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Dr. Ngadikun, M.Biomed.

Department of Biochemistry,
Faculty of Medicine, Public Health and Nursing
Universitas Gadjah Mada
Outlines
I. INTRODUCTION
II. DEFINITION
III.VOLUMES OF BODY FLUID
COMPARTMENT
IV.DYNAMIC EQUILIBRUM
(HOMEOSTASIS)
V. KIDNEYS PLAYS IN HUMAN
OSMOREGULATION BY ADH
VI.CLINICAL EXAMPLES
I. INTRODUCTION

The blood vasculature supplies tissues with nutrients, clears


waste products.
Vascular permeability is important for maintaining homeostasis
II. DEFINITION
Fluid
Solution,
Diffusion,
Compartment
Transport of substance (solute, solvent)
Osmosis, osmotic pressure
osmole, osmolality, osmolarity
18 g H2O  6.02 x 1023 molecules
The osmolarity of solution containing a 1M solution of sucrose is 1x1 = 1 osmol/L.
The osmolarity of solution containing a 1M solution of NaCl is: 1x2 = 2 osmol/L;
The osmolarity of solution containing a 1M solution of CaCl2 is 1x3 = 3 osmol/L.
The osmolarity of solution containing a 1M solution of sucrose is 1x1 = 1 osmol/L.
(This equation can be also used to calculate the osmolarity of solutions whose
solutes that do not dissociate such as sucrose, glucose, urea, glycerol, .... Their
osmolarity equals their molarity because n=1).
If a solution contains MANY different type of solutes (for example: BOTH glucose
and sodium chloride are in the solution), its osmolarity can be calculated from the
following equation:
Osmolarity = SUM OF ALL (molarity x n) OF EACH SOLUTE
n: number of particles that dissociated from the solute molecule.
The osmolarity of solution containing 1M solution of NaCl AND 1M solution of CaCl2
AND 1M solution of sucrose is 6 osmol/L
Normal plasma osmolality
Plasma solutes, millimoles/liter
Cations Anions
Na+ 135 Cl- 108
K+ 3.5 HCO3- 24
Ca++ 2 Lactate 1
Sum 140.5 Albumin 0.6
Sum 133.6
Glucose 5
Urea 5
Grand total 284.1

Normal plasma osmolality = 285 to 310 mOsm/liter


Tonicity

Solutions can also be classified by their tonicity


= whether solutions will cause a change in cell
volume

Isotonic : same tonicity as normal interstitial fluid


hypertonic : greater than normal tonicity
hypotonic : lower than normal tonicity
Examples:

Isotonic Saline = 300 mOsmolar = 150 millimolar


= 0.15 moles x 58.5 g/mole
= 8.8 g/liter = 0.88% solution
(usually rounded to 0.9% NaCl)

Isotonic Glucose = 300 mOsmolar = 300 millimolar


= 0.30 moles x 180 g/mole
= 54 g/liter = 5.4% solution
(usually rounded to 5% glucose)

5 mOsmole glucose =
5 x 180 mg/L = 900 mg/L = 90mg%
III. VOLUMES OF BODY FLUID
COMPARTMENT
 fluid continually exchanged between compartments
 water moves by osmosis. if imbalance arises, osmosis restores
balance within seconds so the intracellular and extracellular
osmolarity are equal
 Electrolytes play the principal role in governing the body’s water
distribution and total water content
COMPOSITION OF ICF & ECF

Height of left half of each


column indicates total
concentration of cations;
that of right half,
concentration of anions.
Both are expressed in
milliequivalents per liter
(meq L–1) of water. Note
that chloride and sodium
values in cell fluid are
questioned. It is probable
that, at least in muscle, the
intracellular phase contains
some sodium but no
chloride. Adapted from
Gregersen, M. I. In: P. Bard
(Ed.), Medical Physiology,
11th ed. St. Louis, MO:
Mosby, 1961, p. 307.
IV. DYNAMIC EQUILIBRUM
(HOMEOSTASIS)
Transport of substance
Movement of Solvent and Solute Between the
Plasma and Interstitial Fluid

The distribution of fluid between plasma and interstitium depends on:


1. Capillary hydrostatic pressure (Pc)
2. Osmotic/oncotic pressure due to plasma proteins (πc )
3. Interstitial fluid hydrostatic pressure (Pi)
4. Osmotic pressure due to proteins in interstitial fluid (πi )

Imbalances in these factors edema & decrease blood volume.


Hydrostatic pressure : by heart systolic force 
pushes water out of the capillaries

Osmotic pressure: pressure required to prevent


the osmosis
proportional to the concentration of
osmotically active particles

Colloid osmotic pressure = Oncotic pressure 


Protein  colloid & big molecules

pressure drives water back into the vessels.


Movement of Solvent

Starling forces
Movement of Solute

A total of 8 species (GLC, LAC, PYR, ALA, FFA, GLR, CO2 and O2) undergo blood-tissue cells
exchange; 10 species (PYR, FAC, CoA, NADH, NAD+, ATP, ADP, Pi, CO2 and O2) exist in both
the cytosolic and mitochondrial domains with a negligible transport flux (Jcyt«mit,j  0).
V. KIDNEYS PLAYS IN HUMAN
OSMOREGULATION
Higher osmolality than normal levels may be due to:
= Dehydration
= Diabetes insipidus
= Hyperglycemia
= Hypernatremia
= Methanol poisoning
= Stroke/head trauma deficient ADH secretion
= Uremia

Lower osmolality than normal levels may be due to:


= Excess fluid intake
= Hyponatremia
= Overhydration
= Syndrome of inappropriate ADH secretion
Aldosterone
ADH (vasopressin)
increased osmolality in the blood 
- stimulate secretion ADH 
- increased water reabsorption
- more concentrated urine

decrease osmolality in the blood 


- suppress release ADH
- decreased water reabsorption
- increase urine

Increase only 2% - 3% plasma osmolality =


Change 10% -15% blood volume 
response strong desire to drink
ANH: atrial natriuretic hormone

ANH-induced action in medullary collecting duct cells. Urinary ANH binds to its receptor NPR-A and thereby induces the
conversion of GTP to cGMP. cGMP inhibits apically sodium entry through the cyclic nucleotide-gated channels (CNG), the
heteromeric channel of transient receptor potential V4 (TRPV4) and -P2 (TRPP2), and basolaterally through the Na-K-
ATPase (NKA) and thereby promoting natriuresis.
VI. CLINICAL EXAMPLES

1. Drowning in salt vs fresh water:

Autopsy:
Hypertonic sea  shrunken lung cells
Hypotonic fresh water  swollen lung cells

2. Stroke:
- Accumulation of interstitial fluid in the brain
- BBB impermeable to most substance
- Excess fluid in brain tissue can be removed by
imposing an osmotic gradients (Mannitol)
Two solutions:
- 300 mOsm/L of urea
- 300 mOsm/L of sucrose

Blood placed in the two


solution 

a. In urea solution  swell


 burst (permeable)
a. b.
b. In sucrose solution 
volume of blood cell is
not change (impermeable)
Hypertonic
Hypotonic
REFERENCES
1. Dash RK, et al. (2008) Metabolic Dynamics in Skeletal
Muscle during Acute Reduction in Blood Flow and Oxygen
Supply to Mitochondria: In-Silico Studies Using a Multi-
Scale, Top-Down Integrated Model. PLoS ONE 3(9):
e3168.
2. Devlin TM. 1997. Textbook of Biochemistry with Clinical
Correlations. 4th Ed. John Wiley & Sons Inc. New York.
3. Murray RK, Bender DA, Botham KM, Kennelly PJ, Rodwell
VW, Weil PA. 2012. Harper’s Illustrated Biochemistry 29th
Ed. McGraw Hill Companies Inc., USA.
4. Theilig F and Wu Q. ANP-induced signaling cascade and
its implications in renal pathophysiology. Am J Physiol
Renal Physiol 308: F1047 – F1055, 2015.

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