Basics Of Fluids Flashcards by Nicholas Hewett

What is osmolality?

Osmolality - number of osmoles of solute per kilogram of solvent. The normal osmolality of ECF is 285-290mosmoles/kg, the same as the ICF and unaltered by temperature
• Brandis has 287mosm/kg for plasma (ECF is 285-290)
• Total plasma osmotic pressure is 5545mmHg

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What is normal osmolality of the blood

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How does osmolality compare between the blood and ICF

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How does temperature effect osmolality?

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WHat is the total osmotic pressure of plasma

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What is tonicity?

Tonicity - effective osmolality of a solution - a measure of only the particles which are capable of ascertain an osmotic force across a cell membrane

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What are colligative properties of solutions

Properties dependent on the number of molecules dissolved in a solvent per unit volume

Vapour pressure
Boiling point
Freezing point
Osmotic pressure

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WHat are examples of colligative properties of a solution

Vapour pressure
Boiling point
Freezing point
Osmotic pressure

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What happens to colligative properties with increasing solute concentration

• Vapour pressure depression
• Boiling point elevation
• Freezing point depression
• Osmotic pressure

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Define osmosis

• Osmosis is the diffusion of solvent molecules into a region in which there is a higher concentration of a solute to which the membrane is impermeable

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What is osmotic pressure

• Osmotic pressure is the excess pressure required to maintain osmotic equilibrium (to prevent movement of the solvent) between a solution and the pure solvent separated by a membrane permeable only to the solvent
• the van ‘t Hoff equation describes osmotic pressure:
◦ P = (nRT) / V
◦ Can also be written as
‣ n x c/M x RT
• c = concentration in g/L
• M = molecular weight of molecules
• where
◦ P is the osmotic pressure,
◦ n is the number of particles into which the substance dissociates, i.e. your sodium acetate dissociates into sodium and acetate, and therefore the n = 2
◦ R is the universal gas constant, which is 0.082 L atm mol-1 K-1
◦ T is the absolute temperature (Kº)
◦ V is the volume

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What is the equation for osmotic pressure?

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What is the Von Hoff equation?

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What factors determine osmotic pressure

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What is one mole

• One mole of a substance contains 6 x 10^23 particles (Avogadros number)

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Define osmole

• An osmole is the amount of substance which must be dissolved in order to produce an Avogadro’s number of particles (6.0221 × 10^23).
◦ For substances which do not dissociate, the molarity and the osmolarity will be the same, whereas for substances that are ionised the osmolarity will be the molarity multiplied by the number of dissociated parts, eg. for sodium chloride the osmolarity will be doubled.

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Define osmolarity

• Osmolarity is the number of osmoles of solute per litre of solution.
◦ Osmolarity depends on the volume of the solution, and therefore on the temperature and pressure of the solvent
◦ Number of dissolved particles without regard for what particles they are
◦ Same as osmotic concentration = osmolality x mass density of water

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What does osmolality depend on? And therefore what factors also affect this?

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Osmolality is

Number of osmoses of solute per kilogram of solvent

Depends on mass which is independent of temperature and pressure

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Which of osmolality and osmolarity is independent of temperature and pressure?

Osmolality

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How is osmolality measured

Freezing point depression - colligative property and therefore dependent on solute concentration

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How is molality different to osmolality?

Molality refers to a specific solute

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Define tonicity

• Tonicity is the osmotic pressure between two compartments, and is related to the difference in the concentration of “effective” osmoles (particles capable of exerting an osmotic force) between them
◦ Effective osmoles are those substances which are unable to penetrate the membrane between compartments, and therefore they are effective in their contribution to the osmotic pressure gradient.
◦ Ineffective osmoles are those that area able to equlibrate between compartments, and that are therefore unable to contribute to the osmotic pressure gradient e.g. urea and glucose; however rapid shifts in these still produce a temporary change in tonicity

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What is an effective osmole

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WHat is an ineffective osmole?

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Reflection coefficient refers to? WHat value represents perfectly permeable vs impermeable?

• Reflection coefficient (σ) is a measure of how permeable a membrane is to a given solute, where σ=0 for a perfectly permeable membrane, and σ=1 for a membrane which is perfectly selective.

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How is oncotic pressure calculated

VanHoff equation

P = nRT / V

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Why are glucose and urea poorly effective osmoles

• Reflective coefficients for small molecules and barrier membranes are very small, in the order of 0.1-0.5; i.e. small molecules equilibrate easily on either side of biological membranes
◦ Thus, small molecules like glucose urea and sodium are not “effective” osmoles for the purposes of generating osmotic pressure gradients.

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What is collloid osmotic pressure

Osmotic pressure contributed by large molecules (MW > 30, 000 Daltons)

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What is the normal total protein level

1mmol/kg

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Is the osmolality of proteins in the blood stream large or small?

Small

High molecular weight therefore not that many particles

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What is the plasma oncotic pressure

25-28mmHg

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How much of plasma oncotic pressure does albumin contribute

65-75%

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What are the components of plasma oncotic pressure

Plasma oncotic pressure is 25-28mmHg

Albumin 65-75% the most dominant component as 45g/L, the most negative, half the size of globulins and double the concentration

Globulins are half the concentration, and double the size of albumin

Fibrinogen the least effective

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What proportion of osmotic pressure in plasma is oncotic pressure?

0.5% of total

25-28mmHg of 5535mmHg

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At what oncotic pressure does oedema occur?

<11mmHg which equates to albumin <20g/L

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What safety factors prevent accumulation of oedema

Increased lymph flow
Increased interstitial fluid volume increases pressure and opposes filtration
Decreased interstitial protein decreases interstitial oncotic pressure

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If you use the Vont Hoff equation to calculate oncotic pressure what value do you get? Why is it different to oncotic pressure?

15mmHg

Gibbs Donnan effect equates to additional 10mmHg

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How does plasma sodium compare to interstitial sodium?

0.4mOsm/kg higher due to Gibbs Donnan effect

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What is the excluded volume effect?

In reference of colloid osmotic pressure it is the volume proteins occupy which essentially increases the concentration of all the ions per unit of volume because there is less solvent to dilute them

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What is the glycocalyx

• Non circulating portion of fluid between the endothelial vessel wall and circulating blood volume contributing 25% of total intravascular volume
• The redistribution of fluid from this to intravascular is thought to account for hyperoncotic albumin volume expansion

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Give the Starling fluid equation

Jv = Lp S [ (Pc - Pi) - σ (Πc - Πi) ]; where

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What is the baseline capillary hydrostatic pressure

‣ 32 mmHg at the arteriolar end of the cpaillary
‣ 15 mm Hg at the venular end
‣ Affected by
• Gravity (eg. posture)
• Blood pressure, eg. venous drainage
• Precapillary vasodilatation, eg. in localised inflammation; vasoconstriction being flow and pressure limiting
• Venodilation/venoconstriction - venoconstriction increases capillary pressure

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Factors which affect capillary hydrostatic pressure

Interstitial hydrostatic pressure is usually? What variation in baseline is seen between different sites in the body? Why?

◦ Pi, interstitial hydrostatic pressure is usually:
‣ negative (-5-0 mmHg) in most tissues (except for encapsulated organs, where it is slightly positive, +3 to +6 mmHg)
‣ Affected by anything that modifies lymphatic drainage, eg.:
• Tourniquet
• Immobility, decreased muscle pump activity
• Lymph node removal
• Inflammation, eg burns (where it becomes extremely negative, eg. -20 to -30 mmHg)

What factors increase or decrease interstitial hydrostatic pressure

What factors alter oncotic pressure in plasma and interstitial? WHat is the baseline oncotic pressure?

• Πc - Πi is the capillary-interstitial oncotic pressure gradient
◦ Πc, capillary oncotic pressure = 25mmHg
◦ Affected by the protein content of blood, eg.:
‣ hypoalbuminaemia (eg. liver disease)
‣ Hypoproteinaemia (eg. malnutrition, nephrotic syndrome)
‣ Hyperproteinaemia e.g. exogenous
◦ Πi, interstitial oncotic pressure = 5 mmHg
‣ Affected by the protein content of interstitial fluid, which is usually low but which can increase in local inflammation

WHat is baseline capillary oncotic pressure

What factors alter capillary oncotic pressure

What is baseline interstitial oncotic pressure?

5mmHg

What is LpS in relation to Starling forces?

What is the reflection coefficient for muscle? Intestine? Lung? What is the significance of this?

• σ is the reflection coefficient for protein permeability and is a dimensionless number which is specific for each membrane and protein - it modifies the oncotic pressure to reflect the effect leakage of protein across the membrane will have on forces and correct the magnitude of the measured gradient to account for he in effectiveness of some of the oncotic pressure gradient
◦ σ = 0 means the membrane is maximally permeable
◦ σ = 1 means the membrane is totally impermeable
◦ In the muscles, σ for total body protein is high (0.9)
◦ In the intestine and lung, σ is low (0.5-0.7)

The balance of Starling forces usually leads to the movement of how much fluid net?

20ml/min out, 18ml/min back in

2mL/min net out
2-4L net out per day

How are the hydrostatic capillary forces different in the lung?

◦ Pc, capillary hydrostatic pressure is lower than in systemic circulation
‣ 13 mmHg at the arteriolar end of the cpaillary
‣ 6 mm Hg at the venular end
‣ Affected by
• Gravity (eg. posture) - quite variable pressures between lung segments, and changes markedly with posture as erect the pressure difference due to gravity is ~25mmHg between apex and base
• Left heart function/LAP - determines venous drainage into LA
• Pulmonary artery pressures - little buffering of microcirculation to changes

What factors specifically change the capillary hydrostatic pressure in the lung

Pulmonary interstitial hydrostatic pressure is what at baseline? How does this compare with elsewhere in the circulation?

◦ Pi, interstitial hydrostatic pressure is usually similar/slightly lower than many other areas in systemic circulation
‣ Negative (-5-0 mmHg) effectivelyt equal to alveolar pressure so changes with the respiratory cycle
‣ High interstitial compliance means large volumes of fluid can accumulate without much pressure rise - surfactant has a role in this at reduing surface tension adn hydrostatic pressure
‣ Affected by anything that modifies lymphatic drainage, eg.:
• Positive pressure ventilation
• Extreme negative pressures with ventilation

Is the interstitial compartment of the lung compliant or resistant to the movement of fluid?

What factors alter lung compliance to fluid movement in?

WHat is the interstitial oncotic pressure of the lung? How is this different to the rest of the body? WHy is it different to the rest of the body?

◦ Πi, interstitial oncotic pressure = 17 mmHg
‣ Higher due to lung lymph - the intersitial oncotic pressure is high indicating significant leak of protein across thin capillary walls under normal circumstances. The reflection coefficient is therefore low (0.5). When systemic oncotic pressure falls as does intersitial
◦ Net oncotic gradient is small and favours reabsorption

How does LpS compare i the lung to the rest of the body?

• Lp S is the permeability coefficient/filtration coefficient of the capillary surface, and is affected by shear stress and endothelial dysfunction.
◦ It is a product of the hydrolic permability coefficient (Lp) and surface area of the capillaries (S) and as the pulmonary capillaries are high surface area thin vessels they still have a much reduced surface area compared to total systemic surface area
◦ High Kf indicates high water permeability

Under normal conditions what is the net movement of fluid in the lung?

Under normal conditions there is a small net outward movement of fluid equal to the pulmonary lymph flow rate. The flow is usually 10-20mls/hr
• The intersitial hydrostatic pressure becomes increasingly negative towards the hilum facilitating drainage and flow is promoted by ventilatory rhythmic compression and one way valves.

How is the Starling fluid equation different in the glycocalyx model?

Jv = Lp S [ (Pc - Pi) - σ(Πesl - Πb) ]

where

Jv is the net fluid transport,
Lp is the hydraulic permeability coefficient,
S is the surface area,
Pc and Pi are the capillary hydrostatic pressure and interstitial hydrostatic pressure
σ is the reflection coefficient for protein,
Πesl is the oncotic pressure in the endothelial glycocalyx layer, and
Πb is the oncotic pressure of the subglycocalyx.

• Reabsorption of interstitial fluid via venulesprobably does not occur - instead ultrafiltered fluid returns as lymph
• Some capillaries vigoroulsy ultrafilter across their entire length e.g. glomerulus
• Others absorb along their entire length e.g. intestinal mucosa
• The endothelial glycocalyx rather than the interstitium should be considered in the equation
◦ 500-2000nm thick hydrogel like layer of membrane bound proteoglycans and glycoproteins lining the vascular tree
◦ The oncotic pressure is instead from the sub-glycocalcyceal space between glycocalyx and vascular endothelium free from protein much of the time –> and thus changes in plasma oncotic pressure or hydrostatic pressure instead redistribute fluid from this
◦ Oncotic pressure gradient opposes but does not reverse the movement of fluid

What is a glycocalyx?

What % of body fluid is in the interstitial space?

25%

What % of lymph returns via the thoracic duct

~80%

Why is interstitial protein low

Protein is poorly diffusable out fo the interstitial space
Proteins bind to and become part of the interstitial space therefore are no longer in solution

WHat is the protein concentration of interstitial fluid

20g/L
Proportionally more albumin as smaller so more of it than fibrinogen or globulins

What is the dominant source of body lymph

The liver 50%

How is liver lymph different to the rest of the body?

60g/L protein
Chylomicrons

Interstitial sodium is

0.95 x plasma sodium

Outline the names of lymph vessels as they progress back to the central circulation

• Lymphatic capillaries (blind open-ended vessels) - single later of endothelial cells, collapse, irregular and discontinuous basement membrane with flap valves
◦ Present in all tissues except cartilage, bone marrow and CNS
• Pre-collecting lymphatics (primary valves)
• Collecting lymphatics (secondary bicuspid valves)
• Lymphangions is the term given to length of lymphatic vessels between two valves
• Lymph nodes
• Thoracic duct empties into the central venous circulation
◦ Left thoracic duct: 83% of total flow, empties into the junction of the left IJ and subclavian veins,
◦ Right side of the head, right chest and right arm all empty into the right subclavian vein.

What s the smallest lymphatic vessel? What are some characteristics

Where do you find the smallest lymphatic vessels? Where do you not?

What propels the flow of lymph?

• Contraction of contractile smooth muscle of the lymphatic vessels, which is peristalsis-like
• Contraction of skeletal muscle surrounding the lymphatics (thus, increases with exercise)
• Transmitted pulsation of neighbouring arterial structures
• Presence of one-way valves
• Decreased intrathoracic pressure associated with normal breathing
• Postural changes (i.e. with sleep)

Function of the lymphatic system

• Return of protein and excess fluid to circulation –> keeps interstitial protein low maintaining oncotic pressure gradient
• Transporting fat in small intestine - 90% of fat absorbed form gut extruded into ISF and passes into central lacteal vessels in villi where fat forms globules called chylomicrons (bypass liver)
• Immunological role
◦ Filtration and removal of bacteria by macrophages in lymph glands
◦ Role of lympahtics in lymphocyte circulation through blood and lymph
‣ and can activate and proliferate in response to antigens

A 70kg person has how much water

42L
60% of total body mass

How is total body water different in women?

50% of total body mass instead of 60%

How does total body water compare in obesity to lean?

Increased total body water,but reduced in proportion to body mass

Adipose tissue is only 10-20% water

Intracellular fluid is what % of body mass? What % of total body water

33% of total body mass
23L
55% of total body water

What regulates intracellular water

Osmosis
Therefore dependent on ECF osmolality

What % of intracellular contents is fluid

70%

What is the viscosity of intracellular water? How is it different to extracellular fluid of similar viscosity?

viscocity is very near water but diffusion through this compartment takes 4x longer

Extracellular fluid volume for a 70kg person

19L
45% of total body water
27% of total body mass

What % of total body mass does extracellular fluid make up?

27%

45% of total body water

Extracellular fluid volume is regulated by?

Sodium - 86% of somaolity, 92% of tonicity

Plasma volume is what % of ECF? L for a 70kg male?

25% of ECF
2.8L

Blood volume is what % of total body fluid

12% of total fluid
7% of total mass
As includes intracellular and extracellular;ar

Interstitial fluid comprises what % of body mass?
What % of total body fluid?
Volume

‣ 12% of body mass, 20% of total fluid 8.4L

Dense connective tissue contains what % of body fluid? % of body mass? How does it behave differently

◦ Dense connective tissue and bone
‣ 15% of total body fluid, 9% of total mass however slow to mobilise and dose not participate in infusion physiology. The rest is functional ECF (i.e. 30%) –> this is why 55% vs 30% and 2:1 is used as the ratio for fluid redistribution because the bone and dense connective tissue does not participate quickly

Describe the components and significance of each portion of ECF

• Extracellular Fluid = 27% (18.9 litres); this volume is regulated by the movement of sodium (contirbuting 86% of CF osmolality, 92% of tonicity - urea/glucose not counted) and 45% of total body water
◦ Plasma volume (2.8L) (1/4 of ECF/ 7.5% of total fluid)
‣ Red cells 2.5% of body mass, 4.5% of total fluid (nearly 2L) BUT inside cells
‣ Blood volume is 12% of total fluid or 7% of body mass
◦ Interstitial and lymph fluid
‣ 12% of body mass, 20% of total fluid 8.4L
◦ Dense connective tissue and bone
‣ 15% of total body fluid, 9% of total mass however slow to mobilise and dose not participate in infusion physiology. The rest is functional ECF (i.e. 30%) –> this is why 55% vs 30% and 2:1 is used as the ratio for fluid redistribution because the bone and dense connective tissue does not participate quickly
◦ Adipose tissue

What is trans cellular fluid? What % of body mass? What % of total body fluid?

• Transcellular fluid: ~1.5% of body mass or 2.5% of total body fluid (1050ml); fluid formed by the secretory activity of cells,
◦ communicates with the intracellular fluid, rather than the interstitial fluid.
◦ exists within epithelium-lined spaces.
‣ Synovial fluid
‣ CSF
‣ Aqueous humour
‣ Bile
‣ Bowel contents
‣ Peritoneal fluid
‣ Pleural fluid
‣ Urine in the bladder

What situations is the Von Hoff equation better at predicting osmolality?

Osmolality and osmotic pressure can be predicted from the concentrations of solutes added to a solution
◦ However, the van ‘t Hoff equation loses its predictive value unless the solution is extremely dilute.
◦ This is because solute particles in the solution will interact in a non-colligative way (i.e. the interaction will depend on their molecular shape, charge, size, etc)
◦ For this reason, the calculation of osmolality can never replace the measurement of osmolality. For example, the calculated osmolality of normal saline is 300 (150 mOsm of sodium and 150 mOsm of chloride), and yet its measured osmolality is 286, which resembles the measured plasma osmolality. The reason for this discrepancy is partly the interaction between the ionised sodium and ionised chloride, and partly the failure of some of the sodium chloride molecules to fully ionise. For basically all solutions in clinical use, some discrepancy like this will exist.

Why is the measurement of osmolality required if we can calculate it?

Osmolality and osmotic pressure can be predicted from the concentrations of solutes added to a solution
◦ However, the van ‘t Hoff equation loses its predictive value unless the solution is extremely dilute.
◦ This is because solute particles in the solution will interact in a non-colligative way (i.e. the interaction will depend on their molecular shape, charge, size, etc)
◦ For this reason, the calculation of osmolality can never replace the measurement of osmolality. For example, the calculated osmolality of normal saline is 300 (150 mOsm of sodium and 150 mOsm of chloride), and yet its measured osmolality is 286, which resembles the measured plasma osmolality. The reason for this discrepancy is partly the interaction between the ionised sodium and ionised chloride, and partly the failure of some of the sodium chloride molecules to fully ionise. For basically all solutions in clinical use, some discrepancy like this will exist.

How is osmolality measured?

◦ Fortunately, the addition of solute to a solvent changes its properties predictably: the freezing point and vapour pressure are lowered, and the boiling point and osmotic pressure are increased.
◦ This change occurs for all colligative properties, which means from the measurement of the change of one colligative property, others can be extrapolated
◦ The relationship between the freezing point and the osmolality is complex and non-linear, but still predictable enough that the measurement of the freezing point of the sample can be used to approximate its osmolality. In its simplest form,
◦ Osmolality = ΔT / -1.86
◦ where ΔT is the measured depression of the freezing point, and -1.86 is the cryoscopic constant for water, which is just another way of saying that one mole of solute added to 1kg of water will depress its freezing point by 1.86º K.

Osmolality calculated it?

Calculated osmolarity = ([Na]× 2 ) + [Glucose] + [urea]

Osmolar gap works because although you are comparing osmolarity with osmolality (measured) the osmolality gap in human plasma is 2%

Why do we compare osmolarity with osmolality?

Calculated osmolarity = ([Na]× 2 ) + [Glucose] + [urea]

Osmolar gap works because although you are comparing osmolarity with osmolality (measured) the osmolality gap in human plasma is 2%

Which of osmolality and osmolarity is calculated?

Osmolarity

Which of osmolarity and osmolality is measured

Osmolality

How are body fluid compartemnts measured?

Indicator dilution techniques

◦ Following the equilibration of the indicator into the compartment of interest, the blood level of that indicator can be measured
◦ The volume of distribution of the indicator can then be calculated:
◦ Volume of the compartment = (dose of marker) / (concentration of marker)

Ideal indicator for indicator dilution technqiues is?

◦ safe
◦ not metabolized - if metabolised then needs to follow first order kinetics
◦ Not rapidly excreted - or if excretion more quick easily measurable amounts of excretion
◦ confined to the compartment of interest and uniformly distributed
◦ not prone to changing the distribution of fluid between compartments.
◦ Easily measured

What tracers are used for indiciator dilution rechnqiues?

◦ Ionics - Bromide, Sulfate, chloride
‣ Small, distirbute easily throughout the whole ECF but may enter cells (overestimating ECF)
◦ Crystalloids - mannitol, inulin
‣ Do not diffuse as easily throughout the ECF underestimating its size

What problems are encountered with ionic tracers for indicator dilution

What problems are encountered with crystalloid tracers for meaurement of body fluids?

What is used to measure total body water

Several indicators for measuring body fluid compartments are noted in popular textbooks:
◦ Total body water: radioactive tritium or deuterium, which distributes into total body water over 3-4 hours

What indicator do we used for extracellualr fluid measurement

◦ Extracellular fluid: bromine-82 or mannitol;
‣ Flaws
* however 82Br also distributes into cells - therefore overestimating ECF
* mannitol increases the extracellular fluid volume
‣ Have to wait a full 24 hours for tracer to enter slow compartments

What indicator do we use for the measurement of plasma volume?

‣ albumin tagged with Evans Blue or radioiodine, provided you adjust for a constant slow leak of albumin into the interstitial space - exponential/logarithmic leak therefore if measurements taken over time extrapolation to time zero can be performed

How do we measure blood volume? What problems are there with this approach?

Plasma volume calculation then figure it out based on haematocrit
‣ Use albumin bound to Evans blue or radioiodine to measure plasma volume and then reverse engineer based on measured haemotocrit
* Blood volume = plasma volume x 100/100-Hct
* The problem is that the venous haematocrit is generally higher as the result of the Hamburger effect. Red cells in vein are bloated with the products of carbon dioxide transport, which is osmotically active, and causes them to swell. Usually a 9% difference - whole body haematocirt being 91% of venous.
* Additionally, in capillaries, axial streaming results in the separation of red cells and plasma, which means that the haematocrit of capillary blood is about 0.20.
* Lastly, red cells in the measuring tube are trapped together with some plasma, and that plasma goes unmeasured (usually 4-8%). Hence, haematocrit is overestimated.
* Pregnancy - blood volume increased by 40-45% (18% increase in red cell mass - 250mls without iron supplementation or 30% with iron supplementation reaching 450mls), plasma volume 50% increase by term - haemodilution

	‣ 53 or 51 radio-Chromium labelled red cells
		* Uneven distribution throughout whole blood as haematocrit varies throughout ciruclation.
		* Sample collected at 10 minutes 
	‣ Separate measurement of plasma volume and redcell volume can be used

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