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Biochemistry Chapter 44 - The Biochemistry of Erythrocytes and Other Blood Cells
Terms in this set (87)
The platelets (_______1_________), which contain cytoplasmic ________2________ but no ____3_____, are involved in the control of bleeding by contributing to normal thrombus (clot) formation within the lumen of the blood vessel.
Red blood cells lose all internal _______________ during the process of differentiation.
The mononuclear leukocyte has a ____1_____ nucleus, whereas the polymorphonuclear leukocytes have a _____2_______ nucleus.
Why are granulocytes called granulocytes, and give examples (3).
The granulocytes, so named because of the presence of secretory granules visible on staining, are the neutrophils, eosinophils, and basophils.
The granulocytes, in addition to displaying segmented nuclei (are ___________1____________), can be distinguished from each other by their staining properties (caused by different granular contents) in standard hematologic blood smears: neutrophils stain ___2_____, eosinophils stain ___3____, and basophils stain ___4____.
The mononuclear leukocytes consist of various clases of ____________ and the ______________
Lymphocytes and the monocytes
What are lymphocytes and what are the three main types?
Lymphocytes are small, round cells that have a high ratio of nuclear volume to cytoplasmic volume and are the primary antigen (foreign body)-recognizing cells.
3. NK cells
What is the function of NK cells?
To target virally infected and malignant cells for destruction.
What are the macrophages?
Macrophages are derived from the circulatory monocytes; they are phagocytic cells that enter inflammatory sites and consume microorganisms, and necrotic host cell debris left behind by granulocyte attack of the foreign material.
What is the function of Macrophages in spleen?
Macrophages in the spleen play an important role in maintainng the oxygen-delivering capabilities of the blood by removing damaged red blood cells that have a reduced oxygen-carrying capacity.
Platelets arise by budding of the cytoplasm of ________________________, multinucleated cells that reside in the bone marrow.
Normal hemoglobin level for adult male
13.5 - 17.5 g/dL
Normal hemoglobin level for adult female
11.5 - 15.5 g/dL
Normal hemoglobin level for a newborn
15.0 - 21.0 g/dL
Normal hemoglobin level for an infant 3-12 months
9.5 - 12.5 g/dL
Normal hemoglobin level for a child 1 year - puberty
11.0 - 13.5 g/dL
Normally sized RBCs
Small sized RBCs
Large sized RBCs
Cells containing a normal hemoglobin concentration are termed ________1__________; those with decreased concentration are ___________2__________.
Microcytic, hypochromic RBCs. Functional deficit: _______, Possible Causes: _____________.
Functional deficit: impaired hemoglobin synthesis
Possible Causes: iron defciency, mutation leading to thalassemia, lead poisoning
Macrocytic, normochromic RBCs. Functional deficit: _______, Possible Causes: _____________.
Functional deficit: impaired DNA synthesis
Possible Causes: Vitamin B12 or folic acid defciency, erythroleukemia
Normocytic, normochromic RBCs. Functional deficit: _______, Possible Causes: _____________.
Functional deficit: Red cell loss
Possible Causes: Acute bleeding, sickle cell disease, red cell metabolic defects, red cell membrane defects
Other measurements used to classify the type of anemia present include the _________ ______1____ ___________ (_____) and the __________ ______________ _______2________ _________________ (________).
1. mean corpuscular volume (MCV)
2. mean corpuscular hemoglobin concentration (MCHC)
Normal MCV values range from ______-_____ fL.
80 to 100 fL (femtoliters = 10 to the negative 15 Liters)
Normal range for MCHC is ______-_____ g/L
32 to 37
Erythrocytes can only generate adenosine triphosphate (ATP) by _____________-
Erythrocyte glycolysis also uses the Rapoport-Luebering shunt to generate ___________________________-
To bind oxygen, the iron of hemoglobin must be in the ___1______(+__) state. Reactive oxygen species can oxidize the iron to the ferric (+3) state, producing ______2_________
1. ferrous (+2)
Approximately 5% to 10% of the glucose metabolized by red blood cells is used to generate NADPH by way of the _________ ________________ __________.
hexose monophosphate shunt
The enzyme that catalyzes the first step of the hexose monophosphate shunt is ____________________________ (_________)
glucose-6-phosphate dehydrogenase (G6PD)
An inherited deficiency in pyruvate kinase leads to ___________ ______________.
Why does deficiency in pyruvate kinase leads to hemolytic anemia?
Because the amount of adenosine triphosphate (ATP) formed from glycolysis is decreased by 50%, red blood cell ion transporters cannot function effectively. The red blood cells tend to gain Ca2+ and lose K+ and water. The water loss increases the intracellular hemoglobin concentration. With the increase in intracellular hemoglobin concentration, the internal viscosity of the cell is increased to the point that the cell becomes rigid and, therefore, more susceptible to damage by shear forces in the circulation.
How are the effects of anemia moderated?
By the twofold to threefold elevation in 2,3-bisphosphoglycerate (2,3-BPG) concentration.
Because 2,3-BPG binding to hemoglobin decreases the affinity of hemoglobin for oxygen, the red blood cells that remain in circulation are highly efficient in releasing their bound oxygen to the tissues.
__________________1_____________________deficiency is the most common enzyme deficiency in humans, probably, in part, because individuals with ____1____ deficiency are resistant to ______2______.
1. Glucose-6-phosphate dehydrogenase (G6PD)
G6PD gene is found on ____ chromosome
All known glucose-6-phosphate dehydrogenase (G6PD) variant genes contain small in-frame deletions or missense mutations. The corresponding proteins, therefore, have decreased stability or lowered activity, leading to a reduced __________________ for the red cell.
half-life or life span
Is it possible for a person to have a mutation in G6PD gene which leads to a complete absence of G6PD?
No, these mutations would be expected to result in embryonic lethality. So no mutations have been found in humans that result in complete absence of G6PD.
Heme consists of a _______1______ ring coordinated with an atom of ____2____.
Heme is the most common porphyrin found in the body. It is complexed with proteins to form ______________, _____________, and the cytochromes, including cytochrome _________
Heme is synthesized from ______1_____and _____________, which condense in the initial reaction to form _________2_________.
1. glycine and succinyl coenzyme A (succinyl-CoA)
2. delta-aminolevulinic acid (delta-ALA)
Mutation in any of the steps of the heme synthesis leads to a group of diseases known collectively as porphyrias.
Synthesis of heme schematic
Pyridoxine (vitamin B6) deficiencies are often associated with a microcytic, hypochromic anemia. Why would a B6 deficiency result in small (microcytic), pale (hypochromic) red blood cells?
In a B6 deficiency, the rate of heme production is slow because the first reaction in heme synthesis requires pyridoxal phosphate. Thus, less heme is synthesized, causing red blood cells to be small and pale. Iron stores are usually elevated.
The iron in meats is in the form of ____1______, which is readily absorbed. The non-heme iron in _____2_____ is not as readily absorbed.
______________________ increases the uptake of nonheme iron from the digestive tract.
Vitamin C (ascorbic acid)
Iron is absorbed in the ________1______ state, but is oxidized to the ferric state by a ferroxidase known as ______2________ (a copper-containing enzyme) for transport through the body.
1. ferrous (Fe2+)
Because free iron is toxic, it is usually found in the body bound to proteins. Iron is carried in the blood (as Fe3+) by the protein _______1__________, with which it forms a complex known as ______2________.
delta-Aminolevulinic acid (delta-ALA) dehydratase, which contains zinc, and ferrochelatase are inactivated by ________. Thus, in lead poisoning, delta-ALA and protoporphyrin IX accumulate, and the production of heme is decreased. Anemia results from a lack of hemoglobin, and energy production decreases because of the lack of cytochromes for the electron-transport chain.
Storage of iron occurs in most cells but especially those of the _____, ______, and _______ _________. In these cells, the storage protein, apoferritin, forms a complex with iron (Fe3+) known as ____________.
1. liver, spleen, and bone marrow
An inherited mutation in SLC11A2 (the gene encoding _________________________________________) leads to an iron deficiency anemia, as indicated by a refractory hypochromic microcytic anemia. The iron is trapped in ________________ _____________ and cannot be released to bind to ferritin, or used in other necessary biosynthetic reactions. This leads to reduced heme synthesis, reduced globin synthesis, and anemia.
1. divalent metal ion transporter 1 [DMT-1]
2. endosomal vesicles
Iron is absorbed from the diet, transported in the blood by transferrin, stored in ferritin, and used for the synthesis of cytochromes, iron-containing enzymes, hemoglobin, and myoglobin. It is lost from the body with bleeding and sloughed-off cells, sweat, urine, and feces. Hemosiderin is the protein in which excess iron is stored. Small amounts of ferritin enter the blood and can be used to measure the adequacy of iron stores. RE, reticuloendothelial.
Heme is degraded to form ___________, which is conjugated with __________ _____ and excreted in the _________.
2. glucuronic acid
Normal life span of erythrocytes
Degradation of Heme:
Heme is oxidized and cleaved to produce carbon monoxide and ______1______. ______1______ is reduced to _____2_____, which is transported to the liver complexed with serum _____3______.
What form of bilirubin is bound to albumin?
In the liver, bilirubin is converted to a more water-soluble compound by reacting with UDP-glucuronate to form bilirubin __________________, which is converted to the diglucuronide. This ______________ form of bilirubin is excreted into the bile.
In the intestine, bacteria _________1____________ bilirubin diglucuronide and convert the bilirubin to urobilinogens.
Most of the urobilinogen is oxidized to ____2____, such as stercobilin, and excreted in the feces. These pigments give feces their brown color.
Drugs, such as phenobarbital, induce enzymes of the drug- metabolizing systems of the endoplasmic reticulum that contain _______1________ _______. Because heme is used for synthesis of _________1_______ _______, free heme levels fall and _________________2_______________ synthase is induced to increase the rate of heme synthesis.
1. cytochrome P450
2. delta- aminolevulinic acid (delta-ALA)
In an iron deficiency, what characteristics will blood exhibit?
Iron deficiency will result in a microcytic, hypochromic anemia. Red blood cells will be small and pale. In contrast to a vitamin B6 deficiency, which also results in a microcytic, hypochromic anemia, iron stores are low in an iron deficiency anemia.
The red blood cell membrane must be highly deformable to allow it to travel throughout the capillary system in the body. This is because of a complex cytoskeletal structure that consists of the major proteins __________, __________, and _____________.
spectrin, ankyrin, and band 3 protein
On the cytoplasmic side of the membrane, proteins form a two-dimensional lattice that gives the red cell its flexibility. The major proteins are ______, _________, ___________, _________, and _________ .
spectrin, actin, band 4.1, band 4.2, and ankyrin.
The _______________ system protects the proteins and lipids from oxidative damage.
Defects in erythrocyte cytoskeletal proteins lead to ___________ ______________.
Binding of ___________ ______, ______________________, and _____________ __________ to hemoglobin decrease its affinity for oxygen.
hydrogen ions, 2,3-bisphosphoglycerate, and carbon dioxide
2,3-Bisphosphoglycerate (2,3-BPG) is formed in red blood cells from the glycolytic intermediate ___________________________ .
CO2 forms ________________ with the N-terminal amino groups of hemoglobin (Hb) chains. Approximately _____% of the CO2 in blood is carried to the lungs bound to Hb.
The binding of protons by hemoglobin lowers its affinity for _________, contributing to a phenomenon known as the Bohr effect. The pH of the blood decreases as it enters the tissues (and the proton concentration rises) because the CO2 produced by metabolism is converted to ___________ ________ by the reaction catalyzed by carbonic anhydrase in red blood cells.
2. carbonic acid
Leukemias, malignancies of the blood, arise when a differentiating hematopoietic cell does not complete its developmental program but remains in an _______________, ________________ state. Leukemias have been found in every hematopoietic lineage.
Cytokine signaling through the JAK/STAT pathway.
(1) Cytokine binding to receptors initiates dimerization and activation of the JAK kinase, which phosphorylates the receptor on tyrosine residues. (2) STAT proteins bind to the activated receptors and are themselves phosphorylated. (3) Phosphorylated STAT proteins dimerize, travel to the nucleus, and initiate gene transcription. (4) One family of proteins whose synthesis is stimulated by STATs is the SOCS (suppressor of cytokine signaling) family, which inhibits further activation of STAT proteins (5) by a variety of mechanisms.
In X-linked severe combined immuno-deficiency (SCID) disease, the most common form of SCID, circulating ____________1________________are not formed, and______________ are not active. The affected gene encodes the gamma-chain of the interleukin-2 receptor. Mutant receptors are unable to activate Janus kinase 3 (JAK3), and the cells are unresponsive to the cytokines that stimulate growth and differentiation.
1. T lymphocytes
2. B lymphocytes
In response to reduced tissue oxygenation, the kidney releases the hormone _____________________, which stimulates the multiplication and maturation of erythroid progenitors.
Reticulocytes still retain _______1_______ and __________________ and are capable of synthesizing _________2________.
1. ribosomes and messenger RNA (mRNA)
Reticulocytes mature in the __________, where the ribosomes and mRNA are lost
Inapropriate JAK/STAT signaling is associated with development of lymphoid and myeloid _______1_______, severe congenital _______2_______ (a condition in which levels of circulating neutrophils are severely reduced), and Fanconi anemia, which is characterized by______________3______________ ..
3. bone marrow failure and increased susceptibility to malignancy
A complication of sickle cell disease is an increased formation of galstones. Why does this occur?
Sickle cell crisis accompanied by the intravascular destruction of red blood cells (hemolysis) experienced by patients with sickle cell disease
This occurs because the conjugation of bilirubin cannot keep up with the high amount of unconjugated bilirubin that is incoming into the liver, thus unconjugated bilirubin is secreted into the bile. Unconjugated bilirubin is not water soluble so it tends to create/form gallstones.
During iron deficiency, the cells are smaller and paler than normal. Why?
The lack of iron results in decreased heme synthesis, which in turn affects globin synthesis. Maturing red cells following their normal developmental program divide until their hemoglobin has reached the appropriate concentration. Iron (and hemoglobin)-deficient developing red blood cells continue dividing past their normal stopping point, resulting in small (microcytic) red cells. The cells are also pale—because of the lack of hemoglobin—compared with normal cells (thus, a pale, microcytic anemia results).
Deficiencies of folate or vitamin B12 can cause ________1_________ _______________, in which the cells are larger than normal. How does this occur?
Folate and B12 are required for_______ ______________ .
1. megaloblastic anemia
2. DNA synthesis
When these vitamins are deficient, DNA replication and nuclear division do not keep pace with the maturation of the cytoplasm. Consequently, the nucleus is extruded before the requisite number of cell divisions has taken place, and the cell volume is greater than it should be, and fewer blood cells are produced.
Another common hemoglobin variant (to S hemoglobin), hemoglobin C (HbC), results from a ______________ replacement in the same position as the HbS mutation.
Hemoglobin C has two effects: ____________________
1. It promotes water loss from the cell by activating the K+ transporter by an unknown mechanism, resulting in a higher than normal concentration of hemoglobin within the cell.
2. The amino acid replacement also substantially lowers the hemoglobin solubility in the homozygote, resulting in a tendency of the mutant hemoglobin to precipitate within the red cell, although, unlike sickle cells, the cell does not become deformed.
Homozygotes for the HbC mutation have a ____________ ____________ __________. Heterozygous individuals are ____________ ____________
1. mild hemolytic anemia
2. clinically unaffected.
The difference in amino acid composition between the beta-chains of HbA and the gamma-chains of fetal hemoglobin (HbF) results in structural changes that cause HbF to have a lower affinity for ___________________________ than adult hemoglobin (HbA) and thus a greater affinity for oxygen. Therefore, the oxygen released from the mother's hemoglobin (HbA) is readily bound by HbF in the fetus. Thus, the transfer of oxygen from the mother to the fetus is facilitated by the structural difference between the hemoglobin molecule of the mother and that of the fetus.
Patients with hemoglobinopathies such as beta-thalassemia or sickle cell anemia frequently have less severe illnesses if their levels of _______ are elevated.
Individuals who express HbF past birth have hereditary persistence of fetal hemoglobin (HPFH).
Globin gene clusters and expression during development.
Megaloblast (embryonic RBCs) production in:
Yolk sac = first 2 weeks after fertilization
Shifts to Liver and Spleen = after 6 weeks
Bone marrow begins production of RBCs = last few weeks before birth
Only bone marrow = 8-10 weeks after birth
The globin gene clusters with the alpha-genes on chromosome ____1____ and the beta-genes on chromosome ___2____.
What is the compensatory mechanism to allow adequate oxygen delivery to the tissues at high altitudes, where oxygen concentrations are low?
An increase in 2,3-bisphosphoglycerate synthesis by the red cell
Lead poisoning leads to an anemia attributable to a deficiency in what?
Heme group (its formation is inhibited)
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