Download Water and Electrolyte (Na, K, Cl)

Fluid, Electrolyte Balance & Acid-Base Homeostasis
The body is in constant flux. There is both an intake of food and water which
contain electrolytes such as Na, K, Cl and the body is also losing water and
electrolytes through sweat and urine. What comes in must be excreted if not
needed. Fluid balance refers to the concept that the amount of water gained must
equal the amount lost. The digestive system is the major source of water gain and
the urinary system is the primary system for its removal.
Electrolytes must also be in balance; electrolytes, i.e. the ions released though
dissociation of inorganic compounds must also be balanced. Water and Na
regulation are integrated. This defends the body against disturbances in volume
and osmolarity of fluids. Disturbances in the balance of fluids and electrolytes can
result in dehydration, problems with cardiac and muscle functioning, issues with
exocytosis, muscle contraction, bone formation and clotting.
Fluid and electrolyte balance maintains: volume, osmolarity, ion concentrations
and pH. Fluid/electrolyte balance depends on integration of respiratory,
cardiovascular, renal and behavioral systems. Almost a liter of fluid is lost through
skin, lungs, and feces per day.
Osmolarity
Number of solute particles dissolved in 1liter water. This is reflected in a
solution’s ability to cause osmosis and alter properties of solvent-boiling and
freezing points-osmotic activity. Osmolarity depends only on the number of non
penetrating solute particles-10 Na+ has the same osmotic activity as 10 glucose in
the same amount of fluid. It is important to maintain homeostasis of water which
can cross most membranes freely. If the osmolarity of ECF (extra cellular fluid)
changes then water moves into or out of cells which changes the intracellular
volume. Excess water intakeosmolarity decreaseswater moves into cells
swell. Na intakewater increaseswater moves out of cellsshrink. Changes in
cell volumeimpairs cell function. Swellingion channels openmembrane
permeability changes.
Water Balance
Fluids are the major constituent of the body comprising 55-60% of total body
mass. All cellular operations need water as a diffusion medium and to distribute
gas, nutrients, wastes. Body fluids are found in two major compartments: inside
and outside cells. Intracellular fluid (ICF) comprises 28L; this is the fluid inside
cells or the cytosol. Extracellular fluid (ECF) is the fluid outside of cells and
includes: interstitial fluid-11L and plasma-3L. Two general barriers separate the
intracellular fluid from interstitial fluid and blood plasma. The first is the plasma
membrane which separates intracellular fluid from interstitial fluid and the blood
vessel wall separates the interstitial fluid from blood plasma. The body is in fluid
balance when the required amounts of water and solute are present and correctly
proportional among the various compartments.
Balance is achieved when the fluid gained is equal to the fluid lost. There are a
couple places of fluid gain. The major one comes from consumed food and drink, a
lesser source is metabolic water which is generated by metabolism. Fluid is lost in
four ways: in urine (1.5L/day another), via evaporation of insensible perspiration,
by the lungs and through the GI tract.
Control of Water Balance
Only water lost by urine can be regulated. Body water gain is regulated mainly by
the volume of water intake. Pathological water loss disrupts homeostasis by:
depleting volumedecreases blood volume and pressureBP not maintained
not enough O2 to tissues. Kidneys directly control volume by producing more
concentrated urine or rid excess water by producing urine dilute relative to plasma.
Diuresis is the removal of excess water in dilute urine. The concentration or
osmolarity of urine by kidney is accomplished by varying the amounts of water
and Na reabsorbed by distal regions of nephrons. For dilute urine the kidney
reabsorbs solute without allowing water to follow osmotically. For concentrated
urine the nephron must absorb water and leave solute in lumen.
The high osmotic concentration of the renal medulla’s interstitial fluid allows urine
to become more concentrated. In the PCT reabsorption is isoosmotic. Fluid
entering the Loop of Henle is 300mOSM and the fluid leaving is 100mOSM or
hypoosmotic. Cells in the ascending limb of loop are impermeable to water. When
it pumps Na, K and Cl out of the tubule lumenwater cannot followsolution in
lumen remains hypoosmotic. Once hypoosmotic fluid leaves loop of henle and
passes through the distal segments of nephron, concentration is determined by
permeability of those tubules to water. If not permeablewater remains in
tubuledilute urine. Since some solute is reaborbed in collecting ductsthe most
dilute urine that can be formed is 50mOSM. If permeablewater leaves
tubulewhen collecting duct permeable to waterosmosis draws water out of
lumen into interstitial fluidconcentrated urine-1200mOSM.
Direct control of water excretion in kidneys is exercised by vasopressin-antidiuretic hormone-ADH, a peptide produced by the hypothalamus and stored and
released from the posterior pituitary. When blood fluid osmolarity increases
receptors in the hypothalamus sense increasing plasma osmolarity stimulate
ADH secretion. ADH causes insertion of water channels-aqua porin 2 into
membranes of cells lining collecting ducts, allows water reabsorption to occur.
Water moves out by osmosis because cells and interstitial fluid of medulla more
concentrated than tubule fluid. Without ADH, little water reabsorbed in collecting
ducts-impermeable to waterdilute urine is excreted. Without ADH water pores
are stored in vesicles. With ADH vesicles move to apical membranefuse with
itexocytoisinserts pores into membranecell permeable to water. Intake of
water in response to thirst mechanismsdecreases osmolarity of bloodADH
secretion is shut off and the water channels are removed.
A large decrease in blood volume will also cause ADH release. Decreased blood
volumebaroreceptors in let atrium and in blood vessel wallsADH release.
Severe dehydrate decreases the GFR and as a result blood pressure falls and less
water is lost in urine. An intake of too much water increases blood pressure
increases the GFRinhibits ADH secretion; body wants to rid excess fluid
volume. Body wants to maintain enough volume to generate blood pressure
necessary to deliver blood to tissues. Anything that stimulates ADH secretion also
stimulates thirst.
Sodium Balance
When water loss is greater than water gain the result is dehydration. This results in
an increased osmolarity of body tissues increased osmolarity is noted by
osmoreceptors in the hypothalamus stimulates thirst. Other signals that
stimulate the thirst center are neurons in the mouth that detect dryness and less
saliva production and barorecpetors that detect lowered blood pressure in the heart
and blood vessels. Blood volume decreases which caused a fall in blood pressure.
This stimulates the kidneys to release renin which converts angiotensiongen to
angiotensin I and Ace to convert angiotensin I to angiotensin II.
The elimination of excess body water or solute or the conversion of the same
occurs mainly by control of their loss in the kidney. The extent of urinary salt
(NaCl) loss is the main factor that determines body fluid volume. This is because
water follows solutes in osmosis and the two main solutes in extracellular fluid and
therefore in urine are Na and Cl. Na+ plays a crucial role in water and electrolyte
balance and excitability of neurons and muscle cells. Kidneys regulate Na+ levels.
Na contributes to the osmolarity of body fluids, the amount of solute per unit
volume; this is also tightly regulated. Extreme variation in osmolarity causes cells
to shrink or swell, damaging or destroying cellular structure and disrupting normal
cellular function. Regulation is achieved by balancing intake and excretion of Na
with that of water. Na is the major solute in extracellular fluids and determines
osmolarity of extracellular fluids. Regulation of osmolarity must be integrated with
regulation of volume, changes in water volume alone have diluting or
concentrating effects on fluids. When one is dehydrated one loses proportionately
more water than solute and the osmolarity of body fluids increases. In this situation
body must conserve water but not Na, thus stemming the rise in osmolarity. If you
lose large amount of blood from trauma or surgery, however, your loses of Na and
water are proportionate to composition of bodily fluids. In this situation the body
would conserve both water and Na.
The main factor that determines body fluid osmolarity is the extent of urinary
water loss. Because our diet contains a highly variable amount of NaCl, urinary
excretion of Na and Cl must also vary to maintain homeostasis. Hormones regulate
the urinary loss of these ions which in turn affects blood volume. The three most
important hormones that regulate the extent of renal Na and Cl reabsorption and
therefore how much is lost in the urine are Angiotensin II, ANP and aldosterone.
Angiotensin II and aldosterone promote urinary reabsorption of Na and Cl and
water by osmosis, conserving the volume of body fluids by reducing urinary loss.
An increase in blood volume stretches the atria of the heartANP
releasepromotes natriuresis or elevated urinary excretion of Na and Cl followed
by water excretion which decreases blood volume. An increase in blood volume
slows release of renin from JG cells. With less renin, less angiotensin II is formed
which increases the glomerular filtration rate causing a decrease in Na, Cl and
water reabsorption in the tubules. Less angiotensin II also lowers the levels of
aldosterone. This caused the reabsorption of Na and Cl to slow in the collecting
ductscausing more Na and Cl to be in the tubular fluid and more excreted
therefore in the urine; losing more water in the urine results and this decreases the
blood volume and the blood pressure.
Electrolytes in Body Fluids
Electrolytes dissolve and dissociate and serve four general functions in the body:
they control osmosis of water between fluid compartments, they help maintain
acid-base balance, they carry electrical current and they serve as cofactors. The
electrolyte content of intracellular fluids is different from that of extracellular
fluids. Sodium is the most abundant cation in extracellular fluid and Cl is the most
common anion. Potassium is the most common cation in intracellular fluid and the
most important anions are proteins and HPO4.
Sodium
Sodium accounts for 90% of extracellular cations. It is needed for generation and
conduction of action potentials in nerve and muscle cells. Sodium levels are
controlled by aldosterone, ADH and ANP. When aldosterone increases kidney
reabsorbs Na. During hyponatremia (lowered Na)ADH release stops. This lack
of ADH causes a greater excretion of water in urine and restores the normal Na
level in ECF. ANP causes an increase in Na excretion by the kidneys.
Chloride
Chloride moves easily between extra and intracellular compartments. This is
because most membranes contain Cl leakage channels and antiporters. ADH helps
regulate Cl balance because it governs the extent of water loss in urine. Processes
that increase or decrease the renal absorption of Na also affect the reabsorption of
Cl.
Potassium
Most K is found inside cells. Changes affect resting membrane potentials.
Decreased KhypokalemiaK leaves cells resting membrane potential is more
negative. Increased Khyperkalemiamore K inside celldepolarization.
Hypokalemiam. weakness. More difficult for hyperpolarized neurons and
muscles to fire action potentials-dangerous- respiratory m. and heart m. may fail.
When K moves into or out of cells it is often exchanged for H and therefore helps
to regulate pH levels. Potassium levels are controlled mainly by aldosterone. High
Kmore aldosterone is secretedprinciple cells in renal collecting tubulesK
secretion increases. When K is low aldosterone is secreted lessthere is less K in
urine.
Bicarbonate
Bicarbonate ions increase as blood flows through systemic capillaries because
carbon dioxide is being released by metabolically active cells. They combine with
water to form carbonic acid which dissociates to H and bicarbonate ions. The
kidneys are the main regulators of bicarbonate. Intercalated cells of the renal
tubule can either form bicarbonate or release it into the blood when the blood level
is low or they can excrete it when there is excess in the blood.
Calcium
Calcium is the most abundant mineral in the body since it is stored in bone. In
body fluids it is the primary extracellular cation. Calcium is important in blood
clotting, neurotransmitter release, muscle tone maintenance and nerve and muscle
excitability. The most important regulator is PTH. Low calciumPTH
releaseosteoclasts chew up bonecalcium levels increase. PTH also enhances
reabsorption of Ca from glomerular filtrate and increases calcitriol production
which increases the absorption of calcium from food in the GI tract. Calcitonin
from the thyroid gland inhibits osteoclast activity which accelerates Ca deposition
in bone and lowers blood calcium levels.
Phosphate
85% of phosphate in body is found as CaHPO4 in bone and teeth. Phosphate is an
important intracellular anion. PTH and calcitriol regulate its levels. PTH stimulates
dissolution of bone which release phosphate in blood and it inhibits reabsorption of
phosphate in kidney tubules. Calcitonin promotes absorption by GI tract.
Acid-Base Balance
The maintenance of a pH between 7.35 to 7.45 is a major homeostatic challenge of
the body. This is crucial to normal cellular functions. pH is a measurement of
hydrogen ion concentration of solution. Lower pH indicate higher hydrogen
concentration or higher acidity. Higher pH indicates lower hydrogen concentration
or higher alkalinity. The three d shape of proteins enables them to perform their
functions and this is very sensitive to pH changes. pH changes disrupt stability of
cell membranes, alter protein structure and change enzyme activities. Metabolic
reactions often produce huge excesses of hydrogen ions; without a way to dispose
of this excess the pH would decrease to a lethal level. The body must balance gain
and loss of H ions. Hydrogen ions are gained at the digestive system and through
metabolic activities and are eliminated at the kidneys and the lungs. There are
several ways to ensure pH balance stays normal including chemical buffers and
physiological mechanisms.
Homeostasis of hydrogen is essential to survival and depends on three major
mechanisms: buffers, carbon dioxide exhalation and kidney excretion of H ions.
First defense: Buffering. Second: Respiratory : alteration in arterial pCO2. Third:
Renal : alteration in HCO3- excretion. These systems work together.
Mechanisms of ph Control
Buffers are the first line of defense; they are always present. Most buffers in the
body consists of a weak acid and the salt of that acid which functions as a weak
base. Buffers present a rapid, drastic change in the Ph of body fluids by converting
strong acids and bases into weak and weak bases. The body has a large buffer
capacity. Buffers are dissolved compounds that can provide or remove H to
stabilize pH. They are able to bind or release Hs such that they dampen swings in
pH. Buffer systems do not eliminate H ions; they just make them harmless. They
can be used up. There are three principal buffering systems in the body: protein,
carbonic acid-bicarbonate and phosphate buffering systems.
Protein buffer system- amino acids accept or release H+
 pH: COOH  COO- + H+
 pH: NH2 + H+. NH3+ amino group accepts H
Proteins are composed of an amino acid containing at least one –CooH (carboxyl)
and on –NH2 group (amino group). Hemoglobin is a good buffer found within
RBCs. Albumin is the main protein buffer in blood plasma.
Carbonic Acid-Bicarbonate Buffer System
The carbonic acid-bicarbonate buffer system is the most important extracellular
buffer system. CO2 + H2OH2CO3 . Add H equation shifts to left; more HCO3
is madeincreases CO2 and H2O. The kidneys can make new HCO3 and reabsorb
it. If there is an excess of H, HCO3 can function as a weak base and remove the
excess hydrogen ions. H2CO3 H + HCO3 . This system cannot protect against pH
changes due to respiratory problems in which there is an excel or shortage of
carbon dioxide..
Phosphate Buffer System
The phosphate buffer system is important in buffering ICF and urine. H2PO4H +
HPO4. 2 Na + HPO4Na2HPO4 both reactions are reversible.
Type of Acids in Body
There are two type of acids in the body, volatile which can leave solution and enter
the atmosphere and non-volatile which include fixed and organic acids. Carbonic
acid is a volatile acid. It dissociates to H and HCO3  CO2 + H20. CO2 is the endproduct of complete oxidation of carbohydrates and fatty acids. The amount of
CO2 produced is huge compared to fixed acids production. PCO2 is the most
important factor affecting pH in body tissues.
Fixed acids do not leave solution; they are eliminated at the kidneys, sulfuric and
phosphoric acids are the most important. These are made during catabolism of
amino acids. Organic acids participate in or are end products of aerobic
metabolism. Under severe anaerobic conditionslactic acidlactic acidosis.
Diabetesfats and a. a. metabolized ketoacidsketoacidosis.
Respiratory Compensation
An increase in carbon dioxide in body fluids increases the hydrogen ion
concentration which lowers the pH. Because H2CO3 can be eliminated by exhaling
carbon dioxide, it is called a volatile acid. Changes in respiratory rate directly
affect the carbonic acid-H2CO3 buffer system. Any change in PCO2 affects H and
HCO3. Increasing or decreasing the rate of respiration alters pH by lowering or
raising PCO2. PCO2 increasespH decreases. PCO2 decreasespH increases. As
blood acidity increasespH is lowered and is detected by central chemoreceptors
in the medulla and by peripheral receptors in the aortic and carotid bodiesthis
stimulates the inspiratory center of the medullawhich caused the diaphragm and
other respiratory muscles to contract more forcefully and more frequently
causing more carbon dioxide to be exhaledless H2CO3 formspH increases.
Once blood pH returns to normalhomeostasis is returned. The same negative
feedback regulation occurs when carbon dioxide increases. As carbon dioxide
increasesventilation increasesremoving more carbon dioxidelowers
hydrogen ionreduces pH. If pH increases the respiratory centers are inhibited
which decreases the rate and depth of respiration allowing carbon dioxide to
accumulatehydrogen ions increase and pH decreases.
Renal Compensation
Renal compensation is slower than compensation by buffers or by the lungs.
Metabolic reactions produce nonvolatile acids. The only way to remove these is via
hydrogen ions in the urine. The proximal convoluted tubules and the collecting
ducts of the kidneys secrete hydrogen ions into tubular fluid. In the PCT
sodium/hydrogen ion antiporters secrete hydrogen ions as they reabsorb sodium
ions. Even more important for pH regulation are intercalated cells of the collecting
ducts. The apical membranes of some of these include proton pumps (hydrogen ion
ATPases) that secrete hydrogen ions into the tubular fluid. Intercalated cells can
secrete hydrogen ions against their concentration gradient. HCO3 produced by
dissociation of H2CO3 inside the intercalated cells cross the basolateral membrane
by means of a Cl-/HCO3 antiporter an then diffuse into the peritubular capillaries.
This HCO3 is new.
A second type of intercalated cells has proton pumps in the basolateral membrane.
These secrete HCO3 and reabsorb hydrogen ions. Therefore two types of
intercalated cells help maintain the pH of body fluids by 1) excreting excess
hydrogen ions when pH is low and 2) excreting excess HCO3 when pH is high.
Acid-Base Imbalances
Acidosis or academia is a condition in which the blood pH is below 7.35. Alkalosis
or alkalemia is when blood pH is higher than 7.45. In acidosis, neurons are less
excitableCNS depression confusion & disorientation comadeath. In
alkalosis, neurons become hyperexcitable numbness & tinglingm. twitches
tetanus.
A change in blood pH that leads to acidosis or alkalosis may be countered by
compensation-the physiological response to an acid-base imbalance that acts to
normalize pH. This can be complete or partial. Compensation is accomplished via
the respiratory and the renal systems. Respiratory compensation occurs in minutes
via hyper and hypoventilation. Renal compensation is due to changes in secretion
of hydrogen ions and reabsorption of bicarbonate ions by the kidney tubules. This
may begin in minutes but takes days to be maximally effective.
Respiratory acidosis and alkalosis result from changes in the partial pressure of
carbon dioxide in arterial blood. Metabolic acidosis and alkalosis results from
changes in bicarbonate concentration.
Respiratory Acidosis & Alkalosis
The hallmark of respiratory acidosis is an abnormally high PCO2 in arterial blood.
It develops when respiratory system cannot eliminate all CO2 made by peripheral
tissues. Primary symptom hypercapnia  respiratory acidosis. Inadequate
exhalation of carbon dioxide causes pH to drop. The usual cause is
hypoventilation, low respiratory rate. Conditions such as emphysema, pulmonary
edema and airway obstruction may lead to this. It the problem is not too severe the
kidneys can help raise the pH by increasing the excretion of hydrogen ions and the
reabsorption of bicarbonate ion.
Respiratory alkalosis is uncommon and due to hyperventilation  hypocapnia
(plasma PCO2 decreases) respiratory alkalosis. This can be fixed by breathing
into a paper bag-rebreathe exhaled CO2. Renal compensation may occur with
decreased excretion of hydrogen ions and decreases reabsorption of bicarbonate.
Metabolic Acidosis & Alkalosis
Metabolic acidosis can be due to three factors. The systemic arterial blood
bicarbonate levels may drop causing pH to drop. This can occur due to loss of
bicarbonate due to renal dysfunction or it can be due to lose of bicarbonate
through severe diarrhea. Metabolic acidosis can be due to an accumulation of non-
volatile acids. There are two types- lactic acidosis and ketoacidosis-generation of
large amount of ketone bodies which occurs during starvation. It can also be
caused by impaired ability to excrete H at kidney.
Respiratory compensation is rapid an involved decreased ventilation with less
CO2 blown off increases PCO2increases H and HCO3. Kidneys will excrete H
and reabsorb HCO3.
In metabolic alkalosis, HCO3 levels become elevated. This can be due to a non
respiratory loss of acid or excessive intake of alkaline drugs causing blood pH to
increase. Excessive vomiting causes a loss of HCl. Respiratory compensation may
bring blood pH back to normal with a reduction in breathing rate; there may also
be an increased loss of HCO3 at kidney.