Red Blood Cell Disorders

What are lead denatured enzymes?

1. Ferrochelatase is denatured (hemesynthase) a. Iron cannot bind with protoporphyrin to form heme b. FEP, which is proximal to the enzyme block, is increased 2. Aminoevulinic acid (ALA) dehydrase is denatured, causes an increase in ∫-ALA, which is proximal to the enzyme block 3. RIbonuclease is denatured a. ribsomes cannot bedegreaded and therefore persis in the RBC b. Results of denaturatin is course basophillic stiplling c. Lead interferes wtih iron absorotption anditilization in heme pathways, some authros state that the microcytosis in lead poisoning is due to iron deficiency

What is the hemoglobin electrophoresis?

1. Hb electrophoresis is used to detect hemoglobinopathies , which include:o a. Abnormalities in globin chain structure (sickle cell disease) b. Abnormalilites in globin chain synthesis (thalassemia) 2. types of normal Hb detected a. HbA has 2∂/2ß globin chains (97%) b HbA2 has 2∂/2theta globin chains (2% in adults) c. HbF has 2∂/2y globin chains (1% in adults) 3. Examples of abnormal Hb detectred include: Sickle Hb, HbH, and Hb Bart

What are the components of the complete blood cell count?

1. Hemoglobin (Hb), Hct, RBC count 2. RBC indices, RBC distribution width (RDW) 3. WBC count with a differential count and platelet count 4. Evaluation of the peripheral blood morphoology

What is ß-thal major?

Cooleys anemia 1) Severe hemolytic anemia a. RBC with ∂ chain inclusions are removed by splenic macrophages. Marked increase in unconjugated bilirubin (UCB:jaundice) b. RBCs with ∂-chain inclusions undergo apoptosis in the bone marrow(ineffective erythropoiesis) 2. EMH and accelerated erythropoiesis a. Hepatosplenmegaly from excessive hematopoiesis b. Radiographs of the skill show a hair on end appearance 3.Increased RDW due to increae size variation 4. Increase in reticulocytes, teardrop cells, howell jolly bodies (nuclear remants) and nucleated RBCs 5)Hb electrophoresis a) Nosynthesis of HbA b> corresponding increase in HbA2 and Hbf 6. Treatment is a) blood tranfusion with the danger of iron overload called (hemosiderosis). requires chelatin therpapy with desferrioxamine. b)bone marrow transplantation(only curative approach.

What is the serum total iron binding capacity (TIBC)?

Correlates with the concentration of transferrin b. relationship of transferrin synthesis with ferritin stores in macrophages 1)Decreased ferritin stores leads to increased liver synthesis of trnaferrin. 2) increased ferritin stores leads to decreased liver synthesis of tranferrin. Decrease in transferrin and TIBC occurs in ACD and iron overload disease c. Primary function of transferrin is to deliver ferric iron (Fe3+) to erythroid precursors in the bone marrow. Iron on transferrin comes from bone marrow macrophages and from the duodenum the primary site for iron reabsorption.

How do the cells function while passing through circulation? What kind of hemolysis occurs? What about hematopoiesis?

E Cells continously sickle and de-sicckle while passing through the microcirculation resulting in complications related to RBC membrane damage. 1. Extravascular hemolysis- Reticuloendothelial system removes RBCs with damage membranes and become less flexible, leading to anemia, juandice with unconjugated hyperbilirubinemia, and increased risk for bilirubnin gallstones. 2. Intravascular hemolysis-RBCs with damaged membranes dehydrate, leading to hemolysis with decreased haptoglobin and target cells on blood smear. 3.Massive erythroid hyperplasia ensues resulting in i. Expansion of heamtopoiesis into the skull (crewcut appearance on xrays) and facial bones (chipmunk facies). ii. Extraamedullary hematopoiesis with hepatomegaly iii. Risk of aplastic crisis with parvovirus B19 infection of erythroid precursors.

What is the iron absorption and regulation?

2. Iron absorption and regulation a. Gastric acid frees elemental iron from heme and nonheme products. Underscores why achlorhydria (absent stomach acid) decreases the availability of iron for absorption. b. Iron from plants is in a nonheme or oxidized from (ferric Fe3+) 1) cannot be acbsorbed in the duodenum 2. converted by cytochrome B in the duodenal mucosa into reduced iron (Fe2) 3) reduced iron absorbed by divalen metal transporter 1 (DMT1) into the mucosal cell. C. Iron from meat is in ta heme or reduced form (ferrous Fe2+) Ferrous form of iron is directly absorbed in the duodenum by heme carrier protein 1. d. Absorbed iron is stored as mucosal ferritin or it enters the ferroportin 1 port and is immediately converted by hephaestin or ceruloplasmin to ferric iron (Fe3+) so that it can bind to transferrin in the blood . Transferrin bring iron to devevloping erythroid precursors in the marrow.

What is microangiopathic hemolytic anemia?

A. Intravascular hemolysis that results from vasular pathology; due to some thrombus that partially blocks a blood vessel and shears the RBS forming schistocytes and these cells are the hallmark of MHA. RBCs are destroyed as they pass through the circulation. 1. Iron deficiency anemia occurs with chronic hemolysis B. Occurs with microthrombi (TTP (platelet thrombi due to lack of ADAMSTS13)-HUS (platelet microthrombi but due to a toxin creasted by E coli OH157), DIC (paltelet pus fibrin enzyme), HELLP (pregnant women can develop MHA within liver due to the production of these thrombi ), Occurs with prosthertic heart valves becuase the valves crush RBC and destroy them, and aortic stenosis and also the calcified degenerative valve will crush the RBCs and destroy them , when present, microthrombi produce schistocytes on blood smear.

what is the Anemia of chronic disease (ACD)?

A. Most common anemia in hospitalized patients. b. Common cuases 1. Chronic inflammation. Rheumatoid arthritis, tuberculosis(TB), and Crohn disease 2) alcoholism, ACD is the most common anemia in alcoholism 3. Malignancy, ACD is the most common anemia in malignancy

What is myelophthisic process?

A. Pathologic process (meastatic cancer) that replaces bone marrrow; hematopoiesis is imparied, resulting in pancytopenia.

What preparation allows the dto see the Heinz bodeis

E. Heinz preparation is used to screen for disease (precipitated hemoglobin can only be seen with a special Heinz stain) enzyme studies confirm deficiency (performed weeks after hemolytic episode resolves because if you test at the time of hemolysis then all of the cells lacking the enzyme would be dead and when you test the remaining red cells tho.)ve the enzyme

What are the clinical features of iron defeciency?

Anemia Koilonychia, spoon shaped finger nails pica, chew on abnormal things seeking iron

WHat can caue iron deficiency?

E. Iron deficiency is usually caused by dietary lack or blood loss. 1. Infants- breast feeding (human milk is low in iron) 2. Children-Poor diet 3. Adults (20-50years)- peptic ulcer disease in males and menorrhagia or pregnancy in females due to a large amount of iron to grow the fetus 4Elderyly- colon polyps/carcinoma in the western world; hookworm (ancylostoma duodenale and necator americanus) in the developing world 5. Other causes include malnutrition, malabsorption that can destroy the duodenum like the villi being destroyed in celiac disease, and gastrectomy due to a portion of the stomach being removed causing a decrease in acid production (acid aids iron absorption by maintaining the Fe2+ state (Fe2 goes in2 the body), which is more readily absorbed than Fe3+)

What cell in the bone marrow forms the RBC

Erythroblast is the cell that forms the RBC and it is a large cell thawt continoulsy divide to form the RBC

What is the serum iron?

Iron that is bount to transferrin. Transferrin is the binding protein of iron and is synthesized in the liver b. Serum iron is the shaded area of the column. Note that the normal serum iron level is100 microgram per decaliter. c. Iron shown coming into the macrophages is coming from the degradation of senescent macrophages, not from transferrin. Amount of iron coming into the macrophage is equal to the amount of iron leaving the macrophage to bind with transferrin d. Decreased serum iron occurs in iron deficiency. e. Increased serum iron occurs in iron overload diseases .Example of iron overleoad diseases include the sideroblastic anemias and hemochromatosis.

Wha

Normal ß chain syntheisis is designatedß, some ß-globin chain synthesis is designated ß+ absence of ß globin chain syntehsis is designateds ßo

What is the red blood cell distribution width(RDW)?

Reflects any significant variation in size of the peripheral blood RBCs 1) Size variation is called anisocytosis 1)value is only significant if it is increased b Increased if RBCs are not uniformly the same size. ex is the mixture of microcytic and normocytic cells c. Useful in distinguishing iron deficiency from other causes of micro cytic anemia 1) Iron deficiency is the most common microcytic anemia with an increased RDW. Due to a mixture of normocytic and microcytic RBCs in the peripheral blood in iron deficiency. 2) with other microcytic anemias, particularly anemia of chronic disease (ACD) and thalassemia, RBCs appear more uniform.

What are the stages of iron deficiency?

Say the patient has a hookworm and its using up the iron. so ...the first .place that iron will be retrieve and released is the1. Storage iron is depleted-decreased ferritin; increase TIBC 2. Serum iron is depleted-decrease serum iron; decrease % saturation (normal is 33%) 3. Normocytic anemia- as iron is being edepleted form the storage sights and being depleted from the serum but since it cannot produce heme due to the lack of heme the bone marrow prefers to make pretty RBC so instead the Bone marrow makes fewer, but normal seized, RBCs. ( which ia avery early stage of niron deficiency anemia is normocytic b ut hen the iron deficiency will becomes so severe that will devellop the inability to produce normal RBCs) 5Microcytic, hypochromic anemia (expanded central pallor)-Bone marrow makes smaller and fewr RBCs and lkess hHb than normal.

What is the laboratory measurement of iron status?

Serum iron-measure of iron in the blood total iron binding capacity (TIBC)- measures of transferrin molecules in the blood that are bound or not. % saturation-percentage of transferrin molecules that are bound by iron (normal is 33%) 4. Serum ferritin-refects iron stores in bone marrow macrophage and the liver

What is the sickle trait?

Sickle trait is the presence of one mutated and one normal ß chain;results in <50% HbS in RBCs (HbA is slightly more efficiently produced than HbS) 1. Generally asymptomatic with no anemia; RBCs with <50% HbS do not sickle in vivo except in the renal medulla i. Extreme hypoxia and hypertonicity of the medulla cause sickling, which resultss in microinfarcation leading to microscopic hematuria, and eventually, decreased ability to concentrate urine.

What is the treatment of chelation therapy?

Succimer, dimercaprol, ethylenediaminetertraacetic acid (EDTA)

What are the basic basic principles of microcytic anemias?

THe best way to look at MCV as a student is the MCV which is the estimate of the size of the RBC. A. anemia with MCV < 80microeter3) B. Microcytic anemia are always due to decreased production of hemoglobin. 1. RBC progenitors cells in the bone marrow are large and normally divide multple times to produce smaller mature cells (MCV=80-100) 2. MIcrocytosis is due to an extra division which occurs to maintain hemoglobin concentration to maintains the cells pretty color. C. Hemoglobin is made of heme and globin; heme is composed of iron and protoporphyrin. A decrease in any of these components leads to microcytic anemia. D. Microcytic anemias include 1) iron deficiency anemia 2) anemia of chronic disease causing the iron to be stored away in macrophages, 3) sideroblastic anemia low protoporhyrin, and 4)thalassemia (decrease producintion of globin chain).

whats a WBC count and differential?

a 100 cell differetnial count divides leukocytes by percentage (neutrophils, lymphocytes) and further subdivides neutrophils into segmented and band neutrophils. Multiplication of the percentage the total WBC count gives the absolute number of a particular leukocuyte. Example lymphocytes 30%, total WBC count 10,000 , absolute luymphocyte count is 0.3X10,000=3000

What is chronic alcoholism?>

a. Alcohol is a mitochondrial toxin (poison). Damages heme biosynthetic pathways in the mitochondria b. Sideroblastic anemia is present in 30% of hospitalized chronic alcoholics.

What is the epidemiology of sideroblastic anemia?

a. Chronic alcholism (most comon cause) b. Puridoxine (vitamine B6) deficiency c. Lead (pb) poisoning d. X linked recessive (XR) disease

Wat his the pathogenesis of ß-THal minor?

a. Decrease ß-globin chain synthesis 1)Mild anemia is most often due to DNA splicing defect 2) Sever anemia is due to a nonsense mutation with formation of a stop codon . Premature temination of ß-globin chain synthesis or absent ß-globin chain synthesis b. Normal synthesis of ∂, delta, and y globin chains c. ß-thal minor 1) mild microcytic anemia 2. decreased MCV, HB, and Hct 3) increased RBC count 4) MCV. RBC count raitio<13 5. Target cells consistenly presnet 6.Teardrop RBCs present due to damge of the RBC membrane from removal of excess globin chains by splenic macrophages 7. Normal RDW, serum ferritin, and srum FEP. Serum FEP is normal because heme synthesis is normal 8Hb electrophoresis a. HbA(2∂/2ß) is decreased ,because ß globin chains are decreased b) corresponding increase in HbA2 and Hbf 9)no treatment

What is the pathogenesis of ACD?

a. Decreased heme synthesis b. Decreased renal production and/or response to EPO c. Increased liver synthesis and release of hepcidin

What is iron distribution of deficiency anemia?

a. Functional iron is present in Hb, enzyes and myglobin. Amount of functional iron in men is 2500 mg and in women 2000 mg. b. Iron is primayly stored as ferritin and hemosiderin in bone marrow macrophages. Amount of stored iron in medn is 1000mg and in women, 400mg (decreased due to menses) c. Total iron stores in men 3500mg , and in women 2400 mg

What is the Laboratory findings in sideroblastic anemias?

a. Increased serum iron iron stauration and ferritin b. Normal to decreases MCV and decreased TIBC c. Ringed sideroblasts in a bone marrow aspirate

What is the Epidemiology of iron deficiency?

a. Most common overall anemia b. Most common nutritional deficiency worlwide c. Greatest prevalence of the anemia is found in 1) toddler aged 1 to 2 years due to inadequate intake of iron 2) females aged 12 to 49 years due to the menstrual loss d. Causes of iron deficiency

When is the percentage of iron form the diet increased and absorbed?

a. Normal menstrulal cycle b. pregnancy and lactation c. Any anemia, reglardless of type. underscores the danger of iron overload, if iron supplements are improperly prescribed

What is the laboratory findings of ACD?

a. Normal to decreased MCV 1. ACD, in some cases, present as normocytic anemia. 2. It is most likelky to present as mcirocytic anemia in the stting of rheumatoid arthritis and Crohns disease b. Decreased serum iron TIbC, and percent iron saturation. c. Increased serum ferritin. D. increased serum FEP, less iron to combine with protoporphyrin to form heme e. ANemia rarely<9g/dl 4. Treatment a. Treat the underlying disease causing the inflammation b. Insome cases, giving EPo increases the Hb concentration c. Hepcidin antagonist (recent treatment modality)

What is the use of pentose phosphate pathway?

a. Synthesizes glutathione (GSH) 1. GSH is an anitioxidant that converts hydrogen peroxide (H202) to water 2) GSH also neutralizes acetminophen free radicals b. H202 is a product of oxidative metabolism in every living cell;therefore this

What is the use of methehemoglobin (metHb) reductase pathway

a. THe heme iron in metHb is oxidized (Fe3+) and it cannot bind 02. bReductase system converts iron back to its ferrous (Fe2+) state so that heme groups can bind 02.

haWt is the use of the Leubering-Rapoport pathway?

a. This pathway synthesizes 2,3-bisphophoglycerate (2,3BPG) b. Pathway is required for shiftin the OBC to the right (release 02 to tissue) 7. Lack human leukocyte antigens (HLAs) on their membranes 8. Fate of senescent RBCs a. Normal Life span is 110 to 120 days in the peripheral blood b. Senescent RBCs are phagocytosed in the cords of Billroth by splenic macrophages. c. Heme degradation by macrophages produce unconjugated bilirubin (UCB). Most of the UCB in blood in a normal individual derives from destruction of senescent RBCs.

What are the stages of iron deficiency

in sequence are as follow: absent iron stores, decreased serum ferritin, decreased serum iron, increased TIBC, and decreased ironsaturation, normocytic normochromic anemia, and microcytic hypochromic anemia.

What is the ∂-trait a diagnosis of exclusion?

Usually there is a fmaily history of members iwth a mild microcytic anemia, normal HB electrophoresis, and normal iron studies. there is no treatment

What is the causes megaloblastic anemia?

1 less division of the erythroblast occurs and this causes the formation of a macrocytic anemia due to the disruption of the production of the DNA precursors, which these precursors are important for DNA divison because there is need of a copy of the nucleus resulting in macrocytic anemia. A. Anemia with MCV>100micrometer3; most commonly due to folate or vitamin B12 deficiency (megaloblastic anemia) B. Folate and vitamin B12 are necessary for synthesis of DNA precursors, which will not only effect the RBCs but other cells in the body that rapidly divide too. 1. FOlate circulates in the serum as methyltetrahydrofolate (methyl THF);removal of the methyl group allows for participation in the synthesis of DNA precursors. 2. Methyl group is transferred to viamin B12 (cobalamin) 3. Vitamin B12 then tranfers it to homocysteine, producing methionine. C. Lack of folate or vitamin B12 impairs synthesis of DNA precursors 1. IMpaired division and enlargement of RBC precurors lead s to megalobastic anemia. 2. Impaired division of granulocytic precursors leads to hypersegmented neutrophils which are greater than 5 lobes, which a neutrophil normally has anywhere from 3-5 lobes. 3. Meggaloblastic change is also seen in rapidly-dividing (intestinal) epithelial cells there are at least seven lobes on the neutrophil and obserrve the bigger RBC on the bottom right that is example of a macroovalocyte and these are classif findings in megaloblastic anemia which are due to folate or vitamin b12 deficiency.

What is the Clinical and laboratory findings of sideroblastic anemia?

1) Abdominal colic with constipation (children), Lead is visible in the gastrointestinal tract on plain abdominal radiographs. 2) Encephalopathy (children a. cerebral edema and pailliedema, lead damages capillary endothelium, causing leakage into the brin parenchyma, lead also damges myelin and inducess demyelination b. Learning disabilities (children) 3) growth retardation (children) a. Lead is deposited in the epiphysis of growing bone b. Radiographs show increased density in the epiphyses 4) Peripheral neuropathy in adults (children to a lesser extent) Example-foot drop (peroneal nerve palsy), wrist drop (radial nerve palsy), and claw hand (ulnar nerve palsy) 5) Nephrotoxic damage to promixal renal tubules (adults). 6) Lead line in the gums , usually occurs in adults who have preexisting gingivitis 7. Reduced RBC survival time (>hemolytic anemia) 8) Increased whole blood and urine lead levels, best screen and confirmatory tests.

HOw is the amount of iron absorbed and regulated?

1. Absorption is dependent of total iron stores in the body, which is reflected by yhr smouny og iron bound to transferrin. 2. Tranferrin with iron binds to transferrin receptors in immature precursor cells of normal enterocytes, which serve as iron sensors in the duodenum. 3. HFE gene (hemochromatosis gene) protein product in the sensor cells acting with the transferrin receptor causes differntiation of these cells into mature enterocytes that absorb iron 4. HFE protein product also regulates the production of hepcidin, a hormon synthesized in the liver. a. Hepcidin is the master iron regulatory hormone and determines whter iron is absorbed or not absorbed in the duodemum and whter iron is released from macrophages or not released b. A decreased level of tranferrin bound iron binding to transferrin receptors in evnertocytes indicates iron deplteion which leads to recdued hepcidin syntehsis in the liver. This upregulates ferroportin 1, causing more iron to be reabsorbed in the duodenum to bin to transferrin and more iron to be released from bone marrow macrophages to bind to transferrin for erythropoiesis c. and increased level of transferrin-bound iron binding to transferrin receptors in enterocytes indicated iron excess, which leads to increased hepcidin synthesis in the liver. THis downregulates ferroportin1, causing iron accumulation int he enterocytes which are eventually shed into the bowel. A reduced level of ferroportin 1 also causes iron blockage in bone marrow macrophages, so less is released for binding tor transerrin.

What is the pathogenesis of microcytic anemias?

1. All are defect in Hb synthesis, Hemoglobin =heme+globin chains 2. Defect in heme synthesis (iron +protoporphyrin)include: Iron deficiency, ACD, and sideroblastic anemias 3Defects in globin chain synthesis (∂ and ß) include ∂ and ß thal

What is the platelet count?

1. Anucleated cells 2. Derived from cytoplasmic budding of megakaryocytes int he bone marrotw. 3. Have human leukocyte anitgeens on their membrane

What are the Hc, HCt, and RBC counts?

1. Factors (age, sex, pregnancy) affecting the normal range 2.Anemia which is a decrease in HB, HCT or RBC concentration b. O2 saturation (Sa02) and Pa02 (partil pressure of arterial Po2) are normal 02 exchange in the lungs is normal;therefore the Pa02 and Sa02 are normal in anemia c. O2 content, which includes the Hb concentration, Sa02, and Pa02, is decreased, because the Hb concentration is decreased d. Anemia is a sign of ynderlying disease rather than a specific diagnosis e. General clinical findings: 1) fatigue, dyspnea with exertion, inability to concetnrate, and dizziness 2)pulmonary valve flow murmur, due to decreased blood viscosity in severe anemia. 3. Pallor of the skin, conjunctivae, and palmar creases. which are indicators of severe anemia. 4. High-putput cardiac failure, due to decreased blood viscosity in sever anemia

What is the reticulocyte and teh reticulocyte count?

1. Importantce of reticulocytes a. Newly released RBCs from the bone marrow b. Peripheral blood markers of effective erythropoiesis c. Effective erythropoiesis refers to a good bone marrow response to anemia Correlates with an increase in synthesis/release of reiculocytes from the bone marrow. 2. Easily identified in the peripheral blood with supreavital stains. Stains detect thread tlike RNA filament in the cytoplasm of young RBCs. 3. In 24 hours, a reticulocyte becomes a mature RBC. maturation occurs with the help of splenic macrophages 4Reticulocyte count is reported as a percentage (normal <3%) a. Using the percentage reticulocyte count in anemia gives a falselye erythro incerasd percentage b. Initial percentage must be corrected for the degre of anemia. C. Corrected reticulocyte count=)actual Hct/45) x reticulocyte count, where 45 represents the normal hematocrit (Hct). D. Example calculation 1) Hct 15%, reticulocyte counte 18% 2) Corrected retciulocyte count is 6% (15/45 x 18%=6&) e. Additional correction isrequired if RBC polychromasia is present 11)polychomatic RBCs are younger than reticulocytes 2) appear in the peripheral blood when there is a very brisk hemolytic anemia 4Falsely increase the intial reticulocyte count, because they RNA filamentts and are counted as "24 hour old" reticulocytes. 5) Correctin for polychromasias is made by dividing the intial reticulocyte count corrected for the degree of anemia by 2. In the pervious example, if polychromasia is present, the additional correctin is 6%/2=3%, which is still a good response to anemia 6) Corrected reticulocyte count >3% a. Represents a good bnoe marrow response to athe anemia (effective erythropoiesis) B. Examples of effective erythopoiesis incldue. Hemolytic anemia (sickle cecll anemai) and the reituclocyte count after treament of iron deficiency with iron 7) corrected reticulocyte counte <3% a. indicates a poor bone amrrow response to anemeia, which is called ineffective erythrooesis b. Examples ineffectiv

What is the Microcytic anemia types?

1. Iron deficiency (most common) 2. Anemia of chroninc disease (ACD) 3. THallassemia (thal;∂ and ß) 4. Sideroblastic anemias (leas common)

What is the characteristic of mature RBCs?

1. Lack mitochondria; therefore there is no citric acid cycole, no ß-oxidation of fatty acids and no ketone body synthesis 2. Lack a n ucleusl therefore they cannot synthesise DNAor RNA. 3. Use anaerobic glycolyssis as their primary source of ATP. Lactic acid is thehesisze ATP (cori cycle). end produce of BC anerobic metabolism b. Lactic acid is converted by the liver into glucose viaglgluconeogenesis c. Glucoose derived from gluconeogenesis is used by RBCs to synthesize ATP

What is the Red blood cell indices?

1. Mean corpuscual volume 2 Mean corpuscular hemoglbin concentration 3. Red blood cell distribution width

What are the laboratory finding of iron defieciency anemia? What syndrome is associated?

1. Microcytic, hypochromic RBCs with increased red blood cell distribution width (RDW) and measures the specturm of size of the RBCs and if there is a wide spectrum due to carying sizes of RBCs that cause the RDW to be high and if all of the RBCs are the same size then the RDW is going to be low and all of this could be due to iron deficiency which causes the bone marorw in its inital phase to produce less RBCs and then progressively make smaller cells or the cells of the erythroblast progenito to divide and extra time due to the deficiency in heme or protoporphyrin.. 2. Decrease ferritin due to the use of the iron stores; increase TIBC; Decrease serum iron and decrease % saturation. 3. increase free erythrocyte protoporphyrin (FEP) and is very high yield and a very good test for iron deficiency anemia, heme consist of iron and protoporphyrin so if the iron is down then some of the protoporphyrin will not be bound to iron and be free in the RBC I. Treatment involves supplemental iron (ferrous sulfate) and if it is an older male then its very important that we rule out colonic carcinoma. J Plummer-Vinson syndrome is iron deficiency anemia with esophageal web (usually the mucosal outfolds that causes a partial obstruction in the esaphagus and when the mucosal comes off the wall of the esophagus) and atrophic glossitis presents as anemia, dysphagia, and beefy-red tongue. RBC should be the size of the nucleus of a lymphocyte and these are small which shows a hypochromic microcytic anemia, which fits the description of a iron deficient anemia.

What is the Normocytic anemia with predominant intravascular hemolysis?

1. Paroxysmal Nocturnal Hemoglobinuria (PNH) 2. GLucose-6-phosphate Dehydrogenase (G6PD) deficiency 3. Immune hemolytic anemia (IHA) 4. Miroangiopathic hemolytic anemia 5. Malaria

What are the iron studies?

1. Serum ferritin a. Def-soluble iron binding storage protein 1. synthesized by bone marrow macrophages and hepatocytes 2) Keeps iron in a non-toxic from 3. Macrophages are the primary storage for ferritin in the bone marrow. b. Most macrophage iron comes from phagocytosis of senescent RBCs. Source macrophage iron:phagocytosis senescent RBCs 4. Serum levels directly correlate with ferritin stores in the macrophages. 1 microgram perliter of serum ferritin correlates with 8 mg of storage iron. Due to the release of interleukin-6 b Decrease in serum ferritin is diagnostic of iron deficiency c. Increase in serum ferritin is present in ACD and iron overload disease. d. Hemosiderin is a insoluble product of ferritin degradation in lysosomes. 1) Decreased and increased levels of hemosiderin correlates with changes in the ferritin stroes in the bone marrow macrophages. 2. Hemosiderin stains blue with prussian blue stain.

What is the laboratory findings of sickle cell?

1. Sickle cells and target cells are seen on blood smear in sickle cell disease, but not in sickle cell trait. 2. Metabisulfite screen causes cells with any amount of HbS to sickle; positive in both disease and trait 3. Hb electrophoresis confirms the presence and amount of HbS. i. Disease-90% HbS, 8%, HbF 2%, HbA2(no HbA) ii. Trait-55% HbA,43% HbS, 2% HbA2

What is the laboratory finding for iron deficiency?

1. decreased MCV 2. Decreaed Serum iron and iron saturation 3. Decreased erum ferritin 4. INcreaes TIBC and RDW 5.Microcytic and normocytic cells are present with increased central area of pallor 6. Increased serum level of free erythrocyte protorphyrin (FEP) less iron to combine with protoporphyrin to form heme. 7. THrombocytosis a. common finding in chronic iron defciency b. Reactive phenomenon to increase blood ciscosity and prevent high output heart failure. 8. WBC count is usually normal. EOsinophilia occurs inhookwork infestations

What is the Laboratory finding of chronic disease?

1. increae ferritin (storage iron cannot be used and it will pile up and be high), decrease TIBC, decrease serum iron (due to the stoarage of iron no being able to be used then the serum iron will be used) and decrease % saturation. 2 increase free erythrocyte protoporphyrin (FEP) due to the decrease in Fe in the early phase of chronic diesease the body produces normocytic anemia and then as the disease becomes severe the patient can devlop microcytic anemia D. Treatment involves addressing the underlying cause that causes a decrease in the inflammation that will decrease the amont of hepcidin and free the iron that is being held to the bone marrow. ALSO, exogenous EPO is useful in a subset of patients, espcieally those with cancer. one of the effects of hepcidin is blocking Erthopoetin.

What is the iron transferred in sideroblastic anemia?

Iron is transferred erythroid precursor and enters the mitochondria to from heme. If protoporphyrin is deficient, iron remains trapped in mitochondria. 1. Iron-laden mitochondria form a ring around the nucleus of erythroid precursors (generally mitochondria are found around the nucleus); these cells are called ringed sideroblasts ( hence, the term sideroblastic anemia)

What is ß thalassemia minor?

2. ß-Thalassemia minor (ß/ß+ decrease production of beta) is the mildest form of disease and is usually asymptomatic with an increased RBC count and a microcytic hypochromic anemia with target cells i. Microcytic, hypochromic RBCs and target cells ,which are RBCs which normally have hemoglobin on the outside of the biconcave RBC due to the thicker edges of the RBC and small amounts of hb are seen in the region of central pallor and its thinner but due to its lighter shade it does not contain as much Hb as the outside of the RBC, a target cell is a RBC that has darker area in the central of the central pallor due to the membrane blebbing that causes the hemoglobin to go into the enter of the RBC. Target cells are due to decrease in Hb cytoplasms, or an increase in the amount of Hb in themembrane. and these are seen on blood smear. ii. Hemoglobin electrophoresis shows slightly decreased HbA with isolated increased HbA2 which is the key finding(5% , normal 2.5%) and HbF(2%, normal 1%).

What is the aplastic anemia?

A. Damage to heamtopoietic stem cells, resulting in pancytonpenia (anemia, thrombocytopenia, and leukopenia) with low reticulocyte count B. Etiologies include drugs or chemicals, virla incections, adn autoimmune damage C. Biopsy reveals an empty , fatty marrow. D. Treatment includes cessation of any causative drugs and supportive care with transfusions and marrow stimulating factors (erythropoietin, GM-CSF, and G-CSF) 1. Immunosuppressin may be helpful as some idopathic cases are due to abnormal T-cell activation with release of cytokines. 2> May require bone marrow transplantation as a last resort.

What is the Paroxysmal nocturnal Hemoglobinuria (PNH)?

A. Acquired defect in myeloid stem cells resulting in absent glycosylphosphatidylinositol (GPI) will not be present in all of the cells fro the myeloid lineage; renders cells susceptible to destruction by complement 1. Blood cells coexist with complemet 2. Decay accelerating factor (DAF) on the surface of blood cells protect against complement-mediated damage by inhibiting C3 convertase. 3. DAF is secreted to the cell membrane by GPI (an anchoring glycolipid)] and MIRL can also inactivate complement and connected to the RBC membrane by a anchoring protein called GPI. 4.Absence of GPI leads to absence of DAF, rendering cells susceptible to complement-mediated damage. B. Intravascular hemolysis occurs episodically, often at night during sleep. 1. Mild respiratory acidosis develops with shallow breathing during sleep and activates complement, and patients with normal RBCs, platelets, and Leukocytes are protected against this activation. 2. Patients with absent GPI will have RB, WBCs and platelets are lysed. 3. Intravascular hemolysis leads to hemoglobinemia and hemoglobinuria (especially in the morning); Hemosiderinuria is seen days after hemolysis .C. Sucrose test is used to screen for disease; confirmatory test is the acidified serum test or flow cytometry to detect lack of CD55 (DAF) that uses GPI as a linker molecule on blood cells D. Main cause of death is thrombosis of the hepatic, portal or cerebral veins 1. Destroyed platelets release cytoplasmic contents into circulation that can activate the coagulation cascade, inducing thrombosis E. Complications include iron deficiency anemia (due to chronic loss of hemoglobin in the urine) and acute myeloid leukemia (AML) due to mutation in the myeloid stem cell, and its not hard to get another mutation, which develops in 10% of patients.

What is erythropoiesis?

A. Aerythropoiesis and erythropoietin a. Production of RBC in the bone marrow b. Dpeendent on the relase of erythropoietin (EPO) form the kidneys 2. EPO synthesized in the renal cortex interstital cells in the peritubular capillary bed. E. Stimuli for EPO release include: Hypoxemia (decrease P02), severe anemia, left-shifted O2 binding curve (OBC),high altitude, and decreased O2 saturation (Sa02;carbon monoxide poisoning, methemeoglobinemia) 4. Increased O2 content suppresses EPO release (polycythemia vera). 5. Other sources of EPO. Ectopically produced in renal cell carinoma, and hepatocellual carinoma.

What is the anemia of chronic disease?

A. Anemia associated with chronic inflammation ( endocarditis, or autoimmune conditions) or cancer; most common type of anemia in hospitalized patientss. B. Chronic disease results in production of acute phase reactants from the liver including hepcidin. 1. Hepcidin sequesters iron (preventing iron from being transferred to together cells)in storage sites by 1) limiting iron transfer from macrophages to erythroid precursors, and 2) suppressing erythropoietin (EPO) production that suppresses the drive of the bone marrow to make RBCs; aim is to prevent bacteria from accessing iron, which is necessary fro their survival becuase the body does not know how to distinguish between autoimmune inflammation, or a cancer associated with the inflammation. 2. Decrease available iron then leads to decrease heme and then decrease hemoglobin and then microcytic anemia.

What is the Thalassemia?

A. Anemia due to decreased synthesis of the globin chains of hemoglobin 1. decrease globin then decrease hemoglobin then microcytic anemia. B. inherited mutation; carriers are protected against plasmodium falciparum malaria C. Divided into ∂ and ß-thalassemia based on decreased production of alpha or beta globin chains. 2.Normal types of hemoglobin are HbF (∂2y2), HbA (∂2ß2), and HbA2, and all copies have an alpha, so there are four copies of the alpha gene

What is the sideroblastic anemia?

A. Anemia due to defective protoporphyrin synthesis 1. decrease protoporphyrin leads to decrease heme and then decreased hemoglobin and then microcytic anemia B. Protopohyrin is synthesized via a series of reactions. 1. AMinolevulinic acid synthetase (ALAS) converts succinyl CoA to aminolevulinic acid (ALA) using vitamin B6 as a cofactor (rate-limiting step) 2. AMinolevulinic acid dehydratase (ALAD) converts ALA to porphobilinogen 3. Additional reaction convert porphobilogen to protoporphyrin 4. Ferrochelatase attaches protoporphyrin to iron to make heme (final reaction; occurs in the mitochondria)

What is the normocytic anemia?

A. Anemia with normal sized RBCs (MCV=80-100). B. Due to increased peripheral destruction (outside of the bone marrow) or underproduction (not producing enough RBCs in the red bone marrow) 1. Reticulocytes (are young RBC that are relased from the RBM) count helps to distinguish between these two etiologies

What is the immune hemolytic anemia (IHA)?

A. Antibody-mediated (igG or IgM) desruciton of RBCS B. IgG-mediated disease usually involves extravascular hemolysis 1. IgG binds RBCs in the relatively warm temperature of the central body (warm agglutinin); membrane of antibody-caoted RBC is consumed by splenic macrophages by slowly nibbling off pieces of the membrane, resulting in spherocytes. 2. Associated with SLE (most common cause due to the fact that you can antibodies against Red cells, White cells and platelets), CLL, adn certain drugs that some can attach to RBC embrane and then the anitbody will bind the drug membrane complex and then the macrophags of the spleen will remove or the drug induces anitbodies it self (calsccaly, binding of antibody to drugs membrane complex ii. Drugs may induce production of autoantibodies (methyldopa) that bind self antigens on RBCs 3Treatment involves cessation of the offending drug, steriods, IVIG spleninc macrogaes iwill IVIG instead of the antibody complex of concern, and if necessary, splenectomy.

What is the hemoglobin C?

A. Autosomal recessive mutation in ß chain of hemoglobin 1. Normal glutamic acid is replaced by lysine. 2. Less common than sickle cell disease. b> Presents with mild anemia due to extravacular hemolysis C. characteristc HbC crystals are seen in RBCs on blood smear.

What is sickle cell anemia?

A. Autosomal recessive mutation in ß-chain of hemoglobin; a single amino acid change replaces normal glutamic acid (hydrophilic )with valine (hydrophobic). B. Gene is carried by 10% of individuals of African descent, likely due to protective role against falciparum malaria. C. Sickle cell disease arises when two abnormal ß genes are present; results in >90% HbS in RBCs. D. HbS polymerizes when deoxygenated and its reversible; polymers aggregate into needle-like structures, resulting in sickle cells. 1. Increased risk of sickling occurs with hypoxemia, dehydration and acidosis. 2.HbF protects against sikcling, high HbF at birth is protective for the first few months of life. Treatment with hydroxyurea increases levels of HbF.

What is the folate deficiency macrocytic anemia?

A. Dietary folate is obtained from green vegetables and some fruits. 1. Absorbed in the jejunum B. Folate deficiency develops within months, as body stores are minimal C. causes include poor diet (alcoholic and elderly), increased demand (pregnancy the cell of the baby has DNA, cancer (is generating cells with nuclear material), and hemolytic anemia (patients are rapidly turning over therir RBCs), and folate antagonist (methotrexate which inhibits dihydrofolate reductase) and these things can result in a folate deficiency. D. Clinical and laboratory finding include 1. Macrocytic RBCs (MCV greater than 100) and hypersegmented neutrophils (>5lobes) 2. Glossitis ( inflammation of the tongue and has to due to the fact that cells of the tongue arent turning over as fast) 3. Decrease serum folate 4. Increase serum homocysteine due to lack of folate or B12 and this prevents the production of methionine (homocysteine) increases risk for thrombosis) 5. Normal methylmalonic acid, which gets converted to succinyl CoA and the mechanism is by vitamin B12, and in patients with foflate deficiency these acid will be normal and help distinguish between b12 and folate deficiency in deciding which megaloblastic anemia that could be the root cause.

What is the peripheral RBC destruction (Hemolysis)? WHat are some clinical signs of each? What can you observe in the urine?

A. Divided into extravascular and intravascular hemolysis both result in anemia with a good marrow response of greater than 3%. B.Extravascular hemolysis involves RBC destruction by the reticuloendothelial system (macophages of the spleen, Liver, and lymph nodes). 1. macrophages consume RBCs and break down hemoglobin i. Globin is broken down into amino acids ii. Heme is broken down into iron and protoporphyrin; iron is recycled. ii. Heme is broken down into iron and protoprophyrin; iron is recycled. iii. Protoporphyrin is broken down into unconjugated billirubin, which is bound to serum albumin and delivered to the liver for conjugation and excretion into bile it is not water soluble it is fat soluble and it will remain in the serum until the liver can take it and conjugate it and then put it into the bile. 2. Clinical and laboratory finding include i. Anemia ( because they are destoryoing RBCs) with splenomegaly(becuase the spleen is consuming RBCs and this is an example of hypertrophy), jaundice due to unconjugated billirubin due to the increase load that the liver can handleand this also will cause the liver to conjugate the billirubinand cause a a supersturation of UCB in the bile, and increased risk for bilirubin gallstones. ii. Marrow hyperplasia with corrected reticulocyte count >3%. C. Intravascular hemolysis involves destruction of RBCs within blood vessels and this causes Hb to go directly into the blood and to be bound with a molecule called haptoglobin and this molecule takes the Hb to the spleen to be reprocessed to save Hemoglobin and to save Iron awwhich is hard ot get ahold of and the Haptoglobin levels will decrease. 1. Clinical and laboratory findings include i. Hemoglobinemia. ii. Hemoglobinuria iii. Hemosiderinuria- several days later, Renal tubular cells pick up some of the hemoglobin and it will be destroyed and filtered from the urine and broken down into iron and heme, and the iron will acumulate as hemosiderin; tubular cells are eventually shed ecuase of turning over and resulting in hemosiderinuria. iv. Decreased serum haptoglobin which is the very inital change of intravascular hemolysis

What is iron deficiency anemia? How is it transported? What are the types of iron?

A. Due to decreaed levels of iron 1. decrease iron leads to decrease heme leads to decrease hemoglobin and leads to microcytic anemia B. Most common type of anemia. 1. Lack of iron is the most common type of nutritional deficiency in the world, affecting roughly 1/3 of world's population. C. Iron is consumed in heme (meat-derived) and non-heme (vegetable-derived) forms. 1. Absorption occurs in the duodenum. Enterocytes have heme (Heme carrier portein 1) and non-heme (DMT1 converts Fe3+ into the Fe2+) transporters; the heme form is more readily absorbed and the absorption occur in the duodenum. 2. Enterocytes takes up iron from the lumen of the gut and makes a decision to transports iron across cell membrane into blood via ferroportin bu thte body has no way to get rid of iron and a little of the iron gets lost when the skin is sloghin goff and a female may lose iron throuhg the menstraul cycle but generally we can not get rid of iron and the enterocyte plays a major role in deciding whether iron needs to go into the blood.., Iron is always bound because it has the ability to generate free radicals. 3. Transferrin (for every 3 transferrin moecules 1 will be carrrying iron) transports iron in the blood and delivers it to liver and bone marrow macrophages for storage. 4. Stored intracellular iron is bound to ferritin, which prevents iron from forming free radicals via the Fenton reaction.

What is malaria? and Normoacyctic anemia>

A. Infection of RBCs and liver with plasmodium transmitted by the female anopheles mosquito. B. RBCs rupture as a part of the plasmodium life cycle, resulting in intravascular hemolysis and cyclical fever 1. P falciparum-daily fever 2. P vivax and Povale-fever every other day C. Spleen also consumes some infected RBCs; results in mild extravascular hemolysis with splenmegaly look at the fragments of the organism in the RBC

What is Parvovirus B19 anemia caused by underproduction?

A. Infects progeitor red cells and temporatily halts erythropoiesis; leads to significant anemia in the setting of preexisting marrow stress (sickle cell anemia) B. Treatmetn is supportive (iinfection is self-limited)

What is the Hereditary spherocytosis? How do they appear on histo? What are the comomn mutations in? What increases? How do you treat?

A. Inherited defect of RBC cytoskeleton-membrane tethering proteins that allows the cytoskelton to keep the shape of the cell membrnae and when these cytoskeleton membrane molecules are mutated or lost then this causes little blebbing of the [memebrane and the macrophages of the speen remove these blebs (i think!) and this cause s a loss of membrane on the RBC tahat causes it to lose its shape and it becomes a sphere 1. Most commonly involves ankyrin, spectrin, or band 3.1 B. Membrane blebs are formed and lost over time 1. Loss of membrane renders cells round (spherocytes) instead of disc shaped. 2. When the Spherocytes becomes so small due to the loss of membrane then they are less able to manuever through splenic sinusoids are consumed by splenic macrophages, resulting in anemia. C. Clinical and laboratory finding include 1. Spherocytes with loss of central pallor 2. Increase RDW and Increase mean corpuscular hemoglobin concentrations (MCHC), so as you shrink down the cell the cytoplasm remains about the same so the hemoglobin becomes more concentrated in the cell. (the only other disease that there is an increase MCHC is autoimmune anemia, and there is a similar process and also the production of spherocytes) 3. Splenomegaly (which is a work hypertphy and the macophage will undego hypertophy as they eat away at the RBCs.), jaundice with unconjugated billirubin, and increased risk for bilirubin gallstones (extravascular hemolysis) 4. increased risk for aplastic crisis with parvovirus B19 infection of erythroid precursors. D. Diagnosed by osmotic fragility test, which reveals increased spherocyte fragility in hypotonic solution this will cause water to go into the cell and its biconcava shape has enough membrane for the water to enter the cell without bursting, but if its already a spherocyte then the cell wil burst. 3. Treatment is splentectomy because there are no porblems having spherocytes its just the spleen eats them due to the shape; anemia resolves, but spherocytes persist because the cells still have a problem with membrane blebbing and the cells will still go through the reticuloendothelial system and the blebs and membrane will be removed and Howell-Jolly bodies (fragments of nuclear material in RbCs and its the job of the spleen to remove this nuclear material, but if the spleen is removeed then ) emerge on blood smear Loss of central Pallor due to the non biconcave shape and the RBC are spheres but they also are differentis ce sizes due to the RBCs losing membrane, so the oldest celthls will have lost the most membrane and youngest cells will have lost the least.

What are the basic principles of anemia? What about in a pregnant women and a gunshot victim?

A. Reduction in circulating RBC mass B. Presents with signs and symptoms of hypoxia due to the decrease in the oxygen being carried by Hb 1. Weakness, fatigue and dyspnea 2. Pale conjunctiva (relatively good sign of anemia) and skin 3. Headache and lightheadedness due to hypoxia to the CNS. 4. Angina due to low o2 in the blood which equates to low delivery to the heart, especially with preexisting coronary artery disease a woman may have normal RBC mass when shes pregnant but because her blood volume increases so much her Hb, and Hct go down, but this does not indicate a decrease in RBC mass but she has more blood volume and has diluted out her normal RBC mass. or antoher example a patient has a gunshot wound and the patient will bleed out both RBC and fluid, but immediately after the gunshot wound when theres blood loss the patients Hb and HCT will be normal, but you will see that there is blood loss when you give fluid or when the paients gets fluid back into their system there will be a dilution of the remaining RBCs and that result in a decreae in Hb and HCt. Each of the surrogates are concentration dependent and could not be a good indicator of RBC mass in some circumstances. C. Hemoglobin (Hb) , hematocrit (Hct), and RBC count are used as surrogates to help determine what RBC mass would be, which is difficult to measure. D. Based on mean corpuscular volume (MCV), anemia can be classified as microcytic (MCV <80 micrometer3), normocytic (MCV=80-100micrometer3), or macrocytic (MCV>100 micrometer3)

What is the glucose-6-phophsta dehydrogenase (G6PD) Deficiency?

A. X-linked recessive disorder resulting in reduced half-life of G6PD; renders cells susceptible to oxidative stress. 1. RBCs are normally exposed to oxidative stress, in particular H2O2 2. Glutathione (an antioxidant) neutralizes H202, but becomes oxidized in the process. 3 NADPH, a by-product of G6PD, is needed to regenerate reduced glutathione. 4. Decrease G6PD then decrease NADPH and then Decrease reduced glutathione and then oxidative injury by H202 and then intravascular hemolysis. so basically H202 is oxidized by GSh but inorder to rduce glutathione back the NADPH moecule is needed and this molecule is synthesized from G6PD, so in defiecincy this doesnt allow glutathione to prtoect the cells from oxidative satress. B. G6PD deficiency has two major variants (in a nomral patient the GP6D will last the life of the entire RBC) 1. African variant-mildly reduced half-life of G6PD leading to mild intravascular hemolysis with oxidative stress, so only the older wont have GP6d. 2. Mediterranean variant- Markedly reduced half-life of G6PD leading to marked intravascular hemolysis with oxidative stress, which means some of the younger cells will be destroyed due to lack of G6PD. 3. High carrier frequency in both populations is likely due to protective role against falciparum malaria. C Oxidative stress precipitates Hb as Heinz bodies 1. Causes of oxidative stress include infections, drugs (primaquine, sulfa drgus, and dapsone) and fava beans. 2. Heinz bodies are removed from RBCs by splenic macrophages, resulting in bite cells 3. Leads to predominantly intravascular hemolysis D. Presents with hemoglobinuria and back pain becausehemoglobin is nephrotoxic hours after exposure to oxidative stress E. Heinz preparation is used to screen for disease (precipitated hemoglobin can only be seen with a special Heinz stain) enzyme studies confirm deficiency (performed weeks after hemolytic episode resolves.)

What are the reticulocytes in normocytic anemia>

A. Young RBCs released from the bone marrow 1. Identitified on blood smear as larger cells with bluish cytoplasm (due to residual RNA), basically when the RBC is born the nonucleus and has most of its hemoglobin but there is some redisual processing of RNA and prtoein synthesis in the first day or so after birth. B. Normal reticulocyte count (RC) in the blood smear is 1-2% and each day roughly 1-2% of cells are removed form circulation and replaced by reticulocytes C. A properly functioning bone marrow respond to anemia by increasing the RC to >3% D. RC, however, is falsely elevated in anemia for example if the percentage of RBC is 98 and 2 percent are RC theen if an anemia occurs then it will be 48% and th RC remians th same then the reticulocyte count woul be 4% but the number actually didnt change, so it makes it appear as if the bnoe marrow is making RC. 1. RC is measured as percentage of total RBCs; decrease in total RBCs falsely elevates percentage of reticulocytes. E. RC is corrected by multiplying reticulocyte count by Hct/45/ 1. Corrected count>3% indicates good marrow response and suggests peripheral destruction. 2. Corrected count <3% indicates poor marrow response and suggests underproduction this is very important when considering whether the normcytic nanemia is producing blood vessels insiide of the bone marrow being destroyed outisde of the bone marrow.

How does anemia due to underproduction?

A. decreased production of RBCs by bone marrow; characterized by low corrected reticulocyte count B. Etiologies include 1. Causes of microcytic and macrocytic anemia 2. Renal failure-decreased production of EPO by peritubular intersitial cells 3. Damage to bone marrow precursor cells (may result in anemia or pancytopenia)

WHat is the mean corpuscular hemoglobin concentration?

Average Hb concentration in RBCs b. Decreased MCHC 1. Decrease correlates with decreased synthesis of Hb, which is a feature of all the microcytic anemia (iron deficiency) 2.Central area of pallor is greater than normal, because there is less Hb in the cell. called hypochromasia. c. Increased mean corpuscular hemoglobin concentration 1. correlates with the presence of spherical RBCs, which occurs in hereiditary spherocytosis 2. Spherocytes lack the central area of pallor, which is called hyper chromasia.

What is the mean corpuscular volume?

Average volume of RBCs b. Frequently used to classify anemia 1)microcytic anemia:MCV <80 2) Normocytic anemia 3. Macrocytic anemia

What is the congenital and acquired sideroblastic anemia? What vitamin deficiency?

D. Sideroblastic anemia can be congenital or acquired 1. Congenital defect most commonly involves ALAS (rate-limiting enzyme). 2. Acquired causes incldue i. Alcoholism-mitochondrial poison and damages the production of protoprophrin ii. Lead poisoning- inhibits ALAD decrease protporhyrin and ferrochelatase links protporphyrin with iron. iii Vitamin B6 deficiency- required cofactor for ALAS; most commonly seen as a side effect of isoniazid treatent for tubercuosis. E. Laboatory findings include (iron overloaded state) increase ferritin, decrease TIBC< increase serum iron, and increase % saturation (iron-overloaded state), which when it forms the sideoblastic ring in the cell it causes the fenton reaction (basiccaly im dsayin free radicals right?) that damages the cell and causes the cell to die and cause the Fe to lead out and the bone marrow macrophages will eat the iron and cause an increase stores in the macrophages. HEMOCHROMATOSIS which is a condition in which the patient has a iron overloaed state,.... shares the same laboratory findings

What are the other causes of macrocytic anemia?

D. other causes of macrocytic anemia (without megalobasltic change)include alcoholism, livedisae and drugs (5-FU). we would see large RBC, without hypersegmentted neutrophils and megaloblastic change in other rapidly

What is thalassemia? (thal)

Decrease in ∂ or ß globin chain synthesis b. autosomal recessive disorders c. ∂. thal is common in Southeast Asians, people hwo live on the African west coast, and in blacks (prevalence of 5%) d. ß-thal is common blacks, Greeks (prevalence 15% to 30%), and Italians

What is the Pathogenesis of ∂-thal?

Decrease in ∂-globin chain synthesis is due to gene deltions. Fou genes control ∂-globin chain syntehsis b. One gene deltion produces a silent carrier that is not associated with anemia c. Combination of two genes deletions is called alpha-thal trait. 1 Produces a mild anemia with a normal to increasded RBC count. There is no consesnus as to why the RBC is normal to increased, whetn the Hb and Hct are decreased, however, it is a very useful clinical findings. 1. In the black population, it is associate with a loss of one gene of each chromosome 3) in southeast asian population, it is associated with a loss of both genes on the same chromsome. increased risk for devloping more sever types of ∂-thal because one chromsome completely lacks ∂-globin genes.

s What ithe pathogenesis of iron deficiency?

Decreased synthesis of heme (iron +protoporphyrin) leads to a decreased syntehsis of Hb a. Chronic iron deficiency 1. Esophageal web (plummers-Vinson syndrome). Produces dysphagia for solids but not liquids. 2. Achlorhydria, due to the absence of hydrochloric acid in the stomach 3. Glossitis and angular cheilosis. Inflammation of the tongue and corner of the mouth respectfully. 4. Spoon nails (koilonychia) b. Pallor of the conjuctivae and palmar skin creases c. Craving (pica) for ice.

What is the pathogenesis of sideroblastic anemia?

Defect in heme synthesis within the mitochondria of devloping RBCs in teh bone marrow 1) Heme is end product of porphyrin syntehsis 2) heme has a negative relatioship with∫-aminolevulinic acid synthase. b. Iron accumulates in mitochondria which produces ringes ideroblast c. it is classified as a\iron overload type of anemia 1) Iron stores increase markley in the bone marrow macrophages 2 Sideoblasts die in the marrow (ineffective erythropoiesis. Phagocytosed by macrophages, whch leads to excess iron sotores

What Does extensive sickling lead to?

Extensive sickling leads to complication of vaso-occlusions that clead to infarcted tissuesan 1. Dactylitis-swlollen hands and feet due to vaso-occulsive infarcts in bones common presenting sign in infants (commobly show pictures of african american babies that is commonly seen in 6 month year old infants) 2. Autosplenectomy due to vasoocclussive infacrction and its disappears, shrunken, fibrotic spleen. Consequences include that spleen is the primary cource of antibodies so i. Increased risk of incfection with encapsulated organisms such as streptococcus pneumoniae and Haemophilus influenae (most common cuase of death in children); afffected children should be vaccinated by 5 years of age. ii. Increased risk of Salmonella paratyphi osteomyelitis (the most common cuase of osteomyelitis overall is S. Aurues) Howell-jolly bodies on blood smear due to the removal of the spllen the RBC will have nuclear material 3. Acute chest syndrome-vaso-occlusion in pulmonary microcirculation i. Presents with chest pain, shortness of breath, and lung infiltrates ii. Often precipitated by pneumonia causes vasodilation and causes the blood to slow and this increases the transit time which increase dehydration, acedemia, increase deoxygenation that promotes sickling. iii. Most common cause of death in adult patients. 4. Pain crisis 5.Renal paillary necrosis-results in gross hematuria and proteinuria due to a vasoocclusive crisis.

Whats the gender value of anemia in females and males?

Hb< 13.5 g/dl males Hb<12.5 g/dl in females

What is the combination of three gene deletion called?

HbH (four ß-chains) disease 1. Associated with severe hemolytic anemia, excess ∂-chain inclusions cause macrophage destruction of RBCs (hemolytic anemia). 2) Hb electrophoresis detects HbH e. Combination of four genes deletions is called Hb Bart (four y-chains) disease 1)this combination is incompatible with life. 2) Hb electrophoresis shows an increase in Hb Bart. f. Laboratory finding in ∂-thal trait 1)decreased MCV, Hb, and Hct 2. INcreased RBC count MCV/RBC count ratio<13 4.Rarget cells inconsistenly presnet 5. Tear drop RBCs incosistenly prsent 6. Normal RDW, serum ferritin, serum FEP and Hb electrophoresis

how does hb in electrophoresis?

Hemoglobin electrophoresis is normal in alpha thal trait because all Hb types require alpha globin chain. the Hb concentration is decreased however the relative proportions of the normal Hb remains the same.

What are the Normocytic anemia with predominant extravascular hemolysis?

Hereditary spherocytosis Sickle cell anemia Hemoglobin C

Where does hematopoeisis happen in the fetus?

INthe fetus, hematopoeisis begins in the yolk sac and subsequently moves to the liver and finally the bone marrow by the the fifth to sixth month of gestation

What is the IgM disease involved with?

IgM-mediated disease also usually involves intravascular hemolysis 1. IgM binds RBCs and fixes complement in the relatively cold temperature of the extremities like the fingers and the toes (cold agglutinin) 2. RBCs inactivate complement, but residual C3b serves as an opsonin for splenic macrophages resulting in spherocytes; extreme activation of complement canlead to intravascular hemolysis 3. Associated with Mycoplasma pneumoniae and infectious mononuccleosis D. Coombs test is used to diagnose IHA;testing can be direct or indirect RBCs (do I have RBCs already bound by IgG?). When anti-TgG/COmplement is added to patient RBCs, agglutination occurs if RBCs are already coated with IgG or complement. THis is the most importatn test for IHA. 2. Indirect Coombs test confirms the presence of antibodies in patients serum (are there anitbodies in the serum?). Anti-IgG and test RBCs are mixed with the patient serum; agglutination occurs if serum antibodies are present.

What is EPO?

Increases the O2 carrying capacity of blood by stimulating erythroid stem cells to divide (RBC hyperplasia) . Epoetin alfa, a form of EPO propoiduced by recombinant DNA technology, is frequently abused by athletes to increase their energy level. It also is used in the treatment of anemia associated with renal failure, chronic disease, and chemotherapy.

What is the Iron saturation?

Percentage of binding sites on transferrin that are occupied by iron 1) formula for calculating iron saturation: Iron saturation (%)=serum iron/ TIBCx100 bdecreased iron saturation is present in iron deficiency and ACD c. Increasesd iron saturation is present in iron overload diseases

What is extramedullary hematopoiesis (EMH)?

RbC, white blood cell, and platelet production that occurs outside the confindes of the bone marrow 2. Common sites for EMH are the liver and spleen 3. Pathogenesis a. INtrinsic bone marrow disease (myelofibrosis) Baccelerated erythropoeisis (severe hemolysis in sickle cell anemia) 2) THe process expands the bone marrow cavity 2) Radiograph of the skull shows a "hair-on-end" appearance, due to expansion of the bone marrow within the skull bones. 4 EMH procuces hepatosplenomegaly

What is fanconi syndrome?

Tubular damage by lead causes Fanconi syndrome. THe syndrome inclludes promimal renal rubular acidosis (loss of bicarbonare in urine) aminoaciduria, pasphaturia, and glucosuria.

How does pyridoxin deficiency contribute to sideroblastic anemia?

a. Vitamin B6 is a cofactor for ∫-aminoloevulinic acid synthase, the rate limiting reactin of heme synthesis b. Most common cuase of defciency is isoniazid (INH) therapy for TB. INH inactivates pyridoxine 5. Lead (pb) poisoning a. EPidemiology 1)most common in choldren ages 1 to 5 years old 2) May occur in utero, becaseu it crosses the placenta 3. Uncommon cauase of sideroblastic anemia 4) Cuases of lead poisoning a. Pico (abonrmal craving) for eatin Common cuase of childhood lead poisoning in inner cities where there are apartmetns build before 1950, when lead based paints were primarly used. Lead based paints are primarily used for painignt the exterior of homes. b. Pottery glazes that are used commerically or are homemade 5. Working in a batetery or ammunition factory 6) radiators repair mechanics 7. air contamination from a smelter (form of extrative metallurgy) 8 other sources of lead incldude jewlry, moonshine, tradtional medicines (chinese tea), lead plmbing, and imported toys China)

What is Vitamin B12 Deficiency?

this vitamin is found on meat derived proteins such as meat and eggs and comes into the body attach to this proteins. A. Dietary vitamin b12 is complexed to animal derived proteins. 1. Salivary gland enzymes (amylase) liberate vitamin B12, which is then by R binder (also from the salivary gland) and carried through the stomach. 2. Pancreatic proteases in the duodenum detach vitamin B12 from R binder. 3.Vitamin b12 binds intrinsic factor (made by gastric parietal cells) in the small bowel; the intrinsic factor-vitamin B12 complex is absorbed in the terminal ileum. B. Vitamin B12 deficiency is less common than folate deficiency and take years to develop due to large hepatic stores of vitamin B12. C. Pernicious anemia is the most common cause of vitamin B12 deficiency. 1. most common cuase of pernicous anemia Autoimmune destruction of parietal cells (body of stomach which function in 3 P's that have proton pump, they are pink and chief are blue, and pernicous anemia) leads to intrinsic factor D. Other causes of vitamin B12 deficiency include pancreatic insufficiency due to the inabilty to release the B12 from the R binder and damage to the terminal ileum (Crohn disease or Diphylobothrium latum)(fish tapeworm); Dietary deficiency is rare, except in vegan. E. Clinical and laboratory finding include 1. Macrocytic RBCs with hypersegmented neutrophils 2. Glossitis ( ooer turnover to the cells of the tongue) 3. Subacute combined degeneration of the spinal cords (There are two reactions that involve B12; reaction the syntheesis of DNA precursores and the seond is conversion of malonic acid to sucicinyl Coa and if vitamin B12 is lackin gthis will cause a buildup of malonic acid and will build up within the myelin of the spinal cord and will cause degeneration and this will not be seen in folate deficency) i. Vitamin B12 is a cofactor for the conversion of methylmalonic acid succinyl CoA (important in fatty acid metabolism) ii. Vitamin B12 deficiency results in increased levels of methylmalonic acid to succinyl CoA (important in fatty acid metabolism) iii. Damage results in poor proprioception and vibratory sensation (posterior column) and spastic paresis (lateal corticospinal tract) 4. Decreased serum vitamin B12 5. Increase serum homocysteine (similar to folate deficiency, which increases risk for thrombosis. 6. Increase methylmalonic acid (unlike folate deficiency)

What is the ß-Thalassemia Major? What infection is of a major concern? What is the concern of transfusions? What will you see on histo?

ß-Thalassemia Major (ß˚/ß˚) is the most severe form of disease and presents with severe anemia a few moths after birth because during birth the ß chain is not being used in the fetal hemoglobin; high HbF (∂2y2) at birth is temporarily protective so it will take a few months to develop. i. unpaired ∂ chains dimerized and precipitate and damage RBC membrane as they are being generated, resulting in ineffective erythropoiesis and even if the RBC manages to get out of the bone marrow the spleen will recognize the damaged RBC and cause extravascular hemolysis within the splenic macrophages (removal of circulating RBCs by the spleen) ii. Usually erythropoisesis and hematopoeisis in particular erythropoeisis occurs in the central skeleton but when a bbaby is born both of these process wll be present throughout most of the skeleton but as the baby grows the erythropoiesis is limited to the central skeleton, but since theres is severe anemia there will be massive amounts of erythropoietin being release by the kidney and will drive the bone marrow to undergo hyperplasia. Massive erythroid hyperplasia ensues resulting in 1) expansion hematopoiesis into the skull (reactive bone formation lead to 'crewcut' appearance on xray) and facial bones (chipmunk facies) 2) extramedullary hematopoiesis with hepatosplenomegaly due to their production in RBCs and 3) risk of aplastic crisis with parvovirus B19 infection of erythroid precursors...due to the fact that these patients are dependent on every RBC that produce by the bone marrow and extramedullary hematopoeisis.and the parvovirus infects erythroid precursors and shuts them down. Is self limiting infection that only lasts for 1 to 2 weeks and in a normal patent it down not effect them because we have a tremendous reserve but ß thalassemia major patients are so dependent on every RBC that they cant risk shuttin g down for a day and this will create an aplastic crisis. iii. Chronic transfusions are often necessary; leads to risk for secondary hemochromatosis due to the bag of blood is really a bag of iron because those blood cells are being broken down and that iron is being present in the body and the body has no way to get rid of iron. ic. Smear shows microcytic, hypochromic RBCs with target cells and nucleated red blood cells because the RBCs are being made outside of the bone marrow in the liver or the spleen then some of the RBCs can escape the and remain nucleated. v. Electrophoresis shows HBa2 and HbF with little or no HbA.

What types of mutations can cause ß-thalassemia?

ß-Thalassemia is usually due to gene mutations (point mutations in promoter or spliciing sites); seen in individual of African and Mediterranean descent. 1. Two ß genes are present on chromosome 11; mutations results in absent (ßo) or diminished (ß+) production of the ß-globin chain. (ß˚ complete knock out /ß+ decrease production of beta)

What type genes is Thalassemia?

∂-Thalassemia is usually due to gene deletion: normally, 4 alpha genes are present on chromosome 16, 2 on each chromosome. 1. One gene deleted-asymptomatic 2. Two genes deleted-mild anemia with increase RBC count; if the deletion is trans its not something that is noticed somtiems, but a cis deletion is associated with an increased risk of severe thalassemia in offspring. i. Cis deletion is when both deletions occurs on the same chromosome, seen in Asians. ii. Trans deletion is when one deletion occurs on each chromosome; seen in africans and some believe that due to the cis deletion that this contributes to high rate of sponataneous abortion.. ii. Trans deletion is when one deletion occurs on each chromosome; seen in Africans, including African Americans. 3. Three genes deleted-severe anemia as the patient is developing in utero there is no clinically detected problem even if 1 alpha is being expressed that is sufficient for the fetus to develop without any clinical problems; when the fetus is born and starts produces ∂2 and ß2, but if there isnt enough ∂2 then the ß w2 will join with another ß2 and thi will form a tetramer that damages RBCs the ß chains form tetramers (HBH) that damage RBCs;HbH is seen on electrophoresis 4. Four genes deleted-lethal in utero (hydrops fetalis);due to no alpha gene and this causes the y chains to form tetramers damage RBCs; Hb Barts is seen on electrophoresis which is a tetramer of gamma chains.