Heart Pathology 4 PDF

# Heart Pathology 4 ## Dr. Vicheryl Lopez ## Congenital Heart Diseases - refers to abnormalities of the heart or great vessels that are present at birth - majority arises from faulty embryogenesis during gestational weeks 3 to 8 ### Category: - Septal defects, or "holes in the heart" - ASD, VSD...

# Heart Pathology 4 ## Dr. Vicheryl Lopez ## Congenital Heart Diseases - refers to abnormalities of the heart or great vessels that are present at birth - majority arises from faulty embryogenesis during gestational weeks 3 to 8 ### Category: - Septal defects, or "holes in the heart" - ASD, VSD - Stenotic lesions- hypoplastic left heart syndrome - Outflow tract anomalies ## Table 12.2 Frequencies of Congenital Cardiac Malformations | Malformation | Incidence per Million Live Births | % | |---|---|---| | Ventricular septal defect | 4482 | 42 | | Atrial septal defect | 1043 | 10 | | Pulmonary stenosis | 836 | 8 | | Patent ductus arteriosus | 781 | 7 | | Tetralogy of Fallot | 577 | 5 | | Coarctation of the aorta | 492 | 5 | | Atrioventricular septal defect | 396 | 4 | | Aortic stenosis | 388 | 4 | | Transposition of the great arteries | 388 | 4 | | Truncus arteriosus | 136 | 1 | | Total anomalous pulmonary venous connection | 120 | 1 | | Tricuspid atresia | 118 | 1 | | **Total** | **9757** | | ## Congenital Heart Disease - Environmental exposures - congenital rubella infection, teratogens, gestational diabetes - Nutritional factors - folate supplementation during early pregnancy reduces CHD incidence - Genetic factors - most common known genetic cause of CHD- trisomy 21 ### Gene mutations: - GATA4, TBX5, and NKX2-5 - transcription factors that are mutated in some patients with atrial and ventricular septal defects - NOTCH1- bicuspid aortic valve - JAG1 and NOTCH2- tetralogy of Fallot - Fibrillin- Marfan syndrome ## Table 12.3 Selected Examples of Gene Defects Associated With Congenital Heart Disease | Disorder | Gene(s) | Gene Product Function | |---|---|---| | **Nonsyndromic** | | | | ASD or conduction defects | NKX2.5 | Transcription factor | | ASD or VSD | GATA4 | Transcription factor | | Tetralogy of Fallot | ZFPM2 or NKX2.5 | Transcription factors | | **Syndromic** | | | | Alagille syndrome—pulmonary artery stenosis or tetralogy of Fallot | JAGI or NOTCH2 | Signaling proteins or receptors | | Char syndrome-PDA | TFAP2B | Transcription factor | | CHARGE syndrome-ASD, VSD, PDA, or hypoplastic right side of the heart | CHD7 | Helicase-binding protein | | DiGeorge syndrome—ASD, VSD, or outflow tract obstruction | TBXI | Transcription factor | | Holt-Oram syndrome—ASD, VSD, or conduction defect | TBX5 | Transcription factor | | Noonan syndrome—pulmonary valve stenosis, VSD, or hypertrophic cardiomyopathy | PTPN11, KRAS, SOS1 | Signaling proteins | ## Congenital Heart Disease ### Clinical features: 1. **Left-to-right shunt** - ASD, VSD, and patent ductus arteriosus [PDA] A shunt is an abnormal communication between chambers or blood vessels. Abnormal channels permit blood flow down pressure gradients from the left (systemic) side to the right (pulmonary) side of the circulation or vice versa. 2. **Right-to-left shunt** - tetralogy of Fallot (TOF), transposition of the great arteries (TGA), persistent truncus arteriosus, tricuspid atresia, and total anomalous pulmonary venous connection 3. **Obstruction** - coarctation of the aorta, aortic valvular stenosis, and pulmonary valvular stenosis ## Congenital Heart Defects Structural abnormalities of the heart and/or great vessels occurring during fetal development ### Congenital Heart Diseases (CHD) | Right-to-Left Shunt | Left-to-Right Shunt | |---|---| | **Cyanotic** | **Acyanotic** | | Heart defect in which less than normal oxygen levels are delivered to the body | Heart defect in which oxygen levels delivered to the body typically remain normal | ## Diagram of heart with arrows The diagram shows blood flow through the heart. The right atrium (RA) receives deoxygenated blood from the body and pumps it to the right ventricle (RV). The RV pumps the blood to the lungs through the pulmonary valve. The left atrium (LA) receives oxygenated blood from the lungs and pumps it to the left ventricle (LV). The LV pumps the blood to the body through the aorta. ## Eisenmenger Syndrome - Congenital heart defect - Left-to-right shunt - Long standing left-to-right shunt leads to pulmonary hypertension - Reversal to cyanotic right-to-left shunt ## Diagram of Eisenmenger Syndrome The diagram shows the progression of Eisenmenger syndrome. The first stage shows a left-to-right shunt where blood flows from the left side of the heart to the right side. This causes an increase in pressure on the right side of the heart and leads to pulmonary hypertension. The second stage shows a reversal of the shunt, where blood flows from the right side of the heart to the left side. This causes cyanosis, which is a bluish discoloration of the skin due to low blood oxygen levels. ## Diagram of heart showing blood flow and the progression of Eisenmenger Syndrome The diagram shows the blood flow in a normal heart and how it changes in a heart with Eisenmenger Syndrome. The first image shows the typical heart: * Blood flows from the right ventricle to the lungs * Blood flows from the left ventricle to the body * Blood flows from the left atrium to the left ventricle. * Blood flows from the right atrium to the right ventricle. The second image shows how blood flow changes in a heart with a shunt due to a structural defect. This causes increased pressure on the pulmonary artery. The last image shows the reversal of the shunt where the pressure on the pulmonary artery is now so high that it causes the blood to flow back to the right ventricle. This causes deoxygenated blood to flow to the rest of the body, resulting in cyanosis. ## Left-to-Right Shunts - most common CHD ## Atrial Septal Defect - abnormal, fixed openings in the atrial septum caused by incomplete tissue formation that allows communication of blood between the left and right atria - Classification: - ostium secundum (90%) - ostium primum (5%) - sinus venosus (5%) ## Diagram of heart with atrial septal defects The diagram shows the differences between a normal heart and a heart with an atrial septal defect. The normal heart shows a septum between the two atria. In the heart with the atrial septal defect, the septum is missing, allowing blood to flow between the two chambers. Also, the diagram shows the relative location and size of the three different atrial septal defects. ## Atrial Septal Defect - usually asymptomatic until adulthood - less likely to close spontaneously - most common defect to be diagnosed in adults - low mortality ## Diagram of heart with atrial septal defects The diagram shows the differences between a normal heart and a heart with an atrial septal defect. The normal heart shows a septum between the two atria. In the heart with the atrial septal defect, the septum is missing, allowing blood to flow between the two chambers. ## Patent Foramen Ovale A simplified view of a PFO: The diagram shows two hearts, side by side. The heart on the left represents a normal heart with a closed foramen ovale that separates the right atrium from the left atrium. The heart on the right represents a heart with patent foramen ovale (PFO): In a PFO, venous blood is able to leak from the right atrium into the left atrium, and then out to the body. ## Ventricular Septal Defect - most common form of CHD - incomplete closures of the ventricular septum, allowing free communication of blood between the left to right ventricles - CLASSIFICATION: - Membranous-90% - Infundibular - Muscular ## Diagram of heart with ventricular septal defects The diagram shows three hearts, side-by-side. The first shows a normal heart, while the second and third highlight the different types of ventricular septal defect, which are membranous and muscular. ## Picture of heart with the VSD The picture shows a dissected heart with the VSD as a large opening between the right and left ventricles. ## Ventricular Septal Defect - most cases clinically manifest in the pediatric age group are associated with other congenital cardiac anomalies (eg. TOF) - Only 20-30% isolated - if a VSD is first detected only in an adult, it is usually an isolated defect - large defects are usually membranous or infundibular ## Patent Ductus Arteriosus - account for about 7% of cases of CHD - 90% are isolated defects - ductal closure is often delayed (or even absent) in infants with hypoxia or when other congenital defects are present, particularly VSDs ## Diagram of heart with PDA The diagram shows the differences between a normal heart and a heart with a PDA in which blood flows from the pulmonary artery to the aorta. ## Patent Ductus Arteriosus - continuous, harsh "machinery-like" murmur - Therapy: -prostaglandin synthesis inhibitors (Indomethacin) -percutaneous or surgical interventions ## Diagram of heart with PDA The diagram shows the location of the patent ductus arteriosus (PDA) in a heart. ## Diagram of blood flow through the heart with different shunts The diagram shows blood flow through a heart with an ASD, VSD, and PDA. ## Right-to-Left Shunts ## Tetralogy of Fallot ### Cardinal features: 1. VSD 2. Obstruction of the right ventricular outflow tract (subpulmonic stenosis) 3. An aorta that overrides the VSD 4. Right ventricular hypertrophy ## Diagram of heart with tetralogy of Fallot The diagram shows the differences between a normal heart and a heart with tetralogy of Fallot. The normal heart shows a septum between the two ventricles. In the heart with tetralogy of Fallot, the septum is missing, allowing blood to flow between the two chambers and also shows an overriding aorta. ## Tetralogy of Fallot ### Morphology: - "boot-shaped" heart- due to marked right ventricular hypertrophy - VSD is usually large ## Diagram of chest x-ray showing the boot-shaped appearance of a heart with tetralogy of Fallot The diagram shows two chest x-rays of the heart. The chest x-ray on the left shows the boot-shaped appearance of the right ventricle in a heart with tetralogy of Fallot. ## Diagram of heart with tetralogy of Fallot The diagram shows the four main features of tetralogy of Fallot. The first image shows the overriding aorta, the second shows the pulmonary stenosis, the third shows the ventricular septal defect (VSD), and the fourth shows the right ventricular hypertrophy. ## Tetralogy of Fallot - pink tetralogy - subpulmonic stenosis is mild; the abnormality resembles an isolated VSD; shunt may be left-to-right, without cyanosis - classic TOF- With more severe right ventricular outflow obstruction, right-sided pressures approach or exceed left-sided pressures, and right-to-left shunting develops, producing cyanosis - The more severe the subpulmonic stenosis, the more hypoplastic are the pulmonary arteries (i.e., smaller and thinner-walled) and the larger is the overriding aorta. ## Transposition of the Great Arteries - produces ventriculoarterial discordance - Types: - dextro-TGA or d-TGA- more common; aorta arises from the right ventricle, and the pulmonary artery emanates from the left ventricle - levo-TGA or I-TGA- commonly referred to as “congenitally corrected" TGA; does not lead to cyanosis ## Diagram of heart with transposition of the great arteries The diagram shows the differences between a normal heart and a heart with transposition of the great arteries. The normal heart shows the aorta connected to the left ventricle and the pulmonary artery connected to the right ventricle. In the heart with transposition of the great arteries, the aorta is connected to the right ventricle and the pulmonary artery is connected to the left ventricle. ## Diagram of heart with transposition of the great arteries The diagram shows the differences between a normal heart and a heart with transposition of the great arteries. The normal heart shows the aorta connected to the left ventricle and the pulmonary artery connected to the right ventricle. In the heart with transposition of the great arteries, the aorta is connected to the right ventricle and the pulmonary artery is connected to the left ventricle. ## Diagram of heart with congenitally corrected transposition of the great arteries (L-TGA) The diagram shows the anatomy of a heart with congenitally corrected transposition of the great arteries. The aorta is connected to the right ventricle, and the Pulmonary artery (PA) is connected to the left ventricle. The mitral and tricuspid valves are in the normal positions. ## Tricuspid Atresia - complete occlusion of the tricuspid valve orifice - results embryologically from unequal division of the AV canal - mitral valve is larger than normal - right ventricular hypoplasia - cyanosis is present virtually from birth - high early mortality ## Diagram of heart with tricuspid atresia The diagram shows a normal heart and a heart with tricuspid atresia. The normal heart has a tricuspid valve. The heart with tricuspid atresia does not have a tricuspid valve. There is also atrial septal defect and ventricular septal defect. ## Obstructive Lesions ## Coarctation of the Aorta - narrowing, constriction of the aorta - 2x common in males - Turner syndrome frequently affected - 50% of cases-with bicuspid aortic valve and may also be associated with congenital aortic stenosis, ASD, VSD, mitral regurgitation, or berry aneurysms of the circle of Willis - TWO FORMS: - "infantile” form - "adult" form ## Diagram of coarctation of the aorta The diagram shows the differences between a preductal coarctation and a postductal coarctation. The preductal coarctation is located before the ductus arteriosus, and the postductal coarctation is located after the ductus arteriosus. Also, shows a heart with a preductal coarctation, and a heart with a postductal coarctation ## Coarctation of the Aorta Coarctation of the aorta is a narrowing of the aortic lumen, typically just before or after the ductus arteriosus. There is an obstruction of blood flow at the level of the coarctation increases LV afterload. This is often associated with Turner syndrome. ## Diagram of coarctation of the aorta The diagram shows the differences between in a preductal coarctation and a postductal coarctation. The preductal coarctation is located before the ductus arteriosus, and the postductal coarctation is located after the ductus arteriosus. Also, shows a heart with a preductal coarctation, and a heart with a postductal coarctation. ## Coarctation of the Aorta The coarctation of the aorta is a narrowing of the aortic lumen, typically just before or after the ductus arteriosus. There is an obstruction of blood flow at the level of the coarctation increases LV afterload. This is often associated with Turner syndrome. ## Coarctation of the Aorta ### Morphology: 1. **Preductal coarctation** - circumferential narrowing of the aortic segment between the left subclavian artery and the ductus arteriosus - ductus typically is patent band and is the main source of (unoxygenated) blood delivered to the distal aorta - pulmonary trunk is dilated - right ventricle is hypertrophied ## Diagram of coarctations of the aorta The diagram shows the differences between in a preductal coarctation and a postductal coarctation. The preductal coarctation is located before the ductus arteriosus, and the postductal coarctation is located after the ductus arteriosus. Also, shows a heart with a preductal coarctation, and a heart with a postductal coarctation. ## Coarctation of the Aorta ### Morphology: 2. **Postductal coarctation** - aorta is sharply constricted - proximal to the coarctation, the aortic arch and its branch vessels are dilated - left ventricle is hypertrophied ## Diagram of coarctations of the aorta The diagram shows the differences between in a preductal coarctation and a postductal coarctation. The preductal coarctation is located before the ductus arteriosus, and the postductal coarctation is located after the ductus arteriosus. Also, shows a heart with a preductal coarctation, and a heart with a postductal coarctation. ## Coarctation of the Aorta ### Coarctation of the aorta with a PDA - the delivery of unsaturated blood through the PDA produces cyanosis localized to the lower half of the body - many do not survive the neonatal period without surgical or catheter-based intervention to occlude the PDA ### Coarctation of the aorta without a PDA - mostly are asymptomatic - hypertension in the upper extremities with weak pulses and hypotension in the lower extremities, associated with manifestations of arterial insufficiency - Characteristic: “notching" of the undersurfaces of the ribs ## Diagram of rib notching The diagram shows two chest x-rays. The first x-ray highlights the location of rib notching associated with coarctation of the aorta. The second x-ray shows rib notching in a patient with coarctation of the aorta. ## Roesler sign of the coarctation of the aorta ## Pulmonary Stenosis and Atresia ### Pulmonary valve stenosis - Healthy heart - Pulmonary valve stenosis ## Diagram of Pulmonary Stenosis The diagram shows the difference between a healthy heart and a heart with pulmonary valve stenosis. In the healthy heart, the valve opens freely, allowing blood to flow through. The heart with pulmonary valve stenosis shows that the valve fails to open completely, making blood flow difficult. ### Pulmonary atresia Pulmonary atresia is a congenital malformation of the pulmonary valve in which the valve orifice fails to develop. The valve is completely closed thereby obstructing the outflow of blood from the heart to the lungs. ## Aortic Stenosis and Atresia - isolated lesion in 80% of cases - can occur at three locations: - VALVULAR- cusps may be hypoplastic, dysplastic or abnormal in number - SUBVALVULAR- caused by a thickened ring or collar of dense endocardial fibrous tissue below the level of the cusps - SUPRAVALVULAR- congenital aortic dysplasia with thickening and constriction of the ascending aortic wall; Elastin gene mutations ## Diagram of Aortic Stenosis or Atresia The diagram shows a heart with aortic stenosis or atresia. The diagram highlights the location of the stenosis or atresia. The stenosis or atresia can occur in three locations: valvular, subvalvular, or supravalvular. ## Aortic Stenosis and Atresia - Hypoplastic left heart syndrome - severe congenital aortic stenosis or atresia - hypoplasia of the left ventricle and ascending aorta - narrowed or atretic mitral valve or aortic valve ## Diagram of hypoplastic left heart syndrome The diagram shows the differences between a normal heart and a heart with hypoplastic left heart syndrome. The normal heart has a left ventricle and left atrium of normal size. The heart with hypoplastic left heart syndrome has a small left ventricle, a small ascending aorta, and a small mitral valve. ## Arrhythmogenic Cardiomyopathy - autosomal dominant disorder - right-sided heart failure and rhythm disturbances - right ventricular wall is severely attenuated due to loss of myocytes, accompanied by massive fatty infiltration and focal fibrosis - Naxos syndrome- arrhythmogenic cardiomyopathy and hyperkeratosis of plantar and palmar skin surfaces, and is also associated with plakoglobin mutations ## Picture of arrhythmogenic cardiomyopathy - Picture A shows a cross-section of the heart, highlighting the thinning of the right ventricle. - Picture B shows microscopic view of the section of a heart with arrhythmogenic cardiomyopathy. The image shows the replacement of myocardial fibers by fibrofatty tissue. ## Takotsubo Cardiomyopathy - left ventricular contractile dysfunction after extreme psychological stress - “broken heart syndrome” - stress-induced cardiomyopathy - left ventricular apex is most often affected, leading to “apical ballooning" that resembles a takotsubo. ## Diagram of Takotsubo Cardiomyopathy The diagram shows the differences between a normal heart and a heart with takotsubo cardiomyopathy. The normal heart has a normal shape and size. The heart with takotsubo cardiomyopathy has a ballooned appearance, similar to Japanese octopus trap. ## Broken Heart Syndrome The diagram shows the differences between a normal heart and a heart with broken heart syndrome. The normal heart has a normal shape and size. The heart with broken heart syndrome has a ballooned appearance, similar to Japanese octopus trap. ## Picture of Takotsubo Cardiomyopathy The picture shows the microscopic view of a section of a heart with Takotsubo cardiomyopathy. The image shows the characteristic damage to the heart. ## Catterpillar chromatin in nuclei Anitschkow cell - The caterpillar chromatin pattern of the nucleus in longitudinal section ## Picture of Anitschkow cells with caterpillar chromatin in nuclei The picture shows the microscopic view of a section of a heart with Anitschkow cells. The image shows the characteristic appearance of these cells with the caterpillar chromatin pattern. ## Anitschkow cells - caterpillar chromatin pattern of nucleus ## Picture of Anitschkow cells with caterpillar chromatin in nuclei The picture shows the microscopic view of a section of a heart with Anitschkow cells. The image shows the characteristic appearance of these cells with the caterpillar chromatin pattern. ## Thank you and God bless!