HEMODYNAMIC DISORDERS

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HEMODYNAMIC DISORDERS
Jv (Pc - Pi - spc - pi)
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• Hemodynamic Disorders
• Thromboembolic Disease
• Shock

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Overview

• Edema
• Hyperemia
• Congestion
• Hemorrhage
• Hemostasis
• Thrombosis
• Embolism
• Infarction
• Shock

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EDEMA

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

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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

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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

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REDUCED PLASMA ONCOTICPRESSURE (HYPOPROTEINEMIA)

• Protein-losing glomerulopathies (nephrotic
  syndrome)
• Liver cirrhosis (ascites)
• Malnutrition
• Protein-losing gastroenteropathy

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LYMPHATIC OBSTRUCTION(LYMPHEDEMA)

• Inflammatory
• Neoplastic
• Postsurgical
• Postirradiation

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Na RETENTION

• Excessive salt intake with renal insufficiency
• Increased tubular reabsorption of sodium
• Renal hypoperfusion?Increased renin-angiotensin-al
  dosterone secretion

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INFLAMMATION

• Acute inflammation
• Chronic inflammation
• Angiogenesis

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Jv (Pc - Pi - spc - pi)
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CHF EDEMA

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

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HEPATIC ASCITES

• PORTAL HYPERTENSION
• HYPOALBUMINEMIA

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ASCITES
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RENAL EDEMA

• SODIUM RETENTION
• PROTEIN LOSING GLOMERULOPATHIES (NEPHROTIC
  SYNDROME)

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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

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Pitting Edema
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Transudate vs Exudate

• Transudate
• results from disturbance of Starling forces
• specific gravity lt 1.012
• protein content lt 3 g/dl
• Exudate
• results from damage to the capillary wall
• specific gravity gt 1.012
• protein content gt 3 g/dl

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HYPEREMIA/(CONGESTION)
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HYPEREMIA

• Active Process

CONGESTION Passive Process Acute or Chronic
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CONGESTION

• LUNG
• ACUTE
• CHRONIC
• LIVER
• ACUTE
• CHRONIC
• CEREBRAL

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ACUTE PASSIVE HYPEREMIA/CONGESTION, LUNG
?
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Kerley B Air Bronch-ogram
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CHRONIC PASSIVE HYPEREMIA/CONGESTION, LUNG
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Acute Passive Congestion, Liver
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Acute Passive Congestion, Liver
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CHRONIC PASSIVE HYPEREMIA/CONGESTION, LIVER
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HEMORRHAGE

• EXTRAVASATION beyond vessel
• HEMORRHAGIC DIATHESIS
• HEMATOMA (implies MASS effect)
• DISSECTION
• PETECHIAE (1-2mm) (PLATELETS)
• PURPURA lt1cm
• ECCHYMOSES gt1cm (BRUISE)
• HEMO- -thorax, -pericardium, -peritoneum,
  HEMARTHROSIS
• ACUTE, CHRONIC

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EVOLUTION of HEMORRHAGE

• ACUTE? CHRONIC
• PURPLE? GREEN? BROWN
• HGB? BILIRUBIN? HEMOSIDERIN

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HEMATOMAvs.CLOT
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HEMOSTASIS

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

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SEQUENCE of EVENTSfollowing 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

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PLAYERS

• ENDOTHELIUM
• PLATELETS
• COAGULATION CASCADE

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ENDOTHELIUM

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

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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)

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ENDOTHELIUM

• PROTHROMBOTIC PROPERTIES
• Makes vWF, which binds Plats?Coll
• Makes TISSUE FACTOR (with plats)
• Makes Plasminogen inhibitors

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ENDOTHELIUM

• ACTIVATED by INFECTIOUS AGENTS
• ACTIVATED by HEMODYNAMICS
• ACTIVATED by PLASMA

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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

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NORMAL platelet on LEFT, DEGRANULATING ALPHA
GRANULE ON RIGHT AT OPEN WHITE ARROW
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PLATELET PHASES

• ADHESION
• SECRETION (i.e., release or activation or
  degranulation)
• AGGREGATION

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PLATELET ADHESION

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

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PLATELET SECRETION

• BOTH granules, a and d
• Binding of agonists to platelet surface receptors
  AND intracellular protein PHOSPHORYLATION

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PLATELET AGGREGATION

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

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PLATELET EVENTS

• ADHERENCE to ECM
• SECRETION of ADP and TxA2
• EXPOSE phospholipid complexes
• Express TISSUE FACTOR
• PRIMARY?SECONDARY PLUG
• STRENGTHENED by FIBRIN

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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

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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

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THROMBOSIS

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

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THROMBOSIS

• Virchows TRIANGLE

ENDOTHELIAL INJURY
ABNORMAL FLOW (NON-LAMINAR)
HYPER- COAGULATION
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ENDOTHELIAL INJURY

• Jekyll/Hyde disruption
• any perturbation in the dynamic balance of the
  pro- and antithrombotic effects of endothelium,
  not only physical damage

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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)

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ENDOTHELIUM

• PROTHROMBOTIC PROPERTIES
• Makes vWF, which binds Plats?Coll
• Makes TISSUE FACTOR (with plats)
• Makes Plasminogen inhibitors

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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
  methyltetrahydrofolate gene
• Rare Antithrombin III deficiency, Protein C
  deficiency, Protein S deficiency
• Very rare Fibrinolysis defects

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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

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MORPHOLOGY

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

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MURAL THROMBI, HEART
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FATE of THROMBI

• PROPAGATION (Downstream)
• EMBOLIZATION
• DISSOLUTION
• ORGANIZATION
• RECANALIZATION

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OCCLUSIVE ARTERIAL THROMBUS
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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

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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

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ATHEROEMBOLI

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

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Disseminated Intravascular CoagulationD.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

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EMBOLISM

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

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PULMONARY EMBOLISM

• USUALLY SILENT
• CHEST PAIN, LOW PO2, S.O.B.
• Sudden OCCLUSION of gt60 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

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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

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OTHER EMBOLI

• FAT (long bone fxs )
• AIR (SCUBA bends)
• AMNIOTIC FLUID, very prolonged or difficult
  delivery, high mortality

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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

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INFARCTION FACTORS

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

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HEART
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SHOCK

• Pathogenesis
• Cardiac
• Septic
• Hypovolemic
• Morphology
• Clinical Course

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SHOCK

• Definition CARDIOVASCULAR COLLAPSE
• Common pathophysiologic features
• INADEQUATE CARDIAC OUTPUT and/or
• INADEQUATE BLOOD VOLUME

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GENERAL RESULTS

• INADEQUATE TISSUE PERFUSION
• CELLULAR HYPOXIA
• UN-corrected, a FATAL outcome

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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)

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CARDIOGENIC shock

• MI
• VENTRICULAR RUPTURE
• ARRHYTHMIA
• CARDIAC TAMPONADE
• PULMONARY EMBOLISM (acute RIGHT heart failure or
  cor pulmonale)

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HYPOVOLEMIC shock

• HEMORRHAGE, Vasc. compartment?H2O
• VOMITING, Vasc. compartment?H2O
• DIARRHEA, Vasc. compartment?H2O
• BURNS, Vasc. compartment?H2O

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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.)

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SEPTIC shock events(overwhelming infection)

• Peripheral vasodilation?
• Pooling?
• Endothelial Activation?
• DIC
• Think of this as a TOTAL BODY inflammatory
  response

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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

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ENDOTOXINS
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SEPTIC shock events(linear sequence)

• SYSTEMIC VASODILATION (hypotension)?
• ? MYOCARDIAL CONTRACTILITY?
• DIFFUSE ENDOTHELIAL ACTIVATION?
• LEUKOCYTE ADHESION?
• ALVEOLAR DAMAGE? (ARDS)
• DIC
• VITAL ORGAN FAILURE? CNS

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CLINICAL STAGES of shock

• NON-PROGRESSIVE
• PROGRESSIVE
• IRREVERSIBLE

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NON-PROGRESSIVE

• COMPENSATORY MECHANISMS
• CATECHOLAMINES
• VITAL ORGANS PERFUSED

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PROGRESSIVE

• HYPOPERFUSION
• EARLY VITAL ORGAN FAILURE
• OLIGURIA
• ACIDOSIS

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IRREVERSIBLE

• HEMODYNAMIC CORRECTIONS of no use

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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?)

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ARDS/DAD
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MYOCARDIAL NECROSIS
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ATN
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DIC
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CLINICAL PROGRESSIONof SYMPTOMS

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