Meditaliano IMAT Prep

Part 1: The Cardiovascular System and Cardiac Physiology

This section delves into the mechanics and regulation of the heart and circulation, the system responsible for transport and perfusion.

1.1 Cardiac Electrophysiology

The heart's electrical activity is fundamental to its function as a pump. This activity varies between pacemaker cells and contractile cells.

• Ventricular Action Potential: This is the potential in contractile myocytes.
  1. Phase 0 (Rapid Depolarization): Fast voltage-gated Na⁺ channels open.
  2. Phase 1 (Initial Repolarization): Na⁺ channels inactivate; transient K⁺ channels open.
  3. Phase 2 (Plateau): Influx of Ca²⁺ through L-type Ca²⁺ channels balances K⁺ efflux. This prolonged depolarization is crucial for preventing tetanus and allowing time for ejection.
  4. Phase 3 (Rapid Repolarization): Ca²⁺ channels inactivate; slow delayed-rectifier K⁺ channels open, leading to massive K⁺ efflux.
  5. Phase 4 (Resting Potential): Maintained by the Na⁺/K⁺ pump and K⁺ leak channels.
• Pacemaker Action Potential (SA Node): These cells exhibit automaticity.
  1. Phase 4 (Pacemaker Potential): Slow, spontaneous depolarization due to "funny" current (I_f) channels allowing Na⁺ influx.
  2. Phase 0 (Depolarization): Opening of L-type Ca²⁺ channels (not fast Na⁺ channels).
  3. Phase 3 (Repolarization): Opening of K⁺ channels.
• Electrocardiogram (ECG): A surface recording of the heart's summed electrical activity.
  • P wave: Atrial depolarization.
  • PR interval: Represents the conduction delay through the AV node, allowing ventricles to fill.
  • QRS complex: Ventricular depolarization.
  • T wave: Ventricular repolarization.

1.2 Cardiac Mechanics and Regulation

• Excitation-Contraction Coupling: The process linking the action potential to muscle contraction. In cardiac muscle, this involves Calcium-Induced Calcium Release (CICR). The Ca²⁺ influx during Phase 2 of the action potential is not enough to cause contraction directly; instead, it binds to ryanodine receptors on the sarcoplasmic reticulum (SR), triggering the release of a much larger store of Ca²⁺ from the SR.
• Frank-Starling's Law: This intrinsic property states that the force of contraction is proportional to the initial length of the muscle fibers. In the heart, this means that an increase in end-diastolic volume (preload), due to increased venous return, leads to a more forceful contraction and a greater stroke volume. This ensures the heart automatically pumps out what it receives.
• Cardiac Output (CO): CO = Heart Rate (HR) × Stroke Volume (SV). This is the total volume of blood pumped by the heart per minute.
  • Heart Rate is primarily controlled by the autonomic nervous system's influence on the SA node.
  • Stroke Volume is determined by preload (Starling's Law), afterload (the pressure the heart must pump against), and contractility (the intrinsic strength of the myocardium, influenced by sympathetic stimulation).

1.3 The Vasculature and Hemodynamics

Part 2: Renal, Fluid, and Endocrine Systems

This section explores the kidney's role in maintaining fluid, electrolyte, and acid-base balance, and its integration with the endocrine system.

2.1 Glomerular Filtration and Tubular Function

• Glomerular Filtration Rate (GFR): The volume of fluid filtered from the glomeruli into Bowman's space per unit time (normally ~125 mL/min). It is determined by the balance of Starling forces across the glomerular capillaries. A key feature of the kidney is autoregulation, where mechanisms like the myogenic response and tubuloglomerular feedback maintain a stable GFR despite fluctuations in systemic blood pressure.
• Tubular Transport:
  • Proximal Convoluted Tubule (PCT): The workhorse of reabsorption. Reabsorbs ~65% of filtered Na⁺ and water, and virtually 100% of filtered glucose and amino acids (via Na⁺-coupled secondary active transport).
  • Loop of Henle: Creates the medullary concentration gradient via the countercurrent multiplier mechanism.
  • Distal Tubule & Collecting Duct: The site of "fine-tuning" under hormonal control. Aldosterone acts here to reabsorb Na⁺ and secrete K⁺. ADH acts here to reabsorb water.
• Renal Clearance and Transport Maximum (Tm): Clearance is the volume of plasma from which a substance is completely cleared per unit time. If a substance's clearance is greater than GFR (e.g., PAH), it must be secreted. If it's less than GFR (e.g., glucose), it must be reabsorbed. For substances reabsorbed by carriers, there is a transport maximum (Tm). For glucose, when plasma concentration exceeds the renal threshold (~200 mg/dL), the carriers become saturated (Tm is reached), and glucose spills into the urine (glucosuria).

2.2 Hormonal Regulation of Homeostasis

2.2.1 Renal pH Regulation

The kidneys are the primary organs for long-term pH control, compensating for metabolic acidosis and alkalosis. They do this by:

1. Reabsorbing filtered bicarbonate (HCO₃⁻): Primarily in the PCT. This process is coupled to H⁺ secretion.
2. Generating new bicarbonate: During acidosis, renal tubule cells metabolize glutamine, producing two new HCO₃⁻ molecules (which are returned to the blood) and two NH₄⁺ molecules (which are secreted into the urine).
3. Secreting H⁺: H⁺ is actively secreted into the tubule and buffered in the urine by phosphate and ammonia (NH₃).

Part 3: Immunity and Digestive Physiology

This section integrates the body's defense mechanisms with the processes of digestion and absorption.

3.1 Principles of Immunity

• Innate vs. Adaptive Immunity: Innate immunity provides a rapid, non-specific first line of defense (e.g., phagocytes, complement). Adaptive immunity is slower, highly specific, and has memory (e.g., T cells and B cells).
• Antigen Presentation: This is the crucial link between innate and adaptive immunity. Antigen-presenting cells (APCs) like dendritic cells process and present antigens on MHC molecules.
  • MHC Class I: Found on all nucleated cells. Presents endogenous antigens (e.g., viral proteins) to CD8⁺ cytotoxic T lymphocytes (CTLs). CTLs then kill the infected cell.
  • MHC Class II: Found only on professional APCs (dendritic cells, macrophages, B cells). Presents exogenous antigens (e.g., bacteria that have been phagocytosed) to CD4⁺ helper T cells (Th). Th cells then coordinate the immune response.
• T and B Cell Function: Upon activation (which requires a costimulatory signal, e.g., CD28-B7), helper T cells orchestrate the immune response by releasing cytokines. Cytotoxic T cells kill target cells. B cells differentiate into plasma cells, which are antibody factories, providing humoral immunity.

3.2 Advanced Immunological Concepts

3.3 Digestive Physiology

• Phases of Digestion: Digestion is regulated in three phases: the cephalic phase (thought/smell of food), the gastric phase (food in stomach), and the intestinal phase (chyme in duodenum).
• Hormonal Control:
  • Ghrelin: Produced by the stomach; the only major hormone that stimulates hunger.
  • Gastrin: Produced by G cells in the stomach; stimulates HCl secretion from parietal cells.
  • Cholecystokinin (CCK): Produced by the duodenum in response to fats/proteins; stimulates gallbladder contraction and pancreatic enzyme release.
  • Secretin: Produced by the duodenum in response to acid; stimulates pancreatic bicarbonate secretion.
• Bile and Fat Digestion: Bile, produced by the liver and stored in the gallbladder, contains bile salts that emulsify large fat globules into small micelles. This increases the surface area for digestion by pancreatic lipase.
• Enteric Nervous System (ENS): Often called the "second brain," the ENS is a complex network of neurons within the gut wall that can control gut motility and secretion independently of the CNS, though it is modulated by the autonomic nervous system.

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.