Cell Injury & Adaptive Response Flashcards
symptoms
patient’s subjective observations, usually not quantifiable
signs
abnormalities on physical exam, usually quantifiable
findings
x-rays or results
syndrome
cluster of related symptoms and or signs typically due to a single cause in an individual patient
etiology
the cause of a disease
overly simplistic to think of a disease having a single cause
pathogenesis
sequence of events by which the disease develops
pathognomonic
a particular abnormality is found only in one condition
forme fruste
very mild variant of a more serious disease
incidence
number of new cases per unit time (usually a year)
how is incidence expressed?
“new cases per 100,000 people per year”
prevalence
number of cases at any one time
how is prevalence expressed?
“cases per 100,000 people”
risk
how much your particular situation increases your chance of getting a disease compared with everyone else
diagnosis
name given to the particular disease once identified
prognosis
expected outcome for a particular case of a disease
what influences prognosis?
influenced by diagnosis, the age & general health of the patient, available treatments
what hurts cells?
hypoxia
poor nutrition-cells respond in different ways
infectious agents-several mechanisms depending on agent
immune injury-4-5 types, antibody or t-cell mediated
chemical agents-noxious stuff or too much good stuff
physical agents-trauma, radiation, etc.
what is the prototype for cell injury?
hypoxia
mechanisms of hypoxia
- ischemia
- hypoxemia
- failure of oxidative phosphorylation
ischemia
ischemic hypoxia
lack of arterial blood flow (arterial occlusion, venous occlusion)
pump failure
hypoxemia
hypoxic hypoxia
failure to ventilate or perfuse the lungs
failure of lungs to oxygenate blood
inadequate RBC mass
inability of hemoglobin to carry or release oxygen
failure of oxidative phosphorylation
histotoxic hypoxia
cyanide, carbon monoxide, dinitrophenol
how do different cells tolerate hypoxia?
differently
brain can last 3 minutes without oxygen while leg can last 6 hours
which types of hypoxia can be treated?
ischemia
hypoxemia
we can supply oxygen ut we cannot make cells use it
hypoxic injury
- lack of O2 stops oxidative phosphorylation/ETC
- Na/K ATPase fails - Na and H2O enter cell-acute cellular edema
- early sign of cell injury - anaerobic metabolism leads to lactic acid accumulation and pH drop
- denatures proteins - Ca ATPase fails
- Ca enters cytoplasm from ECF and ER
- Transition from reversible to irreversible injury - Ca entry is key step leading to cell death
- rigor mortis due to Ca-induced sarcomere shortening
Ca entry steps leading to cell death
activates phospholipases that damage membranes
activates proteases that destroy proteins
activates endonucleases that destroy DNA
opens pores in outer mitochondrial membrane
-shuts down oxidative phosphorylation
-mitochondria release free radicals
-mitochondria release capsases that induce apoptosis
free radical injury mechanisms
common mechanism of cell injury
-radiation, poisons, normal metabolism
free radical injury cause
unpaired electron in outer (valence) orbital, typicall O2 derivatives
-superoxide (O2), hydroxyl (OH), hydrogen peroxide (H2O2)
free radical injury effects
damage cell membranes
cause DNA mutations
aging
how to combat limited ability to dispose of free radicals
superoxide dismutase and catalase
antioxidants-vitamin e, vitamin c
chemical injury mechanism
depends on nature of poison
- acids/alkalis destroy membranes
- formalehyde crosslinks proteins and DNA
other poison examples
cyanide-blocks ETC mushrooms (toadstools)-destroy ribosomes chemotherapy-damages DNA strychnine-motor neuron synapses carbon monoxide-replaces O2 on hemoglobin, blocks ETC
cellular accumulations/deposits
can indicate cellular injury or systemic disease
- triglycerides (fatty change, steatosis)
- glycogen
- complex lipids or carbohydrates
- pigments
- calcium
what organs do fatty changes involve?
liver
heart
what do fatty changes indicate?
not injurious to cells but marker for injury
what are fatty changes linked to?
heavy drinking obesity and metabolic syndrome -non-alcoholic steatohepatitis (NASH) malnutrition/hyperalimentation outdated tetracycline ileal bypass for weight reduction
hyperalimentation
feeding by vein
fatty change mechanisms
too much free fat coming to the liver
too much fatty acid synthesis by the liver
impaired fatty acid oxidation by liver
excess esterification of fatty acid to triglycerides by liver
too little apoprotein synthesis by liver
failure of lipoprotein secretion by liver
glycogen/other lipids or polysaccharides storage diseases
infusions of glucose (dextrose)
inborn errors of metabolism
cannot be broken down, builds back up
pigments-carbon
smoke and soot
engulfed by macrophages
lungs-anthracosis
inert, ugly
pigments-lipofuscin
remnants of intracellular membranes damaged by free radicals indicator of oxidative stress wear and tear pigment inert seen in hard working organs-liver, heart
pigments-melanin
present in melanocytes and their tumors (melanomas)
eumelanin
protects from UV light
pheomelanin
generates free radicals on UV exposure
redheads
albinos
do not produce melanin
hyperpigmentation
increased ACTH-increased production of melanin
hemochromatosis
do not break down melanin adequately
pigments-bilirubin
yellow-orange product of hemoglobin breakdown conjugated by live and excreted by bile elevated levels produce jaundice-check nailbeds and sclera multiple causes
pigments-jaundice
too many red cells being broken down
-hemolytic processes (sickle cell, thalassemias, pernicious anemia)
liver can’t conjugate bilirubin fast enough
example conditions that cause jaundice
liver cannot conjugate bilirubin fast enough:
liver disease
newborn “physiologic jaundice of the newborn”
breast feeding (first few weeks)
hereditary defects (Gilbert’s non-disease, Crigler-Najjar)
biliary obstruction:
gallstones, pancreatic cancer
pigments-calcium
calcium phosphate, calcium hydroxide buildup
dystrophic calcification
occurs with normal calcium metabolism
examples of normal dystrophic calcification
pineal gland, airway cartilages, mitral valve annulus, aortic valve sinuses-can lead to aortic stenosis
examples of abnormal dystrophic calcification
breast cancers, caseous necrosis of TB, surgical scars, pancreatic necrosis-intractable pain, retained abortions-“lithopedion”
results of abnormal calcium metabolism
metastatic calcification
- occurs with high calcium and/or phosphate levels
- indicators of disease causing increased ca/phos
calcium precipitation-pH gradients
sites of pH gradients make precipitation of ca and phos more likely to occur
small airway walls, gastric fundus epithelium, renal tubular walls
necrosis
gross and microscopic changes that indicate cell death
types of necrosis
coagulation
liquefactive
caseous
apoptosis
coagulation necrosis
usually due to ischemic hypoxia or free radical injury
death of groups of cells
gross characteristics of coagulation necrosis
soft, pale
micro characteristics of coagulation necrosis
loss of nuclei but cytoplasm intact
coagulation necrosis response
dead cells product acute inflammatory response
may be replaced by scar, destroyed, walled-off, infected, or even heal
liquefaction necrosis
usually due to bacterial infections or poisons or ischemic hypoxia in CNS
death of groups of cells
what causes liquefaction necrosis?
hydrolysis via lysosomal or WBC enzymes “pus”
gross characteristics of liquefaction necrosis
gelatinous mass or nothing there
caseous necrosis
aka saponification (soap formation)
usually due to immune injury in response to certain infections (TB, fungus)
deaths of groups of cells
midpoint between coagulation and liquefaction
gross characteristics of caseous necrosis
crumbled, friable devris
pale, cheesy
terms for apoptosis
programmed cell death
cell suicide
physiologic way for cell to die
two triggers for apoptosis
mitochondrial damage-leak enzymes called caspases (Ca2 entry can cause this)
death receptor-Fas (CD95) or TNF receptors bind their ligands
examples of apoptosis
embryologic remodeling of hands breast shrinkage after lactation period cells in outer layers of epidermis neurons that don't synapse killing of virally-infected cells
what causes apoptosis?
usually due to immune response or in response of cellular damage
what happens with apoptosis?
death of single cell
cell membrane remains intact-no leakage of cell contents
no inflammatory response
remains phagocytized by microphages
gangrene
advanced and grossly visible necrosis
mostly coagulation gangrene
“dry” gangrene
usually no infection
mostly liquefactive gangrene
“wet” gangrene
foul-smelling
infected
types of bacterial gangrene
clostridial “gas” gangrene
trench mouth
fournier’s gangrene
clostridial gangrene
flesh eating bacteria that produce cell membrane disrupting toxin
trench mouth
bacterial gangrene caused by malnutrition
fournier’s gangrene
scrotal necrosis
living cell adaptations
changes in response to stress or injury or lack of normal stimulation
what happens if cells are effective with adaptations?
mitigate injurious agent
what happens if cells are ineffective with adaptations?
cell death
what triggers cell adaptations?
reversible alterations in gene activity
atrophy
decrease in cell size may result in decreased organ size
reversible, usually
fewer organelles and decreased function, some may die
causes of atrophy
loss of motor innervation decreased blood supply loss of hormonal stimulation malnutrition aging
examples of atrophy
loss of breast tissue after menopause
loss of muscle mass inside a cast
shrinkage of kidney with arterial disease
misnomers of atrophy
not cell loss, but decrease in cell size
hypertrophy
increase in cell size, may result in increased organ size
cells have increased protein synthesis, increased organelles
causes of hypertrophy
increased workload
increased hormonal stimulation
examples of hypertrophy
skeletal muscle of strength athlete
heart of obese person
heart of hypertensive person
smooth muscle of uterus in pregnancy
misnomers of hypertrophy
BPH
calluses
heart hypertrophy can be _______or ______
physiologic
pathologic
hyperplasia
increase in cell number, may result in increased organ size
generally reversible with stimulatory agent
genetic mutations will not reverse
hyperplasia may be _________ or ________
physiologic
pathologic
causes of hyperplasia
compensatory-“growing back”
hormonal stimulation
genetic mutations-risk for cancer
examples of hyperplasia
female breast at puberty endometrium during menstrual cycle lymph nodes close to infection adrenal cortex under "stress" bone marrow after blood donation gingival tissue in people on phenytoin (Dilantin)
metaplasia
adaptive substitution of one cell type for another
theoretically reversible
often involves epithelium in response to a stimulus
certain metaplasias due to gene mutations-they won’t reverse
examples of metaplasia
columnar to stratified squamous epithelium in gallbladder with stones
columnar to stratified squamous epithelium in cervix of women with HPV
stratified squamous to columnar epithelium in esophagus of people with chronic reflux (Barrett’s)
is it really adaptive?
dysplasia
bad growth, atypia, atypical hyperplasia
used in reference to epithelium
loss of cell uniformity and orientation
is dysplasia cancer?
no, they resemble cancer cells but are not invasive
what causes dysplasia?
genetic mutations that create a growth advantage
anaplasia
nuclear changes
what promotes dysplastic process?
ongoing epithelial injury promotes dysplastic process
bronchi of smokers
cervix of HPV-infected women
reflux of acid into esophagus
what is really ugly anaplasia
carcinoma in situ
what happens with bizarre cells obtain blood supply?
form a mass, neoplasia
neoplasia
new growth
what do anaplasia cells look like and what are they capable of?
ugly cells; can be:
- dysplasia-confined to an epithelium OR
- cancer-invading
what is dysplasia in terms of types of cells?
precancerous anaplastic cells confined to an epithelium and not invading, not neoplasm
what is neoplasm with anaplasia?
malignant (cancer)
will invade and spread
what if neoplasm does not exhibit anaplasia?
it is benign, not cancer
may compress surrounding structures but will not invade or spread
what mediates atrophy, hypertrophy, hyperplasia and metaplasia?
normal growth and differentiation genes
proto-oncogenes
proto-oncogenes
normal gene
what mediates dysplasia and cancer?
same growth and differentiation genes that now function abnormally
oncogenes
oncogenes
loss of cell regulation
