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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.
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.
Monocytes are a type of "leukocyte", or white blood cell. They are the largest type of leukocyte and can differentiate into macrophages and myeloid lineage dendritic cells. As a part of the vertebrate innate immune system monocytes also influence the process of adaptive immunity. There are at least three subclasses of monocytes in human blood based on their phenotypic receptors.
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 white blood cells are produced and derived from multipotent cells in the bone marrow known as hematopoietic stem cells. Leukocytes are found throughout the body, including the blood and lymphatic system.
All white blood cells have nuclei, which distinguishes them from the other blood cells, the anucleated red blood cells (RBCs) and platelets. Types of white blood cells can be classified in standard ways. Two pairs of broadest categories classify them either by structure (granulocytes or agranulocytes) or by cell division lineage (myeloid cells or lymphoid cells). These broadest categories can be further divided into the five main types: neutrophils, eosinophils (acidophilus), basophils, lymphocytes, and monocytes. These types are distinguished by their physical and functional characteristics. Monocytes and neutrophils are phagocytic. Further subtypes can be classified; for example, among lymphocytes, there are B cells, T cells, and NK cells.
The number of leukocytes in the blood is often an indicator of disease, and thus the WBC count is an important subset of the complete blood count. The normal white cell count is usually between 4 × 10/L and 11 × 10/L. In the US this is usually expressed as 4,000 to 11,000 white blood cells per microliter of blood. They make up approximately 1% of the total blood volume in a healthy adult, making them substantially less numerous than the RBCs at 40% to 45%. However, this 1% of the blood makes a large difference to health, because immunity depends on it. An increase in the number of leukocytes over the upper limits is called leukocytosis. It is normal when it is part of healthy immune responses, which happen frequently. It is occasionally abnormal, when it is neoplastic or autoimmune in origin. A decrease below the lower limit is called leukopenia. This indicates a weakened immune system.
There are four types of granulocytes:
- Basophils
- Eosinophils
- Neutrophils
- Mast cells
Their names are derived from their staining characteristics; for example, the most abundant granulocyte is the neutrophil granulocyte, which has neutrally staining cytoplasmic granules.
A histiocyte is an animal cell that is part of the mononuclear phagocyte system (also known as the reticuloendothelial system or lymphoreticular system). The mononuclear phagocytic system is part of the organism's immune system. The histiocyte is a tissue macrophage or a dendritic cell (histio, diminutive of histo, meaning "tissue", and cyte, meaning "cell").
Monocytes are amoeboid in appearance, and have agranulated cytoplasm. Containing unilobar nuclei, these cells are one of the types of mononuclear leukocytes which shelter azurophil granules. The archetypal geometry of the monocyte nucleus is ellipsoidal; metaphorically bean-shaped or kidney-shaped, although the most significant distinction is that the nuclear envelope should not be hyperbolically furcated into lobes. Contrast to this classification occurs in polymorphonuclear leukocytes. Monocytes compose 2% to 10% of all leukocytes in the human body and serve multiple roles in immune function. Such roles include: replenishing resident macrophages under normal conditions; migration within approximately 8–12 hours in response to inflammation signals from sites of infection in the tissues; and differentiation into macrophages or dendritic cells to effect an immune response. In an adult human, half of the monocytes are stored in the spleen. These change into macrophages after entering into appropriate tissue spaces, and can transform into foam cells in endothelium.
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.
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.
Persons afflicted with X-SCID often have infections very early in life, before three months of age. This occurs due to the decreased amount of immunoglobulin G (IgG) levels in the infant during the three-month stage. This is followed by viral infections such as pneumonitis, an inflammation of the lung which produces common symptoms such as cough, fever, chills, and shortness of breath. A telltale sign of X-SCID is candidiasis, a type of fungal infection caused by "Candida albicans". Candidiasis involves moist areas of the body such as skin, the mouth, respiratory tract, and vagina; symptoms of oral candidiasis include difficulty in swallowing, pain on swallowing and oral lesions. Recurrent eczema-like rashes are also a common symptom. Other common infections experienced by individuals with X-SCID include diarrhea, sepsis, and otitis media. Some other common symptoms that are experienced by X-SCID patients include failure to thrive, gut problems, skin problems, and muscle hypotonia.
In some patients symptoms may not appear for the first six months after birth. This is likely due to passive immunity received from the mother in order to protect the baby from infections until the newborn is able to make its own antibodies. As a result, there can be a silent period where the baby displays no symptoms of X-SCID followed by the development of frequent infections.
Histiocytes are derived from the bone marrow by multiplication from a stem cell. The derived cells migrate from the bone marrow to the blood as monocytes. They circulate through the body and enter various organs, where they undergo differentiation into histiocytes, which are part of the mononuclear phagocytic system (MPS).
However, the term "histiocyte" has been used for multiple purposes in the past, and some cells called "histocytes" do not appear to derive from monocytic-macrophage lines. (The term Histiocyte can also simply refer to a cell from monocyte origin outside the blood system, such as in a tissue (as in rheumatoid arthritis as palisading histiocytes surrounding fibrinoid necrosis of rheumatoid nodules).
Some sources consider Langerhans cell derivatives to be histiocytes. The Langerhans cell histiocytosis embeds this interpretation into its name.
X-linked severe combined immunodeficiency (X-SCID) is an immunodeficiency disorder in which the body produces very few T cells and NK cells. In the absence of T cell help, B cells become defective. It is an x-linked recessive trait, stemming from a mutated (abnormal) version of the IL2-RG gene located at xq13.1 on the X-chromosome, which is shared between receptors for IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21.
Leukocytosis can be subcategorized by the type of white blood cell that is increased in number. Leukocytosis in which neutrophils are elevated is neutrophilia; leukocytosis in which lymphocyte count is elevated is lymphocytosis; leukocytosis in which monocyte count is elevated is monocytosis; and leukocytosis in which eosinophil count is elevated is eosinophilia.
An extreme form of leukocytosis, in which the WBC count exceeds 100,000/µL, is leukostasis. In this form there are so many WBCs that clumps of them block blood flow. This leads to ischemic problems including transient ischemic attack and stroke.
Leukocytosis is white cells (the leukocyte count) above the normal range in the blood. It is frequently a sign of an inflammatory response, most commonly the result of infection, but may also occur following certain parasitic infections or bone tumors as well as leukemia. It may also occur after strenuous exercise, convulsions such as epilepsy, emotional stress, pregnancy and labor, anesthesia, and epinephrine administration.
There are five principle types of leukocytosis:
1. Neutrophilia (the most common form)
2. Lymphocytosis
3. Monocytosis
4. Eosinophilia
5. Basophilia
This increase in leukocyte (primarily neutrophils) is usually accompanied by a "left upper shift" in the ratio of immature to mature neutrophils and macrophages. The proportion of immature leukocytes decreases due to proliferation and inhibition of granulocyte and monocyte precursors in the bone marrow which is stimulated by several products of inflammation including C3a and G-CSF.
Although it may indicate illness, leukocytosis is considered a laboratory finding instead of a separate disease. This classification is similar to that of fever, which is also a test result instead of a disease.
"Right shift" in the ratio of immature to mature neutrophils is considered with reduced count or lack of "young neutrophils" (metamyelocytes, and band neutrophils) in blood smear, associated with the presence of "giant neutrophils". This fact shows suppression of bone marrow activity, as a hematological sign specific for pernicious anemia and radiation sickness.
A leukocyte count above 25 to 30 x 10/L is termed a "leukemoid reaction", which is the reaction of a healthy bone marrow to extreme stress, trauma, or infection. It is different from leukemia and from leukoerythroblastosis, in which either immature white blood cells (acute leukemia) or mature, yet non-functional, white blood cells (chronic leukemia) are present in peripheral blood.
The main sign of the disease is life-threatening, recurrent bacterial or fungal soft tissue infections. These infections are often apparent at birth and may spread throughout the body. Omphalitis (infection of the umbilical cord stump) is common shortly after birth. Other signs include delayed separation of the umbilical cord, periodontal disease, elevated neutrophils, and impaired wound healing, but not increased vulnerability to viral infections or cancer. Such patients have fever as the manifestation of infection, inflammatory responses are indolent.
Inflammation (from Latin "") is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, and is a protective response involving immune cells, blood vessels, and molecular mediators. The function of inflammation is to eliminate the initial cause of cell injury, clear out necrotic cells and tissues damaged from the original insult and the inflammatory process, and initiate tissue repair.
The classical signs of inflammation are heat, pain, redness, swelling, and loss of function. Inflammation is a generic response, and therefore it is considered as a mechanism of innate immunity, as compared to adaptive immunity, which is specific for each pathogen. Too little inflammation could lead to progressive tissue destruction by the harmful stimulus (e.g. bacteria) and compromise the survival of the organism. In contrast, chronic inflammation may lead to a host of diseases, such as hay fever, periodontitis, atherosclerosis, rheumatoid arthritis, and even cancer (e.g., gallbladder carcinoma). Inflammation is therefore normally closely regulated by the body.
Inflammation can be classified as either "acute" or "chronic". "Acute inflammation" is the initial response of the body to harmful stimuli and is achieved by the increased movement of plasma and leukocytes (especially granulocytes) from the blood into the injured tissues. A series of biochemical events propagates and matures the inflammatory response, involving the local vascular system, the immune system, and various cells within the injured tissue. Prolonged inflammation, known as "chronic inflammation", leads to a progressive shift in the type of cells present at the site of inflammation, such as mononuclear cells, and is characterized by simultaneous destruction and healing of the tissue from the inflammatory process.
Inflammation is not a synonym for infection. Infection describes the interaction between the action of microbial invasion and the reaction of the body's inflammatory response — the two components are considered together when discussing an infection, and the word is used to imply a microbial invasive cause for the observed inflammatory reaction. Inflammation on the other hand describes purely the body's immunovascular response, whatever the cause may be. But because of how often the two are correlated, words ending in the suffix "" (which refers to inflammation) are sometimes informally described as referring to infection. For example, the word "urethritis" strictly means only "urethral inflammation", but clinical health care providers usually discuss urethritis as a urethral infection because urethral microbial invasion is the most common cause of urethritis.
It is useful to differentiate inflammation and infection as there are many pathological situations where inflammation is not driven by microbial invasion – for example, atherosclerosis, type III hypersensitivity, trauma, ischaemia. There are also pathological situations where microbial invasion does not result in classic inflammatory response—for example, parasitosis, eosinophilia.
Leukocyte adhesion deficiency-1 (LAD1) is a rare and often fatal genetic disorder in humans.
Symptomatic Hyperleukocytosis (Leukostasis) is defined by a tremendously high blast cell count along with symptoms of decreased tissue perfusion. Leukostasis is associated with people who suffer from bone and blood disorders and is very common among people suffering from acute myeloid leukemia or chronic myeloid leukemia. Leukostasis is a pathlogic diagnosis that inhibits efficient flow to the microvasculature of the body. Continued and untreated leukostasis presents respiratory and neurological distress simultaneously and is a medical emergency, with untreated patient mortality rates reaching a minimum of 20 and a maximum of 40 percent.. A leukemia blood cell count greater than 50 x 10^9/ L ((50,000 / microL) or 100 x 10^9 L / (100,000/ microL) signifies hyperleuckocytosis. Symptoms of leukostasis start when blood levels of leukocytes reach over 100 x 10^9 / L (100,000 / microL). As stated before, these counts are critical and associated with Leukemias.
An immune disorder is a dysfunction of the immune system. These disorders can be characterized in several different ways:
- By the component(s) of the immune system affected
- By whether the immune system is overactive or underactive
- By whether the condition is congenital or acquired
According to the International Union of Immunological Societies, more than 150 primary immunodeficiency diseases (PIDs) have been characterized. However, the number of acquired immunodeficiencies exceeds the number of PIDs.
It has been suggested that most people have at least one primary immunodeficiency. Due to redundancies in the immune system, though, many of these are never detected.
The term leukemoid reaction describes an increased
white blood cell count, or leukocytosis, which is a physiological response to stress or infection (as opposed to a primary blood malignancy, such as leukemia). It often describes the presence of immature cells such as myeloblasts or red blood cells with nuclei in the peripheral blood.
It may be lymphoid or myeloid.
An autoimmune disease is a condition arising from an abnormal immune response to a normal body part. There are at least 80 types of autoimmune diseases. Nearly any body part can be involved. Common symptoms include low grade fever and feeling tired. Often symptoms come and go.
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)
When a patient is suffering from symptomatic leuckocytosis, specifically caused by a form a leukemia, it is extremely common to find leukostasis in all their organs. The majority of the time a patient dies from neurological complications (40% of patients die due to neurological conditions) as opposed to particular organ damage. The lungs alone account for approximately 30 percent of leukostasis fatalities. All other organs combined attribute to 30 percent of deaths, with the major outliers being neurological and respiratory failure equating to 70 percent of all death rates. Damage to the microvasculature of the body is the primary cause of death by leukostasis. Microvasculatre damage to the lungs is only second to neurological damage because the body is already suffering from hypoxic conditions, which leads to lung tissue damage as the second leading cause of fatalities.
Pulmonary signs - Dyspnea and Hypoxia with or without diffuse interstitial or alveolar infiltrates on imaging studies.
Neurological signs - visual changes, headache, dizziness, tinnitus, gait instability, confusion, somnolence, coma.
The most common symptom is the patient is usually febrile, which is often linked with inflammation and possible infection.
Less common symptoms include electroencephalographic, signs of myocardial ischemia / right ventricular overload, increased renal insufficiency, priapism, acute limb ischemia and bowel infarction.
LAD was first recognized as a distinct clinical entity in the 1970s. The classic descriptions of LAD included recurrent bacterial infections, defects in neutrophil adhesion, and a delay in umbilical cord sloughing. The adhesion defects result in poor leukocyte chemotaxis, particularly neutrophil, inability to form pus and neutrophilia.
Individuals with LAD suffer from bacterial infections beginning in the neonatal period. Infections such as omphalitis, pneumonia, gingivitis, and peritonitis are common and often life-threatening due to the infant's inability to properly destroy the invading pathogens. These individuals do not form abscesses because granulocytes cannot migrate to the sites of infection.
Acute inflammation is a short-term process, usually appearing within a few minutes or hours and begins to cease upon the removal of the injurious stimulus. It involves a coordinated and systemic mobilization response locally of various immune, endocrine and neurological mediators of acute inflammation. In a normal healthy response, it becomes activated, clears the pathogen and begins a repair process and then ceases. It is characterized by five cardinal signs:
An acronym that may be used to remember the key symptoms is "PRISH", for pain, redness, immobility (loss of function), swelling and heat.
The traditional names for signs of inflammation come from Latin:
- Dolor (pain)
- Calor (heat)
- Rubor (redness)
- Tumor (swelling)
- Functio laesa (loss of function)
The first four (classical signs) were described by Celsus (ca. 30 BC–38 AD), while "loss of function" was probably added later by Galen. However, the addition of this fifth sign has also been ascribed to Thomas Sydenham and Virchow.
Redness and heat are due to increased blood flow at body core temperature to the inflamed site; swelling is caused by accumulation of fluid; pain is due to the release of chemicals such as bradykinin and histamine that stimulate nerve endings. Loss of function has multiple causes.
Acute inflammation of the lung (usually caused in response to pneumonia) does not cause pain unless the inflammation involves the parietal pleura, which does have pain-sensitive nerve endings.