DNA Metabolism and Hemolysis Practice Flashcards

A set of 100 vocabulary flashcards covering DNA metabolism, Vitamin B12 and Folate deficiencies (Megaloblastic Anemia), and the basics of Intravascular and Extravascular Hemolysis.

Megaloblastic Anemia (MA)

A type of macrocytic anemia whose root cause is impaired DNA synthesis, resulting in very large erythroid cells in the bone marrow.

Megaloblasts

Very large erythroid cells found in the bone marrow of patients with Megaloblastic Anemia.

Thymidine nucleotide synthesis

The specific biochemical process impaired in Megaloblastic Anemia due to a deficiency of Vitamin $B_{12}$ or folate.

dUMP Methylation

The specific step in nucleotide synthesis that is directly prevented by a folate deficiency.

THF (Tetra-hydrofolate)

A folate derivative whose production is indirectly prevented by a Vitamin $B_{12}$ deficiency.

Uracil

The nucleotide incorporated into DNA in place of thymidine when thymidine is lacking, leading to DNA fragmentation and apoptosis.

Cobalamin

Another name for Vitamin $B_{12}$, which is structurally a tetrapyrrole.

Corrin rings

The four ring structures that, along with one central cobalt atom, make up the structure of Vitamin $B_{12}$.

Cobalt

The specific atom found in the middle of the corrin rings in a Vitamin $B_{12}$ molecule.

Hydroxycobalamin and Cyanocobalamin

Analogs of Vitamin $B_{12}$ that are often found in food and supplements.

Methylcobalamin

A coenzyme form of Vitamin $B_{12}$ used in the transfer of methyl groups to homocysteine.

$$5' \text{-deoxyadenosylcobalamin}$$

A coenzyme form of Vitamin $B_{12}$ required for the conversion of methylmalonyl CoA to succinyl CoA.

Folic Acid

A molecule consisting of a pteridine ring attached to para-aminobenzoate with one or more glutamate residues.

$$5\text{-methyl-THF}$$

The specific form in which folate circulates in the bloodstream.

Methylmalonyl CoA Mutase

The enzyme that catalyzes the conversion of methylmalonyl CoA to succinyl CoA using Vitamin $B_{12}$ as a cofactor.

Methionine Synthase

The enzyme that catalyzes the transfer of a methyl group from $5\text{-methyl-THF}$ to homocysteine to generate methionine.

Methionine

The amino acid generated when a methyl group is transferred from $5\text{-methyl-THF}$ to homocysteine.

Homocysteine

The substrate that receives a methyl group to become methionine in a reaction linked to Vitamin $B_{12}$ and folate.

Reticulocytosis

An increase in reticulocytes in the blood, which may cause a macrocytic non-megaloblastic anemia.

Oval Macrocytes

Large, egg-shaped red blood cells characteristic of the peripheral blood smear in Megaloblastic Anemia.

Hypersegmented Neutrophils

Neutrophils with five or more nuclear lobes, a hallmark finding on the PBS of patients with Megaloblastic Anemia.

Pancytopenia

A laboratory finding in Megaloblastic Anemia where RBC, WBC, and platelet counts are all decreased.

Intrinsic Factor (IF)

A protein necessary for Vitamin $B_{12}$ absorption; its absence leads to Pernicious Anemia.

Diphyllobothrium latum

A parasite (fish tapeworm) that competes for available Vitamin $B_{12}$, potentially causing a deficiency.

Blind Loop Syndrome

A condition involving bacterial overgrowth in the intestine that causes competition for Vitamin $B_{12}$.

Nuclear-cytoplasmic asynchrony

A condition where nuclear maturation lags behind cytoplasmic maturation due to impaired DNA synthesis.

Glossitis

A clinical symptom of Vitamin $B_{12}$ or folate deficiency involving loss of tongue epithelium, resulting in a smooth, sore surface.

Neural Tube Defects (NTDs)

Impairments in the formation of the fetal nervous system, such as Spina Bifida, caused by folate deficiency during pregnancy.

2.4 \text{ } \bmu\text{g}

The recommended daily intake of Vitamin $B_{12}$.

$$400\text{ } \text{mg}$$

The recommended daily intake of folic acid as listed in the transcript.

Haptocorrin

A protein from which Vitamin $B_{12}$ must be separated to bind with Intrinsic Factor for absorption.

Imerslund-Gr$asbeck syndrome

An inherited error involving the absorption and transport of Vitamin $B_{12}$.

Transcobalamin Deficiency

An inherited disorder that impairs the transport of Vitamin $B_{12}$ in the blood.

Heat-labile

A characteristic of Folate, meaning overcooking food can diminish its nutritional value.

Celiac Disease

A condition of the small intestine that can result in the impaired absorption of folate.

50\text{ } \bmu\text{m}

The actual daily requirement for folate according to the transcript (listed as $50\text{ } \text{mg}$).

Methotrexate

A drug that impairs folate metabolism by decreasing its absorption or use.

Renal Dialysis

A medical procedure that can cause excessive folate loss in the dialysate, necessitating supplementation.

Myelodysplastic Syndrome (MDS)

A cause of megaloblastosis that is refractive to therapy with either Vitamin $B_{12}$ or Folate.

Acute Erythroid Leukemia (AEL)

An acquired mutation in progenitor cells that causes megaloblastosis independent of vitamin levels.

$$100-150\text{ } \text{fL}$$

The common range for Mean Cell Volume (MCV) in Megaloblastic Anemia.

MCHC

Mean Cell Hemoglobin Concentration, which typically remains normal in Megaloblastic Anemia because cytoplasmic development is unaffected.

Howell-Jolly (HJ) Bodies

Nuclear remnants found in RBCs on a peripheral blood smear, often seen in Megaloblastic Anemia.

Basophilic Stippling

A PBS finding in Megaloblastic Anemia characterized by small blue dots within the RBC representing RNA precipitates.

IF-blocking antibodies

Specific antibodies against intrinsic factor used as a diagnostic tool for Pernicious Anemia.

Parietal Cells

Cells in the stomach that produce intrinsic factor and can be lost in Pernicious Anemia.

Serum Gastrin

A hormone that can be markedly elevated in Pernicious Anemia and used as a diagnostic test.

Achlorhydria

The absence of hydrochloric acid in gastric secretions, a feature of Pernicious Anemia.

Holotranscobalamin Assay

A specific diagnostic test for Vitamin $B_{12}$ status that measures the active form of the vitamin.

Round Macrocytes

Large red blood cells that lack the oval shape, typically seen in non-megaloblastic macrocytic anemias.

Non-megaloblastic macrocytosis

An increase in RBC size where DNA synthesis is unimpaired, commonly caused by liver disease or alcoholism.

Anemia of Alcoholism

A macrocytic anemia where ethanol has direct toxic effects on precursor cells and red cell morphology.

Stomatocytes

A red cell morphology change associated with the direct toxic effects of chronic alcohol consumption.

Acanthocytes

Also known as Spur Cells, these are characteristic of liver disease caused by alcoholism.

Spur Cell Anemia

A condition characterized by round macrocytes and acanthocytes in the peripheral blood due to liver disease.

Vacuolization

A change in erythroblasts within the bone marrow caused by the toxic effects of ethanol.

Hemolysis

The increased rate of destruction (lysis) of RBCs, resulting in a shortened life span.

Hemolytic Anemia

A condition resulting when the rate of RBC destruction exceeds the increased rate of RBC production by the bone marrow.

Acute Hemolysis

A sudden, rapid onset of RBC destruction, such as in Paroxysmal Nocturnal Hemoglobinuria (PNH).

Chronic Hemolysis

A long-term shortening of RBC life span that may be hidden if the bone marrow can compensate.

G6PD Deficiency

A metabolic pathway defect causing chronic hemolysis that can become acute when the patient is challenged with oxidizing agents.

Inherited Hemolytic Disorders

Disorders passed to offspring by mutant genes, such as thalassemia.

Acquired Hemolytic Disorders

Hemolytic conditions that develop in previously normal individuals, such as those caused by malaria.

Intrinsic RBC Defects

Defects located within the RBC (membrane, metabolic pathways, or Hb molecule) that cause hemolysis.

Extrinsic RBC Defects

RBC destruction caused by external factors, such as traumatic, microangiopathic, or infectious agents.

Intravascular Hemolysis (IV)

RBC fragmentation that occurs mainly within the blood stream.

Extravascular Hemolysis (EV)

Also known as macrophage-mediated hemolysis, where RBCs are engulfed and lysed inside phagocytes.

Haptoglobin

A protein part of the salvage system that binds free hemoglobin in the plasma.

Hemopexin

A protein that binds free heme to prevent oxidative damage and salvage iron.

Haptoglobin-hemopexin-methemalbumin system

The collective mechanisms used to salvage hemoglobin iron and prevent oxidation during hemolysis.

Unconjugated hyperbilirubinemia

A laboratory finding characteristic of excessive extravascular (macrophage-mediated) hemolysis.

Urobilinogen

A breakdown product of bilirubin found in increased levels in urine and feces during excessive extravascular hemolysis.

Hemoglobinemia

The presence of free hemoglobin in the serum, a hallmark of intravascular hemolysis.

Hemoglobinuria

The presence of free hemoglobin in the urine, indicating significant intravascular hemolysis.

Hemosiderinuria

The presence of iron-containing pigment in the urine, detected by Prussian blue staining of urine sediment.

Methemalbuminemia

The presence of methemalbumin in the blood, indicating intravascular hemolysis.

Schistocytes

Fragmented RBCs often present in cases of intravascular hemolysis, such as microangiopathic hemolytic anemia.

Spherocytes

Small, spherical RBCs often seen in extravascular hemolysis or hereditary spherocytosis.

Splenomegaly

An enlargement of the spleen, often appearing as a clinical feature of severe chronic hemolysis.

Gallstones

A clinical complication of severe anemia and chronic hemolysis due to high bilirubin turnover.

Oliguria

A clinical symptom of severe anemia characterized by reduced urine output.

Prussian blue staining

A laboratory technique used on urine sediment to confirm hemosiderinuria.

LDH (Lactate Dehydrogenase)

An enzyme found in RBCs that is significantly increased in the serum during both MA and hemolysis.

Elliptocytes

Oval-shaped RBCs associated with Hereditary Elliptocytosis.

Burr Cells

RBC morphology associated with Pyruvate Kinase deficiency or uremia.

Cold Agglutinins

Antibodies that cause RBC agglutination in immunohemolytic diseases.

Erythrophagocytosis

The ingestion of RBCs by macrophages, often due to damage to the RBC surface.

$$1\%$$

The approximate percentage of RBCs removed daily through normal macrophage-mediated hemolysis.

$$10\%-20\%$$

The percentage of normal RBC destruction that occurs via intravascular fragmentation.

Bilirubin

The yellow breakdown product of hemoglobin that increases in the serum during hemolysis.

Hb scavengers

Molecules like haptoglobin and hemopexin that bind free hemoglobin and heme.

Macrocytosis

A condition where RBCs have an MCV greater than $100\text{ } \text{fL}$.

Polychromasia

An increase in immature RBCs (reticulocytes) that stain bluish, which is typically not observed in MA but seen in hemolysis.

PBF

Peripheral Blood Film, another term for a peripheral blood smear (PBS).

Ineffective Erythropoiesis

A condition in MA donde erythroid precursors are destroyed in the bone marrow before maturing.

Methylmalonyl CoA

The substrate that accumulates in Vitamin $B_{12}$ deficiency because it cannot be converted to Succinyl CoA.

Succinyl CoA

The metabolic product generated from Methylmalonyl CoA in a B12-dependent reaction.

Anti-IF Antibodies

Antibodies used in the laboratory to help diagnose Pernicious Anemia.

Gastrointestinal Tract Epithelium

The tissue whose loss can result in gastritis, nausea, and constipation in patients with MA.

Neural Tube

The embryonic precursor to the central nervous system that fails to close properly in folate deficiency.