WBC 1 Flashcards
(47 cards)
Leukopenia
Leukopenia results most commonly from a decrease in granulocytes, which are the most prevalent circulating white cells.
Lymphopenias are much less common; they are associated with
congenital immunodeficiency diseases or
are acquired such as advanced human immunodeficiency virus (HIV) infection or treatment with corticosteroids.
Only the more common leukopenias that affect granulocytes are discussed here.
Neutropenia/Agranulocytosis
NON-NEOPLASTIC DISORDERS OF WHITE CELLS
Leukopenia
Neutropenia/Agranulocytosis
Reactive Leukocytosis
Infectious Mononucleosis
Reactive Lymphadenitis
Acute Nonspecific Lymphadenitis
Chronic Nonspecific Lymphadenitis
Cat Scratch Disease
Neutropenia/Agranulocytosis
A reduction in the number of granulocytes in blood is known as neutropenia or sometimes, when severe, as agranulocytosis.
Characteristically, the total white cell count is reduced to 1000 cells/μL and in some instances to as few as 200 to 300 cells/μL.
Affected persons are extremely susceptible to bacterial and fungal infections, which can be severe enough to cause death.
Etiology and pathogenesis of neutropenia/agranulocytosis
The mechanisms that cause neutropenia divided into two categories:
- Inadequate or ineffective granulopoiesis.
- Accelerated removal or destruction of neutrophils.
Neutropenia/Agranulocytosis:Inadequate or ineffective granulopoiesis
is a manifestation of generalized marrow failure, which occurs in aplastic anemia and a variety of leukemias.
Cancer chemotherapy agents also produce neutropenia by inducing transient marrow aplasia.
some neutropenias are isolated, with only the differentiation of committed granulocytic precursors being affected. These forms of neutropenia are most often caused by certain drugs or, more uncommonly, by neoplastic proliferations of cytotoxic T cells and natural killer (NK) cells.
Neutropenia/Agranulocytosis: Accelerated removal or destruction of neutrophils
immune-mediated injury to neutrophils (triggered in some cases by drugs), or it may be idiopathic.
Increased peripheral utilization can occur in overwhelming bacterial, fungal, or rickettsial infections.
An enlarged spleen can also lead to sequestration and accelerated removal of neutrophils.
Neutropenia/Agranulocytosis: clinical course
The initial symptoms are often malaise, chills, and fever, with subsequent marked weakness and fatigability.
Infections constitute to the major problem.
They commonly take the form of ulcerating, necrotizing lesions of the gingiva, floor of the mouth, buccal mucosa, pharynx, or other sites within the oral cavity (agranulocytic angina).
Treatment:
removal of the offending drug and control of infections,
administration of granulocyte colony-stimulating factor, which stimulates neutrophil production by the bone marrow.
Reactive leukocytosis
An increase in the number of white cells is common in a variety of reactive inflammatory states caused by microbial and nonmicrobial stimuli.
in some cases reactive leukocytosis may mimic leukemia.
Infectious mononucleosis, a form of lymphocytosis caused by Epstein-Barr virus (EBV) infection, merits separate consideration because it gives rise to a distinctive syndrome.
Causes of leukocytosis
- Neutrophilic Leukocytosis
Acute bacterial infections, especially those caused by pyogenic organisms; sterile inflammation caused by, for example, tissue necrosis (myocardial infarction, burns) - Eosinophilic Leukocytosis (Eosinophilia)
Allergic disorders such as asthma, hay fever, allergic skin diseases (e.g., pemphigus, dermatitis herpetiformis); parasitic infestations; drug reactions; certain malignancies (e.g., Hodgkin disease and some non-Hodgkin lymphomas); collagen vascular disorders and some vasculitides; atheroembolic disease (transient) - Basophilic Leukocytosis (Basophilia)
Rare, often indicative of a myeloproliferative disease (e.g., chronic myelogenous leukemia) - Monocytosis
Chronic infections (e.g., tuberculosis), bacterial endocarditis, rickettsiosis, and malaria; collagen vascular diseases (e.g., systemic lupus erythematosus); and inflammatory bowel diseases (e.g., ulcerative colitis) - Lymphocytosis:
Accompanies monocytosis in many disorders associated with chronic immunologic stimulation (e.g., tuberculosis, brucellosis); viral infections (e.g., hepatitis A, cytomegalovirus, Epstein-Barr virus); Bordetella pertussis infection
Infectious Mononucleosis
In the Western world, infectious mononucleosis is an acute, self-limited disease of adolescents and young adults that is caused by B lymphocytotropic EBV, a member of the herpesvirus family.
The infection is characterized by
1.fever, sore throat, and generalized lymphadenitis;
- an increase of lymphocytes in blood, many of which have an atypical morphology;
- an antibody and T cell response to EBV.
It should be noted that cytomegalovirus infection induces a similar syndrome, which can be differentiated only by serologic methods.
Infectious Mononucleosis: Epidemiology and Immunology
Transmission to a seronegative “kissing cousin” usually involves direct oral contact.
It is hypothesized (but not proven) that the virus initially infects oropharyngeal epithelial cells and then spreads to underlying lymphoid tissue (tonsils and adenoids), where B lymphocytes, which have receptors for EBV, are infected.
The infection of B cells takes one of two forms.
1.In a minority of cells, the infection leads to viral replication and eventual cell lysis accompanied by the release of virions.
2.In most cells, however, the infection is nonproductive, and the virus persists in latent form as an extrachromosomal episome. B cells that are latently infected with EBV undergo polyclonal activation and proliferation, as a result of the action of several EBV proteins
These cells disseminate in the circulation and secrete antibodies with several specificities, including the well-known heterophil anti-sheep red cell antibodies that are recognized in diagnostic tests for mononucleosis.
During this early acute infection, EBV is shed in the saliva; it is not known if the source of these virions is oropharyngeal epithelial cells or B cells.
Virus-specific cytotoxic T cells appear as atypical lymphocytes in the circulation, a finding that is characteristic of acute mononucleosis.
Morphology of infectious mononucleosis
Signs/symptoms: fever, swollen lymph nodes, fatigue, sore throat, chills, malaise, headache, loss of appetite,ache, cough, reddening of throat, nausea, abdm pain, photophobia, spleen enlargement.
The major alterations involve the blood, lymph nodes, spleen, liver, central nervous system, and, occasionally, other organs.
There is peripheral blood leukocytosis, with a white cell count that is usually between 12,000 and 18,000 cells/μL.
Typically more than half of these cells are large, atypical lymphocytes,
The lymph nodes are enlarged throughout the body, including the posterior cervical, axillary, and groin regions.
Histologically, the enlarged nodes are flooded by atypical lymphocytes
Occasionally, cells resembling Reed-Sternberg cells, the hallmark of Hodgkin lymphoma, are present. Because of these atypical features, special tests are sometimes needed to distinguish the reactive changes of mononucleosis from malignant lymphoma.
Morphology of infectious Mononucleosis II
The spleen is enlarged in most cases, weighing between 300 and 500 gm.
such spleens are fragile and prone to rupture after even minor trauma.
Liver function is almost always transiently impaired .
Histologically, atypical lymphocytes are seen in the portal areas and sinusoids, and scattered, isolated cells or foci of parenchymal necrosis filled with lymphocytes may be present.
This histologic picture can be difficult to distinguish from other forms of viral hepatitis
Clinical course for infectious mononucleosis
mononucleosis classically presents as fever, sore throat, lymphadenitis, and the other features mentioned earlier,
atypical presentations are not unusual.
It can appear with little or no fever and only malaise, fatigue, and lymphadenopathy, raising the specter of lymphoma; as a fever of unknown origin, unassociated with significant lymphadenopathy or other localized findings; as hepatitis that is difficult to differentiate from one of the hepatotropic viral syndromes
or as a febrile rash resembling rubella.
Clinical course for infectious mononucleosis II
the diagnosis depends on the following findings, in increasing order of specificity:
- lymphocytosis with the characteristic atypical lymphocytes in the peripheral blood,
- a positive heterophil reaction (monospot test),
- a rising titer of antibodies specific for EBV antigens
In most patients, mononucleosis resolves within 4 to 6 weeks
complications
the most common of these is hepatic dysfunction, associated with jaundice, elevated hepatic enzyme levels, disturbed appetite, and, rarely, even liver failure.
Other complications involve the nervous system, kidneys, bone marrow, lungs, eyes, heart, and spleen (including fatal splenic rupture).
Characteristics of infectious mononucleosis
The importance of T cells and NK cells in the control of EBV infection is driven home by X-linked lymphoproliferative syndrome,
a rare inherited immunodeficiency
characterized by inability to mount an immune response against EBV.
Most affected boys have a mutation in the SH2D1A gene, which encodes a signaling protein that is important in the activation of T cells and NK cells.
On exposure to EBV, more than 50% of these boys develop an overwhelming infection that is usually fatal.
Of the remainder, some develop lymphoma or hypogammaglobulinemia, the basis of which is not understood.
Reactive Lymphadenitis
Infections and nonmicrobial inflammatory stimuli not only cause leukocytosis but also involve the lymph nodes, which act as defensive barriers.
Any immune response against foreign antigens is often associated with lymph node enlargement (lymphadenopathy).
Acute Nonspecific Lymphadenitis
Chronic Nonspecific Lymphadenitis
Acute Nonspecific Lymphadenitis
This form of lymphadenitis may be confined to a local group of nodes draining a focal infection, or be generalized in systemic bacterial or viral infections.
Morphology
Macroscopically, inflamed nodes in acute nonspecific lymphadenitis are swollen, gray-red, and engorged.
Histologically, there are large germinal centers containing numerous mitotic figures.
With severe infections, the centers of follicles can undergo necrosis, resulting in the formation of an abscess.
Affected nodes are tender and, when abscess formation is extensive, become fluctuant. The overlying skin is frequently red, and penetration of the infection to the skin can produce draining sinuses.
With control of the infection,
the lymph nodes can revert to their normal appearance
if damaged by the immune response, undergo scarring.
Chronic Nonspecific Lymphadenitis
This condition can assume one of three patterns, depending on the causative agent: follicular hyperplasia, paracortical hyperplasia, or sinus histiocytosis.
Morphology
Follicular Hyperplasia. This pattern is associated with infections or inflammatory processes that activate B cells, which enter into B-cell follicles and create the follicular (or germinal center) reaction.
Causes of follicular hyperplasia include rheumatoid arthritis, toxoplasmosis, and the early stages of HIV infection.
Findings that favor a diagnosis of follicular hyperplasia are
1.the preservation of the lymph node architecture, with normal lymphoid tissue between germinal centers;
2.variation in the shape and size of the lymphoid nodules;
3.a mixed population of lymphocytes at various stages of differentiation; and
4.prominent phagocytic and mitotic activity in germinal centers.
Chronic Nonspecific Lymphadenitis
Paracortical Hyperplasia. This pattern is characterized by reactive changes within the T-cell regions of the lymph node.
Paracortical hyperplasia is encountered in viral infections (such as EBV), following certain vaccinations (e.g., smallpox), and in immune reactions induced by certain drugs (especially phenytoin).
Sinus Histiocytosis. This reactive pattern is characterized by distention and prominence of the lymphatic sinusoids, owing to a marked hypertrophy of lining endothelial cells and an infiltrate of macrophages (histiocytes). Sinus histiocytosis is often encountered in lymph nodes draining cancers and may represent an immune response to the tumor or its products.
Cat Scratch Disease
a self-limited lymphadenitis caused by the bacterium Bartonella henselae.
primarily a disease of childhood; 90% of the patients are younger than 18 years of age.
It presents as regional lymphadenopathy, most frequently in the axilla and neck.
The nodal enlargement appears approximately 2 weeks after a feline scratch
In most patients the lymph node enlargement regresses over the next 2 to 4 months.
Rarely, patients develop encephalitis, osteomyelitis, or thrombocytopenia.
Cat Scratch Disease:Morphology
The anatomic changes in the lymph node in cat scratch disease are quite characteristic.
Initially, sarcoid-like granulomas are formed,
then undergo central necrosis associated with the accumulation of neutrophils.
These irregular stellate necrotizing granulomas are similar in appearance to those seen in certain other infections, such as lymphogranuloma venereum.
The microbe is extracellular and can be visualized only with silver stains or electron microscopy.
The diagnosis is based on a history of exposure to cats, the clinical findings, a positive skin test to the microbial antigen, and the distinctive morphologic changes in the lymph nodes.
CBC Diagnostics: Normal CBC Variations
Hbg and HCT are highest at birth (20 g/100 mL and 60%, respectively).
The values fall steeply to a minimum at 3 mo (9.5 g/100 mL and 32%).
Then they slowly rise to near adult levels at puberty;
both values are higher in men.
A normal decrease occurs in pregnancy.
The number of WBCs is highest at birth (mean of 25,000/mm3)
slowly falls to adult levels by puberty.
Lymphs predominate (as much as 60% from the second week of life until age 5–7 y, when polys begin to predominate).
CBC Diagnostics:The Left Shift
The degree of nuclear lobulation of PMNs indicates cell age.
A predominance of immature cells with only one or two nuclear lobes separated by a thick chromatin band is called a “shift to the left.”
Conversely, a predominance of cells with four nuclear lobes is called a “shift to the right.”
(For historical information, left and right designations come from the formerly used manual lab counters, in which the keys for entering stabs were located on the left of the keyboard.)
As a rule, 55–80% of PMNs have two to four lobes. More than 20 five-lobed cells/100 WBCs suggests megaloblastic anemia, a six- or seven-lobed poly being diagnostic.
