colloid, Eugene...
Understanding fluids, urea and electrolyte balance;
a quantitative approach. Part Two.
1
In Part 1 we met Salty Sam and learned about
the tonicity of his body water compartments.
We found that the ECF bears the brunt of
iatrogenic fluid overload and that the plasma
part of ECF contains some larger molecules
like albumin, and cellular components. We will
now consider what implications this has for a
rational approach to fluid therapy.
2
A large multicellular organism like Salty Sam
needs a finely-tuned circulation to deliver
oxygen and nutrients to its most distant parts. At
the arteriolar commencement of a capillary,
water is filtered through the pores to the
interstitial space (ISF) of the ECF; pressure at the
arteriolar part of the capillary (capillary
hydrostatic pressure) exceeds interstitial
hydrostatic pressure and drives filtration.
3
In addition to the two hydrostatic pressures
governing fluid flux across the capillary, we have
to consider two osmotic pressures. The colloid
osmotic pressure of plasma is about 25mmHg
and is mostly (75% in health) attributable to
albumin. The interstitial oncotic pressure is
normally very low, about 5mmHg.
4
As blood progresses through the capillary bed,
water is filtered out and the concentration of
albumin and other large molecules rises,
increasing the oncotic pressure. The capillary
hydrostatic pressure is falling towards venous
levels. At some point, the balance of pressures
changes as the oncotic gradient starts to exceed
the hydrostatic gradient, and water is drawn
back in to the circulation.
5
Just one more bit of physiology to know; the
capillary leak of larger molecules is normally
very small, we talk of systemic capillaries having
a “reflection coefficient of 0.95” where 1.0 would
be totally impermeable to larger molecules, and
there is very little albumin in the interstitial fluid
of most organs.
7
The interstices
8
oedema is a bad thing
Fluid overload greatly increases the flux across
the capillary to the interstitium, and this is NOT
a good thing. The space is very compliant; at a
pressure of 3mmHg above atmospheric its
volume could be doubled from 12 to 24 litres,
and doubled again to 48 litres at 6mmHg. The
thin-film distribution system breaks down as
rivulets of fluid form, and then substantial
rivers of ISF aggregate, leaving some cells
starved of nutrients in stagnant pools of
accumulating waste products.
9
Let’s get back to Salty Sam and Dr Eugene. A few
hours after his operation, Sam’s blood pressure
started to fall and his heart rate started to rise. Dr
Eugene diagnosed haemorrhage of more than
15% blood volume as the likeliest cause, and
notified the surgeon.
10
15% of Sam’s blood volume would be about
600ml. If you choose to use a crystalloid (sodium
130-155) which is distributed throughout the
ECF, you should give at least twice 600 (1,200ml)
rapidly to compensate. If you choose a 4%
gelatin, which is about 80% effective as a blood
volume replacement, use at least 750ml. If you
choose a 6% starch solution which is 100%
effective, 600ml will do. Note they must be given
very rapidly in this situation, via a short wide
bore cannula.
11
The evidence base shows no outcome difference
between colloid or crystalloid resuscitation in
acute haemorrhage, and as crystalloids are cheap
and non-allergenic they are widely
recommended! Dr Eugene’s i.v. resuscitation and
Dr Knife’s operation to stop the haemorrhage
saved Salty Sam on this occasion.
12
Middleton-on-Sea Infirmary has a problem with
hospital-acquired infections, and a week later we
return to find Salty Sam being admitted to the
ICU. His systolic arterial pressure is less than 90,
and a rapid 500ml bolus of crystalloid makes no
difference to his arterial or venous pressures. A
blood culture taken yesterday is growing Gram-
negative rods.
13
Capillary leak.
Systemic inflammation reduces capillary
reflection coefficients and the trans-capillary
escape rate of albumin (which is normally very
low) may increase by a thousand fold or more.
At the same time, myocardial and arteriolar
contractility are suppressed (mostly by iNO
synthase activity) so that arterial blood pressure
falls, while pulmonary artery pressure rises.
16
Well done if you remembered the lymphatic
drainage via the thoracic duct to the superior
vena cava.
progress in fluid
balance, extravascular 2500
oxygen tension
difference. 0
4h 8h 12h 16h 20h 24h 28h 32h
18
What are the criteria for Acute Respiratory
Distress Syndrome? Look back at Sam’s chart
on the last slide, at how many hours did he
fulfill the criteria for ARDS?
19
ARDS is a Syndrome, not a disease. Criteria
include acute pulmonary oedema not due to
heart failure or fluid overload (“non-cardiogenic
pulmonary oedema”), hypoxaemia, and reduced
pulmonary compliance. At 20h Sam had both
pulmonary oedema and hypoxaemia.
21
ECF volume, including plasma volume, will be
increased, but the colloid osmotic pressure of the
plasma will be further reduced. There is a
substantial risk of oedema if therapy continues
beyond the amount needed to restore plasma
volume to an adequate level.
22
If Dr Eugene had used colloids as well as
crystalloids, what difference would you expect
in haemodynamics and water flux?
23
Colloidal molecules with substantial molecular
weight (150 or more) would be retained within
the plasma volume, increasing both the
hydrostatic pressure gradient that drives water
into the interstitial space at the arteriolar
capillary, and the oncotic pressure which draws
water back into the venular capillary. The total
volume transfused to resuscitate the plasma and
ECF volume would be smaller. The onset of
pulmonary oedema might have been delayed or
even prevented.
24
3.500
1.750
4% on blood volume.
0
5
7
blood volume
2.775
0.925
blood volume
25
a gelatin molecule (MW 40,000) once cleared
leaves no osmotic effect.
26
Reflect on the relative sizes of the extracellular
fluid volume and the plasma volume. Colloids
are a rational choice for resuscitating the
plasma volume, but if you intend to resuscitate
the ECF as a whole, what is a rational ratio of
crystalloid to colloid to prescribe?
27
As a practical approximation, 500 ml of colloid
for every 2 litres of crystalloid would be
reasonable.
28
As salt and water are lost from the circulation
faster than the colloid, there is a very real risk of
hyperosmotic plasma which has been implicated
in causing renal failure. Small starch molecules
are believed to be cleared by phagocytosis, and
the macrophages may be overwhelmed by
excessive amounts of starch. Skin itching is
associated with starch-laden macrophages in the
dermis.
29
Sam remained oliguric in spite of fluid
resuscitation, his pH was 7.15, potassium
6.7mmol/l and urea 40mmol/l. Dr Eugene started
haemofiltration. The filtrate is plasma water with
ions and small molecules like urea, while the
filtrate-replacement solution is urea-free.
31
With plasma urea 40mmol/l and urea
production at 600mmol/day, what daily
volume of filtration would be needed just to
stop the plasma urea rising?
32
15 litres per day of filtrate at 40mmol/L balances
production of 600mmol/day. More than 15 litres
per day will cause the plasma urea to fall.
34
Further reflections...
the rational use of colloids enables you to
manipulate plasma volume independently of
the ISF volume and protect the plasma’s colloid
oncotic pressure.
36