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Oxidative Stress in
Necrot=
izing
Enterocolitis
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Goals & Objectives
=
=
§Discuss etiology & diagnosis of <=
span
style=3D'position:absolute;top:32.75%;left:15.54%;width:78.65%;height:6.5%=
'>Necrotizing enterocolitis (NEC)
<=
/div>
§Describe
clinical presentation & surgical
management of NEC
§Discuss the role of oxidative stress in injures intestine, molecular signaling mechanisms involved in NEC
Necrotizing Enterocolitis(NEC)
=
=
§Most
common GI emergency in neonates
§Prematurity is the single most important risk factor
§Well-described risk factors: ischemia, bacteria, cytokines, enteral feeding
§Exogenous
surfactant & mechanical ventilation contribute to greater numbers of premature infants at risk for developing NEC
§Significant
morbidity and mortality
§Exact
etiology remains poorly understood
§Animal
models are not reliable
§Cellular mechanisms involved in NEC <=
span
style=3D'position:absolute;top:86.25%;left:11.42%;width:58.61%;height:4.75=
%'>remain undefined
![](3D"slide0002_image013.gif")
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Necrotizing Enterocolitis (NEC)
=
§Most commonly affects terminal ileum and proximal =
§Varying degrees of NEC can affect any =
segment of the small intestine or colon
§Pattern of disease: =
single isolated area or multiple, diffuse =
lesions
![](3D"slide0016_image015.gif")
Terminal
<=
span
style=3D'mso-spacerun:yes'> ileum
Ileocecal
valve
Necrotizing Enterocolitis (NEC)
=
=
§=
;Incidence:
§=
;0.3-2.4 : 1000 live births; ♂=3D♀
*=
Breastfed infants have a lower incidenc=
e of NEC than formula-fed infants
§=
;
§=
;Mortality & Morbidity:
§=
; 1000g 40
-100%
§=
;
<1500g 10 - 44%=
3;
§=
;
>2500g 0 -
20%
Clinical Presentation
=
=
§The development of NEC usually occurs after =
1 week of life
§Clinical presentation of NEC: nonspecific & unpredictable
§Clinical signs: irritability, temperature instability, poor feeding, episodes of apnea or bradycardia
§More specific signs: abdominal distention, <=
/span>vomiting, feeding intolerance, or passage of bloody stools
§NEC progression: systemic sepsis, cardiorespiratory deterioration, coagulopathy, and death
§
![](3D"slide0017_image018.gif")
Symptoms of NEC
<=
span
style=3D'font-family:Verdana;font-size:123%'>§Initial:
Feeding intolerance
Delayed Gastric Emptying
Decreased
bowel sounds and inactivity,
bloody stool
<=
span
style=3D'font-family:Verdana;font-size:123%'>§Systemic:
Apnea
Lethargy
Decreased peripheral perfusion
Shock
Cardiovascular Collapse
Consumption Coagulopathy
![](3D"slide0025_image020.gif")
Radiographic findings
=
=
=
§=
Radiographic
hallmark – pneum=
atosis
intestinalis
§=
Pneumatosis
: hydrogen gas generated
by bacterial fermentation of luminal substrates
§=
Other
findings: portal venous=
=
gas, ascites, fixed loops of =
SB, or free air
Histology of NEC
Histologic grading:
0 Nor=
mal,
no damage
+1 Slight submucosal/ lamina <=
/span>propria separation
+2 Moderate separation of submucosa/ lamina propria ± edema in submucosa and muscular layers
+3 Severe separation of submucosa/ lamina propria ± severe edema in submucosa and muscular layers, region of villous <=
span
style=3D'position:absolute;top:73.0%;left:10.11%;width:46.44%;height:4.75%=
'>sloughing
+4
Loss of villi with necrosis
=
NEC
![](3D"slide0020_image022.gif")
Coagulative
necrosis
Loss of villi &
necrosis=
Separation of submucosa
Mucosa
Submucosa
Muscular
layers
Conservative management
=
=
§=
Initial management: bowel rest with NGT decompressi=
on, fluid resuscitation, PRBC & platelet transfusio=
n,
broad-spectrum IV
antibiotics
<=
span
style=3D'font-family:Verdana;font-size:67%;visibility:hidden'>§
<=
span
style=3D'font-family:Verdana;font-size:67%'>§Duration of treatment 7-10 days (50% success rate)&=
#13;
<=
span
style=3D'font-family:Verdana;font-size:67%;visibility:hidden'>§
§<=
/span>Absolute indication for operative management of NEC
– intestinal perforation
(free air on AXR)
<=
span
style=3D'font-family:Verdana;font-size:67%;visibility:hidden'>§
<=
span
style=3D'font-family:Verdana;font-size:67%'>§Relative indications for surgery:
-overa=
ll
clinical deterioration
-abdom=
inal
wall cellulitis
-worse=
ning
acidosis
-leuko=
cytopenia/thrombocytopenia
-palpa=
ble
abdominal mass
-persi=
stent
fixed loop on repeated AXR
§=
Surgery v. risks of laparotomy in an already
compromised premature infant
=
Surgical management
=
=
=
§=
Surgical
management: resection of all nonviable/necrotic segments with crea=
tion
of a stoma
§Preservation of
intestinal length
§=
In
cases of ischemic but not necrotic bowel – a second-look
operation may be performed after 24h
§=
Bowel
resection with primary anastomosis is rare in infants with focal
involvement of NEC and minimal peritoneal contamination a=
nd
hemodynamically stable intra-op; high risk of anastomotic leak =
and =
stricture
formation
§
Surgical management
=
=
§Another
approach : bedside placement of peritoneal
drains under local anesthesia
=
§Drainage =
of the
contaminated peritoneal fluid may
improve ventilation, stop progression of sepsis in select very ill preterm infants
§Multicent=
er,
randomized prospective clinical trial established peritoneal drainage as an accepted mode of treatment for NEC; specifically, survival,=
need for parenteral nutrition, and length of hospital stay were similar for NEC infants =
weighing <1500g treated by either peritoneal drainage or laparotomy - Moss RL, et al, NEJM, 2006
Clinical Impact of NEC
=
=
Intestinal
strictures develop after either medical or surgical
management of NEC in about 10% infants (ABSITE 2008)
=
Long-term morbidit=
ies
for NEC survivors:
Colostomy
=
Repeated surgical
procedures
Short gut
syndrome
Malabsorption
syndrome
Failure to thrive
Intestinal Transplantation =
for
short gut
syndrome
Neurodevelopmental delay
Breast Milk
=
=
<=
span
style=3D'font-family:Verdana;font-size:93%'>§Growth and development
<=
span
style=3D'font-family:Verdana;font-size:93%'>§Immune protection
§=
Insulin-like Growth Factor-1 (IGF-1) & <=
/span>Epidermal Growth Factor (EGF)
§=
Lower incidence of NEC in breastfed v. formula-fed infants Lucas,1990; Eyal,1982
<=
span
style=3D'font-size:80%;visibility:hidden'>§
Oxidative Stress
=
§The most important predisposing factor is Prema=
turity
§Hypoxic stress
§Generation of Reactive oxygen species (ROS) as a result of hypoxic/ ischemic insult
§Inflammatory response
Oxidative stress
& cellular signaling pathways during NEC
![3D"C:\Users\Naira\Desktop\Research](3D"slide0014_image024.jpg")
![3D"C:\Users\Naira\Desktop\Research](3D"slide0014_image026.jpg")