Neuro Hormonal Response to Injury

7/17/2019 Neuro Hormonal Response to Injury

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Presented by: Dr. Rafiq M. Salhab.

Alahli Hospital, Hebron.

3/10/01!

رح ل ا ن محر ل ا ا سب

Al"#$ds %ni&ersity

'a($lty of Medi(ine

Neuro-hormonal response to injury



Response to injury

Integrated series of endocrine and metabolic changes to maintain homeostasis

and glucose and oxygen delivery to vital organs and tissues.

The response is initiated by loss of effective circulatory volume and pain.

The most important stimulus is the afferent sensory nerve from the injured

area.

Other stimuli are: hypoxemia hypercarbia acidosis exotoxins endotoxins

emotional stress inflammatory cells and local tissue damage !burns surgery".



Response to injury

#any organs and systems participate in this response: hypothalamus pituitarygland heart major vessels !carotid sinus" chemoreceptors !carotid bodies"

$idney adrenals% ecc.

Increased levels of: &R' (&T) (*+ &atecholamine corticosteroids

glucagon ,) (ldosterone cyto$ines I TN' eicosanoids leu$otrienes NOendothelins and prostaglandin. Table !"

/ndocrine !Neuro-hormonal" . Table !0"

#etabolic

Immune



Neuro-hormonal ! /ndocrine " response to injury:

)able*1+ Systei( response to in-$ry

1ympathetic nervous system activation

/ndocrine stress response

- pituitary hormone secretion - insulin resistance

Immunological and hematological changes

- cyto$ines production

- acute phase reaction - neutrophil leu$ocytosis - lymphocyte proliferation



ndo(rine land horones hane in se(retion

(nterior pituitary (&T),)T1)

'1) and )

IncreasesIncreases

#ay increase or decrease#ay increase or decrease

+osterior pituitary (*+ !(2)" Increases

(drenal cortex &ortisol(ldosterone

Increases Increases

+ancreas Insulin,lucagon

Often decreases3sually small increases

Thyroid Thyroxin tri-iodothyronine 2ecrease

Table !0" principal hormonal responses to injury



Sypathoadrenal response: a(ti&ated by the hypothala$s.

ate(holaines: or"epinephrine and epinephrine.

" or"epinephrine is released fro sypatheti( postanlioni( ne$rons.

" pinephrine is se(reted by the adrenal ed$lla *lo(al and distant a(tions+.

2ifferent types of receptors !4 40 5 50 ".

(fter injury levels rise immediately and pea$ 6ithin 07-78 hours

!psychological component fight or flight response to danger or pain"

Their actions are primarily metabolic and hemodynamic. - )yperglycemia: glycogenolysis9 glucagon insulin.

- )emodynamic effects: vasoconstriction!4 " arterial vasodilatation ! 50"9 )R

9 conductivity 9 contractility!5".

The effects are dose-dependent:

- o6-dose ; 5 50 .

- )igh-dose ; 4 40 .



)he hypothalai("pit$itary"adrenal a2is: )able *+ fi$re 1

+ain and hypovolemia are the primary stimuli .

The response is proportional to the magnitude of the volume loss.

#aximum response is achieved 6hen the volume is decreased by <=-7=>.

Rapid losses are not as 6ell tolerated as slo6 losses.

Hypothala$s: hypothalamic releasing factors stimulating the pituitary gland.

Anterior pit$itary *adeno"hypophysis+:

1. A)H: in response to &R) from hypothalamus.

- stored as a large molecule +O#& !pro-opiomelanocortin".

- acts on ?ona fasciculata of adrenal cortex to produce &ortisol and (ldosterone from ?onaglomerulosa.

- ortisol has negative feedbac$ on (&T) secretion !6hich is inhibited during se@uential

injury severe hypovolemia and &ushing disease".

ortisol: ha complex activity on carbohydrate fat and protein.

-proteolysis and gluconeogenesis in the liver.

-inhibition of glucose upta$e by cells.

-lipolysis ; glucose.

-anti inflammatory activity: +hosphorylase A , cyto$ines neutrophils and macrophages in

inflammation ?one.

-inhibits conversion of T7 to T<



Figure 1 Hypothalamic-pituitary-adrenal-axis



Aldosterone:

-Renin-angiotensin system.

-increased resorption of Na and &l A excretion. " 9 production of (*+.

. ro4th horone *H+:HR'

"insulin-li$e gro6th factor!I,'- and I,'0".1omatomedins !from the liver".

-the main action during stress is to promote protein synthesis.

-lipolysis ; hyperglycemia.

-carbohydrates brea$do6n !glycogenolysis"; hyperglycemia.

-inhibition of glucose upta$e.

<. T1):

- is decreased during stress because of &ortisol effect B ; decreased T< ;decreased metabolic rate and oxygen consumption.

- exogenous steroids suppress T<.



5. 'SH and 6H

-Their secretion is suppressed after injury: decreased testosterone and estrogen.

-#enstrual dysfunction. -decreased libido.

!. Prola(tin:

The importance of its action follo6ing injury is not 6ell $no6n.

. 7"ndorphin: endoeno$s opioid.

- 9 concentrations in circulation after injury reflect pituitary hormone secretion.

- associated 6ith hyperglycemia.

- some opioid peptides have the ability to suppress immunologic function. - analgesic effect.

- their precise action still under investigation.



Posterior pit$itary *e$ro"hypophysis+:

A8P *ADH+:

-is synthesi?ed in the hypothalamus and stored in the Neurohypophysis. -stimulated by increased plasma osmolality (&T) (ngiotensin II &ortisol

pain and &atecholamines.

-its action:

osmo-regulatory: resorption of solute-free 6ater.

vasoactive: peripheral vasoconstriction !splanchnic bed".

metabolic: hepatic glycogenolysis and gluconeogenesis.

Head in-$ry (an (a$se:

-1I(2) -2iabetes insipidus.



6o(al tiss$e daae ediators: (yto9ines +roduced de novo locally at site of injury by activated leu$ocytes fibroblasts and

endothelial cells as an early response.

They include Interleu$ins !I" Interferons eicosanoids and endothelial cell factors.

#ajor role in mediating immunity and inflammation.

&ell-to-cell !paracrine" and distant !hormonal" functions.

&yto$ines that affect immune function are termed lympho$ines and include: I

TN' !tissue necrosis factor" and the Interferons.

(fter major injury the main cyto$ines released are I- TN'-4

and I-C and they

promote the synthesis of hepatic acute Dphase proteins.

Regional anaesthesia 6ith local anaesthetic agents inhibits the stress response to

surgery and can produce a beneficial effects on organ function post-operatively.

6"1:

- 9 T cell proliferation.

- fever.

- anorexia.

- deceased pain.

- brea$do6n of s$eletal muscle.

- hyperglycemia by suppression of insulin secretion.



)' *a(he(tin+:

1timulated by complement activation

+roduced by monocytes macrophages Aupffer cells mast cells andendothelial cells.

)' ; 6"1: hypotension tissue necrosis cell death release of prostaglandin

cytotoxic for islet cells.

)' ; 6": eicosanoids and platelet-activating factor. )ypotension in sepsis.

6"<: " 9 <=-C= min after injury and significant after 0-7 h.

" 9 is proportional to the degree if insult.

- enhance immune function and hepatic protein synthesis.

- promote the synthesis of hepatic acute Dphase proteins.

nterferon =: ly(oprotein prod$(ed by lypho(ytes ).

- activates macrophages to release I- and TN'.

- 9monocytes I-0 expression.

- inhibits viral replication.

- inhibits +,/0 reducing the immuno-suppression effect of +,/0 .



i(osanoids: the fat ediators of sho(9. 'i$re

2erived from arachidonic acid in response to hypoxia ischemia injury

fibrinogens endotoxin nor-epinephrine (*+ angiotensin II brady$ininserotonin and histamine.

+rostaglandins thromboxane and leu$otrienes !COX, thomb.synth,LOX)

Their effects depend on 6hat stimulates their production and 6hat cells

produce them for example:

- +rostacycline !+,I0" produced by vascular endothelial cells: vasodilatation. - thromboxane ( 0 !Tx(0" causes vasoconstriction and platelet aggregation.

- leu$otrienes including slo6-releasing substance of anaphylaxis: they produce

capillary lea$age bronchospasm and vasoconstriction.

+rostaglandins are the major component of inflammatory response.

(R21 pancreatitis and some forms of renal failure !caused by

/icosanoids B".



Figure 2



ntera(tion bet4een the $ne syste and the e$ro"endo(rine syste:

- I- (nd I-C can stimulate secretion of (&T).

- the &ortisol response to surgery is sufficient to depress I-C concentration.



Metaboli( response to in-$ry:

(ctivation of stress hypermetabolism follo6ing surgery trauma or sepsis.

Resistant hyperglycemia to provide energy and substrate for tissue repair andto activate immune function and the inflammatory response.

Increased levels of: &R' (&T) (*+ &atecholamine corticosteroids

glucagon ,).

2ecreased or normal Insulin level 6ith peripheral resistance to insulin.

)yperglycemia: glycogenolysis gluconeogenesis reduced peripheral cell

utili?ation of glucose.

Increased use of protein as fuel leading to hypoalbuminemia and decreased

muscle mass.



Metaboli( response to in-$ry (ontin$e:

)4o phases of response:

1. bb phase !07-<C hours". 2ecompensation O0 consumption fluid

imbalance and cellular shoc$.

. 'lo4 phase !can last days 6ee$s or months". body adaptation: 9cellular

activity 9 hormonal stimulation 9metabolic rate 9body temperature 9 Nloss in response to stress hormonal and inflammatory mediators.

A.Catabolic: 9gluconeogenesis 9R// 9proteolysis ureagenesis 9 urine N loss.

!clinically: tachypnea fever tachycardia lab: leu$ocytosis hyperlactatemia

a?otemia and hyperglycemia".

B.Anabolic: weight gain and positive N balance.



Metaboli( seq$elae of the endo(rine response:

increased secretion of catabolic hormones as a survival mechanism using stored

body fuels and retaining salt and 6ater giving the body a chance to survive

6ithout food until healing and repair had ta$en place. arbohydrate etabolis:

- increased blood levels of glucose

- increased glycogenolysis.

- increased gluconeogenesis.

- peripheral insulin resistance. Protein etabolis:

- s$eletal muscle is bro$en do6n amino acids are used as energy and substrate.

- mar$ed 6eight lost and muscle 6asting.

- increased Nitrogen secretion in the urine.

'at etabolis:

- lipolysis of T, to glycerol and fatty acids.

- glycerol is used for gluconeogenesis in the liver.

- fatty acids are converted to $etone bodies or re-esterified in the liver and

muscles.

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Neuro Hormonal Response to Injury