Transcript Homeostaz - mustafaaltinisik.org.uk

Homeostasis.
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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
COMPARTMENTS
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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 System
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“Open System”. The body exchanges
material and energy with its
surroundings.
Water Steady State.
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Amount Ingested = Amount Eliminated
Water Ingestion
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Drinking (1.4 L/day).
Water contained in Food (0.85L/day).
Metabolism ----> CO2 and H2O
(0.35 L/day).
Water Elimination
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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 (Na+, K+, Ca++)
Steady State.
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Amount Ingested = Amount Excreted.
Normal entry: Mainly ingestion in
food.
Clinical entry: Can include parenteral
administration.
Electrolyte losses
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Renal excretion.
Stool losses.
Sweating.
Abnormal routes: e.g.. vomit and
diarrhea.
Metabolized Substances.
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Chemically altered substances must
also be in balance
Balance sheet: conservation between
substrates and end products.
Compartment.
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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.
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Can be spatially dispersed.
Separated by membranes
Epithelial (or endothelial) barriers (cells
joined by tight junctions)
II. EXPRESSING FLUID
COMPOSITION
Gram Molecular Weight
(GMW).
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Mole (mol) (6.02x1023 molecules).
Atomic weight in grams
Molecules: sum atomic weight
individual atoms.
Physiological Molecular Weights
ATOMIC
SUBSTANCE
Gram Molecular
Weight (g/mol)
MOLECULE
Gram Molecular
Weight (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 Composition
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Percentage
Molality
Molarity
Equivalence
Percent Concentrations:
(Solute / Solvent) x 100
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Body solvent is H2O
 1 ml weighs 1 g.
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(weight/volume) percentages (w/v).
(weight/weight) percentages (w/w).
Clinical chemistries: mg % or mg / dl.
Molality.
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Concentration expressed as:
moles per kilogram of solvent.
Rarely used
Molarity (M).
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Concentration expressed as:
moles per liter of solution.
Symbol “M” means moles/liter not
moles.
Physiological concentrations are low.
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millimolar
micromolar
nanomolar
picomolar
(mM) = 10-3
(mM) = 10-6
(nM) = 10-9
(pM) = 10-12
M
M
M
M
Electrochemical Equivalence (Eq).
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Equivalent -- weight of an ionic
substance in grams that replaces or
combines with one gram (mole) of
+
monovalent H ions.
Physiological Concentration:
milliequivalent.
Electrochemical Equivalence
(Eq).
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Monovalent Ions (Na+, K+, Cl-):
 One equivalent is equal to one GMW.
 1 milliequivalent = 1 millimole
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Divalent Ions (Ca++, Mg++, and HPO42-)
 One equivalent is equal to one-half a
GMW.
 1 milliequivalent = 0.5 millimole
Complications in Determining
Plasma Concentrations.
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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
Composition of Body Fluid
Compartments
Fig 2: Body Water Distribution
Input
RBC
PLASMA WATER
4.5%
BONE
3L
3%
CELL WATER
36% 25 L
INTERSTITIAL
FLUID
COMPARTMENT
11.5%
8L
ECF
24% 17 L
DENSE CONNECTIVE
4.5%
TRANSCELLULAR WATER
1.5%
1L
2L
3L
Total Body Water
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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.
Intracellular Water
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Intracellular fluid
 ~36% of body weight
 25 L in a 70 Kg man.
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Extracellular fluid
 ~24% of body weight
 17 L in a 70 Kg man.
Major Extracellular Fluid
Compartments (11L of ECF)
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Plasma (blood minus the red and white
cells)
 ~3 L in a 70 Kg man
 ~4.5% of body weight.
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Interstitial space (between organ cells)
 ~8 L in a 70 Kg man
 ~11.5% of body weight.
Minor Extracellular
Compartments (6 L of ECF)
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Bone and dense connective tissue
Transcellular water (secretions)
 digestive secretions
 intraocular fluid
 cerebrospinal fluid
 sweat
 synovial fluid.
Blood is Composed of Cells and
Plasma.
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Hematocrit (Hct).
 Fraction of blood that is cells.
 Often expressed as percentage.
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Plasma volume
= Blood volume x (1-Hct).
Ingress and Egress
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Plasma water
 Ingested nutrients pass through plasma on
way to cells
 Cellular waste products pass through
plasma before elimination
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Interstitial space.
 Direct access point for almost all cells of
the body
 Exception -- red and white blood cells
Solute Overview:
Intracellular vs. Extracellular
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Ionic composition very different
Total ionic concentration very similar
Total osmotic concentrations virtually
identical
Figure 3: Summary of Ionic
composition
Protein
Organic Phos.
Inorganic Phos.
Bicarbonate
Chloride
Magnesium
Calcium
Potassium
Sodium
400
300
200
100
0
Plasma
H2O
Interstitial
H2O
Cell
H2O
IV. PROTEINS, OSMOTIC
CONCEPTS, DONNAN
MEMBRANE EQUILIBRIUM
Net Osmotic Force Development
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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 (p).
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The force/area tending to cause water
movement.
p= p
S
S
S
S
S
S
S
S
S
S S
S
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Glucose Example
Initial
Gl
Gl
Gl
10 L
Final
Gl
Gl
15 L
Gl
Gl
10 L
Gl
5L
Osmotic Concentration.
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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 Concentration
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Physiological concentrations:
 milliOsmolar units most appropriate.
 1 mOSM = 10-3 osmoles/L
Biological membranes are not
impermeable to all solutes.
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Endothelial Cell Barriers
 All ions can freely cross the capillary wall.
 Only proteins exert important net osmotic
forces.
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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
Equilibrium.
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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 Law
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The product of Diffusible Ions is the
same on the two sides of a membrane.
Initial
50 K+
50 Pr -
50 K+
50 Cl-
100 Osmoles
Step 2
33 K
33 Cl-
66 Osmoles
Ions
Move
134 Osmoles
33 K
33 Cl-
67 K+
17 Cl50 Pr -
33 ml
67 ml
+
Final
100 Osmoles
67 K+
17 Cl50 Pr -
+
Total Volume
100 ml
H2O
moves
Measurement of Body Fluid
Compartments
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Based on concentration in a well-mixed
compartment:
Concentration =
Amount Injected
Volume of Distribution
Measurement of Body Fluid
Compartments
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Requires substance that distributes
itself only in the compartment of
interest.
Vd =
Amount Injected - Amount Excreted
Concentration after Equilibrium
Total Body Water (TBW)
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Deuterated water (D2O)
Tritiated water (THO)
Antipyrine
Extracellular Fluid Volume
(ECFV)
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Labeled inulin
Sucrose
Mannitol
Sulfate
Plasma Volume (PV)
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Radiolabeled albumin
Evans Blue Dye (which binds to
albumin)
Compartments with no
Compartment-Specific Substance
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Determine by subtraction:
 Intracellular Fluid Volume (ICFV).
ICFV = TBW - ECFV
 Interstitial Fluid Volume (ISFV).
ISFV = ECFV - PV
VI. PRINCIPLES OF H2O
MOVEMENT BETWEEN
BODY COMPARTMENTS
Intracellular
vs.
Extracellular
Principles of Body Water
Distribution.
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Body control systems regulate ingestion
and excretion:
 constant total body water
 constant total body osmolarity
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Osmolarity is identical in all body fluid
compartments (steady state conditions)
 Body water will redistribute itself as
necessary to accomplish this.
Intra-ECF Water Redistribution
Plasma vs. Interstitium
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Balance of Starling Forces acting across
the capillary membrane.
 osmotic forces
 hydrostatic forces
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Discussed in more detail later in course
Intracellular Fluid Volume
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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:
Increased ECF Osmolarity
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Water moves out of cells
 ICF Volume decreases (Cells shrink)
 ICF Osmolarity increases
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Total body osmolarity remains higher
than normal. (Of Course, because...)
Primary Disturbance:
Decreased ECF Osmolarity
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Water moves into the cells
 ICF Volume increases (Cells swell)
 ICF Osmolarity decreases
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Total body osmolarity remains lower
than normal.
 (Of Course, because...)
Plasma Osmolarity Measures
ECF Osmolarity
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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
mOSM
270-290
Clinical Laboratory
Measurement.
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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
Measurement.
[glucose ] [BUN]
P = 2  [Na] 

18
2.8
Effective Osmolarity.
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Urea (BUN) crosses cell membranes just
as easily as water.
 [BUN]E = [BUN]i
 No effect on water movement
Effective Osmolarity.
[glucose]
POSM (effective) = 2  [Na ] 
18

BUN
POSM (effective) = POSM (measured) 
2.8
Osmolar Gap.
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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
CALCULATIONS
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Strategy for solving infusion problems
Use for Workshop
VIII. Common Clinical
Conditions Affecting Body Water
and Electrolytes
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Read on your own
Relate to the Principles we have
discussed
SOLUTIONS USED
CLINICALLY FOR VOLUME
REPLACEMENT THERAPY
Types of Solutions
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Isotonic Solutions --> n.c. ICF
Hypertonic Solutions --> Decrease ICF
Hypotonic --> Increase ICF
Dextrose Solutions
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Glucose is rapidly metabolized to CO2 +
H2O.
The volume therefore is distributed
intracellularly as well as extracellularly.
Saline solutions.
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Come in a variety of concentrations:
hypotonic (eg., 0.2%), isotonic (0.9%),
and hypertonic (eg. 5%).
Dextrose in Saline.
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Again available in various
concentrations.
Used for simultaneous volume
replacement and caloric supplement.
Plasma Expanders.
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Dextran which is a long chain
polysaccharide.
Solutions are confined to the vascular
compartment and preferentially expand
this portion of the ECF.