HEMODYNAMIC DISORDERS, THROMBOEMBOLISM AND PULMONARY CONGESTION
SHOCK Acute:
o Blood engorged alveolar capillaries
o Alveolar septal edema
o Intra-alveolar hemorrhage
Chronic:
o Septa become thicker and fibrotic
o Alveolar spaces contain numerous
macrophages laden with hemosiderin (heart
failure cells, can be seen in lungs) derived
from phagocytosed red cells
HYPEREMIA AND CONGESTION
Both have increase in blood volume, but:
o Hyperemia - active process resulting from
arteriolar dilation and increased blood inflow HEMOSIDERIN
o Congestion - passive process resulting from Iron-containing, golden brown, granular pigment
impaired outflow of venous blood from a
tissue
Lung
EDEMA
ACCUMULATION OF FLUID
EDEMA - within tissues
EFFUSION - within the adjacent body cavities
o Hydrothorax – within pleural cavity
o Hydropericardium - pericardial cavity
HYPEREMIA o Hydroperitoneum/Ascites - peritoneal cavity
active
inflow ANARSARCA
redder (arterial) Severe, generalized edema marked by profound
oxygenated blood swelling of subcutaneous tissues and accumulation
e.g., exercise, acute inflammation of fluid in body cavities
CONGESTION
passive
outflow
blue, red/cyanosis (venous)
deoxygenated blood
cardiac failure, venous obstruction
CONGESTION: NUTMEG LIVER
-dilated blood vessels
LYMPHEDEMA
” Elephantiasis”/Lymphatic filariasis
Wuchereria bancrofti
BREAST CANCER
PULMONARY EDEMA Causes edema of overlying skin
Pitted appearance of skin of the affected breast
called peau d’ orange (orange peel)
HEMORRHAGE
extravasation of blood from vessels
often the result of damage to blood vessels or
defective clot formation
Hemorrhagic diathesis
o wide variety of clinical disorders with
increased risk of hemorrhage
Hematoma
o blood accumulation within tissues
Large bleeds within the body cavities
Hemothorax – within pleural
Hemopericardium - pericardial cavity
Hemoperitoneum - peritoneal cavity
Hemarthrosis – within joints
-reduced in plasma albumin
GENERALIZED DEFECTS INVOLVING SMALL VESSELS
Ex of hematoma
HEMORRHAGHIC DISORDERS
EPISTAXIS - nosebleeds
MENORRHAGIA - excessive menstruation
THROMBOCYTOPENIA - very low platelet counts
HEMOSTASIS AND THROMBOSIS
HEMOSTASIS
series of regulated processes
culminates in the formation of a blood clot
1. ARTERIOLAR VASOCONSTRICTION
Vascular spasm
Occurs immediately after vascular injury; transient
Mediated by reflex neurogenic mechanisms and
augmented by the local secretion of factors such as
endothelin
THROMBOSIS
pathologic counterpart of hemostasis
results in formation of blood clot (thrombus) within
non- traumatized, intact vessels
2. PRIMARY HEMOSTASIS
Formation of platelet plug
Disruption of endothelium exposure of von
Willebrand factor (vWF) and collagen platelet
adherence and activation
Results in primary hemostatic plug
NORMAL HEMOSTASIS
process by which blood clot form at sites of vascular 3. SECONDARY HEMOSTASIS
injury which serves to prevent or limit the extend of Fibrin deposition
bleeding Tissue factor exposure Factor VII activation
orchestrated process involving: platelets, clotting Culminates in Thrombin formation and Fibrin
factors and endothelium meshwork
4. CLOT STABILIZATION AND RESORPTION
Polymerized Fibrin + platelet aggregates = solid,
permanent plug
Counterregulatory mechanisms (e.g., tissue
General sequence of hemostasis plasminogen activator) are activated: to limit clotting
1. Arteriolar vasoconstriction to the site of injury clot resorption and tissue
2. Primary hemostasis repair
3. Secondary hemostasis
4. Clot stabilization and resorption
PLATELETS: ADHESION AND AGGREGATION
PLATELETS
Anucleate, disc-shaped cell fragments shed into the
bloodstream from marrow megakaryocytes.
Forms the primary hemostatic plug
Provide surface that recruits, and concentrates
activated coagulation factors
PLATELET ADHESION
vWF (von Willebrand Factor): adhesion bridge
between platelet surface receptor glycoprotein Ib
(GpIb) and exposed collagen
PLATELET AGGREGATION
The GpIIb/IIIa receptors on activated platelets form
bridging crosslinks with fibrinogen, leading to
platelet aggregation.
PLATELET ACTIVATION
1. Platelets rapidly change in shape following
adhesion. INITIAL PLATELET PLUG/ PRIMARY HEMOSTASIS
Related changes:
Glycoprotein IIb/IIIa increases its affinity for
fibrinogen
Negatively charged phospholipids
(phosphatidyl serine) translocates to the
platelet surface
ASSOCIATED BLEEDING DISORDERS
Phospholipids bind calcium and serve as
nucleation sites for the assembly of von Willebrand disease (genetic deficiencies in
coagulation factor complexes. vWF)
Bernard-Soulier syndrome (genetic deficiencies in
GpIb)
Glanzmann thrombasthenia (inherited deficiency of
GpIIb-IIIa)
COAGULATION CASCADE
series of amplifying enzymatic reactions that lead to
the deposition of an insoluble fibrin clot.
each reaction step involves:
an enzyme (an activated coagulation factor)
a substrate (an inactive proenzyme form of a
coagulation factor)
a cofactor (a reaction accelerator)
Coumadin - a widely used anti-coagulant that
2. Release reaction/ Secretion of granule contents antagonizes the enzymatic reactions that produce γ-
Related changes: carboxylated glutamic acid and use vitamin K as
Adenosine diphosphate (ADP) is released cofactor.
Activated platelets also produce the
prostaglandin thromboxane A2 (TXA2), a PROTHROMBIN TIME (PT)
potent inducer of platelet aggregation. assesses the function of proteins in the extrinsic
Aspirin - inhibits platelet aggregation pathway (factors VII, X, V, II and fibrinogen)
and produces a mild bleeding defect
by inhibiting cyclooxygenase (COX), a
platelet enzyme that is required for
TXA2 synthesis.
PARTIAL THROMBOPLASTIN TIME (PTT)
assay screens the function of proteins in intrinsic
pathway (factors XII, XI, IX, VIII, X, V, II and
fibrinogen)
THROMBIN (IIA)
Conversion of fibrinogen into crosslinked fibrin
Platelet activation
Proinflammatory effects
Anti-coagulant effects
CONTROL OF COAGULATION
Simple dilution: blood flows past the site of injury
washing out activated coagulation factors, which are
rapidly removed by the liver.
Most important counter-regulatory mechanisms
ASSOCIATED BLEEDING DISORDERS involve factors that are expressed by intact
Deficiencies of factors V, VII, VIII, IX, and X are endothelium adjacent to the site of injury.
associated with moderate to severe bleeding Fibrinolytic cascade
disorders largely accomplished through the enzymatic
Prothrombin deficiency is likely incompatible with activity of plasmin, which breaks down fibrin
life and interferes with its polymerization.
Factor XI deficiency is only associated with mild
bleeding
Individuals with factor XII deficiency do not bleed
and but may be susceptible to thrombosis.
TISSUE PLASMINOGEN ACTIVATOR
o tPA: Most important plasminogen activator o Stasis allows platelets and leukocytes to
o Synthesized principally by endothelium come into contact with the endothelium
o Most active when bound to fibrin when the flow is sluggish
o Useful therapeutic agent o Stasis also slows the washout of activated
o Fibrinolytic activity is largely confined to sites of clotting factors and impedes the inflow of
thrombosis clotting factor inhibitors
PROCOAGULANT/ANTICOAGULANT 3. HYPERCOAGULABLE STATES
• Abnormally high tendency of the blood to clot, and is
typically caused by alterations in coagulation factors.
• Primary (inherited) hypercoagulability: most often
caused by mutations in the factor V and prothrombin
genes
• Secondary (acquired) hypercoagulability:
THROMBOSIS, EMBOLISM AND INFARCTION
THROMBOSIS THROMBI
Virchow’s triad: Lines of Zahn - pale platelet and fibrin deposits
1. Endothelial injury alternating with darker red cell– rich layers.
2. Stasis or turbulent blood flow
3. Hypercoagulability of blood
MURAL THROMBI
thrombi occurring in heart chambers or aortic lumen
1. ENDOTHELIAL INJURY (arterial thrombotic)
• Can be produced by diverse exposures: physical
injury, infectious agents, abnormal blood flow,
inflammatory mediators, metabolic abnormalities
(hypercholesterolemia, homocystinemia) and toxins
absorbed from cigarette smoke.
• Major prothrombotic alterations:
- Procoagulant changes: downregulation of
ARTERIAL THROMBI
the expression of thrombomodulin à
frequently occlusive
sustained activation of thrombin,
rich in platelets
downregulation of other anticoagulants
- Anti-fibrinolytic effects: secretion of endothelial injury platelet activation
Plasminogen activator inhibitors (PAI) common sites: coronary > cerebral > femoral arteries
limits fibrinolysis and downregulates the
expression of tPA VENOUS THROMBI (PHLEBOTHROMBOSIS)
almost invariably occlusive
2. ABNORMAL BLOOD FLOW more red cells and few platelets
• Turbulence (chaotic blood flow) contributes to red or stasis thrombi
arterial and cardiac thrombosis by causing veins of lower extremities (90% of venous
endothelial injury or dysfunction, as well as by thrombosis)
forming countercurrents and local pockets of stasis
• Stasis and turbulence: POSTMORTEM CLOTS
o Both promote endothelial cell activation and gelatinous
enhanced procoagulant activity dark red portion lower portion
yellow “chicken fat” upper portion
usually not attached
AIR EMBOLISM
Gas bubbles within the circulation can coalesce and
FATE OF THROMBUS obstruct vascular flow and cause distal ischemic
Propagation - accumulate additional platelets and injury.
fibrin Decompression sickness - scuba divers, underwater
Embolization - dislodge & travel construction workers, and persons in unpressurized
Dissolution - fibrinolysis aircraft who undergo rapid ascent are at risk.
Organization and recanalization
AMNIOTIC FLUID EMBOLISM
EMBOLISM caused by infusion of amniotic fluid or fetal tissue
Embolus is detached intravascular solid, liquid or into the maternal circulation via a tear in placental
gaseous mass that is carried away from its point of membranes or rupture of uterine vein
origin to distant site activates the coagulation factors and components of
Emboli lodge in vessels too small to permit further innate immunity
passage, resulting in partial or complete vascular
occlusion
Primary consequence: ischemic necrosis (infarction)
of downstream tissues
INFARCTION
the obstruction of blood supply to an organ or region
of tissue, typically by a arterial thrombus or arterial
embolus, causing necrosis
Area of ischemic necrosis caused by occlusion of
either the arterial supply or venous drainage
WHITE INFARCTS
occur with arterial occlusions in solid organs with
end arterial circulation
PULMONARY EMBOLISM (most common form of embolic e.g. heart, spleen, kidney
diseasses)
originate from deep venous thromboses
Embolization in the pulmonary circulation leads to
hypoxia, hypotension, and right-sided heart failure.
RED INFARCTS
venous occlusion
in loose spongy tissues where blood can be collected
in the infarcted zone
in tissues with dual circulations
FAT AND MARROW EMBOLISM e.g. lungs and small intestines
common incidental findings after vigorous
cardiopulmonary resuscitation
symptomatic fat embolism syndrome: pulmonary
insufficiency, neurologic symptoms, anemia,
thrombocytopenia, and a diffuse petechial rash
HYPOVOLEMIC SHOCK
results from low cardiac output due to loss of blood
or plasma volume
e.g., resulting from hemorrhage or fluid loss from
severe burns
Clinical features: hypotension, a weak rapid pulse,
tachypnea, and cool, clammy, cyanotic skin.
SEPTIC SHOCK
ISCHEMIC COAGULATIVE NECROSIS Vasodilation and peripheral blood pooling caused by
main histologic finding associated with infarcts microbial infection
most are ultimately replaced by scar is frequently triggered by Gram - positive bacteria,
followed by Gram- negative and Fungi
associated with severe systemic inflammatory
response syndrome (SIRS).
the skin may be warm and flushed owing to periph-
eral vasodilation.
NEUROGENIC SHOCK
Loss of vascular tone
Peripheral pooling (anesthetic accident or spinal cord
injury)
ANAPHYLACTIC SHOCK
Systemic vasodilation
Increased vascular permeability
Ig-E mediated hypersensitivity
INFARCTION STAGES OF SHOCK
CNS infarction leads to liquefactive necrosis
SEPTIC INFARCTION
an area of necrosis resulting from vascular
obstruction by emboli composed of clumps of
bacteria or infected material
Infarct Abscess
SHOCK
state in which diminished cardiac output or reduced
effective circulating blood volume impairs tissue
perfusion and leads to hypoxia.
The primary threat to life is the underlying initiating
event (e.g., myocardial infarction, severe
hemorrhage, bacterial infection).
CARDIOGENIC SHOCK
results from low cardiac output due to outflow
obstruction or myocardial pump failure
e.g., myocardial infarction, arrythmia, tamponade
Clinical features: hypotension, a weak rapid pulse,
tachypnea, and cool, clammy, cyanotic skin.
