Ppt Flashcards by Kyra Catedral

ERYTHROCYTE
• FUNCTION:
• 1ST;
• 2ND :

To carry oxygen from lungs to the tissue

Returning carbon dioxide
to the lungs

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(RBC precursor)

Aka:

Erythroblast

Normoblast

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• Developing nucleated RBC precursor with normal appearance

•Restricted to the_____

• Erythroblast (RBC precursor)
Aka: Normoblast

bone marrow

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3 Erythroblast Nomenclature

• NORMOBLASTIC TERMINOLOGY
• RUBRIBLASTIC TERMINOLOGY
• ERYTHROBLAST TERMINOLOGY

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Normoblastic

Pronormoblast

Basophilic normoblast

Polychromatic (polychromatophilic) normoblast

Orthochromic normoblast

Polychromatic (polychromatophilic) erythrocyte

Erythrocyte

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Rubriblastic

Rubriblast

Prorubricyte

Rubricyte

Metarubricyte

Polychromatic (polychromatophilic) erythrocyte*

Erythrocyte

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Erythroblastic

Proerythroblast

Basophilic erythroblast

Polychromatic (polychromatophilic) erythroblast

Orthochromic erythroblast

Polychromatic (polychromatophilic) erythrocyte*

Erythrocyte

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2 PROGENITOR:

• BFU-E (Burst-forming unit-erythroid)

• CFU-E (Colony forming unit-erythroid)

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• Earliest committed progenitor
• Gives rise to large colonies

BFU-E (Burst-forming unit-erythroid)

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• Capable of multisubunit colonies (burst)

BFU E

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• Gives rise to smaller colonies

CFU-E (Colony forming unit-erythroid)

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1st morphologically Identifiable RBC precusor

PRONORMOBLAST

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: to produce MATURE RBC from BFU-E

• 18-21 days

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STAGES OF ERYTHROID PRECURSOR MATURATION

Over all diameter of the cell decreases
Diameter of the nucleus decreases more rapidly than the diameter of the cell
Nuclear chromatin pattern becomes coarser, clumped and condensed
Nuclei Disappear
Cytoplasm changes from blue to gray-blue to salmon pink

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ERYTHROKINETICS

STIMULUS OF RBC PRODUCTION

HYPOXIA

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• Primary oxygen-sensing system

Kidney(Peritubular Fibroblast)

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• Consist of a carbohydrate unit and termina sialic acid unit

• EPO (ERYTHROPOIETIN)

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• Thermostable, nondialyzeble, glycoportein hormone

EPO (ERYTHROPOIETIN)

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• Major stimulatory cytokine for RBC

EPO (ERYTHROPOIETIN)

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EPO (ERYTHROPOIETIN)

Consist of a______ unit and termina_____ unit

carbohydrate

sialic acid

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• ACTION of ERYTHROPOIETIN
• Growth factor (cytokine) that initiates intracellular message to developing
erythroid cells =_________

SIGNAL TRANSDUCTION

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= increased cell division and maturation, increased intestinal iron absorption and hemoglobin synthesis and more RBCs entering the circulation

• EPO + EPOR

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EPO (ERYTHROPOIETIN)
• 3 MAJOR EFFECTS:

Allowing early release of reticulocytes from the bone
marrow
Preventing apoptotic cell death
Reducing the time needed for cells to mature in the bone marrow.

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THERAPEUTIC USES OF EPO
• Produced by recombinant technology-______ and _______

EPOITIN alpha & EPOITIN beta

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THERAPEUTIC USES OF EPO

• Stimulates RBC proliferation and differentiation by acting to specific receptors in the BM • Anemias of chronic infection • Anemias resulting from chemotherapy • Anemias secondary to malignancy; associated with HIV • Anemias in premature infants • Autologous blood transfusion; After BM transplant

IRON • No mechanism for_____ • Just minimal daily loss with….

active excretion exfoliated skin and hair and sloughed intestinal epithelia.

• The body stores iron • Percentage of body iron • 70%- held within_____ • 20%- in_____ • 10%- divided among the….

hemoglobin storage muscles, the cytochrome, various iron-containing enzymes and the plasma

Functional Compartment ______in the blood ______in muscles (4) enzymes in all cells

Hemoglobin iron Myoglobin iron Peroxidase, catalase, cytochromes, riboflavin

Storage compartment _______ and ______mostly in macrophages and hepatocytes; small amounts in all cells except mature red blood cells

Ferritin and hemosiderin

Transport compartment ______in plasma

Transferrin

IRON In cells, ferrous iron can react with peroxide via________, forming highly reactive oxygen molecule

Fenton Reaction

- complex and capable of generating both hydroxyl radicals and higher oxidation states of the iron

•FENTON REACTION

• Able to damage proteins, Lipids and nucleic acids

Free radicals

Short lived but potent oxidizing agent

• HYDROXYL RADICAL (OH) • AKA: FREE RADICALS

Most dietary iron is nonheme ionic iron in the______ form and must be REDUCED by_____

FERRIC FORM duodenal cytochrome b (Dcytb)

REDUCED FORM-carried across the luminal side of the enterocyte by

DMT1 divalent metal transporter 1 (DMT1)

• Ferric iron can be stored as_____

FERRITIN

ONLY known protein that exports iron across cell membrane

• FERROPORTIN

• Exports ferrous iron into the blood

• FERROPORTIN

• Protein on basolaminal side of enterocyte

• FERROPORTIN

• Secreted by hepatocytes • Protein that able to bind to receptor ferroportin

HEPCIDINE

IRON TRANSPORT IN THE BLOOD State of iron- for transport in the blood

• Ferrous to Ferric

Protein on the basolaminal enterocyte membrane • Able to oxidized iron as it exits the enterocyte

HEPHAESTIN

• OXIDIZED IRON-carried by _____ Once the iron binds, the molecule is known as______

apotransferrin (ApoTF) TRANSFERRIN

• ApoTF - binds to 2 molecule of ferric iron

Differic transferrin or holotransferrin

REGULATION OF BODY IRON

• Proteins involved: • Transferrin 1 (TfR1) • Hemochromatosis receptor (HFE) • TfR2 • Hemojuvelin (HJV) • Bone morphogenic protein (BMP) • Receptor: BMPR • Sons of mother against decapentaplegic(SMAD) • Matriptase 2

Binds circulating diferric transferrin and releases hemochromatosis protein (HFE) for signaling

Transferrin receptor 1 (TfR1)

With transferrin receptor 2, associates with bone morphogenetic protein receptor (BMPR) to initiate the signal to upregulate hepcidin production

Hemochromatosis protein (HFE)

With transferrin receptor 2, associates with bone morphogenetic protein receptor (BMPR) to initiate the signal to upregulate hepcidin production

Hemochromatosis protein (HFE)

With freed HFE, associates with BMPR to initiate the signal to upregulate hepcidin production

Transferrin receptor 2 (TfR2)

The ligand that initiates signal transduction when it binds to its receptor in a cell membrane

Bone morphogenetic protein (BMP)

A common membrane receptor initiating signal transduction within a cell when its ligand (BMP) binds

Bone morphogenetic protein receptor (BMPR)

A coreceptor acting with BMPR for signal transduction, leading to hepcidin production

Hemojuvelin (HJV)

A second messenger of signal transduction, phosphorylated by BMPR-HJV complex, and able to migrate to the nucleus and upregulate hepcidin gene expression

Sons of mothers against decapentaplegic (SMAD)

Cleaves hemojuvelin to downregulate hepcidin production

Matriptase-2

Binds holotransferrin (Tf), which initiates a signal leading to secretion of erythroferrone

Transferrin receptor 2 (TfR2)

Able to downregulate hepcidin production in the liver: mechanism unknown

Erythroferrone (ERFE)

Ferric Iron is stored in a cage-like protein_____.

apoferritin

- once iron binds • 1 ferritin molecule - can bind ______ iron ions •______- partially degraded ferritin

FERRITIN >4000 HEMOSIDERIN

• Control the amount of_____ • To avoid free radicals

TfR1

• STORED IRON: • SUFFICIENT-TfR1 production declines =_______ • LOW - TfR1 production increases =_______

REDUCING ION ABSORPTION TO AQUIRE MORE IRON

Foods containing high levels of iron:

Red meat legumes dark green leafy vegetables

Iron may not be readily absorbed and thus is NOT

BIOAVAILABLE

• Iron can be absorbed as either_______ or _______ form of heme

IONIC IRON (Ferrous form) or NONIONIC IRON (Ferric form)

• _____ form - absorption into enterocyte via DMT1

Fe2

_______ form • From plant sources • Not readily absorbed

Fe2 form

Dietary compounds can bind iron and inhibits absorption Release from these binders and reduction to ferrous form are enhanced by gastric acid, acid foods (e.g. Citrus) and an enterocyte luminal membrane ferrireductase and Dcytb

Oxalates phytates phosphates calcium