Comprehensive Pathophysiology: Genetics, Cellular Concepts, Altered Immunity, and Inflammation

Vocabulary practice flashcards providing precise definitions and clinical correlates across all four core curriculum modules: genetics and chromosomal anomalies, general pathophysiology concepts and social determinants of health (SDOH), altered immunity and hypersensitivities, and acute/chronic inflammatory mechanisms.

Genotype

The specific genetic makeup or combination of genes an individual inherits from their parents that directs internal biological programming, growth, and development.

Phenotype

Any observable physical, biochemical, clinical, or measurable characteristic of an organism (such as eye color, hair color, height, or blood type) produced by the interaction of genotype and environmental factors.

Karyotype

A visual photographic display of an individual's complete set of chromosomes arranged by number and size, utilized clinically to detect chromosomal anomalies such as aneuploidies or structural translocations.

Mitosis

The somatic cell replication process wherein a single parent cell duplicates its DNA and undergoes one nuclear division to produce $2$ genetically identical daughter cells, each retaining the full complement of $46$ chromosomes ($23$ pairs), used for body growth and tissue repair.

Meiosis

The specialized two-stage cell division occurring in reproductive organs (testes and ovaries) that generates $4$ genetically unique haploid gametes (sperm or egg cells), each containing $23$ individual chromosomes.

Base-Pair Substitution (Point Mutation)

A genetic alteration in which a single nucleotide base is swapped for another; it may be silent or may alter a single amino acid in the encoded polypeptide chain (as seen in sickle cell anemia).

Frameshift Mutation

A genetic mutation caused by the insertion or deletion of nucleotide bases in numbers not divisible by three, which shifts the entire downstream triplet reading frame and typically causes catastrophic disruption of the resulting protein.

Aneuploidy

An abnormal chromosomal number deviating from the standard human complement of $23$ chromosome pairs ($46$ total chromosomes), commonly arising from nondisjunction during meiotic division.

Trisomy 21 (Down Syndrome)

An autosomal aneuploidy caused by an extra copy of chromosome 21 (occurring in $1\text{ in }800$ to $1\text{ in }1{,}000$ live births), characterized clinically by hypotonia, low nasal bridge, epicanthal folds, protruding tongue, low-set ears, congenital heart defects, and an increased risk of leukemia.

Klinefelter Syndrome

A sex chromosome aneuploidy occurring in $1\text{ in }1{,}000$ male births where an individual possesses one or more extra X chromosomes (e.g., $47\text{, }XXY$; $48\text{, }XXXY$), causing testicular atrophy, lack of testosterone, infertility, tall stature with long extremities, and gynecomastia.

Cri du Chat Syndrome

A genetic disorder resulting from a deletion of the short arm of chromosome 5, manifested clinically by severe intellectual disability, microcephaly, congenital heart anomalies, and an infant cry resembling a meowing cat.

Marfan Syndrome

An autosomal dominant connective tissue disorder caused by a gene mutation on chromosome 15, resulting in tall and thin stature, arachnodactyly, pectus deformities, ocular lens dislocation, and life-threatening aortic aneurysm or dissection.

Albinism

An autosomal recessive condition characterized by an absence of melanin pigment in the skin, hair, and eyes due to a deficiency in the enzyme tyrosinase, which impairs the conversion of tyrosine to dopa.

Cystic Fibrosis

An inherited autosomal recessive disease that leads to thick, tenacious exocrine gland mucus secretions that obstruct the respiratory, gastrointestinal, and reproductive tracts, often presenting with salty-tasting skin and respiratory failure.

Duchenne Muscular Dystrophy

An X-linked recessive disorder characterized by a complete deficiency of the structural protein dystrophin, which compromises muscle cell membrane integrity and results in progressive skeletal muscle wasting.

Teratogen

Any environmental chemical, physical agent, pharmaceutical drug, or intrauterine infection that impairs normal embryonic or fetal morphogenesis and leads to congenital malformations.

TORCH Complex

An acronym representing maternal infections that can cross the placenta to cause severe fetal injury: Toxoplasmosis, Others (such as hepatitis B, coxsackievirus B, mumps, and poliovirus), Rubella, Cytomegalovirus, and Herpes simplex virus.

Peak Embryonic Vulnerability Window

The fourth and fifth weeks of gestation (within the critical $3\text{ to }9\text{-week}$ embryonic period), during which developing organs undergo rapid organogenesis and exhibit maximum susceptibility to teratogenic disruption.

Pathogenesis

The specific sequence of cellular, biochemical, and histological events that unfold from initial exposure to an etiological agent through the development and progression of a disease.

Primary Prevention

Healthcare interventions aimed at preventing disease or injury before biological pathology occurs through general wellness promotion and specific risk reductions (e.g., immunizations, wearing bicycle helmets).

Secondary Prevention

Clinical practices focused on the early detection and prompt diagnosis of asymptomatic disease to arrest its progress and prevent worsening disability (e.g., routine blood pressure screenings, Pap smears).

Tertiary Prevention

Rehabilitative and therapeutic interventions initiated after a disease has been clinically diagnosed to restore functional capacity, minimize disability, and prevent future recurrences (e.g., physical therapy post-stroke, chronic pharmacotherapy).

Homeostasis

A dynamic, steady state of internal physiological equilibrium maintained through self-regulating feedback mechanisms that monitor and adjust biological parameters within set ranges.

Negative Feedback

The most common homeostatic control mechanism, which functions by opposing or counteracting an initiating deviation from a set point to restore baseline physiological parameters (e.g., insulin lowering elevated blood glucose levels; TSH regulating T3/T4 secretion).

Positive Feedback

A biological feedback mechanism that amplifies and accelerates the initiating stimulus rather than reversing it, driving a physiological process toward completion (e.g., oxytocin-mediated uterine contractions during labor, blood clotting cascade).

General Adaptation Syndrome (GAS)

The body's three-stage non-specific physiological response to sustained stressors, consisting of the Alarm Stage (HPA axis and fight-or-flight arousal), Resistance/Adaptation Stage (resource mobilization to manage stress), and Exhaustion Stage (system failure and disease onset).

Allostatic Load

The cumulative physiological wear and tear experienced by the brain and neuroendocrine-immune systems over time as a result of repeated exposure to chronic stress mediators such as catecholamines and cortisol.

Allostatic Overload

A state of severe physiological exhaustion occurring when prolonged stress depletes adaptive reserve, preventing a return to homeostatic baseline and precipitating diseases of adaptation or organ breakdown.

Cellular Adaptation Patterns

Reversible changes in the size, number, phenotype, metabolic activity, or organization of cells in response to persistent sublethal environmental stresses, illustrated histologically by atrophy, hypertrophy, hyperplasia, metaplasia, and dysplasia.

Atrophy

A reversible decrease in individual cell size and functional capacity resulting from reduced workload, denervation, ischemia, inadequate nutrition, or loss of endocrine stimulation.

Hypertrophy

An increase in the size of individual parenchymal cells leading to an increase in overall organ volume, typically observed in non-dividing tissues subjected to increased hemodynamic or physical workload (e.g., myocardial hypertrophy).

Hyperplasia

An increase in the absolute number of parenchymal cells within an organ or tissue resulting from accelerated mitotic division in cells capable of replication.

Metaplasia

A reversible cellular adaptation in which one adult, mature, differentiated cell type is substituted by another adult cell type better suited to withstand chronic local mechanical or chemical irritation.

Dysplasia

Deranged, atypical cellular growth characterized by abnormal variations in cell size, shape, nuclear architecture, and tissue organization, frequently regarded as a potential precursor to neoplastic malignancy.

Necrosis vs. Apoptosis Pathways

The two pathways of cell death: necrosis is uncontrolled cell lysis with organellar swelling and cellular disruption triggering inflammation; apoptosis is controlled programmed cell destruction characterized by chromatin condensation and apoptotic body phagocytosis without inflammatory response.

Social Determinants of Health (SDOH)

The non-medical conditions in the environments where people are born, grow, live, work, worship, and age that influence health, functioning, quality of life, and disease outcomes, organized into five domains: Economic Stability, Education Access & Quality, Health Care Access & Quality, Neighborhood & Built Environment, and Social & Community Context.

Healthy People 2030

A national, data-driven initiative spearheaded by the U.S. Department of Health and Human Services (HHS/ODPHP) establishing measurable 10-year goals to eliminate health disparities, improve health literacy, foster healthy environments, and advance health equity.

Primary Immune Deficiency

A congenital disorder present from birth, typically resulting from spontaneous genetic mutations in immune stem lines, where a fundamental component of the immune system fails to develop or function normally.

Severe Combined Immune Deficiency (SCID)

A life-threatening primary immunodeficiency caused by an inherited or spontaneous genetic defect that abolishes both functional B and T lymphocytes, leaving infants defenseless against routine pathogens and requiring strict reverse isolation.

Secondary Immune Deficiency

An acquired impairment of an originally intact immune system caused by extrinsic factors such as systemic illness, severe protein malnutrition, immunosuppressive medications (e.g., prednisone, chemotherapy), physical trauma, or viral infection (HIV).

Type I Hypersensitivity

An immediate, IgE-mediated allergic reaction wherein an allergen cross-links antigen-specific IgE bound to tissue mast cells, prompting rapid release of histamine and leukotrienes that cause vasodilation, vascular leakage, and smooth-muscle constriction (e.g., anaphylaxis, asthma).

Type II Hypersensitivity

A tissue-specific cytotoxic reaction where circulating IgG or IgM antibodies bind directly to fixed antigens located on target cell surfaces, recruiting complement and phagocytes to destroy the cell or alter receptor signaling (e.g., ABO blood transfusion reactions, Graves disease, Myasthenia gravis).

Type III Hypersensitivity

An immune-complex-mediated reaction in which soluble antigen-antibody clumps form in the circulation, lodge in microvascular filters (such as renal glomeruli, synovial membranes, and vessel walls), and activate complement and neutrophils to induce tissue destruction (e.g., SLE, post-streptococcal glomerulonephritis).

Type IV Hypersensitivity

A delayed cell-mediated immune reaction occurring within $24\text{ to }72\text{ hours}$, driven by sensitized T lymphocytes recruiting and activating macrophages without the direct involvement of antibodies (e.g., PPD tuberculin skin test, poison ivy contact dermatitis).

Autoimmunity

An abnormal immunological state in which the adaptive immune system loses self-tolerance, leading autoantibodies, autoreactive T lymphocytes, or immune complexes to launch targeted attacks against the host's own healthy tissues (e.g., SLE, rheumatoid arthritis, type 1 diabetes).

Alloimmunity

An immune response directed against non-self antigens derived from another member of the same biological species, clinically observed in solid-organ graft rejection, Rh factor isoimmunization during pregnancy, and ABO-incompatible blood transfusions.

Human Immunodeficiency Virus (HIV)

A blood- and fluid-borne retrovirus that selectively targets and depletes CD4+ T-helper lymphocytes through reverse transcription and host genomic integration, progressively impairing adaptive cell-mediated immunity.

Acquired Immunodeficiency Syndrome (AIDS)

The advanced stage of HIV infection clinically diagnosed when an individual's CD4+ T-cell count falls below $200\text{ cells/mm}^3$ (or $<200\text{ cells/}\nu\text{L}$) or upon the presentation of specific AIDS-defining opportunistic infections or malignancies.

Undetectable = Untransmittable (U=U)

The evidence-based clinical reality that individuals living with HIV who maintain an undetectable viral load (fewer than $20\text{ to }50\text{ copies/mL}$) on continuous antiretroviral therapy (ART) for at least $6\text{ months}$ have zero risk of sexually transmitting the virus to partners.

Post-Exposure Prophylaxis (PEP)

An emergency, short-term course of a three-drug antiretroviral regimen that must be initiated within $72\text{ hours}$ of a potential high-risk HIV exposure and continued daily for $28\text{ consecutive days}$ to block viral replication.

Systemic Lupus Erythematosus (SLE)

A chronic systemic autoimmune disease predominantly affecting women of childbearing age ($9:1$ female-to-male ratio), mediated by antinuclear antibodies (ANAs) and immune complexes that cause widespread inflammation, presenting with a malar butterfly rash, photosensitivity, lupus nephritis, and arthritis.

Rheumatoid Arthritis (RA)

A chronic autoimmune disease characterized by autoantibodies (such as rheumatoid factor) attacking the synovial membranes of joints, producing symmetric bilateral inflammation, prolonged morning stiffness exceeding $30\text{ minutes}$, and progressive articular destruction.

Swan-Neck and Boutonnière Deformities

Classic joint deformities seen in advanced rheumatoid arthritis; swan-neck deformity involves hyperextension of the proximal interphalangeal (PIP) joint with flexion of the distal interphalangeal (DIP) joint, while boutonnière deformity involves flexion of the PIP joint and hyperextension of the DIP joint due to chronic synovial inflammation and tendon rupture.

Osteoarthritis vs. Rheumatoid Arthritis Joint Pathology

The distinct articular differences between osteoarthritis (wear-and-tear cartilage thinning where bone ends rub together and form spurs) and rheumatoid arthritis (autoimmune destruction with bone erosion and a swollen, inflamed synovial pannus).

Rubor (Redness)

A cardinal sign of acute inflammation caused by chemical mediators (histamine, prostaglandins) inducing local arteriolar vasodilation, resulting in hyperemic blood flow that turns skin bright pink or red.

Calor (Heat)

A cardinal sign of acute inflammation resulting from arteriolar vasodilation, where warm arterial core blood rushes to the dilated superficial microvasculature, making the inflamed site notably warm to touch.

Tumor (Swelling)

A cardinal sign of acute inflammation caused by increased microvascular permeability, allowing protein-rich plasma exudate to leak across loosened endothelial junctions into interstitial tissue spaces.

Dolor (Pain)

A cardinal sign of acute inflammation provoked when chemical mediators (bradykinin, prostaglandins) and interstitial tissue pressure directly irritate local sensory nerve endings.

Functio Laesa (Loss of Function)

A cardinal sign of acute inflammation reflecting temporary or permanent impairment of movement and weight-bearing due to severe edema, pain reflex splinting, and localized tissue disruption.

Complement System

A plasma protein cascade that defends against pathogens by forming the Membrane Attack Complex (MAC) to lyse bacterial membranes, opsonizing microbes for enhanced phagocytosis, and releasing chemotactic signals to recruit leukocytes.

Clotting (Coagulation) System

A plasma protein system that activates thrombin to convert soluble fibrinogen into a sticky insoluble fibrin meshwork, which arrests active hemorrhage, traps invading microbes, and provides a provisional structural matrix for tissue healing.

Kinin System

A plasma protein cascade activated during tissue damage that generates the vasoactive peptide bradykinin, which promotes localized vasodilation, increases microvascular leakiness, and triggers nociceptor pain signals.

Acute vs. Chronic Inflammation

Acute inflammation is a rapid, self-limiting response (hours to $2\text{ weeks}$) dominated by neutrophils and exudate; chronic inflammation persists beyond $2\text{ weeks}$ (months or years), featuring macrophages, lymphocytes, ongoing tissue destruction, and fibrosis.

Purulent Exudate

A cloudy, thick, yellow-green inflammatory drainage (pus) composed of high concentrations of necrotic white blood cells (neutrophils), degraded cellular debris, and viable or non-viable microorganisms.

Serous Exudate

A clear, watery inflammatory fluid with low protein and cellular content, derived predominantly from blood plasma, commonly observed in mild acute injuries such as blister fluid after a burn.

Resolution (Tissue Regeneration)

The optimal outcome of tissue healing that occurs when the extracellular scaffolding remains intact, permitting surviving parenchymal cells to replicate and completely restore the original $100\%$ structural architecture and specialized function.

Repair (Fibrosis / Scarring)

The healing pathway that occurs when the extracellular matrix framework is destroyed or parenchymal cells are unable to replicate (e.g., cardiac myocytes), resulting in replacement of damaged functional tissue with non-contractile collagen scar tissue.

Primary Intention Healing

Wound healing characterized by minimal tissue loss where clean, sharp surgical margins or laceration edges are approximated directly (e.g., using sutures or staples), leading to rapid epithelialization and minimal scarring.

Secondary Intention Healing

Wound healing involving extensive tissue loss or non-approximated wound edges (e.g., deep pressure injuries, open burns), requiring the tissue defect to fill from the base upward with vascularized granulation tissue, resulting in prolonged repair and prominent scarring.

Tertiary Intention Healing

A wound closure strategy where an infected, heavily contaminated, or severely edematous wound is intentionally left open to drain or debride before undergoing delayed surgical closure once infection has resolved.

Immunoglobulin G (IgG)

The most plentiful circulating antibody class (accounting for $80\%\text{ to }85\%$ of total serum antibodies) that provides sustained humoral defense during secondary immune responses and is the only immunoglobulin capable of crossing the placenta to provide passive protection to the fetus.

Immunoglobulin M (IgM)

The largest immunoglobulin molecule, existing in serum as a pentamer, that is produced first during a primary acute immune response; it serves as a clinical serologic marker for acute infection and is too large to cross the placenta.

Immunoglobulin A (IgA)

The major secretory antibody class ($15\%$ of serum immunoglobulins) concentrated in mucosal secretions (saliva, tears, gastrointestinal and respiratory mucus, and breast milk), acting as an external mucosal shield that blocks pathogen attachment.

Immunoglobulin E (IgE)

A low-concentration serum immunoglobulin ($<1\%$) that binds with high affinity to Fc receptors on mast cells and basophils, mediating Type I hypersensitivity reactions (allergies, anaphylaxis) and defense against parasitic helminths.

Immunoglobulin D (IgD)

An immunoglobulin class comprising less than $1\%$ of serum antibodies, serving primarily as an antigen receptor on the surface of mature, circulating B lymphocytes to guide B-cell activation.