1. HEMODYNAMIC
DISORDERS
Jv = ([Pc − Pi] − σ[πc − πi])

2. •Hemodynamic
Disorders
•Thromboembolic
Disease
•Shock

3. Overview
• Edema
• Hyperemia
• Congestion
• Hemorrhage
• Hemostasis
• Thrombosis
• Embolism
• Infarction
• Shock

4. EDEMA
• ONLY 4 POSSIBILITIES!!!
–Increased Hydrostatic Pressure
–Reduced Oncotic Pressure
–Lymphatic Obstruction
–Sodium/Water Retention

5. 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, -PERICARDIUM
• EFFUSIONS, ASCITES, ANASARCA

6. INCREASED HYDROSTATIC
PRESSURE
• 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

7. REDUCED PLASMA ONCOTIC
PRESSURE (HYPOPROTEINEMIA)
• Protein-losing glomerulopathies
(nephrotic syndrome)
• Liver cirrhosis (ascites)
• Malnutrition
• Protein-losing gastroenteropathy

8. LYMPHATIC OBSTRUCTION
(LYMPHEDEMA)
• Inflammatory
• Neoplastic
• Postsurgical
• Postirradiation

9. Na+ RETENTION
• Excessive salt intake with renal
insufficiency
• Increased tubular reabsorption of
sodium

• Renal hypoperfusion
Increased
renin-angiotensin-aldosterone
secretion

10. INFLAMMATION
• Acute inflammation
• Chronic inflammation
• Angiogenesis

11. Jv = ([Pc − Pi] − σ[πc − πi])

12. CHF EDEMA
• INCREASED VENOUS PRESSURE
DUE TO FAILURE
• DECREASED RENAL PERFUSION,
triggering of RENIN-ANGIOTENSION-
ALDOSTERONE
complex, resulting ultimately in
SODIUM RETENTION

13. HEPATIC ASCITES
• PORTAL HYPERTENSION
• HYPOALBUMINEMIA

14. ASCITES

15. RENAL EDEMA
• SODIUM RETENTION
• PROTEIN LOSING
GLOMERULOPATHIES
(NEPHROTIC SYNDROME)

16. EDEMA
• SUBCUTANEOUS (“PITTING”)
• “DEPENDENT”
• ANASARCA
• LEFT vs. RIGHT HEART
• PERIORBITAL (RENAL)
• PULMONARY
• CEREBRAL (closed cavity, no expansion)
– HERNIATION of cerebellar tonsils
– HERNIATION of hippocampal uncus over tentorium
– HERNIATION, subfalcine

17. “Pitting” Edema

18. Transudate vs Exudate
• Transudate
– results from disturbance of Starling forces
– specific gravity < 1.012
– protein content < 3 g/dl
• Exudate
– results from damage to the capillary wall
– specific gravity > 1.012
– protein content > 3 g/dl

19. HYPEREMIA/(CONGESTION)

20. HYPEREMIA
Active Process
CONGESTION
Passive Process
Acute or Chronic

21. CONGESTION
• LUNG
–ACUTE
–CHRONIC
• LIVER
–ACUTE
–CHRONIC
• CEREBRAL

22. ACUTE PASSIVE
HYPEREMIA/CONGESTION,
LUNG


23. Kerley B
Air
Bronch-ogram

26. CHRONIC PASSIVE
HYPEREMIA/CONGESTION,
LUNG

27. Acute Passive Congestion,
Liver

28. Acute Passive Congestion,
Liver

29. CHRONIC PASSIVE
HYPEREMIA/CONGESTION, LIVER

32. HEMORRHAGE
• EXTRAVASATION beyond vessel
• “HEMORRHAGIC DIATHESIS”
• HEMATOMA (implies MASS effect)
• “DISSECTION”
• PETECHIAE (1-2mm) (PLATELETS)
• PURPURA <1cm
• ECCHYMOSES >1cm (BRUISE)
• HEMO-: -thorax, -pericardium, -peritoneum, HEMARTHROSIS
• ACUTE, CHRONIC

33. EVOLUTION of HEMORRHAGE
• ACUTE CHRONIC
• PURPLE GREEN BROWN
• HGB BILIRUBIN HEMOSIDERIN

39. HEMATOMA
vs.
“CLOT”

40. HEMOSTASIS
• OPPOSITE of THROMBOSIS
–PRESERVE LIQUIDITY OF BLOOD
–“PLUG” sites of vascular injury
• THREE COMPONENTS
–VASCULAR WALL, i.e., endoth/ECM
–PLATELETS
–COAGULATION CASCADE

41. 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
– Activates coagulation cascadethrombinfibrin (2˚
HEMOSTASIS)
• FIBRIN polymerizes, TPA limits plug

42. PLAYERS
•ENDOTHELIUM
•PLATELETS
•COAGULATION
“CASCADE”

43. ENDOTHELIUM
• NORMALLY
–ANTIPLATELET PROPERTIES
–ANTICOAGULANT PROPERTIES
–FIBRINOLYTIC PROPERTIES
• IN INJURY
–PRO-COAGULANT PROPERTIES

45. 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)

46. ENDOTHELIUM
• PROTHROMBOTIC PROPERTIES
–Makes vWF, which binds PlatsColl
–Makes TISSUE FACTOR (with plats)
–Makes Plasminogen inhibitors

47. ENDOTHELIUM
• ACTIVATED by INFECTIOUS AGENTS
• ACTIVATED by HEMODYNAMICS
• ACTIVATED by PLASMA

48. 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

50. NORMAL platelet on LEFT, “DEGRANULATING” ALPHA
GRANULE ON RIGHT AT OPEN WHITE ARROW

52. PLATELET PHASES
• ADHESION
• SECRETION (i.e.,
“release” or “activation”
or “degranulation”)
• AGGREGATION

53. PLATELET ADHESION
• Primarily to the
subendothelial ECM
• Regulated by vWF, which
bridges platelet surface
receptors to ECM collagen

54. PLATELET SECRETION
• BOTH granules, α and δ
• Binding of agonists to
platelet surface receptors
AND intracellular protein
PHOSPHORYLATION

55. PLATELET AGGREGATION
• ADP
• TxA2 (Thromboxane A2)
• THROMBIN from coagulation
cascade also
• FIBRIN further strengthens
and hardens and contracts the
platelet plug

56. PLATELET EVENTS
• ADHERENCE to ECM
• SECRETION of ADP and TxA2
• EXPOSE phospholipid
complexes
• Express TISSUE FACTOR
• PRIMARYSECONDARY PLUG
• STRENGTHENED by FIBRIN

57. 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, Z

59. COAGULATION TESTS
• (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

60. THROMBOSIS
• Pathogenesis
• Endothelial Injury
• Alterations in Flow
• Hypercoagulability
• Morphology
• Fate
• Clinical Correlations
• Venous
• Arterial (Mural)

61. THROMBOSIS
• Virchow’s TRIANGLE
ENDOTHELIAL
INJURY
ABNORMAL FLOW
(NON-LAMINAR)
HYPER-COAGULATION

62. ENDOTHELIAL “INJURY”
• Jekyll/Hyde disruption
–any perturbation in the dynamic
balance of the pro- and
antithrombotic effects of
endothelium, not only physical
“damage”

63. 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)

64. ENDOTHELIUM
• PROTHROMBOTIC PROPERTIES
–Makes vWF, which binds PlatsColl
–Makes TISSUE FACTOR (with plats)
–Makes Plasminogen inhibitors

65. ABNORMAL FLOW
•NON-LAMINAR FLOW
• TURBULENCE
• EDDIES
• STASIS
• “DISRUPTED” ENDOTHELIUM
ALL of these factors may bring
platelets into contact with
endothelium and/or ECF

66. 1˚ HYPERCOAGULABILITY
(INHERITED)
• COMMONEST: Factor V and
Prothrombin defects
• Common: Mutation in prothrombin gene,
Mutation in methyltetrahydrofolate gene
• Rare: Antithrombin III deficiency, Protein C
deficiency, Protein S deficiency
• Very rare: Fibrinolysis defects

68. 2˚ HYPERCOAGULABILITY
(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:
– Cardiomyopathy
– Nephrotic syndrome
– Hyperestrogenic states (pregnancy)
– Oral contraceptive use
– Sickle cell anemia
– Smoking, Obesity

69. MORPHOLOGY
• ADHERENCE TO VESSEL WALL
–HEART (MURAL)
–ARTERY (OCCLUSIVE/INFARCT)
– VEIN
• OBSTRUCTIVE vs. NON-OBSTRUCTIVE
• RED, YELLOW, GREY/WHITE
• ACUTE, ORGANIZING, OLD

70. MURAL THROMBI, HEART

71. FATE of THROMBI
• PROPAGATION (Downstream)
• EMBOLIZATION
• DISSOLUTION
• ORGANIZATION
• RECANALIZATION

73. OCCLUSIVE ARTERIAL THROMBUS

74. D.V.T. • D. (CALF, THIGH, PELVIC) V.T.
• CHF a huge factor
• INACTIVITY!!!
• Trauma
• Surgery
• Burns
• Injury to vessels,
• Procoagulant substances from tissues
• Reduced t-PA activity

75. ARTERIAL/CARDIAC THROMBI
• ACUTE MYOCARDIAL INFARCTION =
OLD ATHEROSCLEROSIS + FRESH
THROMBOSIS
• ARTERIAL THROMBI also may send
fragments DOWNSTREAM, but these
fragments may contain flecks of
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

76. ATHEROEMBOLI
• “CHOLESTEROL” clefts are
components of atherosclerotic
plaques, NOT thrombi!!!

77. Disseminated Intravascular Coagulation
D.I.C.
• OBSTETRIC COMPLICATIONS
• ADVANCED MALIGNANCY
NOT a primary disease
CONSUMPTIVE coagulopathy, e.g.,
reduced platelets, fibrinogen, F-VIII and
other consumable clotting factors,
brain, heart, lungs, kidneys,
MICROSCOPIC ONLY

79. EMBOLISM
•Pulmonary
• Systemic (Mural Thrombi and
Aneurysms)
• Fat
• Air
• Amniotic Fluid

80. PULMONARY EMBOLISM
• 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

83. 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, kidneys, legs

84. OTHER EMBOLI
•FAT (long bone fx’s )
•AIR (SCUBA bends)
•AMNIOTIC FLUID,
very prolonged or difficult
delivery, high mortality

87. INFARCTION
• Defined as an area of necrosis*
secondary to decreased blood
flow
• HEMORRHAGIC vs. ANEMIC
• RED vs. WHITE
–END ARTERIES vs. NO END ARTERIES
• ACUTEORGANIZATIONFIBROSIS

88. INFARCTION FACTORS
• NATURE of VASCULAR SUPPLY
• RATE of DEVELOPMENT
–SLOW (BETTER)
–FAST (WORSE)
• VULNERABILITY to HYPOXIA
–MYOCYTE vs. FIBROBLAST
• CHF vs. NO CHF

91. HEART

92. SHOCK
• Pathogenesis
–Cardiac
–Septic
–Hypovolemic
• Morphology
• Clinical Course

93. SHOCK
• Definition: CARDIOVASCULAR COLLAPSE
• Common pathophysiologic features:
– INADEQUATE CARDIAC OUTPUT and/or
– INADEQUATE BLOOD VOLUME

94. GENERAL RESULTS
• INADEQUATE TISSUE PERFUSION
• CELLULAR HYPOXIA
• UN-corrected, a FATAL outcome

95. 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)

96. CARDIOGENIC shock
• MI
• VENTRICULAR RUPTURE
• ARRHYTHMIA
• CARDIAC TAMPONADE
• PULMONARY EMBOLISM (acute RIGHT
heart failure or “cor pulmonale”)

97. HYPOVOLEMIC shock
• HEMORRHAGE, Vasc. compartmentH2O
• VOMITING, Vasc. compartmentH2O
• DIARRHEA, Vasc. compartmentH2O
• BURNS, Vasc. compartmentH2O

98. SEPTIC shock
• 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” antigents by staph are the
prime example.)

99. SEPTIC shock events*
(overwhelming infection)
• Peripheral vasodilation
• Pooling
• Endothelial Activation
• DIC
* Think of this as a TOTAL BODY
inflammatory response

100. 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

101. ENDOTOXINS

102. SEPTIC shock events
(linear sequence)
• SYSTEMIC VASODILATION (hypotension)
• ↓ MYOCARDIAL CONTRACTILITY
• DIFFUSE ENDOTHELIAL ACTIVATION
• LEUKOCYTE ADHESION
• ALVEOLAR DAMAGE (ARDS)
• DIC
• VITAL ORGAN FAILURE CNS

103. CLINICAL STAGES of shock
•NON-PROGRESSIVE
•PROGRESSIVE
•IRREVERSIBLE

104. NON-PROGRESSIVE
• COMPENSATORY MECHANISMS
•CATECHOLAMINES
• VITAL ORGANS PERFUSED

105. PROGRESSIVE
• HYPOPERFUSION
• EARLY “VITAL” ORGAN FAILURE
• OLIGURIA
•ACIDOSIS

106. IRREVERSIBLE
•HEMODYNAMIC
CORRECTIONS
of no use

107. PATHOLOGY
• 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?)

108. ARDS/DAD

109. MYOCARDIAL NECROSIS

110. ATN

111. DIC

112. CLINICAL PROGRESSION
of SYMPTOMS
• Hypotension 
• Tachycardia 
• Tachypnea 
• Warm skin Cool skin Cyanosis
• Renal insufficiency
• Obtundance
• Death