FOM Week 6 Flashcards
PML
A growth suppressor protein that induces cell death
RARalpha
Induces promyelocyte differentiation into specific WBCs
What happens in APL
There is a chromosomal translocation and the PML and RARalpha proteins become fused together through non homologous end joining
The fused protein now inhibits apoptosis and differentiation
How does retinoic acid/arsenic help to treat APL
It removes the PML-RARalpha protein from the DNA
Apoptosis and differentiation can now occurs
How do steroids affect the estrogen receptor
Steroids will diffuse into the cell and bind to the ER
This will then cause two ERs to dimerize and bind to a specific DNA sequence
This then recruits HATs for transcription
Bilaminar Embryo
Early on when the ICM divides into the epiblast and the hypoblast
Trilaminar Embryo
When the epiblast undergoes gastrulation to divide into the ectoderm, the mesoderm, and the endoderm
3 Stages of Pregnancy
Period of Ovum (fertilization-->blastocyst) Embryonic Period (implantation-->organogenesis) Fetal Period (week 9-->birth)
What happens when you scramble two different types of sponge cells
They will reaggregate into their groups
Like cells recognize like cells
Expression of CAMs
High during aggregation
Low during migration
Important for NC migration/aggregation
Expression of Fibronectin
Low during aggregation
High during migration
Important for NC migration/aggregation
Totipotent/Pluripotent/Multipotent Stem Cells
Totipotent stem cells can become any cell in the body. They end after the 4 cell stage
Pluripotent stem cells can become any cell in a certain germ layer
Multipotent stem cells can become any cell of a certain lineage belonging to a germ layer
Differentiation
The process of restriction and determination resulting in a particular cell type with a specific function
Evagination vs Invagination
Evagination forms an outpocket of cells (eyes)
Invagination forms an ingrowth of cells (glands)
What two rxns must sperm undergo
Capacitation- removal of head proteins to expose receptors for binding to the oocyte
Acrosomal Rxn- digestive enzymes migrate through the zona pallucida
What two rxns follow fertilization
Cortical Rxn- cortical granules release lysosomal enzymes to prevent any sperm from passing
Zona Rxn- zona pallucida properties are altered to prevent sperm binding
Cleavage
Takes 3 days
The cell rapidly divides from 1 to 16 without increasing in size
Compaction keeps the cells close together
Morula
16 cell stage
The inner cells become the ICM
The outer cells become the trophblast (placenta)
Blastocyst
When the morula creates the ICM and the cavity
This is the structure that will undergo implantation once the zona pallucida hatches
After implantation, what happens to the ICM
It divides into the epiblast (columnar) and the hypoblast (cuboidal)
Ectopic Pregnancies
When the zygote implants somewhere other than the uterine wall
Usually leads to a miscarriage
Usually occurs in the ampulla of uterine tube or abdominal
Gastrulation
Occurs around week 3-4
Begins at the primitive streak and is organized by the primitive node/FGF
The process by which the germ layers are formed
Notochord
Forms from the endoderm in cranial to caudal direction around same time as gastrulation.
It is important for inducing the neural plate and ectoderm
How is the A-P axis defined
AVE expresses genes that define the anterior region
The primitive streak defines the posterior end
How is the D-V axis defined
BMP4 ventralizes the mesoderm
Chordin (activated by goosecoid), noggin, and follistatin dorsalizes the mesoderm and notochord
How do conjoined twins form
There is too little or too much goosecoid
Caudal Dysgenesis
Brachyrury gene is missing/mutated
Brachyrury is needed for cell migration/limb formation
How is the L-R axis defined
FGF8 is secreted by the node on the left side and establishes nodal
FGF8 on the right side is inhibited by SHH
Teratogenesis Associated with Gastrulation
During the 3rd week the embryo is very susceptible to teratogenic compounds
Alcohol can cause FAS at this stage
Sacrococcygeal Teratoma
When the primitive streak does not regress
Leads to a non malignant tumor on the fetus
Primary Villi
Secondary Villi
Tertiary Villi
1 is two trophoblast layers
2 is two trophoblast layers with a mesoderm core
3 is when capillaries become present in the core (3rd week)
Screening Tests
A form of secondary prevention that is usually done on healthy people who are displaying no symptoms
Meant to reduce morbidity and mortality
Criteria for a Screening Test to be Good
Disease has to have a high enough prevalence
Disease has to be treatable
Disease has to be accurately identifiable
Patient has to be okay with the form of screening
Lead Time Bias
The time from when the disease becomes detectable to when it can be diagnosed by symptoms
Lead time bias is extra time added onto the screened group
In reality screening has no effect on the course of a disease
Length Time Bias
Individuals with longer pre clinical conditions/phases are more likely to be detected by screening
Leads to overdiagnosis
Sensitivity vs Specificity
Sensitivity is the ability of a test to accurately identify those with the disease
Tests with high sensitivity often give false positives
Specificity is the ability of a test to accurately identify those without the disease
Test with high specificity often give false negatives
How to Calculate Sensitivity and Specificity
Sens= TP/(TP+FN)
Spec= TN/(TN+FP)
PPV vs NPV
PPV is the probability that disease is present given a positive result
PPV= TP/(TP+FP)
NPV is the probability that disease is not present given a negative result
NPV= TN/(TN+FN)
Likelihood Ratio
Likelihood of test result when disease is present divided by likelihood of test result when disease is absent
Sequential Testing vs Simultaneous Testing
Sequential involves a cheap first test that has a high specificity. If you test negative you stop. If you test positive you move on to the next
Simultaneous testing is used for large groups
If you test positive to one, you are positive
If you test negative to both, you are negative
Cell Types in the Epidermis
Keratinocytes
Merkel Cells (come from neural crest)
Langerhan Cells
Melanocytes (come from neural crest)
5 Layers of the Epidermis
Stratum Corneum Stratum Lucidum Stratum Granulosum Stratum Spinosum Statum Basale
Psoriasis
Normal turnover of the epidermis is 1-2 months
In psoriasis it is 3-4 days
This is due to localized inflammation and increased cytokines
Bullous Pemphigoid
Pemphigus Vulgaris
Pemphigus Foliaceus
BP is Abs that attack the hemidesmsomes
Pemphigus vulgaris is Abs that attack desmoglein 3 which is high in the basal layer
Pemphigus foliaceus is Abs that attack desmoglein 1 which is high in the corneum layer
Anagen
Catogen
Telogen
Anagen is hair growth
Catogen is intermediate/regression
Telogen is rest/shedding
Regeneration vs Scar Fomation
Regeneration occurs with mild cuts that do not pass the epidermis
Scar formation occurs with more severe cuts that go into the dermis
First Intention vs Second Intention Wound Healing
First only involves neutrophils, macrophages, and fibroblasts
Second involves those three but also myofibrilblasts to contract the ends of wound together
Skin Grafting
Used to accelerate wound healing and minimize the amount of fluid lost
Can be self or non self
Impact of Education on Health
The higher your education level, the more likely you are going to have better health
People who dont graduate high school have a 3 times higher mortality rate than those who do
Which county in KS has the best education
Which county in KS has the worst
Johnson County has the best. It also has the best health outcomes and the highest income
Wyandotte County has the worst eudcation
How does living in a rural area impact health
You have less access to quality care
You often have more risky occupations
Lots of rural areas have high poverty
How does living in an urban area impact health
Often the neighborhoods are less safe
Pollution
Often there is a poorer quality of food
Causes of Health Disparities
Opportunity Income Education Access Location
Derivatives of Ectoderm
CNS PNS Epidermis/Hair/Nails Mammary/Pituitary Glands NC Cells
High BMP4
Medium BMP4
Low BMP4
High produces epidermis
Medium produces NC cells
Low produces neural plate
Neuralation
Occurs during the 4th week
Part of the ectoderm becomes induced by the notochord to form the neural plate
Forms craniocaudally and it is when the neural plate folds
What happens when the neural plate does not close
Anencephaly when the cranial does not close Spina bifida when the caudal end does not close Folic acid (vitamin B9) can prevent this
Derivatives of NC Cells
Melanocytes Perkel Cells Facial cartilage and bone Smooth muscle PNS
NC Cell Migration
The NC cells undergo EMT
They exit the head before the tube closes and they exit the caudal end after the tube closes
Cause of Cranio-Facial Defects
Failure of the NC cells to migrate properly
HOX Gene Organization
3’ end has lower number
5’ end has higher number
Lower number genes are expressed in head region
Higher number genes are expressed in tail region
Derivatives of Endoderm
GI tract Respiratory Tract Urinary Tract Liver Pancreas Bladder
3 Stages of Adolescents
Early- puberty begins, they are concerned about body, they separate from family, concrete thinking
Middle- puberty is usually complete, some abstract thinking
Late- physical maturation complete, body image secure, develop life goals
Puberty in Girls
Takes about 4 years to complete
Is made up of 5 stages
Thelarche is the first step and begins with asymmetrical breast development
Puberty in Boys
Takes about 3 years to complete
Is made up of 5 stages
98% of time the first step is testes enlarge
Taking Adolescent History
HEEADSSS Home Education Eating Activities Drugs Sex Suicide Safety
Derivatives of the Paraxial Mesoderm
Somites
- Vertabrae/ribs
- Dermis
- Skeletal Muscle
- Limbs
Derivatives of the Intermediate Mesoderm
Urogenital Structures
-Kidneys
Derivatives of the Lateral Mesoderm
Heart/Blood Vessels
-Cardiac and smooth muscle
Formation of Somites
Somatomeres form craniocaudally. These will then form somites in pairs
They are transient structures but help to form the segments of the body
Formation of Kidneys
Occurs in the 4th week
Pronephric–> Mesonephric–> Metanephric
Two Layers of Lateral Mesoderm
Somatic/Parietal- ventral body wall/limbs
Splanchnic/Visceral- wall of the gut and heart
Vasculogenesis
De novo formation of new blood vessels
Stimulated by FGF2 and VEGF
Angiogenesis
Branching/extension of existing blood vessels
Stimulated by VEGF
Capillary Hemangiomas
Abnormal vascularization
Occurs in 10% of births and normally in facial area
Areas of Hematopoesis
Starts out in the yolk sac–> mesonephros–> liver/spleen–> bone marrow
Syndactyly
Fused digits due to failure of apoptosis
Examples of Apoptosis
Formation of digits
Control of cell number
Deletion of structures
Deletion of abnormal cells
Characteristics of Apoptosis
Chromatin condenses Membrane blebs DNA cleavage No energy required Phosphatydalserine redistributes membrane to signal macrophages
Extrinsic Pathway
An outside ligand binds to the death receptor
This recruits the initiator caspase8
Caspase8 will then activate other caspases and MOMP
Active Site of Caspases
To become active they have a sequence that needs to get cleaved
The active site is a cysteine protease that cleaves at Asp residues
IAPs
Inhibitors of apoptosis by binding to initiator and effector caspases
What happens once caspases are activated
Kinases become activated--> Ca influx Cytoskeleton breaks down PARP gets destruction--> no DNA repair DNA gets fragmented Nuclear lamin degrades Flippases become degraded
Intrinsic Pathway
Activated by cellular stress (DNA damage, heat, hypoxia, etc)
This activates P53 and BH3 proteins that inactivate the anti apoptotic BCL2 genes and activate the pro apoptotic BCL2 genes
BAX
Forms a pore in the mitochondrial membrane that disrupts the ETC and releases cytochrome C (MOMP)
Apoptosome
Cytochrome C forms a super complex with other proteins and this activates more caspases
Health Policy
A formal statement that defines priorities and parameters for action
Areas of Health Policy
Public Health Structural interventions Health care delivery Licensing of professionals Accreditation of health care providers
Sources of Health Policy
International/WHO
Government
Private Organizations
Trends of Public Health in US
Worst in the SE and improves as you move NW
US spends the highest % of GDP on health spending
How are free radicals generated
Normal cellular redox rxns Absorption of radiant energy (radiolysis of water) Neutrophils Fenton Rxn NO productions
Damages of ROS
Lipid peroxidation of membranes
DNA damage
Protein damage
Reperfusion
Caused by ischemia
These cells are more likely to produce ROS
Anti Apoptotic Proteins
BCL-2
BCL-XL
MCL1
Pro Apoptotic Proteins
BAX
BAK
BH3
Common Intracellular Accumulations
Fat (clear) Glycogen Lysosomes Iron (dark blue) Lipofuscin (yellow-brown) Melanin (brown-black) Hyaline (red) Carbon pigment (black)
GPCRs
Signal Transduction Receptor
Has a 7 transmembrane domain
On the cytosolic side there is a heterotrimer protein that initiates the cascade
Activation/Deactivation of GPCRs
Once the ligand binds it will induce a conformational change that will swap GDP for GTP. This causes the alpha subunit to dissociate from the beta/gamma unit. These two unit will then lead to downward actions
It is turned off by a GTPase that hydrolyzes the GTP and the units will then rejoin. This process is sped up by RGS
Ways to Inactivate the GPCR
Phosphorylate it and the G protein cannot bind
Hydrolyze the GTP
Block the ligand (ex is beta blockers)
Cholera/Pertussis
Cholera prevents the GTP from being hydrolized so the signal is not turned off
Pertussis binds the the alpha subunit of the Gi protein and prevents it from binding to the GPCR
