on 20111

1. The Systemic Response toThe Systemic Response to
surgery
BBy
HS. Kyi San Thi
The Surgeon 29:2, February, 2011,T Tatiana Gutierrez

2. OutlineOutline
1 I t d ti1. Introduction
2. The endocrine response to surgery
3. The haemodynamic response to surgery
4. The immune system and the systemic response4. The immune system and the systemic response
to surgery
5 Effects of anaesthesia5. Effects of anaesthesia
6. Systemic response to surgery during specific
dprocedures
6.6.2011 Kyi San Thi 2

3. 1.Introduction
• The response of the body to the
traumatic insult of a surgical procedureg p
has 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

4. • Now it has been recognized that the
systemic response to surgeryy p g y
encompasses a wide range of
interlinked endocrinological , metabolicg ,
and immunological pathways.

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

6. 2.The endocrine response to surgery
• Hormonal response to surgery is
characterized by increased secretion ofy
stress hormones.(adrenaline ,cortisol
are prominent markers)p )
• Also glucagon, growth hormone,
aldosterone ADHaldosterone, ADH

7. • In response to surgery, not only
hormonal pathways but alsop y
sympathetic nervous system lead to
catabolism with mobilization ofcatabolism, with mobilization of
substrates – to provide energy, salt and
water retention cardiovascularwater retention,cardiovascular
haemostasis.

8. Hormonal response by
• The sympatho-adrenal response
• The hypothalamo – pituitary – adrenal
axisaxis

9. 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.

10. The hypothalamo-pituitary-adrenal axis
Site of injury
Afferent impulses
Hypothalamus
Rreleasing factors
Pituitary
adrenal

11. ACTH and cortisol
• ACTH is formed in pituitary from the
metabolism of the larger molecule, pro-g , p
opiomenlanocortin.
• ACTH stimulates glucocorticoidsACTH stimulates glucocorticoids
release from adrenal cortex.
• Surgery is the most potent activators of• Surgery is the most potent activators of
ACTH and cortisol secretion. *

12. • Cortisol has complex metabolic effects
on carbohydrates : glucose used byy g y
cells is inhibited → glucose ↑
• Fat - ▲ lipolysis → FFA ↑Fat ▲ lipolysis → FFA ↑
• And protein - ↑ catabolism
Al h i i ti• Also have permissive actions
on catecholamines and glucagon.

13. 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.

14. 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.

15. 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

16. Gonadotrophins (LH and FSH)
• Significant in response to surgery is
unknown.
• But testosterone level is decreased
several days following surgeryseveral days following surgery.

17. 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 g
insulin secretion does not match the
catabolic response,leading to net
catabolism

18. 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.

19. ADH
• ADH is produced from posterior
pituitary.p y
• Increased during surgery.

20. Metabolic sequelae of the endocrine response
• The net effect of the endocrine
response to surgery - ↑catabolicp g y
hormones → 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.

21. • The ability to recover following surgery
may be dependent on the ability toy p y
deliver the increased oxygen demand to
tissues during the hypermetabolicg yp
phase.
• Catabolism may result in marked weightCatabolism may result in marked weight
loss and muscle wasting in patients
after surgeryafter surgery.

22. Hormonal changes in response to surgery
Hormonal
change
Pituitary Adrenal cortex Pancreas Thyroid
↑ ACTH Cortisol Glucagon
ADH
GH
Aldosterone
Catecholamine
g
↔ FSH
LHLH
↓ TSH Insulin T3
T4

23. 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 →Angiotensin
II→Aldosterone→salt and water retention

24. 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 preventp
postoperative 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.

25. For first 36 hours
P i fl tPro inflammatory response
SIRS
Sepsis
Anti-inflmmatory response

26. • If Pro inflammatory response ↑↑↑ or
Anti – inflammatory response ↓↓ , SIRS
may result.
• In patient with significant copat e t t s g ca t co
morbidities, the immune system may
become exhausted, leading tobeco e e aus ed, ead g o
immunoparalysis and a predominant
anti – inflammatory response,y p ,
predisposing to postoperative infection.

27. Specific immune response (cytokines)*
• A barrage of pro-inflammatory cytokines is
released by monocytes at the site of tisssue
damage , 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.

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

29. • 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..

30. 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.

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

32. 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 andwith the production of cortisol and
aldosterone. (↑mortality when used in
critically ill case)critically ill case)

33. ♪ 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 ofcan block afferent input from the site of
surgery to H-P axis and efferent ANS
pathwayspathways.

34. 5.Systemic response to surgery during
specific procedures
• Intra abdominal surgery
Concentrations of norepinephrine ACTHConcentrations of norepinephrine, ACTH,
CRP and IL6 are lower following laproscopic
gastric bypass compared to open gastricg yp p p g
bypass, implying a lower degree of operative
injury.

35. 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 fblood
with artificial surfaces in the extracorporeal circulation
and pumps.

36. 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.

37. 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 generalizedg
physiological response.
• The systemic response to surgeryy 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.