ENDOTHELIUM-MEDIATED

INJURY
TUGAS PRESENTASI PRABEDAH
OLEH:
1. AMALIA F ASHARI,
2. LUH PUTU NEOLITA PRADNYA W,
3. MENIK SAYEKTI,
VASCULAR ENDOTHELIUM

 Vascular endothelium has overall anticoagulant, mediated via production and

cell surface expression heparin sulfate, dermatan sulfate, tissue fact.
pathway inhibitor, protein S, thrombomodulin, plasminogen
 Endothelial cells also perform as barrier that regulate tissue migration of
circulating cells.

NEUTROPHIL-ENDOTHELIUM INTERACTION
• The inflammatory response to infection facilitates
neutrophil and other immunocyte increased
vascular permeability, chemoattractants & endothelial
adhesion factor as selectin
CHEMOKINES

 Chemokines are a family of small proteins that were first

identified through their chemotactic and activating
effect on inflammatory cells.
 There are more than 50 different chemokines and 20
chemokine receptors that have been identified
 They are soluble protein, bind to glycosaminoglycans on
the cell surface can form a fixed chemical gradient
that promotes immune cell exit to target areas
• CAPTURE : initial recognition between
leukocyte and endothelium, which
circulating leukocyte at endothelial
surface
• FAST ROLLING (20-50μm/s): rapid L-
selection shedding from cell surface to
endothelial bond
• SLOW ROLLING (10-20 μm/s):
predominantly mediated by P-selection,
lowest rolling (3-10 μm/s) before arrest
mediated by E-selectin.
• ARREST(Firm adhesion): transmigration
mediated by β-integrins and
immunoglobulin
NITRIC OXIDE

 Nitric Oxide (NO) known as endothelium-derived relaxing factor on

vascular smooth muscle.
 Relaxation vascular smooth muscle releasing output NO
 Nitric oxide reduce microthrombosis by reducing platelets
adhesion and aggregation and interfering leukocytes adhesion to
the endothelium
 NO synthesis increased in response to proinflamatory Upregulation
mediators (TNFα and Ilβ), as well as microbial product NOS
expression
 Endogenous NO formation derived largely from action of NO
synthase (NOS) (NOS3) by expressed in endothelial cell
 Vasodilatory effect of NO are mediated by Guanyl cyclase
(enzyme in vascular smooth muscle cell)

NO + guanyl Smooth muscle

cyclase cGMP signaling relaxation

GTP
 Increased NO is also detectable in septic shock associated with low
peripheral vascular resistence and hypotension.
 Increased NO in sepsis NOS activity and expression, cytokines
release inhibition of NO production seemed initially to be
severe sepsis
Prostacyclin

 Prostacyclin (PGI) produced by vascular endothelial cells

inhibit platelets aggregation and promotes vasodilation
 Prostacyclin (PGI) in pulmonary system reduced pulmonary
blood pressure and bronchial hyperresponsiveness
 Prostacyclin (PGI) in kidneys modulated renal blood flow and
GFR rate
 In systemic inflammation, PGI endothelium expression is impaired
 Exogenous prostacyclin (PGI) analogues IV or inhaled
increased oxygenation in acute lung injury, improved cardiac index,
and oxygen delivery in septic
Endothelial interaction with smooth muscle cells
and intraluminal platelets

Prostacyclin (prostaglandin/PGI) is
derivered from arachidonic acid (AA),
nitric oxide (NO) is derived from L-
arginine. The increase cyclic
adenosine monophosphate(cAMP)
and cyclic guanosine
monophosphate(cGMP) results
smooth muscle relaxation and inhibit
platelets thrombus formation
ENDOTHELINS
 Endothelins are potent mediators of vasoconstriction.
 Endothelins composed of three members : ET-1, ET-2, ET-3. ET-1 synthesized
primarily by endothelial cells, is the most potent endogenous vasoconstrictor
 Endothelins release is upregulated in response to hypotension, injury, anoxia

PLATELET - ACTIVATING FACTOR (PAF)

• During acute inflammation PAF is released by immune

cells
• Human sepsis is associated with a reduction in the levels of
PAF which in activated PAF by removing an acetyl group
NATRIURETIC PEPTIDES

 The natriuretic pptides, atrial natriuretic factor (ANF) & brain natriuretic peptides
(BNP) are family of peptides that are released primarily by atrial tissue
 ANF and BNP increased in the setting of cardiac disorders, recent evidence
indicates some distinctions in the setting of inflammation
 Elevated pro BNP has been detected in septic patient
THANK YOU