Transcript Document
The disorder of local
circulation
Dr. Philip S.L. Beh
Email:
[email protected]
Lecture Outline
Overview and revisit basic concepts
Circulatory system
Structure of blood vessels
Components of blood
Oedema
Generalised
Local
Effects on Brain and Lungs
Hemostasis – Normal physiological response
Thrombosis – Abnormal pathological response
Other forms of obstruction
Infarction – Abnormal pathological outcome
Overview and Revisit
Circulatory
System
Structure of blood vessels
Components of Blood
Circulatory System
– Pump
Blood Vessels – Pipes
Heart
Artery, Vein, Capillary
Lymphatics
– Drainage pipes
Properties of circulatory system
Ensure
smooth and adequate flow of
blood.
Delivers nutrients and oxygen
Removes waste and carbon dioxide
Properties of arteries
Aorta
Comes off the heart
Sustains high blood pressures
Elastic but rigid wall
Arteries
Lower blood pressures
Often have muscular wall and can contract
Structure of artery
Taken from www.sirinet.net/~jgjohnso/ circulation.html
Properties of veins
Thin
wall
Some have valves to prevent back-flow
of blood
Weak ability to contract even if there are
muscle fibers in the wall.
Dependant on “pumping action of
surrounding muscles – particularly of
the limbs.
Structure of vein
Taken from www.sirinet.net/~jgjohnso/ circulation.html
Properties of capillary bed
Very
thin wall often only one cell-thick and
can change to allow blood to pass through
into the interstitial space.
Taken from Underwood – General and Systemic Pathology
Taken from Guyton & Hall – Human
Physiology and Mechanisms of Disease
Properties of lymphatic
channels
Tube-like
Numerous
valves
Drains fluid back to blood-stream – passes
through at least one lymph-node.
Present in all tissues except
CNS, Eyeballs, Internal Ear, Epidermis of the
skin, cartilage and bone.
Taken from Guyton & Hall – Human Physiology and
Mechanisms of Disease
Systemic
circulation
vs.
Pulmonary
circulation
Taken from Robbins
Pathologic Basis of
Disease
Schematic of
lymphatic
channels
Taken from Colour Atlas of
Anatomy – Roden, Yokochi and
Lutjen-Drecoll
Components of Blood
– proteins, electrolytes and water
Cells – red blood cells, white blood cells
and platelets.
Plasma
Disorders of the Circulatory
System
Congestion
Hemostasis
Thrombosis
Emboli
Other
obstruction
Ischaemia and infarction
Congestion
Distension
of blood vessels
May be an active or passive process
Reversible condition
Oedema
Oedema
Water
compartments
Movement of water between the
compartments
Causes of oedema
Pulmonary oedema
Cerebral oedema
Taken from Guyton & Hall – Human Physiology and Mechanisms
of Disease
Taken from Underwood – General and Systemic Pathology
Taken from
Guyton & Hall –
Human Physiology
and Mechanisms
of Disease
Taken from
Guyton & Hall
– Human
Physiology
and
Mechanisms
of Disease
Taken from Guyton & Hall – Human
Physiology and Mechanisms of Disease
Taken from Guyton & Hall – Human Physiology and
Mechanisms of Disease
Taken from Guyton & Hall – Human Physiology and
Mechanisms of Disease
Taken from Guyton & Hall – Human Physiology and
Mechanisms of Disease
Taken
from
Guyton &
Hall –
Human
Physiology
and
Mechanis
ms of
Disease
Taken from Underwood – General and Systemic Pathology
Taken from Underwood – General and Systemic Pathology
Taken from Underwood – General and Systemic Pathology
Taken from Sternberg`s HISTOLOGY for PATHOLOGISTS
Taken from Sternberg`s HISTOLOGY for PATHOLOGISTS
Taken from Colour Atlas of
Anatomy – Roden, Yokochi
and Lutjen-Drecoll
Taken from Colour Atlas
of Anatomy – Roden,
Yokochi and Lutjen-
Taken from Colour
Atlas of Anatomy –
Roden, Yokochi
and Lutjen-Drecoll
Taken from
Colour Atlas of
Anatomy –
Roden, Yokochi
and LutjenDrecoll
Hemostasis
Diagram from Robbins Pathologic Basis of Diseases
Platelet adhesion to von
Willebrand’s factor
Diagram from Robbins Pathologic Basis of Diseases
Hemostasis – Adhesion and
Recruitment
Diagram from Robbins Pathologic Basis of Diseases
Hemostasis – Thrombin
activation
Diagram from Robbins Pathologic Basis of Diseases
Diagram from Robbins Pathologic Basis of Diseases
Hemostasis - Plug
Diagram from Robbins Pathologic Basis of Diseases
Opposing actions
Diagram from Robbins Pathologic Basis of Diseases
Thrombosis
Definition
– a blood clot.
Thrombosis – a pathological process
whereby there is formation of a blood clot
in uninjured vasculature or after
relatively minor injury.
Thrombus
Definition
– A detached intravascular solid,
liquid or gaseous mass that is carried by
the blood to a site distant from its point of
origin.
Embolus
Virchow’s Triad
Pathogenesis
of a
Thrombus
Endothelial injury
Abnormal blood flow
Hypercoagulability
• Primary (genetic)
• Secondary (acquired)
ENDOTHELIAL
INJURY
THROMBOSIS
ABNORMAL
BLOOD FLOW
HYPERCOAGULABILITY
Endothelial Injury
Dominant
factor
Sufficient as the sole factor
Examples include
Myocardial infarction
Ulcerated atheromatous plaques
Hemodynamic injury such as hypertension,
turbulent flow over heart valves
Endotoxins, inflammation, etc
Abnormal Blood Flow
Turbulence in arterial flow as a result of changes
in the diameter of the vessel leading to nonlaminar flow, resulting in:-.
Platelet coming into contact with endothelium.
Prevent dilution by fresh flowing blood of
activated clotting factors.
Retard inflow of clotting factor inhibitors.
Promote endothelial cell activation predisposing
to local thrombosis.
Hypercoagulability
Alteration
of the coagulation pathway
that predisposes to thrombosis
Higher viscosity of blood changing the
flow dynamics of blood
Fate of a Thrombus
Diagram from Robbins Pathologic Basis of Diseases
Fate of a Thrombus
The
thrombus may propagate
The thrombus may become organised and
recanalised
The thrombus may become organised and
incorporated into the wall of the vessel
The thrombus may be resolved completely
The thrombus may dislodge and become
an embolus or emboli
Propagation of Thrombus
Classification of Thrombi
Anatomical
Cardiac
Arterial
Venous
Capillary
Morphological
Pale (platelet
thrombus)
Red (RBC thrombus)
Mixed (intermittent
layers)
Renal
Artery
Thrombus
Iliac
Artery
Thrombosis of the
descending aorta
extending from the
origins of the renal
arteries down to the
iliac vessels
A mixed thrombus
Pale thrombus
Red thrombus
Venous Thrombosis
Two
distinct types
Phlebothrombosis – predisposes to
thromboemboli to lungs
Thrombophlebitis – unusual to have
associated pulmonary thromboemboli
Effects of Thrombosis
Dependent
on location and degree of
vascular occlusion.
Effects also dependent on the
availability of collateral blood supply
and susceptibility of area of supply to
interruption of blood supply.
Demand
Supply
Taken from www.ecureme.com/atlas/ ata/Renal_Artery_Steno...
Taken from Underwood – General and Systemic Pathology
Other obstruction
Atherosclerosis
Embolism
Others
Congenital
Mechanical
Chemical
Iatrogenic
Schematic of
atherosclerosis
Concepts of atherogenesis
Hyperlipideamia, Hypertension,
Smoking, Homocysteine,
Hemodynamic factors, etc
Endothelium (E)
Subendothelial space
Smooth muscle layer (S)
Endothelial
Injury/Dysfunction
Adventitia
Taken from Robbins Pathologic Basis of Disease
Concepts of atherogenesis
Circulating platelets
adhere to endothelial
surface
Leukocyte
adhesion
Leukocyte migration
Taken from Robbins Pathologic Basis of Disease
Concepts of atherogenesis
Endothelial
Permeability
increased
LDL, VLDL
and leukocyte
accumulation
Ingestion of oxidised
LDL by leukocyte
(Foamy macrophage)
Smooth muscle migration
Taken from Robbins Pathologic Basis of Disease
Concepts of atherogenesis
Gross appearance of
fatty streaking
Macrophage
and smooth
muscles
engulfing
more and
more LDL
Arrival of
lymphocyte
Taken from Robbins Pathologic Basis of Disease
Concepts of atherogenesis
Smooth muscle
proliferation
and
accumulating
extracellular
collagen and
fatty deposits
Effects of atherosclerosis
Hardening
of the wall,
Loss of elasticity
Obstruction of lumen
Aneurysm
Rupture
Markedly atheromatous
Advanced
atheromatous
and
calcified
aorta with
degeneration and
thrombus
saddle at the
calcification with thrombus
iliac
bifurcation.
at iliac
bifurcation
Cerebrovascular Disease
Intracerebral
haemorrhage with rupture
of the haemorrhage into
the lateral ventricle of the
brain. This lesion is likely
to result in hemiplegia
and could also be fatal if
the brain haemorrhage
and swelling cannot be
controlled.
Types of embolism
Pulmonary
Air
Fat
Amniotic
Septic
Tumour
Others
fluid
Emboli
Pulmonary
Fat
thromboemboli
emboli
Marrow emboli
Air emboli
Amniotic fluid emboli
Others – foreign bodies e.g. glass, metal
fragments (even occasionally bullets), etc.
Phlebothrombosis
Phlebothrombosis
Pulmonary
Thromboembolism
Probably
the most common form of
embolism.
Emboli derived from thrombosis of deep
veins of the lower limbs.
Predisposing factors include prolonged
immobility, dehydration, etc.
Fat Embolism
Commonly
found at autopsies
Often associated with injuries to
adipose tissues, long bones and
stressful states
May be quite asymptomatic
Can however lead to extensive
occlusion of vessels leading to
hemorrhagic infarcts
Marrow Embolism
Often
seen together with fat
embolism in particular
following fractures of long
bones.
Also quite commonly found
after fractures of ribs during
cardiopulmonary resuscitation.
Air-embolism
Associated with “high-pressure”
activities or work, e.g.. Scuba diving,
compression chamber workers, etc
Gases are dissolved in the blood at
high pressures, sudden
decompression allows the gases to
form bubbles within the vascular
system, leading to obstruction
Air-embolism
When
large quantities of gases/air
collects in the right heart (usually
more than 100 ml), the pumping
action of the heart together with the
blood plasma and air/gas mixture will
lead to frothing and obstruction to the
blood flow and death.
Amniotic Fluid Embolism
Associated with high mortality.
Contents of the fetal amniotic sac is
forced into the maternal circulation
often during induced labour.
The squames and other material in the
amniotic fluid is believed to lead to an
anaphylactic type reaction with
resultant disseminated intravascular
coagulopathy and death due to shock.
Embolism – other forms
A variety
of material may give
rise to emboli, e.g. Foreign
objects such as glass, bullets,
etc.
Tumor and bacteria may give
rise to tumor and septic emboli.
Effects of embolisation
Identical
to those of thrombosis
and governed by similar factors.
Effects of embolism
Dependant
on extent of disruption to the
local circulation and susceptibility of the
target organ or tissue to such disruption.
Fate of a Thrombus
Diagram from Robbins Pathologic Basis of Diseases
Tissues supplied by end-arteries
without significant collateral
supplies will be the most
susceptible.
Obstruction of blood supply
leads to ischemia which when
prolonged leads to necrosis and
atrophy.
Where there is reperfusion after
ischemic necrosis the tissues will
show a hemorrhagic necrosis.
Where there is infection by
Clostridia (gram positive bacilli),
gangrene sets in.
Ischaemia
Transient
Insufficient
blood supply
Infarction
Cell
death due to prolonged ischaemia
Irreversible
Mural
thrombus of the
left ventricle
commonly seen
after
transmural
infarction
Occlusive
thrombus or
emboli of cerebral
artery leading to
hemorrhagic
infarct of internal
capsule region
Chronic insufficient blood supply leading to atrophy
Patchy areas of gangrene of left foot
Bilateral gangrene of feet.
Wedged shaped area of infarct of the liver
Hemorrhagic infarcts of small bowels
Coil of thromboemboli of the pulmonary trunk
Saddle thrombus of the pulmonary trunk
Often leads to sudden death.
Pulmonary
thrombus –
organised
Hemorrhagic
infarcts of the
lung
Fat emboli stained red
Fat embolism involving
glomeruli of kidney
Marrow emboli
Amniotic fluid emboli (squames)
Tumor embolus
References
& Hall – Human Physiology and
Mechanisms of Disease – 6th Edition
Guyton
Section IV – Chapters 13
Section V – Chapters 20
– Pathologic Basis of Disease –
5th Edition
Robbins
Chapter 1V