Post on 27-Jan-2016
description
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