Unit 14 week 4 Flashcards
Localisation of function
Specific neurological dysfunctions arise based on tumour/lesion location, indicating that there are neural areas/pathways dedicated to speech, language, motor control, and brain stem functions
Neurological deficits can indicate lesion location
• Review brain anatomy
− Especially cranial nerves
− Sensory cortical regions
− Motor cortex
− Vasculature
− Blood-brain barrier, role in drug choices
LIFESTYle and cqncer risk
no link between cortisol and cancer formation
however those that are more stressed tend to engage in cancer promoting behaviours e.g., smoking, drinking alcohol, overreating
Potemtial causes of lump in breast
non-cancerous lump e.g., fibroadenoma, breast cyst, lipoma, puberty, , mastitis, cancer
comparison of benign and malignant neoplasm
Neoplasm:
Benign
Malignant/cancerous
Definition
Slow-growing, non-invasive cells with lost proliferation control. If mass of cells, can call tumour (solid or fluid-filled). Lymphoma, leukaemia
are neoplasias but not tumours.
Invasive (local) or metastatic (distant) spread
Cells
May be heterogeneous
Clonal, essentially immortal
Capsule
(fibrous)
Typically present
Usually absent
Borders
Typically smooth, sharply demarcated
Irregular
Signs of breast cancer
Anatomy of breast
anterior thoracic wall
at the centre of the breast is the areola which contains sebaceous glands
contains mammory glands- involved in lactation and controlled by pituitary
fibrous troma condenses to form suspensory ligaments which secures the breast to the dermis of the underlying pectoral fascia
supplied by the internal thoracic artery medially and the lateral thoracic + thoracromial laterally
3 groups of lymoh nodes receive drainage from the breast:
axillary nodes (75%)
parasternal (20%)
posterior intercostal (5%)
definitions of:
dysplasia
carcinoma in situ
invasive carcinoma
dysplasia- Cellular proliferation (hyperplasia) showing some but not all the molecular and morphological characteristics
carcinoma in situ- Severe dysplasia without spread across the limiting basement membrane: thus without invasion of tissue and without metastatic potential. Usually treated, due to high risk of developing into cancer. Removal is considered cure
invasive carcinoma- Cancer
Difference between hyperplasia and neoplasia
Hyperplasia is a physiological (normal) response to a stimulus that leads to normal cell proliferation and enlargement of a tissue
Neoplasia is an abnormal cell proliferation in a non-physiological manner, which is unresponsive to a stimulus
Models of response to diagnosis
kubler ross 5 stages of grief
response can change over time e.g., reoccurence
general pattern of referral
within 14 days
examples of local therapy and systemic therapy for cancer
local: surgery, radiotherapy
systemic: chemo, hormonal, immuno
What is a mammogram?
how is a needle core biopsy linked?
A mammogram is an X-ray examination of the breast showing extent of the tumour and may indicate benign or malignant processes- Ultrasound may also be used
Needle core biopsy can be guided using the mammogram, producing tissue for histological examination
general progression of normal cells to metastisis
Normal → Dysplasia → Carcinoma in situ → Invasive carcinoma
is it the primary or secondary tumour that usually kills people?
secondary
what are the cues for wide local excision rather than local excision
well transcribed, no evidence of spread
▪ A wide local excision is performed for cancer (due to infiltrative margins), extending beyond the apparent clinical surgical or radiological margin (benign tumours often removed with a narrow margin)
what is the sentinel lymph node procedure?
qhat are the general methods of cancer spread?
staging method which attempts to define how far a cancer has spread
- lymphatics
- blood
- local
- in body cavities
Classification of tumours
tumours based on primary site, cell type and cellular morphological predictors of behaviour
primary site: breast, colon,
cell type: epithelial, CT, melanocytic
morphological predictors of behaviour: [architectural disorganisation, pleomorphism (size/shape variation), mitoses, nuclear hyperchromasia (more intense chromatin staining), necrosis, invasion of tissues/blood vessels/lymphatic channels, differentiation (similarity to corresponding normal tissue)].
Benign
Malignant
Epithelium any type
Add -oma
Carcinoma
Epithelium from glandular organs e.g. breast, stomach, colon, prostate
Adenoma
Adeno-carcinoma
Epithelial from a squamous tissue e.g. skin, mouth, larynx, lung [after metaplasia i.e. change of one mature cell type to another]
Squamous cell papilloma
Squamous cell carcinoma
Epithelium of transitional type e.g. bladder
Transitional cell papilloma
Transitional cell
carcinoma
Connective tissue Fat
Chondrocyte Blood vessels
Add - oma
LipomaChondroma
Angioma
-sarcoma
Lipo sarcoma
Chondro sarcoma
Angiosarcoma etc
How are malignant tumours graded?
by biological aggresiveness:
1/2/3
or
well, moderately or poorly differentiated
metastasis can be split into 5 basic steps:
1) invasion of the basement membrane and cell migration
- cells mechanically remodel the ECM through a cycle of cell protrusion and contraction
- they chemically degrade the ECM using MMPs
- become motile by undergoing epithelial to mesenchymal transition
2) intravastion into surrounding vasculature or lymphatic system
* tumour angiogenesis brings nutrients to the gorwing mass of cells while also offering them a route into the circulatory system for haematogenous spread
3) survival in circulation
within the blood stream, the cancer must survive:
a) haemodynamic forces
b) immune stresses
c) red blood cell collisions
* the tumour cells undergo mutations which allow them to survive e.g., PAR2 proteins recruit adaptor proteins to mediate cancer cell migration.
4) Extravasation from vasculature into secondary tissue
- involves a cascade of events inc. the tumour cell arrest on the endothelium and making contact with platelets. cell displaces an endothelial cell in the lining
- invsation of surrounding tissue
5) colonisation at secondary tumour site
relevence of headaches in the morning and cancer
intracranial pressure is greatest when horizontal
not specifically alarming but you should still refer to neurology???
cancers can cause headaches as they are space occupying lesions
hypertonia
hyperreflexia
aphasia
Hypertonia is likely a central nervous system deficit: upper motor neuron, basal ganglia or frontal lobes
▪ Hyperreflexia: increased speed or amplitude; presence helps localise lesion
aphasia
language impairment, either speech or comprehension: (students should)
understand basics of producing speech, in that it involves shaping the tongue, lips, vocal folds (within larynx).
common differential diagnosis for brain dysfunction
ischaemic stroke
haemorrhagic stroke
lesion to cranial nerves
lesion to motor tracts
brain anatomy- cortex landamarks
damage to brocca’s and Wernicke’s area
Broca’s area produces coherent speech (damage causes Expressive aphasia)
Wernicke’s area (superior temporal area) is required for comprehension (damage causes
Receptive aphasia)
mass effect
midline shifts
odema
▪ Mass effect implies mass(es) with possible oedema…… May impose pressure on CNS structures, impairing function
▪ Often causes midline shifts with increased complications, contralateral signs, hydrocephalus, increased intracranial pressure
oedema is the cause–> leaky blood vessels due to inflammation
skull is a rigid structure with little space unoccupied in it. increased intracranial pressure can lead to spinal cord hernation or injury which can be fatal
frontal and parietal lobes of the brain + pons and effect of tumour in each
Differentiating between upper and lower motor neurone lesion
UMN
lesions occur in the brain or spine- i.e. they lead to a lack of higher control:
- Pyramidal weakness, ie flexors stronger than extensors in arms, extensors stronger than flexors in legs
- Spasticity
- Brisk reflexes
- Upgoing (extensor) plantar reflex
- Clonus- nvoluntary muscle contractions. This results in uncontrollable, rhythmic, shaking movements
LMN
lesions occur in the nerve root, plexi or peripheral nerve
Flaccid weakness
Normal or reduced tone
Reduced or absent reflexes
Wasting
Fasciculation (ie no nerve supply)
association
commissural
projection fibres in the brain
association- white matter tract that connects 2 areas within the same hemisphere
commissural/ transverse- connect 2 hemispheres through the corpus callosum
projection- type of white matter tract that connects the cortex with other areas of the CNS e.g., to brainstem or spine
Her-2 positive cancer therefore which drug should you use as chemotherapy?
trastuzumab
CLASS: recombinant IgG1 kappa humanised monoclonal antibody
INDICATION: HER2+ metastatic breast cancer. HER-2 triggers downstream signalling when bound to EGF and cell proliferation. monotherapy or as adjunct to cis-platin
PHYS: Target: extracellular domain of HER-2 action: nhibition
- downstream signalling involves Ras/ Raf/ mitogen-activated protein kinase (MAPK) that acticates cell prolif and growth.
- inhinbits angiogenesis and activates antibody-dependant cell-mediated cytotoxicity
Side effects: anxiety, alopecia, appetite, depression
alternative target for anti breast cancer drugs?
oestrogen receptor
grading lymoh node involvement
large molecular weight limits delivery across the blood brain barrier but:
- radiotherapy damages BBB endothelium, increasing permeability
- neurovascularistion in tumours are already leaky
dexamethasone
- Unbound corticosteroids diffuse through the plasma membrane and bind to the cytoplasmic corticosteroid receptor, allowing the steroid–receptor complex to move into the nucleus.
- In the nucleus, glucocorticoids bind directly to specific DNA sequences called glucocorticoid response elements (GREs) that regulate the transcription of nuclear DNA.
- Downstream, this affects the production of mRNA and subsequent protein synthesis (e.g., decreased anti-inflams)
upregulate tight junction protein occludin and cadherin
name some psychological and behavioural interventions available to cancer patients
Behavioural therapy for pain and nausea
- Educational therapy to improve coping skills,
- Psychotherapy to reduce anxiety and depression
- Support groups
which 3 cn’s contribute to eye movement?
what movements do they control?
oculomotor III- elevates, depresses, adducts
trochlear IV- medial + depression???
abducens VI- abduction
cn responsible for sensation on the face
trigeminal nerve
facial nerve for ear way
cranial nerves involved in taste
Olfactory is Ist cranial nerve;
- Sense of taste via facial VIIth
- Glossopharyngeal IXth
What kind of particles bind to olfactory receptors?
messenger system of olfactory receptors?
where do olfactory projections go?
airbone molecules
G protein coupled receptor and cAMP-gated channels
projections to temporal lobe (pyriform cortec and limbic system) and then to hypothalamus
taste receptors are clustered into what on the tongue?
what are the modalities of taste? how are they transduced?
anterior 2/3 of tongue taste is conveyed by:
posterior third by:
taste projections are to the?
papillae
sweet, salt, bitter, sour, umami
mediated by effects on ion channels via G proteins or via cAMP-gated channels
anterior 2/3 via chorda tympani of the facial nerve (VII)
posterior 1/3 via the glossopharyngeal nerve (IX)
taste projections: nucleus tractus solitarius in the medulla –> thalamus –> somatosensory and insular cortex
olfactory pathway
- Olfactory nerve pathway
- Originates in olfactory receptors within nasal epithelium.
- Axons (known as fila olfactoria) assemble into bundles of true olfactory nerves which penetrate small foramina in cribriform plate of ethmoid bone.
- Fibres enter olfactory bulb which lies in olfactory groove within anterior cranial fossa.
- Olfactory nerve fibres synapse with specialised neurones called mitral cells in olfactory bulb – this forms collections known as synaptic glomeruli.
- From here second order neurons pass posteriorly into olfactory tract.
- Olfactory tract travels posteriorly on inferior surface of frontal lobe then divides into medial and lateral stria:
- Lateral stria – carries axons to primary olfactory cortex within temporal lobe.
- Medial stria – carries axons across medial plane of anterior commissure where they meet the olfactory bulb of the opposite side.
Bell’s palsy pathphysiology
symptoms
The facial nerve courses through a portion of the temporal bone commonly referred to as the facial canal. A popular theory proposes that edema and ischemia result in compression of the facial nerve within this bony canal.
symptoms:
- weakness in facial muscles
- makes half of the face droop
- mouth droops ad eye resists closing
- drooling
- loss of taste
- weakness is temporary
distinguish between bells palsy and ischaemic stroke
stroke spares forehead and patient can raise eyebrows symmetrically
bell’s palsy should not have anhy limb effects
bells temporary
treat with prednisolone and facial exercises
accronym for breaking bad news
Setting- arrange for privacy and practice what you’ll say
Perceptions- elicit the patient’s perception
Invitation- ask the patient what they would like to know
Knowledge- provide info in small pieces
Emotions- recognises and empathises with emotions
Strategy and summary- set out a pan of action and to meet again
dorsal column medial lemniscus pathway
vibration, proprioception and fine touch
Anterolateral system- spinothalamic tract
anterior segment- crude touch and pressure
lateral segment- pain and temperature
decussates at the level of the spinal cord in which it enters
ascending tract
give 2 examples of breat cell cancer
ductal carcinoma
lobule carcinoma
BBB and choice of drug
only ways through the BBB are:
- Passive movement of water-soluble agents across the BBB cannot be facilitated due to the close nature of the tight junctions between the endothelial cells.
- Small, lipid-soluble agents, such as antidepressants, cross the BBB through diffusion through the endothelial cells.
- Specialized transport proteins transport glucose, amino acids and drugs such as cyclosporin across the BBB
- Receptors mediate transcytosis of proteins like insulin
- Proteins, such as albumin are absorbed and transported via transcytosis (through the cell) Efflux transporters counter passive diffusion by pumping foreign agents out of the brain.
