The FRC is the volume of gas present in the lung at end-expiration during tidal breathing. It is composed of ERV and RV. This is usually 30-35 ml/kg, or 2100-2400ml in a normal-sized person. It represents the point where elastic recoil force of the lung is in equilibrium with the elastic recoil of the chest wall, i.e. where the alveolar pressure equilibrates with atmospheric pressure. The measurement of FRC is an important starting point for the measurement of other lung volumes, and its decrease has consequences for gas exchange and lung mechanics
Paracetamol is an antipyretic and analgesic grouped with NSAIDs because it is a COX inhibitor. However its effects may be mediated by a variety of other mechanisms. From the point of view of the CICM exam candidate, the most interesting thing about paracetamol is its toxicity.
The liver is central to the biotransformation of drugs. Clearance of ingested drugs (first-pass metabolism) and clearance of circulating drugs depends on the affinity of hepatic enzymes for these drugs, which in turn influences their hepatic extraction ratio. Pharmacokinetics are also influenced by the hepatic synthesis of carrier proteins. Liver disease has significant implications for both pharmacokinetics and pharmacodynamics.
The liver is responsible for producing 90% of the plasma proteins (basically everything that is not an immunoglobulin). It is an endocrine organ, responsible for the production of growth factors (eg. thrombopoietin), hormone transporters (eg. SHBG) and prohormones (angiotensinogen). It also produces macronutrients: glucose, by gluconeogenesis, amino acids by biosynthesis, and triglycerides from free fatty acids. It is also the major site of ketone synthesis. The liver is responsible for 50-8% of the total cholesterol synthesis, and for the synthesis of bile acids from cholesterol. Synthesis of urea from ammonia occurs in the liver, and synthesis of bilirubin occurs in hepatic Kupffer cell macrophages.
Ammonia is a toxic metabolite of protein and purine synthesis which mainly causes neurological dysfunction and cerebral oedema. It is mainly eliminated by the urea cycle enzymes, of which only hepatocytes have the complete set.
Agents which increase the motility of the gut include agents which increase the volume of stool, or just its water content, of those which decrease its viscosity or resistance. Prokinetic and stimulant laxatives also encourage peristalsis and increase intestinal secretions. An unavoidable side effect of most of these is the loss of water volume or electrolytes and the malabsorption of drugs and nutrients.
The liver is central to the metabolism of carbohydrates, lipids and protein. To summarise the metabolic role of the liver, one could safely say that it does everything of importance, as far as the transformation and regulation of metabolic fuels is concerned. It stores and regulates the release of carbohydrate, it directs traffic in the metabolic fates of fat, it degrades circulating plasma protein, and it is the sole processor of ammonia which is produced by amino acid deamination. It is also the destination for lactate, which it converts back to glucose as a mechanism of transferring metabolic energy to glycolysis-dependent tissues.
Urea and glucose are both filtered freely by the glomerulus. Glucose is a nutrient and every effort is made to reclaim it in the proximal tubule (100% recovery is the goal). This occurs by a saturable SGLT2-mediated co-transport with sodium. Urea, on the other hand, is a waste product. A minimum of urea is reabsorbed (mainly to maintain a high inner medullary concentration for water recovery), and the rest is concentrated in the urine and eliminated.
Vasopressin is an endogenously available vasoconstrictor with antidiuretic effects. "Vasopressor effects are exerted by V1 receptors, which are Gq-protein coupled receptors. Similarly to alpha-1 receptors, they increase intracellular calcium by means of increasing cAMP concentrations. V2 receptors are Gs-coupled receptors and produce the insertion of aquaporins into the apical membrane of principle cells of the collecting tubule, promoting the retention of watr.
Unlike catecholamine receptors, vasopressin receptors do not lose their affinity for vasopressin with changing pH."
Bilirubin is a product of haem metabolism, a tetrapyrrole molecule that can be a helpful antioxidant under normal conditions, or an oxidant neurotoxin when it is present in excess. It is metabolised by glucuronide conjugation in the liver, and then excreted into the bile.
The biliary tree consists of a series of ducts, mostly lined with cholangiocytes, which extend from the liver to the duodenum (where they empty via the sphincter of Oddi). This tree has approximately 10 ramifications, ranging from the 1-2μm biliary canaliculi where bile is first secreted to the 4-7mm common bile duct. Apart from the gallbladder, none of these structures are capable of contraction or peristalsis. Cholangiocytes which line this system are an epithelial cell species responsible for the secretion and modification (concentration, alkalinisation) of bile.
The liver is an essential excretory organ, and is able to eliminate substances from the body by excreting them in the bile. It excretes bile acids (most of which are reabsorbed), cholesterol, bilirubin, heavy metals, some drugs, and ions (mainly sodium). Additionally, it plays a dominant role in transforming poorly water-soluble drugs into more easily eliminated forms, preparing them for renal excretion.
Opioids are analgesic agents which act on opioid receptors, G-protein coupled receptors mainly situated on the presynaptic membrane. Activating these receptors increases potassium conductance and decreases calcium conductance. The net effect of their activation is to hyperpolarise the membrane and prevent neurotransmitter release.
Their mechanism of analgesic action is mainly related to the inhibition of glutamate release from primary pain afferent neurons in the spinal cord.
Diffusion describes solute transport across a semi-permeable membrane generated by a concentration gradient. The major determinant of diffusion rate in dialysis is the concentration gradient; however several other factors influence the rate of diffusion. These factors include the characteristics of the membrane, the temperature of the solution, the available surface area and the diffusivity coefficient of the molecule (which is a complex composite measure of how fast a substance diffuses across a solvent volume, expressed in length squared per second).