Hemodynamic disorders (Edema, Hemorrhage, thrombosis, embolism)

1. Hemodynamic Disorders

2. Hemodynamics
• Hemodynamics, meaning literally "blood
movement" is the study of blood flow or the
circulation.
• It explains the physical laws that govern the
flow of blood in the blood vessels.

3. • The health of cells and tissues depends not only on an
intact circulation to deliver oxygen and remove
wastes but also on normal fluid homeostasis.
• Normal fluid homeostasis requires vessel wall
integrity as well as maintenance of intravascular
pressure and osmolarity within certain physiologic
ranges.

4. • Increases in vascular volume or pressure, decreases in
plasma protein content, or alterations in endothelial function
can result in a net outward movement of water across the
vascular wall.
• Such water extravasation into interstitial spaces is called
edema; depending on its location, edema may have minimal
or profound effects.
• Thus, in the lower extremities edema fluid causes
primarily swelling; however, in the lungs, edema fluid will fill
alveoli and can result in life-threatening breathing
difficulties.

5. • Normal fluid homeostasis also means maintaining blood as a
liquid until such time as injury necessitates formation of a
clot.
• Absence of clotting after vascular injury results in
hemorrhage; local bleeding can compromise regional tissue
perfusion, while more extensive hemorrhage can result in
hypotension (shock) and death.
• Conversely, inappropriate clotting (thrombosis) or
migration of clots (embolism) can obstruct tissue blood
supplies and cause cell death (infarction).
• Abnormal fluid homeostasis (i.e., hemorrhage or thrombosis)
underlies three of the most important causes of morbidity
and mortality : myocardial infarction, pulmonary embolism,
and cerebrovascular accident (stroke).

6. HYPEREMIA AND
CONGESTION

7. HYPEREMIA AND CONGESTION
• Both Hyperemia and Congestion
indicates a local increased volume of
blood in the tissue and organ.

8. HYPEREMIA
• It is an active process.
• It results from augmented blood flow due to
arteriolar dilation.
• The affected tissue is redder than normal because
of engorgement with oxygenated blood.
• E.g:
– Sites of inflammation.
– Skeletal muscle during exercise.
– Febrile condition and
– Blushing.

9. CONGESTION
• Congestion is a passive process
• It results from impaired venous return out of a tissue.
• Causes:
– Local venous compression
– Local venous obstruction
– Cardiac failure
• It may be -
– Systemic - In lung, liver and spleen.
– Local - Resulting from an isolated venous obstruction.
• The affected part shows Cyanosis. The color of blood in
congestion is blue red.

12. Hyperemia & Congestion
Normal Hyperemia Congestion

13. • Congestion of capillary beds is closely related to the
development of Edema, so that congestion and Edema
commonly occur together.
• In long-standing Congestion, called chronic passive
congestion, the stasis of poorly oxygenated blood causes
chronic hypoxia, which in turn can result in degeneration or
death of parenchymal cells and subsequent tissue fibrosis.
• Capillary rupture at such sites of chronic congestion can also
cause small foci of hemorrhage.
• Break down and phagocytosis of red cell debris can
eventually result in small clusters of hemosiderin-laden
macrophages.

14. Congestion of lung
• Seen mainly with left ventricular failure, e.g., myocardial
infarction, myocarditis, rheumatic heart disease with mitral
stenosis; mitral valve regurgitation.
• Acute pulmonary congestion
– The alveolar capillaries are engorged with blood.
– Associated alveolar septal Edema and focal intra alveolar
Hemorrhage.
– The break down and phagocytosis of red cell debris
eventually lead to the appearance of hemosiderin-laden
macrophages (heart failure cells) in the alveolar spaces.
• Chronic pulmonary congestion
– The septa become thickened and fibrotic, and the alveolar
spaces may contain numerous hemosiderin-laden
macrophages .

15. Normal lung, microscopically

16. Edema, lung, photomicrograph, LM

17. Congestive edema, HM

18. Heart failure cells
•hemosiderin

19. Microscopic : chronic lung congestion
Dilatation and congestion of alveolar septal capillary,
alveolar spaces contain exudation
H.E 10  10
Prussian blue 10  10
Heart failure
cell

20. Sketch map of alveolar septal capillary congestion
Normal
structure
Dilation and
congestion
of capillary
Fibrosis of alveolar septa
Chronic Lungs congestion: congestion and edema seen
mainly with left ventricular failure

21. Congestion of Liver
• Causes-
– Congestive heart failure (Rt sided heart
failure).
– Obstruction of IVC.
– Obstruction of hepatic vein.

22. Normal Histology of
Liver

23. three zones of the hepatic
lobules
•Portal
triads
•Central
vein

24. • Acute hepatic congestion-
– The Central vein and Sinusoids are distended with
blood.
– The Central hepatocyte show degeneration and the
peripheral hepatocyte show only fatty change.
** Better oxygenated because of their proximity to hepatic arterioles.

25. –Chronic hepatic congestion-
• In chronic passive congestion of the liver the central
regions of the hepatic lobules are grossly red-brown and
slightly depressed (because of a loss of cells) descriptively
referred to as “Nutmeg liver”.
• Microscopically-
– The centrilobular Necrosis with loss of hepatocytes (drop
out) and Hemorrhage including hemosiderin laden
macrophages.
– The peripheral hepatocytes, suffering from less severe
hypoxia, develop fatty change.

26. In this autopsy specimen, central areas
are red and slightly depressed compared
with the surrounding tan viable
parenchyma, creating “nutmeg liver”

27. Microscopic preparation shows centrilobular hepatic necrosis
with hemorrhage and scattered inflammatory cells.

28. EDEMA

29. Hemodynamic Disorders
EDEMA
• Approximately 60% of lean body weight is water, two-thirds
of which is intracellular and the remainder is in extracellular
compartments, mostly as interstitial fluid; only 5% of total
body water is in blood plasma.
• The term Edema signifies increased fluid in the interstitial
tissue spaces.
• Fluid collections in different body cavities are variously
designated hydrothorax, hydropericardium, or
hydroperitoneum.

30. Cell
Volume of normal body
fluid (about 60% of body weight)
interstitial
space
blood
vessel

31. • It is clinically evident when there is an excess of fluid by 10%.
• Ascites- It implies that there is excess fluid in the peritoneal
cavity.
• Hydrothorax- there is collection of excess fluid in the pleural
cavity.
• Hydropericardium- Accumulation of excess fluid in
peritoneal cavity.

33. • Concept
A large amount of body fluid accumulates in the interstitial space
interstitial
space Cell
Volume
of normal
body fluid
(about 60% of
body weight)
fluid
Edema
blood
vessel
(interstitial fluid↑) is edema .

34. • Imbalance of exchange between
intravascular and extravascular fluid
( Formation of interstitial fluid > back-flow. )
• Causes of Edema

35. 1、 Capillary blood
pressure↑
① Systemic venous
pressure↑
Heart failure
② Local venous
pressure↑
Tumor etc. press
vein.
Thrombosis etc.
obstruct vein.
(clinical common cause)
Venous pressure↑

36. 2、Plasma colloid osmotic
pressure ↓
Plasma albumin
Albumin↓
⑴ synthesize ↓
① liver disease
②serious protein
lack etc.
⑵ loss↑
① renal
diseases
② extensive burn
⑶ decomposition↑ chronic
infection
↓

37. 3、Capillary wall permeability↑
① Inflammatory responses
② Allergic responses
③ Hypoxia
etc.

38. • The mechanism of inflammatory
edema mostly involves increased
vascular permeability.

39. 血管内外液体交换示意图
淋巴管
Lymphatic tubule
4、Obstruction of lymphatic flow
① Filariasis
filaria
② Malignancy or
Surgery
Capillary

41. 淋巴管
capillary
1、Capillary blood （ hydrostatic） pressure↑
2、Plasma colloid osmotic pressure↓
3、Capillary wall permeability↑
4、Obstruction of lymphatic flow
Lymphatic tubule
interstitial fluid↑
Formation of interstitial fluid > back-flow
edema
→

42. 5. Retention of water and
sodium
– Excessive salt intake with renal insufficiency
– Increased tubular reabsorption of sodium
– Renal hypoperfusion
– Increased renin-angiotensin-aldosterone
secretion

46. Pathogenesis of edema:
• Cardiac edema-
– Rise in the central venous pressure, which is
transmitted, to the venous end of capillaries
causing transudation.
– Due to diversion of large amount of fluid to the
extravascular compartment give rise to
hypovolumia  increase ADH and
Aldosteron secretion  increase salt and
water retention  Edema formation.

47. Renal edema (Nephrotic syndrome)
• Massive proteinuria  hypoproteinaemia
decreased colloidal osmotic pressure diversion of
fluid from blood vessels into extravascular
compartment  decreased blood volume 
reduced renal perfusion  activation of renin-
angiotensin aldosterone system  increased
aldosterone and ADH secretion  increased renal
retention of Na+ and H2O  Edema.

48. Hepatic edema (Cirrhosis of liver):
– Hypoalbuminaemia- Diffuse hepatocellular damage
impairs the capacity of the liver to synthesize albumin and
thereby reducing the colloidal osmotic pressure.
– Portal hypertension- Increases hydrostatic pressure.
Development of portal hypertension due to extensive
fibrous scaring and distortion of intrahepatic vasculature.
– Secondary hyperaldosteronism- Less inactivation of
aldosterone by liver leading to secondary
hyperaldosteronism and retention of Sodium and water.

49. Classification:
• On the basis of nature of
fluid
– Inflammatory-
Exudative,
Rich in protein and
Specific gravity is 1.020.
– Non-inflammatory-
Transudative,
Low protein and
Specific gravity is 1.012.
• On the basis of site-
– Localized edema-
• Inflammatory edema.
• Hypersensitivity edema.
• Edema of venous obstruction.
• Lymphatic edema.
– Generalized edema (Anasarca)-
• Cardiac edema.
• Renal edema.
• Hepatic edema.
• Nutritional edema.
• Edema due to adrenal
hormones.

50. Classification:
Classification
by the extent
1、Anasarca : cardiogenic edema,
nephrogenic edema, etc.
2、Local edema : brain edema,
3、Hydrops--- A large amount of
fluid accumulates in the body cavities.
pulmonary edema etc.
ascites etc.

51. • Two types :
–Non inflammatory
- Increased hydrostatic pressure
- Decreased plasma osmotic pressure
- Lymphatic obstruction.
–Inflammatory
- During the process of inflammation.

52. Difference between Exudates and Transudate:

53. Clinical types
• Pitting edema
• Non pitting edema

54. Edema which forms Pit
When pressed is Pitting
Edema
Non Pitting edema

55. Grading scale of Edema

56. Pathophysiologic Causes of Edema

57. HEMORRHAGE

58. HEMORRHAGE
• Hemorrhage is extravasation of blood from
vessels into the extravascular space.
• Rupture of a large artery or vein results in severe
hemorrhage, and is almost always due to vascular
injury, including trauma, atherosclerosis, or
inflammatory or neoplastic erosion of the vessel
wall.

59. • Hemorrhage can be external or can be confined
within a tissue; any accumulation is referred to as a
Hematoma.
• Hematomas can be relatively insignificant (e.g., a
bruise) or can involve so much bleeding as to cause
death (e.g. a massive subarachnoid hematoma
resulting death.)

60. Types of Hemorrhage
• Petechiae.
• Purpura
• Ecchymoses.

61. Petechiae
• Minute (1- to 2-mm) hemorrhages mostly due to
broken capillary blood vessels into skin, mucous
membranes, or serosal surfaces are called
Petechiae.
• Are typically associated with
– locally increased intravascular pressure,
– low platelet counts (thrombocytopenia),
– defective platelet function, or
– clotting factor deficiencies.

62. Purpura
• Slightly larger (3- to 5-mm) hemorrhages are
called Purpura
– Associated with many of the same disorders that
cause petechiae; in addition, purpura can occur
with trauma, vascular inflammation (vasculitis)

64. Ecchymoses.
• Larger (1- to 2-cm) subcutaneous hematomas
(bruises) are called Ecchymoses.
– Extravasated red cells are phagocytosed and
degraded by macrophages.
– Characteristic color changes of a bruise are due to
the enzymatic conversion of hemoglobin (red-blue
color) to bilirubin (blue-green color) and eventually
hemosiderin (golden-brown).

66. • Large accumulations of blood in one or another of the body
cavities are called hemothorax, hemopericardium,
hemoperitoneum, or hemarthrosis.
• Patients with extensive hemorrhages occasionally develop
jaundice from the massive breakdown of red blood cells and
systemic increases in bilirubin.

67. Clinical Significance
• Depends on the volume and rate of blood loss.
• Rapid removal of around 20% of blood volume or slow losses of even
larger amounts may have little impact in healthy adults;
• Greater losses, however, can cause hypovolemic shock.
• The site of hemorrhage is also important; bleeding that would be trivial in
the subcutaneous tissues, may cause death if located in the brain.
• Finally, chronic or recurrent external blood loss (e.g., a peptic ulcer or
menstrual bleeding) causes a net loss of iron, leading to iron deficiency
anemia.
• In contrast, when red cells are retained (e.g., with hemorrhage into body
cavities or tissues), the iron can be reutilized for hemoglobin synthesis.

68. A: Petechial hemorrhages of the colonic mucosa, a
consequence of thrombocytopenia.
B: Fatal intracerebral hemorrhage.

69. HEMOSTASIS AND THROMBOSIS
• Hemostasis is the arrest of bleeding in small blood vessels
under normal physiological condition.
• Normal hemostasis is the result of a set of well-regulated
processes that accomplish two important functions
– Fluidity of blood is maintained within the blood vessels.
– Induce a rapid and localized hemostatic plug at a site of vascular injury.

70. • Process of hemostasis-
– Transient reflex neurogenic arteriolar vasoconstriction occurs,
augmented by endothelin.
– In primary hemostasis, exposed subendothelial extracellular matrix
allows platelet adhesion and activation. Secreted products recruit
other platelets to form a temporary hemostatic plug.
– In secondary hemostasis, injury also exposes tissue factor (factor III or
thromboplastin). Tissue factor activates the coagulation cascade,
resulting in thrombin generation and conversion of circulating
fibrinogen to insoluble fibrin. Thrombin induces further platelet
recruitment.
– Polymerized fibrin and platelet aggregates to form a solid permanent
plug.

71. • Contributors of hemostasis and thrombosis:
– Vascular wall specially Endothelium and underlying
subendothelial connective tissue.
– Platelet is essential for both hemostasis and
thrombus formation.
– Coagulation system.

74. (i) Endothelium
– Endothelial cells are central regulators of hemostasis.
– Normal endothelial cells express a variety of anticoagulant
factors that inhibit platelet aggregation and coagulation and
promote fibrinolysis; after injury or activation.
– Endothelium may be activated by infectious agents,
hemodynamic factors, plasma mediators, and, most
significantly, cytokines.

75. • It has two roles- Antithrombotic properties and Prothrombotic
properties.
• Antithrombotic action:
– Anti platelet effect- An intact endothelium prevents platelets and
plasma coagulation factors from meeting subendothelial ECM. It
inhibits platelet aggregation by liberation of PGI2, NO, ADPase. They
are also potent vasodilator.
– Anticoagulant effect- Mediated by heparin like molecule and
thrombomodulin-
• Releases heparin like molecule, which accelerates antithrombin-III.
Antithrombin-III inactivates thrombin, factor-Xa, and other clotting factors.
• Releases thrombomodulin, which accelerate the function of protein-C
and protein-S. Protein-C splits factors Va and VIIIa.
• Tissue factor pathway inhibitor (TFPI)- It complexes and inhibits
activated tissue factor-factor VIIa and factor Xa molecule.
– Fibrinolytic effects- Tissue plasminogen activator (t-PA)-
It promotes fibrinolytic activity to clear fibrin deposits from
endothelial surfaces.

76. • Prothrombotic action:
– Platelet effect- Stimulation of platelet aggregation and
adhesion by von-Willebrand’s factor and platelet
activating factor.
– Procoagulant effect- Endothelial cells synthesize tissue
factor, which activates the extrinsic coagulation cascade.
– Antifibrinolytic effects- Secretes t-PA inhibitor, which
depresses fibrinolysis.

78. (ii) Platelet:
– Platelets play a central role in normal hemostasis
and thrombosis.
– When circulating, they are expressing a number
of glycoprotein receptors on their surfaces.
– After vascular injury, platelets encounter
subendothelial extracellular matrix. This initiates
the sequences of platelet activation-

79. Sequences of platelet activation-
1. Platelet adhesion- Adhesion refers to
attachment of platelets to sites of endothelial
cell injury, where subendothelial elements are
exposed.
– It is mediated by von-Willebrand’s factor, which acts as a
bridge between platelet surface receptors and exposed collagen.
2. Secretion- Secretion of the contents of the platelet
granules occurs soon after adhesion.
• It has α-granules and dense body.

80. • α-granules- Express P-selectin on their membrane and
contain-
• Fibrinogen.
• Fibronectin.
• Factor-V & VIII.
• Platelet factor-4.
• Transforming growth factor-b.
• Platelet derived growth factor (PDGF).
• Dense body ( granules)-
– Ca++.
– ADP, ATP.
– Histamine.
– Seretonin.
– Epinephrine.

81. 3. Platelet aggregation-
• It is promoted by ADP and thromboxane-A2.
• Platelet aggregation creates the primary hemostatic
plug.
• Activation of coagulation cascade generates thrombin
and fibrin, which act to form an irreversibly fused
mass of platelets and fibrin, constituting the definitive
secondary hemostatic plug.

82. (iii) Coagulation cascade-
– The coagulation cascade is essentially a series of
enzymatic conversions, turning inactive proenzymes
into activated enzymes and ultimately formation of
thrombin.
– Thrombin then converts the fibrinogen into fibrin.

85. Regulation of coagulation
• Clotting is regulated by four types of natural anticoagulants-
– Antithrombins- They inhibit the activity of thrombin and other
serin proteases- factors IXa, Xa, XIa and XIIa.
– Protein C & S- They are able to inactivate factors Va and VIIIa.
– Tissue factor pathway inhibitor (TFPI)- A protein secreted by
endothelium , complexes to factor Xa and tissue factor-VIIa
and inactivates them rapidly to limit coagulation.
– Fibrinolytic system- They limit the size of the final clot.

86. • Fibrinolytic system
– This is primarily accomplished by the generation of plasmin.
– Plasmin is derived from its inactive circulating precursor plasminogen,
either by a factor-XII-dependent pathway or by two distinct types of
plasminogen activators.
– Plasmin breaks down fibrin and interferes with its polymerization.
– The resulting fibrin split products (FSP) also act as weak
anticoagulants.
– Elevated levels of FSP found in DIC, deep venous thrombosis or
pulmonary thromboembolism.

88. THROMBOSIS
• It is the formation of a clotted mass within non-
interrupted vascular system by constituents of
blood.
• Thrombosis refers to an inappropriate activation of
normal hemostatic processes, such as the
formation of blood clot (thrombus) in uninjured
vasculature or thrombotic occlusion of a vessel
after relatively minor injury.

89. Thrombogenesis
• Three factors can predispose to thrombus
formation (Virchow’s triad).
– Endothelial injury- Can only form thrombus.
– Alterations of normal blood flow.
– Blood hypercoagulability.

90. Virchow's triad

91. Pathogenesis
Endothelial injury
(i) Endothelial injury-
– It is the dominant influence and by it self can
leads to thrombosis.
– It may occur in the form of :
• Physical loss of endothelium or
• Endothelial dysfunction.

92. • Physical loss of endothelium leads to exposure of
subendothelial ECM, adhesion of platelets, release of tissue
factor, and local depletion of PGI2 and PA.
• Causes :
– Thrombi in the cardiac chambers after myocardial
infarction,
– Ulcerated plaques in atherosclerotic arteries,
– At sites of traumatic or inflammatory vascular injury
(vasculitis).

93. • Dysfunctional endothelium may elaborate greater amount
of procoagulant ( e.g., platelet adhesion molecules, tissue
factor, PAI) or may synthesize less anticoagulant effectors
(e.g., thrombomodulin, PGI2, t-PA).
• Causes :
– Hypertension,
– Turbulent blood flow,
– Bacterial products,
– Radiation injury

94. • Site- Heart, large size arteries
• Of note, endothelium need not be denuded or
physically disrupted to contribute to the development
of thrombosis; any imbalance between prothrombotic
and antithrombotic activities of endothelium can
influence local clotting events.

95. Pathogenesis
Alteration of blood flow
(ii) Alteration of blood flow-
• Normal blood flow is laminar. It is disturbed by turbulence or stasis.
– Turbulence- Turbulence contributes to Arterial and cardiac
thrombosis by causing endothelial injury or dysfunction as well as
forming countercurrent and local pocket of stasis.
• Example- rupture of atheromatous plaque in blood vessels,
aneurysmal dilation of blood vessels.
– Stasis (Sluggish blood flow)- Stasis is a major factor in the
development of venous thrombi. Example- Polycythemia, sickle cell
anemia.

96. Effects of turbulence and stasis
– Disrupt of laminar blood flow and bring platelets
into contact with endothelium.
– Prevent dilution of the activated clotting factors
by the fresh flowing blood.
– Retard the inflow of clotting inhibitors and permit
buildup of thrombi.
– Promote endothelial cell activation, predisposing
to local thrombosis, leucocyte adhesion, and a
variety of other endothelial cell effects.

98. Pathogenesis
Hypercoagulability
• Defined as any alteration of the coagulation
pathways that predisposes to thrombosis.
• Hypercoagulability contributes infrequently to
arterial or intracardiac thrombosis but is an
important underlying risk factor for venous
thrombosis.
• Can be divided into Primary (genetic) and
Secondary (acquired) disorders

99. • Primary (inherited) hypercoagulability most often is caused by
mutations in the factor V and prothrombin genes:
– Factor V mutation (called the Leiden mutation) alters an amino acid
residue in factor V and renders it resistant to protein C. Thus, an
important antithrombotic counter-regulatory mechanism is lost.
– Mutation of prothrombin genes results in increased prothrombin
transcription causes elevated plasma prothrombin levels
(hyperprothrombinemia) and threefold increased risk for venous
thrombosis.
– Less common primary hypercoagulable states include inherited
deficiencies of anticoagulants such as antithrombin III, protein C, or
protein S.

100. • Secondary (acquired) hypercoagulability is seen in many
clinical condition.
– In some situations (e.g., cardiac failure or trauma), stasis
or vascular injury may be the most important factor.
– Oral contraceptive use and the hyperestrogenic state of
pregnancy, increased hepatic synthesis of coagulation
factors and reduced synthesis of antithrombin III.
– In disseminated cancers, release of procoagulant tumor
products (e.g., mucin from adenocarcinoma) predisposes
to thrombosis.

101. – The hypercoagulability seen with advancing age has
been attributed to increased platelet aggregation and
reduced release of PGI2 from endothelium.
– Smoking and obesity promote hypercoagulability by
unknown mechanisms.
– Following major surgery or trauma
– In pregnancy and parturition
– After splenectomy
– Prolonged immobility
– Sickle cell disease
– Antiphospholipid syndrome

102. Hypercoagulable States

103. Morphology of Thrombus formation:
• Thrombi may develop anywhere in the cardiovascular
system.
• They are of variable size and shape, depending on the site
of origin and the circumstances leading to their development.
• Arterial thrombi usually begin at a site of endothelial injury or
turbulence.
• Venous thrombi characteristically occur in sites of stasis.
• Thrombi are focally attached to the underlying vascular surface.

104. Classification of thrombus
• Arterial thrombi tend to grow in a retrograde direction
from the point of attachment. They typically arise at sites
of endothelial injury or turbulence
• Venous thrombi extend in the direction of blood flow
(thus both tend to propagate toward the heart). They
characteristically occur at sites of stasis
• The propagating portion of a thrombus is poorly
attached and therefore prone to fragmentation,
generating an Embolus.

105. Classification of thrombus
Based on color
– Pale thrombus- Composed of platelets with small amount of
fibrin. Generally formed in heart and arteries due to rapid
circulation.
– Red thrombus- Due to trapped RBC largely because of
thrombus formation in a relatively static environment.
– Mixed thrombus- Composed of both platelet and red cells. In the
mixed thrombus- lines of Zahn is formed.

106. Classification of thrombus
• Lines of Zahn- When thrombi are formed within a
cardiac chamber or aorta, they may have apparent
lamination called Lines of Zahn.
– They are usually seen in capacious blood vessels.
– Pale areas are composed of platelet and fibrin.
– Darken area containing more red cells.
– Venus side- Line of Zahn rare.

107. lines of Zahn
alternating pale pink bands of platelets with fibrin and red bands of RBC's
forming a true thrombus.

108. Line of zahn

109. Classification of thrombus
• Such lines are only found in thrombi that form in flowing
blood.
• Their presence can therefore usually distinguish
antemortem thrombosis from the nonlaminated clots that
form in the postmortem thrombosis .
• Although thrombi formed in the “low-flow” venous system
superficially resemble postmortem clots, careful evaluation
generally reveals ill-defined laminations.

110. Classification of thrombus
1. Based on site and mode of formation
– Mural thrombus.
– Occlusive thrombus.
– Vegetations.
– Propagating thrombus.
– Pedunculated thrombus.
– Ball thrombus - formed in the left atrium.
– Laminated thrombus.

111. Valve thrombus is called
Vegetations Mostly
Occur in Mitral valve

112. 2. Based on infection-
– Bland or aseptic thrombus.
– Septic or infected thrombus.

113. Based on occlusion: -
It varies from site to site:-
– Mural thrombus- It is attached to a wall but does not completely
occludes the lumen of the vessel.
• It occurs in the capacious lumen of the heart chamber and
aorta, sometimes in the coronary, iliac and common carotid
arteries.
• Causes of mural thrombus formation-Myocardial infarction (Lt
ventricle); Infective endocarditis; Rheumatic heart disease;
SLE.
– Occlusive thrombus- A thrombus that completely occludes the
lumen of the vessels. Small artery, vein and capillary.
• Site of – iliac, common carotid, coronary, cerebral and femoral
blood vessels.
• Vein- Calf vein, popliteal, femoral, sometimes iliac vein.

115. Occlusive artery
Completely occluding
The blood vessels

117. 4. Based on duration-
– Recent or fresh thrombus.
– Healed thrombus- Organized, calcified or
ossified thrombus.

118. Fate of the Thrombus
• Propagation: accumulation of additional
platelets and fibrin, eventually causing vessel
obstruction.
• Embolization: Thrombi dislodge or fragment
and are transported elsewhere in the
vasculature.
• Dissolution: Thrombi are removed by
fibrinolytic activity.

119. • Organization and recanalization:
– Older thrombi become organized by the in growth
of endothelial cells, smooth muscle cells, and
fibroblasts into the fibrin-rich thrombus.
– In time, capillary channels are formed that- to a limited
extent- create channel along the length of the thrombus,
thereby reestablishing the continuity of the original lumen.

120. Fate of thrombosis

121. Venous Thrombosis
• There are two types of venous thrombosis -
–Thrombophlebitis - in which the vein wall
is inflamed.
–Phlebothrombosis - which is due to stasis
of blood in uninflammed vein.

122. Phlebothrombosis
• It occurs in uninflammed vein and almost invariably
occlusive.
• Most commonly affected the vein of lower
extremity (90%), such as deep calf, popliteal,
femoral and iliac vein.
• Less commonly may develop in periprostatic
plexus, ovarian or periuterine veins.

123. Venous Thrombosis
(Phlebothrombosis)
• Venous thrombi occur in either the superficial or the deep
veins of the leg.
• Superficial venous thrombi usually arise in the saphenous
system, particularly in the setting of varicosities.
– Rarely embolize.
– Can be painful.
– Cause local congestion and swelling from impaired venous
outflow, predisposing the overlying skin to development of
infections and varicose ulcers.

126. • Deep venous thromboses (“DVTs”) in the larger leg
veins at or above the knee joint (e.g., popliteal, femoral, and
iliac veins).
– More serious because they are prone to embolize.
– DVTs may cause local pain and edema.
– The venous obstruction often is circumvented by
collateral channels. Consequently, DVTs are entirely
asymptomatic in approximately 50% of patients.

127. Deep venous Thrombosis
• Clinical conditions associated with deep venous
thrombosis-
– Advanced age, prolonged bed rest or immobilization.
– Congestive cardiac failure.
– Trauma, surgery and burns.
– Pregnancy and postpartum states.
– Tumor associated procoagulant release.

128. Deep Vein Thrombosis
Causes
• Changes in vessel wall- Compression by heavy calf muscles, local hypoxia
and direct trauma etc.
– Changes in blood flow- Stasis is the most important factor. The causes
of venous stasis may be classified as follows-
• General conditions-
– Reduced cardiac output- heart failure, shock.
– Impaired venous return.
• Local causes-
– Lack of muscular activity.
– Incompetent valves.
– Pressure from out side.
– Changes in the composition of the blood.

129. Complications
– Massive pulmonary embolism.
– Smaller pulmonary emboli, with or without
pulmonary infarction.
– Pulmonary hypertension.

130. EMBOLISM

131. EMBOLISM
• An embolus is an intravascular solid, liquid, or
gaseous mass that is carried by the blood to a
site distant from its point of origin.
Sources of embolus formation / Cause :
– Embolus is formed by thrombus in 99% cases. So, it
is called thromboembolism.
– Rare cases- Bone, bone marrow, fat, air, tumor,
amniotic fluid, parasite.
• Thrombus occurs in site of origin. Embolism occurs distant to
origin.

132. Types of Embolism
• Thromboembolism.
• Gas embolism—air, nitrogen.
• Fat.
• Tumor fragments.
• Miscellaneous -
• Foreign bodies.
• Parasites- schistosomal ova.
• Red cell aggregates.
• Amniotic fluid.
• Fragment of bone.
• Atheromatous debris from ruptured atheromatous plaque.

133. Thromboembolism
• Pulmonary thromboembolism - If it
originates from venous end.
• Systemic thromboembolism - If it
originates from arterial end.

134. Pulmonary thromboembolism
• Occlusion of pulmonary arteries are almost always embolic;
in situ thromboses are rare, occurring only with pulmonary
hypertension and pulmonary atherosclerosis.
• In 95% cases occlusion occur by embolus and 5% cases
occlusion occur by thrombus.
• Greater than 95% of pulmonary emboli arise in deep veins of
legs.
• Source -
– Popliteal, femoral, iliac (common).
– Superficial vein of lower extremity (rare).
– Calf vein.
– Ovarian, periprostatic, periuterine vein.

135. Effects of pulmonary embolism
• These depends on-
– Size of emboli (small, medium and large).
– Site of location of embolus.
– Number of emboli.
– The proportion of entire arterial tree obstructed.
– The underlying cardiorespiratory status of the
patient.
– Release of vasoactive factor TXA2 from platelet.

136. Consequences of Pulmonary Embolism
• Potential consequences are-
– Large emboli (about 5%)- It may impact across
the bifurcation of pulmonary artery producing
saddle embolism or it may occlude the main
pulmonary artery (60% or more), there will be
• Sudden death.
• Acute Right heart failure.
• Cardiovascular collapse.

137. Consequences of Pulmonary Embolism
– Middle sized emboli (about 20-35%)- they occlude
moderate sized peripheral pulmonary branches-
• May induce pulmonary hemorrhage.
• Infarction due to Left heart failure.
– Small emboli (60-80%)-
• Clinically silent.
• May cause hemoptysis due to pulmonary hemorrhage.

138. Fate of Pulmonary Embolism
• Complete resolution.
• If embolism occludes small end arteriolar
pulmonary branches (10-15%), there will be
pulmonary infarction.
• Embolus occlude medium size blood vessel (10-
15%), there will be hemoptysis due to
Hemorrhage in the lung.
• Sometimes, blood vessels occluded by small
emboli, ultimately there will be organization,
thickening of blood vessel decreased elasticity
increased pulmonary hypertension.

139. Different names given
• Paradoxical embolism - When an embolus
may pass through an interatrial or
interventricular defect to gain access to the
systemic circulation.
• Saddle embolus - Depending on the size of
the embolus, it may occlude the main
pulmonary artery, impact across the
bifurcation.

140. Saddle embolism in
Pulmonary artery branch

142. Systemic thromboembolism
• Systemic thromboembolism refers to emboli
traveling within the arterial circulation.
• Source (mainly) = thrombus.

143. Source / formation
• Heart (80-85%)- mural thrombus -
– Cause
• Myocardial infarction (Left ventricle) - 60-65%.
• Rheumatic heart disease (Left atrium)- 5-10%.
• Cardiomyopathy - 5%.
• Atrial fibrillation.
• Infective endocarditis.
• Aorta -
– Cause
• Aortic aneurysm.
• Rupture of atheromatous plaque.
• Idiopathic - 10%.

144. Termination of Embolus
• Inferior extremity (70-75%)- there will be formation of
• Gangrene.
• Ischemia in lower extremity.
• Brain (10%) - It occludes middle cerebral artery cause
cerebral infarction. Death may occur within 24 hours.
• Abdominal viscera (10%) liver, kidney, intestine, there will be
simple infarction without any effect.
• Superior extremity (5-10%) embolus causes-
• Simple infarction.
• Without effect.

145. Amniotic Fluid Embolism
• Amniotic fluid embolism is a serious but
uncommon complication of labour and the
immediate postpartum period.
• Sign- Sudden severe respiratory distress; Cyanosis;
Hypotensive shock; Seizures; Coma.
• Pathogenesis-
– The underlying cause is the infusion of amniotic
fluid with all of its contents into the maternal
circulation following tear in the placental
membranes and rupture of uterine or cervical
veins.

146. Amniotic fluid embolism

147. AIR EMBOLISM
• Gas bubbles within the circulation obstruct vascular flow
and damage tissues just as certainly as thrombotic
masses (Barotrauma).
• Generally, in excess of 100 cc air is required to have a
clinical effect.
• The bubbles act like physical obstructions and may
coalesce to form frothy masses sufficiently large to
occlude major vessels.

149. AIR EMBOLISM
• Cause-
– During delivery due to rupture of uterine blood
vessels following uterine contraction.
– During the performance of a pneumothorax
when a large artery or vein is ruptures or entered
accidentally.
– When injury to the lung or the chest wall opens a
large vein and permits the entrance of air during
the negative pressure phase of inspiration.

150. AIR EMBOLISM
• Decompression sickness
– A special form of air embolism occurs when individuals
are exposed to sudden changes in atmospheric pressure.
– It occurs in scuba and deep-sea divers, under water
construction workers, in rapid ascent.
– When air breathed at high pressure, increased amount of
gas (particularly Nitrogen, helium) becomes dissolved in
the blood and tissues. O2 is rapidly soluble in water. N2
and He are not soluble rapidly. If the person
depressurizes too rapidly, the nitrogen expands in the
tissues and bubbles out of solution in the blood to form
gas emboli.

151. • Acute form of decompression sickness
– The acute form is known as bends or chokes.
• When air enters into blood vessel around joint and
skeletal muscle causes pain. They may produce
acute respiratory distress.

152. • Chronic form of decompression sickness
– It is known as Caisson disease.
– Persistence of gas emboli in the skeletal system
leads to multiple foci of ischemic necrosis.
• The more common sites are the heads of the
femurs, tibia and humerus.

153. Fat Embolism
• Soft tissue crush injury or rupture of marrow vascular
sinusoids (long bone fracture) releases microscopic fat
globules into the circulation.
Causes:
• Traumatic causes-
– Fracture of large bone such as femur and pelvis (90%).
– Extensive soft tissue trauma.
– Burn.
• Non-traumatic causes-
– Pancreatitis.

154. Fat embolism syndrome
• No clinical manifestation, only 10% manifest this
syndrome.
• Clinical manifestation- appear 1 to 3 days after injury
• Pulmonary insufficiency.
• Neurological manifestation (coma, restless
ness).
• Anemia- Consequence of erythrocyte
aggregation and hemolysis.
• Thrombocytopenia- Caused by platelet
adhering to the fat globules and being removed
from the circulation.

155. INFARCTION

156. INFARCTION
• It may be defined as an area of ischemic necrosis caused by
occlusion of either the arterial supply or the venous drainage
in a particular tissue.
• Cause-
– Mainly by arterial thrombus or embolus. (99% cases).
• Other uncommon cause-
– Local vasospasm.
– Narrowing by atheromatous plaque.
– Extrinsic compression of a vessel (e.g., by tumor)
– Twisting of blood vessel.
– Compression of the blood supply by edema
– Traumatic rupture of the blood vessel.

157. Type of infarction
• Depending on colour-
– White infarct
– Red infarct.
• Depend on the presence or absence of
bacteria-
– Septic.
– Aseptic.

158. • White infarction occurs with arterial occlusion in solid organs
(heart, spleen and kidney) with end arterial circulation.
• Red infarction occurs-
– Loose organ (Lung).
– Venous occlusion.
– Double blood supply (Lung).
– When flow is reestablished to a site of previous arterial
occlusion and necrosis.

159. Morphology of infarction
• Macroscopic-
• Wedge-
– Apex toward the blood vessels and base away from blood vessel.
– The lateral margins may be irregular reflecting the pattern of vascular supply
from adjacent vessels.
• At the outset - All infarcts are poorly defined and slightly hemorrhagic.
• The margins of both types of infarcts tend to become better defined with
time by inflammation at the edge of the lesion.
• Within few days - White yellow white.
Red no such change.
• Consistency is firm in both cases.

160. Figure: Red and white infarcts. A, Hemorrhagic, roughly wedge-shaped
pulmonary infarct (redinfarct). B, Sharply demarcated pale infarct in the spleen
(white infarct).

161. Morphology of infarction
Microscopic
• All infarction are coagulative necrosis except brain.
• An initial inflammatory response (lasting hours to
days) is followed by a reparative response beginning
in the preserved margins.
• In stable or labile tissues, some parenchymal
regeneration may occur where the underlying stromal
architecture is spared.
• Most infarcts are ultimately replaced by scar tissue.

163. • Factors that influence development of an infarct-
– Nature of the vascular supply- The availability of an alternative
blood supply is the most important factor in determining the extent of
damage.
– Rate of development of the occlusion- Slowly developing
occlusions are less likely to cause infarction because they provide
time for the development of alternative perfusion pathway.
– Vulnerability of a given tissue to hypoxia- The susceptibility of a
tissue to hypoxia influences the likelihood of infarction.
– Oxygen content of blood- The partial pressure of oxygen in blood
also determines the outcome of vascular occlusion.

164. Disseminated Intravascular
Coagulation (DIC)

165. Disseminated Intravascular
Coagulation (DIC)
• DIC is an acute, subacute or chronic thrombo-hemorrhagic
disorder occurring as a secondary complication of any
condition associated with widespread activation of thrombin.
• It is characterized by activation of the coagulation sequence,
leading to the formation of microthrombi throughout the
microcirculation.
• As a consequence of the thrombotic diathesis, there is
consumption of platelets, fibrin, and coagulation factors and,
secondarily, activation of fibrinolytic mechanisms
(Consumption coagulopathy).

166. Clinical situation in which DIC
associated:
• Obstetrical cause - (50%)
– Abruptio placenta.
– Retained dead fetus.
– Amniotic fluid embolism.
• Infective cause -
– Gram-negative sepsis.
– Meningococcaemia.
– Malaria.
• Neoplasms - (30 –33%)
– Carcinoma of pancreas, lung
and stomach.
– Acute promyelocytic
leukemia.
• Massive tissue injury -
– Traumatic.
– Burns.
– Extensive surgery.
• Miscellaneous -
– Acute intravascular
hemolysis.
– Snake bite.

167. Pathogenesis of DIC
• Over activation of Tissue Factor.
• Over activation of factor XII
• Decrease Fibrinolytic activity.
• Decrease anticoagulative property ( Protein
C etc.)

168. Pathogenesis:
• Release of tissue factor (extrinsic pathway) -
– Obstetric case
• Gram-negative septicemia endothelial injury tissue factor release.
• Placenta in obstetric complication.
– Malignancy- Granules of leukemic cells, mucus released
from certain adenocarcinoma.
– Tissue injury.

169. • Wide spread endothelial injury (Intrinsic pathway
and extrinsic pathway will be activated)-
– Endothelial injury can initiate DIC by causing
release of tissue factor from endothelial cells and
by promoting platelet aggregation.
– Also activate the intrinsic pathway as a result of
exposure of subendothelial connective tissue.
• Wide spread endothelial injury may be produced by-
– SLE- antigen-antibody complex.
– Burn injury
– Microorganism- Meningococci

171. Typical clinical manifestation of DIC
– Bleeding
– Shock
– MOF (MODS)
– Hemolytic Anemia.

172. • Basic lesion -
– Thrombus produce infarction - in different organs
like Brain, liver, lung, kidney, adrenal gland and
sometime pituitary gland (Sheehan’s syndrome).
– Bleeding.

173. Shock

174. Shock
• Shock is defined as a state of systemic tissue
hypoperfusion due to reduced cardiac output
and/or reduced effective circulating blood
volume.

175. Classification
• Cardiogenic-
– Myocardial infarction.
– Arrhythmias.
– Cardiac tamponade.
– Pulmonary embolism.
• Hypovolemic-
– Hemorrhage.
– Fluid loss-from vomiting
and diarrhea.
• Septic-
– Endotoxic shock.
– Gram positive septicemia
– Overwhelming bacterial infections.
• Neurogenic
– Anesthesia.
– Spinal cord injury.
• Anaphylactic shock.

176. Cardiogenic shock:
• Principal mechanism - Failure of myocardial pump
due to intrinsic myocardial damage/extrinsic
pressure or obstruction to outflow.
• Causes -
» Myocardial infarction.
» Arrhythmias.
» Cardiac tamponade.
» Massive pulmonary embolism out flow obstruction Left
heart failure shock.

177. Hypovolemic shock
• Principal mechanism - Decreased cardiac output due to
inadequate blood or plasma volume.
• Causes:
• Hypovolemia may be due to hemorrhagic or non-
hemorrhagic causes.
Non-hemorrhagic causes include :
1. Poor fluid intake (dehydration) and
2. Excessive fluid loss because of vomiting, diarrhea, urinary
loss (e.g. diabetes),

178. Septic shock
• Principal mechanism- Peripheral vasodilation and pooling
of blood endothelial activation / injury, leucocyte induced
damage, DIC.
• Causes-
– Overwhelming bacterial infection- due to gram negative
septicemia (endotoxic shock).
– In few cases, gram positive septicemia, occasionally fungi.

179. Neurogenic shock
– Principal mechanism- Loss of vascular tone
and peripheral pooling of blood.
• Cause-
– Spinal cord injury.
– Anesthetic accident.

180. Anaphylactic shock
• It is due to Type-1 hypersensitivity reaction.
• Principal mechanism- caused by an immune-mediated
reaction in which vasodilator substances such as histamine
are released into the blood.
– These substances cause dilatation of arterioles and venules along
with a marked increase in capillary permeability.
– Anaphylactic shock is often accompanied by bronchospasm, heart
muscle depression.
• Cause :
– Anaphylaxis can occur in response to almost any foreign substances
include venom from insect bites or stings, foods, and medication.

181. Stages of shock
• Shock is a progressive disorder. If it is uncorrected
patient will die.
• Unless the insult is massive and rapidly fatal, shock
tends to evolve through three general phases.
• Shock will progress-
– Non-progressive stage.
– Progressive stage.
– Irreversible stage.

182. （1） Ischemic hypoxia stage
(Early stage of shock or Compensated stage)
（2） Stage of stagnant hypoxia
(Stage of shock or Decompensated stage)
(3) Stage of microcirculatory failure
(Late stage of shock or Refractory stage of shock or Irreversible stage)
Develops
Develops

183. Non-progressive stage:
• During which reflex compensatory mechanisms are activated and
perfusion of the vital organs are maintained.
• Condition-
– Mild hemorrhage.
– Mild trauma.
• In non-progressive shock, a variety of neurohormonal mechanisms help
to maintain CO and BP. These mechanisms are-
– Baroreceptor mechanism reflex.
– Release of catecholamines.
– Activation of renin angiotensin axis.
– Release of ADH.
– Generalized sympathetic stimulation.

184. Progressive stage
Less perfusion of vital organ.

Less O2 and nutrition supply.

Shifting of aerobic glycolysis to anaerobic glycolysis.

Increased lactic acid formation.

Lactic acidosis.

 pH and this cause withdrawal of sympathetic stimulation.

Vasodilation (Dilation of arteriole).

Pooling of blood to periphery.

Decrease central blood volume.

CO

blood flow is slow down, which is caused by RBC aggregation, WBC rolling and platelet
aggregation and adhesion

The inflow > outflow from capillary, leading to blood stasis and tissue hypoxia

185. Irreversible stage
• In irreversible stage cellular and tissue injury so severe
that even if the hemodynamic defects are corrected,
survival is not possible.
Blood stasis

Endothelial injury

DIC

MOF

186. – Leakage of lysosomal enzymes leading wide spread
cell injury.
– Myocardial dysfunction due to increased nitric oxide
synthesis.
– Entrance of intestinal flora leading to endotoxic shock.
– Renal shutdown due to acute tubular necrosis.

187. Morphology of shock
• Since shock is characterized by failure of multiple organ
system, the cellular changes may appear any tissue.
– Brain- Ischemic encephalopathy.
– Heart- Sub-endocardial hemorrhage and / or necrosis.
– Lung- Diffuse alveolar damage in septic shock.
– Kidney- Acute tubular necrosis.
– Adrenal gland- Depletion of fat due to excess synthesis of
catecholamines and necrosis occurs at cortical region.
– GIT- Hemorrhagic enteropathy.

188. Pale face
Pale, cold and
clammy
skin→cyanotic
Dysphoria →
Apathy or coma
rapid pulse
→weakened
pulse
BP(-)→BP↓
oliguria→anuria
Causes
Clinical Manifestations
early stage
serious stage

189. THE END