Pathology Flashcards
define “signs” of abnormal clinical findings, and what are some examples
- something that can be detected by a clinician even if patient is unconscious
- swelling
- redness
- fever
define “symptoms” and what are some examples
- something that the patient must tell you
- chest pain
- SOB
- nausea
- HA
some underlying etiology causes cell damage, which leads to tissue changes and then pathogenesis. At which point in this process could changes be detected through testing?
at the level of tissue change, morphologic changes can be seen on biopsy and molecular changes can be detected in blood
hypertorophy
increase in cell size due to increase in stress
hyperplasia
increase in number of cells due to increase in stress
mechanism of hypertrophy
gene activation, protein synthesis and production of organelles
mechanism of hyperplasia
proliferation of mature cells and in some cases, increased output of new cells from stem cells
hyperplasia and hypertrophy often occur together (eg uterus during pregnancy). What is an exception to this rule
permanent tissues cannot undergo hyperplasia and therefore will only undergo hypertrophy
•cardiac muscle, skeletal muscle, nerve
uterus hypertrophy/hyperplasia during pregnancy is an example of a physiologic process. Contrast this with pathologic hyperplasia
eg endometrial hyperplasia
in the pathologic process, hyperplasia can progress to dysplasia and eventually cancer
benign prostatic hyperplasia (BPH) is a pathologic process, but is unique in that
unlike other pathologic hyperplasia, it does not increase the risk of prostate cancer
atrophy
decrease in number and size of cells due to a decrease in stress
mechanism of decreased number of cells in atrophy
apoptosis and autophagy
metaplasia
a change in cell type due to a change in stress on an organ
most common cell types involved in metaplasia
one type of surface epithelium to another (squamous, cuboidal, columnar)
mechanism of metaplasia
reversible reprogramming of stem cells -> production of new cell type
dysplasia
disordered cellular growth, most often refers to proliferation of precancerous cells
dysplasia often arises from longstanding pathologic ___ or ___
hyperplasia or metaplasia
dysplasia is reversible with alleviation of inciting stress. If stress persists however, it progresses to
carcinoma, which is irreversible
aplasia
failure of cell production during embryogenesis (eg unilateral renal agenesis)
hypoplasia
decrease in cell production during embryogenesis, resulting in relatively small organ (ie streak ovary in turner syndrome)
what is a common cause of pathologic hyperplasia
excessive or inappropriate actions of hormone or growth factors
mechanism of decreased size of cells in atrophy
- protein synthesis decreased b/c reduced metabolic or nervous activity
- ubiquitin-proteosome degradation of cytoskeleton and autophagy of cellular components
what are 2 features of reversible cell injury that can be recognized under light microscopy?
cellular swelling and fatty change
when does cellular swelling occur
•when cells are incapable of maintaining ionic and fluid homeostasis
cause of cellular swelling
- failure of energy-depending ion pumps in plasma membrane
* ie decreased ATP -> decreased Na/K pump activity
when does fatty change occur
hypoxic injury and various forms of toxic or metabolic injury
what cells is fatty change usually seen in
- cells involved in and dependent on fat metabolism
* ie hepatocytes and myocardial cells
ATP depletion is a mechanism of cell injury. What happens here?
failure of energy-dependent functions -> reversible injury -> necrosis
Mitochondrial damage is a mechanism of cell injury. What happens here?
ATP depletions -> failure of energy-dependent fxns -> ultimately necrosis; under some conditions leakage of mitochondrial proteins can trigger apoptosis
Influx of calcium is a mechanism of cell injury. What happens here?
activation of enzymes that damage cellular components and may also trigger apoptosis
accumulation of reactive oxygen species is a mechanism of cell injury. What happens here?
covalent modification of cellular proteins, lipids, nucleic acids
increased permeability of cellular membranes is a mechanism of cell injury. What happens here?
may affect plasma membrane, lysosomal membranes, mitochondrial membranes -> typically causes necrosis
accumulation of damaged DNA and misfolded proteins is a mechanism of cell injury. What happens here?
triggers apoptosis
morphologic appearance of necrosis is the result of
denaturation of intracellular proteins and enzymatic digestion
what happens in irreversible cell injury (cell death)?
- karyolysis
- pump failure, leakage of enzymes
- profound disturbances in membrane function
what happens to the cytoplasm (histologically) in cell death
- becomes more eosinophilic
* loss of basophilia that was normally imparted by the RNA in cytoplasm
what is karyolysis
- breakdown of nucleus due to DNase activity
* basophilia of chromatin fades
What is pyknosis
nuclear shrinkage -> increased basophilia
what is karyorrhexis
when the DNA condenses into a solid shrunken mass
most common kind of necrosis is
coagulative, liquefactive may be second
coagulative necrosis can occur in all organs except what
the brain
histologic appearance of coagulative necrosis
eosinophilic, anucleate cells may persist for days to weeks, then ultimately removed by phagocytosis
what is a localized area of coagulative necrosis called?
infarct
where does liquefactive necrosis predominantly occur?
brain/CNS
hypoxic death of cells within CNS often manifests as
liquefactive necrosis
what is liquefactive necrosis characterized by
- digestion of dead cells -> transformation of tissue into liquid viscous mass
- necrotic material often creamy yellow because of dead leukocytes (pus)
where does fat necrosis commonly occur
in the peripancreatic fat due to release of activated pancreatic lipases into pancreas and peritoneal cavity
histologic appearance of fat necrosis
foci of shadowy outlines of necrotic fat cells with basophilic calcium deposits, surrounded by an inflammatory reaction (foamy macrophages)
what is a common site of caseous necrosis
lung
what is usually the underlying cause of caseous necrosis
infection with mycobacterium (ie TB) or fungal infections
histologic appearance of caseous necrosis
- necrotic area appears as a structureless collection of fragmented or lysed cells and amorphous granular debris enclosed w/in a distinctive inflammatory border -> granuloma
- key is presence of multinucleated cells
where does fibrinoid necrosis occur
in blood vessels
what typically causes fibrinoid necrosis
deposition of antigen-antibody complexes in walls of arteries
histologic appearance of fibrinoid necrosis
deposits of “immune complexes” with fibrin that has leaked out of vessels -> bright pink and amorphous appearance in HandE stains
what is dry gangrene
common in lower limbs of diabetics. it is histologically a coagulative necrosis
what is wet gangrene
necrosis caused by loss of blood supply (coagulative) with a concurrent bacterial infection causing pus formation (liquefactive)
*not as common as dry gangrene
what is apoptosis
a regulated mechanism of cell death -> eliminated unwanted and irreparably damaged cells with LEAST possible host reaction
apoptosis is characterized by enzymatic degradation of proteins and DNA followed by recognition and removal of dead cells by phagocytes. What initiates it
caspases
what are the 2 major pathways of apoptosis
- mitochondrial pathway (INTRINSIC)
* death receptor pathway (EXTRINSIC)
physiologic apoptosis, such as that which occurs in embryogenesis follows which pathway
intrinsic (mitochondrial) pathway
examples of physiologic apoptosis
- embryogenesis
- involution (endometrium, lactating breast, thymus)
- proliferating populations (intestinal crypts)
examples of pathologic apoptosis
- DNA damage (chemotherapy)
- misfolded proteins (neurodegenerative disease)
- infections (viral)
- pathologic atrophy in parenchymal organs after duct obstruction, such as occurs in pancreas, parotid gland, and kidney
contrast cell size in necrosis and apoptosis
- in necrosis, cells become enlarged -> burst
* in apoptosis cells shrink
contrast what happens to the nuclei in necrosis and apoptosis
- necrosis: pyknosis -> karyorrhexis -> karyolysis
* apoptosis: cut into nucleosome-sized fragments
contrast what happens to plasma membranes in necrosis and apoptosis
- necrosis: membranes disrupted
* apoptosis: intact; but altered structure, esp. orientation of lipids
contrast adjacent inflammation in necrosis and apoptosis
- necrosis: frequent adjacent inflammation
* apoptosis: never
Ca2+ is normally mainly extracellular. If some injurious agent allows excessive Ca2+ influx cellular enzymes can be activated that cause cellular damage. What types of damage can increased cytosolic Ca2+ cause
- phosopholipase and proteases can lead to MEMBRANE DAMAGE
- endonucleases can lead to NUCLEAR DAMAGE
- INCREASED MITOCHONDRIAL PERMEABILITY -> DECREASED ATP
Autophagy is a survival mechanism in times of nutrient deprivation; starved cell eats its own contents and recycles -> provided nutrients and energy. What is the process of autophagy
lysosomal digestion of cell’s own components
bulk autophagy is nonselective, and can be contrasted with selective autophagy, which involved
ubiquitin tagging
atuophagy is involved in the clearance of _____.
Therefore defective autophagy may a cause of _____
misfolded proteins; neuronal death induced by accumulation of the misfolded proteins -> neurodegenerative disease
3 major causes of hypoxia
- ischemia
- hypoxemia
- decreased O2 carrying capacity of blood
what is saponification?
- occurs when fatty acids released by trauma or lipase join with calcium
- this is part of the process of fat necrosis
caspaces are the mediators of apoptosis. What do they do?
- activate proteases (break down cytoskeleton)
* activate endonucleases (break down DNA)
what is the key mediator of the intrinsic (mitochondrial) pathway of apoptosis?
cytochrome C (which is located in the mitochondrial membrane)
