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80 Cards in this Set
- Front
- Back
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transferrin
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carries iron in plasma
is up-regulated during iron deficiency |
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ferritin
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major storage form of iron
is down-regulated during iron deficiency |
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major causes of iron loss (4)
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#1 = blood loss - stool, mentruation, ulcers
desquamation of iron-containing epithelial cells of skin and gut relative diet deficiency - infancy, adolescent, pregnant malabsorption - celiac disease, gastrectomy |
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Where is iron absorbed?
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Duodenum
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Hepcidin
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protein produced by hepatocytes when intracellular iron increases
decreases gut iron absorption by binding to membrane ferroportin leading to its internalization and degradation |
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Iron deficient RBC morphology
4 stages |
Stage 1 - normochoromic, normocytic
Stage 2 - normochromic, microcytic Stage 3 - HYPOCHROMIC, MICROCYTIC Stage 4 - hypochromic, microcytic, poikilocytic |
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Clinical signs of iron deficiency (4)
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mucosal atrophy of tongue and stomach
alopecia pica GI malabsorption |
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Causes of microcytic anemia (5)
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Iron loss
Lead poisoning Myelodysplasia Syndrome Sideroblastic Anemia Thalessemia |
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Hemochromatosis
cause diagnosis technique tx |
autosomal recessive disorder causing increased GI iron absorption
variable penetrance in homozygotes dx - liver biopsy, genetic analysis tx - phlebotomy |
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General cause of megaloblastic anemia
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impaired DNA synthesis
increased fragility of cells therefore increased hemolysis all dividing cells in body effected increase in ineffective hematopoesis |
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Bone marrow findings in megaloblastic anemia
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Looks like it is hyperplastic
(but really cells are stuck in S phase) increase in megaloblastic erythroid and granulocytic precursors megakaryocytes have increased # nuclei nuclear:cytoplasmic dissociation |
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Peripheral blood findings in megaloblastic anemia
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Pancytopenia w/reticulocytopenia
Variation in RBC size (anisocytosis) & shape (poikilocytosis) Macro-ovalocytes Hypersegmentation of polys If HCT <20 - see teardrop cells & nucleated RBCs |
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Clinical features of megaloblastic anemia
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Slowly developing anemia
Pallor, fatigue, SOB GLOSSITIS GI complaints Weight loss B12 specific - paresthesias, problems walking, atrophy of tongue papillae |
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Lab findings in megaloblastic anemia
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MCV >110
pancytopenia increased LDH, bilirubin, serum iron decreased plasma haptoglobin |
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Pernicious Anemia
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inadequate intrinsic factor secretion
therefore decreased B12 absorption leads to megaloblastic anemia gastric atrophy often precedes anemia fatal if untx |
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Causes of B12 deficiency
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Inadequate intake (rare b/c v. large liver stores) possible in vegans
Malabsorption - lack of IF, bacterial overgrowth, fish tapeworm, ileal disease or resection, post-gastrectomy, chronic use of PPI deficiency of trancobalamin II |
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Dx of B12 deficiency
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Serum cobalamin assay
High methylmalonic acid and homocysteine in serum Low levels of methionine (common to folate deficiency too) Schilling's test |
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Causes of folate deficiency
(6) |
decrease in diet
increased requirement (pregnancy, preemie, malignancy, inflammatory disease, increased BM turnover) malabsorption (would have to be severe) drug-induced - anticonvulsants, barbituates excess losses - dialysis, CHF alcohol, liver diease |
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Diagnosing folate deficiency
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Low RBC folate - most accurate
Serum folate increased serum homocysteine |
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Hereditary Spherocytosis
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Autosomal dominant
Extravascular hemolysis due to defects in membrane proteins ankyrin and/or spectrin (majority) |
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Manifestations of Hereditary Spherocytosis
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anemia, splenomegaly, jaundice, gallstones (b/c increased bilirubin turnover)
severely affected kids - growth retardation, delayed sexual development, extramedullary hematopoesis, skin ulcers, thalessemia facies (bones of skull elongate) |
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Complications of Hereditary Spherocytosis (3)
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1. hemolytic crisis - typically due to viral illness
2. aplastic crisis - after viral-mediated BM suppression (usually Parvovirus B19). Can lead to CHF & death 3. Megaloblastic crisis - pts w/increased demands |
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Diagnosis of Hereditary Spherocytosis
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increased MCHC (mean corpuscular Hb conc.)
Positive osmotic fragility test - RBCs are incubated in increasingly hypotonic solutions and spherocyted lyse sooner |
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Pyruvate Kinase Deficiency
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autosomal recessive
imp't in Embden-Meyerhof pathway In last step of glycolytic pathway - converts phosphenolpyruvate to pyruvate RBC can't make ATP & causes hemolytic anemia - variable but worsened by stress, infection |
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G6PD Deficiency
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causes hemolytic anemia
encoded on X chromosome imp't in Hexose Monophosphate shunt - cell protection from oxidative injury b/c G6PD catalyzes 1st step in generation of NADPH (reduces glutathione) which maintains HB in soluble, reduced form |
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Heinz body
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insoluble Hb precipitates seen in G6PD Deficiency
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Pyrimidine 5' nucleotidase deficiency
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causes hemolytic anemia
RNA is degraded into purines & pyrimidines as RBC matures 5' nucleotidase converts the nucleotides -> nucleosides In normal RBC nucleoside can diffuse out of cell but when deficient in Pyrimidine 5' nucleotidase, NUCLEOTIDES ACCUMULATE & are toxic to RBC |
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methemoglobin
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derivative of Hb where Iron is in FERRIC state (3+)
blood is a dark brown color 20-30% will cause cyanosis |
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Inherited methemoglobin - deficiency in what enzyme?
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deficiency of cytochrome b5 reductase in RBCs -
enzyme which transfers e- to MetHb to reduce it |
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Inherited methemoglobin Tx
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methylene blue acts as e- donor (reducing agent)
Fe 3+ -> Fe 2+ |
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Warm Antibody Type Immune-Mediated Hemolytic Anemia
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most common type of autoimmune H.A. Assoc. w/ SLE, CLL, some drugs e.g. methyldopa
IgG - usually reactive vs. Rh antigen 2 mechanisms of destruction: Ab coats RBC & RBC is phagocytosed in spleen OR RBC is heavily coated w/Ab & complement is (+) |
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Clinical manifestations of WAIHA
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jaundice
splenomegaly SOB Fatigue |
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Lab findings in WAIHA
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decreased haptoglobin, Hb, Hct
Increased LDH, indirect bilirubin +ve Coombs test |
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Tx for WAIHA (5)
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Transfusion
Prednisone Azathioprine, cyclophosphamide IVIg Splenectomy |
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Cold Antibody Type Immune-Mediated Hemolytic Anemia
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IgM = "cold agglutinins"
react w/surface RBC glycoproteins I/i and (+) complement May follow infection by mycoplasma, EBV |
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Clinical manifestations of CAIHA
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at low temps Abs agglutinate RBCs
Usually in perpheral areas - fingers, ears, toes, nose Usually no splenomegaly b/c hemolysis is mostly intravascular |
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Tx of CAIHA
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Prevention and keeping patient warm
Steroids and splenectomy are not helpful |
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Causes of Drug-related Hemolytic Anemia (3)
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1. Antibody Induction: assoc. most often w/methydopa. Induces AutoAbs vs. RBCs. +ve direct Coombs test. presentation similar to WAIHA
2. Immune Complex Formation: Ab forms vs. drug in plasma. Complex deposits on RBC and (+) complement. cephalosporins, quinine, quinidine 3. Drug absorption: drug binds firmly to RBC. Ab forms vs RBC-drug complex. Usually IgG rx to penicillin |
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Paroxysmal Cold Hemoglobinuria + Donath Landsteiner Antibody
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IgG antibody reacts w/RBC in COLD
Clinical signs: in cold pt. develops leg, abd. cramps, rigors, dark urine Assoc. w/ congenital or tertiary syphillis Young ppl & kids get it post-viral infection Usually self-limited if avoid cold May respond to prednisone |
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Immune Thrombocytopenic Purpura
(ITP) overview |
autoreactive Abs vs. platelet glycoproteins.
more common in females in kids - usually post-infection and self-limited in adults - may be assoc. w/ SLE, RA, HIV, Hepatitis, H. pylori |
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Immune Thrombocytopenic Purpura
(ITP) Clinical Presentation |
varies from asymptomatic -> acute onset petichiae & severe disease
usually affects women in 20's & 30's widespread bruising & bleeding - epistaxis, gingival bleeding, hematuria, menorrhagia |
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Peripheral Smear & Bone Marrow findings in
Immune Thrombocytopenic Purpura |
increased platelet size, decrease in number
*exclude pseudothrombocytopenia (in vitro artifact) BM: reactive megakaryocyte hyperplasia |
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Diagnosis of Immune Thrombocytopenic Purpura
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Clinical Diagnosis and one of exclusion
antiplatelet Ab assay has high false negative result |
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Tx of Immune Thrombocytopenic Purpura
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steroids
can relapse splenectomy if unable to maintain high enough count (>30K) |
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Genotypes for sickle cell disease (3)
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1. Homozygous for HbS - Sickle cell anemia. Most clinically severe.
2. HbSC disease - compound heterzygosity for HbS and HbC genes 3. HbS-thalassemia - compound heterzygosity for HbS and one of the thalassemia genes |
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Hydroxyurea
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Tx for sickle cell disease
Increases HbF |
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Diagnosis of Sickle Cell Disease
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50% or more HbS in blood
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Hematological Features of Sickle Cell Trait
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Normal PCV, MCV & MCH, reticulocyte count
Normal blood film 60% HbA, 40% HbS Normal levels of HbA2 and HbF |
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Membrane damage caused by sickle Hb (3)
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increased adherence to endothelial cells
increased tastiness to macrophages tendency to lose water and cations |
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Some Complications of Sickle Cell Disease
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Acute painful episode-most patients, frequent
Acute chest syndrome-sometimes lethal Aplastic crisis: due to Parvovirus B19 infection Stroke-10% of children Salmonella Osteomyelitis Splenic infarction, sequestration-anemia, infection Increased risk of encapsulated organism infection |
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Initial Presentation of Patient w/Sickle Cell Disease
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First few years of life
Can have any of the following: Painful swelling of hands & feet Chest pain w/hypoxia & lung infiltrate Acute bouts of abdominal or bone pain |
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Tx Sickle Cell Disease
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Acute and chronic pain management
General medical care Hydroxyurea Transfusion Stem cell transplantation |
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Thalassemia definition
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Thalassemias are due to markedly reduced or absence of globin chain production from mutated globin gene, such as in alpha- or beta-thalassemias.
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A Clinical Classification of Beta Thalassemia - trait
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Beta thalassemia trait (heterozygous beta thalassemia; thalassemia minor)
Beta-Thalassemia Trait microcytosis, hypochromia, +/- mild anemia elevated level of HbA2 (>3.5%) |
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A Clinical Classification of Beta Thalassemia - Major
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Beta thalassemia major (Homozygous or compound heterozygous beta thalassemia; Cooley's anemia)
transfusion-dependent microcytic anemia very high HbF (approaching 100%) |
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Beta Thalassemia Treatment
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Transfusion
Iron chelation |
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What is the change in globin gene expression during development and what does it mean for the manifestation of B thalessemia?
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Gamma-globin genes are expressed in utero
Near birth there is a down-regulation of gamma expression and an upregulation of B-globin gene expression The switch is complete by 6 months therefore B-chain mutations aren't manifested until 6 months after birth (is true for sickle cell too) |
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Beta Thalassemia Lab Diagnosis-
Carrier (3) |
Microcytosis (low MCV)
Normal serum ferritin Elevated HbA2 |
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Major cause of death in Beta Thalassemia
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cardiac disease due to iron overload
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alpha-thalassemia phenotypes:
silent carrier trait |
silent carrier: mutation involving a single alpha gene. clinically are well, normal Hb, normal/borderline low MCV
trait: mutation involving 2 genes. clinically are well. normal/borderline low Hb, microcytosis (resembles iron-deficient anemia) |
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Hb H disease
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there is only one normal alpha globin gene
excess B-globin chains form tetramers = HbH moderate anemia, marked microcytosis otherwise well other may need tranfusions |
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Hb Barts hydrops fetalis
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fetus lacks all alpha globin genes
Hb Barts = gamma chain tetramers only make zeta2 gamma2 Hb fetuses usually die in 2nd semester or hours after birth Mother is at high risk of complications (preeclampsia, HTN, hemorrhage) |
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Lab diagnosis of alpha-thalassemias
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microcytosis (MCV <80)
Normal serum ferritin (excludes iron deficiency) |
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Burkitt's Lymphoma: What is the
translocation function of affected gene |
t(8;14)
c-myc activation c-Myc is a transcription factor that controls cell proliferation |
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Low grade follicular lymphomas: What is the
translocation function of affected gene |
t(14;18)
fuses Ig to bcl-2, an anti-apoptosis gene |
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mantle cell lymphoma
What is the: translocation function of affected gene |
t(11;14)
fuses Ig-to cyclin D1 Cell cycle progression is controlled by cyclins and cyclin-dependent kinases |
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Presenting symptoms and signs of lymphoma
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Fatigue and malaise
“B” symptoms of fever, weight loss, sweats Enlarged lymph nodes that are typically rubbery, non-tender, and chronic Abdominal or mediastinal mass Splenomegaly (from cancer spread to organ) Elevated WBC |
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Hodgkin’s Disease: epidemiology
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Bi-modal age incidence
Major peak in 20’s Rising incidence again in elderly Increased incidence in northern climes Higher incidence in upper class socioeconomic groups, small families, first-born children |
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What virus is Hodgkin’s Disease linked to?
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EBV
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Non-Hodgkin's Lymphoma Classification:
Low? Intermediate? High? |
Low grade: Small cleaved cell lymphomas, nodular lymphomas
Intermediate grade: Large cell lymphomas, diffuse lymphomas (small, large, or mixed) High grade: Immunoblastic, Lymphoblastic (lymphoma form of ALL), Burkitt’s |
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Do Hodgkin's Lymphoma cells express CD 19 and CD 20?
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No, they do not express CD 19 or 20 despite being B-cell in origin
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More common form of Hodgkin's Lymphoma found in women?
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Nodular sclerosis.
It is also the most common type according to Rye classification. |
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Most common type of leukemia?
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CLL
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Name of CLL when only found in lymph nodes?
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Small lymphocytic lymphoma
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CD expression of CLL (4 impt ones)
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CD5+
CD19+ CD23+ (-ve in mantle cell) CD10- (+ve in follicular lymphoma) |
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CLL - disease of young, middle age or old?
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Median age at diagnosis is 70
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Diagnosis of chronic lymphocytic leukemia
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Lymphocytosis
Bone marrow involvement of > 30% lymphocytes. <55% atypical/immature lymphoid cells in peripheral blood. Clonal expansion of abnormal B lymphocytes. Low density of surface Ig (IgM or IgD) with clonal expression of either k or l chains. B cell surface antigens (CD19, CD20, CD23) CD5 surface expression |
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Does early tx in CLL improve survival?
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No
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CLL Prognostic Factors (4)
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Bad Prognosis:
Rai stage of high risk Fast lymphocyte doubling time Unmutated VH region/low amts ZAP-70 (ie no somatic hypermutation) cytogenetics (FISH) - 17p deletion (loss of p53), 11q deletion, trisomy 12 **deletion of 13q14 has a good prognosis |
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Leading causes of death in CLL
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Bacterial Repiratory Tract Infections - pneumonia, bronchitis
Hypogammaglobulinemia correlates w/ increased # infections |
