In hypernatraemic dehydration the increase in osmolality of the extracellular fluid results in
movement out of the cells so that intracellular fluid volume is depleted and depletion of extracellular fluid is less than expected. The objectives of therapy should be to treat the volume depletion and correct electrolyte imbalances slowly. Rapid correction of sodium can lead to seizures. Subdural effusions not haematomas are a recognised complication.
Somatostatin has various significant effects on the gastrointestinal tract: it inhibits the release of several gastrointestinal hormones, blocks the exocrine function of the stomach and the pancreas, and decreases the motility of both the stomach and the gut. Its physiological effects make it potentially useful in the therapy of various gastrointestinal diseases and disorders. Somatostatin is effective in the management of active variceal bleeding and increases the effectiveness of sclerotherapy. The somatostatin analogue octreotide has a definitive role in the medical management of hormone-secreting neuroendocrine tumours of the gut. GH- releasing hormone (GHRH) and somatostatin (SS) exert stimulatory and inhibitory influences respectively, on growth hormone.
Endothelin is produced by vascular endothelial cells and functions as a potent vasoconstrictor. 1,25-Dihydroxycholecalciferol is the physiologically active form of vitamin D. It is formed primarily in the kidney by enzymatic hydroxylation of 25 hydroxycholecalciferol. ANP is a potent natriuretic and vasodilatory peptide but is secreted by the heart atria. Somatomedin is an insulin-like polypeptide made by the liver and some fibroblasts. Angiotensin II is the active form of angiotensin; it is an octapeptide produced and found in blood and is synthesized from angiontensin.
The main enzyme that cleaves Angiotensin I to Angiotensin II is called Angiotensin-converting enzyme and is found predominantly in the lungs. This enzyme is a target for drugs (ACE inhibitors) that inactivate it, decreasing the rate of angiotensin II production. Angiotensin II has a number of effects throughout the body including: It is a potent direct vasoconstrictor leading to an increase in blood pressure. It also potentiates the release of norepinephrine by a direct action on postganglionic sympathetic fibres. Angiotensin II acts on the brain to increase the sense of thirst and increases the secretion of vasopressin and ACTH. It acts on the adrenal cortex, causing it to release aldosterone. It has a direct effect on the kidney to increase the glomerular filtration rate by increasing the renal perfusion pressure.proximal tubules and to increase sodium resorption. Angiotensin II is degraded by angiotensinases that are located in red blood cells and the vascular beds of most tissues, and has a half-life in humans of 1-2 minutes. It is degraded to Angiotensin III. During the metabolic response to trauma, there is increased secretion of catecholamines, cortisol, glucagon and growth hormone. The first three of these tend to increase blood glucose concentration; catecholamines, cortisol and glucagon act directly, whereas growth hormone appears to potentiate the action of cortisol and opposes the action of insulin. Adrenaline and glucagon act most rapidly, by stimulating glycogenolysis; cortisol tends to act more slowly, through the stimulation of gluconeogenesis. Insulin is a hypoglycaemic hormone. C-reactive protein is a marker of inflammation, but does not affect glucose homeostasis. About 100 ml of mucus is produced every day. The cilia are under the control of a physiological motor, dynein (which is absent in Kartageners syndrome). The mucociliary escalator moves at 2 cm/minute. The bronchioles do not have cartilage in their wall (which distinguishes them from bronchi). The bronchioles can be up to 1 mm in diameter. The combination of female phenotype on external examination with 46XY karyotype is typical of complete androgen insensitivity syndrome, which is caused by a mutation that prevents the binding of androgens to the androgen receptor. A failure of testosterone secretion alone in a 46XY individual usually results in an ambiguous phenotype; this may also occur with a failure of conversion of testosterone to dihydrotestosterone (DHT) (5a-reductase deficiency): the development of the male external genitalia in utero is largely dependent on DHT. However, in this condition, masculinisation may occur at puberty as a result of the increased secretion of testosterone. Neither an abnormal secretion of FSH or prolactin causes this presentation.
Oxidation of fatty acids occurs in the mitochondria. The transport of fatty acyl-CoA into the mitochondria is accomplished via an acyl-carnitine intermediate, which itself is generated by the action of carnitine acyltransferase I, an enzyme that resides in the outer mitochondrial membrane. The acyl-carnitine molecule is then transported into the mitochondria where carnitine acyltransferase II catalyses the regeneration of the fatty acyl-CoA molecule. Deficiencies in carnitine lead to an inability to transport fatty acids into the mitochondria for oxidation. This can occur in newborns and particularly in pre-term infants. Carnitine deficiencies are also found in patients undergoing haemodialysis or exhibiting organic aciduria. Carnitine deficiencies may manifest systemic symptomatology or may be limited to only muscles. Symptoms can range from mild occasional muscle cramping to severe weakness or even death. Treatment is by oral carnitine administration. The luteal stage lasts from day 15 to day 28 of the menstrual cycle. The follicular stage lasts from day 1 to 14 of the menstrual cycle. Rising levels of oestrogens occur during the follicular stage. Rising levels of oestrogens cause an increase in the production of luteinising hormone- releasing hormone (LHRH) and a reduction in the production of follicle stimulating hormone- releasing hormone (FSHRH). The zona glomerulosa of the cortex is predominantly responsible for mineralocorticoid production, the zona fasciculata for glucocorticoid production and the zona reticularis for sex corticoid production. The adrenal medulla originates from the neural crest and hence there is almost complete demarcation of function, with the medulla being responsible for the production of catecholamine-related compounds. Low-frequency waves are detected in the scala tympani, high-frequency waves are detected in the scala vestibuli. Both contain perilymph. The scala media is filled with potassium-rich endolymph. Normal hearing frequency ranges from 20 to 20,000 Hz. The scala media contains the organ of Corti The measurement of faecal fat excretion (now regarded as obsolete by many physicians) is a test for malabsorption, but it does not distinguish between its possible causes. The pancreolauryl test can be abnormal in pancreatic or biliary disease. Breath hydrogen excretion is increased with increased bacterial activity in the gut, but this can be a cause of malabsorption (colonisation of the small gut causes deconjugation of bile salts) and also a consequence (fermentation of unabsorbed nutrients in the large intestine). The absorption of xylose may be decreased in various small intestinal diseases. The lactose tolerance test, in which the rise in blood glucose following a test dose of lactose is compared with that following a test dose of glucose, is, however, specific for lactase deficiency (though definitive diagnosis is by measurement of the enzyme in a biopsy sample). Furosemide is a loop diuretic. Metolazon (a thiazide like diuretic) inhibits Na + and Cl - transport in the cortical thick ascending limb and early distal tubule. Mannitol is a non-metabolizable osmotic diuretic and is filtered into the tubular space where it markedly increases tubular fluid osmolality. Spironolactone is a competitive antagonist of aldosterone. Therefore it blocks aldosterone-stimulated Na + reabsorption and K + and H + excretion in the late distal tubule and collecting duct.
2-adrenoreceptor agonists have effects on smooth and skeletal muscle, including bronchodilatation, relaxation of the uterus and tremor. 2-agonists also have mild anti- inflammatory action. 2-agonists enhance mucociliary clearance and have metabolic effects such as raising free fatty acid, glucose and insulin concentrations. Hypokalaemia also occurs commonly, especially following intravenous administration, and is thought to be related to linkage of 2-receptors to Na+/K+-ATPase. 1-receptors agonism causes an increase in heart rate and myocardial contractility.
The insulin-like growth factors (IGF-I and IGF-II; IGFs) share 50% homology with insulin. Both are present in human serum with molecular sizes of approximately 7.6 kDa. IGFI, previously known as somatomedin-C, is a basic peptide of 70 amino acids. The liver is a major site of expression, although almost all tissues express these peptides. IGF-I is an important postnatal growth factor and its concentration increases at term and postnatally.
In human infants suffering from intrauterine growth retardation. IGF-I concentrations are lower than in age-matched controls and in macrosomic infants of diabetic mothers, circulating levels of IGF-I are elevated.
The primary endocrine factors mediating the pubertal growth spurt are sex steroids and growth hormone. Increasing sex steroid production stimulates increased amplitude of growth hormone secretion at puberty, with subsequent increased production of IGF-I.
Patients with primary hyperaldosteronism will have an increased aldosterone production associated with a decreased renin. Patients with secondary hyperaldosteronism (caused by kidney disease or renal vascular disease) will have increased plasma levels of renin and aldosterone. Diuretic therapy may enhance renin release probably because of diuresis/natriuresis . Beta blockers slow down the release of renin from the kidneys. Deficiency of red cell glucose 6-phosphate dehydrogenase is a common inherited disorder, which renders red cells susceptible to increases in oxidative stress. Antimalarial drugs are among several that can cause haemolysis by increasing oxidative stress in such patients, although many different mutations in the enzyme have been described, and the range of clinical severity is wide. Glucose 6-phosphatase deficiency is the cause of type-1 glycogen storage disease. Pyruvate kinase deficiency is a rare cause of haemolytic anaemia. Decreased activity of bilirubin glucuronyltransferase can cause unconjugated hyperbilirubinaemia (eg Gilberts syndrome, CriglerNajjar disease); because the excess bilirubin is unconjugated, there is no bilirubin in the urine. Deficiency of hydroxymethylbilane synthase is the cause of acute intermittent porphyria. During acute attacks, the urine darkens on standing but there is no jaundice. Quinine-like antimalarials do not precipitate acute attacks of porphyria in susceptible patients.
Prostaglandins (PGs) are biosynthesised from straight-chain C20 fatty acids, arachidonic acid being the precursor. The responsible enzyme is cyclooxygenase, leukotrienes are formed by lipoxygenase. Glucocorticoids and aspirin inhibit the prostaglandin synthesis. Prostaglandins lead to vasodilatation. The amounts of PGs in the tissues are very low, indicating that they are biosynthesised immediately before hormone-stimulated release. PGs seem to be metabolised by all body tissues. The chemoreceptors that regulate respiration are located both centrally and peripherally. Normally control is exercised by the central receptors located in the medulla, which respond to the CSF hydrogen ion concentration, in turn determined by CO 2 , which diffuses freely across the blood-brain barrier from the arterial blood. The response is both quick and sensitive to small changes in arterial CO 2 (PaCO 2 ). Whilst central chemoreceptors are therefore (indirectly) sensitive to levels of carbon dioxide, peripheral chemoreceptors are also highly sensitive to oxygen. There are three clusters of peripheral chemoreceptors: the aortic body located in the wall of the arch of the aorta, and the two nodular carotid bodies in the left and right common carotid arteries. When the concentration of carbon dioxide in the blood rises, a condition known as hypercapnia, the central and peripheral chemoreceptors stimulate the inspiratory areas to stimulate the rate and depth of breathing. This hyperventilation causes more carbon dioxide to be exhaled until levels return to normal. Clearance is calculated using the formula (U V)/P where U = urine concentration in mg/ml, V = urine production in ml/min, P = plasma concentration in mg/ml.
Gas exchange can occur in the final seven branches of the bronchoalveolar tree (the respiratory zone). The first 16 branches of the bronchial tree are collectively known as the conducting zone. The equilibration of gases takes about 0.25 s in the resting lung. Only about 1.5% of oxygen is carried in solution in the plasma. Carbon dioxide is more water-soluble than oxygen, between 5 and 10% of and this is the predominant method of carriage of CO 2 is carried in dissolved form. During exercise, increased oxygen consumption and increased venous return to the heart result in an increase in cardiac output and an increase in blood flow to both skeletal muscle and coronary circulation, when oxygen utilisation is greatest. The increase in cardiac output is due to an increase in both heart rate and stroke volume. Systemic arterial pressure also increases in response to the increase in cardiac output. However, the fall in total peripheral resistance, which is caused by dilatation of the blood vessels within the exercising muscles, results in a decrease in diastolic blood pressure. The pulmonary vessels undergo passive dilatation as more blood flows into the pulmonary circulation. As a result, pulmonary vascular resistance decreases. The decrease in venous compliance, caused by sympathetic stimulation, helps to maintain ventricular filling during diastole. The alveoli at the apex of the lung are larger than those at the base so their compliance is less. Because of the reduced compliance, less inspired gas goes to the apex than to the base. Also, because the apex is above the heart level, less blood flows through the apex than through the base. However, the reduction in air flow is less than the reduction in blood flow, so that the V/Q ratio at the top of the lung is greater than it is at the bottom. The increased V/Q ratio at the apex makes PaCO 2 lower and PaO 2 higher at the apex than they are at the base. Growth hormone (GH) is synthesised, stored, and secreted by the endocrine cells of the anterior pituitary. Its release is stimulated by growth hormone-releasing hormone and inhibited by somatostatin. Numerous factors serve as a stimulus for GH release, including hypoglycaemia (e.g. insulin administration), moderate to severe exercise, stress due to emotional disturbances, illness, and fever, and dopamine agonists such as bromocriptine.
The history is typical of hypoglycaemia. Blood glucose concentration is maintained in the fasting state through glucose release from glycogen (glycogenolysis) and gluconeogenesis (glucose synthesis from lactate and other precursors). Glycolysis consumes glucose: the activity of the glycolytic pathway is reduced during starvation, to conserve glucose, with complementary increases in the production and oxidation of ketones and fatty acids. Abnormalities of the tricarboxylic acid cycle are very rare and do not cause hypoglycaemia.