Human Anatomy & Physiology Fluid, Electrolyte, and Acid-Base Balance

10/26/2014

PowerPoint® Lecture Slides Body Water Content prepared by Human Anatomy Barbara& Physiology Heard, Atlantic Cape Community • Infants: 73% or more water (low body fat, College Ninth Edition low bone mass) • Adult males: ~60% water C H A P T E R 26 • Adult females: ~50% water (higher fat content, less skeletal muscle mass) – Adipose tissue least hydrated of all Fluid, Electrolyte, • Water content declines to ~45% in old age and Acid-Base Balance

Figure 26.1 The major fluid compartments of the body. Fluid Compartments Total body water Volume = 40 L

60% of body weight Plasma • Total body water = 40 L Volume = L, 320% ECFof • Two main fluid compartments

– Intracellular fluid (ICF) compartment: 2/3 in Interstitial Intracellular fluid (ICF) cells Volume = 25 L fluid (IF) Volume = 12 L 40% of body weight – Extracellular fluid (ECF) compartment: 1/3 80% of ECF outside cells • Plasma: 3 L • Interstitial fluid (IF): 12 L in spaces between cells – Usually considered part of IF: lymph, CSF, humors of the eye, synovial fluid, serous fluid, and gastrointestinal Extracellular secretions fluid (ECF) Volume = 15 L 20% of body weight

Electrolyte Concentration Electrolyte Concentration

• For single charged ions (e.g. Na+), 1 mEq = 1 mOsm • For bivalent ions (e.g. Ca2+), 1 mEq = 1/2 mOsm • 1 mEq of either provides same amount of charge

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Extracellular and Intracellular Fluids Extracellular and Intracellular Fluids

• Each fluid compartment has distinctive • ICF: pattern of electrolytes – Low Na+ and Cl– • ECF – Major cation: K+ 2– – All similar – Major anion HPO4 • Major cation: Na+ – More soluble proteins than in plasma • Major anion: Cl– – Except: higher protein, lower Cl– content of plasma

Figure 26.2 Electrolyte composition of blood plasma, interstitial fluid, and intracellular fluid. Figure 26.3 Exchange of gases, nutrients, water, and wastes between the three fluid compartments of the body. 160 Lungs Gastrointestinal Kidneys tract

140

120

Blood plasma Interstitial fluid 100 Blood O2 CO2 Nutrients H2O, H2O, Nitrogenous Intracellular fluid plasma Ions Ions wastes Na+ Sodium 80 K+ Potassium Ca2+ Calcium

Mg2+ Magnesium O2 CO2 Nutrients H2O Ions Nitrogenous 60 Interstitial – Bicarbonate wastes HCO3 fluid Cl– Chloride

2– solute concentration Total (mEq/L) HPO4 Hydrogen 40 phosphate 2– SO4 Sulfate

Water Balance and ECF Osmolality Figure 26.4 Major sources of water intake and output.

• Water intake must = water output = ~ 2500 100 ml Feces 4% Metabolism 10% 250 ml Sweat 8% ml/day 200 ml Insensible loss • Water intake: beverages, food, and Foods 30% 750 ml 700 ml via skin and metabolic water lungs 28% • Water output: urine (60%), insensible 2500 ml

water loss (lost through skin and lungs), Urine 60% perspiration, and feces Beverages 60% 1500 ml 1500 ml

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Figure 26.5 The thirst mechanism for regulating water intake.

Maintenance of Body fluid Osmolality ECF osmolality Plasma volume (5 –10%)

Blood pressure

Osmoreceptors Saliva Granular cells • Osmolality maintained at ~ 280 – 300 in hypothalamus in kidney

mOsm Renin-angiotensin- aldosterone Dry mouth mechanism

• Rise in osmolality  Angiotensin II – Stimulates thirst Hypothalamic – ADH release thirst center

Sensation of thirst; person takes a • Decrease in osmolality  drink

Water moistens – Thirst inhibition mouth, throat; stretches stomach, – ADH inhibition intestine

Water absorbed from GI tract

Initial stimulus

Regulation of Water Output: Influence of Figure 26.6 Mechanisms and consequences of ADH release. ECF osmolality Na+ concentration ADH in plasma

Plasma volume Stimulates • Other factors may trigger ADH release (5–10%), BP

Osmoreceptors Inhibits – Large changes in blood volume or pressure in hypothalamus Negative feedback inhibits • E.g.,  BP   ADH release due to blood vessel Baroreceptors in atria and Stimulates baroreceptors and renin-angiotensin-aldosterone large vessels mechanism Stimulates Posterior pituitary

• Factors lowering blood volume: intense sweating, Releases ADH

Antidiuretic vomiting, or diarrhea; severe blood loss; traumatic hormone (ADH) burns; and prolonged fever Targets

Collecting ducts of kidneys

Effects

Water reabsorption

Results in

ECF osmolality Scant urine Plasma volume

Disorders of Water Balance Disorders of Water Balance: Hypotonic Hydration • Principal abnormalities of water balance • Cellular overhydration, or water – Dehydration intoxication – Hypotonic hydration • Occurs with renal insufficiency or rapid – Edema excess water ingestion • ECF osmolality   hyponatremia  net osmosis into tissue cells  swelling of cells  severe metabolic disturbances (nausea, vomiting, muscular cramping, cerebral edema)  possible death • Treated with hypertonic saline

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Figure 26.7b Disturbances in water balance. Slide 1 Disorders of Water Balance: Edema

• Atypical accumulation of IF  tissue swelling Excessive 1 2 ECF osmotic 3 H2O moves (not cell swelling) H2O enters pressure falls into cells by the ECF osmosis; cells swell • Result of  fluid out of blood or  fluid into blood •  fluid out of blood caused by – Increased capillary hydrostatic pressure or permeability • Capillary hydrostatic pressure increased by incompetent venous valves, localized blood vessel blockage, congestive heart failure,  blood volume • Capillary permeability increased by ongoing inflammatory Consequences of hypotonic hydration (water gain). If more water than solutes is gained, cells swell. response

Edema Electrolyte Balance

•  fluid returning to blood result of • Electrolytes are salts, acids, bases, some – Imbalance in colloid osmotic pressures, e.g., proteins hypoproteinemia ( plasma protein levels  • Electrolyte balance usually refers only to low colloid osmotic pressure) salt balance • Fluids fail to return at venous ends of capillary beds • Salts control fluid movements; provide • Results from protein malnutrition, liver disease, or minerals for excitability, secretory activity, glomerulonephritis membrane permeability • Salts enter body by ingestion and metabolism; lost via perspiration, feces, urine, vomit

Central Role of Sodium Table 26.2 Sodium Concentration and Sodium Content

• Most abundant cation in ECF – Sodium salts in ECF contribute 280 mOsm of total 300 mOsm ECF solute concentration • Only cation exerting significant osmotic pressure – Controls ECF volume and water distribution – Changes in Na+ levels affects plasma volume, blood pressure, and ECF and IF volumes

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Regulation of Sodium Balance: Aldosterone Aldosterone

• Regardless of aldosterone presence • Aldosterone  decreased urinary output; – 65% Na+ reabsorbed in proximal tubules; 25% increased blood volume reclaimed in nephron loops – By active reabsorption of remaining Na+ in – Na + never secreted into filtrate distal convoluted tubule and collecting duct • Water in filtrate follows Na+ if ADH is • Also causes increased K+ secretion present –  Na+ in urine   water loss

Regulation of Sodium Balance: Aldosterone Regulation of Sodium Balance: Aldosterone

• Renin-angiotensin-aldosterone • Renin catalyzes production of mechanism main trigger for aldosterone angiotensin II release – Prompts aldosterone release from adrenal – Granular cells of JGC secrete renin in cortex response to –  Na+ reabsorption by kidney tubules • Sympathetic nervous system stimulation • Aldosterone release also triggered by •  filtrate NaCl concentration elevated K+ levels in ECF •  stretch (due to  blood pressure) of granular cells • Aldosterone brings about its effects slowly (hours to days)

Figure 26.8 Mechanisms and consequences of aldosterone release. Figure 26.9 Mechanisms and consequences of ANP release.

+ K+ concentration Body Na content Stretch of atria in the ECF triggers renin release, of heart due to BP increasing angiotensin II Releases

Negative Atrial natriuretic peptide feedback (ANP) Stimulates Targets

Adrenal cortex

Releases JG complex Hypothalamus and Adrenal cortex of the kidney posterior pituitary

Aldosterone Effects Effects

Targets Renin release* ADH release Aldosterone release Kidney tubules Angiotensin II Inhibits Inhibits

Collecting ducts Effects of kidneys Vasodilation Effects

+ + Na reabsorption K secretion Na+ and H2O reabsorption

Results in

Restores Blood volume

Results in Homeostatic plasma levels of Na+ and K+ Blood pressure

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Figure 26.10 Mechanisms regulating sodium and water balance help maintain blood pressure homeostasis. Influence of other Hormones Systemic blood pressure/volume

Filtrate NaCl Stretch in afferent concentration in ascending Inhibits baroreceptors arterioles limb of nephron loop in blood vessels • Female sex hormones (+) (+) (+)

Granular cells (+) Sympathetic – Estrogens:  NaCl reabsorption (like of kidneys nervous system Release (+) aldosterone) Renin Systemic arterioles Catalyzes conversion Causes

Angiotensinogen Angiotensin I Vasoconstriction (from liver) •  H2O retention during menstrual cycles and Results in Converting enzyme (in lungs) pregnancy Peripheral resistance (+) Angiotensin II Posterior pituitary (+) + (+) (+) Releases – Progesterone:  Na reabsorption (blocks Systemic arterioles Adrenal cortex ADH (antidiuretic hormone) Causes Secretes (+) aldosterone) Vasoconstriction Aldosterone Collecting ducts + Results in Targets of kidneys Causes • Promotes Na and H2O loss Peripheral resistance Distal kidney tubules Causes H2O reabsorption

+ Na+ (and H O) 2 • Glucocorticoids:  Na reabsorption and reabsorption Results in promote edema Blood volume (+) stimulates Renin-angiotensin-aldosterone Blood pressure Mechanism Neural regulation (sympathetic nervous system effects) ADH release and effects © 2013 Pearson Education, Inc. © 2013 Pearson Education, Inc.

Regulation of Potassium Balance Regulation of Potassium Balance

• Importance of potassium • Hyperkalemia - too much K+ – Affects RMP in neurons and muscle cells • Hypokalemia - too little K+ (especially cardiac muscle) • Both disrupt electrical conduction in heart •  ECF [K+]  RMP  depolarization  reduced excitability  •  ECF [K+]  hyperpolarization and – Sudden death nonresponsiveness

Regulation of Potassium Balance Influence of Plasma Potassium Concentration • K+ part of body's buffer system • Most important factor affecting K+ • H+ shifts in and out of cells in opposite secretion is its concentration in ECF direction of K+ to maintain cation balance, • High K+ diet   K+ content of ECF  K+ so entry into principal cells  K+ secretion – ECF K+ levels rise with acidosis • Low K+ diet or accelerated K+ loss reduces – ECF K+ levels fall with alkalosis its secretion • Interferes with activity of excitable cells

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Regulation of Potassium Balance Regulation of Calcium

• Influence of aldosterone • 99% of body's calcium in bones – Stimulates K+ secretion (and Na+ – Calcium phosphate salts reabsorption) by principal cells • Ca2+ in ECF important for + – Adrenal cortical cells directly sensitive to K – Blood clotting content of ECF – Cell membrane permeability • Increased K+ in adrenal cortex causes – Release of aldosterone  K+ secretion – Secretory activities • Abnormal aldosterone levels severely – Neuromuscular excitability - most important influence K+ levels

Regulation of Calcium Influence of PTH

• Hypocalcemia   excitability and • PTH promotes increase in calcium levels muscle tetany by targeting • Hypercalcemia  inhibits neurons and – Bones – osteoclasts break down matrix, muscle cells, may cause heart arrhythmias releasing calcium and phosphate to blood • Calcium balance controlled by parathyroid – Kidneys – increases calcium reabsorption; decreases phosphate ion reabsorption hormone (PTH) from parathyroid gland – Small intestine – increases calcium – Rarely deviates from normal limits absorption (indirectly through stimulation of kidney to activate vitamin D precursor)

Influence of PTH Figure 16.13 Effects of parathyroid hormone on bone, the kidneys, and the intestine. Hypocalcemia (low blood Ca2+)

PTH release from • 98% filtered calcium reabsorbed due to parathyroid gland PTH • If ECF calcium levels normal PTH secretion inhibited Osteoclast activity Ca2+ reabsorption Activation of in bone causes Ca2+ in kidney tubule vitamin D by kidney 3- and PO4 release • 75% of filtered phosphates reabsorbed in into blood PCT

– PTH inhibits this by decreasing the Tm Ca2+ absorption from food in small • Phosphate reabsorption also affected by intestine insulin (increases it) and glucagon

(decreases it) Ca2+ in blood

Initial stimulus Physiological response

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Regulation of Anions Acid-base Balance

• Cl– is major anion in ECF • pH affects all functional proteins and – Helps maintain osmotic pressure of blood biochemical reactions, so closely – 99% of Cl– is reabsorbed under normal pH regulated conditions • Normal pH of body fluids • When acidosis occurs, fewer chloride ions – Arterial blood: pH 7.4 are reabsorbed – Venous blood and IF fluid: pH 7.35 • Other anions have transport maximums – ICF: pH 7.0 and excesses are excreted in urine • Alkalosis or alkalemia: arterial pH >7.45 • Acidosis or acidemia: arterial pH <7.35

Acid-base Balance Acid-base Balance

• Most H+ produced by metabolism • Concentration of hydrogen ions regulated – Phosphorus-containing protein breakdown sequentially by releases phosphoric acid into ECF – Chemical buffer systems: rapid; first line of – Lactic acid from anaerobic respiration of defense glucose – Brain stem respiratory centers: act within 1–3 – Fatty acids and ketone bodies from fat min metabolism – Renal mechanisms: most potent, but require + – – H liberated when CO2 converted to HCO3 in hours to days to effect pH changes blood

Acid-base Balance: Chemical Buffer Figure 26.11 Dissociation of strong and weak acids in water. Systems • 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

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Chemical Buffer Systems Phosphate Buffer System

• Chemical buffer: system of one or more • Action nearly identical to bicarbonate compounds that act to resist pH changes buffer when strong acid or base is added • Components are sodium salts of: – Bind H+ if pH drops; release H+ if pH rises – – Dihydrogen phosphate (H2PO4 ), a weak acid 1. Bicarbonate buffer system 2– – Monohydrogen phosphate (HPO4 ), a weak 2. Phosphate buffer system base 3. Protein buffer system • Unimportant in buffering plasma • Effective buffer in urine and ICF, where phosphate concentrations are high

Respiratory Regulation of H+ Respiratory Regulation of H+

• Hypercapnia activates medullary • Alkalosis depresses respiratory center chemoreceptors – Respiratory rate and depth decrease –  Increased respiratory rate and depth – H+ concentration increases • Rising plasma H+ activates peripheral • Respiratory system impairment causes chemoreceptors acid-base imbalances –  Increased respiratory rate and depth – Hypoventilation  respiratory acidosis

– More CO2 is removed from the blood – Hyperventilation  respiratory alkalosis – H+ concentration is reduced

Renal Mechanisms of Acid-Base Balance Renal Mechanisms of Acid-base Balance

• Most important renal mechanisms • Renal regulation of acid-base balance – Conserving (reabsorbing) or generating new depends on kidney's ability to secrete H+ – HCO3 • H+ secretion occurs in PCT and collecting – – Excreting HCO3 duct type A intercalated cells: – + • Generating or reabsorbing one HCO3 – The H comes from H2CO3 produced in same as losing one H+ reactions catalyzed by carbonic anhydrase – inside cells • Excreting one HCO3 same as gaining one + + H+ – As H secreted, Na reabsorbed – See Steps 1 and 2 of following figure

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– + Figure 26.12 Reabsorption of filtered HCO3 is coupled to H secretion. Slide 1 Renal Mechanisms of Acid-base Balance 1 CO2 combines with water 2 H2CO3 is quickly split, forming within the tubule cell, forming + − H and bicarbonate ion (HCO3 ). H2CO3. 3a H+ is secreted Nucleus + Filtrate in into the filtrate. • Rate of H secretion changes with ECF tubule Peri- lumen PCT cell tubular 3b For each H+ secreted, CO levels capillary − 2 a HCO3 enters the ATPase peritubular capillary blood either via symport –  CO2 in peritubular capillary blood   rate with Na+ or via antiport + with CI−. of H secretion

3a 3b + 2 4 Secreted H + − – System responds to both rising and falling H 4 ATPase combines with HCO3 in the filtrate, forming concentrations * 5 CA 1 CA carbonic acid (H2CO3). − 6 HCO3 disappears from the filtrate at the same − rate that HCO3 (formed Tight within the tubule cell) junction enters the peritubular capillary blood. Primary active transport Transport protein 6 CO diffuses into the tubule 5 Secondary active transport 2 The H2CO3 formed in CA Carbonic anhydrase + Simple diffusion cell, where it triggers further H the filtrate dissociates to secretion. release CO2 and H2O.

– + 2– Figure 26.13 New HCO3 is generated via buffering of secreted H by HPO4 (monohydrogen phosphate). Slide 1 + 2 H2CO3 is quickly 3a Ammonium Ion Excretion 1 CO2 combines with water H is within the type A intercalated split, forming H+ and secreted into bicarbonate ion cell, forming H2CO3. the filtrate by a −) + (HCO3 . H ATPase pump. Nucleus Filtrate in tubule • More important mechanism for excreting Tight junction Peri- lumen tubular 3b For capillary each H+ acid secreted, a − HCO3 enters the peritubular • Involves metabolism of glutamine in PCT 1 capillary blood via an antiport cells carrier in a − − 2 HCO3 -CI + 3a 3b exchange process. • Each glutamine produces 2 NH4 and 2 ATPase (new) – 4 4 Secreted "new" HCO3 Type A H+ combines intercalated 2− with HPO4 – + cell of collecting duct in the tubular • HCO3 moves to blood and NH4 is 5 filtrate, out in urine Forming − excreted in urine H2PO4 . Primary active transport Transport protein 5 − Secondary active transport Ion channel The H2PO4 • Replenishes alkaline reserve of blood Simple diffusion Carbonic anhydrase is excreted Facilitated diffusion in the urine.

– + Figure 26.14 New HCO3 is generated via glutamine metabolism and NH4 secretion. Slide 1 + + Bicarbonate Ion Secretion 1 PCT cells 2a This weak acid NH4 2b For each NH4 secreted, − metabolize (ammonium) is secreted into a bicarbonate ion (HCO3 ) glutamine to the filtrate, taking the place of enters the peritubular capillary + − + + + NH4 and HCO3 . H on a Na -H antiport carrier. blood via a symport carrier. Filtrate in Nucleus tubule lumen • When body in alkalosis, type B Peri- PCT tubule cells tubular capillary intercalated cells

Glutamine Glutamine Glutamine – Deamination, – Secrete HCO3 1 oxidation, and + acidification – Reclaim H to acidify blood (+H+) 2a 2b

(new) 3

out in urine ATPase

Tight junction

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Bicarbonate Ion Secretion Respiratory Acidosis and Alkalosis

• Mechanism is opposite of bicarbonate ion • Most important indicator of adequacy of reabsorption process by type A respiratory function is P level (normally CO2 intercalated cells 35–45 mm Hg) – P above 45 mm Hg  respiratory acidosis • Even during alkalosis, nephrons and CO2 – • Common cause of acid-base imbalances collecting ducts conserve more HCO3 than they excrete • Due to decrease in ventilation or gas exchange • CO2 accumulates in blood • Characterized by falling blood pH and rising P CO2

Respiratory Acidosis and Alkalosis Metabolic Acidosis and Alkalosis

• P below 35 mm Hg  respiratory • Metabolic acidosis – low blood pH and CO2 – alkalosis HCO3 – Common result of hyperventilation often due – Causes to stress or pain • Ingestion of too much alcohol ( acetic acid) – • CO2 eliminated faster than produced • Excessive loss of HCO3 (e.g., persistent diarrhea) • Accumulation of lactic acid (exercise or shock), ketosis in diabetic crisis, starvation, and kidney failure

Metabolic Acidosis and Alkalosis Respiratory Compensation

• Metabolic alkalosis much less common • Changes in respiratory rate and depth than metabolic acidosis • In metabolic acidosis – – Indicated by rising blood pH and HCO3 – High H+ levels stimulate respiratory centers – Causes include vomiting of acid contents of – Rate and depth of breathing elevated stomach or by intake of excess base (e.g., – Blood pH is below 7.35 and HCO – level is antacids) 3 low

– As CO2 eliminated by respiratory system, P falls below normal CO2