gout

A 55-year-old neighbor of mine was awakened in the wee hours of the morning recently with an excruciating pain in his right big toe that rendered him unable to walk. As happens in a classic attack of gout, the onset was sudden and the affected joint red and swollen.

Long regarded as a “disease of kings” for its association with a diet rich in meats and alcohol, gout in modern times has become a decidedly more plebeian disorder. More than six million adults in the United States have had it, and the numbers are rising steadily as the population ages, becomes heavier and is exposed to foods and other substances that can precipitate the disorder in susceptible people.

And while historically gout has been a male disease (three-fourths of cases occur in men), the incidence has been rising in older women, with as many as one in 20 over age 70 now afflicted.

Fortunately for my neighbor, the fiery pain in his toe subsided in a few days, and while he has no idea what brought on the attack, he said he’s now “eating more healthfully.” Unfortunately, although some people never experience a second attack, others can suffer recurrences several times a year.

Gout Causes and Risks

Recurrent attacks are more likely if the underlying cause of gout is not treated. That cause is a high blood level of uric acid that forms irritating urate crystals that lodge in joints or soft tissues, causing intense pain.

Uric acid is produced when the body metabolizes purines, common components of many foods, especially organ meats, anchovies, herring, asparagus and mushrooms. Other dietary contributors include excessive consumption of alcohol and possibly soft drinks containing fructose.

A study published in November in The Journal of the American Medical Association linked an increased intake of sugar-sweetened soda to a raised risk of gout in women, who until menopause are relatively protected against the disease by estrogen, which helps the body excrete uric acid.

Elevated levels of uric acid can result either from the body’s overproduction of the substance or, more commonly, from an inability of the kidneys to excrete it adequately. Dr. Tuhina Neogi, a rheumatologist at the Boston University School of Medicine, explained that humans lack the enzyme uricase, present in most other animals, and thus are unable to convert urate into allantoin, the soluble end-product of purine metabolism.

Dr. Neogi noted recently in The New England Journal of Medicine that simply having a high level of uric acid is not, by itself, enough to cause gout. “Other factors play a contributing role,” she said in an interview.

As sometimes happens, the treatment of one disease can cause another. Among the medications linked to an increase risk of developing gout are thiazide diuretics, the first line of drug treatment for high blood pressure; cyclosporine, an immunosuppressant drug used to prevent organ rejection in transplant patients; and low-dose aspirin, commonly taken to reduce the risk of heart attack and stroke. (On the other hand, aspirin in high doses — three or more grams a day — protects against gout by increasing uric acid excretion, Dr. Neogi wrote.

Even drugs used to lower uric acid levels long-term can initially provoke an attack of gout, presumably by mobilizing body stores of urate, she said.

The risk of gout is also higher among people with disorders that are increasingly common in modern society, including hypertension, diabetes, high cholesterol, atherosclerosis and congestive heart failure. Obesity and the so-called metabolic syndrome, which includes insulin resistance, are other common factors that can make an attack of gout more likely.

People with a family history of gout also are at greater risk of developing it. Several genes have been linked to the disease.

Diagnosis and Treatment

Dr. Neogi noted that people vary in their response to uric acid. High blood levels are not always present during an attack of gout, she said, and some people with high levels never develop the disease.

Although symptoms are usually quite characteristic — rapid development of severe pain, redness and swelling, most often in the first joint of the big toe — a more certain diagnosis requires detection of urate crystals in an inflamed joint during an attack or between attacks. As this involves drawing fluid from the affected joint, it is not often done in routine medical practice, she said.

Sometimes in older people, especially women, multiple joints can be involved, leading to a mistaken diagnosis of rheumatoid arthritis.

If gout is untreated and the disease becomes advanced, deposits of urate crystals may form into nodules called tophi beneath the skin. While usually not painful, tophi can become swollen and tender during flare-ups of gout. Urate deposits may also cause kidney stones.

In the beverage department, alcohol is best avoided (or limited to one drink a day, if that) and sugary soft drinks avoided altogether. They are nothing more than empty calories. Diet soda, however, is not a problem, at least not with regard to gout.

Caffeine appears to be protective; routine high intake of coffee (and perhaps also tea) can lower uric acid levels. Patients have also reported that cherry juice (or eating cherries or other dark-colored fruits, like purple grapes and blueberries) may be protective and prevent recurrences.

It is most helpful to drink lots of water throughout the day — one to two liters, plus another one to two liters of other liquids — to limit the buildup of urate and keep kidneys flushed.

In terms of medication, my neighbor did the right thing when his gout attack occurred. He took a hefty dose (800 milligrams) of ibuprofen, an over-the-counter nonsteroidal anti-inflammatory drug (Advil and Motrin are common brand names), to reduce the pain and inflammation in his affected joint.

Had he seen a doctor, he might have been prescribed colchicine, which is most effective if taken soon after gout symptoms develop. Unfortunately, this medication can cause side effects, like nausea, vomiting and diarrhea, that limit its usefulness.

If neither of these medications can be used, a corticosteroid like prednisone may be taken orally or injected into the affected joint to reduce pain and inflammation.

Patients who experience frequent attacks may require continuing treatment with urate-lowering drugs called xanthine oxidase inhibitors, like allopurinol and febuxostat, which reduce the amount of uric acid the body produces. Another drug, probenecid, helps the kidneys excrete uric acid.

AG ch-1

Pericardium is protective barrier around heart. Consider standing in a small closet, u begin to blow up a balloon, eventually balloon will stick to closet wall=parietal pericardium and also ballon will come back and stick to u=visceral pericardium. The intermitent space is filled with lubricants . If blood due to trauma or injury occurs in this space, heart has no place to expand=life threatening. Pericarditis=inflammation w/c may affect heart moving properly. Heart has 4 chambers, 2 atria, atrium=waiting room and 2 ventricles. Path= LV-> systemic-> rt atrium-rt venticle->lung-> left atrium-> LV. Valves are mitral, aortic tricuspid and pulmonary. Left side of heart is four times as thick b/c must pump throughout body while rt side just pumps to lungs. Aorta is vessel w/c comes off LV. Comes back and gives blood to heart via the rt and left coronary artery. Blockages=> infarction. Lots of hollow structures are joined= anastomosis=redundancy. Sinoatrial node is the primary pacemaker. Current spreads to the av node down through bundle of his to the purkinje fibres. If atrial fibrillates, cardiac out decreases to 70%. Can lead to clots. Heart has a natural rhythm. If infarction occurs on eletrical conduit ie sa node ->av node-> bundle of his->purkinje fibres. heart is autorhythmic hence will beat but at a faster rate and will be less efficient due to less co-operation from other parts of heart.

Diet Drug Orlistat Linked to Kidney, Pancreas Injuries

Why? From Dr. Arya M. Sharma blog
The cause of this potential side effect is related to the simple fact that the unabsorbed fat and bile acids resulting from the use of orlistat may react with calcium in the intestinal lumen, limiting the amount of free calcium binding with oxalate and thereby raising intestinal oxalate absorption leading to hyperoxaluria, which in turn can promote formation of oxalate stones.

This rather complex-sounding but rather straightforward state of affairs was first proposed based on a marked increase in urinary oxalate excretion observed in rats given orlistat together with a high-fat diet in a study by Renato Ribeiro Ferraz and colleagues from the Universidade Federal de São Paulo published in KIDNEY INTERNATIONAL in 2004.

In 2007, Ashutosh Singh and colleagues from the University of Tennessee described the case of a female patient with chronic kidney disease, who developed acute oxalate nephropathy with the use of orlistat (Am J Kidney Dis). Urine sediment showed abundant calcium oxalate crystals and 24-hour urine oxalate concentration was significantly elevated. Kidney biopsy showed deposition of calcium oxalate crystals within the tubular lumens. A repeat biopsy one month after discontinuing orlistat no longer showed signs of oxalate and renal function slowly recovered to baseline.

Now, in this month's issue of OBESITY, Kemal Sarica and colleagues from the Memorial Hospital in Istanbul, Turkey, report the data from a study in 95 obese patients (57 men, 38 women) randomly assigned to treatment with orlistat for 6 months vs. no specific medication. In the treatment group, two-thirds of patients showed a marked increase in urinary oxalate excretion at 3 months, which largely persisted at 6 months. Although no kidney stones were noted, the authors commented that the increase in oxalate excretion would have been enough to promote oxalate stone formation in susceptible individuals.