Distinct mechanisms underlie adaptation of proximal tubule Na+/H+ exchanger isoform 3 in response to chronic metabolic and respiratory acidosis

The Na+/H+ exchanger isoform 3 (NHE3) is essential for HCO3- reabsorption in renal proximal tubules. The expression and function of NHE3 must adapt to acid-base conditions. The goal of this study was to elucidate the mechanisms responsible for higher proton secretion in proximal tubules during acidosis and to evaluate whether there are differences between metabolic and respiratory acidosis with regard to NHE3 modulation and, if so, to identify the relevant parameters that may trigger these distinct adaptive responses. We achieved metabolic acidosis by lowering HCO3- concentration in the cell culture medium and respiratory acidosis by increasing CO2 tension in the incubator chamber. We found that cell-surface NHE3 expression was increased in response to both forms of acidosis. Mild (pH 7.21 +/- 0.02) and severe (6.95 +/- 0.07) metabolic acidosis increased mRNA levels, at least in part due to up-regulation of transcription, whilst mild (7.11 +/- 0.03) and severe (6.86 +/- 0.01) respiratory acidosis did not up-regulate NHE3 expression. Analyses of the Nhe3 promoter region suggested that the regulatory elements sensitive to metabolic acidosis are located between -466 and -153 bp, where two consensus binding sites for SP1, a transcription factor up-regulated in metabolic acidosis, were localised. We conclude that metabolic acidosis induces Nhe3 promoter activation, which results in higher mRNA and total protein level. At the plasma membrane surface, NHE3 expression was increased in metabolic and respiratory acidosis alike, suggesting that low pH is responsible for NHE3 displacement to the cell surface.

Blood-respiratory and acid-base changes during extended diving in the bimodally respiring freshwater turtle Rheodytes leukops

Changes in blood-gas, acid-base, and plasma-ion status were investigated in the bimodally respiring turtle, Rheodytes leukops, during prolonged dives of up to 12 h. Given that R. leukops routinely submerges for several hours, the objective of this study was to determine whether voluntarily diving turtles remain aerobic and simultaneously avoid hypercapnic conditions over increasing dive lengths. Blood PO2, PCO2, and pH, as well as plasma concentrations of lactate, glucose, Na+, K+, Cl-, total Ca, and total Mg were determined in venous blood collected from the occipital sinus. Blood PO2 declined significantly with dive length; however, oxy-haemoglobin saturation remained greater than 30% for all R. leukops sampled. No changes were observed in blood PCO2, pH, [HCO3-], or plasma glucose, with increasing dive length. Despite repeated dives lasting more than 2 h, plasma lactate remained less than 3 mmol l(-1) for all R. leukops sampled, indicating the absence of anaerobiosis. Compensatory acid-base adjustments associated with anaerobiosis (e.g. declining [Cl-], increasing total [Ca] and [Mg]) were likewise absent, with plasma-ion concentrations remaining stable with increasing dive length. Results indicate that R. leukops utilises aquatic respiration to remain aerobic during prolonged dives, thus effectively avoiding the development of a metabolic and respiratory acidosis.

The hyperthermic patient

Concepts used in this chapter include: Thermoregulation:- Thermoregulation refers to the body’s sophisticated, multi-system regulation of core body temperature. This hierarchical system extends from highly thermo-sensitive neurons in the preoptic region of the brain proximate to the rostral hypothalamus, down to the brain stem and spinal cord. Coupled with receptors in the skin and spine, both central and peripheral information on body temperature is integrated to inform and activate the homeostatic mechanisms which maintain our core temperature at 37oC1. Hyperthermia:- An imbalance between the metabolic and external heat accumulated in the body and the loss of heat from the body2. Exertional heat stroke:- A disorder of excessive heat production coupled with insufficient heat dissipation which occurs in un-acclimated individuals who are engaging in over-exertion in hot and humid conditions. This phenomenon includes central nervous system dysfunction and critical dysfunction to all organ systems including renal, cardiovascular, musculoskeletal and hepatic functions. Non-exertional heat stroke:- In contrast to exertional heatstroke as a consequence of high heat production during strenuous exercise, non-exertional heatstroke results from prolonged exposure to high ambient temperature. The elderly, those with chronic health conditions and children are particularly susceptible.3 Rhabdomylosis:- An acute, sometimes fatal disease characterised by destruction of skeletal muscle. In exertional heat stroke, rhabdomylosis occurs in the context of strenuous exercise when mechanical and/or metabolic stress damages the skeletal muscle, causing elevated serum creatine kinease. Associated with this is the potential development of hyperkalemia, myoglobinuria and renal failure. Malignant hyperthermia:- Malignant hyperthermia is “an inherited subclinical myopathy characterised by a hypermetabolic reaction during anaesthesia. The reaction is related to skeletal muscle calcium dysregulation triggered by volatile inhaled anaesthetics and/or succinylcholine.”4 Presentation includes skeletal muscle rigidity, mixed metabolic and respiratory acidosis, tachycardia, hyperpyrexia, rhabdomylosis, hyperkalaemia, elevated serum creatine kinease, multi-organ failure, disseminated intravascular coagulation and death.5

Environmentally induced physiological responses that determine fish survival and distribution: a review

Limitation to an aqueous habitat is the most fundamental physiological constraint imposed upon fish, phrases such as 'like a fish of water', convey our acceptance of the general unsuitability of fish for terrestrial existence. The constraints that restrict fish to an aquatic habitat relate to respiration, acid-base regulation, nitrogenous excretion, water balance and ionic regulation. A fish not adapted for an amphibious lifestyle when removed from water, becomes hypoxic and hypercapnic and soon succumbs to respiratory acidosis because the problem of excretion of H super(+) and C0 sub(2) are more immediate than lack of oxygen. This happen because fish gills collapse in air, while the ventilator arrangements that moves an incompressible medium (water) oven them become ineffective

The physiological effects of multiple forced submergences in loggerhead sea turtles (Caretta caretta)

Sea turtles are subjected to involuntary submergence and potential mortality due to incidental capture by the commercial shrimp fishing industry. Despite implementation of turtle excluder devices (TEDs) to reduce at-sea mortality, dead stranded turtles continue to be found in near-record numbers along the coasts of the western Atlantic Ocean and northern Gulf of Mexico. Although this mortality may be due to an increase in the number of turtles available to strand, one alternative explanation is that sea turtles are repetitively submerged (as one fishing vessel follows the path of another) in legal TEDs. In the present study, laboratory and field investigations were undertaken to examine the physiological effects of multiple submergence of loggerhead sea turtles (Caretta caretta). Turtles in the laboratory study were confined during the submersion episodes, whereas under field conditions, turtles were released directly into TED-equipped commercial fishing nets. Under laboratory and field conditions, pre- and postsubmergence blood samples were collected from turtles submerged three times at 7.5 min per episode with an in-water rest interval of 10, 42, or 180 min between submergences. Analyses of pre- and postsubmergence blood samples revealed that the initial submergence produced a severe and pronounced metabolic and respiratory acidosis in all turtles. Successive submergences produced significant changes in blood pH, Pco2, and lactate, although the magnitude of the acid-base imbalance was substantially reduced as the number of submergences increased. In addition, increasing the interval between successive submergences permitted greater recovery of blood homeostasis. No turtles died during these studies. Taken together, these data suggest that repetitive sub-mergence of sea turtles in TEDs would not significantly affect their survival potential provided that the animal has an adequate rest interval at the surface between successive submergences.

Living in warmer, more acidic oceans retards physiological recovery from tidal emersion in the velvet swimming crab, Necora puber

The distribution patterns of many species in the intertidal zone are partly determined by their ability to survive and recover from tidal emersion. During emersion, most crustaceans experience gill collapse, impairing gas exchange. Such collapse generates a state of hypoxemia and a hypercapnia-induced respiratory acidosis, leading to hyperlactaemia and metabolic acidosis. However, how such physiological responses to emersion are modified by prior exposure to elevated CO2 and temperature combinations, indicative of future climate change scenarios, is not known. We therefore investigated key physiological responses of velvet swimming crabs, Necora puber, kept for 14 days at one of four pCO(2)/temperature treatments (400 mu atm/10 degrees C, 1000 mu atm/10 degrees C, 400 mu atm/15 degrees C or 1000 mu atm/15 degrees C) to experimental emersion and recovery. Pre-exposure to elevated pCO(2) and temperature increased pre-emersion bicarbonate ion concentrations [HCO3-], increasing resistance to short periods of emersion (90 min). However, there was still a significant acidosis following 180 min emersion in all treatments. The recovery of extracellular acid-base via the removal of extracellular pCO(2) and lactate after emersion was significantly retarded by exposure to both elevated temperature and pCO(2). If elevated environmental pCO(2) and temperature lead to slower recovery after emersion, then some predominantly subtidal species that also inhabit the low to mid shore, such as N. puber, may have a reduced physiological capacity to retain their presence in the low intertidal zone, ultimately affecting their bathymetric range of distribution, as well as the structure and diversity of intertidal assemblages.

Efectos de la ventilación mecánica con heliox en niños y adolescentes con patología bronquial obstructiva

Evaluar si el Heliox reduce la resistencia en la vía aérea en niños y adolescentes con patología bronquial obstructiva que requieren ventilación mecánica. Materiales y Métodos: Estudio prospectivo observacional descriptivo en niños y adolescentes con patología bronquial obstructiva y ventilación mecánica con Fi02 ≤ 0,5. Medición de variables: resistencia, presión pico, presión media de la vía aérea, presión meseta, volumen corriente, autoPEEP, distensibilidad, PetCO2, ventilación de espacio muerto antes de inicio de heliox y a los 30 minutos, 2, 4, 6, 12, 18 y 24 horas y diariamente hasta suspenderlo por extubación o FiO2 > 0,5. Resultados: Resultados parciales, incluyó 9 pacientes encontrando descenso significativo de resistencia espiratoria a los 30 minutos (51,2 vs 32,3; p=0,0008 ), 2 horas ( 51,2 vs 33,4; p=0,0019) y 4 horas (51,2 vs 30,7; p=0,0012) así como de la resistencia inspiratoria a la hora 2 (48,6 vs 36,2; p = 0,013) y hora 4 (48,6 vs 30 ; p=0,004). Se observó tendencia al descenso de la PetCO2 que no fue significativa (52,3 vs 34,3: p=0,06). No se evidenció cambios en las variables; autoPEEP, presión pico, presión media de la vía aérea, distensibilidad, ventilación de espacio muerto, presión meseta y volumen corriente antes y después del inicio del Heliox. Conclusión: La ventilación mecánica con Heliox en niños con patología bronquial obstructiva parece ser que reduce de manera significativa la resistencia de la vía aérea, con tendencia al descenso de la PetC02. Se necesitan estudios prospectivos al menos observacionales analíticos que corroboren estos hallazgos.

Cardiopulmonary and acid-base effects of desflurane and sevoflurane in spontaneously breathing cats

The cardiopulmonary effects of desflurane and sevoflurane anesthesia were compared in cats breathing spontaneously. Heart (HR) and respiratory (RR) rates; systolic (SAP), diastolic (DAP) and mean arterial (MAP) pressures; partial pressure of end tidal carbon dioxide (PETCO(2)), arterial blood pH (pH), arterial partial pressure of oxygen (PaO(2)) and carbon dioxide (PaCO(2)); base deficit (BD), arterial oxygen saturation (SaO(2)) and bicarbonate ion concentration (HCO(3)) were measured. Anesthesia was induced with propofol (8 +/- 2.3 mg/kg IV) and maintained with desflurane (GD) or sevoflurane (GS), both at 1.3 MAC. Data were analyzed by analysis of variance (ANOVA), followed by the Tukey test (P < 0.05). Both anesthetics showed similar effects. HR and RR decreased when compared to the basal values, but remained constant during inhalant anesthesia and PETCO(2) increased with time. Both anesthetics caused acidemia and hypercapnia, but BD stayed within normal limits. Therefore, despite reducing HR and SAP (GD) when compared to the basal values, desflurane and sevoflurane provide good stability of the cardiovascular parameters during a short period of inhalant anesthesia (T20-T60). However, both volatile anesthetics cause acute respiratory acidosis in cats breathing spontaneously. (c) 2004 ESFM and AAFP. Published by Elsevier Ltd. All rights reserved.

Avaliação hemodinâmica e metabólica da cetamina e cetamina S(+) após a reposição volêmica com hidroxietilamido 130/0,4 e solução salina hipertônica 7,5%

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Influência da temperatura corporal de cascavéis (Crotalus durissus) submetidas à anestesia com cetamina

O estudo objetivou verificar a influência da temperatura corporal nos parâmetros fisiológicos e nos períodos de indução e recuperação anestésicos de cascavéis (Crotalus durissus) anestesiadas com cetamina. Os animais foram previamente submetidos à hipotermia (HIPO) (<22°C) e normotermia (30°C) (NORMO) e anestesiados com 80mg/kg IM de cetamina. Foram avaliados os períodos de latência e recuperação da anestesia por meio do tônus de cabeça, tônus muscular e reflexo de endireitamento. Mensurou-se a frequência cardíaca (FC), tempo de apnéia e temperatura corporal em 0 min e 5, 10, 15, 30, 60, 90, 120 min e análise dos gases sanguíneos em 0 min, 30 e 60 min. Não houve diferença em relação ao período de latência entre os grupos. A recuperação dos animais em HIPO foi mais prolongada (5,5 horas) que em NORMO (3,5 horas). Obteve-se FC no grupo NORMO superior que no grupo HIPO. O tempo de apnéia manteve o mesmo padrão em ambos os grupos. em relação ao basal, tanto em HIPO quanto em NORMO o tempo de apnéia diminuiu acentuadamente entre 5 e 30 min. Observou-se acidose respiratória no grupo NORMO apenas em 0 min. O SvO2 elevou-se significativamente após 30 min, o mesmo ocorrendo com a PvO2. A PvCO2 diminuiu em ambos os grupos após 30 min. Evidenciou-se que a temperatura corporal influencia intrinsecamente o período de recuperação de cascavéis anestesiadas com cetamina.

Anestesia intravenosa total utilizando propofol ou propofol/cetamina em cadelas submetidas à ovariossalpingohisterectomia

Objetivou-se avaliar os efeitos cardiorrespiratório e analgésico da infusão contínua com propofol e propofol/cetamina em cadelas pré-medicadas com atropina e xilazina, submetidas a ovariossalpingohisterectomia (OSH). em seis cadelas (GP) a indução anestésica foi realizada com propofol (5mg kg-1 iv), seguido da manutenção anestésica com o mesmo fármaco em infusão contínua intravenosa na taxa inicial de 0,4mg kg-1.min-1. Outras seis cadelas (GPC) receberam a associação de propofol (3,5mg kg-1 iv) e cetamina (1mg kg-1 iv) como indução anestésica. Depois, foi feita manutenção anestésica em infusão contínua intravenosa inicial com 0,28mg kg-1.min-1 e 0,06mg kg-1.min-1 de propofol e cetamina, respectivamente. Os seguintes parâmetros foram mensurados durante a anestesia a cada 10 minutos: freqüências cardíaca (FC) e respiratória (f), pressão arterial sistólica, média e diastólica (PA), concentração final expirada de CO2 (EtCO2), volume minuto (VM), pressão parcial de gás carbônico (PaCO2), pressão parcial de oxigênio (PaO2), saturação de oxigênio na hemoglobina (SatO2), pH, bicarbonato, glicemia e temperatura retal (T). Observou-se redução da pressão arterial média entre 20 e 40 minutos de anestesia no GP. Ocorreu redução da temperatura, hipercapnia e acidose respiratória em ambos os grupos durante a anestesia. A PaO2, o bicarbonato e a glicose aumentaram de forma significativa apenas no GPC durante a anestesia. Houve necessidade de aumentar em 50 e 20% a taxa de infusão de propofol no GP e GPC respectivamente para anestesia cirúrgica satisfatória. Dessa forma, ambos os protocolos mostraram-se seguros e suficientes do ponto de vista de anestesia cirúrgica para realização da OSH em cadelas, desde que a ventilação assistida ou controlada seja instituída quando necessária e a velocidade de infusão do propofol seja 0,6 e 0,34mg kg-1.min-1 nos grupos GP e GPC, respectivamente.

Effects of chronic acetazolamide administration on gas exchange and acid-base control in pulmonary circulation in exercising horses

P>Reasons for performing study:Carbonic anhydrase (CA) catalyses the hydration/dehydration reaction of CO(2) and increases the rate of Cl- and HCO(3)- exchange between the erythrocytes and plasma. Therefore, chronic inhibition of CA has a potential to attenuate CO(2) output and induce greater metabolic and respiratory acidosis in exercising horses.Objectives:To determine the effects of Carbonic anhydrase inhibition on CO(2) output and ionic exchange between erythrocytes and plasma and their influence on acid-base balance in the pulmonary circulation (across the lung) in exercising horses with and without CA inhibition.Methods:Six horses were exercised to exhaustion on a treadmill without (Con) and with CA inhibition (AczTr). CA inhibition was achieved with administration of acetazolamide (10 mg/kg bwt t.i.d. for 3 days and 30 mg/kg bwt before exercise). Arterial, mixed venous blood and CO(2) output were sampled at rest and during exercise. An integrated physicochemical systems approach was used to describe acid base changes.Results:AczTr decreased the duration of exercise by 45% (P < 0.0001). During the transition from rest to exercise CO(2) output was lower in AczTr (P < 0.0001). Arterial PCO(2) (P < 0.0001; mean +/- s.e. 71 +/- 2 mmHg AczTr, 46 +/- 2 mmHg Con) was higher, whereas hydrogen ion (P = 0.01; 12.8 +/- 0.6 nEq/l AczTr, 15.5 +/- 0.6 nEq/l Con) and bicarbonate (P = 0.007; 5.5 +/- 0.7 mEq/l AczTr, 10.1 +/- 1.3 mEq/l Con) differences across the lung were lower in AczTr compared to Con. No difference was observed in weak electrolytes across the lung. Strong ion difference across the lung was lower in AczTr (P = 0.0003; 4.9 +/- 0.8 mEq AczTr, 7.5 +/- 1.2 mEq Con), which was affected by strong ion changes across the lung with exception of lactate.Conclusions:CO(2) and chloride changes in erythrocytes across the lung seem to be the major contributors to acid-base and ions balance in pulmonary circulation in exercising horses.

Parâmetros hemogasométricos e equilíbrio ácido-básico de cabritos nascidos de partos normais

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Efeitos do modo ventilatório sobre variáveis hemogasométricas em equinos submetidos à mudança de decúbito durante a anestesia geral inalatória com halotano

Compararam-se os efeitos da ventilação espontânea (V E) e controlada (V C) em equinos submetidos à mudança de decúbito durante anestesia. Dezesseis animais foram equitativamente divididos em dois grupos: V E e V C. Os procedimentos cirúrgicos foram iniciados com os animais em decúbito lateral esquerdo (DLE) e, após 75 minutos, os animais foram reposicionados em decúbito lateral direito (DLD). Análises hemogasométricas do sangue arterial foram realizadas após 30 e 75 minutos com os animais posicionados em cada decúbito (M1 e M2 no DLE e M3 e M4 no DLD, respectivamente). Durante a V E, observaram-se hipercapnia (PaCO2 >45mmHg), acidose respiratória (pH <7,35), redução significativa da oxigenação sanguínea após 75min da mudança de decúbito (M4: 205,8±124,7mmHg) em relação aos valores de PaO2 observados antes da mudança de posicionamento (M1: 271,8±84,8mmHg). A Vc foi associada a valores de PaCO2 e pH mais próximos da normalidade bem como resultou em valores de PaO2 significativamente maiores (52 a 96% de elevação nos valores médios) que a V E. Conclui-se que a mudança de decúbito, em equinos anestesiados com halotano e mantidos sob V E, resulta em hipercapnia, acidose respiratória e diminuição dos valores de PaO2. A instituição de V C, desde o início da anestesia, previne a acidose respiratória, além de resultar em valores de PaO2 mais próximos do ideal para animais respirando O2 a 100%.

Midazolam and ketamine induction before halothane anaesthesia in ponies: cardiorespiratory, endocrine and metabolic changes

Six Welsh gelding ponies were premedicated with 0.03 mg/kg of acepromazine intravenously (i.v.) prior to induction of anaesthesia with midazolam at 0.2 mg/kg and ketamine at 2 mg/kg i.v.. Anaesthesia was maintained for 2 h using 1.2% halothane concentration in oxygen. Heart rate, electrocardiograph (EGG), arterial blood pressure, respiratory rate, blood gases, temperature, haematocrit, plasma arginine vasopressin (AVP), dynorphin, beta-endorphin, adrenocorticotropic hormone (ACTH), cortisol, dopamine, noradrenaline, adrenaline, glucose and lactate concentrations were measured before and after premedication, immediately after induction, every 20 min during anaesthesia, and at 20 and 120 min after disconnection. Induction was rapid, excitement-free and good muscle relaxation was observed. There were no changes in heart and respiratory rates, Decrease in temperature, hyperoxia and respiratory acidosis developed during anaesthesia and slight hypotension was observed (minimum value 76 +/- 10 mm Hg at 40 mins), No changes were observed in dynorphin, beta-endorphin, ACTH, catecholamines and glucose, Plasma cortisol concentration increased from 220 +/- 17 basal to 354 +/- 22 nmol/L at 120 min during anaesthesia; plasma AVP concentration increased from 3 +/- 1 basal to 346 +/- 64 pmol/L at 100 min during anaesthesia and plasma lactate concentration increased from 1.22 +/- 0.08 basal to 1.76 +/- 0.13 mmol/L at 80 min during anaesthesia, Recovery was rapid and uneventful with ponies taking 46 +/- 6 min to stand. When midazolam/ketamine was compared with thiopentone or detomidine/ketamine for induction before halothane anaesthesia using an otherwise similar protocol in the same ponies, it caused slightly more respiratory depression, but less hypotension. Additionally, midazolam reduced the hormonal stress response commonly observed during halothane anaesthesia and appears to have a good potential for use in horses.