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Viruses -Virus : obligate intracellular parasites . -Virus contain two genomes DNA or RNA But not both . which contain :- ss : single stranded . ds : double stranded -Capsid :- protein shell that enclose the viral genome . -Capsid symmetry : (( cabic – helical – complex )) -Viral Enveloped : help in infect host and composed of lipid bilayer and glycoprotein -Bacterophage :- viruses that infect bacteria cell ( prokaryotic ) -Virion :- complete virus particle : nuclic acid + protein . it is extracellular phase of virus (( before virus enter host cell )) -Vector virus passed from host to host through direct contact and vector . -Nucleocapsid :- viral nucleic acid + protein coat . -Viroids : is naked circular single strand RNA that infect plants . it is the smallest known pathogens . -Prions :- is infectious proteins cause brain disease e.g :- mad cow and CJD in human . -DNA viruses replicate in nucleus of host except " poxvirus " ...

Chapter 21in haematology (multiple myeloma and related disorder)summary -The term paraprotienaemia refers to the presnce of a monoclonal immunoglobulin band in serum and reflects the synthesis of immunoglobin from asingle clone of plasma cells. -Multiple myeloma is a tumour of plasma cekks that accumulate in the bone marrow, release a prarprotein and cause tissue damage. The disease has apeak incidence in the seventh decade . -Almost all cases of myeloma develop from a pre-existing mnonclonal gammopathy of undetermined sigificance (MGUS)in which there is low level paraprotien and no 1% of cases progress to myeloma each year. -A useful reminder for the spectrum of tissue damage in myeloma is CRAB- hypercalaemia,renal impairment,anaemia,bone disease. -in patient younger than 75 years myeloma is usually treated bu intensve chemotherapy followed by anautologous stem cell transplant using stem cells harvested from the patient. -In older patiet chemotherapy alone is u...

Chapter 20 in haematology (Non-Hodgkin lymphoma)summary -Non-Hodgkin lymphomas are a large group of clonal lymphiod tumours.Appromixately 85% are of B-cell origin and 15% derive from T or NK cells. -Their clinical prestation and natural history are more variable than hodgkin lymphoma and can vary from very indolent disease subtypes though to rapidly progressive subtypes that need urgent treatment . -For many years clinicans have divided lymphomas into lowgrade and high-grade disease. This is useful as low –grade disorder are typically slowly progressive,respond well to chemothrapy but are vary difficult to cure,whereas high-grade lymophomas are aggressive more often curable. -Investigation is with lymph node biopsy,blood tests and radiology. Immuohistochemistry of the lymph node is valuable and cytogenetic analysis is performed in may cases. -Clinial staging is performed as for hodgki lymphoma. -Treatment for NHL   are based on a variety of chemotherapy r...

Chapter 19 in haematology (Hodgkin lymphoma)summary -Lymphoma are a group of diseases caused by malignant lymphocytes that accumulation in lymph nodes and cause lymphoadenopathy. -The major subdivision of lymphomas ia into hodgkin and this is based on the presence of Reed-strenberg cells in hodgkin lymphoma. -Reed-strenberg cells are neoplastic B cells but most cells i the lymph node are reactive inflammatory cells. -The usual clinical presentation is with painless asymmetrical lymphadenopathy- most commonly in the neck. -Constitutional symptoms of fever,weight loss and sweating are prominent in patients with widespresd disease. -Blood tests may show anaemia, neutophilia and rasied erythrocyte sedmentation rate (ESR) or lactic dehydrogenase (LDH). -Diagnosis is made by histological examination of an excised lymph node and there are four subtype of disease . -Staging of the disease is important for determining treatment and prognosis history, examian...

  Chapter 18 in haematology (chroinc lymphoid leukaemias)summary -Chronic lymphocytic leukaemiaes are characterized by the accumulation of mature B or T lymphocytes in the blood. -Individual subtypes are distinguished on the basis of morphology,immunophenotype and cytogenetics. -Chronic lymphocytic leukaemia (CLL,B cell) represents 90% of cases and has a peak incidece between 60 and 80 years of age .There is genetic predisposition to development of the disease. -Most cases are indenified when a routine blood test is performed the patient can develope enlarged lymph nodes ,splenomegaly and hepatomegaly. -Immunosuppression is asignificant problem because of hypogammaglobuilaemia and cellular immune dysfunction. -Anaemia may also develop because of autoimmune haemolysis and bone marrow in filtration. -Diagnosis is usually performed by immuophenotypic analysis of peripheral blood which reveals aclonal population of CD5 + ,CD23 + B cells. -The best gu...

Chapter 17 in haematology (Acute lymphoblastic leukaemia)summary -Acute lymphoblastic leukaemia (ALL) is casued by an accumulation of lymphoblasts in the bone marrow. It isthe most common malignant disease of clidhood-75% of cases occur before the age of 6 years. Eighlty-five per cent of cases are of B-cell lineage with the rest being of T-cell lineage. -The first genetic mutation ocuurs in amy cases in utero , with a secondary genetic event occuring later inclidhood,possibly as a reaction to an infection. -The clinical presentation is with the features of bone marrow failure (anaemia,infection and bleeding) together with symptoms of tissue infiltration by tumour cells, leading to bone pain or swollen lymph nodes. -Diagnosis is by examination of blood and bone marrow.important tests include microscopic examination of the tumour cells, immunophenotyping and genetic analysis. -ALL is subclassified according to the underlying genetic defect and a wide varity of genet...

Chapter 16 in haematology (Myelodysplasia)summary -Myelodysplasia include a group of clonal disorders of heamopoietic stem cells that lead to bone marrow failure and low blood cell counts.Ahallmark of the disease is simultaneous proliferation and apoptosis is haemopoietic cells leading to the paradox of a hypercellular bone marrow but pancytopenia in peripheral blood . there is a tendency to progress to acute myeloid leukaemia. -In most cases, the disease is primary but it may be secondary to chemotherapy given for treatment of another malignancy. -The main clinical features of anaemia, infectionand bleeding, are caused by reduction in the bone count.most patients are over 70 years of age. -Diagnosis is made by examination of the blood and bone marrow together with genetic studies of the tumour cells . they are calssfiedinto eight major subtypes. -Scoring systems can divide patients in those with low-grade or high-grade disease . -Low-grade disease may not nee...

Chapter 15 in Haematology (myeloproliferative neoplasms) summary      The increase in blood viscosity leads to headaches,plethoric appearance and splenomegaly. -Treatment aims to maintain the haematocrit around 0.45. useful apporaches include venesection or hydroxyurea and aspirin is also given.JAK2 inhibitors are being assessed in clinical trials.survival is usually over 10 years but there may be progression to leukaemia or myelofibrosis. -Secondary polycythaemia can arise from rare congential causes or acquired disorder such as lung disease or tumours that secrete erythropoietin,venesection may be needed. -Essential thrombocythaemia is diagnosed by persistent raied platelet count in the absence of other causes.JKA2 is mutated in appromixtaley 50% of cases. -The predominant feature of primary myelofibrosis is a progressive generalized reactive fibrosis of the bone marrow in association with the developement of haemopoiesis in the spleen ...

Chapter 14 in Haematology (chronic myeloid leukaemia) summary            -Chronic myeloid leukaemia is a clonal disorder of a pluripotent steam cell. The disease accounts for around 15 %of leukamias and may occur at anu age. -All cases of CML have a transloction between chromosomes 9 and 22. This leads to the BCP hene on chrosome 22 and generates the philadelphia chromosome. -The resulting chimeric BCR-ABL1 gene codes for a fusion protien with tyrosine kinase activity. -In some patients the phildaelphia examination of tumour cells but the only be detected by FISH or PCR. -The disease can occur at any age but is most common between the ages of 40 and 60 years. -The clinical feauters include anaemia bleeding and splenomegaly. There is usually a marked neutrophlia with myelocytes and basophils seen in the blood film. -Transformation to an accelerated phase or acyte leukaemia may occur. -Treatement is with ty...

Chapter 13 in Haematology (Acute myeloid leukaemia) summary                     -The leukaemia are a groupof disorders characterized by the accumulation of malignant white cells in the bone marrow and blood . they can be classified into four subtypes on the basis of being either acute or chronic, and myeloid or lymphoid. -Acute leukaemia are aggressive diseases in which transformation of a haemopoietic stem cell leads to accumulation of >20% blast cells in the bone marrow. -The clinical feature of acute leukaemia result from bone marrow failure and include anaemia ,infection and bleeding. Tissue infiltration can also occur. -AML is rare i chlidhood but becomes increasingly common with age with a median onset of 65 years. -The diagnosis is made by analysis of blood and bone marrow using microscopic examination (morphology)as well as immunophenotypic, cytogenetic and...

Chapter 12 in Haematology (Haematoloical malignancy: managment) summary -Progress in the treatment of haemopoietic malignancies has been the result of improvemnets in both supportive therapy and speicific tumour treatments. -Supportive treatments often include : insertion of a central nevous catheter; Appropriate use of red cell and platelet transfusions; Early administration of drugs to traet infection;Otimiziation of the blood coagulation system Drugs to reduce side effects such as nausea or pain;Psychological support. -Gram-positive skin organisms such as staphyloccus are common infections and often colonize central venous catheters. -Gram-Negative bacteria are usually derived from the gut and and can cause severe septicemia. -The use of air filters,handwashing and antibiotics can reduce infection rates . -Neutropenic patients who developa fever should be treated urgently with broad-spectrum antibiotics. -Herpes viruses are a common cause of infection in ...

Chapter 11 in Haematology (Haematological malignancy:aetiology and genetics) summary   -The haemopoietic malignancies are clonal diseases that derive from a single cell in the marrow or peripheral lymphoid tissue which has undergone genetic alteration. -They represent approximately 7% of all mlignant disease. -inherited and envirmental factor both predispose to tumour development but the relative contribution of these is usually unclear. -infections (viral and bacterial),drugs, radiation and chemicals can all inrease the risk of developing a haemopoietic malignancy. -Haematological malignancies occur because of genetic alteration that lead to increased activation oncogenes or decreased activity of tumour suppressor genes. -These genetic alterations may occur through avarity of mechanisms such as point mutation, chromosomal, traslocation, or gene deletion . -Important investigation include study of the chromosomes (karyotype analysis),FISH,PCR, microta...

Chapter 9 in Haematology (White cells: lymphocytes) summary -Lymophcytes are immunologically comptent white cells that are involved in antibody production   (B cells) and with the body's defence against viral infection or other foreign invasion (T cells). -They arise from haemopoietic stem cells in the marrow, T cells being subseqently processed in the thymus. -B cells secrete gammaglobulin antibodies specific for individual antigens.T lymphocytes are further subdivided into helper (CD4 + ) and cytotoxic (CD8 + )cells .They recognise peptides on HLA atigens.Natural killer cells are cytoxic CD8 + cells that kill target cells with low expression of HLA molecules. -The immune response occurs in the germinal centre of lymph nodes and involves B-cell and T-cell proliferation, somatic mutation, selection od cells by recognition of antigen on antigen-presenting cells and formation of plasma cells (which secrete immunoglobulin)or memory B cells. -Immunoglobulins inc...

Chapter 10 in Haematology (spleen) summary - The normal dult spleen wight 150*250g and is 5-13 cm in diameter. It has a specialized circulation because the majority of arterioles end in "cords" which lack an endothelial lining. The blood re-entres the circulation via venous sinuses. The cords and sinuses form the red pulp which monitors the inegrity of red blood cells. -The central arterioles are surrounded by lynphoid tissue called white pulp which is similar in structure to a lymph node. -The spleen removes aged or abnormal red cells, and excess DNA ans siderotic granules, from intact red cells. It also has a specialized immune function against capsulated bacteria, pneumococcus,haemophilus influenza and meningococcus to which splenectomy is needed for splenic rupture and in some haematological diseases. -Enlargement of the spleen   (splenomegaly) occurs in many amlignant and benign haematologicaldiseases,in portal hypertension and with systemic diseases, i...

Chapter 8 in Haematology (Granulocytes and monocytes) summary -Granulocytes include neutrophils (polymorphs),eosinophils and basophils.They are made in the bone marrow under the control of a variety of growth factors   and have a short lifspan in the blood stream befor entring tissues. -Phagocytes (neutrophils and monocytes) are the   body's main defence against bacterial infection.Neutrophil leucocytosis occurs in bacterial infection and in other types of inflammation.Neutropenia , if severe, predisposes to infection. It may be caused by bone marrow failure, chemotherapy or radiotherapy drugs. -Eosinophilia is most frequently caused by allergic diseases, including skin diseases,parasitic infection or drugs. Ti can be caused by clonacal increase in eosinophils termed chronic eosinophil leukamia or an idiopathic condtion, often associted with tissue damage. -Detects of function of neutrophils and monocytes may affect their chemotaxis, phagocytesis oe killing. ...

Chapter 7 in Haematology (Genetic disorder of haemoglobin) summary   -Genetic disorders of haemoglobin fall into two main groups: 1-The thalassaemias in which synthesis of the alpha or beta globin chain is reduced. 2-Structural disorders in which an abnormal haemoglobin is produced. -The alpha or beta thalassaemias occur clinically as minor forms with microcytic hypochromic red cells and a raised red cell count with or without anaemia.total absece of function of all four alpha globin genes causes hydrops fetalis. -Total absencce of function of both beta globin genes causes beta thalassaemia major , a transfusion –dependent anaemia associated with iron overload. Thalassaemia intermedia is a clinical term for a group of disorder showing mild to moderate anaemia and is usually caused by variants of beta thalassaemia. -The most frequent structural defect of haemoglobin is the sickle mutation in the beta globin chain causing, in the homozygous form, a sever haem...

Chapter 6 in Haematology (Haemolytic anaemias)summary   -Haemolytic anaemia is caused by shorting of the red cell life.The red cells may break down in the reticuloendothelial system (extravascular)or in the circulation (intravascular). -Haemolytic anaemia may be caused by inhrited red cell defects, which are usually intrinsic to the red cell ,or to acquired caused, which are usually caused bu an abnormality of the red cell environment . -Features of extravascular haemolysis include jaundice,gallstones and splenomegaly with raised reticulocytes,unconjugated bilirubin band absent haptoglobins.In intravascular haemolysis (e.g.casued by ABO mismatched blood transfusion),there is haemoglobinaemia ,methaemalbuminaemia ,haemoglobinuria ,and haemosiderinuria . -Genetic defect include those of the red cell membrane (e.g.hereditary spherocytosis),enzyme defiiciencies(e.g.glucose-6-phosphate dehyrogenase or pyruvate kinase deficiency)or haemoglobin defevt (e.g.sickle cell a...

Chapter 5 in Haemtology (Macrocytic Anaemia) summary   -Macrocytic anaemia show an increased size of circulating red cells (MCV>98 fl).Causes include vitamin B12 (B12,cobalamin) or folate deficiency,alcohol,liver disease, hypothyroidism,myelodysplasia, paraproteinneamia, and the neonatal period. - B12 or folate deficiency cause megaloblastic anaemia, in which the bone marrow erythroblast   have a typical abnormal appearance. -B12 deficiency is usually caused by B12 malabsorption brought about by pericious anaemia in which there is autoimmune gastric, resulting in severe deficiency of intrinsic factor, a glycoprotien made in stomach which faciliates B12 absorption by the ileum. -Other gastrointestinal diseases as well as a vegan diet may cause B 12 deficiency . -folate deficiency may be caused by a poor diet ,malabsorption (e.g.gluten-induced enteropathy)or excess cell turnover(e.g.pregnancy,haemolytic anaemias, malignancy) -Treatment of B 12 defici...

Chapter 4 in Heamtology (Iron overload) summary -Iron overload is caused by excessive absorption of iron from food (genetic haemochromatosis ) or by repeated blood transfusions in patients with refractory anaemias. Each unit of blood contains 200-250 mg of iron. -Excess iron aborbed from the gastrointestinal tract accumulates in the parenchymal cells of the liver, endocrine organs and, in sever cases, the heart. -Transfusional iron overload causes damage to these organs and also iron accumulation in macrophages of the reticuloendothelial system.   -Genetic haemochromatosis is usually caused by homozygous mutation (845G to A) of the gene causing a low serum hepcidin level. Rare forms exist caused by mutations of other genes coding for protiens ( hemojuvelin,hepcidin,transferrin receptor 2 ferroportin).Repeated venesections are used to reduce the body iron burden. -Transfsional iron overload most frequently occurs in thalassaemia major but also in other transfusio...

Chapter 3 in hematology ( Hypochromic anemia) summary -           -Iron is present in the body in haemoglobin,myoglobin, haemosiderin and ferritin , and in iron-containing enzymes, transferrin is the main transport protien in blood and hepcidin the main regular of iron absorption and iron relese from macrophages. - Iron Metabolism is regulated according to iron status by intracellular iron regulatory protiens and by control of hepcidin synthesis. -Iron Deficiency is the most common cause of anaemia throughout the world. The surm ferritin, serum iron and saturation of the iron binding capacity are reduced. -In western countries , it is usually caused by haemorrhage from the gastrointestinal or the female genital tract.dietary in take is important particulary i underdeveloped countries. -The red cells are hypochromic and microcytic. It is treated by oral or parenteral iron and by treating, as far as possible, the underlying ...