경희대학교 의과대학·의학전문대학원

(1)

철 결핍성 빈혈

경희의대 종양혈액내과 조경삼

(2)

Erythropoiesis

• RBC production • Hemoglobin =

heme + globin

• Heme = a porphyrin ring + an iron atom

(3)

Iron

• Critical element of cell function • Free iron : highly toxic

– Transferrin, ferritin, hemosiderin

• Carry O2 : hemoglobin, myoglobin

• Iron containing enzyme : cytochrome system in mitochodria

• Iron deficiency :

– Decreased Hb synthesis : anemia, hypoxia

(4)

Body iron distribution

Iron content (mg) Male(80 kg) Female(60 kg) Hemoglobin 2,500 1,700 Myoglobin/enzyme 500 300 Transferrin iron 3 3 Iron stores 600 – 1,000 0 - 300

(5)

Iron cycle

• Gain : absorption – diet, medicine

• Loss : the loss of epithelial cells from the skin,

gut, and genitourinary tract blood loss (via

gastrointestinal bleeding, menses, or other forms of bleeding) and

• Male : 1 mg/d ; Female : 1.4 mg/d • RBC : 1 mg/mL

• Daily 0.8 – 1% destruction • Fe turnover : 16 – 20 mg/day

(6)

(7)

Iron absorption

• Proximal small intestine

• Stomach : acidic content

• Gut cell : DMT-1(divalent metal transporter-1) ferritin

---ferroportin (negatively controlled by hepcidin)

• Erythroid hyperplasia : low hepcidin

(8)

Hepcidin

• The central regulator of iron absorption, plasma iron levels, and iron distribution

• Hepatocyte, macrophage, adipocyte

• Inhibit iron flows into plasma from macrophage, duodenal enterocyte, hepatocyte

• Bind to the ferroportin (major entryway for iron into plasma) and causing its degradation

• Hepcidin production is regulated by iron and erythropoietic activity

• hepcidin levels are elevated in a range of

inflammatory disease including rheumatologic

diseases, inflammatory bowel disease, a variety of infections, critical illness, and malignancies

(9)

(10)

Nutritional Iron

• 6 mg/ 1,000 calories • Red meat • M : 6 mg – 15% absorption • F : 11 mg – 12% • Iron deficiency :

– meat-containing diet iron : 20% absorption – Vegetarian diet iron : 5 – 10%

(11)

Food iron absorption

• Compare to ferrous sulfate

• Iron in vegetables : 1/20

• Egg iron : 1/8

• Liver iron : 1/2

(12)

Increased iron

requirement

• Infant

• Children

• Adolescent

• Pregnancy : last trimesters : 5-6mg • Increased erythropoiesis

(13)

Anemia classification

• Etiologic

– Excessive destruction or loss

• Blood loss : acute, chronic

• Hemolysis – Inadequate production • Nutritional • Marrow failure • Others • Morhologic – Macrocytic : • megaloblastic • nonmegaloblastic – Normochromic normocytic – Hypochromic microcytic

(14)

normocytic normochromic

hypochromic microcytic

(15)

Iron deficiency anemia

• One of the most prevalent forms of malnutrition

• Globally 50% of anemia • 841,000 deaths annually

• Africa and part of Asia : 71% • North America : 1.4%

(16)

Stages of iron deficiency

• Negative iron balance : blood

loss(10-20mL/day), pregnancy, rapid growth spurt, inadequate dietay iron

• Iron-deficient erythropoiesis : microcytic cells, hypochromic

reticulocytes

(17)

(18)

Absolute iron deficiency

Dietary (growth/development) Women’s health

Pregnancy/breast feeding Menstrual blood losses Chronic blood loss

Blood donation

Nonsteroidal anti-inflammatory drugs (NSAIDs) Gastrointestinal neoplasms

Gastrointestinal parasites (developing countries) Decreased iron absorption

Celiac disease

Helicobacter pylori infection Autoimmune atrophic gastritis

Functional iron deficiency

(19)

Iron-sequestration syndromes

Anemia of chronic disease/inflammation Autoimmune diseases

Infections Malignancies

Chronic kidney disease Hepcidin-producing adenomas

Iron refractory iron deficiency anemia (IRIDA) Copper deficiency

Molecular defects in iron transport, recycling, and utilization

Divalent metal transporter 1 (DMT1) mutations Hypotransferrinemia

Ferroportin disease Aceruloplasminemia

Hereditary sideroblastic anemias (ALAS2 mutations) Heme oxygenase deficiency

(20)

Clinical presentation of

iron deficiency

• Signs of anemia

– Fatigue – Pallor

– Reduced exercise capacity

• Cheilosis

(21)

Laboratory iron studies

• Serum iron(SI) / Total iron-binding capacity(TIBC) :

50-150/300-360 µg/dL (N) • Serum ferritin : < 15 µg/L

• Bone Marrow iron stores : stainable iron, sideroblast, ringed sideroblast (MDS)

• Red cell protoporhyrin levels : > 100 µg/dL

• Soluble transferrin receptor (sTfR) : 4-9 µg/L (N) • Percent hypochromic red cell (% Hypo)

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(24)

(25)

Differential Diagnosis

Hypochromic microcytic

anemia

– Thalassemia

– Anemia of chronic inflammation – Myelodysplastic syndrome

(26)

(27)

Treatment of

iron-deficiency anemia

• Diet : heme iron • RBC transfusion • Oral iron therapy

• Parenteral iron therapy

– Iron dextran

– Sodium ferric gluconate – Iron sucrose

(28)

Amount of iron needed

Ganzoni’s fomula :

BW(kg) X 2.3 X (15 – pt’s Hb, g/dL) + 500 or 1,000 mg (for stores)

(29)

(30)

Parenteral iron therapy

• Unable to tolerate oral iron

• Absorbtion defect

• Whose need are relatively acute • Epo therapy

• Iron dextran : severe side effect Sodium ferric gluconate

Iron sucrose

(31)

Iron prep. ( 본원 )

• Ferrous sulfate

– Feroba-You : 256 mg (80 mg) / tab

• Iron acetyl-transferrin hydroglycerin – Bolgre Soln : 2 mL (40 mg) / 15 mL

• Iron protein succinylate

– Hemo-Q : 800 mg (40 mg) / 15 mL • Ferric chloride

(32)

1st Case 25 세 , 여자 ; 주소 : 창백한 피부 • P.I. : 서서히 시작된 운동시 호흡곤란 , 불규칙한 월경 , 채식 위 주로 식사 • CBC : RBC : 3,200,000/uL, Hb : 7.4 g/dL, Hct : 23% MCV : 72 fL(81-99), MCH : 23.1pg/cell(27-31), MCHC : 32.1 g/dL(33-37) WBC : 8,500/uL, Platelet : 485,000/uL

• Peripheral blood smear : Hypochromic, microcytic, anisocytosis (++), pikilocytosis (+)

• Chemistry : serum Fe : 26 ug/dL, TIBC : 460 ug/dL Ferritin : 15 ng/mL

(33)

Normocytic normochromic

Hypochromic microcytic

(34)

진단

• Hypochromic, microcytic anemia

– Fe deficience – Inflammation – Thalassemia – Sideroblastic • Fe deficiency anemia – Causes

(35)

• 2nd Case : 40 세 , 여자 ; 주소 : 운동시 호흡곤란 P.I. : 서서히 진행 , 창백한 피부 , 잘 부러지는 손톱 , 규칙적이나 양이 많은 월경 • 3rd Case : 58 세 , 여자 ; 주소 : 창백한 피부 P.I. : 서서히 진행되는 운동시 호흡곤란 , 채식위주로 식사 PMH : 5 년전 위암으로 위절제술 , 7 년전 폐 경 • 4th Case : 50 세 , 남자 ; 주소 : 운동시 호흡곤란 P.I. : 서서히 진행 , 식사는 규칙적이고 균형 잡힘 , 특별한 약물 복용 없음 •

(36)

(37)

진단

• 1st case : blood loss (mense), diet (+),

demend (?)

• 2nd case: blood loss (mense), diet (?),

demend (-): gynecological problem

• 3rd case : blood loss (-), diet (+),

demend (-) : absorption (gastrectomy)

• 4th case : blood loss (?), diet (-),

(38)

Treatments of Cases

• 1st Case :

• 2nd Case :

• 3rd Case :

(39)

만성 질환 빈혈

경희의대 종양혈액내과 조경삼

(40)

만성 질환에 수반된 빈혈

(Anemia of Chronic Disorders,ACD)

• 철결핍 빈혈 다음으로 가장 흔한 빈혈이다 . • 기저질환이 호전되어야 빈혈도 호전된다 . • 임상적으로 빈혈의 증상에 기저질환의 다양한 증 상들이 겹쳐서 나타난다 . • 빈혈의 심한 정도는 대개 기저질환의 정도와 비례한다 . • 만성질환 외의 빈혈을 악화시키는 요인이 있 는지 확인이 필요하다 .

(41)

Iron-sequestration syndromes

Anemia of chronic disease/inflammation Autoimmune diseases

Infections Malignancies

Chronic kidney disease Hepcidin-producing adenomas

Iron refractory iron deficiency anemia (IRIDA) Copper deficiency

Molecular defects in iron transport, recycling, and utilization

Divalent metal transporter 1 (DMT1) mutations Hypotransferrinemia

Ferroportin disease Aceruloplasminemia

Hereditary sideroblastic anemias (ALAS2 mutations) Heme oxygenase deficiency

(42)

Anemia of Chronic

Disorders

• Anemia of Chronic Inflammation • Anemia of Uremia

• Anemia due to Endocrine Failure • Anemia of Liver Disease

(43)

Anemia of Chronic Inflammation

• (1) 감염 : 세균심내막염 , 골수염 , 폐농양 , 결핵 , 신우신 염 ( 급성염증 시 1-2 일에 혈색소 2-3g/dL 감소 가능 , 용혈도 관여 ) • (2) 교원성 질환 : 류마티스관절염 ,SLE, 혈관염 (temporalarteritis), sarcoidosis,

regional enteritis, tissue injury

• (3) 종양 :HodgkinDisease, 폐암 , 유방암 , 등

( 철결핍 , 골수침윤 , 엽산결핍 , 용혈빈혈 , 약제 , 방사선요법 등에 의한 빈혈 감별 필요 )

(44)

임상소견 ( 혈액 소견

)

• 대개 증상 없음 . • 노령에는 증상 나타날 수 있음 .( 심혈관증상 ) • Reti. index 2.0 이하 . • 질환의 기간과 중증도에 비례 • (1) 경도 또는 중등도 ( 혈색소치 9-11g/dL), normocytic or slightly microcytic

• (2) 골수소견 : 정상 적혈구 성숙 , 철아구 감소 , 대 식구 내 철 증가

• (3)Reti. 감소 , 혈청철 감소 , transferrin 치 감소 , transferrin saturation : 15-20%, ferritin 은 증가 또는 정상

(45)