BIOS222 Pathology and Clinical Science 2
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1 BIOS222 Pathology and Clinical Science 2 Session 4 Lymphatic and Haematological Disorders 2 Bioscience Department
2 Session Learning Outcomes At the end of the session, you should be able to o Classify various types of anaemia in terms of their aetiology and morphology. o Identify the causes, pathophysiology and clinical manifestations of various types of anaemia. o Suggest appropriate investigations and management for the conditions. o Define and describe the haemoglobinopathies in terms of their cause, pathophysiology, role of hereditary trait, treatment and management. Endeavour College of Natural Health 2
3 o The Anaemias: Session Plan Classification of anaemia Iron deficiency anaemia Megaloblastic anaemia Anaemia of chronic disease Haemolytic anaemia Haemoglobinopathies Sickle cell anaemia Thalassemia Endeavour College of Natural Health 3
4 Anaemia Definition: A state in which there is decrease in the level of haemoglobin in the blood below the reference level for the age and sex of the individual. o Normal reference range: (varies with age, gender and ethnic origin of a person) Adult male g/l Adult female g/l Red cell characteristics seen in different types of anemia: (A) microcytic and hypochromic red cells, characteristic of iron deficiency anemia; (B) macrocytic and misshaped red blood cells, characteristic of megaloblastic anemia; (C) abnormally shaped red blood cells seen in sickle cell disease; (D) normocytic and normochromic red blood cells, Images from: Grossman, S, Porth, CM 2013, Porth s pathophysiology, Concepts of Altered Health States, 9th edn, Lippincott Williams & Wilkins Endeavour College of Natural Health 4
5 Classification of Anaemia o Aetiological classification of anaemia: Inadequate nutrients to synthesize RBC Iron deficiency anaemia, Megaloblastic anaemia Excessive loss of RBC Haemolytic anaemia: destruction of RBCs Genetic defect in Haemoglobin synthesis Thalassemia, Sickle cell anaemia Endeavour College of Natural Health 5
6 Classification of Anaemia o Morphological classification of Anaemia Based on size of RBC Macrocytic Normocytic Microcytic Based on Content of Haemoglobin in the RBC Hypochromic Normochromic Endeavour College of Natural Health 6
7 Classification of Anaemia Endeavour College of Natural Health 7
8 General Signs and Symptoms, Anaemia o Symptoms: Fatigue Headache Tinnitus Fainting Breathlessness Angina Palpitation Intermittent claudication o Signs Pallor Tachycardia Systolic flow murmur Cardiac failure Papilloedema Endeavour College of Natural Health 8
9 o Aetiology: Iron deficiency anaemia Blood loss Malabsorption or dietary deficiency of Iron Increased physiological demands o Pathophysiology: Lack of Iron Decreased synthesis of Haemoglobin Decreased RBC size with decreased heamoglobin concentration Microcytic hypochromic anaemia Impaired oxygen transport Endeavour College of Natural Health 9
10 Iron deficiency anaemia Iron digestion, absorption, enterocyte use, transport and distribution Gropper SS and Smith JL, 2013, Advanced Nutrition and Human Metabolism, 6th edn, Wadsworth Cengage Learning, Canada Walker, BR, Colledge, NR, Ralston, SH, & Penman, ID (eds) 2014, Davidson s principles and practice of medicine, 22nd edn, Churchill Livingstone Elsevier, Edinburgh. Endeavour College of Natural Health 10
11 Iron deficiency anaemia o Clinical features: Common symptoms of Anaemia Pallor, Palpitation, Headache, lack of concentration, Shortness of breath Koilonychia Sore ulcers at the corner of the mouth (Glossitis and angular stomatitis) Severe cases may present with murmurs Koilonychia Angular Stomatitis DermNetNz, 2012, New Zealand Dermatological Society Incorporated. Published online at: Endeavour College of Natural Health 11
12 o Diagnosis: Iron deficiency anaemia FBC: Haemoglobin, MCV, MCHC, haematocrit Iron studies: Plasma Iron, Ferritin, Transferrin levels, Total Iron binding capacity Peripheral smear of blood Investigation of the cause Normal peripheral blood smear Iron deficiency anemia peripheral blood smear Endeavour College of Natural Health 12
13 Iron deficiency anaemia o Management: Control chronic blood loss Increase dietary intake of iron Administering supplemental iron Iron transfusion in severe cases Endeavour College of Natural Health 13
14 Iron deficiency anaemia: Low level of haemoglobin in blood due to lack of iron Blood loss, Malabsorption or dietary deficiency of Iron, Increased physiological demands Lack of Iron Decreased synthesis of Haemoglobin Decreased RBC size with decreased heamoglobin concentration Microcytic hypochromic RBCs Impaired oxygen transport to body tissues Epithelial atrophy Pallor Palpitation Headache lack of concentration Shortness of breath Systolic murmurs Waxy pallor, brittle hair and nails Koilonychias Smooth tongue Glossitis and angular stomatitis Dysphagia and decreased acid secretion Diagnosis: FBC Iron studies Peripheral smear of blood Investigation of the cause Management: Control chronic blood loss Increase dietary intake of iron Administering supplemental iron Iron transfusion in severe cases Endeavour College of Natural Health 14
15 Megaloblastic Anaemia o Aetiology: Vitamin B12 deficiency: Dietary deficiency Gastric factors Pernicious anaemia Small bowel factors Folic acid deficiency: Dietary deficiency Malabsorption Increased demand Drugs Absorption of vitamin B12 Gropper SS and Smith JL, 2013, Advanced Nutrition and Human Metabolism, 6th edn, Wadsworth Cengage Learning, Canada Endeavour College of Natural Health 15
16 Megaloblastic Anaemia o Pathophysiology: Lack of B12 and Folate Poor methionine metabolism High plasma levels of homocysteine and impaired DNA synthesis Cell with arrested nuclear maturation but normal cytoplasmic development (megaloblast) All proliferating cells (bone marrow cells, buccal mucosa, tongue, small intestine, cervix, vagina and uterus) exhibit megaloblastosis. Lack of B12 Focal demyelination affecting the spinal cord, peripheral nerves, optic nerves and cerebrum Neurological symptoms Endeavour College of Natural Health 16
17 Megaloblastic Anaemia Bendich, A and Deckelbaum, RJ, (Eds.), 2010, Preventive Nutrition The Comprehensive Guide for Health Professionals, 4th edn, Humana Press Endeavour College of Natural Health 17
18 Megaloblastic Anaemia o Clinical features: Symptoms: Malaise Breathlessness Paraesthesiae Sore mouth Weight loss Altered skin pigmentation Impotence Poor memory Depression Personality change Hallucinations Visual disturbance Endeavour College of Natural Health 18
19 Megaloblastic Anaemia Signs Smooth tongue Angular cheilosis Vitiligo Skin pigmentation Heart failure Pyrexia Neurological findings in B12 deficiency Glove and stocking paraesthesiae Loss of ankle reflexes diminished vibration sensation and proprioception upper motor neuron signs Dementia Optic atrophy Autonomic neuropathy Endeavour College of Natural Health endeavour.edu.au 19
20 Megaloblastic Anaemia o Diagnosis: FBC: Haemoglobin, MCV, Blood cell counts Serum Ferritin Plasma lactate dehydrogenase (LDH) Peripheral smear of blood Bone marrow Investigation of the cause Endeavour College of Natural Health 20
21 o Management: Megaloblastic Anaemia Management of Vit. B12 deficiency Management of Folic acid deficiency Normal peripheral blood smear Megaloblastic anaemia peripheral blood smear Endeavour College of Natural Health 21
22 Dietary deficiency Gastric factors Pernicious anaemia Small bowel factors Megaloblastic anaemia: Low level of haemoglobin in blood due to lack of vitamin B12 or Folic acid Vitamin B12 deficiency Folic acid deficiency Dietary deficiency Malabsorption Increased demand Drugs Focal demyelination affecting the spinal cord, peripheral optic nerves and cerebrum Paraesthesiae Loss of ankle reflexes Diminished vibration sensation and proprioception Upper motor neuron signs Dementia Optic atrophy Autonomic neuropathy Poor methionine metabolism High plasma levels of homocysteine and impaired DNA synthesis All proliferating Cells with arrested nuclear maturation but normal cytoplasmic development (megaloblastosis) Megaloblastosis in cells of bone marrow Buccal mucosa, tongue, small intestine, genital tract Malaise, Breathlessness, weight loss, Smooth tongue, pyrexia, Angular cheilosis, Sore mouth, altered skin pigmentation, Impotence Diagnosis: FBC Serum Ferritin Plasma lactate dehydrogenase (LDH) Peripheral smear of blood Bone marrow Investigation of the cause Management: Management of Vit. B12 deficiency Management of Folic acid deficiency Endeavour College of Natural Health 22
23 Anaemia of chronic disease o Aetiology: Chronic infection Chronic inflammation Neoplasia o Pathophysiology: Pro-inflammatory cytokines in chronic disease Induce hepcidin production by liver cells Hepcidin binds to ferroportin and internalise ferroportin into iron storing cells reduced release of iron Low circulatory Iron Reduced Erythropoiesis Normocytic normochromic anaemia Endeavour College of Natural Health 23
24 Anaemia of chronic disease Walker, BR, Colledge, NR, Ralston, SH, & Penman, ID (eds) 2014, Davidson s principles and practice of medicine, 22nd edn, Churchill Livingstone Elsevier, Edinburgh. Endeavour College of Natural Health 24
25 Anaemia of chronic disease o Diagnosis: FBC: Haemoglobin, MCV Iron studies: Serum Iron, Ferritin, Transferrin levels, Total Iron binding capacity Serum soluble transferrin receptor Bone marrow o Management: Measures to reduce the severity of the underlying disorder Endeavour College of Natural Health 25
26 Anaemia of chronic disease o Differential diagnosis Iron deficiency anaemia Walker, BR, Colledge, NR, Ralston, SH, & Penman, ID (eds) 2014, Davidson s principles and practice of medicine, 22nd edn, Churchill Livingstone Elsevier, Edinburgh. Endeavour College of Natural Health 26
27 Haemolytic anaemia o Definition: Anaemia resulting from increased rate of RBC destruction o Types: Extravascular haemolysis: Rapid red cell destruction in the reticuloendothelial cells in the liver or spleen. No free haemoglobin in the plasma. Intravascular haemolysis: Red cell lysis within the blood stream Free haemoglobin is released into the plasma Endeavour College of Natural Health 27
28 o Aetiology: Haemolytic anaemia Inherited causes of haemolysis Red cell membrane defect: hereditory spherocytosis/elliptocytosis Haemoglobin abnormalities: Thalassemia, sickle cell disease Red cell enzyme deficiencies: G6PD deficiency, Pyruvate kinase deficiency, pyrimidine 5 nucleotidase deficiency Endeavour College of Natural Health 28
29 o Aetiology: Haemolytic anaemia Acquired causes of haemolysis Immune: autoimmune diseases, haemolytic diseases of newborn, transfusion reactions, drug induced Non immune acquired membrane defects, mechanical causes, secondary to systemic diseases related to liver and kidneys, Infections, Drugs and chemicals, Burns Endeavour College of Natural Health 29
30 o Clinical features: Haemolytic anaemia Severe pallor, shortness of breath and heart failure Episodic jaundice in some patients Young children may show failure to thrive Gall bladder stones due to excessive bilirubin formation in chronic cases Increased pulmonary hypertension due to hypoxic conditions and right ventricular failure Endeavour College of Natural Health 30
31 Haemolytic anaemia o Diagnosis: Full blood count Peripheral blood smear Red blood cell enzymes Serum bilirubin, lactate dehydrogenase Urine and stool examination Bone marrow Coomb test for antibodies against red cells o Management: Treatment of underlying cause Corticosteroids Blood transfusion Endeavour College of Natural Health 31
32 Haemoglobinopathies o Definition: The diseases caused by mutations of the genes encoding the globin chains of the haemoglobin molecule. o Types: Qualitative abnormalities Alteration in the amino acids structure/sequence Example: Sickle cell anaemia Quantitative abnormalities reduced rate of production of one or other of the globin chains Example: Thalassemias Endeavour College of Natural Health 32
33 Sickle cell Anaemia o Definition: an inherited disorder in which an abnormal haemoglobin (HbS) leads to chronic haemolytic anaemia, pain, and organ failure. o Aetiology: Inherited as an autosomal recessive trait Substitution of one glutamic acid to valine in the amino acid chain of Beta Haemoglobin o Pathophysiology: Abnormal haemoglobin Sickle shaped RBC Early destruction of RBC Endeavour College of Natural Health 33
34 Sickle cell Anaemia Mechanism of sickling and its consequences in sickle cell anaemia Gropper SS and Smith JL, 2013, Advanced Nutrition and Human Metabolism, 6th edn, Wadsworth Cengage Learning, Canada Endeavour College of Natural Health 34
35 Sickle cell Anaemia o Clinical features: Hypoxia Acidosis Dehydration Infection Acute syndromes: Vaso-occlusive crisis Sickle chest syndrome Sequestration crisis Aplastic crisis Chronic organ damage Endeavour College of Natural Health 35
36 Sickle cell Anaemia Walker, BR, Colledge, NR, Ralston, SH, & Penman, ID (eds) 2014, Davidson s principles and practice of medicine, 22nd edn, Churchill Livingstone Elsevier, Edinburgh. Endeavour College of Natural Health 36
37 Sickle cell Anaemia o Diagnosis: FBC: Hb Blood film examination HbS screening: Exposing red cells to a reducing agent such as sodium dithionite Haemoglobin electrophoresis o Management: Prophylaxis, vaccination Aggressive rehydration, analgesics, O 2, antibiotics, transfusion Allogeneic stem cell transplants Hereditary trait counselling Endeavour College of Natural Health 37
38 Thalassaemia o Definition: an inherited impairment of haemoglobin production, in which there is partial or complete failure to synthesise either the α- or β-globin chains of HbA. o Types: Beta thalassaemia Thalassaemia minor Thalassaemia major Alpha thalassaemia Endeavour College of Natural Health 38
39 o Aetiology: Thalassaemia Beta thalassaemia: Multiple point mutations in the β - globin gene causing a defect in β-chain synthesis Alpha thalassaemia: Deletion of alpha gene alleles on chromosome 16 o Pathophysiology: Genetic mutation reduced rate of production of one or other of the globin chains alpha to non-alpha chains ratio altered the excess chains precipitate within RBC precursors formation of abnormal haemoglobin with less affinity for oxygen RBC membrane damage and haemolysis Microcytic Hypochromic anaemia Endeavour College of Natural Health 39
40 o Clinical features: Beta Thalassaemia Severe, blood transfusion dependent anemia Anaemia Bone marrow hyperplasia early in life. Impaired bone growth and Bone deformities Splenomegaly, Hepatomegaly o Complications: Iron overload leading to Cardiac, hepatic, and endocrine diseases and organ damage Endeavour College of Natural Health 40
41 o Management: Beta Thalassaemia Regular blood transfusions Iron chelation therapy Stem cell transplantation Endeavour College of Natural Health 41
42 Alpha Thalassaemia o Clinical features: related to the number of gene deletions One gene deletion: no clinical effect. Two genes deletion: mild hypochromic anaemia. Three gene deletion: Haemoglobin H disease. Four gene deletion: stillborn baby (hydrops fetalis). o Management: Folic acid supplementation Transfusion if required Avoidance of iron therapy Endeavour College of Natural Health 42
43 Reading and Resources o o o o o o o Crowley LV, 2012, An Introduction to Human Diseases Pathology and Pathophysiology Correlations, 9th edn, Jones and Bartlett Learning Grossman SC & Porth CM 2014, Porth s Pathophysiology- Concepts of Altered Health States, 9th edn. Wolters Kluwer Health - Lippincott, Williams & Wilkins Hinson, J, Raven, P & Chew, S 2010, The endocrine system: basic science and clinical conditions, 2nd edn, Churchill Livingstone Elsevier, Edinburgh Jamison, JR 2006, Differential diagnosis for primary care: a handbook for health care practitioners, 2nd edn, Churchill Livingstone Elsevier, Edinburgh. Jarvis, C, 2012 Physical Examination & Health Assessment, 6th ed., Elsevier Saunders, Philadelphia. Kumar, P & Clark, M 2012, Kumar and Clark s clinical medicine, 8th edn, Saunders Elsevier, Edinburgh. Kumar, V, Abbas, AK & Aster, JC 2015, Robbins & Cotran pathologic basis of disease, 9th edn, Elsevier Saunders, Philadelphia. Endeavour College of Natural Health 43
44 o o o o o o Reading and Resources Lee, G & Bishop, P 2009, Microbiology and infection control for health professionals, 4th edn, Pearson Education, Frenchs Forest, NSW. McCance, KL, Heuther, SE, & Brashers, VL 2014, Pathophysiology: the biologic basis for disease in adults and children, 7th edn, Elsevier. Michael-Titus, A, Revest, P & Shortland, P 2010, The nervous system: basic science and clinical conditions, 2nd edn, Churchill Livingstone Elsevier, Edinburgh Mosby s dictionary of medicine, nursing and health professions 2013, 9th edn, Elsevier, St. Louis, MO. Tortora, GJ & Derrickson, B 2014, Principles of anatomy and physiology, 14th edn, John Wiley & Sons, Hoboken, NJ. VanMeter, KC & Hubert, RJ 2014, Gould's pathophysiology for the health professions, 5th edn, Elsevier, St Louis, MO. o Walker, BR, Colledge, NR, Ralston, SH, & Penman, ID (eds) 2014, Davidson s principles and practice of medicine, 22nd edn, Churchill Livingstone Elsevier, Edinburgh. Endeavour College of Natural Health 44
45 COMMONWEALTH OF AUSTRALIA Copyright Regulations 1969 WARNING This material has been reproduced and communicated to you by or on behalf of the Endeavour College of Natural Health pursuant to Part VB of the Copyright Act 1968 (the Act). The material in this communication may be subject to copyright under the Act. Any further reproduction or communication of this material by you may be the subject of copyright protection under the Act. Do not remove this notice. Endeavour College of Natural Health 45
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