Blood, Haemoglobin, and Oxygen Transfer

Blood, haemoglobin, and oxygen transfer Learning Objectives • • • • • • • • Understand why multicellular organisms face different challenges for survival than unicellular organisms Know the basic functions of the respiratory system, the relationship between structure and function, and its fundamental role in supporting cell activity elsewhere in the body Know the basic functions of the cardiovascular system in the transport of oxygen, and its fundamental role in supporting cell activity elsewhere in the body. Describe the main constituents and functions of blood Draw a normal oxyhaemoglobin dissociation curve and identify the normal arterial and mixed venous points. Explain how oxygen is transported to cells of the body via attachment to haemoglobin in red cells. Give normal values for haematocrit, haemoglobin, blood volume, arterial oxygen saturation and oxygen content. Identify that without a nucleus, red cells cannot make new enzymes or replace damaged haemoglobin and components of their membranes. What do cells need to survive? • • Chemical building blocks Carbohydrates, Protein, Lipids (Fats, oils, waxes, steroids), Nucleic Acids Energy sources - Molecules ‘burn’ to make energy Oxygen The mitochondrion • • • • • First discovered in the nineteenth century, and was dubbed ‘bioblast’ Requires pyruvic acid (made from glucose in cytoplasm), free fatty acids or amino acids Needs O2 Makes the energy currency used in cells, ATP (Adenosine Triphosphate) Makes waste product (CO2) Why being one cell big is helpful • • Oxygen need only diffuse a short distance from the cell membrane to where it is needed Carbon dioxide need only diffuse a short distance to exit the cell • • Absorb small molecules from their environment Ingest ‘food’ by engulfing a smaller creature and digesting them in an internal vacuole Mechanism for efficiently taking in O2 and excreting CO2 (Respiratory System) • • • Tubes to carry gases in and out of body Numerous diffusing chambers (alveoli) with thin membranes, close to small blood vessels, so O2 can diffuse into the blood and CO2 can diffuse out A bellow mechanism to suck air in, and expel it with waste gases How the bellows work • • During Inspiration, the volume of the chest cavity increases due to active Elevation of the ribs and Contraction (downward flattening) of diaphragm During Expiration, the volume of the chest cavity decreases due to passive Relaxation (upward bulging) of diaphragm Ribs return to normal position 11 < 50 % -- Surface tension of water-air interface >50% Cells making up the alveolus (functional unit of the lung) • • • • • • Type I cells, which are very thin squamous cells that form most of the wall of the alveolus and across which oxygen diffuses. Type II cells, which secrete surfactant. Macrophages, which enter the alveoli from the blood. Fibroblasts, which are found in the interstitial. Capillary (squamous) endothelial cells, which carry blood around the periphery of each alveolus. For clarity in the diagram, the thicknesses of the type I cells and the capillary endothelial cells are exaggerated by about 3X. The actual distance gas must diffuse between the alveolar airspace and blood for the most part is less than about 0.5 µm. Surface Tension Surfactant (a critical concept) Lung of a baby with hyaline membrane disease (not enough surfactant) Comparative chest x-rays The Circulation: an engineering rationale • • • Larger organisms have both a reduced surface area to volume ratio & need to transport substances over greater distances. Diffusion is distance limited Some vital substances, e.g., Oxygen are poorly soluble in water.˙. Need a specialised transport system. The Circulation: an engineering design analysis REQUIREMENTS: 1. 2. Pump - Heart Energy source for pump - Intrinsic combustion of O2 /nutrients 3. Pipes to/from appropriate points - arteries & veins to/from all organs 4. Interface/exchange systems - (A) Lung. - (B) Tissue capillaries 5. An appropriate fluid – BLOOD FUNCTIONS OF BLOOD • • • • • • • Oxygen transport Nutrient transport Carbon dioxide transport Waste product transport Humeral messaging (hormone transport) Counter infection/immunological roles Systemic/self-repair – i.e., coagulation Components of blood The green topped tube contains mixed whole blood The white topped tube has been centrifuged into 3 layers: • • • Top – plasma Middle - “buffy coat” of white cells & platelets. (In the tube it appears bigger than it really is as it also contains a separating gel) Bottom: red blood cells. They have a higher density due to their iron content, so settle to the bottom. BLOOD CONSTITUENTS PLASMA: • • Water & salts – i.e., ECF (isotonic* fluid) Proteins – roles include: – Transport - e.g., albumin (carries free fatty acids & other lipid soluble compounds) Immunoglobulins Coagulation (& fibrinolytic) factors Oncotic pressure CELLULAR • • • - Erythrocytes* A.k.a red blood cell Oxygen carriers Leukocytes A.k.a white blood cell Five types Inflammatory and immune roles Platelets Cellular fragments Clot formers Blood: The numbers • • • • • • - Blood volume ≈ 5L or 70mls/kg ≈ 3L plasma (≈ 65g/L plasma proteins) ≈ 2L red cells (4-6 billion per ml) Haematocrit* ≈ 40% White cells: 3-10 million per ml Platelets: 150-400 million per ml Vital role in haemostasis* & coagulation* The clotting cascade Erythrocytes (Red Cells) • • • • ≈ 25,000,000,000,000 in a 70kg adult Produced in bone marrow Skull, vertebrae, sternum, ribs, pelvis in adult Also, femur & tibia in adolescent/child Predominantly by liver & spleen in fetus By division from stem cells Stimulated by erythropoetin* Erythrocytes (Red blood cells) “Flying saucers of the bloodstream” • • • • • Disc shaped: 8 μm (microns) x 2.5 μm Lifespan 100-120 days (normal cell) Destroyed by macrophages in spleen No nucleus, mitochondria or endoplasmic reticulum (ER) in mature RBCs This means Glycolytic* metabolism only • Maintenance of discoid shape requires energy So why does it? It maximises surface area & minimises distance to enhance diffusion of oxygen Erythrocytes (Red blood cells) II "A bag of red goodies” • Contains • haemoglobin* (Hb) • 25% of cytoplasmic volume is Hb • This equates to ≈ 340g/L • Oxyhaemoglobin has a red colour. • Deoxyhaemoglobin has a blue-ish colour – cyanosis “Haemoglobin: Smarter than your average protein” Heterotetramer: Adult form • 2 Alpha chains - Goblin fold (ά helix) Porphyrin ring Central Fe2+ ion • 2 Beta chains - Goblin fold (ά helix) Porphyrin ring Central Fe ion Infants • 2 α chains • 2 γ chains Haemoglobin • Oxygen carrying compound • Contains iron within heme* molecule • 4 heme + 4 peptide chains (2α, 2β) → 1x haemoglobin (Hb) • Carries 1 molecule O2 per heme molecule • i.e., 4 x O2 per Hb compound unit • = 1.34 mls O2 per gram of Hb Oxygen & Haemoglobin • O2 binding depends on pO2 - partial pressure* of oxygen • Oxygen carriage not linear but sigmoid* • This is the “Oxy-haemoglobin dissociation curve Arterial saturation Max 9798% Mixed venous (at rest) (Venous blood returning to heart) P02 40 mmHg 75% Saturated ➔ ‘reserve’ capacity at rest P50 = 27 mmHg Haemoglobin again But who is “R”? Under most normal circumstances the value of “R” is around 0.8 – and this value is accepted in most physiological calculations. So: • Oxygen consumption in the “physiological” 70kg male is about 250mls/min • Multiplied by “R” gives us his CO2 production. • i.e. 250 x 0.8 = 200mls (or ~0.4 grams) CO2 /min