Hemodynamic Dysfunction ‫م نور ناطق‬.

‫م‬
Edema
Sixty percent of lean body weight is water,2/3 intracellular and 1/3 is in
extracellular which is mostly interstitial fluid, only 5% of total body
water is in blood plasma.

Edema: - This is an abnormal accumulation of fluid in interstitial tissue

spaces or body cavities.
A. Causes of edema
1. Increased hydrostatic pressure is exemplified by CHF.
a. Right-sided heart failure results in peripheral edema.
b. Left-sided heart failure results in pulmonary edema.
2. Increased capillary permeability occurs in inflammation or with
injury to capillary endothelium, as may occur in burn injury.
3. Decreased oncotic pressure is from hypoalbuminemia caused by:
a. Increased loss of protein, for example, by renal loss in the nephrotic
syndrome
b. Decreased production of albumin in cirrhosis of the liver
4. Increased sodium retention can occur as either a primary or
secondary phenomenon.
a. Primary sodium retention, associated with renal disorders
b. Secondary sodium retention, such as occurs in CHF
(1) Decreased cardiac output results in decreased renal blood flow, which
activates
the renin-angiotensin system.
(2) In turn, this activates aldosterone production, with resultant retention
of sodium
and water.
5. Blockage of lymphatics results in lymphedema.
Note:
A transudate: occurs with volume or pressure overload, or under
conditions of reduced plasma protein; typically it is protein_poor with
specific gravity less than 1.012
An exudate it is protein rich with specific gravity greater than 1.020, it
occurs due to increased vascular permeability in inflammation.
Hemorrhage:-
A. general considerations
1. Hemorrhage is the extravasation of blood from the vasculature into
surrounding tissues, a hollow organ or body cavity, or to the outside.
2. Hemorrhage is most often caused by trauma.

3. Hemorrhagic diatheses increased tendency to hemorrhage (even with in

significant injury)
B. Hematoma. This localized hemorrhage occurs within a tissue or
organ, can be relatively in significant (e.g., bruise) or can be massive
bleeding and cause death (e.g., massive retroperitoneal hematoma).
C. Hemothorax, hemopericardium, hemoperitoneum, and
hemarthrosis. Hemorrhage may occur in the pleural cavity, pericardial
sac, peritoneal cavity, or a synovial space, respectively.
D. Petechial hemorrhages, petechiae, or purpura. These small,
punctate hemorrhages occur in the skin, mucous membranes, or serosal
surfaces.
E. ecchymosis. This diffuse hemorrhage is usually in skin and
subcutaneous tissue.

Hyperemia: - a localized increase in the volume of blood in capillaries

and small vessels.

A. active hyperemia. The cause is localized arteriolar dilation (e.g.,

blushing, inflammation).
B. Passive congestion (passive hyperemia). The cause is obstructed
venous return or increased back pressure from congestive heart failure
(CHF).
1. Acute passive congestion occurs in shock, acute inflammation, or
sudden right-sided heart failure.
2. Chronic passive congestion
a. chronic passive congestion of the lung is caused most often by left-
sided heart failure or mitral stenosis.
(1) Congestion and distention of alveolar capillaries leads to capillary
rupture and passage of red cells into the alveoli.
(2) Phagocytosis and degradation of red cells result in intra-alveolar
hemosiderinladen macrophages called heart failure cells.
(3) In long-standing congestion, fibrosis of interstitium and hemosiderin
deposition results in brown induration of the lung.

Infarction: -
A. Definition. Infarction is localized area of ischemic cell necrosis in a
living organ or tissue, result from sudden reduction or cessation of its
arterial blood supply or occasionally its venous drainage.

B. Anemic infarcts
1. These infarcts are white or pale infarcts.
2. They are usually caused by arterial occlusions in the heart, spleen,
and kidney.
C. Hemorrhagic infarcts
1. These infarcts are red infarcts, in which red cells ooze into the
necrotic area.
2. They occur characteristically in the lung and gastrointestinal tract as
the result of arterial occlusion. These sites are loose, well-vascularized
tissues with redundant arterial blood supplies (in the lung, from the
pulmonary and bronchial systems; in the gastrointestinal tract, from
multiple anastomoses between branches of the mesenteric artery), and a
hemorrhage into the infarct occurs from the no obstructed portion of
the vasculature.
3. They can also be caused by venous occlusion. This is an important
contribution to infarcts associated with volvulus, incarcerated hernias,
and postoperative adhesions.

Factors that influence the development of an infract

1- Nature of the vascular supply.

2- Rate of the development of occlusion.
3- Oxygen content of blood
4- Vulnerability of tissue to hypoxia.

Thrombosis: - intravascular coagulation of blood, often causing

significant interruption of blood flow. Pathologically predisposed by
many conditions, including venous stasis, usually from immobilization;
CHF; polycythemia; sickle cell disease; visceral malignancies; and the
use of oral contraceptives, especially in association with cigarette
smoking.
A. Thrombogenesis. This process results from the interaction of
1-platelets, 2-damaged endothelial cells(vascular wall), and 3-the
coagulation cascade.
1. Platelets
a. Platelet functions
(1) Maintain the physical integrity of the vascular endothelium
(2) Participate in endothelial repair through the contribution of
platelet-derived
growth factor (PDGF)
(3) Form platelet plugs
(4) Promote the coagulation cascade through the platelet
phospholipid complex
b. reactions involving platelets
(1) adhesion
(a) Vessel injury exposes subendothelial collagen, leading to
platelet adhesion(adherence to the subendothelial surface).
(b) Interaction of specific platelet-surface glycoprotein
receptors and subendothelial collagen is mediated by von
Willebrand factor.
(2) release reaction. Soon after adhesion, platelets release
adenosine diphosphate (ADP), histamine, serotonin, PDGF, and
other platelet granule constituents.
(3) activation of coagulation cascade. Conformational change in
the platelet membrane makes the platelet phospholipid complex
available, thus contributing to
the activation of the coagulation cascade, leading to the formation
of thrombin.
(4) arachidonic acid metabolism. Arachidonic acid, provided by
activation of the platelet membrane phospholipase, proceeds
through the cyclooxygenase pathway to the production of
thromboxane a2 (txa2). Platelet TxA2 is a potent vasoconstrictor
and platelet aggregant. The inhibition of cyclooxygenase by low-
dose aspirin is the basis of aspirin therapy for prevention of
thrombotic disease.
(5) Platelet aggregation
(a) Platelets stick to each other (as contrasted to adhesion, the
adherence of platelets to the underlying subendothelium).
 (b) Additional platelets are recruited from the circulation to
produce the initial
hemostatic platelet plug.
(c) The process is mediated by the glycoprotein IIb-IIIa
complex on the surface of the platelets that is required for the
linking of platelets by fibrinogen
bridges.
(d) Agonists that promote aggregation include aDP, thrombin,
and txa2, as well as collagen, epinephrine, and platelet-
activating factor, derived from the granules of basophils and mast
cells.
(6) stabilization of the platelet plug. Fibrinogen bridges bind the
aggregated platelets together. The platelet mass is stabilized by
fibrin.
(7) Limitation of platelet plug formation. Prostacyclin (PGI2),
another product of the cyclooxygenase pathway, is synthesized by
endothelial cells. Endothelial PGI2 is antagonistic to platelet TxA2
and limits further platelet aggregation. Fibrin degradation products
are also inhibitors of platelet aggregation.

2. Endothelial cells
a. These cells are resistant to the thrombogenic influence of platelets and
coagulation proteins. Intact endothelial cells act to modulate several
aspects of hemostasis and oppose coagulation after injury by
thromboresistance.
b. Some functions of endothelial cells include:
(1) Producing heparin-like molecules, endothelial proteoglycans that
activate antithrombin III, which neutralizes thrombin and other
coagulation factors, including factors IXa and Xa
(2) Secreting plasminogen activators, such as tissue plasminogen
activator (TPA)
(3) Degrading ADP
(4) Taking up, inactivating, and clearing thrombin
(5) Synthesizing thrombomodulin, a cell-surface protein that binds
thrombin and
converts it to an activator of protein C, a vitamin K-dependent plasma
protein.
Activated protein C (APC) cleaves factors Va and VIIIa, thus inhibiting
coagulation.
(6) Synthesizing protein s, a cofactor for APC
(7) Synthesizing and releasing PGI2
(8) Synthesizing and releasing nitric oxide, which has actions similar to
those of PGI2

3. Coagulation cascade. This has been classically described as following

two distinct, but interconnected, pathways.
a. extrinsic pathway of coagulation is initiated by tissue factor, which
activates factor VII and forms a tissue factor–factor VIIa complex.

b. Intrinsic pathway of coagulation involves the activation of all

clotting factors with the exception of factors VII and XIII.

B. fibrinolysis (thrombus dissolution). This is concurrent with

thrombogenesis and modulates coagulation. It restores blood flow in
vessels occluded by a thrombus and facilitates healing after inflammation
and injury.
1. The proenzyme plasminogen is converted by proteolysis to plasmin,
the most important fibrinolytic protease.
2. Plasmin splits fibrin.
3. It is a classic teaching that factor XII to XIIa activation links the
fibrinolytic system,coagulation system, complement system, and kinin
system.

4. Disseminated intravascular coagulation (DIC)

DIC is both a prothrombotic and antithrombotic disorder characterized
by widespread thrombosis and hemorrhage resulting from the
consumption of platelets and coagulation factors.

5. Heparin-induced thrombocytopenia (HIT) syndrome

a. This syndrome is characterized by heparin-induced thrombocytopenia
(and thrombosis) and is a consequence of therapy with high-molecular-
weight heparin.
b. There are two types:
(1) type I HIT results in a mild to moderate drop in platelets. It occurs
in about 5% of heparinized platelets and can appear within a day of
heparinization. It is not
immune-mediated and is not a contraindication to future heparin use.
(2) type II HIT leads to a severe drop in platelets (often <50% of
baseline) and imparts a high risk of thrombosis. It usually manifests 5 to
10 days after heparin therapy and occurs in ∼1% of heparinized patients.
It is thought to be caused by antibodies to the complex of heparin and
platelet factor 4 (Pf4). However, identification of anti-PF4 antibodies is
not diagnostic of Type II HIT as they can be seen in non-
thrombocytopenic heparinized patients. The gold standard for diagnosis is
the serotonin-release assay, although this test is rarely used in practice
and presumptive diagnosis is often made based on clinical factors and the
presence of PF4 antibodies. Once Type II HIT has been diagnosed,
further heparin treatment is contraindicated.

C. Morphologic characteristics of thrombi and clots

1. arterial thrombi
a. These thrombi are formed in areas of active blood flow.
b. When mature, they demonstrate alternate dark gray layers of platelets
interspersed with lighter layers of fibrin. This layering results in the lines
of Zahn.
c. Eventually they liquefy and disappear or are organized with fibrous
tissue formation. Recanalization, new blood vessel formation within a
thrombus, restores blood flow.
2. Venous thrombi (phlebothrombosis)
a. These thrombi are formed in areas of less active blood flow, most
often in the veins of the lower extremities and in the periprostatic or
other pelvic veins.
b. They are predisposed by venous stasis, with a high incidence
occurring in hospitalized patients on bed rest.
c. They are dark red with a higher concentration of red cells than
arterial thrombi. Lines of Zahn are not prominent or are absent.
d. They are often associated with concurrent venous inflammatory
changes.
Inflammation of veins with thrombus formation is referred to
asthrombophlebitis.
3. Postmortem clots
a. These clots appear soon after death and are not true thrombi. In
contrast to true
thrombi, they are not attached to the vessel wall.
b. Settling of red cells results in a two-layered appearance: currant jelly
appearance in the red cell-rich lower layer and a chicken fat
appearance in the cell-poor upper layer.