Too many bananas

Hyperkalemia is a result of potassium excess. It can be result of aldosterone deficiency causing potassium retention (too little excretion in the kidneys) (1p435). Also possible trauma that damages cells could cause released potassium to overload kidneys (1p435).

Reference List

1. Nowak TJ, Handford AG. Pathophysiology: Concepts and Applications for Health Professionals. New York: McGraw-Hill, 2004.

A horse named charley

Although we may fight for it, in the end we just can't stop people from naming their horses "Charlie". But maybe we can help them with an involuntary contraction or spasm causing a muscle cramp, sometimes called a "charley horse". Usually they occur due to an overused or injured muscle, but can also be caused by lack of minerals such as potassium (1). So, before and after exercise, eat your bananas.

Reference List
1. MedlinePlus. Charley Horse. Medline Encyclopedia. Available at: http://www.nlm.nih.gov/medlineplus/ency/article/002066.htm

Respiratory vs metabolic acidosis

The symptoms of respiratory and metabolic acidosis are pretty similar. In both you see generalized weakness, fatigue, nausea, vomiting and CNS depression (1). How does a blood test distinguish from the two?

Respiratory acidosis differs from metabolic acidosis because it is a result of impaired pulmonary function causing a build-up of CO2 that lowers pH instead of one that is mainly caused by increased acid metabolic products (1). A blood test can indicate between the two by measuring pH, bicarbonate (HCO3-) and carbon dioxide (PCO2) (1).

If the test reveals acidic extracellular fluid (ECF) but normal CO2 indicating adequate respiratory function or low PCO2 indicating active ventilation response, then pH disruption has a metabolic source (1). An elevated PCO2 indicates inability to clear CO2 and the drop in pH is a result of carbonic acid formed (1).

Now if for any reason you accidentally swallow antifreeze, methanol or high doses of aspirin, you should know it can potentially cause either acidosis. To correct acidosis you use sodium bicarbonate (1). The same as baking soda.

Reference List

1. Nowak TJ, Handford AG. Pathophysiology: Concepts and Applications for Health Professionals. New York: McGraw-Hill, 2004.

Not enough bananas

Potassium, the main cation in the cells, is often lost through perspiration, feces and urine (1). A deficit of potassium is called hypokalemia (1). Hypokalemia may occur simply due to inadequate dietary potassium intake, although it is more likely due to a case where there is excessive loss of potassium (1).

Various reasons can cause excessive loss of potassium such as vomiting, heavy sweating or chronic diarrhea (1). It can often result of laxative abuse or drugs such as diuretics (1). It is possible to develop hypokalemia due to inappropriate IV fluid (1).The signs of hypokalemia are weakness, muscle twitching and depressed neuromuscular reflexes (1).

Reference List
1. Nowak TJ, Handford AG. Pathophysiology: Concepts and Applications for Health Professionals. New York: McGraw-Hill, 2004.

Trans fats increase diabetes risk more than saturated fats

Saturated fats including trans fat can lead to a increased risk of cardiovascular disease mainly by raising cholesterol and causing a poor LDL:HDL ratio (1). Trans fat is thought to be more atherogenic because it has also been found to lower HDL cholesterol in studies (1-3).

But what about diabetes risk?

In 2006 a review on the literature of trans fats versus saturated fats in insulin resistance noted that while high intake of saturated fats may promote insulin resistance, it is too early to determine if trans fats create increased risk(3). However, a 2008 rat study published in Asia Pac J Clin Nutr (2) showed that rats fed a diet higher in saturated fats had decreased peripheral insulin sensitivity, but that if trans fat was included the effect was greater.

Biochemically the reason for the effects on insulin sensitivity from dietary trans fat may have to do with its potential interference with cell membrane functions and decreasing insulin concentration (3-5). Ultimately both saturated and trans fats decrease insulin concentration, but trans fat more so (3-5). Interestingly, a review in Atheroscler Suppl pointed out that conjugated trans fat appears to be the “most dramatic” of all fatty acids in impairing insulin sensitivity (5).

Reference List
1. Gropper SS, Smith JL, Groff JL. Advanced Nutrition and Human Metabolism. Belmont, CA: Thomson Wadsworth, 2009.
2. Ghafoorunissa G. Role of trans fatty acids in health and challenges to their reduction in Indian foods. Asia Pac J Clin Nutr 2008;17 Suppl 1:212-5.
3. Odegaard AO, Pereira MA. Trans fatty acids, insulin resistance, and type 2 diabetes. Nutr Rev 2006;64:364-72.
4. Bhathena SJ. Relationship between fatty acids and the endocrine and neuroendocrine system. Nutr Neurosci 2006;9:1-10.
5. Riserus U. Trans fatty acids and insulin resistance. Atheroscler Suppl 2006;7:37-9.

Do eggs raise cholesterol?

The presence of ovomucin, a natural trypsin inhibitor in eggs, can help block some of egg cholesterol absorption and bile acid reabsorption through enterohepatic circulation (1). Despite ovomucin, however, there does appear to be enough dietary cholesterol in eggs absorbed that can potentially cause increased cholesterol levels (2;3).

Reference List
1. Nagaoka S, Masaoka M, Zhang Q, Hasegawa M, Watanabe K. Egg ovomucin attenuates hypercholesterolemia in rats and inhibits cholesterol absorption in Caco-2 cells. Lipids 2002;37:267-72.
2. Levy Y, Maor I, Presser D, Aviram M. Consumption of eggs with meals increases the susceptibility of human plasma and low-density lipoprotein to lipid peroxidation. Ann Nutr Metab 1996;40:243-51.
3. Applebaum-Bowden D, Hazzard WR, Cain J, Cheung MC, Kushwaha RS, Albers JJ. Short-term egg yolk feeding in humans. Increase in apolipoprotein B and low density lipoprotein cholesterol. Atherosclerosis 1979;33:385-96.

Good and bad reasons to cook eggs

Raw egg white contains avidin. As dietary protein is digested, the presence of avidin can bind to biotin tightly preventing its absorption into the body (1). Because biotin is used as a prosthetic group in acetyl CoA carboxylase, a biotin deficiency can then inhibit the carboxylation reaction catalyzed by acetyl CoA carboxylase that converts malonyl CoA from acetyl CoA and CO2 (2). The conversion to malonyl CoA is ultimately the reaction by which carbons of a fatty acid are contributed to by acetyl CoA (2). Cooking destroys the avidin, which is a good thing.

But wait, an article in the latest Journal of Nutrition explains that Maillard reaction products (result of heating proteins and sugars) may alter amino acid availability and reduce digestibility of certain proteins (3). It would lead to believe that you'd want your protein raw or microfiltered versus fried or treated with ultra-high temperatures. Sure enough, you'll get more protein from a raw egg, plus enzymes and vitamins.

In the end, if you're going to eat eggs at all (see next post on cholesterol), it's probably best to cook the egg minimally and take a quality multi-vitamin and an enzymes supplement. That way you don't accidentally get salmonella.

Reference List

1. Brody T. Nutritional Biochemistry. San Diego: Academic Press, 1999.
2. Gropper SS, Smith JL, Groff JL. Advanced Nutrition and Human Metabolism. Belmont, CA: Thomson Wadsworth, 2009.
3. Lacroix M, Bon C, Bos C et al. Ultra high temperature treatment, but not pasteurization, affects the postprandial kinetics of milk proteins in humans. J Nutr 2008;138:2342-7.

Lovastatin versus cholestyramine for familial hypercholesterolemia

Along with the recommendation of exercise and a healthy diet (including a bit of red wine daily), both lovastatin and cholestyramine can be used in the treatment of familial hypercholesterolemia (1;2).

While lovastatin works as a HMG CoA reductase inhibitor to reduce cholesterol synthesis in the liver, cholestyramine acts as a bile acid-binding resin that increases fecal removal of cholesterol (1p152;3-4).

Reference List
1. Gropper SS, Smith JL, Groff JL. Advanced Nutrition and Human Metabolism. Belmont, CA: Thomson Wadsworth, 2009.
2. Netdoctor.co.uk. Familial hypercholesterolemia. Available at: http://www.netdoctor.co.uk/diseases/facts/familialhypercholesterolaemia.htm.
3. Netdoctor.co.uk. Questran (colestyramine). Available at: http://www.netdoctor.co.uk/medicines/100002209.html.
4. Medicine.net. Lovastatin (oral). Available at: http://www.medicinenet.com/lovastatin-oral/article.htm.

Grape seed extract slows oxidation of LDL

We know that antioxidants such as vitamin E may slow development of atherosclerosis by reducing oxidation of LDL (1). So I bring to your attention a just-released study of note on antioxidant procyanidins of grape seed extract (2). The study was proposes a “corrective role” of the procyanidins on foam cells because of results in vitro that suggest the antioxidant effects reduce cholesterol and lipid accumulation as well as modulate expression of genes that play a role in inflammation (2).

Reference List
1. Gropper SS, Smith JL, Groff JL. Advanced Nutrition and Human Metabolism. Belmont, CA: Thomson Wadsworth, 2009. 2. Terra X, Fernandez-Larrea J, Pujadas G et al. Inhibitory effects of grape seed procyanidins on foam cell formation in vitro. J Agric Food Chem 2009;57:2588-94.

What happens when you are acyl CoA dehydrogenase deficient?

Without acyl CoA dehydrogenase to initiate the first step of mitochondrial beta-oxidation, your ability to metabolize fats is inhibited (1). That is, the enzyme—one of four depending on fatty acid chain lengths—catalyzes the formation of the double bond between alpha- and beta-carbons, which then are degraded to two-carbon acetyl CoA units (1p159).

Because the body relies on the production of acetyl CoA from its storage of fat for energy, the lack of acetyl CoA dehydrogenase and in its capacity to produce beta-oxidation causes the body to end up in a hypoglycemic (no glucose) and hypoketotic state (no ketones from oxidation of fatty acids) (1p159;2-3).

Reference List
1. Gropper SS, Smith JL, Groff JL. Advanced Nutrition and Human Metabolism. Belmont, CA: Thomson Wadsworth, 2009.
2. PerkinElmer Genetics. Multiple Acyl-CoA Dehydrogenase Deficiency. Available at: http://www.perkinelmergenetics.com/MultipleAcylCoADehydrogenaseDeficiency.htm.
3. STAR-G. Genetic Fact Sheet for Parents: Fatty Acid Oxidation Disorders. Available at: http://www.newbornscreening.info/Parents/fattyaciddisorders/VLCADD.html.

Blaming Burger King: The Genesis of Atherogenesis

In a previous post I wrote of my grandpa who eventually died of a myocardial infarction resulting from atherosclerosis, of which I attribute to a diet of $1 Whoppers. So cheap, so tempting was this Burger King specialty that it is perhaps what also took my grandmother via cardiovascular disease.

Apart from a “whopping” amount of calories each received on the diet, the biochemical backup to my conclusions has to do chiefly with the kind of macronutrients they got. Specifically the type of fat received is of focus because in the Whopper is particularly saturated (and likely some trans fat) as well as cholesterol.

Well and good is knowledge that a diet high in fat overall have a positive correlation with cardiovascular disease, but consumption of a diet high in saturated and trans fat is hypercholesterolemic, causing a shift to a poor ratio of higher “bad” LDL to “good” HDL cholesterol, according to latest research (1p155).

The circulation of extra LDL, which is the major transporter of cholesterol in the serum, is linked with atherogenesis mainly as LDL becomes oxidized (1p176). The oxidized LDL produces a toxic effect on endothelial cells possibly by attracting blood-borne monycytes, transforming them into macrophages and trapping them in endothelial spaces (1p176).

The resulting “foam cells” (macrophages engorged with lipids, mainly cholesterol) release cytokines that attract yet more macrophages that end up similarly (1p155). Together the foam cells, along with damaged smooth muscle cells, form a plaque much appearing in the form of a fatty streak that, if large enough, narrows the lumen to the point where blood flow is restricted (1p155).

Had my grandparents simply opted to focus their lipid-loving taste buds on monounsaturated and polyunsaturated fats, then their story would have been different. These fats present reverse results to the others causing hypocholesterolemic effects (1p155). Adoption of n-3 polyunsaturated fatty acids, specifically, may have even interfered with the platelet aggregation caused by fatty acid displacement and inflammatory cytokines that are involved in producing plaque formation as well as reduced tryacylglycerol concentration in the serum (especially from EPA/DHA-rich fish oil) (1p155).

Unfortunately this knowledge was not available to my grandparents. But may they rest in peace knowing their end was a wake-up call to their grandson.

Reference List
1. Gropper SS, Smith JL, Groff JL. Advanced Nutrition and Human Metabolism. Belmont, CA: Thomson Wadsworth, 2009.

Nephrotic versus nephritic syndrome

Both glomerular disorders cause impaired filtration in the kidneys.

The nephrotic syndrome is a condition of large-scale proteinuria (1p405). Its cause is damaged glomeruli that are unable to retain protein resulting in hypoalbuminea that creates a fall in blood osmotic pressure and systemic edema (1p405). Hyperlipidemia also occurs because of increased liver synthesis of lipoprotein to respond to low plasma protein (1p405). In addition to treatment for the underlying reason for the syndrome (which can include antibiotics, diuretics or statins), treatment is necessary to reduce protein in the urine and can include ACE inhibitors or ARBs (2).

The nephritc syndrome is a result of inflammatory damage restricting filtration allowing red blood cells to escape to urine causing hematuria (1p406). There is less urine output, or oliguria, which causes nitrogenous wastes to accumulate causing azotemia (1p406). Systemic hypertension also results since the increased blood pressure is used as a way to compensate for lower filtration and retained fluid (1p406). Some protein loss can occur, but not nearly as much as in nephrotic syndrome (1p406). Treatment for underlying causes for infection or HIV/HCV is necessary, but in some acute or severe cases complete renal failure is the end (1p407)

Reference List
1. Nowak TJ, Handford AG. Pathophysiology: Concepts and Applications for Health Professionals. New York: McGraw-Hill, 2004.
2. Mayo Clinic. Nephrotic syndrome: Treaments. Available at: http://www.mayoclinic.com/health/nephrotic-syndrome/DS01047/DSECTION=treatments-and-drugs.

Jaundice types

When bilirubin levels are elevated, a yellow-brown color can be visible on the skin (1). The jaundice can be indicative of hemolytic, hepatocellular or cholestatic jaundice (1).

Hemolytic jaundice results from red blood cells rupturing excessively and release of hemoglobin (1). It happens when red cell membrane abnormalities such as hemolytic anemia are present (1).
Hepatocellular jaundice is a failur of liver to take up or conjugate bilirubin (1). Damage to liver cells due to infection, tumors, drugs or toxins can be at fault here (1). In newborns it may just be that the liver conjygation enzyme and excretion systems are just not functional yet, and goes away when liver cells mature (1).

Cholestatic jaundice occurs when bile fails to drain from the liver in normal fashion, which interferes with cell's ability to excrete conjugated bilrubin (1). Its cause may be liver cell damage, or, more commonly, bile duct obstruction (1).

Reference

1. Nowak TJ, Handford AG. Pathophysiology: Concepts and Applications for Health Professionals. New York: McGraw-Hill, 2004, p375-6.

Hepatoprotector

In Argentina, where my mother’s from, it is common to take a “hepatoprotector” supplement while eating to help deal with digestion. One of these is artichoke extract of which I take whenever I eat a big meal. Perhaps my habit was largely based on anecdotal evidence, but some research has been appearing about the benefits.

A few studies in rats and humans suggest the extract can have hepatoprotective activity due to antioxidant polyphenols(1-3). These appear to act by encouraging bile synthesis as well as protecting hepatocytes from oxidative stress (1-3).
Reference List

1. Miccadei S, Di VD, Cardinali A et al. Antioxidative and apoptotic properties of polyphenolic extracts from edible part of artichoke (Cynara scolymus L.) on cultured rat hepatocytes and on human hepatoma cells. Nutr Cancer 2008;60:276-83.
2. Speroni E, Cervellati R, Govoni P, Guizzardi S, Renzulli C, Guerra MC. Efficacy of different Cynara scolymus preparations on liver complaints. J Ethnopharmacol 2003;86:203-11.
3. Adzet T, Camarasa J, Laguna JC. Hepatoprotective activity of polyphenolic compounds from Cynara scolymus against CCl4 toxicity in isolated rat hepatocytes. J Nat Prod 1987;50:612-7.

Type 1 diabetes and hypertriglyceridemia

When uncontrolled type 1 diabetes takes hold, then insulin isn’t around to induce full activity of lipoprotein lipase, which is the enzyme that hydrolyzes triglycerides in chylomicrons and VLDL to produce fatty acids (1-2). The VLDL cholesterol becomes overproduced and then lipoproteins rich in triglycerides tend to produce hyperglyceridemia (1;3-4).

To diagnose the condition a lipid analysis can determine elevated triglyceride levels and increased VLDL cholesterol (5). Presence of chylomicrons would confirm the problem (5). And to make a definitive judgment, lipoprotein lipase or its co-factor apoliprotein CII can be tested for to see if there’s a deficiency, which could be genetic or due to a disorder (5).

Reference List

1. Nowak TJ, Handford AG. Pathophysiology: Concepts and Applications for Health Professionals. New York: McGraw-Hill, 2004.
2. Gropper SS, Smith JL, Groff JL. Advanced Nutrition and Human Metabolism. Belmont, CA: Thomson Wadsworth, 2009.
3. WebMD. Hypertriglyceridemia. eMedicine. Available at: http://emedicine.medscape.com/article/126568-overview
4. Habermann TM, Ghosh A. Mayo Clinic Internal Medicine Concise Textbook. Mayo Clinic Scientific Press and Informa Healthcare, Inc, p 208.
5. WebMD. http://emedicine.medscape.com/article/126568-diagnosis

Why a carb-free diet?

OK, let’s talk about what happens when on a carb-free diet. Normally the diet would not be recommended. Here's why:

Without carbs the liver can do fine using fatty acids converted to triacylglycerols and phospholipids for oxidation in hepatocyte mitochondria (1p167), but the brain and muscles want glucose and, thus, gluconeogenesis occurs using up lactate and alanine and eventually breaking down protein to use amino acids (1p97-98).

Ketones, at a point of starvation of glucose, can end up being an undesired fuel for brain and muscle, but this can be accompanied by a dangerous acid-base balance known as ketosis (1p160). Because of direct oxidation of fatty acids through the TCA cycle, the acetyl CoA can end up in an “overflow” pathway promoting ketone bodies like acetoacetate, beta-hydroxybutyrate and acetone (1p159).

If one wishes to prevent diabetes, however, a carb-free diet may be helpful. According to a German study on mice, a carb-free diet eliminated the hyperglycemia that would normally develop into beta-cell failure, although the mice became morbidly obese (2). Another study confirmed the results: a carb-free diet reduced sensitivity to insulin (3).

In other situations where it is vital to avoid hyperglycemia, a carb-free diet may also be used. An example is after a severe head injury, when possibility of ischemia may occur, because in such cases, carbs may worsen the neurological outcome (4).

Reference List

1. Gropper SS, Smith JL, Groff JL. Advanced Nutrition and Human Metabolism. Belmont, CA: Thomson Wadsworth, 2009.

2. Mirhashemi F, Kluth O, Scherneck S, et al. High-fat, Carbohydrate-Free Diet Markedly Aggravates Obesity but Prevents β-Cell Loss and Diabetes in the Obese, Diabetes-Susceptible db/db Strain. Obesity Facts 2008;1:292-297. Available at: http://content.karger.com/ProdukteDB/produkte.asp?Aktion=ShowPDF&ArtikelNr=000176064&Ausgabe=244083&ProduktNr=233731&filename=000176064.pdf.

3. Bainbridge HW. The reduced sensitivity to insulin of rats and mice fed on a carbohydrate-free, excess-fat diet. J Physiol 1925;60:293-300.

4. Ritter AM, Robertson CS, Goodman JC, Contant CF, Grossman RG. Evaluation of a Carbohydrate-Free Diet for Patients with Severe Head Injury Journal of Neurotrauma. August 1996, 13(8): 473-485. doi:10.1089/neu.1996.13.473.

Laxatives 101

The objective of a laxative is to promote defecation. There are a number of agents. They each have different mechanisms.

• A bulk-forming agent like methylcellulose or psyllium hulls do just that, form bulk, which increase intestinal motility. Psyllium hulls are a favorite of mine, because it also helps lower cholesterol and can be used long-term.
  
• If the laxative is osmotic or saline, such as magnesium ion, then the mechanism is to draw water from mucosa using high ion concentration to create luminal osmotic pressure.
  
• An irritant or stimulant agent, such as anthraquinones from senna or aloe vera latex, bother the intestinal mucosa and promote secretion and enhance distention. They can be dangerous. High doses of anthraquinones inhibit electrolyte reabsorption and induce depletion of potassium while long-term use can irritate mucous membranes.
  
• In addition, when stools are hard, sometimes a different kind of laxative is used such as docusate potassium, which helps soften stools by emulsifying, mixing water and fat. This can also be promoted by soluble fiber such as guar gum.

Reference List

Nowak TJ, Handford AG. Pathophysiology: Concepts and Applications for Health Professionals. New York: McGraw-Hill, 2004.

Jellin JM, Gregory PJ, and et al. Pharmacist's Letter/Prescriber's Letter Natural Medicines Comprehensive Database, 10th ed. 2008. Stockton, CA, Therapeutic Research Faculty. 2. Davis RH.

So you have colitis?

If you have ulcerative colitis or Crohn’s, then it’s a good time to wish you’d been born Chinese because gene markers have pretty much pinned both these inflammatory bowel diseases on those with Jewish and European ancestry (1;2). Apparently, your ancestors developed a phenotype with some kind of bad regulation of an immune mechanism (2). It’s kind of like an allergy, only the response causes a bunch of mucosal damage in your gut (2).

The cramping, diarrhea and fever is a pain (2). And colitis probably comes with blood in the stool, which could be serious since losing fluid and electrolytes, and blood loss, can put your body into shock (2). Most people (85 percent) only have mild-moderate symptoms, but 15 percent have severe cases of which 15 percent die (2). Worse yet is that colitis and Crohn’s can lead to other problems over time like inflamed joints, liver damage and even cancer (2). When you have colitis for a long time, cancer risk increases significantly (2). If you haven’t already, you might need a colonoscopy to determine how susceptible you might be to cancer (3). Getting treated early is key. You might need anti-inflammatories, immunosuppressives and antidiarrheal drugs (2). By keeping colitis in check, hopefully doctors won’t have to remove any part of your colon (2).

What else should you do? What about dietary therapy?

Well, you’ve got to think about nutrition. Fact is that mucosal damage from colitis impairs digestion leading to possible malabsorption and, thus, malnutrition (2). Poor nutrition means your increasing chances of other problems (like the cancer risk). You might, for example, take a consider taking digestive enzymes to help digest food correctly (making up for possible lack of pancreatic enzymes) and a multi-vitamin for extra nutrients (2).

You should consider probiotics/prebiotics. The long ancestral history of Europeans and Jews drinking fermented milk products might play a role in all of this. The genetic susceptibility to inflammatory bowel diseases is proving to be exacerbated by wrong bacteria in your gut, especially if there’s an overgrowth in the small intestine (where they should not be) (4-11). So, probiotics (such as lactobacilli in yogurt) and prebiotics (soluble fiber that helps grow probiotics) are showing great promise. The trick is to eradicate bad bacteria with antibiotics, then to populate and grow the good bacteria in your gut; the good bacteria protect mucosal cells and may even help regulate immune response by controlling pro-inflammatory cytokines; plus, they can help improve lactose absorption (4-11).

Changing the oils in your diet could offer long-term benefits in reduced inflammation. Basically you’d avoid the pro-inflammatory omega-6 oils from canola and soy, and instead use mono- and polyunsaturated fats from olive oil and fish oil (rich in EPA/DHA fatty acids). A few studies show that following that advice can help reduce inflammation in the gut and, along with antioxidants, guard against mucosal damage from reactive oxygen (12-15).

Because the mucosal damage occurs due to reactive oxygen, it makes sense to supplement with superoxide dismutase (SD) (16). The enzyme acts like an antioxidant by catalyzing reactive oxygen (superoxide anion) to regular hydrogen peroxide and oxygen (16). Problem is you can’t absorb oral SOD, but new research is showing that maybe you would be able to if it’s lecithinized (16). Other antioxidants to supplement that have shown clinical promise would be vitamin C, E, selenium and citrus bioflavonoids (14;15).

So here’s a summary on diet: start with taking a regular digestive enzymes supplement and multivitamin, talk to your doctor about antibiotics, then get your prebiotics (increase soluble fiber gradually) and probiotics, take a quality fish oil supplement, use olive oil and don’t use the pro-inflammatory oils with omega-6 like soy or canola oil. Lastly, get your antioxidants (from a supplement or from plenty of fruits and vegetables) and if you can find the lecithinized SOD, get that too. Do all this, try to avoid cancer and other terrible problems.

Reference List

1. Yun J, Xu CT, Pan BR. Epidemiology and gene markers of ulcerative colitis in the Chinese. World J Gastroenterol 2009;15:788-803.
2. Nowak TJ, Handford AG. Pathophysiology: Concepts and Applications for Health Professionals. New York: McGraw-Hill, 2004.
3. Korelitz BI. Crohn's colitis versus ulcerative colitis: should surveillance for dysplasia and cancer differ? Nat Clin Pract Gastroenterol Hepatol 2009;6:144-5.
4. Mitsuyama K, Sata M. Gut microflora: a new target for therapeutic approaches in inflammatory bowel disease. Expert Opin Ther Targets 2008;12:301-12.
5. Hedin C, Whelan K, Lindsay JO. Evidence for the use of probiotics and prebiotics in inflammatory bowel disease: a review of clinical trials. Proc Nutr Soc 2007;66:307-15.
6. Gionchetti P, Rizzello F, Campieri M. Probiotics and antibiotics in inflammatory bowel disease. Curr Opin Gastroenterol 2001;17:331-5.
7. Gionchetti P, Lammers KM, Rizzello F, Campieri M. Probiotics and barrier function in colitis. Gut 2005;54:898-900.
8. Lammers KM, Vergopoulos A, Babel N et al. Probiotic therapy in the prevention of pouchitis onset: decreased interleukin-1beta, interleukin-8, and interferon-gamma gene expression. Inflamm Bowel Dis 2005;11:447-54.
9. Brown AC, Valiere A. Probiotics and medical nutrition therapy. Nutr Clin Care 2004;7:56-68.
10. Fedorak RN, Madsen KL. Probiotics and the management of inflammatory bowel disease. Inflamm Bowel Dis 2004;10:286-99.
11. Goossens D, Jonkers D, Stobberingh E, van den Bogaard A, Russel M, Stockbrugger R. Probiotics in gastroenterology: indications and future perspectives. Scand J Gastroenterol Suppl 2003;15-23.
12. Calder PC. Polyunsaturated fatty acids, inflammatory processes and inflammatory bowel diseases. Mol Nutr Food Res 2008;52:885-97.
13. Razack R, Seidner DL. Nutrition in inflammatory bowel disease. Curr Opin Gastroenterol 2007;23:400-5.
14. Camuesco D, Comalada M, Concha A et al. Intestinal anti-inflammatory activity of combined quercitrin and dietary olive oil supplemented with fish oil, rich in EPA and DHA (n-3) polyunsaturated fatty acids, in rats with DSS-induced colitis. Clin Nutr 2006;25:466-76.
15. Seidner DL, Lashner BA, Brzezinski A et al. An oral supplement enriched with fish oil, soluble fiber, and antioxidants for corticosteroid sparing in ulcerative colitis: a randomized, controlled trial. Clin Gastroenterol Hepatol 2005;3:358-69.
16. Ishihara T, Tanaka K, Tasaka Y et al. Therapeutic effect of lecithinized superoxide dismutase against colitis. J Pharmacol Exp Ther 2009;328:152-64.

Chronic bronchitis doesn't affect just the lungs, but the heart and kidneys too

Chronic bronchitis (CB) is a case of upper respiratory inflammation that is almost exclusively caused by smoking (1). In fact, non-smokers don't get CB even after long-term inhalation of industrial pollutants, but those pollutants might just exacerbate existing CB in smokers (1).

You'd think at first that this was just a lung disease. But when you've had CB for awhile, poor breathing can produce hypoxemia and hypercapnia, which can trigger a pulmonary vasoconstriction reflex that increases the right heart's workload (1).

And chronic hypoxemia can do further damage. It will also increase secresion from the kidneys of erythropoietin (1). This, causes the bone marrow to increase red blood cells (which is why you can test for CB using a hematocrit assay) (1). The high red blood cell count make your blood flow like maple syrup, which can cause possible thrombosis (1).

Reference List

1. Nowak TJ, Handford AG. Pathophysiology: Concepts and Applications for Health Professionals. New York: McGraw-Hill, 2004, p318.

If you smoke, then it sucks (and blows) to be you

Most obstructive lung diseases are associated with smoking including pulmonary emphysema (PE) (1). Smoking affects pathogenesis of pulmonary emphysema by exaggerating destruction of alveolar septa (1).

The septa is linked to alpha1-antitrypsin (a1-AT), which is a plasma constitutent that antagonizes action of serine elastase (1). The enzyme degrades elastic tissue in walls of alveoli and is releaseed in the lungs in response to injury by minor infection or inhaled irritant (1). The smoke blocks action of a1-AT causing damage that draws phagocytes to the lungs and their excess release of serine elastase to degrade elastic tissue in walls (1).

PE is the condition that occurs when this disordered process destroys so much septa that the lungs'airways enlarge abnormally beyond terminal bronchioles (1). As septa continues to be distroyed, airways merge to form even larger sacs (1). A bulla is formed when air spaces enlarge to diameters above 1 cm (1). Without the septa, there is less surface area for gas exchange and less connective tissue that drive recoil of the lungs for inhalation (1). The less surface area is worsened by obstructive effects that occur as alveolar walls are destroyed, which can cause airways to collapse (1). Thus, not only is sucking air in more difficult, but breathing out is tough too (1).

Reference List

1) Nowak TJ, Handford AG. Pathophysiology: Concepts and Applications for Health Professionals. New York: McGraw-Hill, 2004, p318-320.

Why I couldn't be a doctor - primary or neurogenic shock

I faint at the sight of blood. It's extremely inconvenient when one of my kids decides to scrape a knee and needs a band-aid. In fact, just talking about blood makes me feel a bit weezy. Although my Pathophys class is, I think, a good cure for this problem.

My fainting is a result of primary shock, or neurogenic shock, which is caused by rapidly falling blood pressure and loss of consciousness. This happens, not because I'm losing blood like in hypovalemic shock, but because my brain is telling my nervous system to dilate blood vessels. It's important to point out that vasodilation creates a situation of relative hypovolemia. Unlike hypovolemic shock where blood is actually lost, in vascular shock the decrease in blood pressure happens because blood volume doesn't adequately fill the enlarged vascular space. Less blood gets to the heart and cardiac output can fall reducing pressure still.

Primary shock can be triggered by emotional trauma, intense pain or a vividly threatening experience like the color blood red. And basically what my body does by fainting is try to save me by knocking me senseless.

By doing so, the emotional stimulus to my autonomic centers that control my heart and vessel activity is effectively interrupted. My unconsciousness allows cardiac output and vasoconstriction is normalize.

Reference List

Nowak TJ, Handford AG. Pathophysiology: Concepts and Applications for Health Professionals. New York: McGraw-Hill, 2004, p295.

Diabetes link to depression

Research appears to suggest that there are two links established between diabetes and depression:

• diabetes as the potential cause for depression because of unbalanced hormones (1)
• depression as cause or worsening of diabetes because of cortisol (1)

Sounds like an awful downward spiral.

However, according to the American Diabetes Association, while daily stress of diabetes can cause frustration and depression, there are diabetes symptoms that may only appear to be those of depression (2). It would be important to distinguish which is what before treatment. Examples of possible symptoms mistaken to be a signs of depression are feelings of anxiety or lack of energy since these symptoms can easily be caused by high or low blood sugar (2).

Reference List

1. "Depression and Diabetes." Blue Cross and Blue Shield. http://www.ahealthyme.com/topic/depdiabetes."

2. American Diabetes Association. "Depression." Available at: http://www.diabetes.org/type-2-diabetes/depression.jsp

"Classic" versus "modified" carb loading

In the 1960s Scandinavian scientists researched carb loading and found you could doulbe glycogen stores by doing the following (1p270):

• Two sessions of intense exercise to exhaustion to deplete glycogen
• Two days of less than 10 percent carbs to effectively "starve" muscle
• Three days of rest while taking in 90 percent or more carbs

While certainly effective, this"classical" version of carb loading does have drawbacks. The low-carb sesssions leave you suffering from irritability and dizziness and you lose good training (1p270).

But modern research has proven that runners can reap benefits of carb loading while avoiding adverse effects (1p270):

1. Perform reduced intensity training for five days followed by resting one day.
2. Take in 50 percent carbs for first three days.
3. Take in 70 percent carbs for next three days.

The modified version has shown to increase glycogen stores 20-40 percent, effectively increasing performance just as well as the classical version.

Reference List

1. Gropper SS, Smith JL, Groff JL. Advanced Nutrition and Human Metabolism. Belmont, CA: Thomson Wadsworth, 2009.

When gramps has hypoglycemia

Growing up, whenever I visited my grandpa's place, he had snacks all around the house. I remember that he ate all day, but never ate a full dinner. And here's why: The human body runs on carbohydrates as its main fuel, thus, carbs are our primary macronutrients (1p105). Glucose is the most important carbohydrate because of its direct involvement in signaling insulin, its uptake into muscles and in glycolysis providing energy (1p105).

If concentrations of glucose are below normal, the body is hypoglycemic (1p105). To be precise, three criteria determine a disorder of true hypoglycemia: low serum glucose level, presence of andrenergic or neuroglucopenic symptoms, and relief of symptoms when eating a meal with carbohydrates that return serum glucose to normal levels (1p105). What if a person has low serum glucose, but no other symptoms (1p105)? Or what if a person has adrenergic or neuroglucopenic symptoms, but normal glucose levels (1p105)? Well, it's complicated (1p105). Neither are true hypoglycemia (1p105).

Two types of true hypoglycemia disorders exist: fasting hypoglycemia and fed (reactive) hypoglycemia (1p105). The first is typically caused by drugs like exogenous insulin used to treat type 1 diabetes, sulfonylureas, which stimulate insulin secretion, an insulinoma, or intake of excessive alcohol (1p105). The second is caused when patients have impaired glucose tolerance or idiopathic postprandial syndrome (1p105). In these cases, post-prandial insulin response may be delayed, followed by an excessive insulin release that drives glucose down too far (1p105).

My grandpa had fed (reactive) hypoglycemia. He was good about his treatment with diet therapy and, as appropriate, he avoided simple and refined sugars and tried to eat frequent and small snacks with mixed proteins, carbs and fats (1p105). Still, my personal belief is that he could've done a little better. The easy $1 Burger King Whopper got the best of him and we lost grandpa a few years back to coronary artery disease.

Reference List

1. Gropper SS, Smith JL, Groff JL. Advanced Nutrition and Human Metabolism. Belmont, CA: Thomson Wadsworth, 2009.

Running on Glucagon

I happen to be 30-year-old healthy male who can’t say has trained for a marathon, but if I were then I’d train to build up glycogen in my liver and muscle (1p269). I do this through regular endurance training (1p269) and eating enough carbs to stimulate glycogen synthesis (1p99). Glycogen synthesis happens when plenty of glucose 6-phosphate causes insulin to keep my blood glucose low and the glycogen is stored as a starch for later use (1p99). Liver glycogen, 7 percent of the weight of the liver, helps maintain my blood glucose, and muscle glycogen, 75 percent of total, would be my primary energy source when I start running (1p78). That glycogen is broken down to glucose units by a process of cleaving glycosidic bonds using phosphorolysis called glycogenolysis (1p80). To my body’s inconvenience, however, my glycogen stores are used up after an overnight fast of approximately 12-18 hours (1p256). Glycogenolysis in my muscle and liver will have depleted most if not all my glycogen to give my tissues fuel (1p256)! And I’m a heavy sleeper, so I’d be an early fasting state (1p257).

Glucagon is the hormone that will drive pathways at such a point (1p101). Glucagon kicks in hepatic gluconeogenesis breaking down amino acids from muscle to maintain my plasma glucose (p258), by recycling available lactate provided by red blood cells and muscle, and alanine (turned to pyruvate) from muscle cells, as well as glycerols from lypolysis (1p257;269). If I’m running a morning after a fast, what does my body have to do? My liver may be able to settle with fatty acids from my adipose tissue (although in my case of being too thin, there isn’t too much to go around for beta-oxidation), but my muscles and brain would really want that glucose (1p256;267). Glycolysis would degrade the glucose to pyruvate and, if under aerobic conditions, the pyruvate would be transported to the mitochondria into the TCA cycle; anaerobic conditions owould leave pyruvate converted to lactate (1p82).

Because I’m training as an endurance athlete, I’ d be running short aerobic cycles of 15-minute runs with an exertion below 60 percent VO(2) max and during this time my total fat oxidation would increase attributed to oxidation of muscle triacylglycerols (1p268). Fatty acids would be preferred for any exertion below 50 percent Vo(2) max) (1p269). But with a few, repeated supramaximal sprint bursts and increased exertion to 60-75 percent VO(2) max, then fat can’t be oxidized fast enough and my muscles would have to rely on carbohydrate oxidation (1p268). This is because fatty acids have only two oxygen molecules, not like carbohydrates, which have equal number of oxygen to carbon molecules (1p269). The lack of glycogen can be offset by my body’s acceleration of gluconeogenesis, but without new supply of ingested glucose, then muscle fatigue would set in accompanied by increased lactic acid in the blood due to inadequate oxygen to completely oxidize pyruvate to C02 and H2O (1p269).

To help avoid fatigue, I would be smart to take advantage of eating foods with low-glycemic index carbs before the event as well as an isotonic or hypotonic beverage with a supply of glucose (not slow-absorbing fructose) about 15-20 minutes before training (1p272). After training, I’m free to drink plenty of water and high-glycemic foods to replace glycogen (1p272). A few apples or orange wedges would do the trick (1p272).

Reference List

1. Gropper SS, Smith JL, Groff JL. Advanced Nutrition and Human Metabolism. Belmont, CA: Thomson Wadsworth, 2009.

You may be right handed, but we're all left hearted

Just as writing with my right hand eventually makes it hurt, while my left hand enjoys a relative stress-free life, my heart's left ventrical does much more work and is more stressed than my heart's right ventrical.

Because of the demand on the left heart, it also is larger, consumes more oxygen and is more vulnerable to oxygen imbalance. The lungs empty into the left heart so if it's not functioning to par, its possible it is unable to deliver blood to the circulation in the body. In addition to causing cerebral hypoxia, compromised systemic circulation decreases perfusion of kidneys activating the renin-angiotensin-aldosterone system. Angiotensin II increases peripheral resistance putting more strain on the left heart.

In most cases of heart failure, the left heart fails first. The right heart follows. But it is possible for the right heart to fail independently in primary lung diseases when pressure load on the right heart increases significantly.

Independent right-side heart failure can occur when there is resistance in the lung's vascular bed. The congestion of capillary beds include hepatomegaly and splenomegaly. Congestion of kidneys can decrease perfusion more than as would occur in left heart failure, resulting in increased fluid retention, edema, accumulation of impurities and waste. In time, the left heart will follow.

Reference List

Nowak TJ, Handford AG. Pathophysiology: Concepts and Applications for Health Professionals. New York: McGraw-Hill, 2004, p255.

Viral myocarditis

Myocarditis occurs as an inflammatory state of the myocardium. The most common kind is caused by a virus resulting in viral myocarditis, affecting usually young men and infants. The viral form is usually restricted to the heart and is most often caused by Coxsackie virus. It's usuallly a mild disease with pericardial pain, weakness and fatigue, but immune-suppression can lead to more serious symptoms including possible acute heart failure. Fetuses and newborns are most vulnerable.

Reference List
1. Nowak TJ, Handford AG. Pathophysiology: Concepts and Applications for Health Professionals. New York: McGraw-Hill, 2004.

How to avoid AGE-ing

Hyperglycemia causes yet more complications on cells because it increases formation of advanced glycation end (AGE) products (1-5). AGE products are formed by non-enzymatic reactions between reducing sugars and proteins, lipoproteins and nucleic acids and, in consequence, increase susceptibility to oxidative stress (1-5).

These AGE products are thought to accelerate “vascular cell aging” resulting in cardiovascular disease (1) , “brain aging” resulting in cognitive dysfunction and dementia (2). For these reasons, strong glycemic control may be valuable treatment (4).

Reference List
1. Orasanu G, Plutzky J. The pathologic continuum of diabetic vascular disease. J Am Coll Cardiol 2009;53:S35-S42.
2. Roriz-Filho S, Sa-Roriz TM, Rosset I et al. (Pre)diabetes, brain aging, and cognition. Biochim Biophys Acta 2008.
3. Piwowar A, Knapik-Kordecka M, Szczecinska J, Warwas M. Plasma glycooxidation protein products in type 2 diabetic patients with nephropathy. Diabetes Metab Res Rev 2008;24:549-53.
4. Nogueira-Machado JA, Chaves MM. From hyperglycemia to AGE-RAGE interaction on the cell surface: a dangerous metabolic route for diabetic patients. Expert Opin Ther Targets 2008;12:871-82.
5. Gasser A, Forbes JM. Advanced glycation: implications in tissue damage and disease. Protein Pept Lett 2008;15:385-91.

Why Type 1 diabetics need insulin injections

Type 1 diabetics require insulin injections because of failure of beta-cells of the pancrease to produce and secrete insulin (1). Thus, insulin injections play a vital role for being sure glucose metabolism is regulated and, effectively, lowering blood glucose (1). The insulin increases glucose oxidation, glycogen deposition, lipogenesis, protein synthesis and cell replication (1).

Insulin's absence causes uncontrolled catabolic hormones causing aberrations in metabolism of carbohydrates, fat and protein (1). Reduced glucose cellular uptake in muscle and adipose tissue cells severely affects them. The ultimate response on the body can be more violent than fasting or starvation (1). Hyperglycemia increases hepatic glucose output causes an osmotic diuresis and the water lost compounded by hyperpnea of acidosis, which could lead to dehydration (1).

Dehydration can lead to circulatory failure due to hemoconcentration via hypoxia shifting tissues to anaerobic metabolism (1). The situation causes acidosis to worsen due to higher concentration of lactic acid in the blood (1). Sodium is lost in diuresis caused by the ketonuria and glucosuria (1). Potassium is lost accompanying catabolism of protein and dehydration (1). Thus, not only are muscles and adipose tissue starved, but the resulting circulatory failure and hypotension could lead to low cerebral and renal blood flow (1). Ultimately, coma and death could follow (1).

Reference List
1. Gropper SS, Smith JL, Groff JL. Advanced Nutrition and Human Metabolism. Belmont, CA: Thomson Wadsworth, 2009, p277.

What's so important about glucose 6-phosphate anyway?

When your cells are in a low-energy state, they are hungry.

• Free glucose is converted to glucose 6-phosphate (G6P) by hexokinase/glucokinase (1). The reaction requires an investment of 1 ATP molecule, but effectively traps glucose within the cell (1).
• Glycogen is broken down to G1P and subsequently G6P (2p80-81). The G6P can then be used in metabolic pathways or, in the liver and kidneys, be converted back to glucose (2p80-81).
• In a hypoglycemic state, G6P can also formed from gluconeogenesis from non-carbohydrate sources (2p98).

G6P can then enter glycolysis to produce ATP or, if biosynthesis is needed, the hexomonophosphate shunt to produce NADP for fatty acid synthesis (2p84;95).

In a high-energy state (when cells are not hungry), G6P plays a role in the following.

• G6P negatively modulates the hexokinase/glucokinase reaction (2p84).
• G6P enters glycogenesis producing glycogen for storage of glucose (2p99). Glucose is now believed to enter glycogenesis via gluconeogenesis, first converting to lactate, taken up by the liver and converted to G6P (2p99).

Reference List

1.Dennison KJ, Topping J, Caret RL. General, Organic, and Biochemistry. New York: McGraw-Hill, 2007.
2.Gropper SS, Smith JL, Groff JL. Advanced Nutrition and Human Metabolism. Belmont, CA: Thomson Wadsworth, 2009.

Note: Here's a neat animation: http://www.science.smith.edu/departments/Biology/Bio231/