Erythrocytes

102問 • 1年前

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A. Production: Collection of all stages of erythrocytes throughout the body; the developing precursors in the bone marrow, circulating erythrocytes in the peripheral blood and vascular spaces within organs, such as the spleen

Erythron

Progenitors, Precursors, Immature RBCs, Mature RBCs

Progenitors

BFU-E, CFU-E

Erythroid Precursors

Pronormoblast, Orthochromic Normoblast

Can be seen in the Bone Marrow

Progenitors, Precursors, Immature RBCs

Immature RBC

Reticulocyte

Can be seen in the Blood

Reticulocyte, Mature RBCs

Three Erythroid Precursors Nomenclature Systems

Normoblastic, Rubriblastic, Erythroblastic

Requirements for Growth and Maturation

Healthy Bone Marrow, EPO- Produced by Kidneys, GM-CSF, IL-3, Other Hormones: GH, Insulin, Thyroxin, Androgens

BFU-E --> RBC: Maturation days?

18-21 Days

Pronormoblast --> RBC: How many days?

6 days

In 1 BFU-E, how many RBC production?

16 RBC

Growth Requirements

Iron, Vitamin B12, Folic Acid, Mg, Co, Zn, Vit B6, Vit D, Panthotenic Acid, Intrinsic Factor

• Heme Synthesis • Hemoglobin

Iron

Nuclear Maturation

Vitamin B12 Cobalamine, Folic Acid

- Found in the parietal cells of the stomach - Vitamin B12 Absorption.

Intrinsic Factor

- Decreased oxygen state - Detected by peritubular fibroblasts of the kidney - Low level of tissue oxygen

Hypoxia

Oxygen sensor of the body

Kidney

Source of EPO Production, Functions and Regulation

Kidney

The BFU-E & CFU-E progenitors, proliferation/differentiation will turn into

Pronormoblast

EPO Production Specific Actions: Promotes the early release of retics into the circulation (Normally it is _______, but if there is a great demand it will be shortened to 1 day = shift retics)

1-2 Days

The reticulocyte will stay into the Bone Marrow for about _______, and after that it will be released to the blood.

1-2 Days

No RBC Production

Anemic

It takes how many days for Pronormoblast to be an RBC?

6 days

Reducing the time needed for cells to mature in the bone marrow. It is called?

Accelerated Erythropoiesis

Produced by increased erythropoietin production results from tissue hypoxia caused by such diverse factors as detective high oxygen affinity type of hemoglobin, anemia, chronic lung disease, inappropriate erythropoietin production

Secondary Polycythemia

Common cause of secondary erythrocytosis

Smoking

Primary cause of higher erythropoietin is?

Secondary Polycythemia

An autosomal dominant trait that produces a defect in the regulation of erythropoietin

Familial Polycythemia

Methods of EPO Determination: Like pregnancy test, use of lab animals

Bioassays

Methods of EPO determination: Ag-ab reactions, monoclonal ab

Immunologic Assays

- Aplastic Anemia - Decrease clearance of EPO - Panmyelophthesis

Increased EPO

- Increase clearance EPO - Very high RBC count - Increase oxygen carrying capacity

Decreased EPO

Bone marrow failure

Aplastic Anemia

Example of Decreased EPO: Kidney Damage

Chronic Kidney Disease (CKD)

- Normal RBC Production - Synchronous Maturation

Normoblastic Maturation

Macrophages surrounded by developing normoblast. Macrophages salvages iron and supply it to the developing normoblast

Erythroblastic Island

- Nurse Cells - Supplies iron to the developing pronormoblast

Macrophage

Stage it commences - basophilic normoblast stage up to reticulocyte stage

Hemoglobinization

Heme synthesis happens in the?

Mitochondria

Globin synthesis happens in the?

Ribosomes

Pyknosis and nuclear extrusion giving rise to reticulocyte

Orthochromatic Stage

Erythrocytes Maturation: Release in the circulation - retics - after _____

1-2 days

- Abnormal Maturation - Asynchronous Maturation

Megaloblastic Maturation

Nuclear maturation lags behind cytoplasmic maturation

Asynchronous Maturation

Causes: Vit B12 deficiency, Folic Acid Deficiency, Malabsorption, Lack of IF, Infection

Megaloblastic Maturation

Essential requirement for nuclear development:

Vitamin B12 deficiency, Folic Acid Deficiency

Problems affecting Vitamin B12 Absorption

Malabsorption, Lack of IF, Infection

Bacteria that can cause stomach ulcer

Helicobacter Pylori

Fish Tapeworm Infection, Parasitic

D. Latum

Abnormally large pronormoblast

Megaloblast

Nuclear Fragmentation

Karyorrhexis

Abnormally large blood cells

Macrocyte

- Abnormal RBC - Inclusion composed of DNA

Howell Jolly bodies

Blood Structure and Function:

Diameter: 6-8 um

Erythrocyte Structure: 1/3 of the cell diameter

Central Pallor

Primary function is to transport O2 from lungs to tissues

Red Blood Cells

- RBC Membranes Proteins: Lipids: Carbohydrates:

50%, 40%, 10%

- Transport substances - Links lipids membrane to cytoskeletal proteins - Transport sites, adhesion site, signaling receptors - Ankyrin complex

Transmembrane/Integral Proteins

Ankyrin Complex:

Band 3, Glut 1, Glycopherin A (Sialic Acid), Protein

Anion transport

Band 3

Glucose Transport

Glut 1

- Sialic Acid - Zeta Potential (negative charge)

Glycopherin A

Ratio of Protein

4:1

Main cytoskeletal proteins:

Spectrin

Two types of Spectrin:

Alpha Spectrin, Beta Spectrin

Shape and Flexibility - Actin Junction Complex

Cytoskeletal/Peripheral Proteins

Provides membrane structural integrity

Actin Junctional Complex

Maintaining the horizontal & ventral structure of RBC

Band 3, Protein 4.1, 4.2, Spectrin, Actin

40% Lipids is composed of

Phospholipid Bilayer

Phospholipid outer layer:

Phosphatidyl/Choline & Sphingomyelin

Phospholipid inner layer:

Phosphatidyl/Serine & Phosphatidyl Ethaholamine

Selective entry of substances into RBCs

RBC Permeability

Does not allow Na, K, Ca to enter the RBC

Impermeable

It allows water, bicarbonate and chloride to enter the RBC

Permeable

In ATP dependent cation pumps, it has two defect

Cell Swelling, Cell Shrinkage

Maintains the RBC intracellular & extracellular cation

Na-K AtPase

In RBC Intracellular and Extracellular Cation, the Primary IC of Potassium has a ratio of?

25:1

In RBC Intracellular and Extracellular Cation, the Primary EC of Sodium has a ratio of?

1:12

Metabolic Pathway

Embden-Meyerhof Pathway (EMP), Hexose Monosphate Shunt (HMS) / Penrose Phosphate Pathway (PPP), Luebering-Kapoport Pathway (LKP), Methemoglobin Reductase Pathway (MRP)

In this type of pathway the RBC lacks mitochondria and nucleus. It contains hemoglobin only.

Embden-Meyerhof Pathway

- Anaerobic Glycolysis - Produce 2 mol of ATP - A source of ATP Requirement which composed of 90-95% - Support three metabolic pathways

Embden-Meyerhof Pathway

- Cell rigidity and decrease survival - Affecting shape and flexibility of RBC it became rigid

Lower level of ATP

The plasma glucose

Glycolysis

Maintain cell membrane structure and intracellular substances

ATP

5-10% of energy requirement

Hexose Monosphate Shunt

In Hexose Monosphate Shunt, what is the oxidize form of glutathione

GSSG

In Hexose Monosphate Shunt, what is the reduced form of glutathione?

GSH

Prevents hemoglobin denaturation

GSH

To protect and preserve hemoglobin you need to reduced the?

GSH

Abnormal RBC inclusion composed by hemoglobin

Heinz Bodies

During megaloblastic maturation we have what type of DNA?

Howell Jolly Bodies

Product of Emden-Meyerhof Pathway?

ATP

Product of Hexose Monophosphate Pathway

GSH

Produce: 2,3 DPG - regulate hemoglobin affinity to O2

Luebering-Kapoport Pathway

The role of this pathway is to make sure that the iron will remain in ferrous state by preventing the oxidation of ferrous iron to ferric iron

Methemoglobin Reductase Pathway

The iron is in the what type of state? Which is functional and capable of transporting oxygen.

Fe2+ (Ferrous State)

The hemoglobin's iron is in the what type of state? If the hemoglobin is non-functional and incapable of transporting oxygen.

Fe3+ (Ferric State)

The methemoglobin reductase is also called?

Cytochrome B5 Reductase

100

Mechanism of RBC Production

Fragmentation, Osmotic Lysis, Erythrophagocytosis, Splenic Spitting, Splenic Culling, Complement, Hgb Denaturation

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