-
Pathology
study of funcitonal and structural changes in cells, tissues and organs that underlie disease
-
four core aspects of pathology
- etiology=cause
- pathogenesis=mechanisms of development
- morphological changes=structural alterations of cells and organs
- clinical significance=functional causes of morphological changes
-
name four types of cell adaptation
- hyperplasia
- hypertrophy
- atrophy
- metaplasia
-
when does cell adaptation occur?
response to increased demand, decreased demand, or chronic irritation
-
hyperplasia
increased NUMBER of cells
occurs if cells have ability to replicate i.e. mucosa of gastrointestinal tract
-
hypertrophy
increased SIZE of cells
less regenerative capacity, so get bigger instead of replicating, i.e. heart muscle
-
do uterine cells undergo hypertrophy or hyperplasia to meet the demands of pregnancy?
Both
-
atrophy
diminuation in size
-
Some reasons cells atrophy (7)
- decreased workload
- loss of innervation
- diminished blood supply
- inadequate nutrition
- loss of endocrine stimulation
- aging
- pressure
-
metaplasia
one adult cell types is replaced by another
usually occurs in epithelial tissue as a result of chronic irritation
-
reversible cell injury
cell has potential to return to function of harmful stimulus is withdrawn
-
irreversible cell injury
leads to cell death by necrosis or apoptosis
-
stimuli that cause cell injury (6)
- oxygen deprivation
- physical agents
- chemical agents
- infection agents
- genetic derangements
- nutritional imbalances
-
hypoxia
insufficient oxygen in blood stream
-
ischemia
insufficient blood supply
-
Why is ischemia often more damaging to cells than hypoxia?
B/c not only is there too little oxygen, but there is also too little nutrients and no removal of wastes
-
examples of physical agents (5)
- mechanical injury
- temperature
- barometric pressure
- radiation
- electric shock
-
example of problem with protein production
alpha-thalassemmia where one hemoglobin molecule is not produced and the oxygen carrying capacity of the blood is compromised
-
example of protein function that cause cell injury
sickle cell anemia where hemoglobin molecules are structurally unstable
-
Tay-Sachs
enzyme needed for removal of waste products is missing
-
Name 5 essential strutures or functions of the cell
- 1. generation of ATP by mitochondria
- 2. Integrity of mitochondria
- 3. Transmembrane calcium homeostasis
- 4. Protection against oxidative stress
- 5. Membrane impermeability
-
What happens when ATP production is reduced by just 5-10%?
- -Na+/K+ pump compromised
- -switch to anaerobic metabolism -->Accumulation of "H+ so lower pH
- -influx of Ca++ from extracellular space
- -dissolution of protein synthesis apparatus
-
What happens when there is damage to electron transport chain resulting in less ATP?
proton motive force of inner mitochondrial membrane disrupted
Cytochorme c leaks out fo inner mitochondrial membrane, promoting apoptosis
-
What happens with calcium when there is cell injury?
More calcium enters permeable membranes of cell. Increase in cytosolic calcium activates enzymes that cuases cells to eat themselves inside out.
-
free radical
molecule with an unpaired electron in its outer orbit
e.g. hydroxl (OH), hydrogen pyroxide (H2O2), superoxide anion (O2-) nitric oxide (NO)
-
What can happen when free radicals react with other molecules?
- lipid peroxidation (disruption)
- denatured proteins
- breaks in DNA
free radicals produce more free radicals, increasing oxidative stress of cell
-
antioxidant
scavenge free radicals
-
Two changes that characterize irreversible injury include
mitochondrial function cannot be restored
membrane integrity cannot be restored
-
list morphological features of cell injury (4)
- mitocondrial swelling
- alterations of plasma membrane
- dilaion of the ER, with dissociation of ribosomes
- nuclear changes
-
if cell injury persists beyond a few hours
cellular swelling due to loss of ability to maintain electrolyte balance
hydropic change = vacuolar degeneration - ER swollen
-
two morphological patterns of cell death
necrosis = cell death due to secondary, exogenous injury
apoptosis = programmed cell death
-
What happens with necrosis?
tissue distruction by endogenous enzymes from either leaky lysosomes or inflammatory cells
"soup"
-
types of necrosis (4)
- 1. coagulative (ischmic injury)outline of cells remain but intracellular detail lost "mummified"
- 2. liquefactive inflammatory cells digest tissue creating pus made of cellular debris. Common in bacterial and fungal infections
- 3. caseous found inside a granuloma (inflammatory response to certain fungi or mycobacteria) contains pus adn organism. Thick, white and cheesy.
- 4. Fat - death fo fat cells. Can be coagulative r liquefactive
-
dystrophic calcification
formation of calcium crystals in areas of necrosis
calcium binds with phospholipids present in fragments of degenerated or dying cells.
typical in atheroschlerosis and pancreatitis
-
apoptosis
Programmed cell death - cell in induced to dismantle itself
Plasma membrane stay intact so there is no destruction of surrounding tissue or initiation of inflammatory response
-
How are apoptopic cells cleared from system
phagocytes recognize symbols on cell membranes
-
What is the most powerful stimulus for apoptosis?
irreparable damage to DNA by radiation or chemo
-
stimuli that can cause apoptosis
- viral disease
- oxidative damage
- heat
- hypoxia
- cytotoxic T lymphosite
-
end result of apoptosis
production of caspases, enzymes that digest the cytoskeleton and activate enzymes that digest the intracellular contents
plasma membrane creates pockets of cellular contents which are engulfed by phagocytes
plasma membrane NOT broken down so no inflammatory response
-
common cellular accumulations
- lipofuscin - lipid accumulation due to free radical injury
- hemosiderin - iron in cell cytoplasm
- protein - chronic diseases of the kidney can cause accumulation in proximal tubules
- fat-in hepatocytes due to impairment of liver cells to metabolize fatty acids
-
areas of inflammation and needle shaped clear spaces are ...
the footprint of cholesterol derived from cell membranes during necrosis
|
|
