Lecture 3.1 MJ slides Flashcards
List and define each type of toxin
1) Direct-acting: combine with critical molecular component or cellular organelle, disrupting its function i.e. mercury
2) Latent toxins: these are converted from benign to reactive metabolites which act on target cells
3) Reactive Oxygen Species (ROS): free radicals that are highly reactive and react with cellular components, destroying them
Mercury is an example of what kind of toxin?
Direct-acting
1) What kind of toxins are converted from benign to reactive metabolites which act on target cells?
2) What are free radicals that are highly reactive and react with cellular components, destroying them, called?
1) Latent toxins
2) Reactive oxygen species (ROS)
Summarize the 4 types of adaptation to cellular stress
1) Hypertrophy: increased cell size
2) Hyperplasia: increased cell number
3) Atrophy: decreased cell size
4) Metaplasia: change in adult cell type
Out of the 4 forms of adaptation:
1) Which reference cell size?
2) Which references cell number?
3) Which refers to cell type?
1) Hypertrophy and atrophy
2) Hyperplasia
3) Metaplasia
List the 5 steps of coagulative necrosis
1) Ischemia/Infarct
2) Drop in ATP production
3) Glycogen supply allows for anerobic metabolism
4) Late stage = membrane bound organelles burst
5) Cell ruptures
Coagulative necrosis:
1) Where does ischemia/ infarct usually occur?
2) What does a drop in ATP production lead to? What does this then cause?
1) Occurs in places with stores of glucose
2) Na/K pumps fail
Cell swells > pale and firm gross appearance
Coagulative necrosis:
1) What does glycogen supply allow for? What does this produce?
2) What does this do to pH? What does this cause?
1) Allows for anerobic metabolism; lactate is produced
2) pH falls; proteins are denatured!
Coagulative necrosis:
1) What happens during the late stage? What doesn’t happen?
2) What happens when the cell ruptures?
1) Membrane bound organelles burst; lysosomes spill their contents
-Lysis of cellular architecture does not occur
2) Ca enters the cell; macrophages and neutrophils flood in; inflammation ensues
Liquefactive necrosis:
1) What causes it?
2) Does this affect pH? Explain
1) CNS infarct/ Pyogenic Infxn
2) CNS is highly active tissue and glucose/glycogen poor
-Thus, no anerobic metabolism; pH does not fall
Liquefactive necrosis:
1) Do ATP pumps fail? Does the cell swell?
2) Do the organelles rupture?
1) ATP pumps still fail and cell swells
2) Organelles rupture; lysosomes spill their contents
Liquefactive necrosis:
1) Are the enzymes still active after lysosomes spill their contents? Explain
2) What happens in a pyogenic infection?
3) What does this look like on microscopy?
1) Yes, so you get cellular soup!
2) Neutrophils / bacteria emit lytic enzymes
3) Soupy vacuoles give “moth eaten” appearance
Caseous necrosis:
1) What organism can do this?
2) What is a granuloma?
3) What happens within the granuloma?
4) What do they look like?
1) TB (& maaaaybe fungus)
2) “Walling off” of infected area by macrophages
3) They attempt to destroy everything inside their perimeter
4) Pink patches surrounded by blue nuclei of macrophages
Fat Necrosis:
1) What are the two causes?
2) How are pancreatic enzymes involved?
3) What happens after the pancreatic enzymes do their thing?
4) What does this look like on microscopy?
1) Enzymatic or traumatic
2) Adipose tissue contains triglycerides which are dismantled by pancreatic enzymes
3) Calcium binds; Salt + lipids = soap “saponification”
4) White spots are noted on gross evaluation and upon microscopy
Fibrinoid necrosis:
1) What causes it?
2) Where does it occur?
3) What is happening when this occurs?
1) Hypersensitivity rxn
2) Occurs in blood vessels
3) Sequestered RBC’s surrounded by fibrous material
Intrinsic pathway:
1) When its time to self destruct, The BAD protein is produced which binds to what?
2) What does this allow?
3) What does this ultimately let out?
1) BCL-2
2) Bax bak door to come together and let out
3) Cytochrome c CASPACES 8,9 3
What key 3 things start the intrinsic pathway of apoptosis?
1) Planned death as a part of embryonic development
2) Failure to receive external signals from outside the cell that prevent destruction
3) P53 tumor suppressor activity
P53 tumor suppressor gene creates what?
P53 protein
What can P53 protein do? (at 3 diff concentrations)
1) Low concentrations of P53 initiate DNA repair mechanisms
2) Medium concentrations of P53 arrest cellular reproduction
3) High concentrations of P53 induces the production of BAD > BCL2 > bax/bak > lets out Cytochrome C > initiates CASPACES 8,9 > 3
Which pathway of apoptosis is more common?
Intrinsic
Give a summary of the intrinsic pathway of apoptosis
1) Programed death as a part of embryonic development
2) Loss of growth factors at cell membrane
Inhibition of BCL2 through BAD protein pairing> Bax/Bak dimer > Cyt C ? CASPASE 8,9 > CASPASE 3 >
3) Genetic mutation leading to DNA damage or bad protein product
-A little bit of P53 = DNA repair mechanisms
-A moderate amount of P53 = DNA repair + arrest cell cycle
-A lot of P53 > BAD binds to BCL2 = Bax/Bak dimerize = Cyt C leaves mitochondria > CASPASES 8,9 CASPASE 3 >
Give a summary of the extrinsic pathway of apoptosis
Self-reactive T cell presents antigen to death receptor (TNF-alpha, Fas Fas) > CASPASE cascade > CASPASE 3 > apoptosis
What are the two major steps of inflammation?
1) Increases blood flow (vasodilation)
2) Makes vessels more permeable (permeability)
1) What does the increase in permeability and vasodilation during inflammation lead to?
2) Define exudate
1) This leads to the escape of fluid proteins and blood cells from the vascular system into the interstitial tissues or body cavities
2) Has high protein concentration and contains cellular debris
1) Describe the properties of transudate
2) What is this a result of?
1) Transudate by contrast has low protein content, little cellular material, low specific gravity
2) Osmotic pressure or hydrostatic imbalance across vessels with normal permeability
1) Vasodilation is induced mostly by what? What does this act on?
2) What is vasodilation one of the earliest manifestations of? What does it lead to?
3) Vasodilation is followed by increases in what 2 things?
1) Histamine released by mast cells; vascular smooth muscle
2) One of the earliest manifestations of acute inflammation; increases flood flow
3) Increased permeability and exudative fluid
1) After vasodilation is followed by increased permeability and exudative fluid, what does this eventually lead to?
2) What happens at this point?
3) What does this cause? (actually and visually)
1) Exudate build up in the extravascular tissues
2) Blood flow slows now
3) Vessels become engorged with slow moving red cells
-What we see up on gross inspection is erythema
1) _______________ last longer and are slower to arrive, eventually support collagen formation, which adds to the changes of chronic inflammation
2) _________________ come faster and live longer, do more destruction at the site of acute inflammation – sometimes with negative effect
1) Macrophages
2) Neutrophils
True or false: Leukocytes as a whole can do more harm than good in some disease. Explain or give examples.
True; TB, hepatitis, both with prolonged host response does more damage than the microbe
How can leukocytes sometimes do more harm than good?
1) Granule enzymes and anti-microbial proteins may be released into the extracellular environment.
2) The mechanisms that function to eliminate microbes and dead cells (the physiologic role of inflammation) also are capable of damaging normal tissues (the pathologic consequences of inflammation)
Differentiate between acute and chronic inflammation
1) Acute: Occurs in minutes to hours and lasts from hours to days
-Exudation of fluid and plasma proteins – causing edema
-Emigration of leukocytes, mostly neutrophils (PMNs) + macrophages (to a lesser degree)
2) Chronic: Longer duration
-Associated with more tissue destruction
-Presence of macrophages
-Proliferation of blood vessels
-Fibrosis
Acute vs chronic inflammation:
1) Which involves fibrosis?
2) Which is assoc. with more tissue destruction?
3) Which is marked by the emigration of mostly neutrophils (PMNs) and macrophages?
1) Chronic
2) Chronic
3) Acute
The use of prostaglandin inhibitors has two major side effects; what are they?
very important to know
1) Peptic ulcer
2) Acute and chronic kidney disease
1) Chronic Inflammatory Disease is suppressed with Agents that block what?
2) What is this?
1) TNF
2) TNF is a major cytokine of leukocyte
