diabetestalk.net

Role Of Kidneys In Metabolic Acidosis

Renal Response To Metabolic Acidosis: Role Of Mrna Stabilization

Renal Response To Metabolic Acidosis: Role Of Mrna Stabilization

Renal response to metabolic acidosis: Role of mRNA stabilization Hend Ibrahim , Ph.D., Yeon J. Lee , Ph.D., and Norman P. Curthoys , Ph.D. Department of Biochemistry and Molecular Biology Colorado State University Fort Collins, CO 80523-1870 Direct Correspondence to: Dr. Norman P. Curthoys, Department of Biochemistry and Molecular Biology, Campus Delivery 1870, Colorado State University, Fort Collins, CO 80523-1870. Phone: (970) 491-3123, FAX: (970) 491-0494, [email protected] The publisher's final edited version of this article is available at Kidney Int See other articles in PMC that cite the published article. The renal response to metabolic acidosis is mediated, in part, by increased expression of the genes encoding key enzymes of glutamine catabolism and various ion transporters that contribute to the increased synthesis and excretion of ammonium ions and the net production and release of bicarbonate ions. The resulting adaptations facilitate the excretion of acid and partially restore systemic acid-base balance. Much of this response may be mediated by selective stabilization of the mRNAs that encode the responsive proteins. For example, the glutaminase mRNA contains a direct repeat of 8-nt AU-sequences that function as a pH-response element (pH-RE). This element is both necessary and sufficient to impart a pH-responsive stabilization to chimeric mRNAs. The pH-RE also binds multiple RNA binding proteins, including -crystallin, AUF1 and HuR. The onset of acidosis initiates an ER-stress response that leads to the formation of cytoplasmic stress granules. -crystallin is transiently recruited to the stress granules and concurrently, HuR is translocated from the nucleus to the cytoplasm. Based upon the cumulative data, a mechanism for the stabilization of Continue reading >>

Role Of The Kidneys In Maintaining Normal Blood Ph

Role Of The Kidneys In Maintaining Normal Blood Ph

Role of the kidneys in maintaining normal blood pH Summarized from Hamm L, Nakhoul N, Hering-Smith K. Acid-base homeostasis. Clin J Amer Soc Nephrology 2015; 10: 2232-42 The maintenance of blood pH within normal limits (7.35-7.45), called acid-base homeostasis, is a complex synergy involving three organs (lungs, kidneys and brain) as well as chemical buffers in blood and blood cells (erythrocytes). This vital physiologic process is the subject of a recent expert review article, authored by three academic/research nephrologists that focuses principally, although not exclusively, on the role of the kidney. The article begins with a broad overview of acid-base homeostasis, its pathophysiological importance and some familiar basic concepts such as bicarbonate buffering system and the related Henderson- Hasselbalch equation. The concept of metabolic/respiratory components of acid-base balance allows brief discussion of the integrated role of brain, lungs and kidneys. This introduction paves the way for the central focus of the article, which is the authors research interest: the role of the kidneys in acid-base homeostasis. In broad terms this role has two aspects that both relate to maintenance of normal blood bicarbonate (the metabolic component) concentration. The two aspects are: reabsorption to blood of virtually all bicarbonate filtered from blood by the kidneys; and generation of new bicarbonate that has been lost in buffering acid produced during normal cell metabolism. Most of this authoritative article is devoted to describing the complex detail of what is currently known about the multiple pathways involved in reabsorption and regeneration of bicarbonate, as well as secondary regulatory pathways. Although the main focus of the article is a detailed physiological Continue reading >>

Metabolic Acidosis

Metabolic Acidosis

Metabolic acidosis is a condition that occurs when the body produces excessive quantities of acid or when the kidneys are not removing enough acid from the body. If unchecked, metabolic acidosis leads to acidemia, i.e., blood pH is low (less than 7.35) due to increased production of hydrogen ions by the body or the inability of the body to form bicarbonate (HCO3−) in the kidney. Its causes are diverse, and its consequences can be serious, including coma and death. Together with respiratory acidosis, it is one of the two general causes of acidemia. Terminology : Acidosis refers to a process that causes a low pH in blood and tissues. Acidemia refers specifically to a low pH in the blood. In most cases, acidosis occurs first for reasons explained below. Free hydrogen ions then diffuse into the blood, lowering the pH. Arterial blood gas analysis detects acidemia (pH lower than 7.35). When acidemia is present, acidosis is presumed. Signs and symptoms[edit] Symptoms are not specific, and diagnosis can be difficult unless the patient presents with clear indications for arterial blood gas sampling. Symptoms may include chest pain, palpitations, headache, altered mental status such as severe anxiety due to hypoxia, decreased visual acuity, nausea, vomiting, abdominal pain, altered appetite and weight gain, muscle weakness, bone pain, and joint pain. Those in metabolic acidosis may exhibit deep, rapid breathing called Kussmaul respirations which is classically associated with diabetic ketoacidosis. Rapid deep breaths increase the amount of carbon dioxide exhaled, thus lowering the serum carbon dioxide levels, resulting in some degree of compensation. Overcompensation via respiratory alkalosis to form an alkalemia does not occur. Extreme acidemia leads to neurological and cardia Continue reading >>

Renal Compensation

Renal Compensation

Chronic Carbon Dioxide Retainer Renal compensation of respiratory acidosis is by increased urinary excretion of hydrogen ions and resorption of HCO3−. This relatively slow process occurs over several days. Slowly, pH reaches low normal values, but HCO3− levels and BE are increased. This is the situation of the patient with chronic respiratory failure. Pulmonary patients usually have chronic obstructive pulmonary disease or restrictive pulmonary disease, or they are morbidly obese. Increased Co2 stores are the rule, and the normal respiratory drive to Paco2 is obtunded. This group of patients is sensitive to O2 supplementation because respiratory drive is predominantly determined by hypoxemia. Patients with a Pao2 in the mid-50s and a Paco2 at the same level usually receive home O2 treatment, initially at night to reduce pulmonary hypertension and to relieve dyspnea. When the chronic Co2 retainer develops an acute respiratory problem and pH levels fall to less than 7.20, noninvasive ventilatory assistance is usually indicated. Fetoplacental Elimination of Metabolic Acid Load Fetal respiratory and renal compensation in response to changes in fetal pH is limited by the level of maturity and the surrounding maternal environment. However, although the placentomaternal unit performs most compensatory functions,3 the fetal kidneys have some, although limited, ability to contribute to the maintenance of fetal acid–base balance. The most frequent cause of fetal metabolic acidosis is fetal hypoxemia owing to abnormalities of uteroplacental function or blood flow (or both). Primary maternal hypoxemia or maternal metabolic acidosis secondary to maternal diabetes mellitus, sepsis, or renal tubular abnormalities is an unusual cause of fetal metabolic acidosis. Pregnant women, a Continue reading >>

Acid-base Balance Flashcards | Quizlet

Acid-base Balance Flashcards | Quizlet

Acid-base balance is an important determinant of protein ______ & ______ structure, function (When pH goes out of normal range these proteins are denatured ) All enzymatic functions are sensitive to this ion Relationship between respiratory system & acid-base balance -Determines affinity of Hb for O2, in alveolar capillaries - release in tissue capillaries -Respiratory rate directly affected by [H+] in resp center of brainstem + carotid body for rapid regulation of pH and pCO2 -Variations in alveolar ventilation volume cause acidosis and alkalosis Relationship b/w digestive system & acid-base balance -Acid in stomach hydrolyzes protein molecules -Digestive enzymes in stomach dependent on low pH to function (trypsin) -Alkaline secretions of biliary and pancreatic ducts neutralize gastric secretions -Enzymes in duodenum/sb act in a neutral pH environment (amylase lipase) Relationship b/w excretory system & acid-base balance -Acid , -Phos, -SO4 excreted from body by kidneys -Kidneys play role in long term (>24o) pH control -Rate of acid excretion dependent on degree of renal function and hormonal factors -At 37oC [H+] and [OH-] are both 100 nanomoles/L or 0.0000001 moles/L 7.35 to 7.45 (slightly alkaline not neutral) -Inversely related (negative in logarithm equation important) [H+] in plasma higher than normal (already slightly alkaline) quantity of Acid or Alkali required to return the plasma in-vitro to a normal pH (7.4) under standard conditions difference between commonly measured anions and cations i.e unmeasured anions such as lactate, oxalic acid increased in anion gap metabolic acidosis Role of intracellular and extracellular buffer, respiratory, and renal mechanisms in maintaining normal blood pH -Because the lungs can eliminate this it's called respiratory acid Continue reading >>

Pathogenesis, Consequences, And Treatment Of Metabolic Acidosis In Chronic Kidney Disease

Pathogenesis, Consequences, And Treatment Of Metabolic Acidosis In Chronic Kidney Disease

The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2018 UpToDate, Inc. All topics are updated as new evidence becomes available and our peer review process is complete. INTRODUCTION — Most individuals produce approximately 15,000 mmol (considerably more with exercise) of carbon dioxide and 50 to 100 meq of nonvolatile acid each day. Acid-base balance is maintained by normal elimination of carbon dioxide by the lungs (which affects the partial pressure of carbon dioxide [PCO2]) and normal excretion of nonvolatile acid by the kidneys (which affects the plasma bicarbonate concentration). The hydrogen ion concentration of the blood is determined by the ratio of the PCO2 and plasma bicarbonate concentration. (See "Simple and mixed acid-base disorders", section on 'Introduction'.) Acidosis associated with chronic kidney disease (CKD) will be discussed in this topic. An overview of simple acid-base disorders and renal tubular acidosis, as well as the approach to patients with metabolic acidosis, are presented elsewhere. (See "Simple and mixed acid-base disorders" and "Overview and pathophysiology of renal tubular acidosis and the effect on potassium balance" and "Approach to the adult with metabolic acidosis" and "Approach to the child with metabolic acidosis".) ACID-BASE BALANCE IN CHRONIC KIDNEY DISEASE — Acid-base balance is normally maintained by the renal excretion of the daily acid load (about 1 meq/kg per day, derived mostly from the generation of sulfuric acid during the metabolism of sulf Continue reading >>

Urine Ammonium, Metabolic Acidosis And Progression Of Chronic Kidney Disease

Urine Ammonium, Metabolic Acidosis And Progression Of Chronic Kidney Disease

Urine Ammonium, Metabolic Acidosis and Progression of Chronic Kidney Disease Pourafshar N.a · Pourafshar S.a · Soleimani M.b,c aDepartment of Medicine at University of Virginia, Charlottesville, VA, USA bDepartment of Medicine, University of Cincinnati, Cincinnati, OH, USA cDepartment of Medicine Services, Veterans Medical Center, Cincinnati, OH, USA The metabolism of a typical Western diet generates 50–100 mEq of acid (H+) per day, which must be excreted in the urine for the systemic acid-base to remain in balance. The 2 major mechanisms that are responsible for the renal elimination of daily acid under normal conditions are ammonium (NH4+) excretion and titratable acidity. In the presence of systemic acidosis, ammonium excretion is intensified and becomes the crucial mechanism for the elimination of acid. The impairment in NH4+ excretion is therefore associated with reduced acid excretion, which causes excess accumulation of acid in the body and consequently results in metabolic acidosis. Chronic kidney disease (CKD) is associated with the impairment in acid excretion and precipitation of metabolic acidosis, which has an adverse effect on the progression of CKD. Recent studies suggest that the progressive decline in renal ammonium excretion in CKD is an important determinant of the ensuing systemic metabolic acidosis and is an independent factor for predicting the worsening of kidney function. While these studies have been primarily performed in hypertensive individuals with CKD, a closer look at renal NH4+ excretion in non-hypertensive individuals with CKD is warranted to ascertain its role in the progression of kidney disease. The elimination of acid (H+) by kidney is the most crucial step in the maintenance of systemic acid-base homeostasis [ 1 , 2 ]. The rena Continue reading >>

Renal Function During Metabolic Acidosis

Renal Function During Metabolic Acidosis

Department of Animal Physiology and Cytobiology, Faculty of Biotechnology and Animal Husbandry, West Pomeranian University of Technology, Szczecin, Poland Metabolic acidosis influences renal structural and functional changes that occur to restore acid-base homeostasis. In this review selected aspects of these changes are discussed, focusing especially on alternations in tubular reabsorption and excretion, changes in water homeostasis and induction of hypertrophy. Also highlighted is the usage of proteomic techniques and gene expression analysis as useful tools which facilitate the obtaining of a wider view on changes in the kidneys during metabolic acidosis. MSc. in Biology, Department of AnimalPhysiology and Cytobiology, Faculty of Biotechnology and Animal Husbandry,West Pomeranian University of Technology, Doktora Judyma 6, 71-466 Szczecin,Poland. Barthwal MS: Analysis of arterial blood gases a comprehensive approach. J Assoc Physicians India 2004, 52, 573-577. Koeppen BM: Renal regulation of acid-base balance. Advan Physiol Educ 1998, 275, 132-141. Rutkowiak B: Zaburzenia trawienne i metaboliczne w stadach krow mlecznych. PWRiL, Warsaw 1987. Cheval L, Morla L, Elalouf JM, Doucet A: Kidney collecting duct acidbase regulon. Physiol Genomics 2006, 27, 271-281. Skrzypczak WF, Ogo M: Czynno nerek noworodka a homeostaza organizmu (Homeostasis and kidney function in the newborn.), cz. III. In: Stefaniak T (Red.): Noworodek a rodowisko. (Stafaniak T [Ed.]: The newborn and the environment, Part III. Wyd. UP, Wrocaw 2007, 111-132. Hamm LL, Simon EE: Roles and mechanisms of urinary buff er excretion. Am J Physiol Renal Physiol 1987, 253, 595-605. Huber TL: Lactic acidosis and renal function in sheep. J Anim Sci 1969, 29, 612-615. Yudkin J, Cohen RD, Slack B: The haemodynamic e Continue reading >>

Current Status Of Bicarbonate In Ckd

Current Status Of Bicarbonate In Ckd

Division of Nephrology and Hypertension, Case Western Reserve University, University Hospital Case Medical Center, Cleveland, Ohio Dr. Thomas H. Hostetter, Division of Nephrology and Hypertension, Case Western Reserve University, University Hospital Case Medical Center, 11100 Euclid Avenue, Cleveland, OH 44106. Email: Thomas.Hostetter{at}uhhospitals.org Metabolic acidosis was one of the earliest complications to be recognized and explained pathologically in patients with CKD. Despite the accumulated evidence of deleterious effects of acidosis, treatment of acidosis has been tested very little, especially with respect to standard clinical outcomes. On the basis of fundamental research and small alkali supplementation trials, correcting metabolic acidosis has a strikingly broad array of potential benefits. This review summarizes the published evidence on the association between serum bicarbonate and clinical outcomes. We discuss the role of alkali supplementation in CKD as it relates to retarding kidney disease progression, improving metabolic and musculoskeletal complications. Patients with CKD experience a multitude of abnormalities and disabilities, among which metabolic acidosis was one of the earliest complications to be recognized and explained pathologically. 1 4 In typical CKD, there is a direct correlation between the decline in GFR and the reduction in serum bicarbonate thought to be due primarily to the inability of the kidney to synthesize ammonia, regenerate bicarbonate, and excrete hydrogen ions. 5 In some instances, acid excretion is diminished earlier than usual in the course of GFR decline. Diseases in which this may be seen include obstructive nephropathy, sickle cell nephropathy, and occasionally in diabetic CKD. Epidemiologic studies have shown an ind Continue reading >>

Renal Regulation Of Metabolic Acidosis And Alkalosis

Renal Regulation Of Metabolic Acidosis And Alkalosis

1. 06/21/14 1 Normal Acid-Base Balance • Normal pH 7.35-7.45 • Narrow normal range • Compatible with life 6.8 - 8.0 ___/______/___/______/___ 6.8 7.35 7.45 8.0 Acid Alkaline 2. 06/21/14 2 PH Scale 3. 06/21/14 3 Acid & Base • Acid: • An acid is "when hydrogen ions accumulate in a solution" • It becomes more acidic • [H+] increases = more acidity • CO2 is an example of an acid. Base: A base is chemical that will remove hydrogen ions from the solution Bicarbonate is an example of a base. 4. 06/21/14 4 Acid and Base Containing Food: • To maintain health, the diet should consist of 60% alkaline forming foods and 40% acid forming foods. To restore health, the diet should consist of 80% alkaline forming foods and 20% acid forming foods. • Generally, alkaline forming foods include: most fruits, green vegetables, peas, beans, lentils, spices, herbs,seasonings,seeds and nuts. • Generally, acid forming foods include: meat, fish, poultry, eggs, grains, and legumes. 5. 06/21/14 5 Citric Acid And Lactic Acid Although both citric acid and lactic acid are acids BUT Citric acid leads to Alkalosis while Lactic acid to Acidosis due to metabolism 6. 06/21/14 6 Acidoses & Alkalosis • An abnormality in one or more of the pH control mechanisms can cause one of two major disturbances in Acid-BaseAcid-Base balance – AcidosisAcidosis – AlkalosisAlkalosis 7. 06/21/14 7 Acidosis • Acidosis is excessive blood acidity caused by an overabundance of acid in the blood or a loss of bicarbonate from the blood (metabolic acidosis), or by a buildup of carbon dioxide in the blood that results from poor lung function or slow breathing (respiratory acidosis). • Blood acidity increases when people ingest substances that contain or produce acid or when the lungs do not expel enou Continue reading >>

Acid/base Disorders: Metabolic Acidosis

Acid/base Disorders: Metabolic Acidosis

Are there clinical practice guidelines to inform decision-making? Does this patient have metabolic acidosis? Metabolic acidosis is generally defined by the presence of a low serum bicarbonate concentration (normal range 22-28 mEq/L), although occasionally states can exist where the serum bicarbonate is normal with an elevated anion gap (e.g., patients with a lactic acidosis who have received a bicarbonate infusion or patients on hemodialysis). In general, a metabolic acidosis is associated with a low urine pH but depending on the presence or absence of a respiratory alkalosis, this may also be normal or elevated. Thus, a patient can have an acidosis but not be acidemic. Metabolic acidoses occur when there is excess acid in the plasma. In the basal state, the body generates about 12,000 to 13,000 mmol of carbon dioxide (CO2), and 1-1.5 mmol per kilogram body weight of nonvolatile acid. The body has a large buffering capacity, with CO2-HCO3 as the major buffer system. The two major routes of acid excretion are the lungs (for CO2) and the kidneys (for nonvolatile acids) A metabolic acidosis can be caused by three major mechanisms: 1) increased acid production; 2) bicarbonate loss; and 3) decreased renal acid excretion Increased acid production leads to anion-gap (AG) metabolic acidosis, and involves a variety of different clinical processes, see An anion gap acidosis may also result for ingestion of an acid load. Both bicarbonate loss and decreased renal acid excretion lead to normal-anion gap (NG) metabolic acidosis. When there is HCO3 loss, chloride is retained to maintain electrical neutrality. The different clinical processes are summarized in Toxic ingestions are common causes of AG metabolic acidosis. The commonest causes are methanol and ethylene glycol intoxicatio Continue reading >>

Metabolic Acidosis

Metabolic Acidosis

Practice Essentials Metabolic acidosis is a clinical disturbance characterized by an increase in plasma acidity. Metabolic acidosis should be considered a sign of an underlying disease process. Identification of this underlying condition is essential to initiate appropriate therapy. (See Etiology, DDx, Workup, and Treatment.) Understanding the regulation of acid-base balance requires appreciation of the fundamental definitions and principles underlying this complex physiologic process. Go to Pediatric Metabolic Acidosis and Emergent Management of Metabolic Acidosis for complete information on those topics. Continue reading >>

How The Kidneys Regulate Acid Base Balance

How The Kidneys Regulate Acid Base Balance

Acid-Base Balance Everyday processes like walking, the digestion of food, and the overall metabolism in your body produce a lot of acid as a byproduct. Because of this, you'd be a giant walking lemon if it wasn't for your kidneys. What I mean is, like a lemon, you'd be filled with acid if your kidneys weren't there to help you regulate your body's pH through something we call acid-base balance. This is a process whereby receptors are able to determine the pH of your body and blood and do something about it if it's too acidic or too basic. If an imbalance in the pH is detected by your lungs, buffers, or kidneys, your body springs into action to take care of the problem. In this lesson, we'll focus in on how the kidneys help to control the acid-base balance in your body. Protons and Buffers Whereas the buffers in your body and your lungs are involved in the rapid adjustment of your blood's pH, the kidneys adjust the pH more slowly. Under normal conditions, the kidney's main role in acid-base balance is through the excretion of acid in the form of hydrogen (H+) ions. The kidneys secrete excess hydrogen ions primarily in the proximal tubule. The interesting thing to note is that while the proximal tubule secretes a lot of acid, the tubular fluid's pH remains virtually unchanged. This is because buffers filtered by the glomerulus, including phosphate and bicarbonate, help to minimize the acidity of the tubular fluid. In fact, what's really cool is that the pH of the tubular fluid, by the time it reaches the collecting duct, is about 7.4, which is exactly the pH of normal blood. The Collecting Duct However, by the time urine is excreted out of the body, it can be acidic, basic, or neutral. This is because the end-all, be-all gatekeeper in determining the final pH of urine is Continue reading >>

Metabolic Acidosis And The Progression Of Chronic Kidney Disease

Metabolic Acidosis And The Progression Of Chronic Kidney Disease

Abstract Metabolic acidosis is a common complication of chronic kidney disease. Accumulating evidence identifies acidosis not only as a consequence of, but as a contributor to, kidney disease progression. Several mechanistic pathways have been identified in this regard. The dietary acid load, even in the absence of overt acidosis, may have deleterious effects. Several small trials now suggest that the treatment of acidosis with oral alkali can slow the progression of kidney disease. Keywords BicarbonateDietary acidNet endogenous acid productionSodium bicarbonateAlkaliAmmoniaComplementEndothelinAldosterone Review Metabolic acidosis is a common complication of chronic kidney disease (CKD). Based on a cross-sectional analysis of the National Health and Nutrition Examination Survey, an estimated 26 million adults in the United States have CKD, and approximately 700,000 individuals have an estimated glomerular filtration rate (eGFR) less than 30 mL/min/1.73 m2[1]. As 30-50% of those with eGFR <30 mL/min/1.73 m2 have metabolic acidosis [2–4], approximately 200,000 to 350,000 individuals with CKD stage 4 and 5 have chronic metabolic acidosis in the United States. Chronic metabolic acidosis may have various adverse effects in patients with CKD, including altered skeletal metabolism [5], insulin resistance [6], protein-energy wasting [7–9], and accelerated progression of kidney disease. In epidemiologic studies, low serum bicarbonate levels have been associated with high mortality (Table 1). In a study of 1,240 male patients with non-dialysis dependent CKD, the lowest mortality was observed among those with baseline serum bicarbonate levels of 26–29 mEq/L, whereas patients with levels <22 mEq/L had a 43% higher risk of mortality [10]. Using data from the African American S Continue reading >>

Metabolic Acidosis And Kidney Disease: Does Bicarbonate Therapy Slow The Progression Of Ckd?

Metabolic Acidosis And Kidney Disease: Does Bicarbonate Therapy Slow The Progression Of Ckd?

Metabolic acidosis and kidney disease: does bicarbonate therapy slow the progression of CKD? Correspondence and offprint requests to: Csaba P. Kovesdy; E-mail: [email protected] Search for other works by this author on: Nephrology Dialysis Transplantation, Volume 27, Issue 8, 1 August 2012, Pages 30563062, Csaba P. Kovesdy; Metabolic acidosis and kidney disease: does bicarbonate therapy slow the progression of CKD?, Nephrology Dialysis Transplantation, Volume 27, Issue 8, 1 August 2012, Pages 30563062, Metabolic acidosis is a common complication associated with progressive loss of kidney function. The diminishing ability of the kidneys to maintain acidbase homeostasis results in acid accumulation, leading to various complications such as impairment in nutritional status, worsened uremic bone disease and an association with increased mortality. In addition to these adverse effects which are related to acid retention, metabolic acidosis may also cause kidney damage, possibly through the stimulation of adaptive mechanisms aimed at maintaining acidbase homeostasis in the face of decreasing kidney function. Recent clinical trials have suggested that correction or prevention of metabolic acidosis by alkali administration is able to attenuate kidney damage and to slow progression of chronic kidney disease (CKD), and may hence offer an effective, safe and affordable renoprotective strategy. We review the physiology and pathophysiology of acidbase homeostasis in CKD, the mechanisms whereby metabolic acidosis may be deleterious to kidney function, and the results of clinical trials suggesting a benefit of alkali therapy, with special attention to details related to the practical implementation of the results of these trials. bicarbonate , chronic kidney disease , metabolic ac Continue reading >>

More in ketosis