Leukocyte Disorders - Al-Mustansiriya University...•Serum –Blood that is allowed to stand clots...

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Leukocyte Disorders Dr Alauldeen Mudhafar Zubair

Transcript of Leukocyte Disorders - Al-Mustansiriya University...•Serum –Blood that is allowed to stand clots...

Page 1: Leukocyte Disorders - Al-Mustansiriya University...•Serum –Blood that is allowed to stand clots –Clot is a tangle of the “formed elements”(some are not truly cells) •RBCs

Leukocyte Disorders

Dr Alauldeen Mudhafar Zubair

Page 2: Leukocyte Disorders - Al-Mustansiriya University...•Serum –Blood that is allowed to stand clots –Clot is a tangle of the “formed elements”(some are not truly cells) •RBCs

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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Page 5: Leukocyte Disorders - Al-Mustansiriya University...•Serum –Blood that is allowed to stand clots –Clot is a tangle of the “formed elements”(some are not truly cells) •RBCs

• 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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Page 6: Leukocyte Disorders - Al-Mustansiriya University...•Serum –Blood that is allowed to stand clots –Clot is a tangle of the “formed elements”(some are not truly cells) •RBCs

• Blood is examined in a “smear”

• Smears are stained

Scanning EM

Light microscope

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Page 7: Leukocyte Disorders - Al-Mustansiriya University...•Serum –Blood that is allowed to stand clots –Clot is a tangle of the “formed elements”(some are not truly cells) •RBCs

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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Page 9: Leukocyte Disorders - Al-Mustansiriya University...•Serum –Blood that is allowed to stand clots –Clot is a tangle of the “formed elements”(some are not truly cells) •RBCs

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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Page 10: Leukocyte Disorders - Al-Mustansiriya University...•Serum –Blood that is allowed to stand clots –Clot is a tangle of the “formed elements”(some are not truly cells) •RBCs

• 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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Page 11: Leukocyte Disorders - Al-Mustansiriya University...•Serum –Blood that is allowed to stand clots –Clot is a tangle of the “formed elements”(some are not truly cells) •RBCs

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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Page 18: Leukocyte Disorders - Al-Mustansiriya University...•Serum –Blood that is allowed to stand clots –Clot is a tangle of the “formed elements”(some are not truly cells) •RBCs

Leukocytes

AKA WBCs: white blood cells

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Page 19: Leukocyte Disorders - Al-Mustansiriya University...•Serum –Blood that is allowed to stand clots –Clot is a tangle of the “formed elements”(some are not truly cells) •RBCs

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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Page 20: Leukocyte Disorders - Al-Mustansiriya University...•Serum –Blood that is allowed to stand clots –Clot is a tangle of the “formed elements”(some are not truly cells) •RBCs

• 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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Page 21: Leukocyte Disorders - Al-Mustansiriya University...•Serum –Blood that is allowed to stand clots –Clot is a tangle of the “formed elements”(some are not truly cells) •RBCs

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

Page 22: Leukocyte Disorders - Al-Mustansiriya University...•Serum –Blood that is allowed to stand clots –Clot is a tangle of the “formed elements”(some are not truly cells) •RBCs

All arise from stem cells

All originate in the bone marrow

Not shown are mast cells,osteoclasts, dendritic cells

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Page 23: Leukocyte Disorders - Al-Mustansiriya University...•Serum –Blood that is allowed to stand clots –Clot is a tangle of the “formed elements”(some are not truly cells) •RBCs

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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Page 25: Leukocyte Disorders - Al-Mustansiriya University...•Serum –Blood that is allowed to stand clots –Clot is a tangle of the “formed elements”(some are not truly cells) •RBCs

Eosinophils

• 1-4 % of leukocytes

• Bilobed

• Granules have digestive enzymes

• Role in ending allergic reactions and in fighting parasitic infections

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Page 27: Leukocyte Disorders - Al-Mustansiriya University...•Serum –Blood that is allowed to stand clots –Clot is a tangle of the “formed elements”(some are not truly cells) •RBCs

Basophils

• Rarest WBC

• Bilobed nucleus

• Dark purple granules

• Later stages of reaction to allergies and parasitic infections

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Page 29: Leukocyte Disorders - Al-Mustansiriya University...•Serum –Blood that is allowed to stand clots –Clot is a tangle of the “formed elements”(some are not truly cells) •RBCs

Lymphocytes*

• Most important WBC

• 20-45%

• Most are enmeshed in lymphoid connective tissue, e.g. lymph nodes, tonsils, spleen

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Page 31: Leukocyte Disorders - Al-Mustansiriya University...•Serum –Blood that is allowed to stand clots –Clot is a tangle of the “formed elements”(some are not truly cells) •RBCs

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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Page 32: Leukocyte Disorders - Al-Mustansiriya University...•Serum –Blood that is allowed to stand clots –Clot is a tangle of the “formed elements”(some are not truly cells) •RBCs

T cells attack foreign cells directly

• Killer cells (“cytotoxic”), or CD8+ is a main type

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Page 34: Leukocyte Disorders - Al-Mustansiriya University...•Serum –Blood that is allowed to stand clots –Clot is a tangle of the “formed elements”(some are not truly cells) •RBCs

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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Page 36: Leukocyte Disorders - Al-Mustansiriya University...•Serum –Blood that is allowed to stand clots –Clot is a tangle of the “formed elements”(some are not truly cells) •RBCs

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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Page 40: Leukocyte Disorders - Al-Mustansiriya University...•Serum –Blood that is allowed to stand clots –Clot is a tangle of the “formed elements”(some are not truly cells) •RBCs

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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Page 41: Leukocyte Disorders - Al-Mustansiriya University...•Serum –Blood that is allowed to stand clots –Clot is a tangle of the “formed elements”(some are not truly cells) •RBCs

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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Page 44: Leukocyte Disorders - Al-Mustansiriya University...•Serum –Blood that is allowed to stand clots –Clot is a tangle of the “formed elements”(some are not truly cells) •RBCs

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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Page 45: Leukocyte Disorders - Al-Mustansiriya University...•Serum –Blood that is allowed to stand clots –Clot is a tangle of the “formed elements”(some are not truly cells) •RBCs

• 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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Page 46: Leukocyte Disorders - Al-Mustansiriya University...•Serum –Blood that is allowed to stand clots –Clot is a tangle of the “formed elements”(some are not truly cells) •RBCs

• 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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Page 47: Leukocyte Disorders - Al-Mustansiriya University...•Serum –Blood that is allowed to stand clots –Clot is a tangle of the “formed elements”(some are not truly cells) •RBCs

• 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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Page 51: Leukocyte Disorders - Al-Mustansiriya University...•Serum –Blood that is allowed to stand clots –Clot is a tangle of the “formed elements”(some are not truly cells) •RBCs

Classification of Leukocyte Disorders:

• Benign or Malignant

• Hereditary or Acquired

• Functional or Numerical

• Morphological

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Page 52: Leukocyte Disorders - Al-Mustansiriya University...•Serum –Blood that is allowed to stand clots –Clot is a tangle of the “formed elements”(some are not truly cells) •RBCs

Variations in Morphology

Congenital

• Barr bodies: Drumstick appendage in females, itrepresents inactive X chromosome.

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Page 53: Leukocyte Disorders - Al-Mustansiriya University...•Serum –Blood that is allowed to stand clots –Clot is a tangle of the “formed elements”(some are not truly cells) •RBCs

• Pelger Huet anomaly: bilobed neutrophil

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Page 54: Leukocyte Disorders - Al-Mustansiriya University...•Serum –Blood that is allowed to stand clots –Clot is a tangle of the “formed elements”(some are not truly cells) •RBCs

• Neutrophil Hypersegmentation: Autosomal Dominant

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Page 55: Leukocyte Disorders - Al-Mustansiriya University...•Serum –Blood that is allowed to stand clots –Clot is a tangle of the “formed elements”(some are not truly cells) •RBCs

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

Page 56: Leukocyte Disorders - Al-Mustansiriya University...•Serum –Blood that is allowed to stand clots –Clot is a tangle of the “formed elements”(some are not truly cells) •RBCs

Chediak-Higashi Syndrome

• Oculocutaneousalbinism– Photophobia

– Sun sensitivity

• Neuropathy

• Infections, esp Staph aureus

• TX: BMTW. B. Saunders Adv Neonatal Care

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Page 60: Leukocyte Disorders - Al-Mustansiriya University...•Serum –Blood that is allowed to stand clots –Clot is a tangle of the “formed elements”(some are not truly cells) •RBCs

Acquired

• Toxic Granulation: Infection

• Hypersegmented Neutrophils: megaloblastic

anemia, cytotoxic drugs

• Pseudo- Pelger Huet(acquired): in

myelodysplasia

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Page 62: Leukocyte Disorders - Al-Mustansiriya University...•Serum –Blood that is allowed to stand clots –Clot is a tangle of the “formed elements”(some are not truly cells) •RBCs

• 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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Page 63: Leukocyte Disorders - Al-Mustansiriya University...•Serum –Blood that is allowed to stand clots –Clot is a tangle of the “formed elements”(some are not truly cells) •RBCs

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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Page 66: Leukocyte Disorders - Al-Mustansiriya University...•Serum –Blood that is allowed to stand clots –Clot is a tangle of the “formed elements”(some are not truly cells) •RBCs

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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Page 68: Leukocyte Disorders - Al-Mustansiriya University...•Serum –Blood that is allowed to stand clots –Clot is a tangle of the “formed elements”(some are not truly cells) •RBCs

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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Page 71: Leukocyte Disorders - Al-Mustansiriya University...•Serum –Blood that is allowed to stand clots –Clot is a tangle of the “formed elements”(some are not truly cells) •RBCs

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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Page 72: Leukocyte Disorders - Al-Mustansiriya University...•Serum –Blood that is allowed to stand clots –Clot is a tangle of the “formed elements”(some are not truly cells) •RBCs

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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Page 76: Leukocyte Disorders - Al-Mustansiriya University...•Serum –Blood that is allowed to stand clots –Clot is a tangle of the “formed elements”(some are not truly cells) •RBCs

• 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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Page 79: Leukocyte Disorders - Al-Mustansiriya University...•Serum –Blood that is allowed to stand clots –Clot is a tangle of the “formed elements”(some are not truly cells) •RBCs

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