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)....

Thyroid Hormone Deficiency Causes Nervous and Metabolic Disorders

Thyroid hormone deficiency in humans has a variety of causes. For example, iodide deficiency may result in a reduction in thyroid hormone production. Autoimmune diseases, such as Hashimoto's disease, impair thyroid hormone synthesis (see Clinical Focus Box 33.1). Other causes of thyroid hormone deficiency include heritable diseases that affect certain steps in the biosynthesis of thyroid hormones and hypothalamic or pituitary diseases that interfere with TRH or TSH secretion. Obviously,...

The Mechanism Of Thyroid Hormone Action

Most cells of the body are targets for the action of thyroid hormones. The sensitivity or responsiveness of a particular cell to thyroid hormones correlates to some degree with the number of receptors for these hormones. The cells of the CNS appear to be an exception. As is discussed later, the thyroid hormones play an important role in CNS development during fetal and neonatal life, and developing nerve cells in the brain are important targets for thyroid hormones. In the adult, however, brain...

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...

Synthesis Secretion And Metabolism Of The Thyroid Hormones

T4 and T3 are not directly synthesized by the thyroid follicle in their final form. Instead, they are formed by the chemical modification of tyrosine residues in the peptide structure of thyroglobulin as it is secreted by the follicular cells into the lumen of the follicle. Therefore, the T4 and T3 formed by this chemical modification are actually part of the amino acid sequence of thyroglobulin. The high concentration of thyroglobulin in the colloid provides a large reservoir of stored thyroid...

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

Glucose And Insulin Response Exercise

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...

Thyroid Hormones Regulate the Basal Energy Economy of the Body

When the body is at rest, about half of the ATP produced by its cells is used to drive energy-requiring membrane transport processes. The remainder is used in involuntary muscular activity, such as respiratory movements, peristalsis, contraction of the heart, and in many metabolic reactions requiring ATP, such as protein synthesis. The energy required to do this work is eventually released as body heat. Basal Oxygen Consumption and Body Heat Production. The major site of ATP production is the...

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...

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...

Thyroid Hormones Are Essential for Development of the Central Nervous System

The human brain undergoes its most active phase of growth during the last 6 months of fetal life and the first 6 months of postnatal life. During the second trimester of pregnancy, the multiplication of neuroblasts in the fetal brain reaches a peak and then declines. As pregnancy progresses and the rate of neuroblast division drops, neuroblasts differentiate into neurons and begin the process of synapse formation that extends into postnatal life. Thyroid hormones first appear in the fetal blood...

Memory and Learning Require the Cerebral Cortex and Limbic System

Septal Nucleus Basal Forebrain

Memory and learning are inextricably linked because part of the learning process involves the assimilation of new information and its commitment to memory. The most likely sites of learning in the human brain are the large association areas of the cerebral cortex, in coordination with subcortical structures deep in the temporal lobe, including the hippocampus and amygdala. The association areas draw on sensory information received from the primary visual, auditory, somatic sensory, and...

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...

Substantial Amounts of Calcium and Phosphate Enter and Leave Bone Each

Bone Growth Osteoid Mineralized Bone

Although bone may be considered as being a relatively inert material, it is active metabolically. Considerable amounts of calcium and phosphate both enter and exit bone each day, and these processes are hormonally controlled. Composition of Bone. Mature bone can be simply described as inorganic mineral deposited on an organic framework. The mineral portion of bone is composed largely of calcium phosphate in the form of hydroxyapatite crystals, which have the general chemical formula Ca10 PO4 6...

TSH Regulates the Function of the Thyroid Gland

Trh Ca2 Dag

The thyroid gland is composed of aggregates of follicles, which are formed from a single layer of cells. The follicular cells produce and secrete thyroxine T4 and triiodothyronine T3 , thyroid hormones that are iodinated derivatives of the amino acid tyrosine. The thyroid hormones act on many cells by changing the expression of certain genes, changing the capacity of their target cells to produce particular proteins. These changes are thought to bring about the important actions of the thyroid...

Enterocytes Secrete Chylomicrons and Very Low Density Lipoproteins

Chylomicrons Size

The reassembled triglycerides, lecithin, cholesterol, and cholesterol esters are then packaged into lipoproteins and exported from the enterocytes. The intestine produces two major classes of lipoproteins chylomicrons and very low density lipoproteins VLDLs . Both are triglyceride-rich lipoproteins with densities less than 1.006 g mL. Chylomicrons are made exclusively by the small intestine, and their primary function is to transport the large amount of dietary fat absorbed by the small...

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

Lipid Absorption Micel

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...

Info

Smooth Tetanus

Focal dystonias are neuromuscular disorders characterized by involuntary and repetitive or sustained skeletal muscle contractions that cause twisting, turning, or squeezing movements in a body part. Abnormal postures and considerable pain, as well as physical impairment, often result. Usually the abnormal contraction is limited to a small and specific region of muscles, hence, the term focal by itself . Dystonia means faulty contraction. Spasmodic torticollis and cervical dystonia involving...

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...

Androgens Are Responsible for Secondary Sex Characteristics and the Masculine Phenotype

Androgens effect changes in hair distribution, skin texture, pitch of the voice, bone growth, and muscle development. Hair is classified by its sensitivity to androgens into nonsexual eyebrows and extremities ambisexual axilla , which is responsive to low levels of androgens and sexual face, chest, upper pubic triangle , which is responsive only to high androgen levels. Hair follicles metabolize testosterone to DHT or androstenedione. Androgens stimulate the growth of facial, chest, and...

Hypothalamicpituitary Axis

Median Eminence Definition

The human pituitary is composed of two morphologically and functionally distinct glands connected to the hypothalamus. The pituitary gland or hypophysis is located at the base of the brain and is connected to the hypothalamus by a stalk. It sits in a depression in the sphenoid bone of the skull called the sella turcica. The two morphologically and functionally distinct glands comprising the human pituitary are the adenohypophysis and the neurohypophysis Fig. 32.1 . The adenohypophysis consists...

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,...

Thyroxine and Triiodothyronine Are Synthesized and Secreted by the Thyroid Follicle

The Thyroid Spherical Follicles

The lobes of the thyroid gland consist of aggregates of many spherical follicles, lined by a single layer of epithelial cells Fig. 33.1 . The apical membranes of the follicular A cross-sectional view through a portion of the human thyroid gland. A cross-sectional view through a portion of the human thyroid gland. cells, which face the lumen, are covered with microvilli. Pseudopods formed from the apical membrane extend into the lumen. The lateral membranes of the follicular cells are connected...

Hensen S Stripe

Structure Ear Facial Nerve

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...

Thyroid Hormone Synthesis

Oedogonium

Thyroid hormone synthesis and secretion. See text for details. DIT, diiodotyrosine MIT, monoiodotyrosine. Thyroid hormone synthesis and secretion. See text for details. DIT, diiodotyrosine MIT, monoiodotyrosine. licular cells, migrate toward the apical region of the stimulated cells. The lysosomes fuse with the colloid droplets and hydrolyze the thyroglobulin to its constituent amino acids. As a result, T4 and T3 and the other iodinated amino acids are released into the cytosol. Secretion of...

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...

The Indicator Dilution Method Measures Fluid Compartment Size

The indicator dilution method can be used to determine the size of body fluid compartments see Chapter 14 . A known amount of a substance the indicator , which should be confined to the compartment of interest, is administered. After allowing sufficient time for uniform distribution of the indicator throughout the compartment, a plasma sample is collected. The concentration of the indicator in the plasma at equilibrium is measured, and the distribution volume is calculated from this formula...

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

Lung Volume Laparoscopic

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...

Skeletal Muscle Action Potential

Action Potential Skeletal Muscle

Brane potential to change after a stimulus is applied is called the time constant or t, and its relationship to capacitance C and resistance R is defined by the following equation In the absence of an action potential, a stimulus applied to the neuronal membrane results in a local potential change that decreases with distance away from the point of stimulation. The voltage change at any point is a function of current and resistance as defined by Ohm's law. If a lig-and-gated channel opens...

The Spinal Cord Mediates Reflex Activity

Inverse Myotatic Reflex

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...

Cardiac Energy Consumption Is Required to Support External and Internal Cardiac Work

Cardiac energy consumption which is equivalent to cardiac oxygen consumption provides the energy for both external work and internal work. Most of the external work of the heart involves the ejection of blood from the ventricles into the aorta and pulmonary artery. The work of ejecting blood from the ventricles is the stroke work. Stroke work, strictly speaking, is equal to the product of the volume of blood ejected stroke volume, SV and the pressure against which the blood is ejected aortic...