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Deep Learning Technology: Sebastian Arnold, Betty van Aken, Paul Grundmann, Felix A. Gers and Alexander Löser. Learning Contextualized Document Representations for Healthcare Answer Retrieval. The Web Conference 2020 (WWW'20)
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Neutrophilia is an increase in the absolute neutrophil count in the peripheral circulation. Normal blood values vary by age. 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.
Primary causes
- 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
Secondary causes
- Infection
- Chronic inflammation – especially juvenile rheumatoid arthritis, rheumatoid arthritis, Still's disease, 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
Monocytosis is the state of excess monocytes in the peripheral blood. It may be indicative of various disease states.
Examples of processes that can increase a monocyte count include:
- chronic inflammation
- stress response
- Cushing's syndrome (hyperadrenocorticism)
- immune-mediated disease
- granulomatous disease
- atherosclerosis
- necrosis
- red blood cell regeneration
- viral fever
- sarcoidosis
A high count of CD14+CD16++ monocytes is found in severe infection (sepsis)
In the field of atherosclerosis high numbers of the CD14++CD16+ intermediate monocytes were shown to be predictive of cardiovascular events in at risk populations.
Neutropenia can be acquired or intrinsic. A decrease in levels of neutrophils on lab tests is due to either decreased production of neutrophils or increased removal from the blood. 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, Chédiak–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. One severe consequence of neutropenia is that it can increase the risk of infection.
Granulocytopenia is an abnormally low concentration of granulocytes in the blood. This condition reduces the body's resistance to many infections. Closely related terms include agranulocytosis (etymologically, "no granulocytes at all"; clinically, granulocyte levels less than 5% of normal) and neutropenia (deficiency of neutrophil granulocytes). Granulocytes live only one to two days in circulation (four days in spleen or other tissue), so transfusion of granulocytes as a therapeutic strategy would confer a very short-lasting benefit. In addition, there are many complications associated with such a procedure.
There is usually a granulocyte chemotactic defect in individuals suffering from insulin-dependent diabetes mellitus.
Small image of an infected area of the body due to a reaction with an implant
Monocytopenia is a form of leukopenia associated with a deficiency of monocytes.
A very low count of these cells is found after therapy with immuno-suppressive glucocorticoids.
Also, non-classical slan+ monocytes are strongly reduced in patients with hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS), a neurologic disease associated
with mutations in the macrophage colony-stimulating factor receptor gene.
In some cancers, such as melanoma and colorectal cancer, lymphocytes can migrate into and attack the tumor. This can sometimes lead to regression of the primary tumor.
Granulocytes are a category of white blood cells characterized by the presence of granules in their cytoplasm. They are also called polymorphonuclear leukocytes (PMN, PML, or PMNL) because of the varying shapes of the nucleus, which is usually lobed into three segments. This distinguishes them from the mononuclear agranulocytes. In common parlance, the term "polymorphonuclear leukocyte" often refers specifically to "neutrophil granulocytes", the most abundant of the granulocytes; the other types (eosinophils, basophils, and mast cells) have lower numbers. Granulocytes are produced via granulopoiesis in the bone marrow.
A lymphocyte is one of the subtypes of white blood cell in a vertebrate's immune system. Lymphocytes include natural killer cells (Phagocytes) (which function in cell-mediated, cytotoxic innate immunity), T cells (for cell-mediated, cytotoxic adaptive immunity), and B cells (for humoral, antibody-driven adaptive immunity). They are the main type of cell found in lymph, which prompted the name "lymphocyte".
Neutrophils (also known as neutrocytes) are the most abundant type of granulocytes and the most abundant (40% to 70%) type of white blood cells in most mammals. They form an essential part of the innate immune system. Their functions vary in different animals.
They are formed from stem cells in the bone marrow. They are short-lived and highly motile, or mobile, as they can enter parts of tissue where other cells/molecules cannot. Neutrophils may be subdivided into segmented neutrophils and banded neutrophils (or bands). They form part of the polymorphonuclear cells family (PMNs) together with basophils and eosinophils.
The name "neutrophil" derives from staining characteristics on hematoxylin and eosin (H&E) histological or cytological preparations. Whereas basophilic white blood cells stain dark blue and eosinophilic white blood cells stain bright red, neutrophils stain a neutral pink. Normally, neutrophils contain a nucleus divided into 2–5 lobes.
Neutrophils are a type of phagocyte and are normally found in the bloodstream. During the beginning (acute) phase of inflammation, particularly as a result of bacterial infection, environmental exposure, and some cancers, neutrophils are one of the first-responders of inflammatory cells to migrate towards the site of inflammation. They migrate through the blood vessels, then through tissue, following chemical signals such as Interleukin-8 (IL-8), C5a, fMLP, Leukotriene B4 and HO in a process called chemotaxis. They are the predominant cells in pus, accounting for its whitish/yellowish appearance.
Neutrophils are recruited to the site of injury within minutes following trauma, and are the hallmark of acute inflammation; however, due to some pathogens being indigestible, they can be unable to resolve certain infections without the assistance of other types of immune cells.
Neutrophils are the primary white blood cells that respond to a bacterial infection, so the most common cause of neutrophilia is a bacterial infection, especially pyogenic infections.
Neutrophils are also increased in any acute inflammation, so will be raised after a heart attack, other infarct or burns.
Some drugs, such as prednisone, have the same effect as cortisol and adrenaline (epinephrine), causing marginated neutrophils to enter the blood stream. Nervousness will very slightly raise the neutrophil count because of this effect.
A neutrophilia might also be the result of a malignancy. Chronic myelogenous leukemia (CML or chronic myeloid leukaemia) is a disease where the blood cells proliferate out of control. These cells may be neutrophils. Neutrophilia can also be caused by appendicitis and splenectomy.
Primary neutrophilia can additionally be a result of Leukocyte adhesion deficiency.
Morning pseudoneutropenia is a transient reduction in the measured neutrophil count from peripheral samples. This is noticed in some patients who are taking antipsychotic medication. Morning pseudoneutropenia is thought to be due to diurnal variation in the amount of circulating white blood cells and changes in the levels of hematopoietic cytokines and granulocyte colony stimulating factor (GCSF). Antipsychotics may amplify the natural variation in these hematopoietic factors.
Neutropenia is a hematological disorder characterized by an abnormally low number of neutrophils in the blood. Neutrophils usually make up 50-70% of circulating white blood cells and serve as the primary defense against infections. There is some variability in the neutrophil counts depending upon when the sample is taken, where the blood sample is taken from, and the system used by the medical lab for measuring the blood cells, but any significant reduction in function or number below the appropriate range may predispose individuals to infections.
Case reports of such incidences are reported with Clozapine and Risperidone and Aripiprazole.
These case reports suggest that the observed cases of the morning pseudoneutropenia did not proceed to become agranulocytosis which is a significant and dangerous side effect of some of antipsychotics. Hence it was suggested that although the morning neutrophil count may appear low, if the antipsychotic medication were considered efficaceous then white cell counts may be repeated in the afternoon prior to making a decision based only on the morning counts.
A foreign-body giant cell is a collection of fused macrophages (giant cell) which are generated in response to the presence of a large foreign body. This is particularly evident with implants that cause the body chronic inflammation and foreign body response.
This reaction to the implant causes damages to the infected area, leaving the exterior surface with scars.
The nuclei are arranged in a disorganized manner. The nuclei in this cell are centrally placed and overlap each other. This is in contrast to a Langhans giant cell, where the nuclei are arranged on the border.
Foreign body cells can detect and eliminate
bacteria caught within the body, by sensing the unique sugar coating that are
on the invading prokaryotes. These macrophage cells are one of a few
phagocytic cells, but not the first to come to an injury site, and tend to
linger from anytime between days to weeks. There has been some research done on other variations of
giant calls with different functions.
Neutrophils display highly directional amoeboid motility in infected footpad and phalanges. Intravital imaging was performed in the footpad path of LysM-eGFP mice 20 minutes after infection with "Listeria monocytogenes".
A "left shift" refers to the presence of increased proportions of younger, less well differentiated neutrophils and neutrophil-precursor cells in the blood. This generally reflects early or premature release of myeloid cells from the bone marrow, the site where neutrophils are generated. A severe neutrophilia with left shift is referred to as a leukemoid reaction. The leukocyte alkaline phosphatase (LAP) score, which refers to the amount of alkaline phosphatase per neutrophil, will increase. In a severe infection, toxic granulation changes happen to the neutrophils.
This can resemble Pelger-Huet anomaly.
Estimation of the frequency of SGD is difficult, as it is an extremely rare disease with few cases reported in literature. The condition was first reported in 1980, and since only a handful more cases have been published.
In cardiovascular disease, increased white blood cell counts have been shown to indicate a worse prognosis.
A 2009 study reported results from 36 children who had received a stem cell transplant. At the time of follow-up (median time 62 months), 75% of the children were still alive.
Neutrophil-specific granule deficiency (SGD, previously known as lactoferrin deficiency) is a rare congenital immunodeficiency characterized by an increased risk for pyogenic infections due to defective production of specific granules and gelatinase granules in patient neutrophils.
It is believed that cytokines (including IL-1 and TNF) accelerate the release of cells from the postmitotic reserve pool in the bone marrow, leading to an increased number of immature cells.
An increase in eosinophil granulocyte is known as eosinophilia.
Granulocytosis can be a feature of a number of diseases:
- Infection, especially bacterial
- Malignancy, most notably leukemia (it is the main feature of chronic myelogenous leukemia, CML)
- Autoimmune disease
LAD is a rare disease, with an estimated prevalence of one in 100,000 births, with no described racial or ethnic predilection. The most common type is LAD1.
As noted above, a leukemoid reaction is typically a response to an underlying medical issue. Causes of leukemoid reactions include:
- Severe hemorrhage (retroperitoneal hemorrhage)
- Drugs
- Use of sulfa drugs
- Use of dapsone
- Use of glucocorticoids
- Use of G-CSF or related growth factors
- All-trans retinoic acid (ATRA)
- Ethylene glycol intoxication
- Infections
- Clostridium difficile
- Tuberculosis
- Pertussis
- Infectious mononucleosis (lymphocyte predominant)
- Visceral larva migrans (eosinophil predominant)
- Asplenia
- Diabetic ketoacidosis
- Organ necrosis
- Hepatic necrosis
- Ischemic colitis
- As a feature of trisomy 21 in infancy (incidence of ~10%)
- As a paraneoplastic phenomenon (rare)
In many cases, MHA requires no treatment. However, in extreme cases, blood platelet transfusions may be necessary
Although it may occur in the absence of other known disease, SS is often associated with hematologic disease (including leukemia), and immunologic disease (rheumatoid arthritis, inflammatory bowel disease, Behçet's syndrome).
A genetic association has been suggested, but no specific genetic link has been identified.