FOM Week 6
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Defintion: Amniotic Cavity
Fluid filled cavity surrounding the embryo
Immature prescursor cell
embryo stage at which blastocele (cavity) forms in ICM (inner cell mass)
cells of inner cell mass at blastocyst stage
Definition: Exocoelomic cavity
Primary yolk sac
Definition: Extra-embryonic coelom/chorionic cavity
portion of the coelom that extends beyond the embryo body
Definition: Inner cell mass (ICM)
the inner cells at the morula stage
Definition: Outer cell mass
the outer cells at the morula stage
cells of the outer cell mass at the blastocyst stage
Definition: Chorionic cavity
Surrounds the amniotic cavity
Definition: Yolk sac
has a small, indirect role in nutrition; becomes vascularized and nutrients are absorbed into blood for fetus
Why do we study embryology?
To help us understand normal development, embryological proceses recapitulated in adults, embryological components of diseases, and congenital malformations
What happens to the oocyte prior to fertilization?
- Oocyte is stuck in metaphase
- Zona pellucida surrounds it; follicular cells surround that; entire thing is called a Graafian follice
- Follicle ruptures when it connects to ovary wall; oocyte and zona pellucida move out
- Theca cells remaining in the uterus form the corpus luteum; secretes progesterone which thickens uterine wall and stimualtes secretory activity for implantation; if pregnancy occurs, the corpus luteum remains
- Oocyte is swept into uterine tube by finger-like prjections called fimbria
Uterine cilia, fluid movements, and flagella all aid the movement of what?
Before infiltrating the oocyte, the sperm must undergo what to reactions?
- Capacitation: takes 7 hours; allows the sperm to pass through corona cells surrounding the oocyte; removal of glycoprotein coat and seminal plasma proteins overlying the acrosome region; exposure of receptors on acrosome cap
- Acrosome reaction: leads to release of enzymes needed to penetrate the zona pellucida; capacitation reaction MUST happen first
Once the sperm has undergone the proper reactions, what happens?
- Sperm binds to zona pellucida through the mediation of ZP3; induces enzyme release from acrosome cap; sperm penetrates and contacts plasma membrane of oocyte; leads to fusion of sperm and oocyte cell membrane
- Cortical and zona reactions prevent polyspermy through the release of lysosomal enzymes from cortical granules lining oocyte membrane (cortical reaction) and the alteration of the zona pellucida to prevent further binding (zona reaction)
- When sperm is added, 2nd meiotic division is completed; introduction of 22 autosomes and sex chromosome; fusion of male and female pronuclei; replication of DNA; diploid cell
What has happend by 30 hours post-fertilization?
2 cell stage is reached
What has happened by 40 hours post-fertilization?
4 cell stage is reached
What critical event happens at the 8 cell stage?
- Compaction; cell-cell contacts are maximized; segregation of inner and outer cells; inner cells begin communicating via gap junction
- This is where the structure can first be called a blastocyst
What happends at 3 days post-fertlization?
- 12-16 cell stage
- Inner cell mass forms (embryo proper, amnion, yolk sac); also called the embryoblast; localizes to one pole; fluid penetration into intracellular space results in blastocele cavity formation
- Out cell mass forms (trophoblast); later contributes to the placenta and forms the surrounding, supportive tissue
What happens at 4 days, during the late morula stage?
deletion of zona pelluica, entry into uterine cavity
What happens at day 6 post-fertliziation?
- Implanation of the blastocyst; this is mediated by cell-cell and cell-ECM interactions
- the trophoblasts at the embryonic pole penetrate uterine endometrium; usually occurs on the anterior/posterior portions of the uterus; syncytiotrophoblast secretes enzymes that allow blastocyst to embed in uterine wall
What happens at day 8 post-fertilization?
blastocyst is partially embedded in endometrial stroma; trophoblast differentiates into 2 layers (cytotrophoblast and syncytiotrophoblast) and embryoblast differentiates into epiblast and hypoblast
The inner layer of the trophoblast; mononuclear cells; migrate into sync layer and fuse together to help it grow
Outer layer of the trophoblast; no distinct cell boundaries; multi-nucleated; produces human chorionic gonadotropin (HCG) which maintains hormone production by corpus luteum; pregnancy tests look for HCG
columnar cells of the embryoblast layer; adjacent to the cytotrophoblast
Cuboidal cells of the embryoblast layer; adjacent to teh blastocyst cavity
Subset of epiblasts that secrete fluid into the amniotic cavity
When and where does the amniotic cavity begin forming?
it's a small cleft in the epiblast leyr that begins forming on Day 8 post-fertilization
What happens on day 9 post-fertliziation?
- deeper embedment
- Sync forms many lacunae (holes)
- Flat cells form exocoelomic memebrane; surrounds the blastocyst cavity (which can now be called the primitive yolk sac); between this and the cytotrophoblast
- Bilaminar disc is columnar epiblast cells and cuboidal hypoblast cells
What happens on day 12 post-fertlization?
- Sync layer erods maternal capillaries and blood fills the lacunae (which is now called the trophoblastic lacunae)
- Blastocyst starts to protrude into uterus lumen
- Extraembryonic mesoderm proliferates to fill the space between exocoelomic memebrane and inner aspect of trophoblast; primitive yolk sac is filled with 2 layers of extraembryonic mesoderm; extra=in addition, surrounds and covers yolk sac and amniotic cavity
- Primitive yolk sac greatly increases in size
Outline the progression of the blastocyst cavity as it develops.
Blastocyst cavity-->exocoelomic cavity-->primitive yolk sac
What happens on day 13 post-fertliziation?
- Secondary yolk sac forms (entirely lined with extra-embryonic endoderm)
- Exocoelomic cyst forms (portions of exocoelomic cavity that are pinched off)
- Amniotic cavity (surrounded by amnion (inner fetal membrane)
- Primary villi form (cytotrophoblast cell columns surrounded by sync; finger like projections of the placenta; establish teh blood supply; form all the way around the chorionic plate though these will later by asymmetric; bleeding can occur at implantation site
What are the different implantation sites of the blastocyst?
- Abdominal cavity: typically in recto-uterine pounch; can sometimes have a viable pregnancy
- Ampullary region of the tube
- Tubal implantation: life-threatening; tube will rupture; surgical intervention is necessary but these make up 95% of ectopic pregnancies
- Interstitial implantation: narrow portion of the uterine tube
- Ovarian implantation
Do what benefits your patient
Do not harm patient
- the law of philosophy that addresses morals which are composed of rules (right and wrong) and values (good and bad)
- also includes methods which are composed of deontological (rule based reasoning, behave!) and teleological (values-based reasoning, be good!)
What is the difference between moral and methods in terms of the physician-patient relationship?
- As morals, ethics pertains to the ought or ought not of the physician-patient relationship
- As methods, ethics pertains to the discernment of what ought or ought not be done in particular situations and on what moral grounds
What are the 4 components of the physician-patient relationship?
- Professional relationship
- Voluntary relationship
- Socially binding contract
- Moral relationship
In terms of professional relationships, what must the physician makes sure happens?
- Benefits must flow to the patients, not the clinic ro the physician themself
- Don't violate public trust; sexual attraction happens, but don't act on it
In terms of voluntary relationship, when can a physician choose the patient?
- Physician may decline to accept individual as a patient but this varies with circumstances (AMA 9.06)
- Physician has an obligationi to share in providing care for the indigent
- Cannote decline patrietn based on race, color, religion, sexual orientation, etc. (AMA 9.12)
- Cannot decline patient in emergency situations (AMA 8.11)
- EMTALA governs how and whne patient may be refused or transferred to another hospital
What is the difference between termination and abandonment?
- Termination: not problematic; change in patient's insurance provider, phsyician illness, moving or retiring; cannot terminate without giving notice
- Abandonment: unilateral withdrawal by physician without first formally transferring care to another qualified physician acceptable to the patient; should never happen
What's the difference between a contract and a covenant?
- Contract: binding agreement between persons; enforced by law
- Covenant: relationship between eprsons, one of whom promises benefits or gifts while requiring certain behaviors of the beneficiaries; relationship can be either of these 2
Who is responsible for maintaining the morality of the physician-patient relationship?
The person with the most power (physician)
Definition: Health policy
A formal statement or procedure within institutions that defines priorities and the parameters for action
Where can you find health policies?
Public health, structural interventions, health care delviery/reimbursement, licensing of professionals, accreditation of healthcare providers and educational institutes
What are the major sources of health policies?
Internationl (WHO), government, professional organizations, accrediting organizations, and others (foundations, aid, etc.)
What the three things health policies are used for?
- Financing: Medicare, Medicaid, COBRA, SOBRA
- Reimbursement: state and local, public hospitals and clinics, health departments
- Licensure: boards for this; Kansas board of healing arts; accreditation of institutes
What are some recent reforms in healthcare in Kansas?
- exapansion of coverage by Medicaid (2002)
- creation of Kansas Health Policy Authority (2006)
- further expansion of coverage, prevention, and medical homes (2008)
What are some recent healthcare reforms seen at the federal level?
Patient protection and affordable care act (remember that reimbursement is policy)
What does intervention always necessitate?
Evaluation of said intervention
What is the ordering of health as regards health policies?
- Public health (clean water, etc.)
- Prevention (primary and secondary)
- Medical Care (tertiary prevention and interventions)
What are some barriers to effective communication with elderly persons?
- Ageism (discrimination; includes seeing age as a disease and not pursuing uncomfortable topics)
- Impaired hearing (not necessarily normal with age, but more frequent with age)
- Impaired vision
- Dysarthia (difficulty making speech sounds; common after stroke)
- Aphasia (inability to express oneself ins peech or understand other's speech)
- Altered mental status (can be baseline for patient; may not even realize they're sick)
When interviewing elderly patients, how do you take a comprehensive ROS?
- AGING GAMES
- Insomnia (less time in stages III and IV)
- Nutrition (5% in 1 month or 10% in 6 months)
- GI (constipation, diarrhea, etc.)
- GU (urine incontinence, UTIs)
- Assessment of function (ADLs and IADLs instruments of daily living)
- Mood and Memory
- Sexuality (erectile dysfunction and vaginal dryness)
When should you adress advance directives (such as wills and power of attorney) with an elderly patient?
Typically at the first visit
What is polypharmacy?
Taking more than 4 medications at one time
What is the best way to increase patient adherence with elderly patients?
Simplify, write instructions and encourage pill boxes
Absorption of radiant energy without enough energy for the radiolysis of water leads to the formation of what?
Hydroxyl free radicals: example of oxidative stress
Definition: Referfusion injury
- Damage to tissue caused when blood supply returns to the tissue after a period of ischemia (restriction in blood supply)
- The restoration of circulationi causes inflammation and oxidative damage through the induction of oxidative stress rather than normal functioning
When are patients with myocardial infarction at risk for reperfusion injury?
more than 20 minutes post-infarction; toxic O2 species are generated not during ischemia, but during reperfusion
Why is ischemic injury associated with inflammation?
because the production of cytokines and increased expression of adhesion molecules in certain cells
Parenchymal cells, enothelial cells, and infiltrating leukocytes all generate something that damages mitochondrial membranes and can lead to cell death. What is generated?
O2 free radicals
How do hydroxyl radicals cause cell death?
- They initiate lipid peroxidation and rip through the membrane
- Also damage proteins and enzymes
- Also induce single and double stranded breaks in DNA, cross-linking, and formation of adducts
How can hyroxyl radicals be produced?
Through the Fenton reaction
How can hydroxyl radicals be removed?
- SOD in mitochondria converts to H2O2 and then removes
- Glutathione peroxidase in mitochondria converts hydroxyl radicals to H2O2 and subsequently to water and oxygen
- Catalase converts H2O2 to water and oxygen as well
Individual, programmed cell death
What are some causes of apoptosis?
- Developmental morphogenesis (ie removing web-like fingers)
- Immune system regulation
- Viral infection (immune system tells cells to die)
- Cancers (some cancers bypass apoptosis, so not really a cause)
Which of the following is associated with an inflammatory response: apoptosis or necrosis?
What is a Councilman Body?
- A cell that is undergoing apoptosis
- A pink blob with no nucleus
Which of the following has more discrete DNA fragmentation: apoptosis or necrosis?
Fat, glycogen, lysosomes, iron, lipofuscin, melanin, exogenous pigments, hyaline are all examples of what?
Intracellular accumulations: things that look funny in the cell
What is the difference between dystrophic calcification and metastatic calcification?
- Dystrophic occurs in previously injured tissue only; can happen at normal serum levels; fat necrosis is an example
- Metatstatic occurs only at high serum calcium levels; can occur in any organ and in normal tissue; often related to bone metastases
What is the complete list of differences between apoptosis and necrosis?
- Apoptosis: programmed, physiological or pathological, tightly regulated, cell shrinks, condensation (membranes are intact), no inflammation, energy required, discrete DNA fragmentation, formation of blebs that phocytes come and remove which prevents inflammation
- Necrosis: exactly the opposite of all those points
Does apoptosis occur normally in adults?
Yes, regeneration of new cells and getting rid of cells that are old
What happens when the balance of death and proliferation is out of whack?
Cell attrition: too much cell death (Parkinson's, Sepsis, AIDS, myocardial infarction, type I diabetes)
Cell accumulation: too little cell death (cancer, SLE, Rheumatoid arthritis, polycythemia vera)
What is procaspase?
- inactive form of caspase
- contains a prodomain, large subunit, and small subunit
- if you remove one cysteine in active site, it will completely kill the activity of caspase
- can differentiate into intiator caspase and effector caspase
What does caspase do?
- Involved in apoptosis
- cysteine protease that cleaves protein substrates after an Asp residue
What is an initiator caspase?
- has a long prodomain; function is to cleave and activate effector caspases; binds to adaptor proteins that bring it in close proximity with effector caspase
- includes caspase 2, 8, 9, 10
What is an effector caspase?
- has short prodomains; do the bulk of breakdown in the cell; proeffector is cleaved by the initiator to make it active
- includes caspase 3, 6, and 7
What do Bcl-2 and Bcl-Xl have to do with apoptosis?
The inhibit it through the protection of the outer mitochondrial memebrane
What is the function of Bax and Bak?
They permeabilize the outer mitochondrial membrane to form a pore that allows cytC and Smac-DIABLO to leak out
What do BH-3 domain only proteins (ie BID, Noxa, BIM, BAD) do in regards to apoptosis?
they activate the multi-domain proteins (Bax and Bak) so that they'll form the pores
What do IAP proteins do?
- Inhibitor of apoptosis proteins (includes XIAP, cIAP1, and cIAP2)
- They suppress apoptosis by binding to and inhibiting both initiator and effector caspases
- in the cytoplasm, this is a way to prevent the unintentional activation of caspases
Where are caspases activated?
In the cytosol only
What is the function of Smac/DIABLO?
- It inhibits IAPS during apoptosis
- Inhibits the inhibitor
In a type I cell high activation of caspase 8 is enough to directly cleave and activate casp3. Which pathway does apoptosis take in this case?
Receptor mediated pathway
What are the steps of the receptor mediated pathway?
- death ligand (FAS, TNF, or TRAIL) binds to death receptor on outside of cell
- FADD binds to receptor on interior of cell
- FADD binds Casp8/10, cleaves, and activates it
- Casp8 goes directly to Casp3/7 and activates them
In a type II cell, there is low activation of casp8 and it is not sufficient to directlty cleave casp3. What pathway must be taken in this case?
Mitochondrial pathway to apoptosis
What are the steps of the mitochondrial pathway to apoptosis?
- Signal is presented to cell that says it's time to die
- BID is activated through cleavage (forms trunkated BID tBID)
- tBID activates Bax in the cytosol and Bak, which is loosely associated with the membrane
- Bax migrates to membrane where both Bax and Bak homooligomerize to form a pore in the membrane
- Intermembrane proteins cytC and Cma/DIABLO leak out to cytosol
- CytC interacts with Apaf-1 (wheel of death or apoposome); this recruits and activates casp9
- Casp9 activates casp3 (activates all others) and casp7
- Smac/DIABLO inhibits IAPs
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