journal reading in surgical posting : the systemic response to surgery

The Systemic Response toThe Systemic Response to surgery

BByHS. Kyi San Thi

The Surgeon 29:2, February, 2011,T Tatiana Gutierrez

OutlineOutline1 I t d ti1. Introduction2. The endocrine response to surgery3. The haemodynamic response to surgery4. The immune system and the systemic response4. The immune system and the systemic response

to surgery5 Effects of anaesthesia5. Effects of anaesthesia6. Systemic response to surgery during specific

dprocedures6.6.2011 Kyi San Thi 2

1.Introduction

• The response of the body to the traumatic insult of a surgical procedure g phas been of interest to scientists for many years.y y

• In 1932, Cuthbertson describe physiological response to trauma usingphysiological response to trauma using the terms ebb and flow.

25.1.2011 Kyi San Thi 3

• Now it has been recognized that the systemic response to surgery y p g yencompasses a wide range of interlinked endocrinological , metabolic g ,and immunological pathways.

• Surgery like any other infectious or non-infectious insult, may lead to the systemic inflammatory response syndrome.

ARDS

MOFSIRS

Sepsis

2.The endocrine response to surgery

• Hormonal response to surgery is characterized by increased secretion of ystress hormones.(adrenaline ,cortisolare prominent markers)p )

• Also glucagon, growth hormone, aldosterone ADHaldosterone, ADH

• In response to surgery, not only hormonal pathways but also p ysympathetic nervous system lead to catabolism with mobilization ofcatabolism, with mobilization of substrates – to provide energy, salt and water retention cardiovascularwater retention,cardiovascularhaemostasis.

Hormonal response by

• The sympatho-adrenal response

• The hypothalamo – pituitary – adrenal axisaxis

The sympatho adrenal axis

• During surgery, sympathetic autonomic nervous system is activated.y

• This results in increased secretion of catecholamines from adrenal medullacatecholamines from adrenal medulla.

• Increased activity leads to tachycardia and hypertensionand hypertension.

The hypothalamo-pituitary-adrenal axis

Site of injury

Afferent impulses

Hypothalamus

Rreleasing factors

Pituitary

adrenal

ACTH and cortisol

• ACTH is formed in pituitary from the metabolism of the larger molecule, pro-g , popiomenlanocortin.

• ACTH stimulates glucocorticoidsACTH stimulates glucocorticoidsrelease from adrenal cortex.

• Surgery is the most potent activators of• Surgery is the most potent activators of ACTH and cortisol secretion. *

• Cortisol has complex metabolic effects on carbohydrates : glucose used by y g ycells is inhibited → glucose ↑

• Fat - ▲ lipolysis → FFA ↑Fat ▲ lipolysis → FFA ↑• And protein - ↑ catabolism

Al h i i ti• Also have permissive actionson catecholamines and glucagon.

Growth hormone (GH)♥ a peptide secreted from ant: pit♥ In addition to regulation of growth, g g ,

it has multiple effects on metabolism.♥ The secretion of growth hormone from♥ The secretion of growth hormone from

ant: pit increase in response to surgery and traumaand trauma

♥ It is correlated to severity of the injury.

Beta-endorphin and prolactin♥ β endorphin –an opioid peptide from♥ β endorphin an opioid peptide from

ant: pit: but no major metabolic pathway♥ Prolactin from anterior pituitary is♥ Prolactin from anterior pituitary is

increased as part of the stress response to surgery but its exact purpose isto surgery, but its exact purpose is unknown.

Thyroid hormone

TSH Anterior pituitary↓

Due to surgery,cortisol level increased

T3 , T4 Thyroid gland

cortisol level increased

↓

Stimulate oxygen consumption of tissues and increase the sensitivity of heart to the action of catecholamines and increasing the affinity and

number of cardiac beta adrenoreceptors

Gonadotrophins (LH and FSH)

• Significant in response to surgery is unknown.

• But testosterone level is decreased several days following surgeryseveral days following surgery.

Insulin• Insulin is the key anabolic hormone.• It is polypeptide with 2 chains linked by• It is polypeptide with 2 chains linked by

2 disulphide bonds.I li ▼ t i t b li li l i• Insulin - ▼ protein catabolism, lipolysis,

• - hypoglycemic action• After induction of anaesthesia, insulin

levels may decrease and during surgery, g ginsulin secretion does not match the catabolic response,leading to net catabolism

Glucagon

• It promotes hepatic glycogenolysis, gluconeogenesis and lipolysis .g g p y

• During surgery, plasma glucagon level increasedincreased.

• Not a major contribution to the hyperglycaemic responsehyperglycaemic response.

ADH

• ADH is produced from posterior pituitary.p y

• Increased during surgery.

Metabolic sequelae of the endocrine response

• The net effect of the endocrine response to surgery - ↑catabolic p g yhormones → breakdown of skeletal muscles and fat and ↑gluconeogenesis and insulin resistance manifested as hyperglycaemia.yp g y

• It was correlated to the intensity of the surgical insultsurgical insult.

• The ability to recover following surgery may be dependent on the ability to y p ydeliver the increased oxygen demand to tissues during the hypermetabolicg ypphase.

• Catabolism may result in marked weightCatabolism may result in marked weight loss and muscle wasting in patients after surgeryafter surgery.

Hormonal changes in response to surgery

Hormonal change

Pituitary Adrenal cortex Pancreas Thyroid

↑ ACTH Cortisol GlucagonADHGH

AldosteroneCatecholamine

g

↔ FSHLHLH

↓ TSH Insulin T3T4

2.The haemodynamic response to surgery

• Fluid lost in surgery (blood or body fluids)+ hormonal changes influences salt and water retention and production of concentratedretention and production of concentrated urine by direct action of the kidney.

• ↑ sympathetic efferent stimulation in the kidney → renin from JG cells →Angiotensinkidney → renin from JG cells →AngiotensinII→Aldosterone→salt and water retention

3 The immune system and the systemic3.The immune system and the systemic response to surgery

• A functioning immune system is essential in order to prevent ppostoperative complications , particularly sepsis.p y p

• However, surgery insigates a number of response from both the specific and nonresponse from both the specific and non specific immune systems, both pro and anti inflammatoryanti inflammatory.

For first 36 hours

P i fl tPro inflammatory response

SIRS Sepsis

Anti-inflmmatory response

• If Pro inflammatory response ↑↑↑ or Anti – inflammatory response ↓↓ , SIRS may result.

• In patient with significant co pat e t t s g ca t comorbidities, the immune system may become exhausted, leading to beco e e aus ed, ead g oimmunoparalysis and a predominant anti – inflammatory response, y p ,predisposing to postoperative infection.

Specific immune response (cytokines)*

• A barrage of pro-inflammatory cytokines is released by monocytes at the site of tisssuedamage , including IL1,IL6 and TNF .

• IL6 stimulates the synthesis of hepatic acute h t i h CRP C 3phase proteins, such as CRP, C 3

complement ,etc.Th l t t i ti t d hi h i• The complement system is activated, which is closed connected to the coagulation cascade.

• The degree of tissue damage and duration of surgery correlate with the g ylevels of IL6 released, which in term has been shown to correlate the risk of postoperative complications.

• IL-6▲ anti –inflammatory cytokines (IL-10 IL-1receptor antagonist) (IL 10, IL 1receptor antagonist)

S th i iti l i fl t• So the initial pro-inflammatory response is usually balanced by the

t ti i fl tcompensatory anti-inflammatory response..

Non Specific immune system responseNon Specific immune system response (cell mediated)

• It is mediated by Neutrophils, monocytes and natural killer (NK) cells, and may suppressed by surgical trauma.

• Surgery → accumulation of macrophages and granulocytes in traumatized tissue and peripheral leucocytosis.Alth h l t i iti ll l t t • Although granulocytes initially accumulate at the site of injury, they have reduced ability after initial pro-inflammatory responseinitial pro-inflammatory response.

• Monocytes are less able to present Ag on their surface, for up to a week after , psurgery.

• The activity of NK cells is alsoThe activity of NK cells is also suppressed ,

• NK cells act as a defense against• NK cells act as a defense against metastasis.I t t i ti t ith li• Important in patient with malignancy

4 Effects of anesthesia on the systemic4.Effects of anesthesia on the systemic response to surgery

• Drugs used in anesthesia can alter the systemic response to surgery. y p g y

♪ Opioid analgesia : ▼ Hypothalamus and pituitary hormone secretionand pituitary hormone secretion.

♪ Induction agent , etomidate : can interfere with the production of cortisol and with the production of cortisol and aldosterone. (↑mortality when used in critically ill case)critically ill case)

♪ Benzodiazepines: ▼ cortisol production but clinical significance is unknown.g

♪ Antihypertensive clonidine (alpha2 agonist) ▼sympathetic pathwayagonist) ▼sympathetic pathway.

♪ Regional anaesthesia (epidural block) can block afferent input from the site of can block afferent input from the site of surgery to H-P axis and efferent ANS pathwayspathways.

5.Systemic response to surgery during specific procedures

• Intra abdominal surgeryConcentrations of norepinephrine ACTHConcentrations of norepinephrine, ACTH, CRP and IL6 are lower following laproscopicgastric bypass compared to open gastric g yp p p gbypass, implying a lower degree of operative injury.

Cardiovascular surgery

• In vascular surgery, such as abdominal aortic aneurysm repair, intraoperative ischaemia and then reperfusion may occur in dependent tissuesreperfusion may occur in dependent tissues.

• During reperfusion, SIRS may elicited.• Cardiopulmonary bypass may induce a severeCardiopulmonary bypass may induce a severe

systemic inflammatory response, including activation of the complement and coagulation cascades and possible DIC (triggered by contact activation o fbloodpossible DIC. (triggered by contact activation o fbloodwith artificial surfaces in the extracorporeal circulation and pumps.

Orthopaedic Surgery

• PMMA (bone cement) cause hypotension, bradycardia, and even cardiac arrest.

• Pathogenic mechanisms have been proposed by several theories : pulmonary embolism

d b ti d b i bcaused by tissue debris or bone marrow expelled from the medullary cavity; a neurogenic reflex or a direct toxic orneurogenic reflex , or a direct toxic or vasodilator effect of the cement.

Conclusion• The local effects of surgery on tissue andThe local effects of surgery on tissue and

organ systems are usually evident.• The trauma of Sx itself leads to a generalized g

physiological response.• The systemic response to surgery y p g y

encompasses a wide range of interlinked endocrinological, metabolic and i l i l himmunological pathways.

• Although some of these mechanisms can be t ti th t i tprotective, the systemic response to surgery

can lead to SIRS.