Hematology and Diagnostic Testing Review Flashcards

Comprehensive Q&A flashcards covering principles of lab testing, hematopoiesis, red blood cell indices, anemias, iron studies, lead poisoning, hemolytic disorders, and B12/folate deficiencies.

What is the definition of sensitivity in diagnostic laboratory testing, and what rule applies to a negative result on a highly sensitive test?

Sensitivity is the probability that a test will indicate disease among those who have the disease, calculated as $\text{TP} / (\text{TP} + \text{FN}) \times 100$ or $A / (A + C) \times 100$. A negative result on a highly sensitive test effectively rules out the diagnosis (SnNout).

What is the definition of specificity in diagnostic laboratory testing, and what rule applies to a positive result on a highly specific test?

Specificity is the fraction of individuals without the disease who obtain a negative test result, calculated as $\text{TN} / (\text{TN} + \text{FP}) \times 100$ or $D / (D + B) \times 100$. A positive result on a highly specific test effectively rules in the diagnosis (SpPIn).

How are Positive Predictive Value (PPV) and Negative Predictive Value (NPV) defined, and what primary population factor influences them?

PPV is the likelihood that a positive test is truly positive ($\text{TP} / (\text{TP} + \text{FP})$), while NPV is the likelihood that a negative test is truly negative ($\text{TN} / (\text{TN} + \text{FN})$). Both predictive values are strongly influenced by the prevalence of the disease in the tested population.

In laboratory testing evaluation, how is precision distinguished from accuracy as illustrated in target diagrams?

Accuracy reflects how close test results are to true reality ($(\text{TP} + \text{TN}) / (\text{Total})$), whereas precision represents the reproducibility of results when tested repeatedly by different technologists or methods, even if those results are consistently clustered away from the true center.

Why is the term reference range preferred over normal range in clinical laboratory diagnosis?

The term reference range is preferred because it represents the range of values found in $95\%$ of a healthy reference population based on a Gaussian distribution, acknowledging that some healthy individuals naturally fall outside this interval and some ill individuals fall within it.

What are the percentage breakdowns of the cellular and liquid components of whole blood?

Whole blood consists of $55\%$ plasma (fluid) and $45\%$ formed cellular elements, which include Red Blood Cells ($45\%$), White Blood Cells ($\approx 0.5\%$), and Platelets ($\approx 0.5\%$).

What are the primary anatomical sites of hematopoiesis from embryonic development through adulthood?

In the embryo, hematopoiesis occurs in the yolk sac and liver; from months $3\text{--}7$, in the spleen; during months $4\text{--}5$, in the marrow cavity for granulocytes and platelets; in month $7$, in the marrow cavity for erythrocytes; at birth, primarily in bone marrow; and in adults, restricted to the axial skeleton (skull, ribs, sternum, vertebrae, pelvis) and proximal femur.

What hormone regulates red blood cell production, where is it produced, and what triggers its release?

Erythropoietin (EPO) is produced by kidney peritubular cells and is released in response to hypoxia (low blood oxygen levels) to stimulate bone marrow stem cells and accelerate RBC maturation.

What is a reticulocyte, what causes its polychromatic appearance on Wright stain, and what is its normal percentage in blood?

A reticulocyte is the final immature stage of RBC maturation that spends $1\text{--}2\,\text{days}$ maturing in circulation. Its polychromatic appearance on Wright stain is caused by residual cytoplasmic RNA and mitochondria. It normally accounts for $0.5\text{--}2.5\%$ of circulating RBCs.

What is the structure of hemoglobin, and how many oxygen molecules can a single red blood cell transport?

Hemoglobin consists of $4$ globin protein chains and $4$ iron-containing heme groups. Each RBC contains approximately $250\,\text{million}$ hemoglobin molecules, allowing a single RBC to transport up to $1\,\text{billion}$ oxygen ($O_2$) molecules.

What is hematocrit (Hct), and what simple formula estimates hemoglobin (Hb) level from hematocrit?

Hematocrit is the percentage of whole blood volume occupied by packed red blood cells (normal: male $42\text{--}52\%$, female $37\text{--}47\%$). Hemoglobin can be roughly estimated by dividing the hematocrit percentage by $3$ ($\text{Hb} \approx \text{Hct} / 3$).

What are the formulas and reference ranges for Mean Corpuscular Volume (MCV), Mean Corpuscular Hemoglobin (MCH), and Mean Corpuscular Hemoglobin Concentration (MCHC)?

MCV ($\text{Hct} / \text{RBC}$) measures average RBC volume ($80\text{--}100\,\text{fL}$); MCH ($\text{Hb} / \text{RBC}$) measures average Hb weight per RBC ($26\text{--}32\,\text{pg}$); and MCHC ($\text{Hb} / \text{Hct}$) measures average Hb concentration ($32\text{--}36\%$ or $\text{g/dL}$).

What does Red Cell Distribution Width (RDW) measure, and what morphological condition does an elevated RDW represent?

RDW measures the variation in size among circulating red blood cells. An elevated RDW represents anisocytosis (increased variability in red cell size).

How are poikilocytosis, target cells, schistocytes, and Howell-Jolly bodies characterized on a blood smear?

Poikilocytosis is an increased presence of abnormally shaped RBCs ($>10\%$); target cells are RBCs with central Hb clumps typical of thalassemia; schistocytes are fragmented RBCs seen in conditions like TTP; and Howell-Jolly bodies are nuclear remnants seen in functional asplenia or damaged spleens.

What is the clinical definition of anemia, and what physical sign is considered most specific during examination?

Anemia is a hematologic state where RBC count, hemoglobin, and hematocrit fall below reference ranges, reducing blood oxygen-carrying capacity. Pallor of mucous membranes is the most specific physical examination finding.

How is the Corrected Reticulocyte Count (CRC) calculated, and what Reticulocyte Production Index (RPI) threshold indicates ineffective erythropoiesis?

CRC is calculated as $\text{Hct} / 45 \times \text{Retic Count \%}$. An RPI value of $<3\%$ in the presence of anemia indicates an ineffective bone marrow erythropoietic response.

What are the classic physical signs and symptoms specific to Iron Deficiency Anemia (IDA)?

In addition to general anemia symptoms, IDA specifically presents with a red/sore tongue and mouth (glossitis), spoon-shaped nails (koilonychia), and PICA (cravings for non-food substances such as ice, soil, or raw starch).

How do Serum Ferritin, Serum Iron, Total Iron Binding Capacity (TIBC), and % Transferrin Saturation change in Iron Deficiency Anemia versus Anemia of Chronic Disease?

In IDA, Serum Ferritin is Low ($<12\,\text{mcg/L}$), Serum Iron is Low, TIBC is High, and % Transferrin Saturation is Low ($<15\%$). In Anemia of Chronic Disease, Serum Iron is Low, TIBC is Low or normal, Ferritin is Normal or High, and % Transferrin Saturation is Low.

Why is serum ferritin considered the gold standard laboratory test for evaluating iron deficiency?

Serum ferritin directly reflects tissue iron storage pools in organs like the liver, spleen, and bone marrow. It is the most sensitive marker because its concentration drops first in early iron deficiency before serum iron or Wintrobe indices decline.

What is the Mentzer Index formula, and how does it differentiate Iron Deficiency Anemia from Thalassemia?

The Mentzer Index is calculated as $\text{MCV} / \text{RBC}$. A ratio $>13$ suggests Iron Deficiency Anemia, whereas a ratio $<13$ suggests Thalassemia (where RBC count remains normal or elevated despite microcytosis).

What radiographical finding on a long bone X-ray is characteristic of chronic lead poisoning in skeletally immature patients?

Chronic lead poisoning produces epiphyseal lead lines, which appear as dense, thick sclerotic bands on the metaphyseal side of the physeal plate in growing long bones.

What red blood cell inclusion, indicated by the arrow on this blood smear, is classically associated with lead poisoning?

The arrow indicates basophilic stippling, which consists of coarse blue specks/granules within red blood cells caused by lead-induced inhibition of RNA degradation.

What blood lead level thresholds require chelation therapy and immediate hospitalization according to clinical guidelines?

Blood lead levels between $45\text{--}69\,\text{mcg/dL}$ indicate potential need for chelation therapy, whereas blood lead levels $>70\,\text{mcg/dL}$ require urgent hospitalization and immediate chelation therapy.

What genetic defect, RBC shape change, and indices define Hereditary Spherocytosis?

Hereditary Spherocytosis is an inherited RBC membrane disorder causing loss of membrane surface area and biconcavity, resulting in rigid microspherocytes and a microcytic, hyperchromic anemia (low MCV, elevated MCHC).

What laboratory findings on a chemistry panel and urinalysis confirm active intravascular or extravascular hemolysis?

Active hemolysis shows increased unconjugated (indirect) bilirubin, elevated Lactate Dehydrogenase (LDH, $3\text{--}5\times$ normal), decreased serum haptoglobin, increased urine urobilinogen, and positive hemoglobinuria on urinalysis.

What amino acid substitution causes Hemoglobin S, and how do Sickle Cell Trait (Hb AS) and Sickle Cell Anemia (Hb SS) differ clinically?

Hemoglobin S is caused by a point mutation replacing glutamic acid with valine at position $6$ of the beta-globin chain. Sickle Cell Trait (Hb AS, heterozygous) is usually asymptomatic except under severe hypoxia/exercise, while Sickle Cell Anemia (Hb SS, homozygous) causes severe painful vaso-occlusive crises, target cells, sickled cells, and severe chronic anemia.

What enzyme deficiency causes episodic hemolysis after exposure to fava beans or sulfa drugs, and what key microscopic features are seen on special stain?

Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency is an X-linked recessive disorder preventing NADPH generation under oxidative stress. Blood smears display bite cells and Heinz bodies (visible with special crystal violet stain).

What is Aplastic Anemia (hypoplastic bone marrow), and what CBC pattern results from complete marrow suppression?

Aplastic Anemia is an autoimmune or toxin-induced destruction of hematopoietic stem cells where active marrow is replaced by fat or fibrous tissue, resulting in pancytopenia (erythropenia, leukopenia, and thrombocytopenia).

How is Vitamin B12 absorbed in the digestive tract, and how long do hepatic B12 stores last before deficiency occurs?

Vitamin B12 is liberated from food by gastric HCl, binds Intrinsic Factor (secreted by gastric parietal cells), and is absorbed in the terminal ileum. Large hepatic stores preserve B12 levels for $2\text{--}5\,\text{years}$ before depletion.

What is Pernicious Anemia, and how do Intrinsic Factor Antibody and Parietal Cell Antibody tests differ in sensitivity and specificity?

Pernicious Anemia is an autoimmune destruction of gastric parietal cells or Intrinsic Factor (IF). The Intrinsic Factor Antibody Test has low sensitivity ($\approx 50\%$) but high specificity (rules in disease), whereas the Parietal Cell Antibody Test is highly sensitive ($\approx 90\%$) but less specific (positive in $10\%$ of healthy controls and gastritis).

How do Methylmalonic Acid (MMA) and Homocysteine levels distinguish Vitamin B12 deficiency from Folate (Vitamin B9) deficiency?

In Vitamin B12 deficiency, both Serum MMA and Homocysteine are Elevated. In Folate deficiency, Serum Homocysteine is Elevated, but Serum MMA remains Normal.

What primary clinical feature distinguishes Vitamin B12 deficiency from Folate deficiency?

Vitamin B12 deficiency causes progressive, potentially irreversible neurological signs and symptoms (numbness, paresthesias, diminished vibration/position sense, ataxia, cognitive changes), whereas Folate deficiency presents with identical macrocytic anemia and GI symptoms but completely lacks neurological involvement.

Why is administering high-dose Folate therapy alone dangerous in a patient with unconfirmed macrocytic anemia?

Folate supplementation bypasses the B12-dependent step in nucleic acid synthesis, correcting the megaloblastic RBC morphology and anemia while allowing uncorrected Vitamin B12 deficiency to silently continue causing permanent, irreversible neurological damage (Folate masking B12 deficiency).