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

•Hemodynamic
Disorders
•Thromboembolic
Disease
•Shock

Overview
• Edema (increased fluid in the ECF)
• Hyperemia (INCREASED flow)
• Congestion (INCREASED backup)
• Hemorrhage (extravasation)
• Hemo-stasis* (opposite of thrombosis)
• Thrombosis (clotting blood)
• Embolism (downstream travel of a clot)
• Infarction (death of tissues w/o blood)
• Shock (circulatory failure/collapse)

EDEMA= ↑ECF
•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 FROM EITHER DIRECTION
• CELLECF VASC
• HYDRO-
– -THORAX, -PERICARDIUM, -PERITONEAL
• EFFUSIONS, ASCITES, ANASARCA

INCREASED HYDROSTATIC
PRESSURE (i.e.,VENOUS)
• Impaired venous return
• Congestive heart failure
• Constrictive pericarditis
• Ascites (liver cirrhosis) Liver is only a Portal-Caval filter?
• 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-angiotensin-
aldosterone secretion

INFLAMMATION
• Acute inflammation (r,c,d,T)
• Chronic inflammation
• Angiogenesis

Jv = ([Pc − Pi] − σ[πc − πi])

CHF EDEMA-2 REASONS
• INCREASED VENOUS PRESSURE
DUE TO FAILURE
• DECREASED RENAL PERFUSION,
triggering of RENIN-
ANGIOTENSION-ALDOSTERONE
complex, resulting ultimately in
SODIUM RETENTION

HEPATIC ASCITES- 2 REASONS
• PORTAL HYPERTENSION
• HYPOALBUMINEMIA

ASCITES

RENAL EDEMA- 2
REASONS
• SODIUM RETENTION
• PROTEIN LOSING
GLOMERULOPATHIES
(NEPHROTIC SYNDROME)

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 (water)
– results from disturbance of Starling forces
– specific gravity < 1.012
– protein content < 3 g/dl, LDH LOW, ↓ Cells
• Exudate (goo)
– results from damage to the capillary wall
– specific gravity > 1.012
– protein content > 3 g/dl, LDH HIGH, ↑ Cells

HYPEREMIA/(CONGESTION)

HYPEREMIA
Active Process
CONGESTION
Passive Process
Acute or Chronic

CONGESTION
• LUNG, best example R. CHF
–ACUTE
–CHRONIC, hemosiderin
• LIVER, best example L. CHF
–ACUTE
–CHRONIC, necrosis
• CEREBRAL

ACUTE PASSIVE
HYPEREMIA/CONGESTION,
LUNG

septae
alveoli

Kerley B
Air
Bronch-
ogram

CHRONIC PASSIVE
HYPEREMIA/CONGESTION,
LUNG

Acute Passive Congestion,
Liver

Acute Passive Congestion,
Liver

CHRONIC PASSIVE
HYPEREMIA/CONGESTION, LIVER

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

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

HEMATOMA
vs.
“CLOT”
(Pre-mortem vs. Post-mortem)

HEMO”STASIS”
• OPPOSITE of THROMBOSIS
–PRESERVE LIQUIDITY OF BLOOD
–“PLUG” sites of vascular injury
• THREE COMPONENTS
–1 VASCULAR WALL, i.e., endoth/ECM
–2 PLATELETS, “PRIMARY” COAG.
–3 COAGULATION CASCADE, or
“SECONDARY” COAGULATION

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
•1) ENDOTHELIUM
•2) PLATELETS
•3) COAGULATION
“CASCADE”, or SEQ.

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

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

ENDOTHELIUM
• ACTIVATED by INFECTIOUS AGENTS
• ACTIVATED by HEMODYNAMICS
• ACTIVATED by PLASMA
• ACTIVATED by ANYTHING which
disrupts it, including physical trauma
“DISRUPTION”

PLATELETS
• ALPHA GRANULES
– Fibrinogen
– Fibronectin, a big CAM
– Factor-V, Factor-VIII
– Platelet factor 4 (anti-anti-), 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) (prothrombotic)
• 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 phospholip. Complexes
• Express TISSUE FACTOR
• PRIMARYSECONDARY PLUG
• STRENGTHENED by FIBRIN

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

TF
III

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

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

THROMBOSIS
• Virchow’s TRIANGLE
ENDOTHELIAL
INJURY
ABNORMAL FLOW
(NON-LAMINAR)
HYPER-
COAGULATION, 1° 2 °

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

1˚ HYPERCOAGULABILITY
(INHERITED, GENETIC)
• COMMONEST: Factor V
(Leiden) 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

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 “anti-”coagulant syndrome)
• Lower risk for thrombosis:
– 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!!! (of lower extremities)
• Trauma
• Surgery
• Burns
• Injury to vessels,
• Procoagulant substances from tissues
• Reduced t-PA activity (Homeostasis shift)

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

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

Disseminated Intravascular Coagulation
D.I.C.
• OBSTETRIC COMPLICATIONS
• ADVANCED MALIGNANCY
• SHOCK (almost “synonymous” with DIC)
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
• 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: NON
ADHERENT!!!

SYSTEMIC EMBOLI
• “PARADOXICAL” EMBOLI due to R>L
SHUNT
• 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

OTHER EMBOLI
•FAT (long bone fx’s )
•AIR (SCUBA “bends”,
sex?)
•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. NO END ARTERIES
• ACUTEORGANIZATIONFIBROSIS

INFARCTION FACTORS
• NATURE of VASCULAR SUPPLY
• 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
• 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
• MI
• VENTRICULAR RUPTURE
• ARRHYTHMIA
• CARDIAC TAMPONADE
• PULMONARY EMBOLISM (acute RIGHT
heart failure or “cor pulmonale”)

HYPOVOLEMIC shock
• HEMORRHAGE, Vasc. compartmentH2O
• VOMITING, Vasc. compartmentH2O
• DIARRHEA, Vasc. compartmentH2O
• BURNS, Vasc. compartmentH2O
• HEAT “STROKE”? (really loss of blood
water due to severe dehydration)

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 (storm?) similar to those occurring
downstream in septic shock, “toxic shock” antigents by
staph are the prime example.)

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

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
• DIFFUSE ENDOTHELIAL ACTIVATION
• LEUKOCYTE ADHESION
• ALVEOLAR DAMAGE (ARDS)
• DIC
• VITAL ORGAN FAILURE CNS last

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
• 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
• Hypotension 
• Tachycardia 
• Tachypnea 
• Warm skin Cool skin Cyanosis
• Renal insufficiency
• Obtundance
• Death