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Thrombosis Shock 2008. Normal hemostasis Thrombosis – factors, morphology Embolism Shock DIC TTP,HUS Doc. MUDr. L. Boudová, Ph. D.

Dec 25, 2015

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Page 1: Thrombosis Shock 2008. Normal hemostasis Thrombosis – factors, morphology Embolism Shock DIC TTP,HUS Doc. MUDr. L. Boudová, Ph. D.

ThrombosisShock 2008

Page 2: Thrombosis Shock 2008. Normal hemostasis Thrombosis – factors, morphology Embolism Shock DIC TTP,HUS Doc. MUDr. L. Boudová, Ph. D.

Normal hemostasisThrombosis – factors, morphologyEmbolismShockDICTTP,HUS

Doc. MUDr. L. Boudová, Ph. D.

Page 3: Thrombosis Shock 2008. Normal hemostasis Thrombosis – factors, morphology Embolism Shock DIC TTP,HUS Doc. MUDr. L. Boudová, Ph. D.

Hemostasisnormal vesselsmaintain blood fluid, clot-freevessel injuryinduce rapid localized hemostatic plug

Thrombosisinappropriate activation of normalhemostatic processes

Vascular wall, platelets, coagulation cascade

Page 4: Thrombosis Shock 2008. Normal hemostasis Thrombosis – factors, morphology Embolism Shock DIC TTP,HUS Doc. MUDr. L. Boudová, Ph. D.

EndotheliumNormal: antithrombotic1. Anticoagulant - heparin-like moleculesthrombomodulin2. Antiplatelet – barrier between plt and ECM;

PGI2, NO, ADPase3. Fibrinolytic – t-PA

Injured, activated: prothrombotic1. Procoagulant – tissue factor2. Platelets - vWF3. Antifibrinolytic - PAI

Page 5: Thrombosis Shock 2008. Normal hemostasis Thrombosis – factors, morphology Embolism Shock DIC TTP,HUS Doc. MUDr. L. Boudová, Ph. D.

ThrombosisVirchow's 3Alteration of:

1. Vessel wall - endothelial injury - dominant

2. Blood flow- stasis, turbulence

3. Blood – hypercoagulability

may combine

intravital intravascularclotting

Page 6: Thrombosis Shock 2008. Normal hemostasis Thrombosis – factors, morphology Embolism Shock DIC TTP,HUS Doc. MUDr. L. Boudová, Ph. D.

1. Vessel wall – endothelial injury – dominant

exposure of subendothelial collagen + adherence of platelets

exposure of tissue factor, local depletion of prostacyclin and plasminogen activator

• Atherosclerosis – ulceration

• Necrosis – myocardial infarction

• Trauma

• Inflammation – vasculitis

• Hypertension, turbulent flow, bact. endotoxins

• Homocystein, cholesterol, radiation, smoking

Page 7: Thrombosis Shock 2008. Normal hemostasis Thrombosis – factors, morphology Embolism Shock DIC TTP,HUS Doc. MUDr. L. Boudová, Ph. D.

2. Alterations in normal blood flow

Normal = laminar

Turbulence – arteries, heart;

combined turb. + stasis (endot. injury + stasis)

Stasis – veins, heart

Ulcerated atherosclerotic plaques – endot. +turb.

Aneurysms – local stasis

Mitral valve stenosis – stasis – left atrial dilation

Hyperviscosity syndromes – polycythemia; sickle cell anemia (occlusions stasis; small vessels)

Page 8: Thrombosis Shock 2008. Normal hemostasis Thrombosis – factors, morphology Embolism Shock DIC TTP,HUS Doc. MUDr. L. Boudová, Ph. D.

3. Hypercoagulability

• Primary (genetic)

Mutations in factor V = Leiden mutation

2-15% of popul. APC resistance

antithrombin III, protein C, S deficiencies

fibrinolysis def., hyperhomocysteinemia

↑prothrombin levels - 1%, allelic variations

• Thrombo(embolism) – recurrent, young,

no or insignificant other causes

• Secondary (acquired) - high risk or low risk

Any alteration of coagulation pathway predisposing to thrombosis

Page 9: Thrombosis Shock 2008. Normal hemostasis Thrombosis – factors, morphology Embolism Shock DIC TTP,HUS Doc. MUDr. L. Boudová, Ph. D.

3. Hypercoagulability• Secondary (acquired)• ↑ High risk of thrombosis -immobilization, myoc.

infarction, tissue damage (trauma, burns, surgery), cancer, prosthetic cardiac valves, DIC, heparin-induced thrombocytopenia, antiphospholipid antibody syndrome (with/out autoimmune dis. - SLE)

• ↓Lower risk of thrombosis -atrial fibrillation, cardiomyopathy, nephrotic syndrome, hyperestrogenic states, oral contraceptives (3x), pregnancy (8x), sickle cell anemia, smokingThrombotic diathesis - often complicated, multifactorial

Page 10: Thrombosis Shock 2008. Normal hemostasis Thrombosis – factors, morphology Embolism Shock DIC TTP,HUS Doc. MUDr. L. Boudová, Ph. D.

Thrombi - overview of morphology, localisationrelationship to the vessel wall, lumen

mural OR occlusive; line of attachmentlocalization anywhere - heart (chambers, valves), arteries,

veins, capillariessizes, shapes, components (colours)

red, white, mixed (coral), hyalinemechanismarteries, heart: endothelial injury, turbulenceveins: stasis

Page 11: Thrombosis Shock 2008. Normal hemostasis Thrombosis – factors, morphology Embolism Shock DIC TTP,HUS Doc. MUDr. L. Boudová, Ph. D.

Thrombi

Localization - detailed

Arterial – occlusive; mixed

coronary, cerebral, femoral

atherosclerosis, vasculitis, trauma

Venous – occlusive, long cast; red; 90% legs

autopsy dif. dg. postmortem clot

Heart – valves – vegetations

infective or sterile (rheum., NBTE, SLE)

Heart chambers, aneurysms of heart or aorta

Mural; infarction; embolisation: brain, kidney, spleen

Page 12: Thrombosis Shock 2008. Normal hemostasis Thrombosis – factors, morphology Embolism Shock DIC TTP,HUS Doc. MUDr. L. Boudová, Ph. D.

Further fate of thrombi1. Propagation2. Dissolution - fibrinolysis3. Organization and recanalization; fibrosis4. Enz. digestion Puriform. degen.5. !Embolization!6. Calcification

1

2 35

7. Infection

Page 13: Thrombosis Shock 2008. Normal hemostasis Thrombosis – factors, morphology Embolism Shock DIC TTP,HUS Doc. MUDr. L. Boudová, Ph. D.

Clinical significance of thrombosis1. Vascular obstruction (mainly arteries)2. Source of embolism (mainly veins)

Veins: mainly lower extremitiesSpf.: trophic changes - cong., edem., pain; ulcersDeep: 50% asympt.! thromboembolism!

Regardless specific clinical setting: high age immobilization

!high risk of venous thrombosis!

Page 14: Thrombosis Shock 2008. Normal hemostasis Thrombosis – factors, morphology Embolism Shock DIC TTP,HUS Doc. MUDr. L. Boudová, Ph. D.

Embolisma detached intravascular mass- solid, liquid, gaseous carried by the blood to a site distant from its origin• Thrombus – 99%• Fat• Gas• Fluid – amniotic; • Atherosclerotic debris, tumor fragments, foreign bodies

VASCULAR BLOCK (ISCHAEMIA INFARCTION)

Page 15: Thrombosis Shock 2008. Normal hemostasis Thrombosis – factors, morphology Embolism Shock DIC TTP,HUS Doc. MUDr. L. Boudová, Ph. D.

SOURCE: DEEP LEG VEIN THROMBI

ABOVE THE KNEE

Clinical manifestation

1. Clin. silent (75%), organization, fibrous bridging web

2. Acute cor pulmonale – sudden death (60% circ.)

3. Pulmonary hemorrhage/infarction

4. Pulmonary hypertension (multiple emb.)

Pulmonary thromboembolism

Saddle embolusParadoxical embolism

Page 16: Thrombosis Shock 2008. Normal hemostasis Thrombosis – factors, morphology Embolism Shock DIC TTP,HUS Doc. MUDr. L. Boudová, Ph. D.

Systemic thromboembolismEmboli travelling in the syst. arterial circulation

• SOURCE: intracardiac mural thrombi (80%)aort. aneurysms, atherosclerotic plaques, valvular vegetations; paradoxical emboli

• RECIPIENTS: variouslegs (75%), brain (10%), intestines, kidneys, spleen, upper extr.

• CONSEQUENCES: collateral blood supply, tissue vulnerability to ischaemia, size of the occluded vessel MAINLY INFARCTION

Page 17: Thrombosis Shock 2008. Normal hemostasis Thrombosis – factors, morphology Embolism Shock DIC TTP,HUS Doc. MUDr. L. Boudová, Ph. D.

Fat embolism• fractures of long bones, soft tissue trauma, burns90% of people with severe skeletal injuriesonly 10% symptomatic

• sudden onset: tachypnea, dyspnea, tachycardia, neurol. symptoms, petechiae; (thrombo, ery ↓)

• mechanical and biochemical injury• may be lethal

• HISTOLOGICAL DIAGNOSIS ?

Page 18: Thrombosis Shock 2008. Normal hemostasis Thrombosis – factors, morphology Embolism Shock DIC TTP,HUS Doc. MUDr. L. Boudová, Ph. D.

Air embolismGas bubbles

• Obstetric procedures• Dural venous sinuses• Neck, chest wall trauma

• Decompression sickness - nitrogen bubbles focal ischemia: muscles, joints – bends; brain, heart;lungs - RDS (chokes)treatment: compression chamber

• Chronic decompression sickness – caisson diseasepersistence of gas emboli – multiple foci of ischemic necrosis(heads of femur, tibia, humerus)

Page 19: Thrombosis Shock 2008. Normal hemostasis Thrombosis – factors, morphology Embolism Shock DIC TTP,HUS Doc. MUDr. L. Boudová, Ph. D.

Amniotic fluid embolism• Rare but ! High mortality• Mechanism: amniotic fluid in maternal circulation

How: tear in the placental membranes, rupture of uterine veins

• Mother: lungs: diffuse alveolar damagecapillaries: epithelial squamous cells from fetal skin, lanugo hair, fat from vernix caseosa, mucin from fetal respiratory tract and GIT

• Clinically: sudden; severe dyspnea, cyanosis, hypotension, shock, seizures, coma; pulmonary edema, DIC (thrombogenic substances from amniotic fluid);death

Page 20: Thrombosis Shock 2008. Normal hemostasis Thrombosis – factors, morphology Embolism Shock DIC TTP,HUS Doc. MUDr. L. Boudová, Ph. D.

SHOCKSystemic hypoperfusion

caused by reduction of cardiac output effective circulating blood volume

hypotension, hypoperfusion, hypoxia

Cellular injury: first reversible

if persistence of shock - irreversible

Page 21: Thrombosis Shock 2008. Normal hemostasis Thrombosis – factors, morphology Embolism Shock DIC TTP,HUS Doc. MUDr. L. Boudová, Ph. D.

1. Cardiogenic – pump failure (intrinsic myoc. cause – IM, ventr. arrhytmias, extrinsic compression – tamponade, outflow obstr.- emb.)

2. Hypovolemic - loss of blood or plasma (hemorrhage, burns, trauma)

3. Septic – systemic microbial infection

(G- endotoxic, G+, fungal)

4. Neurogenic – spinal cord injury - VSD

5. Anaphylactic – gener. IgE-med. response, VSD, ↑vascular permeability – ↑vascular bed capacitance

SHOCK

Page 22: Thrombosis Shock 2008. Normal hemostasis Thrombosis – factors, morphology Embolism Shock DIC TTP,HUS Doc. MUDr. L. Boudová, Ph. D.

Pathogenesis of septic shockMost G-, endotoxins – lipopolysaccharides

Mononuclear cell activation, cytokines (IL-1, TNF)

Isolate microbes, activate immune system, eradicate microbes but also! further aggravation

cytokines and secondary mediators:

systemic VSD - hypotension,↓myoc. contractility,

↑endothel. injury, RDS, coagulation disorder – DIC

multiorgan system failure

Page 23: Thrombosis Shock 2008. Normal hemostasis Thrombosis – factors, morphology Embolism Shock DIC TTP,HUS Doc. MUDr. L. Boudová, Ph. D.

Stages of shock

1. Nonprogressive – neurohumoral compensatory mechanisms, vital organ perfusion

2. Progressive – tissue hypoperfusion, anaerobic glycolysis, lactate acidosis, VSD, ↓cardiac output, anoxic injury of endothelium, DIC risk; vital organs begin to fail

3. Irreversible – lysosomal enzyme leakage

Page 24: Thrombosis Shock 2008. Normal hemostasis Thrombosis – factors, morphology Embolism Shock DIC TTP,HUS Doc. MUDr. L. Boudová, Ph. D.

Morphology of shock

Hypoxic injury, multiple organ systems

Brain - ischemic encephalopathy

Heart - coagulation necrosis, hemorrhage

Kidneys - acute tubular necrosis

Lungs - shock lung (normally resistant to hypoxia)

Adrenals - cortical lipid depletion

GIT - hemorrhages and necroses

Liver - fatty change, central hemorrhagic necrosis

Page 25: Thrombosis Shock 2008. Normal hemostasis Thrombosis – factors, morphology Embolism Shock DIC TTP,HUS Doc. MUDr. L. Boudová, Ph. D.

secondary complication

of some serious condition consumption coagulopathy

thrombohemorrhagic diathesis

acute, subacute, chronic

Disseminated intravascular coagulation (DIC)

Page 26: Thrombosis Shock 2008. Normal hemostasis Thrombosis – factors, morphology Embolism Shock DIC TTP,HUS Doc. MUDr. L. Boudová, Ph. D.

Disseminated intravascular coagulation (DIC)

activation of coagulation sequence

microthrombi

- consumption of platelets and clotting factors

activation of fibrinolysissecondary

Page 27: Thrombosis Shock 2008. Normal hemostasis Thrombosis – factors, morphology Embolism Shock DIC TTP,HUS Doc. MUDr. L. Boudová, Ph. D.

DIC Thrombotic and hemorrhagic diathesis

Microthrombi infarctions

depletion of platelets and clotting factors

+ secondary activation of fibrinolysis

hemorrhages

Consequences

Page 28: Thrombosis Shock 2008. Normal hemostasis Thrombosis – factors, morphology Embolism Shock DIC TTP,HUS Doc. MUDr. L. Boudová, Ph. D.

Mechanisms of DIC trigger

1. Release of tissue factor or thromboplastic substances

2. Widespread endothelial injury

Page 29: Thrombosis Shock 2008. Normal hemostasis Thrombosis – factors, morphology Embolism Shock DIC TTP,HUS Doc. MUDr. L. Boudová, Ph. D.

DIC

1. obstetrics – 50%; abruptio placentae, retained dead fetus, septic abortion, amniotic fluid embolism, toxemia

2. neoplasms – 30%; adenocarcinomas, AML

3. infections – gram-negative sepsis

4. trauma, burns, extensive surgery

5. other – snakebite, heat stroke, giant hemangioma, aortic aneurysm etc.

Page 30: Thrombosis Shock 2008. Normal hemostasis Thrombosis – factors, morphology Embolism Shock DIC TTP,HUS Doc. MUDr. L. Boudová, Ph. D.

DIC• Morphology microthrombi

• kidneys hemorrhages

• lungs

• brain

• adrenals

• placenta

CLIN.: microangiopathic hemol. anemia, RDS, neurologic sympt., oliguria, ac. ren. and circul. failure, SHOCK

Page 31: Thrombosis Shock 2008. Normal hemostasis Thrombosis – factors, morphology Embolism Shock DIC TTP,HUS Doc. MUDr. L. Boudová, Ph. D.

Thrombotic microangiopathiesthrombotic thrombocytopenic purpura (TTP)hemolytic-uremic syndrome (HUS)

VersusDisseminated intravascular coagulation

Common: hyaline thrombi

!!Differences: DIC: primary importance:

activation of clotting system

Page 32: Thrombosis Shock 2008. Normal hemostasis Thrombosis – factors, morphology Embolism Shock DIC TTP,HUS Doc. MUDr. L. Boudová, Ph. D.

Thrombotic microangiopathiesrelated clinical syndromesthrombotic thrombocytopenic purpura (TTP)hemolytic-uremic syndrome (HUS)

ENDOTHELIAL INJURY WIDESPREAD HYALINE MICROTHROMBI

OVERLAP - common features (TTP, HUS):

• thrombocytopenia

• microangiopathic hemolytic anemia

• fever

Page 33: Thrombosis Shock 2008. Normal hemostasis Thrombosis – factors, morphology Embolism Shock DIC TTP,HUS Doc. MUDr. L. Boudová, Ph. D.

Thrombotic microangiopathies

TTP

neurological deficits (transient)

renal failureadult womenADAMTS 13 defic.

HUS

mostly no neurol. sympt.acute renal failure DOMINANT!children; E. coli O157:H7, verotoxin

Common: thrombocytopenia, microangiopathic hemolytic anemia, fever