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ANP 370 Summary Robbins Basic Pathology, ISBN: 9781437717815 Pathology (ANP 370)
This is a comprehensive summary of theme 3 of Anatomical Pathology. It will help get you on the right track to get a distinction in this course.
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Theme 3 Summary HaematopathologyUnit 1. Disorders of White Blood Cells
The terms “leukopenia”, “neutropenia”, “leukocytosis” and “lymphadenitis” are correctly defined.
Basic aspects of the aetiology, pathogenesis and clinical manifestations of leukopenia, neutropenia, leukocytosis, and
lymphadenitis are correctly described.
Leukopenia
Leukopenia is a decrease circulating granulocytes, the most numerous circulating white cells.
Neutropenia/Agranulocytosis
A reduction in the number of granulocytes in blood is known as neutropenia or, when severe, agranulocytosis.
Neutropenic persons are susceptible to severe, potentially fatal bacterial and fungal infections.
Pathogenesis
The mechanisms underlying neutropenia can be divided into two broad categories:
Decreased granulocyte production
o Reductions in granulopoiesis are most often caused by marrow hypoplasia (aplastic anemia or chemo) or
extensive replacement of the marrow by tumor (leukemia)
o Alternatively, neutrophil production may be suppressed while other blood lineages are unaffected. This
is most often caused by certain drugs or by neoplastic proliferations of cytotoxic T cells and natural killer
(NK) cells (so-called “large granular lymphocytic leukemia”)
Increased granulocyte destruction
o This can be encountered with immune-mediated injury (triggered in some cases by drugs) or in
overwhelming bacterial, fungal, or rickettsia infections resulting from increased peripheral use
o Splenomegaly also can lead to the sequestration and accelerated removal of neutrophils
Clinical Features
Infections constitute 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)
Owing to the lack of leukocytes, such lesions often contain large masses or sheets of microorganisms
Reactive Leukocytosis
An increase in the number of circulating white blood cells, due to a variety
of inflammatory states caused by microbial and nonmicrobial stimuli.
Leukocytoses are classified according to the particular white cell series
that is affected.
Infectious Mononucleosis
an acute, self-limited disease of adolescents and young adults that is
caused by Epstein Barr virus (EBV), a member of the herpesvirus family.
The infection is characterized by:
Fever, sore throat, and generalized lymphadenitis (inflammation
of the lymph nodes)
A lymphocytosis of activated, CD8+ T cells
Even though infected children mount an immune response, most remain
asymptomatic and more than half continue to shed virus, usually for life.
, Pathogenesis
Transmission to usually involves direct oral contact (e.g. kissing). The virus initially infects oropharyngeal epithelial cells
and then spreads to underlying lymphoid tissue (tonsils and adenoids), where mature B cells are infected. The infection
of B cells takes one of two forms:
Latent
o B cells that are latently infected with EBV become “activated” and proliferate as a result of the action of
several viral proteins
o These cells disseminate in the circulation and secrete
antibodies with unusual specificities, including the
antibodies that recognize sheep red cells that are detected
in diagnostic tests for mononucleosis
o During acute infections, EBV is shed in the saliva
Lytic in a minority of cells whereby the virus replicates and releases
more copies of itself
The host T cell response controls the proliferation of EBV-infected B cells
and the spread of the virus. Early in the course of the infection, IgM
antibodies are formed against viral capsid antigens. Later the serologic
response shifts to IgG antibodies, which persist for life. Virus-specific CD8+
T cells appear in the circulation as atypical lymphocytes, a finding that is
characteristic of mononucleosis.
Impaired T cell immunity places patients at high risk for EBV-driven B cell
proliferations.
Clinical Features
Classically manifests with fever, sore throat (white coating on tonsils), and
lymphadenitis
Sometimes there is little or no fever and only fatigue and lymphadenopathy
exist, raising the specter of lymphoma
The diagnosis depends on the following, in increasing order of specificity
o The presence of atypical lymphocytes in the peripheral blood
o A positive heterophil reaction (Monospot test)
o A rising titer of antibodies specific for EBV antigens
Reactive Lymphadenitis
Infections and nonmicrobial inflammatory stimuli often activate immune cells residing in lymph nodes, which act as
defensive barriers. Any immune response against foreign antigens can lead to lymph node enlargement
(lymphadenopathy).
1. Acute nonspecific lymphadenitis
This form of lymphadenitis may be isolated to a group of nodes draining a local infection, or be generalized, as in
systemic infectious and inflammatory conditions.
2. Chronic nonspecific lymphadenitis
Depending on the causative agent, chronic nonspecific lymphadenitis can assume one of three patterns
a. Follicular hyperplasia
i. This pattern occurs with infections or inflammatory processes that activate B cells, which
migrate into B cell follicles and create the follicular (or germinal center) reaction.
ii. Disease examples include RA, toxoplasmosis, and early HIV infection
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