant overlap:
The immediate changes relate to the loss of circulating volume. The removed fluid is whole blood; what remains behind is also whole blood; provided the haemorrhage occurred rapidly, there has been no time for the composition of the intravascular fluid to change, and if one were to take a sample of the intravascular blood, one would not detect any changes. The haematocrit and the concentration of electrolytes will not be altered at this early stage, as the compartments have not yet had a chance to equilibrate.
The osmolality of the remaining fluid (that’s 2800ml of plasma fluid left behind, or 4000ml of whole blood) has not yet changed. Osmoreceptors are ignorant of the volume reduction. However, vasopressin release is triggered anyway, by baroreceptors sensing a loss of blood pressure.
The topic of cardiovascular response to haemorrhage is sufficiently interesting that an entire chapter has been dedicated to discussing it in the cardiovascular section. Here, the following brief summary will suffice:
Now, let us return to examining the fluid shifts which occur in response to the loss of blood.
The restoration of blood volume occurs by transcapillary refill. This is the term given to the net movement of fluid and of protein (mainly albumin) from the interstitial compartment into the intravascular compartment. It is well described by Drucker et al in this article, the complete form of which is not available for free anywhere.
The Starling equation, which describes the net movement of fluid in the capillaries, describes transcapillary refill.
Essentially, the sympathetic response to haemorrhage results in a decrease in the diameter of the arterioles, and therefore a decrease in the pressure at the capillaries.
Oncotic pressure remains the same as it was before the haemorrhage (remember, the fluid composition of the intravascular compartment is unchanged). However, it is no longer balanced by high capillary hydrostatic pressure. The result is a movement of free water out of the interstitial space and into the intravascular space.
This dilutes the capillary fluid, and the process comes to a rest when the capillary fluid is so diluted that the hydrostatic attraction into the capillary is balanced by the osmotic (oncotic) attraction out of the capillary.
The next stage of these fluid shifts is the movement of interstitial albumin into the intravascular compartment. This movement is probably unrelated to the Starling forces, because by all rights the albumin should stay put. It may be mediated by a protein concentration gradient, and appears to be related to the volume of the interstitial compartment, and the pressure in it. In any case, it seems that interstitial albumin replenishes the intravascular albumin deficit. Not only that, but haemorrhage stimulates albumin synthesis by the liver (for this very reason).
The vast majority. A study performed on hemorrhaging dogs has revealed that the rate of transcapillary refill does not seem to be related to arterial pressure, cardiac output or systemic resistance. Rather, it is a function of the severity of the haemorrhage. At the terminal stages of shock in the aforementioned dogs, transcapillary refill fluid accounted for more than 75% of plasma volume. The refill rate was sufficiently high to sustain a plasma volume roughly 2/3rds of the initial plasma volume, irrespective of the rate of bleeding.
Another study from 2010 repeats this dog experiment with a few methodological differences. Their article is accessible for free, and there are graphs which demonstrate roughly how much refill one can expect in uncontrolled haemorrhage, and how fast.
After bleeding for 30 minutes, there was around 20ml/kg of transcapillary fluid in the circulation (which is generally held to be 70ml/kg) – another words, after half an hour of bleeding the blood volume is already diluted and contains about 30% interstitial fluid. These numbers are consistent with the gospel of St. Brandis; the chapter on rapid blood loss reports that up to 1000ml of fluid per hour is restored to the intravascular compartment in this fashion.
This has implications for the man with the syringe. Yes its true that immediately after the loss of a large volume of blood one will not record a difference in haemoglobin concentration. However, at half an hour post haemorrhage, you can already see a haemoglobin drop. The loss of blood pressure associated with volume loss also activates the renin-angiotensin-aldosterone system, the net effect of which is the conservation of sodium and water.
Thus. transcapillary refill has all but replenished our intravascular compartment. The repletion is incomplete- not all of the volume compensation was required, as venous tone and sympathetic tone have also increased, and these other compensatory measures will ultimately increase the capillary hydrostatic pressure to a point where transcapillary fluid migration can no longer occur.
The fluid which has migrated out of the interstitial space is in composition essentially the same as the fluid in the intravascular space. Electrolyte concentration at this stage is not meaningfully altered in this simple model. In a real person, there may be changes to the concentration of bicarbonate as the acid-base balance is disturbed by rising lactate in the poorly perfused tissues; additionally the increase in ADH will result in the retention of free water, and therefore some dilution of the electrolytes will occur.
The interstitial fluid deficit is replaced over the period of some hours by systems which can be broadly described as the humoral defense of blood flow and volume. At a basic level, these can be summarised as hormonal processes (such as the activation of the renin-angiotensin-aldosterone system) which result in sodium retention. Because sodium is distributed into extracellular fluid, this also means the expansion of the extracellular fluid volume, which would be welcome under the circumstances. There may be some shift of water out of the intracellular compartment, but because the concentration of extracellular sodium does not change very much with haemorrhage, there is little osmotic incentive for water to move out of cells.
The haemopoietic response to haemorrhage is nearly immediate, and the bone marrow makes attempts to replenish the lost erythrocytes by ramping up production and by releasing immature reticulocyte forms into the circulation. The replacement of erythrocyte numbers can take as long as 20 days.