1)Shock/MODS/SIRS 2)Hematological principles in surgery

Shock
Shock is defined as tissue hypoperfusion that is insufficient to maintain normal aerobic metabolism

Determinants of Shock
Inadequate tissue perfusion
Sustained loss of effective circulatory blood volume Breakdown of cellular metabolism and microcirculatory homeostasis Hypoperfusion of peripheral tissue that leads to a diminutive transcapillary exchange function Disproportion between VO2 and DO2

Shock
Hemorrhagic/hypovolemic shock Cardiogenic shock Vasodilatory/septic shock Neurogenic shock Obstructive shock Traumatic shock

SIRS

Definition
SIRS
Sepsis Severe Sepsis Septic Shock Shock
2 or more of: Temp. >38C or <36C HR >90 bpm RR > 20 cpm or PaCO2 < 4.3 kPa WBCs >12 x 109/lit OR < 4 x 109/lit OR > 10% immature forms
SIRS due to infection Sepsis with evidence of organ hypoperfusion (eg. Oliguria, Lactic acidosis, confusion, etc..)
acidosis, confusion, etc..)

Severe sepsis with sys. BP < 90mmHg despite adequate fluid resuscitation or the requirement for resuscitation or the requirement for vasopressors/inotropes to maintain BP maintain BP

Pathophysiology of SIRS
The stimulation of multiple interacting systems such as:
Complement Cascade Cytokine cascades Arachidonic Acid Metabolites Cell Mediated Immunity Humoral Immune Mechanisms Clotting Cascade

IL-1
During an inflammatory response, it facilitates the movement of WBCs toward the injury, ischemia, or infected area It stimulates the release of arachidonic acid from phospholipids in the plasma membranes, leading to fever, hypotension, and decrease systemic vascular resistance. IL-1 also leads to muscle protein breakdown IL-1 works with other cellular immunity components to produce IL-2, which decreases blood pressure, systemic vascular resistance, and left ventricular ejection fraction. IL-2 may also increase left ventricular end diastolic volume, cardiac output, and heart rate

IL-6
Is a key messenger that can either trigger the rest of the cascade or its arrest Stimulates the release of acute phase reactors Its serum levels are consistent with the gravity of the immune reaction

Nitric Oxide
Nitric oxide is synthesised by inducible nitric oxide synthase (iNOS) in the vascular endothelium and smooth muscle in response to pro-inflammatory cytokines NO is the vasoactive mediator responsible for the fall in systemic vascular resistance underlying the hypotension in the late stages of SIRS and septic shock

Arachidonic Acid Cascade

Thromboxane A2
Is a potent vasoconstrictor and platelet aggregator Leads to tissue ischemia from hypoperfusion.

Leukotrienes leads to
Capillary endothelial permeability Bronchoconstriction Activation of neutrophils

The Complement Cascade

Controls the inflammatory process
Chemotaxis Opsonization Promotion of phagocytosis

Clotting Cascade
Fibrin is formed due to the injury of the vascular endothelium Chemical mediators stimulate the release of Hageman Factor and Thromboplastin These form clots at the site of the injury, attempting to stabilize the site Fibrinolysis is activated by the coagulation cascade, leading to mediator induced (DIC).

Bradykinin
The activation of the Hageman Factor stimulates the release of bradykinin Bradykinin creates vasodilatation and capillary leakage, therefore volume depletion.

Myocardial Depressant Factor

Myocardial depressant factor is a serum protein released by the hypoperfused and ischemic cells of the pancreas It decreases the velocity of contractions of myocardial cells, leading to decreased right and left ventricular ejection fractions

Beta Endorphins
Beta endorphins are released, by the pituitary and hypothalamus, in response to hypoperfusion They cause peripheral vasodilatation, and decrease cardiac contractility

Organ Manifestations
Cardiovascular
Skin warm and flushed Widened pulse pressure Cardiac output is but SVR is Eventually C.O. declines exacerbating hypoperfusion

Organ Manifestations
Pulmonary
Hypoxemia may be masked by hyperventilation Respiratory alkalosis Pulmonary edema Respiratory failure Bronchoconstriction ARDS

Organ Manifestations
CNS
Altered mental status Confusion Irritability Agitation Disorientation Lethargy Seizures Coma

Renal Oliguria: < 500 ml/day Metabolic Acidosis

Organ Manifestations
GIT
Impaired motility SGPT & SGOT Hyperbilirubinemia Hepatic necrosis Hypoprothrombinemia Hypoglycemia
Blood or WBCs PT and PTT or Platelets Anemia

Investigations
Cytokines assay (IL-6, IL-8 & TNF) Blood Culture Burn eschar biopsy with culture & sensitivity Serum Procalcitonin
The only lab test that differentiates
SIRS (0.5 -2 ng/dl) from Sepsis (>2 & <10 ng/dl) from MOD (>10 and often >100ng/dl)

Treatment
Elimination of triggering factor LPS
Antibiotics according to C&S Gut decontamination

LPC through
Prompt early surgical eschar excision Chemical elimination eg. Cerium Nitrate

Treatment
Supportive Medical Surgical

Supportive Therapy
Volume replacement +ve inotropes & vasopressors Ventilation (Pressure support or PEEP) Nutritional Support
Iso-Osmotic Feedings TPN PPN Immune Modulatory Foods such as Arginine, Glutamine & fish oils

Medical
Potent anti-oxidants
Methylene Blue given IV Acetyl Cysteine Vitamin C

Immune Modulators
Ibuprofen (proved of limited value) Centoxin: an Ab to endotoxins NOSI (nitric oxide synthetase inhibtor) very much accepted IL-6 blockers Experimental

Surgical Excision
Best option = Early excision + coverage Best performed within the 1st 72 hours and after resuscitation Is the only way to break the circle

Prognosis
Death in 60% of cases of late stages & shock in patients with no previous history of medical conditions Death rate is higher if MOD develops & is dependant on no. of organs affected
3 organs 85% 4 organs 95% 5 organs 99%

MODS

Definition
Multiple Organ Dysfunction Syndrome (MODS) is dysfunction of two or more organs (initially uninvolved developing within a short period of time.

Anti-inflammatory reaction IL-10, IL-4, TGF- IL-1ra ,Lipoxin Cell elimination

Pro-inflammatory reaction TNF-a, IL-1, IL-6, IFN TXA2, PAF Cell activation

MODS is the failure of the balance

Uncontrolled inflammatory response

Infection/Injury

Uncontrolled inflammatory response SIRS CARS

Controlled inflammatory response

Infection/injury controlled

MODS

HEMATOLOGICAL PRINCIPLES IN SURGERY

Haemostasis overview:
BV Injury Neural

Contact/ Tissue Factor

Platelet Aggregation Primary hemostatic plug Platelet Activation Coagulation Cascade

Blood Vessel Constriction

Reduced
Blood flow

Fibrin formation

Stable Hemostatic Plug

Haemostasis:

Platelet activation Haemostatic plug Vasoconstriction N Coagulation Stable clot formation Clot dissolution

Coagulation:
Contact activationIntrinsic system Tissue factor activation Extrinsic Common pathamplification Fibrin formation Fibrin lysis.

Bleeding: Clinical Features

1. Local - Vs - General, spontaneous . . 2. Hematoma & Joint bleed - Coagulation 3. Skin/Mucosal Petechiae & Purpura PLT 4. wound / surgical bleeding Immediate - (PLT) Delayed - (Coagulation)

Disorders of Hemostasis
Vascular disorders
Scurvy, easy bruising,

Platelet disorders
Low Number or abnormal function

Coagulation disorders
Factor deficiency.

Mixed/Consumption: DIC

Haemophilia
Congenital deficiency -Factor 8 (A) or 9 (B) Bleeding Haematoma, joint etc. Gene on X chromosome.
(Carrier females, Males suffer)

Prolonged PTT but normal PT. FFP or Factor replacement Life long

Ideopathic T. Purpura - ITP

Young female 20-35y (15-50) Easy bruising, Petechiae, menorrhagia Anti PLT Antibody (IgG) destruction of plt Low Platelet number.

Disorders of platelets
Decreased Number: Thrombocytopenia
Decreased Production Decreased Survival Immune (ITP) Increased utilization - DIC

Defective Platelet function:

Acquired Drugs Aspirin, MPS, MDS Congenital Eg. Thrombasthenia.

 Bleeding time BV, PLT

Routine Investigations:

Clotting time inaccurate 10-20min Prothrombin time Extrinsic (2,5,10 + 7),

aPTT Intrinsic (2,5,10 + 8,9,12)
Haemophilia, Congenital.
DIC & Heparin therapy. Acquired diseases, liver dis, warfarin therapy

ivy template method - 3-8min

Trombin Time: Fibrinogen (common path) CBC Plt Count FDP Fibrinogen Degradation Products DIC

Special Investigations:
Specific Factor Assays Platelet function studies
Aggregometry, Adhesion studies Immuno-fluorescence

Electrophoresis Bone marrow examination plt Molecular Biology FISH

Hemostatic Agents for Use in Surgery

Mechanical Tools Matrix Absorbable Hemostatic Products Thrombin, Goops, Pastes, and Putties Systemic Biologics

Mechanical Tools
Finger Gauze Sponge Cautery Laser Radio-frequency energy Argon Beam Coagulator Clips and suture CUSA Harmonic Scalpel

Absorbable Hemostatic Agents

Oxidized CelluloseSurgicelLow pHBactericidal Gelatin SpongeGelfoam/Surgifoam Neutral pHGood carrier MicrofibrillarCollagenAvitene Biodegradable MatrixAbsorb BloodActivate PlateletsInduce Coagulation

Biologic Hemostatic Agents

Bovine ThrombinSemi pure cow thrombinActivates platelets and fibrin Immunologic effects FloSealBovine (now human) thrombinGelatin Sponge mix Easy to use CoSeal Polyethylene Glycol glue No obvious biologic effect/immunology

Biologic Hemostatic Agents

Fibrin Sealants Tisseal and Crosseal Human thrombin fibrinogen mixEach contains an antifibrinolytic(bovine aprotinin and TMA)Hard to mixBetter sealant than hemostat
BioGlue Bovine albumin and gluteraldehyde Tans tissues - cant use around nerve tissue Easy to use Good for aortic dissection question emboli