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

Body Fluids Fluid Compartments

• 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
Examples?
Functions Blood
plasma
O2 CO2 Nutrients H2O,
Ions
H2O,
Ions
Nitrogenous
wastes
• Route in and out of cell
Osmosis is the primary force for movement
O2 CO2 Nutrients H2O Ions Nitrogenous
• Lubricant Interstitial
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 ECF
K+ Potassium • All similar, except higher protein content in plasma
Ca2+ Calcium Major cation: Na+
Mg2+ Magnesium Major anion: Cl–
HCO3– Bicarbonate ICF:
Cl– Chloride • Low Na+ and Cl–
HPO42– Hydrogen • Major cation: K+
phosphate
SO42– Sulfate • Major anions: proteins and HPO4–

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

1500 ml Urine 60%

Beverages 60% 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:
– Increases in blood osmolarity (primary trigger)
• Released in response to decreases in blood pressure
– 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
• In capillary (HPc)
Arteriole Venule
Interstitial fluid
• Pushes fluid out of capillary Causes
• 35 mm Hg at arterial end and
17 mm Hg at venous end of
capillary in this example
Increased flow of fluid out of the blood or impaired
Net HP—Net OP
Capillary
Net HP—Net OP
• In interstitial fluid (HPif)
• Pushes fluid into capillary
lymphatic drainage
(35—0)—(26—1) (17—0)—(26—1) • 0 mm Hg in this example ↑ Blood pressure
↑ Proteins in interstitial fluid
Net Net OP = osmotic pressure
HP OP Net Net
• Due to presence of nondiffusible ↓Plasma proteins
35 25 solutes (e.g., plasma proteins)
mm mm
HP
17
OP
25
• “Sucks” Lymphatic obstruction
• In capillary (OPc)
mm mm • Pulls fluid into capillary
• 26 mm Hg in this example
• In interstitial fluid (OPif)
• 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

More tissue fluid at arteriolar end of capillary Decreases osmotic return of water into venous end of capillary
Hypertension Liver disease
• ↑ Proteins in interstitial fluid Kidney disease
Malnutrition
Decreases osmotic return of water into venous end of capillary
Inflammation • Lymphatic obstruction
Allergic reaction Parasites
Elephantiasis
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
– Cell volume reduction = compromised function
abuse
– 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 H2O pressure rises H2O to ECF
from ECF • Renal failure or rapid excessive water intake
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
– Reduced membrane potential
• Smaller stimulus needed to reach threshold
• Hyperpolarization
– Increased membrane potential
• Larger stimulus required to reach threshold
• Calcium and magnesium are normally non-
diffusing
– Changes in distribution do not directly affect
membrane potential
• Changes in concentration influence sodium
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
Hypernatremia • Major intracellular cation
Symptoms – Normal range 3.5-5.5 mEq/L
Reduced interstitial fluid – Normal kidney function required for balance
Dry sticky mucous membranes, intense thirst, dry tongue
Reduced perspiration • Importance
Flushed skin
– Affects RMP in neurons and muscle cells
Cerebral cellular dehydration
Lethargy, muscle weakness, twitching, seizures
• Especially cardiac muscle
Severe cases: disorientation, delusions, hallucinations – Maintenance of cellular volume
Altered neuromuscular activity – pH regulation
Muscle weakness, twitching
Low blood volume
Hypotension, 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
drugs (amphotericin B is an antifungal)
• Decreased myocardial contraction
– Dysrhythmias, hypotension, weak pulses
• Disorders
– 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
ECF levels closely regulated • Distribution
8.5-10.5 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 Ca2+) stimulates

Calcium parathyroid glands to release PTH.

Rising Ca2+ in
• PTH blood inhibits
PTH release.

– Influences Ca2+ in bone, kidneys, and GI tract Bone

– Released when plasma Ca2+ concentration is low Calcium is reabsorbed

In the kidney and 1 PTH activates
• Activates osteoclasts phosphate is selectively osteoclasts: Ca2+
and PO43S released
– Release calcium and phosphate from bone excreted into blood.
• Stimulates intestinal Ca2+ uptake 2 PTH increases
Ca2+ reabsorption
Kidney

• Increases renal tubule reabsorption in kidney

tubules.
3 PTH promotes
• Calcitonin kidney’s activation of vitamin D,
which increases Ca2+ absorption
from food.
– Inhibits osteoclasts
– Not as important in humans as PTH Intestine

Ca2+ 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
– Poor coordination
• Acidosis
• Leukemia • Anorexia
• Constipation
• Renal calculi
• Cardiac arrest

Magnesium Magnesium
• Second most abundant intracellular cation • Hypomagnesemia
– 1.5 – 2.5 mEq/liter
– Activates many enzyme systems
– Causes
– 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
Hyperphosphatemia – Acids and bases continually enter and leave body
Causes – Hydrogen ions also result from metabolic activity
Renal failure
Chemotherapy
Excessive dietary intake
Muscle necrosis
Symptoms
Altered mentation and cardiac abnormalities

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Acid-Base Balance Acid-Base Balance

Acids Strong acids
Hydrogen ion donors Dissociate completely in water
Dissociation = H+ and a conjugate base Can dramatically affect pH
Bases Weak acids
Hydrogen ion acceptors Dissociate partially in water
Efficient at preventing pH changes
pH determined by hydrogen ion concentration

HCI H2CO3 Acid-Base Balance

Chemical buffer
System of two or more compounds that act to
resist pH changes when acid or base is added
Usually consist of a weak acid and its conjugate base

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

HCI dissociates H2CO3 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 H2CO3 (weak acid) and NaHCO3
– NaHCO3 Na+ + HCO3- (conjugate base)
3. Hemoglobin-oxyhemoglobin system
• Buffers ICF and ECF
4. Protein buffer system • Present in all body fluids

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Acid-Base Balance
• Buffers • Buffers
– Sodium bicarbonate-carbonic acid
• If acid is added:
– HCO3– ties up H+ and forms H2CO3
» Example: HCl + NaHCO3 → H2CO3 + NaCl
» Prevents accumulation of H+
» pH decreases only slightly
– H2CO3 is easily converted to CO2 and H2O
» Removed by respiratory system
Acid-Base Balance
• Buffers • Buffers
– Sodium bicarbonate-carbonic acid
• Normal body processes tend to acidify blood
– More base is needed
– Normal ratio is 20:1 (NaHCO3:H2CO3)
– Produces pH of 7.4
Acid-Base Balance
• Buffers • Buffers
– Phosphate buffer system
• Takes place in kidney tubular fluids and RBC’s
• Action is nearly identical to the bicarbonate buffer
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Acid-Base Balance
– Sodium bicarbonate-carbonic acid
• If base is added
– Causes H2CO3 to dissociate and donate H+
» H+ ties up the base (e.g. OH–)
» Example: NaOH + H2CO3 → NaHCO3 + H2O
» OH- does not accumulate
» pH rises only slightly
– H2CO3 supply is almost limitless from CO2 produced by cellular
respiration
Acid-Base Balance
– Sodium bicarbonate-carbonic acid
• Plasma bicarbonate highly regulated by kidneys
• Plasma carbonic acid regulated by lungs
Acid-Base Balance
– Phosphate buffer system
• Components are sodium salts of:
• Dihydrogen phosphate (H2PO4–)
– Weak acid
• Monohydrogen phosphate (HPO42–)
– 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 + Na2HPO4 → NaH2PO4 + NaCl • Don’t need to know any more details for our purposes
• Addition of base
– NaOH + NaH2PO4 → Na2HPO4 + H2O

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
– Can function as both acids and bases
• Active over wide pH range
• When pH rises
– Carboxyl (COOH) groups release H+
• When pH falls
– NH2 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 CO2 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 NaHCO3 and excretion of
• Chest or head injuries ammonium ion
• Pulmonary edema – Example
• Sudden airway obstruction
pH = 7.30 pCO2 = 55 HCO3- = 27
• COPD

Acid-Base Balance Acid-Base Balance

• Respiratory acidosis • Respiratory alkalosis
– Temporary disturbance – Carbonic acid deficit, characterized by fall in CO2
• 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
• HCO3- excretion • Cerebral vasoconstriction
• H+ retention • Lightheadedness
– Example • Lack of ability to concentrate
pH = 7.48 pCO2 = 30 HCO3- = 20 • Tingling in hands and feet
• 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 CO2
– Severe diarrhea or prolonged vomiting
– Kussmaul (deep, labored, fast) breathing
• Excess acid accumulation
– Diabetes
– Renal compensation
– Lactic acid • If possible
– Impaired renal excretion – Reabsorb NaHCO3 and secrete H+ and NH4+
– Example
pH = 7.32 pCO2 = 29 HCO3- = 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 NaHCO3 and retains H+
Signs mainly due to decreased ionized calcium
– Example and increased membrane permeability
pH = 7.50 pCO2 = 50 -
HCO3 = 32

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