Disturbances in circulation

Oedema

Thrombosis

Haemorrhage

Dr. Rod Suepaul

DVM, MVS, DACVP
School of Veterinary
Medicine
The University of the
West Indies
Oedema
• Tissue swelling due to excessive
accumulation of fluid in the interstitial
space
• ascites
• hydrothorax
• hydropericardium
• Anasarca
• https://www.youtube.com/watch?v=l1Nj
EoeXU2M
gross appearance of ascites
post-mortem appearance of ascites
Hydropericardium/pericardial effusion
subcutaneous
oedema
Development of oedema
• Blood- plasma and cells
• movement of fluid between vascular and
extravascular compartments depends on
balance of hydrostatic and osmotic pressure
• explained by Starling equilibrium
• under normal conditions some fluid moves out
of vessels at arterial end
• balanced by lymphatic drainage plus resorption
of fluid at venous end
HP

lymphatics
HP

lymphatics
HP

COP

lymphatics
Development of oedema...
• Oedema ensues when:
• excessive fluid movement out of vessels
• (note lymphatic drainage can increase markedly
to compensate)
• insufficient lymphatic drainage
 Pathophysiologic categories
(Mechanisms) of oedema
• increased hydrostatic
pressure
• decreased osmotic
pressure
• lymphatic blockage
• increased vascular
permeability –
inflammation
• Sodium/water retention
1.Increased hydrostatic
pressure
• increased pressure within capillaries
• venous pressure determines capillary
hydrostatic pressure
• may be local or systemic
• local:
• collapse of vessel due to external pressure eg
tourniquet, tumour, organ torsion
• Venous obstruction eg thrombus, tumour, lower
extremity inactivity (prolonged dependency)
strangulation of intestine
Increased hydrostatic pressure
• systemic (generalised)
• most common cause is congestive heart failure
• pathogenesis involves renin-angiotensin system
(secondary aldosteronism)
• main features:
• decreased cardiac output e.g. constrictive pericarditis
• blood shunted away from kidney
• decreased renal perfusion causes release of renin
• renin catalyses conversion of plasma angiotensinogen to
angiotensin I...
Pathogenesis of cardiac
oedema
• angiotensin I passes to lungs, converted to
angiotensin II
• passes to adrenal cortex - triggers aldosterone
release
• aldosterone stimulates sodium retention (renal
tubules)
• water retained along with sodium
• results in expansion of plasma volume and hence
increased venous pressure
Increased hydrostatic pressure

• Arteriolar dilation
• Heat
• Neurohumoral dysregulation
2. Decreased osmotic pressure
• albumin is most important osmotically
active substance in plasma
• hypoalbuminaemia may be due to:
• decreased formation (hepatic/starvation)
• increased loss(parasitism/ nephrotic
syndrome)
• sequestration
• because hypoalbuminaemia is systemic,
generalised oedema develops
Causes of hypoalbuminaemia

• decreased albumin synthesis

• decreased amino acid supply (starvation)
• severe hepatic disease (cirrhosis)
Causes of hypoalbuminaemia…

• increased albumin loss

• whole blood loss
• repeated haemorrhages
• gastrointestinal loss
• whole blood eg haemonchosis, gastric ulcers
• protein loss alone eg inflammation, PLEs
• nephrotic syndrome
 3. Lymphatic blockage
• causes localised oedema
• known as lymphoedema or lymphatic
oedema
• obstruction may be internal or external
• tumour invasion of regional lymph node
(breast cancer –overlying skin – orange
peel appearance)
• surgical removal of lymph nodes (breast
cancer –axillary LN)
• traumatic transection of lymphatics,
overtight bandaging, irradiation
Blockage of lymphatics
4. Increased vascular
permeability
• usually local
• most often results from inflammation
• inflammatory mediators cause increased
endothelial “leakiness”
• loss of fluid, cells, protein into tissues
• resulting high protein fluid known as
exudate
Sodium retention
• Contributes to other forms
• Water retained along with Na (salt)
• Increases hydrostatic pressure and
decreases colloid osmotic pressure
(dilution)
• Acute reduction in renal function –
glomerulonephritis and acute renal
failure
Examples of oedema
syndromes
• Nephrotic syndrome
• protein-losing nephropathies
• generally involve glomerular disease
• loss of albumin (lowest molecular weight
protein) causes hypoalbuminaemia
• sodium retention also plays a role
Examples...
• Hepatic disease
• often seen as ascites, esp if associated with
fibrosis (cirrhosis) - portal hypertension
• decreased protein (albumin) synthesis
central mechanism
• aggravated by decreased inactivation of
aldosterone
Examples...
• Pulmonary oedema
• left-sided heart failure causes backflow of
pressure into pulmonary vessels
• increased pulmonary hydrostatic pressure
results in transudate forming in alveoli
• may also occur due to endothelial damage by
inhaled irritants, anaphylaxis, acute
respiratory infections
• Humans- ARDS
• Lungs heavy, wet, blood tinged froth-
trachea
pulmonary oedema pulmonary effusion
Examples...
• Cerebral oedema
• no room for expansion
• causes clinical signs via pressure on brain
tissue
• oedematous brain is swollen, heavy, gyri
flattened, narrowed sulci
• Localised- brain tumours, head trauma,
abscessation etc
• Generalised- widespread endothelial
damage- encephalitis, hypertensive crisis,
trauma, obstruction of venous outflow
Gross appearance of oedema
• Humans- most common subcutis, lung and
brain
• solid tissues - wet, heavy, enlarged
• subcutaneous tissues
• distension, swelling
• pitting on pressure
• gravity-dependent eg bottle-jaw, brisket
• incised tissue may pour fluid
Morphology of oedema

• Severe generalised – anasarca

• Subcutis- diffuse/localised, dependent
(gravity) – legs/sacrum
• Humans- renal disease- all parts of body
equally e.g. loose ct- eyelids; cardiac-
dependent areas
• Pregnancy associated
• Legs- peripheral –pitting/non-pitting
pitting oedema…
…after
Clinical significance of oedema

• depends on:
• extent (volume of fluid)
• large volumes may act as space-occupying lesions
• duration
• chronic oedema may lead to fibrosis - impairs
function
• location (tissue affected)
• pulmonary or cerebral oedema may be fatal
TRANSUDATE VS EXUDATE
Transudate-
low protein, few cells,
increased hydrostatic pressure or decreased
osmotic pressure

Exudate
High protein, more cells
Inflammation- increased vascular
permeability or lymphatic onstruction
Disturbances in circulation

Thrombosis
Definitions and examples
• Solid mass/plug formed within the
circulatory system from components of
blood, formed during life
• most thrombi resolve uneventfully
• large vessel thrombosis
• microvascular
• eg coronary thrombosis
thrombosis (DIC)
Causes of thrombosis

•Virchow’s triad
Endothelial damage
• most important factor
• clot initiation
• may involve trauma,
inflammation, frost bite,
chemical irritants,
infectious agents
• activates clotting cascade
via intrinsic and extrinsic
pathways
 Endothelial disruption
• Exposure of sub-endothelial ECM,
platelet adhesion, release of tissue
factor, depletion of PGI2
Heart/arteries- normal flow rate
hamper platelet clot and dilute factors

• Alteration of endothelium with

myocardial infarction, ulcerated
atherosclerotic plaques, vasculitis
Endothelial factors
• Physical disruption not necessary
• Perturbation of pro and anti thrombotic
effects
• Increase procoagulant- platelet adhesion
molecules, tissue factor
• Reduced anticoagulant- thrombomodulin,
PGI2, t-PA
• Endothelial dysfunction- hypertension,
scarred valves, endotoxin,
hypercholesterolaemia, radiation,
cigarette smoke products
 Abnormal blood flow
• influences thrombus progression

• vascular stasis (eg in veins, aneurysms,

varicose veins)

• loss of laminar flow,

• Turbulence – pockets of stasis-

arteries
Abnormal blood flow

• Stasis and turbulence- prevent dilution

of activated clotting factors
• Retard inflow of clotting factor
inhibitors
• Promote endothelial activation
 Abnormal blood flow
• Local stasis/reduced flow- torsion,
volvulus, varicocoele, external
compression
• Anuerysm
• Hypovolaemia- shock, diarrhoea, burns
• Hyperviscosity syndromes- polycythaemia
• Sickle Cell Anaemia
Abnormal blood flow
• Cardiac disease- cardiomyopathy,
hypertrophy, region of non
contractile myocardium
• Valvular stenosis with atrial dilation,
endocarditis, ulcerated
atherosclerotic plaques
Abnormal blood composition

• Hypercoagulability – alteration in coagulation

pathway that predisposes to thrombosis
• influences thrombus progression
• clotting factors
• PCV (haemoconcentration eg dehydration)
• platelets
• misc (drugs, disease)
Hypercoagulability - Humans
Primary- genetic
• Most common - mutation in Factor V (resist
Protein C cleavage) and prothrombin
(elevated PT levels) genes
Secondary – acquired - multifactorial- with
stasis, vascular injury, immune reactions
• Increased hepatic synthesis of coagulation
factors and reduced ATIII synthesis –
(pregnancy, oral contraceptives)
• Disseminated cancers – procoagulant tumor
products
• Age, smoking, obesity
Formation of a thrombus

• occurs in layers
• platelets adhere to
damaged endothelium
Mural-attached-e.g.
heart chambers,
aorta
 Venous thrombi- cast of lumen,
firm red, attached e.g. – deep vein
thrombosis

Arterial thrombi
Laminated appearance
of a thrombus (“lines of
Zahn”). The darker
layers correspond with
increased numbers of
red cells trapped in a
mesh of fibrin (see
above). Laminated
thrombi usually form in
larger arteries
From Rubin, 1994
• multiple thrombi (human angiogram) partially obstructing
bloodflow
 Venous
thromboembolism
(VTE) – comprising
deep vein thrombosis
(DVT) and pulmonary
embolism (PE) – may
account for almost 2
million cases every year
in the U.S. Out of the
nearly 600,000 PE
cases, anywhere from
60,000 to 200,000
result in death each
year

lower limbs- deep calf veins

Fate of thrombi
• attached to endothelium:
• Lysis/dissolution by fibrinolysis
• Propagation- accumulate fibrin and
platelets- occlude lumen
• shrinkage and recanalisation
• Organisation with inflammation and fibrosis
• Embolism – dislodge and travel
• combinations
Disseminated intravascular
coagulation
• widespread clotting within the vascular
system
• results in multiple fibrin clots within
terminal vascular beds
• triggers fibrinolysis - resulting fibrin
degradation products (FDPs) inhibit
coagulation
 Haemorrhage
• Extravasation of blood usually from damaged
vessel
• often caused by trauma also inflammatory or
neoplastic erosion or atherosclerosis
• vascular disease may predispose to
haemorrhage
• local high blood pressure also predisposes
• diffuse haemorrhage may occur in coagulation
disorders
• Chronic congestion- capillary bleeding
 Haemorrhage - definitions
• diapedesis = loss of individual erythrocytes
between endothelial cells
• haematoma = local accumulation of blood, usually
clotted
• petechiae = pin-point 1-2mm haemorrhages
• Puppura- >=3mm
• ecchymoses = paintbrush > 1-2 cm haemorrhages
Causes

• Petechiae, purpura, ecchymoses-

increased intravascular pressure,
thrombocytopenia, defective platelet
function (uraemia), clotting factor
defects
• purpura, ecchymoses- trauma, vascultits,
vascular fragility (amyloidosis)
Colour changes
Rbcs phagocytosed-
Hb- red/blue
Bilirubin- blue-green
Haemosiderin-
gold/brown
petechiae and
ecchymoses
ecchymoses
 Local effects of
haemorrhage
• effect depends on location eg retina,
brain
• space-occupying lesions - eg pericardium,
lungs
• small haemorrhages - no residual effect
• larger haematomas - fibrosis,
haemosiderin in macrophages
 haemopericardium

Other cavities- haemothorax,

haemoperitoneum, haemarthrosis
retinal haemorrhage
intracerebral haemorrhage
increased intracranial pressure
-herniation
Gastric ulcers - melaena
 Systemic effects of haemorrhage
• depends on severity and speed of onset
• repeated minor bloodloss may lead to
iron deficiency (eg GI ulcers)
• acute bloodloss of less than 20% blood
volume - compensatory mechs sufficient
• acute bloodloss of 30% or more -
hypovolaemic shock likely
• slower loss of 30% - compensation may
be adequate
• Extensive – jaundice massive rbc
breakdown