This document discusses cardiac biomarkers and energy metabolism in the heart. It begins by outlining the metabolic demands of the heart and how it meets most of its ATP needs through fatty acid oxidation. The major substrates that fuel heart contraction - fatty acids, carbohydrates, ketone bodies, and lactate - are described. Biomarkers of cardiac injury like cardiac troponins, CK-MB, myoglobin, and BNP are introduced. The timing and specificity of various biomarkers in detecting acute myocardial infarction is summarized. Finally, changes in heart metabolism during ischemia and the failing heart state are briefly outlined.
This document provides an overview of how different congenital heart diseases appear on chest x-rays. It describes the typical enlargements seen in different cardiac chambers and pulmonary vasculature for various conditions. For example, it notes that the right atrium is commonly enlarged in Ebstein's anomaly and atrial septal defects, while the left atrium may be enlarged in ventricular septal defects or patent ductus arteriosus. The document also discusses abnormalities in heart shape, such as a "boot"-shaped silhouette in tetralogy of Fallot. Overall, it serves as a guide for interpreting chest x-ray findings in the context of congenital heart disease.
This document discusses myocardial energetics, which refers to the energy produced and used by cardiomyocytes to power heart contraction and relaxation. The heart relies primarily on aerobic metabolism of fuels like fatty acids and glucose to generate ATP for this work. In healthy hearts, fatty acid oxidation provides most ATP, while glucose becomes more important in ischemia when oxygen is limited. Metabolic changes also occur in heart failure, like reduced fatty acid oxidation and mitochondrial dysfunction. Imaging techniques can examine metabolism by tracking fuels like glucose and fatty acids. Pharmacological treatments aim to improve metabolism, for example by enhancing glucose use over fatty acids.
This document discusses endomyocardial biopsy, an invasive procedure used to obtain heart muscle samples for histological examination to diagnose heart muscle disease. It provides a brief history of endomyocardial biopsy, describing early studies in the 1950s-1960s and the development of specialized biopsy catheters. The document outlines the current techniques for endomyocardial biopsy via the femoral, jugular, and subclavian veins. Potential complications are noted to be 3% for access site issues, 3% for biopsy related, and 1% each for arrhythmias and conduction abnormalities.
Coronary artery calcium predicts worse patient outcomes and is a challenge for stent placement. Lithotripsy uses sonic pressure waves to disrupt calcium and soften vessels, allowing improved stent expansion. Studies show lithotripsy modifies calcium safely with low risk of complications. It can treat calcium more effectively than atherectomy by impacting deeper, circumferential calcium and navigating tortuous anatomy while keeping wires in place. Lithotripsy may help improve outcomes for heavily calcified lesions.
This document discusses the no-reflow phenomenon, which occurs when restoration of coronary artery patency after procedures like primary percutaneous coronary intervention (PCI) does not translate to improved tissue perfusion. No-reflow occurs in 30% of patients after reperfusion for acute myocardial infarction and is associated with worse outcomes. It is caused by microvascular obstruction from distal embolization, ischemic injury, reperfusion injury, and individual patient susceptibility. Methods to diagnose no-reflow include angiography, coronary Doppler, cardiac MRI, and myocardial contrast echocardiography. Prevention strategies target reducing ischemic time, microvascular spasm, and distal embolization through early reperfusion, pharmacological agents, and ischemic conditioning techniques.
This document summarizes key concepts relating to cell injury, adaptation, and death. It discusses how cells respond to stress through reversible or irreversible injury, adaptation, or death. It also describes various types of cellular adaptation like hypertrophy, hyperplasia, atrophy, and metaplasia that cells undergo in response to stress. Additionally, it covers the mechanisms and morphological changes associated with different types of cell injury like necrosis and apoptosis.
This document provides an overview of Ebstein's anomaly, a congenital heart defect where the tricuspid valve is displaced downward into the right ventricle. It discusses the history, anatomy, pathophysiology, clinical presentation, diagnosis using echocardiography, associated abnormalities, and surgical management. Surgical techniques include biventricular repair to reconstruct the tricuspid valve, single ventricle palliation with right ventricle exclusion, and cardiac transplantation for the most severe cases with significant biventricular dysfunction.
This document discusses primary cardiac tumors, including their presentation, diagnosis, and types. It covers the following key points:
- The majority (75%) of primary cardiac tumors are benign neoplasms. Myxomas are the most common benign tumor, usually originating in the left atrium.
- Clinical presentation varies depending on tumor location and can include embolic phenomena, cardiac manifestations like obstruction, or symptoms of metastatic disease. Echocardiography is the primary diagnostic tool.
- Other common benign primary tumors include papillary fibroelastomas (found on heart valves) and lipomas. Rhabdomyomas are most often seen in children with tuberous sclerosis and can cause arrhythmias
This document provides an overview of how different congenital heart diseases appear on chest x-rays. It describes the typical enlargements seen in different cardiac chambers and pulmonary vasculature for various conditions. For example, it notes that the right atrium is commonly enlarged in Ebstein's anomaly and atrial septal defects, while the left atrium may be enlarged in ventricular septal defects or patent ductus arteriosus. The document also discusses abnormalities in heart shape, such as a "boot"-shaped silhouette in tetralogy of Fallot. Overall, it serves as a guide for interpreting chest x-ray findings in the context of congenital heart disease.
This document discusses myocardial energetics, which refers to the energy produced and used by cardiomyocytes to power heart contraction and relaxation. The heart relies primarily on aerobic metabolism of fuels like fatty acids and glucose to generate ATP for this work. In healthy hearts, fatty acid oxidation provides most ATP, while glucose becomes more important in ischemia when oxygen is limited. Metabolic changes also occur in heart failure, like reduced fatty acid oxidation and mitochondrial dysfunction. Imaging techniques can examine metabolism by tracking fuels like glucose and fatty acids. Pharmacological treatments aim to improve metabolism, for example by enhancing glucose use over fatty acids.
This document discusses endomyocardial biopsy, an invasive procedure used to obtain heart muscle samples for histological examination to diagnose heart muscle disease. It provides a brief history of endomyocardial biopsy, describing early studies in the 1950s-1960s and the development of specialized biopsy catheters. The document outlines the current techniques for endomyocardial biopsy via the femoral, jugular, and subclavian veins. Potential complications are noted to be 3% for access site issues, 3% for biopsy related, and 1% each for arrhythmias and conduction abnormalities.
Coronary artery calcium predicts worse patient outcomes and is a challenge for stent placement. Lithotripsy uses sonic pressure waves to disrupt calcium and soften vessels, allowing improved stent expansion. Studies show lithotripsy modifies calcium safely with low risk of complications. It can treat calcium more effectively than atherectomy by impacting deeper, circumferential calcium and navigating tortuous anatomy while keeping wires in place. Lithotripsy may help improve outcomes for heavily calcified lesions.
This document discusses the no-reflow phenomenon, which occurs when restoration of coronary artery patency after procedures like primary percutaneous coronary intervention (PCI) does not translate to improved tissue perfusion. No-reflow occurs in 30% of patients after reperfusion for acute myocardial infarction and is associated with worse outcomes. It is caused by microvascular obstruction from distal embolization, ischemic injury, reperfusion injury, and individual patient susceptibility. Methods to diagnose no-reflow include angiography, coronary Doppler, cardiac MRI, and myocardial contrast echocardiography. Prevention strategies target reducing ischemic time, microvascular spasm, and distal embolization through early reperfusion, pharmacological agents, and ischemic conditioning techniques.
This document summarizes key concepts relating to cell injury, adaptation, and death. It discusses how cells respond to stress through reversible or irreversible injury, adaptation, or death. It also describes various types of cellular adaptation like hypertrophy, hyperplasia, atrophy, and metaplasia that cells undergo in response to stress. Additionally, it covers the mechanisms and morphological changes associated with different types of cell injury like necrosis and apoptosis.
This document provides an overview of Ebstein's anomaly, a congenital heart defect where the tricuspid valve is displaced downward into the right ventricle. It discusses the history, anatomy, pathophysiology, clinical presentation, diagnosis using echocardiography, associated abnormalities, and surgical management. Surgical techniques include biventricular repair to reconstruct the tricuspid valve, single ventricle palliation with right ventricle exclusion, and cardiac transplantation for the most severe cases with significant biventricular dysfunction.
This document discusses primary cardiac tumors, including their presentation, diagnosis, and types. It covers the following key points:
- The majority (75%) of primary cardiac tumors are benign neoplasms. Myxomas are the most common benign tumor, usually originating in the left atrium.
- Clinical presentation varies depending on tumor location and can include embolic phenomena, cardiac manifestations like obstruction, or symptoms of metastatic disease. Echocardiography is the primary diagnostic tool.
- Other common benign primary tumors include papillary fibroelastomas (found on heart valves) and lipomas. Rhabdomyomas are most often seen in children with tuberous sclerosis and can cause arrhythmias
- Cardiac tumors are rare, with most cardiac masses representing thrombi or vegetations. Primary cardiac tumors are more often benign, with myxoma being the most common benign tumor found in the left atrium attached to the fossa ovalis. In children, rhabdomyomas and fibromas are the most typical primary benign tumors. Secondary cardiac tumors are more prevalent, spreading from other primary cancers. Noninvasive diagnosis relies on tumor location, age, imaging characteristics, and histology likelihood.
HCM – Presentation, Hemodynamics and InterventionAnkur Gupta
This document describes a case of a 50-year-old female presenting with symptoms of breathlessness, angina, and presyncope. Echocardiography revealed asymmetric septal hypertrophy and systolic anterior motion of the mitral valve, consistent with hypertrophic obstructive cardiomyopathy (HOCM). The document then provides detailed background information on HOCM, including definitions, pathophysiology, clinical presentation, diagnostic testing, and treatment options such as beta-blockers, septal ablation, and disqualification from competitive sports in severe cases.
1. Aortic arch anomalies result from errors in the embryological development of the branchial arches and the regression of vascular structures. They account for 15-20% of all congenital cardiovascular diseases.
2. Strong associations have been found between arch anomalies and chromosomal/genetic abnormalities like deletions on chromosome 22q11.
3. Arch anomalies can cause symptoms from airway or esophageal compression or be incidental findings on imaging. The most common types are double aortic arch, right aortic arch with aberrant left subclavian artery, and right aortic arch with retroesophageal diverticulum of Kommerell.
This document provides information on several types of congenital and rheumatic heart disease, as well as surgical correction of cardiovascular lesions. It discusses congenital heart defects such as atrial and ventricular septal defects, tetralogy of Fallot, coarctation of the aorta, and patent ductus arteriosus. For each condition, it describes the etiology, clinical features, investigations, and management approaches. The document emphasizes that while many congenital heart defects used to be fatal in childhood, surgery can now correct or partially repair many conditions, allowing survival into adulthood.
1. Myxomas are the most common primary cardiac tumor, usually occurring in the left atrium and presenting with signs and symptoms similar to mitral valve disease like dyspnea and murmurs.
2. Other common benign tumors include rhabdomyomas in children and lipomas, while sarcomas are the most common malignant cardiac tumors in adults presenting with rapid progression.
3. Metastatic tumors to the heart are more common than primary cardiac tumors, usually from melanoma and lung/breast cancers through hematogenous spread.
There are 9 main classes of cancer: carcinomas, neuroectodermal tumors, sarcomas, hemolymphoid tumors, germ cell tumors, blastemal tumors, embryonal vestigal remnants tumors, uncertain histogenesis tumors, and undifferentiated tumors. Carcinomas are the most common type, arising from epithelial cells. Sarcomas arise from mesenchymal cells and grow more rapidly than carcinomas. Neuroectodermal tumors include tumors of neural, neuroendocrine, and primitive neuroectodermal origin. Hemolymphoid malignancies include lymphomas and leukemias. Other classes are defined by their origin from germ cells, embryonic rests, vestigial remnants
This document provides guidelines for managing adult congenital heart disease (ACHD). It discusses how ACHD involves a range of cardiac abnormalities present at birth, excluding inherited disorders. When ACHD involves acquired disease, the focus is on differences from that disease due to anatomy, other lesions, or patient age. Survival of severe CHD to adulthood is now over 90%, but ACHD patients are heterogeneous in anatomy, physiology, and surgical history. The document presents a classification system to comprehensively assess ACHD severity based on anatomy and physiology.
This document provides information on Ebstein's anomaly, including its anatomy, embryology, clinical presentation, diagnosis, and natural history. Some key points:
- Ebstein's anomaly is a congenital defect involving downward displacement of the tricuspid valve into the right ventricle. This can cause dilation of the right atrium and dysfunction of the right ventricle.
- Clinical presentation varies from neonatal congestive heart failure to later cyanosis, arrhythmias, and right heart failure in adults. Associated defects are common.
- Diagnosis is made through echocardiogram demonstrating displacement of the tricuspid valve leaflets. Other tests like ECG, chest x-ray, and
The heart consumes large amounts of ATP daily through oxidative phosphorylation using fatty acids, lactate, glucose, and triglycerides as fuel sources. During ischemia, fatty acid oxidation and lactate formation increase while ATP production decreases. Biomarkers like troponins, CK-MB, and myoglobin indicate cardiac injury, with troponins being highly specific and predictive of outcomes. Troponin levels remain elevated for over a week, enabling detection of minor necrosis. C-reactive protein also predicts cardiovascular risk.
Intravascular lithotripsy (ivl) for peripheral arterial diseaseRamachandra Barik
There are a number of observations that suggest IVL produces
compliance changes in the vessel wall:Effacement of calcified stenoses with lithotripsy at low pressure with no change in angioplasty balloon pressure •Changes in echotexture on Duplex Ultrasound•Changes in appearances on Optical Coherence Tomography
Primary cardiac tumors are rare but can involve the heart directly or through metastasis. Benign tumors like myxomas are the most common primary cardiac tumors and often present with nonspecific symptoms of obstruction, embolism, or constitutional effects. Myxomas typically occur in the left atrium of middle-aged women and can be part of Carney syndrome, characterized by extracardiac tumors and skin pigmentation. Echocardiography is the primary diagnostic tool used to identify location and characteristics of a suspected cardiac tumor.
The document discusses atrial septal defects (ASDs), including indications for closure, procedural details, and echocardiographic assessment. Key points include:
- ASD closure is recommended in the presence of right-sided heart volume overload or symptoms. It prevents further deterioration and helps normalize heart size.
- Indications for closure include hemodynamically significant ASD, paradoxical embolism risk, and transient cyanosis. Contraindications include irreversible pulmonary hypertension.
- Echocardiography is used to assess defect size, rims, and shunt severity. Deficient rims, especially aortic and superior vena cava, increase erosion risk post-closure.
This document discusses cell injury and cell death. It notes that cells have a normal steady state of homeostasis but stress can force adaptation or injury. Cell injury can be reversible or irreversible, depending on the severity and duration of the stress. Irreversible injury leads to cell death. Mechanisms of injury include damage to membranes, respiration, protein synthesis, and DNA. Causes include hypoxia, free radicals, chemicals, infections, and physical or immunological stresses. Reversible injury disrupts mitochondria and ATP production, while irreversible injury severely damages membranes and organelles. The morphology of injury progresses from reversible changes like swelling to irreversible changes like membrane breaks and nuclear fragmentation. Types of cell death include apoptosis and various forms
This document discusses cardiac tumors. It begins by classifying cardiac tumors as neoplastic or non-neoplastic lesions and further classifying neoplastic lesions as benign or malignant tumors. The document then discusses the incidence, clinical manifestations, diagnostic evaluations, and approaches to different types of cardiac masses and benign tumors specifically, covering myxomas, lipomas, papillary fibroelastomas, and rhabdomyomas.
This document discusses techniques for localizing the site of origin of ventricular tachycardia based on electrocardiogram characteristics. It describes that right ventricular outflow tract tachycardias typically present with left bundle branch block morphology while left ventricular sites may present with either right or left bundle branch block depending on exit site. Specific leads are discussed that can provide clues about anterior vs posterior, septal vs free wall origin within the outflow tracts. Other areas like fascicles, papillary muscles and mitral/tricuspid annuli are also summarized.
Natural history and treatment of aortic stenosisKunal Mahajan
This document discusses the natural history and treatment of aortic stenosis. It defines the severity classifications based on aortic jet velocity, mean gradient, and valve area. Symptoms rarely occur with severe aortic stenosis if left ventricular function is normal. The document reviews progression rates in asymptomatic patients and risk factors for more rapid progression. Exercise testing may help identify higher risk asymptomatic patients but is not routinely recommended. Biomarkers like BNP levels can also predict outcomes. The prognosis is poor once patients become symptomatic, so surgical intervention is recommended for symptomatic severe aortic stenosis.
This document discusses aortic aneurysms, including their anatomy, physiology, risk factors, diagnosis, and management. It provides details on:
1) The layers of the aortic wall and how they give the aorta elasticity and strength.
2) Factors that cause the aortic wall to stiffen with age like increases in collagen and calcification of elastic fibers.
3) Definitions of aortic aneurysm and classifications based on location and shape. Thoracic aortic aneurysms involve the ascending aorta while abdominal aortic aneurysms are infrarenal.
4) Screening recommendations, diagnosis using imaging like ultrasound, CT and echocardiography, and considerations for open surgical repair
Left ventricular outflow tract obstructions are stenotic lesions in the left ventricular outflow tract that obstruct blood flow. They impose increased pressure load on the left ventricle and can lead to ventricular hypertrophy and failure if left untreated. Clinical manifestations include acute hemodynamic deterioration, shock, and end organ injury in newborns. Long term, patients are at risk for shortness of breath, chest pain, and fainting. Treatment involves surgical intervention such as balloon valvuloplasty or valve replacement to restore blood flow. All patients with LVOTO are at lifetime risk for infective endocarditis.
This document provides an overview of carbohydrate metabolism and associated disorders. It discusses the regulation of glycolysis and phosphofructokinase, the significance of glycolysis in meeting energy demands, and disorders associated with deficiencies in glycolysis enzymes. It also covers topics like the Rapoport-Leubering cycle, effects of altitude on hemoglobin, and the importance of gluconeogenesis during fasting.
Fatty Acids are Aliphatic carboxylic acids and each animal species will have characteristic pattern of fatty acid composition. Thus, human body fat contains 50% oleic acid, 25% palmitic acid, 10% linoleic acid and 5% stearic acid.
- Cardiac tumors are rare, with most cardiac masses representing thrombi or vegetations. Primary cardiac tumors are more often benign, with myxoma being the most common benign tumor found in the left atrium attached to the fossa ovalis. In children, rhabdomyomas and fibromas are the most typical primary benign tumors. Secondary cardiac tumors are more prevalent, spreading from other primary cancers. Noninvasive diagnosis relies on tumor location, age, imaging characteristics, and histology likelihood.
HCM – Presentation, Hemodynamics and InterventionAnkur Gupta
This document describes a case of a 50-year-old female presenting with symptoms of breathlessness, angina, and presyncope. Echocardiography revealed asymmetric septal hypertrophy and systolic anterior motion of the mitral valve, consistent with hypertrophic obstructive cardiomyopathy (HOCM). The document then provides detailed background information on HOCM, including definitions, pathophysiology, clinical presentation, diagnostic testing, and treatment options such as beta-blockers, septal ablation, and disqualification from competitive sports in severe cases.
1. Aortic arch anomalies result from errors in the embryological development of the branchial arches and the regression of vascular structures. They account for 15-20% of all congenital cardiovascular diseases.
2. Strong associations have been found between arch anomalies and chromosomal/genetic abnormalities like deletions on chromosome 22q11.
3. Arch anomalies can cause symptoms from airway or esophageal compression or be incidental findings on imaging. The most common types are double aortic arch, right aortic arch with aberrant left subclavian artery, and right aortic arch with retroesophageal diverticulum of Kommerell.
This document provides information on several types of congenital and rheumatic heart disease, as well as surgical correction of cardiovascular lesions. It discusses congenital heart defects such as atrial and ventricular septal defects, tetralogy of Fallot, coarctation of the aorta, and patent ductus arteriosus. For each condition, it describes the etiology, clinical features, investigations, and management approaches. The document emphasizes that while many congenital heart defects used to be fatal in childhood, surgery can now correct or partially repair many conditions, allowing survival into adulthood.
1. Myxomas are the most common primary cardiac tumor, usually occurring in the left atrium and presenting with signs and symptoms similar to mitral valve disease like dyspnea and murmurs.
2. Other common benign tumors include rhabdomyomas in children and lipomas, while sarcomas are the most common malignant cardiac tumors in adults presenting with rapid progression.
3. Metastatic tumors to the heart are more common than primary cardiac tumors, usually from melanoma and lung/breast cancers through hematogenous spread.
There are 9 main classes of cancer: carcinomas, neuroectodermal tumors, sarcomas, hemolymphoid tumors, germ cell tumors, blastemal tumors, embryonal vestigal remnants tumors, uncertain histogenesis tumors, and undifferentiated tumors. Carcinomas are the most common type, arising from epithelial cells. Sarcomas arise from mesenchymal cells and grow more rapidly than carcinomas. Neuroectodermal tumors include tumors of neural, neuroendocrine, and primitive neuroectodermal origin. Hemolymphoid malignancies include lymphomas and leukemias. Other classes are defined by their origin from germ cells, embryonic rests, vestigial remnants
This document provides guidelines for managing adult congenital heart disease (ACHD). It discusses how ACHD involves a range of cardiac abnormalities present at birth, excluding inherited disorders. When ACHD involves acquired disease, the focus is on differences from that disease due to anatomy, other lesions, or patient age. Survival of severe CHD to adulthood is now over 90%, but ACHD patients are heterogeneous in anatomy, physiology, and surgical history. The document presents a classification system to comprehensively assess ACHD severity based on anatomy and physiology.
This document provides information on Ebstein's anomaly, including its anatomy, embryology, clinical presentation, diagnosis, and natural history. Some key points:
- Ebstein's anomaly is a congenital defect involving downward displacement of the tricuspid valve into the right ventricle. This can cause dilation of the right atrium and dysfunction of the right ventricle.
- Clinical presentation varies from neonatal congestive heart failure to later cyanosis, arrhythmias, and right heart failure in adults. Associated defects are common.
- Diagnosis is made through echocardiogram demonstrating displacement of the tricuspid valve leaflets. Other tests like ECG, chest x-ray, and
The heart consumes large amounts of ATP daily through oxidative phosphorylation using fatty acids, lactate, glucose, and triglycerides as fuel sources. During ischemia, fatty acid oxidation and lactate formation increase while ATP production decreases. Biomarkers like troponins, CK-MB, and myoglobin indicate cardiac injury, with troponins being highly specific and predictive of outcomes. Troponin levels remain elevated for over a week, enabling detection of minor necrosis. C-reactive protein also predicts cardiovascular risk.
Intravascular lithotripsy (ivl) for peripheral arterial diseaseRamachandra Barik
There are a number of observations that suggest IVL produces
compliance changes in the vessel wall:Effacement of calcified stenoses with lithotripsy at low pressure with no change in angioplasty balloon pressure •Changes in echotexture on Duplex Ultrasound•Changes in appearances on Optical Coherence Tomography
Primary cardiac tumors are rare but can involve the heart directly or through metastasis. Benign tumors like myxomas are the most common primary cardiac tumors and often present with nonspecific symptoms of obstruction, embolism, or constitutional effects. Myxomas typically occur in the left atrium of middle-aged women and can be part of Carney syndrome, characterized by extracardiac tumors and skin pigmentation. Echocardiography is the primary diagnostic tool used to identify location and characteristics of a suspected cardiac tumor.
The document discusses atrial septal defects (ASDs), including indications for closure, procedural details, and echocardiographic assessment. Key points include:
- ASD closure is recommended in the presence of right-sided heart volume overload or symptoms. It prevents further deterioration and helps normalize heart size.
- Indications for closure include hemodynamically significant ASD, paradoxical embolism risk, and transient cyanosis. Contraindications include irreversible pulmonary hypertension.
- Echocardiography is used to assess defect size, rims, and shunt severity. Deficient rims, especially aortic and superior vena cava, increase erosion risk post-closure.
This document discusses cell injury and cell death. It notes that cells have a normal steady state of homeostasis but stress can force adaptation or injury. Cell injury can be reversible or irreversible, depending on the severity and duration of the stress. Irreversible injury leads to cell death. Mechanisms of injury include damage to membranes, respiration, protein synthesis, and DNA. Causes include hypoxia, free radicals, chemicals, infections, and physical or immunological stresses. Reversible injury disrupts mitochondria and ATP production, while irreversible injury severely damages membranes and organelles. The morphology of injury progresses from reversible changes like swelling to irreversible changes like membrane breaks and nuclear fragmentation. Types of cell death include apoptosis and various forms
This document discusses cardiac tumors. It begins by classifying cardiac tumors as neoplastic or non-neoplastic lesions and further classifying neoplastic lesions as benign or malignant tumors. The document then discusses the incidence, clinical manifestations, diagnostic evaluations, and approaches to different types of cardiac masses and benign tumors specifically, covering myxomas, lipomas, papillary fibroelastomas, and rhabdomyomas.
This document discusses techniques for localizing the site of origin of ventricular tachycardia based on electrocardiogram characteristics. It describes that right ventricular outflow tract tachycardias typically present with left bundle branch block morphology while left ventricular sites may present with either right or left bundle branch block depending on exit site. Specific leads are discussed that can provide clues about anterior vs posterior, septal vs free wall origin within the outflow tracts. Other areas like fascicles, papillary muscles and mitral/tricuspid annuli are also summarized.
Natural history and treatment of aortic stenosisKunal Mahajan
This document discusses the natural history and treatment of aortic stenosis. It defines the severity classifications based on aortic jet velocity, mean gradient, and valve area. Symptoms rarely occur with severe aortic stenosis if left ventricular function is normal. The document reviews progression rates in asymptomatic patients and risk factors for more rapid progression. Exercise testing may help identify higher risk asymptomatic patients but is not routinely recommended. Biomarkers like BNP levels can also predict outcomes. The prognosis is poor once patients become symptomatic, so surgical intervention is recommended for symptomatic severe aortic stenosis.
This document discusses aortic aneurysms, including their anatomy, physiology, risk factors, diagnosis, and management. It provides details on:
1) The layers of the aortic wall and how they give the aorta elasticity and strength.
2) Factors that cause the aortic wall to stiffen with age like increases in collagen and calcification of elastic fibers.
3) Definitions of aortic aneurysm and classifications based on location and shape. Thoracic aortic aneurysms involve the ascending aorta while abdominal aortic aneurysms are infrarenal.
4) Screening recommendations, diagnosis using imaging like ultrasound, CT and echocardiography, and considerations for open surgical repair
Left ventricular outflow tract obstructions are stenotic lesions in the left ventricular outflow tract that obstruct blood flow. They impose increased pressure load on the left ventricle and can lead to ventricular hypertrophy and failure if left untreated. Clinical manifestations include acute hemodynamic deterioration, shock, and end organ injury in newborns. Long term, patients are at risk for shortness of breath, chest pain, and fainting. Treatment involves surgical intervention such as balloon valvuloplasty or valve replacement to restore blood flow. All patients with LVOTO are at lifetime risk for infective endocarditis.
This document provides an overview of carbohydrate metabolism and associated disorders. It discusses the regulation of glycolysis and phosphofructokinase, the significance of glycolysis in meeting energy demands, and disorders associated with deficiencies in glycolysis enzymes. It also covers topics like the Rapoport-Leubering cycle, effects of altitude on hemoglobin, and the importance of gluconeogenesis during fasting.
Fatty Acids are Aliphatic carboxylic acids and each animal species will have characteristic pattern of fatty acid composition. Thus, human body fat contains 50% oleic acid, 25% palmitic acid, 10% linoleic acid and 5% stearic acid.
This document discusses cellular respiration and the processes involved in breaking down glucose to generate energy in the form of ATP. It covers the key steps of glycolysis, which takes place in the cytoplasm, the Krebs cycle (also called the citric acid cycle), which occurs in the mitochondria, and the electron transport chain. The document outlines the learning objectives, provides an overview of cellular respiration, and describes in detail each step in breaking down glucose, including the generation of NADH and FADH2 to carry energy to the electron transport chain for oxidative phosphorylation to produce ATP.
1. Lipid metabolism involves the oxidation of fatty acids and cholesterol biosynthesis. Fatty acids undergo beta-oxidation to produce acetyl-CoA for the citric acid cycle. Cholesterol is synthesized from acetyl-CoA in the cytosol.
2. Beta-oxidation of fatty acids occurs through four steps in the mitochondria to ultimately produce acetyl-CoA. Cholesterol synthesis involves multiple enzyme-catalyzed steps beginning with the formation of mevalonate from acetyl-CoA.
3. Lipid transport involves chylomicrons, VLDL, IDL, LDL, and HDL. Diseases can arise from defects in lipid metabolism pathways or lipid transport systems. Blood lipid levels
Lipid metabolism involves the oxidation of fatty acids to produce energy. There are three main types of fatty acid oxidation: beta, alpha, and omega. Beta-oxidation occurs in the mitochondria and breaks down fatty acids into acetyl-CoA via a four-step process. Cholesterol is synthesized from acetyl-CoA in the liver through a series of reactions. Ketone bodies such as acetoacetate and beta-hydroxybutyrate are produced from acetyl-CoA in the liver during periods of low glucose and provide energy for other tissues. Lipoproteins such as chylomicrons, VLDL, LDL, and HDL are involved in transporting lipids between tissues.
The document discusses glycolysis and the citric acid cycle. Glycolysis involves 10 steps that break down glucose and generate a small amount of ATP without oxygen. The citric acid cycle is a series of chemical reactions in the mitochondria that further oxidizes pyruvate from glycolysis to extract more chemical energy. It involves 8 steps that produce carbon dioxide, NADH, and FADH2 to fuel the electron transport chain for oxidative phosphorylation to generate large amounts of ATP. Both pathways are tightly regulated and provide precursors for other biological processes.
The TCA cycle, also known as the Krebs cycle or citric acid cycle, is the final common pathway for the oxidation of carbohydrates, fats, and proteins. It generates energy through the oxidation of acetyl-CoA derived from these nutrients and provides precursors for amino acid, nucleotide, and lipid synthesis. The cycle takes place in the matrix of mitochondria and involves 8 steps that completely oxidize acetyl-CoA to produce carbon dioxide and water while generating reduced cofactors NADH and FADH2. These cofactors then transfer electrons to the electron transport chain to facilitate ATP production through oxidative phosphorylation.
Carbohydrate metabolism & Interconnection of Metabolism with Respiratory chainDr.Subir Kumar
This document provides an overview of various topics related to metabolism including anabolism, catabolism, the purpose of metabolism, energy metabolism, the paradigm of metabolism, bioenergetics, energy phosphate compounds, ATP-ADP cycle, the role of ATP in bioenergetics, carbohydrate metabolism, intermediary metabolism of glucose, the glucose pool, glucose homeostasis, the glucostatic functions of the liver, the metabolic fates of glucose, types of metabolic reactions, glycolysis, the citric acid cycle, the respiratory chain, gluconeogenesis, the Cory cycle, the glucose-alanine cycle, the hexose monophosphate shunt, and their importance.
This document summarizes key aspects of metabolism integration. It discusses the major macronutrients and their roles in energy production and storage. The major metabolic pathways are described, including their junction points and regulatory enzymes. Specific pathways for glucose, fatty acids, and amino acids are explained. The roles of the liver in metabolic integration and regulation by hormones like insulin and glucagon are highlighted.
The document summarizes the three stages of catabolism:
1. Pyruvate is converted to acetyl-CoA in the mitochondria by the pyruvate dehydrogenase complex. This is the committed step to the citric acid cycle.
2. The pyruvate dehydrogenase complex contains three enzymes and requires five cofactors including thiamine pyrophosphate and Coenzyme A.
3. Acetyl-CoA then enters the citric acid cycle, which occurs in the mitochondrial matrix and fully oxidizes acetyl-CoA, producing carbon dioxide and reducing equivalents like NADH and FADH2.
The document discusses metabolism of macronutrients like carbohydrates, proteins and lipids. It describes major metabolic pathways like glycolysis, TCA cycle, oxidative phosphorylation. It discusses key regulatory points and fate of glucose, fatty acids and amino acids. It also discusses tissue-specific metabolism in brain, muscle, heart, kidney and liver. Finally, it summarizes changes in carbohydrate, lipid and amino acid metabolism during the fed-fast cycle.
The document discusses carbohydrate metabolism, specifically glucose metabolism and the pathways involved in glucose oxidation and storage. It covers the following key points:
1) Glycolysis and the citric acid cycle are the two major pathways for glucose oxidation and energy production. Glycolysis occurs in the cytoplasm and citric acid cycle in the mitochondria.
2) Glycolysis converts glucose to pyruvate, producing a small amount of energy. Pyruvate can then enter the citric acid cycle or be converted to lactate.
3) The citric acid cycle further oxidizes acetyl groups from pyruvate, producing more energy through the electron transport chain.
This document discusses the integration and compartmentalization of metabolism. It covers various metabolic pathways such as glycolysis, the citric acid cycle, fatty acid synthesis, and ketone body formation. It also summarizes the metabolic profiles of different tissues including muscle, liver, kidney, and adipose tissue. Key points covered include the primary fuels used by different tissues, metabolic fates of compounds like glucose-6-phosphate and pyruvate, and mitochondrial shuttles that transport metabolites between organelles.
Lipid metabolism involves the breakdown and storage of fats. Key processes include beta-oxidation of fatty acids in the mitochondria, ketogenesis in the liver during fasting or diabetes, and de novo synthesis of fatty acids like palmitic acid. Cholesterol is important for cell membranes and can be converted to bile acids, steroid hormones like estrogen and testosterone, and vitamin D. Disorders of lipid metabolism include hypercholesterolemia, atherosclerosis, fatty liver disease, and obesity.
Lipid metabolism involves the breakdown and storage of fats. Key processes include beta-oxidation of fatty acids in the mitochondria, ketogenesis in the liver during fasting or starvation, and de novo synthesis of fatty acids like palmitic acid. Cholesterol is important for cell membranes and can be converted to bile acids, steroid hormones like estrogen and testosterone, and vitamin D. Disorders of lipid metabolism include hypercholesterolemia, atherosclerosis, fatty liver disease, and obesity.
This document provides information on the digestion, absorption, and metabolism of lipids. It discusses how dietary lipids are broken down by lipases in the mouth, stomach, and small intestine. Pancreatic lipase plays a major role in digesting triglycerides into fatty acids and monoacylglycerides. These products are absorbed via micelles in the small intestine and resynthesized into triglycerides for transport to the liver and peripheral tissues. The document also outlines the pathways of beta-oxidation of fatty acids in mitochondria, ketogenesis in the liver from fatty acids, and utilization of ketone bodies by extrahepatic tissues.
Metabolism is the network of chemical reactions that take place in living cells. It performs four main functions: obtaining energy, converting nutrients into macromolecules, assembling macromolecules, and degrading macromolecules. Metabolic pathways can be catabolic, anabolic, or amphibolic. Glycolysis converts glucose into pyruvate, generating a small amount of ATP. Pyruvate then undergoes oxidative decarboxylation to form acetyl-CoA, the entry point into the citric acid cycle. Diseases can impair glycolysis through deficiencies in enzymes like pyruvate kinase or disorders that cause lactic acidosis.
This document provides information on various aspects of carbohydrate and energy metabolism, including the Krebs cycle, cellular respiration, glycolysis, gluconeogenesis, glycogen metabolism, the hexose monophosphate shunt, electron transport chain, and diabetes. It describes the key steps and functions of these metabolic pathways, emphasizing that they work together to break down glucose and other fuels to generate energy in the form of ATP through oxidative phosphorylation in the mitochondria. Diabetes results from deficiencies in insulin production or action that disrupt the normal regulation of blood glucose levels.
This document provides information on various aspects of carbohydrate and energy metabolism, including the Krebs cycle, cellular respiration, glycolysis, gluconeogenesis, glycogen metabolism, the hexose monophosphate shunt, electron transport chain, and hormonal regulation of blood glucose levels and diabetes mellitus. It describes the key steps and functions of these metabolic pathways, discusses their clinical significance, and explains how insulin and glucagon work to regulate blood glucose homeostasis and the complications that can arise from diabetes.
Similar to CVS cariac energy metabolism -.pptx (20)
The lymphatic system consists of lymph vessels, lymph nodes, spleen, thymus, tonsils, and other lymphoid tissues. The lymph vessels return interstitial fluid to the blood circulation and help protect the body from disease. Primary lymphoid organs like the bone marrow and thymus produce immune cells, while secondary organs like lymph nodes, spleen, and mucosa-associated lymphoid tissue house and transport lymphocytes throughout the body. Histologically, lymphoid tissues contain aggregates of lymphocytes and other immune cells organized into structures like follicles, cords, and sheaths that vary between organs.
The document provides details about the cardiovascular system histology. It begins with an introduction to the circulatory system and cardiovascular system. It then describes the layers of the heart - endocardium, myocardium and epicardium. Next, it discusses the types of blood vessels - arteries, which are divided into elastic arteries, muscular arteries and arterioles, and veins. It provides information on the layers of blood vessel walls - tunica intima, tunica media and tunica externa/adventitia. Finally, it describes the different types of capillaries - continuous, fenestrated and sinusoidal capillaries.
The cardiovascular system is the first major system to function in the embryo. The primordial heart and vascular system appear around the third week of development. The heart tube begins as paired endothelial strands that fuse to form a single tube. It develops layers and regions that will give rise to the adult heart structures. The heart begins beating around week 5 and blood circulation is established. A system of veins drains blood into the heart and these veins remodel extensively throughout development. Septa form between weeks 3-5 to partition the heart chambers and align blood flow properly.
Lipoproteins are complexes of protein and lipids that transport lipids in the bloodstream. There are four main types of lipoproteins: chylomicrons, very low-density lipoproteins (VLDL), low-density lipoproteins (LDL), and high-density lipoproteins (HDL). Each type has a specific function in lipid transport and metabolism. Chylomicrons transport dietary lipids from the intestine to other tissues, VLDL transports endogenous lipids from the liver, LDL delivers cholesterol to tissues, and HDL transports cholesterol from tissues back to the liver. The apolipoproteins associated with each lipoprotein complex help determine its structure and function in lipid transport and metabolism.
1. Platelets are formed in the bone marrow from megakaryocytes and play a key role in hemostasis, the process of blood clotting.
2. When a blood vessel is injured, platelets adhere to the damaged vessel wall and release chemicals that attract more platelets to form a platelet plug.
3. The coagulation cascade is activated, involving clotting factors produced in the liver. This leads to the formation of a fibrin mesh that strengthens the platelet plug and forms a blood clot to seal the damaged vessel.
Blood transports gases, nutrients, wastes, hormones, and defends against infection. It is composed of plasma and formed elements including red blood cells, white blood cells, and platelets. Red blood cells contain hemoglobin which transports oxygen and carbon dioxide. Hemoglobin is produced through erythropoiesis, regulated by erythropoietin, where stem cells in bone marrow mature into reticulocytes over 15 days then biconcave red blood cells. Red blood cells live for 120 days then are phagocytosed by the liver and spleen.
The document discusses white blood cells (WBCs), also known as leukocytes. It describes their key properties, including that they have nuclei, fight infections through phagocytosis and antibody/lymphocyte production, and are highly mobile. It classifies WBCs based on their granularity and nuclear morphology. The main types discussed are neutrophils, lymphocytes, monocytes, eosinophils, and basophils. It also covers the mechanisms and roles of phagocytosis, complement system, and lymphocytes.
The document describes the anatomy of the thorax. It is divided into three parts: the superior mediastinum, inferior mediastinum, and subdivisions of the inferior mediastinum. The superior mediastinum contains the thymus gland, veins, arteries including the aortic arch, and nerves such as the vagus and phrenic. The inferior mediastinum is further divided by the pericardial sac into the anterior, middle and posterior mediastinum. Key structures such as the trachea, esophagus, arteries and veins are described in detail in their locations within the mediastinum.
The document discusses the structure and function of blood vessels in the body. It describes the three main types of blood vessels - arteries, capillaries, and veins - and their roles in circulating blood. It also details the layers of blood vessel walls, types of blood vessels like arterioles and venules, and how capillaries form beds to supply tissues. Finally, it summarizes the pulmonary and systemic circuits, focusing on major arteries like those in the brain, neck, chest and their branching patterns.
The lymphatic system returns tissue fluid to the bloodstream and helps protect the body from disease. It consists of lymph vessels, lymph tissue in organs, and lymphatic organs. The lymph vessels collect excess tissue fluid and return it to the bloodstream, while also transporting fat and defending the body. Lymph flows through a series of vessels and nodes before emptying into veins in the neck. The nodes filter the lymph and activate the immune system. Blockages can cause swelling.
This document discusses the components and functions of blood. It notes that blood is composed of formed elements (blood cells) suspended in fluid plasma. The main cell types are red blood cells, which transport oxygen and carbon dioxide, and white blood cells, including neutrophils, lymphocytes, monocytes, eosinophils, and basophils, which fight infection. Platelets help the blood clot. Together, blood cells and plasma transport nutrients, waste, hormones, and other substances to tissues and regulate temperature, pH, electrolytes, and immunity.
Hemopoiesis is the process of blood cell formation in the bone marrow and other hematopoietic tissues. Mature blood cells have short lifespans and must be continuously replaced. The document discusses the stages of development of red blood cells, granulocytes, and other blood cell types from hematopoietic stem cells through progenitor and precursor cells with the influence of growth factors in the bone marrow microenvironment. It also describes the structure and cellular components of red bone marrow.
Cell Therapy Expansion and Challenges in Autoimmune DiseaseHealth Advances
There is increasing confidence that cell therapies will soon play a role in the treatment of autoimmune disorders, but the extent of this impact remains to be seen. Early readouts on autologous CAR-Ts in lupus are encouraging, but manufacturing and cost limitations are likely to restrict access to highly refractory patients. Allogeneic CAR-Ts have the potential to broaden access to earlier lines of treatment due to their inherent cost benefits, however they will need to demonstrate comparable or improved efficacy to established modalities.
In addition to infrastructure and capacity constraints, CAR-Ts face a very different risk-benefit dynamic in autoimmune compared to oncology, highlighting the need for tolerable therapies with low adverse event risk. CAR-NK and Treg-based therapies are also being developed in certain autoimmune disorders and may demonstrate favorable safety profiles. Several novel non-cell therapies such as bispecific antibodies, nanobodies, and RNAi drugs, may also offer future alternative competitive solutions with variable value propositions.
Widespread adoption of cell therapies will not only require strong efficacy and safety data, but also adapted pricing and access strategies. At oncology-based price points, CAR-Ts are unlikely to achieve broad market access in autoimmune disorders, with eligible patient populations that are potentially orders of magnitude greater than the number of currently addressable cancer patients. Developers have made strides towards reducing cell therapy COGS while improving manufacturing efficiency, but payors will inevitably restrict access until more sustainable pricing is achieved.
Despite these headwinds, industry leaders and investors remain confident that cell therapies are poised to address significant unmet need in patients suffering from autoimmune disorders. However, the extent of this impact on the treatment landscape remains to be seen, as the industry rapidly approaches an inflection point.
Adhd Medication Shortage Uk - trinexpharmacy.comreignlana06
The UK is currently facing a Adhd Medication Shortage Uk, which has left many patients and their families grappling with uncertainty and frustration. ADHD, or Attention Deficit Hyperactivity Disorder, is a chronic condition that requires consistent medication to manage effectively. This shortage has highlighted the critical role these medications play in the daily lives of those affected by ADHD. Contact : +1 (747) 209 – 3649 E-mail : sales@trinexpharmacy.com
These lecture slides, by Dr Sidra Arshad, offer a quick overview of the physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar lead (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
6. Describe the flow of current around the heart during the cardiac cycle
7. Discuss the placement and polarity of the leads of electrocardiograph
8. Describe the normal electrocardiograms recorded from the limb leads and explain the physiological basis of the different records that are obtained
9. Define mean electrical vector (axis) of the heart and give the normal range
10. Define the mean QRS vector
11. Describe the axes of leads (hexagonal reference system)
12. Comprehend the vectorial analysis of the normal ECG
13. Determine the mean electrical axis of the ventricular QRS and appreciate the mean axis deviation
14. Explain the concepts of current of injury, J point, and their significance
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. Chapter 3, Cardiology Explained, https://www.ncbi.nlm.nih.gov/books/NBK2214/
7. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
TEST BANK For An Introduction to Brain and Behavior, 7th Edition by Bryan Kol...rightmanforbloodline
TEST BANK For An Introduction to Brain and Behavior, 7th Edition by Bryan Kolb, Ian Q. Whishaw, Verified Chapters 1 - 16, Complete Newest Versio
TEST BANK For An Introduction to Brain and Behavior, 7th Edition by Bryan Kolb, Ian Q. Whishaw, Verified Chapters 1 - 16, Complete Newest Version
TEST BANK For An Introduction to Brain and Behavior, 7th Edition by Bryan Kolb, Ian Q. Whishaw, Verified Chapters 1 - 16, Complete Newest Version
Integrating Ayurveda into Parkinson’s Management: A Holistic ApproachAyurveda ForAll
Explore the benefits of combining Ayurveda with conventional Parkinson's treatments. Learn how a holistic approach can manage symptoms, enhance well-being, and balance body energies. Discover the steps to safely integrate Ayurvedic practices into your Parkinson’s care plan, including expert guidance on diet, herbal remedies, and lifestyle modifications.
TEST BANK For Basic and Clinical Pharmacology, 14th Edition by Bertram G. Kat...rightmanforbloodline
TEST BANK For Basic and Clinical Pharmacology, 14th Edition by Bertram G. Katzung, Verified Chapters 1 - 66, Complete Newest Version.
TEST BANK For Basic and Clinical Pharmacology, 14th Edition by Bertram G. Katzung, Verified Chapters 1 - 66, Complete Newest Version.
TEST BANK For Basic and Clinical Pharmacology, 14th Edition by Bertram G. Katzung, Verified Chapters 1 - 66, Complete Newest Version.
TEST BANK For Basic and Clinical Pharmacology, 14th Edition by Bertram G. Katzung, Verified Chapters 1 - 66, Complete Newest Version.
Promoting Wellbeing - Applied Social Psychology - Psychology SuperNotesPsychoTech Services
A proprietary approach developed by bringing together the best of learning theories from Psychology, design principles from the world of visualization, and pedagogical methods from over a decade of training experience, that enables you to: Learn better, faster!
Here is the updated list of Top Best Ayurvedic medicine for Gas and Indigestion and those are Gas-O-Go Syp for Dyspepsia | Lavizyme Syrup for Acidity | Yumzyme Hepatoprotective Capsules etc
8 Surprising Reasons To Meditate 40 Minutes A Day That Can Change Your Life.pptxHolistified Wellness
We’re talking about Vedic Meditation, a form of meditation that has been around for at least 5,000 years. Back then, the people who lived in the Indus Valley, now known as India and Pakistan, practised meditation as a fundamental part of daily life. This knowledge that has given us yoga and Ayurveda, was known as Veda, hence the name Vedic. And though there are some written records, the practice has been passed down verbally from generation to generation.
Local Advanced Lung Cancer: Artificial Intelligence, Synergetics, Complex Sys...Oleg Kshivets
Overall life span (LS) was 1671.7±1721.6 days and cumulative 5YS reached 62.4%, 10 years – 50.4%, 20 years – 44.6%. 94 LCP lived more than 5 years without cancer (LS=2958.6±1723.6 days), 22 – more than 10 years (LS=5571±1841.8 days). 67 LCP died because of LC (LS=471.9±344 days). AT significantly improved 5YS (68% vs. 53.7%) (P=0.028 by log-rank test). Cox modeling displayed that 5YS of LCP significantly depended on: N0-N12, T3-4, blood cell circuit, cell ratio factors (ratio between cancer cells-CC and blood cells subpopulations), LC cell dynamics, recalcification time, heparin tolerance, prothrombin index, protein, AT, procedure type (P=0.000-0.031). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and N0-12 (rank=1), thrombocytes/CC (rank=2), segmented neutrophils/CC (3), eosinophils/CC (4), erythrocytes/CC (5), healthy cells/CC (6), lymphocytes/CC (7), stick neutrophils/CC (8), leucocytes/CC (9), monocytes/CC (10). Correct prediction of 5YS was 100% by neural networks computing (error=0.000; area under ROC curve=1.0).
2. Objectives
At the end of this session students able to:
• Cardiac fuels in different metabolic states
• Identify cardiac markers
• Identify specific and non specify markers of cardiac injury
by Don. Siyum A. 2
5/7/2022
3. Introduction
the metabolic demand of the heart is the largest of any organ
has minimal Energy reserves:- ATP and Creatine phosphate,
few glycogen. must be continually nourished
ATP provides energy
for contractile work, for pumping Ca2+ into the sarcoplasmic
reticulum, diastolic relaxation, for maintaining ion gradients
(e.g. Na+ and K+)
normal working conditions : 2/3 of the ATP used to fuel
contractile work, with the remaining 1/3 used for ion pumps
by Don. Siyum A. 3
5/7/2022
4. Fig. Metabolic relationships among the major human
organs. Red arrows indicate preferred routes in the well-fed
state by Don. Siyum A. 4
5/7/2022
6. • the heart has a relatively low ATP content (5 μmol/g wet wt) and high
rate of ATP hydrolysis (0.5μ mol · g wet wt -1 · s-1 at rest)
• complete turnover of the myocardial ATP pool every 10 s under normal
conditions
• in the healthy heart, the rate of ATP hydrolysis is matched to the
rate oxidative phosphorylation ( ATP content remains constant )
by Don. Siyum A. 6
5/7/2022
7. Sources of ATP in heart
• The primary means for ATP synthesis is oxidative phosphorylation
in the mitochondria (>98%), glycolysis (< 2%).
• post absorptive state 60–90% of the ATP comes from fatty
acids, and 10–40% comes from pyruvate (formed from lactate
and glycolysis)
by Don. Siyum A. 7
5/7/2022
8. Fig: overview of myocardial energy substrate metabolism.
by Don. Siyum A. 8
5/7/2022
9. Fig: ATP production occurs primarily through oxidative
phosphorylation
by Don. Siyum A. 9
5/7/2022
10. • There is a stoichiometric link between the rate of oxidation of carbon
fuels, NADH and FADH2 reduction, flux through the electron
transport chain, oxygen consumption, oxidative phosphorylation, ATP
hydrolysis, actin-myosin interaction, and external contractile power
produced by the heart.
• Thus an increase in contractile power results in a concomitant
increase in all of the components in the system.
by Don. Siyum A. 10
5/7/2022
11. SUBSTRATES FOR ATP SYNTHESIS
• main types of carbon substrates for myocardial ATP
synthesis: fatty acids, glucose, ketone bodies and
lactate
• myocardial metabolism is linked to arterial carbon
substrate concentration, hormone concentrations,
coronary flow, inotropic state, and the nutritional
status of the tissue
by Don. Siyum A. 11
5/7/2022
12. Fat as source of energy
• the heart readily extracts free fatty acids from the plasma and either
oxidizes them rapidly, or converts them to triglyceride stores.
• 80% of the FFA oxidized to CO2 and 20% converted to
triglyceride
• The rate of uptake dependent upon the concentration of FFA in the
plasma ( 0.2 to 0.8 mM), and the content of a specific fatty acid
transport protein in the sarcolemma membrane
by Don. Siyum A. 12
5/7/2022
13. • plasma fatty acid concentration is regulated by their net release from
triglycerides in adipocytes
• the net balance between triglyceride breakdown by
hormone-sensitive lipase and synthesis by
glycerolphosphate acyltransferase (regulated by
catecholamines and insulin)
• released from triglyceride in chylomicrons and in VLDL by lipoprotein
lipase
by Don. Siyum A. 13
5/7/2022
14. Fig. Hormonal regulation of Triacylglycerol degradation
in Adipocyte
by Don. Siyum A. 14
5/7/2022
15. • Fatty acids enter the cardiomyocyte by:
passive diffusion
protein-mediated transport (fatty acid translocase (FAT
or CD 36) or plasma membrane fatty acid binding protein
(FABP)
• FAT and FABP are associated with Fatty acylcoA synthase (FACS) =
(majority FFA activated)
by Don. Siyum A. 15
5/7/2022
18. • long-chain fatty acyl-CoA, can either be esterified to
triglyceride by glycerolphosphate acyltransferase or
converted to long-chain fatty acylcarnitine by carnitine
palmitoyltransferase I (CPT-I)
• in the healthy normal heart 70–90% of the fatty acids
entering the cell are converted to acylcarnitine and
immediately oxidized, and 10–30% enter the
intracardiac triglyceride pool.
by Don. Siyum A. 18
5/7/2022
19. • The activity of CPT-I is strongly inhibited by malonylCoA, which binds to
CPT-I on the cytosolic side of the enzyme.
• Malonyl-CoA is a key regulator. role of insulin ??
• fatty acids undergo ß-oxidation. What is it ??
by Don. Siyum A. 19
5/7/2022
20. • Most patients who have impaired fatty acid β-oxidation
develop rhabdomyolysis after sustained exercise.
• Those with more severe disease may also have hypoketotic
hypoglycemia in childhood, along with liver dysfunction; those
with the most severe disease may have cardiomyopathy at
birth and die at a young age
by Don. Siyum A. 20
5/7/2022
21. Ketone as source of energy
• The heart extracts and oxidizes ketone bodies (ß- hydroxybutyrate and
acetoacetate)
• during starvation or poorly controlled diabetes, plasma ketone body
concentrations are elevated secondary to low insulin and high fatty
acids
• fatty acids, glucose and lactate uptake and oxidation are inhibited by
elevated plasma ketone bodies with the inhibitory effect mediated
through product inhibition on PDH
by Don. Siyum A. 21
5/7/2022
22. Carbohydrate as source of energy
• heart consumes glucose
• the uptake of extracellular glucose is regulated by:-
the transmembrane glucose gradient
the concentration and activity of glucose transporters in the
plasma membrane
• two isoforms from the glucose transporter identified in the myocardium,
GLUT 1 and GLUT 4, (GLUT 4 is predominant)
by Don. Siyum A. 22
5/7/2022
23. • there is a translocation of glucose transporters in
response to insulin stimulation, increased work
demand, or ischemia ( the effects of insulin and
ischemia are additive)
• translocation of GLUT-4 into the sarcolemma is also
stimulated by activation of AMP-activated protein
kinase (AMPK)
by Don. Siyum A. 23
5/7/2022
24. • an additional source of glucose 6-phosphate for the heart is intracellular
glycogen stores
• the glycogen pool in the heart is relatively small (30 μmol/g wet wt
compared with 150μmol/g wet wt in skeletal muscle)
by Don. Siyum A. 24
5/7/2022
25. Fig. The pathways and regulatory points of myocardial
substrate metabolism
by Don. Siyum A. 25
5/7/2022
26. Lactate as source of energy
• under resting conditions lactate uptake from the blood (MAT-1)
is a major source of pyruvate formation, supplying
approximately 50% of the pyruvate oxidized by the heart
• during physical exercise, lactate can become the predominant
fuel for the heart
• lactate rapidly oxidized by lactate dehydrogenase,
decarboxylated by pyruvate dehydrogenase (PDH) and
oxidized to CO2 in the Krebs cycle
by Don. Siyum A. 26
5/7/2022
27. • the healthy nonischemic heart is a net consumer of
lactate.
• The myocardium becomes a net lactate producer only when there is
accelerated glycolysis in the face of impaired oxidation of pyruvate
like ischemia or poorly controlled diabetes.
by Don. Siyum A. 27
5/7/2022
28. Inter regulation of Fatty Acid and Carbohydrate
Oxidation
• The primary physiological regulator of flux through PDH and the rate of
glucose oxidation in the heart is the rate of fatty acid oxidation
• High rates of fatty acid oxidation inhibit PDH activity
• increase in mitochondrial acetyl-CoA/free CoA and NADH/
NAD, which activates PDH kinase causing phosphorylation
and inhibition of PDH
• Conversely, inhibition of fatty acid oxidation increases glucose and
lactate uptake and oxidation
by Don. Siyum A. 28
5/7/2022
29. • Pyruvate decarboxylation is catalyzed by PDH, and is the key irreversible step
in carbohydrate oxidation
• PDH is located in the mitochondrial matrix,
• inactivatated by phosphorylation
• activated by dephosphorylation
• PDHK is the predominate form in heart, and is rapidly inducible by
starvation and diabetes
by Don. Siyum A. 29
5/7/2022
31. Effects of Substrate Selection on Contractile Function and
Efficiency
• the contractile performance of the heart at a given O2 is
greater when the heart is oxidizing more glucose and lactate,
and less fatty acids
• the theoretical ATP-to-oxygen ratio for glucose or lactate are
3.17 and 3.00, respectively, while for palmitate and oleate the
values are 2.80 and 2.86, respectively
• fatty acid concentrations uncouple oxidative phosphorylation
(decrease the P/O) and cause wasting of O2 by mitochondria
•
by Don. Siyum A. 31
5/7/2022
32. This effect has been demonstrated with
1. lowering plasma free fatty acid by administering an inhibitor of
lipolysis in adipocytes
2. inhibition of CPT-I
3. inhibition of malonylCoA decarboxylase (which elevates malonyl-CoA
content and inhibits CPT-I activity)
4. direct inhibitors of fatty acid -oxidation
• it is important to note that partial inhibitors of myocardial fatty acid
oxidation have been shown to lessen ischemic dysfunction and tissue
damage in animal models of ischemia and reperfusion and have clear
benefits in clinical trials in patients with chronic stable angina
by Don. Siyum A. 32
5/7/2022
33. Metabolism during Myocardial Ischemia and Reperfusion
Myocardial energy metabolism during ischemia is very dependent
upon the duration and severity of ischemia
• Complete elimination of flow results in a rapid depletion of ATP
and Pcr, glycogen, lactate accumulation, and contractile
akinesis, → tissue necrosis and myocardial infarction
• modest reduction in flow (40–60%) causes a decrease in
myocardial oxygen consumption ( l0–50%), a transient
increased dependence on anaerobic glycolysis (glycogen
depletion and lactate production), oxidation of free fatty acids at
a reduced rate, and modest to more severe contractile
dysfunction. by Don. Siyum A. 33
5/7/2022
34. • Despite contractile dysfunction and transient lactate
production during moderate ischemia, the primary oxidative fuel is fatty
acids
Mitochondrial Metabolism in the Failing Heart
• the capacity of the mitochondria for oxygen consumption and oxidative
phosphorylation in failing heart are significantly reduced
• substrate use away from free fatty acids towards glucose
by Don. Siyum A. 34
5/7/2022
36. • A biomarker is a clinical laboratory
• useful in detecting dysfunction of an organ.
• Cardiac biomarkers
• Acute coronary syndrome resulting from myocardial
ischemia
• Congestive cardiac failure due to ventricular dysfunction
• The different markers are used to
• Detect myocardial ischemia at the earliest
• Monitor the progression of the condition
• Predict the risk in cardiac dysfunction
by Don. Siyum A. 36
5/7/2022
37. CARDIAC MUSCLE CELL
by Don. Siyum A. 37
Size and subcellular distribution of myocardial
proteins/enzymes determines time course of biomarker
appearance in the general circulation
5/7/2022
38. An ideal cardiac marker:
1. must be sensitive enough to detect a small degree of
damage
2. should be specific to the heart muscle
3. should give information regarding the severity of the infarct and the
prognosis of the disease
4. should also show the result of reperfusion therapy in AMI
(reversible and irreversible damage)
5. should help in early and late diagnosis
6. should be easy to measure, fast, cheap, and quantitate
7. should have long-term storage conditions and be stable
by Don. Siyum A. 38
5/7/2022
39. • Commonly used biomarkers for early detection of acute
myocardial infarction are:
1. Cardiac troponins, TnI and TnT
2. Creatine kinase, CK-MB
3. Of these, troponins and CK-MB are the most sensitive
and specific markers, whereas myoglobin though
sensitive, is nonspecific
• Predictors of risk in cardiac disease are of two types:
a. For predicting the onset of ischemia
b. Those which quantify the ventricular damage
by Don. Siyum A. 39
5/7/2022
40. Biochemical Changes
by Don. Siyum A. 40
BIOCHEMICAL MARKERS
release of intracellular
contents to blood
clinical manifestations
(chest pain)
ECG
changes
ischemia to myocardial muscles (with low O2 supply)
anaerobic glycolysis
increased accumulation of Lactate
decrease in pH
activate lysosomal enzymes
disintegration of myocardial proteins
cell death & necrosis
5/7/2022
41. TIME LINE OF MARKERS OF MYOCARDIAC DAMAGE &
FUNCTION
by Don. Siyum A. 41
1950 1960 1970 1980 1990 2000 2005
AST in
AMI CK in
AMI
Electrophoresis
for CK and LD
CK – MB
Myoglobin assay
RIA for
ANP
CK-MB
mass assay
cTnT assay
RIA for BNP
and proANP
cTnl assay
RIA for
proBNP
POCT for myoglobin CK-
MB, cTnI
Immuno assay for
proBNP
IMA
Genetic
Markers
Timeline history of assay methods for markers of cardiac tissue damage and myocardial function.
AST: aspartate aminotransferase ANP: atrial natriuretic peptide
CK: creatine kinase BNP: brain natriuretic peptide
LD: lactate dehyydrogenase POCT: point-of-care testing
cTn: cardiac-specific troponin IMA: ischaemia-modified albumin
Time [years]
5/7/2022
42. Aspartate aminotransferase
• The first biomarker used in the diagnosis of AMI, it is not specific to the heart
Lactate dehydrogenase
• LDH has five isoenzymes
• In myocardial infarction, total LDH activity is increased, while H4 isoenzyme is
increased 5–10 times more
• Increase in total LDH level is seen in hemolytic anemias, hepatocellular
damage, muscular dystrophy, carcinomas, leukemias, and any condition which
causes necrosis of body cells
by Don. Siyum A. 42
5/7/2022
43. Tissue distribution of LDH
Iso-enzyme Composition Present in
LDH1 ( H4) Myocardium, RBC, kidney
LDH2
(H3M1)
Myocardium, RBC,
serum, kidney
LDH3 (H2M2) Kidney, Skeletal muscle
LDH4 (H1M3) Kidney, Skeletal muscle
LDH5 (M4) Skeletal muscle, Liver
by Don. Siyum A. 43
5/7/2022
45. • It increases within 6–12 hours from the onset of chest pain, peaks over
1–3 days, and returns to normal values within 8–14 days.
• LDH1:LDH2 ratio >1 is reported to be specific for AMI, but currently it is
not used in the diagnosis of AMI.(Flip pattern)
• Today, the only use of LDH is in distinguishing acute from sub-acute MI
in patients
by Don. Siyum A. 45
5/7/2022
47. Creatine kinase and CK-MB
• Three isoenzymes: CK-BB (CK1), CK-MB (CK2), and CK-MM (CK3). CK-
MM is the dominant form found in all tissue.
• 20% of CK in the myocardium is in the MB form, giving sensitivity and
specificity in the diagnosis of AMI. 5% in skeletal muscle.
• CK-MB reaches its highest point within 24 hours, starting to increase after
4–6 hours, returns to normal within 2 - 3 days
by Don. Siyum A. 47
5/7/2022
49. • the CK level is not increased in hemolysis or in congestive
cardiac failure; CK has an advantage over LDH.
• not used for delayed admission (more than 2 days)
Limitation of CKMB to be a specific marker of AMI
• its increasing level during trauma , Duchenne Muscular
Dystrophy, Polymyositis, Carcinomas (Colon, Lung,
Prostate, Endometrial..), Athletes (e.g. Marathon
runners)…and inflammation
by Don. Siyum A. 49
5/7/2022
53. CK-MB mass
• appears one hour earlier than CK-MB activity (more sensitive)
• So, useful for diagnosis of early cases & re-infarction
• BUT: not for diagnosis of delayed admission cases & less
specific than troponin I
CK-MB relative index
• CK-MB mass/total CK mass × 100
• If this index is 2.5% or above, CK-MB is probably of myocardial origin
by Don. Siyum A. 53
5/7/2022
54. Total CK can be elevated
• False positive (for MI) CK elevation can be seen in:
• Significant skeletal muscle injury
• Significant CNS damage (Stroke/Trauma)
• Occasionally from GI, renal, urologic disease
• Others: injection, hypothermia, exercise, intoxication and
drug abuse
by Don. Siyum A. 54
5/7/2022
55. Myoglobin in diagnosis of AMI
• Myoglobin abundantly present in the heart and skeletal muscle
• It is rapidly released (rises in the first 30 minutes) from the
myocardium during the injury and is rapidly excreted from the
kidneys within 24 hours
• It is elevated in all AMI patients within 6–10 hours and peaks at
the 12th hour. (early detection of AMI)
• It is a sensitive marker for AMI, but has no specificity
• Since it has no specificity, negative values are important in the
clinic, rather than positive values
by Don. Siyum A. 55
5/7/2022
57. • the most important cardiac proteins involved in the diagnosis
of AMI are TnC, TnI and TnT.
• cTnT and cTnI are different from troponins in the skeletal
muscle
• present the cytosolic pool(5%), and the contractile apparatus
(95%)
• the amount of TnC per gram of myocardium is 13–15 times
greater than the amount of CK-MB.
• cTn has higher sensitivity compared to CK-MB in the early
period by Don. Siyum A. 57
5/7/2022
58. • Cardiac troponins are elevated in different clinical conditions,
although their sensitivity and specificity are significantly higher
in detecting coronary ischemia.
• blood levels increase within 2–4 hours after
acute myocardial damage and reach peak levels in 24 hours.
• Blood cTn levels are high for 2 weeks.
by Don. Siyum A. 58
5/7/2022
60. Why is release of troponin prolonged?
• Most is bound to the contractile apparatus of the cardiomyocyte
• 3% of cTnI and 6% of cTnT exist free in the cytoplasm.
• This gives the biphasic response of troponins with a rapid rise and
prolonged elevation.
• The initial elevation of cTnI or cTnT is thought to be a function of the free
cytolsolic form
• The prolonged elevation is caused by degradation of the contractile
pool
by Don. Siyum A. 60
5/7/2022
61. cTnI:
• 100 % cardiac specific
• With greater sensitivity for diagnosing minor damage of MI
• Appears in blood within 6 hours after onset of infarction
• peak: around 24 hours
• Disappears from blood after about one week (stays longer), So, useful
for diagnosis of delayed admission cases
• Prognostic marker (relation between level in blood & extent of cardiac
damage)
by Don. Siyum A. 61
5/7/2022
62. Advantages
• The existence of the cardiac –specific isoform makes them the
most specific of all biochemical markers for cardiac damage.
Highly specific markers of detecting MI
• Higher sensitivity than CK-MB
• Fewer false-positive results in the setting of trauma, surgery, and
renal failure as compared to CK-MB
• Prognostic of death from acute coronary syndrome
by Don. Siyum A. 62
5/7/2022
63. Disadvantages
• It lacks sensitivity in the early hours of AMI
• Pulmonary embolism, congestive heart failure, and myocarditis
can all lead to cardiac troponin elevation
by Don. Siyum A. 63
5/7/2022
64. Brain Natriuretic Peptide (BNP)
• The natriuretic peptide family consists of three peptides:
Atrialnatriuretic peptide (ANP), brain natriuretic peptide
(BNP), and C-type natriuretic peptide (CNP).
• ANP is produced primarily in the cardiac atria.
• BNP is present in human brain, but more in the cardiac
ventricles.
• natriuretic peptides has a strong diuretic effect, promotes
vasodilation, and facilitates cardiovascular remodeling and
response to ischemia
by Don. Siyum A. 64
5/7/2022
66. • Patients with congestive heart failure have high plasma
concentrations of ANP and BNP.
• The concentrations are correlated with the extent of ventricular
dysfunction.
• The best marker of ventricular dysfunction is pro-BNP.
• High concentrations of BNP predict poor long-term survival.
• Normal level of NT-proBNP is less than 400 ng/L.
• Less than 250 ng make heart failure highly unlikely
by Don. Siyum A. 66
5/7/2022
67. Ischemia-modified albumin (IMA) in diagnosis of
AMI
• A structural change in the N-terminus of albumin in patients with
myocardial ischemia was discovered, and this albumin showed lower
metal-binding capacity with cobalt on the albumin–cobalt binding test.
• IMA rise can be detected by this test 3 hours after the appearance
symptoms (sensitivity 70%, specificity 80%, positive predictive value
96%).
• However, the detection of high IMA levels in patients, with cancer,
infection, brain ischemia, liver disease, and, end-stage renal disease limits
the specificity of this test in, the diagnosis of AMI.
by Don. Siyum A. 67
5/7/2022
71. SPECIFICITY OF CARDIAC MARKERS
by Don. Siyum A. 71
50
60
70
80
90
100
TROPONIN-I
70%
87%
92%
99%
CK-MB TOTAL CK MYOGLOBIN
5/7/2022
72. Why do we need multiple Markers?
• No single ideal marker exists
• Complicated diseases are not likely to be associated
with single markers
• Multiple markers define disease categories
• Multi-marker panels can aid in differential diagnosis
by Don. Siyum A. 72
5/7/2022
73. MARKER TISSUE
SOURCE
PHYSIOLOGIC
FUNCTION
“DIAGNOSTIC
WINDOW”
CLINICAL
UTILITY
Creatine
Kinase (CK)
Total Activity
Skeletal
muscle
Cardiac
muscle
Skeletal
muscle
Rephosphorylation
of ADP, forming
ATP in muscle
contraction
Rise: 6-8 hr
Peak: 24-36 hr
Normal: 3-4
days
Limited
diagnostic
value since it is
increased in
various disease
states.
CK isoenzyme
analysis is
more useful for
diagnosis
by Don. Siyum A. 73
5/7/2022
76. MARKER TISSUE
SOURCE
PHYSIOLOGIC
FUNCTION
“DIAGNOSTIC
WINDOW”
CLINICAL
UTILITY
Cardiac
Troponin I
Cardiac
muscle
Muscle contraction
regulatory protein;
bound to
tropomyosin and
actin
Rise 4-8 hr
Peak: 14- 18 hr
Normal: 5-9 days
Highly specific
for myocardial
injury
Useful for
patients with
atypical
symptoms or
those who delay
seeking medical
attention
Potential to
diagnose AMI in
patients who also
have
concomitant
skeletal muscle
trauma/disease
Potential usage
to risk stratify
angina pectoris
by Don. Siyum A. 76
5/7/2022