Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
142 Cards in this Set
- Front
- Back
|
Hypertrophy:
|
Increased size of organ or tissue dt increase in SIZE of cells
|
|
|
2 changes that cause the increase in cell size:
|
-Increased protein synth
-Increased size/number of intracellular organelles |
|
|
Why does hypertrophy occur?
|
So cells can adapt to increased workload
|
|
|
2 examples of hypertrophy in response to increased workload:
|
-Skeletal muscle mass in response to exercise
-Left Ventricular hypertrophy in hypertensive heart disease |
|
|
Hyperplasia:
|
Increased size of organ or tissue dt increase in NUMBER of cells
|
|
|
Example of hyperplasia:
|
Glandular proliferation in breast during pregnancy
|
|
|
Example situation of both hyperplasia and hypertrophy occurring together:
|
Gravid Uterus: smooth muscles undergo both processes.
|
|
|
BPH
|
Benign prostatic hyperPLASIA
|
|
|
Aplasia:
|
Failure of cell production
|
|
|
Result of Aplasia during fetal development:
|
Agenesis - organ fails to form because of failure of cell production.
|
|
|
How can aplasia occur later in life?
|
If precursor cells in proliferative tissues like the bone marrow are permanently lost
|
|
|
Decrease in cell production that is less extreme than in aplasia:
|
Hypoplasia
|
|
|
2 syndromes where hypoplasia is seen:
|
-Klinefelter's
-Turners |
|
|
What is hypoplastic in Klinefelter's/Turners?
|
Gonadal structures
|
|
|
Atrophy:
|
Decreased size of organ/tissue dt decrease in mass of PRE-EXISTING cells
|
|
|
Most common causal factors of atrophy:
|
-Disuse
-Denervation -Aging -Decreased hormone stimulation -Deprivation of O2/nutrients |
|
|
Hallmark finding in Atrophy:
|
AUTOPHAGIC GRANULES
|
|
|
Autophagic granules are what?
|
Intracytoplasmic vacuoles containing debris from degraded organelles.
|
|
|
Pathway involved in atrophy:
|
Ubiquitin-Proteosome pathway of protein degradation
|
|
|
Metaplasia:
|
Replacement of one differentiated tissue by another
|
|
|
3 common examples of metaplasia:
|
-Squamous
-Osseous -Myeloid |
|
|
Explain and given an example of Squamous metaplasia:
|
Columnar -> Squamous at the squamocolumnar junction of the cervix
|
|
|
3 other sites where Squamous metaplasia can occur:
|
-Respiratory epithelium of bronchus
-Endometrium -Pancreatic ducts |
|
|
2 conditions associated with causing squamous metaplasia:
|
-smoking
-vit A deficiency |
|
|
Metaplasia reversible or non?
|
Reversible
|
|
|
Osseous metaplasia is:
|
Formation of new bone at sites of tissue injury
|
|
|
Myeloid metaplasia is:
|
Extramedullary hematopoiesis
|
|
|
2 sites of Extramedullary hematopoiesis
|
-Liver
-Spleen |
|
|
Cause of hypoxic cell injury:
|
Anoxia/hypoxia
|
|
|
5 mechanisms leading to anoxia/hypoxia:
(which is most common) |
-CO poisoning
-Anemia -Pulmonary disease leading to poor oxygenation of blood -Ischemia - most common -Decreased tissue perfusion w/ adequetely oxygenated blood |
|
|
What is the difference btwn ischemia and decreased tissue perfusion?
|
Ischemia is obstruction of bloodflow; decreased perfusion is lack of oomph
|
|
|
What are 3 situations in which Decreased tissue perfusion occurs?
|
-Cardiac failure
-Hypotension -Shock |
|
|
Cell organelle first affected by hypoxia; 2 results?
|
Mitochondria
-Decreased oxidative phosphorylation -Depletion of ATP |
|
|
3 major consequences of decreased ATP:
|
-Na/K ATPase failure
-Ribosome disaggregation so Protein synthesis failure -PFK stimulation |
|
|
How does failure of the Na/K pump alter the cell?
|
-Increases Na/Water inside cell
-Decreases K inside cell Cell swells |
|
|
What is cellular swelling called?
|
Hydropic change
|
|
|
Morphologic feature of hydropic change:
|
Large cytoplasmic vacuoles
|
|
|
What is one of the first ultrastructural changes evident early in reversible injury?
|
Swelling of Endoplasmic Reticulum
|
|
|
What ultrastructural change develops after the ER swells?
|
Mitochondrial swelling
|
|
|
What is the result of phosphofructokinase stimulation in response to decreased ATP?
|
Cell glycolysis increases
|
|
|
2 things that accumulate in early stage cell injury due to increased glycolysis:
|
-Lactate
-Acid |
|
|
What does Acidification of the cell result in?
|
Reversible clumping of nuclear chromatin
|
|
|
What is the main thing that happens in late stage hypoxic cell injury?
|
Membrane damage (to all organelle membranes) and loss of membrane phospholipids
|
|
|
2 morphologic signs of REVERSIBLE cell damage:
|
-Myelin figures
-Cell blebs |
|
|
Final result of severe/prolonged hypoxic cell injury:
|
Cell death
|
|
|
What marks the point of no return in cell injury?
|
Irreversible damage to cell membranes
|
|
|
What is the main thing caused by the massive cell membrane damage that leads to cell death?
|
Massive calcium influx and calcification of mitochondria
|
|
|
What gets released when cells in circulation lose their membrane integrity?
|
Intracellar enzymes and proteins
|
|
|
3 enzymes that get released in myocardial cell damage (MI):
|
-AST: aspartate aminotransferase
-LDH: lactate dehydrogenase -CK: Creatine kinase |
|
|
2 myocardial proteins that are replacing the former enzymes as markers of myocardial necrosis:
|
-Troponins - TnI/TnT
-Myoglobin |
|
|
3 enzymes that are markers of liver damage:
|
-AST
-ALT -ALP -GGT |
|
|
How do different cells in different tissues differ in terms of degree of damage that occurs in hypoxia?
|
By differences in vulnerability
|
|
|
When does hypoxic injury become irreversible for:
-Neurons -Myocardial cells -Hepatocytes -Skeletal muscle cells |
Neurons: 3-5 min
Myocardial: 1-2 hours Hepatocytes: 1-2 hours Sk mm cells: many hours |
|
|
What is a free radical?
|
Molecule with a single unpaired electron in the outer orbital
|
|
|
Examples of free radicals:
|
Hydroxyl radical oh*
Superoxide O2*- |
|
|
6 mechanisms that generate free radicals:
|
NOIDUR
-Normal metabolism -Oxygen toxicity -Ionizing radiation -Drugs/chemicals -UV light -Reperfusion after ischemia |
|
|
What are 2 examples of oxygen toxicity?
|
-Alveolar dmg in adults leading to ARDS - resp distress syndrome
-Retrolental fibroplasia |
|
|
What is retrolental fibroplasia?
|
Retinopathy of prematurity which leads to blindness in premature infants
|
|
|
Why is oxygen toxicity associated with retinopathy of prematurity? How do we know there is a link?
|
Because it causes abnormal vascularization of the retina - investigators found high levels of O2 in incubators of neonates associated with increased ROP.
|
|
|
What is the mechanism by which many drugs/chemicals generate free radicals?
|
By induction of P450 mixed function oxidases in SER and by promoting SER proliferation.
|
|
|
What is a classic drug intoxication associated with SER proliferation and hypertrophy in the liver?
|
Barbiturates
|
|
|
What are 3 mechanisms cells have for degrading free radicals?
|
-Intracellular enzymes
-Exogenous/endogenous Antioxidants -Spontaneous decay |
|
|
3 intracellular enzymes that degrade free radicals:
|
-Superoxide dismutase
-Glutathione peroxidase -Catalase |
|
|
3 vitamin antioxidants:
|
ACE
|
|
|
5 nonvitamin antioxidants:
|
Cysteine
Ceruloplasmin Glutathione Selenium Transferrin |
|
|
What is the model that illustrates chemical cell injury?
|
Liver cell membrane damage induced by CCL4 - carbon tetrachloride
|
|
|
How does CCL4 cause cell membrane damage?
|
By being processed by the P450 system to produce CCL3* which is highly reactive
|
|
|
How does the highly reactive free radical CCL3* cause damage?
|
By lipid peroxidation of intracellular membranes
|
|
|
2 main results of the widespread intracell membrane damage by CCL3*:
|
-Ribosome disaggregation
-Plasma membrane damage |
|
|
Ribosome disaggregation in a liver cell leads to:
|
-Lack of proteins - apoproteins
-Fatty Change!! Accumulation of intracellular lipids |
|
|
What are the 2 hallmark changes resulting from lipid peroxidation in the smooth ER?
|
-Cellular swelling
-Massive Ca influx |
|
|
2 contrasting patterns of tissue death:
|
-Necrosis
-Apoptosis |
|
|
Necrosis:
|
Sum of degradative/inflammatory reactions after tissue death caused by INJURY
|
|
|
In what organisms does necrosis occur?
|
LIVING
|
|
|
What is Autolysis?
|
Degradative reactions within cells by intracellular enzymes that are INDIGENOUS
|
|
|
When does Autolysis occur naturally?
|
Postmorten
|
|
|
Is postmorten autolysis necrosis?
|
NO - necrosis occurs in LIVING organisms.
|
|
|
What is Heterolysis?
|
Degradative reactions within cells by enzymes that are EXOGENOUS - ie bacterial, from white cells, etc.
|
|
|
6 kinds of necrosis:
|
-Coagulative
-Liquefactive -Caseous -Gangrenous -Fibrinoid -Fat |
|
|
What is the classic cause of Coagulative necrosis?
|
Ischemia - particularly the heart/kidney
|
|
|
Why is coagulative necrosis often seen in the heart/kidney?
|
Bc these organs have end-artery supplies and limited collateral supply.
|
|
|
2 main morphologic features of coagulative necrosis:
|
-Preserved tissue architecture
-Increased eosinophilia |
|
|
Hallmark of irreversible cell injury and necrosis:
|
NUCLEAR CHANGES
|
|
|
What 4 nuclear changes are seen in irreversible coagulative necrosis?
|
-Pyknosis
-Karyorrhexis -Karyolysis -Stainable nuclei disappear |
|
|
Pyknosis:
|
Chromatin clumping/shrinking
Increased basophilia |
|
|
Karyorrhexis:
|
Chromatin fragmentation
|
|
|
Karyolysis:
|
Fading of chromatin material
|
|
|
What pattern of necrosis occurs in ischemia of the CNS?
|
Liquefactive necrosis
|
|
|
What is the cause of COAGULATIVE necrosis?
|
Protein denaturation
|
|
|
What is the cause of LIQUEFACTIVE necrosis?
|
Autolysis - enzymatic degradation of necrotic tissue
|
|
|
Where else is liquefactive necrosis sometimes seen?
|
Bacterial Suppurative infections
|
|
|
What is the characteristic feature that forms in Suppurative liquefactive necrosis?
|
PUS
|
|
|
What is pus?
|
Liquefied tissue debris and PMNs
|
|
|
What process is Caseous Necrosis a component of?
|
Granulomatous inflammation!
|
|
|
What are important players in granulomatous inflammation?
|
T lymphocytes
Macrophages Cytokines like IFN-y |
|
|
What is the leading cause of caseous necrosis?
|
TB
|
|
|
What is caseous necrosis like?
|
A combination of both coagulative and liquefactive necrosis
|
|
|
What does caseous necrosis look like grossly?
|
cheese
|
|
|
What is the morphologic appearance of caseous necrosis under the microscope?
|
Amorphous and Eosinophilic
|
|
|
At what sites in the body is gangrenous necrosis most commonly seen?
|
-Bowel
-Lower limbs |
|
|
What is Gangrenous necrosis secondary to?
|
Vascular occlusion
|
|
|
What is gangrenous necrosis that is complicated by infective heterolysis and ensuing liquefactive necrosis called?
|
Wet gangrene
|
|
|
What is dry gangrene?
|
Mostly just coagulative necrosis, little/no liquefactive.
|
|
|
What is fibrinoid necrosis?
|
Deposition of fibrin-like proteinaceous particles in arterial walls.
|
|
|
What is fibrinoid necrosis associated with often?
|
Immune-mediated Vascular damage
|
|
|
What are 2 forms of Fat necrosis?
|
-Enzymatic
-Traumatic |
|
|
What is a common example of traumatic fat necrosis?
|
That in the breast
|
|
|
In what condition is Fat necrosis seen as a complication?
|
Acute pancreatitis
|
|
|
Why does fat necrose in Acute pancreatitis?
|
Because of the release of lipase along with the other digestive enzymes.
|
|
|
What hallmark feature forms due to fat necrosis in Acute pancreatitis?
|
Saponification - SOAP
|
|
|
How does Saponification occur?
|
FFA's form Calcium salts
|
|
|
What is the non-necrosis morphologic pattern of cell death?
|
Apoptosis
|
|
|
What are 2 important examples of Apoptosis that help us remain healthy?
|
-Automatic removal of cells with irreparably damaged DNA
-Physiologic cell removal during embryogenesis or menstruation |
|
|
What is the etiology of necrosis?
|
Gross irreversible cell injury
|
|
|
What is the etiology of apoptosis?
|
-Subtle cell damage (DNA)
or -It was planned/physiologic |
|
|
What is the nature of cell involvement in necrosis? Apoptosis?
|
Necrosis: many contiguous cells
Apoptosis: single or small clusters of cells |
|
|
What happens to the cytoplasm in necrosis vs apoptosis?
|
Eosinophilia increases in both
|
|
|
How does the general cell size change in necrosis vs apoptosis?
|
Necrosis: cells swell
Apoptosis: cell shrinks |
|
|
What morphologic changes are seen in the nuclei of cells in
-Apoptosis -Necrosis |
In BOTH there is nuclear chromatin condensation and fragmentation.
|
|
|
Which form of cell death would be considered passive and which would be active? Why?
|
Necrosis = passive
Apoptosis = active - because it involves gene expression, protein synthesis, and energy |
|
|
What is the pattern of nuclear fragmentation seen in necrosis vs apoptosis? How do we know?
|
Necrosis: haphazard fragmentation
Apoptosis: regular -Because electrophoresis shows a smear in necrosis and a ladder pattern in apoptosis |
|
|
In which pattern of cell death is there an inflammatory reaction?
|
Necrosis - NOT apoptosis!
|
|
|
What special cells appear when apoptosis occurs in hepatocytes affected by viral hepatitis?
|
Councilman bodies
|
|
|
What are councilman bodies?
|
Small round eosinophilic masses containing chromatin remnants.
|
|
|
What are the 2 biochemical pathways of apoptosis initiation?
|
-Intrinsic
-Extrinsic |
|
|
What is the extrinsic pathway of apoptosis mediated by?
|
Fas/Fas ligand
|
|
|
What is initiated by Fas/fasL interaction?
|
The caspase pathway
|
|
|
What are initial activating caspases?
|
Caspase 8 and 9
|
|
|
What are terminal caspases - the executioners?
|
Caspase 3 and 6
|
|
|
What is the intrinsic pathway initiated by?
|
Loss of growth factor stimulation or other adverse stimuli
|
|
|
What does loss of growth factor stimulation lead to in the intrinsic pathway of apoptosis?
|
Loss of Bcl-2 from the inner mitochondrial membrane.
|
|
|
What does loss of bcl-2 lead to?
|
Increased mitochondrial permeability so release of cytochrome c
|
|
|
What does cytochrome c release lead to?
|
Activation of bax and bak and cyto c interacts with APAF1
|
|
|
What does Cyto-C interaction with APAF1 lead to?
|
Cell cleavage and activation of Caspase 9 and the caspase pathway!
|
|
|
How do CTL's activate apoptosis?
|
By directly activating caspases with granzyme B
|
|
|
How does the Granzyme B from CTLs get into the target cell?
|
By perforin
|
|
|
What phenomenon in the DNA of apoptotic cells is highly characteristic of apoptosis?
|
Laddering on Electrophoresis
|
|
|
What 3 genes/gene products are responsible for regulation of apoptosis?
|
-Bcl-2
-Bax -p53 |
|
|
What does the gene product of Bcl-2 do?
|
Inhibits apoptosis
|
|
|
What does the gene product of Bax do?
|
Facilitates apoptosis
|
|
|
What does the gene product of p53 do?
|
Facilitates apoptosis by decreaing bcl2 transcription and increasing that of Bax!
|
|
|
finish reversible cell changes and accumulations
|
ok
|
