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What is Anemia? Anemia is a decrease in the Anemia is a decrease in the number of red blood cells number of red blood cells (RBC) as measured (RBC) as measured 1. per cu mm on a slide or 1. per cu mm on a slide or 2. by volume of packed RBC 2. by volume of packed RBC per 100 ml of blood. This is per 100 ml of blood. This is clinically obtained by doing clinically obtained by doing a hematocrit (HCT) a hematocrit (HCT)
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Page 1: Anemia

What is Anemia? Anemia is a decrease in the number of red Anemia is a decrease in the number of red

blood cells (RBC) as measured blood cells (RBC) as measured 1. per cu mm on a slide or 1. per cu mm on a slide or 2. by volume of packed RBC per 100 ml 2. by volume of packed RBC per 100 ml

of blood. This is clinically obtained by of blood. This is clinically obtained by doing a hematocrit (HCT)doing a hematocrit (HCT)

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There are several causes of anemia 1. RBC Loss without RBC destruction1. RBC Loss without RBC destruction 2. Deficient RBC production 2. Deficient RBC production 3. Increased RBC destruction over 3. Increased RBC destruction over

productionproduction

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RBC loss without RBC Destruction

Hemorrhage Hemorrhage Due to traumaDue to traumaDue to disorders: e.g.cancer, ulcers, Due to disorders: e.g.cancer, ulcers,

tuberculosis, diverticular disease, and tuberculosis, diverticular disease, and irritable bowel syndrome (including irritable bowel syndrome (including ulcerative colitis and Crohn’s disease) ulcerative colitis and Crohn’s disease)

Menstrual flowMenstrual flow Gynecological disorders (e.g. endometriosis, Gynecological disorders (e.g. endometriosis,

fibroids) fibroids) Pregnancy, especially at gestationPregnancy, especially at gestation Parasitism Parasitism

HookwormsHookworms

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Deficient RBC Production NeoplasiaNeoplasia

LeukemiaLeukemia Metastasis to bone marrowMetastasis to bone marrow Osteogenic sarcomaOsteogenic sarcoma

MyelofibrosisMyelofibrosis Pernicious anemiaPernicious anemia Iron Deficiency anemiaIron Deficiency anemia Aplastic anemia Aplastic anemia

Chloramphenicol administrationChloramphenicol administration Renal disease (lack of erythropoietin production)Renal disease (lack of erythropoietin production)

Increased RBC destruction over erythropoiesisIncreased RBC destruction over erythropoiesis

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Increased RBC Destruction over Production (Hemolytic Anemias)

Intrinsic AbnormalitiesIntrinsic Abnormalities ThalassemiaThalassemia G6PDG6PD Sickle Cell AnemiaSickle Cell Anemia Hereditary SpherocytosisHereditary Spherocytosis

Extrinsic AbnormalitiesExtrinsic Abnormalities InfectionsInfections

• Malaria (Malaria (PlasmodiummPlasmodiumm species) species)• MycoplasmaMycoplasma

Disseminated Intravascular CoagulationDisseminated Intravascular Coagulation Lead poisoning Lead poisoning

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Symtomatology.

Symptoms develop in proportion to the Symptoms develop in proportion to the degree of anemia.degree of anemia.

Increasing fatigability, headache, Increasing fatigability, headache, tachycardia, exertional dyspnea, ankle tachycardia, exertional dyspnea, ankle edema, and pallor.edema, and pallor.

Pica eating is a striking feature of anemia.Pica eating is a striking feature of anemia. Pagophagia, Amylophagia, and Geophagia.Pagophagia, Amylophagia, and Geophagia.

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Symtomatology…

Abnormalities in epithelial tissue including Abnormalities in epithelial tissue including sore or atrophic tongue, sore mouth, angular sore or atrophic tongue, sore mouth, angular stomatitis, thinning or Spooning of nails stomatitis, thinning or Spooning of nails (Koilonychia) and dysphagia may occur.(Koilonychia) and dysphagia may occur.

Plummer-vinson syndrome (Sideropenic Plummer-vinson syndrome (Sideropenic dysphagia) is characterized by the feeling of dysphagia) is characterized by the feeling of food sticking in the throat.food sticking in the throat.

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Symptomatology…

Menstrual abnormalities are common- Menstrual abnormalities are common- Menorrhagia, irregularity of flow, or even Menorrhagia, irregularity of flow, or even amenorrhea.amenorrhea.

When present, menorrhagia may aggravate When present, menorrhagia may aggravate the iron deficiency.the iron deficiency.

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Symptomatology…

In the fully developed state, the clinical picture is In the fully developed state, the clinical picture is striking:striking:

A tired listless appearance, pallor, inelastic &often A tired listless appearance, pallor, inelastic &often dry and wrinkled skin, dry & often scanty hair, dry and wrinkled skin, dry & often scanty hair, pearly white sclera, and pale conjunctiva are pearly white sclera, and pale conjunctiva are found.found.

Papillary atrophy of tongue, slight cardiac Papillary atrophy of tongue, slight cardiac enlargement and functional systolic murmur.enlargement and functional systolic murmur.

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Diagnosis.

The fall in blood Hemoglobin level is of a The fall in blood Hemoglobin level is of a greater magnitude than the hematocrit.greater magnitude than the hematocrit.

Peripheral blood smear shows anisocytosis Peripheral blood smear shows anisocytosis and poikilocytosis.and poikilocytosis.

Mean copuscular volume and mean Mean copuscular volume and mean corpuscular Hemoglobin is reduced.corpuscular Hemoglobin is reduced.

Serum Iron is bellow 30/Mcrogram /dl.Serum Iron is bellow 30/Mcrogram /dl.

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Diagnosis…

Total Iron binding capacity is increased. Total Iron binding capacity is increased. (600 micrograms/dl.)(600 micrograms/dl.)

Prussian blue staining of bone marrow Prussian blue staining of bone marrow shows absence of hemosiderin.shows absence of hemosiderin.

A significant reticulocytosis occurring after A significant reticulocytosis occurring after commencement of iron administration commencement of iron administration indicates a response.indicates a response.

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In therapeutic trial period of 3-4 weeks , In therapeutic trial period of 3-4 weeks , hemoglobin should increase on an average hemoglobin should increase on an average of 0.2gram/100 ml.of 0.2gram/100 ml.

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Selected Pharmacology of Anemias – RBC Loss Therapy: Packed RBC cells – never whole Therapy: Packed RBC cells – never whole

bloodblood Why? Why? Ans: whole blood contains too much Ans: whole blood contains too much

potassium from dead cells which lyse. potassium from dead cells which lyse. Cardiac arrhythmias ensue.Cardiac arrhythmias ensue.

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Selected Pharmacology of Anemias – Deficient RBC Production

Neoplasia: covered by another lecturerNeoplasia: covered by another lecturer Myelofibrosis: Remove spleen; transfusion when Myelofibrosis: Remove spleen; transfusion when

necessary with packed cells.necessary with packed cells. Pernicious anemia: B12 injectionsPernicious anemia: B12 injections Microcytic (iron deficiency) anemia: iron: only ferrous Microcytic (iron deficiency) anemia: iron: only ferrous

iron (iron (sulfatesulfate, fumarate, gluconate). Ferric iron is not , fumarate, gluconate). Ferric iron is not absorbed – liquid Geritol won’t do. absorbed – liquid Geritol won’t do.

Aplastic anemia: stop medication; may have to do bone Aplastic anemia: stop medication; may have to do bone marrow transplantmarrow transplant

Renal disease: Correct if possible, otherwise renal Renal disease: Correct if possible, otherwise renal transplanttransplant

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Normal, RBC's. Normal, RBC's. They have a They have a zone of central zone of central pallor about 1/3 pallor about 1/3 the size of the the size of the RBC.). A few RBC.). A few small fuzzy blue small fuzzy blue platelets are platelets are seen. In the seen. In the center of the center of the field are a band field are a band neutrophil on the neutrophil on the left and a left and a segmented segmented neutrophil on the neutrophil on the right.right.

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The RBC's here are smaller than normal and have an increased zone of central pallor. This is indicative of a hypochromic (less hemoglobin in each RBC) microcytic (smaller size of each RBC) anemia. There is also increased anisocytosis (variation in size) and poikilocytosis (variation in shape).

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The most common cause for a hypochromic The most common cause for a hypochromic microcytic anemia is iron deficiency. The most microcytic anemia is iron deficiency. The most common nutritional deficiency is lack of dietary common nutritional deficiency is lack of dietary iron. Thus, iron deficiency anemia is common. iron. Thus, iron deficiency anemia is common. Persons most at risk are children and women in Persons most at risk are children and women in reproductive years (from menstrual blood loss reproductive years (from menstrual blood loss and from pregnancy).and from pregnancy).

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This peripheral blood smear comes from a This peripheral blood smear comes from a patient with malaria caused by patient with malaria caused by Plasmodium Plasmodium vivaxvivax. At the arrow on the right is a RBC with a . At the arrow on the right is a RBC with a malarial parasite in the shape of a ring. Three malarial parasite in the shape of a ring. Three other RBC's in this smear are also infected with a other RBC's in this smear are also infected with a ring trophozoite. Arrow at left is a gametocyte of ring trophozoite. Arrow at left is a gametocyte of this species.this species.

Mal

aria

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Erythropoiesis (Formation of RBCs)

Erythropoiesis begins with a pluripotent Erythropoiesis begins with a pluripotent stem cell whose progeny are influenced by stem cell whose progeny are influenced by hormones to develop into several cell lines.hormones to develop into several cell lines.

One of these cells lines becomes committed One of these cells lines becomes committed to the erythroid line of development.to the erythroid line of development.

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Erythropoiesis (Formation of RBCs)

1. The initial cell is a BFU-E (burst forming 1. The initial cell is a BFU-E (burst forming unit – erythroid)unit – erythroid)

2. BFU-E in the presence of interleukin-3 2. BFU-E in the presence of interleukin-3 and erythropoietin forms CFU-E (colony and erythropoietin forms CFU-E (colony forming units – erythroid).forming units – erythroid).

3. CFU-E in the presence of a high 3. CFU-E in the presence of a high concentration of erythropoietin forms a concentration of erythropoietin forms a pronormoblast.pronormoblast.

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Erythropoiesis (Formation of RBCs)

4. The pronormoblast – large nucleated cell 4. The pronormoblast – large nucleated cell but NO hemoglobinbut NO hemoglobin

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Erythropoiesis (Formation of RBCs) 5. Normoblast – 5. Normoblast –

characterized by characterized by increased hemoglobin increased hemoglobin synthesis.synthesis. During this stage, During this stage,

cytoplasmic cytoplasmic organelles are lost.organelles are lost.

During the late normoblast During the late normoblast stage, the nucleus is ejected. stage, the nucleus is ejected. Once ejected, the cell is called a Once ejected, the cell is called a reticulocyte.reticulocyte.

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Erythropoiesis (Formation of RBCs)

6. The reticulocyte (arrow)6. The reticulocyte (arrow) Has no nucleusHas no nucleus Has no organellesHas no organelles Is larger than the mature RBCIs larger than the mature RBC Is not concaveIs not concave Has many polyribosomesHas many polyribosomes In severe anemia, many of these are In severe anemia, many of these are

released into the blood prematurely.released into the blood prematurely. Normally, 25 billion cells, which is Normally, 25 billion cells, which is

1% of circulating blood, are 1% of circulating blood, are reticulocytesreticulocytes

Ribosomal RNA stained with methylene blue

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Notes on Terminology Pronormoblast and normoblast are terms Pronormoblast and normoblast are terms

that relate to the normal development of the that relate to the normal development of the erythrocyte in contrast to the megaloblastic erythrocyte in contrast to the megaloblastic formation seen in megaloblastic anemia.formation seen in megaloblastic anemia.

The erythroid stages are depicted as The erythroid stages are depicted as Proerythroblast = pronormoblastProerythroblast = pronormoblast

Basophilic erythroblastBasophilic erythroblastPolychromatic erythroblastPolychromatic erythroblastOrthochromatic erythroblastOrthochromatic erythroblast

Reticulocyte (polychromatic erythrocyte)Reticulocyte (polychromatic erythrocyte)

nor

mob

last

s

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Normoblasts

Pronormoblast

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Factors necessary for erythropoiesis 1. Erythropoietin1. Erythropoietin 2. Iron2. Iron 3. Vitamin B3. Vitamin B1212 (cyanocobalamin) (cyanocobalamin)

4. Folic Acid (folate)4. Folic Acid (folate) 5. Ascorbic acid (Vitamin C)5. Ascorbic acid (Vitamin C) 6. Pyridoxine (Vitamin B6. Pyridoxine (Vitamin B66))

7. Amino acids7. Amino acids

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Regulation of Erythropoiesis

Normal body requirements for oxygen is Normal body requirements for oxygen is 250 ml/min250 ml/min

Almost all of that is for use in oxidative Almost all of that is for use in oxidative phosphorylation by the mitochondria.phosphorylation by the mitochondria.

The heart normally pumps out 1,000 ml The heart normally pumps out 1,000 ml oxygen per minute. oxygen per minute.

Less than 250 ml/min causes tissue hypoxiaLess than 250 ml/min causes tissue hypoxia

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Regulation of Erythropoiesis

Kidneys receive 25% of cardiac output – Kidneys receive 25% of cardiac output – approximately 1,250 ml of blood/min – yet approximately 1,250 ml of blood/min – yet it is only 0.5% of body weight. it is only 0.5% of body weight.

The 1,250 ml/min contains 250 ml/min of The 1,250 ml/min contains 250 ml/min of oxygenoxygen

The amount of oxygen/min received by the The amount of oxygen/min received by the kidneys is the same as that required by body kidneys is the same as that required by body tissues/min. tissues/min.

Therefore, renal monitoring of oxygen is Therefore, renal monitoring of oxygen is logical choice.logical choice.

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Regulation of Erythropoiesis

If renal tissue is hypoxic, erythropoietin is If renal tissue is hypoxic, erythropoietin is produced by renal peritubular interstitial produced by renal peritubular interstitial cells.cells.

The gene for erythropoietin is located on The gene for erythropoietin is located on chromosome 7.chromosome 7.

Erythropoietin is not the only factor Erythropoietin is not the only factor required for red cell development. We will required for red cell development. We will cover some of these later.cover some of these later.

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Regulation of Erythropoiesis

While the kidney produces most of the While the kidney produces most of the erythropoietin, the liver and other tissues erythropoietin, the liver and other tissues also produce some.also produce some.

In fetal life, the liver produced all of the In fetal life, the liver produced all of the

erythropoietin – as the final kidney – the erythropoietin – as the final kidney – the metanephros - had not yet completed metanephros - had not yet completed development.development.

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Regulation of Erythropoiesis

Erythropoietin increases RBC production in Erythropoietin increases RBC production in 3 ways:3 ways: Promotes pronormoblast productionPromotes pronormoblast production Shortens the transition time through the Shortens the transition time through the

normoblast stagenormoblast stage Promotes the early release of Promotes the early release of

reticulocytes.reticulocytes.

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Regulation of Erythropoiesis

How many are produced:How many are produced: 25 billion /24 hours. 25 billion /24 hours. The entering cells are reticulocytes which The entering cells are reticulocytes which

should be 1% of the total population of should be 1% of the total population of circulating erythrocytes.circulating erythrocytes.

Erythrocytes last 120 days and are Erythrocytes last 120 days and are destroyed by the spleen.destroyed by the spleen.

Red cell production should equal red cell Red cell production should equal red cell destruction.destruction.

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Determination of RBC size

MCV = mean corpuscular volume in MCV = mean corpuscular volume in femtoliters (10femtoliters (10-15-15 liters) abbreviated fl. liters) abbreviated fl.

This is the most accurate method of measuring This is the most accurate method of measuring red blood cells and is the one done by red blood cells and is the one done by automated Coulter counters.automated Coulter counters.

MCH = mean corpuscular hemoglobin does not MCH = mean corpuscular hemoglobin does not add anything to the diagnosis except additional add anything to the diagnosis except additional expense. It will not be considered further.expense. It will not be considered further.

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Differential Diagnosis using MCV Macrocytic anemias (MCV = 150 fl) – Macrocytic anemias (MCV = 150 fl) –

larger than normal cellslarger than normal cells

Normocytic (MCV = 80-96 fl) – cells are Normocytic (MCV = 80-96 fl) – cells are normal in volume.normal in volume.

Microcytic anemias (MCV = 50 fl) – cells Microcytic anemias (MCV = 50 fl) – cells are smaller than normal.are smaller than normal.

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Our discussion of anemia is limited to:

We will only discuss those anemias that are due to We will only discuss those anemias that are due to a deficiency of:a deficiency of: Iron Iron Folic acid Folic acid Vitamin B12 Vitamin B12 VitaminVitamin

Or those anemias that will be benefitted by the Or those anemias that will be benefitted by the administration of erythropoietin.administration of erythropoietin.. .

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Erythropoietin Recombinant human erythropoietin is Recombinant human erythropoietin is

produced using Chinese hamster ovarian produced using Chinese hamster ovarian cell line.cell line.

There are differences in the carbohydrate There are differences in the carbohydrate portion of the molecule but it neither portion of the molecule but it neither stimulates the immune system nor affects stimulates the immune system nor affects potency or efficacy. potency or efficacy.

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Erythropoietin Epoetin alpha (Eprex) is available in Epoetin alpha (Eprex) is available in

Saskatchewan in prefilled syringes and Saskatchewan in prefilled syringes and sterile solution for injection. sterile solution for injection.

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Erythropoietin is used to treat:

1. Anemia in chronic renal disease prior to 1. Anemia in chronic renal disease prior to dialysis (there is always destruction of RBC dialysis (there is always destruction of RBC in dialysis as the blood goes through the in dialysis as the blood goes through the dialysis pump)dialysis pump)

2. Anemia in AIDS patients2. Anemia in AIDS patients 3. Anemia in transplant patients3. Anemia in transplant patients

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Erythropoietin is used to treat: 4. Anemia in cancer patients who have undergone 4. Anemia in cancer patients who have undergone

chemotherapy that destroyed some of the bone chemotherapy that destroyed some of the bone marrow.marrow.

5. Anemia in surgical or extracorporeal procedures 5. Anemia in surgical or extracorporeal procedures (e.g.: CABG and AVM) because the pumps may (e.g.: CABG and AVM) because the pumps may have destroyed many red blood cells.have destroyed many red blood cells.

6. Anemia in premature children.6. Anemia in premature children.

7. Chronic inflammatory illnesses (e.g. systemic 7. Chronic inflammatory illnesses (e.g. systemic lupus erythematosus) in which RBCs are lupus erythematosus) in which RBCs are destroyed.destroyed.

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Erythropoietin is abused:

Athletes use erythropoietin to enhance their Athletes use erythropoietin to enhance their athletic prowess.athletic prowess.

Using erythropoietin in this way is called Using erythropoietin in this way is called blood doping.blood doping.

Blood doping increases the concentration of Blood doping increases the concentration of RBCs and with it an increased chance for RBCs and with it an increased chance for spontaneous coagulation.spontaneous coagulation.

Several athletes have died as a result.Several athletes have died as a result. It is not allowed by international sports It is not allowed by international sports

associations, such as the International associations, such as the International Olympic Committee.Olympic Committee.

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Iron Iron deficiency is the most common cause Iron deficiency is the most common cause

of anemia.of anemia. Results in microcytic hypochromic anemia.Results in microcytic hypochromic anemia.

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Iron is used in: Hemoglobin.Hemoglobin. Heme enzymes, e.g., cytochromes, catalase,Heme enzymes, e.g., cytochromes, catalase,

peroxidaseperoxidase MyoglobinMyoglobin Metalloflavoprotein enzymes such as xanthine Metalloflavoprotein enzymes such as xanthine

oxidaseoxidase The mitochondrial enzyme alpha-glycerophosphate The mitochondrial enzyme alpha-glycerophosphate

oxidase and other mitochondrial enzymes.oxidase and other mitochondrial enzymes. Other enzymes and processes Other enzymes and processes

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Iron in hemoglobin

Page 44: Anemia

Iron in hemoglobin

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Iron Deficiency – Common Causes Inadequate dietary intake of iron especially Inadequate dietary intake of iron especially

in:in: Infants in the postnatal periodInfants in the postnatal period Young females after menarcheYoung females after menarche Adolescents of both sexesAdolescents of both sexes During pregnancyDuring pregnancy

Page 46: Anemia

Iron Deficiency – Common Causes (cont) Partial gastrectomy due to ulcersPartial gastrectomy due to ulcers Blood loss due to:Blood loss due to:

Bleeding peptic ulcersBleeding peptic ulcers MalignancyMalignancy Trauma in which there is excessive bleeding Trauma in which there is excessive bleeding

(includes blood loss through extensive (includes blood loss through extensive bruising)bruising)

Malabsorption syndromesMalabsorption syndromes Cystic fibrosisCystic fibrosis Celiac Disease (nontropical sprue)Celiac Disease (nontropical sprue)

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Iron Deficiency – lead toxicity

Can lead to lead toxicity from picaCan lead to lead toxicity from pica Iron deficiency enhances uptake of heavy Iron deficiency enhances uptake of heavy

metals, including lead.metals, including lead. Lead is still used in all outside house Lead is still used in all outside house

paint.paint. Lead is highly concentrated in the first Lead is highly concentrated in the first

few inches of soil in cities – from car few inches of soil in cities – from car exhaust of 20 years or more ago.exhaust of 20 years or more ago.Infants love to each pica – their taste of Infants love to each pica – their taste of

the world.the world.

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Heme iron and nonheme iron

Heme iron very well absorbed. Present in Heme iron very well absorbed. Present in muscle as part of myoglobin.muscle as part of myoglobin.

But: Do not eat meat that is bloody. But: Do not eat meat that is bloody. Bacteria love blood and it can be the source Bacteria love blood and it can be the source of severe food poisoning.of severe food poisoning.

Nonheme iron not absorbed well but forms Nonheme iron not absorbed well but forms the bulk of dietary iron.the bulk of dietary iron.

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Iron – Absorption

Absorbed from the duodenum (where most Absorbed from the duodenum (where most drugs are absorbed) and upper jejunum.drugs are absorbed) and upper jejunum.

Vitamin C taken with the iron increases Vitamin C taken with the iron increases absorption by reducing dietary ferric to absorption by reducing dietary ferric to ferrous iron. ferrous iron.

Caffeine and other xanthines decrease Caffeine and other xanthines decrease absorption. absorption.

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Iron – Preparations available

Only absorbed well in the ferroOnly absorbed well in the ferrousus (“us” is (“us” is for us) form. Ferrous sulphate, ferrous for us) form. Ferrous sulphate, ferrous gluconate and ferrous fumarate are three gluconate and ferrous fumarate are three that are available.that are available.

FerrFerricic form only 10% absorbed – ick! Ferric form only 10% absorbed – ick! Ferric ammonium citrate is in Geritol Tonic. ammonium citrate is in Geritol Tonic.

However, patients feel good – could it be However, patients feel good – could it be because of the 12% alcohol content?because of the 12% alcohol content?

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Iron – Not from Geritol Tonic

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Iron Therapy – Side effects of oral preparations Nausea Nausea Gastric discomfortGastric discomfort ConstipationConstipation DiarrheaDiarrhea

Good idea to start patients on small doses and Good idea to start patients on small doses and increase gradually. Less side effects that increase gradually. Less side effects that way.way.

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Iron – Parenteral solution Should be used cautiously because 0.2% to Should be used cautiously because 0.2% to

3% of patients develop hypersensitivity 3% of patients develop hypersensitivity including anaphylactic shock to parenteral including anaphylactic shock to parenteral iron.iron.

Parenteral iron does not appear to provide a Parenteral iron does not appear to provide a faster response than oral preparations.faster response than oral preparations.

Only one in Saskatchewan: iron dextranOnly one in Saskatchewan: iron dextran Reasons for use:Reasons for use:

Renal failureRenal failureShort bowelShort bowelCeliac disease (sprue)Celiac disease (sprue)

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Megaloblastic (macrocytic) anemia Due to lack of folic acid or vitamin B12Due to lack of folic acid or vitamin B12 Folate (folic acid) interacts with vitamin Folate (folic acid) interacts with vitamin

B12.B12. Essential for normal blood and nerve Essential for normal blood and nerve

function.function. CanCan

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Vitamin B12

Also called the extrinsic factorAlso called the extrinsic factor Must combine with intrinsic factor Must combine with intrinsic factor

produced by the parietal glands of the produced by the parietal glands of the stomach.stomach.

The combination enables binding to The combination enables binding to receptor and phagocytosis of the complex receptor and phagocytosis of the complex by the distal ileum cells. by the distal ileum cells.

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Vitamin B12

Lack of vitamin B12 is called pernicious Lack of vitamin B12 is called pernicious anemia.anemia.

It is usually a result of an autoimmune It is usually a result of an autoimmune disease that destroys the parietal cells of the disease that destroys the parietal cells of the stomach.stomach.

The patients also have achlorohydria which The patients also have achlorohydria which also results in halitosis. also results in halitosis.

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Vitamin B12

Vitamin B12Vitamin B12 Must be ingested – is not synthesized in Must be ingested – is not synthesized in

bodybody Sources:Sources:

MeatMeatEggsEggsDairy productsDairy products

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Vitamin B12

Is also present in multivitamin preparationsIs also present in multivitamin preparations Can also be administered by injection in Can also be administered by injection in

pernicious anemia as cyanocobalamin.pernicious anemia as cyanocobalamin.

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Vitamin B12 or Folic Acid

Lack of either prevents formation of DNA so RBC Lack of either prevents formation of DNA so RBC production does not occur or occurs abnormally.production does not occur or occurs abnormally. Macrocytic cells (large cells) which may have Macrocytic cells (large cells) which may have

enough Hb, but are not concave and are fewer enough Hb, but are not concave and are fewer in number.in number.

Therefore, cannot take up or transport oxygen Therefore, cannot take up or transport oxygen normally.normally.

The cells are more easily damaged – also The cells are more easily damaged – also contributing to the anemia contributing to the anemia

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Macrocytic anemia

Note the hypersegmented neurotrophil and also that the RBC are almost as large as the lymphocyte. Finally, note that there are fewer RBCs.

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Macrocytic anemia - causes

Inadequate folate intakeInadequate folate intake AlcoholicsAlcoholics TeenagersTeenagers Some infantsSome infants

Malabsorption – may be due to barbiturates, Malabsorption – may be due to barbiturates, phenytoin, and oral contraceptives.phenytoin, and oral contraceptives.

Impaired metabolism – may be due to Impaired metabolism – may be due to methotrexate or rare enzyme deficiencies.methotrexate or rare enzyme deficiencies.

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Folic acid therapy

Recommended natural folate sources:Recommended natural folate sources: Green vegebablesGreen vegebables NutsNuts CerealCereal FruitFruit YeastYeast Liver – but only from certain farm sourcesLiver – but only from certain farm sources

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Folic acid therapy

Folate therapeutics:Folate therapeutics: Usually in multivitamin preparationsUsually in multivitamin preparations Also, as folic acid, 5mg tablets.Also, as folic acid, 5mg tablets.