FHMP Tutorials

Genetics – Hassan
Details already outlined in last year’s tutorials

Embryology –Yusuf
Order: gametogenesis, fertilisation, cleavage, compaction, implantation, gastrulation,
organogenesis
Gametogenesis –
oogenesis
 Before puberty – prophase 1
 After puberty – metaphase 2
 Fertilisation – continuation of meiosis
Spermatogenesis
 Meiosis starts after puberty
Fertilisation –
 binding of zp3 to sperm
 induces release of enzymes to break down zona pellucida
 fusion of plasma membrane and sperm causes ca release in egg
 continuation of meiosis + cortical reaction
 modify zp3 to prevent polyspermy
 polyspermy and hyditaform moles
Cleavage –
 fertilised egg divides but no growth of cells
 each cell in a blastula = blastomere
 morula = 16 cells
 cells in the cleavage stage appear to repel
 twins: 30% in monozygotic twin’s cleavage division =>
 70% of monozygotic twins when ICM divide
 conjoined twins
 tetra gametic chimera
Compaction –
 starts after morula
 cells start to adhere
 can identify cells in contact with zona pellucida and cells in the centre
 forms blastocyst with trophoblast, inner cell mass and blastocoel
Implantations –
 ampulla of the fallopian tube
 blastocyst attaches to uterus
 embryo hatches from ZP
 Trophoblast attaches to endometrium and starts rapid proliferation
 Syncytiotrophoblast produced that penetrates uterine wall via enzyme action
digesting ECM between cells of endometrium
 Syncytiotrophoblast invades and reaches maternal capillaries
 Ectopic pregnancy
 ICM -> hypoblast + epiblast
  Hypoblast = Heuser’s membrane
Gastrulation –
 primitive streak appears
 cells from epiblast ingress to form embryonic endoderm by pushing hypoblast
 second wave ingress between endoderm and epiblast to form mesoderm
 cells engrossing through the node form the notochord
 notochord replaced by axial skeleton but remnants in nucleus pulposus between
intervertebral discs
 Endoderm forms…. + ectoderm forms….
 Mesoderm -> intermediate… + lateral plate (splanchnic and somatic) + Paraxial
(Sclerotome (SHH) = axial skeleton) + (Myotome (SHH+BMP) =skeletal muscle) +
(Dermatome (WNT) = dermal layer of skin)
Neurulation –
 Notochord induces ectoderm rostral to notochord to develop into neural plate
 Regression – neural plate expands but primitive doesn’t
 Notochord signals neural plate folding
 Neural crest cells pinched off
 Neural tube = cns
 Neural crest cells = pns
 Neural tube defects = anencephaly and spina bifida, can be
prevented by folic acid
Embryonic induction + morphogens and patterns

Haematology – Ifrah
(same outline as last year – edits will be discussed between myself and Ifrah)
- Difference between FFP and cryoprecipitate and why they are kept at given condi5ons.
- ABO blood group and co-dominance.
- RhD an5gen and haemoly5c disease of the newborn.
- An5-globulin tests
- Erythropoiesis → mainly understand difference between re5culocyte and erythrocyte.
- Haema5nics i.e. stem cell factor, B12, folate, iron etc.
- Microcy5c, normocy5c and macrocy5c anaemia.
- MAIN FOCUS ON COAGULATION CASCADE
- Platelet aggrega5on → vW factor etc
- Importance of vitamin K and deficiency, factors 2, 7, 9 and 10 as well as protein C and S.
- Heparin/warfarin
- Fibrinolysis
- PT, APTT, TT.

Pharmacology – Khadija
1. Dose – binding affinity varies
2. Chemical Specificity – binding is specific to compound
3. Biological Specificity – binding is specific to macromolecule
Ligand-gated ion channels: multimer 3-5 subunits
fast neurotransmission (binding of neurotransmitter = pore opens)
 Cell depolarises = Vm less negative = excitation
 Cell hyperpolarises = Vm more negative = inhibition
 E.g. Nicotinic superfamily (nicotinic receptors to ACh, GABA receptors) Glutamate
superfamily, Purinergic superfamily (ATP)
 Other ion channels which aren’t receptors but drug targets:
 Voltage-gated channels (sodium channels, calcium channels, potassium channels)
 Local anaesthetics, calcium channel blockers, antiarrhythmic drugs
 TRP channels are similar to potassium channels but can sense ligands (capsaicin in
peppers!), and changes in temperature and voltage
G-protein coupled Receptors: 7 Transmembrane proteins + trimeric G-protein
Slow neurotransmission (metabotropic receptor)
 Trimeric g-protein = alpha subunit and beta gamma subunit
 GDP is bound to alpha subunit in resting state
 When agonist binds to receptor, receptor binds to the alpha subunit causing GDP exchange
for GTP
 The alpha and the beta gamma subunits dissociate
 Alpha and beta gamma reach and activate or inhibit effectors
 GTP hydrolyses, trimer forms again
 Effects mostly due to second messengers
o cAMP – this is synthetized from ATP by adenyl cyclase and activates intracellular
kinases which phosphorylate other proteins
 b adrenoceptors = activate adenyl cyclase =  cAMP
 a2 adrenoceptors + opioid receptors = inhibit adenyl cyclase = cAMP
o PLC/Calcium – a1 activates PLC = hydrolyse membrane phosphatidylinositol = 2
second messengers IP3 (release Ca) + DAG (activates protein kinase C)
o Direct effects
Catalytic/ Kinase linked receptors:
Nuclear receptors = ligand-ligand activated transcription factors
 steroid receptors (when inactive they are in the cytoplasm, bound to proteins such as heat-
shock proteins)
 PPAR etc (sense lipids generally already normally present e.g. fatty acids, reside mostly in
the nucleus).
EC50 = potency, maximum response = efficacy
Glycine = high affinity = full agonist, Taurine = low affinity = partial agonist
Positive modulators increase effects of agonists