Leukocyte Disorders - Al-Mustansiriya University...•Serum –Blood that is allowed to stand clots...
Transcript of Leukocyte Disorders - Al-Mustansiriya University...•Serum –Blood that is allowed to stand clots...
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Leukocyte Disorders
Dr Alauldeen Mudhafar Zubair
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Composition of blood• Specialized connective tissue
• Blood cells (formed elements) suspended in plasma
• Blood volume: 5-6 liters (approx 1.5 gal) in males and 4-5 liters in females
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Blood• Centrifuged (spun) to separate• Clinically important hematocrit
– % of blood volume consisting of erythrocytes (red blood cells)
– Male average 47; female average 42
• Plasma at top: water with many ions, molecules, and 3 types of important proteins:– Albumin– Globulins– Fibrinogen
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• Serum– Blood that is allowed to stand clots
– Clot is a tangle of the “formed elements” (some are not truly cells)• RBCs lack nuclei and organelles
• Platelets are fragments
• Most cannot divide
– Clear fluid serum is left = plasma without the clotting factors
When spun in centrifuge, buffy coat lies between RBCs and plasma: of leukocytes (white blood cells) and platelets
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• Blood is examined in a “smear”
• Smears are stained
Scanning EM
Light microscope
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Hematopoiesis• Formation of blood cells
• Occurs mostly in red bone marrow
• All cells arise from same blood stem cell (pluripotent hematopoietic stem cells)
• Recently some have been found in adults which are mesenchymal stem cells, which can also form fat cells, osteoblasts, chondrocytes, fibroblasts and muscle cells
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Blood stem cells divide into:1.myeloid stem cells or2.lymphoid stem cells
All except for lymphocytes arise from myeloid stem cells
All originate in the bone marrow
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• As the cells divide they become “committed,”that is, they can only become one kind of cell
• Also called CFU’s (colony-forming units)
• Structural differentiation occurs
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CBC is probably commonest test done(“complete blood count”-how much of each type of cell)• Hemoglobin (gm/dl) usually
15
• Hematocrit (%)
• RBC count
• WBC in thousands/cumm– Differential if ordered: broken
down to amount of each type WBC
• Platelet count in thousands/cumm
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Leukocytes
AKA WBCs: white blood cells
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Leukocytes
AKA WBCs: white blood cells
Are complete cellsFunction outside the
blood
Note the size difference compared to erythrocytes
neutrophil eosinophil
basophil
small lymphocyte monocyte
__RBC
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• Granulolcytes, which include three types of
cells: neutrophils, eosinophils & basophils;
together with monocyte comprise the
phagocytes. Normally only mature phagocytic
cells and lymphocytes are found in the
peripheral blood.
• Lymphocyte, their precursor cells and plasma
cells make up the immunocytes.
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Leukocyte types
• Artificial division into granulocytes and agranulocytes
• Granulocytes: neutrophils, eosinophils, basophils (according to how stain)– Granules
– Lobed nuclei
– All are phagocytic
• Agranulocytes: lymphocytes, monocytesDr. Alauldeen Mudhafar Zubair 21
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All arise from stem cells
All originate in the bone marrow
Not shown are mast cells,osteoclasts, dendritic cells
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Neutrophils• 60% of all WBCs
• Nuclei of 2-6 lobes
• Other names:
– Polymorphonuclear cells (PMNs, polys, segs)
– Granules have enzymes
– Can damage tissue if severe or prolonged
– Pus
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Eosinophils
• 1-4 % of leukocytes
• Bilobed
• Granules have digestive enzymes
• Role in ending allergic reactions and in fighting parasitic infections
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Basophils
• Rarest WBC
• Bilobed nucleus
• Dark purple granules
• Later stages of reaction to allergies and parasitic infections
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Lymphocytes*
• Most important WBC
• 20-45%
• Most are enmeshed in lymphoid connective tissue, e.g. lymph nodes, tonsils, spleen
*Dr. Alauldeen Mudhafar Zubair 29
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Lymphocytes:
Nucleus occupies most of the cell volumeResponse to antigens (foreign proteins or parts of cells) is specific.Two main types attack antigens in different ways:
T cells B cells
plus “natural killer cells”
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T cells attack foreign cells directly
• Killer cells (“cytotoxic”), or CD8+ is a main type
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B cells
• Differentiate into plasma cells
• Plasma cells secrete antibodies
• Antibodies flag cells for destruction by macrophages (see stem cell chart)
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Monocytes
• 4-8% of WBCs
• In connective tissue they transform into macrophages(phagocytic cells with pseudopods)
*Dr. Alauldeen Mudhafar Zubair 36
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Normal Values: for adult Caucasian
Total leukocytes 4.0-11.0 X 10 9/l
Neutrophils 2.5-7.5 X 10 9/l
Eosinophils 0.04- 0.4 X 10 9/l
Monocytes 0.2- 0.8 X 10 9/l
Basophils 0.01-0.1 X 10 9/l
Lymphocytes 1.5-3.5 X 10 9/l
Normal black and Middle Eastern subjects may have lower counts due to margination.
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Development in the bone marrow (14 days)
• Myeloblast Promyelocyte Myelocyte
Metamyelocyte BandNeutrophils.
• These stages are seen only in the bonemarrow in healthy people. However, theyappear in peripheral blood in pathologicalconditions.
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Granulopoiesis
• The blood granulocytes and monocytes are formed in the bone marrow from a common precursor cell.
• Large numbers of band and segmented neutrophils are held in the marrow as a ‘ reserve pool ’ or storage compartment.
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• The bone marrow normally contains more myeloid cells than erythroid cells.
• In the stable or normal state, the bone marrow storage compartment contains 10 –15 times the number of granulocytes found in the peripheral blood.
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• In the bloodstream there are two pools
usually of about equal size: the circulating
pool (included in the blood count) and the
marginating pool (not included in the blood
count).
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• Following their release from the bone marrow, granulocytes spend only 6 – 10 hours in the circulation before moving into the tissues where they perform their phagocytic function.
• They spend on average 4 – 5 days in the tissues before they are destroyed during defensive action or as the result of senescence.
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Classification of Leukocyte Disorders:
• Benign or Malignant
• Hereditary or Acquired
• Functional or Numerical
• Morphological
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Variations in Morphology
Congenital
• Barr bodies: Drumstick appendage in females, itrepresents inactive X chromosome.
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• Pelger Huet anomaly: bilobed neutrophil
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• Neutrophil Hypersegmentation: Autosomal Dominant
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Chediak-Higashi syndrome: is a rare autosomal
recessive disorder characterized by
oculocutaneous albinism, recurrent and severe
bacterial infections, giant blue-grey granules in
the cytoplasm of granulocytes, monocytes &
lymphocytes , a mild bleeding diathesis,
progressive peripheral neuropathy and cranial
nerve abnormalities.Dr. Alauldeen Mudhafar Zubair 55
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Chediak-Higashi Syndrome
• Oculocutaneousalbinism– Photophobia
– Sun sensitivity
• Neuropathy
• Infections, esp Staph aureus
• TX: BMTW. B. Saunders Adv Neonatal Care
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Acquired
• Toxic Granulation: Infection
• Hypersegmented Neutrophils: megaloblastic
anemia, cytotoxic drugs
• Pseudo- Pelger Huet(acquired): in
myelodysplasia
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• Shift to the left: increase in the number of
band forms and the occasional presence of
more primitive cells in the peripheral blood.
• Leukoerythroblastic picture: a presence of a
shift to left plus nucleated RBC in the
peripheral blood.
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Causes of leucoerythroblasticblood film
• Metastatic neoplasm in the marrow• Primary myelofi brosis• Acute and chronic myeloid leukaemia• Myeloma, lymphoma• Miliary tuberculosis• Severe megaloblastic anaemia• Severe hemolysis• Osteopetrosis
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The Leukomoid Reaction:
a reactive excessive leukocytosis with the presence ofimmature cells (myeloblasts, promyelocytes and myelocyte)in the peripheral blood.
In other words (leukocytosis + left shift). Usually it is aneutrophil leukocytosis. It can be lymphoid
Causes :
1. Severe infection
2. Severe haemolysis
3. Metastatic cancerDr. Alauldeen Mudhafar Zubair 66
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Variations in Number:
NeutrophiliaCauses are:
1. Infection (bacterial)
2. Inflammatory conditions
3. Neoplasia
4. Metabolic conditions
5. Hemorrhage, Hemolysis
6. MPD
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7. Drugs (e.g. corticosteroid therapy (inhibits
margination): lithium, tetracycline)
8. Treatment with myeloid growth factors (e.g. G -
CSF)
9. Rare inherited disorders
10. Asplenia
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Neutropenia• The lower limit of the normal neutrophil
count is 2.5 *10 9 /L except in black people
and in the Middle East where 1.5 *10 9 /L is
normal. When the absolute neutrophil level
falls below 0.5 *10 9 /L the patient is likely to
have recurrent infections
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NeutropeniaCauses are:1. Congenital (Kostmann’s syndrome)2. Cyclical neutropenia3. Marrow aplasia4. Megaloblastic anemia5. Infections (typhoid, miliary TB, viral hepatitis)6. Drugs7. Irradiation8. Immune disorders9. Hypersplenism
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EosinophiliaCauses are:
1. Parasitic infection
2. Skin disorders
3. Allergic conditions
4. Neoplasia
5. Myeloproliferative disorders
6. Hypereosinophilic syndrome
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Basophilia:
• An increase in blood basophils above 0.1 *10 9 /L is uncommon.
• The usual cause is a myeloproliferative disorder such as chronic myeloid leukemia or polycythaemia vera. Reactive basophil increases are sometimes seen in myxoedema, during smallpox or chickenpox infection and in ulcerative colitis.
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• Monocytosis: A rise in blood monocyte count above 0.8 *10 9 /L is infrequent.
Causes are:• Chronic bacterial infections: tuberculosis, brucellosis,
bacterial endocarditis, typhoid• Connective tissue diseases – SLE, temporal arteritis,
rheumatoid arthritis• Protozoan infections• Chronic neutropenia• Hodgkin lymphoma, AML and other malignancies• Chronic myelomonocytic leukemia
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Lymphocytosis
Causes are:1. Viral infections (infectious mononeuclosis, infectious
lymphocytosis, CMV …etc).
2. Bacterial infections: (Pertussis, occasionally healingTB, Brucellosis, Secondary and Congenital Syphilis,Typhoid fever, Diphtheria)
3. Protozoal infections: Toxoplasmosis
4. Lymphoproliferative Disorders: CLL, Lymphoma
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