Respiratory Physiology PDF - Summer 2024

RESPIRATORY PHYSIOLOGY 4. Gas transport in the blood Andre Azevedo, DVM, MSc Assistant Professor of Veterinary Physiology [email protected] Gas transport Pearson Education  Oxygen transport...

RESPIRATORY PHYSIOLOGY 4. Gas transport in the blood Andre Azevedo, DVM, MSc Assistant Professor of Veterinary Physiology [email protected] Gas transport Pearson Education  Oxygen transport Oxygen is poorly soluble in water/plasma – carried in 2 forms in blood Dissolved – 2% Normal tissue need: 5 ml/dL O2 dissolved: 0.3 ml/dL Produces partial pressure (drives O2 bound: 20.1 ml/dL diffusion). O2 bound to hemoglobin does not contribute to PaO2 Insufficient do meet tissue demands Bound to hemoglobin – 98% https://drrajivdesaimd.com/2015/08/24/pulse-oximetry/  Oxygen transport Hemoglobin - Globular protein with 4 subunits – each contains: Heme molecule – iron-binding protoporphyrin, produced by mitochondria https://www.britannica.com/science/hemoglobin Globin chain – polypeptide designated either alpha (α) or beta (β), produced by ribosomes A single red blood cell contains 270 million molecules of hemoglobin https://www.rcsb.org/3d-view/1GZX/1 https://en.wikipedia.org/wiki/Hemoglobin#/media/File:1GZX_Haemoglobin.png  Oxygen transport The type and sequence of amino acids that compose globin are critical to oxygen binding Heme is a protoporphyrin consisting of four pyrroles with a ferrous iron (Fe2+) at the center Each ferrous iron can combine reversibly with a single molecule of O2 Without the presence of globin, oxygen would irreversibly oxidize the ferrous iron (Fe2+) to ferric iron (Fe3+) The amino acids in globin cradle the heme and limit the access of O2 to the ferrous iron, preventing oxidation, allowing uptake and release of oxygen in response to local PO2 An enzyme called METHEMOGLOBIN REDUCTASE is located inside red blood cells and also helps keeping iron in its reduced state  Oxygen transport The type and sequence of amino acids that compose globin define the different types of mammalian hemoglobin Adult hemoglobin (HgA) – contains 2 alpha and 2 beta chains Fetal hemoglobin (HgF) – contains 2 alpha and 2 gamma chains HgF has higher affinity for O2, facilitating O2 movement from the mother to the fetus 2,3-BPG (2,3-bisphosphoglycerate) binds to HgA and reduces its oxygen affinity, but it doesn’t bind strongly to HgF. Usually replaced by HgA in the first year of life https://pdb101.rcsb.org/motm/257  Oxygen transport A molecule of hemoglobin can reversibly combine with 4 molecules of oxygen When hemoglobin is deoxygenated is called DEOXYHEMOGLOBIN – 0% saturation When oxygenated is called OXYHEMOGLOBIN individually can vary saturation levels - 25% - 50% - 75% - 100% (fully saturated) heme-heme interactions increase/decrease affinity for O2 as hemoglobin saturates/desaturates POSITIVE COOPERATIVITY https://ib.bioninja.com.au/options/option-d-human-physiology/d6-transport-of-respiratory/oxygen-dissociation-curve.html  Oxygen transport Cyanosis results from increased desaturated hemoglobin https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6463781/ https://medizzy.com/feed/32715046 https://heartsmart.vet.tufts.edu/difficulty-breathing-dyspnea/ Oxyhemoglobin dissociation curve amountofoxygen Cunningham's Textbook of Veterinary Physiology, 6th Edition Cunningham's Textbook of Veterinary Physiology, 6th Edition  Oxyhemoglobin dissociation curve https://ib.bioninja.com.au/options/option-d-human-physiology/d6-transport-of-respiratory/oxygen-dissociation-curve.html  Oxygen transport Oxyhemoglobin dissociation curve Saturation does not increase linearly as PO2 increases Heme-heme interactions affecting affinity (positive cooperativity) are responsible for the sigmoidal shape Increase steeply as PO2 increases from 0 to 40 mmHg, levels off between 50 and 100 mmHg, where most of the hemoglobin is saturated Change in affinity – binding of first molecule to a heme increases affinity for the second one, and so forth Under normal conditions, on average, only a single O2 molecule is removed from each hemoglobin to satisfy the tissues’ need for O2.  Oxygen transport 4 O2 bound to Hb -> oxyhemoglobin fully saturated -> highest affinity How is O2 released to the tissues?  Oxygen transport Factors affecting O2 affinity: Temperature pH PCO2 2,3-BPG Concentration 50% P50 = 30 mmHg Produces changes in P50, shifting the curve to the 30 42 left or to the right Cunningham's Textbook of Veterinary Physiology, 6th Edition pso cosaturation sot rewatch  Oxygen transport Factors affecting O2 affinity: Temperature temp pH pH PCO2 PLOz RIGHT SHIFT (decreased affinity) 2,3-BPG Concentration 2,3 BPG 50% higher temp lower pH higher PCO2 Right shift – easier O2 release P50 = 30 mmHg higher [2,3-BPG] in high metabolic areas (the tissues) 30 42 Cunningham's Textbook of Veterinary Physiology, 6th Edition  LEFT SHIFT (increased affinity) Oxygen transport lower temp higher pH lower PCO2 Factors affecting O2 affinity: lower [2,3-BPG] Temperature temp pH pH PCO2 PLO2 RIGHT SHIFT (decreased affinity) 2,3-BPG Concentration 2,3BPG 50% higher temp lower pH higher PCO2 Right shift – easier O2 release P50 = 30 mmHg higher [2,3-BPG] in high metabolic areas (the tissues) 21 30 42 Left shift – more difficult O2 release in areas with low metabolic demand Cunningham's Textbook of Veterinary Physiology, 6th Edition  Oxygen transport Right shift – occur when there is decreased affinity of Hb to oxygen P50 increase – need higher PO2 to reach 50% of saturation Cunningham's Textbook of Veterinary Physiology, 6th Edition Decreased affinity = O2 release facilitated High metabolic rate areas (need oxygen): high PCO2 high temperature low pH high 2,3-BPG – byproduct of glycolysis in RBCs, increases during hypoxic conditions  Oxygen transport Left shift – occur when there is increased affinity of Hb to oxygen P50 decrease – need lower PO2 to reach 50% of saturation Cunningham's Textbook of Veterinary Physiology, 6th Edition Increased affinity = O2 release more difficult Low oxygen demand areas: low PCO2 low temperature high pH low 2,3-BPG  Carbon dioxide transport CO2 is carried in the blood in three forms: 23% carried in RBCs bound to hemoglobin (carbaminohemoglobin) 70% dissolved in plasma as bicarbonate 7% free, dissolved in plasma https://teachmephysiology.com/respiratory-system/gas-exchange/transport-carbon-dioxide-blood/  Carbon dioxide transport CO2 carried bound to hemoglobin Carbon dioxide reacts directly with amino radicals (-NH) of the hemoglobin molecule to form carbaminohemoglobin CO2 does not bind to the same position where O2 binds Reversible reaction, driven by PCO2 CO2 is easily released in the lungs where PCO2 is lower There are other carbamino proteins in the plasma, transporting CO2 the same way (