cardiology4 Flashcards
Major ASCVD Risk Factors
Cigarette smoking. Hypertension. Low HDL-C:
Emerging Risk Factors
Hypertriglyceridemia. Apolipoprotein B 100 (Apo B). LDL particle number. LDL particle size/density (small dense LDL). Lipoprotein (a) [Lp(a)]. Markers of Inflammation (hsCRP). Homocysteine. Prothrombotic Factors. Subclinical Atherosclerosis
4 Major Statin Benefit Groups
- Individuals with known clinical ASCVD. 2. Individuals with LDL ≥ 190 mg/dl. 3. Individuals with diabetes (>40 yo and LDL>70). 4. Individuals (>40 yo, LDL>70) without ASCVD or diabetes who have an estimated 10-year ASCVD risk ≥ 7.5%
Major Recommendations for Statin Therapy for ASCVD Prevention
In those whose 10-year risk is 5-7.5% or when the decision is unclear, other factors may be used to enhance the treatment decision making: Family History of Premature ASCVD, LDL-C > 160 mg/dl, hsCRP ≥ 2 mg/dl, Coronary Calcium Score ≥ 300 Agatston units or ≥ 75th percentile for age, sex, ethnicity, Ankle-Brachial Index
Hypertriglyceridemia
Severe hypertriglyceridemia is associated with acute pancreatitis. Moderate hypertriglyceridemia is associated with ASCVD. Biologically plausible associated risk factor. But unclear whether triglyceride lowering is beneficia. Associated with insulin resistance, metabolic syndrome, type 2 diabetes. “Risk factor” for ASCVD
HDL-C
Biologic Plausibility: HDL “removes” cholesterol from periphery and HDL has antioxidant and anti-inflammatory effects. Epidemiology: Low HDL levels are associated with increased risk for ASCVD. High HDL levels are associated with a protective effect against ASCVD. Randomized Trials: No evidence to date that HDL raising reduces ASCVD related events/death
Atherosclerosis HLD and LDL
Atherosclerosis is a slow, complex process. Elevated atherogenic lipoproteins (primarily LDL-C) are a critical component in the development of atherosclerosis and the progression to acute events. Cholesterol lowering therapy especially with statin therapy is effective in preventing acute atherosclerotic events, both acutely and chronically. What specific lipid goals should be is still not entirely clear. The “jury is still out” on whether HDL raising or TG lowering are clinically beneficial over and beyond LDL lowering
LDL particles
pose a risk for cardiovascular disease when they invade the endothelium and become oxidized, since the oxidized forms are more easily retained by the proteoglycans. A complex set of biochemical reactions regulates the oxidation of LDL particles, chiefly stimulated by presence of necrotic cell debris and free radicals in the endothelium. Increasing concentrations of LDL particles are strongly associated with increasing amounts of atherosclerosis within the walls of arteries over time, eventually resulting in sudden plaque ruptures and triggering clots within the artery opening, or a narrowing or closing of the opening, i.e. cardiovascular disease, stroke, and other vascular disease complications. LDL particles (though far different from cholesterol per se) are sometimes referred to as bad cholesterol because they can transport their content of fat molecules into artery walls, attract macrophages, and thus drive atherosclerosis. In contrast, HDL particles (though far different from cholesterol per se) are often called good cholesterol or healthy cholesterol because they can remove fat molecules from macrophages in the wall of arteries.
How Do Inflammation and Atherogenesis Overlap?
Subintimal LDL activates the endothelium. Activated leukocytes localize to sites of endothelial injury and initiate local inflammation. Intensified inflammation promotes plaque growth and eventual instability. LDL penetrates endothelium and is retained in the intima, where it undergoes oxidative modification. Proinflammatory lipids released from LDL stimulate endothelial cells to express adhesion molecules. Circulating monocytes adhere to endothelial cells expressing VCAM-1 and other adhesion molecules respond to chemokines (eg MCP-1) and migrate into the intima. Microphages begin taking up oxLDL and cholesterol accumulates in the cell, which develops into a lipid-laden foam cells and release proinflammatory mediators.
Why is Inflammation Implicated in Atherogenesis?
Evolution of host response to bacterial infection increases risk of sterile inflammation. Pathogen-associated molecular patterns (PAMPs). Danger-associated molecular patterns (DAMPs), such as Oxidized LDL and Cholesterol crystals
Monocytes
innate immune system leukocytes (2-10% of all leukocytes). Differentiate into tissue macrophages. Monocyte accumulation in atherogenesis is progressive and proportional to extent of disease. Monocyte adhesion to activated endothelium is an obligate step in atherogenesis. Inhibiting monocyte adhesion limits atherosclerosis initiation, such as VLA-4 and beta 2 integrins.
VLA-4
responsible for monocyte tight adhesion to VCAM-1. Knockout limits atherogenesis
ß2 integrins
include CD11a/CD18, CD11b/CD18, CD11c/CD18, CD11d/CD18. Knockout of all 4 CD18 integrins. Specific knockout of CD11c
Adaptive Immunity in Atherogenesis
Dendritic cell antigen presentation with subsequent T cell activation promotes clonal T cell expansion. Th1 response promotes IFN-gamma elaboration and atherosclerosis. TH17 cells may promote plaque instability and neoangiogenesis. Elaborate IL-17A, IL-22, and IL-21. Blockade of IL-17A may reduce atherosclerosis.
Inflammation and Atherogenesis: Summary
Immune response to injury initiates atherogenesis. Innate immune cell interaction with endothelium drives initial plaque formation. T cells promote further lesion expansion and plaque vulnerability.
T lymphocytes in Atherosclerosis
The major class of T lymphocytes present in atherosclerotic lesions is CD4+. In response to the local milieu of cytokines, CD4+ cells differentiate into the Th1 or Th2 lineage. Among the principal inducers of the Th1 and Th2 cells are interleukin (IL)-12 and IL-10, respectively. Activated T lymphocytes are functionally defined by the cytokines produced with interferon (IFN)-γ secreted from the Th1 cells and IL-4 from the Th2 cells. Much of the emphasis in atherosclerosis research in relation to T lymphocytes has focused on the role of Th1-type responses. The evidence for the role of Th1 cells includes the detection of IFN-γ mRNA and protein in lesions. A direct role in the disease process has been defined in atherosclerotic-susceptible mice that are deficient in either IFN-γ receptors7 or the cytokine itself. Conversely, injection of IFN-γ or the IFN-γ–releasing factors IL-12 and IL-18 enhances the extent of disease in apolipoprotein E −/− mice.
Progression of Atherosclerosis
After establishment of fatty streak, inflammatory mediators drive additional plaque expansion. Th1 mediated process in conjunction with macrophage apoptosis. Plaque growth transitions from stable plaque to unstable/ruptured plaque. Interplay of atherosclerosis and thrombosis.
What are the Major Drivers of Plaque Instability?
Macrophage apoptosis and necrosis promotes a “necrotic core”. Matrix metalloproteinases degrade the fibrous cap. Intra-plaque hemorrhage further weakens core.
Plaque Progression and Vulnerability
Progression from atherosclerotic plaque to myocardial infarction involves: Lesion expansion, Macrophage apoptosis and necrosis, Weakening of fibrotic cap, and Eventual plaque rupture
Can a Biomarker of Inflammation Predict Cardiovascular Risk?
Inflammatory underpinning of atherogenesis suggests inflammatory markers may predict residual risk. Add additional prognostic information on top of standard risk factors.
C Reactive Protein
Pentraxin acute phase reactant is produced by hepatocytes. It is possibly also expressed by macrophages and smooth muscle cells. Binds to modified membranes, apoptotic cells, and lipoproteins. Activates classical complement pathway
Mechanisms of Accelerated Atherogenesis in Autoimmune Diseases
Increased monocyte/macrophage activation, which is a potential common mechanism underlying all IMIDs. Impaired endothelial vasodilator function. This is observed in rheumatoid arthritis. Proatherogenic Lipoproteins include pro-inflammatory HDL, which increases LDL oxidation, and observed in RA, psoriasis. Plaque instability. RA associated with similar extent of CAD, but increased plaque vulnerability
HDL
and its protein and lipid constituents help to inhibit oxidation, inflammation, activation of the endothelium, coagulation, and platelet aggregation. All these properties may contribute to the ability of HDL to protect from atherosclerosis, and it is not yet known which are the most important. In the stress response, serum amyloid A, which is one of the acute-phase proteins and an apolipoprotein, is under the stimulation of cytokines (IL-1, IL-6), and cortisol produced in the adrenal cortex and carried to the damaged tissue incorporated into HDL particles. At the inflammation site, it attracts and activates leukocytes. In chronic inflammations, its deposition in the tissues manifests itself as amyloidosis.
Inflammation and HDL Function
Endotoxemia alters HDL size and decreases reverse cholesterol transport capacity. In chronic inflammation, HDL may lose its anti-atherogenic functions or become pro-atherogenic. HDL cholesterol efflux capacity is inversely associated with carotid intima-media thickness and risk of coronary artery disease. Relationship remains significant even after adjusting for HDL level or levels of apolipoprotein A-I. Impaired HDL efflux associated with more severe psoriasis. Those with rheumatoid arthritis have a similar overall prevalence of vessel DAC and had significantly more vulnerable plaque in LAD.
Association of Psoriasis With CV Events
Multiple studies have shown an association between psoriasis and myocardial infarction. Highest HR in younger patients with severe disease. Potential confounding by higher prevalence of cardiovascular risk factors. Obesity, hypertension, smoking, diabetes, metabolic syndrome. Each risk factor associated with an increased prevalence OR of 1.5-2.0
Is TNF-alpha Inhibition Associated with Decreased CV Risk?
Observational studies in rheumatoid arthritis have suggested a potential benefit of TNF alpha inhibition in reducing cardiovascular mortality and incident myocardial infarction. Initial studies in psoriasis have also suggested a possible reduction in CV events among patients prescribed TNF alpha inhibitors. Potential residual confounding remains in all of these observational studies.
Epidemiology and risk factors of peripheral artery disease
Adult prevalence 10%-12%. 20% over the age 70 or younger patients with diabetes or smoking. Risk Factors: Diabetes (4-fold increased risk), Smoking (2-3 X), Lipids (2 X), and Hypertension (2X). PAD has 6-fold increased risk of CV death
Symptoms of peripheral artery disease
Intermittent Claudication: Cramp, calf fatigue with exercise, resolves with rest, Blood flow normal at rest, limited with exercise, and No symptoms at rest, onset only with exercise. Ischemic rest pain/ischemic ulcers: Pain in the distal foot or heel, worsened by leg elevation and improved by dependency, Distal, painful ulcers on toes or heel, Blood flow limited at rest and exercise, and Symptoms at rest and with exercise
Signs of peripheral artery disease
Decreased or absent pulses. Bruits (abdominal, femoral). Muscle atrophy. In severe PAD (critical leg ischemia): Pallor of feet with elevation and Dependent rubor
Claudication Pathophysiology and Implications for Therapy
Prevent CV events (MI, stroke, vascular death). Improve limb symptoms, exercise performance and QOL. Heal ulcers and prevent limb loss. Treatments: Surgery or angioplasty improves hemodynamics, Exercise training improves muscle metabolism, and Drugs (cilostazol) have multiple mechanisms
Mechanisms of Aneurysm Formation
aneurysm formation is characterized by destruction of elastin and collagen in the media and adventia, loss of medial smooth muscle cells with thinning of the vessel wall, and transmural infiltration of lymphocytes and macrophages. Atherosclerosis is a common underlying feature of aneurysms. However, atherosclerosis is not the primary driving factor in the development of AAAs. Atherosclerosis is a disease that is widespread throughout the vasculature, however aneurysms only form in specific locations and only in certain individuals. Additionally, atherosclerosis is primarily a disease of the intima, while aneurysm formation primarily affects the media and adventitia. Currently there are thought to be four mechanisms relevant to AAA formation including: 1) proteolytic degradation of aortic wall connective tissue, 2) inflammation and immune responses, 3) biochemical wall stress, and 4) molecular genetics. Inflammation is driven by b and t lymphocytes, macrophages, cytokines, and autoantigens. Proteolytic enzymes such as MMP-2 and MMP-9 are upregulated while tissue inhibitor MMPs (TIMPs) are downregulated. uPa and tPa is also upregulated. Biomechanical stress causes elastin distribution, turbulent blood flow, and mural thrombus.
Epidemiology of AAA
Annual incidence estimated 40 to 50 per 100,000 men and 7 to 12 per 100,000 women. Accounts for approximately 16,000 deaths annually in U.S. Ruptured aneurysms are the 13th leading cause of death in US
Four major risk factors of aortic aneurysm
male gender, age, smoking, and family history
Abdominal Aortic Aneurysm Clinical Presentation
70% of patients are asymptomatic, then present with sudden death. 30% present with abdominal discomfort or severe pain radiating to the back, then die. Physician physical examination (rarely). Incidental discovery from imaging for another indication
Diagnosis of Abdominal Aortic Aneurysm
Plain X-ray, Ultrasound, Computerized tomography, Magnetic resonance imaging, and Arteriography (May miss it because angiography views the lumen not the arterial wall)
Computed Tomographic Imaging in diagnosing AAA
High resolution imaging of the aorta. Determines proximal and distal extent of AAA. Defines relationship of AAA to branch vessels. Planning for intervention
Aortic Dissection
Epidemiology ~ 30 cases / million / yr and account for 3-5 % sudden deaths. Untreated natural history: 1 % / hour mortality x 24 hours, 75 % mortality at 2 weeks, and 90 % mortality at 3 months
Aortic dissection mechanisms
1) primary intimal tear 2) rupture of vasa vasorum.
Aortic dissection risk factors
Hypertension (drugs e.g. cocaine), Inherited disorders of connective tissue (Marfan syndrome and Ehlers-Danlos syndrome), Bicuspid aortic valve, Coarctation, Pregnancy, Aortitis, Iatrogenic (surgery, arterial catheterization), and Trauma
Clinical manifestations of aortic dissection
Majority present with severe, tearing pain. Disruption of major arterial circulation leads to: Stroke (carotid), Syncope (vertebral), Myocardial infarction (coronaries), Intestinal ischemia (mesenteric vessels), and Renal failure (renal arteries)
Treatment of aortic dissection
Medical Rx includes Control of ΔPressure/ΔTime (Beta Blockade), Control of Blood Pressure (Nitroprusside, ACE inhibitors, and Calcium Channel Blockers) Control of Pain (Narcotic analgesia). Surgical Rx for Acute type A, Chronic type A with Aortic regurgitation, and Acute type B with: Rupture, Organ ischemia, and Marfans
Venous thromboembolic disease
3rd most common peripheral vascular disease. Nearly 2/3 of VTE are asymptomatic or undiagnosed. VTE account for 5%-10% of all hospital deaths. If no prophylaxis 24% of MI patients develop VTE, 60% of paralytic stroke patients develop VTE, and 75% of hip surgery patients develop VTE. 58% of PE deaths had not received any prophylaxis. Post-phlebitic syndrome in 40-80% of patients with VTE
Stages of chronic VTE
1) swelling, 2) visible collaterals, 3) stasis dermatitis, 4) ulceration.
Mechanisms of Thrombophilia
Thrombophilia caused by any alteration in coagulation balance that: increases thrombin production, enhances platelet activation/aggregation, mediates endothelial activation/damage, and/or mediates fibrinolytic inhibition
Thrombophilia Risk Factors
Severe inherited thrombophilia (homozygous protein C deficiency) is rare. Mild inherited thrombophilia (heterozygous Factor V Leiden) is common. Acquired thrombophilia is especially common in infection, inflammatory and certain drugs (estrogens).
Direct vs. Indirect Factor Xa Inhibitors
indirect Xa inhibitors (fondaparinux and idraparinux) are parenteral, require cofactor (AT), bind PF4, and inhibit free factor Xa only. Direct factor Xa inhibitor (rivaroxaban, apixaban, edoxaban) is taken orally, no cofactor need and is reversible, do not bind PF4 (no risk of HIT), inhibit free factor Xa and factor Xa in prothrombinase complex (better attenuation of thrombin generation).
Venous Thromboembolism
Risk factors include hypercoagulable states, venous trauma and stasis. Morbidity of acute venous and pulmonary thrombosis. Chronic risk for post phlebitic syndrome. Primary management is acute and chronic anticoagulation. Development of new anticoagulants
Apolipoprotein C2 or Apolipoprotein C-II
is a protein that in humans is encoded by the APOC2 gene. The protein encoded by this gene is secreted in plasma where it is a component of very low density lipoproteins and chylomicrons. This protein activates the enzyme lipoprotein lipase in capillaries, which hydrolyzes triglycerides and thus provides free fatty acids for cells.
Lipoprotein lipase (LPL)
is a member of the lipase gene family, which includes pancreatic lipase, hepatic lipase, and endothelial lipase. It is a water soluble enzyme that hydrolyzes triglycerides in lipoproteins, such as those found in chylomicrons and very low-density lipoproteins (VLDL), into two free fatty acids and one monoacylglycerol molecule. It is also involved in promoting the cellular uptake of chylomicron remnants, cholesterol-rich lipoproteins, and free fatty acids. LPL requires ApoC-II as a cofactor. LPL is attached to the luminal surface of endothelial cells in capillaries by heparen sulfated proteoglycans. It is most widely distributed in adipose, heart, and skeletal muscle tissue, as well as in lactating mammary glands.
Stages of prevention
Primordial – prevention of the emergence or development of risk factors for disease. Primary – prevention actions taken before the development of disease. Secondary – prevention actions taken after the development of disease to halt its progress and subsequent complications. Tertiary – prevention actions taken to reduce disability from disease and minimize suffering from its effects
Therapeutic Rationale of Antiplatelet
Anti-platelets prevent platelet adhesion to the site of a ruptured plaque, reduce platelet activation, and prevent platelet aggregation
Aspirin
Reduces platelet activation by blocking cyclooxygenase and thromboxane A2 (a vasoconstrictor) production. Aspirin blocks cyclooxygenase (prostaglandin H synthase), the enzyme that mediates the first step in the biosynthesis of prostaglandins and thromboxanes (including TxA2) from arachidonic acid.
Thienopyridines
(clopidogrel, ticlodipine, prasugrel, and ticagrelor). Inhibits adenosine diphosphate (ADP) production and platelet aggregation. The P2Y12 receptor blockers, thienopyridines clopidogrel, ticlopidine, prasugreland cyclopentyltriazolopyrimidine ticagrelorblock the binding of ADP to a platelet receptor P2Y12, thereby inhibiting activation of the GP IIb/IIIa complex and platelet aggregation.
Anti-GP IIb/IIIa antibodies and receptor antagonists
inhibit the final common pathway of platelet aggregation (the cross-bridging of platelets by fibrinogen binding to the GP IIb/IIIa receptor) and may also prevent adhesion to the vessel wall.
Class I antiplatelet guidelines
Aspirin 75-162mg daily for all CAD patients. Thienopyridines in all patients with ACS or PCI for one year following the event, in addition to aspirin 81-325mg. For post-bypass surgery patients, aspirin 100-325mg for at least one year. For post-stroke patients, aspirin alone (75-235mg), clopidogrel alone (75mg), or combined aspirin/dipyridamole (25mg/200mg) daily chronically. For symptomatic (not asymptomatic) peripheral arterial disease patients, aspirin alone (75-235mg) or clopidogrel alone (75mg). If the patient requires warfarin for another indication (e.g. AF), then continue low-dose aspirin 75-81mg and monitor closely for bleeding
Beta-blockers
reduce myocardial oxygen demand. Reduces heart rate. Reduces contractility. Reduces conduction velocity. Reduces systemic blood pressure
Class I beta-blocker guidelines
Beta-blockers in all with LVSD (ejection fraction
Class IIa beta-blocker guidelines
Beta-blockers in all with LVSD (ejection fraction
RAAS blockade
has multiple effects on the CV system. Vasodilation, Natriuresis, Decreased sympathetic activity, and Reduces cardiac remodeling. RAAS inhibition reduces mortality among post-MI patients, especially diabetics and LVSD
Class I RAAS inhibition guidelines
ACEIs: All with LVSD (ejection fraction 5.0 mEq/L)
2014 Class I blood pressure control guidelines
Age
Non-statin lipid treatments
are also available, but most have no evidence of efficacy. Bile-acid binding agents. Niacin. Fibrates
Smoking
promotes atherosclerosis and cardiac outcomes. Oxidizes LDL, Inflammatory, Decreases HDL, Causes endothelial dysfunction and reductions in NO. Smoking hurts, and cessation helps
Early Cardiogenesis
Male and female gametes fuse -> Fertilization. The unicellular zygote goes through a series of cleavages resulting in an increased number of cells -> morula. Morula -> transforms into a blastocyst
Blastocyst
Blastocyst has 3 components: Outer cell mass = trophoblast. Inner cell mass = embryoblast. Central cavity = blastocyst cavity
Embryoblast
the inner cell mass (abbreviated ICM and also known as the embryoblast or pluriblast, the latter term being applicable to all mammals) is the mass of cells inside the primordial embryo that will eventually give rise to the definitive structures of the fetus. The embryoblast has 2 layers: External layer = epiblast and Internal layer = hypoblast. These layers form a flat disc = Embryonic disc
Precardiac Cells
At the blastocyst stage, the precardiac cells are located within the epiblast on either side of the primitive streak. Epiblast cells migrate through the primitive streak -> giving rise to the intraembryonic mesoderm.
Gastrula
the single-layered blastula is reorganized into a trilaminar (“three-layered”) structure known as the gastrula. These three germ layers are known as the ectoderm, mesoderm, and endoderm. The precardiac cells are located within the mesoderm. The precardiac cells then migrate cephalically.
Development of the cardiogenic region
In the splanchnopleuric mesenchyme on either side of the neural plate, a horseshoe-shaped area develops as the cardiogenic region. This has formed from cardiac myoblasts and blood islands as forerunners of blood cells and vessels.
Development of endocardial tube
The cardiogenic cells migrate so that they are now ventral to the forebrain and foregut. The cardiogenic cells begin to form 2 endocardial tubes. By day 19, an endocardial tube begins to develop in each side of this region. These two tubes grow and by the third week have converged towards each other to merge together, using programmed cell death to form a single tube, the tubular heart. From splanchnopleuric mesenchyme, the cardiogenic region develops cranially and laterally to the neural plate. In this area, two separate angiogenic cell clusters form on either side and coalesce to form the endocardial tubes. As embryonic folding continues, the two endocardial tubes are pushed into the thoracic cavity, where they begin to fuse together, and this is completed at about 22 days
Morphologic Stages of heart development
DAY 21-22: Primitive heart tube is formed. The heart begins to beat on approximately DAY 22. The heart then goes through a looping process: Pre-loop, Loop, Post-loop (early and late) Septation begins at this stage
Pre-loop Stage
DAY 22. Straight heart tube. Atrioventricular Sulcus will become the intraventricular septum. The Primitive Ventricle is the primordium of the trabeculated portion of the LV. The proximal portion of the Bulbus Cordis is the primordium of the trabeculated portion of the RV. Blood flow begins.
Derivation of Cardiac Components
The inner layer of the heart tube is composed of an endothelial lining which will develop into the endocardium. The outer layer of the tube is derived from mesoderm (epimyocardium) and will go on to develop into myocardium and epicardium. Between the inner and outer layer is a substance called “cardiac jelly” which plays a role in the looping of the heart as well as septation.
Looping Stage
DAY 23-25. If the heart loops to the embryo’s Left it would be an L-loop and result in a malformed heart. The primitive atria rotate posteriorly. The long axis of the atrioventricular canal is initially cephalic to caudal, but with looping becomes posterior to anterior.
Early Post-Loop Stage
DAY 26-28. Note that the ventricles and atria are now in alignment. Septation begins. The ventricular septum is visible. The ventricles actually develop as outpouchings of the 2 areas visualized. At this stage the atria and ventricles are not entirely septated.
Truncus
Aortic and pulmonary valves. Ascending aorta. Pulmonary trunk
Conus
Infundibula of both ventricles
Bulbis Cordis
Trabeculated portion of the RV
Primitive Ventricle
Trabeculated portion of the LV
Blood Flow
DAY 25. Blood flow enters the heart tube through the sinus venosus via 3 sets of veins. 1) Umbilical vein- from the placenta (Disappears after birth). 2) The Vitelline vein- from the yolk sac. 3) The Cardinal vein-drains the embryo
The umbilical vein
is a vein present during fetal development that carries oxygenated blood from the placenta to the growing fetus. The unpaired umbilical vein carries oxygen and nutrient rich blood derived from fetal-maternal blood exchange at the chorionic villi. More than two-thirds of the blood enters the liver from its inferior border, while the remainder is shunted to the inferior vena cava through the ductus venosus, whence it returns to the fetal right atrium. Within a week of birth, the infant’s umbilical vein is completely obliterated and is replaced by a fibrous cord called the round ligament of the liver (also called ligamentum teres hepatis).
Vitelline Vein
are veins which drain blood from the yolk sac. The vitelline veins give rise to Hepatic veins, Inferior portion of Inferior vena cava, Portal vein, Superior mesenteric vein and contribute to the hepatic sinusoids.
Cardinal Vein
empty in the sinus venosus. Right becomes SVC, brachiocephalic vein, innominate veins. Left becomes Ligament of Marshall
Development of the Pulmonary Veins
Part of the splanchnic plexus forms the pulmonary venous plexus -> develops into the pulmonary veins. An endothelial projection from the LA connects to the pulmonary venous plexus and forms a common pulmonary vein. A lumen forms and the common vein branches forming the right and left pulmonary veins.
Atrial and Ventricular Septation
Approximately DAYS 28-42 (Post-loop Stage). Abnormalities will result in septal defects: Atrial septal defects and ventricular septal defects respectively.
Great Artery Formation
Approximately DAYS 35-56. Starting closest to the heart: Septation of the Conus, Septation of the Truncus
Septation of the Conus.
In the early post-loop stage, masses appear on the inside wall of the conus. Dextrodorsal and sinistroventral conal crests. The conal crests fuse with the ventricular septum caudally
Septation of the Truncus
Masses appear in the truncus: Dextrosuperior and sinistroinferior truncal swellings. Right intercalated swelling -> noncoronary aortic cusp. Left intercalated swelling -> anterior pulmonary cusp
Spiral shape of septation
The aorticopulmonary septum originates as an extracardiac septum in the aortic sac. SVCC becomes continous with SITS and DDCC becomes continuous with DSTS. The septum of the aortic sac, truncus and conus is therefore spiral shaped. At the great artery level, the pulmoanry artery is posterior and to the left. At the semilunar valve level, the pulmonary valve is anterior and to the left. At the infundibular level, the pulmonary infundibulum is anterior and to the right of the aortic infundibulum.
Development of the Aortic Arches
Related to the development of the head and neck. During the 4th week of development the pharyngeal arches appear. As each arch appears, the aortic sac contributes a right and left branch. These connect with the right and left dorsal aortas to form 6 pairs of arteries called the aortic arches.
