Fluid, Electrolyte, and Acid-Base Balance

Body Water Content

•   Infants: 73% or more water (low body fat, low bone mass)

•   Adult males: ~60% water

•   Adult females: ~50% water (higher fat content, less skeletal muscle mass)

•   Water content declines to ~45% in old age

Fluid Compartments

•   Total body water = 40 L

1.  Intracellular fluid (ICF) compartment: 2/3 or 25 L in cells

2.  Extracellular fluid (ECF) compartment: 1/3 or 15 L

•   Plasma: 3 L

•   Interstitial fluid (IF): 12 L in spaces between cells

•   Other ECF: lymph, CSF, humors of the eye, synovial fluid, serous fluid, and gastrointestinal secretions

Composition of Body Fluids

•   Water: the universal solvent

•   Solutes: nonelectrolytes and electrolytes

•    Nonelectrolytes: most are organic

•   Do not dissociate in water: e.g., glucose, lipids, creatinine, and urea

Composition of Body Fluids

•   Electrolytes

•    Dissociate into ions in water; e.g., inorganic salts, all acids and bases, and some proteins

•    The most abundant (most numerous) solutes

•    Have greater osmotic power than nonelectrolytes, so may contribute to fluid shifts

•    Determine the chemical and physical reactions of fluids

 Electrolyte Concentration

•   Expressed in milliequivalents per liter (mEq/L), a measure of the number of electrical charges per liter of solution

mEq/L = ion concentration (mg/L)          ´  # of electrical charges
      atomic weight of ion (mg/mmol)         on one ion

 Electrolyte Concentration

•   For single charged ions (e.g. Na⁺), 1 mEq = 1 mOsm

•   For bivalent ions (e.g. Ca²⁺), 1 mEq = 1/2 mOsm

Extracellular and Intracellular Fluids

•   Each fluid compartment has a distinctive pattern of electrolytes

•   ECF

•    All similar, except higher protein content of plasma

•   Major cation: Na⁺

•   Major anion: Cl^–

Extracellular and Intracellular Fluids

•   ICF:

•     Low Na⁺ and Cl^–

^•      Major cation: K⁺

•    Major anion HPO₄^2–

Extracellular and Intracellular Fluids

•   Proteins, phospholipids, cholesterol, and neutral fats make up the bulk of dissolved solutes

•    90% in plasma

•    60% in IF

•    97% in ICF

Fluid Movement Among Compartments

•   Regulated by osmotic and hydrostatic pressures

•   Water moves freely by osmosis; osmolalities of all body fluids are almost always equal

•   Two-way osmotic flow is substantial

•   Ion fluxes require active transport or channels

•   Change in solute concentration of any compartment leads to net water flow

Water Balance and ECF Osmolality

•   Water intake = water output = 2500 ml/day

•   Water intake: beverages, food, and metabolic water

•   Water output: urine, insensible water loss (skin and lungs), perspiration, and feces

Regulation of Water Intake

•   Thirst mechanism is the driving force for water intake

•   The hypothalamic thirst center osmoreceptors are stimulated by

•     ¯ Plasma osmolality of 2–3%

•     Angiotensin II or baroreceptor input

•     Dry mouth

•     Substantial decrease in blood volume or pressure

Regulation of Water Intake

•   Drinking water creates inhibition of the thirst center

•   Inhibitory feedback signals include

•    Relief of dry mouth

•    Activation of stomach and intestinal stretch receptors

Regulation of Water Output

•   Obligatory water losses

•    Insensible water loss: from lungs and skin

•    Feces

•    Minimum daily sensible water loss of 500 ml in urine to excrete wastes

•   Body water and Na⁺ content are regulated in tandem by mechanisms that maintain cardiovascular function and blood pressure

Regulation of Water Output: Influence of ADH

•   Water reabsorption in collecting ducts is proportional to ADH release

•   ¯ ADH ® dilute urine and ¯ volume of body fluids

•   ­ ADH ® concentrated urine

Regulation of Water Output: Influence of ADH

•   Hypothalamic osmoreceptors trigger or inhibit ADH release

•   Other factors may trigger ADH release via large changes in blood volume or pressure, e.g., fever, sweating, vomiting, or diarrhea; blood loss; and traumatic burns

Disorders of Water Balance: Dehydration

•   Negative fluid balance

•    ECF water loss due to: hemorrhage, severe burns, prolonged vomiting or diarrhea, profuse sweating, water deprivation, diuretic abuse

•    Signs and symptoms: thirst, dry flushed skin, oliguria

•    May lead to weight loss, fever, mental confusion, hypovolemic shock, and loss of electrolytes

Disorders of Water Balance: Hypotonic Hydration

•   Cellular overhydration, or water intoxication

•   Occurs with renal insufficiency or rapid excess water ingestion

•   ECF is diluted ®  hyponatremia ® net osmosis into tissue cells ® swelling of cells ® severe metabolic disturbances (nausea, vomiting, muscular cramping, cerebral edema) ® possible death

Disorders of Water Balance: Edema

•   Atypical accumulation of IF fluid ® tissue swelling

•   Due to anything that increases flow of fluid out of the blood or hinders its return

•     ­ Blood pressure

•     ­ Capillary permeability (usually due to inflammatory chemicals)

•     Incompetent venous valves, localized blood vessel blockage

•     Congestive heart failure, hypertension, ­ blood volume

Edema

•   Hindered fluid return occurs with an imbalance in colloid osmotic pressures, e.g., hypoproteinemia (¯ plasma proteins)

•    Fluids fail to return at the venous ends of capillary beds

•    Results from protein malnutrition, liver disease, or glomerulonephritis

Edema

•   Blocked (or surgically removed) lymph vessels

•    Cause leaked proteins to accumulate in IF

•    ­ Colloid osmotic pressure of IF draws fluid from the blood

•    Results in low blood pressure and severely impaired circulation

Electrolyte Balance

•   Electrolytes are salts, acids, and bases

•   Electrolyte balance usually refers only to salt balance

•   Salts enter the body by ingestion and are lost via perspiration, feces, and urine

Electrolyte Balance

•   Importance of salts

•    Controlling fluid movements

•    Excitability

•    Secretory activity

•    Membrane permeability

Central Role of Sodium

•   Most abundant cation in the ECF

•   Sodium salts in the ECF contribute 280 mOsm of the total 300 mOsm ECF solute concentration

•   Na⁺ leaks into cells and is pumped out against its electrochemical gradient

•   Na⁺ content may change but ECF Na⁺ concentration remains stable due to osmosis

Central Role of Sodium

•   Changes in plasma sodium levels affect

•    Plasma volume, blood pressure

•    ICF and IF volumes

•   Renal acid-base control mechanisms are coupled to sodium ion transport

Regulation of Sodium Balance

•   No receptors are known that monitor Na⁺ levels in body fluids

•   Na⁺-water balance is linked to blood pressure and blood volume control mechanisms

Regulation of Sodium Balance: Aldosterone

•   Na⁺ reabsorption

•    65% is reabsorbed in the proximal tubules

•    25% is reclaimed in the loops of Henle

•   Aldosterone ® active reabsorption of remaining Na⁺

•   Water follows Na⁺ if ADH is present

Regulation of Sodium Balance: Aldosterone

•   Renin-angiotensin mechanism is the main trigger for aldosterone release

•    Granular cells of JGA secrete renin in response to

•   Sympathetic nervous system stimulation

•   ¯ Filtrate osmolality

•   ¯ Stretch (due to ¯ blood pressure)

Regulation of Sodium Balance: Aldosterone

•   Renin catalyzes the production of angiotensin II, which prompts aldosterone release from the adrenal cortex

•   Aldosterone release is also triggered by elevated K⁺ levels in the ECF

•   Aldosterone brings about its effects slowly (hours to days)

Regulation of Sodium Balance: ANP

•   Released by atrial cells in response to stretch (­ blood pressure)

•   Effects

•   Decreases blood pressure and blood volume:

•    ¯ ADH, renin and aldosterone production

•    ­ Excretion of Na⁺ and water

•    Promotes vasodilation directly and also by decreasing production of angiotensin II

Influence of Other Hormones

•   Estrogens: ­ NaCl reabsorption (like aldosterone)

•    ® H₂O retention during menstrual cycles and pregnancy

•   Progesterone: ¯ Na⁺ reabsorption (blocks aldosterone)

•    Promotes Na⁺ and H₂O loss

•   Glucocorticoids: ­ Na⁺ reabsorption and promote edema

Cardiovascular System Baroreceptors

•   Baroreceptors alert the brain of increases in blood volume and pressure

•    Sympathetic nervous system impulses to the kidneys decline

•    Afferent arterioles dilate

•    GFR increases

•    Na⁺ and water output increase

Regulation of Potassium Balance

•   Importance of potassium:

•    Affects RMP in neurons and muscle cells (especially cardiac muscle)

•   ­ ECF [K⁺] ® ¯RMP ® depolarization ® reduced excitability

•   ¯ ECF [K⁺]® hyperpolarization and nonresponsiveness

Regulation of Potassium Balance

•   H⁺ shift in and out of cells

•    Leads to corresponding shifts in K⁺ in the opposite direction to maintain cation balance

•    Interferes with activity of excitable cells

Regulation of Potassium Balance

•   K⁺ balance is controlled in the cortical collecting ducts by changing the amount of potassium secreted into filtrate

•   High K⁺ content of ECF favors principal cell secretion of K⁺

•   When K⁺ levels are low, type A intercalated cells reabsorb some K⁺ left in the filtrate

 Regulation of Potassium Balance

•   Influence of aldosterone

•    Stimulates K⁺ secretion (and Na⁺ reabsorption) by principal cells

•    Increased K⁺ in the adrenal cortex causes

•   Release of aldosterone

•   Potassium secretion

Regulation of Calcium

•   Ca²⁺ in ECF is important for

•    Neuromuscular excitability

•    Blood clotting

•    Cell membrane permeability

•    Secretory activities

Regulation of Calcium

•   Hypocalcemia ® ­ excitability and muscle tetany

•   Hypercalcemia ® Inhibits neurons and muscle cells, may cause heart arrhythmias

•   Calcium balance is controlled by parathyroid hormone (PTH) and calcitonin

Influence of PTH

•   Bones are the largest reservoir for Ca²⁺ and phosphates

•   PTH promotes increase in calcium levels by targeting bones, kidneys, and small intestine (indirectly through vitamin D)

•   Calcium reabsorption and phosphate excretion go hand in hand

Influence of PTH

•   Normally 75% of filtered phosphates are actively reabsorbed in the PCT

•   PTH inhibits this by decreasing the T_m

Regulation of Anions

•   Cl^– is the major anion in the ECF

•    Helps maintain the osmotic pressure of the blood

•    99% of Cl^– is reabsorbed under normal pH conditions

•   When acidosis occurs, fewer chloride ions are reabsorbed

•   Other anions have transport maximums and excesses are excreted in urine

Acid-Base Balance

•   pH affects all functional proteins and biochemical reactions

•   Normal pH of body fluids

•    Arterial blood: pH 7.4

•    Venous blood and IF fluid: pH 7.35

•    ICF: pH 7.0

•   Alkalosis or alkalemia: arterial blood pH >7.45

•   Acidosis or acidemia: arterial pH < 7.35

Acid-Base Balance

•   Most H⁺ is produced by metabolism

•    Phosphoric acid from breakdown of phosphorus-containing proteins in ECF

•    Lactic acid from anaerobic respiration of glucose

•    Fatty acids and ketone bodies from fat metabolism

•    H⁺ liberated when CO₂ is converted to HCO₃^– in blood

Acid-Base Balance

•   Concentration of hydrogen ions is regulated sequentially by

•    Chemical buffer systems: rapid; first line of defense

•    Brain stem respiratory centers: act within 1–3 min

•    Renal mechanisms: most potent, but require hours to days to effect pH changes

Acid-Base Balance

•   Strong acids dissociate completely in water; can dramatically affect pH

•   Weak acids dissociate partially in water; are efficient at preventing pH changes

•   Strong bases dissociate easily in water; quickly tie up H⁺

•   Weak bases accept H⁺ more slowly

Chemical Buffer Systems

•   Chemical buffer: system of one or more compounds that act to resist pH changes when strong acid or base is added

1. Bicarbonate buffer system

2. Phosphate buffer system

3. Protein buffer system

Bicarbonate Buffer System

•   Mixture of H₂CO₃ (weak acid) and salts of HCO₃^– (e.g., NaHCO₃, a weak base)

•   Buffers ICF and ECF

•   The only important ECF buffer

Bicarbonate Buffer System

•   If strong acid is added:

•    HCO₃^– ties up H⁺ and forms H₂CO₃

•   HCl + NaHCO₃ ® H₂CO₃ + NaCl

•    pH decreases only slightly, unless all available HCO₃^– (alkaline reserve) is used up

•    HCO₃^– concentration is closely regulated by the kidneys

Bicarbonate Buffer System

•   If strong base is added

•    It causes H₂CO₃ to dissociate and donate H⁺

•    H⁺ ties up the base (e.g. OH^–)

•   NaOH + H₂CO₃  ® NaHCO₃ + H₂O

•    pH rises only slightly

•    H₂CO₃ supply is almost limitless (from CO₂ released by respiration) and is subject to respiratory controls

Phosphate Buffer System

•   Action is nearly identical to the bicarbonate buffer

•   Components are sodium salts of:

•    Dihydrogen phosphate (H₂PO₄^–), a weak acid

•    Monohydrogen phosphate (HPO₄^2–), a weak base

•   Effective buffer in urine and ICF, where phosphate concentrations are high

Protein Buffer System

•   Intracellular proteins are the most plentiful and powerful buffers; plasma proteins are also important

•   Protein molecules are amphoteric (can function as both a weak acid and a weak base)

•    When pH rises, organic acid or carboxyl (COOH) groups release H⁺

•    When pH falls, NH₂ groups bind H⁺

Physiological Buffer Systems

•   Respiratory and renal systems

•    Act more slowly than chemical buffer systems

•    Have more capacity than chemical buffer systems

Respiratory Regulation of H⁺

•   Respiratory system eliminates CO₂

•   A reversible equilibrium exists in the blood:

•    CO₂ + H₂O « H₂CO₃ « H⁺ + HCO₃^–

•   During CO₂ unloading the reaction shifts to the left (and H⁺ is incorporated into H₂O)

•   During CO₂ loading the reaction shifts to the right (and H⁺ is buffered by proteins)

Respiratory Regulation of H⁺

•   Hypercapnia activates medullary chemoreceptors

•   Rising plasma H⁺ activates peripheral chemoreceptors

•    More CO₂ is removed from the blood

•    H⁺ concentration is reduced

Respiratory Regulation of H⁺

•   Alkalosis depresses the respiratory center

•    Respiratory rate and depth decrease

•    H⁺ concentration increases

•   Respiratory system impairment causes acid-base imbalances

•    Hypoventilation ® respiratory acidosis

•    Hyperventilation ® respiratory alkalosis

Acid-Base Balance

•   Chemical buffers cannot eliminate excess acids or bases from the body

•    Lungs eliminate volatile carbonic acid by eliminating CO₂

•    Kidneys eliminate other fixed metabolic acids (phosphoric, uric, and lactic acids and ketones) and prevent metabolic acidosis

Renal Mechanisms of Acid-Base Balance

•   Most important renal mechanisms

•    Conserving (reabsorbing) or generating new HCO₃^–

•    Excreting HCO₃^–

•   Generating or reabsorbing one HCO₃^– is the same as losing one H⁺

•   Excreting one HCO₃^– is the same as gaining one H⁺

Renal Mechanisms of Acid-Base Balance

•   Renal regulation of acid-base balance depends on secretion of H⁺

•   H⁺ secretion occurs in the PCT and in collecting duct type A intercalated cells:

•    The H⁺ comes from H₂CO₃ produced in reactions catalyzed by carbonic anhydrase inside the cells

•    See Steps 1 and 2 of the following figure

Reabsorption of Bicarbonate

•   Tubule cell luminal membranes are impermeable to HCO₃^–

•     CO₂ combines with water in PCT cells, forming H₂CO₃

•     H₂CO₃ dissociates

•     H⁺ is secreted, and HCO₃^– is reabsorbed into capillary blood

•     Secreted H⁺ unites with HCO₃^– to form H₂CO₃ in filtrate, which generates CO₂ and H₂O

•   HCO₃^– disappears from filtrate at the same rate that it enters the peritubular capillary blood

Generating New Bicarbonate Ions

•   Two mechanisms in PCT and type A intercalated cells

•    Generate new HCO₃^– to be added to the alkaline reserve

^•    Both involve renal excretion of acid (via secretion and excretion of H⁺ or NH₄⁺

Excretion of Buffered H⁺

•   Dietary H⁺ must be balanced by generating new HCO₃^–

•   Most filtered HCO₃^– is used up before filtrate reaches the collecting duct

Excretion of Buffered H⁺

•   Intercalated cells actively secrete H⁺ into urine, which is buffered by phosphates and excreted

•   Generated “new” HCO₃^– moves into the interstitial space via a cotransport system and then moves passively into peritubular capillary blood

Ammonium Ion Excretion

•   Involves metabolism of glutamine in PCT cells

•   Each glutamine produces 2 NH₄⁺ and 2 “new” HCO₃^–

•   HCO₃^– moves to the blood and NH₄⁺ is excreted in urine

Bicarbonate Ion Secretion

•   When the body is in alkalosis, type B intercalated cells

•    Secrete HCO₃^–

•    Reclaim H⁺ and acidify the blood

Bicarbonate Ion Secretion

•   Mechanism is the opposite of the bicarbonate ion reabsorption process by type A intercalated cells

•   Even during alkalosis, the nephrons and collecting ducts excrete fewer HCO₃^– than they conserve

Abnormalities of Acid-Base Balance

•   Respiratory acidosis and alkalosis

•   Metabolic acidosis and alkalosis

Respiratory Acidosis and Alkalosis

•   The most important indicator of adequacy of respiratory function is P_CO2 level (normally 35–45 mm Hg)

•     P_CO2 above 45 mm Hg ® respiratory acidosis

•   Most common cause of acid-base imbalances

•   Due to decrease in ventilation or gas exchange

_•     Characterized by falling blood pH and rising P_CO2

Respiratory Acidosis and Alkalosis

•   P_CO2 below 35 mm Hg ® respiratory alkalosis

•    A common result of hyperventilation due to stress or pain

Metabolic Acidosis and Alkalosis

•   Any pH imbalance not caused by abnormal blood CO₂ levels

•   Indicated by abnormal HCO₃^– levels

Metabolic Acidosis and Alkalosis

•   Causes of metabolic acidosis

•    Ingestion of too much alcohol (® acetic acid)

•    Excessive loss of HCO₃^– (e.g., persistent diarrhea)

•    Accumulation of lactic acid, shock, ketosis in diabetic crisis, starvation, and kidney failure

Metabolic Acidosis and Alkalosis

•   Metabolic alkalosis is much less common than metabolic acidosis

•    Indicated by rising blood pH and HCO₃^–

•    Caused by vomiting of the acid contents of the stomach or by intake of excess base (e.g., antacids)

Effects of Acidosis and Alkalosis

•    Blood pH below 7 ® depression of CNS ® coma  ® death

•    Blood pH above 7.8 ® excitation of nervous system ® muscle tetany, extreme nervousness, convulsions, respiratory arrest

Respiratory and Renal Compensations

•   If acid-base imbalance is due to malfunction of a physiological buffer system, the other one compensates

•    Respiratory system attempts to correct metabolic acid-base imbalances

•    Kidneys attempt to correct respiratory acid-base imbalances

Respiratory Compensation

•   In metabolic acidosis

•    High H⁺ levels stimulate the respiratory centers

•    Rate and depth of breathing are elevated

•    Blood pH is below 7.35 and HCO₃^– level is low

•    As CO₂ is eliminated by the respiratory system, P_CO2 falls below normal

Respiratory Compensation

•   Respiratory compensation for metabolic alkalosis is revealed by:

•    Slow, shallow breathing, allowing CO₂ accumulation in the blood

•    High pH (over 7.45) and elevated HCO₃^– levels

Renal Compensation

_•    Hypoventilation causes elevated P_CO2

•   (respiratory acidosis)

•    Renal compensation is indicated by high HCO₃^– levels

•   Respiratory alkalosis exhibits low P_CO2 and high pH

•    Renal compensation is indicated by decreasing HCO₃^– levels

Developmental Aspects

•   Infants have proportionately more ECF than adults until about 2 years of age

•   Problems with fluid, electrolyte, and acid-base balance are most common in infancy, reflecting

•     Low residual lung volume

•     High rate of fluid intake and output

•     High metabolic rate, yielding more metabolic wastes

•     High rate of insensible water loss

•     Inefficiency of kidneys, especially during the first month

Developmental Aspects

•   At puberty, sexual differences in body water content arise as males develop greater muscle mass

•   In old age, total body water often decreases

•   Homeostatic mechanisms slow down with age

•   Elders may be unresponsive to thirst clues and are at risk of dehydration