Robbins Chapter 5: Hemodynamic Disorders, Transudate

Thrombosis and Shock Protein - poor edema (increased

hydrostatic pressure or reduced plasma
Edema - An abnormal increase in interstitial protein)
fluid within tissues. Individuals suffering from heart failure,
60% of lean body weight is water renal failure, hepatic failure,
o 2/3 of the bodys water = malnutrition
intracellular compartment
o 1/3 of the bodys water = Exudate
extracellular compartment Protein rich edema (increased
o 5% of total body water = blood vascular permeability)
plasma
Losses of >20% of blood volume lead to Transudate: def. protein-poor, s.g.< 1.012,
hemorrhagic shock secondary to hydrodynamic impairments
Edema def. fluid in interstitial tissue. Exudate: def. protein-rich, s.g.>1.012,
secondary to inflammation and increased
Pathophysiology: vascular permeability
Increased Impaired venous
Hydrostatic return (CHF, Hyperemia and Congestion
Pressure cirrhosis, Hyperemia def. active process of
thrombosis) arteriolar dilation leading to local
Arteriolar dilation increase in blood volume.
(heat) Congestion def. passive process of
increase in blood volume due to
Reduced Nephrotic
impaired outflow.
Plasma syndrome,
Chronic pulmonary congestion: septa
Oncotic Malnutrition,
thickened and fibrotic, hemosiderin-
Pressure Cirrhosis
laden macrophages (heart failure cells)
Lymphatic Inflammatory, Acute hepatic congestion: central veins
Obstruction Neoplastic, Post- and sinusoids are distended and there
surgical may be central necrosis.
Sodium Renal insufficiency, Chronic passive congestion: nutmeg
Retention Hyperaldosterone liver, centrilobular necrosis and hepatic
Inflammation Acute, Chronic, fibrosis (cardiac cirrhosis).
Angiogenesis
Hemorrhage
def. extravasation of blood because of
Fluid collections in different body cavities: vessel rupture. Accumulation is
Hydrothorax a hematoma.
Hydropericardium 1-2 mm petichiae: thrombocytopenia,
Hydroperitoneum (Ascites) uremia, clotting factor deficiencies
> 3 mm purpura: trauma, vasculitis,
Anasarca - Severe and generalized edema with amyloidosis.
wide spread subcutaneous tissue swelling. > 1-2 cm ecchymoses: trauma, clotting
factor deficiencies, worsened by all of
the above
o hemoglobin (red-blue)
 o bilirubin (blue-green)
o hemosiderin (gold-brown)
Hemostasis and Thrombosis
Normal Hemostasis:
1. Vasoconstriction - endothelin
2. Platelet adherence and activation - primary
hemostatic plug
3. Coagulation cascade stimulated by the
release of tissue factor - leads to activation of
thrombin - secondary hemostatic plug
4. Permanent plug counter regulatory
mechanisms [t-PA]
- Endothelium: has pro-coagulant and anti-
thrombotic properties.
- Intact endothelium is anti-platelet (PGI2, NO,
ADP), anti-coagulant (heparin-like molecules,
thrombomuodulin, antithrombin III), fibrinolytic
(t-PA)
- Endothelial injury leads to adhesion of
platelets via vWF, synthesizes tissue factor (TNF,
IL-1), PAIs (plasminogen activator inhibitors)
Platelets
Alpha granules: P-selectin, fibrinogen,
fibronectin, factor V, vWF, plateket
factor 4, PDGF, TGF-b
Dense bodies (d granules): ADP, ATP,
Ca, histamine, serotonin, epinephrine
Adhesion: vWF - glycoprotein Ib,
fibrinogen
Secretion: granules, ADP mediates
aggregation
Aggregation: ADP, TXA2, thrombin,
platelet contraction, GpIIb-IIIa receptors
Clotting Cascade
Once activated must be restricted to
the site of vascular injury to prevent
clotting of the entire vascular tree.
Antithrombin III: inactivates IX, X, XI, XII
and II
Protein C & S: inactivate V and VIII
Plasmin: breaks down fibrin into FSP
(fibrin split products), which can act as
local, weak anticoagulants
urokinase-like tPA, tissue-type tPA
PGI2: vasodilator, inhibits platelet
aggregation
TXA2: vasoconstrictor, activates platelet
aggregation (aspirin blocks synthesis, by
acetylating cyclooxygenase)
Thrombosis
Virchow's triad: endothelial injury,
stasis, hypercoagulability
Hypercoagulable states: Factor V
Leiden, Protein C/S deficiency,
homocysteine, prothrombin mutations
Hyperestrogenic states (pregnancy,
OCP): increased hepatic synthesis of
certain coagulation factors and reduced
synthesis of antithrombin III.
Disseminated cancers: procoagulant
tumor products
Age: increasing platelet aggregation and
reduced PGI2.
Factor V Leiden
Clinical: 2-15% white population
Pathophysiology: Mutant factor V
Leiden cannot be inactivated by
protein C
Cytogenetics: arginine glutamine
at position 506
Heparin-Induced Thrombocytopenia
Clinical: 5% of population
Pathophysiology: Rx with
unfractionated heparin results in
formation of antibodies to
heparin platelet factor 4.
Treatment: low molecular weight
heparin preparations, retain
anticoagulant activities but do not
interact with platelets
Antiphospholipid Antibody Syndrome
Clinical: Multiple thromboses
associated with high serum titers
 to membrane phospholipids
(cardiolipin). Autoimmune
associated type exists.
Recurrent venous or arterial
thrombi, repeated miscarriages,
cardiac valce vegetations,
thrombocytopenia, 7% increased
risk of sudden death.
Two clinical groups: one
associated with SLE, the other
shows only hypercoagulability
without lupus.
Arterial thrombi occur in sites of
injury while venous occur due to
stasis.
Transmission:
Pathophysiology: Abs interfere with
coagulation in vitro but induce
hypercoagulative state in vivo (via direct
platelet activation, PGI2 or protein C
inhibition)
Micro: Lines of Zahn imply thrombosis at
sites of blood flow. Arterial thrombi
(retrograde propagation) at coronary,
cerebral and femoral arteries. Venous
thrombi propagate in the direction of
blood flow; 90% lower extremities.
Diagnosis: False positive VDRL (embedded
in cardiolipin). Also present in 5-15% of
normal individuals.
Treatment: Anticoagulation with aspirin,
heparin, coumadin, prednisone for
recurrent miscarriages and
immunosuppression in refractory cases.
Fate of a Thrombus:
1. Propagation
2. Embolization
3. Dissolution
4. Organization & Recanalization.
With older thrombi extensive fibrin
polymerization renders the thrombus
more resistant to proteolysis.
May become a culture medium for
bacteria - mycotic aneurysm.
Venous thrombi: asymptomatic in 50%. Risk
factors include CHF, trauma, surgery, burns,
puerperal and postpartum states, disseminated
cancers (see TRousseau's syndrome - migratory
thrombophlebitis).
Cardiac thrombi: brain, kidneys and spleen are
prime targets.
DIC is a potential complication of any condition
associated with widespread activation of
thrombin.
Embolism def. detached intravascular solid,
liquid, or gaseous mass that is carried by the
blood to a site distant from its point of origin.
99% are dislodged thrombi.
Pulmonary Thromboembolism
Clinical: 20-25/100,000
hospitalized patients; 95% from
deep leg vein thrombi above the
knee.
Rarely may pass through an
interatrial or interventricular
defect to gain access to the
systemic circulation (paradoxical
embolism).
60-80% clinically silent (small).
When 60% or more of the
pulmonary circulation is
obstructed leads to sudden death,
right heart failure or
cardiovascular collapse.
Micro: Usually causes pulmonary
hemorrhage not infarction(dual
blood supply) unless in the setting
of left sided cardiac failure.
Systemic Thromboembolism
Clinical: 80% arise from
intracardiac mural thrombi (2/3
assoc with LVW infarcts, 1/4 with
dilated L atria); remainder arise
from aortic aneurysms, plaques or
valve vegetations. 75% go to
lower extremities and 10% go to
the brain.
Fat Embolism
Clinical: After fractures of long
bones, soft tissue trauma or
burns. 90% of individuals with
severe skeletal injuries, though
<10% have any clinical findings.
Fat embolism syndrome begins 1-
3 days after injury with
tachypnea, dyspnea and
tachycardia, neurologic sx, diffuse
petechial rash (20-50%),
thrombocytopenia, anemia.
Pathophysiology: Mechanical
obstruction and biochemical
injury. Free fatty acids cause local
toxic injury to endothelium,
platelet activation.
Prognosis: Syndrome fatal in 10%.
Air Embolism
AKA: Decompression sickness,
"the bends" or "the chokes",
caisson disease
Clinical: In excess of 100cc
required to have a clinical effect.
Painful muscle cramps,
respiratory insufficiency,
neurological sx.
Pathophysiology: Formation of
gass bubbles within skeletal
muscle, soft tissues and joints
causes pain. Focal ischemia to
brain and heart.
Micro: Pulmonary edema and
hemorrhage, focal atelectasis or
emphysema. Persistence of gas
emboli in the skeletal system
leads to multiple foci of ischemic
necrosis (femoral head, tibia and
humerus).
Amniotic Fluid Embolism
Clinical: 1 in 50,000 deliveries.
80% mortality rate. Sudden
severe dyspnea, cyanosis, and
hypotensive shock, followed by
seizures and coma. Pulmonary
edema and DIC.
Micro: Pulmonary
microcirculation with epithelial
squamous cells shed from fetal
skin, lanugo hair, fat from vernix,
mucin from GI tract. Pulmonary
edema and DAD. Systemic fibrin
thrombi (DIC).
Infarction
def. area of ischemic necrosis caused by
occlusion of either arterial supply or
venous drainage. 99% from thrombotic
or embolic events. Remainder: local
vasospasm, extrinsic compression,
hemorrhage within a plaque, torsion,
traumatic rupture. Infarcts caused by
venous thrombosis are more common
in organs with single venous outflows:
e.g. testis, ovary.
Red Infarct (hemorrhagic): venous
occlusions, loose tissues (lung), dual
circulations, congested, when flow
reestablished
White Infarcts (anemic): arterial
occlusions or solid organs (heart,
spleen, kidney).
Micro: wedge-shaped, overlying
fibrinous exudate, margins better
defined with time.
minutes to hours - usu no demonstrable
changes
o 12-18 hrs hemorrhage
o few hours to 1 -2 days -
inflammatory response,
parenchymal regeneration
Factors That Influence Development of an
Infarct:
1. vascular supply
2. rate of development of occlusion
(time for development of alternate
perfusion pathways)
3. vulnerability of the tissue to
hypoxia (neurons 3-4 minutes,
 myocardium 20-30 minutes)
4. the blood oxygen content (e.g. Stages of Shock:
ventilation) nonprogressive (compensated),
progressive (widespread hypoxia),
Shock irreversible
Cardiogenic - myocardial pump failure o brain - ischemic
Hypovolemic - loss of blood or plasma encephalopathy
volume o heart - contraction band
Septic - 25-75% mortality rate; 70% necrosis
gram-negative bacilli. Endotoxins are o kidneys ATN
LPS released when cell wall is degraded. o lungs DAD
LPS directlt activates complement. o adrenal - cortical cell lipid
Monocytes respond by producing TNF, depletion
IL-1 fever and synthesis or acute phase o GI tract - patchy mucosal
reactants. hemorrhages
o systemic vasodilation o liver - fatty change, centilobular
o dec. myocardial contractility necrosis
o endothelial injury -> leukocyte
adhesion -> ARDS Prognosis: varies with origin and duration. 80-
o DIC 90% of young, healthy survive hypovolemic
o Neurogenic - spinal cord injury, shock with management. 75% mortality for
anesthesia cardiogenic shock with MI and gram negative
o Anaphylactic - IgE mediated septic shock.