Pathology of the Cardiovascular System B1-B15 Flashcards
B/1. Congenital heart disease
Epidemiology.
General consequences of congenital heart diseases, after successful intervention.
40% of deaths in hungary are attributed to heart disease.
About 1% of all newborns have some congenital heart disease. Severe ones can cause neonatal death and others can be sypmtom fee.
Most are caused by errors of embryogenesis in weeks 3-8. Vast majority are idiopathic. Trisomies 13, 18, and 21 commonly have them.
Most can be corrected by surgery.
Left to right shunts are the most common congenital heart disease. Most of them are caused by ventricular septal defects.
Teratology of Fallot is the most common cyanotic congenital heart disease. Blue baby syndrome.
- *Consequences of surviving and living with a cardiac malformation:
a) Surgery injures the endocardium and endocardial injures pre‐disposes to endocarditis.
b) Hypertrophy due to hemodynamic changes. Jet stream has to be taken into account, ischaemic heart disease and arrhythmias.
c) Arrhythmias.
d) Surgical scars do not grow with the baby. Therefore, subsequent surgeries may be necessary.**
Any congenital heart disease, most of which require surgery, will predispose that patient to lifelong increased risks of other heart diseases.
B/1. Congenital heart disease
Categories of congenital heart disease.
Left to right shunts
Right to left shunts
Obstruction, stenosis, atresia, coarctation
B/1. Congenital heart disease
Left to right shunts, pathologic progression with no intervention
Left to Right Shunts. Involve an initial phase, and then a reversed phase.
- Shifts oxygenated blood from the left side to right.
- Does not initially cause hypoxia
- Volume overload of the RV
- The RV has to increase its force to meet increased demand
- Pulmonary edema
- In response to the edema,
- Acute: Pre-arteriolar muscles contract/spasm to decrease the edema
- Chronic: Endothelial lining thickens in response to the pressure/injury caused by it.
- These changes all further increase the pressure on the pulmonary system, until eventually the pulmonary system is actually higher pressure than the systemic.
- This causes Reversal of the shunt, and it the goes from Right to Left.
The point of reversal is called Eisenmenger Syndrome. It is irreversible. Cyanosis and death follow rapidly due to systemic perfusion with only deoxygenated blood.
B/1. Congenital heart disease
What are the causes of congeintal Left to Right shunts
Causes, in order of incidence: Ventricular septal defects, Atrial septal defects, and Patent Ductus Arteriosus.
1) Ventricular septal defects are the most common cause. Either from a pars membrana or pars muscularis defect.
- Membranous Vent. Septal defect
- Incomplete or Perforated Pars Muscularis.
2) Atrial septal defects then follow,
- 90% have incomplete septum secundum formation, leaving an open Ostium secundum. (ostium is higher, septum secundum forms on the right side, and is more firm)
- In the 10%, Septum primum does not finish forming, leaving an ossium primum, lower in the atria.
- Any Atrial septal defect smaller than 1cm does not require correction.
3) Patent Ductus Arteriosus
- The Ductus arteriosus may remain open if:
- There is not appropriate Prostaglanidin signaling after birth of the baby.
- There is Infant Respiratory Distress Syndrome, and the lungs are not yet ready, causing the pulmonary system pressure to remain very high even after birth.
- If patent ductus arteriosus is suspected, PGEs should be administered to initiate the muscle spasm that closes it.
- The high systemic pressure will cause a left to right shunt of blood via this patent ductus.
All of these 3 syndromes will cause elevated pulmonary pressure, RV hypertrophy, pulmonary edema, pulmonary arteriolar spasm, pulmonary intimal thickening, and eventual Eisenmenger sydrome, when the pressure becomes elevated beyond that of the systemic side, with a reversal of the shunt, then rapid cyanosis and death.
B/1. Congenital heart disease
Right to Left shunts, what are the physiologic consequences, compensations, and pathology.
Blue baby syndromes.
- Cause systemic hypoxia. De-oxygenated blood is being pumped systemically and bypassing the pulmonary circulation.
- Clubbing of the fingers and toes tips, (hypertrophy osteoarthropy also seen as a paraneoplastic syndrome)
- Polycythemia
- Paradoxical embolism
The body compensates for the hypoxia by RBC hyperproduction, aka polycythemia. This has the side effect of making the blood hyper-viscous, with an increased risk fro venous thrombosis. Due to the open Right-Left shunt, the venous thrombi that are generated can readily pass to the systemic arterial circulation, and generate paradoxical emboli.
B/1. Congenital heart disease
What are the causes of Right to Left shunts?
Causes, in order of incidence: Tetralogy of Fallot, Transposition of the Great arteries,
Tetralogy of Fallot is the most common cause.
- Ventricular Septal defect
- Pulmonary stenosis
- Dextrapositioning of the Aorta
- All of which cause, Right Ventricular hypertrophy
Transposition of the great arteries
- Spiral septal malformation causing separation of the two circulations, RV recieves and pumps all of the systemic blood, and the LV recieves and pumps all of the pulmonary blood
- Without a co-presenting shunt, such as a Ventricular Septal Defect or Roger shunt this is incompatible with postnatal life. Even with these conditions emergency surgery is generally needed within the first few days/months of life.
- Roger shunt is when both the ductus arteriousus and foramen ovale are still open. These shunts are generally only stable for a few days and need surgery as soon as possible.
Patent Truncus arteriosus. Rare in general, but common in DiGeorge syndrome, A large deletion of chromosome 22.
- There is no septal formation between the Pulmonary Artery and the Aorta, and they share a common trunk
- Thus both systems are recieving mixed blood.
- Cyanosis and
- RV hypertrophy
B/1. Congenital heart disease
What are the types of congential obstructions?
What are the types and consequences of Aortic coarctations?
Types: Pulmonary valve stenosis, Aortic valve stenosis, Aortic valve Atresia, and Aortic Coarctation (tube narrowing, may be before or after ductus arteriosus).
Aortic coarctations:
- Congenital coarctations: Usually Before the ductus arteriosis, and are compensated for by a patent ducuts arteriosus. Even with this alternate route, surgery is absolutely required very soon after birth.
Pre-ductal coarctation with patent ductus arteriosus: Presents early in life as cyanosis of the lower half of the body. Without surgery it fatal.
Post-ductal coarctation without a pda: Is usually asymptomatic for a very long time, until adulthood. Causes hypertension of the arms, neck, and head, and hypotension, coldness, and paleness of the lower half of the body.
The internal thoracic/epigastric artery anastomosis is often enlarged in these adults to help compensate and increase lower body flow.
Surgeries can easily fix these problems usually once they are diagnosed.
B/2. Myocardial infarction, sudden cardiac death
Too big son, look at the written notes.
B/2. Myocardial infarction, sudden cardiac death
Sudden cardiac death
What is it, what causes it
Sudden death from cardiac causes, no symptoms or death occuring within 24 hours of the first symptom.
Usually occurs in the elderly or obese from chronic ischemic heart disease, with at least one occlusive plaque (75%), which generates an arrythmia or AMI and arrythmia.
It can occur in young, healthy individuals from:
- an undaignosed heart malformation
- an undiagnosed arrythmia, usually from a conduction abnormality.
- a viral infection
- a hereditary cardiomyopathy
B/2. Myocardial infarction, sudden cardiac death
What are frequencies of occlusion of the different coronary arteries?
- The Left Anterior Descending, aka Left Anterior Interventricular is the most frequent. Accounting for about half of all AMIs. 40-50%
- 30-40% RCA
- 20-25% Left Circumflex artery
B/3. Angina pectoris, chronic ischaemic heart disease
Describe the types and causes of angina pectoralis
Angina pectoris: A transient, reversible ischemia of the heart, <10 minutes. No necrosis, causes the angina chest pain
- Stable angina: Caused by fixed coronary blockage greater that 70%. Causes predictable angina at a level of exertioin or emotional stress. Involves ST depress (ischemia with no necrosis). Responds well to nitrates. Dilates the coronaries (in large doses), and the peripheral vessels (occurs first even at small doses, decreasing the demand on the heart while also increasing the supply.
- Prinzmetal angina: Coronary muscle spasm, with or without a plaque contributing to the obstruction. Occurs at a random time and can occur at rest, often occurs during sleep. Responds very well and immediately to nitrates and muscle relaxants (according to Patho department, according to the pathophys department)
- Unstable or Crescendo angina: Increasing pain and pain frequency, caused by less and less exertion. Caused by an ruptured or fissured atherosclerotic plaque, which is releasing cholesterin plaques from its core. Causing micro-embolism of the corronary small arteries, and can also move to the brain and cause Transient Ischemic Attacks. Is not resolved by nitrates. The ruptured plaque will also be a thrombogenic site, and may produce thromboembolii as well creating the blockages, or it may progress to an occlusion at the plaque site causing an AMI. Unstable angina is thus a warning of a much more serious AMI and needs to be treated.
B/3. Angina pectoris, chronic ischaemic heart disease
Chronic ischemic heart disease
The patient has ischemia but not severe enough to cause angina or AMI. Causing chronic hypoxia of the myocardium.
Causes of CIHD
- After an AMI, the loss of contribution by the infarcted, dead myocytes has to be compenstaed for by the rest of the heart.
- The remaining heart muscle has increased workload
- Heart must hypertrophy to compensate
- Increased O2 demand
- Can’t be supplied because of the Coronary Heart Disease in the backround (which caused the AMI in the first place)
- Chronic ishemia
- Hypertesion.
- Generates hypertrophy
- Increased demand which is not met by coronary supply
- Low level Coronary Artery Disease
B/4. Rheumatic fever, non-infective endocarditis
Molecular causes of the cardiac symptoms of rheumatic fever.
It is a post-streptococcal disorder, occuring 2-4 weeks after infection of a group A beta-hemolysing infection. Involves multiple organs.
- Molecular mimicry of a S. pyogenes cell wall M-protein, for cardiac myosin. Causing the produciton of self antibodies and pancarditis, inflammation of all 3 heart layers.
- Endocarditis, and antibody reaction against the valves causes verruca formation. The verruca are non-infective, small vegetations on the valves, initiated by the antibody self reaction, composed mostly of fibrin and platelets due to clotting at the site of endocardial inflammation-induced damage.
- Myocarditis. Causes a Fibrinoid necrosis within the myocardium in the perivascular rgions. In the perivascular regions there are Aschoff bodies, Granuloma-like inflammations with lymphocytes, leukocytes, epitheloid cells, plasma cells, and macrophages
- Pericarditis. Which temporarily generates a fibrinous exudate, that generally resolves with no clinical problems.
- The pancarditis may cause arrythmias
- In severe cases it may cause enough dilation to cause mitral insufficiency, decreased pumping ability and Congestive Heart Failure.
- In rare cases, either the arryhtmia or CHF may be fatal in acute rheumatic fever but this is <1% of the time.
- Chronic rheumatic fever disease causes the chronically inflammed valves to become fibrotic and scarred, making them permanently shorter and less mobile. It als ocauses the thickening and shortening of the chorda tendinae.
- Generating a fish-mouth stenosis, which is both stenotic and insufficient.
- It affects the Mitral valve alone in 70% of cases, and affects both the Mitral and Aortic valves in 25%.
- Mitral stenosis causes left atiral hypertrophy and dilation, making it very amenable to thrombus generation
- Mitral insufficiency generates regurgitation during systole, causing LV eccentric hypertrophy and all of its problems.
B/4. Rheumatic fever, non-infective endocarditis
What are the non-cardiac symptoms of rheumatic fever and what are their causes?
Acute Rheumatic fever symptoms: ~80% occur in children, and the main symptoms is carditis. ~20% in adults. See the Jones criteria acronyms at the bottom.
- Fever
- Migratory poly-arthritis
- Nodule formation under the skin. Subcutaneous nodules
- Erythema marginatum - very large pink ring shaped rashes, with dark margins
- Syndenhams Chorea. St. Vitus’ dance
Immune complex mediated symptoms:
- Glomerulonephritis caused by immune complex deposition.
- Migratory polyarthritis
- Subcutaneous nodules
- Vasculitis anywhere in the body
Chronic symptoms:
Jones major criteria acronym
- Joints
- Obvious (cardiac symptoms
- Nodule
- Erythema marginatum
- Syndenham Chorea
OR, Jones criteria: is actually CANCER:
- Chorea
- Arthritis
- Nodules
- Carditis
- Erythema Marginatum
- Rheumatic Fever
B/4. Rheumatic fever, non-infective endocarditis
What are the diagnositc criteria for Rhemuatic fever?
The patient must have serological evidence of a previous group A streptococcal infection
Plus 2 of the Jones criteria (major criteria) or 1 major criteria and 2 minor manifestations.
Major criteria:
- Carditis
- Migratory polyarthritis
- Subcutaneous nodules
- Erythema marginatum
- Syndenham chorea
Minor criteria:
- Fever
- Arthralgia
- Elevated Acute Phase Proteins.
B/4. Rheumatic fever, non-infective endocarditis
List the non-infective endocarditis types (5)
Non-infective endocarditis:
- Non-bacterial thrombotic endocarditis
- Libman-Sacks endocarditis
- Carcinoid heart diesease
- Myxomatous mitral valve disease
- Calcifying aortic stenosis.
B/4. Rheumatic fever, non-infective endocarditis
Non-bacterial thrombotic endocarditis
- Occurs during hypercoagulable states
- Small thrombi develop onto the endocardium, producing small fibrinous/thrombocyte deposits.
- Does not damage or deform the valves.
- Lesions are sterile.
- In rare circumstances it can cause embolisms.
B/4. Rheumatic fever, non-infective endocarditis
Libman-Sacks endocarditis.
Libman-Sacks endocarditis:
- Sterile endocarditis related to
- Systemic Lupus Erythematosus or other immune complex diseases.
- Caused by complex deposition onto the edges of the valves, generating verucas
- It does cause inflammation, fibrinoid necrosis, and deformity of the valves.
- May produce serious deformities reminiscent of chronic rheumatic heart disease.
- The vegetations may occur anywhere in the heart, on the top or bottom of the valves, on the chorda tendinae, or on the endocardial surface of the atria/ventricle.
- Rarely, may cause embolism.
- Steroid management of SLE has decreased the prevalance of this
B/4. Rheumatic fever, non-infective endocarditis
Carcinoid heart disease
Carcinoid disease: a specific paraneoplastic syndrome caused by a tumor that secretes vasoactive compounds : serotonin, kallekrien, bradykinin, histamine.
Symptoms of carcinoid disease:
- Skin flushing
- Diarrhea
- Dyspnea and Bronchoconstriction
- Dermatitis
- Carcinoid heart disease
Carcinoid heart disease
- occur in 50% of carcinoid disease patients
- Affects mostly the Right Heart more than the left, since it recieves the highest concentration of the compounds.
- Shiny, White plaquelike thickenings on the endocardial surface.
- Composed of smooth muscle cells embedded in a mucopolysaccharide-rich matrix.
- It may produce tricuspid insufficiency or pulmonic stenosis.
B/4. Rheumatic fever, non-infective endocarditis
Myxomatous mitral valve disease
B/4. Rheumatic fever, non-infective endocarditis
Calcifying Aortic Stenosis
B/4. Rheumatic fever, non-infective endocarditis
Prosthetic Cardiac Valves
Two main types: Mechanical valves and Bioprosthetic valves
Mechanical valves:
- Require chronic anticoagulant treatment
- May cause significant RBC hemolysis from physical damage
- Very durable
- Infections occur at the suture lines.
Bioprosthetic valves:
- Made of human or porcine tissue
- Less durable
- Valve leaflets almost invariable undergo some fibrosis and may eventually cause stenosis.
- Calcification is very common and contributes to stenosis defelopment.
Both types:
- Are very susceptible to infections
B/5. Infective endocarditis
Describe acute endocarditis
Is a very serious infection that requires prompt intervention. It is the Microbial invasion and infection the heart valves and/or myocardium. It is divided into Acute endocarditis and Subacute endocarditis. Both are fatal if not treated.
- Often causes destruction of the underlying heart tissue
- Generates bulky, friable/crumbly vegetations.
- Composed of necrotic debris, fibrin and platelet thrombus, and infective micrboes.
- Infection of the myocardial layer can cause arrythmias and has a bad prognosis.
- A variety of organisms can cause it, the majority are extracellular bacteria.
Acute infectious endocarditis:
- Caused by highly virulent organisms
- Can infect previously healthy, undamaged endocardium/myocardium.
- Causes a rapid, strong fever, chills, weakness and fatigue.
- Murmurs are found in 90% of patients.
- Microemboli are generated and can cause:
- petechia
- Retinal hemorrhages
- Nail bed hemorrhages
- Erythemas around the fingers or palsm
- Depending on the microorganims, glomerulonephritis may occur from complex deposition. and may be severe enough to cause hematuria, albuminuria, renal failure.
- Substantial mortality even with good treatment.
B/5. Infective endocarditis
Describe Subacute infective endocarditis
Sub-actue infective endocarditis:
- Is caused by less virulent pathogens, and generally develops on already-diseased or scarred valves.
- Will often be asymptomatic for a long time, especially in the elderly.
- Symptoms are usually just mild, general flu-like symptoms.
- Most patients will recover, but requires several months of treatment
- If untreated it is fatal
- due to the progressive valve and myocardial damage, thrombus generation from the heart lesions, potential glomerulonephritis, arryhtmias, HF.
B/6. Valvular heart disease
What are the 4 categories of valvular heart disease?
List the disease that can cause valvular heart disease (6)
- Stenosis
- Insufficiency
- Vitium
- Murmur
Causes:
- Rheumatic feer
- Infective endocarditis
- Non-infective endocarditis
- Carcinoid disease
- Myxomatous Mitral Valve
- Calcific Aortic Stenosis
B/6. Valvular heart disease
Describe myxomatous valves
Myxomatous Degeneration:
- means the weakening of connective tissue
- involves accumulation of a mucinous ECM of dermatan sulfate glycosaminoglycans
Myomatous Mitral Valve: it is one of the most common valve disease
- A weakened valve, which can’t stay closed effectively.
- Involves a thinning of the fibrous middle layer of the valve and concommittant expansion of the spongious layer, from excessive mucoid ECM deposition.
- Weakness causes “balooning” valves when they are shut during systole.
- Usually affects the mitral valve first, then the triscuspid, then the aortic and pulmonic.
- “Floppy valves,” causing insufficiency and regurgitation
- Primary myxomatous valves are seen in syndromes with ECM deposition dysfucntion, like Marfan Syndrome.
- Can also be caused secondarily in any situation causing valve regurgitation.
B/6. Valvular heart disease
Describe calcifying valve stenosis on non-synthetic valves (normal)
Calcifying stenosis occus at the Aortic Valve most often.
Calcified Aortic Stenosis:
- is the most common degenerative valve disease
- Results from wear and tear, age.
- This is the valvular counterpart to age-related atherosclerosis, thus, extremely common in old age.
Morphology
- Calcification forms on the middle and oustide border of the valves, ring around the valve edges.
- Causes stenosis, outflow obstruction
- LV concentric hypertrophy
- If an individual has congenital bicuspid aortic valves (instead of the normal tricuspid aortic valves), It can onset at a much earlier age than normal, by 40-50 years.
B/6. Valvular heart disease
Describe Calcifying valve disease on prosthetic valves
On biological prosthetic valves, calcification is very common
Causes stenosis due to calcification of the valve borders as well as shrotening and hardening of the valves, causing insufficiency.
Calcification/necrosis occurs at the suture lines of a mechanical prosthetic valve, and can cause it to rip/detach.
