Monday, May 4

Self-study: Homeostasis
Homeostasis maintenance of static or constant conditions
in the internal environment
Body fluid volume and composition are kept
relatively stable during steady state.
Fluid intake is highly variable. Thus, fluid output
must be carefully regulated to match it.
Total body water
~60% of body weight is water
Body water is distributed through body tissues:
o Muscle (43%), skeleton (16%), adipose
(10%), other organs (6%)
The distribution of water within tissues also varies
o Muscle/Organs (75%), skeleton (22%),
adipose (<10%)
There is an inverse relationship of body fat
percentage and total body water percentage

Body Fluid Balance

Intake should equal output
Intake consists of food and drink (~2000 mL/day)
and that generated from oxidative metabolism (~300
mL/day).
Output consists of urine (major), insensible water
loss (perspiration from skin/lung, more in burn
patients; sweat, more with exercise), and feces
(excessive in diarrhea).
The kidney is one of the most important regulatory
organs for fluid and metabolic waste balance.
Kidney Function
A. Basic function
1. Regulate water and inorganic ion balance
2. Remove metabolic waste products via urine
excretion (urea, uric acid, creatinine)
3. Remove foreign chemicals via urine (pesticides,
food additives)
B. Acid base balance
C. Secrete hormones
1. EPO (RBC production)
2. 1,25-dihydroxyvitamin D3 (Ca/Ph balance)
3. RAAS renin (Na balance)
D. Gluconeogenesis (fasting glucose maintenance)
Fluid compartments
A. Living things are open systems (in contact with
external environment; e.g. lung, kidney, GI, skin)
B. Two major fluid compartments

1. Intracellular fluid (ICF) in cells, 40% of BW

(~25L)
a. Composition is similar across all organisms
2. Extracellular fluid (ECF) 20% BW (15L)
a. Plasma fluid in blood vessels (1/4: 3 L)
b. Interstitial fluid (ISF) fluid outside
vessels (3/4: 12 L)
3. 60-40-20 rule
a. 60% total, 40% ICF, 20% ECF (15% ISF,
5% plasma)
C. Blood volume
1. 8% of BW (5 L)
a. 60% plasma, 40% RBC
D. Barriers
1. Capillaries separate plasma from ISF
a. Highly permeable, except to proteins; thus,
plasma is protein rich
2. Cell membrane separate ICF from ECF
a. Semi-permeable
Composition of Body fluids
A. Ionic composition of ECF (plasma and ISF) is
similar since capillary wall is highly permeable
1. Major cation: Na+
2. Major anions: Cl-, HCO33. Protein is impermeable across capillaries more
in plasma
a. Gibbs Donnan effect Na+ is 2% greater in
plasma (vs. ISF) due to negatively charged
proteins; Cl- is lower
B. Ionic composition of ICF
1. Major cations: K+, Mg2+
2. Major anions: proteins, inorganic phosphates
Measurement of body fluid compartments

A. Dilution principle
1. V=Adye/Cfinal
2. Subtract volume of dye injected
B. Measuring plasma volume
1. Probe that avidly binds plasma proteins (e.g.
131
I-albumiin, Evans blue dye)
2. Use same equation from dilution principle
(where V=plasma volume)
3. Blood Volume = PV/(1-Hct)
C. Measure ECF
1. Probe that cannot enter cell (stays in ICF/ECF)
(e.g. inulin, thiosulfate, mannitol, Na+)
2. Same equation (where V = ECF volume)
3. ISF = ECF- PV

4. Correct for urinary excretion of probe by

subtracting excreted probe amount from
injected amount
D. Measure Total Body Water
1. Probe that goes everywhere (e.g. 2H2O, 3H2O,
antipyrene)
2. Same equation, V = TBW
3. ICF = TBW ECF
Factors that determine fluid movement between
compartments
A. Between plasma and IF
1. Capillary filtration
a. Hydrostatic, oncotic pressures
B. Between ICF and ECF
1. Osmosis, based on permeability
a. Water, urea, sodium, glycerol
-Osmosis Net diffusion of water from region of high
water concentration to region of low water concentration
-Osmolarity based on number of particles after a mole of
something dissociates into L
A. Osmolarity of body fluids in different
compartments is the same (overall balance of solute
osmolarities)
B. Impermeable solutes: hypotonic causes RBC
swelling, hypertonic causes RBC shrinking
C. Permeable solutes (urea): things happen.
D. Slowly permeable solutes (glycerol): things happen.
-Osmolality based on number of particles after a mole of
something dissociates into kg
-Osmotic pressure pressure required to prevent the
osmosis; directly proportional to the concentration of
osmotically active particles, not their size
Dehydration
A. Decrease volume, increase osmolarity (normal is
290 mOsm)
Plasma Osmolarity
A. Plasma Osmolarity: (Glc/BUN can normally be
approximated by adding 10; the conversion factors
are for mg/dLmOsm/L)

2. Dehydration due to water deprivation only

water lost, NaCl retained:
a. Give isotonic glucose or hypotonic saline
with glucose
D. Osmolarity Gap difference between osmolarity
and osmolality: there is something making the
difference (EtOH, MeOh, etc.)
1. A gap of >10 is abnormal
2. Method: freezing point depression is preferred
Changes
A. Isosmotic volume expansion
1. Causes: isotonic saline infusion in clinic
2. Increase ECF volume, maintain Osm
3. No change in ICF volume or Osm

B. Hyposmotic volume expansion (gain of water)

1. Causes: SIADH, drinking water, nutritive
glucose soln. infusion
2. Volume increase in all compartments
3. Decrease Osm in all compartments
4. Hematocrit unchanged: RBC concentration
decreases, but cell volume increases
proportionally

C. Hyperosmostic volume expansion (Gain of salt)

1. Causes: dry NaCl consumption, hypernatremia
2. Water shifts from ICF to ECF, resulting in a
higher (but equal) osmolarity for both
3. Plasma protein concentration and hematocrit
both decrease due to increased ECF volume

B. How much to infuse?

1. Use original body weight, calculate TBW
2. Calculate current TBW
3. Find the difference, infuse
C. What to infuse?
1. Water? Saline? Isotonic glucose? Hypotonic
saline with glucose?

D. Hyposmotic volume contraction (Loss of NaCl)

1. Causes: adrenal insufficiency (aldosterone

deficiency, hyponatremia), drinking water after
profuse sweating
2. ECF osmolarity transiently decreases.
3. Water shifts from ECF to ICF.
4. Plasma protein concentration and hematocrit
both increase due to decreased ECF volume
(and increased RBC volume)

E. Infusion of isotonic urea

1. Increase volume of all compartments
2. No change in Osm
3. No change in RBC size

Algorithm for osmotic disturbances

1) Identify any changes occurring in ECF (solute added?
Water lost?)
2) Decide how ECF osmolarity is affected (incr, decr, none)
3) If there is a change, determine if water will shift into or
out of cells to reestablish equilibrium between ECF and ICF
osmolarity. (If no change in ECF osmolarity, a water shift
will not occur. And vice versa.)

Self-study: Renal Function Tests

Mass balance is key.
Total Body
A. Output = Intake + production metabolism

Kidney
B. Input (arterial) = Output (venous, lymph, urine)

Nephron
C. Excretion = Filtration Reabsorption + Secretion

Quantitative Analysis of Renal Function

A. GFR rate of filtration of plasma into Bowmans
capsule of the glomerulus; indicator of renal
function
1. Loss of glomeruli due to sclerosis and
destruction hinders GFR
2. Inulin as a model (not produced, metabolized,
secreted, or reabsorbed; just excreted in urine)
3. GFR = Vurine*Ci,urine/Ci,plasma = clearance (inulin)
B. Clearance rate at which a substance is cleared
from the plasma
C. Renal clearance - volume of plasma that is
completely cleared of a substance by kidneys per
unit time

D. Extraction Ratio percentage of substance removed

from plasma
1. X = [Ax-Vx]/Ax
E. Creatinine is the endogenous indicator of GFR
1. Produced by skeletal muscle metabolism
2. Shows a hyperbolic inverse relationship