Hematology and Oncology - Pathology (1) Flashcards
1
Q
Associated pathologies of these pathologic RBC forms
- Acanthocyte
- Basophilic stippling
- Bite cell
- Elliptocyte
- Macro-ovalocyte
- Ringed sideroblast
A
- Acanthocyte (spur cell) [A]
- Liver disease, abetalipoproteinemia (states of cholesterol dysregulation).
- Acantho = spiny.
-
Basophilic stippling [B]
- Anemia of Chronic Disease, alcohol abuse, Lead poisoning, Thalassemias.
- Basically, ACi_D_ alcohol is LeThal.
- Bite cell [C}
- G6PD deficiency.
- Elliptocyte [D]
- Hereditary elliptocytosis.
- Macro-ovalocyte [E]
- Megaloblastic anemia (also hypersegmented PMNs), marrow failure.
- Ringed sideroblast [F]
- Sideroblastic anemia.
- Excess iron in mitochondria = pathologic.
2
Q
Associated pathologies of these pathologic RBC forms
- Schistocyte
- Sickle cell
- Spherocyte
- Teardrop cell
- Target cell
A
- Schistocyte (helmet cell) [G]
- DIC, TTP/HUS, traumatic hemolysis (i.e., mechanical heart valve prosthesis).
- Sickle cell [H]
- Sickle cell anemia.
- Spherocyte [I]
- Hereditary spherocytosis, autoimmune hemolysis.
-
Teardrop cell [J]
- Bone marrow infiltration (e.g., myelofibrosis).
- RBC “sheds a tear” because it’s been forced out of its home in the bone marrow.
-
Target cell [K]
- HbC disease, Asplenia, Liver disease, Thalassemia.
- “HALT,” said the hunter to his target.
3
Q
Heinz bodies
- Process
- Associated pathology
A
- Process
- Oxidation of hemoglobin sulfhydryl groups –> denatured hemoglobin precipitation and phagocytic damage to RBC membrane –> bite cells.
- Visualized with special stains such as crystal violet.
- Associated pathology
- RBC pathology
- Seen in G6PD deficiency
- Heinz body–like inclusions seen in α-thalassemia.
4
Q
Howell-Jolly bodies
- Process
- Associated pathology
A
- Process
- Basophilic nuclear remnants found in RBCs.
- Howell-Jolly bodies are normally removed from RBCs by splenic macrophages.
- Associated pathology
- RBC pathology
- Seen in patients with functional hyposplenia or asplenia.
5
Q
Anemias
- Normocytic
A
- Normocytic (MCV = 80-100 fL)
- Nonhemolytic (reticulocyte count normal or decreased)
-
ACD
- May first present as a normocytic anemia and then progress to a microcytic anemia.
- Aplastic anemia
- Iron deficiency (early)
- Chronic kidney disease
-
ACD
- Hemolytic (reticulocyte count increased)
- Intrinsic
- Sickle cell anemia
- HbC defect
- RBC membrane defect: hereditary spherocytosis
- RBC enzyme deficiency: G6PD, pyruvate kinase
- Paroxysmal nocturnal hemoglobinuria
- Extrinsic
- Autoimmune
- Infections
- Microangiopathic
- Macroangiopathic
- Intrinsic
- Normally, you AAIC with SHa_RRP_ AIMM
- Nonhemolytic (reticulocyte count normal or decreased)
6
Q
Anemias
- Microcytic
- Macrocytic
A
- Microcytic (MCV < 80 fL)
- Thalassemias
-
ACD
- May first present as a normocytic anemia and then progress to a microcytic anemia.
-
Iron deficiency (late)
- May first present as a normocytic anemia and then progress to a microcytic anemia.
- Lead poisoning
-
Sideroblastic anemia
- Copper deficiency can cause a microcytic sideroblastic anemia.
- Small TAILS
- Macrocytic (MCV > 100 fL)
- Megalobalstic
- Folate deficiency
- Orotic aciduria
- B12 deficiency
- Non-megaloblastic
- Liver disease
- Alcoholism
- Reticulocytosis
- Big FOB LAR
- Megalobalstic
7
Q
Iron deficiency
- Type of condition
- Description
- Findings
A
- Type of condition
- Microcytic, hypochromic (MCV < 80 fL) anemia
- Description
- Decreased iron due to chronic bleeding (GI loss, menorrhagia), malnutrition/absorption disorders or increased demand (e.g., pregnancy) –> decreased final step in heme synthesis.
- Findings
- Decreased iron, increased TIBC, decreased ferritin.
- Fatigue, conjunctival pallor [A].
- Microcytosis and hypochromia [B].
- May manifest as Plummer-Vinson syndrome (triad of iron deficiency anemia, esophageal webs, and atrophic glossitis).
8
Q
α-thalassemia
- Type of condition
- Description
- Defect
- cis
- trans
- Findings
- 4 allele deletion
- 3 allele deletion
- 1-2 allele deletion
A
- Type of condition
- Microcytic, hypochromic (MCV < 80 fL) anemia
- Description
- Defect: α-globin gene deletions –> decreased α-globin synthesis.
- cis deletion prevalent in Asian populations
- trans deletion prevalent in African populations.
- Findings
- 4 allele deletion:
- No α-globin.
- Excess γ-globin forms γ4 (Hb Barts).
- Incompatible with life (causes hydrops fetalis).
- 3 allele deletion:
- HbH disease.
- Very little α-globin.
- Excess β-globin forms β4 (HbH).
- 1–2 allele deletion:
- No clinically significant anemia.
- 4 allele deletion:
9
Q
β-thalassemia
- Type of condition
- Description
- Findings
- β-thalassemia minor
- β-thalassemia major
- HbS/β-thalassemia heterozygote
A
- Type of condition
- Microcytic, hypochromic (MCV < 80 fL) anemia
- Description
- Point mutations in splice sites and promoter sequences –> decreased β-globin synthesis.
- Prevalent in Mediterranean populations.
- Findings
-
β-thalassemia minor (heterozygote):
- β chain is underproduced.
- Usually asymptomatic.
- Diagnosis confirmed by increased HbA2 (> 3.5%) on electrophoresis.
-
β-thalassemia major (homozygote):
- β chain is absent –> severe anemia [C] requiring blood transfusion (2° hemochromatosis).
- Marrow expansion (“crew cut” on skull x-ray) –> skeletal deformities.
- “Chipmunk” facies.
- Extramedullary hematopoiesis (leads to hepatosplenomegaly).
- Increased risk of parvovirus B19-induced aplastic crisis.
- Major –> increased HbF (α2γ2).
- HbF is protective in the infant and disease only becomes symptomatic after 6 months.
-
HbS/β-thalassemia heterozygote
- Mild to moderate sickle cell disease depending on amount of β-globin production.
-
β-thalassemia minor (heterozygote):
10
Q
Lead poisoning
- Type of condition
- Description
- Findings
A
- Type of condition
- Microcytic, hypochromic (MCV < 80 fL) anemia
- Description
- Lead inhibits ferrochelatase and ALA dehydratase –> decreased heme synthesis and increased RBC protoporphyrin.
- Also inhibits rRNA degradation, causing RBCs to retain aggregates of rRNA (basophilic stippling).
- High risk in old houses with chipped paint.
- Findings
-
LEAD:
- Lead Lines on gingivae (Burton lines) and on metaphyses of long bones [D] on x-ray.
- Encephalopathy and Erythrocyte basophilic stippling.
- Abdominal colic and sideroblastic Anemia.
-
Drops—wrist and foot drop.
- Dimercaprol and EDTA are 1st line of treatment.
-
Succimer used for chelation for kids
- It “sucks” to be a kid who eats lead.
-
LEAD:
11
Q
Sideroblastic anemia
- Type of condition
- Description
- Defect
- Causes
- Findings
- Treatment
A
- Type of condition
- Microcytic, hypochromic (MCV < 80 fL) anemia
- Description
- Defect in heme synthesis.
- Hereditary: X-linked defect in δ-ALA synthase gene.
- Causes: genetic, acquired (myelodysplastic syndromes), and reversible (alcohol is most common, lead, vitamin B6 deficiency, copper deficiency, and isoniazid).
- Defect in heme synthesis.
- Findings
- Ringed sideroblasts ([E] with iron-laden mitochondria) seen in bone marrow.
- Increased iron, normal TIBC, increased ferritin.
- Treatment
- Pyridoxine (B6, cofactor for δ-ALA synthase).
12
Q
Megaloblastic anemia
- Type of condition
- Description
- Findings
A
- Type of condition
- Macrocytic (MCV > 100 fL) anemia
- Description
- Impaired DNA synthesis –> maturation of nucleus of precursor cells in bone marrow delayed relative to maturation of cytoplasm.
- Findings
- Abnormal cell division –> pancytopenia.
13
Q
Folate deficiency
- Type of condition
- Causes
- Findings
A
- Type of condition
- Megaloblastic macrocytic (MCV > 100 fL) anemia
- Causes
- Malnutrition (e.g., alcoholics), malabsorption, antifolates (e.g., methotrexate, trimethoprim, phenytoin), increased requirement (e.g., hemolytic anemia, pregnancy).
- Findings
- Hypersegmented neutrophils, glossitis, decreased folate, increased homocysteine but normal methylmalonic acid.
- No neurologic symptoms (distinguishes from B12 deficiency).
14
Q
B12 deficiency (cobalamin)
- Type of condition
- Causes
- Findings
A
- Type of condition
- Megaloblastic macrocytic (MCV > 100 fL) anemia
- Causes
- Insufficient intake (e.g., strict vegans), malabsorption (e.g., Crohn disease), pernicious anemia, Diphyllobothrium latum (fish tapeworm), proton pump inhibitors.
- Findings
- Hypersegmented neutrophils [A], glossitis, decreased B12, increased homocysteine, increased methylmalonic acid.
-
Neurologic symptoms
- Subacute combined degeneration (due to involvement of B12 in fatty acid pathways and myelin synthesis)
- Peripheral neuropathy with sensorimotor dysfunction
- Dorsal columns (vibration/proprioception)
- Lateral corticospinal (spasticity)
- Dementia
15
Q
Orotic aciduria
- Type of condition
- Description
- Findings
A
- Type of condition
- Megaloblastic macrocytic (MCV > 100 fL) anemia
- Description
- Inability to convert orotic acid to UMP (de novo pyrimidine synthesis pathway) because of defect in UMP synthase.
- Autosomal recessive.
- Presents in children as megaloblastic anemia that cannot be cured by folate or B12 with failure to thrive.
- No hyperammonemia (vs. ornithine transcarbamylase deficiency— orotic acid with hyperammonemia).
- Findings
- Hypersegmented neutrophils, glossitis, orotic acid in urine.
- Treatment: uridine monophosphate to bypass mutated enzyme.
19
Q
Aplastic anemia
- Type of condition
- Caused by…
- Findings
- Symptoms
- Treatment
A
- Type of condition
- Nonhemolytic, normocytic anemia
- Caused by failure or destruction of myeloid stem cells due to:
- Radiation and drugs (benzene, chloramphenicol, alkylating agents, antimetabolites)
- Viral agents (parvovirus B19, EBV, HIV, HCV)
- Fanconi anemia (DNA repair defect)
- Idiopathic (immune mediated, 1° stem cell defect); may follow acute hepatitis
- Findings
- Pancytopenia characterized by severe anemia, leukopenia, and thrombocytopenia.
- Normal cell morphology, but hypocellular bone marrow with fatty infiltration [A] (dry bone marrow tap).
- Symptoms
- Fatigue, malaise, pallor, purpura, mucosal bleeding, petechiae, infection.
- Treatment
- Withdrawal of offending agent, immunosuppressive regimens (antithymocyte globulin, cyclosporine), allogeneic bone marrow transplantation, RBC and platelet transfusion, G-CSF, or GM-CSF.
26
Q
Sickle cell anemia
- Type of condition
- Description
- Pathogenesis
- Findings
- Complications in sickle cell disease (SS)
- Diagnosis
- Treatment
A
- Type of condition
- Extravascular intrinsic hemolytic normocytic anemia
- Description
- HbS point mutation causes a single amino acid replacement in β chain (substitution of glutamic acid with valine) at position 6.
- Newborns are initially asymptomatic because of increased HbF and decreased HbS.
- Heterozygotes (sickle cell trait) have resistance to malaria.
- 8% of African Americans carry the HbS trait.
- Pathogenesis
- Low O2, dehydration, or acidosis precipitates sickling (deoxygenated HbS polymerizes), which results in anemia and vaso-occlusive disease.
- Findings
- Sickled cells are crescent-shaped RBCs [A].
- “Crew cut” on skull x-ray due to marrow expansion from increased erythropoiesis (also in thalassemias).
- Complications in sickle cell disease (SS)
- Aplastic crisis (due to parvovirus B19).
- Autosplenectomy (Howell-Jolly bodies) –> increased risk of infection with encapsulated organisms
- Early splenic dysfunction occurs in childhood.
- Splenic sequestration crisis.
- Salmonella osteomyelitis.
- Painful crisis (vaso-occlusive): dactylitis. (painful hand swelling), acute chest syndrome (most common cause of death in adults), avascular necrosis, stroke.
- Renal papillary necrosis (due to low O2 in papilla; also seen in heterozygotes) and microhematuria (medullary infarcts).
- Diagnosis
- Hemoglobin electrophoresis.
- Treatment
- Hydroxyurea (increased HbF) and bone marrow transplantation.
33
Q
Heme synthesis, porphyrias, and lead poisoning (388)
- The porphyrias
- Lead
A
- The porphyrias
- Hereditary or acquired conditions of defective heme synthesis
- Lead to the accumulation of heme precursors.
- Lead
- Inhibits specific enzymes needed in heme synthesis, leading to a similar condition.
36
Q
Porphyria cutanea tarda
- Affected enzyme
- Accumulated substrate
- Presenting symptoms
A
- Affected enzyme
- Uroporphyrinogen decarboxylase
- Accumulated substrate
- Uroporphyrin (teacolored urine)
- Presenting symptoms
- Blistering cutaneous photosensitivity [A].
- Most common porphyria.
