Acidosis; first we evaluate the primary disorder, and the definitions of the primary disorder. If you think about acid-base balance in a logical stepwise fashion, you may be able to remember it and figure it out. If you don’t do it in a logical stepwise fashion you are almost for sure not going to be able to do it, and even if you do think about it in a logical stepwise fashion, a lot of people have problems with it – like me. So it’s got to be logical and stepwise. So number one, we think of the primary disorder. What is the primary disorder? If there is metabolic acidosis, the pH is low compared to 7.4. If the primary cause is loss of bicarbonate, the lab finding; a low CO2. I make a big differential here between CO2 and of course PCO2. Because PCO2 is the respiratory component, the carbonic acid. If there is a respiratory acidosis – you have again, a low pH – you have increased carbonic acid and that’s an increased PCO2. So contrast these two. If it’s alkalosis the pH is high and metabolic alkalosis is caused by increased bicarbonate or low chlorides, and an increased CO2 is found in your electrolytes. Respiratory, again an increased pH, a low bicarbonate, a low PCO2. This is important to review. This seems simple. You guys have gone over it again and again, but this is important to review and be sure you’ve got cold.
Canadian pharmacy nexium
The compensations are likewise important. Remember, you can never overcompensate so you determine the primary changes first. Metabolic acidosis, low CO2. What is the compensation? The compensation is in the other system; increased ventilation, and the result is decreased PCO2. But the primary is an acid pH in the blood and a low CO2. Respiratory acidosis, the primary change, high PCO2. Retained PCO2. The compensation is renal bicarbonate absorption and a high CO2. If you are acidotic and you see these two things, you are going to know that first, this is what would give you the high … the respiratory acidosis. Below the 7.2 type of blood pH. Remember please, that you cannot make a distinction of whether a patient is acidotic or alkalotic unless you have either a venous blood gas or an arterial blood gas that shows a pH. These numbers in and of themselves cannot show you whether the patient is acidotic or alkalotic. Very important to remember.
Cocaine
Drugs and Chemicals Associated with Birth Defects
Cocaine (street names “coke;’ “snow;’ “lady;’ and “gold dust”) use is a major public health concern. Use of cocaine in the 1970s was primarily limited to the intranasal route. In the 1980s, a decrease in the street cost and wider availability of cocaine resulted in an increasing prevalence of intravenous and smoked (”free-base” or “crack”) routes of use. Consequently, the prevalence of cocaine-associated medical complications has increased. Cocaine is commonly used intranasally (”snorting”), by injection, and by smoking the free alkaloid form (crack). Crack (named after the cracking or popping sound that is made when the crystals are ignited in a pipe while smoking the drug) is a highly purified form of free alkaloid cocaine. In a survey of a number of urban hospitals nationwide, positive urine toxicology for cocaine metabolites was detected among 10-48% of pregnant women. The crack form of cocaine is believed to be more addictive than other forms. Administered systemically, cocaine blocks the presynaptic reuptake of neurotransmitters (norepinephrine and dopamine), causing these neurotransmitters to accumulate at postsynaptic receptor sites, resulting in intense vasoconstriction, acute arterial hypertension, and tachycardia.
The drug is metabolized primarily by plasma and hepatic cholinesterases to water-soluble metabolites (benzoylecgonine and ecgonine methyl ester). The most commonly used urine test detects benzoylecgonine at a sensitivity of 300 ng/mL. The elimination half-life of the parent drug is approximately 4-5 hours. Cocaine metabolites can be detected in urine for 24-48 hours. Pharmacokinetics of peri-natal cocaine use are poorly studied, but cocaine is known to cross the placenta readily. It is thought that urine tests in neonates exposed to cocaine in utero may be positive for a similar time as they are in an adult, although benzoylecgonine has been detected in neonatal urine for up to 4 days.
Potentially lethal medical complications associated with cocaine use, directly or indirectly, seem attributable to the intense sympathomimetic effects of the drug. They include acute myocardial infarction, cardiac arrhythmias, rupture of the ascending aorta, cerebrovascular accidents, seizures, bowel ischemia, and hyperthermia.
Use or abuse of cocaine during pregnancy is a major risk factor for the mother and her unborn child. Most pregnant cocaine users are patients with unplanned pregnancies of uncertain gestational age who seek prenatal care late (if at all) and have poor nutrition. They also tend to be abusers of multiple drugs, including tobacco and alcohol. It seems clear that there is, at minimum, a risk of 25% for preterm birth and 20% for infants that are small for gestational age, but studies are confounded by the effects of poor health and use of other substances of abuse. Studies have indicated as much as a 10-fold increase in the risk of abruption, suggesting an increase from 0.1% among all pregnancies to a 1% risk among cocaine-exposed pregnancies. Neurobehavioral abnormalities in neonates exposed to cocaine in utero are well documented, especially the tendency for hyperirritability and an inability to respond appropriately to stimulation. A purported increased incidence of sudden infant death syndrome among cocaine-exposed infants was suggested but has not been confirmed. An increased frequency of certain congenital anomalies among cocaine-exposed neonates has been reported. These anomalies include congenital heart disease, intestinal atresias, cerebral infarction, brain cavitation defects, and genitourinary defects.
It is thought that the increased risk of congenital anomalies among cocaine-exposed infants is associated with cocaine-induced vasoconstriction, which may cause infarction, severe hypoxemia, and hypoperfusion that may interrupt normal morphogenesis. A pattern of anomalies termed the vascular disruption syndrome has been described. The mechanism of vascular disruption is supported by animal studies that showed dose-dependent decreases in uterine blood flow and marked fetal hypoxemia, hypertension, hypoperfusion, and tachycardia in experimental animals that were administered cocaine intravenously.
Clinical evaluation of obstetric patients should incorporate the following protocol, which the clinician should consider for both medical and legal reasons:
• All pregnant women should be asked about previous and current drug use at the time of the first prenatal visit.
• The life-threatening implications of cocaine use during pregnancy for the patient and for her infant should be clearly explained to the pregnant woman admitting to cocaine use. She should be offered support services to aid in her abstinence.
• Continued abstinence from the use of cocaine should be reinforced and encouraged. Periodic urine testing for metabolites of cocaine is one way to discourage relapse in a pregnant woman admitting to cocaine use before or during pregnancy. The requirements for consent may vary from state to state.
• Urine testing of the mother, the neonate, or both may be useful in some clinical situations, such as unexplained fetal growth restriction, unexpected prematurity, or abruption in a woman not known to have hypertensive disease, even when cocaine abuse has not been previously suspected. The mother’s consent may need to be obtained before testing.
• Physicians should be familiar with their own state laws regarding consent for drug screening of pregnant women and newborns.
• Some state laws consider in utero drug exposure a form of child abuse or neglect and require the reporting of positive drug tests in pregnant women and newborns. Physicians should be familiar with state laws regarding testing and reporting.
Alcohol
Maternal alcohol ingestion during pregnancy may result in a recognizable pattern of congenital anomalies known as fetal alcohol syndrome. Fetal alcohol syndrome features include prenatal and postnatal growth restriction, characteristic facial anomalies (ie, short palpebral fissures, microphthalmia, indistinct or absent philtrum, thin upper lip, midfacial hypoplasia), microcephaly, joint contractures, and cardiac defects. Fetal alcohol syndrome is associated postnatally with mental retardation, hyperactivity, and developmental delays. Alcohol abuse during pregnancy is a leading cause of mental retardation. Maternal alcohol abuse is also associated with an increased risk of spontaneous abortion.
It is difficult to correlate the amount of alcohol consumed to the risk of fetal alcohol syndrome. Among pregnant women who consume four or more drinks per day during pregnancy, the risk for fetal alcohol syndrome may be as high as 20%, with risks increasing to perhaps 40% with six drinks per day. Women who have eight or more drinks per day are at significant risk (perhaps 60% or higher) for giving birth to an infant with fetal alcohol syndrome. The American Medical Association has stated that any woman who consumes four or more alcoholic drinks per day during pregnancy is significantly endangering the health of her unborn child. One beer, one shot of liquor, one mixed drink, and one glass of wine all contain the same amount of alcohol, approximately 0.5 oz of absolute alcohol. Thus, all forms of alcohol are equally hazardous. Risks associated with binge drinking are unknown but are likely to be substantial. No quantifiable risk has been associated with an occasional alcoholic beverage during pregnancy, but prudent medical advice is for pregnant women to avoid alcohol consumption completely.
Drugs and Chemicals Associated with Birth Defects
Tobacco
Smoking tobacco poses a threat to reproductive function and pregnancy outcome in women. The prevalence of smoking among adults has decreased from approximately 40% in 1965 to approximately 25% in the 1990s, with a similar decrease among women of reproductive age.
Stop smoking
The pregnant smoker may be at increased risk for the spontaneous abortion of an otherwise normal fetus, fetal death associated with placental abruption or placenta previa, preterm delivery, and PROM. A dose-response relationship has been shown between the amount of maternal smoking and reduced birth weight. The offspring of women who smoke approximately 20 cigarettes (one pack) per day during pregnancy have birth weights that are approximately 200 g less than those of infants born to women who do not smoke. If a woman stops smoking during the last 4 months of pregnancy, the risk of delivering a baby with lowered birth weight is similar to that of a nonsmoker. The use of smokeless tobacco also increases blood nicotine levels to levels comparable to those associated with cigarette smoking and, based on limited data, may result in similarly decreased birth weight. The possible clinical effects of passive smoking during pregnancy have not been clearly established.
Occupational and Environmental Agents
Pregnant women may be occupationally or environmentally exposed to a variety of chemicals that are associated with poor reproductive outcomes, including spontaneous abortion, low birth weight, neurologic abnormalities, and congenital anomalies. These chemicals include methyl mercury, lead, polychlorinated biphenyls, polybrominated biphenyls, and organic solvents. Verified human teratogens in this class of agents include methyl mercury and organic solvents. Lead is associated with growth restriction and myelination defects but not gross congenital anomalies. Polychlorinated biphenyls and polybrominated biphenyls are associated with skin discoloration and stillbirth.
Ionizing Radiation
Embryonic or fetal radiation exposure usually results from diagnostic radiologic studies. Diagnostic radiation usually exposes the conceptus to less than 5 cGy (5 rads), depending on the number of radiographs taken and the maternal site examined (Table 6). Any woman who is considering pregnancy and who is exposed to ionizing radiation on the job may wish to have her film badge evaluated more frequently to monitor radiation exposure. She should also wear a badge over the pelvic area for a more precise estimate of potential fetal exposure.
Thyrotoxic (therapeutic) radioisotope (131I) exposure is considerably more hazardous to the fetus than diagnostic studies that use iodine I 121. The fetal thyroid is not susceptible to radioisotope damage before 9-11 weeks of gestation. Dosimetry calculations should be made by experienced professionals, and risks may then be estimated based on isotope and biologic half-lives of the specific agents used and gestational timing of the exposure. Generally, the use of radioisotopes should be avoided during pregnancy. Risks associated with radioisotope iodine exposure during pregnancy include microcephaly, fetal growth restriction, goiter, and hypothyroidism. Risks to the infant include mental retardation and stunted physical growth.
Lithium
Lithium may produce malformations in 1% of offspring exposed prenatally. The anomalies frequently involve the heart and great vessels, with Ebstein’s anomaly of the tricuspid valve being observed most frequently. The concern regarding lithium exposure is the potentially lethal cardiac defect that occurs at a rate of 1 per 20,000. Exposure late in pregnancy may produce transplacental lithium intoxication with neonatal cyanosis, hypotonia, bradycardia, goiter with hypothyroidism, diabetes insipidus, and polyhydramnios. Additionally, maternal diuresis warrants perinatal dose adjustment to avoid lithium toxicity to neonate and mother.
Diethylstilbestrol
The synthetic estrogen diethylstilbestrol produces structural defects of the genital tract, as well as reproductive problems in prenatally exposed females. Vaginal adenosis has been detected in more than 50% of women whose mothers took this drug before the ninth week of pregnancy. A small percentage of women exposed in utero may develop clear-cell adenocarcinoma of the vagina. A variety of abnormalities of the genitourinary tract have also been observed in as many as 25% of males exposed in utero.
Vitamin A and Its Congeners
Isotretinoin. The vitamin A isomer isotretinoin is a potent teratogen, with serious congenital anomalies reported among approximately 35% of exposed fetuses. The specific congenital anomalies observed after oral administration of isotretinoin during early pregnancy include heart disease, thymic agenesis, microphthalmia, hydrocephalus, microtia, cleft palate, deafness and blindness, and an increased risk of spontaneous abortion.
Tretinoin. Topical tretinoin does not result in an increased risk of congenital anomalies because skin metabolizes the drug and no detectable systemic concentrations result.
Etretinate. Etretinate is an oral agent used to treat psoriasis. Case reports link the use of this agent to birth defects similar to those observed after the use of isotretinoin during pregnancy. Unlike vitamin A and its congeners, etretinate has been detected in serum of patients at therapeutic levels for as long as 7 years after cessation of use. Infants with congenital anomalies similar to those observed with isotretinoin use have been seen when the mothers had ceased use of etretinate up to 18 months before conception.
Drugs and Chemicals Associated with Birth Defects
High-Dose Vitamin A. The Centers for Disease Control and Prevention recently evaluated the use of vitamin A during pregnancy. Daily supplementation with 5,000 IU of vitamin A should be considered the maximum intake before and during pregnancy. A recent report associated maternal use of 15,000 IU or more of this nutrient during pregnancy with a significant risk (about triple the background) of congenital anomalies (eg, renal, craniofacial). This is of particular concern because some nutritional supplements contain 25,000 IU or more in a single dose.
Hormonal Agents
Danazol and other androgenic hormone agents may produce clitoral enlargement or labioscrotal fusion in the female fetus when they are given before 13 weeks of gestation. Recent studies, however, have failed to demonstrate a significant relationship between congenital anomalies and first-trimester use of oral contraceptive agents or medroxyprogesterone acetate.
Anticoagulants
Warfarin and other coumarin-derived anticoagulants inhibit the synthesis of vitamin K-dependent coagulation factors, and use during gestation can produce major and minor congenital anomalies in as many as 25% of fetuses exposed during the first trimester. Abnormalities characteristic of warfarin include hypoplastic nose, epiphyseal stippling, optic atrophy, microcephaly, IUGR, and other central nervous system anomalies. Heparin and low-molecular-weight heparin are not associated with an increased frequency of congenital anomalies.
Antithyroid Drugs
Thyroid medications such as propylthiouracil, methimazole, and iodide cross the placenta and may occasionally produce transient fetal hypothyroidism and goiter. Infants exposed to methimazole in utero also may develop scalp defects, but this association is rare. Thyroid replacement therapy (ie, thyroxine) does not cross the placenta and is not associated with congenital anomalies, fetal abnormalities, or neonatal abnormalities.
Anticonvulsants
Each of the commonly used anticonvulsant medications has been implicated as teratogenic, but there is no clear consensus concerning which one has the most teratogenic potential. Diphenylhydantoin may produce a syndrome characterized by abnormal facies, microcephaly, growth deficiency, mental retardation, and hypoplastic nails and distal phalanges in as many as 10% of exposed offspring. However, as many as 30% of exposed newborns may demonstrate some aspects of the syndrome. Intrauterine exposure to diphenylhydantoin is also associated with a three- to fourfold increase in the incidence of cleft lip or cleft palate and congenital heart disease. Mild to moderate mental retardation is observed in two thirds of children who have the most severe malformations associated with the syndrome. The syndrome was recently linked to lowered maternal epoxide hydrolase activity, an enzyme involved in the metabolism of hydantoin.
Drugs and Chemicals Associated with Birth Defects
Both valproic acid and carbamazepine have been associated with NTDs. Exposure during embryogenesis poses approximately a 1% risk of spina bifida to exposed fetuses. Specific syndromes have been described.
Trimethadione and paramethadione have been associated with abnormalities similar to those observed with the hydantoins. The risk for congenital anomalies or spontaneous abortion is 60-80% with first-trimester exposure. A syndrome including V-shaped eyebrows, low-set ears, high arched palate, and irregular dentition was identified.
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