Ppt Flashcards
ERYTHROCYTE
• FUNCTION:
• 1ST;
• 2ND :
To carry oxygen from lungs to the tissue
Returning carbon dioxide
to the lungs
(RBC precursor)
Aka:
Erythroblast
Normoblast
• Developing nucleated RBC precursor with normal appearance
•Restricted to the_____
• Erythroblast (RBC precursor)
Aka: Normoblast
bone marrow
3 Erythroblast Nomenclature
• NORMOBLASTIC TERMINOLOGY
• RUBRIBLASTIC TERMINOLOGY
• ERYTHROBLAST TERMINOLOGY
Normoblastic
Pronormoblast
Basophilic normoblast
Polychromatic (polychromatophilic) normoblast
Orthochromic normoblast
Polychromatic (polychromatophilic) erythrocyte
Erythrocyte
Rubriblastic
Rubriblast
Prorubricyte
Rubricyte
Metarubricyte
Polychromatic (polychromatophilic) erythrocyte*
Erythrocyte
Erythroblastic
Proerythroblast
Basophilic erythroblast
Polychromatic (polychromatophilic) erythroblast
Orthochromic erythroblast
Polychromatic (polychromatophilic) erythrocyte*
Erythrocyte
2 PROGENITOR:
• BFU-E (Burst-forming unit-erythroid)
• CFU-E (Colony forming unit-erythroid)
• Earliest committed progenitor
• Gives rise to large colonies
BFU-E (Burst-forming unit-erythroid)
• Capable of multisubunit colonies (burst)
BFU E
• Gives rise to smaller colonies
CFU-E (Colony forming unit-erythroid)
1st morphologically Identifiable RBC precusor
PRONORMOBLAST
: to produce MATURE RBC from BFU-E
• 18-21 days
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
ERYTHROKINETICS
STIMULUS OF RBC PRODUCTION
HYPOXIA
• Primary oxygen-sensing system
Kidney(Peritubular Fibroblast)
• Consist of a carbohydrate unit and termina sialic acid unit
• EPO (ERYTHROPOIETIN)
• Thermostable, nondialyzeble, glycoportein hormone
EPO (ERYTHROPOIETIN)
• Major stimulatory cytokine for RBC
EPO (ERYTHROPOIETIN)
EPO (ERYTHROPOIETIN)
Consist of a______ unit and termina_____ unit
carbohydrate
sialic acid
• ACTION of ERYTHROPOIETIN
• Growth factor (cytokine) that initiates intracellular message to developing
erythroid cells =_________
SIGNAL TRANSDUCTION
= increased cell division and maturation, increased intestinal iron absorption and hemoglobin synthesis and more RBCs entering the circulation
• EPO + EPOR
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.
THERAPEUTIC USES OF EPO
• Produced by recombinant technology-______ and _______
EPOITIN alpha & EPOITIN beta
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
