Behavioral science, Psychiatry, Immunology, Pathology, Pharmacology Flashcards
1
Q
What two groups are compared in a case-control study? What math is used to evaluate findings?
A
Group with a disease to a group without a disease. Odds ratio (prior exposure or risk factor)
2
Q
What is the focus of a cohort study? What math is used to evaluate findings?
A
Exposure or risk (prospective or retrospective). Relative risk
3
Q
Describe phase 1-4 of a clinical trial
A
1: Is it safe (small # of healthy volunteers)
2: Does it work (small # of patients with disease)
3: Is it better? (large #, compares to SOC/placebo)
4: Postmarketing surveillance (can it stay?)
4
Q
How do PPV and NPV change with disease prevalence?
A
PPV increases with increasing prevalence, NPV decreases with increasing prevalence
5
Q
When are prevalence and incidence the same? When is prevalence> incidence?
A
Prevalence and incidence are about equal in short duration disease but prevalence is greater in chronic disease
6
Q
Difference in Relative risk and attributible risk?
A
RR is division of risk of developing disease in exposed group divided by risk of disesase in unexposed group. AR is the same variables but with subtraction
7
Q
What is the equation for NNT? NNH?
A
NNT= 1/ARR NNH= 1/AR
8
Q
Another word for accuracy? Precision?
A
Accuracy= validity Precision= reliability
9
Q
How does an increase in precision effect the statistical power and standard deviation.
A
Decreases standard deviation, increases statistical power (less likely to miss a positive result)
10
Q
What is Berkson bias? What type of bias is it?
A
Berkson bias is selection bias where the study population selected from the hospital is less healthy than the general population
11
Q
What type of bias do crossover studies help to eliminate? Matching?
A
Both help eliminate confounding bias
12
Q
What is the relation between standard deviation and standard error of the mean?
A
Standard error of the mean is the STDev divided by the square root of the sample size
13
Q
In positive skew, where is the longer tail? Which measure is the greatest between mean, median and mode?
A
Longer tail is to the right and the mean is the most affected and thus greatest value
14
Q
Type I vs Type II errors? What is power?
A
Type I:(alpha) saying there is a difference when there isn’t
Type II:(beta) saying there is no difference when there is
Power= 1-beta
15
Q
What does the preset p-value usually represent?
A
Used to judge significance against preset alpha error value (usually 0.05)
16
Q
How is power affected by increase in sample size?
A
Power is increased (thus Beta error is decreased)
17
Q
When does the 95% CI including 0 mean something isn’t statistically significant? What about 1?
A
0: when mean difference is being compared
1: when odds ratio or relative risk is being compared
18
Q
What is the Z score for 95% CI? 99%?
A
95%= 1.96 99%= 2.58 CI = mean +/- Z*SEM
19
Q
How can you use the CIs of two different groups to see if a significant difference exists?
A
Usually, if they do not overlap the difference is significant
20
Q
Four main components of informed consent.
A
Disclosure, understanding, capacity and voluntariness
21
Q
What if a minor comes in to the ER and needs immediate blood but the parent religious/cultural beliefs are against it?
A
If it is emergent, give it anyway
22
Q
Who typically comes first in the surrogate decision maker pathway between parents or adult children?
A
Adult children
23
Q
What is the Tarasoff decision?
A
Physician is required to directly inform and protect potential victim from harm
24
Q
When can an infant stand? Walk? Pincer grasp?
A
Stand and pincer grasp at 10 months, walk by 12-18
25
When does object permanence arise? Saying mama and dada?
Permanence- 9 months
| Mama/Dada- 10 months
26
How many cubes should a toddler be able to stack? When should they be able to feed itself with fork and spoon?
Number = age (yr) * 3
| Feeds itself with fork and spoon by 20 months
27
How many words by age 2? Length of sentences?
200 words, 2-word sentences
28
When can a kid copy line or circle? Use buttons/zippers?
Copy: 3 years (tricycle too)
| Buttons/zippers: 4 years (hops on one foot too)
29
Parallel play? Cooperative play?
Parallel by 24-36 months
| Cooperative by 4 years
30
Words by 3 years? Telling stories?
3 years= 1000 words (3 zeros)
| Stories by 4 years
31
What happens to REM sleep, Sleep onset latency and early awakenings with age?
REM and slow-wave sleep decrease
| Increased sleep onset latency and early awakenings
32
What type of disease prevention is screening?
Secondary
33
Who besides old people gets medicare?
Certain disabilities and end stage renal disease
34
What part of medicare covers hospital insurance? Drugs? Private companise? Basic medical bills?
A: hospitAl insurAnce
B: medical Bills
C: (parts A+B) delivered by private Company
D: Drugs
35
What analysis uses a fishbone or Ishikawa diagram?
Root cause analysis
36
What is failure mode and effects analysis?
Forward looking approach applied before process implementation to prevent failure occurance
37
Which type of conditioning involved voluntary responses? Involuntary?
Voluntary: operant conditioning
Involuntary: classical conditioning
38
What is extinction in regard to operant and classical conditioning?
Discontinuation of reinforcement eventually eliminates behavior
39
Difference in transference and countertransference?
Transference is the patient projecting feelings about formative or other important persons onto doctor.
Countertransference is the doctor doing it to the patient
40
Partially remaining at a more childish level of development? Completely and involuntarily turning back to earlier modes of dealing with the world?
Fixation (e.g. adults fixating on video games)
| Regression
41
Replacing a warded-off idea or feeling by an unconsciously derived emphasis on its opposite
reaction formation
42
What personality disorder is splitting associated with?
Borderline personality disorder
43
Replacing an unacceptable wish with a course of action that is similar to the wish but does not conflict with ones own value system
Sublimation
44
When must ADHD begin? Intelligence effect?
Before age 12, none
45
Loss of development, loss of verbal abilities, ataxia and intellectual disability in girl around age 1-4. Genetics? Common finding?
Rett syndrome: X-linked dominant
| Characteristic hand wringing
46
Antisocial personality disorder before age 18?
Conduct disorder
47
What is required for tourette disease? Age and sx
Before age 18 with motor AND vocal tics
48
What disorders is Tourette syndrome associated with?
OCD and ADHD
49
How does dopamine change in: depression, huntington, schizophrenia, Parkinson
Decreases in depression, Parkinson
| Increases in Huntington and Schizophrenia
50
What NTs decrease in huntington?
ACh and GABA
51
What is the relative glutamate level in alzheimers? Which NT is low?
High glutamate, low ACh
52
Order of loss in orientation?
1st- time, 2nd- place, 3rd- person
53
Confabulations are characteristic of this? Cause?
Korsakoff syndrome. Thiamine deficiency and destruction of mamillary bodies in late Wernicke encephalopathy
54
Main identifier for delirium? Is it permanent?
Changes in level of consciousness with acute onset. It is reversible and generally secondary to other illness or hospitalization
55
Define delusions. Hallucinations.
Delusion: False beliefs that persist despite the facts
Hallucination: perception in the absence of external stimulus
56
When do you typically see: visual hallucinations? Auditory hallucinations? Olfactory halucinations? Tactile?
Visual: medical illness> psychiatric illness
Auditory: psychiatric illness> medical
Olfactory: temporal lobe epilepsy (burning rubber)
Tactile: Alcohol withdrawal and stimulant use (Cocaine crawlies)
57
What is the third possible criteria of the main three besides delusions and hallucinations? E.g. what must be present for diagnosis in a patient with no delusions or hallucinations?
Disorganized speech
58
What must the timeline be to diagnose schizophrenia?
More than 6 months
1-6 months is schizophreniform
Less than 1 is brief psychotic disorder
59
How do you diagnose schizoaffective disorder?
Must have hallucinations/delusions for more than two weeks WITHOUT mood episode plus periods of concurrent major mood episode with schizophrenic symptoms
60
What is folie a deux associated with? Defn of disorder?
Delusional disorder which is a fixed, persistent, false belief system lasting LONGER THAN 1 MONTH
61
Mild disorder fluctuating between hypomanic and mild depressive symptoms. How long must it last?
Cyclothymic disorder (at least 2 years)
62
Difference in cyclothymia and dysthymia?
Cyclothymia cycles between mild depression and hypomania while dysthymia is only mild depression
63
What happens to REM sleep in depression?
Decreased REM latency and increased total REM sleep
64
Name three symptoms that suggest atypical depression
1) Leaden paralysis
2) Hypersomnia or hyperphagia
3) Mood reactivity (can have brief positive mood change in response to positive events)
65
Are hallucinations of a deceased person common in grief?
Yeah..
66
Can ECT be used in pregnancy?
Yeah
67
What drug besides SSRIs is first line fore panic disorder? Other uses? MOA?
venlafaxine- SNRI
| PTSD, Social anxiety disorder
68
What can be used in acute setting for panic attacks?
Benzodiazepines
69
What can be used for occasional social anxiety disorder?
Beta-blockers or benzos
70
How long can adjustment disorder last?
Less than 6 months unless stressor is chronic
71
Is OCD ego-syntonic or dystonic? What is a first line besides SSRI?
Dystonic, clomipramine (TCA)
72
What is venlafaxine? Another drug in the class?
SNRI, duloxetine
73
How long before you can diagnose PTSD? What is it called before?
1 month. Acute stress disorder
74
Is facticious disorder consciously or unconsciously created?
Conscious (e.g. injecting insulin)
75
Difference in somatic symptom disorder and conversion disorder?
Both are unconsciously driven but conversion disorder involves a neurological symptom following an acute stressor. Patients also often don't care about it (la belle indifference)
76
What is the difference in illness anxiety disorder and somatic symptom disorder?
No symptoms (or minimal) in illness anxiety disorder
77
Are people typically aware of personality disorders?
Nope
78
Name the cluster A personality disorders (3)
Paranoid, Schizoid, Schizotypal
79
Name the cluster B personality disorders (4)
Antisocial, Borderline, Histrionic, Narcissistic
80
Name the cluster C personality disorders (3)
Avoidant, OCPD, Dependent
81
Why does amenorrhea accompant anorexia?
Loss of pulsatile GnRh secretion
82
What can be a complication of refeeding?
Increased insulin--> hypophosphatemia--> Cardiac complications
83
Difference in transsexualism and transvestism?
Transexualism is desire to live as opposite sex. Transvestism is paraphilia, not gender dysphoria (wearing clothes of opposite sex)
84
When in the sleep cycle does sleep terror disorder happen? Do they remember it?
Non-REM sleep (slow wave/deep sleep in stage N3). No, they do not remember since it isn't during REM
85
Decreased production of what can cause narcolepsy? Where is it produced?
Hypocretin (orexin) in the lateral hypothalamus
86
What might you give to a narcolepsy patient during the day? At night?
Day: stimulants (amphetamines, modafinil)
Night: sodium oxybate (GHB)- acts like GABA
87
What is precontemplation? Contemplation?
Pre- not acknowledging there is a problem
| Contemplation: acknowledging the problem but not yet ready or willing to change
88
What is a sensitive indicator of alcohol use?
GGT (gamma-glutamyltransferase)
89
Yawning and diarrhea are signs of withdrawal from what?
Opiods
90
Why is flumazenil rarely used?
May precipitate seizures (like benzo withdrawal)
91
Nightmares are a common withdrawal symptom of what?
Stimulants (non-specific)
92
Associate tactile hallucinations with use of what drug?
Cocaine
93
Violence and nystagmus indicate intoxication with which drug?
Phencyclidine
94
What is dronabinol used for?
Antiemetic with chemotherapy and appetite stimulant in AIDS
95
Describe the effects of MDMA.
Ecstasy is another name. It is a stimulant (increased vitals) and hallucinogenic
96
Do you use naltrexone for detoxification?
No, could precipitate withdrawal (it is a long-acting opiod antagonist)
97
Triad of confusion, ophthalmoplegia and ataxia?
Wernicke encephalopathy
98
What is korsakoff syndrome?
Progression of wernicke encephalopathy involving irreversible memory loss, confabulation, personality change
99
When does delerium tremens set in?
2-4 days after last drink
100
What drugs are effective for tourette syndrome?
Antipsychotics like fluphenazine and tetrabenazine
101
Difference in cocaine and methamphetamine MOA?
Cocaine prevents reuptake, amphetamines prevent reuptake and stimulate release of NTs
102
Treatment options for EPS? (3)
Benztropine, diphenhydramine, benzos
103
Do typical or atypical antipsychotics treat postive schizophrenia symptoms? Negative? Which prolongs QT interval?
Typical: Basically only positive
Atypical: positive and negative
Both prolong QT
104
Odd effects of clozapine? Risperidone?
Clozapine: agranulocytosis
Risperidone: hyperprolactinemia
105
MOA and use of buspirone?
GAD, 5-HT 1A agonist
106
Is buspirone immediately effective?
No, takes 1-2 weeks
107
How long does it take for antidepressants to have effect?
4-8 weeks
108
Most common adverse effect of SNRIs?
Increase in blood pressure
109
Treatment for serotonin syndrome?
Cyproheptadine (5HT-2 antagonist)
110
How do TCAs cause arrhythmia? Treatment?
They inhibit sodium channels. Treat/prevent with NaHCO3
111
Name the 4 MAO inhibitors. Which is selective for MAO-B?
Tranylcypromine, phenylzine, Isocarboxazid, Seligiline (MAO-B only)
112
What does MAO-A break down? MAO-B?
MAO-A: serotonin and NE
| MAO-B: Dopamine
113
How long must you wait after stopping MAO inhibitors before starting sertoneric drugs?
2 weeks (MAO needs to regenerate since MAO inhibitors are irreversible)
114
Important side effect of buproprion?
Seizures in anorexic/bulemic pts. No sexual SE
115
How does Mirtazapine work? Who might a specific side effect make it goo for?
alpha 2 antagonist (ant 5HT-2 and 3 antagonist and H1 antagonist. Weight gain makes it desirable for anorexic and some elderly patients
116
What is varenicline? MOA?
Nicotinic ACh receptor partial agonist used for smoking cessation.
117
Where do you find B and T cells in lymph nodes?
B- Cells: cortex/ follicles
| T cells: Paracortex (enlarges in viral infection)
118
What is in the medulla of lymph nodes? Significance?
Medullary cords: closely packed lymphocytes and plasma cells
Medullary sinuses: Communicate with efferent lymphatics and contain reticular cells and macrophages (enlarges with tumor spread to LN)
119
What lymph nodes drain the lower rectum to anal canal above pectinate line? Middle vagina? Prostate? Cervix?
Internal iliac
120
What lymph nodes drain the kidneys? Uterus?
Para-aortic
121
Where does the thoracic duct drain to?
Junction of left subclavian and internal jugular veins
122
Where are T and B cells in the spleen?
T cells: Periarteriolar lymphatic sheath (PALS)
| B cells: Follicles in white pulp
123
Where do APCs capture blood borne antigens for recognition by lymphocytes in the spleen?
Marginal zone
124
What is the effect of splenectomy on lymphocytes and thrombocytes?
Thrombocytosis due to loss of sequestration and removal
| Lymphocytosis due to loss of sequestration
125
What's in the red pulp of the spleen? What cancer can affect it?
RBCs. Hairy cell leukemia causes massive splenomegaly by infiltrating the red pulp
126
What parts of the thymus house mature and immature T cells?
Cortex: immature T cells
Medulla: mature T cells
127
How does innate immunity recognize pathogens?
Toll-like receptors (TLRs) recognize pathogen-associated molecular patterns (PAMPs)
128
Which MHC class is A,B and C which is DP, DQ, DR
MHC-I is types A, B and C. MHC-II is DQ, DP, DR
129
Where are antigens loaded onto MHC-I?
RER after delivery via TAP
130
Name the associated proteins with each MHC class
MHC-I: Beta 2 microglobulin
| MHC-II: Invariant chain (cleaved intracellularly in acidified endosome)
131
HLA subtypes with RA, celiac, Hashimoto, DM, Pernicious anemia, MS.
```
RA: DR4
Celiac: DQ 2 and DQ8
Hashimoto: DR3
DM: DR3, DR4
Pernicious anemia: DR5
MS: DR2
```
132
Which four cytokines enhance NK cell activity? What two mechanisms induce killing by NK cells?
IL-2, IL-12, IFN- alpha and beta
1) Nonspecific activation signal on target cell and/or absence of class 1 MHC on target cell
2) Antibody-dependent cell-mediated when CD16 binds Fc region of bound Ig
133
What cytokines induce Th1 cell formation and Th2 formation?
Th1: IL-12
Th2: IL-4
134
What causes tissue-restricted self-antigens to be expressed in the thymus? Why is this important?
AIRE (autoimmune regulator). This is needed for negative selection meaning that a deficiency results in autoimmune polyendocrine syndrome-1
135
What inhibits Th1 and Th2 cells?
Th1: IL-4 and IL-10 (from Th2)
Th2: IFN-gamma (from Th1)
136
Which cytokine recruits eosinophils?
IL-5
137
Cell markers of T Reg cells? (4)
CDs 3,4 and 25 + FOXP3
138
What is the costimulatory signal needed for CD4 T cell activation?
B7 on the APC to CD 28 (7*4=28)
139
What is the costimulatory signal for B cell activation?
CD40 on B cell with CD40L on T cell
140
What is idiotype? Which Ab portion determines it?
Specific antigen binding domain. Fab portion
141
Where does complement bind Ab? Macrophages?
Both in FC region
142
What enzyme adds random nucleotides to DNA during recombination to generate antibody diversity?
Terminal deoxynucleotidyl transferase TdT)
143
What generates antibody diversity? Specificity?
Diversity via random VDJ recombination
| Specificity via somatic hypermutation, affinity maturation and isotype switching
144
Most abundant isotype of Ig in serum?
IgG
145
What specifically does secretory IgA that prevents mucosal bacteria from being pathogenic? Where does the J chain (secretory component) come from? Function?
Prevents attachment of viruses and bacteria to mucous membranes. From epithelial cells, it protects the Fc portion from luminal proteases (GIT)
146
What type of antigen is LPS from gram (-) bacteria?
Thymus-independent
147
What acute phase reactant correlates with ESR?
Fibrinogen
148
Which acute phase reactant can lead to amyloidosis?
Serum amyloid A (thus autoimmune diseases that are inflammatory cause this type of amyloidosis)
149
Which two acute phase reactants are downregulated in response to inflammation?
Albumin- conserves AAs for positive reactants
| tranferrin- internalized by macrophages to sequester iron
150
What is the function of hepcidin?
Decreases iron absorption via degradation of ferroportin and decreased iron release
151
What activates each pathway of complement: classic, alternative, lectin?
Classic: IgG or IgM
Alternative: microbe surface molecules
Lectin: Mannose or other sugars on microbe surface
152
What are the two primary opsonins in bacterial defense? Which has a second function and what is it?
C3b and IgG. C3b also helps clear immune complexes
153
Name two important inhibitors of complement
1) Decay-accelerating factor (DAF= CD55--> PNH)
| 2) C1 esterase inhibitor (hereditary angioedema)
154
How does C1 esterase inhibitor cause angioedema?
Unregulated activation of kallikrein--> increased bradykinin (don't give ACE inhibitors). Bradykinin causes fever, edema and pain
155
Another name for IL-1? What does it do to endothelium?
Osteoclast-activating factor
| Activates endothelium to express adhesion molecules
156
What mediates septic shock and cachexia?
TNF-alpha
157
How does IL-2 cause anti-cancer effects?
Cytotoxic activation of NK cells
158
What effect does IFN-gamma have on NK cells and on collectively all cells?
NK cell activation
| Increased MHC expression and antigen presentation by all cells
159
What does TGF-B do? IL-10?
Both attenuate immune response (TGF beta linked with fibrosis too)
160
What enzyme is deficient in CGD? What does it do?
NADPH oxidase. It generates reactive oxygen species to eventually be converted to bleach (HCLO radical)
161
What is the role of pyocyanin in P aeruginosa?
It functions to generate ROS to kill competing microbes
162
What form of glutathione is needed to control ROS? How is it created?
Reduced glutathione which requires NADPH as a donor to reduce it?
163
What surface proteins on T cells act as co-receptors for HIV?
CCR5, CXCR4
164
Good marker to look for to ID macrophages? HIV entry in macrophages? Marker for NK?
Macrophages: CD 14, CCR5
| NK cells: CD56
165
How do superantigens work?
Cross link beta region of TCR to MHC class II on APCs which can activate and CD 4+ cell
166
How do endotoxins/LOS (gram - bacteria) work? Are T cells involved?
Directly stimulate macrophages by binding to endotoxin receptor (TLR4/CD14). NO T CELL INVOLVEMENT
167
What is T. brucei?
African sleeping sickness
168
Name 5 cases in which we give preformed antibodies
Tetanus, Botulism, HBV, Varicella, Rabies
169
What is the CD4 limit for HIV patients getting MMR and varicella vaccines?
Must be above 200
170
What type of response is mainly produced by inactivated/killed vaccines? Name 4 examples
Humoral
| Rabies, Influenza, Polio (salk), hepatitis A
171
Where do vasoactive amines act at in type I HSR?
Post capillary venules
172
How long does it typically take for serum sickness to set in? Asked another way, how long does it take to produce antibodies to foreign proteins?
Starts around 5 days after exposure
173
What individuals are particularly at risk for an anaphylactic blood transfusion reaction?
IgA deficient individuals. Anaphylaxis if they get a blood product with any IgA in it
174
What type of HSR is a febrile nonhemolytic transfusion reaction? What bout acute hemolytic transfusion reaction? What is the difference?
Both are type II. Nonhemolytic is against donor HLA antigens and WBCs while hemolytic is against RBCs
175
Fever, hypotension, flank pain, hemoglobinuria and jaundice following a blood tranfusion. What caused it?
Host antibody reaction against foreign antigen on donor RBCs.
176
What disorder is associated with an autoantibody to antiphospholipase A2 receptor? Anti-DNA topoisomerase I?
Primary membranous nephropathy
| Scleroderma
177
What immunodeficiency might show up in the 20s and 30s or even be acquired then?
Common Variable Immunodeficiency (decreased plasma cells and immunoglobulins)
178
Decreased Th1 cell response and decreased IFN gamma?
IL-12 receptor deficiency
179
What is the best method to detect the 22q11 deletion?
FISH
180
What is the cause and presentation of hyper-IgE syndrome? Other name and inheritance pattern?
Job syndrome (AD)
Deficiency of Th17 cells due to STAT3 mutation which causes impaired neutrophil recruitment to infection
Presents with coarse faces, cold abscesses, retained primary teeth, increased IgE and Dermatologic problems
181
Two causes of SCID and their inheritance?
1) IL-2R gamma chain defective (XLR)
| 2) ADA deficiency (AR)
182
What gene is implicated in ataxia telangiectasia? Symptoms?
Ataxia, Spider angiomas (telangiectasia), IgA deficiency
| Increased AFP, lymphopenia and cerebellar atrophy
183
Overlying defect in ataxia telangiectasia and fanconi anemia?
Nonhomologous end joining is defective in DNA repair
184
What is hyper-IgM syndrome most commonly caused by? Inheritance?
Defective CD40L on Th cells (XLR)
185
If you have to guess inheritance on immunodeficiency?
XLR (exceptions are ADA SCID, Job syndrome, IL-12 deficiency)
186
Thrombocytopenia, eczema and infections. What is the problem?
T cells cannot reorganize actin cytoskeleton due to WAS mutation (Wiskott-Aldrich)
187
Inheritance of phagocyte dysfunction disorders?
AR
188
What is defective in LAD type I?
Defect in LFA-1 integrin (CD18) on phagocytes which impairs migration and chemotaxis
189
Giant granules in granulocytes and platelets? Mutation?
Chediak-Higashi. Defect in lysosomal trafficcking regulator gene (LYST)
190
What is the catalase positive organism that isnt in sketchy?
B. cepacia
191
Deficient granulocytes mostly leads to what type of infection?
Bacterial (also some fungal/parasites)
192
What causes hyperacute transplant rejection? Acute? Where do they act?
Hyperacute: preformed antibodies (immediate)
Acute: Host T-cell response
Both attack graft vessels
193
What type of HSR is chronic transplant rejection?
Type II and IV. Both cellular and humoral responses are involved
194
Between cyclosporine, sirolimus and tacrolimus. Which is the outlier? What do they all bind?
Sirolimus prevents IL-2 response while Tacrolimus and Cyclosporine prevent IL-2 transcription
Sirolimus and tacrolimus bind FKBP
Cyclosporine binds cyclophilin
195
Which immunosuppressant is known to cause gingival hyperplasia and hirsutism? What is something they might all cause?
Cyclosporine, hyperlipidemia
196
Main side effect to worry over with sirolimus? Other name?
Rapamycin (mTOR inhibitor), Pancytopenia (pan"sir"topenia)
197
MOA of mycophenolate mofetil? What is it associated with?
INnhibits IMP dehydrogenase (purine synthesis), associated with invasive CMV infection
198
MOA of daclizumab and basiliximab?
Block IL-2R
199
Names of: 1) recombinant IL-2
| 2)G-CSF and GM-CSF
1) Aldesleukin
| 2) Filgrastim and sargramostim
200
What do you use IFN-beta for? IFN gamma?
IFN-beta: MS
| IFN-gamma: CGD
201
What is oprelvekin? Use? 2 more like it?
IL-11 used for thrombocytopenia (so are romiplostim and eltrombopag)
202
What is alemtuzumab? Bevacizumab? Cetuximab?
Alemtuzumab: CD 52 inhibitor (CLL)
Bevacizumab: VEGF
Cetuximab: EGFR
203
What is eculizumab?
Stops complement protein c5, used in PNH
204
What is natalizumab?
alpha 4 integrin which is for WBC adhesion (watch for PML reactivation!!)
205
Does apoptosis require energy? What change do you see in DNA?
Yes, ATP-dependent. DNA laddering- fragments in multiples of 180 bp
206
What is pyknosis? Karyorrhexis?
Pyknosis: nuclear shrinkage
Karyorrhexis: fragmentation caused by endonucleases
207
How does Bcl-2 prevent apoptosis?
It prevents cytochrome C release by binding to and inhibiting APAF-1. APAF-1 normally binds cytochrome c and induces activation of caspase 9
208
What type of apoptosis is utilized in thymic medullary negative selection?
Fas-FasL mediated apoptosis
209
What happens to apoptotic bodies?
Engulfed by macrophages (have ligands for macrophage cell receptors on them)
210
What releases the enzymes that cause liquefactive necrosis in brain, abscesses, and pancreatitis?
Brain: Microglia cells release proteolytic enzymes
Abscess: Neutrophils
Pancreas: Pancreatic enzymes
211
What causes fat necrosis?
Damaged cells release lipase, which breaks down TGs in fat cells
212
What causes fibrinoid necrosis?
Immune complexes combine with fibrin which causes vessel wall damage
213
What causes cell swelling in reversible injury?
Decreased activity of Na+/K+ pumps
214
Is mitochondrial vacuolization a sign of reversible or irreversible injury?
Irreversible
215
Region in kidney most prone to ischemic damage?
Medullary segment of proximal tuble or TALH
216
What brain cells are most vulnerable to hypoxic-ischemic injury?
Purkinje cells of cerebellum and pyramidal cells of hippocampus and neocortex
217
What is the point of a damaged neuron that swells, displaces nucleus to periphery and disperses Nissl substance throughout the cytoplasm?
To increase protein synthesis in effort to repair the damaged axon
218
Dystrophic calcification.
Ca deposition in abnormal tissues despite usually being normocalemic
219
What type of pH favors calcium deposition?
Increased
220
What is defective in LAD type 2?
Deficient sialyl lewis x (margination and rolling stage vs the tight binding stage of type 1)
221
What mediates rolling?
Vessel: Selectins
WBCs: Sialyl Lewis X and L-selectin
222
What mediates tight binding?
Vessel: CAMs
WBCs: CD11/18 (integrins- LFA-1)
223
What mediates diaPEdesis?
PECAM-1 (CD31)
224
What vitamins are antioxidants?
ACE
225
What percent of tensile strength is regained with scars? When?
70-80% at 3 months
226
What does PDGF do? (3)
Vascular remodeling, SMOOTH MUSCLE MIGRATION (important in atherosclerosis) and fibroblast growth for collagen synthesis
227
What does FGF do?
Stimulates angiogenesis
228
What kind of receptor does EGF have?
Tyrosine kinase (cetuximab, herceptin)
229
What tissue mediator causes fibrosis? Is involved in tissue remodeling?
TGF-beta, metalloproteinases
230
What type of collagen is first put down in wound healing?
Type III
231
What are gummas a form of?
Granuloma
232
What thyroid problem has granulomas?
Subacute throiditis (painful/post viral)
233
What do macrophages secrete to maintain granuloma formation?
TNF-alpha (remember this based on when you cannot give TNF-alpha inhibitors to TB patients)
234
Name two blood problems that can cause a decrease in ESR. What does ESR measure?
Indirectly inflammation because inflammation products like fibrinogen coat RBCs and cause aggregation. Denser RBC aggregates fall at a faster rate. Sickle cell and polycythemia can decrease it. Sickle cell has an altered RBC shape and polycythemia has too many RBCs such that the aggregation factors are diluted
235
How do most anemias affect ESR? Renal disease?
Increase it
236
What is the secondary structure of all amyloid proteins?
Beta-pleated linear sheets
237
What is the amyloid in AL amyloidosis?
Light chains. Plasma cell disorder or with multiple myeloma
238
What type of amyloid is with dialysis? Heritable? Age related?
Dialysis: Beta2-microglobulin
Heritable: transthyretin gene mutation
Age: Transthyretin (normal) primarily in cardiac ventricles
239
What is the amyloid in type II DM?
Amylin
240
Isolated atrial amyloid in aging? Ventricle?
Atrial: ANP
| Ventricular (not completely isolated): transthyretin
241
What is lipofuscin?
Autophagocytosed organellar membranes that are oxidized and polymerized
242
What type of cells can be considered dysplastic?
Only epithelial cells
243
Loss of cell size, shape, and orientation.
Dysplasia
244
What N/C ratio indicates cancer?
Increased
245
What do you suspect if you see a dish of cells growing on top of each other?
Loss of contact inhibition--> cancer
246
What allows cancer cells to invade basement membrane? Lose cell to cell contact?
Invade with collagenases and hydrolases (metalloproteinases)
Contact via E-cadherin inactivation
247
What does sarcoma mean?
Mesenchymal origin
248
What is a choristoma?
Normal tissue in a foreign location (e.g. Meckels)
249
What are the top two leading causes of death in the US?
#1 is heart disease, #2 is cancer
250
Multiple seborrheic keratoses suddenly appear on back
Leser-Trelat sign suggesting GI adenocarcinoma or other visceral malignancy
251
What cancer can cause hypercalcemia via high vitamin D3?
Lymphoma
252
Name 5 cancers that can secrete Epo and cause polycythemia
Renal cell carcinoma, hepatocellular carcinoma, hemangioblastoma, pheochromocytoma, leiomyoma
253
What cancer can cause pure red cell aplasia (anemia with low reticulocytes)? Good syndrome (hypogammaglobulinemia)?
Thymoma for both
254
What cancer is known for nonbacterial thrombotic endocarditis?
Adenocarcinomas, especially pancreatic
255
Opsoclonus-myoclonus syndrome?
Neuroblastoma, small cell lung cancer
256
What can cause paraneoplastic cerebellar degeneration? Antibodies?
Small cell lung cancer, gynecologic/breast cancer, hodgkin lymphoma. Anti Hu, Yo, and Tr in purkinje cells
257
What cancer do you associate with ALK mutation?
Lung adenocarcinoma (also EGFR and KRAS) (oncogenes)
258
What cancer do you associate with c-KIT mutation?
GIST (oncogene)
259
L-myc, N-myc, and C-myc
L-myc: lung cancer
N-myc: neuroblastoma
c-myc: burkitt lymphoma
260
What tumore do you associate CDKN2A with? Tumor suppressor or oncogene?
Melanoma, pancrease (TSG)
261
If it has a syndrome what is the likely inheritance and is it an oncogene or TSG?
AD and TSG
262
What do you associate with merlin?
NF2
263
What does the VHL gene product do?
Inhibits hypoxia inducible factor 1a
264
What bug is associated with cholangiocarcinoma?
Liver fluke (Clonorchis sinensis)
265
What types of cancer are associated with alkylating agents? Aromatic amines?
Alkylators: blood cancer (leukemia/lymphoma)
| Aromatic amines: transitional cell carcinoma (bladder)
266
What type of GI cancer does arsenic cause?
Angiosarcoma of the liver
267
What type of cancer does vinyl chloride cause?
Angiosarcoma of the liver
268
Name 4 cancers that can have psammoma bodies
1) Papillary thyroid cancer
2) Serous carcinoma of ovary
3) Mesothelioma
4) Meningioma
269
What is P-glycoprotein?
MDR1. Used to pump out toxins and classically in adrenal cell carcinoma
270
Name the four carcinomas that spread via blood.
Hepatocellular carcinoma, renal cell carcinoma, choriocarcinoma, follicular carcinoma of the thyroid
271
What cancers metastasize to bone?
BLT and a Kosher Pickle
| Prostate, breast >lung, thyroid, kidney
272
Are lung mets to bone lytic or blastic? Breast?
Both are mixed
273
Where will you most likely find bone mets?
Axial skeleton
274
What process in cells involves gene activation, protein synthesis and production of organelles?
Hypertrophy
275
What is the major difference in prognosis of endometrial and prostate hyperplasia?
Endometrial can progress to cancer, BPH does not
276
How does a decrease in cell size occur?
Ubiquitin-proteosome degradation of the cytoskeleton and autophagy of cellular components
277
How does metaplasia occur?
Reprogramming of stem cells
278
Which type of metaplasia carries no risk of progression into cancer?
Apocrine metaplasia of the breast
279
What vitamin deficiency can cause metaplasia?
Vitamin A (specialized epithelium) such as keratomalacia
280
What is the mechanism of hypoxic injury?
Low oxygen--> low ATP--> injury
281
Cherry red appearance of skin suggests what type of poisoning? Chocolate colored-blood?
Skin: Carbon monoxide
Blood: methemoglobinemia
282
What causes methemoglobinemia (specifically and generally)
Fe2+ is oxidized to Fe3+ which cannot carry O2
Oxidant stress (e.g. nitrates) or in newborns
Treat with methylene blue
283
What causes apoptosis in cell injury?
Low ATP causes Ca2+ to build up in the cell which can activate enzymes such as caspases
284
Does necrosis cause inflammation?
Yeah
285
Type of necrosis where the cell shape and organ structure are preserved but the nucleus disappears
Coagulative (coagulation of proteins preserves cells)
286
What causes the bright pink staining of vessel walls in fibrinoid necrosis? When do you classically see this (2)?
Leaking of proteins (including fibrin) into the wall. In vasculitis and malignant hypertension (pre-eclampsia too)
287
What is the mechanism of death that leads to endometrial shedding in the menstrual cycle?
Apoptosis
288
What enzyme/complex transfers electrons to oxygen and can cause physiological free radical production?
Cytochrome c oxidase (complex IV)
289
What organic solvent classically causes damage? Where? How?
CCl4 is converted to CCl3 free radical by hepatocyte p450 and results in cell swelling, death and eventually fatty change in the liver
290
Amyloid with episodes of fever and acute serosal inflammation. Heritability?
Familial Mediterranean Fever (AR)
291
What is the most commonly involved organ in amyloidosis? What is the result?
Kidney- nephrotic syndrome
292
What is the protein and heart defect in familial amyloid cardiomyopathy?
MUTATED transthyretin leading to restrictive cardiomyopathy
293
What receptor on macrophages recognizes LOS from Gram (-) bacteria?
CD14
294
What is the result of TLR activation on cells of the innate immune system?
Upregulation of NF-KB, a nuclear transcription factor that activates immune response genes leading to production of multiple immune mediators
295
What can activate mast cells (3)?
1) Tissue trauma
2) complement proteins c3a and c5a
3) Cross-linking of cell surface IgE by antigen
296
What complement proteins combine to form the MAC?
c5b, C6-C9
297
What does factor XII activate besides the coagulation systems?
Complement and the kinin system (HMWK to bradykinin)
298
What does bradykinin mediate?
Pain, increased vascular permeability and vasodilation
299
What induces P and E selectin release?
P selectin: Histmaine mediates release from Weibel Palade body
E: selectin: TNF and IL-1
300
What is CD 18?
Integrin on leukocytes
301
Is pseudomonas catalase positive?
Yes
302
Recurrent candida infections but NBT is normal?
Possibly MPO deficiency
303
What is the major killing enzyme in eosinophils?
Major basic protein
304
What is the second activation signal for CD8+ T cells?
IL-2 from Th1 cells
305
What from macrophages induces Th1 differentiation?
IL-12
306
Can you give live vaccines to a BTK patient?
No way
307
What is an increased risk with CVID?
Autoimmune disease and lymphoma
308
What CD is FAS?
CD 95
309
What leads to autoimmune lymphoproliferative syndrome?
Mutations in Fas apoptosis pathway
310
Immune dyregulation, polyendocrinopathy, enteropathy, X-linked
IPEX syndrome due to FOXP3 mutations in regulatory T cells
311
What is CD25?
IL-2R
312
Most of the damage is SLE is what type of HSR?
Type III (antigen-antibody complexes)
313
What is the relationship of complement to SLE?
Deficiency of early complement proteins is associated with SLE (these proteins are essential to clear Ag-Ab complexes)
314
What rash is associated with lupus besides the malar rash?
Discoid rash (esp. on sunlight exposure)
315
What type of reaction in lupus causes decreases in RBCs and leukocytes?
Type II HSR
316
What antiphospholipid antibody is responsible for false positive VDRL and RPR syphilis screening tests?
anticardiolipin
317
What type of HSR mediates sjogren syndrome?
Type IV
318
What autoimmune disorder is sjogren syndrome often associated with?
RA
319
What are anti SSa/Ro and anti SSB/La?
Antiribonucleoprotein antibodies
320
What antibody causes pregnant women to be at higher risk for delivering babies with neonatal lupus and congenital heart block?
SS-a (Ro). Thus you must test pregnant patients with lupus for SS-a
321
Are visceral organs involved early with CREST?
No.. Yes with scleroderma the real thing
322
Most common cause of death with scleroderma?
Pulmonary hypertension
323
What is the classic stable tissue?
Liver.. Can regenerate if needed
324
What type of collagen forms a keloid?
Type III
325
What removes type III collagen from a scar? What cofactor is needed?
Collagenase (zinc)
326
What three mineral deficiencies can cause delayed wound healing?
Vitamin C (collagen hydroxylation), copper (lysyl oxidase- collaged cross linking), zinc (collagenase)
327
What three features generally distinguish neoplasia from hyperplasia and repair?
It is unregulated, irreversible, and monoclonal
328
What is historically used to determine clonality? What else can be used? Correct ratio?
```
G6PD isoforms (1:1- one from each parent of A, B and C)
Ig light chain phenotype (3:1 kappa to lambda)
Big cap, little lamb
```
329
How many isoforms of G6PD are active in a cell at any given time? Androgen receptors?
1.. Despite inheriting two in a female, 1 is randomly inactivated due to lyonization. Males only have one since it is on the X-chromosome
330
How many divisions must occur in a cancer cell before the earliest clinical symptoms arise?
30
331
What is a particularly carcinogenic compound in cigarette smoke?
Polycyclic hydrocarbons
332
What should you associate with CNS lymphoma in AIDS?
EBV
333
What cancers can ionizing radiation cause?
Papillary carcinoma of the thyroid, AML and CML
334
What is PDGF activation associated with in the cancer world?
Astrocytoma
335
What happens to activate Ras? What is the result?
GTP bound ras is activated and sends growth signals to the nucleus. It typically inactivates itself by cleaving GTP to GDP
336
What is the one cancer syndrome that is associated with an oncogene?
MEN 2A and 2B RET is a neural growth factor receptor
337
What cancer is associated with CDK4?
Melanoma
338
What is the normal action of p53: 1)if DNA repair is possible? 2) if DNA repair is not possible?
1) Slow the cell cycle and upregulate DNA repair enzymes
| 2) upregulate BAX which disrupts Bcl2 and causes apoptosis
339
What do you suspect if you see unilateral retinoblastoma?
Sporadic mutation. Bilateral and osteosarcoma would suggest germline mutation
340
In which cancer is Bcl2 overexpressed?
Follicular lymphoma
341
Tumor cells often downregulate expression what to avoid immune surveillance?
MHC-1
342
Which cancer characteristically involves the peritoneum and causes omental caking?
Ovarian carcinoma
343
What does vimentin indicate? S-100?
Vimentin: mesenchyme
| S-100: NC cells- melanoma, schwannoma, LCH
344
Vmax is directly proportional to what? Km is inversely proportional to what?
Vmax is proportional to enzyme concentration
| Km is inversely related to affinity of the enzyme for the substrate (e.g. low Km is high affinity)
345
What is plotted on the line-weaver burk plot? What is the slope?
X-axis is 1/[s], Y-axis is 1/[v]
| Slope is km/vmax
346
What happens to the apparent volume of distribution with liver and kidney disease?
Decreased protein binding causes an increase Vd
347
Where do you expect drug if Vd is 3.5 L? 10.5 L? 42 L?
3. 5: plasma
10. 5: Extracellular fluid
42: all of body water
348
What causes a low Vd?
Contained in blood due to large/charged molecules and plasma protein binding
349
How many half lives does it take to reach steady state? 90%?
4-5 to reach steady state; 3.3 to get 90%
350
Name three drugs with zero order elimnination?
Phenytoin, ethanol, aspirin
351
What type of urine pH traps weak acids? Weak bases?
Weak acids are trapped by basic environments
| Weak bases are trapped by acidic invironments
352
Are the following acidic or basic:
| TCAs, phenobarbital, aspirin, amphetamines, methotrexate
Acids: aspirin, phenobarbital, methotrexate
Bases: amphetamines, TCAs
353
What is the effect of aging on the two phases of drug metabolism?
Phase one is lost in aging, phase II is increased
354
What is the therapeutic index? Is high or low good?
LD50/ED50. High is good (LD can be replaced by TD for toxic dose)
355
Which has long preganglionics, parasympathetics or sympathetics?
Parasympathetics
356
Name two parts of the SNS innervated by cholinergic fibers rather than NE.
Adrenal medulla and sweat glands
357
Which muscarinic receptor is on the heart? Enteric nervous system and CNS?
M2 (Gi), M1 (Gq)
358
Where do you find the two dopamine receptor types? MOA?
D1- relaxes renal vascular smooth muscle (Gs)
| D2- CNS (Gi)
359
What types of G proteins are the two histamine receptors? Vasopressin?
H1, V1- Gq
| H2, V2- Gs
360
What does increasing cAMP do to smooth muscle?
It inhibits MLCK
361
What are the two vesicular reuptake inhibitors? What do they inhibit?
Reserpine stops NE loading, vesamicol stops ACh loading
362
What does ephedrine do at the NE terminal?
Promotes release of vesicles like amphetamine
363
What is the MOA of bretylium and guanethidine?
Both prevent noradrenergic vesicle release (like botulism to ACh terminals)
364
What is the MOA of metyrosine?
Prevents tyrosine conversion to DOPA
365
How do amphetamines causes NE release from terminal?
They use the NE transporter to enter the presynaptic terminal where they use VMAT to enter secretory vesicles. This displaces NE from the vesicles. Once enough NE has been displaced, the action of NET reverses and NE is expelled into the synaptic cleft
366
What drug activates bowel and bladder smooth muscle?
Bethanechol (direct cholinomimetic)
367
What should be your go to drug in glaucoma?
Pilocarpine (contracts ciliary muscle and pupillary sphincter)
368
What is edrophonium?
Anticholinesterase
369
What are donepezil and galantamine?
Anticholinesterase (alzheimers)
370
What is the treatment for MG? What AChE-I crosses into CNS?
Pyridostigmine for MG, physostigmine for CNS
371
What are glycopyrrolate, hyoscyamine and dicyclomine?
Muscarinic antagonists
372
What eye problem might atropine cause?
Acute angle-closure glaucoma due to mydriasis (particularly in elderly)
373
What does dobutamine do?
B1>B2 agonist
374
Describe the order of the receptors dopamine works on?
D1=D2>B>a
375
What is fenoldopan?
D1 agonist
376
What is midodrine?
alpha 1 agonist
377
What is phenyephrine?
alpha 1> alpha 2 agonist
378
What is the change in heart rate with NE? Epi?
NE: reflex bradycardia (low B2 activity), Epi has tachycardia
379
What happens to CO with NE? Epi?
No change with NE (Beta 1 and alpha 1 basically even out), Increases with epi
380
What is guanfacine? Another drug like it?
Alpha 2 agonist, like clonidine and alpha methyldopa
381
How do you treat patients on MAO inhibitor who eat tyramine?
Phentolamine
382
Drug that ends in -osin?
Alpha one inhibitor
383
Name an alpha 2 inhibitor
Mirtazapine
384
What change in MAP does epinephrine cause? After alpha blockade?
Increase, decrease (unopposed B2)
385
What is the effect of sympathetic activity on renin secretion? How?
Increases it via B1 receptors on JGA. Therefore decreased by beta blockers...
386
What is the effect of alpha agonists and beta agonists on aqueous humor?
Alpha agonist decrease production, beta blockers decrease production
387
What beta blocker is specifically known to cause dyslipidemia?
Metoprolol
388
What is the MOA of pufferfish toxin?
Binds Na+ channels in cardiac/nerve tissue and prevents depolarization (e.g. lidocaine)
389
What is the toxin from reef fish? How does it work? What does it look like?
Ciguatoxin, opens Na+ channels and causes depolarization. Mimics cholinergic poisoning.
390
What type of poisoning can you get from spoiled dark meat fish? What does it look like? How?
Histamine (scombroid poisoning) due to bacterial histidine decarboxylase converting histidine to histamine. Mimics anaphylaxis
391
Smells like garlic on the breath poison? Treatment?
Arsenic, Dimercaprol or succimer
392
What poisoning smelly like burnt almonds? Treatment?
Cyanide. Nitrite + thiosulfate, hydroxycobalamin
393
Treatment for copper poisoning?
Penicillamine or trientine
394
Treatment for methanol or ethylene glycol poisoning?
Fomepizole> ethanol (fomepizole inhibits alcohol dehydrogenase)
395
TCA cardiac effects?
NaHCO3
396
What antibiotic can cause jaundice and acute cholestatic hepatitis?
Erythromycin
397
What three drugs can cause gingival hyperplasia?
CCBs, phenytoin, cyclosporine
398
What is the effect of acute alcohol abuse on P450? Chronic?
Acute: inhibitor
Chronic: Inducer
399
What is the effect of St. John's wort on p450?
Inducer
