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A.A.A.N.

SUSRAINI
DEPARTMENT OF PATHOLOGY
MEDICAL FACULTY UDAYANA
UNIVERSITY/SANGLAH HOSPITAL
HEMODYNAMIC DISORDERS,
THROMBOEMBOLIC DISEASE, AND
SHOCK
CONTAIN :

EDEMA EMBOLISM
HYPERHEMIA AND CONGESTION PULMONARY
THROMBOEMBOLISM
HEMORRHAGE
SYSTEMIC
HEMOSTASIS AND THROMBOSIS
THROMBOEMBOLISM
NORMAL HEMOSTASIS
FAT EMBOLISM
ENDOTHELIUM
AIR EMBOLISM
PLATELETS
AMNIOTIC FLUID EMBOLISM
COAGULATION CASCADE
INFARCTION
THROMBOSIS
SHOCK
DISSEMINATED INTRAVASCULAR
PATHOGENESIS OF SEPTIC
COAGULATION (DIC)
SHOCK
EDEMA
Peningkatan abnormal cairan interstisial dalam jaringan
Kumpulan cairan pada cavitas yang berbeda menunjukkan
bervariasi :
- hydrothorax
- hydropericardium
- hydroperitoneum (ascites).
- anasarca is a severe and generalized edema with
widespread subcutaneous tissue swelling.

Penumpukan cairan di dalam jaringan interstisial atau di


dalam vakum.Jaringan interstisial (
NORMALLY
• Kurang lebih 60% berat tubuh adalah air.
• 2/3 cairan tubuh adalah intraseldan sisanya adalah di
compartemen ekstraseluler.
• mostly the interstitium (or third space) that lies between cells.
only about 5% of total body water is in blood plasma
MECHANISM EDEMA DUE TO INCREASED
HYDROSTATIC PRESURE
LOCAL INCREASED HP
DEEP VENOUS
THROMBOSIS
GENERALIZED VENOUS
PRESURE INCREASE
- CHF
EDEMA CAUSED BY INCREASED HYDROSTATIC
PRESSURE OR REDUCED PLASMA PROTEIN IS
TYPICALLY A PROTEIN-POOR FLUID:
TRANSUDATE.

EDEMA FLUID OF THIS TYPE IS SEEN IN PATIENTS


SUFFERING FROM HEART FAILURE, RENAL FAILURE,
HEPATIC FAILURE, AND CERTAIN FORMS OF
MALNUTRITION
INFLAMMATORY EDEMA IS A PROTEIN-RICH :
EXUDATE THAT IS A RESULT OF INCREASED
VASCULAR PERMEABILITY
INFLAMATORY EDEMA
2. HYPERHEMIA AND CONGESTION
 HYPERHEMIA IS ACTIVE PROCESS RESULTING ARTERIOLAR
DILATION IN AT SITES OF INFLAMMATION OR EXERCISE
 CONGESTION IS PASSIVE PROCESS RESULTING FROM
IMPAIRED OUT FLOW FROM A TISSUE
 CHRONIC PASSIVE CONGESTION LONG-STANDING
CONGESTION COUSE SMALL FOCI HEMMORHAGE
HEMOSIDERIN LADEN MACROPHAGE/ HEART FAILURE CELL
MICROSCOPIC CONGESTON OF THE LUNG AND LIVER

A C

A. PASSIVE CONGESTION OF LUNG.


HEMOSIDERIN LADEN MACROFAG IN
LUNG OF PATIENT WITH
CONGESTIVE HEART FAILURE
B. PULMONARY EDEMA. A PATIENT OF
CONGESTIVE HEART FAILURE
C. PASSIVE CONGESTION OF LIVER.
REFLECTING CONGESTIVE HEART
FAILURE OF THE RIGHT VENTRICLE
B
3. HEMORRHAGE
 HEMORRHAGE GENERALLY INDICATES EXTRAVASATION OF BLOOD DUE TO
VESSEL RUPTURE
 HEMATOMA
 PETECHIAE- THROMBOCYTOPEMIA . 1- 2mm
 PURPURA-VASCULITIES OR INCREASED VASCULAR FRAGILITY.
SLIGHTLY LARGER (≥3 mm) HEMORRHAGES
 ECCHYMOSES. LARGER (>1 -2 cm) SUBCUTANEOUS
HEMATOMA
 LARGE ACCUMULATION OF BLOOD (HEMOTHORAX,
HEMOPERICARDIUM, HEMOPERITONIUM, OR HEMARTHROSIS)
 HEMORRHAGE EXTERNAL PRODUCE HEMATEMESIS, HEMOPTOE,
MENORRHAGE AND METRORRHAGE, EPISTAXIS AND BLEEDING PER
ANUM
 HEMORRHAGE HYPOVOLEMIC SHOCK
• MINUTE HEMORRHAGES INTO SKIN, MUCOUS
MEMBRANES, OR SEROSAL SURFACES ARE CALLED
PETECHIAE
• THESE ARE MOST COMMONLY ASSOCIATED WITH
LOCALLY INCREASED INTRAVASCULAR PRESSURE,
LOW PLATELET COUNTS (THROMBOCYTOPENIA )
DENGUE FEVER
BLEEDING DISORDERS : HEMORRHAGE
DIATHESESS
 BLEEDING DISORDERS CAUSED BY VESSEL WALL
ABNORMALITIES
 BLEEDING RELATED TO REDUCED PLATELET NUMBER:
THROMBOCYTOPENIA
 BLEEDING DISORDER RELATED TO DEFECTIVE PLATELET
FUNCTIONS
 HEMORRHAGE DIATHESES RELATED TO ABNORMALITIES IN
CLOTTING FACTORS
 DISSAMINATED INTRAVASCULAR COAGULATION (DIC) – IS NOT
PRIMARY DISEASES BUT COMPLICATION ACTIVATED TROMBIN
4. HEMOSTASIS AND THROMBOSIS
 NORMAL HEMOSTASIS AT SITE VASCULAR INJURY
 REFLEX NEUROGENIC MECHANISM - ENDOTELIN
 PLATELET ADHESION AND ACTIVATION ECM
TEMPORARY HEMOSTATIC PLUG
 ACTIVATION OF COAGULATION CASCADE IS DERIVEN BY TISSUE
FACTOR THROMBIN
FIBRIN
 ACTIVATION OF COUNTER - REGULATORY MECHANISM
4.1. ROLE OF ENDOTHELIUM AS A NORMAL HEMOSTASIS

• ANTITHROMBOTIC PROPERTIES

– ANTIPLATELET EFFECT
– ANTICOAGULANT EFFECT
– FIBRINOLYTIC EFFECT
• PROTHROMBOTIC PROPERTIES

– PLATELET EFFECTS
– PROCOAGULATION EFFECTS
– ANTIFIBRINOLITIC EFFECTS
4.2. ROLE OF PLATELETS AS HEMOSTASIS

• PLATELET ADHESION
• SECRETION (RELEASE REACTION)
• PLATELET AGGREGATION
ENDOTHELIUM PROCOAGOLATIVE
ACTIVITY
SERIES OF PLATELET EVENT CAN BE SUMMARIZED AS FOLLOWS :

• PLATELET ADHERE TO ECM AT SITES OF ENDOTHELIAL INJURY


AND BECOME ACTIVATED
• ON ACTIVATION, THEY SECRETE GRANULE PRODUCTS (e.g.,
ADP) AND SYNTHESIZE TxA2
• PLATELET ALSO EXPOSE PHOSPHOLIPID COMPLEXES THAT
ARE IMPORTANT IN THE INTRINSIC COAGULATION PATHWAYS
• INJURED OR ACTIVED ENDOTHELIAL CELL EXPOSE TISSUE
FACTOR, WHICH TRIGGER THE EXTRINSIC COAGULATION
CASCADE
• RELEASED ADP STIMULATES THE FORMATION OF A PRIMARY
HEMOSTATIC PLUG, WHICH IS EVENTUALLY CONVERTED (VIA
ADP, THROMBIN, AND TxA2) INTO A LARGE, DEFINITIVE,
SECONDARY PLUG
• FIBRIN DEPOSITION STABILIZED ANCHORS THE
AGGREGATED PLATELET
PLATELET ADHESION
4.3. ROLE OF COAGULATION CASCADE
THE BLOOD
COAGULATION
SCHEME HAS BEEN
DIVIDED INTO
EXTRINSIC
PATHWAYS,
CONVERGING WHERE
FACTOR X IS
ACTIVATED
CONVERSION OF FACTOR X TO Xa AND THEN II
(PROTHROMBIN) TO IIa (THROMBIN)
THE CENTRAL ROLES OF THROMBIN IN HEMOSTASIS AND CELLULAR
ACTIVATION

IN ADDITION TO A CRITICAL FUNCTION IN


GENERATING CROSS-LINKED FIBRIN (VIACLEAVAGE
OF FIBRINOGEN TO FIBRIN AND ACTIVATION OF
FACTOR XIII), THROMBIN ALSO DIRECTLY INDUCES
PLATELET AGGREGATION AND SECRETION (e.g., OF
TXA2). THROMBIN ALSO ACTIVATES ENDOTHELIUM
TO GENERATE LEUKOCYTE ADHESION MOLECULES
AND A VARIETY OF FIBRINOLYTIC (t-PA),
VASOACTIVE (NO, PGI2), OR CYTOKINE (PDGF)
MEDIATORS, LIKEWISE , MONONUCLEAR
INFLAMMATORY CELLS MAY BE ACTIVATED BY THE
DIRECT ACTIONS OF THROMBIN. ECM ,
EXTRACELLULAR MATRIX; NO NITRIC OXIDE; PDGF,
PLATELET DERIVED GROWTH FACTOR; PGL2 ,
PROSTACYCLIN; TXA2, THROMBOXANE A2; t-PA ,
TISSUE TYPE PLASMINOGEN ACTIVATOR . SEE –FIG
4-7 FOR ADDITIONAL ANTICOAGULANT
MODULATORS OF THROMBIN ACTIVITY, SUCH AS
ANTITHROMBIN III AND THROMBOMODULIN.
(MODIFIED WITH PERMISSION FROM SHOUN
COUGHLIN, MD, PhD, CARDIOVASCULART
RESEARCH OF CALIFORNIA AT SANFRANCISCO).
CONTROL MECHANISM OF THROMBOSIS

POSPOLIPID ARE CLEARED BY LIVER AND


MACROPHAGE
ANTITHROMBIN III
ENDOTHELIAL THROBOMODULIN
ENDOTHELIAL t-PA GENERATES PLASMIN FROM
CIRCULATING PLASMINOGEN
ENDOTHELIUM MODULATE COAGULATION BY
RELEASING PLASMINOGEN ACTIVATOR INHIBITOR
THROMBOSIS

THREE PRIMER OF NORMALITY THAT LEAD TO THROMBUS FORMATION (CALLED VIRCHOW’S


TRIAD ) : 1. ENDOTHELIAL INJURY
2. INJURY STATIS OR TURBULEND BLOOD FLOW
3. HYPERCOAGULABILITY OF THE BLOOD
CONTROL MECHANISM OF THROMBOSIS

POSPOLIPID ARE CLEARED BY LIVER AND


MACROPHAGE
ANTITHROMBIN III
ENDOTHELIAL THROBOMODULIN
ENDOTHELIAL t-PA GENERATES PLASMIN FROM
CIRCULATING PLASMINOGEN
ENDOTHELIUM MODULATE COAGULATION BY
RELEASING PLASMINOGEN ACTIVATOR INHIBITOR
VIRCHOW TRIAD
IN THROMBOSIS
TYPE OF THROMBOSIS
VENOUS THROMBOSIS (PHLEBOTHROMBOSIS)
ARTERIAL AND CARDIAC THROMBOSIS
TROMBI ON THE HEART VALVES ARE CALL
PEGETATION IN INFECTINE ENDOCARDITIS, STRERIL
VERROCOUS ENDOCARDITIS (LIBMAN SACK
VEROCARDITIS)
POSTMORTEM CLOTS
VENOUS THROMBOSIS
• PATOGENESIS
– STASIS ( HEART FAILURE, CHRONIC VENOUS
INSUFIENCY, PROLONG BED REST )
– INJURY
– HYPER COAGULATION
– ADVANCED AGE
– SICKLE CELL DISEASES
• PATHOLOGY: LYSIS, ORGANIZATION, PROPOGATION,
EMBOLIZATION
Arterial and Cardiac Thrombosis

• ATHEROSCLEROSIS IS A MAJOR CAUSE OF ARTERIAL


THROMBOSES, BECAUSE IT IS ASSOCIATED WITH LOSS OF
ENDOTHELIAL INTEGRITY AND WITH ABNORMAL
VASCULAR FLOW .
• MYOCARDIAL INFARCTION CAN PREDISPOSE TO CARDIAC
MURAL THROMBI BY CAUSING DYSKINETIC MYOCARDIAL
CONTRACTION AS WELL AS DAMAGE TO THE ADJACENT
ENDOCARDIUM AND RHEUMATIC HEART DISEASE MAY
ENGENDER ATRIAL MURAL THROMBI
BESIDES LOCAL OBSTRUCTIVE CONSEQUENCES, CARDIAC AND
AORTIC MURAL THROMBI CAN ALSO EMBOLIZE PERIPHERALLY : THE
BRAIN, KIDNEYS, AND SPLEEN ARE PARTICULARLY LIKELY TARGETS
BECAUSE OF THEIR RICH BLOOD SUPPLY
DISSEMINATED INTRAVASCULAR COAGULATION (DIC)

DISORDERS RANGING FROM OBSTETRIC


COMPLICATIONS TO ADVANCED MALIGNANCY CAN BE
COMPLICATED BY DIC, THE SUDDEN OR INSIDIOUS
ONSET OF WIDESPREAD FIBRIN THROMBI IN THE
MICROCIRCULATION.
CIRCULATORY INSUFFICIENCY, PARTICULARLY IN THE
BRAIN, LUNGS, HEART, AND KIDNEYS.
TO COMPLICATE MATTERS, THE WIDESPREAD
MICROVASCULAR THROMBOSIS RESULTS IN
PLATELET AND COAGULATION PROTEIN
CONSUMPTION (HENCE THE SYNONYM
CONSUMPTION COAGULOPATHY), AND AT THE
SAME TIME, FIBRINOLYTIC MECHANISMS ARE
ACTIVATED.
AN INITIALLY THROMBOTIC DISORDER CAN EVOLVE
INTO A BLEEDING CATASTROPHE. IT SHOULD BE
EMPHASIZED THAT DIC IS NOT A PRIMARY DISEASE
BUT RATHER A POTENTIAL COMPLICATION OF ANY
CONDITION ASSOCIATED WITH WIDESPREAD
ACTIVATION OF THROMBIN
5. EMBOLISM

TYPE OF EMBOLISM
 PULMONARY EMBOLI
 SYSTEMIC THROMBOEMBOLI ORGAN THAT SUFFER
: BRAIN, INTESTINAL, LOWER EXTRAMATY, KIDNEY,
HEART (CORONERY ARTERI EMBOLISM AND
RESULTING MIOCARDIAL INFARC)
 FAT AND MARROW EMBOLISM
 AIR EMBOLISM
 AMNIOTIC FLUID EMBOLISM
SYSTEMIC THROMBOEMBOLISM
• MOST (80%) ARISE FROM INTRACARDIAC MURAL
THROMBOSIS.
• THE REMAINDER ORIGINATE FROM AORTIC ANEURYSMS,
THROMBI ON ULCERATED ATHEROSCLEROTIC PLAQUES OR
FRAGMENTATION OF A VALVULAR VEGETATION , WITH A
SMALL FRACTION DUE TO PARADOXICAL EMBOLI.
10% TO 15% OF SYSTEMIC EMBOLI ARE OF
UNKNOWN ORIGIN.
MAJOR SITES FOR ARTERIOLAR EMBOLIZATION ARE
THE LOWER EXTREMITIES (75%).
THE BRAIN (10%), WITH THE INTESTINES, KIDNEYS,
SPLEEN, AND UPPER EXTREMITIES INVOLVED TO A
LESSER EXTENT.

THE CONSEQUENCES OF EMBOLIZATION IN A


TISSUE DEPEND ON ITS VULNERABILITY TO
ISCHEMIA, THE CALIBER OF THE OCCLUDED
VESSEL, AND WHETHER THERE IS A COLLATERAL
BLOOD SUPPLY.
IN GENERAL, ARTERIAL EMBOLI CAUSE INFARCTION
OF THE AFFECTED TISSUES
VENOUS EMBOLI: WHICH TEND TO LODGE
PRIMARILY IN ONE VASCULAR BED (THE
LUNG), ARTERIAL EMBOLI CAN TRAVEL TO A
WIDE VARIETY OF SITES; THE POINT OF
ARREST DEPENDS ON THE SOURCE AND
THE RELATIVE AMOUNT OF BLOOD FLOW
THAT DOWNSTREAM TISSUES RECEIVE.
SYSTEMIC THROMBOEMBOLISM
FAT AND MARROW EMBOLISM

FAT EMBOLISM SYNDROME IS THE TERM


APPLIED TO THE MINORITY OF PATIENTS WHO
BECOME SYMPTOMATIC. IT IS
CHARACTERIZED BY PULMONARY
INSUFFICIENCY, NEUROLOGIC SYMPTOMS,
ANEMIA, AND THROMBOCYTOPENIA, AND IS
FATAL IN ABOUT 5% TO 15% OF CASES
AMNIOTIC FLUID EMBOLISM

AMNIOTIC FLUID EMBOLISM IS AN OMINOUS


COMPLICATION OF LABOR AND THE IMMEDIATE
POSTPARTUM PERIOD. ALTHOUGH THE INCIDENCE IS ONLY
APPROXIMATELY 1 IN 40,000 DELIVERIES, THE MORTALITY
RATE IS UP TO 80%
6. INFARCTION
 INFARC IS AN AREA OF ISHEMIC NECROSIS CAUSED BY
OCCLUSION OF EITHER THE ARTERIAL SUPPLY OR THE
VENOUS DRAINAGE
 MORFOLOGY
 RED INFARC OCCUR INFARC WITH VENOUS OCCLUSION, IN
LOOS TISSUE AS A LUNG, IN TISSUE WITH DUEL CIRCULATION,
TISSUE IN CONGESTION, AND REPERFUTION
 WHITE INFARC OCCUR WITH ARTERIAL OCCLUTION IN SOLID
ORGAN WITH AND ARTERIAL CIRCULATIN e.g. HEART, KIDNEY,
SPLEEN
• ACUTE INFLAMMATION IS PRESENT ALONG THE MARGINS
OF INFARCTS WITHIN A FEW HOURS AND IS USUALLY WELL
DEFINED WITHIN 1 TO 2 DAYS. EVENTUALLY THE
INFLAMMATORY RESPONSE IS FOLLOWED BY A REPARATIVE
RESPONSE BEGINNING IN THE PRESERVED MARGINS
• MOST INFARCTS ARE ULTIMATELY REPLACED BY SCAR. THE
BRAIN IS AN EXCEPTION TO THESE GENERALIZATIONS, AS
CENTRAL NERVOUS SYSTEM INFARCTION RESULTS IN
LIQUEFACTIVE NECROSIS.
SHOCK
 FINAL COMMON PATHWAY FOR SEVERAL POTENTIALLY
LETHAL CLINICAL EVENTS, INCLUDING SEVERE HEMORRHAGE,
EXTENSIVE TRAUMA OR BURNS, LARGE MYOCARDIAL
INFARCTION, MASSIVE PULMONARY EMBOLISM, AND
MICROBIAL SEPSIS.

 CHARACTERIZED BY SYSTEMIC HYPOTENSION DUE EITHER TO


REDUCED CARDIAC OUTPUT OR TO REDUCED EFFECTIVE
CIRCULATING BLOOD VOLUME  IMPAIRED TISSUE
PERFUSION AND CELLULAR HYPOXIA.
CAUSES OF SHOCK
 Cardiogenic shock:
 intrinsic :
 myocardial damage (infarction)
 ventricular arrhythmias,
 extrinsic :
 compression :cardiac tamponade
 outflow obstruction pulmonary embolism
 Hypovolemic shock :
 massive hemorrhage
 fluid loss from severe burns.
 Diarrhea
 dehidration
 Septic shock :
 vasodilation & peripheral pooling of blood as part of a
systemic immune reaction to bacterial or fungal
infection.
• NEUROGENIC SHOCK :
– LOSS OF VASCULAR TONE AND PERIPHERAL
POOLING OF BLOOD, OCCUR IN THE SETTING OF
ANESTHETIC ACCIDENT OR A SPINAL CORD INJURY.
• ANAPHYLACTIC SHOCK :
– SYSTEMIC VASODILATION AND INCREASED
VASCULAR PERMEABILITY CAUSED BY AN IGE–
MEDIATED HYPERSENSITIVITY REACTION.IN THESE
SITUATIONS, ACUTE WIDESPREAD VASODILATION
RESULTS IN TISSUE HYPOPERFUSION AND
HYPOXia.
CLASSIFICATION OF SHOCK
THE MAJOR FACTORS CONTRIBUTING SHOCK
PATHOPHYSIOLOGY

• INFLAMMATORY MEDIATORS
• ENDOTHELIAL CELL ACTIVATION AND INJURY
• METABOLIC ABNORMALITIES
• IMMUNE SUPPRESSION
• ORGAN DYSFUNCTION
INFLAMMATORY MEDIATORS

VARIOUS MICROBIAL CELL WALL CONSTITUENTS


ENGAGE RECEPTORS :
- NEUTROPHILS
- MONONUCLEAR INFLAMMATORY CELLS
- ENDOTHELIAL CELLS  LEADING TO CELLULAR
ACTIVATION
-UPON ACTIVATION, INFLAMMATORY CELLS PRODUCE TNF, IL-1,
IFN-Γ, IL-12, AND IL-18
- OTHER INFLAMMATORY MEDIATORS: HIGH MOBILITY GROUP
BOX 1 PROTEIN (HMGB1).
- REACTIVE OXYGEN SPECIES AND LIPID MEDIATORS SUCH AS
PROSTAGLANDINS AND PLATELET ACTIVATING FACTOR (PAF)
ARE ALSO ELABORATED.
THE COMPLEMENT CASCADE IS ALSO ACTIVATED BY MICROBIAL
COMPONENTS, BOTH DIRECTLY AND THROUGH THE
PROTEOLYTIC ACTIVITY OF PLASMIN, RESULTING IN THE
PRODUCTION OF ANAPHYLOTOXINS (C3A, C5A)
CHEMOTACTIC FRAGMENTS (C5A)
OPSONINS (C3B) THAT CONTRIBUTE TO THE PRO-
INFLAMMATORY STATE
ENDOTHELIAL CELL ACTIVATION AND INJURY

ENDOTHELIAL CELL ACTIVATION BY MICROBIAL CONSTITUENTS


OR INFLAMMATORY MEDIATORS PRODUCED BY LEUKOCYTES
HAS THREE MAJOR SEQUELAE:
1. THROMBOSIS
2. INCREASED VASCULAR PERMEABILITY
3. VASODILATION
THE PRODUCTION OF OTHER ENDOTHELIAL ANTI-COAGULANT
FACTORS:
- TISSUE FACTOR PATHWAY INHIBITOR
- THROMBOMODULIN
- PROTEIN C
MICROBIAL COMPONENTS SUCH AS ENDOTOXIN CAN
ACTIVATE COAGULATION DIRECTLY THROUGH FACTOR XII
AND INDIRECTLY THROUGH ALTERED ENDOTHELIAL
FUNCTION
METABOLIC ABNORMALITIES

SEPTIC PATIENTS EXHIBIT INSULIN RESISTANCE AND


HYPERGLYCEMIA

TNF AND IL-1, STRESS-INDUCED HORMONES: GLUCAGON,


GROWTH HORMONE, GLUCOCORTICOIDS, CATECHOLAMINES
THE PRO-INFLAMMATORY CYTOKINES :
SUPPRESS INSULIN RELEASE WHILE
SIMULTANEOUSLY PROMOTING INSULIN
RESISTANCE IN THE LIVER AND OTHER TISSUES
HYPERGLYCEMIA DECREASES NEUTROPHIL
FUNCTION.
THE ENDOTHELIUM ALSO INCREASES ITS EXPRESSION OF
INDUCIBLE NITRIC OXIDE SYNTHETASE AND THE
PRODUCTION OF NITRIC OXIDE (NO).

THESE ALTERATIONS, A LONG WITH INCREASES IN


VASOACTIVE INFLAMMATORY MEDIATORS (C3A, C5A, AND
PAF) CAUSE THE SYSTEMIC RELAXATION OF VASCULAR
SMOOTH MUSCLE, LEADING TO HYPOTENSION AND
DIMINISHED TISSUE PERFUSION.
IMMUNE SUPPRESSION
THE HYPERINFLAMMATORY STATE INITIATED BY SEPSIS CAN
ACTIVATE COUNTER-REGULATORY IMMUNOSUPPRESSIVE
MECHANISMS WHICH MAY INVOLVE BOTH INNATE AND
ADAPTIVE IMMUNITY
PROPOSED MECHANISMS FOR THE IMMUNE SUPPRESSION
INCLUDE A SHIFT FROM PRO-INFLAMMATORY (TH1) TO ANTI-
INFLAMMATORY (TH2) CYTOKINES
PRODUCTION OF ANTI-INFLAMMATORY MEDIATORS
• SOLUBLE TNF RECEPTOR
• IL-1 RECEPTOR ANTAGONIST
• IL-10
• LYMPHOCYTE APOPTOSIS
ORGAN DYSFUNCTION

SYSTEMIC HYPOTENSION, INTERSTITIAL EDEMA, AND SMALL


VESSEL THROMBOSIS ALL DECREASE THE DELIVERY OF
OXYGEN AND NUTRIENTS TO THE TISSUES, WHICH FAIL TO
PROPERLY UTILIZE THOSE NUTRIENTS THAT ARE DELIVERED
DUE TO CHANGES IN CELLULAR METABOLISM.
- HIGHLEVELS OF CYTOKINES AND SECONDARY MEDIATORS
MAY DIMINISH MYOCARDIAL CONTRACTILITY AND CARDIAC
OUTPUT, AND INCREASED VASCULAR PERMEABILITY AND
ENDOTHELIAL INJURY CAN LEAD TO THE ADULT
RESPIRATORY DISTRESS SYNDROME (ARDS)

- THESE FACTORS MAY CONSPIRE TO CAUSE THE FAILURE OF


MULTIPLE ORGANS, PARTICULARLY THE KIDNEYS, LIVER,
LUNGS, AND HEART, CULMINATING IN DEATH.
STAGE OF SHOCK

 NO PROGRESSIVE PHASE- NORMAL PERPUTION


 PROGRESSIVE STAGE – HYPOPERPUTION
 IRREVERSSIBLE STAGE – HYPODYNAMIC DEFFECT
 HYPOXIA INJURY IN BRAIN, HEART, LUNG, KIDNEY,
ADRENAL GLAN AND GASTROINTESTINAL
MULTIPLE ORGA FAILURE
 CLINICAL HYPOTENTION RAPID PULSE TACHYCARDY
AND COOL AND CYANOTIC
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