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Active Immunity а this form of immunity develops through its own production of antibodies in response to medications available in mexico cheap arava 10mg free shipping exposure to treatment zoster ophthalmicus buy arava 10mg overnight delivery an antigen medicine 031 order arava us, pathogen, or vaccine. Fc Fragment а this fragment is constant, has a carbohydrate side-chain, is complement binding (IgG and IgM only), and has a carboxy terminal. When this occurs, the virus cannot infect a cell since the proper genetic materials for this function are absent. As this occurs, severe organ dysfunction ensues, causing damage to the liver, skin, mucosa, and gastrointestinal tract. Hyperacute Rejection: Occurs almost immediately after transplant, whereby preformed anti-donor antibodies cause a response. Chronic Rejection: Occurring months-years post-transplant, is caused by antibody-mediated vascular damage. When it comes to parasites and helminths, your strategy should be memorization of modes of transmission, signs and symptoms, and treatments. Aureus (fast onset, fast alleviation) Reheated rice а Bacillus Cereus Reheated meat а Clostridium Perfringens Seafood а Vibrio Parahemolyticus Improperly canned foods а Clostridium Botulinum (watch for bulging can tops) Undercooked meat а E. Strep Pyogenes а Erythrogenic toxin (superantigen) causes rash and scarlet fever, while streptolysin O (hemolysin) causes rheumatic fever. Endotoxins cause a wide range of problems through the activation of macrophages and the complement pathway. Toxin-Mediated Includes toxic-shock syndrome, scalded skin syndrome, and rapid-onset food poisoning. Difficile а produces a cytotoxin (exotoxin) that kills erythrocytes, and thus causes a pseudomembranous colitis. Perfringens а produces an -toxin that causes myonecrosis, gas gangrene, or hemolysis. Coli Vibrio (rice-water stools, highly voluminous) Rotavirus Giardia (foul-smelling) Cryptosporidium Treatment: Triple therapy: Omeprazole, clarithromycin, amoxicillin. Its most popular characteristic is that it produces a fruity-smelling blue-green pigment (due to pyocyanin). Vibrio Cholera causes a rice-water diarrhea by permanently activating the Gs protein. Bordetella Pertussis causes whooping cough by permanently disabling the Gi protein. Gardnerella a gram-variable rod that causes a green vaginal discharge that has a fishy smell, and has the pathognomonic "clue cells". Candida is a fungal infection that presents with a cottage-cheese like discharge that is sticky and will stick to the walls of the vagina. Lyme Disease caused by Borrelia Burgdorferi, which is transmitted through the Ixodes tick bite, which is a tick that lives on deer and mice. Cellulitis caused by Pasteurella Multicoda, which occurs through dog or cat bites. Tularemia caused by Francisella Tularensis, from a tick bite, seen in rabbits and deer. Brucellosis caused by Brucella species, and contamination occurs through infected dairy products and contact with animals. The plague caused by Yersinia pestis, transmitted through a flea bite found on rodents and wild dogs. This results in the Ghon complex, which is a calcified focus of infection usually in the lower segments of the lung. Beware of adverse neurological effects of Isoniazid, supplement with vitamin B6 pyridoxine. The other two types of spirochetes are Borrelia and Leptospira, which are stainable with light microscopy, whereas treponema is visualized only with dark-field microscopy. This occurs at high frequency and is responsible for worldwide illnesses (pandemics). Complementation а occurs when one functional virus helps another non- functional virus become functional. Papovavirus is circular/supercoiled, and the Hepadna virus is circular/incomplete. Genetic shift is very important because it creates new viral pathogens, and is responsible for the emergence of new viruses. Transmitted congenitally, through sexual contact, through saliva, and through transfusion. After confirmation, a viral load can be done to measure the quantity of the virus in the blood, which allows you to measure the effect of medical treatment. There is a wide range of routes of infection, there is a wide range of symptoms and prognosis, which can range from self-limited diseases to cirrhosis and death. Hep B is usually self-limited, but can progress and cause cirrhosis, hepatic failure, and death. Transmission is usually sexual, through sharing dirty needles (parenteral), and from the mother to fetus (vertical transmission). Aspiration а Anaerobic oral flora Neonatal а Up to the first 6 weeks of life Group B strep and E. The most common symptoms are painful urination, frequency, urgency, and suprapubic pain. Most common in women because they have a short distance from the outside of the urethra to the bladder. Patient presents most commonly with nuchal rigidity, high fever, and altered mental status. The most common causes per age group are the following: In newborns up to 6 months а E. There is often symptoms such as cervical motion tenderness, vaginal discharge, and even tubo-ovarian abscess. It can cause a wide variety of conditions, and can be seen both superficially (on the skin), and systemically (anywhere else). Tinea Corporis "Ringworm", is a skin infection of the arms and legs most commonly, however it can occur anywhere. The classic appearance is a circular rash that clears centrally with elevated edges. Tinea Versicolor Is a rash of the trunk and proximal extremities, caused by Malassezia Furfur. Classic presentation is hypopigmentation of the skin with sharp borders and fine scaling. Tinea Nigra Affects the keratinized layer of the skin, producing brown pigments. Is a very heavily encapsulated yeast that is found in soil and in pigeon droppings. Heavily encapsulated yeast (~5-10um in diameter) Aspergillus Fumigatus Causes a "fungus ball" cavity in the lungs. It causes local ulcerations in addition to nodules that follow the lymphatic drainage. Focus should be made on the following: Mechanisms of Action, clinical use/applications, side effects.
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Carotenoids are found in yellow treatment atrial fibrillation buy arava 10 mg low cost, orange medicine education discount arava american express, and red plant compounds and green leafy vegetables treatment zenkers diverticulum cheap arava 20 mg without a prescription. In the intestine, the carotenoid precursors break down into retinaldehyde molecules, which in turn can be reduced to retinol by hepatic aldehyde reductase and stored in the liver. Less than one third of ingested carotenoid is absorbed by the body, and a small amount of that is eventually converted to retinol. Beta-carotene is the major carotenid in the liver, adrenal glands, kidney, ovary, and adipose tissue, whereas lycopene is predominantly found in the testes. Oxycarotenoids, like zeaxanthin and lutein, are present in the macula in the virtual absence of beta-carotene. The main biological functions of vitamin A are to promote good vision by maintaining photoreceptor pigment, ensure normal cellular differentiation and integrity, maintain an efficient immune function, and prevent squamous metaplasia of the epithelium. By virtue of their antioxidant activity, carotenoids have been shown to limit oxidative damage from free radical reactions and contribute to the protection of membranes from lipid peroxidation. Worldwide, it is the third most common nutritional deficiency, causing blindness, ill health, and mortality in over 100,000 children annually. In developed countries, deficiency occurs very rarely, particularly in the elderly. Prolonged periods of diminished intake is necessary for a deficiency state to develop. Deficiency results in: · Night blindness due to loss of rhodopsin in rods, complete blindness due to loss of iodopsin in cones, and xerophthalmia. Xerodermia, follicular hyperkeratosis (phrynoderma), squamous metaplasia of hair follicles, and possibly impaired wound healing. Increased susceptibility to and severity of infections due to impaired immunity secondary to decreased natural killer cell number and function. Increased susceptibility to pneumonia and bronchitis is further exacerbated by squamous metaplasia of the respiratory epithelium. Some studies have indicated increased absorption (Hollander and Morgan 1979) and decreased clearance (Krasinski et al. Elderly persons taking vitamin A supplements have been found to have higher levels of circulating retinyl esters, the toxic indicator, than elderly not taking supplements (Krasinski et al. Impaired renal and hepatic function increased risk of toxicity (Chernoff 2005), whereas excess vitamin E imparts some protection. Symptoms of toxicity include nausea, vomiting, anorexia, headaches, dizziness, drowsiness, and irritability. Chronic toxicity presents with anorexia, alopecia, fatigue, hypothyroidism, bone and muscle pain, hepatosplenomegaly, and increased intracranial pressure. Hypervitaminosis A in the elderly also presents with bone pain, bone inflammation, and hypercalcemia. Vitamin A enhances the activity of vitamin D and parathyroid hormone and a negative calcium balance may occur. Increased osteoclastic activity and decreased 146 Geriatric Nutrition bone mineral density at the femoral neck and lumbar spine have been documented (Kneissel et al. Dietary intake of 1500 µg or more per day is associated with osteoporosis and an increased risk of hip fractures (Melhus et al. These findings were only noted with excess intake of preformed vitamin A (retinol) and not beta-carotene. Beta-carotein is also widely considered to be nontoxic, and humans tolerated high doses without apparent harm. There is no evidence that conversion of beta-carotene to vitamin A contributes to toxicity of the latter, even when beta-carotene is ingested in large amounts. The only undesirable effect of high beta-carotene intake is a yellowish discoloration of the skin, or carotehnemia, which occurs only at extremely high intake (Mathews-Roth 1986). It can be synthesized in the human body, and therefore functions more as a pro-hormone. Vitamin D is a general term referring to the final biologically active product as well as its numerous precursors. Vitamin D2 is formed by the ultraviolet irradiation of ergosterol and is found in plants, while vitamin D3 is primarily found in animal products. It was previously believed that both forms have similar metabolism and biological function, but Armas et al. Dietary sources of vitamin D3 include egg yolks, fish liver oils, and fortified foods. The major source, however, is synthesized in the skin by converting 7-dehydrocholesterol to vitamin D3 with adequate sunlight exposure. Vitamin D from either source is bound to vitamin D-binding protein and transported to the liver, where it is hydroxylated by 25-vitamin D-hydroxylase to 25-hydroxy-vitamin D, or calcidiol. Serum levels of calcitriol, however, do not necessarily reflect total body stores of the vitamin due to the relatively short half-life of 4 to 6 hours. Calcidiol, on the other hand, has a half-life of approximately 3 weeks (Thomas and Demay 2000) and is a better measure of vitamin D status (Johnson et al. Up to 25% of communitydwelling elderly may have vitamin D deficiency, and the prevalence can be as high as 80% in residents of long-term-care facilities. Several changes associated with aging result in age being a risk factor for vitamin D deficiency. Decreased exposure to sunlight and decreased amounts of 7-dehydrocholesterol levels in the aging skin Vitamin Disorders 147 deprive the elderly of the major source of vitamin D that younger adults enjoy. In the absence of adequate photoconversion, dietary intake becomes a much more crucial source of vitamin D. This, however, occurs at a time when dairy products and other vitamin D-rich foods constitute a declining part of the typical geriatric diet. Finally, several medications disrupt vitamin D absorption, activation, or function. Most notable are anticonvulsants, rifampin, ketoconazole, primidone, and many other drugs that can impair hydroxylation or accelerate elimination by activating the cytochrome P-450 system. Concurrent calcium supplementation is advised since the typical adult diet does not meet calcium requirements (Kamel and Hajjar 2003). Biochemical manifestations of vitamin D deficiency include hypocalcemia, hypophosphatemia, and elevated alkaline phosphatase. With prolonged hypocalcemia, secondary hyperparathyroidism may develop, which further decreases phosphorus levels and promotes bone resorption by stimulating osteoclasts. Clinical features of these changes include accelerated osteoporosis and an increased risk of vertebral and long bone fracture. Vitamin D deficiency may also present with any of the symptoms of hypocalcemia, such as neuromuscular irritability, neuropathy, hyperesthesia, and proximal myopathy or pain. The benefits of supplementing vitamin D in the elderly have been documented in many studies.
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Presbycusis symptoms ms women buy arava online from canada, the gradual hearing loss associated with aging symptoms bronchitis purchase generic arava pills, affects more than one-third of those over 75 and is probably due to medicine the 1975 buy discount arava 10mg on-line gradual cumulative loss of hair cells and neurons. In most cases, hearing loss is a multifactorial disorder caused by both genetic and environmental factors. Deafness can be divided into two major categories: conductive (or conduction) and sensorineural hearing loss. Conductive deafness refers to impaired sound transmission in the external or middle ear and impacts all sound frequencies. Sensorineural deafness is most commonly the result of loss of cochlear hair cells but can also be due to problems with the eighth cranial nerve or within central auditory pathways. Aminoglycoside antibiotics such as streptomycin and gentamicin obstruct the mechanosensitive channels in the stereocilia of hair cells and can cause the cells to degenerate, producing sensorineural hearing loss and abnormal vestibular function. Damage to the outer hair cells by prolonged exposure to noise is associated with hearing loss. Other causes include tumors of the eighth cranial nerve and cerebellopontine angle and vascular damage in the medulla. Conduction and sensorineural deafness can be differentiated by simple tests with a tuning fork. Three of these tests, named for the individuals who developed them, are outlined in Table 131. The Weber and Schwabach tests demonstrate the important masking effect of environmental noise on the auditory threshold. The detectable time difference, which can be as little as 20 s, is said to be the most important factor at frequencies below 3000 Hz and the loudness difference the most important at frequencies above 3000 Hz. Neurons in the auditory cortex that receive input from both ears respond maximally or minimally when the time of arrival of a stimulus at one ear is delayed by a fixed period relative to the time of arrival at the other ear. Sounds coming from directly in front of the individual differ in quality from those coming from behind because each pinna (the visible portion of the exterior ear) is turned slightly forward. In addition, reflections of the sound waves from the pinnal surface change as sounds move up or down, and the change in the sound waves is the primary factor in locating sounds in the vertical plane. The vestibular nuclei are primarily concerned with maintaining the position of the head in space. The tracts that descend from these nuclei mediate head-on-neck and head-on-body adjustments. This type of hearing loss is a monogenic disorder with an autosomal dominant, autosomal recessive, X-linked, or mitochondrial mode of inheritance. Monogenic forms of deafness can be defined as syndromic (hearing loss associated with other abnormalities) or nonsyndromic (only hearing loss). Nonsyndromic deafness due to genetic mutations can first appear in adults rather than in children and may account for many of the 16% of all adults who have significant hearing impairment. It is now estimated that the products of 100 or more genes are essential for normal hearing, and deafness loci have been described in all but 5 of the 24 human chromosomes. The most common mutation leading to congenital hearing loss is that of the protein connexin 26. Deafness is also associated with mutant forms of -tectin, one of the major proteins in the tectorial membrane. An example of syndromic deafness is Pendred syndrome, in which a mutant sulfate transport protein causes deafness and goiter. Mutations of the membrane protein barttin can cause deafness as well as the renal manifestations of Bartter syndrome. Each vestibular nerve terminates in the ipsilateral four-part vestibular nucleus and in the flocculonodular lobe of the cerebellum (Figure 1312). Fibers from the semicircular canals end primarily in the superior and medial divisions of the vestibular nucleus and project mainly to nuclei controlling eye movement. Fibers from the utricle and saccule end predominantly in the lateral division (Deiters nucleus), which projects to the spinal cord. They also end on neurons that project to the cerebellum and the reticular formation. The vestibular nuclei also project to the thalamus and from there to two parts of the primary somatosensory cortex. The ascending connections to cranial nerve nuclei are largely concerned with eye movements. The endolymph, because of its inertia, is displaced in a direction opposite to the direction of rotation. When a constant speed of rotation is reached, the fluid spins at the same rate as the body and the cupula swings back into the upright position. When rotation is stopped, deceleration produces displacement of the endolymph in the direction of the rotation, and the cupula is deformed in a direction opposite to that during acceleration. Rinne Base of vibrating tuning fork placed on mastoid process until subject no longer hears it, then held in air next to ear. Conduction deafness (one ear) Sound louder in diseased ear because masking effect of environmental noise is absent on diseased side. Sensorineural deafness (one ear) Vibration heard in air after bone conduction is over, as long as nerve deafness is partial. It is actually a reflex that maintains visual fixation on stationary points while the body rotates, although it is not initiated by visual impulses and is present in blind individuals. When the limit of this movement is reached, the eyes quickly snap back to a new fixation point and then again move slowly in the other direction. The slow component is initiated by impulses from the vestibular labyrinths; the quick component is triggered by a center in the brain stem. Nystagmus is frequently horizontal (ie, the eyes move in the horizontal plane), but it can also be vertical (when the head is tipped sidewise during rotation) or rotatory (when the head is tipped forward). By convention, the direction of eye movement in nystagmus is identified by the direction of the quick component. The direction of the quick component during rotation is the same as that of the rotation, but the postrotatory nystagmus that occurs owing to displacement of the cupula when rotation is stopped is in the opposite direction. Nystagmus can persist for hours at rest in patients with acute temporal bone fracture affecting semicircular canals or after damage to the flocculonodular lobe or midline structures such as the fastigial nucleus. Nystagmus can be used as a diagnostic indicator of the integrity of the vestibular system. The semicircular canals are stimulated by instilling warm (40 °C) or cold (30 °C) water into the external auditory meatus. The temperature difference sets up convection currents in the endolymph, with consequent motion of the cupula. In normal subjects, warm water causes nystagmus that bears toward the stimulus, whereas cold water induces nystagmus that bears toward the opposite ear. In the case of a unilateral lesion in the vestibular pathway, nystagmus is reduced or absent on the side of the lesion. To avoid nystagmus, vertigo, and nausea when irrigating the ear canals in the treatment of ear infections, it is important to be sure that the fluid used is at body temperature. Average time course of impulse discharge from the ampulla of two semicircular canals during rotational acceleration, steady rotation, and deceleration.
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The first day of the cycle is the first day of blood flow (day 0) known as menstruation medicine klonopin safe arava 20 mg. The drop in hormones also causes the sloughing off of the inner lining of the uterus by a series of muscle contractions of the uterus Sequences of menstrual cycle: · Follicle stage ovulation corpus luteum menstruation · Fertilization During intercourse 100s of millions of sperm are released into the vagina medications qd cheap arava 10mg line. This is to medications for high blood pressure discount 10mg arava fast delivery ensure that some sperm will survive and fertilize the egg Sperm swim through the cervix, up through the uterus, and in to the oviducts If there is an egg moving down the oviduct it may be fertilized by the sperm. If the fertilized egg implants in the wall of the uterus the corpus luetum will release large amounts of progesterone Fertilization facts · Mitosis (cell division) of the fertilized egg occurs in the oviduct (fallopian tube) Sperm can live in the female reproductive system for 72 hours. Humans have 46 Chromosomes 23 egg + 23 sperm = 46 new complete set Differentiation: Embryonic cells will use different portions of their genetic information to become different cells of the body. If an X chromosome is present the baby is a girl; if a Y chromosome is carried by the sperm instead, the baby is a boy. Twins Occasionally two eggs are released by the ovary and fertilized by a different sperm. This results in fraternal twins who are different in appearance and may be of different sexes because their genes form from two eggs and two sperm cells. Rarely, one embryo splits into two and both cells develop separately, as identical twins, similar in appearance. Embryo and fluid are enclosed in two membranes, an inner amnion and an outer chorion. Carbon dioxide (waste product from cellular respiration) passes through the placenta from the blood of the fetus to the blood of the mother. A pathogen passed from mother to fetus could cause an infection in the fetus the German measles is a virus which can cross the placenta from mother to fetus. Body development Exposure to toxins (smoking,pesticides, other chemicals) and alcohol during early stages of pregnancy can cause birth defects because essential organs form during early development. Development of human: Fertilized egg tissues organs fetus #1 Oviduct or Fallopian tube: fertilization occurs here #2 Uterine muscles: contracts and pushes baby out during labor. Estrogen will stimulate the production of extra blood vessels here #3 Uterus: Embryo develops into fetus, influenced by progesterone & estrogen during pregnancy. Carbon dioxide & other waste products (excretion) exchange from baby to mom Blood systems of mom and baby are separate, but certain materials can pass from one another through the placenta by diffusion. Techniques include In Vitro Fertilization Artificial Insemination Gamete Intra-Fallopian Transfer And many more What is Infertility? Infertility affects about 15% of couples in the United States Factors Affecting Conception Production of healthy sperm Healthy eggs by the woman Unblocked fallopian tubes the ability for the sperm to fertilize the egg the ability for the embryo to implant in the uterus Causes of Infertility in Women the older a woman is the higher her chances of becoming infertile. Ovulation disorder Blocked fallopian tubes caused by a pelvic inflammatory disease or endometriosis (a condition that causes adhesions and cysts) Adhesions is scar tissue Causes of Infertility in Men Azoospermia-lack of sperm production Inability to ejaculate normally Varicocele- veins in the scrotum are enlarged which can heat the inside of the scrotum and can affect sperm production. This allows a higher chance of pregnancy Left-over Embryos Typically, during fertility treatments, women may store fertilized eggs, embryos, as part of their treatment. Kept frozen for unanticipated catastrophe A kind of immortality Many major fertility centers have thousands of these-10,000 per year nationally No federal agency oversees this Sometimes embryos are donated to infertile couples, but legal issues about parental rights persist. Surrogacy · Surrogacy occurs when I woman agrees to carry to term the fetus for another person. That fetus may be from the egg and sperm of the couple who want to raise the child or it may be donor eggs or donor sperm. Symptoms of herpes can be treated by antiviral drugs, but the infection cannot be cured. Syphilis is a bacterially caused infection, and can, if left untreated, cause serious symptoms and death. Infectious individuals may appear symptom-free for years after infection Ecology · Ecology is the study of interactions among organisms and between organisms and their environment. Population are groups of individuals that belong to the same species and live in the same area. Ex: All the goldfish in a tank or all the deer in the park Communities are assemblages of the different populations that live together in a defined area. For a stable ecosystem: there must be interrelationships & interdependencies among organisms Organisms within an ecosystem depend on the activities of biological catalysts Biome is a group of ecosystems that have the same climate and similar dominant communities. The arrows indicate energy being transferred from one organism to the next as it is being eaten. The grass gets eaten by the mouse, and the mouse gets eaten by the snake & hawk Energy Flow · Sunlight is the main source of energy for life on Earth. Some types of organisms rely on the energy stored in inorganic chemical compounds. Autotrophs (producers) use energy from the sun to change inorganic compounds into complex organic molecules. Energy Flow: Autotrophs-Synthesize their own food from inorganic compounds (carbon dioxide and water) and energy from the sun the best known autotrophs (plants) are those that harness the power of the sun through photosynthesis. This is performed by several types of bacteria Producers = Autotrophs · Make their own food through photosynthesis. Examples: cows, mice, snails, rabbits · Carnivores obtain energy by eating animals. Commensalism: One organism benefits and the other is not harmed Barnacles and Whales Barnacles need a place to anchor. Some barnacles hitch a ride on unsuspecting whales who deliver them to a food source. Mutualism: both organisms benefit · Nitrogen fixing bacteria live in nodules on the roots of legumes. Bacteria create ammonia from nitrogen in air, which is used by the plant to create amino acids and nucleotides. The bacteria synthesize(make) vitamins used by humans a nd receive nutrition from the digested food. Otters & Kelp: the otters help the kelp by eating the sea urchins which endanger it. Lichens is really 2 organisms: algae & fungus · the fungus needs food but cannot make it. Cleaner fish & Moray Eel · the cleaner fish eats parasites and food bits out of the inside of this moray eel. Parasitism: One organism benefits, the organism is harmed Bedbugs: · Bedbugs are small, nocturnal parasites that come out of hiding at night to feed on unsuspecting humans. Tapeworms: · the definitive host of the cucumber tapeworm is a dog or a cat (occasionally a human). Presence of parasites in an animal results in the inability of the host to maintain homeostasis. If 2 organisms occupy the same niche (environmental requirements) they will compete against each other for food, nesting sites, limited resources. They do not compete with each other for food because they occupy the same habitat but different niches. The shelf fungus absorbs materials from the tree, while the slug eats algae growing on the outside of the trunk Feeding Relationships · Energy flows through an ecosystem in one direction, from the sun or inorganic compounds to autotrophs (producers) and then to various heterotrophs (consumers) and finally to decomposers Food Chains are a series of steps in which organisms transfer energy by eating or being eaten. Food Chain · A food chain indicates the transfer of energy from producers through a series of organisms (consumers) which feed upon each other.
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The pumps establish ionic concentration gradients so that K is concentrated inside the cell and Na is concentrated outside the cell medicine during pregnancy generic arava 10 mg without a prescription. However symptoms you have worms order 20mg arava with amex, because the membrane is impermeable to medicine nausea discount 20 mg arava overnight delivery K, the potassium conductance, gK, equals zero. Potassium current flows only when the membrane has open potassium channels and therefore gK 0. In this condition, although there is a large potassium conductance, gK, there is no longer any net driving force on the K (Figure 4. Nonetheless, there can be no net Na current as long as the membrane is impermeable to Na. At the instant we change the ionic permeability of the membrane, gNa is high, and, as we discussed earlier, there is a large driving force pushing on Na. Simply by switching the dominant membrane permeability from K to Na, we were able to rapidly reverse the membrane potential. In theory, then, the rising phase of the action potential could be explained if, in response to depolarization of the membrane beyond threshold, membrane sodium channels opened. Simply assume that sodium channels quickly close and the potassium channels remain open, so the dominant membrane ion permeability switches back from Na to K. Our model for the ins and outs, ups and downs of the action potential in an idealized neuron is shown in Figure 4. The rising phase of the action potential is explained by an inward sodium current, and the falling phase is explained by an outward potassium current. The action potential therefore could be accounted for simply by the movement of ions through channels that are gated by changes in the membrane potential. If you understand this concept, you understand a lot about the ionic basis of the action potential. When the membrane is depolarized to threshold, there is a transient increase in gNa. And the increase in gNa must be brief in duration to account for the short duration of the action potential. Restoring the negative membrane potential would be further aided by a transient increase in gK during the falling phase, allowing K to leave the depolarized neuron faster. All one has to do is measure the sodium and potassium conductances of the membrane during the action potential. In practice, however, such a measurement proved to be quite difficult in real neurons. The key technical breakthrough came with a device called a voltage clamp, invented by the American physiologist Kenneth C. Cole and used in decisive experiments performed by Cambridge University physiologists Alan Hodgkin and Andrew Huxley around 1950. The voltage clamp enabled Hodgkin and Huxley to "clamp" the membrane potential of an axon at any value they chose. They could then deduce the changes in membrane conductance that occur at different membrane potentials by measuring the currents that flowed across the membrane. In an elegant series of experiments, Hodgkin and Huxley showed that the rising phase of the action potential was indeed caused by a transient increase in gNa and an influx of Na, and that the falling phase was associated with an increase in gK and an efflux of K. To account for the transient changes in gNa, Hodgkin and Huxley proposed the existence of sodium "gates" in the axonal membrane. They hypothesized that these gates are "activated" (opened) by depolarization above threshold and "inactivated" (closed and locked) when the membrane acquires a positive membrane potential. These gates are "deinactivated" (unlocked and enabled to be opened again) only after the membrane potential returns to a negative value. It is a tribute to Hodgkin and Huxley that their hypotheses about membrane gates came more than 20 years before the direct demonstration of voltage-gated channel proteins in the neuronal membrane. We have a new understanding of gated membrane channels, thanks to two more recent scientific breakthroughs. First, new molecular biological techniques have enabled neuroscientists to determine the detailed structure of these proteins. Second, new neurophysiological techniques have enabled neuroscientists to measure the ionic currents that pass through single channels. We will now explore the action potential from the perspective of these membrane ion channels. The protein forms a pore in the membrane that is highly selective to Na, and the pore is opened and closed by changes in membrane voltage. When the membrane is depolarized to threshold, however, the molecule twists into a configuration that allows the passage of Na through the pore (Figure 4. Like the potassium channel, the sodium channel has pore loops that are assembled into a selectivity filter. This filter makes the sodium channel twelve times more permeable to Na than it is to K. Apparently, the Na ions are stripped of most, but not all, of their associated water molecules as they pass into the channel. The retained water serves as a sort of molecular chaperone for the ion, and is necessary for the ion to pass the selectivity filter. Each domain consists of six alpha helices (represented by the blue and purple cylinders), which pass back and forth across the membrane. It has now been established that the voltage sensor resides in segment S4 of the molecule. In this segment, positively charged amino acid residues are regularly spaced along the coils of the helix. Thus, the entire segment can be forced to move by changing the membrane potential. Depolarization twists S4, and this conformational change in the molecule causes the gate to open. Research performed around 1980 at the Max Planck Institute in Goettingen, Germany, revealed the functional properties of the voltage-gated sodium channel. A new method was used, called the patch clamp, to study the ionic currents passing through individual ion channels (Box 4. The patch-clamp method entails sealing the tip of an electrode to a very small patch of neuronal membrane. This patch can then be torn away from the neuron, and the ionic currents across it can be measured as the membrane potential is clamped at any value the experimenter selects. With luck, the patch will contain only a single channel, and the behavior of this channel can be studied. Patch clamping enabled investigation of the functional properties of the voltage-gated sodium channel. Changing the membrane potential of a patch of axonal membrane from 80 to 65 mV has little effect on the voltage-gated sodium channels. They remain closed because depolarization of the membrane has not yet reached threshold. Changing the membrane potential from 65 to 40 mV, however, causes these channels to pop open. They cannot be opened again by depolarization until the membrane potential returns to a negative value near threshold.
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These changes are defined by sequential activation and inactivation of Na+ treatments cheap arava 10 mg otc, Ca2+ medications versed purchase arava 10mg visa, and K+ channels symptoms for strep throat purchase discount arava on-line. After repolarization to the resting potential, there is a slow depolarization that occurs due to a channel that can pass both Na+ and K+. As this "funny" current continues to depolarize the cell, Ca2+ channels are activated to rapidly depolarize the cell. The rate of spread is dependent on anatomical features, but also can be altered (to a certain extent) via neural input. Because of the contribution of ionic movement to cardiac muscle contraction, heart tissue is sensitive to ionic composition of the blood. Most serious are increases in [K+] that can produce severe cardiac abnormalities, including paralysis of the atria and ventricular arrhythmias. A) sinoatrial node B) atrial muscle cells C) bundle of His D) Purkinje fibers E) ventricular muscle cells 3. In second-degree heart block A) the ventricular rate is lower than the atrial rate. Currents caused by opening of which of the following channels contribute to the repolarization phase of the action potential of ventricular muscle fibers? In complete heart block A) fainting may occur because the atria are unable to pump blood into the ventricles. D) fainting may occur because of prolonged periods during which the ventricles fail to contract. Understand the pressure, volume, and flow changes that occur during the cardiac cycle. Delineate the ways by which cardiac output can be up-regulated in the setting of specific physiologic demands for increased oxygen supply to the tissues, such as exercise. Describe how the pumping action of the heart can be compromised in the setting of specific disease states. This is accomplished when the orderly depolarization process described in the previous chapter triggers a wave of contraction that spreads through the myocardium. In single muscle fibers, contraction starts just after depolarization and lasts until about 50 ms after repolarization is completed (see Figure 515). In this chapter, we will consider how these changes in contraction produce sequential changes in pressures and flows in the heart chambers and blood vessels, and thereby propel blood appropriately as needed by whole body demands for oxygen and nutrients. As an aside, it should be noted that the term systolic pressure in the vascular system refers to the peak pressure reached during systole, not the mean pressure; similarly, the diastolic pressure refers to the lowest pressure during diastole. The failure may involve primarily the right ventricle (cor pulmonale), but much more commonly it involves the larger, thicker left ventricle or both ventricles. In systolic failure, stroke volume is reduced because ventricular contraction is weak. This causes an increase in the end-systolic ventricular volume, so that the ejection fraction falls from 65% to as low as 20%. The initial response to failure is activation of the genes that cause cardiac myocytes to hypertrophy, and thickening of the ventricular wall (cardiac remodeling). The incomplete filling of the arterial system leads to increased discharge of the sympathetic nervous system and increased secretion of renin and aldosterone, so Na+ and water are retained. These responses are initially compensatory, but eventually the failure worsens and the ventricles dilate. In diastolic failure, the ejection fraction is initially maintained, but the elasticity of the myocardium is reduced so filling during diastole is reduced. This leads to inadequate stroke volume and the same cardiac remodeling and Na+ and water retention that occur in systolic failure. It should be noted that the inadequate cardiac output in failure may be relative rather than absolute. When a large arterior venous fistula is present, in thyrotoxicosis and in thiamine deficiency, cardiac output may be elevated in absolute terms but still be inadequate to meet the needs of the tissues (high-output failure). Treatment of congestive heart failure is aimed at improving cardiac contractility, treating the symptoms, and decreasing the load on the heart. The effects of aldosterone can be further reduced by administering aldosterone receptor blockers. Reducing venous tone with nitrates or hydralazine increases venous capacity so that the amount of blood returned to the heart is reduced, lowering the preload. Drugs that block -adrenergic receptors have been shown to decrease mortality and morbidity. Digitalis derivatives such as digoxin have classically been used to treat congestive heart failure because of their ability to increase intracellular Ca2+ and hence exert a positive inotropic effect, but they are now used in a secondary role to treat systolic dysfunction and slow the ventricular rate in patients with atrial fibrillation. Contraction of the atrial muscle narrows the orifices of the superior and inferior vena cava and pulmonary veins, and the inertia of the blood moving toward the heart tends to keep blood in it. However, despite these inhibitory influences, there is some regurgitation of blood into the veins. Ventricular muscle initially shortens relatively little, but intraventricular pressure rises sharply as the myocardium presses on the blood in the ventricle (Figure 312). This period of isovolumetric (isovolumic, isometric) ventricular contraction lasts about 0. When the aortic and pulmonary valves open, the phase of ventricular ejection begins. The intraventricular pressure rises to a maximum and then declines somewhat before ventricular systole ends. Peak pressures in the left and right ventricles are about 120 and 25 mm Hg, respectively. Late in systole, pressure in the aorta actually exceeds that in the left ventricle, but for a short period momentum keeps the blood moving forward. Thus, about 50 mL of blood remains in each ventricle at the end of systole (end-systolic ventricular volume), and the ejection fraction, the percent of the end-diastolic ventricular volume that is ejected with each stroke, is about 65%. It can be measured by injecting radionuclide-labeled red blood cells and imaging the cardiac blood pool at the end of diastole and the end of systole (equilibrium radionuclide angiocardiography), or by computed tomography. The direction in which the pressure difference favors flow is denoted by an arrow; note, however, that flow will not actually occur if valve prevents it. It ends when the momentum of the ejected blood is overcome and the aortic and pulmonary valves close, setting up transient vibrations in the blood and blood vessel walls. After the valves are closed, pressure continues to drop rapidly during the period of isovolumetric ventricular relaxation. However, the duration of systole is much more fixed than that of diastole, and when the heart rate is increased, diastole is shortened to a much greater degree. It is during diastole that the heart muscle rests, and coronary blood flow to the subendocardial portions of the left ventricle occurs only during diastole (see Chapter 34). At heart rates up to about 180, filling is adequate as long as there is ample venous return, and cardiac output per minute is increased by an increase in rate.
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However treatment of criminals cheap 20mg arava visa, acid inhibits the lipase symptoms right after conception arava 20 mg amex, and the lack of alkaline secretion from the pancreas also contributes by lowering the pH of the intestine contents symptoms wheat allergy generic 20 mg arava. Another cause of steatorrhea is defective reabsorption of bile salts in the distal ileum (see Chapter 29). They are of little quantitative significance for lipid digestion other than in the setting of pancreatic insufficiency, however. Most fat digestion therefore begins in the duodenum, pancreatic lipase being one of the most important enzymes involved. This enzyme hydrolyzes the 1- and 3-bonds of the triglycerides (triacylglycerols) with relative ease but acts on the 2bonds at a very low rate, so the principal products of its action are free fatty acids and 2-monoglycerides (2-monoacylglycerols). Its activity is facilitated when an amphipathic helix that covers the active site like a lid is bent back. Colipase is secreted in an inactive proform (Table 271) and is activated in the intestinal lumen by trypsin. This 100,000-kDa cholesterol esterase represents about 4% of the total protein in pancreatic juice. In adults, pancreatic lipase is 1060 times more active, but unlike pancreatic lipase, this bile salt-activated lipase catalyzes the hydrolysis of cholesterol esters, esters of fat-soluble vitamins, and phospholipids, as well as triglycerides. Fats are relatively insoluble, which limits their ability to cross the unstirred layer and reach the surface of the mucosal cells. However, they are finely emulsified in the small intestine by the detergent action of bile salts, lecithin, and monoglycerides. Inside the cells, the lipids are rapidly esterified, maintaining a favorable concentration gradient from the lumen into the cells (Figure 276). There are also carriers that export certain lipids back into the lumen, thereby limiting their oral availability. Fatty acids containing less than 10 to 12 carbon atoms are water-soluble enough that they pass through the enterocyte unmodified and are actively transported into the portal blood. The fatty acids containing more than 10 to 12 carbon atoms are too insoluble for this. The triglycerides and cholesterol esters are then coated with a layer of protein, cholesterol, and phospholipid to form chylomicrons. These leave the cell and enter the lymphatics, because they are too large to pass through the junctions between capillary endothelial cells (Figure 276). In mucosal cells, most of the triglyceride is formed by the acylation of the absorbed 2-monoglycerides, primarily in the smooth endoplasmic reticulum. However, some of the triglyceride is formed from glycerophosphate, which in turn is a product of glucose catabolism. Most vitamins are absorbed in the upper small intestine, but vitamin B12 is absorbed in the ileum. This vitamin binds to intrinsic factor, a protein secreted by the stomach, and the complex is absorbed across the ileal mucosa (see Chapter 26). Vitamin B12 absorption and folate absorption are Na+-independent, but all seven of the remaining water-soluble vitamins-thiamin, riboflavin, niacin, pyridoxine, pantothenate, biotin, and ascorbic acid-are absorbed by carriers that are Na+ cotransporters. Apoproteins synthesized in the rough endoplasmic reticulum are coated around lipid cores, and the resulting chylomicrons are secreted from the basolateral pole of epithelial cells by exocytosis. The acylation of glycerophosphate and the formation of lipoproteins occur in the rough endoplasmic reticulum. Carbohydrate moieties are added to the proteins in the Golgi apparatus, and the finished chylomicrons are extruded by exocytosis from the basal or lateral aspects of the cell. Absorption of long-chain fatty acids is greatest in the upper parts of the small intestine, but appreciable amounts are also absorbed in the ileum. The processes involved in fat absorption are not fully mature at birth, and infants fail to absorb 1015% of ingested fat. Thus, they are more susceptible to the ill effects of disease processes that reduce fat absorption. The absorptive process and its relation to 1,25-dihydroxycholecalciferol are discussed in Chapter 23. Through this vitamin D derivative, Ca2+ absorption is adjusted to body needs; absorption is increased in the presence of Ca2+ deficiency and decreased in the presence of Ca2+ excess. It is inhibited by phosphates and oxalates because these anions form insoluble salts with Ca2+ in the intestine. They are formed by the action of colonic bacteria on complex carbohydrates, resistant starches, and other components of the dietary fiber, that is, the material that escapes digestion in the upper gastrointestinal tract and enters the colon. In addition, they exert a trophic effect on the colonic epithelial cells, combat inflammation, and are absorbed in part by exchange for H+, helping to maintain acidbase equilibrium. The losses are generally unregulated, and total body stores of iron are regulated by changes in the rate at which it is absorbed from the intestine. Women have a variable, larger loss averaging about twice this value because of the additional iron lost during menstruation. The average daily iron intake in the United States and Europe is about 20 mg, but the amount absorbed is equal only to the losses. Various dietary factors affect the availability of iron for absorption; for example, the phytic acid found in cereals reacts with iron to form insoluble compounds in the intestine, as do phosphates and oxalates. Most of the iron in the diet is in the ferric (Fe3+) form, whereas it is the ferrous (Fe2+) form that is absorbed. Gastric secretions dissolve the iron and permit it to form soluble complexes with ascorbic acid and other substances that aid its reduction to the Fe2+ form. The importance of this function in humans is indicated by the fact that iron deficiency anemia is a troublesome and relatively frequent complication of partial gastrectomy. Some is stored in ferritin, and the remainder is transported out of the enterocytes by a basolateral transporter named ferroportin 1. In the plasma, Fe2+ is converted to Fe3+ and bound to the iron transport protein transferrin. Normally, transferrin is about 35% saturated with iron, and the normal plasma iron level is about 130 g/dL (23 mol/ L) in men and 110 g/dL (19 mol/L) in women. Heme (see Chapter 32) binds to an apical transport protein in enterocytes and is carried into the cytoplasm. Seventy percent of the iron in the body is in hemoglobin, 3% in myoglobin, and the rest in ferritin, which is present not only in enterocytes, but also in many other cells. Ferritin is readily visible under the electron microscope and has been used as a tracer in studies of phagocytosis and related phenomena. Ferritin molecules in lysosomal membranes may aggregate in deposits that contain as much as 50% iron. Intestinal absorption of iron is regulated by three factors: recent dietary intake of iron, the state of the iron stores in the body, and the state of erythropoiesis in the bone marrow. The normal operation of the factors that maintain iron balance is essential for health (Clinical Box 272).
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It turns out to the treatment 2014 order arava now be immensely complex because when pain is prolonged and tissue is damaged medications similar to xanax order arava 20mg with mastercard, central nociceptor pathways are sensitized and reorganized medicine vs nursing buy cheapest arava and arava. One system comprises thinly myelinated A fibers (25 m in diameter) which conduct at rates of 1230 m/s. Cold receptors are on dendritic endings of A fibers and C fibers, whereas warmth (heat) receptors are on C fibers. Thermal nociceptors are activated by skin temperatures above 45 °C or by severe cold. Chemically sensitive nociceptors respond to various agents like bradykinin, histamine, high acidity, and environmental irritants. The threshold for activation of warmth receptors is 30 °C, and they increase their firing rate up to 46 °C. Cold receptors are inactive at temperatures of 40 °C, but then steadily increase their firing rate as skin temperature falls to about 24 °C. As skin temperature further decreases, the firing rate of cold receptors decreases until the temperature reaches 10 °C. Below that temperature, they are inactive and the cold becomes an effective local anesthetic. Because the sense organs are located subepithelially, it is the temperature of the subcutaneous tissues that determines the responses. Cool metal objects feel colder than wooden objects of the same temperature because the metal conducts heat away from the skin more rapidly, cooling the subcutaneous tissues to a greater degree. A major advance in this field has been the cloning of three thermoreceptors and nociceptors. There may be many types of receptors on single peripheral C fiber endings, so single fibers can respond to many different noxious stimuli. Aside from the fact that activation of the cool receptor causes an influx of Ca2+, little is known about the ionic basis of the initial depolarization they produce. In the cutaneous receptors in general, depolarization could be due to inhibition of K+ channels, activation of Na+ channels, or inhibition of the Na+K+ pump, but the distinction between these possibilities has not been made. Especially in areas where many naked endings of unmyelinated nerve fibers occur, itch spots can be identified on the skin by careful mapping. In addition, itch-specific fibers have been demonstrated in the ventrolateral spinothalamic tract. Relatively mild stimulation, especially if produced by something that moves across the skin, produces itch and tickle. Scratching relieves itching because it activates large, fast-conducting afferents that gate transmission in the dorsal horn in a manner analogous to the inhibition of pain by stimulation of similar afferents. It is interesting that a tickling sensation is usually regarded as pleasurable, whereas itching is annoying and pain is unpleasant. Itching can be produced not only by repeated local mechanical stimulation of the skin but also by a variety of chemical agents. Histamine produces intense itching, and injuries cause its liberation in the skin. However, in most instances of itching, endogenous histamine does not appear to be the responsible agent; doses of histamine that are too small to produce itching still produce redness and swelling on injection into the skin, and severe itching frequently occurs without any visible change in the skin. A painful stimulus causes a "bright," sharp, localized sensation (fast pain) followed by a dull, intense, diffuse, and unpleasant feeling (slow pain). Evidence suggests that fast pain is due to activity in the A pain fibers, whereas slow pain is due to activity in the C pain fibers. Pain is frequently classified as physiologic or acute pain and pathologic or chronic pain, which includes inflammatory pain and neuropathic pain. Acute pain can be considered as "good pain" as it serves an important protective mechanism. Chronic pain can result from nerve injury (neuropathic pain) including diabetic neuropathy, toxin-induced nerve damage, and ischemia. Hyperalgesia is an exaggerated response to a noxious stimulus, whereas allodynia is a sensation of pain in response to an innocuous stimulus. An example of the latter is the painful sensation from a warm shower when the skin is damaged by sunburn. For example, in causalgia, spontaneous burning pain occurs long after seemingly trivial injuries. In this condition, the skin in the affected area is thin and shiny, and there is increased hair growth. Research in animals indicates that nerve injury leads to sprouting and eventual overgrowth of noradrenergic sympathetic nerve fibers into the dorsal root ganglia of the sensory nerves from the injured area. Thus, it appears that the periphery has been short-circuited and that the relevant altered fibers are being stimulated by norepinephrine at the dorsal root ganglion level. Alpha-adrenergic blockade produces relief of causalgia-type pain in humans, though for unknown reasons 1-adrenergic blockers are more effective than 2-adrenergic blocking agents. Treatment of painful sensory neuropathy is a major challenge and current therapies are often inadequate. Some released substances act by releasing another one (eg, bradykinin activates both A and C fibers and increases synthesis and release of prostaglandins). Prostaglandin E2 (a cyclooxygenase metabolite of arachidonic acid) is released from damaged cells and produces hyperalgesia. This is probably due to a relative deficiency of A nerve fibers in deep structures, so there is little rapid, bright pain. In addition, deep pain and visceral pain are poorly localized, nauseating, and frequently associated with sweating and changes in blood pressure. Pain can be elicited experimentally from the periosteum and ligaments by injecting hypertonic saline into them. The pain produced in this fashion initiates reflex contraction of nearby skeletal muscles. This reflex contraction is similar to the muscle spasm associated with injuries to bones, tendons, and joints. The steadily contracting muscles become ischemic, and ischemia stimulates the pain receptors in the muscles (see Clinical Box 103). Hyperalgesia and allodynia signify increased sensitivity of nociceptive afferent fibers. Figure 101 shows how chemicals released at the site of injury can further activate nociceptors leading to inflammatory pain. Injured cells release chemicals such as K+ that depolarize nerve terminals, making nociceptors more responsive. Injured cells also release bradykinin and Substance P, which can further sensitize nociceptive terminals. Substance P acts on mast cells to cause degranulation and release histamine, which activates nociceptors. The receptors in the walls of the hollow viscera are especially sensitive to distention of these organs.