Assessment of proteinuria

Proteinuria is a strong predictor of adverse cardiovascular and kidney events, and an accurate assessment of proteinuria is important for the evaluation and management of CKD. Total urinary protein can be assessed using dipstick, precipitation, and electrophoresis methods. Urinary albumin, the predominant urinary protein in most proteinuric kidney diseases, can be assessed using an albumin-specific dipstick, immunochemical techniques, and size-exclusion high-performance liquid chromatography. Urine albumin may be immune-reactive, immune-unreactive, fragmented, and biochemically modified, and laboratory techniques have variable abilities to detect different types of albumin. Urine specimen for proteinuria assessment can either be obtained from a timed-collection or a spot urine sample. Spot urine protein- or albumin-to-creatinine ratios are preferred to a 24-hour urine sample in routine practice. Assessment of albuminuria rather than proteinuria is more clinically meaningful in patients with diabetic kidney disease, and proteinuria and albuminuria assessments both have a role in nondiabetic kidney disease and in general population screening. As measurement and sampling procedures for proteinuria assessment have yet not been standardized, it is important for physicians to be aware of different types of urinary proteins, albumins, laboratory techniques, and urine sampling methods.     

Pathophysiology of acne

Acne is a disease that develops in pilosebaceous follicles. Acne was long considered was an infectious disease related to Propionibac-terium acnes, but studies show that the production of inflammatory substances in situ was much more important to the action of this bacterium than was simple infection. It was once thought that only the androgens could stimulate the seba-ceous gland, but today we know that neuromediators can also stimulate sebum production. This finding provides physiological support to the clinical observation that stress can induce acne.     

Pathophysiology of spasticity

Lance's definition of spasticity focuses on the exaggeration of the tonic stretch reflex as one component of the upper motor neuron syndrome. In daily practice, many different symptoms are referred to as spasticity. Experimental studies stress the particular role of the premotor cortex and the medial reticular formation for the genesis of spasticity. Physiological studies clearly demonstrate the two components, phasic and tonic, of the stretch reflex. Whatever the pathology, the clinical picture of spasticity seems to depend less upon the etiology of the lesion and more upon its location in the neuraxis. There is a regional organisation of the spinal circuitry according to the function of the segmental nerves and, therefore, a particular clinical presentation related to each spinal segment. The muscular efferents are also heterogeneous and linked to function. This is the fundamental base of focal treatment of spasticity.     

Pathophysiology of ileus

OBJECTIVE: To review the endogenous alterations generating critical illness in bowel obstruction. DATA SOURCES: Own experimental and clinical investigations and relevant articles published in international literature. DATA SYNTHESIS AND CONCLUSIONS: Large bowel obstruction is mostly confined to the colon. Passive dilatation and increasing luminal pressure might cause local gut wall ischemia with impending perforation whereas hypovolemia is not actively induced. Mediators are not released. Bacterial translocation occurs with little clinical significance. High small bowel obstruction with quantitative reflux predominantly causes early and marked hypovolemia and electrolyte disorders. In low small bowel obstruction the bowel wall is reacting upon the abundant luminal proliferation of gram-negative endobacteria: Induction of mucosal hypersecretion is the main cause of hypovolemia. Systemic endotoxinemia beginning with the fourth postobstruction day induces a septic inflammatory response encouraging organ failure. Systemic prostacyclin liberation in long standing obstruction or following intraoperative manipulation might generate cardiopulmonary decompensation.     

Pathophysiology of asthma

Further insight into the inflammatory process of asthma has accumulated during the past few years. New inhalational anaesthetics seem to have a better bronchorelaxant effect, and prophylactic treatment with beta2-agonists and local anaesthetics may also be an alternative. Bronchospasm during anaesthesia appears to be less common now, but persons with asthma should still be considered to be at an increased risk of severe morbidity.     

Pathophysiology of pain

Pain is a major symptom of many different diseases. Modern pain research has uncovered important neuronal mechanisms that are underlying clinically relevant pain states, and research goes on to define different types of pains on the basis of their neuronal and molecular mechanisms. This review will briefly outline neuronal mechanisms of pathophysiological nociceptive pain resulting from inflammation and injury, and neuropathic pain resulting from nerve damage. Pain is the sensation that is specifically evoked by potential or actual noxious (i.e. tissue damaging) stimuli or by tissue injury. Pain research has not only explored the neuronal and molecular basis of the pain system of the healthy subject but has also provided insights into the function and plasticity of the pain system during clinically relevant pains such as post-injury pain, inflammatory pain, postoperative pain, cancer pain and neuropathic pain. This review will briefly describe the pain system and then address neuronal mechanisms that are involved in clinical pain states.     

Pathophysiology of pain

Clinically relevant pain states are usually characterized as either inflammatory or neuropathic. While inflammatory pain results from tissue injury or damage, neuropathic pain results from damage or disease of nerve fibers. In either pain state, both the peripheral and the central nociceptive system contribute significantly to the generation of pain. During inflammation peripheral nociceptors ("pain fibers") are sensitized (peripheral sensitization), and upon nerve injury or nerve disease peripheral nerve fibers develop ectopic discharges originating from the site of the nerve lesion or the cell body of damaged fibers. As a consequence a complex neuronal response is evoked in the spinal cord where neurons become hyperexcitable (central sensitization).Central sensitization is a neuronal process that amplifies the activity from the periphery. Numerous molecular mechanisms are involved in peripheral and central nociceptive processes including rapid functional changes of signaling (increase of excitability) and long-term regulatory changes such as upregulation of mediator/receptor systems. The conscious pain is generated by thalamocortical networks that produce both sensory discriminative and affective components of the pain response.     

Pathophysiology of polytrauma

Immediate and early trauma deaths are determined by primary brain injuries, or significant blood loss (haemorrhagic shock), while late mortality is caused by secondary brain injuries and host defence failure. First hits (hypoxia, hypotension, organ and soft tissue injuries, fractures), as well as second hits (e.g. ischaemia/reperfusion injuries, compartment syndromes, operative interventions, infections), induce a host defence response. This is characterized by local and systemic release of pro-inflammatory cytokines, arachidonic acid metabolites, proteins of the contact phase and coagulation systems, complement factors and acute phase proteins, as well as hormonal mediators: it is defined as systemic inflammatory response syndrome (SIRS), according to clinical parameters. However, in parallel, anti-inflammatory mediators are produced (compensatory anti-inflammatory response syndrome (CARS). An imbalance of these dual immune responses seems to be responsible for organ dysfunction and increased susceptibility to infections. Endothelial cell damage, accumulation of leukocytes, disseminated intravascular coagulation (DIC) and microcirculatory disturbances lead finally to apoptosis and necrosis of parenchymal cells, with the development of multiple organ dysfunction syndrome (MODS), or multiple organ failure (MOF). Whereas most clinical trials with anti-inflammatory, anti-coagulant, or antioxidant strategies failed, the implementation of pre- and in-hospital trauma protocols and the principle of damage control procedures have reduced post-traumatic complications. However, the development of immunomonitoring will help in the selection of patients at risk of post-traumatic complications and, thereby, the choice of the most appropriate treatment protocols for severely injured patients.     

Pathophysiology of pain

Progress in the knowledge of the pathophysiology of pain allow to associate clinical symptoms of painful syndroms to physiological, morphological and neurobiochemical changes observed both at peripheral and central sites. Thus, nociceptive pains involve both a sensitisation of nociceptors and a secondary central sensitisation. Numerous mediators are involved in these phenomena which reflect neuroplasticity. Peripherally, they come from plasma, immune cells and afferent fibres involved in neurogenic inflammation. Their number explains how the peripheral mechanisms of pain are complex and how it is difficult to pharmacologically suppress the activity of nociceptors. Other mediators are involved in the dorsal horn of the spinal cord. Excitatory amino acids are particularly involved by acting on NMDA receptors; substance P seems to work as a facilitatory neuromodulator rather than as a neurotransmitter. The mechanisms of neuropathic pains are different because both small and large diameter afferent fibers are involved. Ectopic discharges from lesional sites of C fibers, sprouting and abnormal neuronal connections have been described. Up regulation of ionic, especially sodic, channels has been demonstrated and could explain spontaneous discharges. Here again, central sensitisation is also observed but present knowledge does not allow to distinguish specific mechanisms. These progress in the knowledge of pathophysiology of pain allow to improve the understanding of the mechanism of action of analgesic drugs. They also give basis to the discovery of novel drugs with original mechanisms.     

Pathophysiology of sciatica

The exact pathophysiologic mechanisms behind sciatica are incompletely known; however, compression of spinal nerve roots is known to be correlated to both pain and neural dysfunction in a segmental distribution of that specific nerve root. Compression per se may impair the transport of nutrients to the nerve tissue in such a way that affects the nerve root function. There also might be a local affect on nerve roots or root sleeves by substances leaking from the degenerated intervertebral discs.