Hepatic and Intestine response to trauma
Yudha Dwi Prasetyo
Medy Ariyatmo
Wayan Baskara
Timotius Wira
Katarina Kala Tandung
Nathanael Denny Sugihat
Wildan Ahmad Furqon
Muftihat Israr
Wilson Wijaya

Introduction
Trauma is still the most common cause of death in children and young adults, as
well as one of the global leading causes of worldwide mortality
Wagner, Nils, et al. "Ethyl pyruvate ameliorates hepatic injury following blunt chest trauma and hemorrhagic shock by reducing local
inflammation, NF-kappaB activation and HMGB1 release." PloS one 13.2 (2018): e0192171.
The treatment of patients with severe and multiple traumatic injuries including
blunt chest trauma and hemorrhagic shock is still challenging

Introduction
Abdominal trauma is an injury to the organs in the abdomen, such as
the stomach, intestines, pancreas, liver, bile, kidneys and spleen.
Wagner, Nils, et al. "Ethyl pyruvate ameliorates hepatic injury following blunt chest trauma and hemorrhagic shock by reducing local
inflammation, NF-kappaB activation and HMGB1 release." PloS one 13.2 (2018): e0192171.
This trauma can occur as a result of a blow or blunt impact, or a sharp object
puncture. Abdominal trauma caused by blunt force is a common presentation in the
emergency room seen in adults and children.

Pathophysiology Abdominal Trauma
Direct impact to intra-
abdominal organs
between walls
anterior and posterior
abdomen
Evrimler, Sehnaz, Irfan Okumuser, and Deniz Delibas. "Delayed small bowel perforation with findings of severe ischemia following blunt
abdominal trauma." Polish journal of radiology 82 (2017): 271.
Avulsion injury caused by the
deceleration force in a high speed
accident or a fall from a height
External compression force
that causes increased pressure
Intraabdomen usually results in
injury to the perforated organ
Intra-abdominal organ laceration
caused by bone fragments

Trauma elicits a series of rapid innate immune responses in an attempt to clear damaged tissues, that is
followed by the activation of repair mechanisms, with the ultimate goal of restoring cells and tissues to
their pre-injury state

Any injury instantly elicits a global stress reaction involving the ANS49,50 that modulates not only
innate immune responses but also organ function and hemodynamics

Hepatic and Intestine role in trauma

Purinergic signaling hypothesis
Purinergic signaling modulates systemic and local inflammatory responses
Ectonucleotidases, ENTPD1 / CD39 and CD73, control of several inflammatory
conditions, ranging from infectious disease, organ fibrosis to oncogenesis
CD39 and CD73 serve as pivotal regulators of intestinal and hepatic inflammation
Vuerich, Marta, Simon C. Robson, and Maria Serena Longhi. "Ectonucleotidases in intestinal and hepatic inflammation." Frontiers in immunology 10
(2019): 507.

Purinergic signaling hypothesis
Extracellular nucleotides, including eATP, promote inflammation, at least in part via
the inflammasome upon engagement of P2 purinergic receptors. In contrast,
adenosine generated during eATP phosphohydrolysis by ectonucleotidases,
triggers immunosuppressive/anti-inflammatory pathways.
Vuerich, Marta, Simon C. Robson, and Maria Serena Longhi. "Ectonucleotidases in intestinal and hepatic inflammation." Frontiers in immunology 10
(2019): 507.

Purinergic signaling hypothesis
Vuerich, Marta, Simon C. Robson, and Maria Serena Longhi. "Ectonucleotidases in intestinal and hepatic inflammation." Frontiers in immunology 10 (2019): 507.
cto-nucleoside triphosphate
diphosphohydrolases
Ecto-5′-nucleotidase
(NT5E)/CD73
Ecto-nucleotide pyrophosphate
phosphodiesterases
CD38/NADase; NAD
glycohydrolases
Adenylate kinases
Ectonucleotidases

Purinergic signaling hypothesis
NT5E/CD73, converts AMP into adenosine, described both as GPI-anchored protein
or soluble enzyme. Soluble CD73 (sCD73) mainly derives from shedding of
lymphocytes and is present in both serum and cell-free lymph of healthy
individual. Increase in sCD73 levels has been reported in inflammatory conditions
Vuerich, Marta, Simon C. Robson, and Maria Serena Longhi. "Ectonucleotidases in intestinal and hepatic inflammation." Frontiers in immunology 10
(2019): 507.

Purinergic signaling hypothesis
ENTPD1/CD39 and NT5E/CD73 can be further induced upon exposure to
oxidative stress and hypoxia, stimulation with pro-inflammatory cytokines or
following aryl hydrocarbon receptor (AhR) engagement
Vuerich, Marta, Simon C. Robson, and Maria Serena Longhi. "Ectonucleotidases in intestinal and hepatic inflammation." Frontiers in immunology 10
(2019): 507.

Ethyl Pyruvate
Wagner, Nils, et al. "Ethyl pyruvate ameliorates hepatic injury following blunt chest trauma and hemorrhagic shock by reducing local
inflammation, NF-kappaB activation and HMGB1 release." PloS one 13.2 (2018): e0192171.
Ethyl pyruvate (EP), has exerted
inflammation-suppressing characteristics
EP reduced the serum myeloperoxidase,
tumor necrosis factor alpha and the damage
lung tissue of ruptured abdominal aortic
aneurysm
Improved the neurological outcome by
reducing inflammation via IL-1β and TNF-α,
as well as microglia activation in brain injury
Reduced alanine aminotransferase (ALT),
aspartate aminotransferase (AST), and IL-6
hepatic ischemia-reperfusion injury

Hepatic System
Liver Kupffer cells control the influx of neutrophils into remote sites
of injury
Al-Tarrah, K., N. Moiemen, and J. M. Lord. "The influence of sex steroid hormones on the response to trauma and burn injury." Burns &
trauma 5.1 (2017).
Estradiol has been reported to enhance KC phagocytic capacity and depress
cytokine production including IL-6, TNF-α, macrophage inflammatory protein
(MIP)-1α and MIP-2

Hepatic System
Estrogen
Al-Tarrah, K., N. Moiemen, and J. M. Lord. "The influence of sex steroid hormones on the response to trauma and burn injury." Burns &
trauma 5.1 (2017).
Progesterone
Sex steroid hormones (SSH) may influence the outcome after injury
Gender differences in trauma outcomes such as
1. Reduction in liver congestion, portal
inflammation and focal necrosis
2. Enhanced Kupffer Cell function
3. Reduction IL-6, TNF-alfa and MIP
4. Increased expression of Bcl-2
5. Reduced ET-1 response
1. Reduced hepatic microvascular blood
flow
2. Diminished hepatocellular function

Intestine System
The intestinal tract is a site of intense immune cell activity that is poised to mount an
effective response against a pathogen
The intestinal immune system is the main immune . The main antibody produced in
the intestine is immunoglobulin (Ig) which is usually found in the form of dimers. IgA
relatively resistant to proteolysis so these antibodies are appropriate to be in the
intestinal environment which contains various digestive systems., IgA does not have an
inflammatory reaction, only bind to antigen and regulate it from the intestinal tract
Al-Tarrah, K., N. Moiemen, and J. M. Lord. "The influence of sex steroid hormones on the response to trauma and burn injury." Burns &
trauma 5.1 (2017).
The intestinal tract is a site of intense immune cell activity that is poised to mount an
effective response against a pathogen

Intestine System
Estrogen
Al-Tarrah, K., N. Moiemen, and J. M. Lord. "The influence of sex steroid hormones on the response to trauma and burn injury." Burns &
trauma 5.1 (2017).
Progesterone
Sex steroid hormones (SSH) may influence the outcome after injury
Gender differences in trauma outcomes such as
1. Reduction ET-1 response
2. Enhanced p38MAPK and Akt
Expression
3. Reduction MPO, ICAM-1, CINC-1,
CINC-3, MIR-2, Il-6
1. Enhances local pro-inflammatory respons

Does anyone have any questions?
Terima kasih

Reference
• Evrimler, Sehnaz, Irfan Okumuser, and Deniz Delibas. "Delayed small bowel perforation with
findings of severe ischemia following blunt abdominal trauma." Polish journal of radiology 82
(2017): 271.
• Vuerich, Marta, Simon C. Robson, and Maria Serena Longhi. "Ectonucleotidases in intestinal
and hepatic inflammation." Frontiers in immunology 10 (2019): 507.
• Al-Tarrah, K., N. Moiemen, and J. M. Lord. "The influence of sex steroid hormones on the
response to trauma and burn injury." Burns & trauma 5.1 (2017).
• Wagner, Nils, et al. "Ethyl pyruvate ameliorates hepatic injury following blunt chest trauma
and hemorrhagic shock by reducing local inflammation, NF-kappaB activation and HMGB1
release." PloS one 13.2 (2018): e0192171.

Reference
• Huber-Lang, Markus, John D. Lambris, and Peter A. Ward. "Innate
immune responses to trauma." Nature immunology 19.4 (2018): 327-
341.Vuerich, Marta, Simon C. Robson, and Maria Serena Longhi.
"Ectonucleotidases in intestinal and hepatic inflammation." Frontiers in
immunology 10 (2019): 507.
• O'Rourke MC, Landis R, Burns B. Blunt Abdominal Trauma. [Updated 2020
Jul 27]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls
Publishing; 2020 Jan-.