Pathology and inflammation Flashcards
hyperplasia
increase in number of cells in response to increased stimulation or stress; may be pathological (menopausal endometrial hyperplasia, skin warts) or physiological (breast hyperplasia during puberty and pregnancy, wound healing); reversible, but may increase cancer risk
hypertrophy
increase in size of existing cells in response to increased stimulation or stress, particularly trophic or mechanical triggers; includes enlarged nuclei and an increase in proteins and organelles in the cells; often leads to an increase in the size of the corresponding organ; may be pathological (hypertensive cardiac hypertrophy) or physiological (increased muscle mass in response to exercise)
atrophy
decrease in size of existing cells; includes decreased protein synthesis, increased degradation, decreased cell function (NOT cell death); may be pathological (muscle atrophy due to peripheral nerve damage) or physiological (menopausal endometrial atrophy)
metaplasia
change in cell/tissue type via reprogramming of stem cells in response to increased stimulation or stress; may increase cancer risk
ischemia
reduced or absent blood flow to a particular tissue
necrosis
form of cell death due to irreversible cell injury; features include increased eosinophilia, nuclear shrinkage/fragmentation/disappearance, breakdown of plasma membrane
hydropic change/vacuolar degeneration
form of reversible cell injury; cells swell and exhibit membrane blebs, as well as vacuoles corresponding to distended endoplasmic reticulum; results from failure of membrane pumps to maintain homeostasis; example: acute tubular necrosis due to reperfusion injury
fatty change
form of reversible cell injury due to toxic or hypoxic stress; appearance of lipid vacuoles in cell cytoplasm; primarily in cells dependent on fat metabolism, when fatty acid transport systems are intact but degradative enzymes are damaged/deficient; example: fatty liver disease due to alcohol use or obesity
liquefactive necrosis
necrotic pattern caused by bacterial/fungal infection or brain infarct; features include complete tissue digestion/semi-liquid consistency, presence of PMNs, pus/abscesses, no residual tissue architecture
coagulative necrosis
necrotic pattern caused by hypoxic or anoxic injury due to ischemia; features include persistence of dead cells, intact outlines/tissue architecture, loss of cellular details; common in solid organs (except the brain); generally presents as wedge shape that points to the infarct
caseous necrosis
necrotic pattern characteristic of tuberculosis infection; features include cheese-like appearance, fragmented/coagulated cells with loss of tissue architecture/cell outlines, surrounded by granuloma
gangrenous necrosis
necrotic pattern describing ischemic coagulative necrosis of extremities or GI organs; “dry” when strictly ischemic, “wet” when also infected (shows liquefactive characteristics); features similar to coagulative necrosis, include black discoloration of tissue
fat necrosis
necrotic pattern caused by injury/trauma to fatty tissue, which causes lipase release, liberation of fatty acids, and subsequent calcium saponification; features include chalky white appearance of tissue; typical of acute pancreatitis or trauma to the breast
fibrinoid necrosis
necrotic pattern caused by deposition of immune complexes along vascular walls; features include fibrin-like, bright pink, amorphous appearance; typical of vasculitis
antigen
a molecule that stimulates an adaptive immune response
epitope
specific region of a macromolecular antigen to which lymphocyte receptors bind
immunogen
a molecule that induces an immune response (may or may not include a lymphocyte response)
labile cells
continuously-dividing cells (examples: hematopoietic cells, surface epithelia)
stable/quiescent cells
tissues that normally have minimal/no replicative activity, but are capable of proliferation in response to injury (examples: solid organ parenchyma, endothelial cells, fibroblasts, smooth muscle cells)
permanent cells
non-proliferative tissues, even in the presence of cell stress/injury (examples: neurons, cardiac muscle cells)
reperfusion injury
tissue damage caused by sudden rapid increase of ROS production due to reperfusion following ischemia, as well as accompanying inflammation induced by ROS injury
lipofuscin
indigestible material resulting from lipid peroxidation; “wear and tear” pigment, increases with aging; visible in heart, liver, and brain
anthracosis
carbon pigment that accumulates in lung tissue/lymph nodes; inhaled in air, then phagocytosed by alveolar macrophages and carried to lymph nodes; common in city-dwellers, coal miners, and smokers
hemosiderin
hemoglobin-derived pigment containing iron (yellow to golden brown), present in tissue where there has been hemorrhage, systemic deposition present with increased iron absorption, some anemias, transfusions, and some hereditary conditions
dystrophic calcification
calcification of non-viable, damaged, or dying tissues in the presence of normal serum calcium levels; tissue is basophilic on H&E; examples include atheromas, aortic valves in the elderly, lymph nodes with long-standing TB
metastatic calcification
calcification of normal tissues due to increased serum calcium levels (i.e. elevated parathyroid hormone, destruction of bone, vitamin D intoxication, renal failure); common in interstitial tissues of lung, kidney, and gastric mucosa
Barrett’s esophogus
metaplasia of the distal esophagus in which esophageal squamous epithelium (normal) changes into glandular epithelium similar to that of the gastric mucosa in response to chronic acid reflux; protects the esophagus from damage by stomach acid, but predisposes for glandular carcinoma
myositis ossificans
ossification of muscle due to trauma or injury
type I diabetes
Type IV autoimmune disease caused by production of pathogenic T-cells against pancreatic islet antigens; characterized by impaired glucose metabolism and vascular disease
IPEX
immune dysregulation, polyendocrinopathy, enteropathy, X-linked; autoimmune disease caused by mutations in Foxp3/loss of T-regs, affects infant boys; characterized by inflammatory bowel disease, severe eczema, food allergies, T1DM, thyroiditis, autoimmune hemolytic anemia, thrombocytopenia, hypergammaglobulinemia, very high IgE levels; lethal if not treated aggressively
celiac disease
gluten enteropathy in which gladden in food is altered upon binding to tissue-transglutaminase to become immunogenic; possible molecular mimicry between tissue-transglutaminase and intestinal wall mediates Ab response
CH50
total complement activity; used to test for complement defects; if result is low, then individual component testing should be ordered
dihydrorhodamine test
diagnostic test for chronic granulomatous disease; DHR is oxidized by PMNs when stimulated with forbid myristate acetate, oxidized form is fluorescent, absence of fluorescence = positive for CGD
chronic granulomatous disease
usually presents by age 2; caused by functional absence of respiratory burst in neutrophils and monocytes (mutation in any of four subunits in NADPH oxidase), though hypomorphic protein may be able to handle most microbes; may be X-linked; pts present with pneumonia, adenopathy/abscesses (hepatic abscess common), sepsis, osteomyelitis, infection with catalase (+) bacteria; Dx req’s DHR or NBT (DHR preferred)
leukocyte adhesion deficiency
caused by mutation in LAD-1/Mac-1 (common integrin beta chain for CD18), LAD-2 (only in middle east), or other integrins, which leads to impaired leucocyte chemotaxis, phagocytosis, and margination; pts present with recurrent pyogenic infections, delayed umbilical cord detachment, leucocytosis, inability to form pus; infections require aggressive Abx treatment, bone marrow transplant in severe cases
CBC with differential
complete blood count that includes specific counts of neutrophils, lymphocytes, monocytes, basophils, and eosinophils
ANC
absolute neutrophil count - important to diagnose neutrophil defects, including chronic granulomatous disease, congenital/cyclic neutropenia, and leukocyte adhesion deficiency
delayed-type hypersensitivity
Type IV hypersensitivity reaction, T-cell mediated, leads to macrophage activation, cytokine-mediated inflammation, cell lysis
DiGeorge syndrome
AKA 22q11.2 deletion syndrome; caused by a micro deletion in chromosome 22q11.2 on the TBX1 gene (homeobox); clinical syndrome characterized by CATCH22 (cardiac defects, abnormal facies, thymic hypoplasia, cleft palate, hypocalcemia, 22nd chromosome); also commonly exhibit immunodeficiency/autoimmunity; Dx req’s FISH, chromosomal microarray/DNA duplication test
common variable immunodeficiency
most common clinically-significant Ab deficiency; onset at any age (>2 y.o.), no known monogenic cause; characterized by low IgG and low IgA or IgM, lymphocyte levels generally normal; pts present with frequent URI/GI infections and bronchiectasis/interstitial lung disease, often die of pulmonary disease, cancer, autoimmune complications, liver disease, or infection; Dx based on Ig count, absent isohemagglutinins, poor vaccine response (pneumavax)
agammaglobulinemia
presents within first year of life, often X-linked (XLA); X-linked form caused by mutation in Btk gene (part of surrogate light chain signaling pathway), leading to lack of B cells (failure to differentiate) and panhypoglobulinemia; pts present with recurrent otitis, sinusitis, pneumonia, untreated may lead to bronchiectasis and infection with encapsulated bacteria or mycoplasma spp.; also have severe enteroviral infections (vaccine-related polio); Dx req’s quantitative Ig (IgG, IgA, IgM), flow cytometry; Tx with IV globulin
complement deficiency
may present at any age; early complement (C2, C4) defects present with sinopulmonary infections, increased susceptibility to S. pneumoniae and H. influenzae, autoimmune disease (such as SLE or glomerulonephritis); late complement (C5-C9) defects present with increased susceptibility to Neisserial infections (generally present with first infection at ~17 y.o.); C3 defects are very rare and present with severe pyogenic infections; diagnostic testing includes CH50 (only complement deficiency if CH50 = 0 - if it’s low, then it’s a consumption issue, like lupus)
systemic lupus erythematosus
Type III autoimmune disease caused by antibody production against sDNA, histones, and other nuclear proteins, which leads to immune complex deposition; characterized by anti-nuclear antibody (ANA) production, nephritis, rash (malaria, discoid), and vasculitis; complement defects lead to early onset
TREC (T-cell receptor excision circles)
nonreplicating circular pieces of DNA in naive T-cells generated in the process of making a T-cell receptor; measured via real-time qPCR; low levels diagnostic of SCID
rheumatoid arthritis
Type IV autoimmune disease caused by T-cell-mediated (likely B-cell also) inflammation of the joints/reactivity to joint antigens; pathology includes pants formation, aggregates of mononuclear cells; oligoclonal T-cells release IL-1, IL-6, and TNF, which activate macrophages/inflammation; B-cells aggregate in synovium
multiple sclerosis
Type IV autoimmune disease caused by production of pathogenic T cells agains myelin proteins; characterized by demyelination of neurons in the central nervous system by T-cells and macrophages, sensory and motor dysfunction
X-linked SCID
severe combined immunodeficiency; most common etiology of SCID, caused by a mutation in the gamma-chain of the IL-2 receptor, which prevents both T-cell survival and B-cell activation by T-cells (gamma chain is also a shared component for other IL receptors); presents within first year of life, usually around 3 m.o.; pts lack T cells and NK cells (though they may possess mom’s T-cells if they crossed the placenta during birth), B cells are present but nonfunctional; characterized by pneumocystis pneumonia, otitis media, thrush, intractable diarrhea, FTT; 100% mortality w/o bone marrow transplant; Dx req’s CBC, lymphocyte enumeration (should lack naive T-cells)
APECED
autoimmune polyendocrinopathy candidiasis ectodermal dystrophy - an autoimmune adrenal and parathyroid disease caused by a defect in the AIRE gene (transcription factor directing expression of self antigens in the thymus); features include hypothyroidism, hypogonadism, vitiligo, pernicious anemia, fungal infections
autoimmune lymphoproliferative syndrome (ALPS)
autoimmune disease caused by mutations in Fas or Fas-L, leads to failed central tolerance; characterized by lymphadenopathy, splenomegaly, autoimmune cytopenias, elevated IgG, IgA, and IgM, elevated double-negative T-cells
