The document discusses body fluid compartments and their compositions. It notes that total body water makes up 60% of body weight, with two thirds located intracellularly and one third extracellularly. The extracellular fluid consists of interstitial fluid and blood plasma. Key electrolytes like sodium, potassium, calcium, and chloride are discussed along with their concentrations in plasma, interstitial, and intracellular fluids. Various volume expanders used to increase blood volume are also described, including crystalloids like saline and lactated Ringer's, as well as colloids like albumin, dextrans, gelatin, hydroxyethyl starch, and polyvinylpyrrolidone. Their mechanisms of action, properties, uses,

1. By
Dr. Alka Bansal
Associate Professor,
Department of Pharmacology,
SMS Medical College, Jaipur

2. BODY FLUIDCOMPARTMENTS
• TBW: 60% of body weight (42L)
• ICF:
- 40% of body weight (28L)
- 2/3rd ofTBW
• ECF: 20% of body weight (14L)
- Interstitial fluid (15% of body
weight, 11L)
- Blood plasma (5% of body weight,
3L)
- 75 to 80% ECF is in interstitial fluid

3. Blood is a fluid connective tissue that
circulate continuously around the
body.
Plasma is a clear, straw coloured,
watery fluid in which several different
types of blood cells are suspended (
plasma is blood devoid of blood cells).
Serum is plasma without clotting
factors

4. DISTRIBUTIONOF ELECTROLYTESAND SUBTANCES IN
BODY FLUIDS
SUBSTANCE PLASMA (mOsm/L H2O) INTERSTITIAL (mOsm/L
INTRACELLULAR
H2O)
(mOsm/L H2O)
Na+ 142 139 14
K+ 4.2 4 140
Ca++ 1.3 1.2 1
Cl- 108 108 4
HCO3- 24 28.3 10
Amino acid 2 2 8
Lactate 1.2 1.2 1.5
Glucose 5.6 5.6 0-20 mg/dL

5. Volume Expanders
 Volume expanders are the intravenous
fluid solutions that are used to
increase or retain the volume of fluid
in the circulating blood.
 Generally volume expanders are used
to replace fluids that are lost due to
illness, trauma or surgery.
They do not carry oxygen .

6. Types of volume expanders
There are two main types of volume expanders:
1. Crystalloids: crystalloids are aqueous
solutions of mineral salts or other water-
soluble molecules. E.g. normal saline,
dextrose, Ringer’s solution etc.
2. Colloids: Colloids are larger insoluble molecules,
such as dextran, human albumin, gelatin, blood.
Blood itself is a colloid.

7. Colloids are better than
Crystalloids because:
 The larger molecules of colloids are
retained more easily in the intravascular
space & increase osmotic pressure.
 So, more effective resuscitation of plasma
volume occurs by colloids than produced
by that of crystalloids.
 Duration of action is relatively longer
than crystalloids.

8. Ideal properties of PVEs.
 Iso-oncotic with plasma
 Distributed to intravascular
compartment only
 Pharmacodynamically inert
 Non-pyrogenic, non-allergenic & non-
antigenic
 No interference with blood grouping or
cross-matching
 Stable, easily sterilizable and cheap.

9. Colloidal Plasma expanders -
 Human albumin
 Dextran
 Degraded gelatin polymer
(Polygeline)
 Hydroxyethyl starch
(Hetastarch/HES)
 Polyvinyl pyrrolidone (PVP)

10. Mechanism of action:
 Generally works on the principle of
osmosis.
 Increases Plasma osmotic pressure,
drawing water into plasma from interstitial
fluid.
 Since the lost blood is replaced with a
suitable fluid, the now diluted blood flows
more easily, even in small vessels. As a
result of chemical changes, more oxygen is
released to the tissues.

11. Important points
 - replace fluid to increase volume as RBCs still
sufficient to supply oxygen.
 Molecular weight of colloids determine their duration
of action and ability to expand blood volume.
 Dextran , HMW starch have negative impact on
coagulation, may induce acute renal failure, allergy.
 Colloids classification-
a)natural-albumin
b)synthetic- gelatin, HES, PVP

12. The Natural Colloid—Human Albumin
 - most abundant protein in human plasma (40-50 g/L), with a total body
content of 4 to5 g/kg.
 - hydrophilic, nonglycosylated protein with a molecular weight of 69 kDa.
 distributed one third to two thirds in the intravascular compartment relative
to the extravascular compartment, and
 accounts for 70% to 80% of the plasma colloid oncotic pressure (COP)
 - capacity to bind cations, anions, and toxins, such as bilirubin, gives it an
important physiological role in buffering the acid-base balance of the blood, in
regulating the ionized fraction of cations including calcium and magnesium,
and in scavenging free radicals and transporting proteins and drugs.
 synthesized in the liver with a mean half-life of 14.8 days and is degraded
mostly in muscle, the liver, and the kidney.
 Hypoalbuminemia from a range of pathologies is a poor prognostic factor.

13. 1.HumanAlbumin
 It is obtained from pooled human plasma.
(Edwin Cohn’s development of a method to isolate albumin in a
safe and stable form from human plasma)
 It can be used without regard to patient’s
blood group and doesn’t interfere with
coagulation.
 It is free of risk of transmission of
hepatitis because the preparation is
heat treated.
-Still first line
St. of
Albumin

14. Contd
…
 Crystalloid solution must be infused
concurrently for optimum benefit.
 It has been used in acute
hypoproteinaemia, acute liver failure
and dialysis.
 It is comparatively expensive.
 Available products:
 Albudac, Albupan 50, 100 ml inj.,
 Albumed 5%, 20% infusion (100 ml)

15. Albumin contd..
 available as iso-oncotic (4%-5%) solutions for intravascular volume
expansion and as hyperoncotic solutions (20%-25%) for the
maintenance of fluid balance between compartments and the
restoration of COP.
 albumin’s position as the benchmark biological therapy in terms of
pathogen safety remains unchallenged.
-as an additive stabilizer for other therapeutics such as recombinant
proteins and monoclonal antibodies, and the so-called “new
generation” formulations of these therapies, which exclude albumin
in the context of enhanced safety are addressing perception rather
than real risk.

16. Dextrans
 are groups of branched polysaccharides derived from
sucrose( beet root) by the action of the bacterium
Leuconostoc mesenteroides.
 different dextran preparations are polydisperse mixtures
grouped on the basis of their average molecular weight,
which is different from the average molecular weight of
the particles with colloid oncotic power, which is
important for their hemodynamic action.
 main types are dextran 40, available as a 10% solution,
and dextran 60 and 70, prepared as a 6% solution.
 molecular weight is the chief determinant of the
pharmacodynamics.

17. a) Dextran 70
1. It is most commonly used
preparation.
2. It expands plasma volume for nearly
24 hrs.
3. Excreted slowly by glomerular
filtration as well as oxidized in body
over weeks .
4. and some amount is
deposited in retuculo-
endothelial cells.

18. Dextran 70 has nearly all the properties of an
ideal plasma except:
 It may interfere with blood grouping and
cross matching.
 It can interfere with coagulation and
platelet function and thus prolong
bleeding time .
 Some polysaccharide reacting antibodies, if
present, may cross react with dextran and
trigger anaphylactic reaction like
Urticaria, itching, bronchospasm, fall in BP.

19. b) Dextran 40

It acts more rapidly than dextrose-70.
It reduces blood viscosity .
It is excreted through renal tubules and occasionally may
produce acute renal failure.
The total dose should not exceed 20 ml/kg in 24 hr.
Dextrans can be stored for 10 years and are cheap so are
the most commonly used plasma expanders.
Caution: Dextran doesn’t provide necessary electrolytes and
can cause hyponatremia or other electrolyte disturbances.

20. 3. Degraded gelatin polymer
(polygeline)
 It is synthetic polymer (polypeptide) of
MW-30,000.
 It doesn’t interfere with blood
grouping and cross matching and
is non-antigenic.
 Expands plasma volume for 12 hrs.
 It is more expensive than dextran and can
also be used for priming of heart-lung and
dialysis machines.
 Brands:
Haemaccel; Seraccel 500 ml vaccine.

21. Gelatin
 Gelatins are manufactured from bovine gelatin, a
derivative of collagen, which is cross-linked, urea linked,
or succinylated to yield the final products.
 The molecular weight ranges from 30 kDa to 35 kDa,
and

23. 4. Hydroxyethyl
starch(Hetastarch)
ulati
on
  It is a complex mixture of ethoxylated amylopectin
of various molecular sizes; average MW 4.5 lacs.
  It maintains blood volume longer.
  It doesn’t cause acute renal failure or
coagulation disturbances.
  It improves hemodynamic status for 24 hrs.

24. Hetastarch contd..
 Adverse effects:
Vomiting, mild fever, itching, chills, flu
like symptoms, swelling of salivary
glands, Urticaria, bronchospasm etc.
 Brand:
Expan 6% inj (100 , 500 ml vac)
It has also been used to improve harvesting
of granulocytes because it accelerates
erythrocyte sedimentation.
Adverse effects: Anaphylactic reactions,
mild fever, chilling, periorbital edema,
Urticaria, itching .

25. 5. Polyvinylpyrrolidine(PVP)
 It is a synthetic polymer of average MW
40,000 used as a 3.5% solution.
 PVP was used as blood plasma
expander for trauma victims after
the 1950s.
 It interferes with blood grouping and cross
matching and is histmine releaser.
 It binds to penicillin and Insulin.

26. Contd
…. It is excreted by kidney and small
amounts by liver into
bile.
 A fraction is stored in RE cells for
prolonged periods.
 It is less commonly used plasma
expander.
Sample of
PVP

27. Other uses of PVP:
 PVP is also used in personal care
products such as shampoos and
toothpaste, hair sprays and gels.
 It is used as binder in many
pharmaceutical tablets.
 PVP added to Iodine forms a complex
called Povidone- Iodine that posses
disinfectant properties. And known
under the trade name of Betadine and
Pyodine.

28. A/E of the Synthetic Colloids
Coagulopathy, renal failure, and circulatory and hepatic complications.
 Volume substitution with fluids other than fresh blood may be expected to lead to a
progressive dilution of the cellular and protein hemostatic components. This occurs for
the anticoagulant as well as the procoagulant proteins, and monitoring with the
thromboelastogram (TEG) shows that acute hemodilution with saline induces a
hypercoaguable state of probably because of the dilution of antithrombin III (ATIII), the
most important physiological anticoagulant, which has a high normal range (plasma
levels of 80%-120%).
 Hemodilution, as a result of albumin infusion, leads to in vitro coagulation
abnormalities at 30% volume replacement, but is not considered to have clinically
significant effects.

29. A/E contd--
 Gelatin has induced postoperative hypercoagulation following joint replacement
surgeryand results in decreased TEG-measured clot strength.It also impaired platelet
aggregation in normal volunteers and during cardiac surgery
 Dextran and HES molecules exert an effect on both primary hemostasis and coagulation
through a drop in the factor VIII/ von Willebrand factor (FVIII/VWF) complex, which is
higher than predicted through dilution
 The incidence of acute renal failure associated with dextran and HES has been reported .

30. CRYSTALLOIDS
• Crystal + oid (resembling a crystal)
• Electrolyte solutions with small molecules that can diffuse
freely throughout the extracellular space
• Relatively low tendency to stay intravascular
• Principal component is inorganic salt sodium chloride (NaCl)
• 75-80% of infused crystalloid is distributed in interstitial space
• Volume resuscitation with crystalloid fluids expand
interstitial volume rather than plasma volume
• Eg: Isotonic saline, Lactated Ringer’s solution, etc.,

31. TYPES OFCRYSTALLOIDS
1.Isotonic crystalloids:
When the concentration of the particles (solutes) is similar to that of
plasma, it doesn't move into cells and remains within the extracellular
compartment thus increasing intravascular volume.
Eg: 0.9% NaCl, Ringer’s lactate, D5W
2. Hypotonic solutions:
Compared with intracellular fluid (as well as compared with isotonic
solutions), hypotonic solutions have a lower concentration of solutes
(electrolytes). These solutions will hydrate cells, although their use
may deplete fluid within the circulatory system.
Eg: 0.45% sodium chloride (0.45% NaCl), 0.33% sodium chloride, 0.2%
sodium chloride, and 2.5% dextrose in water
3. Hypertonic solutions:
Solution that have a higher tonicity or solute concentration. The
osmotic pressure gradient draws water out of the intracellular space,
increasing extracellular fluid volume, so they are used as volume
expanders. Eg: 3% NaCl, D5NS

32. FLUI
D
Na
+
Cl- K+ Ca++ pH GLUCOSE BUFFER OSMO
LA
R
ITY
TONICIT
Y
TYPI
CAL
INDICA
TION
NOR
MAL
PLAS
MA
142 108 4.2 1.3 7.4 ~0.85 HCO3-
~24
mEq/L
~290 N/A N/A
NOR
MAL
SALIN
E
154 154 0 0 5.7 0 0 308 Isotonic Resuscitation
RINGE
R’S
LACTAT
E
130 109 4 3 6.4 0 Lactat
e
28
mEq/L
273 Isotonic Resuscitation
D5W 0 0 0 0 0 50 0 252 Hypotoni
c
Hypernatre
mia,
Hypoglyce
mia

33. ISOTONIC SALINE (Normal saline/NS)
• Prototype crystalloid fluid is 0.9% NaCl
• 9 grams of NaCl per liter
• It's called "normal saline solution" because the percentage of sodium
chloride in the solution is approximate to the concentration of sodium
and chloride in the intravascular space.
Osmolarity = 308 mOsm/L

34. WHEN TO BE GIVEN?1) To treat low extracellular fluid as in fluid volume deficit from hemorrhage,
Severe vomiting or diarrhea, Heavy drainage from GI suction
2) Shock
3) Mild hyponatremia
4) Metabolic acidosis (such as diabetic ketoacidosis)
5) It’s the fluid of choice for resuscitation efforts.
6) It's the only fluid used with administration of blood products.
DISADVANTAGE:-
• Metabolic acidosis – due to high chloride concentration (Hyperchloremic
acidosis)
• Intraoperative infusion of isotonic saline at the rate of 30 ml/kg/h causes
a drop in serum pH from 7.41 to 7.28 after 2 hours

35. RINGER’S LACTATE (HARTMANN’S
SOLUTION)
FEATURES:-
• K+ and Ca++ ion concentration are in appropriate concentrations ofplasma
• Na+ concentration is reduced for electrical neutrality
• Lactate addition requires reduction in chloride concentration which is a close
approximation of plasma chloride concentration
• Thus the risk of hyperchloremic acidosis with large volume infusion of RL is eliminated.
• It is contraindicated as diluents for blood transfusions

36. USES:-
• The most physiologically adaptable fluid because its
electrolyte content is most closely related to the
composition of the body's blood serum and plasma.
• Another choice for first-line fluid resuscitation for
certain patients, such as those with burn injuries.
When to be used?
To replace GI tract fluid losses ( Diarrhea or vomiting )
Fluid losses due to burns and trauma
Patients experiencing acute blood loss or hypovolemia

37. DISADVANTAGES:-
• Ca++ in RL can bind with certain drugs and inactivate or reduce
their effectiveness
• Drugs to be not
Iinfused with RL
are: Aminocaproic
acid Amphotericin,
ampicillin,
thiopentone
• RL is metabolized in the liver, which converts the lactate to bicarbonate.
• RL is administered to patients who have metabolic acidosis not patients with
lactic acidosis
• Not given to patients with liver disease as they can't metabolize lactate

38. D5W (5% of dextrose
in water)• 1 gram dextrose = 3.4 kcal 50 grams = 170
kcal/L
• Osmolarity = 252 mOsm/L
• It is considered an isotonic solution, but when the
dextrose is metabolized, the solution actually
becomes hypotonic and causes fluid to shift into
cells.
• <10% of infused volume of D5W
remains intravascularly
• 2/3rd of infused volume ends up inside cells
• Predominant effect is cellular swelling

39. How does it work?
• D5W provides free water that pass through membrane pores to
both intracellular and extracellular spaces. Its smaller size
allows the molecules to pass more freely between
compartments, thus expanding both compartments
simultaneously
• It provides 170 calories per liter, but it doesn't
replace electrolytes.
• The supplied calories doesn't provide enough nutrition
for prolonged use.
• Uses- hypernatremia and hypoglycemia

40. DISAVANTAGES:-
 D5W is not good for patients with renal failure or cardiac problems
since it could cause fluid overload.
 patients at risk for intracranial pressure should not receive D5W
since it could increase cerebral edema
 D5W shouldn't be used in isolation to treat fluid volume deficit
because it dilutes plasma electrolyte concentrations
Never mix dextrose with blood as it causes blood to hemolyze.
 Not used for resuscitation, because the solution won't remain
in the intravascular space.