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)
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 RENIN-ANGIOTENSIONALDOSTERONE 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
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)

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

75_40xr.fpx

CHRONIC PASSIVE
HYPEREMIA/CONGESTION,
LUNG

Acute Passive Congestion,

Liver
au135b_b_40xr.fpx

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, IL-1, TNF
ACTIVATED by ANYTHING which
disrupts it

PLATELETS
ALPHA GRANULES
Fibrinogen
Fibronectins (precursors to integrins)
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 made in
endothelial cells, 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)

THROMBOSIS
Virchows TRIANGLE
ENDOTHELIAL
INJURY

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

HYPERCOAGULABILITY

(INHERITED)
COMMONEST: Factor V (Leiden) and
Prothrombin (20210A) defects
Common: Mutation in prothrombin gene,
Mutation in methylenetetrahydrofolate gene
(MTHFR), homocysteinemethionine

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!!!
Trauma

Surgery

Burns
Injury to vessels
Procoagulant substances from tissues
Reduced t-PA activity, therefore reduced plasmin

ARTERIAL/CARDIAC THROMBI

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

ATHEROEMBOLI

CHOLESTEROL clefts are

components of atherosclerotic
arterial plaques, NOT venous
thrombi!!!

Disseminated Intravascular Coagulation

D.I.C.
OBSTETRIC COMPLICATIONS
ADVANCED MALIGNANCY, M3, APML

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

EMBOLISM

Pulmonary

Systemic (Mural Thrombi and

Aneurysms)

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, chokes,

staggers)

AMNIOTIC FLUID, very

prolonged or difficult delivery,
high mortality

Amniotic Fluid Embolism

INFARCTION

Defined as an area of necrosis*

secondary to decreased blood
flow (really oxygen)
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, global
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