Download Lec.5 Dr. Methaq Mueen Hemodynamic Disorders Dissiminated I

Dr. Methaq Mueen
Lec.5
Hemodynamic Disorders
Dissiminated Intravascular Coagulopathy(DIC):
It is characterized by activation of coagulation sequence leading
to formation of thrombi throughout the microcirculation, then as
consequence of widespread thrombosis, there is consumption of
platelets coagulation factors & secondarily activation of
fibrinolysis.
Causes of DIC:
1. Obstetric causes:
Abruptio placentae, retained dead fetus, amniotic fluid embolism,
toxemia.
2. Infections:
 Sepsis (gram negative & gram positive septicemia).
 Meningococcemia.
 Fungal infection (histoplasmosis, aspergillosis).
 Malaria
3.Neoplasms:
Carcinomas of pancreas, prostate, lung, & stomach, acute
leukemia.
4.Massive tissue injury:
Trauma, burns, & extensive surgery.
5.Miscellaneous:
Shock, liver disease, heat stroke, giant hemangioma, vasculitis.
Pathogenesis of DIC;
Two major mechanisms may trigger DIC:
1. Release of tissue factor or thromboplastic substances into
the circulation.
2. Widespread endothelial cells injury.
DIC most likely follow sepsis, obstetric complications,
malignancy & major trauma (like trauma to the brain) then
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these factors initiate the formation of tissue factor leading to
widespread microvascular thrombosis, which result in
followings:
1. Vascular occlusion……. Ischemic tissue damage.
2. consumption of clotting factors & platelets……. Bleeding.
3. Activation of plasmin which results in proteolysis of clotting
factors ……….. Bleeding.
Or plasmin result in stimulation of fibrinolysis……… fibrin
degradation products (FDP)…………. Inhibition of thrombin &
platelets aggregation & fibrin polymerization which in further
bleeding.
Morphology of DIC:
1. Formation of microthrombi throughout the circulation: (in
the kidneys, adrenals, brain, & heart), in all these organs
result in ischemic necrosis (infarction).
2. Bleeding tendency: which result in foci of large
hemorrhage near the areas of infarction & widespread
petechiae & ecchymoses within skin, serosal surfaces, lungs,
urinary system & heart.
Clinical course of DIC:
 Acute DIC: usually follow obstetric complication (usual
presentation is bleeding tendency).
 Chronic DIC: Usually occur in patient with cancer
(presented with thrombotic complications).
 Bleeding tendency range from minimal bleeding to
hypovolemic shock with acute renal failure, dyspnea,
cyanosis, convulsions, & coma.
Lab investigations:
Thrombocytopenia, prolonged PT & PTT & Increased Fibrin
Degradation Products (FDP).
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Shock (vascular collapse):
It is a systemic hypoperfusion due to a reduction either in cardiac
output or in the effective circulating blood volume. Then
hypotension occurs followed by impaired tissue perfusion &
cellular hypoxia.
Classification of shock:
1- Hypovolemic shock: In which there is a loss of blood &
plasma volume.
Causes:
* Hemorrhage.
* Fluid loss as in severe vomiting, diarrhea & burns.
2- Cardiogenic shock: this type result from myocardial pump
failure Causes:
* Myocardial infarction.
* Ventricular arrhythmias.
* Rupture of the heart.
* Pulmonary embolism.
* Cardiac tamponade.
Mechanism of development:
Failure of myocardial pump due to intrinsic myocardial damage or
extrinsic pressure or obstruction to outflow .
3- Septic shock: (endotoxic shock)
Causes:
Overwhelming bacterial infection (gram negative septicemia or
endotoxic shock) or gram positive septicemia.
Mechanism of development:
* Peripheral vasodilatation & pooling of blood at periphery.
* Cell membrane injury & endothelial cell injury with DIC
(disseminated intravascular coagulopathy).
4- Neurogenic shock:
Causes:
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Anesthesia & spinal cord injury.
Mechanism: peripheral vasodilatation.
5. Anaphylactic shock:
Associated with IgE mediated hypersensitivity reaction……
generalized vasodilatation & increased vascular permeability…..
Relatively less blood volume….. Tissue hypoperfusion.
Stages of shock:
1- Non progressive phase: (compensatory phase), In this stage a
compensatory mechanisms operate to maintain cardiac output
&blood pressure near normal levels .
These compensatory mechanisms are included:
a- Arteriolar constriction leading to increase blood pressure.
b- Increase heart rate &cardiac output.
c- Retention of fluid through increase secretion of ADH &
activation of rennin angiotensin - aldosteron axis to
retain fluid.
Clinically patient presented as coolness & pallor of skin with
tachypnea. (Except septic shock the is warm, flushed skin)
2- Progressive phase :
If the underlying cause is not corrected, then the shock passes into
progressive phase, during which there is widespread tissue
hypoxia which is replaced by anaerobic cellular
respiration……lactic acid production……… metabolic lactic
acidosis……..low tissue PH…….. Arteriolar dilatation……..pooling of
blood at peripheral circulation…… decrease cardiac output &
induce DIC.
CLINICALLY Patient become confused, decreased urinary output.
3. Irreversible Phase: multiple organs failure
Without correction of previous phase, there is widespread
irreversible cell injury (due to free radicals injury, release of
lysosomal enzymes), e.g. low cardiac contraction, ischemic
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necrosis of bowel…….endotoxic shock, & complete renal
shutdown.
Pathological Changes of shock:
 Brain: Ischemic encephalopathy.
 Heart: coagulation necrosis
 Kidneys: acute tubular necrosis which lead to oliguria or anuria
& electrolytes disturbances.
 Lungs: diffuse alveolar damage (shock lung)…….. Respiratory
failure.
 Adrenals: cortical cell lipid depletion & use stored lipids for
synthesis of steroid
 GIT: patchy mucosal hemorrhage & necrosis (hemorrhagic
enteropathy).
 Liver: fatty change.
Prognosis:
 In hypovolemic shock: 80-90% of young patients survive.
 Cardiogenic shock associated with extensive myocardial
infarction & in gram-negative shock 75% died.
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Pathogenesis of endotoxic shock. Sepsis is caused primarily by gram-negative bacteria
and bacterial products such as endotoxin (lipopolysaccharide [LPS]), which is released into
the circulation, where it binds to a pattern recognition receptor on the surface of
monocyte/macrophages. Such binding stimulates the secretion of substantial quantities of
tumor necrosis factor-alpha (TNF-α). TNF-α mediates septic shock by a number of
mechanisms: (1) stimulation of the release of
various pro- and anti-inflammatory mediators; (2) induction of endothelial procoagulation
by tissue factor, thereby leading to thrombosis and local ischemia; (3) direct cytotoxic
damage to endothelial cells; (4) endothelial activation, which enhances the adherence of
polymorphonuclear leukocytes; (5) stimulation of endothelial cell nitric oxide production
and vasodilation; and
(6) release of chemokines to attract leukocytes for resolution and repair of tissue injury.
Ca2+, calcium ion; ICAM, intercellular adhesion molecule; IL, interleukin; iNOS, inducible
nitric oxide synthetase; MCP-1, monocyte chemotactic protein-1; MIP-2, macrophageinflammatory protein-2; NO, nitric oxide; VCAM-1, vascular cell adhesion molecule-1.
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