Wbc Disorders

White Cells Disorders

Dr. Mehzabin Ahmed

Classification 

Disorders of white blood cells can be classified into two broad categories: 

Leukocytosis (Proliferative disorders)- in which there is an increase in numbers of leukocytes

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Leukopenia - in which there is a decreased number of leukocytes

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Proliferations of white cells can be reactive or neoplastic.

White Blood Cell Count WBC = 4-10,000/mm3 (normal)

Leukopenia 

This is a reduction in the number of Total WBCs less than normal in the peripheral blood

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Leukopenia could be due to Neutropenia, Lymphopenia or both

Neutropenia 

reduction in number of neutrophils below normal

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It may be due to:

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Reduced production of neutrophils

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Accelerated removal of neutrophils from the circulating blood

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Altered distribution of Neutrophils (Drugs, stress)

A fall in neutrophil counts below 500/mL is called Agranulocytosis

1-Decreased Production 

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Suppression of myeloid stem cells, as occurs in: 

Aplastic anaemia

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Infiltrative marrow disorders (tumors, granulomatous disease, etc.)

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Exposure to certain drugs ( Cytotoxic drugs, chemotherapy)

Ineffective granulopoiesis in disease states such as: 

Megaloblastic anaemias due to vitamin B12 or Folate deficiency and where defective precursors are susceptible to death in the marrow

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Myelodysplastic syndromes.

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Pure WBC aplasia

2-Accelerated removal or destruction of Neutrophils  

Immunologically mediated injury to neutrophils Associated with immunologic disorders, eg/ SLE, Feltys syndrome

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Hypersplenism: in which excessive destruction occurs secondary to enlargement of the spleen, usually associated with increased destruction of red cells and platelets as well.

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Increased peripheral utilization -as may occur in overwhelming bacterial, fungal, or rickettsial infections

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Drug induced

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Complement mediated destruction-Hemodialysis -Cardiopulmonary bypass

Lymphopenia Lymphopenia is a reduction in the Lymphocyte count below normal Causes 

Primary Lymphopenia: 

Primary immunodeficiency diseases 

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Eg: Severe combined immunodeficiency

Secondary Lymphopenia: many causes 

Infections: Influenza, Miliary Tb, Malaria, HIV

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Loss of Lymphocytes: Whipples disease, severe Right side Heart failure, Lymphatic fistula

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Drugs: Radiotherapy, Corticosteroids, Cytotoxic drugs

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Neoplastic conditions: Metastatic CA, advanced Hodgkin’s disease

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Nutritional/Metabolic: B12/ Folate deficiency, Uremia

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Others: SLE, Aplastic anemia, Graft v Host disease, Sarcoidosis,

Neutrophilic Leucocytosis Neutrophilia is the increase in the Neutrophil count above 7.5×109 Causes of Neutrophilia 1-Bacterial infections: Pyogenic infections 2-Inflammation and Tissue necrosis: cardiac infarction, trauma, vasculitis 3-Metabolic disorders: uremia, eclampsia, acidosis, gout 4-Neoplasms: CA, Lymphoma, Melanoma 5-Acute hemorrhage or hemolysis 6-Corticosteroid therapy (inhibits margination) 7-Myeloproliferative diseases: CML, PRV 8-Treatment with myeloid growth factors: G-CSF, GM-CSF

White Blood Cells ●

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Leucocytosis - WBC count ●

Granulocytosis

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Lymphocytosis

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Monocytosis

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Eosinophilia,

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Basophilia

Leukopenia - WBC count ●

Neutropenia,

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Lymphopenia

Agranulocytosis -

500 mm3

Granulocytosis (Neutrophilia)

Neutrophilia may be accompanied by fever due to the release of Leukocyte pyrogens

Reactive Neutrophilia

Characteristic features of Reactive Neutrophilia 

Shift to the left in the peripheral blood differential WBC count (increase in the number of band forms, myelocytes, metamyelocytes)

Reactive changes in neutrophils

Toxic granulations

Dohle Bodies

1.Toxic granulations- coarse dark cytoplasmic granules 2. Dohle Bodies- blue cytoplasmic patches of dilated endoplasmic reticulum (arrow)

Activated neutrophils show increased alkaline phosphatase activity and give rise to Increased NAP scores

Lymphocytosis - causes ●

Most often viral infection

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Chronic inflammation

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Marked lymphocytosis with activated lymphocytes – seen in infectious mononucleosis (EBV)

Lymphocytes - Normal

Lymphocytosis

Monocytosis Causes of Monocytosis include: ●

Chronic bacterial infections -bacterial endocarditis, malaria, Tb, Typhoid

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Chronic inflammation- Collagen vascular diseases, SLE, RA, ulcerative colitis, Sarcoidosis

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Malignant- AML, CA, MDS, Hodgkins disease

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Others- post splenectomy, chronic neutropaenia

Eosinophilia Causes of Eosinophilia include: ●

Allergic disorders: hay fever, Bronchial asthma, urticaria, food hypersensitivity

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Skin disease: Psoriasis, Pemphigus

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Parasitic infestations: Amoebiasis, Ascariasis, Hookworm, Filariasis

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Pulmonary eosinophilia and the Hypereosinophilic syndrome

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Drug sensitivity

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Hodgkins disease

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Metastatic malignancy with tumor necrosis

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Eosinophilic leukaemia

Basophilia ●

Basophilia occurs in Myeloproliferative disorders (CML)

Leukaemoid Reaction This is a reactive and excessive leucocytosis, characterized by:  WBC counts up to 15 - 100,000/mm3  Shift to the left (immature WBCs)  Signs of activation Dohle bodies, toxic granulations (Differs the condition from CML)  NAP scores high (Differs the condition from CML)  MPO negative (Myeloperoxidase) - reverse of CML  Underlying disease: Severe or chronic infections Severe haemolysis Metastatic CA  Leukamoid reactions are particularly marked in children

Leukaemoid Reaction

LAP +ve

MPO +ve in CML

“Shift to the Left”

Malignancies of the leukocytes

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LEUKAEMIA 

it is the malignant proliferation of the WBC, with the presence of the immature forms in the peripheral circulation

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MYELOMA 

it is the malignant proliferation of the plasma cells, the immunoglobulin producing cells.

LEUKEMIA 

Definition 

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Leukemia is a type of cancer. It is the cancer of the blood cells.

Leukemia When leukemia develops, the body produces large numbers of abnormal blood cells. In most types of leukemia, the abnormal cells are white blood cells. The leukemia cells usually look different from normal blood cells, and they do not function properly.

Causes of leukemia 

Leukemia occurs more often in males than in females and

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In white people more often than in black people.

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Certain risk factors increase a person's chance of developing leukemia. For example, 

Exposure to large amounts of high-energy radiation.

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Exposure to electromagnetic fields is a possible risk factor (Electromagnetic fields are a type of low-energy radiation that comes from power lines and electric appliances.)

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Certain genetic conditions can increase the risk for leukemia. One such condition is Down's syndrome. Children born with this syndrome are more likely to get leukemia than other children.

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Workers exposed to certain chemicals over a long period of time. Benzene is one of these chemicals.

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Anti cancer drugs

Types of leukemia

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There are several types of leukemia.

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They are grouped in two ways. 

Acute vs Chronic

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Lymphoid vs Myeloid

ACUTE & CHRONIC 

Based on how quickly the disease develops and gets worse

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In acute leukemia,

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the abnormal blood cells are blasts that remain very immature

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cannot carry out their normal functions.

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The number of blasts increases rapidly, and

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the disease becomes worse quickly.

In chronic leukemia, 

some blast cells are present, but in general, these cells are more mature

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can carry out some of their normal functions.

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the number of blasts increases less rapidly than in acute leukemia, thus

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chronic leukemia worsens gradually.

LYMPHOID & MYELOID    

Based on the type of blood cell that is affected. lymphoid cells, - lymphocytic leukemia. myeloid cells - myeloid or myelogenous leukemia. These are the most common types of leukemia:  Acute lymphocytic leukemia (ALL)  is the most common type of leukemia in young children.  This disease also affects adults, especially those age 65 and older.  Acute myeloid leukemia (AML)  occurs in both adults and children.  This type of leukemia is sometimes called acute non-lymphocytic leukemia (ANLL).  Chronic lymphocytic leukemia (CLL)  most often affects adults over the age of 55.  It sometimes occurs in younger adults, but it almost never affects children.  Chronic myeloid leukemia (CML)  occurs mainly in adults.  A very small number of children also develop this disease.

Symptoms of leukemia 

Infections and fevers as leukemia cells are abnormal cells that cannot help the body fight infections.

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People with leukemia often have anemia and there are not enough red blood cells to carry oxygen through the body. The patients look pale and feel weak and tired.

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A decreased count of platelets (thrombocytopenia), causes the patients to bleed and bruise easily.

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In acute leukemia, symptoms appear and worsen quickly.

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In chronic leukemia, symptoms may not appear for a long time. When symptoms do appear, they generally are mild at first and get worse gradually.

Symptoms of leukemia (contd) 

These are some of the common symptoms of leukemia: 

Fever, chills, and other flu-like symptoms;

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Frequent infections;

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Swollen or tender lymph nodes, liver, or spleen;

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Weakness and fatigue;

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Loss of appetite and/or weight;

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Easy bleeding or bruising;

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Tiny red spots (called petechiae) under the skin;

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Swollen or bleeding gums;

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Sweating, especially at night; and/or

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Bone or joint pain.

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In acute leukemia 

The abnormal cells can collect in the brain or spinal cord (also called the central nervous system or CNS). 

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headaches, vomiting, confusion, loss of muscle control, and seizures.

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Leukemia cells also can collect in the testicles and cause swelling.

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Some patients develop sores in the eyes or on the skin.

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Leukemia also can affect the digestive tract, kidneys, lungs, or other parts of the body.

In chronic leukemia 

The abnormal blood cells may gradually collect in various parts of the body.

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Chronic leukemia can affect the skin, central nervous system, digestive tract, kidneys, and testicles.

WBC Disorders At the end of the lesson on WBC Disorders, the student should be able to:  Define terms – Leucocytosis, Leucopenia, leukemia, myeloma.  Enumerate the common causes of neutrophilia, eosinophilia & lymphocytosis.  Classify leukemia.  List the clinical manifestation of acute leukemia