The Cellular Environment: Fluids and Electrolytes, Acids and Bases Chapter 3 Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.

2 Distribution of Body Fluids  Total body water (TBW)  Intracellular fluid  Extracellular fluid Interstitial fluid Interstitial fluid Intravascular fluid Intravascular fluid Lymph, synovial, intestinal, biliary, hepatic, pancreatic, CSF, sweat, urine, pleural, peritoneal, pericardial, and intraocular fluids Lymph, synovial, intestinal, biliary, hepatic, pancreatic, CSF, sweat, urine, pleural, peritoneal, pericardial, and intraocular fluids

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 3 Water Movement Between the ICF and ECF  Osmolality  Osmotic forces  Aquaporins  Starling hypothesis  Net filtration = forces favoring filtration – forces opposing filtration

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 4 Water Movement Between the ICF and ECF

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 5 Net Filtration  Forces favoring filtration  Capillary hydrostatic pressure (blood pressure)  Interstitial oncotic pressure (water-pulling)  Forces favoring reabsorption  Plasma oncotic pressure (water-pulling)  Interstitial hydrostatic pressure

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 6 Osmotic Equilibrium

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 7 Alterations in Water Movement: Edema  Accumulation of fluid within the interstitial spaces  Causes  Increase in capillary hydrostatic pressure  Losses or diminished production of plasma albumin  Increases in capillary permeability  Lymph obstruction (lymphedema)

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 8 Water Balance  Thirst perception  Osmolality receptors Hyperosmolality Hyperosmolality  Baroreceptors stimulated Plasma volume depletion Plasma volume depletion  ADH secretion

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 9 Na + and Cl – Balance  Sodium  Primary ECF cation  Regulates osmotic forces  Roles Neuromuscular irritability, acid-base balance, and cellular reactions Neuromuscular irritability, acid-base balance, and cellular reactions  Chloride  Primary ECF anion  Provides electroneutrality

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 10 Na + and Cl – Balance  Renin-angiotensin-aldosterone system  Aldosterone  Natriuretic peptides  Atrial natriuretic peptide  Brain natriuretic peptide  Urodilantin (kidney)

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 11 Alterations in Na +, Cl –, and Water Balance  Isotonic alterations  Total body water change with proportional electrolyte change  Isotonic volume depletion  Isotonic volume excess

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 12 Hypertonic Alterations  Hypernatremia  Serum sodium >147 mEq/L  Related to sodium gain or water loss  Water movement from the ICF to the ECF Intracellular dehydration Intracellular dehydration  Manifestations: intracellular dehydration, convulsions, pulmonary edema, hypotension, tachycardia

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 13 Hypertonic Alterations  Water deficit  Dehydration  Pure water deficits  Renal free water clearance  Manifestations Tachycardia, weak pulse, and postural hypotension Tachycardia, weak pulse, and postural hypotension Elevated hematocrit and serum sodium levels Elevated hematocrit and serum sodium levels

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 14 Hypertonic Alterations  Hyperchloremia  Occurs with hypernatremia or a bicarbonate deficit  Usually secondary to pathophysiologic processes  Managed by treating underlying disorders

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 15 Hypotonic Alterations  Decreased osmolality  Hyponatremia or free water excess  Hyponatremia decreases the ECF osmotic pressure, and water moves into the cell  Water movement causes symptoms related to hypovolemia

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 16 Hypotonic Alterations  Hyponatremia  Serum sodium level <135 mEq/L  Sodium deficits cause plasma hypoosmolality and cellular swelling Pure sodium deficits Pure sodium deficits Low intake Low intake Dilutional hyponatremia Dilutional hyponatremia Hypoosmolar hyponatremia Hypoosmolar hyponatremia Hypertonic hyponatremia Hypertonic hyponatremia

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 17 Hypotonic Alterations  Water excess  Compulsive water drinking  Decreased urine formation  Syndrome of inappropriate ADH (SIADH) ADH secretion in the absence of hypovolemia or hyperosmolality ADH secretion in the absence of hypovolemia or hyperosmolality Hyponatremia with hypervolemia Hyponatremia with hypervolemia  Manifestations: cerebral edema, muscle twitching, headache, and weight gain

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 18 Hypotonic Alterations  Hypochloremia  Usually the result of hyponatremia or elevated bicarbonate concentration  Develops due to vomiting and the loss of HCl  Occurs in cystic fibrosis

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 19 Potassium  Major intracellular cation  Concentration maintained by the Na +,K + pump  Regulates intracellular electrical neutrality in relation to Na + and H +  Essential for transmission and conduction of nerve impulses, normal cardiac rhythms, and skeletal and smooth muscle contraction

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 20 Potassium Levels  Changes in pH affect K + balance  Hydrogen ions accumulate in the ICF during states of acidosis. K + shifts out to maintain a balance of cations across the membrane.  Aldosterone, insulin, and catecholamines influence serum potassium levels

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 21 Hypokalemia  Potassium level <3.5 mEq/L  Potassium balance described by changes in plasma potassium levels  Causes: reduced potassium intake, increased potassium entry, and increased potassium loss  Manifestations  Membrane hyperpolarization causes a decrease in neuromuscular excitability, skeletal muscle weakness, smooth muscle atony, and cardiac dysrhythmias

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 22 Hyperkalemia  Potassium level >5.5 mEq/L  Hyperkalemia is rare due to efficient renal excretion  Caused by increased intake, shift of K + from ICF, decreased renal excretion, insulin deficiency, or cell trauma

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 23 Hyperkalemia  Mild attacks  Hypopolarized membrane, causing neuromuscular irritability Tingling of lips and fingers, restlessness, intestinal cramping, and diarrhea Tingling of lips and fingers, restlessness, intestinal cramping, and diarrhea  Severe attacks  The cell is unable to repolarize, resulting in muscle weakness, loss of muscle tone, flaccid paralysis, cardiac arrest

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 24 Calcium  Most calcium is located in the bone as hydroxyapatite  Necessary for structure of bones and teeth, blood clotting, hormone secretion, and cell receptor function

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 25 Phosphate  Like calcium, most phosphate (85%) is also located in the bone  Necessary for high-energy bonds located in creatine phosphate and ATP and acts as an anion buffer  Calcium and phosphate concentrations are rigidly controlled  Ca ++ x HPO 4 – – = K + (constant)  If concentration of one increases, that of the other decreases

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 26 Calcium and Phosphate  Regulated by three hormones  Parathyroid hormone (PTH) Increases plasma calcium levels via bone reabsorption Increases plasma calcium levels via bone reabsorption  Vitamin D Fat-soluble steroid; increases calcium absorption from the GI tract Fat-soluble steroid; increases calcium absorption from the GI tract  Calcitonin Decreases plasma calcium levels Decreases plasma calcium levels

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 27 Hypocalcemia and Hypercalcemia  Hypocalcemia  Decreases the block of Na + into the cell  Increased neuromuscular excitability (partial depolarization)  Muscle cramps  Hypercalcemia  Increases the block of Na + into the cell  Decreased neuromuscular excitability  Muscle weakness  Increased bone fractures  Kidney stones  Constipation

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 28 Hypophosphatemia and Hyperphosphatemia  Hypophosphatemia  Osteomalacia (soft bones)  Muscle weakness  Bleeding disorders (platelet impairment)  Anemia  Leukocyte alterations  Antacids bind phosphate  Hyperphosphatemia  See Hypocalcemia  High phosphate levels are related to the low calcium levels

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 29 Magnesium  Intracellular cation  Plasma concentration is 1.8 to 2.4 mEq/L  Acts as a co-factor in protein and nucleic acid synthesis reactions  Required for ATPase activity  Decreases acetylcholine release at the neuromuscular junction

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 30 Hypomagnesemia and Hypermagnesemia  Hypomagnesemia  Associated with hypocalcemia and hypokalemia  Neuromuscular irritability  Tetany  Convulsions  Hyperactive reflexes  Hypermagnesemia  Skeletal muscle depression  Muscle weakness  Hypotension  Respiratory depression  Lethargy, drowsiness  Bradycardia

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 31 pH: What Is It?  Negative logarithm of the H + concentration  Each number represents a factor of 10. If a solution moves from a pH of 7 to a pH of 6, the H + ions have increased 10-fold. Very acidic Very alkaline 014 Neutral 7 Increasing H+ pH scale Decreasing H+

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 32 pH  Inverse logarithm of the H + concentration  H + high in number, pH is low (acidic)  H + low in number, pH is high (alkaline)  Ranges from 0 to 14  Each number represents a factor of 10.  If a solution moves from a pH of 6 to a pH of 5, the H + has increased 10 times

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 33 pH  Acids are formed as end products of protein, carbohydrate, and fat metabolism  To maintain the body’s normal pH ( ) the H + must be neutralized or excreted  Bones, lungs, and kidneys are major organs involved in regulation of acid-base balance

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 34 pH  Body acids exist in two forms  Volatile H 2 CO 3 (can be eliminated as CO 2 gas) H 2 CO 3 (can be eliminated as CO 2 gas)  Nonvolatile Sulfuric, phosphoric, and other organic acids Sulfuric, phosphoric, and other organic acids Eliminated by the renal tubules with the regulation of HCO 3 – Eliminated by the renal tubules with the regulation of HCO 3 –

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 35 Buffering Systems  Buffer systems exist as buffer pairs  Associate and dissociate very quickly (instantaneous)  Buffer changes occur in response to changes in acid-base status

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 36 Buffering Systems  A buffer is a chemical that can bind excessive H + or OH – without a significant change in pH  A buffering pair consists of a weak acid and its conjugate base  The most important plasma buffering systems are the carbonic acid–bicarbonate system and hemoglobin

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 37 Carbonic Acid–Bicarbonate Pair  Operates in the lung and the kidney  The greater the partial pressure of carbon dioxide, the more carbonic acid is formed  At a pH of 7.4, the ratio of bicarbonate to carbonic acid is 20:1  Bicarbonate and carbonic acid can increase or decrease, but the ratio must be maintained

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 38 Carbonic Acid–Bicarbonate Pair  If amount of bicarbonate decreases, the pH decreases, causing a state of acidosis  The pH can be returned to normal if the amount of carbonic acid also decreases  This type of pH adjustment is called compensation  The respiratory system compensates by increasing or decreasing ventilation  The renal system compensates by producing acidic or alkaline urine

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 39 Other Buffering Systems  Protein buffering  Proteins have negative charges, so they can serve as buffers for H +  Renal buffering  Secretion of H + in the urine and reabsorption of HCO 3 –  Cellular ion exchange  Exchange of K + for H + in acidosis and alkalosis (alters serum potassium)

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 40 Acid-Base Imbalances  Normal arterial blood pH  7.35 to 7.45  Obtained by arterial blood gas (ABG) sampling  Acidosis  Systemic increase in H + concentration  Alkalosis  Systemic decrease in H + concentration

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 41 Acidosis and Alkalosis  Four categories of acid-base imbalances  Respiratory acidosis—elevation of p CO 2 due to ventilation depression  Respiratory alkalosis—depression of p CO 2 due to alveolar hyperventilation  Metabolic acidosis—depression of HCO 3 – or an increase in noncarbonic acids  Metabolic alkalosis—elevation of HCO 3 – usually due to an excessive loss of metabolic acids

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 42 Compensation  Renal  Alters bicarbonate and H + levels in response to acidosis or alkalosis Much slower response Much slower response Excretion and/or reabsorption Excretion and/or reabsorption  Respiratory  Alters CO 2 retention or loss in response to alkalosis or acidosis Rapid response Rapid response Respiratory rate alterations Respiratory rate alterations

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 43 Compensation  When adjustments are made to bicarbonate and carbonic acid in order to maintain the 20:1 ratio and therefore maintain normal pH  The actual values for bicarbonate to carbonic acid ratio are not normal but the normal ratio is achieved

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 44 Correction  Correction occurs when the values for BOTH components of the buffer pair (carbonic acid and bicarbonate) have also returned to normal levels

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 45 Metabolic Acidosis

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 46 Anion Gap  Used cautiously to distinguish different types of metabolic acidosis  By rule, the concentration of anions (–) should equal the concentration of cations (+). Not all normal anions are routinely measured.  Normal anion gap = Na + + K + = Cl – + HCO 3 – + 10 to 12 mEq/L (other misc. anions [the ones we don’t measure]—phosphates, sulfates, organic acids, etc.)

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 47 Anion Gap  Abnormal anion gap occurs due to an increased level of abnormal unmeasured anion  Examples: DKA—ketones, salicylate poisoning, lactic acidosis—increased lactic acid, renal failure, etc.  As these abnormal anions accumulate, the measured anions have to decrease to maintain electroneutrality

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 48 Metabolic Alkalosis

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 49 Respiratory Acidosis

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 50 Respiratory Alkalosis

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 51Summary