Week 18 RAT

OMK Week 18 PLOs Block 3

White Blood Cell Count

measures total leukocytes; used to detect infection, inflammation, and other hematologic disorders

Red Blood Cell Count

number of red blood cells per microliter of blood; normal male 4.3–6.0 ×10⁶/µL, female 3.5–5.5 ×10⁶/µL; decreased in chronic blood loss, iron, folate, or B12 deficiency

Hemoglobin

amount of hemoglobin in blood; normal male 13.6–17.5 g/dL, female 12.0–15.5 g/dL; decreased in decreased heme synthesis or anemia

Hematocrit

percentage of blood volume occupied by RBCs; normal male 39–49%, female 35–45%; decreased in iron, B12, and folate deficiency

Mean Cell Volume

average RBC size (fL); normal 80–100 fL; decreased (microcytic)=iron deficiency, increased (macrocytic)=folate or B12 deficiency

Mean Corpuscular Hemoglobin

average hemoglobin per RBC (pg); normal 29 ± 2 pg; decreased in iron deficiency

Mean Corpuscular Hemoglobin Concentration

hemoglobin per RBC volume (g/dL); normal 34 ± 2 g/dL; decreased in iron deficiency

Red Cell Distribution Width

variation in RBC size (%); normal 13 ± 1.5%; increased in iron, folate, or B12 deficiency

Platelet Count

total platelets per µL; assesses bleeding risk or marrow function

Poikilocytosis

variation in RBC shape

Anisocytosis

variation in RBC size

Peripheral Smear Evaluation

shape (round vs ovalocytes/spherocytes/echinocytes), size (7–8 µm normal; micro- or macrocytic abnormal), color (1/3 central pallor; hypo- vs hyperchromic), inclusions (Heinz bodies = G6PD deficiency; nucleated RBCs = severe hemolysis/hypoxemia; parasites = malaria/babesiosis)

Serum Iron

circulating iron bound to transferrin; men 55–160 µg/dL, women 40–155 µg/dL

Ferritin

reflects iron stores and acts as acute-phase reactant; men 20–248 ng/mL, women 20–150 ng/mL

Total Iron-Binding Capacity

indirect measure of transferrin; normal 250–400 µg/dL

Transferrin Saturation

percentage of transferrin bound by iron = (serum iron/TIBC)×100; decreased in iron deficiency, increased in iron overload

Reticulocyte Count

percentage of young RBCs with residual RNA; normal 1 ± 0.5%

Corrected Reticulocyte Count

retic % × (patient Hct/normal Hct)

Reticulocyte Production Index

corrected retic % / maturation time; RPI >3 adequate response, <2 inadequate

Anemia

Hb <13 g/dL (men >15 y), <12 g/dL (women >15 y), <11 g/dL (pregnant or child 6–59 mo)

Kinetic Causes of Anemia

decreased RBC production (iron/B12/folate deficiency), increased destruction (hemolysis), blood loss (acute/chronic)

Morphologic Causes of Anemia

microcytic <80 fL (iron deficiency, thalassemia); normocytic 80–100 fL (acute loss, chronic disease); macrocytic >100 fL (folate/B12 deficiency)

Acid

Base Definition

Major Blood Buffers

bicarbonate, phosphate, and proteins (hemoglobin, albumin)

Bicarbonate Buffer

primary ECF buffer system (H₂CO₃/HCO₃⁻)

Phosphate Buffer

important in renal tubules and ICF

Protein Buffer

hemoglobin and albumin bind H⁺ to buffer plasma and RBCs

Ammonia Buffer

kidney mechanism excreting H⁺ as NH₄⁺

Arterial CO₂ Effect on pH

An increase in arterial CO₂ (hypercapnia) causes blood pH to decrease (become more acidic) because CO₂ combines with water to form carbonic acid (H₂CO₃), which dissociates into H⁺ and HCO₃⁻.
A decrease in arterial CO₂ (hypocapnia) causes blood pH to increase (become more alkaline) due to reduced carbonic acid formation.

Henderson-Hasselbalch Equation

pH = pKa + log ([HCO₃⁻]/(0.03×PaCO₂)); pH depends on ratio of metabolic base to respiratory acid

Penetrance

proportion of individuals with genotype who express phenotype; complete = all express, incomplete = some do not

Variable Expressivity

degree or severity of phenotype varies among individuals with same genotype

Pleiotropy

single gene mutation causes multiple unrelated phenotypic effects across organs/systems

Genetic Heterogeneity

similar phenotype arises from mutations in different genes (locus) or different mutations in same gene (allelic)

Spontaneous Mutation

de novo mutation arising in parent germ cell or early embryo; not in parents; low sibling recurrence risk

Delayed Age of Onset

mutation expresses phenotype later in life → pedigree appears to skip generations

Polymerase Chain Reaction Purpose

amplify specific DNA segment for sequencing, mutation detection, forensics, or diagnostics

PCR Mechanism

denaturation → annealing of primers → extension by thermostable DNA polymerase; each cycle doubles target DNA

Linkage

genes close on same chromosome inherited together (non-independent assortment)

Recombination Frequency

proportion of gametes with crossover between loci; reflects genetic distance; 0% = tight linkage, 50% = unlinked

Pedigree Probability Calculation

determine inheritance mode, assign genotypes, apply Mendelian probabilities adjusted for penetrance, age, and recombination

Iron Absorption Site

duodenum and upper jejunum; heme iron absorbed via heme transporter; non-heme requires reduction to Fe²⁺ by duodenal cytochrome B

Iron Transport

apical uptake via DMT1 → stored as ferritin or exported by ferroportin; hephaestin oxidizes Fe²⁺ to Fe³⁺ → binds transferrin

Hepcidin Regulation

high hepcidin → ferroportin degradation → ↓ absorption; low hepcidin → ↑ ferroportin activity → ↑ absorption

Iron Storage

ferritin (soluble) and hemosiderin (insoluble); stored in liver, spleen, bone marrow, macrophages

Iron Excretion

no regulated excretory pathway; loss via epithelial sloughing, menstruation, sweat; balance maintained by absorption control

Vitamin B12 Absorption

terminal ileum; requires intrinsic factor from parietal cells; needs pancreatic enzymes and intact ileum; absorbed as B12-IF complex → transcobalamin II in blood

Vitamin B6 Absorption

jejunum and ileum by passive diffusion; converted to PLP in liver; impaired by alcohol, isoniazid, OCPs; loss in dialysis

Folate Absorption

proximal jejunum via PCFT after polyglutamate hydrolysis; circulates as 5-methyl-THF; impaired by alcohol, phenytoin, OCPs, celiac disease, heat destruction

Heme Synthesis Pathway

glycine + succinyl-CoA → ALA (via ALAS) → PBG → uroporphyrinogen III → coproporphyrinogen III → protoporphyrin IX → Fe²⁺ insertion by ferrochelatase → heme

Heme Synthesis Regulation

rate-limiting ALAS step controlled by iron, erythropoietin, heme feedback; pathway responds to cellular heme demand

Porphyrias

inherited enzyme defects in heme pathway → precursor accumulation → neuro and photosensitivity symptoms; often autosomal dominant with low penetrance

Unconjugated Bilirubin

produced from heme breakdown in macrophages; water-insoluble, albumin-bound; elevated in hemolysis or impaired uptake/conjugation

Conjugated Bilirubin

formed in liver by bilirubin glucuronidation; water-soluble, excreted in bile/urine; elevated in cholestasis or biliary obstruction

Chronic Lead Exposure

inhibits ALAD and ferrochelatase → accumulated ALA and protoporphyrin; ↓ heme synthesis → microcytic anemia and Zn-protoporphyrin formation

Pentose Phosphate Pathway Purpose

produce NADPH and ribose-5-phosphate for nucleotide synthesis

PPP Oxidative Phase

irreversible; G6P → 6-phosphogluconate → ribulose-5-P + 2 NADPH + CO₂; rate-limiting enzyme = G6PD; inhibited by NADPH

PPP Non-Oxidative Phase

reversible interconversions via transketolase/transaldolase; produce ribose-5-P and glycolytic intermediates (F6P, G3P); driven by substrate need

PPP Tissue Use

liver and adipose use oxidative phase for NADPH; rapidly dividing cells favor non-oxidative phase for nucleotides

base

Substance that accepts hydrogen ions or donates hydroxide ions (OH⁻); has a pH > 7; decreases [H⁺] concentration.