Edema and Effusion 1 Flashcards
1
Q
Edema
A
Disorders that perturb cardiovascular, renal, or hepatic
function are often marked by the accumulation of fluid in
tissues
2
Q
(effusions
A
body cavities
3
Q
Noninflammatory edema
and effusions are common in many diseases
A
heart
failure, liver failure, renal disease, and severe nutritional
disorders
4
Q
Increased Hydrostatic Pressure
A
Increases in hydrostatic pressure are mainly caused by
disorders that impair venous return.
5
Q
If the impairment is
localized
A
DVT
6
Q
Conditions leading to systemic increases in venous
pressure
A
CHF
7
Q
Increased Hydrostatic Pressure
A
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.
8
Q
Hypoalbunemia
A
end-stage cirrhosis,
protein malnutrition
9
Q
An important
cause of albumin loss is
A
nephrotic syndromein
which albumin leaks into the urine through abnormally
permeable glomerular capillaries.
10
Q
reduced
plasma osmotic pressure leads in a stepwise fashion to edema,
reduced intravascular volume
A
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.
11
Q
Sodium and Water Retention
A
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)
12
Q
Salt retention occurs
A
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.
13
Q
In early
heart failure, this response is beneficial,
A
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.
14
Q
Lymphatic Obstruction
A
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
15
Q
LO example
A
Filariasis
16
Q
Morphology Edema is easily
recognized grossly; microscopically,
A
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.
17
Q
Subcutaneous edema
A
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.
18
Q
Finger pressure over markedly
edematous subcutaneous
tissue displaces the interstitial
fluid and leaves a depression,
A
pitting edema
19
Q
Edema resulting from renal dysfunction often
appears initially in
A
body containing loose
connective tissue, such as the eyelids, Periorbital Edema
20
Q
pulmonary edema,
A
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.
21
Q
Brain edema
A
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
22
Q
Effusions involving the pleural cavity
A
(hydrothorax
23
Q
pericardial cavity
A
hydropericardium
24
Q
peritoneal cavity
A
hydroperitoneum or ascites
25
Transudative effusions are
| typically
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.
26
exudative effusions are
protein-rich
| and often cloudy due to the presence of white cells.
27
Subcutaneous edema is important primarily
| because
signals potential underlying cardiac or renal disease;
however, when significant, it can also impair wound healing or
the clearance of infections
28
Pulmonary edema
that is most frequently seen in the setting of left
ventricular failure; it can also occur with renal failure, acute
respiratory distress syndrome (
29
Pulmonary effusions often
accompany edema in the lungs and can further compromise gas
exchange by compressing the underlying pulmonary
parenchyma
30
Peritoneal effusions (ascites
pulmonary
parenchyma. Peritoneal effusions (ascites) resulting most
commonly from portal hypertension are prone to seeding by
bacteria, leading to serious and sometimes fatal infections
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
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
32
Hyperemia and Congestion
Hyperemia and congestion both stem from increased
blood volumes within tissues, but have different
underlying mechanisms and consequences.
33
Hyperemia
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.
34
Congestion
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
35
chronic passive
| congestion
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.
36
Morphology Congested
| tissues take on a
```
dusky
reddish-blue color (cyanosis)
due to red cell stasis and the
presence of deoxygenated
hemoglobin
```
37
Microscopically,
acute pulmonary congestion
exhibits
engorged alveolar
capillaries, alveolar septal
edema, and focal intraalveolar
hemorrhage
38
In chronic
| pulmonary congestion
```
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.
```
39
In acute hepatic
| congestion,
```
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.
```
40
In chronic passive
| hepatic congestion,
```
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)
```
41
Microscopically Hepatic Congestion
```
there is
centrilobular hemorrhage,
hemosiderin-laden
macrophages, and variable
degrees of hepatocyte dropout
and necrosis
```
42
Hemostasis
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
43
hemorrhagic
| disorders
characterized by excessive bleeding, hemostatic
mechanisms are either blunted or insufficient to prevent
abnormal blood loss.
44
thrombotic disorders
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.
45
generalized activation of clotting sometimes paradoxically
produces bleeding due to the consumption of coagulation
factors
DIC
46
Hemostasis v2`
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
47
Arteriolar vasoconstriction
occurs immediately and markedly
| reduces blood flow to the injured area
48
endothelin
a potent
endothelium-derived vasoconstrictor. This effect is transient,
however, and bleeding would resume if not for activation of
platelets and coagulation factors.
49
Primary hemostasis
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
50
Secondary hemostasis
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
51
Clot stabilization and resorption.
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
52
Platelets
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.
53
Their function depends on several
glycoprotein receptors, a contractile cytoskeleton, and two types
of cytoplasmic granules.
α-Granules, Dense (or δ) granules
54
α-Granules
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.
55
Dense (or δ) granules
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
56
Platelet adhesion
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.
57
Platelets rapidly change shape following adhesion, being
| converted from smooth discs to spiky
“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
58
Secretion (release reaction) of granule contents
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.
59
ADP is a
| component of dense-body granules; thus
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.
60
Aspirin
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.
61
inherited
| deficiency of GpIIb-IIIa results in a bleeding disorder called
Glanzmann thrombasthenia
62
Coagulation Cascade
The coagulation cascade is series of amplifying enzymatic
reactions that leads to the deposition of an insoluble fibrin
clot.
63
vitamin K
cofactor
64
antagonized by drugs such
| as coumadin
Anticoagulant
65
The prothrombin time (PT) assay
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
66
The partial thromboplastin time (PTT) assay
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.
67
Deficiencies of factors V, VII, VIII,
| IX, and X are associated with
moderate to severe bleeding
disorders, and prothrombin deficiency is likely incompatible with
life.
68
factor XI deficiency
only associated with mild
bleeding, and individuals with factor XII deficiency do not bleed
and in fact may be susceptible to thrombosis.
69
The paradoxical
effect of factor XII deficiency may be explained by involvement
of factor XII in the
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.
70
in vivo, factor VIIa/tissue factor complex is the
| most important activator of
r IX and that factor IXa/factor
| VIIIa complex is the most important activator of factor X
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
thrombin
72
thrombin's most important
| activities are
* Conversion of fibrinogen into crosslinked fibrin
* Platelet activation
* Pro-inflammatory effects
73
Conversion of fibrinogen into crosslinked fibrin
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.
74
Platelet activation
Thrombin is a potent inducer of platelet
activation and aggregation through its ability to activate PARs,
thereby linking platelet function to coagulation
75
Pro-inflammatory effects
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.
76
coagulation must be restricted to the site of vascular injury to prevent deleterious consequences. One limiting factor is
simple dilution
77
requirement for
| negatively charged phospholipids,
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
78
Activation of the coagulation cascade also sets into motion a
fibrinolytic cascade that limits the size of the clot and
| contributes to its later dissolution
79
Fibrinolysis
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
80
Plasmin is generated by enzymatic catabolism
| of the inactive circulating precursor
plasminogen, either by a
factor XII–dependent pathway (possibly explaining the
association of factor XII deficiency and thrombosis) or by
plasminogen activators.
81
The most important plasminogen
| activator is
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
82
Endothelium
The balance between the anticoagulant and procoagulant
activities of endothelium often determines whether clot
formation, propagation, or dissolution occurs
83
Platelet inhibitory effects
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.
84
Anticoagulant effects
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
85
Thrombomodulin and endothelial protein C receptor bind
thrombin and protein C, respectively, in a complex on the
| endothelial cell surface
86
protein C
vitamin K–
| dependent protease that requires a cofactor, protein S.
87
Activated protein C/protein S complex is a potent inhibitor of
coagulation factors Va and VIIIa
88
Heparin-like molecules
surface of endothelium bind and activate antithrombin III,
| which then inhibits thrombin and factors IXa, Xa, XIa, and XIIa.
89
Fibrinolytic effects
Normal endothelial cells synthesize t-PA,
already discussed, as a key component of the fibrinolytic
pathway.
90
Hemorrhagic Disorders
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.
91
Diseases
| associated with sudden, massive hemorrhage include
aortic
dissection in the setting of Marfan syndrome (Chapter 5), and
aortic abdominal aneurysm (Chapter 11) and myocardial
infarction
92
Among the most common causes of
| mild bleeding tendencies are inherited defects in
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.
93
Defects of primary hemostasis
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
94
. Mucosal bleeding associated with defects
| in primary hemostasis may also take the form of
epistaxis
| (nosebleeds),
95
gastrointestinal bleeding, or excessive
| menstruation
menorrhagia
96
A feared complication of very low
| platelet counts thrombocytopenia
thrombocytopenia
97
Defects of secondary hemostasis
(coagulation factor defects)
often present with bleeds into soft tissues (e.g., muscle) or
joint
98
Bleeding into joints
hemarthrosis) following minor
| trauma is particularly characteristic of hemophilia
99
Generalized defects involving small vessels often present with
palpable purpura” and ecchymoses
100
the volume of extravasated
| blood is sufficient to create a palpable mass of blood known as
hematoma
101
Purpura and ecchymoses are particularly
characteristic of systemic disorders that disrupt small blood
vessels
vasculitis
102
blood vessel
| fragility
amyloidosis, Chapter 6; scurvy,
103
Rapid
| loss of up to 20% of the blood volume may have
ittle impact in
healthy adults; greater losses, however, can cause hemorrhagic
(hypovolemic) shock
104
Finally, chronic or recurrent external
| blood loss
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.
