Anaesthetics and Genetics

Question 1

Triad of anaesthesia

Answer 1

Analgesia
Hypnosis
Relaxtion

Question 2

What is analgesia

Answer 2

Pain relief/protection from painful stimuli

usually required even if unconscious to suppress reflex autonomic responses

Question 3

What is hypnosis

Answer 3

Unconsciousness - necessary for general

Question 4

What is relaxation

Answer 4

muscle relaxation to provide immobility and allow access to cavities and artificial ventilation

Question 5

General anaesthetics agents

Answer 5

suppress neuronal activity in dose dependent fashion

Hyperpolarise neurons

Question 6

Inhalational general agents

Answer 6

Dissolve in membranes
Halogenated hydrocarbons
Uptake and exertion via lungs
MAC = minimum alveolar concentration, measure of potency - low number=high potency
Induction slow
Main role in maintenance of analgesia

Question 7

how is function lost in general agents

Answer 7

Cerebral function lost from top down
LOC early - hearing later
Reflexes relatively spared

Question 8

IV general agent

Answer 8

E.g. thiopentone, propofol
allosteric binding on GABA receptors
Rapid onset of uncosciousness
Can only cause temporary LOC if given as one off bolus

Question 9

Sequence of GA

Answer 9

Can use inhalation for induction then inhalation for maintenance or can use IV for induction and then use IV or inhalation for maintenance
Most common IV followed by inhalational

Question 10

GA effect on CVS

Answer 10

Depress CVS centre
Vasodilation and venodilation
Negatively inotropic
Reduced venous return and fall in CO

Question 11

GA effect on resp

Answer 11

Respiratory depressants - reduce hypoxic and hypercarbic drive, decreased TV and increase rate
Paralyse cilia
Decrease FRC - lower lung volumes and VQ mismatch

Question 12

Features of muscle relaxants

Answer 12

relax skeletal muscles

If systemic then unconsciousness must be provided so not paralysed but awake

Question 13

Indications for muscle relaxants

Answer 13

ventilation and intubation
When immobility essential
Body cavity surgery

Question 14

Problems with muscle relaxants

Answer 14

Awareness - paralysis but awake
Incomplete reversal - airway obstruction
Apnoea = dependence on airway and ventilatory support

Question 15

Features of intraoperative anaglesia

Answer 15

prevention of arousal

Supression of reflex responses to painful stimuli

Question 16

Features of LA

Answer 16

Lignocaine, bupivacaine
Sodium channel blockers
Acts indiscriminently on range of tissues
Prevent propagation of action potential
Must be unionised to cross membranes (inflamed tissue with low pH relatively resistant to LAs)
Limiting factor in use is toxicity

Question 17

Signs and symptoms of LA toxicicty

Answer 17

Circumoral and lingual numbness and tingling
Light headedness
Tinnitus, visual disturbance
Drowsiness
CVS depression
Convulsions
Coma
Cardiorespiratory arrest

Question 18

Difference between maintained and protected airway

Answer 18

Aiway maintained if open and obstructed

Only cuffed tube in trachea protects airway from contamination

Question 19

Features of endotracheal intubation

Answer 19

Placement of cuffed tube in trachea
Laryngeal reflexes must be abolished
Laryngoscope muscle relaxant
Also possible in awake patient using local anaesthetic and fibre optic scope

Question 20

Why intubate?

Answer 20

Protect airway from gastric contents
Need for muscle relaxation
Shared airway with risk of blood contamination (tonsillectomy)
Need for right control of blood gases
Restricted access to airway

Question 21

Features of germline mutations

Answer 21

Present in egg or sperm
Inheritable
Cause cancer family syndrome

Question 22

Features of somatic mutations

Answer 22

Occur in non germline tissues

Are non inheritable

Question 23

What are oncogenes

Answer 23

normal genes that regulate cell growth
first mutation leads to susceptible carrier
second mutation or loss leads to cancer

Question 24

What is multistep carcinogenesis

Answer 24

normal epithelium –> hyper proliferative epithelium –> early adenoma –> intermediate adenoma –> late adenoma –> carcinoma –> metastasis

Question 25

What is retinoblastoma

Answer 25

Medical emergency White pupillary reflex Tumour of lining of eye

Question 26

Features of heridatary non-polyposis colon cancer

Answer 26

Mutation in mismatch repair gene Excess of colorectal, endometrial, urinary tract, ovarian and gastric cancers Opportunity for prevention by colonoscopy Clinical features - early but variable age at CRC diagnosis (45), tumour site in proximal colon predominates)

Question 27

BRCA 1 and 2 features

Answer 27

Increased breast and ovarian cancer risk | Males increased risk of prostate and breast cancer

Question 28

Autosominal dominance inheritance features

Answer 28

Each child has 50% chance of inheriting alteration No 'skipped' generations Equally transmitted by men and women

Question 29

When to suspect hereditary cancer syndrome

Answer 29

Cancer in 2 or more close relatives (same side) Early age at diangosis Multiple primary tumours Bilateral or multiple rare cancers Characteristic pattern of tumours (breast and ovary) Evidence of autosomal dominant transmission

Question 30

Breast cancer surveillance features

Answer 30

Early clinical surveillance 5 year less 1st cancer in family Mammography 2 early from 35-40, yearly 40-50 (high 18 monthly 50-64) Prophlyactic masectomy - total removes more than subscutaneous

Question 31

Prophylactic oopherectomy

Answer 31

Eliminates risk of primary ovarian cancer | Induces surgical menopause HRT till 50 does not change BRCA risk

Question 32

Modes of inheritance in multi-system disorders

Answer 32

NEw mutation or inherited Chromosomal SIngle gene disorders Multifactorial

Question 33

What is Li-fraumeni syndrome

Answer 33

increased risk developing cancer Autosomal dominant Breast, osteosarcoma, soft tissues

Question 34

What is inheritance of CF

Answer 34

Autosomal recessive

Question 35

What is inheritance of myotonic dystrophy

Answer 35

Autosomal dominant

Question 36

Neurofibromatosis type 1 features

Answer 36

Autosomal dominant 2+ of diagnostic criteria fro diagnosis Tumour supressor gene

Question 37

Neurofibromatosis diagnostic features

Answer 37

``` Cafe au last spots - more than 6 Neurofibromas - 2 or more Axillary freckling Lisch nodules Optic glioma - field deficits, blindness Thinning of long bone cortex - bent tibia Family history ```

Question 38

Management of neurofibromatosis

Answer 38

Annual review of affected individuals and at risk children till diagnosis excluded BP Spine for scoliosis Tibia for unusual angulation Visual acuity and visual fields Educational assessment Ask patient to report any unusual symptoms

Question 39

Tuberous sclerosis features

Answer 39

Classic triad - epilepsy, learning difficulty, skin lesions Autosomal dominant Hamartomas in different organs 2 genes on different chromosome both cause TS with identical phenotypes (TSC1 and TSC2)

Question 40

Clinical features of tuberous sclerosis

Answer 40

``` Multi-system Variable expression Learning difficulty Seizures Depigmented macules Angiofibromas Fibrous plaque forehead Shagreen patches Ungula fibromas Kidney cysts and angiomyolipomata Rhabdomyomas in heart Phakomas in eye ```

Question 41

Screening of at risk relatives of tuberous sclerosis

Answer 41

Siblings and parents may be mildly affected Surveillance and genetic counselling Clinical examination - skin signs, retinal exam Cranial MR scan Renal ultrasound Echo

Question 42

Features of myotonic dystrophy

Answer 42

Autosomal dominant CTG repeat, exhibits anticipation with increasing severity in each generation Bilateral late onset cataract Muscle weakness, stiffness and myotonia Low motivation, bowel problems, DM Death post anaesthetic risk if not monitored

Question 43

Features of ALS

Answer 43

General sporadic Mean age onset 55 years - younger in familial forms 5-10% familial (AD and AR)

Question 44

Clinical features of ALS

Answer 44

``` Progressive muscle weakness, wasting and increased reflexes Limb and bulbar muscles involved Pure motor signs Cognition spared Death due to respiratory failure ```

Question 45

Huntington's features

Answer 45

Autosomal dominant Adult onset Unique mutation - CAG expansion Movement disorder - chorea, athetosis, myoclonus, rigidity Cognitive changes - poor planning and memory, subcortical dementia Personality change Psychiatric disease - depression, paranoia, psychosis Onset late 30s-early 40s Fully penetrant