Study your flashcards anywhere!

Download the official Cram app for free >

  • Shuffle
    Toggle On
    Toggle Off
  • Alphabetize
    Toggle On
    Toggle Off
  • Front First
    Toggle On
    Toggle Off
  • Both Sides
    Toggle On
    Toggle Off
  • Read
    Toggle On
    Toggle Off

How to study your flashcards.

Right/Left arrow keys: Navigate between flashcards.right arrow keyleft arrow key

Up/Down arrow keys: Flip the card between the front and back.down keyup key

H key: Show hint (3rd side).h key

A key: Read text to speech.a key


Play button


Play button




Click to flip

73 Cards in this Set

  • Front
  • Back
- failure of cell production
- during development, aplasia results in agenesis
- later in life, can be caused by permanent loss of precursor cells (e.g. bone marrow)
- absence of an organ due to failure of production
- decrease in cell production, that is less extreme than seen in aplasia
- e.g. partial lack of growth and maturation in gonadal structures in Turner and Klinefelter's syndromes
what causes atrophy?
- disuse
- nutritional or O2 deprivation
- diminished endocrine stimulation
- aging
- denervation
what is characteristic of atrophy?
- presence of autophagic granules- intracytoplasmic vacules with debris from degraded organelles
- replacement of one tissue type with another
1. squamous metaplasia
2. ossseous metaplasia
3. myeloid metaplasia
squamous metaplasia
- cervix: replacement of columnar epithelim with squamous cells at the quamocolumnar junction
- also found in the:
bronchus epithelium
pancreatic ducts
what is squamous metaplasia caused by?
- chronic irritation (e.g. tobacco use)
- vit A deficiency
is squamous metaplasia reversible?
- yes
osseous metaplasia
- formation of new bone at sites of injury
- cartilaginous metaplasia can also be seen
myeloid metaplasia
- aka extramedullary hematopoiesis
- proliferatino of hematopoietic tissue at sites other than the bone marrow (e.g liver and spleen)
define anoxia
complete lack of O2 to tissues
define hypoxia
reduced O2 to tissues
what causes hypoxic/anoxic cellular injury?
- ischemia (most common cause)
- anemia
- CO poisoning
- decreased perfusion by O2 carrying blood (seen in heart failure, hypotension, shock)
- poor oxygenatin of blood secondary to pulmonary disease
what organelle does hypoxic cell injury first affect?
mitochondria -> decreased oxidative phosphorylation -> decreased ATP synthesis
what are some consequences of low ATP? (Early stage)
1. failure of the cell membrane pump -> swelling of cell and organelles
2. disaggregation of ribosomes -> failure of protein synthesis
3. stimulation of phosphofructokinase activity -> increased glycolysis, accumulation of lactate, and decreased intracellular pH
what happens when you inhibit the Na-K-ATPase pump?
1. cellular swelling (hydropic change)-> see large vacuoules in the cytoplasm
2. swelling of the ER -> one of the first ultrastructural changes that you can see
3. swelling of mit -> dilation of inner mit space (eventually becomes irreversible)
what is hydropic change?
cellular swelling
what is ribosomal disaggregation caused by?
- decreased ATP levels
- and membrane damage
what does low pH within a cell lead to?
- reversible clumping of nuclear chromatin
- results from the increased activity of phosphofructokinase as seen in hypoxic injury
what are some consequences of low ATP? (Late stage)
- eventually leads to membrane damage -> loss of membrane phospholipids
- will see myelin fingers
- cell blebs
myelin fingers
- whorl like hings coming from damaged membranes
- seen in late stage hypoxic injury
cell blebs
- cell surface deformity caused by dysfunctional cellular cytoskeleton
what is the point of no return, where cell death is gauranteed?
- when you get irreversible damage to the cell membranes
- massive Ca influx
- extensive calcification of mit
name enzymes in serum that indicate a previous MI
1. AST (aspartate aminotransferase; previous aka SGOT)
2. Lactate dehydrogenase (LDH)
3. Creatine kinase (CK, or CPK)
4. Troponin I & T
5. myoglobin
name serum enzymes that indicate liver dysfunction
1. AST
2. alanine aminotransferase (ALT)
3. alkaline phosphatase
4. gamma- glutamyltransferase (GGT)
give time line of reversibility for hypoxic injury
3-5 minutes for neurons
1-2 hours for myocardial cells and hepatocytes
many hours for skeletal muscles
which neurons are most susceptible to hypoxic injury?
- purkinje cells of the cerebellum
- neurons of the hippocampus
examples of free radicals
- superoxide (O2-)
- hydroxyl (OH)
what generates free radicals?
1. normal metabolism
2. oxygen toxicity
3. ionizing radiation
4. UV light
5. Drugs and chemicals
6. Reperfusion injury
Criteria for ARDS
* Acute onset
* Bilateral infiltrates on chest radiograph
* Pulmonary artery wedge pressure < 18 mmHg
* if PaO2:FiO2 < 300 mmHg acute lung injury (ALI) is considered to be present
* if PaO2:FiO2 < 200 mmHg acute respiratory distress syndrome (ARDS) is considered to be present
where do you see oxygen toxicity?
- alveolar damage that can cause ARDS
- retrolental fibroplasia (retinopathy of prematurity) -> leads to blindness in infants
how do drugs and chemicals cause free radical toxicity?
- many promote both
1. proliferation of the smooth ER
2. and inductin of the P-450 system of mixed function oxidases of the SER
what are the signs of barbiturate intoxication?
- proliferation and hypertrophy of the SER hepatocyte
How do you degrade free radicals?
- intracellular enzymes (glutathione peroxidase, catalase, SOD)
- antioxidants (vit A, C, E, cysteine, glutathione, selenium, ceruloplasmin, transferrin
- spontaneous decay
list the intracellular enzymes that degrade free radicals
- glutathione peroxidase
- catalase
list exogenous and endogenous antioxidants
- vit A, C, E
- cysteine
- glutathione
- selenium
- ceruloplasmin
- transferrin
describe toxicity by carbon tetracholoride (CCL4)
- CCl4 is processed by the P-450 system -> highly reactive free radical CCL3 -> CCl3 diffuses across cell initiating lipid peroxidation of intracellular membranes.
1. disaggregation of ribosomes
2. Plasma membrane damage
During chemical cell injury, elaborate on the disaggregation of ribosomes
- decreased protein synthesis
- accumulation of intracellular lipids (fatty change)
During chemical cell injury, elaborate on the plasma membrane damage
- caused by products of lipid peroxidation in the smooth ER
- cellular swelling
- massive influx of Ca -> mit calcification, denaturation of cellular proteins, cell death
define heterolysis
- cellular degradation by enzymes derived from sources extrinsic to cell (e.g. bacteria, leukocytes)
Name the 6 types of necrosis
1. Coagulative
2. Liquifactive
3. Caseous
4. Gangrenous
5. Fibrinoid
6. Fat
Coagulative necrosis
- results from ischemia, particularly of kidney and heart
- early stage: preservation of tissue architecture
- increased cytoplasmic eosinophilia
- nuclear changes
why do you get increased cytoplasmic eosinophilia during coagulative necrosis?
- protein denaturation and loss of cytoplasmic RNA
Nuclear changes that are the hallmarks of irreversible cellular injury
1) Pyknosis
2) Karyorrhexis
3) Karyolysis
4) Dissapearance of stainable nuclei
- chromatin clumping and shrinking with increased basophilia
- fragmentation of chromatin
- fading of chromatin material
liquifactive necrosis
enzymatic liquefaction of necrotic tissue, most often in the CNS, where it is caused by ischemia. Can also occur in areas of bacterial infection
Caseous necrosis
- shares features of both coagulation and liquefaction necrosis.
- seen in TB granulomas
Pathologic changes in caseous necrosis
- architecture not preserved, but tissue not liquefied
- soft and cheese-like
- on histology, increased affinity for acidophilic dyes
describe the cellular mediators of caseous necrosis
- occurs as part of a granulomatous inflammation
- interactin of T lymphocytes (CD4, CD8, CD4-, CD8-), macrophages, INF-g
what type of necrosis does 'amorphous eosinophilic appearance' describe?
caseous necrosis
fibrinoid necrosis
- characterized by deposition of fibrin-like proteinaceous material in walls of arteries; often observed as part of immune-mediated vasculitis
gangrenous necrosis
- ischemia to lower extremity or bowel
what is wet gangrene?
gangrenous necrosis when complicated by infective heterolysis and consequent liquefactive necrosis
what is dry gangrene?
gangrenous necrosis when characterized primarily by coagulative necrosis without liquefaction
what type of necrosis is described as being 'smudgy pink in vascular walls; actual necrosis may or may not be present'
fibrinoid necrosis
what are the two forms of fat necrosis?
1. traumatic fat necrosis
2. enzymatic fat necrosis
traumatic fat necrosis
- occurs after severe injury to tissue with high fat content (e.g. breast tissue)
enzymatic fat necrosis
- a complication of acute hemorrhagic pancreatitis
1. proteolytic and lipolytic pancreatic enzymes diffuse into inflammed tissue and digest the parenchyma
2. fatty acids liberated by diggestion form calcium sals (saponification)
3. vessels are eroded -> hemorrhage
biochemical differences between necrosis and apoptosis
Necrosis: no gene involvement or new protein synthesis; DNA fragemtnation is irregular -> electrophoretic smudge pattern
Apoptosis: gene expression, protein synthesis, and energy consumption; DNA fragmentation is regular -> laddered pattern
morphologic features of apoptosis
- involves involution and shrinkage -> results in small round eosinophilic masses with chromatin remnants (e.g. Councilman bodies in viral hepatitis)
extrinsic pathway of apoptosis
- mediated by cell surface receptors (FAS). FAS ligand signals for activation of caspase cascade
what family does FAS belong to?
the tumor necrosis factor receptor family of proteins
which are the initial caspases involved in the caspase cascade (apoptosis)
- caspase 8 and 9
which are the terminal caspases involved in the caspase cascade (apoptosis)
- caspase 3 and 6
intrinsic/mitochondrial pathway of apoptosis
- initialed by loss of stimulation by growth factor -> loss of bcl-2 from the inner mit membrane
- increase mit permeability, realease of cyt c, and stimulationof proapoptotic proteins (bax and bak)
- cyt c interacts with apaf-1 causing self-cleavage and activation of caspase-9
- downstream caspases are activated to cleave targets
cytotoxic T-cell activation of apoptosis
- direct activation of caspases by grnzyme B, a cytotoxic T-cell protease that directly activates the caspase cascade
- entry of granzyme B into target cells is mediated by perforin
what makes perforin?
cytotoxic T cells
what makes up the 'laddering' appearance of apoptotic DNA?
- chromatin fragments that are multiples of 180-200 bps
what do transglutaminases do during apoptosis?
- crosslink apoptotic cytoplasmic proteins
list some genes that regulate apoptosis
- bcl-2: inhibits apoptosis
- bax: facilitates apoptosis
- p53: facilitates apoptosis by decreasing transcription of bcl-2 and increasing transcription of bax