Biol 224 Chapter 27 Fluid, electrolytes and acid-base balance

Body water loss (4)

- Each day, about 300 ml will be lost as we exhale in the form of water vapor - On average, we will lose 600 ml/day in the form of perspiration Is roughly 400 ml/day as insensible perspiration and 200 ml/day as sweat About 100 ml/day is lost in feces The kidneys will excrete ~1500 of fluid in the form of urine - The amount of water loss through a given route can vary greatly as conditions change For example, strenuous exercise will greatly increase losses through perspiration If you have a GI infection, you may lose liters as diarrhea

Body water gain

- Ingestion of liquids and moist foods account for most of the bodies gain in water About 1600 ml/day from liquids and 700 ml/day from food, = ~2300 ml/day - The other source of water for the body is water produced from metabolic reactions, called metabolic water About 200 ml/day are generated from metabolic reactions Most of this water is from aerobic respiration, when electrons and protons combine with oxygen to form water The rest comes from dehydration synthesis reactions that produce water

Regulation of water and solute loss (salt intake)

- Loss of water and solutes through sweating and exhalation will increase during exercise - However, the majority of the elimination of excess body water and solutes will occur mainly via urine - The extent of urinary salt (NaCl) loss is the main factor that determines body fluid volume This is because WATER FOLLOWS SOLUTES during osmosis, and the main solutes in extracellular fluid and urine are sodium and chloride ions - Our diets are highly variable in the amount of salt intake Urinary output must also vary to maintain homeostasis - When we ingest a salty meal, the plasma levels of Na+ and Cl- increase This leads to an increase in osmolarity of the interstitial fluid The increase in blood plasma and interstitial fluid osmolarity result in the movement of water from intracellular fluid into the interstitial fluid, and then into the blood plasma This increases the blood volume and blood pressure

Sodium

- Sodium ions are the most abundant ions in extracellular fluid Account for 90% of the cations - Functionally, Na+ plays a pivotal role in fluid electrolyte balance, as it accounts for almost half of the osmolarity of the extracellular fluid The movement of Na+ through voltage gated channels is also critical for generation and conduction of action potentials

Dehydration (cont.)

- Stimulation of the thirst center results in the sensation of thirst This is usually followed by an increase in fluid consumption and restoration of fluid balance - Sometimes the thirst sensation is slow to develop, or water is restricted, and significant dehydration occurs It is wise to start replacing fluids when diarrhea or vomiting is occurring before the thirst sensation develops

Barriers that separate intracellular and extracellular fluid

- The plasma membrane is a selectively permeable membrane Allows certain molecules to pass through it, while impeding others Contains active transport pumps to maintain differential concentrations of ions in the cytosol and interstitial fluid - Blood vessel walls divide the blood plasma from the interstitial fluid Only in capillaries are the walls thin enough to allow exchange of water and solutes between blood plasma and interstitial fluid

Electrolytes dissolve and dissociate into ions, that serve 4 general body functions

- They control the osmosis of water between fluid compartments This is possible because they are usually confined to certain compartments - They maintain the acid-base balance needed for normal cellular activities The many proteins of the body only function in a particular pH range - They carry electrical current This allows for the generation of both graded and action potentials - They serve as cofactors for many enzymes

Acid base imbalance

A change in blood pH that results in acidosis or alkalosis may be countered by compensation, the physiological response to an acid-base imbalance These can be either complete, restoring normal pH, or incomplete, where pH is closer to normal, but still outside of the normal range If the altered blood pH is due to metabolic causes, hyperventilation or hypoventilation can bring the pH back to normal This is called respiratory compensation If the altered blood pH is due to respiratory problems, renal compensation can help reverse the condition This is the excretion of H+ and reabsorption of HCO3-

Intracellular fluid

About 2/3 of the fluid is intracellular fluid This is contained in the cytosol of cells

Phosphate

About 85% of the phosphate in adults in stored as calcium phosphate salts in the bones and teeth - The remaining 15% is ionized, typically as three phosphate ions, H2PO4-, HPO42- and PO43- At the normal pH of body fluids, HPO42- is the most common form - Phosphates are an important buffer of H+ in both body fluids and urine While some are free, most are covalently bound to organic molecules (proteins, lipids, nucleic acids) - Parathyroid hormone (PTH) stimulation of osteocytes will increase phosphate release from bone However, in the kidneys, PTH will inhibit reabsorption of phosphate, lowering blood phosphate levels Calcitriol promotes absorption of phosphate in the GI tract Fibroblast growth factor 23 is a polypeptide paracrine (locally acting) hormone that decreases phosphate levels by increasing excretion in the kidneys and decreasing absorption in the GI tract

Atrial natriuretic peptide (ANP)

After finishing a mega super thirst buster (or whatever they call them now), the increase in fluid will results in blood volume increasing Increased blood volume results in ANP production ANP causes natriuresis, elevated excretion of Na+ and Cl- In turn more water is excreted, and blood volume decreases

Alkalosis

Alkalosis is a condition where blood pH rises above 7.45 This condition can result in over-excitability of the CNS and peripheral nerves The nerves conduct signals even when not stimulated, which results in nervousness, muscle spasms and even convulsions and death

The three most important hormones for regulating renal reabsorption of Na+ and Cl-

Angiotensin II, aldosterone and atrial natriuretic peptide (ANP)

Bicarbonate

Bicarbonate ions are the second most common anion in extracellular fluids - Its primary function is as a buffer preventing large changes in pH (discussed shortly) - The concentration of bicarbonate present in arterial blood will be slightly lower than in venous blood This is because tissues will release CO2, which will combine with H2O forming carbonic acid, which dissociates into H+ and HCO3- The reaction reverses in the pulmonary capillaries, lowering concentrations as venous blood becomes arterial blood again - The kidneys are the main regulators of bicarbonate Intercalated cells of the kidneys can produce HCO3- and release it into the blood when levels are low Intercalated cells can also excrete excess HCO3- into the urine when blood levels are too high

Buffer systems

Buffer systems consist of a weak acid and the salt of the weak acid They stabilize pH by converting strong acids and bases into weak acids and bases Strong acids (and bases)rapidly and completely dissociate in water, releasing lots of H+ (or OH-); weak acids and bases do not completely dissociate, releasing far fewer H+ and OH- respectively

Calcium

Calcium is the most abundant mineral in the body However, 98% of it is stored in the bone and teeth Levels in body fluids are typically low - Beyond hardening teeth, functions in blood clotting, neurotransmitter release, maintaining muscle tone and the excitability of nervous and muscle tissue

Carbonic acid bicarbonate buffer

Carbonic acid-bicarbonate buffer system is based on the bicarbonate ion, HCO3- When pH drops (too much H+), the HCO3- functions as a weak base, removing the excess H+ H+ + HCO3- => H2CO3 Then in the lungs, carbonic acid dissociates into water and carbon dioxide, and the carbon dioxide is exhaled When pH increases (too little H+), carbonic acid functions as a weak acid, releasing H+ ions H2CO3 => H+ + HCO3- Because CO2 and H2O form carbonic acid, this buffer system cannot protect against pH changes from respiratory problems

Chloride

Chloride ions are the most prevalent anions in the extracellular fluid They can also easily move between the extracellular and intracellular fluid compartments via leak channels Because they can move between compartments, their primary function is balancing the level of anions in different fluid compartments One example is the chloride shift that occurs between RBCs and blood plasma as CO2 levels change - Chloride ions are also part of the hydrochloric acid secreted into gastric juice during digestion - Antidiuretic hormone helps to regulate Cl- balance in the body by regulating fluid loss - Processes that regulate renal Na+ reabsorption also regulate Cl- reabsorption They are moved by a Na+ / Cl- symporter

Kidney of excretion H+ (part 2)

Dumping all those H+ protons into the urine can make it really acidic Acidity can be elevated 1000 times (3 pH units) as compared to the blood That low pH could be problematic for the urinary system, so urine is buffered - The most plentiful buffer in tubular fluid is monohydrogen phosphate, HPO42- HPO42- will combine with H+, forming dihydrogen phosphate (H2PO4-) - In addition, a small amount of ammonia (NH3) will also be present NH3 will combine the H+, forming the ammonium ion, NH4+ - Both ammonium ions and dihydrogen phosphate cannot diffuse back into tubule cells, so they will be excreted in the urine while buffering the pH

Movement of water between body fluid compartments (part 3)

Excessive sweating, vomiting, blood loss and diarrhea can lead to extensive loss of water and Na+ If the water and Na+ are replaced with plain water, body fluids can become too dilute (lowered osmolarity) This too will result in water flowing into cells, causing them to swell The swelling of cells can lead to convulsions, coma and even death To prevent this outcome, solutions given to rehydrate a dehydrated person should include salts in the formulation

Magnesium function

Functionally, Mg2+ is a cofactor for numerous enzymes used in protein and carbohydrate metabolism Is also essential for neuromuscular activity, synaptic transmission and myocardial functioning Parathyroid secretion is also dependent on Mg2+ The kidneys increase urinary excretion of Mg2+ in response to hypercalcemia, hypomagnesemia, increases in extracellular fluid volume, decreases in parathyroid hormone and acidosis The opposite conditions will cause decrease in renal excretion

Hemoglobin (buffer for RBCs)

Hemoglobin is a very important pH buffer in the RBCs CO2 from tissues enters RBCs, reacting with H2O to form carbonic acid, H2CO3 Carbonic acid disassociates, releasing H+ and bicarbonate ion, HCO3- The H+ then binds to deoxyhemoglobin

acid base balance (part 2)

In a healthy person, arterial blood is maintained at a pH of 7.35-7.45 - Metabolic reactions typically produce large amounts of acids, which will lower the pH quickly to lethal levels To prevent this, the body has three mechanisms that will keep the pH of the body in normal limits - Buffer systems are fast acting systems that function to bind excess H+ from solution This raises the pH, but does not eliminate the excess H+ from the body - Exhalation of carbon dioxide reduces the level of CO2 from the blood This raises the pH of the blood by removing acid from the body - Excretion of H+ by the kidneys is the slowest method of removing H+ from the body However, it is the only way to remove acids other than carbonic acid from the body

Magnesium

In adults, 54% of magnesium is part of the bone matrix 45% is found in intracellular fluid and 1% is in the extracellular fluid This makes magnesium the 2nd most common cation in the intracellular fluid

Fluid compartment

In lean adults, body fluids compose 55% (female) and 60%(male) of the total body mass

Acid base balance

Ions are important in maintaining homeostasis One of the biggest challenges for the body is maintaining the H+ concentrations (pH) of body fluids This is absolutely critical, because most reactions in the body are catalyzed by enzymes Enzymes are proteins that require a specific 3 dimensional structure to function, and that 3D structure changes as pH changes

The major hormone that regulates water loss is antidiuretic hormone (ADH) (also called vasopressin)

Is produced by neurosecretory cells that extend from the hypothalamus to the posterior pituitary in response to increased osmolarity of body fluids (just like what occurs with the thirst mechanism) - ADH production causes the insertion of aquaporin 2 proteins into the apical surface of renal tubule cells This increases their water permeability, allowing them to reabsorb more water from the filtrate The recovered water will then move into the bloodstream - The reabsorbed water and intake of fluids from the thirst mechanism will decrease the osmolarity of the body fluids, ending ADH secretion Aquaporin 2 production stops and pores in the apical surface are quickly removed by endocytosis This lowers the permeability and increases water loss in the urine

Metabolic acidosis

Metabolic acidosis is marked by a drop in HCO3- in the arterial blood This causes blood pH to decrease, and is caused by three conditions Loss of HCO3- by severe diarrhea or renal dysfunction Accumulation of other acids in the blood Failure of the kidneys to excrete H+ from metabolism of dietary proteins If the problem is not too severe, hyperventilation can help bring the pH back to normal Treatment of metabolic acidosis consists of administering sodium bicarbonate and correcting the cause of the acidosis

Metabolic alkalosis

Metabolic alkalosis is marked by an increase in HCO3- in the arterial blood, raising the pH Non-respiratory loss of acids or excessive intake of alkaline drugs can induce it Excessive vomiting (most common cause), use of diuretics, endocrine disorders, excessive use of antacids and severe dehydration Respiratory compensation through hypoventilation may bring blood pH back to normal levels Treatments include giving fluids to correct electrolyte imbalances and correcting the cause of the alkalosis

Kidney excretion of H+

Metabolic processes produce tremendous quantities of non-volatile acids, such as sulfuric acid The only wat to remove this huge acid load is by secretion of H+ in the urine If this does not occur, death can quickly ensue - As we covered in the kidney lectures, both the proximal convoluted tubules and collecting ducts excrete H+ into the tubular fluid In the PCT, Na+/H+ antiporters secrete H+ while absorbing Na+ - However, the intercalated cells of the collecting tubes are more important for regulating body fluid pH The apical membrane of intercalated cells contain proton pumps These will excrete protons into the tubule fluid regardless of concentration gradient The H+ is generated from carbonic acid, which forms from CO2 and H2O The HCO3- produced from the carbonic acid is then transported across the basolateral surface by Cl- / HCO3- antiporters, where it enters the blood In the blood, the new bicarbonate ions can then buffer the non-volatile acids

Movement of water between body fluid compartments (part 2)

Minor changes in interstitial fluid osmolarity are not a big deal, but prolonged large changes are When a person consumes a large amount of water, osmolarity of interstitial fluid will decrease Normally the kidneys respond with producing large amounts of dilute urine However, if they continue to drink large quantities, they can overwhelm the kidneys, and cause water intoxication This results in major changes in interstitial fluid osmolarity, causing tissue cells to swell dangerously,

Electrolytes (fluid balance)

Most of the solutes in the body are electrolytes, inorganic compounds that dissociate into ions - Most water moves between intracellular and interstitial fluid by osmosis, making electrolyte concentrations critical for maintaining fluid balance - Most of the time water intake and electrolytes are not ingested in the same proportions that exist in the body - This makes the functions of the kidneys very important to maintaining homeostasis

Extracellular fluid differs considerably from intracellular fluid

Na+ and Cl- are the most abundant cation and anion in extracellular fluid, whereas K+ is the most abundant cation and proteins and phosphates are the most abundant anions in intracellular fluids This is accomplished by Na+/K+ pumps actively pumping Na+ into the interstitial fluid and K+ into the cytosol The high concentrations of protein and phosphate anions found in intracellular fluid is maintained because these are large molecules that are impermeable to the cellular membrane

Sodium regulation

Na+ levels in the blood are regulated by aldosterone, antidiuretic hormone (ADH) and atrial natriuretic peptide (ANP) Aldosterone increases renal reabsorption of Na+ When Na+ levels in the blood fall below 135mEq/l, hyponatremia is occurring In response, ADH production will be blocked, allowing more water to be excreted in urine This will elevate the concentration of Na+ in the extracellular fluid When Na+ levels are too high, hypernatremia is occurring In response, ANP will increase Na+ excretion by the kidneys, lowering the levels in the extracellular fluid

Movement of water between body fluid compartments

Normally cells exist in an isotonic environment, where the same concentration of solutes are found inside and outside of the cell Changes in the interstitial fluid can will change the fluid state inside the cells Increasing the osmolarity of the interstitial fluid causes fluid to be drawn out of cells, and they shrink, whereas decreasing the osmolarity of the interstitial fluid causes fluid to flow into cells, causing them to swell

Potassium

Potassium ions are the most abundant ions in intracellular fluid - Play a key role in establishing the resting membrane potential and repolarizing electrically excitable cells - Also helps maintain pH of body fluids When K+ moves into or out of a cell, it is often replaced with H+ - Normal levels of K+ in the blood plasma is controlled by aldosterone When blood levels of potassium are too high (hyperkalemia), more aldosterone will be secreted This will result in principal cells secreting more potassium into the urine When blood levels of potassium are too low (hypokalemia), less aldosterone will be secreted This will reduce potassium loss in the urine - Because K+ is needed for the repolarization phase of action potentials, abnormal concentrations can be lethal

Respiratory alkalosis

Respiratory alkalosis is marked by abnormally low PCO2 levels in arterial blood The cause of the drop in PCO2 is hyperventilation Can be caused by high altitude, pulmonary disease, stroke or extreme anxiety The kidneys will help to compensate by decreasing H+ secretion and HCO3- reabsorption Treatment of respiratory alkalosis is aimed at increasing the CO2 levels in the body A simple treatment is having the patient breath into a paper bag for a short period, so they inhale air with higher levels of CO2

Body water gain (cont.)

The amount of metabolic water formed in the body is dependent on the level of aerobic respiration occurring More ATP demand leads to more water, and vice versa Body water gain is mainly regulated by the volume of fluid intake (i.e. how much you drink each day) The thirst center, located in the hypothalamus, governs the urge to drink

Respiratory acidosis

The hallmark of respiratory acidosis is abnormally high PCO2 in arterial blood Inadequate exhalation of CO2 results in the buildup of H2CO3, and a lowering of blood pH Any condition that effects movement of CO2 from the blood can cause this, including emphysema, pulmonary edema, damage to the respiratory center of the medulla and airway obstruction If the respiratory problem isn't too severe, the kidneys will help compensate by increasing H+ secretion and HCO3- reabsorption The goal of treating respiratory acidosis is increasing exhalation of CO2 Providing ventilation therapy is common; intravenous administration of HCO3- may also be helpful

Exhalation of carbon dioxide

The level of carbon dioxide in the body fluids can also influence the pH of the fluid CO2 + H2O H2CO3 H+ + HCO3- When more CO2 is present, the reaction is driven to the right, and acidity increases When less CO2 is present, the reaction is driven to the left, and acidity decreases Because CO2 is removed by exhalation, the rate at which you exhale will effect the pH of the blood Doubling the respiratory rate will increase blood pH from 7.4 to 7.63 Reducing respiratory rate by half will lower the blood pH from 7.4 to 7.2

Calcium regulation

The most important regulator of Ca is parathyroid hormone (PTH) Low levels of Ca in the blood plasma promote PTH secretion PTH stimulates osteoclasts to release Ca from bone tissue Also enhances reabsorption of Ca from glomerular filtrate and increases calcitriol, to increase absorption of Ca from the diet Calcitonin, produced by the thyroid gland, inhibits the activity of osteoclasts, increases Ca deposition into bones, lowering blood Ca levels

Acidosis

The normal range of blood pH is 7.35-7.45 Acidosis is a condition where blood pH drops below 7.35 This can result in depression of the CNS; if pH falls below 7.0, patients often become disorientated, comatose, and may die Patients with severe acidosis often die while in a coma

Extracellular fluid

The other 1/3 is extracellular fluid - 80% is the interstitial fluid that bathes cells and occupies the spaces between tissue cells Included in this is the lymph, cerebrospinal fluid, synovial fluid, aqueous humor and vitreous body of the eyes, endolymph and perilymph in the ears and the serous fluid - 20% is the plasma, the fluid portion of the blood

Phosphate buffer

The phosphate buffer system functions in a similar fashion to the carbonic acid - bicarbonate system - It utilizes dihydrogen phosphate (H2PO4-) and monohydrogen phosphate (HPO42-) - Production of strong bases cause pH to rise (excess OH-) In response, dihydrogen phosphate will bind to the OH-, creating water and monohydrogen phosphate OH- + H2PO4- => H2O + HPO42- - Production of strong acids cause pH to decrease (excess H+) In response, monohydrogen phosphate will bind to the excess hydrogen, creating dihydrogen phosphate H+ + HPO42- => H2PO4- - Because phosphates are found in high concentrations in intracellular fluid, it is an important regulator of cytosolic pH

Using the mEq method, we can compare the electrolyte concentrations in body fluids (btwn. interstitial, extracellular and blood plasma)

The primary difference between blood plasma and interstitial fluid, the two extracellular fluids, is blood plasma has protein anions present, where interstitial fluid does not This is a product of the capillaries being essentially impervious to proteins, preventing them from reaching the interstitial fluid Otherwise, they are highly similar

Protein buffer

The protein buffer system is the most abundant buffer in intracellular fluid and blood plasma Proteins contain both an amine group and a carboxyl group When pH rises (becomes more basic), there is a shortage of H+ The carboxyl group (COOH) will release its hydrogen as H+, lowering the pH of the fluid When the pH lowers (becomes more acidic), there are too many H+ The amine group (NH2) will bind excess H+ ions, becoming NH3+, raising the pH

Electrolytes in body fluids

To compare the charge carried by ions in different solutions, the concentration of ions is typically expressed in milliequivalents per liter (mEq/l) One equivalent is the positive or negative charge equal to the charge of one mole of H+, so one mEq will be one-thousandth of an equivalent For ions with a single charge (like Na+ or K+), the mEq/l is equal to the mmol/l concentration For ions with two charges (Ca2+ or Mg2+), the mEq/l will be twice the mmol/l

Water (fluid balance)

Water is the largest single component of the body, constituting 45-75% of the total body mass The water composing the bodies compartments is constantly being exchanged through filtration, reabsorption diffusion and osmosis Yet the relative volume in each compartment is typically very stable

Angiotensin II and aldosterone

When dehydrated, angiotensin II stimulates secretion of aldosterone Aldosterone promotes reabsorption of Na+ and Cl- by the kidneys This in turn increases water reabsorption (water follows the solutes), conserving blood volume - Increased blood volume also slows renin release from juxtaglomerular cells Less renin means less angiotensin II is produced Lower angiotensin levels will increase glomerular filtration and lower water, Na+ and Cl- absorption Less angiotensin II also means less aldosterone Less aldosterone also inhibits Na+ and Cl- reabsorption

Fluid balance

When the proper amounts of water and solutes are present and correctly proportioned among the various compartments of the body, it is said to be in fluid balance

Dehydration

When water loss is greater than water gain, dehydration, a decrease in volume and increase in osmolality of body fluids, occurs - Dehydration is detected and transmitted to the thirst center three ways - Neurons in the mouth will detect dryness from decreases saliva production - Baroreceptors will detect lowered blood pressure in the heart and blood vessels - Decreases in blood volume result in lowered blood pressure and increased blood osmolality The lowered blood pressure will stimulates the kidneys to release renin, which promotes angiotensin II formation The increased blood osmolality and angiotensin II production will increase nerve impulses from osmoreceptors in the hypothalamus to the thirst centers

pH (acid base balance

pH is expresses on a log scale, where 7 is neutral At this pH, the amount of H+ in solution is equal to the amount of OH- If one moves from pH 7 to pH 6, you have a tenfold increase in the number of H+ ions present in the solution If you move from pH 7 to pH 8, you have a tenfold reduction in the number of H+ ions present

Exhalation of carbon dioxide (part 2)

pH of body fluids and respiratory rate interact via a negative feedback loop A decrease in pH of the blood will be detected by central chemoreceptors in the medulla oblongata and peripheral chemoreceptors in the aortic and carotid bodies They will respond by stimulating the dorsal respiratory group in the medulla oblongata The DRG will stimulate the diaphragm and other respiratory muscles to contract more forcefully This will increase the amount of CO2 exhaled, reducing H2CO3 levels in the body fluids, increasing pH Because carbonic acid can be eliminated via respiration, it is called a volatile acid