Hema-Immuno Pathology Flashcards
1
Q
Neutropenia can be caused by
A
- inadequate or ineffective granulopoiesis or
- increased destruction or sequestration of neutrophils in the periphery
2
Q
Neutropenia can be caused by
A
- inadequate or ineffective granulopoiesis or
- increased destruction or sequestration of neutrophils in the periphery
3
Q
Accelerated destruction/ Sequestration occurs in
A
immune-mediated injury, splenomegaly and increased peripheral utilization
4
Q
The most common cause of agranulocytosis is
A
Drug toxicity (i.e. chemo drugs, anticonvulsants and antipsychotic meds). These drugs cause a generalized suppression of hematopoiesis such that production of RBC and platelets is also affected
5
Q
In acute infection (Leukocytosis) there is a
A
Rapid increase in the egress of mature granulocytes from the bone marrow pool, an alteration that may be mediated through the effects of tumor necrosis factor (TNF) and interleukin-1 (IL-1)
6
Q
Mechanisms and Cause of Leukocytosis
Increase Marrow Production
A
Chronic Infection or inflammation (Growth factor-dependent)
Paraneoplastic (Hodgkin lymphoma: GF-Depedent)
Myelproliferative neoplasm (CML GF-Independent)
7
Q
Mechanisms and Cause of Leukocytosis
Increasae Release from Marrow Stores
A
Acute inflammation (infection)
Chronic Inflammation
8
Q
Mechanisms and Causes of Leukocytosis
Decrease Margination and Decrease Extravasation Into Tissue
A
Decrease Margination
- Exercise
- Catecholamines
Decrease Extravasation Into Tissue
-Glucorticoids
9
Q
Neutrophilic Leukocytosis
A
Acute bacterial Infection - Pyogenic organisms; Sterile inflammation ex- Tissue Necrosis (MI and Burns)
10
Q
Eosinophilic Leukocytosis (Eosinophilia)
A
Allergic disorders
-Asthma
-Hay fever
-Parasitic infestations
-Drug reactions
Malignancies
-Hodgkin and NHL
Autoimmune disorders
-Pemphigus
-Dermatitis
-Herpetiformis
Vasculitides and Atheroembolic Disease
11
Q
Basophilic Leukocytosis (Basophilia)
A
Rare- Myeloproliferative neoplasm
12
Q
Monocytosis
A
Chronic Infections
-TB
-Bacterial endocarditis
-Rickettsiosis
Malaria
Autoimmune disorders
-SLE
-IBD
13
Q
Lymphocytosis
A
Accompanies monocytosis and Disorders associated with chronic immunologic stimulation
14
Q
Lymphocytosis
A
Accompanies monocytosis and Disorders associated with chronic immunologic stimulation
15
Q
Different patterns of morphologic change are seen often within the same lymph node. These changes include
A
-follicular hyperplasia, paracortical hyperplasia and sinus histiocytosis
16
Q
Lymphoid neoplasms
A
B-cell, T-cell, and NK-cell origin
17
Q
Lymphoid neoplasms
A
B-cell, T-cell, and NK-cell origin
18
Q
Myeloid neoplasms
A
acute myeloid leukemias, myelodysplastic syndromes, myeloproliferative neoplasms
19
Q
Histiocytoses
A
Langerhans cell histiocytoses
20
Q
HTLV-1 is associated with
A
adult T-cell leukemia/lymphoma
21
Q
HTLV-1 is associated with
A
adult T-cell leukemia/lymphoma
22
Q
EBV is found in a subset of
A
Burkitt lymphoma, Hodgkin lymphoma (HL), many B-cell lymphomas and rare NK-cell lymphomas
23
Q
HHV-8 is associated with
A
unusual B-cell lymphoma.
24
Q
The incidence of AML is
A
increased 1.3- to 2-fold in smokers, presumably because of exposure to carcinogens, such as benzene, in tobacco smoke
25
Acute Lymphoblasitc leukemia/lymphomas (ALLs)
are neoplasms composed of immature B (pre-B) or T (pre-T) cells, which are referred to as lymphoblasts
most common cancer of children. About 85% are B-ALLs manifest as childhood acute leukemias. The less common T-ALLs tend to present in adolescent males as thymic lymphomas
26
In leukemic presentations
the marrow is hypercellular and packed with lymphoblasts, which replace normal marrow elements
27
The most common leukemia of adults in western world
Chronic lymphocytic leukemia/ Small lymphocytic lymphoma
28
Is the most common form of indolent NHL in the United States, trailing only diffuse large B-cell lymphoma in frequency among lymphomas.
14:18 translocation
Follicular Lymphoma
29
is the most common form of NHL. The median patient age is about 60 years, but DLBCL also occurs in young adults and children
The common features are a relatively large cell size and diffuse pattern of growth
Diffuse large B-Cell lymphoma
30
associated with translocations of the MYC gene on chromosome 8 that lead to increased MYC protein levels. The MYC translocation partner is usually the IGH locus [t(8;14)].
8:14
Burkitt Lymphoma
31
Burkit lymphoma characteristic pattern commonly seen
Starry sky pattern
32
uncommon lymphoid neoplasm and as the name implies, the tumor cells closely resemble the normal mantle zone B cells that surround germinal centers
11;14
Mantle Cell Lymphoma
33
The extranodal tumors were initially recognized at mucosal sites and are often referred to as mucosa-associated lymphoid tumors (or MALTomas).
They often arise within tissues involved by chronic inflammatory disorders, they remain localized, and they may regress if the inciting agent is eradicated
Marginal Zone Lymphoma
34
The extranodal tumors were initially recognized at mucosal sites and are often referred to as mucosa-associated lymphoid tumors (or MALTomas).
They often arise within tissues involved by chronic inflammatory disorders, they remain localized, and they may regress if the inciting agent is eradicated
Marginal Zone Lymphoma
35
associated in more than 90% of cases with activating point mutations in the serine/threonine kinase BRAF.
Hair cell leukemia
36
associated in more than 90% of cases with activating point mutations in the serine/threonine kinase BRAF.
Hair cell leukemia
37
No morphologic feature is pathognomonic, but certain findings are characteristic. These tumors efface lymph nodes diffusely and are typically composed of a pleomorphic mixture of variably sized malignant T cells
wastebasket diagnosis
Peripheral T-Cell lymphoma
38
This uncommon entity is defined by the presence of rearrangements in the ALK gene on chromosome 2p23
Containing horseshoeshaped nuclei and voluminous cytoplasm (hallmark cells).
Anaplastic large-cell lymphoma
39
This neoplasm of CD4+ T cells is observed only in adults infected by HTLV-1.
The appearance of the tumor cells varies, but cells with multilobated nuclei ("cloverleaf" or "flower" cells) are frequently observed
Adult T-Cell leukemia/lymphoma
40
Multiple Myeloma
A plasma cell neoplasm commonly associated with lytic bone lesions, hypercalcemia, renal failure, and acquired immune abnormalities.
Factors produced by neoplastic plasma cells mediate bone destruction, the major pathologic feature of multiple myeloma. One important factor appears to be myeloma-derived MIP1a (also known as CCL3
destructive plasma cell tumors (plasmacytomas) involving the axial skeleton. The bones most commonly affected (in descending order of frequency) are the vertebral column, ribs, skull, pelvis, femur, clavicle, and scapula.
Rouleaux formation
41
It is a B-cell neoplasm of older adults that usually presents in the sixth or seventh decade of life.
Most commonly, the plasma cell component secretes monoclonal IgM, often in amounts sufficient to cause a hyperviscosity syndrome Known as Waldenström macroglobulinemia
Lymphoplasmacytic lymphoma
42
Arises in a single node or chain of nodes and spreads first to anatomically contiguous lymphoid tissues.
Morphologically, the distinctive feature of Hodgkin lymphoma is the presence of neoplastic giant cells called Reed-Sternberg cells
Hodgkin lymphoma
43
Hodgkin lymphoma pathogenesis
Activation of the transcription factor NF-B is a common event in classic Hodgkin lymphoma and turns on genes that are believed to promote the growth and survival of Reed-Stemberg cells.
44
HL vs NHL
HL
- Single axial group of nodes often localized
-Orderly spready by contiguity
NHL
-Multiple peripheral nodes
-Waldeyer ring and mesenteric nodes commonly involved
-Extranodal presentation common
45
is a tumor of hematopoietic progenitors caused by acquired oncogenic mutations that impede differentiation, leading to the accumulation of immature myeloid blasts in the marrow.
The replacement of the marrow with blasts produces marrow failure and complications related to anemia, thrombocytopenia, and neutropenia
8;21
Acute Myeloid Leukemia
46
a distinctive subtype of AML, the t(15;17) creates a fusion gene encoding a chimeric protein consisting of the retinoic acid receptor-a (RARa) and a portion of a protein called PML
15;17
Acute promyelocytic leukemia
47
Distinguished from other myeloproliferative neoplasms by the presence of a chimeric BCR-ABL gene derived from portions of the BCR gene on chromosome 22 and the ABL gene on chromosome 9.
BCR-ABL is created by a reciprocal (9;22) (q34;q11) translocation (Philadelphia chromosome (Ph]).
9;22
Chronic Myeloid Leukemia
48
Bone Marrow findings in pating with CML
The marrow is hypercellular because of massively increased numbers of maturing precursors. The blood reveals granulocytic a leukocytosis, often exceeding 100,000 cells/mm3
49
characterized increased Marrow production of red by cells, granulocytes, and platelets (panmyelosis), but it is the increase in red cells (polycythemia) that is responsible for most of the clinical symptoms.
the transformed progenitor cells have markedly decreased requirements for erythropoietin and other hematopoietic growth factors due to activating mutations in the tyrosine kinase JAK2.
Polycythemia Vera
50
The most common mutation is an activating valine-to-glutamate substitution at residue 600 in BRAF.
Have abundant, often vacuolated cytoplasm containing presence of Bibeck granules
Langerhans Cell Histiocytosis
51
Certain changes are seen in hemolytic anemia regardless of cause or type.
• Increased numbers of erythroid precursors (normoblasts) in the marrow.
• Prominent reticulocytosis in the peripheral blood.
• Accumulation of the iron-containing pigment hemosiderin (hemosiderosis).
• Extramedullary hematopoiesis can appear in the liver, spleen, and lymph nodes.
• Formation of pigment gallstones
52
Intravascular Hemolysis of red cells may be caused by
mechanical injury, complement fixation, intracellular parasites (e.g., falciparum malaria), or exogenous toxic factors.
53
is an inherited disorder caused by intrinsic defects in the red cell membrane skeleton that render red cells spheroid, less deformable, and vulnerable to splenic sequestration and destruction.
caused by diverse mutations that lead to an insufficiency of membrane skeletal components (ankyrin, band 3, spectrin, or band 4.2). The life span of affected red cells is decreased on average to 10 to 20 days.
Hereditary Spherocytosis
54
Abnormalities in the hexose monophosphate shunt or glutathione metabolism resulting from deficient or impaired enzyme function reduce the ability of red cells to protect themselves against oxidative injuries and lead to hemolysis
episodic hemolysis is caused by exposures that generate oxidant stress.
G6PD Deficiency
55
common hereditary hemoglobinopathy caused by a point mutation in β- globin that promotes the polymerization of deoxygenated hemoglobin, leading to red cell distortion, hemolytic anemia, microvascular obstruction, and ischemic tissue damage.
missense mutation that leads to the replacement of a charged glutamate residue with a hydrophobic valine residue.
Sickle Cell Disease
56
genetically heterogeneous a disorder caused by germline mutations that decrease the synthesis of either α-globin or βglobin, leading to anemia, tissue hypoxia, and red cell hemolysis.
Thalassemia
57
The anemia manifests 6 to 9 months after birth as hemoglobin synthesis switches from HbF to HbA. The red cells may completely lack HbA (βO/ β0 genotype) or contain small amounts (β+/ β+ or β0/β+ genotypes).
B-Thalassemia major
58
inherited deletions that result in reduced or absent synthesis of αglobin chains. Normal individuals have four αglobin genes, and the severity of α-thalassemia depends on how many a-globin genes are affected.
a-Thalassemia
59
deletion of two α-globin genes from a single chromosome (α/α -/-) or the deletion of one αglobin gene from each of the two chromosomes (α/-α/-).
a-Thalassemia Trait
60
deletion of three α-globin genes
Hemoglobin H disease (HbH)
61
The most severe form of a-thalassemia, is caused by deletion of all four α-globin genes.
Hydrops Fetalis
62
A disease that result from acquired mutations in the phosphatidylinositol glycan complementation group A gene (PIGA), an enzyme that is essential for the synthesis of certain membrane-associated complement regulatory proteins.
Paroxysmal Nocturnal Hemoglobinuria
63
The diagnosis of immunohemolytic anemia requires the detection of antibodies and/or complement on red cells from the patient. This is done using
Direct and Indirect Coombs antiglobulin tests
64
impairment of DNA synthesis that leads to ineffective hematopoiesis and distinctive morphologic changes, including abnormally large erythroid precursors and red cells.
Megaloblastic Anemia
65
Megaloblastic Anemia 2 principal substypes
pernicious anemia (the major form of vitamin B12 deficiency anemia) and folate deficiency anemia (B9)
66
specific form of megaloblastic anemia caused by an autoimmune gastritis that impairs the production of intrinsic factor, which is required for vitamin B12 uptake from the gut.
Pernicious anemia
67
3 Major causes of folic acid deficiency are
1. decreased intake
2. increased requirements
3. impaired utilization
68
most common nutritional disorder in the world and results in signs and symptoms that are related to inadequate hemoglobin synthesis
Iron Deficiency Anemia
69
The Major sites of Storage iron are
liver and mononuclear phagocytes. It is transported in plasma by iron-binding protein called a transferrin, which is synthesized in the liver.
70
Syndrome of chronic primary hematopoietic failure and attendant pancytopenia (anemia, thrombocytopenia) neutropenia, and
The most common circumstances associated with aplastic anemia follow exposure to chemicals and drugs. Some of the associated agents (including many cancer chemotherapy drugs and the organic solvent benzene) cause marrow suppression that is dose related and reversible.
Aplastic Anemia
71
Excessive bleeding can result from
1. increased fragility of vessels
2. platelet deficiency or dysfunction
3. derangement coagulation, alone or in combination.
72
This test assesses the extrinsic and common coagulation pathways
Prothrombin Time (PT)
73
This test assesses the intrinsic and common clotting pathways.
Partial Thromboplastim Time (aPTT)
74
Autoantibody-mediated destruction of platelets. It can occur in the setting of a variety of predisposing conditions and exposures (secondary) or in the absence of any known risk factors (primary or idiopathic).
Autoantibodies most often directed against platelet membrane glycoproteins IIb-Illa or Ib-IX in the plasma and bound to the platelet surface in about 80% of patient
Chronic Immune Thrombocytopenic Purpura
75
This condition is also caused by autoantibodies to platelets. Symptoms appear abruptly, often 1 to 2 weeks after a self-limited viral illness, which appears to trigger the development of autoantibodies through uncertain mechanisms.
Self-limited, usually resolving spontaneously within 6 months
Acute Immune Thrombocytopenic Purpura
76
Drugs associated in Drug Induced Thrombocytopenia
The drugs most commonly implicated are quinine, quinidine, and vancomycin, all of which induce drug-dependent antibody binding to platelet glycoproteins
Drugs can induce thrombocytopenia through direct effects on platelets and secondary to immunologically mediated platelet destruction.
77
TTP is caused by a deficiency in a plasma enzyme called
ADAMTS13, also designated "vWF metalloprotease
78
HUS is associated with normal levels of ADAMTS13 and can be
1. defects of adhesion
2. defects of aggregation
3. disorders of platelet secretion (release reaction)
79
adhesion defect caused by an inherited deficiency of the platelet membrane glycoprotein complex Ib-IX.
Bernard-Soulier Syndrome
80
exemplifies bleeding due to defective platelet aggregation associated with dysfunction of glycoprotein IIb- Illa.
Glanzmann thromboasthenia
81
most common hereditary disease associated with life-threatening bleeding, is caused by mutations in factor VIII. Patients with hemophilia A have a prolonged PTT and a normal PT.
Hemophilia A
82
severe factor IX deficiency. Like hemophilia A, it is inherited as an X-linked recessive trait. The PTT is prolonged and the PT is normal.
Hemophilia B
83
severe factor IX deficiency. Like hemophilia A, it is inherited as an X-linked recessive trait. The PTT is prolonged and the PT is normal.
Hemophilia B
84
Average Lifespan of RBC
120 Days
85
Average Lifespan of RBC
120 Days
86
Small Round RBC Cells without central pallor
Spherocytes
87
Small Round RBC Cells without central pallor
Spherocytes
88
RBC apperance in G6PD
Bite cells
89
RBC apperance in G6PD
Bite cells
90
Deletion of 4 a-globulin chains
Hydrops fetalis
91
Regulate iron absorption in GUT
Hepcidine
92
Regulate iron absorption in GUT
Hepcidine
93
Most common cause of Agranulocytosis
Drugs
94
Most common cause of Agranulocytosis
Drugs
95
Most common cancer in children
Acute Lymphoblastic Leukemia
