2.1 Anatomy

Anatomy is the structural foundation on which pharmacokinetics, pharmacodynamics, and drug delivery rest. The FPGEE expects you to know not only where organs sit but why their structure matters for therapy — why some drugs cannot enter the brain, why oral morphine is less bioavailable than intravenous morphine, and why an injection into the wrong gluteal quadrant can injure the sciatic nerve. This section surveys the body systems that pharmacy practice depends on most, with attention to the anatomical details that change drug behavior.

Major Body Systems and Pharmacy Relevance

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Cardiovascular Anatomy

The heart has four chambers — right atrium, right ventricle, left atrium, left ventricle — separated by the tricuspid (right) and mitral (left) atrioventricular valves and the pulmonary and aortic semilunar valves. The cardiac conduction system begins at the sinoatrial (SA) node in the right atrium, travels through the atrioventricular (AV) node, the bundle of His, and the left and right bundle branches, ending in the Purkinje fibers. This anatomy explains why Class Ia antiarrhythmics act on sodium channels in the conduction tissue, why calcium channel blockers slow AV node conduction, and why beta-blockers reduce SA node firing.

The heart's blood supply comes from the left main coronary artery (which divides into the left anterior descending and left circumflex) and the right coronary artery. A thrombus in the left anterior descending produces an anterior STEMI; occlusion of the right coronary artery often produces inferior STEMI and AV node dysfunction. Drug distribution through the vascular tree depends on vessel wall structure: capillaries have fenestrated endothelium in most tissues, but continuous endothelium in the brain and fenestrated endothelium in the kidneys and intestines.

Respiratory Anatomy

The respiratory tree branches roughly 23 times from trachea to alveoli. The conducting zone (trachea, bronchi, bronchioles down to terminal bronchioles) moves air but does not exchange gas; the respiratory zone (respiratory bronchioles, alveolar ducts, alveolar sacs) performs gas exchange. The alveolar-capillary membrane is only 0.2–0.5 µm thick, which allows inhaled anesthetics and aerosolized bronchodilators like albuterol to reach the bloodstream within seconds. Large airway smooth muscle contains beta-2 receptors — the anatomical basis for beta-2 agonist bronchodilation.

Gastrointestinal Anatomy

The GI tract has four histological layers: mucosa, submucosa, muscularis externa, and serosa. The stomach's parietal cells secrete acid (target of proton pump inhibitors), while chief cells secrete pepsinogen and G cells release gastrin. The small intestine — duodenum, jejunum, ileum — has villi and microvilli that produce ~30 m² of absorptive surface; most oral drugs are absorbed in the jejunum because of its high blood flow and large surface area. The colon harbors ~10¹³ bacteria that can metabolize drugs (e.g., digoxin inactivation by Eggerthella lenta) or activate prodrugs (e.g., sulfasalazine to 5-ASA).

Renal Anatomy and the Nephron

Each kidney contains about 1 million nephrons. The nephron segments, in order, are the glomerulus, proximal convoluted tubule, loop of Henle (descending and ascending limbs), distal convoluted tubule, and collecting duct. The glomerulus filters plasma at a rate of about 120 mL/min in healthy adults (GFR). The proximal tubule reabsorbs all glucose, amino acids, and most sodium; loop diuretics act on the Na-K-2Cl cotransporter in the thick ascending limb; thiazides act on the Na-Cl cotransporter in the distal tubule; and potassium-sparing diuretics act on ENaC in the collecting duct. Knowing the segment-specific transporters explains why combining a loop diuretic with a thiazide produces sequential nephron blockade.

Nervous System Anatomy and the Blood-Brain Barrier

The central nervous system (CNS) consists of the brain and spinal cord; the peripheral nervous system (PNS) includes cranial nerves, spinal nerves, and the autonomic nervous system (sympathetic and parasympathetic). The blood-brain barrier (BBB) is formed by tight junctions between brain capillary endothelial cells, reinforced by astrocytic end-feet. The BBB passively excludes molecules that are large (>500 Da), hydrophilic, or highly protein-bound. Only lipophilic, small molecules cross passively; others require specific carriers (GLUT1 for glucose, LAT1 for levodopa, transferrin receptor for iron). This explains why levodopa — unlike dopamine — enters the brain to treat Parkinson's disease, and why penicillin is largely excluded from CSF in the absence of meningitis.

Endocrine, Musculoskeletal, Integumentary, Reproductive, and Immune/Lymphatic Anatomy

The hypothalamus sits below the thalamus and above the pituitary stalk; it releases releasing hormones that act on the anterior pituitary, which in turn secretes trophic hormones (ACTH, TSH, FSH, LH, GH, prolactin). The posterior pituitary stores and releases vasopressin (ADH) and oxytocin. The adrenal cortex has three zones — glomerulosa (mineralocorticoids), fasciculata (glucocorticoids), reticularis (androgens) — remembered by "GFR" for the layers, not the renal measurement. The pancreatic islets contain beta cells (insulin), alpha cells (glucagon), and delta cells (somatostatin).

The musculoskeletal system provides the sites for intramuscular injections (see below). The integumentary system is dominated by the stratum corneum, the outermost layer of dead keratinocytes that is the rate-limiting barrier for transdermal patches (e.g., fentanyl, nicotine, estrogen). The immune/lymphatic system includes lymph nodes, spleen, thymus, tonsils, and mucosa-associated lymphoid tissue (MALT); subcutaneous injection into lymphatic-rich regions enables slow, sustained absorption of vaccines and proteins like insulin.

Anatomical Landmarks for Drug Delivery

• Intramuscular (IM) sites: deltoid (fastest absorption, used for vaccines and epinephrine), vastus lateralis (preferred in infants), and ventrogluteal (safest adult site — avoids the sciatic nerve). The dorsogluteal site is no longer recommended because of sciatic nerve injury risk.
• Subcutaneous (SC) sites: outer upper arm, abdomen (rapid for insulin), anterior thigh — slower, sustained absorption suitable for enoxaparin, insulin, and vaccines.
• Intravenous (IV) access: antecubital fossa for emergencies, hand veins for peripheral lines, subclavian/internal jugular for central access — 100% bioavailability, immediate onset.
• Topical/transdermal: intact stratum corneum is the rate-limiting barrier; damaged skin (burns, eczema) increases absorption and systemic toxicity risk.
• Intrathecal/intraventricular: direct CSF access bypasses the BBB for methotrexate, baclofen, and certain antibiotics.

Understanding these landmarks lets you predict onset, avoid complications, and counsel patients on injection-site rotation for insulin and low-molecular-weight heparins.