Viktig studie som viser hvor mye CO2 økes når pustefrekvensen halveres. Om normal pust er 15 bpm økes CO2 fra 35 til 40 mmHg når pustefrekvensen går ned til 8 bpm.
http://journal.publications.chestnet.org/article.aspx?articleid=1082916#t2
http://www.ncbi.nlm.nih.gov/pubmed/15539726/
Nevner mye viktig om oksygen metning og oximetri. Sier at den normal intracellulære oxygenmetninger er 40 mmHG, som er en SpO2 på 80%.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2662504/
A useful caveat is to memorize the significance of 2 saturation readings; 95% and 90%. An SpO2 of 95 reflects a PaO2 of ~80 mm Hg. This is by definition the lower limit of normal oxygenation. The precise oxygen tensions for saturations above 95 are irrelevant; they reflect normal PaO2. An SpO2 of 90 reflects a PaO2 of ~60 mm Hg. By definition, this is hypoxemia, but it is well above the normal intracellular oxygen tension of 40 mm Hg.
More importantly, 90% saturation represents a critical point on the oxygen-hemoglobin dissociation curve (See Figure 1). Further decline leads to a precipitous drop in saturation, thus oxygenation, as hemoglobin loses oxygen rapidly. Saturation that declines to 90% is at the “edge of the cliff” and is a warning to aggressively reestablish adequate ventilation. PaO2 extrapolations no longer require memorization because they are ~30 less than the SpO2 reading. For example, if hemoglobin saturation is 83%, the PaO2 is ~53 mm Hg.
While PaO2 is used to assess oxygenation, PaCO2 is the true measure of ventilation.
Detaljert om betennelser og immunceller etter hard trening, relatert til DOMS.
http://www.ncbi.nlm.nih.gov/pubmed/16385845
Klikk for å få tilgang til article.pdf
Eccentric exercise commonly results in muscle damage. The primary sequence of events leading to exercise-induced muscle damage is believed to involve initial mechanical disruption of sarcomeres, followed by impaired excitation-contraction coupling and calcium signaling, and finally, activation of calcium-sensitive degradation pathways. Muscle damage is characterized by ultrastructural changes to muscle architecture, increased muscleproteins and enzymes in the bloodstream, loss of muscular strength and range of motion and muscle soreness. The inflammatory response to exercise-induced muscle damage is characterized by leukocyte infiltration and production of pro-inflammatory cytokines within damaged muscle tissue, systemic release of leukocytes and cytokines, in addition to alterations in leukocyte receptor expression and functional activity. Current evidence suggests that inflammatory responses to muscle damage are dependent on the type of eccentric exercise, previous eccentric loading (repeated bouts), age and gender. Circulating neutrophil counts and systemic cytokine responses are greater after eccentric exercise using a large muscle mass (e.g. downhill running, eccentric cycling) than after other types of eccentric exercise involving a smaller muscle mass. After an initial bout of eccentric exercise, circulating leukocyte counts and cell surface receptor expression are attenuated. Leukocyte and cytokine responses to eccentric exercise are impaired in elderly individuals, while cellular infiltration into skeletal muscle is greater in human females than males after eccentric exercise. Whether alterations in intracellular calcium homeostasis influence inflammatory responses to muscle damage is uncertain. Furthermore, the effects of antioxidant supplements are variable, and the limited data available indicates that anti-inflammatory drugs largely have no influence on inflammatory responses to eccentric exercise. In this review, we compare local versus systemic inflammatory responses, and discuss some of the possible mechanisms regulating the inflammatory responses to exercise-induced muscle damage in humans.
Denne inneholder alt om DOMS. Nevner 6 foreslåtte årsaker, og at det sannsynligvis er en blanding av flere av dem hver gang: melkesyre, muskelkrampe, vevskade, muskelskade, betennelse og enzymeffluks teorier.
http://www.ncbi.nlm.nih.gov/pubmed/12617692
ftp://192.195.81.82/AiDisk_b1/MCD%20E-BOOKS/Personal%20Interest/WORKOUT/Delayed%20Onset%20Muscle%20Soreness.pdf
Delayed onset muscle soreness (DOMS) is a familiar experience for the elite or novice athlete. Symptoms can range from muscle tenderness to severe debilitating pain. The mechanisms, treatment strategies, and impact on athletic performance remain uncertain, despite the high incidence of DOMS. DOMS is most prevalent at the beginning of the sporting season when athletes are returning to training following a period of reduced activity. DOMS is also common when athletes are first introduced to certain types of activities regardless of the time of year. Eccentric activities induce micro-injury at a greater frequency and severity than other types of muscle actions. The intensity and duration of exercise are also important factors in DOMS onset. Up to six hypothesised theories have been proposed for the mechanism of DOMS, namely: lactic acid, muscle spasm, connective tissue damage,muscle damage, inflammation and the enzyme efflux theories. However, an integration of two or more theories is likely to explain muscle soreness. DOMS can affect athletic performance by causing a reduction in joint range of motion, shock attenuation and peak torque. Alterations in muscle sequencing and recruitment patterns may also occur, causing unaccustomed stress to be placed on muscle ligaments and tendons. These compensatory mechanisms may increase the risk of further injury if a premature return to sport is attempted.A number of treatment strategies have been introduced to help alleviate the severity of DOMS and to restore the maximal function of the muscles as rapidly as possible. Nonsteroidal anti-inflammatory drugs have demonstrated dosage-dependent effects that may also be influenced by the time of administration. Similarly, massage has shown varying results that may be attributed to the time of massage application and the type of massage technique used. Cryotherapy, stretching, homeopathy, ultrasound and electrical current modalities have demonstrated no effect on the alleviation of muscle soreness or other DOMS symptoms. Exercise is the most effective means of alleviating pain during DOMS, however the analgesic effect is also temporary. Athletes who must train on a daily basis should be encouraged to reduce the intensity and duration of exercise for 1-2 days following intense DOMS-inducing exercise. Alternatively, exercises targeting less affected body parts should be encouraged in order to allow the most affected muscle groups to recover. Eccentric exercises or novel activities should be introduced progressively over a period of 1 or 2 weeks at the beginning of, or during, the sporting season in order to reduce the level of physical impairment and/or training disruption. There are still many unanswered questions relating to DOMS, and many potential areas for future research.
Veldig viktig studie som nevner at det ikke finnes glatt muskulatur i kapillærene, så det er arteriolene som avgjør blodsirkulasjonen i kapillærene. His blodsirkulasjonen i en arteriole blir dårlig stopper sirkulasjonen opp i et område av muskelen som serveres av kapillærene.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4000229
The rising incidence of diabetes and the associated metabolic diseases including obesity, cardiovascular disease and hypertension have led to investigation of a number of drugs to treat these diseases. However, lifestyle interventions including diet and exercise remain the first line of defense. The benefits of exercise are typically presented in terms of weight loss, improved body composition and reduced fat mass, but exercise can have many other beneficial effects. Acute effects of exercise include major changes in blood flow through active muscle, an active hyperemia that increases the delivery of oxygen to the working muscle fibers. Longer term exercise training can affect the vasculature, improving endothelial health and possibly basal metabolic rates. Further, insulin sensitivity is improved both acutely after a single bout of exercise and shows chronic effects with exercise training, effectively reducing diabetes risk. Exercise-mediated improvements in endothelial function may also reduce complications associated with both diabetes and other metabolic disease. Thus, while drugs to improve microvascular function in diabetes continue to be investigated, exercise can also provide many similar benefits on endothelial function and should remain the first prescription when treating insulin resistance and diabetes. This review will investigate the effects of exercise on the blood vessel and the potential benefits of exercise on cardiovascular disease and diabetes.
At rest, a low proportion of capillaries are exposed to blood flow at one time, with a rapid increase in the number of perfused capillaries after exercise [31], thus increasing functional capillary density.
Vascular smooth muscle cells are located around the arterioles and some venules, and can constrict to change blood flow patterns, while capillaries do not typically contribute to blood flow changes [30] (Figure 1). Blood flow through capillaries is controlled upstream by small arterioles at rest, and the rapid recruitment of unperfused capillaries by exercise could suggest that nerves are responsible for this action [34]. The sympathetic nervous system is mainly responsible for the vasoconstrictor responses, and as the arterioles and larger vessels are innervated [38] the majority of sympathetic nervous system activity is localized to that area of the vascular tree. Physical exercise can enhance sympathetic nerve activity [39] to maintain arterial pressure, and may be involved in maintaining exercise tolerance, as reviewed by Thomas and Segal [38].
Structural differences between artery, arteriole and capillary. No vascular smooth muscle is located on the capillary; therefore flow through capillaires is modified by pre-capillary arterioles. Cessation of flow through arterioles will prevent flow through a portion of the muscle.
Insulin relies on endothelium-dependent vasodilation to enhance perfusion, thus endothelial dysfunction reduces insulin-mediated increases in muscle perfusion, which can contribute to the metabolic deficit in diabetes. As exercise-mediated changes in perfusion are typically endothelium-independent, exercise is still able to recruit capillaries and thus increase muscle perfusion in obesity and type 2 diabetes, even in the face of endothelial dysfunction. Numerous studies have now shown that while insulin’s vascular effects may be blocked in diabetes, exercise still maintains its ability to increase the distribution of blood flow through muscle [42].
Nitric oxide (NO) is the main vasodilator from the endothelium specifically involved in blood flow and blood distribution, and while reduction in nitric oxide synthesis lowered total blood flow, exercise-mediated capillary recruitment was not affected [46]. In fact, inhibition of NO formation enhances both resting and exercise-mediated muscle oxygen uptake [47]; despite a reduction in total flow, microvascular flow was not affected, suggesting that NO is not involved in the vascular response to exercise.
The distribution of blood through muscle increases the capacity for nutrient exchange. In exercise the primary purpose of functional hyperemiais for oxygen delivery, as the oxygen required by exercising muscle is much higher than resting muscle (reviewed in [37]). Recruitment of capillaries can decrease the velocity of blood flow by increasing the cross-sectional area of the capillary bed and the time available for exchange. Recruitment also increases surface area for exchange and decreases perfusion distances to promote oxygen delivery to tissues with exercise [34] (Figure 2). While in exercise the main metabolite required at the working muscle is oxygen, distribution of other nutrients can also be affected, including glucose, fats, other hormones and cytokines. Muscle metabolism can therefore be altered by perfusion of the tissue [48,49]. While there can be regulated transport of certain larger hormones across the vasculature [50,51], smaller molecules can diffuse across the endothelium easily, possibly making muscle perfusion a more important player in the delivery of glucose and oxygen to the tissue.
Vasodilation affects delivery, and thus metabolism. The rate of transfer across the endothelium is dependent on surface area, permeability of the endothelium, diffusion distance, and concentration difference (Fick’s first law of diffusion). Vasodilation increases surface area in arterioles for exchange, but will also recruit downstream capillaries, which will reduce diffusion distance and increase surface area for exchange. Working muscle increases oxygen utilization, increasing the concentration difference from the blood vessel to the tissue.
Mitochondrial dysfunction has been proposed to be both a cause [72] and a consequence [73] of insulin resistance, and may contribute to endothelial dysfunction [74]. If oxygen delivery is a component of mitochondrial health and biogenesis, it is possible that impaired perfusion may contribute to fiber type switching, where an oxidative fiber, which is typically highly vascularized and contains mitochondria, switches to a glycolytic fiber with less vascularity and mitochondria. As exercise can improve oxidative capacity, increase mitochondria content [75], and also increase muscle perfusion [31,32,34,45,76], the relationship between muscle perfusion, fiber type and mitochondrial function needs to be clarified.
The vascular component of exercise may well be linked to the reduction of diabetic complication such as retinopathy, peripheral neuropathy and nephropathy, as there is a vascular basis to many of these complications. The endothelium has been implicated in diabetic nephropathy [88], and the blood vessels formed in response to reduced perfusion in retinopathy show abnormal structure and function [89].
Spennende studie som nevner at blodsirkulasjonen øker i området som har stølhet. Og den økte blodsirkulasjonen vedvarer i mer enn 48 timer etter treningen. I dette tilfellet i leggen som ble trent. De mener det er pga økt betennelse i muskelen.
There was a significant main effect for time for blood volume (p=0.023) and blood flow (p=0.010), with no significant difference in blood flow velocity (p=0.316). There were significant increases in blood volume (p=0.001) and blood flow (p<0.001) immediately postexercise (9.77 ± 3.19 dB and 3.53 ± 0.86 dB/sec), respectfully in the contralateral limb compared to baseline (6.18 ± 2.05 dB and 2.40 ± 0.69), with no change in blood flow velocity (p=0.487). The effect size for blood volume was 1.34 (0.09, 2.60) and blood flow was 1.41 (0.15, 2.68). The increases in contra lateral blood volume (p=0.002) and blood flow (p=0.003) were maintained at 48 hours (9.41 ± 1.90 dB and 3.51 ± 0.47 dB/sec) compared to baseline, with again no change in blood flow velocity (p=0.411). The effect size for blood volume was 1.62 (0.32, 2.92) and blood flow was 1.86 (0.51, 3.22). There were no changes in blood volume (p=0.814), blood flow (p=0.962), or blood flow velocity (p=0.493) between post-exercise and 48 hours for the contra lateral limb.
Following eccentric exercise to a single limb, the contralateral limb resulted in increased blood volume and blood flow immediately after exercise and at 48 hours post exercise. From previous research in our lab [12] immediately after eccentric exercise, blood volume and blood flow increased in the exercise leg by 42% and 80%, respectfully. From this study, the contra lateral leg increased 17% and 35% for blood volume and blood flow, respectfully. This finding supports earlier work by Seals [7] and Taylor et al. [8] that identified vasodilatation of the contra lateral limb after exercise initiation. Blood flow velocity did not change in the contra lateral limb after exercise and at 48 hours. Since this limb was not exercised, recruitment of capillaries is not necessary, as would be in exercised muscle [14].
Eccentric exercise increased microvascular perfusion immediately after exercise in the contralateral limb, which had not been examined before. The increased perfusion was maintained over 48 hours, so the prolonged increased in perfusion of the contralateral limb may have been due to an inflammatory response or the extra demands placed on the contralateral limb for support during walking.
Denne studien beskriver hvordan systemisk betennelse påvirker pustefunksjonen og gjør at det blir vanskeligere å endre pustemønser, f.eks. å gjøre pusteøvelser, eller å tilpasse pusten til aktivitetsnivå. Spesielt den kjemiske og motoriske delen av pustefysiologien blir dårligere. Noe som viser seg i laver CO2 sensitivitet (kjemisk) og svakere pustemuskler (Motorisk).
Nevner spesielt at det er mikroglia celler i CNS som påvirkes av betennelse, og som kan oppretthodle betennelse siden de sender ut cytokiner, m.m. Astrosytter kan også bidra mye siden de aktiverer NFkB. Den gode nyheten her er at økt CO2 nedregulerer NFkB. TLR-4 (Toll-like receptor) aktiveres av patogener og problemer i cellene, og aktiverer NFkB, og nedreguleres av økt CO2.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3172820/
Many lung and central nervous system disorders require robust and appropriate physiological responses to assure adequate breathing. Factors undermining the efficacy of ventilatory control will diminish the ability to compensate for pathology, threatening life itself. Although most of these same disorders are associated with systemic and/or neuroinflammation, and inflammation affects neural function, we are only beginning to understand interactions between inflammation and any aspect of ventilatory control (e.g. sensory receptors, rhythm generation, chemoreflexes, plasticity). Here we review available evidence, and present limited new data suggesting that systemic (or neural) inflammation impairs two key elements of ventilatory control: chemoreflexes and respiratory motor (vs. sensory) plasticity. Achieving an understanding of mechanisms whereby inflammation undermines ventilatory control is fundamental since inflammation may diminish the capacity for natural, compensatory responses during pathological states, and the ability to harness respiratory plasticity as a therapeutic strategy in the treatment of devastating breathing disorders, such as during cervical spinal injury or motor neuron disease.
Most lung and CNS disorders are associated with systemic and/or neural inflammation, including chronic lung diseases (Stockley, 2009), traumatic, ischemic and degenerative neural disorders (Teeling and Perry, 2009) and obstructive sleep apnea.
Systemic inflammation affects sensory receptors that modulate breathing, but can also trigger inflammatory responses in the central nervous system (CNS) through complex mechanisms. The primary CNS cells affected during systemic inflammation are microglia, the resident immune cells of the CNS, and astrocytes (Lehnardt, 2010).
Even when in their “resting state,” microglia are highly active, surveying their environment (Raivich, 2005,Parkhurst and Gan, 2010). When confronted with pathological conditions, such as neuronal injury/degeneration or bacterial/viral/fungal infection, they become “activated,” shifting from a stellate, ramified phenotype to an amoeboid shape (Kreutzberg, 1996). Activated microglia can be phagocytic, or they can release toxic and protective factors, including cytokines, prostaglandins, nitric oxide or neurotrophic factors (e.g. BDNF) (Kreutzberg, 1996, Graeber, 2010). Despite the importance of microglia in immune function, they are diffuse in the CNS (~70-90% of CNS cells are glia; microglia are ~5-10% of those cells).
Astrocytes, on the other hand, contribute to the overall inflammatory response since they release cytokines, triggering nuclear factor-kappa B (NFκB) signaling elsewhere in the CNS. Further, they express many TLRs, including TLR-4, capable of eliciting an inflammatory response (Li and Stark, 2002, Farina et al., 2007,Johann et al., 2008). Given their relative abundance, astrocytes may play a key role in CNS inflammatory responses.
TLR-4 receptors are cytokine family receptors that activate transcription factors, such as NFκB (Lu et al., 2008). NFκB regulates the expression of many inflammatory genes, including: IL-1β, -6 and -18, TNFα, cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) (Ricciardolo et al., 2004, Nam, 2006). Endogenous molecules known to activate TLR-4 receptors include (but are not limited to) heat shock proteins (specifically HSP60, Ohashi et al., 2000, Lehnardt et al., 2008), fibrinogen, surfactant protein-A, fibronectin extra domain A, heparin sulfate, soluble hyaluronan, β-defensin 2 and HMGB1 (Chen et al., 2007).
The role of inflammation (and specifically microglia) in chronic pain has been studied extensively (reviewed in Woolf and Salter, 2000, Trang et al., 2006, Mika, 2008, Abbadie et al., 2009, Baumbauer et al., 2009). A remarkable story has emerged, demonstrating the interplay between neurons, microglia, inflammation and plasticity in this spinal sensory system. In short, inflammation induces both peripheral and central sensitization, leading to allodynia (hypersensitivity to otherwise non-painful stimuli) and hyperalgesia (exaggerated or prolonged responses to a noxious stimulus) (Mika, 2008).
An important aspect of ventilatory control susceptible to inflammatory modulation is the chemoreflex control of breathing. Chemoreflexes are critical for maintaining homeostasis of arterial blood gases viaclassical negative feedback (Mitchell et al., 2009), or acting as “teachers” that induce plasticity in the respiratory control system (Mitchell and Johnson, 2003). Major chemoreflexes include the hypoxic (Powell et al., 1998) and hypercapnic ventilatory responses (Nattie, 2001), arising predominantly from the peripheral arterial and central chemoreceptors (Lahiri and Forster, 2003).
To date, no studies have reported the impact of systemic inflammation on hypercapnic responses. However, increased CO2 suppresses NFκB activation, possibly suppressing inflammatory gene expression (Taylor and Cummins, 2011). In fact, hypercapnia has been used to treat ischemia/reperfusion injury to decrease inflammation and reduce lung tissue damage (Laffey et al., 2000, O’Croinin et al., 2005, Curley et al., 2010, Li et al., 2010).
Further work concerning the influence of systemic inflammation on hypercapnic ventilatory responses is warranted, particularly since impaired CO2 chemoreflexes would allow greater hypercapnia and minimize the ongoing inflammation; in this sense, impaired hypercapnic ventilatory responses during inflammation may (in part) be adaptive.
Dette er en ekstremt viktig studie på hvorfor melkesyre er så misforstått og hva det er som egentlig skaper syreoverskudd i musklene.
Det viser seg at melkesyre faktisk er en beskyttende faktor og reduserer syreoverskudd ved at 2 H+ ioner brukes i prosessen til å skape ett melkesyremolekyl (som kan avgi 1 H+).
Melkesyreterskel er fortsatt en indikasjon på når syreoverskuddet tar overhånd i musklene, men problemene man kjenner har svært lite med melkesyre å gjøre.
Metabolsk acidose oppstår når ATP behovet blir større enn mitokondrienes hastighet i ATP-produksjonen.
Mitokondriene ikke får skapt nok ATP (energi) raskt nok, og produseres det utenfor mitokondriene i en prosess som produserer mye syre (H+ ioner). Utenfor mitokondriene er det mye dårligere forsvar mot syre (H+) og det blir lettere syreoverskudd.
Melkesyre (og CO2) er to faktorer som faktisk beskytter mot syreoverskudd.
http://ajpregu.physiology.org/content/287/3/R502
The development of acidosis during intense exercise has traditionally been explained by the increased production of lactic acid, causing the release of a proton and the formation of the acid salt sodium lactate. On the basis of this explanation, if the rate of lactate production is high enough, the cellular proton buffering capacity can be exceeded, resulting in a decrease in cellular pH. These biochemical events have been termed lactic acidosis. The lactic acidosis of exercise has been a classic explanation of the biochemistry of acidosis for more than 80 years. This belief has led to the interpretation that lactate production causes acidosis and, in turn, that increased lactate production is one of the several causes of muscle fatigue during intense exercise. This review presents clear evidence that there is no biochemical support for lactate production causing acidosis. Lactate production retards, not causes, acidosis. Similarly, there is a wealth of research evidence to show that acidosis is caused by reactions other than lactate production. Every time ATP is broken down to ADP and Pi, a proton is released. When the ATP demand of muscle contraction is met by mitochondrial respiration, there is no proton accumulation in the cell, as protons are used by the mitochondria for oxidative phosphorylation and to maintain the proton gradient in the intermembranous space. It is only when the exercise intensity increases beyond steady state that there is a need for greater reliance on ATP regeneration from glycolysis and the phosphagen system. The ATP that is supplied from these nonmitochondrial sources and is eventually used to fuel muscle contraction increases proton release and causes the acidosis of intense exercise. Lactate production increases under these cellular conditions to prevent pyruvate accumulation and supply the NAD+ needed for phase 2 of glycolysis. Thus increased lactate production coincides with cellular acidosis and remains a good indirect marker for cell metabolic conditions that induce metabolic acidosis. If muscle did not produce lactate, acidosis and muscle fatigue would occur more quickly and exercise performance would be severely impaired.
Although metabolic acidosis is caused by cytosolic (nonmitochondrial) catabolism, an understanding of why and when metabolic acidosis occurs in contracting skeletal muscle is partly explained by knowing how and why mitochondrial function can be rate limiting to ATP regeneration.
The proton transport systems between the cytosol and mitochondria are revealing of the power of mitochondrial respiration in contributing to the control over the balance of protons within the cell during conditions of muscle contraction that rely on mitochondrial respiration for ATP turnover.
Fig. 12.
A summary of the main reactions of mitochondrial respiration that support ATP regeneration. Note that each of cytosolic ADP, Pi, electrons (e−), and protons (H+) can enter the mitochondria (whether directly or indirectly) and function as substrates for oxidative phosphorylation.
Figure 14, A and B, present two scenarios of metabolism pertinent to the study of acidosis. Figure 14A depicts the movement of carbon substrate, electrons, protons, and phosphate molecules within and between the cytosol and mitochondria during moderate intensity steady-state exercise where the rate of glycolysis and subsequent pyruvate entry into the mitochondria for complete oxidation and mitochondrial ATP regeneration meet the rate of cytosolic ATP demand. Conversely, Fig. 14Bpertains to non-steady-state exercise as is typified by intense exercise to volitional fatigue within a time frame of 2–3 min. In each figure example, the magnitude of the arrows is proportionate to substrate flux through that reaction or pathway.
Fig. 14.
Two diagrams representing energy metabolism in skeletal muscle during two different exercise intensities. A: steady state at ∼60% V̇O2 max. Note that macronutrients are a mix of blood glucose, muscle glycogen, blood free fatty acids, and intramuscular lipid. Blood free fatty acids and intramuscular lipolysis eventually yield the activated fatty acid molecules (FA-CoA). Pyruvate, NADH, and protons produced from substrate flux through glycolysis are predominantly consumed by the mitochondria as substrates for mitochondrial respiration. The same is true for the products of ATP hydrolysis (ADP, Pi, H+). Such a metabolic scenario can be said to be pH neutral to the muscle cells. B: short-term intense exercise at ∼110% V̇O2 max, causing volitional fatigue in ∼2–3 min. Size of the arrows approximate relative dependence/involvement of that reaction and the predominant fate of the products. Note that Pi is also a substrate of glycogenolysis. In this scenario, cellular ATP hydrolysis is occurring at a rate that cannot be 100% supported by mitochondrial respiration. Thus there is increased reliance on using cellular ADP for ATP regeneration from glycolysis and creatine phosphate. For every ADP that is used in glycolysis and the creatine kinase reaction under these cellular conditions, a Pi and proton is released into the cytosol. However, the magnitude of proton release is greater than for Pidue to the need to recycle Pi as a substrate in glycolysis and glycogenolysis. As explained in the text, the final accumulation of protons is a balance between the reactions that consume and release protons, cell buffering, and proton transport out of the cell. This diagram also clearly shows that the biochemical cause of proton accumulation is not lactate production but ATP hydrolysis.
The additional underlying message of Fig. 14 is that the cellular mitochondrial capacity is pivotal in understanding metabolic acidosis. The mitochondrial capacity for acquiring cytosolic protons and electrons retards a dependence on glycolysis and the phosphagen system for ATP regeneration, essentially functioning as a depository for protons for use in oxidative phosphorylation. Metabolic acidosis occurs when the rate of ATP hydrolysis, and therefore the rate of ATP demand, exceeds the rate at which ATP is produced in the mitochondria.
The intracellular buffering system, which includes amino acids, proteins, Pi, HCO3−, creatine phosphate (CrP) hydrolysis, and lactate production, binds or consumes H+ to protect the cell against intracellular proton accumulation. Protons are also removed from the cytosol via mitochondrial transport, sarcolemmal transport (lactate−/H+ symporters, Na+/H+exchangers), and a bicarbonate-dependent exchanger (HCO3−/Cl−) (Fig. 13). Such membrane exchange systems are crucial for the influence of the strong ion difference approach at understanding acid-base regulation during metabolic acidosis (5, 26). It is important to note that lactate production acts as both a buffering system, by consuming H+, and a proton remover, by transporting H+ across the sarcolemma, to protect the cell against metabolic acidosis.
Fig. 16.
Comparison between the theoretical proton release from lactate production to the known skeletal muscle buffer capacity (structural and metabolic). For example, if lactate production released protons, then the magnitude of the 2 columns of data should equal each other. Data for muscle lactate, CrP and Pi from Spriet et al. (49, 50). Data for muscle buffer capacity (by titration) from Sahlin (38) at 42 slykes for a muscle pH decrease from 7.0 to 6.4.
Fig. 17.
Balance between intramuscular proton release and consumption based on fundamental biochemistry, as explained in the text. Data for nonmitochondrial ATP turnover (ATP-NM) from Bangsbo et al. (1) at 370 mmol/kg dry wt. Data for glycolysis from Spriet et al. (50) at 73.8 mmol glucosyl units/kg dry wt. Data for muscle lactate, CrP, Pi, and buffer capacity as for Fig. 16.
The data from Figs. 16 and 17 are very important as they show that nonmitochondrial ATP turnover is not just a theoretical explanation of metabolic acidosis, as is argued by many due to Eq. 5. The fact is that research clearly supports the stoichiometry of the nonmitochondrial ATP turnover cause of metabolic acidosis. In so doing, research also clearly discredits the interpretation of acidosis as being caused by lactate production.
The most important reason to discard the lactic acidosis concept is that it is invalid. It has no biochemical justification and, to no surprise, no research support. We have been criticized for our stance on the need to change how to teach and interpret metabolic acidosis based on Eq. 5(glucose → 2 lactate + 2 H+). However, this is a summary equation that does not represent cause and effect, as previously described and illustrated in Fig. 10. As such, the concept of a lactic acidosis remains evidence of 1920s academic and scientific inertia that, out of simple convenience and apathy, still remains today. We would hope that the academics and professionals from the basic and applied fields that continue to accept the lactic acidosis construct immediately change the way they teach and interpret this topic.
Svært interessant og bra skrevet blogg innlegg.
http://thesportsphysio.wordpress.com/2014/06/16/there-is-no-skill-in-manual-therapy-2/
For example, I learnt you can’t break down scar tissue, ‘release’ a muscle or a fascial adhesion (Chaudhry 2008, Chaudhry 2007, Schleip 2003, Threlkeld 1992)
I learnt that by stretching a muscle in a certain fashion, in a certain way, for a certain amount of time doesnt effect it’s structure (Solomonow 2007, Weppler 2010, Katalinic 2011)
I learnt that you don’t need to mobilise or manipulate a joint in a specific direction, based on a specific assessment of pain and joint feel (Chiradejnant 2003, Aquino 2009, Schomacher 2009, Nyberg 2013)
I learnt that palpation of muscles, joints, trigger points are all unreliable and can lead to questionable diagnosis that often direct treatment down wrong and ineffective pathways, I have done a blog on this particular topic recently with all the supporting evidence here.
I leant that when all the methods and techniques of manual therapy are examined through the process of systematic reviews and meta analysis most of the research is poor and even the good research shows that it doesn’t do much (Menke 2014,Kumar 2014, Artus 2010, Kent 2005)
Verkstedet Bodywork & Breathing System 