43 - Hemodynamic Disorders Flashcards
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Review normal hemodynamics
- Hydrostatic pressure
- Oncotic pressure
- Lymphatics
On the arterial side of capillaries, hydrostatic (blood) pressure tends to force water across the capillary wall and into the interstitium, while on the venous side of capillaries,
oncotic pressure (created by circulating plasma proteins such as albumin) tends to draw water back into the capillary. Normally, the hydrostatic pressure is slightly greater than the osmotic pressure, resulting in a net movement of water into the interstitial space. This excess interstitial water is normally taken up by lymphatic vessels and ultimately returned to the intravascular space (via the thoracic duct). Under normal conditions, these forces are in homeostatic balance, so that there is not an accumulation of excess water in the interstitial space.
What is edema?
- Accumulation of extracellular fluid in tissues, organs,
or body cavities - Mechanisms
- Increased hydrostatic pressure
- Decreased oncotic pressure
- Increased capillary permeability
- Lymphatic obstruction
- Transudate versus exudate:
transudate is edema fluid that is primarily water and has a low specific gravity and a low protein and cell count. Transudates more commonly develop secondary to increased hydrostatic pressure or decreased oncotic pressure. In contrast, an exudate is edema fluid that has a higher specific gravity and higher protein and cell counts.
Exudates typically develop in association with inflammatory processes (the increased capillary permeability allows an influx of plasma proteins and inflammatory cells into the fluid).
What is the significance of edema?
Depends heavily on location:
Glomerular disease leading to proteinuria (and therefore decreased serum protein levels) and subsequent decreased oncotic pressure tends to be generalized and characteristically includes periorbital edema.
Pulmonary edema may develop secondary to a variety of conditions, but most commonly it is the result of congestive heart failure. Lungs involved by pulmonary edema are heavier than normal and, upon sectioning; there is a release of the free fluid contained within the alveolar spaces. Microscopically, pulmonary edema is characterized by the accumulation of eosinophilic, acellular material within the air (alveolar) spaces. The figure below shows the typical histologic appearance of pulmonary edema.
With cerebral edema, the brain gyri are swollen with corresponding narrowing of the sulci. The clinical
consequences of edema depend on the location and the severity of the fluid accumulation.
What is hyperemia?
- Increased blood flow into an area (active)
- Erythema (rubor)
- Inflammation
- Increased functional demand
What is congestion?
- Impaired venous drainage from an area (passive)
- Reddish-purple (more deoxygenated blood)
- Nutmeg liver
common clinical scenario in which congestion develops is congestive heart failure. With
congestive heart failure, there is decreased emptying of the heart and, as a result, and increase in
venous hydrostatic pressure (which impairs venous return), which is transmitted initially to the lungs
and then more systemically to the liver, the spleen, and peripheral soft tissues, causing congestion of
these tissues and organs. Not surprisingly, the phenomenon of congestion is frequently accompanied by
the development of edema, since both processes involve the same underlying pathophysiologic
mechanism.
can also cause iron buildup from digestion of accumulated erythrocytes
What is hemorrhage?
- Loss of blood from intravascular compartment
- Causes
- Trauma, inflammation, neoplasms, hypertension
- External versus internal
With hemorrhage, blood may be lost from the
body or it may accumulate within body tissues or cavities. An accumulation of blood within tissues is
referred to as a hematoma.
What are the classifications of hemorrhage?
Three somewhat distinct terms are utilized to describe skin, soft tissue, and mucosal hemorrhages and these include: 1) petechiae, which are small pinpoint (1-2 mm)
hemorrhages, 2) purpura, which is a slightly larger (>3mm) hemorrhages, and 3) an ecchymosis, which is
a larger, deeper skin and soft tissue hemorrhage (hematoma). The composite figure below
demonstrates mucosal petechiae of the palate (upper left), purpura (upper right), ecchymosis (lower left), and a hematoma (lower right).
What is the clinical significance of hemorrhage?
- Amount and duration
- Hypovolemia results in Impaired perfusion → Shock
- Iron deficiency
- Location
Hemorrhage may also occur into a body space or cavity is named accordingly (e.g. hemothorax,
hemopericardium, hemoperitoneum, or hemarthrosis). The clinical significance of hemorrhage depends
on the amount, rate, and location of the bleed. Sudden loss of a significant amount of blood (>20% of
blood volume) may interfere with the ability to adequately perfuse tissues throughout the body leading
to hypovolemic shock (see below). The same amount of bleeding may have vastly different clinical
outcomes depending on the site of bleeding. Specifically, intracranial hemorrhage may create a mass
effect, which may then displace (herniate) vital brain structures and lead to the death of the patient.
Patients who have sustained significant internal hemorrhage may actually develop jaundice as a result of
hemoglobin breakdown into bilirubin. Chronic loss of blood from the body (e.g. gastrointestinal
bleeding secondary to an ulcer or neoplasm) may be associated with depletion of iron and subsequent
development of iron deficiency anemia. This is in contrast to internal bleeding, in which the iron
contained in the hemoglobin of the extravasated red cells can be recycled.
What is thrombosis?
- Inappropriate clot formation
- Mechanisms (Virchow’s triad):
- Endothelial injury (arterial)
- Alterations in blood flow (venous) (stasis or turbulence)
- Hypercoagulable state (arterial, venous)
Endothelial cell injury or disruption is the most important precipitating cause for thrombus formation in
the arterial system. Normally, endothelial cells, through production of a variety of anticoagulant
molecules (prostacyclin, nitric oxide, and heparin-like molecules), provide a surface lining all blood
vessels that does not favor clot formation. With endothelial cell injury, production of these factors may
be decreased, thereby diminishing the normal antithrombotic properties of the endothelial layer.
High pressure or turbulent blood flow, as noted above, may lead to endothelial cell injury. Conversely,
vascular stasis is the most important precipitating factor in the development of venous thrombosis.
Alterations in blood flow disrupt the normal laminar flow pattern of blood (plasma peripherally with
platelets and other blood cells centrally) and create a scenario in which platelets and coagulation
proteins have more of a sustained close association with the vessel wall, a situation that favors clot
formation. Prolonged best rest or immobility leads to venous stasis (especially in the lower extremities)
and an increased risk for thrombosis.
Hypercoagulability (thrombophilia) is another predisposing cause for the development of either arterial
or venous thrombosis. A hypercoagulable state may be secondary to an inherited mutation involving a
normal coagulation protein (factor V, prothrombin) or a protein that normally regulates the coagulation
cascade (antithrombin, protein C, or protein S).
What are the morphological features of a thrombus?
- Sequential growth (lines of Zahn)
- White thrombi (arterial) versus red thrombi (venous)
- Arterial thrombi – anywhere - Mural thrombi
- Venous thrombi – deep leg veins
- Microcirculatory thrombi (DIC)
The developing thrombus is initially anchored to the vessel wall and then may subsequently expand in size. Venous thrombi tend to grow in the direction of blood flow (toward the heart). The growth of a thrombus occurs in layers that generally alternate between platelets/fibrin and red blood cells, creating so-called lines of Zahn.
Arterial thrombi have a tendency to be occlusive in nature leading to compromised perfusion of tissues supplied by the thrombosed vessel.
Venous thrombi are usually large and occlusive and tend to
contain a greater number of red cells.
disseminated intravascular coagulation (DIC), which results from inappropriate systemic activation of the coagulation cascade and platelets. The end result is the formation of
microthrombi in capillaries throughout the body, which leads to consumption of platelets and coagulation proteins and paradoxically makes bleeding more likely.
What are the fates of thrombi?
- Dissolution (fibrinolysis)
- Propagation
- Embolization
- Organization
The most favorable outcome of thrombosis is complete and early dissolution of the thrombus through activation of the fibrinolytic pathway (plasmin). With time, however, the fibrin within a thrombus becomes cross-linked, rendering it more resistant to the action of plasmin. As noted above, thrombi tend to grow or propagate over time.
The expanding portion of a thrombus is generally poorly attached and prone to fragmentation and
embolization. Old thrombi can become organized and even recanalized by an ingrowth of endothelial cells, fibroblasts, and smooth muscle cells.
What is embolization?
- Passage of material from one point in the circulatory
system to another - Occlusion of the distal vessel → ischemia/necrosis
- Most often thromboemboli
venous thrombi give rise to emboli that travel to the lungs and this process is referred to as pulmonary embolism
A large thromboembolus that lodges in the mainstem pulmonary artery and blocks both the right and left main pulmonary artery is called a saddle embolus. Saddle emboli may completely occlude blood flow to the lungs and as a result may lead to rapid clinical deterioration and sudden death. The figure below demonstrates the appearance of a fatal saddle embolus.
What are other types of emboli?
At high pressures, increased amounts of nitrogen gas (from the air) become dissolved in the blood and in tissues. Rapid depressurization causes the dissolved nitrogen gas to come out of solution and form gas bubbles, which can cause
musculoskeletal symptoms (joint and muscle pain) and respiratory distress secondary to embolization of
the pulmonary vasculature.
Embolism of amniotic fluid, which may be a complication of labor and delivery, occurs when amniotic
fluid including exfoliated fetal squamous epithelial cells enter the uterine veins and then embolize
systemically.
What is an infarction?
- Irreversible cell injury/cell death secondary to
ischemia (arterial occlusion) - Causes
- Thrombosis, embolization, extrinsic compression,
torsion
An infarct refers to a localized area of tissue necrosis secondary to ischemia.
What is the morphology of infarction?
- Red (hemorrhagic) infarct
- Loose tissues, dual blood supply, previous
congestion, sudden reperfusion
the infarct occurs in loose tissues that allow extravasation of red cells (e.g. the lung), 2) the infarcted tissue has a normal dual blood supply that allow inflow of blood to the infarct from a second source( e.g. lung and small intestine), 3) the infarct occurs in previously congested tissue causing poor venous outflow, or 4) there is sudden reperfusion of previously infarcted tissue.
- White (anemic) infarct
-white infarcts occur following arterial
occlusion in solid organs (e.g. heart, spleen, or kidney), which have a single blood supply. - Wedge-shaped
-Infarcts often appear wedge-shaped with the
apex of the wedge pointing to the occluded vessel. - Coagulative necrosis (except brain)
-microscopically infarcts are characterized by coagulative necrosis (the notable exception being the brain, which will demonstrate liquefactive necrosis).
What is shock?
- Profound circulatory disturbance with systemic
hypotension and global hypoperfusion of tissues
- Mechanisms:
- Hypovolemic (decreased blood volume)
- Cardiogenic (pump failure)
- Septic (infectious)
- Neurogenic (brain/spinal cord injury)
- Anaphylactic (severe hypersensitivity reaction)
Cardiogenic shock occurs when the heart ceases to effectively function as a circulatory pump (e.g. myocardial infarction, arrhythmia, pulmonary embolism, etc.).
Hypovolemic shock results from an inadequate circulating blood/plasma volume (e.g. severe hemorrhage, severe burns, or excess fluid loss).
Septic shock results from generalized vasodilation and peripheral pooling of blood (which effectively reduces the circulating blood volume) that occurs as a reaction to an infectious process (often bacterial or less commonly fungal infections).
Occasionally, shock develops as the result of a severe brain or spinal cord injury (neurogenic shock), which leads to loss of vascular tone and peripheral pooling of blood
severe allergic reaction (anaphylactic shock)
1) an early non-progressive stage, in
which compensatory mechanisms are utilized to maintain perfusion of vital organs, 2) a progressive
stage characterized by systemic hypoperfusion and further circulatory and metabolic derangements
(e.g. metabolic acidosis), and 3) a final and irreversible stage characterized by progressive organ
dysfunction, from which the body cannot recover. With all forms of shock, a common final pathway is a
global impairment of oxygen delivery to tissues and organs throughout the body.
What is the morphology of shock?
- Global hypoxic injury (multi-system organ failure)
- Watershed infarcts (brain)
- Shock lung (alveolar damage, hyaline membranes)
- Tubular necrosis (kidneys)
- Adrenal hemorrhage (Waterhouse-Friderichsen
syndrome)
Certain regions within the brain are especially vulnerable to hypoxic stress, including cells at the junctions of major arterial circulation patterns (watershed infarct). Cardiac myocytes may demonstrate coagulative necrosis. Within the lungs, as a result of endothelial and epithelial cell injury, a pattern of diffuse alveolar damage (shock lung) is observed, characterized initially by edema and the formation of eosinophilic hyaline membranes (composed of plasma proteins and debris from necrotic cells) that line the alveolar spaces. (pink pic)
Within the kidneys, the epithelial cells of the proximal convoluted tubules are especially vulnerable to hypoxia, resulting in acute tubular necrosis (coagulative necrosis). The epithelial lining of the intestines similarly undergo ischemic necrosis. In any form of severe stress, including shock, lipid depletion of the cortical region of the adrenal glands may be observed as well as intra-adrenal hemorrhage and necrosis. This latter feature may be especially conspicuous in patients with an overwhelming Neisseria meningitidis (meningococcus) sepsis and this condition is called Waterhouse-Friderichson syndrome. The figure below compares the morphology of a normal adrenal gland (left) to an adrenal from a patient with meningococcal sepsis (right). Note the extensive adrenal hemorrhage on the right. (white black bottom slide)
