Pathology of Hematopoietic System

Dr. Bikash Puri

Erythrocytes Disorder

Erythrocytosis or Polycythemia

• It is an increase in erythrocytes number, haemoglobin concentration, and PCV.
• Two types:
• Relative polycythemia
• Absolute polycythemia
• Relative polycythemia:
• The haematocrit and erythrocytes and haematocrit number are increased but the total erythrocyte mass is normal.
• Occurs from dehydration or haemoconcentration

B. Absolute polycythemia:�

• It is an actual increase in erythrocyte number.
• Causes:
• Primary erythrocytosis: occurs from proliferation of marrow erythroid precursors. Not influenced by erythropoietin. Example: erythroid leukemia.
• Secondary erythropoietin: results from excessive production of erythpoietin. Occurs in response to hypoxia. Example: Altitude sickness, pulmonary emphysema, heart diseases.

• Macroscopic findings:
• Dehydration…….mucus membrane dry and sticky.
• Cyanotic oral mucous membranes and depression
• Increased viscosity of blood. Increase haemoglobin concentration
• Microscopic findings:
• Increase no of erythrocytes.
• Hyperplasic bone marrow

Anemia

• Condition in which there is reduction in total number of red blood cells, PCV, hemoglobin concentration or all three.
• It is not a disease but rather a symptom of an underlying disease process.
• Clinical signs
• Pale mucous membranes
• Weakness or loss of stamina
• Tachycardia, heart murmur
• Shock if one-third of the blood volume is lost
• Icterus, hemoglobinuria, hemorrhage, edema or fever may be observed depending on the pathophysiologic mechanism involved.

Classification of anemia

CLASSIFICATION OF ANEMIA ACCORDING TO MORPHOLOGY

1. Red Blood Cell Size

A. MACROCYTIC (INCREASED MCV)

• Increase size of RBC or Increase MCV.
• Bone marrow is responsive. Presence of large no. of immature RBC in (reticulocytes and nucleated red cells), which are larger, into the peripheral blood. e.g. Blood loss or hemolysis, B12, folic acid deficiency.

B. NORMOCYTIC (Normal MCV)

• Normal size of RBC.
• There is interference with erythropoiesis at the stem cell level resulting in fewer cells entering the maturation process. Those that do enter the process develop normally and are released at the normal time. e.g. Aplastic anemia

C. MICROCYTIC (Reduced MCV)

• Smaller size of RBC.
• This is the type seen in iron deficiency anemia.

2. HEMOGLOBIN CONCENTRATION�

A. HYPERCHROMIC

• Elevated Hemoglobin concentration
• may indicate free hemoglobin in the plasma due to hemolysis, Heinz bodies in RBCs, or to excessive amounts of EDTA which cause shrinkage of RBCs.

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B. Normochromic

• Normal Hb concentration

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C. Hypochromic

• Reduced Hb concentration
• Example: Deficiency anemias, and in blood loss and hemolysis where the number of immature cells greatly exceeds the number of mature red blood cells.

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CLASSIFICATION OF ANEMIA ACCORDING TO RESPONSE�

A. REGENERATIVE

• Bone marrow is responsive to anemia
• Characterized by increase production of large no. of immature RBC in peripherial
• Example: blood loss and hemolytic anemias.
• Signs of increased erythrocyte production by the bone marrow may include:
• Reticulocytosis
• Polychromasia
• Basophilic stippling
• Anisocytosis
• Nucleated red cells
• Howell-jolly bodies
• NON-REGENERATIVE
• Bone marrow is not responsive to the anemic state.
• inability of the marrow to produce red blood cells
• Example: Depression anemias and aplastic anemias.

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Classification of anemia based on Pathophysiologic mechanism

1. Blood loss anemia:
• Occurs when 25-40% of the circulating blood volume is lost.
• In case of severe blood loss it lead to depletation of iron leading to hyopchromic , macrocytic anemia.

Causes:

• Trauma
• Surgery
• Vascular neoplasm
• Coagulation defects
• Sever Parasitism
• G.I Ulceration

Findings:

• Initially, animal may be in shock due to blood loss (Hypovolemic shock)
• There is decrease in RBC, Hb and PCV.
• Bone marrow responsive to anemia which is characterized by polychromasia, nucleated red blood cels and reticuloctosis.
• Leukocytosis with left shift is evident.
• Hypoproteinemia often complicates the anemia.

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2. Hemolytic anemia

• Results due to accelerated erythrocytes destruction
• Characterized by macrocytic hypochromic anemia.

Causes:

• Intrinsic: Abnormal hemoglobin; RBC enzymes deficiencies (PK deficiency); Membrane abnormalities. Autoimmune reaction.
• Extrinsic: Example- antibodies, toxins, parasites, chemicals and mechanical

Findings:

• Pale mucus membrane
• Blood is thin and watery
• Hemoglobinemia and Hemoglobinurea is evident.
• Spleenomegaly,
• Decrease number of erythrocytes,
• Hemosidrin laden cells in spleen
• Presence of nucleated RBC in blood in lateral stages.
• Signs of bone marrow response in later cases
• Neutrophilic leukocytosis, eosinnopenia and lymphopenia

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3. Reduced or Defective Erythropoiesis

1. Depression Anemia
• Occurs due to selective depression of erythropoiesis.
• Characterized by normocytic normochromic anemia.
• Bone marrow is non responsive to anemia.

Causes:

• Chronic inflammatory disease
• Chronic renal disease
• Neoplastic diseae
• Endocrine disturbances: example- hypopituitarism, hypothyroidism
• Parasitic infestation: example- Trichostrongylosis of cattle.

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B. Aplastic anemia

• Results due to damage in multipotential stem cell.
• It is a normocytic, normochromic, non regenerative anemia.
• Causes:
• Irradiation
• Bracken fern poisoning
• Chemicals- insecticides, chloramphenicol, sulfonamides, alkylating agents, etc.
• Neoplasia of bone marrow.

Deficiency Anemia

Causes:

• Deficiency of Vitamins: example- Vit-B12, folic acid, etc
• Deficiency of Minerals: examples- Iron, Copper, Cobalt etc.
• Sever parasitism.

Findings:

• Deficiency of vit. B12 leads to pernicious anemia, a macrocytic anemia associated with leukopenia and thrombocytopenia.
• Iron deficiency leads to microcytic, hypochromic anemia
• Poikilocytosis is common
• Erythroid hyperplasia in marrow.
• Regenerative signs of anemia is evident

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Leukocytes disorder

• Leucocytosis
• It is increase in number of WBC in circulating blood
• As the leucocytes consist of neutrophil, eosinophils, basophils, monocytes and lymphocytes; the increase in number of --------
• Neutrophils………….is termed as neutrophilia,
• Eosinophils…………. As eosinophilia
• Basophils…………… as basophilia
• Monocytes…………. . as monocytosis.

Causes: �

• Neutophilia: Bacterial infection; Stress reaction, Massive area of necrosis, Granulocytic leukemia, stress reaction, malignancy, chemical intoxication, Severe internal hemorrhage, hemolysis of rbcs, etc.
• Eosinophilia: Parasitism, allergy, decomposition of body protein, eosinophilic myositis, eosinophilic enteritis, adernal insufficiency.
• Basophilia: allergies
• Monocytosis: stress and chronic inflammatory lesions associated with bacteremia.
• Lymphocytosis: Inflammation of lymphatic tissues, lymphatic leukemaia, viral infection..

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Macroscopic features

• No characteristic lesion.

• Reactive lymph node hyperplasia.

• Enlargement of lymphoid organs such as spleen, thymus and bursa.

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Microscopic features

• Increase in number of total leucocytes in blood.

• Increase in absolute lymphocyte, absolute neutrophil, absolute eosinophil counts.

• Hyperplastic lesions in lymphoid organs.

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Response of leukocytes

• Injury of tissue or cells >> release of chemical substances >>initiate the inflammatory reaction >> migration of neutrophils into the area of injury via chemotaxis
• Similarly, the leukocytosis promoting factor produced from injured cell is carried to bone marro via blood >> this stimulates granulopoiesis>> this increase the supply of neutrophils in initial stages.
• Mature neutrophils are preferentially released from the maturation and storage pool into the peripheral blood.
• But severe inflammatory response, the need for neutrophil is large and immediate.
• When the need for neutrophils exceeds the ability of bone marrow to supply that need in the form of mature neutrophils, then immature neutophils are released to peripheral blood.
• Thus, the intensity of a disease process may be gauged by the extent of the shift to the left. 

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CLASSIFICATION OF THE LEUKOCYTE RESPONSE

REGENERATIVE LEFT SHIFT

• Characterized by a leukocytosis due to a neutrophilia with the appearance of immature granulocytes in peripheral blood.

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DEGENERATIVE LEFT SHIFT

• The total leukocyte count remains in the normal range or is only slightly elevated, while the immature granulocytes are markedly increased.
• It reflects the inability of the bone marrow to response to the infection.
• It is commonly seen in bacterial infection with septicemia.

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Leukaemoid Reactions

• The leukocyte count usually rises to 15,000 or 20,000 cells per µL (normal = 4000 to 10,000 cells per µL),
• But sometimes may rise to as high as 40,000 to 100,000 cells per µL. These extreme elevations are referred to as leukaemoid reactions,

Leucopenia

• Decrease in number of white blood cells.
• If there is decrease in number of all 5 cells of leucocytes it is called panleucopenia.
• Decrease in number of neutrophils is termed as neutropenia.
• Decrease in number of lymphocytes as lymphopenia.

Etiology;

• Congenital e.g: Chidiak-Higashi syndorme
• Infections: e.g: Feline panleucopenia virus, IBD, etc
• Chemicals: e. g: Pesticides and heavy metals
• Radiation : e.g: X-ray.

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Macroscopic findings

• Atrophy of lymphoid organs
• Recurrent infection, vaccination failure, pyogenic disorders
• Oedema, haemorrhage in bursa, or atrophy of bursa in IBD.

Microscopic findings:

• Decrease in total leucocytes and absolute neutrophil and absolute lymphocyte counts.
• Degeneration and necrosis of lymphoid cells in follicles of lymphoid organ
• Oedema, necrosis, proliferation of fibrous tissue in bursa in IBD

Thrombocytosis

• It is an increase in the number of blood platelets.
• Platelets number fluctuate in the blood of animals and increase greatly in response to most haemopoietic stimuli
• Neutrophilia and anemia with reticulocytosis are usually accompanied by thrombocytosis.

Thrombocytopaenia

• It is a decrease in the number of blood platelets.
• Occurs due to premature cellular destruction or defective production
• Causes: DIC, Erlichiosis, endothelial injuries, Blacken fern poisoning in cattle.

Spleenitis

• It is the inflammation of spleen
• Characterized by enlargement of spleen.
• Etiology:
• Infections: bacteria, virus
• Deficiency of vitamins and minerals
• Amyloidosis
• Immunodeficiency e.g: enviromental pollution
• Macroscopic findings:
• Enlargement of spleen
• Necrotic patches on spleen
• In chronic cases: Atrophy and fibrosis of spleen
• Necrotic patches and congestion leads to mottling.

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Microscopic findings

• Congestion in spleen
• Proliferation of lymphoid follicels
• Oedema
• Proliferation of fibrous connective tissue
• Depletion of lymphoid cells/ follicles.

Lymphadenitis

• It is the inflammation of lymphnodes
• Etiology:
• Infections: e.g- rinderpest
• Immunological disorders e.g- immuno deficiency
• Deficiency: e.g- Deficiency of protein
• Enviromental pollution: e.g- pesticides
• Tumors e.g: lymphosarcoma

Macroscopic features

• Enlargement of lymph nodes
• Congestion, oedema of lymph node
• In chronic case- fibrosis and atrophy of lymph node.

Microscopic findings

• Congestion, edema, proliferation of lymphoid cells
• In chronic cases, proliferation of fibrous tissue, depletion of lmphoid cells.