Most Forms of Type 1 Diabetes Mellitus Involve an Autoimmune Disorder

Type 1 diabetes is characterized by the inability of beta cells to produce physiologically appropriate amounts of insulin. In some instances, this may result from a mutation in the preproinsulin gene. However, the most common form of type 1 diabetes results from destruction of the pancreatic beta cells by the immune system. The initial pathological event is insulitis, involving a lymphocytic attack on beta cells. Antibodies to beta cell cell-surface antigens have also been found in the...

Insulin Affects the Metabolism of Carbohydrates Lipids and Proteins in Liver Muscle and Adipose Tissues

The primary targets for insulin are liver, skeletal muscle, and adipose tissues. Insulin has multiple individual actions in each of these tissues, the net result of which is fuel storage. Mechanism of Insulin Action. Although insulin was one of the first peptide hormones to be identified, isolated, and characterized, its exact mechanism of action remains elusive. The insulin receptor is a heterotetramer, consisting of a pair of a p subunit complexes held together by disulfide bonds (Fig. 35.3)....

Functional Anatomy Of The Adrenal Gland

The human adrenal glands are paired, pyramid-shaped organs located on the upper poles of each kidney. The adrenal gland is actually a composite of two separate endocrine organs, one inside the other, each secreting separate hormones and each regulated by different mechanisms. The outer portion or cortex of the adrenal gland completely surrounds the inner portion or medulla and makes up most of the gland. During embryonic development, the cortex forms from mesoderm,- the medulla arises from...

The Fetal Endocrine System Gradually Matures

The protective intrauterine environment postpones the initiation of some physiological functions that are essential for life after birth. For example, the fetal lungs and kidneys do not act as organs of gas exchange and excretion because their functions are carried out by the placenta. Constant isothermal surroundings alleviate the need to expend calories to maintain body temperature. The gastrointestinal tract does not carry out digestive activities, and fetal bones and muscles do not support...

Osteoporosis Is a Reduction in Bone Mass

Osteoporosis is a major health problem, particularly because older adults are more prone to this disorder and the average age of the population is increasing see Clinical Fo Effects of 1,2 5-clihyclroxycholecalciferol ttmmU mm i,25- OH 2 D3 on calcium and phosphate metabolism. cus Box 36.1 . Osteoporosis involves a reduction in total bone mass with an equal loss of both bone mineral and organic matrix. Several factors are known to contribute directly to osteoporosis. Long-term dietary calcium...

Increased Blood Glucose Stimulates the Secretion of Insulin

Chemoreceptors That Detect Blood Acidity

A variety of factors, including other pancreatic hormones, are known to influence insulin secretion. The primary physiological regulator of insulin secretion, however, is the blood glucose concentration. Proinsulin Synthesis. The gene for insulin is located on the short arm of chromosome 11 in humans. Like other hormones and secretory proteins, insulin is first synthesized by ribosomes of the rough ER as a larger precursor peptide that is then converted to the mature hormone prior to secretion...

Body Temperatures And Heat Transfer In The Body

Temperature Body Shell

The body is divided into a warm internal core and a cooler outer shell Fig. 29.2 . Because the temperature of the shell is strongly influenced by the environment, its temperature is not regulated within narrow limits as the internal body temperature is, even though thermoregulatory responses strongly affect the temperature of the shell, especially its outermost layer, the skin. The thickness of the shell depends on the environment and the body's need to conserve heat. In a warm environment, the...

Type 2 Diabetes Mellitus Primarily Originates in the Target Tissue

Acute Complications Diabetes Mellitus

Type 2 diabetes mellitus results primarily from impaired ability of target tissues to respond to insulin. There are multiple forms of the disease, each with a different etiology. In some cases, it is a permanent, lifelong disorder,- in others, it results from the secretion of counterregulatory hormones in a normal e.g., pregnant or pathophysiological e.g., Cushing's disease state. Gestational diabetes occurs in 2 to 5 of all pregnancies but usually disappears after delivery. Women who have had...

The Basal Ganglia Are Extensively Interconnected

Input Substantia Nigra Pars Compacta

Although the circuitry of the basal ganglia appears complex at first glance, it can be simplified into input, output, and internal pathways Fig. 5.16 . Input is derived from the cerebral cortex and is directed to the striatum and the sub-thalamic nucleus. The predominant nerve cell type in the striatum is termed the medium spiny neuron, based on its cell body size and dendritic structure. This type of neuron receives input from all of the cerebral cortex except for the primary visual and...

Disorders of Sexual Development Can Manifest Before or After Birth

Gonadal Dysgenesis

Normal sexual development depends on a complex, orderly sequence of events that begins during early fetal life and is completed at puberty. Any deviation can result in infertility, sexual dysfunction, or various degrees of intersexuality or hermaphroditism. A true hermaphrodite possesses both ovarian and testicular tissues, either separate or combined as ovotestes. A pseudohermaphrodite has one type of go-nads but a different degree of sexuality of the opposite sex. Sex is normally assigned...

Tissue Metabolism Influences Blood Flow

Normal Oxygen Flow Rate

In all organs, an increase in metabolic rate is associated with increased blood flow and extraction of oxygen to meet the metabolic needs of the tissues. In addition, a reduction in oxygen within the blood is associated with dilation of the arterioles and increased blood flow, assuming neural reflexes to hypoxia are not activated. The local regulation of the microvasculature in response to the metabolic needs of tissues involves many different types of cellular mechanisms, one of which is...

Acute and Chronic Exercise Increases Insulin Sensitivity Insulin Receptor Density and Glucose Transport into Muscle

Insulin Exercise Response

Though skeletal muscle is omnivorous, its work intensity and duration, training status, inherent metabolic capacities, and substrate availability determine its energy sources. For very short-term exercise, stored phosphagens ATP and creatine phosphate are sufficient for crossbridge interaction between actin and myosin, even maximal efforts lasting 5 to 10 seconds require little or no glycolytic or oxidative energy production. When work to exhaustion is paced to be somewhat longer in duration,...

Hypogonadism Can Result From Defects at Several Levels

Male hypogonadism may result from defects in spermato-genesis, steroidogenesis, or both. It may be a primary defect in the testes or secondary to hypothalamic-pituitary dysfunction, and determining whether the onset of gonadal failure occurred before or after puberty is important in establishing the cause. However, several factors must be considered. First, normal spermatogenesis almost never occurs with defective steroidogenesis, but normal steroidogenesis can be present with defective...

Endothelial Cells Can Release Chemicals That Cause Relaxation or Constriction of Arterioles

An important contributor to local vascular regulation is released by endothelial cells. This substance, endothelium-derived relaxing factor EDRF , is released from all arteries, microvessels, veins, and lymphatic endothelial cells. EDRF is nitric oxide NO , which is formed by the action of nitric oxide synthase on the amino acid arginine. NO causes the relaxation of vascular smooth muscle by inducing an increase in cyclic guanosine monophosphate cGMP . When cGMP is increased, the smooth muscle...

Muscle Cells Obtain ATP From Several Sources

Atp Sourcers Skeletal Muscle

Although ATP is the immediate fuel for the contraction process, its concentration in the muscle cell is never high enough to sustain a long series of contractions. Most of the immediate energy supply is held in an energy pool of the compound creatine phosphate or phosphocreatine PCr , which is in chemical equilibrium with ATP. After a molecule of ATP has been split and yielded its energy, the resulting ADP molecule is readily rephosphorylated to ATP by the high-energy phosphate group from a...

GH Regulates Growth During Childhood and Remains Important Throughout Life

Dehydration Negative Feedback

As its name implies, growth hormone GH promotes the growth of the human body. It does not appear to stimulate fetal growth, nor is it an important growth factor during the first few months after birth. Thereafter, it is essential for the normal rate of body growth during childhood and adolescence. Growth hormone also called somatotropin is secreted by the anterior pituitary throughout life and remains physiologically important even after growth has stopped. In addition to its growth-promoting...

The Kidneys Play a Dominant Role in Regulating Na1 Balance

Ecf Volume And Diarrhea

Figure 24.11 summarizes Na balance throughout the body. Dietary intake of Na varies and, in a typical American diet, amounts to about 100 to 300 mEq day, mostly in the form of NaCl. Ingested Na is mainly absorbed in the small intestine and is added to the ECF, where it is the major determinant of the osmolality and the amount of water in or volume of this fluid compartment. About 50 of the body's Na is in the ECF, about 40 in bone, and about 10 within cells. Losses of Na occur via the skin,...

An Electroencephalogram Records Electrical Activity of the Brains Surface

Abnormal Eeg Waves

The influence of the ascending reticular activating system on the brain's activity can be monitored via electroen-cephalography. The electroencephalograph is a sensitive recording device for picking up the electrical activity of the brain's surface through electrodes placed on designated sites on the scalp. This noninvasive tool measures simultaneously, via multiple leads, the electrical activity of the major areas of the cerebral cortex. It is also the best diagnostic tool available for...

Fluid Movement In Capillaries

Pulmonary Edema Osmotic

Hypoxia-Induced Pulmonary Hypertension Hypoxia has opposite effects on the pulmonary and systemic circulations. Hypoxia relaxes vascular smooth muscle in systemic vessels and elicits vasoconstriction in the pulmonary vasculature. Hypoxic pulmonary vasoconstriction is the major mechanism regulating the matching of regional blood flow to regional ventilation in the lungs. With regional hypoxia, the matching mechanism automatically adjusts regional pulmonary capillary blood flow in response to...

The Liver Is Important in Carbohydrate Metabolism

Carbohydrate Metabolism Liver

The liver is extremely important in maintaining an adequate supply of nutrients for cell metabolism and regulating blood glucose concentration Fig. 28.3 . After the ingestion of a meal, the blood glucose increases to a concentration of 120 to 150 mg dL, usually in 1 to 2 hours. Glucose is taken up by hepatocytes by a facilitated carrier-mediated process and is converted to glucose 6-phosphate and then UDP-glucose. UDP-glucose can be used for glycogen synthesis, or glycogenesis. It is generally...

Hypertension Is a Sustained Elevation in Blood Pressure

Epidemiological data show that chronically elevated blood pressure is associated with excess cardiovascular morbidity and mortality. In adults, hypertension is defined as sustained systolic blood pressure of 140 mm Hg or higher, sustained diastolic blood pressure of 90 mm Hg or higher, or taking antihypertensive medication. Hypertension causes damage to the arterial system, the myocardium, the kidneys, and the nervous system, including the retinas. Medical treatment that lowers blood pressure...

Digestion And Absorption Of Lipids

Docosahexaenoic Acid Molecule

Lipids are a concentrated form of energy. They provide 30 to 40 of the daily caloric intake in the Western diet. Lipids are also essential for normal body functions, as they form part of cellular membranes and are precursors of bile acids, steroid hormones, prostaglandins, and leukotrienes. The human body is capable of synthesizing most of the lipids it requires with the exception of the essential fatty acids linoleic acid C 18 2, an 18-carbon long fatty acid with two double bonds and...

Digestion And Absorption Of Carbohydrates

Structure Glycogen

The digestion and absorption of dietary carbohydrates takes place in the small intestine. These are extremely efficient processes, in that essentially all of the carbohydrates consumed are absorbed. Carbohydrates are an extremely important component of food intake, since they constitute about 45 to 50 of the typical Western diet and provide the greatest and least expensive source of energy. Carbohydrates must be digested to monosaccha-rides before absorption. The Diet Contains Both Digestible...

The Resting Membrane Potential

Electrochemical Gradient

The different passive and active transport systems are coordinated in a living cell to maintain intracellular ions and other solutes at concentrations compatible with life. Consequently, the cell does not equilibrate with the extracellular fluid, but rather exists in a steady state with the extracellular solution. For example, intracellular Na concentration 10 mmol L in a muscle cell is much lower than extracellular Na concentration 140 mmol L , so Na enters the cell by passive transport...

The Liver Plays an Important Role in the Metabolism of Lipids

Lipoprotein Catabolism

The liver plays a pivotal role in lipid metabolism Fig. 28.4 . It takes up free fatty acids and lipoproteins complexes of lipid and protein from the plasma. Lipid is circulated in the plasma as lipoproteins because lipid and water are not mis- The Metabolism of Monosaccharides. Monosaccharides are first phosphorylated by a reaction catalyzed by the enzyme hexokinase. In the liver but not in the muscle , there is a specific enzyme glucokinase for the phosphorylation of glucose to form glucose...

The Enterohepatic Circulation Recycles Bile Salts Between the Small Intestine and the Liver

Cholesterol Enterohepatic Circulation

The enterohepatic circulation of bile salts is the recycling of bile salts between the small intestine and the liver. The total amount of bile acids in the body, primary or secondary, conjugated or free, at any time is defined as the total bile acid pool. In healthy people, the bile acid pool ranges from 2 to 4 g. The enterohepatic circulation of bile acids in this pool is physiologically extremely important. By cycling several times during a meal, a relatively small bile acid pool can provide...

Stria Medullaris

Brain Area Pituitary Locus Cingulate

Patients with life-threatening, intractable epileptic seizures were treated in the past by surgical commissurotomy or cutting of the corpus callosum see Fig. 7.7 . This procedure effectively cut off most of the neuronal communication between the left and right hemispheres and vastly improved patient status because seizure activity no longer spread back and forth between the hemispheres. There was a remarkable absence of overt signs of disability following commissurotomy patients retained their...

The Primary Neurotransmitters of the ANS Are Acetylcholine and Norepinephrine

Paravertebral Nerve Block Anatomy

In the somatic nervous system, neurotransmitter is released from specialized nerve endings that make intimate contact with the target structure. The mammalian motor endplate, with one nerve terminal to one skeletal muscle fiber, illustrates this principle. This arrangement contrasts with the ANS, where postganglionic axons terminate in varicosities, swellings enriched in synaptic vesicles, which release the transmitter into the extracellular space surrounding the effector cells see Fig. 6.1 ....

The Balance Between Heat Production And Heat Loss

Heat Production Skeletal Muscle

All animals exchange energy with the environment. Some energy is exchanged as mechanical work, but most is exchanged as heat Fig. 29.4 . Heat is exchanged by conduction, convection, and radiation and as latent heat through evaporation or rarely condensation of water. If the sum of energy production and energy gain from the environment does not equal energy loss, the extra heat is stored in, or lost from, the body. This relationship is summarized in the heat balance equation Exchange of energy...

Hypothalamic Pituitary Adrenal Axis

Hypothalamus Pituitary Adrenal Gland

The main actions of corticotropin-releasing hormone CRH on a corticotroph. CRH binds to membrane receptors that are coupled to adenylyl cyclase AC by stimulatory G proteins Gs . Adenylyl cyclase is stimulated, and cAMP rises in the cell. cAMP activates protein kinase A PKA , which then phosphorylates proteins P proteins involved in stimulating ACTH secretion and the expression of the POMC gene. The main actions of corticotropin-releasing hormone CRH on a corticotroph. CRH binds to membrane...

Female Infertility Is Caused by Endocrine Malfunction and Abnormalities in the Reproductive Tract

The diagnosis and treatment of amenorrhea present a challenging problem. The amenorrhea must first be classified as primary or secondary, and menopause, pregnancy, and lactation must be excluded. The next step is to determine whether the disorder originates in one of the following areas the hypothalamus and central nervous system, the anterior pituitary, the ovary, and or the reproductive tract. Several treatments can alleviate infertility problems,- for example, some success has been achieved...

The Islets of Langerhans Are the Functional Units of the Endocrine Pancreas

Islet Langerhans

The islets of Langerhans contain from a few hundred to several thousand hormone-secreting endocrine cells. The islets are found throughout the pancreas but are most abundant in the tail region of the gland. The human pancreas contains, on average, about 1 million islets, which vary in size from 50 to 300 xm in diameter. Each islet is separated from the surrounding acinar tissue by a connective tissue sheath. Islets are composed of four hormone-producing cell types insulin-secreting beta cells,...

Exercise Plays a Role in Calcium Homeostasis

Bone Mineral Density Exercise Graph

Skeletal muscle contraction applies force to bone. Because the architecture of bone remodeling involves osteoblast and osteoclast activation in response to loading and unloading, physical activity is a major site-specific influence on bone mineral density and geometry. Repetitive physical activity can create excessive strain, leading to inefficiency in bone remodeling and stress fracture,- however, extreme inactivity allows osteoclast dominance and bone loss. The forces applied to bone during...

Hensen S Stripe

Ligament The Middle Ear

Modified from Gulick WL, Gescheider GA, Frisina RD. Hearing Physiological Acoustics, Neural Coding, and Psychoacoustics. New York Oxford University Press, 1989, Table 2.2, p. 51. Modified from Gulick WL, Gescheider GA, Frisina RD. Hearing Physiological Acoustics, Neural Coding, and Psychoacoustics. New York Oxford University Press, 1989, Table 2.2, p. 51. Vestibule Vestibular nerve Facial nerve Vestibule Vestibular nerve Facial nerve The overall structure of the human ear. The structures of the...

Trauma Exercise and Hypoglycemia Stimulate the Medulla to Release Catecholamines

Epinephrine and some NE are released from chromaffin cells by the fusion of secretory granules with the plasma membrane. The contents of the granules are extruded into the interstitial fluid. The catecholamines diffuse into capillaries and are transported in the bloodstream. Neural stimulation of the cholinergic preganglionic fibers that innervate chromaffin cells triggers the secretion of catecholamines. Stimuli such as injury, anger, anxiety, pain, cold, strenuous exercise, and hypoglycemia...

The Hypothalamus Regulates Eating Behavior

Arcuate Nucleus Third Ventricle

Classically, the hypothalamus has been considered a grouping of regulatory centers governing homeostasis. With respect to eating, the ventromedial nucleus of the hypothalamus serves as a satiety center and the lateral hypo-thalamic area serves as a feeding center. Together, these areas coordinate the processes that govern eating behavior and the subjective perception of satiety. These hypothalamic areas also influence the secretion of hormones, partic- Paraventricular nucleus Anterior...

Afferent Muscle Innervation Provides Feedback for Motor Control

Nuclear Bag Fiber

The muscles, joints, and ligaments are innervated with sensory receptors that inform the central nervous system about body position and muscle activity. Skeletal muscles contain muscle spindles, Golgi tendon organs, free nerve endings, and some Pacinian corpuscles. Joints contain Ruffini endings and Pacinian corpuscles,- joint capsules contain nerve endings,- ligaments contain Golgi tendon-like organs. Together, these are the proprioceptors, providing sensation from the deep somatic structures....

Lung Volumes Affect Pulmonary Vascular Resistance

How Measure Pulmonary Blood Pressure

Pulmonary vascular resistance is also significantly affected by lung volume. Because pulmonary capillaries have little , Measuring pulmonary wedge pressure. A catheter is threaded through a peripheral vein in the systemic circulation, through the right heart, and into the pulmonary artery. The wedged catheter temporarily occludes blood flow in a part of the vascular bed. The wedge pressure is a measure of downstream pressure, which is pulmonary venous pressure. Pulmonary venous pressure...

The Spinal Cord Mediates Reflex Activity

Homonymous Motor Neurons

The spinal cord contains neural circuitry to generate reflexes, stereotypical actions produced in response to a peripherally applied stimulus. One function of a reflex is to generate a rapid response. A familiar example is the rapid, involuntary withdrawal of a hand after touching a danger ously hot object well before the heat or pain is perceived. This type of reflex protects the organism before higher CNS levels identify the problem. Some reflexes are simple, others much more complex. Even...