HCO - 3 H 2 CO 3 CO 2 + H H H + Breathing rate is regulated by blood ph and C02. CO2 and Bicarbonate act as a ph Buffer in the blood

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Breathing rate is regulated by blood ph and C02 breathing reduces plasma [CO2]; plasma [CO2] increases breathing. When C02 levels are high, breating rate increases to blow off C02 In low C02 conditions, CO2 is easily blown off, so breathing rate does not change (even if O2 levels are dangerously low) Examples: 1. breathing into a sealed container -> decreased O2, increased CO2 in the container -> faster, deeper breathing as body tries to blow off excess CO2 2. breathing into a sealed container with CO2 filter -> decreased O2, but no CO2 in the container -> normal breathing, because brain does not detect elevated CO2 -> until body runs out of O2 3. pilots at high altitude: low O2, low CO2 Jonathan Miller, The Body in Question, part 4 (6/6) (youtube: X3dDQQcWhyU) CO2 and Bicarbonate act as a ph Buffer in the blood Buffer - a chemical added to a solution to keep the ph constant by preventing rapid changes in [H + ] As acid is added to a buffer, it absorbs the new [H + ]. ---> so little or no change in ph As base is added to a buffer, it gives up [H + ] to replace the ones sucked up by the base. ---> so little or no change in ph C + H 2 0 Carbonic acid H 2 CO 3 Bicarbonate HCO - 3 + H + If blood ph is too high (basic) breathe less to retain C : more C -> more bicarbonate + more H + -> more acid If blood ph is too low (acidic) breathe more to blow off C : less C -> less bicarbonate + less H + -> less acid Bicarbonate: The natural buffer in the blood Carbonic acid C + H 2 0 H 2 CO 3 Bicarbonate HCO - 3 + H + if ph, then need more H + C + H 2 0 H 2 CO 3 HCO 3 - + H + C + H 2 0 H 2 CO 3 HCO 3 - + H + C + H 2 0 H 2 CO 3 HCO 3 - + H + So if blood ph rises (more basic), keep C -- don t breathe out

if ph, then need to absorb more H + CO2 + H 2 0 H 2 CO 3 HCO 3 - + H + C + H 2 0 H 2 CO 3 HCO 3 - + H + C + H 2 0 H 2 CO 3 HCO 3 - + H + So if blood ph drops (more acidic), breath off C ph and Breathing If blood ph is too high (basic) breathe less to retain C : more C -> more bicarbonate + more H + -> more acidic If blood ph is too low (acidic) breathe more to blow off C : less C -> less bicarbonate + less H + -> less acidic Figure 16.40 carbonic anhydrase enzyme

Chemoreceptors in: Medulla <- low ph <- C Carotid Bodies Aortic Bodies <- low ph <- hi C <- low <- low ph <- hi C Figure 16.25 Figure 16.29 carbonic anhydrase carbonic acid bicarbonate

Table 16.6 Figure 16.28

Acidosis: blood ph < 7.34 Alkalosis: blood ph > 7.45 Respiratory acidosis/alkalosis: changes in CO2 and HCO3 due to hyperventilation or hypoventilation. Metabolic acidosis/alkalosis: changes in blood ph or HCO3 due to physiological effect or disease; can be partially corrected by ventilation. Hemoglobin and Hemoglobin Dissociation Curves Transport of CO2 Respiratory Challenge: Fetus In Utero (in the uterus) Hemoglobin Respiratory pigment that picks up oxygen from lungs, releases oxygen into tissues: increases oxygen carrying capacity of blood Consists of 4 protein subunits (2 x alpha, 2 x beta subunits) and 4 heme molecules (centered around iron atom that binds O2 molecule). Iron gives blood reddish hue. oxyhemoglobin: when carrying oxygen; deoxyhemoglobin: when not carrying oxygen. Dissociation curve: proportion of hemoglobin that is carrying oxygen as a function of oxygen concentration in the blood (or as a function of ph, or temperature, etc.) Hemoglobin associates with oxygen at high oxygen concentrations (in lungs); oxygen dissociates from hemoglobin at low oxygen concentrations (in tissues). Bohr Shift: oxygen dissociates from hemoglobin at low ph (reflects high CO2 in tissues). 2,3 DPG: molecule that is produced when oxyhemoglobin low; causes more oxygen release from hemoglobin. hemo- blood globin - protein

Dissolved O2 Content of Blood Henry s Law: [O2] ml/l = 0.031 x PO2 at PO2 in lungs = 100 mmhg [O2] in blood = 3.0ml/L So maximum total oxygen in human blood (5 L) = 3.0 ml/l x 5 L blood = 150 ml O2 (dissolved) but human uses 250 ml O2 per minute. Figure 16.32 Figure 16.31

O 2 O O2 2 O2 O2 Hb O2 Lungs P O2 = 100 Tissue P O2 = 40 O2 O 2 O O2 2 O2 Hb Lungs P O2 = 100 Tissue P O2 = 40 O2 Content of Oxyhemoglobin in Blood [O2] bound to saturated oxyhemoglobin = 1.36 ml/g Hb [Hb] = 150 g / L of blood So total O2 in human blood (5 L) 1.36 ml O2 / g Hb x 150 g Hb / L x 5 L blood = 1020 ml O2 Total O2 = 150 ml dissolved O2 + 1020 ml O2-Hb human uses 250 ml O2 per minute; so hemoglobin provides a large reserve of O2

Hemoglobin Dissociation curve Amount of O2 unloaded to exercising tissues Exercising Figure 16.33 Bohr Shift: oxygen dissociates from hemoglobin at low ph (high CO2 in tissues). At PO2 = 35 mmhg: at ph 7.4: 68% oxyhemoglobin at ph 7.2: 52% oxyhemoglobin therefore, more O2 unloaded at ph 7.2 Figure 16.34 Figure 16.35 Glucose ATP lactate

Myoglobin Respiratory pigment in skeletal and cardiac muscle cells. Similar to hemoglobin, but only 1 heme molecule. Stores oxygen in muscle cells, helps transfer oxygen from blood to muscle mitochondria. Dissociation curve for myoglobin is shifted to the left: only unloads oxygen at very low oxygen levels (during exercise). In heart muscle, myoglobin stores oxygen for use during systole, when coronary arteries are squeezed shut by contraction. Myoglobin in the blood indicates damage to muscle tissue. Myoglobin Hemoglobin Figure 16.37 Myoglobin optimized for Low Oxygen Conditions

Carbon Dioxide transport Carbon Dioxide is transported in the blood as: dissolved CO2 (7% of blood CO2) carbaminohemoglobin (20% of blood CO2) bicarbonate ion (HCO3 ) In Tissue Capillaries: Carbonic Anhydrase in red blood cells catalyzes H2CO3 formation. H+ binds to deoxyhemoglobin, HCO3 is exchanged for Cl- ion from plasma (chloride shift) In Pulmonary Capillaries: Reverse chloride shift exchanges Cl- ion to bring HCO3- into red blood cell. Oxyhemoglobin releases H+, so H2CO3 -> CO2 is formed and diffuses into lungs. Carbon Monoxide poisoning CO also binds hemoglobin, but binding is irreversible (210x higher than ). Binding of 50-80% of hemoglobin is fatal. Victims of CO poisoning are cherry red, because of carboxyhemoglobin color. Figure 16.38 Figure 16.39

Figure 16.42 PO2 below 50 mm Hg stimulates O2 chemoreceptors Fetal Circulation Placenta: Gas (and nutrient) exchange in high-surface area capillary bed between mom and fetus Fetal Hemoglobin binds more O2 in low-o2 environment of placenta Circulation of blood through umbilical cord to placenta to exchange gases. Shunts in fetal heart to send O2 rich blood directly from vena cava to left atrium (oval foramen) and to aorta (ductus arteriosus) so that lungs are bypassed

umbilical cord Figure 20.48 Fetal Hemoglobin : binds oxygen better in lower oxygen condition of placenta

Fetal Circulation http://www.lpch.org/diseasehealthinfo/healthlibrary/hrnewborn/0181-pop.html Ductus Arteriosus Shunt connects pulmonary artery to aorta (bypassing lungs) Oval Foramen Shunt connects right atrium to left atrium (bypassing lungs) from placenta http://macomb-rspt.com/files/rspt1210 /MODULE%20A/Fetal%20Circulation.jpg to placenta http://www.chop.edu/healthinfo/patent-ductus-arteriosus-pda.html

see Figure 13.14 http://www.chop.edu/healthinfo/patent-ductus-arteriosus-pda.html