Case 1 Flashcards
What is validity? and what are the two types?
Validity is the extent to which a variable or intervention measures, or accomplishes what it is supposed to accomplish.
Two types of validity should be considered in every study:
a) The internal validity of a study refers to the integrity of the experimental design – was the experimental design appropriate? Internal validity is threatened by biases, i.e. a study that is sufficiently free from bias is said to have internal validity
b) The external validity of a study refers to the appropriateness by which it results can be applied to non-study patients or populations
What’s a confounding variable?
An extra variable, which is associated with the exposure and also influences (confounds) the disease outcome – i.e. it is not the variable the researchers are interested in, but it may potentially affect the results of a study/trial
What’s gastrulation?
- Formation of 3 germ layers – endoderm, mesoderm, ectoderm
- Between 14-16 days post-fertilisation
Describe placental development. How does it develop and why is it important?
- Placenta develops from outer layer of cells of blastocyst (trophectoderm)
- Development precedes embryonic development
- Placenta is critical for the establishment of pregnancy and survival of embryo
- Placental growth is very rapid in early pregnancy, slower in later pregnancy
- Placenta forms a protective barrier around the blastocyst
- Placenta mediates implantation
- Produces hormones that establish pregnancy
- Provides nutrition to embryo
- Protection from teratogens
Describe placental growth throughout the 3 trimesters.
1st trimester - Rapid placental growth 2nd trimester - Placental regression = produces disc shaped placenta - Forms placental membrane 3rd trimester - Rapid fetal growth - 250g/wk - Placental growth slows - Increased placental efficiency
Describe the tissues of the human blastocyst? and when is it formed? and what do the cells give rise to?
- Human embryo – blastocyst – 32-64 cells
- 4-5 days post-fertilisation
- ICM (inner cell mass) – pluripotent stem cells here – gives rise to embryo and every cell in our bodies now
- Trophoblast – contains trophoblast stem cells – gives rise to embryonic component of placenta and extraembryonic tissues
When does implantation take place, and what happens?
- Occurs around day 8 post-fertilisation
- Blastocyst becomes embedded in uterus; secretes enzymes to digest uterine endometrium
- Endometrium closes, development continues in uterine wall
- Trophoblast cells contribute to formation of placenta
What are the extraembryonic membranes?
- Amnion – entirely surrounds embryo, makes cavity filled with amniotic fluid
- Chorion – becomes principle part of placenta
- Allantois – becomes vascular connection between embryo and placenta – umbilical cord forms from this
What is the yolk sac?
The first site of blood cell formation.
Why is gastrulation important?
- Organs derive from specific germ layers
- Gastrulation allows cell movements to get tissues and organs in correct orientation
- Germ layers give rise to different tissues
- Must generate all tissue and cell types of body
Describe the initiation of gastrulation?
- An invagination of cells within the caudal half of the epiblast - the primitive streak
- Day 15 – embryo developing as a flattened disk – cells begin to progress through the primitive streak and the embryo begins to change shape
Describe the three layers formed during gastrulation?
Ectoderm: outermost of the three tissue layers in the embryo of a metazoan animal, which will produce the epidermis and nervous system of the adult
Mesoderm: one of the three tissue layers in the embryo of a metazoan animal, which will produce many internal organs of the adult such as the muscles, spine and circulatory system
Endoderm: one of the three tissue layers in the embryo of a metazoan animal, which will produce the digestive system and other internal organs of the adult
What’s the neural plate?
A thick, flat bundle of ectoderm formed in vertebrate embryos after induction by the notochord
Describe organogenesis in terms of the ectoderm.
- The process of differentiation is regulated by cellular signalling cascades
- One of the primary steps during organogenesis is the formation of the neural system
- The ectoderm forms epithelial cells and tissues, as well as neuronal tissues
- During the formation of the neural system, special signalling molecules called growth factors signal some cells at the edge of the ectoderm to become epidermis cells
- The remaining cells in the centre form the neural plate
- If the signalling by growth factors were disrupted, then the entire ectoderm would differentiate into neural tissue
- The neural plate undergoes a series of cell movements where it rolls up and form the neural tube
- In further development, the neural tube will give rise to the brain and the spinal cord
Describe organogenesis in terms of the mesoderm.
- The mesoderm that lies on either side of the vertebrate neural tube will develop into the various connective tissues
- A spatial pattern of gene expression reorganises the mesoderm into groups of cells called somites, with spaces between them
- The somites will further develop into the ribs, lungs, and segmental (spine) muscles
- The mesoderm also forms a structure called the notochord, which is rod-shaped and forms the central axis of the body
Describe organogenesis in terms of the endoderm.
- The endoderm consists, at first, of flattened cells, which subsequently become columnar
- It forms the epithelial lining of the whole of the digestive tube (except part of the mouth and pharynx) and the terminal part of the rectum
- It also forms the lining cells of all the glands which open into the digestive tube, including those of the liver and pancreas; the epithelium of the auditory tube and tympanic cavity; the trachea, bronchi and air cells of the lungs; the urinary bladder and part of the urethra; and the follicle lining of the thyroid gland and thymus
- Additionally, the endoderm forms internal organs including the stomach, the colon, the liver, the pancreas, the urinary bladder, the epithelial parts of the trachea, the lungs, the pharynx, the thyroid, the parathyroid, and the intestines
Describe the development of the cardiovascular system.
- Begins around 22-23 days post-fertilisation
- Visible on ventral surface
- Continues through week 8
- Heart beat begins day 22, circulation begins day 27-28
- First organ to function in embryo
- Required for embryonic and foetal growth
- Formation of blood and blood vessels begins in the mesodermal wall of the yolk sac as well as in the wall of the chorion outside the embryo proper
- By the beginning of the 5th week cardiogenesis is well underway and the embryonic circulation is functional – the liver takes over the role of haematopoiesis
- Structures designed to facilitate separate systemic and pulmonary circulations form between 5th and 8th weeks of gestation, although a dual pump is not operational until immediately after birth
Describe the development of the nervous system.
- Apparent after gastrulation
- 19-21 days post-fertilisation
- Neural tissue forms from ectoderm
- Cephalic region – neural plate – gives rise to brain
- Neural tube - along dorsal region – gives rise to spinal cord
Describe the neural tube closure. What are the issues related to this?
- The neural plate rolls up to form the neural tube with neural crest cells forming at the boundary with the ectoderm
- Folding of neural ectoderm to form tube
- 23-26 days post-fertilisation
- Important for development of spinal cord and brain
- Neural tube defects – failure to close
- exencephaly – fails to close in brain region
- spina bifida – fails to close in spinal region
Describe the neural crest formation.
- Cells that migrate out of dorsal neural tube
- Incorporated in variety of tissues
- These cells become:
- neurones and glia of ANS
- glial schwann cells of PNS
- melanocytes of skin
- bone, cartilage, muscle, connective tissue of face
Describe the development of the GI system.
- Initially arises from endoderm week 2/3
- Contributions from other germ layers week 4 onwards
- mesoderm – mesentery, smooth muscle, blood vessels
- ectoderm – enteric nervous system
- Foregut – oral cavity, oesophagus, trachea, stomach
- Midgut – small intestine and pancreas (intestines herniated during development and rotate to acquire adult morphology)
- Hindgut – colon
Describe the development of the renal tract.
- Develops in close association with genitals
- Urogenital ridge
- Development in 3 stages – pronephros (day 18), mesonephros (day 24), metanephros (day 35)
- Branching morphogenesis
When’s the first ultrasound scan during pregnancy and what’s it for?
First ultrasound – 12 weeks
- To check if the pregnancy is in the right place – location – (ectopic?)
- To check if the pregnancy is viable – right size and heartbeat
- To check for the number of foetuses
- To give an indication of the date of pregnancy
- To check for any defects in the cardiovascular system – mainly defects with the heart
- Baby is fully formed at this point
- Sonographer estimates when baby is due
When’s the second ultrasound scan and what’s it for?
Second ultrasound – 20 weeks
- To check for any structural defects
- To check if the ventral wall has closed properly
- Usually find out gender
When is a pregnancy described as viable?
From when heart pulsations can be visualised within gestation sac
What are the two ways of doing an ultrasound during pregnancy? and which is better?
- Transabdominal and transvaginal – transvaginal ultrasounds are more useful because the probe is closer to the uterus and so provides a better image, especially with increasing concerns regarding obesity, it’s better to image the uterus close up
What is the earliest indication of pregnancy but not a diagnosis?
A thickened endometrium
What are ultrasounds also used for during pregnancy?
For screening (along with blood tests) - but it gives a risk not an answer
Explain the usage of modern hormone assay techniques (ELISA) as pregnancy tests
- Used to diagnose pregnancies
- Pregnancy tests detect betahCG (a glycoprotein that is secreted by the placenta shortly after fertilisation) in the urine
- It starts to be produced around 6 days after fertilisation
- betahCG is in the blood and should double in 48 hours
- test works by binding the hCG hormone, from either blood or urine, to an antibody and an indicator – the usual indicator is a pigment molecule, present in a line across a home pregnancy urine test
Explain what happens during the ELISA test.
- urine applied to exposed end of strip
- antibodies on first strip bind to hCG
- dye activating enzymes attached to antibody
- another antibody attached to hCG causing molecule to stick and allowing enzymes to cause change in colour
How reliable is the ELISA test?
- now very sensitive
- a positive test result is almost certainly correct
- however, a negative test result is less reliable – the result may not be reliable if you don’t follow the instructions properly or take the test too early
What is the placenta for?
- Mediates relationship between mother and baby
- Entirely responsible for nourishing and supplying oxygen to the fetus
- Fetal suppy line – acts as lungs/GI tract/kidney/liver
- Growth and survival of fetus absolutely dependent on healthy, optimally functioning placenta
What are the 3 main functions of the placenta? Give more detail.
- Nutrient and gas exchange
- Hormone production and secretion
- Protective barrier
- Placenta forms a protective barrier around the blastocyst
- Placenta mediates implantation
- Produces hormones that establish pregnancy
- Provides nutrition to embryo
- Protection from teratogens
How is the structure of the placenta appropriate for its function?
- Large surface area – exchange
- Highly vascularised
What is the syncytiotrophoblast?
- Outer layer of villi – multinucleated, continuous, thin
- Highly specialised cell type for nutrient and gas exchange, hormone production
What are the mechanisms of transfer in the placenta?
- The placenta is not just a sieve
- Tight regulation of transfer across syncytiotrophoblast
1. Diffusion
2. Facilitated diffusion
3. Endocytosis/exocytosis
4. Active transport
Lipophilic substances – transcellular diffusion
Hydrophilic substances, e.g. sugars, small molecules, metabolites – paracellular diffusion
Which hormones does the syncytiotrophoblast produce?
- hCG
- placental lactogen
- placental growth hormone
- progesterone
- oestrogen
Why is hCG important in the maintenance of pregnancy?
- prevents regression of corpus luteum
- essential for establishment of pregnancy
Why is hCG a marker of a normal placenta? How do levels of this hormone change, and what can unusual levels also suggest?
- detectable in blood 24-48 hours after implantation
- doubling every 48 hours
- low levels in failing pregnancies (miscarriage)
- high levels in Down’s syndrome
- peaks at around 8 weeks gestation
- linked to morning sickness
What steroid hormones that the placenta produces are important during pregnancy and why?
Progesterone
- primes endometrium for pregnancy
- inhibits myometrial contractility
- blockade of progesterone (e.g. mifepristone) used to induce abortion
- strengthens the cervical mucus plug to prevent infection
- stimulates the growth of breast tissue
Oestrogen
- increase uterine blood flow
- stimulates the growth of breast tissue & myometrium (uterus)
What is used to induce abortion?
Blockade of progesterone, e.g. Mifepristone
