Chapter 42 TBL

What is another name for platelets? 

**Thrombocytes**

What is the primary function of platelets?

**Clotting**

Where are blood cells produced?

**Bone Marrow**

What cell is the progenitor of all blood cells?

**Hematopoietic stem cells**

What stimulates production of leukocytes?

**Infection**

Decreased oxygen supply in the tissue results in  _______  production in what organ?

**Erythropoietin production in kidney**

How is NAD+ regenerated in erythrocytes?

**Lactate Dehydrogenase**

What is methemoglobin?

**Ferric oxidized form of hemoglobin**

What cofactor is used to reduce methemoglobin?  What pathway does it come from?

**Cytochrome B5; Glycolysis**

What is the function of 2,3 bisphosphoglycerate?

**2,3-BPG is a modulator of oxygen binding to hemoglobin that stabilizes the deoxy form of hemoglobin, facilitating the release of oxygen to the tissues**

How is 2,3 bisphosphoglycerate produced?

**Rapoport-luebering shunt**

Besides ATP and NADH, what is the metabolic product of glycolysis?

**Pyruvate**

Name the 3 types of granulocytes.  Besides granules, what morphology do they share?

**Neutrophils, Basophils, Eosinophils. They share segmented nuclei**

Name two blood cell types that lack nuclei?

**Erythrocytes & Thrombocytes (RBC’s and platelets)**

Eosinophilic granules are ______?

Lysosomes (contain hydrolytic enzymes and cationic proteins, toxic to parasitic worms)

Which blood cells have a high ratio of nuclear to cytoplasmic volume?

Lymphocytes

Which leukocytes participate in hypersensitivity reactions?

Basophils (Granulocyte)

Name the 3 major types of lymphocytes?

T-Cells (Thymus-derived lymphocytes), B-Cells, NK Cells

How is histamine produced?  In which cells?  From what precursor?  What is the reaction?

\`Produced by the decarboxylation of histidine

Stored in secretory granules of basophils

Hypersensitivity reaction, such as allergic responses

Which leukocytes contain secretory granules?

Granulocytes

Lymphocytes precursors of ______ migrate from the bone marrow to _____ ?

T-cells; thymus

Which lymphocyte mature in the bone marrow?

B-cells

What are the precursors of tissue macrophages?

Circulatory monocytes

Release of histamine during basophil activation causes  ______  and results in _______.

Smooth muscle contraction; increased permeability

Name 3 other compounds in basophilic granules.

Proteases, ß-glucuronidase, and lysophospholipase

What are 2 functions of the contents of basophilic granules?

Degrade microbial structures and assist in remodeling of damaged tissue

Which cells secrete antibodies? In response to what?

B-cells; In response to antigen binding

Which cells consume necrotic tissue debris?

Monocytes

Which cells target virus-infected and malignant cells for destruction?

Cytotoxic T cells

Which cells remove erythrocytes? In what organ?  Why are some erythrocytes removed?

Macrophages in the liver and spleen. Some erythrocytes are removed when they have irregular shape or have inclusion bodies.

Besides carrying oxygen, what other function is provided by erythrocytes?

Transport oxygen to tissues and contribute to buffering through hemoglobin binding protons.

What is the precursor cell of platelets?

Megakaryocytes

What blood measure is used to determine if a patient is anemic?

Hematocrit

Name three causes of hypochromic microcytic anemia.

Iron deficiency, lead poisoning, thalassemia mutation

The functional defect in hypochromic microcytic anemia is impaired _______ ________.

impaired hemoglobin synthesis

Normocytic normochromic anemia is most likely caused by which 3 things?

Acute bleeding, sickle cell disease, red blood cell metabolic defects/membrane defects

The ATP produced by erythrocytes is used mainly for what 3 things?

Ion transport across the cell membrane (Na+, K+, and   Ca2+)

Phosphorylation of membrane proteins

Priming reactions of glycolysis

The Rapoport-Leubering shunt of glycolysis is used to produce _______.

2,3 BPG

What effect does 2,3 BPG have on hemoglobin?

a modulator of oxygen binding to hemoglobin that stabilizes the deoxy form of hemoglobin, facilitating the release of oxygen to the tissues

What is the physiological consequence of 2,3 BPG?

increases O2 release to tissues that need it

What is the name of the system that reduces methemoglobin?

NADH-cytochrome b5 – methemoglobin reductase system

What is a pyrrole ring?

A ring composed of 4 carbons and 1 nitrogen - 4 pyrrole rings make up porphyrin ring which binds iron to form heme.

Describe a porphyrin ring.

**The ring contains a Fe2+ ion in the center with 4 pyrrole rings joined by methylene bridges.**

**It has 8 side chains, 2 per pyrrole and four nitrogens on the inside of the ring.**

The side chains on the heme porphyrin ring are composed of which 3 groups?

**Acetate**

**Propionate**

**Methyl or vinyl**

Names 3 (or 4) substances in the human body that contain heme.

**Hemoglobin**

**Myoglobin**

**Cytochromes**

What are the precursors of the first reaction of heme synthesis?

**Pyridoxine - Vitamin B6**

The products of the first reaction of heme synthesis forms _________, ________ and _____ ?

**Glycine, Succinyl-CoA, Vit B6**

What does the amino group on heme come from?  Where does the energy come from?

**Glycine, NADPH**

Where does the carbon dioxide on heme come from?

Comes from **glycine**

What is the name of the enzyme that catalyzes the first reaction of heme synthesis?  What cofactor is required?

**Delta-aminolevlinic acid synthase**

Cofactor - **pyridoxal phosphate**

Which vitamin deficiencies are often associated with macrocytic, normochromic anemias?

**Vitamin B12 , Folate**

The second reaction of heme synthesis involves the condensation of 2  _____ to form   _________.

**Aminolevlinic** to form **Porphobiliogen**

What is the name of the enzyme that catalyzes the second reaction of heme synthesis?

**delta-Aminolevulinic acid dehydratase**

What is a porphyrinogen?  What side chains are present on the first porphyrinogen in heme synthesis?

**Porphyrinogen are intermediates in the biosynthesis of porphyrins.**

**Farnesyl-pyrophosphate**

Protoporphyrin IX is formed by oxidation of ________.

**The methylene by Protoporphyrinogen oxidase**

The enzyme that adds iron to Protoporphyrin IX is called ______.

**Ferrochelatase**

Which is more easily absorbed: iron from plants or heme iron from meats?

**Iron from meats is more easily absorbed, because plants contain oxalates**

What vitamin increases the uptake of non-heme iron from the digestive tract?

Vitamin C

What is a porphyria?

A defect in any stage heme of synthesis leading to multiple diseases

What is the name given to a total lack of Hb A?  Is this compatible with life?

Alpha Thalassemia; No

Iron is absorbed by the intestine in what state?

Iron is absorbed by the intestine in the ferrous state (Fe+2).

What state is iron transported in?

In a Ferric State

What is the name of the enzyme that makes the conversion of iron to the transported form?

Ferroxidase/ceruloplasmin

What metal is contained in the enzyme that converts iron to the transported form?

Copper (Cu2+)

Iron is transported on a protein carrier called  ____.

Transferrin

The total iron binding capacity is usually higher than the amount bound to iron by how much?

Total iron binding capacity is greater by about 200

How is iron transported from blood into cells?

Transferrin binds to iron then binds to transferrin receptors on the surface of cells. The complex gets internalized into the cell. The internalized membrane develops into an endosome, and the iron is reduced by a membrane-bound oxidoreductase. Ferrous transported out of the endosome into the cytoplasm via DMT-1

Where is the intracellular iron converted to the ferrous state?

Through an endosome

What enzyme reduces the intracellular iron?

Oxidioreductase

The ferrous iron is transported out of the endosome by _______ ?

DMT-1

What happens to the intracellular Fe2+ that is not immediately incorporated into heme or enzymes?

Oxidized and bound to ferritin for storage

Most of the body’s iron storage is in what 3 locations?

liver, spleen, and bone marrow

Excess iron is stored as _____, which is _______ combined with additional iron.

Hemosiderin, ferritin

Heme synthesis is regulated by controlling the activity of which enzyme?

δ-ALA synthase

______ is an allosteric negative regulator of heme synthesis.

**HEME**

Heme represses synthesis of what enzyme?

**Delta Aminolevunic acid**

How does heme regulate globin synthesis?

**Maintains rediculocyte ribosome initiation complex in active state. (Inhibits phosphorylation and inactivation of eIF2)**

What happens to globin after erythrocytes are phagocytized?

**Globin is cleaved into constituent amino acids**

What happens to heme in the phagocytes? What are the products of this reaction?

**Heme is degraded to bilirubin, CO2, and Fe2+.**

Name the enzyme that cleaves heme and releases iron.

**HEME OXYGENASE**

Explain the difference between biliverdin and bilirubin.

**Biliverdin is a bisected open chain heme connected by a methylene bridge. Bilirubin is the reduced form of Biliverdin (middle methylene bridge reduced)**

What cofactor and enzyme is required to convert biliverdin to bilirubin?

**NADPH is used with Biliverdin Reductase to convert biliverdin to bilirubin**

What is used to increase the solubility of bilirubin?

**Bilirubin is conjugated with glucuronide molecules to increase its solubility**

To what group in bilirubin is glucuronic acid added?

**The propionate groups in the middle of the bilirubin molecules**

How does conjugated bilirubin get from the liver to the intestines?

**After being conjugated to bilirubin diglucuronide the liver excretes the molecule into the bile which travels to the gallbladder, and is eventually released into the intestines**

Bacteria in the large intestine convert deconjugated bilirubin to?

**Deconjugates and converts bilirubin into urobilinogens**

How do RBCS that are 7.5 micron diameter traverse spleen passages of only 3 micron diameter?

**Compression/deformation of membrane**

What allows RBC to be deformed?

**Cytoskeleton - spectrin**

Name the 5 proteins that form the RBC cytoskeleton.

**Spectrin, ankyrin, Band 4.1, Band 4.2, Band 3, actin**

What are the 2 integral membrane proteins that bind to cytoskeletal proteins? 

**Actin, ankyrin**

Which protein is the major cytoskeletal protein?  Why?

**Spectrin - gives membrane flexibility**

What does ankyrin bind to?

**Spectrin a/b, Band 3, glycophorin A**

What does actin bind to?

**Spectrin, glycophorin C, Band 4.1**

What does spectrin bind to?

**Actin, Band 4.1, ankyrin**

What does band 4.1 bind to?  

**Actin, spectrin, glycophorin C**

Which one protein provides the most motion during RBC deformation?

**spectrin**

What is SOCS? What does it do?

***S*****ilencer** ***O*****f** ***C*****ytokine - inhibits STAT dimerization and signal transduction OR JAK phosphorylation, activation of STAT**

Most hematopoietic growth factors recognize receptors in the _______ family.

**Cytokine JAK/STAT transducer**

The hematopoietic growth factors receptors use ____ and ____ to transduce their signal?

**JAKs and STATs**

Thalassemias usually result from uneven ratios of what polypeptides?

**a/b globins**