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  1. 1. Skip navigation Other encyclopedia articles: A B C D E F G H I J K L M N O P Q R S T U V W X Y Z 0-9 Comprehensive metabolic panel A comprehensive metabolic panel is a group of chemical tests performed on the blood MedlinePlus Topics serum (the part of blood that doesn't contain cells). Laboratory Tests These tests include total cholesterol, total protein, and various electrolytes. Electrolytes in the body include sodium, potassium, chlorine, and many others. Read More Electrolytes The rest of the tests measure chemicals that reflect liver and kidney function. How the Test is Performed A blood sample is needed. For information on giving a blood sample from a vein, see venipuncture. How to Prepare for the Test You should not eat or drink for 8 hours before the test. How the Test Will Feel When the needle is inserted to draw blood, some people feel moderate pain, while others feel only a prick or stinging sensation. Afterward, there may be some throbbing. Why the Test is Performed This test helps provide information about your body's metabolism. It give your doctor information about how your kidneys and liver are working, and can be used to evaluate blood sugar, cholesterol, and calcium levels, among other things. Your doctor may order this test during a yearly exam or routine check up. Normal Results  Albumin: 3.9 to 5.0 g/dL  Alkaline phosphatase: 44 to 147 IU/L  ALT (alanine transaminase): 8 to 37 IU/L  AST (aspartate aminotransferase): 10 to 34 IU/L  BUN (blood urea nitrogen): 7 to 20 mg/dL  Calcium - serum: 8.5 to 10.9 mg/dL  Serum chloride: 101 to 111 mmol/L  CO2 (carbon dioxide): 20 to 29 mmol/L  Creatinine: 0.8 to 1.4 mg/dL **  Direct bilirubin: 0.0 to 0.3 mg/dL  Gamma-GT (gamma-glutamyl transpeptidase): 0 to 51 IU/L  Glucose test: 64 to 128 mg/dL  LDH (lactate dehydrogenase): 105 to 333 IU/L  Phosphorus - serum: 2.4 to 4.1 mg/dL
  2. 2.  Potassium test: 3.7 to 5.2 mEq/L  Serum sodium: 136 to 144 mEq/L  Total bilirubin: 0.2 to 1.9 mg/dL  Total cholesterol: 100 to 240 mg/dL  Total protein: 6.3 to 7.9 g/dL  Uric acid: 4.1 to 8.8 mg/dL **Note: Normal or “healthy” values for creatinine can vary with age. Normal value ranges for all tests may vary slightly among different laboratories. Talk to your doctor about the meaning of your specific test results. Key to abbreviations:  IU = international unit  L = liter  dL = deciliter = 0.1 liter  g/dL = gram per deciliter  mg = milligram  mmol = millimole  mEq = milliequivalents What Abnormal Results Mean Abnormal results can be due to a variety of different medical conditions, including kidney failure, breathing problems, and diabetes-related complications. See the individual tests listed in the normal values section for detailed information. Risks There is very little risk involved with having your blood taken. Veins and arteries vary in size from one patient to another and from one side of the body to the other. Taking blood from some people may be more difficult than from others. Other risks associated with having blood drawn are slight but may include:  Excessive bleeding  Fainting or feeling light-headed  Hematoma (blood accumulating under the skin)  Infection (a slight risk any time the skin is broken) Alternative Names Metabolic panel - comprehensive; Chem-20; SMA20; Sequential multi-channel analysis with computer-20; SMAC20; Metabolic panel 20 Update Date: 2/23/2009 Updated by: David C. Dugdale, III, MD, Professor of Medicine, Division of General Medicine, Department of Medicine, University of Washington School of Medicine. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc. A.D.A.M., Inc. is accredited by URAC, also known as the American Accreditation HealthCare Commission (www.urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. follows rigorous standards of quality and accountability. A.D.A.M. is among the first to achieve this important distinction for online health information and services. Learn more about A.D.A.M.'s editorial policy, editorial process and privacy policy. A.D.A.M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health on the Net Foundation (www.hon.ch). The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. A licensed physician should be consulted for diagnosis and treatment of any and all medical conditions. Call 911 for all medical emergencies. Links to other sites are provided for information only -- they do not constitute endorsements of those other sites. Copyright 1997-2009, A.D.A.M., Inc. Any duplication or distribution of the information contained herein is strictly prohibited.
  3. 3. Skip navigation Other encyclopedia articles: A B C D E F G H I J K L M N O P Q R S T U V W X Y Z 0-9 BUN BUN stands for blood urea nitrogen. Urea nitrogen is what forms when protein breaks MedlinePlus Topics down. Kidney Diseases A test can be done to measure the amount of urea nitrogen in the blood. Read More How the Test is Performed Acute bilateral obstructive uropathy Acute kidney failure Acute tubular necrosis Blood is typically drawn from a vein, usually from the inside of the elbow or the back of Amino acids the hand. The site is cleaned with germ-killing medicine (antiseptic). The health care Ammonium ion provider wraps an elastic band around the upper arm to apply pressure to the area and Gastrointestinal bleeding make the vein swell with blood. Glomerulonephritis Heart attack Next, the health care provider gently inserts a needle into the vein. The blood collects Heart failure into an airtight vial or tube attached to the needle. The elastic band is removed from your Hypovolemic shock arm. Kidney disease Metabolism Once the blood has been collected, the needle is removed, and the puncture site is Renal covered to stop any bleeding. Shock In infants or young children, a sharp tool called a lancet may be used to puncture the skin and make it bleed. The blood collects into a small glass tube called a pipette, or onto a slide or test strip. A bandage may be placed over the area if there is any bleeding. How to Prepare for the Test Many drugs affect BUN levels. Before having this test, make sure the health care provider knows which medications you are taking. Drugs that can increase BUN measurements include:  Allopurinol  Aminoglycosides  Amphotericin B  Aspirin (high doses)  Bacitracin  Carbamazepine  Cephalosporins  Chloral hydrate  Cisplatin  Colistin  Furosemide  Gentamicin  Guanethidine  Indomethacin  Methicillin  Methotrexate  Methyldopa
  4. 4.  Neomycin  Penicillamine  Polymyxin B  Probenecid  Propranolol  Rifampin  Spironolactone  Tetracyclines  Thiazide diuretics  Triamterene  Vancomycin Drugs that can decrease BUN measurements include:  Chloramphenicol  Streptomycin How the Test Will Feel When the needle is inserted to draw blood, some people feel moderate pain, while others feel only a prick or stinging sensation. Afterward, there may be some throbbing. Why the Test is Performed The BUN test is often done to check kidney function. Normal Results 7 - 20 mg/dL. Note that normal values may vary among different laboratories. What Abnormal Results Mean Higher-than-normal levels may be due to:  Congestive heart failure  Excessive protein levels in the gastrointestinal tract  Gastrointestinal bleeding  Hypovolemia  Heart attack  Kidney disease, including glomerulonephritis, pyelonephritis, and acute tubular necrosis  Kidney failure  Shock  Urinary tract obstruction Lower-than-normal levels may be due to:  Liver failure  Low protein diet  Malnutrition  Over-hydration Additional conditions under which the test may be done include:  Acute nephritic syndrome  Alport syndrome  Atheroembolic kidney disease  Dementia due to metabolic causes
  5. 5.  Diabetic nephropathy/sclerosis  Digitalis toxicity  Epilepsy  Generalized tonic-clonic seizure  Goodpasture syndrome  Hemolytic-uremic syndrome (HUS)  Hepatokidney syndrome  Interstitial nephritis  Lupus nephritis  Malignant hypertension (arteriolar nephrosclerosis)  Medullary cystic kidney disease  Membranoproliferative GN I  Membranoproliferative GN II  Type 2 diabetes  Prerenal azotemia  Primary amyloidosis  Secondary systemic amyloidosis  Wilms' tumor Risks Veins and arteries vary in size from one patient to another and from one side of the body to the other. Obtaining a blood sample from some people may be more difficult than from others. Other risks are slight but may include:  Excessive bleeding  Fainting or feeling light-headed  Hematoma (blood accumulating under the skin)  Infection (a slight risk any time the skin is broken) Considerations For people with liver disease, the BUN level may be low even if the kidneys are normal. Alternative Names Blood urea nitrogen References Molitoris BA. Acute kidney injury. In: Goldman L, Ausiello D, eds. Cecil Medicine. 23rd ed. Philadelphia, Pa: Saunders Elsevier; 2007:chap 121. Update Date: 5/13/2009 Updated by: David C. Dugdale, III, MD, Professor of Medicine, Division of General Medicine, Department of Medicine, University of Washington School of Medicine; Jatin M. Vyas, MD, PhD, Assistant Professor in Medicine, Harvard Medical School, Assistant in Medicine, Division of Infectious Disease, Department of Medicine, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc. A.D.A.M., Inc. is accredited by URAC, also known as the American Accreditation HealthCare Commission (www.urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. follows rigorous standards of quality and accountability. A.D.A.M. is among the first to achieve this important distinction for online health information and services. Learn more about A.D.A.M.'s editorial policy, editorial process and privacy policy. A.D.A.M. is also a founding
  6. 6. 07. Creatinine    Primary function of kidney : excrete unwanted materials,                                               retain those chemicals necessary for proper function       1. passive excretion (glomerular filtration)       2. reabsorption from the tubule back into the circulation       3. secretion from the circulation into the tubule    Excretion capacity°¡ kidney function Æò°¡¿¡ ÁÖ ¿äÀÎ.    ExcretionÀº ȯÀÚÀÇ (blood stream> administered substanceÀÇ) renal clearance Æò°¡·Î  ÀÌ·ç¾îÁú ¼ö ÀÖÀ½.      skeletal muscle¿¡¼     creatine phosphate --------> creatinine + H2PO4- + H+     creatine --------> creatinine + H2O (plasma·Î constantÇÏ°Ô release)         --------> glomerular filtrate¿¡ Á¸Àç (tubular reabsorptionÀÌ °ÅÀÇ ¾ø´Ù)     glomerular filtration rate(GFR)°¡ °¨¼ÒÇϸé Ã¼¿Ü·Î excretion ÀÌ °¨¼ÒµÇ°í serum³» ³óµµ°¡ ³ô¾ÆÁü.      -----> renal glomerular functionÀÇ ÁöÇ¥.     creatinineÀÇ outputÀº total body mass º¸´Ù´Â muscle mass¿¡ ´õ ÀÇÁ¸     1) Assay method      Jaffe reaction                                             OH -(0.1 M NaOH)      creatinine + picrate ------------------> red colored complex(A 520 nm) ±¸Á¶´Â ¸ð¸§          i) sample Áß¿¡¼ protein Á¦°Å (proteinÀÌ picrate¿Í ¹ÝÀÀ)         ii) constant Temp.À¯Áö : 30 C ÀÌÇϷΠÀ¯Áö, ÀÌ»óÀÏ °æ¿ì ´Ù¸¥ compound°¡ picrate¿Í ¹ÝÀÀ          iii) time is a significance factor : incubation timeÀ» ´Ã¸®¸é nonspecific colored products°¡ ´Ã¾î³²     ÀÌ·¯ÇÑ interference¸¦ ÁÙÀ̱â À§ÇØ enzyme method°¡ ½Ãµµ Áß      creatinine iminohydrolase¿¡ ÀÇÇØ ammonium ionÀÌ µÇ¾î  colorimetry ¶Ç´Â ion-selective electrode »ç¿ë.      specimen : serum, plasma, urine(1:200 dilution ÇÊ¿ä)     2) Clinical significance     * serum ³» creatinine Áõ°¡ : renal damage 
  7. 7.   creatinine °¨¼Ò : no significance       0.9-1.5 mg/dL (men) > 0.7-1.3 mg/dL (women)         serum creatinine ÃøÁ¤ÈÄ ÇÊ¿ä½Ã         Creatinine clearance : renal functionÀ» assayÇϴµ¥ sensitiveÇÑ ¹æ¹ý.                       glomerular filtration rate(GFR)¸¦ ÃøÁ¤                       24 hrÀÇ urine °ú blood sample Ã¤Ãë                                         UV         1.73                    creatinine clearance(ml/min) = -----  X  -----                                                                       P             S U : urinary creatinine (mg/L)     V : volume of urine (ml/min) P : plasma creatinine (mg/L)     S : surface area of patient 1.73 : standard 70 kgÀÇ surface area¸¦ 1.73  Reference range : 95-140 ml/min (man),                              90-130 ml/min (woman)  creatinine clearance Áõ°¡ : no significance creatinine clearance °¨¼Ò : glomerular filtration rateÀÇ ÀúÇÏ 
  8. 8. Blood sugar From Wikipedia, the free encyclopedia Blood sugar concentration, or glucose level, refers to the  amount of glucose present in the blood of a human or  animal. Normally, in mammals the blood glucose level is  maintained at a reference range between about 3.6 and 5.8  mM (mmol/l). It is tightly regulated as a part of metabolic  homeostasis. Mean normal blood glucose levels in humans are about  90 mg/dl, equivalent to 5mM (mmol/l) (since the molecular  weight of glucose, C6H12O6, is about 180 g/mol). The total  amount of glucose normally in circulating human blood is  therefore about 3.3 to 7g (assuming an ordinary adult blood  volume of 5 litres, plausible for an average adult male).  Glucose levels rise after meals for an hour or two by a few  grams and are usually lowest in the morning, before the  first meal of the day. Transported via the bloodstream from  the intestines or liver to body cells, glucose is the primary  source of energy for body's cells, fats and oils (ie, lipids) The fluctuation of blood sugar (red) and the sugar-lowering hormone  being primarily a compact energy store. insulin (blue) in humans during the course of a day with three meals.  One of the effects of a sugar-rich vs a starch-rich meal is highlighted. Failure to maintain blood glucose in the normal range leads  to conditions of persistently high (hyperglycemia) or low (hypoglycemia) blood sugar. Diabetes mellitus, characterized by  persistent hyperglycemia from any of several causes, is the most prominent disease related to failure of blood sugar regulation. Contents  1 Normal values  2 Regulation  3 Glucose measurement  3.1 Sample type  3.2 Measurement techniques  3.3 Blood glucose laboratory tests  3.4 Clinical correlation  4 Health effects  5 Low blood sugar  6 Converting glucose units  7 Comparative content  8 Etymology and use of term  9 Blood glucose in birds and reptiles  10 References  11 See also Normal values Despite widely variable intervals between meals or the occasional consumption of meals with a substantial carbohydrate load,  human blood glucose levels normally remain within a remarkably narrow range. In most humans this varies from about  82 mg/dl to perhaps 110 mg/dl (4.4 to 6.1 mmol/l) except shortly after eating when the blood glucose level rises temporarily up  to maybe 140 mg/dl (7.8 mmol/l) or a bit more in non-diabetics. The American Diabetes Association recommends a post-meal  glucose level less than 180 mg/dl (10 mmol/l) and a pre-meal plasma glucose of 90-130 mg/dl (5 to 7.2 mmol/l). [1] It is usually a surprise to realize how little glucose is actually maintained in the blood and body fluids. The control mechanism  works on very small quantities. In a healthy adult male of 75 kg (165 lb) with a blood volume of 5 litres (1.3 gal), a blood 
  9. 9. glucose level of 100 mg/dl or 5.5 mmol/l corresponds to about 5 g (0.2 oz or 0.002 gal, 1/500 of the total) of glucose in the  blood and approximately 45 g (1½ ounces) in the total body water (which obviously includes more than merely blood and will  be usually about 60% of the total body weight in men). A more familiar comparison may help – 5 grams of glucose is about  equivalent to a small sugar packet as provided in many restaurants with coffee or tea, with people using typically 1 to 3 packets  per cup. Regulation Main article: Blood sugar regulation The homeostatic mechanism which keeps the blood value of glucose in a remarkably narrow range is composed of several  interacting systems, of which hormone regulation is the most important. There are two types of mutually antagonistic metabolic hormones affecting blood glucose levels:  catabolic hormones (such as glucagon, growth hormone, cortisol and catecholamines) which increase blood glucose;   and one anabolic hormone (insulin), which decreases blood glucose. Glucose measurement Main article: Blood glucose monitoring Sample type Glucose can be measured in whole blood or serum (ie, plasma). Historically, blood glucose values were given in terms of  whole blood, but most laboratories now measure and report the serum glucose levels. Because red blood cells (erythrocytes)  have a higher concentration of protein (eg, hemoglobin) than serum, serum has a higher water content and consequently more  dissolved glucose than does whole blood. To convert from whole-blood glucose, multiplication by 1.15 has been shown to  generally give the serum/plasma level. Collection of blood in clot tubes for serum chemistry analysis permits the metabolism of glucose in the sample by blood cells  until separated by centrifugation. Red blood cells, for instance, do not require insulin to intake glucose from the blood. Higher  than normal amounts of white or red blood cell counts can lead to excessive glycolysis in the sample with substantial reduction  of glucose level if the sample is not processed quickly. Ambient temperature at which the blood sample is kept prior to  centrifuging and separation of plasma/serum also affects glucose levels. At refrigerator temperatures, glucose remains  relatively stable for several hours in a blood sample. At room temperature (25 °C), a loss of 1 to 2% of total glucose per hour  should be expected in whole blood samples. Loss of glucose under these conditions can be prevented by using Fluoride tubes  (ie, gray-top) since fluoride inhibits glycolysis. However, these should only be used when blood will be transported from one  hospital laboratory to another for glucose measurement. Red-top serum separator tubes also preserve glucose in samples after  being centrifuged isolating the serum from cells. Particular care should be given to drawing blood samples from the arm opposite the one in which an intravenous line is  inserted, to prevent contamination of the sample with intravenous fluids. Alternatively, blood can be drawn from the same arm  with an IV line after the IV has been turned off for at least 5 minutes, and the arm elevated to drain infused fluids away from  the vein. Inattention can lead to large errors, since as little as 10% contamination with 5% dextrose (D5W) will elevate glucose  in a sample by 500 mg/dl or more. Remember that the actual concentration of glucose in blood is very low, even in the hyperglycemic. Arterial, capillary and venous blood have comparable glucose levels in a fasting individual. After meals venous levels are  somewhat lower than capillary or arterial blood; a common estimate is about 10%. Measurement techniques Two major methods have been used to measure glucose. The first, still in use in some places, is a chemical method exploiting  the nonspecific reducing property of glucose in a reaction with an indicator substance that changes color when reduced. Since  other blood compounds also have reducing properties (e.g., urea, which can be abnormally high in uremic patients), this  technique can produce erroneous readings in some situations (5 to 15 mg/dl has been reported). The more recent technique,  using enzymes specific to glucose, are less susceptible to this kind of error. The two most common employed enzymes are 
  10. 10. glucose oxidase and hexokinase. In either case, the chemical system is commonly contained on a test strip, to which a blood sample is applied, and which is  then inserted into the meter for reading. Test strip shapes and their exact chemical composition vary between meter systems  and cannot be interchanged. Formerly, some test strips were read (after timing and wiping away the blood sample) by visual  comparison against a color chart printed on the vial label. Strips of this type are still used for urine glucose readings, but for  blood glucose levels they are obsolete. Their error rates were, in any case, much higher. Urine glucose readings, however taken, are much less useful. In properly functioning kidneys, glucose does not appear in urine  until the renal threshold for glucose has been exceeded. This is substantially above any normal glucose level, and so is  evidence of an existing severe hyperglycemic condition. However, urine is stored in the bladder and so any glucose in it might  have been produced at any time since the last time the bladder was emptied. Since metabolic conditions change rapidly, as a  result of any of several factors, this is delayed news and gives no warning of a developing condition. Blood glucose monitoring  is far preferable, both clinically and for home monitoring by patients. I. CHEMICAL METHODS A. Oxidation-Reduction Reaction 1. Alkaline Copper Reduction Folin Wu Blue end- Method product Benedict's   Modification of Folin wu for Qualitative Urine Glucose  method Nelson Somoygi  Blue end- Method product Yellow- Neocuproine  * orange color  Method Neocuproine Shaeffer   Utilizes the principle of Iodine reaction with Cuprous byproduct.  Hartmann   Excess I2 is then titrated with thiosulfate. Somygi 2. Alkaline Ferricyanide Reduction Colorless  end product;  other  Hagedorn  reducing  Jensen substances interfere  with  reaction B. Condensation  Utilizes aromatic amines and hot acetic acid Ortho-toluidine   Forms Glycosylamine and Schiff's base which is emerald green in color  Method  This is the most specific method, but the reagent used is toxic  Anthrone  (Phenols)   Forms hydroxymethyl furfural in hot acetic acid  Method II. ENZYMATIC METHODS A. Glucose Oxidase Inhibited by 
  11. 11. reducing  substances  Saifer  like BUA,  Gernstenfield  Bilirubin,  Method Glutathione,  Ascorbic Acid  uses 4-aminophenazone oxidatively coupled with Phenol Trinder Method  Subject to less interference by increases serum levels of Creatinine, Uric Acid or Hemoglobin  Inhibited by Catalase  A Dry Chemistry Method  Kodak   Uses Reflectance Spectrophotometry to measure the intensity of color through a lower transparent  Ektachem film   Home monitoring blood glucose assay method  Glucometer  Uses a strip impregnated with a Glucose Oxidase reagent B. Hexokinase  NADP as cofactor   NADPH (reduced product) is measured in 340 nm   More specific than Glucose Oxidase method due to G-6PO_4, which inhibits interfering substances except when  sample is hemolyzed  Blood glucose laboratory tests 1. fasting blood sugar (ie, glucose) test (FBS)  2. urine glucose test  3. two-hr postprandial blood sugar test (2-h PPBS)  4. oral glucose tolerance test (OGTT) 5. intravenous glucose tolerance test (IVGTT)  6. glycosylated hemoglobin (HbA1C)  7. self-monitoring of glucose level via patient testing Clinical correlation The fasting blood glucose (FBG) level is the most commonly used indication of overall glucose homeostasis, largely because disturbing events such as food intake are avoided. Conditions affecting glucose levels are shown in the table below.  Abnormalities in these test results are due to problems in the multiple control mechanism of glucose regulation. The metabolic response to a carbohydrate challenge is conveniently assessed by a postprandial glucose level drawn 2 hours  after a meal or a glucose load. In addition, the glucose tolerance test, consisting of several timed measurements after a  standardized amount of oral glucose intake, is used to aid in the diagnosis of diabetes. It is regarded as the gold standard of clinical tests of the insulin / glucose control system, but is difficult to administer, requiring much time and repeated blood tests.  Note that food commonly includes carbohydrates which don't participate in the metabolic control system; simple sugars such  as fructose, many of the disaccarhides (which either contain simple sugars other than glucose or cannot be digested by humans)  and the more complex sugars which also cannot be digested by humans. And there are carbohydrates which are not digested  even with the assistance of gut bacteria; several of the fibres (soluble or insoluble) are chemically carbohydrates. Food also  commonly contains components which affect glucose (and other sugar's) digestion; fat, for example slows down digestive  processing, even for such easily handled food constituents as starch. Avoiding the effects of food on blood glucose  measurement is important for reliable results since those effects are so variable.
  12. 12. Error rates for blood glucose measurements systems vary, depending on laboratories, and on the methods used. Colorimetry  techniques can be biased by color changes in test strips (from airborne or finger borne contamination, perhaps) or interference  (eg, tinting contaminants) with light source or the light sensor. Electrical techniques are less susceptible to these errors, though  not to others. In home use, the most important issue is not accuracy, but trend. Thus if your meter / test strip system is  consistently wrong by 10%, there will be little consequence, as long as changes (eg, due to exercise or medication adjustments)  are properly tracked. In the US, home use blood test meters must be approved by the Federal Food and Drug Administration  before they can be sold. Similar supervision is imposed in other jurisdictions. Finally, there are several influences on blood glucose level aside from food intake. Infection, for instance, tends to change  blood glucose levels, as does stress either physical or psychological. Exercise, especially if prolonged or long after the most recent meal, will have an effect as well. In the normal person, maintenance of blood glucose at near constant levels will  nevertheless be quite effective. Causes of Abnormal Glucose Levels Persistent Hyperglycemia Transient Hyperglycemia Persistent Hypoglycemia Transient Hypoglycemia Reference Range, FBG: 70-110 mg/dl Diabetes Mellitus Pheochromocytoma Insulinoma Acute Alcohol Ingestion Adrenal cortical hyperactivity  Adrenal cortical insufficiency  Drugs: salicylates, Severe Liver Disease Cushing's Syndrome Addison's Disease antituberculosis agents Hyperthyroidism Acute stress reaction Hypopituitarism Severe Liver disease Several Glycogen storage Acromegaly Shock Galactosemia diseases Ectopic Insulin production  Hereditary fructose  Obesity Convulsions from tumors intolerance Health effects If blood sugar levels drop too low, a potentially fatal condition called hypoglycemia develops. Symptoms may include  lethargy, impaired mental functioning, irritability, shaking, weakness in arm and leg muscles, sweatting and loss of  consciousness. Brain damage is even possible. If levels remain too high, appetite is suppressed over the short term. Long-term hyperglycemia causes many of the long-term  health problems associated with diabetes, including eye, kidney, heart disease and nerve damage. Low blood sugar Some people report drowsiness or impaired cognitive function several hours after meals, which they believe is related to a drop  in blood sugar, or "low blood sugar". For more information, see:  idiopathic postprandial syndrome  hypoglycemia Mechanisms which restore satisfactory blood glucose levels after hypoglycemia must be quick and effective, because of the  immediately serious consequences of insufficient glucose; in the extreme, coma, but also less immediately dangerous,  confusion or unsteadiness, amongst many other symptoms. This is because, at least in the short term, it is far more dangerous  to have too little glucose in the blood than too much. In healthy individuals these mechanisms are generally quite effective, and  symptomatic hypoglycemia is generally only found in diabetics using insulin or other pharmacological treatment. Such  hypoglycemic episodes vary greatly between persons and from time to time, both in severity and swiftness of onset. For severe  cases, prompt medical assistance is essential, as damage (to brain and other tissues) and even death will result from sufficiently  low blood glucose levels. Converting glucose units In most countries, blood glucose is reported in terms of molarity, measured in mmol/L (or millimolar, abbreviated mM). In the 
  13. 13. United States, and to a lesser extent elsewhere, mass concentration, measured in mg/dL, is typically used. To convert blood glucose readings between the two units:  Divide a mg/dL figure by 18 (or multiply by 0.055) to get mmol/L.   Multiply a mmol/L figure by 18 (or divide by 0.055) to get mg/dL.  Comparative content Reference ranges for blood tests, comparing blood content of glucose (shown in darker green)  with other constituents. Etymology and use of term The term 'blood sugar' has colloquial origins. In a physiological context, the term is a misnomer because it refers to glucose,  yet other sugars besides glucose are always present. Food contains several different types (eg, fructose (largely from  fruits/table sugar/industrial sweeteners). galactose (milk and dairy products), as well as several food additives such as sorbitol,  xylose, maltose, ...). But because these other sugars are largely inert with regard to the metabolic control system (ie, that  controlled by insulin secretion), since glucose is the dominant controlling signal for metabolic regulation, the term has gained  currency, and is used by medical staff and lay folk alike. The table above reflects some of the more technical and closely  defined terms used in the medical field. Blood glucose in birds and reptiles In birds and reptiles the processing of sugars is done differently, the pancreas is slightly more well developed in birds than in  mammals, perhaps as a partial compensation for the lack of saliva and chewing. It produces carbohydrate, fat and protein  digesting enzymes which are secreted into the small intestine. The liver has two distinct lobes each with its own duct leading  into the small intestine. The liver, as in mammals, houses the bile, which in birds however is acidic and not alkaline as it is in  mammals. Many birds do not have a gall bladder to hold the bile, and it is secreted directly into the pancreatic ducts. References 1. ^ American Diabetes Association. January 2006 Diabetes Care. "Standards of Medical Care-Table 6 and Table 7, Correlation between  A1C level and Mean Plasma Glucose Levels on Multiple Testing over 2-3 months." Vol. 29 Supplement 1 Pages 51-580.   John Bernard Henry, M.D.: Clinical diagnosis and Management by Laboratory Methods 20th edition, Saunders,  Philadelphia, PA, 2001.   Ronald A. Sacher and Richard A. McPherson: Widmann's Clinical Interpretation of Laboratory Tests 11th edition, F.A.  Davis Company, 2001.  See also  Current research - Boronic acids in supramolecular chemistry: Saccharide recognition  Blood glucose monitoring Retrieved from "http://en.wikipedia.org/wiki/Blood_sugar" Categories: Human homeostasis | Blood tests | Diabetes  This page was last modified on 7 December 2009 at 16:52.   Text is available under the Creative Commons Attribution-ShareAlike License; additional terms may apply. See Terms  of Use for details.
  14. 14. Wikipedia® is a registered trademark of the Wikimedia Foundation, Inc., a non-profit organization.  Contact us
  15. 15. Web Images Videos Shopping News Maps More MSN Hotmail Sign in | United States | Preferences Blood sugar Blood sugar Make Bing your decision engine Bing Normal values Reference ranges for blood tests Regulation overview outline images locations Glucose measurement ALL RESULTS REFERENCE » WIKIPEDIA ARTICLES Submit Query Sample type Search this article highlighter Reference Measurement techniques Blood sugar Blood glucose laboratory tests Clinical correlation For the song by Pendulum, see Blood Sugar / Axle Grinder. Health effects Blood sugar concentration, or glucose level, refers to Low blood sugar the amount of glucose present in the blood of a human or Converting glucose units animal. Normally, in mammals the blood glucose level is Comparative content maintained at a reference range between about 3.6 and Etymology and use of term 5.8 mM (mmol/l). It is tightly regulated as a part of Blood glucose in birds and metabolic homeostasis. reptiles Mean normal blood glucose levels in humans are about 90 References mg/dl, equivalent to 5mM (mmol/l) (since the molecular See also weight of glucose, C6H12O6, is about 180 g/mol). The total amount of glucose normally in circulating human blood is 1 therefore about 3.3 to 7g (assuming an ordinary adult ... Locations v... blood volume of 5 litres, plausible for an average adult male). Glucose levels rise after meals for an hour or two by a few grams and are usually lowest in the morning, before the first meal of the day. Transported via the bloodstream from the intestines or liver to body cells, glucose is the primary source of energy for body's cells, The fluctuation of blood sugar (red) and the sugar-lowering hormone fats and oils (ie, lipids) being primarily a compact energy insulin (blue) in humans during the course of a day with three meals. One of the effects of a sugar-rich vs a starch-rich meal is highlighted. store. Failure to maintain blood glucose in the normal range leads to conditions of persistently high (hyperglycemia) or low (hypoglycemia) Images Videos blood sugar. Diabetes mellitus, characterized by persistent hyperglycemia from any of several causes, is the most prominent disease related to failure of blood sugar regulation. Normal values view all 24 view all 15 Despite widely variable intervals between meals or the occasional consumption of meals with a substantial carbohydrate load, human blood glucose levels normally remain within a remarkably narrow range. In most humans this varies from about 80 mg/dl to perhaps 110 mg/dl (4.4 to 6.1 mmol/l) except shortly after eating when the blood glucose level rises temporarily up to maybe 140 mg/dl (7.8 mmol/l) or a bit more in non-diabetics. The American Diabetes Association recommends a post-meal glucose level less than 180 mg/dl (10 mmol/l) and a pre-meal plasma glucose of 90-130 mg/dl (5 to 7.2 mmol/l). [1] It is usually a surprise to realize how little glucose is actually maintained in the blood and body fluids. The control mechanism works on very small quantities. In a healthy adult male of 75 kg (165 lb) with a blood volume of 5 litres (1.3 gal), a blood glucose level of 100 mg/dl or 5.5 mmol/l corresponds to about 5 g (0.2 oz or 0.002 gal, 1/500 of the total) of glucose in the blood and approximately 45 g (1½ ounces) in the total body water (which obviously includes more than merely blood and will be usually about 60% of the total body weight in men). A more familiar comparison may help – 5 grams of glucose is about equivalent to a small sugar packet as provided in many restaurants with coffee or tea, with people using typically 1 to 3 packets per cup. Regulation Main article: Blood sugar regulation The homeostatic mechanism which keeps the blood value of glucose in a remarkably narrow range is composed of several interacting systems, of which hormone regulation is the most important. There are two types of mutually antagonistic metabolic hormones affecting blood glucose levels:  catabolic hormones (such as glucagon, growth hormone, cortisol and catecholamines) which increase blood glucose;  and one anabolic hormone (insulin), which decreases blood glucose. Glucose measurement Main article: Blood glucose monitoring Sample type Glucose can be measured in whole blood, serum (ie, plasma). Historically, blood glucose values were given in terms of whole blood, but most laboratories now measure and report the serum glucose levels. Because red blood cells (erythrocytes) have a higher concentration of protein (eg, hemoglobin) than serum, serum has a higher water content and consequently more dissolved glucose than does whole blood. To convert from whole-blood glucose, multiplication by 1.15 has been shown to generally give the serum/plasma level. Collection of blood in clot tubes for serum chemistry analysis permits the metabolism of glucose in the sample by blood cells until separated by centrifugation. Red blood cells, for instance, do not require insulin to intake glucose from the blood. Higher than normal amounts of white or red blood cell counts can lead to excessive glycolysis in the sample with substantial reduction of glucose level if the sample is not processed quickly. Ambient temperature at which the blood sample is kept prior to centrifuging and separation of plasma/serum also affects glucose levels. At refrigerator temperatures, glucose remains relatively stable for several hours in a blood sample. At room temperature (25 °C), a loss of 1 to 2% of total glucose per hour should be expected in whole blood samples. Loss of glucose under these conditions can be prevented by using Fluoride tubes (ie, gray-top) since fluoride inhibits glycolysis. However, these should only be used when blood will be transported from one hospital laboratory to another for glucose measurement. Red-top serum separator tubes also preserve glucose in samples after being centrifuged isolating the serum from cells. Particular care should be given to drawing blood samples from the arm opposite the one in which an intravenous line is inserted, to prevent contamination of the sample with intravenous fluids. Alternatively, blood can be drawn from the same arm with an IV line after the IV has been turned off for at least 5 minutes, and the arm elevated to drain infused fluids away from the vein. Inattention can lead to large errors, since as little as 10% contamination with 5% dextrose (D5W) will elevate glucose in a sample by 500 mg/dl or more. Remember that the actual concentration of glucose in blood is very low, even in the hyperglycemic. Arterial, capillary and venous blood have comparable glucose levels in a fasting individual. After meals venous levels are somewhat lower than capillary or arterial blood; a common estimate is about 10%. Measurement techniques Two major methods have been used to measure glucose. The first, still in use in some places, is a chemical method exploiting the
  16. 16. Blood sugar Normal values Regulation overview outline images locations Glucose measurement Sample type highlighter Measurement techniques Blood glucose laboratory tests Clinical correlation Health effects Low blood sugar Converting glucose units Comparative content Etymology and use of term Blood glucose in birds and reptiles References See also 1 Locations ... ... v... all Images Videos view all 24 view all 15
  17. 17. Blood sugar Normal values Regulation overview outline images locations Glucose measurement Sample type highlighter Measurement techniques Blood glucose laboratory tests Clinical correlation Health effects Low blood sugar Converting glucose units Comparative content Etymology and use of term Blood glucose in birds and reptiles References See also 1 Locations ... ... v... all Images Videos view all 24 view all 15
  18. 18. Blood sugar Normal values Regulation overview outline images locations Glucose measurement Sample type highlighter Measurement techniques Blood glucose laboratory tests Clinical correlation Health effects Low blood sugar Converting glucose units Comparative content Etymology and use of term Blood glucose in birds and reptiles References See also 1 Locations ... ... v... all Images Videos view all 24 view all 15
  19. 19. Oliguria A cardinal sign of renal and urinary tract disorders, oliguria is clinically defined as urine output of less than 400 ml/24 hours. Typically, this sign occurs abruptly and may herald  serious—possibly life-threatening—hemodynamic instability. Its causes can be classified as prerenal (decreased renal blood flow), intrarenal (intrinsic renal damage), or  postrenal (urinary tract obstruction); the pathophysiology differs for each classification. (See How oliguria develops, pages 442 and 443.) Oliguria associated with a prerenal or  postrenal cause is usually promptly reversible with treatment, although it may lead to intrarenal damage if untreated. However, oliguria associated with an intrarenal cause is  usually more persistent and may be irreversible. History and physical examination Begin by asking the patient about his usual daily voiding pattern, including frequency and amount. When did he first notice changes in this pattern and in the color, odor, or  consistency of his urine? Ask about pain or burning on urination. Has the patient had a fever? Note his normal daily fluid intake. Has he recently been drinking more or less than  usual? Has his intake of caffeine or alcohol changed drastically? Has he had recent episodes of diarrhea or vomiting that might cause fluid loss? Next, explore associated  complaints, especially fatigue, loss of appetite, thirst, dyspnea, chest pain, or recent weight gain or loss (in dehydration). Check for a history of renal, urinary tract, or cardiovascular disorders. Note recent traumatic injury or surgery associated with significant blood loss as well as recent blood  transfusions. Was the patient exposed to nephrotoxic agents, such as heavy metals, organic solvents, anesthetics, or radiographic contrast media? Next, obtain a drug history.  Begin the physical examination by taking the patient's vital signs and weighing him. Assess his overall appearance for edema. Palpate both kidneys for tenderness and  enlargement, and percuss for costovertebral angle (CVA) tenderness. Also, inspect the flank area for edema or erythema. Auscultate the heart and lungs for abnormal sounds  and the flank area for renal artery bruits. Assess the patient for edema or signs of dehydration such as dry mucous membranes.  Obtain a urine specimen and inspect it for abnormal color, odor, or sediment. Use reagent strips to test for glucose, protein, and blood. Also, use a urinometer to measure  specific gravity. Medical causes Acute tubular necrosis (ATN).An early sign of ATN, oliguria may occur abruptly (in shock) or gradually (in nephrotoxicity). Usually, it persists for about 2 weeks, followed by  polyuria. Related features include signs of hyperkalemia (muscle weakness and cardiac arrhythmias), uremia (anorexia, confusion, lethargy, twitching, seizures, pruritus, and  Kussmaul's respirations), and heart failure (edema, jugular vein distention, crackles, and dyspnea).  Calculi.Oliguria or anuria may result from calculi lodging in the kidneys, ureters, bladder outlet, or urethra. Associated signs and symptoms include urinary frequency and  urgency, dysuria, and hematuria or pyuria. Usually, the patient experiences renal colic—excruciating pain that radiates from the CVA to the flank, the suprapubic region, and the  external genitalia. This pain may be accompanied by nausea, vomiting, hypoactive bowel sounds, abdominal distention and, occasionally, fever and chills. Cholera. With cholera, severe water and electrolyte loss lead to oliguria, thirst, weakness, muscle cramps, decreased skin turgor, tachycardia, hypotension, and abrupt watery  diarrhea and vomiting. Death may occur in hours without treatment.  Glomerulonephritis (acute).Acute glomerulonephritis produces oliguria or anuria. Other features are a mild fever, fatigue, gross hematuria, proteinuria, generalized edema,  elevated blood pressure, headache, nausea and vomiting, flank and abdominal pain, and signs of pulmonary congestion (dyspnea and a productive cough).  Heart failure.Oliguria may occur with left-sided heart failure as a result of low cardiac output and decreased renal perfusion. Accompanying signs and symptoms include  dyspnea, fatigue, weakness, peripheral edema, jugular vein distention, tachycardia, tachypnea, crackles, and a dry or productive cough. With advanced or chronic heart failure, the patient may also develop orthopnea, cyanosis, clubbing, a ventricular gallop, diastolic hypertension, cardiomegaly, and hemoptysis. Hypovolemia. Any disorder that decreases circulating fluid volume can produce oliguria. Associated findings include orthostatic hypotension, apathy, lethargy, fatigue, gross  muscle weakness, anorexia, nausea, profound thirst, dizziness, sunken eyeballs, poor skin turgor, and dry mucous membranes. Pyelonephritis (acute).Accompanying the sudden onset of oliguria with acute pyelonephritis are a high fever with chills, fatigue, flank pain, CVA tenderness, weakness,  nocturia, dysuria, hematuria, urinary frequency and urgency, and tenesmus. The urine may appear cloudy. Occasionally, the patient also experiences anorexia, diarrhea, and  nausea and vomiting.  Renal failure (chronic).Oliguria is a major sign of end-stage chronic renal failure. Associated findings reflect progressive uremia and include fatigue, weakness, irritability,  uremic fetor, ecchymoses and petechiae, peripheral edema, elevated blood pressure, confusion, emotional lability, drowsiness, coarse muscle twitching, muscle cramps,  peripheral neuropathies, anorexia, a metallic taste in the mouth, nausea and vomiting, constipation or diarrhea, stomatitis, pruritus, pallor, and yellow- or bronze-tinged skin.  Eventually, seizures, coma, and uremic frost may develop.  Renal vein occlusion (bilateral).Bilateral renal vein occlusion occasionally causes oliguria accompanied by acute low back and flank pain, CVA tenderness, fever, pallor, hematuria, enlarged and palpable kidneys, edema and, possibly, signs of uremia. Toxemia of pregnancy.With severe preeclampsia, oliguria may be accompanied by elevated blood pressure, dizziness, diplopia, blurred vision, epigastric pain, nausea and 
  20. 20. vomiting, irritability, and a severe frontal headache. Typically, oliguria is preceded by generalized edema and sudden weight gain of more than 3 lb (1.4 kg) per week during the  second trimester, or more than 1 lb (0.45 kg) per week during the third trimester. If preeclampsia progresses to eclampsia, the patient develops seizures and may slip into coma. Urethral stricture.Urethral stricture produces oliguria accompanied by chronic urethral discharge, urinary frequency and urgency, dysuria, pyuria, and a diminished urine stream.  As the obstruction worsens, urine extravasation may lead to formation of urinomas and urosepsis.  Other causes Diagnostic studies.Radiographic studies that use contrast media may cause nephrotoxicity and oliguria.  Drugs.Oliguria may result from drugs that cause decreased renal perfusion (diuretics), nephrotoxicity (most notably, aminoglycosides and chemotherapeutic drugs), urine  retention (adrenergics and anticholinergics), or urinary obstruction associated with precipitation of urinary crystals (sulfonamides and acyclovir).  Nursing considerations ▪ Monitor the patient's vital signs, intake and output, and daily weight.  ▪ Depending on the cause of oliguria, restrict fluids to between 0.6 and 1 L more than the patient's urine output for the previous day.  ▪ Provide a diet low in sodium, potassium, and protein. ▪ Prepare the patient for diagnostic tests, such as laboratory tests (including serum blood urea nitrogen and creatinine levels, urea and creatinine clearance, urine sodium levels,  and urine osmolality), abdominal X-rays, ultrasonography, a computed tomography scan, cystography, and a renal scan. ▪ Prepare the patient for dialysis.  Patient teaching ▪ Explain any fluid and dietary restrictions.  ▪ Explain the underlying disorder and the treatment plan. Pictures
  21. 21. Book Source Details Book Title: Nursing: Interpreting Signs and Symptoms  Author(s): Springhouse  Year of Publication: 2007  Copyright Details: Nursing: Interpreting Signs and Symptoms, Copyright © 2007 Lippincott Williams & Wilkins.  Other Book Chapters Related to Urinary symptoms Read excerpts from these other book chapters related to Urinary symptoms:  Medical Books Excerpts DYSURIA "Algorithmic Diagnosis of Symptoms and Signs" (2003) ENURESIS "Algorithmic Diagnosis of Symptoms and Signs" (2003) NOCTURIA "Algorithmic Diagnosis of Symptoms and Signs" (2003) POLYURIA "Algorithmic Diagnosis of Symptoms and Signs" (2003) PROTEINURIA "Algorithmic Diagnosis of Symptoms and Signs" (2003) PYURIA "Algorithmic Diagnosis of Symptoms and Signs" (2003) DIFFICULTY URINATING "Algorithmic Diagnosis of Symptoms and Signs" (2003) FREQUENCY OF URINATION "Algorithmic Diagnosis of Symptoms and Signs" (2003) INCONTINENCE OF URINE "Algorithmic Diagnosis of Symptoms and Signs" (2003) URINE COLOR CHANGES "Algorithmic Diagnosis of Symptoms and Signs" (2003) ANURIA OR OLIGURIA "Algorithmic Diagnosis of Symptoms and Signs" (2003) Dysuria "In a Page: Signs and Symptoms" (2004) Polyuria "In a Page: Signs and Symptoms" (2004) Urinary Stream (Decreased) "In a Page: Signs and Symptoms" (2004) Dysuria "In A Page: Pediatric Signs and Symptoms" (2007) Enuresis "In A Page: Pediatric Signs and Symptoms" (2007)
  22. 22. More About Causes of Urinary symptoms Back to symptom: Urinary symptoms: Introduction (review 1071 causes)  Next Book Extract About Urinary symptoms: Polyuria (Nursing: Interpreting Signs and Symptoms) All Book Extracts: All Online Book Extracts for Urinary symptoms More About This Book: Title: Nursing: Interpreting Signs and Symptoms Authors: Springhouse  Publisher: Lippincott Williams & Wilkins Copyright: 2007  ISBN: 1-58255-668-7   » Next page: Polyuria (Nursing: Interpreting Signs and Symptoms) Rate This Website What do you think about the features of this website? Take our user survey and have your say:  Website User Survey Medical Tools & Articles: Next articles: Polyuria (Nursing: Interpreting Signs and Symptoms) Urinary frequency (Nursing: Interpreting Signs and Symptoms) Urinary hesitancy (Nursing: Interpreting Signs and Symptoms) Urinary incontinence (Nursing: Interpreting Signs and Symptoms) Urinary urgency (Nursing: Interpreting Signs and Symptoms) Tools & Services: Bookmark this page Take a survey relating to Urinary symptoms Symptom Search Symptom Checker Medical Dictionary Give your feedback Medical Articles: Disease & Treatments Search Misdiagnosis Center Full list of interesting articles Forums & Message Boards Ask or answer a question at the Boards: I cannot get a diagnosis. Please help. Tell us your medical story. Share your misdiagnosis story. What is the best treatment for my condition? See all the Boards.
  23. 23. Section VI . The Kidneys And The Body Fluids This section was written following fruitful discussions with my colleagues Peter Bie, Niels-Henrik Holstein- Rathlou, Paul Leyssac, Finn Michael Karlsen, and medical students Margrethe Lynggaard and Mads Dalsgaard. The concept flux is net-transport of substance per time unit across an area unit. Flux is equal to concentration multiplied by flow or mol per time unit across a barrier area Frequently used abbreviations in this section are Chapter 24 Chapter 24. Body Fluids and Regulation Body Fluids And Regulation Study Objectives Principles Definitions Study Objectives Essentials • To define the concepts: Dehydration, hyponatraemia, intracellular fluid volume (ICV), Pathophysiology Equations extracellular fluid volume (ECV), interstitial fluid (ISF), overhydration, oxidation water, Self-Assessment radioactivity, specific activity, and total body water. Answers Highlights • To describe the daily water balance, the K+ - and Na+ -balance, sweat secretion, the Further Reading ionic composition in blood plasma, the water content of fat- and muscle- tissue and the Fig. 24-1 daily water transfer across the gastro-intestinal mucosa. To describe the osmotic pressure Fig. 24-2 Fig. 24-3 in the body fluids, the measurement of fluid compartments by indicator dilution, the Fig. 24-4 measurement of total body-K+ and -Na+ and the related dynamic pools. Fig. 24-5 Fig. 24-6 • To draw models of the body fluid compartments. Fig. 24-7 Fig. 24-8 • To explain the influence of age, sex and weight on the size of the total body water and Fig. 24-9 Fig. 24-10 its phases. To explain disorders with increased or reduced extracellular fluid volume and shock. Return to chapter 24 Return to Content • To apply and use the above concepts in problem solving and in case histories. Principles • The law of conservation of matter states that mass or energy can neither be created nor destroyed (the principle of mass balance). The principle is here used to measure physiological fluid compartments and the body content of ions. Definitions • Concentration: The concentration of a solute is the amount of solute in a given fluid volume. • Dehydration is a clinical condition with an abnormal reduction of one or more of the major fluid compartments (ie, total body water with shrinkage of blood volume or ISF). • Dextrans are polysaccharides of high molecular weight. • Intracellular fluid volume (ICV) refers to the volume of fluid inside all cells. This volume normally contains 26-28 litre (l) out of the total 42 l of water in a 70-kg person. - One litre of water equals one kg of water. • Extracellular fluid volume (ECV) refers to the interstitial and the plasma volume. The ECV contains the remaining water (14-16 kg) with most of the water in tissue fluid (ISF) and about 3 kg of water in plasma. - Interstitial fluid (ISF) is the tissue fluid between the cells in the extravascular space. • Hyperkalaemia refers to a clinical condition with plasma-[K+ ] above 5 mM (mmol/l of plasma). +
  24. 24. • Hypokalaemia refers to a clinical condition with plasma-[K ] below 3.5 mM. • Hypernatraemia refers to a clinical condition with plasma-[Na+ ] above 145 mM. • Hyponatraemia refers to a clinical condition with plasma-[Na+ ] below 135 mM. • Oedema refers to a clinical condition with an abnormal accumulation of tissue fluid or interstitial fluid. • Osmolality is a measure of the osmotic active particles in one kg of water. Plasma- osmolality is given in Osmol per kg of water. Water occupies 93-94% of plasma in healthy persons. Plasma osmolality is normally maintained constant by the antidiuretic hormone feedback system. • Overhydration refers to a clinical condition with an abnormal increase in total body water resulting in an increased ECV and thus salt accumulation. • Oxidation water or metabolic water (oxidative phosphorylation) refers to the daily water production by combustion of food - normally 300-400 g of water daily in an adult. • Radioactivity is measured as the number of radioactive disintegrations per s (in Becquerel or Bq per l). One disintegration per s equals one Bq. • Total body water is destributed between two compartments separated by the cell membrane: The intracellular and the extracellular fluid. Essentials This paragraph deals with 1. The three major fluid compartments, 2. Water balance, 3. Body potassium, 4. Body sodium, 5. The indicator dilution principle, 6. The renin- angiotensin-aldosterone cascade, 7. Output contol, 8. Regulation of renal water excretion, and 9. Regulation of renal sodium excretion. Read first about the nephron (paragraph 1 of Chapter 25). 1. The three major fluid compartments The three major body fluid compartments are the intracellular fluid volume (ICV), the interstitial fluid volume (ISV) and the vascular space (Chapter 1, Fig.1-4). Water permeable membranes separate the three compartments, so that they contain almost the same number of osmotically active particles per kg. The three compartments have the same concentration expressed as mOsmol per kg of water or the same freeze-point depression. They are said to be isosmolal, because they have the same osmolality. The so-called lean body mass, which means a body stripped of fat, contains 0.69 parts of water (69%) of the total body weight in all persons. - Such high values are observed in the newborn and in extremely fit athletes with minimal body fat. Babies have a tenfold higher water turnover per kg of body weight than adults do. As an average females have a low body water percentage compared to males. Such differences show sex dependency, but the important factor is the relative content of body fat, since fat tissue contains significantly less water (only 10%) than muscle and other tissues (70%). This is why the relative water content depends upon the relative fat content. The average for most healthy persons is 60% of the body weight. Sedentary, overweight persons contain only 50-55 % water dependent on the body fat content. The relative content of body fat rises with increasing age and body weight, and the relative mass of muscle tissue becomes less. Consequently, the body water fraction falls with increasing body weight and age. Aging implies loss of cells, but the ECV is remarkably
  25. 25. constant through life and under disease conditions. Each body (weight 70 kg) contains 4 mol of both sodium and potassium (ie, the total ion pool). A minor fraction of the potassium is radioactive. The calcium and magnesium content is 25 and 1 mol, respectively. In the renal tubule cells the epithelium is a single layer of cells, joined by junctional complexes near their luminal border (Fig. 25-7). Solutes can traverse the epithelium through transcellular or paracellular pathways. Virtually every cell membrane in the body contains the Na+ - K+ -pump, which maintains the low intracellular Na+ -concentration and develops the negative, intracellular voltage. In the renal tubule cells the Na+ - K+ -pump, is located in the basolateral membrane. Read more about the nephron in Chapter 25 and about hormonal control later in paragraph 8 and 11 of this Chapter. Unfortunately, the simple laws of dilute solutions are unprecise at physiological concentrations. Rough estimates are based on the assumptions that extracellular sodium is associated with monovalent anions and that deviations in osmolality are twice the deviation in plasma sodium concentration. ICV: The dominating intracellular solute is potassium (K+ ), balanced by phosphate and anionic protein, whilst the dominating extracellular solute is NaCl. All compartments have almost the same osmolality 300 mOsmol* kg-1 of water. The thin cell membrane - or the endothelial barrier between ISF and plasma in the vascular phase - cannot carry any important hydrostatic gradient. Water passes freely between the extra- and intra-cellular compartment, as osmotic forces govern its distribution and the membranes are water permeable. Fig. 24-1: The daily water transfer across the gastrointestinal barrier in a healthy standard person. The ICV comprises 26-28 kg out of the total 42-kg of water in a 70-kg person (Fig. 1-4). ECV: The ECV compartment comprises the remaining water (14-16 kg) with most of the water in tissue fluid (interstitial fluid or ISF) and 3 kg of water in plasma (Chapter 1, Fig. 1-4). The size of the ECV compartment is proportional to the total body Na+ . Changes in plasma osmolality indicate problems in water balance. A [Na+ ] in ECV of 150 mmol per kg of plasma water corresponds to a total osmolality of 300 mOsmol per kg. Alterations in plasma-[Na+ ] (osmolality) will be followed by similar changes of the ECV osmolality, because the permeability of of the capillary barrier for Na+ and water is almost equal. The daily water transfer across the gastrointestinal tract amounts to approximately 9 l in each direction (Fig. 24-1). 2. Water balance A healthy person on a mixed diet in a temperate climate receives 1000 ml with the food and drinks 1200 ml daily. Balance is maintained as long as the water loss is the same (Fig. 24-2). Fig. 24-2: The daily water balance in a 70-kg healthy person on a mixed diet. The apparent imbalance between input (2200 ml) and output (2500 ml) is covered by 300 ml of metabolic water. Water is lost in the urine (1500 ml), in the stools (100 ml), in sweat and evaporation from the respiratory tract (900 ml) as a typical example. The total loss of water is 2500 ml, and this corresponds perfectly to the intake plus a normal production of 300 ml of metabolic water per 24 hours (Fig. 24-2).
  26. 26. 3. Body potassium The daily dietary intake of potassium varies with the amount of fruit and vegetables consumed (75-150 mmol K+ daily). More than 90% of the body potassium is located intracellularly. Only a few percent of the K+ in the body pool are found outside the cells and subject to control (Fig. 24-3). The main renal K+ -reabsorption is passive and paracellular through tight junctions of the proximal tubules. Moreover K+ -excretion can vary over a wide range from almost complete reabsorption of filtered K+ to urinary excretion rates in excess of filtered load (ie, net secretion of K+ ). The Na+ -K+ -pump located in the cell membrane, maintains the high intracellular [K+ ] and the low intracellular [Na+ ]. The energy of the terminal phosphate bond of ATP is used to actively extrude Na+ and pump K+ into the cell. The membrane also contains many K+ - and Cl - -channels, through which the two ions leak out of the cell. In myocardial cells, as in skeletal muscle and nerve cells, K+ plays a major role in determining the resting membrane potential (RMP), and K+ is important for optimal operation of enzymatic processes. Under normal conditions, the RMP of the myocardial cell is determined by the dynamic balance between the membrane conductance to K+ and to Na+ . As [K+ ] out is reduced during hypokalaemia, the membrane depolarises causing voltage-dependent inactivation of K+ -channels and activation of Na+ -channels, allowing Na+ to make a proportionally larger contribution to the RMP. Fig. 24-3: The total body K + -pool in a healthy person comprises 4000 mmol with more than 90% intracellularly. The normal ECG and the ECG of a patient with hyperkalaemia is shown to the right. The K+ -permeability is around 50 times larger than the Na+ -permeability, so the RMP of normal myocardial cells (typically: -90 mV) almost equals the equilibrium potential for K + (-94 mV). The excretion of K+ by overload is almost entirely determined by the extent of distal tubular secretion in the principal cells. Any rise in serum [K+ ] immediately results in a marked rise in K+ -secretion. This transport mechanism is controlled by aldosterone and by K+ . Aldosterone stimulates the secretion of K+ and H+ by the principal cells of the renal distal tubules and collecting ducts (Fig. 25-11). This is why chronic acidosis decreases and chronic alkalosis increases K+ -secretion. – Actually, acute acidosis may reduce K+ - secretion. Of the consumed K+ , 75-150 mmol is daily absorbed in the intestine. Since 90% is excreted renally in a healthy person, there must be a minimum in a typical volume of 1500 ml of daily urine with a concentration of (75/1.5) = 50 mM. Normal urinary [K+ ] is at least 30 mM. A high urinary [K+ ] is indicative of a high total body K+ or a high intake of K+ . The normal excretion fraction (Chapter 25) for K+ is 0.10 (10% or 90 mmol of the 900 mmol in the daily filtrate) corresponding to the daily intake (Fig. 24-4). A K+ -poor diet leads to hypokalaemia with less than 20 mmol K+ in the daily urine. A K+ -rich diet triggers a large secretion and a high excretion in the urine (Box 25-1). A low urinary [K+ ]
  27. 27. is indicative of a low total body K+ or of extracellular acidosis with transfer of K + from the cells in exchange of H+ . A low [K+ ] in the distal tubule cells reduces the K+ -excretion. The normal plasma-[K+] level is dependent upon the exchange with the cells, the renal excretion rate, and the extrarenal losses through the gastrointestinal tract or through sweat. Measurement of total and exchangeable body potassium Our natural body potassium is 39K, but we also contain traces of naturally occurring radioactivity (0.00012 or 0.012% is 40K with a half-life of 1.3×109 years). When using this natural tracer, injection of radioactive tracer is avoided. The person to be examined is placed in a sensitive whole body counter, and the total activity of the tracer 40K in the body (S Bq) is measured. Specific activity (SA) is the concentration of radioactive tracer in a fluid volume divided by the concentration of naturally occurring, non-radioactive mother-substance. The concentration of mother-substance is traditionally measured in mmol per l (mM). SA is equal to radioactivity (A) per non-radioactive mass unit, m (ie, A/m in Bq/mol). Following even distribution, the SA for a certain substance must be the same all over the body. SA is preferably measured in plasma (with scintillation counters or similar equipment). Specific activity (SA) is here the number of Bq 40K per mol of mother substance ( 39K) in the whole body. We can calculate all 39K or total body potassium: S/SA mol per whole body - when SA is known to be 0.012% or a fraction of 0.00012. The total body potassium of a healthy person is 4000 mmol. The SA of 40K implies a 40K/39K ratio of 0.48 mmol/4000 mmol (=0.00012). An exchangeable ion pool in our body is the dynamic part of the total specific ion content. The remaining content is fixed as insoluble salts in the bones. The dynamic character implies the use of a dilution principle to measure such a pool. In order to measure the exchangeable body potassium pool, a radioactive tracer is injected, such as 42K with a physical half-life of 12 hours (12.4 hours) and urine is collected. The first urine sample is from the first 12 hours, and the second sample is covering 12 - 24 hours. The total tracer dose given must be adjusted for by the loss of tracer in the urine and by the radioactive decay during the first 12 hours mixing period. The two urine samples obtained are examined for tracer and for natural potassium. The tracer is assumed to distribute just as natural potassium after 12 - 24 hours. When the tracer is distributed evenly in the exchangeable body potassium, its SA must be the same in urine, plasma or elsewhere in the body. The exchangeable body potassium is calculated by Eq. 24-2 . The specific activity for the tracer (SA Bq per mol) is known from the plasma measurements. In this way we measure the exchangeable body potassium. The normal values are 41 mmol 39K per kg body weight for females, and 46 mmol per kg for males. 4. Body sodium ( 23Na) The exchangeable body sodium is easy to measure using the dilution principle and a minimum of equipment. Our natural non-radioactive body sodium is 23Na. We administer the radioactive tracer, 24Na, with a physical half-life of 15 hours. We have to use a total period of 30 hours to secure even distribution in the ECV. The total tracer dose given, must be adjusted for by the loss of tracer in the urine, and the radioactive decay of 24Na (see the decay law in Chapter 1). The exchangeable body sodium is calculated by Eq. 24-2. We know the specific activity for the tracer (SA Bq/mol) from the plasma measurements; 23
  28. 28. therefore calculation of the exchangeable body Na is easy. The normal value for exchangeable body sodium is 40 mmol/kg of body weight. In a patient with a body weight of 75 kg the exchangeable sodium is (75 × 40) = 3000 mmol. The non-exchangeable sodium is fixed in the bones. The total body sodium is measured following discrete radiation with a method called neutron activation analysis. The whole body of the patient is exposed to radiation with neutrons. A small fraction of the natural 23Na now becomes radioactive sodium ( 24Na) by uptake of an extra neutron. A sensitive whole body counter records the radiation from 24Na. Now we can calculate the total body sodium. Normally, the total body sodium is 1000 mmol larger than the exchangeable sodium due to the fixed sodium content of the bones (1000 + 3000 mmol = 4000 mmol 23Na). Fig. 24-4: Body fluid electrolytes. Water permeable membranes separate the three compartments, which contain almost the same number of osmotically active particles per kg. The sum columns of electrolyte equivalents in muscle cells are essentially higher than the extracellular sum columns of equivalents, because cells contain proteins, Ca2+, Mg 2+ and other molecules with several charges per particle (Fig. 24-4). The above columns show the ionic composition per kg of water, so we have 150 mmol of Na per kg of plasma water. Normally, one litre of plasma has a weight of 1.040 kg and contains 10% of dry material. Consequently, one litre of plasma contains 0.940 l of water, and the rest consists of plasma proteins and small ions. Thus the fraction of water in plasma (F water) is typically 0.94. 5. The indicator dilution principle Mass conservation is always the underlying principle. The amount of indicator n mol distributes in V litres of distribution volume. We measure the concentration Cp in mM, following even distribution, and calculate V: V = n/C p . Errors: Uneven distribution of indicator introduces a systematic error. - A non- representative concentration of indicator in the plasma makes it insufficient to correct for plasma proteins alone. - Loss of indicator to other compartments is inevitable. - Elimination or synthesis of indicator in the body occurs as frequent errors. - The indicator may be toxic or in other ways change the size of the compartment to be measured. Total body water, ECV, plasma volume, and the elimination rate constant are measured as follows: 5 a. Total body water Total water is measured by the help of the dilution principle. Tritium marked water is a good tracer. The equilibrium period is 3-6 hours. n mol of indicator divided by Cp mmol of indicator per l is equal to the distribution volume (V) for the indicator. Healthy adolescents and children have normal values around 60% of the body weight assuming one l of water to be equal to one kg. Adult males and females with a sedentary life style and larger fat fractions contain only 50% of water. 5 b. The extracellular fluid volume (ECV) is measured by administration of a priming dose of inulin intravenously. Then inulin is infused to maintain a steady state with constancy of the plasma concentration of inulin (Cp ).
  29. 29. The patient then urinates, and the infusion is stopped with collection of a plasma sample. For the next 10 hours the patient collects his urine, which makes it possible to measure all the body inulin present at the end of the infusion (n mol) assuming all inulin excreted. Dividing n with Cp gives the volume of distribution (V) after correcting for the difference in protein concentration between plasma and ISF (Eq. 24-1). Chromium-ethylene-diamine-tetra-acetate ( 51Cr-EDTA) is a chelate with a structure that cannot enter into cells. The chelate molecule contains radioactive Cr, making it easy to measure. The 51Cr-EDTA distributes and eliminates itself in the extracellular fluid volume (ECV) just as inulin and is therefore used to measure ECV. – For clearance measurements, we inject a single dose intravenously, and draw blood samples every hour for 5 hours. The clearance of 51Cr-EDTA is independent of Cp and a good estimate of GFR just like the inulin clearance. Since the indicator is cleared from the ECV only, it is possible to measure its size. Such methods - including renal lithium reabsorption - are important during renal function studies. Normal values for ECV are approximately 20% of the body weight or 14- 17 kg. Chronically ill patients with debilitating diseases often maintain their ECV remarkably well in spite of marked reductions in the cell mass of their body. 5 c. The plasma volume Also here, the dilution principle is used. The indicator for plasma volume can be Evans Blue (T 1824) that binds to circulating plasma albumin. A small dose of albumin, marked with radioactive iodine, is also a good indicator (iodine 131 has a physical half-life of 8 days). The indicator concentration in plasma (Cp ) is measured every 10-min for an hour after the administration, and the log of Cp is plotted with time. Extrapolation to the time zero determines the maximum concentration of indicator in plasma. This corrects for the biological loss, while the indicator distributes itself in the plasma phase. The tracer dose divided by Cp at time zero provides us with the intravascular plasma volume. Normal values for the plasma volume are close to 5% of the body weight. In diabetics and hypertensive patients the tracer is lost more readily through their leaky capillaries to the interstitial fluid than in healthy persons (increased transcapillary escape). 6. The renin-angiotensin-aldosterone cascade Macula densa is described in paragraph 9 of Chapter 25. The most likely intrarenal trigger of the renin-angiotensin-aldosterone cascade is the falling NaCl concentration of the reduced fluid flow at the macula densa in the distal renal tubules (Fig. 24-5). The NaCl concentration at the macula densa falls, when we lose extracellular fluid, move into the upright position and when the blood pressure falls. Renin is a proteinase that separates the decapeptide, angiotensin I, from the liver globulin, angiotensinogen. When angiotensin I passes the lungs or the kidneys, a dipeptide is separated from the decapeptide by angiotensin converting enzyme (ACE). This process produces the octapeptide, angiotensin II. Angiotensin II has multiple actions that minimize renal fluid and sodium losses and maintain arterial blood pressure. 1. Angiotensin II stimulates the aldosterone secretion by the adrenal cortex, and through this hormone it stimulates Na+ -reabsorption and K+ -(H+ )-secretion in the
  30. 30. distal tubules (Fig. 24-5). - Angiotensin II is in itself a potent stimulator of tubular Na+ -reabsorption. 2. Angiotensin II inhibits further renin release by negative feedback. 3. Angiotensin II constricts arterioles all over the body including a strong constriction of the efferent and to some extent also the afferent arteriole. Hereby, the renal bloodflow (RBF) and to a lesser extent the glomerular filtration rate (GFR) is reduced. 4. Angiotensin II inhibits the absolute proximal tubular reabsorption – contributing to the reduction of GFR. 5. Angiotensin II enhances sympathetic nervous activity. Fig. 24-5: The renin-angiotensin-aldosterone cascade. Sympathetic stimulation of the renal nerves stimulates renin secretion directly via b- adrenergic receptors on the JG cells just as falling blood pressure in the preglomerular arterioles. - b-blocking drugs and angiotensin II inhibit the renin secretion (Fig 24-5). The combined effects from the whole renin cascade is extracellular fluid homeostasis. In contrast, exposure to stress and painful stimuli triggers the combined sympatho- adrenergic system with release of catecholamines, gluco- and mineralo-corticoids, and ACTH from the hypophysis. ACTH stimulates further the secretion of the glucocorticoid, cortisol, from the adrenal cortex. 7. Output control The body uses output control, when it is overloaded with water or with sodium. The most important osmotically active solute in ECV is NaCl, because it only passes into cells in small amounts. Urea, glucose and other molecules with modest concentration gradients are without importance, because they distribute almost evenly in the fluid compartments. Healthy persons use two primary control systems: 1) The osmolality (osmol per kg of water) or ion concentration controls our elimination of water. 2) The change of blood volume (ECV) or pressure controls sodium excretion - not osmolality. Only when the arterial blood pressure falls drastically the body will drop its protection of normal concentration. In such a disease state large amounts of ADH molecules are released in an attempt to improve the volume and blood pressure. 8. Regulation of renal water excretion The primary control of the renal water excretion is osmolality control (Fig. 24-6). Since 2/3 of the body water normally is located within the cells, this is also an intracellular volume control. Following water deprivation even an increase in plasma osmolality of only one per cent stimulates both the hypothalamic osmoreceptors and similar (angiotensin-II-sensitive) thirst receptors. Thirst may increase the water intake of the individual and thus increase the ECV, with negative feedback to the thirst receptors. Activation of the hypothalamic osmoreceptors and thirst receptors increases the hypothalamic neurosecretion to the neurohypophysis and releases antidiuretic hormone (ADH or vasopressin). Hyperosmolality elicits a linear increase in plasma ADH, which causes water retention (Fig. 24-6) until isosmolality is reached. ADH increases the reabsorption of water from the fluid in the renal cortical and medullary collecting ducts. ADH binds to receptors on the basolateral surface of the tubule cells,
  31. 31. where they liberate and accumulate cAMP. This messenger passes through intermediary steps across the cell to the luminal membrane, where the number of water channels (aquaporin 2) are increased. The luminal cell membrane is thus rendered water-permeable, which increases the renal water retention. The increased water reabsorption leads to a small, concentrated urine volume (antidiuresis), and a net gain of water that returns ECF osmolality towards normal. Initially, osmolality control overrides blood volume control. Fig. 24-6: Primary osmolality control of the renal water excretion. ADH and thirst systems maintain osmolality and ICV within narrow limits. Water overload decreases ECF osmolality and has the reverse effect, because the hypothalamic osmoreceptors suppress the ADH release, and the renal water excretion is increased already after 30 min (Fig. 24-6). When a person rapidly drinks one litre of water, the intestine absorbs water. Ions diffuse into the intestinal lumen and the blood osmolality falls causing a block of the ADH secretion (Fig. 24-6). Pure water is distributed evenly in all three body fluid compartments – just like intravenous infusion of one litre of 5% glucose in water. Intake of one l of isotonic saline implies ECV expansion, without dilution of body fluids. This expansion will not increase the urine volume much, so the increased ECV can be sustained for many hours. An intravenous infusion of one l of large dextran molecules (macrodex) stays mainly in the vascular space. 9. Regulation of renal sodium excretion In healthy persons, changes of blood volume (or ECV) or blood pressure control sodium excretion (Fig. 24-7). The dominating cation of the ECV is Na+ . The sodium intake is balanced by the sodium excretion as long as the thirst and other homeostatic systems are functional. During conditions where sodium intake exceeds renal sodium excretion, total body sodium and ECV increase. Conversely, total body sodium and ECV decrease, when sodium intake is lower than renal sodium excretion. This is because volume-pressor-receptors detect the size of the circulating blood volume (ECV) or pressure, and effector mechanisms adjust the renal sodium excretion accordingly. The volume-pressor-receptors are widely distributed. Low-pressure receptors are found in the pulmonary vessels and in the atria. An increased blood volume can also increase the arterial blood pressure and stimulate the well-known high-pressure baroreceptors in the carotid sinus and the aortic arch. Increased arterial pressure reduces sympathetic tone – also in the kidneys, whereas decreasing arterial pressure enhances sympathetic tone and renal salt retention. Arterial pressure receptors are also located in the renal preglomerular arterioles. Both stimuli in Fig. 24-7 release renin from macula densa, whereby angiotensin II and aldosterone is secreted (both sodium retaining hormones). A decrease in circulating blood volume leads to a decrease in NaCl delivery to the macula densa and release of the renin cascade. Conversely, an increase in circulating blood volume with increased NaCl delivery to the macula densa suppresses renin release and increases sodium excretion (Fig. 24-7). Fig. 24-7: Primary blood volume-pressure control of the renal Na+ -excretion. The effective circulating blood volume is protected – also during shock (Na+ -retention) and during hypertension (natriuresis). Increased salt intake increases blood volume and leads to natriuresis, possibly augmented by release of ANP (see below), nitric oxide and other factors. The excretion of Na+