Chapter 11 - Hematopoetic and Lymphoid System Flashcards
Microcytic
small red blood cells
decreased mean corpuscular volume
Macrocytic
large blood cells
increased mean corpuscular volume
Hypochromic
pale red cells
decreased mean corpuscular hemoglobin
Poikilocytosis
oddly shaped red cells
Anisocytosis
mixture of red cell sizes
Target cells
bulls-eye red cells
What are the different screening tests for Anemia?
hemoglobin, RBC indices (MCV, MCH), Reticulocyte Count (Marker of bone marrow response to low hemoglobin), Serum Ferritin (Adequacy of bone marrow iron stores), Peripheral Blood Smear Morphology (Clues to anemia causation)
Hemolytic anemias
A. Mechanical injury and microangiopathy
Mechanical injury - artificial heart valves
Microangiopathy - vessels narrowed by fibrin, DIC, or uremia
B. Immune mediated processes
Idiopathic, SLE, Rh arthritis, Lymphomas and chronic lymphocytic leukemias
C. Infection
Malaria
D. Hemoglobinopathies
Sickle cell anemia (AR), Thalassemia (AD)
Anemias of Impaired red cell production and decreased proliferation and differentiation
A. Anemia of suppression of bone marrow cells - aplastic anemia
B. Anemia of diminished erythropoiesis (nutritional deficiency) - iron deficiency anemia, vitamin B12 deficiency anemia, folic acid deficiency anemia
C. Anemia of ineffective erythropoiesis - anemias of chronic disease
D. Pernicious anemia - autoimmune anemia
Hemolytic Anemia
Increased rate of red cell destruction
May be caused by mechanical trauma to red cells, autoimmune destruction of red cells, genetic abnormality resulting in abnormal hemoglobin structure, and genetic abnormality in red cell biochemistry
Mechanical & Microangiopathic Hemolytic anemia
Mechanical - artificial heart valves of mechanical type
Microangiopathic hemolytic anemia - RBCs squeezed through abnormally narrowed vessels filled with fibrin, seen in disseminated intravascular coagulation and hemolytic uremic syndrome induced by E.coli infection
Immune Mediated Hemolytic Anemias
Red cells are opsonized w/ antibody usually IgG which makes them targets for removal by the spleen which recognizes them as abnormal, 60% idiopathic and remainder are associated with another disease
Infection Related Hemolytic Anemias
Malaria - Blackwater Fever: a complication of malaria in which RBCs burst in the blood stream (hemolysis) releasing hemoglobin directly into the vessels and into urine, frequently leading to kidney failure, cerebral malaria is most severe form
Hemoglobinopathies
A group of hereditary disorders characterized by the presence of a structurally abnormal hemoglobin
Most common inherited genetic disorder worldwide
Result in decreased red cell survival and often acute hemolysis under certain biochemical and physiologic stress
Sickle Cell Anemia
Cause by the mutation in the beta-globulin chain
Single point mutation (missense mutation) in beta-hemoglobin gene that converts a GAG codon into a GUG, which encodes amino acid valine rather than glutamic acid, polymerization when deoxygenated
AR inheritance
Heterozygotes have about 40% HbS and 60% HbA
Removed from circulation by spleen reducing life span from 120 to 20 days
may cause widespread microvascular obstructions resulting in hypoxic tissue injury
Oral manifestations of Sickle Cell Anemia
Orofacial and dental pain with absence of dental pathology, Pallor of the oral mucosa, Delayed eruption of teeth may be seen, Radiographic findings: step ladder trabecular pattern in the mandible is noted in 70% of patients
Thalassemia
Heterogeneous group of genetic disorders of Hb synthesis characterized by a lack of or decreased synthesis of globin chains
Reduced beta chains in hemoglobin or reduced alpha chains
Microcytic and hypochromic, Red cell hemolysis
Thalassemia Major (Cooley’s Anemia)
Beta thalassemia result from either complete absence of beta chain globin synthesis or markedly reduced synthesis, thus abnormality is quantitative rather than qualitative as in sickle cell
AD inheritance
Unpaired alpha chains form insoluble precipitates which damage red cell membranes
Causes severe hemolytic anemia
Bone growth abnormalities due to expansion of the hematopoietic marrow leads to dental malocclusion
“Hair on end appearance, Chipmunk face”
Thalassemia Minor
Heterozygous state, mild microcytic hypochromic anemia
Normal life expectancy
No bone growth abnormalities
Resembles iron deficiency anemia; serum iron studies normal
Oral manifestations of Thalassemia Major
spiky shaped and short roots, taurodontism, attenuated lamina dura, enlarged bone marrow spaces, small maxillary sinuses, Class II malocclusion, higher caries, no inc in gingivitis or periodontitis, salivary concentrations of phosphorous and IgA reduced may result in inc caries
Aplastic Anemia
suppression of multipotential bone marrow stem cells resulting in pancytopenia
Suppression of hematopoiesis mediated by cytotoxic T lymphocytes, these cells produce inhibitory cytokines such as gamma interferon and tumor necrosis factor
Oral manifestations: hemorrhage, candidiasis, viral infection
Iron Deficiency Anemia
initially, normochromic, normocytic until depletion, then microcytic, hypochromic
Iron deficiency anemia is the most common nutritional anemia
Values, Low hemoglobin, hematocrit, MCV, MCH, serum ferritin, and serum iron level
Iron Deficiency Anemia causes:
Chronic Blood Loss: women (menstruation and post menopause), men (colonic carcinoma), both: gastric ulcers (NSAIDS)
Dietary: infants (breast fed only beyond 6 mo), develops at 1 yr
Vitamin B12 Deficiency (Megaloblastic Anemia)
B12 & folate are necessary for DNA synthesis
Abnormally large immature red cell precursor in bone marrow called megaloblasts
Uncorrected deficiency leads to demyelination of nerves
Symmetrical numbness of hands and feet, as well as cognitive impairment in older individuals
Treatment: frequent parenteral injections of Vitamin B12
Folate (Folic acid) Deficiency
Diminished dietary intake, increased demand (pregnancy), metabolic problems (alcoholism), drug-induced (methotrexate), Deficiency does not cause demyelination as does B12 deficiency
Anemia of Chronic Disease
Mimics iron deficiency anemia except that bone marrow iron is normal or inc and serum ferritin levels are normal or increased
Associated with Chronic microbial infections, chronic immune disorders, defect in the utilization of recycled iron
Pernicious Anemia
Malabsorption of Vitamin B12, Autoimmune gastritis
prevents binding of B12 to intrinsic factor
Leukopenia (Decrease in white cells)
Neutropenia (dec in # of neutrophils)
Agranulocytosis (severe dec in granulocytes
Pathogenesis: decreased granulocyte production, increased granulocyte destruction, immune mediated injury, in overwhelming bacterial, fungal or rickettsial infections, inc peripheral utilization
Oral Health - dec in neutrophil counts, associated w/ painful mouth ulcerations
Lymphopenia (dec in # of lymphocytes)
Leukocytosis
Inc. in number of white blood cells
Neutrophilic: acute bacterial infections
Eosinophilic: allergic disorders like asthma, hay fever, allergic skin diseases
Monocytosis: chronic infections (TB)
Lymphocytosis: chronic immunologic stimulation, viral infections
Lymphocytosis
infectious mononucleosis
acute, self-limiting disease, chiefly of adolescents and young adults, Caused by ***Epstein Barr Virus (EBV)
Symptoms: fever, sore throat, cervical lymphadenopathy
Spleen is enlarged and susceptible to rupture, liver affected often causing a subclinical hepatitis
Non-Hodgkin’s Lymphoma
neoplastic proliferation of lymphoid cells, usually arising in lymph nodes (65%) - remainder in parenchymal organs or soft tissue sites
Oral manifestations: intra oral mass, periapical pathology and mimics toothache, non healing ulceration w/ ill-defined irregular margins
B cell Neoplasm: Burkitt Lymphoma
endemic (Africa) and sporadic
African form presents w/ massive involvement of maxilla and mandible
Caused by Epstein Barr Virus infection
Extranodal Marginal Zone Lymphoma
Formerly MALT lymphoma, arises in association w/ mucosal sites
Favorable prognosis
May occur in oral cavity, conjuctiva, breast, gut, and salivary gland
arising in Hashimoto’s throiditis, Sjogren syndrome, H. pylori gastritis
Mycosis Fungoides
Cutaneous (skin) lymphoma of neoplastic CD4+ T-cells, may eventually involve lymph nodes
May become generalized erythrodermic process “Sezary syndrome”
Hodgkin Lymphoma
B-cell lineage neoplastic disorder, begins in a single node or node group
“Reed-Sternberg”
Classification: Nodular sclerosis (most common), lymphocyte rich, mixed cellularity, lymphocyte depletion, lymphocyte predominance, nodular type
Oral manifestations: treated w/ radiation causing dry mouth if submandibular and sublingual glands
Acute Myeloid Leukemia (AML)
predominance of immature cells (myeloblasts), median age is about 50 years, most common acute leukemia in adults
Acute Lymphocytic Leukemia (ALL)
Primarily disease of children, Peak incidence 4 years of age
pre-B cell origin
2-10 yrs w/ pre-B ALL have best prognosis (curable)
mature B-cell phenotype or T-cell type have less favorable prognosis
Adults are much less favorable
Chronic Myeloid Leukemia
**Thrombocytosis (inc platelets) is common
about 90% of CML patients have the Philadelphia chromosome (Ph1), a 9:22 translocation
Gives rise to bcr-abl fusion gene which encodes ro an abnormal enzyme, bcl-abl tyrosine kinase
Slow progression, bone marrow transplant effecting
Chronic Lymphocytic Leukemia
Most indolent of all leukemias, affects over 50 yrs
B-cell neoplasm
hypogammaglobulinemia (low immunoglobulin levels) is common
Autoimmune hemolytic anemia
accumulation of long-lived, nonfunctional B lymphocytes that infiltrate the bone marrow, blood, lymph nodes, spleen and liver
Chronic Leukemia Oral manifestations
in contrast to acute leukemia, oral changes in chronic leukemia is uncommon
Polycythemia (Rubra) Vera
An acquired hematopoietic stem cell disorder
overproduction of red blood cells, white blood cells, and platelets
JAK2 V617F mutations
JAK2 mutation renders cells hypersensititive to erythropoietin
Symptoms: Pruritus, Hemorrhagic and thrombotic complications
Oral Manifestations: Red-purple (erythematous) oral mucosa
Multiple Myeloma
Malignant clonal proliferation of plasma cells in bone marrow
associated w/ multifocal “punched out” lytic bone lesions
Cells produce abnormal immunoglobulins -> “Bence-Jones” protein
Bone pain, fractures, renal failure, immunosuppression
Dental: poor healing, jawbone involvement, bleeding tendency, infections, pain and paresthesia
Plasmacytoma
Single lesions of “multiple myeloma”
May occur in jaw bones or oral soft tissues rarely
may remain indolent for years, most become more like usual case of multiple myeloma eventually (5-10 yrs)
Langerhans cell histiocytosis (Histiocytosis X)
Clonal, neoplastic proliferation of dendritic antigen-presenting cells Langerhans cells (dendritic mononuclear cells found in epidermis, mucosa, lymph nodes, and bone marrow) BRAF mutations have been identified in 40-60% of cases
Single organ involvement (bone or skin)
Multi-organ involvement (no organ dysfunction or organ dysfunction (low-risk/high-risk)
Hand-Schuller-Christain disease
Letterer-Siwe disease
> 50% of cases seen in young patients
Skull, ribs, vertebrae, and mandible are common sites
Jaws are affected in 10-20% of cases
Radiographically, sharply punched-out radiolucencies w/out a corticated rim
Disseminated Intravascular Coagulation (Consumptive Coagulopathy)
Overactivation of the coagulation cascade leads to formation of thrombi throughout the microcirculation
Intro of tissue thromboplastins during trauma or obstetrical complications and widespread injury to endothelial cells from bacterial endotoxins during gram-negative species are triggered by
Paradoxical - results from overactivity of the coagulation cascade rather than a primary failure to clot
Thrombocytopenia
Platelet counts in range of 20,000/uL or less
Small vessel bleeding is characteristic producing petechiae, purpura and ecchymoses
Lack of production (bone marrow suppression) Decreased survival (autoimmune: ITP, viral: infectious mono [EBV], Consumptive: Disseminated intravascular coagulation)
Idiopathic Thrombocytopenic Purpura (ITP)
Autoimmune: may be isolated or may precede such diseases such as SLE)
Most common in females from 20-40 yrs
Hemophilia - Factor VIII (Hemophilia A)
Classic, accounts for 80% of hemophilias, X-linked recessive trait, 30% are new mutations and do not have fam history
“Royal Disease”
Factor IX Deficiency (Hemophilia B)
Christmas Disease, X-linked recessive, clinically resembles Factor VIII def, much less common and less severe
Von Willebrand Disease
Usually mild symptoms, underdiagnosed
Most common inherited bleeding disorder
Either AD or AR, complete lack produces no levels of Factor VIII and is similar to severe factor VIII deficiency
Massive Splenomegaly due to “Infiltrative Disease”
Chronic myeloproliferative disorders, chronic myeloid leukemia, chronic lymphocytic leukemia, hairy cell leukemia, lymphoma
Massive Splenomegaly due to Circulatory disorders
Portal hypertension from liver cirrhosis, congestive heart failure
Hypersplenism
excessive removal of 1+ of formed elements of the blood (Thrombocytopenia, neutropenia, anemia)
Primary hypersplenism: no existing splenic disease
Secondary hypersplenism: secondary to a disease w/ splenic involvement such as chronic leukemia
