Hematological and Immunological Dysfunction Flashcards
anemia
condition in which the number of red blood cells or the hemoglobin concentration is reduced below normal values for gender and age. This diminishes the oxygen carrying capacity of the blood, causing reduction in oxygen available to tissues
most common hematological disorder of infancy and childhood
not a disease itself but manifestation of underlying pathological process
anemia classifications
classified according to etiology or physiology, manifested by erythrocyte or hemoglobin depletion, morphology, the characteristic changes in RBC size, shape, or colour
etiology or physiology: decreased RBC production, increased RBC loss, increased RBC destruction
morphology: cell size (anisocytosis) - normocytes 0 normal, microcytes - small, macrocytes - large; cell shape (poikilocytosis) - spherocytes (globular), drepanocytes (sickle cell), numerous other irregularities; colour - normochromic (sufficient or normal hemoglobin per RBC), hypochromic (reduce hemoglobin per RBC), hyperchromic (increased hemoglobin per RBC)
iron deficiency anemia
oral iron should be given in two divided doses between meals, when the presence of free hydrochloric acid is greatest since more iron is absorbed in an acidic environment. iron supplement should not be taken with milk. adequate dosage of iron turns stool tarry green.
sickle cell anemia
SCA is one of a group of disease collectively term hemoglobinopathies, in which adult hemoglobin A is completely or partially replaced by sickle cell hemoglobin S. for as long as the fetus has hemoglobin F (fetus hemoglobin) the cells do not start sickling - therefore, neonate asymptomatic for SCA until fetal Hgb replaced by sickle Hgb
3 most common forms of sickle cell disease
sickle cell anemia - HgbSS; homozygous form of the disease
sickle cell-c disease - heterozygous form of SCD, includes both HgbS and HgbC
sickle thalassemia disease - combination of sickle cell trait and beta thalassemia trait (SB-thal), B+ refers to the ability to still produce some normal hemoglobin; B0 indicates no ability to produce normal hemoglobin
sickle cell anemia: pathophysiology
clinical features result of obstruction caused by sickled RBC, vascular inflammation, and increased RBC destruction. meshing of sickled RBC caused vaso-occlusion, resulting in tissue hypoxia, tissue ischemia and infraction (cellular death), effect of sickling occurs in this order; statis with enlargement, infraction with ischemia and repeated destruction, replacement with fibrous tissue (scarring)
Crises in Sickle Cell Anemia
vaso-occlusive crisis - ischemia causing mild to severe pain that last from minutes to days
sequestration crisis - pooling of large amount of blood; usually in spleen or liver; that causes a decreased blood volume and shock
aplastic crisis - diminished RBC production caused by viral infection
hyperhemolytic crisis - accelerated rate of RBC destruction characterized by anemia, jaundice, and reticulocytosis
SCA severity indicators
Manifestations that appear in the first two years of life can be predictors of disease severity. These include elevated WBC count, painful episodes, and severe anemia
Beta Thalassemia (cooley Anemia)
deficiencies in the rate of production of specific globin chains in the hemoglobin. occurs in four formation:
two heterozygous forms - thalassemia minor, an asymptomatic silent carrier; thalassemia trait, produces mild microcytic anemia
thalassemia intermedia, manifested as splenomegaly and moderate to severe anemia
homozygous form, thalassemia major (cooleys anemia) which results in severe anemia that leads to cardiac failure and death in early childhood without transfusions
beta thalassemia pathophysiology
partial or complete deficiency in the synthesis of the beta chain of the hemoglobin molecule. consequently, there is a compensatory increase in alpha chain production and gamma chain remains active, resulting in defective hemoglobin formation. when the defective hemoglobin disintegrates it damaged RBC, resulting in anemia.
beta thalassemia transfusion therapy
advantages of therapy include improved physical and psychological wellbeing bc of ability to participate in normal activities, decreased cardiomegaly and hepatosplenomegaly, fewer bone changes, normal or near normal growth and development until puberty, and fewer infection
complication of frequent transfusion is iron overload due to the body having no effective method of disposing of excess iron and so it stores it back into body tissues (hemosiderosis) - chelation therapy given to counter iron overload
aplastic anemia
bone marrow failure condition in which the formed elements of the blood are simultaneously depressed. peripheral blood smear indicates pancytopenia, which is the triad of anemia - reduced RBC - leukopenia - reduce WBC - and thrombocytopenia - reduce platelets. Hypoplastic anemia is characterized by profound depression of RBC, but minor depression of WBC and platelets. commonly found in congenital disorder Fanconi amenia
Tx for aplastic anemia
therapy directed at restoring bone marrow function and takes two approaches; immunosuppressive therapy to remove the presumed immunological functions that prolong aplasia or replacement of the bon marrow through transplant. HSCT is also considered
hemophilia
group of bleeding disorders in which there is a deficiency in one of the factors necessary for coagulation of blood (vascular influence, platelet role, or clotting factors). two most common forms of the disorder are factor VIII deficiency, Hemophilia A or Classic hemophilia, and Factor IX deficiency (hemophilia B or Christmas disease). von Willebrand disease is another hereditary bleeding disorder characterized by the deficiency, abnormality, or absence of the von Willebrand factor protein and a deficiency of factor VIII.
Hemophilia A pathophysiology
deficiency in Factor VIII needed for formation of thromboplastins in phase 1 of blood coagulation. Individuals with hemophilia A have vascular influence and platelet, but lack clotting factors, therefore, they may bleed for longer periods, but not at a faster rate. most frequent type of internal bleeding with hemarthrosis - bleeding into joint space (knees, elbows, ankles, etc).
therapy for hemophilia A
primary therapy is replacement of missing clotting factor VIII. products available are factor viii concentrate from pooled plasma or genetically engineered recombinant, reconstituted with sterile water before use. a synthetic form of vasopressin, DDAVP, increases plasma factor VIII activity and is tx of choice in mild hemophilia A and certain types of vWD - not useful in severe hemophilia A, severe vWD, or any hemophilia B.
idiopathic (autoimmune) thrombocytopenia purpura
acquired hemorrhagic disorder characterized by thrombocytopenia - excessive destruction of platelets - purpura - discolouration caused by petechiae beneath the skin - normal bone marrow with normal or increased number of immature platelets and eosinophils. disease occurs as either acute, self limiting course or a chronic condition (greater than 6 month duration). dx through clinical manifestation such as easy bruising, bleeding from mucous membranes, and internal hemorrhage
disseminated intravascular coagulation (DIC)
diffuse fibrin deposition in the microvasculature, consumption of the coagulation factors, and endogenous generation of thrombin and plasmin. DIC is a secondary coagulation disorder that occurs as a complication of pathological processes. DIC occurs when the first stage of coagulation is abnormally stimulated
2 phases of DIC
first: clotting mechanism is triggered in the circulation, thrombin is generated at an amount greater than the body can neutralize it. then there is rapid conversion of fibrinogen to fibrin, with aggregation and destruction of platelets. if the fibrin becomes widespread across blood vessels, obstruction and necrosis of tissue occurs.
second: fibrinolytic mechanism is activated, causing destruction of clotting factors. This leads to uncontrollable hemorrhage in vital organs
epistaxis
nosebleeding.
leukemia
cancer of the blood forming tissues. most common childhood cancer. broad term given to a group of malignant diseases of the bone marrow and lymphatic system. two forms of leukemia, acute lymphoid leukemia (ALL) and acute non-lymphoid (myelogenous) leukemia (AML)
3 main consequences of leukemia
anemia from decreased RBC, infection from neutropenia (low production of neutrophils - a type of WBC), and bleeding from decreased platelet production
four phases of chemotherapy in leukemia
induction therapy, achieves complete remission or less than 5% leukemic cells in the bone marrow; CNS prophylactic therapy, prevents leukemic cells from invading CNS; intensification (consolidation) therapy, eradicated residual leukemia cells - followed by delayed intensification, which prevents emergence of resistant leukemia clones; maintenance therapy, to maintain remission period
ALL; initial prognostic factors
initial WBC count, child’s age at time of diagnosis, type of cell involved, sex of child, and karyotype analysis. children with normal or low WBC and non-T, non-B ALL and are CALLA positive have much better prognosis
leukemia: frequency of infection
most susceptible at time of diagnosis and relapse when the leukemic process has replaced normal leukocytes; during immunosuppressive therapy; after prolonged antibiotic therapy.
leukemia drug toxicity symptoms (expected)
nausea and vomiting anorexia mucosal ulcers neuropathy (dysfunction or damage to nerves) hemorrhagic cystitis (damage/inflammation of the inner lining of the bladder) alopecia steroid effects mood changes
hodgkins disease
neoplastic disease that originates in the lymphoid structure and primarily involves the lymphoid. Predictably metastasizes to non-nodal or extralymphatic sites, like spleen, liver, bone marrow, etc. four histological types; lymphocytic predominance, nodular sclerosis, mixed cellularity, and lymphocytic depletion. reed-sternberg cells sign of disease (cell have owl eye appearance)
Ann Arbor staging of hodgkins disease
based on number of sites of lymph node involvement, presence of extranodal disease, and history of symptoms. Classified as A for asymptomatic or B for symptoms of fever, drenching night sweats, and unexplained weight loss over 6 months
non-hodgkins lymphoma
difference from hodgkins; disease is diffuse rather than nodular, cell type is undifferentiated or poorly differentiated, dissemination occurs early, more often, and rapidly, mediastinal involvement and invasion of meninges is common. 3 classifications of NHL are; lymphoblastic, Burkitt or non-Burkitt, or large cell. tx; similar to leukemia with induction, consolidation, and maintenance therapy
HIV and AIDS
mother to child transmission or adolescent risky behaviour. Retrovirus that is transmitted by lymphocytes and monocytes. Found in blood, semen, vaginal secretions, and breast milk. Horizontal transmission is through sex or exposure to blood or body fluids, vertical transmission is from mother to baby. take over and depletion of CD4 lymphocyte cell
severe combined immunodeficiency disease
defect characterized by the absence of both humoral and cell mediated immunity. tx: HSCT
Wiskott-Aldrich Sydnrome (WAS)
X-linked recessive disorder characterized by thrombocytopenia, eczema, and immunodeficiency of selective functions of B and T lymphocytes. defective gene called WAS protein. tx: counteracting bleeding with platelet transfusion, IV gamma-globulin to provide passive immunity, prophylactics antibiotics, and aggressive local therapy for eczema. only cure is HSCT
blood transfusion therapy
take vitals, including BP before admin of blood to establish baseline data. then every 15min for 1 hr while blood infusing and on completion of transfusion. check id of recipient and donors blood group and type. admin first 50ml or 20% of volume (whichever is smaller) slowly and stay with child. admin normal saline on piggyback or have normal saline available. admin blood through appropriate filter to eliminate articles in blood and prevent precipitation of formed elements. use blood within 30min of arrival, if not return to blood bank, do not store in regular fridge. infuse ordered blood within 4 hrs. if order will exceed this time, blood should be divided into appropriately sized quantities by blood bank. if rx of any type, stop transfusion, take vital, maintain patent IV line with normal saline and new tubing and notify provider
Hematopoietic stem cell transplant (HSCT)
used to establish healthy hemopoiesis in both malignant and nonmalignant disease. Immune system repressed to prevent rejection of transplanted marrow, the stem cell harvested from the bone marrow, peripheral blood, or umbilical vein of the placenta are given to pt via IV transfusion. pt in hospital 3-6wks
graft versus host disease (GVHD)
risk of HSCT. while pt immune system repressed and will not reject donor marrow, donor marrow may have antigens that pt does not, which then attack body cells. more closely match HLA, less likely for GVHD
different types of HSCT
allogeneic HSCT: matching a histocompatible donor with recipient. low availability of matched marrow donors.
umbilical cord SCT: cord blood fairly immunodeficient at birth, allowing for partially matched unrelated cord blood transplants to be successful, with low risk of GVHD
autologous HSCT: patients own marrow that is collected from disease free tissue, frozen, and sometimes treated to remove malignant cells.
peripheral SCT: type of autologous transplant, differs in way stem cell collected. CSF given to stimulate production of stem cells. after WBC count is high enough, stem cell collected via machine. machine filters out peripheral stem cell from whole blood, returns remainder of blood cell and plasma to child. Stem cell frozen until child ready for transplant
apheresis
