Task 1
1. Explain why ‘communication is critical’ with respect to issuing blood products and patient care.
2. Chronic Myeloid Leukaemia (CML) is a tri-phasic disease. In brief, explain the diagnostic parameters associated with each phase and likely treatment options.
3. Explain the role of core binding factor and its association with specific disease subtypes in AML.
4. Describe how ‘patient sample turn around times’ impact on diagnosis, prognosis and management within the NHS.
5. Describe the feedback loop by which thrombopoietin regulates platelet production.
6. Briefly describe the process which gives rise to the red cells extreme degree of deformability?
7. Give 2 examples of common blood biomarkers of liver dysfunction. By what principle are these markers quantified? Why do these biomarkers have limited predictive power?
8. Give an overview of the mechanisms that are triggered upon an increase in plasma osmolarity that lead to increased water retention in the kidney. How do you think that the stimulus will be switched off?
Task 2
1. Describe how anaemia is classified and name key distinctive features or associations for each. Describe how transferrin, folate and vitamin B12 are associated with anaemia. Use diagrams where appropriate.
2. Describe the processes by which platelets contribute to homeostasis.
3. Indicate the current clinical management of haemolytic disease of the fetus and newborn
4. Critically discuss the use of serum bilirubin as a biomarker for liver dysfunction
5. Inborn errors of metabolism arise from the lack or deficiency of a particular enzyme?
Communication is an important step while issuing the blood products as with communication one could the proper information regarding the identification of patients along with making cross-match of the samples. Communicating to patients is necessary as it will benefit the infusion of right blood at right time. By the communication one can ensure that it all the procedure followed for the treatment is accurate for the patient.
Chronic myeloid leukemia (CML) is referred as the one of the common form of leukemia and it is considered as tri-phasic disease i.e. consisting three phases which are chronic phase, acute phase and blastic phase. Chronic phase is often diagnosed by a pathogenic test for detection of t(9;22)(q34;q21), florescence in-situ hybridization, PCR analysis and southern blot is also done. For analyzing acute phase, the increase in blast count is reported in bone marrow and peripheral blood. Detection of the complication is done by cytogenetic analysis and karyotyping. To diagnose the blastic leukemia immuno phenotyping and cytochemistry is necessary. For lymphoblastic leukemia the lymphoblastic transformation responds to the treatment (Thyss et al, 1997).
Core binding factor CBF-AML is referred as collective incorporation of AML with t(8;21) or inv(16). In the clinical drug intervention the treatment of CBF-AML have develop in giving the favorable outcome in patient. The alteration in CBF-AML might help to understand the leukemogenesis and in the present scenario it is known as the target of novel therapeutic approaches.
This term is referred to the patient flow and it describes the theories linked to the flow of patient and healthcare management. It tags many of the tools and techniques related to the progressive development of the products and information regarding targeted population. With NHS the impact on the diagnosis, prognosis and management consist the movement of the patients, department and staff involved in the patient care pathways.
Thrombopoitien is produced in the liver and it is not regulated at transcriptional or translational level. This molecule comes to the circulation and is been elicitby high affinity through receptor on the surfaces of platelets that intervenes and destroys the available throbopoitein. The feedback loop in circulating platelets regulates the ambient cytokine and chemokines in circulation. The metabolism of thrombopoetein is regulated when there is reduction in the platelet production rate that increases the level of platelet and megakaryocytes in bone marrow that produces platelets (Schmaieret al, 2011).
The deformity in the red cells at extreme is referred as sickle cell disorder (SCD) normally characterized by anomalies in hemoglobin in red blood cell called as hemoglobin S (HbS) possessing less oxygen bearing potential. This defect having less oxygen potential causes polymerization of deoxygenated hemoglobin leads to the flexibility in erythrocyte and rheological effects (Igwegbe et al, 2015).
The common blood biomarkers of the liver dysfunction are alanine aminotransferase (ALT) and aspartate aminotransferase (AST)/ALT ratio. ALT is enzyme available in the liver and is been validated as biomarker for liver dysfunction. When there is deformity in the liver the ALT released into blood stream and it is valid in the diagnosis for liver cirrhosis, hepatitis and jaundice. Another valid marker is Aspartate aminotransferase (AST) as it indicates the hepatocellular injury. The ratio of AST/ALT is analyzed for liver dysfunction where the ration of these goes greater than two (Adams, 2011).
The mechanism that is triggered after increase in plasma osmolarity is known as ‘thirst mechanism’. The symptom of this consequence is water intake after thirst, kidney producing concentrated urine by ADH release. Increase in plasma osmolarity causes dry mouth that stimulates the hypothalamic thirst centers. At the end there are some osmoregulators that provide the feedback and inhibit the thirst centers maintaining osmotic changes.
Use separate booklets to answer questions individually. Include diagrams where appropriate
Anemia is defined as a situation characterized by loss of erythrocyte mass and it is classified on the basis of cytometry, erythrokinetic and biochemical basis.on cytometric basis they are classified as normocytic anemia, hemolytic anemia, aplastic anemia.folate and vitamin B12 are associated with the normocytic anemia where there is disappearance of bone marrow precusrssor. While transferrin is an iron binding blood glycoprotein, that represent the anemia that is caused by iron deficiency.
In the homeostasis platelets participate in two ways, first they perform cohesive function that helps to design hemostatic plug. In another approach they trigger the mechanism of coagulation and expose phospholipid surface that acts as a catalytic sites for the consolidation of hemostatic plug and to promote homeostasis plate should be efficient to perform these properties (Wagner and Burger, 2003)
Haemolytic disease for newborn is the main cause of fetus loss and death amongst the newborn. In this disease the RBC of newborn are attacked by antibodies of mother which starts in the womb itself and causes incompatibility in blood with mother. Management of antenatal care in routine that includes the screening of all expected mother having risk is to be screen and preventive treatment is given accordingly to reduce the occurrence of HDN.
Bilirubin is known hemetoidin and referred as breakdown product of heme catabolism and used as biomarker for liver dysfunctioning. Bilirubin is basically hydrophobic in nature and is bound to albumin while circulating. Bilirubin is transported to the hepatocytes by UDP-Glucuronyl transferase and secreted to bile by CMOAT at intestine. In intestine the conjugated bilirubin is digested and convert bilirubin into urobilinogen. The urobilinogen is converted to stercolinin and indicates as potential liver dysfunction and cholestasis (Kao et al, 2012).
Explain the general consequences of in-born errors using at least two examples from the metabolism of simple sugars and/or glycogen to illustrate this, including consideration of the major symptoms of these conditions and how they arise.
There is a disease called as Galactosemia which is caused by defect in enzyme galactose-1-phosphate uridyl transferase and is known to cause liver failure during infancy. It follows the autosomal recessive mode of inheritance and denotes the enzyme responsible for glucose degradation (Isselbacher et al, 1986). The infants who are suffering through this disease possess the symptoms like vometting, diarrhea and jaundice. To diagnose the disease in early setting it is done before birth from the fluid around the fetus called amniocentesisor from placenta.
References
Adams, L. A. (2011). Biomarkers of liver fibrosis. Journal of Gastroenterology and Hepatology. 26(5): pp. 802-809.
Igwegbe, I., Onojobi, G., Fadojutimi-Akinsiku, M. O., Hirsh, A. M., Park. N. J., Yao, M., Driver, V. R. (2015). Case studies evaluating transdermal continuous oxygen for the treatment of chronic sickle cell ulcers. Advances in Skin and Wound Care. 28(5): pp. 206-210.
Isselbacher, K. J., Anderson, E. P., Kurahashi, K., Kalckar, H. M. (1986). Congenital galactosemia, a single enzymatic block in galactose metabolism. Science. 13 (123): pp. 635–636.
Kao, T. W., Chou, C. H., Wang, C. C., Chou, C. C., Hu, J., Chen, W. L. (2012). Associations between serum total bilirubin levels and functional dependence in the elderly. Internal Medicine Journal. 42 (11): pp.1199–207.
Schmaier, A. A., Stalker, T. J., Runge, J. J., Lee, D. (2011). Occlusive thrombi arise in mammals but not birds in response to arterial injury: evolutionary insight into human cardiovascular disease. Blood 118 (13): 3661–3669.
Thyss, A., Suciu, S., Bertrand, Y., Mazingue, F., Robert, A., Vilmer, E., Mechinaud, F., Benoit, Y., Brock, P., Ferster, A., Lutz, P., Boutard, P., Marguerite, G., Plouvier, E., Michel, G., Plantaz, D., Munzer, M., Rialland, X., Chantraine, J. M., Norton, L., Solbu, G., Philippe, N., Otten, J. (1997). Systemic effect of intrathecal methotrexate during the initial phase of treatment of childhood acute lymphoblastic leukemia. The European Organization for Research and Treatment of Cancer Children’s Leukemia Cooperative Group. Journal of Clinical Oncology. 15(5): pp.1824-30.
Wagner, D. D, Burger, P. C. (2003). Platelets in inflammation and thrombosis. Arteriosclerosis Thrombosis and Vascular Biology. 23 (12): 2131–2137.
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