Pathology Chapter 12: the Heart
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Pathology Chapter 12: The Heart
Left ventricle is thicker than the right
Cardiomegaly:
- Increased heart weight or thickness indicates hypertrophy
- Enlarged heart chamber size indicates dilation
Myocardium – cardiac muscle
- Made of muscle cells called myocytes
- Sarcomere – heart contractile unit
o Made of:
. Myosin – thick filaments
. Actin – thin filaments
. Regulatory proteins – like troponin and tropomyosin
o Strings of sarcomeres make up the cardiac muscle and give it a striated look
o In contraction, myosin pull neighboring actin toward the center of the sarcomere, which shortens the myocyte
o The amount of force generated is determined by the distance each sarcomere shortens
o Ventricular dilation in diastole increases how much the sarcomere shortens, and therefore the force of contraction during systole
. If you dilate beyond a certain point though, you actually decrease the overlap between the myosin and actin, and so the force of contraction decreases
Hence why lots of dilation can cause heart failure
- Ventricular myocytes are bigger and arranged in a more structured spiral pattern than atrial myocytes, which are arranged haphazardly
- Atrial myocytes can have atrial granules, which store atrial natriuretic peptide (ANP)
o Atrial natriuretic peptide can cause vasodilation, natriuresis (sodium excretion), and diuresis
- Intercalated discs link myocytes, and have gap junctions to allow conduction of heart signals Valve function depends on the mobility and structural integrity of their flaps, called leaflets in the AV valves, or cusps in the semilunar valves
Layers of the heart valves:
- Fibrosa – dense collagenous layer close to the outflow surface
- Spongiosa- central core of loose connective tissue
- Ventricularis/atricularis- elastin rich layer below the inflow surface
- Endothelial layer – acts as a covering
Collagen gives the valve mechanical integrity
The valve consists of interstitial cells that adjust the ECM to allow it to respond and adapt to changes
Main ways to damage a heart valve:
- Damage to collagen – weakens leaflets
- Calcification – starts with the interstitial cells
- Fibrotic thickening
Sinuatrial (SA) node – found near where the right atrium and superior vena cava meet
AV node – found in the right atrium on the atrial septum
- Can delay transmission from the SA node, in order to allow atrial contraction before ventricular
Bundle of His- runs from the right atrium to the top of the ventricular septum
- Then divides into the left and right bundle branches, which run into the ventricles
Autonomics control the pace of the heart
To get energy, myocytes rely almost entirely on oxidative phosphorylation
- To do this, myocytes have tons of mitochondria
- So they need oxygen, so they’re very vulnerable to ischemia
The myocardium gets blood from the coronary arteries
- Run first as epicardial coronary arteries on the surface of the heart
- When they enter the myocardium, they’re called intramural arteries 3 major epicardial arteries:
- Left anterior descending artery (LAD)
o Its branches are called diagonal, and septal perforators
- Left circumflex artery (LCX)
o Its branches are called obtuse marginals
- Right coronary artery
How aging affects the heart:
- The amount of epicardial fat increases
- The size of the left ventricle outflow tract decreases
- Valves calcify, and can thicken through fibrosis
o Mitral leaflets can buckle back into the left atrium, causing symptoms similar of a prolapsed (aka myxomatous) mitral valve
- There will be less myocytes, increased collagenized connective tissue, and deposition of amyloid
- Lipofuscin deposits, that can lead to brown atrophy
- Vessels get atherosclerotic
Problems that cause heart issues:
- Failure of the pump – most common, not enough blood gets out of the heart
- Obstruction to flow through vessel or heart
- Regurgitant flow – part of the output from a chamber contraction, moves backwards into the chamber
- Shunted flow
- Conduction problems
- Rupture of the heart or a major vessel
Congestive heart failure (CHF) – means heart failure
- Heart can’t pump enough blood out to the tissues
- Most commonly, heart failure is caused by progressive decrease in the heart’s ability to contract (called systolic dysfunction) o Diastolic dysfunction – heart chambers can’t expand and fill enough during diastole
Things body does to increase blood to tissues:
- Frank-Starling mechanism – increased filling volume dilates the heart, which increases the cross- bridge formation in the sarcomeres, which ↑ contractility (what goes in gets pumped out)
- The heart adjusts itself – includes hypertrophy and ventricular remodeling
- Activating sympathetics – increases cardiac output
o Includes:
. Release of norepinephrine by adrenergic cardiac nerves – increases heart rate and contractility
. Activating renin-angiotensin-aldosterone system
. Release of atrial natriuretic peptide
Heart hypertrophy is when the myocytes increase in size, which can cause an increase in heart weight
- Can be caused by a pressure or volume overload causing increased work by the heart
o Pressure-overload hypertrophy- causes increase in ventricle thickness, and sarcomeres are arranged in parallel
o Volume-overload hypertrophy- causes ventricles to dilate, and sarcomeres are arranged in series
- Can also be caused by signals stimulating the heart
o Ex: β-adrenergic receptors
Heart hypertrophy is dependent on protein synthesis, which allows for the making of more sarcomeres
- Hypertrophic myocytes also have increased mitochondria and a bigger nucleus
As the hypertrophied heart increases in size, it needs more oxygen, but the amount of heart capillaries doesn’t increase, so it’s harder for the heart to get enough oxygen
Prolonged hemodynamic load can cause a shift to fetal heart actions, including converting to β myosin heavy chains, as well as release of ANP
Heart hypertrophy causes increased metabolic demands
- Makes the heart vulnerable to decompensation, leading to heart failure
When the heart hypertrophies, the initially beneficial changes can lead to heart failure - Includes:
o Changes in heart metabolism
o Changes in movement of calcium ions
o Apoptosis of myocytes
o Reprogramming of gene expression
Increased heart mass is a risk factor for mortality and sudden death
Physiologic hypertrophy in exercise:
- Cardio causes volume-load hypertrophy, with increased amounts of capillaries
o Also decreases heart rate and blood pressure, so all of this is good effects
- Static exercise (like lifting weights) can cause pressure hypertrophy and can cause unwanted changes
Heart failure usually causes decreased cardiac output, decreased tissue perfusion, and pooling of blood in the veins, which can cause pulmonary and/or peripheral edema
Because the cardiovascular system is a closed circuit, failure on one side of the heart usually causes increased load on the other side of the heart, leading to heart failure
Left sided heart failure is most often caused by Ischemic heart, Hypertension, Aortic or mitral valve disease, or Heart disease
Morphology of left sided heart failure:
- Usually causes congestion of the pulmonary circulation, stasis in the left heart, and hypoperfusion of tissues
- In the heart:
o Usually hypertrophied and/or dilated
o Can have areas of infarcts or regurgitations
o Hurt left ventricles can cause dilation of the left atrium, which can causes afib
. Afib causes stasis, which can allow a thrombus to form
- In the lungs:
o Pulmonary congestion and edema causes wet, heavy lungs o The pulmonary edema include RBCs and cause hemosiderin-filled macrophage called heart failure cells
- Left sided heart failure starts with cough and dyspnea, first at exercise, and then at rest
o More pulmonary edema can cause orthopnea (difficulty breathing when lying down), or paroxysmal nocturnal dyspnea
o Decreased cardiac output causes less renal perfusion, so the renin-angiotensin- aldosterone system gets activated to hold onto salt and water, increasing fluid volume
. The increased pressure from this can cause pulmonary edema
o Cerebral hypoxia can cause hypoxic encephalopathy, with irritability, lack of focus, and restlessness, leading into confusion or coma
- Systolic left failure – pump don’t work
- Diastolic left failure – cardiac output is normal at rest, but the left ventricle is stiff and can’t relax during diastole
o So heart can’t increase cardiac output when it needs to
o Also, since the left ventricle can’t expand, any increase in filling pressure causes pulmonary edema
Right-sided heart failure:
- Usually caused by left-sided heart failure, due to increased pulmonary pressure causing more work on the right heart
o Therefore, anything that causes left-sided heart failure, can lead to right-sided heart failure
- Right-sided heart failure by itself is called cor pulmonale
o Usually caused by a pulmonary problem, most often pulmonary hypertension
o Pulmonary hypertension causes hypertrophy and dilation of the right heart
- Right-sided heart failure differs from left-sided in that instead of pooling of blood in the lungs, there’s pooling of blood in the veins
- Morphology:
o In the heart – usually hypertrophy and dilation
o Liver and portal system – congestion that can hurt the system . Liver is usually enlarged, called congestive hepatomegaly
Causes nutmeg liver, where the center of the lobule is hypoxic
Can lead to cardiac sclerosis and cardiac cirrhosis
. Portal hypertension causes the spleen to enlarge, called congestive splenomegaly
o In body cavities – causes accumulations of fluid called effusions
. Effusions can cause poor lung inflation, leading to atelectasis
. Effusion into the peritoneum is called ascites
o Subcutaneous tissue- will show edema of peripheral parts of the body
- The same mental problems from left heart failure also occur in right heart failure
Drugs to help with heart failure:
- Diuretics- relieve fluid overload
- Angiotensin converting enzyme (ACE) inhibitors – block angiotensin-renin-aldosterone system
- β-adrenergic blockers – block sympathetics
Congenital heart disease – heart deformities you’re born with
- Usually happens during weeks 3-8 of development
- The most common congenital heart disease is ventricular septal defects
Heart development – p. 538
- Heart precursors originate in lateral plate mesoderm and move to the mid-line in one of two waves as either a first or a second heart field
o The first heart field expresses TBX5 and Hand1, gives rise to the left ventricle
o The second heart field expresses Hand 2 and fibroblast growth factor 10, and give rise to the outflow tract, right ventricle, and most of the atria
o Both fields have multipotent progenitors that form endocardium, myocardium, and smooth muscle
- The heart fields then form a tube that loops to the right to start forming the heart chambers - Cells derived from the neural crest then migrate into the outflow tract to help form the septum of the outflow tract, and form the aortic arches
- At the same time, ECM of the future AV canal and outflow tract enlarges into swellings called endocardial cushions
o The endocardial cushions help form the valves and the heart chambers
- Important signaling pathways for heart development:
o Wnt, VEGF, Bone morphongenic factor, TGF-β, Fibroblast growth factor, and Notch
o Often, a heart defect is caused by an autosomal dominant mutation to cause a loss of one of these pathways
- Congenital heart defects are usually caused by sporadic gene mutations
- Page 539
o Marfan’s syndrome is caused by a problem with fibrillin, which down regulates TGF-β
. So marfan’s causes excess TGF-β, causing valve problems and aortic aneurysm
o DeGeorge syndrome has a 22q11.2 chromosome deletion in half of affected people
. In DeGeroge syndrome, the fourth branchial arch, and derivatives of the third and fourth pharyngeal pouches, don’t develop right
. All of those are involved in heart making
- Most common cause of congenital heart disease is trisomy 21 (Down’s syndrome)
o Usually affects things from the endocardial cushions, like the AV septum or the valves
- Children of people with a congenital heart defect, have an increased risk of having a congenital heart defect
3 categories of congenital heart defects:
- Obstructions
- Left-to-right shunts- cause increased pulmonary flow, which can increase pulmonary pressure
o Can lead to right ventricular hypertrophy, and atherosclerosis of the pulmonary vessels
- Right-to-left shunts – causes cyanosis from poorly oxygenated blood
Shunt – abnormal communication between chambers or blood vessels Right-to-left shunts allow easy routes for paroxysmal embolisms to reach the arteries
Severe, chronic cyanosis in right-to-left shunts can cause clubbing of the tips of the fingers and toes, and polycythemia (increased RBCs)
- Clubbing is called hypertrophic osteoarthropathy
In left-to-right shunts, the pulmonary arteries constrict to prevent edema and keep pulmonary pressure normal
- Prolonged vasoconstriction causes proliferation of vascular wall cells, leading to lesions like those in hypertension, increasing the resistance
- The increased resistance can increase pulmonary pressure enough to convert the shunt from left-to-right, to right-to-left
o Called late cyanotic congenital heart disease, or Eisenmenger syndrome
Once pulmonary hypertension develops, structural defects of congenital heart disease are irreparable
- This is why you have to catch them early to fix them surgically
Atresia- complete obstruction
Hypoplasia- decrease in volume and muscle mass before birth
- Similar to atrophy after birth
Left-to-right shunts - Atrial septal defect, patent foramen ovale, ventricular septal defect, AV septal defect, and patent ductus arteriosus – page 540
- Atrial septal defects- opening in atrial wall, connecting left and right atria
o Usually asymptomatic until adulthood, can be fixed to give a good prognosis
o 3 types:
. Secundum ASDs – almost all ASDs, near center of septum
. Primum anomalies- near AV valves
. Sinus venosus defects – near superior vena cava
o Cause left-to-right shunting because pulmonary resistance is less than systemic, and because the right ventricle is more compliant (stretchy) than the left
- Patent foramen ovale o Formane ovale is an important right-to-left shunt in fetal life that lets oxygen rich blood from the placenta skip the lungs and go to the left heart
. Usually closed by increased left heart pressure when you start breathing
o Pulmonary hypertension, or quick rises in right-to-left pressures like in sneezing or coughing, can cause brief moments of right-to-left shunting in a patent foramen ovale
- Ventricular septal defects - allows blood to move between the ventricles
o Most common congenital heart defect
o Most happen with other heart defects there too
o Most VSDs happen at the membraneous interventricular septum
o How bad the VSD is depends on the size of the defect, & what it does to the right heart
. Large ones cause problems right away, while smaller ones may take years to notice
o VSDs cause left-to-right shunting, which can cause right ventricular hypertrophy and pulmonary hypertension
o Over time, irreversible pulmonary vascular disease causing shunt reversal, cyanosis, and death
- Patent ductus arteriosus
o In fetal life, the ductus arteriosus shunts blood from the pulmonary artery to the aorta, in order to bypass the lungs
o So in patent ductus arteriosus, blood goes from the aorta into the pulmonary artery
o Most patent ductus arteriosus happen by themselves, without other defects present
o Patent ductus arteriosus causes a murmur called a “machine-like” murmur
o Usually asymptomatic at birth
o Pressure and volume overload from the left-to-right shunt cause obstructions in the pulmonary arteries, causing a reversal to a right-to-left shunt
- Atrioventricular septal defect (aka complete atrioventricular canal defect)
o Caused by failure of the endocardial cushions of the AV canal to fuse right
o The open AV septum causes problems with making the valves o 2 most common forms:
. Partial AVSD – causes a primum atrial septal defect, and a cleft mitral leaflet
. Complete AVSD- causes a big atrioventricular septal defect and a big common AV valve
In this one, all 4 chambers are connected, so they all hypertrophy
Common in Down syndrome
Right-to-left shunts- tetralogy of fallot, transposition of the great arteries, patent truncus arteriosus, tricuspid atresia, and total anomalous pulmonary venous connection
- Right to left shunts cause cyanosis at birth
- Tetralogy of Fallot
o Has 4 main features:
. Ventricular septal defect (VSD)
. Obstruction of right ventricular outflow tract into the lungs (pulmonary valve or infundibulum stenosis)
. The aorta overrides the VSD
. Right ventricular hypertrophy
o Caused by displacement of the infundibular septum (conotruncal)
o The severity of tetralogy of Fallot depends on the degree of the pulmonary stenosis
. A mild stenosis is called pink tetralogy, because it’s similar to a VSD, with a left- to-right shunt, and no cyanosis
. The more stenosed it gets, the more resistance to right ventricular outflow, creating more pressure in the right heart
When right heart pressure gets to be more than left, the shunt becomes a right-to-left shunt, causing cyanosis
Called classic tetralogy of Fallot
The heart increases in size as the child grows
. The right heart won’t fail, because it can shunt the blood to the left
The stenosis also protects the pulmonary vessels from the high pressure - Transposition of the great arteries – switches where the 2 outflow arteries are
o Transposition of the great arteries (TGA) switches up where things are in the heart:
. The aorta arises from the right ventricle instead of the left
. The pulmonary artery arises from the left ventricle, instead of the right
o The heart chambers are still normal, their outflow tract is just connected to something different
o Caused by a problem with truncal and aortopulmonary septum formation
. This causes a separation between the systemic and pulmonary circulations, which will cause death unless there’s a shunt
o Severity depends on how much mixing of blood there is, how much blood gets to the tissues, and the ability of the right heart to handle pumping blood to the system
o The right ventricle hypertrophies, and the left ventricle atrophies
o Without surgery, most children die within months
- Persistent truncus arteriosus
o Caused by problem with the truncus arteriosus to separate into the pulmonary trunk and aorta
. So you get one big artery getting blood from both ventricles, and controlling systemic, pulmonary, and coronary circulation
o Usually comes with a VSD
o Leads to cyanosis from right-to-left mixing of blood, and increased pulmonary flow, causing irreversible pulmonary hypertension
- Tricuspid atresia - complete occlusion of the tricuspid valve
o Happens when the AV canal doesn’t divide equally, so the mitral valve is bigger than normal, and there’s hypoplasia (underdevelopment) of the right ventricle
o Usually comes with an ASD and a VSD
o Cyanosis is present from birth
o High mortality rate in first weeks of life - Total anomalous pulmonary venous connection (TAPVC) – when the pulmonary veins don’t directly connect to the left atrium
o Caused by the common pulmonary vein not developing, or it becomes atretic
o Always accompanied by either a patent foramen ovale or ASD, to let blood get to the left ventricle
o Causes volume and pressure hypertrophy, and dilation of the right heart and pulmonary trunk
. Left ventricle is normal, left atrium is hypoplastic
o Can show cyanosis
Obstructive congenital anomalies
- Coarctation – means narrowing, or constriction
- Coarctation of the aorta
o Affects more males than females
o Two forms:
. Infantile form- has hypoplasia of the aortic arch near a patent ductus arteriosus, early in childhood
. Adult form –infolding of the aorta near what once was the ductus arteriosus, called the ligamentum arteriosum
o Half of the time, coarctation of the aorta also presents with an aortic valve with only 2 cusps (bicuspid)
o The coarctation is after the branches of the aorta that lead to the upper body, so it decreases blood to the lower body
o If there’s a coarctation of the aorta, and a patent ductus arteriosus, it can cause problems right away after birth and need surgery
. Causes cyanosis to the lower body
o If there’s coarctation with no ductus arteriosus, children can live into adulthood
. There’s hypertension in the upper extremities, and lower pressure in the lower body
. Collateral circulation will develop around the coarctation o Can cause left ventricle hypertrophy, and murmurs in systole
- Pulmonary stenosis and atresia will cause right ventricular hypertrophy
o If totally atretic, there’s no connection between the right ventricle and the lungs
. This usually causes right ventricular atrophy , and a patent ductus arteriosus
o Can be asymptomatic, or require surgery
- Aortic stenosis and atresia
o Can happen at the valve, above it, or below it
o Obstruction to the left ventricular outflow tract causes underdevelopment of the left ventricle and ascending aorta
. Also causes the ductus arteriosus to stay open to allow blood to the aorta
. All of this is called hypoplastic left heart syndrome
Almost always fatal in the first week of life when the ductus closes, so surgery is needed
o Usually comes with a facial anomaly
Ischemic heart disease is the leading cause of death worldwide
Ischemia is more severe than hypoxia, because it prevents any nutrients for anaerobic glycolysis as well, so there is no way to produce energy
Hypoxia is only lack of oxygen, but nutrients still get to the tissue, just not oxygen
Most cases of myocardial ischemia are caused be decreased blood flow from an obstructive atherosclerotic lesion in the coronary arteries
- This is why ischemic heart disease is often called coronary artery or heart disease
- These events take place starting in childhood or adolescence, and accumulate until problems manifest later in life
The main cause of ischemic heart disease is not enough blood getting to the heart to meet the heart’s demand
- Usually caused by chronic atherosclerosis in the epicardial coronary arteries, acute change in a plaque, and thrombus or vasospasm - Usually, an atherosclerotic lesion of 75% or more of the lumen will causes symptoms during exercise
o Main symptom is usually angina (chest pain)
o Occlusion of 90% can lead to symptoms at rest
o If the atherosclerotic plaques occlude slowly, collateral vessels may form to prevent infarction
- The 3 main vessels for atherosclerosis in the heart are the LAD, LCX, and the right coronary artery
o Plaques are usually at the beginning of the LAD and LCX, and throughout the entirety of the right coronary artery
- Acute coronary syndromes are usually caused by a stable atherosclerotic plaque quickly converting to an unstable, life-threatening plaque
o Examples of acute coronary syndromes are unstable angina and acute MI
o Plaque becomes unstable if it undergoes superficial erosion, ulceration, fissuring, or deep hemorrhage
o These cause the making of a thrombus that occludes the artery
Angina pectoris - literally means chest pain
- It’s usually used to describe transient attacks of chest discomfort
- The discomfort is usually described as constricting, squeezing, choking, or knifelike
- It’s caused by short lasting heart ischemia that wasn’t bad enough to cause necrosis
- There’s 3 types of angina pectoris:
o Stable (aka typical) angina
o Prinzmetal variant angina
o Unstable (crescendo) angina
- Stable angina is caused by increased demand from the heart, that can’t be met by an occluded coronary artery
o Usually there’s no plaque disruption
o It’s the most common form of angina o Increased demand can be caused by exercise, strong emotions, etc.
o Stable angina is usually relieved by rest, which decreases the demand
. Can also use nitroglycerin or other vasodilators
- Prinzmetal variant angina – uncommon angina caused by coronary artery spasm
o The attacks have nothing to do with physical activity, heart rate, or blood pressure
o Usually responds to nitroglycerin and calcium channel blockers
- Unstable angina is caused by plaque rupture, with an occlusive thrombus and vasoconstriction, all severely decreasing coronary artery flow
o There’s increasingly frequent pain, that starts lasting longer, and is caused by less and less physical activity, to the point where it can occur at rest
o Unstable angina is usually a warning the an acute MI is imminent
o When the term “unstable” is added to something, it means it’s no longer stable, so something has changed to where the condition is not ok anymore
Myocardial Infarction (MI, aka heart attack):
- An MI is the death of cardiac muscle due to prolonged ischemia
- Men are slightly more at risk for an MI than women
o During reproductive years in women, increased estrogen levels protect against heart disease
o After menopause, women become very at risk for heart disease
- A typical MI goes like this:
o A sudden acute change of an atherosclerotic plaque
. With hemorrhage, erosion, ulceration, rupture, or fissuring possible
o Platelets adhere to exposed subendothelial collagen and necrotic plaque stuff, and become activated to form a thrombus
o Platelets can then release mediators to cause vasospasm
o Tissue factor is then activated to cause more clot making
o Within minutes, the thrombus grows enough to occlude the vessel - In a minority of MI’s, a transmural MI occurs, which includes:
o Vasospasm with or without coronary atherosclerosis
o Emboli
o Ischemia without atherosclerosis or a thrombus
- In an MI, the lack of blood to the heart causes ischemia that can lead to myocyte death
o Ischemia leads to an attempt at anaerobic metabolism, which can cause build up of lactic acid
o When even that fails, there’s no making of high energy phosphates like ATP and creatine phosphate
o Because the heart depends on oxygen so heavily, it doesn’t take long for problems to show up when there’s a lack of oxygen to the heart
o Up until 20-30 minutes, myocardial ischemia can be reversible
o In irreversible ischemia, the myocytes undergo necrosis
. Their membranes lose their integrity, letting cardiac enzymes leak out
. Prolonged irreversible ischemia then causes microvascular injury
o In most cases of acute MI, permanent damage happens when you go 2-4 hours without oxygen
- Ischemia is worse in the subendocardium, so irreversible ischemia happens here first
- Knowing the areas the coronary arteries supply helps diagnose where the MI is:
o The left anterior descending branch of the left coronary artery (LAD)
. Supplies most of the apex of the heart (the distal end of the ventricles), the anterior wall of the left ventricle, & the anterior 2/3 of the ventricular septum
o The coronary artery that supplies the posterior 1/3 of the ventricular septum is called “dominant”
. Can be either the right coronary artery or the left circumflex artery
. In right dominant people (most of people): the left circumflex supplies the lateral wall of the left ventricle
the right coronary artery supplies the entire right ventricular wall, the posterior of the left ventricle, and the posterior 1/3 of the ventricular septum
o So occlusion of the right coronary artery causes left ventricular damage
o Collateral anastomoses connect the right and left coronary arteries
. Usually, not much blood flows through the collateral vessels
. When one coronary vessel is occluded, high to low pressure causes more blood through the collateral vessels, causing them to enlarge
- Most MI’s are transmural, which means they involve most of, or all of, the ventricular wall
o Usually involves a combo of chronic coronary atherosclerosis, acute plaque change, and superimposed thrombus on the plaque
o On an EKG, there will be ST elevation, so it’s aka an ST elevated MI (STEMI)
o Transmural MI’s will affect the entire area the occluded coronary vessel supplies
- Subendocardial (nonmural) MI’s involve the inner 1/3 to ½ of the ventricular wall
o The subendocardial zone usually gets the least amount of blood, and most vulnerable to reduced blood flow
o Usually involves plaque change with a thrombus
o The infarct is limited to the area of the coronary artery that suffered the plaque change
o Systemic hypotension can also cause a subendocardial MI
o On an EKG, the ST is fine, so it’s aka a non-ST elevated MI (NSTEMI)
- Morphology:
o An occlusion of the LAD is ½ of all infarcts
. Will involve the anterior wall of the left ventricle, the anterior ventricular septum, and the apex
o An occlusion of the right coronary artery is about 1/3 of infarcts . Involves the inferoposterior wall of the left ventricle, the posterior ventricular septum, and sometimes the inferoposterior wall of the right ventricle o An occlusion of the left circumflex coronary artery is about 1/5 of infarcts
. Involves the lateral wall of the left ventricle (except the apex) o What the MI looks like depends on how long the patient survives following the MI
. Usually, the tissue follows a pattern of ischemic necrosis, inflammation, and repair
. MI’s less than 12 hours old are usually not apparent on a gross examination
You can stain with triphenyltetrazolim chloride (TTC) to find the infarct
o TTC stains normal tissue with lactate dehydrogenase in it red, so the infarct would look unstained and pale, because the dehydrogenase leaked out during ischemic necrosis
. At 12-24 hours, an infarct looks reddish-blue, caused by stagnant, trapped blood
. For days after, the infarct gets tanner looking (necrosislosing enzyme)
. For weeks after, granulation tissue moves in to make a fibrous scar
. Histologically:
Coagulative necrosis is noticed in the first 6-12 hours
Vacuolar degeneration, called myocytolysis, is seen
o Means large vacuolar spaces in cells containing water, are seen
Between 1-3 days, acute inflammation starts
The macrophage remove the necrotic myocytes within a week
Granulation tissue moves in by the 2nd week, leading to fibrous tissue
. the infarct heals from the margin towards the center
Due to inflammatory cell migration through blood vessels, which usually only survive at the periphery
. Once the infarct heals, you can’t tell the age anymore
. Infarcts can expand beyond their original borders through repetitive necrosis in adjacent regions, called extension In this case then, the center zone heals quicker than the periphery
- You can “rescue” ischemic myocardium that hasn’t undergone necrosis yet
o Most effective way to do this is to restore blood flow, as quickly as possible, called reperfusion
. Reperfusion can often be accomplished, but can also trigger bad things like arrhythmias, hemorrhage, reperfusion injury, and myocardial stunning
o Can use coronary intervention through thrombolysis, angioplasty, etc. as well
. The efficiency of these techniques depends on how quickly the obstruction can be alleviated, and how much it will affect everything involved in the occlusion
Ex: thrombolysis can remove a thrombus occluding an artery, but won’t affect the underlying atherosclerotic plaque, while a stent could help both
o Severe ischemia won’t cause immediate cell death, and not all of the myocardium will be equally ischemic
. Because of this, reperfusion after certain time intervals can either save the myocardium from necrosis, or save part of the myocardium from necrosis
o Reperfused infarcts:
. A reperfused infarct is usually hemorrhagic – the blood vessels get injured in ischemia, and leak when blood flow is restored
. Reperfusion not only salvages reversibly injured cells, but can also alter the morphology of irreversibly injured cells
Irreversibly injured myocytes will show contraction bands from exaggerated contraction upon reperfusion
. Reperfusion injury- when irreversible cell damage happens on top of the already present ischemic necrosis, when there’s reperfusion
Caused by oxidative stress, calcium overload, and inflammation, all triggered by the reperfusion
Can cause endothelial swelling that occludes capillaries (called no-flow)
. Stunned myocardium – long period of reversible myocyte injury caused by ischemia . Reperfusion can cause arrhythmias
. Page 554
- Clinical features of an MI
o Rapid, weak pulse
o Diaphoresis – lots of sweating
o Dyspnea -impaired contractility of the ischemic myocardium causes pulmonary congestion and edema
o Can be completely asymptomatic and only noticed on an EKG or lab tests
. Called a “silent” MI
o Lab evaluation of an MI involves looking for things leaked out of necrotic myocytes:
. Myoglobin
. Cardiac troponins T and I
. Creatine kinase MB (CK-MB)
. Lactate dehydrogenase
. Increased levels of these indicates an MI
. The most sensitive and specific markers of heart damage are troponins T and I
They regulate calcium-dependent contraction of cardiac and skeletal muscle
Only found in blood after an MI
Their levels start to rise at 2-4 hours, and peaks at 48 hours
They’ll stay high for 7-10 days
. Creatine kinase can be MM, MB, BB
MM – found in cardiac and skeletal muscle
BB- in the brain and lungs
MB – mainly in heart muscle o So CK-MB is sensitive, but not specific for a heart problem, since it can also be raised when there’s skeletal muscle problems
o CK-MB begins to rise within 2-4 hours of an MI, and peaks at 24 hours, then returns to normal within 3 days
. Troponins and creatine kinases will peak earlier in tissues that get reperfused, since blood comes in to wash out the necrotic tissue quicker
. If levels of troponins or creatine kinases don’t change for 2 days, then it’s not an MI
- Consequences and complications of an MI:
o Half of deaths associated with an acute MI happen within an hour – most never make it to the hospital
o To treat acute MI you give them:
. Aspirin
. Heparin – both it and aspirin prevent clot formation
. Oxygen- to help with the ischemia
. Nitrates – vasodilation
. β-blockers – block β adrenergic receptors to decrease demand for nutrients by myocytes)
. ACE inhibitors – limit ventricular dilation
. Fibrionlytic agents
. Angioplasty
o Things that indicate a poor prognosis with MI:
. Older age, female, diabetes, and previous MI
o When these fail, acute MI can cause:
. Contractile dysfunction-MI’s cause problems with left ventricle function
Left ventricle failure leads to hypotension, and pulmonary congestion and edema, leading to respiratory problems Large MI’s can cause severe left ventricle failure, leading to cardiogenic shock
. Arrhythmias – caused by irritation or conduction problems after an MI
. Myocardial rupture – caused by softening and weakening of the inflamed and necrotic myocardium
Rupture of the ventricular free wall is most common, usually within a week of the MI
o Anterolateral part is the most common site on the wall
Can also have rupture of the ventricular septum, causing a left-to-right shunt, or papillary muscle rupture, causing mitral regurgitation
Usually rapidly fatal
. Pericarditis- develop within 2-3 days due to inflammation
. Right ventricular infarction- usually caused by left heart failure
Causes right heart failure, pooling of blood in the veins, and systemic hypotension
. Infarct extension – usually associated with a mural thrombus
. Mural thrombus- caused by poor contraction leading to stasis, and endocardial damage allowing a procoagulant surface
. Ventricular aneurysm- bulging of scar tissue on the ventricular wall during systole
Happens in myocardium
False aneurysm- happens in epicardium
. Papillary muscle problems
. Progressive heart failure
. The risk for any of these depends on the infarct size, location, and how deep in the heart it is o Large transmural infarcts have a high risk for cardiogenic shock, arrhythmia, and late heart failure o Anterior transmural infarcts have a high risk for rupture, expansion, mural thrombi, and aneurysm
o Posterior transmural infarcts have a high risk for conduction blocks (that’s where SA and AV node are) and right heart problems
o Anterior infarcts are worse than posterior infarcts
o When part of the heart has an infarct, the noninfarcted parts hypertrophy and dilate, called ventricular remodeling
. This helps at first, but then it increases heart demand to a point the heart can’t meet, so it worsens the ischemia and hurts the heart more
o Long term prognosis of an MI depends on how well the left heart is working, and how bad any obstructions to perfusion are
. 1/3 pass away within a year after
. Risk for death increases every year after by a small %
- Page 558
Chronic Ischemic Heart Disease (ischemic cardiomyopathy):
- Chronic ischemic heart disease means progressive heart failure due to heart ischemia
- Most cases involve a prior MI, due to a decrease in function of the hypertrophied noninfarcted area trying to compensate
Sudden cardiac death – unexpected death from heart issues, in patients who showed no symptoms
- Usually caused by a lethal arrhythmia, most commonly caused by acute heart ischemia
- Usually there is a critical coronary stenosis in one of the major coronary vessels
- Less than half of sudden cardiac deaths involve an MI
- Channelopathies are caused by mutations in genes needed for normal ion channel function
o These ions are what control the electrical conducting currents for heart contraction
o Includes long QT syndrome
o They can often cause arrhythmias
Hypertensive heart disease is caused by increased demand on the heart caused by hypertension
- Hypertension causes pressure overload and ventricular hypertrophy - Usually affects left heart from systemic hypertension
- Pulmonary hypertension can cause cor pulmonale in the right heart
Systemic (left-sided) hypertensive heart disease:
- The systemic hypertension causes left heart hypertrophy, as a response to pressure overload
- Can cause heart problems, heart dilation, heart failure, and sudden death
- To diagnose systemic hypertensive heart disease, there will be:
o Left ventricular hypertrophy
o History of hypertension
- ¼ of people have enough hypertension to cause left ventricle hypertrophy
- Hypertension induces left ventricle pressure overload hypertrophy, initially without ventricular dilation
o Left ventricle hypertension can cause thickening that decreases filling, causing left atrial hypertrophy
- The earliest change you can see microscopically is hypertrophied widened myocytes
- Systemic hypertension can cause:
o No symptoms
o Ischemic heart disease through hypertension amplifying atherosclerosis
o Kidney damage
o Stroke
o Progressive heart failure
o Sudden cardiac death
Pulmonary (right-sided) hypertensive heart disease
- Aka cor pulmonale, when right hypertrophy is isolated and not caused by left hypertrophy
- Normally, the right heart is thinner and more compliant than the left heart, due to pulmonary vessels having lower pressure
- Cor pulmonale is caused by pressure overload of the right ventricle, which causes right ventricular hypertrophy, dilation, possibly heart failure o The pressure overload is usually caused by a lung problem or pulmonary hypertension
- Acute cor pulmonale can follow a massive pulmonary embolism
o Will show right ventricle dilation without hypertrophy
o Right ventricle goes from crescent shape to oval
- Chronic cor pulmonale is secondary to prolonged pressure overload
o Include right ventricle hypertrophy
o Normally, myocytes are haphazardly arranged, but cur polmonale causes them to be arranged in a circle
Valvular heart disease
- Will be noticed due to stenosis, regurgitation, and/or incompetence
- Stenosis – failure of a valve to open completely
- Insufficiency – failure of a valve to close completely, allowing reversed flow
- Stenosis and insufficiency can happen at the same time
- Functional regurgitation – valve can’t close right because of a support structure
o Ex: dilation can pull papillary muscles in a way to prevent proper closure
- Pregnancy can make valve disease worse
- Page 561
- Valvular stenosis leads to pressure overload of the heart
o Can lead to high pressure “jets” of blood through the stenosis that hurts the endocardium after it
o Always a chronic problem, and few disorders can cause it
- Valvular insufficiency leads to volume overload of the heart (more volume in the chamber its backtracking into)
o Many disorders can cause valvular insufficiency
o Can be acute or chronic
- Acquired cases of valve disease are 2/3 of cases of valve disease - Most common causes of valve lesions are:
o Aortic valve stenosis from dystrophic calcification
o Ascending aorta insufficiency from dilation
o Mitral stenosis from rheumatic heart disease
o Mitral insufficiency from mitral valve prolapse (aka myxomatous degeneration)
Aortic stenosis from calcification:
- Acquired aortic stenosis from dystrophic calcification is the most common of all valve problems
- Usually a product of age related wear and tear on the aortic valve
- Atherosclerosis may be involved in calcification of valves
o Valve calcification differs from atherosclerosis in that the abnormal valves don’t accumulate smooth muscle, and instead have cells similar to osteoblasts, that make bone matrix proteins and promote deposition of calcium salts
- Congenital bicuspid (2 leaflet) aortic valves are usually more affected than the tricuspid (3 leaflet) valves
o Normally, the aortic valve has 3 leaflets (tricuspid), but a congenital anomaly can cause it to have 2 (bicuspid)
o The 2 leaflet valves have to handle more stress, so are more affected
- The calcium deposits prevent opening of the cusps
- Calcification begins in the fibrosa of the aortic valve
- Calcified aortic valves subject the ventricles to increasing pressure overload over time
- Commissural fusion is not seen (unlike in rheumatic aortic stenosis)
- Mitral valve will be normal in aortic stenosis (unlike in rheumatic aortic stenosis)
- The obstruction caused in calcific aortic stenosis will slowly narrow, which increases the pressure across the valve, causing the left ventricle pressure to increase and cause hypertrophy
o The hypertrophied myocardium is usually ischemic, and angina pectoris may occur
- Main symptoms of aortic calcification are angina, heart failure, or syncope
- Medical therapy works well in asymptomatic patients, while patients with symptoms need surgery - Bicuspid aortic valve is the most common congenital heart malformation in people
o It’s usually asymptomatic until later in life, then it causes aortic stenosis or regurgitation, endocarditis, and aortic dilation or dissection
o Bicuspid aortic valves are prone to calcification
o Cause ½ of cases of aortic stenosis in adults
o Usually the 2 cusps will be of unequal size, with the bigger one having a midline raphe
. The raphe is a major site of calcification
Mitral annular calcification:
- Calcium deposits can develop in the peripheral fibrous ring of the mitral valve, called the annulus
- They’re stony hard nodules behind the leaflets
- Usually won’t cause problems, but sometimes can cause regurgitation, stenosis, or arrhythmia
- Calcific nodules also are good sites for a thrombus to form and embolize
Mitral valve prolapse (aka myxomatous degeneration of the mitral valve)
- One or both mitral valve leaflets are “floppy” & prolapse back into the left atrium during systole
- The histological changes are called myxomatous degeneration
- The affected leaflets are often enlarged and thick
o The spongiosa layer thickens
- Secondary changes the prolapse causes:
o Fibrous thickening of the valve leaflets
o Fibrous thickening of the left heart endocardium, from long cords rubbing against it
o Thrombus on the atrial surface of the leaflets, or atrial walls
o Calcifications at the base of the posterior mitral leaflet
- Sometimes, Marfan syndrome can cause a mitral valve prolapse
o Mutation to fibrillin-1 changes the ECM, and increases TGF-β - Most people with a mitral valve prolapse are asymptomatic, and the condition is discovered by a midsystolic click during physical exam (floppy, so it claps and clicks)
- A minority of people with mitral valve prolapse can develop:
o Infective endocarditis
o Mitral valve insufficiency
o Stroke
o Arrhythmia
- Risk of problems is low in young, asymptomatic people, and higher in older people with symptoms
- Page 564
Rheumatic fever and rheumatic heart disease:
- Rheumatic fever is an acute, multisystem inflammatory disease that occurs within six weeks of an episode of strep pharyngitis
o Antibodies against M proteins from the strep, and T cells for the strep, can also target the heart
- Acute rheumatic carditis is commonly seen during rheumatic fever, and can progress over time into chronic rheumatic heart disease
- Main problem in rheumatic heart disease is valve problems
o Usually there’s a fibrosis of the valve, especially the mitral valve
- Page 565
- During acute rheumatic fever, inflammatory lesions are common
o Lesions in the heart are called Aschoff bodies, and are made of T cells, with some plasma cells and macrophage called Anitschkow cells
. Anitsckow cells can aka caterpillar cells, because their wavy looking chromatin
- The inflammation and lesions can happen in any of the heart layers, causing pericarditis, myocarditis, or endocarditis
- Inflammation of the endocardium and left heart valves usually causes necrosis in the cusps
o The cusps will have vegetations called verrucae on top of them - Problems with the mitral valve in rheumatic fever are leaflet thickening, commissural fusion and shortening, and thickening and fusion of the tendinous cords
o Chronic rheumatic heart disease almost always involves the mitral valve
- Rheumatic heart disease only accounts for a small amount of calcific aortic stenosis
- The more stenosed the valve, the more dilated the left atrium gets, and can form thrombi that can embolize
- Rheumatic fever causes:
o Migratory polyarthritis of large joints – one large joint gets painful and swollen, then that stops and another large joint gets painful and swollen, etc.
o Endocarditis (aka pancarditis)
o Subcutaneous nodules
o Erythema of the skin
o Sydenham chorea – neurologic problem with involuntary, rapid movements
o Minor symptoms:
. Fever, arthralgia, elevated blood levels of acute phase reactants
- To diagnose, you use the Jones criteria, which says history of group A strep infection, with either 2 major symptoms, or 1 major and 2 minor symptoms
- Occurs more commonly in children
- Once you’ve had rheumatic fever, there is a good chance another kind of infection can reactivate the disease
- Unlike infective endocarditis, rheumatic heart disease is not direct infection of the heart, it’s just Ig against strep somewhere else in the body cross reacting with the heart
Infective Endocarditis – when a microbe invades the heart valves or mural endocardium
- Causes making of vegetations made of thrombotic debris and organism, that usually destroy the heart tissue
- Most cases are caused by bacterial infections
- Acute infective endocarditis involves a highly virulent organism that causes necrotic ulcers
o It’s difficult to cure with antibiotics, and usually requires surgery o Death can occur within days to weeks, despite treatment
- Subacute infective endocarditis involves a less virulent organism that causes deformed valves and less damage than acute
o Antibiotics often work
- Many heart problems can lead to this infection
o Includes mitral valve prolapse, calcific valvular stenosis, bicuspid aortic valve, etc.
- Most common organisms to cause infective endocarditis are strep. viridans, which is part of the normal flora of the oral cavity
- The hallmark of infective endocarditis is vegetations containing fibrin, inflammatory cells, and bacteria, on the heart valves
- The aortic and mitral valves are the most common sites of infection
- Emboli can be shed from the vegetations
o Because the vegetations contain organisms, the embolism can cause septic infarcts where they lodge
- Fever is consistently shown in infective endocarditis
o May also see fatigue, weight loss, and flu symptoms
- Symptoms show up within a week of infection
- Murmurs are usually there in a left sided infective endocarditis
- Page 568-569
Noninfected (sterile) vegetations
- Caused by nonbacterial thrombotic endocarditis, or Libman-Sacks endocarditis
- Nonbacterial thrombotic endocarditis
o There will be deposition of small, sterile (nonbacterial) thrombi on the leaflets of heart valves
o These vegetations aren’t invasive, and don’t trigger an inflammatory response
o Usually happens along with another clotting disorder
- Libman-Sacks disease (endocarditis of systemic lupus erythematosus (SLE)) o Happens in the mitral and tricuspid valves
o They’re sterile, warty, pink vegetations
. Consist of highly granular, fibrinous eosinophilic material
o Intense cases can cause fibrinoid necrosis of the valve
What the 4 forms of vegetative endocarditis look like – page 567
- Rheumatic heart disease – small, warty vegetations on lines of closure of valve leaflets
- Ineffective endocarditis – large irregular masses on valve cusps that can extend onto chordae
- Nonbacterial thrombotic endocarditis – small bland vegetations attached at the line of closure
- Libman-Sacks endocarditis – small or medium sized vegetations on either or both sides of the valve leaflets
Carcinoid heart disease - the heart symptoms of a carcinoid tumor in the body
- Usually involves the endocardium and valves of the right heart
- Symptoms of carcinoid syndrome include flushing of skin, cramps, nausea, vomiting, and diarrhea
- Half of patients with carcinoid syndrome will have cardiac lesions
o The lesions are plaque-like fibrous thickenings made of smooth muscle cells & collagen
- The most common heart problem in carcinoid syndrome is tricuspid valve insufficiency
Problems with artificial valves:
- 2 main types of artificial valves:
o Mechanical prostheses
o Tissue valves – usually a bioprostheses made of animal tissue on a prosthetic frame
- Clots can commonly form on the artificial valve, which is why patients with artificial valves have to take anticoagulants
- Infective endocarditis can occur after a valve replacement
- Structural deterioration and hemolysis can also occur
Cardiomyopathy - means heart muscle disease - Diseases of the myocardium usually cause problems in heart wall thickness and chamber size, along with mechanical or electrical dysfunction
- Primary cardiomyopathies are when the heart causes the problem, and secondary is when a systemic problem causes the cardiomyopathy in the heart
- 3 patterns of cardiomyopathy:
o Dilated cardiomyopathy
o Hypertrophic cardiomyopathy
o Restrictive cardiomyopathy
- Dilated cardiomyopathy (aka congestive cardiomyopathy) - cardiomyopathy with progressive heart dilation and systole (contraction) dysfunction, usually along with hypertrophy
o Heart will be enlarged from hypertrophy, and flabby from dilation
o Mural thrombi are common
o There may be valve regurgitation from the dilation
o Can be acquired or genetic:
. Genetic- autosomal dominant is most common
Can cause mitochondrial defects in oxidative phosphorylation & β- oxidation
X-linked cardiomyopathy affects dystrophin, a cell membrane protein that helps connect the internal skeleton to the ECM
. Myocarditis- myocarditis can progress into dilated cardiomyopathy
. Alcohol- alcohol abuse is strongly associated with causing dilated cardiomyopathy
Any toxin can cause toxic insult to hurt the heart
. Childbirth – called peripartum cardiomyopathy
Pregnancy-associated hypertension, volume overload, or nutrient deficiencies could cause it
o Dilated cardiomyopathy starts with shortness of breath and easy fatigue, especially on exertion, which are signs of heart failure . Later in the disease, they’ll have poor ejection fractions
. ¾ of patients will die within 5 years
. Often can present with mitral regurgitations or arrhythmia
- Arrhythmogenic right ventricular cardiomyopathy (aka arrhythmogenic right ventricular dysplasia)
o Autosomal dominant genetic disease that causes the right ventricle to fail, and rhythm problems, that can cause death
. Rhythm problems are usually tachycardia or fibrillation
o The right ventricle will be thinned with loss of myocytes, and have lots of fat and fibrosis
o The major problem is a defect in cell adhesion proteins in desmosomes linking myocytes
- Hypertrophic cardiomyopathy – p. 572
o Heart will hypertrophy, the left ventricle will be less compliant and fill poorly, and there can be outflow obstructions
o Caused by a genetic problem with sarcomere proteins
o Usually causes problems in diastole, while systole will be fine
o The main morphologic feature of hypertrophic cardiomyopathy is massive heart hypertrophy, usually without ventricular dilation
o The ventricle can be compressed into a “banana” like shape
o The most common gene mutated is β-MHC
o The main problem in hypertrophic cardiomyopathy is decreased stroke volume, due to poor diastolic filling, due to decreased chamber size and poor compliance from the hypertrophied left ventricle
. Means dyspnea during exertion
o Sometimes, there will be a left ventricular outflow obstruction, causing a harsh systolic ejection murmur
o Angina often happens due to localized MI
o Can lead to fibrillation, arrhythmia, and clots
o It’s a very common cause in sudden, otherwise unexplained death of young athletes o Can treat with drugs that decrease heart rate and contractility, like β-blocker
o Clarification: hypertrophic CM is a mutation in sarcomere proteins, and dilated CM is a problem in cytoskeletal proteins
. DCM is a disease of abnormal force generation, while HCM is a disorder of energy transfer from mitochondria to sarcomeres
. Page 574
- Restrictive cardiomyopathy
o disorder of decreased ventricular compliance, causing impaired ventricular filling during diastole
. So systole is fine and normal, and diastole is the problem
o Ventricles will be about normal size, with no dilation, but the myocardium will be firm and noncompliant
. Atria are often dilated
o Other restrictive conditions:
. Endomyocardial fibrosis- disease in kids in tropical areas, that has fibrosis of both layers of the ventricle, making the ventricles less compliant
. Loeffler endomyocarditis- endomyocardial fibrosis with large mural thrombi
Differs from endomyocardial fibrosis in that there will be elevated blood eosinophils
Toxic things released by the eosinophils are thought to cause the inflammation, clot, and fibrosis
Often the patients have a problem with PDGFR genes
Treatment with tyrosine kinase inhibitors like imatinib can get rid of the endomyocarditis
. Endocardial fibroelastosis- involves fibroelastic thickening in the mural left ventricle in kids under 2, often with an aortic valve stenosis
- So dilated is problem in systole, hypertrophic is problem in diastole and hypertrophy, and restrictive is problem in diastole with no hypertrophy of ventricles (atria dilated)
o Arrhythmic is right heart failure with tachycardia or fibrillation o Dilated – the heart dilates and is too stretched to eject blood well (systolic problem)
o Hypertrophic – the ventricle hypertrophies to the point where it can’t fill with blood well (diastolic problem) which decreases what’s pumped
o Restrictive – heart chamber doesn’t change in size, but it can’t expand when needed because it isn’t compliant enough to fill (diastolic problem)
- Myocarditis - term for many disorders where infectious organisms and/or inflammatory processes hurt the heart
o Viral infections are the most common cause
o Chagas disease – endemic in S. America that is caused by a protozoa that causes myocarditis (trypanosome cruzei)
o Lyme disease can cause myocarditis
. Caused by a bacterial spirochete called Borrelia burgdorferi
. Usually will cause a heart conduction problem
o Myocarditis can also be caused by hypersensitivity rxns, especially to drugs, and autoimmune disorders
o Most often, myocarditis will show inflammatory cell infiltration, leading to myocyte necrosis
. Hypersensitivity myocarditis will include eosinophils in the infiltrate
o Can have many symptoms, spanning from asymptomatic to heart failure or arrhythmia
o Page 579
- Other causes of myocardial disease:
o Cardiotoxic drugs:
. Cancer therapy like chemotherapeutics, including tyrosine kinase inhibitors, can hurt the heart
Most common chemotherapeutics to hurt the heart are anthracyclines doxorubicin and daunorubicin
. Common findings in drug caused heart problems are myofiber swelling, fatty change, and cytoplasmic vacuolization
o Catecholamines . A pheochromocytoma is a tumor that enhances catecholamine release
. Excess catecholamines can cause heart necrosis
. Excess endogenous dopamine can hurt the heart
. Takotsubo cardiomyopathy – sudden, intense emotional or physical stress can cause acute left ventricle problems due to myocardial stunning (aka broken heart syndrome – from scrubs!)
. Cocaine can cause heart damage through catecholoamines o Amyloidosis - caused by deposition of insoluble fibrillar deposits in the heart
The deposits often form β-pleated sheets
. Can happen along with systemic amyloidosis, or just in the heart
. Senile cardiac amyloidosis- happens in older people, caused by deposition of transthyretin, which transports thyroxine
Has a better prognosis than systemic amyloidosis
. Cardiac amyloidosis usually causes a restrictive cardiomyopathy, but can also be asymoptomatic
. May see many semitranslucent nodules looking like drips of wax in the atria
. Eosinophilic amyloid deposits may be seen in the heart, and often form rings around myocytes and capillaries
. If there’s enough amyloid deposition, it can occlude vessels o Iron overload
. Can happen from hereditary hemochromatosis, or multiple blood transfusions through hemosiderosis
. The iron will interfere with systole
. Heart will be dilated and a rust-brown color
. You’ll see hemosiderin in myocytes, using a Prussian blue stain o Hyperthyroidism and hypothyroidism
. Heart problems are one of the first things you see in thyroid problems
. Hyperthyroidism will cause tachycardia, palpitations, and cardiomegaly . Hypothyroidism will cause decreased cardiac output due to decreased stroke volume and heart rate
Pericardial disease
- The most important pericardial disorders cause fluid accumulation, inflammation, fibrous constriction, or a combo of these 3
- Pericardial disease usually happens along with another heart disease or systemic disease
o Isolated pericardial disease is rare
- Pericardial effusion and hemopericardium
o Pericardial effusion- serous fluid filling the parietal pericardium
o Hemopericardium – blood filling the parietal pericardium
o Purulent pericarditis – pus filling the parietal pericardium
o With long standing pressure or volume overload, the pericardium dilates, allowing an effusion to get bigger without affecting heart function
o So chronic effusions don’t cause problems
o Rapid, acute effusions from hemopericardium during an MI or aortic dissection, can compress the heart, restricting cardiac filling, causing a cardiac tamponade
- Pericarditis- pericardial inflammation
o Most are acute, but some can be chronic
o Acute pericarditis
. Serous pericarditis – serous fluid
Usually caused by noninfectious inflammatory diseases like rheumatic fever, but can be caused by infections too
. Fibrinous and serofibrinous pericarditis
Most common types of pericarditis
Serous fluid mixes with a fibrinous exudate
Fibrinous pericarditis can cause a loud pericardial friction rub
. Purulent (suppurative) pericarditis Microbes invade the pericardial space
o They get there through direct extension from neighboring infections, seeding from the blood, lymphatic extension, or during a cardiotomy
The exudate can be thin, cloudy, and full of pus
Usually scars, and can cause constrictive pericarditis
. Hemorrhagic pericarditis
Exudate is made of blood mixed with fibrinous or suppurative effusion
Usually caused by a tumor spreading to the pericardial space
. Caseous pericarditis
Rare pericarditis from tuberculosis
Usually leads to chronic pericarditis
o Chronic pericarditis
. Adhesive pericarditis- stringy fibrosis that obliterates the pericardial sac, but doesn’t affect heart function
. Adhesive mediastinopericarditis- same as above, but this one puts a strain on the heart function
Can have an increased workload, causing hypertrophy and dilation
. Constrictive pericarditis- the heart is encased in a dense, fibrous or fibrocalcific scar that limits diastolic expansion and cardiac output
The scar prevents hypertrophy or dilation
Heart sounds are muffled
Heart can’t increase cardiac output when needed
- Rheumatic diseases causing heart disease
o Rheumatoid arthritis- mainly a disorder of joints
. Many chronic cases involve fibrinous pericarditis . Rheumatoid valvulitis- can cause fibrous thickening and calcification of the aortic valve
Heart Tumors
- Primary tumors of the heart are rare, it’s usually a metastatic tumor
- Primary heart tumors:
o Myxoma – benign tumor of the heart that’s the most common primary heart tumor
. Most happen in the atria, usually the right, at the fossa ovalis
. Can be mobile enough to cause occlusions during systole
. Hemorrhage and inflammation usually accompany it
. It’s caused by chromosome problems in multipotent mesenchymal cells
. Myxoma can be a familial syndrome called Carney Complex
The problem gene is PRKAR1
o Lipoma - benign tumor made of fat cells
. Can be asymptomatic, or obstruct valves, or cause arrhythmias
o Papillary fibroelastoma
. Benign neoplasm that can embolize
. Usually found on valves
. Made of connective tissue with lots of muccoploysaccharides and elastic fibers
o Rhabdomyoma
. Most common primary heart tumor in kids
. Usually noticed cause they are blocking a valve or heart chamber
. Often a cardiac rhabdomyoma is associated with tuberous sclerosis, caused by problems with TSC1 or TSC2 tumor suppressor genes
TSC proteins inhibit rapamycin (mTOR), which regulates cell growth and size
. Usually look small and gray-white, and there will be many there together
. They consist of weird looking myocytes called spider cells - Neoplasms not originally from the heart
o Most common are carcinomas of the lung and breast, melanomas, leukemias, and lymphomas
o Can cause effusions, or limit chamber filling
The major current limitation to the long-term success of cardiac transplantation is stenosing of coronary arteries
- Often patients with a transplanted heart are denervated, so they can’t feel an MI when it happens
- Over half of heart transplants live over 5 years