Term
1) Thrombus is red due to entrapped ____________.
2) The Lamination varies depending on these two factors.
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Definition
1) erythrocytes
2)
What is The composition of the thrombus and the rate of blood flow while the thrombus was forming |
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Term
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Definition
| keeping blood confined to cardiovascular system |
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Term
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Definition
| example of deficient immune defenses, and susceptibility to infections |
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Term
| Learn about the different types and subtypes of HIV. |
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Definition
HIV-1 Type: in humans, likely transmitted early 1900s
HIV-2 Type: low load, slow, limited in humans
B Subtype: Most common in America, Europe, Australia
Subtype C: Heterosexual
Subtype D: faster, more virulent |
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Term
| Understand the current epidemiology of HIV both worldwide and in the U.S. |
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Definition
Total 33 million
US 1.5 million
Total 2009 New 2.6 million
US 56,300
Africa life expectancy at birth has gone down sig since 1970
AIDS death 2009 1.8 million |
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Term
| Understand the means of HIV transmission. |
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Definition
African American, Male-Male, Injection of Drugs, perinatal as well;
circumcision reduces rates 50-70%
Binding to CD4 HIV-1 particle
Reverse Transcription
DNA
Enters Nucleus, Transcription/Translation
RNA (High Mutation/Replication Rate)
Assembly |
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Term
| Understand the basics of viral pathogenesis and the clinical parameters of HIV infection. |
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Definition
High Mutation, High Replication
leads to CD4 Depletion
Clinical --
50-70% experience mononucleosis-like, self-limit
Acute infection: high viral load; variable CTL response during symptoms
CTL response lowers Viral load to set point
Chronic Phase of HIV-1 infection:
Asymptomatic (clinical latency) but virus replicatin in peripheral lymph
Lymphoid tissue is altered; virus goes UPPP; Collapse of HIV-1 Immune response (CD4 goes DOWNNNN) -- opportunistic diseases ensue...
after a few years...AIDS
Acquired Immunodeficiency Syndrome |
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Term
Learn the current status of combination antiretroviral therapy.
Currently approved agents
Indications for treatment
Pros and cons of treatment
Use of resistance tests |
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Definition
CD4 levels (immunologic status) has been kept up by Zidovudine therapy -- but it was shown that this isn't best marker of survival of patients...
****HIGH viral load and LOW CD4 count together give good indication of progression to AIDS
HAART (highly active anti-retroviral therapy)
1985-1997 substantial increase CD4 and decrease in Viral RNA numbers; first by monotherapy (targeting a specific type), then Double RT Combinations, then even more with HAART (include RT's NA's Integrase Entry)
don't allow things to replicate
limit the replication -- acheive UNDETECTABLE levels of Virus in serum
---further prevents mutations
If patient has poor adherence to therapy -- more resistance(mutations) -- drug fails
Current question mark: If patient isn't showing AIDS symptoms, and he or she has a HIGH CD4 count -- controversial if treatment is necessary... |
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Term
| Learn the complications of late stage HIV infection |
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Definition
Risk of opportunistic infections goes up as CD4 goes down
HAART has increased CD4 counts (less being killed off by RNA germ line infection) and lowered Viral RNA load
AIDS indicators
Candida
Cervical cancer (invasive)
Coccidiosomycosis (extrapulmonary)
CMV other than liver, spleen
HSV visceral
Histoplasmosis (extrapulmonary)
HIV dementia, wasting
Lymphoma
Mycobacterium avium (disseminated, not under control)
M tuberculosis
Pneumocystis jirovecii
Pneumonia (recurrent bacterial)
PML
Salmonella septicemia
Toxoplasmosis of internal organ |
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Term
| Discuss how an infectious protein agent (prion) replicates |
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Definition
Prion properties
resistant to inactivating factors like UV, ionizing radiation, heat, formalin (Scrappie has NO reduction in Activity, even with VERY high UV dose)
No Nucleic Acid found in them yet
Sensitive to hydrolyzing or modifying proteins (sensitive to denaturing agents)
--so it is basically a replicating protein, derived from normal cellular protein PrP C (harmless alpha helices until it becomes Abnormal PrP SC (beta sheets))
Abnormal Protein PrP SC (Prion)
--causes other proteins to fold abnormally
--becomes protease resistant
--aggregates
--associated with diseases
how are abnormal proteins aquired?
-sporadic, somatic mutation, germ line inheritance, infections, contaminations |
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Term
| Discuss how prion disease can be sporadic, inherited, and acquired |
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Definition
Like a really SLOW virus...1-30 yr incubation
Fatal, No immune response, Abnormal Protein PrP Sc in CNS
Example: Transmissible Spongiform Encephalopathy (TSE)
- Scrappie (18th century, sheep, contaminated vaccine)
- Kuru (1950's Canabalism, dementia)
- Creutzfeldt-Jakob Disease (CJD) (1920, neurogenative, Ashkanazi Jews)
---Sporadic (most common CJD, sCJD)
---Iatrogenic Infectious CJD iCJD (medical procedures, HGH treatment)
---Genetic CJD
---GSS genetic subclass of CJD; infectious
---Fatal Familial Insomnia FFI |
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Term
| Outline how mad cow disease arose. |
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Definition
BSE Bovine Spongiform Encephalopathy
Mad Cow Disease
1980's United Kingdom; animals fed other sheep CNS
Prion survives any type of heating/cooking
neural/motor condition; nerves, brain
BSE also crosses and forms a "NEW variant of CJD" in 1996 |
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Term
| Discuss the origin of the species barrier in prion transmission. |
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Definition
Mad Cow to Humans (BSE to vCJD)
Prions usually have restricted host range, e.g., scrapie is not known to have passed onto humans
When prions do cross over; incubation period is longer |
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Term
| Discuss the mechanisms of prion strain variation. |
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Definition
could represent the different folding and/or assembly states; conformational differences, different aggregations states
Different stains have different disease manifestations and affect different regions of the brain
I.e. CJD, FFI --cerebrum; vCJD, Kuru, GSS --cerebellum |
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Term
| Outline the potential ways to prevent and treat prion disease |
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Definition
prions can be found -- blotting
PMCA like PCR -- seeding, amplification
treatments
1. Eliminating normal PrPC may prevent disease
1). RNA interference?
2). Other ways to block PrPC expression
2. Prevent the conversion of PrPC to PrPSc:
1). Targeting PrPC
“Neutralizing” antibody (but auto-immunity?)
Soluble dimeric PrPC
2). Targeting modulating factors? (factor X?)
Manipulating cytokines?
3. Destabilize PrPSc |
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Term
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Definition
| Injured endothelium exhibits procoagulant activity |
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Term
| dysfunctional platelets (most common causes are |
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Definition
| medications (aspirin, plavix) |
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Term
| plug and clot formation steps |
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Definition
Vasoconstriction
vWF proteins line the broken vessel wall
Platelets adhese to the vWF at the site of injury
Platelets aggregate and release procoagulant
Coagulation occurs
Extrinsic pathway (7a activates factor 10)
Intrinsic pathway (12a activated)
11,9,10 activated
Common Pathway
--formation of Fibrin Clot
Clot is reslut of aggregation of platelets, coagulation cascade/clotting factors
unable to form the plug because of
Vit K deficiency
Liver disease
Warfarin therapy
Check for Platelet count
PT test and PTT test ---if both are effected, there is a problem in the Common pathway; if PT is effected, think factor 7 |
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Term
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Definition
because of immobility, pill, smoking,
CANCER association with V. Thrombosis; Trousseau Syndrome |
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Term
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Definition
HIT syndrome in patients on Heparin Therapy (for anti-coagulation)
a platelet factor 4 complex forms, induces Antibody, platelets, and more clotting
How to recognize it?
Platelet count will drop --important to watch platelet count |
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Term
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Definition
red -- hemorrhagic
white -- ischemic |
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Term
| gross time frame of infarct |
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Definition
paleness 1-2 days
yellow with red around it 3-4 days
gel 1 week
collagen 1-2 weeks |
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Term
| histological progression of infarct MC |
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Definition
few wavy fibers .5-4 hr
eosinophils 4-12 hr
necrosis of myocytes 12-24 hr
HEAVY PMNs 1-3 days
Macrophages 3-7 days
fibrosis
collagen 2-8 wks.
scar (ghost) >2 mo. |
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Term
| Severity of MI and significance depend on |
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Definition
Vasculature
Occlusion developing-rate
Sudden cut-off by thrombosis
Or tumor slowly cutting it off
Hypoxia vulnerability
Oxygen in blood |
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Term
Hemo Disorders lecture
Bioterrorism
Aging |
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Definition
| skim through lecture slides |
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