Fluid, Electrolyte, and Acid-Base Balance Body Water Content • ________: 73% or more water (low body fat, low bone mass) • Adult males: ~_______% water • Adult females: ~50% water (higher fat content, less _______muscle mass) • Water content declines to ~_______% in old age Fluid Compartments • Total body water = 40 L 1. _______fluid (ICF) compartment: 2/3 or 25 L in cells 2. Extracellular fluid (ECF) compartment: 1/3 or 15 L • _______: 3 L • Interstitial fluid (IF): 12 L in spaces between cells • Other _______: lymph, CSF, humors of the eye, synovial fluid, serous fluid, and _______secretions

Composition of Body Fluids • Water: the _______solvent • Solutes: nonelectrolytes and electrolytes • _______: 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., _______salts, all acids and bases, and some proteins • The most abundant (most _______) solutes • Have greater osmotic power than _______, so may contribute to fluid shifts • Determine the _______and _______reactions of fluids

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

mEq/L = _______concentration (mg/L) _______weight of ion (mg/mmol)

 # of electrical charges on one ion

Electrolyte Concentration • For _______charged ions (e.g. Na+), 1 mEq = 1 mOsm • For _______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 _______: Na+ • Major _______: Cl–

Extracellular and Intracellular Fluids • ICF: • Low _______+ and _______– • Major cation: K+ • Major anion _______

Extracellular and Intracellular Fluids • _______, phospholipids, cholesterol, and neutral fats make up the bulk of dissolved solutes • 90% in _______ • 60% in _______ • 97% in _______

Fluid Movement Among Compartments • Regulated by _______and _______pressures • Water moves freely by _______; osmolalities of all body fluids are almost always equal • Two-way _______flow is substantial • Ion fluxes require _______transport or channels • Change in solute concentration of any compartment leads to net _______flow Water Balance and ECF Osmolality • Water _______= water output = _______ml/day • Water intake: beverages, food, and metabolic water • Water output: _______, insensible water _______ (skin and

lungs), perspiration, and feces Regulation of Water Intake • _______mechanism is the driving force for water intake • The hypothalamic thirst center osmoreceptors are stimulated by •  Plasma _______of 2–3% • Angiotensin II or baroreceptor input • Dry mouth • Substantial decrease in _______volume or pressure

Regulation of Water Intake • Drinking water creates inhibition of the thirst center • Inhibitory feedback signals include • Relief of _______mouth • Activation of stomach and _______stretch receptors

Regulation of Water Output • _______water losses • Insensible water loss: from lungs and skin • _______ • Minimum daily sensible water loss of 500 ml in urine to excrete wastes

• Body _______and _______ content are regulated in tandem by mechanisms that maintain cardiovascular function and blood pressure Regulation of Water Output: Influence of ADH • Water _______in collecting ducts is proportional to ADH release •  _______ dilute urine and  volume of body fluids •  ADH  concentrated _______ Regulation of Water Output: Influence of ADH • Hypothalamic _______trigger or inhibit ADH release • Other factors may trigger ADH release via large changes in blood volume or _______, e.g., fever, _______, vomiting, or diarrhea; blood loss; and traumatic burns Disorders of Water Balance: Dehydration • _______fluid balance

• _______water loss due to: hemorrhage, severe burns, prolonged vomiting or _______, profuse _______, water deprivation, diuretic abuse • Signs and symptoms: _______, dry flushed skin, oliguria • May lead to weight loss, fever, mental confusion, _______shock, and loss of electrolytes

Disorders of Water Balance: Hypotonic Hydration • Cellular _______, or water intoxication • Occurs with renal insufficiency or rapid excess water ingestion • ECF is _______ hyponatremia  net osmosis into tissue cells  swelling of cells  severe metabolic disturbances (nausea, vomiting, muscular _______, cerebral _______)  possible death Disorders of Water Balance: Edema • Atypical accumulation of _______fluid  tissue swelling • Due to anything that increases flow of fluid out of the _______or _______its return •  Blood pressure

•  Capillary permeability (usually due to inflammatory chemicals) • Incompetent venous _______, localized blood vessel blockage • Congestive heart failure, _______,  blood volume

Edema • Hindered fluid return occurs with an _______in colloid osmotic pressures, e.g., hypoproteinemia ( plasma proteins) • Fluids fail to return at the _______ends of capillary beds • Results from protein _______, liver disease, or glomerulonephritis

Edema • Blocked (or _______removed) lymph vessels • Cause leaked _______to accumulate in _______ •  Colloid osmotic pressure of IF draws fluid from the _______ • Results in _______blood pressure and severely impaired circulation

Electrolyte Balance

• Electrolytes are _______, acids, and _______ • Electrolyte balance usually refers only to salt balance • Salts enter the body by _______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 _______in the ECF • Sodium salts in the ECF contribute _______mOsm of the total 300 mOsm ECF solute concentration • Na+ leaks into _______and is pumped out against its _______gradient • Na+ content may change but ECF Na+ concentration remains stable due to osmosis Central Role of Sodium • Changes in _______sodium levels affect • Plasma volume, blood pressure • _______and _______volumes

• Renal acid-base control mechanisms are coupled to _______ion transport Regulation of Sodium Balance • No receptors are known that monitor Na+ levels in body fluids • Na+-water balance is linked to _______pressure and blood volume control mechanisms Regulation of Sodium Balance: Aldosterone • Na+ reabsorption • _______% is reabsorbed in the proximal tubules • _______% is reclaimed in the loops of Henle

• Aldosterone  active reabsorption of remaining Na+ • Water follows Na+ if _______is present

Regulation of Sodium Balance: Aldosterone • _______-_______mechanism is the main trigger for aldosterone release • Granular cells of JGA secrete renin in response to • Sympathetic nervous system stimulation •  Filtrate _______ •  Stretch (due to _______ blood pressure)

Regulation of Sodium Balance: Aldosterone • _______catalyzes the production of angiotensin II, which prompts aldosterone release from the adrenal cortex • Aldosterone release is also triggered by elevated _______ levels in the _______ • _______brings about its effects slowly (hours to days) Regulation of Sodium Balance: ANP • Released by _______cells in response to stretch ( blood pressure) • Effects • _______blood pressure and blood volume:

•  ADH, _______and _______production •  Excretion of Na+ and water • Promotes _______directly and also by decreasing production of angiotensin II

Influence of Other Hormones • Estrogens:  _______reabsorption (like aldosterone)

•  H2O retention during menstrual cycles and pregnancy

• _______:  Na+ reabsorption (blocks aldosterone) • Promotes Na+ and H2O loss

• _______:  Na+ reabsorption and promote edema Cardiovascular System Baroreceptors • _______alert the brain of increases in blood volume and pressure • • • •

_______nervous system impulses to the kidneys decline Afferent arterioles dilate _______increases Na+ and water output increase

Regulation of Potassium Balance • Importance of _______: • Affects RMP in neurons and muscle cells (especially cardiac muscle) •  _______ [K+]  _______ depolarization  reduced excitability •  ECF [K+] _______and _______

Regulation of Potassium Balance • _______+ shift in and out of cells • Leads to corresponding shifts in _______+ in the opposite direction to maintain cation balance • Interferes with activity of _______cells

Regulation of Potassium Balance • K_______balance is controlled in the cortical collecting ducts by changing the amount of potassium secreted into _______ • _______K+ content of ECF favors principal cell secretion of K+ • When K+ levels are _______, type A intercalated cells reabsorb some K+ left in the filtrate Regulation of Potassium Balance • Influence of _______ • Stimulates K+ secretion (and Na+ _______) by principal cells • Increased K+ in the adrenal cortex causes • Release of _______ • Potassium secretion

Regulation of Calcium • Ca2+ in _______is important for • • • •

Neuromuscular excitability Blood clotting Cell membrane permeability _______activities

Regulation of Calcium • _______  excitability and muscle tetany • _______ Inhibits neurons and muscle cells, may cause heart arrhythmias

• Calcium balance is controlled by parathyroid hormone (PTH) and _______ Influence of PTH • Bones are the largest reservoir for Ca2+ and phosphates • _______promotes increase in calcium levels by targeting bones, kidneys, and small intestine (indirectly through vitamin D) • Calcium _______and phosphate excretion go hand in hand Influence of PTH • Normally _______% of filtered phosphates are actively reabsorbed in the PCT • PTH inhibits this by _______the Tm Regulation of Anions • Cl– is the major _______in the ECF • Helps maintain the osmotic pressure of the blood • 99% of Cl– is _______under normal pH conditions

• When acidosis occurs, fewer chloride ions are reabsorbed • Other _______have transport maximums and excesses are excreted in urine Acid-Base Balance • _______affects all functional proteins and biochemical reactions • Normal pH of body fluids • _______blood: pH 7.4 • Venous blood and IF fluid: pH 7.35 • ICF: pH 7.0

• _______or alkalemia: arterial blood pH >7.45 • Acidosis or _______: 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 _______bodies from fat metabolism

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

Acid-Base Balance • Concentration of _______ions is regulated sequentially by • Chemical buffer systems: rapid; first line of defense • Brain stem _______centers: act within 1–3 min • Renal _______: most potent, but require hours to days to effect pH changes

Acid-Base Balance • Strong acids _______completely in water; can dramatically affect pH • _______acids dissociate partially in water; are efficient at preventing pH changes • Strong _______dissociate easily in water; quickly tie up H+ • Weak bases accept H+ more _______ Chemical Buffer Systems • Chemical _______: system of one or more compounds that act to resist pH changes when strong acid or base is added 1. _______buffer system 2. _______buffer system 3. _______buffer system

Bicarbonate Buffer System • Mixture of H2CO3 (_______acid) and salts of HCO3– (e.g., NaHCO3, a _______base) • Buffers _______and _______ • The only important ECF buffer Bicarbonate Buffer System • If _______acid is added:

• HCO3– ties up _______+ and forms H2CO3 • HCl + NaHCO3  H2CO3 + NaCl • pH _______only slightly, unless all available HCO3– (alkaline reserve) is used up • HCO3– concentration is closely regulated by the _______

Bicarbonate Buffer System • If _______base is added

• It causes H2CO3 to dissociate and _______H+ • H+ _______up the base (e.g. OH–) • NaOH + H2CO3  NaHCO3 + H2O • pH _______only slightly • H2CO3 supply is almost limitless (from CO2 released by respiration) and is subject to _______controls

Phosphate Buffer System • Action is nearly identical to the bicarbonate buffer • Components are sodium salts of: • _______phosphate (H2PO4–), a _______acid • _______phosphate (HPO42–), a _______base

• Effective buffer in urine and ICF, where phosphate concentrations are _______ Protein Buffer System • Intracellular _______are the most plentiful and powerful buffers; plasma proteins are also important • Protein molecules are _______ (can function as both a weak acid and a weak base) • When pH _______, organic acid or carboxyl (COOH) groups release H+ • When pH _______, NH2 groups bind H+

Physiological Buffer Systems • _______and _______systems • Act more slowly than chemical buffer systems • Have more capacity than chemical buffer systems

Respiratory Regulation of H+ • Respiratory system _______CO2 • A reversible equilibrium exists in the blood: • CO2 + H2O  H2CO3  H+ + HCO3–

• During CO2 _______the reaction shifts to the _______ (and H+ is incorporated into H2O) • During CO2 _______the reaction shifts to the _______ (and H+ is buffered by proteins) Respiratory Regulation of H+

• _______activates _______chemoreceptors • Rising plasma H+ activates _______chemoreceptors • More CO2 is removed from the blood • H+ concentration is _______

Respiratory Regulation of H+ • _______depresses the respiratory center • Respiratory rate and depth decrease • H+ concentration _______

• Respiratory system impairment causes acid-base imbalances • Hypoventilation  respiratory _______ • Hyperventilation  respiratory _______

Acid-Base Balance • Chemical buffers cannot eliminate excess _______or _______from the body • Lungs eliminate volatile _______acid by eliminating _______ • Kidneys eliminate other fixed _______acids (phosphoric, uric, and _______acids and _______) and prevent metabolic acidosis

Renal Mechanisms of Acid-Base Balance • Most important renal mechanisms

• Conserving (_______) or generating new HCO3– • _______HCO3–

• Generating or reabsorbing one HCO3– is the same as losing one _______ • Excreting one _______ is the same as gaining one _______ Renal Mechanisms of Acid-Base Balance • Renal regulation of acid-base balance depends on secretion of _______ • H+ secretion occurs in the PCT and in collecting duct type A _______cells: • The H+ comes from H2CO3 produced in reactions catalyzed by carbonic _______inside the cells • See Steps 1 and 2 of the following figure

Reabsorption of Bicarbonate • Tubule cell luminal membranes are _______to HCO3– • CO2 combines with water in PCT cells, forming H2CO3

• _______dissociates • H+ is secreted, and HCO3– is _______into capillary blood • Secreted H+ unites with HCO3– to form H2CO3 in filtrate, which generates _______and _______

• HCO3– _______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 _______ must be balanced by generating new _______ • Most filtered HCO3– is used up before filtrate reaches the _______ Excretion of Buffered H+ • Intercalated cells actively secrete _______ into urine, which is buffered by _______and _______ • Generated “new” HCO3– moves into the interstitial space via a cotransport system and then moves passively into peritubular capillary blood Ammonium Ion Excretion • Involves _______of glutamine in PCT cells • Each glutamine produces 2 _______ and 2 “new” _______ • HCO3– moves to the blood and NH4+ is excreted in urine Bicarbonate Ion Secretion • When the body is in _______, type B intercalated cells • Secrete HCO3– • Reclaim H+ and _______the blood

Bicarbonate Ion Secretion • Mechanism is the opposite of the _______ion reabsorption process by type A _______cells • Even during alkalosis, the _______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 _______level (normally 35–45 mm Hg) • PCO2 _______45 mm Hg  respiratory acidosis • Most common cause of acid-base imbalances • Due to _______in ventilation or gas exchange • Characterized by falling blood pH and rising P CO2

Respiratory Acidosis and Alkalosis • PCO2 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 _______blood CO2 levels • Indicated by abnormal HCO3– levels Metabolic Acidosis and Alkalosis • Causes of _______acidosis • Ingestion of too much _______ ( acetic acid) • Excessive loss of HCO3– (e.g., persistent diarrhea) • Accumulation of _______acid, shock, _______in diabetic crisis, starvation, and kidney failure

Metabolic Acidosis and Alkalosis • Metabolic alkalosis is much less common than metabolic acidosis

• Indicated by _______blood pH and HCO3– • Caused by _______of the acid contents of the stomach or by intake of excess base (e.g., antacids)

Effects of Acidosis and Alkalosis • Blood pH below _______ depression of CNS  _______ death • Blood pH above 7.8  excitation of nervous system  muscle _______, extreme _______, _______, 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 _______ • Kidneys attempt to correct respiratory _______imbalances

Respiratory Compensation • In metabolic _______ • • • •

High H+ levels stimulate the respiratory centers _______and _______of breathing are elevated Blood pH is below 7.35 and HCO3– level is _______ As CO2 is _______by the respiratory system, PCO2 falls below normal

Respiratory Compensation • Respiratory compensation for metabolic _______is revealed by: • _______, shallow breathing, allowing CO2 accumulation in the blood • High pH (over 7.45) and _______HCO3– levels

Renal Compensation • _______causes elevated PCO2 • (respiratory acidosis)

• _______compensation is indicated by _______HCO3– levels

• Respiratory _______exhibits low PCO2 and _______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