Behavioral science, Psychiatry, Immunology, Pathology, Pharmacology Flashcards
What two groups are compared in a case-control study? What math is used to evaluate findings?
Group with a disease to a group without a disease. Odds ratio (prior exposure or risk factor)
What is the focus of a cohort study? What math is used to evaluate findings?
Exposure or risk (prospective or retrospective). Relative risk
Describe phase 1-4 of a clinical trial
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?)
How do PPV and NPV change with disease prevalence?
PPV increases with increasing prevalence, NPV decreases with increasing prevalence
When are prevalence and incidence the same? When is prevalence> incidence?
Prevalence and incidence are about equal in short duration disease but prevalence is greater in chronic disease
Difference in Relative risk and attributible risk?
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
What is the equation for NNT? NNH?
NNT= 1/ARR NNH= 1/AR
Another word for accuracy? Precision?
Accuracy= validity Precision= reliability
How does an increase in precision effect the statistical power and standard deviation.
Decreases standard deviation, increases statistical power (less likely to miss a positive result)
What is Berkson bias? What type of bias is it?
Berkson bias is selection bias where the study population selected from the hospital is less healthy than the general population
What type of bias do crossover studies help to eliminate? Matching?
Both help eliminate confounding bias
What is the relation between standard deviation and standard error of the mean?
Standard error of the mean is the STDev divided by the square root of the sample size
In positive skew, where is the longer tail? Which measure is the greatest between mean, median and mode?
Longer tail is to the right and the mean is the most affected and thus greatest value
Type I vs Type II errors? What is power?
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
What does the preset p-value usually represent?
Used to judge significance against preset alpha error value (usually 0.05)
How is power affected by increase in sample size?
Power is increased (thus Beta error is decreased)
When does the 95% CI including 0 mean something isn’t statistically significant? What about 1?
0: when mean difference is being compared
1: when odds ratio or relative risk is being compared
What is the Z score for 95% CI? 99%?
95%= 1.96 99%= 2.58 CI = mean +/- Z*SEM
How can you use the CIs of two different groups to see if a significant difference exists?
Usually, if they do not overlap the difference is significant
Four main components of informed consent.
Disclosure, understanding, capacity and voluntariness
What if a minor comes in to the ER and needs immediate blood but the parent religious/cultural beliefs are against it?
If it is emergent, give it anyway
Who typically comes first in the surrogate decision maker pathway between parents or adult children?
Adult children
What is the Tarasoff decision?
Physician is required to directly inform and protect potential victim from harm
When can an infant stand? Walk? Pincer grasp?
Stand and pincer grasp at 10 months, walk by 12-18
When does object permanence arise? Saying mama and dada?
Permanence- 9 months
Mama/Dada- 10 months
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
How many words by age 2? Length of sentences?
200 words, 2-word sentences
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)
Parallel play? Cooperative play?
Parallel by 24-36 months
Cooperative by 4 years
Words by 3 years? Telling stories?
3 years= 1000 words (3 zeros)
Stories by 4 years
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
What type of disease prevention is screening?
Secondary
Who besides old people gets medicare?
Certain disabilities and end stage renal disease
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
What analysis uses a fishbone or Ishikawa diagram?
Root cause analysis
What is failure mode and effects analysis?
Forward looking approach applied before process implementation to prevent failure occurance
Which type of conditioning involved voluntary responses? Involuntary?
Voluntary: operant conditioning
Involuntary: classical conditioning
What is extinction in regard to operant and classical conditioning?
Discontinuation of reinforcement eventually eliminates behavior
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
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
Replacing a warded-off idea or feeling by an unconsciously derived emphasis on its opposite
reaction formation
What personality disorder is splitting associated with?
Borderline personality disorder
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
When must ADHD begin? Intelligence effect?
Before age 12, none
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
Antisocial personality disorder before age 18?
Conduct disorder
What is required for tourette disease? Age and sx
Before age 18 with motor AND vocal tics
What disorders is Tourette syndrome associated with?
OCD and ADHD
How does dopamine change in: depression, huntington, schizophrenia, Parkinson
Decreases in depression, Parkinson
Increases in Huntington and Schizophrenia
What NTs decrease in huntington?
ACh and GABA
What is the relative glutamate level in alzheimers? Which NT is low?
High glutamate, low ACh
Order of loss in orientation?
1st- time, 2nd- place, 3rd- person
Confabulations are characteristic of this? Cause?
Korsakoff syndrome. Thiamine deficiency and destruction of mamillary bodies in late Wernicke encephalopathy
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
Define delusions. Hallucinations.
Delusion: False beliefs that persist despite the facts
Hallucination: perception in the absence of external stimulus
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)
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
What must the timeline be to diagnose schizophrenia?
More than 6 months
1-6 months is schizophreniform
Less than 1 is brief psychotic disorder
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
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
Mild disorder fluctuating between hypomanic and mild depressive symptoms. How long must it last?
Cyclothymic disorder (at least 2 years)
Difference in cyclothymia and dysthymia?
Cyclothymia cycles between mild depression and hypomania while dysthymia is only mild depression
What happens to REM sleep in depression?
Decreased REM latency and increased total REM sleep
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)
Are hallucinations of a deceased person common in grief?
Yeah..
Can ECT be used in pregnancy?
Yeah
What drug besides SSRIs is first line fore panic disorder? Other uses? MOA?
venlafaxine- SNRI
PTSD, Social anxiety disorder
What can be used in acute setting for panic attacks?
Benzodiazepines
What can be used for occasional social anxiety disorder?
Beta-blockers or benzos
How long can adjustment disorder last?
Less than 6 months unless stressor is chronic
Is OCD ego-syntonic or dystonic? What is a first line besides SSRI?
Dystonic, clomipramine (TCA)
What is venlafaxine? Another drug in the class?
SNRI, duloxetine
How long before you can diagnose PTSD? What is it called before?
1 month. Acute stress disorder
Is facticious disorder consciously or unconsciously created?
Conscious (e.g. injecting insulin)
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)
What is the difference in illness anxiety disorder and somatic symptom disorder?
No symptoms (or minimal) in illness anxiety disorder
Are people typically aware of personality disorders?
Nope
Name the cluster A personality disorders (3)
Paranoid, Schizoid, Schizotypal
Name the cluster B personality disorders (4)
Antisocial, Borderline, Histrionic, Narcissistic
Name the cluster C personality disorders (3)
Avoidant, OCPD, Dependent
Why does amenorrhea accompant anorexia?
Loss of pulsatile GnRh secretion
What can be a complication of refeeding?
Increased insulin–> hypophosphatemia–> Cardiac complications
Difference in transsexualism and transvestism?
Transexualism is desire to live as opposite sex. Transvestism is paraphilia, not gender dysphoria (wearing clothes of opposite sex)
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
Decreased production of what can cause narcolepsy? Where is it produced?
Hypocretin (orexin) in the lateral hypothalamus
What might you give to a narcolepsy patient during the day? At night?
Day: stimulants (amphetamines, modafinil)
Night: sodium oxybate (GHB)- acts like GABA
What is precontemplation? Contemplation?
Pre- not acknowledging there is a problem
Contemplation: acknowledging the problem but not yet ready or willing to change
What is a sensitive indicator of alcohol use?
GGT (gamma-glutamyltransferase)
Yawning and diarrhea are signs of withdrawal from what?
Opiods
Why is flumazenil rarely used?
May precipitate seizures (like benzo withdrawal)
Nightmares are a common withdrawal symptom of what?
Stimulants (non-specific)
Associate tactile hallucinations with use of what drug?
Cocaine
Violence and nystagmus indicate intoxication with which drug?
Phencyclidine
What is dronabinol used for?
Antiemetic with chemotherapy and appetite stimulant in AIDS
Describe the effects of MDMA.
Ecstasy is another name. It is a stimulant (increased vitals) and hallucinogenic
Do you use naltrexone for detoxification?
No, could precipitate withdrawal (it is a long-acting opiod antagonist)
Triad of confusion, ophthalmoplegia and ataxia?
Wernicke encephalopathy
What is korsakoff syndrome?
Progression of wernicke encephalopathy involving irreversible memory loss, confabulation, personality change
When does delerium tremens set in?
2-4 days after last drink
What drugs are effective for tourette syndrome?
Antipsychotics like fluphenazine and tetrabenazine
Difference in cocaine and methamphetamine MOA?
Cocaine prevents reuptake, amphetamines prevent reuptake and stimulate release of NTs
Treatment options for EPS? (3)
Benztropine, diphenhydramine, benzos
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
Odd effects of clozapine? Risperidone?
Clozapine: agranulocytosis
Risperidone: hyperprolactinemia
MOA and use of buspirone?
GAD, 5-HT 1A agonist
Is buspirone immediately effective?
No, takes 1-2 weeks
How long does it take for antidepressants to have effect?
4-8 weeks
Most common adverse effect of SNRIs?
Increase in blood pressure
Treatment for serotonin syndrome?
Cyproheptadine (5HT-2 antagonist)
How do TCAs cause arrhythmia? Treatment?
They inhibit sodium channels. Treat/prevent with NaHCO3
Name the 4 MAO inhibitors. Which is selective for MAO-B?
Tranylcypromine, phenylzine, Isocarboxazid, Seligiline (MAO-B only)
What does MAO-A break down? MAO-B?
MAO-A: serotonin and NE
MAO-B: Dopamine
How long must you wait after stopping MAO inhibitors before starting sertoneric drugs?
2 weeks (MAO needs to regenerate since MAO inhibitors are irreversible)
Important side effect of buproprion?
Seizures in anorexic/bulemic pts. No sexual SE
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
What is varenicline? MOA?
Nicotinic ACh receptor partial agonist used for smoking cessation.
Where do you find B and T cells in lymph nodes?
B- Cells: cortex/ follicles
T cells: Paracortex (enlarges in viral infection)
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)
What lymph nodes drain the lower rectum to anal canal above pectinate line? Middle vagina? Prostate? Cervix?
Internal iliac
What lymph nodes drain the kidneys? Uterus?
Para-aortic
Where does the thoracic duct drain to?
Junction of left subclavian and internal jugular veins
Where are T and B cells in the spleen?
T cells: Periarteriolar lymphatic sheath (PALS)
B cells: Follicles in white pulp
Where do APCs capture blood borne antigens for recognition by lymphocytes in the spleen?
Marginal zone
What is the effect of splenectomy on lymphocytes and thrombocytes?
Thrombocytosis due to loss of sequestration and removal
Lymphocytosis due to loss of sequestration
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
What parts of the thymus house mature and immature T cells?
Cortex: immature T cells
Medulla: mature T cells
How does innate immunity recognize pathogens?
Toll-like receptors (TLRs) recognize pathogen-associated molecular patterns (PAMPs)
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
Where are antigens loaded onto MHC-I?
RER after delivery via TAP
Name the associated proteins with each MHC class
MHC-I: Beta 2 microglobulin
MHC-II: Invariant chain (cleaved intracellularly in acidified endosome)
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
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
What cytokines induce Th1 cell formation and Th2 formation?
Th1: IL-12
Th2: IL-4
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
What inhibits Th1 and Th2 cells?
Th1: IL-4 and IL-10 (from Th2)
Th2: IFN-gamma (from Th1)
Which cytokine recruits eosinophils?
IL-5
Cell markers of T Reg cells? (4)
CDs 3,4 and 25 + FOXP3
What is the costimulatory signal needed for CD4 T cell activation?
B7 on the APC to CD 28 (7*4=28)
What is the costimulatory signal for B cell activation?
CD40 on B cell with CD40L on T cell
What is idiotype? Which Ab portion determines it?
Specific antigen binding domain. Fab portion
Where does complement bind Ab? Macrophages?
Both in FC region
What enzyme adds random nucleotides to DNA during recombination to generate antibody diversity?
Terminal deoxynucleotidyl transferase TdT)
What generates antibody diversity? Specificity?
Diversity via random VDJ recombination
Specificity via somatic hypermutation, affinity maturation and isotype switching
Most abundant isotype of Ig in serum?
IgG
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)
What type of antigen is LPS from gram (-) bacteria?
Thymus-independent
What acute phase reactant correlates with ESR?
Fibrinogen
Which acute phase reactant can lead to amyloidosis?
Serum amyloid A (thus autoimmune diseases that are inflammatory cause this type of amyloidosis)
Which two acute phase reactants are downregulated in response to inflammation?
Albumin- conserves AAs for positive reactants
tranferrin- internalized by macrophages to sequester iron
What is the function of hepcidin?
Decreases iron absorption via degradation of ferroportin and decreased iron release
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
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
Name two important inhibitors of complement
1) Decay-accelerating factor (DAF= CD55–> PNH)
2) C1 esterase inhibitor (hereditary angioedema)
How does C1 esterase inhibitor cause angioedema?
Unregulated activation of kallikrein–> increased bradykinin (don’t give ACE inhibitors). Bradykinin causes fever, edema and pain
Another name for IL-1? What does it do to endothelium?
Osteoclast-activating factor
Activates endothelium to express adhesion molecules
What mediates septic shock and cachexia?
TNF-alpha
How does IL-2 cause anti-cancer effects?
Cytotoxic activation of NK cells
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
What does TGF-B do? IL-10?
Both attenuate immune response (TGF beta linked with fibrosis too)
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)
What is the role of pyocyanin in P aeruginosa?
It functions to generate ROS to kill competing microbes
What form of glutathione is needed to control ROS? How is it created?
Reduced glutathione which requires NADPH as a donor to reduce it?
What surface proteins on T cells act as co-receptors for HIV?
CCR5, CXCR4
Good marker to look for to ID macrophages? HIV entry in macrophages? Marker for NK?
Macrophages: CD 14, CCR5
NK cells: CD56
How do superantigens work?
Cross link beta region of TCR to MHC class II on APCs which can activate and CD 4+ cell
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
What is T. brucei?
African sleeping sickness
Name 5 cases in which we give preformed antibodies
Tetanus, Botulism, HBV, Varicella, Rabies
What is the CD4 limit for HIV patients getting MMR and varicella vaccines?
Must be above 200
What type of response is mainly produced by inactivated/killed vaccines? Name 4 examples
Humoral
Rabies, Influenza, Polio (salk), hepatitis A
Where do vasoactive amines act at in type I HSR?
Post capillary venules
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
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
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
Fever, hypotension, flank pain, hemoglobinuria and jaundice following a blood tranfusion. What caused it?
Host antibody reaction against foreign antigen on donor RBCs.
What disorder is associated with an autoantibody to antiphospholipase A2 receptor? Anti-DNA topoisomerase I?
Primary membranous nephropathy
Scleroderma
What immunodeficiency might show up in the 20s and 30s or even be acquired then?
Common Variable Immunodeficiency (decreased plasma cells and immunoglobulins)
Decreased Th1 cell response and decreased IFN gamma?
IL-12 receptor deficiency
What is the best method to detect the 22q11 deletion?
FISH
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
Two causes of SCID and their inheritance?
1) IL-2R gamma chain defective (XLR)
2) ADA deficiency (AR)
What gene is implicated in ataxia telangiectasia? Symptoms?
Ataxia, Spider angiomas (telangiectasia), IgA deficiency
Increased AFP, lymphopenia and cerebellar atrophy
Overlying defect in ataxia telangiectasia and fanconi anemia?
Nonhomologous end joining is defective in DNA repair
What is hyper-IgM syndrome most commonly caused by? Inheritance?
Defective CD40L on Th cells (XLR)
If you have to guess inheritance on immunodeficiency?
XLR (exceptions are ADA SCID, Job syndrome, IL-12 deficiency)
Thrombocytopenia, eczema and infections. What is the problem?
T cells cannot reorganize actin cytoskeleton due to WAS mutation (Wiskott-Aldrich)
Inheritance of phagocyte dysfunction disorders?
AR
What is defective in LAD type I?
Defect in LFA-1 integrin (CD18) on phagocytes which impairs migration and chemotaxis
Giant granules in granulocytes and platelets? Mutation?
Chediak-Higashi. Defect in lysosomal trafficcking regulator gene (LYST)
What is the catalase positive organism that isnt in sketchy?
B. cepacia
Deficient granulocytes mostly leads to what type of infection?
Bacterial (also some fungal/parasites)
What causes hyperacute transplant rejection? Acute? Where do they act?
Hyperacute: preformed antibodies (immediate)
Acute: Host T-cell response
Both attack graft vessels
What type of HSR is chronic transplant rejection?
Type II and IV. Both cellular and humoral responses are involved
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
Which immunosuppressant is known to cause gingival hyperplasia and hirsutism? What is something they might all cause?
Cyclosporine, hyperlipidemia
Main side effect to worry over with sirolimus? Other name?
Rapamycin (mTOR inhibitor), Pancytopenia (pan”sir”topenia)
MOA of mycophenolate mofetil? What is it associated with?
INnhibits IMP dehydrogenase (purine synthesis), associated with invasive CMV infection
MOA of daclizumab and basiliximab?
Block IL-2R
Names of: 1) recombinant IL-2
2)G-CSF and GM-CSF
1) Aldesleukin
2) Filgrastim and sargramostim
What do you use IFN-beta for? IFN gamma?
IFN-beta: MS
IFN-gamma: CGD
What is oprelvekin? Use? 2 more like it?
IL-11 used for thrombocytopenia (so are romiplostim and eltrombopag)
What is alemtuzumab? Bevacizumab? Cetuximab?
Alemtuzumab: CD 52 inhibitor (CLL)
Bevacizumab: VEGF
Cetuximab: EGFR
What is eculizumab?
Stops complement protein c5, used in PNH
What is natalizumab?
alpha 4 integrin which is for WBC adhesion (watch for PML reactivation!!)
Does apoptosis require energy? What change do you see in DNA?
Yes, ATP-dependent. DNA laddering- fragments in multiples of 180 bp
What is pyknosis? Karyorrhexis?
Pyknosis: nuclear shrinkage
Karyorrhexis: fragmentation caused by endonucleases
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
What type of apoptosis is utilized in thymic medullary negative selection?
Fas-FasL mediated apoptosis
What happens to apoptotic bodies?
Engulfed by macrophages (have ligands for macrophage cell receptors on them)
What releases the enzymes that cause liquefactive necrosis in brain, abscesses, and pancreatitis?
Brain: Microglia cells release proteolytic enzymes
Abscess: Neutrophils
Pancreas: Pancreatic enzymes
What causes fat necrosis?
Damaged cells release lipase, which breaks down TGs in fat cells
What causes fibrinoid necrosis?
Immune complexes combine with fibrin which causes vessel wall damage
What causes cell swelling in reversible injury?
Decreased activity of Na+/K+ pumps
Is mitochondrial vacuolization a sign of reversible or irreversible injury?
Irreversible
Region in kidney most prone to ischemic damage?
Medullary segment of proximal tuble or TALH
What brain cells are most vulnerable to hypoxic-ischemic injury?
Purkinje cells of cerebellum and pyramidal cells of hippocampus and neocortex
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
Dystrophic calcification.
Ca deposition in abnormal tissues despite usually being normocalemic
What type of pH favors calcium deposition?
Increased
What is defective in LAD type 2?
Deficient sialyl lewis x (margination and rolling stage vs the tight binding stage of type 1)
What mediates rolling?
Vessel: Selectins
WBCs: Sialyl Lewis X and L-selectin
What mediates tight binding?
Vessel: CAMs
WBCs: CD11/18 (integrins- LFA-1)
What mediates diaPEdesis?
PECAM-1 (CD31)
What vitamins are antioxidants?
ACE
What percent of tensile strength is regained with scars? When?
70-80% at 3 months
What does PDGF do? (3)
Vascular remodeling, SMOOTH MUSCLE MIGRATION (important in atherosclerosis) and fibroblast growth for collagen synthesis
What does FGF do?
Stimulates angiogenesis
What kind of receptor does EGF have?
Tyrosine kinase (cetuximab, herceptin)
What tissue mediator causes fibrosis? Is involved in tissue remodeling?
TGF-beta, metalloproteinases
What type of collagen is first put down in wound healing?
Type III
What are gummas a form of?
Granuloma
What thyroid problem has granulomas?
Subacute throiditis (painful/post viral)
What do macrophages secrete to maintain granuloma formation?
TNF-alpha (remember this based on when you cannot give TNF-alpha inhibitors to TB patients)
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
How do most anemias affect ESR? Renal disease?
Increase it
What is the secondary structure of all amyloid proteins?
Beta-pleated linear sheets
What is the amyloid in AL amyloidosis?
Light chains. Plasma cell disorder or with multiple myeloma
What type of amyloid is with dialysis? Heritable? Age related?
Dialysis: Beta2-microglobulin
Heritable: transthyretin gene mutation
Age: Transthyretin (normal) primarily in cardiac ventricles
What is the amyloid in type II DM?
Amylin
Isolated atrial amyloid in aging? Ventricle?
Atrial: ANP
Ventricular (not completely isolated): transthyretin
What is lipofuscin?
Autophagocytosed organellar membranes that are oxidized and polymerized
What type of cells can be considered dysplastic?
Only epithelial cells
Loss of cell size, shape, and orientation.
Dysplasia
What N/C ratio indicates cancer?
Increased
What do you suspect if you see a dish of cells growing on top of each other?
Loss of contact inhibition–> cancer
What allows cancer cells to invade basement membrane? Lose cell to cell contact?
Invade with collagenases and hydrolases (metalloproteinases)
Contact via E-cadherin inactivation
What does sarcoma mean?
Mesenchymal origin
What is a choristoma?
Normal tissue in a foreign location (e.g. Meckels)
What are the top two leading causes of death in the US?
1 is heart disease, #2 is cancer
Multiple seborrheic keratoses suddenly appear on back
Leser-Trelat sign suggesting GI adenocarcinoma or other visceral malignancy
What cancer can cause hypercalcemia via high vitamin D3?
Lymphoma
Name 5 cancers that can secrete Epo and cause polycythemia
Renal cell carcinoma, hepatocellular carcinoma, hemangioblastoma, pheochromocytoma, leiomyoma
What cancer can cause pure red cell aplasia (anemia with low reticulocytes)? Good syndrome (hypogammaglobulinemia)?
Thymoma for both
What cancer is known for nonbacterial thrombotic endocarditis?
Adenocarcinomas, especially pancreatic
Opsoclonus-myoclonus syndrome?
Neuroblastoma, small cell lung cancer
What can cause paraneoplastic cerebellar degeneration? Antibodies?
Small cell lung cancer, gynecologic/breast cancer, hodgkin lymphoma. Anti Hu, Yo, and Tr in purkinje cells
What cancer do you associate with ALK mutation?
Lung adenocarcinoma (also EGFR and KRAS) (oncogenes)
What cancer do you associate with c-KIT mutation?
GIST (oncogene)
L-myc, N-myc, and C-myc
L-myc: lung cancer
N-myc: neuroblastoma
c-myc: burkitt lymphoma
What tumore do you associate CDKN2A with? Tumor suppressor or oncogene?
Melanoma, pancrease (TSG)
If it has a syndrome what is the likely inheritance and is it an oncogene or TSG?
AD and TSG
What do you associate with merlin?
NF2
What does the VHL gene product do?
Inhibits hypoxia inducible factor 1a
What bug is associated with cholangiocarcinoma?
Liver fluke (Clonorchis sinensis)
What types of cancer are associated with alkylating agents? Aromatic amines?
Alkylators: blood cancer (leukemia/lymphoma)
Aromatic amines: transitional cell carcinoma (bladder)
What type of GI cancer does arsenic cause?
Angiosarcoma of the liver
What type of cancer does vinyl chloride cause?
Angiosarcoma of the liver
Name 4 cancers that can have psammoma bodies
1) Papillary thyroid cancer
2) Serous carcinoma of ovary
3) Mesothelioma
4) Meningioma
What is P-glycoprotein?
MDR1. Used to pump out toxins and classically in adrenal cell carcinoma
Name the four carcinomas that spread via blood.
Hepatocellular carcinoma, renal cell carcinoma, choriocarcinoma, follicular carcinoma of the thyroid
What cancers metastasize to bone?
BLT and a Kosher Pickle
Prostate, breast >lung, thyroid, kidney
Are lung mets to bone lytic or blastic? Breast?
Both are mixed
Where will you most likely find bone mets?
Axial skeleton
What process in cells involves gene activation, protein synthesis and production of organelles?
Hypertrophy
What is the major difference in prognosis of endometrial and prostate hyperplasia?
Endometrial can progress to cancer, BPH does not
How does a decrease in cell size occur?
Ubiquitin-proteosome degradation of the cytoskeleton and autophagy of cellular components
How does metaplasia occur?
Reprogramming of stem cells
Which type of metaplasia carries no risk of progression into cancer?
Apocrine metaplasia of the breast
What vitamin deficiency can cause metaplasia?
Vitamin A (specialized epithelium) such as keratomalacia
What is the mechanism of hypoxic injury?
Low oxygen–> low ATP–> injury
Cherry red appearance of skin suggests what type of poisoning? Chocolate colored-blood?
Skin: Carbon monoxide
Blood: methemoglobinemia
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
What causes apoptosis in cell injury?
Low ATP causes Ca2+ to build up in the cell which can activate enzymes such as caspases
Does necrosis cause inflammation?
Yeah
Type of necrosis where the cell shape and organ structure are preserved but the nucleus disappears
Coagulative (coagulation of proteins preserves cells)
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)
What is the mechanism of death that leads to endometrial shedding in the menstrual cycle?
Apoptosis
What enzyme/complex transfers electrons to oxygen and can cause physiological free radical production?
Cytochrome c oxidase (complex IV)
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
Amyloid with episodes of fever and acute serosal inflammation. Heritability?
Familial Mediterranean Fever (AR)
What is the most commonly involved organ in amyloidosis? What is the result?
Kidney- nephrotic syndrome
What is the protein and heart defect in familial amyloid cardiomyopathy?
MUTATED transthyretin leading to restrictive cardiomyopathy
What receptor on macrophages recognizes LOS from Gram (-) bacteria?
CD14
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
What can activate mast cells (3)?
1) Tissue trauma
2) complement proteins c3a and c5a
3) Cross-linking of cell surface IgE by antigen
What complement proteins combine to form the MAC?
c5b, C6-C9
What does factor XII activate besides the coagulation systems?
Complement and the kinin system (HMWK to bradykinin)
What does bradykinin mediate?
Pain, increased vascular permeability and vasodilation
What induces P and E selectin release?
P selectin: Histmaine mediates release from Weibel Palade body
E: selectin: TNF and IL-1
What is CD 18?
Integrin on leukocytes
Is pseudomonas catalase positive?
Yes
Recurrent candida infections but NBT is normal?
Possibly MPO deficiency
What is the major killing enzyme in eosinophils?
Major basic protein
What is the second activation signal for CD8+ T cells?
IL-2 from Th1 cells
What from macrophages induces Th1 differentiation?
IL-12
Can you give live vaccines to a BTK patient?
No way
What is an increased risk with CVID?
Autoimmune disease and lymphoma
What CD is FAS?
CD 95
What leads to autoimmune lymphoproliferative syndrome?
Mutations in Fas apoptosis pathway
Immune dyregulation, polyendocrinopathy, enteropathy, X-linked
IPEX syndrome due to FOXP3 mutations in regulatory T cells
What is CD25?
IL-2R
Most of the damage is SLE is what type of HSR?
Type III (antigen-antibody complexes)
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)
What rash is associated with lupus besides the malar rash?
Discoid rash (esp. on sunlight exposure)
What type of reaction in lupus causes decreases in RBCs and leukocytes?
Type II HSR
What antiphospholipid antibody is responsible for false positive VDRL and RPR syphilis screening tests?
anticardiolipin
What type of HSR mediates sjogren syndrome?
Type IV
What autoimmune disorder is sjogren syndrome often associated with?
RA
What are anti SSa/Ro and anti SSB/La?
Antiribonucleoprotein antibodies
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
Are visceral organs involved early with CREST?
No.. Yes with scleroderma the real thing
Most common cause of death with scleroderma?
Pulmonary hypertension
What is the classic stable tissue?
Liver.. Can regenerate if needed
What type of collagen forms a keloid?
Type III
What removes type III collagen from a scar? What cofactor is needed?
Collagenase (zinc)
What three mineral deficiencies can cause delayed wound healing?
Vitamin C (collagen hydroxylation), copper (lysyl oxidase- collaged cross linking), zinc (collagenase)
What three features generally distinguish neoplasia from hyperplasia and repair?
It is unregulated, irreversible, and monoclonal
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
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
How many divisions must occur in a cancer cell before the earliest clinical symptoms arise?
30
What is a particularly carcinogenic compound in cigarette smoke?
Polycyclic hydrocarbons
What should you associate with CNS lymphoma in AIDS?
EBV
What cancers can ionizing radiation cause?
Papillary carcinoma of the thyroid, AML and CML
What is PDGF activation associated with in the cancer world?
Astrocytoma
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
What is the one cancer syndrome that is associated with an oncogene?
MEN 2A and 2B RET is a neural growth factor receptor
What cancer is associated with CDK4?
Melanoma
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
What do you suspect if you see unilateral retinoblastoma?
Sporadic mutation. Bilateral and osteosarcoma would suggest germline mutation
In which cancer is Bcl2 overexpressed?
Follicular lymphoma
Tumor cells often downregulate expression what to avoid immune surveillance?
MHC-1
Which cancer characteristically involves the peritoneum and causes omental caking?
Ovarian carcinoma
What does vimentin indicate? S-100?
Vimentin: mesenchyme
S-100: NC cells- melanoma, schwannoma, LCH
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)
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
What happens to the apparent volume of distribution with liver and kidney disease?
Decreased protein binding causes an increase Vd
Where do you expect drug if Vd is 3.5 L? 10.5 L? 42 L?
- 5: plasma
- 5: Extracellular fluid
42: all of body water
What causes a low Vd?
Contained in blood due to large/charged molecules and plasma protein binding
How many half lives does it take to reach steady state? 90%?
4-5 to reach steady state; 3.3 to get 90%
Name three drugs with zero order elimnination?
Phenytoin, ethanol, aspirin
What type of urine pH traps weak acids? Weak bases?
Weak acids are trapped by basic environments
Weak bases are trapped by acidic invironments
Are the following acidic or basic:
TCAs, phenobarbital, aspirin, amphetamines, methotrexate
Acids: aspirin, phenobarbital, methotrexate
Bases: amphetamines, TCAs
What is the effect of aging on the two phases of drug metabolism?
Phase one is lost in aging, phase II is increased
What is the therapeutic index? Is high or low good?
LD50/ED50. High is good (LD can be replaced by TD for toxic dose)
Which has long preganglionics, parasympathetics or sympathetics?
Parasympathetics
Name two parts of the SNS innervated by cholinergic fibers rather than NE.
Adrenal medulla and sweat glands
Which muscarinic receptor is on the heart? Enteric nervous system and CNS?
M2 (Gi), M1 (Gq)
Where do you find the two dopamine receptor types? MOA?
D1- relaxes renal vascular smooth muscle (Gs)
D2- CNS (Gi)
What types of G proteins are the two histamine receptors? Vasopressin?
H1, V1- Gq
H2, V2- Gs
What does increasing cAMP do to smooth muscle?
It inhibits MLCK
What are the two vesicular reuptake inhibitors? What do they inhibit?
Reserpine stops NE loading, vesamicol stops ACh loading
What does ephedrine do at the NE terminal?
Promotes release of vesicles like amphetamine
What is the MOA of bretylium and guanethidine?
Both prevent noradrenergic vesicle release (like botulism to ACh terminals)
What is the MOA of metyrosine?
Prevents tyrosine conversion to DOPA
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
What drug activates bowel and bladder smooth muscle?
Bethanechol (direct cholinomimetic)
What should be your go to drug in glaucoma?
Pilocarpine (contracts ciliary muscle and pupillary sphincter)
What is edrophonium?
Anticholinesterase
What are donepezil and galantamine?
Anticholinesterase (alzheimers)
What is the treatment for MG? What AChE-I crosses into CNS?
Pyridostigmine for MG, physostigmine for CNS
What are glycopyrrolate, hyoscyamine and dicyclomine?
Muscarinic antagonists
What eye problem might atropine cause?
Acute angle-closure glaucoma due to mydriasis (particularly in elderly)
What does dobutamine do?
B1>B2 agonist
Describe the order of the receptors dopamine works on?
D1=D2>B>a
What is fenoldopan?
D1 agonist
What is midodrine?
alpha 1 agonist
What is phenyephrine?
alpha 1> alpha 2 agonist
What is the change in heart rate with NE? Epi?
NE: reflex bradycardia (low B2 activity), Epi has tachycardia
What happens to CO with NE? Epi?
No change with NE (Beta 1 and alpha 1 basically even out), Increases with epi
What is guanfacine? Another drug like it?
Alpha 2 agonist, like clonidine and alpha methyldopa
How do you treat patients on MAO inhibitor who eat tyramine?
Phentolamine
Drug that ends in -osin?
Alpha one inhibitor
Name an alpha 2 inhibitor
Mirtazapine
What change in MAP does epinephrine cause? After alpha blockade?
Increase, decrease (unopposed B2)
What is the effect of sympathetic activity on renin secretion? How?
Increases it via B1 receptors on JGA. Therefore decreased by beta blockers…
What is the effect of alpha agonists and beta agonists on aqueous humor?
Alpha agonist decrease production, beta blockers decrease production
What beta blocker is specifically known to cause dyslipidemia?
Metoprolol
What is the MOA of pufferfish toxin?
Binds Na+ channels in cardiac/nerve tissue and prevents depolarization (e.g. lidocaine)
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.
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
Smells like garlic on the breath poison? Treatment?
Arsenic, Dimercaprol or succimer
What poisoning smelly like burnt almonds? Treatment?
Cyanide. Nitrite + thiosulfate, hydroxycobalamin
Treatment for copper poisoning?
Penicillamine or trientine
Treatment for methanol or ethylene glycol poisoning?
Fomepizole> ethanol (fomepizole inhibits alcohol dehydrogenase)
TCA cardiac effects?
NaHCO3
What antibiotic can cause jaundice and acute cholestatic hepatitis?
Erythromycin
What three drugs can cause gingival hyperplasia?
CCBs, phenytoin, cyclosporine
What is the effect of acute alcohol abuse on P450? Chronic?
Acute: inhibitor
Chronic: Inducer
What is the effect of St. John’s wort on p450?
Inducer
