First Foundations in Pathology, Part 4:

Hemodynamic Disorders
Paul G. Koles, MD
Asst. Prof. Pathology & Surgery
Director of Pathology Education
Boonshoft School of Medicine at Wright State University

Normal body composition

Water composes about 60% of total body mass
3 body compartments containing H2O:

= 70%

= 25%

= 5%

Pathophysiology of Edema
Anatomic structures
which drain excess
interstitial fluid into
venous blood:

Two opposing
major factors
governing fluid
movement between
vascular and
interstitial space.

Differential dx: causes of edema (1)

Differential dx: causes of edema (2)

History: 66 yo male smoker admitted for increasing shortness of

breath; chest x-ray shows left pleural effusion. History of
atherosclerotic heart disease, previous myocardial infarction, and
chronic congestive heart failure. Has had three previous pleural
effusions that were transudates with no significant inflammation. You
are on call for the medical service and assist the ER doc with
pleurocentesis. After successful removal 1100 cc yellow fluid, he
asks, What lab studies do you want on this fluid?
You say:
Cytologic Diagnosis?

Prognosis?

Clinical manifestations of edema

Clinical Signs
Bilateral symmetrical edema of skin &
subcutis of both legs below knees in
57-year-old man whose only complaint
is shortness of breath
Unilateral edema of one arm in a 60year-old female with a mastectomy
scar on that side
Periorbital edema with slight edema in
all four extremities, not much different
in lower legs vs. upper legs

Most Likely Cause(s)

Hemodynamic terminology

: locally increased blood caused

by arteriolar dilation with augmented inflow, as in
a working muscle or acute inflammation

: locally increased blood due to

impaired venous outflow (lungs in heart failure)
Is this hypertrophic liver
hyperemic or congested?

Hemorrhage
Definition: extravasation of blood because of
vessel rupture
Causes:
Mechanical trauma
Atherosclerosis of aorta

rupture with acute retroperitoneal hemorrhage

Increased hydrostatic pressure (obstruction or
hypertension)

causing weakened or necrotic wall

invading through vessel wall

Hemorrhagic diathesis (coagulation and platelet
disorders)

Nomenclature: hemorrhage

: hemorrhage accumulated within

a confined space

:1-3 mm hemorrhages skin, mucosa

:3-10 mm hemorrhage skin, mucosa

: >1cm hemorrhage skin/subcutis

: hemorrhage into joint

Hemostasis overview
Normal hemostasis
Maintain blood fluid within vessels
Induce rapid localized plug at injury site

Thrombosis
Formation of blood clot within vessel
(appropriately or inappropriately)

Three components which regulate normal

hemostasis / thrombosis:

Hemostasis
sequence 1

Hemostasis sequence 2

Dualistic endothelial cell function

Procoagulant (favors thrombosis)

Green molecule?

Anticoagulant (inhibits thrombosis)

Orange molecule?

Platelet response to injury

Platelets encounter extravascular matrix
molecules: collagen, proteoglycans,
fibronectin
Platelets respond in three phases:
1=
2=
3=

Platelet secretion (release reaction)

Secretion of granule contents after adhesion:

ADP: promotes aggregation with other platelets

Ionized calcium: enhances coagulation cascade
Thromboxane A2: further aggregation & vasoconstriction
Serotonin, histamine, epinephrine (promoting aggregation
& vasoconstriction )

Activated platelets express surface phospholipid

complex, providing binding sites for calcium and
factors involved in the intrinsic clotting pathway

Disorders of Platelet Function

Deficient Gp1b
receptor on platelets
for vWF:

Deficient Gp IIbIIIa complex:

Deficient von Willebrands factor:

Coagulation Cascade: 3rd component

Central role of thrombin

Functions:
1) Formation of
fibrin
2) Induces platelet
aggregation
3) Activates
endothelium
4) Activation of
lymphocytes &
monocytes

Fig. 4-11, Pathologic Basis of Disease, 2006.

Fibrinolytic system: restriction of

clotting to local site of injury

Application: Lab
evidence of excessive
fibrinolysis (DIC)?
(3 nonmorphologic
abnormalities)

1)
2)
3)

One RBC
morphologic
abnormality?
(not sensitive
or specific)
Fig. 4-12, Pathologic Basis of Disease, 2005

Thrombosis: a clot within vessel

Predisposing factors: Virchows triad
Trauma,
atherosclerosis,
vasculitis
Atherosclerosis,
aneurysms,
valvular heart
disease
Inherited
or
acquired

What is the most common inherited defect,

affecting 2-15% of Caucasians, leading to
increased hypercoagulability because of
resistance to effect of protein C?

Which group (genetic or

acquired) accounts for >90% of
clinically significant thromboses
in US population?

Venous thrombosis
Most common anatomic location?
Most serious complication?

Disseminated intravascular coagulation

(DIC)
Not a primary disease, but complication of
diseases with widespread activation of thrombin
Pathophysiology:
fibrin-platelet thrombi in microcirculation, with concurrent
consumption of platelets and coagulation proteins.
RBCs may be torn and fragmented by fibrin thrombi.
Diffuse activation of fibrinolysis, generating increased
FDPs & D-dimer (lab evidence DIC)

Treatment: diagnose and treat underlying disease;

buy time (not cure) with administration of platelets
and fresh frozen plasma

Peripheral smear in DIC: pathogenesis of

schistocyte formation?

Embolism
Definition: detached intravascular solid, liquid, or
gaseous mass carried by blood to a site distant from
its origin.
Types:

:> 99% of all emboli

Fat or marrow: post-trauma to bones
Cholesterol: after invasive vascular procedures, presenting
as hematuria or renal insufficiency due to multiple renal
microinfarctions
Tumor: from neoplasms invading vessels
Foreign body: intravenous devices/ drug abuse

: 1/50,000 deliveries; mortality >80% with

complications of pulmonary edema/DIC

Pulmonary thromboembolism

Occlusion large pulmonary artery

Occlusion of
small artery
results in
what type of
infarction?

Pulmonary thromboembolism

200,000 deaths/year in US
Many are clinically silent if small
: thrombus occluding main pulmonary artery
at bifurcation

: thromboembolus originating in veins,

passing through atrial or ventricular septal defect, into arterial side
Sudden death: likely if >60% pulmonary circulation is obstructed
with emboli (acute right heart failure)

results from occlusion of medium-sized vessels

(dual bronchial blood supply prevents infarction)

arterioles

results from occlusion of small end arteries or

Infarction
Definition: Ischemic necrosis of tissue
caused by occlusion of arterial supply
(usually) or venous outflow (less common)
Huge problem: > 50% US mortality due
to atherosclerotic vascular disease causing
myocardial & cerebral infarctions
Usual histopathology:
Histopathology in brain:
Resolution: fibrous scar with loss function

Infarction, gross features

Lung, acute hemorrhagic

infarction (note wedge-shape)

Kidney, remote healed

infarction (fibrous scar)

Shock
Def.: systemic hypoperfusion due to reduced cardiac
output or reduced effective blood volume.
Major causes:

: myocardial pump failure

:loss blood/plasma volume

: systemic microbial infection

: spinal cord injury

: generalized IgE-mediated
hypersensitivity response, with widespread vasodilation,
increased capacitance, & increased vascular permeability

Shock: 3 most common types

Septic shock
25-50% mortality rate, >100,000 deaths/yr.
Increasing incidence (intensive care,
invasive procedures, longer lifespan, more
immunocompromised patients)
70% cases produced by which type of
bacteria ?

:
lipopolysaccharides (LPS) released when
bacterial cell walls are degraded by
inflammation or antibiotic therapy.

Cytokine cascade in
Gram-negative sepsis
Produced by:
Produced by:
Produced by:

Fig. 4-21, Pathologic Basis of Disease, 2005

Clinical sequelae of sepsis

NO =
PAF =

Fig. 4-22, Pathologic Basis of Disease, 2005

Stages of shock
Nonprogressive phase
Reflex mechanisms activated and perfusion of
vital organs maintained

Progressive stage
Persistent tissue hypoperfusion leads to
widespread hypoxic cell damage, metabolic
acidosis, prolonged vasodilation

Irreversible stage
Severe cellular injury with multiorgan failure,
dominated by renal, lungs, heart