Unit 2 Lectures Flashcards
What are the four cellular adaptations to stress?
- hypertrophy (increased size of cells)
- hyperplasia (increased number of cells)
- atrophy (decreased size and functional capacity)
- metaplasia (one cell type replaced by another)
What is the mechanism of atrophy?
decreased protein synthesis, increased protein degradation (ubiquitin-proteasome pathway)
What are the two types of reversible cell injury?
- swelling: failure of energy-dependent ion pumps
- fatty changes: accumulation of lipid vacuoles due to increased synthesis of fatty acids
Accumulation of lipid in hepatocytes is a sign of (reversible/irreversible) injury and is (specific/non-specific)
reversible, non-specific
intracellular changes associated with reversible cell injury
- plasma membrane alterations
- mitochondrial changes
- dilation of ER with detachment of ribosomes
- chromatin clumping
What are two types of irreversible cell injury?
- apoptosis
- necrosis
During irreversible cell injury, there are increased ____________ and decreased ___________ in the cytoplasm (cell types)
eosinophilia, basophils
pyknosis
- nuclear shrinkage (DNA condenses)
- increased basophilia
karyorrhexis
pyknotic nucleus fragments
karyolysis
dissolution of nucleus (basophils fade, breakdown of denatured chromatin)
In an H&E stain, nucleic acids stain _________ using a ______ dye and ____________ stain _________
- blue, basic (nucleic acids are acidic)
- eosinophils, pink (eosinophils are basic)
coagulative necrosis
- tissue architecture preserved for several days (due to structural damage)
- tissue appears pale
___________ necrosis is typically seen in hearts following MI (characteristic of infarcts)
coagulative
Bacterial infections and hypoxia in the CNS often lead to ____________
liquefactive necrosis
In liquefactive necrosis, microbes (bacterial, fungal) stimulate the accumulation of __________ cells and ___________ digest the tissue
inflammatory, leukocyte enzymes
What type of necrosis is characteristic of TB?
caseous
_____________ is characteristic of caseous necrosis
granulomatous inflammation
What is a histiocyte?
a macrophage (giant cell with lots of nuclei)
Fat necrosis is typically seen following what events?
acute pancreatitis, trauma
____________ is an immune reaction in which complexes of antigens and antibodies are deposited in the walls of arteries
fibrinoid necrosis
What type of necrosis is seen in vasculitis?
fibrinoid
If you disrupt the Ca2+ gradient, you get a(n) (influx/efflux) of Ca2+, leading to ____________
influx, decreased ATP (nuclear damage)
What are the two major pathways for cell injury by free radicals?
- redox reactions during mitochondrial respiration (normal)
- phagocytic leukocytes
What can assist with removal of ROS? (3)
- SOD
- glutathione peroxidase
- catalase
What are caspases?
cysteine proteases that cleave proteins after aspartic residue (in apoptosis)
What are the two main pathways of apoptosis?
- mitochondrial (intrinsic)
- death receptor (extrinsic)
The initiator caspase for the mitochondrial pathway is caspase ___ and the caspase for the death receptor pathway is ___
9, 8
What is autophagy?
cell eats its own contents
What are the 4 main pathways of intracellular accumulation?
- inadequate removal
- failure to degrade
- accumulation of abnormal endogenous substance
- accumulation of abnormal exogenous substance
Describe the difference in cellular infiltrate between acute and chronic inflammation
acute: neutrophils
chronic: monocytes, macrophages, lymphocytes
stimuli for acute inflammation
infection, trauma, foreign material, immune reaction
What is an inflammasome?
a complex of proteins that mediates cellular responses (especially to dead/damaged cells but also microbes)
A drop in _________ can stimulate the inflammasome.
intracellular K+
Inflammasomes activate _______, which cleaves ________ to its active conformation, which leads to inflammation
caspase 1, IL-1B
Two vascular changes during acute inflammation are _________ and _________
- increased vessel permeability
- increased blood flow
Endothelial cells _________ as a response to mediators
contract
What are some early and late mediators that affect acute inflammation?
early: histamine, bradykinin
late: IL-1, TNF
Exudate vs. transudate: common cause: protein content: (increased/decreased) cell content: (increased/decreased) specific gravity: (high/low)
Exudate vs. transudate: common cause: increased vascular perm; altered intravascular pressure protein content: increased; decreased cell content: increased; decreased specific gravity: high; low
In leukocyte recruitment, the endothelium is induced to move adhesion molecules to the surface by ________ and _________ (chemical mediators)
histamine (p-selectin)
IL-1 (E-selectin)
What are the two general ways for leukocytes to bind foreign material?
- receptors for specific products of microbes or necrotic cells
- receptors for opsonins
What are opsonins?
host proteins in the blood or produced locally that coat microbes (i.e.: IgG, C3b)
What types of cells are involved in chronic inflammation?
- mononuclear cell infiltrate:
- plasma cells
- lymphocytes
- monocytes
- macrophages
- eosinophils
- mast cells
Settings characterized by chronic inflammation (3)
- persistant infection
- immune-mediated disease (autoimmune, allergy)
- prolonged exposure to toxins
What is the main phagocyte in the adaptive immune response?
macrophages
What activates M1 macrophages?
- endotoxin
- INFgamma
- foreign material
What activates M2 macrophages?
- IL-4
- IL-13
What do M1 macrophages produce?
- ROS
- NO
- lysosomal enzymes
- proinflammatory cytokines
What do M2 macrophages produce?
Growth factors for…
- new vessel growth
- fibroblast activation
What are the main functions of M1 macrophages?
- killing microbes
- chronic inflammation
What are the main functions of M2 macrophages?
- tissue repair
- fibrosis
Th1 CD4+ T lymphocytes secrete _______, which activates the _________ pathway for macrophages
INFgamma, classical
Th2 CD4+ T lymphocytes secrete ________, which activates the _________ pathway for macrophages
IL-4, IL-5, IL-13, alternative (and activates eosinophils)
Th17 CD4+ T lymphocytes secrete ________, which recruits _________ and _________
IL-17, neutrophils, monocytes
Eosinophils are involved in ________ inflammation
chronic
What is granulomatous inflammation and when does it occur?
- enlarged macrophages form a nodule, which is often surrounded by lymphocytes
- chronic inflammation
What (3) mediators are responsible for the systemic effects of inflammation?
TNF, IL-1, IL-6
Vascular cells in the _______ are stimulated by _______ to produce __________ that lead to __________
hypothalamus, pyrogens, prostaglandins, fever (pyrexia)
What two proteins adhere to cell walls and act as opsonins?
- C-reactive protein (CRP)
- serum amyloid A (SAA)
More leukocytes get released from the bone marrow during inflammation under the influence of ______ and _______
IL-1, TNF
Continued inflammation leads to increased production of __________ that increases bone marrow production of leukocytes
colony-stimulating factor
What is suggested by an increase in …?
- neutrophils
- lymphocytes
- eosinophils
- decreased leukocytes
- neutrophils: bacterial
- lymphocytes: viral
- eosinophils: asthma, parasitic infection
- decreased leukocytes: specific infection (i.e.: Typhoid)
Vasoactive amines are (cell-derived/plasma protein derived) mediators and include __________ and ____________
cell-derived; histamine and serotonin
What type of cells release histamine?
mast cells
Serotonin is found in _________ and is important in (vasodilation/vasoconstriction)
platelets, vasoconstriction
What are some sources of arachidonic acid?
leukocytes, mast cells, endothelium, platelets
What are the two pathways along which arachidonic acid is produced?
cyclooxygenase: prostaglandins, thromboxanes
lipoxygenase: leukotrienes, lipoxins
NSAIDs block _______________
cyclooxygenase
Glucocorticoids block ___________
phospholipase A2
Leukotrienes mediate ___________
inflammation
Lipoxins antagonize ___________ and are ___________
leukotrienes, anti-inflammatory
What are some functions of platelet-activating factors?
- platelet aggregation
- vasodilation
- vascular permeability
- bronchoconstriction
TNF and IL-1 are examples of ___________
cytokines
TNF and IL-1 cause _____________
endothelial activation (leukocyte binding and recruitment)
INFgamma stimulates…
classical M1 macrophage activation
IL-12 stimulates…
growth and function of T cells
ROS are released from … (2)
- activated neutrophils
- macrophages
What are some of the roles of NO?
- free radical that kills microbes
- mediates vasodilation
- antagonizes platelet activation
- reduces leukocyte recruitment
alpha-1-antitrypsin
-protease inhibitor (neutralizes proteases that are active outside the cell, limits damage to host tissue)
Neuropeptides can initiate __________
inflammation
Substance P is an example of a ____________
neuropeptide (initiates inflammation)
T/F: Complement is systemically in circulation
true
What are the results of activated complement…?
- C3a, C5a
- C5a
- C3a, C4a, C5a
- C3b
- the MAC
- C3a, C5a: increase vascular permeability (histamine release)
- C5a: AA metabolism
- C3a, C4a, C5a: activate leukocytes
- C3b: enhanced phagocytosis
- the MAC: creates pores that violate bacterial membrane
Factor ___ is an important clotting factor that activates the _______ system
XII, clotting
What are some anti-inflammatory mediators?
- lipoxins (antagonize leukotrienes)
- C1 inhibitor (complement)
- IL-10 (downregulates macrophages)
- TGFbeta (promotes fibrosis)
What are labile tissues?
tissues that are continuously dividing
What are the two characteristics of stem cells?
- self-renewal
- asymmetric replication
Are adult stem cells more or less undifferentiated than embryonic stem cells?
less undifferentiated
What are some roles of the ECM in tissue repair?
- proliferation
- differentiation and movement of cells
- substrate for cell adhesion and migration
- reservoir for growth factors
What are the 3 components of the ECM?
- fibrous structural proteins (collagen, elastins)
- water-hydrated gels (proteoglycans, hyaluronan)
- adhesive glycoproteins
T/F: If the ECM is damaged, repair can only be accomplished by tissue regeneration
true
What organ has the most robust regenerative capacity?
liver
_______% of the liver can be removed in living-donor transplant
40-60%
In angiogenesis, increased permeability is induced by ________
VEGF
What are some steps in angiogenesis?
- periocytes detach
- degradation of basement membrane
- recruitment of periendothelial cells to form mature vessels
What are the main growth factors that orchestrate deposition of ECM proteins during tissue repair?
PDGF, FGF2, TGFbeta (come from M2 macrophages)
____________ accomplish the degradation of collagens and other ECM components (remodeling)
matrix metalloproteases
What are some systemic factors that influence tissue repair?
- nutritional: impair collagen synthesis
- metabolic: delay repair
- vascular: ischemia, venous drainage
A ___________ is a hypertrophic scar that does not regress
keloid
What is first intention (the principle mechanism of tissue repair)?
epithelial regeneration
Suture wound strength is ____% of normal skin. When sutures are removed, strength is _____%. After 3+ months, strength is _____%
70%, 10%, 70-80%
A transudate has __________ hydrostatic pressure and __________ oncotic pressure
increased, reduced
An exudate has _________ vascular permeability
increased
The specific gravity of a transudate is (higher/lower) than that of an exudate
lower
The total protein concentration of a transudate is (higher/lower) than that of an exudate
lower
The protein: fluid/serum ratio of a transudate is (higher/lower) than that of an exudate
lower
The LDH: fluid/serum ratio of a transudate is (higher/lower) than that of an exudate
lower
The glucose: fluid/serum ratio of a transudate is (higher/lower) than that of an exudate
higher
There are (more/less) WBCs in a transudate compared to an exudate
less
What is Virchow’s triad?
- endothelial injury (hypercholesterolemia, inflammation)
- abnormal blood flow (stasis, turbulence)
- hypercoagulability (inherited, acquired)
The most common type of embolus is __________
Deep Vein Thrombosis (affects lungs)
Fat/bone marrow emboli come from __________ and affect ___________
long bone fractures, lungs
10% of maternal deaths occur due to ____________
amniotic fluid emboli
Atheroemboli are caused by __________
atherosclerotic plaque
What is a DIC?
disseminated intravascular coagulation (thrombosis and hemorrhage occurring simultaneously)
What is an infarction?
tissue death (necrosis) caused by vessel occlusion
organs with “white” infarction
heart, kidney, spleen
organs with “red” infarction
lung, liver, intestine
What is cardiogenic shock?
myocardial pump failure (myocardial damage, extrinsic compression, outflow obstruction)
What is hypovolemic shock?
low blood volume (severe dehydration, burns, hemorrhage)
What is the difference between a carcinoma and adenocarcinoma?
carcinoma: epithelial tissue
adenocarcinoma: glandular structure
characteristics of cancer pathobiology
- evading apoptosis
- self-sufficiency in growth signals
- insensitivity to anti-growth signals
- sustained angiogenesis
- limitless replicative potential
- tissue invasion and metastasis
What are the physiologic effects of cortisol?
- carbohydrates:
- protein:
- fat:
- carbohydrates: gluconeogenesis - increased blood glucose
- protein: decreased protein synthesis - increased AA to glucose
- fat: lipolysis - increased free fatty acids
Aldosterone is a __________ that leads to ________
mineralocorticoid, increased Na+ resorption (increased BP)
Cortisol needs a _____ group at the 11 position
-OH
Why do prednisone and cortisone have no topical activity?
they have to go through the liver to convert ketone to hydroxyl
Where does cortisone get activated to cortisol (or prednisone to prednisolone)?
liver
Where does cortisol (or prednisolone) get inactivated?
kidney
How can you treat a mother with GCs without an effect on the fetus?
placental enzyme converts active drug to prodrug
Ratio of glucocorticoid: mineralocorticoid action:
- cortisol:
- prednisone:
- methylprednisolone:
- cortisol: [1:1]
- prednisone: [5:1]
- methylprednisolone: minimal mineralocorticoid action
What is the most potent anti-inflammatory agent?
dexamethasone
T/F: glucocorticoid side effects are unavoidable
true
The risk of osteoporosis from using large cumulative doses of GCs can be decreased by using __________
bisphosphonates
The use of ___________ can reduce peptic ulcers resulting from large cumulative doses of GCs
antacids
Substance P mediates __________ and causes ____________
inflammation, pain
Platelet-activating factor has (local/systemic) effects
local (platelet activating, vasoconstriction, bronchospasms, chemotaxis
Bradykinin is synthesized by the ________ and activated at its site of action
liver
Rheumatoid arthritis: transudate or exudate?
exudate
INFgamma is associated with (acute/chronic) inflammation
chronic (M1 activation)
IL-13 and IL-4 increase production of ______
TGFbeta
Two examples of acute inflammatory cytokines are…
TNF, IL-2
Two examples of chronic inflammatory cytokines are…
INFgamma, IL-12
Delay-activating factor and factor H limit _____ in the complement system
C3/C5 convertase formation
Initial scars are made of type ____ collagen and scar remodeling consists of type ____ collagen
III, I
COX__ is constitutively expressed almost anywhere and COX__ is induced by inflammatory cytokines
1, 2
At low doses, aspirin is COX__ selective and can exert a _________________ effect.
COX-1 selective; anti-thrombotic, cardioprotective
Aspirin has no effect if taken after ____________
ibuprofen (ibuprofen preferentially binds the COX’s, making aspirin incapable of binding them)
What is hyperemia?
an active increase in blood flow due to arteriolar dilation
Examples of transudates include…
- heart failure
- fluid overload
- liver disease
- venous obstruction
Examples of exudates include…
- inflammation
- toxins
- burns
_____________ cells are responsible for vasodilation
endothelial cells (contraction)
Chololithiasis vs. cholecystitis
chololithiasis: hardened deposit within the fluid of the gall bladder
cholecystitis: inflammation of the gall bladder
What are hemorrhoids?
swollen and inflamed veins in the rectum and anus that cause discomfort and bleed
Bronchus undergoes a _________ to __________ metaplasia and the esophagus undergoes a ____________ to __________ metaplasia
columnar, squamous
squamous, columnar
(arterial/venous) emboli affect the lungs
venous
A type of carcinoma with central necrosis and keratin pearls is _______________
squamous cell carcinoma
What types of carcinoma attempts to form glands and occurs in never smokers?
adenocarcinoma
Substance P is associated with … (3)
- pain
- fever
- acute phase reaction
C5 is associated with activation of coagulation factor ____
XII
Rheumatoid arthritis manifests with a ____________
an exudate
Are lipoxins chemotactic?
no
IL-4 and IL-13 associating with macrophages is likely to induce increased _________ production
TGFbeta
Neovascularization, fibroblast proliferation, and macrophages constitute _________ tissue response
granulation
What are some common causes for defective leukocyte function?
- acquired: chemo, diabetes
- inborn genetic defect
What do macrophages do during chronic inflammation?
- ingest microbes
- initiate tissue repair
- secrete inflammatory mediators
- present antigens to adaptive immune system
Aspirin is COX__ selective at low doses
COX1 (cardioprotective)
effusion
extravasation of fluid into (usually natural) spaces
Can a red or white infarct be re-perfused?
red
cavitary
direct seeding of body cavities or surface (i.e.: ovarian cancer)
