Physiology 19 Flashcards
What preoperative factors can contribute to the stress response to surgery?
- Personality
- Preoperative mental state
- Dehydration
- Partial starvation
Define the stress response
The combination of hormonal, inflammatory, metabolic and psychological changes which occur in response to trauma or surgery
What perioperative factors can contribute to the stress response to surgery?
- Haemorrhage
- Hypothermia
- Pain
What postoperative factors can contribute to the stress response to surgery?
- Pain
- Immobilisation
- Hypoxia
- Alterations in diurnal rhythm
Outline the pituitary response to stress
Increased anterior pituitary secretion of:
- ACTH
- GH
- β endorphin
- Prolactin
Increased posterior pituitary secretion of:
-ADH (vasopressin)
TSH, LH and FSH may be increased or decreased
What are the key endocrine organs involved in the response to stress?
Pituitary Adrenals Pancreas Kidneys Thyroid Gonads
Outline the adrenal response to stress
Increased:
- Catecholamines
- Cortisol
- Aldosterone
Outline the pancreatic response to stress
Increased:
-Glucagon
Decreased:
-Insulin
Outline the renal response to stress
Increased renin production
Outline the gonadal response to stress
Decreased:
- Testosterone
- Oestrogen
Outline the thyroid’s response to stress
Decreased:
-Tri-iodothyronine
What is the main cytokine associated with the surgical stress response?
What its profile following insult?
IL-6
Levels rise 2-4h after start of surgery and peak between 12-24h.
Amplitude of peak reflects severity of tissue damage
How does IL-6 affect the systemic response to stress?
IL-6 (and IL-1) have been shown to stimulate pituitary secretion and thus the stress response.
Cortisol release has a negative feedback effect on cytokine gene expression
What are the acute phase proteins associated with the stress response?
What is the effect of this production?
Fibrinogen CRP Complement Amyloid P Amyloid A Caeruloplasmin
This results in reduced production of other proteins eg. albumin + transferrin
This results in a reduction in circulating cations eg. Zn, Fe
What are the psychological and behavioural responses associated with surgery?
Anxiety/depression
-Usually brief and self-limiting
Fatigue/malaise
-May last several months
What is known about the physiology of postoperative fatigue?
Little
- Poorly defined/measured
- Not inevitable after major surgery
- Unknown cause and no known treatments
What is known about the psychology of postoperative fatigue?
- May be component of motivational response. For example joint arthroplasty has low rates of post-op fatigue, possibly due to the positive intended effects of surgery whereas abdominal surgery is rarely life-enhancing and has high rates.
- Preoperative fatigue may predict postoperative fatigue
- Association between anxiety/depression and postop fatigue
What surgical/anaesthetic perioperative factors may affect stress response?
- Choice of induction agents
- Volatile agents
- High-dose opioid anaesthesia
- Regional
- NSAIDs
- Minimal access surgery
How does etomidate affect the stress response?
- Inhibits adrenal steroidogenesis
- Acts on mitochondrial 11β-hydroxylase step and 17α-cholesterol cleavage part of the biosynthetic pathway
- May inhibit cortisol and aldosterone porduction for up to 8h post single induction dose
How may benzodiazepines given at induction affect the stress response to surgery?
Diazepam and midazolam inhibit cortisol production in vitro and midazolam has demonstrated this effect in human surgical studies and may have a direct effect on ACTH secretion
What effect do volatile anaesthetic agents have on the stress response to surgery?
Unlikely to have a significant effect on HPA axis - from studies mainly on halothane
What effect does high-dose opioid have on the stress response to surgery?
- Inhibition of HPA axis mediated via the hypothalamus
- Fentanyl 50mcg/kg abolishes cortisol response in pelvic surgery, 100mcg/kg in upper abdo surgery
Discuss the effects of regional anaesthesia on the surgical stress response
- Complete afferent blockade (ie. somatic and autonomic) required for blockade of HPA axis
- Pelvic surgery requires extensive T4-S5 block
- Very difficult to prevent cortisol secretion in upper abdo surgery with reqional techniques
- Limb and eye surgery are amenable to complete blockade
- Regional does not prevent the cytokine response
Outline the evidence relating to spinal/epidural anaesthesia on clinical outcomes
- Evidence of beneficial effects of spinal/epidural anaesthesia on outcomes after major surgery are controversial
- Some evidence does suggest a reduction in DVT and 30-day mortality following hip fracture repair with regional
- Evidence suggests that epidural anaesthesia provides better pain relief and shortens intubation time on ITU following some major abdo surgery eg. aortic surgery
- Significant benefit in reduced occurrence of postop respiratory failure with epidural following major abdo surgery
What effect does NSAID use have on the surgical stress response?
- No effect on HPA axis
- Perioperative diclofenac may show reduced IL-6/10 and WCC response but must be started at least 24h prior to surgery for effect
What effect may endoscopic surgery have on the stress response?
-Endoscopic surgery does not affect the neuroendocrine response to surgery but does reduce the acute phase response and is associated with relatively preserved immune function relative to open techniques
List the possible health risks of obesity
Neuropsychiatric
- Headaches
- Poor sleep
- Depression
- Poor self-esteem
Cardiovacscular
-HTN, IHD, CVA, HF, arrhythmia
GI
- Gallstones
- HH
- NASH -> cirrhosis
Resp
- OSA
- OHS
Metabolic
- T2DM
- Dydlipidaemia
GU
- Infertility, dymenorrhoea, PCOS
- ED
Ortho
- Joint disease
- Mobility impairment
Summarise the pathways governing energy balance
NTS receives two types of signal:
- Adiposity signals:
- From fat mass via leptin and insulin -> arcuate nucleus -> paraventricular nucleus and lateral hypothalamus (neuropeptide Y is stimulatory; Pro-opiomelanocortin is inhibitory) -> anabolic or catabolic signals to NTS - Satiety signals:
- From liver and GIT via autonomic afferents directly to NTS
The integrated response is then transmitted via ANS efferents
What mechanism is implicated in the food reward response?
Insulin acts to reduce dopamine clearance
Summarise the role of leptin in energy balance
- Hormone released from adipose tissue, signalling adipose mass to the CNS
- Increases melanocyte-stimulating hormone and inhibits neuropeptide Y
- Reduces drive for food intake and permits increased energy use via sympathetic stimulation
Summarise the role of insulin in energy balance
- Acts in CNS to increase melanocyte-stimulating hormone and inhibit neuropeptide Y (in a manner similar to leptin)
- Reduces drive for food intake and permits increased energy use via sympathetic stimulation
What is the effect of leptin level on metabolism?
Reduced leptin levels eg. with prolonged starvation, reduces basal metabolic rate, in order to limit weight loss
Which dopamine receptors are implicated in the food reward system?
D2
What role may insulin resistance have on the food reward response?
Insulin resistance in the ventral segmental area may lead to dopamine accumulation in the nucleus accumbens -> enhanced pleasure response to food
What are the main categories of fat distribution?
Android / Gynaecoid
Android:
- Central obesity with peripheral sparing
- Higher cardiovascular risk association
Gynaecoid:
-More peripheral distribution (arms, legs, buttocks)
How does obesity affect lung capacities in anaesthesia?
For BMI >30:
- Reduced FRC
- VC reduced by 40% of baseline in laparotomy
- Compared to reduction of 10% in lean patients
How does rate of absolute energy consumption differ between the obese and non-obese patient?
How does this impact anaesthesia?
Absolute energy requirements (and thus O2 consumption and CO2 production) are increased for the obese patient.
This has implications for low-flow anaesthesia and minute volumes
Elaborate on the possible respiratory consequences of obesity in anaesthesia
- Risk of airway obstruction/collapse
- Possible pre-existing OSA/OHS
- Increased mass of chest wall and IA pressure leads to:
- Reduced FRC and VC
- Increased A-a gradient
- Increased closing capacity
- Increased shunt
What are the diagnostic criteria for obesity hypoventilation syndrome?
- Awake PaCO2 of >6kPa
- BMI > 30
- Absence of other cause of hypercarbia
- OSA present (supportive - 83% of OHS also have OSA)
What are the possible anaesthetic consequences of OSA/OHV?
- Respiratory alkalosis at normocapnia
- Difficult or impossible ventilatory weaning
- Prolonged postoperative respiratory depression
What are some possible anaesthetic techniques to limit the problems associated with obesity?
- Increased PEEP to prevent derecruitment
- Recruitment manoeuvre immediately following induction (when majority of atelectasis occurs)
- Use of CPAP during induction
- Possible reduction in atelectasis if FiO2 of <1.0 used prior to intubation
What are the possible physiological effects of pneumoperitoneum for the obese patient?
- Reduced venous return
- Reduced CO
- Increased PAP
- Increased ICP
- Raised IA pressure and risk of splanchnic ischaemia and surgical emphysema
- Raised PaCO2 -> resp acidosis
- Sympathetic activation -> arrhythmia, increased SVR
What is the effect of obesity on cardiac myocytes?
- Mechanical effect from myocardial adipocytes
- ‘Cross-talk’ with adipocytes reduces fibre-length and peak intracellular calcium
What is the effect of obesity on the vascular endothelium?
- Endothelial dysfunction and increased SVR.
- Possibly through leptin-mediated expression of myocardial endothelin-1
How does muscle blood flow increase from resting to exercise?
Resting: 4ml/100g/min
Exercise: Up to 100ml/100g/min
What is the difference between endurance and resistance training in terms of cardiovascular changes
Main difference is that endurance training increases CO, whereas resistance training has little effect
How much energy does a mole of ATP produce?
7.3 kcal (30.7 kJ)
What are the routes to ATP production relevant to immediate use in exercise?
- Stored ATP
- Phosphocreatine system
- Adenylate kinase reaction:
- ADP + ADP = ATP + AMP
Summarize the sources of ATP production at different durations of exercise
2-20 secs:
-ATP-phosphocreatine system
20 - 45 secs:
-Anaerobic glycolysis
45 s - 10 min:
- Aerobic
- Glycolysis
- Phosphocreatine
10 min+
-Aerobic metabolism, reaching steady state
What is the anaerobic threshold?
aka. lactate threshold. AT is the point at which serum lactate starts to rise significantly with increasing VO2
What are the possible mechanisms for the anaerobic threshold?
- Reduced O2 in muscles
- Accelerated glycolysis
- Recruitment of fast-twitch fibres (which favour lactate production)
- Reduced lactate removal
- Failure of ETC to keep up with glycolysis (excess NAHD in sarcoplasm promotes lactate conversion)
What is the ‘crossover concept’ in exercise?
As exercise increases, relative proportion of carbohydrate : fat use increases due to recruitment of slow-twitch fibres.
The crossover point is around 35% of VO2max
What effect does duration of exercise have on source of energy?
At constant exertion, increasing duration of exercise increases the ratio of fat : carbohydrate metabolism
The crossover point is around 20 mins
Describe and explain the relationship of VO2 with exercise over time
On starting exercise, it takes some time for VO2 to reach steady state. The resultant lag between energy production and O2 consumption implies the contribution of anaerobic metabolism -> O2 deficit.
Following cessation of exercise, it takes some time for VO2 to return to the resting level, this excess of post-exercise O2 consumption is termed O2 debt. It has two main components:
Rapid debt:
-Resynthesis of phosphocreatine and replenishment of O2 ‘stores’
Slow debt:
-Metabolism of lactic acid
Factors such as ongoin ^work of breathing/tachycardia, elevated hormones and hyperthermia also contribute to oxygen debt
What are the factors that contribute to VO2max?
Central / Peripheral:
Central:
- Pulmonary function - usually only relevant at altitude or with pulmonary disease
- Cardiac - Increased CO via SV is important, and likely the limiting factor determining DO2 (and thus VO2max) at maximal exercise
- O2 carrying capacity - Generally does not limit VO2, but VO2max may be increased by increasing CC (eg. EPO abuse)
Peripheral:
- Number of mitochondria in skeletal muscle influences O2 extraction but is not a limiting factor for VO2max
- Increasing muscle capillary density increases O2 extraction and may increase VO2max
What is the maximum efficiency of conversion of energy sources into muscular work?
What are the consequences of this?
20-25%
This means that increased exercise creates excess heat, which must be dissipated to avoid heat exhaustion
