Week 6 Resp II Lecture PDF

Resp II Lecture October 23, 2023 - 9:23 AM For each hb, has 4 sites for binding O2 Rbc lasts 3 months Thus looking at a1c, will vary every 3 months Normal adult Hb: HbA has 2 alpha and 2 beta chains HbA2: 2 alpha and 2 delta Most adults have 1-3% of HbA2, but 97% HbA Fetal Hb: 2alpha and 2 gamma...

Resp II Lecture October 23, 2023 - 9:23 AM For each hb, has 4 sites for binding O2 Rbc lasts 3 months Thus looking at a1c, will vary every 3 months Normal adult Hb: HbA has 2 alpha and 2 beta chains HbA2: 2 alpha and 2 delta Most adults have 1-3% of HbA2, but 97% HbA Fetal Hb: 2alpha and 2 gamma (HbF), as fetus gets closer to term, will make HbA - Week 6 Page 1 If only 3/4 sites saturated, then 75% saturated; 2/4 = 50% saturation - Newborn already starting to make HbA, but doesn't have same proportions? Week 6 Page 2 Newborn already starting to make HbA, but doesn't have same proportions? - - alpha chain stays stabilized, with normal Hb production Gamma chain (fetal Hb is high in utero, and goes away at birth) Beta chain rises after birth Delta chain is only a small %, and after 1 year it will be the same as adulthood proportions Problems with hb pathies, ex. Sickle cell anemia--> b/c fetus is fine with fetal Hb, thus we can turn ON fetal Hb production and not make as much sickle cell Hb to prevent complications of newborn. Suppressing inappropropriate Hb production - Not same as HbA - Under stress or unique conditions, it will not stay in the flexible biconcave disc, and will sickle, causing point parts of Hb, and will not go well through capillaries and will collect and aggregate and form clots = Vaso occlusive crisis, anything distal to clot forms infarcts to tissue Week 6 Page 3 - Normal beta chain, one of them has been changed in sickle cell - Glutamic acid changes to valine, and valine has a hydrophobic component to it (doesn't like water), but the plasma is made of water - So under stress, the hydrophobic component tries to condense the rbc, causing sickling of cell - Cardiogenesis: at 3wks GA, start to develop heart in chambers, and most of the chambers aren't fully developed until 8 weeks. Will usually send pregnant women for dating U/S and estimate how far along they are. If dating US is done earlier, (6 weeks GA), stressful if patient doesn't hear the heartbeat. Thus better to send these pts at or after 8 weeks - Fetal circulation: umbilical cord--2 arteries and 1 vein, but umbilical vein has highest level of O2, and arteries are deoxygenated blood. (similar to pulmonary veins and arteries). - Holes in fetal circulation to promote blood to flow through systemic circulation - Ductus Venosus - takes blood directly from umbilical vein to IVC, bypassing liver to avoid metabolism of nutrients - Foramen Ovale - R and L atrial connection, O2 coming from placenta, so ok to bypass pulmonary system. turns to fossa ovalis after birth. - Ductus arteriosus - connection between pul art and aorta, bypassing pul system, and gets quickly to systemic circulation Week 6 Page 4 to systemic circulation Week 6 Page 5 - Each pathway of blood turns into_________ after first breath? Crying helps to inflate lungs Prior to this, fluid in lungs and no need to oxygenate fetal Hb, but now need alveoli to work Helps to dec lung pressure, to enable air to enter lower pressure in lungs Dec pressure in RA and RV, to help promote blood flow throughout circulation. R side heart should have lower blood pressure - Fossa ovalis closure can be complete only after 1 year, so some times have atrial septal defect. We don't worry unless complicates fetal development - Inc O2 concentration will constrict ductus arteriosus, and will turn into the ligamentum, and all blood will flow through pulmonary system - Week 6 Page 6 blood will flow through pulmonary system - After birth need to establish good blood flow through circulation - So having a good cry is good for development - A quick whimper and then going to sleep is worse - Small percent is dissolved in plasma O2 has poor solubility coefficient, thus need a way to transport it via Hb There is a reversible reaction: deoxyHb and add O2 in lungs will become oxyhb and generation H+ ion In tissues, it will dissociate and O2 and go into tissues Week 6 Page 7 - Diff binding sites for Hb - Looks at relationship of what's happening to binding sites in relation to PO2 and then there are external factors that can shift the curve to L or R - Normal PO2 at tissue level is 40mmHg, and in cells, the Hb is 75% saturated with O2 - Most times, there is a large reserve of O2 - In lungs, pO2 is anywhere between 80-100mmHg and the Hb is 98% saturated with O2 - As you move down O2-Hb dissociation curve, as the PO2 drops, the Hb will become radically less saturated Week 6 Page 8 - BPG (enzyme) aka DPG These factors can shift curve to L or R When curve is L shifted, the O2 has tighter binding to Hb, so the O2 stays on the Hb R shift of the curve means the O2 gets released "the L stays "left" ON" vs. "R gets Released" - - With low pH, more H+ ions, more metabolism in body, the saturation curve drops and saturation drops from 50% to 38%. So oxygen is more readily released to meet the O2 demands of body - With higher pH, pO2 65%, and shifting curve to L, the O2 gets left on Week 6 Page 9 - High Co2, Atp waste product, want O2 to be released, so curve shifts to R - Low CO2, want O2 to stay left on, curve shifted to L - With high temp, O2 saturation decreases, and will shift to R Week 6 Page 10 - With high temp, O2 saturation decreases, and will shift to R - ex. Fever, want to release O2 to body to help deal with inflammatory response - Low temp, O2 saturation increases - In affinity, tightness high between O2 and Hb, shift to L - Shift to R, dec affinity, O2 released more easily - 2,3DPG/BPG, and enzyme found in rbcs, so hormones can inc level of enzyme increased in rbc, can shift curve to R, and low levels will shift to L Week 6 Page 11 - Works with the alpha and gamma chains - There is far less BPG enzyme in fetal Hb, so it will shift the fetal Hb curve to L naturally - Thus with higher concentration of fetal Hb compared to normal adult Hb, it will shift the curve to L Carbon Monoxide: - CO binds to the same sites as O2, but if have both mocs, the CO moc binds 200x tighter than O2 (greater preference for CO than O2) - pCO, at 0.4p, almost completely saturated the Hb moc ~ 100% - Ex. With CO poisoning, will present with cherry red lips, O2Sat probe reflects how many of those Hb sites are bound, doesn't tell us if those sites are bound with O2 or CO? so CO poisoning will show 100% saturation ○ Treat: bombard with O2, rebreather mask use Week 6 Page 12 - Up to now, covering what's been happening at sea -level, not alveolar level - With Hb level > 100 is good - If Hb is < 50 or pts with cardiovascular or resp disease, will give packed rbcs, b/c need more Hb circulation - Normal people, may let Hb go down to 70s, but lower than this, think about how they are coping - For CVS and resp pts, will assess when Hb is below 80s - CO2 has higher solubility in plasma - 23% gets combined with Hb - Bringing CO2 from tissues to lungs Week 6 Page 13 ***know this equation** - Most of CO2 transport happens this way ^ - Carbonic anhydrase is a catalytic enzyme, speeds up a reaction, quickly puts CO2 and water to make an acid and then dissociates to H+ ion and bicarbonate ion - In rbcs, there is a high amount of carbonic anhydrase, so it promotes this reaction - O2 being loaded on rbc, when putting on O2, it pushes CO2 off = Haldane effect - When CO2 comes on, will facilitate O2 coming off = Bohr effect Week 6 Page 14 At the level of the lungs: - O2 comes into rbc, and binds with deoxyHb, and get H ion formation (red arrow) - With H+ ion formation, pushes CO2 to alveoli (blue arrow) - small amount uses this reaction in plasma, but no carbonic anhydrase b/c none in the plasma, so very slow reaction - Chloride shift: bicarb comes into rbc and the chloride goes out ---know that it exists, but don't need to know more than this Week 6 Page 15 - Better picture of what's happening Week 6 Page 16 Better picture of what's happening At the level of the tissues: - Bohr effect: as CO2 comes in(blue arrow), and O2 goes off (red arrow) - and get H+ ion, which will push the O2 off the Hb within the rbc - There will be a chloride shift b/c bicarb goes out and chloride comes in (reverse shift) Week 6 Page 17 - b/c of H ion, O2 is pushed off the Hb and makes it deoxyHb - Don't need to know these numbers Week 6 Page 18 - 21% * 760 = 160 = 160 PO2 in air at sea level In higher altitudes, the atmospheric pressure decreases, but composition remains the same Fraction of O2 is still 21%, but when the atmospheric pressure is low, the pO2 is lower As you elevate the pO2 decreases With 160 pO2 in air at sea level, towards the alveoli the pO2 is lower and close to 100 If starting at PO2 of 134, the alveoli may get even lower than PO2 of 100 Looking at O2 saturation curve, if shift to the L, the pO2 decreases and won't be fully saturated Week 6 Page 19 - As we move up in elevation, the pO2 decreases - When climbing, need to bring O2 canisters, and will need to use it at higher points - Below sea level, the pO2 increases as you go deeper - High levels of pO2 can be toxic, and can destroy lung tissue with the free radicals that are produced - Problematic for infants, who are more sensitive to high O2 levels, b/c can lead to lung damage and scarring etc Week 6 Page 20 - As you go under, dec thoracic cavity, and increases the pressures - With diving, Inc pressure, and pO2 will be higher - Every other gas in mixture is equally increasing their partial pressure, b/c every gas acts on its Week 6 Page 21 - Every other gas in mixture is equally increasing their partial pressure, b/c every gas acts on its own, so individually working - With diving, N makes up 79-80% of air, and it will dramatically inc its pressure, upwards to 4000 mmHg - When you put any gas at high pressure, it will become soluble, so at these pressures, nitrogen will become soluble in the blood, thus with diving, need to elevate slowly - Can go down slowly, and MORE IMPORTANT to go up slowly, to prevent nitrogen gas from turning into bubbles and an air embolus forming, leading to death - So coming up slowly, you gradually dec nitrogen pressure, allowing it to revert back to gas in the lungs, until you come back up to sea level - Not going to be tested on this** Week 6 Page 22