Actively dividing cells undergo a series of stages known as the cell cycle.
- Gap 0 (G0; quiescent phase)
- Most non-proliferative cells in the body are in this phase and are not actively replicating.
- Gap 1 (G1)
- Metabolic changes prepare the cell for division. At a certain point (restriction point or G1 checkpoint), the cell is committed to division and moves onto S-phase
- Synthesis phase (S phase)
- DNA synthesis replicates the genetic material such that each chromosome is duplicated into two chromatids
- Gap 2 (G2)
- Metabolic changes assemble the cytoplasmic materials required for mitosis and cytokinesis
- Mitotic phase (M phase)
- Nuclear membrane breaks down into a number of small vesicles
- Centrosome duplicates and each one migrates to opposite poles of the cells where they organise production of microtubules that form spindle fibres (mitotic spindle)
- Chromosomes condense into compact structures. Sister chromatids are held together via the centromere structure
- Chromosomes migrate to the middle of the cell (the metaphase plate).
- Spindle fibres attach to centromeres of the chromosomes.
- Chromosomes align along the metaphase plate
- Centromeres divide and daughter chromatids are pulled apart by spindle fibres
- Nuclear membrane reforms around the new chromosomes at either pole of the cell.
- Chromosomes uncoil and become diffuse once more and spindle fibres are broken down
- Constriction of the cytoplasm to divide into two new cells.
See also Diabetes and Surgery
- Statins can be continued as normal
- Beta-blockers can be continued (but should not be started if patient was not previously taking them)
- Antiplatelets should be withheld 7-14 days prior
- ACE inhibitors and ARBs should be withheld the day of surgery (they can cause marked hypotension with GA)
- Diuretics should also be withheld on the day of surgery
- Warfarin should be withheld 3-5 days before surgery (see below)
- Calcium channel blockers can be continued
- Pre-operative risk and management
- Get a cardiology review if there is any concern over the patient’s fitness for surgery
- For patients undergoing non-cardiac surgery, the ACC/AHA have produced the following guide flow-chart
- Using the Revised Lee Cardiac Index (RLCI)
- Any 2 or more of the following would be high risk (>1% risk of major cardiac event)
- PMHx of MI, (positive ETT, Angina, use of GTN, ECG with pathological Q waves or signs of ischaemia)
- PMHx of CCF/HF; (pulmonary oedema, PND, bilateral rales or S3 gallop, CXR showing pulmonary vascular redistribution)
- PMHx of stroke/TIA
- Preoperative treatment with insulin
- Preoperative eGFR <30ml/min
- **METs** (Metabolic equivalent- 1= 3.5ml O2 uptake/kg/min (resting O2 intake))
- These are similar to assessing someone’s exercise tolerance
- Self care, eat, dress, toilet etc – 1 MET
- Walk up a flight of stairs/hill or walk briskly for prolonged time (~4 METs)
- Can do heavy work, or climb 2 flights of stairs (6-10 METs)
- Can do strenuous exercise (10+ METs)
- In patients with unstable Coronary artery disease, it may be appropriate to perform revascularisation (PCI) prior to surgery. However, this would only represent a minority of patients.
- Patients with Valvular disease (in particular stenoses) should be considered for peri-operative antibiotic therapy to reduce the risk of endocarditis
- Make sure to monitor any signs of silent ischaemia (cardiac monitoring) and heart failure
- The main issue with surgery in patients with respiratory disease is due to anaesthesia
- Sedation can cause hypoventilation and atelectasis, worsening hypoxaemia and hypercapnia, increased V/Q mismatch
- Airway manipulation can cause a reactive bronchospasm which can be severe in patients with airways disease
- Controlled ventilation may cause impaired airflow and increased hyperinflation of the lungs in patients with COPD (and even ‘dynamic hyperinflation’ i.e. continuous inflation of the lungs
- As such, if possible, avoid general anaesthesia (i.e. use regional anaesthesia)
- Assessing/managing risk
- Pulmonary function tests are crucial. Note that most operations will result in a reduction in pulmonary function peri- and postoperatively, and this should be taken into account when deciding if surgery is appropriate
- Deep breathing exercises +/- chest physiotherapy/rehabilitation is often useful in patients with COPD to improve function prior to surgery
- If FEV1/FVC ratio <50%- risk of respiratory failure following surgery is increased dramatically
- Smoking cessation- this will reduce the risk of post-operative complications including wound healing and pulmonary complications
- Intra-operative PEEP (positive end expiratory pressure) and post-operative non-invasive ventilation (CPAP or BIPAP) may prevent respiratory failure
- Make sure to correct any exacerbations prior to surgery
- Inhalers/nebulisers should be taken pre-operatively (ideally close to induction)
- For steroid use, see below
- Note that anaesthetic drug choice may be important
- Nitrous oxide may rupture bullae in COPD and cause pneumothorax
- Opiates usually cause respiratory depression
- Post operative pain may result in respiratory depression
- General anaesthesia
- Reduces muscle tone and thus residual capacity
- Increases airway resistance and reduces lung compliance
- Causes atelectasis in dependent zones (causing increased V/Q shunting)
- Increases ventilatory dead space
- Contraindications to surgery include Acute or fulminant hepatitis, alcoholic hepatitis and severe chronic hepatitis
- For other patients with liver disease, there are several scoring systems used to categorise risk (Child-Pugh and MELD scores)
- In general, CP class A/MELD score <10 can undergo elective surgery; CP class B/MELD score 10-15 can undergo elective surgery with caution (see below) and CP class C/MELD score >15 should not undergo elective surgery
- In patients with prolong PT- vit K can be given pre-operatively to correct this
- In patients with ascites and oedema, diuretics may be used to reduce this (alternatively ascites may be drained intraoperatively)
- Electrolyte abnormalities should be corrected and renal function evaluated/optimised.
- Patients with gastroesophageal varices should be treated optimally (whether with betablockers/nitrates or with banding/ligation) prior to surgery
- Where possible, correct any jaundice prior to surgery
Diabetes (see diabetes and surgery)
- Potential adverse outcomes
- Low cardiac output and increased risk of CVD (increased risk of MI; hypotension)
- Blood loss poorly tolerated
- Respiratory centre less responsive to O2 and CO2 pressures (hypoventilation; acidosis)
- More sensitive to opiates
- In overt hypothyroidism- correction (levothyroxine) should ideally be given prior to surgery where possible
- In severe cases (myxoedema coma)- T3 and T4 may be given prior to surgery
- Increased risk of
- tachycardia; labile BP and arrhythmias (increased output and contractility due to increase in O2 demand)
- dyspnoea (similar reason)
- Thyroid storm- an uncontrolled release of thyroid hormone. Causes hyperthermia and metabolic acidosis (high mortality)
- Note that treatment is the same as for hyperthyroidism but increased dose/frequency and adequate ITU support.
- Ideally controlled with carbimazole or propylthiouracil prior to surgery
- If surgery is urgent and hyperthyroidism not controlled- potassium iodide drops may temporarily halt to the release of hormones (not temporarily)
- Propanolol can be used for symptomatic relief
A note about some drugs
- Ideally, patients should not be on steroids, as they can lead to
- Poor wound healing
- Impaired glucose tolerance
- Muscle wasting
- Electrolyte disturbances
- Masking of sepsis
- However, patients that are taking or have recently (< 3 months) taken steroids at a dose of >10mg/day are at risk of adrenocorticoid insufficiency should they be stopped.
- Peri-operatively, this could potentially cause cardiac failure or an Addisonian crisis
- As such, steroids should be given to cover for this in these patients
- Dosing equivalents: Prednisolone 10 mg is equivalent to Betamethasone 1,5 mg or Cortisone acetate 50 mg or Dexamethasone 1.5 mg or Hydrocortisone 40 mg or Deflazacort 12 mg or Methylprednisolone 8 mg
- Due to the risk of bleeding, warfarin should ideally be stopped 3-5 days prior to surgery (INR <1.5)
- If the risk of thrombosis is high (e.g. metallic heart valve); then warfarin should be replaced with heparin. If the risk is relatively low e.g. AF (without previous CVA), then it may be possible to stop without any heparin substitute.
- Antiplatelet agents (aspirin, clopidogrel etc)
- Should be stopped 7-14 days prior to surgery due to risk of bleeding.
- Should be continued where possible
- CN I/Olfactory nerve is the shortest cranial nerve and consists of special unmyelinated sensory nerves responsible for sense of smell
- They are, however, covered in Schwann cells
The olfactory pathway
- Odourant molecules can enter your system via your nose or mouth and nasopharynx.
- They reach an area called the olfactory mucosa in the nasal cavity
- Here, they come into contact with the olfactory receptor neurons and activate receptors to initiate an action potential
- The axons of these cells traverse the cribiform plate of the ethmoid bone at the roof of the nasal cavity and become the olfactory bulb.
- In the bulb, these neurons communicate with specialised mitral cells at the synaptic glomeruli. These then pass posteriorly into the olfactory tract
- This runs along the inferior aspect of the frontal lobe. At the anterior perforated substance, the tract divides into medial and lateral stria.
- Medial stria connects to the limbic system and communicates with the contralateral olfactory medial stria
- Lateral stria continues to the primary olfactory cortex in the temporal lobe, which goes on to communicate further with the limbic system (amygdala, piriform cortex and olfactory tubercle) and orbitofrontal cortex.
- CN I is covered by pia and arachnoid layers (i.e. continuation of the brain). It does also not join with the brainstem.
- The olfactory nerve is capable of regeneration.
Olfactory Dysfunction (Anosmia)
- Temporary anosmia is not uncommon in local conditions of the nose e.g. infection.
- Other causes of anosmia/abnormal sensation of smell include
- Tumours in the olfactory groove (meningioma)
- Head injury- damage to the cribiform plate may cause damage to the olfactory receptors
- Neurodegenerative disease e.g. Parkinson’s Disease, Huntington’s and Alzheimer’s disease
- Genetic conditions e.g. Kallman Syndrome, Primary ciliary dyskinesia, Foster Kennedy Syndrome
- Partial epilepsy (pre- and post-ictal)
Testing CN I
- Ask the patient if they have noticed a change in their sense of smell.
- A more formal assessment of smell can involve using common smells
An ECG abnormality with a high incidence of sudden death in patients with structurally normal hearts.
- Most cases due to a mutation in a cardiac sodium channel gene (sodium channelopathy)
- Most are spontaneous but occasionally there are hereditary cases
- NB Can be transient and/or can be unmasked/augmented by a number of factors e.g. fever, ischaemia, drugs (notably sodium channel blockers e.g. flecainide; calcium channel blockers; alpha receptor agonists; beta blockers; nitrates; cocaine; alcohol), hypokalaemia, hypothermia, cardioversion
- ECG findings
- Type 1
- Coved ST segment elevation >2mm in >1 of V1-V3, followed by a negative T wave (Brugada sign)
- Note that this is the only sign that is potentially diagnostic. It must be associated with one of the following to make the diagnosis:
- Episode of VF or polymorphic VT
- Family history of sudden cardiac death <45 years old
- Coved type ECGs in family members
- Inducibility of VT with programmed electrical stimulation
- Nocturnal agonal respiration
- Type 2 sign has >2mm of saddleback shaped ST elevation and type 3 can be either morphology but with <2mm elevation
- Where the patient is asymptomatic, it may be appropriate to carry out electrophysiological testing to try and induce VT in patients with ECG changes. However, this is often not conclusive and does carry significant risk.
- Alternatively, attempting to induce VT with a dose of flecainide may also help with diagnosis, but has similarly poor diagnostic capability and can be dangerous.
- The only proven management for Brugada syndrome is an ICD device.