Lecture 11 Flashcards
Plasma
Fluid component of blood
Blood composition and function
Red cells, leukocytes, and platelets; carries antibodies, oxygen, nutrients, hormone , and CO2 plus other waste products
Red blood cell function
Oxygen/Carbon Dioxide exchange
(the more red blood cells the more oxygen you can carry); Most numerous cells in the blood
Leukocytes (WBC) function and types
Immune functions; Neutrophils (Most numerous – first line), Monocytes (Phagocytic Macrophages), Eosinophils (Allergy, parasitic infections), Lymphocytes (Adaptive Immunity), and Basophils (Parasitic infections)
Platelet function
Hemostasis
Stem cells
Precursor cells in bone marrow that differentiate to form red cells, white cells, and platelets (any cell) - Hematopoietic stem cells differentiate into any blood cell type
Erythroblast
Precursor cells in bone marrow
Hemoglobin
An oxygen-carrying protein formed by the developing red cell
Ganulocytes/ Polymorphpnucleargraulocytes
PMN - Eosinophils, Basophils, Neutrophils
Where are Lymphocytes produced?
Mainly in lymph nodes and spleen; some are produced in bone marrow
Neutrophils
The first line of defence (Most numerous in adults,
Makeup 60-70% of total circulating WBC, Actively phagocytic, Predominant in inflammatory reactions)
Monocytes
3-5% of leukocytes (Increased in certain types of chronic infection, Circulate to sites of inflammation, Transition to Macrophages (APC), Infection/tissue repair)
Eosinophils/Basophils
Present in low numbers (Increased in allergic reactions and Increased in presence of animal–parasite infections)
Lymphocytes
15-20% of leukocytes (T/B cells, seen predominantly in children, Mostly located in lymph nodes, spleen, and lymphoid tissues (some in circulation plus lymphatic system), cell-mediated and humoral defence reactions)
Platelets
Essential for blood coagulation, Much smaller than leukocytes, Represent bits of the cytoplasm of megakaryocytes, the largest precursor cells in bone marrow, Short survival, about 10 days
Hematopoiesis
Formation and development of blood cells; bone marrow replenishes blood cells (damage/age)
Substances necessary for hematopoiesis
Protein, Folic Acid, Vitamin B12 (required for DNA synthesis), Iron (Decreased RBC production if any of these are lacking)
How is RBC production regulated
Oxygen content in blood which stimulates hormone (epo) release from kidneys
True or False: High reticulocyte count indicates the body is creating a lot of RBC
True, they leave bone marrow and differentiate into RBC in circulation
Red cell production
Regulated by oxygen content of the arterial blood – stimulated by erythropoietin
White cell production
Regulated by Interleukin levels/ response to infection – complex
Heme
Porphyrin ring that contains an iron atom
Globin
The largest part of hemoglobin; forms different chains designated by Greek letters such as alpha, beta, gamma, delta, and epsilon
Porphyrin ring
Produced by the mitochondria; iron is inserted to form heme
Reticulocyte
A young red cell without a nucleus, but retains some organelles; identified by special strains found in bone marrow (matures in 24-48)
Globin chains
Produced by ribosomes; joined to heme to form a hemoglobin unit (4 subunits to complete hemoglobin tetramer)
Red blood cell degradation
Worn-out red cells are removed in the spleen, Hemoglobin is degraded and excreted as bile by the liver, The porphyrin ring cannot be salvaged, Globin chains break down and are used to make other proteins, and Iron is extracted and saved to make new hemoglobin
Reduced oxygen supply stimulates
Erythropoiesis (erythropoietin)
High partial pressure oxygen in lungs
Promotes binding
Low partial pressure oxygen in tissues
Promotes release
Methemoglobin Iron
Fe 3+, not in ferrous state, can’t bind oxygen, inherited disorder or response to toxic agents
Carboxyhemoglobin
Binds CO with high affinity (200x stronger than oxygen), blocks oxygen binding, products of incomplete combustion
Where are Iron reserves stored?
Liver, bone marrow, and spleen
What do Duodenal cells produce?
Hepcidin to block uptake by duodenal cells and interferes with iron transport
Hemochromatosis
Common genetic disease transmitted as an autosomal recessive trait – chronically absorbs too much iron
Reasons for Iron overload
Patients who take iron supplements chronically, or have blood disorders where there is a loss of RBC destruction (sickle cell), overload due to inability to reduce iron levels
Treatment for Hemochromatosis
Periodic removal of blood (phlebotomy) until iron stores are depleted, and use of iron chelation treatment to remove iron
Anemia causes
Insufficient raw materials (Iron deficiency, vitamin B12 deficiency, Folic acid deficiency), Inability to deliver adequate red cells into circulation due to marrow damage or destruction (aplastic anemia), excessive loss of red cells
Hemorrhage
External blood loss
What do Sickle cell and thalassemia cause?
Shortened survival of red cells in circulation
Hereditary hemolytic anemia
Defective red cells
Normocytic anemia
Normal size and appearance
Macrocytic anemia
Cells larger than normal impaired (folic acid and Vitamin B12 deficiency)
Microcytic anemia
smaller cells (thalassemia)
Hypochromic anemia
Reduced hemoglobin content
Hypochromic microcytic anemia
Smaller than normal and reduced hemoglobin content
Iron-deficiency Anemia
The most common type; Hypochromic microcytic anemia (not enough iron);
When does Iron-deficiency Anemia happen
This happens when there are a lack of iron in the diet, rapids periods of growth in infants, inadequate reutilization of iron, chronic infection/inflammation, cancers, and loss of blood (GI tract, excessive menstrual bleeding, too frequent blood donations)
Laboratory tests in blood for iron deficiency
Serum ferritin (low), Serum iron (low), and Serum iron-binding capacity (high)
Iron-Deficiency Anemia Treatment
Learning the cause of anemia, treatment on cause than symptoms, administering supplementary iron
Vitamin B12 deficiency anemia
Those who are vegetarian are at risk; found in meat, milk, and foods rich in animal proteins; For structural and functional integrity of the nervous system; deficiency may lead to neurologic disturbances
Folic acid
Green leafy vegetables and animal protein foods; are required for normal hematopoiesis and normal maturation of many other types of cells
Absence or deficiency of vitamin B12 or folic acid
Mature red cells are larger than normal or macrocytes; corresponding anemia is called macrocytic anemia, Leukopenia (low WBC), thrombocytopenia (low platelets), Abnormal red cell maturation or megaloblastic erythropoiesis
Folic Acid Deficiency Anemia Pathogenesis
Inadequate diet: Encountered frequently in chronic alcoholics
Poor absorption caused by chronic intestinal disease
Occasionally occurs in pregnancy with increased demand for folic acid
Pernicious Anemia (macrocytic anemia)
Lack of intrinsic factor (B12); causes included gastric mucosal atrophy, Autoantibodies directed against gastric mucosal cells and intrinsic factor, Surgery to remove sections of the stomach, and Chronic intestinal diseases (Crohn’s, IBD)
Pernicious Anemia treatment
Increased oral dose (B12 supplements) or Intramuscular injections
Conditions that depress bone marrow function
Anemia of chronic disease: Mild suppression of bone marrow function (parvoirus B19), Aplastic anemia (Marrow injured by radiation, anticancer drugs or chemicals, Autoantibodies, CTL autoimmunity)
What does bone marrow suppression affect?
WBC and platelets - Pancytopenia (anemia, leukopenia, thrombocytopenia)
Bone marrow treatment
Depends on the cause; Blood and platelet transfusions, Immunosuppressive drugs, Hemopoietic stem cell transplant in highly selected cases of aplastic anemia, or no specific treatment
Hereditary hemolytic anemia
Genetic abnormality prevents normal survival, Abnormal shape (Hereditary spherocytosis; These cells have no central pallor), Abnormal hemoglobin (Hemoglobin S (sickle hemoglobin) or hemoglobin C), Defective hemoglobin synthesis (Thalassemia minor and major; globin chains are normal, but synthesis is defective)
Thalassemia
Defective synthesis of alpha or beta globulin causing a lack of hemoglobin production
Alpha – (4 genes)
1- no change 2 -trait with mild disease, 3 severe disease, 4 – incompatible with life (hydrops fetalis)
Unstable Beta tetramers
Defective Oxygen exchange; formed by lack of alpha and excess beta chains
Beta – (2 genes)
Heterozygous-mild, homo-severe
Sickle cell
Hemoglobin S (beta Hgb point mutation); Present in areas where Malaria is/was common; Constant sickling wears out cells and sickled cells are targeted for early destruction by the spleen, cells can also form blockages, chronic joint pain also occurs
Sickle cell trait vs. Sickle cell disease
Trait: heterozygous, generally asymptomatic, Disease: homozygous, chronic health problems
Vaso-occlusive crisis
Severe, abdominal pain (kidney, liver spleen infarction)
Acquired Hemolytic Anemia
Normal red cells that are unable to survive due to a hostile environment; Attacked and destroyed by antibodies and Destruction of red cells by mechanical trauma
Clotting Disorders
Disseminated intravascular Coagulation (DIC), Thrombotic Thrombocytopenic Purpura TTP –clots form in small blood vessels damaging RBC
Diagnostic Evaluation of Anemia
History and physical examination, Complete blood count to assess the degree of anemia, leukopenia, and thrombocytopenia, Blood smear to determine if normocytic, macrocytic, or hypochromic microcytic, Reticulocyte count to assess the rate of production of new red cells, lab tests, bone marrow study, and evaluation of blood loss
Secondary polycythemia
Common, Reduced arterial oxygen saturation leads to a compensatory increase in red blood cells (increased erythropoietin production)
Primary or polycythemia vera
Rare, Manifestation of diffuse marrow hyperplasia of unknown etiology (cause), an overproduction of red cells, white cells, and platelets; can evolve into granulocytic leukemia
Polycythemia Complications
Clot formation due to increased blood viscosity and platelet count
Polycythemia Treatment (both types)
Primary polycythemia: Treated with drugs that suppress marrow function
Secondary polycythemia: Periodic removal of excess blood
Secondary thrombocytopenic purpura
Damage to bone marrow from drugs or chemicals; Bone marrow infiltrated by leukemic cells or metastatic carcinoma
Primary/ Immune thrombocytopenic purpura (ITP)
Associated with platelet antibodies where the bone marrow produces platelets, but they are rapidly destroyed, chronic in adults (immune suppression for treatment)
Lymphatic System function
Provide immunologic defenses against foreign material via cell-mediated and humoral defense mechanisms and provides return of lost circulatory volume to vascular system
Lymph nodes
Bean-shaped structures consisting of a mass of lymphocytes supported by a meshwork of reticular fibers that contain scattered phagocytic cells
Where is lymphoid tissue
Present in thymus, tonsils, adenoids, lymphoid aggregates in intestinal mucosa, respiratory tract, and bone marrow
Thymus
Overlies base of the heart; large during infancy and childhood; undergoes atrophy in adolescence (essential in the prenatal development of the lymphoid system and in the formation of body’s immunologic defence mechanisms ( T cell development/ selection))
Spleen
Specialized to filter blood (Macrophages, antibodies, lymphocytes and sinusoids to detect and remove pathogens in blood)
Reasons for splenectomy
Traumatic injury: To prevent fatal hemorrhage
Blood diseases: Excessive destruction of blood cells in the spleen (hereditary hemolytic anemia)
Prevent chronic splenomegaly
Cancer – Leukemia, Lymphoma
Effects/risks of a splenectomy
Less-efficient elimination of bacteria (especially if blood-borne)
Impaired production of antibodies
Predisposed to systemic infections
Risk of increased platelet/RBC
Which infections are splenectomy patients at risk of?
Streptococcus pneumoniae, Haemophilus influenzae, and meningococcus infections
Treatment for Splenectomy
Vaccines and antibiotic prophylaxis
Infectious mononucleosis
Lymphatic System disease; usually caused by Epstein-Barr virus (EBV-B-cell 90%) or CMV – Tcell/macrophages (5-7%)
Risk: spleen may rupture during high-contact sports and in those with compromised immune systems (give rise to B cell lymphoma)
Enlarged LN cancers
Metastatic tumors: Breasts, lung, colon, other sites, Malignant lymphoma (Hodgkin lymphoma
and Non-Hodgkin lymphoma), and Lymphocytic leukemia
Leukemia
A neoplasm (Cancer) of hematopoietic tissue; Leukemic cells diffusely infiltrate the bone marrow and lymphoid tissues, spill over into the bloodstream, and infiltrate throughout various organs of the body
Aleukemic leukemia
Condition in which white cells are confined to the bone marrow such that their number in the peripheral blood is normal or decreased
Myelodysplasia (Preleukemia)
A disturbed growth and maturation of marrow cells; 3 types: Anemia (Reduced number of erythrocytes), Leukopenia (Reduced number of white cells), Thrombocytopenia (Reduced number of platelets)
Not all patients develop leukemia
Common types of hematopoietic cells that give rise to leukemia
Granulocytic, Lymphocytic, and Monocytic
CLL, CML, ALL, AML
chronic lymphocytic leukemia, chronic myelogenous leukemia, acute lymphocytic leukemia, and acute myeloid leukemia
Splenomegaly
Enlarged spleen
Hepatomegaly
Enlarged liver
Lymphadenopathy
Enlarged lymph nodes
Bone pain in Leukemia
Expansion of cells in bone marrow
Chronic leukemia
The evolution of disease proceeds at a relatively slow pace and often can be controlled
Acute leukemia
A rapidly progressive disease, more difficult to control
Diagnosis Leukemia
flowcytometry (phenotyping) bone marrow biopsy, Karyotyping (numbers, disease-specific risk genes – BCR/ABL fusion)
Lymphoma
When cancerous cells form solid tumors in LN; mostly diseased B-cells or some T-cells which disrupt immune function
Hodgkin Lymphoma
young adults, start in single LN and spreads to others and eventually other parts of the body. Usually detected early as a single or group of enlarged LN
Reed-Steinberg cells
(large atypical B-cells) that act as nucleus of tumor and secrete cytokines to attract other tumor cells
Non-Hodgkin
Older adults, variable in appearance an progression, often not detected until widespread dissemination has occurred
Treatment of Leukemia and Lymphoma + survival rate
Destruction of malignant cells by chemotherapy or radiation to produce remission (3 phases: Induction/Consolidation/Maintenance)
Other treatments:
- Hematopoietic Stem Cell Therapy (BMT, peripheral, cord blood): replaces malignant cells (must use immune suppression drugs)
50% 5 year survival rate if HLA match is found
