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Basic Cytogenetics and the Role of Genetics in Cancer Development

Introduction This chapter will summarize the knowledge acquired on conventional cancer cytogenetics in the second half of the last century and introduces additional applications of fluorescent in situ hybridization (FISH) available for the study of cancer development and evolution. Other indications of these techniques applied on cytology samples are also described in Chapter 37 . Historical Background As suspected by von Hansemann more than a century…

The Cell: Basic Structure and Function, and Molecular Basis of Neoplasia

Basic Structure and Function of Mammalian Cells Overview Cells are the basic structural and functional units of all living organisms. Estimates about the total cell count of a human body vary widely, a number as large as 10 14 has been proposed. Although the basic components of all cells are very similar, the differentiation of cells results in a wide variation of cellular morphology and function.…

The Pericardium and its Diseases

The Pericardium and its Diseases The pericardium is a fibrous, relatively avascular tissue surrounding the heart which connects the heart to the sternum, diaphragm, and posteriorly to the anterior mediastinum. It consists of two layers: (1) the inner serous or visceral pericardium, also known as the epicardium; and (2) the outer fibrous parietal pericardium. The parietal pericardium consists of a fibrous sac that is less than…

Venous and Arterial Thrombosis

Introduction The pathogenesis of venous and arterial thrombosis is broad and at times disparate. Virchow originally described venous thrombosis under low flow (shear) with red clots, occurring around and propagating through venous valves, and consisting of red cells and fibrin strands. Arterial thrombosis occurs under high shear stress in large (carotids, coronary, femoral arteries) and small vessels and initially consists of platelets and leukocytes with few…

Blood Pressure Regulation and Pathology

Acknowledgments Quoted studies by the author were funded through grants from the Canadian Institutes of Health Research, the Heart and Stroke Foundation of Canada, the Kidney Foundation of Canada/Pfizer, and the Juvenile Diabetes Research Foundation. Introduction Elevated blood pressure, also known as hypertension, affects ∼30% of the adult population in both developed and developing countries and is a major cause of morbidity and mortality. Hypertension is…

Genetic Diseases of the Aorta (Including Aneurysms)

The Normal Aorta: Histology and Function The aorta is the largest artery, by caliber, in the human body. It is the conduit from the heart that extends from the thoracic cavity to the pelvic area where it bifurcates to create the iliac arteries. In adults, this vessel can measure around 490 cm in length. This elastic artery is important in absorbing the systolic bolus of blood…

Pathophysiology of Atherosclerosis

Introduction Credited to Felix Marchand in a 1904 publication, the name atherosclerosis roughly translates as ‘hardened gruel,’ This colorful term, reminiscent of other culinary metaphors in pathology, underlies many of the most feared and lethal conditions in medicine. Atherosclerosis is primarily an arterial disorder, classically characterized by lipid deposition in the vessel intima, and associated with inflammation, scarring, and calcification. Eventually these lesions cause luminal stenosis…

Diseases of Medium-Sized and Small Vessels

Introduction Vascular diseases extract a large toll on the human population, both in terms of mortality and quality of life. Vascular disease is in fact the leading cause of death in developed countries. Numerous pathologic conditions alter the structure and/or function of blood vessels. This chapter will cover the mechanisms of common disorders affecting medium-sized and small blood vessels, which are not discussed elsewhere in this…

Vasculogenesis and Angiogenesis

Introduction In light of the premise of angiogenesis as an organizing principle, it is not surprising that drugs that have been developed to modulate angiogenesis can be effective to treat apparently dissimilar conditions. For example, a blinding disease like wet age-related macular degeneration that affects primarily older individuals appears to have little in common with colorectal or lung cancer, yet these diseases may be treated using…

Calcific and Degenerative Heart Valve Disease

Introduction The collective global impact of the spectrum of valvular heart diseases is a serious but under-recognized health problem. In the developed and rapidly developing regions of the world, calcific and degenerative valve diseases are the most prevalent valvular abnormalities necessitating surgical intervention. Since these conditions occur progressively with age and lifespan is increasing in these areas, the number of new cases is projected to rise…

Molecular Pathobiology of Myocarditis

Introduction In the 1995 World Health Organization (WHO) Definition of Cardiomyopathies , myocarditis (also called inflammatory cardiomyopathy), is defined as an ‘inflammatory disease of the myocardium associated with cardiac dysfunction’ and is listed among ‘specific cardiomyopathies.’ Myocarditis is diagnosed in vivo on endomyocardial biopsy (EMB) by established histological, immunological, and immunohistochemical criteria, and molecular testing on EMB specimens is recommended to identify viral etiology. Infectious, autoimmune, and…

Cellular and Molecular Pathobiology of the Cardiac Conduction System

Overview of the Cardiac Conduction System The cardiac conduction system is a network of specialized cells responsible for the initiation and co-ordination of the heartbeat. Relative to the myocytes responsible for regulating cardiac contraction in a normal heart (~1 × 10 9 ), the cells that make up the cardiac conduction system are relatively few in number, but are essential for cardiac electrical signaling and normal…

Pathophysiology of Cardiomyopathies

Introduction Cardiomyocytes, the contractile cells of the heart, exist in a complex environment comprised of endothelial cells, vascular smooth muscle, fibroblasts, and immune cells. The components that form the extracellular matrix provide the structural framework and include protein-rich gap junctions that coordinate the contraction of individual myocytes to the extracellular matrix. Intracellularly, the myocytes are comprised of repeating units of sarcomeres that form the contractile units.…

Ischemic Heart Disease and its Consequences

Introduction Worldwide, cardiovascular disease, including cardiac disease, vascular diseases of the brain and kidney, and peripheral artery disease, is on the rise and continues to be the leading cause of morbidity and mortality in both men and women. Despite numerous advances in healthcare practices, it is estimated that 83.6 million American adults (about one in three) have one or more types of cardiovascular disease and that…

The Pathophysiology of Cardiac Hypertrophy and Heart Failure

Introduction Heart disease is a common global cause of morbidity and mortality. In the US alone, an estimated 83 million individuals carry the diagnosis and 1 in every 3 deaths are believed due to heart disease. More than 75% of patients have hypertension-related heart disease with associated cardiac enlargement. At the cellular level, chronic hypertension results in physiologic and pathological changes that culminate in adaptive changes…

Cardiac Atrophy and Remodeling

Overview of Atrophic Cardiac Remodeling Cardiac remodeling encompasses the many biochemical and molecular adaptations that the heart initiates in response to altered demand ( Figure 3.1 ). Atrophic remodeling occurs in response to ventricular or hemodynamic unloading caused by such stimuli as placement of an LVAD, surgical correction of cardiac valvular disease, bariatric surgery or pharmacological intervention in patients with hypertension. Upon unloading, the myocardium decreases…

Cardiac Metabolism in Health and Disease

Introduction Metabolism comes from the Greek word meaning ‘change,’ referring to the transformation of potential energy stored in circulating substrates such as glucose and fatty acids to adenosine triphosphate (ATP), thereby driving cardiac contraction and relaxation. Early workers delineated carbohydrate and fatty acids as two of the most important myocardial fuels. In 1914 Lovatt Evans found that about one-third of the dog heart’s energy was supplied…

Molecular Basis of Cardiac Development

Acknowledgments We would first like to apologize to the many authors whose studies were excluded due to space constraints. We would like to thank Dr. Andrea Portbury and Chelsea Cyr for critical reading of the manuscript. The Heart Fields and Heart Tube Formation The heart begins simply as a bilateral field within the lateral plate mesoderm ( Figure 1.1 , Table 1.1 ). As the early…

Forensic aspects of cardiovascular pathology

Open full size image Investigative information Investigation of sudden cardiac death (SCD), like all other sudden, unexpected, or unnatural death, relies heavily on a thorough and comprehensive investigation of the circumstances surrounding death, including a scene investigation, interview with family and friends regarding family history and social history, collection of relevant medical history from a treating physician, and review of the medical records. Interviews with friends…

Basic pathobiology of cell-based therapies and cardiac regenerative medicine

Central concept figure: evolution of cell therapy for myocardial repair and regeneration Introduction The late 1990s and early 2000s was a time period when major advances in stem cell biology were occurring . In this milieu, the concept of cell-based therapy to regenerate the damaged heart gained momentum . The need for definitive restorative therapy of the heart was compelling given the growing population of patients…