Endocrinology Questions

x
Anatomy Physiolo...
E
children, AGS often causes enlargement of the penis or clitoris
and the premature onset of puberty (fig. 17.28). Prenatal AGS can
result in newborn girls exhibiting masculinized genitalia and being
misidentified as boys. In women, A

Anatomy and Physiology

Endocrinology Solutions

x Anatomy Physiolo... E children, AGS often causes enlargement of the penis or clitoris and the premature onset of puberty (fig. 17.28). Prenatal AGS can result in newborn girls exhibiting masculinized genitalia and being misidentified as boys. In women, AGS produces such masculin- izing effects as increased body hair, deepening of the voice, and beard growth 17.7e Diabetes Mellitus The world's most prevalent metabolic disease is diabetes mellitus, affecting about 7% of the U.S. population and even more in areas such as Scandinavia and the Pacific Islands. It is the leading cause of adult blindness, renal failure. gangrene, and the necessity for limb amputations, and warrants a more extended discussion than the less common endocrine diseases. The pathology of DM is de scribed here, and the chapter ends with an essay on the history of insulin (see Deeper Insight 17.4). Diabetes mellitus (DM) can be defined as a disruption of carbohydrate, fat, and protein metabolism resulting from the hyposecretion or inaction of insulin. The classic signs and FIGURE 17.28 Adrenogenital Syndrome (AGS). These are the genitals of a female with AGS, masculinized by prenatal hypersecretion of adrenal androgens. Note the resemblance of the labia majora to a scrotum and enlargement of the clitoris to resemble a penis. Infants with AGS are easily mistaken for boys and raised as such. Medicimage RM Medical Images Harvey Cushing (1869-1939). American physician diabetolow through mells honey CHAPTER 17 The Endocrine System 647 symptoms with which patients often first present to a physi- cian are the three polys”: polyuria" (excessive urine output). polydipsia(intense thirst), and polyphagia (ravenous hun- ger). Blood and urine tests can confirm a diagnosis of DM by revealing three further signs: hyperglycemia (elevated blood glucose), glycosuria glucose in the urine), and ketonuria (ketones in the urine). DM was originally named for the sweet- ness of the urine stemming from glycosuria. Before the advent of chemical tests for glucose, physicians tasted their patients' urine as part of their diagnostic process. A little knowledge of kidney physiology is necessary to under- stand why glycosuria and polyuria occur. The kidneys filter blood plasma and convert the filtrate to urine. In a healthy person, the kidney tubules remove all glucose from the filtrate and return it to the blood, so there is little or no glucose in the urine. Water fol- lows the glucose and other solutes by osmosis, so the tubules also reclaim most of the water in the filtrate. But like any other carrier-mediated transport system, there is a limit to how fast the glucose transporters of the kidney can work. The maximum rate of reabsorption is called the transport maxi- mum, T. (see fig. 3.16). Because of the high blood glucose level in diabetes mellitus, glucose enters the kidney tubules so rapidly that it exceeds the T. and the tubules can't reabsorb it fast enough. The excess passes through into the urine. Glucose and ketones in the tubules also raise the osmolarity of the tubular fluid and cause osmotic diuresis-water remains in the tubules with these solutes. so large amounts of water are passed in the urine. This accounts for the polyuria, dehydration, and thirst of diabetes. A person with untreated DM may pass 10 to 15 L of urine per day, compared with 1 or 2 L in a healthy person. Types and Treatment There are two forms of diabetes mellitus: type 1 and type 2. These were formerly called juvenile-onset or insulin-dependent DM, and adult-onset or non-insulin-dependent DM, respectively. These terms have lately been abandoned because they are too mislead ing. Although insulin is always used to treat type 1, it is frequently used for type 2 diabetes as well, and either type can occur at any age. Indeed, with the burgeoning problem of childhood obesity. nearly half of all new cases of childhood diabetes are now type 2. Type 1 diabetes mellitus accounts for 5% to 10% of cases in the United States. What causes it? It begins with heredity. Several genes have been identified that predispose a person to type 1 DM. Then, when a genetically susceptible individual is infected by cer- tain viruses (rubella, cytomegalovirus, or a few others), certain immune cells (CD4 and CD8 T cells discussed in section 21.4) attack and destroy pancreatic beta cells. To a great extent, this destruction is tolerated and produces no disease, but when 80% to 90% of the beta cells are gone, insulin falls to such a critically low level that it can no longer regulate glycemia, the blood glucose level. Now comes the problematic hyperglycemia and all of its insidious complications. Type 1 diabetes is usually diagnosed be- fore the age of 30, but may occur later. Its victims require insulin to survive usually periodic injections or continual subcutaneous delivery by a small insulin pump worn on the body. A dry insulin inhaler is now available, but is not suitable for all patients. Meal planning, exercise, and self-monitoring of blood glucose levels are also important aspects of the treatment regimen. Some 90% to 95% of diabetics, however, have type 2 DM, and a great many more are prediabetic. Here, the chief problem is not lack of insulin, but insulin resistance-unresponsiveness of the tar get cells to the hormone. The level of insulin may actually be very high in the early stage of the disease, although it later tends to fall to normal or subnormal levels. Again, heredity is one of the causes, al- though no one gene, or even a mere few.can be blamed for the dis- ease; nearly 100 genes are known, so far, to elevate the risk of type 2 DM. There are great differences in prevalence from one ethnic group to another, it is relatively high, for example, among people of Native American, Hispanic, and Asian descent. It also has a ten- dency to run in families, and shows high concordance between ge- netically identical twins--if one twin develops type 2 DM, there is more than a 90% probability that the other will too. Other important risk factors are age, obesity, and a sedentary lifestyle. All of these are accompanied by the progressive replacement of muscular tissue with fat. Muscle plays a highly important role in absorbing blood glucose and buffering glycemia, so as muscle mass diminishes, a person becomes less and less able to regulate glycemia. Type 2 DM develops slowly and is usually diagnosed after age 40, but it is becoming increasingly prevalent in young people be- cause of early obesity. Aside from the loss of the glucose-buffering role of muscle, another apparent factor in type 2 DM is that adi- pose tissue secretes chemical signals that indirectly interfere with glucose transport into most cells—so the more body fat, the less efficient is glucose uptake. It is no surprise, then, that type 2 DM can often be successfully managed through a weight-loss program of diet and exercise, often supplemented with glycemia-lowering oral medications such as metformin and drugs to lower blood pres- sure and blood lipids. If these approaches prove inadequate, sup- plemental insulin therapy is also employed. About 12% of patients with type 2 DM are treated with insulin alone and another 14% with insulin combined with oral hypoglycemic agents (OHAS). Pathogenesis When cells cannot absorb glucose, they must get their energy some place else: they metabolize fat and protein. In time, this leads to muscular atrophy, emaciation, and weakness. Before insulin ther- apy was introduced in 1922, the victims of type 1 DM wasted away to an astonishing extent (see Deeper Insight 17.4). Diabetes was described in the first century as "a melting down of the flesh and limbs into urine." Adult patients weighed as little as 27 to 34 kg (60-75 lb) and looked like victims of severe famine. Their breath had a disagreeable sweet ketone smell, like rotten apples. One typi- cal patient was described by medical historian Michael Bliss as "barely able to lift his head from his pillow, crying most of the time from pain, hunger, and despair." In the terminal stage, patients became increasingly drowsy, gasped for air, became comatose, a poly = much, excessive, uri = urine poly = much excessive departe drinking poly = much excessive phagie = cating hyperences, ghe = sugar, glucose, emia = blood condition glyce = glucose, sugar, uria = urine condition

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