CLS 3223 ADVANCED HEMATOLOGY DISORDERS

HEMODYNAMICS AND PATHOLOGY

This part of the teaching syllabus discusses the body fluid compartments and the effects of accumulation or loss of fluids in each of the compartments. The narrative in these classroom lectures for CLS 3223 Advanced Hematology Disorders arranged in objectives. All objectives are listed in the cognitive unless indicated otherwise. The student at the end of the instructional period is responsible for meeting these objectives by achieving a score of 70% or better on all problem sets, case studies, major exams, quizzes, and library assignments.

Objectives are listed in numerical order. The student, upon completion of the classroom component of this instructional syllabus will be responsible to successfully:

01    BRIEFLY DESCRIBE WATER AND BODY COMPARTMENT.

The body, by weight is about 60% water, a major component of the body.  Note that an infant is comprised of about 70% water and contributes to the difference in normal laboratory values between infants and adults.  This water (although it is found inside and outside of the cells)  is distributed in three compartments designated as extracellular, intracellular and plasma. Plasma (with its water content) is the fluid portion of the blood and makes up approximately 5% of the total body weight. The extracellular compartment is the intracellular spaces of the body and makes up about 20% of the total body weight.  It is here that that the blood or intravascular fluid is found.  The third region, the intracellular compartment, with its water makes up approximately 35% of the body weight. When water redistributes itself and changes its normal physiological volumes, then over-hydration or dehydration occurs.

For the human individual to be healthy, the amount of water loss should be balanced by an equivalent intake of water.

02   DEFINE EDEMA AND DISTINGUISH BETWEEN LOCAL AND GENERALIZED EDEMA.

Edema is the presence of excess fluid in the body cavities and/or interstitial spaces of the body. If the edema is observed in the tissues or organs it is designated as local edema. For example if the accumulated fluid occurs in the brain, then it is called cerebral edema. Excess fluid in the lungs is referred to as pulmonary edema. An appendage may demonstrate edema in the extremities and when this occurs it usually caused by some form of obstruction of the veins or lymph vessels. A burn patient will usually experience local edema because the vasculature has been heat damaged and the permeability disrupted.

Generalized edema is that which affects the viscera and/or the skin of the trunk and lower extremities. This category of edema is most often due to heart failure, but has been observed in renal failure and cirrhosis of the liver. When generalized edema becomes extreme, it is designated as anasarca. This is a profuse accumulation of fluid in the viscera, body cavities, and subcutaneous tissues.

03   DISCUSS THE FOLLOWING FORMS OF EDEMA.

HYDROSTATIC EDEMA. The rate of formation of the edematous fluid is due to the increase in arterial blood pressure. The absence of opposing forces to this increased hydrostatic pressure causes increased transmembranous fluid movement. This type of edema is seen in lungs where there is left ventricular failure with increased back-pressure in the pulmonary arteries. There is a consequential decrease in right ventricular function which compounds the problem.  When this happens, fluid can be forced into the alveoli causing impaired respiratory function.  Another example is when there is portal vein obstruction in a cirrhotic liver causing ascites.

HYPERVOLEMIC EDEMA. This is a condition that results because of water and sodium retention. During normal kidney function, there is a normal regulation of renin, which ultimately stops or causes the release of aldosterone. Aldosterone causes the retention of sodium. Sodium is the cation that determines the osmolarity of extracellular fluid. If sodium ion is present, water is retained. If sodium ion is excreted, water is also excreted. For example, if the patient suffers from chronic heart disease characterized by hypovolemia and decreased hydrostatic pressure, the kidney is hypoperfused with blood, causing the increased release of renin which causes increased production and release of aldosterone. There is an increased renal retention of sodium and water.   This condition is associated with kidney failure, pregnancy, and heart failure.

If a patient has been diagnosed with chronic heart failure and edema is present, the edema will be most prominent in the lower extremities due to gravity effects. if the edematous tissue is compressed by pushing in with a finger, the compressed subcutaneous tissue will rebound slowly. This phenomenon is why this type of edema is called pitting edema.

INFLAMMATORY EDEMA.   This is also referred to as increased capillary permeability edema.  The fluid leaks from the vessel into the interstitial spaces because the inflammatory process causes the release of chemicals to affect membrane permeability. The inflammation also causes dilation of the vessels which increase the blood flow rate, augmenting the leakage.  This can result for the toxins of a bacterial infection or burn wounds.

OBSTRUCTIVE EDEMA. This type of edema is generally associated with an obstruction of the lymphatic system. The lymphatic system is a drainage system that removes excess interstitial fluid and returns it to the vascular system. Any type of obstruction to these thin walled vessels will cause edema. Causes for lymphatic obstruction are [1] tumors, [2] fibrosis due to inflamma    tion or irradiation, [3] and surgical ablation. African parasites (Bancroft’s filaria caused by Wuchereria bancrofti) cause inflammation and mechanical obstruction of the lymphatic vessels in the legs, arms, and or scrotum; producing a massive lymphedema known as elephantiasis.

ONCOTIC EDEMA. This is the result of a decrease in plasma colloidal oncotic pressure. If hypoalbuminemia is present, this oncotic pressure is decreased allowing increased transfer of fluid into the interstitial spaces. Hypoalbuminemia may be caused by protein loss due to renal disease or decreased protein synthesis because of liver disease. This form of generalized edema is seen most often in loosely textured tissue, especially in the face around the eyes as puffiness. If the eyes are swollen, this is known as periorbital edema.

04   DISTINGUISH BETWEEN TRANSUDATES AND EXUDATES.

This is an alternative way to classify edematous fluid. Transudates are essentially an ultrafiltrate of blood, containing little protein, few cells, and a low specific gravity. This clear fluid may accumulate in the tissues because of [1] increased hydrostatic pressure within the lumen of the blood vessel, [2] obstruction of interstitial fluid drainage (lymph vessels), [3] decreased oncotic pressure about blood vessels, and [4] increased sodium retention causing over-hydration of the tissues. No clots are expected to be observed in this type of fluid. Exudates are the consequences of inflammation. This fluid is increased in cells, protein, and specific gravity. It also may be cloudy in appearance. Clotting may be observed in this type of fluid. Any disorder that causes inflammatory responses will likely result in the formation of exudates.

TABLE: TRANSUDATES VS EXUDATES
        Description                        Transudates        Exudates
        Appearance                                   Clear                   Cloudy
        Specific Gravity                          <1.015                  >1.015
        Total Protein                               <3.0 gm/dL         >3.0 gm/dL  
        Fluid/Serum Protein ratio      <0.5                      >0.5
        Lactate Dehydrogenase           <200 IU/L          >200 IU/L
        Fluid/Serum LD Ratio             <0.6                      >0.6
        Cell count                                     <1000/μL            >1000/μL
        Spontaneous Clotting                       No                       Possible
        Pleural Fluid Cholesterol           <55 mg/dL           >55 mg/dL

  Best indicators for differentiation between the two type of edematous fluids.

05     ILLUSTRATE A SIMPLE MECHANISM FOR EDEMA.

       This figure illustrates the edema as caused by increased capillary porosity (permeability).  Other pathogenic factors that cause edema are (1) increased venous pressure resulting in an elevated capillary pressure, (2) low blood protein (hypoalbuminemia), or (3) obstruction in the lymphatic vessels.

06   EXPLAIN WHY EDEMA IS A CLINICALLY IMPORTANT SYMPTOM.

Edema may be an indicator of a dysfunction of a major organ and its location in the body may be a clue as to what organ is involved.  If the kidney is the cause of the edema, the edema will be diffuse, not focusing in a particular organ. In heart failure, the lower appendages will be involved. If the patient is “bedfast”, the edema will be obvious in the back. If the liver is involved, then ascites (due to abdominal accumulation of fluid) occurs.  Edema can be life threatening if it is confined to the brain.  Increased accumulation increases intracranial pressures which will depress the vital centers of the brain, causing death.  If the lung are filling with fluid because of left ventricular failure, then the patient will experience shortness of breath.  If the edema is located in the appendages, it may interfer with the collection of blood specimens.  It can affect laboratory values through a decreased hematocrit, lower sodium values, and low urine specific gravity.

07    EXPLAIN DEHYDRATION AS A FLUID DEFICIT.

Dehydration implies a deficient in body fluid due to a loss of water from the body or an inadequate intake of water into the body.  Losses usually occur first from the extracellular compartment.  The following is a generalized extracellular fluid loss
guide:
    A.    Decrease of 2% body weight is mild dehydration.   
    B.    Decrease of 5% body weight is moderate dehydration.
    C.    Decrease of 8% body weight is severe dehydration.

Dehydration impacts more severely upon infants and the elderly.  If dehydration is occurring, there is usually a loss of electrolytes and sometimes proteins.    Causes of dehydration are:
    A.    Vomiting and/or diarrhea  (with loss of water, electrolytes and glucose).
    B.    Excessive sweating (with increased loss of water and sodium).
    C.    Diabetic ketosis with dyuresis, glucosuria, and electrolyte loss.
    D.    Insufficient water intake (especially in an unconscious or elderly person).

Laboratory testing is affected with increases in lab values, including  the hematocrit and decreased urine volume causing a higher specific gravity.

08   DESCRIBE HEMORRHAGE.

Hemorrhage is a discharge of blood from its vascular compartment into a body cavity or to the outside of the body. The most common cause of hemorrhage is trauma. Two other causes of hemorrhage are aneurysms and certain bacterial infections.

An aneurysm is an abnormal dilation of a blood vessel wall due to a congenital defect or weakness.

If a patient is diagnosed with tuberculosis and left untreated, this bacterium can erode the walls of a blood vessel, causing lesions which bleeds into the into the lungs and the blood will be spit up (hemoptysis). Invasive tumors can invade any part of the body causing lesions, producing bleeding.

Hemorrhaging can occur at any level of the vascular system, from the capillary to the aorta. If a hemorrhage occurs internally, the loss of blood may be referred to as exsanguination.

09   LIST FOUR MAJOR TYPES OF HEMORRHAGES OR BLOOD LOSS.

[1] AORTIC HEMORRHAGE. This is often caused by trauma. The aortic wall is weakened and if the damage is significant, a massive hemorrhage occurs following quickly by death.
[2] ARTERIAL HEMORRHAGE. These are usually the result of trauma (knife wound, bullet, fracture of a bone). These hemorrhages are characterized by the pulsing of blood and the bright red color due to oxyhemoglobin. Unless stopped, these hemorrhages may be fatal.
[3] CAPILLARY HEMORRHAGE. Such hemorrhages are characterized by red pinpoint appearances of blood (petechiae) at the surface of the skin. This hemorrhagic occurrence may be due to trauma, vitamin C deficiency, weakened capillary walls, altered platelet integrity, or increased venous pressure.
[4] VENOUS HEMORRHAGE. This type of bleeding is non-pulsating and because the blood is deoxygenated, it tend to be a dark-reddish color. Causes for these type of hemorrhages are usually traumatic.

10   LIST ADDITIONAL TYPES OF HEMORRHAGE.

Note the following terms describes varying type of hemorrhage and may be arterial, capillary, or venous types of hemorrhage.

ECCHYMOSIS.  A large irregular formed hemorrhagic area just under the skin. The color will initially be bluish changing to a greenish and then to a yellowish color. Example: black eye.
HEMARTHROSIS. Hemorrhaging into a joint cavity.
HEMATEMESIS.  Hemorrhaging into the esophagus, stomach or duodenum with vomiting.
HEMATOCHEZIA.  Hemorrhaging from the anorectal area.
HEMATOMA.  Also intramural hematoma. A localized mass of extravasated blood confined to a space.  This may be considered as a type of hemorrhage.
HEMOPERICARDIUM.  Hemorrhaging into the pericardial cavity.
HEMOPERITONEUM.  Hemorrhaging into the peritoneal cavity.
HEMOPTYSIS.  Hemorrhaging into the lungs followed by spitting.
HEMOTHORAX.  Hemorrhaging into the pleural cavity.
METRORRHAGIA.  Hemorrhaging from the vagina. This is not menstrual bleeding. If the patient is experiencing extreme menstrual flow, it is called menorrhagia.
MELENA.  Hemorrhaging into the stomach or small intestine with subsequent action of digestive enzymes causing the fecal material to have a black, tarry-like appearance. This condition is most often seen in the newborn.
PETECHIA.  Pinpoint hemorrhaging capillaries and/or arterioles under the surface of the skin or the sclera of the eyes. Petechia are seen in bacterial endocarditis, coagulopathy, vasculitis, thrombocytopenia, and vitamin C deficiency.
PURPURA.  Small diffuse hemorrhages occurring just under skin, mucosal membranes or organ surfaces. The area of hemorrhage will be one centimeter or less. (In terms of size, this hemorrhagic area falls between petechiae and ecchymosis.)

11    BRIEFLY DISCUSS THE CLINICAL SIGNIFICANCE OF HEMORRHAGES.

The degree of blood loss through a hemorrhage determines the degree of risk. A younger person can tolerate hemorrhaging better than an older person. A single hemorrhagic incident has fewer consequences than a hemorrhage that repeats itself. The average adult can tolerate a loss of 500 mL with little ill effect (the amount drawn when donating a “pint” of blood to the Red Cross). If the blood loss in between 1000 and 1500 mL, then the patient is at risk of significant circulatory shock. If hemorrhage is greater than 1500 mL, then death is a real possibility. If the hemorrhage is small and periodic (chronic hemorrhaging), the patient usually presents with anemia. Normal menstrual flow is around 70 mL monthly. If the body had adequate nutrition, there are no health consequences other than inconvenience. If the body is not replenishing the lost hemoglobin and iron, anemia will result.

12   DISCUSS HYPEREMIA.

Hyperemia simply means that there is an excess of blood being supplied to the skin or other organs of the body. Hyperemia may be active or passive.

ACTIVE HYPEREMIA.  This occurs when the arterioles dilate and latent capillaries open up. This is observed during exercise, a situation that results in blushing, or because of an inflammatory response. During inflammation, vasoactive chemicals are released that cause dilation of the vessels followed by tumor (swelling), rubor (redness), and calor (heat). [(Note: another feature of inflammation may be dolor (pain).] For example, in pneumonia, the alveolar capillaries will dilate, then be packed with RBC’s. This is a hyperemic condition.

PASSIVE HYPEREMIA.  This is a phenomenon that occurs when venous pressure increases and the veins fill with blood. Such congestion is usually associated with a failure in the left ventricle. If the left ventricle is not contracting normally, blood cannot move into the atria. This results in the pulmonary vessels becoming engorged, causing the formation of a transudate in the alveolar sacs and a secondary diagnosis of pulmonary edema. The blood volume tends to increase in other body organs. The pulmonary edema is also characterized by extravasation of red cells into the alveoli where they disintegrate. The disintegrated cells are phagocytized by the alveolar macrophages (called dust cells). Ingested hemoglobin is degraded to hemosiderin and accumulates in the lysosomes of the macrophages. The macrophages are now called “heart failure cells”. Another consequence that occurs is hypoxia which influences the formation of fibrotic material. This fibrosis, with the presence of iron (from hemoglobin) causes brown lung. In passive hyperemia, other organs most often affected are the liver and spleen.

13   DISCUSS THROMBOSIS.

Thrombosis describes a process in which a clot of blood is formed that contains platelets, fibrin, and other cellular elements within a fibrin network. The formed clot is called a thrombus or hemostatic plug. A thrombosis may occur anywhere in the vascular system and in any organ. Thrombi (singular form is thrombus) are classified according to their location.

[1]    Arterial thrombi are found attached to the arterial wall.
[2]   Intramural thrombi are found within the heart chambers attached to the endothelium, usually overlying an area of myocardial infarction. Synonyms: mural, lateral or parietal thrombi.
[3]   Microvascular thrombi are located in the smaller vessels (arterioles, capillaries, and venules). These are small, strand-like “clots” and usually seen in disseminated intravascular clotting (DIC) disorders.
[4]   Valvular thrombi (may also be referred to as vegetations) are small and fibrinous abnormal growth-like protuberances that extended from the surface of the valve. The lesions that result mimic endocarditis. The lesions formed are designated as nonbacterial-type endocarditis.
[5]   Venous thrombi generally form in dilated or varicose veins. If these thrombi are present over a period of time, cells may invade the thrombus, causing changes and mimicking inflammation.

14    DISCUSS THREE PATHOLOGY FACTORS FAVORING ARTERIAL THROMBI FORMATION.

The most common cause is atherosclerosis, but is also caused by aneurysms, arteritis, trauma, and blood diseases. The most critical vessels in which thrombi occur and are life threatening are the cerebral, coronary, mesenteric, and renal arteries. One other group of arteries are those in the lower extremities. For blood clot formation in an artery, three things will take place:
[1]   the epithelium has been damaged (atherosclerotic plaque), causing the
         damaged area to serve a nidus or focal point for clot formation.
[2]   blood flow will be altered. Blood flow is slowed down favoring the forming of the
         clot.
[3]   the coagulability of the blood increases causing a tendency to easily form more
         clots.

15   DESCRIBE FOUR POSSIBLE OUTCOMES OF AN ARTERIAL THROMBUS.

When the thrombus is initially formed on the wall of the artery, it is soft, friable, and dark red. It will be characterized with fine alternating bands of yellow colored platelets and fibrin (called the lines of Zahn which help stabilize the clot). Four possible outcomes of this thrombus are:
[1]   The thrombus may undergo lysis. The blood has a number of enzymes that have
         powerful thrombolytic activity and can dissolve the clot.
[2]   The thrombus may increase in size serving as a foundation for additional
          thrombosis.
[3]   The thrombus may stimulate development of inflammatory cells (connective
          tissue cells) along with invasive vessels. The newly formed tissue is more firmly
          anchored and takes on a grayish-white color. This has been called the
          organization stage. The clot is slowly dissolved as the connective tissue takes
          over.
[4]    New channels may be formed (called canalization) through the clot and lined
          with endothelial cells re-establishing blood flow through that part of the vessel.

If the clot does not re-organize in one of the four identified outcomes and remain firmly attached, it may break away and form an embolus. The embolus may recirculate to another area and cause an infarct/infarction.

16    DEFINE AN INFARCTION AND LIST SEVERAL TYPES OF INFARCTIONS.

An infarct is an area of necrosis that results from a diminished or loss of blood flow and supply. Type of infarctions includes:
[1]   Embolic: due to a blood clot blocking blood flow to a tissue.
[2]   Septic: due to clumps of bacteria or infectious material blocking blood flow or
        it may be an infarction that has become infected.
[3]   Bone: an area of the bone that has become necrotic because of loss of blood
         supply.
[4]   Myocardial: results from the formation of a thrombus in one of the coronary
         arterial vessels and deprives that area of myocardium of it blood supply.
[5]  Cerebral: an area of the brain that becomes necrotic because of loss of blood
         supply.
[6]   Pulmonary: an area of the lungs that usually results from a pulmonary embolism.

17   LIST FIVE FACTORS THAT FAVOR THE FORMATION OF DEEP VENOUS THROMBI.

[1]    Stasis of blood flow. This includes such conditions as extended bed rest, post-
         operative immobilization, heart failure, and chronic venous insufficiency.
[2]    Injury. Any form of trauma, surgery, or childbirth.
[3]    Advance age.
[4]    Sickle cell disease.
[5]    Hypercoagulability.  (cancer, late pregnancy, or oral contraceptives)

18   DESCRIBE POSSIBLE OUTCOMES OF A VENOUS THROMBUS.

Up to 90% of venous thrombi occur in the deep vein of the legs, usually beginning in the veins of the lower leg (calf). The pelvic area of the body is a likely site for thrombi. Possible outcomes are the same as for arterial thrombi.
[1]    It is thought that most venous thrombi undergo lysis.
[2]    a venous clot can easily increase in size because it serves as a nucleus (or
        nidus) for additional clot formation.
[3]    If the venous thrombus is small, the clot may be organized into the wall of the
        vessel. If it is large, it may undergo canalization.
[4]    It is possible for a large thrombus to break away and be carried to the lungs
        and lodged there to form a potential risk for the patient.

If a thrombus forms near or on a venous valve, it will likely impair the function of that valve, causing additional problems for the patient.

19    DISCUSS FOUR PATHOLOGIES IN WHICH THROMBI MAY FORM IN THE HEART.

Thrombi can form in the heart as in arteries or veins. The conditions which favor the formation of mural thrombi are:
[1]    Atrial fibrillation. This disorder allows for the slowing down of the blood flow. Though this is not true stasis, in some patients, the reduced blood flow favors thrombus formation.
[2]    Cardiomyopathy. This is any primary disease of the heart. It is thought that there is some degree of myocardial injury on the myocardial wall along with modified hemodynamics in blood flow and changes in the contractility of that region. Thrombi formation become favorable.
[3]    Endocarditis. Bacterial infection that localizes on the heart valves causes small lesions. The lesions in turn forms the nidus that allows for small thrombi to form. These thrombi are called vegetations.
[4]    Myocardial infarction. In a heart attack, the myocardium is damaged which results in a loss of dynamics in blood flow. The lesion provides an attachment site for the clot to form.

20    DESCRIBE AN EMBOLUS AND LIST SEVERAL FORMS AND PROVIDE A BRIEF DESCRIPTION FOR EACH ONE LISTED.

An embolus is an intravascular mass that can move freely through the arterial or venous vessels. It has the potential to lodge in a blood vessel and obstruct the lumen. Most emboli are blood clots (designated as thromboemboli [plural] or thromboembolus [singular]). Remember that the blood clot will form at one site and one of its four options is to detach and move to a distant site. The following represents the four basic forms of emboli:.
                                               GASEOUS EMBOLI.  
This is an air emboli that can be introduce by the direct injection of air, neck wounds, thoracocentesis, puncturing the great veins during an invasive procedure, or hemodialysis. Note that those who work in modified atmospheres (scuba divers and other underwater occupations), upon returning to the normal atmospheres must do so at a rate that allows for the air in the body to equilibrate with the outside. Failure to do so causes caisson disease or compression sickness, which are forms of air embolism. Most gaseous emboli are small and are rapidly dissipated. If 100 mLs of air (or more) is introduced into the vascular system, sudden death can result. Air bubbles tend to coalesce and can physically obstruct blood flow in critical areas of the brain, heart, and lungs.   Underwater workers will work in an inert gas environment of helium or nitrogen. When they ascend slowly, the gas is released from the body fluids at a rate that can be easily exhaled. If the ascent takes place too quickly, then gas bubbles will form and coalesce, obstructing blood flow, causing cell injury and even death.
                                                LIQUID EMBOLI
A.    Amniotic fluid . . . occurring at childbirth when the fluid enters into the uterine
        veins during delivery.
B.     Fat . . . is released into the damaged vascular system following some form of
         trauma. If the fat embolism is small, there are no consequences. If it is large,
         then symptoms will show up in 24 to 72 hours. The potential to be fatal is a
         real risk. Symptoms include mental changes, respiratory changes,
         thrombocytopenia, and petechiae over the body.
                                    SOLID PARTICLE EMBOLI
A.     bone marrow . . . is found to most often occur those patients who underwent a
         cardiac resuscitation procedure, with the bones of the sternum and ribs being
         fractured. The emboli consists of fat and hemopoietic cells. Such emboli are
         asymptomatic and are found during autopsy.
B.     cholesterol crystals . . .  have been reported. These crystals become detached
         from atheromatous plaques and block microcirculation.
C.     tumor cells . . .  will be released from a tumor site and migrate to a distant site
         and attach. Since tumor cells can be invasive and reproduce themselves they
         will occlude the vascular system and infect the surround tissues/organs.  This
          type of movement is known as metastasis.
                                                  THROMBOEMBOLI
These arise from the deep veins of the lower extremities or the heart. They are of two types, venous and arterial. Venous emboli typically lodge in the arteries of the lungs to cause pulmonary embolism. Arterial emboli are released from the walls of the heart, heart valves, or aneurysms. Such emboli will undergo fragmentation and lodge in the medium and small arteries  of various organs. The greatest risk associated with arterial emboli are those that lodge in cerebral circulation and cause strokes. Other organs commonly affected are the:
A.    Intestines.    An embolus that blocks a mesenteric artery causes acute
        abdominal pain and quick medical intervention is recommended.  Infarction or
        gangrene are real risks, especially in the older adult.
B.     Kidneys.    There is a potential for renal artery occlusion that affect the entire
         kidney, but in most incidents, small peripheral infarcts are the rule.
C.    Lower extremity.    If an emboli occurs that blocks a major artery, there will be
        sudden pain, the limb will turn cold, and a pulse will be absent. If the limb does
        not recover, amputation may be the only alternative.
D.    Spleen.    Splenic emboli are often functionally unimportant and the only
        problem a patient may sense is a sharp, subcostal pain.

21   BRIEFLY DISCUSS THE CLINICAL AND PATHOLOGICAL SIGNIFICANCE OF EMBOLI.

Emboli are significant in that they can occlude blood vessels and impede circulation. Thromboemboli are the most common forms found in clinical practice. The other types (gas, fat, and solid particle) are of rare occurrence. It is estimated (hospital statistics) that 50,000 people die annually from pulmonary emboli. This does not include those that die outside the hospital and are not detected. Pulmonary emboli are asymptomatic or display non-specific symptoms in up to 40% of the cases and are discovered during autopsy. Pulmonary emboli tend to affect the older generation, those confided to prolonged bed rest, or suffering from some chronic disease. Arterial emboli pose the greatest risk in cerebral circulation causing strokes.

22    DESCRIBE A PARADOXICAL EMBOLISM.

This embolus is formed in venous circulation and avoids the lungs and will lodge in somewhere in the arterial system. This occurs when there is a opening in the septum of the heart (a partially closed foramen ovale) which permits the clot to pass from the right side of the heart to the left side and enter arterial circulation.

23    DEFINE A SADDLE EMBOLUS.

This is a very large embolus that can occlude the pulmonary artery or its main branches. The term saddle may come from the appearance of the clot as it occludes the branching pulmonary artery at it bifurcation. This type of embolus is often lethal.

24   DEFINE AN INFARCT.

Rudolf Virchow (German pathologist, 1821 - 1902) took the ancient term “infarct” and used it to describe an area of necrosis due to an embolus. An infarct is the result of the total occlusion of an artery, shutting off the blood supply to a tissue area, resulting in death and necrosis of that tissue. The term “infarct” implies an anatomic lesion and the term “infarction” is the process that leads to the lesion. Both terms tend to be used synonymously.   Note that infarcts can also occur in veins.

25     DISCUSS THE CLINICOPATHOLOGY OF AN INFARCT.

The appearance of an infarct depends on it age and location. When a clot occludes a vessel, the area supplied by that vessel will first become swollen and take on a dark red appearance because of the vascular dilations and congestion. There may be some interstitial hemorrhage. With this beginning, the infarction will progress into either a white (pale) or red infarct.

The pale or white infarct generally occurs in solid tissue organs like the brain, kidney, heart, or spleen from an occluded artery. These areas usually do not regenerate. The area of occluded circulation will take on a pale appearance with the presence of a reddish rim at the periphery of the infarct. This reddish ring of peripheral color is due the hemorrhaging into the surrounding viable tissue.

The red infarct is the result of either arterial or venous occlusion. These tend to occur in those organs with dual circulation (liver, lungs, small intestine, or testis). It is possible for these areas to regenerate. Red infarcts tend to be sharply delineated with dark red to purple color, and have a firm texture. Over the next several days, the tissue will undergo necrosis and inflammatory cells will invade the area. Granulation tissue will first develop and is then replaced by scar tissue. If this type of infarct should occur in the brain, the tissue will undergo a liquefying type of necrosis and eventually form a fluid-filled cyst. Red infarcts can form in the intestines when the organ twists around some supporting structure (a phenomenon known as volvulus), which results in compression of the veins (their walls are thinner and more easily compressed that arteries) of the mesentery. Venous congestion results, followed by local ischemia, and then necrosis.

If the infarcted tissue contains facultative mitotic cells (as does the liver) then the infarct will heal with little harmful effects. There is a limit to how effective infarcted tissue can repair itself. If the infarct is large, there will likely be defects in the tissue and scar tissue will present. Heart muscle does not have these pre-mitotic cells and cannot repair itself except by replacing the damaged cells with scar tissue. This is true for the brain.

There are septic infarcts. These occur when an infarct becomes infected by pyogenic bacteria. Inflammation will set in and the infarcted area will form into an abscess. It is not unusual for a pulmonary infarct to become infected because of its location in the body and infarcted tissue has little resistance to invasive bacteria.

26   DISCUSS THE MYOCARDIAL INFARCTION.

The coronary vessels become occluded and myocardial necrosis sets in. In many cases, the underlying cause is atherosclerosis, with or without a thrombus. This type of infarct will be typically characterized by severe chest pain, lasting from 30 minutes and up to several hours. The temperature will elevate, usually between 24 to 48 hours and return to normal in about seven days. The patient may experience any combination of dyspnea, pallor, restlessness, sweating, nausea, and vomiting symptoms. The blood pressure will be variable, but bradycardia and hypotension are not uncommon. The patient may describe their extremities as being cold. Some patients will be terrified and fearful of impending doom.

Consequences that follow the onset of the infarct may include ventricular tachycardia or fibrillation. The loss of blood flow to that area of the heart (ischemia) may cause faulty conduction through the AV node (known as heart block). When this occurs the ventricles may contract independently. Decreased cardiac output may result. If the heart is failing to efficiently pump blood, then the inadequate volume of blood may result in cardiogenic shock, inducing circulatory failure. Death is a real risk.

Complications of a myocardial infarction include:
[1]    myocardial rupture when the necrotic myocardium become soft and cannot resist the increased hydrostatic pressure within the ventricle. If the rupture is large, then it is fatal. a small rupture may allow bleeding into the pericardium.   If sufficient bleeding occurs into the pericardial cavity, the heart is compressed, a condition known as cardiac tamponade. This condition usually sets up in five to seven days following the infarction. It can be lethal.
[2]    cardiac aneurysm occur after an significant heart attack involving the left ventricle and the patient has recovered. The infarcted area has been replaced by scar tissue. These scarred area will bulge because of the lack of contractile tissue. Over time, the heart will dilate and begin to contract irregularly.
[3]    formation of a mural thrombus because the myocardium is damaged by the infarct causing disruption of the endocardium. The damaged and necrotic area can serve as a nidus for clot formation. The thrombus will be attached to the wall of the heart. See Objective # 14 regarding the fate of a thrombus.

27    DISCUSS CONGESTIVE HEART FAILURE.

This disorder of the heart is due to the increased volume of the venous side of pulmonary and/or systemic circulation. The blood is being backed up behind both ventricles. There is an impaired contractility of the myocardial tissue which results in low cardiac output leading to low systolic pressures. These low arterial hydrostatic pressures translates into a stagnant venous blood pool characterized by impeded blood flow to the heart.

If the right ventricle is failing, cannot maintain its output with less blood being pumped to the lungs and back to the left ventricle. There will be a congestion of the peripheral regions, with the legs becoming swollen. There is increased resistance in the peripheral blood vessels. The liver enlarges and the formation of ascites is likely due to hypertension in the abdominal veins.. Pulmonary circulation is affected, resulting in an increased blood volume and congestion in the lungs, which adversely affects the heart and body. Causes of right ventricular failure include:
        [1]    pulmonary stenosis,
        [2]    pulmonary hypertension,
        [3]    atrial septal defects.

Cor pulmonale refers to right-sided congestive heart failure and usually results from pulmonary disease.

If the left ventricle is failing, there will be passive pulmonary congestion and pulmonary edema. The cause of often due to increased peripheral resistance which causes hypertension. The ventricle will eventually become unable to maintain it stroke volume and cardiac output. The blood tends to back up in the left atrium, which in turn causes congestion of the pulmonary vascular system. Causes of left ventricular failure include:
     [1]    hypertension due to peripheral resistance,
     [2]    aortic stenosis,
     [3]    coarctation (constriction or compression) of the aorta,
     [4]    mitral regurgitation.

The right and left ventricles are continuous pumping systems and do not operate independently of each other. If one ventricle is adversely affected, it will have a negative impact upon the other ventricle.

28    DISCUSS SHOCK.

Shock is a condition of circulatory collapse in which there is a significant hemodynamic and metabolic disturbance takes place, resulting in hypoperfusion of blood in the vital organs. Shock can result from [1] a loss of fluid from circulation, [2] the failure of the heart to pump blood, or [3] a change in peripheral vascular tone that allows redistribution of blood and fluids away from vital organs. Regardless of the cause, there will be a collapse of circulation, plus a disproportionate distribution of circulating fluids between tissues. This sudden hypoperfusion of tissues results in hypoxia and will lead to organ failure. Decreased perfusion of the tissues results in metabolic acidosis which depresses cardiac output. Tissue cells are injured and they release metabolic chemicals which increases vascular permeability, facilitating fluid redistribution. The hypoxia will lead to anoxia and augments continued loss of vascular tone. The end stage of shock is cardiopulmonary collapse and death.

29    DESCRIBE HYPOVOLEMIC SHOCK.

Hypovolemic shock occurs when there is a loss of intravascular volume with a corresponding decrease in blood flow. This is the most common form of shock. It may result from hemorrhage due to trauma or a disease process that causes internal bleeding. Excessive fluid losses may occur with diarrhea, perspiration, urination, or vomiting. Extensive burns with fluid loss can contribute to this type of shock. Anaphylaxis, an acute allergic reaction can affect the microcirculation causing loss of intravascular circulation to the interstitial compartment and circulatory failure. The pronounced decrease in blood volume will result in a reduced venous return to the heart and decrease the cardiac output. When the blood volume decreases by 25%, both cardiac output and systolic pressure decreases. There will be a increase in the activity of the sympathetic nervous system producing tachycardia, hyperventilation, and peripheral vasoconstriction. Renal blood flow decreases causing oliguria. Cerebral blood flow diminishes and the symptoms of confusion and apprehension appear.

30    DESCRIBE CARDIOGENIC SHOCK.

Cardiogenic shock occurs when the heart does not contract efficiently to pump blood. This condition sets in when there is a myocardial infarction, myocarditis, or pericardial tamponade. These disorders causes decreased contractility, abnormal rate, and/or abnormal rhythm. Systolic pressure will drop below 90 mm Hg, the skin will become cold and clammy with cyanosis. There is reduced mental awareness and oliguria.

31   DESCRIBE DISTRIBUTIVE SHOCK.

Distributive shock occurs when there is [1] obstruction to blood flow, [2] alteration in cardiac function, and [3] changes in the blood volume. One dysfunction that contribute to this type of shock is the dilation of the venous vessels which results in a reduction of venous return and causes a decrease in the cardiac output. Another dysfunction is the vasodilation of the arterioles, which causes changes in peripheral resistance. The blood may be shunted from the capillary beds by the metarterioles. This shunting phenomenon is arteriovenous shunting.

Other causes of distributive shock may be induced by septicemia, spinal cord transection, or overdosing with narcotics, barbiturates, or tranquilizers. Consider the events that following in a septicemia by gram-negative microorganisms.

A.     Note that about 25% of patients with a gram-negative septicemia will develop shock.
B.    In the initial stages, vasodilation of the arterioles occurs with the blood being shunted to the venues and the capillaries being bypassed. Note that there is not a total cessation of capillary perfusion. It will be inadequate.
C.     Bacterial cell wall products begin to activate compliment and neutrophils. There is also damage to the endothelial cell walls of capillaries and other tiny blood vessels which increase membrane permeability cause “leakiness”.
D.     Bacterial products activate clotting factors causing formation of small thrombi along with platelet aggregation. This leads to Disseminated Intravascular Coagulation (DIC) with the appearance of microthrombi in the capillaries.
E.    Bradykinin and endorphin are being synthesized and released which augment vasodilation and capillary permeability.
F.    If this occurs in pulmonary capillaries, pulmonary edema occurs, setting the patient up for respiratory failure.
G.    Blood pressure drops and there is a corresponding decrease in cardiac output.
H.   The body tries to compensate by increasing vasoconstriction and peripheral resistance.
I.    Cerebral blood flow begins to decrease, leading to mental confusion and disorientation.
J.    The inadequate perfusion of the kidney and visceral organs may lead to oliguria, vomiting, and diarrhea; complicating the problem.
K.    Inadequate perfusion of body tissues will cause metabolic acidosis which impacts negatively upon cardiac output.

There are five treatment strategies that mayl be implemented to counteract this form of shock.   FIRST:  restore fluid volume with appropriate I.V. solution,   SECOND:  give a diuretic to prevent oliguria,   THIRD:  administer oxygen to raise the decreased pO2,   FOURTH:  administer bicarbonate to adjust pH, and FIFTH: administer glucocorticoids to counteract inflammation.

32    BRIEFLY DESCRIBE HOW SHOCK AFFECTS THE ADRENAL GLANDS, GASTRO-INTESTINAL TRACT, HEART, KIDNEY, LIVER, LUNG, AND PANCREAS.

[1]    ADRENAL GLANDS.  The adrenal glands, in severe shock will hemorrhage into the cortex. Hemorrhage may be minor, affecting a small area. If the hemorrhage is massive, it can cause necrosis of the entire gland.
[2]    GASTROINTESTINAL TRACT.  The GI tract usually experiences diffuse bleeding which affects the gastric mucosa, causing some erosion. There may be some superficial ischemic necrosis.
[3]  HEART.  The heart will demonstrate tiny hemorrhages in the epicardium and endocardium. Larger hemorrhage is possible and may result in necrosis.
[4]   KIDNEY.  Shock adversely affects the tubules of the nephron and result in tubular necrosis. The kidney may swell, becoming congested. Pigmented casts (containing hemoglobin and myoglobin) are formed.
[5]   LIVER.    The liver may become congested and demonstrate centrilobular hemorrhagic necrosis.
[6]   LUNG.   If shock is profound, alveolar wall injury may result. The victim may experience acute respiratory distress syndrome (ARDS).
    A.   These are changes that occur in the lungs and leads to acute
           respiratory failure.
    B.    Such changes can occur with injury to the endothelial cells of the capillary
           or alveolar lining cells.
            a.    Injury cam be implemented by viral pneumonia or intra-alveolar
                   exudate from bacteria and leukocytes in the alveoli.
            b.    Other injury causes are inhalation of hot air causing pulmonary burns or
                   breathing in of toxic fumes.
            c.    Cytotoxic medication can produce alveolar injury.
    C.     There is an increase in the permeability of the alveolar blood vessels with
             an accompanying fluid accumulation in the alveolar spaces.
    D.      Impaired oxygenation of the blood occurs and with anoxia.
    E.      Pulmonary circulation becomes impaired which leads to heart stress
             followed by heart failure and then death is it is not corrected.
    F.      ARDS is characterized by:
             a.    diffuse alveolar damage.
             b.    edema in the lungs.
    G.     ARDS symptoms include shortness of breath (example: gasping), hypoxemia,
             and hypercapnia.
    H.     ARDS patients are prone to infections and may have a poor prognosis.
    I.      Statistically, one-third die in days due to complications, one-third develop
             pneumonia and heart failure and die. Those who recover tend to have
             permanent residual respiratory problems.
    G.     If a patient is diagnosed with chronic respiratory distress, it may be
             resultant of shock.
[7]     PANCREAS. The pancreas has an extensive vascular bed, which is impaired
 .        during shock. Ischemic damage can release activated catalytic enzymes that
         causes acute pancreatitis and augments the shock phenomenon.

32    EXPLAIN THE TERM “COMPENSATED SHOCK”.

This is a stage of shock in which the body tries to counteract any circulatory imbalances. At least three things are observed in this stage.

[1]   TACHYCARDIA. The heart increases it stroke rate to pump more blood to the vital organs.
[2]    VASOCONSTRICTION OF THE PERIPHERAL ARTERIES. Constriction of these arteries shunts the blood from the skin and appendages, which causes pallor. The shunted blood perfuses the brain, heart, and other vital organs.
[3]    REDUCED URINE PRODUCTION. There is less blood flow through the glomeruli, decreasing the rate of urine production. The kidney releases renin to stimulate aldosterone and antidiuretic hormone production to enhance fluid retention.

An example of this stage may be observed in a person who had donated a “pint” of blood to the Red Cross. This represents about a 10% blood loss.

33    EXPLAIN THE TERM “DECOMPENSATED SHOCK”.

This is a second stage of shock, in which the first stage (compensated) has failed. a person entering into this stage may have lost from 15% to 25% of their blood volume. The following four conditions occur.

[1]    HYPOTENSION.  Blood pressure falls as the cardiac output falls as the body tries to redistribute larger volumes of blood to the brain, heart, and other vital organs. There is a generalized venoconstriction occurring. Fluid will move from the interstitial compartment to the vasculature which will decrease the hematocrit.
[2]     TACHYPNEA.  This will cause a compensatory respiratory alkalosis. Reduction in the number of oxygen transporting RBC’s causes air hunger and shortness of breath. If compensation does not occur the patient will develop Adult Respiratory Distress Syndrome (ARDS).
[3]     OLIGURIA.  Vasoconstriction of the afferent arterioles reduces glomerular filtration and restricts renal fluid output.
[4]     ACIDOSIS. This pH imbalance occurs due to metabolic disturbances and tissue anoxia (favoring anaerobic glycolysis that increases lactate production and CO2 retention).

Other symptoms are: pallor, cold distal extremities, diaphoresis, piloerection, apprehension, and restlessness.

34    EXPLAIN THE TERM “IRREVERSIBLE SHOCK”.

This is the end state of decompensated shock and leads to death. If the patient cannot fully mobilize the compensatory mechanisms and/or there is additional blood loss, there will be a rapid deterioration of circulation (loss of cardiac output, increased drop in blood pressure, and additional loss of tissue perfusion). Venous return is reduced and ceases. Cellular injury will become more wide spread and severe ischemia to the vital organs ensues. Organ function is impaired and will cease. Potassium ions, vasoactive compounds, intracellular lysosomal enzymes, and peptides are released from the cells into circulation. Capillary permeability is compromised and cellular fluid, proteins, and other constituents seep into the blood. Platelet aggregation is exacerbated and disseminated intravascular coagulation (DIC) takes place. ARDS develops. Oxygen-derived free radicals are formed and released causing post-ischemic tissue injury. Once in this phase, mortality is very high.

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This page last updated 07/28/08