Hemodynamic Disorders,

Thromboembolism, and Shock

LMGP
Cell & tissue health
▶ intact circulation to deliver oxygen and remove wastes
▶ normal fluid homeostasis
▶ maintained vessel wall integrity, intravascular pressure and
osmolarity
▶ EDEMA (water extravasation into interstitial spaces )
▶ maintaining blood as a liquid until clot formation is needed
▶ HEMORRHAGE - absence of clotting after vascular injury results
▶ THROMBOSIS – inappropriate clotting → hypotension (shock)
▶ EMBOLISM - migration of clots
EDEMA & EFFUSIONS

▶ increased fluid in tissue (edema) or

body cavities (effusions)
▶ Fluid in body cavities: hydrothorax,
hydropericardium, or
hydroperitoneum (ascites)

Anasarca is a severe and generalized TWO TYPES:

edema with profound subcutaneous 1. Inflammatory (exudate)
tissue swelling. 2. Non-inflammatory (transudate)
Non- inflammatory Edema
Variables affecting fluid transit
across capillary walls
1. Increased hydrostatic pressure
2. Decreased plasma osmotic
pressure
3. Lymphatic obstruction
4. Sodium retention
EDEMA & EFFUSIONS

INCREASED HYDROSTATIC
PRESSURE
1. Localized - impaired
venous return
2. Generalized→ systemic
edema - congestive heart
EDEMA & EFFUSIONS

REDUCED PLASMA OSMOTIC PRESSURE

▶ Hypoalbuminuria – common cause
▶ nephrotic syndrome
▶ Severe liver disease
▶ Protein malnutrition
LYMPHATIC OBSTRUCTION (LYMPHEDEMA)
▶ inflammatory or neoplastic condition
▶ Eg. Filariasis, breast cancer (peau d’orange), therapy - axillary
lymph node resection
EDEMA & EFFUSIONS

SODIUM AND WATER RETENTION

▶ ↑ hydrostatic pressure , ↓plasma osmotic
pressure
Renal diseases:
▶ poststreptococcal glomerulonephritis
▶ acute renal failure
EDEMA & EFFUSIONS
MORPHOLOGY
▶ Gross inspection – seen easily
▶ Microscopically - clearing and separation of the
extracellular matrix elements
1. Subcutaneous edema – in areas farthest from the heart
▶ Dependent edema - legs, sacrum
▶ Pitting edema - finger-shaped depression upon finger pressure
▶ Periorbital edema – eyelids (renal dysfunction)
2. Pulmonary edema
▶ Lungs 2x weight, frothy blood-tinged fluid (sections)
3. Brain edema
▶ Localized/ generalized
EDEMA & EFFUSIONS

CLINICAL CORRELATIONS
1. Subcutaneous edema
▶ signals potential underlying cardiac or renal disease
▶ impair wound healing or the clearance of infections
2. Pulmonary edema
▶ left ventricular failure,renal failure, acute respiratory distress
syndrome, inflammatory and infectious disorders of the lung
▶ interferes normal ventilator, impedes oxygen diffusion, creates a
favorable environment for infections
3. Brain edema
▶ brain can herniate, ↑ intracranial pressure → death
HYPEREMIA AND CONGESTION
increase in blood volume within a tissue

HYPEREMIA CONGESTION
▶ Active process ▶ Passive process

▶ arteriolar dilation and ▶ impaired outflow of

increased blood inflow venous blood from a tissue
▶ Systemic: cardiac failure;
▶ Local: sites of
Local: venous obstruction
inflammation or in
exercising skeletal muscle
▶ Erythema- ↑ oxygenated ▶ Cyanosis - ↑ deoxygenated
blood blood
HYPEREMIA AND CONGESTION
HEMORRHAGE
extravasation of blood from vessels

MANIFESTATION & CONSEQUENCES

1. Hematoma – hemorrhage w/in tissue
▶ Body cavities - hemothorax, hemopericardium, hemoperitoneum, or
hemarthrosis
2. Petechia - minute (1 to 2 mm) hemorrhages into skin, mucous
membranes, or serosal surfaces
▶ thrombocytopenia, defective platelet function, vitamin C deficiency
3. Purpura - larger (3 to 5 mm) hemorrhages
4. Ecchymoses - larger (1 to 2 cm) subcutaneous hematomas
▶ Color change: Hg (red-blue) →biliverdin (blue green) →hemosiderin
(golden-brown)
HEMORRHAGE

Factors for hemorrhage significance:

1. Volume of blood loss, rate of bleeding
▶ hemorrhagic (hypovolemic) shock - ↑ vol loss
2. Site
▶ Brain → death
3. Frequency
▶ Chronic/ recurrent → IDA
HEMOSTASIS AND THROMBOSIS
NORMAL HEMOSTASIS
▶ regulated processes that maintain blood in a fluid, clot-free state
▶ rapidly forms a localized hemostatic plug at the site of vascular injury
 HEMOSTASIS AND THROMBOSIS

THROMBOSIS
▶ the formation of blood clot (thrombus) within
intact vessels
3 primary influences on thrombus formation
(called Virchow's triad):
▶ (1) endothelial injury, (Alteration in wall)
▶ (2) stasis or turbulence of blood flow (Alteration in
flow)
▶ (3) blood hypercoagulability (Alteration in
cougulability)
HEMOSTASIS AND THROMBOSIS

1.ENDOTHELIAL INJURY
▶ Prevents platelet adhesion or dilutes coagulation factors,
↑ procoagulant factors, ↓ anticoagulant molecules
▶ Causes: hypertension, turbulent blood flow, bacterial
products, radiation injury, metabolic abnormalities such
as homocystinuria and hypercholesterolemia, and toxins
absorbed from cigarette smoke.
▶ Examples:
▶ formation of thrombi in the cardiac chambers after MI
▶ plaques in atherosclerotic arteries
 HEMOSTASIS AND THROMBOSIS

ABNORMAL BLOOD FLOW

▶ Turbulence & Stasis - (chaotic) blood flow
Effects:
1. promote endothelial cell activation and enhanced
procoagulant activity
2. allows platelets and leukocytes to come into contact with
the endothelium
3. slows the washout of activated clotting factors and
impedes the inflow of clotting factor inhibitors
▶ Ulcerated atherosclerotic plaques, aneurysms, MI,
Hyperviscosity syndromes
HEMOSTASIS AND THROMBOSIS
HYPERCOAGULABILITY
▶ alteration of the coagulation pathways → thrombosis
1. Primary/inherited
▶ Factor V/ Leiden mutation - alters an amino acid residue and
renders it resistant to protein C
▶ prothrombin genes mutation - G to A nucleotide substitution; ↑ PT
▶ Deficiencies in antithrombin III, protein C, or protein S
2. Secondary/ Acquired
▶ Heparin­induced thrombocytopenic (HIT) syndrome - development
of autoantibodies binding heparin and platelet membrane protein
▶ Antiphospholipid antibody syndrome - autoantibodies directed
against anionic phospholipids
HEMOSTASIS AND THROMBOSIS
MORPHOLOGY

▶ lines of Zahn - pale platelet and fibrin layers alternating

with darker red cell–rich layers; distinguish antemortem
thrombosis from the bland nonlaminated postmortem clots

▶ Mural thrombi - heart chambers or in the aortic lumen

▶ frequently occlusive; produced by platelet and coagulation
activation; friable meshwork of platelets, fibrin, erythrocytes, and
degenerating leukocytes.
HEMOSTASIS AND THROMBOSIS

MORPHOLOGY

▶ Phlebothrombosis - Venous thrombosis

▶ invariably occlusive, result of activation of the coagulation
cascade, and platelets play a secondary role.
▶ Aka red, or stasis, thrombi - contain more enmeshed erythrocytes

▶ Vegetations - heart valves

▶ infective endocarditis - Bacterial or fungal blood-borne infections;
large thrombotic masses
▶ nonbacterial thrombotic endocarditis - Sterile vegetations in
hypercoagulable states
HEMOSTASIS AND THROMBOSIS

FATE OF THROMBUS

▶ Propagation: thrombus enlarge, accumulation of

additional platelets and fibrin
▶ Embolization: Thrombi dislodge or fragment and are
transported elsewhere in the vasculature.
▶ Dissolution: Thrombi are removed by fibrinolytic activity.
▶ Organization: Thrombi induce inflammation and fibrosis
▶ Recanalization: re-establishing some degree of flow
EMBOLISM

▶ intravascular solid, liquid, or gaseous mass that is carried

by the blood to a site distant from its point of origin

Forms:
▶ Thromboembolism – dislodged thrombus
▶ Others: fat droplets, bubbles of air , atherosclerotic
debris (cholesterol emboli), tumor fragments, bits of bone
marrow, or foreign bodies (bullets)
EMBOLISM
PULMONARY THROMBOEMBOLISM
▶ Origin: deep leg vein thrombi above the level of the knee
▶ Site: main pulmonary artery, saddle embolus – branch of
right and left pulmonary arterie, arteriole
Clinical and pathologic features:
▶ small and clinically silent → organization
▶ large embolus in major pulmonary artery → death
▶ medium-sized arteries and subsequent rupture of capillaries →
pulmonary hemorrhage
▶ small end-arteriolar pulmonary branches → infarction
▶ Multiple emboli → pulmonary hypertension and right
ventricular failure (cor pulmonale)
EMBOLISM

SYSTEMIC THROMBOEMBOLISM
▶ Origin: cardiac mural or valvular thrombi, aortic
aneurysms, or atherosclerotic plaques, unknown origin
▶ Venous emboli → lungs
▶ Arterial emboli → lower extremities, CNS, intestines,
kidneys, and spleen

*whether an embolus causes tissue infarction depends on the

site of embolization and the presence or absence of
collateral circulation
INFARCTION

▶ Infarcts are areas of ischemic necrosis.

Cause:
▶ arterial occlusion (typically due to thrombosis or embolization)
▶ venous outflow obstruction

MORPHOLOGY
1. hemorrhagic (red) - venous occlusion or occurring in spongy tissues
2. pale/anemic (white) - arterial occlusion in compact tissues
INFARCTION

FACTORS THAT INFLUENCE INFARCT DEVELOPMENT

1. Anatomy of the vascular supply
▶ presence or absence of an alternative blood supply
▶ Lungs, liver, hand & forearm – dual supply, resistant to infarction
▶ Kidney, spleen - end-arterial circulation, vulnerable to infarction
2. Rate of occlusion
▶ slow occlusion → less likely to cause infarction, allow time for the
development of collateral blood supplies
▶ Coronary artery - interarteriolar anastomoses (interconnect the
three major coronary arteries)
INFARCTION

FACTORS THAT INFLUENCE INFARCT DEVELOPMENT

3. Tissue vulnerability to ischemia
▶ Neurons – irreversible damage, 3 to 4 minutes
▶ Myocardial cells – die 20 to 30 minutes
▶ Fibroblast in myocardium - viable after many hours
4. Hypoxemia
▶ abnormally low blood O2 content, increase risk of infarction
SHOCK
▶ state of systemic tissue hypoperfusion due to reduced
cardiac output and/or reduced effective circulating blood
volume
Forms:
1. Cardiogenic shock - low cardiac output due to myocardial
pump failure
2. Hypovolemic shock - low cardiac output due to loss of
blood or plasma volume
3. Shock associated w/ systemic inflammation – massive
outpouring of inflammatory mediators from innate and
adaptive immune cells producing arterial vasodilation,
vascular leakage & venous blood pooling;
microbial/non-microbial
Thank You! ☺