Chp.26

• Factors Determining Body Water Content:

  • Sex: Healthy young males have a greater percentage of body water content compared to healthy young females (who typically have more body fat and less skeletal muscle).

  • Age: Healthy infants have the highest percentage of body water content, while healthy older adults have the lowest.

  • Tissue Type: Skeletal muscle has a significantly higher water content compared to adipose (fat) tissue, which is the least hydrated body tissue.

• Fluid Compartments and Volumes:

  • Total Body Water: Approximately $40\,L$ in a healthy adult, accounting for $60\%$ of total body weight.

  • Intracellular Fluid (ICF):

    • The fluid located within cells.

    • Volume: $25\,L$.

    • Percentage: $40\%$ of total body weight ($2/3$ of total body water).

  • Extracellular Fluid (ECF):

    • The fluid located outside of cells.

    • Volume: $15\,L$.

    • Percentage: $20\%$ of total body weight ($1/3$ of total body water).

    • Sub-compartments of ECF:

      • Interstitial Fluid (IF): The fluid in the microscopic spaces between tissue cells. Volume is $12\,L$.

      • Plasma: The fluid portion of blood. Volume is $3\,L$.

Solute Composition of Body Fluids

• Extracellular Fluids (ECF):

  • Major Cation: Sodium ($Na^+$).

  • Major Anion: Chloride ($Cl^-$).

  • Secondary Anion: Bicarbonate ($HCO_3^-$).

• Intracellular Fluid (ICF):

  • Major Cation: Potassium ($K^+$).

  • Major Anion: Hydrogen phosphate ($HPO_4^{2-}$).

  • Other Significant Solutes: Magnesium ($Mg^{2+}$) and Protein anions.

• Electrolytes vs. Nonelectrolytes:

  • Electrolytes:

    • Include salts, acids, and bases.

    • Each molecule dissociates into at least two ions.

    • Have greater osmotic power than nonelectrolytes at equal concentrations because each particle contributes to the total number of solutes.

    • Are the most numerous solutes in body fluids.

    • Have the greatest ability to cause fluid shifts.

  • Nonelectrolytes:

    • Examples include glucose, lipids, and urea.

    • Have chemical bonds (usually covalent) that prevent dissociation in solution.

• Concentration Calculations:

  • The formula for milliequivalents per liter ($mEq/L$) is:

    • $\text{mEq/L} = \frac{\text{ion concentration (mg/L)}}{\text{atomic weight of ion (mg/mmol)}} \times \text{no. of electrical charges on one ion}$

  • Sodium Calculation (Example):

    • Given: concentration = $3270\,mg/L$, atomic weight = $23\,mg/mmol$, charge = $1$.

    • $\frac{3270}{23} \times 1 \approx 142.17\,mEq/L$.

  • Magnesium Calculation (Example):

    • Given: concentration = $40\,mg/L$, atomic weight = $24\,mg/mmol$, charge = $2$.

    • $\frac{40}{24} \times 2 \approx 3.33\,mEq/L$.

Fluid Shifts and Water Regulation

• Mechanisms of Fluid Exchange:

  • Exchanges between plasma and Interstitial Fluid (IF) occur across capillary walls.

  • The hydrostatic pressure of blood (osmotic pressure) forces nearly protein-free plasma out of the blood into the interstitial space.

  • Exchanges between the Interstitial Fluid (IF) and Intracellular Fluid (ICF) occur across plasma membranes.

  • Plasma serves as the "highway" for delivering substances throughout the body.

  • Anything that changes the solute concentration in any compartment leads to net water flows.

  • The osmolalities of all body fluids are typically equal because water moves freely between compartments to reach equilibrium.

  • Osmotic Effect: An increase in the solute content of the Extracellular Fluid (ECF) leads to a shift of water out of the cells via osmosis.

• Water Intake Sources:

  1. Beverages (Greatest proportion).

  2. Foods.

  3. Metabolic water (water of oxidation produced during cellular metabolism).

• Water Output Sources:

  1. Urine (Greatest proportion).

  2. Insensible water loss (water vaporizing out of the lungs in expired air and diffusing through the skin).

  3. Sweat.

  4. Feces.

Feedback Mechanisms for Water Balance

• Thirst Mechanism:

  • Activated by the hypothalamic thirst center.

  • Stimuli for Thirst:

    1. Increased plasma osmolality.

    2. Dry mouth.

    3. Decreased blood volume or blood pressure.

  • Sensation Quenching: Thirst is quenched when the mucosa of the mouth/throat is moistened or when the stomach/small intestine is distended. This provides negative feedback before the water is actually absorbed, preventing over-ingestion.

• Hormonal Control (Antidiuretic Hormone - ADH):

  • Hypothalamic osmoreceptors detect an increase in ECF osmolality and stimulate the release of ADH from the posterior pituitary.

  • Low ADH Levels: Result in less water reabsorption in the collecting ducts, leading to a larger volume of dilute urine.

  • High ADH Levels: Result in more water reabsorption in the collecting ducts, leading to a smaller volume of concentrated urine.

  • ADH secretion is also stimulated by large changes in blood volume or pressure.

• Obligatory Water Loss:

  • Refers to the unavoidable output of water that must occur to clear the body of waste products.

  • Includes insensible water loss from lungs/skin and the minimum volume of urine needed to excrete solutes (approximately $500\,mL$ per day).

Disorders of Water Balance

• Dehydration: Occurs when water loss exceeds water intake over time. It leads to a decrease in blood volume and falling blood pressure. Possible causes include profuse sweating or hemorrhage.

• Hypotonic Hydration: Also known as water intoxication. Body fluids become excessively diluted and excess water enters tissue cells, causing them to swell. It may result from renal insufficiency or rapid intake of excessive amounts of water. This can lead to cerebral edema, coma, and death.

• Edema: An atypical accumulation of fluid specifically in the interstitial space, leading to tissue swelling. It impairs tissue function by increasing the distance nutrients and oxygen must diffuse between the blood and cells. It can result from any event that increases the flow of fluid out of blood or hinders its return (e.g., high blood pressure, low plasma protein).

Electrolyte Regulation

• Sodium (Na+):

  • The most important and abundant cation in the ECF.

  • Concentration in ECF largely determines the osmolality of ECF fluids and influences the excitability of neurons and muscles.

  • Total body amount of $Na^+$ determines the ECF volume and therefore blood pressure.

  • Aldosterone: Released by the adrenal cortex in response to decreased body $Na^+$ or increased body $K^+$ levels. Its effects are increased reabsorption of $Na^+$ and increased secretion of $K^+$, which increases ECF volume.

  • Renin-Angiotensin-Aldosterone System (RAAS): The body's main mechanism for increasing (not decreasing) blood volume and blood pressure.

  • Atrial Natriuretic Peptide (ANP): Decreases blood pressure and volume by inhibiting vasoconstriction and sodium/water retention.

  • Estrogens: Enhance reabsorption of salt by renal tubules (explaining water retention during menstrual cycles).

  • Progesterone: Decreases $Na^+$ reabsorption by blocking aldosterone's action.

  • Cardiovascular Baroreceptors: Detect rising arterial blood pressure, leading to vasodilation and enhanced $Na^+$ and water loss in urine.

• Potassium (K+):

  • Regulated by the kidneys: The proximal convoluted tubule (PCT) and nephron loop reabsorb about $90\%$ of filtered $K^+$.

  • The distal convoluted tubule (DCT) and collecting ducts secrete variable amounts of $K^+$ to maintain balance.

  • Aldosterone enhances $K^+$ secretion.

  • Hyperkalemia: Excessive blood potassium; can lead to sudden cardiac arrest.

• Calcium (Ca2+):

  • Parathyroid Hormone (PTH): The most important regulator of blood calcium.

    • Bones: Activates osteoclasts to break down bone matrix and release calcium.

    • Kidneys: Increases calcium reabsorption in renal tubules.

    • Small Intestine: Increases calcium absorption from food.

  • Hypocalcemia: Low blood calcium; can lead to tetany (muscle spasms).

  • Hypercalcemia: High blood calcium; inhibits neurons and muscle cells and can cause heart arrhythmias.

• Anions:

  • Chloride (Cl-): The ion that usually accompanies $Na^+$ reabsorption under normal circumstances.

Acid-Base Balance

• Sources of Acids:

  • Fat metabolism (produces fatty acids and ketone bodies).

  • Anaerobic respiration of glucose (produces lactic acid).

  • Protein breakdown (produces phosphoric acid).

  • Carbon dioxide loading in the blood (produces carbonic acid).

• Definitions:

  • Strong Acids: Dissociate completely in water and release many $H^+$ ions.

  • Weak Acids: Dissociate only partially in water.

  • Alkalosis: Arterial blood pH rises above $7.45$.

  • Physiological Acidosis: Arterial blood pH drops below $7.35$.

• Chemical Buffer Systems:

  • Act within a fraction of a second to resist pH changes.

  • Bicarbonate Buffer System: The main buffer of the Extracellular Fluid (ECF). Consists of a mixture of carbonic acid ($H_2CO_3$) and sodium bicarbonate ($NaHCO_3$).

  • Phosphate Buffer System: Very effective in urine and in the Intracellular Fluid (ICF). Consists of salts of dihydrogen phosphate ($H_2PO_4^-$) and monohydrogen phosphate ($HPO_4^{2-}$).

  • Protein Buffer System: The most important buffer in the ICF. Involves amino acid side chains (like carboxyl groups or amino groups) that act as weak acids or weak bases.

• Respiratory Regulation:

  • Follows the equation: $CO_2 + H_2O \rightleftharpoons H_2CO_3 \rightleftharpoons H^+ + HCO_3^-$.

  • When plasma $H^+$ rises, the equation shifts back to the left to utilize bicarbonate and produce $CO_2$ for exhalation.

  • Alkalosis Effect: An increase in blood pH (alkalosis) results in a decrease in ventilation (slower, shallower breathing) to retain $CO_2$.

  • Hyperventilation: Leads to the net elimination of carbon dioxide, which causes alkalosis.

Renal Regulation and Abnormalities

• Renal Mechanisms:

  • Kidneys are the ultimate long-term acid-base regulators because they can rid the body of nonvolatile (fixed) acids (like lactic or phosphoric acid) and renew chemical buffer components.

  • Reabsorption of filtered $HCO_3^-$ is dependent on $H^+$ secretion.

  • Acidosis Response: Type A intercalated cells in the collecting ducts secrete $H^+$ and reclaim $HCO_3^-$ and $K^+$.

  • Alkalosis Response: Type B intercalated cells in the collecting ducts secrete $HCO_3^-$ and reclaim $H^+$ (less common).

  • Most important urine buffer is the phosphate buffer (secreting $H^+$ combined with $HPO_4^{2-}$).

  • New $HCO_3^-$ can also be generated via glutamine metabolism in the PCT, which produces ammonium ($NH_4^+$) for secretion.

• Classifying Imbalances:

  • Respiratory Acidosis: Characterized by falling blood pH and rising $P_{CO_2}$. Often caused by pneumonia, cystic fibrosis, or shallow breathing. Common cause of acid-base imbalance.

  • Respiratory Alkalosis: Caused by eliminating $CO_2$ faster than it is produced (hyperventilation).

  • Metabolic Acidosis: Low blood pH and low $HCO_3^-$ levels. Causes include severe diarrhea or untreated diabetes.

  • Metabolic Alkalosis: Rising blood pH and rising $HCO_3^-$ levels. Typical causes include vomiting the acidic contents of the stomach or over-ingesting antacids.

• Blood Value Analysis (Case Study):

  • Values: $pH = 7.32$ (Acidic), $P_{CO_2} = 60\,mm\,Hg$ (High, suggests respiratory cause), $HCO_3^- = 29\,mEq/L$ (High, suggests renal compensation is occurring).

  • Conclusion: This is respiratory acidosis being compensated by renal mechanisms.

• pH Limits:

  • Blood pH below $6.8$ leads to central nervous system depression and coma.

  • Blood pH above $7.8$ leads to tetany and hyperexcitability.