HEMODYNAMIC
DISORDERS
Jv = ([Pc − Pi] − σ[πc − πi])
•Hemodynamic
Disorders
•Thromboembolic
Disease
•Shock
Overview
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Edema (increased fluid in the ECF)
Hyperemia (INCREASED flow)
Congestion (INCREASED backup)
Hemorrhage (extravasation)
Hemostasis (opposite of thrombosis)
Thrombosis (clotting blood)
Embolism (downstream travel of a clot)
Infarction (death of tissues w/o blood)
Shock (circulatory failure/collapse)
EDEMA
• ONLY 4 POSSIBILITIES!!!
–Increased Hydrostatic Pressure
–Reduced Oncotic Pressure
–Lymphatic Obstruction
–Sodium/Water Retention
WATER
• 60% of body
• 2/3 of body water is INTRA-cellular
• The rest is INTERSTITIAL
• Only 5% is INTRA-vascular
• EDEMA is SHIFT to the INTERSTITIAL
SPACE
• HYDRO– -THORAX, -PERICARDIUM, -PERITONEAL
• EFFUSIONS, ASCITES, ANASARCA
INCREASED HYDROSTATIC
PRESSURE
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Impaired venous return
Congestive heart failure
Constrictive pericarditis
Ascites (liver cirrhosis)
Venous obstruction or compression
Thrombosis
External pressure (e.g., mass)
Lower extremity inactivity with prolonged dependency
Arteriolar dilation
Heat
Neurohumoral dysregulation
REDUCED PLASMA ONCOTIC
PRESSURE (HYPOPROTEINEMIA)
• Protein-losing glomerulopathies
(nephrotic syndrome)
• Liver cirrhosis (ascites)
• Malnutrition
• Protein-losing gastroenteropathy
LYMPHATIC OBSTRUCTION
(LYMPHEDEMA)
• Inflammatory
• Neoplastic
• Postsurgical
• Postirradiation
Na+ RETENTION
• Excessive salt intake with renal
insufficiency
• Increased tubular reabsorption of
sodium
• Renal hypoperfusion
Increased renin-angiotensinaldosterone secretion
INFLAMMATION
• Acute inflammation
• Chronic inflammation
• Angiogenesis
Jv = ([Pc − Pi] − σ[πc − πi])
CHF EDEMA
• INCREASED VENOUS PRESSURE
DUE TO FAILURE
• DECREASED RENAL PERFUSION,
triggering of RENINANGIOTENSION-ALDOSTERONE
complex, resulting ultimately in
SODIUM RETENTION
HEPATIC ASCITES
• PORTAL HYPERTENSION
• HYPOALBUMINEMIA
ASCITES
RENAL EDEMA
• SODIUM RETENTION
• PROTEIN LOSING
GLOMERULOPATHIES
(NEPHROTIC SYNDROME)
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EDEMA
SUBCUTANEOUS (“PITTING”)
“DEPENDENT”
ANASARCA
LEFT vs RIGHT HEART
PERIORBITAL
PULMONARY
CEREBRAL (closed cavity, no expansion)
– HERNIATION of cerebellar tonsils
– HERNIATION of hippocampal uncus over tentorium
– HERNIATION, subfalcine
“Pitting” Edema
Transudate vs Exudate
• Transudate
– results from disturbance of Starling forces
– specific gravity < 1.012
– protein content < 3 g/dl,
LDH LOW
• Exudate
– results from damage to the capillary wall
– specific gravity > 1.012
– protein content > 3 g/dl,
LDH HIGH
HYPEREMIA/(CONGESTION)
HYPEREMIA
Active Process
CONGESTION
Passive Process
Acute or Chronic
CONGESTION
• LUNG
–ACUTE
–CHRONIC
• LIVER
–ACUTE
–CHRONIC
• CEREBRAL
ACUTE PASSIVE
HYPEREMIA/CONGESTION,
LUNG

Kerley B
Air
Bronchogram
CHRONIC PASSIVE
HYPEREMIA/CONGESTION,
LUNG
Acute Passive Congestion,
Liver
Acute Passive Congestion,
Liver
CHRONIC PASSIVE
HYPEREMIA/CONGESTION, LIVER
HEMORRHAGE
• EXTRAVASATION beyond vessel
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“HEMORRHAGIC DIATHESIS”
HEMATOMA (implies MASS effect)
“DISSECTION”
PETECHIAE (1-2mm) (PLATELETS)
PURPURA <1cm
ECCHYMOSES >1cm (BRUISE)
HEMO-: -thorax, -pericardium, -peritoneum, HEMARTHROSIS
• ACUTE, CHRONIC
EVOLUTION of HEMORRHAGE
• ACUTE CHRONIC
• PURPLE GREEN BROWN
• HGB BILIRUBIN HEMOSIDERIN
HEMATOMA
vs.
“CLOT”
HEMOSTASIS
• OPPOSITE of THROMBOSIS
–PRESERVE LIQUIDITY OF BLOOD
–“PLUG” sites of vascular injury
• THREE COMPONENTS
–VASCULAR WALL, i.e., endoth/ECM
–PLATELETS
–COAGULATION CASCADE
SEQUENCE of EVENTS
following VASCULAR INJURY
• ARTERIOLAR VASOCONSTRICTION
– Reflex Neurogenic
– Endothelin, from endothelial cells
• THROMBOGENIC ECM at injury site
– Adhere and activate platelets
– Platelet aggregation (1˚ HEMOSTASIS)
• TISSUE FACTOR released by endothelium, plats.
– Activates coagulation cascadethrombinfibrin (2˚
HEMOSTASIS)
• FIBRIN polymerizes, TPA limits plug
PLAYERS
•ENDOTHELIUM
•PLATELETS
•COAGULATION
“CASCADE”
ENDOTHELIUM
• NORMALLY
–ANTIPLATELET PROPERTIES
–ANTICOAGULANT PROPERTIES
–FIBRINOLYTIC PROPERTIES
• IN INJURY
–PRO-COAGULANT PROPERTIES
ENDOTHELIUM
• ANTI-Platelet PROPERTIES
– Protection from the subendothelial ECM
– Degrades ADP (inhib. Aggregation)
• ANTI-Coagulant PROPERTIES
– Membrane HEPARIN-like molecules
– Makes THROMBOMODULIN Protein-C
– TISSUE FACTOR PATHWAY INHIBITOR
• FIBRINOLYTIC PROPERTIES (TPA)
ENDOTHELIUM
• PROTHROMBOTIC PROPERTIES
–Makes vWF, which binds PlatsColl
–Makes TISSUE FACTOR (with plats)
–Makes Plasminogen inhibitors
ENDOTHELIUM
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ACTIVATED by INFECTIOUS AGENTS
ACTIVATED by HEMODYNAMICS
ACTIVATED by PLASMA
ACTIVATED by ANYTHING which
disrupts it
PLATELETS
• ALPHA GRANULES
– Fibrinogen
– Fibronectin
– Factor-V, Factor-VIII
– Platelet factor 4, TGF-beta
• DELTA GRANULES (DENSE BODIES)
– ADP/ATP, Ca+, Histamine, Serotonin, Epineph.
• With endothelium, form TISSUE FACTOR
NORMAL platelet on LEFT, “DEGRANULATING” ALPHA
GRANULE ON RIGHT AT OPEN WHITE ARROW
PLATELET PHASES
• ADHESION
• SECRETION (i.e.,
“release” or “activation”
or “degranulation”)
• AGGREGATION
PLATELET ADHESION
• Primarily to the
subendothelial ECM
• Regulated by vWF, which
bridges platelet surface
receptors to ECM collagen
PLATELET SECRETION
• BOTH granules, α and δ
• Binding of agonists to
platelet surface receptors
AND intracellular protein
PHOSPHORYLATION
PLATELET AGGREGATION
• ADP
• TxA2 (Thromboxane A2)
• THROMBIN from coagulation
cascade also
• FIBRIN further strengthens
and hardens and contracts the
platelet plug
PLATELET EVENTS
• ADHERENCE to ECM
• SECRETION of ADP and TxA2
• EXPOSE phospholipid
complexes
• Express TISSUE FACTOR
• PRIMARYSECONDARY PLUG
• STRENGTHENED by FIBRIN
COAGULATION “CASCADE”
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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, Z
COAGULATION TESTS
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(a)PTT
INTRINSIC
(HEP Rx)
PT (INR) EXTRINSIC (COUM Rx)
BLEEDING TIME (PLATS) (2-9min)
Platelet count (150,000-400,000/mm3)
Fibrinogen
Factor assays
THROMBOSIS
• Pathogenesis
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Endothelial Injury
Alterations in Flow
Hypercoagulability
Morphology
Fate
Clinical Correlations
Venous
Arterial (Mural)
THROMBOSIS
• Virchow’s TRIANGLE
ENDOTHELIAL
INJURY
ABNORMAL FLOW
(NON-LAMINAR)
HYPERCOAGULATION
ENDOTHELIAL “INJURY”
• Jekyll/Hyde disruption
–any perturbation in the dynamic
balance of the pro- and
antithrombotic effects of
endothelium, not only physical
“damage”
ENDOTHELIUM
• ANTI-Platelet PROPERTIES
– Protection from the subendothelial ECM
– Degrades ADP (inhib. Aggregation)
• ANTI-Coagulant PROPERTIES
– Membrane HEPARIN-like molecules
– Makes THROMBOMODULIN Protein-C
– TISSUE FACTOR PATHWAY INHIBITOR
• FIBRINOLYTIC PROPERTIES (TPA)
ENDOTHELIUM
• PROTHROMBOTIC PROPERTIES
–Makes vWF, which binds PlatsColl
–Makes TISSUE FACTOR (with plats)
–Makes Plasminogen inhibitors
ABNORMAL FLOW
• NON-LAMINAR FLOW
• TURBULENCE
• EDDIES
• STASIS
• “DISRUPTED” ENDOTHELIUM
ALL of these factors may bring
platelets into contact with
endothelium and/or ECF
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1 HYPERCOAGULABILITY
(INHERITED)
• COMMONEST: Factor V and
Prothrombin defects
• Common: Mutation in prothrombin gene,
Mutation in methylenetetrahydrofolate gene
• Rare: Antithrombin III deficiency, Protein C
deficiency, Protein S deficiency
• Very rare: Fibrinolysis defects
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2 HYPERCOAGULABILITY
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(ACQUIRED)
Prolonged bed rest or immobilization
Myocardial infarction
Atrial fibrillation
Tissue damage (surgery, fracture, burns)
Cancer (TROUSSEAU syndrome, i.e., migratory thrombophlebitis)
Prosthetic cardiac valves
Disseminated intravascular coagulation
Heparin-induced thrombocytopenia
Antiphospholipid antibody syndrome (lupus anticoagulant syndrome)
• Lower risk for thrombosis:
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Cardiomyopathy
Nephrotic syndrome
Hyperestrogenic states (pregnancy)
Oral contraceptive use
Sickle cell anemia
Smoking, Obesity
MORPHOLOGY
• ADHERENCE TO VESSEL WALL
– HEART (MURAL)
– ARTERY (OCCLUSIVE/INFARCT)
– VEIN
• OBSTRUCTIVE vs. NON-OBSTRUCTIVE
• RED, YELLOW, GREY/WHITE
• ACUTE, ORGANIZING, OLD
MURAL THROMBI, HEART
FATE of THROMBI
• PROPAGATION (Downstream)
• EMBOLIZATION
• DISSOLUTION
• ORGANIZATION
• RECANALIZATION
OCCLUSIVE ARTERIAL THROMBUS
D.V.T.
• D. (CALF, THIGH, PELVIC) V.T.
• CHF a huge factor
• INACTIVITY!!!
• Trauma
• Surgery
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Burns
Injury to vessels,
Procoagulant substances from tissues
Reduced t-PA activity
ARTERIAL/CARDIAC THROMBI
• ACUTE MYOCARDIAL INFARCTION =
OLD ATHEROSCLEROSIS + FRESH
THROMBOSIS
• ARTERIAL THROMBI also may send
fragments DOWNSTREAM, but these
fragments may contain flecks of
calcified or cholesterol PLAQUE also
• LODGING is PROPORTIONAL to the %
of cardiac output the organ receives,
i.e., brain, kidneys, spleen, legs, or the
diameter of the downstream vessel
ATHEROEMBOLI
• “CHOLESTEROL” clefts are
components of atherosclerotic
arterial plaques, NOT venous
thrombi!!!
Disseminated Intravascular Coagulation
D.I.C.
• OBSTETRIC COMPLICATIONS
• ADVANCED MALIGNANCY
• SHOCK
(Shock and DIC are joined at the hip)
NOT a primary disease
CONSUMPTIVE coagulopathy, e.g., reduced
platelets, fibrinogen, F-VIII and other
consumable clotting factors, brain, heart,
lungs, kidneys, MICROSCOPIC ONLY
EMBOLISM
•Pulmonary
• Systemic (Mural Thrombi and
Aneurysms)
• Fat
• Air
• Amniotic Fluid
PULMONARY EMBOLISM
• USUALLY SILENT, USUALLY SILENT
• CHEST PAIN, LOW PO2, S.O.B.
• Sudden OCCLUSION of >60% of
pulmonary vasculature, presents a HIGH
risk for sudden death, i.e., acute cor
pulmonale, ACUTE right heart failure
• “SADDLE” embolism often/usually fatal
• PRE vs. POST mortem blood clot:
– PRE: Friable, adherent, lines of “ZAHN”
– POST: Current jelly or chicken fat
SYSTEMIC EMBOLI
• “PARADOXICAL” EMBOLI
• 80% cardiac/20% aortic
• Embolization lodging site is
proportional to the degree of flow
(cardiac output) that area or organ
gets, i.e., brain (15%), kidneys
(~25%), legs, splanchnic (~25%),
liver (~25%)
OTHER EMBOLI
•FAT (long bone fx’s, also
bones with marrow)
•AIR (SCUBA “bends”)
•AMNIOTIC FLUID,
very prolonged or difficult
delivery, high mortality
Amniotic Fluid Embolism
INFARCTION
• Defined as an area of necrosis*
secondary to decreased blood
flow
• HEMORRHAGIC vs. ANEMIC
• RED vs. WHITE
– END ARTERIES vs. DUAL ARTERY
SUPPLY
• ACUTEORGANIZATIONFIBROSIS
INFARCTION FACTORS
• NATURE of VASCULAR SUPPLY
– Single end arteries such as kidney, spleen?
– Dual blood supply such as lung, liver?
• RATE of DEVELOPMENT
–SLOW (BETTER)
–FAST (WORSE)
• VULNERABILITY to HYPOXIA
–MYOCYTE vs. FIBROBLAST
• CHF vs. NO CHF
HEART
SHOCK
• Pathogenesis
–Cardiac
–Septic
–Hypovolemic
• Morphology
• Clinical Course
SHOCK
• Definition: CARDIOVASCULAR COLLAPSE
• Common pathophysiologic features:
– INADEQUATE CARDIAC OUTPUT and/or
– INADEQUATE BLOOD VOLUME
GENERAL RESULTS
• INADEQUATE TISSUE PERFUSION
• CELLULAR HYPOXIA
• If UN-corrected, a FATAL outcome
TYPES of SHOCK
• CARDIOGENIC: (Acute, Chronic Heart
Failure)
• HYPOVOLEMIC: (Hemorrhage or
Leakage)
• SEPTIC: (“ENDOTOXIC” shock, #1 killer in
ICU)
• NEUROGENIC: (loss of vascular tone)
• ANAPHYLACTIC: (IgE mediated systemic vasodilation and increased
vascular permeability)
CARDIOGENIC shock
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MI
VENTRICULAR RUPTURE
ARRHYTHMIA
CARDIAC TAMPONADE
PULMONARY EMBOLISM (acute RIGHT
heart failure or “cor pulmonale”)
HYPOVOLEMIC shock
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HEMORRHAGE, Vasc. compartmentH2O
VOMITING, Vasc. compartmentH2O
DIARRHEA, Vasc. compartmentH2O
BURNS, Vasc. compartmentH2O
SEPTIC shock
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OVERWHELMING INFECTION
“ENDOTOXINS”, i.e., LPS (Usually Gm-)
Gm+
FUNGAL
“SUPERANTIGENS”, (Superantigens are polyclonal
T-lymphocyte activators that induce systemic inflammatory
cytokine cascades similar to those occurring downstream
in septic shock, “toxic shock” superantigens by staph are
the prime example.)
SEPTIC shock events*
(overwhelming infection)
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Peripheral vasodilation
Pooling
Endothelial Activation
DIC
* Think of this as a TOTAL BODY
inflammatory response, or early
total body infarct!
ENDOTOXINS
• Usually Gm• Degraded bacterial cell wall products
• Also called “LPS”, because they are Lipo-
Poly-Saccharides
• Attach to a cell surface antigen known as
CD-14
ENDOTOXINS
SEPTIC shock events
(linear sequence)
• SYSTEMIC VASODILATION (hypotension)
• ↓ MYOCARDIAL CONTRACTILITY
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DIFFUSE ENDOTHELIAL ACTIVATION
LEUKOCYTE ADHESION
ALVEOLAR DAMAGE (ARDS)
DIC
VITAL ORGAN FAILURE CNS
CLINICAL STAGES of shock
•NON-PROGRESSIVE
(compensatory mechanisms)
•PROGRESSIVE
(acidosis, early organ failure)
•IRREVERSIBLE
NON-PROGRESSIVE
• COMPENSATORY MECHANISMS
•CATECHOLAMINES
• VITAL ORGANS PERFUSED
PROGRESSIVE
• HYPOPERFUSION
• EARLY “VITAL” ORGAN FAILURE
• OLIGURIA
•ACIDOSIS
IRREVERSIBLE
•HEMODYNAMIC
CORRECTIONS
of no use
PATHOLOGY
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MULTIPLE ORGAN FAILURE
SUBENDOCARDIAL HEMORRHAGE (why?)
ACUTE TUBULAR NECROSIS (why?)
DAD (Diffuse Alveolar Damage, lung) (why?)
GI MUCOSAL HEMORRHAGES (why?)
LIVER NECROSIS (why?)
DIC (why?)
ARDS/DAD
MYOCARDIAL NECROSIS
ATN
DIC
CLINICAL PROGRESSION
of SYMPTOMS
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Hypotension 
Tachycardia 
Tachypnea 
Warm skin Cool skin Cyanosis
Renal insufficiency
Obtundance
Death