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Transcript
Lec.2
Medical Physiology
Z.H.Kamil
Composition of body fluids
Blood composition depends on three major factors: diet, cellular metabolism, and
urine output. In general, the kidneys have four major roles to play, which help keep
the blood composition relatively constant. These are:
1. Excretion of nitrogen-containing wastes.
2. Maintaining water.
3. Maintaining electrolyte balance of the blood.
4. Ensuring proper blood pH.
Fluid and electrolyte homeostasis occurs when fluid and electrolyte balance is
maintained within narrow limits despite a wide variation in dietary intake, metabolic
rate, and kidney function. Body fluids are composed primarily of water and
electrolytes. An electrolyte is a substance that develops an electrical charge (ion)
when dissolved in water. Those substances that develop a positive electrical charge
are called cations (i.e., potassium, K+; sodium, Na+; calcium, Ca++; and magnesium,
Mg++). Electrolytes that develop a negative charge are called anions (i.e., chloride,
CI-, and bicarbonate, HC03-). Electrolytes are regulated by intake, output, acid-base
balance, hormonal influence, and cellular integrity. Non electrolytes are small solute
particles that do not carry an electrical charge when dissolved in water. Examples are
simple sugars (i.e., glucose), proteins, oxygen, carbon dioxide, and organic acids.
Total body water
Water constitutes approximately 65% to 80% of body weight. Total body water
(TBW) varies from person to person and is dependent on several factors:
1. age
2. gender
3. skeletal muscle mass
4. fat content
The water content of adipose tissue is approximately 10% as compared with a water
content of 73% in lean body tissues. Thus the amount of fat in the body determines,
to a major degree, the amount of water. As the infant and child mature, TBW, as a
percentage of body weight, changes. During the first year of life, the total body fluid
percentage decreases, with the most rapid change occurring in the first 6 months.
TBW accounts for 75% 80% of body weight in the newborn, 70% at 6 months, and
65% at 1 year of age. In children, the percentage of total weight as body water
decreases steadily until the adult percentage (55% to 60%) is reached at about 8 years
of age.
In healthy young adult, water probably is half or more of body weight—50 percent in
females and about 60 percent in males. These differences reflect the fact that females
have relatively less muscle and a larger amount of body fat ( fat contains the least
water). Water is the universal body solvent within which all solutes (including the
very important electrolytes) are Dissolved.
TBW is distributed in two separate compartments: the intracellular fluid (ICF)
compartment and the extracellular fluid (ECF) compartment (Fig. 1).
Intracellular Compartment. ICF consists of all liquid within the cell membranes of
the body and is the largest fluid compartment, accounting for 40% of the body
weight. Much of the ICF compartment is found within muscle cells. The primary
electrolytes of the ICF compartment are potassium and phosphate. The ICF
compartment contains only small quantities of sodium and chloride ions and almost
no calcium ions. The cells contain 4 times as much protein as the plasma.
Extracellular Compartment. The extracellular compartment is not a homogenous
compartment. It is composed of interstitial fluid (ISF), plasma, and transcellular
water (TSW). The lSF bathes all of the body cells and includes lymph fluid, the
largest component of ECF compartment. ISF volume accounts for approximately
20% of TBW. Plasma is the liquid component of whole blood, contained within the
vascular system. Although plasma accounts for only 8% of TBW, it is essential to the
functioning of the cardiovascular system. TSW is composed of the fluids found in
pleural, pericardial, synovial, peritoneal, and joint spaces. In addition, TSW includes
the secretions of the salivary glands and pancreas and fluid in the respiratory and
gastrointestinal tracts. The function of TSW is to either lubricate or cushion. TSW
accounts for a small portion of TBW; however, it can increase during certain disease
states.
The serum or plasma portion of the extracellular compartment contains the
electrolytes found in the ECF compartment and a large amount of protein. The
plasma proteins determine colloid osmotic (oncotic) pressure, with the most abundant
plasma protein being albumin. Albumin, because of its size, remains in the vascular
space and exerts a differential osmotic pressure between the capillary lumen and the
interstitial space. The consequence is maintenance of volume in the intravascular
space. Oncotic pressure is also important in the kidney, influencing filtration and
reabsorption of water and solutes. The ECF compartment contains large quantities of
sodium and chloride ions; reasonably large quantities of bicarbonate ion; and small
quantities of potassium, calcium, magnesium, phosphate, sulfate, and organic acid
ions. The ECF compartment makes up just 20% of body weight in the adult.
Regulation of Water and Electrolyte Balance
A dynamic relationship exists between the extracellular and intracellular fluid
compartments. This relationship maintains cellular homeostasis through the exchange
of fluids and electrolytes. The compartments are kept separate by the structural and
functional integrity of cell membranes. Both passive and active processes regulate the
movement of water and solutes across the cell membrane. The selective permeability
of the cell membrane and the specific active transport activity of the cell determine
the characteristics of intracellular and extracellular fluid compartments. A profound
alteration in anyone of the fluid compartments can disrupt cellular health and may
result in a fatal systemic response.
Most water intake is a result of fluids and foods ingested in diet. However, a small
amount (about 10 percent) is produced during cellular metabolism.
There are several routes for water to leave the body:
1. Some water vaporizes out of the lungs.
2. Some water is lost in perspiration.
3. Some water leaves the body in the stool.
If large amounts of water are lost in other ways, the kidneys is putting out less urine
to conserve body water. On the other hand, when water intake is excessive, the
kidneys excrete generous amounts of urine.
Electrolytes such as sodium, potassium, and calcium ions, are also vitally important
to overall body homeostasis, and water and electrolyte balance are tightly linked as
the kidneys continuously process the blood. Very small changes in electrolyte
balance, the solute concentrations in the various fluid compartments, cause water to
move from one compartment to another. Not only does this alter blood volume and
blood pressure, but it can also severely impair the activity of irritable cells like nerve
and muscle cells. For example, a deficit of sodium ions (Na+) in the ECF results in
water loss from the bloodstream into the tissue spaces (edema) and muscular
weakness.
Most electrolytes enter the body in foods and mineral-rich water. Although very
small amounts are lost in perspiration and in feces, the major factor regulating the
electrolyte composition of body fluids is the kidneys.
Movement of Fluids and Electrolytes
For water and electrolytes to function effectively in the body, a regulatory process
that controls fluid movement is required. The regulatory process is dependent on the
concentration of the specific fluid or electrolyte (osmolality) and on the functioning
capacity of the renal system. Fluids move constantly from one body compartment to
another and then remain in specific compartments until an inequality in concentration
of electrolytes develops. Then, movement once again occurs. Movement is through
one of four transport mechanisms: osmosis, diffusion, filtration, and active transport.
Osmosis is the movement of water through a semipermeable membrane from an area
of lower solute content to an area of higher solute activity (with lower activity of
water molecules). Osmosis occurs only when the membrane is more permeable to
water than solutes. The force of the movement, or shift, of water depends on serum
osmolality, which controls distribution and movement of water between
compartments.
Normally, the amount of water that diffuses in and out of the cell is balanced, and the
volumes within the extracellular and intracellular fluid compartments remain
constant. Because water moves freely between the blood, ISF, and tissues, changes in
the osmolality of one body compartment produce a shift in all other compartments.
Consequently, in most cases, the osmolality of the plasma is equal to the osmolality
of other compartments.
Diffusion is the movement of a substance (electrolytes and non electrolytes) from an
area of higher concentration to one of lower concentration through a solution or gas.
Diffusion ceases when equilibrium occurs.
Electrical potential differences and pressure differences across the pores of a
semipermeable membrane also influence diffusion, although the most important
factor determining the rate of diffusion is the concentration difference. The greater
the concentration difference, the greater the rate of diffusion.
Molecules moving via simple diffusion must possess one of two capabilities: lipid
solubility or a negative charge. The lipid-soluble molecules, such as oxygen, carbon
dioxide, and alcohol, are able to diffuse readily through the lipid component of the
cell membrane. Chloride is an example of a negatively charged particle able to pass
easily through the membrane pores.
Filtration is the transfer of water and dissolved substances through a semipermeable
membrane from a region of high pressure to a region of low pressure. The force
causing filtration is hydrostatic pressure. An example of filtration is the passage of
water and electrolytes from the arterial capillary bed to the ISF in response to blood
pressure. The pumping action of the heart causes the hydrostatic pressure.
Movement against a concentration or electrochemical gradient is known as active
transport, and energy, in the form of adenosine triphosphatase (ATPase), is required
for the activity . The transport occurs somewhat like a "pump" in the membrane of
the cell, driven by the energy generated by cellular respiration. Regulation and
distribution of sodium and potassium within the interstitial and the intracellular fluid
compartments are via the sodiumpotassium pump. Active transport is necessary to
move sodium from the cells to the ECF compartment. The active process of pumping
sodium out of the cells forces potassium into the cell.
Not only is energy required to move substances against a concentration gradient, but
a carrier substance is required for the transport of sodium, potassium, chloride,
sugars, and amino acids. Carrier substances are either a protein or a lipoprotein. The
protein carriers function by providing an attachment site for the specific substance to
be transported. The lipoprotein facilitates the solubility of the substance in the lipid
portion of the cell membrane.
Reabsorption of water and electrolytes by the kidneys is regulated primarily by
hormones:
1.
Highly sensitive cells in the hypothalamus called osmo-receptors react to
the change in blood composition by becoming more active. The result is that
nerve impulses are sent to the posterior pituitary which then releases antidiuretic hormone (ADH), this hormone prevents excessive water loss in the urine.
As more water is returned to the bloodstream, blood volume and blood pressure
increase to normal levels, and only a small amount of very concentrated urine is
formed. ADH is released more or less continuously unless the solute concentration
of the blood drops too low. When this happens, the osmoreceptors become
"quiet," and excess water is allowed to leave the body in the urine.
2.
Aldosterone is the major factor regulating Na+ content of the ECF and in
the process helps regulate the concentration of other ions (Cl-, K+, and Mg2+ as
well. Na+ is the electrolyte most responsible for osmotic water flows.
Consequently, water leaves the bloodstream and flows out into the tissue spaces,
causing edema and possibly a shutdown of the circulatory system. When
aldosterone concentrations are high, most of the remaining Na+ are reabsorbed.
Generally each Na+ reabsorbed, Cl- follows and K+ is secreted into the nitrate.
Thus, as the sodium content of the blood increases, potassium concentration
decreases, bringing these two ions back to their normal balance in the blood.
Still another effect of aldosterone is to increase water reabsorption.
Aldosterone is produced by the adrenal cortex. Although rising potassium levels or
falling sodium levels in the ECF directly stimulate the adrenal cells to release
aldosterone, the most important trigger for aldosterone release is the reninangiotensin mechanism. Renin catalyzes the series of reactions that produce
angiotensin II, which in turn acts directly on the blood vessels to cause
vasoconstriction and on the adrenal cortical cells to promote aldosterone release.
As a result, blood volume and blood pressure increase. The renin-angiotensin
mechanism is extremely important for regulating blood pressure.
Maintaining Acid-Base Balance of Blood
Blood pH must be maintained between 7.35 and 7.45, a very narrow range.
Whenever the pH of arterial blood rises above 7.45, a person is said to have
alkalosis. A drop in arterial pH to below 7.35 results in acidosis.
Although small amounts of acidic substances enter the body in ingested foods,
most hydrogen ions originate as by-products of cellular metabolism, which
continuously adds substances to the blood that tend to disturb its acid-base
balance.
Many different acids are produced (for example, phosphoric acid, lactic acid, and
many types of fatty acids). In addition, carbon dioxide, which is released during
energy production, forms carbonic acid. Ammonia and other basic substances are
also released to the blood as cells go about their usual function.
Blood Buffers
Chemical buffers are systems of one or two molecules that act to prevent
dramatic changes in hydrogen ion (H+) concentration when acids or bases are
added. They do this by binding to hydrogen ions whenever the pH drops and by
releasing hydrogen ions when the pH rises.
-Strong acids dissociate completely and liberate all their H+ in water. Consequently they can cause large changes in pH.
-Weak acids like carbonic acid dissociate only partially and so have a much
slighter effect on a solution's pH.
However, weak acids are very effective at preventing pH changes since they are
forced to dissociate and release more H+ when the pH rises over the desirable pH
range. This feature allows them to play a very important role in the chemical buffer
systems.
-Strong bases like hydroxides dissociate easily in water and quickly tie up H+.
-weak bases like bicarbonate ion (HCO3-) and ammonia (NH3) are slower to accept
H+. However, as pH drops, the weak bases become "stronger" and begin to tie up
more hydrogen ions. Thus, like weak acids, they are valuable members of the
chemical buffer systems.
The three major chemical buffer systems of the body are the bicarbonate,
phosphate, and protein buffer systems.
The bicarbonate buffer system is a mixture of carbonic acid (H2CO3) and its salt,
sodium bicarbonate (NaHCO3). Since carbonic acid is a weak acid, it does not
dissociate much in neutral or acidic solutions. Thus, when a strong acid, such as
hydrochloric acid (HCl) is added, most of the carbonic acid remains intact.
However, the bicarbonate ions (HCO3-) of the salt act as bases to tie up the H +
released by the stronger acid, forming more carbonic acid.
Similarly, if a strong base like sodium hydroxide (NaOH) is added to a solution
containing the bicarbonate buffer system, NaHCO3 will not dissociate further under
such alkaline conditions. However, carbonic acid will be forced to dissociate further
by the presence of the strong base—liberating more H+ to bind with the OHreleased by NaOH.
The net result is replacement of a strong base by a weak one, so that the pH of the
solution rises very little.
Respiratory System Controls
the respiratory system eliminates carbon dioxide from the blood while it "loads"
oxygen into the blood. When carbon dioxide (CO2) enters the blood from the
tissue cells, most of it enters the red blood cells where it is converted to
bicarbonate ion (HCO3-) for transport in the plasma.
Under normal conditions, the hydrogen ions produced by carbon dioxide
transport have essentially no effect on blood pH. However, when CO2
accumulates in the blood or more H+ is released to the blood by metabolic
processes, the chemoreceptors in the respiratory control centers of the brain (or in
peripheral blood vessels) are activated. As a result, breathing rate and depth
increase, and the excess H+ is "blown off" as more CO2 is removed from the
blood.
On the other hand, when blood pH begins to rise (alkalosis), the respiratory
center is depressed. Consequently, the respiratory rate and depth fall, allowing
carbon dioxide (hence, H+) to accumulate in the blood.