Pathophysiology Flashcards: Cellular Pathology, Adaptations, Inflammation, and Genetic Diseases

Comprehensive vocabulary flashcards covering cell pathology, cellular organelles, gene expression, adaptation, mechanisms of cell injury/death, acute and chronic inflammation, wound repair, and major genetic disorders.

Pathophysiology

The sequence of events from structural and/or functional abnormalities to clinical changes.

Mismatch Diseases

Conditions that arise because human bodies are adapted to an environment different from the one currently inhabited.

Rudolf Virchow

The father of cellular pathology who established cellular changes as the basis of disease and formalized methodical procedures for autopsies.

Single Nucleotide Polymorphism (SNP)

A single nucleotide variant that is almost always biallelic (only two choices, e.g., A or T) occurring across exons, introns, intergenic, and coding regions.

Copy Number Variation (CNV)

A form of genetic variation consisting of different numbers of large contiguous stretches of DNA ranging from $1000\text{ bp}$ to millions of base pairs, responsible for several million base pair differences between individuals.

Epigenetics

The phenomenon in which genetically identical cells express their genomes differently, resulting in phenotypic differences without altering the primary DNA sequence.

Heterochromatin

Condensed chromatin that is genetically inactive and transcriptionally silent.

Euchromatin

Extended, dispersed chromatin that is genetically active and undergoing transcription.

Micro-RNA (miRNA)

Short noncoding RNA molecules ($22\text{ nucleotides}$ on average) that function in post-transcriptional gene regulation by directing RISC to repress mRNA translation or cleave mRNA targets.

Long Noncoding RNA (lncRNA)

Noncoding RNA that modulates gene expression by facilitating transcription factor binding to promote gene activation or binding chromatin to restrict RNA polymerase access.

Cytoskeleton Fibers

A network of protein fibers comprising Microfilaments ($7\text{ nm}$, actin subunits), Intermediate filaments ($10\text{ nm}$, fibrous subunits like lamins, vimentin, desmin), and Microtubules ($25\text{ nm}$, tubulin subunits).

Peroxisome

A membrane-bound organelle containing oxidases and catalase responsible for the formation and degradation of hydrogen peroxide ($H_2O_2$), fatty acid $\beta$-oxidation, and alcohol/lipid detoxification.

Yamanaka Factors

A set of four transcription factors ($Oct3/4$, $Sox2$, $Klf4$, and $c\text{-}Myc$) introduced to reprogram fully differentiated somatic cells into induced pluripotent stem cells (iPS cells).

Hyperplasia

An adaptive increase in the number of cells in an organ or tissue; occurs only in cell populations capable of division.

Hypertrophy

An adaptive increase in the size of individual cells resulting in overall organ enlargement.

Atrophy

A decrease in cell size and mass in a cell that was once of normal size, caused by loss of blood supply, loss of innervation, disuse, or hormonal withdrawal.

Metaplasia

A reversible phenotypic substitution of one adult epithelium type by another adult epithelium type to better withstand a harsh environment.

Superoxide Dismutase (SOD)

An antioxidant enzyme forming the first line of defense against superoxide ($O_2^{\bullet-}$) by converting it to hydrogen peroxide ($H_2O_2$).

Mitochondrial Permeability Transition Pore (MPTP)

A high-conductance inner mitochondrial pore opened by elevated matrix $Ca^{2+}$, reactive oxygen species, and low pH, leading to loss of membrane potential, swelling, and release of pro-apoptotic factors like cytochrome c.

Coagulative Necrosis

A pattern of necrotic cell death characterized by dominant protein denaturation over enzymatic breakdown, preserving general tissue architecture with cytoplasmic eosinophilia.

Liquefactive Necrosis

A pattern of necrotic cell death characterized by dominant enzymatic digestion over denaturation, completely destroying cellular architecture to leave a liquid viscous mass or abscess.

Fat Necrosis

Focal areas of fat destruction resulting from enzymatic lipase release or trauma, where released fatty acids combine with calcium to form visible chalky white deposits.

Caseous Necrosis

A friable, crumbly, "cheesy-looking" pattern of cell death classic to tuberculous mycobacterial infections and granulomatous diseases.

Extrinsic Apoptosis Pathway

A cell death pathway initiated by ligand binding (e.g., FasL, TNF) to membrane death receptors, activating docking proteins (FADD) and procaspase-8, which cleaves executioner caspases-3, 6, and 7.

Lipofuscin

An insoluble, finely granular yellow-brown pigment composed of lipid peroxidation products that accumulates inside lysosomes as cells age ("wear-and-tear pigment").

Dystrophic Calcification

Deposition of calcium salts specifically within damaged, necrotic, or abnormal tissues in patients with normal serum calcium levels.

Metastatic Calcification

Deposition of calcium salts in normal tissues secondary to systemic hypercalcemia (e.g., hyperparathyroidism, bone malignancy, or vitamin D toxicity).

Hemochromatosis

Pathologic systemic accumulation of iron in parenchymal cells of the liver, pancreas, heart, and skin causing organ damage, bronze diabetes, and cirrhosis; stains positive with Prussian blue.

Werner Syndrome (WS)

An autosomal recessive progeria condition caused by mutations in the $WRN$ gene (encoding a DNA helicase), leading to premature aging and death by the 40s or 50s.

Hutchinson-Gilford Progeria Syndrome (HGPS)

An autosomal dominant progeria condition caused by a mutation in the $LMNA$ gene (encoding lamin A), resulting in severe premature aging with an average lifespan of $13\text{ years}$.

Transudate

An extravascular fluid with low protein content and low cellularity resulting from hydrostatic pressure elevation or reduced plasma oncotic pressure, without increased vascular permeability.

Exudate

An inflammatory extravascular fluid with high protein content and high cellular debris resulting from increased microvascular permeability.

Leukocyte Extravasation Cascade

The sequential process of leukocyte recruitment during inflammation involving Margination and Rolling (mediated by selectins), Stable Adhesion (mediated by integrins binding ICAM-1/VCAM-1), Transmigration (PECAM-1/CD31), and Chemotaxis.

Myeloperoxidase (MPO)

An enzyme contained in neutrophil azurophilic granules that converts hydrogen peroxide ($H_2O_2$) and chloride ($Cl^-$) into hypochlorite ($HOCl^-$), a potent antimicrobial agent.

Chronic Granulomatous Disease (CGD)

An immunodeficiency caused by mutations in NADPH oxidase subunits (e.g., X-linked $CYBB$ gene), preventing production of reactive oxygen species and disabling oxidative burst.

Chédiak-Higashi Syndrome

An autosomal recessive disorder caused by a mutation in the $LYST$ gene, impairing microtubule-mediated lysosomal trafficking and resulting in giant lysosomal inclusions, defective phagocytosis, albinism, and neuropathy.

Keloid Scar

An exuberant scar formed by excessive collagen deposition during wound healing that extends beyond the original boundaries of the initial wound.

Pleiotropy

A genetic phenomenon where a mutation in a single gene causes multiple distinct phenotypic traits or organ system abnormalities.

Familial Hypercholesterolemia

An autosomal dominant disorder caused by mutations in the $LDLR$ gene or gain-of-function mutations in $PCSK9$, impairing cellular LDL uptake and causing elevated plasma cholesterol and early atherosclerosis.

Marfan Syndrome

An autosomal dominant connective tissue disorder caused by mutations in the $FBN1$ gene on chromosome $15q21$ (encoding fibrillin-1), leading to skeletal tallness, lens dislocation (ectopia lentis), and aortic root dilation.

Cystic Fibrosis

An autosomal recessive disorder caused by mutations in the $CFTR$ gene on chromosome $7$, resulting in impaired epithelial chloride secretion, dehydrated viscid mucus, recurrent Pseudomonas lung infections, exocrine pancreatic insufficiency, and male infertility.

Phenylketonuria (PKU)

An autosomal recessive metabolic disorder caused by deficiency of phenylalanine hydroxylase (PAH), causing hyperphenylalaninemia, intellectual disability, and hypopigmentation if untreated by dietary restriction.

Gaucher Disease

An autosomal recessive lysosomal storage disease caused by $\beta\text{-glucocerebrosidase}$ ($GBA$) deficiency, resulting in glucocerebroside accumulation in macrophages ("Gaucher cells") with hepatosplenomegaly and bone erosion.

Tay-Sachs Disease

An autosomal recessive lysosomal storage disease caused by a mutation in the $HEXA$ gene (hexosaminidase A deficiency), leading to $GM_2$ ganglioside accumulation in neurons, a retinal cherry-red spot, severe neurodegeneration, and early death.

Duchenne Muscular Dystrophy (DMD)

An X-linked recessive disorder caused by mutations in the dystrophin gene at $Xp21$, producing severe muscular cell membrane weakness, calf pseudohypertrophy, progressive paralysis, and early adult mortality.

Trisomy 21 (Down Syndrome)

A chromosomal disorder ($47,XX/XY,+21$) caused predominantly by maternal meiotic nondisjunction ($95\%$), characterized by intellectual disability, epicanthal folds, flat facial profile, simian crease, cardiac defects, and early Alzheimer disease.

Klinefelter Syndrome

A sex chromosome disorder ($47,XXY$) in males characterized by primary hypogonadism, testicular atrophy, tall stature with long legs, reduced body hair, gynecomastia, and a Barr body.

Turner Syndrome

A sex chromosome disorder ($45,X$) in females characterized by short stature, webbed neck, broad chest with widely spaced nipples, streak ovaries, primary amenorrhea, and coarctation of the aorta.

Fragile X Syndrome

A trinucleotide repeat expansion disorder ($Xq27.3$, $FMR1$ gene) characterized by $>230$ $CGG$ repeats, long facial features, large mandible, macroorchidism, and inherited intellectual disability.

Genomic Imprinting

An epigenetic process where homologous genes are differentially inactivated during gametogenesis; deletion of paternal chromosome $15q12$ causes Prader-Willi syndrome, whereas deletion of maternal $15q12$ causes Angelman syndrome.

Androgen Insensitivity Syndrome (AIS)

An X-linked disorder caused by mutations in the androgen receptor ($AR$) gene in $46,XY$ individuals, resulting in female external genitalia despite male karyotype and elevated serum testosterone levels.