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Describe in words (without using figures/diagrams) normal haemopoiesis in adults. Include in your description which cells are precursors for the mature cells that are normally found in the peripheral blood circulation. (word limit:650 words)(20 MARKS)
Haemopoiesis: Located in bone marrow section of an adults and lymphatic tissue is the production of platelets and blood cells while replacing old cells removed from distribution by which immature precursor cells expand to mature blood cells. This process thesis and how it works is known as monophyletic theory. The cellular blood components are precursor to haematopoietic stem cells (HSC) that forms blood cells and immune cells. Blood cells (BC) are significant in maintenance of immune system in all types of cells which prompt the BC to constantly maintain self renewal. Haemapoiesis stem cells therefore can proliferate, differentiate and even undergo cell death called apoptosis.
Morphology and growth of BC sometimes occurs outside the bone marrow called extramedullary haemopoiesis. This is abnormal condition associated with Myelofibrosis caused by disorder in the bone marrow caused by stem cell replaced by collagenous connective tissues. Sources of HSC's are bone marrow, peripheral blood, Foetal Hematopoietic, and Embryonic Germ Cells. The vascular compartment of bone marrow is used to supplied nutrient artery and open into sinuses. The sinus carries the blood from the bone marrow to the body.
HSCs include long term stem cells which incorporate transplantation of a new marrow cells to lethally cancerous patients and restore its haemopoietic system and short term progenitor which are unable to renew themselves for longer period but immediately regenerate all types of blood cells. Large amount of new blood cells are constantly been produced in the peripheral blood circulation ensuring steady flow known as pluripotential stem cell (PSC). PSC however differentiates into other stem cells known as unipotential stem cells which are precursor to specialised mature blood cell includes; erythropoiesis, monocytes, granulopoiesis, thrombopoiesis and lymphopoiesis.
Erythropoiesis: Used to describe red blood cells (erythrocytes) formation exclusively in the red bone marrow (RBM). The yellow bone marrow initially composed of fats and subsequently changed to RBM from demand of red blood cells. Haemocytoblasts is the precursor of erythrocytes lasting for few days and involved around four mitotic divisions of cells given rise to 8 to 16 more cells.
The kidney initiates RBC production in mature cell by responding to oxygen shortages in the blood. Erythropoietin hormone is then secreted and transferred to red bone marrow to begin production of red blood cell which fills up the blood capillaries for distribution in the body.
Monocytes: White blood cells which mature to much larger cells called macrophages playing major role in immune system, destroying dead cells and cancer cells. Produced in the bone marrow from nucleated precursors of the monoblast and promonocyte which then enter the bloodstream for circulation to the spleen, lymph nodes, liver, bone marrow and lungs. Mature cells in monocytes life span is around 3-8 hours with full antigenic stimulation of T and B lymphocytes.
Thrombopoiesis: Platelets formed in the cytoplasm cell called megakaryocyte inside bone marrow which matured within 10 days from much larger stem cells ( megakaryoblast) . The platelets formation penetrates into the blood vessels to prevent bleeding, while assisting in clots formation and repair damages. Macrophages eventually destroy the platelets in the spleen and liver.
Granulopoiesis are formed in the red bone marrow (RBM) called granulocytes and subdivided into three types of white blood cells (WBC); eosinophils, neutrophils and basophils and are grouped in the same stem cells called myeloblast.
Lymphopoieses are precursor to lymphoblasts and prolymphocytes produced in bone marrow. Immature cells are transferred to the lymphoid tissues and thymus, with further division with similar antigens to T cells, B cells and NK cells. They mediate composite and immune effectors.
Leukemia and Lymphoma are some of the cancer of the blood associated with treatment by HSCs. The process relates to the patient's defective white blood cells causes by cancers destroyed using chemotherapy and replaced with bone marrow transplant matched with donors with similar leukocytes antigens. Cancer of the blood is acute or chronic myeloblastics leukemia, multiple myeloma, non-Hodgkin's lymphoma and Hodgkins diseases.
(Word count is 650)
Name the systems used to classify acute lymphoblastic leukaemia(ALL) and acute myeloid leukaemia (AML). (word limit: 20 words) (2 MARKS)
French-American-British (FAB) classification and the World Health Organization (WHO) classifications are two subtypes used in classification of AML and ALL.
(Word count is 20)
Define leucocytosis and thrombocytopenia. (word limit: 75 words)(5 MARKS)
Leucocytes is a conditions of an abnormal increase of white cells in the blood due to infections. Total white blood cells are approximately 4400 to 11,000 cells/microL. Excess to the value of 50,000/microL, attributed to leukemia is called leukemoid reaction.
Thrombocytopenia is a condition where there is abnormal decrease in platelets counts, rendering inability for clot formation resulting in excessive bleeding. Causes can be due to low platelets in bone marrow, intravascular and extravascular. (Word count is 74)
Define leukaemia and state the four main divisions of the disease. (word limit: 70 words) (10 MARKS)
Leukaemia is a malignant (cancer) of the bone marrow characterized by uninhibited proliferation of abnormal white blood cells. Symptoms include enlargement of liver, lymph nodes and spleen, anaemia, blood clotting retardation.
Four major types of leukaemia are; Acute lymphoblastic leukaemia (ALL) and Chronic lymphocytic leukaemia (CLL) classified as Lymphocytic or lymphoblastic, Acute myeloid leukaemia (AML) and Chronic myeloid leukaemia (CML) classified as Myelogenous leukemia (Word count is 64)
State the typical manifestation of someone presenting with acute leukaemia including the blood film morphology. (word limit: 200 words) (5 MARKS)
Most common symptons includes abnormal bruising and bleeding (thrombocytopaenia), anemia, bleeding gums or irregularity in menstrual period and infections. Anaemia and hypermetabolic state are attributed to fatigue, malaise, weight loss, chest pain and tachycardia. Granulocytopenia can progressively lead to potential life threatening bacterial infections. Developing infection frequently in eyes, nose and mouth known as neutropaenia, trace of blood in urine, fine rash dark red spots called purpura.
Sign of fever, abnormal heamostasis are mostly common. Patients may sometimes shows lesion in soft tissues, spina dura and cranial representing tumour of leukaemia cells called granulocytic sarcoma or chroma. Periosteal infiltration and bone marrow may initiate joint pain (Arthralgia) in children with ALL. Meningitis causing vomiting, seizure, papilledema and headache is rare.
Blood film morphology diagnosis of AML shows presence of more than 20% myeloblasts in blood cell. Cells appear to be smudge with decrease in thrombocytes. Elevated count of leucocytes 135.3 x 109 /L and thrombocytopenia of 26 x 109 /L indicates signs of acute leukaemia.
In AML, Auer rods appear smaller in size, absent of granules, lower RBC counts and appear smaller in morphology while ALL contains no granules. (Word count is 189)
State the typical manifestation of someone with chronic leukaemia including the blood film morphology. (word limit: 200 words) (5 MARKS)
Chronic leukaemia from mature cells is a slow progressive symptom that goes unnoticed for months. Disease is normally notice during normal routine blood test. Immediate treatment is not imminent and may involve chemotherapy treatment in tablet form. Chronic leukaemia types include; chronic lymphocytic leukaemia (CLL), lymphocytes cancer and
Chronic myeloid leukaemia (CML), myeloid cancer. Chronic lymphocytic leukaemia (CLL) is the most common type characterised by an increased number of lymphocytes (WBC). The lymphocytes are unable to perform normal process of responding to infections by producing antibodies needed to destroy bacteria.
Symptoms may be tiredness (anaemia) due to lack of RBC, continuous infections due to WBC's shortages in fighting infections, abnormal lymphocytes in lymph glands causing swelling in neck and arm pits or groin, swelling in spleen, Low platelets in blood leading to bruising or bleeding without injury, weight loss, fevers and night sweat.
Test in blood film morphology indicates nuclei appearance is rounded and condensed chromatin. Increased level of beta-2-macroglobulin protein in the blood. Appearance and large amount of lymphocytosis in the blood of more than 10,000 lymphocytes/mm³ shows presence of the disease. Patient with CLL often have low red blood cells and blood platelets in the body.
(Word count is 200)
Explain the following techniques and give one example for each, of application in the diagnosis or monitoring of leukaemia: (word limit: 230) (15 marks).
Staining methods use to study, identify and localization of various chemical compounds within living cells and activities of acute leukaemia. Method of diagnosing leukaemia is Myeloperoxidase (MPO) staining which can be completed within minutes. Main function is to differentiate AML and ALL. Lysosomal enzyme stored azurophilic granules of neutrophils and monocytes. Used in basophils and eosinophils demonstration. Heme pigmentation reacts to its green colour secretion found in neutrophils.
Use to analyze heterogeneous populations of cells based on the antigens phenotype according to their resemblance of interest. Example is leukocytes from peripheral blood extract from lymph nodes, leukaemia and lymphoma specific to differentiate cancer cells to normal immune system. Used on a daily basis from normal biopsies to bone marrow biopsies and also to analyze and arrange T-lymphocytes into subsets based on CD antigens in flow cytometry techniques. Cells samples are analyzed in a multi-well plate with aid of fluorescence or scatter laser light to sort out population by immunophenotypic markers type.
The branch of genetics specialized in the studies of relationships between the structure of cell division and chromosomes relating to variation in phenotype and genotype. Tests are carried out in blood and bone marrow from leukaemia patients to analyse abnormalities in chromosomal link with certain disease.
Fluorescent in situ hybridization (FISH) is one of the methods use in routine analysis of cytogenetic band, molecular cytogenetic and G-Banded chromosomes in leukemia against normal chromosome.
(Word count is 228)
What is the Philadelphia chromosome? Give an example of where this is commonly found. (word limit: 120 words) (5 MARKS)
Philadelphia chromosome (PH) or Philadelphia translocation is a chromosomal deformity that causes chronic myelogenous leukemia (CML). It is an abnormally chromosome 22 involved in an exchange with chromosome 9 which occur at the site of single bone marrow cell and can also be located in form of acute lymphoblastic leukemia (ALL).
The clonal process expands to the leukaemia and was the first major mutant cell found in malignancy which led to the CML cells combination of BCR-ABL gene protein. These genes belong to chromosome 22 and 9 respectively. Both PH chromosome fused together causing uncontrolled malignant in the cell is a strong indication of pathogenic disease. Mesylate (Gleevec) drug was introduced to aid in this particular cancer treatment. (Word count is 119)
State the difference between stem cell and bone marrow transplants. (word limit: 100 words) (4 MARKS)
Stem cell transplantation is a method where the stem cells are obtained from the peripheral blood using aphaeresis method. Aphaeresis assists in stem cells filtrations and avoids unwanted blood. This practise on out patients is less invasive and requires recovery very quickly at home.
Stem cell harvested from the bone marrow using fine needle inserted into the hip joint however required critical method from in patient to be hospitalized and put under general anaesthesia for continue monitoring.
Stem cells extracted from the bone marrow contain richer stems compare with stem collected from the peripheral blood. (Word count is 97)
State the difference between autologous and allogenic transplants. (word limit: 50 words) (4 MARKS)
Difference between an autologous transplant is when patient's own blood forming cell are collected for use in transplantation later, while an allogenic transplant relies on cells collected from volunteer's bone marrow. The donor's tissue type must be compatible to the recipient to avoid miss match. (Word count is 45)