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Lethal triad of death- the extreme and irreversible loss of homeostasis

Have you ever heard of the condition called the lethal triad of death? This complex change in homeostasis will be discussed in a simplified tone in this article.


What is the lethal triad of death?


A medical condition involving, hypothermia, coagulopathy and acidosis. Each of these factors can compound the other leading to a chain reaction increasing the mortality rate in a so called positive feedback.

As you may or may not know, the body is regulating its internal environment by a complex control mechanism known as the negative feedback loop. Thus, the positive feedback loop is the opposite, instead of bringing a rising factor back to normal the stimulus progressively increase the response to as long as the stimulus is continued, leading to a progressively amplified response.


This condition is seen often in trauma patients. When the body loses a lot of blood a hypoperfusion can lead to failed body temperature control. As it falls below 35 degrees we call it hypothermia. The failed body temperature control is an example of a failed negative feedback as the response initiated by the stimulus failed to bring the body temperature back to normal.


As to explain this a little bit better since it is an important point to understand when talking about the lethal triad of death. When the body loses a lot of blood the blood circulation naturally decreases, and this is known as hypoperfusion, the reduced amount of blood flow. As the blood flow progressively decreases the circulation of heat also goes with it, now we have progressed in to the state of hypothermia. The body responds to the loss of blood circulation by pumping out more blood faster by increasing the heart rate, as a way to try and increase the circulation again. But what happens to a patient with a hemorrhage which caused this mess from the start? The patient will, unless the hemorrhage is stopped, bleed out because of the response. And the more blood is lost the more response is initiated.

And this is known as a positive feedback loop initiated as the negative feedback fails.


What causes the lethal triad of death?


This will be described step by step:

  1. Hypothermia- causes a decreased cardiac output as well as a decreased response to catecholamine, a neurotransmitter regulating physiological function such as heart rate and breathing. In order for the body to prevent losing more heat the vessels goes into vasoconstriction. As a result of vasoconstriction the body gets an impaired tissue oxygenation.

  2. Coagulopathy- Hypothermia causes a platelet dysfunction. When the core body temperature drops below 37°C, platelets become more susceptible to activation by thrombotic stimuli. Inappropriate fibrinolysis is activated meaning an enzymatic breakdown of fibrin in blood clots. Hypothermia also deteriorates coagulation as clotting factors are highly sensitive to temperature changes. As the patient continues to haemorrhage more platelets and clotting factors are lost.

  3. Acidosis -Our body’s pH is related to the number of hydrogen ions in the blood and is controlled by both the pulmonary and the renal system. Normal blood has a pH between 7.35 and 7.45. A patient may be considered acidotic when the pH falls below 7.35. When a patient becomes acidotic it basically means that the demand for oxygen is high but the supply is low. As the patient continues to hemorrhage the continuation of loss of erythrocytes will lead to anaemia. Thus we are now back at the previous problem, coagulopathy. Coagulation is very pH dependent, as ph falls, coagulation is disrupted. A fall from 7.4 to 7.0 can result in a coagulation decrease of up to 70%. And as the patient is hypothermic, the disturbed oxygen balance cannot be fixed since hypothermia causes vasoconstriction as well as a decreased cardiac output.


  1. Hypothermia causes:

  2. Vasoconstriction causes:

  3. Decreased transport of oxygen which causes:

  4. Worsening of acidosis which in turn:

  5. Worsen the coagulopathy

And then we're back to where we started.


During these circumstances the metabolism moves from aerobic to anaerobic mechanism with lactic acid being one of the by products. Perfusion then decreases and lactic acid accumulates in the tissues which lowers the pH even more and worsening the acidosis.


Is it now easier to connect the dots? One condition leads to another and causes a positive feedback loop. Once you get it, you’ll realize this response mechanism is really awesome and cool, it makes you wanna read into it more and more.



/Milla

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