2022 PSL301H Blood and Immune System Lecture 1 (PDF)

PSL301H—Blood and Immune System Lecture 1: Intro and Red blood cells Learning objectives List the functions of blood Outline the constituents of blood and their functions Understand the process of hematopoiesis Describe the removal of old red blood cells Describe the symptoms of anemia and its possi...

PSL301H—Blood and Immune System Lecture 1: Intro and Red blood cells Learning objectives List the functions of blood Outline the constituents of blood and their functions Understand the process of hematopoiesis Describe the removal of old red blood cells Describe the symptoms of anemia and its possible causes Define polycythemia and state its causes Given a clinical description, be able to accurately predict its possible cause and explain physiological basis of symptoms Textbook reading: Human Physiology: An Integrated Approach. D.U. Silverthorn (2019) Pearson 8th ed. pages 510-522 (7th ed. 512-523; 6th ed. 545-557; 5th ed. 547-557) Functions of blood • Transports gases, nutrients, hormones and metabolic wastes • Regulates composition of interstitial fluid (e.g. pH, ions, water, etc) • Restricts fluid loss at injury sites via blood clotting • Defends against toxins and pathogens • Regulates body temperature by absorbing and redistributing heat 5 L blood in 70 kg male 4 L blood in 58 kg female Case Study: Erica Fine, a first-year undergraduate student, visited her doctor, complaining of fatigue, irritability, and lightheadedness. Ten years ago, she had been diagnosed with ulcerative colitis. Over the past few months she had omitted animal products from her diet and had eaten only apple sauce for breakfast. 1) List the possible causes of her condition. 2) What tests would you run to make a diagnosis? 3) How would you treat her? The constituents of blood Figure from Martini (2006) Fundamentals of Anatomy and Physiology Hematocrit = % of total blood volume occupied by packed (centrifuged) red blood cells (normal hematocrit = 37-54%) ~Figure 16.1 Plasma 60% 92% 35% 4% Figure 16.1 Most plasma proteins are made by the liver Functions of plasma proteins General: - generate colloid osmotic pressure - buffer pH Specific: Albumins colloid osmotic pressure; carriers Globulins  and b - clotting factors, enzymes, carriers g - antibodies Fibrinogen cleaved to form fibrin in blood clotting ~ Table 16.1 Formed elements 20-40% erythrocytes 99.9% differential white count 2-8% phagocytes leukocytes 0.1% 50-70% thrombocytes 1-4% granulocytes <1% Figure 16.1 Complete blood count results: Erica Fine Hematocrit = 32% (normal women: 37-47%; men 40-54%) Hemoglobin = 10 gm/dl, (normal women:12-16gm/dl; men 14-17gm/dl) WBC = 5.3 X 103/ml (normal: 4-11 X 103) Differential white count is normal Platelets 200 X 103/ml (normal: 150-450 X103/ ml) Copyright © 2010 Pearson Education, Inc. Red blood cells Essentially bags filled with hemoglobin and enzymes ~5 million RBC/ml of blood Figure 16.5 Hemoglobin ~Figure 16.6 Copyright © 2010 Pearson Education, Inc. Brainstorm: What could be the cause of Erica’s low hematocrit? Number of RBC dependent on balanced production and removal Production Removal Normal Make 2-3 million/second Life span about 120 days Production = Erythropoiesis Committed progenitor cell Erythropoietin: hormone made in the kidney Promotes erythropoiesis Produced in response to low oxygen levels which stabilize transcription factor: hypoxia inducible factor (HIF1), thereby, activating transcription of the erythropoietin gene Figure 16.2 Requires: iron, Vitamin B12 and folate in the diet Mature RBC: Anaerobic metabolism No nucleus = no new transcription Hematopoiesis 1:100,000 cells In bone marrow: 25% developing erythrocytes 75% developing leukocytes Figure 16.2 Hematopoiesis—cont’d 2 Figure 16.2 Cytokines regulate hematopoiesis Colony stimulating factors— from endothelial cells and white blood cells Interleukins—from white blood cells Effect: survival, proliferation and differentiation of different cell types Sites of hematopoiesis In embryo: yolk sac, liver, spleen and bone marrow After birth: bone marrow Figure 16.4a Adults: pelvis, spine, ribs, cranium, proximal end long bones What features of Erica’s case might contribute to a low production of erythrocytes? A) Lack of animal products in her diet B) Eating only apple sauce for breakfast C) Her ulcerative colitis D) A and B only E) A, B and C Removal Fe2+ also stored in the liver in ferritin ~Figure 16.6 Silverthorn For information on iron transport: http://www.rcsb.org/pdb/static.do?p=education_discussion/ molecule_of_the_month/pdb35_1.html Figure from Martini (2006) Fundamentals of Anatomy and Physiology Jaundice (hyperbilirubinemia) Bilirubin High turnover of RBC Liver disease Bile duct obstruction http://commons.wikimedia.org/wiki/File:Bil irubin.png What features of Erica’s case might contribute to high removal or loss of erythrocytes? A) Lack of animal products in her diet B) Eating only apple sauce for breakfast C) Her ulcerative colitis D) A and B only E) A, B and C Low production Causes Destruction of stem cells via drugs and radiation (aplastic) Inadequate nutrients: iron, folic acid, Vitamin B12 (nutritional, pernicious) Low erythropoietin (renal) ~ Table 16.3 High removal Causes Hemolytic Genetic: defects in RBC proteins (e.g. hemoglobin) Parasitic infections Drugs (some antibiotics and anti-seizure drugs) Autoimmune reactions Hemorrhagic Excessive blood loss ~ Table 16.3 Erica Fine additional results: Mean Corpuscular volume (MCV) is 74 fl (normal 85-95 fl) Ferritin levels are low No appearance of blood in stool Diagnosis = iron deficiency anemia Polycythemia Hematocrit too high (> ~54%) • high blood viscosity Causes Primary: Abnormal erythrocyte precursors Secondary: Low oxygen delivery to tissues Case study: Leon Leon was doing well in first-year university when he developed a cough and diarrhea. He felt very tired and achy and went to bed early. The next morning he had a severe headache and his neck seemed to be stiff. He went immediately to his doctor. He appeared confused and had a temperature of 39.2C. He had small areas of reddish-purple discoloration on his chest, a red throat and enlarged tonsils. 1) What condition might he be suffering from? 2) Given his enlarged tonsils and fever, he likely has an infection, how does the body fight infection? 3) What is the cause of his fever? Wednesday’s class Immune System--Textbook Reading: 8th ed. 754-767; (7th ed. 754-765; 6th ed. 802-814, 5th ed. 783-793)