Case 1 Flashcards
When does gastrulation begin?
3rd week of embryology
What triggers the start of gastrulation?
Formation of primitive streak and primitive node (cranial end)
What is gastrulation?
Formation of trigeminal gastrula - ectoderm, mesoderm, endoderm
What is does each trigeminal gastrulation layer form?
Surface Ectoderm- epidermis,hair, nails, lens of eyes
Mesoderm- muscle, bones, cartilage, adipose tissue, circulatory system
Endoderm- colon,stomach,bladder, pancreas
What is the prechordal plate?
Thickening of the hypoblast and epiblast; forms the mouth and helps to determine cephalic from caudal end
What is the notochord?
Layer of cells from primitive node that forms between the ectoderm and endoderm, and surrounded by mesoderm
It signals the formation of ectoderm neural plate
What does the notochord form?
Nucleus pulposus
When does neurulation begin?
Day 22
What happens during neurulation?
Neural plate forms > neural groove > neural folds elevate to fuse > neural tube
When does the anterior and posterior neuropores close?
Day 24/25 and 27/28
What are neural crest cells?
Cells from the neural folds that go on to make a range of body cells - PNS, adrenal medulla, and dentin of teeth
What are Somites?
Form from mesoderm along the length of neural tube from rostral to caudal end
Total of 44pairs
What do somites form?
Vertebrae, ribs, skeletal muscles, dermis, cartilage and tendons
What are the 3 primary vesicles?
Prosencephalon, Mesencephalon, Rhombencephalon
What are the three flexures?
Cephalic, Pontine and cephalic flexures
What are the secondary vesicles?
Prosencephalon - Telencephalon (cerebrum, basal ganglia and hippocampus) and Diencephalon (thalamus, uvea, retina)
Mesencephalon - mesencephalon (midbrain)
Rhombencephalon - Metencephalon (cerebellum + pons) and myelencephalon (medulla)
What is the development of the spinal cord?
Neural tube > neuroepithelial cells > neuroblast form mantle layer - grey matter > marginal cells form white matter cells
What divides the alar and basal plate?
Sulcus limitans
Where do the neural crest arise?
Dorsal neural tube along the whole length of spinal cord
How do neuronal migration in PNS occur?
Neuroepithelial cells express Snail1/2 > repress adhesion molecules > epithelial to mesenchymal transition > mesenchymal to destination and cease Snail1/2 expression
This is guided by somites
How is a Dorsoventral Axis developed?
TGF-beta (BMP) and SHH morphogens gradient
TGF - dorsal neural tube and SHH notochord and floor plate
The gradients activates Transcription factors that regulate differentiation of sensory and motor neurons
How is an Anterior-Posterior Axis Developed?
Retinoic acid from somites into anterior acid of neural tube (cephalic end)
FGF from stem zone cells into posterior axis of neural tube (caudal end)
Gradient of these two leads to different cell differentiation from the middle (anterior differentiate - posterior undifferentiated)
homeotic genes (HOX) express in clusters and the combination of genes determines the identity of block of tissue
Shh and FGF set up left and right hemisphere, brain and brain stem
What is neurogenesis?
Differentiation of progenitor cells into their programmed cells
How does the progenitor cell know which is apical and basal end?
Par complex at the tip of the cell
What are the two type of progenitor cell division?
Symmetrical = 2 daughter progenitor cells
Assymmetrical = 1 daughter progenitor and 1 neuronal cell
What does Shh do in neurogenesis?
It’s a mitogen for proliferation of progenitor cells
What does differentiated progenitor cells cleave to migrate?
Primary cilium
What is periventricular heterotropia?
Cluster of neurons forming in nodules that can’t be correctly placed formed from primary cilium not clearing properly
- leads to seizures, mild intellectual disabilities, brain malformation, microcephaly, delayed development
What is a neural tube defect?
Failure of neural tube closure
What is the epidemiology of NTD?
1.2 per 1000 births
anencephaly is 40%
SB 40%
What are the environmental factors linked with NTDs?
Diabetes
Lack of Folic Acid
What is the recommended intake of folic acid to prevent NTD?
Natural occurring Folinic Acid + THF
First occurrence= 400microgram daily before conception and 12wks during pregnancy
Recurrence= 4-5milligram per day
How do you diagnose NTD?
Increase in maternal serum alpha-fetoprotein (AFP) with amniocentesis during 16-18wks
[you can also measure acetylcholinesterase]
Ultrasonography for mother’s at risk To locate lemon sign
- anencephaly detected from 12wk
- SB detected from 16-20wks
What is a lemon/banana sign?
Ultrasound features of Arnold-Chiara Malformation in foetuses with open NTD
Lemon= scalloping of frontal bone Banana= caudal displacement changes cerebellum shape
What causes LEMON sign?
Low intracranial pressure due to downward shift of brain in SB causing frontal bone to flatten or scallop inward
Disappears with growth of foetus - frontal bone strengthens
Only present up to 24wks
What is the Arnold-Chiara Malformation?
Distortion of base of the skull with protrusion of lower brain stem and part of the cerebellum through foramen magnum
What are the four types of Arnold-Chiara Malformation?
Type 1: herniation of cerebellar tonsil and medulla through foramen Magnum
Type 2: herniation of cerebellar vermis, brain stem and fourth ventricle below foramen magnum (linked to myelomeningocele and hydrocephslus)
Type 3: herniation of entire posterior fossa contents and brain stem into a cervical encephalocele
Type 4: cerebellar hypoplasia
How is ACM treated?
Type 1&2 = posterior fossa decompression surgery to relieve pressure on spinal column and create space for cerebellum
What is a lumbar puncture?
It is drawing out of CSF from L4-L5 (use posterior iliac crest line)
First conduct CT to check there is no intracranial hypertension to prevent herniation
What is anencephaly?
Partial or complete absence of bone of rear skull, meninges, and cerebral hemispheres of the brain
What is cephalocele?
Herniation of cranial contents through skull defects
Cranial meningocele, encephalocele, ventriculocele
What is Holoprosencephaly?
Prosencephalon failing to divide into Telencephalon and Diencephalon due to SHH gene defect
What is Spina Bifida?
Lack of close of posterior neuropore
SB Occulta - open vertebrae arch with no external lesion
SB cystica - meningocele or myelomeningocele
Where does SB occulta occur mostly?
L5 and S1 w/ patch of hairy skin, dimple
What is myelomeningocele?
SB with spinal cord and nerve roots exposed in lesion causing paralysis of legs (higher lesion =more severe)
Lumbrosacral in 80% and 90% complicated by hydrocephalus
What is meningocele?
Protrusion of méninges without neural tissues
5% of SB
What is hydrocephalus?
Accumulation of CSF in the intracranial cavity caused by excess CSF prod, decrease reabsorption via arachnoid granulations and obstruction of flow in ventricle system
What are the symptoms of Hydracephalus?
Headache, nausea, vomiting, cognitive impairment, decreased vision, CN VI palsy (can’t abduct properly) and anterior fontanelle bulge
Treatment = ventriculostomy, ventriculoperitoneal shunt
What is Bipolar Disorder?
Mental illness characterised by periods of elevated mood (mania) and depression
What are the two types of Bipolar Disorder?
Type I: mania alternating with depressive episodes
Type II: one hypomania period and one major depressive episode in a lifetime (depression period is predominant and can be mistaken for MDD)
What is the Epidemiology of Bipolar Disorder?
- 2.4% life time prevalence
- 1.1:1 ratio M:F
- Any age onset (BD1 = 18; BD2= mid-20s)
- life expectancy = reduced by 9-20yrs
- suicide risk 15x bigger than population (10-15% die by suicide)
- comorbid disorders: anxiety disorder in 75%; ADHD; drug and alcohol misuse in 60%
What are the symptoms of Mania?
Last at least 1wk
3 or more: inflated self esteem, decreased need for sleep, pressure of speech, racing thoughts, distractibility, goal-directed and high risk/painful consequence activity
Cause impairment in social or occupational function and may need hospitalisation
What is Hypomania?
Last at least 4 consecutive days
3 or more of: inflates self-esteem, highly irritable, distractibility, decrease need for sleep, pressure of speech, racing thoughts, increase goal-directed and high pain/risk consequence activities
Doesn’t cause impairment in social or occupational functioning or need to hospitalise
Improve productivity
What is the Aetiology of Bipolar Disorder?
Genetics: 70% heriditability; genes involved in calcium and sodium voltage channels, NMDA receptors, insulin secretion regulation [Type I linked with SCHZ and II
with MDD]
Environmental: stress and loss, medications (corticosteroids, L-Dopa, thyroid hormones, MAO-I/TCAs, antidepressants - lead to Mania), substance misuse, AIDs, Epilepsy, Head injury, MS, hypothyroidism, CVD,
What is the link between Bipolar and Dopamine?
Increase DA synthesis in striatum (all subdivisions) leading to psychotic symptoms
How are the different phases of Bipolar Disorder treated?
Acute Mania: antipsychotics - olanzapine, risperidone, quetiapine; antiepileptic- Valproate and Carbomazepine; mood stabiliser - Lithium
Acute MD phase: don’t give antidepressants; antiepileptic- Lamotrigine; antipsychotic - quentiapine (low dose); Lithium
Maintenance Phase: prophylaxis - Lithium, Olanzapine and Valproic Acid (prevents mania)
Why are other antipsychotics not good for maintenance?
Because they only protect against mania
What is the mechanism of Lithium?
Administered in a salt (carbonate or citrate)
It’s mechanism is not completely understood
Rapidly absorbed by the upper GIT and 95% is excreted by kidney
It increase serotonin and GABA neurotransmission and decrease Glutamate and Dopamine
What are side effects of Lithium
Fine tremor (give propranolol - Beta Blocker), Weight gain, nephrogenic diabetes insipidus(NDI)
Long-term leads to hypothyroidism and Kidney problems (especially in women under 60y and people with high lithium blood conc.)
What is the MOA of Valproate?
Increases GABA neurotransmission - depress Sodium voltage gated channels, inhibits GABA transaminase, and glutamate formyl transferase
Side effects of Valproate?
Nausea, tremor, weight gain, folate antagonist - increasing likelihood of NTDs
How do antipsychotics work?
Block D2 receptors and serotonin receptors reducing over activity of Mesolimbic and mesocortical pathways
What are the NS cells
CNS:
Ependymal - line ventricles and central canal; secrete, circulate and monitor CSF
Microglia- remove debris (phagocytosis)
Astrocytes- BBB, structural support, absorb and recycle neurotransmitters, form scar tissues after injury
Olingocytes- myelinate CNS neurones
Schwann cells- myelinate PNS neurones
Satellite cells- surround neurone cell bodies in ganglia; regulate nutrient and neurotransmitter leaves around neurones in ganglia
What is the Abortion Act 1967?
2 practitioners can agree to terminate pregnancy if:
- doesn’t exceed 24wks and continuation causes risk to mother or family
- termination prevents risk to mother
- termination prevents risk to child
- after 24wks IG prevents harm to mother or child being seriously handicapped
What is the different level of consent?
Under 16: Gillick competent
16-17: family Act 1969
