Unit 14 week 4

Question 1

Localisation of function

Answer 1

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

Question 2

• Review brain anatomy

− Especially cranial nerves

− Sensory cortical regions

− Motor cortex

− Vasculature

− Blood-brain barrier, role in drug choices

Question 3

LIFESTYle and cqncer risk

Answer 3

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

Question 4

Potemtial causes of lump in breast

Answer 4

non-cancerous lump e.g., fibroadenoma, breast cyst, lipoma, puberty, , mastitis, cancer

Question 5

comparison of benign and malignant neoplasm

Answer 5

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

Question 6

Signs of breast cancer

Question 7

Anatomy of breast

Answer 7

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%)

Question 8

definitions of:

dysplasia

carcinoma in situ

invasive carcinoma

Answer 8

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

Question 9

Difference between hyperplasia and neoplasia

Answer 9

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

Question 10

Models of response to diagnosis

Answer 10

kubler ross 5 stages of grief

response can change over time e.g., reoccurence

Question 11

general pattern of referral

Answer 11

within 14 days

Question 12

examples of local therapy and systemic therapy for cancer

Answer 12

local: surgery, radiotherapy
systemic: chemo, hormonal, immuno

Question 13

What is a mammogram?

how is a needle core biopsy linked?

Answer 13

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

Question 14

general progression of normal cells to metastisis

Answer 14

Normal → Dysplasia → Carcinoma in situ → Invasive carcinoma

Question 15

is it the primary or secondary tumour that usually kills people?

Answer 15

secondary

Question 16

what are the cues for wide local excision rather than local excision

Answer 16

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)

Question 17

what is the sentinel lymph node procedure?

qhat are the general methods of cancer spread?

Answer 17

staging method which attempts to define how far a cancer has spread

1. lymphatics
2. blood
3. local
4. in body cavities

Question 18

Classification of tumours

Answer 18

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

Question 19

How are malignant tumours graded?

Answer 19

by biological aggresiveness:

1/2/3

or

well, moderately or poorly differentiated

Question 20

metastasis can be split into 5 basic steps:

Answer 20

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

Question 21

relevence of headaches in the morning and cancer

Answer 21

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

Question 22

hypertonia

hyperreflexia

aphasia

Answer 22

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).

Question 23

common differential diagnosis for brain dysfunction

Answer 23

ischaemic stroke

haemorrhagic stroke

lesion to cranial nerves

lesion to motor tracts

Question 24

brain anatomy- cortex landamarks

Question 25

damage to brocca's and Wernicke's area

Answer 25

**Broca’s area** produces coherent speech (damage causes Expressive aphasia) **Wernicke’s area** (superior temporal area) is required for comprehension (damage causes Receptive aphasia)

Question 26

mass effect midline shifts odema

Answer 26

▪ **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

Question 27

frontal and parietal lobes of the brain + pons and effect of tumour in each

Answer 27

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Question 28

Differentiating between upper and lower motor neurone lesion

Answer 28

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) ![]()

Question 29

association commissural projection fibres in the brain

Answer 29

**_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

Question 30

Her-2 positive cancer therefore which drug should you use as chemotherapy?

Answer 30

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

Question 31

alternative target for anti breast cancer drugs?

Answer 31

oestrogen receptor

Question 32

grading lymoh node involvement

Answer 32

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Question 33

large molecular weight limits delivery across the blood brain barrier but:

Answer 33

* radiotherapy damages BBB endothelium, increasing permeability * neurovascularistion in tumours are already leaky

Question 34

dexamethasone

Answer 34

* **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 mRN**A and s**ubsequent protein synthesis** (e.g., decreased anti-inflams) upregulate tight junction protein occludin and cadherin ![]()

Question 35

name some psychological and behavioural interventions available to cancer patients

Answer 35

Behavioural therapy for pain and nausea - Educational therapy to improve coping skills, - Psychotherapy to reduce anxiety and depression - Support groups

Question 36

which 3 cn's contribute to eye movement? what movements do they control?

Answer 36

oculomotor III- elevates, depresses, adducts trochlear IV- medial + depression??? abducens VI- abduction ![]()

Question 37

cn responsible for sensation on the face

Answer 37

trigeminal nerve facial nerve for ear way

Question 38

cranial nerves involved in taste

Answer 38

Olfactory is Ist cranial nerve; - Sense of taste via facial VIIth - Glossopharyngeal IXth

Question 39

What kind of particles bind to olfactory receptors? messenger system of olfactory receptors? where do olfactory projections go?

Answer 39

airbone molecules G protein coupled receptor and cAMP-gated channels projections to temporal lobe (pyriform cortec and limbic system) and then to hypothalamus

Question 40

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?

Answer 40

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

Question 41

olfactory pathway

Answer 41

1. ***_Olfactory nerve pathway_*** 2. Originates in **olfactory receptors** within **nasal epithelium**. 3. **Axons** (known as fila olfactoria) **assemble into bundles of true olfactory nerves** which **penetrate small foramina in cribriform plate of ethmoid bone**. 4. **Fibres enter olfactory bulb** which lies in olfactory groove within anterior cranial fossa. 5. Olfactory nerve fibres synapse with specialised neurones called mitral cells in olfactory bulb – this forms collections known as synaptic glomeruli. 6. From here **second order neurons pass posteriorly into olfactory tract**. 7. Olfactory tract travels posteriorly on inferior surface of frontal lobe then divides into medial and lateral stria: 8. Lateral stria – carries axons to primary olfactory cortex within temporal lobe. 9. Medial stria – carries axons across medial plane of anterior commissure where they meet the olfactory bulb of the opposite side.

Question 42

Bell's palsy pathphysiology symptoms

Answer 42

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

Question 43

distinguish between bells palsy and ischaemic stroke

Answer 43

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

Question 44

accronym for breaking bad news

Answer 44

**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

Question 45

dorsal column medial lemniscus pathway

Answer 45

vibration, proprioception and fine touch ![]()

Question 46

Anterolateral system- spinothalamic tract

Answer 46

**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 ![]()

Question 47

give 2 examples of breat cell cancer

Answer 47

ductal carcinoma lobule carcinoma

Question 48

BBB and choice of drug

Answer 48

only ways through the BBB are: 1. **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. 2. **Small, lipid-soluble agents**, such as antidepressants, cross the BBB through diffusion t**hrough the endothelial cells**. 3. **Specialized transport proteins** transport glucose, amino acids and drugs such as cyclosporin across the BBB 4. **Receptors** mediate transcytosis of proteins like insulin 5. 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.