案例#1
一名 60 岁的白人男性,既往有明显的 Graves 病史2个月内出现体重减轻 4.5 千克、双下肢感觉异常伴无力以及步态不稳。查体:结膜苍白、舌光滑、振动感觉受损和共济失调。实验室检测结果为显著的巨幼红细胞性贫血、低血清钴胺素(维生素 B12)和抗壁细胞抗体阳性。食管胃十二指肠镜检查(OGD 或上消化道内窥镜检查)显示胃底和胃体黏膜(泌酸黏膜)皱襞消失,黏膜下血管易见。胃液检查提示 pH 值>6.0。活检显示萎缩性胃炎,伴灶性肠上皮化生且无幽门螺杆菌感染。
案例#2
一名活跃的 79 岁的女性,近 6 个月以来出现进行性无力和运动不耐受。除甲床苍白外,体检无其它明显异常体征。实验室检测结果显示,小细胞低色素性贫血、血红蛋白 8 g/dL、血清铁降低(10 µg/dL)、低转铁蛋白饱和度 (4%) 和低铁蛋白(10 ng/mL)。除憩室外,结肠镜检查结果为阴性。OGD 显示胃体部皱襞消失, 3 个无蒂息肉,各<1 cm,表面被覆正常黏膜。胃体活检显示胃腺体完全消失。结节活检:核圆、均质、分化良好的卵圆细胞。此细胞利用 Grimelius 和 Sevier-Munger 染色方法均提示细胞具有嗜银性;此外,嗜铬粒蛋白 A 和组胺免疫染色结果也均为阳性。血清胃泌素,并升高至1000 pg/mL。
其他表现
胃酸缺乏患者通常无症状。因为胃酸促进非血红素铁(可能也有血红素铁)、钴胺素(维生素 B12)及钙(可能)的吸收,患者可能存在这些营养素缺乏引起的体征和症状。[9]Betesh AL, Santa Ana CA, Cole JA, et al. Is achlorhydria a cause of iron deficiency anemia? Am J Clin Nutr. 2015;102:9-19.http://www.ajcn.org/cgi/pmidlookup?view=long&pmid=25994564http://www.ncbi.nlm.nih.gov/pubmed/25994564?tool=bestpractice.com此外,萎缩性胃炎患者缺乏内因子(钴胺素吸收所必需的、主要由壁细胞分泌的一种蛋白)。[10]Howard TA, Misra DN, Grove M, et al. Human gastric intrinsic factor expression is not restricted to parietal cells. J Anat. 1996;189:303-313.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1167747/pdf/janat00124-0047.pdfhttp://www.ncbi.nlm.nih.gov/pubmed/8886952?tool=bestpractice.com几项流行病学研究表明,质子泵抑制剂的使用以及恶性贫血的诊断与骨质疏松相关的髋部骨折风险显著增加相关。[11]Richards JB, Goltzman D. Proton-pump inhibitors: balancing the benefits and potential fracture risks. CMAJ. 2008;179:306-307.http://www.cmaj.ca/content/179/4/306.fullhttp://www.ncbi.nlm.nih.gov/pubmed/18695170?tool=bestpractice.com[12]Yang YX, Lewis JD, Epstein S, et al. Long-term proton-pump inhibitor therapy and risk of hip fracture. JAMA. 2006;296:2947-2953.http://www.ncbi.nlm.nih.gov/pubmed/17190895?tool=bestpractice.com[13]Targownik LE, Lix LM, Metge CJ, et al. Use of proton-pump inhibitors and risk of osteoporosis-related fractures. CMAJ. 2008;179:319-326.http://www.cmaj.ca/content/179/4/319.fullhttp://www.ncbi.nlm.nih.gov/pubmed/18695179?tool=bestpractice.com胃酸分泌不足也可能与肠道感染相关,包括社区获得性和医院获得性艰难梭菌相关疾病、沙门氏菌和弯曲杆菌以及细菌过度生长;[14]Friis-Hansen L. Achlorhydria is associated with gastric microbial overgrowth and development of cancer: lessons learned from the gastrin knockout mouse. Scand J Clin Lab Invest. 2006;66:607-621.http://www.ncbi.nlm.nih.gov/pubmed/17101553?tool=bestpractice.com[15]Pohl D, Fox M, Fried M, et al. Do we need gastric acid? Digestion. 2008;77:184-197.http://www.ncbi.nlm.nih.gov/pubmed/18594142?tool=bestpractice.com[16]Williams C, McColl KE. Review article: proton-pump inhibitors and bacterial overgrowth. Aliment Pharmacol Ther. 2006;23:3-10.http://www.ncbi.nlm.nih.gov/pubmed/16393275?tool=bestpractice.com[17]Leonard J, Marshall JK, Moayyedi P. Systematic review of the risk of enteric infection in patients taking acid suppression. Am J Gastroenterol. 2007;102:2047-2056.http://www.ncbi.nlm.nih.gov/pubmed/17509031?tool=bestpractice.com[18]Dial S, Delaney JA, Barkun AN, et al. Use of gastric acid-suppressive agents and the risk of community-acquired Clostridium difficile-associated disease. JAMA. 2005;294:2989-2995.http://www.ncbi.nlm.nih.gov/pubmed/16414946?tool=bestpractice.com[19]Gulmez SE, Holm A, Frederiksen H, et al. Use of proton-pump inhibitors and the risk of community-acquired pneumonia: a population-based case-control study. Arch Intern Med. 2007;167:950-955.http://www.ncbi.nlm.nih.gov/pubmed/17502537?tool=bestpractice.com[20]Sarkar M, Hennessy S, Yang YX. Proton-pump inhibitor use and the risk for community-acquired pneumonia. Ann Intern Med. 2008;149:391-398.http://www.ncbi.nlm.nih.gov/pubmed/18794558?tool=bestpractice.com后者可能导致轻度脂肪吸收障碍,且可能通过减少维生素 D 的吸收加剧钙缺乏。