- caused by treatment, usually undesirable

Iatrogenic

- relating to a hospital

- IE- infections

Nosocomial

- measurable or observable manifestation of disease

- objective evidence

Sign

- manifestation of disease reported by pt

- subject evidence

Symptom

- disability due to disease

- diseased condition or state

Morbidity

- signs/symptoms diagnostic of Dx

Pathognomonic features

- early symptoms of Dx, usually before diagnostic features manifest

- indicates onset of Dx

Prodrome

- recovery stage of a Dx

- period between end of Dx and restoration to health

Convalescence

- complete absence of structure or tissue due to failure to develop or no development beyond rudimentary angle

Agenesis/Aplasia

- arrested or diminished development

- failure to attain normal size

- left heart syndrome, pulmonary with congenital diaphragmatic hernias

Hypoplasia

- normal tissue in an abnormal location

- adrenal in spermatic cord, pancreas in GI tract

Ectopia, heterotopia, choristoma, "rests"

- non-migration

- "horseshoe kidney"

Dystopia

- disorganized growth

- cells are generally normal, organization is abnormal

Dysplasia

- distinct mass, tumor-like overgrowth of normal mature tissues that are native to that site

- pulmonary and renal

Hamartoma

- reduction in size of either whole organ or single cells

- may be associated with reduction of cell numbers or shrinkage of cells (irreversible/reversible)

- caused by ischemia or "disuse"

- may physiologic or pathologic

Atrophy

- reduction in size after a period of normal growth or hyperplasia

- IE- reduction in breast size after lactation

Involution

- increased size of cells or organs

- caused by increased workload, neural or hormonal stimulation

- involved cells show increased synthesis of structural components, expression of related genes, resistance to apoptotic signals

- may endanger survival if metabolic demands outstrip the blood supply

Hypertrophy

- increased number of cells

- occurring in tissue w/ mitotic capabilities

- frequently occurs with hypertrophy

Hyperplasia

- change in a differentiated cell type

- local proliferative cells respond to change in environment

- Eg: smoker's simple columnar --> stratified squamous

- generally named by the new cell type

- usually from prolonged irritation or stress

Metaplasia

- most common type of metaplasia

- bronchi of smokers, endocervix, urinary bladder

Squamous metaplasia

- urothelium replaced by mucous columnar cells

- gastric type mucous columnar cells replaced by goblet-cells

- Barrett's esophagus (goblet cells)

Intestinal (Glandular) metaplasia

- Oxygen deprivation, physical, chemical, infectious agents, immunologic reactions & inflammation

- genetic derangements

- nutritional imbalances

Causes of Cellular injury

- cell membrane integrity

- aerobic respiration

- protein synthesis

- maintenance of genetic integrity

Processes vulnerable to injury

- increased cytosolic H2O with cellular swelling

- ATP depletion and decreased synthesis

- Mitochondrial damage

- loss of calcium homeostasis

- production of oxygen radicals

- defects in membrane permeability

Changes that occur with cellular injury

- most common immediate cause of cell injury

- "final common pathway" for many etiologic agents

- decreased oxygen at a cellular level

Hypoxia

- decreased blood supply (ischemia)

- diminished oxygen carrying capacity of blood (CO)

- poisoning of oxidative enzymes (cyanide)

Mechanisms for hypoxia

- most susceptible cells to hypoxia

Neurons

- if hypoxia not sustained, decreased oxygen tension --> decreased production of ATP

- decreased ATP leads to diminished activity of Na pump

- Influx of sodium, Cl, and H2O, efflux of K

- acute cellular swelling w/ organelles

- increased anaerobic glycolysis --> decreased pH

- detachment of ribosomes from rough ER --> decreased protein synthesis, fatty degeneration

Reversible changes of hypoxia

- heavy, enlarged pale organ

- hydropic swelling, intracellular edema, hydropic degeneration, cloudy swelling

Cellular swelling

- extensive damage to plasma and organelle membranes

- release of reactive oxygen species

- phospholipase activation

- detergent action of toxic lipid breakdown

- decreased phospholipid synthesis

- influx of calcium, lysis of lysosomes

- amorphous densities, high amplitude swelling of mitochondria

Effects of irreversible cellular injury

- major final common pathway in cellular injury

- initiated by ionizing radiation, oxidative reactions of normal metabolism

- metabolism of exogenous chemicals

- effects include membrane, protein, DNA damage

- inactivated by spontaneous decay, antioxidants, enzymes

Reactive Oxygen Species (ROS) injury

- occurs following ischemia of intermediate duration

- short duration live, long duration die

- associated w/ overproduction of reactive oxygen species

- ischemia causes ATP catabolism & free radical production

- purines produced as by-product of ATP catabolism

- xanthine oxidase to produce uric acid w/ ROS

- influx of neutrophils in response to inflammation

Re-perfusion injury

- "self-digestion"

- cell death in context of the death of an organism

- release of intracellular enzymes breaks down adjacent structures

Autolysis

- localized areas of cell death in surrounding living tissue

- types: coagulative, liquefactive, caseous, fat

- microscopic: pyknosis, karyolysis, karyorrhexis

- loses internal features, deeply eosinophilic

Necrosis

- shrunken nuclei and condensed chromatin

- microscopic recognition of necrosis

Pyknosis

- nucleus dissolves evenly and diffusely

- microscopic recognition of necrosis

Karyolysis

- nucleus fragments into granular debris

- microscopic recognition of necrosis

Karyorrhexis

- most common pattern of necrosis

- found in most organs except CNS

- usually caused by ischemia "infarction"

- denaturation of cell proteins after cell death

- dead cells, but appear intact for a while

- no nuclei, cytoplasmic detail lost, replaced by scar tissue

Coagulative necrosis

- found in the brain

- infiltration by neutrophils (pus) in most organs, producing cystic spaces filled with pus (abscesses)

- dead tissue digested faster than body can repair

- associated with neural tissue, neutrophils, bacteria

- lipid-laden macrophages at periphery of lesion

Liquefactive Necrosis

- found in any organ infected by appropriate organism

- lungs and lymph nodes most common

- tuberculosis, mycobacterium, and fungi can cause it

- cell walls contain complex waxes that prevent complete removal of dead cellular structures

- crumbly shapeless white curd-like debris

- granulatomatous inflammation (but not all granulomas have this)

Caseous inflammation

- found in adipose tissue, especially abdominal and peripancreatic

- caused by release of hydrolytic enzymes from pancreatic damage, trauma (subcut tissues and breasts)

- lipases hydrolyze fats to fatty acids, combine with Ca to form insoluble soaps

- Chalky white deposits

- faintly basophilic staining material outline fat cells

Fat Necrosis

- autonomous growth, generally as a result of mutations

- "clonal" proliferation of cells

- later mutations may result in increased aggressiveness

Neoplasia

- clonal autonomous growth of cells

- benign, uncertain of potential, malignant

Neoplasm

- any swelling

- used almost exclusively with a "neoplasm" now

Tumor

- mass which protrudes beyond the surface of a hollow organ

- broad-based (sessile), narrow-based (pedunculated)

- smooth or have finger-like projections (papillary)

Polyp

- capable of invading and/or metastasizing

- collectively referred to as cancer

Malignant

- premalignant disordered cell growth

- neoplastic and normal cells coexist w/o invasion

- clonal population of cells

- not cancer

Dysplasia (in context of neoplasia)

- cancer that is still confined to a natural boundary

- carcinoma that has completely replaced the normal epithelium, yet still confined by basement membrane

In-situ

- dysplasia and carcinoma-in-situ

- Eg: cervical, prostatic

Intra-epithelial neoplasia

- cancer arising from epithelium

- most common type of cancer

- metastasize first by way of lymphatics, then bloodstream

Carcinoma

- arising from structural tissies (mesenchymal)

- tend to metastasize by way of bloodstream (to lungs especially), but not lymph nodes

Sarcoma

- Low --> High

- well differentiated --> poorly differentiated

- often used as predictor of behavior of tumor

Cancer Grade

- extent of the spread of a neoplasm

- predictor of outcome

- I-IV

- tumor, node, metastases (TMN)

Cancer Stage

- metaplasia, dysplasia, carcinoma-in-situ, carcinoma

Developmental Steps of Neoplasia