¼±Åà - È­»ìǥŰ/¿£ÅÍŰ ´Ý±â - ESC

 

Chap 107. Megaloblastic anemias

Megaloblastic anemia´Â DNAÇÕ¼º Àå¾Ö·Î ¹ß»ýÇÑ´Ù. ´Ù¼Ò ºü¸¥ turnover¸¦ °¡Áö´Â ¼¼Æ÷,

ƯÈ÷ hematopoietic precursors & GI epithelial cells¿¡¼­ 1Â÷ÀûÀ¸·Î ¹ß»ýÇÑ´Ù.

¼¼Æ÷ºÐ¿­Àº ´À¸®Áö¸¸, ¼¼Æ÷ÁúÀº Á¤»óÀûÀ¸·Î ¹ß´ÞÇϹǷÎ, megaloblastic cellsÀº Ä¿Áö°Ô µÇ°í

RNA:DNAºñ´Â Áõ°¡ÇÏ°Ô µÈ´Ù. megaloblastic erythroid progenitors´Â °ñ¼ö¿¡¼­ ÆÄ±«µÈ´Ù.

±×·¯¹Ç·Î marrow cellularity´Â Áõ°¡µÇÁö¸¸ ÀûÇ÷±¸ »ý»êÀº °¨¼ÒÇϴµ¥ À̸¦ "ineffective

erythropoiesis"¶ó ÇÑ´Ù.

´ëºÎºÐÀÇ megaloblastic anemia´Â cobalamin(vitB12) and/or folic acid°áÇÌÀ¸·Î ¹ß»ýÇÑ´Ù.

megaloblastic anemia¿Í °ü·ÃµÈ ¿©·¯ °¡Áö ÀÓ»ó»óȲÀÌ Tab 107-1¿¡ ³ª¿­µÇ¾î ÀÖ´Ù.

I. Physiologic & Biochemical considerations

1. Folic acid

folic acid´Â ¸¹Àº ½Ä¹°°ú ¼¼±Õ¿¡ ÀÇÇØ ÇÕ¼ºµÇ´Âµ¥ °úÀϰú ä¼Ò°¡ ÀÏÂ÷ÀûÀÎ °ø±Þ¿øÀÌ´Ù.

ÀÏÀÏ ÃÖ¼Ò ¿ä±¸·®Àº ¾à 50 ugÀÌÁö¸¸ ÀӽŰú °°ÀÌ ¿ä±¸·®ÀÌ Áõ°¡ÇÒ¶§´Â ¸î¹è ´õ ÇÊ¿äÇÏ´Ù.

Á¤»óÀÎÀÇ folic acid ÀúÀå·®Àº 5-20 mgÀÌ¸ç ±×Áß ¹ÝÀº liver¿¡ ÀúÀåµÈ´Ù.

* Fig 107-1 folate metabolism

folate´Â purine, dTMP, methionineÇÕ¼º¿¡ ÇʼöÀûÀÌ´Ù.

folate compoundÀÇ ÁÖ±â´ÉÀº 1-carbon moieties(methyl & formyl groups)¸¦ ¿©·¯ °¡Áö

organic compounds·Î À̵¿½ÃŰ´Â °ÍÀÌ´Ù. ÀÌ·¯ÇÑ 1-carbon moietiesÀÇ source´Â ÈçÈ÷

serineÀε¥ ÀÌ´Â THF¿Í ¹ÝÀÀÇÏ¿© glycine°ú N5,10-methyleneTHF¸¦ »ý»êÇÑ´Ù.

DHF reductase¸¦ ¾ïÁ¦ÇÏ´Â ¸¹Àº ¾àÀÌ folate deficiency¸¦ ÃÊ·¡ÇÑ´Ù.

2. Cobalamin

À¯ÀÏÇÑ À½½Ä °ø±Þ¿øÀº °í±â ȤÀº ³«³ó½ÄǰÀÌ´Ù. ÀÏÀÏ Ãּҿ䱸·®Àº 2.5 ugÀÌ´Ù.

À§³» ¼ÒÈ­Áß À½½Ä³» cobalaminÀº À¯¸®µÇ°í gastric R binder¿Í stable complex¸¦ Çü¼ºÇÑ´Ù.

½ÊÀÌÁöÀåÀ¸·Î µé¾î°¡¸é cobalamin-R binder complex´Â ºÐÇØµÇ¾î cobalaminÀº À¯¸®µÇ¾î IF

¿Í °áÇÕÇÑ´Ù.

cobalamin-IF complex´Â ´Ü¹éºÐÇØ¿¡ ÀúÇ×Çϸ鼭 distal ileum±îÁö À̵¿ÇÏ¿© mucosal brush

border¿¡ ÀÖ´Â specific receptor¿¡ °áÇÕÇÑ´Ù. IFµµ cell-directed carrier proteinÀ¸·Î ÀÛ¿ëÇÑ´Ù.

receptor-bound cobalamin-IF complex´Â ileal mucosal cell¿¡ °áÇÕÇÏ¿© IF´Â ÆÄ±«µÇ°í

cobalaminÀº ´Ù¸¥ transport protein(transcobalamin II)À¸·Î ÀüÇØÁø´Ù. cobalamin-TC II

complex´Â Ç÷¾×³»·Î À̵¿ÇÏ¿© °£, °ñ¼ö ¹× ´Ù¸¥ ¼¼Æ÷·Î µé¾î°£´Ù(Fig 107-2).

Á¤»óÀûÀ¸·Î ¾à 2mgÀÇ cobalaminÀº °£¿¡, ´Ù¸¥ 2mgÀº ¸ö ¿©·¯°÷¿¡ ÀúÀåµÈ´Ù. ÀÏÀÏ ÃÖ¼Ò ¿ä±¸

·®¿¡¼­ º¸¸é, Èí¼ö°¡ °©ÀÚ±â ÁߴܵǾúÀ» ¶§ cobalamin°áÇÌÀÌ ³ªÅ¸³ª±â±îÁö´Â 3-6³âÀÇ ½Ã°£

ÀÌ ÇÊ¿äÇÏ´Ù. ºñ·Ï TC II´Â »õ·ÎÀÌ Èí¼öµÇ´Â cobalaminÀÇ acceptorÀÌÁö¸¸ ´ëºÎºÐÀÇ Ç÷¾×³»

cobalaminÀº TC I(gastric R binder¿Í ¹ÐÁ¢ÇÑ °ü·ÃÀÌ ÀÖ´Â glycoprotein)¿¡ °áÇյǾî ÀÖ´Ù.

TC IÀº ºÎºÐÀûÀ¸·Î ¹éÇ÷±¸·ÎºÎÅÍ ³ª¿Â´Ù. ¸ð¼øµÈ Á¡Àº ´ëºÎºÐ Ç÷¾×³» cobalaminÀº Àå³»¿¡¼­

Èí¼öµÇ´Â ¸ðµç cobalaminÀ» TC II°¡ ¿î¹ÝÇÒÁö¶óµµ TC IIº¸´Ù TC I¿¡ ´õ ¸¹ÀÌ °áÇյǾî Àִµ¥

ÀÌ´Â TC II¿¡ °áÇÕµÈ cobalaminÀÌ Ç÷Áß¿¡¼­ »¡¸® Á¦°ÅµÇ±â ¶§¹®À¸·Î ¼³¸íÇÒ¼ö ÀÖ´Ù(t1/2 =

1h). ¹Ý¸é, TC I¿¡ °áÇÕµÈ cobalaminÀÇ Á¦°Å´Â ¿©·¯³¯ÀÌ ÇÊ¿äÇÏ´Ù. TC IÀÇ ±â´ÉÀº ¾Ë·ÁÁ®ÀÖÁö

¾Ê´Ù.

cobalaminÀº Àΰ£¼¼Æ÷¿¡¼­ µÎ°¡Áö È¿¼Ò¿¡ ´ëÇÑ ÇʼöÀû cofactorÀÌ´Ù. Ä¡·áÀûÀ¸·Î ÀÌ¿ëÇÏ´Â

Á¦Á¦´Â cyanocobalamin(=vit B12)ÀÌ´Ù. À̰ÍÀÇ »ý¸®Àû ¿ªÇÒÀº ¾Ë·ÁÁ® ÀÖÁö ¾ÊÀ¸¸ç Á¶Á÷¿¡¼­

»ç¿ëµÇ±â Àü¿¡ »ý¹°ÇÐÀû Ȱ¼ºÇüÀ¸·Î ÀüȯµÈ´Ù.

methylcobalaminÀº methionine synthase(homocysteine -> methionine)¸¦ À§ÇØ ÇÊ¿äÇÑ Çü

ÅÂÀÌ´Ù. ÀÌ °úÁ¤ÀÌ ¼Õ»óµÇ¸é, folate metabolismÀÌ È寮·¯Áø´Ù. methotrexateÄ¡·á ¿Ü¿¡

cobalamin & folate deficiency¶§ÀÇ megaloblastic change´Â dTMP»ý»êºÎÁ·°ú °ü·ÃÀÖ´Ù.

plasma homocysteine levelsÀº µÑ´Ù¿¡¼­ »ó½ÂÇÑ´Ù. °í³óµµÀÇ plasma homocysteineÀº µ¿,

Á¤¸Æ Ç÷ÀüÁõÀÇ À§ÇèÀÎÀÚÀÌ´Ù. ±×·¯³ª folate or cobalamin deficiency¿¡ ÀÇÇÑ

hyperhomocysteinemia°¡ thrombosisÀÇ ¿øÀÎÀÎÁö ȤÀº Ä¡·á¿¡ ´ëÇÑ ¹ÝÀÀÀ» º¯È­½ÃŰ´ÂÁö¿¡

´ëÇØ¼­´Â ¾Ë·ÁÁ® ÀÖÁö ¾Ê´Ù.

homocysteine -> methionineÀ¸·ÎÀÇ ÀüȯÀå¾Ö´Â ºÎºÐÀûÀ¸·Î´Â cobalamine deficiency¿¡ ÀÇ

ÇÑ ½Å°æÇÐÀû ÇÕº´ÁõÀÇ ¿øÀÎÀÌ´Ù. ÀÌ·¯ÇÑ ¹ÝÀÀ¿¡¼­ Çü¼ºµÈ methionineÀº choline &

choline-containing phospholipidsÀÇ »ý»êÀ» À§ÇØ ÇÊ¿äÇÏ´Ù. ½Å°æ°è ¼Õ»óÀº Àû¾îµµ ºÎºÐÀûÀ¸

·Î´Â methionine»ý»êÀÌ °¨¼ÒÇϱ⠶§¹®ÀÌ´Ù.

II. Clinical disorders

1. ºÐ·ù(Tab 107-1)

2. Cobalamin deficiency

cobalamin deficiencyÀÇ ÀÓ»óÀû Ư¡Àº Ç÷¾×, À§Àå°ú ½Å°æ°è¸¦ ħ¹üÇÑ´Ù.

¨ç hematologic manifestations

¸Å¿ì µå¹°°Ô´Â thrombocytopenia¿¡ ÀÇÇÑ purpura°¡ ³ªÅ¸³¯¼öµµ ÀÖÀ¸³ª °ÅÀÇ ÀüÀûÀ¸·Î

ºóÇ÷ÀÌ´Ù.

ºóÇ÷ÀÇ Áõ»óÀ¸·Î weakness, light-headedness, vertigo, tinnitus, palpitation, angina,

congestive failure Áõ»óÀÌ ³ªÅ¸³¯ ¼ö ÀÖ´Ù. ÁøÂû»ó ȯÀڴ â¹éÇÏ°í ¾à°£ ³ë¶õ ÇÇºÎ¿Í ´«À»

º¸ÀδÙ. bilirubin levelÀÌ Áõ°¡ÇÑ °ÍÀº °ñ¼ö¿¡¼­ erythroid cell turnover°¡ ºü¸£±â ¶§¹®ÀÌ´Ù.

¸Æ¹ÚÀº ºü¸£°í ½ÉÀåÀº ºñ´ëÇØÁö¸ç, ûÁøÇϸé systolic flow murmur¸¦ µéÀ»¼ö ÀÖ´Ù.

¨è GI manifestations

sore tongueÀ» È£¼ÒÇϰí, smooth & beefy red color¸¦ º¸ÀδÙ. anorexia with moderate wt

loss°¡ Àú¸íÇØÁö°í ¼³»ç ȤÀº ´Ù¸¥ À§Àå°ü Áõ»óÀÌ µ¿¹ÝµÈ´Ù.

¨é neurologic manifestations

½Å°æÇÐÀû Áõ»óÀº ÈçÈ÷ Ä¡·á¸¦ ÇØµµ ¿ÏÀüÈ÷ ȸº¹µÇÁö ¾Ê´Â´Ù. º´¸®ÀûÀ¸·Î demyelinationÀ¸·Î

½ÃÀÛÇÏ¿© axonal degeneration, °á±¹¿£ neuronal death¸¦ ÃÊ·¡ÇÑ´Ù. ÀÌ´Â ºñ°¡¿ªÀûÀÌ´Ù.

ħ¹üµÇ´Â °÷Àº peripheral nerves, spinal cordÀÇ post & lat. columns, cerebrum. Áõ»ó ¹×

¡Èķδ numbness, paresthesia in the extremities(earlist neurologic sx), weakness,

ataxia, sphincter disturbance°¡ »ý±æ¼ö ÀÖ´Ù. reflex´Â °¨¼ÒÇϰųª Áõ°¡Çϸç Romberg &

Babinski sign¾ç¼ºÀÌ´Ù. position & vibration sense´Â °¨¼ÒÇϸç mental disturbance°¡

»ý±æ¼öµµ Àִµ¥ mild irritability & forgetfulness(°Ç¸ÁÁõ)¿¡¼­ºÎÅÍ severe dementia or frank

psychosis±îÁö ´Ù¾çÇÏ´Ù. neurologic disease´Â Á¤»ó Hct & Á¤»ó RBC index¸¦ °¡Áø ȯÀÚ

¿¡¼­µµ ¹ß»ýÇÒ¼ö ÀÖÀ½À» ¸í½ÉÇØ¾ß ÇÑ´Ù.

folate°ø±ÞÀº ¸¹Àº µµ¿òÀÌ µÇÁö¸¸, cobalamin deficiency¶§´Â ½Å°æÇÐÀû ¹ßÇöÀ» Áõ°¡½Ãų ¼ö

ÀÖ´Ù.

1) À½½Ä¿¡¼­ÀÇ cobalamin À¯¸®Àå¾Ö

À½½Ä³» cobalaminÀº °í±â³» È¿¼Ò¿Í °­ÇÏ°Ô °áÇյǸç À§³» HCl°ú pepsin¿¡ ÀÇÇØ È¿¼Ò¿Í ºÐ¸®

µÈ´Ù.

70¼¼ ÀÌ»ó ³ëÀÎÀº À½½Ä¿¡¼­ cobalaminÀ¯¸®°¡ ÈçÈ÷ µÇÁö ¾ÊÁö¸¸ crystalline B12(multivitamin

¿¡¼­ °¡Àå ÈçÈ÷ ¹ß°ßµÇ´Â ÇüÅÂ)¸¦ Èí¼öÇÒ ´É·ÂÀº °¡Áö°í ÀÖ´Ù. cobalamin release defectÀÇ

Á¤È®ÇÑ ¹ß»ýÀº ¾Ë±â ¾î·ÆÁö¸¸ 70¼¼ À̻󿡼­ ´ë·« 10¡­>50%ÀÌ´Ù. À§»ê »ý¼ºÀ» ¾ïÁ¦ÇÏ´Â

¾à(¿¹: omeprazole)Àº À½½Ä¿¡¼­ cobalaminÀ¯¸®¸¦ ¹æÇØÇÑ´Ù.

2) pernicious anemia

cobalamin deficiencyÀÇ °¡Àå ÈçÇÑ ¿øÀÎÀ̸ç IFÀÇ °áÇÌÀ¸·Î ¹ß»ýÇÑ´Ù. IF °áÇÌÀº gastric

mucosa atrophy³ª parietal cellÀÇ autoimmune destruction¿¡ ÀÇÇÑ´Ù. ºÏÀ¯·´°ú ¾ÆÇÁ¸®Ä«°è

¹Ì±¹Àο¡¼­ °¡Àå ÈçÈ÷ ¹ß°ßµÇ°í ³²À¯·´°ú ¾Æ½Ã¾Æ¿¡¼­´Â ´ú ÈçÇÏ´Ù. ³²³àºñ´Â µ¿ÀÏÇÏ¸ç Æò±Õ

60¼¼¿¡ ¹ß»ýÇÏ°í ºñ·Ï typical RA°¡ 10¼¼ ¹Ì¸¸¿¡¼­ º¼¼ö ÀÖÁö¸¸ 30¼¼ ¹Ì¸¸Àº µå¹°´Ù.

Graves' disease, myxedema, thyroiditis, idiopathic adrenocortical insufficiency, vitiligo,

hypoparathyroidism°ú °°Àº ¸é¿ªÁúȯ¿¡¼­ ºóµµ°¡ Áõ°¡ÇÑ´Ù. ¶ÇÇÑ È¯ÀÚÀÇ 90%¿¡¼­

antiparietal cell Ab¾ç¼ºÀ̰í, 60%¿¡¼­ anti-IF Ab¸¦ °¡Áö°í ÀÌ´Ù.

antiparietal cell Ab´Â gastric atrophy without pernicious anemiaȯÀÚÀÇ 50%¿¡¼­ ¹ß°ßµÇ°í

unselected ptÀÇ 10-15%¿¡¼­µµ ¹ß°ßµÈ´Ù. ±×·¯³ª ÀÌ·± °æ¿ì¿¡¼­µµ anti-IF Ab´Â ¾ø´Ù.

ȯÀÚÀÇ Ä£Ã´¿¡¼­ ºóµµ°¡ Áõ°¡ÇÑ´Ù. parietal cellÀÇ ÆÄ±«´Â cytotoxic T cell¿¡ ÀÇÇØ ¸Å°³µÇ´Â

°ÍÀ¸·Î »ý°¢µÈ´Ù.

agammaglobulinemiaȯÀÚ¿¡¼­ ¸Å¿ì ÈçÇѵ¥ ÀÌ´Â º´Àο¡¼­ cellular immune systemÀÌ ÁÖ¿ª

ÇÒÀ» ÇÔÀ» ÀǹÌÇÑ´Ù. ¹Ý´ë·Î H. pylori´Â pernicious anemia¿¡¼­ parietal cell destructionÀ»

ÀÏÀ¸Å°Áö ¾Ê´Â´Ù.

ÀÓ»ó¹ßÇöÀº ÀÏÂ÷ÀûÀ¸·Î cobalamin deficiency¿Í °°´Ù. labÀº hypergastrinemia &

pentagastrin-fast achlorhydria¸¦ º¸ÀδÙ.

ÀûÀýÇÑ replacement tx¸¦ ÅëÇÏ¿© ȯÀÚ´Â cobalamin deficiency·Î ÀÎÇÑ ¸ðµç ÀÌ»óÀÌ ¿ÏÀüÈ÷

±³Á¤µÈ´Ù(½Å°æ°èÀÇ ºñ°¡¿ªÀû º¯È­¸¦ Á¦¿ÜÇϰí´Â).

3) postgastrectomy

total gastrectomy or gastric mucosaÀÇ extensive damageÈÄ IF source°¡ ¾ø¾îÁö¹Ç·Î

megaloblastic anemia°¡ ¹ß»ýÇÑ´Ù. ±×·± ȯÀÚ¿¡¼­ °æ±¸·Î Åõ¿©ÇÑ cobalaminÀÇ Èí¼ö´Â ¼Õ»ó

µÈ´Ù. megaloblastic anemia´Â partial gastrectomyÈÄ¿¡µµ »ý±æ¼ö ÀÖÀ¸³ª ºóµµ´Â total

gastrectomyº¸´Ù ³·´Ù.

partial gastrectomyÈÄ cobalamin deficiency¿øÀÎÀº ºÐ¸íÇÏÁö ¾ÊÁö¸¸ À½½ÄÀ¸·ÎºÎÅÍ

cobalamin À¯¸®Àå¾Ö, Àå³»¼¼±ÕÁõ½ÄÀÌ Á¦½ÃµÇÁö¸¸ Ç×»ýÁ¦¿¡ ´ëÇÑ ¹ÝÀÀÀº ÈçÄ¡ ¾Ê´Ù.

4) intestinal organisms

stricture, diverticulum, anastomosis, "blind loops"¿Í °°Àº ÇØºÎÇÐÀû º´º¯ ȤÀº DM,

scleroderma, amyloid°°Àº pseudoobstruction¿¡ ÀÇÇØ Á¤Ã¼°¡ »ý±â¸é megaloblastic anemia

°¡ »ý±æ¼ö ÀÖ´Ù. ÀÌ·± ºóÇ÷Àº ¼ÒÀå³» ¼¼±ÕÀÇ Áõ½Ä¿¡ ÀÇÇÏ¸ç ¼¼±ÕÀÌ Èí¼öÀüÀÇ cobalaminÀ»

¼ÒºñÇϱ⠶§¹®ÀÌ´Ù.

5) ileal abnormalities

tropical sprue¿¡¼­ cobalamin deficiency°¡ ÈçÇѵ¥ nontropical sprue¿¡¼± µå¹® ÇÕº´ÁõÀÌ´Ù.

distal ileumÀÇ Èí¼ö´É¿¡ ¼Õ»óÀÌ °¡´Â °æ¿ì¿¡ cobalamin deficiency°¡ »ý±ä´Ù. ƯÁ¤ÁúȯÀ¸·Î

´Â regional enteritis, Whipple's disease, tuberculosis°¡ ÀÖ´Ù. ileal resectionÈÄ¿¡

cobalamin malabsorptionÀ» º¼¼ö ÀÖ´Ù. ZES¶§µµ cobalamin malabsorptionÀ» ÀÏÀ¸Å³¼ö ÀÖ´Â

µ¥ ¼ÒÀåÀ» »ê¼ºÈ­½ÃÅ´À¸·Î½á IF¿¡ ´ëÇÑ R binderÀÇ À̵¿À» ´À¸®°Ô ÇÔÀ¸·Î½á cobalamin-IF

complex¿Í ileal receptor¿ÍÀÇ °áÇÕÀ» ¹æÇØÇÑ´Ù.

6) Nitric oxide

¸¶ÃëÁ¦·Î NO¸¦ ÈíÀÔÇϸé endogenous cobalaminÀ» ÆÄ±«ÇÑ´Ù.

3. Folic acid deficiency

1) inadequate intake

alcoholics: ¼·ÃëºÎÁ·, folate metabolismÀå¾Ö

narcotic addicts: malnutrition

2) ¿ä±¸·® Áõ°¡

chronic hemolytic anemia, very active erythropoiesis, pregnant woman, chronic

hemodialysis

3) malabsorption: tropical sprue

4. Drugs

1) direct inhibitors of DNA synthesis

purine analogues: 6-TG, azathioprine, 6-MP

pyrimidine analogues: 5-FU, cytosine arabinoside

±âŸ: hydorxyurea, procarbazine

antiviral agent: zidovudine

2) folate antagonists

MTX: DHF reductaseÀÇ powerful inhibitor

±× ¿Ü DHF reductase inhibitor: pentamidine, trimethoprim, triamterene, pyrimethamine

3) ±âŸ: anticonvulsants(phenytoin, pyrimedone, phenobarbital)

5. ±âŸ

1) hereditary: hereditary orotic aciduria, Lesch-Nyhan syndrome

2) refractory megaloblastic anemia: myelodysplasiaÀÇ ÇÑ ÇüÅÂ

6. Megaloblastic disease without anemia

1) Acute megaloblastic anemia

ÈçÈ÷ NO anesthesiaÈÄ¿¡ º¸ÀÌÁö¸¸ ÁýÁßÄ¡·á¸¦ ¹Þ´Â ÁßȯÀÚ¿¡¼­µµ º¼¼ö ÀÖ´Ù.

ƯÈ÷ multiple transfusion, Åõ¼®, TPNÀ» ½ÃÇàÇϴ ȯÀÚ, acute megaloblastic state´Â folate

ÀúÀåÀÌ ºÒÃæºÐÇÑ È¯ÀÚ¿¡¼­ weak antifolate(¿¹: trimethoprim)¸¦ Åõ¿©ÇÔÀ¸·Î½á ÃË¹ßµÉ ¼ö

ÀÖ´Ù.

ÀÌ »óȲÀº immune cytopenia¿Í À¯»çÇÏ¸ç ºóÇ÷ÀÌ ¾øÀÌ ºü¸£°Ô ¹ß»ýÇÏ´Â thrombocytopenia

and/or leukopenia¿Í À¯»çÇÏ´Ù. PB´Â ¿ÏÀüÈ÷ Á¤»óÀÌÁö¸¸ °ñ¼ö´Â megaloblasticÇÏ´Ù.

folate + cobalaminÄ¡·á¿¡ ºü¸£°Ô ¹ÝÀÀÇÑ´Ù.

2) cobalamin deficiency without anemia

³ëÀο¡¼­ ƯÈ÷ ÈçÇÏ´Ù. cobalaminÀÇ nonhematologic presentationÀ§ÇèÀº folate food¸¦

°­È­½ÃÅ´À¸·Î½á Áõ°¡µÉ¼ö Àִµ¥ ÀÌ´Â folate°¡ cobalamin deficiencyÀÇ hematologic effect

¸¦ maskÇÒ¼ö Àֱ⠶§¹®ÀÌ´Ù. 70¼¼ ÀÌ»óÀÇ 10-30%¿¡¼­ cobalamin deficiency¸¦ °¡Áö°í ÀÖ´Â

µ¥, homocysteine levelÁõ°¡, cobalamin-TC II level°¨¼Ò¸¦ º¸ÀδÙ. ÀÌ È¯ÀÚµé Áß ´ÜÁö 10%

¸¸ÀÌ IF»ý»ê¿¡ Àå¾Ö°¡ ÀÖÀ¸¸ç, ³ª¸ÓÁö´Â Á¾Á¾ atrophic gastritis¸¦ °¡Áö°í ÀÖ°í À½½ÄÀ¸·ÎºÎÅÍ

cobalaminÀ» À¯¸®ÇÒ¼ö ¾ø´Ù.

ÀÌ·¯ÇÑ È¯ÀÚµéÀº neuropsychiatric abnormality·Î ¹ßÇöÇϱ⵵ ÇÑ´Ù

: peripheral neuropathies, gait disturbance, memory loss & psychiatric sx.

serum cobalamin levelÀº Á¤»óÀ̰ųª ³·Áö¸¸, methylmalonic acid levelÀº °ÅÀÇ Ç×»ó Áõ°¡

µÇ¾î ÀÖ´Ù.

cobalaminÄ¡·áÈÄ neuropsychiatric abnormality°¡ È£ÀüµÇ°í serum methylmalonic acid level

ÀÌ Á¤»óÈ­µÈ´Ù. Neurologic deficit°¡ cobalaminÅõ¿©·Î Ç×»ó ȸº¹µÇ´Â °ÍÀº ¾Æ´Ï´Ù.

7. Áø´Ü

significant macrocytosis(MCV > 100fL)´Â megaloblastic anemia¸¦ ½Ã»çÇÑ´Ù.

macrocytosisÀÇ ´Ù¸¥ ¿øÀÎÀ¸·Î hemolysis, liver disease, alcoholism, hypothyroidism,

aplastic anemia°¡ ÀÖ´Ù.

macrocytosis°¡ ½ÉÇØÁö¸é(MCV > 110 fL) ȯÀÚ´Â ´õ¿í´õ megaloblastic anemia¸¦ °¡Áú °¡´É

¼ºÀÌ Ä¿Áø´Ù. reticulocyte count´Â ³·°í leukocyte & platelet count´Â ³·´Ù.

PB´Â ½ÉÇÑ anisocytosis, poikilocytosis, macroovalocyte¸¦ º¸À̸ç, Å©±â´Â Å©°í ³­¿øÇüÀ̸ç

¿ÏÀüÈ÷ hemoglobinized erythrocytes¸¦ º¸ÀδÙ. °¡²û basophilic stippling & nucleated RBC

¸¦ º¸ÀδÙ. ÇϳªÀÇ ¼¼Æ÷°¡ ¿©¼¸ ¿±ÀÇ ÇÙÀ» °¡Áö´Â Ư¡Àû ¼Ò°ßÀÌ Àִµ¥ ÀÌ´Â megaloblastic

anemia¸¦ ¹Ù·Î ÀǽÉÇÒ ¼ö ÀÖ°Ô ÇÑ´Ù. reti count´Â ³·´Ù.

BM´Â hypercellular & M/E ratio°¨¼Ò, ¸¹Àº stainable ironÀ» º¸ÀδÙ.

RBC precursor´Â ºñÁ¤»óÀûÀ¸·Î Å©°í, cytoplasm¿¡ ºñÇØ ´ú ¼º¼÷ÇÑ ÇÙÀ» °¡Áø´Ù

(nuclear-cytoplasmic asynchrony). megaloblastic anemia´Â ineffective erythropoiesis°¡

Ư¡ÀÌ´Ù. RBC precursorÀÇ 90%Ç÷ÁßÀ¸·Î ³ª°¡±â Àü¿¡ ÆÄ±«µÈ´Ù(Á¤»óÀÎÀº 10-15%).

erythroblastÀÇ °ñ¼ö³» ÆÄ±«·Î ÀÎÇÏ¿© unconjugated bilirubin°ú LDH(iso 1)°¡ Áõ°¡ÇÑ´Ù.

megaloblastic anemiaȯÀÚ¸¦ Æò°¡Çϴµ¥ serum cobalamin°ú folate levelÀ» ÃøÁ¤ÇÔÀ¸·Î½á

¾î´À vitamin°áÇÌÀÎÁö °áÁ¤ÇÏ´Â °ÍÀº Áß¿äÇÏ´Ù.

cobalaminÀÇ Á¤»ó¹üÀ§´Â 200-900 pg/mlÀε¥ 100 pg/ml¹Ì¸¸À϶§´Â significant deficiency¸¦

ÀǹÌÇÑ´Ù. TC II¿¡ °áÇÕµÈ cobalaminÀÇ ÃøÁ¤ÀÌ º¸´Ù »ý¸®ÀûÀÎ ÃøÁ¤ÀÌÁö¸¸ ÀÌ´Â ¾ÆÁ÷ º¸ÆíÀû

À¸·Î »ç¿ëµÇÁö´Â ¾Ê´Â´Ù.

folic acidÀÇ Á¤»ó³óµµ´Â 6-20 ng/mlÀÌ´Ù. 4 ng/mlÀÌÇÏÀ϶§´Â ÀϹÝÀûÀ¸·Î folate deficiency

Áø´ÜÀ» °í·ÁÇÒ¼ö ÀÖ´Ù. serum cobalamin°ú ´Þ¸® serum folate levelÀº ÃÖ±ÙÀÇ ½ÄÀÌ ¼·Ã븦

¹Ý¿µÇÑ´Ù. RBC folateÀÇ ÃøÁ¤Àº short-term fluctuationµÇÁö ¾ÊÀ¸¹Ç·Î folate intakeÀÇ À¯¿ëÇÑ

Á¤º¸¸¦ Á¦°øÇϰí folate ÀúÀåÀÇ ÁöÇ¥·Î¼­ serum folateº¸´Ù ³´´Ù.

ÀÏ´Ü cobalamin deficiency°¡ È®ÀÎµÇ¸é º´ÀÎÀº Schilling test¿¡ ÀÇÇØ °áÁ¤ÇÑ´Ù. °æ±¸·Î

radioactive cobalaminÀ» ¸ÔÀºÈÄ unlabeled cobalaminÀ» IMÇÑ´Ù.

24½Ã°£µ¿¾È ¼Òº¯À¸·Î ¹è¼³µÇ´Â radioactivityÀÇ ºñ°¡ Èí¼öµÇ´Â Á¤È®ÇÑ ¾çÀ» ÀǹÌÇÑ´Ù.

cobalamin deficiency´Â °ÅÀÇ Ç×»ó malabsorption¿¡ ÀÇÇϹǷΠSchilling testÀÇ 1st stage°¡ ºñ

Á¤»óÀÏ °ÍÀÌ´Ù. ÀÌ È¯ÀÚ´Â IF¿¡ °áÇÕµÈ labeled cobalaminÀ» Åõ¿©ÇÑ´Ù. pernicious anemia¿Í

´Ù¸¥ ÇüÅÂÀÇ IF deficiency¶ó¸é vitaminÈí¼ö´Â Á¤»óÀûÀÏ °ÍÀÌ´Ù.

¸¸¾à cobalaminÈí¼ö°¡ ¿©ÀüÈ÷ °¨¼ÒÇϸé ȯÀÚ´Â bacterial overgrowth(blind loop syndrome)

or ileal disease¸¦ °¡Áö°í ÀÖÀ» °ÍÀÌ´Ù.

bacterial overgrowth¿¡ ÀÇÇÑ cobalamin malabsorptionÀº ÈçÈ÷ Ç×»ýÁ¦ Åõ¿©·Î ±³Á¤ÇÒ¼ö ÀÖ´Ù.

Shilling test´Â ȯÀÚ°¡ °æÇÇÀû cobalaminÄ¡·áÈÄ¿¡ À¯¿ëÇÑ Á¤º¸¸¦ Á¦°øÇÒ¼ö ÀÖ´Ù.

serum methylmalonic acid & homocysteine levelsÀº ¶ÇÇÑ megaloblastic anemiaÁø´Ü¿¡ À¯¿ë

ÇÏ´Ù. cobalamin deficiency¶§´Â µÑ´Ù Áõ°¡ÇÏÁö¸¸ folate deficiency¶§´Â homocysteine level

¸¸ Áõ°¡ÇÑ´Ù.

8. Ä¡·á

1) Cobalamin deficiency

Àå³»¼¼±ÕÁõ½Ä¿¡ ´ëÇØ Ç×»ýÁ¦¸¦ ¾²´Â °ÍÀ» Á¦¿ÜÇϰí´Â cobalamin deficiency Ä¡·áÀÇ ±âº»Àº

replacement txÀÌ´Ù. cobalamin °áÇÌÀº °ÅÀÇ Ç×»ó malabsorption¿¡ ÀÇÇϹǷΠȯÀÚ´Â ÀϹÝÀû

À¸·Î parenteral tx(º¸Åë IM cyanocobalamin)ÇÑ´Ù.

*100ug ÁÖ1ȸ ¡¿ 8ÁÖ -> ±×ÈÄ 1000 ug ¿ù1ȸ Æò»ý

±×·¯³ª 2mg crystalline B12 ¸ÅÀÏ POÇϴ°͵µ ¸Å¿ì È¿°úÀûÀÌ´Ù.

Ä¡·áÈÄ marrow morphology´Â ¼ö½Ã°£ÈÄ Á¤»óÈ­µÇ¸ç reticulocytosis´Â 4-5ÀÏÈÄ ½ÃÀ۵Ǿî

7Àϰ ÃÖ°íÁ¶¿¡ ´ÞÇÑ´Ù(Fig 107-3). ±×ÈÄ ¼öÁÖ¿¡ °ÉÃÄ ºóÇ÷Àº ȸº¹µÈ´Ù.

reticulocytosis°¡ ÀϾÁö ¾Ê°Å³ª Hct°¡ ±â´ë¼öÁØÀ¸·Î µµ´ÞÇÏÁö ¾ÊÀ¸¸é ºóÇ÷¿¡ ±â¿©ÇÏ´Â

ÀÎÀÚ¸¦ Á¶»çÇØ¾ß ÇÑ´Ù.

(¿¹: °¨¿°, µ¿¹ÝµÈ iron deficiency, folate deficiency or hypothyroidism)

Ä¡·áÃʱ⿡ hypokalemia & salt retentionÀÌ »ý±æ¼ö ÀÖÀ¸¸ç thrombocytosisµµ º¼¼ö ÀÖ´Ù.

´ë·®ÀÇ folate°¡ cobalamin deficiency·Î ÀÎÇÑ megaloblastic anemia¸¦ ±³Á¤ÇÒ¼ö ÀÖ´Ù(½Å°æÇÐ

Àû ÀÌ»ó Á¦¿Ü).

folate tx·Î ½Å°æÇÐÀû Áõ»óÀº ¾ÇÈ­µÇ±âµµ ÇÑ´Ù. ´ë·®ÀÇ folate Åõ¿©È¯ÀÚ¿¡¼­ cobalamin

deficiency°¡ maskµÉ¼ö ÀÖ´Ù. ÀÌ·± ÀÌÀ¯·Î folate Åõ¿©·Î hematologic response¸¦ º¸Àδٰí

ÇØ¼­ cobalamin deficiency¸¦ ¹èÁ¦ÇÏ¸é ¾ÈµÈ´Ù.

cobalamin deficiency´Â ´ÜÁö ÀûÀýÇÑ °Ë»ç°á°ú·Î ¹èÁ¦ÇØ¾ß ÇÑ´Ù. ³ëÀο¡¼­ cobalamin Èí¼ö

Àå¾Ö ºóµµ°¡ ³ô°í Ç÷¾×ÇÐÀû Áõ»óº¸´Ù ½Å°æÇÐÀû Áõ»óÀ¸·Î ¹ßÇöµÇ´Â overt cobalamin

deficiencyÀ§ÇèÀÌ Áõ°¡ÇϹǷΠÀϺÎÀü¹®°¡´Â 65¼¼ ÀÌ»ó ³ëÀο¡°Ô 0.1mg/d oral crystalline

cobalamin prophylaxis¸¦ ±ÇÀ¯Çϱ⵵ ÇÑ´Ù.

2) folate deficiency

¿ª½Ã replacement txÇÑ´Ù.

1mg/d PO(Åë»ó¿ë·®), ±×·¯³ª Èí¼öÀå¾ÖÀÎ °æ¿ì °í¿ë·®(¡­5mg/d)ÀÌ ÇÊ¿äÇÒ¼ö ÀÖ´Ù.

Ä¡·áÈÄ hematologic response´Â cobalamin deficiency¿Í À¯»çÇÏ´Ù.

Ä¡·á±â°£Àº °áÇÌ»óÅ¿¡ µû¶ó °áÁ¤ÇÑ´Ù.

3)´Ù¸¥ ¿øÀÎ

¾à¿¡ ±âÀÎÇÑ °æ¿ì ÇÊ¿äÇÏ¸é ¾àÀ» ÁÙÀ̰ųª Áß´ÜÇÔÀ¸·Î½á Ä¡·áÇÒ¼ö ÀÖ´Ù.

folate antagonist(DHF reductase inhibitor)ÀÇ ¿µÇâÀº folinic acid(5-THF)

100-200 mg/d¸¦ Åõ¿©ÇÔÀ¸·Î½á »ó¼âµÉ¼ö ÀÖ´Ù.