51 Effect of physical exercise on laboratory test results

Lothar Röcker, Holger Kiesewetter

Physical exercise is one of the main biological factors with a significant influence on laboratory test results. In many cases, this influence factor is given little notice although it may cause changes in laboratory test results even to abnormal ranges. Misdiagnosis and unnecessary adjunct examinations may result if the physician does not know or take into account his patient’s exercise and training history. For instance, excessive muscle training may cause pronounced increases in creatine kinase.

Physical (endurance) training and acute physical exercise result in blood parameter changes that are not classified under pre-analytical errors because they may include both wanted changes, for example reduced risk factors (blood fats, fibrinogen), and pathophysiological changes such as cell injury. Ideally, separate reference intervals should be defined for the large subpopulation of physically trained individuals. However, because of the lack of such reference intervals, all changes in different laboratory parameters described in this chapter are based on the results of published studies.

Refer to Tab. 51-1 – Markers and their changes after acute and chronic exercise (endurance training).

51.1 Blood and plasma volume

Trans capillary fluid exchange takes place between the intravascular and interstitial spaces. The pores in the capillaries are permeable to water and small molecular weight substances. High molecular weight proteins such as fibrinogen and cellular components such as erythrocytes cannot leave the intravascular space through these pores. In the state of rest, the fluid uptake and discharge are balanced and, consequently, the blood volume is constant.

Even a change in body position (e.g., from supine to standing and vice versa) has a pronounced effect on this equilibrium and causes changes in the plasma volume /1/.

During body exercise, the capillary pressure and surface area increase, causing filtration of fluid into the interstitial space until a new equilibrium has been established. This leads to hemoconcentration of blood components unable to leave the intravascular space. Consequently, the concentration of blood components with a larger diameter than that of the pores in the capillary membrane will increase to the same extent to which the fluid leaves the vascular bed. During acute exercise, the blood volume decreases at the expense of the plasma volume. The plasma volume decreases by 5–20% depending on the duration, intensity, kind of sport and fluid intake /2/.

The plasma volume returns to normal within 30 min. after acute exercise. Overcompensation occurs during the extended recovery phase after endurance exercise, leading to elevated plasma volume that may cause hemodilution and is detectable for several days /3/.

Besides this passive change in blood components induced by fluid movement, physical exercise results in physiological adaptation and immediate changes in blood components. Such functional adaptations may cause significant active changes in the composition of the blood.

Endurance training leads to blood volume expansion under rest conditions /4/. In endurance trained individuals, over proportionate expansion of the plasma volume compared to the red cell volume leading to hemodilution is indicated by low hematocrit and hemoglobin values.

Analysis of changes in the blood components should always take the extent of the given hemoconcentration and/or hemodilution into account. The different blood volume components have different time courses of change. The plasma volume changes fastest /3/. A plasma volume expansion of 10% is already found 24 h after endurance exercise and is detectable for 4 days.

Plasma volume is the first to adapt and expansion usually occurs immediately at the beginning of a training routine of 1–2 weeks /4/. Red cell volume expansion follows after 2–3 weeks until a new equilibrium has been established and is not as pronounced as plasma volume expansion /4/. These changes are considered to be useful adaptations and contribute to the changes in cardiovascular functions (e.g., lower heartbeat rate in trained individuals).

Besides having positive effects, chronic exercise can also cause abnormal conditions such as iron deficiency and cell injury.

51.2 Complete blood count

Erythrocytes

Acute body exercise, especially endurance exercise, causes marked changes in the red blood cell count /5/. The absolute mass of erythrocytes circulating in the blood is determined by erythrocyte formation and degradation. Both processes are so slow that acute influence has no major effect. Therefore, under short-term conditions, the absolute erythrocyte volume is assumed to be constant. Unlike some animals, man has no blood reservoir to deplete in physical exercise /6/. Hence, changes in the red blood cell count during acute exercise are mainly due to hemoconcentration and/or hemodilution.

Hemoconcentration induced by acute physical exercise leads to an increase in hematocrit (HCT), hemoglobin (Hb) and erythrocyte concentrations and the concentration of all high molecular weight substances by approximately 10–30%. These alterations depend on the intensity and duration of exercise. The greatest changes are measured after short physical stress (e.g., after a 200 meter sprint) which causes markedly elevated HCT, Hb and erythrocyte count while the erythrocyte indices remain constant. Levels return back to normal within 30 min. after the sprint.

By contrast, extended endurance exercise like a marathon run has significantly less effect on the red blood cell count. However, the erythrocyte indices may also change in this case; a decrease in MCV points to erythrocytic water loss. Hemodilution is also always observed during extended physical exercise /7/; it causes opposing changes in the erythrocyte count and is detectable for several days.

The erythrocyte count is subject to regulation by erythropoiesis and regulation by the blood volume. Therefore, chronic changes in the red blood cell count largely depend on which of the two mechanisms is stimulated by physical exercise training. Training-induced increase in blood volume is primarily caused by plasma volume expansion.

This leads to the conclusion that hemodilution is already present at rest, at least in endurance-trained individuals. For instance, the red blood cell count values determined in trained individuals are usually below normal /6/.

51.2.1 Hemolysis

Long lasting physical exercise induces an mechanical destruction of erythrocytes and hemolysis. The intravascular hemolysis is due, among other things, to the mechanical compression of red cells in the microcirculation of the foot soles during running. Even hemoglobinuria may occur under certain circumstances /6/. The Hb released from the damaged erythrocytes especially during running binds to haptoglobin in plasma in a 1 : 1 ratio and is degraded in the reticuloendothelial system. Therefore, the haptoglobin concentration is more or less decreased or undetectable after endurance exercise. Based on this mechanism, (21–59) × 10⁹ erythrocytes, corresponding to 5–13 mL of blood, are destroyed during a marathon run /7/.

51.2.2 Reticulocytes

The role of reticulocyte count and calculation of reticulocyte indices is growing in sports medicine, especially in connection with anti-doping monitoring. However, the results depend on the automated analyzers used. The distribution of maturity stages within the reticulocyte population can be determined. The immature reticulocyte fraction is a reliable parameter because it increases before the reticulocyte count /8, 9/.

The bone marrow of athletes is continuously stimulated because of the enhanced iron metabolism. The evaluation of the Hb content of reticulocytes (CHr, Ret-H_e) is crucial because it allows the diagnosis and monitoring of iron deficiency and treatment outcome in a timely manner.

Only a few, partly controversial, studies are available on the changes in reticulocytes following physical exercise. In a study involving marathon runners, elevated reticulocytes were not found until 31 h after the run /10/. After an ultra marathon of six days’ duration, no changes in number and percentage of reticulocytes were found /11/. In a 1,600 km ultra marathon, reticulocyte count elevations were found after 4 and 11 days of running and at the end of the event /12/. The CHr remained constant after an ultra marathon /12/. Since it is also not influenced by the acute phase reaction, it is a useful parameter for monitoring the current quality of erythropoiesis. Therefore, CHr serves as a reliable parameter in clinical tests on iron metabolism in sports medicine. The diagnostic sensitivity of CHr in the assessment of iron deficient erythropoiesis is higher than that of biochemical markers (ferritin, transferrin saturation and the soluble transferrin receptor) /13/.

The number of RNA rich immature reticulocytes indicates hyper proliferative erythropoiesis, as it also does in ineffective erythropoiesis. Immature reticulocytes are elevated in athletes compared to non-athletes and show values above the reference interval /14/.

The CD34⁺ cell is a multi potent progenitor cell [hematopoietic progenitor cell (HPC)] considered to be an indirect measure for hematopoietic activity. Compared to sedentary controls, athletes show a 4-fold increased HPC concentration which decreases again several hours post race /15/. Overall, however, the reticulocyte system shows very little change after endurance exercise.

51.2.3 Pseudoanemia

Care should be taken not to misinterpret subnormal levels of the red blood cell count in endurance athletes as anemia (or sports anemia) as unfortunately happens in some cases. This phenomenon should better be called pseudoanemia /7/. What is important is that this phenomenon is not a disorder, but an adaptation to increased physiological requirements in sports (viscosity, thermoregulation).

51.2.4 Anemia diagnostics in endurance athletes

Athletes, in particular endurance athletes and especially women, can develop anemia independently of the subnormal red blood cell count. However, the evaluation of the red blood cell count in endurance athletes is complicated because changes in the complete blood cell count and in the plasma volume must be taken into account. Therefore, conventional reference intervals for the red blood cell count cannot be used for assessment. A more reliable evaluation is obtained by measuring the erythrocyte mass of the body. The assay methods necessary for this purpose are only offered by specialized institutions. Therefore, the following Hb levels may serve as benchmarks for anemia in athletes /16/:

• Women < 110 g/L
• Men < 130 g/L.

51.2.5 Iron metabolism

Iron deficiency is the most frequently encountered cause of anemia, especially in female endurance athletes. This is because of the increased requirement and consumption of iron in competitive athletes, especially women. Iron deficiency has a negative effect on immune response, temperature regulation, energy metabolism and physical performance. In inflammatory disease, the determination of ferritin is not useful as a marker for diagnosing storage iron deficiency. In the course of an acute phase response, the ferritin concentration measured 3 days after a marathon run is still falsely high in relation to the body iron store. In many cases, endurance athletes show low resting ferritin levels compared to untrained individuals /17/.

Hepcidin

Hepcidin is the body’s systemic iron metabolism regulator /18, 19/. Urinary hepcidin excretion is 4–27-fold increased in two thirds of female marathon runners one day after the race /20, 21/. Hepcidin concentrations are not influenced by sub maximal endurance exercise /22/.

51.2.6 Leukocytes

In acute exercise, the leukocyte count shows more pronounced changes than the red cell count that cannot be explained by changes in the plasma volume alone. Physical exercise of different intensities was found to induce substantial leukocytosis /23/. In high intensity physical activity, the leukocyte count can be twice as high as the resting level (in individual cases up to 31.8 × 10⁹/L given a baseline of 6.4 × 10⁹/L). After 30 minutes exercise, leukocyte count returns to normal within half an hour.

The leukocytes increase by 50–100% (neutrophils, lymphocytes) immediately after endurance exercise. After 30 min., the lymphocytes for 3–6 h decline to levels 30–50% below those before exercise. At the same time, pronounced, prolonged neutrophilia is observed. In leukocyte response post endurance exercise, this results in a bi-phase pattern with another peak reached 2–4 h post-exercise. Catecholamines and the consecutively increased cardiac output are responsible for early leukocytosis causing the marginal stores to be depleted from leukocytes whereas cortisol is thought to trigger the later phase by releasing leukocytes from the bone marrow. These leukocytoses are detectable for at least 8 h and can last for more than 24 h in some cases.

There are no unequivocal findings regarding the different types of leukocytes. Neutrophilia, lymphocytosis and eosinopenia are found to occur. Monocytes are mildly elevated and basophilic granulocytes are slightly decreased.

Only a few studies on chronic changes in the white blood cell count of athletes are available. There is no difference in the magnitude of leukocyte response to acute exercise between untrained and trained individuals. Trained athletes are assumed to have slightly lower leukocyte levels /24/.

Lymphocyte sub populations

Physical activity and exercise have a significant effect on the number of leukocytes and function of lymphocyte sub populations. Among the three major lymphocyte sub populations (T, B and NK cells), the NK cells show the strongest response. Increases to 150–400% typically occur during and immediately after the exercise /25/. After 1 h post exercise, a long-term suppression of levels far below the baseline before the exercise takes place. Seven days after 120 minute endurance exercise, the NK cells are still decreased by 40% /26/. The number of CD8⁺T cells increases by 50–100%, whereas the count of CD4⁺T cells and B cells remains relatively unaffected. The concentration of CD8⁺T cells increases more strongly than that of the CD4⁺T cells, thus causing a reduction in the CD4⁺/CD8⁺T cell ratio to 50% /25/. The reduced ratio is thought to be of clinical significance. In severe exhaustion, it can lead to an ’open window’ with an increased risk of upper respiratory tract infection. This phase lasts for 3–72 h after strenuous exercise /27/.

There are controversial references regarding chronic changes in lymphocyte sub populations. In some cases, the resting numbers of cells seem to be significantly decreased in trained versus untrained individuals. This applies to numerous types of sports.

51.2.7 Thrombocytes

At rest, circulating platelets are discoid in shape. Various studies found an increase in platelet count after exercise /28/. The increase is attributed to the release of platelets from vessels in the spleen, bone marrow and lung and quickly returns to normal. The effects of training on the platelet count have only been investigated in a few studies to date. Athletes have a much less pronounced increase in platelet counts and show quick normalization compared to sedentary individuals. Decreased activation of stimulated platelets has been reported in individuals after twelve-month training. Daily training results in reduced platelet activity at rest /28/.

51.3 Hemostatic system

Prothrombin time

No changes are found after strenuous prolonged exertion /29/.

Activated partial thromboplastin time (aPTT)

The aPTT is significantly shorter in short term, medium term and long term endurance exercise, and also still 3 h after a marathon run. In particular, the activity of FVIII among the individual factors of the intrinsic activation pathway is increased in physical exercise /29/ with a concurrent equivalent increase in von Willebrand factor (vWF). In addition, changes in the normal vWF multimer pattern following endurance exercise have been reported /30/.

Fibrinogen

Different results have been obtained regarding the level of fibrinogen in physical exercise. The majority of studies do not find any changes in the fibrinogen concentration; some publications describe increases or decreases.

One day after a marathon run, immunologic measurement showed increases in fibrinogen concentrations from 233 mg/dL to 279 mg/dL, presumably due to stress-related acute phase response /31/. Fibrinogen is useful as an independent risk indicator for cardiovascular disease. Longitudinal studies have documented a beneficial effect of regular endurance exercise on the fibrinogen concentration. The average decrease achieved is around 40 mg/dL /32/.

Prothrombin fragment (F1 + F2)

F1 and F2 increase under both sub maximal and maximal ergometric exercise /33/.

Thrombin-antithrombin complex (TAT)

Increased TAT concentrations are measured after short-term maximal exercise. The changes can be interpreted as increased thrombin formation. Elevated fibrinopeptide A was found after endurance exercise and fibrin monomers were detected in individual cases /29/.

Training and coagulation

Little information is available concerning the effect of training on coagulation. Cross-sectional comparisons do not show any difference in aPTT in seemingly healthy joggers, marathon runners and untrained individuals, neither at rest nor following strenuous exertion. However, findings are completely different in patients with coronary disease. Exercise appears to have an inhibitory effect on coagulation. The aPTT is prolonged after several training bouts. Four-week training in the cardiac rehabilitation exercise group already results in decreased FVIII activity while healthy controls do not show any changes.

51.4 Fibrinolytic system

Determination of the euglobulin lysis time is the standard screening test for in vitro hyper fibrinolysis following exercise. The euglobulin lysis time is significantly shorter and the concentration of the degradation product B (peptide 15–42) increases after a marathon run. The D-dimer concentration is also significantly increased. D-dimers are considered to be specific fibrin degradation products.

The tissue plasminogen activator (t-PA) located in the vascular endothelium is an important regulator of fibrinolysis. Under exercise, plasminogen activators are released from the vascular endothelium, causing increased fibrinolytic activity. The effect of cycle ergometer exercise under aerobic metabolic conditions on fibrinolytic activity (t-PA, D-dimers) is much smaller than after moderate exercise followed by short-term maximal exercise in the anaerobic range /33/. Under exercise, the released t-PA appears not to be fully blocked by inhibitors because t-PA activity surges after exercise in the anaerobic range.

The plasminogen activator inhibitor (PAI) activity declines during ergometric exercise, presumably because the inhibitor is exhausted. After a marathon run, the t-PA activity increases approximately 30-fold and returns to baseline after 3 h. The t-PA concentration increases 5-fold; PAI activity is not detectable after the marathon run. The t-PA concentration is about equally as high after short term maximum cycle ergometer exercise as after a marathon run /29, 33/.

It can generally be stated that exercise training results in increased coagulability in healthy individuals on the one hand and activated inhibitor potential as well as over proportionate activation of the fibrinolytic system, on the other. Thus, thromboembolism is not to be expected. The hemostatic equilibrium in healthy individuals has merely adapted to a higher level. However, the recovery phase following endurance exercise includes a time window with increased coagulability because coagulation is activated longer than fibrinolysis. This phase is characterized by an increased risk of thrombosis and may lead to thromboembolic events in risk patients.

Although it is uncontroversial that physical activity contributes to a reduction in cardiovascular risk, the causality has not been elucidated and is still subject to speculation. Physical training seems to have a positive effect on fibrinolysis. No changes in PAI-1 activity were found in 132 individuals before and three years after a moderate training program. However, a subpopulation consisting of homozygotes for the 4G allele of 4G/5G polymorphism in the promoter of the PAI-1 gene showed a 36% reduction in PAI-1 activity. Thus, regular exercise within the scope of a training program may be effective for such individuals /34/.

In summary, the investigations in this field have shown that no consistent effect of physical training on the fibrinolytic system can be recognized. On the contrary, numerous factors play a role such as the intensity of the training program, the analyzed population and the analytical methods used, although an increase in fibrinolytic activity is very likely.

51.5 Serum enzymes

In trained, but especially in untrained individuals, acute exercise can result in elevated serum enzyme levels that may last for hours to days /5/. The elevations predominantly involve enzymes originating from the skeletal muscles (CK, AST, LD), which, due to changed permeability of the muscle fiber membrane or due to muscle injury, are released to the blood to an increased extent.

In some cases, enzyme elevations are caused by rhabdomyolysis. Endurance exercise and high intensity muscle activity can lead to injury, especially in untrained or atypically stressed myocytes. Consequently, cytoplasmic enzymes such as CK, CK-MB, LD, AST and proteins like myoglobin are released from the cell and their serum activity increases /35/. Due to the extremely high concentration gradient of CK of 500,000 : 1 between the muscle cell and the blood, CK is especially sensitive to high intensity muscle work.

Liver specific enzymes can also be elevated under strenuous physical activity. The elevation is due to the increased permeability of the hepatocyte membrane because of decreased hepatic blood flow and decreased hepatic oxygen saturation.

Products such as H₂O₂ from polymorphonuclear neutrophils are thought to be responsible for changes in the cell membrane under exercise /36/. The plasma indicators CK-MM, CK-MB, AST, LD, ALP and aldolase were increased after a marathon run /37/. CK-MM, CK-MB, aldolase and AST rose further 12 h after the race. CK-MM, CK-MB, AST and ALT remained elevated 3 h after the marathon; aldolase, LD and alkaline phosphatase returned to pre-race levels 7 days after the marathon /37/. The increase in enzyme activity depends on the intensity and duration of exercise and is highest in untrained individuals.

Physical exercise causes changes in the muscle cells. The size, number and surface of mitochondria increase depending on the kind of training and fitness level. Moreover, the production of intracellular enzymes and, thus, their concentration in the blood increases /38/. The pattern of change in CK differs in trained versus untrained individuals. Resting CK values are higher in trained individuals, while in untrained individuals, CK increases progressively for up to 5 days after acute exercise. The peak values measured can be 33-fold the baseline levels.

In contrast, the CK level in trained individuals is only elevated for 24 h after the exercise, reaching a peak of 2.3 times larger than the pre-exercise level /39/. Athletes have higher resting CK-MB values than non athletes. The sport specific reference intervals for CK (2.5th and 97.5th percentiles) are 47–513 U/L in female athletes and 82–1,083 U/L in male athletes /40/.

Statin associated myopathy increases pronouncedly with physical activity /41/.

Symptoms of myocardial infarction in athletes are a difficult diagnostic challenge to the physician because troponin I is also elevated, but remains far below the pathologic range of conventional troponin tests /42/.

In a study using a highly sensitive cardiac troponin (cTnT) assay, 28% of the marathon runners were positive for cTnT pre-race. Post race, all runners had detectable TnT values. In 94% of these cTnT positive runners, the level exceeded the 99th percentile of cardiac healthy individuals /43/.

51.6 Serum lipids

The concentration of serum lipids changes in acute exercise depending on hemoconcentration or hemodilution.

Under endurance exercise, lipolysis increases the availability of lipids for energy production, resulting in a decrease in triglycerides by half that is detectable up to 3 days after the exercise. In particular, enhanced lipolysis causes markedly increased concentrations of glycerin and free fatty acids in the blood /5/. Lp(a) does not change in response to acute exercise /44/.

A mild increase in HDL cholesterol and a tendentiously mild decrease in LDL cholesterol is found after acute endurance exercise /45/. Endurance training has a beneficial effect on the lipid metabolism /46/.

Aerobic training results in elevated HDL cholesterol and decreased VLDL and LDL cholesterol as well as decreased triglycerides.

Modifications of apolipoproteins in endurance trained athletes include increased Apo A-1 and decreased Apo B. Changes in the other apolipoproteins [Apo A-II, C-II, C-III, E, Apo(a)] are usually not detected /46/. The lipoprotein profile is more strongly influenced by training duration than by training intensity. The increase in HDL cholesterol primarily involves the HDL₂ fraction /47/. However, there exists great variability as a function of genetic factors.

51.7 Renal function

Strenuous exercise causes reduced renal blood flow depending on the exercise intensity. Following exhausting ergometer exercise, the renal blood flow decreases by 53.4% immediately after exercise and remains decreased to 82.5% 30 min. and to 78.9% 60 min. after exercise in comparison with the resting value /48/. This transitory impairment of renal function results from an increase in urea, creatinine and uric acid in serum and, under unfavorable conditions, can lead to severe renal complications /49/. During a marathon run, the urea and uric acid concentrations can increase by 53% and 42%, respectively, and remain elevated for 24 h. In all athletes, the urea/creatinine ratio is above 40, indicating pre renal azotemia which is also detectable 24 h after exercise. The increase in creatinine by 20.5% suggests a 18% decrease in creatinine clearance according to the Cockroft and Gault formula. The creatinine increase presumably results from creatine release from working muscles, dehydration and/or reduction in renal perfusion and the glomerular filtration rate.

Cystatin C levels are less biased by marathon running than creatinine concentrations /50/. Cystatin C was elevated in 26% and creatinine in 46% of the runners. The mean cystatin C increase was twice as low as compared to creatinine (21% and 41%, respectively).

Urinary protein excretion increases under physical exertion. This phenomenon is reversible, but is an interference factor in the interpretation of renal proteinuria. Moderate exertion such as recreational sport can already induce tubular and, to a small extent also, glomerular proteinuria /51/.

Very few studies exist concerning chronic changes in athletes. Changes are thought to be fully reversible or, in very rare cases, may have pathophysiological consequences. Athletes generally show higher resting urea concentrations, presumably due to continuous training.

51.8 Other blood components

Plasma osmolality is one of the most tightly regulated physiological variables.

51.8.1 Sodium

The serum Na⁺ concentration depends on the water metabolism. Therefore, the most frequently encountered cause of abnormal Na⁺ concentrations is water deficiency or excess.

Moderate or short term exercise causes no, or only slight, changes in the Na⁺ concentration.

Under endurance exercise, hyponatremia is not uncommon, especially in women, depending on the ambient temperature, loss of fluid and fluid intake.

Hyponatremia is the most common complication in ultra endurance sports but is usually asymptomatic (130–134 mmol/L). Athletes with severe hyponatremia with concentrations below 130 mmol/L are symptomatic in most cases. The incidence of hyponatremia in athletes requiring treatment after a marathon run is reported as 23% /52/.

Healthy marathon runners can develop non cardiogenic pulmonary edema associated with elevated intracranial pressure and hyponatremic encephalopathy. The condition may be fatal if undiagnosed, while appropriately treated patients recover again.

51.8.2 Potassium

The K⁺ content of the skeletal muscles decreases under physical activity. K⁺ released from the muscle cells accumulates to elevated concentrations in the blood but quickly returns to normal. Increased uptake from the blood of K⁺ by the muscle cells can cause mild hypokalemia /53/.

51.8.3 Calcium

The Ca²⁺ level in the blood remains unchanged although the calcium metabolism is affected by physical training. In acute exercise, hemoconcentration causes a transient increase in Ca²⁺ concentration due to the partial binding of Ca²⁺ to high molecular weight proteins. The number of studies available on the relationship between exercise and Ca²⁺ is insufficient to make a final assessment.

51.8.4 Magnesium

Mg²⁺ is the second most common cation in the body after K⁺. A transient decrease in plasma Mg²⁺ concentration due to a shift of Mg²⁺ into the erythrocytes is found after endurance exercise. Mg²⁺ deficiency is more common in endurance trained athletes than in non-endurance trained individuals. The deficiency is caused by increased renal Mg²⁺ excretion /54/.

51.8.5 Zinc

Zn is involved in muscle energy metabolism, protein synthesis and infection protection. Competitive athletes and heavy workers may suffer from Zn deficiency, affecting 23% of female and 43% of male participants in the study with serum Zn concentrations below the reference interval of 75 ng/dL (11.4 μmol/L). Increased losses of Zn are caused by heavy perspiration, urinary excretion and a catabolic metabolic condition after physical exercise.

51.8.6 Glucose

Increased influx of glucose from the blood into the muscle cells may occur after physical activity depending on the intensity and duration of exercise. At the same time, glucose is supplied to the blood, primarily by hepatic glycogenolysis, until a steady-state glucose concentration in the blood is reached. However, the glycogenolysis can only be maintained for a limited time depending on the amount of the glycogen reserves /55/. Consequently, after prolonged physical exercise (about one hour), the glucose level in the blood decreases to 70% of the pre-exercise level. In many cases, however, the glucose concentration remains decreased for a relatively long time after prolonged physical exercise because of the continued uptake of glucose by the muscle cells /55/. The long lasting decrease in glucose concentration is influenced by adrenalin (insulin antagonist), which is no longer released after exhausting physical exertion, causing the insulin effect to become predominant and enhancing hypoglycemia approximately 2 h after the end of the physical activity.

The decrease in glucose level due to physical exertion is especially pronounced in high glucose concentrations (diabetics) /55/. Although there is a significant difference between the glucose metabolism in trained versus untrained individuals, glucose concentrations are not different. However, glucose homeostasis is more constant in trained individuals. Sixteen weeks of high intensity training in adults with type 2 diabetes resulted in reduced HbA_1c levels from 8.7% to 7.6% and reduced the dose of medication. The non diabetic control group showed no change in HbA_1c values /56/.

51.8.7 C-reactive protein (CRP)

Strenuous physical activity within 2–6 h results in an increase in pro-inflammatory and anti-inflammatory cytokines due to muscle damage. The interleukin-6 concentration increases up to 100-fold after a marathon run. CRP levels above 10 mg/L are measured after endurance exercise (especially running). These levels are only reached with a delay during the extended recovery phase (after approximately 24 h) and return to normal within a few days /57/.

Whereas acute physical exercise results in a delayed increase in CRP depending on the fitness level, regular training reduces resting CRP levels. CRP measured under resting conditions before and after 9 months of endurance training (preparation for a marathon run) decreased from 1.19 mg/L to 0.82 mg/L. A control group did not show any changes during this period /58/.

51.8.8 Blood viscosity

Blood viscosity is determined by plasma viscosity, hematocrit (HCT) and mechanical properties of red blood cells. Plasma viscosity limits the blood flow in the supply capillaries where the HCT value is only approximately 15%. Plasma viscosity is a measure for perfusion and the hydrogenation condition given a specified pressure gradient and geometry of the terminal vessels. Despite its great significance, plasma viscosity is not measured in most laboratories. Acute physical activity, independently of its intensity, affects the rheological properties of blood by increasing blood viscosity which is mainly attributed to an increase in HCT and plasma viscosity.

Physical training causes favorable changes in some rheological blood factors, in particular reduced blood viscosity and reduced aggregability of the red blood cells. This effect is important because increased blood viscosity may have significant pathological consequences. HCT above 0.60 and plasma viscosity above 4 mPas are cutoff values for the occurrence of symptoms in healthy individuals /59/. In patients with atherosclerotic vessels, HCTs above 0.48 and plasma viscosities above 1.6 mPas can already trigger acute symptoms. It should be noted when considering the favorable effects of training that overtraining can result in an early increase in blood viscosity /60/.

References

1. Röcker L, Schmidt HM, Junge B, Hoffmeister H. Orthostasebedingte Fehler bei Laboratoriumsbefunden. Med Labor 1975; 28: 267–75.

2. Röcker L, Heyduck B. Hämatologische Veränderungen bei körperlichen Leistungen. GIT Labor-Medizin 1986; 7: 405–9.

3. Gillen CM, Lee R, Mack GW, Tomasell T, Nishiyasu T, Nadel ER. Plasma volume expansion in humans after a single intense exercise protocol. J Appl Physiol 1991; 71: 1914–20.

4. Sawka MN, Convertino VA, Eichner ER, Schneider SM, Young AJ. Blood volume: importance and adaptations to exercise training, environmental stress, and trauma/sickness. Med Sci Sports Exerc 2000; 32: 332–48.

5. Herbert C, Meixner F, Wiebking C, Gilg V. Regular physical activity, short-term exercise, mental health, and well-being among university students: The results of an online and a laboratory study. Front Psychol 2020; 11: 509. doi: 10.3389/fpsyg.2020.00509. eCollection 2020.

6. Röcker L, Laniado M, Kirsch K. The effect of physical exercise on plasma volume and red blood cell mass. In: Dunn CDR (ed). Current concepts in erythropoiesis. Chichester: John Wiley & Sons Ltd 1983; 245–77.

7. Röcker L, Röcker C. „Sportanämie“ – wieviel Blut kostet ein Marathonlauf. J Lab Med 1999; 23: 6–10.

8. Banfi G, Mauri C, Morelli B, Di Gaetano N, Malgeri U, Melegati G. Reticulocyte count, mean reticulocyte volume, immature reticulocyte fraction, and mean sphered cell volume in elite athletes: reference values and comparison with the general population. Clin Chem Lab Med 2006; 44: 616–22.

9. Banfi G, Fabbro M, et al. Behaviour of reticulocyte counts and immature reticulocyte fraction during a competitive season in élite athletes of four different sports. Int Jnl Lab Hem 2007; 29: 127–31.

10. Schwandt HJ, Heyduck B, Gunga HC, Röcker L. Influence of prolonged physical exercise on the erythropoietin concentration in blood. Eur J Appl Physiol 1991; 63: 463–6.

11. Fallon KE, Bishop G. Changes in erythropoiesis assessed by reticulocyte parameters during ultralong distance running. Clin J Sport Med 2002; 12: 172–8.

12. Fallon KE, Sivyer et al. Changes in haematological parameters and iron metabolism associated with a 1600 kilometre ultramarathon. Br J Sports Med 1999; 33: 27–32.

13. Thomas C, Thomas L. Biochemical markers and hematologic indices in the diagnosis of functional iron deficiency. Clin Chem 2002; 48: 1066–76.

14. Banfi G, Roi GS, Dolci A, Susta D. Behaviour of haematological parameters in athletes performing marathon and ultramarathon in altitude (“skyrunners”). Clin Lab Haematol 2004; 26: 373–7.

15. Bonsignore MR, Morici G, Santoro A et al. Circulating hematopoietic progenitor cells in runners. J App Physiol 2002; 93: 1691–7.

16. Eichner ER. The anemias of athletes. Physician Sportmed 1986; 14: 122–30.

17. Schumacher YO, Schmidt A, König D, Berg A. Effects of exercise on soluble transferrin receptor and other variables of the iron status. Br J Sports Med 2002; 36: 195–200.

18. Camaschella C, Nai A, Silvestri L. Iron metabolism and iron disorders revisited in the hepcidin era. Haematologica 2020, 105 (2): 260–72.

19. Hugman A. Hepcidin: an important new regulator of iron homeostasis. Clin Lab Haem 2006; 28: 75–83.

20. Roecker L, Meier-Buttermilch R, Brechtel L, Nemeth E, Ganz T. Iron-regulatory protein hepcidin is increased in female athletes after a marathon. Eur J Appl Physiol 2005; 95: 569–71.

21. Peeling P,Dawson B, Goodman C. Athletic induced iron deficiency: new insights into the role of inflammation, cytokines and hormones. Eur J Appl Physiol 2008; 103: 381–91.

22. Troadec M-B, Lairie F, Daniel V, Rochongar P, Ropert M, Cabillic F, et al. Daily regulation of serum and urinary hepcidin is not influenced by submaximal cycling exercise in humans with normal iron metabolism. Eur J Appl Physiol 2009; 106: 435–8.

23. McCarthy DA, Dale MM. The leucocytosis of exercise. A review and model. Sports Med 1988; 6: 333–8.

24. Ndon JA, Snyder AC, Foster C, Wehrenberg WB. Effects of chronic intense exercise training on the leukocyte response to acute exercise. Int J Sports Med 1992; 13: 176–82.

25. Rowbottom DG, Green KJ. Acute exercise effects on the immune system. Med Sci Sports Exerc 2000; 32: 396–405.

26. Shek PN, Sabiston BH, Buguet A, Radomski MW. Strenuous exercise and immunological changes: a multiple time-point analysis of leukocyte subsets, CD4/CD8 ratio, immunoglobulin production and NK cell response. Int J Sports Med 1995; 16: 466–75.

27. Pedersen BK, Hoffman-Goetz L. Exercise and the immune system: Regulation, integration and adaptation. Physiol Rev 2000; 80: 1055–81.

28. Wang JS, Jen CJ, Kung HC, Lin LJ, Hsiue TR, Chen HI. Different effects of strenuous exercise and moderate exercise on platelet function in men. Circulation 1994; 90: 2877–85.

29. Röcker L, Drygas WK, Heyduck B. Blood platelet activation and increase in thrombin activity following a marathon race. Eur J Appl Physiol 1986; 55: 374–80.

30. Rock G, Tittley P, Pipe A. Coagulation factor changes following endurance exercise. Clin J Sport Med 1997; 7: 94–9.

31. Schobersberger W, Wirleitner B, Puschendorf B, Koller A, Villinger B, Frey W, Mair J. Influence of an ultramarathon race at moderate altitude on coagulation and fibrinolysis. Fibrinolysis 1996; 10: 37–42.

32. Ernst E. Regular exercise reduces fibrinogen levels: a review of longitudinal studies. Br J Sports Med 1993; 27: 175–6.

33. Röcker L, Möckel M, Westpfahl WKP, Gunga HC. Influence of maximal ergometric exercise on endothelin concentrations in relation to molecular markers of the hemostatic system. Thromb Haemost 1996; 75: 612–6.

34. Väisänen SB, Humphries SE, Luong LA, Penttilä I, Bouchard C, Rauramaa R. Regular exercise, plasminogen activator inhibitor-1 (PAI-1) activity and the 4G/5G promoter polymorphism in the PAI-1 gene. Thromb Haemos 1999; 82: 1117–20.

35. Aigner A, Ledl-Kurkowski E, Dalus E, Schmid I, Gibitz HJ. Serumspiegel von kardialem Troponin-T, Kreatinkinase und CK-MB nach Langzeit-Ausdauerbelastungen. Dt Z Sportmed 1994; 45: 136–40.

36. Fielding RA, Violan MA, Svetkey L, Abad LW, Manfredi TJ, Cosmas A, Bean J. Effects of prior exercise on eccentric exercise-induced neutrophilia and enzyme release. Med Sci Sports Exerc 2000; 32: 359–64.

37. Lijnen P, Hespel P, Fagard R, Lysens R, Eynde EV, Goris M, et al. Indicators of cell breakdown in plasma of men during and after a marathon race. Int J Sports Med 1988; 9: 108–13.

38. Keul J, Berg A, Lehmann M, Chaves RS. Enzymadaptation im Muskel durch Training. Dt Zeitschr Sportmed 1982; 12: 403–7.

39. Pedersen BK. Exercise and cytokines. Immunol Cell Bio 2000; 78: 532–5.

40. Mougios V. Reference intervals for serum creatine kinase in athletes. Br J Sports Med 2007;41: 674–8.

41. Meador BM. Statin-associated myopathy and its exacerbation with exercise. Muscle&Nerve 2010

42. Gerth J, Ott U, Fünfstück R, Bartsch R, Keil E, Schubert K, et al. The effects of prolonged physical exercise on renal function, electrolyte balance and muscle cell breakdown. Clin Nephrol 2002; 57: 425–31.

43. Saravia SG, Knebel F, Schroeckh S, Ziebig R, Lun A, Weimann A, Haberland A, et al. Cardiac Troponin T release and inflammation demonstrated in marathon runners. Clin Lab 2010; 56: 51–8.

44. Hubinger L, Mackinnon LT, Barber L, McCosker J, Howard A, Lepre F. Acute effects of treadmill running on lipoprotein (a) levels in males and females. Med Sci Sports Exerc 1997; 29: 436–42.

45. Berg A, Keul J. Beeinflussung der Serumlipoproteine durch körperliche Aktivität. Dtsch Ärztebl 1984; 81: 1161–7.

46. Berg A, Halle M, Baumstark M, Frey I, Keul J. Einfluß und Wirkweise der körperlichen Aktivität auf den Lipid- und Lipoproteinstoffwechsel. Dtsch Z Sportmedizin 1991; 42: 224–31.

47. Leon AS, Gaskill SE, Rice T, Bergeron J, Gagnon J, Rao DC, et al. Variability in the response of HDL cholesterol to exercise training in the HERITAGE family study. Int J Sports Med 2002; 23: 1–9.

48. Zuzuki M, Sudoh M, Matsubara S, Kawakami K, Shiota M, Ikawa S. Changes in renal blood flow measured by radionuclide angiography following exhausting exercise in humans. Eur J Appl Physiol 1996; 74: 1–7.

49. Neumayr G, Pfister R, Hoertnagel H, Mitterbauer G, Getzner W, Ulmer H, et al. The effect of marathon cycling on renal function. Int J Sports Med 2003; 24: 131–7.

50. Mingels A, Jacobs L, Kleijnen V, Wodzig W, Dieljen-Visser M. Cystatin C a marker for renal function after exercise. Int J Sports Med 2009: 30: 668–71.

51. Boege F, Rieger Y, Schardt F. Belastungsproteinurie als Störfaktor in der Interpretation renaler Proteinurieformen. Lab med 1992; 16: 101–4.

52. Speedy DB, Noakes TD, Rogers IR, Thompson JMD, Campbell RGD, Kuttner JA, et al. Hyponatremia in ultradistance triathletes. Med Sci Sports Exerc 1999; 31: 809–15.

53. Sejersted OM, Medbo/ JI. Muscle and plasma electrolyte during exercise. Int J Sports Med 1989; 10: 98–100.

54. Saur P, Joneleit M, Tölke H, Pudel V, Niedmann PD, Kettler D. Evaluation des Magnesium-Status bei Ausdauersportlern. Dtsch Z Sportmed 2002; 53: 72–8.

55. Hughes DC, Ellefsen S, Bar K. Adaptations to endurance and strength training. Cold Spring Harb Perspect Med 2018; 8 (6): a029769. doi: 10.1101/cshperspect.a029769.

56. Castaneda C, Layne JE, Munos-Orian L, Gordon PL, Walsmith J, Roubenoff R, et al. A randomized controlled trial of resistance exercise training improve glycemic control in older adults with type 2 diabetes. Diabetes Care 2002; 25: 2335–41.

57. Gabriel HHW, Müller HJ, Kindermann W. Die Akute-Phase-Reaktion. Deutsche Zeitschrift für Sportmedizin 2000; 51: 31–2.

58. Mattusch F, Dufaux B. Reduction of the plasma concentration of C-reactive protein. Int J Sports Med 2000; 51: 21–4.

59. Kiesewetter H. Bedeutung der Blutfluidität für den Allgemeinarzt. Z f Allgemeinmedizin 1989; 65: 425–8.

60. El-Sayed MS, Ali N, El-Sayed AZ. Haemorheology in exercise and training. Sports Med 2005; 35: 649–70.