Cell Injury / Adaptive Response - exam 1 Flashcards
Syndrome
cluster of related symptoms and/or signs typically due to a single cause in a patient
Pathogenesis
sequence of events by which the disease develops
Pathognomonic
a particular abnormality found only in one condition (“classic” for particular disease)
Forme fruste
very mild variant of a more serious disease
Incidence
number of new cases per unit of type (cases per 100,000 people per year)
Prevalence
number of cases at any one time (cases per 100,000 people)
What hurts a cell?
- hypoxia: #1 cause
- poor nutrition
- infections agents
- immune injury
- chemical agents
- physical agents
Hypoxia
- 3 mechanisms: ischemia, hypoexmia, failure of oxidative phosphorylation
- Ischemia and hypoxemia can be fixed clinically
- can’t fix failure of oxidative phosphorylation as we can’t make cells use O2
Ischemia
- also called ischemic hypoxia
- lack of arterial blood flow (occlusions)
- pump failure
Hypoxemia
-also called hypoxic hypoxia
-low O2 in the blood
-failure to ventilate or perfuse lungs
-failure of lungs to oxygenate blood
-inadequate RBC mass
Inability of hemoglobin to carry/release O2
-pumps are vessels are fine, but the blood does not carry O2 properly
Failure of oxidative phosphorylation
- also called histotonix hypoxia
- cells are not using O2 properly
- ex: cyanide, carbon monoxide, dinitrophenol
Hypoxic injury
- lack of O2 stops oxidative phosphorylation and electron transport chain; Na+/K+ ATPase fails causing Na+ to stay inside the cell
- anaerobic metabolism leads to lactic acid accumulation and pH drop (due to Na+ staying inside the cell); proteins denatures; leakage of intercellular proteins
- Ca+2 ATPase fails: Ca+2 enters cytoplasm from ECF and ER; irreversible at this point
- Ca+2 entry is key step leading to cell death
Free radical injury
- common mechanism of cell injury
- radicals are unpaired electrons in outer orbital
- damage cell membranes and causes DNA mutations when trying to pair unpaired electrons
- WBC use free radicals to kill invaders, but also hurts normal tissue
- There is limited ability to depose of free radicals
Chemical injury
- depends on nature of poison: acid/alkalis destroy membranes, formaldehyde crosslinks proteins and DNA
- other poisons: cyanide (blocks electron transport chain); chemotherapy (damages DNA); carbon monoxide (replaces O2 on hemoglobin and blocks electron transport chain)
Cellular accumulations and deposits
- can be indicative of cell injury or systemic disease
- 5 main types: triglycerides, glycogen, complex lipids or carbohydrates, pigments, calcium
Triglyceride accumulation
- fatty change, steatosis
- involves liver or heart
- not injurious to cells, but marker for injury
- closely linked to heavy drinking, obesity/metabolic syndrome, malnutrition, outdated tetracycline, ileal bypass surgery
- is reversible if you abstain for a period of time
Glycogen accumulation
- infusion of glucose (dextrose)
- glycogen storage disease (inborn errors of metabolism)
Complex lipids or carbohydrate accumulation
- storage disease (inborn errors of metabolism)
- ex: Gaucher’s, Tay-Sachs’
Pigment accumulation
- Carbon: smoke & soot, enguled by macrophages
- lipofuscin: remnants of interceullar membranes damaged by free radicals (never go away); indicator of oxidative stress; seen in hard working organs
- melanin: produced by melanocytes; two different forms (eumelanin and pheomelanin); hyperpigmentation
- Bilirubin: yellow-orange; product of hemoglobin breakdown; conjugated by liver and excreted in bile
- jaundice: too many red cells being broken down; liver can’t conjugate bilirubin fast enough; biliary obstruction
Calcium accumulation
- calcium phosphate, calcium hydroxide
- dystrophic calcification (wrong place) - can create masses
- normal calcification: pineal glands, airway cartilages, mitral valve annulus, aortic valve sinuses
- abnormal calcification: breast cancer, caseous necrosis of TB, surgical scars, pancreatic necrosis, retained abortions
- metastatic calcification: occur in abnormal places
Cell death
-types: coagulation, liquefactive, caseous, apoptosis
Coagulation necrosis
- usually due to ischemic hypoxia or free radical injury (exception in the brain)
- death of groups of cells
- DNA gets destroyed, but the cell itself stays intact
- dead cells produce acute inflammatory response
- may be replaced by scar, destroyed, walled-off, infected, or even healed
Liquefaction necrosis
- usually due to bacterial infections, poisons, or ischemic hypoxia in CNS
- death of groups of cells
- results from hydrolysis via lysosomal or WBC enzymes “pus”
- cells are completely gone or just a gross gelatinous mass
- no inflammatory process
Caseous necrosis
- also called saponificaiton
- usually due to immune injury in response to certain infections (TB, fungus)
- death of groups of cells
- is less common depending on the pt population
- crumbled, gross-pale, cheesy
- cells are interrupted and nucleus disappears, but they are not completely gone
Apoptosis
- programmed cell death
- two main triggers: mitochondrial damage, death receptors
- usually due to immune response or in response to cellular damage
- single cell death
- cell membrane remain intact
- no inflammatory response
- remains are phagocytized by macrophages
Gross necrosis
- large area cell death
- Dry gangrene: coagulation necrosis; usually no infection
- Wet gangrene: liquefactive necrosis; foul-smelling and infected
Living cell adaptions
- changed in response to stress, injury, or lack of normal stimulation
- these are our responses that try to mitigate our injury
- 5 types: atrophy, hypertrophy, hyperplasia, metaplasia, dysplasia
Atrophy
- response to cell stress or lack of stress
- decrease in cell size not cell number
- generally reversible if stress is taken away (or added)
- ex: loss of breast tissue after menopause, loss of muscle mass inside a cast
- misnomer: involved in cell loss rather than decreased size
Atrophy causes
- loss of motor innervation
- decreased blood supply
- loss of hormonal stimulation
- malnutrition
Hypertrophy
- increase in cell size not increase in number
- ex: skeletal muscle of strength athlete, breast size during pregnancy
Hyperplasia
- increase in cell number
- may be physiologic or pathologic
- ex: female breast at puberty, t-cell response to infection
- generally reversible with removal of stimulatory agent
Hyperplasia causes
- compensatory: growing back
- hormonal stimulation
- genetic mutations: risk for cancer
Metaplasia
- adaptive substitution of one cell type for another
- theoretically reversible
- often involves epithelium in response to a stimulus
- ex:stratified squamous to columnar epithelium in esophagus of people with chronic reflux
Dysplasia
- also called atypia or atypical hyperplasia
- uses in reference to epithelium
- loss of cell uniformity or orientation
- resembles cancer cells, but not invasive yet
- results from genetic mutations to create a growth advantage
- precancerous
- benign: will not invade or spread (usually)
Anaplasia
- confided to an epithelium (dysplasia) or invading (cancer)
- when bizarre cells obtain blood supply a mass is formed
- malignant
Gaucher’s
glucocerebroside
Tay-Sachs’
ganglioside
