PBL Topic 3 Case 1 Flashcards
What is gastrulation?
- The process that establishes all three germ layers in the embryo
Identify the three germ layers in the embryo and what they form.
- Ectoderm: nervous system
- Mesoderm, cardiovascular system, renal system, spleen
- Endoderm, GI tract and epithelia of respiratory systme
Where is the primitive streak located and when is it visible?
- Surface of the epiblast
- Day 15/16
What is invagination?
- Epiblast cells move towards primitive streak
- They become flask-shaped, detached from the epiblast
- They slip beneath the epiblast
Describe the molecular regulation of gastrulation.
- Fibroblast Growth Factor 8
- Which down-regulates E-cadherin between epiblast cells
Which cranial nerves does the ectodermal germ layer give rise to?
- Vagus nerve (10)
- Glossopharyngeal (9)
- Vestibulocochlear (7)
- Trigeminal (5)
- 1975
Describe the molecular regulation of neural plate formation.
- Fibroblast Growth Factor
- Which upregulates chordin and noggin
- Which inhibits Bone Morphogenetic Protein
- Which allows ectoderm to become neural tissue
Describe the process of neurulation.
- Lateral edges of neural plate become elevated to form neural folds
- Depressed mid-region forms the neural groove
- Neural folds approach each other in the midline
What is the function of neuropores during neurulation?
- Allow neural tube to communicate with amniotic cavity until neurulation is complete
On which days do the anterior and posterior neuropores close?
- Anterior: day 25
- Posterior: day 28
Identify the transition that neural crest cells undergo
- Epithelial to mesenchymal
- Mesenchyme refers to embryonic connective tissue regardless of origin
Identify the two pathways of neural crest cells.
- Dorsal pathway: to form melanocytes and hair follicles
- Ventral pathway: neurons, Schwann cells and cells of the adrenal medulal
Describe the molecular regulation of neural crest cells.
- Intermediate levels of BMP
- Which induce transcription factors
- PAX3, SNAIL, FOXD3 are responsible for specification
- SLUG which promotes migration
Identify the embryological origin of the structures of hearing and equilibrium
- Otic placodes
Identify the embryological origin of the structures sight
- Lens placodes
Name the three primary brain vesicles and what they refer to.
- Prosencephalon - forebrain
- Mesencephalon -midbrain
- Rhombencephalon - hindbrain
Where is the cervical flexure located?
- At the junction between the hindbrain and spinal cord
Where is the cephalic flexure located?
- In the midbrain region
Identify the two portions of the prosencephalon
- Telencephalon
- Diencephalon
Identify the two portions of the rhombencephalon and how are these two structures separated?
- Metencephalon
- Myelencephalon
- Pontine flexure
Identify the ventricles of the brain
- Cerebral hemispheres are lateral ventricles
- Diencephalon is third ventricle
- Rhombencephalon is fourth ventricle
How are the third and fourth ventricles connected?
- Cerebral aqueduct
How are the lateral ventricles connected to the third ventricle?
- Interventricular foramina of Monroe
Where are neuroepithelial cells located?
- The walls of the recently closed neural tube
Neuroepithelial cells differentiate into what type of cell?
- Neuroblasts which form the mantle layer
What does the mantle layer form?
- Grey matter
What does the marginal layer form?
- White matter
- Which appears white due to myelination
How are basal and alar plates formed and what do they form?
- Thickening of mantle layer due to addition of neuroblasts to form ventral (basal) and dorsal (alar) thickenings
- Basal plate forms motor areas of spinal cord
- Alar plate forms sensory areas
What is the name of the longitudinal groove that separates the basal and alar plates?
- Sulcus limitans
In which region is the intermediate horn located?
- T1-L3
Describe the molecular regulation of nerve differentiation in the spinal cord.
- Ventral motor neuron differentiation is dependent on low TGF-B and high SHH
- Dorsal sensory neuron differentiation is dependent on high TGF-B and low SHH
Outline the epidemiology of spina bifida
- 2/ 1000 births affected
- M:F ratio of 2:3
Describe the pathology of spina bifida occulta.
- Vertebral arches are not covered by skin
- Does not involve underlying neural tissue
- Marked by tuft of hair in affected region (typically S1-S2
Describe the three types of Spina Bifida Cystica
- Meningocele, in which fluid-filled meninges protrude through the defect
- Myelomeningocele, in which neural tissue is included in the sac
- Myeloschisis, in which neural tube does not elevate but remains flattened
What is an Arnold-Chiari malformation?
- Herniation of part of the cerebellum into the foramen magnum
- Due to spinal cord being tethered to vertebral column
- Which pulls the cerebellum into the foramen magnum
Identify three causes of neural tube defects.
- Hyperthermia
- Valproic acid
- Hypervitaminosis A
What reduces the occurance of NTDs?
- Folic acid (folate)
- Which is responsible production, repair and functioning of DNA
How does the risk of NTDs increase if folic acid is not taken?
- Risk if one sibling has condition= 4%
- Risk if two siblings have condition = 10%
Where is cerebrospinal fluid secreted from?
- Choroid plexuses of the brain ventricles
Outline the pathway taken by CSF from the choroid plexus to the venous system
- Leaves lateral ventricles through interventricular foramina of Monroe
- Enters the third ventricle
- Passes through cerebral aqueduct into fourth ventricle
- Either enters spinal canal or passes into subarachnoid space through medial and lateral apertures
- Passes arachnoid granulations into the superior sagittal sinus.
What is the role of CSF?
- ‘Floats’ the brain, providing cushioning
- Gives its buoyancy so that it does not compress the cranial nerves
Outline the pathology of exencephaly
- Failure of cephalic part of neural tube to close
- Skull does not form so brain is exposed
- Leading to necrotic tissue (anencephaly)
Which cranial nerves arise from the brain stem?
- Olfactory (1)
- Optic (2)
Which cranial nerve arises from outside the hindbrain?
- Oculomotor (3)
Which cranial nerves arise from the rhombomeres of the hindbrain?
- Trochlea (4)
- Trigeminal (5)
- Abducens (6)
- Facial (7)
- Vestibulocochlear (8)
- Glossopharyngeal (9)
- Vagus (10)
- Accessory (11)
- Hypoglossal (12)
What is bipolar disorder?
- Episodes of depression and hypomania (mania if severe)
How is one cycle of bipolar disorder defined?
- From euthymic to manic, to depressed and returns to euthymic
What is the difference between bipolar 1 and bipolar 2?
- Bipolar 1: one or more manic or mixed episodes
- Bipolar 2: depressive episodes which are more frequent than manic episodes, with a history of at least one hypomanic episode
How heritable is bipolar disorder?
- Very heritable (80%)
What is meant by cyclothymia?
- Personality trait with spontaneous mood swings not sufficient or persistent enough to warrant anther diagnosis
Identify 6 clinical features of mania
- Elevated and irritable
- Flight of Ideas
- Grandiose and self-confident
- Delusions of wealth, power and influence
- Disinhibition with increased sexual activity, excessive drinking and spending
- Insomnia
Identify 6 clinical features of depression
- Depressed and irritable
- Slow, monotonous speech
- Feelings of guilt, worrying, suicidal thoughts
- Weight gain / loss
- Loss of libido / erectile dysfunction
- Reduced energy lacking motivation
Outline the mechanism of action of lithium
- Inhibition of inositol monophosphatase blocking PI pathway
- Inhibition of glycogen synthase kinase
Identify three adverse effects of short-term lithium use.
- Nausea
- Vomiting
- Tremor
Identify three adverse effects of long-term lithium use
- Hypothyroidism
- Nephrogenic diabetes insipidus
- Renal failure
- Patients therefore receive screening of thyroid and renal function prior to starting lithium
Why is lithium not advised during pregnancy?
- Lead to Ebstein’s anomaly, a foetal malformation that affects the tricuspid valve
Identify three antiepileptic drugs that are used in the treatment of bipolar disorder.
- Sodium valproate
- Carbamazepine
- Lamotrigine
Outline the mechanism of action of antiepileptic drugs
- Block of sodium channels
- Enhancing GABA-mediated synaptic inhibition
- Inhibiting T-type calcium channels
Which antiepileptic drug are most effective in treating acute attacks of mania?
- Valproate
- Carbamazepine
Which antiepileptic is most effective in preventing the recurrence of both mania and depression?
- Lamotrigine
Explain how valproate causes spina bifida.
- Folate antagonist
- It inhibits dihydrofolate reductase, an enzyme used to activate folic acid
- Which is essential for production, functioning and repair of DNA
Identify four side effects of lamotrigine
- Nausea
- Dizziness
- Ataxia
- Hypersensitivity
Identify a side effect of valproate
- Thinning and curling of hair
Identify an antipsychotic drug used to treat bipolar disorder.
Describe its mechanism of action
- Olanzapine (given in combination with antidepressant fluoxetine)
- D2 and 5-HT antagonist properties
How are neural tube defects diagnosed?
- Ultrasound
What is the banana sign?
- Way in which cerebellum wraps around brain due to spinal cord tethering
- Resulting in destruction of cisterna magna
- Cerebellum takes shape of a banana
What is the lemon sign?
- Indentation of frontal lobe
- Due to decreased pressure as a result of closure of posterior neuropore
How can maternal serum be used to diagnose neural tube defects?
- AFP levels in amniotic fluid and maternal serum are elevated
What is meant by a Chiari malformation?
- Congenital defect causing caudal displacement of cerebellum and brainstem
What is a Chiari 1 malformation?
- Most common
- Caudal descent of cerebellar tonsils
- Remains asymptomatic until adulthood, presenting as headache
- Associated with hydrocephalus
What is a Chiari 2 malformation?
- Caudal descent of cerebellar tonsils and brainstem
- Presents as lemon sign, banana sign
- Associated with myelomeningocele
What is a Chiari 3 malformation?
- Rare anomoly
- Low occipital and high cervical encephalocele with herniation of posterior fossa contents
What is a Chiari 4 malformation?
- Extreme form of cerebellar hyperplasia
How are Chiari 1 and 2 malformations treated?
- Posterior fossa decompression surgery to relieve pressure
- Ventriculoperitoneal shunt to drain CSF
- Management of neurogenic bladder
What is hydrocephalus?
- Abnormal accumulation of CSF within the ventricular system
- Resulting in ventriculomegaly
What is communicating hydrocephalus and what causes it?
- CSF is able to leave ventricles but there is obstruction in subarachnoid space / arachnoid granulations
- Causes include SAH in adults
What is an obstructive hydrocephalus and what causes it?
- CSF is unable to leave ventricles due to aqueductal stenosis in newborns or gliomas/cysts in adults
What is the treatment for communicating hydrocephalus
- Ventriculoperitoneal shunt
What is the treatment for obstructive hydrocephalus
- Ventriculostomy
Where are homeobox genes expressed?
- Notochord
- Prechordal plate
- Neural plate
How many segments is the hindbrain composed of? What name is given to these segments?
- Eight
- Rhombomeres
What is the role of HOX genes?
- Specification of forebrain and midbrain
- Causes cranial rhombomeres to differentiate into more caudal types
How are HOX genes regulated?
- Retinoids
- Where excess retinoic acid shifts HOX gene expression anteriorly
What causes a small hindbrain?
- Retinoic acid deficiency
Where are LIM1 and OTX2 expressed and what is their role?
- LIM1: Prechordal plate
- OTX2: Neural plate
- Specification of forebrain and midbrain
How is LIM1 and OTX2 production induced?
- By anterior neural ridge and rhombencephalic isthmus
- Which secrete FGF8
What is holoprosencephaly?
- Loss of midline structures of brain and face
Outline 1 severe and 1 mild clinical feature of holoprosencpahly
- Severe: Lateral ventricles fuse into a single telencephalic vesicle
- Mild: Single incisor tooth
Outline the pathophysiology of holoprosencephaly
- Abnormalities in 7-dehydrocholesterol reductase (Smith-Lemli-Opitz syndrome)
- Reduced cholesterol results in abnormal SHH signalling
- SHH is responsible for establishing ventral midline in the CNS
What is Schizencephaly
- Condition in which large clefts occur in the cerebral hemipsheres
Outline the pathophysiology of Schizencephaly
- Mutation in EMX2
- Ossification defects in squamous part of occipital bone
Outline 3 types of schizencephaly
- Meningocele: Meninges bulge through opening of occipital bone
- Meningoencephalocele: Brain bulges through opening of occipital bone
- Meningohydroencephalocele: Ventricle bulges through opening of occipital bone
In which region do neural folds meet each other initially?
- Fifth somite (cervical region)
What does the intermediate horn contain?
- Neurones of the sympathetic nervous system
Describe the formation of an apolar neuroblast
- Neuroblast migrates into mantle layer
- Loses its transient dendrite
- Becomes round and apolar
Describe the formation of a bipolar neuroblast
- Apolar neuroblast develops two cytoplasmic processes on opposite sides of the cell body (perikaryon)
Describe the formation of a multipolar neuroblast
- Cytoplasmic extensions of bipolar neuroblast develop a primitive axon and dendrite
What is a gliablast and how is it formed?
- Primitive supporting cell
- Formed when neuroepithelial cells stop producing neuroblasts
What type of glial cell develops in the mantle layer?
- Astrocyte
Identify two types of astrocytes and their role
- Protoplasmic astrocyte
- Fibrillar astrocyte
- Metabolic functions and support
What type of glial cell develops in the marginal layer?
- Oligodendroglial cell
What is the role of oligodendroglial cells?
- Myelin sheath in the ascending and descending axons in the marginal layer
What is the role of microglia and how is it formed?
- Highly phagocytic cell
- Formed from vascular mesenchyme when blood vessels grow into the nervous system
When are ependymal cells produced?
- When neuroepithelial cells stop producing both neuroblasts and glial cells
Where are ependymal cells located and what is their role?
- Central canal of spinal cord
- CSF production
When does myelination of peripheral nerves begin?
- Fourth month
Which cell type is responsible for myelination in the peripheral nerves?
- Schwann cells
How does myelination differ in Schwann cells and oligodendrocytes?
- Oligodendrocytes myelinate up to 50 axons
- Schwann cells myelinate a single axon
What is polyhydramnios and how is it detected?
- Feature of exencephaly
- Foetus lacks swallowing reflex
- Resulting in an excess of amniotic fluid in amniotic sac
- Which is detected on ultrasound (absent skull vault)
How much CSF is produced each day?
- 400 to 500 mL
Outline gender differences in bipolar disorder
- Similar incidence rates in men and women
- Women have later onset
- Bipolar II is more common in women
Outline attribution theory
- Individuals are motivated to see their social word as predictable and controllable - that is, a need to understand causality.
According to attribution theory, identify four criteria that are attributed to causality
- Distinctiveness
- Consensus
- Consistency over time
- Consistency of modality
According to attribution theory, outline four dimensions of attributions
- Internal versus external
- Stable versus unstable
- Global versus specific
- Controllable versus uncontrollable
What is meant by unrealistic optimism?
- The belief that individuals believe that they are unlikely to get a health problem
Identify three causes of unrealistic optimism
- Lack of personal experience with condition
- Condition is preventable
- Rarity of condition
Outline self-affirmation theory
- People are motivated to protect their sense of self-integrity
- If presented with information that threatens their sense of self, they behave defensively.
Identify the six aspects of health belief model
- Susceptibility
- Severity
- Perceived benefits
- Perceived barriers
- Cues to action
- Self efficacy
According to social cognition model, what is behaviour governed by?
- Expectancies
- Incentives
- Social cognitions
How does the Theory of Reasoned Action differ from the Theory of Planned Behaviour
- Theory of Reasoned Action focuses on subjective norms
- Theory of Planned Behaviour focuses on behavioural control
According to Protection Motivation Theory, health-related behaviour is influenced by which five components and which type of appraisal does each relate to?
- Severity (threat)
- Susceptibility (threat)
- Response effectiveness (coping)
- Self efficacy (coping)
- Fear (threat)
According to Protection Motivation Theory, people receive information that affects the five components from which two sources?
- Environmental
- Interpersonal
Outline Abortion Act 1967
- Pregnancy has not exceeded Week 24
- Termination requires two practitioners to believe:
- Mother / existing children physical or mental health at risk
- Pregnancy will result in permanent injury to the mother
- Child born with serious mental or physical abnormalities
Outline how capacity differs in 17 year olds to 13 year olds.
- Age 16 and 17 presumed to have capacity unless proven otherwise
- Age 14 and 15 presumed not to have capacity unless they meet Gillick competency criteria
- Age 13 or less unlikely to be Gillick competent
What should doctors do if child is not competent and parents refuse treatment.
- Consult courts if in best interests
- If in an emergency, act to save the child from death or serious harm.
Outline Gillick Competency
- Child is considered Gillick competent if:
- They are mature enough to understand the the nature, purpose, benefits and risk of treatment
- They can retain and use this information to communicate their decision.
Outline Fraser Guidelines
- Doctor should give advice to children with regards to sexual health if:
- Child is GIllick competent
- They cannot persuade the child to involve parents
- Physical or mental health would otherwise suffer (contraception is in best interests)
When may a doctor break confidentiality of a minor?
- Where health, safety or welfare of some person would otherwise be at serious risk.
- In cases of sexual activity involving children under 13, who are considered in law to be unable to give consent.
Outline how a patient is referred to an NHS specialist
- Referral, with letter, from GP
- If GP believes specialist referral is necessary
- Patient can choose the hospital under the NHS Choose and Book Scheme
What is clinical appraisal?
- Systematic examination of research to judge its validity, results and clinical relevance
Identify six components used as part of the critical appraisal checklist
- Originality
- Participants
- Study design
- Bias
- Blind
- Statistical questions
What is Critical Appraisal Skills Programme (CASP)?
- Provides critical appraisal checklists
- Designed to help one think about aspects of appraisal systematically
Which critical appraisal technique focuses on randomised control trials?
- CONSORT
Which critical appraisal technique focuses on cohort studies?
- STROBE
What is the purpose of systems used to rank or grade evidence?
- To guide users of clinical research about which studies are most likely to be most valid
Identify two systems used to grade or rank the quality of evidence
- GRADE
- SIGN
