lecture 9 Flashcards
Both hereditary and acquired disorders are associated with morphologic abnormalities of:
neutrophils
what part of the cell could be defected/ abnormal?
- nucleus
- cytoplasm
nuclear defects include:
- hyposegmentation
- hypersegmentation
cytoplasmic abnormalities include:
- inclusions
- hypogranular cytoplasm
- hypergranular cytoplasm
how long does it take for a blast to mature into a segmented neutrophil? and where?
(normally)
- 7-10 days
- in the BM
in septecemia, what happens to the BM function and nb of neutrophils?
(all details)
- BM is stimulated to produce neutrophils at a faster rate
- neutrophils are released from BM before they are completely mature
- cytoplasm will contain more RNA and primary granules
- residual RNA occur in small islets called Dohle bodies
what are the dohle bodies?
- residual RNA in small islets
- small light blue staining areas in the neutrophil cytoplasm (near cytoplasmic membrane)
what are the toxic granules?
- primary granules which persisted in large numbers have been called by mistake “toxic granules
- but these are in fact the promyelocyte granules which have persisted till the late stage because the neutrophil didn’t have enough time to lose them, or due to skipped divisions during the development of the neutrophil
what happens to the maturation time, nb of divisions, and neutrophil release under certain reactive or stressful conditions?
- maturation time may be shortened
- divisions may be skipped
- release into the blood may occur prematurely
what happens when the damage to the neutrophils is more severe?
- enzymes within granules are released into the cytoplasm
- causes severe vacuolization of cytoplasm (holes) as a result of active phagocytosis
- clear, unstained, round areas in cytoplasm
list the different congenital conditions of neutrophils
- hereditary hypersegmentation
- pelger-huet anomaly
- may-hegglin anomaly
- alder-reilly anomaly
- chediak-higashi anomaly
hereditary hypersegmentation key points
- autosomal dominant condition
- hypersegmentation above 5 segments
- rare
- entirely harmless
- not associated with any disease
- seen in all neutrophils
what is pelger-huet anomaly?
- autosomal dominant condition
- hyposegmentation of neutrophils
- patient could be homozygout or heterozygout
- entirely harmless
- neutrophils function normally
- what are the 2 states in pelger-huet anomaly?
- what difference do they have?
- what do they have common?
- heterozygout and homozygout
- homozygout –> nucleus rounded/ unsegmented
heterozygout –> nucleus bilobed (all neutrophils have no more than a bilobed nucleus) - in both states, chromatin is coarsely clumped
what causes pelger-huet anomaly?
- mutation in the gene that controls the segmentation of neutrophils
- results in failure of neutrophils to segment
why is it practically important to recognize pelger-huet anomaly?
- so that it is not confused with a shift to the left
- these cells are fully mature cells that look morphologically immature because they are unsegmented or hyposegmented
what is may-hegglin anomaly?
- autosomal dominant condition
- inherited abnormality of granulocyte and monocyte morphology
- characterized by:
1. large gray-blue staining inclusions in the cytoplasm
2. variable leukopenia, thrombocytopenia, & giant platelets with low nb of granules
may-hegglin anomaly affects neutrophils only
(T/F)
false, all granulocytes and monocytes
what problems do people with may-hegglin could develop?
- some may develop hemorrhagic problems of variable severity
- at higher risk of infection
most people do not experience clinical symptoms
are the inclusions of may-hegglin anomaly similar to dohle bodies? if yes, how are they similar and how do they differ?
similarities:
* they are similar in appearance & composition
* they mainly consist of RNA derived from RER
differences:
* may-hegglin inclusions are larger & discrete
* they may be round or spindle-shaped
* found in large % of cells, not just neutrophils
RNA found in dohle bodies and May-hegglin inclusions are derived from the smooth endoplasmic reticulum
(T/F)
false, rough
what is alder-reilly anomaly?
- autosomal recessive trait
- inherited abnormality of granulocyte, monocyte, & lymphocyte morphology
- presence of abnormally large azurophilic and basophilic granules
- resembling severe toxic granulation in the cytoplasm
does the alder-reilly bodies (inclusions) affect function?
no
alder-reilly anomaly is in association with what type of disease?
- storage diseases in which protein-carbohydrate complexes called mucopolysaccaride accumulate in the cytoplasm of tissues & blood cells
- due to lack of lysosomal enzymes that break down these complexes
what is the chediak-higashi anomaly?
- autosomal recessive condition
- inherited abnormality of granulocyte function
- characterized by abnormal killing
- important anomaly but very rare
- very serious
- characteristic feature: granules of all granular cells tend to fuse & form large granules
chediak-higashi anomaly is associated with what conditions?
- associated with increased susceptibility to infections and bleeding tendencies
- normal platelet counts, but abnormal platelet function
how are granules fused in neutrophils, lymphocytes, and promyelocytes?
(in chediak-higashi anomaly)
in neutrophils:
* fusion of primary and secondary granules to form extremely coarse structures
* instead of having fine granules, we will have 10-15 huge granules
lymphocytes:
* fusion of nonspecific granules onto a single huge solitary granule
promyelocyte:
* primary granules fuse to form 3-4 clumps surrounded by vacuoles (strictly characteristic)
what happens to the function of granulocytes when the granules are fused?
(in chediak-higashi anomaly)
- they are unable to degranulate and release their digestive enzymes when exposed to bacterial infections –> poor bacterial killing
- children are prone to repeated bacterial infections
- eventually die from 1 of those infections
- who survive the recurrent infections develop an “accelerated” phase of the disease: a progressive lymphoma like disease
what are downy cells?
when do they occur?
what are the 3 types?
- abnormal lymphocytes
- in some disease conditions such as viral infections
- the 3 types are:
1. atypical lymphocyte
2. blast-like lymphocyte with hyperbasophilic cytoplasm
3. plasmacytoid lymphocyte
what congenital conditions (anomalies) have an autosomal dominant trait?
- hereditary hypersegmentation
- pelger-huet anomaly
- may-hegglin anomaly
what congenital conditions (anomalies) have an autosomal recessive trait?
- alder-reilly anomaly
- chediak-higashi anomaly
pelger-huet is an inherited abnormality of granulocyte function
(T/F)
false, chediak-higashi
alder-reilly anomaly affects granulocytes and monocytes only
(T/F)
false, and lymphocytes
what cells does may-hegglin anomaly affect?
granulocytes and monocytes
WBC anomalies can be divided into 2 broad categories:
- quantitative or numerical anomalies
- qualitative or morphological anomalies
what is the normal range for WBC count?
4,000-11,000/mm^3
what is leukocytosis?
- WBC count above normal range
- increase in one or more cell types, or by the presence of abnormal cell types
leukocytosis is usually a sign of what conditions?
- inflammatory response
- infections
- parasitic infections
- exercise
- epilepsy
- emotional stress
- pregnancy
- labour
what are the 5 principle types of leukocytosis?
- neutrophilia
- lymphocytosis
- monocytosis
- eosinophilia
- basophilia
what is the most common form of leukocytosis?
neutrophilia
cytosis always refers to:
elevation in cell count
if WBC count drops below 4,000/mm^3, we call the condition:
leukopenia
(penia refers to depression in cell count)
decrease in neutrophils, lymphocytes, all cell types, we call these conditions:
- neutropenia
- lymphopenia
- pancytopenia
does the decrease in eosinophils, basophils, or monocytes cause leukopenia?
no, since they are normally present in low nbs
if leukopenia is severe enough to result in almost complete disappearance of neutrophils, we call the condition:
agranulocytosis
what is agranulocytosis?
- almost complete disappearance of neutrophils
- extremely dangerous condition
- person cannot react to infections
what cells have the greatest impact on the total WBC count?
neutrophils, since they normally constitute the largest % of cells
what is the life span of neutrophils? (from myeloblast to death)
9-10 days
the neutrophil spends its life in 3 main areas of the body:
- passing from the BM
- to peripheral blood
- into the tissues
movement does not reverse
neutrophil population in the BM can be subdivided into 2 groups:
- mitotic pool
- post-mitotic pool (maturation & storage pool)
the mitotic pool refers to:
cells undergoing proliferation & differentiation (myeloblasts, promyelocytes, myelocytes)
cells stay in the mitotic pool for how long? how many divisions do they undergo?
- for few days
- 4-5 divisions
at what stage is the cell no longer capable of mitosis?
metamyelocyte stage
spends its time in maturation
under certain reactive or stressful conditions, what happens to the maturation time and nb of divisions?
(+ release)
- maturation time may be shortened
- division may be skipped
- released into the blood prematurely
how long to cells spend in the maturation and storage pool?
5-7 days maturing
what type of cells make up the post-mitotic pool?
fully differentiated mature neutrophils
once in the peripheral blood, neutrophils are divided into 2 pools, what are they:
- 50% of neutrophils circulate freely –> making up the circulationg pool
- other 50% adhere to the walls of blood vessels –> making up the marginating pool
cells in the marginating pool are not included in the WBC count
(T/F)
true
cells in the marginating pool are not included in the WBC count
(T/F)
true
the number of neutrophils counted in a WBC count and differential count represents 100% of the neutrophils in PB
(T/F)
false, represents only half the nb actually present in PB since cells in the marginal pool are not included in the WBC count
do neutrophils in circulating and marginal pools change pools or remain in the same pool?
neutrophils are continually changing between the marginal and circulating pools
(marginating cells can enter circulating pool, & vice versa)
what is neutrophilia? (>? /mm^3)
- increase in the nb of neutrophils
- > 8,000 /mm^3
what is the ANC?
what is the formula of it?
- aboslute neutrophil count (ANC) is the measure of the nb of neutrophil granulocytes present in blood
- AC= WBC (/mm^3) x % neutrophils /100
conditions associated with neutrophilia may be divided into 3 categories:
- physiologic
- pathologic
- hereditary
what causes physiologic neutrophilia?
give examples of common physiologic causes (conditions)
caused by a shift of marginating cells to the circulating pool in relation to hormonal release
* pregnancy
* physical exercise
* emotional stress
* newborns
physiologic neutrophilia is not characterized by any significant increase in __?
immature cells
physiologic neutrophilia is transient, lasting only a few hours
(T/F)
true
its a very rapid phenomenon
1 physiological cause of neutrophilia is newborns
(T/F)
true
what 2 hormones causes the shift of marginating cells into the circulation
- adrenalin (epinephrine)
- hydrocortisone
nb of neutrophils almost double
what causes pathologic neutrophilia?
give examples of certain conditions
any pathologic condition that stimulates increased marrow output of neutrophils
* infections
* inflammation
* metabolic disorders
* malignancy
* CSFs, ILs
pathologic neutrophilia is accompanied by:
a shift to the left (increased % of immature cells)
mobilization of the maturation/storage compartment can occur within days in pathologic neutrophilia (shift to the left)
(T/F)
false, can occur within hours
in more severe conditions, for neutrophilia to be sustained, ____BM production must occur, up to ____as a response to ____accompanied by ____release of cells, and ____.
- increased
- fivefold
- cytokines
- premature
- a shift to the left
increase BM production occurs after few days
what is the primary WBC that responds to bacterial infections?
neutrophils
what is the most common cause of pathologic neutrophilia?
specify + what bacterias
- bacterial infections
- especially pyogenic infections
- caused by streptococci, staphylococci, pneumococci
more moderate neutrophilic responses are characteristic of infections caused by:
- bacilli
- viruses
- rickettsiae
- parasites
in acute infections, leukocyte counts are:
15,000-20,000/mm^3
(>50,000/mm^3 occasionally occur)
what is a leukemoid reaction?
an increase in WBC count with some immature cells
leukemoid reaction is similar to what occurs in people with:
leukemia (CML)
however this reaction is due to an infection/disease and not cancer
blood counts will return to normal when the underlying pathologic condition is not treated
(T/F)
false, when it is treated
all bacterial infections result in neutrophilic leukocytosis (neutrophilia)
(T/F)
false, not all
some bacterial infections result in neutropenia
(T/F)
true
what type of bacterial infections result in neutropenia?
salmonellosis and brucellosis
what types of inflammatory processes cause neutrophilia?
list all the examples
- appendicitis
- pancreatitis
- colitis
- myocardial infarction
- surgical/traumatic wounds
- gout (joint inflammation)
- thermal injury (burns)
- severe hemolysis
- tissue destruction
- rheumatoid arthritis
- glomerulonephritis
- hypersensitivity reactions
tissue destruction is caused by:
(give examples)
- a wide variety of chemicals (lead, mercury)
- drugs (lithium)
- venoms
what are some examples of metabolic disorders associated with pathologic neutrophilia?
what do they do?
- diabetes
- renal dysfunction/ liver disease
- produce circulating toxic substances that stimulate a neutrophilic response
what are some examples of malignant neoplasms?
- rapidly growing neoplasms
- some leukemias, such as:
* chronic myeloid leukemia (CML)
* chronic neutrophilic leukemia (CNL)
in hereditary neutrophilia, neutrophil counts are only mildly increased
(T/F)
false, mildly to markedly increased neutrophil counts
when the infection or inflammation is over, the____ returns to _____ over the period of ______.
- marrow proliferative activity
- baseline
- few days
patients with neutropenia are more susceptible to:
- bacterial or fungal infections
- without medical attention, condition may become life-threatening and deadly (neutropenic sepsis)
what is the most common cause of leukopenia?
neutropenia
neutrophil count in neutropenia is:
<1800/mm^3
causes of neutropenia are divided into 2 groups, what are they?
- decreased neutrophil production by the BM
- increased destruction/utilization of neutrophils elsewhere in the body
decreased neutrophil production by the BM is due to:
(briefly)
- aplastic anemia
- cancer, particularly blood cancer
- vitamin B12 or folate deficiency
- infections
what is aplastic anemia?
- destruction or injury to the BM
- results in hypoplastic or aplastic marrow (few BM cells)
- associated with decrease in all cell types
agents capable of causing marrow suppression (aplastic marrow) include:
- ionizing radiation
- chemicals
- cytotoxic drugs (used in the treatment of malignancy that destroy or interfere with the mitosis of proliferating cells)
- certain drugs
how does cancer decrease neutrophil production by BM?
- marrow replacement by tumors, leukemic cell, or fibrous tissue
- result in pancytopenia
how does vitamin B12 or folate deficiency decrease neutrophil production by BM?
- affects all highly dividing cells of the body including all blood elements
- causes pancytopenia
how do infections decrease neutrophil production by the BM?
direct BM suppression by toxins derived from the infectious agent
increased neutrophil destruction/ utilization due to:
(briefly)
- infections
- immune reactions (isoimmune/allo-immune, autoimmune, drug induced)
- sequestration by the spleen
how do infections increase neutrophil destruction/ utilization?
- increased passage to the tissues or increased margination
- any infection that overwhelms the marrow’s capacity to produce adequate nb of neutrophils
- result in neutrophils being consumed or recruited to the tissues faster than they are released by the marrow
what is the isoimmune or allo-immune neonatal neutropenia?
- fetal-maternal incompatibility involving only the neutrophils
- results from transplacental transfer of maternal IgG antibodies directed against fetal neutrophils
- the first born child is commonly affected
in autoimmune neonatal neutropenia, the first child is commonly affected
(T/F)
false, isoimmune or allo-immune
what is autoimmune neutropenia?
- when the body identifies neutrophils as enemies and makes antibodies to destroy them
- most common in infants and children
acquired autoimmune neutropenia has been described and is analogous to autoimmune hemolytic anemia and as common
(T/F)
false, not as common
drug induced neutropenia is associated with:
the use of a wide variety of drugs
sequestration by the spleen key points
- sequestration or trapping by the spleen
- splenic enlargement may lead to neutropenia
- relatively mild
what are the treatments of neutropenia?
(in details)
- corticosteroids (reduce antibody production)
- antibiotics (prevent infection)
- colony-stimulating factors: G-CSF or GM-CSF
- BM transplantation in severe cases
in eosinophilia, the eosinophil count exceeds:
700/mm^3
what are the main causes of eosinophilia?
- parasitic infestation (parasites that have a tissue cycle)
- allergic reactions (asthma, eczema)
- certain cancers or leukemias
- disorder called hypereosinophilic syndrome
what is the hypereosinophilic syndrome?
- disease characterized by a persistently elevated eosinophil count (>1500/mm^3)
- for at least 6 months
- no recognizable cause
in basophilia, basophilic count is above:
200/mm^3
what are the main causes of basophilia?
- allergic reactions
- cancers (MPD, CML)
what is the lymphocyte counts in lymphocytosis in:
* adults
* children
* infants
- adults: >4000 per microliter
- children: >7000 per microliter
- infants: >9000 per microliter
lymphocytosis is associated with what type of conditions or disorders in each of:
* children
* elderly
in children:
* a feature of infection
in elderly:
* lymphoproliferative diorders (chronic lymphocytic leukemia, lymphomas)
* lymphadenopathy
what are the causes of lymphocytosis?
- acute bacterial infections
- chronic bacterial infections
- parasitic infections
- viral infections
- lymphoproliferative diorders (CLL)
Viral infections tend to raise lymphocyte count but there are 2 special conditions where the lymphocyte count becomes very important:
(name them only)
- infectious lymphocytosis
- infectious mononucleosis
what is the infectious lymphocytosis?
- viral disease of children (1-10 years)
- small lymphocytes increase very much
- count can become very high
- yet all lymphocytes appear normal
what is the infectious mononucleosis?
- viral infection
- PB contains a micture of normal lymphocytes + atypical lymphocytes + increased nb of monocytes
- increased WBC count (12,000-15,000/mm^3)
monocyte count in monocytosis is above:
900/mm^3
monocytosis often occurs in what condition:
(general)
chronic inflammation
monocytosis is encountered in several conditions, what are they?
- tuberculosis & brucellosis
- bacterial infections
- inflammatory diseases
- parasitic infections
- rickettsial diseases
- fever of unknown origin
- recovering phase of acute bacterial infections
- infectious mononucleosis
- malignancy (leukemia)
