Things I struggle with Flashcards
case control study
copmapre a group of people with the disease to a group without the disease to look for risk factor. Odds ratio
cohort study
takes a group of people with a risk or exposure to a group without an exposure to see if it increases frequency of disease. Use relative risk
Phase 1 clinical trial
is it safe
phase 2 clinical trial
does it work
phase 3 clinical trial
is it better
phase 4 clinical trial
long term issues
sensitivity
a/a+c proportion of people with disease that test positive for disease. In other words, if the disease is present, the test will be positive. It is good for ruling out disease and indicates low false native. It is good for screening low prevalence disease
specificity
d/D+B- proportion of all people without disease who test negative. Disease is not present if the test is negative. It is good for confirming a positive screening test. It is used to rule in a disease
PPV
probation of positive test results that are true positive. If person tests +then they have disease. Prevalence increases the value
NPV
If person tests negative then they don’t have the disease. High prevalence means the NPV decreases.
incidence
number of new cases/ people at risk
prevalence
number of cases/people in population
chronic disease- changes in incidence and prevalence
prevalence is greater than incidence because there is a larger number of existing cases
when does the odds ratio equal the risk ratio
if the prevalence is low
precision
consistence and reproducibility of the test
accuracy
trueness of the test measurements
reliability
precision
validity
accuracy
Beckson Bias
hospital patients are used instead of normal healthy control
recall bias
can remember more exposures if there is a disease present
Pygmalian effect
observer believes the treatment works so records a biased view
Procedure bias
groups are not treated the same
confounding bias
other multiple factors are playing in
Hawthorne effect
people change behavior when being watched
lead time bias
early detection does not mean increased survival time
1 std
68%
2 std
95%
3std
99.7%
for 95% CI what is z
1.96
for 99% CI what is z
2.58
type 1 error
false positive
type 2 error
false negative- can be influenced by number of participants
beneficience
act in best interest of the patient
non-maleficence
do not harm
exceptions for informed consent
emergency, legally incompetent, witholding psychiatric records, waiver
minor can concept for
sex, drugs, and rock n roll
order of surrogates
spouse>adult children>parents>adult siblings>other relatives
does a proxy come first or spouse in decisions
proxy
transference
patient projects feelings about formative or other important figures onto the physician. Psychiatrist is seen as a parent to the patient
countertransference
doctor projects feelings about people onto the patient.
fixation
partially remaining at a childsih level of development- like focussing on video games
idealization
expressing extremely positive thoughts of self and others while ignoring negative thoughts
identification
modeling behavior after another person who is more powerful- abused child becomes abuser
intellectualization
using factors of logic to emotionally distance oneself
isolation of affect
separating feelings from ideas and events
projection
attributing an unacceptable internal impulse to an expernal source- husband thinks wife is cheating because he is cheating
displacement
transferring avoided ideas and feelings to a neutral person- mother yells at child because husband yelled at her
reaction formation
replacing a warded off idea or feeling by an emphasis on the opposite
repression
involuntarily withholding an idea or feeling from conscious awareness
sublimation
replacing unacceptable wish with a course of action that does not conflict with values
suppression-
intentionally holding off worry
Tourettes
before 18 with sudden rapid recurrent stereotypes motor and vocal tics for over 1 year. associated with OCD and ADHD. Can treat with antipsychotics or tetrabenazeine, guanfacine, and clonidine
positive symptoms of schizo
delusions, hallucinations, disorganized speech, disorganized or catatonic behavior,
negative symptoms of schizo
affective flattening, avolition, anhedonia, asociality, alogia
tuboinfundibular pathway
increased prolactin secretion from schizo treatment
nigrostriatal pathway
EPS effects
mesocortical pathway
negative symptoms
mesolimibic pathway
positive symptoms
brief psychotic disorder vs. schizophreniform
brief is 1 month, and schizophreniform is 1-6 months
schizoaffective
two weeks of hallucinations or delusions without a major mood episode plus periods of concurrent major mood episode and schizophrenia
pathologic grief
persistent and causes functional impairment. meets criteria for major depression
adjustment disorder
emotional symptoms or anxiety or depression causing impairment following an identifiable psychosocial stressor and lasting under six months or over 6 months in the proscenia of a chronic stressor
PTSD
exposure to prior trauma, intrusive re-experiencing of the event, avoid stimuli, changes in cognition and mood and persistently increased arousal- lasts over 1 month with significant distress or dysfunction
somatic symptom disorder
variety of body complaints lasting for months to years associated with excessive persistent thoughts and anxiety about symptoms. May co-occur with medical illness
conversion disorder
loss of sensory or motor function often from an acute stressor. Patient is aware of but indifferent toward symptoms.
illness anxiety disorder
excessive preoccupation with acquiring or having a serious illness despite medical evaluation and reassurance; minimal somatic symptoms
what is decreased in narcolepsy
hypocretin/orexin production
precontemplation
not acknowledging there is a problem
contemplation
acknowledging that there is a problem but not be willing yet to make a change
alcohol withdrawal
tremor, autonomic hyperactivity, seizures
opioid withdrawal
sweating, dilated pupils, piloerection, fever, rhinorrhea, yawning, nausea, stomach cramps, diarrhea
barbituate withdrawal
delirum and life threatening cardiac collapse
bezo withdrawal
sleep disturbance, depression, rebound anxiety, seizure
stimulant withdrawal
post use crash, depression, lethargy, increased appetite, sleep disturbance and vivid nightmares
what can you treat cocaine overdose with and what will kill them if you give them
treat with alpha blockers and benzos. If you give a beta blocker, you get increased hypertension because there is uncontrolled alpha stimulation
violence, impulsive, psychomotor agitation, nystagmus, tachycardia, hypertension, analgesia, psychodis, delirium, seizures
PCP- treat with antipsychotic or benzo
perceptual distortion, depersonalization, anxiety, flashbacks, paranoia,
LSD
euophoria, delusions, anxiety, paned, perception of time is slowed, social withdrawal, hallucinations, red eyes,
weed
irritable, anxiety, depression, insomnia, restlessness, and decreased appetite
pot withdrawal
delerium tremens
autonomic hyperactivity, tremors, anxiety, seizures, seen after surgery because cannot be drinking. hallucinations 12-48 hours after last drink
neuroleptic malignant syndrome
rigidity, myoglobinuria, autonimic instability, hypyrexia- treat with dantrolene, or bromocriptine to get the D2 flowing again
what is in the follicle of a LN
B cells maturation and germinal centers
what is in the medulla of a LN
plasma cells
what is in the paracortex of the LN
T cell
what makes the paracortex of the LN hypoplastic
Digeorge
what makes the paracrotex of the LN hyperplastic
viral infections
what happens after a splencectomy and why
decreased IgM, decreased complement activation, decreased C3b opsonization, and increased susceptibility to encapsulated organisms
what cells are seen after a splenectomy
Howell Jolly bodies, target cells, thrombocyotsis from loss of sequestration, lymphocytosis
what is the thymus derived from
third pouch
when the thymus hypoplastic
Digeorge and SCID
when is the thymus hyperplastic
Myasthenia Gravis
adaptive immunity
T and B cells, highly specific and used immunoglobulin. memory cells cause quicker response the second time
innate immunity
neurophils, macrophages, monocytes, complement- rapid and CRP and TLR bind PAMP
MHC I
binds TCR and Cd8, and is on all nucleated cells. It presents cytosolic proteins or antigens to the CD8 cells
MHC II
binds TCR and CD4 cells. These are only on APC cells. It presents exogenous proteins like bacterial proteins to the T helper cells to activate them
what enhances the activity of NK cells
IL2, IL12, IFNalpha, IFN beta
positive selection of T cells
has TCR that can bind the self-MHC- this occurs in the cortex
negative selection of T cells
eliminate TCRs that bind the self antigen on the dendritic cells or thymic medullary cells. This is the elimination of autoimmune cells- occurs in the medulla
Th1 cells activation
It is induce by IFN gamma and IL12 to secrete IFN gamma which activates the macrophages and the cytotoxic T cells. It is inhibited by IL4 and IL10
Th2 cells activation
induced to differentiate by IL4 and they secrete IL4, IL5, IL10, IL13 which recruit eosinophila for parasite defense and promote IgE production by B cells. It is inhibited by IFN gamma
what does hepcidin do
it decreases iron absorption by degrading ferroportin and decreases iron release from macrophages and leads to anemia of chronic disease
what does CRP do
it is an opsonin which fixes complement and facilitates phagocytosis. Measured clinically as a sign of ongoing inflammation
what mediates the classic complement pathway
IgG and IgM
what are the opsonins
C3b and IgG are the two first degree ones which enhance phagocytosis. They coat cells so the Fc ro C3B receptors can grab onto them
what is the function of C1 esterase inhibitors
it prevents complement activation on self cells
C1esterase inhibitor deficiency
causes hereditary angioedmea due to unregulated activation of chalkier and increased bradykinin. ACE inhibitors make it worse. There is facial swelling, laryngeal swelling and GI issues
C3 deficiency
increases risk of severe recurrent pyogenic sinus and respiratory tract infections and increased susceptibility to HN3
C5-C9 deficiency
leads to Neisseria infections repeatedly
DAF deficiency
complement mediated lysis of RBCs and paraoxysmal nocturnal hemoglobinuria
what cytokine causes fever and acute inflammation- activates endothelium to express adhesion molecules and induces chemokine secretion to recruit WBC
IL-1
what cytokine causes fever and stimulates production of acute phase proteins
IL-6
what cytokine is the major chemotactic factor for neutrophils
IL-8
what cytokine induces differentiation of T cells into Th1 cells. Activates NK cells
IL12
what cytokine mediates septic shock, activates endothelium and causes WBC recruitment and vascular leak
TNF alpha
what cytokine stimulates growth of T helper, cytotoxic, and regulatory T cells and NK cells
IL2
what cytokine supports growth and differenctiaon of bone marrow stem cells
IL3
what cytokine is secreted by NK cells and T cells in response to IL12 from macrophages and stimulates macrophages to kill phagocytes pathogens. Inhibits differentiation of TH2 cells
interferon gamma
what cytokine induces differentiation of T cells into TH2 cells. Promotes growth of B cells and enhances class switching to IgE and IgG
IL4
what cytokine promotes growth and differentiation of B cells and enhances IgA and stimulates growth of eosinophiles
IL5
What cytokine attenuates inflammatory response. Decreases expression of MHCII and Th1 cytokines. Inhibits activates macrophages and dendritic cells. Also secreted by regulatory T cells
IL10
what cytokines are secreted by macrophages
IL1, 6, 8, 12, and TNF alpha
what cytokines are secreted by all T cells
IL2 and IL3
what cytokines are secreted from Th1 cells
interferon gamma
what cytokines are secreted from Th2 cells
Il-4, 5, 10
why is sputum blue green
myeloperoxidase
what are the first two steps in the respiratory burst
NAPH oxidase and superoxide dismutase
what does NADPH do
generates the ROS
what does superoxide dismutase do
produces H2O2
what is the deficiency in with chronic granulomatous disease and what are the risks
increased granuloma formation because there are increased infections from catalase positive species which are able to break down the H2O2 from superoxide dismutase. The ROS are not generated because of the lack of NADPH disputes. Increased s aureus and aspergillus
what are interferons
they are glycoproteins secreted by virally infected cells that prime the uninfected cells which help them degrade factors the virus needs for replication
CD3, CD28, B7, CXCR4, CCR5
T cells
CD4 and CD40L
Helper T cells
CD8, CXCR4, CCR5
Cytotoxic T cells
CD19, CD20, CD21, CD40, MHCII B7
B cells
what receptor binds EBV
CD21
CD14, CCR5, MHCII, B7, Fc, C3b
macrophages
CD16 CD56
NK cells
CD34
hematopoetic stem cells
what are the antigen presenting cells
macrophages, B cells, dendritic cells
what kind of immune response do you get from a live attenuated vaccine and which vaccines are live
indue cellular and humoral responses. nasal flu, measles, mumps, polio (sabin), rubella, varicella, yellow fever
what live vaccines can you give to AIDS patients
yellow, MMR, varicella
what kind of response does killed vaccines give and which are killed
induce only a humoral response which may require a booster. Rabies, flue, polio salk, hepatitis A
anaphylactic atopic, IgE crosslinks on mast cells triggering immediate release of vasoactive amines, that react with post capillary venues. Reaction develops rapidly after antigen exposure because of preformed antibody. Delayed reopens follows due to production of arachidonic acid and metabolites
Type 1 HSN
rhinitis, hay fever, eczema, hives, asthma
HSN1
anaphylaxis
HSN1
IgM and IgG mediated that bind to a fixed antigen on a cell and does cellular destruction by opsonization, phagocytosis, complement and Fc medicated inflammation, antibody mediated cellular dysfunction
HSN2
Direct Coombs
detects antibodies that have adhered to patients RBC
indirect coombs
deterects antibodies in the serum that adhere to other RBC
widespread thrombosis of graft vessel with ischemia and necroses- graft must be removed- why did it happen and what kind of rejection is it
pre-existing antibodies react to donor antigen, and activate complement- hyperacute
Proliferation of vascular smooth muscle, parenchymal atrophy, interstitial fbrosis- atheroscleosis
CD4 T cells respond to recipient APC presneintg donor peptides including allogenic MHC. Type I and IV sensitivity- chronic
bronchiolitis obliterans- dyspnea, dry cough, wheezes
chronic
vasculitis of graft vessels with dense interstitial infiltrate. CD8 cells activated against donor MHC HSN4.
acute-
accelerated atheroscelorisis after transplant
chronic
Increased HTN and CA, with fibrosis and internal thickening, mononuclear infiltrate with tubular atrophy and interstitial firbrosis- after transplant
chronic
vanishing bile ducts- transplant
chronic
maculopapular rash, jaundice, diarrhea, heaptosplenomegaly
gradted immunocomputent T cells proliferate in the immunocomprimised host and reject host cells with foreign proteins- type IV HSN- graft vs host- only happens in liver and bone marrow
intrinsic apoptosis
Bcl2 is anti-apoptotic and BAX or BAK is pro-apoptotic. If BCL2 is overexposed then the cells won’t die
extrinsic apoptosis
Fas ligand or TNF alpha. Immune cells with perforin and granzyme
coagulative necrosis
heart- ischmia or infarct in most tissue but the brain
liquefactive necrosis
bacterial abscesses, brain infarcts due to increased fat content. Neurtrophils release lysosomal enzymes that digest the tissue. Microglia test to be first. Early is cellular debris and macrophages and then its cavitation and cavitation
caseous necrosis
TB, systemic fungi- macrophages wall off the infecting microorganism- granular debris- fragmented cells and debris surround. This leads to cottage cheese appearance
Fat necrosis
enzymatic- acute pancreatitis saponification of peripancreatice fat or breast trauma- outilines of dead fat cells without nuceli- appears dark blue of H and E stain
fibrinoid necrosis
immune reaction in the vessels- immune complexes combine with fibrin and vessel wall damage- vessel walls are thick and pink
gangrenous necrosis
distal extremity after chronic ischemia- dry is ischemia and wet has a superfinection
reversible signs of cell injury
cellular and mitochondrial swelling, nuclear chromatin clumping, membrane blebbing,
irreversible cell injury
mitochondrial permeability and vacuolization, nuclear pyknosis- condensation, karyolysis which is fading and plasma membrane damage and lysosomal rupture
areas first hit by ischemia in brain
ACA/MCA/PCA
areas first hit by ischemia in heart
sunendocardium
areas first hit by ischemia in kidney
PCT
areas first hit by ischemia in liver
area around central vein
areas first hit by ischemia in colon
splenic flexure and rectum
red infarct
occur in venous occlusion and in tissues with multiple blood supplies like liver, lung, intestine, testes, reperfusion
what causes re-perfusion injury
the free radical damage
pale infarct
occur in solid organs with a single blood supply like the heart, kidney, and spleen
chromatolysis
neuronal axonal cell injury- there is increased protein synthesis in effort to repair famed axon- round cellular swelling, displacement of nucleus, dispersion of Nissle substance and Wallerian degeneration
dystrophic calcification
ca desposit in abnormal tisseus due to necrosis or injury- tends to be localized. No abnormal calcium level
metastatic calcification
widespread diffuse deposition of CA. Can be high calcium levels. Tend to be in interstitial issues.
chemotaxtic agents for neutrophils
C5a, IL8, LTB4, kalikreinin, platelet activating factor
what provides the strength to a scar
collagen
keloid- why does it happen
PDGF and TGF beta are controlling fibroblast growth and proliferation. TGF beta stimulates CT synthesis and remodelling in the extracellular matrix. TGF beta tends to decrease in maturation place to limit collagenase. Increased TGF beta from this
PDGF
secreted by platelets and macrophages. Induces vascular remodeling and smooth muscle cell migration stimulates fibroblast growth factor for collagen synthesis
proliferative phase of wound- up to 3 weeks
deposition of granulation tissue and type II collagen. Angiogenesis, epithelial cell proliferation, dissolution of clot and wound contraction
remodeling phase of wound healing- 1 week- 6 months
type III collagen replaced by type collagen I and increased tensile strength
what leads to granuloma formation
IFN gamma and activation of TNF alpha from macrophages induces and maintains granuloma formation
exudate
cellular- cloudy, increased protein, increased LDH, and its from lymphatic obstruction, inflammation/infection, malignancy
transudate
hypocellular, decreased protein, decreased LDH, low specific gravity, increased hydrostatic pressure, decreased oncotic pressure
ESR- increased
products of inflammation coat RBCs and cause aggregation. The denser RBC aggregates fall at a faster rate within a pipette tube. Increased with anemia, infections, inflammation, cancer, renal disease, pregancny
decreased ESR
sickle cell, polycythemia, HF, mucrocytosis, hypofibrinogeninemia
amyloidosis
abnormal aggregation of proteins into beta pelted sheets damage and apoptosis. Apple green bipfringence
primary amyloidosis
deposition of proteins from Ig light chains. Can occur as plasma cell disorder or associated with multiple myeloma. It is restrictive cardiomyopathy, renal disease, hematologic, easy bruising, splenomegaly, hepatomegaly, neuropathy
lipofuscin
wear and tear pigment associated with normal aging. Formed by oxidation and polymerization of autophagocytosed organellar membranes. Autopsy of elderly person will reveal deposits in the heart, colon, liver, kidney, eye, and other organs
hypertrophy vs. Hyperplasia
hypertrophy is increased in size of cells. hyperplasia is the increase innumber of cells. Risk of future malignancy
metaplasia
replacement of one cell type by another. Usually due to exposure to an irritant such as gastric acid or cigaretter smoke. Can undergo malignant transformation if its not removed
neoplasia
uncontrolled clonal proliferation of cells can be benign or malignant
dysplasia
disorded non enoplastic ell growth used only with epithelial cells. Mild dysplasia is usually reversible, severe dysplasia can move onto carcinoma
anaplasia
loss of cell polarity, complete disruption of normal architecture, pleomorphic cells, large nucleus to cytoplasm rain, increased mitotic figures, giant multinucleated giant cells
cancer grade
degree of cellular differentiation and mitotic activity-
cancer stage
degree of localization spread based on site and size of spread to lymph nodes
alkylating agents
leukema and lymphoma
aromatic amines
transitional bladder cancer
aresnic
liver, lung, skin
carbon tetrachloride
liver
nitrosamines
stomach cancer
radon
lung cancer
vinyl chloride
liver cancer
Psammoma bodies in what cancers
papillary thyoid cancer, serous papillary cystadenocarcinomal of ovary, meningioma, malignant mesotheliuoma- dystrophic calcification
breast cancer screening
mammogram once every 2 years from 50-75 years
cervical cancer screening
21-65 and once every 3 years
lung cancer screening
CT annually if 30 year pack history
what amino acids are histones rich in and why
lysine and arginine- they are positively charged
what does histone acetylation do to the DNA
it makes it relaxed making the DNA active
difference between nucleoside and nucelotide
nuceloside is a base plus a sugar and a tide is a base plus ribose plus phosphate
what are the amino acids needed for purine synthesis
glycine, aspartate, and glutamine
what are the pureines
a and g
pyrimidines
C, U, T
what is the rate limiting step of pyrimidine synthesis
CPSII
what is the rate limiting step of purine synthesis
PRPP synthetase
what is the nitrogen source for pyrimidine synthesis
glutamine
increased orotic acid, no increase in ammonia, megaloblastic anemia- what is the deficient enzyme- what pathway is this a part of
UMP synthase and pyrimidine synthesis
what med blocks PRPP synthase
azothioprine/6 mercaptopurine
what enzyme degrades 6-MP and what can cause toxicity from this med
it is metabolized by xanthine oxidase and if also take allopurinol it can lead to toxic accumulation of 6mp
what enzyme takes IMP to GMP and what pathway is this in
It is in the purine denovo synthesis pathway and it is IMP dehydrogenase
what medication blocks the conversion of IMP to GMP aka what enzyme does it block and what is the medication used for
It blocks IMP dehydrogenase- mycophenolate and ribavirin prevents the synthesis of purines in B and T cells
what enzyme takes UDP to dUDP and what blocks it and what pathway is it a part of
It is ribonucelotide reductase and it is blocked by hydroxyurea which is used in Sickle cell to increase the production of fetal hemoglobin. It is part of the pyrimidine pathway
what enzyme takes dUMP to dTMP and what blocks it and what pathway is it a part of
it blocks thymidilate synthase. It is 5 flurouracil. It has increased action with leucovorin as compared to methotrexate. It needs folic acid to continue to blockade the production of pyrimidines
what enzyme recycles dihydrofolate to to tetrahydrofolate and what 2 things block this. What pathway is it a part of and what is the drug to rescue this pathway
tetrahydrofolate reductase is blocked by methotrexate and trimethoprim, and pyrimethamine- these are for humans, bacteria, and protozoa respectively. Leucovorin can rescue this pathway by providing an excess of folic acid
what is the point of the purine salvage pathway and what does it produce
it is a way to recycle purines once they are used. It produces uric acid
what enzyme converts hypoxanthine to xanthine and xanthine to uric acid. What medication blocks this transformation
It is xanthine oxidase which is targeted by allopurinol. Allopurinol and febuxostat decrease the production of uric acid which contributes to gout. Also allopurinol can decrease the metabolism of 6mp and azothioprine
what enzyme converts guanine to GMP and hypoxanthine to IMP
HGPRT
Child is aggressive, has increased uric acid, gout, is aggressive, dystonic, and has self-mutilation like lip biting and finger biting- what is the enzyme that is deficient and what pathway is it a part of- what is the treatment
HGPRT deficiency also called Lesch Nyhan syndrome- It cannot recycle purines, so there is an overproduction of uric acid and continuous denovo purine synthesis- It is treated with allopurinol to help decrease the uric acid production, but it can only really treat the gout
what enzyme takes adenosine to inosine
adenosine deaminase
child has failure to thrive, chronic diarrhea, thrush, and constant recurrent infections with opportunistic and any other infections. No thymic shadow, and no germinal centers on the LN and no migration of T cells in the candida skin test- what enzyme is deficient and what pathway is it a part of
adenosine deaminase deficiency causing SCID it is part of the purine salvage pathway
megaloblastic anemia that does not improve with folate or B12
orotic aciduria
unwinds DNA template at replication fork
helicase
prevents strands from re-anealing
single stranded binding proteins
create double or single stranded breaks in DNA helix to add or remove supercoils
DNA topoisomerase
what is another name for DNA topoisomerase II
gyrase
what blocks prokaryotic DNA topoisomerase II and IV and what is it used for
FQ used for antibiotic
what blocks eukaryotic topoisomerase II and what is it used for
etoposide and teniposide- these are used for leukemia and lymphoma
this is prokaryotic only and elongates the leading strand by adding deoxynucleotides to the 3’ end. Elongates the lagging strand until it reaches the end. what kind of proofreading does it have
it is DNA polymerase III and has 3’-5’ proofreading
This is a prokaryotic enzyme only and it degrades RNA primer and replaces it with DNA and what proofreading does it have
it is DNA polymerase I and it has 5’-3’ proofreading
eukaryotic and has primer and starts the synthesis
polymerase alpha
eukaryotic and has the job of repairing the DNA during replication
polymerase beta
eukaryotic and has the job of doing the lagging strand replication
polymerase delta
eukaryotic and has the job of replacing the leading strand
polymerase epsiolon
eukaryotic and has the job of replicating the mitochondrial DNA
polymerase gamma
catalyzes the formation between the Okasaki fragments
DNA ligase
a RNA dependent DNA polymerase that adds DNA to the 3’ end of chromosomes to avoid loss of genetic material with every duplication- only in eukaryotes
it is telomerase
what does transition mutation mean
purine to purine or pyrimidine to pyrimidine
what does transgression mutation mean
purine to pyrimidine or the other way around
what kind of mutation is a substitution of base but still codes for the same aa
silent mutation
what kind of mutation is a nucelotide substitution resulting in changed amino acid
missense mutation- sickle cell disease
what kind of mutation is a nucleotide substitution leading to an early stop codon
nonsense mutation
what kind of mutation is a deletion or inception of a number of nucleotides not divisible by three, resulting in misreading of all of the nucleotides downstream from the error. Protein may be shorter or longer rand can be disrupted or altered function
frameshift mutation
what kind of mutation is a retained intron in the mRNA leading to a protein with impaired function or altered function
it is a splice site mutation which can lead to cancer, dementia, epilepsy, and some types of beta thalassemia
what changes occur with low glucose on the lac operon site
increased adenylate cyclase activity which increases the cAMP generation from ATP and activates the catabolite activator protein and increased transcription
what changes occur with high lactose on the lac operon site
unbinds the repressor protein and increases the transcription
specific endonuclease release oligonucleotides containing damaged bases. DNA poly and ligase fill and reseal this gap. It repatriate bully and distorted lesions-
nucleotide excision repair
what is defective in xeroderma pigmentosum and what causes damage
defective endonuclease repair- removal of dimer and it is in nucleotide excision repair and it mutates in exposure to sunlight
base specificc glycosylase rmovesthe altered base and creates a base site without a purine or pyrimidine. And then it is filled in with beta polymerase
Base excision repair
new synthesized strand is recognized, mismatched nucleotides are removed and the gap is filled and resealed- occurs in G2 phase
Mismatch repair
what is deceptive in Lynch syndome
mismatch repair
brings two ends of DNA fragments together to repair double stranded breaks- not homologous- what is it called when this is defective
non homologous end joining- it is mutated in ataxia telangactase and Faconi anemia
what are the start codons
AUG which his methionine
what are the stop codons
UGA, UAA, UAG
what are the DNA binding motifs
zinc finger, helix loop helix, helix turn helixm and leucine zipper
how do you terminate prokaryotic RNA transcription
Rho factor knocks off RNA polymerase or a GC rich region self binds creating a hairpin loop which knocks off the polymerase
site where RNA polymerase II and multiple other TFs bid to DNA upstream from the gene- AT rich segment with TATA or CAAT and what would a mutation here do
promoter region and it would decrease the level of gene transcription
stretch of DNA that alters the gene expression by binding TFs
enhancer
site where negative regulators bind
silencer
what makes rRNA in eukaryotes
RNA poly I
what makes tRNA in eukaryotes
RNA poly III
what makes mRNA in eukaryotes
RNA poly II
what inhibits RNA polymerase II
amanita phalloides- death cap mushroom which causes severe hepatotoxicity
what drug inhibits RNA polymerase in prokaryotes and eukaryotes
rifampin
what processes occur in the nucleus after transcription
capping of the 5 prime end, polyadenylation of the trial, spline of the introns and this is the mRNA
what do p bodies do
they are processing bodies which are quality control of the mRNA in the cytoplasm
what do spliceosomes do
they move introns with GU at the 5’ end and AG at the 3’ stie mutations lead to inappropriate splicing and impaired function of the protein
what can cancer cells do with altered splicing to avoid apoptosis
they can alternatively splice to that Fas loses its transmembrane domain this means that it cannot be in the membrane, so that it cannot be bound.
what is at the end of the 3’ end of tRNA
it is the CCA end which carries the amino acid
what charges the tRNA
aminoacyl tRNA syntheses scrutinizes the amino acid before it binds to tRHA and it hydrolyzes and it in charge of the accuracy of the tRNA
what order are the RNA sites
APE: A is incoming and P is growing peptide and E is the exit site
what are the numbers of the eukaryotic and prokaryotic RNA
Euk- 40, 60, 80 and Pro are 30,50,70
what happens when Rb is hypophosphorylated
it is active then so it binds E2F to prevent the progression of G1 to S phase
what role does P53 play in the cell cycle
it checks at G1 to S and G2 to M to make sure there is not too much damage. if there is it cannot be used and causes cell to degrade
dyenin goes which way
retrograde
chines goes which way
anterograde
what drugs act on microtubules
mebensazole, griseofulvin, colchicine, vincristen and blastine which stop growth, and paclitaxel whch stabalizes
infertilty, increased ectopic pregnancy, bronchiectasis, recurrent sinusitis, and situs inverses or dextrocardia on the CXR- what is the disorder and why
Kartagener syndrome and it is from defect in dynein arm, so cilia do not move
collagen found in cartilage, vitreous body, and nucleus pulposis
collagen II
collagen in bone, skin, tension, dentin, fascia, and cornea with late wound repair
type I
collagen found in the basement membrane, basal lamina, and lens
Type IV
collagen found in skin, blood vessels, uterus, fetal tissue and granulation tissue
Type III
OI is associated with which collagen
type I collagen
vascular Ehlers Danlos is associated with which type of collagen
Type III
Alport and Goodpasture involve which collage
Type IV
many fractures wit little trauma, blue sclerae, hearing loss and tooth acbomalities- types of it
abnormal collagen I. It is fatal in type II
hyper extensible skin and hyperbole joints. what type of collage in the this kind. what kind of collagen is the vascular kind and what is the defieincy
type V is the normal kind. vessel is III collagen. It can be a deficiency in the lys oxidase which forms the bonds between tropocollagen. or a deficiency in pro collagen with peptidase enzymes
what aa are the elastin rich in
proline, glycine and lysine
Marfan is a defect in what
fibrillin which is the glycoprotein that forms the sheath around the elastin
what are wrinkles from
decreased collagen and elastin production
what causes panacinar emphysema
overactive elastase because there is not enough alpha 1 antitrypsin blocking it
test used to amplify a DNA fragment
PCR
Blot that looks for mutated DNA
southern blot
blot that looks at RNA for the levels of mRNA which is reflective of gene expression
Northern blot
sample protein is separated by get electrophoresis and transferred to a membrane and label is used to bind a relevant protein. Shows that transcription is increased
western blot
identifies DNA binding proteins aka transcriptin factors using labelled probes
southwestern blot
known antibody to test for presence of antigen
direct ELISA
known antigen to test for antibody
indirect ELISA
ohenotype varies among individuals with the same genotype
variable expressivity
one gene contributes to multiple phenotypic effects
pleiotropy
increased severity with earlier onset of disease in succeeding generations
anticipation
mutations in different loci can produce a similar phenotype
locus heterogeneity
different mutations in the same loci produce the same phenotype
allelic heterogeneity
both normal and mutated tDNA resulting in variable expression in mitochronidrally inherited disease
heteroplasmy
only one allele is alive and the other is inactive with one allele inactivated deletion of the active allele disease. Methylation picks one parent to express the gene
imprinting
maternal imprinting and gene from mom is normally silent but paternal gene is deleted or mutated or there is maternal disomy- hyperphaia, obesity, intellectual disability, hypogonadism, and hypotonia
Prader Wili
dads gene is usually silent but maternal is deleted or mutated. Or parental disomy- it has laughter, seizures, ataxia, and severe intelletual disability
Angelman syndrome
bilateral massive enlargement of kidney dues to large cucsts. mutation in PKD1 with berry aneurysms
autosomal dominant PKD
colon covered in ademotous polyps after puberty
familial adenomatous polyposis
inhertited disorder of blood vessels with branching skin lesions, epistaxis, skin sidocoloration, AV malformations, GI bleeding, hematuria
hereditary hemorrhagic telangactasia
spheroid RBC and defect in spectrin and ankyrin. increased MCHC and increased RDW and treated with splenectomy
hereditary spherocytosis
dpression, and progressive dementia, choreiform movements, caudate atrophy- increased dopamine, decreased GABA, increased ACH in the brain- what chromosome and defect
Huntington and chromosome 4
abnormaility which leads to multiple malignancies at a young age- have sarcoma, breast, leukemia, and adrenal gland cancer, osteosarcoma, and brad adenocarcinoma what is mutated
Li Fraumeni- p53
what is the defect in the gene causing talk, long extremities, precuts excavate, hyperbole joints, and long fingers and toes, and cystic medial necrosis of the aorta, and floppy mitral valve with aibluxation of the lens upward
marfan defect in FBN1 and chromosome 15 fibrillin defect
osteomas, lipomas, sebaceous cysts, and colon polyps and cancer
Gardner syndrome
what genetic condition have the increased risk of rhabdomyosarcoma of the heart
Tuberous scleorsis
what disorder is characterized by RCC pro, angiogenic growth factors, and hemangioblastomas- what chromosome and what defect
VHL and its chromosome 3 tumor suppressor
what does dystrophin do and what is the mutation that covers duchenne
link actin to transmembrane proteins- frameshift
what is the mutation for becker that causes it
non-frameshift- truncated but somewhat functional gene
muscle wasting, catarats, testicular atriphy and frontal balding, arrhythmia- what causes it
CTG repeasts in the DMPK gene that causes abnormal expression of myotonin protein kinase-
large testicles, mental retard, long face, large jaw, everted ears, autism, mitral valve prolapse- what gene and inheritance pattern
Fragil X mutation in the FMR1 gene with trinucleotide expansion
what is the translocation that can cause Downs syndrome
14;21
severe intellecutal disability, rocker bottom feet, microagnathia, low set ears, clenched hands, overlapping fingers, congenital heart disease- whats on the quad screen and disease
trisomy 18 and decreased everything
severe intellectual disability, rocker bottom feet, microphthalamia, microcephaly, cleft lip and palate, holoprosenscepahly, polydactyl and congentiac heart disease and cutis aplasia- quad screen and disorder
trisomy 13 and decreased hcg
woman has multiple miscarriages but when she has the a child, it has dismorphic features and lots of organ abnormalities
unbalanced robertsonian translocation
microcephaly, moderate intellecutal disability, high pitched cry, epicentral folds, and cardiac abnormalities- what is it called and why does it happen
cri du chat syndrome- microdeletion on chromosome 5
elf face, disability, hypercalcemia, and well developed verbal skills, friendly and cardiac problems- what is the disorder and genetics
Willimas and micro deletion on chromosome 7
hypocalcemia, T cell deficiencyy, and cardiac defects like tet of fallot and truncus- what is the defect and gene
22q11 and Digeorge syndrome- no 3 and 4th branchial pouches
what are the fat soluble vitamins
A, D, E, K
what vitamins can be produced by enteric bacteria
folate and vitamin K
what is the vitamin profile after gastric bypass
increased K and folate from bacterial overgrowth and decreased B12, A, D, E, iron
deficiency of this causes night blindness, dry scaly skin, corneal degeneration, some immunosuppression
vitamin A
excess from acute toxicity leads to nausea vomitting vertigo, and blurred vision
vitamin A
chronic toxicity leads to apologia, dry skin, arthralgia, and pseudo tumor cerebri
vitamin A
what can vitamin A be used to treat
AML M3 subtype and measles
deficiency of this: ATP depletion, worked by glucose infusion, highly aerobic tissues are hit first.Start to see with alcohol chronically. Confusion, opthmalplegia, personality change, ataxia, confabulation, personality change, an memory loss. damage to medial dorsal nun the thalamus and maxillary bodies. dry beriberi- polyneuritis and symmetrical muscle wasting. wet is high output cardaic failure and edema
thiamine defiency loss of pyruvate dehydrogenase,e alpha ketoglutartate, transkelotase, and branched cain amino acids
what is the first enzyme in alcohol metabolism
alcohol dehydrogenase
what drug blocks the first step of alcohol metabolism and what is the use for it
fomepizole- it is used an the antidote for methanol and ethylene glycol toxicity
what is the second enzyme in the alcohol metabolism pathway
acetaldehyde dehydrogenase
what blocks the second step of alcohol metabolism
disulfiram
why does alcohol causes steatosis
it increases the NAD/NADH ratio so that it is metabolized instead of close and it used the malate shunt instead so that it prevents gluconeogenesis as well
In what organelle has fatty acid oxidation, acetyl coA production, TCA, oxidative phosphorylation, ketogenesis
mitochondria
where in the cell has glycolysis, HMP shunt, and synthesis of steroids, proteins, and carry acids, nucelotides
cytoplasm
autosomal recessive defect in an enzyme leads to increased methylmalonic acid so metabolic acidosis, hypoglycemia from increased basal metabolic rate leads to increased ketones which leads to AGMA. This inhibits the urea cycle which leads to hyperammonia- hypotonic, lethargic, vomitting, respiratory distress- increased urine propionic acid and methylamalonic acid- what enzyme is deficient
methylmalonic acid mutatse
what is the GLUT for hepatocytes and Beta cells of the pancreas
2
what is the GLUT for neurons and placenta
3
what is the GLUT for fructose in the GI tract
5
what is the GLUT for RBC, BBB, and is generally independent
1
what is the GLUT for skeletal muscle and adipose which is insulin dependent
4
what is the first enzyme in the glycolytic pathway
hexokinase and glucokinase
what is the rate limiting enzyme of glycolysis and what regulates it
PFK 1- increased AMP and fructose 2,6
what down regulates the rate limiting step of glycolysis
increased ATP and citrate from the TCA cyle
what enzyme takes phosphoenolpyruvate to pyruvate
pyruvate kinase
what is pryruvate kinase stimulated by
fructose 1,6 bisphosphate
what down regulated pyruvate kinase
ATP and alanine
what is the deficiency if there is hemolytic anemia due to inability to maintain Na-K ATPase
pyruvate kinase deficiency because the RBC can only go through glycolysis to produce ATP
in the well fed state, which enzyme is stimulated in the fructose 6-P pathway
PFK2 is stimulated so that fructose 2,6 bisphos is increased which turns off glycolysis and k creased glycolysis
in the fasting state, which enzyme is stimulated in the fructose 6p pathway
FBPase is stimulated so fructose 2-6 goes to frucuctose 6p and gluconeogenesis
what are the fates of pyruvate
odd chain FA propyl coA, TCA as oxaloactetate, and AA as oxaloacetate