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Fluid Balance: Water/Electrolyte/Acid-Base: To survive, we must maintain a normal balance of extracellular fluid (ECF) and intracellular fluid (ICF). We will discuss three interrelated processes. 1) Fluid balance 2) Electrolyte balance 3) Acid-base balance Introduction: On average, for a 70 kg person (154 pounds) with average body fat, a female is 60% water and the male is 50% water. The females have more adipose tissue, which is 10% water, and the skeletal muscle is 75% water. Males have more muscle mass. ECF: Most of the ECF can be found in the interstitial fluid of the peripheral tissues and plasma. ECF can also be found, to a minor degree, in lymph, cerebrospinal fluid, synovial fluid, serous fluid, aqueous humor, perilymph, and endolymph. The exchange among the subdivisions of the ECF occurs primarily across the endothelial lining of the capillaries. The composition of the ECF varies from region to region. These differences are minor when you compare the ECF to the ICF. ECF and ICF are called fluid compartments because they are very distinct entities. The cell membrane allows each cell to maintain its own environment. The principle ions of the ECF are Na+, Cl- and HCO3-. The ICF contains an abundance of K+, Mg+, and PO43-. You will also find a high concentration of negatively charged proteins. If a cell membrane were totally permeable, the ions would reach equilibrium. But the membrane selects through facilitated diffusion and active transport what ions enter and exit the cell. The differences in ionic concentrations will lend to differences in osmotic concentrations. Basic Concepts in Fluid/Electrolyte Regulation: 1) The ECF, not ICF, is monitored for solute concentration. Specifically, the plasma and cerebrospinal fluid is monitored. 2) No receptors monitor the direct fluid or electrolyte balance. Receptors monitor plasma volume and total osmotic concentrations. 3) Cells move water by a passive process, osmosis. 4) If the dietary gains exceed loss to the environment, electrolyte balance will rise. Regulating Hormones: 1) Antidiuretic Hormone: ADH. The hypothalamus contains osmoregulators that monitors the ECF of the cerebrospinal fluid. The cells are sensitive to subtle changes in the ECF. The hypothalamus secretes ADH, which is stored in the posterior pituitary. ADH has two important functions: a) stimulates water reabsorption into the body by targeting the DCT, and b) increase your thirst and thus increasing your water intake. 2) Aldosterone: this increases Na+ reabsorption into the body. This will increase water reabsorption. Aldosterone is produced by the adrenal cortex and is secreted in response to angiotensin. When there is a drop in plasma volume, there is a drop in blood pressure. JGA releases renin, which activates angiotensin 1, which activates angiotensin 2, which activates aldosterone. The Na+ reabsorption is increased, water follows, and there is an increase in blood volume. 3) Natriuretic Peptides: ANP—oppose the renin-angiotensin system. When plasma volume is too high, the blood pressure is too high. ANP will prevent the release of renin, which will allow more water to be secreted. This will drop blood pressure. Fluid and Electrolyte Balance: Fluid Balance: Water flows freely in ECF compartment. In capillaries, the water is forced out by hydrostatic pressure. Some water is reabsorbed the rest will enter the lymph system. There is also continuous movement within the minor components of the ECF. 1) Water moves across the mesothelial surfaces of serous membranes—peritoneal, pleural, pericardial, synovial…About 7 liters of fluid is produced and reabsorbed each day. The actual volume of present at any one time is about 35 ml. 2) Water moves between blood and cerebrospinal fluid (around the brain and spinal cord0, aqueous humor and vitreous humor (in eye), and the perilymph and endolymph (inner ear). Only small amounts of fluid are found here. Fluid movement in ECF: The largest component of EF is the exchange between plasma and the interstitial fluid, due to hydrostatic pressure. Fluid ends up in the lymph system where it is cleansed and dumped back into the venous system. Any change in pressure will alter the ECF distribution. With an increase in pressure, there is an increase in fluid that will enter the tissue—edema. Pulmonary edema occurs when there is an increase in blood pressure in pulmonary capillaries—forces fluid into the lungs. Fluid Gains and Losses: Water losses: about 2,500 ml of water is lost each day thru urine (1,200 ml), feces (250 ml), perspiration (insensible—water you lose through your skin/respiratory tract without activity— 1,150 ml). Sensible perspiration is perspiration with serious activity, which would increase the amount of water loss to 4 liters/hour. A fever can also cause water loss—for each degree increase in body temperature, you will increase water loss by 200 ml. Water gains: need about 2,500 ml of water each day to balance water loss. You’ll need to gain 1,000 ml through eating, 1,200 ml through drinking, and 300 ml through metabolic generation. Metabolic generation: This is water produced with the conversion of oxygen to water in the electron transport chain. On average, you produce 300 ml of water through metabolic generation. Fluid Shifts: This is a rapid water movement between the ECF and ICF through osmosis. If the solute concentration is high in the ECF, the ECF will by hyperosmotic to the ICF. Water will enter the ECF from the ICF by osmosis. This occurs if you lose water but maintain electrolytes. If the solute concentration of the ECF decreases, the ECF will by hypoosmotic to the ICF. Water moves from the ECF to the ICF. This occurs when you gain water, but no electrolytes. Dehydration: You lose more water than you gain. Water moves from the ICF to ECF. The ICF an ECF will have a higher concentration of solutes than usual. There will be a decrease in both volumes. If left unchecked, it will cause thirst, dryness, headaches, and wrinkly skin. Eventually, the plasma volume will decrease, there will be a decrease in blood pressure, and you will go into shock. This is brought about by excessive perspiration, inadequate water consumption, repeated vomiting and repeated diarrhea. Distribution of Water Gains: With the increase in hypotonic solutions, the ECF will increase in volume and becomes hypoosmotic. Fluid will flow from the ECF to the ICF. Usually, this is corrected by a decrease in ADH, which will increase water loss in the urine. You will also decrease your water intake and increase water output. This is overhydration can affect the central nervous system. The person will act as if drunk—called water intoxication. Electrolyte Balance: this is important for the following reasons: 1) Electrolyte balance affects water balance. 2) Electrolyte concentration can affect cell function. Two cations, Na+ and K+, are of particular interest since they contribute to the osmotic concentration of the ICF and ECF, and they affect the normal functions of the cell. There are two rules about Na+ K+ balance: 1) the most common problems with electrolyte balance are caused by an imbalance between the gains and losses of Na+. 2) Problems with K+ balance is less common, but more dangerous than the Na+ imbalances. Na+ Balance: The total amount of Na+ in ECF represents a balance between: 1) Na+ from the uptake across the digestive epithelium thru facilitated diffusion and diffusion. 2) Na+ excretion at the kidney and other sites (precipitation). A person with Na+ balance usually gains and looses between 1.1 and 3.3 g of Na+ each day. When gains exceed losses, Na+ content of the ECF increases. When the losses exceeds gains, the Na+ content in the ECF decreases. When Na+ increases or decreases, water is gained or lost due to osmosis. The Na+ concentration remains constant. This will either increase or decrease blood/plasma volume, which will increase or decrease blood pressure. If you increase the Na+ intake without adequate water, there will be an increase of Na+ in the ECF, water will leave the ICF and enter the ECF by osmosis. ADH will be secreted (after the hypothalamus picks up the increase of sodium in the cerebrospinal fluid), which will increase water retention and increase your thirst. When Na+ losses exceed gains, the volume of the ECF will decrease. There will be water loss, a decrease in blood/plasma volume and a decrease in blood pressure. If you exercise and only drink water, there will be a decrease of Na+ in the ECF, ADH secretion will decrease, there will be an increase in water loss in the kidney. If there is a significant decrease in blood volume, the renin-angiotensin system will kick in. This will increase Na+ reabsorption; this will cause water to be reabsorbed. If there is too much blood/plasma volume, ANP-BNP is released. This will decrease thirst, blocks ADH and aldosterone—opposes renin. K+ Balance: About 98% of the K+ is in the ICF. Cells use energy to recover K+. Concentration of K+ outside of the cell is very low. The concentration of K+ in the ECF represents a balance of 1) absorption of K+ across the digestive epithelium. 2) The rate of loss in urine. The PCT and CT of the nephron regulate the role of K+ loss. The rate of K+ excretion is related to three functions: 1) Amount of K+ in ECF. If there is a high concentration then more is secreted. 2) Changes in the pH. When the pH of the ECF is low, so is the pH of the peritubular fluid. The rate of K+ loss will decrease, as H+, not K+, is excreted. 3) Aldosterone will exchange K+ and Na+. Na+ in the filtrate is exchanged for K+ in the peritubular capillaries. If K+ decreases, ECF decreases, extensive muscular weakness, eventual paralysis that can be lethal. Other Electrolytes: Calcium Balance: Calcium is the most abundant mineral in the body. You have between 1 and 2 kg of this element. About 99% of the calcium is in the skeleton. In addition to the skeleton, calcium is important for muscle contractions, neural activity, blood clotting, cofactors for enzyme reactions, and secondary messengers. The calcium balance reflects the interplay between calcium reserves in the bone and the rate of absorption across the digestive epithelium, and the rate of loss at the kidneys. The hormones parathyroid hormone (PTH), calcitriol, and calcitonin maintain calcium homeostasis in ECF. PTH and calcitriol increase calcium concentrations and calcitonin will decrease calcium concentration. A small amount of calcium is lost in bile, and usually little calcium is lost in urine or feces. You must absorb about 0.8 and 1.2 g/day of calcium. PTH, from the parathyroid, and calcitriol, from the kidney, will stimulate the DCT and digestive tract cells to increase calcium absorption. Hypercalcemia occurs when you have too much calcium and vitamin D. Symptoms: fatigue, confusion, cardiac arrhythmias, and calcification of the kidneys and soft tissue. Hypocalcemia occurs when there is a decrease in calcium concentration. Vitamin D deficiency or chronic renal failure will cause this disease. Symptoms include muscle spasms, convulsions, osteoporosis, and weak heartbeats. Magnesium Balance: The adult body has about 29 g of magnesium. About 60% of this is found in the skeleton. Magnesium is primarily in the ICF. Magnesium is a cofactor for several important enzyme reactions (including phosphorylization of glucose) and use of ATP by contracting muscle fibers. Magnesium also an important component of bone. PCT reabsorbs magnesium efficiently. The relative low magnesium loss is balanced by the uptake in our digestive system. Phosphate Balance: Phosphate is required for bone mineralization. The most important function of phosphate is in the ICF where it is required for ATP, enzymes, and synthesis of nucleic acids. Phosphate is reabsorbed by the PCT (stimulated by calcitriol) and from the digestive system. It is lost in the urine. Chloride Balance: Chloride is the most abundant anion in the ECF. In ICF the chloride concentration is very low. Chloride is absorbed through the digestive tract, usually with Na+, and reabsorbed in the ascending loop of henle. The rate of chloride loss is very low. You will lose chloride in your urine and sweat. Acid-Base Balance: Introducing acids or bases can change the pH of body fluids. Strong acids or bases dissociate completely in solution, weak acids or bases don’t completely dissociate in solution. A number of molecules will remain intact, for example, a strong acid would be HCl and a weak base would be H2CO3. Why pH control is important: pH of the ECF needs to remain within a narrow limit of 7.35 –7.45. Any change from this can be dangerous. If you change the H+ concentration, you can change the stability of the cell. You cannot survive if you have a pH of less than 6.6 or greater than 7.7. If your pH falls below 7.35, you are in acidosis. If your pH rises above 7.45, you are in alkalosis. With severe acidosis (pH below 7), the CNS will deteriorate (may result in becoming comatose), cardiac contractions are weak and irregular (sign of heart failure), and you blood vessels will dilate (decrease in blood pressure which could result in shock). Although both acidosis and alkalosis are dangerous, acidosis is most common. There are 3 types of acids found in the body: 1) Volatile acids 2) Fixed acids 3) Organic acids 1) Volatile acids: can leave the solution and enter the atmosphere. Carbonic acid is an important volatile acid. CO2 + H2O > H2CO3 > H+ + HCO3-. CO2 combines with H2O to form carbonic acid, which dissociates into H+ and bicarbonate. This reaction occurs spontaneously, but carbonic anhydrase makes the reaction happen quicker. When CO2 concentration increases in the blood, the increase in H+, and the pH decreases. The concentration of CO2 is the most important factor in affecting the pH of body tissues. At the alveoli, the CO2 diffuses into the atmosphere; the pH increases as the H+ decreases. 2) Fixed Acids: these acids do not leave the solution. The kidneys eliminate them; sulfuric acid and phosphoric acid are examples. They are generated in small amounts with the catabolism of amino acids and nucleic acids. 3) Organic Acids: These are participants or by products of aerobic/anaerobic respiration. Lactic acid is a byproduct of anaerobic respiration. Pyruvic acid is a participant in aerobic respiration. Usually, the organic acids are metabolized quickly. However, there are two times when large amounts of organic acids are produced. a) During heavy exercise, there is an increase in lactic acid b) During starvation or excessive lipid catabolism, there is an increase in ketones and organic acids (from the fatty acids of lipids). Mechanisms of pH control: In order to control pH, you must control H+. You gain H+ through the digestive tract and cellular metabolic activity. You lose these at the kidney where you secrete H+ in urine or in the lungs, from H2O from HCO3- and H+. As H+ travels through the body, it must be neutralized to avoid tissue damage. The H+ are temporarily neutralized by buffers, which are compounds that stabilize pH by providing or removing H+. Buffers include weak acids and weak bases. The body has 3 major buffering systems: 1) protein buffer system: regulate the pH of ICF and ECF and they interact with the other two buffering systems, 2) carbonic acid buffer system: the most important buffer in the ECF, and 3) phosphate buffer system: buffer the pH of ICF and urine. Protein Buffer System: depends on ability of amino acids to respond to pH changes by accepting or releasing H+. If pH increases, the carboxyl group (COOH) can dissociate and release a H+. At the normal pH of the body, most of the carboxyl groups of most amino acids have give up their H+. This is why proteins carry a negative charge. There are amino acids with R groups that could donate a H+ (Aspartic acid and Glutamic acid), if the pH goes outside the normal rang. If the pH drops, the COO- and amino group (NH2) can accept H+. This will form COOH and NH3+. This effect is usually limited to a few amino acids, and the first and last amino acid in the peptide chain. There are also R groups (Lysine, Arginine, and Histadine) that can accept H+. Plasma proteins can contribute to buffering the ECF. This fluid contains protein fibers and amino acids that buffer pH. The ICF contains proteins that buffer the cells changes in pH from organic acids—lactic acid and/or pyruvic acid that are involved in the cell’s metabolism. There are also H+ pumps in the cell membrane. These pumps can move H+ in and out of the cell. Hemoglobin Buffer System: RBCs contain carbonic anhydrase and will absorb CO2, which will change into carbonic acid. Carbonic acid dissociates into HCO3-. This will move out of the RBC and into the plasma—this is exchanged for Cl- (known as the chloride shift). The HCO3will absorb the H+ and increase pH. In lungs, the H2CO3 is changed to CO2 and H2O. The CO2 is released into the atmosphere. Phosphate Buffer System: Consists of the anion H2PO4-, which is weak acid (H2PO4- HPO42+ H+) and acts like bicarbonate and is used in the ICF. The HPO42- can form a weak base by binding to Na+ to form Na2HPO4 (sodium monohydrogen phosphate). Maintain Acid-Base Balance: Buffer system can bind to H+, but the system doesn’t eliminate the H+. The H+ is lost by excreting H+ out with urine and can be tied up as H2O in respiration. The maintenance of a balanced pH is done by balancing the gain and loss of H+ can be done by secreting or absorbing H+, which is done by controlling the excretion of acids/bases and the creation of additional buffers. It is a combination of the buffers, the respiratory system, and the renal system that maintains body pH. Respiratory System: Changes in respiratory rate helps stabilize the ECF pH. This system changes the effect of carbonic acid-bicarbonate. When the concentration of CO2 increases, the level of carbonic acid and bicarbonate increases, and the pH decreases. When the concentration of CO2 decreases, the level of carbonic acid-bicarbonate also decreases and the pH increases. Chemoreceptors in the carotid artery, aorta and medulla are sensitive to the level of pH in the ECF and cerebrospinal fluid (CSF), and will increase or decrease the respiratory rate when needed. Renal System: Changes the rate that H+ and HCO3- are excreted or reabsorbed. Under normal conditions, the body will create organic acids each day. This must be balanced by excreting the equal amount of H+. In addition, the kidney assists the lung in getting rid of CO2. H+ are reabsorbed by active transport in the proximal convoluted tubule and distil convoluted tubule. The secretion of H+ continues until the urine reaches a pH of 4.0 – 4.5. At this point, the number of H+ being pumped into the kidney will equal the number of H+ that is being cotransported out of the kidney. The buffers in the urine allow more H+ to be secreted. The buffers are bicarbonate, phosphate buffer, ammonia (a base that absorbs H+. Ammonia is formed when the amino acid glutamine is broken down by glutamase (in the cells of the PCT/DCT). This forms NH3+ and HCO3-. The NH3+ enters the PCT/DCT to absorb H+. The bicarbonate will enter the peritubular capillary to buffer the blood.). What can affect the acid/base balance? Any disorder that affects the circulatory buffers, respiratory system, or renal function. Cardiovascular conditions Conditions affecting the central nervous system, which can affect the respiratory system and cardiovascular reflexes. Respiratory Problems: Respiration Acidosis: Most common type of acid/base imbalance. There is too much CO2 in blood due to hypercapnia, which is an increase in CO2 concentration—hypoventilation. The increase in CO2 in the cerebrospinal fluid will cause you to increase your respiration. If you can’t respond, acidosis occurs, which can be life threatening. Chronic respiratory acidosis will happen with congestive heart failure, pneumothorax, emphysema, or if you stop breathing. There is a need to increase oxygen to the tissues and to get rid of CO2. Respiration Alkalosis: This is uncommon. This is hypocapnia, which is when you have too little CO2 in the blood. This condition is caused by hyperventilation, when there is an increase in pH of the cerebrospinal fluid. In order to take care of this condition, the person needs to breathe in CO2. Metabolic Acidosis: The second most common type of acid/base imbalance. There are three causes of metabolic acidosis: 1) The production of fixed or organic acids. The H+ released from the acids will overwhelm the bicarbonate buffer. The pH will decrease. Here are two examples: a) Lactic acidosis: Too much exercise produces a lot of lactic acid when the muscles rely on anaerobic respiration. b) Ketoacidosis: Produce a lot of ketones and organic acids from the break down of fatty acids when you starve or have diabetes. You can’t use glucose, so you turn to lipids for energy. 2) Unable to excrete H+ from the kidney. This happens when you have kidney damage or take diuretics. The diuretics will turn off the Na+/H+ pump, which pumps H+ into the nephron and Na+ into the peritubular capillary. 3) Metabolic Acidosis: This occurs after severe bicarbonate loss. A decrease in HCO3decreases the ability to remove H+ from the blood. If you have diarrhea you won’t be able to reabsorb HCO3- in the intestine. Metabolic Alkalosis: There is an increase in HCO3- levels. This may be the result of continuous vomiting.