FOM Week 6

Fluid filled cavity surrounding the embryo

Immature prescursor cell

embryo stage at which blastocele (cavity) forms in ICM (inner cell mass)

Cavity

cells of inner cell mass at blastocyst stage

Primary yolk sac

portion of the coelom that extends beyond the embryo body

the inner cells at the morula stage

the outer cells at the morula stage

cells of the outer cell mass at the blastocyst stage

Surrounds the amniotic cavity

has a small, indirect role in nutrition; becomes vascularized and nutrients are absorbed into blood for fetus

To help us understand normal development, embryological proceses recapitulated in adults, embryological components of diseases, and congenital malformations

• 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

sperm

• 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

• 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

2 cell stage is reached

4 cell stage is reached

• 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

• 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

deletion of zona pelluica, entry into uterine cavity

• 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

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

it's a small cleft in the epiblast leyr that begins forming on Day 8 post-fertilization

• 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

• 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

Blastocyst cavity-->exocoelomic cavity-->primitive yolk sac

• 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

• 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!)

• 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

• Professional relationship
• Voluntary relationship
• Socially binding contract
• Moral relationship

• 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

• 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

• 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

• 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

The person with the most power (physician)

A formal statement or procedure within institutions that defines priorities and the parameters for action

Public health, structural interventions, health care delviery/reimbursement, licensing of professionals, accreditation of healthcare providers and educational institutes

Internationl (WHO), government, professional organizations, accrediting organizations, and others (foundations, aid, etc.)

• 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

• exapansion of coverage by Medicaid (2002)
• creation of Kansas Health Policy Authority (2006)
• further expansion of coverage, prevention, and medical homes (2008)

Patient protection and affordable care act (remember that reimbursement is policy)

Evaluation of said intervention

• Public health (clean water, etc.)
• Prevention (primary and secondary)
• Medical Care (tertiary prevention and interventions)

• 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)

• AGING GAMES
• Audio/visual
• Gait/mobility/Falls
• 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
• Environment
• Sexuality (erectile dysfunction and vaginal dryness)

Typically at the first visit

Taking more than 4 medications at one time

Simplify, write instructions and encourage pill boxes

Hydroxyl free radicals: example of oxidative stress

• 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

more than 20 minutes post-infarction; toxic O2 species are generated not during ischemia, but during reperfusion

because the production of cytokines and increased expression of adhesion molecules in certain cells

O2 free radicals

• 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

Through the Fenton reaction

• 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

• Developmental morphogenesis (ie removing web-like fingers)
• Radiation
• Immune system regulation
• Viral infection (immune system tells cells to die)
• Cancers (some cancers bypass apoptosis, so not really a cause)
• Toxins

Necrosis

• A cell that is undergoing apoptosis
• A pink blob with no nucleus

Apoptosis

Intracellular accumulations: things that look funny in the cell

• 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

• 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

Yes, regeneration of new cells and getting rid of cells that are old

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)

• 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

• Involved in apoptosis
• cysteine protease that cleaves protein substrates after an Asp residue

• 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

• 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

The inhibit it through the protection of the outer mitochondrial memebrane

They permeabilize the outer mitochondrial membrane to form a pore that allows cytC and Smac-DIABLO to leak out

they activate the multi-domain proteins (Bax and Bak) so that they'll form the pores

• 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

In the cytosol only

• It inhibits IAPS during apoptosis
• Inhibits the inhibitor

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
• Apoptosis

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