water, fluid, spaces and compartments

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  • 7/29/2019 Water, Fluid, Spaces and Compartments

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    Lecture 7- Water, Fluids, Spaces and Compartments

    1. Internal environment of the human body- Consist largely of water based solutions- A large number of different solutes dissolved in these solutions.- Movement of solutes across cell membrane is influenced by

    Differences in the concentration of various materials across cellmembrane

    Permeability of cell membrane to the materials2. Fluid in the Body

    - 2 primary fluid compartments in the body Intracellular fluid compartments (ICF) Extracellular fluid compartments (ECF)

    Interstitial fluid compartments Intravascular fluid compartment Trans-cellular fluid compartment

    - Volumes of a given compartment is determined by the amount of solutes

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    - 60% of male body weight is water while female with 55% of their body weight is water,Female have fewer percentage of water because they have more fat than man did.

    -

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    - But wait!! How actually we can measure all these volumes in their respectivecompartments?

    Compartment volumes are measured by determining the volume of distributionof a tracer substance. A known amount of a tracer is added to a compartment.

    The tracer concentration in that compartment is measured after allowing

    sufficient time for uniform distribution throughout the compartment. The

    compartment volume is calculated as:

    Volume = Amount of tracer / Concentration of tracer

    Plasma compartments tracers : Evans blue or radio-iodinated serum albumin

    (RISA)

    Measurement of plasma volume requires a tracer which is mostlylimited to this compartment and this is achieved by using a tracer which

    binds to albumin.

    Extracellular compartment tracers : crystalloids(Mannitol or Inulin) and ionics The ionic tracers are small and distribute throughout the ECF but there

    is some entry into cells. ECF will be over-estimated with these tracers

    The crystalloids are larger and less diffusable throughout the ECF. Theydo not enter cells but the lack of full ECF distribution results in a low

    estimate of ECF Total volume tracers : Deuterium oxide or triated water Must measure volumes of interstial (ISF) and intracellular fluid (ICF) indirectly Formulae for Blood Volume

    Blood Volume = Plasma volume x (100/100-Hct)

    Blood Volume = Red cell vol x (100/Hct)

    (where Hct = Haematocrit)

    BV= volume of blood (both red blood cells and plasma) in the circulatorysystem

    Hematocrit : Fraction of the blood that is red blood cells.

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    3. Composition of Fluid compartments

    4. Movements between body fluid compartments

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    - Across the lipid bilayer : main drivers of solute movement between intracellular andinterstitial fluid compartments are OSMOTIC PRESSURE and ELECTROCHEMICAL

    GRADIENTS.

    - Across the capillary wall : main drivers of solute movement between interstitial andplasma compartments are HYDROSTATIC PRESSURE and ONCOTIC PRESSURE.

    - There are many ways of quantifying concentration of a solution : Mass of solute dissolved in a given volume of solution Percent solutions is number of grams of solute in 100ml of solution Molarity (M) = Moles Solute/Solution Volume (L) Molality (m) = Moles Solute/Solvent Mass (Kg) Osmolality (Osm) = Moles Total Solute/Solvent Mass (Kg)

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    - Electrochemical gradient is a separation made by oppositely charged ions by amembrane as generated by actively transporting one or more such ions.- Such gradients are generated via various actions- including sodium-potassium pumps,

    proton pumps etc.

    - They are assimilated as batteries with a voltage created across the membrane.

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    Osmotic pressure is the pressure developed by solutes dissolved in water working across a

    selectively permeable membrane. It is generated by all the dissolved solutes - salts, nutrients,

    proteins - all dissolved solutes.

    Oncotic pressure is Colloid Osmotic Pressure - the part of the osmotic pressure created by the larger

    colloidal solute components. A colloid is where larger particles are suspended in water but they are

    small enough or have features that prevent them from settling out, distinguishing it from a

    suspension). Albumin (protein made by the liver and released into blood) is a colloidal protein that

    generates osmotic pressure and is the plasma component that generates most of the Colloidal

    Osmotic Pressure or Oncotic Pressure of blood, and has the effect of drawing much of the water

    back into the blood from the tissues at the venous end of capillary beds. Without enough albumin in

    blood , the fluid that is forced into the tissues by Blood pressure (Hydrostatic pressure) at the

    arterial end of the capillaries would not be sufficiently drawn back into the blood, the tissues

    become waterlogged and a condition known as edema develops

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    5. Movements between the Intracellular fluid and the Interstitial fluid

    - Cell membrane is impermeable to water and ions- How can other solutes being transported??

    By diffusion By channels

    Small pores that permit water or specific solutes to diffuse throughthem

    By transporters Primary active transporters- also called direct active transport, directly

    uses energy to transport molecules across a membrane

    transmembrane ATPases. A primary ATPase universal to all cellular life is

    the sodium-potassium pump, which helps to maintain the cell potential

    Uniporters : Moves a single solute across the membraneAn integral membrane protein that is involved in facilitated diffusion.

    They can be either a channel or a carrier protein. Uniporter carrier

    proteins work by binding to one molecule of solute at a time and

    transporting it with the solute gradient. Uniporter channels open in

    response to a stimulus and allow the free flow of specific molecules.Uniporters may not utilize energy other than the solute gradient. Thus

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    they may only transport molecules with the solute gradient, and not

    against it.

    Symporters : Moves two or more solutes in the same direction acrossthe membrane

    An integral membrane protein that is involved in movement of two or

    more different molecules or ions across a phospholipid membrane such

    as the plasma membrane in the same direction, and is, therefore, a type

    of cotransporter. Typically, the ion(s) will move down the

    electrochemical gradient, allowing the other molecule(s) to move

    against the concentration gradient. The movement of the ion(s) across

    the membrane is facilitated diffusion, and is coupled with the active

    transport of the molecule(s).

    Antiporter : Moves two or more solutes in opposite directions across themembrane.

    (also called exchanger or counter-transporter) is an integral membrane

    protein involved in secondary active transport of two or more different

    molecules or ions (i.e., solutes) across a phospholipid membrane such as

    the plasma membrane in opposite directions. In secondary active

    transport, one species of solute moves along its electrochemical

    gradient, allowing a different species to move against its own

    electrochemical gradient. This movement is in contrast to primary activetransport, in which all solutes are moved against their concentration

    gradients, fueled by ATP. Transport may involve one or more of each

    type of solute. For example, the Na+/Ca2+ exchanger, used by many

    cells to remove cytoplasmic calcium, exchanges one calcium ion for

    three sodium ions.

    Receptor-mediated endocytosis and transcytosisTranscytosis is the process by which various macromolecules are transported

    across the interior of a cell. Macromolecules are captured in vesicles on one side

    of the cell, drawn across the cell, and ejected on the other side

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    - What about water. How was it being transported? Main driving force for water movement across membrane is osmotic pressure Water requires aquaporin channel proteins to move across membranes The mammalian aquaporins are expressed in various epithelial and endothelial

    cells.

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    - Within the PROXIMAL COLVOLUTED TUBULE reabsorbtion occurs when pH needs to bemaintained and biocarbonate ions are reabsorbed back into the blood stream. Glucose,

    Amino Acids and Potassium Ions are all benefitial for the body so they are actively

    transported into the blood as well. Sodium and Chlorine Ions are also moved back into

    the capillaries so that some salt regulation can occur. On the other end of the scale,

    substances such as hydrogen ions and toxins are actively secreted from the blood into

    the tubule.

    - Within the LOOP OF HENLE, the descending limb allows for the reabsorbtion of waterthrough osmosis whereas the ascending limb allows for the passive and active transport

    of salts such as sodium to move out of the tubules and be reabsorbed.

    - The DISTAL CONVOLUTED TUBULE is where the final adjustments are made to thepassing urine within the tubule systems. This is where highly selective reabsorption

    takes place allowing for small adjustments to be made especially between the presence

    of Potassium and Sodium.

    6. Tonicity

    - Is a measure of the osmotic pressure that a substance can exert across a cell membrane,compared to blood plasma

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    7. Fluid replacement therapyScenario 1 : Addition of isotonic NaCl soln ( 0.9% NaCl, 290 Mosm) to plasma by infusion(the therapeutic introduction of a fluid other than blood, as saline soln into a vein)

    - This cause plasma volume to increase- Interstitial fluid volume increase- ECF volume increase

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    - No change in the osmolality of ECF and ICF compartments ( No. of dissociated particles /mass of H20 )

    Scenario 2 : Addition of hypotonic NaCl solution ( 0.45% NaCl, 145 mOsm) to plasma

    - Plasma volume increase- Interstitial fluid volume increase- Volume of ECF increase

    Scenario 3: Addition of hypertonic NaCl solution (3.0% NaCl, 1000 mOsm) to plasma

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    8. Clinical aspect Dehydration is an ambiguous term that does not distinguish between simple water

    loss and loss of Na+. Both water loss and Na+ loss are associated with a decrease in

    the ECF volume, which is determined by the amount of Na+ in the body and not by

    the Na+ concentration in the plasma.

    due to diarrhea Diarrhea is an increase in the volume of stool or frequency of defecation. It is one of

    the most common clinical signs of gastrointestinal disease,

    The fluid in the bowel is generally considered as part of the transcellularcompartment. Turnover of fluid in the bowel is large. A net amount of about 9 to 10

    liters of fluid enter the gut each day

    About 98% of this fluid is reabsorbed resulting in a faecal water loss of only 200mls/day

    This reabsorption occurs predominantly in the jejunum and ileum. About 1500mls/day enter the colon from the ileum. This means that over a litre per day isabsorbed in the colon.

    The epithelium of the digestive tube is protected from insult by a number ofmechanisms constituting the gastrointestinal barrier, but like many barriers, it

    can be breached. Disruption of the epithelium of the intestine due to microbial

    or viral pathogens is a very common cause of diarrhea in all species. Destruction

    of the epithelium results not only in exudation of serum and blood into the

    lumen but often is associated with widespread destruction of absorptive

    epithelium. In such cases, absorption of water occurs very inefficiently and

    diarrhea results

    The intestinal contents are essentially isotonic by the time the jejunum isreached because water can move into or out of the intestine in response to anyosmotic gradient. Excess loss of intestinal content does not directly cause

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    changes in osmolality of body fluids. As absorption of substances occurs, water

    moves along passively because of the osmotic gradient that is created. The colon

    is involved in reabsorbing water and electrolytes.

    Dehydration due to sweating profuselyCauses of hyperosmotic dehydration include water deficits caused by decreased

    intake, diabetes insipidus, diabetes mellitus, fever (through excessive

    evaporation of the sweat from the skin sweat is hypotonic). Initially, fluid is

    lost from the plasma, which becomes hyperosmotic, causing a fluid shift from

    the interstitial fluid to the plasma. The rise in interstitial fluid osmolality causes

    fluid shift from the ICF to the ECF. Finally, both the ECF and ICF compartments

    are decreased and the osmolality is increased.