ADVANCED PHYSIOLOGY FLUID & ELECTROLYTES PART 2 Instructor Terry Wiseth NORTHLAND COLLEGE

Na+ K+ K+ Na+ Na+ Na+ K+ K+ ELECTROLYTE BALANCE The exchange of interstitial and intracellular fluid is controlled mainly by the presence of the electrolytes sodium and potassium Na+ K+ K+ Na+ Na+ Na+ K+ K+

K+ Na+ ELECTROLYTE BALANCE Potassium is the chief intracellular cation and sodium the chief extracellular cation Because the osmotic pressure of the interstitial space and the ICF are generally equal, water typically does not enter or leave the cell K+ Na+

ELECTROLYTE BALANCE Na+ K+ K+ Na+ K+ Na+ Na+ K+ A change in the concentration of either electrolyte will cause water to move into or out of the cell via osmosis A drop in potassium will cause fluid to leave the cell whilst a drop in sodium will cause fluid to enter the cell Click to see animation Na+ K+ K+ H2O H2O Na+ H2O H2O K+ Na+ Na+ K+ H2O H2O H2O H2O

ELECTROLYTE BALANCE Na+ K+ K+ Na+ Na+ K+ Na+ K+ A change in the concentration of either electrolyte will cause water to move into or out of the cell via osmosis A drop in potassium will cause fluid to leave the cell whilst a drop in sodium will cause fluid to enter the cell Click to see animation Na+ K+ K+ H2O Na+ H2O H2O H2O Na+ K+ Na+ K+ H2O H2O H2O H2O

Na+ K+ ELECTROLYTE BALANCE Aldosterone, ANP and ADH regulate sodium levels within the body, while aldosterone can be said to regulate potassium Na+ ADH ANP K+ aldosterone

Na+ Cl- HCO3- ELECTROLYTE BALANCE Sodium (Na+) ions are the important cations in extracellular fluid Anions which accompany sodium are chloride (Cl-) and bicarbonate (HCO3-) Considered an indicator of total solute concentration of plasma osmolality Cl- HCO3-

ELECTROLYTE BALANCE Sodium ions are osmotically important in determining water movements A discussion of sodium must also include Chlorine Bicarbonate Hydrogen ions Potassium and calcium serum concentrations are also important electrolytes in the living system H2O H2O H2O H2O H2O H2O H2O H2O H2O H2O H2O H2O H2O H2O H2O

ELECTROLYTE BALANCES Click Click Hypernatremia - elevated sodium levels Hyponatremia -- lowered sodium levels Hyperkalemia -- elevated potassium levels Hypokalemia ---- lowered potassium levels Click Hypercalcemia - elevated calcium levels Hypokalcemia -- lowered calcium levels Click

HYPERNATREMIA Normal range for blood levels of sodium is app. 137 - 143 meq/liter Hypernatremia refers to an elevated serum sodium level (145 -150 meq/liter) Increased levels of sodium ions are the result of diffusion and osmosis Na+

SODIUM PRINCIPLES 1) Sodium ions do not cross cell membranes as quickly as water does H2O H2O H2O H2O H2O Na+ Na+

SODIUM PRINCIPLES 2) Cells pump sodium ions out of the cell by using sodium-potassium pumps Na+ Na+ Na+ Na+

SODIUM PRINCIPLES 3) Increases in extracellular sodium ion levels do not change intracellular sodium ion concentration Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ Na+

RESULTS OF HYPERNATREMIA 1) Water is osmotically drawn out of the cells Resulting in dehydration 2) Increase in extracellular fluid volume Intracellular fluid volume Extracellular fluid volume

CNS REACTION TO HYPERNATREMIA In the CNS tight junctions exist between endothelial cells of the capillary walls These junctions restrict diffusion from capillaries to the interstitium of the brain blood-brain barrier Increased levels of sodium ions in the blood does not result in increased sodium ions in brain interstitial fluid

CNS REACTION TO HYPERNATREMIA As the result of an osmotic gradient, water shifts from the interstitium and cells of the brain and enters the capillaries The brain tends to shrink and the capillaries dilate and possibly rupture Result is cerebral hemorrhage, blood clots, and neurological dysfunction H2O

CNS PROTECTIVE MECHANISM There is an unknown mechanism that protects the brain from shrinkage Within about 1 day Intracellular osmolality of brain cells increases in response to extracellular hyperosmolality ?

CNS PROTECTIVE MECHANISM Idiogenic osmoles accumulate inside brain cells K+, Mg+ from cellular binding sites and amino acids from protein catabolism These idiogenic osmoles create an osmotic force that draws water back into the brain and protects cells from dehydration H2O

CAUSES OF HYPERNATREMIA 1) Water loss 2) Sodium ion overload Most cases are due to water deficit due to loss or inadequate intake Infants without access to water or increased insensible water loss can be very susceptible to hypernatremia

WATER LOSS Diabetes insipidus caused by inadequate ADH or renal insensitivity to ADH results in large urinary fluid loss Increased fluid loss also occurs as the result of osmotic diuresis (high solute loads are delivered to the kidney for elimination)

WATER LOSS Diabetes mellitus results in loss of fluids as well by creating an osmotic pull (increased urine solute concentration) on water into the tubules of the kidney H2O H2O H2O Glucose Glucose Glucose H2O Glucose H2O Click to animate H2O Glucose Glucose H2O H2O Glucose Glucose H2O H2O Glucose Glucose H2O H2O Glucose

WATER LOSS High protein feedings by a stomach tube create high levels of urea in the glomerular filtrate producing an osmotic gradient the same as glucose does and increased urinary output results

SODIUM EXCESS Occurs less frequently than water loss Retention or intake of excess sodium ex: IV infusion of hypertonic sodium ion solutions Aldosterone promotes sodium and water retention by the kidney High levels of aldosterone may result in mild hypernatremia

CAUSES OF HYPERNATREMIA

TREATMENT OF HYPERNATREMIA Re-hydration is the primary objective in most cases Decreases sodium concentrations A point of concern is when and how rapid the re-hydration occurs

TREATMENT OF HYPERNATREMIA After 24 hours the brain has responded by producing idiogenic osmoles to re-hydrate brain cells If this adaptation has occurred and treatment involves a rapid infusion of dextrose for example There is danger of cerebral edema with fluid being drawn into brain tissues

TREATMENT OF HYPERNATREMIA Treatment is best handled by giving slow infusions of glucose solutions This dilutes high plasma sodium ion concentrations

TREATMENT OF HYPERNATREMIA Ideally the goal is to avoid overloading with fluid and to remove excess sodium Diuretics can be used to induce sodium and water diuresis However if kidney function is not normal peritoneal dialysis may be required

HYPONATREMIA Defined as a serum sodium ion level that is lower than normal Implies an increased ratio of water to sodium in extracellular fluid Extracellular fluid is more dilute than intracellular fluid Results in a shift of water into cells Na+

CNS RESPONSE TO HYPONATREMIA Brain cells lose osmoles creating a higher extracellular solute concentration Effect is to protect against cerebral edema by drawing water out of the brain tissue

GENERAL RESPONSE TO HYPONATREMIA Suppression of thirst Suppression of ADH secretion Both favor decreasing water ingestion and increasing urinary output

SYMPTOMS OF HYPONATREMIA Primarily neurological (net flux of water into the brain) Sodium ion levels of 125 meq / liter are enough to begin the onset of symptoms Sodium ion levels of less than 110 meq / liter bring on seizures and coma

Na+ HYPONATREMIA H O 2 Produced by: 1) A loss of sodium ions 2) Water excess Water excess can be due to: Ingestion Renal retention H O 2

DILUTIONAL EFFECT 1) Isotonic fluid loss 2) Antidiuretic hormone secretion 3) Acute or chronic renal failure 4) Potassium ion loss 5) Diuretic therapy H2O H2O H2O Na+ Na+ H2O H2O H2O H2O Na+ H2O H2O H2O H2O H2O H2O Na+ Na+ Na+ Na+ H2O H2O H2O H2O H2O H2O Na+

DILUTIONAL EFFECT 1) Isotonic fluid loss Burns, fever, hemorrhage Indirect cause of hyponatremia Any volume loss stimulates thirst and leads to increased water ingestion Thus isotonic fluid loss can cause hyponatremia not because of sodium loss but because of increased water intake

DILUTIONAL EFFECT 2) Antidiuretic hormone secretion Enhances water retention 3) Acute or chronic renal failure The kidney fails to excrete water Can lead to hyponatremia

DILUTIONAL EFFECT 4) Potassium ion loss Potassium ions are the predominant intracellular cations When they are lost they are replaced by diffusion of intracellular potassium into extracellular fluid Electrical balance is maintained by the diffusion of sodium ions into the cells in exchange for potassium ions Thus a loss of extracellular sodium is realized and hyponatremia may ensue

POTASSIUM ION LOSS cell K+ Na+ Na+ K+ K+ K+ interstitial fluid plasma 1) extracellular potassium loss 3) intracellular electrical balance is maintained by diffusion of sodium ions into cells Na+ Na+ cell K+ 2) diffusion of potassium ions into extracellular compartments K+ K+ interstitial fluid plasma

POTASSIUM ION LOSS Cell Na+ Na+ K+ Na+ K+ K+ K+ K+ K+ Click to see animation K+ K+ K+ Interstitial fluid Plasma

DILUTIONAL EFFECT 5) Diuretic therapy Common cause of hyponatremia Loss of sodium and potassium often occurs in addition to fluid loss

CAUSES OF HYPONATREMIA

REACTIONS TO HYPONATREMIA Increased ADH release Increased Thirst Decreased urinary H2O loss Increased H2O gain Osmoreceptors stimulated Click to view increased Na+ Increased Na+ Additional H2O dilutes Na+ Homeostasis Normal Na+ H2O loss concentrates Na+ Decreased Na+ Click to view decreased Na+ Decreased ADH release Decreased Thirst Increased urinary H2O loss Decreased H2O gain Osmoreceptors inhibited

K+ HYPERKALEMIA Normal serum potassium level (3-5 meq / liter) As compared to Na+ (142 meq / liter) Intracellular levels of potassium (140-150 meq / liter) This high intracellular level is maintained by active transport by the sodium-potassium pump K+

Na+ / K+ Pump Cells pump K+ ions in and Na+ ions out of the cell by using sodium-potassium pumps K+ K+ Na+ K+ K+ Na+ Na+ Na+

HYPERKALEMIA Hyperkalemia is an elevated serum potassium (K+) ion level A consequence of hyperkalemia is acidosis an increase in H+ ions in body fluids Changes in either K+ or H+ ion levels causes a compartmental shift of the other K+

HYPERKALEMIA When hyperkalemia develops potassium ions diffuse into the cell This causes a movement of H+ ions out of the cell to maintain a neutral electrical balance As a result the physiological response to hyperkalemia causes acidosis H+ K+ HYPERKALEMIA H+ K+ H+ K+ H+ K+ H+ H+ K+ H+ H+ K+ H+

HYPERKALEMIA The reverse occurs as well The body is protected from harmful effects of an increase in extracellular H+ ions (acidosis) H+ ions inside the cells are tied up by proteins (Pr -) This causes a shift of potassium ions out of the cells H+ H+ ACIDOSIS K+ H+ K+ H+ K+ H+ K+ H+ H+ K+ H+ H+ K+

HYPERKALEMIA Summarized: Hyperkalemia causes acidosis Acidosis causes hyperkalemia HYPERKALEMIA H+ K+ ACIDOSIS

HYPERKALEMIA Summarized: Hyperkalemia causes acidosis Acidosis causes hyperkalemia HYPERKALEMIA H+ K+ ACIDOSIS

SYMPTOMS OF HYPERKALEMIA Muscle contraction is affected by changes in potassium levels Hyperkalemia blocks the transmission of nerve impulses along muscle fibers Causes muscle weakness and paralysis Can cause arrhythmia's and heart conduction disturbances

CAUSES FOR HYPERKALEMIA 1) Increased input of potassium 2) Impaired excretion of potassium 3) Impaired uptake of potassium by cells

INCREASED INPUT A) Intravenous KCl infusion B) Use of K+ containing salt substitutes C) Hemolysis of RBC during blood transfusions with release of K+ D) Damaged and dying cells release K+ Burns, crush injuries, ischemia E) Increased fragility of RBC

CELLULAR-EXTRACELLULAR SHIFTS Insulin deficiency predisposes an individual to hyperkalemia Cellular uptake of K+ ions is enhanced by insulin, aldosterone and epinephrine Provides protection from extracellular K+ overload Insulin K+ K+ K+ K+ K+ Click to view animation K+

CELLULAR-EXTRACELLULAR SHIFTS Insulin deficiency represents decreased protection if the body is challenged by an excess of K+ ions In the absence of aldosterone there is loss of Na+ in the urine and renal retention of K+

HYPERKALEMIC PERIODIC PARALYSIS Inherited disorder in which serum K+ level rise periodically Caused by a shift of K+ from muscle to blood in response to ingestion of potassium or exercise Reasons for the shift are not clear Attacks are characterized by muscle weakness

RENAL INSUFFICIENCY Aldosterone has a primary role in promoting: Conservation of Na+ Secretion of K+ by the nephrons of the kidney Addison’s disease is characterized by aldosterone deficiency Thus the kidney is unable to secrete potassium at a normal rate

OLIGURIC RENAL FAILURE Kidney loses the ability to secrete K+

SPINOLACTONE Diuretic that is antagonistic to the effects of aldosterone Causes some rise in serum K+ levels by interfering with K+ secretion in the kidneys Increases may not be significant But individuals taking the diuretic are at risk if potassium is administered

TREATMENT 1) Counteract effects of K+ ions at the level of the cell membrane 2) Promotion of K+ ion movements into cells 3) Removal of K+ ions from the body

SALT INFUSIONS Infusion of calcium gluconate or NaCl solutions Immediately counteract the effects of K+ ions on the heart Effective for only 1-2 hours

SODIUM BICARBONATE NaHCO3 also reverses hyperkalemic effects on the heart If acidosis is a factor also raises the pH of body fluids

INSULIN-GLUCOSE INFUSION Insulin given with glucose Effective in about 30 minutes Has a duration of action of up to 6 hours Insulin promotes the shift of K+ ions into cells Glucose prevents insulin-induced hypoglycemia

KAYEXALATE Kayexalate (cation exchange resin) Removes K+ ions from the body by exchanging K+ for Na+ Exchange time is about 45 minutes Effective for up to 6 hours

DIALYSIS Peritoneal dialysis or hemodialysis Effectively clears the blood of high K+ levels as well

CAUSES OF HYPERKALEMIA

HYPOKALEMIA Defined as a serum K+ level that is below normal (< 3 meq / liter) Serum concentrations will decrease if: There is an intracellular flux of K+ K+ ions are lost from the gastrointestinal or urinary tract K+

H+ HCO3- K+ ALKALOSIS Alkalosis causes and is caused by hypokalemia Alkalosis is defined as a decrease of hydrogen ions or an increase of bicarbonate in extracellular fluids Opposite of acidosis H+ K+ HCO3-

ALKALOSIS Alkalosis elicits a compensatory response causing H+ ions to shift from cells to extracellular fluids This corrects the acid-base imbalance HCO3- HCO3- HCO3- HCO3- H+ H+ H+ HCO3- H+ H+ H+ HCO3- H+ H+

ALKALOSIS H+ ions are exchanged for K+ (potassium moves into cells) Thus serum concentrations of K+ are decreased And alkalosis causes hypokalemia HCO3- HCO3- HCO3- K+ K+ K+ HCO3- H+ K+ H+ K+ H+ K+ HCO3- H+ H+ H+ HCO3- K+ H+ H+ K+

ALKALOSIS Conversely when K+ ions are lost from the cellular and extracellular compartments Sodium and hydrogen ions enter cells in a ratio of 2:1 as replacement This loss of extracellular H+ causes alkalosis HCO3- HCO3- H+ H+ H+ HCO3- HCO3- Na+ Na+ H+ H+ Na+ HCO3- K+ K+ H+ Na+ HCO3- K+ K+ Na+ HCO3- Na+ K+ H+ K+ Na+ K+ K+

KIDNEY FUNCTION NORMAL Kidney function is altered by hypokalemia Na+ ions are reabsorbed into the blood when K+ ions are secreted into the urine by kidney tubules NORMAL Peritubular fluid Tubular lumen K+ Na+ K+ Na+ Na+ K+ Na+ K+ K+ Na+ Na+ Na+ K+ K+

KIDNEY FUNCTION HYPOKALEMIA Kidney function is altered by hypokalemia If adequate numbers of K+ are not available for this exchange H+ ions are secreted instead HYPOKALEMIA Peritubular fluid Tubular lumen H+ Na+ K+ Na+ Na+ K+ Na+ H+ H+ Na+ Na+ Na+ H+ K+

KIDNEY FUNCTION Hypokalemia promotes renal loss of H+ ions and thus results in alkalosis

NORMAL NEPHRON Normal nephron function is to secrete H+ and K+ in exchange for Na+ capillary distal tubule H+ K+ Na+ Blood Urine

NEPHRON ACTION IN HYPOKELEMIA In Hypokalemia the kidney selectively secretes H+ ions in preference to K+ ions The loss of H+ ions may lead to alkalosis H+ K+ Na+ distal tubule capillary Blood Urine

ALKALOSIS 3) the kidney then eliminates K+ ions which can lead to Hypokalemia 1) in alkalosis there is a decrease in extracellular fluid H+ H+ retained K+ K+ Na+ excreted distal tubule capillary Blood 2) the kidney retains hydrogen ions to correct the alkalosis Urine

CAUSES OF HYPOKALEMIA

TREATMENT OF HYPOKALEMIA Replacement of K+ either by: Oral K+ salt supplements Diet Intravenous administration of K+ salt solution Diuretic (spinolactone) if renal loss is at work

CALCIUM HOMEOSTASIS Ca++ plays an important role in: Muscle contraction Nerve impulse transmission Hormone secretion Blood clotting

Ca++ = 4.9 meq / liter CALCIUM HOMEOSTASIS Normal range for serum calcium is 9 - 10.5 mg/dl (4.5 - 5.3 meq / liter) The range for proper function has narrow limits Ca++ = 4.9 meq / liter

VITAMIN D Vitamin D is involved in maintaining serum Ca++ levels

VITAMIN D Source of vitamin D is either dietary or is synthesized by the body Cholesterol is converted in the skin by exposure to sunlight into a precursor product which is converted to an active form of vitamin D by the liver and kidneys

VITAMIN D Vitamin D enhances serum Ca++ levels by: 1) Directly promoting bone resorption with the release of chemical salts 2) Potentiating the effects of parathormone (PTH) on bone reabsorption 3) Increasing absorption of Ca++ ions from the intestine 4) Reabsorption by the kidney tubules

PARATHORMONE Secreted into the bloodstream by the parathyroid glands Essential part of the Ca++ homeostatic mechanisms

PARATHORMONE ACTION PTH 1) Increases calcium ion absorption from the intestine Enhances the synthesis of the active form of vitamin D 2) Favors reabsorption of calcium

PARATHORMONE ACTION PTH 3) Favors excretion of phosphate (PO4 -3) by kidney tubules 4) Enhances bone reabsorption with the release of Ca++

PARATHORMONE SECRETION PTH secretion is: Stimulated by decreased serum level of Ca++ Inhibited by increased serum levels of Ca++ Ca++ PTH Ca++ PTH

CALCITONIN Calcitonin is a hormone secreted by the thyroid gland Effects of calcitonin are weak compared to PTH

CALCITONIN Decreases serum Ca++ level by: 1) Interfering with bone resorption 2) Favoring bone uptake of calcium 3) Promoting excretion of calcium by the kidney CALCITONIN Calcitonin stimulates calcium salt deposit in bone Thyroid gland releases calcitonin Falling blood Ca++ levels Rising blood Ca++ levels Osteoclasts degrade bone and release Ca++ PTH Parathyroid glands release PTH

STORES OF CALCIUM bone calcium renal excretion extracellular calcium intracellular calcium absorption from intestine There are exchangeable stores of calcium in bone and in cells This total pool is in equilibrium with calcium in extracellular fluid Serum calcium levels are also maintained by a balance between renal excretion and intestinal absorption

Ca++ Ca++ = = 10.5 Hypercalcemia 9.0 Hypocalcemia HYPERCALCEMIA A serum calcium level of 10.5 mg / dl or above results in hypercalcemia Ca++ = 10.5 Hypercalcemia Ca++ = 9.0 Hypocalcemia

HYPERCALCEMIA High levels of Ca++: Interfere with nerve impulse Interfere with muscle contraction May cause kidney stones May precipitate out of body tissues (at high levels)

CAUSES FOR HYPERCALCEMIA 1) Overactive parathyroid glands 2) Hyperthyroidism increases bone resorption 3) Large doses of vitamin D

CAUSES FOR HYPERCALCEMIA 4) Confinement to bed for weeks at a time Bone reabsorption occurs at a more rapid rate than bone formation 5) Some malignancies secrete hormones that cause bone resorption

CAUSES FOR HYPERCALCEMIA 6) Milk-alkali syndrome Excessive and prolonged ingestion of milk and alkaline antacids (peptic ulcer) Sodium bicarbonate and calcium carbonate used as antacids Metabolic acidosis results because of increased levels of plasma bicarbonate

MILK-ALKALI SYNDROME Alkalosis promotes hypercalcemia 1) Causes increased kidney resorption of calcium 2) Decreases the capacity of bone to take up additional calcium

CAUSES OF HYPERCALCEMIA

TREATMENT Intravenous or oral administration of phosphate decreases plasma calcium levels by interfering with bone resorption Calcitonin reduces activities of bone destroying cells (osteoclasts) Glucocorticoids inhibit intestinal absorption of calcium

TREATMENT Some diuretics promote excretion of calcium by the kidneys Infusion of saline (NaCl) or sodium sulfate (Na2SO4) increases urinary calcium excretion

Ca++ Ca++ = = 9.0 Hypocalcemia 10.5 Hypercalcemia HYPOCALCEMIA Defined as a low serum calcium level Less than 9 mg / dl Ca++ = 9.0 Hypocalcemia Ca++ = 10.5 Hypercalcemia

HYPOCALCEMIA Physiological response to low calcium serum levels Increased secretion of PTH Which increases calcium by favoring bone resorption Intestinal absorption Renal reabsorption

CAUSES FOR HYPOCALCEMIA 1) Inadequate vitamin D a) Nutritional deficiencies b) Impaired intestinal absorption ex: partial gastrectomy c) Liver or kidney dysfunction interferes with formation of active form of vitamin D

CAUSES FOR HYPOCALCEMIA d) Inadequate exposure to sunlight Reduction in formation of active vitamin D in the skin e) Intestinal or bone unresponsiveness to action of vitamin D

CAUSES FOR HYPOCALCEMIA 2) Loss of parathyroid glands or loss of function 3) Pancreatitis Defect in PTH secretion Calcium deposits form in soft tissues

CAUSES FOR HYPOCALCEMIA 4) Renal failure Reduction in the formation of an active vitamin D metabolite Altered bone response to PTH is also a factor

CAUSES OF HYPOCALCEMIA

TREATMENT Calcium salts administered intravenously or orally Calcium gluconate or calcium chloride solutions Vitamin D may be given

END OF FLUID AND ELECTROLYTES PART 2