Day: April 29, 2024

Microcytic Anaemia A problem in haemoglobin results in the improper folding in RBC leading to a reduced cell mass. – Due to the structure of haemoglobin, it is caused by deficits in haem group or Hb chains themselves.   Iron Deficiency Anaemia (IDA) This is a microcytic anaemia which occurs due to decreased levels of iron, most common worldwide.   Causes: – Blood loss –> GI bleeding or menstruation (seen in 14% of women) – Poor diet –> seen in babies or children – Malabsorption –> coeliac disease, due to inflammation of the small bowel   Symptoms: – General signs

Normocytic Anaemia This refers to anaemia with normal-sized RBCs (MCV = 80-100). It is mainly due to 2 types of disease: – Increased peripheral destruction –> haemolytic anaemias – Underproduction by the bone marrow –> aplastic anaemia, chronic kidney disease – To distinguish between peripheral destruction and underproduction by the bone marrow, you look at the reticulocyte count  Reticulocyte Count   Intravascular Haemolysis These conditions involve destruction of RBCs within blood vessels and lead to following signs: – Haemoglobinaemia –> raised free plasma Hb in serum – Haemoglobinuria –> this causes tea-coloured urine – Decreased Plasma haptoglobin –> This mops

Myeloproliferative Disorders This is a neoproliferation of mature cells of the myeloid lineage – it is a disease of late adulthood – Cells of all myeloid lineages are increased but the disease is classified based on main cell type produced. – They are associated with mutations in JAK2 kinase – Main complications are risk of ­ ↑ uric acid (gout) due to high cell turnover, bone marrow fibrosis and progression to an acute leukaemia.    Polycythaemia Vera (RBC) This is a proliferation of RBCs, which are unusual as they do not require erythropoietin to survive – Almost all of these

Plasma Cell Disorders Abnormal plasma cell proliferation gives excessive secretion of immunoglobin giving organ dysfunction. – The urine of these patients contains Bence Jones proteins (free Ig chains) which are filtered by the kidney.   Multiple Myeloma This is due to proliferation of plasma cells in the bone marrow, usually seen around age of 70. – Plasma cells crowd out hematopoiesis, activate osteoclasts and produce excessive levels of antibodies.   Symptoms – These primarily are caused by increased osteoclast activity and Ig production i) Osteoclast activity: – Bone pain –> osteoclasts cause bone resorption with punched out lesions – Hypercalcemia

Lymphomas This is a neoplastic proliferation of lymphocytes which accumulate in lymph nodes or tissue forming a mass – They are divided into Hodgkin’s lymphoma (characterized by Reed-Sternberg Cells) and Non-Hodgkin’s   Hodgkin Lymphoma (HL) This is a malignant proliferation of Reed-Sternberg (RS) cells. These are large B cells with prominent nucleoli in their multilobed nuclei (owl eyed nuclei) – The RS cells are CD15 and CD30, and secrete cytokines giving B cell symptoms – They attract inflammatory cells which make up the tumour bulk – It usually occurs in a bimodal distribution – seen in 20s and in 60-70-year-old

Acute Leukaemia This is the neoplastic proliferation of (WBC precursors “blasts”), defined as >20% blasts in bone marrow – Increased blasts disrupt normal hematopoiesis, resulting in a quick-onset presentation with anaemia (fatigue), thrombocytopenia (bleeding) and neutropenia (infection).   Acute Lymphoblastic Leukaemia (ALL) This is a neoplastic proliferation of immature lymphoblasts in the bone marrow, which leads to bone marrow failure and tissue infiltration. It is the most common malignancy of childhood (rarer in adults) – The cancer cells have a marker, which is the enzyme TdT and are divided into B or T cell lymphoblasts – B cell lymphoblasts display

Platelet Disorders These can arise due to decreased bone marrow production, excess destruction or poor functioning – These abnormalities are divided into quantitative (low platelet count due to bad supply or removal) and qualitative disorders (where there is a problem with the structure or function of the platelet) – Clinical features usually involve mucosal and skin bleeding. – Skin bleeding –> leads to petechiae + Purpura (3mm) + Easy bruising. – Mucosal bleeding –> leads to epistaxis (most common symptom) + GI bleeding + hematuria Qualitative Platelet Disorders   Immune Thrombocytopenic Purpura (ITP) This is an autoimmune production of antibodies

Clinical Chemistry Sodium     Hyponatraemia This is a low concentration of plasma Na+. As the concentration depends on both sodium levels and water volume, hyponatreamia can either be due to a lack of sodium ions or too much water.   Causes: The main way to distinguish the causes is first assessing if the patient is dehydrated or full of water. – If dehydrated, this suggests the primary problem is losing Na+ ions, and water indirectly follows as a result. –> Kidney etiology – Addison’s disease or renal failure –> Outside kidneys – Burns, diarrhea, small bowel obstruction   –

Clinical Chemistry Sodium     Hyponatraemia This is a low concentration of plasma Na+. As the concentration depends on both sodium levels and water volume, hyponatreamia can either be due to a lack of sodium ions or too much water.   Causes: The main way to distinguish the causes is first assessing if the patient is dehydrated or full of water. – If dehydrated, this suggests the primary problem is losing Na+ ions, and water indirectly follows as a result. –> Kidney etiology – Addison’s disease or renal failure –> Outside kidneys – Burns, diarrhea, small bowel obstruction   –

Clinical Chemistry Sodium     Hyponatraemia This is a low concentration of plasma Na+. As the concentration depends on both sodium levels and water volume, hyponatreamia can either be due to a lack of sodium ions or too much water.   Causes: The main way to distinguish the causes is first assessing if the patient is dehydrated or full of water. – If dehydrated, this suggests the primary problem is losing Na+ ions, and water indirectly follows as a result. –> Kidney etiology – Addison’s disease or renal failure –> Outside kidneys – Burns, diarrhea, small bowel obstruction   –

Coagulation Disorders These disorders are caused by a problem relating to one or more of the factors in this coagulation cascade. – Typically, they lead to delayed bleeding from joints and muscle and also after surgery.   Haemophilia A This is a genetic deficiency of Factor VIII – It is inherited in an X-linked recessive pattern (mostly affects males) but also spontaneous mutation   Symptoms: – Deep tissue, joint (haemarthroses) and prolonged post-surgical/trauma bleeding – This can lead to haemophiliac arthropathy (resembles osteoarthritis but due to recurrent hemarthroses)   Tests: – Raised APTT and low Factor VIII assay – Normal

Coagulation Disorders These disorders are caused by a problem relating to one or more of the factors in this coagulation cascade. – Typically, they lead to delayed bleeding from joints and muscle and also after surgery.   Haemophilia A This is a genetic deficiency of Factor VIII – It is inherited in an X-linked recessive pattern (mostly affects males) but also spontaneous mutation   Symptoms: – Deep tissue, joint (haemarthroses) and prolonged post-surgical/trauma bleeding – This can lead to haemophiliac arthropathy (resembles osteoarthritis but due to recurrent hemarthroses)   Tests: – Raised APTT and low Factor VIII assay – Normal

Anaemia: Overview Anaemia is defined as a low haemoglobin (Hb) concentration, which can be either due to a reduced RBC mass or increased plasma volume (e.g. in pregnancy) – It is <135g/L for men and <115g/L for women – Subdivided by the mean corpuscular volume (MCV) into microcytic (MCV<80um3), normocytic (80-100) and macrocytic (MCV > 100).   Symptoms: – Weakness, fatigue and dyspnea – Pale conjunctiva and skin – Headaches + light headedness – Angina –> especially if there is pre-existing coronary artery disease (+ aortic flow murmur) – Can be signs of a hyperdynamic circulation due to compensation (tachycardia,

Plasma Cell Disorders Abnormal plasma cell proliferation gives excessive secretion of immunoglobin giving organ dysfunction. – The urine of these patients contains Bence Jones proteins (free Ig chains) which are filtered by the kidney.   Multiple Myeloma This is due to proliferation of plasma cells in the bone marrow, usually seen around age of 70. – Plasma cells crowd out hematopoiesis, activate osteoclasts and produce excessive levels of antibodies.   Symptoms – These primarily are caused by increased osteoclast activity and Ig production i) Osteoclast activity: – Bone pain –> osteoclasts cause bone resorption with punched out lesions – Hypercalcemia

This is a group of rare disease causes by various errors of porphyrin biosynthesis, genetic or acquired. – Porphyrin is made in a series of enzyme reactions. – Depending on the faulty part, there is accumulation of either porphyrinogens (unstable precursors of porphyrins) or initial reactants like d-aminovulinic acid. – The initial reactants are neurotoxic, whilst porphyrins induce photosensitivity + free radical formation.   Acute intermittent porphyria This is an autosomal dominant condition due to a defect in porphobilinogen deaminase, which is much more common in females – The results in the toxic accumulation of d-aminolaevulinic acid and porphobilinogen –

Sodium     Hyponatraemia This is a low concentration of plasma Na+. As the concentration depends on both sodium levels and water volume, hyponatreamia can either be due to a lack of sodium ions or too much water.   Causes: The main way to distinguish the causes is first assessing if the patient is dehydrated or full of water. – If dehydrated, this suggests the primary problem is losing Na+ ions, and water indirectly follows as a result. –> Kidney etiology – Addison’s disease or renal failure –> Outside kidneys – Burns, diarrhea, small bowel obstruction   – If not

Abnormal plasma cell proliferation gives excessive secretion of immunoglobin giving organ dysfunction. – The urine of these patients contains Bence Jones proteins (free Ig chains) which are filtered by the kidney.   Multiple Myeloma This is due to proliferation of plasma cells in the bone marrow, usually seen around age of 70. – Plasma cells crowd out hematopoiesis, activate osteoclasts and produce excessive levels of antibodies.   Symptoms – These primarily are caused by increased osteoclast activity and Ig production i) Osteoclast activity: – Bone pain –> osteoclasts cause bone resorption with punched out lesions – Hypercalcemia –> increase bone

This is a neoproliferation of mature cells of the myeloid lineage – it is a disease of late adulthood – Cells of all myeloid lineages are increased but the disease is classified based on main cell type produced. – They are associated with mutations in JAK2 kinase – Main complications are risk of ­ ↑ uric acid (gout) due to high cell turnover, bone marrow fibrosis and progression to an acute leukaemia.    Polycythaemia Vera (RBC) This is a proliferation of RBCs, which are unusual as they do not require erythropoietin to survive – Almost all of these patients have

Lymphomas This is a neoplastic proliferation of lymphocytes which accumulate in lymph nodes or tissue forming a mass – They are divided into Hodgkin’s lymphoma (characterized by Reed-Sternberg Cells) and Non-Hodgkin’s   Hodgkin Lymphoma (HL) This is a malignant proliferation of Reed-Sternberg (RS) cells. These are large B cells with prominent nucleoli in their multilobed nuclei (owl eyed nuclei) – The RS cells are CD15 and CD30, and secrete cytokines giving B cell symptoms – They attract inflammatory cells which make up the tumour bulk – It usually occurs in a bimodal distribution – seen in 20s and in 60-70-year-old

Leukaemias This is a neoplastic proliferation of WBC cell types which do not form a mass, divided into acute and chronic: Leukhaemias will usually be diagnosed in the follow pathway: – FBC –> shows raised WBC count – Blood smear –> shows presence of tumour cells in the blood – Bone marrow biopsy with immunophenotyping is diagnostic –> shows >20% blasts with cell markers – CT staging scan allows for staging and to look for organ involvement NICE Referral Guidelines   Acute Leukaemia This is the neoplastic proliferation of (WBC precursors “blasts”), defined as >20% blasts in bone marrow –

Coagulation Disorders These disorders are caused by a problem relating to one or more of the factors in this coagulation cascade. – Typically, they lead to delayed bleeding from joints and muscle and also after surgery.   Haemophilia A This is a genetic deficiency of Factor VIII – It is inherited in an X-linked recessive pattern (mostly affects males) but also spontaneous mutation   Symptoms: – Deep tissue, joint (haemarthroses) and prolonged post-surgical/trauma bleeding – This can lead to haemophiliac arthropathy (resembles osteoarthritis but due to recurrent hemarthroses)   Tests: – Raised APTT and low Factor VIII assay – Normal

Platelet Disorders These can arise due to decreased bone marrow production, excess destruction or poor functioning – These abnormalities are divided into quantitative (low platelet count due to bad supply or removal) and qualitative disorders (where there is a problem with the structure or function of the platelet) – Clinical features usually involve mucosal and skin bleeding. – Skin bleeding –> leads to petechiae + Purpura (3mm) + Easy bruising. – Mucosal bleeding –> leads to epistaxis (most common symptom) + GI bleeding + hematuria Qualitative Platelet Disorders   Immune Thrombocytopenic Purpura (ITP) This is an autoimmune production of antibodies

Normocytic Anaemia This refers to anaemia with normal-sized RBCs (MCV = 80-100). It is mainly due to 2 types of disease: – Increased peripheral destruction –> haemolytic anaemias – Underproduction by the bone marrow –> aplastic anaemia, chronic kidney disease – To distinguish between peripheral destruction and underproduction by the bone marrow, you look at the reticulocyte count  Reticulocyte Count   Intravascular Haemolysis These conditions involve destruction of RBCs within blood vessels and lead to following signs: – Haemoglobinaemia –> raised free plasma Hb in serum – Haemoglobinuria –> this causes tea-coloured urine – Decreased Plasma haptoglobin –> This mops