Physiology Course: Dr. Velu M. Rachel

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PHYSIOLOGY COURSE

MMP 1215

DR. VELU M. RACHEL


Recap
Con’t …

• ICF: 2/3 of TBW

• ECF: 1/3 of TBW


- Plasma: 20%
- IF: 80%
Body fluid volumes in a healthy 70-kg
adult male
Compartment Volume Subdivisions
Intracellular fluid, ICF (2/3 28 L -
of TBW)
Extracellular fluid, ECF; 14 L 10.5 L
1/3 of TBW (Interstitial fluid)

3.5 L
(Plasma)
Total body water (TBW); 42 L -
60% of body weight
Con’t ...
• In terms of composition, these fluids (ICF, Plasma, IF)
contain electrolytes (ions dissociate) and non-
electrolytes.

 Electrolytes – charged particles


 Cations – positively charged ions
• Na+, K+ , Ca++, H+
 Anions – negatively charged ions
• Cl-, HCO3- , PO43-

 Non-electrolytes - Uncharged
• Proteins, urea, glucose, O2, CO2
Measuring body fluid volumes
• Principe: Indicator-dilution principle
• Method:
1. Administer a known amount (A) of a substance that
will get distributed in a particular body fluid
compartment;

2. Determine the final steady state concentration (C) of


this indicator in blood;

3. Volume of distribution (Vd) of the indicator =


Amount of indicator injected (A)/ Concentration in
blood after mixing (C)
Measuring body fluid volumes

• Example

100 mg of sucrose is injected into a 70 kg man. The


plasma sucrose level after mixing is 0.01 mg/ml. If 5 mg
has been metabolized during this period, then, what is
the ECF volume?
Measuring body fluid volumes
• Solution

 Amount of sucrose injected = 100 mg


 Amount metabolized = 5 mg
 Amount remaining in ECF (A) = 95 mg
 Concentration in plasma after mixing (C) = 0.01 mg/ml
 Thus, volume of distribution (Vd) of sucrose = A / C = 95
mg / 0.01 mg/ml
= 9500 ml = 9.5 L (= ECF volume)
Measuring body fluid volumes
• How would you measure IF volume?

 Cannot be measured; it is calculated (estimated)..


 IF volume = ECF volume – plasma volume

• How would you measure ICF volume?

 Cannot be measured; it is calculated (estimated)..


 ICF volume = Total body water – ECF volume
Measuring body fluid volumes

• Relationship between blood volume and plasma


volume.
• Blood = plasma + cells in blood

• Volume of cells: packed cell volume (PCV)


• PCV is also called hematocrit (Hct)
• Blood volume = plasma volume × 100 / (100 – Hct)
Measuring body fluid volumes

• Example

In a healthy 70 kg adult male, plasma volume


was found to be 3000 ml. Hematocrit was 40%.
Calculate his blood volume?
Measuring body fluid volumes

• Lean body mass (LBM)

 LBM is the fat free mass.


 Total body mass = fat mass + fat free mass.
 Note: the water content of LBM is constant.
 Water content of LBM is constant - 70 ml /100mg
tissue.
Measuring body fluid volumes

• Example
In a healthy adult male weighing 70 kg, total
body water (TBW) was measured to be 42 L.
What is his lean body mass (LBM)? What is his
fat mass?
Measuring body fluid volumes
• Solution

• Given TBW = 42 L
• Assume all this water is in LBM & that fat is water
free.
• We know that water content of LBM is 70 ml/100 g
• Thus, if TBW is 42 L, LBM = 60 kg
• Since he weights 70 kg, his fat mass is 70-60 = 10 kg
Fluid and Electrolytes Regulation (RECAP)
• How does movement from space to space occur?

Simple Diffusion

• Movement of solutes from an area of higher concentration to


an area of lower concentration in a solution and or across a
permeable membrane.

• Characteristics:
 is the only form of transport that is not carrier-mediated.
 occurs down an electrochemical gradient ("downhill").
 does not require metabolic energy and therefore is passive.
Con’t….
Facilitated Diffusion

• It is a transport whereby the molecules move down a


concentration gradient through specific protein channels in the
membrane

• Characteristics of facilitated diffusion


 occurs down an electrochemical gradient ("downhill"), similar to
simple diffusion.
 does not require metabolic energy and therefore is passive.
 is more rapid than simple diffusion.
 is carrier-mediated and therefore exhibits saturation, and
competition.
Con’t….
• Saturation: the transport rate increases as the
concentration of the solute increases, until the
carriers are saturated.

• Competition: structurally related solutes compete for


transport sites on carrier molecules. For example,
galactose is a competitive inhibitor of glucose
transport in the small intestine.
Con’t….

• Example of facilitated diffusion

 Glucose transport in muscle and adipose cells is


"downhill," is carrier-mediated, and is inhibited by
sugars such as galactose; therefore, it is categorized
as facilitated diffusion.
Con’t….
Active transport (1airy)

• Characteristics of primary active transport

 occurs against an electrochemical gradient ("uphill").


 requires direct input of metabolic energy in the form
of adenosine triphosphate (ATP) and therefore is
active.
 is carrier-mediated and therefore exhibits saturation,
and competition.
Con’t….

• Examples of primary active transport

 Na+,K+-ATPase (or Na+-K+ pump) in cell membranes


transports
 Na+ from intracellular to extracellular fluid and K +
from extracellular to intracellular fluid; it maintains
low intracellular [Na +] and high intracellular.
 Both Na+ and K+ are transported against their
electrochemical gradients.
Con’t….

 Energy is provided from the terminal phosphate


bond of ATP.
 The usual stoichiometry is 3 Na +/2 K+.
 Specific inhibitors of Na+, K+-ATPase are the cardiac
glycoside
 drugs ouabain and digitalis.
Con’t….

H+,K+-ATPase (or proton pump) in gastric


parietal cells transports H+ into the lumen of
the stomach against its electrochemical
gradient.
 It is inhibited by omeprazole.
Con’t….
Secondary active transport
• Characteristics of secondary active transport
 The transport of two or more solutes is coupled.
 One of the solutes (usually Nat) is transported
"downhill" and provides energy for the "uphill"
transport of the other solute(s).
 Metabolic energy is not provided directly, but
indirectly from the Na+
gradient that is maintained across cell membranes.
Con’t….
• Thus, inhibition of Na+,K+ -ATPase will decrease
transport of Na + out of the cell, decrease the
transmembrane Na + gradient, and eventually inhibit
secondary active transport.
 If the solutes move in the same direction across the
cell membrane, it is called cotransport, or symport.

Examples are Na+-glucose cotransport in the small


intestine and Na+-K+-2Cl- cotransport in the renal thick
ascending limb.
 If the solutes move in opposite directions across the cell
membranes, it is called countertransport, exchange, or
antiport.

Osmosis
• Osmosis is the flow of water across a semipermeable
membrane from a solution with low solute
concentration to a solution with high solute
concentration.
The osmotic pressure difference across the membrane
causes water to flow from solution 2 (which has no
solute and the lower osmotic pressure) to solution 1
(which has the solute and the higher osmotic pressure).
Con’t….

 If two solutions separated by a semipermeable


membrane have different effective osmotic
pressures, the solution with the higher effective
osmotic pressure is hypertonic and the solution with
the lower effective osmotic pressure is hypotonic.

 Water flows from the hypotonic to the hypertonic


solution.
Con’t….
Osmolarity
• is the concentration of osmotically active particles in a
solution.
• can be calculated using the following equation:
• Osmolarity = g X C

where:
• Osmolarity = concentration of particles (osm/L)
• g = number of particles in solution (osm/mol)
 e.g. , gNaC1 = 2; g Glucose = 1
• C = concentration (mol/L).
Con’t…
• Two solutions that have the same calculated osmolarity
are isosmotic.
• If two solutions have different calculated osmolarities,
the solution with the higher osmolarity is hyperosmotic
and the solution with the lower osmolarity is
hyposmotic.

• Example
What is the osmolarity of a 1 M NaCl solution?
Osmolarity = g X C
= 2 osm/mol X 1 M
= 2 osra/L
Fluid movement between compartment
• Fluid exerts a force (pressure) against the vessels wall; this
causes movement of fluid between compartments.

• Two forces (called Starling Forces) determine this


movement.

• We have:
– The hydrostatic pressure of blood: is the pressure exerted by
blood against the walls of the blood vessels by the pumping
action of the heart.

– The colloid osmotic pressure: is a constant the pressure primarily


produced by circulating albumin in the blood vessels.
Fluid movement between compartment

• Hydrostatic pressure (also known as capillary blood


pressure) is higher than the opposing colloid osmotic
pressure in blood at the arteriolar end of the capillary.

• This pressure (CHP) forces plasma and nutrients out of


the capillaries and into surrounding tissues.

• The colloid osmotic pressure (BCOP) maintains fluid in


the blood vessels.
Fluid movement between compartment

• Thus, fluid and the cellular wastes in tissues enter the


capillaries at the venule end, where the hydrostatic
pressure is less than the osmotic pressure in the
vessel.

• These variation of pressure in the blood vessels


allows some phenomena: Filtration and Reabsorption
Fluid movement between compartment

• Filtration is the process by which CHP squeezes fluid


from the plasma in the blood to the IF surrounding the
tissue cells.
• Net filtration occurs near the arterial end of the
capillary since capillary hydrostatic pressure (35 mmHg)
is greater than blood colloidal osmotic pressure (25
mmHg).

• Reabsorption is the process by which fluid re-enters


capillary when BCOP is greater than CHP.
Fluid movement between compartment

• Net reabsorption occurs near the venous end of the


capillary since BCOP (25 mmHg) is greater than CHP
(18 mmHg).

• The surplus fluid in the interstitial space that is not


returned directly back to the capillaries is drained from
tissues by the lymphatic system, and then re-enters the
vascular system at the subclavian veins
Fluid movement between compartment
Fluid movement between compartment

• Application

• HP is especially important in governing the movement


of water in the nephrons of the kidneys to ensure
proper filtering of the blood to form urine.

• As HP in the kidneys increases, the amount of water


leaving the capillaries also increases, and more urine
filtrate is formed.
Fluid movement between compartment

• Application cont.

• If HP in the kidneys drops too low, as can happen in


dehydration, the functions of the kidneys will be
impaired, and less nitrogenous wastes will be
removed from the bloodstream.

• Extreme dehydration can result in kidney failure.


Fluid movement between compartment
• Application cont.

• Fluid also moves between compartments along an


osmotic gradient (Osmosis).
• For example, if you are sweating, you will lose water
through your skin.
• Sweating depletes your tissues of water and increases
the solute concentration in those tissues. As this
happens, water diffuses from your blood into sweat
glands and surrounding skin tissues that have become
dehydrated because of the osmotic gradient.
Fluid movement between compartments
• Application cont.

• Additionally, as water leaves the blood, it is replaced by


the water in other tissues throughout your body that
are not dehydrated.
• If this continues, dehydration spreads throughout the
body.
• When a dehydrated person drinks water and rehydrates,
the water is redistributed by the same gradient, but in
the opposite direction, replenishing water in all of the
tissues.
END

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