Thrombosis, Embolism and Shock

Professor Arundathi P. KurukulasuriyaMBBS, Dip.Path,MD(Haem),FRCPA, AS THE, SFSEDA

Fluid Homeostasis

Cells and tissues need oxygen, removal of waste material and also an intact vascular system which carries these to and fro.

Normal fluid homeostasis needs

Normal :

• vessel wall

• Intravascular pressure

• osmolarity

Altered Fluid Homeostasis

Increased movement of water across the vessel wall is caused by :

Abnormal

• vessel wall/ function

• Intravascular pressure

• Osmolarity

It is called ‘oedema’

Oedema

Increased movement of water across the vessel wall in to interstitial spaces

Swelling of legs : Oedema of lower limbs

In the lungs : Pulmonary Oedema

In the peritoneal cavity : Ascites

In the thoracic cavity: Hydrothorax

HYPERAEMIA AND CONGESTION

Hyperaemia: AUGMENTED BLOOD FLOW DUE TO ARTERIOLAR DIALATATION

• Exercise

• Inflammation

Congestion :

Passive process. Collection of blood in vasculature due to poor venous return (has a cyanotic tinge)

*What is the colour of cyanosis? Why?

Congestion in Organs

Lungs : In Left ventricular failureAcute

Capillaries engorged with blood, focal intra alveolar haemorrhage, alveolar septal oedema

Chronic

Alveolar septa are thickened, fibrotic, Haemosiderin laden macrophages maybe present.

What are these haemosiderin laden macrophages called?

“Heart Failure cells”

Why are they laden with haemosiderin?

Engulf extravasated red cells in the alveoli

acute

chronic

Congestion in Organs cont…

Centrilobular necrosis -

Central vein with necrosis

of cells around it caused by

passive congestion in

hepatic vein

Liver : Macroscopy and microsdcopy

Why is it called the ‘nutmeg’ (Saddika)

appearance of liver?

Some Definitions

• Transudate:

• Fluid which leaks out due to increased hydrostatic pressure. Spg 1.012

• Exudate :

Fluid leaks out due to inflammation associated with increased vascular permeability, is protein rich

Spg 1.012

Nephrotic syndrome

Liver cirrhosis

Protein malnutrition

How does this cause oedema??

Low Albumin causes

low intravascular osmotic

pressure

Fluid moves out in to

interstitial tissue

capillaries

List conditions where there is

low Albumin in the body

Lymphatic Obstruction

Localised :

Filariasis

Ca breast post surgical removal of lymph nodes

What is ‘Paud o’ range’ ??

Paud o’ range appearance

due to tethering of skin in

lymphoedema

Pathophysiologic Categories of oedema

• Increased Hydrostatic Pressure• Impaired venous return • Congestive heart failure• Constrictive pericarditis• Ascites (liver cirrhosis)• Venous obstruction or compression Thrombosis• External pressure (e.g., gravid uterus, enlarged lymph

node)• Lower extremity inactivity with prolonged dependency• Arteriolar dilation • Heat• Neurohumoral dysregulation

Pathophysiologic Categories of oedema Cont…

• Reduced Lymphatic Obstruction

• Inflammatory

• Neoplastic

• Postsurgical

• Postirradiation

Pathophysiologic Categories of oedema

Plasma Osmotic Pressure (Hypoproteinemia)

• Protein-losing glomerulopathies (nephrotic syndrome)

• Liver cirrhosis (ascites)

• Malnutrition Protein-losing gastroenteropathy

Pathophysiologic Categories of oedema

Sodium Retention

• Excessive salt intake with renal insufficiency Increased tubular reabsorption of sodium Renal hypoperfusion

• Increased renin-angiotensin-aldosterone secretion

Pathophysiologic Categories of oedema

Inflammation

• Acute inflammation

• Chronic inflammation

• Angiogenesis

Quiz Time

Give yourself 1 mark for answering correctly

• What is the oedema of peritoneal space of abdomen called?

Ascites

• In the lung parenchyma?

Pulmonary oedema

• In encephalitis which organ may show odema?

Brain

Quiz Time

• Where would you expect oedema to occur in congestive cardiac failure?

• Dependent lower extremities

• In renal failure?

• Areas with loose subcutaneous connective tissue ie. peri orbital tissue

What’s your score??

Maintaining Blood In It’s Fluid State; What happens when it’s not

maintained• Thrombosis : inappropriate clotting in the

living body

• Migration of clots to distant sites : embolisation

• Obstruction of blood flow to tissues causing cell death: infarction

• Inability to clot when necessary leads to: haemorrhage

• Extensive haemorrhage may result in : Shock

Quiz Time Cont…

1. Define ‘oedema’

2. Classify the different mechanisms / aetiology of oedema

3. Draw a diagram of the circulatory system and explain how fluid homeostasis is maintained

List three main causes of haemodynamic disorders associated with high mortality in the western

world

1. Myocardial infarction

2. Pulmonary embolism

3. Cerebrovascular accidents

Normal Haemostasis

Fluid blood within the vascular system poised to clot rapidly at focal points of vascular injury, when necessary

Rudolf Virchow

German Pathologist

Virchow Triad

Axial (Laminar) Flow in Blood Vessels

Vascular Endothelium

Platelets and white

blood cells

Plasma layer between cells in

axial stream and the endothelium

What Disturbs The Laminar Flow?

• Stasis

• Turbulance

What Happens When Laminar Flow Is Disturbed?

1. Platelets come in contact with vessel wall

2. Prevent dilution of activated clotting factors

3. Retard inflow of anti thrombotic factors

4. Promote endothelial cell activation

What Factors Injure The Endothelium

Direct injury especially in the heart & arterial system:

Scars from myocardial ischaemia

Damaged valves

Atheromatous plaques

Vasculitis

What Factors Injure The Endothelium Cont…

• Haemodynamic stress of hypertension

• Bacterial endotoxins

• Hypoxia

• Homocystinuria

• Hypercholesterolemia

Protective Mechanisms To Prevent Thrombosis

• Axial flow

• Intact Endothelium

• Inactive clotting Factors

• Inert Platelets

• Inert prothrombotic pathways

• Normal fibrinolysis

Thrombosis

Inappropriate activation of haemostatic mechanism leading to clot formation in the living body

Ie. in uninjured /injured vasculature

• HITTS (Heparin induced thrombosis, thrombocytopenia syndrome)

• Lupus anticoagulant induced thrombosis

• AV fistulae

Thrombus

A mass formed from constituents of blood, within the vascular system, in the living body

Primary Haemostasis• Vascular injury

• Exposure of subendothelium to platelets

• Tissue Factor (TF)release**

• Platelets are activated shape change

• Platelet adhesion aggregation

• Platelet plug formation (white clot)

Primary haemostatic plug forms

*Arterial system favour white thrombi formation due to high shear rates

Normal Haemostasis

Properties of Vascular Endothelium

Related To Haemostasis

Thrombus Formation

Types of Thrombi

Red• In the venous circulation

• Contains fibrin, more red cells and platelets

• Forms in conditions where stasis of blood flow occurs

White• Arterial circulation

• Consists mainly of platelets and fibrin

• Forms because it is in high shear rate flow

Formation of a red thrombus

Columns of Zahn

Identify the different

structures

This vessel has an acute thrombus

with some faint lines of Zahn (platelet-

fibrin columns (arrow)), transmural

arterial inflammation

Columns of Zahn in a thrombus

What is this thrombus called?

Where in the circulation do they form more often?

Activated Platelets

Mind Map

Fate of A Thrombus

• Propagation along vessel in the direction of blood flow

• Embolisation

• Organization

• Recanalisation

• Dissolution

Fate of A Thrombus

Embolus

Is detached intravascular solid, liquid, or gaseous mass that is carried by the blood to a site distant from its point of origin

Thrombus

formation

How an embolus

forms

Types Of Embolisation

• thrombotic

• Fat

• Amniotic

• Air

Pulmonary Embolism

• Emboli commonly arise in the veins above knee in the lower limbs

• Most emboli are small and resolve

• Are large and block arterioles

• When 60% or more of the circulation is obstructed sudden death, cardiac failure may ensue

• Multiple emboli over a period of time cause pulmonary hypertension

Fat Embolism

• Occurs with fractures of long bones /Soft tissue injury

• Occurs about 1-3 days after injury

• Tachypnoea, dyspnoea, confusion, irritability purpura, thrombocytopenia and anaemia

( Symptoms related to CNS, RS, Blood)

Fat Embolism

Peticheal

Haemorrhages

Fat Embolism In The Brain

Air Embolism

• May occur during obstetric procedures

• Chest wall injuries

• Decompression sickness *

• >100cc of air is required to make any impact

* When gas dissolves under high pressure like in deep sea divers and IF they ascend fast to the surface(depressurising) the nitrogen bubbles out of solution and form gas bubbles

Home Work : Read ‘Caisson Disease’

Air Embolism Cont…

• Rapid formation of gas bubbles within the vessels of skeletal muscles cause pain

• Arch their backs – ‘bends’

• Focal ischaemia results in the brain, heart, in the lung focal haemorrhagic points may occur

• Treatment: compression chamber where the gas forced back in to solution and then allowed to dissolve out slowly instead of rapidly forming air bubbles

Amniotic Fluid Embolism

• Occurs during labour and immediate post partal period

• Mortality 20 - 40%

• sudden severe dyspnoea, cyanosis, hypotensive shock, followed by seizures and coma. If the patient survives the initial crisis, pulmonary edema typically develops, along with (in half the patients) DIC, owing to release of thrombogenic substances from amniotic fluid.

Squames

Amniotic fluid embolism

Amniotic Fluid Embolism Cont…

• Aetiology:

• Infusion of amniotic fluid or fetal tissue into the maternal circulation via a tear in the placental membranes or rupture of uterine veins.

• The classic findings : the presence in the pulmonary microcirculation of squamous cells shed from fetal skin, lanugo hair, fat from vernix caseosa, and mucin derived from the fetal respiratory or gastrointestinal tract.

Amniotic Fluid Embolism Cont…

• marked pulmonary edema and changes of diffuse alveolar damage

• systemic fibrin thrombi indicative of DIC.

Clinical Correlation

Emboli in the arterial system

cause ischaemia

Infarcts in brain, myocardium etc

Emboli in the venous system

Pain, swelling, tenderness, decolourisation of skin etc due to stasis and congestion.

Clinical Correlation Cont…

What is Deep Vein Thrombosis(DVT) ?

Superficial Vein Thrombosis(SVT) ?

When is DVT likely to occur?

Give reasons

Secondary Haemostasis

Formation of fibrin clot (red thrombus)

• Coagulation cascade

• Antifibrinolytic pathway

In the venous system ‘red thrombi’ formation occurs

Hypercoagulable States Primary (Genetic)

Common

• Factor V Leiden

• Prothrombin gene mutation

Rare

• Protein C, S deficiency

• Anti thrombin deficiency

Very Rare

• Defects in fibrinolysis

Hypercoagulable Statessecondary (Acquired) High Risk

• Prolonged bed rest

• Surgery, fracture, burns

• Myocardial infarction

• Prosthetic cardiac valves

• Cancer

• Lupus anticoagulant

• Antiphospholipid antibody syndrome

• HITTS (heparin induced thrombocytopenia thrombosis syndrome)

Hypercoagulable Statessecondary (Acquired) Low Risk

• Pregnancy

• cardiomyopathies

• Oral contraceptive use

• Nephrotic syndrome

• Treatment with cytarabine in acute leukaemia

Effects of Thrombi

• Reduces blood flow to organs

• Embolisation

Difference Between Thrombus and A Postmortem Clot

Thrombus• Forms in the living body

• Is firmly lodged on the endothelial surface

• Columns of Zahn* can be seen microscopically

Postmortem clot

• Forms in the dead body

• Can be dislodged easily, not attached to vessel wall

• Red cell precipitate to the bottom and chicken fat like jelly like plasma is on top

Coagulation

Cascade

Antifibrinolytic Pathway

Platelet

Activation

Blood vessel

constriction

Activation of

coagulation

cascade

Formation of

platelet thrombus

Fibrin Clot

Fibrinolysis

Physiological inhibitors of

coagulation and platelet

activation Inhibting factors

Vessel Injury

In a nut shell…

Defects in Coagulation Cascade

Haemorrhage

• Absence of

• defective function of coagulation factors

Thrombosis

• Activation of coagulation

• Reduced antithrombotic mechanisms

Clinical Conditions Caused By

Absence of Platelet Glycoproteins

Bleeding Disorders

Defects in :

• Coagulation

• Platelets

• Fibrinolytic Pathway

• Vascular endothelium

Hyphema commonly occurs

after trauma

A hyphema is an

accumulation of

blood in the anterior

chamber of the

eye. This is the

space between the

cornea (front clear

surface of the eye)

and iris (colored part

of the eye).

Commonly caused by vascular or platelet defects

1. Purpura

2. Petichiae

3. ecchymoses

Ecchymoses

Coagulation Defects

Haemarthrosis in weight bearing

joints in FVIII deficiency

( Haemophilia)

Queen victoria was a

carrier of

Haemophilia B

Haemophilia has featured prominently in European royalty and thus is

sometimes known as 'the royal disease'. Queen Victoria passed the

mutation for Haemophilia B to her son and, through some of her

daughters, to various royals across the continent, including the royal

families of Spain Germany and Russia. In Russia, Tsarevich Alexei

Nikolaevich son of Nicholas II was a descendant of Queen Victoria

through his mother Empress Alexandra and suffered from haemophilia.

Microangiopathic haemolytic

Anaemia : Disseminated

intravascular coagulation (DIC)

ecchymosis

Acquired haemophilia : Inhibitors to

FVIII molecule

Balance Between Thrombosis

and

Haemorrhage

THANK YOU