DR. MYM pathology for PHO unit 7(5).pdf

Hemodynamic Disorders
Samara University
Department of Biomedical Sciences
6/21/2022 1
Chapter 7: Hemodynamic disorder
DR. MYM
Dr. Mohammed. Y (MD, Lecture)

Objectives
❑ At the end of this session the student will be able to:
✓ Describe fluid balance is maintained in the circulation
✓ Define Hemorrhage
✓ Elaborate the Pathogenesis & causes of myocardial infarction,
Thrombosis, Embolism, DVT,PTE, DIC
✓ Know Pathology of fluid balance disruption
✓ Basic knowledge about types of shock, pathogenesis, &
complications
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Introduction:
✓ Well being of cells & tissues depend not only on an intact
circulation but also on normal fluid homeostasis.
❖ Homeostasis, the maintenance of a stable equilibrium, especially
through physiological processes.
✓ The major causes of morbidity and mortality in developed
countries are associated, with failure to maintain normal fluid status.
✓ Normal fluid homeostasis requires:-
✓ Vessel wall integrity
✓ Maintenance of intravascular pressure and osmolality.
✓ we focus on disorders of hemodynamics (edema, congestion, and
shock) and hemostasis (hemorrhage and thrombosis), as well as
various forms of embolism.
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Body Fluids
❖ Total body fluid is distributed mainly between two compartments:
1. Extracellular fluid and the
2. Intracellular fluid .
➢ The Extracellular fluid is divided into the interstitial fluid and
the blood plasma.
✓ Approximately 60% of lean body weight is water,
➢ 2/3 is intracellular and
➢ 1/3 is extracellular, mostly as interstitial fluid
➢ Only 5% of total body water is in blood plasma
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Body Fluids…..
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HEMODYNAMICS
➢ In a normal blood vessel like capillary, there are two forces
(Starling forces) acting on the fluid in the circulation.
I. The hydrostatic pressure causes fluid movement from inside
the vessel to outside and
II. Colloid osmotic pressure (mostly due to proteins) is
responsible for the reverse movement of fluid from outside the
vessel to the inside.
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✓ The capillary hydrostatic and osmotic forces are normally balanced
so that there is no net loss or gain of fluid across the capillary bed.
✓ ed hydrostatic pressure or diminished plasma osmotic pressure
leads to a net accumulation of extravascular fluid (edema).
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Edema
➢ In edema, the excessive interstitial or body cavities fluid can be
either an exudate or a transudate.
I. A transudate is a fluid with low protein content (albumin) and
a specific gravity of less than 1.012.
➢ It is essentially an ultrafiltrate of blood plasma that results from
osmotic or hydrostatic imbalance across the vessel wall
without an increase in vascular permeability.
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II. An exudate is an inflammatory extravascular fluid that has a
high protein concentration, cellular debris, and a specific
gravity above 1.020.
➢ It is formed mainly due to alteration in normal permeability
of small blood vessels in the area of injury.
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Edema Cont’d…
❑ Depending on the site of
accumulation:
✓ Hydrothorax:- pleural space
✓ Hydro pericardium
✓ Hydroperitoneum/ ascites
✓ Anasarca-generalized edema
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Mechanism of Edema Formation
➢ The capillary endothelium acts as a semipermeable membrane and
highly permeable to water & to almost all solutes in plasma with an
exception of proteins.
➢ Proteins in plasma and interstitial fluid are especially important
in controlling plasma & interstitial fluid volume.
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❑ Edema formation determined by:
1. Hydrostatic pressure
2. Oncotic pressure (colloid pressure)
3. Vascular permeability
4. Lymphatic channels
5. Sodium and water retention
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Mechanisms of Edema formation
❑ Four primary forces (starling forces) that determine fluid
movement across the capillary membrane are:
1. The Capillary hydrostatic pressure
2. The Interstitial hydrostatic pressure
3. The plasma oncotic pressure
4. The interstitial colloid pressure
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1. The capillary pressure (Pc), which tends to force fluid outward
through the capillary membrane.
2. The interstitial fluid pressure (Pif), which tends to force fluid
inward through the capillary membrane when Pif is positive but
outward when Pif is negative.
3. The capillary plasma colloid osmotic pressure (Πp), which
tends to cause osmosis of fluid inward through the capillary
membrane.
4. The interstitial fluid colloid osmotic pressure (Πif), which tends
to cause osmosis of fluid outward through the capillary membrane
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❑ Pathologic edema can be divided in to two broad categories:
A. Edema due to decreased plasma oncotic pressure
✓ E.g:- NS, Cirrhosis, malnutrition, protein losing enteropathy
B. Edema due to increased capillary pressure
✓ E.g:- DVT-Impaired venous return, Pulmonary edema,
cerebral edema, congestive heart failure
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Edema Cont’d…
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❑ Lymphatic obstruction
➢ Impaired lymphatic
drainage(blockage) and
consequent lymphedema
➢Usually localized &
inflammatory
e.g. Filariasis
(lymphangitis and fibrosis)
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Clinical Classification of Edema:
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Localized Generalized
DVT NS
Pulmonary edema Liver cirrhosis
Brain edema Malnutrition
Lymphatic Edema CHF
Renal failure
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Common site of Edema
✓ Subcutaneous tissue
✓ Lung
✓ Brain
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Subcutaneous edema
❑ Two patterns: Dependent & Diffuse
a) Dependent edema
✓Sites of increased hydrostatic pressure & influenced by gravity
➢ Leg and sacrum
✓ is a prominent feature of HF, particularly of the right ventricle.
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b) Diffuse
✓ Affects all parts of the body equally.
✓ Starts with periorbital edema
✓ E.g Renal dysfunction or nephrotic syndrome
➢ Pitting edema-
✓ Finger pressure over significantly edematous tissue displaces the
interstitial fluid and leaves a finger-shaped depression
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Morphology of subcutaneous Edema
Grossly – easily recognizable
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✓ Increased fluid in the alveolar spaces and interstitial of the lung
✓ Typically occurs in the setting of left ventricular failure,
pulmonary infections, adult respiratory distress syndrome
✓ Lungs weigh 2-3 times their normal weight
✓ Sectioning reveals frothy blood tinged fluid
Pulmonary edema
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Pulmonary edema cont…
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Edema of the Brain
❑ Localized vs generalized
1. Localized brain edema
✓ Sites of injury:- E.g:-
Trauma, abscess,
neoplasm
2. Generalized brain edema
✓ Encephalitis
✓ Hypertensive crisis
✓ Obstruction to brains
venous outflow
✓ Severe trauma
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Clinical significance of Edema
❑ Subcutaneous edema
✓ Signals underlying disease
✓ Impair wound healing
✓ Impair clearance of infection
❑ Pulmonary edema
✓ Interferes with normal ventilatory function → Death
✓ Fluid collect in the alveolar septa around capillaries →
impaired oxygen diffusion and enhanced bacterial infection.
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Hyperemia and Congestion
❑ Hyperemia and congestion indicate a local increased volume of
blood in a particular tissue
➢ Hyperemia
✓ is an active process resulting from augmented tissue inflow
because of arteriolar dilation.
✓ Occur in inflamed tissues and exercising muscle
✓ Tissues become red b/c of engorgement with oxygenated blood.
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❑ Congestion
➢ Passive process resulting from impaired outflow from a tissue
➢ It could be:- Systemic – Cardiac failure or Local:- DVT
➢ Congestion and edema commonly occur together
✓ Tissues become blue red(cyanotic)
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Hyperemia and Congestion
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HEMORRHAGE
❑ Is extravasation of blood into the extravascular space.
✓ An increased tendency to haemorrhage occurs in a wide variety
of clinical disorders collectively called haemorrhagic diatheses.
➢ Can be external or can be confined within a tissue; any accumulation
is referred to as a hematoma.
➢ Causes include:-
✓ Physical trauma to vessels or
✓ Platelet & Coagulation abnormalities.
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HEMORRHAGE Cont’d…
❑ Haematoma:- haemorrhage enclosed within a tissue or a cavity.
✓ Minute (1- to 2-mm) haemorrhages into skin, mucous membranes,
or serosal surfaces are called Petechiae (Pinpoint haemorrhages)
✓ This is typically seen in association with locally increased IV
pressure and thrombocytopenia.
✓ Slightly larger ( > 3mm) haemorrhages are called Purpura.
✓ Usually occurring due to trauma or vasculitis, or increased
vascular fragility.
✓ Larger (>10mm) subcutaneous hematomas are called Ecchymoses
✓ Typically occurs in trauma
❖ Clinical significance of haemorrhage depends on the volume and
rate of blood loss & site of bleeding
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❑ Purpura - ≥ 3mm hemorrhage
✓ ed local hydrostatic pressure
✓ Thrombocytopenia
✓ Defective platelet function
✓ Clotting factor deficits
✓ Trauma
✓ Vasculitis
✓ Increased vascular fragility
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❑ Ecchymosis :- > 1-2cm
✓Aka – bruises
(subcutaneous hematoma)
✓ Typical after trauma
✓ Exacerbated by other
conditions
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❑ Accumulations of blood in body cavities
❖ Haemothorax:- Pleural cavity
❖ Hemopericardium:- Pericardial cavity
❖ Hemoperitoneum:- Peritoneal cavity
❖ Hemarthrosis:- Joint cavity
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Effect or Clinical significance of hemorrhage
❑ Depends on
1. Volume and rate of blood loss
✓ Slow loss of larger amounts→ little impact.
✓ Rapid loss of > 20% - hypovolemic shock and death.
✓ Minimal chronic loss→ anemia.
2. Site of hemorrhage
✓ Small hemorrhage in subcutaneous tissue→ minimal or no effect
✓ Small hemorrhage to brain→ May be fatal.
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Fatal intracerebral bleeding (has a fatal outcome)
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Hemostasis and thrombosis
❑ Hemostasis
✓ is a sequence of events leading to the cessation of bleeding by
the formation of a stable fibrin-platelet hemostatic plug.
✓ It involves interactions between the vascular wall, platelets, and
the coagulation system.
✓Haemostasis is a vital process that maintains blood in a clot-free
fluid state under normal conditions and yet, following endothelial
injury, rapidly forms a clot to prevent further bleeding and initiate
healing.
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Hemostasis and thrombosis
❑ Thrombosis
✓ Is the pathologic formation of an intravascular fibrin-platelet
thrombus during life.
✓ Inappropriate activation of normal hemostatic process:
➢ Clot(thrombus) in uninjured vessel
➢ Thrombotic occlusion of a vessel after minor injury
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❑ Factors involved in thrombus formation (Virchow’s triad) include:
1. Endothelial injury due to atherosclerosis, vasculitis, or other
2. Alterations in laminar blood flow predisposing for DIC occur
with stasis of blood, turbulence, and hyper viscosity of blood
3. Hypercoagulability of blood:- can be seen with clotting
disorders, tissue injury, neoplasia; nephrotic syndrome;
advanced age; pregnancy; and oral contraceptives.
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Hemostasis and thrombosis……
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Hemostasis and thrombosis…..
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❖ Both hemostasis and thrombosis depends on 3 components:
✓ Vascular wall (Endothelium)
✓ Platelet
✓ Coagulation cascade(pathways)
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Hemostasis and thrombosis…..
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Normal hemostasis
❑ Sequence of events at sites of vascular injury:
1. Arteriolar vasoconstriction
2. Primary hemostasis(platelet plug)
3. Secondary hemostasis:- fibrin deposition
4. Permanent plug by XIII
✓ Polymerized fibrin and platelet aggregate
5. Counter regulatory response
✓ Restricts hemostatic plug at site of injury
✓ Tissue plasminogen activator
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Haemostasis and Blood Coagulation
❑ Whenever a vessel is injured(ruptured or severed), haemostasis is
achieved by several mechanisms:-
✓Vascular spasm(vasoconstriction)
✓Formation of platelet plug(primary haemostasis)
✓ Formation of blood clot as a result of blood
coagulation(secondary haemostasis).
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...
✓ Eventual growth of fibrous tissue into the blood clot to
close the defect permanently.
✓ Counter regulatory mechanisms
Haemostasis and Blood Coagulation…
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Platelets adhere to exposed ECM via von Willebrand factor (vWF)
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Local activation of the coagulation cascade results in fibrin polymerization
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Primary hemostasis
✓ Initially vWF binds to matrix collagen
✓ Platelets bind to vWF via their GPIb receptor & become activated.
✓ Activated platelets release its α and δ granules
✓ TXA2:- Phospholipase A2 breakdown of PL release TXA2
✓ α granules release:- clotting factor, Fibrinogen & PDGF
✓ δ granules release:- SAC(Serotonin, ADP, Ca++)
N.B:- Platelet adhesion:- Sticky of platelet on non- platelet surface.
Platelet aggregation:- Sticky of platelet on platelet surface.
NB:- Deficiencies in vWF results in serious bleeding disorder
- Bernard- Soulier syndrome – deficiency of GPIb
- Glanzmann thrombasthenia- deficiency of GPllb/llla
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Secondary Haemostasis
❑ Coagulation Cascade
✓ It is a series of enzymatic conversions turning inactive
proenzymes to active forms.
✓ The end stage of blood coagulation is the conversion of soluble
plasma fibrinogen into insoluble fibrin polymer.
❑ This is mediated by two pathways
✓ Intrinsic pathway
✓ Extrinsic pathway
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Secondary Haemostasis
1. Intrinsic pathway
➢ Following endothelial injury there is adsorption of the contact
factors , factor XII (Hageman factor )
➢ Factor XIIa activates factor XI to XIa
➢ This leads to conversion of factor X to Xa & eventually factor II
(prothrombin) to factor IIa (thrombin) which converts fibrinogen to
fibrin.
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Intrinsic system Extrinsic system
Contact
activation
Endothelial
injury
Hagman Factor
activation
Tissue Factor
Factor X
Final common
pathway
Prothrombin
Thrombin
Fibrinogen
Fibrin
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Secondary Haemostasis……
2. Extrinsic pathway
✓ This is activated by tissue factor, a lipoprotein complex exposed at
sites of tissue injury.
✓ The initial step involves the binding of factor VII, tissue factor and
calcium ions.
✓ Factor X becomes activated and then activates factor VII which
activates more factor X (positive feedback)
✓ Once factor Xa is formed the formation of thrombin and fibrin
occurs as in intrinsic pathway
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Intrinsic system Extrinsic system
Contact
activation
Endothelial
injury
Hagman Factor
activation
Tissue Factor
Factor X
Final common
pathway
Prothrombin
Thrombin
Fibrinogen
Fibrin
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Fibrinolysis
➢ Haemostatic plugs must be removed once healing is completed
(Haemostasis is secured).
➢ Blood contains an enzymatic system which lyses fibrin and blood
clots – the fibrinolytic system.
➢ This system includes plasminogen which can be activated to
plasmin by plasminogen activators.
✓ Plasmin cleaves and inactivates fibrin, factors V and VIII.
✓ Plasminogen can be activated by tissue plasminogen activator (t-
Pa), urokinase-like plasminogen activator (u-Pa) and kallikrein
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I. ENDOTHELIUM
✓ Antithrombotic and prothrombotic properties.
✓ The balance between antithrombotic & prothrombotic activities
determines whether thrombus formation, propagation or dissolution
occurs.
✓ Intact endothelium – antithrombotic
✓ Injury or activation – prothrombotic
➢ Hemodynamic factors, cytokines, infectious agents
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Antithrombotic properties
❑ Antiplatelet
✓ Endothelial plasma membrane, Prostacyclin(PGI2)
✓ Nitric oxide, Adenosine diphosphatase
❑ Anticoagulant
✓ Membrane associated heparin-like molecules:- bind A.T III
✓ Thrombomodulin:- thrombin receptor
❑ Fibrinolytic
✓ Tissue plasminogen activator(t-PA):- Convert plasminogen into
plasmin
✓ Clear fibrin deposits.
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Prothrombotic properties
❑ Platelet adhesion
✓ Exposure of ECM components
✓ Von Willebrand factor(vWF)
❑ Procoagulant
✓ Synthesis of tissue factor
✓ Augmentation of effects of clotting factors (IXa , Xa)
❑ Antifibrinolytic
✓ Inhibitors of plasminogen activator(PAIs)
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II. PLATELETS
❑ The interplay of PGI2 and TXA2 constitutes an exquisitely
balanced mechanism for modulating human platelet function:
✓ In the normal state, it prevents intravascular platelet
aggregation, but
✓ After endothelial injury it favors the formation of hemostatic
plugs.
✓ Play a central role in haemostasis
✓ On contact with ECM, platelets undergo three general reactions
1. Adhesion and shape change
2. Secretion
3. Aggregation
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III. COAGULATION CASCADE
✓ 3rd component of hemostatic process.
✓ Major contributor to thrombosis.
✓ Once activated the coagulation cascade must be restricted to the site
of vascular injury.
❑ Clotting is regulated by 3 anticoagulants:
1. Antithrombin III:- It inhibits activity of thrombin and other
factors like XIIa, XIa, Xa and IXa.
2. Protein c and s:- Vitamin K dependent proteins which
inactivate Va and VIIIa .
3. Plasmin:- degraded fibrine into fibrine degradation product
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THROMBOSIS
❑ Definition:
➢ The formation of a solid or semisolid mass from the constituents
of the blood within the vascular system during life.
❑ Pathogenesis:
➢ 3 predisposing factors for thrombus formation ( Virchow’s triad)
1. Endothelial injury
2. Stasis or turbulence of blood flow
3. Blood hypercoagulability
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1. Endothelial injury
❑ Most important factor in thrombus formation
✓ Will expose to highly thrombogenic sub endothelial ➔ Platelet
adherence & contact activation.
✓ E.g:- MI, HTN, vasculitis, Bacterial endotoxin & Smoking
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2. Stasis or Turbulence blood flow
❑ Normal blood flow is laminar.
❑ Stasis & turbulence
✓ Bring platelets to the surface, Reduce PGI2 , & t-PA
✓ E.g:- Atherosclerotic plaque, Aneurysms, MI, Hyper viscosity
syndromes like polycythemia, and Sickle cell disease.
✓ Stasis:- Major factor in venous thrombi
✓ Turbulence:- Arteries and cardiac thrombosis
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Endothelial injury disrupts the balance between prothrombotic and
Antithrombotic effects of the endothelium
Pro- and anticoagulant activities of endothelial cells
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3. Hypercoagulability
❑ Definition:
➢ Any alteration of the coagulation pathway that predisposes to
thrombosis
➢ It is a less common cause of thrombosis
❑ Can be divided in to:
✓ Primary(Genetic)
✓ Secondary(Acquired)
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1. Primary(Genetic)
✓ Mutations in factor V(Lieden factor) or prothrombin gene
✓ Antithrombin III deficiency and Protein C or S deficiency
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Hypercoagulability Cont’d…
2. Secondary (Acquired)
❑ Can be categorized into: High risk or Low risk
1. High risk for hypercoagulability
✓ Prolonged immobilization, MI, Artificial cardiac valves, DIC
✓ Tissue damage(surgery, burns fracture)
✓ Cancers(release procoagulant tissue products)
2. Low risk factors
✓ AF, Cardiomyopathy, NS, Oral contraceptives, Smoking
✓ Hyper estrogenic states E.g –pregnancy
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Morphology
❑ Can develop anywhere in the cardiovascular system
✓ Cardiac chambers ,Valve cusps, Arteries, Veins, Capillaries
❑ Variable size and shape
✓ Usually have area of attachment to the underlying vessel
(endothelium).
✓ When formed in heart or aorta thrombus may have apparent
laminations called Lines of Zahn.
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Arterial and Venous Thrombi
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Cont’d…
❑ The most common site of arterial thrombi In ascending order are:
✓ Femoral arteries
✓ Cerebral arteries
✓ Coronary arteries
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Fates of thrombus
I. Propagation
II. Embolization
III. Organization &recanalization
IV. Dissolution
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Fates of Thrombus Cont’d…
A. Propagation
➢ Thrombus may accumulate more platelets & fibrin and propagate
to cause vessel obstruction.
B. Embolization
➢ Dislodge & travel to other sites in the vasculature → Embolus→
obstruction of vessels → Death of tissues and cells ➔ Infarction
➢ E.g- Thromboembolism → Cerebral infarction
C. Organization and recanalization
→In growth of endothelial cells ,smooth muscle cells & fibroblasts
➔ Capillary channels → lumen formation ➔ Recanalization
D. Dissolution
✓ Thrombus may be removed by fibrinolytic activity.
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Clinical significance of thrombi…..
❑ Thrombi are clinically significant because:
✓ Causes blood vessel obstruction(arteries and veins)
✓ Possible sources of emboli
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Clinical effects of arterial &venous thrombi:
A. Venous thrombosis(phlebothrombosis)
✓ Affects the lower extremity veins~90%
✓ Divided in to :
1. Superficial and
2. Deep venous thrombosis
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1. Superficial venous thrombosis
✓ Usually occurs in saphenous venous system. E.g-in varicosities
✓ Predisposes to infection after slight trauma ➔ Varicous Ulcer
✓ Rarely embolizes
✓ Causes local edema ,pain ,tenderness (i.e. symptomatic)

Cont’d…
2. Deep Vein Thrombosis (DVT)
✓ May embolize, hence serious
✓ Occurs in deep veins of calf muscles
✓ May cause pain , edema
✓ Asymptomatic in ~50%, because of collateral bypass channels.
✓ Higher incidence in middle aged & elderly people ,due to
increased platelet aggregation & decreased PGI2 by
endothelium.

Cont’d…
❑ DVT has the following predisposing factors:
1. Trauma, surgery, burns-result in:-
1. Reduced physical activity
2. Injury to vessels
3. Procoagulant release from tissues
4. Reduced t-PA activity(fibrinolysis)
2. Pregnancy &puerperal states
✓ Increase coagulation factors& decrease synthesis of antithrombic
substances
3. Myocardial infarction& heart failure ➔stasis in the left side
4. Malnutrition, debilitating conditions (cancer..)
5. Inflammation of veins ( thrombophlebitis)

Cont’d…
B. Arterial thrombosis
✓ Commonest predisposing factor - Following abnormal vessel
wall & turbulence
✓ May narrow or occlude the lumen of arteries such as coronary
& cerebral arteries ➔ Myocardial & cerebral infarctions
✓ MI → Dyskinetic contraction& endocardial damage.
❑ Cardiac thrombi
✓ Caused by infective endocarditis, AF, & MI
✓ Common in valves & right auricular appendage.
✓ Arterial thrombi (esp. mural thrombi) may embolize to any
tissue, but particularly to the brain, kidneys, & spleen because
they receive large volume of blood.

Disseminated intravascular coagulation (DIC)….
✓ It is an acute or chronic thrombo hemorrhagic disorder occurring
as a result of progressive activation of coagulation pathway beyond
physiologic set point
✓ Occurs secondary to a variety of diseases resulting in failure of all
components of hemostasis.
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✓ It is characterized by activation of the coagulation sequence that
leads to formation of microthrombi throughout the microcirculation
of the body.
➢ As a consequence of thrombotic diathesis, there is consumption
of platelets, fibrin, and coagulation factors and, secondarily,
activation of fibrinolytic mechanisms
✓ Also called consumptive Coagulopathy.

Etiology & Pathogenesis
✓ DIC is not a primary disease but coagulopathy that occurs in the
course of variety of clinical condition
✓ DIC follows massive and/or prolonged release of soluble tissue
factors &/or endothelial-derived thromboplastin into the circulation
with generalized (pathologic) activation of coagulation system.
✓ It may result from pathologic activations of extrinsic &/or intrinsic
pathways of coagulation or impairment of clot inhibiting influences
Two mechanisms that trigger DIC
1. Release of tissue factor or thromboplastin substance into the
circulation
2. Wide spread injury to the endothelial cells
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Disseminated Intravascular Coagulation…

Etiology & Pathogenesis.......
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➢ DIC most likely follows sepsis, obstetric complications, advanced
malignancy and major trauma.
➢ Overall 50% are obstetric patient & 33% are due to carcinomatosis.

Clinical course
❑ The consequences of DIC are two fold:-
1. First, widespread deposition of fibrin with in the microcirculation.
➔ Ischemia of the more severely affected or vulnerable organs.
➔ Hemolytic anemia due to fragmentation of red cells
2. Second, hemorrhagic diathesis may dominate the clinical picture
because of consumption of platelets , clotting factors & increase in
fibrinolysis .
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Laboratory Investigation
❑ Laboratory investigations in DIC reveal that
✓ Platelet count is decreased
✓ Prolonged PT/TT
✓ Decreased fibrinogen
✓ Elevated fibrin split products (D-dimers)
➢ Cardinal laboratory manifestation of DIC is low plasma fibrinogen.
❑ The management is to treat the underlying disorder.
❑ Clinical features :-
✓Thrombosis may lead to organ dysfunction
✓Hemorrhage
✓Presence of petechiae and ecchymoses on skin

Morphology of DIC
❑ Microthrombi
✓ Found principally in arterioles and capillaries of kidney, and
Other organs like lung, GI mucosa, adrenals, brain and heart.
✓ Resulting ischemia leads to microinfarcts in renal cortex.

EMBOLISM
✓ Is a detached intravascular solid, liquid or gaseous mass that is
carried by blood to sites distant from its point of origin.
✓ 99% source is thrombus
✓ The emboli may also be composed of other types like atheroemboli,
fat emboli (most commonly with skeletal injuries), air emboli,
amniotic ﬂuid emboli and tumor emboli.
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EMBOLISM Cont’d…
✓ Emboli lodge in vessels too small to permit further passage,
resulting in a partial or complete vascular occlusion.
✓ The potential consequence of this is the ischemic necrosis of distal
tissue known as Infarction
✓ Depending on site of origin, emboli may lodge in the Pulmonary
or Systemic circulations.
89

Pulmonary Emboli
❑ Most of the pulmonary emboli arise in the deep leg veins above the
level of the knee.
✓ Paradoxical embolus is a rare embolus that can pass through an
ASD or VSD, thereby entering the systemic circulation.
✓ Most pulmonary emboli (60% to 80%) are clinically silent
because they are small.
➢ They rarely may cause pulmonary infarction (because lungs have
dual blood supply from pulmonary and bronchial vessels)
❑ C/F - breathlessness, pleuritic pain, hemoptysis & pleural effusion.
➢ Sudden death may occur if > 60% of pulmonary circulation is
obstructed.

Systemic Thromboembolism
✓ Refers to emboli traveling with in arterial circulation
✓ Most (80%) arise from intra cardiac mural thrombi,
➢ 2/3 of which are associated with left ventricular wall infarcts .
➢ Remainder from aortic aneurysm, thrombi on ulcerated
atherosclerotic plaques
91
✓ Unlike venous emboli, tend to lodge primarily in one vascular bed
(lung), arterial emboli can travel to a wide variety of sites
✓ Major sites for arteriolar embolization are lower extremities (75%)
& the brain (10%), with the rest in the intestines, kidney & spleen

Fat embolism
✓ is characterized by pulmonary insufficiency, neurologic symptoms
(irritability, restlessness and even coma), anemia, and
thrombocytopenia (manifesting as diffuse Petechial rash).
✓ It is seen after fractures of long bones (which contain fatty marrow)
or after soft-tissue trauma.
✓ It is fatal only in 10% of cases.

Infarction
✓ Is an area of ischemic necrosis caused by occlusion of either the
arterial supply or venous drainage in a particular tissue.
➢ Nearly 99% of all infarcts result from thrombotic or embolic
events & almost all result from arterial occlusion.
➢ Less common causes include vasospasm and torsion of
arteries & veins (e.g., volvulus, ovarian, and testicular torsion).
❑ Morphology
✓ On gross examination infarcts tend to be wedge shaped with
occluded vessel at apex & Periphery of the organ forming base.
✓ The infarct microscopically has features of ischemic
coagulative necrosis.
✓ Brain is an exception, CNS infarct results liquefactive necrosis
The general sequence of tissue changes after infarction

Types of infarcts
❑ Infarcts are classified depending on:
a. The basis of their color (reflecting the amount of Hemorrhage)
I. Hemorrhagic Infract (red color)
II. Anemic infarcts (pale or white color)
b. The presence or absence of microbial infection
I. Septic- infected with bacteria
II. Bland – free of infection
94

Infarction Cont’d…
I. Hemorrhagic infarcts - It occurs in,
a. Venous occlusion (e.g., ovarian and testicular torsion).
b. Tissues with dual circulation (eg, lung), permitting flow of
blood from unobstructed vessel in to necrotic zone
c. In tissues that were previously congested because of sluggish
blood flow
d. When blood flow is reestablished to a site of previous arterial
occlusion & necrosis.
II. Anemic infarcts (pale or white color) occur in
✓ Occur with arterial occlusions in solid organs with end-arterial
circulation or single blood supply.
✓ E.g., Heart, Spleen, and Kidney.
✓ Where tissue density limits the seepage of blood from adjoining
capillary beds into the necrotic area.

Red and white infarcts.
A. Hemorrhagic, roughly wedge-shaped pulmonary red infarct.
B. Sharply demarcated white infarct in the spleen

Factors that determine the size &
development of an infarct
A. The nature of vascular supply
✓ The presence of dual blood supply occur in the lung, liver, hand
& forearm may also offset occurrence of infarction rapidly unlike
renal & splenic circulation, which have end arterial supply.
98
B. Rate of development occlusion;
C. Vulnerability susceptibility to hypoxia
D. Oxygen content of blood

SHOCK
✓ A state in which the failure of the circulatory system to maintain
adequate cellular perfusion
➢The end results are hypotension followed by impaired tissue
perfusion & cellular hypoxia.
❑ Types of shock
1. Hypovolemic shock
2. Cardiogenic shock
3. Septic shock
4. Anaphylactic shock
5. Neurogenic shock

1. Hypovolemic shock
❑ Shock resulting from loss of blood or plasma volume.
❑ Causes include:
• Hemorrhage, (fatal if >25% of body blood)
• Fluid loss from burns,
• Diarrhea & Vomiting.
2. Cardiogenic shock
✓ It results from myocardial pump failure.
❑ Causes
A. Myopathic : Acute MI, Myocarditis, DCMP & HOCMP,
B. Mechanical:- LV out flow obstruction e.g. Aortic stenosis
• Reduction in forward cardiac out put , Arrhythmia
• Valvular rupture & Cardiac tamponade

3. Distributive shock
✓ refers to a group of shock subtypes caused by profound peripheral
vasodilatation despite normal or high cardiac out put
❑ Cause
1. Septic shock
2. Anaphylactic shock
3. Neurogenic shock

4. Septic shock
❑ Definition: is a systemic response to severe infection mediated via
macrophage derived cytokines that target end organ receptors in
response to infection
✓ Septic shock: a kind of shock caused by systemic microbial
infection, most commonly by Gm negative infection (end toxic
shock) but can also occur with Gm +ve or fungal infections.
❑ Causes:
• Complicated infected burns or surgery
• Instrumentation of urogenital or biliary tracts
• Toxic shock syndrome
Pathogenesis: Peripheral vasodilatation→ pooling blood flow→
reducing tissue perfusion.

5. Neurogenic shock
❑ Neurogenic shock
✓ Shock may occur in setting of anesthetic accident or spinal cord
injury due to loss of vascular tone & peripheral pooling of blood
❑ Anaphylactic shock
✓ It is initiated by a generalized IgE mediated hypersensitivity
response, is associated with systemic vasodilation & increased
vascular permeability

Stages of shock
❑ Uncorrected shock passes through 3 important stages;
1. An initial non progressive phase:
✓ It is also called a period of early compensatory period,
✓ During a compensatory mechanisms are activated & perfusion of
vital organs maintained.
104
❑ The net effect is
→ Tachycardia, ↑HR→ ↑CO
→ Peripheral vasoconstriction →↑ABP
→ Renal conservation of fluid
➢ The fall in renal perfusion stimulate the RAAS

2. Progressive stage
✓ Characterized by tissue hypoperfusion with onset of worsening
circulatory & metabolic imbalances including acidosis.
➢ There is a wide spread tissue hypoxia.
➢ Anaerobic glycolysis results in excessive lactic acid production.
➢ Clinically, the patient may become confused & ed urine output.
105
3. irreversible stage
✓A stage at which, survival is not possible
✓ Widespread cell injury is caused by lysosomal enzyme leakage
✓ Myocardial contractile function worsens due to NO synthesis
✓ If ischemic bowel allows intestinal flora to inter the circulation,
endotoxic shock may be superimposed
✓ At this point, the pt has complete renal shut down due to ATN.

Morphology
❑ All organs affected in sever shock. The cellular & tissue change
induced by shock are essentially manifest as organ dysfunction
❖ Heart
✓ Focal or widespread coagulation necrosis, MI, AHF
❖ Brain
✓ Its dysfunction occur when cerebral auto regulation or
compensatory mechanism fail.
❖ Kidney
✓ Exhibits extensive tubular ischemic injury, i.e., ATN.
✓ Manifested as oliguria, anuria & electrolyte disturbance
106

CONT…..
❖ Lung
✓ In established shock pulmonary function may deteriorate
rapidly due to a combination of causes:
✓ Pulmonary edema, Alveolar collapse &
✓ Leucocytes accumulation as a result of infection. Infection
causes inflammation in alveolar space. This features
collectively known as shock of lung or ARDS
❖ GIT bleeding, DIC, Acute pancreatitis, Liver central lobular
necrosis, Water house - Fredrichsen syndrome
107

Clinical course of shock
✓ Pt may manifest a weak & rapid pulse, tachypnea & cool, clammy,
cyanotic skin.
✓ In septic shock, skin initially is warm & fleshed because of
peripheral vasodilatation.
✓ The pt may present with confusion, restlessness, decrease in
urine out put, coma & death.
❑ The prognosis varies with the origin of shock & its duration. 80-
90% of young pts with hypovolemic shock survive where as
cardiogenic shock & septic shock carry mortality rate up to 75%.
108

6/21/2022 109
DR. MYM

DR. MYM
6/21/2022 110

Reading Assignment
❖ Factors affecting the consequences of hemorrhage
❖ Ascites
6/21/2022 111
DR. MYM

Quiz 2
1. Elaborate risk factors for thrombosis
2. List fates of a thrombus
3. describe mechanisms of edema formation
6/21/2022 112
DR. MYM

Individual Assignment
1. Heart failure
2. Pulmonary edema & ARDS
3. Hepatic failure
4. Renal failure
5. Acute & chronic complications of DM
6/21/2022 113
DR. MYM

DR. MYM pathology for PHO unit 7(5).pdf

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DR. MYM pathology for PHO unit 7(5).pdf