Mini 2 - Fund 2 pt.2 Flashcards
1
Q
What is the difference between ‘curing’ and ‘healing’?
A
Curing is eliminating disease, healing is restoring wellness.
2
Q
What are the two models of health and disease?
A
Biochemical/naturalist model or Normative model.
3
Q
Where do the PNS and SNS originate from and what’s the length of the preganglionic fibers?
A
PNS: craniosacral and long
SNS: thoracolumbar and short
4
Q
How is choline brought into the axoplasm?
A
With a sodium dependent carrier. This is the rate dependent step in ACh synthesis.
5
Q
Where does AChE vs BuChE function?
A
AChE in cholinergic neurons, NMJ, erythrocytes
BuChE in plasma, liver
6
Q
Where are M1-M3 found?
A
All in CNS neurons.
M1 and M3 found in ganglionic neurons, presynaptic terminals, M2 also found in myocarsium and some smooth muscle.
M3 found in smooth muscle, exocrine glands, vascular endothelium.
7
Q
How are dopamine, norepinephrine, and epinephrine produced?
A
Tyrosine actively transported to the axoplasm and then is hydrolyzed by Tyr hydroxylase to DOPA (rate limiting step).
Then L-aromatic AA decarboxylase decarboxylates it to dopamine.
In the storage vesicles, it is transformed to NorE by DA-beta-hydroxylase.
NorE is converted to E by phenyl ethanolamine N-methyltransferase (has glucocorticoid cofactors).
8
Q
What are MAO and COMT?
A
Catecholamine metabolizers.
MAO found in the mitochondria of neurons, liver, kidney cells and has low substrate specificity. MAO-A preferentially oxidizes indoleamine, MAO-B preferentially oxidizes phenylethylamines.
COMT is located in the cytoplasm of many cells but is relatively scarce in adrenergic neurons - has high substrate specificity.
9
Q
How are intraneural and extraneural E/NorE metabolized and what are the final metabolites?
A
Intraneural ones are first deaminated by MAO and then methylated by COMT, extraneural do the reverse order.
Final metabolite is vanillylmandelic acid.
Final metabolite of dopamine is homovanillic acid.
10
Q
Where are D1 and D2 receptors found beyond CNS neurons? What type of receptor are they?
A
D1 is found in vascular smooth muscle (renal and mesentaric) and D2 is found in some presynaptic terminals.
D1 is G2, D2 is Gi.
11
Q
What is an organic vs a functional neuropsychological abnormality?
A
Organic - structural cerebral or systemic medical pathology.
Functional - psychological or emotional medical pathology.
12
Q
When is neuropsychological testing not appropriate?
A
In a period of detox or in an early period of drug abstinence.
13
Q
How are ADDs generally diagnosed?
A
Neuropsychological testing not necessary - generally through careful history, structured clinical interviews, rating scales (ratings obtained mostly from parents or teachers).
Common rating scales: Connors rating scale, ADHD symptoms rating scale, Achenbach child behaviour checklist.
14
Q
What is the MMPI?
A
Used for assessing psychopathology - answers given as true, false, cannot say - interpretation is driven by patterns of elevations or depressions of scales.
Can be used to screen for substance abuse problems, can help understand how patients are psychologically affected by medical problems, can provide information for how patients are likely to respond psychologically to medical interventions.
15
Q
What are the Wechsler Intelligence scales?
A
To judge intelligence (capacity to act purposefully, think rationally, and deal effectively with their environment).
WPPSI (3-7years, 3 months)
WISC (6-16yrs, 11 months)
WAIS (16-89)
Each scale provides verbal IQ, nonverbal/performance IQ, full scale IQ (each has mean 100 and SD 15).
WAIS used in military placement, mental deficiency .
16
Q
What are the Wechsler Memory Scales?
A
Used to assess memory and learning in 16-90.
Immediate memory (auditory/visual), General/delayed memory (recognition), working memory
17
Q
What is endotoxin?
A
Lipid A - highly conserved (PAMP).
18
Q
What does pyrogen-free mean?
A
No LPS.
19
Q
What is the main role of the O-antigen?
A
Immune evasion (host mimicry, variation, serum resistance).
20
Q
How does the LPS trigger immune response?
A
LBP will bring it to TLR complex, which will trigger a signalling cascade and macrophage activation. THe macrophage will do things, activate cytokines.
21
Q
Describe the symptoms of endotoxic shock.
A
Lipid A response. Hypotension, DIC, multiorgan failure, death.
22
Q
How are bacterial capsules visualized?
A
Negative staining (methylene blue, maybe india ink), fluorescent antibodies.
23
Q
How do bacterial capsules trigger immune response?
A
T-independent B cell activation. The capsule is a repetitive molecule - binds multiple BCRs, activate and get mostly IgM. Soluble IL-4 can aid in proliferation and IgG1 switch.
24
Q
How do capsules prevent immune killing of the bacteria?
A
Difficult to penetrate, thick (block receptor binding), often acidic/negatively charged - repel phagocytes.
Some can reduce complement activity - sialic acid binds Factor H (destroys anything complexed with C3b).
25
What are biofilms? What are the phases of bacteria in a biofilm?
Micro/macrocolonies of bacteria surrounded by matrix of bacterial extrapolymeric substances (EPS) and environmental components (e.g. fibrin).
Most bacterial infections involve biofilms.
Reversible attachment, irreversible attachment, maturation 1 and 2, dispersion.
Cells inside the biofilm are slow growing, have activated stress tolerance genes.
26
What are superantigens? Give examples.
A type of exotoxin. Links MHCII and TCR in absence of specific Ag (nonspecific T cell activation). Normal signalling cascade in abnormally large number of cells.
Staph. aureus - Staphylococcal enterotoxins, TSSTs.
Streptococcal pyrogenic toxins.
27
What are cytolysins? Give examples.
A type of exotoxin. Pore forming toxins insert into the membrane, oligomerize and form pores. S. aureus alpha toxin.
Phospholipases are a type of cytolysin. CLostridium perfringens alpha toxin is one.
28
What are AB toxins? Give examples.
A type of intracellular exotoxin.
A domain is active (toxic anzymatic activity), and B domain is the binding domain (induces endocytosis).
Diptheria toxin - A subunit ADP ribosylates the dipthamide residue on EF2.
Vibrio cholerae 'cholera' toxin - A:5B form, A ADP-ribosylates a Gs, resulting in excess PKA, causing too much CFTR activation.
29
Describe bacterial injected toxins.
A type of intracellular exotoxin. Injected via a type III/IV secretion system. Often has cytotonic effects, changes surface/shape of the cell.
Many will have some kinase activity.
30
Describe Neisseria meningitidis generally.
"Meningococcus". 1st/2nd most common cause of bacterial meningitis. Can cause sepsis 'meningococcemia'. Encapsulated.
Human nasopharynx is its only source - transmission via respiratory droplets or direct contact. Efficient transmission - up to 80% of people in contact with an infected person become carriers. Invasion most common when exposed to new strains (start attending school, go off to live in a dorm, etc.)
31
Describe the capsule of Neisseria meningitidis.
Capsule helps it survive in the bloodstream - 12 serogroups exist based on capsule structure. B, C, Y, A, W-135 most commonly cause serious disease.
32
What is the mortality rate of meningococcal sepsis?
100% untreated, 10-15% treated.
33
What is Waterhouse-Friderichsen's syndrome?
Adrenal gland failure that may occur in fulminant meningococcal sepsis.
34
What are the major virulence factors of Neisseria meningitidis?
Type IV pili (coloinze), IgA protease (colonize), OM proteins (invade), Capsule, LOS (produces LOS while alive/intact/growing - blebs - so make a lot more than others).
35
What skin signs can you see in meningococcal disease?
Mottling, petechiae that can progress to purpura.
36
Describe the capsule vaccine to Neisseria meningitidis.
Quadrivalent to capsule W-135, Y, A, and C.
Recently a protein-based vaccine against the B serogroup has come out.
37
What is a distinguishing feature of Pseudomonas aeruginosa infection?
Fruity odour, pigmented visibly blue or green, pus can be coloured.
38
What are the virulence factors of Pseudomonas aeruginosa besides exotoxins?
Endotoxin, adhesins, biofilm (associated with chronic infection), degradative enzmes, pyocyanin (forms ox. rads, is responsible for pigmentation).
39
List all the Pseudomonas aeruginosa exotoxins.
Exotoxin A, Cytolysins (PLC, Leukocidin) Type III exotoxins (ExoS, T, U, Y), Exoenzymes (Elastase, alkaline protease).
40
Describe Pseudomonas aeruginosa exotoxin A.
AB toxin - A subunit acts in same was as diptheria toxin, binds macroglobulin receptor LRP1.
41
Describe P. aeruginosa ExoS and ExoU.
ExoS alters cell shape, prevents DNA synthesis.
ExoU is a phospholipase - associated with more fulminant, virulent diseas.
42
Describe P. aeruginosa exoenzymes.
Facilitate spread through tissue. Elastase can do so through lung and can also cause ecthyma gangrenosum (hemorrhagic skin lesions). Alkaline protease can damage tissue and immune cells.
43
How do you tell if biofilm in a P. aeruginosa infection is mature/late or early?
Late if has Alginate "mucoid polysaccharide". Linked to severe disease an dissemination.
44
What type of immunity are IgGs and IgAs good for?
IgGs are good opsonizing Abs, IgAs are good for mucoid immunity.
45
Describe passive immunization and the types of passive immunization.
Injection of purified Abs or Ab-containing serum into recipient. Rapid, temporary (weeks-months) immunity, gamma-globulin/immunoglobulin is a mix of plasma proteins and broad spectrum of Abs (mainly IgGs) obtained from different donors. Given for disease prevention.
Hyperimmune human Ig preparations have high concentration of antibodies specific for a aprticular pathogen or toxin - given post exposure.
46
Which pathogens have post-exposure hyperimmune human Ig preparations available?
HepA, HepB, Measles, Rabies, Chickenpox, CMV, Tetanus (human/equine), Botulism (equine), Diptheria (equine).
47
What are the cons of inactivated vaccines and what sort of agents is it used for? What are the types?
Immunity not life-long, may be only humoral (not cell mediated), local IgA response not elicited, booster shots required.
Used for agents that cannot be attenuated, may cause recurrent einfection, or have oncogenic potential.
Killed, Subunit (polysaccharides can only drive T-cell independent B cell responses - IgG switching only, limited affinity maturation, waning titers after a few months, poor protection to kids under 18 months), Toxoid.
48
What is a hybrid virus vaccine?
A type of live vaccine where genes from an infectious agent is put into a virus of low virulence.
49
What are DNA vaccines?
The gene for the protein that elicits the protective response is cloned into a bacterial plasmid that allows for expression of the protein by a human cell - naked DNA is inserted into the muscle or skin and enters the host cell.
They're good for agents needing T and B cell responses but aren't appropriate as live vaccines - like HIV and plasmodium falciparum.
50
What are adjuvants?
A substance that enhances the immunogenicity of antigens. Stimulate APCs (particularly DCs), slow release of Ag to help sustain immune response long enough for effective immunity to develop.
51
Name the adjuvants in use in the US.
Aluminum salts and gels (only ones in use in Canada), MF59 (oil-in-water emulsion of squalene oil), CpG 1018, A501B (monophosphoryl lipid A and QS-21).
52
What is a culture?
Sum total of knowledge passed generation to generation in any given society. Includes ideas about illness and healing, exists as an adaptation to or coping with the human condition.
53
What is an explanatory model?
The way a person explains the cause of illness - why it occurred, what course it'll take, what treatments are appropriate.
54
Describe some characteristics of anaerobes.
Lack cytochrome oxidase, reduced/absent detoxification of ROSs, prefer/need low redox potential (Eh/Eo). Many genera ferment acids/alcohols.
55
What detoxifies ROSs better, an aerobe or a microaerophile?
Aerobe.
56
How does a facultative anaerobe generate energy?
Aerobic respiration, fermentation, maybe anaerobic respiration.
57
How do aerotolerant and strict anaerobes generate energy?
Only through fermentation.
58
Rank a facultative, aerotolerant, and strict anaerobe in terms of who detoxifies better.
Fac > aerotol > strict
59
What are some sites with normal anaerobic flora?
GI (colon they are 1000x more than aerobic), GU, oropharynx.
60
Describe Actinomyces.
Gram(+) anaerobe. Filamentous branching rods. Normal in URI, GI, GU. Pyogenic (pus contains yellow granules made of bacteria and neutrophils 'sulfur granules').
61
Describe Lactobacillus.
Gram(+) anaerobe. Normal in oral, GI, GU, common probiotic/rare pathogen.
62
What are some general characteristics of gram(-) anaerobes?
Often fastidious, slow-growing, stain poorly.
63
Describe Prevotella and Porphyromonas.
Gram(-) anaerobes. Very small rods, black colonies.
64
Describe Fusobacterium.
Gram(-) anaerobes. Elongated rods, pointy 'fusiform'.
65
Describe Bacteroides spp.
Gram(-) anaerobe. Slender rods/coccobaccilli (can look mixed).
Grow quick on blood agar, bile resistant, hydrolyze esculin, SOD(+), catalase (+).
Antibiotic resistance common. Virulence factors: pili, polysaccharide capsule. Lipid A not very pyrogenic.
66
Describe Bacteroides fragilis.
Gram(-) anaerobe. Most commonly isolated organism in intraabdominal infections/abscesses. BFT toxin (metalloprotease, degrades E-cadherin, stimulates fluid loss in intestine, IL-8 production, oncogenesis(?)).
67
How do IC bacteria get into cells? Name some examples for the methods.
Phagocytic cells - via phagocytosis (PAMP recognition).
Nonphagocytic cells: Zipper mechanism (tricks host cell into wanting to adhere via adhesin expression) (Listeria, Yersinia, Campylobacter, Helicobacter).
Trigger mechanism (hijacks cytoskeleton - bacterial type III/IV secretion system injects effectos into host cells which stimulates actin and other cytoskeletal components to form protrusions/endocytic vesicles) (Salmonella, Shigella, Chlamydia).
68
Name the obligate intracellular bacteria.
Rickettsia, Orientia (vacuolar - stay in phagosome, prevent lysosome fusion), Chlamydia, Chlamydophilia, Ehrlicia, Anaplasma, Coxiella, some mycobacteria (cytosolic/nuclear).
69
Can Orientia and Rickettsia make ATP?
Yes, or they can steal the host's.
70
What are the two forms of vacuolar intracellular bacteria?
Reticulate body - metabolically active, non infectious, forms inclusion body, fragile.
Elementary body - inactive but infectious; tough.
71
What's special about Chlamydia and Chlamydophilia?
Protein cell wall, don't make ATP, don't make NAD.
72
Legionella pneumophilia - describe its morphology, characteristics, growth requirements, reservoir, and what diseases it causes.
Gram(-) rod (may be more coccobacillary in tissue), poorly staining (can stain with Dieterle silver), thin, motile, non-fermentative, oxidase(+), catalase(+), only uses AAs, needs BCYE agar (L-cys, Fe3+, oxygen), slow growing 2-5d.
Reservoir is amoebae in freshwater, causes atypical pneumonia (Legionnaire's), Pontiac Fever - in immunocompromised hosts.
73
Describe infection and pathogenesis with Legionella pneumophilia. How is it diagnosed?
Inhaled, wants to be in macrophages (can also infect alveolar epithelial cells and monocytes). OMPs bind alveolar macrophage complement receptors via C3b or directly. Several surface proteins including Mip (macrophage infectivity potentiator) enhance phagocytosis).
Once in, type IV secretion system secretes enzymes that hijack vesicle trafficking/ Phagosome recruits the ER which prevents lysosome fusion. This causes apoptosis.
It's diagnosed with urine antigen but only detects the most common serotype.
74
What is the morphology of Listeria monocytogenes?
Gram(+), weakly beta hemolytic, nonspore forming rod, can tolerate salt and pH extremes, replicates at 4Celsius. Catalase (+). Distinctive tumbling motility.
75
How is Listeria monocytogenes taken in and what can it cause?
It is ingested through contaminated food. It can cause sepsis, meningitis. Primarily in immunocompromised hosts.
It can cross the placenta.
76
What is the pathogenesis of Listeria monocytogenes?
Enters phagocytes by phagocytosis, non phagocytes by Zipper mechanism. Internalin A binds E-cadherin, Internalin B binds c-Met.
The drop in pH activates 2 PLCs and listeriolysin O (LLO) - pore forming toxin. It escapes into the cytosol and then surface protein ActA polymerizes actin at one pole and pushes it along.
77
Describe the morphology and growth requirements of Coxiella burnetti. What illnesses does it cause and how is it transmitted?
Microaerophile, gram(-) but stain poorly, need BL3 lab to culture.
Causes Q fever (interstitial pneumonitis) via inhalation of particles or zoonosis.
78
Describe the pathogenesis of Coxiella burnetti.
Small cell variant (SCV) is resistant, inert environmental form (stealth pathogen). Binds macrophage integrin involved in apoptosis, not surface receptor for pathogens, Lipid A acts as TLR4 antagonist.
Endosome acidifies, it activates into LCV/CCV (Coxiella-containing vacuole). Survives phagolysosome, injects proteins to delay apoptosis via type IV secretion system.
79
How do you determine if something is a HAI/nosocomial infection?
Appears at least 48 hours after admission or less than 48 hours after discharge.
80
What does 'iatrogenic' mean?
Infections caused by physician (includes healthcare measures in general).
81
What makes up 85% of nosocomial infections?
UTI, SSI, pneumonia, BSI, GI, CDAD.
82
What are the most lethal HAIs?
Pneumonia, bacteremia.
83
What are the Universal/Standard Precautions:
Handwashing, PPDs when contact with body fluids is anticipated, cough etiquette, safety precautions, limiting surfaces touched.
84
What are contact precautions? What organisms necessitate them?
Standard precautions + private room, gloves/gowns upon entry and in transport, clean hands between tasks, dedicated equipment.
C. diff, antibiotic-resistant organisms, avial influenza, chicken pox, SARS, others.
85
What are droplet precautions? What organisms necessitate them?
Standard precautions + private room/cohorting, mask and eye protection within 3/6-10 feet of patient, mask patient if must leave room, clean hands between tasks.
Meningococcal meningitis, mycoplasma pneumoniae, diptheria, others.
86
What are aerosol precautions? What organisms necessitate them?
Standard precautions + negative pressure private closed room with air exhausted through HEPA filter or outdoors (AIIR), closed door, N-95 required to enter, mask patient out of room, controlled entry to visitors/personnel, notification.
Avian flu, pulmonary TB, measles, VZV, smallpox, SARS, monkeypox.
87
What is positive pressure vs negative pressure isolation?
Negative pressure isolates infectious patient, positive pressure provides source of isolation for non-infections, at risk patients.
88
What does decontamination mean?
Prevent microorganisms from reaching susceptible site in sufficient numbers.
89
What is Sterilization and what are the general methods?
Destruction of ALL living things and viruses on fomites. Done through heat, irradiation, filtration, or chemicals.
90
Describe heat sterilization.
Autoclave, oven, steam (121C, 15psi, 15min), or dry hear (170C, 60min).
91
Describe chemical sterilization.
Ethylene oxide most common, plasma (H2O2) gas (treated with free rads), Formaldehyde, Glutaraldehyde (irritant, smellhy, carcinogenic), Peracetic acid.
92
What is disinfection?
Destruction/inactivation of MOST viable organisms. Of they won't kill spores = germicides.
93
Describe high-level, internediate-level, and low-level disinfectants.
High: Kills/inactivates all but high spore loads (HOCl, low levels of chemical sterilants, less heat, aldehydes, O2-based, some halogens).
Intermediate: Kills vegetative bacteria, some viruses, some fungi, a few can kill mycobacteria - usually need high (Iodophors, alcohols, phenolics).
Low: Kill vegetative bacteria, some viruses - enveloped/larger size -, some fungi (quaternary ammonium compounds, triclosan).
94
What are antiseptics? Give examples
For disinfecting live tissue - cannot kill spores.
ALcohols, Chlorhexidine, Iodophors. Some (e.g. betadine) can kill mycobacteria but must cannot.
95
Describe pasterurization and ultrapasteurization.
72Celsius for 15-20s - kills most pathogens, reduces bacterial loads, will be stable 2-3 weeks if cold.
135Celsius for 2s - will kill spores, if in aseptic packaging, wll be stable 6-9mo at room temperature.
96
Describe the Spaulding scheme.
Critical items: breach barriers, enter sterile sites, require sterilization.
Semicritical items: Contact broken skin/mucous membranes, sterilization or high-level disinfection required.
Noncritical items: Contact intact skin only, mid/low level disinfection usually OK.
97
What disinfectants kill by membrane leakage?
Phenolics, quaternary ammonium compounds, chlorhexidine.
98
What are intermediate/locally malignant tumours?
Locally invasive but do not have the tendency to metastasize.
99
What is carcinoma in situ?
Pre-invasive cell proliferation (severe dysplasia) that has cytological features of malignancy.
100
Why does a neoplasm grow faster than normal cells?
Because of inhibition of apoptosis and retention of cells in the cell cycle.
101
WHy are slow growing cancers resistant to chemo?
Because chemo targets cells that are actively in the cell cycle.
102
What are some microscopic differences between benign and malignant tumours?
Benign ones are always differentiated, malignant aren't. Both can have tissue atypia, only malignant will have cellular atypia/pleomorphism.
103
What is desmoplasia/schirrous cancer?
An increase in stromal volume - type of tissue atypia.
104
What is anaplasia?
Complete lack of differentiation.
105
What is the most common type of cancer and when does mortality for it peak?
Carcinoma. 55-75.
106
What kind of cancers predominate in young adults?
Leukemia, lymphoma, CNS and soft tissue tumours (sarcoma).
107
What kind of cancers predominate in children?
Acute leukemia, blastomas, hepatocellular carcinoma, soft tissue tumours (rhabdomyosarcoma).
108
What are the most common cancers in males in the US?
Prostate - 24% (death 10%), Lungs/Bronchi - 14% (death 28%), Colon/Rectum - 8% (death 8%)
109
What are the most common cancers in females in the US?
Breast - 29% (death 15%), Lungs/Bronchi - 13% (death 26%), Colon/Rectum - 8% (death 9%)
110
What are some genetic/acquired predispositions to cancer?
Chronic inflammation (either via ROS production/DNA damage or metaplasia/hyperplasia of repair with possible neiplastic transformation), Precursor Lesions (carcinoma in situ is most severe form, occupies entire thickness of tissue), Immunodeficiency.
111
What are the types of local tumor growth?
Expansive (compresses surrounding tissue with formation of fibrous tissue capsule - feature of benign tumours)
Invasive/Infiltrative - invades other tissues (malignant)
112
Describe carcinoma.
Classical invasive growth with crab-like sprouts, starts with penetration of BM. Carcinoma with microinvasions is a cancer with a relatively good prognosis.
113
What is exophytic growth?
Malignant neoplasm projects out from epithelial surface and also grows down and penetrates BM.
114
What are the routes of metastasis?
Lymphatogenous, hematogenous, perineural, seeding of body cavities/surfaces/spaces.
Lymphatics typical for carcinomas and some sarcomas.
115
Describe hematogenous spread of cancer.
Venous wall more permeable so generall follows venous flow. First wave is lungs for systemic circulation, liver for portal.
Next waves are bones, bone marrow, brain, adrenals, liver (from systemic).
All sarcomas do this, all advanced carcinomas, some early carcinomas.
116
What kind of cancers spread perineurally?
Prostate and pancreas carcinoma.
117
What kind of cancers spread by seeding of body cavities?
Malignant tumours of CSF (CSF spaces), Urothelial carcinoma of renal pelvis along natural passage - ureter and urinary bladder, Krukenberg tumour along peritoneal and pleural cavities.
Krukenberg tumour is a bilateral ovary-located metastasis of gastric and colon mucus-producing adenocarcinomas.
118
What are some effects of malignant cancer only?
Cachexia (proteolysis-inducing factor by tumorous cells, TNF and IL-6 production by tumour infiltrating immunocompetent cells), paraneoplastic syndromes.
119
Name some paraneoplastic syndromes.
SIADH - small cell lung carcinoma
Cushing's (ACTH) - Small cell lung carcinoma
Polycythemia - renal cell carcinoma
120
Which grows faster, carcinoma or sarcoma?
Sarcoma.
121
What are the structures of carcinoma vs sarcoma?
Carcinoma - cells arranged in groups, well-formed stroma.
Sarcoma - cells arranged in diffuse sheets, poorly-formed stroma.
122
What are the metastasis differences between carcinoma and sarcoma?
Carcinoma - early lymphatic meta, late blood-borne meta,
Sarcoma - lymphatic meta uncommon, early blood-borne meta.
123
How is the level of tumour malignancy determined? Which has greater clinical value?
Grading (aggressiveness) and staging (size/spread).
Staging has greater clinical value.
124
Describe tumour grading.
Degree of differentiation (determined by resemblance to normal tissue prototype, 1 better than 2, 3, anaplastic carcinoma).
Growth rate (#mitoses/HPF)
Cellular atypia (pleomorphisms (cellular and nuclear), multinucleation, atypical mitoses).
125
Describe tumour staging.
Evaluation of size of primary lesion, extension to adjacent tissues/organs, spread through regional LNs, presence/absence of distant metastases
TNM system (T1->T4 is increasing size, N0->N3 is LN involvement, M0/M1 is presence of metastases.
AJC(C) system stages 0-IV.
126
How do you know if you should report something to the CDC?
Needs to answer 2 of
Is the public health impact of the event serious?
In the event unusual or unexpected?
Is there a significant risk of international spread?
Is there a significant risk of interational travel and trade restrictions?
127
What is the difference between a condition/incident being reportable and notifiable?
Reportable is mandatory to report and is done with personal identifiers, notifiable is voluntary and has no personal identifiers.
128
What does it mean when something is immediately notifiable, extremely urgent, urgent, and routinely notifiable.
Immediately, extremely urgent - call CDC within 4 hours and submit electronic case notification by next business day (anthrax, botulism, plague, smallpox).
Immediately, urgent - call CDC within 24 hours and submit electronic case notification in next regularly scheduled electronic submission (measles, rabies, yellow fever).
Routinely - submit electronic case notification within next reporting cycle (HIV, Lyme disease).
129
What are the symptoms of shaken baby syndrome?
Retinal hemorrhages, floppy body/extremities, increased head size, subdural hematoma.
130
What can get your license revoked?
Conviction of a crime, unprofessional conduct, personal/professional incapacity.
131
What is the Tarasoff exception to the right to privacy?
Duty to warn and duty to protect - can break confidentiality if reasonable identifiable victim and patient believed to actually possess risk of inflicting serious bodily injury
132
What is capacity vs competence?
Capacity = ability of a patient to make a specific decision at a specific time (medical question)
Competence - mental ability to make decisions/perform acts for which the person is legally responsible/accountable for.
All adult patients are assumed to be competent/
133
What may a mature minor seek out medical treatment for without parents?
Drug/alcohol abuse, VD, contraception, pregnancy.
134
What judgments do you use if the patient is incompetent?
Subjective standard (advance directive) - most recent carries most weight, Substituted judgment (someone who knows patient well), or Best interest/reasonable-person standard.
135
What is the difference between root cause analysis and failure mode and effects analysis?
Root cause analysis is a method to analyze serious ADEs to identify the direct cause of errors PLUS contributors.
Failure mode and effects analysis is done BEFORE an ADE to identify the effect of a potential failure, break down the process
136
What is the viral prodromal phase?
Innate immune response, non-specific systemic symptoms.
137
How does IL-10 affect the immune system?
Turns off Th1 response.
138
What is virulence?
Capacity of an infection to cause disease (measured by incidence or by disease severity).
139
What is the NSP4 enterotoxin?
Rotavirus protein that inhibits glucose-coupled Na+ transport and leads to diarrhea.
140
What is gp41?
HIV protein that causes CD4 apoptosis.
141
What are IFN alpha, beta, gamma?
Made by immature Dcs and virally infected cells in response to polycistronic ssRNA or dsRNA.
Puts cells into antiviral state.
142
Describe antiviral state.
IFN triggers own cell (and others) to synthesize Pkr.
dsRNA activates 2 Pkrs (dimerizes) and inactivates eIF2. Apoptosis.
IFN also triggers RnaseL synthesis. RnaseL is only activated with 2'5'oligoA synthetase, which needs dsRNA to bind so 2'5'adenylic acid can be made to activate RnaseL and trigger apoptosis.
143
What is Us11?
HSV1 protein that blocks Pkr.
144
How can Abs neutralize viruses?
Can do uncoating inhibition of naked virus, VAP block on enveloped, activate MAC, form immune complexes (C3b binds, CR1 binds on RBCs).
145
What is ERBB2?
AKA HER2.
A GF receptor, a mutation can amplify. Breast cancer can be treated by blocking ERBB2.
146
What is the common mutation in Neurofibromatosis type I?
Neurofibromin1 (a GAP - Ras inactivator).
147
What is the mutation in CML?
t(9;22) ABL + BCR.
148
What is Gleeves/imatinib?
Neutralizes ABL-BCR kinase activity in CML.
149
What is the APML (acute promyelocytic leukemia) mutation?
t(15;17) PML-RARA.
RARA alpha is a retinoic acid mutation, stimulates cell differentiation. PML-RARA has low affinity and so retinoic acid in physiologic dose causes APML.
150
What is the Burkitt Lymphoma mutation?
t(8;14) C-MYC over expression.
151
What is the result of N-MYC overexpression?
Neuroblastoma.
152
What is the G1/S checkpoint and what inhibits it?
Cyclin D-CDK4.
p16 (INK4A), p15, (p18, p19)
153
What is the S phase checkpoint and what inhibits it?
Cyclin E-CDK2.
p57, p25, p21.
154
What is the G2/M checkpoint and what inhibits it?
Cyclin B-CDK1.
p57, p25, p21.
155
What is the result of a Cyclin D (t11;14) overexpression?
Multiple Myeloma and Mantle Cell Lymphoma.
156
In what cancer is there a germline mutation of p16?
Familial melanoma.
157
What are the functions of p53?
Arrests cell cycle at G1/S through p21 activation.
Activates DNA repair through GADD45.
Apoptoses through BAX inactivation.
Activation of senescence.
158
How does p53 work?
Normally bound to MDM2, DNA damage/severe hypoxia causes ATM and ATR to phosphorylate p53.
In hyper/neoplasia p14/ARF inactivates MDM2.
159
What is Li-Fraumeni syndrome?
Inherited p53 17p13.1 LoF mutation.
160
What's the effect of mutated p53 on chemo efficiency?
Decreases it.
161
Describe the WNT pathway.
APC is complexed with beta-catenin. In presence of WNT, beta-catenin goes to the nucleus and acts as a TF for proliferation/growth.
162
What is the result of an inherited and spontaneous APC LoF mutation?
Familial Adenomatous Polyposis.
Sporadic Colon Carcinoma. (also hepatoblastoma and hepatocellular carcinoma).
163
What is CDH1 and what do mutations to it cause?
E-cadherin gene (contact inhibition).
Germline LoF mutation causes familial gastric carcinoma.
Spontaneous causes mainly lobular breast carcinoma.
164
Describe VHL and VHL syndrome.
VHL normally complexed with Ubiquitin ligase involved in HIF degradation (inactivated in hypoxia).
LoF of VHL prefents HIF degraation - angiogenesis and cell growth, syndrome is a germline LoF mutation (3p25.3).
Can cause hemangioblastoma in CNS, renal cell carcinoma.
165
Describe the t(14;18) BCL2 translocation.
Translocated to IgH promoter - overexpressed. Apoptosis inhibited - follicular lymphoma.
166
What is HNPCC/Lynch Syndrome the result of?
Defect of mismatch repair. Typically germline MSH2 and MLH1 mutations.
Issue in cecum and ascending colon.
167
What is Xeroderma Pigmentosum?
Defect of nucleotide excision repair.
168
What is ataxia-telangiectasia?
ATM protein kinase mutation - very high risk of lymphoid malignancies.
169
What does a germline BRCA1 and BRCA2 mutation cause?
Familial breastcancer in women, very high risk of ovarian carcinoma.
BRCA2 had that too, breast cancer in men, prostate, pancrease, bile duct, stomach cancer.
170
What is the Warburg effect and how is it identified?
Glycolysis in cancer stops at pyruvate production, in PET scan 'glucose-hungry' neoplastic cells take 18F-fluorodeoxyglycose faster.
171
What are the steps in tumour invasion?
Loss of E-cad and beta catenin, synthesis of MMPs, spread of integrins and other adhesion molecules all over cell surface.
172
Where does cancer almost never metastasize?
Skeletal muscle, spleen and heart extremely rare.
173
What adhesion molecule do solid tumour cells express?
CD44
174
What are the congenital infections?
TORCH - toxoplasmosis, others, rubella, CMV, HSV
175
When do Rubella and Tetracyclins have their worst teratogenic effects?
1st trimester and 2nd/3rd trimester respectively (tooth formation for tetracyclins)
176
What is the APGAR score?
Judges if newborn needs to be resuscitated. Done at 1min and 5min. Normal score 8-10.
Appearance, Pulse, Grimace, Activity, Respiration.
177
When does secure attachment peak?
2-8 months.
178
When does separation anxiety peak?
15 months.
179
What are the main milestones to be reached by 1 month?
Primitive reflexes, Babinski, general muscle tone, response to stimuli, consolability.
180
What are the main milestones to be reached by 2 months?
Head lifting.
Voice-spotting, turning to sound, social smile, following objects past midline.
181
What are the main milestones to be reached by 4 months?
Rolls over.
:ifts head 90 degrees or raises up chest, finds midline, coos, reaches for objects and puts in mouth.
182
What are the main milestones to be reached by 6 months?
Sits up with no head lag.
Raking grasp, transfers objects between hands, babbles, recognizes familiar faces, object permanence.
183
What are the main milestones to be reached by 9 months?
Crawls and pulls to stand.
Points, stranger anxiety, specific babbling.
184
What are the main milestones to be reached by 12 months?
Walks!
Pincers grasp, 1 word phrases, plays patty cake, peekaboo.
185
What are the Piaget cognitive development stages?
Sensorimotor (0-2)
Pre-operational (3-6)
Concrete Operational (7-11)
Formal Operational (12-18)
186
What drugs affect what stage of PG synthesis?
1 - Fosfomycin (enolpyruvate transferase)
2 - Cycloserine (dipeptide synthesis)
3 - Vancomycin (transglycosylase)
4 - beta lactam (transpeptidases)
187
What is MIC and MBC?
Minimum inhibitory and bactericidal concentration.
188
Where is the highest activity of the antifolate drugs?
Trimethoprim (bacteria), Pyrimethamine (protozoa), Methotrexate (human liver)
189
What saturation of CO-Hb leads to unconsciousness and death?
60-70%
190
What part of the brain can hemorrhage as a result of CO poisoning?
Globus pallidus.
191
Describe the Diptheria (Corynebacterium diptheriae) vaccine.
Toxoid.
192
Describe the Tetanus (Clostridium tetani) vaccine.
Toxoid.
193
Describe the Haemophilius influenzae type B vaccine.
Capsule polysaccharide protein conjugate.
194
Describe the Neisseria meningitidis vaccine.
2 - a capsule polysaccharide protei nconjugate and recombinant proteins NadA, NHBA, fHbp.
Should be given to high risk people, travellers to endemic areas, children.
195
Describe the Strep pneumoniae vaccine.
2 - capsule polysaccharide and capsule polysaccharide protein conjugate.
196
Describe the Bordetella pertussis vaccine/
Acellular.
197
Describe the polio vaccine.
2 - inactivated (trivalent, Salk vaccine) and Live (oral, Sabin vaccine).
198
What kind of vaccine are MR and VZV?
Attenuated.
199
What kind of vaccine is the rotavirus vaccine? Who is it given to?
Human-bovine hybrids attenuated. Given to infants.
200
What kind of vaccine is the influenza vaccine and who is it given to?
Inactivated vaccine given to children, elderly, adults (esp. medical personnel).
Attenuated (nasal spray) given to adults 2-50 years old.
201
What kind of vaccine is the HepA vaccine?
Inactivated.
202
What kind of vaccine is the HepB vaccine?
Subunit.
203
What kind of vaccine is the Yellow Fever vaccine?
Attenuated.
204
What kind of vaccine is the Rabies vaccine?
Inactivated.
205
Which phagocytic receptor recognizes DNA viruses?
TLR-9
206
Which phagocytic receptor recognizes LPS?
TLR-4
207
Which antibody type is involved in ADCC?
IgG
