exam 1 review Flashcards
relevant features of the infant/toddler exam:
delayed growth
development
abuse/neglect
Immunizations
relevant features of the child exam (3-12 years):
visual/hearing deficits
accidents
abuse/neglect
immunizations
relevant features of female youth (3-12 years) exam:
rubella immunization, contraception, STDs, substance abuse
relevant features of the male youth (13-24 years) exam:
MVA, STDs, contraception, substance abuse
relevant features of the adult exam (25-44 years):
Female: CA, BP, substance abuse, eating disorders
Males : MVA, BP, cholesterol, DM, substance abuse, family violence
relevant features of middle aged exams (45-54 years):
Females: osteoporosis, DM; lung, colon, skin, and breast CA
Males: prostate/lung/skin/colon CA, ischemic heart, DM
relevant features of senior citizen exams:
Elder abuse, falls, drug related interactions, nutrition, CA
which vaccine is given to newborns immediately following birth? (AKA first vaccine received)
Hep B
In addition to Hep B, which other vaccines are received starting 1-2 months post-birth?
RV, DTaP, Hib, PCV13, IPV, yearly influenza (starting at 6 months)
key milestone at 6 months:
begins to sit without support
key milestone at 12 months:
says “mama” and “dada”
key milestone at 18 months:
begins to walk around towards the end of 18 months
minors who are allowed to consent to services on their own, without parental consent:
Minor who has graduated from HS
Minor who has been pregnant
Minor who has been married
Minor who has received court’s decree of emancipation
what are some treatments/diagnostic tests that minors can receive without parental consent:
Can provide informed consent for diagnostic tests and treatments related to a “reportable disease”:
Contraception, pregnancy, and STD testing
Health services to treat pregnancy, STDs, and prenatal care, “not including abortions”
Inpatient mental health treatment (voluntary consent, 14+ years)
Outpatient mental health (any minor over 14 years)
Substance abuse treatment
Emergency situations
How do USPSTF grade guidelines?
Grade A through Grade I
Grade A - recommends the service as there is a high certainty that the net benefit is substantial. Suggest to provide the service.
vs.
Grade I - concludes that current evidence is sufficient to asses the balance of benefits and harms, evidence is lacking, is of poor quality, or is conflicting. Balance of benefits and harms cannot be determined. Suggestion is that if the service is offered, patients should know about the uncertainty.
explain basic concepts of XR imaging:
XRays shot towards the patient
There is either absorption, partial absorption, scatter, or penetration
XRs that pass through the patient and penetrate the detector film, create an image
Few pass through - white
Many pass through - black
Differential tissue absorption based on:
Atomic weight (density)
Tissue depth (thickness)
2D representation of 3D structures - superimposition
explain the concept of CT imaging:
XRs used but in narrow slices
Generator and detector rotate completely around the patient
Computer reconstructs data to create a 2D image slice
Scan = series of multiple slices
Cross sectional anatomy
explain the concept of US imaging:
uses sound waves, based on the density of the tissue
explain the concept of MRI imaging:
magnetic and radiographic waves, non-ionizing radiation
explain the concept of nuclear medicine:
injects radioactive substance into the body to visualize function (PHYSIOLOGY), uses ionizing radiation
what does radiopaque/radiodensity mean:
few XRs pass through - appears white - metal
what does radiolucent mean?
many XRs pass through - appears black - air
Categorize different tissues from least to most opaque on x-ray including: air, fat, soft tissue, bone, and metal.
(least opaque) Air - fat - soft tissue (solid organs and fluid) - bone - metal (most opaque)
define hypodense/hypoattenuating:
CT terminology
appears dark
e.g. air
define isodense/isoattentuating:
CT terminology
two structures appear the same
define hyperdense/hyperattenuating:
CT terminology
appears bright
i.e. metal
what imaging modalities use ionizing radiation?
CT, XR, nuclear med
define “screening”:
presumptive identification of previously unrecognized condition
how are screenings conducted?
Conducted via procedures, exams, tests
Preliminary in design
Confirmation of diagnosis required (additional tests, exams, evaluations)
define sensitivity:
Correctly identify as diseased as those who actually have the disease
Sn=1-false negative rate
Sn= (true positive)/(true positive)+(false negative)
SNOUT - high sensitivity to rule out
If it is 100% sensitive, all negatives are true negatives
define specificity:
Correctly identify as non-diseased as those actually without the disease
Sp=1-false positive rate
Specificity=(true negative)/(true negative)+(false positive)
SPIN - high specificity to rule in
If it is 100% specific, positives are true positives
define positive predictive value:
Proportion of true positive of all those testing positive
PPV (+) = (true positive)/(true positive)+(false positive)
define negative predictive value:
Proportion of true negative of all those testing negative
NPV (-) = (true negative)/(true negative)+(false negative)
how does prevalence affect PPV, sensitivity, NPV, and specificity?
As prevalence increases, PPV and sensitivity increase (more common in population, more likely to be a true positive)
As prevalence increases, NPV and specificity decrease (more common in population, less likely to be a true negative)
what is a dietary reference intake (DRI)?
estimates of the amounts of nutrients required to prevent deficiencies and maintain optimal health and growth; expand the recommended daily allowances and establish upper limits on the consumption of some nutrients. Focuses on lifelong health - goes beyond just dietary deficiencies
what is an EAR?
EAR - estimated average requirement
Average daily nutrient requirement estimated to meet the requirement of ½ of the healthy individuals in a particular life stage and gender group
Intakes below the EAR need to be improved because the probability of inadequacy is 50%
what is an RDA?
RDA - recommended dietary allowance
Average daily nutrient intake level sufficient to meet the requirements of NEARLY ALL individuals in a particular life stage and gender group
Intakes between the EAR and RDA likely need improvement because the probability of adequacy is <98%
Intakes at or above the RDA can be considered adequate
what is an adequate intake (AI)?
Set if sufficient scientific evidence is not available to calculate an EAR or RDA
Based on nutrient intake by a group of apparently healthy people
Intakes above AI can be considered adequate
what is the tolerable upper intake level?
Highest average daily nutrient intake level that is likely to pose no risk or adverse health effects to almost all individuals of the general population
Intakes between the UL and RDA can be considered to have no risk for adverse effects
what is an estimated energy requirement (EER)?
amount of food energy (calories) needed to balance energy expenditure to maintain body size, body composition, and a level of necessary and desirable physical activity consistent with long term good health
what is the EER for women?
2100 kcals
what is the EER for men?
2900 kcals
what are the 3 main energy needs in humans?
resting metabolic rate (RMR) - 60%
thermic effect of food - 10%
physical activity - 30%
what are some factors that can affect resting metabolic rate (RMR)?
-growth
-hospitalization during recovery from serious injuries such as infection or burns
-pregnancy
-lactation
what is BMI?
body mass index
used as an index of an ideal body weight
may not be appropriate for muscular individuals
BMI= weight (kg)/height squared (m2)
BMI and body weight ranges for adults:
BMI <18.5: underweight
BMI 18.5 to <25: healthy
BMI 25 to <30: overweight
BMI 30 or higher: obesity
describe MyPlate:
MyPlate: designed by the US Department of Agriculture to graphically illustrate its recommendations as to what food groups and how much of each should be consumed daily
5 food groups: vegetables, grains, protein, fruit, and dairy
number of servings depends on age and sex
cons: does not include fats, people need to have access to the graphic
what were the changes made to the nutrition facts label on July 1, 2021?
Servings/calories noted with larger, bolder type
Added sugars, vitamin D, and potassium are included
Vitamins A and C, total fat, and calories from fat removed
Serving size adjusted to reflect amounts people are now consuming
Updated daily values
Proposed addition/removal of certain micronutrients is based on newer data on the risk for underingestion
summarize the key steps during pre-initiation of eukaryotic DNA replication:
TIME SETTING: in the final phases of mitosis
- ORC (origin replication complex) recognizes eukaryotic origins of replication/identifies epigenetic modifications; works in conjunction with HBO1
- Cdt1 and Cdc6 (origin licensing factors) use ATP to load the replicative helicase complex (MCM) onto the DNA next to the origin
- phosphorylation via DDK –> DDK dependent complex (G1 phase - pre-replicative complex)
- polymerase E added —> helicase activated (CMG complex/pre-initiation complex/S phase)
- polymerase alpha and delta added —> complete replisome/ready for DNA replication
how does the MCM helicase complex “melt” into DNA?
hydrolyzes ATP to hydrolyze DNA
when do the pre-replicative and pre-initiation processes take place?
pre-replicative - G1 phase
pre-initiation - S phase
compare and contrast the pre-replicative and pre-initiation phases?
pre-replicative:
DDK is phosphorylating, allowing other proteins to bind
occurs in G1 phase
pre-initiation:
polymerase E added and activates helicase (CMG complex)
followed by polymerase alpha and delta
complete replisome is formed
occurs in S phase
what is the function of polymerase alpha?
-reads the template strand and synthesizes RNA primer from 5’ to 3’ on the complementary strand
-the primer contains a free 3’ -OH end upon which DNA polymerase can add nucleotide monomers
what is the function of replication protein A?
RPA
prevents re-annealing
in what direction does DNA replication occur?
nucleotides are added in the 5’ to 3’ direction
what is the function of polymerase E?
reads parental strand and synthesizes the complementary strand in a CONTINUOUS fashion
lEading - Epsilon
what is the function of polymerase delta?
reads parental strand and synthesizes the complementary strand in a DISCONTINUOUS fashion
therefore, needs numerous primers and numerous polymerases
Okazaki fragments and DNA ligase
deltA - lAgging
what is proliferating cell nuclear antigen (PCNA)?
fits around DNA primer and template strand
DNA polymerase attaches to it
acts as a progressivity factor and increases speed
what is the function of Fen 1?
flap endonuclease that removes DNA overhang (DNA sequences that overlap with the primer)
what is the function of RNAse H1?
removes RNA primer fragments
what is involved in DNA replication termination?
-destruction of the MCM (CMG) complex
-activity of topoisomerase IIA
-activity of Holiday Junction Resolvase (helps merge the replication bubbles together)
replication forks/bubbles merge as they expand
form larger replicons until the chromosome is replicated
what is the function of topoisomerases?
superhelical tension is created by the helicase, in front of the replication fork
may prevent replication from occuring further
tension relieved by topoisomerases
contrast activities of Type 1A, 1B, and IIA topoisomerases:
1A: single DNA strand is nicked and then the opposite strand is passed through to relieve superhelical tension, happens fast
1B: introduces a single strand nick and the strand is rotated around, happens fast
IIA: introduces a double strand break, using homodimeric enzymes in eukaryotes (the things holding the spaghetti), slower process, USED IN DNA REPLICATION
what is common between all topoisomerase types?
break DNA via a transesterification reaction using an active site tyrosine as a nucleophile to attack the sugar phosphate backbone
explain the “telomere end replication problem”
-eventually, run out of space to put primers at the 3’ end of the lagging strand
-some DNA will be lost
-cells undergoing rapid synthesis/growth will lose DNA especially
-overall loss of telomere length
what is the telomere repeat?
(TTAGGG)n
what is the result of the telomere end replication problem?
loss of telomere sequences leads to cell senescence
AKA permanent shit down of the cell cycle within a cell
prevents CA (turning off replication)
**cell senescence is linked to premature aging - secretes factors that cause stem cells to age prematurely
what is the function of telomerase?
replicates single stranded telomere DNA
what are the 2 main subunits of telomerase?
nucleoprotein complex of multiple protein subunits combined with an RNA molecule.
TERT: RNA dependent DNA polymerase
TERC: RNA molecule that serves as a template to synthesize the telomeric sequence repeats
“teRt Reads”
when is telomerase known to be activated during?
embryogenesis (fetal tissue) and in stem cells
research says during other times too
describe the telomerase process:
- telomerase binds to the 3’ end of the telomere sequence, along with an RNA template
- telomerase catalyzes the addition of bases, restoring the telomere length
- DNA polymerase extends and seals the DNA strands
effects of genotoxic agents:
XRs, oxygen radicals, alkylating agents, spontaneous reactions
UV light, polycyclic aromatic hydrocarbons
Replication errors
etc.
what are the cellular consequences of exposure to genotoxic agents?
-transient cell cycle arrest
-inhibition of transcription, replication, and chromosome segregation
-apoptosis
-senescence (cell cycle arrest)
-mutations or chromosome aberrations (cancer, aging, inborn disease)
what is genomic instability?
-a process by which the cell accumulates mutations or chromosome damage
-DNA repair mechanisms may not be able to cope with or recognize the changes
may lead to:
-replication fork stalling
-loss of polymerase proofreading ability
-defects in DNA repair mechanisms
-translesion DNA synthesis over DNA damage
-reduced dNTPs selectivity
how does DNA polymerase proofreading work?
-3’ to 5’ exonucleotide ability
-removes incorrect bases
-polymerase “chews back” and fixes the 3’ end incorrect base
describe the Mismatch Repair (MMR) system:
- recognition by Msh2 and Msh6
- recruitment of endonuclease (Mlh1, Pms2) complex
- Exo1 exonuclease removes the mismatched base
- DNA synthesis (polymerase E or D) and ligation (DNA ligase)
what is Lynch Syndrome? What causes it?
genetic disorder characterized by early onset non-polyposis colorectal CA
caused by inherited mutations that effect Mismatch Repair System (MMR)
what are microsatellite DNA?
regions of small repetitive DNA stretches (2-6 bases)
tandemly repeated multiple times
also known as “short tandem repeats” (STR)
due to their repetitive structure, they are prone to strand misalignment during DNA replication - INDELS (insertions and deletions)
which repair system recognizes INDELS?
Mismatch Repair (MMR)
prevents micro-satellite instability that leads to triplet expansion genetic disorders: Fragile X and Huntington’s Chorea
compare and contrast DNA proofreading with MMR:
DNA proofreading can chew back on one base at a time, whereas MMR can recognize micro-satellite regions and correct INDELS (numerous base pairs)
both utilize exonuclease activity
DNA proofreading doesn’t use endonucleases? (DNA polymerase is what chews back on it)
explain how the NER pathway is multirole:
can remove both UV induced DNA damage (cyclobutane pyrimidine dimers, CPD) and bulky adducts cross linked to DNA
what is the nucleotide excision repair (NER) pathway:
- recognition (Centrin2)
- recruitment of TFIIH complex - a basal transcription factor)
- excision of damaged DNA strand (XPD, XPB helicases)
- incision of DNA strand (XPF, XPG incisionases)
- DNA synthesis and ligation (with replication machinery)
what are the 2 forms of NER repair:
- transcription coupled repair (TCR)
- global genomic repair (GGR)
what is transcription coupled repair (TCR)?
-targets transcriptionally ACTIVE genes
-“fast” repair
-RNA polymerase II works in conjunction with the XP proteins to remove UV damage
-uses CSA and CSB (transcription factors?)
the TFIIH complex is carried with the RNA polymerase II, TFIIH system is “built into” RNA polymerase
what is global genomic repair (GGR)?
-uses the NER pathway (not built-in)
-slow repair of UNTRANSCRIBED regions
-removal of DNA damage can take days
why is the double strand break repair process important?
A double-strand break repair model refers to the various models of pathways that cells undertake to repair double strand-breaks (DSB). DSB repair is an important cellular process, as the accumulation of unrepaired DSB could lead to chromosomal rearrangements, tumorigenesis or even cell death.
what are the 2 modes of double strand break repair?
- non-homologous end joining (NHEJ)
- homologous recombination (HR)
what are some causes of double strand breaks (DSB)?
ionizing radiation
fork collapse
oxidative damage
drug induced damage
what are the 2 main signaling kinases and DSB damage sensors?
ATM
ATR
**MRN complex interacts with ATM and ATR directly and indirectly. it is the primary sensing complex for DSB. regulates cell cycle and initiates the repair of DSB.
what cells do NHEJ target?
cells at any stage of the cell cycle
what cells do HR (homologous recombination) target?
replicating or G2 cells
describe the NHEJ process:
- end recognition of the DSB by Ku heterodimers
- additional proteins recruited (DNA protein kinase K)
- processing of DNA ends, limited repair synthesis, and ligation
- end product = repaired DNA that has suffered a deletion of nucleotides
what is the downside of NHEJ?
DNA can be lost
think fast, half hazard, and nonspecific!
describe the homologous recombination process?
-occurs during S and G2 phase
-slower process than NHEJ (think slow and regulated)
-for sister chromatids
- MRN complex detects DSB
- exonuclease degrades 5’ ends
- strand invasion at branch point
- DNA synthesis and migration of branch point
- continued branch migration with pairing of newly synthesized DNA with the synthesis of the top strand
- DNA ligation
- DSB is accurately repaired
what would happen if there was a mutation in the DSB repair proteins?
MRN complex proteins: MRE11, Rad50, NBS1
ATM, ATR
mutation in these genes would have an negative impact on:
-sensing for DSBs
-cell cycle regulation (checkpoint repairs)
-transcription of DSB genes
-initiating repair of the DSB genes
how are BRCA1 and BRCA2 related to the HR pathway?
BRCA1: ubiquitin ligase, works directly in HR repair, tumor suppressor, transcription factor
BRCA2: promotes HR repair and recombination, activates the S phase checkpoint
both promote HR repair and ensure that there are not any double stranded breaks present prior to DNA replication (S phase)
what are the phases of the eukaryotic cell cycle?
G0: resting phase when cell has left the cell cycle and has stopped dividing
G1: cells increase in size, G1 checkpoint ensures that everything is ready for DNA synthesis, ensures there’s no DNA damage
S: DNA replication occurs
G2: gap between synthesis and mitosis, cells continue to grow, G2 checkpoint ensures everything is ready for mitosis
M: CELL GROWTH STOPS and cellular energy is focused on division into x2 daughter cells; metaphase to anaphase transition checkpoint (making sure spindle fibers are correctly attached)
phases of meiosis:
meiosis I and II
prophase: chromosomes condense, nuclear membrane disintegrates, find sisters and tetrads form (crossing over)
metaphase: migrate to metaphase plate
anaphase: tetrads split, chromosomes pulled to either pole by spindle fibers
telophase: cleavage furrow forms, cytokinesis
difference between anaphase I and anaphase II?
anaphase I - 2 TETRADS line up in the middle, and whole chromosomes are pulled apart
anaphase II - a chromosome lines up in the middle, the axis divides it into 2 SISTER CHROMATIDS
mitosis phases:
prophase
metaphase
anaphase (sisters are pulled apart, like meiosis II)
telophase
differences in mitosis and meiosis:
mitosis (cellular division): cell division (2n–>2n)
meiosis (reductional division): reproductive, gamete producing
(2n –>n)
what are the 2 types of cell death?
necrosis and apoptosis
morphological features of apoptosis:
-PROGRAMMED cell death
-can be intrinsic (stress) or extrinsic (induced by an external cell, i.e. macrophage)
-cell loses structure and the membrane blebs
-blebs are phagocytosed (cleaned up)
-NON-INFLAMMATORY
-controlled
-energy required
morphological features of necrosis:
-cell death due to injury or disease
-NOT PROGRAMMED
-external (e.g. infection) or internal triggers (e.g. ischemia)
-MESSY
-cell bursts and decomposes
-triggers INFLAMMATORY response
-passive/no energy needed
-debris is ultimately phagocytosed
what is common between the intrinsic and extrinsic apoptotic pathways?
both pathways eventually rely on caspase proteolytic cascades to achieve cell death
what is the differences between the intrinsic and extrinsic caspases?
intrinsic - caspase 9
extrinsic - caspase 8
BOTH have caspase 3 as the last step
describe the intrinsic apoptotic pathway:
- apoptotic stimulus disrupts the mitochondrial membranes (Bax and Bak poke holes)
- cytochrome C is released into the cytosol (also releases SMACS - apoptosis inhibitors)
- Cytochrome C binds to ATP and APAF-1 —> apoptosome
- procaspase 9 –> caspase 9
- caspase 3 activated
describe the extrinsic pathway process for macrophage interaction:
- external cell initiates apoptosis via signaling proteins
- signaling proteins (i.e. TNF-alpha - inflammatory cytokine) bind to death receptor on membrane
- cytosolic part of death domain dives deep into the cell (the death domain)
- death inducing signaling complex - DISC (FADD and TRADD) change shape and binds numerous proteins to form signaling complex
- procaspase 8 –> caspase 8
- caspase 3 activated
how is the extrinsic apoptotic pathway different for cytotoxic T cells:
T cell recognizes that the cell is expressing foreign antigens on its surface (MHC1)
Fas ligand (of T cell) binds the Fas receptor on the cell.
Changes the shape of the death domain signaling complex (DISC-FADD)
Same caspase pathway (caspase 8 –> caspase 3) as macrophage initiated.
what is a mutual part of the macrophage initiated and T cell initiated apoptotic pathways:
-both cause the death domain to bind to other proteins to form the DISC
-both initiate the same caspase cascade (caspase 3)
what is normal flora?
refers to the microorganisms including bacteria, fungi, and viruses that inhabit the human body or live on its surfaces
normal microbiota = normal flora = not harmful
why is the normal flora important?
-aid immune system in preventing infection
-key role in metabolism (GI)
-necessary for survival
what is symbiotics?
-live in harmony with their human host
-“mutualism”
-human body provides benefits necessary for bacteria’s survival and the bacteria offers benefits to the host
-e.g. symbiosis in the gut
what is an opportunist?
-potential pathogens that would not normally inhabit the body but can take advantage of an opportunity to
-in times of weakened immune responses or skin breaks
-cancer chemotherapy, anti-rejection drugs, catheter or central line insertions
what is a pathobiont?
-typically a benign endogenous microorganism
-potentially pathogenic and may cause disease when overgrowth occurs
-e.g. C diff - usually present in GI tract and is usually kept in check by other bacteria. Growth spurt after antibiotics. Causes toxin release and inflammation, colitis, diarrhea, abd pain, fever. Has endospores that can survive the stomach.
what is the role of human intestinal microbiota in health and disease?
GI tract bacteria keep one another in check
Prevents overgrowth
e.g. C diff infections
what is the predominant normal flora of the skin?
staphylococcus epidermis
what is the predominant normal flora of the nose?
staphylococcus epidermis, colonizing staph aureus
what is the predominant normal flora of the oropharynx?
viridians group
S mitis
S mutans
what is the predominant normal flora of the mouth?
streptococcus mutans
what is the predominant normal flora of the colon?
bacteroides fragilis (anaerobe)
E coli (faculative)
what is the predominant normal flora of the vagina?
lactobacillus, also colonized by group B strep (S agalactae) and E coli
what is tissue tropism?
pathogens and normal flora exhibit a PREFERENCE for specific tissues to live and grow
bacterial tropism is primarily driven by:
-tissue pH
-metabolic products
-immune factors
-oxygen levels
-other local tissue environmental factors
viral tropism is largely driven by host cell receptors that allow the virus to attach to the cell
what causes dysbiosis:
normal flora imbalance
causes:
-overgrowth
-too few bacteria
-inappropriate types
examples of dysbiosis in the gut:
small intestinal bacterial or fungal growth
-Klebsiella species (not normally present) found in the feces of IBS or gastroenteritis patients (indicating dysbiosis)
-alcohol induced dysbiosis can weaken the body’s defenses against Klebsiella pneumoniae (normally in mouth and skin), leading to PNA
example of dysbiosis in the vagina:
low pH maintained by Lactobaccillus
If Lactobacillus is decreased (i.e. Abx treatment), pH rises and potential pathogens can grow
yeast infection - Candida albacans overgrowth
BV - Lactobacilli replaced by Gardnerella vaginalis
examples of dysbiosis in the oral cavity:
normal bacteria: diptheroids and corynebacterium (overgrowth is harmful)
Pseudomembranous pharyngitis: C diphteriae proliferation due to oropharyngeal dysbiosis
creates a pseudomembrane = thick, grayish adherant exudate formed by cell debris and inflammatory products
normal blood pressure:
normal systolic: 120
normal diastolic: 80
what are the 3 factors that affect blood pressure?
- cardiac output
- fluid volume in the artery
- degree of constriction by arterioles (resistance)
what is blood pressure?
force of blood pressing against the artery walls
systolic vs diastolic pressure
both in relation to AORTA PRESSURE:
systolic: maximal contraction of the heart, aortic valve is open and blood is pushed into the aorta
diastolic: minimum pressure in the aorta, aortic valve closed, no blood exits heart into aorta, blood moves away from aorta due to the lower downstream pressure
normal heart rate:
60-100 bpm
normal respiratory rate:
12-16 breaths per minute
normal body temperature:
97.7-99.5
~98.6 F / 37 C
pulse pressure equation:
PP = systolic - diastolic
what is mean arterial pressure (MAP)?
-average pressure throughout one heartbeat
-“cardiac cycle”
MAP = 1/3 Ps + 2/3 Pd
Heart is in diastole 2/3 of the time. Therefore, factoring in the phase lengths.
explain how a sphygmomanometer is used:
cuff pinches artery, release pressure:
blood first pushed through the artery, a whoosing sound is heard –> systolic (turbulent flow)
sound disappears, blood flows smoothly (laminar) down the pressure gradient because the artery is fully open –> diastole
cardiac output equation:
CO=stroke volume x HR
what is the effect of sympathetic activity on stroke volume, heart rate, and cardiac output?
increases HR and stroke volume, therefore increasing CO
CO=stroke volume x HR
sympathetic activity ______respiratory rate.
increases
what are some causes for increased sympathetic activity? how do they differ in their mechanisms?
exercise:
-stronger contractions of the heart
-increase SV and Ps
-increased heart rate
-increased CO
-CO physiologically and temporarily increased
stress:
-arterioles vasoconstrict, increased Pd
-heart needs to beat stronger to overcome resistance, increase SV, increase Ps
-increased HR
-chronically and pathologically increases
respiratory buffer equation:
CO2 + H2O –> H2CO3–> HCO3- + H+
effects of high and low respiratory rates:
high:
-more CO2 removed
-less H+
-pH increases, alkalosis
low:
-less CO2 removed
-increase in H+
-pH decreases, acidosis
what are the 2 sources of internal body heat?
- metabolism (waste heat, non-shivering thermogenesis)
- muscle contractions (shivering thermogenesis, waste heat)
factors affecting human body temperature:
-age
-gender
-time of day (lowest at night)
-time in menstrual cycle (higher from ovulation to menses)
-state of consciousness and emotions
what are the different regions temperature can be taken? benefits/cons?
forehead: affected by environment, no body contact, quick
aural (ear): useful except during extremes
oral: 0.5 lower than rectal
axillary: too variable
rectal: most accurate for core body temperature, inconvenient
body water is ______% of total body weight.
60
lower in obese, higher in lean people
higher in infants, lower in elderly
what are the distributions of body water into compartments?
ICF: 66%
ECF: 33% (1/4 in plasma, 3/4 in interstitial fluid)
hydration status effects on the body:
ICF swelling: HA
ICF shrinking: fatigue
ECF depletion: hypotension
ECF overload: edema
effects of sodium on water weights:
water can freely diffuse between ICF and ECF. 33% kept in the ECF due to osmotic pressure created by sodium salts
how does a low sodium diet decrease BP?
salt in the blood stream increases water pressure in the arteries, therefore increasing pressure.
want the opposite effect.
how does a low sodium diet decrease BP?
salt in the blood stream increases water pressure in the arteries, therefore increasing pressure.
want the opposite effect.
stages of linear growth:
-prenatal
-infancy
-childhood
-adolescence
-adulthood
-aging
what is human linear growth?
period of time starting from the cleavage of the zygote (pre-natal) marked by the end of long bone growth (adolescence)
-long bone growth finished when estrogen is secreted, causing the epiphyses to fuse (growth plates)
compare the relative linear growth velocity during each stage of
human life cycle:
fetal and infantile: highest growth rate, environment, nutrition, health and happiness
childhood: sharply decreases and levels off but contributes 40% to adult height, growth and thyroid hormones present, genes, environment
pubertal: females have a peak slightly earlier than males, due to hormones (sex and growth), 15% of adult height
contrast hormonal control of neonatal growth to post-natal growth:
IGF 1 and 2 in pre-natal environment. pre-natal growth depends mostly on maternal size and uterine development. infancy is marked by the dependence of genetic factors. also thyroid hormones and infant environment and nutrition.
contrast hormonal control of neonatal growth to post-natal growth:
hormones predominate in post-birth ???
neonatal depends on uterine environment
infants: thyroid hormones
childhood: thyroid and growth hormones
pubertal: growth and sex hormones
Describe differences between genetic and environmental factors contributing to
aging
GENETIC:
-DNA repair defects - accumulation of mutations
-genetic abnormalities - abnormal cellular signaling
ENVIRONMENT:
-environmental insults - free radial damage
-reduced enzyme activity
-accumulation of damaged cellular proteins and organelles
innate vs adaptive immune responses
innate: protection against infection that relies on a mechanism that existed before the infection, capable of a rapid response of microbes
adaptive: protection against infection that is mediated by lymphocytes and is stimulated by exposure to FOREIGN antigens. specificity for distinct molecules and long-tem immunity. AKA “acquired immunity”
properties of the adaptive immune response:
-specificity
-diversity
-memory
-clonal expansion
-specialization
-contraction and homeostasis
-non-reactivity to self
where do B lymphocytes mature?
bone marrow
where do T cells mature?
thymus
what are all lymphocytes derived from?
hematopoietic stem cells
what are the 3 stages of lymphocytes:
1) naive cell - haven’t found antigen yet
2) activated/effector - encounters antigen, proliferates and carries out effector function
3) memory - immunological memory, quicker and more effective response with reinfection
what is clonal selection?
every person has a vast number of unique clonally derived lymphocytes
“immune repertoire”
each clone is genetically distinct and created at random, each expresses ONE pre-determined antigen receptor
clonal selection explains how a single B or T cell that recognizes an antigen that enters the body is selected from the pre-existing cell pool of differing antigen specificities and then reproduced to generate a clonal cell population that eliminates the antigen.
clonal selection occurs IF and ONLY IF _________.
a specific antigen enters the body and encounters a lymphocyte with that same specific receptor
role of antigen presenting cells (APCs):
-capture antigens, process antigens, and present them to lymphocytes for more sophisticated immune functions
dendritic cells
macrophages
B lymphocytes
innate vs. adaptive immunological memory
innate - very little/nonexistent
adaptive - memory T and B cells, enhanced secondary responses
primary vs secondary immune responses
primary:
-first encounter with antigen
-induces production of plasma cells - antibodies
-LAG period before antibodies produced
-modest production
secondary:
-second encounter with antigen (B cells are no longer naive)
-faster response
-produces antibodies at a higher rate and maintains the higher levels
what is humoral immunity?
adaptive defense mechanism mediated by B lymphocytes
antibodies produced
principal defense against EXTRACELLULAR microbes and toxins
what is cell mediated immunity?
adaptive defense mediated by T lymphocytes
Helper T cells -secrete cytokines that recruit/activate phagocytes to kill
Cytotoxic T cells - directly kill
list the phases of the immune response:
- recognition (antibodies for B cells, through APCs for T cells)
- activation phase (clonal expansion/differentiation/gain effector fx)
- antigen elimination phase
- contraction phase (return to homeostasis)
- memory phase
describe the chronological process of hematopoiesis:
image
what are the primary lymphoid organs?
bone marrow
thymus
secondary lymphoid organs:
spleen
lymph nodes
name some other secondary lymphoid tissue:
MALT - mucosa associated lymphoid tissue
GALT - gut associated lymphoid tissue
the site for presentation and initiation of immune responses against BLOOD BORNE antigens?
spleen
therefore, a splenectomy would be associated with a predisposition for certain blood borne infections, especially of encapsulated bacteria (S pneumoniae)
also a reservoir for RBCs, lymphocytes, and monocytes
describe the 3 different subdivisions of the spleen:
white pulp - immunologically active part
-periarteriolar lymphoid sheaths (PALS) - arteriolar supply of the spleen
-lymph follicles - dividing B lymphocytes
red pulp - hematologically active part
-most mass
-reserve storage of monocytes
marginal zone - in between the pulps
-contain the APCs (macrophages and dendritic cells)
describe the role of MALT:
MALT = lymphoid aggregates that sit near the entrances of the digestive and respiratory tracts
MALT on the tonsils
- M (microfold) cells on surface detect pathogen
- activate tonsillar B cells
- proliferate in the germinal areas
- secrete IgA antibodies
what are Peyer’s patches?
collection of lymphoid nodules found in the gut mucosal tissue
lymphoid nodules = small localized collection of lymphoid tissue located in the connective tissue beneath the epithelium
Peyer’s patches located in the ileum (SI)
-like MALT, contain M cells
-M cells detect antigen and transport into cell to the DCs
-DCs present antigen to lymphocytes
-T lymphocytes and Igx leave the efferent vessel - go to site of infection
passive diffusion is dependent on:
- concentration gradient
- partition coefficient
- cell surface area
- pH differences for ionic compounds
characteristics of active transport:
requires energy
moves drugs AGAINST electrochemical gradient
saturable (can saturate the channels)
selective (charge and size)
drugs can compete for transport
factors that effect the transfer of drugs across a membrane:
- molecular size
- partition coefficient
-(concentration of drug in lipid)/(concentration of drug in water)
-p>1 lipophilic
-p<1 hydrophilic - ionic character
-non-ionized can cross membranes (unless there’s an ion channel)
-chemicals exist in an ionized form when exposed to an environment with the opposite pH - effects of pH - Henderson Hasselbalch
a _______intravenous diffusion rate, promotes the absorption of a drug.
rapid
describe drug permeability of the CNS:
endothelial cells of CNS do not contain large pores (do not transmit ionized/large polar drugs)
therefore, lipid soluble drugs readily permeate the CNS membranes
what are the 3 types of drug reservoirs:
plasma proteins (albumin and alpha-1 glycoprotein)
tissues (prolongs drug action)
fat (lipid soluble reservoir)
what type of drugs does albumin bind?
acidic
what type of drugs does alpha-1 glycoprotein serve as a carrier for?
basic drugs
what are the 2 ways that drugs are eliminated in the body?
excretion - kidneys (unchanged drugs)
metabolism - liver (changed into metabolites)
describe the function of the liver in drug metabolism?
kidneys are modest (can’t excrete lipophilic drugs as they can be reabsorbed/pass through the membrane)
the liver makes these drugs more hydrophilic so that they remain in the urine and are excreted. also terminates their pharmacological activity
what enzymes catalyze phase 1 reactions in liver metabolism?
cytochrome P450 enzymes (family of CYP enzymes)
what are the differences between phase 1 and phase 2 of liver metabolism?
phase 1 - hydrolysis, oxidations, reductions
phase 2 - glucoronidation, sulfation
what are the 4 ways an drug can cross a membrane?
- passive diffusion
- active diffusion
- aqueous diffusion
- transporter
list the 6 types of biological drug receptors:
water and ions (nonspecific, i.e. laxatives)
metal ions (chelating drugs, i.e. chelating poisonous ions)
enzymes
nucleic acids
membrane sterols
specific receptors (i.e. Ach receptors)
what is affinity (drugs)?
tenacity for which a drug binds its receptor
what is intrinsic activity (drugs)?
capacity of a drug to propagate a biological signal
what is the structure activity relationship (SAR)?
affinity and intrinsic activity are closely related to the drug’s chemical structure
therefore, small modifications in the drug can drastically change its properties
what are the 2 receptor domains?
binding domain - binds ligand
effector domain - propagates signal (direct or through second messengers)
describe how steroid receptors enact a change:
- steroid drug passively crosses membrane and binds steroid receptor
- receptor activated and moves across nuclear membrane
- steroid binding induces conformational change in receptor, allowing it to bind response elements on DNA
- mRNA transcription and translation
- protein synthesis –> biological effect
**can also inhibit protein synthesis
examples of enzyme linked receptors:
tyrosine kinase
adenlyl/guanlyl cyclases
examples of enzyme linked receptors:
tyrosine kinase
adenlyl/guanlyl cyclases
**have ligand binding domain and intracellular catalytic domain
explain receptor desensitization:
continued stimulation of cells with agonists generally results in desensitization
-down regulation of receptors on the membrane
e.g. repeated use of bronchodilators in asthma treatment
explain supersensitivity (up-regulation) of receptors:
supersensitivity to agonists frequently follows a chronic reduction in receptor stimulation
with chronic inhibition, there is an upregulation of receptors
when inhibitor is removed, there are now more receptors available for drug binding
e.g. long term use of B adrenergic drugs such as propanolol. stop propranolol and will get hypersensitive B adrenergic response
what causes myasthenia gravis?
autoimmune depletion of Nm receptors
(type II hypersensitivity - autoantibodies bind Ach receptors on skeletal muscle cells)
what causes some forms of IDDM?
autoimmune depletion of insulin receptors
(type IV hypersensitivity)
effect of propanolol on B adrenergic receptors?
propanolol = beta blocker
B adrenergic receptor agonists used in asthma treatment but can become desensitized with long term use
if patient receives long term administration of propanolol and then stops taking the drug, hypersensitivity to the B adrenergic asthma drugs may be seen
types of bonds between drug and receptor (in order of decreasing strength)
covalent
ionic
H bonds
hydrophobic
van der waals
what is the receptor occupancy theory?
- response occurs in receptor when drug is bound
- more receptors bound = greater response
- all receptors bound = maximal response
what is the ED50 or EC50?
concentration or dose of drug that causes half of the maximal response (all receptors bound)
AKA the potency
what does the dose-response relationship look like graphically?
image
what does the dose-response relationship look like graphically?
image
what are antagonists?
binds receptors without causing an effect but blocks the binding of endogenous agonists
therefore, have affinity but not intrinsic activity
what are the three types of antagonism?
competitive
irreversible
uncompetitive
what is physiological antagonism?
drug response mediated by the activation of a receptor is counteracted/opposed by the opposite response produced by another DIFFERENT receptor
e.g. epinephrine and anaphylaxis
histamine causes vasodilation, epinephrine is given to overcome hypotensive effect
contrast graded and quantal responses
graded response: the more receptors bound, the greater the response (receptor occupancy theory)
quantal response: an all or nothing response. as dose is raised, population affected is raised (e.g. desired effect is absence of seizure, adverse affect is death)
equation for therapeutic index:
TI = (LD50)/(ED50)
LD50 - median lethal effective dose that kills 50% of subjects
ED50 - median effective dose that protects 50% of subjects
therapeutic index = DRUG’S MARGIN OF SAFETY
what kind of therapeutic index is desirable?
a high therapeutic index is good
means there’s a large difference between the lethal and effective doses (e.g. penicillin)
a low therapeutic index is bad
not much difference, very easy to overdose
e.g. warfarin and digoxin
examples of decreased responses in dose-responses
tolerance - repeated exposures to a drug lead to diminished response (down reg of receptors)
tachyphylaxis - rapid loss of response upon repeated exposure to a drug (down reg of receptors)
resistance - diminished response to drugs that inhibit cell growth or death
examples of increased dose relationship responses:
additive - two drugs given together are equal to the sum of their individual effects
synergism - response is greater than the sum of individual effects
potentiation - administration of a drug with little/no effect enhances the effect of another drug
what is pharmokinetics?
study of the processes of absorption, distribution, and elimination of drugs as they relate to the time course of the drug’s presence in the body in one or more compartments
what is the fundamental hypothesis in pharmacokinetics?
a relationship exists between the pharmacologic (toxic) effect of a drug and its concentration in the blood
most assays do not distinguish _______from _______, therefore, the total drug concentration in the plasma includes both.
free drug, bound drug
the extent of binding and the fraction of free is relatively constant
what is first order kinetics (drugs)?
the rate of decrease in drug concentration over time is directly proportional to the drug concentration
high drug concentration - faster elimination
as drug concentration decreases - slower elimination
what are the 2 assumptions in pharmacokinetics?
-first order kinetics
-the body can be treated as a single compartment
what is bioavailability (F)?
fraction of the unchanged drug that reaches systemic circulation
for IV drugs…F=1
explain zeroth order kinetics:
the elimination of drug is constant and INDEPENDENT of concentration or the amount of drug
occurs when the system is rate limiting or a saturable process
e.g. alcohol dehydrogenase becomes saturated and then can only metabolize 9g/hr, regardless of concentration
**can’t use any of the pharm equations
karyotyping involves freezing chromosomes during which phase of mitosis?
metaphase - most visible
what cell type is ideal for karyotyping?
WBCs - enter mitosis easily when stimulated
describe the karyotyping process for WBCs:
- WBCs from blood sample are cultured in the presence of growth factors
- arrested in metaphase using COLCHICINE
- added to a hypotonic solution to swell
- cells fixed with EtOH/acetic acid
- stained with Geimsa stain
describe Geimsa staining (G banding) patterns:
dark bands
-heterochromatin
-stain binds A-T regions strongly
light bands
-euchromatin
-loosely packed chromatin
-stain does not bind G-C strongly
-gene rich regions
3 centromere placements:
metacentric (p and q almost equal)
submetacentric (p arm is shorter)
acrocentric (p arm is very short)
euploid
having the normal number of chromosomes
polyploidy
presence of a complete extra SET of chromosomes
eg. triploidy (3N), tetraploidy (4N)
possible mechanism of triploidy:
fertilization of one egg with two sperm
causes fetal loss in first 2 trimesters
possible mechanism of tetraploidy
fusion of 2 diploid zygotes or mitotic failure
rare
aneuploidy
missing or additional INDIVIDUAL chromosomes
monosomy
only have one copy of a chromosome pair
nearly always leads to death
critical loss of genes
what is turner syndrome?
genetic female missing an X chromosome
45 XO or 45X
trisomy
presence of an extra chromosome
more compatible with survival than monosomy (no critical loss)
what are the 3 trisomies:
trisomy 13 - Patau (lucky 13/ st. patrick)
trisomy 18 - edwards (stephanie edwards has wanted to become a doctor since she was 18)
trisomy 21 - down syndrome
what is klinefelter syndrome?
47, XXY
genetic male due to Y presence but has an extra X
calvin klein, a man who’s into fashion
clinical features of down syndrome:
depressed nasal bridge, upslanting palpebral fissures, epicanthal folds
congenital defects in 40%
moderate to mild ID
what other disease is down syndrome linked to?
alzheimer’s
aberrant gene expression of amyloid precursor protein (APP) on chromosome 21
3 causes of down syndrome:
nondisjunction during meiosis I in the female (90%)
nondisjunction during meiosis I or II in male (10%)
OR
robertsonian translocation involving chromosomes 21 and 14 (4%)
what is the karyotype for a robertsonian translocation in a person with down syndrome?
45, XX/XY, t(14;21)
long arm of chromosome 21 translocated to the long arm of chromosome 14
short p arms lost
result: loss of one chromosome
result of nondisjunction in meiosis I:
trisomy
trisomy
monosomy
monosomy
result of nondisjunction in meiosis II:
euploid
euploid
trisomy
monosomy
what is a 1st trimester US looking for (down syndrome)?
nuchal translucency (NT)
elevated NT indicates high risk for DS
2nd trimester down syndrome US looks for…
major anatomic abnormalities
cleft lip, polydactyly, abdominal wall or cardiac irregularities
what two serum biomarkers are elevated in maternal labs (down syndrome)?
B-hcg
inhibin A
what is a translocation?
rearrangements between segments of NON-HOMOLOGOUS chromosomes
can be balanced or unbalanced
can be reciprocal, nonreciprocal, or robertsonian
what is a robertsonian translocation?
results in the fusion of long arms of acocentric chromosomes
the 2 p arms are lost (usually no clinical significance)
what are the acocentric chromosomes?
13, 14, 15, 21, 22
3 types of deletions
terminal deletion (end of chromosome)
interstitial deletion (within chromosome)
microdeletion (very small, need FISH to see)
cri-du-chat
crIIII-FIIIIve
deletion of the SHORT arm of chromosome 5
46, XX/XY, 5p-
symptoms of cri du chat
high pitched CRI
microcephaly, ID, associated with cardiac abnormalities
williams syndrome cause:
deletion of long arm 7
symptoms of williams syndrome
“WL always had extreme friendliness with strangers”
ID, distinctive facial features, increased sensitivity to vitamin D, high calcium levels, cardiac abnormalities sometimes
pericentric vs paracentric inversions
chromosome inversions
para - do not include centromere
pericentric - involve the centromere
2 most common ring syndromes:
14, 21
how does a ring chromosome form:
deletions on either end of the chromosome create “sticky” ends
attach to each other
ring is typically lost, leading to monosomy
isochromosome cause:
chromosomes divide along axis that is perpendicular to the normal
lethal loss of genes
cause of Edward’s syndrome
trisomy 18
isochromosome 18q
produces an extra long arm of chromosome 18
results of unequal cross over?
variable number tandem repeat (VNTR) polymorphisms, deletions, duplications
types of microscopy
light microscope
-uses light (photons)
-cells or tissues on slides
-stained with something to give color/contrast
electron microscopy -uses electrons:
- transmission electron microscopy (TEM)
2D
VERY THIN sections, stained with metal for contrast - scanning electron microscope
sample coated in metal
electrons produce a 3D image - freeze fracture (a type of TEM)
light microscopy - cytospin vs blood smear
cytospin - cells centrifuged into a circular area
blood smear - blood is dragged along to smear it on the slide
2 locations of goblet cells:
digestive or respiratory systems
what are the 2 dyes commonly used - what colors do they stain
eoisin
-acidic/eosinophilic
-stains basic features PINK
-stains PROTEINS/CYTOPLASM
hematoxylin
-basic/basophilic
-stains acidic structures BLUE
-stains NUCLEI
what is freeze fracture
membranes are “fractured” of split in between 2 layers of the lipid bilayer
type of TEM but appears to be 3D
ALWAYS shows membrane structure
composition of whole blood:
erythrocytes (44%)
hematocrit = volume % of RBCs in blood
plasma (55%)
water, proteins, other solutes
buffy coat (<1%)
platelets, leukocytes
types of monocyte derivatives:
langerhan’s - skin
kupffer - liver
dust - lungs
microglia - brain
osteoclasts - bone
what are the charged AAs?
glutamic acid (E)
aspartic acid (D)
arginine (R)
lysine (K)
histidine (H)
which AA has buffering capacity?
histidine
pka=6.2
aspartate effector function
excitatory nt
glycine effector function
inhibitory nt, heme precursor
arginine effector function
urea and nitric oxide precursor
glutamate effector function
excitatory nt, precursor of GABA (inhibitory)
histidine effector function
precursor of histamine (inflammatory)
tryptophan effector function
precursor of serotonin, melatonon
tyrosine effector function
hormones and catecholamine precursor (epinephrine, norepinephrine, dopamine, thyroxine)
heat shock protein (HSP) function
helps with protein folding
needs ATP
chaperone “cage” with 2 stacked rings
protein enters hydrophobic cage
folded and is released
describe the process of amyloid formation in alzheimer’s:
- transmembrane portion of amyloid precursor protein is cut
- spontenous aggregation of the amyloid pieces (AB)
- forms insoluble fibrils of B pleated sheets
Beta sheets are Bad.
describe how prions (PrP) lead to disease:
- infectious PrP has beta sheets
- PrP interacts with noninfectious PrP (alpha helix)
- healthy PrP converts into infectious (beta sheet)
- goes on and does the same (exponential infection)
healthy - alpha
unhealthy - beta
Beta sheets are Bad.
2 possibilities for buffers:
weak acid with conjugate base
weak base with conjugate acid
2 possibilities for buffers:
weak acid with conjugate base
weak base with conjugate acid
what are the 2 protein degradative pathways for damaged or unneeded proteins:
ATP dependent ubiquitin proteasome system
-cytosol
-endogenous proteins
-damaged proteins
-MHC1
ATP independent lysosomes
-extracellular proteins/phagocytosis
-plasma proteins
-organelle recycling
-MHC2
stomach acid is secreted by _________. it’s function is to__________.
parietal cells
denature proteins, making them more susceptible to proteases
Acid - pArietal
______secretes pepsinogen in the stomach which is converted to active form (pepsin) by _______.
chief cells, HCl (or automatically)
role of pepsin
creates peptides and a few free AAs (breaking down the protein)
where does zymogen activity take place (protein degradation)?
zymogen enzymes secreted by the pancreas break down oligopeptides into amino acids in the small intestine
what enzymes are secreted by the small intestine (protein degradation)?
di and tri peptidases
amino peptidases
3 types of AA branched chain metabolism:
- transamination
- oxidative decarboxylation
- dehydrogenations
what causes methylmalonic acidemia?
defects in the methylmalonyl mutase gene
defects in genes that are responsible for conversion of cobalamin (vit B12)
splicing process:
mediated by snRNPs in the splicesome
- 5’ ss donor binds to branch point A
- intron lariat is formed
- 3’ ss acceptor site broken
- lariat discarded, exons ligated together
describe how RNA processing is cotranscriptional:
RNA processing can add to transcriptional stability
therefore, want want processing to occur as transcription is taking place, before splicing occurs. splicing would just remove these modifications prior to translation.
e.g. inserting intronless genes into intronless versions of intron dependent genes
would want to insert the introns into the 5’ UTR
why?
-don’t want it to be expressed (just there for stability)
-want it down at 5’ end rather than 3’ because RNA is processed from 5’ to 3’ and you want STABILIZATION at the beginning
overall, if these modifications aren’t added during transcription, they’re just gonna be spliced out after the fact and then there would be no point for having them anyways.
describe the RNA interference (RNAi) silencing process:
- DICER recognizes dsRNA (i.e. viruses)
- breaks the dsRNA into pieces (small interfering RNAs)
- 1 siRNA enters the RISC complex
- associates with the argonaute protein
- finds this small sequence in host and degrades it
- RNA virus genome degraded and infection stops
** can introduce in a lab setting to knock out genes, therapeutic
what does alternative splicing in the untranslated regions (UTRs) lead to?
does not alter protein structure (not involved with exons)
however, may alter mRNA levels and protein levels
remember, UTR modifications can alter stability
e.g. AU/AT rich regions are unstable, splice them out and will get more stability and higher protein levels
.
loss of function vs gain of function:
loss of function - inactive or less active protein
(e.g. thalassemias: anemia due to inefficient erythropoiesis)
gain of function - overly active protein
(e.g. thrombophilia/blood clots: too much prothrombin gene)
what are the types of mutations?
nonsense - immature stop codon
missense - point change, one AA changed for another
frameshift - addition or deletion changes reading frame
synonymous - mutation does not change AA
conservative - changes AA but new AA has similar biochemical properties as the original
what polymerase is involved in bacterial clonal replication?
DNA polymerase III
what are transposons?
allow for drug resistance genes to be transferred from plasmid to host DNA
they flank the sequence of interest and insert it into host bacterial DNA
what are high frequency recombinations (bacteria)?
plasmid incorporates itself into the donor DNA
then DNA is transferred to receiver
receiver gets some plasmid DNA along with host DNA
what does protein A (virulence factor) do?
binds IgG and prevents an immune response
e.g. staph aureus
role of IgA protease (virulence factor):
binds and degrades IgA antibodies
prevents IgA from recognizing pathogens in mucous membranes
role of M protein (virulence factor):
prevents opsonization/phagocytosis
has epitopes - confuses antibodies and causes the host cells to react to self-antigens that look similar to M protein - S pyogenes - rheumatic fever
penetrance vs expressivity
expressivity - dimming lights (present but at varying extents)
penetrance (on/off switch) - how many individuals in a population with a certain genotype express the phenotype
what is mosaicsim?
a mutation that occurs AFTER fertilization
therefore, not all cells are affected
the earlier the mutation, the more cells affected
cascade effect
what is epistasis? what law does it contradict?
one gene effects the expression of another gene
e.g. baldness gene masks hair color gene (2 different genes)
disobeys law of dominance
allelic heterogeneity vs locus heterogeneity
allelic - different mutations on the same locus (same gene) lead to a similar phenotype
locus - variants on different loci (different genes) lead to a similar phenotype
what are the modifiable residues on N terminal histone sequences?
K - lysine
R -arginine
S -serine
T -threonine
explain histone acetylation:
histone acetyl transferase acetylates the amino acid residue
amino acid loses its charge
loosens the interaction with DNA
histone patterns:
acetylated - gene activation
non acetylated - gene inactivation
what DNA base is methylated?
cytosine
via DNA methyl transferases
therefore, large number of cytosines - likely to be a silenced gene. in the circumstance that a C is switched for T in the UTR region for example, would most likely increase gene expression.
DNA methylation _______ transcription.
silences
methylations are read by MBD (methyl binding domain)
DNA methylation DOES NOT effect base pairing
cystine 5’ demethylation/hydroxylation ________ transcription.
increases
what is the earliest signs of cell injury?
cloudy swelling
swelling of the organelles
rough ER becomes dilated - lose ribosomes
what is hydropic degeneration?
continued swelling of the organelles in response to injury
vacuoles appear in the cytoplasm
loss of basophilia
what is fatty change (steatosis)?
accumulation of triglycerides in the cytoplasm
common in the liver (fatty liver)
causes: toxins, hypoxia, alcohol
what are fibrotic changes?
irreversible changes
fibrotic bands visualized
cells die - necrosis
nodular appearance on the liver
atrophy/hypertrophy
decrease and increase in cell SIZE
cell count does NOT change
hyperplasia
increase in the number of cells
what happens to the thymus during adulthood?
active at a young age, involutes before adulthood via APOPTOSIS
controlled cell death
what is an xanthoma?
intracellular accumulation of cholesterol within macrophages
clusters of foamy cells (lipid laden macrophages found in sub-epithelial connective tissue or skin and tendons
gross appearance - small plaques to large masses
