Ch. 6 Gas Transport by the Blood Oxygen Carried in the blood in 2 forms o Dissolved in plasma o Bound to Hb in RBC Henry’s Law: Amt. of dissolved O2 is relative to the partial pressure O2 content = 1.35 (Hb) (O2 Sat.) + 0.003 (PaO2) o 18.7 = 1.35 (14)(.975) + 0.003 (100) --- Normal o Note: west uses 1.39 for this, 1.35 is avg. of difft. Literature o West says normal O2 content of blood is about 20.8 ml O2 per 100 ml blood Hemoglobin 4 polypeptide chains; 2 alpha, 2 beta Hb A: Normal adult Hb o Normal ferrous (2+) iron can be oxidized to ferric (3+) form by various drugs o Ferric Hb = methemoglobin toxic effects Hb F: infant Hb (gradually replaced over 1st year) Hb S: sickle cell (has valine substituted for glutamic acid in beta chains) o Hb S results in a right shift of dissociation curve Deoxygenated form crystallizes in the RBC thrombus Anemic pt w/ Hb conc. Of 10g per 100 ml blood, w/ PO2 of 100 mm Hg O2 dissociation curve Capacity: max amt. that O2 that Hb can carry (i.e. 4 x O2 per 1 molecule of Hb) O2 saturation: o ( O2 combined with Hb / O2 capacity ) x 100 o Normal O2 saturation of 97.5% w/ a PaO2 of 100 mm Hg Change in Hb from saturated state to unsaturated state (deoxy) is accompanied by conformational change in molecule Oxygenated form = R state (relaxed) Deoxygenated form = T state (tense) Sigmoidal curve means: o Flat upper portion – so even if PAO2 drops some, no biggie o Diffusion process is increased d/t difference of partial pressure of O2 b/t alveoli and cap o Steep lower part of curve means that peripheral tissues can withdraw large amounts of O2 for only a small drop in capillary PO2 Cyanosis: reduced Hb is purple – low arterial O2 saturation Right Shift Caused by: (increased tissue metabolism increased O2 unloading) o Increased: temp, CO2, DPG, H+ o Decreased: pH Left Shift Caused by: (i.e. cooling down a trauma victim to reduce O2 unloading) o Increased: pH o Decreased: temp, CO2, DPG, H+ o Carbon Monoxide DPG – metabolite of glycolytic pathway; increased by chronic hypoxia, altitude, chronic lung disease Bohr Effect: at lower pH, O2 will bind to Hb with lower affinity PO2 (50%) – 27 mm Hg ((normal)) [increased in rt. Shift, or decreased in lt. shift] Carbon Monoxide (CO) o Irreversibly (essentially) binds to Hb and forms carboxyhemoglobin (COHb) o Little goes a long way: PCO of 0.16 mm Hg = 75% Hb bound as COHb o Shifts curve to left Oxygen Dissociation Curve o PO2: 100 (arterial) o SO2: 97% (arterial) o PO2: 40 (from tissues) o SO2: 75% (from tissues) Carbon Dioxide CO2 Carried as: dissolved, bicarbonate (HCO3), combo w/ proteins (carbamino compounds) Normal = 24 mmol/L Dissolved CO2: obey’s Henry’s Law o Henry’s Law: At a constant temperature, the amount of a given gas dissolved in a given type and volume of liquid is directly proportional to the partial pressure of that gas in equilibrium with that liquid o About 20 times more soluble than O2 Bicarbonate Prod’n (HCO2) o Main form of CO2 in blood o CO2 + H2O <-> H2CO3 <-> H+ + HCO2 o HCO2: bicarbonate o H2CO3: carbonic acid o Carbonic anhydrase: converts CO2 + H2O H2CO3 o H+ cannot easily diffuse out of RBC Chloride Shift: To maintain neutrality in RBC, Cl- ions diffuse into the RBC from plasma Some of H+ ions liberated are bound to reduced Hb o H+ + HbO2 <-> H+ ∙Hb + O2 Haldane Effect: the fact that deoxygenation of the blood increases its ability to carry CO2 o The lower the saturation of Hb with O2, the larger the CO2 concentration for a given PCO2 Uptake of CO2 by RBC increases osmolarity and therefore water enters cell, increasing Vol. Carbamino compounds: o Formed by combination of CO2 with terminal amine groups in blood proteins o Most important protein: globin in Hb o Hb ∙ NH2 + CO2 <-> Hb∙NH∙COOH o Reduced Hb can bind more CO2 as carbamino Hb CO2 dissociation curve Linear relationship (steeper) PaCO2 = PACO2 Normal Ranges: 38-42 mm Hg CO2 is carried as: dissolved, bicarbonate, carbamino CO2 curve is right-shifted by increases in Saturation of O2 Acid-Base Status Lungs excrete huge amounts of carbonic acid (via CO2 and H2O) Altering alveolar ventilation and thus elimination of CO2, the body has greater control over acidbase balance Normal pH = 7.4 Hb acts as a buffer If plasma bicarbonate concentration is altered by the kidney, the buffer is less effective o Base Excess: Increase in bicarbonate conc. o Base deficit: reduced bicarbonate conc. Respiratory Acidosis Caused by an increase in PCO2 which reduces HCO3-/PCO2 ratio decrease pH If respiratory acidosis persists, kidney responds by conserving HCO3- (d/t increased PCO2) Henderson Hassselbach: o pH = 6.1 + log [(bicarbonate- mmol/L) / 0.03 x 60] Respiratory Alkalosis caused by a decrease in PCO2 o can be d/t: hyperventilation, high altitude Metabolic Acidosis ratio of HCO3- to PCO2 falls decrease in pH can be d/t DM, lactic acid increase in respiration acts to increase CO2 (le’ chatlier principle) o stimulus is H+ ions in peripheral chemoreceptors Metabolic Alkalosis increase in HCO3 raises the HCO3/PCO2 ratio and pH increases can be d/t loss of gastric acid secretion, secretion by vomiting, reduction of alveolar ventilation that raises PCO2 4 types of acid base disturbances o pH = pK + log (HCO3- / 0.03 x PCO2) Acidosis Primary Compensation o Respiratory PCO2 ++ HCO3- ++ o Metabolic HCO3 -PCO2 – Alkalosis o Respiratory PCO2 -HCO3 – o Metabolic HCO3 ++ n/c Blood- Tissue Gas Exchange d/t diffusion proportional to tissue area and difference in gas partial pressure b/t 2 sides inversely proportional to thickness thickness of BGB is < 0.5 µm distance b/t open capillaries in resting muscle 50 µm during exercise additional cap’s open, reducing the diffusion distance and increasing the area for diffusion CO2 diffuses x20 faster than O2; therefore O2 deliver is more difficult than CO2 removal Critical situation: the intercapillary distance or the O2 consumption where PO2 = 0 mm Hg Purpose of much higher PO2 in capillary blood is to ensure an adequate pressure for diffusion of O2 to the mitochondria o At sites of O2 utilization the PO2 is very low (( i.e. why O2 leaves RBC for low pressure in mito)) Hypoxia: abnormally low PO2 in tissue o Can be measured by cardiac output x arterial O2 conc. o Q(dot) x CaO2 Tissue Hypoxia can be d/t: o A low PaO2 (hypoxic hypoxia or, hypoxemia) o Reduced ability of blood to carry O2 as in anemia or CO poisoning (anemic hypoxia) o Reduction in tissue blood flow i.e. hemorrhagic shock (circulatory hypoxia) o Cyanide (f’s up ETC) – (hystotoxic hypoxia) Refer to 6-1 table for more info