Homeostasis.

1
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

2
BODY FLUID COMPARTMENTS

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

3
The Body as an Open System

• Open System. The body exchanges material and
  energy with its surroundings.

4
Water Steady State.

• Amount Ingested Amount Eliminated

5
Water Ingestion

• Drinking (1.4 L/day).
• Water contained in Food (0.85L/day).
• Metabolism ----gt CO2 and H2O (0.35 L/day).

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Water 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-).

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Electrolyte (Na, K, Ca) Steady State.

• Amount Ingested Amount Excreted.
• Normal entry Mainly ingestion in food.
• Clinical entry Can include parenteral
  administration.

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Electrolyte losses

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

9
Metabolized Substances.

• Chemically altered substances must also be in
  balance
• Balance sheet conservation between substrates
  and end products.

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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.

11
Compartment Properties.

• Can be spatially dispersed.
• Separated by membranes
• Epithelial (or endothelial) barriers (cells
  joined by tight junctions)

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II. EXPRESSING FLUID COMPOSITION
13
Gram Molecular Weight (GMW).

• Mole (mol) (6.02x1023 molecules).
• Atomic weight in grams
• Molecules sum atomic weight individual atoms.

14
Physiological Molecular Weights
15
Expressing Fluid Composition

• Percentage
• Molality
• Molarity
• Equivalence

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Percent Concentrations (Solute / Solvent) x
100

• 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.

17
Molality.

• Concentration expressed as moles per kilogram
  of solvent.
• Rarely used

18
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 (mM) 10-6 M
• nanomolar (nM) 10-9 M
• picomolar (pM) 10-12 M

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Electrochemical 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.

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Electrochemical Equivalence (Eq).

• Monovalent Ions (Na, K, Cl-)
• One equivalent is equal to one GMW.
• 1 milliequivalent 1 millimole
• Divalent Ions (Ca, Mg, and HPO42-)
• One equivalent is equal to one-half a GMW.
• 1 milliequivalent 0.5 millimole

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Complications in Determining Plasma
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.

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III. Distribution and Composition of Body Fluid
Compartments
23
Fig 2 Body Water Distribution
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Total 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.

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Extracellular Water vs. Intracellular 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.

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Major Extracellular Fluid Compartments (11L of
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.

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Minor Extracellular Compartments (6 L of ECF)

• Bone and dense connective tissue
• Transcellular water (secretions)
• digestive secretions
• intraocular fluid
• cerebrospinal fluid
• sweat
• synovial fluid.

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Blood is Composed of Cells and Plasma.

• Hematocrit (Hct).
• Fraction of blood that is cells.
• Often expressed as percentage.
• Plasma volume Blood volume x (1-Hct).

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Ingress 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

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Solute Overview Intracellular vs. Extracellular

• Ionic composition very different
• Total ionic concentration very similar
• Total osmotic concentrations virtually identical

31
Major Ionic Species

• Principle cations
• Extracellular Na
• Intracellular K
• Principle anions
• Extracellular chloride and bicarbonate.
• Intracellular proteins, aas, and phosphates
• inorganic (HPO42-, H2PO4-)
• organic (amino acids and ATP).

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Figure 3 Summary of Ionic composition
33
IV. PROTEINS, OSMOTIC CONCEPTS, DONNAN MEMBRANE
EQUILIBRIUM
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Net Osmotic Force Development

• 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.

35
Osmotic Pressure (p).

• The force/area tending to cause water movement.

36
Glucose Example
37
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.

38
Osmotic Concentration

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

39
Biological membranes are not impermeable to all
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 cant escape the cell interior.

40
Gibbs-Donnan Membrane 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.

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Figure 5 Donnans Law

• The product of Diffusible Ions is the same on
  the two sides of a membrane.

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Measurement of Body Fluid Compartments

• Based on concentration in a well-mixed
  compartment

43
Measurement of Body Fluid Compartments

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

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Total Body Water (TBW)

• Deuterated water (D2O)
• Tritiated water (THO)
• Antipyrine

45
Extracellular Fluid Volume (ECFV)

• Labeled inulin
• Sucrose
• Mannitol
• Sulfate

46
Plasma Volume (PV)

• Radiolabeled albumin
• Evans Blue Dye (which binds to albumin)

47
Compartments with no Compartment-Specific
Substance

• Determine by subtraction
• Intracellular Fluid Volume (ICFV). ICFV TBW -
  ECFV
• Interstitial Fluid Volume (ISFV). ISFV ECFV -
  PV

48
VI. PRINCIPLES OF H2O MOVEMENT BETWEEN BODY
COMPARTMENTS

• Intracellular
• vs.
• Extracellular

49
Principles of Body Water 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.

50
Intra-ECF Water RedistributionPlasma vs.
Interstitium

• Balance of Starling Forces acting across the
  capillary membrane.
• osmotic forces
• hydrostatic forces
• Discussed in more detail later in course

51
Intracellular 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

52
Primary Disturbance 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...)

53
Primary Disturbance Decreased ECF Osmolarity

• Water moves into the cells
• ICF Volume increases (Cells swell)
• ICF Osmolarity decreases
• Total body osmolarity remains lower than normal.
• (Of Course, because...)

54
Plasma Osmolarity Measures 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 Nap 270-290
  mOSM

55
Clinical Laboratory 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

56
Clinical Laboratory Measurement.
57
Effective Osmolarity.

• Urea (BUN) crosses cell membranes just as easily
  as water.
• BUNE BUNi
• No effect on water movement

58
Effective Osmolarity.
59
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.)

60
VII. EXAMPLE CALCULATIONS

• Strategy for solving infusion problems
• Use for Workshop

61
Strategy for solving infusion problems.

• Osmolarity is the same in all compartments.
• Calculate the initial total body solute as
  (Plasma Osmolarity) x (Total Body Water).
• Calculate the initial extracellular solute as
  (Plasma Osmolarity) x (Extracellular Volume)
• Calculate the new total body solute as Previous
  Amt. Amt. Added.
• Calculate the new total body water as Old TBW
  Added Water.
• Calculate the new total body osmolarity as New
  Total Body Solute divided by New TBW.
• Calculate the new extracellular solute as Old
  Extracellular Solute Added Extracellular
  Solute.
• Calculate the new extracellular volume as New
  Extracellular Solute divided by New Total Body
  Osmolarity.
• Calculate new intracellular volume as New TBW -
  New Extracellular Volume.
• If desired, estimate New Nap as New body
  osmolarity divided by 2.

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Problem 1

• Initial conditions ICF 25 L, ECF 17 L, Nap
  140 mEq/L.
• Calculate the effect on ICFV, ECFV, and Plasma
  Na
• Ingestion of 420 mEq NaCl.
• Answers ICF 23.3 L, ECF 18.7 L, Nap
  150 mEq/L.

63
Problem 2

• Initial conditions ICF 25 L, ECF 17 L, Nap
  140 mEq/L.
• Calculate the effect of each on ICFV, ECFV, and
  Plasma Na.
• Imbibing and absorbing 1.5 L of H2O.
• Answers ICF 25.9 L, ECF 17.6 L, Nap
  135 mEq/L.

64
Problem 3

• Initial conditions ICF 25 L, ECF 17 L, Nap
  140 mEq/L.
• Calculate the effect of each on ICFV, ECFV, and
  Plasma Na.
• Infusing 1.5 L of isotonic saline.
• Answers ICF 25.0 L, ECF 18.5 L, Nap
  140 mEq/L.

65
VIII. Common Clinical Conditions Affecting Body
Water and Electrolytes

• Read on your own
• Relate to the Principles we have discussed

66
Extracellular Sodium

• Hypernatremia Decreased ICF
• Hyponatremia Increased ICF (cell swelling).
• Hyperglycemia
• glucose acts as an effective osmole
• Induce hyponatremia and cell shrinkage
• Cell shrinkage, not the hyponatremia, needs
  correcting.

67
Example Conditions causing Hypernatremia

• Increased insensible water loss.
• Excessive Sweat Loss. Normally, sweat is mainly
  water with only a little sodium.
• Central or nephrogenic diabetes insipidus.
  Decreased ADH secretion or responsiveness to ADH.

68
Example Conditions causing Hyponatremia

• Large water ingestion.
• Syndrome of Inappropriate ADH Secretion (SIADH).
  Too much ADH leads to water retention,
  hyponatremia, and excretion of concentrated urine.

69
Increased ECF volume

• Increased central venous pressure (bulging of the
  jugular veins) in conjunction with edema is often
  indicative of increased extracellular fluid
  volume.
• If osmolarity is normal, the intracellular
  volume is probably normal.

70
Decreased ECF Volume.

• Main danger is hypovolemia which ultimately
  decreases tissue perfusion.
• Clinical presentation includes
• Dry mucous membranes
• Lack of urination
• Tenting of skin
• Slow capillary refill.

71
Isotonic decreases in ECFV

• Little direct effect on cell volume.
• Fluid lost has same osmolarity as ECF.
• Volume loss stimulates thirst and ADH secretion.
• Results in water retention and occasionally,
  secondary hyponatremia.
• Examples
• Vomiting.
• Diarrhea.
• Bleeding.
• Burns. Direct loss of interstitial fluid. In
  addition there is protein loss, so plasma
  compartment contracts.

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SOLUTIONS USED CLINICALLY FOR VOLUME REPLACEMENT
THERAPY
73
Types of Solutions

• Isotonic Solutions --gt n.c. ICF
• Hypertonic Solutions --gt Decrease ICF
• Hypotonic --gt Increase ICF

74
Dextrose Solutions

• Glucose is rapidly metabolized to CO2 H2O.
• The volume therefore is distributed
  intracellularly as well as extracellularly.

75
Saline solutions.

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

76
Dextrose in Saline.

• Again available in various concentrations.
• Used for simultaneous volume replacement and
  caloric supplement.

77
Plasma Expanders.

• Dextran which is a long chain polysaccharide.
• Solutions are confined to the vascular
  compartment and preferentially expand this
  portion of the ECF.