Introduction: An Exhaustive Review of Chemical Principles
Welcome to Session 21. This module is an exhaustive, high-intensity review of the fundamental and applied chemical concepts essential for medicine. We will delve far beyond simple definitions to rigorously explore the specific terminology, quantitative relationships, and intricate biological applications that form the basis of challenging IMAT questions. The objective is to construct an unshakeable foundation of knowledge, leaving no conceptual stone unturned.
Part 1: Stoichiometry, Solutions, and Thermodynamics
This section provides a deep dive into the quantitative principles governing chemical reactions, mixtures, and energy, with a relentless focus on their physiological relevance.
1.1 Core Concepts: Concentration, Gases, and Solutions
- Units of Concentration: A precise understanding is mandatory.
- Molarity (M): Moles of solute per liter of solution (mol/L). Temperature-dependent.
- Molality (m): Moles of solute per kilogram of solvent (mol/kg). Temperature-independent, preferred for colligative properties.
- Normality (N): Equivalents of solute per liter of solution (eq/L). An 'equivalent' is a mole of the reactive species (e.g., H⁺ for acids). Simplifies titration calculations (N₁V₁ = N₂V₂).
- Gas Laws in Physiology:
- Dalton's Law: The partial pressure gradient (e.g., alveolar PO₂ ≈ 104 mmHg vs. venous blood PO₂ ≈ 40 mmHg) is the driving force for gas exchange.
- Henry's Law: The concentration of a dissolved gas is proportional to its partial pressure (C = k * P_gas). Explains decompression sickness.
- Osmolarity and Tonicity:
- Osmolarity: The total moles of all solute particles per liter of solution (osmol/L), calculated by Π = iMRT.
- Tonicity: Describes the effect a solution will have on cell volume, depending on impermeable solutes.
- Colloid Osmotic Pressure (Oncotic Pressure): Exerted by albumin in blood plasma, this pressure retains fluid within capillaries, counteracting hydrostatic pressure. Low albumin causes edema.
- Solubility Product (Ksp): For a salt like Ca₃(PO₄)₂, Ksp = [Ca²⁺]³[PO₄³⁻]². The common ion effect decreases solubility when a common ion is present.
Effect of Osmotic Pressure on Red Blood Cells
1.2 Chemical Kinetics: The Rate of Reaction
- Reaction Rate & Rate Law: The rate of a reaction is influenced by concentration, temperature, and catalysts. The rate law expresses this relationship: for a reaction aA + bB → cC, Rate = k[A]ˣ[B]ʸ. The exponents x and y are the reaction orders and must be determined experimentally.
- Reaction Orders:
- Zero-Order: Rate = k. The rate is independent of reactant concentration. Alcohol metabolism is an example.
- First-Order: Rate = k[A]. The rate is directly proportional to the concentration of one reactant. Radioactive decay follows this.
- Second-Order: Rate = k[A]² or Rate = k[A][B]. The rate is proportional to the square of a reactant's concentration or the product of two concentrations.
- Activation Energy (Ea) & Catalysts: The Arrhenius equation relates the rate constant (k) to temperature and activation energy. Catalysts (like enzymes) increase the reaction rate by providing an alternative reaction pathway with a lower activation energy, without being consumed in the process.
Reaction Energy Profile
1.3 Thermodynamics and Equilibrium
💡 Advanced Insights
The spontaneity of a process is determined by Gibbs Free Energy: ΔG = ΔH - TΔS.
- Gibbs Free Energy & Equilibrium: At equilibrium, ΔG = 0. The relationship between the standard free energy change (ΔG°) and the equilibrium constant (Keq) is ΔG° = -RTln(Keq).
- Le Chatelier's Principle: If a change of condition is applied to a system in equilibrium, the system will shift in a direction that relieves the stress. This is fundamental to physiological regulation, such as the binding of O₂ to hemoglobin. High altitude (low O₂) shifts the equilibrium to the right, favoring O₂ release.
- Electrochemistry & ETC: Electron flow is spontaneous from a lower standard reduction potential (E°) to a higher E°. The relationship is ΔG° = -nFE°. For the process to be spontaneous, ΔE° must be positive, making ΔG° negative.
- Energetic Coupling: The cell drives an endergonic reaction by coupling it to the highly exergonic hydrolysis of ATP, making the overall ΔG negative.
Part 2: Acids, Bases, and Buffers
This section provides an exhaustive analysis of pH, a parameter under the tightest physiological control.
2.1 Core Concepts: From Theory to Physiology
- Acid-Base Theories: Including Arrhenius (H⁺/OH⁻ producer), Brønsted-Lowry (H⁺ donor/acceptor), and Lewis (e⁻ pair acceptor/donor).
- Henderson-Hasselbalch Equation: pH = pKa + log([A⁻]/[HA]). This equation is the quantitative basis of buffers. A buffer has its maximum capacity when pH = pKa.
- Biological Buffers & Hemoglobin: Key systems include the bicarbonate buffer (extracellular), phosphate buffer (intracellular), and proteins. Hemoglobin's buffering capacity is linked to the Bohr effect (H⁺/CO₂ reduce O₂ affinity) and the Haldane effect (deoxygenation promotes H⁺ binding and CO₂ transport).
- Isoelectric Point (pI): The pH at which a molecule has a net charge of zero. For acidic amino acids, it's the average of the two lowest pKa values. For basic amino acids, it's the average of the two highest pKa values.
Titration Curve of Phosphoric Acid (H₃PO₄)
2.2 Clinical Application: Acid-Base Balance & Anion Gap
💡 Advanced Insights: Acid-Base Disorders
The equation CO₂ + H₂O ⇌ H₂CO₃ ⇌ H⁺ + HCO₃⁻ is central. The Anion Gap = [Na⁺] - ([Cl⁻] + [HCO₃⁻]) helps differentiate causes of metabolic acidosis. A high anion gap (HAGMA) suggests addition of an acid (MUDPILES: Methanol, Uremia, DKA, Propylene glycol, Isoniazid, Lactic acidosis, Ethylene glycol, Salicylates). A normal gap (NAGMA) suggests loss of bicarbonate (HARDUP: Hyperalimentation, Acetazolamide, Renal tubular acidosis, Diarrhea, Uretero-enteric fistula, Pancreatic fistula).
| Disorder | Primary Change | Cause Example | Compensation | Anion Gap |
|---|---|---|---|---|
| Respiratory Acidosis | ↑ pCO₂ → ↓ pH | Hypoventilation | Kidneys retain HCO₃⁻ | Normal |
| Respiratory Alkalosis | ↓ pCO₂ → ↑ pH | Hyperventilation | Kidneys excrete HCO₃⁻ | Normal |
| Metabolic Acidosis | ↓ HCO₃⁻ → ↓ pH | Ketoacidosis, Diarrhea | Hyperventilation (↓ pCO₂) | High or Normal |
| Metabolic Alkalosis | ↑ HCO₃⁻ → ↑ pH | Vomiting, Diuretics | Hypoventilation (↑ pCO₂) | Normal |
Part 3: Applied Biomolecules and Structure
This section explores biomolecular structure-function relationships at a level required for medical science.
3.1 Proteins: The Workhorses of the Cell
- Primary (1°) Structure: The amino acid sequence linked by peptide bonds.
- Secondary (2°) Structure: Local folding (α-Helix, β-Sheet) stabilized by backbone H-bonds.
- Tertiary (3°) Structure: Overall 3D shape stabilized by R-group interactions (hydrophobic interactions, disulfide bonds, etc.).
- Quaternary (4°) Structure: Assembly of multiple polypeptide subunits.
3.2 Carbohydrates: Energy and Structure
- Monosaccharides: Simple sugars like glucose, fructose, and galactose. They can exist as epimers (differ at one chiral center) and anomers (α vs β, differ at the anomeric carbon).
- Disaccharides: Two monosaccharides joined by a glycosidic linkage. Sucrose (glucose-α-1,2-fructose), Lactose (galactose-β-1,4-glucose), Maltose (glucose-α-1,4-glucose).
- Polysaccharides: Polymers of monosaccharides. Starch (plant energy storage, α-linkages), Glycogen (animal energy storage, branched α-linkages), Cellulose (plant structure, β-linkages, indigestible by humans).
3.3 Lipids: Membranes, Energy, and Signaling
- Fatty Acids: Saturated (no double bonds) vs. Unsaturated (one or more double bonds).
- Triacylglycerols: Three fatty acids esterified to a glycerol backbone. Main form of energy storage.
- Phospholipids: Form the lipid bilayer of cell membranes. Amphipathic nature is key.
- Steroids: Four-ring structure. Cholesterol acts as a membrane fluidity buffer and is the precursor to steroid hormones.
- Lipoproteins: Transport lipids in blood (Chylomicrons, VLDL, LDL, HDL).
3.4 Nucleic Acids: The Basis of Heredity
- Nucleotides: The building blocks, composed of a nitrogenous base, a pentose sugar (deoxyribose in DNA, ribose in RNA), and 1-3 phosphate groups.
- Nitrogenous Bases: Purines (Adenine, Guanine - two rings) and Pyrimidines (Cytosine, Thymine (DNA), Uracil (RNA) - one ring).
- DNA Structure: A double helix of two antiparallel strands. Bases are paired via hydrogen bonds: A with T (2 H-bonds) and G with C (3 H-bonds). The backbone consists of alternating sugar and phosphate groups linked by phosphodiester bonds.
DNA Double Helix Structure
3.5 Enzyme Kinetics and Inhibition
💡 Advanced Insights: Enzyme Regulation
The Michaelis-Menten equation, V = (Vmax * [S]) / (Km + [S]), is the foundation. Km reflects substrate affinity (low Km = high affinity). Vmax reflects the maximum catalytic rate. Enzyme inhibitors are crucial in pharmacology.
| Inhibition Type | Mechanism | Effect on Km | Effect on Vmax |
|---|---|---|---|
| Competitive | Inhibitor binds to active site. | Increases (lower affinity) | Unchanged |
| Non-competitive | Inhibitor binds to allosteric site. | Unchanged | Decreases |
| Uncompetitive | Inhibitor binds only to ES complex. | Decreases | Decreases |
Interactive Practice Quiz
Rigorously test your understanding of these advanced concepts. Choose the best answer for each question and then submit to see your results.