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blood cells that engulf and digest bacteria and fungi; an important part of the bodys defense system (同)leucocyte, white_blood_cell, white_cell, white blood corpuscle, white_corpuscle, WBC

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/03/04 07:49:38」(JST)

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White blood cells (WBCs), also called leukocytes or leucocytes, are the cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All leukocytes are produced and derived from a multipotent cell in the bone marrow known as a hematopoietic stem cell. Leukocytes are found throughout the body, including the blood and lymphatic system.^[1]

Five^[2] different and diverse types of leukocytes exist. These types are distinguished by their physical and functional characteristics. Monocytes and neutrophils are phagocytic.

The number of leukocytes in the blood is often an indicator of disease. The normal white cell count is usually between 4 and 11 × 10⁹/L. In the US this is usually expressed as 4000–11,000 white blood cells per microliter of blood.^[3] They make up approximately 1% of the total blood volume in a healthy adult.^[4] An increase in the number of leukocytes over the upper limits is called leukocytosis, and a decrease below the lower limit is called leukopenia.

1 Etymology
2 Types
- 2.1 Overview
- 2.2 Neutrophil
- 2.3 Eosinophil
- 2.4 Basophil
- 2.5 Lymphocyte
- 2.6 Monocyte
3 Fixed leukocytes
4 Disorders
- 4.1 Leukopenias
  - 4.1.1 Neutropenia
  - 4.1.2 Lymphocytopenia
- 4.2 Proliferative disorders
  - 4.2.1 Neutrophilia
  - 4.2.2 Eosinophilia
5 Counting and reference ranges
6 See also
7 References
8 External links

Etymology

The name "white blood cell" derives from the physical appearance of a blood sample after centrifugation. White cells are found in the buff, a thin, typically white layer of nucleated cells between the sedimented red blood cells and the blood plasma. The scientific term leukocyte directly reflects its description. It is derived from the Greek word leuko- meaning "white" and kytos meaning "hollow vessel", with -cyte translated as "cell" in modern use. Buffy coat may sometimes be green if there are large amounts of neutrophils in the sample, due to the heme-containing enzyme myeloperoxidase that they produce.

Types

3D rendering of various types of white blood cells

All white blood cells are nucleated but are otherwise distinct in form and function. White cells are best classified into two major lineages: the myeloid leukocytes and the lymphocytes.^[5]

The white cells of the myeloid lineage include neutrophils, monocytes, eosinophils and basophils.

Lymphocytes include T cells, B cells and natural killer cells.

Overview

Type	Approx. % in adults ^{See also:} Blood values	Diameter (μm)^[6]	Main targets^[4]	Nucleus^[4]	Granules^[4]	Lifetime^[6]
Neutrophil	62%	10–12	Bacteria Fungi	Multilobed	Fine, faintly pink (H&E stain)	6 hours–few days (days in spleen and other tissue)
Eosinophil	2.3%	10–12	Larger parasites Modulate allergic inflammatory responses	Bi-lobed	Full of pink-orange (H&E stain)	8–12 days (circulate for 4–5 hours)
Basophil	0.4%	12–15	Release histamine for inflammatory responses	Bi-lobed or tri-lobed	Large blue	A few hours to a few days
Lymphocyte	30%	Small lymphocytes 7–8 Large lymphocytes 12–15	B cells: releases antibodies and assists activation of T cells T cells: CD4+ Th (T helper) cells: activate and regulate T and B cells CD8+ cytotoxic T cells: virus-infected and tumor cells. γδ T cells: bridge between innate and adaptive immune responses; phagocytosis Regulatory (suppressor) T cells: Returns the functioning of the immune system to normal operation after infection; prevents autoimmunity Natural killer cells: virus-infected and tumor cells.	Deeply staining, eccentric	NK-cells and cytotoxic (CD8+) T-cells	Years for memory cells, weeks for all else.
Monocyte	5.3%	12–15^[7]	Monocytes migrate from the bloodstream to other tissues and differentiate into tissue resident macrophages, Kupffer cells in the liver.	Kidney shaped	None	Hours to days

Neutrophil

Neutrophil engulfing anthrax bacteria

Neutrophils are the most abundant white blood cell, constituting 60-70% of the circulating leukocytes. They defend against bacterial or fungal infection. They are usually first responders to microbial infection; their activity and death in large numbers forms pus. They are commonly referred to as polymorphonuclear (PMN) leukocytes, although, in the technical sense, PMN refers to all granulocytes. They have a multi-lobed nucleus, which consists of three to five lobes connected by slender strands.^[8] This gives the neutrophils the appearance of having multiple nuclei, hence the name polymorphonuclear leukocyte. The cytoplasm may look transparent because of fine granules that are pale lilac when stained. Neutrophils are active in phagocytosing bacteria and are present in large amount in the pus of wounds. These cells are not able to renew their lysosomes (used in digesting microbes) and die after having phagocytosed a few pathogens.^[9] Neutrophils are the most common cell type seen in the early stages of acute inflammation. They make up 60-70% of total leukocyte count in human blood.^[4] The life span of a circulating human neutrophil is about 5.4 days.^[10]

Eosinophil

Eosinophils compose about 2-4% of the WBC total. This count fluctuates throughout the day, seasonally, and during menstruation. It rises in response to allergies, parasitic infections, collagen diseases, and disease of the spleen and central nervous system. They are rare in the blood, but numerous in the mucous membranes of the respiratory, digestive, and lower urinary tracts.^[8]

They primarily deal with parasitic infections. Eosinophils are also the predominant inflammatory cells in allergic reactions. The most important causes of eosinophilia include allergies such as asthma, hay fever, and hives; and also parasitic infections. They secrete chemicals that destroy these large parasites, such as hook worms and tapeworms, that are too big for any one WBC to phagocytize. In general, their nucleus is bi-lobed. The lobes are connected by a thin strand.^[8] The cytoplasm is full of granules that assume a characteristic pink-orange color with eosin staining.

Basophil

Basophils are chiefly responsible for allergic and antigen response by releasing the chemical histamine causing the dilation of blood vessels. Because they are the rarest of the white blood cells (less than 0.5% of the total count) and share physicochemical properties with other blood cells, they are difficult to study.^[11] They can be recognized by several coarse, dark violet granules, giving them a blue hue. The nucleus is bi- or tri-lobed, but it is hard to see because of the number of coarse granules that hide it.

They excrete two chemicals that aid in the body's defenses: histamine and heparin. Histamine is responsible for widening blood vessels and increasing the flow of blood to injured tissue. It also makes blood vessels more permeable so neutrophils and clotting proteins can get into connective tissue more easily. Heparin is an anticoagulant that inhibits blood clotting and promotes the movement of white blood cells into an area. Basophils can also release chemical signals that attract eosinophils and neutrophils to an infection site.^[8]

Lymphocyte

Lymphocytes are much more common in the lymphatic system than in blood. Lymphocytes are distinguished by having a deeply staining nucleus that may be eccentric in location, and a relatively small amount of cytoplasm. Lymphocytes include:

B cells make antibodies that can bind to pathogens, block pathogen invasion, activate the complement system, and enhance pathogen destruction.
T cells:
- CD4+ helper T cells: T cells displaying co-receptor CD4 are known as CD4+ T cells. These cells have T-cell receptors and CD4 molecules that, in combination, bind antigenic peptides presented on major histocompatibility complex (MHC) class II molecules on antigen-presenting cells. Helper T cells make cytokines and perform other functions that help coordinate the immune response. In HIV infection, these T cells are the main index to identify the individual's immune system integrity.
- CD8+ cytotoxic T cells: T cells displaying co-receptor CD8 are known as CD8+ T cells. These cells bind antigens presented on MHC I complex of virus-infected or tumour cells and kill them. Nearly all nucleated cells display MHC I.
- γδ T cells possess an alternative T cell receptor (different from the αβ TCR found on conventional CD4+ and CD8+ T cells). Found in tissue more commonly than in blood, γδ T cells share characteristics of helper T cells, cytotoxic T cells, and natural killer cells.
Natural killer cells are able to kill cells of the body that do not display MHC class I molecules, or display stress markers such as MHC class I polypeptide-related sequence A (MIC-A). Decreased expression of MHC class I and up-regulation of MIC-A can happen when cells are infected by a virus or become cancerous.

Monocyte

Monocytes share the "vacuum cleaner" (phagocytosis) function of neutrophils, but are much longer lived as they have an extra role: they present pieces of pathogens to T cells so that the pathogens may be recognized again and killed. This causes an antibody response to be mounted. Monocytes eventually leave the bloodstream and become tissue macrophages, which remove dead cell debris as well as attacking microorganisms. Neither dead cell debris nor attacking microorganisms can be dealt with effectively by the neutrophils. Unlike neutrophils, monocyte are able to replace their lysosomal contents and are thought to have a much longer active life. They have the kidney shaped nucleus and are typically agranulated. They also possess abundant cytoplasm.

Once monocyte move from the bloodstream out into the body tissues, they undergo changes (differentiate) allowing phagocytosis and are then known as macrophages.

Fixed leukocytes

HSC=Hematopoietic stem cell, Progenitor=Progenitor cell, L-blast=Lymphoblast, Lymphocyte, Mo-blast=Monoblast, Monocyte, Myeloblast, Pro-M=Promyelocyte, Myelocyte, Meta-M=Metamyelocyte, Neutrophil, Eosinophil, Basophil, Pro-E=Proerythroblast, Baso-E=Basophilic erythroblast, poly-E=Polychromatic erythroblast, Ortho-E=Orthochromatic erythroblast, Erythrocyte, Promegakaryocyte, Megakaryocyte, Platelet

Some leukocytes migrate into the tissues of the body to take up a permanent residence at that location rather than remaining in the blood. Often these cells have specific names depending upon which tissue they settle in, such as fixed macrophages in the liver, which become known as Kupffer cells. These cells still serve a role in the immune system.

Histiocytes
Dendritic cells (Although these will often migrate to local lymph nodes upon ingesting antigens)
Mast cells
Microglia

Disorders

There are two major categories of white blood cell disorders: proliferative and leukopenias.^[12] In the proliferative disorders there is an increase in the number of white blood cells. This increase is commonly reactive (ex. due to infection) but may also be cancerous. In leukopenias there is a decrease in the number of white blood cells. Both proliferative disease and leukopenias are quantitative disorders of white blood cells. Qualitative disorders of white blood cells are another category. These are disorders in which the number of white blood cells is normal but the cells do not function normally.^[13]

Leukopenias

A range of disorders can cause decreases in white blood cells. This type of white blood cell decreased is usually the neutrophil. In this case the decrease may be called neutropenia or granulocytopenia. Less commonly, a decrease in lymphocytes (called lymphocytopenia or lymphopenia) may be seen.^[12]

Neutropenia

Neutropenia can be acquired or intrinsic.^[14] A decrease in levels of neutrophils on lab tests is due to either decreased production of neutrophils or increased removal from the blood.^[12] The following list of causes is not complete.

Medications - chemotherapy, sulfas or other antibiotics, phenothiazenes, benzodiazepines, antithyroids, anticonvulsants, quinine, quinidine, indomethacin, procainamide, thiazides
Radiation
Toxins - alcohol, benzenes
Intrinsic disorders - Fanconi's, Kostmann's, cyclic neutropenia, Chediak-Higashi
Immune dysfunction - disorders of collagen, AIDS, rheumatoid arthritis
Blood cell dysfunction - megaloblastic anemia, myelodysplasia, marrow failure, marrow replacement, acute leukemia
Any major infection
Miscellaneous - starvation, hypersplenism

Symptoms of neutropenia are associated with the underlying cause of the decrease in neutrophils. For example, the most common cause of acquired neutropenia is drug-induced, so an individual may have symptoms of medication overdose or toxicity. Treatment is also aimed at the underlying cause of the neutropenia.^[15] One severe consequence of neutropenia is that it can increase the risk of infection.^[13]

Lymphocytopenia

Defined as total lymphocyte count below 1.0x10⁹/L, the cells most commonly affected are CD4+ T cells. Like neutropenia, lymphocytopenia may be acquired or intrinsic and there are many causes.^[13] This is not a complete list.

Inherited immune deficiency - severe combined immunodeficiency, common variable immune deficiency, ataxia-telangiectasia, Wiskott-Aldrich syndrome, immunodeficiency with short-limbed dwarfism, immunodeficiency with thymoma, purine nucleoside phosphorylase deficiency, genetic polymorphism
Blood cell dysfunction - aplastic anemia
Infectious diseases - viral (AIDS, SARS, West Nile encephalitis, hepatitis, herpes, measles, others), bacterial (TB, typhoid, pneumonia, rickettsiosis, ehrlichiosis, sepsis), parasitic (acute phase of malaria)
Medications - chemotherapy (antilymphocyte globulin therapy, alemtuzumab, glucocorticoids)
Radiation
Major surgery
Miscellaneous - ECMO, kidney or bone marrow transplant, hemodialysis, kidney failure, severe burn, celiac disease, severe acute pancreatitis, sarcoidosis, protein-losing enteropathy, strenuous exercise, carcinoma
Immune dysfunction - arthritis, systemic lupus erythematosus, Sjogren syndrome, myasthenia gravis, systemic vasculitis, Behcet-like syndrome, dermatomyositis, Wegener granulomatosis
Nutritional/Dietary - alcohol abuse, zinc deficiency

Like neutropenia, symptoms and treatment of lymphocytopenia are directed at the underlying cause of the change in cell counts.

Proliferative disorders

An increase in the number of white blood cells in circulation is called leukocytosis.^[12] This increase is most commonly caused by inflammation.^[12] There are four major causes: increase of production in bone marrow, increased release from storage in bone marrow, decreased attachment to veins and arteries, decreased uptake by tissues.^[12] Leukocytosis may affect one or more cell lines and can be neutrophilic, eosinophilic, basophilic, monocytosis, or lymphocytosis.

Neutrophilia

Neutrophilia is an increase in the absolute neutrophil count in the peripheral circulation. Normal blood values vary by age.^[13] Neutrophilia can be caused by a direct problem with blood cells (primary disease). It can also occur as a consequence of an underlying disease (secondary). Most cases of neutrophilia are secondary to inflammation.^[15]

Primary causes^[15]

Conditions with normally functioning neutrophils – hereditary neutrophilia, chronic idiopathic neutrophilia
Pelger–Huet anomaly
Down syndrome
Leukocyte adhesion deficiency
Familial cold urticaria
Leukemia (chronic myelogenous (CML)) and other myeloproliferative disorders
Surgical removal of spleen^[16]

Secondary causes^[15]

Infection
Chronic inflammation – especially juvenile rheumatoid arthritis, rheumatoid arthritis, Still's disease^{[disambiguation needed]}, Crohn's disease, ulcerative colitis, granulomatous infections (for example, tuberculosis), and chronic hepatitis
Cigarette smoking – occurs in 25–50% of chronic smokers and can last up to 5 years after quitting
Stress – exercise, surgery, general stress
Medication induced – corticosteroids (for example, prednisone, β-agonists, lithium)
Cancer – either by growth factors secreted by the tumor or invasion of bone marrow by the cancer
Increased destruction of cells in peripheral circulation can stimulate bone marrow. This can occur in hemolytic anemia and idiopathic thrombocytopenic purpura

Eosinophilia

A normal eosinophil count is considered to be less than 0.65×10⁹/L.^[13] Eosinophil counts are higher in newborns and vary with age, time (lower in the morning and higher at night), exercise, environment, and exposure to allergens.^[13] Eosinophilia is never a normal lab finding. Efforts should always be made to discover the underlying cause, though the cause may not always be found.^[13]

Counting and reference ranges

The complete blood cell count is a blood panel that includes the overall WBC count and various subsets such as the absolute neutrophil count. Reference ranges for blood tests specify the typical counts in healthy people.

References

^ Maton, D., Hopkins, J., McLaughlin, Ch. W., Johnson, S., Warner, M. Q., LaHart, D., & Wright, J. D., Deep V. Kulkarni (1997). Human Biology and Health. Englewood Cliffs, New Jersey, US: Prentice Hall. ISBN 0-13-981176-1.
^ LaFleur-Brooks, M. (2008). Exploring Medical Language: A Student-Directed Approach (7th ed.). St. Louis, Missouri, US: Mosby Elsevier. p. 398. ISBN 978-0-323-04950-4.
^ "Vital and Health Statistics Series 11, No. 247 (03/2005)" (PDF). Retrieved 2014-02-02.
^ ^a ^b ^c ^d ^e Bruce Alberts, Alexander Johnson, Julian Lewis, Martin Raff, Keith Roberts, and Peter Walter (2002). "Leukocyte functions and percentage breakdown". Molecular Biology of the Cell (4th ed.). New York: Garland Science. ISBN 0-8153-4072-9.
^ Orkin, SH; Zon, LI (Feb 22, 2008). "SnapShot: hematopoiesis.". Cell 132 (4): 712. PMID 18295585.
^ ^a ^b Daniels, V. G., Wheater, P. R., & Burkitt, H.G. (1979). Functional histology: A text and colour atlas. Edinburgh: Churchill Livingstone. ISBN 0-443-01657-7.
^ Handin, Robert I.; Samuel E. Lux; Thomas P. Stossel (2003). Blood: Principles and Practice of Hematology (2nd ed.). Philadelphia: Lippincott Williams and Wilkins. p. 471. ISBN 9780781719933. Retrieved 2013-06-18.
^ ^a ^b ^c ^d Saladin, Kenneth (2012). Anatomy and Physiology: the Unit of Form and Function (6 ed.). New York: McGraw Hill. ISBN 978-0-07-337825-1.
^ Wheater, Paul R.; Stevens, Alan (2002). Wheater's basic histopathology: a colour atlas and text. Edinburgh: Churchill Livingstone. ISBN 0-443-07001-6.
^ Pillay, J.; Den Braber, I.; Vrisekoop, N.; Kwast, L. M.; De Boer, R. J.; Borghans, J. A. M.; Tesselaar, K.; Koenderman, L. (2010). "In vivo labeling with 2H2O reveals a human neutrophil lifespan of 5.4 days". Blood 116 (4): 625–7. doi:10.1182/blood-2010-01-259028. PMID 20410504.
^ Falcone, Franco; Haas, Helmut; Gibbs, Bernard (15 December 2000). "The human basophil: a new appreciation of its role in immune responses.". Blood 96 (13): 4028–38. PMID 11110670.
^ ^a ^b ^c ^d ^e ^f Vinay Kumar et al. (2010). Robbins and Cotran pathologic basis of disease. (8th ed.). Philadelphia, PA: Saunders/Elsevier. ISBN 1416031219.
^ ^a ^b ^c ^d ^e ^f ^g Kenneth Kaushansky et al., ed. (2010). Williams hematology (8th ed.). New York: McGraw-Hill Medical. ISBN 0071621512.
^ Richard A. McPherson, Matthew R. Pincus, Naif Z. Abraham Jr. et al. (ed.). Henry's clinical diagnosis and management by laboratory methods (22nd ed.). Philadelphia, PA: Elsevier/Saunders. ISBN 1437709745.
^ ^a ^b ^c ^d Lee Goldman; Andrew I. Schafer (eds.). Goldman's Cecil medicine (24th ed.). Philadelphia: Elsevier/Saunders. ISBN 1437716040.
^ McBride, JA; Dacie, JV; Shapley, R (Feb 1968). "The effect of splenectomy on the leucocyte count.". British journal of haematology 14 (2): 225–31. PMID 5635603.

External links

Atlas of Hematology
Leukocytes at the US National Library of Medicine Medical Subject Headings (MeSH)

UpToDate Contents

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1. 白血球増多症および好中球増多症の定義およびメカニズム definition and mechanisms of leukocytosis and neutrophilia
2. 成人の尿路感染症の診断における排出尿採取および評価 sampling and evaluation of voided urine in the diagnosis of urinary tract infection in adults
3. Leukocyte-adhesion deficiency
4. 下肢末梢動脈疾患の症状を治療するための試験的治療 investigational therapies for treating symptoms of lower extremity peripheral artery disease
5. Diagnosis of celiac disease in children

English Journal

Evaluation of a replacement method for mammary gland biopsies by comparing gene expression in udder tissue and mammary epithelial cells isolated from milk.

Krappmann K, Weikard R, Kühn C.SourceRes. Unit Molecular Biology, Leibniz Institute for Farm Animal Biology (FBN), Wilhelm-Stahl-Allee 2, 18196 Dummerstorf, Germany.
Research in veterinary science.Res Vet Sci.2012 Oct;93(2):970-4. Epub 2012 Jan 21.
Somatic cells isolated from milk offer an attractive non-invasive replacement of invasive udder biopsies for monitoring bovine mammary gland metabolism. However, for metabolic gene expression studies the mammary gland epithelial cells (MEC) isolated from milk have to be purified from the non-epithel
PMID 22265217

Atherogenic and pulmonary responses of ApoE- and LDL receptor-deficient mice to sidestream cigarette smoke.

Han SG, Howatt DA, Daugherty A, Gairola CG.SourceGraduate Center for Toxicology, University of Kentucky, Lexington, KY, USA; Department of Animal and Food Sciences, University of Kentucky, Lexington, KY, USA.
Toxicology.Toxicology.2012 Sep 28;299(2-3):133-8. Epub 2012 Jun 1.
Plasma lipoproteins play important roles in the development and progression of atherosclerosis. Two widely used mouse models of experimental atherosclerosis, apolipoprotein E-deficient (ApoE -/-) and LDL receptor-deficient (LDLr -/-) mice, have major differences in lipoprotein characteristics. These
PMID 22659316

Japanese Journal

Successful treatment of Trichosporon fungemia in a patient with refractory acute myeloid leukemia using voriconazole combined with liposomal amphotericin B

Hosokawa Kohei,Yamazaki Hiroto,Mochizuki K.,Ohata K.,Ishiyama K.,Hayashi Tomoe,Kondo Y.,Sugimori Naomi,Okumura H.,Takami Akiyoshi,Nakao Shinji
Transplant Infectious Disease 14(2), 184-187, 2012-04
… Although two courses of induction therapy failed to induce a remission of AML, combination therapy with voriconazole and liposomal amphotericin B (L-AmB) followed by monocyte colony-stimulating factor ameliorated the Trichosporon fungemia and enabled the patient to receive reduced-intensity bone marrow transplantation (BMT) from his human leukocyte antigen-A one-locus mismatched mother. …
NAID 120003989036

Creation of a blood-compatible surface: A novel strategy for suppressing blood activation and coagulation using a nitroxide radical-containing polymer with reactive oxygen species scavenging activity

Yoshitomi Toru,Yamaguchi Yu,Kikuchi Akihiko,Nagasaki Yukio,吉冨徹,長崎幸夫
Acta Biomaterialia 8(3), 1323-1329, 2012-03
… Both platelet and leukocyte adhesion to the beads were suppressed with increasing TEMPO incorporation in the polymer. …
NAID 120003988714

Chemokines in tumor development and progression

Mukaida Naofumi,Baba Tomohisa
Experimental Cell Research 318(2), 95-102, 2012-01-15
… Chemokines were originally identified as mediators of the inflammatory process and regulators of leukocyte trafficking. … Subsequent studies revealed their essential roles in leukocyte physiology and pathology. …
NAID 80022173851

4)免疫学的異常による流産原因の解明(シンポジウム1「流産の原因と対策」,第63回日本産科婦人科学会・学術講演会)

中島彰俊
日本産科婦人科學會雜誌 63(12), 2185-2197, 2011-12-01
… For example, villous trophoblasts do not express classical major histocompatibility complex (MHC) class I and class II molecules in humans, and human extravillous trophoblasts express only MHC-class I molecules such as human histocompatibility leukocyte antigen (HLA)-C, HLA-E, and HLA-G, which are specific ligands for uterine natural killer (NK) cells. …
NAID 110008799037

Related Pictures

★リンクテーブル★

リンク元	「100Cases 33」「白血球」「leukocytic」「白血球細胞」
拡張検索	「fecal leukocytes」「leukocyte migration-inhibitory factor」

「100Cases 33」

White blood cell
	A scanning electron microscope image of normal circulating human blood. In addition to the irregularly shaped leukocytes, both red blood cells and many small disc-shaped platelets are visible.
Details
Latin	leucocytus
Identifiers
Code	TH H2.00.04.1.02001
	Anatomical terminology

　　[★]

☆case33　頭痛と混乱

■glossary

accompany

vt.

(人)と同行する、(人)に随行する。(もの)に付随する。～と同時に起こる。～に加える(添える、同封する)(with)

slurred n. 不明瞭

強直間代痙攣 tonic-clonic convulsion

　意識消失とともに全身の随意筋に強直痙攣が生じ(強直痙攣期tonic convulsion)、次いで全身の筋の強直と弛緩とが律動的に繰り返される時期(間代痙攣期clonic convulsion)を経て、発作後もうろう状態を呈する一連の発作。

■症例

28歳、女性　黒人　南アフリカ　手術室看護師　ロンドン住在

主訴：頭痛と混乱

現病歴：過去3週間で頭痛が続いており、ひどくなってきた。現在も頭痛が持続しており、頭全体が痛い。友人曰く「過去六ヶ月で体重が10kg減っていて、最近、混乱してきたようだ」。発話は不明瞭。救急室にいる間に強直間代痙攣を起こした。

・診察 examination

やせている。55kg。38.5℃。口腔カンジダ症(oral candidiasis)。リンパ節腫脹無し。心血管、呼吸器系、消化器系正常。痙攣前における神経検査では時間、場所、人の見当識無し。神経局所症状無し(no focal neurological sign)。眼底両側に乳頭浮腫有り。

・検査 investigation

血算：白血球増多

血液生化学：ナトリウム低下

CT：供覧

■キーワード＆着目するポイント

・口腔カンジダ症(oral candidiasis)

・頭痛、精神症状、強直間代痙攣

・眼底両側に乳頭浮腫

・CT 所見

・低ナトリウム血症は二次的なもの

■アプローチ

・口腔カンジダ症(oral candidiasis)　→　細胞免疫低下状態(DM、免疫抑制、AIDSなど) or 常在細菌叢の攪乱(長期の抗菌薬の使用)

　・The occurrence of thrush in a young, otherwise healthy-appearing person should prompt an investigation for underlying HIV infection.(HIM.1254)

　・More commonly, thrush is seen as a nonspecific manifestation of severe debilitating illness.(HIM.1254)

・精神症状、強直間代痙攣　→　一次的、あるいは二次的な脳の疾患がありそう

・頭痛　→　漠然としていて絞れないが、他の症状からして機能性頭痛ではなく症候性頭痛っぽい。

・眼底両側に乳頭浮腫　→　脳圧亢進の徴候　→　原因は・・・脳腫瘍、ことにテント下腫瘍と側頭葉の腫瘍、クモ膜下出血、脳水腫など、そのほか、眼窩内病変、低眼圧などの局所的要因、悪性高血圧、血液疾患、大量出血、肺気腫などの全身的要因 (vindicate本のp342も参考になる)

　・頭痛と脳圧亢進　→　頭蓋内圧占拠性病変、脳炎(IMD.274)

・CT 所見　→　ringformの病変、脳浮腫、脳圧亢進

・低ナトリウム血症　→　脳ヘルニアに続発して起こることがあるらしい。実際には下垂体にトキソプラズマによる病変が形成されることにより起こりうる。

・そのほか出身地、体重減少もHIVを疑わせる点

パターン認識でHIV + 精神症状 + てんかん発作(強直間代痙攣) + 脳圧亢進 + CT 所見 = 一番ありそうなのはToxoplasma gondiiによるトキソプラズマ脳症 cerebral toxoplasosis (トキソプラズマ脳炎 toxoplasmic encephalitis)

■Toxoplasma gondii

　原虫　胞子原虫類

(感染予防学 080521のプリント、CASES p,92、HIM p.1305-)

・疫学：西洋では30-80%の成人がトキソプラズマの感染の既往がある・・・うぇ(CASES)。日本では10%前後(Wikipedia)。

・生活環

　・終宿主：ネコ：ネコの小腸上皮細胞で有性・無性生殖　糞便にオーシストの排泄

　・中間宿主：ヒト.ブタを含むほ乳類と鳥類：無性生殖で増殖、シストの形成

　　　急性期の増殖盛んな急増虫体 tachyzoiteとシスト内の緩増虫体 bradyzoite

・病原、病因 phathogenesis

　・緩増虫体(bradyzoite)、接合子嚢(oocyst)

・感染経路

　1. オーシストの経口摂取

　2. 中間宿主の生肉中のシストの経口摂取

　3. 初感染妊婦からの経胎盤感染。既感染なら胎盤感染しないらしい(HIM.1306)

　(4)移植臓器、輸血。確率は低い(at low rate)(HIM.1306)

・病態

　1. 先天性トキソプラズマ症　congenital toxoplasmosis

　　　①網脈絡膜炎、 ②水頭症、 ③脳内石灰化、 ④精神・運動障害

　2. 後天性トキソプラズマ症　acquired toxoplasmosis

　　(1) 健常者

　　　・多くは不顕性感染。発熱、リンパ節腫脹、皮疹(rash)

　　　・(少数例)筋肉痛、暈疼痛、腹痛、斑状丘疹状皮疹(maculopapular rash)、脳脊髄炎、混乱(HIM.1308)

　　　・(まれ)肺炎、心筋炎、脳症、心膜炎、多発筋炎

　　　・網膜、脈絡叢に瘢痕や、脳に小さい炎症性の病変を残すことあり(CASES)。

　　　・急性感染の症状は数週間で消失　筋肉や中枢神経系に緩増虫体が残存

　　(2)HIV 感染者、臓器移植例、がん化学療法例

　　　シスト内緩増虫体→急増虫体→播種性の多臓器感染

　　　AIDSでは、トキソプラズマ性脳炎が指標疾患 AIDS-defineing illness(CASES)

・治療

　(日本)アセチルスピラマイシン、ファンシダール(感染予防学 080521)

■トキソプラズマ脳炎 toxoplasmic encephalitis、トキソプラズマ脳症 cerebral toxoplasosis

・症状

　発熱、頭痛、混乱ｍ、痙攣、認知の障害、局所神経徴候(不全片麻痺、歯垢、脳神経損傷、視野欠損、感覚喪失)(CASES)

・画像検査

　(CT,MRI)多発性、両側性、ring-enhancing lesion、特に灰白質-白質境界、大脳基底核、脳幹、小脳が冒されやすい(CASES)

・鑑別診断(臨床症状・画像診断の所見で)

　リンパ腫、結核、転移性脳腫瘍(CASES)

・病歴と画像所見からの鑑別診断

　リンパ腫、結核、転移性腫瘍

？

このCTがcerebral toxoplasmosisに特徴的かは不明

□最後に残る疑問

　AIDSでWBC(leukocyte)の数はどうなるんだろう？？？AIDSの初診患者ではWBCが低い人が多いらしいし()、HIVはCD4+ T cellとmacrophageに感染して殺すから、これによってB cellは減るだろうし、CD8+ T cellも若干減少するだろうからWBCは減るんじゃないか？！好中球はAIDSとは関係ない？好中球は他の感染症に反応性に増加している？ちなみに、好酸球は寄生虫(原虫)の感染のために増える傾向にあるらしい(HIMのどこか)。

葉酸拮抗剤である。

サルファ剤と併用され、抗トキソプラズマ薬、抗ニューモシチス・カリニ薬として相乗的に働く。

ST 合剤

SMX-TMP

スルファメトキサゾール・トリメトプリム合剤 sulfamethoxazole and trimethoprim mixture

□AIDSの定義(http://en.wikipedia.org/wiki/CDC_Classification_System_for_HIV_Infection_in_Adults_and_Adolescents)

According to the US CDC definition, one has AIDS if he/she is infected with HIV and present with one of the following:

A CD4+ T-cell count below 200 cells/μl (or a CD4+ T-cell percentage of total lymphocytes of less than 14%).

or he/she has one of the following defining illnesses:

01. Candidiasis of bronchi, trachea, or lungs
02. Candidiasis esophageal
03. Cervical cancer (invasive)
04. Coccidioidomycosis, disseminated or extrapulmonary
05. Cryptococcosis, extrapulmonary
06. Cryptosporidiosis, chronic intestinal for longer than 1 month
07. Cytomegalovirus disease (other than liver, spleen or lymph nodes)
08. Encephalopathy (HIV-related)
09. Herpes simplex: chronic ulcer(s) (for more than 1 month); or bronchitis, pneumonitis, or esophagitis
10. Histoplasmosis, disseminated or extrapulmonary
11. Isosporiasis, chronic intestinal (for more than 1 month)
12. Kaposi's sarcoma
13. Lymphoma Burkitt's, immunoblastic or primary brain
14. Mycobacterium avium complex
15. Mycobacterium, other species, disseminated or extrapulmonary
16. Pneumocystis carinii pneumonia
17. Pneumonia (recurrent)
18. Progressive multifocal leukoencephalopathy
19. Salmonella septicemia (recurrent)
20. Toxoplasmosis of the brain
21. Tuberculosis
22. Wasting syndrome due to HIV

People who are not infected with HIV may also develop these conditions; this does not mean they have AIDS. However, when an individual presents laboratory evidence against HIV infection, a diagnosis of AIDS is ruled out unless the patient has not:

undergone high-dose corticoid therapy or other immunosuppressive/cytotoxic therapy in the three months before the onset of the indicator disease
OR been diagnosed with Hodgkin's disease, non-Hodgkin's lymphoma, lymphocytic leukemia, multiple myeloma, or any cancer of lymphoreticular or histiocytic tissue, or angioimmunoblastic lymphoadenopathy
OR a genetic immunodeficiency syndrome atypical of HIV infection, such as one involving hypogamma globulinemia

AND

the individual has had Pneumocystis carinii pneumonia
OR one of the above defining illnesses AND a CD4+ T-cell count below 200 cells/μl (or a CD4+ T-cell percentage of total lymphocytes of less than 14%).

□AIDSのステージング

Revised World Health Organization (WHO) Clinical Staging of HIV/AIDS For Adults and Adolescents (2005)

http://en.wikipedia.org/wiki/WHO_Disease_Staging_System_for_HIV_Infection_and_Disease_in_Adults_and_Adolescents

■参考文献

HIM = Harrison's Principles of Internal Medicine 17th Edition

CASES = 100 Cases in Clinical Medicine Second edition

IMD = 内科診断学第2版

「白血球」

　　[★]

英: leukocyte, leucocyte (Z), white blood cell (Z), WBC, white corpuscle, white cell
関: 赤血球、血球、血液

白血球

顆粒球

基準値

4000-9000 (/μl)　(2007前期解剖学授業プリント)

異常値の出るメカニズム第5版

5000- 8400 (/μl) (健常者の2/3)
4500-11000 (/μl) (95%範囲)

年齢との関連

新生児期>幼児期>成人期(20歳までに成人値)
妊婦でも増加(妊娠#妊娠による変化)

生理的な変動

精神的ストレス↑　　→　交感神経の刺激により好中球の血管壁遊離が促進されるため
午前↓、午後↑

基準値

			07解	異メ	流マ		HIM.A-1
顆粒球	好中球	桿状核球	40～70	44～66	40～60	4～14	0～5
		分葉核球				43～59	40～70
	好酸球		2～4	0～ 4	2～4		0～6
	好塩基球		0～2	0～0.5	0～2		0～2
無顆粒球	リンパ球		25～40	30～38	26～40		20～50
	単球		3～6	0～ 5	3～6		4～8

07解: 2007前期解剖学授業プリント
異メ: 異常値の出るメカニズム第5版 p.91
流マ: 流れが分かる実践検査マニュアル上巻 p.10

血管外滲出 extravasation (SMB.37 BPT.37)

(margination)

1. 赤血球は軽く早く流れるので血管の中央をながれ、白血球は血管のへりを流れている

(rolling)

2. IL-1, TNFで血管内皮細胞が活性化し、血管内腔にE-selectinを発現する
3. P-selectinはヒスタミンやトロンビンの働きにより、血管内腔に発現する
4. 白血球と血管内皮細胞の接着分子で接着することで、白血球がrollingを始める
3. 次第にselectinによる接着はdown regulateされる

(adheresion & arrested)

4. 炎症部位から出されたケモカインが血管内皮細胞の表面ののペプチドグリカンに結合し、白血球に提示される
5. 白血球表面のインテグリンが活性化し、血管内皮細胞のICAM-1, VCAM-1と強く結合する

(transmigration)

6. 白血球と血管内皮細胞に発現しているPECAM-1(CD31)がお互い接着し、白血球が血管内皮細胞の間隙を通って細胞外マトリックスに入る

血管内皮細胞		白血球
Rolling
E-selectin	－	糖鎖(SLe^x)
P-selectin	－	糖鎖
糖鎖(GlyCAM-1)(=CD34)	－	L-selectin
Adhestion
ICAM-1	－	LFA-1 integlin(CD11a/CD18), Mac-1 integlin(CD11b/CD18)
VCAM-1	－	VLA-1 integlin
transmigration
PECAM-1(CD31)	－	PECAM-1(CD31)