Blood and Lymph Disorder PDF

Pathophysiology (2) (MBS 214) Blood and Lymphatic Disorders Textbook; Pathophysiology for the Health Professions, C H A P T E R 17  Blood and Lymphatic Disorders Chapter outline:-  Review of the Blood & Blood Dyscrasias  Review of the Lymphatic System &Lympha...

Pathophysiology (2) (MBS 214) Blood and Lymphatic Disorders Textbook; Pathophysiology for the Health Professions, C H A P T E R 17  Blood and Lymphatic Disorders Chapter outline:-  Review of the Blood & Blood Dyscrasias  Review of the Lymphatic System &Lymphatic Disorders Learning objectives: After studying this chapter ,the student is expected to: 1.Define the terms describing abnormalities in the blood. 2. Describe the pathophysiology, etiology, manifestations, diagnostic tests, and treatment for blood disorders:  anemias  polycythemia  hemophilia A  disseminated intravascular coagulation  leukemia 3. Describe the pathophysiology, etiology, manifestations, diagnostic tests, and treatment for lymphatic disorders:  lymphomas  multiple myeloma.  Review of the Blood Components of blood and their functions. 1-Blood disorders of erythrocytes Anemia. o Definition o Types of anemias o General manifestations for all types of anemias o Pathophysiology of each type Polycythemia Erythrocytes or red blood cells (RBCs) Produced from red bone marrow from stem cell. Its life span is approximately 120 days. It is phagocytosed in the spleen or liver Biconcave, non-nucleated when mature and contain hemoglobin. The hormone erythropoietin stimulates its production in response to tissue hypoxia , which depend on the availability of many raw materials, including amino acids, iron, vitamin B12, vitamin B6, and folic acid.  Erythrocytes or red blood cells (RBCs) The size and structure are essential for easy passage through small capillaries. Hemoglobin : A protein ("globin") plus an iron molecule ("heme") which provides the red color. – Oxyhemoglobin is a bright red color, and is found in arterial blood – Deoxygenated hemoglobin (deoxyhemoglobin is dark or bluish- red in color and is found in venous blood. It is broken down into globin and heme – The iron return to bone marrow and liver – Excess iron can be stored – Bilirubin is transported by the blood to the liver where it is conjugated with glucuronide to make it more soluble, and then excreted in the bile.  Erythrocytes Normally RBCs constitute most of the cell volume in blood. Males :RBC:4.9-5.9/ million/mm3, hemoglobin:13.5-18g/100ml Females:RBC:4.2-5.2 million/mm3,hemoglobin:12-16g/100ml Other measures of erythrocyte: – Reticulocytes :may reveal inadequate production of RBCs – Hematocrit :( 35-50%)the proportion of cells (essentially the erythrocytes) in blood – Erythrocyte sedimentation rate(ESR) – Mean corpuscular volume (MCV) volume (size) of cell – Mean corpuscular hemoglobin (MCH) the average amount of hemoglobin per cell(indicates the oxygen-carrying capacity of the blood or reflect healthy of hemoglobin) – Measure % of O2 saturation of the blood ( pulse oximeter)using device applied on tip of the patient’s finger  Blood disorders of erythrocytes THE ANEMIAS :Definition:  A decrease in hemoglobin content, a decrease in the concentration of erythrocytes in the blood , or a combination of these factors, cause a reduction in oxygen transport in the blood  Decrease in the oxygen -carrying ability of the blood which may result from below normal concentrations of red blood cells or hemoglobin in the blood or both Deficiency of RBCs or hemoglobin The oxygen deficit leads to a sequence of events: Less energy -------less metabolism and reproduction The general manifestations of anemia: – Fatigue (excessive tiredness), pallor (pale face), dyspnea (increased effort to breathe), and tachycardia (rapid heart rate). – Decreased regeneration of epithelial cells causes : Digestive tract to become inflamed and ulcerated, leading to stomatitis (ulcers in the oral mucosa),inflamed and cracked lips, and dysphagia (difficulty swallowing) Hair and skin may show degenerative changes. – Severe anemia : the heart May lead to angina (chest pain) during stressful situations if the oxygen supply to the heart is sufficiently reduced. Chronic severe anemia may cause congestive heart failure.  Types of anemias 1. Iron Deficiency Anemia 2. Pernicious Anemia-Vitamin B12 Deficiency (Megaloblastic Anemia) 3. Aplastic anemia 4. Hemolytic anemia Sickle cell anemia Thalassemia  Iron Deficiency Anemia Microcytic Hypochromic Anemia 1- Insufficient iron , the synthesis of hemoglobin , thus reducing the amount of oxygen transported in the blood 2- Iron deficiency anemia is very common; occurs in all age groups and the proportion increases for pregnant women. Etiology An iron deficit can occur for many reasons:  Malnutrition where dietary intake of iron-containing vegetables or meat (protein) may be below the minimum requirement.  Chronic blood loss ( a bleeding ulcer, hemorrhoids, cancer, or excessive menstrual flow) causes less iron is recycled to maintain an adequate production of hemoglobin  Malabsorption syndromes such as ileitis and achlorhydria (lack of hydrochloric acid in the stomach)  Severe liver disease may affect both iron absorption and iron storage.  Underutilization of iron in some infections and cancers, where iron is present but is not well used, leading to low hemoglobin levels but high iron storage levels. Signs and symptoms of Iron Deficiency Anemia Mild are frequently asymptomatic. Moderate hemoglobin value drops, -Skin: Pallor, coldness, brittle hair, spoon shaped (concave) and ridged nails -Central: Fatigue, dizziness, and fainting(syncope) -GIT: Stomatitis and glossitis -Menstrual irregularities As the anemia becomes more severe – Heart : palpitations, tachycardia, angina, heart attack – Respiratory : dyspnea (shortness of breath) – Explain the signs of anemia that indicate compensation for hypoxia is occurring.? Diagnostic tests : Blood tests demonstrate – Low hemoglobin level – Low Hematocrit level, – Low mean corpuscular volume MCV & MCH -Reduction in stored iron, as indicated by:  Decreased serum ferritin, and serum iron. Microscopic examination the erythrocytes appear microcytic (small cell), hypochromic (less color) Treatment – The underlying cause must be identified and resolved if possible. The treatment and prognosis depend on the cause. – Iron-rich foods or iron supplements in the least irritating and most easily absorbable forms for the individual may be given. It is advisable to take iron with food to reduce gastric irritation and nausea.  Pernicious Anemia-Vitamin B12 Deficiency (Megaloblastic Anemia) A deficit of vitamin B12 leads to impaired maturation of erythrocytes owing to interference with DNA synthesis. Etiology: 1- Dietary insufficiency is rare because very small amounts of vitamin B12 are required. 2- Malabsorption is the most common cause due to lack of the intrinsic factor secreted from parietal cells of the stomach , may result from :  an autoimmune reaction,, particularly in older individuals;  from chronic gastritis, which is common in alcoholics  inflammatory conditions such as ileitis.  surgical procedures as gastrectomy, in which the parietal cells are removed, or resection of the ileum, which is the site of absorption. Signs and symptoms Basic manifestations of anemia, plus: 1. The tongue is typically enlarged, red, sore, and shiny. 2. Digestive discomfort, often with nausea and diarrhea (decrease Hcl ) 3. The neurologic effects include tingling or burning sensations (paresthesia) in the extremities or loss of coordination and ataxia Diagnostic tests 1-Microscopic examination of a peripheral blood smear. The erythrocytes appear macrocytic or megaloblastic with decreased count Granulocytes (neutrophils) are hyper-segmented and are decreased in number 2-The bone marrow is hyperactive, with increased numbers of megaloblasts 3-The vitamin B12 level in the serum is below normal. Treatment: Vitamin B12 by injections  Aplastic Anemia Impairment or failure of bone marrow, leading to loss of stem cells and pancytopenia Etiology Primary type : Unknown or idiopathic (the patients are middle-aged) Secondary type: o Myelotoxins, such as radiation, industrial chemicals (e.g., benzene), and drugs (e.g., chloramphenicol, phenytoin, and antineoplastic drugs) o Viruses, particularly hepatitis C o Autoimmune disease such as systemic lupus erythematosus (SLE) o Genetic abnormalities. Signs and symptoms In the majority of cases, the onset is insidious Manifestations include those of: 1. Anemia (pallor, weakness, and dyspnea) 2. Leukopenia, --- infections (recurrent/multiple & uncontrolled)) 3. Thrombocytopenia hemorrhages as petechiae (flat, red, pinpoint) on the skin and excessive bleeding. Diagnostic tests Blood counts indicate pancytopenia. A bone marrow biopsy may be required to confirm the cause of the pancytopenia. Treatment Prompt treatment of the underlying cause and removal of any bone marrow suppressants are essential to recovery of the bone marrow. Blood transfusion may be necessary if stem cell levels are very low. Bone marrow transplantation may be helpful in younger patients  Hemolytic Anemias Excessive destruction of RBCs, or hemolysis, leading to a low erythrocyte count and low total hemoglobin. Etiology : – genetic defects affecting structure, – Immune reactions, – changes in blood chemistry, – the presence of toxins in the blood, – infections such as malaria, transfusion reactions, and – blood incompatibility in the neonate (erythroblastosis fetalis). Two examples Sickle cell anemia Thalassemia Both are genetic disorders caused by errors in the genes for hemoglobin  Sickle cell anemia Inherited, abnormal form of hemoglobin, hemoglobin S. (HbS ). HbS when deoxygenated, it crystallizes and changes the shape of the RBC from a disc to “sickle,” shape. (sickling crisis ) The effects of sickling (4)  Sickle cell anemia Etiology. The inheritance pattern is recessive Very common in individuals from Africa and the Middle East. Individuals vary greatly in the severity of the anemia and the number of sickling crises. Sickle cell anemia : A condition where most of the normal hemoglobin (hemoglobin A [HbA]) is replaced by HbS, resulting in clinical signs of sickle cell anemia. Sickle cell trait; A condition where less than half the hemoglobin is the abnormal HbS, and therefore clinical signs occur only with severe hypoxia under unusual circumstances, for example, pneumonia or at high altitudes Diagnostic Tests.: Prenatal diagnosis: DNA analysis of the fetal blood. –(genetic screening) In children over 1 year of age, the diagnosis can be confirmed by the presence of sickled cells in peripheral blood and the presence of HbS. The bone marrow is hyperplastic, and more reticulocytes (immature RBCs) are released into the circulation. Carriers of the defective gene can be detected by a simple blood test (hemoglobin electrophoresis). – This identification is useful in alerting those with sickle cell trait to avoid severe hypoxia and sickling episodes (e.g., with severe anemia, surgery, or at high altitudes), as well as in assisting prospective parents in decision making about the risk of having an affected child. Treatment: The search continues for more effective drugs to reduce sickling. The use of hydroxyurea has reduced the frequency of crises and prolonged the life span for many, but is not effective for all patients. Dietary supplementation with folic acid (folate) is recommended even during asymptomatic periods. Avoidance of strenuous activity or high altitudes is helpful.. Children should be immunized against pneumonia, influenza, and meningitis. Continued prophylactic penicillin may be necessary for two groups; young children and adults with severe cases. Gene therapy is under investigation. Bone marrow transplant is effective, Improvements in care have extended the lifespan into middle age for many patients.  Thalassemia A genetic defect in which one or more genes for hemoglobin synthesis are missing or variant. – The amount of hemoglobin synthesized and the number of RBCs are reduced. – Damaging the RBCs leading to hemolysis and anemia. – In severe cases, splenomegaly, hepatomegaly, and hyperbilirubinemia. – The bone marrow is hyperactive, trying to compensate. Etiology: Most common genetic disorder; 80 -100,000 children are born annually; it occurs in two common forms.; Thalassemia beta: (autosomal dominant inheritance) more common, occurs frequently in people from Mediterranean countries , The alpha form is found in those of Indian, Chinese, or Southeast Asian descent. Signs and Symptoms: Usual signs of anemia and increased hemolysis. Child’s growth and development are impaired directly by the hypoxia and indirectly by the fatigue and inactivity. Hyperactivity in the bone marrow. Congestive heart failure develops. Diagnostic Tests: RBCs are varying in size An increase in erythropoietin levels. Iron overload exists. Prenatal diagnosis can be done by chorionic villus assay at 12 weeks or by amniocentesis at 16 weeks. Treatment Blood transfusions are the only treatment available at this time. Iron chelation therapy may be necessary to remove the excess iron from numerous transfusions. Administration of folate is also recommended. Bone marrow transplants have been curative in some children and are in clinical research trials. Patients with mild forms of the disease have a normal lifespan and those with moderate to severe disease live into their thirties with transfusions and chelation therapy.  Specific signs and symptoms Thalassemia hereditary hemolytic diseases caused by faulty hemoglobin synthesis, widespread in Mediterranean, African, and Asian countries.  POLYCYTHEMIA Increased red blood cell and other cells in bone marrow Two types;  Primary polycythemia, or polycythemia vera (PV),  Secondary polycythemia, or erythrocytosis; occurs in response to prolonged hypoxemia which triggers erythropoietin secretion (only RBCs level is high) : – chronic lung disease or – heart disease or – living at high altitudes.  Relative polychthemia: RBC number is normal but plasma volume is contracted  POLYCYTHEMIA VERA Commonly develops between the ages of 40 and 60 years, A neoplastic disorder of stem cell. Elevated levels of all three peripheral blood cell lines: RBCs, WBCs and platelets. Its prominent feature is an elevated absolute red cell mass. Is it inherited? NO – do not have family history of this disease  POLYCYTHEMIA VERA Pathophysiology  A type of bone marrow disease  Bone marrow makes too many red blood cells, and often in granulocytes and thrombocytes  Blood get too thick (increased blood volume and viscosity)  Blood vessels are distended ----- Hemorrhage  Blood flow is slow leading to frequent thromboses (clots) and infarctions throughout the body,  Blood pressure is elevated and the heart hypertrophied.  The spleen and liver are congested and enlarged. Signs and symptoms: Many don’t have noticeable signs & symptoms, or vague symptoms as headache, dizziness, fatigue, & blurred vision. Plethoric face (excess of body fluid) and cyanotic appearance (deep bluish-red tone of the skin and mucosa) Pruritus (Itching) is common, especially after exposure to hot water Blood pressure increases and dyspnea Unusual bleeding; nose or gums Complications : – Thromboses and infarctions may affect the extremities, liver, or kidneys as well as the brain or the heart. – Congestive heart failure frequently develops because of the increased work load resulting from the increased volume and viscosity of blood. – Severe joint pain and kidney damage – High levels of uric acid resulting from cell destruction Diagnostic tests: Polycythemia Vera, 1- Blood tests might reveal: Abnormal CBC Hematocrit elevated Elevated levels of hemoglobin. 2- Bone marrow aspiration or biopsy Bone marrow is hyper cellular, with the red marrow replacing some fatty marrow. Secondary polycythemia : Oxygen levels in the blood; arterial blood gasses (ABG's). Measurement of erythropoietin and red blood cell mass levels. Additional diagnostic tests may include: Chest X-ray Treatment Polycythemia Vera is a chronic condition that can't be cured. In many cases, treatment can reduce the risk of complications from polycythemia Vera and ease signs and symptoms Treatment focuses on reducing amount of blood cells. – Drugs or radiation may be used to suppress the activity of the bone marrow. – There is significant risk that fibrosis or leukemia may develop with these methods. – Periodic phlebotomy, or removal of blood, may be used to minimize the possibility of thromboses or hemorrhages.  Blood Types An individual’s blood type (e.g., ABO and Rh groups) is determined by the presence of specific antigens on the cell membranes of erythrocytes. An antigen antibody reaction would occur with an incompatible blood transfusion, resulting in agglutination (clumping) and hemolysis of the recipient’s RBCs. – Rh factor, an inherited factor which may cause blood incompatibility if the mother is Rh-negative and the fetus is Rh positive (erythroblastosis fetalis or hemolytic disease of the newborn- may result in fetal death).  Blood Clotting Hemostasis consists of three steps: The immediate response of a blood vessel to injury is vasoconstriction or vascular spasm. This decreases blood flow. Second, thrombocytes tend to adhere to the underlying tissue at the site of injury and, if the blood vessel is small, can form a platelet plug in the vessel. The blood-clotting or coagulation mechanism is required in larger vessels, by which the clotting factors that are present in inactive forms in the circulating blood are activated through a sequence of reactions  Blood Clotting mechanism Thrombocytes, (platelets), are an essential part of the blood-clotting process or hemostasis Thrombocytes can also initiate the coagulation process. The circulating clotting factors are produced primarily in the liver. – Vitamin K, a fat-soluble vitamin, is required for the synthesis of most clotting factors. – Calcium ions are essential for many steps in the clotting process. FIGURE 17-6 Hemostasis and anticoagulant drugs.  BLOOD-CLOTTING DISORDERS Causes of abnormal bleeding (delay clotting): 1. Thrombocytopenia 2. Defective platelet function is associated with uremia (end-stage kidney failure) 3. Vitamin K deficiency. 4. Chemotherapy & radiation treatment 5. Anticoagulant drugs(warfarin) 6. Liver disease 7. Hemorrhagic fever viruses as Ebola virus 8. Inherited defects  WARNING SIGNS OF EXCESSIVE BLEEDING  Persistent bleeding from the gums or repeated nosebleeds  Skin appearance ;  Petechiae—pinpoint flat red spots on skin or mucous membranes  Frequent purpura and ecchymosis—large, purplish red or greenish areas on the skin  Abnormal persistent bleeding following trauma  Bleeding into a joint—hemarthroses —swollen, red, and painful  Coughing up blood—hemoptysis—bright red flecks in sputum  Vomiting blood—hematemesis—often coarse brown particles (coffee grounds); may be red  Blood in feces—often black (tarry) or occult (hidden)  Anemia  Feeling faint and anxious, low blood pressure, rapid pulse  BLOOD-CLOTTING DISORDERS Blood clotting disorders : – Hemophilia – Disseminated intravascular coagulation  Hemophilia Pathophysiology o An inherited Sex-linked clotting disorder, o genetic disorder characterized by inadequate synthesis of clotting factors, transmitted as an X-linked recessive trait and therefore, it is manifest in men but is carried by women, who are asymptomatic o 90% of hemophiliac patients have type A, Hemophilia A, or classic hemophilia o Hemophilia A; Occurs due to a deficiency or abnormality of clotting factor VIII o Hemophilia B; deficiency in factor IX o Hemophilia C; deficiency in factor XI Signs and symptoms Prolonged or severe hemorrhage occurs following minor tissue trauma and hematomas (bruises) is common. Spontaneous hemorrhage into joints (hemarthrosis -swelling of joint, tender, and hot) may occur. Blood may appear in the urine (hematuria) or feces because of bleeding in the kidneys or digestive tract. Diagnostic tests: Coagulation time is prolonged. Serum levels of factor VIII are low. Treatment: Replacement therapy for factor VIII.  Disseminated Intravascular Coagulation (DIC) Pathophysiology A condition begins with excessive clotting. – where blood clots form throughout the body's small blood vessels. – The increased clotting consumes and depletes the platelets and clotting factors needed to control bleeding, causing excessive bleeding. Signs and symptoms: Manifestations depend on the underlying cause. Hemorrhage is the MOST COMMON critical problem. and excessive bleeding (sites may be present on the skin or mucosa) Ischemia and multiple infarctions due to vascular occlusions Organ failure and shock.  Leukocytes The five types of leukocytes vary in physical characteristics and functions Some examples of FIGURE 17-1 Components of blood and their functions. WBCs are visible as large, nucleated cells (purple stain) in the blood smear Expected Ranges Neutrophil (%) 50-70 Eosinophil (%) 1-4 FIGURE 17-5 Normal blood cells. Basophil (%) 0.1 -many erythrocytes, discs with faded centers; Monocyte (%) 2-8 - leukocytes, larger size with nuclei; stained purple, various types; Lymphocyte (%) 20-40 -thrombocytes, the small dark pieces.  Blood disorders of leukocytes LEUKEMIAS Definition: A neoplastic disorder involving one or more types of leukocyte that are present as: -blast cells (undifferentiated, immature, nonfunctional cells ) -multiply uncontrollably in the bone marrow, and large quantities are released as such into the general circulation o As the numbers of leukemic cells increase, they infiltrate the lymph nodes, spleen, liver, brain, and other organs  The two major classification of leukemia; Acute and chronic Acute leukemia: abrupt onset Acute lymphocytic leukemia (ALL), the most common childhood cancer 80%, (between the ages of 2 and 5 years ) Acute myelogenous leukemia (AML) is common in adults; insidious onset, milder signs. Etiology: Identify individuals who are considered at high risk for development of leukemia? – Individuals with chromosomal abnormalities (in children with Down syndrome) – in adults, including ; exposure to radiation, chemicals. develop years after a course of chemotherapy Diagnostic tests: Peripheral blood smears : – immature leukocytes , numbers of WBCs greatly increased (