study of disease processes over time; a series of sequential stages from normal to abnormal
the cause of the disease; the initiating event or insulting agent and its related risk factors
mechanisms involved in the transition from normal to abnormal
clinical expression of the disease
signs and symptoms due to cell injury
An individual arrives at the ER with chest pain, shortness of breath, and he dies shortly after being admitted. After examining prior medical records it was noted that he had chronically high cholesterol and blood pressure. Upon autopsy it was determined his death was due to myocardial infarction due to a clot in his coronary arteries caused by plaque build up. What was this pts: etiology, clinical expression of disease and pathogenesis
Clinical expression: chest pain, SOB, death Etiology: high cholesterol, high BP Pathogenesis: plaque buildup in the artery and subsequent clot
in general, when is cell injury reversible? irreversible?
reversible: mild/transient injurious stimulus irreversible: severe and/or progressive injurious stimulus
what are some ways cells can adapt to stress?
changes in cell size, cell number, cell type/differentiation
what is hypertrophy?
increase in cell size
what is hyperplasia?
increase in cell number
How do cells increase in size?
increased gene activation, protein and organelle synthesis
how to cells increase in number?
more/new cells produced from stem cells
When do we see hyperplasia and hypertrophy occurring together? give an example?
in general, hyperplasia and hypertrophy occur together. Ex: the uterus during pregnancy
when do we see hypertrophy but NOT hyperplasia? give examples (2)
when cells are able to grow but not divide. this occurs in skeletal muscle cells and cardiac muscle cells
what is aplasia?
failure of cell division during embryogenesis (the cells are not there)
what is hypoplasia?
decrease in cell production during embryogenesis; resulting in small organ/tissues
what is atrophy?
decrease in size of a tissue/organ due to a decrease in cell size (degradation pathways) or cell number (apoptosis)
A decrease in cell size can be accomplished by which degradation pathways?
ubiquitin-proteasome pathway, autophagy (microautophagy, macroautophagy, chaperone-mediated auotphagy)
contrast the ubiquitin-proteasome pathway and the autophagy pathway?
UP: requires ATP, specific, mostly degrades short-lived/damaged proteins (gene expression, differentiation), and cytoskeleton (IF) A: activated by cell stress. degrades proteins and organelles. can be selective or non-selective.
what is metaplasia
an alteration in cell type as a result of a chang ein environment/stress
which disease is "high yield" for metaplasia. cause?
Barrett's esophagus. cells in esophagus change from stratified squamous epithelium to simple columnar mucus producing epithelium to better cope with reflux of stomach acid into esophagus
what is dysplasia
disordered cell growth; can progress to cancer if stimulus persists
In general, epithelial cells that are located closer to BM proliferate/differentiate and cells that are more apical (towards lumen) proliferate/differentiate
closer to BM=proliferate closer to lumen=differentiate, even lose their nucleus!
what is the morphologic hallmark of cell death? how can this occur (3)
loss of nucleus that occurs via nuclear condensation, nuclear fragmentation, nuclear dissolution
nuclear condensation (small dark nucleus)
nuclear dissolution (absent nucleus)
cell death can occur in what two ways?
necrosis and apoptosis
necrosis is generally correlated with what type of nuclear loss
apoptosis is generally correlated with what type of nuclear loss (2)
do normal cells undergo necrosis?
no, necrosis is pathologic (related to a disease state) NOT physiologic
what are the six types of necrosis
coagulative, liquefactive, gangrenous, caseous, fat, fibrinoid
what is coagulative necrosis. commonly seen where?
the organ/cell shape is preserved and the nucleus is absent. typical of ischemic infarction of any organ (except brain)
what is liquefactive necrosis? seen?
necrotic tissue is liquified by enzymes. Seen in brain, pancreas, abcess
what is ischemia?
restriction in blood supply
what is gangrenous necrosis?
coagulative necrosis becomes mummified (dry) and may get secondarily infected and liquefactive necrosis results
what is caseous necrosis? seen?
cheese-like combination of liquefactive and coagulative necrosis. seen in TB (lungs)
what is fat necrosis. seen?
tissue becomes chalky white due to calcium deposition. seen in breast trauma and pancreatitis
what is fibrinoid necrosis
necrosis of blood vessel wall
genetically programmed, ATP dependent cell death
which type of cell death is accompanied by inflammation?
necrosis. NOT apoptosis
what types of things can injure cells? 7
1. Oxygen deprivation 2.chemicals/drugs 3. physical injury 4. infectious agents 5. immune response 6. nutritional imbalance 7. genetic derangement
what is the function unit of the liver?
describe the anatomy of a liver lobule
Hepatic Artery (oxygenated) drains into portal vein. Portal vein drains into central vein via hepatic sinusoids. Bile duct drains into duodenum (opposite direction of blood flow)
what are the three hepatocyte zones between the portal vein and central vein
closest to PV: Zone 1, Zone 2, Zone 3 (closest to CV)
which hepatocyte zone has hepatocytes that receive the most oxygen? why?
the zone 1 hepatocytes because they are closest to the protal vein (which is a mix of oxygenated arterial blood and deoxygenated blood from gut)
which zone contains more gluconeogenesis and FA oxidation enzymes?
Zone 1 (closest to PV)
which zone contains more Cytochrome P450 enzymes, glycolytic enzymes, and FA synthesizing enzymes?
Zone 3 (closest to CV)
Acetaminophen excess causes necrosis of which zone hepatocytes? why?
Zone 3. the detox of Acetaminophen produces free radicals that cause necrosis. this is an example of a chemical injury to cells.
anoxia generally causes ___ while hypoxia generally causes ___
anoxia: cell death (necrosis) hypoxia: atrophy
what are 3 conditions related to chemical/drug injury:
1. Gynecomastia: enlarged breasts in males (imbalance of hormones that can be caused by heroin, statins) 2. Gingival Hyperplasia: gums take-over the teeth (phenytoin, used to control seizures) 3. Cirrhosis of the liver; many casues including alcohol
what are some examples of physical injury to cells?
burns, frostbite, laceration
what are some examples of infectious agents causing injury to cells?
what are some examples of immune response causing injury to cells?
what are some examples of nutritional imbalances causing injury to cells? 4
Vit A defic, Marasmus, Kwashiorkor, obesity
Marasmus: cause? appearance
protein-calorie defic. wasted appearance
Kwashiorkor: cause? appearance?
severe protein defic. distended abdomen
a cell undergoes chronic stress, but it is of low intensity, what is the likely outcome?
a cell undergoes acute high intensity stress, what is the likely outcome?
a cell undergoes acute low intensity stress, what is the likely outcome?
reversible cell injury
describe cells as hyperplasia, dysplasia, normal, cancer
L to R: Normal, Hyperplasia, Dysplasia, Cancer
Note the concentrated maintatined nucleus in dysplasia
label the zones, what is this?
L to R: Zone 1, Zone 2, Zone 3
Marasmus: protein-calorie defic
Kwashiorkor: severe protein defic