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Case Summary

This is the first case of the year and begins a series of problems dealing with general
physiological and biochemical processes. The case is one of an MVA in which the driver
suffers massive blood loss, and covers a wide range of issues. Because of this and the
demands of the Orientation Program in the first week, we are going to run this PBL over
two weeks. The major topic of the effects of blood loss on the body’s normal physiological
processes and the mechanisms that are available to limit and compensate for these
effects spans both weeks with other issues being covered as they arise over the progress
of the case. These issues include:

First aid and site management, trauma and triage, ABC: Students all enter with a current
senior first aid certificate, so the generalities here should be fresh in their minds, and
specific content will be merely revision. However, there are some new concepts such as
the principles of fluid replacement which will extend their knowledge of this area.

Standard precautions and blood-borne infections: This serves to introduce microbiological
concepts, as well as reinforce the practical steps in a situation which presents a risk to the
health care provider.

Duty of care and legal liability: Most groups identify these with surprising ease, right from
the first trigger. There are some detailed issues about ethical and legal duty of care,
negligence and the status of medical students, which will be addressed in resource
sessions.

Causes of accidents: The scenario makes the association between MVAs and ethanol
obvious but there are more generalised issues at stake here. Epidemiologists have a way
of thinking about accidents which treats them like any other disease process: with factors
in the subject (drugs, alcohol, skill, temperament), in the environment (divided highways,
lighting, signing, guard rails), and in the agent of injury (car design, seat belts, air bags).

As mentioned earlier, shock and its effects, particularly on the cardiovascular system, form
the main learning agenda: The topic introduces the general anatomy and organisation of
the cardiovascular system, and physiology of cardiovascular function. The specific issue
with hypovolaemic shock is to understand how reducing blood volume by haemorrhage
impairs the ability of the system to maintain blood flow to the tissues, and how the system
compensates successfully for small blood loss challenges and fails to deal with large ones.
Underlying this is the general topic of regulatory system control - "homeostasis."

As the cardiovascular system is emptied out by bleeding, pressures tend to fall. The heart
needs a certain venous pressure to enable the ventricles to fill - thus reduced blood
volume compromises the pumping action of the heart and leads to a fall in arterial blood
pressure and reduced tissue perfusion. Students without a physiological background have
trouble with the concepts of blood flow (volume per unit time) and blood pressure (force
per unit area). Pressure is measured because it is easy to do, but it is actually the flow
which matters.

Homeostatic mechanisms are triggered as the system attempts to compensate for the
reduced filling pressure. Tachycardia and peripheral pallor are compensations which help
maintain blood pressure, and therefore perfusion of vital organs, by improving the function
of the heart and shutting down flow to non-essential areas like skin, muscle and gut. The
sympathetic nervous system is an effector in this negative feedback regulatory system and
the sweating which is seen in shocked patients is an overflow effect which has no
physiological benefit - sympathetic nerve terminals stimulate sweat glands as well as
promoting vasoconstriction in the skin and generally throughout the peripheral vasculature.

A good question to challenge the students' concepts of homeostasis would be: "Which of
the signs of hypovolaemic shock are compensatory responses and which are primarily due
to reduced blood volume?" Note that tachycardia and pallor are signs of compensatory
mechanisms which tend to maintain blood pressure. Thus, in the time sequence of
changes in a bleeding patient, initially the pulse rate rises but this is followed by a fall in
blood pressure as bleeding continues and compensatory mechanisms fail.

Because of the scope of these issues, it is possible that students will feel overwhelmed
and be tempted to disengage from the learning agenda. Alternatively, they may go the
other way and over-commit in an attempt to cover all issues in depth. This is where the
role of the experienced PBL tutor comes in to play - to provide guidance with regard to
depth of learning, and reassurance that it is valid for students to start and finish at different
points according to their background.

Triggers and Tutor Notes

Tutorial 2 : Trigger 1

PRESENTATION

It is 10.30 pm on a Friday night, when two medical students see the car ahead of
them run off the road and crash into a tree. They stop and run to the scene. A young
male, covered in blood, is struggling to get out of the driver's seat of his wrecked
car. There is blood spurting from a wound in his left thigh.

"What should we do?"

Discussion Checklist

What are the critical features of this presentation?
List your hypotheses for the presentation. Explain your reasoning.
What information would help you to refine your hypotheses?
How would you answer the students’ question?

Tutor Notes

Prompts:
What are the students' obligations in this situation?
Are their legal and ethical obligations identical?
What standard of competence is expected of medical students?
What are the risks to the driver and the students?
What are the priorities at the scene of an accident?
What principles of first aid apply here?

The major issues arising from this trigger are Duty of Care, first aid and priorities in
emergencies, and standard precautions. All the students have current First Aid
certification, so they should be able to work through these without too much trouble.

Duty of Care is primarily based on the principle of non-maleficence (“first, do no harm”). It
covers issues such as patient consent, the type of relationship in which Duty of Care
applies, how it varies in different circumstances and between differently qualified
individuals (doctors / nurses / lay people), and the Good Samaritan Act.

In this situation, the medical students are in the role of Good Samaritans. What are the
implications of this? Are they legally responsible for the outcome of offering assistance at
an accident? What standards are expected of them? Are they more liable than members of
the public who have no training? Are they legally liable for NOT offering assistance when
they are trained in first aid? What is the difference between a legal and a moral
responsibility? Who determines what is a moral responsibility? Is this a normal doctor-
patient relationship? Is consent needed in an emergency?

Clearly, there is a moral and ethical obligation to render assistance in an emergency but
who determines the boundaries of that moral responsibility? What is the difference
between a legal and a moral responsibility? Is this situation a normal doctor-patient
relationship? What about consent - is consent needed in an emergency where the patient
may be unconscious or mentally clouded by injuries?

Priorities in Emergency Management:
The first priority in management of an emergency situation such as this requires that steps
be taken to prevent further injuries from other traffic. A motor vehicle should be parked
upstream of the site with its emergency flashers operating and headlights illuminating the
scene.

Whether to remove the victim from the crashed vehicle or wait for further assistance is a
judgement call depending on the circumstances, the extent of injuries and the likelihood of
further injuring the victim while moving him. There are also dangers in delay - it is more
difficult to assess injuries, maintain airway, control bleeding, etc in the vehicle. The vehicle
itself presents danger, particularly fire from leaking fuel (minimise by switching off the
ignition).

Assessment of, and assistance to, the victim starts with the familiar "A,B,C" of first aid
training. From the trigger, it appears he is losing blood rapidly but is at least conscious
enough to be trying to escape from the car.

Standard Precautions:
The bleeding raises the issue of danger to the students from blood borne infections. We
will be resourcing "standard precautions" and introductory ideas about infectious agents
during the week's classes. Hepatitis C is a particular worry for health workers - it has a
high probability of infection following needle-stick injury or contact with body fluids through
broken skin, and (unlike hep B) there is currently no vaccine.
Learning Objective Questions

What is Duty of Care? How does it apply to MVAs and similar situations?
What are the risks to the carers?
What are the priorities for assessment and treatment of the victim?
What are Standard Precautions?

Tutorial 2 : Trigger 2

FIRST AID & INITIAL EXAMINATION

The students have moved the driver, Mark B., away from the wrecked car. He is
bleeding profusely from the wound in his left thigh. One of the students manages to
control the bleeding by pressing on the open wound with his hands. Throughout,
Mark is conscious and complains of feeling thirsty and cold.

An ambulance and the police arrive soon after. On examination, he is conscious but
cloudy, groaning in pain and complaining of difficulty breathing.

Other observations are:

* systolic BP 70 mmHg (diastolic too low to measure)
* Pulse 135/min, thready
* respiratory rate 30/minute
* airway intact
* chest extensively bruised and tender, possibly multiple rib fractures
* deformity of the left thigh with substantial haemorrhage
* numerous bruises and lacerations of both lower limbs
* extreme pallor - pale face, conjunctiva and palmar creases - and cold, sweaty
extremities
* no obvious head injury, no neck pain, pupils equal and reactive to light.

Discussion Checklist

What mechanisms underlie Mark’s signs and symptoms?
Which of these findings are the most significant? Why?
How do these findings affect your list of hypotheses?
Can you prioritise them?
What immediate measures are necessary to help this man?

Tutor Notes

Prompts:
How do the signs and symptoms of shock relate to the physiological mechanisms used to
maintain BP and circulation?
We now have a picture of multiple injuries, with probable chest injury, fractured femur
(probably compound as there is a bleeding wound associated with the deformed limb), and
extensive blood loss leading to shock.

The principal concern here is shock: How is it caused? What are its clinical features and
what are the mechanisms underlying them? How does the body respond to hypovolaemia.
Groups with some background in cardiovascular physiology may be able to discuss how
the symptoms and signs of shock relate to the physiological compensating mechanisms
which are attempting maintain the cardiac output and blood pressure.

One of the major causes of shock, and the one that applies here, is loss of blood volume.
This leads to inadequate filling of the heart and results in inadequate cardiac output (flow
rate, litres per minute). Thus the arterial blood pressure falls and tissue perfusion
decreases. In other situations, shock may result from dilation of the blood vessels so that a
normal blood volume can no longer fill the system (e.g. septic shock), or catastrophic
failure of the pump action of the heart (cardiogenic shock).

Compensatory mechanisms against the fall in blood pressure involve the sympathetic
nervous system and the hormones vasopressin and angiotensin II. Generally, these tend
to increase the peripheral resistance and so increase blood pressure at the expense of
cutting down flow to the tissues. "Non-essential" vascular beds, like skin (hence the pallor)
and gut, are affected more than brain or coronary vessels. The heart rate is increased to
help maintain output despite reduced filling (cardiac output = heart rate x stroke volume).
Initially, these compensating mechanisms permit maintenance of adequate blood pressure
and perfusion of the vital organs. As the situation worsens with more and more blood loss,
the compensating mechanisms will fail, leading to reduced blood pressure, reduced tissue
perfusion and further damage to vital organs including the heart.

The American College of Surgeons uses a four-level classification of hypovolemic shock.
Class I is up to 15% blood volume loss, and has no changes in haemodynamic parameters
(heart rate and blood pressure) and no complications. Class II is 15-30% blood loss where
elevated pulse rate and reduced pulse pressure (reflecting reduced cardiac stroke volume)
are present, accompanied possibly by tachypnoea and anxiety. Urinary output is usually
still satisfactory in Class II shock, indicating that perfusion of vital organs is maintained, but
compensatory mechanisms are in evidence. Class III is 30-40% blood volume loss and is
very dangerous haemorrhage, with the classic signs of shock present: falling blood
pressure despite tachycardia, cold periphery and mental confusion reflecting falling tissue
perfusion, sweating reflecting maximal sympathetic nervous system activation, and
depressed or absent urinary output indicating compromised renal perfusion. Class IV
shock, greater than 40% loss of blood volume, is immediately life threatening, with deeply
depressed mental state score and cardiovascular collapse. The situation is only
salvageable by rapid and massive volume replacement with immediate surgical
intervention for definitive haemostasis.

There is a simple yes-no formula for detecting shock clinically: the Alghevar scheme which
compares (or takes the ratio of) the systolic blood pressure and the heart rate. This is
based on a numerical coincidence, since it is dependent on the choice of units, but with
millimetres of mercury and beats per minute, it works. Normally the systolic blood pressure
is numerically greater than the pulse rate (ratio greater than unity). Rising pulse rate in the
compensation for blood loss will take the pulse rate above the systolic BP (ratio less than
unity). As the compensatory feedback systems fail and systolic blood pressure continues
to fall, so too does this ratio.

Successful treatment depends on stopping the loss and replacing the fluid as early as
possible to limit the damage.

There is also a strong hint in this trigger about possible internal injuries from the chest
trauma. What structures could be damaged by the impact of the steering wheel? As well
as multiple rib fractures, which may lead to an unstable chest wall and ventilatory difficulty,
there is the serious possibility of trauma to the heart, great vessels, trachea, bronchi and
lungs, leading to leakage of blood or air into body compartments.

Learning Objective Questions

What are the consequences of blood loss?
How is blood circulated around the body?
How does the body maintain blood pressure? Why is it important?
What physiological mechanisms underlie shock?

Tutorial 2 : Trigger 3

INITIAL TREATMENT

The ambulance officers provide oxygen therapy and begin an intravenous (saline)
infusion. They set off on the twenty minute journey to the nearest country hospital.
One of the medical students accompanies the patient in the ambulance. "What is
the best IV fluid to start with? Is he going to bleed more if we give him a lot of
fluid?" asks the student.

Discussion Checklist

What are the priorities in treating this patient? Why?
What intravenous fluids are available? Why not blood or plasma?

Tutor Notes

The principal issue in this trigger is initial management of hypovolaemic shock. Why is
oxygen given? What are the choices of fluids, what are the targets for resuscitation in
terms of pulse, blood pressure and indices of perfusion? What determines which body
compartment/s IV fluids will be distributed to?

The body’s internal environment contains three major fluid compartments – blood plasma,
extracellular fluid (interstitial fluid and lymph) and intracellular fluid. The chemical
composition of these fluids changes constantly in response to the movement of solutes
and water both between the internal and external environment and between each other.
The plasma compartment is separated from the interstitial compartment by the capillary
wall which, in most areas of the body, allows for rapid exchange of water and solutes
between them. The interstitial and intracellular compartments are separated by cell
membranes, most of which allow for the rapid passage of water through protein pores.
Normally the three compartments are in osmotic equilibrium because water is able to shift
rapidly from one to the other.

There are some substantial theoretical issues in the choice of cystalloid or colloid
replacement as initial IV fluid replacement in shock. Consideration of the exchange of fluid
at the capillary membranes in the tissues (the "Starling Forces" concept, where hydraulic
pressure pushes fluid out and osmotic pressure of plasma proteins pulls fluid into the
vascular space) suggests that most of the infused salt solution will end up in the interstitial
fluid and that the expansion of intravascular volume will be only temporary. In practice, a
temporary improvement may be all that is needed, since blood replacement and definitive
surgical haemostasis will be coming within the hour.

Colloid replacement has obvious theoretical advantages. Formulations such as Gelatin
(“Haemaccel”) are economical and free from adverse effects. However, in severe
hypovolaemic shock, or various forms of distributive shock with low peripheral resistance,
there is frequently, impairment of the selectivity of the capillary membrane, so that leakage
of macromolecules into the interstitial space occurs early, facilitating further loss of
intravascular volume as resuscitation proceeds and tissue perfusion improves. Studies
comparing crystalloid and colloid replacement have a long and inconclusive history. It is
probably fair to say that any fluid is a lot better than none, and that results with simple
solutions are comparable to those with early blood replacement. Thus there are
unanswered questions even about the apparently simple choice of solution for initial fluid
replacement.

The question whether hypotension is protective against haemorrhage from internal trauma
sites such as a ruptured spleen is vexed. It is self-evident, when the problem is blood loss,
that stopping the bleeding has the highest priority. However, in the practicalities of
evacuating victims from an accident scene, there is a substantial delay between the time
at which an IV infusion can be started and the later time in an operating theatre when
haemostasis can be achieved for internal injuries. The problem is how much hypotension
might be beneficial? Since falling blood pressure represents the later stages of
hypovolaemic shock, as the compensatory mechanisms fail, it is obviously a knife edge
situation. A recent Cochrane Review (Cochrane Database Syst Rev 2001, 1, CD002245)
found that current evidence on the best fluid administration strategy in bleeding trauma
patients is presently inconclusive. Most practitioners at this point concentrate on achieving
adequate replacement and the earliest possible surgery for definitive haemostasis in
patients with major trauma and blood loss.

Learning Objective Questions

What are the body fluid compartments and what is their relationship to each other?
What concepts underlie fluid replacement therapy?
What are types of IV fluids are available? What are their advantages and disadvantages?
Tutor Guide : Yr 1 Wk 2 "Blood on the Road (cont'd)"

Case Summary

This week, we follow Mark Brown’s progress once he reaches hospital and look more
closely at the major themes of homeostasis and the management of shock. The learning
agenda covers the basic functions of the cardiovascular system in transporting gases,
nutrients and wastes to and from the tissues, and about the regulation of the heart and
cardiac output. In addition, the public health aspects of alcohol and its relationship to road
trauma are also addressed.

When the cardiovascular system loses volume, through blood or fluid loss, there is a
tendency to decrease the cardiac output, drop the arterial blood pressure, and thus reduce
the perfusion of the tissues. Physiological compensation mechanisms intervene, before
there is any detectable decrease in blood pressure to defend against these changes.

For modest losses, such as donating half a litre at the blood bank, there are hardly any
noticeable signs of changes in haemodynamics, or of the compensatory mechanisms
which have corrected and concealed the disturbance. As blood loss becomes more
extensive, the signs of the corrective mechanisms will be more obvious, with accelerated
heart rate and peripheral pallor. Perfusion of life-critical organs is maintained by driving the
heart harder and shutting down lower priority vascular beds such as skin, skeletal muscle
and gut. Both these kinds of compensatory action occur through the efferent pathways of
the sympathetic nervous system. Overflow in sympathetic pathways causes sweat
secretion, leading to the cold, clammy periphery. Note that at this stage of "compensated
shock" we have arterial blood pressure maintained close to normal. Only later, as more
extensive blood loss goes outside the range of the controlling mechanisms, does the
arterial blood pressure fall, with imminent failure of perfusion of the heart and brain.

But why is there a tendency to decrease cardiac output in the first place? Normally, most
of the blood volume is in the larger veins, under a very low pressure. Why does the heart's
stroke volume (the volume pumped from each ventricle with each systolic contraction), fall
as the veins empty?

It turns out that the heart cannot actually provide any suction to assist its filling. It requires
some venous pressure to fill the ventricles for each systolic contraction. As the venous
pressure increases and becomes positive, there is a progressive increase in diastolic filling
of the ventricles, which is promptly translated into increased stroke volume. Conversely,
when the filling pressure is reduced, the stroke volume diminishes. This simple relationship
is the most important and basic concept in cardiovascular regulation - it is usually known
as the "Frank-Starling Principle" or "Starling's Law of the Heart" - and is expressed as a
graph relating venous (filling) pressure on the X-axis to stroke volume or cardiac output on
the Y-axis.

This makes it easy to understand the basic sequence with blood loss. Reduced blood
volume causes reduced venous filling pressure, decreasing the ventricular filling and so
reducing the stroke volume. With reduced stroke volume there is diminished cardiac output
(equal to stroke volume times heart rate), leading to a reduction in arterial blood pressure
(equal to cardiac output times the total peripheral resistance). In the absence of any
compensatory mechanisms, reduced blood pressure therefore leads to reduced perfusion
of the tissues.

There are about eight (depending on exactly how we classify them) distinct control
mechanisms which regulate blood pressure and protect the body against the tendency to
diminished pressure and perfusion that is seen in blood loss. Two principal ones are:

1. The fastest of these is the arterial baroreceptor reflex, which increases heart rate in
response to falling blood pressure. It has very high gain, able to correct about 90% or
more of a perturbation of blood pressure, so it will produce large corrective responses
even though the drop in arterial blood pressure may be undetectable with a
sphygmomanometer.

2. The tachycardia is an excellent initial corrective response. Since cardiac output is the
product of stroke volume and heart rate, increased heart rate is obviously beneficial. More
subtly, regulatory behaviour of the heart in response to sympathetic drive, or in fact
anything that increases rate, will shift that graph of the Frank-Starling relationship to the
left so the heart does better with a given filling pressure.

Why then does the compensation eventually fail? The general picture of regulatory
systems is that they can keep their controlled variable at or near the set point for a certain
range of perturbations - when the disturbance becomes too great, the ability to
compensate is exceeded and the system fails.

In hypovolaemic shock of increasing severity, eventually the perfusion of vital organs will
be compromised. At this point the blood pressure is falling and the patient is close to
death.

Sometimes, when a patient is resuscitated adequately but late, the blood pressure and
tissue perfusion return, only to fail several hours later with the patient dying despite the
best management of fluid replacement. Damage during the ischaemic phase has lead to
irreversible and progressive injury to the myocardium such that contractile effort
diminishes. Damage to the peripheral vasculature and breakdown of epithelial defence
barriers in the gut with overwhelming gram negative infection, can compound this lethal
scenario. This is the sequence of "irreversible shock" where progressive damage will kill
the patient even though resuscitation restores cardiovascular parameters temporarily.

Triggers and Tutor Notes

Tutorial 1 : Trigger 1

EMERGENCY DEPARTMENT

History &Assessment

Mark’s brother, Paul, arrives at the hospital shortly after Mark is brought into A&E.
Paul states that Mark is 19 years old. He usually works as a barman but is currently
unemployed. He smokes 30 cigarettes a day. He is a binge drinker, taking as much
as 200 grams of alcohol (20 standard drinks) in a single sitting, once or twice
weekly. Mark’s father also has a history of heavy alcohol consumption.
On assessment in Emergency, Mark is found to have a compound fracture of the left
femur with partial laceration of the left femoral artery. His blood alcohol level is 0.18
g/dl. He has no significant past medical history.

Discussion Checklist

How does this information affect your appreciation of Mark's problems?

Tutor Notes

Prompts:
What contribution does alcohol make to the health and social costs of motor vehicle
crashes?
What is the relationship between blood alcohol level and risk of MVA?
How is alcohol metabolised in the body? How long will it take before Mark’s blood alcohol
falls to zero?
What implications does this level of alcohol have for Mark’s immediate treatment? How?

This trigger confronts the problem of alcohol and its influence on car crash statistics.
Teenagers tend to binge drink rather than have the steady, night-after-night drinking typical
of the middle aged alcoholic. Mark is obviously very drunk and his blood alcohol, three
times the legal limit, would produce unconsciousness in most people. Nevertheless, this
information does raise questions about the precise relationship between blood alcohol
concentration and risk. Surprisingly, persons at the legal limit have only a modest elevation
of risk but the curve rises exponentially as alcohol level increases. Motor vehicle accident
rates increase with rising blood alcohol levels, roughly doubling at the legal limit and rising
dramatically above that.

Since alcohol is a substantial contributor both to the public health budget and to road
trauma, the strategies for interventions which may minimise alcohol consumption and its
consequences make a good learning objective. There is also a tutorial in this week's
resources on accident prevention strategies.

A side issue that the students may happen to discuss is the effect that very high blood
alcohol levels have on cardiac performance and peripheral resistance. Most general
anaesthetics, ethanol included, have depressant effects on the cardiovascular system.

Learning Objective Questions

How much does alcohol abuse cost in the health care budget?
What interventions may be considered with the young problem drinker?
How significant a factor is alcohol in motor vehicle crashes?
What strategies are available to minimise alcohol abuse and its effects?

Tutorial 1 : Trigger 2

EMERGENCY (cont’d)
Investigations

Despite extensive fluid replacement, Mark’s vital signs are not improving. A chest X-
ray taken in the supine position is cloudy and hard to interpret. He is propped up,
with some difficulty, and another film taken in the erect posture.

ALT="HaemoPneumoThorax">

Discussion Checklist
How does this information help you refine your hypotheses?

Tutor Notes

Prompts:
From where may the air and blood in Mark's chest have come?
In which body compartment are these fluids contained and why have they stayed there?

We now know that blood loss is a major problem with internal bleeding as well as the
visible losses.

The chest X-ray needs careful scrutiny. Firstly, the students need to sort out radio-opaque
objects like tissues show up on X-rays compared to radio-transparent objects like air. X-
rays DARKEN the film; tissue ABSORBS X-rays, so LIGHTENING the film. Lungs are
mostly air, transparent to X-rays, and therefore dark.

The first point about an image is symmetry. The human body is nearly symmetrical, so the
opposite side to the injury provides a "normal control" for comparison. Here we see a
conspicuous opacity on the left that is not present on the right. It has a hard, straight
boundary - a fluid level. The fluid has a similar X-ray density to soft tissue, so the heart
shadow is obliterated. What is the nature of the fluid? There are many causes of pleural
effusions (e.g. malignancy, cardiac failure, infection), but in this case it has to be
something which can appear suddenly in the pleural space - blood is the only reasonable
candidate.

Looking above the opacity, we need to compare the lung fields right and left. Note the
absence of lung markings on the left. Therefore the dark region is AIR, and the lung has
collapsed on that side. So we have leakage of two fluids: air and blood. This can trigger
some PBL brainstorming on the site of the leaks - which organs or structures have been
damaged. Blood in large quantities may come from the heart or great vessels, while air
leaks suggest trauma to the trachea, bronchi or lungs. This is clearly a very technical
emergency, and the students do not need to know much about the actual management of
severe chest trauma, but it provides a good trigger for puzzling about the organisation of
the chest and pleural cavity. Why do the blood and air stay in those boundaries? How can
the lung collapse away from the chest wall? This week they will get into the anatomy labs
and start working on the organisation of the body cavities.

Learning Objective Questions

How are the lungs and chest wall related?
From which structures could blood loss and air leaks arise?
Which structure(s) prevent the blood and air moving out into other tissues?
How are drugs, such as alcohol, metabolised by the body?

Tutorial 1 : Trigger 3

SURGERY
Mark requires open chest surgery to repair lacerations to his left main bronchus and
a pulmonary vein.

Despite being given large volumes of intravenous fluid replacement (plasma volume
expander and then blood as soon as it was available from cross matching), he could
not be stabilised before surgery because of accumulating blood and air in the
pleural space, and ongoing blood loss. During surgery, he continued to experience
episodes of profound hypotension as fluid replacement was unable to keep up with
the losses.

As Mark is recovering consciousness after the surgery which also included
stabilisation of his fractures, the anaesthetist says "We are still not keeping ahead
of this guy's losses. His pulse is about 120, systolic BP only 90 and his peripheral
perfusion is poor. Have we missed something?"

Discussion Checklist

What are now the priorities in treating this patient?

Tutor Notes

Prompts:
Why is it essential to replace blood as early as possible?
What is the significance of the damage to mediastinal structures?
What are the possible causes of shock (apart from hypovolaemia)?

The trigger raises the problem of causes of shock by asking whether something has been
missed. Physiologically, shock is classified into hypovolemic, cardiogenic or distributive.
Hypovolemic shock is due to blood loss, or to other causes of volume depletion such as
dehydration from loss of fluid into the oedematous tissues around surgical wounds or into
the damaged microcirculation of a burns injury. Cardiogenic shock (pump failure) is seen
with severe arrhythmias, or extensive damage to the myocardium in acute infarction, or
compression of the heart by pericardial effusion or bleeding. Distributive shock refers to
failure of the peripheral vasculature, as seen in anaphylaxis or septicaemia. Here the
peripheral resistance has fallen so that there is insufficient pressure to maintain perfusion
of those tissues which have limited capacity for vasodilation - particularly the cerebral,
coronary and renal beds. The relatively high capillary pressure occurring with failure of the
precapillary resistance leads to loss of intravascular volume into the tissue extracellular
space, compounding the problem.

The physiological classification above is very illuminating when discussing mechanisms.
Emergency medicine specialists, however, tend to use empirical lists, which are
operationally useful, such as: bleeding, anaphylaxis, non-sinus arrhythmias, ventilatory
insufficiency, compression of the heart, or embolism (air or thrombus) to the heart, lungs or
coronary arteries.
Referring to Mark’s specific problem, has another cause of shock been missed or is his
continued hypotension simply due to failure to replace lost volume quickly enough? Is
there undetected trauma to the heart, or air embolism from his mediastinal injury? Is there
bleeding in another site, such as the abdomen (ruptured spleen or liver), or have the
losses into his fracture sites been under-estimated? It is too early for gram-negative
septicaemia to have supervened from trauma or ischaemia of the gut, but the issue makes
a useful discussion point for the students.

When we consider the signs and symptoms of shock, there is an interesting physiological
question: which features are caused primarily by the volume loss, and which are the result
of a physiological compensating mechanism? This question helps the students focus their
understanding of the processes of shock and its responses. The general picture of a
regulatory control system (servo control, regulator or negative feedback system are
synonyms for our purposes here) is that some sensor detects the change in the "controlled
variable" (blood pressure in this case) and the control system initiates responses which act
to restore the controlled variable to the "set point" (normal value), so minimising the "error
signal" (difference between what is happening and what should be happening). Provided
the initial perturbation is not too large, the control system holds the controlled variable
close to the set point. Once the perturbation exceeds the limits of compensation, the
system collapses with a sudden onset of large changes in the controlled variable. This is
the general behaviour of any control system, of which the body has hundreds, controlling
just about everything measurable.

When we think in this paradigm, we see that an initial change in hypovolaemia is a
tendency to reduce the blood pressure. Because the regulatory control system has high
gain, and corrects most of the error, this initial change will not be appreciable clinically. We
see a patient in early shock, we have only a general idea what their blood pressure was
before they bled, and we measure blood pressure much less accurately than do the
sensors in the carotid sinus and other parts of the cardiovascular and renal systems. What
we do see however, is the large response which this minimal change can trigger - an
increase in heart rate tending to compensate for the diminished cardiac filling and stroke
volume, and peripheral pallor reflecting generalised vasoconstriction to elevate the
peripheral resistance and sustain blood pressure despite falling cardiac output. In these
terms, Mark is in decompensated shock, past the limit of correction by his control systems.

The question for the students then becomes, how do we assess the adequacy of fluid
replacement and the status of cardiac function and peripheral resistance? What might
happen if we overfill the cardiovascular system in the presence of a damaged heart?

Learning Objective Questions

Which signs of shock are due to compensatory mechanisms?
Classify shock into its basic pathophysiological mechanisms.

Tutorial 2 : Trigger 1

POST-OP
Mark's central venous pressure is monitored while his fluid replacement continues.

The anaesthetist, who is also the hospital's intensivist, says "That is about as high
as we dare bring up the CVP. I wish we had a pulmonary wedge pressure to get the
left ventricular filling pressure!"

Discussion Checklist

What is the objective in monitoring Mark’s CVP? Explain.

Tutor Notes

Prompt:
What is the effect of venous pressure on cardiac function?

The issue now is cardiac function: the relationship of cardiac output to filling pressure.

The fundamental concept here is the positive relationship between the venous or cardiac
filling pressure and the stroke volume (or cardiac output, which is equal to stroke volume
times heart rate). This is the famous Frank-Starling Principle, or Starling's Law of the
Heart. Its importance is that it enables the heart to adapt to variations in venous return
(cardiac input), translating them instantly to cardiac output, without needing intervention by
neurally or hormonally mediated control loops. There is an optimal filling pressure for
maximal cardiac output, which is never reached or even approached in healthy subjects in
normal activities, but which can be exceeded with damaged hearts or by excessive volume
replacement. Excessive venous pressure may result in pulmonary oedema with fluid
spilling over into the alveolar air spaces and compromising gas exchange: the patient with
pulmonary oedema is an acute emergency, blue and choking, coughing up frothy fluid and
extremely distressed.

From this concept of cardiac filling determining cardiac output follows the idea, basic to the
pathophysiology of hypovolemic shock, that reduced venous pressure immediately leads
to reduced cardiac output and therefore reduced arterial blood pressure (BP equals
cardiac output times total peripheral resistance). Likewise, we see the primacy of replacing
intravascular volume to restore cardiac filling. Once we understand the relationship of
filling to output in the Frank-Starling principle, we also see how neurally mediated
compensatory mechanisms can help by shifting the F-S curve to the left, increasing the
output at a given filling pressure. The leftward shift of the F-S curve is the tricky increase in
"inotropic state" which is a special property of cardiac muscle, not seen in skeletal muscle
at all.

From basic muscle physiology, the contractile effort of a muscle is given by preload (how
much is is stretched initially: for the heart this is filling pressure) and afterload (load applied
during contraction: for the heart this is the arterial blood pressure against which it must
contract). The third variable in cardiac output is obviously the heart rate. The fourth
variable is inotropic state, which accounts for variation in contractile effort at constant
preload and afterload: it is mediated by the available store of intracellular calcium for
contraction and varies with sympathetic nervous drive, circulating adrenaline and
angiotensin II, and various drugs which can elevate or reduce contractility.

Learning Objective Questions

What is the relationship between cardiac filling pressure and cardiac output?
What are the consequences of excessive filling pressure, or fluid overload?

Tutorial 2 : Trigger 2

PROGRESS

Mark's arterial blood pressure comes up to around 105/85, with pulse rate of 96 per
min.

"Is he out of the woods now?" asks the student.

"After such a long period of hypotension, the worry is that he will deteriorate from
now on into irreversible shock no matter what we do..."

Ultrasound does not show any mechanical damage to the myocardium or heart
valves, but indicates that his left ventricular ejection fraction is down to 31%. When
asked how bad this was the anaesthetist comments: "It could be worse, but much
below that they don't make it."

Discussion Checklist

What is the significance of these signs with respect to Mark’s overall condition?

Tutor Notes

Prompts:
What is the significance of the reduced pulse pressure?
What is the significance of ejection fraction in cardiac function?
What are the mechanisms of tissue damage leading to irreversible shock?

Now the issue is the question of reversible versus irreversible shock.

Notice that the patient has a low stroke volume. Since he is young, we can assume his
arterial compliance is normal, and therefore the pulse pressure indicates a proportionality
to the stroke volume. A pulse pressure of 105 minus 85 equals 20 mmHg and is about half
the normal value in young people (120/80 -> 40), so his stroke volume is markedly
reduced. Initially, this would have been due to reduced cardiac filling, but now he has
elevated central venous pressure after fluid replacement, so the cause must be cardiac
impairment. A normal left ventricle ejects more than half the end-diastolic volume, so
Mark's myocardium has a serious biochemical injury from the period of ischaemia and
anaerobic metabolism.
Irreversible shock can seem quite paradoxical, in that the patient's blood pressure and
tissue perfusion can return to normal levels with transfusion, only to fall again despite
maintenance of oxygenation and vascular filling. This is seen both in experimental models
of hypovolemic shock and in trauma patients when blood volume is restored after an
extensive period of hypotension and reduced tissue perfusion. The patient's blood
pressure and cardiac output may reach normal levels temporarily, only to deteriorate again
despite maintained cardiac filling pressure, oxygenation and an absence of recognisable
problems in the peripheral vasculature. Once this secondary deterioration sets in, it is
inevitably fatal.

In irreversible shock, cardiac performance decreases despite optimal filling pressure.
Other organs, especially the kidney, also suffer damage during ischaemic episodes.
Mechanisms are not totally clear, but damage to the mitochondria with a failure of energy
production features in most analyses of the problem of cardiac damage leading to death in
irreversible shock. Reactive oxygen species like superoxide and hydroxyl radical are also
damaging to tissues during the hyperaemic phase in reperfusion, so the injury continues
after restoration of the circulation - this mechanism is especially prominent in the kidney.
Thinking of cardiac function in terms of the Frank-Starling curve, the deterioration leads to
a decrease in inotropic state, with a shift of the curve to the right.

Learning Objective Questions

What is irreversible shock?
Which components of cells suffer most severe damage in ischaemia due to shock?
How can myocardial function be measured?
What are the mechanisms of tissue damage leading to irreversible shock?

Tutorial 3 : Trigger 1
Eight hours after his crash, Mark is in a serious but stable condition. He is
transferred to a metropolitan hospital.
END