Ординатура / Офтальмология / Английские материалы / Clinical Medicine in Optometric Practice_Muchnick_2007

SYMPTOMS OF GASTROINTESTINAL DISEASE

Dysphagia

When a patient has difficulty swallowing, he or she often describes a “sticking” sensation that occurs when food passes through the throat. Often the patient will feel a sensation of a throat obstruction. A complete throat obstruction produces the inability to swallow, or aphagia. Dysphagia may be produced by stroke, toxins, Sjögren’s syndrome, myasthenia gravis, tumors of the throat, enlarged thyroid gland, a large-sized bolus of food, or inflammation of the throat structures.

myocardial infarction (MI), gastrointestinal (GI) obstructions, and intracranial masses and hemorrhage.

Gastrointestinal Reflux Disease

Gastrointestinal reflux disease (GERD) is so common that is has been reported to occur in 40% of Americans at least once monthly. During a bout of GERD, acid refluxed from the stomach bathes the esophagus and causes a burning sensation. In 5% of cases, esophageal ulcers result from the chronic, recurrent exposure to GI acid. The typical symptom of GERD is heartburn, in which a patient feels a substernal warming that extends to the throat.

Nausea and Vomiting

Vomiting, or emesis, is the uncontrollable oral expulsion of contents from the upper intestine and stomach. Vomiting is often preceded by nausea and the urge to vomit. Nausea and vomiting are caused by factors that include drugs, surgery, toxins, inflammations, motion sickness, psychiatric disorders, infections and reflux,

Diarrhea

More than a billion people worldwide suffer at least one bout of diarrhea per year. Every year 50 million people in the United States must restrict activities because of acute diarrhea. Eight million children die worldwide each year from chronic diarrhea. Diarrhea results in watery, unformed feces passing quickly through the GI

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tract. Causes of acute diarrhea lasting less than 2 weeks include infections, Reiter’s syndrome, medications, and psychogenic factors. Chronic diarrhea lasting longer than 4 weeks may be caused by medications, surgery, hormonal changes, bacterial infections, lactose intolerance, inflammatory bowel disease (IBD), Crohn’s chronic ulcerative colitis, radiation treatment, and psychogenic factors.

Colon

Diarrhea, pain, blood in the feces, and constipation are typical symptoms and signs arising from colon disorders. Such procedures as colonoscopy, sigmoidoscopy, barium enema, and stool culture are used to study the colon.

Weight Loss

Unintentional weight loss in an otherwise healthy patient may be an early sign of a serious underlying condition. In the elderly, weight loss is often the result of depression, although cancer and IBD should be excluded. Besides cancer, other causes of weight loss include anemia, arthritis, infections, medications, stroke, eating disorders, alcoholism, renal insufficiency, malabsorption syndrome, and emphysema and COPD.

Gastrointestinal Bleeding

Bleeding from the GI tract may occur from the mouth (hematemesis) or the rectum (hematochezia). The blood may be bright red or black. If the bleeding is detected only by laboratory testing it is referred to as occult GI bleeding (GIB). GIB can cause syncope, lightheadedness, and difficulty breathing. The most common cause of an upper GI bleed is ulcer, followed by varices and, in rare cases, malignancy. Lower GI bleeds (LGIB), when intestinal, are most often the result of tumors such as lymphomas and the use of NSAID medications.

ANATOMICAL CORRELATION

OF GASTROINTESTINAL SYMPTOMS Esophagus

Heartburn and dysphagia, or difficulty in swallowing, both often arise from esophageal problems. These conditions are usually investigated with esophagoscopy, the technique of visualizing the esophagus.

Stomach

The symptoms and signs of nausea, vomiting, and epigastric pain often arise from stomach ailments. The stomach is evaluated by an upper GI x-ray series and gastroscopy.

Small Intestine

Pain, nausea, vomiting, and diarrhea are typical symptoms arising from small intestine disorders. This is investigated by techniques such as duodenoscopy, kidney-ureter-bladder x-ray series, CT, stool cultures, and colonoscopy.

Anus/Rectum

The anus/rectum produces symptoms including pain, pruritus, constipation, and incontinence. This area is evaluated by sigmoidoscopy.

SIGNIFICANT GASTROINTESTINAL DISEASES

Peptic Ulcer Disease

An ulcer consists of an inflammatory defect in the mucosal wall of the stomach or duodenum. Ulcers produce a chronic excavation of the gastric epithelial mucus lining that causes epigastric pain made worse by fasting and better by eating. The majority of gastric ulcers are associated with Helicobacter pylori infection and NSAID use, although malignancy is a possibility. Treatment for peptic ulcer disease (PUD) includes the eradication of H. pylori infection and the prevention of NSAID-related ulcer formation. Antacid use also helps to treat acid peptic disease. Surgical approaches exist that are designed to decrease acid production.

Absorption Disorders

Absorption disorders almost invariably cause a reduced absorption of a necessary compound and are therefore often referred to as malabsorption syndromes. The most common symptom of absorption disorders is diarrhea. If dietary fat is not absorbed well, the condition is referred to as steatorrhea. For example, the inability to absorb lipids, which may be the result of pancreatitis, produces weight loss and vitamin deficiency. An example of the malabsorption of carbohydrates is lactose intolerance, in which the disaccharide present in milk cannot be broken down for digestion, producing cramps, diarrhea, intestinal pain, and flatulence.

Whipple’s Disease

This multisystem condition is caused by the bacteria Tropheryma whippelii. Characteristics of this chronic disease include joint pain, heart problems, weight loss, diarrhea, and steatorrhea. This disorder is suspected in middle-aged Caucasian men with an insidious onset of fever, diarrhea, and abdominal and joint pain. Whipple’s disease can cause pericarditis and chronic aortic regurgitation and may lead to congestive heart

failure. Ocular signs include bilateral, posterior uveitis, supranuclear palsy with upgaze paresis, papilledema, and cranial nerve III, IV and VI palsies. It is treated with a prolonged regimen of antibiotics including penicillin or trimethoprim.

Vitamin Deficiency

Malabsorption may cause a deficiency in the fatsoluble vitamins (A, D, E, and K) and the water-soluble B vitamins. Pancreatic, liver, and intestinal disorders (such as Whipple’s disease and Crohn’s disease [CD]) can all cause malabsorption of vitamins.

VITAMIN A

Known as retinol and the chemically related retinoids, vitamin A is essential for normal vision, cell growth and cell differentiation, humoral immunity, and phagocytosis. Approximately 80% of all vitamin A found in the body is absorbed from food, and approximately half of this amount is held in reserve in the liver. The remaining portion of ingested vitamin A is excreted in the urine or bile. The liver intermittently excretes vitamin A in the form of retinol bound to a specific protein. Through a complex chemical reaction, vitamin A then enters the cell to be used as transporting agents and enzyme reaction enablers. These elements function to control cell proliferation and differentiation. In the eyes, a form of vitamin A known as retinaldehyde acts as a visual pigment to help capture light and produces a nerve impulse that causes a visual response.

Dietary sources of vitamin A include eggs, butter, cheese, fish, liver, dark-green leafy vegetables, and dark-colored fruits. Poor sources of vitamin A include mother’s milk, cow’s milk, rice and wheat. Vitamin A deficiency can lead to blindness and death. Patients with vitamin A deficiency may develop skin lesions, night blindness, dry-eye syndrome (Figure 11-1), and xerosis. White patches of keratinized epithelium may

FIGURE 11-1 ■ Dry eye with superficial punctuate staining.

form on the sclera and are known as Bitot’s spots. Eventually the cornea may ulcerate, causing perforation and permanent corneal scarring. Xerophthalmia, a condition characterized by the sloughing of the corneal epithelium, prevents corneal wound healing and is aggravated by the dry eye condition. In extreme cases of avitaminosis A, the conjunctiva shrinks and scars, and abnormal adhesions develop on the eyelid. This condition is known as cicatricial pemphigoid and results in adhesions of the palpebral conjunctiva to the bulbar conjunctiva (Figure 11-2).

Vitamin A deficiency may be detected by blood testing of the serum retinol level. Treatment of vitamin A deficiency includes an intramuscular injection of 100,000 units of vitamin A, or 200,000 IU of vitamin A by mouth. This is followed by 200,000 IU of vitamin A orally every 6 months.

In adults, the daily intake of vitamin A should not exceed 10,000 IU. Overdosage of vitamin A can lead to toxicity and result in vertigo, diplopia, seizures, and increased intracranial pressure. Vitamin A toxicity may occur in adults who ingest 50,000 IU of vitamin A on a daily basis for several months. Symptoms include headache, dry skin, vomiting, diarrhea, and lymph node swelling. Optometrists should be aware of the potential of pseudotumor cerebri in vitamin A toxicity, and screen all patients with papilledema for possible vitamin A overdosage.

VITAMIN D

Vitamin D is a hormone produced in the skin by exposure to sunlight. Dietary sources of vitamin D are not necessary as long as adequate sunlight reaches the skin. The two forms of vitamin D interact with parathyroid hormone to regulate calcium and phosphate levels in the bone, small intestine, and kidney.

A deficiency of vitamin D causes rickets, wherein there is mineralization of the skeletal matrix. The

FIGURE 11-2 ■ Symblepharon: Adhesions of the palpebral to the bulbar conjunctiva.

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growing bones in children with rickets undergo bowing, stunting, and fractures. Treatment of rickets includes sun exposure, oral vitamin D (800 IU daily for 6 weeks followed by daily 200 IU supplements) and monitoring for bone healing during a 6-month period.

Overdosage of vitamin D may occur with an intake as low as 1800 IU per day. Symptoms of vitamin D toxicity include fatigue, headache, nausea, vomiting, and diarrhea. Areas of calcification may occur throughout the body. Vitamin D toxicity may cause optic atrophy in infants because of hypercalcemia. Calcium deposits in and around the optic foramina create a narrowing of the opening that leads to pressure on the optic nerve. Band keratopathy may be produced in cases of hypervitaminosis D (Figure 11-3).

VITAMIN E

Vitamin E is a potent antioxidant radical scavenger and thus protects cellular structures from harmful free radical oxidation. Vitamin E also acts as an antiinflammatory by inhibiting prostaglandin synthesis. Approximately half of the vitamin E that is ingested is absorbed and transported to the liver. In the liver, vitamin E binds to lipoproteins to become widely distributed throughout all tissues in the body. Most of the vitamin E is then stored in muscle and fat, and the remainder is excreted in feces and urine. Dietary sources of vitamin E include meat, nuts, grains, and vegetable oils.

No known deficiency of vitamin E exists, but a toxic dose of greater than 800 mg/d may reduce platelet aggregation and so is contraindicated in patients taking blood-thinning agents.

VITAMIN K

The two forms of vitamin K are found in meat and vegetables (vitamin K1) and synthesized by bacterial flora (vitamin K2). Vitamin K plays a significant role

FIGURE 11-3 ■ Band keratopathy. Calcium deposits in the cornea in hypervitaminosis D.

in blood coagulation and a deficiency results in bleeding problems. High doses of vitamin K can impair the actions of oral anticoagulants and result in blood coagulation and increase the risk of stroke. Vitamin K toxicity may occur if too much is absorbed from a diet high in dark-green leafy vegetables, such as might be prescribed to patients with age-related macular degeneration (ARMD). Therefore ARMD patients placed on blood thinners such as Coumadin should be warned about the risks of eating a diet rich in vitamin A, and limit items such as dark-green leafy vegetables, olive oil, butter, margarine, liver, milk, beef, and coffee. In these cases, the risks of blood clotting because of high levels of vitamin K may outweigh the benefits of stabilizing the macular degeneration condition.

VITAMIN B1

Thiamine is a coenzyme used for cleavage of carboncarbon bonds. This nutrient also aids in the metabolism of carbohydrates and amino acids. Vitamin B1 may aid in peripheral nerve conduction. B1 is stored in the brain, heart, liver, kidneys and muscle tissue. Thiamine is transported through the body bound to plasma proteins and red blood cells. It is found in yeast, pork, beef, grains and nuts. This vitamin is reduced in the body by the consumption of rice, coffee, and tea.

A deficiency of vitamin B1 results in anorexia, apathy, and weakness. Eventually heart problems may occur, including tachycardia and congestive heart failure, known as beriberi. Wernicke’s encephalopathy occurs because of vitamin B1 deficiency associated with alcoholism, and is characterized by horizontal nystagmus, ophthalmoplegia, and mental impairment. Treatment includes the parenteral or oral delivery of thiamine.

VITAMIN B2

Riboflavin is a cofactor for oxidation reduction reactions. Important in the metabolism of fat, protein, and carbohydrate, vitamin B2 is primarily found in milk, eggs, fish, and broccoli. Ocular manifestations of vitamin B2 deficiency include reduced visual acuity secondary to cataract and keratoconjunctivitis sicca with subsequent corneal neovascularization. Angular cheilitis at the corners of the mouth represent infection in the folds of the skin because of vitamin B2 deficiency (Figure 11-4). Such deficiency may also lead to a loss of papillae on the tongue (Figure 11-5), known as a “smooth tongue.”

VITAMIN B3

Niacin is a coenzyme used in oxidation and reduction reactions. Niacin is further used in fatty acid and steroid biosynthesis and glycolysis and protein metabolism.

FIGURE 11-4 ■ Angular cheilitis (angular stomatitis). Infected folds of skin at corners of mouth caused by vitamin B2 deficiency. (From Mandell GE, Bennett JE, Dolin R: Principles and practice of infectious diseases, ed 6, Edinburgh, 2005, Churchill Livingstone.)

FIGURE 11-5 ■ Smooth tongue. This smooth, red, glossy appearance is caused by loss of papillae from anemias, vitamin deficiency, and malabsorption syndromes. (From Feldman M:

Sleisenger & Fordtran’s gastrointestinal and liver disease, ed 8, Philadelphia, 2006, Saunders.)

Niacin deficiency produces pellagra. This condition begins with a loss of appetite, weakness, stomach pain, and vomiting, and proceeds to skin rashes, diarrhea, depression, seizures, dementia, and death.

Niacin is used to treat hyperlipoproteinemias and acts to decrease blood cholesterol. In therapeutic doses, vitamin B3 may cause a classic “flushing” of the skin, a temporary reddening of the face.

VITAMIN B5

Pantothenic acid is a cofactor in energy metabolism, steroid hormone synthesis, and hemoglobin formation. This nutrient is found primarily in beef, cereal grains, and dark-green leafy vegetables.

VITAMIN B6

Pyridoxine is a cofactor for enzymes of amino acid metabolism, and is also involved in neurotransmitter synthesis. It is found in meat, nuts, and wheat bran. A deficiency may occur in patients taking isoniazid, oral contraceptives, L-dopa, and some antibiotics, and results in weakness, dermatitis, depression, confusion, and peripheral neuropathy.

VITAMIN B9

Folic acid has been shown to prevent disease and its prenatal supplementation prevents neural tube disorders. Found in nuts, fruit, liver, lentils, and leafy green vegetables, vitamin B9 has been suggested as a supplement in a “heart healthy” diet.

VITAMIN B12

Primary nutritional sources for this vitamin include meat, fish, liver, and kidneys. A deficiency of vitamin B12 results in anemia and neurologic signs.

BIOTIN

Biotin is a water-soluble vitamin that plays a role in gluconeogenesis and fatty acid synthesis. It also aids in the catabolism of amino acids such as leucine. It is found in liver, soy, beans, yeast, and egg yolks. A deficiency of biotin may result in mental changes including hallucinations and depression. A rash may appear around the eyes with such a deficiency, and treatment consists of oral doses of biotin.

VITAMIN C

Vitamin C participates in oxidation and reduction reactions and is a potent antioxidant. Vitamin C is important in connective tissue metabolism and drugmetabolizing tissue enzyme systems. This nutrient is biologically active in the synthesis of corticosteroids and the metabolism of cholesterol.

Vitamin C is found in citrus fruits, green vegetables, tomatoes, and potatoes. A deficiency of vitamin C produces scurvy, a condition characterized by joint pain, weakness, depression, bleeding of the skin and gums, and impaired bone growth in children. Avitaminosis C may yield hemorrhagic conjunctivitis (Figure 11-6). Treatment for scurvy includes vitamin C supplementation.

High-dose vitamin C supplementation has been shown to improve glycemic metabolism. Toxic levels of vitamin C (more than 2 g/day) may produce diarrhea and abdominal cramping.

Inflammatory Bowel Disease

This idiopathic and chronic intestinal inflammation is composed of ulcerative colitis (UC) and CD. IBD is found predominantly in the United States, England,

FIGURE 11-6 ■ Hemorrhagic conjunctivitis in vitamin C deficiency.

Norway, and Sweden. The disease occurs primarily in patients between 15 and 30 years. A slightly lower peak occurs in patients between 60 and 80 years of age.

Although the etiology of IBD is as yet unknown, it is hypothesized that in genetically predisposed individuals, infections, smoking, and a host of anatomical factors conspire to cause a chronic activation of the mucosal immune system. IBD appears to be an inappropriate response to these various stimuli. The immune inflammatory response in IBD is perpetuated by T-cell activation. Then, a cascade of inflammatory mediators acts to prolong the response and produces a chronic condition. This inflammatory response results in characteristic small ulcerations and erythema of the colon (Figure 11-7).

Skin findings in IBD include erythema nodosum (Figure 11-8) and pyoderma gangrenosum (Figure 11-9).

Between 1% and 10% of patients with IBD have an associated ocular condition. The most common are conjunctivitis, anterior uveitis, and episcleritis (Figure 11-10). Anterior uveitis is particularly associated with CD, and can produce pain, photophobia, and blurred vision, but can also produce a “silent” uveitis found

FIGURE 11-8 ■ Erythema nodosum. Bright, red, raised, tender lesions, usually in the front of the shins. (From Habif TB:

Clinical dermatology: a color guide to diagnosis and therapy, ed 4, St. Louis, 2004, Mosby.)

only on slit-lamp evaluation. Prompt treatment with topical cycloplegic and corticosteroid preparations minimizes scar-tissue formation in these cases of IBDrelated anterior uveitis.

Ulcerative Colitis

UC is a form of IBD that causes the mucosa of the rectum and colon to become granular, hemorrhagic, edematous, and ulcerated. This process can produce polyps when the epithelium regenerates. A chronic state of UC produces a colon that is atrophic, narrowed, thin, and ulcerated to the point of perforation. Symptoms of UC include diarrhea, rectal bleeding,

FIGURE 11-9 ■ Pyoderma gangrenosum. An advancing crusted edge with irregular exudative ulceration and central healing with scarring, that is associated with ulcerative colitis. (From Feldman M: Sleisenger & Fordtran’s gastrointestinal and liver disease, ed 8, Philadelphia, 2006, Saunders.)

FIGURE 11-10 ■ Episcleritis associated with Crohn’s disease.

and abdominal pain. Bleeding may occur mixed with the stool. Laboratory testing reveals an elevated C-reactive protein and erythrocyte sedimentation rate (ESR). Sigmoidoscopy may be used to assess the state of the disease. A barium enema is helpful in making the diagnosis of UC.

Mild-to-moderate UC is treated with sulfasalazine and other 5-ASA agents. These agents deliver antibiotic

and antiinflammatory therapy to the colon. Side effects of sulfasalazine are common, and include headache, anorexia, nausea, vomiting, and skin rash. Sulfa-free aminosalicylate preparations have been developed to reduce these unwanted side effects.

Moderate-to-severe UC is treated with glucocorticoids. These steroid preparations should be tapered as symptoms reduce. During periods of remission, steroids should not be used for maintenance therapy.

Antibiotics have not been shown to be effective in the treatment of UC.

Azathioprine is a purine analogue used in conjunction with glucocorticoids for the treatment of UC.

Crohn’s Disease

CD can affect all parts of the GI tract, from the mouth to the rectum. CD results in segmental inflammation with associated fistulas, fissures, abscesses, and ulcerations that penetrate deep into the mucus tissue. Resolution of these inflamed areas produces fibrosis and scarring of the bowel. Chronic, recurrent bowel obstructions result from this structuring of the bowel. CD is a granulomatous disease that results in noncaseating granulomas in all layers of the bowel wall, lymph nodes, liver and pancreas.

The symptoms and signs of CD include fever, diarrhea, a palpable mass, and right lower quadrant pain.

Laboratory testing may help differentiate CD from UC.

Mild-to-moderate CD is treated with 5-ASA, metronidazole, or ciprofloxacin, oral glucocorticoids, or azathioprine. Cyclosporin has a role in the treatment of severe CD. Maintenance therapy for CD includes methotrexate (MTX) to prevent exacerbation of the CD.

Anterior uveitis is associated with CD. Patients with CD must be monitored for uveitis at least twice yearly with a slit-lamp examination. Most commonly, the diagnosis of CD-related anterior uveitis is made in the optometrist’s office when cells are detected in the anterior chamber of a patient with known CD or with abdominal cramps. The uveitis may occur during periods of quiescence, although patients may notice red eyes associated with bouts of diarrhea and vomiting associated with CD exacerbations.

Behçet’s Disease

Behçet’s disease, an uncommon, multisystem nongranulomatous disease of unknown etiology, is characterized by GI symptoms, colitis, nonulcerative skin lesions, and uveitis. Its highest incidence is in the Far and Middle East.

Behçet’s disease presents as a triad of oral ulcers (Figure 11-11), genital ulcers (Figure 11-12), and ocular

FIGURE 11-11. ■ Oral ulcerations associated with Behçet’s syndrome. The condition presents with painful ulcers in the mouth and pharynx. (From Blodi FC: Ocular involvement in dermatologic disease. In Mausolf FA, ed: The eye and systemic disease, St. Louis, 1975, Mosby-Year Book.)

FIGURE 11-12 ■ Genital ulcerations associated with Behçet’s syndrome. Recurrent orogenital ulceration. (From Blodi FC: Ocular involvement in dermatologic disease. In Mausolf FA, ed: The eye and systemic disease, St. Louis, 1975, Mosby-Year Book).

FIGURE 11-13 ■ Hypopyon in a case of Behçet’s syndrome.

FIGURE 11-14 ■ Cells in the anterior chamber in Behçet’s syndrome.

inflammation. Much of the GI tract may become involved and even the joints may become inflamed. Treatment of Behçet’s disease includes systemic corticosteroids and azathioprine.

Ocular sequelae include hypopyon (Figure 11-13), uveitis (Figure 11-14), retinal vasculitis (Figure 11-15), cataract formation, and glaucoma.

FIGURE 11-15 ■ Central retinal vein occlusion in a case of Behçet’s syndrome.

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Endocrinology encompasses the action and secretion of hormones, the endocrine glands that produce these chemical messengers, and the regulation of physiological functions by means of feedback

mechanisms.

The anatomical basis of endocrinology is the multitude of glands dispersed throughout the body. This chapter discusses specific endocrine glands, including the thyroid gland, parathyroid glands, pituitary gland, adrenal cortex and pancreatic islets, and how derangements in their hormonal secretions cause physiological changes that ultimately affect the visual system.

Endocrine glands release hormones that regulate physiological processes throughout the body. Hormones produce a wide range of effects, including the control of blood pressure and vascular tone, the stimulation for blood production in the bone marrow and growth, the regulation of digestion and serum glucose, and a vast array of other biological functions. The brain itself controls the level of hormonal activity by release of its own hormones, and elegant feedback regulatory systems exist to maintain hormonal balance.

THE ROLE OF HORMONES

A hormone is a chemical produced and secreted by a gland that acts to set in motion cellular responses and physiological processes. Hormones may be synthe-

sized and then stored within granules under the plasma membrane of the gland. A stimulus, such as a neural signal or chemical-releasing factor, influences the secretory granule to merge with the plasma membrane, degranulate, and spill its hormonal contents into the bloodstream. Other hormones, such as steroids, may be synthesized and released directly into the bloodstream.

The level of a given hormone in the bloodstream is influenced by the half-life of the hormone and the rate of its secretion. In addition, most hormones circulate bound to blood proteins. By binding to a certain hormone, a serum protein prevents access to specific sites. In addition, protein binding extends hormonal influence by “pooling” the hormone, effectively increasing the hormone’s half-life.

Hormones gain access to specific organs by an interaction with a receptor site. The sites for hormone binding may be nuclear or on the cell membrane. Small molecular hormones such as thyrotropin-releasing hormone (TRH) bind to nuclear sites because they can diffuse across the cell membrane. Large proteins such as insulin bind to cell membrane receptor sites.

Once bound to a receptor site on a cell, the hormone acts to initiate specific biological responses. In most cases, these processes include reproduction, body growth, and maintenance of metabolism and homeostasis.

The maintenance of homeostasis is an impressive example of hormonal influence. All hormones impact