HEMODYNAMIC DISORDERS,

THROMBOEMBOLIC DISEASE, AND

SHOCK

ARNEL G. BAYOTAS, RMT, AMT, MD., DPSP

Anatomic and Clinical Pathologist
Hemodynamic Disorders
• Hemodynamics deals
with flow and
distribution of blood
and fluids within the
body

• Hydrostatic pressure

• Osmotic pressure
 EDEMA
• What is edema?
• Edema is accumulation of
fluid in the interstitial
spaces and the body
cavities.
• Classification according to
the distribution of the fluid:
• Localized edema
• Generalized edema
• Anasarca marked by
profound swelling of
subcutaneous tissues &
accumulation of fluid in
the body cavities
• Classification according to fluid
composition
• Transudate
• Noninflammatory edema
• Increased hydrostatic pressure
• Reduced intravascular colloid
• Protein poor
• sp. gr: < 1.012
• Exudate
• Inflammatory edema
• Increased vascular permeability
• Protein-rich
• Sp.gr: > 1.020
 Classification according to their
pathogenesis

Modified from Leaf A, Cotran RS: Renal Pathophysiology, 3rd ed. New York,
Oxford University Press, 1985, p 146.
INCREASED HYDROSTATIC PRESSURE

• Local increase in IV pressure – impaired

venous return
• Deep venous thrombosis in lower ext. →
EDEMA
• Generalized increases in venous pressure
→ systemic edema
• CHF
• pathophysiologic state in which impaired cardiac function is unable to
maintain an adequate circulation for the metabolic needs of the tissues
of the body
PATHWAYS TO SYSTEMIC EDEMA
DECREASED PLASMA ONCOTIC
PRESSURE
• Decreased protein synthesis
• Increased protein loss
• Inadequate protein intake - kwashiorkor
• Hypoproteinemia (less than 5 g/dl) →
ANASARCA
• The examples of edema by this mechanism:
• Edema of renal disease e.g. in nephrotic syndrome, acute
glomerulonephritis.
• Ascites of liver disease e.g. in cirrhosis of the liver
• Protein malnutrition
Lymphatic Obstruction
• Lymphedema – localized edema due to impaired
lymphatic channels caused by an inflammatory or
neoplastic conditions
• The examples of lymphoedema include the
following:
• Removal of axillary lymph nodes in radical
mastectomy for carcinoma
• Pressure from outside on the main abdominal or
thoracic duct
• Inflammation of the lymphatics as seen in filariasis
• Occlusion of lymphatic channels by malignant cells
• Milroy’s disease or hereditary lymphedema
Sodium and Water Retention
• Causes both Inc. hydrostatic pressure (due to volume
expansion) and diminished vascular colloid osmotic
pressure (due to dilution)
• Occurs in:
• Kidney disorders (HYPOPERFUSON→ activation of RAAS
system)
• Cardiovascular disorders (e.g. CHF) – dec. CO → Inc.
Hydrostatic pressure → EDEMA & EFFUSIONS
Sodium and Water Retention
• Examples of edema by these mechanism
• Poststreptococcal glomerulonephritis
• Acute renal failure
• Excessive salt intake with renal insufficiency
• Increased tubular reabsorption of sodium
• Renal hypoperfusion
• Increased renin-angiotensin-aldosterone secretion
Inflammation
• Common cause of increased vascular
permeability

• Acute & chronic inflammation

• Histamine
• C3a and C5a
• Bradykinin
• PAF
• leukotrienes
General Morphology of EDEMA

• GROSS: enlarged due to swelling; cut surface

bulges outwards and is slightly opaque

• MICROSCOPIC: clearing and separation of the

extracellular matrix and subtle cell swelling
• Organ most commonly involved:
• Subcutaneous tissues
• Lungs
• Brain
Clinical consequences of edema
• Subcutaneous edema - Impair wound
healing or infection
• Pulmonary edema - Impedes gas exchange
& inc. Risk of infection
• Brain edema – impede cerebral blood flow
or cause herniation – compromising
medullary centers
 DISTURBANCES IN THE
VOLUME OF CIRCULATING
BLOOD

HYPEREMIA AND CONGESTION

 Hyperemia Congestion

Type active process passive process

Tissue Affected tissues turn red dusky reddish-blue

morphology (erythema) color (cyanosis)

Mechanism Inc. Arteriolar dilation Stagnation of blood

mediated by: in capillaries
 Vasoactive mediators caused by Dec.
Hormones venous outflow
neurogenic reflexes
Examples Inflammation CHF
Exercise DVT
Blushing
Effects of Long standing Chronic
CONGESTION
• Inadequate tissue perfusion & persistent
hypoxia → parenchymal cell death & tissue
fibrosis (scarring)
• ↑ intravascular pressures
• Cause edema
• Capillary rupture → focal hemorrhage
 How does passive congestion affect the lungs?
• Acute Passive Congestion • Chronic Passive Congestion

Dilated
alveolus
with edema
fluid

blood-engorged alveolar Heart

capillaries and variable failure cells
degrees of alveolar
Septal edema and
intraalveolar hemorrhage
 How does congestion affect the liver?

ACUTE PASSIVE CONGESTION, CHRONIC PASSIVE CONGESTION,

LIVER LIVER

 distended central vein and  red brown and slightly depressed

sinusoids centrilobular regions
Centrilobular hepatocytes can  nutmeg liver
be ischemic
Fatty change in periportal
hepatocytes
Necrosis with degenerating hepatocytes and hemorrhage

Liver with
chronic
passive
congestion
and
hemorrhagic
necrosis

(Courtesy of Dr. James Crawford, Department of Pathology, University of

Florida, Gainesville, Florida.)
HEMOSTASIS &
THROMBOSIS
HEMOSTASIS and THROMBOSIS
• Normal, physiologic  Inappropriate activation
process maintaining of blood clotting in
uninjured vasculature
blood in a fluid, clot-
 Thrombotic occlusion of a
free state w/in normal
vessel after minor injury
vessels while inducing
localized hemostatic
plug at sites of
vascular injury
Sequence of events in HEMOSTASIS
Sequence of events in HEMOSTASIS
Key PLAYERS: Hemostasis &
thrombosis
•ENDOTHELIUM
•PLATELETS
•COAGULATION
“CASCADE”
ENDOTHELIUM
• NORMALLY
• ANTIPLATELET PROPERTIES
• ANTICOAGULANT PROPERTIES
• FIBRINOLYTIC PROPERTIES
• IN INJURY
• PRO-COAGULANT PROPERTIES
 Antithrombotic Properties
Antiplatelet Anticoagulant Fibrinolytic
effects effects effects
 Intact endothelium endothelial membrane-  tissue-type plasminogen
Prevent platelet adhesion associated heparin-like activator
& aggregtion molecules (t-PA),
 prostacyclin (PGI2)
 nitric oxide  thrombomodulin
 elaborate adenosine
diphosphatase  tissue factor pathway
Inhibits platelet inhibitor
aggregation
ENDOTHELIUM
Prothrombotic properties
Platelet Procoagulant Antifibrinolytic
effects effects effects
•Allows • synthesize • secrete
platelet tissue factor inhibitors of
adhesion •Augment plasminogen
through catalytic activator (PAIs)
interactions function of IXa
with von & Xa
Willebrand
factor (vWF
PLATELET PHASES
• ADHESION
• Platelets rapidly change shape
• SECRETION (i.e., “release” or
“activation” or
“degranulation”)
• AGGREGATION
• CONTRACTION
Platelet adhesion and aggregation
COAGULATION “CASCADE”

• INTRINSIC(contact)/EXTRINSIC(TissFac)
• ProenzymesEnzymes
• Prothrombin(II)Thrombin(IIa)
• Fibrinogen(I)Fibrin(Ia)
• Cofactors
• Ca++
• Phospholipid (from platelet membranes)
• Vit-K dep. factors: II, VII, IX, X, Prot. S, C
Source: Mary L. Turgeon, EdD, MT(ASCP)
COAGULATION “CASCADE”
The coagulation cascade in the
laboratory and in vivo
Standard Assays in Coagulation
Pathways
• prothrombin • partial
thromboplastin
time (PT)
time (PTT)
• extrinsic • intrinsic pathway
pathway (factors XII, XI, IX,
(factors VII, X, VIII, X, V, II, and
fibrinogen)
II, V, and
fibrinogen)
Factors That Limit Coagulation
What is hemorrhage?
• Definition: extravasation of blood into the extravascular
space

• Rupture of a blood vessels due vascular injury→ severe

hemorrhage
• Massive bleeding due ruptures of large vessels
• Subtle bleeding due defects in clotting
• defects in von Willebrand factor
• aspirin consumption
• uremia (renal failure
DISTINCT PATTERNS OF HEMORRHAGE
HEMATOMA Hematoma is a grossly
visible accumulation of
extravasated blood in
the tissue
PETECHIAE 1 to2 mm Inc intravascuar pressure,
(skin, mucous thrombocytopenia,
membranes or serosal defective platelet function
surfaces)

PURPURA ≥ 3 mm Same w/ petechiae,

trauma, vasculitis, inc,
vascular fragility
(amyloidosis)

ECCHYMOSES ≥ 1 to2 cm subcutaneous Trauma , other bleeding

hematomas (bruises) disorders

HEMO-: -thorax, -pericardium, -peritoneum, HEMARTHROSIS

Factors affecting clinical significance of
HEMORRHAGE
• Volume/amount
• Rate of
bleeding/speed
• Location/site of
hemorrhage

Fatal intracerebral bleed

THROMBOSIS
• Pathologic counterpart of
hemostatsis
• Involves blood clot
formation (thrombus) w/in
intact vessels
• Inappropriate activation of
blood clotting in uninjured
vasculature
• Thrombotic occlusion of a
vessel after minor injury
THROMBOSIS
(Virchow’s triad)
THROMBOSIS
Endothelial injury
• Mechanisms of thrombus formation:
• Physical loss of endothelium → exposes
subendothelial vWF and tissue factor
• Platelet adhesion
• Release of tissue factor
• Depletion of PGI2 and plasminogen activators
• Downregulate the expression of:
• Thrombomodulin
• Protein C - factors Va & VIIIa inhibitor
• Tissue factor protein inhibitor
• Tissue plasminogen activator (tPA)
• Secretion of plasminogen activator inhibitors (PAIs)
THROMBOSIS
Endothelial injury
• CAUSES:
• hypertension,
• turbulent blood flow
• bacterial endotoxins
• radiation injury
• homocystinemia or hypercholesterolemia
• toxins absorbed from cigarette smoke
Alterations in Normal Blood Flow
• Laminar - Normal blood flow
• Turbulence
• arterial and cardiac thrombosis
• Ulcerated atherosclerosis

• Stasis
• major contributor in the development of venous thrombi
• Aneurysm create local stasis
• Hyperviscosity syndrome (polycythemia)
• Deformed RBC in sickle cell anemia
Mechanisms of Turbulence & Stasis
promoting THROMBOSIS
• Disrupt laminar flow and bring platelets into contact with
the endothelium
• Prevent washout and dilution of activated clotting factors
by fresh flowing blood
• Retard the inflow of clotting inhibitors
• Promote endothelial cell activation
HYPERCOAGULABILITY
• AKA: thrombophilia
• any alteration of the coagulation pathways that
predisposes to thrombosis
• less frequent contributor to thrombotic states
• important role in venous thrombosis
• Two Forms:
• Primary (genetic)
• Mutation in factor V and prothrombin gene
• Secondary (acquired) disorders
HYPERCOAGULABILITY
MORPHOLOGY OF THROMBI
• Arterial or cardiac • venous thrombi
thrombi • Stasis
• Turbulence (vessels • extend in the direction of
bifurcation) or blood flow
endothelial injury
atheroma, endocarditis)
• arterial thrombi tend to
grow retrograde from the
point of attachment
MORPHOLOGY OF THROMBI
• lines of Zahn
• Represent pale platelet &
fibrin deposits alternating
w/ darker red cell layers

• Distinguish antemortem
thrombosis from
postmortem clot
 MORPHOLOGY OF THROMBI
Mural thrombi Arterial thrombi
grow retrograde
from the point of
attachment
• heart chambers • frequently occlusive
• Abnormal myocardial • M/C sites involvement:
contraction • coronary, cerebral,
• endomyocardial injury and femoral arteries
• aortic lumen • consist of a friable
•ulcerated meshwork of platelets,
atherosclerotic plaque fibrin, red cells, and
• aneurysmal dilation degenerating leukocytes
•Underlying cause:
•ruptured
atherosclerotic plaque
•vascular injuries
(vasculitis, trauma)
Venous thrombosis
(phlebothrombosis)
extend in the
direction of blood
flow
• occur at sites of stasis
•invariably occlusive
•contain more enmeshed
red cells (and relatively few
platelets)
•M/C sites involvement:
•veins of the lower
extremities are most
commonly involved
(90% of cases)
Thrombus Postmortem clot

Chicken fat

currant jelly
 FATE of THROMBI
• PROPAGATION
(Downstream)
• EMBOLIZATION
• DISSOLUTION
• ORGANIZATION &
RECANALIZATION
Clinical Consequences of Thrombus
• obstruction of arteries and veins
• sources of emboli
• Venous thrombi
• congestion and edema in vascular beds
• capacity to embolize to the lungs and cause death
• Infarctions – arterial thrombi
Embolism
• A detached intravascular solid, liquid, or gaseous
mass that is carried by the blood to a site distant from
its point of origin

• Almost all emboli represent some part of a dislodged

thrombus, hence the term thromboembolism
Pulmonary thromboembolism
• Clinical and Pathologic features:
• 60% to 80% are clinically silent
• Can result to sudden death, cor pulmonale CV
collapse - ≥ 60% obstruction of pulmonary
circulation
• Can result to pulmonary hemorrhage due to
obstruction of medium sized arteries
• Embolism to small end-arteriolar pulmonary
branches → INFARCT
• Multiple emboli over time → pulomnary HPN &
right ventricular failure
Systemic embolism
• Emboli traveling in the • Major sites for arteriolar
arterial system embolization
• Most (80%) arise from • lower extremities (75%)
intracardiac mural • brain (10%)
thrombi • intestines, kidneys, spleen,
and upper extremities
• 2/3 assocd. with left
ventricular wall infarcts • The consequences of
embolization
• Another quarter (25%)
• Occlusion
with left atrial dilation
• Ischemia
and fibrillation (mitral
• Infarction
valve diseases)
• Paradoxical
• 10-15% - unknown origin
Fat embolism
• Causes;
• Most often due to traumatic fracture
• Trauma to fat-laden tissue
• Burns
• Pathogenesis
• Microglobules from BM → microvasculature of vital organ →
ischemia & hemorrhage
• Fatty acid from microglobules → damage the vessels endothelium
→ platelet thrombi formation
• Diagnosis:
• Clinical diagnosis
• Search of fat globules
AMNIOTIC FLUID EMBOLISM
• Embolization of amniotic fluid into maternal pulmonary
circulation
• Characteristics:
• Sudden onset of:
• severe dyspnea
• cyanosis, and shock,
• neurologic impairment ranging from headache to seizures and
coma
AMNIOTIC FLUID EMBOLISM
• Pathogenesis/ underlying cause:
• infusion of amniotic fluid or fetal tissue
into the maternal circulation via a tear
in the placental membranes or rupture
of uterine veins
HISTOLOGIC FINDINGS: AMNIOTIC
FLUID EMBOLISM
• squamous cells
shed from fetal skin
• lanugo hair, fat from
vernix caseosa, and
mucin
• marked pulmonary
edema, diffuse
alveolar damage
• fibrin thrombi
 AIR EMBOLISM
• Refers to gas bubbles within the circulation that obstruct
vascular flow & cause ischemia
• more than 100 cc of air are required to have a clinical
effect in the pulmonary circulation
• Obstetrical /laparoscopic procedures
• After chest wall injury
 FORMS OF AIR EMBOLISM
bends rapid formation of gas bubbles within skeletal
muscles and supporting tissues in and about joints
is responsible for the painful condition

chokes In the lungs, gas bubbles in the vasculature cause

edema, hemorrhage, and focal atelectasis or
emphysema, leading to a form of respiratory
distress

decompression Caused by sudden decrease in atmospheric

sickness pressure ; e.g scuba & deep sea divers

caisson disease A more chronic form of decompression sickness

Persistence of gas emboli in the skeletal system
leads to multiple foci of ischemic necrosis
 INFARCTION
• Defined as an area of ischemic
necrosis* secondary to occlusion of
either the arterial supply or the
venous drainage.

• Nearly all infarct → thrombotic or

embolic arterial occlusion
Morphology of infarction
• Red infarcts • White infarcts
• Venous occlusions (e.g., • arterial occlusions in solid
ovary, testicular tortion) organs with end-arterial
• Loose tissues (e.g., lung) circulation
• Tissues with dual • (e.g., heart, spleen, and
circulations (e.g., lung kidney)
and small intestine)
• Tissues previously
congested by sluggish
venous outflow
• At a site of previous
occlusion & necrosis
(arterial angioplasty)
RED WHITE
INFARCT
INFARCTION FACTORS
• NATURE of VASCULAR SUPPLY
• RATE of DEVELOPMENT OCCLUSION
• SLOW (BETTER)
• FAST (WORSE)
• VULNERABILITY to ISCHEMIA
• Neurons vs. MYOCYTE vs. FIBROBLAST
• HYPOXEMIA
SHOCK
• systemic hypotension due either to
reduced cardiac output or to reduced
effective circulating blood volume
↓
Hypotension
↓
Hypoperfusion
↓
Cellular hypoxia
SHOCK
RARE Clinical Mechanisms
CAUSES settings
anesthetic accident loss of vascular
neurogenic or a spinal cord tone and peripheral
shock injury pooling of blood

systemic
Anaphylacti vasodilation and
c shock increased vascular
permeability caused
by an IgE–mediated
hypersensitivity
reaction
Major pathogenic pathways in septic shock
Major pathogenic pathways in septic shock
CLINICAL STAGES of shock
• NON-PROGRESSIVE
(compensatory mechanisms)
• PROGRESSIVE
(acidosis, early organ failure)
• IRREVERSIBLE
NON-PROGRESSIVE
• activation of reflex neurohumoral
COMPENSATORY MECHANISMS –
baroreceptor reflexes
• CATECHOLAMINES, R-AAS axis,
ADH, sympathetic stimulation
• PERFUSION OF VITAL ORGANS
IS MAINTAINED
PROGRESSIVE
• Widespread tissue HYPOXIA
• Aerobic respiration → ANAEROBIC
GLYCOLYSIS → LACTIC ACIDOSIS →
• Lowers tissue pH
• Blunts vasomotor response
• Arteriolar dilatation
• Peripheral pooling of blood

• EARLY “VITAL” ORGAN FAILURE

IRREVERSIBLE
• Widespread cell injury – lysosomal
enzyme leakage
• Myocardial contractility - ↑ NO
• Ischemic bowel – allow intestinal
flora to enter circulation
• Complete renal shutdown – due to
ATN & Renal failure

• HEMODYNAMIC CORRECTIONS of no
use
 Tissue morphology of shock
• Hypoperfusion and microvascular thrombosis → Hypoxic
injury → FAILURE OF MANY ORGANS
• Kidney – fibrin thrombi & acute tubular necrosis
• Adrenal - cortical cell lipid depletion → synthesis of STEROIDS
• GIT - focal mucosal hemorrhage and necrosis
• Lung - Diffuse alveolar damage → shock lung
 THANK YOU PATHO!!!

REFERENCE:
ROBBINS AND COTRAN PATHOLOGIC BASIS OF DISEASE, 9th
ed.