Carbohydrate metabolism

From Wikipedia, the free encyclopedia Carbohydrate metabolism denotes the various biochemical processes responsible for the formation, breakdown and interconversion of carbohydrates in living organisms. The most important carbohydrate is glucose, a simple sugar (monosaccharide) that is metabolized by nearly all known organisms. Glucose and other carbohydrates are part of a wide variety of metabolic pathways across species: plants synthesize carbohydrates from carbon dioxide and water by photosynthesis storing the absorbed energy internally, often in the form of starch or lipids. Plant components are consumed by animals and fungi, and used as fuel for cellular respiration. Oxidation of one gram of carbohydrate yields approximately 4 kcal of energy and from lipids about 9 kcal. Energy obtained from metabolism (e.g. oxidation of glucose) is usually stored temporarily within cells in the form of ATP. Organisms capable of aerobic respiration metabolize glucose and oxygen to release energy with carbon dioxide and water as byproducts. Carbohydrates can be chemically divided into complex and simple.[1] Simple carbohydrates consist of single or double sugar units (monosaccharides and disaccharides, respectively). Sucrose or table sugar (a disaccharide) is a common example of a simple carbohydrate. Complex carbohydrates contain three or more sugar units linked in a chain. They are digested by enzymes to release the simple sugars. Starch, for example, is a polymer of glucose units and is typically broken down to glucose. Simple and complex carbohydrates are digested at similar rates, so the distinction is not very useful for distinguishing nutritional quality.[1] Cellulose is also a polymer of glucose but it cannot be digested by most organisms. Some bacteria that produce enzymes for cellulose live inside the gut of some mammals such as cows, and when cows eat plants, the cellulose is broken down by the bacteria and some of it is released into the gut. Carbohydrates are a superior short-term fuel for organisms because they are simpler to metabolize than fats or those amino acids (components of proteins) that can be used for fuel. In animals, the most important carbohydrate is glucose. The concentration of glucose in the blood is used as the main control for the central metabolic hormone, insulin. Starch, and cellulose in a few organisms (e.g., some animals (such as termites[2]) and some microorganisms (such as protists and bacteria), both being glucose polymers, are disassembled during digestion and absorbed as glucose. Some simple carbohydrates have their own enzymatic oxidation pathways, as do only a few of the more complex carbohydrates. The disaccharide lactose, for instance, requires the enzyme lactase to be broken into its monosaccharides components; many animals lack this enzyme in adulthood.

Carbohydrates are typically stored as long polymers of glucose molecules with glycosidic bonds for structural support (e.g. chitin, cellulose) or for energy storage (e.g. glycogen, starch). However, the strong affinity of most carbohydrates for water makes storage of large quantities of carbohydrates inefficient due to the large molecular weight of the solvated water-carbohydrate complex. In most organisms, excess carbohydrates are regularly catabolised to form acetyl-CoA, which is a feed stock for the fatty acid synthesis pathway; fatty acids, triglycerides, and other lipids are commonly used for long-term energy storage. The hydrophobic character of lipids makes them a much more compact form of energy storage than hydrophilic carbohydrates. However, animals, including humans, lack the necessary enzymatic machinery and so do not synthesize glucose from lipids, though glycerol can be converted to glucose.[3] All carbohydrates share a general formula of approximately CnH2nOn; glucose is C6H12O6. Monosaccharides may be chemically bonded together to form disaccharides such as sucrose and longer polysaccharides such as starch and cellulose.Contents [hide] 1 Catabolism 2 Metabolic pathways 3 Glucoregulation 4 Human diseases of carbohydrate metabolism 5 References 6 External links [edit] Catabolism Main article: Carbohydrate catabolism Oligo/polysaccharides are typically cleaved into smaller monosaccharides by enzymes called glycoside hydrolases. The monosaccharide units then enter monosaccharide catabolism. Organisms vary in the range of monosaccharides they can absorb and use, and also in the range of more complex carbohydrates they are capable of disassembling. [edit] Metabolic pathways Carbon fixation, or photosynthesis, in which CO2 is reduced to carbohydrate.

Glycolysis - the oxidation metabolism of glucose molecules to obtain ATP and pyruvate Pyruvate from glycolysis enters the Krebs cycle, also known as the citric acid cycle, in aerobic organisms after moving through pyruvate dehydrogenase complex. The pentose phosphate pathway, which acts in the conversion of hexoses into pentoses and in NADPH regeneration. Glycogenesis - the conversion of excess glucose into glycogen as a cellular storage mechanism; this prevents excessive osmotic pressure buildup inside the cell Glycogenolysis - the breakdown of glycogen into glucose, which provides a glucose supply for glucose-dependent tissues. Gluconeogenesis - de novo synthesis of glucose molecules from simple organic compounds. an example in humans is the conversion of a few amino acids in cellular protein to glucose. Metabolic use of glucose is highly important as an energy source for muscle cells and in the brain, and red blood cells. [edit] Glucoregulation Glucoregulation is the maintenance of steady levels of glucose in the body; it is part of homeostasis, and so keeps a constant internal environment around cells in the body. The hormone insulin is the primary regulatory signal in animals, suggesting that the basic mechanism is very old and very central to animal life. When present, it causes many tissue cells to take up glucose from the circulation, causes some cells to store glucose internally in the form of glycogen, causes some cells to take in and hold lipids, and in many cases controls cellular electrolyte balances and amino acid uptake as well. Its absence turns off glucose uptake into cells, reverses electrolyte adjustments, begins glycogen breakdown and glucose release into the circulation by some cells, begins lipid release from lipid storage cells, etc. The level of circulatory glucose (known informally as "blood sugar") is the most important signal to the insulin-producing cells. Because the level of circulatory glucose is largely determined by the intake of dietary carbohydrates, diet controls major aspects of metabolism via insulin. In humans, insulin is made by beta cells in the pancreas, fat is stored in adipose tissue cells, and glycogen is both stored and released as needed by liver cells. Regardless of insulin levels, no glucose is released to the blood from internal glycogen stores from muscle cells.

The hormone glucagon, on the other hand, has an effect opposite to that of insulin, forcing the conversion of glycogen in liver cells to glucose, which is then released into the blood. Muscle cells, however, lack the ability to export glucose into the blood. The release of glucagon is precipitated by low levels of blood glucose. Other hormones, notably growth hormone, cortisol, and certain catecholamines (such as epinepherine) have glucoregulatory actions similar to glucagon. [edit] Human diseases of carbohydrate metabolism Diabetes mellitus Lactose intolerance Fructose intolerance Galactosemia Glycogen storage disease

Lipid metabolism
Lipid metabolism refers to the processes that involve the intercourse and degradation of lipids.

The types of lipids involved include: Bile salts Cholesterols Eicosanoids Glycolipids Ketone bodies Fatty acids - see also fatty acid metabolism Phospholipids Sphingolipids Steroid - see also steroidogenesis Triacylglycerols (fats) - see also lipolysis and lipogenesis

Lipoprotein
A lipoprotein is a biochemical assembly that contains both proteins and lipids, bound to the proteins, which allow fats to move through the water inside and outside cells. The proteins serve to emulsify the lipid (otherwise called fat) molecules. Many enzymes, transporters, structural proteins, antigens, adhesins, and toxins are lipoproteins. Examples include the highdensity (HDL) and low-density (LDL) lipoproteins, which enable fats to be carried in the blood stream, the transmembrane proteins of the mitochondrion and the chloroplast, and bacterial lipoproteins.[1]
Function

The function of lipoprotein particles is to transport lipids (fats) (such as triacylglycerol) around the body in the blood.

All cells use and rely on fats and cholesterol as building-blocks to create the multiple membranes that cells use both to control internal water content and internal water-soluble elements and to organize their internal structure and protein enzymatic systems.

The lipoprotein particles have hydrophilic groups of phospholipids, cholesterol, and apoproteins directed outward. Such characteristics make them soluble in the salt water-based blood pool. Triglyceride-fats and cholesterol esters are carried internally, shielded from the water by the phospholipid monolayer and the apoproteins.

The interaction of the proteins forming the surface of the particles (a) with enzymes in the blood, (b) with each other, and (c) with specific proteins on the surfaces of cells determine whether triglycerides and cholesterol will be added to or removed from the lipoprotein transport particles.

Regarding atheroma development and progression as opposed to regression, the key issue has always been cholesterol transport patterns, not cholesterol concentration itself.[citation needed] [edit] Transmembrane lipoproteins

The lipids are often an essential part of the complex, even if they seem to have no catalytic activity by themselves. To isolate transmembrane lipoproteins from their associated membranes, detergents are often needed. [edit] Classification [edit] By density

Lipoproteins may be classified as follows, listed from larger and less dense to smaller and denser. Lipoproteins are larger and less dense when the fat to protein ratio is increased. They are classified on the basis of electrophoresis and ultracentrifugation. Chylomicrons carry triglycerides (fat) from the intestines to the liver, to skeletal muscle, and to adipose tissue. Very-low-density lipoproteins (VLDL) carry (newly synthesised) triglycerides from the liver to adipose tissue. Intermediate-density lipoproteins (IDL) are intermediate between VLDL and LDL. They are not usually detectable in the blood. Low-density lipoproteins (LDL) carry cholesterol from the liver to cells of the body. LDLs are sometimes referred to as the "bad cholesterol" lipoprotein. High-density lipoproteins (HDL) collect cholesterol from the body's tissues, and take it back to the liver. HDLs are sometimes referred to as the "good cholesterol" lipoprotein.

.Density (g/mL) Class Diameter (nm) phospholipid % triacylglycerol

% protein

% cholesterol

& cholesterol ester >1.063 HDL 515 33 1828 25 2550 18 30 50 29 22 29 21 22 18 <2 4 8 31 50 8 7 84

1.0191.063 LDL 1.0061.019 IDL

0.951.006 VLDL 3080 10 <0.95 Chylomicrons

100-1000

[2] [edit] Alpha and beta

It is also possible to classify lipoproteins as "alpha" and "beta", according to the classification of proteins in serum protein electrophoresis. This terminology is sometimes used in describing lipid disorders such as Abetalipoproteinemia. [edit] Lipoprotein(a)

Lipoprotein(a) Lp(a), Cardiology diagnostic tests < 14 mg/dL : Normal 14-19 mg/dL : ? > 19 mg/dL : High risk

How to lower: aerobic exercise, niacin, aspirin, guggulipid.[3] Further information: Lipoprotein(a) [edit] Metabolism

The handling of lipoproteins in the body is referred to as lipoprotein metabolism. It is divided into two pathways, exogenous and endogenous, depending in large part on whether the lipoproteins in question are composed chiefly of dietary (exogenous) lipids or whether they originated in the liver (endogenous). [edit] Exogenous pathway

Epithelial cells lining the small intestine readily absorb lipids from nutritive substances. These lipids, including triglycerides, phospholipids, and cholesterol, are assembled with apolipoprotein B-48 into chylomicrons. These nascent chylomicrons are secreted from the intestinal epithelial cells into the lymphatic circulation in a process that depends heavily on apolipoprotein B-48. As they circulate through the lymphatic vessels, nascent chylomicrons bypass the liver circulation and are drained via the thoracic duct into the bloodstream.

In the bloodstream, HDL particles donate apolipoprotein C-II and apolipoprotein E to the nascent chylomicron; the chylomicron is now considered mature. Via apolipoprotein C-II, mature chylomicrons activate lipoprotein lipase (LPL), an enzyme on endothelial cells lining the blood vessels. LPL catalyzes the hydrolysis of triacylglycerol (i.e., glycerol covalently joined to three fatty acids) that ultimately releases glycerol and fatty acids from the chylomicrons. Glycerol and fatty acids can then be absorbed in peripheral tissues, especially adipose and muscle, for energy and storage.

The hydrolyzed chylomicrons are now considered chylomicron remnants. The chylomicron remnants continue circulating until they interact via apolipoprotein E with chylomicron remnant receptors, found chiefly in the liver. This interaction causes the endocytosis of the chylomicron remnants, which are subsequently hydrolyzed within lysosomes. Lysosomal hydrolysis releases glycerol and fatty acids into the cell, which can be used for energy or stored for later use. [edit] Endogenous pathway

The liver is another important source of lipoproteins, principally VLDL. Triacylglycerol and cholesterol are assembled with apolipoprotein B-100 to form VLDL particles. Nascent VLDL particles are released into the bloodstream via a process that depends upon apolipoprotein B-100.

As in chylomicron metabolism, the apolipoprotein C-II and apolipoprotein E of VLDL particles are acquired from HDL particles. Once loaded with apolipoproteins C-II and E, the nascent VLDL particle is considered mature.

Again like chylomicrons, VLDL particles circulate and encounter LPL expressed on endothelial cells. Apolipoprotein C-II activates LPL, causing hydrolysis of the VLDL particle and the release of glycerol and fatty acids. These products can be absorbed from the blood by peripheral tissues, principally adipose and muscle. The hydrolyzed VLDL particles are now called VLDL remnants or intermediate-density lipoproteins (IDLs). VLDL remnants can circulate and, via an interaction between apolipoprotein E and the remnant receptor, be absorbed by the liver, or they can be further hydrolyzed by hepatic lipase.

Hydrolysis by hepatic lipase releases glycerol and fatty acids, leaving behind IDL remnants, called low-density lipoproteins (LDL), which contain a relatively high cholesterol content ( [4] see native LDL structure at 37C on YouTube). LDL circulates and is absorbed by the liver and peripheral cells. Binding of LDL to its target tissue occurs through an interaction between the LDL receptor and apolipoprotein B-100 or E on the LDL particle. Absorption occurs through endocytosis, and the internalized LDL particles are hydrolyzed within lysosomes, releasing lipids, chiefly cholesterol.

Metabolic acidosis
In medicine, metabolic acidosis is a condition that occurs when the body produces too much 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 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 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. [edit] Signs and symptoms

Symptoms are non-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 (either loss of or increased) and weight loss (longer term), muscle weakness and bone pains. 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. Over compensation via respiratory alkalosis to form an alkalemia does not occur.

Extreme acidemia leads to neurological and cardiac complications: Neurological: lethargy, stupor, coma, seizures. Cardiac: arrhythmias (ventricular tachycardia), decreased response to epinephrine; both lead to hypotension (low blood pressure).

Physical examination occasionally reveals signs of disease, but is otherwise normal. Cranial nerve abnormalities are reported in ethylene glycol poisoning, and retinal edema can be a sign of methanol (methyl alcohol) intoxication. Longstanding chronic metabolic acidosis leads to osteoporosis and can cause fractures.

[edit] Diagnosis

Arterial blood gas sampling is essential for the diagnosis. If the pH is low (under 7.35) and the bicarbonate levels are decreased (<24 mmol/l), metabolic acidemia is present, and metabolic acidosis is presumed. Due to respiratory compensation (hyperventilation), carbon dioxide is decreased and conversely oxygen is increased. An ECG can be useful to anticipate cardiac complications.

Other tests that are relevant in this context are electrolytes (including chloride), glucose, renal function and a full blood count. Urinalysis can reveal acidity (salicylate poisoning) or alkalinity (renal tubular acidosis type I). In addition, it can show ketones in ketoacidosis.

To distinguish between the main types of metabolic acidosis, a clinical tool called the anion gap is considered very useful. It is calculated by subtracting the chloride and bicarbonate levels from the sodium.

Anion gap = ( [Na+]+ [K+]) - ( [Cl-]+[HCO3-] )

As sodium is the main extracellular cation, and chloride and bicarbonate are the main anions, the result should reflect the remaining anions. Normally, this concentration is about 8-16 mmol/l (124). An elevated anion gap (i.e. > 16 mmol/l) can indicate particular types of metabolic acidosis, particularly certain poisons, lactate acidosis and ketoacidosis.

As the differential diagnosis is made, certain other tests may be necessary, including toxicological screening and imaging of the kidneys. It is also important to differentiate between acidosis-induced hyperventilation and asthma; otherwise, treatment could lead to inappropriate bronchodilation.[1]

[edit] Causes

Metabolic acidosis occurs when the body produces too much acid, or when the kidneys are not removing enough acid from the body. There are several types of metabolic acidosis. The main causes are best grouped by their influence on the anion gap.

It bears noting that the anion gap can be spuriously normal in sampling errors of the sodium level, e.g. in extreme hypertriglyceridemia. The anion gap can be increased due to relatively low levels of cations other than sodium and potassium (e.g. calcium or magnesium). [edit] Increased anion gap Main article: High anion gap metabolic acidosis

Causes include: lactic acidosis ketoacidosis chronic renal failure (accumulation of sulfates, phosphates, urea) intoxication: organic acids (salicylates, ethanol, methanol, formaldehyde, ethylene glycol, paraldehyde, INH) sulfates, metformin (Glucophage) massive rhabdomyolysis [edit] Normal anion gap

Main article: Normal anion gap acidosis

Causes include:[1] longstanding diarrhea (bicarbonate loss) pancreatic fistula uretero-sigmoidostomy Renal tubular acidosis (RTA) intoxication: ammonium chloride acetazolamide (Diamox) bile acid sequestrants isopropyl alcohol renal failure (occasionally) inhalant abuse toluene [edit] Pathophysiology [edit] Compensatory mechanisms

Metabolic acidosis is either due to increased generation of acid or an inability to generate sufficient bicarbonate. The body regulates the acidity of the blood by four buffering mechanisms. bicarbonate buffering system Intracellular buffering by absorption of hydrogen atoms by various molecules, including proteins, phosphates and carbonate in bone.

Respiratory compensation Renal compensation [edit] Buffer

The decreased bicarbonate that distinguishes metabolic acidosis is therefore due to two separate processes: the buffer (from water and carbon dioxide) and additional renal generation. The buffer reactions are:

The Henderson-Hasselbalch equation mathematically describes the relationship between blood pH and the components of the bicarbonate buffering system:

Using Henry's Law, we can say that [CO2]=0.03xPaCO2 (PaCO2 is the pressure of CO2 in arterial blood) Adding the other normal values, we get

[edit] Treatment

A pH under 7.1 is an emergency, due to the risk of cardiac arrhythmias, and may warrant treatment with intravenous bicarbonate. Bicarbonate is given at

50-100 mmol at a time under scrupulous monitoring of the arterial blood gas readings. This intervention, however, has some serious complications in lactic acidosis and, in those cases, should be use with great care.

If the acidosis is particularly severe and/or there may be intoxication, consultation with the nephrology team is considered useful, as dialysis may clear both the intoxication and the acidosis.

Metabolic alkalosis
Metabolic alkalosis is a metabolic condition in which the pH of tissue is elevated beyond the normal range ( 7.35-7.45 ). This is the result of decreased hydrogen ion concentration, leading to increased bicarbonate, or alternatively a direct result of increased bicarbonate concentrations. Terminology Alkalosis refers to a process by which the pH is increased. Alkalemia refers to a pH which is higher than normal, specifically in the blood. [edit] Causes

The causes of metabolic alkalosis can be divided into two categories, depending upon urine chloride levels.[1] [edit] Chloride-responsive (<10 mEq/L) Loss of hydrogen ions - Most often occurs via two mechanisms, either vomiting or via the kidney. Vomiting results in the loss of hydrochloric acid (hydrogen and chloride ions) with the stomach contents. In the hospital setting this can commonly occur from nasogastric suction tubes.

Severe vomiting also causes loss of potassium (hypokalaemia) and sodium (hyponatraemia). The kidneys compensate for these losses by retaining sodium in the collecting ducts at the expense of hydrogen ions (sparing sodium/potassium pumps to prevent further loss of potassium), leading to metabolic alkalosis.[2] Congenital chloride diarrhea - rare for being a diarrhea that causes alkalosis instead of acidosis. Contraction alkalosis - This results from a loss of water in the extracellular space which is poor in bicarbonate, typically from diuretic use. Since water is lost while bicarbonate is retained, the increased concentration of bicarbonate "mops up" more of the hydrogen ions and raises the blood pH. Diuretic therapy - loop diuretics and thiazides can both initially cause increase in chloride, but once stores are depleted, urine excretion will be below < 25 mEq/L. The loss of fluid from sodium excretion causes a contraction alkalosis. Posthypercapnia - Hypoventilation (decreased respiratory rate) causes hypercapnia (increased levels of CO2), which results in respiratory acidosis. Renal compensation with excess bicarbonate occurs to lessen the effect of the acidosis. Once carbon dioxide levels return to base line, the higher bicarbonate levels reveal themselves putting the patient into metabolic alkalosis. Cystic Fibrosis [edit] Chloride-resistant (>20 mEq/L) Retention of bicarbonate Shift of hydrogen ions into intracellular space - Seen in hypokalemia. Due to a low extracellular potassium concentration, potassium shifts out of the cells. In order to maintain electrical neutrality, hydrogen shifts into the cells, raising blood pH. Alkalotic agents - Alkalotic agents, such as bicarbonate (administrated in cases of peptic ulcer or hyperacidity) or antacids, administered in excess can lead to an alkalosis.

Hyperaldosteronism - Renal loss of hydrogen ions occurs when excess aldosterone (Conn's syndrome) increases the activity of a sodium-hydrogen exchange protein in the kidney. This increases the retention of sodium ions whilst pumping hydrogen ions into the renal tubule. Excess sodium increases extracellular volume and the loss of hydrogen ions creates a metabolic alkalosis. Later, the kidney responds through the aldosterone escape to excrete sodium and chloride in urine.[3] Excess Glycyrrhizin consumption Bartter syndrome and Gitelman syndrome - syndromes with presentations analogous to taking diuretics characterized with normotensive patients Liddle syndrome - a syndrome from defect sodium channel deletion characterized by hypertension and hypoaldosteronism. 11-hydroxylase deficiency and 17-hydroxylase deficiency - both characterized by hypertension [edit] Compensation

Compensation for metabolic alkalosis occurs mainly in the lungs, which retain carbon dioxide (CO2) through slower breathing, or hypoventilation (respiratory compensation). CO2 is then consumed toward the formation of the carbonic acid intermediate, thus decreasing pH. Respiratory compensation, though, is incomplete. The decrease in [H+] suppresses the peripheral chemoreceptors, which are sensitive to pH. But, because respiration slows, there's an increase in PCO2 which would cause an offset of the depression because of the action of the central chemoreceptors which are sensitive to the partial pressure of CO2[citation needed] in the cerebral spinal fluid. So, because of the central chemoreceptors, respiration rate would be increased.

Renal compensation for metabolic alkalosis, less effective than respiratory compensation, consists of increased excretion of HCO3- (bicarbonate), as the filtered load of HCO3- exceeds the ability of the renal tubule to reabsorb it.

Respiratory acidosis

Respiratory acidosis is a medical condition in which decreased ventilation (hypoventilation) causes increased blood carbon dioxide concentration and decreased pH (a condition generally called acidosis). Carbon dioxide is produced constantly as the body's cells respire, and this CO2 will accumulate rapidly if the lungs do not adequately expel it through alveolar ventilation. Alveolar hypoventilation thus leads to an increased PaCO2 (called hypercapnia). The increase in PaCO2 in turn decreases the HCO3/PaCO2 ratio and decreases pH. Terminology Acidosis refers to disorders that lower arterial pH to < 7.35. Acidemia refers to a arterial pH < 7.35. [edit] Types of respiratory acidosis

Respiratory acidosis can be acute or chronic. In acute respiratory acidosis, the PaCO2 is elevated above the upper limit of the reference range (over 6.3 kPa or 47 mm Hg) with an accompanying acidemia (pH <7.35). In chronic respiratory acidosis, the PaCO2 is elevated above the upper limit of the reference range, with a normal blood pH (7.35 to 7.45) or near-normal pH secondary to renal compensation and an elevated serum bicarbonate (HCO3 >30 mm Hg). [edit] Causes [edit] Acute

Acute respiratory acidosis occurs when an abrupt failure of ventilation occurs. This failure in ventilation may be caused by depression of the central respiratory center by cerebral disease or drugs, inability to ventilate

adequately due to neuromuscular disease (e.g., myasthenia gravis, amyotrophic lateral sclerosis, Guillain-Barr syndrome, muscular dystrophy), or airway obstruction related to asthma or chronic obstructive pulmonary disease (COPD) exacerbation. [edit] Chronic

Chronic respiratory acidosis may be secondary to many disorders, including COPD. Hypoventilation in COPD involves multiple mechanisms, including decreased responsiveness to hypoxia and hypercapnia, increased ventilation-perfusion mismatch leading to increased dead space ventilation, and decreased diaphragm function secondary to fatigue and hyperinflation.

Chronic respiratory acidosis also may be secondary to obesity hypoventilation syndrome (i.e., Pickwickian syndrome), neuromuscular disorders such as amyotrophic lateral sclerosis, and severe restrictive ventilatory defects as observed in interstitial fibrosis and thoracic deformities.

Lung diseases that primarily cause abnormality in alveolar gas exchange usually do not cause hypoventilation but tend to cause stimulation of ventilation and hypocapnia secondary to hypoxia. Hypercapnia only occurs if severe disease or respiratory muscle fatigue occurs. [edit] Physiological response [edit] Mechanism

Metabolism rapidly generates a large quantity of volatile acid (H2CO3) and nonvolatile acid. The metabolism of fats and carbohydrates leads to the formation of a large amount of CO2. The CO2 combines with H2O to form

carbonic acid (H2CO3). The lungs normally excrete the volatile fraction through ventilation, and acid accumulation does not occur. A significant alteration in ventilation that affects elimination of CO2 can cause a respiratory acid-base disorder. The PaCO2 is maintained within a range of 39-41 mm Hg in normal states.

Alveolar ventilation is under the control of the central respiratory centers, which are located in the pons and the medulla. Ventilation is influenced and regulated by chemoreceptors for PaCO2, PaO2, and pH located in the brainstem,and in the aortic and carotid bodies as well as by neural impulses from lung stretch receptors and impulses from the cerebral cortex. Failure of ventilation quickly increases the PaCO2.

In acute respiratory acidosis, compensation occurs in 2 steps. The initial response is cellular buffering that occurs over minutes to hours. Cellular buffering elevates plasma bicarbonate (HCO3) only slightly, approximately 1 mEq/L for each 10-mm Hg increase in PaCO2. The second step is renal compensation that occurs over 3-5 days. With renal compensation, renal excretion of carbonic acid is increased and bicarbonate reabsorption is increased. For instance, PEPCK is upregulated in renal proximal tubule brush border cells, in order to secrete more NH3 and thus to produce more HCO3.[1] [edit] Estimated changes

In renal compensation, plasma bicarbonate rises 3.5 mEq/L for each increase of 10 mm Hg in PaCO2. The expected change in serum bicarbonate concentration in respiratory acidosis can be estimated as follows: Acute respiratory acidosis: HCO3 increases 1 mEq/L for each 10 mm Hg rise in PaCO2. Chronic respiratory acidosis: HCO3 rises 3.5 mEq/L for each 10 mm Hg rise in PaCO2.

The expected change in pH with respiratory acidosis can be estimated with the following equations: Acute respiratory acidosis: Change in pH = 0.008 X (40 PaCO2) Chronic respiratory acidosis: Change in pH = 0.003 X (40 PaCO2)

Respiratory acidosis does not have a great effect on electrolyte levels. Some small effects occur on calcium and potassium levels. Acidosis decreases binding of calcium to albumin and tends to increase serum ionized calcium levels. In addition, acidemia causes an extracellular shift of potassium, but respiratory acidosis rarely causes clinically significant hyperkalemia.

Respiratory alkalosis
Respiratory alkalosis is a medical condition in which increased respiration (hyperventilation) elevates the blood pH (a condition generally called alkalosis). It is one of four basic categories of disruption of acid-base homeostasis. Terminology Alkalosis refers to disorders that elevate arterial pH to > 7.45. Alkalemia refers to a arterial pH > 7.45. [edit] Types

There are two types of respiratory alkalosis: chronic and acute. Acute respiratory alkalosis occurs rapidly. For every 10 mmHg drop in PCO2 in arterial blood, there is a corresponding 2 mEq/L drop in bicarbonate ion due to acute compensation. During acute respiratory alkalosis, the person may lose consciousness where the rate of ventilation will resume to normal.

Chronic respiratory alkalosis is a more long-standing condition. For every 10 mmHg drop in PCO2 in arterial blood, there is a corresponding 5 mEq/L drop in bicarbonate ion. The drop of 5 mEq/L of bicarbonate ion is a compensation effect which reduces the alkalosis effect of the drop in PCO2 in blood. This is termed metabolic compensation. [edit] Mechanism

Respiratory alkalosis generally occurs when some stimulus (see "Causes" below) makes a person hyperventilate. The increased breathing produces increased alveolar respiration, expelling CO2 from the circulation. This alters the dynamic chemical equilibrium of carbon dioxide in the circulatory system, and the system reacts according to Le Chatelier's principle. Circulating hydrogen ions and bicarbonate are shifted through the carbonic acid (H2CO3) intermediate to make more CO2 via the enzyme carbonic anhydrase according to the following reaction:

The net result of this is decreased circulating hydrogen ion concentration, and thus increased pH (alkalosis). There is also a decrease in ionized blood calcium concentration. [edit] Causes

Respiratory alkalosis may be produced accidentally (iatrogenically) during excessive mechanical ventilation. Other causes include: psychiatric causes: anxiety, hysteria and stress CNS causes: stroke, subarachnoid haemorrhage, meningitis drug use: doxapram, aspirin, caffeine and coffee abuse moving into high altitude areas, where the low atmospheric pressure of oxygen stimulates increased ventilation

lung disease such as pneumonia, where a hypoxic drive governs breathing more than CO2 levels (the normal determinant) fever, which stimulates the respiratory centre in the brainstem pregnancy high levels of NH4+ leading to brain swelling and decreased blood flow to the brain [edit] Symptoms

Symptoms of respiratory alkalosis are related to the decreased blood carbon dioxide levels, and include peripheral paraesthesiae. In addition, the alkalosis may disrupt calcium ion balance, and cause the symptoms of hypocalcaemia (such as tetany and fainting) with no fall in total serum calcium levels. [edit] In popular culture

In The Andromeda Strain, Michael Crichton's first novel, only two people exposed to a pathogenic extraterrestrial microbe survive. Scientists investigating these survivors discover that each had abnormal blood pH. One, a baby, had respiratory alkalosis due to constant crying; the other, an old man, drinks Sterno. As a result, it becomes clear that the microbe cannot survive outside a narrow pH range.