Lecturer Prof. Yu.R. Kovalev

8/14/2019 Lecturer Prof. Yu.R. Kovalev

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ANEMIAS

Lecturer prof. Yu.R. Kovalev


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DEFINITION AND CLASSIFICATION

Anemia is defined as a reduction of hemoglobin(hematocrit) levels below the normal values for thedifferent age and sex groups. Hemoglobin is less than13.5 g/dL (hematocrit < 41%) in males or less than 12g/dL (hematocrit < 37%) in females.

1. Microcytic2. Normocytic3. Macrocytic

1. Hypochromic2. Normochromic3. Hyperchromic

CLASSIFICATION BASED ON ERYTHROCYTEMORPHOLOGY


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COMMON CAUSES

1. Nutritional anemia due to deficiency of essential nutrients or this absorptiondisturbances such as iron, proteins, folates, vit Cand B12

2. Hemorrhagic anemia due to excessivemenstrual blood losses, hemorroids,gastrointestinal carcinoma, bleeding peptic ulcer,parasites or other causes lead to iron deficiency.

3. Hemolytic anemia4. Hypoplastic anemia5. Myelophtisic anemia


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IRON DEFICIENCY

Iron deficiency is the most common cause of anemiaworldwide. Total body iron ranges between 2 g and 4g: approximately 50 mg/kg in men and 35 mg/kg inwomen. Most (70-95%) of iron is present inhemoglobin in circulating red blood cells. Asidefrom circulating red blood cells, the major locationof iron in the body is the storage pool, as ferritin or as hemosiderin and in macrophages. The range for storage iron is wide (0.5 g); approximately 25% of women have none.


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IRON DEFICIENCY

The average diet contains 10-15 mg of iron per day.About 10% of this amount is absorbed. Absorptionoccurs in the stomach, duodenum, and upper

jejunum. Dietary iron present as heme is efficientlyabsorbed (10-20%) but nonheme iron less so (1-5%),largely because of interference by phosphates,tannins, and other food constituents. Small amountsof iron approximately 1 mg/d are normally lostthough exfoliation of skin and mucosal cells. Thereis no physiologic mechanism for increasing normalbody iron losses. In general, iron metabolism isbalanced between absorption of 1 mg/d and loss of 1mg/d.


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IRON DEFICIENCY

Pregnancy may also upset the iron balance, sincerequirements increase to 2-5 mg of iron per dayduring pregnancy and lactation.Decreased iron absorption can on very rare

occasions cause iron deficiency and usually occursafter gastric surgery, though concomitant bleedingis frequent.


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CLINICAL FEATURES Symptoms of iron deficiency anemia are those of theanemia itself (easy fatigability, tachycardia,palpitations and tachypnea on exertion). Severedeficiency causes skin and mucosal changes,

including a smooth tongue, brittle nails, andcheilosis. Dysphagia because of the formation of esophageal webs (Plummer-Vinson syndrome) alsooccurs. Many iron-deficient patients develop pica,

craving for specific foods.


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CLINICAL FEATURES

Stomatitis angularisPica chlorotica: thepatient eats Inediblesubstances as earth,clay, lime

(geophagia), soap,chalk, plaster a.o.Pallor with greenish shade.


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CLINICAL FEATURES

Brittle spoon-shaped nails(koilonychia).

esophageal webssideropenic disphagia

(Plummer-Vinsons syndrom)


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LABORATORY INDICES

MCH: mean corpuscular hemoglobin

hemoglobin

MCH = ------------------------------- (pg or 10 -12 g)RBC count

Normal values: 24 34 pg< 24 hypochromia; > 34 hyperchromia


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LABORATORY INDICES

NORMAL VALUESIron 9 31 micromol/lIron-binding capacity 45 80 micromol/l

Ferritin male: 16 300 ng/lfemale: 4 160 ng/l

Transferrin 1,9 3,75 g/l


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LABORATORY FINDINGS

In the early stages, the MCV and MCH remainnormal. Subsequently, they fall and the blood smear shows hypochromic microcytic cells. With further progression, anisocytosis (variations in red blood

cell size) and poikilocytosis (variation in shape of red cells) develop.The platelet count is commonly increased.Bone marrow shows nonrmoblaslic hyperplasia withabsence of stainable iron. It is not necessary to dobone marrow examination in all cases of irondeficiency anaemia.


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LABORATORY FINDINGS

NormalHypochromicmicrocytic cells


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LABORATORY FINDINGS

Iron deficiency: the serum ferritin will becomeabnormally low. A ferritin value less than 30 g/L isa highly reliable indicator of iron deficiency. Theserum total iron-binding capacity (TIBC) rises.

Serum iron values decline.


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MANAGMENT

The better treatment is ferrous sulfate, 325 mgthree times daily, which provides 180 mg of iron daily of which up to 10 mg is absorbed.

An appropriate response is a return of thehematocrit level halfway toward normal within3 weeks with full return to baseline after 2months. Reticulocytosis will increase within

5-7 days.


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MANAGMENT

Iron therapy should continue for 3-6 monthsafter restoration of normal hematologicvalues in order to replenish iron stores.Because of the possibility of complications(anaphylactic reactions, hemosiderosis) parenteraliron therapy should be used only in cases of persistent anemia after a reasonable course of oraltherapy. But newer iron complexes have lower rateof adverse effects (iron gluconat).

VITAMIN B12 DEFICIENCY


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All vitamin B12 comes from the diet and is present inall foods of animal origin. The daily absorption of vitamin B12 is 5 mg.After being ingested, vitamin B12 is bound tointrinsic factor, a protein secreted by gastric parietalcells. The vitamin B12-intrinsic factor complextravels through the intestine and is absorbed in theterminal ileum by cells with specific receptors for thecomplex. It is then transported through plasma bytransport proteins and stored in the liver. The liver contains 2-5 mg of stored vitamin B12 . So vitaminB12 deficiency develops more than 3 years after vitamin B12 absorbtion ceases.


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Vitamin B12 belongs to the family of cobalamins andserves as a cofactor for two important reactions inhumans. As methylcobalamin, it is a cofactor for methionine synthetase in the conversion of homocysteine to methionine and asadenosylcobalamin for the conversion of methylmalonyl-CoA to succinyl-CoA.


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The disturb of the first reaction leads to defect in DNA

synthesis (megaloblastic anemia, affection of mucosae)and high level of plasma homocysteine (risk factor for thrombosis). There are also deficiency of cholin andphospholipids (nervous system damage).If the second reaction impaired the metabolism of fattyacids changes and toxic methylmalonyl and propionylCoA accumulate (neurologic complications).


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CAUSES OF VITAMIN B12 DEFICIENCY Dietary deficiency (rare) Decreased production of intrinsic factor Pernicious anemia

Gastrectomy Competition for vitamin B12 in gut

Blind loop syndromeFish tapeworm (Diphyllobothrium latum)

Pancreatic insufficiency Decreased ileal absorbtion of vitamin B12

Resection of the ileumCrohns disease

Strict vegetarians Transcobalamin II deficiency (rare)


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PERNICIOUS ANEMIA

PA is the most common cause of cobalaminedeficiency from either atrophy of the gastricmucosae or autoimmune destruction of parietal cells.

There are antiparietal cells antibodies directedageinst H, K-ATPase and anti-IF antibodies.The incindence of PA is increased in patientswith some deseases is thought of immuneorigin: Graves deseae, myxedema, thyroiditis,adrenocortical insufficiency a.o.


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CLINICAL FEATURES

PA is the desease of the elderly and rare under 30.B 12 deficiency produces changes in mucosal cells,leading to glossitis, as well as other gastrointestinaldisturbances, such as anorexia and diarrhea. The

spleen is palpable in 20% of patients.Neurologic syndrome. The posterior columnsimpaired (demyelination): paresthesias , difficultywith balance, decreased vibration sense, neurogenicbladder. May be dementia and other neuropsychiatric changes.

CLINICAL FEATURES


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CLINICAL FEATURES Patients are usually paleand may be mildly icteric,

because of anemia andhemolysis of hemoglobin-containing megaloblasts inbone marrow.

Hunters glossitis; thenpapillae are atrophied andtongue becomes smoothand glazed.

CLINICAL FEATURES


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CLINICAL FEATURES

Posterior columnsimpairing


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LABORATORY FINDINGS

The hallmark of vitamin B 12 deficiency ismegaloblastic anemia. The anemia may be severe,with hematocrits as low as 10-15%, and hemoglobine2,0 4,0 g/dl. The MCV is usually strikingly elevated,

between 110 and 140 fL. There are anisocytosis andpoikilocytosis, nuclear material in erythrocytes:Howel-Jolly bodies and Cabot's rings.


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LABORATORY FINDINGS

A characteristic finding is the macroovalocyte. Theneutrophils are hypersegmented. Typical featuresinclude a mean lobe count greater than four or thefinding of six-lobed neutrophils. The reticulocyte

count is reduced. Because vitamin B 12 deficiencyaffects all hematopoietic cell lines, in severe casesthe white blood cell count and the platelet count arereduced, and pancytopenia is present.


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LABORATORY FINDINGS

normal


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LABORATORY FINDINGS

Bone marrow morphology is characteristicallyabnormal. Megaloblastic changes (abnormally largecell size and asynchronous maturation of thenucleus and cytoplasm) is present. The marrow

cellularity is often increased, but production of redblood cells is increased (ineffective erythropoesis).The diagnosis of vitamin B 12 deficiency is made byfinding an abnormally low vitamin B 12 serum level.

Whereas the normal vitamin B 12 level is 150-350pg/mL, most patients with overt vitamin B 12 deficiency will have serum levels less than 100pg/mL.


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MANAGMENT

Patients with pernicious anemia are often treatedwith parenteral therapy. Intramuscular injections of 200 400 g of vitamin B 12 are adequate for eachdose. Replacement is usually given daily for the first

week, weekly for the first month, and then 100 gmonthly for life.Patients respond to therapy with an immediateimprovement in their sense of well-being. A brisk

reticulocytosis occurs in 5-7 days, and thehematologic picture normalizes in 2 months.

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Lecturer Prof. Yu.R. Kovalev