Flashcards in White Cell Disorders - Leukopenia, Leukocytosis, Lymphadenitis Deck (19):
How are white cell disorders divided?
Two broad categories: Proliferative and Leukopenias
Proliferative can be reactive (in the setting of infection or inflammatory processes, normal host response, common) or neoplastic.
What does leukopenia usually result from?
What does agranulocytosis result in?
An increased susceptibility to bacterial and fungal infections.
What are the two broad causes of neutropenia?
1) Decreased production 2) Increased sequestration in the peripheries
What are the causes of ineffective granulopoieses?
1) Suppression of haematopoietic stem cells - aplastic anaemia, infiltrative marrow disorders e.g. tumour and granulomatous disease. Accompanied by anaemia and thrombocytopenia.
2) Suppression of committed granulocytic precursors - exposure to drugs
3) Ineffective haematpoiesis - megaloblastic anaemias and myelodysplastic syndromes (defective precursors die in the marrow)
4) Congenital disorders - Rare, e.g. Kostmann syndrome
What are the causes of accelerated destruction of neutrophils?
1) Immunologically mediated injury to neutrophils - idiopathic, associated with well-defined immunological disorders (e.g.SLE), or exposure to drugs
2) Splenomegaly - leads to sequestration of neutrophils and a modest neutropenia, sometimes anaemia and often neutropenia
3) Increased peripheral utilisation - overwhelming bacterial fungal or rickettsial infections
What is the most common cause of agranulocytosis?
Drug induced - both desired from chemotherapeutic agents and idiosyncratically from other drugs, including:
- aminopyrine (a pyrazolone with analgesic, anti-inflammatory, and antipyretic properties)
- chloramphenicol (bacteriostatic antibiotic)
- sulfonamides (a function group that is the chemical basis of a number of drugs including some antibiotics, sulfonylureas and thiazide diuretics)
- chlorpromazine (antipsychotic)
- thiouracil (inhibits thyroid activity by blocking the enzyme thyroid peroxidase)
-phenylbutazone (NSAID, no longer used in humans)
Describe the morphology of bone marrow in agranulocytosis.
Vary with cause.
Excessive preipheral destruction leads to hyper cellular marrow.
Ineffective granulopoieses (megaloblastic anaemias and myelodysplastic syndromes) leads to hypercellularity.
Suppression or destruction of granulocyte precursors by drugs leads to hypocellularity.
What are the clinical features of neutropenia?
The signs and symptoms are generally related to infection.
Malaise, chills, fever, weakness and fatiguability.
Agranulocytosis can lead to overwhelming infection which can lead to death within hours to days.
Infections are often fulminant so broad spec antibiotics are required.
Neutropenia may also be treated with G-CSF (granulocyte colony stimulating factor)
What is leukocytosis?
Increase in the number of white cells in the blood
Is leukocytosis common?
Yes, it is a normal reaction to a number of inflammatory states.
What are the common mechanisms and causes of leukocytosis?
1) Increased production in the marrow - chronic infection or inflammation (GF dependent), paraneoplastic (hodgkin's lymphoma, growth factor dependent), myeloproliferative disorders (e.g. chronic myeloid leukaemia, GF independent)
2) Increased release from marrow stores - endotoxemia, infection, hypoxia
3) Decreased margination - exercise, catecholamines
4) Decreased extravasation into tissues - glucocorticoids
Which is the most important cause of leukocytosis?
Infection - in acute infection mature granulocytes leave the bone marrow pool through the stimulation of TNF and IL1, the prolonged infection leads to high levels of TNF, IL1 and other factors that stimulate the release of specific growth factors for different types of leukocyte, leading to a proliferation of a specific type of cell for a specific type of infection.
Name the specific types of leukocytosis and their causes.
1) Neutrophilic leukocytosis - acute bacterial infections, especially pyogenic organism, sterile inflammation e.g. tissue necrosis in MI and burns
2) Eosinophilic leukocytosis - allergic disorders (e.g. asthma, hay fever, parasitic infections), drug reactions, certain malignancies (hodgkins and some non-hodgkin's lymphoma), autoimmune disorders (e.g. pemphigus, dermatitis herpetiformens) and some vasculitides, atherothrombolic disease (transient)
3) Basophilic leukocytosis - rare, often indicative of myeloproliferative disorders.
4) Monocytosis - chronic infections (TB), bacterial endocarditis, rickettsiosis and malaria, autoimmune disorders (SLE), IBD
5) Lymphocytosis - accompanies monocytosis in chronic disease, viral infections, Bordetella pertussis infection
What is lymphadenitis? Where does it occur?
Swollen secondary lymph tissue, (as opposed to the primary tissue of bone marrow and thymus) which includes lymph nodes, spell, tonsils, adenoids and Peyer's patches.
What is the normal pathogenesis of lymphadenitis?
- Activation of resident immune cells, leads to morphologic changes
- Within several days of antigenic stimulation, primary follicles enlarge and develop pale germinal centres (B cell training zones). Para cortical T cell zones can also enlarge
What are the most common forms of lymphadenitis?
Acute and chronic nonspecific lymphadenitis, each with it's own pattern of change.
What drains where in acute lymphadenitis?
How does it present?
Cervical region drains the mouth, teeth and tonsils
Axillary or inguinal regions drain the peripheries.
Mesenteric lymph nodes flare in acute pancreatitis.
Acute mesenteric adenines may occur after infection, mimicking appendicitis.
Systemic viral infections (particularly in children) and bacteraemia of produce acute generalised lymphadenopathy.
Nodes are enlarged and painful. Suppurative infections may penetrate the capsule and communicate with the skin producing a draining sinus.