LIVER AND BONE MARROW 1. Glycine + Succ CoA = D-ALA >> PORPHOBILINOGEN (PBG) 2. Four porphobilinogens = PORPHYRIN 3. Porphyrin + Fe2 = HEME NEEDS FOLIC ACID AND ZINC

Heme Flashcards by Brianna Spahn

A bone marrow stem cell that has the potential to become any blood cell

Hematocytoblast ( >myelobast or >lymphoblast)

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Monoblast

Monocyte/Macrophage

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WBC to RBC precursors in bone marrow

3:1

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Main growth factor for erythrocytes.

Increases 1000 fold in presence of hypoxia

Erythropoietin

peptide hormone, produced in kidneys by peritubular capillary cells

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Main growth factor for thromboblasts

Thrombopoietin

Also GM-CSF and Interleukins

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Main growth factors for myeloblasts

G-CSF (Granulocytes only!)
GM-CSF (granulo + mono + erythro)
IL-3

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7 day process of making an RBC

Hematocytoblast > (EPO) > 
Erythroblast > (EPO, GM-CSF) >
NRBC > (loose nucleus) >
Retic > (enter circulation, lose ribosomes) >
Eryth

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Hemoglobin, chains

1/3 mass of RBC

2 alpha chains, 2 beta chains

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95% of adults hemoglobin

A1 (Alpha 2, Beta 2)

α2β2

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1.5-3.5% adults hemoglobin

A2 (alpha 2, Delta 2)

α2δ2

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Fetal Hemoglobin

F (α2γ2)

Can be elevated in sickle cell or beta thalassemia

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Large chemical group called a PORPHYRIN, made of 4 rings attached to a central iron ion

Heme

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Other uses for Heme

Myoglobin
Nitric Oxide Synthesis
Cytochromes (mitochondria, smooth ER)
Catalase

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Heme synthesis

LIVER AND BONE MARROW

Glycine + Succ CoA = D-ALA»_space; PORPHOBILINOGEN (PBG)
Four porphobilinogens = PORPHYRIN
Porphyrin + Fe2 = HEME

NEEDS FOLIC ACID AND ZINC

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Inherited disorder of heme production

Muscular disorders / pain
Tooth changes
Increased hair growth
Sun intolerance
Personality changes
Neuropathies

Porphyria

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IRON -
absorbed in___ by___
Stored as ___
travels as ___

Duodenum, enterocytes
Ferritin
Transferrin

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Reticuloendothelial System

Liver
Spleen
Bone Marrow
Lymph Nodes

and their macrophages

RBC BREAKDOWN

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HEMOGLOBIN BREAKDOWN in RES

Globin»_space; amino acid recycle

Heme > Conjugate, send to liver >
> Biliverdin > Bilirubin > Bile > Urobilinogen > Feces as Stercobilin / reabsorbed recycled

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Hemoglobin α2β2, with β abnormal chains (β 6Glu-Val) which tend to change shape at lower pH and/or upon accepting O2

HbSS / HbAS

Sickle Cell

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Missing one or more of the 4 alpha globin genes

Alpha ThaLESSemia (“less” one type of globin chain)

Hemoglobin H (HbH): 
Four β chains joined together (β4)

minor = heterozygous
major = homozygous / missing all normal genes

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Missing one or both of 2 beta glob in genes

Beta ThaLESSemia

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Hemoglobin H (HbH): 
Four β chains joined together (β4)

Hemoglobin Barts (HbBarts):
Four γ chains joined together (Υ4)

Alpha ThaLESSemia Major

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Genetic Methemoglobinemia

Study These Flashcards

Defective Cytochrome B5 Reductase

HbM

Study These Flashcards

Methemoglobin (normal = 1-2% of heme at a time)

Fe3+ instead of Fe2+

Occurs in presence of oxidative stressors, normally corrected by NADH >(Ctyo B5)> NAD+

Fe3+ does not hold O2, in permanent “deoxy” shape

See cyanotic skin discoloration when HbM is

10-20%

Oxidizing chemicals that can cause methemoglobinemia

``` Nitrates Benzocaine (local anesthetic) Dapsone (antibiotic) Prilocaine (local anesthetic) Trimethoprim, sulfa drugs ```

Glycolysis pathway in RBC

Emden Myerhoff Pathway GLUCOSE ONLY NET: 2 ATP, 2 LACTATE MOLECULES FOR EVERY GLUCOSE MOLECULE 1. Invest 2 ATP 2. G6PD 3. First "payoff" 2 ATP 3. NADH > NAD+ 4. Pyruvate 5. Second "payoff" 2 ATP

G6PD detour - follows this pathway instead of glycolysis Generates NADH ** for RBCs (no mitochondria)

Hexose Monophosphate Shunt G6PD makes NADH > NADH refuels Glutathione > DETOX

How NADH works to decrease oxidative stress

Refuels GLUTATHIONE (which detoxes oxidized molecule)

G6PD Deficiency

**Most common enzyme deficiency in the world** X LINKED Can't produce NADH via HMP shunt (for RBCs) HEMOLYTIC ANEMIA RESULTS

G6PD Deficiency Triggers

``` Drugs Infections Fava Beans Diabetic Ketoacidosis Some chemicals (moth balls, methylene blue, HENNA) ``` **MAY PROTECT AGAINST MALARIA**

Platelet Lifespan and Growth Factors

10 days GM - CSF Interleukins 3, 6, 11

Dysfunctional stem cell lines in bone marrow. Precursor to AML. Requires bone marrow transplant

Myelodysplastic Syndrome

Autoimmune destruction of myeloid elements in peripheral blood by out-of-control macrophages. Bone marrow liver and spleen show macrophages that have eaten up all the RBCs. Decrease in all myelocytic lines, hepatosplenomegaly, anemia

Idiopathic Pancytopenia aka Hemophagocytic Syndrome

Total dysfunction of bone marrow stem cells. Bone marrow biopsy will show significant decrease ins ten cells, replaced by fat.

Aplastic Anemia (Idiopathic, chemo, drugs, viruses

Trifecta of Hemostasis

Vasoconstriction Platelet Aggregation Stasis

What causes vasoconstriction in the platelet aggregation pathway?

Thromboxane A2 (TXA2) Exposed collagen of endothelium triggers platelets to aggregate and produce TXA2, which directly causes vasoconstriction LOCALLY at the site of injury

How is TXA2 localized?

Endothelial cells around the clot produce PGI2 (also from arachinodic acid) which counteracts TXA2

How does aspirin help prevent heart attacks?

Inhibits the COX 1 enzyme in platelets, which decreases TXA2, and thus decreases vasoconstriction and platelet aggregation

Extrinsic vs Intrinsic Pathway

Extrinsic is more common, requires damage to endothelium (Tissue Factor) - starts at VII **MEASURED w PT/INR** **Extrinsic requires something Extra (TF)* Intrinsic is "Contact Activation" - starts at XII **MEASURED w PTT**

Intrinsic Pathway Heparin - PTT

XII > XI > IX > (VIII) > X > (V) > II > I 12 > 11 > 9 > (8) > 10 > (5) > 2 > 1

Extrinsic Pathway Warfarin / Coumadin - PT /INR

VII > IX > (VIII) > X > (V) > II > I 7 > 9 > (8) > 10 > (5) > 2 > 1

Genetic disorder characterized by deficiency in clotting factors, usually VIII

Hemophilia

PT / INR measures

EXTRINSIC PATHWAY WARFARIN / COUMADIN Vitamin K deficiency *** NOT IX

PTT measures

INTRINSIC PATHWAY HEPARIN GOOD FOR CHECKING VIII

Vitamin K Dependent Factors

II VII IX X

Common genetic factor deficiencies

Hemophilia A (VIII) Von Willebrands (vWF)

X-linked trait, usually diagnosed by 3 yrs age Trait: Bleeding into joint spaces after benign injury

Hemophilia A (VIII)

Autosomal, most common inherited bleeding disorder Bleeding gums, nosebleeds, menorrhagia

Von Willebrands vWF >> carries VIII

Unbound thrombin inactivated by

Antithrombin III | Protein C

Natural Heparin

Within granules of mast cells / basophils / surface of endothelial cells Enhances Antihrombin III and inhibits Intrinsic Pathway

Turns off amplification activity of V and VIII

Protein C **needs Protein S to function**

When Factor V can't be controlled by Protein C

Factor V Leiden Mutation Diagnose w RVV test (Russel Viper Venom)

Virchow's Triad

Stasis Endothelial Injury Hypercoagulability

Clot Buster

Plasminogen TPA (Tissue Plasminogen Activator)

Heme Flashcards

(55 cards)