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.
This is an altered level of consciousness attributed to the consequences of acute or chronic liver failure. Ammonia is only one of the aetiological agents. But, it is certainly the one everyone always thinks of. Copious amounts of blood are being sent for ammonia levels every day. Surely, there must be some reason behind this. In order to derive some meaning from this seemingly mindless ammonia-lust, one must explore the mechanisms of metabolic derangement which arise within the liver failure patient.
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.
Tests of liver function include tests of liver enzymes which leak following hepatic injury, and tests of the synthetic and metabolic functions of the liver. Of the latter, albumin, glucose, bilirubin, ammonia and coaguilation studies are the most commonly used. In all cases, failure of liver function is not the only possible explanation for an abnormal biochemistry result.
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).
Frequently, the college will put some sort of horrible LFT picture up for the candidates and ask them to make sense of it. The general trend of questions seems to be coma, flavoured with a recent history of discharge from an alcohol rehab institution of some sort. There is one specific question which is frequently repeated where the ammonia is also elevated, and the LFTs are raised in a non-specific pattern. Give six differentials, they usually ask.
Heart failure management is a massive daunting topic. In order to approach this in a systematic manner, I have separated the problems of heart failure into the variables which govern cardiac output, and the means of manipulating those variables. The approach resembles that of the similar chapter from the section on cardiothoracic intensive care. The definitive resource for this is probably this 2013 guideline statement by the AHA/ACC. Unless otherwise reported, it is my source for most of the information below. For the sane exam candidate who may be disinclined to read the entire fifty-page document, of particular interest may be Section 7.3.2, Pharmacological Treatment for Stage C HFrEF.
The liver stores metabolic fuel as glycogen (which can be rapidly mobilised) and fat (which can be slowly mobilised). There may be 75-100g of glycogen (400 kcal) and up to 75g (675 kcal) of fat in a normal liver, with more fat being deposited in times of dietary carbohydrate excess. The liver also stores micronutrients such as fat-soluble vitamins (A, D, E and K), the water-soluble vitamin B12, iron (as ferritin and haemosiderin), and trace elements (zinc, copper, selenium, etc). The liver also acts as a venous blood reservoir used to buffer fluctuations in blood volume.