1. Body Fluids and Their Compartments
Dept. Pharmacology, ext. 3477
NOTE THAT SEVERAL OF THE SLIDES IN MY SERIES OF RENAL LECTURES CONTAIN FLASH ANIMATIONS THAT MUST BE PLAYED TO HAVE MEANING...
THESE ANIMATIONS ARE ACCESSIBLE TO YOU, BUT REQUIRE AN INTERNET CONNECTION.

2. Student Objectives
Understand how body fluid compartments differ with respect to volumes and ionic composition
Understand the driving forces responsible for fluid shifts across cell membranes and the capillary wall
Understand the following terms: molarity, equivalence, osmotic pressure, osmolarity, osmolality, oncotic pressure and tonicity
Understand the causes and consequences of pathophysiological expansion and contraction of the extracellular and intracellular volumes
Understand the ICF and ECF volume changes associated with the infusion of isotonic, hypotonic or hypertonic saline, 5% albumin and 5% dextrose

3. The kidneys maintain volume and composition of the body fluids constant DESPITE wide variation in the daily intake of water and solutes.

4. To accomplish this, water and solutes must be excreted separately (to the extent possible) by the kidneys.

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6. We will initially focus on forces governing distribution of fluid between body compartments …
Why is this important?
DWW Flash animation: another illustration of the question
DWW Flash animation: consequences of change in extracellular osmolarity on RBC’s in a beaker
DWW Flash animation: consequences of low extracellular osmolarity… consider the brain
All animations made by me should be accessible on your student web site

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10. So, why is it important that our body maintains both extracellular volume and composition constant? What processes do the kidneys use to do this?

11. Summary of Body Fluid Regulation Pathways for a 70 kg person
Note that intake/output exchange of water and solute occurs with plasma
The capillary membrane is the first fluid barrier, found between the extracellular subcompartments, with a one-way lymphatic shunt returning interstitial fluid to the plasma
The cell membrane is the second barrier to fluids, separating intracellular from extracellular fluids

12. Terminology - molarity
molarity: grams of substance divided by molecular weight per 1 liter
typically used for uncharged molecules such as glucose and urea
Example: glucose has a molecular (formula) weight of 180 g/mole
180 g/L = 1 Molar glucose (1 M glucose)
180 mg glucose/L = 1 mM glucose

13. Terminology - equivalents
equivalents: used to express concentrations of ions per liter, it equals the absolute value of valence times molarity
Example: F.W. of CaCl2 · 6H2O = g/mole
219.4 mg of CaCl2 · 6H2O/L gives a 1 mM solution
CaCl2 dissociation gives
1 mmol of Ca2+ or 2 mEq/L of Ca2+… ( = valence of 2 * 1 mM)
2 mmol of Cl- or 2 mEq of Cl- … ( = valence of 1 * 2 mM)

14. Ion Distribution Between ICF & ECF 1
The “alternator” that keeps the “battery” charged
Na+
Na+-K+-ATPase K+
+ −
Why is this a relative (+)?

15. Ion Distribution Between ICF & ECF 2
The kidneys maintain the extracellular SMALL ion concentrations from which the cells of the body extract their needs
Major sources: liver, lymphocytes
Cell membrane permeabilities, pumps, need for electroneutrality maintain gradients; proteins only cross by endo- or exocytosis
Note the high intracellular protein concentration

16. Typical 70 kg Male Body Water
≈ 60% of body weight, 42 L

17. Body Water VOLUME Calculations
Markers when equilibrated:
3H2O for Total Body Water Vol.
Inulin for Extracellular Fluid Vol.
Evan’s Blue Dye for Plasma Vol.
(it binds tightly to albumin so confined to vasculature)
Inject known volume (V1) of known concentration (C1) IV with known distribution, allow equilibration, and measure its concentration (C2).
C1  V1 = C2  V2, so V2 = C1  V1 / C2
ICF = TBW – ECF; IS = ECF – PV … no marker so need to calculate

18. Percent Body Water in Various Tissues
Note that due to the low % of water in adipose tissue, total body water varies inversely with adipose tissue
Also note that Body Water % declines from ~75% at birth to 60% by 1 yr, decreases some more in the elderly as lean muscle decreases

19. Terminology - diffusion
Diffusion: the movement of solute from a region of higher concentration to a region of lesser concentration

20. Terminology - osmosis
Osmosis: movement of water across cell membranes from a more dilute solution (= higher water concentration) to more concentrated solution (= lesser water concentration)
osmotic pressure is determined solely by the NUMBER of particles in solution (and NOT by their size, mass or valence)

21. Terminology – osmolarity, osmolality
Osmolarity: molar concentration  number of dissociable particles per mole
Osmolality: number of solute particles added to 1 kg of solvent (water)
osmolality ≈ osmolarity for dilute solutions
osmolaLITY is the preferred term for biological fluids (mOsm/kg H2O) since solvent expands with temperature while mass stays the same, but osmolaRITY is also widely used (e.g., your text)

22. Schematic representation of osmotic water movement generation of osmotic pressure due to solute particles in compartment A
Solute particles create a “suck”, pulling in water
The increase in hydrostatic pressure offsets the osmotic pressure

23. Estimating Plasma Osmolality
plasma osmolality ≈ 2  [Na+]Plasma
more accurate clinical estimate…
plasma osmolality ≈ 2  [Na+]Plasma [glucose]Plasma / [BUN]Plasma /2.8
divisors are needed to convert typical units of mg/dL to mmol/L

24. Measuring Osmolality
Relative to pure water, can accurately measure the degree of:
freezing point depression (i.e., decrease from 0 oC)
boiling point elevation (i.e., increase from 100 oC)
These changes are “colligative properties” which are directly proportional to the NUMBER of solute particles in solution, and NOT type of solute
… reason that solute ethylene glycol is added to car coolant systems, roads are salted, etc.
Refractometers can quickly determine specific gravity, a crude estimate of osmolality (weight of solution ÷ equal volume of dH2O)
normal human plasma = to 1.010
so, slightly heavier than water because of added solutes
urine = to 1.030
~1/4 of plasma – 3-4X plasma
wrestlers cannot wrestle if > 1.020… they are dehydrated

25. Terminology – van’t Hoff equation calculation of osmotic pressure
π = σ(nCRT)
Modified van’t Hoff equation
where:
n = number of dissociable molecules (contrast NaCl with glucose…)
C= total solute concentration in moles/liter
R=gas constant (0.082 atm L/mol oK)
T= temperature in degrees Kelvin (37oC = 310 oK)
… at sea level, 760 mmHg/atm  19.3 mmHg/ mOsm
NOTE: you will not need to calculate π on your exam, but do recognize the variables impacting on it

26. Osmotic Pressure, π
At 37 oC, a 1 mmol/L solution of a non-dissociating solute such as glucose exerts an osmotic pressure of 19.3 mmHg …
Note that what might seem like a relatively insignificant osmolarity difference (e.g., 284 mOsm/L vs. 290 mOsm/L across a cell membrane) is greater than mean arterial pressure!

27. Terminology – effective osmoles
glucose cannot cross most cell membranes without the aid of special transporters, and is therefore an effective osmole
urea, although a solute, freely crosses most cell membranes, and is therefore an ineffective osmole; its   0

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29. Determinant of Fluid Movement Across Cell Membranes
osmotic differences between ICF and ECF
there are no hydrostatic differences
MOST cell membranes are highly permeable to water, so a change in osmolality in either ICF or ECF leads to a rapid movement of water between these 2 compartments
since solutes generally cannot cross cell membranes rapidly, it is typically assumed that water moves and solutes do not

30. Terminology - tonicity
refers to solution’s effect on the volume of a cell
hypotonic solutions cause the cell to swell
hypertonic solutions cause the cell to SHRINK
isotonic solutions do not change the volume of the cell, but do expand the extracellular volume

31. Shifts of Water Between Body Fluid Compartments …Volume and Osmolarity Changes from NORMAL are colored
Increased osmolarity
Decreased Volume
Lost Na+ & H2O
Lost H2O
Lost Na+
Gained Na+ & H2O
Gained Na+
Gained H2O

32. Remember: Na+ content and concentration are NOT the same
… Na+ and water are regulated separately (as discussed in separate lectures)
Figure from S. P. Bagby and W..M. Bennett, Adv. Physiol. Edu, 1998

33. Terminology – oncotic pressure
oncotic pressure: osmotic pressure generated by large molecules (especially proteins) in solution…
≈ mm Hg in plasma, a value that appears small but is a very important braking force (“suck”) limiting fluid movement across capillaries

34. Determinants of Fluid Flow Across Capillaries
hydrostatic pressure, created by pumping of heart and acts to force fluid out of its compartment
oncotic pressure of plasma proteins creating a “suck” to keep the fluid where it is at
permeability
fluid movement = Kf[(Pc - Pi) – σ(πc – πi)]
Kf = filtration coefficient of capillary wall
Pc = hydrostatic pressure in capillary lumen
Pi = hydrostatic pressure of the interstitium
σ = reflection coefficient of proteins across capillary wall
πc = oncotic pressure of the plasma
πi = oncotic pressure of the interstitial fluid
the net fluid movement out of the capillaries is returned to the circulation by the lymph (normally 8-12 L/day)

35. Transepithelial capillary forces

36. fluid movement = Kf[(Pc - Pi) – σ(πc – πi)]
Kf = filtration coefficient of capillary wall
varies among vascular beds… it is 100 X greater in glomeruli than in skeletal muscle
Pc = hydrostatic pressure in capillary lumen
increased by increases in either arterial or venous pressures
increased locally by decreased precapillary arteriolar/sphincter resistance or increase in postcapillary resistance
Pi = hydrostatic pressure of the interstitium
difficult to measure, but in the absence of edema,  0 mm Hg or slightly (-)
σ = reflection coefficient of proteins across capillary wall, determines size of oncotic pressure gradient
varies: liver sinusoids are very permeable to proteins, so plasma oncotic pressure ≈ interstitial oncotic pressure while nearly 1.0 in glomeruli
πc = oncotic pressure of the plasma, ≈ mm Hg
πi = oncotic pressure of the interstitial fluid, created by small amount of protein that does leak out of plasma

37. Causes of Extracellular Edema
increased capillary hydrostatic pressure
excess kidney retention of salt and water
acute or chronic kidney failure
mineralocorticoid excess
high venous pressure
heart failure (e.g., LV failure  lung edema)
venous obstruction
failure of venous pumps
paralysis of muscles
immobilized parts of the body
failure of the venous valves
decreased arteriolar resistance
excessive body heat
insufficiency of the sympathetic nervous system
vasodilator drugs

38. Causes of Extracellular Edema
decreased plasma proteins
loss of protein in the urine (nephrotic syndrome)
loss of protein from denuded skin areas
burns
wounds
failure to produce proteins
liver disease
severe protein or caloric malnutrition

39. Causes of Extracellular Edema
increased capillary permeability
immune reactions that cause release of histamine, etc.
toxins
bacterial infections
vitamin deficiency, especially vitamin C
prolonged ischemia
burns

40. Causes of Extracellular Edema
blockage of lymph return
cancer
infections (e.g., filarial nematodes)
surgery
congenital absence or abnormality of lymphatic vessels

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42. Factors Working to Prevent Extracellular Edema
interstitium normally has low compliance
lymph flow can increase fold
increased amounts of protein poor capillary fluid flow wash out the protein from the interstitial space, thereby decreasing net capillary filtration pressure

43. Causes of Intracellular Edema
Two main causes:
depression of metabolic systems of tissues
lack of adequate nutrition to the cells
cells lack the resources to drive the Na+-K+-ATPase pump, so Na+ accumulates in cells and they expand
WATER FOLLOWS SODIUM INTO THE CELLS

44. Causes of Intracellular Edema
Others:
Too little extracellular Na+ and/or
Too much water

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46. Effects of Intravenous Solutions
isotonic (0.9%) NaCl (= normal saline) increases ECF volume
0.45% NaCl expands both ICF and ECF volumes, with majority of expansion in ECF
3% or 5% NaCl solutions can be administered to expand the ECF volume while shrinking the ICF volume
5% albumin can be administered to expand the plasma volume compartment
5% dextrose (D5W) is equivalent to infusing distilled water and expands total body water… dextrose (= glucose ) is rapidly metabolized to CO2 leaving behind the water