Haemodynamic disorders , thromboembolism and shock by Dr Nadeem (RMC)

HAEMODYNAMICHAEMODYNAMIC
DISORDERS,DISORDERS,
THROMBOEMBOLISMTHROMBOEMBOLISM
ANDAND
SHOCKSHOCK

HAEMODYNAMICHAEMODYNAMIC
CHANGESCHANGES
•• The health and well- being of cells and tissues dependsThe health and well- being of cells and tissues depends
upon:upon:
1. An intact blood circulation to deliver oxygen1. An intact blood circulation to deliver oxygen
2. Normal fluid homeostasis2. Normal fluid homeostasis
••The abnormalities in blood supply or fluid balance leads toThe abnormalities in blood supply or fluid balance leads to
different disorders like:different disorders like:
(i) Edema(i) Edema
(ii) Vascular Congestion(ii) Vascular Congestion
(iii) Hemorrhage(iii) Hemorrhage
(iv) Thrombosis(iv) Thrombosis
(v) Embolism(v) Embolism
(vi) Infarction(vi) Infarction
(vii) Shock(vii) Shock

• Thrombosis, embolism and InfarctionThrombosis, embolism and Infarction
underlie three most impotent causes ofunderlie three most impotent causes of
morbidity and mortality in Western societymorbidity and mortality in Western society
• For example:For example:
-Myocardial Infarction-Myocardial Infarction
- Cerbrovascular accident- Cerbrovascular accident
- Stroke- Stroke

HYPEREMIAHYPEREMIA
ANDAND
CONGESTIONCONGESTION

HYPEREMIA ANDHYPEREMIA AND
The term hyperemia and congestion indicate aThe term hyperemia and congestion indicate a locallocal
increased volume of blood in a particularincreased volume of blood in a particular
tissuetissue
HYPEREMIAHYPEREMIA
It is anIt is an Active ProcessActive Process resulting fromresulting from
increased tissue inflow because of arteriolar dilation, asincreased tissue inflow because of arteriolar dilation, as
in skeletal muscle during exercise, or at sites inin skeletal muscle during exercise, or at sites in
inflammation.inflammation.
The effected tissue is redder because of theThe effected tissue is redder because of the
engorgement with oxygenated bloodengorgement with oxygenated blood

It is aIt is a Passive ProcessPassive Process resulting from impairedresulting from impaired
outflow from a tissue. It may occur systemically oroutflow from a tissue. It may occur systemically or
locally.locally.
•• Systemic Congestion:Systemic Congestion: As in cardiac failureAs in cardiac failure
•• Local Congestion:Local Congestion: As in isolated venous obstructionAs in isolated venous obstruction
In congestion tissue has a blue red colourIn congestion tissue has a blue red colour
((CyanosisCyanosis)) particularly as worsening congestion leads toparticularly as worsening congestion leads to
accumulation of deoxygenated hemoglobin in theaccumulation of deoxygenated hemoglobin in the
affected tissues.affected tissues.
Congestion of capillary beds is closely related to theCongestion of capillary beds is closely related to the
development of edema, so that congestion and edemadevelopment of edema, so that congestion and edema
commonly occur togethercommonly occur together

HYPEREMIAHYPEREMIA CONGESTIONCONGESTION
Active processActive process Passive processPassive process
Results from increasedResults from increased
tissue inflow due totissue inflow due to
arteriolar dilatationarteriolar dilatation
Results from impaired outResults from impaired out
flow from a tissueflow from a tissue
Effected tissue is redEffected tissue is red
because of the engorgementbecause of the engorgement
with oxygenated bloodwith oxygenated blood
Effected tissue is bluish –Effected tissue is bluish –
red due to accumulation ofred due to accumulation of
deoxygenated blood.deoxygenated blood.
Will lead to Erythema Will lead to Cyanosis
Examples: (i) In skeletal
muscle during exercise ; (ii)
At sites of inflammation
Example: (i) Systemic: As in
congestive cardiac failure ;
(ii) Local: As in isolated
venous obstruction
Hyperemia Vs CongestionHyperemia Vs Congestion

Hyperemia Vs Congestion
In both cases there is an increased
volume and pressure of blood in a
given tissue with associated capillary
dilation and a potential for fluid
extravasation.
In Hyperemia: increased inflow leads to
engorgement with oxygenated blood,
resulting in erythema
In Congestion: diminished outflow leads
to a capillary swollen with deoxygenated
venous blood and resulting in cyanosis

MORPHOLOGIC CHANGES IN HYPEREMIAMORPHOLOGIC CHANGES IN HYPEREMIA
AND CONGESTIONAND CONGESTION
GROSS EXAMINATIONGROSS EXAMINATION:: Cut surface of hyperemic or congestedCut surface of hyperemic or congested
tissue area haemorrhagic and wet.tissue area haemorrhagic and wet.
MICROSCOPIC EXAMIANTIONMICROSCOPIC EXAMIANTION::
a)a) Pulmonary CongestionPulmonary Congestion::
(i)(i) Acute Pulmonary CongestionAcute Pulmonary Congestion: Alveolar capillaries are: Alveolar capillaries are
engorged with blood. There may be associated alveolar septalengorged with blood. There may be associated alveolar septal
edema or focal intra alveolar hemorrhage.edema or focal intra alveolar hemorrhage.
(ii)(ii) Chronic Pulmonary CongestionChronic Pulmonary Congestion: The septa have become: The septa have become
thickened and fibrotic. The alveolar spaces may containthickened and fibrotic. The alveolar spaces may contain
numerous hemosidrin laden macrophagesnumerous hemosidrin laden macrophages ((Heart FailureHeart Failure
Cells)Cells)
b)b) Congestion of LiverCongestion of Liver:: The central regions of the hepatic lobulesThe central regions of the hepatic lobules
are grossly red brown and slightly depressed due to loss of cellsare grossly red brown and slightly depressed due to loss of cells
and are accentuated against the surrounding zones ofand are accentuated against the surrounding zones of
uncongested liveruncongested liver( nutmeg liver)( nutmeg liver) .(.(so called because itso called because it
resembles the alternating pattern of light and dark seen when aresembles the alternating pattern of light and dark seen when a
whole nutmeg is cut) In long standing congestion due to cardiacwhole nutmeg is cut) In long standing congestion due to cardiac
failure there can be hepatic fibrosisfailure there can be hepatic fibrosis ((Cardiac CirrhosisCardiac Cirrhosis))

Heart Failure CellsHeart Failure Cells
Haemosidrin laden macrophages seen in alveolarHaemosidrin laden macrophages seen in alveolar
spaces, in pulmonary congestionspaces, in pulmonary congestion
Nutmeg liverNutmeg liver
Alternating pattern of lightAlternating pattern of light
and dark areas seen inand dark areas seen in
congestion of liver (resemblescongestion of liver (resembles
alternating dark and light when a whole nutmegalternating dark and light when a whole nutmeg
is cut)is cut)
CCardiac Cirrhosisardiac Cirrhosis
Hepatic fibrosis seen in chronic heart failureHepatic fibrosis seen in chronic heart failure

Liver with Chronic Passive Congestion and
Haemorrhagic Necrosis
A: Central areas are red and slightly
depressed compared with the
surrounding tan viable parenchyma,
forming a “nutmeg liver” pattern
(so called because it resembles
the alternating pattern of light and
dark seen when a whole nutmeg
is cut
B: Centrilobular necrosis with
degenerating hepatocytes and
haemorrhage

 Left-sided heart failureLeft-sided heart failure
 chronic congestion of lungchronic congestion of lung
 lung edema, haemorrhage:lung edema, haemorrhage: weightweight
increased, sogginess subcrepitant, sectioningincreased, sogginess subcrepitant, sectioning
permits the free escape of a frothy hemorrhagicpermits the free escape of a frothy hemorrhagic
fluid,fluid,
 Microscope showed alveolar walls are dilated andMicroscope showed alveolar walls are dilated and
alveolar space edema,full with red cells and canalveolar space edema,full with red cells and can
findfind ““heart failure cell””
brown induration of the lungbrown induration of the lung


““HHeart failure cell”eart failure cell” macrophagesmacrophages
phagocytose red cellphagocytose red cell
then the red cell break downthen the red cell break down
intointo hemosiderin granuleshemosiderin granules

Acute congestion of the lung with pulmonary edema. Chronic congestion with heart failure
cells

Right-Sided Heart FailureRight-Sided Heart Failure
Nutmeg liverNutmeg liver:Liver congestion in centrilobular:Liver congestion in centrilobular
areas surrounded by fatty degenerationareas surrounded by fatty degeneration
peripheral regionsperipheral regions
cardiac sclerosiscardiac sclerosis
persistence

Nnutmeg liver (photo is offered by )
Histologic appearance of
atrophy and necrosis of cells
in the central part of the liver
lobule in chronic congestion

Chronic venous congestion ( nutmeg liver)

Chronic venous congestion ( nutmeg liver) with recent infarction

Section in the lung shows
Thickened alveolar wall with
congested dilated alveolar
capillaries. The alveolar
spaces contain intact and
haemolysed red blood cells,
brown haemosidren
granules, heart failure cells
and homogenous pink
transudate. The heart failure
cells are large, rounded
phagocytic cells engulfing
brown haemosidren granules
and red blood cells.
Diagnosis
Chronic venous congestion,

Chronic venous congestion, lung

Chronic venous congestion liver
Atrophic
liver cells
Dilated
sinusoids
Central vein

EDEMAEDEMA
““Edema is the increased fluid in the interstitialEdema is the increased fluid in the interstitial
tissue spaces and or body cavities”tissue spaces and or body cavities”
Approximately 60% of lean body weight isApproximately 60% of lean body weight is
water, two thirds of which is intracellular, withwater, two thirds of which is intracellular, with
the reminder in the extra cellular compartments,the reminder in the extra cellular compartments,
mostly as interstitial fluid (only about 5% ofmostly as interstitial fluid (only about 5% of
total body water is in blood plasma). The termtotal body water is in blood plasma). The term
edema signifies increased fluid in the interstitialedema signifies increased fluid in the interstitial
tissue spaces.tissue spaces.

The interstitial tissue is in
equilibrium with plasma on one hand
and parenchymal cell cytoplasm on the
other.
 Movement of water and electrolytes
among plasma , interstitium, cells and
lymphatics is shown by arrows
Components of Interstitial tissue:
A. Water ; Electrolytes; Hydrogen ions; Glucose ; Lipids
B. Ground substance; Glycoprotein; Hyaluronic acid; Fibronectins
C. Fibrillar proteins ; Collagen( Osteoid in bone and chondroid in
cartilage); Elastin ;
D. Interstitial cells; Fibroblasts; Macrophages ; lymphocytes; Mast cells;
Adipocytes (fat cells)

NORMAL TISSUE FLUID CIRCULATIONNORMAL TISSUE FLUID CIRCULATION
Hydrostatic blood pressure forces water out of capillaries at the
arterial end, but the plasma oncotic pressure attributable to albumin
sucks water back into capillary beds at the venous end . A small
amount of water drains from the tissues through lymphatic channels

Variables Affecting Fluid Transit Across capillary Walls
Capillary hydrostatic and osmotic forces are normally balanced so that
there is no net loss or gain of fluid across the capillary bed. However
increased hydrostatic pressure or diminished plasma osmotic pressure
leads to a net accumulation of extravascular fluid(edema). As the
interstitial fluid pressure increases, tissue lypmhatics remove much of the
excess volume via thoracic duct. If the ability of the lypmhatics to drain fluid
is exceeded, persistent tissue edema results

PATHOPHYSIOLOGIC CATEGORIES OF EDEMAPATHOPHYSIOLOGIC CATEGORIES OF EDEMA
I.I. Increased Hydrostatic Pressure:Increased Hydrostatic Pressure:
a.a. Impaired venous returnImpaired venous return
Congestive heart failureCongestive heart failure
Constrictive pericarditisConstrictive pericarditis
Ascities (Liver Cirrhosis)Ascities (Liver Cirrhosis)
Venous obstruction or compression , e.g., ThrombosisVenous obstruction or compression , e.g., Thrombosis
b.b. Arteriolar dilatationArteriolar dilatation
HeatHeat
Neurohumoral dysregulationNeurohumoral dysregulation
II.II. Reduced Plasma Osmotic PressureReduced Plasma Osmotic Pressure
(Hypoprotenemia)(Hypoprotenemia)
Protein losing Glomerulonephritis (Nephrotic Syndrome)Protein losing Glomerulonephritis (Nephrotic Syndrome)
Liver Cirrhosis (Ascities)Liver Cirrhosis (Ascities)
MalnutritionMalnutrition
Protein – losing GastroenterophathyProtein – losing Gastroenterophathy

III.III. Lymphatic Obstruction:Lymphatic Obstruction:
InflammatoryInflammatory
NeoplasiaNeoplasia
Post surgicalPost surgical
Post irradiationPost irradiation
Parasitic ( Filaraisis)Parasitic ( Filaraisis)
IV.IV. InflammationInflammation ( increased capillary permeability)( increased capillary permeability)
Acute inflammationAcute inflammation
Chronic inflammationChronic inflammation
AngiogenesisAngiogenesis
V.V. Sodium RetentionSodium Retention
Excessive salt intake with renal insufficiencyExcessive salt intake with renal insufficiency
Increased tubular reabsorption of sodiumIncreased tubular reabsorption of sodium
Renal HypoperfusionRenal Hypoperfusion
Increased renin- angiotensin – aldosterone secretionIncreased renin- angiotensin – aldosterone secretion

Arterial EndArterial End Venous EndVenous End
Hydrostatic pressure is moreHydrostatic pressure is more
than osmotic pressurethan osmotic pressure
Osmotic pressure is moreOsmotic pressure is more
than hydrostatic pressurethan hydrostatic pressure

I.I. INCREASED HDROSTATIC PRESSUREINCREASED HDROSTATIC PRESSURE
Normal Hydrostatic pressure at the arteriolar end of capillaries is
mm of Hg and at the venular end of capillaries it is about 15 mm of Hg
eased venous pressure exceeds that of plasma oncotic pressure and
water remains in the tissues.
al increase in Hydrostatic Pressure: It result from impaired venous out flow.
example, deep venous thrombosis in the lower extremities leads to
ma which is restricted to lower limbs
eralized Increase in Venous Pressure: Generalized increase in venous
ssure, with resulting systemic edema, occur most commonly in con-
stive Heart Failure affecting left ventricle

Congestive heart failure is associated with reduced cardiac
output and therefore reduced renal perfusion. Renal
hypo perfusion, then triggers the Rennin- Angiotensin –
Aldosterone Axis, inducing sodium and water retention by
kidneys . This process is putatively designed to increase
intravascular volume and thereby improve cardiac out put
( via Frank- Starling Law) , with restoration of normal renal
perfusion . If the failing heart can not increase cardiac out put ,
however , the extra fluid load results only in increased venous
pressure and eventually Edema

Pathways leading to systemic edema due to primary heart failure, primary
renal failure, or reduced plasma oncotic pressure (e.g., from malnutrition,
diminished hepatic synthesis, or protein loss due to the nephrotic syndrome)

II.II.REDUCED PLASMA ONCOTIC PRESSUREREDUCED PLASMA ONCOTIC PRESSURE
(Hypoalbuminaemic oedema)(Hypoalbuminaemic oedema)
The normal colloid osmotic pressure is about 20 mm of Hg. It is an
pposing force to the hydrostatic pressure . Normally at arterial end
ltration of tissue fluids occur because the hydrostatic pressure is
igher than the osmotic pressure. At the venous end the osmotic
ressure is higher than the hydrostatic pressure resulting in the
ithdrawal of the tissue fluid. Therefore fall in the osmotic pressure
due to hypoprotenemia) results in oedema
ow plasma albumin concentration reduces the plasma oncotic
essure so that water can not be sucked back into the capillary bed
t the venous end.

Causes of hypoalbuminemia are:
(i) Protein malnutrition (as in Kwashiorkor)
(ii) Liver failure (reduced albumin synthesis)
(iii) Nephrotic syndrome (excessive albumin loss
in urine)
(iv) Protein – losing enteropathy (a variety of
diseases are responsible)
Hypoalbuminemia as the cause of oedema
can be verified easily by measuring the
albumin concentration in serum

III.III. LYMPHATIC OBSTRUCTIONLYMPHATIC OBSTRUCTION
(Lymphatic Oedema)(Lymphatic Oedema)
Lymphatic obstruction prevents drainage of water from tissues
Important causes of lymphatic obstruction are:
(i) Parasitic infection Filariasis often causes impairment in lymphatic
drainage and cause massive lymph edema in inguinal region
(Elephantiasis)
(ii) Surgical removal of axillary lymph nodes in carcinoma breast can
lead to lymph edema of arms.

Lymphatic ObstructionLymphatic Obstruction
 FilariasisFilariasis ––
 A parasitic infectionA parasitic infection
affecting inguinalaffecting inguinal
lymphatics resulting inlymphatics resulting in
elephantiasiselephantiasis

Lymphatic Obstruction NeoplasticLymphatic Obstruction Neoplastic
 Resection and/or radiation to axillary lymphaticsResection and/or radiation to axillary lymphatics inin
breast cancer patients can lead to --breast cancer patients can lead to -- arm edemaarm edema
 Carcinoma of breastCarcinoma of breast withwith obstructioobstruction of superficialn of superficial
lymphaticslymphatics can lead to edema of breast skin -- --withcan lead to edema of breast skin -- --with
an unusual appearance:an unusual appearance: “peau d’orange” (orange“peau d’orange” (orange
peel)peel)

IV.IV.INFLAMMATORY OEDEMAINFLAMMATORY OEDEMA
It is a feature of acute inflammation. In acutely inflamed tissues there is
increased vascular (mainly venular ) permeability due to separation of
endothelial cells under the influence of chemical mediators. Fluid with
high protein content leaks out of the permeable vessels into the inflam-
ed tissue causing it to swell.
There is increased lymphatic drainage, but this cannot cope with all the
water released into tissues and edema results

V.V.SODIUM AND WATER RETNETIONSODIUM AND WATER RETNETION
 Salt retention may occur with any acute reduction ofSalt retention may occur with any acute reduction of
renal functionrenal function
 Sodium and Water retention is clearly contributorySodium and Water retention is clearly contributory
factors in several forms of edemafactors in several forms of edema
 Increased salt, with obligate accompanying water ,Increased salt, with obligate accompanying water ,
causes bothcauses both
(i) increased hydrostatic pressure( due to expansion(i) increased hydrostatic pressure( due to expansion
of the intravascular fluid volume)of the intravascular fluid volume)
andand
(ii) Diminished vascular colloid osmotic pressure.(ii) Diminished vascular colloid osmotic pressure.

Pathophysiology of Localized EdemaPathophysiology of Localized Edema
Factors influencing accumulation in the interstitial spaceFactors influencing accumulation in the interstitial space
PathologicPathologic
conditioncondition
VascularVascular
permeabilitypermeability
CapillaryCapillary
HydrostaticHydrostatic
PressurePressure
InterstitialInterstitial
TissueTissue
OsmoticOsmotic
PressurePressure
LymphaticLymphatic
FlowFlow
AcuteAcute
InflammatoryInflammatory
EdemaEdema
IncreasedIncreased IncreasedIncreased Normal OrNormal Or
IncreasedIncreased
IncreasedIncreased
AllergicAllergic
EdemaEdema
IncreasedIncreased IncreasedIncreased Normal OrNormal Or
IncreasedIncreased
IncreasedIncreased
Edema ofEdema of
VenousVenous
ObstructionObstruction
NormalNormal IncreasedIncreased NormalNormal IncreasedIncreased
Edema ofEdema of
LymphaticLymphatic
ObstructionObstruction
NormalNormal NormalNormal Normal OrNormal Or
IncreasedIncreased
DecreasedDecreased

MORPHOLOGY OF OEDEMAMORPHOLOGY OF OEDEMA
Gross FeaturesGross Features :: Oedema causes swelling, heaviness andOedema causes swelling, heaviness and
pallor of the affected tissue . The cut surface of anpallor of the affected tissue . The cut surface of an
oedematous organ, as lung, oozes fluidoedematous organ, as lung, oozes fluid
Microscopic Features:Microscopic Features: Oedema appears asOedema appears as homogenoushomogenous
pale eosinophilic substancepale eosinophilic substance . Eosinophilic staining is. Eosinophilic staining is
due to its protein content . Pale staining is due to fluiddue to its protein content . Pale staining is due to fluid
dilution.dilution.
Microscopically oedema fluid generally manifests as cellMicroscopically oedema fluid generally manifests as cell
swelling with clearing and separation of extra cellularswelling with clearing and separation of extra cellular
matrix elements.matrix elements.

TYPES OF OEDEMATYPES OF OEDEMA
I.I. Localized Or GeneralizedLocalized Or Generalized
II.II. Pitting Or Non- pittingPitting Or Non- pitting
III.III. Transudate Or ExudateTransudate Or Exudate

I.I. Localized Or GeneralizedLocalized Or Generalized
Localized:Localized:
a. Inflammatory Oedemaa. Inflammatory Oedema
b. Lymphatic oedema due to lymphatic obstructionb. Lymphatic oedema due to lymphatic obstruction
c. Oedema due to localized venous congestionc. Oedema due to localized venous congestion
d. Pulmonary oedemad. Pulmonary oedema
Generalized:Generalized:
a. Cardiac Oedema: Seen in right sided heart failure.a. Cardiac Oedema: Seen in right sided heart failure.
b. Nutritional Oedema: Due to hypoprotenemia seen in:b. Nutritional Oedema: Due to hypoprotenemia seen in:
- Malnutrition- Malnutrition
- Malabsorption- Malabsorption
- Chronic liver disease ( decreased protein synthesis)- Chronic liver disease ( decreased protein synthesis)
c. Renal Oedema: It particularly starts around the eye lidsc. Renal Oedema: It particularly starts around the eye lids
then becomes generalized.then becomes generalized.

II.II.Pitting Or Non- Pitting OedemaPitting Or Non- Pitting Oedema
Pitting Oedema:Pitting Oedema: Pitting oedema occurs when venousPitting oedema occurs when venous
pressurepressure
is increased ( e.g., right sided heart failure) or osmoticis increased ( e.g., right sided heart failure) or osmotic
pressurepressure
is decreased ( e.g., hypoprotenemia)is decreased ( e.g., hypoprotenemia)
It is more marked in theIt is more marked in the dependent partsdependent parts ( feet in an( feet in an
ambulantambulant
patient and the sacrum in a bed ridden patient)patient and the sacrum in a bed ridden patient)
If the edematous part is pressed by the thumb , aIf the edematous part is pressed by the thumb , a pitpit isis
formed which refills slowly after the thumb is removed.formed which refills slowly after the thumb is removed.
Dorsum of theDorsum of the
foot ,ankle, shin and sacrum are the usual sites to look forfoot ,ankle, shin and sacrum are the usual sites to look for
pittingpitting
edema.edema.
Non – Pitting Oedema:Non – Pitting Oedema: When thumb is pressed no pittingWhen thumb is pressed no pitting
takes place.takes place.
Non- pitting oedema takes place in different sites.Non- pitting oedema takes place in different sites.
1. In cases of lymphatic oedema, e.g., Filaraisis.1. In cases of lymphatic oedema, e.g., Filaraisis.

IIIIII.. TRANSUDATE Or EXUDATETRANSUDATE Or EXUDATE
The edema fluid occurring in hydrodynamicThe edema fluid occurring in hydrodynamic
derangements is typicallyderangements is typically protein – poorprotein – poor
Transudate,Transudate, .. Conversely, because of increasedConversely, because of increased
vascular permeability , inflammatory edema isvascular permeability , inflammatory edema is
protein rich - Exudate.protein rich - Exudate.

TRANSUDATE EXUDATE
PROTEIN Less than 3.o g/dl More than 3.0 gram/dl
COLOUR : .Clear Or Straw Turbid or Purulent
SPECIFIC GRAVITY Less than 1.012 More than 1.012
CELL COUNT Less than 100/cmm More than 100/cmm
TYPE OF CELL: Lymphocytes &
mesothelial
Lmphocytes &
Neutrophils
RED BLOOD CELLS: Absent Often present
CLOT FORMATION None Usual
TOTAL PROTEIN: Less than 3.0 g/dl More than 3.0 g/dl
RIVOLTA TEST Negative Positive
GLUCOSE As in plasma Reduced
LDH Less than 550 Units More than 550 units
Transudate VS ExudateTransudate VS Exudate

TRANSUDATE EXUDATE
CAUSES (i) Congestive
Cardiac Failure
(ii) Cirrhosis
(i) Bacterial Infection
(ii) Malignancies
(iii) Tuberculosis
PROTEIN SOURCE Mainly Albumin Mainly Fibrinogen
NATURE Normal tissue fluid but
in amounts exceeding
the normal
Inflammatory Fluid
Transudate VS ExudateTransudate VS Exudate

CLINICAL CORRELATIONSCLINICAL CORRELATIONS
HYDROTHORAX:HYDROTHORAX: Accumulation of fluid in pleural cavityAccumulation of fluid in pleural cavity
HYDROPERICARDIUM:HYDROPERICARDIUM: Accumulation of fluid inAccumulation of fluid in
pericardiumpericardium
ASCITIES:ASCITIES: Accumulation of fluid in peritoneal cavityAccumulation of fluid in peritoneal cavity
ANASARCA:ANASARCA: Severe and generalized edema withSevere and generalized edema with
profound subcutaneous tissue swellingprofound subcutaneous tissue swelling

Edema -Edema - MorphologyMorphology
 Dependent EdemaDependent Edema is a prominentis a prominent
feature of Congestive Heartfeature of Congestive Heart
FailureFailure
 Facial EdemaFacial Edema is often the initialis often the initial
manifestation of Nephrotic Syndromemanifestation of Nephrotic Syndrome
Subcutaneous EdemaSubcutaneous Edema
 Edema of the subcutaneous tissue is most easily detectedEdema of the subcutaneous tissue is most easily detected GrosslyGrossly (not(not
microscopically)microscopically)
 Push your finger into itPush your finger into it
 and a depression remainsand a depression remains

Non –pitting EdemaNon –pitting Edema

Periorbital edema in Nephrotic SyndromePeriorbital edema in Nephrotic Syndrome

EdemaEdema
Clinical Correlation:Clinical Correlation:
Subcutaneous EdemaSubcutaneous Edema
 Annoying but Points to Underlying DiseaseAnnoying but Points to Underlying Disease
 However, it can impair wound healing orHowever, it can impair wound healing or
clearance of Infectionclearance of Infection

Edema-Edema- MorphologyMorphology
Pulmonary EdemaPulmonary Edema
is most frequently seen in Congestive Heartis most frequently seen in Congestive Heart
FailureFailure
 May also be present in renal failure, adultMay also be present in renal failure, adult
respiratory distress syndrome (ARDS),respiratory distress syndrome (ARDS),
pulmonary infections and hypersensitivitypulmonary infections and hypersensitivity

Pulmonary Edema-Gross:Pulmonary Edema-Gross:
 The Lungs are typically 2-3 times the normal weightThe Lungs are typically 2-3 times the normal weight
 Cross sectioning causes an outpouring of frothy,Cross sectioning causes an outpouring of frothy,
sometimes blood-tinged fluidsometimes blood-tinged fluid

EDEMA -EDEMA - SummarySummary
INCREASED
HYDROSTATIC
PRESSURE
Congestive Heart Failure
Ascites
Venous Obstruction
DECREASED
ONCOTIC
PRESSURE
Nephrotic Syndrome
Cirrhosis
Protein Malnutrition
INCREASED
PERMEABILITY
Inflammation
LYMPHATIC
OBSTRUCTION
Inflammatory
Neoplastic
 HEARTHEART
 LIVERLIVER
 KIDNEYKIDNEY

GENERALIZED EDEMAGENERALIZED EDEMA
 HEARTHEART
 LIVERLIVER
 KIDNEYKIDNEY

HAEMORRHAGEHAEMORRHAGE
 ““Extravasations of blood from vessels”Extravasations of blood from vessels”
 Occurs in variety of settingsOccurs in variety of settings
 Risk of haemorrhage (often after a seemingly insignificantRisk of haemorrhage (often after a seemingly insignificant
injury) is increased in a wide variety of clinical disordersinjury) is increased in a wide variety of clinical disorders
collectively calledcollectively called Haemorrhagic DiathesisHaemorrhagic Diathesis
 Trauma, atherosclerosis, or inflammatory or neoplasticTrauma, atherosclerosis, or inflammatory or neoplastic
erosion of a vessel wall also may lead to haemorrhage,erosion of a vessel wall also may lead to haemorrhage,
which may be extensivewhich may be extensive

HAEMORRHAGE …. ManifestationsHAEMORRHAGE …. Manifestations
Haemorrhage may be manifested by different appearances andHaemorrhage may be manifested by different appearances and
clinical consequencesclinical consequences
1.1. Haematoma :Haematoma : Haemorrhage may be external or accumulateHaemorrhage may be external or accumulate
within a tissue as a Haematoma ; which ranges inwithin a tissue as a Haematoma ; which ranges in
significance from trivial (e.g., asignificance from trivial (e.g., a bruisebruise) to fatal 9e.g.,) to fatal 9e.g.,
Massive Rretroperitoneal Haematoma resulting fromMassive Rretroperitoneal Haematoma resulting from
RRupture of a Dissecitng Aortic Aneurysmupture of a Dissecitng Aortic Aneurysm ))
2.2. HemothoraxHemothorax
33. Hemoperitonium. Hemoperitonium
4.4.HemopericardiumHemopericardium
5.5. HemarthrosisHemarthrosis
6.6. Petichiae:Petichiae: Minute (1 to 2 mm in diameter) hemorrhage intoMinute (1 to 2 mm in diameter) hemorrhage into
skin, mucous membranes or serosal surfaces.skin, mucous membranes or serosal surfaces.
Causes include:Causes include:
(i)(i) ThrombocytopniaThrombocytopnia
(ii)(ii) Platelet function defectsPlatelet function defects
(iii)(iii) Loss of vascular wall support (Vitamin C deficiency)Loss of vascular wall support (Vitamin C deficiency)

7.7. PurpuraPurpura:: Slightly larger (3 to 5 mm) haemorrhages. CanSlightly larger (3 to 5 mm) haemorrhages. Can
result form the same disorders that cause petechiae, as wellresult form the same disorders that cause petechiae, as well
as trauma ,vascular inflammation (vasculitis and increasedas trauma ,vascular inflammation (vasculitis and increased
vascular fragilityvascular fragility
8.8. EcchmosesEcchmoses :: Are larger (1 to 2 cm) subcutaneousAre larger (1 to 2 cm) subcutaneous
hamatomas (colloquially calledhamatomas (colloquially called BruisesBruises ))

 Clinical significance of any particular haemorrhage dependsClinical significance of any particular haemorrhage depends
on the volume of blood lost and the rate of bleedingon the volume of blood lost and the rate of bleeding
 Greater loss can lead toGreater loss can lead to Hypovolemic ShockHypovolemic Shock
 Site of haemorrhage is also importantSite of haemorrhage is also important
 Chronic or recurrent external blood loss (e.g., due to pepticChronic or recurrent external blood loss (e.g., due to peptic
ulcer or menstrual bleeding) frequently culminates in ironulcer or menstrual bleeding) frequently culminates in iron
deficiency as a consequence of loss of iron indeficiency as a consequence of loss of iron in
haemoglobinhaemoglobin

THROMBOSISTHROMBOSIS
 The formation of a clotted mass of bloodThe formation of a clotted mass of blood
within the non interrupted cardiovascularwithin the non interrupted cardiovascular
system is termed thrombosis,system is termed thrombosis, and the mass itselfand the mass itself
ThrombusThrombus
 Thrombosis is the formation of a solid mass from theThrombosis is the formation of a solid mass from the
constituents of blood (platelets, fibrin and entrapped redconstituents of blood (platelets, fibrin and entrapped red
and white cells) within the heart or vascular system in aand white cells) within the heart or vascular system in a
living organismliving organism

Normal HemstasisNormal Hemstasis is the result of a set of well regulatedis the result of a set of well regulated
processes that accomplish two important functions:processes that accomplish two important functions:
(i) It maintain(i) It maintain blood in a fluid, clot free stateblood in a fluid, clot free state in normalin normal
vessels.vessels.
(ii) It produces a localized(ii) It produces a localized Haemostatic PlugHaemostatic Plug at the siteat the site
of vascular injury.of vascular injury.
The pathologic opposite to hemostasis isThe pathologic opposite to hemostasis is ThrombosisThrombosis
Both Hemostasis and Thrombosis depend on threeBoth Hemostasis and Thrombosis depend on three
components:components:
(i) The Vascular Wall(i) The Vascular Wall
(ii) Platelets(ii) Platelets
(iii) Coagulation Cascade(iii) Coagulation Cascade

INVOLVEMENT OF BLOOD VESSELS, PLATELETSINVOLVEMENT OF BLOOD VESSELS, PLATELETS
AND BLOOD COAGULATION IN HAEMOSTASISAND BLOOD COAGULATION IN HAEMOSTASIS

Mechanism of normal Haemostasis
A: In normal uninjured blood vessels sub endothelial
connective tissue, especially collagen and elastin, is not
exposed to the circulating blood.
B: In the first few seconds after injury, exposure of
sub endothelial tissue attracts platelets, which adhere
at the site of injury. Endothelial injury also activates
Hageman factor (factor XII) , which in turn activates the
intrinsic pathway of coagulation cascade. Release of tissue
thromboplastin activates the extrinsic pathway.
C: Haemostasis is achieved in minutes. Platelet
degranulation stimulates further platelet aggregation .
Fibrin formed by activation of the coagulation cascade
combines with the mass of aggregated platelets to form
the definitive haemostatic plug that seals the injury .
Plasmin (fibrinolysin) formed by the activation of
fibrinolytic pathway prevents excessive fibrin formation.
D: During healing (hours to days), the thrombus retracts , and
organization and fibrosis of the thrombus occurs.
Reendotheliazation of the vessels is the final step

Primary Haemostasis: Endothelial injury
exposes highly thrombogenic sub-endothelial
extracellular matrix , facilitating platelet adherence
,activation and aggregation .The formation of the initial
platelet plug is called primary haemostasis
Secondary Haemostasis: Activated thrombin
promotes the formation of an insoluble fibrin clot by
cleaving fibrinogen ; thrombin also is a potent activator
of additional platelets, which serve to reinforce the
haemostatic plug . This sequence termed secondary
haemostasis , results in the formation of a stable clot
capable of preventing further haemorrhage
Primary And Secondary haemostaticPrimary And Secondary haemostatic
HaemostasisHaemostasis

ROLE OF ENDOTHELIUM IN HAEMOSTASISROLE OF ENDOTHELIUM IN HAEMOSTASIS
Intact endothelium cells serve primarily to inhibit platelet adherence and blood
clotting. While injury or activation of endothelial cell result in procoagulant effect
that augments local clot formation
Anti platelet substances in Endothelium: (i) Prostacyclin (ii) Nitric Oxide
(iii) Adenosine diphosphate
Anticoagulant substances in Endothelium: (i) Antithrombin III (ii) Thrombomodulin
(iii) Protein C (iv) Protein S

Endothelial cells and Coagulation- Summary
Intact normal endothelial cell help to maintain blood
flow by inhibiting the activation of platelets and
coagulation factors
Endothelial cells stimulated by injury or inflammatory
cytokines up-regulate expression of pro-cogulant factors
(e.g., tissue factor) that promotes clotting and down
regulate expression of anticoagulant factors
Loss of endothelial integrity exposes sub-endothelial
vWF and basement membrane collagen, stimulating
platelet adhesion , platelet activation and clot formation

ROLE OF PLATELETS IN HAEMOSTASISROLE OF PLATELETS IN HAEMOSTASIS
Platelets Adhesion and Aggregation: Von Willebrand’s Factor
functions as a bridge between sub endothelial collagen and the
Gp Ib platelet receptor. Aggregation involves linking platelets
via fibrinogen bridges bound to the platelet GpIIb- IIIa receptors

Platelets Adhesion
Platelet Activation
Shape Change
Release Reaction
Platelet Aggregation

n

(I)Platelets Adhesion Defects:
-Von Willebrand Disease:Congenital Deficiency/Absence
of von Willebrand Factor leads to inherited bleeding
disorder- von Willebrand Disease
-Beranrd Soulier Disease: Absence of Gp1b- Leads to
inherited bleeding disorder Bernard Soulier
Disease
(II) Platelets Aggregation Defects: Absence of
GpIIb/IIIa- leads to inherited bleeding disorder-
Glanzmann thormobasthenia

Platelet Adhesion, Activation and Aggregation- Summary
Endothelial injury exposes the underlying basement membrane ECM;
platelets adhere to the ECM primarily through binding of platelet GpIb
receptor to vWF
Adhesion leads to platelet activation , an event associated with
secretion of platelet granule contents, including calcium ( a cofactor for
several coagulation proteins) and ADP ( a mediator of further platelet
activation) ; dramatic changes in shape and membrane composition;
and activation of GpIIb/IIIa receptors
The GpIIb/IIIa receptors on activated platelets form bridging cross links
with fibrinogen ,leading to platelet aggregation
Concomitant activation of thrombin promotes fibrin deposition,
cementing the platelet plug in place

ROLE OF COAGULATION SYSTEM IN HAEMOSTASISROLE OF COAGULATION SYSTEM IN HAEMOSTASIS
INTRINSIC PATHWAY EXTRINSIC PATHWAY
kalikrein Kallikrein VII VIIa
XIII XIIa
HMWK
XI XIa
IX IXa
Ca++
X Xa
VIIICa++
; Pl
Prothrombin (II) Thrombin ( IIa )
Ca++
; Pl
Fibrinogen(I) Fibrin (Ia)
XIII XIIIa
COMMON
PATHWAY
Tissue Factor
Ca++
; Pl

CAOGULATION SYSTEMCAOGULATION SYSTEM
Coagulation System comprises of several proteinsCoagulation System comprises of several proteins
which are normally present in the blood in an inactive form.which are normally present in the blood in an inactive form.
When there is injury to the blood vessels, the coagulationWhen there is injury to the blood vessels, the coagulation
system becomes activated and results in the formation of asystem becomes activated and results in the formation of a
fibrin clot. Fibrin enmeshes the platelet aggregate at thefibrin clot. Fibrin enmeshes the platelet aggregate at the
site of vascular injury and converts the instable primarysite of vascular injury and converts the instable primary
platelet plug to firm , definitive and stable haemostaticplatelet plug to firm , definitive and stable haemostatic
plug.plug.
In the coagulation cascade first there is initiation ofIn the coagulation cascade first there is initiation of
Intrinsic and Extrinsic Pathways. Both of these thenIntrinsic and Extrinsic Pathways. Both of these then
converge onto the activation of Common Pathway. Theconverge onto the activation of Common Pathway. The
Common Pathway then at the end leads to the formation ofCommon Pathway then at the end leads to the formation of
a stable haemostatic pluga stable haemostatic plug
EXTRINSIC PATHWAY:EXTRINSIC PATHWAY:
In the Extrinsic pathway, the factors released fromIn the Extrinsic pathway, the factors released from
damaged tissues activate factor VII which in turn in thedamaged tissues activate factor VII which in turn in the
presence of Tissue Factor, activates factor X.presence of Tissue Factor, activates factor X.

INTRNISIC PATHWAY:INTRNISIC PATHWAY:
In this pathway initially factor XII is activated, when itIn this pathway initially factor XII is activated, when it
comes in contact with sub endothelial elements of the bloodcomes in contact with sub endothelial elements of the blood
vessels including collagen, High Molecular Weigh Kininogenvessels including collagen, High Molecular Weigh Kininogen
(HMWK) and Kalikrein . The activated factor XIIa then(HMWK) and Kalikrein . The activated factor XIIa then
converts factor XI into its activated form XIa. The next stepconverts factor XI into its activated form XIa. The next step
is the conversion of IX into IXa by factor XIa. Factor IXa inis the conversion of IX into IXa by factor XIa. Factor IXa in
the presence of calcium, platelets and factor VIII thenthe presence of calcium, platelets and factor VIII then
converts X to Xa.converts X to Xa.
COMMON PATHWAY:COMMON PATHWAY:
The common pathway is initiated by the conversion of factorThe common pathway is initiated by the conversion of factor
X in into Xa. Activated Factor X (Xa) then convertsX in into Xa. Activated Factor X (Xa) then converts
Prothrombin (II) into Thrombin (IIa), and for this Factor V,Prothrombin (II) into Thrombin (IIa), and for this Factor V,
Calcium ions and Platelets are required. Thrombin thenCalcium ions and Platelets are required. Thrombin then
converts fibrinogen (I) into fibrin monomers (IIa). The fibrinconverts fibrinogen (I) into fibrin monomers (IIa). The fibrin
monomers form cross linking meshwork under the influencemonomers form cross linking meshwork under the influence
of activated factor XIII . In this meshwork blood cells getof activated factor XIII . In this meshwork blood cells get
entangled to form a clot.entangled to form a clot.

SEQUENCE OF HAEMOSTATIC EVENTS ATSEQUENCE OF HAEMOSTATIC EVENTS AT
THE SITE OF VASCULAR INJURYTHE SITE OF VASCULAR INJURY
The general sequence of events in haemostasis atThe general sequence of events in haemostasis at
the site of vascular injury are:the site of vascular injury are:
First Phase : Blood Vessel Wall Response:First Phase : Blood Vessel Wall Response: After injury,After injury,
there is a brief period of arteriolarthere is a brief period of arteriolar VasoconstrictionVasoconstriction ,,
largely attributable to reflex neurogenic mechanismslargely attributable to reflex neurogenic mechanisms
and augmented by the local secretion of factors such asand augmented by the local secretion of factors such as
endothelium derived vasoconstrictors. The effect isendothelium derived vasoconstrictors. The effect is
transient and bleeding will resume if platelets andtransient and bleeding will resume if platelets and
coagulation system are not activated.coagulation system are not activated.
Second Phase: Platelets Adhesion, Activation, ShapeSecond Phase: Platelets Adhesion, Activation, Shape
change, Release Reaction and Aggregation:change, Release Reaction and Aggregation: EndothelialEndothelial
injury exposes highly thrombogenic subendothelialinjury exposes highly thrombogenic subendothelial
matrix, which allows platelets to adhere and becomematrix, which allows platelets to adhere and become
activated that is, to undergo a shape change and releaseactivated that is, to undergo a shape change and release
secretary granules. Within minutes the secretedsecretary granules. Within minutes the secreted
products have recruited additional platelets to form aproducts have recruited additional platelets to form a
haemostatic plughaemostatic plug ((Primary Haemostatic Plug)Primary Haemostatic Plug)

Third Phase: Activation of Intrinsic and Extrinsic PathwaysThird Phase: Activation of Intrinsic and Extrinsic Pathways
of Coagulation:of Coagulation:
Tissue FactorTissue Factor a membrane bound procagulant factor,a membrane bound procagulant factor,
synthesized by endothelium, is also exposed at the sitesynthesized by endothelium, is also exposed at the site
of injury. It acts in conjunction with the secreted plateletof injury. It acts in conjunction with the secreted platelet
factors to activate the coagulation cascade, culminatingfactors to activate the coagulation cascade, culminating
in the activation ofin the activation of ThrombinThrombin . In turn, thrombin converts. In turn, thrombin converts
circulating soluble fibrinogen to insoluble fibrin resultingcirculating soluble fibrinogen to insoluble fibrin resulting
in local fibrin deposition. Thrombin also induces furtherin local fibrin deposition. Thrombin also induces further
platelet recruitment and granule release. Whole thisplatelet recruitment and granule release. Whole this
sequence is calledsequence is called Secondary Haemostasis.Secondary Haemostasis.
Polymerized fibrin and platelets aggregates form aPolymerized fibrin and platelets aggregates form a
solid,solid, permanent plugpermanent plug to prevent any furtherto prevent any further
haemorrhage.haemorrhage.
Dissolution of ClotDissolution of Clot :: Once the clot is formed counterOnce the clot is formed counter
regulatory mechanisms, likeregulatory mechanisms, like Fibrinolytic SystemFibrinolytic System are setare set
into action to restrict the haemostatic plug to the site ofinto action to restrict the haemostatic plug to the site of
injuryinjury

The involvement of blood vessels, platelets and blood coagulation in
hemostasis

Screening TestsScreening Tests
ForFor
BloodBlood
CoagulationCoagulation

Screening Tests of BloodScreening Tests of Blood
CoagulationCoagulation
Screening tests provide an assessment of the ‘extrinsic’ and ‘intrinsic’Screening tests provide an assessment of the ‘extrinsic’ and ‘intrinsic’
systems of blood coagulation and also the central conversion ofsystems of blood coagulation and also the central conversion of
fibrinogen into fibrinfibrinogen into fibrin..
Prothrombin Time (PT) :Prothrombin Time (PT) :Measures factors VII, X, V, prothrombin andMeasures factors VII, X, V, prothrombin and
fibrinogen. Tissue thrombopolastin (a brain extract) and calcium arefibrinogen. Tissue thrombopolastin (a brain extract) and calcium are
added to citrated plasma. The normal time for clotting is 10-14 seconds.added to citrated plasma. The normal time for clotting is 10-14 seconds.
(measures extrinsic & common pathway).(measures extrinsic & common pathway).
Activated Partial Thromboplastin Time (APTT):Activated Partial Thromboplastin Time (APTT):Measures factorsMeasures factors
VIII, IX, XI and XII in addition to factor, X, V, prothrombin andVIII, IX, XI and XII in addition to factor, X, V, prothrombin and
fibrinogen. Three substances, phospholipids, a surface activator (e.g.fibrinogen. Three substances, phospholipids, a surface activator (e.g.
kaolin) and calcium- are added to citrated plasma. The normal time forkaolin) and calcium- are added to citrated plasma. The normal time for
clotting is about 30-40 seconds. (Measures intrinsic & commonclotting is about 30-40 seconds. (Measures intrinsic & common
pathway).pathway).
Thrombin Time (TT):Thrombin Time (TT): is sensitive to a deficiency of fibrinogen.is sensitive to a deficiency of fibrinogen.
Diluted bovine thrombin is added to citrated plasma at a concentrationDiluted bovine thrombin is added to citrated plasma at a concentration
giving a clotting time of 14-16 seconds with normal subjectgiving a clotting time of 14-16 seconds with normal subject..

Screening Tests of Blood Coagulation-InterpretationScreening Tests of Blood Coagulation-Interpretation
Prothrombin Time: (PT)Prothrombin Time: (PT)
Abnormalities indicated by prolongation: Deficiency or inhibition of oneAbnormalities indicated by prolongation: Deficiency or inhibition of one
or more of the following coagulation factors: VII, X, V, IV, fibrinogen.or more of the following coagulation factors: VII, X, V, IV, fibrinogen.
Most common cause of prolonged PT:Most common cause of prolonged PT:
1.1. Liver diseaseLiver disease 3.3. D.I.CD.I.C
2.2. Warfarin therapyWarfarin therapy 4.4. Heparin therapyHeparin therapy

Activated Partial Thromboplastin Time (APTT)Activated Partial Thromboplastin Time (APTT)
Abnormalities indicated by prolongation: Deficiency or inhibition of oneAbnormalities indicated by prolongation: Deficiency or inhibition of one
oror
more of the following coagulation factors: XII, XI, IX (Christmas diseasemore of the following coagulation factors: XII, XI, IX (Christmas disease
oror
Haemophilia B) VIII (haemphilia A) X, V, II, fibrinogen.Haemophilia B) VIII (haemphilia A) X, V, II, fibrinogen.
Most common causes of prolonged APTT:Most common causes of prolonged APTT:
1.1. HemophiliaHemophilia 3.3. D.I.C.D.I.C.
2.2. Christmas diseaseChristmas disease 4.4. Heparin therapyHeparin therapy
III)Thrombin Time (TT)III)Thrombin Time (TT)
Abnormalities indicated by prolongation: Deficiency or abnormality ofAbnormalities indicated by prolongation: Deficiency or abnormality of

Anticoagulant Therapy- MonitoringAnticoagulant Therapy- Monitoring
Oral Anticoagulant Parental Anticoagulant
-Prothrombin Time (PT)
-INR
-Activated Partial
Thromboplastin TIME
(APTT)

Anti-clotting MechanismsAnti-clotting Mechanisms
One of the major functions of homeostasis is to keep the blood in fluidOne of the major functions of homeostasis is to keep the blood in fluid
state. When a clot forms repair mechanisms start which close the gap instate. When a clot forms repair mechanisms start which close the gap in
the blood vessel permanently and at the same time the clot which isthe blood vessel permanently and at the same time the clot which is
formed is gradually broken down so that the circulation may be re-formed is gradually broken down so that the circulation may be re-
established. Besides this, clotting should also be limited to the requiredestablished. Besides this, clotting should also be limited to the required
site. This is achieved by anticlotting mechanisms.site. This is achieved by anticlotting mechanisms.
The substances which normally keep the blood in the fluid state are:The substances which normally keep the blood in the fluid state are:
  (i)(i)Anti thrombin IIIAnti thrombin III
  (ii)(ii) Protein CProtein C
  (iii)(iii) Protein SProtein S
(iv)(iv) Tissue factor Pathway InhibitorTissue factor Pathway Inhibitor

Once the clot is formed then its lysis takes places byOnce the clot is formed then its lysis takes places by fibrinolyticfibrinolytic
systemsystem..

Coagulation Factors- Summary
-Coagulation occurs via sequential enzymatic conversion of a cascade of
circulating and locally synthesized proteins
-Tissue factor elaborated at sites of injury is the most important initiator of
the coagulation cascade in vivo
-At the final stage of coagulation , thrombin converts fibrinogen into
insoluble fibrin that contributes to formation of the definitive haemostatic
plug
-Coagulation normally is restricted to sites of vascular injury by:
- Limiting enzymatic activation to phospholipid surfaces provided by
activate platelets or endothelium
- natural anticoagulants elaborated at sites of endothelial injury or during
activation of coagulation cascade
- Expression of thrombomodulin on normal endothelial cells, which binds
thrombin and converts it into and anticoagulant
- Activation of fibrinolytic system ( e.g., by association of tissue
palsminogen activator with fibrin_

The formation of a clotted mass of blood within the nonThe formation of a clotted mass of blood within the non
interrupted cardiovascular system is termed thrombosis,interrupted cardiovascular system is termed thrombosis,
and the mass itself Thrombusand the mass itself Thrombus
Thrombosis is the formation of a solid mass from theThrombosis is the formation of a solid mass from the
constituents of blood (platelets, fibrin and entrapped red and whiteconstituents of blood (platelets, fibrin and entrapped red and white
cells) within the heart or vascular system in a living organism.cells) within the heart or vascular system in a living organism.
Thrombosis Vs Blood ClotThrombosis Vs Blood Clot:: TheThe thrombosis is usuallythrombosis is usually
distinguished fromdistinguished from Blood ClotBlood Clot although the distinction isalthough the distinction is
somewhat arbitrary and both invoke the coagulation cascade.somewhat arbitrary and both invoke the coagulation cascade.
Clotting occurs in tissues when blood escapes from an injuredClotting occurs in tissues when blood escapes from an injured
vessel (hematoma formation) . It also occurs in vessels after deathvessel (hematoma formation) . It also occurs in vessels after death
(postmortem clotting of blood) and in vitro ( in a test tube outside(postmortem clotting of blood) and in vitro ( in a test tube outside
the body) . A thrombus is generally attached to the endothelium andthe body) . A thrombus is generally attached to the endothelium and
is composed of layers of aggregated platelets and fibrin ,is composed of layers of aggregated platelets and fibrin ,
whereas a blood clot contains randomly oriented fibrin withwhereas a blood clot contains randomly oriented fibrin with
entrapped platelets and red cellsentrapped platelets and red cells
Clearly the development of a blood clot is life saving when aClearly the development of a blood clot is life saving when a
large vessel ruptures or severed. However, when a thrombuslarge vessel ruptures or severed. However, when a thrombus
develops in the unruptured cardiovascular system, it may be lifedevelops in the unruptured cardiovascular system, it may be life
threateningthreatening

SUMMARY OF THROMBOGENESISSUMMARY OF THROMBOGENESIS
1.Endothelial injury releases tissue factor and
exposes sub endothelial connective tissues
2. Platelet adherence and plasma clotting system
are triggered.
3. Granule release and prostaglandin generation
begins
4. Platelet aggregation induced by released ADP
and vasoconstriction (5HT, Thromboxane) result
in primary (temporary) haemostatic plug.
5. Thrombin, thromboxanes, and endoperoxiedes
promote releases reaction and irreversible
aggregation. Platelet mass and trapped red cells
are
enmeshed in fibrin to form definitive
(permanent)
haemostatic plug.
6. Endothelial plasmnogen activator and plasma
antithrombin check rapid clotting

PATHOGENESIS OF THROMBOSISPATHOGENESIS OF THROMBOSIS
Three primary influences predispose to thrombus formation, theThree primary influences predispose to thrombus formation, the
so calledso called Virchow’s Triad:Virchow’s Triad:
(i) Endothelial Injury(i) Endothelial Injury
(ii) Stasis or turbulence of blood flow(ii) Stasis or turbulence of blood flow
(iii) Blood Hypercoagubality(iii) Blood Hypercoagubality
Virchow’s Triad in Thrombosis:
Endothelial injury is the single most
important factor. Note that injury to
endothelial cells can affect local blood
flow and/or coagulability.
Abnormal blood flow (stasis or
turbulence) in turn, cause endothelial
injury.The factors may act
independently or may combine to
cause thrombus formation

I.I.ENDOTHELIAL INJURYENDOTHELIAL INJURY
Endothelial damage stimulates both plateletEndothelial damage stimulates both platelet
adhesion and activation of the coagulation cascade.adhesion and activation of the coagulation cascade.
Endothelial injury is frequently an initiating factor whenEndothelial injury is frequently an initiating factor when
thrombus occurs in the arterial circulation. Whenthrombus occurs in the arterial circulation. When
thrombosis occurs in veins and in microcirculation thenthrombosis occurs in veins and in microcirculation then
endothelial injury is less conspicuous.endothelial injury is less conspicuous.
Common causes of endothelial injury are:Common causes of endothelial injury are:
(i) In heart and arterial circulation the endothelial injury(i) In heart and arterial circulation the endothelial injury
is seen in myocardial infarction and valvulitis.is seen in myocardial infarction and valvulitis.
(ii) Toxins from inflammatory processes(ii) Toxins from inflammatory processes
(iii) local compression of vessels (e.g., during operation)(iii) local compression of vessels (e.g., during operation)

II.II.ALTERATIONS IN BLOOD FLOWALTERATIONS IN BLOOD FLOW
The two factors which contributes to formation of thrombosisThe two factors which contributes to formation of thrombosis
by altering the normal blood flow are:by altering the normal blood flow are:
(i)(i) Turbulence in Blood Flow:Turbulence in Blood Flow: Turbulence means deviation ofTurbulence means deviation of
the blood stream which become distorted and abnormally hitsthe blood stream which become distorted and abnormally hits
the vascular and cardiac lining ; thus not only deviating thethe vascular and cardiac lining ; thus not only deviating the
platelets towards the endothelium, but also lead to endothelialplatelets towards the endothelium, but also lead to endothelial
damage. It contributes todamage. It contributes to arterial and cardiac thrombosisarterial and cardiac thrombosis
(ii)(ii) Stasis in Blood Flow:Stasis in Blood Flow: It is the major factor in theIt is the major factor in the
development ofdevelopment of venous thrombosisvenous thrombosis
The normal blood flow isThe normal blood flow is LAMINARLAMINAR. In laminar blood flow. In laminar blood flow
the cellular elements flow centrally in the vessel lumen,the cellular elements flow centrally in the vessel lumen,
separated from endothelium by a slower moving clear zone ofseparated from endothelium by a slower moving clear zone of
plasma. Stasis and turbulence then leads to thrombosis inplasma. Stasis and turbulence then leads to thrombosis in
following manner:following manner:
a. They disrupt laminar blood flow and bring platelets ina. They disrupt laminar blood flow and bring platelets in
contact with the endothelium.contact with the endothelium.
b. They prevent dilution of activated clotting factors byb. They prevent dilution of activated clotting factors by
freshfresh
flowing blood.flowing blood.
c. They retard the inflow of clotting factor inhibitors andc. They retard the inflow of clotting factor inhibitors and
permit the build up of thrombi.permit the build up of thrombi.
d. Promote endothelial cell activation, predisposing to locald. Promote endothelial cell activation, predisposing to local
thrombosis.thrombosis.

III.III.HYPERCOAGULABILITYHYPERCOAGULABILITY
Hypercoagulability contributes less frequently to thrmobotic states but it is anHypercoagulability contributes less frequently to thrmobotic states but it is an
important component in thrombosis. It is defined asimportant component in thrombosis. It is defined as any alteration in theany alteration in the
coagulation pathway that predisposes to thrombosiscoagulation pathway that predisposes to thrombosis
It can be divided into primary (genetic) and secondary (acquired) disordersIt can be divided into primary (genetic) and secondary (acquired) disorders
PRIMARY (Genetic) HYPERCOAGULABLE STATES:PRIMARY (Genetic) HYPERCOAGULABLE STATES:
 Mutations in Factor V (Factor V Leiden)Mutations in Factor V (Factor V Leiden)
 Antithrombin III deficiencyAntithrombin III deficiency
 Protein C or S deficiencyProtein C or S deficiency
 HomocystenemiaHomocystenemia
 Allelic variation in Prothrombin levelAllelic variation in Prothrombin level
SECONDARY (Acquired) HYPERCOAGULABLE STATES:SECONDARY (Acquired) HYPERCOAGULABLE STATES:
 Prolonged bed rest or immobilizationProlonged bed rest or immobilization
 Myocardial infarctionMyocardial infarction
 Tissue damage( Surgery, fracture, burn)Tissue damage( Surgery, fracture, burn)
 CancerCancer
 Antiphospholipid Antibody syndrome (Lupus Anticoagulant)Antiphospholipid Antibody syndrome (Lupus Anticoagulant)
 Oral ContraceptivesOral Contraceptives
 SmokingSmoking
 Heparin Induced Thrombocytpenia with Thrombosis (HITT)Heparin Induced Thrombocytpenia with Thrombosis (HITT)

9898
InheritedInherited TThrombophiliahrombophilia
-- Factor V Leiden mutationFactor V Leiden mutation
(Resistance to activated protein C)(Resistance to activated protein C)
- Prothrombin gene mutation- Prothrombin gene mutation
((Hyperprothrombinemia -Hyperprothrombinemia - prothrombin variant G20210Aprothrombin variant G20210A))
- Protein S deficiency- Protein S deficiency
- Protein C deficiency- Protein C deficiency
- Antithrombin (AT) deficiency- Antithrombin (AT) deficiency
- Dysfibrinogenemia- Dysfibrinogenemia
- Hyperhomocysteinemia- Hyperhomocysteinemia

9999
AcquiredAcquired Hypercoagulable DHypercoagulable Disordersisorders
 MalignancyMalignancy
 Presence of a central venousPresence of a central venous
cathetercatheter
 Surgery, especially orthopedicSurgery, especially orthopedic
 TraumaTrauma
 ImmobilizationImmobilization
 Congestive failureCongestive failure
 PregnancyPregnancy
 Oral contraceptivesOral contraceptives
 Hormone replacement therapyHormone replacement therapy
 Antiphospholipid antibodyAntiphospholipid antibody
syndromesyndrome
 Myeloproliferative disordersMyeloproliferative disorders
 Polycythemia veraPolycythemia vera
 Essential thrombocythemiaEssential thrombocythemia
 Paroxysmal nocturnalParoxysmal nocturnal
hemoglobinuriahemoglobinuria
 Tamoxifen, Thalidomide,Tamoxifen, Thalidomide,
LenalidomideLenalidomide
 Inflammatory bowel diseaseInflammatory bowel disease
 Nephrotic syndromeNephrotic syndrome

Mutations in Factor V Laiden:Mutations in Factor V Laiden:
 There is a substutitution for the normal argenine residue atThere is a substutitution for the normal argenine residue at
position 506 of factor V.position 506 of factor V. Due to this mutation factor VDue to this mutation factor V
cannot be inactivated by cleavage at the usual argininecannot be inactivated by cleavage at the usual arginine
residue and is therefore resistant to anticoagulantresidue and is therefore resistant to anticoagulant
effect of activated protein C.effect of activated protein C.
 The patients with this mutation usually present with recurrentThe patients with this mutation usually present with recurrent
thrombosis and recurrent abortionsthrombosis and recurrent abortions
Primary (Genetic) Hypercoagulable StatesPrimary (Genetic) Hypercoagulable States

Antithrombin III, Protein C and S DeficiencyAntithrombin III, Protein C and S Deficiency::

Patients with this deficiency usually present withPatients with this deficiency usually present with
deep venous thrombosis and recurrentdeep venous thrombosis and recurrent
thromboembolism in adolescence or early adult life.thromboembolism in adolescence or early adult life.

103103
Prothrombin Gene MutationProthrombin Gene Mutation
 A single –nucleotide substitution (G to A) in the 3 ‘ –untranslatedA single –nucleotide substitution (G to A) in the 3 ‘ –untranslated
region of the prothrombin gene is a fairly common alleleregion of the prothrombin gene is a fairly common allele
 This variant results in increased prothrombin transcription and isThis variant results in increased prothrombin transcription and is
associated with a nearly three fold increased risk for venousassociated with a nearly three fold increased risk for venous
thormbosesthormboses
 Prothrombin (factor II) is the precursor of thrombin, the end-Prothrombin (factor II) is the precursor of thrombin, the end-
product of the coagulation cascadeproduct of the coagulation cascade
 Heterozygous carriers have 30Heterozygous carriers have 30%% higher plasma prothrombin levelshigher plasma prothrombin levels
than normalsthan normals
 Heterozygous carriers haveHeterozygous carriers have an increased risk of deep vein andan increased risk of deep vein and
cerebral vein thrombosiscerebral vein thrombosis

104104
Hereditary thrombophiliaHereditary thrombophilia
 Characteristics:Characteristics:
- thrombosis without any predisposing conditionthrombosis without any predisposing condition
- thrombosis at young agethrombosis at young age
- thrombosis in unusual sitesthrombosis in unusual sites
(upper extremities, mesenteric vessels, hepatic or portal veins)(upper extremities, mesenteric vessels, hepatic or portal veins)
- family history of thrombosisfamily history of thrombosis
Neonatal purpura fulminans (homozygous PC or PS deficiency)Neonatal purpura fulminans (homozygous PC or PS deficiency)

Antiphospohlipid Antibody SyndromeAntiphospohlipid Antibody Syndrome::
Anti-phospohlipid antibodies are directed againstAnti-phospohlipid antibodies are directed against
epitopes on the surface of plasma proteins. Theseepitopes on the surface of plasma proteins. These
antibodies produce hyper-coagulable state by directantibodies produce hyper-coagulable state by direct
platelet activation, inhibition of prostacyclin, andplatelet activation, inhibition of prostacyclin, and
interference in Protein C synthesis. The patients withinterference in Protein C synthesis. The patients with
these antibodies usually present with recurrentthese antibodies usually present with recurrent
thrombosis and repeated miscarriagesthrombosis and repeated miscarriages
Acquired (Secondary ) Hypercoagulable StatesAcquired (Secondary ) Hypercoagulable States

Oral Contraceptives Use and Pregnancy:Oral Contraceptives Use and Pregnancy:
 In these conditions there is increased hepatic synthesisIn these conditions there is increased hepatic synthesis
of many coagulant factors and reduced synthesis ofof many coagulant factors and reduced synthesis of
antithronbin IIIantithronbin III

Heparin Induced Thrombocytopenia with ThrombosisHeparin Induced Thrombocytopenia with Thrombosis
(HITT)(HITT)
 Occurs in 5% patients treated with unfracftionatedOccurs in 5% patients treated with unfracftionated
heparin (for therapeutic anticoagulation)heparin (for therapeutic anticoagulation)
 Antibodies are formed against heprin and plateletAntibodies are formed against heprin and platelet
membrane protein (platelet factor 4)membrane protein (platelet factor 4)
 These antibodies may also bind similar complexesThese antibodies may also bind similar complexes
present on platelet and endothelial surfaces , resultingpresent on platelet and endothelial surfaces , resulting
in platelet activation, aggregation and consumptionin platelet activation, aggregation and consumption
(hence Thrombocytopenia), as well as causing(hence Thrombocytopenia), as well as causing
endothelial injuryendothelial injury

Overall result is aOverall result is a pro-thrombotic state, evenpro-thrombotic state, even
in the face of heparin administration andin the face of heparin administration and
low platelet countlow platelet count

TYPES OF THROMBITYPES OF THROMBI
A thrombus is easily recognized as a solid mass in the lumen of aA thrombus is easily recognized as a solid mass in the lumen of a
blood vessel that is often attached to the vessel wall.blood vessel that is often attached to the vessel wall.
PALE THORMBIPALE THORMBI RED THROMBIRED THROMBI
Thrombi in the fastThrombi in the fast
flowingflowing arterialarterial
circulationcirculation areare
composed predominantlycomposed predominantly
of fibrin and platelets,of fibrin and platelets,
with few entrappedwith few entrapped
erythrocytes – hence theerythrocytes – hence the
term Pale Thrombusterm Pale Thrombus
Typically occurs inTypically occurs in
venous circulationvenous circulation ,,
where the slowerwhere the slower
blood flow encouragesblood flow encourages
entrapment of redentrapment of red
cells. They arecells. They are
composed of platelets,composed of platelets,
fibrin and largefibrin and large
numbers ofnumbers of
erythrocytes trappederythrocytes trapped
in the fibrin mesh.in the fibrin mesh.

SITES OF THROMBOSISSITES OF THROMBOSIS
I.I. ARTERIAL THROMBOSIS:ARTERIAL THROMBOSIS:
Arterial thrombosis is common and typically occurs afterArterial thrombosis is common and typically occurs after
endothelial damage and local turbulence has been caused byendothelial damage and local turbulence has been caused by
atheroscleorsis.Large and medium sized arteries such as the aorta,atheroscleorsis.Large and medium sized arteries such as the aorta,
carotid arteries, arteries of circle of Willis, coronary arteries, andcarotid arteries, arteries of circle of Willis, coronary arteries, and
arteries of the intestine and limbs are mainly affectedarteries of the intestine and limbs are mainly affected
Mural Thrombi:Mural Thrombi: When arterial thrombi arise in heart chambers or inWhen arterial thrombi arise in heart chambers or in
aortic lumen, they are usually adherent to the wall of underlyingaortic lumen, they are usually adherent to the wall of underlying
structure and are termed Mural Thrombi.structure and are termed Mural Thrombi.
Lines of Zahn: When arterial thrombus is
formed in the heart or aorta, thrombi may
have grossly (and microscopically) apparent
laminations called lines of Zahn; these are
produced by alternating pale layers of
platelets admixed with some fibrin and
darker layers containing more red blood
cells

II.II.VENOUS THROMBOSISVENOUS THROMBOSIS
1.1. PHLEBOTHROMBOSISPHLEBOTHROMBOSIS :: It denotes venous thrombosis occurring inIt denotes venous thrombosis occurring in
the absence of obvious inflammation. Phlebothrombosis occursthe absence of obvious inflammation. Phlebothrombosis occurs
mostlymostly in deep veins of the legin deep veins of the leg ((Deep Venous Thrombosis ; DVT)Deep Venous Thrombosis ; DVT)
Deep venous thrombosis is common and
has important medical implications because
the large thrombi that form in these veins
are often easily detached. They travel in
the circulation to the heart and lung and
lodge in the pulmonary arteries (Pulmonary
Embolism)
Venous Thrombus in Femoral Vein: Femoral
vein opened to reveal a thrombus

2.2. THROMBOPHELIBITISTHROMBOPHELIBITIS :: It denotes venous thrombosisIt denotes venous thrombosis
occurring secondary to acute inflammation .occurring secondary to acute inflammation .
Thrombophelibitis is a common phenomenon in infectedThrombophelibitis is a common phenomenon in infected
wounds or ulcers and characteristically involves thewounds or ulcers and characteristically involves the
superficial veins and the extremities . The effected veinsuperficial veins and the extremities . The effected vein
is firm and cord like and shows signs of acuteis firm and cord like and shows signs of acute
inflammation (pain, redness, warmth, swelling). This typeinflammation (pain, redness, warmth, swelling). This type
of thrombus is firmly attached to the vessel wall and theyof thrombus is firmly attached to the vessel wall and they
rarely embolize.rarely embolize.

III.III. CARDIAC THROMBOSISCARDIAC THROMBOSIS
In Different circumstances Thrombi are formed inIn Different circumstances Thrombi are formed in
different locations inside the heart:different locations inside the heart:
1.1. Thrombi may occur in ventricles after MyocardialThrombi may occur in ventricles after Myocardial
InfarctionInfarction
2.2. Thrombi may occur in Atria in Atrial FibrillationThrombi may occur in Atria in Atrial Fibrillation
3.3. Thrombi may be formed in Heart Valves in RheumaticThrombi may be formed in Heart Valves in Rheumatic
Endocarditic or in Infective EndocarditicEndocarditic or in Infective Endocarditic

FATE OF THROMBOSISFATE OF THROMBOSIS
If a patient survives the immediate effects of a thromboticIf a patient survives the immediate effects of a thrombotic
vascular obstruction, thrombi undergo some combination of thevascular obstruction, thrombi undergo some combination of the
following five events in the ensuing days or weeksfollowing five events in the ensuing days or weeks

Thrombus- FateThrombus- Fate
•PropagationPropagation
•EmbolizationEmbolization
•DissolutionDissolution
•Organization and RecanalizationOrganization and Recanalization

1. Lysis of the thrombosis and complete
resolution of normal structure usually
can occur only when the thrombus is
relatively small and is dependent upon
the activity of Fibrinolytic System
2. Organization : The
thrombus may be replaced by scar tissue which
contracts and obliterates the lumen;
the blood bypasses the occluded vessel
through collateral circulation
3. Dystrophic Calcification
4. Recanalization: Occasionally some of
the capillaries dilate and allow the
passage of blood through the thrombus
or the fibrosed thrombus shrinks from
the vascular wall leaving a space which
gets lined by endothelium.
5.Propagation: The thrombus may
accumulate more platelets and fibrin and eventually leads to vessel
obstruction

5. Emoblization: Emboli can result from fragmentation of the thrombus and
can result in infarction at a distant site

THROMBUSTHROMBUS CLOTCLOT
Occurs inside cardiovascularOccurs inside cardiovascular
systemsystem
Occurs inside or outside theOccurs inside or outside the
cardiovascular systemcardiovascular system
Occurs during life in circulatingOccurs during life in circulating
bloodblood
Occurs during life or after deathOccurs during life or after death
in stagnant bloodin stagnant blood
Contains platelets ( e.g., lines ofContains platelets ( e.g., lines of
Zhan)Zhan)
No plateletsNo platelets
FirmFirm SoftSoft
Firmly adherent to theFirmly adherent to the
cardiovascular sitecardiovascular site
Loosely adherentLoosely adherent
Pale, red or mixedPale, red or mixed Red or yellowRed or yellow

Thrombosis – Summary
A thrombus is a solid mass of blood constituents formed
within the vascular system in life.
Predisposing factors (Virchow’s triad) :abnormalities of
the vessel wall; abnormalities of blood flow;
abnormalities of the blood constituents.
Arterial thrombosis is most commonly superimposed on
athermoa
Venous thrombosis is most commonly due to stasis
Clinical consequences include: arterial thrombosis (tissue
infarction distally); venous thrombosis (oedema, due to
impaired venous drainage); and embolism

EMBOLISMEMBOLISM
••““An Embolus is a detached intravascular solid,An Embolus is a detached intravascular solid,
liquid or gaseous mass that is carried by the bloodliquid or gaseous mass that is carried by the blood
to a site distant from its point of origin”to a site distant from its point of origin”
••Virtually 99% of the emboli represent some part of aVirtually 99% of the emboli represent some part of a
dislodged thrombus, hence the commonly used termdislodged thrombus, hence the commonly used term
ThromboembolismThromboembolism..
••Inevitably, emboli lodge in vessels too small to permitInevitably, emboli lodge in vessels too small to permit
further passage, resulting in partial or complete vascularfurther passage, resulting in partial or complete vascular
occlusion. The potential consequences of suchocclusion. The potential consequences of such
thromboembolic events is the ischemic necrosis of distalthromboembolic events is the ischemic necrosis of distal
tissue known astissue known as InfarctionInfarction

ThrombosisThrombosis
EmbolismEmbolism
Emboli lodge in vessels too smallEmboli lodge in vessels too small
to permit further passageto permit further passage
Partial or complete vascular occlusionPartial or complete vascular occlusion

TYPES OF EMBOLITYPES OF EMBOLI
1.1. ThromboembolismThromboembolism
(i) Pulmonary Thromboembolism(i) Pulmonary Thromboembolism
(ii) Systemic Thromboembolism(ii) Systemic Thromboembolism
2.2. Fat EmbolismFat Embolism
33. Air Embolism. Air Embolism
4.4. Amniotic Fluid EmbolismAmniotic Fluid Embolism
5.5. Nitrogen Gas Embolism (Decompression Sickness)Nitrogen Gas Embolism (Decompression Sickness)

I.I. PULMONARY THROMBOEMBOLISMPULMONARY THROMBOEMBOLISM
Cause and Incidence:Cause and Incidence: The most serious form ofThe most serious form of
thrombembolism is pulmonary embolism, which maythrombembolism is pulmonary embolism, which may
cause sudden death. It has an incidence of 20 to 25 percause sudden death. It has an incidence of 20 to 25 per
100,000 hospitalized patients100,000 hospitalized patients
Over 90% of Pulmonary Emboli originate in the deep veinsOver 90% of Pulmonary Emboli originate in the deep veins
of the leg (phelebothrombosis)of the leg (phelebothrombosis) .. More rarely, thrombi inMore rarely, thrombi in
pelvic venous plexus are the source.pelvic venous plexus are the source.
Pulmonary embolism is common in the following conditionsPulmonary embolism is common in the following conditions
that predispose to the development of phlebothrombosis:that predispose to the development of phlebothrombosis:
(i)(i) Immediate post operative periodImmediate post operative period
(ii)(ii) Immediate post partum periodImmediate post partum period
(iii)(iii) Lengthy immobilization in bedLengthy immobilization in bed
(iv)(iv) Cardiac FailureCardiac Failure
(v)(v) use of Oral Contraceptivesuse of Oral Contraceptives

CLINICAL EFFECTS OF PULMONARY EMBOLISMCLINICAL EFFECTS OF PULMONARY EMBOLISM
The size of the embolus is the factor most influencing theThe size of the embolus is the factor most influencing the
clinical effects of pulmonary embolismclinical effects of pulmonary embolism
1.1. Massive Emboli:Massive Emboli: Large emboli (several centimeter long)Large emboli (several centimeter long)
maymay lodge in the outflow tract of the right ventricle or inlodge in the outflow tract of the right ventricle or in
the main pulmonary artery,the main pulmonary artery, where they cause circulatorywhere they cause circulatory
obstruction andobstruction and Sudden DeathSudden Death ..
2.2. Medium Sized Emboli:Medium Sized Emboli: obstruction of medium sizedobstruction of medium sized
arteriesarteries may causemay cause Pulmonary InfarctPulmonary Infarct
3.3. Small Emboli:Small Emboli: Small emboli lodge in minor branches ofSmall emboli lodge in minor branches of
pulmonary artery with no immediate effects. In manypulmonary artery with no immediate effects. In many
instances, the emboli either fragment soon afterinstances, the emboli either fragment soon after
lodgment of dissolve during fibrinolysis, in which caselodgment of dissolve during fibrinolysis, in which case
clinical effects are minimal. If numerous small emboliclinical effects are minimal. If numerous small emboli
occur over a long period, however, the pulmonaryoccur over a long period, however, the pulmonary
microcirculation may be so severely compromised thatmicrocirculation may be so severely compromised that
Pulmonary Hypertension resultsPulmonary Hypertension results

II.II.SYSTEMIC THROMBOEMBOLISMSYSTEMIC THROMBOEMBOLISM
Causes:Causes:Thromboembolism occurs in systemic arteries whenThromboembolism occurs in systemic arteries when
the detached thrombus originates in the left side of thethe detached thrombus originates in the left side of the
heart or a large artery.heart or a large artery.
Systemic arterial thromboembolism commonly occurs:Systemic arterial thromboembolism commonly occurs:
1.1. In patients who have infective endocarditic withIn patients who have infective endocarditic with
vegetations on the mitral and aortic valves.vegetations on the mitral and aortic valves.
2.2. In patients who have suffered myocardial infarction inIn patients who have suffered myocardial infarction in
which mural thrombus has occurred.which mural thrombus has occurred.
3.3. In patients with mitral stenosis and arterial thrombosis.In patients with mitral stenosis and arterial thrombosis.
4.4. In patients with aortic and ventricular aneurysms, whichIn patients with aortic and ventricular aneurysms, which
contain mural thrombicontain mural thrombi

Clinical Effects of Systemic Thromboembolism:Clinical Effects of Systemic Thromboembolism:
In contrast to venous emboli,which tend to lodgeIn contrast to venous emboli,which tend to lodge
primarily in one vascular bed (the lung), arterial emboliprimarily in one vascular bed (the lung), arterial emboli
can travel to a wide variety of sites . The site of arrestcan travel to a wide variety of sites . The site of arrest
depends on the point of origin of the thromboembolismdepends on the point of origin of the thromboembolism
and the volume of blood flow through the down streamand the volume of blood flow through the down stream
tissues. The major sites for arterial embolization are thetissues. The major sites for arterial embolization are the
lower extremities (75%) and the brain (10%)., withlower extremities (75%) and the brain (10%)., with
intestines, kidneys, spleen and upper extremitiesintestines, kidneys, spleen and upper extremities
involved to a lesser extent.involved to a lesser extent.
The consequences of systemic emboli depend onThe consequences of systemic emboli depend on
any collateral vascular supply in the affected tissue, theany collateral vascular supply in the affected tissue, the
tissue vulnerability to ischemia, and the caliber of thetissue vulnerability to ischemia, and the caliber of the
vessel occluded. In general, however, arterial embolivessel occluded. In general, however, arterial emboli
cause infarction of tissues in the distributution of thecause infarction of tissues in the distributution of the
obstructed vessel.obstructed vessel.

III.III.FAT EMBOLISMFAT EMBOLISM
Causes:Causes: Fat Embolism occurs when globules of fat enter theFat Embolism occurs when globules of fat enter the
bloodstream, typicallybloodstream, typically after fractures of large bones(eg,after fractures of large bones(eg,
femur) have exposed the fatty bone marrowfemur) have exposed the fatty bone marrow .. Although fatAlthough fat
globules can be found in the circulation in as many asglobules can be found in the circulation in as many as
90% of patients who have sustained serious fractures,90% of patients who have sustained serious fractures,
few patients demonstrate clinically significant signs of fatfew patients demonstrate clinically significant signs of fat
embolism.embolism.
Clinical Effects of Fat Embolism:Clinical Effects of Fat Embolism: Fat embolism syndromeFat embolism syndrome
typically begins 1 to 3 days after injury, with suddentypically begins 1 to 3 days after injury, with sudden
onset of tachypnea, dyspnea and tachycardia . Besidesonset of tachypnea, dyspnea and tachycardia . Besides
pulmonary insufficiency, the syndrome is characterized bypulmonary insufficiency, the syndrome is characterized by
neurological symptoms,including irritability andneurological symptoms,including irritability and
restlessness, which can prgress to delirium or coma. Arestlessness, which can prgress to delirium or coma. A
diffuse petechial rash in non dependent areas occurringdiffuse petechial rash in non dependent areas occurring
in the absence of thrombocytopenia is seen in 20 to 30%in the absence of thrombocytopenia is seen in 20 to 30%
of cases and is useful in establishing a diagnosis.of cases and is useful in establishing a diagnosis.
The typical clinical features of fat embolism include aThe typical clinical features of fat embolism include a
Haemorrhagic skin rash, dyspnea, tachycardia,Haemorrhagic skin rash, dyspnea, tachycardia,
tachypnea, irritability and restlessness.tachypnea, irritability and restlessness.

IV.IV.AIR EMBOLISMAIR EMBOLISM
CAUSESCAUSES::
a.a. Surgery of or Trauma to internal Jugular vein:Surgery of or Trauma to internal Jugular vein: In injuriesIn injuries
to the internal jugular vein, the negative pressure in theto the internal jugular vein, the negative pressure in the
thorax tends to suck air into the jugular vein. Thisthorax tends to suck air into the jugular vein. This
phenomenon does not occur in injuries to other systemicphenomenon does not occur in injuries to other systemic
veins because they are separated by valves from theveins because they are separated by valves from the
negative pressure in the chestnegative pressure in the chest
b.b. Child birth or Abortion:Child birth or Abortion: Air embolism may occur duringAir embolism may occur during
childbirth or abortion, when air may be forced intochildbirth or abortion, when air may be forced into
ruptured placental venous sinuses by forcefulruptured placental venous sinuses by forceful
contractions of uterus.contractions of uterus.
c.c. Blood Transfusion:Blood Transfusion: Air embolism during blood transfusionAir embolism during blood transfusion
occurs only if positive pressure is used to transfuse theoccurs only if positive pressure is used to transfuse the
blood and only if the transfusion is not discontinued atblood and only if the transfusion is not discontinued at
its completion.its completion.
Clinical Effects of Air Embolism:Clinical Effects of Air Embolism: When air enters the bloodWhen air enters the blood
stream, it passes into the right ventricle, creating a frothystream, it passes into the right ventricle, creating a frothy
mixture that effectively obstructs the circulation andmixture that effectively obstructs the circulation and
causes death.causes death.

V.V.NITROGEN GAS EMBOLISMNITROGEN GAS EMBOLISM
(DECOMPRESSION SICKNESS)(DECOMPRESSION SICKNESS)
CAUSE:CAUSE: Decompression sickness is a form of embolism thatDecompression sickness is a form of embolism that
occurs in Caisson workers and undersea divers if theyoccurs in Caisson workers and undersea divers if they
ascend too rapidly after being submerged for longascend too rapidly after being submerged for long
periods. This disorder is also called theperiods. This disorder is also called the BendsBends oror
Caisson DiseaseCaisson Disease ..
(Caissons are high pressure underwater chambers used for(Caissons are high pressure underwater chambers used for
deep water construction work)deep water construction work)
When air is breathed under high underwaterWhen air is breathed under high underwater
pressure, an increased volume of air, mainly oxygen andpressure, an increased volume of air, mainly oxygen and
nitrogen, goes into solution in the blood and equilibratesnitrogen, goes into solution in the blood and equilibrates
with the tissues . If decompression to sea level is toowith the tissues . If decompression to sea level is too
rapid, the gases that equilibrated in the tissues come outrapid, the gases that equilibrated in the tissues come out
of solution. Oxygen is rapidly absorbed into the blood,of solution. Oxygen is rapidly absorbed into the blood,
but nitrogen gas coming out of solution can not bebut nitrogen gas coming out of solution can not be
absorbed rapidly enough and forms bubbles in theabsorbed rapidly enough and forms bubbles in the
tissues and blood stream that acts as emboli.tissues and blood stream that acts as emboli.

Clinical Effects of Nitrogen Gas EmbolismClinical Effects of Nitrogen Gas Embolism
Platelets adhere to nitrogen gas bubbles in thePlatelets adhere to nitrogen gas bubbles in the
circulation an activate coagulation cascade. The resultingcirculation an activate coagulation cascade. The resulting
disseminated intravascular coagulation aggravates thedisseminated intravascular coagulation aggravates the
ischemic state caused by impaction of gas bubbles inischemic state caused by impaction of gas bubbles in
capillaries. Involvement of brain in severe cases maycapillaries. Involvement of brain in severe cases may
cause extensive necrosis and death. In less severecause extensive necrosis and death. In less severe
cases, nerve and muscle involvement causescases, nerve and muscle involvement causes severesevere
muscle contractions with intense pain (the bends)muscle contractions with intense pain (the bends) ..
Nitrogen gas emboli in lungs causeNitrogen gas emboli in lungs cause Severe difficulty inSevere difficulty in
breathing (the chokes)breathing (the chokes) that is associated with alveolarthat is associated with alveolar
edema and haemorrhageedema and haemorrhage

VI.VI. AMNIOTIC FLUID EMBOLISMAMNIOTIC FLUID EMBOLISM
Cause:Cause: The underlying cause is infusion of amniotic fluidThe underlying cause is infusion of amniotic fluid
into the maternal circulation via a tear in the placentalinto the maternal circulation via a tear in the placental
membranes and rupture of uterine veins.membranes and rupture of uterine veins.
Clinical Effects:Clinical Effects: Amniotic Fluid Embolism is a grave butAmniotic Fluid Embolism is a grave but
uncommon complication of labour and the immediateuncommon complication of labour and the immediate
postpartum period. It has a mortality of over 80%.Withpostpartum period. It has a mortality of over 80%.With
the vastly increased pressures in the uterus duringthe vastly increased pressures in the uterus during
labour, amniotic fluid may be forced into the maternallabour, amniotic fluid may be forced into the maternal
uterine veins. These amniotic fluid emboli travel in theuterine veins. These amniotic fluid emboli travel in the
circulation and lodge in the lungs, causing respiratorycirculation and lodge in the lungs, causing respiratory
distress. The onset is characterized by sudden severedistress. The onset is characterized by sudden severe
dyspnea, cyanosis, and hypotensive shock, followed bydyspnea, cyanosis, and hypotensive shock, followed by
seizures and coma.seizures and coma.

AMNIOTIC FLUID EMBOLISM
Two small pulmonary arterioles are packed with laminated swirls of foetal squamous cells. There is marked
edema and congestion and elsewhere in the lung tissue there are small orgainzing thrombi , consistent with
disseminated intravascular coagulation.

SummarySummary
•• An Embolus is a mass of material in the vascularAn Embolus is a mass of material in the vascular
system able to become lodged within a vessel andsystem able to become lodged within a vessel and
block its lumen.block its lumen.
•• Most Emboli are derived from Thrombi.Most Emboli are derived from Thrombi.
••Other types of embolic material include: AtheromatousOther types of embolic material include: Atheromatous
plaque material, Vegetations on heart valves(infectiveplaque material, Vegetations on heart valves(infective
endocarditic), Amniotic Fluid , Gas and Fat.endocarditic), Amniotic Fluid , Gas and Fat.
••Most common occurrence is Pulmonary Embolism fromMost common occurrence is Pulmonary Embolism from
deep leg vein thrombosisdeep leg vein thrombosis

INFARCTIONINFARCTION
Definition:Definition: An Infarct is an area of ischemicAn Infarct is an area of ischemic
necrosis caused by occlusion of either thenecrosis caused by occlusion of either the
arterial supply or venous drainage in aarterial supply or venous drainage in a
particular tissueparticular tissue
Nearly 99% of all infarcts result from thrombosis orNearly 99% of all infarcts result from thrombosis or
embolic events and almost all result from arterialembolic events and almost all result from arterial
occlusion. More rarely, obstruction of venous drainageocclusion. More rarely, obstruction of venous drainage
results in infarction.results in infarction.
Tissue infarction is a common and extremelyTissue infarction is a common and extremely
important cause of clinical illness. Important clinicalimportant cause of clinical illness. Important clinical
entities which are attributable to infarction are:entities which are attributable to infarction are:
1.1. Myocardial InfarctionMyocardial Infarction
2.2. Cerebral InfarctionCerebral Infarction
3.3. Pulmonary InfarctionPulmonary Infarction
4.4. Intestinal InfarctionIntestinal Infarction

CLASSIFICATION OF TYPES OF INFARCTCLASSIFICATION OF TYPES OF INFARCT
The appearance of infarcts varies with the site .The appearance of infarcts varies with the site .
Various classification schemes are usedVarious classification schemes are used
A.A. PALE Versus RED INFARCTPALE Versus RED INFARCT
B.B. SOLID Versus LIQUIFIED INFARCTSOLID Versus LIQUIFIED INFARCT
C.C. STERILE Versus SEPTIC INFARCTSTERILE Versus SEPTIC INFARCT

A.A. PALE Versus RED INFARCTPALE Versus RED INFARCT
Pale Infarct:Pale Infarct: Occur as a result of arterial obstruction in solidOccur as a result of arterial obstruction in solid
organs such as heart, kidney, spleen and brain. Theseorgans such as heart, kidney, spleen and brain. These
organs lack significant collateral circulation, and theorgans lack significant collateral circulation, and the
solidity of the tissue limits the amount of haemorrhagesolidity of the tissue limits the amount of haemorrhage
that can seep into the area of ischemic necrosis fromthat can seep into the area of ischemic necrosis from
adjoining capillary bedsadjoining capillary beds
Red or Haemorrhagic Infarct:Red or Haemorrhagic Infarct:
(i) In tissues that have a double blood supply , e.g., lung,(i) In tissues that have a double blood supply , e.g., lung,
intestines and liver permitting some continued flow intointestines and liver permitting some continued flow into
the area although the amount is not sufficient to preventthe area although the amount is not sufficient to prevent
infarction . The infarct is red because of extravasation ofinfarction . The infarct is red because of extravasation of
blood in the infarcted area from necrotic small vessels.blood in the infarcted area from necrotic small vessels.
(ii) With venous occlusion (such as in ovarian torsion)(ii) With venous occlusion (such as in ovarian torsion)
(iii) In loose tissues (such as lung), which allow blood to(iii) In loose tissues (such as lung), which allow blood to
collect in the infarcted zone.collect in the infarcted zone.
(iv) In tissues that were previously congested because of(iv) In tissues that were previously congested because of
sluggish venous outflowsluggish venous outflow
(v) When flow is reestablished to a site of previous arterial(v) When flow is reestablished to a site of previous arterial
occlusionocclusion

B .B . SOLID Versus LIQUEFIED INFARCTSOLID Versus LIQUEFIED INFARCT
In all tissues other than brain, infarction usuallyIn all tissues other than brain, infarction usually
produces coagulative necrosis of cells, leading to solidproduces coagulative necrosis of cells, leading to solid
infarct. In brain, on the other hand, liquefactive necrosisinfarct. In brain, on the other hand, liquefactive necrosis
of cells leads to the formation of a fluid mass in the areaof cells leads to the formation of a fluid mass in the area
of infarction. The end result is a cystic cavityof infarction. The end result is a cystic cavity
C.C. STERILE Versus SEPTIC INFARCTSTERILE Versus SEPTIC INFARCT
Most infarcts are sterile. Septic infarcts areMost infarcts are sterile. Septic infarcts are
characterized by secondary bacterial infection of thecharacterized by secondary bacterial infection of the
necrotic tissue. Septic infarcts are characterized by acutenecrotic tissue. Septic infarcts are characterized by acute
inflammation that frequently converts the infarcts to aninflammation that frequently converts the infarcts to an
abscess. Secondary bacterial infection of an infarct mayabscess. Secondary bacterial infection of an infarct may
also result in gangrene (e.g., intestine).also result in gangrene (e.g., intestine).
Septic infarcts occur:Septic infarcts occur:
1. Due to presence of microorganisms, as in lesions of1. Due to presence of microorganisms, as in lesions of
infective endocarditisinfective endocarditis
2. When infarction occurs in a tissue that normally contain2. When infarction occurs in a tissue that normally contain
bacteria , e.g., intestinebacteria , e.g., intestine

MORPHOLOGY OF INFARCTSMORPHOLOGY OF INFARCTS
●●Infarction occurs in tissue supplied by anInfarction occurs in tissue supplied by an
artery that, when occluded leaves anartery that, when occluded leaves an
insufficient collateral blood supply. Infarctsinsufficient collateral blood supply. Infarcts
in kidney, spleen and lungs arein kidney, spleen and lungs are WedgeWedge
ShapedShaped ,, with the occluded artery situatedwith the occluded artery situated
near the apex of the wedge and the base ofnear the apex of the wedge and the base of
the infarct located on the surface of thethe infarct located on the surface of the
organorgan . The characteristic shape of infarcts. The characteristic shape of infarcts
in these organs is due to symmetricin these organs is due to symmetric
dichotomous branching pattern of thedichotomous branching pattern of the
arteries supplying them.arteries supplying them.
●The cerebral and myocardial infarcts are irregular
shaped and determined by the distribution of the
occluded artery and the limits of collateral arterial supply.

Infarct of Intestine: Infarction may
follow thrombosis of or embolization
to the mesenteric arteries. The
sequence of changes usually seen in
solid organs is altered by the effects
of anastomosis and, in later stages
by Bacterial Invasion
Infarct of Heart (Myocardial Infarction)
Evolution of Myocardial Infarction: Changes are not evident in the initial
hours. The dead tissue elicits an inflammatory reaction, characterized first
by neutrophils then by macrophages. If no complications take place then
the infarct heals by fibrosis and scar is formed

Infarct of Brain: These are usually due to thrombosis of
diseased vessels or due to embolism from the left heart.
The usual changes of infarction takes place, but the
necrosis is liquefactive- cerebral softening.

EVOLUTION OF INFARCTEVOLUTION OF INFARCT
ThrombosisThrombosis
EmbolismEmbolism
Occlusion of Blood Supply (Ischemia)Occlusion of Blood Supply (Ischemia)
Necrosis of Parenchymal cells and Connective Tissue frame workNecrosis of Parenchymal cells and Connective Tissue frame work
( INFARCTION)( INFARCTION)
Inflammatory responseInflammatory response Superadded BacterialSuperadded Bacterial
Releases of Lysosomal EnzymesReleases of Lysosomal Enzymes
GangreneGangrene
Heterolysis or AutolysisHeterolysis or Autolysis
Macrophages Phagocytose liquefied debrisMacrophages Phagocytose liquefied debris
In growth of granulation TissueIn growth of granulation Tissue
Scar FormationScar Formation

Haemodynamic disorders , thromboembolism and shock by Dr Nadeem (RMC)

Haemodynamic disorders , thromboembolism and shock by Dr Nadeem (RMC)

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