This is a summary of sepsis and infectious diseases trials and guidelines, aimed at the CICM Part 2 exam candidate. The objective was to list the important studies, link to an authoritative analysis, and produce a pithy one-liner to help remember the main points.
The tension generated by a sarcomere depends on the length of the sarcomere, and there is an optimal length at which tension is maximal, which in humans is ~2.7 µm. This is because of filament interactions: the greater the overlap between actin and myosin, the greater the force of contraction. As the filaments are pulled apart further, fewer of them are in contact, and less force can be generated. When the filaments lose contact altogether, the tension generated by the muscle is zero.
Excitation-contraction coupling is the series of events that link the sarcolemma action potential to muscle contraction and relaxation. It consists of several steps: action potential arrival, opening of voltage-gated calcium channels, release of calcium from the sarcoplasmic reticulum in response to this, and calcium-mediated disinhibition of regulatory proteins that control the mechanical act of myosin-actin crossbridge cycling. To relax, all the calcium must be returned to its stores in the sarcoplasmic reticulum.
The neuromuscular junction is a synapse for the transmission of a signal from the motor nerve terminal to a postsynaptic region on the muscle fibre. It is the archetypal synapse, in the sense that it is so easy to identify and study that a lot of our understanding of synaptic neurotransmission comes from studies of neuromuscular synapses. The main molecular protagonist is acetylcholine, and it has a very short role with no lines. Within one millisecond it is degraded by acetylcholinesterase, the target of many interesting drugs (neostigmine, organophosphates, nerve gases and nootropic agents).
Muscle tissue is classified into striated (skeletal and cardiac) vs smooth muscle tissue according to the arrangement of the contractile proteins, or lack thereof. Striated muscle organises actin and myosin into sarcomeres where these proteins are regularly spaced, whereas in smooth muscle these elements are organised into a more flexible arrangement that favours a larger range of possible lengths.
APRV has never come up in the CICM exams, and may never come up, because it would be unfair to test the candidates on something even the examiners themselves have little understanding of. It is a promising but poorly researched strategy that maximises alveolar recruitment and embodies the main principles of open-lung ventilation for ARDS.
The power of ventilation is defined as the work over time, and is normally 2-3 J/min. All other lung-protective strategies (low tidal volumes, low driving pressures) are ultimately all aspects of the same equation, i.e. all these strategies converge in their aim to reduce the power of mechanical ventilation
Dialysis for the severely hyponatremic patient can be a) avoided, b) delayed, c) underdosed, or d) performed with a "hacked" set of dialysate bags which have been altered to contain a lower concentration of sodium. Another option, which is easier and less satisfying, is to administer free water systemically in the form of 5% dextrose.
Dialysis disequilibrium syndrome is cerebral oedema resulting from the rapid removal of urea, and the resulting osmotic movement of water into CNS tissue. It has clinical manifestation similar to other forms of cerebral oedema and is treated in the same way (eg. with osmotherapy). Slower gentler dialysis is the most important preventative measure.
Body water content is regulated mainly by vasopressin. Circumventricular organs sense tiny (<3 mOsm/kg) changes in tonicity and modulate the release of vasopressin from the posterior pituitary, which results in the increased or decreased expression of aquaporins at the cortical collecting duct, where water is reabsorbed. This way urinary concentration mechanisms can be used to modify the loss of body water. The same hypothalamic control centre activates the sensation of thirst and affects behaviour to increase water intake.
Vasopressin is a nonapeptide, and its analogues are various modifications of that same basic molecular structure, used to change the pharmacokinetics and receptor selectivity of the end product. Terlipressin is a prodrug for lysine vasopressin which has a higher selectivity for V1 receptors, making it an almost pure vasopressor, and desmopressin (DDAVP) has a higher selectivity for V2 receptors, making it a more pure antidiuretic.
Numerous chemically diverse classes of oral hypoglycemic agents with various mechanisms of action exist, including biguanides, sulfonylureas, α-glucosidase inhibitors, meglitinides, thiazolidinediones, DPP-4 inhibitors, and SGLT-2 blockers. Unsurprisingly, for the majority of these (with some exceptions), hypoglycaemia is the most clinically important adverse effect.
Regular human insulin (eg. Actrapid) is an exact duplicate analog of the human peptide hormone, consisting of 51 amino acids. Other insulin variants modify the normal molecule to adjust the self-association behaviour of the drug, leading to longer or shorter absorption from the subcutaneous depot.