HEMODYNAMIC

DISORDERS

Jv = ([Pc Pi] [c i])

 Hemodynamic Disorders Thromboembolic Disease Shock

Overview
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

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] [c i])

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)

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

EDEMA

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

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 cascadethrombinfibrin (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 PlatsColl 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

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, and
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 PRIMARYSECONDARY PLUG STRENGTHENED by FIBRIN

COAGULATION CASCADE
INTRINSIC(contact)/EXTRINSIC(TissFac) ProenzymesEnzymes 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
(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)

 Virchows TRIANGLE
ENDOTHELIAL INJURY

THROMBOSIS

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 PlatsColl 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) Cardiomyopathy Nephrotic syndrome Hyperestrogenic states (pregnancy) Oral contraceptive use Sickle cell anemia Smoking, Obesity

Lower risk for thrombosis:

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, THIGH, PELVIC) V.T. CHF a huge factor

D.V.T.

INACTIVITY!!!
Trauma

Surgery
Burns Injury to vessels, Procoagulant substances from tissues Reduced t-PA activity

 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

ARTERIAL/CARDIAC THROMBI

 CHOLESTEROL clefts are components of atherosclerotic arterial plaques, NOT venous thrombi!!!

ATHEROEMBOLI

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

Pulmonary
Aneurysms)

EMBOLISM

Systemic (Mural Thrombi and 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 fxs, 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

ACUTEORGANIZATIONFIBROSIS

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

HYPOVOLEMIC shock
HEMORRHAGE, Vasc. compartmentH2O VOMITING, Vasc. compartmentH2O DIARRHEA, Vasc. compartmentH2O BURNS, Vasc. compartmentH2O

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 superantigens by staph are the prime example.)

SEPTIC shock events*

(overwhelming infection)
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
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
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