body fluids
Objectives
In this chapter, you will learn to:
Explain the different body fluid compartments and outline the methods and underlying
principles by which these compartments can be measured
Define osmolarity and osmolality, the effects of osmotic pressure, osmosis and the
pressure of a gas in a solution
Discuss how ions move between biological membranes and between the body and the
external environment
Explain the S-shaped oxygen dissociation curve and how it is affected by carbon monoxide
Discuss the Bohr and Haldane effects and how they affect carbon dioxide transport
Describe the coagulation pathway, including the role of thrombin and platelets, the
events involved in haemostasis, and the resolution of a clot
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Minerals (7%)
Fat (15%)
Water (60%)
20% Extracellular fluid
4% Plasma (non-cellular)
1% transcellular
transcellular
(small percentage of weight)
Synovial joint
Aqueous and
vitreous humour
Cerebrospinal
fluid
P=
In Figure 2.3, osmotic pressure exerted
by the solution forces water to move
from left to right, as hydrostatic
pressure forces movement in the opposite
direction
Pericardium
Perineum
nRT
V
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Spoons
of salt
+NaCl
++NaCl
Osmolarity
Pure water
100%
H2O concentration
Osmolality
Solute concentration
100%
Fig. 2.2 The effect of adding solute to water on water and solute
concentration.
Impermeable
membrane
Passive transport
Impermeable membrane
Semipermeable membrane
Fig. 2.3 Osmosis.
Solute particle
H2O particle
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Lungs
Kidney
GI tract
Blood
plasma
ISF
(Interstitial fluid)
Non-ionic diffusion
Although weak acids and bases cross cell membranes
with difficulty in their ionic and dissociated forms,
some have increased solubility in their undissociated
form. Diffusion of such undissociated substances is
called non-ionic diffusion; it occurs in the kidneys
and gastrointestinal tract.
Skin
ICF
(Intracellular fluid)
[Na+]
[K+]
and:
cation A x anion A = cation B x anion B
Active transport
Carrier proteins can transport substances against their
electrical and chemical gradients by using energy
from ATP hydrolysis. A typical example of active
transport is the Na+/K+-ATPase, which moves Na+ out
of and K+ into a cell.
Simple diffusion
This is responsible for 90% of exchange relating
mainly to net efflux of O2 and glucose from plasma
and influx of CO2 into plasma.
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Fluid and ion movement between the body and the external environment
Filtration
Arteriole
Hydrostatic pressure (mmHg)
Capillary
Venule
Net filtration
PCAP>CAP
35
25
CAP
15
Net influx
CAP>PCAP
Starlings hypothesis
Fluid movement = Kf[(PCAP CAP) (PISF ISF)]
Where PCAP = capillary hydrostatic pressure, PISF =
ISF hydrostatic pressure, CAP = capillary oncotic
pressure, ISF = ISF oncotic pressure and kf = filtration
coefficient which takes account of the capillary
surface area and permeability per unit surface area.
The oncotic pressure of the capillary is 25 mmHg
throughout. Hydrostatic pressure of the capillary,
however, decreases progressively from the
arteriolar end (32 mmHg) to the venous end
(12 mmHg).
Oncotic pressure
Oncotic pressure is the osmotic pressure produced
by the proteins that are confined to a compartment/
space by their relatively large size. Its value remains
constant throughout the capillary. The effect of these
proteins is to draw fluid into the compartment/space
in which they are confined. In the plasma, oncotic
pressure is 17 mmHg but, owing to imbalance of
ions as the result of the Donnan effect, there are more
Na+ ions within the capillary and therefore a higher
osmotic pressure of 25 mmHg.
Hydrostatic pressure
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Intake
Output
+
Evaporation from
respiratory tract
400 mL
2000 mL
Sweat diffusion
400 mL
Oxidative
metabolism
400 mL
H2O
Urine 1500 mL
Faeces 100 mL
Total 2400 mL
Total 2400 mL
Plasma volume
Amount of substance injected
Volume of
distribution = Concen
ntration of substance
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Log concentration
X
X
X
Plasma concentration
of injected
X
substance
X
X
Extrapolate
Time
Fig. 2.7 The dilution principle: single injection method, showing change
in plasma concentration of injected substance with time.
the vascular compartment. Examples include radioiodinated human serum albumin or the diazo
compound Evans blue dye (T-1824).
Thiosulphate.
Inulin (can be excluded from bone and cartilage).
Mannitol.
Blood volume
Continuous infusion
X
X
Time when
infusion stopped
Extrapolation
X
Concentration
X
X
X
Plasma
concentration
of infused
substance
X
X
X
X
Time
C = Plasma concentration at time 0
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Transcellular fluid
Transcellular fluid (TCF) is a small compartment
usually considered as part of the ECF representing
~5% of ECF (~1L) and includes a number of small
volumes such as cerebrospinal fluid, intraocular,
pleural, peritoneal and synovial fluids. To include
digestive secretions (which can be excessive and are,
strictly speaking, outside the body) as transcellular
may be debated.
Plasma
Plasma comprises:
BLOOD PHYSIOLOGY
45%
Cellular
components
Plasma
95%
99%
Platelets
H2O
Proteins
Albumins
Globulins
Others including
fibrinogen
Solutes
Electrolytes
(Na+, Cl-, HCO3-)
Gases
Metabolic
substances
RBCs
(erthrocytes)
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Blood physiology
Cells
Henrys law
The weight of a gas absorbed by a
liquid with which it does not combine chemically
is proportional to the partial pressure of the gas
to which the liquid is exposed.
Note: both partial pressure and solubility
determine the amount of gas absorbed.
Haemoglobin
The molecular structure of this conjugate protein
molecule is largely responsible for its O2-carrying
properties (Figs 2.10 and 2.11). Each of the four subunits
consists of a polypeptide chain attached to a haem
group, which can reversibly bind with one O2 molecule.
Hence, up to four molecules of O2 can combine with
each molecule of haemoglobin (Hb); a combination
that exhibits cooperativity among the four binding sites.
Haemoglobin has a greater affinity for binding the second
and third O2 molecules than the first and fourth, and
these differences in affinity give rise to the characteristic
S shape of the O2 dissociation curve (see later).
amount of dissolved O2
Oxygen transport
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subunit
+
+
Fe2
Fe2
Fe2
Haem group
subunit
pH 7.4.
Temperature 37C.
Normal PCO2 (40 mmHg).
Protoporphyrin
+ iron conc
Globin
2
(141 amino acids)
2
(146 amino acids)
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Blood physiology
Hb saturation (%)
100
75
Mixed
venous blood
(40 53 mmHg)
50
20
15
10
25
0
0
20
40
60
80
100
120
PO2 (mmHg)
140
pH > 7.4.
Cooler temperatures: note that O2 is more
soluble in plasma at lower temperatures.
Normal dissociation
curve
lobin
75
Left
50
Left shift
pH>7.4
PCO2
temperature
Right shift
pH<7.4
PCO2
2,3DPG
temperature
Right
Myog
O2 saturation (%)
100
pH < 7.4.
Temperature > 37C.
PCO2: known as the Bohr effect. This is
attributed to its action on [H+] and is discussed
later in the chapter.
2,3 diphosphoglycerate (2,3-DPG), which
binds to the chains of Hb.
25
0
0
40
80
120
PO2 (mmHg)
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Blood physiology
Dissolved in plasma.
As bicarbonate ions (HCO3) in plasma.
As carbamino compounds (chemical
combination with proteins) in whole blood.
Bicarbonate ions
The majority of CO2 is transported as HCO3: 90%
of CO2 in arterial blood and 60% of CO2 in venous
blood is in this form:
CO2 + H20 H2CO3 H+ + HCO3
Carbamino compounds
In the tissues, CO2 reacts readily with the terminal
amine (NH2) group on blood proteins (i.e. Hb)
to form carbamino compounds including
carbaminoHb that contribute up to 30% of CO2
transport in venous blood. This reaction does not
require an enzyme and occurs more readily with
reduced (less acidic) Hb. At the lungs, CO2 is easily
released by carbamino compounds.
The Haldane effect and the Bohr effect
The carriage of CO2 in the blood is increased by
deoxygenation. This is a result of reduced Hb being a
weaker acid than its oxygenated form. Hence reduced
Hb has the following actions:
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H2O
Red blood
cell
CA
Cell
HCO3-
CO2
CO2 + H2O
O2
HbO2
Carbamino
H+
compounds (oxyhaemoglobin)
H2CO3
HCO3ClChloride
shift
O2 + HHb
Haemostasis
Vasoconstriction
Immediately after an injury to a blood vessel, the
smooth muscle in the vascular wall contracts, decreasing
diameter and blood loss. This occurs in response to:
HCO3 Cl
O2
H++HCO3-
O2+HHb
Carbamino compounds
CO2
Lungs
CO2
HbO2
Red blood
cell
CA
H2O
+
CO2
H2CO3
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Blood physiology
Venous blood
70
60
54
50
50
CO2 content
mL/dL
whole blood
Arterial blood
a
46
40
30
45
50
20
10
0 10 20 30
PCO2
60
80
mmHg
100
Fig. 2.16 Carbon dioxide dissociation curve. For any PCO2, total CO2
content increase as PO2 decreases (Haldane effect). For a change in
PCO2 in the physiological range (a, 40mmHg to v, 47mmHg), total CO2
content changes by ~4mL/dL whole blood.
Adhesion
Damage to the vascular endothelium exposes
collagen and other connective tissue to which
platelets adhere.
Activation
During activation, platelets undergo:
Aggregation
The sticky, activated platelets attract one another and
adhere, forming a loose clump. This platelet plug is
effective at blocking small holes and coagulation will
not be necessary. However, injury to a blood vessel
often requires coagulation.
Coagulation
Coagulation comprises a sequence of enzymecatalysed conversions of inactive factors to more
active forms, culminating in the conversion of fluid
blood into a solid gel or clot.
Blood clot formation begins a matter of seconds
after severe trauma to the vascular wall, and in
minutes after injury to other areas of the body.
Open canaliculous
Large reactive surface
area of
platelet overall
Plasma membrane
Contains phospholipids,
which are used to
synthesize prostoglandins
Glycoproteins
Mitochondrion
Granule
Contains clotting
factor and
platelet-derived
growth factor
Lysosome
Dense body
Contains substances active in platelet plug formation
ATP, ADP, serotonins, Ca2+ and enzymes that produce:
Fibrin stabilizing factor
Thromoxane A2
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is slow (minutes).
2. The extrinsic pathway:
is fast (seconds).
Both pathways produce prothrombinase (prothrombin activator), the formation of which
appears to be the rate-limiting step in haemostasis.
After this stage, pathways follow a common set of
reactions, which is known as the final common
pathway (see Fig. 2.18):
Role of platelets
Role of thrombin
Thrombin formed in the first stage on the final
common pathway exerts positive feedback effects on
the coagulation cascade (Fig. 2.19):
Actions of thrombin
Polymerization of fibrinogen.
Activation of factor XIII, which cross-links fibrin
strands.
Positive feedback effects on the coagulation
cascade.
Arterial thrombi:
Clot retraction
Within a few minutes of its formation, the clot begins
to contract due to platelets applying tension to the
fibrin fibres that are attached to damaged blood
vessels, the ends of which are therefore brought closer
together. In addition, fluid is squeezed out of the clot.
Platelets are suited to clot retraction because they:
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Blood physiology
Extrinsic system
Intrinsic system
XII
Activated XII
Tissue factor release
extrinsic to blood
(tissue thromboplastin)
Platelet release
Ca2+
Activated XI
XI
Activated VII
IX
Activated IX
Ca2+
Common
pathway
Activated X
X
Thrombin
VIII
VII
Ca2+
Activated VIII
Prothrombinase
XIII
Platelet phospholipid
Prothrombin
Ca2+
Thrombin
Ca2+
Activated XIII
Fibrinogen
(soluble)
Fibrin
(insoluble)
Fibrin
polymerization
Platelet phospholipid
V
Ca 2+
Prothrombin
Thrombin
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Fibrinolysis
Plasmin is particularly important for removing
inappropriately formed small blood clots; it acts to
digest fibrin fibres and inactivate clotting substances:
fibrinogen, prothrombin, factors V, VIII and XII.
Plasmin is formed from the inactive plasma enzyme
plasminogen by:
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