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Tryptase levels can be used in forensic investigations to confrm death from anaphylaxis Allergy blood testing: a practical guide for clinicians buy 1mg anastrozole visa women's health clinic lubbock. Blood tests are available that measure levels of specifc immu- noglobulin E (IgE) against venoms 1mg anastrozole with visa women's health clinic lethbridge. Causes of ant sting anaphylaxis in Australia: the Austra- lian Ant Venom Allergy Study order anastrozole canada women's health center delaware. Serum IgE testing against ant venom panels was used to deter- mine the Australian native ant species associated with ant sting anaphylaxis cheap anastrozole master card women's health center at centrastate. This chapter presents strategies for the prevention and manage- Diagnostic venom-specifc IgE testing is now feasible and being used ment of bites and stings. Detection of West Nile virus genome and specifc antibod- Bite reactions ies in Iranian encephalitis patients. The authors studied a total of 632 patients with fever and loss A veterinarian should be consulted about fea infestation in pets. If prevention fails, second line treatments aim to improve pru- A history of insect bite, blood transfusion and transplantation are ritus. The two assays and topical anesthetics, such as pramoxine and lidocaine, can be are complementary. For persistent bite reactions, topical or intralesional cor- ticosteroids may be helpful. Individuals who experience anaphylaxis in response to stings Biting midges of the genus Culicoides cause insect bite hyper- should be referred to an allergist for desensitization. As they are very small, sitization is possible for those with life-threatening allergy. The assays require improvement, but are promising for identifcation Vector-borne disease of small species of insects. For early Lyme Usefulness of post mortem determination of serum trypt- disease, evidence suggests that a 10-day course is as effective as ase, histamine and diamine oxidase in the diagnosis of fatal longer courses of antibiotic. Atovaquone–proguanil Signifcantly higher histamine levels were present in blood has been effective in refractory cases in immunocompromised samples taken more than 24 hours post mortem, and the timing patients. Scorpion stings The combination of treated nets and climatic events led to the Antivenin for stings in Arizona B collapse of malaria vector populations in a malaria-endemic area Prazosin for Indian red scorpion stings A with a low-density human population. Arthropod-borne infections Impregnated netting has been shown to reduce disease transmission Lyme borreliosis and may help eliminate populations of disease vectors. A study of long-lasting insecticide (deltamethrin)-treated nets The number of tick bites received by individuals wearing confrmed that 37% of Anopheles gambiae mosquitoes had become permethrin-treated summer clothing (T-shirt, shorts, socks, and resistant to deltamethrin by 2010, and the prevalence of sneakers) was decreased by almost fvefold. Among those who a common resistance mutation increased from 8% to 48% still had attachments, signifcantly fewer (22. Increasing pyrethroid resistance contributed to a rebound of malaria This study demonstrates the value of permethrin-treated summer morbidity. This study supports the use of synergistic combinations of clothing to reduce tick attachments and tick-borne pathogen insecticides rather than single agents. Scorpion envenomations in young children in central Pilot study assessing the effectiveness of long-lasting Arizona. J Toxicol Clin Toxicol 2003; permethrin-impregnated clothing for the prevention of tick 41: 937–40. Vector Borne Zoonotic Dis 2011; The mean time of abatement of symptoms following antivenin 11: 869–75. There was one acute rash to anti- A non-randomized open label feld trial among outdoor venin and 49 cases (57%) of serum sickness. Pain ment of severe Mesobuthus tamulus (Indian red scorpion) reduction was the dominant effect. Objective data are needed to demon- Twenty (80%) of those in the antivenin group had acute strate comparative effectiveness, as ice remains very inexpensive by pulmonary edema versus two (7. Four patients in the frst group and none in the second group Field evaluation of commercial repellents against the died. Incorvaia C, Frati F, Dell’Albani I, Robino A, diethyl-m-toluamide/N,N-diethyl-3-methyl-benzamide, also Cattaneo E, Mauro M, et al. The second contained 3% soybean oil, 6% A systematic review of the literature on venom immunotherapy geranium oil, and 8% castor oil, and the third contained 7. This study provides further evidence that botanicals can be effective While venom immunotherapy can improve quality of life, this study as repellents. The dogma has been that such treatment is largely ineffective Repellents where habitats are so extensive that they cannot be covered on Botanicals B–C foot. Unlike other pyrethroids, may Teatment of bite reactions not require heating and is suitable for use in fan vaporizers as well as in paper and resin emanators. J Am Mosq Control Assoc an alternative to reduce swelling, pain, and pruritus: an 2012; 28: 15–19. Clin Cosmet Investig suaveolens, showed promise against mosquitos under both labora- Dermatol 2011; 4: 191–6. In the laboratory, the repellency was A medical device of class 2A (non-invasive device) to reduce assessed against Anopheles gambiae, based on a 15 minute landing swelling, pruritus, and pain after insect bites/stings via direct heat and biting on treated forearms of volunteers. The products were tested on human volunteers in t results from a pilot effcacy study. This pilot effcacy study showed 83% fewer Anopheles Lutzomyia migonei (Diptera: Psychodidae). The plants included Hyptis suaveo- may play a role, especially in areas with limited resources. The most frequently recorded species was Lippia 95% protection against bites of L. Typically, it was the leaves that were used, tions of indian red scorpion (Mesobuthus tamulus concanesis and in a dry state. In addition to the data noted above, nine plant species were docu- Pulmonary edema resolved in all 15 patients treated with cap- mented for the frst time as mosquito repellents. Of the nine patients with Effcacy of Advanced Odomos repellent cream (N, cardiogenic shock, six received captopril and one of these patients N-diethyl-benzamide) against mosquito vectors. Bioassays were used as the basis for did not respond to pressors were not treated with captopril. In addition, long-term treat- ment with ketoconazole is associated with adverse effects. The 28 Blastomycosis new generation azoles, voriconazole and posaconazole, have demonstrated activity against B. The experience to date has been largely with the use of amphotericin B deoxycholate. After an initial response with amphotericin B, step-down therapy to an azole is common practice. It is acquired by inhalation of the conidia which are trans- direct examination of tissue or the isolation of Blastomyces in formed into the yeast form in the lungs. Cases have also been reported in Latin tissue biopsy specimens, cerebrospinal fuid or urine produces a America, Africa, the Middle East and India. Consequently, the white mould at 25°C on Sabouraud’s agar, and a brown wrinkled term ‘North American blastomycosis’ is now obsolete.
The hemi 3 syn- drome: hemihypertrophy order anastrozole line women's health zymbiotix, hemihypaesthesia buy anastrozole in india premier women's health boca raton, hemiarefexia and sco- liosis cheap anastrozole line women's health center doctors west. Background In 1983 the German pediatrician Hans-Rudolf Wiedemann and his coauthors discount anastrozole 1 mg free shipping menopause young living,  unaware of Cohen and Hayden’s earlier paper, [2,3] described a new syndrome in four unrelated boys with the combination of partial gigantism of the hands and/or feet, nevi, hemihypertrophy, subcutane- ous tumors, and macrocephaly. They proposed the term Pro- teus syndrome and named it after the Greek sea-god Proteus “the polymorphous”, who is gifted with the ability to change his form at will. The condition described by Temtamy and Rogers  in 1976 may fall into the same category. It is also possible that the horribly disfgured, articulate English gentleman Joseph Merrick, known by most as the Elephant Man, had the Proteus syndrome, not neurofbroma- tosis. This involvement are more consistent with the Proteus syndrome, not Von story has been widely repeated and the subject of two books, Recklinghausen disease (neurofbromatosis), the diagnosis that had been perpetuated for a century. For signifcant overgrowth of the entire right side of the cranium and facial years he was displayed as a “human curiosity” and since his bones, well demonstrated with the soft tissue removed. Skeletal masses death his articulated skeleton has been permanently displayed are exostoses. At the time there Presentation Most newborns may be normal at birth but a was great speculation regarding the proper diagnosis as the few may have manifestations at birth. The clinical morphol- differential contained every diagnosis outlined above in the ogy of this condition is highly variable with a complex mul- macrodactyly section. This syndrome is a true mosaic of many phenotypes Cohen to clarify the proper diagnosis in this man for several and no two limbs are alike. Exami- Patients have tumor formation susceptibility and may have nation of Merrick’s spine revealed changes more consistent fatal thromboembolism from vascular malformations. Mobil- and long metacarpals are within the feld of overgrowth and the ring and ity is decreased and fexion contractures have developed in both digits. Over- tion is rapidly progressive and disfguring in contrast to other Upper extremity Disproportionate gigantism of the upper forms of overgrowth. Asymmetric over- and/or limbs or may be more diffuse involving the entire growth is seen in the digits and thumb (. The overgrowth cartilaginous masses originating within or adjacent to the vo- deformity typically accentuates with growth and is character- lar plates of the interphalangeal joints. Pelvic and lower extremity distortion will Dermatologists also call this a connective tissue nevus. The hypertrophied, cerebriform including the mandible and may result in deafness or blind- skin on the palmar surfaces is antithetical to function. Hyperplasia of osteoid tissue with variable calcifca- The affected digits are long, angular and contain hard, im- tion produces abnormal bony ridges and soft tissue calcif- mobile masses that impinge upon joint mobility. Facial distortion is progressive and characteristic fea- distortion does not have any characteristic pattern as one or tures include a long face, down-slanting palpebral fssures, more limbs may be involved. Soft tissue calcifcation is not mandibular prognathism, open mouth, low nasal bridge, and seen early in childhood but is very common as these children anteverted nasal ala. Once the facial growth asymmetries progress through the adolescent growth spurt (. Fortunately, most joints for three reasons: obstructing soft tissue, cartilaginous of these children and adults do not have signifcant cutane- masses, and distortion of the interphalangeal joints, which ous infltration. Secondary degenerative joint changes are not as fulminant Systemic Visceral malformations and malignancies may as those seen with lipomatous types of macrodactyly. These develop later in adulthood including ovarian tumors and me- radiographic changes can usually be distinguished from other ningiomas. The skeletal Specifc diagnostic criteria have been established as a overgrowth occurs in all three dimensions, length, width and result of a workshop at the National Institutes of Health in circumference and like the facial features is rapidly progres- March 1998 . Involved carpal bones will enlarge disproportionately cifc criteria, based upon category signs A, B, or C must be and distort the remaining uninvolved structures. A single category sign in A is suffcient for a Proteus carpal bones do not appear. Either two signs in category B or three signs in the involved rays of the hand are invariably within the zone of category C are suffcient. The growth plates of these tubular bones may demon- References strate an asymmetric involvement. Carpal coalitions do not occur unless they fuse spontaneously following infamma- 1. The Proteus syn- drome: partial gigantism of the hands and/or feet, nevi, hemihyper- tory episodes. Arms and forearms have hypoplastic soft tissue trophy, subcutaneous tumors, macrocephaly or other skull anomalies musculature and limitation of motion is common. Macrodactyly, hemihypertrophy, and con- nective tissue nevi: Report of a new syndrome and review of the infltration is also seen with and without dorsal skin infl- literature. Note ulceration, infection, and a fetid odor make these children very symp- the asymmetry of the affected digits. This girl involved but only an isolated segment of the right long and left index subsequently developed ovarian cystadenomas and a massive hypertro- are overgrown. The hard fbrotic mass on the dorsal right index fnger phy of her right breast is in the subcutaneous tissue plane. Proteus syndrome: di- agnostic criteria, differential diagnosis, and patient evaluation. Background In 1938 Lichtenstein introduced the term f- brous dysplasia for a developmental anomaly characterized by the replacement of the medullary canal by fbrous tissue Fig. This could in- 1969) volve a single bone or multiple bones and later would be recognized as monostotic or polyostotic fbrous dysplasia . Isolated lesions in the middle, distal, and occasionally the proximal phalanges Etiology Early embryonal postzygotic somatic activating have been reported. The radiographs show intrinsic expan- Presentation This is a rare condition in the upper extremity. Destructive, erosive changes and presents usually with two or three components of the do not predominate. Affected bones can become quite large and patients present with pain, pathologic fractures, and Lower extremity Long bones may be involved and the fe- spinal, facial and lower limb deformity. The upper limbs are mur may demonstrate a shepherd’s crook deformity with a not frequently involved. Radiographs show a typical ground glass appearance and a Spine Scoliosis and Kyphoscoliosis. Many endocrine abnormalities become evident deafness may result from expansion of these structures and later in childhood, especially in boys who have precocious impingement of one or more cranial nerves and orbital struc- puberty. Although this is an uncommon cause of enlargement of the hand, it is commonly part of the differential diagnosis of macrodactyly involving the upper limb. The cortices are thin and there is displayed premature sexual development and asymmetry of the face.
Mild deviations do not do description of the progression of infection from susceptibility to much harm order anastrozole overnight delivery women's health center bethlehem pa. If This fgure makes it seem as though a large percentage of exposed many variables are binary order anastrozole 1 mg line women's health center in austin, then the foregoing procedure cases are infected and a substantial portion manifest the disease order 1 mg anastrozole otc menstrual gas pains, but is questionable quality 1mg anastrozole women's health center northfield mn. In that case, use a logistic discriminant actually, these proportions are small in practice for most diseases. Susceptibility is a property matrices are really very different, the linear discriminant of the host. Infectiousness is the property of the agent that causes function is not adequate in separating the groups. Sex determination by dis- sons who get the actual disease after the exposure can be called criminant analysis of patella measurements. Hodder the severe form of disease requiring hospitalization and have a Arnold, 2001. A Pearsonian correlation coeffcient is obtained when these variances and the covariances are divided by the multiplication of the respective standard deviations. In that case, all the diagonal elements of this matrix are equal to 1, and the off- diagonal elements are the Pearsonian correlation coeffcients. The terms pathogenic and virulent are borrowed from the feld distal measures, see proximal and distal of infectious diseases but can be used for chronic diseases as well, as long as the meaning is explained. Division of cases into such a measures of health and disease spectrum can help in choosing treatment strategies and in prognostic assessments. If an infected person is able to infecThat least one person on average during the entire period of infectivity, then the infection will be sustained or increase. This is called the reproductive num- distributions (statistical) ber of the infection. In countries where hepatitis B infection is on Statistical distribution of a variable describes which values are more the rise, this rate is more than 1. If the reproductive rate is less than 1, common than others, which values are unlikely, which values do not expect that the infection will die down or stabilize at a low level. For example, see the distribution of hemoglobin (Hb) values DisMod, see epidemiologically consistent estimates in women in Figure D. Values like 7–8 and 14–15 g/dL dispersion, see variation (measures of) are least common; perhaps not even 1 in 50 women has such low or high values. It also shows that values below 12–13 g/dL are more common than dispersion matrix values above, etc. The statistical distribution characterizes all the features of the In a multivariate setup, the variables have not just variances but data and helps us to determine what type of analysis should be also covariances. If these variables are (x1, x2, …, xK), the covari- done and which statistical methods should be used to derive valid ance will be between x1 and x2, between x1 and x3, etc. In short, the distribution is the backbone of the statisti- matrix (also called the variance–covariance matrix or just covari- cal methods. Mathematical formulation of these distributions helps ance matrix) is the arrangement of these variances and covariances in accurately working out the theoretical mean, variance, and such in a square format such that the element in the ith row and jth col- other parameters, as also the probabilities of any value bigger than or umn is the covariance between xi and xj. Such probabilities are required primarily that the “covariance” between xi and xi, σii, is the same as the vari- ance of xi. Elements in the matrix give an indication as to how much dispersed values of each variable are and how much these are dependent on one another. Distributions of the discrete variables are called discrete Hypertens 1999 Feb;12(2 Pt 2):35S–42S. Diurnal mood variation in depression: A signal of dis- of hypergeometric, negative binomial, and uniform distributions. Similarly, major continuous variables (distribution of) are between free thyroxine and thyrotropin and its clinical relevance. Besides whether the distribution is discrete or continuous, other doctor–population ratio, see health considerations while looking at any distribution for a statistical method are skewness and sometimes kurtosis. These features are measured infrastructure (indicators of) as deviations, if any, from the Gaussian (normal) distribution—a central distribution for statistical theory and practices. When there donut diagram are signifcant deviations, the distribution is generically termed non-Gaussian. When the distribution is highly skewed and sample Make a hole in a pie diagram and get a donut. Both have the same size is not large, generally, nonparametric methods are preferred functionality and the same requirement. This shows that females are nearly one-half of These would not be applicable if the distribution were highly skewed males, as depicted by the size of the donuts in this fgure. For conditions that allow use of a the large percentage of those aged 35–44 years in females is shown Gaussian distribution, see the topic Gaussian conditions. The preceding discussion is restricted to what are called univari- The Slide Team  gives an excellent description of how donut ate distributions, since only one variable is being considered, but diagrams can help in effective PowerPoint presentations. These generally occur due to the dra- It may not be exactly true for a treatment regimen, but most toxic matic effect of the day-and-night cycle on our physiological pro- substances (such as insecticides) exhibit the property that higher cesses, as evidenced by the alternation of duration of activity and dose results in higher response—in the case of insecticides, the sleep. The same property is exhibited by most anes- between circadian rhythm and diurnal variation, but practically, thetic agents, where the response is the duration or effectiveness in there is no difference. The clinical onset of both myocardial infarction and stroke occurs more frequently in the early morning than at other times of day . Statistically, diurnal variations contribute to the uncertainties in interpretation of values, as illustrated by Goede et al. Indeed, many studies seem to ignore or forget about such variation, possibly leading to less valid conclusions. For measurements that show diurnal variation, the assessment in a research setup should be done at the same time of the day in all the subjects, and this time should be clearly mentioned in the article. This could be positive (response increases with higher dose), nega- tive (response decreases with higher dose), or none at all (response remains the same with changed dose). The relationship could be lin- ear (each unit of additional dose brings about the same additional response) or multiplicative (each unit of additional dose has, say, twice as much effect as the previous dose), or can have any other pattern. For example, log(dose) is used in place of dose, and square root of response is used in place of response. Each observation is represented by a dot against the called dose and response metameters, respectively. Thus, there are as many is examined by the methods used in bioassays, such as parallel-line dots as the number of subjects. A dose–response relationship occurs in many other medical set- When a dot is representing more than one subject, this should be ups. In this case, you can have a proportionate doThat the exposures and the effect of noise or air pollution. For a dose–response relationship between maternal parity and risk of such data, a dot plot is an alternative to a histogram, and the same congenital heart defects in offspring. For example, you can talk about variability ples are available in the medical literature. But the dot plot suits well when the “values” on the cates a cause-and-effect kind of relationship, there are a good num- x-axis are qualitative. These can be values such as site of injury, ber of criteria to consider, as enumerated by Indrayan .
Tis by zone 3 (Pa > Pv > Pa) purchase anastrozole with visa best women's health tips, where both Pa and Pv are response seems to be due to either the direct efect of higher than Pa buy 1mg anastrozole fast delivery women's health center encinitas, resulting in blood fow independent hypoxia on the pulmonary vasculature or increased of the alveolar pressure purchase 1mg anastrozole with amex obama women's health issues. Zone 4 anastrozole 1 mg online pregnancy xx massage, the most dependent production of leukotrienes relative to vasodilatory part of the lung, is where atelectasis and/or intersti- prostaglandins. Inhibition of nitric oxide production tial pulmonary edema occur, resulting in blood fow may also play a role. Hypoxic pulmonary vasocon- that is dependent on the diferential between Pa and striction is an important physiological mechanism pulmonary interstitial pressure. V/Q for individual lung units (each alveolus and increase in alveolar ventilation. An appreciable com- its capillary) can range from 0 (no ventilation) to pensatory increase in O2 uptake cannot take place infnity (no perfusion); the former is referred to as in remaining areas where V/Q is normal, because intrapulmonary shunt, whereas the latter constitutes • pulmonary end-capillary blood is usually already alveolar dead space. Because perfusion increases at a greater rate than ventilation, nonde- • pendent (apical) areas tend to have higher V/Q ratios 3. Absolute shunt refers to ana- with the law for the conservation of mass for O • 2 tomic shunts and lung units where V/Q is zero. A across the pulmonary bed: • relative shunt is an area of the lung with a low V/Q ratio. Clinically, hypoxemia from a relative shunt Qt × Cao2= (Qs × Cvo2) + (Qc´× C c´o 2) can usually be partially corrected by increasing the where inspired O2 concentration; hypoxemia caused by an absolute shunt cannot. Qs = blood fow through the physiologic shunt compartment Venous Admixture Qt = total cardiac output Qc´& = blood fow across normally ventilated Venous admixture refers to a concept rather than an actual physiological entity. Venous admixture is pulmonary capillaries the amount of mixed venous blood that would have Qt& = Qc´& + Qs& to be mixed with pulmonary end-capillary blood to Cc´o2 = oxygen content of ideal pulmonary account for the diference in O2 tension between arte- end-capillary blood rial and pulmonary end-capillary blood. Normal • Qs/Qt is primarily due to communication between • C c´o 2 − Cao2 Qs/Qt = deep bronchial veins and pulmonary veins, the the- C c´o − Cvo 2 2 besian circulation in the heart, and areas of low V/Q in the lungs (Figure 23–18). The venous admixture The formula for calculating the O2 content of in normal individuals (physiological shunt) is typi- blood is given below. Qs/Qt can be calculated clinically by obtaining mixed venous and arterial blood gas measurements; 4. The alveolar gas equation is used to derive pulmo- on Gas Exchange nary end-capillary O2 tension. Pulmonary capillary Abnormalities in gas exchange during anesthesia are blood is usually assumed to be 100% saturated for common. General admixture and preventing hypoxemia during gen- 10 anesthesia commonly increases venous admix- eral anesthesia, as long as cardiac output is main- ture to 5% to 10%, probably as a result of atelectasis tained Prolonged administration of high inspired and airway collapse in dependent areas of the lung. O2 concentrations may be associated with atelecta- Inhalation agents, including nitrous oxide, also can sis formation and increases in absolute shunt. Elderly ratio ventilated at an O - inspired concentration • 2 patients seem to have the largest increases in Qs/Qt. Perfusion results in O being trans- 2 Inspired O2 tensions of 30% to 40% usually prevent ported out of the alveoli at a rate faster than it hypoxemia, suggesting anesthesia increases relative enters the alveoli, leading to an emptying of the shunt. Note that large barometric pressure is 760 mm Hg (sea level), the 11 increases in Paco2 ( >75 mm Hg) readily pro- partial pressure of O (P o 2 2) in air is normally 159. Pio2 = Pb × Fio2 Pulmonary End-Capillary where P b = barometric pressure and Fio2 = the frac- Oxygen Tension tion of inspired O. Enhanced O 2 2 binding to hemoglobin at saturations above 80% Alveolar Oxygen Tension also augments O difusion (see below). Capillary 2 With every breath, the inspired gas mixture is transit time can be estimated by dividing pulmonary humidifed at 37°C in the upper airway. The inspired capillary blood volume by cardiac output (pulmo- tension of O2 ( P i o 2) is therefore reduced by the nary blood fow); thus, normal capillary transit time added water vapor. Maximum Pc′ o 2 is dent only upon temperature and is 47 mm Hg at usually attained afer only 0. Terefore, pulmo- The general equation is nary difusing capacity refects not only the capacity and permeability of the alveolar–capillary mem- Pio2 = (Pb − Ph2o) × Fio2 brane, but also pulmonary blood fow. Moreover, where P h2 o = the vapor pressure of water at body O2 uptake is normally limited by pulmonary blood temperature. The fnal alveolar and in patients with extensive destruction of the O2 tension (P ao2) is therefore dependent on all of alveolar–capillary membrane. Terefore, Decreased hemoglobin concentration 1 Carbon monoxide uptake V/Q , ventilation/perfusion. Dlco = Paco depends on cardiac output, O2 consumption, and Reductions in Dlco imply an impediment in hemoglobin concentration. The efect of each variable on Pao2 (and capillary membrane, or very short capillary transit consequently the A–a gradient) can be determined times. Abnormalities are accentuated by increases in only when the other variables are held constant. O2 consumption and cardiac output, such as occurs Figure 23–19 shows the efect of diferent degrees of during exercise. It should also be noted that 13 the greater the shunt, the less likely the possi- Arterial Oxygen Tension bility that an increase in Fio2 will prevent hypoxemia. Pa o2 cannot be calculated like Pao2 but must be Moreover, isoshunt lines seem to be most useful for measured at room air. Lower O 2 2 partial pressure gradient (A–a gradient) is normally concentrations require modifcation of isoshunt lines less than 15 mm Hg, but progressively increases to account for the efect of V/Q scatter. Arterial O2 tension The efect of cardiac output on the A–a gradi- can be approximated by the following formula (in ent (Figure 23–20) is due not only to its second- mm Hg): ary efects on mixed venous O tension but also to 2 Age a direct relationship between cardiac output and Pao2 = 120 − 3 intrapulmonary shunting. As can be seen, a low car- diac output tends to accentuate the efect of shunt The range is 60–100 mm Hg (8–13 kPa). Carbon Dioxide Carbon dioxide is a by-product of aerobic metabo- lism in mitochondria. Note that there is little 2 2 activity (eg, skin), but higher in blood from those beneﬁt in increasing inspired oxygen concentration in patients with very large shunts. Each gram of hemoglobin can theo- tration of any gas in solution is proportional to its retically carry up to 1. The mathematical expression is as follows: Hemoglobin Dissociation Curve Gas concentration = α × Partial pressure Each hemoglobin molecule binds up to four O2 where α = the gas solubility coefcient for a given molecules. Even with a Hemoglobin saturation is the amount of O bound 2 Pa o 2 of 100 mm Hg, the maximum amount of O2 as a percentage of its total O -binding capacity. The change in 2 molecular conformation induced by the binding of Hemoglobin the frst three molecules greatly accelerates bind- Hemoglobin is a complex molecule consisting ing of the fourth O molecule. Heme is responsible for the accelerated binding between 25% an iron–porphyrin compound that is an essen- and 100% saturation. At about 90% saturation, the tial part of the O2-binding sites; only the divalent decrease in available O receptors fattens the curve 2 form (+2 charge) of iron can bind O. Factors Inﬂuencing the venous blood than arterial blood (Figure 23–23); the net result is facilitation of O2 release to tissue Hemoglobin Dissociation Curve with little impairment in O2 uptake (unless severe Clinically important factors altering O2 binding hypoxia is present). Carbon monoxide is particularly potent, having 200–300 times the afnity of O2 for Oxygen Transport hemoglobin, combining with it to form carboxyhe- O transport is dependent on both respiratory and 2 • moglobin.