Effect of Smoking on Tissue Oxygen Supply

TL;DR

In nine healthy young male smokers (>1 pack/day), chronic CO exposure was associated with increased red cell mass and higher hemoglobin/hematocrit/red cell count, plus lower P50 and ATP but unchanged DPG, compared with 18 nonsmokers. The authors conclude smoking causes mild erythrocytosis consistent with tissue hypoxia from decreased oxygen-carrying capacity and increased oxygen-hemoglobin affinity, without intraerythrocytic adaptation.

Key findings

• Smokers had mean carboxyhemoglobin (COHb) of 6.2% vs 1.0% in nonsmokers; eight of nine smokers had morning COHb between 4% and 6.8%, and one who smoked 2–3 packs/day had 9.2%.
• Peripheral blood values were higher in smokers: mean hematocrit 47.4% vs 45%, hemoglobin 16.6 vs 15.7 g/100 ml, red cell count 5.50 vs 5.08 × 10⁶/cu mm, and white count 7457 ± 1119 vs 5838 ± 1076/cu mm; platelet and reticulocyte counts were similar.
• Red cell mass was significantly greater in smokers: mean 31.8 vs 28.6 ml/kg, 1321 vs 1132 ml/sq m, and 14.9 vs 12.0 ml/cm (P < 0.05, < 0.001, < 0.001). Six of nine smokers had red cell mass >1300 ml/sq m vs 1 of 18 nonsmokers. One smoker with COHb 9.2% had red cell mass 1581 ml/sq m (37.6 ml/kg), which fell to 1381 ml/sq m (33 ml/kg) after 3 months of cessation, with hematocrit falling from 50% to 47% and to 45% at 6 months.
• Oxygen-hemoglobin affinity and red cell phosphates: mean P50 was 23.1 mm Hg in smokers vs 24.2 mm Hg in nonsmokers; red cell ATP was 4.50 vs 5.15 µmoles/g Hb; mean DPG was 12.7 µmoles/g Hb in both groups.

Methods

• Twenty-seven healthy white men aged 20–32 participated: 9 smokers of one or more packs/day and 18 nonsmokers of similar age, sex, and race; no subject had donated blood in the prior 6 months.
• From the same morning venous blood sample, the study measured blood counts, red cell ATP, DPG, COHb, and oxygen-hemoglobin curves; red cell mass was measured with a radioactive chromium method and expressed per kg, per cm of height, and per sq m. Arterial blood gases were measured on brachial artery blood.
• Oxygen-hemoglobin dissociation curves were determined spectrophotometrically using a tonometer cuvette, with P50 based on at least five points. Reliability testing found a 1 mm Hg shift in P50 per 5% COHb over the 5%–20% COHb range.

Limitations

• The paper states that no correction was made for plasma trapping in red cell mass measurements, that morning COHb values represent minimum levels, and that further studies are necessary to determine the importance of smoking as a primary cause of spurious erythrocytosis.
• Evident from the text: the sample was small (9 smokers, 18 controls) and all subjects were healthy white men aged 20–32, so findings may not generalize to women, older adults, nonwhite individuals, or patients with anemia, heart disease, chronic lung disease, or cerebrovascular disease—groups the authors only suggest may be at risk.
• Evident from the text: the design was cross-sectional except for one cessation case, and the smokers had significantly higher mean weight (82.3 kg vs 73.6 kg) despite slightly lower mean height; the paper notes the red cell mass difference would be more striking if expressed per lean body mass.