Renal Physiology and Electrolyte Interactions

Electrostatic Interactions

• Small ions like Na+, Cl-, Mg2+, Mn2+, and K+ form electrostatic shields between similarly charged macro-ions, enabling larger associations.
• High concentrations of small ions can reduce the solvation of proteins in solution because water forms hydration shells around these ions.

Renal Regulation of Acid-Base Balance

• Kidneys adjust blood pH by controlling the excretion and reabsorption of bicarbonate (HCO3−).
• All serum bicarbonate is filtered through the glomerulus, where its reabsorption is equivalent to the removal of free hydrogen ions (H+).
• Renal responses to acid-base changes can occur over hours to days.

Sodium Bicarbonate Reabsorption

• HCO3− reabsorption primarily occurs in the proximal tubule and also in the collecting tubule.
• Carbonic anhydrase facilitates the breakdown of carbonic acid (H2CO3) in tubule cells, leading to the generation of HCO3− and H+.
• Na+/K+-ATPase pumps drive Na+ reabsorption, allowing intracellular HCO3− to diffuse into interstitial fluid.

Interstitial Fluid Buffers

• Buffers in interstitial fluid, including HCO3−, HPO42−, and NH3, enable the active secretion of H+.
• Equation at proximal convoluted tubules: H+ + HCO3− → H2O + CO2.
• Equation at distal tubules: H+ + HPO42− → H2PO4− indicates acid excretion.

Henderson-Hasselbalch Equation

• Used to relate pH, bicarbonate concentration, and carbon dioxide pressure:
  • pH = pKa + Log [HA]/[A−]
  • For bicarbonate buffering, pH = 6.1 + Log [HCO3−]/(0.03 × pCO2).

Bohr Effect

• The Bohr effect describes how changes in pH affect hemoglobin's affinity for oxygen (O2).
• As CO2 concentration increases in peripheral tissues, the resulting H+ ( \text{(from H2CO3)} ) competes with O2 for binding sites on hemoglobin, leading to O2 release into tissues.

CO2 Transport Mechanisms

• CO2 is more soluble in blood than O2; 5% is transported as dissolved CO2.
• 10% of CO2 binds to hemoglobin and plasma proteins, forming carbamino compounds.
• The majority (85%) is transported as bicarbonate (HCO3−) after conversion in red blood cells (RBCs).

Acid-Base Imbalance and Clinical Consequences

• Metabolic and pulmonary acidosis/alkalosis can result from inadequate buffering and may be fatal.
• Respiratory acidosis is characterized by high CO2 levels due to hypoventilation, causing symptoms like headache, dyspnea, and possible confusion.
• Respiratory alkalosis arises from excessive CO2 removal, with symptoms including lightheadedness and tingling of extremities.

Zwitterions and Isoelectric Points

• Zwitterions contain both acidic and basic functional groups, allowing them to accept and donate protons.
• The isoelectric point (pI) is where a molecule carries no net charge; calculations for pI rely on pKa values of acidic and basic groups.

Importance of Buffering

• Effective buffering maintains the stability of pH in biological systems, critical for enzyme function and cellular processes.
• Key buffer in blood includes carbonic acid (H2CO3) and bicarbonate (HCO3−), which operate in equilibrium to regulate pH.

Thermodynamics and Energy Changes

• Thermodynamics studies the relationship between heat and work in energy transfer.
• The First Law states that energy cannot be created or destroyed, only transformed.
• Enthalpy reflects heat content changes during reactions, and solvation affects the thermodynamics regarding protein structure and function.

Hydration Shells

• Hydration shells form around ions when dissolved in water, impacting the behavior of other ionic species in solution.
• The presence of hydration shells affects hydration dynamics and lowers the freezing point of saltwater compared to pure water.
• Proteins acquire a net charge in solution based on their ionizable R groups and the surrounding pH conditions.

Acid-Base Regulation

• pH Calculation: pH is derived from the concentration of hydrogen ions, represented as pH = -Log[H+].
• Henderson-Hasselbalch Equation: pH = pKa + Log[HCO3-]/(0.03 × pCO2); used to understand the relationship between pH, bicarbonate levels, and carbon dioxide pressure.

Bohr Effect

• Refers to the decrease in hemoglobin's affinity for oxygen (O2) in response to lower pH (higher H+ concentration).
• Results from the pressure difference of CO2 between tissues and circulation, facilitating CO2 diffusion from tissues to blood.

CO2 Transport Mechanisms

• Dissolved CO2: About 5% of CO2 is transported as dissolved gas in plasma.
• Bound to Hemoglobin: CO2 forms carbamino-haemoglobin with hemoglobin and plasma proteins; approx. 10% is transported this way.
• Bicarbonate Ions (HCO3-): Main method (about 85%) for CO2 transport; formed in red blood cells via the action of carbonic anhydrase.

Respiratory Conditions

• Acidosis: Lowered pH due to excess CO2; symptoms include headache, dyspnea, and possible causes include hypoventilation or lung diseases.
• Alkalosis: Increased pH from too little CO2; may result from hyperventilation or strong anxiety, symptoms include tingling and confusion.

Isoelectric Point & Zwitterions

• Isoelectric point (pI) is where a molecule has a net charge of zero; pI can determine a molecule's behavior in a given pH.
• Proteins and amino acids can exist in zwitterionic forms due to their capacity to act as both acids and bases.

Solvation & Hydration

• Solvation refers to the surrounding of solute molecules by solvent, affecting thermodynamic properties.
• Hydration shells form around ions in solution, changing the network of water molecules and influencing overall solubility.

Renal Regulation of Acid-Base Balance

• Kidneys manage pH through bicarbonate reabsorption and hydrogen ion secretion.
• Changes in renal function can alter acid-base status from hours to days.

Metabolic Disorders

• Metabolic Acidosis: Decreased bicarbonate leading to increased acidity; causes include renal failure and diabetic ketoacidosis.
• Metabolic Alkalosis: Increased bicarbonate due to excess loss of acid; common causes are severe vomiting and diuretic use.

Thermodynamics Principles

• Energy conservation is described by the First Law of Thermodynamics: energy cannot be created or destroyed, only transformed.
• Enthalpy (H): Reflects heat content in a system at constant pressure, calculated as ΔH = ΔE + PΔV.
• The Second Law highlights the inevitability of entropy increasing in isolated systems, illustrating that disorder increases over time.

Solution Chemistry

• Solutes increase entropy in solution; ionic solutes dissociate into cations and anions, impacting solvent organization.
• The overall entropy change in solutions is subtly negative due to the structured environment created around solutes compared to pure solvent.