Physiopath Exam 1 Unit 1: Basic terms, cellular adaptations, and abnormal physiological processes Flashcards
homeostasis
the ability of cells to handle normal physiological demands
principle
- generalization that is accepted as true & that can be used as a basis for reasoning or conduct
- a rule or law concerning a natural phenomenon or function of a complex system
4 aspects of a disease that form the core of patho
- etiology
- pathogenesis
- morphologic changes
- function derangements and clinical manifestations
etiology
cause of
pathogenesis
series of steps that occur that manifest the disease
morphologic changes
changes in shape of cell
function derangements & clinical manifestations
- signs: something that can be seen
- symptoms: something that can be felt
focal (vs. diffuse)
localized, exact spot
diffuse (vs. focal)
spread out multiple areas, large area, poorly defined
eosinophilic
looks red, cytoplasm, eosin-loving
basophilic
looks blue, nucleus, hemotoxyin-loving
hyaline (“hyaline change”)
tissue starts to look like cartilage
endogenous
from within
exogenous
from exterior
reactions of body to injury and/or stress
- cellular adaptation
- reversible cell injury
factors affecting ability of a tissue/organ to adapt to an injury/stress
- potential for regeneration
- severity of injury
- duration of injury
- condition of cell
- location of cell
- degree of cell specialization
labile cells
- continuously renewing cell population
- ex. epithelial cells
stable cells
- a (potentially) expanding cell population
- increase # if need to
- ex. hepatocytes, anything with “blast”
permanent cells
- a static cell population
- ex. CNS neurons, cardiac myocytes
how can cells adapt
- atrophy
- hypertrophy
- hyperplasia
- metaplasia
- dysplasia
atrophy
- an adaptation to diminished need or resources for a cells activities
- shrinkage of a cell or organ due to the loss of organelles
- changes in production & destruction of cellular constituents
physiological atrophy
- normal loss of endocrine stimulation
- ex. muscle shrinking with disuse
pathological atrophy
- diminished blood supply, inadequate nutrition, loss of innervation, abnormal loss of endurance stimulation, decreased workload
- ex. skinny legs in fat hyperlipidic person: common iliac artery occluded: loss of blood supply to legs
- brain w focal atrophy from stroke
hypertrophy
- increase in cell size and functional capacity
- due to an increase in the production and number of intracellular organelles (increased metabolic demands on the cell/hormonal stimulation)
physiological hypertrophy
- occurs due to increased functional demand
- ex. muscles getting bigger from working out
pathological hypertrophy
- goiter: hyperactivity of an endocrine gland
- hormone secreting tumor: hyperactivity of an endocrine gland
- excessive demands on an organ: myocardial hypertrophy due to valve damage/hypertension
hyperplasia
increase in the size of an organ or tissue due to an increase in the number of cells (increased functional and/or metabolic demands on the cell or compensatory proliferation)
physiological hyperplasia
- Lactating hormone stimulation > lactating breast
- increase in RBC’s at high altitude
pathological hyperplasia
- endometriosis: higher conc. endometrium
- psoriasis: skin cells have longer cell life>plaque on skin
- liver regeneration following damage
metaplasia
-a change where one terminally differentiated cell type is replaced by another terminally differentiated cell type
reason for metaplasia
response to persistent injury/irritation
most common cell type metaplasia
glandular epithelium is replaced by squamous epithelium
examples metaplasia
- squamous metaplasia: bronchus, bladder
- Barret esophagus: squam > columnar
- Myositis ossificans: blow to soft tissue > lymph doesn’t go away> bone devel. w/in muscle
dysplasia
- disordered growth & maturation of cellular components of a tissue
- loss of uniformity & architectural oreintation of cells
dysplasia is response to
persistent injurious influence and may regress
dysplasia > ?
- dysplasia is a pre-neoplastic lesion
- a necessary stage in the cellular evolution of cancer
cellular adaptations that can give rise to neoplasia
- dysplasia
- hyperplasia
- metaplasia
cellular adaptations that cannot give rise to neoplasia
- atrophy
- hypertrophy
dysplasia: application of CIN grading method
- CIN I: 25% - mild
- CIN II: 50% - moderate
- CIN III: 75% - severe
- 100% : carcinoma in situ or microinvasie carcinoma
3 categories of accumulations of material w/in a cell/organ
- normal cellular constituent
- abnormal substance
- pigment
features of intracellular accumulations
- steatosis
- hydropic change
- pigments
- protein
- glycogen
- cholesterol
steatosis
- accumulation of triglycerides within parenchymal cells
- reversible
- most common organ involved: liver
causes of steatosis
- protein malnutrition
- toxins (alcohol, CCL4 dry cleaning, obesity, anoxia
histological features of steatosis
- peripheralized nucleus
- signet ring structure
hydropic change
- cellular swelling
- increase in H2O accumulation within parenchymal cells
- water accumulation within cytoplasm & cytoplasmic organelles
- reversible
most common cause of hydropic change
-loss of ATP resulting in failure of Na/K ATPase pump > lack of free energy
histological features of hydropic change
swollen cells but centralized nucleus
pigment accumulations
- accumulation of iron within parenchymal cells and within interstitium
- golden brown granules
localized hemosiderosis
- localized/focal pigment accumulations
- common bruise (derived from hemoglobin=RBC breakdown
systemic hemosiderosis
- systemic pigment accumulations
- blood transfusions
- hemolytic anemia (body attacks its own RBCs)
- host vs. graft reaction
- looks like big bruise over entire body
lipofuscin
- undigestable mixture of lipids and proteins thought to be the result of oxidative stress
- increases with age
- “wear and tear pigment”
- type of pigment accumulation
glycogen storage diseases
caused by enzyme deficiency
- Pompe
- McArdle
- Cori
- Von Geirke
Pompe
- glycogen storage disease
- enzyme: acid alpha glucosidase
McArdle
- glycogen storage disease
- enzyme: myophosphorylase
Cori
- glycogen storage disease
- enzyme: debranching enzyme
Von Geirke
- glycogen storage disease
- enzyme: glucose-6-phosphatase
cholesterol accumulation
-can accumulate in macrophages and vascular smooth muscle cells within blood vessel walls: atherosclerosis
xanthomas
- disorders of cholesterol accumulation
- cholesterol gets deposited in random places: under eyes, bones, etc
causes of cell injury
- hypoxia
- physical agents
- chemical agents
- infectious agents
- immunological rxns
- genetic defects
- nutritional imbalances
hypoxia
due to ischemia or decreased O2 carrying capacity of blood
physical agents
trauma, temp, radiation, shock
lack of oxygen causes ?
decrease of synthesis of ATP (so can excess oxygen)
increases in intracellular calcium and loss of calcium homeostasis causes
- activation of Calcium-dependent enzymes
- ex. apoptosis depends on Ca++ release
depletion of ATP causes
loss of membrane function and intracellular processes
defects in membrane permeability causes
cell = like balloon, poke it and it’ll pop
reversible cell injury: subcellular changes
- subcellular changes occur in reversibly injured cells
- cellular swelling: loss of activity of Na/K ATPase pump activity
- steatosis: fatty change: altered metabolism/transport of triglycerides
- REVERSIBLE CAN BECOME IRREVERSIBLE
reversible cell injury: structural cellular changes
- plasma membrane bleb
- increase intracellular volume
- mitochondrial swelling & calcification
- disaggregated ribosomes
- dilated, vesicular endoplasmic reticulum
- aggregated cytoskeletal elements
irreversible injury
- vacuolization of the mitochondria
- rupture of lysosomes (ex. lactate dehydrogenase, creatine kinase)
- nuclear changes
irreversible injury: rupture of lysosomes
- ex. lactate DH, creatine kinase
- shouldn’t have any in blood
- when cells die they perform autolysis and explode then the stuff in them is present in blood when it isn’t normally there
irreversible injury: nuclear changes
- pyknosis: small, shrunken and dark nucleus
- karryorrhexis: fragmented
- karyolysis: faded, nucleus disappears
hypoxic/ischemic injury: reversible
- compromised aerobic respiration
- increased rate of anaerobic glycolysis
- decreased cellular pH
- acute cellular swelling
- detachment of ribosomes from RER
- mitochondrial swelling
hypoxic/ischemic injury: irreversible
- severe mitochondrial vacuolization
- lysosomal membrane rupture/activation of Ca dependent enzymes
- -> cell death “point of no return”
free radical
- a final common pathway in a variety of cell processes
- chemical and radiation injury, cellular agin, oxygen toxicity, microbial killing by phagocytes
- highly reactive, autocatalytic, and unstable
free radical as part of normal metabolism
- everytime you break or make a covalent bond
2. immune response to unknown objects
damage by free radicals
- lipid peroxidation of cell membranes
- oxidative metabolism of cellular proteins
- damage to cellular DNA: > mutations
hydrogen peroxide - H2O2
- free radical
- forms free radicals via Fe catalyzed Fenton reaction
superoxide anion (O2-)
- free radical
- generated by leaks in ETC and some cytosolic reaction
hydroxyl radical (OH)
- free radical
- generated from H2O2 by Fenton rxn
peroxynitrate (ONOO)
- free radical
- formed from NO + O2-
calcification
- deposition of calcium salts (no trabeculae or cortex)
- can be normal or abnormal
pathologic calcification
- abnormal deposition of calcium salts on soft tissues
- types: dystrophic calcification, metastatic calcification
dystrophic calcification
calcium deposition in dead/necrotic or non-viable tissues
metastatic calcification
calcium deposition in normal tissues due to hypercalcemia
necrosis
- morphological changes that occur in cells following cell death in living tissue
- different from apoptosis
necrosis = sum of what 2 processes that follow cell death in living tissue/organs
- denaturation of proteins
2. enzymatic digestion of organelles
hypochlorous acid (HOCl)
- free radical
- produced by macrophages and neutrophils during respiratory burst that accompanies phagocytosis
- dissociates to yield hypochlorite radical (OCl-)
endocrine disturbances that can cause calcification
- PTH secreting tumor: increase blood Ca, decrease renal CA production
- bone tumors: attack bone > release of Ca salts
coagulative necrosis
a pattern of cell death characterized by preservation of cellular outline w/ slow degradation of tissue/cells
liquefactive necrosis
a pattern of cell death characterized by:
- loss of tissue architecture
- cellular debris
- infiltration of WBCs
- ex. brain after stroke, purulent (bacterial/pus infection)
gangrenous necrosis
a pattern of cell death characterized by color change usually due to compromised blood supply
- easily observable
- usually blue, black, green
- ex. nose falls off climbing Everest
caseous necrosis
a pattern of cell death characterized by looking like cheese
-most commonly found with tuberculosis
enzymatic fat necrosis
a pattern of cell death characterized by enzymatic disruption of fat
-ex. pancreas
causes of apoptosis
- embryogenesis
- hormone-dependent involution in adult (ex. breast feeding>back to norm)
- cell deletion in population of cells which have normal turnover
morphological pattern of death by apoptosis
- cell shrinkage
- chromatin condensation
- apoptotic bodies (blebbing)
- phagocytosis of apoptotic bodies by phagocytic cells
features of apoptosis
- considered a natural event: plays imp. role in regulation of normal cell population density
- apoptosis “looks” different than necrosis
- apoptosis may play a role in the pathogenesis of neoplasms (some cells lose ability to become apoptotic: keep growing: fundamental cause of cancer)
heat shock proteins def
-proteins involved in adaptation to stressful/injurious stimuli
heat shock proteins features
- induced and constitutively synthesized
- play an important role in normal cell metabolism
- essential for cell survival in all species subjected to injury
- induced during myocardial and cerebral ischemia
- increased heat shock expression is correlated with attenuation of cell injury/death
HSP 60 & HSP 70
- ex. of heat shock protein
- chaperonins
- involved in protein folding and targeting to final destination
ubiquitin
- ex. of heat shock protein
- facilitates the degradation of proteins
- “surveilance role”: tags proteins to be destroyed not doing their job
