Blood and Blood-Forming Organs Diseases and Disorders Chapter 7 Blood and Blood-Forming Organs Diseases and Disorders 1

Anatomy and Physiology Hematologic system Major functions of blood: Transport nutrients to cells Aid removal of wastes Average adult has 5 to 6 liters of circulating blood 2

Blood Components 3

Anatomy and Physiology Erythrocytes Normal count: 4.2 to 6.3 million Life span: 120 days Form in bone marrow and do not reproduce 4

Anatomy and Physiology Hemoglobin important in oxygen transport Normal hemoglobin: Male 13.5 to 18 hemoglobin in grams (g)/100 milliliters (ml) Female 12 to 16 g/100 ml 5

Anatomy and Physiology Leukocytes protect individual from infection Normal count: 4,500 to 11,000 mm3 Platelets Also known as thrombocytes Important in blood clotting 150,000 to 350,000 mm3 Note: normal values may vary some from different laboratories or sources 6

Hematology White Blood Cell WBC Non-Blacks: 4000 - 10,000/ml (4-10K/mL) Blacks 2800 - 10,000/mL (2.8 -10K/ul) Hemoglobin Hgb M: 13.5-17.5 g/dL F: 12.0-16.0 g/dL Glysolated hemoglobin HgbA1c 5.6 - 7.5 % of total Hgb Hematocrit Hct M: 41-53% F: 36-46% Red blood cell RBC M: 4.5-5.9 x 106 cells/mL F: 4.0-5.2 x 106 cells/mL Mean corpuscular volume MCV 80-100 fL Mean corpuscular hemoglobin MCH 26-34 pg/cell Mean corpuscular hemoglobin concentration MCHC 31.5-36.3 gm/dL Reticulocytes Retic 33-137 x 103 cells/mL Platelets Plt 150-400 x 103/mL Erythrocyte sedimentation rate ESR 0-20 mm/hr http://missinglink.ucsf.edu/lm/IDS_106_LowerGI/Lower%20GI/mainpages/normallabvalues.htm

Anatomy and Physiology Blood-forming organs: Lymph nodes Bone marrow Spleen Liver—the embryo makes blood cells at 6 weeks Lymph system protects against pathogens 8

Anatomy and Physiology Bone marrow Major blood cell producer Spleen produces lymphocytes, plasma cells, and antibodies Filters microorganisms from blood Liver produces prothrombin and fibrinogen for blood clotting 9

vitamin K and Liver Disease The liver stores vitamins and minerals to be used as needed including all the fat-soluble vitamins;(A, B12, D, E and K). .Vitamin K is a fat-soluble organic compound that the body needs to remain healthy. Although bacteria in the human intestine make some vitamin K, it is not nearly enough to meet the body's needs, so people must get most of their vitamin K from foods in their diet. Hepatitis C Cirrhosis; Vitamin K Deficiencies .The liver needs vitamin K to make factors that regulate blood clotting .Vitamin K deficiency is extremely rare in healthy people. It can, however, occur in individuals who have significant liver damage or disease disorders that interfere with the absorption of nutrients from the intestine. .

Liver disease (cirrhosis) causes a decrease in bile salt synthesis, leading to impaired absorption and Vitamin K deficiency. The liver makes a number of coagulation (clotting) factors including prothrombin and fibrinogen. Most of these require the presence of vitamin K to function normally. Vitamin K, as a fat-soluble vitamin, in turn requires bile salts to be absorbed properly by the body. If the liver is impaired and does not produce enough bile this will have an effect on the capacity to clot blood; increasing the risk of bleeding.

1-Vitamin K is necessary for the formation of prothrombin and other blood-clotting factors in the liver, and it also plays a role in bone metabolism. ,2-A form of the vitamin is produced by bacteria in the colon and can be utilized to some degree.

Common Signs and Symptoms Erythrocytopenia Decrease in RBCs leading to anemia Symptoms: Fatigue Headache Low RBCs Pallor Shortness of breath 13

Common Signs and Symptoms Erythrocytosis Increased RBCs Symptoms: High RBCs Reddened skin tones Bloodshot eyes Increased blood volume and pressure Increased blood volume of heart 14

Common Signs and Symptoms Leukocytopenia Decreased white blood cells Weakens immune system Leukocytosis Increased white blood cells Normal response to acute infections 15

Common Signs and Symptoms Thrombocytopenia Decreased platelet count leading to coagulation problem Symptoms: Petechiae Small hemorrhages in skin Ecchymoses Large areas of bruising or hemorrhage Epistaxis, also called a nosebleed Bleeding in mouth, gums, and mucous membranes 16

Common Signs and Symptoms Thrombocytosis Increase in platelets Uncommon Usually no serious side effects 17

Diagnostic Tests Complete blood count with differential and indices Biopsy of blood-forming organs Hematocrit (Hct) reflects amount of red cell mass as proportion of whole blood Hemoglobin (Hgb) reflects blood’s oxygen-carrying potential 18

Complete Blood Count

Diagnostic Tests Bleeding time determines platelet disorders E.g., hemophilia, thrombocytopenia, disseminated intravascular coagulation Prothrombin time (PT), partial thromboplastin time (PTT), and international normalized ratio (INR) measure blood’s ability to clot 20

Diagnostic Tests Bone marrow donation and transplant Blood Tests 21

Bone marrow aspirations Bone marrow biopsy                                                                                                                                                        http://www.youtube.com/watch?v=PlFhC1egESI http://www.youtube.com/watch?v=of_zdRz5TXg Bone marrow aspirations

Coagulation Parameters Prothrombin time PT 11-14 seconds Partial thromboplastin time PTT 25-35 seconds International normalized ratio INR 0.8 to 1.2

Disorders of Red Blood Cells Anemia Decrease in oxygen-carrying ability of RBC Symptoms: Pallor Fatigue Shortness of breath Tachycardia Headache Irritability Syncope 24

Disorders of Red Blood Cells Iron deficiency anemia Loss of iron or inadequate intake of iron Causes: Blood loss Low dietary intake Treatment: Increase dietary intake of iron 26

Disorders of Red Blood Cells Folic acid deficiency anemia Folic acid needed for maturation of RBCs Causes: Poor diet Overcooking of vegetables Overconsumption of alcohol Treatment: Increase folic acid intake by eating green and yellow vegetables 27

Disorders of Red Blood Cells Pernicious anemia Lack of intrinsic factor leading to inadequate absorption of vitamin B12 Treatment: Monthly injections of vitamin B12 for life 28

Uses Cyanocobalamin is a man-made form of vitamin B12 used to treat low levels (deficiency) of this vitamin. Vitamin B12 helps your body use fat and carbohydrates for energy and make new protein. It is also important for normal blood, cells, and nerves. Most people get enough vitamin B12 in their diet, but a deficiency may occur in certain health conditions (e.g., poor nutrition, stomach/intestinal problems, infection, cancer). Serious vitamin B12 deficiency may result in anemia, stomach problems, and nerve damage. How to use Vitamin B-12 injection Before using, check this product visually for particles or discoloration. If either is present, do not use the liquid.

Benefits of Vitamin B Injections:                                                   *BoostEnergy *Increases activity of nervous system *Essential for acceleration of cell renewal *Enhances red blood cell production *Assists in stress management *Improves concentration and memory *Increases metabolism to burn fat *Removes and transports fat out of the body

Disorders of Red Blood Cells Hemolytic anemia Destruction of RBCs related to antibody–antigen reaction Disorder of immune system leading to destruction of erythrocytes Treatment: Exchange transfusion and/or splenectomy 31

Severe Anemia Infants are severely anemic with hemoglobins as low as 5 g/dl. This degree of anemia results in severe congestive heart failure that results in massive edema. The photo shows an infant with hydrops fetalis. Hydrops fetalis literally means bloated with fluid. The hepatosplenomegaly is also evident here. Infants will frequently have effusions in the pleural and pericardial cavities.

Disorders of Red Blood Cells Sickle cell anemia Hereditary Found in African American race Abnormal sickle shape of erythrocyte Does not allow cell to travel smoothly through vessels Symptomatic treatment No cure The next slides explain and show some complications from sickle cell 33

 Sickle-cell disease is the most prevalent genetic disease in the Brazilian population. Lower limb ulcers are the most frequent cutaneous complications, affecting 8% to 10% of the patients. These ulcers are usually deep and may take many years to heal. Evidence about the effectiveness of systemic or topical treatment of these wounds is limited, apart from stabilization of the anemia - See more at: http://www.o-wm.com/content/negative-pressure-therapy-complex-wounds-patients-sickle-cell-disease-case-study#sthash.h6iYRYCC.dpuf

Aplastic Crises In Sickle Cell Anemia

Disorders of Red Blood Cells Hemorrhagic anemia Loss of whole blood Also called blood loss anemia Complication is hypovolemic shock Symptoms include: Dizziness, fainting, thirst Treatment Stop bleeding Oxygen Restore blood volume 37

Disorders of Red Blood Cells Aplastic anemia Failure of bone marrow to produce blood components Causes: Chemotherapy Radiation Viruses Toxins Treatment: Avoid causative agent Bone marrow transplantation Transfusions 38

Disorders of Red Blood Cells Polycythemia Too many blood cells Symptoms: Enlarged spleen Reddened mucous membranes Bloodshot eyes Deep red color on palms Treatment: Donate blood at regular intervals to reduce blood volume 39

Polycythemia

Disorders of White Blood Cells Mononucleosis Caused by virus Symptoms: Fatigue Sore throat Swollen glands 42

Disorders of White Blood Cells Leukemia Malignant neoplasm of blood-forming organs Abnormal production of immature leukocytes May be acute or chronic Acute forms affect children, progress rapidly, and may be fatal ---Most childhood leukemias are acute lymphocytic leukemia (ALL). Most of the remaining cases are acute myeloid leukemia (AML). 44

About Leukemia Leukemia is a type of cancer that affects the body's white blood cells (WBCs). Normally, WBCs help fight infection and protect the body against disease. But in leukemia, WBCs turn cancerous and multiply when they shouldn't, resulting in too many abnormal WBCs, which then interfere with organ function. If too many lymphoblasts (a certain type of WBC) are produced, a child will develop acute lymphoblastic, or lymphoid, leukemia (ALL). This is the most common type of childhood leukemia, affecting about 75% of kids with this cancer of the blood cells. Kids ages 2 to 8 are more likely to be affected, but all age groups can develop ALL.

Children who have inherited certain genetic problems (such as Li-Fraumeni (The syndrome is linked to germline mutations of the TP53 tumor suppressor gene) syndrome, Down syndrome, Klinefelter syndrome, neurofibromatosis, (Neurofibromatosis is a genetic disorder that disturbs cell growth in your nervous system, causing tumors to form on nerve tissue) ataxia telangiectasia, or Fanconi anemia (The Fanconi anemia (FA) pathway is one of the DNA damage response mechanisms frequently lost in cancer. also have a higher risk of developing leukemia, as do those who are receiving medicines to suppress their immune systems after organ transplants. Kids who have received radiation or chemotherapy for other types of cancer also have a higher risk, usually within the first 8 years after treatment.

Disorders of White Blood Cells Leukemia Chronic forms affect older adults, are often asymptomatic, and may not be fatal Classified as: Myelogenous Affecting bone marrow Lymphocytic Affecting lymph nodes 47

Disorders of White Blood Cells Leukemia Symptoms: Fatigue Headache Sore throat Dyspnea Bleeding of mucous membranes of mouth and gastrointestinal (GI) system Bone and joint pain Enlargement of lymph nodes, liver, and spleen Infections common 49

Disorders of White Blood Cells Leukemia Diagnosis by bone marrow biopsy Treatment: Aggressive chemotherapy Once in remission, bone marrow transplant to replace neoplastic tissue with normal tissue Remission at 50% 50

Bone marrow biopsy

Disorders of White Blood Cells Hodgkin’s disease Most common lymphoma Symptoms: Painless enlargement of lymph nodes in neck Weight loss Fever Primarily affects young adults Average age of 35 52

For Hodgkin and NHL, the symptoms are the same For Hodgkin and NHL, the symptoms are the same. However, one key feature in Hodgkin Lymphoma is the Pel-Ebstein fever or cyclic fever, which increases and then suddenly decreases within 1 – 2 weeks, and starts all over again. A very important symptom in all types of lymphomas is the painless enlargement of the lymph nodes (in the neck, mandible, axillary, shoulder, etc.).

Then, fever, chills, night sweats and weight loss might ensue Then, fever, chills, night sweats and weight loss might ensue. As the disease progresses, the enlarged lymph nodes could become painful, leading to what is referred to as “painful lymphadenopathy”. Some patients could also experience intractable back pain that doesn’t seem to be relieved by any medications. Also, bleeding under the skin (ecchmymoses, purpurae or petechiae) could also be observed in patients suffering from lymphomas.

Disorders of White Blood Cells Hodgkin’s disease Cause thought to be viral Diagnosis by presence of Reed–Sternberg cell in lymphatic tissue Treatment: Radiation Chemotherapy If in remission for 5 years or more, complete cure possible 55

Disorders of White Blood Cells Non-Hodgkin’s lymphoma (NHL) Lymphomas lacking Reed–Sternberg cell Symptoms: Painless enlargement of lymph nodes of neck, axilla, and inguinal areas Fever Night sweats Weight loss 56

Other Clues In Hodgkin Lymphoma, the affected lymph nodes are contiguous. In other words, they follow a specific chronological pattern” starting in the shoulders, then the neck, then the chest. Non-Hodgkin lymphomas however could arise anywhere and affect any type of lymph nodes at a given time, with no specific pattern.

Treatment for Non-Hodgkin’s Treatment for lymphoma that causes signs and symptoms If your non-Hodgkin's lymphoma is aggressive or causes signs and symptoms, your doctor may recommend treatment. Options may include: Chemotherapy. Chemotherapy is drug treatment — given orally or by injection — that kills cancer cells. Chemotherapy drugs can be given alone, in combination with other chemotherapy drugs or combined with other treatments. Radiation therapy. Radiation therapy uses high-powered energy beams, such as X-rays, to kill cancerous cells and shrink tumors. During radiation therapy, you're positioned on a table and a large machine directs radiation at precise points on your body. Radiation therapy can be used alone or in combination with other cancer treatments.

Cont. Stem cell transplant. A stem cell transplant is a procedure that involves very high doses of chemotherapy or radiation with the goal of killing the lymphoma cells that may not be killed with standard doses. Later, healthy stem cells — your own or from a donor — are injected into your body, where they can form new healthy blood cells. Medications that enhance your immune system's ability to fight cancer. Biological drugs help your body's immune system fight cancer. Rituximab (Rituxan) is a type of monoclonal antibody that attaches to B cells and makes them more visible to the immune system, which can then attack. Rituximab lowers the number of B cells, including your healthy B cells, but your body produces new healthy B cells to replace these. The cancerous B cells are less likely to recur.

Cont. Medications that deliver radiation directly to cancer cells. Radioimmunotherapy drugs are made of monoclonal antibodies that carry radioactive isotopes. This allows the antibody to attach to cancer cells and deliver radiation directly to the cells. Two radioimmunotherapy drugs — ibritumomab (Zevalin) and tositumomab (Bexxar) — are used to treat lymphoma.

Disorders of White Blood Cells Multiple myeloma Malignant neoplasm of plasma cells or B-lymphocytes Increases with age Peaks in 70s Plasma cells multiply abnormally in bone marrow 61

Disorders of White Blood Cells Multiple myeloma Diagnosis by honeycombed bone pattern, hypercalcemia, Bence Jones protein found in blood and urine, and bone marrow biopsy Treatment: Chemotherapy Radiation Not effective Poor prognosis 62

myeloma Multiple myeloma causes cancer cells to accumulate in the bone marrow, where they crowd out healthy blood cells. Rather than produce helpful antibodies, the cancer cells produce abnormal proteins that can cause kidney problems. Treatment for multiple myeloma isn't always necessary. If you're not experiencing signs and symptoms, you may not require treatment. If signs and symptoms develop, a number of treatments can help control your multiple myeloma

Disorders of Platelets Hemophilia X-linked hereditary bleeding disorder Several types Type A Most common Male children from asymptomatic mothers Lack protein necessary for clot formation 64

Disorders of Platelets Hemophilia Symptoms: Epistaxis Bruising Prolonged bleeding Diagnosis by blood test 65

Disorders of Platelets Hemophilia Treatment: Prevention of injury Treat symptoms Blood transfusions Concentrated form of clotting protein No cure 66

Hemophilia usually is inherited Hemophilia usually is inherited. "Inherited” means that the disorder is passed from parents to children through genes. The two main types of hemophilia are A and B. If you have hemophilia A, you're missing or have low levels of clotting factor VIII (8). About 8 out of 10 people who have hemophilia have type A. If you have hemophilia B, you're missing or have low levels of clotting factor IX (9).

Rarely, hemophilia can be acquired Rarely, hemophilia can be acquired. "Acquired” means you aren't born with the disorder, but you develop it during your lifetime. This can happen if your body forms antibodies (proteins) that attack the clotting factors in your bloodstream. The antibodies can prevent the clotting factors from working.

Disorders of Platelets Thrombocytopenia Also known as thrombocytopenia purpura Decrease in platelets leading to inability to normally clot blood Symptoms: Abnormal bleeding in skin, mucous membranes, and internal organs Petechiae 69

Disorders of Platelets Thrombocytopenia Symptoms: Ecchymoses GI hemorrhages Epistaxis Hematuria 71

Disorders of Platelets Thrombocytopenia Diagnosis by platelet count and bleeding time Treatment: Avoid tissue trauma to reduce bleeding Vitamin K Transfusions of platelets Splenectomy 72

Disorders of Platelets Disseminated intravascular coagulation (DIC) Abnormal clotting followed by abnormal bleeding Usually follows major trauma E.g., complicated childbirth, surgery, tissue destruction, septicemia, snakebite, shock Multiple clots in capillaries Life-threatening 73

Some diseases and conditions can cause clotting factors to become overactive, leading to DIC. These diseases and conditions include: Sepsis (an infection in the bloodstream) Surgery and trauma Cancer Serious complications of pregnancy and childbirth Examples of less common causes of DIC are bites from poisonous snakes (such as rattlesnakes and other vipers), frostbite, and burns.

DIC can occur in the following conditions: Solid tumors and hematologic malignancies (particularly acute promyelocytic leukemia) Obstetric complications: abruptio placentae, pre-eclampsia or eclampsia, amniotic fluid embolism, retained intrauterine fetal demise, septic abortion Massive tissue injury: severe trauma, burns, hyperthermia, rhabdomyolysis, extensive surgery Sepsis or severe infection of any kind (virtually infections by any microorganism can cause DIC, though bacterial infections are the most common): bacterial (Gram-negative and Gram-positive sepsis), viral, fungal, or protozoan infections Transfusion reactions (i.e., ABO incompatibility hemolytic reactions) Severe allergic or toxic reactions (i.e. snake or viper venom) Giant hemangiomas (Kasabach-Merritt syndrome)

Disorders of Platelets DIC Symptoms: Petechiae Ecchymosis Hematoma Hematuria GI bleeding Hematemesis Blood in stool Treatment: Heparin or infusion of platelets 76

Rare Diseases Thalassemia Von Willebrand’s disease ( Lymphosarcoma Primarily affects people of Mediterranean descent Fragile, thin RBCs form defective hemoglobin Von Willebrand’s disease ( Hereditary, congenital Deficiency in clotting factor and platelet function Lymphosarcoma A type of lymphoma Symptoms similar to Hodgkin’s disease 77

Thalassemias (thal-a-SE-me-ahs) are inherited blood disorders Thalassemias (thal-a-SE-me-ahs) are inherited blood disorders. "Inherited" means that the disorder is passed from parents to children through genes.  Thalassemias affect males and females. The disorders occur most often among people of Italian, Greek, Middle Eastern, Southern Asian, and African descent. Severe forms usually are diagnosed in early childhood and are lifelong conditions

Thalassemias (thal-a-SE-me-ahs) are inherited blood disorders Thalassemias (thal-a-SE-me-ahs) are inherited blood disorders. "Inherited" means that the disorder is passed from parents to children through genes.  Thalassemias cause the body to make fewer healthy red blood cells and less hemoglobin (HEE-muh-glow-bin) than normal. Hemoglobin is an iron-rich protein in red blood cells. It carries oxygen to all parts of the body. Hemoglobin also carries carbon dioxide (a waste gas) from the body to the lungs, where it's exhaled. People who have thalassemias can have mild or severe anemia (uh-NEE-me-uh). Anemia is caused by a lower than normal number of red blood cells or not enough hemoglobin in the red blood cells.

Von Willebrand Normally, when one of your blood vessels is injured, you start to bleed. Small blood cell fragments called platelets (PLATE-lets) clump together to plug the hole in the blood vessel and stop the bleeding. Von Willebrand factor acts like glue to help the platelets stick together and form a blood clot.

[lim-foh-sahr-koh-muh] lymphosarcoma [lim-foh-sahr-koh-muh] a malignant tumor in lymphatic tissue, caused by the growth of abnormal lymphocytes. Lymposarcoma

Effects of Aging Age-related changes in other systems (e.g., immune, digestive) leave older adults more susceptible to infections and nutritionally related blood disorders Decreased iron Most common disorder is anemia Poor nutrition 82