Homeostasis.Homeostasis.

Definition: Processes by which bodily equilibrium is maintained constant.

Examples of Bodily homeostasis:» temperature»blood pressure»heart rate»blood glucose level, etc.»body fluid composition

BODY FLUID BODY FLUID COMPARTMENTSCOMPARTMENTS

General Goal:

To describe the major body fluid compartments, and the general processes involved in movement of water between extracellular and intracellular compartments.

The Body as an Open The Body as an Open SystemSystem “Open System”. The body

exchanges material and energy with its surroundings.

Water Steady State.Water Steady State.

Amount Ingested = Amount Eliminated

Water IngestionWater Ingestion

Drinking (1.4 L/day). Water contained in Food

(0.85L/day). Metabolism ----> CO2 and H2O

(0.35 L/day).

Water EliminationWater Elimination

Urinary loss (1.5 L/day). Fecal loss (0.2 L/day). Insensible H2O loss (0.9 L/day) Sweat Losses. Pathological losses.

vascular bleeding (H20, Na+)

vomiting (H20, H+)

diarrhea (H20, HCO3-).

Electrolyte (NaElectrolyte (Na++, K, K++, Ca, Ca++

++) Steady State.) Steady State. Amount Ingested = Amount

Excreted. Normal entry: Mainly ingestion in

food. Clinical entry: Can include

parenteral administration.

Electrolyte lossesElectrolyte losses

Renal excretion. Stool losses. Sweating. Abnormal routes: e.g.. vomit and

diarrhea.

Metabolized Substances.Metabolized Substances.

Chemically altered substances must also be in balance

Balance sheet: conservation between substrates and end products.

Compartment.Compartment.

DEFINITION. A non-specific term to refer to a region in the body with a unique chemical composition or a unique behavior.

Distribution of substances within the body is NOT HOMOGENEOUS.

Compartment Properties.Compartment Properties.

Can be spatially dispersed. Separated by membranes Epithelial (or endothelial) barriers

(cells joined by tight junctions)

II. EXPRESSING FLUID II. EXPRESSING FLUID COMPOSITIONCOMPOSITION

Gram Molecular Weight Gram Molecular Weight (GMW).(GMW).

Mole (mol) (6.02x1023 molecules). Atomic weight in grams Molecules: sum atomic weight

individual atoms.

Physiological Molecular Physiological Molecular WeightsWeights

ATOMICSUBSTANCE

Gram Molecular Weight (g/mol)

MOLECULE Gram MolecularWeight (g/mol)

Sodium (Na) 22.99 Bicarbonate ( HCO3- ) 61.02

Potassium (K) 39.10 Phosphate, monobasic ( H2PO4- ) 96.99

Calcium (Ca ) 40.08 Phosphate, dibasic (HPO42- ) 95.98

Magnesium (Mg) 24.31 Phosphate (PO43- ) 94.97

Chlorine (Cl) 35.45 Ammonia ( NH3) 17.03

Phosphorous (P) 30.97 Ammonium ( NH4+ ) 18.04

Carbon (C) 12.01 Glucose ( C6 H12O6 ) 180.16

Hydrogen (H) 1.008 Urea ( H2NCONH2) 60.06

Oxygen (O) 16.00 B.U.N. ( N2 ) 28.02

Nitrogen (N) 14.01

Expressing Fluid Expressing Fluid CompositionComposition

Percentage Molality Molarity Equivalence

Percent Concentrations:Percent Concentrations: (Solute / Solvent) x (Solute / Solvent) x

100100 Body solvent is H2O

1 ml weighs 1 g. (weight/volume) percentages (w/v). (weight/weight) percentages (w/w). Clinical chemistries: mg % or mg / dl.

Molality.Molality.

Concentration expressed as: moles per kilogram of

solvent. Rarely used

Molarity (M).Molarity (M).

Concentration expressed as: moles per liter of solution.

Symbol “M” means moles/liter not moles.

Physiological concentrations are low.» millimolar (mM) = 10-3 M» micromolar (M) = 10-6 M» nanomolar (nM) = 10-9 M» picomolar (pM) = 10-12 M

Electrochemical Electrochemical Equivalence (Eq).Equivalence (Eq).

Equivalent -- weight of an ionic substance in grams that replaces or combines with one gram (mole) of monovalent H+ ions.

Physiological Concentration:milliequivalent.

Electrochemical Electrochemical Equivalence (Eq). Equivalence (Eq).

Monovalent Ions (Na+, K+, Cl-): One equivalent is equal to one GMW. 1 milliequivalent = 1 millimole

Divalent Ions (Ca++, Mg++, and HPO4

2-) One equivalent is equal to one-half a

GMW. 1 milliequivalent = 0.5 millimole

Complications in Complications in Determining Plasma Determining Plasma

Concentrations.Concentrations. Incomplete dissociation (e.g. NaCl). Protein binding (e.g. Ca++) Plasma volume is only 93% water.

The other 7% is protein and lipid. »Hyperlipidemia»Hyperproteinemia.

III. Distribution and III. Distribution and Composition of Body Fluid Composition of Body Fluid

CompartmentsCompartments

Fig 2: Body Water Fig 2: Body Water DistributionDistribution

CELL WATERCELL WATER36% 25 L

ECFECF24% 17 L

RBC

DENSE CONNECTIVE

4.5% 3 L

BONE

3% 2 L

INTERSTITIALFLUID

COMPARTMENT

11.5% 8 L

PLASMA WATER

4.5% 3 L

TRANSCELLULAR WATER

1.5% 1 L

Input

Total Body WaterTotal Body Water

Individual variability

= f(lean body mass) 55 - 60% of body weight in adult

males 50 - 55% of body weight in adult

female ~42 L For a 70 Kg man.

Extracellular Water vs. Extracellular Water vs. Intracellular WaterIntracellular Water

Intracellular fluid ~36% of body weight 25 L in a 70 Kg man.

Extracellular fluid ~24% of body weight 17 L in a 70 Kg man.

Major Extracellular Fluid Major Extracellular Fluid Compartments (11L of Compartments (11L of

ECF)ECF) Plasma (blood minus the red and white cells) ~3 L in a 70 Kg man ~4.5% of body weight.

Interstitial space (between organ cells) ~8 L in a 70 Kg man ~11.5% of body weight.

Minor Extracellular Minor Extracellular Compartments (6 L of Compartments (6 L of

ECF)ECF) Bone and dense connective tissue Transcellular water (secretions)

digestive secretions intraocular fluid cerebrospinal fluid sweat synovial fluid.

Blood is Composed of Cells Blood is Composed of Cells and Plasma.and Plasma.

Hematocrit (Hct). Fraction of blood that is cells. Often expressed as percentage.

Plasma volume = Blood volume x (1-

Hct).

Ingress and EgressIngress and Egress

Plasma water Ingested nutrients pass through plasma

on way to cells Cellular waste products pass through

plasma before elimination Interstitial space.

Direct access point for almost all cells of the body

Exception -- red and white blood cells

Solute Overview:Solute Overview: Intracellular vs. Intracellular vs. ExtracellularExtracellular Ionic composition very different Total ionic concentration very

similar Total osmotic concentrations

virtually identical

0

100

200

300

400

Protein

Organic Phos.

Inorganic Phos.

Bicarbonate

Chloride

Magnesium

Calcium

Potassium

Sodium

Figure 3: Summary of Figure 3: Summary of Ionic compositionIonic composition

InterstitialH2O

PlasmaH2O

CellH2O

IV. PROTEINS, OSMOTIC IV. PROTEINS, OSMOTIC CONCEPTS, DONNAN CONCEPTS, DONNAN MEMBRANE EQUILIBRIUM MEMBRANE EQUILIBRIUM

Net Osmotic Force Net Osmotic Force DevelopmentDevelopment

Semipermeable membrane. Movement some solute obstructed. H2O (solvent) crosses freely. End point:

Water moves until solute concentration on both sides of the membrane is equal.

OR, an opposing force prevents further movement.

Osmotic Pressure (Osmotic Pressure (). ).

The force/area tending to cause water movement.

SS

S

S S S

S S SS

S

S S

p

Glucose ExampleGlucose Example

Gl Gl Gl Gl

Gl Gl Gl Gl

Initial

Final

10 L 10 L

15 L 5 L

Osmotic Concentration.Osmotic Concentration.

Proportional to the number of osmotic particles formed.

Assuming complete dissociation: 1.0 mole of NaCl forms a 2.0 osmolar

solution in 1L. 1.0 mole of CaCl2 forms a 3.0 osmolar

solution in 1L.

Osmotic ConcentrationOsmotic Concentration

Physiological concentrations: milliOsmolar units most appropriate. 1 mOSM = 10-3 osmoles/L

Biological membranes are Biological membranes are not impermeable to all not impermeable to all

solutes. solutes. Endothelial Cell Barriers All ions can freely cross the capillary wall. Only proteins exert important net

osmotic forces. Cell Membrane Barriers

Membrane pumps effectively keep Na+ from entering cells, thus forming a virtual barrier.

Proteins can’t escape the cell interior.

Gibbs-Donnan Membrane Gibbs-Donnan Membrane Equilibrium.Equilibrium.

Proteins are not only large, osmotically active, particles, but they are also negatively charged anions.

Proteins influence the distribution of other ions so that electrochemical equilibrium is maintained.

Figure 5: Donnan’s LawFigure 5: Donnan’s Law The product of Diffusible Ions

is the same on the two sides of a membrane.

33 K+

33 Cl-

67 K+

50 Pr -

17 Cl-Step 2

66 Osmoles 134 Osmoles

50 K+ 50 K+

50 Cl- 50 Pr -Initial

100 Osmoles 100 Osmoles

Final

33 ml 67 ml

33 K+

33 Cl-

67 K+

50 Pr -

17 Cl-

Total Volume100 ml

IonsMove

H2Omoves

Measurement of Body Measurement of Body Fluid CompartmentsFluid Compartments

Based on concentration in a well-mixed compartment:

Concentration =Amount Injected

Volume of Distribution

Measurement of Body Measurement of Body Fluid CompartmentsFluid Compartments

Requires substance that distributes itself only in the compartment of interest.

Vd =Amount Injected - Amount Excreted

Concentration after Equilibrium

Total Body Water (TBW)Total Body Water (TBW)

Deuterated water (D2O) Tritiated water (THO) Antipyrine

Extracellular Fluid Volume Extracellular Fluid Volume (ECFV)(ECFV)

Labeled inulin Sucrose Mannitol Sulfate

Plasma Volume (PV)Plasma Volume (PV)

Radiolabeled albumin Evans Blue Dye (which binds to

albumin)

Compartments with no Compartments with no Compartment-Specific Compartment-Specific

SubstanceSubstance Determine by subtraction:

Intracellular Fluid Volume (ICFV).ICFV = TBW - ECFV

Interstitial Fluid Volume (ISFV).ISFV = ECFV - PV

VI. PRINCIPLES OF HVI. PRINCIPLES OF H22O O MOVEMENT BETWEEN MOVEMENT BETWEEN BODY COMPARTMENTSBODY COMPARTMENTS

Intracellularvs.

Extracellular

Principles of Body Water Principles of Body Water Distribution.Distribution.

Body control systems regulate ingestion and excretion: constant total body water constant total body osmolarity

Osmolarity is identical in all body fluid compartments (steady state conditions) Body water will redistribute itself as

necessary to accomplish this.

Intra-ECF Water Intra-ECF Water RedistributionRedistribution

Plasma vs. InterstitiumPlasma vs. Interstitium Balance of Starling Forces acting across the capillary membrane. osmotic forces hydrostatic forces

Discussed in more detail later in course

Intracellular Fluid VolumeIntracellular Fluid Volume ICFV altered by: changes in

extracellular fluid osmolarity. ICFV NOT altered by: iso-osmotic

changes in extracellular fluid volume.

ECF undergoes proportional changes in: Interstitial water volume Plasma water volume

Primary Disturbance:Primary Disturbance: Increased ECF Osmolarity Increased ECF Osmolarity

Water moves out of cells ICF Volume decreases (Cells shrink) ICF Osmolarity increases

Total body osmolarity remains higher than normal. (Of Course, because...)

Primary Disturbance:Primary Disturbance: Decreased ECF Decreased ECF

OsmolarityOsmolarity Water moves into the cells ICF Volume increases (Cells swell) ICF Osmolarity decreases

Total body osmolarity remains lower than normal. (Of Course, because...)

Plasma Osmolarity Plasma Osmolarity Measures ECF OsmolarityMeasures ECF Osmolarity

Plasma is clinically accessible. Dominated by [Na+] and the

associated anions Under normal conditions, ECF

osmolarity can be roughly estimated as:

POSM = 2 [Na+]p 270-290 mOSM

Clinical Laboratory Clinical Laboratory Measurement.Measurement.

Includes contributions from glucose and urea.

Contribution from glucose and urea normally small. Glucose normally 60-100 mg/dl BUN normally 10-20 mg/dl

Clinical Laboratory Clinical Laboratory Measurement.Measurement.

P 2 [Na]glucose

18

[BUN]

2.8

[ ]

Effective Osmolarity.Effective Osmolarity.

Urea (BUN) crosses cell membranes just as easily as water. [BUN]E = [BUN]i

No effect on water movement

Effective Osmolarity.Effective Osmolarity.

P (effective) 2 [Na ][glucose]

18

P (effective) = P (measured)BUN

2.8

OSM

OSM OSM

Osmolar Gap.Osmolar Gap.

Posm (measured) - Posm (calculated) Suggests the presence of an

unmeasured substance in blood. e.g. following ingestion of a foreign

substance (methanol, ethylene glycol, etc.)

VII. EXAMPLE VII. EXAMPLE CALCULATIONSCALCULATIONS

Strategy for solving infusion problems

Use for Workshop

VIII. Common Clinical VIII. Common Clinical Conditions Affecting Body Conditions Affecting Body

Water and ElectrolytesWater and Electrolytes

Read on your own Relate to the Principles we have

discussed

SOLUTIONS USED SOLUTIONS USED CLINICALLY FOR VOLUME CLINICALLY FOR VOLUME REPLACEMENT THERAPYREPLACEMENT THERAPY

Types of SolutionsTypes of Solutions

Isotonic Solutions --> n.c. ICF Hypertonic Solutions --> Decrease

ICF Hypotonic --> Increase ICF

Dextrose SolutionsDextrose Solutions

Glucose is rapidly metabolized to CO2 + H2O.

The volume therefore is distributed intracellularly as well as extracellularly.

Saline solutions.Saline solutions.

Come in a variety of concentrations: hypotonic (eg., 0.2%), isotonic (0.9%), and hypertonic (eg. 5%).

Dextrose in Saline.Dextrose in Saline.

Again available in various concentrations.

Used for simultaneous volume replacement and caloric supplement.

Plasma Expanders.Plasma Expanders.

Dextran which is a long chain polysaccharide.

Solutions are confined to the vascular compartment and preferentially expand this portion of the ECF.