HEMODYNAMIC DISORDERS,

THROMBOSIS AND SHOCK

Overview

Hemodynamic
Disorders
Edema

(increased
fluid in the ECF)
Hyperemia
(INCREASED flow)
Congestion
(INCREASED backup)

Hemostatic Disorders
Hemorrhage

(extravasation)
Thrombosis (clotting
blood)
Embolism (downstream
travel of a clot)

Overview

Infarction (death of tissues w/o blood)

Shock (circulatory failure/collapse)

HEMODYNAMIC
DISORDERS

Hemodynamics
(Starling-Landis Law)

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

Body Water

Makes up 60% of body

Locations of water in body:

2/3

intracellular
1/3 interstitial
5% intravascular

EDEMA is shift of water from intravascular to

interstitial space.

Edema

Usually caused by/involves heart, liver and kidneys

Caused by:
Increased

hydrostatic pressure
Reduced oncotic pressure
Lymphatic obstruction
Sodium/water retention

Edema

Hydro Thorax
Pericarium
Peritonium

Effusions
Ascites
Anasarca

Subcutaneous (Pitting) Edema

Periorbital Edema

Increased Hydrostatic Pressure

Impaired venous return

Congestive heart failure
Constrictive pericarditis
Ascites (liver cirrhosis)
Venous obstruction or compression

Increased Hydrostatic Pressure

Thrombosis
External pressure (e.g., mass)
Lower extremity inactivity with prolonged
dependency
Arteriolar dilation
Heat
Neurohumoral dysregulation

Reduced Oncotic Pressure

Protein-losing glomerulopathies (nephrotic

syndrome)
Liver cirrhosis (ascites)
Malnutrition
Protein-losing gastroenteropathy

Lymphatic Obstruction

Lymphatic system responsible for draining ECF

Lymphatic disorders (lymphedema):

Inflammatory
Neoplastic

Post-surgical
Post-irradiation

Na+ Retention

Excessive salt intake with renal insufficiency

Increased tubular reabsorption of sodium

Renal hypoperfusion Increased renin-angiotensinaldosterone secretion

Inflammation

Areas of increased vascular permeability (i.e.,

inflammation) or areas of increased blood vessels
(i.e., angiogenesis) will appear edematous.

CHF Edema

Increased venous pressure due to failure

Decreased renal perfusion Activation of reninangiotensin-aldosterone system Sodium retention

Hepatic Ascites

Portal hypertension
causes edema of
organs and tissues with
portal circulation
Hypoalbuminemia

Renal Edema

Sodium retention

Protein-losing glomerulopathies (e.g., nephrotic

syndrome)

Transudate vs Exudate

Transudate
results

from disturbance of Starling forces

specific gravity < 1.012
protein content < 3 g/dl; low LDH

Exudate
results

from damage to the capillary wall

specific gravity > 1.012
protein content > 3 g/dl; high LDH

Hyperemia & Congestion

Hyperemia
Active

process

Congestion
Passive

process
Acute or chronic
Lung, liver or cerebral

Lung Edema

CHF

Acute Passive Liver Congestion

Chronic Passive Liver Congestion

Cerebral Edema

HEMOSTATIC DISORDERS

Hemorrhage

Extravasation beyond
vessel
Hemorrhagic diathesis
bleeding tendency

Hemorrhage

Hematoma
Petechiae:

1 to 2mm
Purpura: <1cm
Ecchymoses: >1cm

Hemorrhage

Hemo Thorax
Pericardium
Peritoneum

Hemarthrosis

Evolution of Hemmorhage

Acute Chronic

Purple Green Brown

Hgb Bilirubin Hemosiderin

END OF PART 1

Hemostasis

Results from a regulated processes that:

Maintains

blood in a fluid state in normal vessels

Forms a hemostatic clot (plug) at the site of a vascular
injury

Components:
Vascular

wall

Platelets
Coagulation

cascade

Thromobosis

Pathologic counterpart of hemostasis

Blood clot (thrombus) formation within intact vessels

Influenced by the same components as hemostasis

Events Following Vascular Injury

ARTERIOLAR VASOCONSTRICTION
Reflex

neurogenic mechanism
Endothelin from endothelial cells

THROMBOGENIC SUBENDOTHELIAL ECM

EXPOSURE at injury site causes platelet:
Adhesion
Activation

(degranulation)
Aggregation (1 HEMOSTASIS)

Events Following Vascular Injury

TISSUE FACTOR released by endothelium and

platelets activates coagulation cascade thrombin
fibrin (2 HEMOSTASIS)
FIBRIN polymerizes, TPA limits plug.

HEMOSTASIS

Hemostasis Components

VASCULAR WALL ENDOTHELIUM

PLATELETS

COAGULATION CASCADE

ENDOTHELIUM

In normal vessels:
ANTIPLATELET

PROPERTIES
ANTICOAGULANT PROPERTIES
FIBRINOLYTIC PROPERTIES

During vessel injury

PRO-COAGULANT

PROPERTIES

ENDOTHELIUM (Normal)

Anti-platelet
properties
Protection

from the
subendothelial ECM
Degrades ADP (inhibits
aggregation)

ENDOTHELIUM (Normal)

Anti-coagulant
properties
Membrane

HEPARINlike molecules
Makes
THROMBOMODULIN
Protein-C
TISSUE FACTOR
PATHWAY INHIBITOR

ENDOTHELIUM (Normal)

Fibrinolytic properties
(TPA)

ENDOTHELIUM (Vessel Injury)

PROTHROMBOTIC
PROPERTIES
vWF,

which binds
Platelets
TISSUE FACTOR (with
platelets)
Plasminogen inhibitors

PLATELETS

ALPHA GRANULES
Fibrinogen
Fibronectins

(precursors to integrins)
Factors V and VIII
Platelet factor 4 and TGF-beta

DELTA GRANULES (DENSE BODIES)

ADP/ATP,

Ca+, histamine, serotonin and epinephrine

With endothelium, form TISSUE FACTOR

Platelet Alpha Degranulation

PLATELET PHASES

ADHESION
ACTIVATION (i.e., release or secretion 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

Binding of agonists to platelet surface receptors

Intracellular protein PHOSPHORYLATION
Degranulation
BOTH and granules

PLATELET AGGREGATION STIMULI

ADP

TxA2 (Thromboxane A2)

THROMBIN from coagulation cascade

FIBRIN further strengthens and hardens and

contracts the platelet plug

PLATELET EVENTS

ADHERENCE to ECM
SECRETION of ADP and TxA2
EXPOSURE of phospholipid complexes
Express TISSUE FACTOR
PRIMARYSECONDARY PLUG
STRENGTHENED by FIBRIN

COAGULATION CASCADE

INTRINSIC (Contact)/EXTRINSIC (Tissue) FACTORS:

Enzymes
Prothrombin (II) Thrombin (IIa)
Fibrinogen (I) Fibrin (Ia)
Proenzymes

Cofactors
Ca++
Phospholipid

(from platelet membranes)

Vit-K dep. factors: II, VII, IX, X, Proteins S, C, Z

COAGULATION CASCADE

THROMBOSIS

Virchows Triangle

ENDOTHELIAL INJURY

Includes any disturbance in the dynamic balance of

the pro- and antithrombotic effects of endothelium,
not only physical damage

ABNORMAL FLOW

May bring platelets into contact with endothelium

and/or ECF
NON-LAMINAR FLOW
TURBULENCE

STASIS

1 HYPERCOAGULABILITY
(INHERITED)

Most common: Factor V (Leiden) and Prothrombin

(20210A) defects
Common:
5,10-Methylenetetrahydrofolate

reductase

(homozygous C677T mutation)

Increased levels of factors VIII, IX, XI, or fibrinogen

1 HYPERCOAGULABILITY
(INHERITED)

Rare:
Antithrombin

III deficiency
Protein C deficiency
Protein S deficiency

Very rare: Fibrinolysis defects

2 HYPERCOAGULABILITY
(ACQUIRED)

Prolonged bedrest or
immobilization
Myocardial infarction
Atrial fibrillation
Tissue injury (surgery,
fracture, burn)
Cancer
Prosthetic cardiac
valves

Disseminated
intravascular
coagulation
Heparin-induced
thrombocytopenia
Antiphospholipid
antibody syndrome

2 HYPERCOAGULABILITY
(ACQUIRED)

Cardiomyopathy
Nephrotic syndrome
Hyperestrogenic states (pregnancy and postpartum)
Oral contraceptive use
Sickle cell anemia
Smoking

THROMBI MORPHOLOGY

ADHERENCE TO VESSEL WALL

HEART

(MURAL)
ARTERY (OCCLUSIVE/INFARCT)
VEIN

OBSTRUCTIVE vs. NON-OBSTRUCTIVE

RED or YELLOW

FATE OF THROMBI

Propagation accumulation of additional platelets

and fibrin
Embolization dislodge and travel to other sites in
the vasculature

FATE OF THROMBI

Dissolution rapid shrinkage and total

disappearance of recent thrombi
Organization and recanalization
Older

thrombi become organized by the ingrowth of

endothelial cells, smooth muscle cells and fibroblasts.
Capillary channels form and re-establish the continuity
of the original lumen.

EMBOLISM

Pulmonary

Systemic (mural thrombi and aneurysms)

Fat

Air

Amniotic Fluid

INFARCTION

INFARCTION

Defined as an area of necrosis secondary to

decreased blood flow
Causes/Types:
HEMORRHAGIC

vs. ANEMIC
RED (Dual Circulations) vs. WHITE (End-arterial
Circulations)

Stages:
ACUTE

ORGANIZATION FIBROSIS

INFARCTION FACTORS

Nature of the vascular supply

Single

end arteries such as kidney and spleen

Dual blood supply such as lung and liver

Rate of occlusion development

SLOW

(BETTER)
FAST (WORSE)

INFARCTION FACTORS

Vulnerability to hypoxia
Neurons:

3 to 4 minutes
Myocardial cells: 20 to 30 minutes
Myocardial fibroblasts: many hours

Oxygen content of blood

Normal

individual vs. anemic or cyanotic patient

END OF PART 2