Fluid and Electrolytes Body Fluids Body Fluids Fluid Compartments

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Body Fluids

• Body water and dissolved substances – Cells need a stable environment to function Fluid and Electrolytes

• Body water content • Total body water ≈ 40 L – Infants • Where is it all?? • 73% or more water – 1. Intracellular fluid (ICF) compartment Adult males • 2/3 (25 L) • ~60% water 2. Extracellular fluid (ECF) compartment – Adult females • 1/3 (15 L) • ~50% water a. Plasma: 3 L – Higher fat content & less skeletal muscle mass b. Interstitial fluid (IF): 12 L – Water content declines with old age c. Other ECF • ~45% • Lymph, CSF, humors of the eye, synovial fluid, serous fluid, gastrointestinal secretions

Fluid Compartments Total body water Volume = 40 L 60% body weight Extracellular fluid (ECF) • Intracellular fluid Volume = 15 L 20% body weight – Metabolic reactions – Homeostasis essential to health

Intracellular fluid (ICF) Interstitial fluid (IF) Volume = 25 L Volume = 12 L 40% body weight 80% of ECF

Figure 26.1

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Lungs Gastrointestinal Kidneys Fluid Compartments tract

• Extracellular fluid ôExamples?

H O, ôFunctions Blood O2 CO 2 Nutrients 2 H2O, Nitrogenous plasma Ions Ions wastes • Route in and out of cell öOsmosis is the primary force for movement O CO H O Nitrogenous Interstitial 2 2 Nutrients 2 Ions • Lubricant wastes fluid • Solvent • Acid-base balance

Intracellular fluid in tissue cells

Figure 26.3

Composition of Body Fluids Blood plasma Interstitial fluid • Intracellular fluid ECF and ICF composition varies Na + Sodium ôECF K+ Potassium • All similar, except higher protein content in plasma Ca 2+ Calcium öMajor cation: Na + Mg 2+ Magnesium öMajor anion: Cl –

– HCO 3 Bicarbonate ôICF: Cl – Chloride • Low Na + and Cl – 2– + HPO 4 Hydrogen • Major cation: K phosphate – 2– • Major anions: proteins and HPO SO 4 Sulfate 4

Figure 26.2

Composition of Body Fluids Water Balance

• Electrolytes • Water intake = water output = 2500 ml/day – Dissociate into ions in water – Water intake • Measure the number of electrical charges in a liter • Gastrointestinal tract = 1,500 ml/day – Milliequivalents per liter (mEq/L) • Absorbed from food = 750 ml/day • Metabolism = 250 ml/day – Water output • Evaporation = 200 ml/day • Exhaled breath = 700 ml/day • Gastrointestinal tract = 100 ml/day • Urine = 1,500 ml/day

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Regulation of Water Intake and Loss

100 ml Feces 4% • Metabolism 10% 250 ml Sweat 8% Carefully regulated 200 ml – Insensible losses Influences blood pressure and cytoplasmic volume Foods 30% 750 ml 700 ml via skin and lungs 28% 2500 ml

Urine 60% Beverages 60% 1500 ml 1500 ml

Average intake Average output per day per day

Figure 26.4

Regulation of Water Intake and Loss Regulation of Water Intake and Loss

• Obligatory water loss • Thirst mechanism – Expired air, perspiration, fecal moisture, urine output (minimum – Driving force for water intake 400ml/day) • Response may be modified by behavior • Independent of hydration status! – Hypothalamic thirst center osmoreceptors stimulated by • Increased plasma osmolality of 2–3% • Substantial decrease in blood volume or pressure – Results in reduced salivary gland function • Dry mouth • Sensation of thirst

Regulation of Water Intake and Loss Plasma osmolality Plasma volume* Blood pressure

Saliva Osmoreceptors Granular cells • Drinking water → inhibition of the thirst center in hypothalamus in kidney Renin-angiotensin • Inhibitory feedback signals include Dry mouth mechanism Angiotensin II – Relief of dry mouth

Hypothalamic – Activation of stomach and intestinal stretch thirst center

receptors Sensation of thirst; person takes a drink

Water moistens mouth, throat; stretches stomach, Initial stimulus intestine Physiological response Result Water absorbed Increases, stimulates from GI tract Reduces, inhibits

Plasma osmolality (*Minor stimulus)

Figure 26.5

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Regulation of Water Intake and Loss Regulation of Water Intake and Loss

• Endocrine function • Endocrine function – ADH – Aldosterone • Increases water reabsorption = reduces blood osmotic • Increases reabsorption of sodium, chloride, and water pressure – Increases blood volume = increases blood pressure • Hypothalamic osmoreceptors trigger or inhibit release – No change in blood osmotic pressure because water and sodium move together • Released in response to: • Released in response to decreases in blood pressure – Increases in blood osmolarity (primary trigger) – Large changes in blood volume or pressure » e.g. fever, sweating, vomiting, diarrhea, blood loss, burns

Fluid Shifts Regulation of ECF Movement

• Extracellular fluid distribution is dynamic • Movement from capillaries mediated by • Interstitial fluid formation is continuous hydrostatic and osmotic pressures • Fluid distribution is a balance of forces – Capillary hydrostatic – Interstitial osmotic – Interstitial hydrostatic – Capillary osmotic

Edema

HP = hydrostatic pressure • Due to fluid pressing against a wall • “Pushes” • Atypical accumulation of interstitial fluid • Arteriole Venule In capillary (HP c) • Pushes fluid out of capillary ó Causes Interstitial fluid • 35 mm Hg at arterial end and 17 mm Hg at venous end of capillary in this example ó Increased flow of fluid out of the blood or impaired Capillary • In interstitial fluid (HP if ) lymphatic drainage Net HP—Net OP Net HP—Net OP • Pushes fluid into capillary (35—0) —(26—1) (17—0) —(26—1) • 0 mm Hg in this example ô ↑ Blood pressure ô ↑ Proteins in interstitial fluid Net Net OP = osmotic pressure • Due to presence of nondiffusible ↓Plasma proteins HP OP Net Net ô 35 25 solutes (e.g., plasma proteins) HP OP • “Sucks” Lymphatic obstruction mm mm 17 25 ô • In capillary (OP c) mm mm • Pulls fluid into capillary • 26 mm Hg in this example • In interstitial fluid (OP if ) • Pulls fluid out of capillary NFP (net filtration pressure) NFP is -8 mm Hg; • 1 mm Hg in this example is 10 mm Hg; fluid moves out fluid moves in

Remember this?

Figure 19.17

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Edema Edema

• ↑ Blood pressure • ↓ Plasma proteins ó More tissue fluid at arteriolar end of capillary ó Decreases osmotic return of water into venous end of capillary ó Hypertension ó Liver disease • ↑ Proteins in interstitial fluid ó Kidney disease Malnutrition ó Decreases osmotic return of water into venous end of capillary ó ó Inflammation • Lymphatic obstruction ó Allergic reaction ó Parasites ó Elephantiasis ó Tumor

Dehydration Dehydration

• Fluid loss exceeds fluid intake • Fluid loss exceeds fluid intake – Extracellular osmolarity exceeds intracellular – Causes osmolarity • Hemorrhage, severe burns, prolonged vomiting or • Fluid moves into ECF compartment diarrhea, profuse sweating, water deprivation, diuretic abuse – Cell volume reduction = compromised function – Symptoms • Thirst, dry flushed skin, oliguria – Consequences • May lead to weight loss, mental confusion, hypovolemic shock, and electrolyte imbalances

Hypotonic Hydration

• A.K.A. Water intoxication 1 Excessive 2 ECF osmotic 3 Cells lose – Causes loss of H 2O pressure rises H O to ECF 2 • Renal failure or rapid excessive water intake from ECF by osmosis; cells shrink

(a) Mechanism of dehydration

Figure 26.7a

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Hypotonic Hydration

ECF is diluted

1 Excessive 2 ECF osmotic 3 H2O moves Hyponatremia H2O enters pressure falls into cells by the ECF osmosis; cells swell Net osmosis into tissue cells

Swelling, perhaps bursting of cells

Severe metabolic disturbances (nausea, vomiting, muscular cramping, cerebral edema) (b) Mechanism of hypotonic hydration

Possible death

Figure 26.7b

Electrolytes

• Salts, acids and bases • Balance must be maintained between… – Ingestion to add materials – Excretion to remove materials • Kidneys play a key role

Electrolytes Electrolytes

• Importance of electrolytes • Pica – Controlling fluid movements – Eating non-food substances, often due to mineral – Excitability of cells deficiency • – Membrane permeability Examples: Consumption of chalk, clay, match tips

In addition to these general considerations, each electrolyte has its own specific physiological effects

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Membrane Potential Membrane Potential

• Polarized across resting membrane – Inside negative relative to outside – Nerst equation allows us to calculate the potential across the membrane for any single ion

Membrane Potential Membrane Potential

• Depolarization • Calcium and magnesium are normally non- – Reduced membrane potential diffusing • Smaller stimulus needed to reach threshold – Changes in distribution do not directly affect • Hyperpolarization membrane potential – Increased membrane potential • Changes in concentration influence sodium • Larger stimulus required to reach threshold channel permeability

Membrane Potential Sodium

• Major extracellular cation Hyperpolarized Depolarized – Normal: 135-145 mEq/L Hyponatremia Hypernatremia – Na + leaks into cells and is pumped out against its Hypokalemia Hyperkalemia electrochemical gradient • Hypercalcemia Hypocalcemia Primary roles – Necessary for impulse transmission Hypermagnesemia Hypomagnesemia • Nervous and muscle tissue Hyperchloremia Hypochloremia – Primary regulator of ECF volume

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Sodium Sodium

• Variations in Na + can alter ECF volume • Hyponatremia – – Imbalances summary Hypervolemic • Replacing water (not electrolytes) after perspiration • Hypervolemic hyponatremia • Freshwater near-drowning – Gain of water only (dilutes sodium) • Syndrome of Inappropriate ADH Secretion (SIADH) • Hypovolemic hyponatremia • Renal failure – Loss sodium first then water follows (more sodium lost) – Hypovolemic • Hypervolemic hypernatremia • GI disease (decreased intake, loss through vomiting and – Gain of sodium and water (more sodium gained) diarrhea) • Hypovolemic hypernatremia • Aldosterone deficiency (Addison’s) – Loss of sodium and water (more water lost) • Diuretics

Sodium Sodium

• Hyponatremia • Hypernatremia – Symptoms – Not as common • Feeling of “impending doom” – Unconscious or confused patients higher risk • Abdominal cramps • Hypervolemic • Nausea and vomiting – Saltwater near drowning • Anorexia – Excessive salt intake • BP changes – Hyperaldosteronism • Cellular swelling • Hypovolemic hypernatremia • Cerebral edema possible – Decreased fluid intake – Lethargy, confusion – Excessive water loss (fever) – Muscle twitching or convulsions

Sodium Potassium

ó Hypernatremia • Major intracellular cation ôSymptoms – Normal range 3.5-5.5 mEq/L ˜Reduced interstitial fluid – Normal kidney function required for balance öDry sticky mucous membranes, intense thirst, dry tongue ˜Reduced perspiration • Importance öFlushed skin – Affects RMP in neurons and muscle cells ˜Cerebral cellular dehydration • Especially cardiac muscle öLethargy, muscle weakness, twitching, seizures öSevere cases: disorientation, delusions, hallucinations – Maintenance of cellular volume ˜Altered neuromuscular activity – pH regulation öMuscle weakness, twitching ˜Low blood volume öHypotension, tachycardia

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Potassium Potassium

• Regulation • Acid-base balance – Aldosterone – H+ shifts in and out of cells in response to pH • Stimulates K + secretion and Na + reabsorption • Leads to corresponding potassium shifts in the opposite – Dietary sources direction to maintain cation balance • • Very important since potassium is poorly stored in the Shifts may cause changes in ECF potassium levels body

Potassium Potassium

• Hypokalemia • Hypokalemia – Causes – • GI losses Symptoms – Intestinal fistula, NG suctioning, vomiting, diarrhea • Slowed smooth muscle contraction • Redistribution – Anorexia, constipation, GI distention – Alkalosis, insulin administration • Slowed skeletal muscle contraction • Medications – Muscle weakness, cramping, paralysis – Diuretics, natural licorice (mimics aldosterone), steroids, certain • Decreased myocardial contraction drugs (amphotericin B is an antifungal) – • Disorders Dysrhythmias, hypotension, weak pulses – Hyperaldosteronism, Cushing’s, acute renal failure, alcoholism, liver disease

Potassium Potassium

• Hyperkalemia • Hyperkalemia – Causes – Symptoms • Retention disorders • GI effects – Renal failure (↓ GFR), Addison’s disease, hypoaldosteronism, – Nausea, explosive diarrhea, intestinal colic, cramping transfusion with old RBCs (potassium is released as RBCs • Musculoskeletal effects rupture) – Paresthesia (“pins and needles” sensation), muscle weakness, • Releases of intracellular potassium muscle cramps, paralysis – Acidosis, trauma, severe burns, severe infection • Cardiac effects • Excessive administration – Dysrhythmias (arrhythmias), hypotension, cardiac arrest, – Oral or IV conduction abnormalities, ectopic foci

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Calcium Calcium

óECF levels closely regulated • Distribution ô8.5-10.5 mg/dl – Most is stored in bone ˜Nerve and muscle function – Serum ˜Blood clotting • Ionized form is active form (50%) ˜Tissue development • Plasma protein bound pH determines equilibrium ˜Enzyme activation

Hypocalcemia (low blood Ca 2+ ) stimulates Calcium parathyroid glands to release PTH.

Rising Ca 2+ in • PTH blood inhibits PTH release. – Influences Ca 2+ in bone, kidneys, and GI tract Bone – Released when plasma Ca 2+ concentration is low Calcium is reabsorbed • In the kidney and 1 PTH activates Activates osteoclasts 2+ phosphate is selectively osteoclasts: Ca 3S – and PO 4 released Release calcium and phosphate from bone excreted into blood. • Stimulates intestinal Ca 2+ uptake 2 PTH increases Kidney Ca 2+ reabsorption • in kidney Increases renal tubule reabsorption tubules. 3 PTH promotes • kidney’s activation of vitamin D, Calcitonin which increases Ca 2+ absorption – Inhibits osteoclasts from food. – Not as important in humans as PTH Intestine Ca 2+ ions PTH Molecules Bloodstream

Figure 16.12

Calcium Calcium

• Hypocalcemia • Hypocalcemia – Causes – Symptoms • Inactive parathyroid glands • Increased nerve cell permeability and excitability • Removal of parathyroid glands – Tetany, carpopedal spasms, convulsions, seizures • Low dietary calcium • Tingling in fingers, mouth and feet • Renal failure • Trousseau’s sign • Reduced intestinal absorption • Cardiac arrhythmias

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Calcium Calcium

• Hypercalemia • Hypercalemia – Causes – Symptoms • Overactive parathyroid gland • Decreased neuromuscular excitability • Excess vitamin D intake – Muscle weakness – • Acidosis Poor coordination • • Leukemia Anorexia • Constipation • Renal calculi • Cardiac arrest

Magnesium Magnesium

• Second most abundant intracellular cation • Hypomagnesemia – 1.5 – 2.5 mEq/liter – Causes – Activates many enzyme systems – Carbohydrate and protein metabolism • Critical illnesses – Important to neuromuscular function • Alcohol withdrawal • Location • Malnutrition followed by nourishment – Skeleton • Severe GI fluid losses – Intracellularly • Heart, skeletal muscle, liver – Serum • Ionized and protein bound

Magnesium Magnesium

• Hypomagnesemia • Hypermagnesemia – Symptoms – Causes • Hyperexcitability with muscular weakness • Renal failure • Tremors • Untreated DKA • Athetoid movements • Excessive administration • Tetany • Laryngeal stridor • Mood alterations • Cardiac arrhythmias

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Magnesium Phosphate

• Hypermagnesemia • Normal 2.5-4.5 mg/dl – Symptoms – Phosphorus essential to mitochondrial function, • Acute elevations RBCs, and nervous system function – Depresses CNS • Mild elevation – Vasodilation → hypotension • Moderate to high elevations – Lethargy, dysarthria (unclear articulation of speech), drowsiness – Loss of deep tendon reflexes – Muscular weakness

Phosphate Phosphate

• Hypophosphatemia • Hypophosphatemia – Causes – Symptoms • Hyperventilation • Neurologic symptoms • Alcohol withdrawal – Irritability, apprehension, weakness, numbness, paresthesia, confusion, seizures, coma • Poor dietary intake • Tissue anoxia • DKA • Infection • Major thermal burns • Muscle pain

Phosphate Acid-Base Balance

• Mechanisms that control acid-base homeostasis óHyperphosphatemia – Acids and bases continually enter and leave body ôCauses – Hydrogen ions also result from metabolic activity ˜Renal failure ˜Chemotherapy ˜Excessive dietary intake ˜Muscle necrosis ôSymptoms ôAltered mentation and cardiac abnormalities

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Acid-Base Balance Acid-Base Balance

óAcids óStrong acids ôHydrogen ion donors ôDissociate completely in water ôDissociation = H + and a conjugate base ôCan dramatically affect pH óBases óWeak acids ôHydrogen ion acceptors ôDissociate partially in water ôEfficient at preventing pH changes pH determined by hydrogen ion concentration

HCI H2CO 3 Acid-Base Balance

óChemical buffer ôSystem of two or more compounds that act to resist pH changes when acid or base is added ôUsually consist of a weak acid and its conjugate base

(a) A strong acid such as (b) A weak acid such as

HCI dissociates H2CO 3 does not completely into its ions. dissociate completely.

Figure 26.11

Acid-Base Balance Acid-Base Balance

• Mechanisms for neutralizing or eliminating H + • Buffers 1. Sodium bicarbonate – carbonic acid buffer system – Sodium bicarbonate-carbonic acid • 2. Phosphate buffer system Mixture of H 2CO 3 (weak acid) and NaHCO 3 – + - 3. Hemoglobin-oxyhemoglobin system NaHCO 3 ‰ Na + HCO 3 (conjugate base) • Buffers ICF and ECF 4. Protein buffer system • Present in all body fluids

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Acid-Base Balance Acid-Base Balance

• Buffers • Buffers – Sodium bicarbonate-carbonic acid – Sodium bicarbonate-carbonic acid • If acid is added: • If base is added – – + – + HCO 3 ties up H and forms H 2CO 3 Causes H 2CO 3 to dissociate and donate H » » + – Example: HCl + NaHCO 3 → H2CO 3 + NaCl H ties up the base (e.g. OH ) » + » Prevents accumulation of H Example: NaOH + H 2CO 3 → NaHCO 3 + H 2O » pH decreases only slightly » OH- does not accumulate – » H2CO 3 is easily converted to CO 2 and H 2O pH rises only slightly » – Removed by respiratory system H2CO 3 supply is almost limitless from CO 2 produced by cellular respiration

Acid-Base Balance Acid-Base Balance

• Buffers • Buffers – Sodium bicarbonate-carbonic acid – Sodium bicarbonate-carbonic acid • Normal body processes tend to acidify blood • Plasma bicarbonate highly regulated by kidneys – More base is needed • Plasma carbonic acid regulated by lungs – Normal ratio is 20:1 (NaHCO 3:H 2CO 3) – Produces pH of 7.4

Acid-Base Balance Acid-Base Balance

• Buffers • Buffers – Phosphate buffer system – Phosphate buffer system • Takes place in kidney tubular fluids and RBC’s • Components are sodium salts of: • • – Action is nearly identical to the bicarbonate buffer Dihydrogen phosphate (H 2PO 4 ) – Weak acid • 2– Monohydrogen phosphate (HPO 4 ) – Conjugate base • Effective buffer in urine and ICF (RBCs) – Where phosphate concentrations are high

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Acid-Base Balance Acid-Base Balance

• Buffers • Buffers – Phosphate buffer system – Hemoglobin-oxyhemoglobin buffer system • Addition of acid • Second buffer in RBCs – HCl + Na 2HPO 4 → NaH 2PO 4 + NaCl • Don’t need to know any more details for our purposes • Addition of base – NaOH + NaH 2PO 4 → Na 2HPO 4 + H 2O

Both reactions prevent large changes in pH

Acid-Base Balance Acid-Base Balance

• Buffers • Buffers – Protein buffer system – Protein buffer system • Most abundant buffer of the body • Protein molecules are amphoteric – • Active over wide pH range Can function as both acids and bases • When pH rises – Carboxyl (COOH) groups release H + • When pH falls – + NH 2 groups bind H

Acid-Base Balance Acid-Base Balance

• Buffers • Respiratory and renal regulation – Protein buffer system – Respiratory regulation • • + A single protein molecule may function as an acid or a Regulates CO 2 and H base – Renal regulation – Depends upon the pH in the solution • Three actions 1. Acidification of urine 2. Reabsorption of bicarbonate 3. Buffering effects of phosphate and ammonia in filtrate

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Acid-Base Balance Acid-Base Balance

• Respiratory acidosis • Respiratory acidosis – Carbonic acid excess, distinguished by CO2 – Compensation by kidneys – Conditions which impair ventilation • Work to reestablish 20:1 ratio of bicarbonate : carbonic • Drug overdose (sedatives) acid – • Kidneys increase formation of NaHCO 3 and excretion of Chest or head injuries ammonium ion • Pulmonary edema – Example • Sudden airway obstruction - pH = 7.30 pCO 2 = 55 HCO 3 = 27 • COPD

Acid-Base Balance Acid-Base Balance

• Respiratory acidosis • Respiratory alkalosis – – Temporary disturbance Carbonic acid deficit, characterized by fall in CO 2 • Increased respiratory rate – Causes of hyperventilation – Signs and symptoms of respiratory acidosis • Anxiety • Dilation of cerebral blood vessels • Early COPD • Cerebral edema and depressed CNS • Early aspirin toxicity • Increased acid and ammonia in urine • Excessive mechanical ventilation • Hyperkalemia • High altitude • Arrhythmias

Acid-Base Balance Acid-Base Balance

• Respiratory alkalosis • Respiratory alkalosis – Compensation involves – Symptoms • - • HCO 3 excretion Cerebral vasoconstriction • H+ retention • Lightheadedness – Example • Lack of ability to concentrate - • Tingling in hands and feet pH = 7.48 pCO 2 = 30 HCO 3 = 20 • Carpopedal spasms • Altered consciousness

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Acid-Base Balance Acid-Base Balance

• Metabolic acidosis • Metabolic acidosis • Loss of base – Respiratory compensation – Kidney disease • Hyperventilation to blow of CO 2 – Severe diarrhea or prolonged vomiting – Kussmaul (deep, labored, fast) breathing • Excess acid accumulation – Renal compensation – Diabetes • – Lactic acid If possible – + + – Impaired renal excretion Reabsorb NaHCO 3 and secrete H and NH 4 – Example - pH = 7.32 pCO 2 = 29 HCO 3 = 17

Acid-Base Balance Acid-Base Balance

• Metabolic acidosis • Metabolic alkalosis – Signs and symptoms • Excess accumulation of base • Headache, nausea, vomiting – Increased consumption (antacid abuse) • Confusion and drowsiness • Depletion of acid – • Increased respiratory rate and depth Excessive vomiting, gastric suction, diuretics • Hyperkalemia – Colic, diarrhea, muscular weakness, tingling and numbness in extremities • Hypercalcemia – More calcium is ionized

Acid-Base Balance Acid-Base Balance

• Metabolic alkalosis • Metabolic alkalosis – Compensation – Signs and symptoms • Respiratory • Tingling of fingers and toes – Hypoventilation • Dizziness » Hypoxic drive of chemoreceptors limits this response • Tetany • Kidneys • Carpopedal spasms – If possible » + Secretes NaHCO 3 and retains H – Signs mainly due to decreased ionized calcium Example and increased membrane permeability - pH = 7.50 pCO 2 = 50 HCO 3 = 32