Advanced clinical chemistry

1 Phenylketonuria
(PKU) is an autosomal recessive metabolic genetic disorder characterized by a mutation in the gene for the hepatic enzyme phenylalanine hydroxylase (PAH), rendering it nonfunctional.[1]:541 This enzyme is necessary to metabolize the amino acid phenylalanine (Phe) to the amino acid tyrosine. When PAH activity is reduced, phenylalanine accumulates and is converted into phenylpyruvate (also known as phenylketone), which is detected in the urine.[2] Since its discovery, there have been many advances in its treatment. It can now be successfully managed by the patient under ongoing medical supervision to avoid the more serious side effects. If, however, the condition is left untreated, it can cause problems with brain development, leading to progressive mental retardation, brain damage, and seizures. Early cases of PKU were treated with a low-phenylalanine diet. More recent research has now shown that diet alone may not be enough to prevent the negative effects of elevated phenylalanine levels. Optimal treatment involves maintaining blood Phe levels in a safe range while monitoring diet and cognitive development. There is no cure for PKU, but patients who are diagnosed early and maintain a strict diet can have a normal life span with normal mental development. Phenylketonuria can now be detected during the first few days of life by two reliable mass screening techniques; and its major consequence, severe mental retardation, can be prevented by the early institution of a low phenylalanine diet. Case finding, based on determination of phenylalanine serum levels in newborns before discharge from the hospital, appears to yield an acceptable number of new cases without excessive numbers of false positive or false negative tests at the 4 mg per 100 ml reporting level. Feeding history does not appear to be a major factor in influencing test results. In addition to finding cases of phenylketonuria, newborn blood screening has called attention to another group of infants with hyperphenylalaninemia of other causes. The differential diagnosis in such cases is important because the restrictive diet necessary for patients with phenylketonuria might be harmful to others. Such factors as enzymatic immaturity, heterozygote carriers, maternal enzymatic capacities and other amino-acidemic states must be ruled out by thorough examination. Careful observation, investigation and reporting of experience with these patients will help to eliminate some of the present deficiencies in the knowledge of normal and abnormal amino acid metabolism. 2

Aminoaciduria

Aminoaciduria is the presence of amino acids in the urine. Small amounts of amino acids are also present in normal urine. Increased total urine amino acids may result from metabolic disorders, chronic liver disease or renal disorders. Aminoacidurias can be divided into primary and secondary aminoacidurias.

Abnormal clinical and laboratory findings for urine / Urine test / urination disorder (R80R82, 791)
Red blood cells White blood cells Proteinuria Small molecules Pathogens Hematuria (Microscopic hematuria) Eosinophiluria Albuminuria/Microalbuminuria Myoglobinuria Hemoglobinuria Glycosuria Ketonuria Bilirubinuria Hyperuricosuria/Hypouricosuria Aminoaciduria Bacteriuria

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Other Chyluria Crystalluria osmolality (Isosthenuria Hypersthenuria)

3 Ketonuria
is a medical condition in which ketone bodies are present in the urine. It is seen in conditions in which the body produces excess ketones as an alternative source of energy. It is seen during starvation or more commonly in type I diabetes mellitus. Production of ketone bodies is a normal response to a shortage of glucose, meant to provide an alternate source of fuel from fatty acids.

Pathophysiology
Ketones are metabolic end-products of fatty acid metabolism. In healthy individuals, ketones are formed in the liver and are completely metabolized so that only negligible amounts appear in the urine. However, when carbohydrates are unavailable or unable to be used as an energy source, fat becomes the predominant body fuel instead of carbohydrates and excessive amounts of ketones are formed as a metabolic byproduct. Higher levels of ketones in the urine indicate that the body is using fat as the major source of energy. Ketone bodies that commonly appear in the urine when fats are burned for energy are acetoacetate and betahydroxybutyric acid. Acetone is also produced and is expired by the lungs. [1] Normally, the urine should not contain a noticeable concentration of ketones to give a positive reading. As with tests for glucose, acetone can be tested by a dipstick or by a lab. The results are reported as small, moderate, or large amounts of acetone. A small amount of acetone is a value under 20 mg/dl; a moderate amount is a value of 3040 mg/dl, and a finding of 80 mg/dl or greater is reported as a large amount.

is a softening of bones in children due to deficiency or impaired metabolism of vitamin D, magnesium,[1] phosphorus or calcium,[2] potentially leading to fractures and deformity. Rickets is

Rickets

among the most frequent childhood diseases in many developing countries. The predominant cause is a vitamin D deficiency, but lack of adequate calcium in the diet may also lead to rickets (cases of severe diarrhea and vomiting may be the cause of the deficiency). Although it can occur in adults, the majority of cases occur in children suffering from severe malnutrition, usually resulting from famine or starvation during the early stages of childhood. Osteomalacia is the term used to describe a similar condition occurring in adults, generally due to a deficiency of vitamin D.[3] The origin of the word "rickets" is probably from the Old English dialect word 'wrickken', to twist. The Greek derived word "rachitis" (, meaning "inflammation of the spine") was later adopted as the scientific term for rickets, due chiefly to the words' similarity in sound.

Signs and symptoms

Signs and symptoms of rickets include:
Bone pain or tenderness dental problems

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muscle weakness (rickety myopathy or "floppy baby syndrome" or "slinky baby" (such that the baby is floppy or slinky-like) increased tendency for fractures (easily broken bones), especially greenstick fractures Skeletal deformity o Toddlers: Bowed legs (genu varum) o Older children: Knock-knees (genu valgum) or "windswept knees" o Cranial, pelvic, and spinal deformities (such as lumbar lordosis) Growth disturbance Chest X ray showing changes consistent with rickets, this changed is usually referred to as Rosary beads of rickets

Hypocalcemia (low level of calcium in the blood) Tetany (uncontrolled muscle spasms all over the body) Craniotabes (soft skull) Costochondral swelling (aka "rickety rosary" or "rachitic rosary") Harrison's groove Double malleoli sign due to metaphyseal hyperplasia Widening of wrist raises early suspicion, it is due to metaphysial cartilage hyperplasia.

An X-ray or radiograph of an advanced sufferer from rickets tends to present in a classic way: bow legs (outward curve of long bone of the legs) and a deformed chest. Changes in the skull also occur causing a distinctive "square headed" appearance. These deformities persist into adult life if not treated. Long-term consequences include permanent bends or disfiguration of the long bones, and a curved back.

Types

Nutritional Rickets Vitamin D Resistant Rickets Vitamin D Dependent Rickets o Type I o Type II Congenital Rickets

Cause
The primary cause of rickets is a vitamin D deficiency.[4] Vitamin D is required for proper calcium absorption from the gut. Sunlight, especially ultraviolet light, lets human skin cells convert Vitamin D from an inactive to active state. In the absence of vitamin D, dietary calcium is not properly absorbed, resulting in hypocalcaemia, leading to skeletal and dental deformities and neuromuscular symptoms, e.g. hyperexcitability. Foods that contain vitamin D include butter, eggs, fish liver oils, margarine, fortified milk and juice, and oily fishes such as tuna, herring, and salmon. A rare X-linked dominant form exists called Vitamin D resistant rickets. Cases have been reported in Britain in recent years[5] of rickets in children of many social backgrounds caused by inability to make vitamin D because the sun's ultraviolet light was not reaching the skin because of persistent use of strong sunblock, or too much "covering up" in sunlight, or spending too much time indoors. Other cases have been reported among the children of some ethnic groups in which mothers avoid exposure to the sun for religious or cultural reasons, leading to a maternal shortage of vitamin D. [6][7] The British Medical Journal reported in 2010 that doctors in Newcastle on Tyne saw 20 cases of rickets per year.

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Diagnosis
Rickets may be diagnosed with the help of:
Blood tests: o Serum calcium may show low levels of calcium, serum phosphorus may be low, and serum alkaline phosphatase may be high. Arterial blood gases may reveal metabolic acidosis X-rays of affected bones may show loss of calcium from bones or changes in the shape or structure of the bones. Bone biopsy is rarely performed but will confirm rickets

5 Osteomalacia
Osteomalacia is the softening of the bones caused by defective bone mineralization secondary to inadequate amounts of available phosphorus and calcium, or because of overactive resorption of calcium from the bone as a result of hyperparathyroidism (which causes hypercalcemia, in contrast to other etiologies). [1] Osteomalacia in children is known as rickets, and because of this, use of the term osteomalacia is often restricted to the milder, adult form of the disease. It may show signs as diffuse body pains, muscle weakness, and fragility of the bones. The most common cause of the disease is a deficiency in vitamin D, which is normally obtained from the diet and/or from sunlight exposure. [2]

General characteristics
Osteomalacia is a generalized bone condition in which there is inadequate mineralization of the bone. Many of the effects of the disease overlap with the more common osteoporosis, but the two diseases are significantly different. There are two main causes of osteomalacia: (1) insufficient calcium absorption from the intestine because of lack of dietary calcium or a deficiency of or resistance to the action of vitamin D; and (2) Phosphate deficiency caused by increased renal losses. Osteomalacia is derived from Greek: osteo- which means "bone", and malacia which means "softness". In the past tense of Brazilian narratives, the disease was also known as malacosteon and its Latin-derived equivalent, mollities ossium.

Causes
The causes of adult osteomalacia are varied, but ultimately result in a vitamin D deficiency:
Insufficient nutritional quantities or faulty metabolism of vitamin D or phosphorus Renal tubular acidosis Malnutrition during pregnancy Malabsorption syndrome [3] Hypophosphatemia Chronic renal failure Tumor-induced osteomalacia [4] Long-term anticonvulsant therapy

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Coeliac disease
[5]

Signs and Symptoms

Weak bones Bone pain Spinal bone pain Pelvic bone pain Leg bone pain Muscle weakness Hypocalcemia Compressed vertebrae Pelvic flattening Fractures Easy fracturing Bone softening Bending of bones Bone fractures

Clinical features
Osteomalacia in adults starts insidiously as aches and pains in the lumbar (lower back) region and thighs, spreading later to the arms and ribs. The pain is symmetrical, non-radiating and is accompanied by sensitivity in the involved bones. Proximal muscles are weak, and there is difficulty in climbing up stairs and getting up from a squatting position. Due to demineralization bones become less rigid. Physical signs include deformities like triradiate pelvis [6] and lordosis. The patient has a typical "waddling" gait. However, those physical signs may derive from a previous osteomalacial state, since bones do not regain their original shape after they become deformed. Pathologic fractures due to weight bearing may develop. Most of the time, the only alleged symptom is chronic fatigue, while bone aches are not spontaneous but only revealed by pressure or shocks. It differs from renal osteodystrophy, where the latter shows hyperphosphatemia

Biochemical findings
Biochemical features are similar to those of rickets. The major factor is an abnormally low vitamin D concentration in blood serum. Major typical biochemical findings are:
The serum calcium is low Urinary calcium is low Serum phosphate is low except in cases of renal osteodystrophy Serum alkaline phosphatase is high

Furthermore, a technetium bone scan will show increased activity.

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Comparison of bone pathology Parathyroid hormone

Calcium Condition Osteoporosis

Phosphate

Alkaline phosphatase

Comments

unaffected unaffected

variable

unaffected

decreased bone mass thick dense bones also known as marble bone

Osteopetrosis

Unaffected unaffected

elevated

unaffected

Osteomalacia and rickets Osteitis fibrosa cystica Paget's disease of bone

decreased decreased

variable

elevated

soft bones

elevated

decreased

elevated

elevated

brown tumors

unaffected unaffected

variable (depending on stage unaffected of disease)

abnormal bone architecture

6 Myxedema
(British English: myxoedema) describes a specific form of cutaneous and dermal edema secondary to increased deposition of connective tissue components (like glycosaminoglycans, hyaluronic acid, and other mucopolysaccharides) in subcutaneous tissue as seen in various forms of hypothyroidism and Graves' disease.[1]:535 It is more common in women than in men. [2]

Terminology
The word originates from , taken from ancient Greek to convey 'mucus' or 'slimy substance' and for swelling.
Hyperthyroid: Myxedema typically presents in specific areas (pretibial myxedema and exophthalmos) and is related to high levels of TSH receptor stimulation and/or inflammation mounted against the TSH receptor itself. Myxedema of the lower legs (called pretibial myxedema), can occur in one to four percent of patients with Graves' [3] disease -- a condition that causes hyperthyroidism. Hypothyroid: Myxedema is also used to describe the clinical syndrome secondary to hypothyroidism. Symptoms can include depression, mental slowness, weakness, bradycardia, fatigue, hypothermia, alopecia, and many others (see symptoms of severe hypothyroidism). Used in this way, myxedema can be considered the adult counterpart of [4] cretinism.

Myxedema coma is rare and establishing the diagnosis requires a high index of suspicion. Myxedema coma represents the severest form of hypothyroidism and has an associated mortality rate of 30 percent to 40 percent. It can occur due to long-standing, untreated hypothyroidism, but is often linked to a precipitant, such as acute infection, myocardial infarction, congestive heart failure, cerebral vascular accident, trauma, or drug toxicity. Several medications can cause hypothyroidism, and patients taking them must be carefully monitored. These medications include amiodarone, lithium, and sedatives. No consensus exists on specific

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thyroid hormone replacement regimens for myxedema coma. Most experts agree that a large intravenous bolus of levothyroxine should be administered (200 to 400 mcg), followed by daily doses of 50 to 100 mcg, based on the patient's weight and comorbidities. Other experts advocate the use of triiodothyronine (T3) or a combination of both T3 and T4. In addition to thyroid replacement therapy, it is important to detect coexisting adrenal insufficiency and treat patients with stress-dose steroids to avoid precipitating adrenal crisis.[5]

Cause
The increased deposition of glycosaminoglycan is not fully understood, however two mechanisms predominate.
Exophthalmos in particular results from TSH receptor stimulation on fibroblasts behind the eyes which leads to increased glycosaminoglycan deposition. It is thought that many cells responsible for forming connective tissue react to increases in TSH levels. Secondarily, in autoimmune thyroid diseases lymphocytes react to the TSH receptor. Thus, in addition to the inflammation within the thyroid, any cell that expresses the TSH receptor will likely experience lymphocytic infiltrates as well. The inflammation can cause tissue damage and scar tissue formation, explaining the deposition of glycosaminoglycans.

The increased deposition of glycosaminoglycans causes an osmotic edema and fluid collection. Hashimoto's thyroiditis is the most common cause of myxedema in the United States. [6]

7 Hirsutism
on women[3] in those parts of the body where terminal hair does not normally occur or is minimal - for example, a beard or chest hair. It refers to a male pattern of body hair (androgenic hair) and it is therefore primarily of cosmetic and psychological concern. Hirsutism is a symptom rather than a disease and may be a sign of a more serious medical condition, especially if it develops well after puberty. The amount and location of the hair is measured by a Ferriman-Gallwey score.
Hirsutism is the excessive hairiness
[2]

Hirsutism affects women and sometimes men, since the rising of androgens causes a male pattern of body hair, sometimes excessive, particularly in locations where women normally do not develop terminal hair during puberty (chest, abdomen, back and face). The medical term for excessive hair growth that affect both men and women is hypertrichosis.

Causes
Hirsutism can be caused by either an increased level of androgens, the male hormones, or an oversensitivity of hair follicles to androgens. Male hormones such as testosterone stimulate hair growth, increase size and intensify the growth and pigmentation of hair. Other symptoms associated with a high level of male hormones include acne and deepening of the voice and increased muscle mass. Growing evidence implicates high circulating levels of insulin in women for the development of hirsutism. This theory is speculated to be consistent with the observation that obese (and thus presumably insulin resistant hyperinsulinemic) women are at high risk of becoming hirsute. Further, treatments that lower insulin levels will lead to a reduction in hirsutism. It is speculated that insulin, at high enough concentration, stimulates the ovarian theca cells to produce androgens. There may also be an effect of high levels of insulin to activate the insulin-like growth factor-I (IGF-1) receptor in those same cells. Again, the result is increased androgen production.

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Signs that are suggestive of an androgen-secreting tumor in a patient with hirsutism is rapid onset, virilization and palpable abdominal mass. The following may be some of the conditions that may increase a woman's normally low level of male hormones:
Polycystic ovary syndrome, abbreviated PCOS, (the most common) Congenital adrenal hyperplasia, in turn mostly caused by 21- hydroxylase deficiency Cushing's disease Tumors in the ovaries or adrenal gland (cancer) Certain medications Insulin resistance Stromal Hyperthecosis - in postmenopausal women Obesity: As there is peripheral conversion of androgens to estrogen in these patients, this is the same mechanism as polycystic ovary syndrome, PCOS. Use of drugs like Tetrahydrogestrinone Adverse effect of Phenytoin
[4]

Diagnosis
One method of evaluating hirsutism is the Ferriman-Gallwey score which gives a score based on the amount and location of hair growth on a woman.[5] Diagnosis of patients with even mild hirsutism should include assessment of ovulation and ovarian ultrasound (because of the high prevalence of polycystic ovary syndrome, as well as 17-hydroxyprogesterone (because of the possibility of finding nonclassic 21-hydroxylase deficiency.[6] Other blood value that may be evaluated in the workup of hirsutism include:
the androgens testosterone and dehydroepiandrosterone sulfate thyroid-stimulating hormone prolactin

If no underlying cause can be identified, the condition is considered idiopathic.

8 Chronic kidney disease

Kidney failure - chronic; Renal failure - chronic; Chronic renal insufficiency; Chronic kidney failure; Chronic renal failure

Chronic kidney disease is the slow loss of kidney function over time. The main function of the kidneys is to remove wastes and excess water from the body.

Causes, incidence, and risk factors

Chronic kidney disease (CKD) slowly gets worse over time. In the early stages, there may be no symptoms. The loss of function usually takes months or years to occur. It may be so slow that symptoms do not appear until kidney function is less than one-tenth of normal. The final stage of chronic kidney disease is called end-stage renal disease (ESRD). At this stage, the kidneys are no longer able to remove enough wastes and excess fluids from the body. The patient needs dialysis or a kidney transplant.

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Chronic kidney disease and ESRD affect more than 2 out of every 1,000 people in the United States. Diabetes and high blood pressure are the two most common causes and account for most cases. Many other diseases and conditions can damage the kidneys, including: Autoimmune disorders (such as systemic lupus erythematosus and scleroderma) Birth defects of the kidneys (such as polycystic kidney disease) Certain toxic chemicals Glomerulonephritis Injury or trauma Kidney stones and infection Problems with the arteries leading to or inside the kidneys Some pain medications and other drugs (such as cancer drugs) Reflux nephropathy (in which the kidneys are damaged by the backward flow of urine into the kidneys) Other kidney diseases

Chronic kidney disease leads to a buildup of fluid and waste products in the body. This condition affects most body systems and functions, including: Blood pressure control Red blood cell production Vitamin D and bone health

Symptoms
The early symptoms of chronic kidney disease are also symptoms of other illnesses. These symptoms may be the only signs of kidney disease until the condition is more advanced. Symptoms may include: Appetite loss General ill feeling and fatigue Headaches Itching (pruritus) and dry skin Nausea Weight loss without trying to lose weight

Other symptoms that may develop, especially when kidney function has gotten worse, include: Abnormally dark or light skin Bone pain Brain and nervous system symptoms: o Drowsiness and confusion o Problems concentrating or thinking o Numbness in the hands, feet, or other areas o Muscle twitching or cramps Breath odor Easy bruising, bleeding, or blood in the stool Excessive thirst

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Frequent hiccups Low level of sexual interest and impotence Menstrual periods stop (amenorrhea) Shortness of breath Sleep problems, such as insomnia, restless leg syndrome, and obstructive sleep apnea Swelling of the feet and hands (edema) Vomiting, typically in the morning

Signs and tests

High blood pressure is almost always present during all stages of chronic kidney disease. A nervous system exam may show signs of nerve damage. The health care provider may hear abnormal heart or lung sounds when listening with a stethoscope. A urinalysis may show protein or other changes. These changes may appear 6 months to 10 or more years before symptoms appear. Tests that check how well the kidneys are working include: Creatinine clearance Creatinine levels BUN

Chronic kidney disease changes the results of several other tests. Every patient needs to have the following checked regularly, as often as every 2 - 3 months when kidney disease gets worse: Albumin Calcium Cholesterol Complete blood count (CBC) Electrolytes Magnesium Phosphorous Potassium Sodium

Causes of chronic kidney disease may be seen on: Abdominal CT scan Abdominal MRI Abdominal ultrasound Kidney biopsy Kidney scan Kidney ultrasound

This disease may also change the results of the following tests:

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Erythropoietin PTH Bone density test Vitamin D

Diabetes Insipidus,

Diabetes insipidus (DI) causes frequent urination. The large volume of urine is diluted, mostly water. To make up for lost water, you may feel the need to drink large amounts. You are likely to urinate frequently, even at night, which can disrupt sleep or, on occasion, cause bedwetting. Because of the excretion of abnormally large volumes of dilute urine, you may quickly become dehydrated if you do not drink enough water. Children with diabetes insipidus may be irritable or listless and may have fever, vomiting , or diarrhea. In its clinically significant forms, diabetes insipidus is a rare disease.

Diabetes Insipidus versus Diabetes Mellitus

Diabetes insipidus should not be confused with diabetes mellitus, which results from insulin deficiency or resistance leading to high blood glucose. Diabetes insipidus and diabetes mellitus are unrelated, although they can have similar signs and symptoms, like excessive thirst and excessive urination. Diabetes mellitus (DM) is far more common than diabetes insipidus and receives more news coverage. DM has two forms, referred to as type 1 diabetes (formerly called juvenile diabetes, or insulin-dependent diabetes mellitus, or IDDM) and type 2 diabetes (formerly called adult-onset diabetes, or noninsulin-dependent diabetes mellitus, or NIDDM). Diabetes insipidus is a different form of illness altogether.

Diagnosis of Diabetes Insipidus

Because diabetes mellitus is more common and because diabetes mellitus and diabetes insipidus have similar symptoms, a health care provider may suspect that a patient with diabetes insipidus has DM. But testing should make the diagnosis clear. Your physician must determine which type of diabetes insipidus is involved before proper treatment can begin. Diagnosis is based on a series of tests, including urinalysis and a fluid deprivation test. Urinalysis is the physical and chemical examination of urine. The urine of a person with diabetes insipidus will be less concentrated. Therefore, the salt and waste concentrations are low, and the amount of water excreted is high. A physician evaluates the concentration of urine by measuring how many particles are in a kilogram of water (osmolality) or by comparing the weight of the urine to an equal volume of distilled water (specific gravity). A fluid deprivation test helps determine whether diabetes insipidus is caused by (1) excessive intake of fluid, (2) a defect in ADH production, or (3) a defect in the kidneys' response to ADH. This test measures changes in body weight, urine output, and urine composition when fluids are withheld. Sometimes measuring blood levels of ADH during this test is also necessary. In some patients, an MRI (magnetic resonance imaging) of the brain may be necessary as well.

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10 Obesity
Obesity means having too much body fat. It is not the same as being overweight, which means weighing too much. A person may be overweight from extra muscle, bone, or water, as well as from having too much fat. Both terms mean that a person's weight is higher than what is thought to be healthy for his or her height.

Causes, incidence, and risk factors

Taking in more calories than you burn can lead to obesity because the body stores unused calories as fat. Obesity can be caused by: Eating more food than your body can use Drinking too much alcohol Not getting enough exercise

Many obese people who lose large amounts of weight and gain it back think it is their fault. They blame themselves for not having the willpower to keep the weight off. Many people regain more weight than they lost. Today, we know that biology is a big reason why some people cannot keep the weight off. Some people who live in the same place and eat the same foods become obese, while others do not. Our bodies have a complex system to help keep our weight at a healthy level. In some people, this system does not work normally. Other factors that affect weight include: The way we eat when we are children can affect the way we eat as adults. The way we eat over many years becomes a habit. It affects what we eat, when we eat, and how much we eat. We are surrounded by things that make it easy to overeat and hard to stay active: o Many people do not have time to plan and make healthy meals. o More people today work desk jobs compared to more active jobs in the past. o People with less free time have less time to exercise.

The term "eating disorder" means a group of medical conditions that have an unhealthy focus on eating, dieting, losing or gaining weight, and body image. A person may be obese, follow an unhealthy diet, and have an eating disorder all at the same time. Sometimes, medical problems or treatments cause weight gain, including: Underactive thyroid gland (hypothyroidism) Medicines such as birth control pills, antidepressants, and antipsychotics

Other things that can cause weight gain are: Quitting smoking. Most people who quit smoking gain 4 - 10 pounds in the first 6 months after quitting. Some people gain as much as 25 - 30 pounds. Stress, anxiety, feeling sad, or not sleeping well

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For women: o Menopause -- women may gain 12-15 pounds during menopause o Not losing the weight they gained during pregnancy

Signs and tests

The health care provider will perform a physical exam and ask questions about your medical history, eating habits, and exercise routine. The two most common ways to measure health risks from your weight are: Body mass index (BMI) Waist circumference (your waist measurement in inches)

BMI is measured using height and weight. You and your health care provider can use your BMI to estimate how much body fat you have. Your waist measurement is another way to estimate how much body fat you have. Extra weight around your middle or stomach area increases your risk for type 2 diabetes, heart disease, and stroke. People with "appleshaped" bodies (meaning their waist is bigger than their hips) also have an increased risk for these diseases. Skin fold measurements may be taken to check your body fat percentage. Blood tests may be done to look for thyroid or hormone problems that could lead to weight gain.

11 Kidney stones
A kidney stone is a solid mass made up of tiny crystals. One or more stones can be in the kidney or ureter at the same time.

Causes, incidence, and risk factors

Kidney stones are common. Some types run in families. They often occur in premature infants. There are different types of kidney stones. The exact cause depends on the type of stone. Stones can form when urine contains too much of certain substances. These substances can create small crystals that become stones. The stones take weeks or months to form. Calcium stones are most common. They are more common in men between age 20-30. Calcium can combine with other substances, such as oxalate (the most common substance), phosphate, or carbonate to form the stone. Oxalate is present in certain foods such as spinach. It's also found in vitamin C supplements. Diseases of the small intestine increase your risk of these stones. Cystine stones can form in people who have cystinuria. This disorder runs in families and affects both men and women. Struvite stones are mostly found in women who have a urinary tract infection. These stones can grow very large and can block the kidney, ureter, or bladder. Uric acid stones are more common in men than in women. They can occur with gout or chemotherapy.

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Other substances also can form stones including the medications acyclovir, indinavir, and triamterene.

The biggest risk factor for kidney stones is not drinking enough fluids. Kidney stones are more likely to occur if you make less than 1 liter of urine a day. That's slightly more than a quart. .

Symptoms
You may not have symptoms until the stones move down the tubes (ureters) through which urine empties into your bladder. When this happens, the stones can block the flow of urine out of the kidneys. The main symptom is severe pain that starts suddenly and may go away suddenly: Pain may be felt in the belly area or side of the back Pain may move to groin area (groin pain) or testicles (testicle pain)

Other symptoms can include: Abnormal urine color Blood in the urine Chills Fever Nausea Vomiting

Signs and tests

The health care provider will perform a physical exam. The belly area (abdomen) or back might feel sore. Tests that may be done include: Blood tests to check calcium, phosphorus, uric acid, and electrolyte levels Kidney function tests Urinalysis to see crystals and look for red blood cells in urine Examination of the stone to determine the type

Stones or a blockage can be seen on: Abdominal CT scan Abdominal/kidney MRI Abdominal x-rays Intravenous pyelogram (IVP) Kidney ultrasound Retrograde pyelogram

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12 Tumor Markers; AFP, HCG, CA-125
Tumor markers are molecules occurring in blood or tissue that are associated with cancer and whose measurement or identification is useful in patient diagnosis or clinical management. The ideal marker would be a "blood test" for cancer in wich a positive result would occur only in patients with malignancy, one that would correlate with stage and response to treatment and that was easily and reproducibly measured. No tumor marker now available has met this ideal. Tumor markers can be used for one of four purposes: (1) screening a healthy population or a high risk population for the presence of cancer; (2) making a diagnosis of cancer or of a specific type of cancer; (3) determining the prognosis in a patient; (4) monitoring the course in a patient in remission or while receiving surgery, radiation, or chemotherapy. No test meets all of those requirements. Specifically, no marker has been established as a pratical cancer screening tool either in a general healthy population or in most high risk poulations. The reason for this is the relative lack of sensitivity and specificity of the available tests, given the low prevalence of cancers in most population groups. Given the low prevalence of cancer in general, even tests that are highly sensitive and specific may have low predictive values. Tumor markers include many substances that are not readily systematically organized.Those discussed here are generally products or the cancer cell, although none is unique to cancer cells; they represent aberrant tumor production of a normal element. Some markers are produced by the organism in response to the cancer's presence.

Tumor Antigens
Include markers defined by both monoclonal antibodies and polyclonal antisera, often the so called oncofetal antigens. The oncofetal substances, present in embryo or fetus, diminish to low levels in the adult but reappear in the tumor.

Carcinoembryonic Antigen
Tumor marker, CEA: Carcinoembryonic antigen (CEA) is a protein found in many types of cells but associated with tumors and the developing fetus. CEA is tested in blood. The normal range is <2.5 ng/ml in an adult non-smoker and <5.0 ng/ml in a smoker. The CEA was one of the first oncofetal antigens to be described and exploited clinically. It is a complex glycoprotein of molecular weight 20,000, that is associated with the plasma membrane of tumor cells, from wich it may be released into the blood. Although CEA was first indentified in colon cancer, an abnormal CEA blood level is specific neither for colon cancer nor for malignancy in general. Elevated CEA levels are found in a variety of cancers other than colonic, including pancreatic, gastric, lung, and breast. It is also detected in benign conditions including cirrhosis, inflamatory bowel disease, chronic lung disease, and pancreatitis. The CEA was found to be elevated in up to 19 percent of smokers and in 3 percent of a healthy control population. Thus, the test for CEA cannot substitute for a pathological diagnosis. As a screening test, the CEA is also inadequate. Since cancer prevalence in a healthy population is low, an elevated CEA has an unacceptably low positive predictive value, with excess false positives. Also, since elevated CEA occurs in the advanced stage of incurable cancer but is low in the early, curable disease, the likelihood of a positive result affecting a patient's survival is diminished. The CEA has been sugested as having prognostic value for patients with colon cancer. Preoperative CEA values have been positively correlated with stage and negatively correlated with disease free survival. Although not satisfactory for screening a healthy population, CEA has been used to monitor recurrence. Early data suggested that CEA prededed clinical relapse by several months. Subsequently, several investigators have examined intensive, serial CEA monitoring as an indicator for second look surgery in the hope that relapse could be detected at a time when surgical ressection for cure was still possible. Criteria for reoperation included a significant rise of CEA above a base line level on serial determinations and absence of obvious unresectable disease on staging workup. Determinations of CEA should be done frequently: at a minimum of every 3 months and if possible every 1 month to 2 months. Elevations above baseline should be verified rapidly to exclude laboratory error.

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The CEA is of some use as a monitor in treatment. Usually the CEA returns to normal within 1 to 2 months of surgery, but if it returns elevated persistent disease may be indicated. The test is not infallible in patients treated with radiotherapy and chemotherapy but can be useful in those whose tumor is not measurable. The CEA is often positive in malignancies other than colonic. In cancer of the breast, lung, pancreas, stomach, and ovary the CEA may be elevated and can be used to monitor the progress of disease or response to treatement.

Alpha-Fetoprotein
Alpha-Fetoprotein is a normal fetal serum protein synthesized by the liver, yolk sac, and gastrointestinal tract that shares sequence homology with albumin. It is a major component of fetal plasma, reaching a peak concentration of 3 mg/ml at 12 weeks of gestation. Following birth, it clears rapidily from the circulation, having a half life of 3.5 days, and its concentration in adult serum is less than 20 ng/ml. AFP is of importance in diagnosing hepatocellular carcinoma and may be useful in screening procedures. AFP elevation is more common in areas where hepatocellular carcinoma is endemic, such as Africa and in patients who are HBsAg positive. AFP is a marker for hepatocellular and germ cell (nonseminoma) carcinoma.1 It is a glycoprotein produced in large amounts during fetal life and is homologous to albumin. In healthy adults, less than 10 g/L of AFP is found in the circulation. AFP is elevated in normal pregnancy, benign liver disease (hepatitis, cirrhosis), as well as in cancer. An elevated AFP has been termed by Sell "the single most discriminating laboratory test indicative of malignant disease now available." As such, it could be valuable in screening for hepatocellular carcinoma in high risk populations. AFP is elevated in testicular germ cell tumors containing embryonal or endodermal sinus elements. A defenitive positive marker value is highly sensitive in indicating relapse or response to treatment. The AFP is less frequently elevated in other malignancies such as pancreatic cancers, gastric cancers, colonic cancers, and bronchogenic cancers. This elevation was not necessarily associated with liver metastases. The AFP is rarely elevated in healthy persons, and a rise is seen in only a few disease states. Elevation occurs in certain liver diseases, especially acute viral or drug induced hepatitis and conditions associated with hepatic regeneration. In general, the elevations are under 500 ng/ml and do not denote hepatocellular carcinoma. Is also elevated in ataxiatelangiectasia and in hereditary tyrosinosis. Thus, AFP is a useful marker in hepatocellular carcinoma and germ cell tumors, the only conditions associated with extreme elevations greater than 500 ng/ml. In both tumors it has value in diagnosis and monitoring of therapy. In the former, wich is one of the most common tumors worldwide, AFP may be of use in screening.

CA 125
CA125 is an antigen present on 80 percent of nonmucinous ovarian carcinomas. It is defined by a monoclonal antibody ( OC125 ) that was generated by immunizing laboratory mice with a cell line established from human ovarian carcinoma. It circulates in the serum of patients with ovarian carcinoma and was therefore investigated for possible use as a marker. CA125 is often elevated in patients with ovarian cancer, its level following the patient's clinical course. With surgical resection or chemotherapy, the level correlates with patient response. Thus, it is superior to other markers such as CEA. The CA125 is elevated in other cancers including endometrial, pancreatic, lung, breast, and colon cancer, and in menstruation, pregnancy, endometriosis, and other gynecologic and non gynecologic conditions. Because of the low prevalence of ovarian cancer, the test is not itself useful in screening.

CA19-9
CA19-9 is a monoclonal antibody generated against a colon carcinoma cell line to detect a monosialoganglioside found in patients with gastrointestinal adenocarcinoma. It is found it to be elevated in 21 to 42 percent of cases of gastric cancer, 20 to 40 percent of colon cancer, and 71 to 93 percent of pancreatic cancer, and has been proposed to differentiate benign from malignant pancreatic disease, but this capability remains to be established.

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Prostate-Specific Antigen
The PSA screening test is a blood test that looks for a specific tumor marker. In general, tumor markers are produced by the tumor itself or by our body in response to the presence of cancer or non-cancerous conditions. If a tumor marker level is higher than normal, the patient is examined more closely to look for cancer or other conditions. The most commonly tested tumor marker for the prostate gland is prostate specific antigen. It is normally present in low levels in the blood of all adult men. The normal range is 0 to 4 ng/ml. PSA is prostate-specific, not cancer-specific. A variety of conditions can raise PSA levels: prostatitis (prostate inflammation), benign prostatic hypertrophy (prostate enlargement), and prostate cancer. PSA levels can also be influenced by a number of other things. Some prostate glands normally produce more PSA than others. PSA levels tend to increase with age. And, PSA levels can vary with race: African Americans often have higher PSA levels; Asian men often have lower PSA levels. PSA seems to have the capability of achieving at least one of the characteristics of an ideal tumor marker- tissue specificity; it is found in normal prostatic epithelium and secretions but not in other tissues. It is a glycoprotein, whose function may be to lyse the seminal clot. PSA is highly sensitive for the pesence of prostatic cancer. The elevation correlated with stage and tumor volume. It is predictive of recurrence and response to treatment. Finally, the antigen has prognostic value in patients with very high values prior to surgery are likely to relapse. Unfortunately, PSA is detectable in normal men and often is elevated in benign prostatic hypertrophy, which may limit its value as a screening tool for prostate cancer. A recent study has shown that PSA combined with rectal exam is a better method of detecting prostate cancer than rectal exam alone. Age-Specific Reference for Serum PSA (Reference Range [ng/ml]) Age Range (Years) Black Caucasians Japanese 40 - 49 0.0 - 2.0 0.0 - 2.5 0.0 - 2.0 50 - 59 0.0 - 4.0 0.0 - 3.5 0.0 - 3.0 60 - 69 0.0 - 4.5 0.0 - 4.5 0.0 - 4.0 70 - 79 0.0 - 5.5 0.0 - 6.5 0.0 - 5.0 Hormones: Hormones are produced by many tumors. The hormone may be a natural product of its associated organ or represent abnormal synthesis reflecting unregulated cancer cell metabolism. Examples include insulin production by islet cell tumor, calcitonin by medullary thyroid carcinoma, and catecholamines by pheochromocytoma. Or it may be that the hormone is not a natural product of its associated organ, in which case is designated "ectopic". Examples include the production of ACTH and ADH by lung cancers. In this section, discussion is limited to human chorionic gonadotropin. Other hormones will be discussed in another review.

Human Chorionic Gonadotropin

HCG is a glycoprotein consisting of subunits a e b, which are nonconvalently linked. The hormone is normally produced by the syncytiotrophoblastic cells of the placenta and is elevated in pregnancy. Its most important uses as a tumor marker are in gestational trophoblastic disease and germ cell tumors. All gestational trophoblastic tumors produce HCG, and it is a valuable marker in these tumors, screening reliably in all cases and indicating poor responses to treatment. The level correlates with tumor mass and thus has prognostic value. HCG is extremely sensitive, being elevated in women with minute amounts of tumor. The patient is followed weekly during treatment, and at the completion of treatment indefinite follow up is advised to detect recurrence. HCG is essential in managing trophoblastic neoplasms. The level of HCG is occasionally elevated in other cancers including those of breast, lung, and gastrointestinal tract, but in these diseases it has found little clinical application.