Topic: Alterations of Hematology and Cardiovascular Systems - Case Study 1 & 2

NRS-410V Lecture 3

Alterations of Hematology and Cardiovascular Systems

Introduction

Blood is the river of life. Blood transports nutrients and oxygen to all the organs and tissues and also carries away tissue waste and debris. Chemical messengers, clotting factors, anticoagulant factors, cells that fight bacteria, and numerous other components are carried by the blood. To be effective, the blood must stay liquid, but not too liquid, and it must be pumped through the circulation system to all tissues. Alterations in the red blood cell, the clotting components, the blood vessels, and the ability of the heart affect the entire system.

The Erythrocyte

The erythrocyte, or red blood cell (RBC), is the most numerous component of the blood. The function of the RBC is to transport oxygen to the tissues and also carry carbon dioxide back to the lungs. A complete blood count (CBC) is essential in evaluating the status of the hematopoietic system. The RBC count that is decreased may indicate an anemia. A reticulocyte count, which is more or less than 1% of the RBC count, helps determine if the cause of the anemia is due to blood loss, increased RBC destruction, or the bone marrow not functioning. An increase in reticulocytes may be seen with some anemias as the body tries to compensate.

Anemia

Anemia is a broad term used to indicate that there is a decreased oxygen-carrying capability of the blood. The lack of RBCs may be the result of an abnormally low production of red blood cells due to marrow failure, actual loss of RBCs due to bleeding, decreased erythropoietin secretion by the kidneys, or nutritional deficiencies. The effect of the decreased oxygen is tissue hypoxia that causes an increase in heart rate and respiratory rate as a compensatory response. Other symptoms include pallor, headache, light-headedness, and night cramps in the muscles. The RBC indices of MCH, MCV, MHCH, and RDW help identify the cause of the anemia (Porth, 2007).

Iron Deficiency Anemia

Iron deficiency anemia is the most common type of anemia worldwide. A dietary deficiency of iron is often the cause, but chronic blood loss has also been implicated. The RBCs are microcytic and hypochromic. They may also exhibit an irregular shape (poikilocytosis). The signs and symptoms with this anemia will include pallor, fatigue, palpitations, dyspnea, tachycardia, and sores in the corners of the mouth. The treatment for this condition is supplemental iron.

Vitamin B12 Deficiency

Vitamin B12 (cobalamin) deficiency is linked to a decreased secretion of intrinsic factor by the parietal cells of the stomach, or the inability of vitamin B12 to be absorbed from the ileum. Vitamin B12 is vital to the synthesis of DNA in rapidly proliferating cells such as the red blood cells. Without the appropriate amount of vitamin B12, the red blood cells become hyperchromic, or oval-shaped with a flimsy membrane, and their lifespan is only several weeks. Vitamin B12 also protects neurons from demyelination, which has been linked to abnormal fatty acids becoming part of the myelin. It is the demyelination that causes bilateral paresthesias of the feet and hands and loss of proprioception. Cerebral signs include irritability; perversion of taste, smell, and vision; paranoid ideation, cognitive dysfunction, and dementia. The treatment for this deficiency is intramuscular injections of vitamin B12, unless it is strictly a dietary deficiency, in which case, increasing intake of meat and dairy products is the solution. Individuals who have had gastric bypass surgeries usually require supplemental B12.

Folic Acid Deficiency

Folic acid deficiency is a dietary deficiency often associated with chronic alcoholics and the elderly. In addition, pregnancy increases the need for folic acid by 10-fold, and between poor eating habits, nausea, and vomiting, there can also be a folic acid deficiency (Porth, 2007). Phenytoin to treat seizures and methotrexate to treat cancer and arthritis may block the absorption of folic acid, causing a deficiency (Porth, 2007). Folic acid is found in vegetables, fruits, cereals, and meats, but is inactivated with cooking. The result of folic acid deficiency is that RBCs become larger than normal, have a short lifespan, and have a flimsy membrane. The signs and symptoms are related to decreased oxygen with no neurological component.

Inherited Anemias

Sickle Cell Disease

Sickle cell disease is an autosomal recessive disease that alters the hemoglobin such that the RBCs tend to sickle in response to decreased oxygen, occluding small capillaries anywhere in the circulation causing local tissue ischemia and pain. A sickling crisis can be brought on by a cold, stress, physical exertion, infection, hypoxia, dehydration, or acidosis. Although bone marrow or stem cell transplant is the only known cure, the risks are great. In the majority of cases, treatment for this disease consists of hydration, supplemental oxygen, and pain control along with management of any complications secondary to vessel occlusions and organ damage.

Thalassemia

Thalassemia is also an inherited recessive disease in which either the α or β globulin chains are defective, causing a decrease in hemoglobin production. The unaltered globulin chains accumulate in the RBC and interfere with maturation. The anemia that results is hypochromic and microcytic. Similar to other anemias, the signs and symptoms are related to decreased oxygen to the tissues. A major complication specific to β-thalassemia is excess iron stored in the heart, liver, and endocrine organs, which causes organ damage. In some instances, transfusions and chelation therapy can improve the anemia and reduce the iron overload.

Clotting and Bleeding Disorders

As technology has advanced, hosts of clotting and bleeding disorders have been identified. Many of them are related specifically to one or two clotting factors that, because of genetics, are manufactured incorrectly and either work too well or not well enough. However, the greatest risk continues to be the development of clots. Embolic and thrombotic strokes, pulmonary emboli, and deep vein thrombosis are directly related to the formation of clots. Many of the drug therapies directly affect the clotting and anticoagulant factors.

There is a delicate balancing act between the clotting factors and the anticoagulation factors to maintain the liquid status of the blood. Sepsis, inflammation, decreased blood flow, and a variety of diseases contribute to an alteration in this balance. The clotting process is explained in the textbook. Below are several of the key components:

AT-III, a clotting factor in the blood, inactivates any accidental thrombin roaming around in the blood. Inflammation and sepsis decrease the available AT-III and increase the risk of clotting (McCance & Huether, 2006). AT-III replacement is available and is useful in treating DIC associated with sepsis (McCance & Huether, 2006).

Protein C and protein S are produced in the liver and require vitamin K. Together they are called thrombomodulin, which binds to thrombin and prevents thrombin from causing fibrinogen and platelets to clot (McCance & Huether, 2006). Inherited deficiencies of protein C and protein S dramatically increase the risk of clots. Inflammation and sepsis also decrease the activity of protein C and increase the risk of clotting.

Tissue factor pathway inhibitor (TFPI), also produced by endothelial cells, inhibits factor Xa, a major clotting factor. Heparin and low-molecular weight heparin are administered to augment the heparin produced by endothelial cells. Activated partial thromboplastin time (APTT) is used to measure the effectiveness of heparin in decreasing clotting.

Opposing the anticoagulation factors are the clotting factors. All of the clotting factors except von Willebrand factor are formed in the liver. Vitamin K is specifically needed for factors VII, IX, X, prothrombin, and protein C (Porth, 2007). Damaged endothelial cells release tissue factor (TF), the primary initiator of coagulation, which initiates the formation of a clot. Warfarin (Coumadin) blocks the insertion of Vitamin K in the clotting factors, rendering them ineffective and decreasing clotting. Although the pro time (PT) test is used to measure the effectiveness of Coumadin, the International Normalized Ratio (INR) has become the prevailing standard.

Platelets are integral to clot formation by producing several chemicals. COX-1 is inhibited by aspirin, thus decreasing the activation of thromboxane A (TXA2), which causes platelets to clump. Nitrous oxide (N2O) secreted by the endothelial cells also inhibits platelet aggregation.

Circulation

The heart propels the blood through a vast array of vessels, while the nervous and endocrine systems assist in maintaining the volume and strength of this blood flow. As the pump, the heart itself may be affected by pathological problems that alter its ability to pump effectively. In addition, the blood vessels themselves are affected by a variety of disorders. Hypertension and atherosclerosis increase peripheral vascular resistance, causing the pump to work harder and eventually causing left ventricular hypertrophy, which may lead to cardiac arrhythmias, congestive heart failure, and sudden death.

Hypertension

Hypertension is a complex disease. Genetics, environment, and lifestyle play key roles in the development of hypertension. Essential hypertension is due to alterations in one or several of the following processes that alter peripheral vascular resistance and blood volume:

Adducin is a protein found in the cellular membrane and is important to the regulation of the sodium-potassium pump. Mutations in the gene that codes for adducin increase the risk of hypertension in Caucasians (McCance & Huether, 2006).

Via the sympathetic nervous system, either increased catecholamines or increased receptor activity raise heart rate and blood vessel tone.

Dysfunction of the renin-angiotensin-aldosterone (RAA) system generally increases peripheral vessel resistance and retention of sodium by the kidneys. Antihypertensive medications such as angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers, and beta blockers decrease the effects of the sympathetic and RAA systems.

Insulin resistance is found in individuals without diabetes and contributes to endothelial dysfunction. Endothelial cells produce nitric oxide (N2O), which is a vasodilator. A decrease in production allows for constriction and an increase in platelet aggregation. Drugs that stimulate nitric oxide production and decrease insulin resistance are being researched as a way to decrease blood pressure.

Obesity, high salt intake, sedentary lifestyle, excessive alcohol, and sleep apnea have been identified as contributing to the development of hypertension (Porth, 2007).

Atherosclerosis

Atherosclerosis is a complex inflammatory process that begins with damage to the endothelial cells within arterial vessels. Hypertension, elevated low-density lipoprotein (LDL) levels, decreased high-density lipoprotein (HDL), smoking, diabetes, and other risk factors cause damage to the endothelium. Inflammatory cytokines, growth factors, and macrophages further injure the vessel wall. The process of developing plaque is described in the textbook. Elevated C-reactive protein (CRP) serum levels are considered an indication of increased risk for atherosclerosis (Porth, 2007).

A primary culprit in plaque is LDL, a carrier for cholesterol. Hypercholesterolemia may be genetically linked and/or linked to increased dietary intake of cholesterol. Diabetes predisposes individuals to increased cholesterol. The treatment is to eliminate or control the risk factors, decrease the risk of plaques rupturing, and maintain blood flow past the narrowing of the artery.

Heart

The function of the heart is to pump blood through the vessels, deliver nutrients and oxygen to the tissues, and pick up waste products. Considering the pathologies of the heart, one can view them from their effects on stroke volume: cardiac output, preload, afterload, contractility, and heart rate.

The sympathetic nervous system for cardiovascular control primarily in the medulla causes the release of norepinephrine, which stimulates the β-adrenergic receptors on the cardiac cells. β1 receptors increase heart and contraction, while β2 receptors in the coronary arterioles cause vasodilation. Beta blockers such as Toporol and atenolol block norepinephrine, thereby decreasing heart rate and strength of contraction. The parasympathetic nervous system dominates via the vagus nerve, releasing acetylcholine, which maintains or decreases the rate. Atropine, an anticholinergic, is used to block acetylcholine and increase the heart rate. Inflammation and cardiac cell damage secondary to myocardial ischemia or infarction potentially affect the relay of the impulse down the conduction system, causing arrhythmias.

Myocardial Ischemia/Infarction

Myocardial ischemia and/or infarction are most often caused by blockage of the coronary arteries secondary to plaque build-up. But anything that decreases blood supply to the myocardium or decreases oxygen to the myocardium will also cause cell damage. The extent of the damage can be reduced if perfusion to the area is reestablished within 15 to 20 minutes (Porth, 2007). Damaged cardiac cells release enzymes into the blood that can be measured (Porth, 2007). Necrotic tissue is replaced with scar tissue that does not function as normal cardiac cells do, leading to complications such as permanent arrhythmias, heart failure, and ventricular aneurysms.

Anatomy of Heart Failure

Heart failure commonly associated with myocardial infarctions may also be caused by valvular disease, pericarditis, and pulmonary disease. While many patients have what we call congestive heart failure, it identifies the symptoms rather than what areas of the heart are not functioning well. For example, a blocked left anterior descending coronary artery may cause extensive damage to the left ventricle. With the remodeling process, the ventricle loses its ability to stretch and contract, thereby decreasing the ejection fraction (normally 65% of what is in the left ventricle). As cardiac output decreases, renal perfusion decreases, causing the RAA system to be activated. Fluid is retained, increasing the preload, while the sympathetic system increases heart rate and causes vasoconstriction, increasing afterload. Instead of helping the heart, these protective mechanisms actually make it work harder. Fluid eventually backs up into the lungs, causing pulmonary edema, which further decreases oxygen to the myocardium.

Natriuretic peptides are produced in response to fluid overload in the atria and ventricles. The levels of B-type natriuretic peptide (BNP) are now being used to diagnose or rule out heart failure (Porth, 2007). Nesiritide is a recombinant form of human B-type natriuretic peptide currently being used to treat individuals with acute severe decompensated congestive heart failure (CHF) (McCance & Huether, 2006). Treatment of heart failure involves decreasing fluid volume, slowing the heart rate, increasing oxygen to the heart, and improving circulation.

Conclusion

Hypertension, coronary heart disease, heart failure, and anemia are common pathological conditions being treated every day. Assessment of these systems begins with basic history questions, vital signs, and a CBC. Laboratory tests can be used to further differentiate the cause and also evaluate the treatments. Diet, exercise, and environment are linked to the causes of these conditions, as well as being part of the cure. Thus, understanding how the systems function together and how the treatments work is important.

References

McCance, K. L., & Huether, S. E. (2006). Pathophysiology: The biological basis for disease in adults and children (5th ed.). St. Louis, MO: Mosby Elsevier.

Porth, C. M. (2007). Essentials of pathophysiology: Concepts of altered health states (2nd ed.). Philadelphia, PA: Lippincott Williams & Wilkins.

 

 

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