Pathophysiology of microcirculation in venous disease

Microcirculatory disturbances lead to chronic ulceration of the leg, and this symptom is a sign of a chronic venous insufficiency (CVI), caused by increased leg vein pressure and continous changes in vein pressure, which need medical treatment, and if a chronic capillary reaction present, treatment by applying a graduated compression bandage of the leg is mandatory. Subcutaneous tissue hypoxaemia and interstitial edema lead to worsening of the ulcer and need intensive and systematic wound care, because unhealed chronic wound with trophic changes of the skin is the major cause of further CVI changes of the leg. As chronic venous disease has complex etiologic basis, it needs diagnostics and treatment modality based on various approaches, and that microcirculatory pathophysiological approach should be considered in all kinds of the treatment of chronic venous insufficiency. Microcirculation pathology should be used as an approach in the treatment regiment of CVI, whilst the basic pathophysiology of the venous diseases, which is known as one of the causes of CVI. This approach will give better results of treatment and other pathologic disturbances which were caused by chronic vitious circle chain processes.     

Pathophysiology of radicular pain

Pathophysiological mechanisms of low back pain and radicular pain produced by lumbar disorders are still controversial. We have made experimental animal models and have elucidated the mechanisms of hyperalgesia, which is a pain related behavior, in these animals. We have not demonstrated that only mechanical compression of the nerve roots in the lumbar spine results in hyperalgesia in rat. We found that application of the nucleus pulposus to the nerve roots produces time-dependent reversible hyperalgesia in the affected hindpaw of the rat, and that the hyperalgesia is related to bioactive substances in the arachidonic acid cascade. We have also reported that inflammatory granulation tissue around the nerve root is related to hyperalgesia rather than the nucleus pulposus itself, and that mechanical compression to the nerve root after application of the nucleus pulposus produces different type of hyperalgesia. Collectively, not only mechanical compression of the cauda equina and nerve root but also various inflammatory substances are related to pathophysiological mechanisms of radicular pain in patients with lumbar disorders such as disc herniation. Elucidating pathophysiological mechanisms of pain-related behaviors such as hyperalgesia is important to establish a new strategy for the treatment of lumbar painful radiculopathy.     

脑静脉血栓形成的病理生理学和病因

脑静脉血栓形成(cerebral venous thrombosis, CVT)是指颅内静脉和静脉窦血栓形成,是一类少见的脑血管病类型.由于临床症状多样且无特异性,CVT的临床诊断比较困难.了解CVT的病理生理学和病因有助于理解其临床症状和影像学表现,并指导治疗.文章对CVT病理生理学和病因的相关研究进展进行了综述.     

Pathophysiology of Behcet's disease

SUBJECT: Pathophysiology of Beh?et's disease (BD) is complex. Recent experimental data shed new light on the mechanisms leading to organ lesions. MAIN ISSUES: Neutrophils and cytotoxic lymphocytes are now recognized as key effector cells in BD. Genetic susceptibility, environmental factors (virus and/or bacterial infections), inflammatory response abnormalities (heat shock proteins, dysregulated NO production) and abnormal immune response play also a major role in BD pathogeny. PERSPECTIVES: Better understanding of the BD pathophysiology will allow the development of new therapies more specific of BD.     

Pathophysiology of diverticular disease

Introduction: Inflammation of diverticula, or outpouchings of the colonic mucosa and submucosa through the muscularis layer, leads to diverticulitis. The development of diverticular disease, encompassing both diverticulosis and diverticulitis, is a result of genetic predisposition, lifestyle, and environmental factors, including the microbiome.

Areas covered: Previous reports implicated genetic predisposition, environmental factors, and colonic dysmotility in diverticular disease. Recent studies have associated specific host immune responses and the microbiome as contributors to diverticulitis. To review pertinent literature describing pathophysiological factors associated with diverticulosis or diverticulitis, we searched the PubMed database (March 2018) for articles considering the role of colonic architecture, genetic predisposition, environment, colonic motility, immune response, and the microbiome.

Expert commentary: In the recent years, research into the molecular underpinnings of diverticular disease has enhanced our understanding of diverticular disease pathogenesis. Although acute uncomplicated diverticulitis is treated with broad spectrum antibiotics, evaluation of the microbiome has been limited and requires further comprehensive studies. Evidence suggests that a deregulation of the host immune response is associated with both diverticulosis and diverticulitis. Further examining these pathways may reveal proteins that can be therapeutic targets or aid in identifying biological determinants of clinical or surgical decision making.     

Pathophysiology of diverticular disease

There is substantial evidence that colonic diverticulosis is related to civilization, industrialization and a "Western" lifestyle and diet, being described as "a disease of Western civilization". Its increased incidence during the 20th century and the morbidity and mortality associated with complications, demand that this condition should receive greater attention in terms of aetiology, prevention and management. It is generally believed that low dietary fibre and ageing are the two main pathogenic factors involved in this disease. Physiological studies have also demonstrated that there is a higher intraluminal pressure in the large bowel with diverticula.This chapter provides the evidence currently available for the pathophysiology of colonic diverticulosis and discusses its aetiological factors, including low dietary fibre, ageing and intraluminal pressure as well as extracelluar matrix such as collagen and elastin. The difference between the left-sided diverticulosis commonly seen in Caucasians and the right-sided predominantly observed in Asians is also presented.     

Pathophysiology of graft-versus-host disease

Complications of allogeneic hematopoietic stem cell transplantation (HSCT) remain barriers to its wider application for a variety of diseases. Graft-versus-host disease (GVHD) is the major cause of morbidity and mortality following allogeneic HSCT. GVHD can be considered an exaggerated, undesirable manifestation of a normal inflammatory mechanism, in which donor lymphocytes encounter foreign antigens in a milieu that fosters inflammation. Recent advances in the study of cytokine networks, chemokine gradients, and the direct mediators of cellular cytotoxicity have led to improved understanding of this complex syndrome. The pathophysiology of acute GVHD can be considered as a three-step process in which the innate and adaptive immune systems interact: (1) tissue damage to the recipient by the radiation/chemotherapy pretransplant conditioning regimen; (2) donor T-cell activation and clonal expansion; and (3) cellular and inflammatory factors. Here we review the immunologic interactions that cause clinical GVHD and discuss the risk factors and prophylactic strategies for acute GVHD according to this model.     

Pathophysiology in Microvillus inclusion disease

Microvillus inclusion disease (MID) is a congenital disorder with the clinical signs of watery diarrhea often beginning in the first days of life. The main pathological features of the disease include a villus atrophy and an accumulation of periodic acid-Schiff (PAS)-positive material within the apical cytoplasm of enterocytes on the light microscopy level. Electron microscopic criteria are pathognomonic consisting of an increased amount of secretory granules preferentially in crypt epithelial cells and of the presence of microvillus inclusion bodies (MIBs) which are most frequently found in villus enterocytes. Until now the basic molecular defects have not been disclosed completely. In this review we discuss the actual pathogenetic hypothesis and the therapeutic options besides small bowel transplantation.     

Pathophysiology of chest pain in patients with nutcracker esophagus

OBJECTIVES: Nutcracker esophagus is a manometric pattern that is commonly seen in patients with functional (noncardiac) chest pain. However, this pattern is often unassociated with pain. Consequently, the pathophysiology of chest pain in these patients is unclear. METHODS: We prospectively examined the sensory perception and biomechanical properties of the esophagus in 10 patients with chest pain and a nutcracker esophagus, along with those properties in 12 healthy controls using impedance planimetry. RESULTS: Stepwise balloon distentions reproduced typical chest pain in 9/10 (90%) patients. The threshold for chest pain was lower (p < 0.05) in patients than in controls (mean +/- SD 43+/-5 vs 62+/-4 cm H2O) but only 2/12 controls experienced pain. The thresholds for first perception and moderate discomfort were also lower (18+/-8 vs 30+/-11 cm H2O, p < 0.01 and 28+/-9 vs 62+/-5 cm H2O, p < 0.001) in patients than in controls, but only 3/12 controls experienced moderate discomfort. The esophageal reactivity to balloon distention was higher in patients than in controls (p < 0.001). The tension-strain curve shifted to the left in the patient group when compared to that in the controls (p < 0.05). CONCLUSIONS: Patients with a nutcracker esophagus demonstrate a hypersensitive and stiff esophagus. Because balloon distention reproduced their chest pain, visceral hyperalgesia of the esophagus may be relevant to the pathogenesis of their pain. Balloon distention test may be more useful in the evaluation of patients with functional chest pain and a nutcracker esophagus.     

Pathophysiology of atherosclerotic heart disease

Coronary atherosclerosis is the major health problem of the twentieth century. Although there has been a recent decrease in mortality from this condition in many Western countries, the incidence has remained the same, and coronary atherosclerosis continues to be the leading cause of death. Our understanding of the disease process has been steadily increasing; however, much still needs to be clarified. The clinical presentations of coronary artery disease are diverse and not clearly linked to the severity or extent of the disease. Patients with similar coronary lesions present variously with stable and unstable angina or myocardial infarction, and all too many have sudden death as the initial clinical presentation. Recently, much attention has focused on the initial events leading to the development of atherosclerotic plaques. Current concepts unite formerly opposed views on the roles of intimal injury, platelets, lipids, and monoclonal smooth muscle cell proliferation in initiating atherogenesis. Progress has been made in understanding the early structural and functional alterations caused by myocardial ischemia. This understanding is leading to the development of interventions such as intracoronary thrombolysis to prevent or limit permanent myocardial injury. Measures to prevent serious complications of ischemic heart disease such as infarct rupture, aneurysm formation, and ischemic cardiomyopathy are still needed.     

Pathophysiology of obstructive arterial disease

Intermittent claudication is due to ischemia of working muscles in patients with stenoses or obstructions of large or medium sized arteries. Arteriosclerosis obliterans is by far the most common etiology. As an arterial stenosis develops, the distal blood flow and blood pressure are not affected until a critical diameter occurs. Then, blood flow and blood pressure fall precipitously with further narrowing of the lumen area. The most important factors that influence blood flow and the blood pressure drop across a stenosis are the radius of the stenosis and of the artery, and the velocity of blood flow. The velocity of blood flow varies inversely with the peripheral resistance. A decrease in peripheral resistance which occurs with exercise, vasodilator drugs, or sympathectomy leads to an increased blood flow velocity and an increased pressure drop across a stenosis. Thus, a non-critical stenosis at rest can become critical and limit blood flow during exercise. In arterial occlusions and critical arterial stenoses, the distal perfusion pressure is decreased due to the high resistance of the small collateral vessels but blood flow may be normal at rest. With exercise, the distal perfusion pressure decreases to a lower level due to the fall in peripheral resistance. Then, the external pressure of muscle contraction may close the arterial bed and stop blood flow. The stimulus to collateral blood vessel development is not known but may involve the pressure differential across the involved vascular bed and metabolic products produced during the ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pathophysiology of ischemic heart disease

Recent clinical and experimental studies have helped to clarify the pathophysiology of acute and chronic coronary insufficiency, particularly in the area relating myocardial ischemia to abnormal function of the damaged left ventricle. When proximal vessel stenosis due to coronary atherosclerotic disease becomes the major locus of resistance to coronary blood flow, there is a decline in perfusion pressure distal to the stenosis. This results in ischemia when the normal mechanism for autoregulating coronary flow (i.c., coronary arteriolar vasodilatation) is no longer adequate to maintain flow.     

Pathophysiology of sickle cell disease

Sickle cell disease is caused by a mutation in the beta-globin chain of the haemoglobin molecule. Sickle haemoglobin, the result of this mutation, has the singular property of polymerizing when deoxygenated. Exactly how normal tissue perfusion is interrupted by abnormal sickle cells is complex and poorly understood. Despite genetic identity at the site of the sickle haemoglobin mutation, all patients with sickle cell anaemia are not affected equally by this disease. Secondary genetic determinants and acquired erythrocyte and vascular damage are likely to be central components of the pathophysiology of sickle cell anaemia.     

Pathophysiology of interstitial lung disease

Chronic interstitial lung disease (ILD) groups a number of diseases with the common feature of radiological pulmonary infiltration, typical functional syndrome, and diffuse involvement of the deep pulmonary parenchyma identified histologically. Correlations between histological and radiological findings have enabled progress in both fields, leading to better interpretation of the radiological findings and optimizing the etiological diagnosis. Besides the signs themselves, their distribution in relation to the normal lung structures is highly contributive. Function tests can be used to quantify the impact on the respiratory system and assess the effect of treatment. Evidence-based criteria will progressively replace the consensual criteria enabling more effective evaluation of treatment in difficult pathological conditions such as idiopathic pulmonary fibrosis.     

Pathophysiology of coronary artery disease

During the past decade, our understanding of the pathophysiology of coronary artery disease (CAD) has undergone a remarkable evolution. We review here how these advances have altered our concepts of and clinical approaches to both the chronic and acute phases of CAD. Previously considered a cholesterol storage disease, we currently view atherosclerosis as an inflammatory disorder. The appreciation of arterial remodeling (compensatory enlargement) has expanded attention beyond stenoses evident by angiography to encompass the biology of nonstenotic plaques. Revascularization effectively relieves ischemia, but we now recognize the need to attend to nonobstructive lesions as well. Aggressive management of modifiable risk factors reduces cardiovascular events and should accompany appropriate revascularization. We now recognize that disruption of plaques that may not produce critical stenoses causes many acute coronary syndromes (ACS). The disrupted plaque represents a "solid-state" stimulus to thrombosis. Alterations in circulating prothrombotic or antifibrinolytic mediators in the "fluid phase" of the blood can also predispose toward ACS. Recent results have established the multiplicity of "high-risk" plaques and the widespread nature of inflammation in patients prone to develop ACS. These findings challenge our traditional view of coronary atherosclerosis as a segmental or localized disease. Thus, treatment of ACS should involve 2 overlapping phases: first, addressing the culprit lesion, and second, aiming at rapid "stabilization" of other plaques that may produce recurrent events. The concept of "interventional cardiology" must expand beyond mechanical revascularization to embrace preventive interventions that forestall future events.     

Pathophysiology of myeloma bone disease

Multiple myeloma is a tumor of terminally differentiated plasma cells that home to and expand in the bone marrow. It is the second most common hematologic malignancy, with approximately 16,000 new cases per year, and accounts for an estimated 11,000 deaths in the USA. It is the most common cancer to metastasize to bone, with up to 90% of patients developing bone lesions. The bone lesions are purely osteolytic in nature, and up to 60% of patients develop a pathologic fracture over the course of their disease. Bone disease is a hallmark of multiple myeloma, and the bone disease differs from other bone metastasis caused by other tumors. Although both myeloma and other osteolytic metastasis induce increased osteoclastic bone resorption, in contrast to other tumors, osteoblast activity in myeloma is either severely decreased or absent. The basis for this severe imbalance between increased osteoclastic bone resorption and decreased bone formation resulting from suppressed osteoblastic activity has been a topic of extensive investigation during the last several years. The clinical consequences of this extensive accelerated and imbalanced bone destruction process include bone pain, pathologic fractures, hypercalcemia and spinal cord compression syndromes, which can be devastating for patients and significantly impact overall quality of life and expected survival. In this chapter, we will discuss the pathophysiology underlying bone disease in myeloma. This results from the uncoupling of bone remodeling and is characterized by markedly increased activity of osteoclasts and profound decreased activity of osteoblasts. In addition, we also review the emerging data on novel targeted therapies aimed at ameliorating myeloma bone disease.     

Pathophysiology of gastro-oesophageal reflux disease

Gastro-oesophageal reflux disease (GERD), defined as symptoms or mucosal damage caused by reflux of gastric contents into the esophageal body, is a multifactorial disorder. Malfunctioning of the anti-reflux barrier at the esophagogastric junction, consisting of the right diaphragmatic crus and the lower esophageal sphincter (LES), is the pivotal abnormality. Other factors such as impaired esophageal clearance, decreased resistance of the esophageal mucosa and delayed gastric emptying, may contribute.     

Pathophysiology of gastroesophageal reflux disease

The pathophysiology of gastroesophageal reflux disease remains incompletely understood. Its hallmark symptom is "heartburn" and, on the basis of endoscopy, those with heartburn are subdivided into nonerosive reflux disease and erosive esophagitis. Although subjects with nonerosive reflux disease have no gross damage on endoscopy, a characteristic histopathologic feature of this disease is present on endoscopic biopsy. This lesion is known as "dilated intercellular spaces," a finding present within squamous epithelium. This report details how acid in contact with a damaged esophageal epithelium leads to heartburn and to the progression of nonerosive reflux disease to erosive esophagitis. It also addresses the fact that esophageal pH monitoring may be normal in a significant number of subjects with heartburn, particularly with nonerosive reflux disease, and details how this observation suggests that in addition to defects in the antireflux barrier, for example, transient lower esophageal sphincter relaxations and low lower esophageal sphincter pressure, defects in tissue resistance created by contact with ingested products may also be etiologic in some subjects with gastroesophageal reflux disease.