Body fluids

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)
– Adipose tissue least hydrated of all

• Water content declines to ~45% in old age

Fluid Compartments

• Total body water = 40 L

• Two main fluid compartments

– Intracellular fluid (ICF) compartment: 2/3 in cells

– Extracellular fluid (ECF) compartment: 1/3 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 secretions

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

Extracellular and Intracellular Fluids

• Each fluid compartment has distinctive pattern of electrolytes

• ECF

– All similar

• Major cation: Na+

• Major anion: Cl–

– Except: higher protein, lower Cl– content of plasma

• ICF:

– Low Na+ and Cl–

– Major cation: K+

– Major anion HPO42–

– More soluble proteins than in plasma

Water Balance and ECF Osmolality

• Water intake must = water output = ~ 2500 ml/day

• Water intake: beverages, food, and metabolic water

 • Water output: urine (60%), insensible water loss (lost through skin and lungs),
perspiration, and feces

Maintenance of Body fluid Osmolality

• Osmolality maintained at ~ 280 – 300 mOsm

• Rise in osmolality 

– Stimulates thirst

– ADH release

• Decrease in osmolality 

– Thirst inhibition

– ADH inhibition

Regulation of Water Output: Influence of ADH

• Other factors may trigger ADH release

– Large changes in blood volume or pressure

• E.g.,  BP   ADH release due to blood vessel baroreceptors and renin-

angiotensin-aldosterone mechanism

• Factors lowering blood volume: intense sweating, vomiting, or diarrhea;

severe blood loss; traumatic burns; and prolonged fever
Disorders of Water Balance

• Principal abnormalities of water balance

– Dehydration

– Hypotonic hydration

– Edema

Disorders of Water Balance: Hypotonic Hydration

• Cellular overhydration, or water intoxication

• Occurs with renal insufficiency or rapid 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

Disorders of Water Balance: Edema

• Atypical accumulation of IF  tissue swelling (not cell swelling)

• 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 response

Edema

•  fluid returning to blood result of

– Imbalance in colloid osmotic pressures, e.g., hypoproteinemia ( plasma protein

levels  low colloid osmotic pressure)

• Fluids fail to return at venous ends of capillary beds

• Results from protein malnutrition, liver disease, or glomerulonephritis

Electrolyte Balance

• Electrolytes are salts, acids, bases, some proteins

• Electrolyte balance usually refers only to salt balance

• Salts control fluid movements; provide minerals for excitability, secretory activity,
membrane permeability

• Salts enter body by ingestion and metabolism; lost via perspiration, feces, urine, vomit

Central Role of Sodium

• 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
Regulation of Sodium Balance: Aldosterone

• Regardless of aldosterone presence

– 65% Na+ reabsorbed in proximal tubules; 25% reclaimed in nephron loops

– Na + never secreted into filtrate

• Water in filtrate follows Na+ if ADH is present

–  Na+ in urine   water loss

Aldosterone

• Aldosterone  decreased urinary output; increased blood volume

– By active reabsorption of remaining Na+ in distal convoluted tubule and

collecting duct

• Also causes increased K+ secretion

Regulation of Sodium Balance: Aldosterone

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

– Granular cells of JGC secrete renin in response to

• Sympathetic nervous system stimulation

•  filtrate NaCl concentration

•  stretch (due to  blood pressure) of granular cells

• Renin catalyzes production of angiotensin II

– Prompts aldosterone release from adrenal cortex

 –  Na+ reabsorption by kidney tubules

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

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

Influence of other Hormones

• Female sex 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

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

• Hyperkalemia - too much K+

• Hypokalemia - too little K+

• Both disrupt electrical conduction in heart 

– Sudden death

• K+ part of body's buffer system

• H+ shifts in and out of cells in opposite direction of K+ to maintain cation balance, so

– ECF K+ levels rise with acidosis

– ECF K+ levels fall with alkalosis

• Interferes with activity of excitable cells

Influence of Plasma Potassium Concentration

• Most important factor affecting K+ secretion is its concentration in ECF

• High K+ diet   K+ content of ECF  K+ entry into principal cells  K+ secretion

• Low K+ diet or accelerated K+ loss reduces its secretion

Regulation of Potassium Balance

• Influence of aldosterone

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

– Adrenal cortical cells directly sensitive to K+ content of ECF

• Increased K+ in adrenal cortex causes

– Release of aldosterone  K+ secretion

• Abnormal aldosterone levels severely influence K+ levels

Regulation of Calcium

• 99% of body's calcium in bones

– Calcium phosphate salts

• Ca2+ in ECF important for

– Blood clotting

– Cell membrane permeability

– Secretory activities

– Neuromuscular excitability - most important

• Hypocalcemia   excitability and muscle tetany

• Hypercalcemia  inhibits neurons and muscle cells, may cause heart arrhythmias

• Calcium balance controlled by parathyroid hormone (PTH) from parathyroid gland

– Rarely deviates from normal limits

Influence of PTH
 • PTH promotes increase in calcium levels by targeting

– Bones – osteoclasts break down matrix, releasing calcium and phosphate to

blood

– Kidneys – increases calcium reabsorption; decreases phosphate ion reabsorption

– Small intestine – increases calcium absorption (indirectly through stimulation of

kidney to activate vitamin D precursor)

• 98% filtered calcium reabsorbed due to PTH

• If ECF calcium levels normal PTH secretion inhibited

• 75% of filtered phosphates reabsorbed in PCT

– PTH inhibits this by decreasing the Tm

• Phosphate reabsorption also affected by insulin (increases it) and glucagon (decreases
it)

Regulation of Anions

• Cl– is major anion in ECF

– Helps maintain osmotic pressure of 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, so closely regulated

• 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 pH >7.45

 • Acidosis or acidemia: arterial pH <7.35

• Most H+ produced by metabolism

– Phosphorus-containing protein breakdown releases phosphoric acid into ECF

– Lactic acid from anaerobic respiration of glucose

– Fatty acids and ketone bodies from fat metabolism

– H+ liberated when CO2 converted to HCO3– in blood

• Concentration of hydrogen ions 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: Chemical Buffer 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

Chemical Buffer Systems

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

– Bind H+ if pH drops; release H+ if pH rises

– Bicarbonate buffer system

– Phosphate buffer system

– Protein buffer system

Phosphate Buffer System

• Action nearly identical to bicarbonate buffer

• Components are sodium salts of:

– Dihydrogen phosphate (H2PO4–), a weak acid

– Monohydrogen phosphate (HPO42–), a weak base

• Unimportant in buffering plasma

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

Respiratory Regulation of H+

• Hypercapnia activates medullary chemoreceptors

–  Increased respiratory rate and depth

• Rising plasma H+ activates peripheral chemoreceptors

–  Increased respiratory rate and depth

– More CO2 is removed from the blood

– H+ concentration is reduced

• Alkalosis depresses respiratory center

– Respiratory rate and depth decrease

– H+ concentration increases

• Respiratory system impairment causes acid-base imbalances

 – Hypoventilation  respiratory acidosis

– Hyperventilation  respiratory alkalosis

Renal Mechanisms of Acid-Base Balance

• Most important renal mechanisms

– Conserving (reabsorbing) or generating new HCO3–

– Excreting HCO3–

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

• Excreting one HCO3– same as gaining one H+

• Renal regulation of acid-base balance depends on kidney's ability to secrete H +

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

– The H+ comes from H2CO3 produced in reactions catalyzed by carbonic anhydrase

inside cells

– As H+ secreted, Na+ reabsorbed

– See Steps 1 and 2 of following figure

• Rate of H+ secretion changes with ECF CO2 levels

 –  CO2 in peritubular capillary blood   rate of H+ secretion

– System responds to both rising and falling H+ concentrations

Ammonium Ion Excretion

• More important mechanism for excreting acid

• Involves metabolism of glutamine in PCT cells

• Each glutamine produces 2 NH4+ and 2 "new" HCO3–

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

• Replenishes alkaline reserve of blood

Bicarbonate Ion Secretion

• When body in alkalosis, type B intercalated cells

– Secrete HCO3–

– Reclaim H+ to acidify blood

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

cells

• Even during alkalosis, nephrons and collecting ducts conserve more HCO3– than they
excrete

Respiratory Acidosis and Alkalosis

• Most important indicator of adequacy of respiratory function is PCO2 level (normally 35–
45 mm Hg)

– PCO2 above 45 mm Hg  respiratory acidosis

• Common cause of acid-base imbalances

• Due to decrease in ventilation or gas exchange

• CO2 accumulates in blood

 • Characterized by falling blood pH and rising PCO2

• PCO2 below 35 mm Hg  respiratory alkalosis

– Common result of hyperventilation often due to stress or pain

• CO2 eliminated faster than produced

Metabolic Acidosis and Alkalosis

• Metabolic acidosis – low blood pH and HCO3–

– Causes

• Ingestion of too much alcohol ( acetic acid)

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

• Accumulation of lactic acid (exercise or shock), ketosis in diabetic crisis,

starvation, and kidney failure

• Metabolic alkalosis much less common than metabolic acidosis

– Indicated by rising blood pH and HCO3–

– Causes include vomiting of acid contents of stomach or by intake of excess base

(e.g., antacids)

Respiratory Compensation

• Changes in respiratory rate and depth

• In metabolic acidosis

– High H+ levels stimulate respiratory centers

– Rate and depth of breathing elevated

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

– As CO2 eliminated by respiratory system, PCO2 falls below normal