ch4-hemodyn
DESCRIPTION
pathologyTRANSCRIPT
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)
• Hemostasis (keeping blood as a fluid)
• 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, -PERICARDIUM
• 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 ONCOTICPRESSURE (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 hypoperfusionIncreased renin-angiotensin-aldosterone secretion
INFLAMMATION• Acute inflammation
• Chronic inflammation
• Angiogenesis
Jv = ([Pc − Pi] − σ[πc − πi])
CHF EDEMA• INCREASED VENOUS PRESSURE
DUE TO FAILURE
• DECREASED RENAL PERFUSION, triggering of RENIN-ANGIOTENSION-ALDOSTERONE complex, resulting ultimately in SODIUM RETENTION
HEPATIC ASCITES
• PORTAL HYPERTENSION
• HYPOALBUMINEMIA
ASCITES
RENAL EDEMA• SODIUM RETENTION
• PROTEIN LOSING GLOMERULOPATHIES (NEPHROTIC SYNDROME)
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
“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)
HYPEREMIAActive Process
CONGESTIONPassive ProcessAcute or Chronic
CONGESTION• LUNG
–ACUTE
–CHRONIC
• LIVER–ACUTE
–CHRONIC
• CEREBRAL
ACUTE PASSIVE HYPEREMIA/CONGESTION,
LUNG
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
HEMATOMAvs.
“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 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, 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
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, α and δ• 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)
THROMBOSIS• Virchow’s TRIANGLE
ENDOTHELIAL INJURY
ABNORMAL FLOW(NON-LAMINAR)
HYPER-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 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 methyltetrahydrofolate 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.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
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
• SHOCKNOT 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
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
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
• ACUTEORGANIZATIONFIBROSIS
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. 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” 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 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
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 PROGRESSIONof SYMPTOMS
• Hypotension • Tachycardia • Tachypnea • Warm skin Cool skin Cyanosis
• Renal insufficiency• Obtundance
• Death