RBC Kinetics, Metabolism, Membrane Physiology, and Iron

Flashcards covering RBC kinetics, metabolic pathways, membrane structure, hemoglobin biochemistry, and iron homeostasis based on the clinical science lecture notes.

Erythrokinetics

The study of the generation and life cycle of erythrocytes (RBCs).

Hypoxia

The primary stimulant for erythropoiesis in the body.

Erythropoietin (EPO)

A glycoprotein and true hormone that stimulates early release of reticulocytes and inhibits apoptosis.

Apoptosis

Programmed cell death that is inhibited by erythropoietin (EPO) during erythropoiesis.

Marrow transit time

The time reticulocytes spend in the bone marrow, which is reduced by the action of erythropoietin (EPO).

Cytokines

Chemical signals produced by macrophages that act as stimulants for erythropoiesis.

Embden-Meyerhof Pathway

The primary anaerobic glycolytic pathway used by RBCs to generate ATP.

Hexose Monophosphate Shunt

A pathway that detoxifies accumulated peroxide and diverts glucose-6-phosphate ($G6P$) to pentose phosphate.

Glucose-6-phosphate dehydrogenase (G6PD)

The enzyme that diverts $G6P$ into the Hexose Monophosphate Shunt; its deficiency is the most common RBC enzyme deficiency.

Heinz bodies

Inclusions within RBCs consisting of precipitated hemoglobin, often associated with $G6PD$ deficiency.

Degmacytes

Also known as 'Bite cells,' these are RBCs that have had Heinz bodies removed by the spleen.

Methemoglobin Reductase Pathway

The metabolic pathway responsible for maintaining hemoglobin iron in the ferrous ($Fe^{2+}$) state.

Methemoglobin

A form of hemoglobin where the iron atom is in the ferric ($Fe^{3+}$) state, rendering it unable to bind oxygen.

Cytochrome b5 reductase

An enzyme in the Methemoglobin Reductase Pathway that reduces methemoglobin back to functional hemoglobin.

Rapoport-Luebering Pathway

A diversion from the glycolysis pathway that produces $2,3\text{-}BPG$ (or $2,3\text{-}DPG$).

2,3-Bisphosphoglycerate ($2,3\text{-}BPG$)

A molecule that binds to the globin chains of Hgb to maintain it in a deoxygenated form and facilitate oxygen delivery.

1,3-Bisphosphoglycerate ($1,3\text{-}BPG$)

The glycolytic intermediate from which $2,3\text{-}BPG$ is diverted.

Bisphosphoglycerate mutase (BPGM)

The enzyme that converts $1,3\text{-}BPG$ into $2,3\text{-}BPG$; it is inhibited by low pH and low ATP.

Bisphosphoglycerate phosphatase (BPGP)

The enzyme that returns $2,3\text{-}BPG$ to the glycolysis path, activated by low pH and low ATP.

Biconcave discoid

The shape of an erythrocyte which generates 40% excess surface area compared to a sphere.

Deformability

The property of RBCs to stretch up to 2.5 times their resting diameter to pass through narrow capillaries.

Splenic microvessels

Vessels measuring approximately 3\text{\thinspace}\text{\textmu m} that RBCs must pass through to avoid destruction.

Integral proteins

Transmembrane proteins that form complexes with skeletal proteins to maintain membrane vertical stability.

Ankyrin complex

A major integral protein complex involved in maintaining the vertical stability of the RBC membrane.

Actin junctional complex

Also known as the protein 4.1 complex, it is an integral protein complex essential for membrane stability.

Peripheral proteins

Cytoskeletal proteins, mainly filamentous $\alpha$-spectrin and $\beta$-spectrin, that maintain membrane elasticity.

$\alpha$-spectrin

A filamentous peripheral protein that forms lateral heterodimers to regulate RBC mechanical stability.

$\beta$-spectrin

A filamentous peripheral protein that works with $\alpha$-spectrin to maintain membrane elasticity.

Hereditary elliptocytosis

A condition resulting from a deficiency or defect in lateral membrane protein interactions.

Hereditary spherocytosis

A condition resulting from a deficiency or defect in vertical membrane proteins, leading to a loss of RBC rebound ability.

Aquaporin

A membrane protein that regulates internal osmotic pressure by directing water inward.

$$Na^{+}\text{-}ATPase$$

A cation pump that helps maintain the selective permeability of the RBC membrane against sodium.

$$K^{+}\text{-}ATPase$$

A cation pump that helps maintain intracellular potassium levels.

$$Ca^{2+}\text{-}ATPase$$

A pump that expels calcium from the RBC to maintain low intracellular levels ($30\text{ to }60\text{\thinspace}nM$).

Globin

The polypeptide portion of hemoglobin synthesized through the expression of globin genes.

Helices A-H

The eight helical structures that make up each globin chain in a hemoglobin molecule.

F8 Histidine

The proximal histidine residue to which the heme molecule binds in the globin chain.

E7 Histidine

The distal histidine residue that provides space for heme to sit in the globin crevice.

Heme

A tetra-pyrolic structure with a central iron atom that binds one molecule of oxygen.

$$Fe^{2+}$$

The ferrous state of iron required for binding oxygen in the heme molecule.

$$1.34\text{\thinspace}mL$$

The amount of oxygen that can be bound by each hemoglobin molecule.

Mitochondria

The cellular site where heme synthesis begins.

Cytoplasm

The location in erythroid precursors where heme and globin combine to form a full Hb molecule.

Quaternary structure

The complete structure of hemoglobin consisting of four polypeptide chains (e.g., $\alpha_{1}\beta_{1}$ and $\alpha_{2}\beta_{2}$).

$\alpha$ gene

The gene located on chromosome 16 responsible for alpha globin synthesis.

$\beta$ gene

The gene located on chromosome 11 responsible for beta globin synthesis.

Ferrochelatase

The enzyme responsible for the incorporation of ferrous iron ($Fe^{2+}$) into protoporphyrin IX.

Protoporphyrin IX

The precursor molecule that combines with iron to form heme.

Hgb A

The major type of adult hemoglobin, composed of two alpha and two beta chains.

Hgb A2

A normal type of adult hemoglobin present in smaller amounts than Hgb A.

Hgb F

Fetal hemoglobin, which is the primary hemoglobin during intrauterine life and at birth.

Gower-1

A type of intrauterine hemoglobin present during early development.

Gower-2

A type of intrauterine hemoglobin.

Portland

A type of intrauterine hemoglobin.

Oxygen Dissociation Curve

A graph showing the relationship between partial pressure of oxygen ($P_{O2}$) and hemoglobin saturation.

$$P_{50}$$

The partial pressure of oxygen at which hemoglobin is 50% saturated, normally around $27\text{\thinspace}mmHg$.

Shift to the left

A change in the oxygen dissociation curve where $P_{50} < 27\text{\thinspace}mmHg$, indicating higher oxygen affinity.

Shift to the right

A change in the oxygen dissociation curve where $P_{50} > 27\text{\thinspace}mmHg$, indicating lower oxygen affinity.

Bohr effect

The inverse relationship between hemoglobin's oxygen binding affinity and the concentration of acidity ($H^{+}$) or carbon dioxide.

Heme iron

Dietary iron from animal sources that is highly bioavailable and efficiently absorbed.

Non-heme iron

Dietary iron from vegetable sources that is less efficiently absorbed.

Citrus

An example of an acidic food that enhances iron absorption.

Oxalates

A substance that inhibits the absorption of dietary iron.

Phytates

A substance found in foods like grains that inhibits iron absorption.

Duodenal cytochrome b (Dcytb)

A ferrireductase that reduces ferric iron ($Fe^{3+}$) to ferrous iron ($Fe^{2+}$) at the intestinal luminal membrane.

Divalent metal transporter 1 (DMT1)

The transporter that moves ferrous iron ($Fe^{2+}$) across the luminal membrane into the enterocyte.

Heme transporter

A membrane protein that absorbs heme as a complete unit into the enterocyte.

Heme oxygenase-1 (HO-1)

The enzyme that removes iron from the heme molecule inside the enterocyte.

Ferroportin

The protein that carries iron out of the enterocyte, macrophage, or hepatocyte into the blood.

Hephaestin

A protein that reoxidizes iron from $Fe^{2+}$ to $Fe^{3+}$ as it exits the enterocyte into the blood.

Hepcidin

A hepatic protein that inhibits ferroportin to regulate and lower blood iron levels.

Transferrin

A transport protein from the liver that binds and carries ferric iron ($Fe^{3+}$) to erythropoietic cells.

Apotransferrin

The form of transferrin before it has bound iron.

$$Fe^{3+}$$

The ferric state of iron, which is the form bound by transferrin and stored in ferritin.

Ferritin

The primary storage form of iron, consisting of ferric iron atoms inside a cage-like protein.

Apoferritin

The protein cage that surrounds iron atoms to create the ferritin storage complex.

Hemosiderin

A degraded form of ferritin that is metabolically less available for use.

Serum iron

A laboratory measurement indicating the amount of iron currently being transported in the blood.

Diurnal variation

The phenomenon where serum iron levels are highest in the morning, requiring fasting specimens for accuracy.

Total iron binding capacity (TIBC)

An indirect laboratory indicator of serum transferrin levels.

Acute phase reactant (APR)

A classification for substances like ferritin whose levels increase during acute inflammation or infection.

Serum transferrin receptors (sTfR)

A measurable form of the receptor that increases in plasma when intracellular iron is low.

Free erythrocyte protoporphyrin (FEP)

Protoporphyrin IX that remains unbound to iron due to iron deficiency.

Zinc protoporphyrin (ZPP)

A complex formed when protoporphyrin IX binds to zinc instead of iron, occurring during iron deficiency.

Hemoglobin iron (total body)

The portion of whole-body iron content (approx. $2500\text{\thinspace}mg$) found in circulating RBCs.

Storage iron (total body)

The portion of whole-body iron content (approx. $1000\text{\thinspace}mg$) kept as ferritin and hemosiderin.

Salvage iron

The iron recycled daily from old RBCs (approx. $20\text{\thinspace}mg$) for new erythropoiesis.

Dietary iron ingestion

The average daily intake of iron, which ranges from $10\text{ to }14\text{\thinspace}mg$.

Dietary iron absorption

The amount of iron actually taken up by the body daily, ranging from $0.5\text{ to }2\text{\thinspace}mg$.

Iron losses

The daily amount of iron excreted or lost by the body, typically $1\text{ to }2\text{\thinspace}mg$.

Yolk sac

The initial site of blood cell production during early intrauterine life.

Liver and Spleen

Intermediate sites of blood cell production during fetal development.

Bone marrow

The primary site of blood cell production starting around birth and continuing throughout life.

Hexokinase

The enzyme that converts glucose to glucose-6-phosphate in the Embden-Meyerhof Pathway.

Myoglobin

A protein mentioned as a factor in oxygen dissociation curve shifts, containing approx. $300\text{\thinspace}mg$ of body iron combined with other proteins.

Lactate dehydrogenase (LDH)

The enzyme that converts pyruvate to lactate using $NADH$ in RBC metabolism.

Glutathione (GSH)

A molecule in the $NADPH$ system used to neutralize peroxides in the RBC.

Phosphofructokinase (PFK)

An enzyme in the Embden-Meyerhof Pathway that converts fructose-6-phosphate into fructose-1,6-diphosphate.

Pyruvate kinase (PK)

An enzyme in the final steps of glycolysis that produces ATP while converting phosphoenolpyruvate to pyruvate.

6-Phosphogluconate dehydrogenase (6PGD)

An enzyme in the Hexose Monophosphate Shunt that helps produce ribulose-5-phosphate.