Edema and Effusion 1

Question 1

Edema

Answer 1

Disorders that perturb cardiovascular, renal, or hepatic
function are often marked by the accumulation of fluid in
tissues

Question 2

(effusions

Answer 2

body cavities

Question 3

Noninflammatory edema

and effusions are common in many diseases

Answer 3

heart
failure, liver failure, renal disease, and severe nutritional
disorders

Question 4

Increased Hydrostatic Pressure

Answer 4

Increases in hydrostatic pressure are mainly caused by

disorders that impair venous return.

Question 5

If the impairment is

localized

Answer 5

DVT

Question 6

Conditions leading to systemic increases in venous

pressure

Answer 6

CHF

Question 7

Increased Hydrostatic Pressure

Answer 7

Under normal circumstances albumin accounts for almost
half of the total plasma protein; it follows that conditions
leading to inadequate synthesis or increased loss of
albumin from the circulation are common causes of
reduced plasma oncotic pressure.

Question 8

Hypoalbunemia

Answer 8

end-stage cirrhosis,

protein malnutrition

Question 9

An important

cause of albumin loss is

Answer 9

nephrotic syndromein
which albumin leaks into the urine through abnormally
permeable glomerular capillaries.

Question 10

reduced
plasma osmotic pressure leads in a stepwise fashion to edema,
reduced intravascular volume

Answer 10

renal hypoperfusion, and
secondary hyperaldosteronism. Not only does the ensuing salt
and water retention by the kidney fail to correct the plasma
volume deficit, but it also exacerbates the edema, because the
primary defect—a low plasma protein level—persists.

Question 11

Sodium and Water Retention

Answer 11

Increased salt retention—with obligate retention of
associated water—causes both increased hydrostatic
pressure (due to intravascular fluid volume expansion)
and diminished vascular colloid osmotic pressure (due to
dilution)

Question 12

Salt retention occurs

Answer 12

whenever renal function is
compromised, such as in primary kidney disorders and in
cardiovascular disorders that decrease renal perfusion. One of
the most important causes of renal hypoperfusion is congestive
heart failure, which (like hypoproteinemia) results in the
activation of the renin-angiotensin-aldosterone axis.

Question 13

In early

heart failure, this response is beneficial,

Answer 13

as the retention of
sodium and water and other adaptations, including increased
vascular tone and elevated levels of antidiuretic hormone,
improve cardiac output and restore normal renal perfusion.

Question 14

Lymphatic Obstruction

Answer 14

Trauma, fibrosis, invasive tumors, and infectious agents
can all disrupt lymphatic vessels and impair the clearance
of interstitial fluid, resulting in lymphedema in the
affected part of the body

Question 15

LO example

Answer 15

Filariasis

Question 16

Morphology Edema is easily

recognized grossly; microscopically,

Answer 16

it is
appreciated as clearing and
separation of the extracellular
matrix and subtle cell
swelling. Any organ or tissue
can be involved, but edema is
most commonly seen in
subcutaneous tissues, the
lungs, and the brain.

Question 17

Subcutaneous edema

Answer 17

can be
diffuse or more conspicuous in
regions with high hydrostatic
pressures. Its distribution is
often influenced by gravity
(e.g., it appears in the legs
when standing and the sacrum
when recumbent), a feature
termed dependent edema.

Question 18

Finger pressure over markedly
edematous subcutaneous
tissue displaces the interstitial
fluid and leaves a depression,

Answer 18

pitting edema

Question 19

Edema resulting from renal dysfunction often

appears initially in

Answer 19

body containing loose

connective tissue, such as the eyelids, Periorbital Edema

Question 20

pulmonary edema,

Answer 20

lungs are often
two to three times their normal weight, and sectioning
yields frothy, blood-tinged fluid—a mixture of air,
edema, and extravasated red cells.

Question 21

Brain edema

Answer 21

Localized or generalized depending on the nature and extent of the pathologic process or injury. The swollen brain exhibits narrowed sulci and distended gyri, which are compressed by the unyielding skull

Question 22

Effusions involving the pleural cavity

Answer 22

(hydrothorax

Question 23

pericardial cavity

Answer 23

hydropericardium

Question 24

peritoneal cavity

Answer 24

hydroperitoneum or ascites

Question 25

Transudative effusions are

typically

Answer 25

protein-poor, translucent and straw colored;
an exception are peritoneal effusions caused by
lymphatic blockage (chylous effusion), which may be
milky due to the presence of lipids absorbed from the
gut.

Question 26

exudative effusions are

Answer 26

protein-rich

and often cloudy due to the presence of white cells.

Question 27

Subcutaneous edema is important primarily

because

Answer 27

signals potential underlying cardiac or renal disease;
however, when significant, it can also impair wound healing or
the clearance of infections

Question 28

Pulmonary edema

Answer 28

that is most frequently seen in the setting of left
ventricular failure; it can also occur with renal failure, acute
respiratory distress syndrome (

Question 29

Pulmonary effusions often

Answer 29

accompany edema in the lungs and can further compromise gas
exchange by compressing the underlying pulmonary
parenchyma

Question 30

Peritoneal effusions (ascites

Answer 30

pulmonary
parenchyma. Peritoneal effusions (ascites) resulting most
commonly from portal hypertension are prone to seeding by
bacteria, leading to serious and sometimes fatal infections

Question 31

pulmonary
parenchyma. Peritoneal effusions (ascites) resulting most
commonly from portal hypertension are prone to seeding by
bacteria, leading to serious and sometimes fatal infections

Answer 31

Is life-threatening; if severe, brain substance can herniate
(extrude) through the foramen magnum, or the brain stem
vascular supply can be compressed. Either condition can injure
the medullary centers and cause death

Question 32

Hyperemia and Congestion

Answer 32

Hyperemia and congestion both stem from increased
blood volumes within tissues, but have different
underlying mechanisms and consequences.

Question 33

Hyperemia

Answer 33

active process in which arteriolar dilation (e.g., at sites of
inflammation or in skeletal muscle during exercise) leads to
increased blood flow. Affected tissues turn red (erythema)
because of increased delivery of oxygenated blood.

Question 34

Congestion

Answer 34

a passive process resulting from reduced outflow of blood from a
tissue. It can be systemic, as in cardiac failure, or localized, as in
isolated venous obstruction

Question 35

chronic passive

congestion

Answer 35

the associated chronic hypoxia may result in
ischemic tissue injury and scarring. In chronically congested
tissues, capillary rupture can also produce small hemorrhagic
foci; subsequent catabolism of extravasated red cells can leave
residual telltale clusters of hemosiderin-laden macrophages.

Question 36

Morphology Congested

tissues take on a

Answer 36

dusky
reddish-blue color (cyanosis)
due to red cell stasis and the
presence of deoxygenated
hemoglobin

Question 37

Microscopically,
acute pulmonary congestion
exhibits

Answer 37

engorged alveolar
capillaries, alveolar septal
edema, and focal intraalveolar
hemorrhage

Question 38

In chronic

pulmonary congestion

Answer 38

which
is often caused by congestive
heart failure, the septa are
thickened and fibrotic, and the
alveoli often contain numerous
hemosiderin-laden
macrophages called heart
failure cells.

Question 39

In acute hepatic

congestion,

Answer 39

the central vein
and sinusoids are distended.
Because the centrilobular area
is at the distal end of the
hepatic blood supply,
centrilobular hepatocytes may
undergo ischemic necrosis
while the periportal
hepatocytes—better
oxygenated because of
proximity to hepatic arterioles
—may only develop fatty
change.

Question 40

In chronic passive

hepatic congestion,

Answer 40

he
centrilobular regions are
grossly red-brown and slightly
depressed (because of cell
death) and are accentuated
against the surrounding zones
of uncongested tan liver
(nutmeg liver)

Question 41

Microscopically Hepatic Congestion

Answer 41

there is
centrilobular hemorrhage,
hemosiderin-laden
macrophages, and variable
degrees of hepatocyte dropout
and necrosis

Question 42

Hemostasis

Answer 42

Hemostasis can be defined simply as the process by which blood
clots form at sites of vascular injury. Hemostasis is essential for
life and is deranged to varying degrees in a broad range of
disorders, which can be divided into two groups

Question 43

hemorrhagic

disorders

Answer 43

characterized by excessive bleeding, hemostatic
mechanisms are either blunted or insufficient to prevent
abnormal blood loss.

Question 44

thrombotic disorders

Answer 44

blood
clots (often referred to as thrombi) form within intact blood
vessels or within the chambers of the heart. As is discussed in
Chapters 11 and 12, thrombosis has a central role in the most
common and clinically important forms of cardiovascular
disease.

Question 45

generalized activation of clotting sometimes paradoxically
produces bleeding due to the consumption of coagulation
factors

Answer 45

DIC

Question 46

Hemostasis v2`

Answer 46

Hemostasis is a precisely orchestrated process involving
platelets, clotting factors, and endothelium that occurs at
the site of vascular injury and culminates in the formation
of a blood clot, which serves to prevent or limit the extent
of bleeding

Question 47

Arteriolar vasoconstriction

Answer 47

occurs immediately and markedly

reduces blood flow to the injured area

Question 48

endothelin

Answer 48

a potent
endothelium-derived vasoconstrictor. This effect is transient,
however, and bleeding would resume if not for activation of
platelets and coagulation factors.

Question 49

Primary hemostasis

Answer 49

the formation of the platelet plug.
Disruption of the endothelium exposes subendothelial von
Willebrand factor (vWF) and collagen, which promote platelet
adherence and activation. Activation of platelets results in a
dramatic shape change (from small rounded discs to flat plates
with spiky protrusions that markedly increased surface area),
as well as the release of secretory granules. Within minutes the
secreted products recruit additional platelets, which undergo
aggregation to form a primary hemostatic plug

Question 50

Secondary hemostasis

Answer 50

deposition of fibrin. Tissue factor is also
exposed at the site of injury. Tissue factor is a membrane-bound
procoagulant glycoprotein that is normally expressed by
subendothelial cells in the vessel wall, such as smooth muscle
cells and fibroblasts. Tissue factor binds and activates factor
VII (see later), setting in motion a cascade of reactions that
culiminates in thrombin generation. Thrombin cleaves
circulating fibrinogen into insoluble fibrin, creating a fibrin
meshwork, and also is a potent activator of platelets, leading to
additional platelet aggregation at the site of injury. This
sequence, referred to as secondary hemostasis, consolidates
the initial platelet plug

Question 51

Clot stabilization and resorption.

Answer 51

Polymerized fibrin and
platelet aggregates undergo contraction to form a solid,
permanent plug that prevents further hemorrhage. At this
stage, counterregulatory mechanisms (e.g., tissue plasminogen
activator, t-PA) are set into motion that limit clotting to the site
of injury and eventually lead to clot resorption and
tissue repair

Question 52

Platelets

Answer 52

Platelets play a critical role in hemostasis by forming the
primary plug that initially seals vascular defects and by
providing a surface that binds and concentrates activated
coagulation factors.

Question 53

Their function depends on several
glycoprotein receptors, a contractile cytoskeleton, and two types
of cytoplasmic granules.

Answer 53

α-Granules, Dense (or δ) granules

Question 54

α-Granules

Answer 54

adhesion molecule
P-selectin on their membranes (Chapter 3) and contain proteins
involved in coagulation, such as fibrinogen, coagulation factor V,
and vWF, as well as protein factors that may be involved in
wound healing, such as fibronectin, platelet factor 4 (a heparinbinding chemokine), platelet-derived growth factor (PDGF), and
transforming growth factor-β.

Question 55

Dense (or δ) granules

Answer 55

contain
adenosine diphosphate (ADP) and adenosine triphosphate,
ionized calcium, serotonin, and epinephrine.
After a traumatic vascular injury, platelets encounter
constituents of the subendothelial connective tissue, such as
vWF and collagen. On contact with these proteins, platelets
undergo a sequence of reactions that culminate in the formation
of a platelet plug

Question 56

Platelet adhesion

Answer 56

mediated largely via interactions with vWF,
which acts as a bridge between the platelet surface receptor
glycoprotein Ib (GpIb) and exposed collagen (Fig. 4-5). Notably,
genetic deficiencies of vWF (von Willebrand disease, Chapter
14) or GpIb (Bernard-Soulier syndrome) result in bleeding
disorders, attesting to the importance of these factors.

Question 57

Platelets rapidly change shape following adhesion, being

converted from smooth discs to spiky

Answer 57

“sea urchins” with greatly
increased surface area. This change is accompanied by
alterations in glycoprotein IIb/IIIa that increase its affinity for
fibrinogen (see later), and by the translocation of negatively
charged phospholipids (particularly phosphatidylserine) to the
platelet surface. These phospholipids bind calcium and serve as
nucleation sites for the assembly of coagulation factor
complexes

Question 58

Secretion (release reaction) of granule contents

Answer 58

occurs along
with changes in shape; these two events are often referred to
together as platelet activation. Platelet activation is triggered
by a number of factors, including he coagulation factor
thrombin and ADP. Thrombin activates platelets through a
special type of G-protein–coupled receptor referred to as a
protease-activated receptor (PAR), which is switched on by a
proteolytic cleavage carried out by thrombin.

Question 59

ADP is a

component of dense-body granules; thus

Answer 59

platelet activation and
ADP release begets additional rounds of platelet activation, a
phenomenon referred to as recruitment. Activated platelets
also produce the prostaglandin thromboxane A2 (TxA2), a potent
inducer of platelet aggregation.

Question 60

Aspirin

Answer 60

inhibits platelet
aggregation and produces a mild bleeding defect by inhibiting
cyclooxygenase, a platelet enzyme that is required for TxA2
synthesis. Although the phenomenon is less well characterized,
it is also suspected that growth factors released from platelets
contribute to the repair of the vessel wall following injury.

Question 61

inherited

deficiency of GpIIb-IIIa results in a bleeding disorder called

Answer 61

Glanzmann thrombasthenia

Question 62

Coagulation Cascade

Answer 62

The coagulation cascade is series of amplifying enzymatic
reactions that leads to the deposition of an insoluble fibrin
clot.

Question 63

vitamin K

Answer 63

cofactor

Question 64

antagonized by drugs such

as coumadin

Answer 64

Anticoagulant

Question 65

The prothrombin time (PT) assay

Answer 65

assesses the function of the
proteins in the extrinsic pathway (factors VII, X, V, II, and
fibrinogen). In brief, tissue factor, phospholipids, and calcium
are added to plasma and the time for a fibrin clot to form is
recorded

Question 66

The partial thromboplastin time (PTT) assay

Answer 66

screens the
function of the proteins in the intrinsic pathway (factors XII, XI,
IX, VIII, X, V, II, and fibrinogen). In this assay, clotting of plasma
is initiated by addition of negative-charged particles (e.g.,
ground glass) that activate factor XII (Hageman factor)
together with phospholipids and calcium, and the time to fibrin
clot formation is recorded.

Question 67

Deficiencies of factors V, VII, VIII,

IX, and X are associated with

Answer 67

moderate to severe bleeding
disorders, and prothrombin deficiency is likely incompatible with
life.

Question 68

factor XI deficiency

Answer 68

only associated with mild
bleeding, and individuals with factor XII deficiency do not bleed
and in fact may be susceptible to thrombosis.

Question 69

The paradoxical
effect of factor XII deficiency may be explained by involvement
of factor XII in the

Answer 69

fibrinolysis pathway (discussed later); while
there is also some evidence from experimental models
suggesting that factor XII may promote thrombosis under
certain circumstances, the relevance of these observations to
human thrombotic disease remains to be determined.

Question 70

in vivo, factor VIIa/tissue factor complex is the

most important activator of

Answer 70

r IX and that factor IXa/factor

VIIIa complex is the most important activator of factor X

Question 71

Among the coagulation factors,________________ is the most
important, in that its various enzymatic activities control
diverse aspects of hemostasis and link clotting to
inflammation and repair

Answer 71

thrombin

Question 72

thrombin’s most important

activities are

Answer 72

• Conversion of fibrinogen into crosslinked fibrin
• Platelet activation
• Pro-inflammatory effects

Question 73

Conversion of fibrinogen into crosslinked fibrin

Answer 73

Thrombin
directly converts soluble fibrinogen into fibrin monomers that
polymerize into an insoluble clot, and also amplifies the
coagulation process, not only by activating factor XI, but also
be activating two critical co-factors, factors V and VIII. It also
stabilizes the secondary hemostatic plug by activating factor
XIII, which covalently cross-links fibrin.

Question 74

Platelet activation

Answer 74

Thrombin is a potent inducer of platelet
activation and aggregation through its ability to activate PARs,
thereby linking platelet function to coagulation

Question 75

Pro-inflammatory effects

Answer 75

PARs are also expressed on
inflammatory cells, endothelium, and other cell types (Fig. 4-8),
and activation of these receptors by thrombin is believed to
mediate proinflammatory effects that contribute to tissue repair
and angiogenesis.

Question 76

coagulation must be restricted to the site of vascular injury to prevent deleterious consequences. One limiting factor is

Answer 76

simple dilution

Question 77

requirement for

negatively charged phospholipids,

Answer 77

which, as mentioned, are
mainly provided by platelets that have been activated by contact
with subendothelial matrix at sites of vascular injury. However,
the most important counterregulatory mechanisms involve
factors that are expressed by intact endothelium adjacent to the
site of injury

Question 78

Activation of the coagulation cascade also sets into motion a

Answer 78

fibrinolytic cascade that limits the size of the clot and

contributes to its later dissolution

Question 79

Fibrinolysis

Answer 79

s
largely accomplished through the enzymatic activity of plasmin,
which breaks down fibrin and interferes with its polymerization.
An elevated level of breakdown products of fibrinogen (often
called fibrin split products), most notably fibrin-derived Ddimers, are a useful clinical markers of several thrombotic states

Question 80

Plasmin is generated by enzymatic catabolism

of the inactive circulating precursor

Answer 80

plasminogen, either by a
factor XII–dependent pathway (possibly explaining the
association of factor XII deficiency and thrombosis) or by
plasminogen activators.

Question 81

The most important plasminogen

activator is

Answer 81

t-PA it is synthesized principally by endothelium and
is most active when bound to fibrin. This characteristic makes tPA a useful therapeutic agent, since its fibrinolytic activity is
largely confined to sites of recent thrombosis

Question 82

Endothelium

Answer 82

The balance between the anticoagulant and procoagulant
activities of endothelium often determines whether clot
formation, propagation, or dissolution occurs

Question 83

Platelet inhibitory effects

Answer 83

An obvious effect of intact
endothelium is to serve as a barrier that shields platelets from
subendothelial vWF and collagen. However, normal
endothelium also releases a number of factors that inhibit
platelet activation and aggregation. Among the most important
are prostacyclin (PGI2), nitric oxide (NO), and adenosine
diphosphatase; the latter degrades ADP, already discussed as a
potent activator of platelet aggregation. Finally, endothelial
cells bind and alter the activity of thrombin, which is one of the
most potent activators of platelets.

Question 84

Anticoagulant effects

Answer 84

Normal endothelium shields coagulation
factors from tissue factor in vessel walls and expresses multiple
factors that actively oppose coagulation, most notably
thrombomodulin, endothelial protein C receptor, heparin-like
molecules, and tissue factor pathway inhibitor

Question 85

Thrombomodulin and endothelial protein C receptor bind

Answer 85

thrombin and protein C, respectively, in a complex on the

endothelial cell surface

Question 86

protein C

Answer 86

vitamin K–

dependent protease that requires a cofactor, protein S.

Question 87

Activated protein C/protein S complex is a potent inhibitor of

Answer 87

coagulation factors Va and VIIIa

Question 88

Heparin-like molecules

Answer 88

surface of endothelium bind and activate antithrombin III,

which then inhibits thrombin and factors IXa, Xa, XIa, and XIIa.

Question 89

Fibrinolytic effects

Answer 89

Normal endothelial cells synthesize t-PA,
already discussed, as a key component of the fibrinolytic
pathway.

Question 90

Hemorrhagic Disorders

Answer 90

Disorders associated with abnormal bleeding inevitably
stem from primary or secondary defects in vessel walls,
platelets, or coagulation factors, all of which must
function properly to ensure hemostasis.

Question 91

Diseases

associated with sudden, massive hemorrhage include

Answer 91

aortic
dissection in the setting of Marfan syndrome (Chapter 5), and
aortic abdominal aneurysm (Chapter 11) and myocardial
infarction

Question 92

Among the most common causes of

mild bleeding tendencies are inherited defects in

Answer 92

von Willebrand
factor (Chapter 14), aspirin consumption, and uremia (renal
failure); the latter alters platelet function through uncertain
mechanisms. Between these extremes lie deficiencies of
coagulation factors (the hemophilias, Chapter 14), which are
usually inherited and lead to severe bleeding disorders if
untreated.

Question 93

Defects of primary hemostasis

Answer 93

platelet defects or von
Willebrand disease) often present with small bleeds in skin or
mucosal membranes. These bleeds typically take the form of
petechiae, minute 1- to 2-mm hemorrhages (Fig. 4-11A), or
purpura, which are slightly larger (≥3 mm) than petechiae. It is
believed that the capillaries of the mucosa and skin are
particularly prone to rupture following minor trauma and that
under normal circumstances platelets seal these defects
virtually immediatel

Question 94

. Mucosal bleeding associated with defects

in primary hemostasis may also take the form of

Answer 94

epistaxis

(nosebleeds),

Question 95

gastrointestinal bleeding, or excessive

menstruation

Answer 95

menorrhagia

Question 96

A feared complication of very low

platelet counts thrombocytopenia

Answer 96

thrombocytopenia

Question 97

Defects of secondary hemostasis

Answer 97

(coagulation factor defects)
often present with bleeds into soft tissues (e.g., muscle) or
joint

Question 98

Bleeding into joints

Answer 98

hemarthrosis) following minor

trauma is particularly characteristic of hemophilia

Question 99

Generalized defects involving small vessels often present with

Answer 99

palpable purpura” and ecchymoses

Question 100

the volume of extravasated

blood is sufficient to create a palpable mass of blood known as

Answer 100

hematoma

Question 101

Purpura and ecchymoses are particularly
characteristic of systemic disorders that disrupt small blood
vessels

Answer 101

vasculitis

Question 102

blood vessel

fragility

Answer 102

amyloidosis, Chapter 6; scurvy,

Question 103

Rapid

loss of up to 20% of the blood volume may have

Answer 103

ittle impact in
healthy adults; greater losses, however, can cause hemorrhagic
(hypovolemic) shock

Question 104

Finally, chronic or recurrent external

blood loss

Answer 104

peptic ulcer or menstrual bleeding) causes iron
loss and can lead to an iron deficiency anemia. In contrast, when
red cells are retained (e.g., hemorrhage into body cavities or
tissues), iron is recovered and recycled for use in the synthesis
of hemoglobin.