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
• HYDRO-
– -THORAX, -PERICARDIUM, -PERITONEAL
• EFFUSIONS, ASCITES, ANASARCA
 INCREASED HYDROSTATIC
PRESSURE (i.e.,VENOUS)
• 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-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, 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 phospholipid
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 HYPER-

(NON-LAMINAR) COAGULATION
 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)
• 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
 ˚
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
 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. (CALF,
D.V.T.
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”)
•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”?
 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.)
 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