Flashcards de JESS
What is the definition of immunodeficiency?
A state in which the immune system’s ability to fight infectious disease is compromised or entirely absent.
What is LAD-1?
Leukocyte adhesion deficiency type 1, characterized by increased bacterial infections, absence of pus, and impaired wound healing.
What are common manifestations of LAD-1?
- Increased frequency of bacterial infections
- Absence of pus
- Delayed separation of the umbilical cord
- Omphalitis
- Destructive periodontitis
- Recurrent infections with S. aureus
What is the pathophysiology of LAD-1?
An autosomal recessive mutation in the integrin LFA-1 on phagocytes affecting chemotaxis and adhesion.
What laboratory findings are associated with LAD-1?
- Leukocytosis (+11,000)
- Absence of CD18, CD11a, CD11B, CD11c
What is the main therapy for LAD-1?
Bone marrow transplant.
What is CGD?
Chronic granulomatous disease, caused by defects in NADPH oxidase leading to impaired ROS generation.
What are the types of CGD?
- X-linked: mutation in CYBB gene
- Autosomal recessive: mutation in p47phox
What are common infections seen in CGD?
- Pneumonia
- Liver abscess
- Skin infections
- Osteomyelitis
What is the Dihydrorhodamine assay used for?
To assess NADPH oxidase activity in CGD.
What characterizes X-linked/Burton agammaglobulinemia?
A mutation in the BTK enzyme leading to a block in B-cell maturation.
What are common infections associated with X-linked/Burton agammaglobulinemia?
- Recurrent upper and lower respiratory tract infections
- Infections caused by pyogenic encapsulated bacteria
What is the hallmark diagnosis for X-linked/Burton agammaglobulinemia?
Absence of B cells with normal T cells.
What is Hyper IgM syndrome?
A class-switching defect characterized by an inability of B cells to switch from IgM to other immunoglobulin classes.
What are the types of Hyper IgM syndrome?
- Type 1: X-linked syndrome
- Type 2: Autosomal recessive
What are the laboratory findings in Hyper IgM syndrome?
- Normal or high IgM
- Low IgG
- Low IgA and IgE
- Absent germinal centers on lymph node biopsy
What is Common Variable Immunodeficiency?
A defect in B-cell differentiation leading to reduced immunoglobulin production.
What are common manifestations of Common Variable Immunodeficiency?
- Recurrent respiratory infections
- Poor response to immunization
- Low immunoglobulin levels of all types
What characterizes Severe Combined Immunodeficiency (SCID)?
Near complete absence of circulating autologous T cells and impaired B cell and NK function.
What are the different types of SCID based on T cell status?
- T-B+NK-
- T-B+NK+
- T-B-NK+
What are typical symptoms of SCID?
- Severe persistent infections
- Oral thrush
- Chronic diarrhea
- Failure to thrive
What is the treatment for SCID?
Bone marrow transplant and avoidance of live vaccines.
What is Systemic Lupus Erythematosus (SLE)?
An autoimmune disease characterized by the production of autoantibodies and immune complex formation.
What are common manifestations of SLE?
- Fever
- Arthralgia
- Rash (malar, discoid)
- Renal failure
What is the main laboratory test for diagnosing SLE?
Presence of antinuclear antibodies (ANAs).
What is the pathophysiology of Rheumatoid Arthritis?
Inflammation of the synovium leading to synovial hypertrophy and destruction of cartilage and bone.
What are common symptoms of Rheumatoid Arthritis?
- Symmetrical joint pain and swelling
- Morning stiffness
- Bone erosions
What is the significance of HLA-DR4 in Rheumatoid Arthritis?
It is a genetic predisposition factor associated with the disease.
What are common lab findings in Iron Deficiency Anemia?
- Low ferritin
- Low serum iron
- High transferrin
- MCV less than 80
What is Sideroblastic Anemia?
Anemia caused by defective protoporphyrin synthesis leading to iron trapping in mitochondria.
What is Thalassemia?
A hereditary hemoglobin disorder characterized by mutations in the alpha or beta globin chains.
What are common symptoms of Beta thalassemia?
Chipmunk facies, jaundice, swollen abdomen, frequent infections, liver disease
Symptoms typically appear between 3-6 months of age.
What laboratory findings are associated with Alpha thalassemia?
Low Hgb, MCV, MCHC
Golf ball-like cells may also be observed.
What are the laboratory findings for Beta thalassemia?
Low Hgb, low MCV, high RDW, high serum iron, ferritin, transferrin, LOW HbA, high HbF and HbA2
DNA sequencing can confirm the diagnosis.
What is hereditary spherocytosis?
An inherited disorder caused by intrinsic defects in the red cell skeleton that makes red cells spheroid, less deformable and vulnerable to splenic sequestration and destruction.
What genetic defects are associated with hereditary spherocytosis?
Defects in ankyrin gene, band 3, spectrin, and band 2
It is inherited in an autosomal dominant pattern.
What are the key features of G6PD deficiency?
X-linked inherited disorder causing hemolysis with certain foods, may be protective against malaria, causes neonatal hyperbilirubinemia, chronic hemolytic anemia
Heinz bodies and bite cells may be observed.
What is pyruvate kinase deficiency?
An autosomal recessive disorder leading to hemolytic anemia due to deficiency of pyruvate kinase.
What are common symptoms of autoimmune hemolytic anemia?
Fatigue, pale skin, dyspnea, tachycardia, jaundice, splenomegaly
Characterized by a positive direct antiglobulin test.
What is the main cause of sickle cell anemia?
Autosomal recessive pattern with a point mutation on the beta globin gene, replacing glutamic acid with valine.
What triggers sickling in sickle cell anemia?
Deoxygenation, cold, dehydration, insomnia, alcohol, stressful situations, overexertion, hormonal changes.
What is aplastic anemia?
Normochromic normocytic anemia due to deficiency of all blood cell types from bone marrow damage.
What are the laboratory findings in anemia of chronic disorders?
Normochromic, normocytic or mildly hypochromic, with high hepcidin, less serum iron, low transferrin, high ferritin, low TIBC.
What are the symptoms of vitamin B12 deficiency?
Glositis, weakness, paresthesia, confusion, dementia
Acid methylmalonic acid can accumulate in neurons.
What is the significance of hypersegmented neutrophils?
Indicates megaloblastic anemia, often related to vitamin B12 or folate deficiency.
What is the role of TPO in platelet production?
TPO is the regulatory hormone of platelet production, synthesized in the liver.
What are the steps involved in hemostasis?
Vasoconstriction, platelet plug formation, coagulation, fibrinolysis.
What is immune thrombocytopenia purpura (ITP)?
A type of thrombocytopenia involving the formation of autoantibodies against platelets.
What are the manifestations of thrombotic thrombocytopenic purpura?
Petechial hemorrhage, neurological issues, low platelet count, schistocytes
It is characterized by a pentad of symptoms.
True or False: Cold agglutinin disease is primarily associated with warm autoimmune hemolytic anemia.
False
Cold agglutinins are associated with cold autoimmune hemolytic anemia.
What laboratory tests are normal in immune thrombocytopenia?
PT, INR, TT, PTT normal.
What is the peak age for vitamin B12 deficiency?
60 years.
Fill in the blank: Fibrinolysis is the conversion of plasminogen into _______.
plasmin.
What is the most common cause of uremic hemolytic syndrome?
Infection with Shiga-toxin producing E. coli, particularly the strain 0157:H7.
This bacteria produces toxins that damage the lining of blood vessels.
List three clinical manifestations of uremic hemolytic syndrome.
- Hemolytic anemia
- Thrombocytopenia
- Acute kidney injury
What is thrombocytopenia?
A condition characterized by a low platelet count.
What are the common causes of drug-induced thrombocytopenia?
- Quinine
- Quinidine
- Heparin
What is the major factor responsible for thrombocytopenia in hypersplenism?
Splenomegaly.
True or False: In thrombocytopenia due to hypersplenism, the platelet lifespan is usually normal.
True.
Define Thrombasthenia (Glanzmann’s disease).
An autosomal recessive disease with mutations in the genes coding GIIb/IIIa, leading to failure of platelet aggregation and prolonged bleeding times.
What is Bernard-Soulier syndrome?
An autosomal recessive syndrome with defects in platelet adhesion due to a mutation in the GP1b gene.
What is the definition of Hemophilia A?
A congenital disorder caused by VIII deficiency, resulting from an X-linked mutation.
What laboratory finding is increased in Hemophilia A?
aPTT (activated partial thromboplastin time).
What is the most common hereditary clotting factor deficiency?
Hemophilia A.
What is the defining mutation in von Willebrand Disease?
A mutation on the gene vWF at chromosome 12.
What are the manifestations of vitamin K deficiency?
- Increased risk of bleeding
- GI bleeding
- Bruising
What is disseminated intravascular coagulation (DIC)?
A condition characterized by systemic activation of the clotting cascade leading to thromboembolic state and consumption of coagulation factors and platelets.
List three risk factors for myelodysplastic syndrome.
- Tobacco smoking
- Ionizing radiation
- Exposure to benzene, herbicides, pesticides
What is acute myeloid leukemia (AML)?
A cancer that originates in the bone marrow, causing rapid proliferation of abnormal myeloid cells.
What are common cytogenetic abnormalities associated with acute myeloid leukemia?
- Translocation (8;21)
- Inv (16)
- t(15;17)
What is the most common form of acute leukemia in adults?
Acute myeloid leukemia (AML).
What is the typical age range for acute lymphoblastic leukemia (ALL)?
3-17 years.
What is a common translocation associated with a poor prognosis in ALL?
t(9;22), also known as the Philadelphia chromosome.
True or False: Chronic lymphocytic leukemia (CLL) typically presents with lymphocytosis and lymphadenopathy.
True.
What are the common genetic abnormalities associated with CLL?
- Deletion of 13q
- Deletion of 11q
- Deletion of 17p
What is Hodgkin lymphoma characterized by?
The presence of Reed-Sternberg cells, which are CD15 and CD30 positive.
What are B symptoms in Hodgkin lymphoma?
- Fever
- Diaphoresis
- Weight loss
What is the term for the discrete enlargement of superficial lymph nodes?
Lymphadenopathy
Often associated with various conditions including infections and malignancies.
What are B symptoms in lymphoma?
Fever, diaphoresis, weight loss
These symptoms are commonly seen in aggressive lymphomas.
What is the significance of RS cells?
They are characteristic of Hodgkin’s lymphoma
RS cells are also known as Reed-Sternberg cells.
What type of lymphocytes are primarily involved in Non-Hodgkin’s lymphoma?
B cells (85%) and T/NK cells (15%)
Non-Hodgkin’s lymphoma has a worse prognosis compared to Hodgkin’s lymphoma.
What mutation is commonly associated with mantle cell lymphoma?
CCND1 (cyclin D1) t(11;14)
This mutation leads to increased cell proliferation.
What genetic abnormality is associated with chronic myeloid leukemia?
t(9;22) leading to BCR-ABL1 fusion
This results in a hybrid gene that causes uncontrolled cell growth.
What is the main clinical feature of Burkitt’s lymphoma?
Jaw mass, associated with EBV and HIV
It is characterized as aggressive and high grade.
What is the function of the JAK2 V617F mutation in polycythemia vera?
Causes intrinsic overactivity in the bone marrow
This leads to an increase in red blood cell production.
What is the typical platelet count in essential thrombocythemia?
Greater than or equal to 450,000
This condition is characterized by thrombocytosis.
What are common symptoms of primary myelofibrosis?
Anemia, massive splenomegaly, weight loss
It often leads to abdominal discomfort and pain.
What is the primary cell type involved in chronic myeloid leukemia?
Mature granulocytes
This results from uncontrolled proliferation of mature myelocytes.
Fill in the blank: The presence of the Philadelphia chromosome is a characteristic finding in _______.
chronic myeloid leukemia
It is a result of the BCR-ABL1 fusion.
True or False: Follicular lymphoma is considered aggressive.
False
Follicular lymphoma is classified as indolent.
What diagnostic tool is ideal for staging lymphomas?
PET-CT with FDG
This imaging study helps in assessing the extent of the disease.
What is a common feature of acute presentations in aggressive lymphomas?
Rapidly growing mass
This is particularly noted in DLBCL and Burkitt lymphoma.
What mutation is commonly found in essential thrombocythemia?
JAK2 V617F mutation
Other mutations can include MPL and CALR.
What are the common manifestations of polycythemia vera?
Headaches, dyspnea, blurred vision
Symptoms are often related to increased blood viscosity.
What is the most advanced stage of chronic myeloid leukemia?
Blast cell phase
This phase can progress to acute myeloid leukemia (AML).
What is the main difference between primary and secondary polycythemia?
Primary is intrinsic overactivity, secondary is EPO-driven
Secondary causes can include smoking or high altitude.
What does the term ‘spent phase’ refer to in polycythemia vera?
An advanced stage characterized by bone marrow fibrosis
It may also lead to myelofibrosis.
