PATHOPHYSIOLOGY Name
Chapter 4: Fluids and Electrolytes, Acids and Bases
I. Fluid and Electrolyte Balance A. Distribution of Body Fluids 1. Total body water (TBW) - 60% of body weight, on average, for a normal adult male. a. Fluid compartments Intracellular fluid (2/3 of total body water or about 28 L) Extracellular fluid (1/3 of total body water or about 14L) o Interstitial fluid (about 11L) o Intravascular fluid (about 3L) o Lymph, synovial, intestinal, CSF, sweat, urine, pleural, peritoneal, pericardial, and intraocular fluids (less than 1L) b. Pediatrics 75% to 80% of body weight Susceptible to significant changes in body fluids o Dehydration c. Aging The percentage of total body weight that is fluid decreases. o Increase adipose and decrease muscle mass o Renal decline o Diminished thirst perception 2. Water Movement Between the Intravascular and Interstitial Spaces Net filtration = forces favoring filtration minus forces opposing filtration (Starling’s hypothesis) o Forces favoring filtration into interstitial spaces . Capillary hydrostatic pressure (blood pressure) . Interstitial oncotic pressure (water-pulling) o Forces favoring reabsorption into blood . Plasma oncotic pressure (water-pulling) . Interstitial hydrostatic pressure (pushes into blood and cells) 3. Water Movement Between the Intracellular (ICF) and Extracellular (ECF) Fluid Compartments Caused by changes in the concentration of ECF (osmotic pressure differences). If ECF becomes less concentrated (due to fluid excess or sodium deficit) water flows into cells and they swell. If ECF becomes more concentrated (due to fluid deficit or sodium excess) water flows out of cells and they shrink. 2
ACTIVITY 1: For each of the following statements, decide which direction fluid would tend to move. Choices: B = into the blood I = into the interstitial fluid C = into the cells Lower than normal sodium levels. Low blood pressure. Higher than normal sodium levels. Lower than normal levels of plasma proteins. High blood pressure. Higher than normal levels of plasma proteins.
B. Alterations in Water Movement 1. Edema Accumulation of fluid within the interstitial spaces Causes o Increase in capillary hydrostatic pressure o Decrease in plasma oncotic pressure o Increases in capillary permeability o Lymph obstruction 2. Water Balance Thirst perception Antidiuretic hormone (ADH) secretion o ADH causes increased water reabsorption. o Occurs when plasma volume drops or plasma concentration (osmolality) increases. Osmolality receptors sense increased osmolality and plasma volume depletion. C. Sodium and Chloride Balance 1. Sodium Primary ECF cation Regulates osmotic forces Roles - neuromuscular irritability, acid-base balance, and cellular chemical reactions and membrane transport 2. Chloride Primary ECF anion Provides electroneutrality Levels vary inversely with those of bicarbonate 3. Sodium and Chloride Regulation Renin-angiotensin-aldosterone (RAA) system: Trigger: A decrease in blood pressure and blood flow to the kidneys (or increased K+). Step 1: Renin is released by juxtaglomerular cells of the kidney. Step 2: Renin is an enzyme that converts angiotensinogen to angiotensin I (in the blood). 3
Step 3: Angiotensin I is converted to angiotensin II (occurs in the lungs; requires angiotensin converting enzyme [ACE]). Step 4: Angiotensin II causes vasoconstriction and release of aldosterone by the adrenal cortex. Step 5: Aldosterone causes increased sodium and water retention in the kidneys. End result: An increase in blood volume and blood pressure. Atrial natriuretic hormone (peptide) (ANH) – has the opposite effect of aldosterone o ANH is secreted by the atria in response to increased blood volume (stretching). o Function: ANH decreases sodium retention so more sodium and water are excreted in the urine. This decreases blood volume and blood pressure.
ACTIVITY 2: Match the hormones with their descriptions. a. ADH b. aldosterone c. atrial natriuretic hormone Causes increased retention of sodium and water when blood pressure falls. Causes more water to be reabsorbed when the plasma becomes too concentrated. Causes excretion of sodium and water when blood volume becomes too great.
D. Alterations in Sodium, Chloride and Water Balance 1. Isotonic Alterations Isotonic fluid has the same water-to-electrolyte content as normal body fluid. Total body water change with proportional electrolyte and water change. a. Isotonic fluid loss (isotonic dehydration) o Causes - hemorrhage, mild vomiting, mild diarrhea or excessive sweating. o Manifestations - weight loss, dryness of skin and mucous membranes, decreased skin turgor, decreased urine output, and symptoms of hypovolemia (rapid heart rate, flattened neck veins, and normal or decreased blood pressure, and shock). b. Isotonic fluid excess o Causes – excessive administration of intravenous fluids, hypersecretion of aldosterone, or drugs such as cortisone. o Manifestations – symptoms of hypervolemia including weight gain, decreased hematocrit, distended neck veins, increase in BP, and edema. 2. Hypertonic Alterations o Increased osmolality (fluid is more concentrated) a. Hypernatremia o Serum sodium >147 mEq/L o Water moves from the ICF to the ECF, causing intracellular dehydration including shrinkage of brain cells; but there is excess extracellular fluid. o Causes - excess administration of hypertonic IV solutions, oversecretion of aldosterone. 4
o Manifestations of hypernatremia . Increased ECF causes edema and increased blood pressure. . High sodium level causes muscular weakness and hyperactive reflexes. . Decreased ICF causes thirst, decreased urine output, confusion, and ultimately coma. b. Pure water deficit (hypertonic dehydration) o Loss of water alone . ECF becomes more concentrated, so water moves from ICF to ECF. . Both ECF and ICF become dehydrated and hypovolemia occurs. o Causes . Inability to obtain water (ex. comatose patients) . Extended hyperventilation . Increased renal free water clearance as with decreased ADH secretion (most common cause) o Manifestations . Decreased ECF causes a weak pulse, postural hypotension, and tachycardia, elevated hematocrit and elevated serum sodium level. . Decreased ICF causes thirst, fever, decreased urine output, shrinkage of brain cells, confusion and coma. 3. Hypotonic Alterations o Decreased osmolality (fluid is less concentrated) a. Hyponatremia o Serum sodium level <135 mEq/L o Sodium deficit decreases the ECF osmotic pressure, and water moves into the cells. . Water movement causes symptoms related to hypovolemia and cellular swelling. o Causes – inadequate intake of Na+; hypoaldosteronism; increased loss of Na+ through diuresis, profuse sweating, or gastrointestinal losses. o Manifestations – Increased ICF causes edema, brain cell swelling, irritability, depression, confusion, weakness, muscle cramps, anorexia, nausea, and diarrhea. . Pure sodium deficits cause hypotension, tachycardia, and decreased urine output. b. Water excess o Free water excess causes symptoms of hypervolemia and water intoxication. o Causes – excessive administration of hypotonic intravenous solutions, drinking water to replace isotonic fluid losses, tap water enemas, psychogenic polydipsia, renal water retention, or increased antidiuretic hormone secretion. o Manifestations . Acute excesses cause swelling of brain cells, confusion and convulsions. . Long-term water accumulation causes weakness, nausea, muscle twitching, headache, and weight gain. 5 ACTIVITY 3: Place an X in the appropriate squares to indicate which fluid imbalances (on left) are accompanied by the conditions listed in the top row (there should be a total of ten Xs).
Hypovolemia Hypervolemia Cells shrink Cells swell Isotonic fluid loss Isotonic fluid excess Hypernatremia Pure water deficit Hyponatremia Water excess
E. Alterations in Potassium 1. Potassium Major intracellular cation Concentration maintained by 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. Serum levels of K+ are regulated by kidney excretion of potassium. Potassium Levels Changes in pH affect K+ balance o Hydrogen ions accumulate in the ICF during states of acidosis. K+ shifts out of cells to maintain a balance of cations across the membrane. Aldosterone and insulin influence serum potassium levels. o Aldosterone – is secreted in response to high K+ levels; causes increased movement of K+ into urine in exchange for Na+. o Insulin – stimulates cellular uptake of K+. 2. Hypokalemia Potassium level <3.5 mEq/L Potassium balance is described by changes in plasma potassium levels Causes – reduced intake of potassium, increased entry of potassium into body cells (as during alkalosis), and increased loss of potassium in diarrhea or due to diuresis from the kidneys. Loop diuretics (like Lasix) - inhibit Na+ reabsorption in the loop of Henle, and so put an excess demand on the exchange of K+ for Na+ in the distal tubule of the nephron, thus resulting in K+ loss. Manifestations o Membrane hyperpolarization causes a decrease in neuromuscular excitability, skeletal muscle weakness, smooth muscle atony, and cardiac dysrhythmias. 6
3. Hyperkalemia Potassium level >5.5 mEq/L Hyperkalemia is rare because of efficient renal excretion Caused by increased intake, shift of K+ from ICF (as during acidosis), decreased renal excretion due to renal failure, insulin deficiency, or cell trauma Mild attacks o Increased neuromuscular irritability o Tingling of lips and fingers, restlessness, intestinal cramping, and diarrhea Severe attacks o The cell is not able to repolarize, resulting in muscle weakness, loss of muscle tone, flaccid paralysis, and even cardiac arrest.
ACTIVITY 4: Indicate whether each of the following is associated with hypokalemia (-) or hyperkalemia (+). Acidosis. Use of loop diuretics. Renal failure. Alkalosis. Trauma to cells. Increased neuromuscular. Excess aldosterone. Injection of insulin. irritability.
II. Acid Base Balance A. Hydrogen Ion and pH 1. pH pH = Inverse logarithm of the H+ concentration If the H+ are high in number, the pH is low (acidic). If the H+ are low in number, the pH is high (alkaline). The pH scale ranges from 0 to 14: 0 is very acidic, 14 is very alkaline. Each number represents a factor of 10. If a solution moves from a pH of 6 to a pH of 5, the H+ have increased 10 times. 2. Acids Acids are formed as end products of protein, carbohydrate, and fat metabolism To maintain the body’s normal pH (7.35-7.45) the H+ must be neutralized or excreted The bones, lungs, and kidneys are the major organs involved in the regulation of acid and base balance Body acids exist in two forms
o Volatile acid - CO2
CO2 reacts with water to produce carbonic acid (H2CO3), which partially dissociates + - to form H and HCO3 . - + CO2 + H2O H2CO3 HCO3 + H 7
- . HCO3 (bicarbonate ion) is the major pH buffer in body fluids.
. CO2 is a volatile acid because it can be blown off by the lungs. o Nonvolatile acids . Sulfuric, phosphoric, and other organic acids – . Eliminated by the renal tubules with the regulation of HCO3 B. Buffer 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 1. 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 o At a pH of 7.4, the ratio of bicarbonate to carbonic acid is 20:1 o Bicarbonate and carbonic acid can increase or decrease, but the ratio must be maintained If the 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 referred to as compensation o The respiratory system compensates by increasing or decreasing ventilation o The renal system compensates by producing acidic or alkaline urine 2. Other Buffering Systems a. Protein buffering o Proteins like albumin have negative charges, so they can serve as buffers for H+ b. Renal buffering + – o Secretion of H in the urine and reabsorption of HCO3 c. Cellular ion exchange o Exchange of K+ for H+ in acidosis and alkalosis C. Acid-Base Imbalances 1. Respiratory Imbalances
When either too much or too little CO2 is cleared from the blood as it passes through pulmonary capillaries, acid/base imbalances occur. a. Respiratory Acidosis
o Hypoventilation results in an excess of CO2 remaining in the blood, which in turn produces an excess of carbonic acid. o This commonly occurs in diseases such as chronic bronchitis and acute respiratory distress syndrome. 8
b. Respiratory Alkalosis
o Hyperventilation results in a deficiency of CO2, which in turn produces a deficiency of carbonic acid. This causes a decreased amount of H+ in the blood, so the pH becomes more alkaline. o Hyperventilation occurs in anxiety attacks (also called hyperventilation syndrome), at high altitudes in normal people, and in some individuals with emphysema. 2. Metabolic Imbalances a. Metabolic Acidosis o Occurs when production of metabolic acids causes a reduced bicarbonate concentration, because bicarbonate ion is used up buffering the metabolic acids. Since there is less of the basic bicarbonate ion, body fluids are more acidic. o Can be caused by ketoacids produced from fat breakdown in diabetes (particularly IDDM), poisons (e.g. aspirin), waste products that accumulate during renal failure, and lactic acid produced by anaerobic exercise. o Non-volatile acids must be metabolized, usually by the liver, or removed by the kidneys. o Hydrogen ion (H+) and potassium ion (K+) are secreted in the distal convoluted tubule of the nephron in exchange for sodium ion (Na+). o H+ and K+ tend to go up and down together, so an increase in K+ usually implies metabolic acidosis, while a decrease in K+ usually implies metabolic alkalosis. b. Metabolic Alkalosis o While probably less common than metabolic acidosis, metabolic alkalosis does occur. o Common causes include vomiting, which eliminates significant quantities of stomach acids, and ingestion or infusion of bicarbonate. For example, excessive use of antacids may result in metabolic alkalosis. o Loop diuretics (like Lasix) – recall that these inhibit Na+ reabsorption in the loop of Henle, and so put an excess demand on reabsorption of Na+ in the distal tubule of the nephron. In this region Na+ can be exchanged for either K+ or H+, so the H+ level in the blood goes down. o Metabolic alkalosis and acidosis are usually accompanied by a variety of homeostatic problems, and can thus be very difficult to understand.
ACTIVITY 5: Indicate whether each of the following would make the blood more acidic (A) or more basic (B). + More CO2 in blood. More H shifts to urine. Hyperventilation. – More HCO3 in blood. Eating antacids. Hypoventilation. More K+ moves into cells. Excess lactic acid production. Loop diuretics. 9
D. So How Do I Tell?
Measurements of blood gases are important in identifying pH imbalances. 1. Uncompensated Respiratory Acidosis
Characterized by elevated PCO2 and reduced pH. Bicarbonate is relatively normal. Compensation - If the respiratory acidosis continues over an extended time, the kidneys will compensate by retaining bicarbonate.
In this case the bicarbonate concentration will be above normal, PCO2 will be above normal, and pH will be closer to normal, but still low. 2. Uncompensated Respiratory Alkalosis
Characterized by low PCO2, elevated pH, and relatively normal bicarbonate. Compensation - Over time, the kidneys will compensate by excreting more bicarbonate.
In this case PCO2 is still low, bicarbonate will be low as well, and pH will be returned toward, but not to, normal. 3. Uncompensated Metabolic Acidosis Characterized by low pH, and reduced bicarbonate.
Compensation - The respiratory system compensates by blowing off CO2, thus increasing pH toward normal. Because metabolic acidosis usually develops slowly, respiratory compensation usually occurs as fast as the acidosis develops, so the compensation may not be easy to detect. 4. Uncompensated Metabolic Alkalosis Characterized by elevated pH and elevated bicarbonate. Compensation - Respiratory compensation is accomplished by hypoventilation, resulting in
the retention of CO2 and the lowering of pH toward normal. 5. pH Imbalance Summary
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6. Combined pH Imbalance Problems
Unfortunately, metabolic and respiratory problems often occur together, resulting in a combined respiratory/metabolic pH imbalance. For example, a myocardial infarction produces metabolic acidosis from poor perfusion, and the anxiety resulting from the pain causes hyperventilation and respiratory alkalosis. In addition to supporting the function of the heart, the clinical challenge is to treat both of these at once, and achieve homeostasis.
ACID-BASE PRACTICE: Identify the type of imbalance occurring for each set of values below: - pH Pco2 HCO3 Imbalance Occurring: 7.31 50 24 7.50 32 24 7.30 32 15 7.36 70 38 7.77 35 50 7.44 44 29 7.34 40 17
E. 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 + HCO3 + 10 to 12 mEq/L (other miscellaneous anions [the ones we don’t measure]—phosphates, sulfates, organic acids, etc.) An abnormal anion gap occurs as a result of an increased level of an abnormal unmeasured anion. Examples: diabetic ketoacids, salicylate poisoning, lactic acidosis, renal failure, etc. As these abnormal anions accumulate, the measured anions have to decrease to maintain electroneutrality
11 ANSWER KEY TO ACTIVITIES
ACTIVITY 1: For each of the following statements, decide which direction fluid would tend to move. Choices: B = into the blood I = into the interstitial fluid C = into the cells C Lower than normal sodium levels. B Low blood pressure. I Higher than normal sodium levels. I Lower than normal levels of plasma proteins. I High blood pressure. B Higher than normal levels of plasma proteins.
ACTIVITY 2: Match the hormones with their descriptions. a. ADH b. aldosterone c. atrial natriuretic hormone B Causes increased retention of sodium and water when blood pressure falls. A Causes more water to be reabsorbed when the plasma becomes too concentrated. C Causes excretion of sodium and water when blood volume becomes too great.
ACTIVITY 3: Place an X in the appropriate squares to indicate which fluid imbalances (on left) are accompanied by the conditions listed in the top row (there should be a total of ten Xs).
Hypovolemia Hypervolemia Cells shrink Cells swell Isotonic fluid loss X Isotonic fluid excess X Hypernatremia X X Pure water deficit X X Hyponatremia X X Water excess X X
ACTIVITY 4: Indicate whether each of the following is associated with hypokalemia (-) or hyperkalemia (+). + Acidosis. - Use of loop diuretics. + Renal failure. - Alkalosis. + Trauma to cells. + Increased neuromuscular - Excess aldosterone. - Injection of insulin. irritability. o
ACTIVITY 5: Indicate whether each of the following would make the blood more acidic (A) or more basic (B). + A More CO2 in blood. B More H shifts to urine. B Hyperventilation. – B More HCO3 in blood. B Eating antacids. A Hypoventilation. A More K+ moves into cells. A Excess lactic acid production. B Loop diuretics.
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ACID-BASE PRACTICE: Identify the type of imbalance occurring for each set of values below:
- pH Pco2 HCO3 Imbalance Occurring: 7.31 50 24 Uncompensated respiratory acidosis 7.50 32 24 Uncompensated respiratory alkalosis 7.30 32 15 Compensated metabolic acidosis 7.36 70 38 Compensated respiratory acidosis 7.77 35 50 Combined alkalosis 7.44 44 29 Compensated metabolic alkalosis 7.34 40 17 Uncompensated metabolic acidosis