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| ==Differentiating Wiskott-Aldrich Syndrome From Other Disorders of Humoral Imuunodeficiency== | | ==pic== |
| Wiskott-Aldrich Syndrome should be differentiated from other disorders leading to [[hypogammaglobulinemia]] and defects of [[humoral immunity]]. The following conditions may be considered as differentials:
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| {|
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| ! align="center" style="background:#4479BA; color: #FFFFFF;" + |Disorder
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| ! align="center" style="background:#4479BA; color: #FFFFFF;" + |Mechanism
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| ! align="center" style="background:#4479BA; color: #FFFFFF;" + |Characteristic Features
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| ! align="center" style="background:#4479BA; color: #FFFFFF;" + |Clinical Presentation
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| ! align="center" style="background:#4479BA; color: #FFFFFF;" + |Laboratory Findings
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| |-
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| ! align="center" style="background:#DCDCDC;" + |[[Wiskott-Aldrich syndrome|Wiskott-Aldrich Syndrome]]
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| | align="left" style="background:#F5F5F5;" + |
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| * [[Mutation]] in [[WAS]] [[gene]]
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| * [[T cells]] unable to reorganize [[actin]] [[microfilaments]] ([[microfilament]] defect)
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| | align="left" style="background:#F5F5F5;" + |
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| * [[X-linked recessive]] pattern of inheritance
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| * Increased risk of [[autoimmune disease]] and [[malignancy]]
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| | align="left" style="background:#F5F5F5;" + |
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| * [[Thrombocytopenic purpura]]
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| * [[Eczema]]
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| * Recurrent [[infections]]
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| | align="left" style="background:#F5F5F5;" + |
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| * Decreased to normal [[Immunoglobulin G|IgG]] and [[Immunoglobulin M|IgM]]
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| * Increased [[Immunoglobulin E|IgE]] and [[IgA]]
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| * Fewer and smaller [[platelets]]
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| |-
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| ! align="center" style="background:#DCDCDC;" + |[[X-linked agammaglobulinemia|X-Linked (Bruton) Agammaglobulinemia]]
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| | align="left" style="background:#F5F5F5;" + |
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| * Defect in [[tyrosine kinase]] [[gene]] ([[Bruton's tyrosine kinase|BTK]])
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| * [[B cells]] fail to mature
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| | align="left" style="background:#F5F5F5;" + |
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| * [[X-linked recessive]] pattern of inheritance
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| * Increased [[prevalence]] in [[males]]
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| | align="left" style="background:#F5F5F5;" + |
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| * Recurrent [[bacterial]] and [[enteroviral]] [[infections]] after 6 months of age
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| * Pre-disposition to development of [[infections]] by [[encapsulated organisms]]
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| * Pre-disposition to development of Giardia infections
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| * Absent lymph nodes and tonsils
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| | align="left" style="background:#F5F5F5;" + |
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| * Normal [[CD19|CD19+ B cell]] count
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| * Decreased pro-[[B cells]]
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| * Increased pre-[[B cells]]
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| * Decreased [[immunoglobulins]] of all classes
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| |-
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| ! align="center" style="background:#DCDCDC;" + |[[IgA deficiency|Selective IgA Deficiency]]
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| | align="left" style="background:#F5F5F5;" + |
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| * [[Stem cell]] defect (Transferrable with [[Bone marrow transplant|marrow transplant]])
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| * Lack of [[Interleukin 4|IL-4]], [[Interleukin 6|IL-6]], [[Interleukin 7|IL-7]], [[Interleukin 10|IL-10]], [[TGF beta|TGF-β]], and [[Interleukin 21|IL-21]]
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| * [[Mutations]] in [[transmembrane]] activator and calcium-modulator and [[cyclophilin]] ligand interactor ([[TACI]], [[TNFRSF13B]])
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| | align="left" style="background:#F5F5F5;" + |
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| * Most common primary [[immune deficiency]]
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| | align="left" style="background:#F5F5F5;" + |
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| * Majority of the cases are [[asymptomatic]]
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| * Respiratory and [[gastrointestinal]] infections ([[mucosal]] infections)
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| * Associated with [[autoimmune diseases]]
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| * [[Atopy]]
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| * [[Anaphylaxis]] to [[IgA]] containing products
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| | align="left" style="background:#F5F5F5;" + |
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| * Serum [[IgA]] < 7 mg/dl
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| * Normal [[IgG]] and [[IgM]] levels
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| |-
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| ! align="center" style="background:#DCDCDC;" + |[[Common variable immunodeficiency|Common Variable Immunodeficiency]]
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| | align="left" style="background:#F5F5F5;" + |
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| * Defective [[B cell]] differentiation
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| | align="left" style="background:#F5F5F5;" + |
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| * May be acquired in 20-30 years of age
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| | align="left" style="background:#F5F5F5;" + |
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| * May present with other [[autoimmune diseases]]
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| * Associated with [[bronchiectasis]]
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| * Associated with [[lymphoma]]
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| * Associated with sinopulmonary infections ([[Bacterial]], [[enteroviral]] and [[parasitic]] such as [[Giardia]])
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| | align="left" style="background:#F5F5F5;" + |
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| * Decreased [[plasma cells]]
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| * Decreased [[immunoglobulins]]
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| |-
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| ! align="center" style="background:#DCDCDC;" + |[[Job's syndrome|Autosomal dominant hype IgE syndrome (Job's Syndrome)]]
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| | align="left" style="background:#F5F5F5;" + |
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| * Defieciency of [[T helper 17 cell|Th17 cells]] due to [[STAT3]] [[mutation]]
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| * Impaired [[neutrophils]] to sites of [[infection]]
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| | align="left" style="background:#F5F5F5;" + |
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| * Distinctive coarse facies
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| * Cold (non-inflammatory) Staphylococcal abscesses
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| * Retained primary teeth
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| * Eczema
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| | align="left" style="background:#F5F5F5;" + |
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| | align="left" style="background:#F5F5F5;" + |
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| * Increased levels of [[IgE]]
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| * Decreased levels of [[interferon gamma]] (IFN-gamma)
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| |-
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| ! align="center" style="background:#DCDCDC;" + |[[Severe combined immunodeficiency|Severe combined immunodeficiency (SCID)]]
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| | align="left" style="background:#F5F5F5;" + |
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| * Defective [[Interleukin-2 receptor|interleukin-2 receptor gamma chain]]
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| * [[Adenosine deaminase]] deficiency
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| * Reg 1 and Reg 2 [[nonsense mutations]]
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| | align="left" style="background:#F5F5F5;" + |
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| * [[Interleukin 20 receptor, alpha subunit|IL-2R]] disease is [[X-linked]]
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| * [[Adenosine deaminase|ADA]] deficiency and reg mutations are typically [[autosomal recessive]]
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| | align="left" style="background:#F5F5F5;" + |
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| * [[Failure to thrive]]
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| * [[Chronic diarrhea]]
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| * [[Thrush]]
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| * Recurrent [[bacterial]], [[viral]] and [[protozoal]] infections
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| * Treatment is [[bone marrow]] [[transplant]]
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| | align="left" style="background:#F5F5F5;" + |
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| * Decreased [[T cell]] receptor excision circles (TRECs)
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| * Abscence of [[thymic]] shadow on [[Chest X-ray|chest X-Ray]]
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| * Absent [[germinal centers]] of [[lymph node biopsy]]
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| * Absent [[T cells]] on [[flow cytometry]]
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| |-
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| ! align="center" style="background:#DCDCDC;" + |[[Ataxia telangiectasia|Ataxia Telangiectasia]]
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| | align="left" style="background:#F5F5F5;" + |
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| * Defect in [[ATM|ATM gene]]
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| * [[DNA]] double stranded breaks leading to [[cell cycle]] arrest
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| | align="left" style="background:#F5F5F5;" + |
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| * Hypersensitivity to [[X-Ray|X-Rays]]
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| | align="left" style="background:#F5F5F5;" + |
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| * Triad of:
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| ** [[Ataxia]]
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| ** Spider [[Angioma|angiomas]] (Nests of distended [[capillaries]])
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| ** [[IgA deficiency]]
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| | align="left" style="background:#F5F5F5;" + |
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| * Increased [[alpha fetoprotein]] ([[Alpha-fetoprotein|AFP]])
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| * Decreased [[IgA]], [[IgG]] and [[IgE]]
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| * [[Lymphopenia]]
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| * [[Cerebellar]] atrophy
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| |-
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| ! align="center" style="background:#DCDCDC;" + |[[Hyper IgM Syndrome Type 1|Hyper IgM Syndrome]]
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| | align="left" style="background:#F5F5F5;" + |
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| * Defective [[CD40L]] ([[CD40L|CD40 ligand]]) on [[T helper cell|Th cells]] leading to [[class switching]] defect
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| | align="left" style="background:#F5F5F5;" + |
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| * [[X-linked recessive]] pattern of inheritance
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| | align="left" style="background:#F5F5F5;" + |
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| * Severe pyogenic infections in early life
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| * Opportunistic infection with:
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| ** [[Pneumocystis jiroveci]]
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| ** [[Cryptosporidium]]
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| ** [[Cytomegalovirus]] ([[Cytomegalovirus infection|CMV]])
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| | align="left" style="background:#F5F5F5;" + |
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| * Increased [[Immunoglobulin M|IgM]]
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| * Decreased [[Immunoglobulin G|IgG]], [[IgA]] and [[Immunoglobulin E|IgE]]
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| * No [[germinal centers]]
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| |}
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| :*Malignancy: can cause the reduction in the immunoglobulin production.
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| *Viral infections: such as Epstein-Barr virus, HIV, cytomegalovirus are other causes of hypogammaglobulinemia..
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| *Side effect of certain medications: Some drugs include systemic glucocorticoids, phenytoin, and carbamazepine, have been associated with IgG deficiency.
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| *Other causes of primary humoral immunodeficiencies.
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| *Smoking: may cause IgG2 subclass deficiency.
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| *Protein-losing conditions: enteropathies, nephrotic syndrome, burns, and other traumas may cause abnormal loss of immunoglobulins.
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| {| | | {| |
| |[[image:LowKECG.png|thumb|700px|center|An ECG in a person with a potassium level of 1.1 showing the classical ECG changes of ST segment depression, inverted T waves, large U waves, and a slightly prolonged PR interval. By James Heilman, MD - Own work, CC BY-SA 3.0]] | | |[[image:LowKECG.png|thumb|700px|center|An ECG in a person with a potassium level of 1.1 showing the classical ECG changes of ST segment depression, inverted T waves, large U waves, and a slightly prolonged PR interval. By James Heilman, MD - Own work, CC BY-SA 3.0]] |
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| <br style="clear:left" /> | | <br style="clear:left" /> |
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| [[image:LowKECG.png|thumb|700px|center|An ECG in a person with a potassium level of 1.1 showing the classical ECG changes of ST segment depression, inverted T waves, large U waves, and a slightly prolonged PR interval. By James Heilman, MD - Own work, CC BY-SA 3.0]] | | [[image:LowKECG.png|thumb|700px|right|An ECG in a person with a potassium level of 1.1 showing the classical ECG changes of ST segment depression, inverted T waves, large U waves, and a slightly prolonged PR interval. By James Heilman, MD - Own work, CC BY-SA 3.0]] |
| <br style="clear:left" /> | | <br style="clear:left" /> |
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| | align="left" style="background:#F5F5F5;" + | | | | align="left" style="background:#F5F5F5;" + | |
| *[[Lung]] | | *[[Lung]] |
| | align="left" style="background:#F5F5F5;" + | | | | align="center" style="background:#F5F5F5;" + | |
| *[[Lung]] | | *[[Lung]] |
| |} | | |} |
| <br>
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| <references />
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