SBM2 Cardiovascular System 5 PDF

SBM2 Cardiovascul ar System 5 JENNIFER RAYBURN, M.D. MTSU PHYSICIAN ASSISTANT STUDIES  Objectives Analyze Analyze the types and pathophysiology of arteriosclerosis Question Question lipid classification and transport Criticize Criticize the details...

SBM2 Cardiovascul ar System 5 JENNIFER RAYBURN, M.D. MTSU PHYSICIAN ASSISTANT STUDIES  Objectives Analyze Analyze the types and pathophysiology of arteriosclerosis Question Question lipid classification and transport Criticize Criticize the details of the process of atherosclerosis Illustrate Illustrate the risk factors and clinical manifestations of atherosclerotic disease Apply Apply the risk factors and potential clinical manifestations of peripheral arterial disease Debate Debate the risk factors and potential clinical manifestations of arterial thrombus formation Apply Apply the types and potential clinical manifestations of embolic disease Contrast risk factors, pathophysiology, and clinical presentation of thromboangiitis Contrast obliterans, Raynaud phenomenon and Raynaud disease Distinguish Distinguish the etiology, pathophysiology, and classification of aneurysm and dissection  Terminology of Arteriosclerosis ▪ “Hardening of the arteries” ▪ Pathologic process that causes disease of the coronary, cerebral, and peripheral arteries ▪ Responsible for the majority of deaths in developed nations ▪ Can begin in childhood & advance with aging  Normal Arterial Wall ▪ Three layers: intima, media, & adventitia ▪ Intima: Closest to the arterial lumen (“intimate with blood”) ▪ Media: middle layer, thickest; mostly smooth muscle cells & extracellular matrix (contractile & elastic function of the vessel) ▪ Adventitia: Outer layer; contains nerves, lymphatics, and blood vessels (vasa vasorum) that nourish the cells of the arterial wall ▪ Endothelial cells: internal, single layer that covers the intima providing a biologically active barrier between the circulating blood and the vessel wall  Atherosclerotic Arterial Wall ▪ Key Components of the Atherosclerotic Inflammatory Process: ▪ 1. Endothelial cell dysfunction ▪ 2. Lipoprotein entry and modification ▪ 3. Leukocyte recruitment ▪ 4. Foam cell formation ▪ 5. Deposition of extracellular matrix  Stages of Plaque Development ▪ 1. Fatty Streak: represents the earliest visible lesions of atherosclerosis. Yellow discoloration on the arteries inner surface. Exist in the aorta and coronary arteries of most people by age 20. Do not cause symptoms and may regress over time. ▪ 2. Plaque Progression: Migration of smooth muscle cells from the media to the intima. Smooth muscle cells in the intima promote plaque progression by producing extracellular matrix that traps lipoprotein and adds bulk to the lesion. Lipid core is formed. ▪ 3. Plaque Disruption: Death of smooth muscle and foam cells over the years contributes to accumulation of lipids and cellular debris within the growing lipid core. Fibrous cap can rupture or erode over time  The Lipoprotein Transport System ▪ The lipoprotein transport system is essential for the transport of lipids (fats) through the bloodstream, as lipids are hydrophobic and cannot dissolve in plasma. ▪ Function of the Lipoprotein Transport System: 1. Regulates lipid metabolism and distribution. 2. Maintains lipid homeostasis and energy balance in the body.  Overview of the Lipoprotein Transport System ▪ Purpose: The lipoprotein transport system plays a crucial role in the transport of lipids (fats), including cholesterol and triglycerides, through the bloodstream. ▪ Lipoproteins: Lipoproteins are complexes made of lipids and proteins that enable the transport of hydrophobic lipid molecules in the water-based environment of the blood. ▪ They are classified based on their density: ▪ 1. Chylomicrons: Largest and least dense; transport dietary triglycerides and cholesterol from the intestines to other tissues. ▪ 2. Very Low-Density Lipoproteins (VLDL): Transport triglycerides and cholesterol from the liver to tissues. ▪ 3. Low-Density Lipoproteins (LDL): Often referred to as "bad cholesterol"; carry cholesterol to tissues, where it can be deposited in the walls of arteries or the liver. ▪ 4. High-Density Lipoproteins (HDL): Often called "good cholesterol"; involved in reverse cholesterol transport, carrying cholesterol away from the arteries and back to the liver for excretion or recycling. ▪ Key Functions of Lipoproteins: ▪ Energy Supply: Lipids are an essential source of energy for the body. ▪ Membrane Structure: Cholesterol is a critical component of cell membranes. ▪ Hormone Synthesis: Cholesterol serves as a precursor for steroid hormones.  The Lipoprotein Transport System ▪ Exogenous (Intestinal) System: ▪ Process: Starts with the absorption of dietary lipids in the intestines. ▪ Chylomicrons: Formed in the intestines, carry triglycerides and cholesterol through the lymphatic system and into the bloodstream. ▪ Lipoprotein Lipase (LPL): Enzyme that breaks down triglycerides in chylomicrons, releasing free fatty acids for tissue uptake ▪ Remnants: Chylomicron remnants are taken up by the liver for processing.  The Lipoprotein Transport System ▪ Endogenous (Hepatic) System: ▪ Process: Involves the liver producing VLDL to transport triglycerides and cholesterol. ▪ VLDL to LDL: As VLDL loses triglycerides through the action of LPL, it becomes Intermediate-Density Lipoprotein (IDL) and eventually LDL. ▪ LDL Uptake: LDL delivers cholesterol to cells or returns it to the liver. Excess LDL can lead to plaque formation in arteries ▪ Reverse Cholesterol Transport: ▪ HDL Formation: HDL is synthesized in the liver and intestines and circulates in the bloodstream, collecting cholesterol from tissues and other lipoproteins. ▪ Cholesterol Efflux: HDL transports cholesterol back to the liver for excretion via bile or recycling, thus reducing the risk of atherosclerosis.  Complications of Atherosclerosis ▪ Atherosclerotic plaques do not develop homogenously throughout the vasculature ▪ Typically, first develop in the dorsal aspect of the abdominal aorta and proximal coronary arteries, followed by the popliteal arteries, descending thoracic aorta, internal carotid arteries, and renal arteries. ▪ Complications of atherosclerotic plaques can include calcification, rupture, hemorrhage, and embolization Clinical sequelae of  Risk Factors for Atherosclerosis ▪ Non-modifiable: ▪ Advanced age ▪ Male sex ▪ Heredity (first degree relatives with CAD male190mg/dL or with known premature CAD  Hereditary Lipid Disorders: Others ▪ 2. Familial Combined Hyperlipidemia (FCH): ▪ Genetics: Polygenic disorder with multiple genetic and environmental factors involved. ▪ Lipid Profile: Elevated LDL cholesterol, triglycerides, or both, with normal to low HDL cholesterol. ▪ Clinical Features: Increased risk of CAD; often detected in adulthood. ▪ 3. Familial Hypertriglyceridemia: ▪ Genetics: Autosomal dominant disorder with mutations affecting triglyceride metabolism. ▪ Lipid Profile: Elevated triglycerides, often >500 mg/dL. ▪ Clinical Features: Increased risk of pancreatitis, hepatomegaly, and atherosclerosis; may also see eruptive xanthomas.  Hereditary Lipid Disorders: Others ▪ 4. Polygenic Hypercholesterolemia: ▪ Genetics: Multiple genes contribute to mildly elevated LDL cholesterol levels. ▪ Lipid Profile: Moderately elevated LDL cholesterol without a clear family history of hypercholesterolemia. ▪ Clinical Features: Increased risk of CAD, but typically later onset compared to FH. ▪ 5. Familial Dysbetalipoproteinemia: ▪ Genetics: Autosomal recessive disorder caused by mutations in the APOE gene, particularly the E2/E2 genotype. ▪ Lipid Profile: Elevated total cholesterol and triglycerides, with increased remnant lipoproteins (IDL). ▪ Clinical Features: Palmar xanthomas, tuberous xanthomas, and premature CAD. Hereditary Lipid Disorders: Diagnosis and Treatment ▪ Diagnosis: Have a Clinical Suspicion ▪ Lipid Panel: Screening includes measuring levels of LDL cholesterol, HDL cholesterol, total cholesterol, and triglycerides. ▪ Genetic Testing: Confirmatory genetic testing can identify specific mutations. ▪ Family History: Important for assessing the risk of hereditary lipid disorders. ▪ Management: ▪ Lifestyle Modifications: Diet, exercise, and weight management. ▪ Medications: Statins, PCSK9 inhibitors, fibrates, niacin, and other lipid- lowering agents. ▪ Regular Monitoring: Lipid levels and cardiovascular health should be regularly monitored.  Peripheral Vascular Disease ▪ Results from processes that can be grouped into three categories: ▪ 1. Structural changes in the vessel wall secondary to degenerative conditions, infection or inflammation ▪ 2. Narrowing of the vascular lumen by atherosclerosis, thrombosis, or inflammation ▪ 3. Spasm of vascular smooth muscle  Embolism vs. Thrombosis Embolism Thrombosis ▪ When material travels from one place in the body to another (piece of ▪ Thrombus is a solid clot that is a congregation of thrombus breaks free and reaches an platelets, fibrin, and clotting factors that form in artery with a small diameter and a vessel. lodges) ▪ Appear at sites of endothelial damage or ▪ Origin most often the heart (usually atherosclerotic stenoses, slow blood flow, or within bypass grafts (inciting event) resulting from disorders that cause intracardiac stasis of blood flow, such ▪ May cause abrupt cessation of blood supply to a as atrial fibrillation) particular organ causing acute arterial occlusion: pain, pallor, paralysis, paresthesia, or ▪ May originate from a thrombus or pulselessness (poikilothermia) atheromatous material overlying a ▪ Atheroembolism: condition of peripheral segment of the aorta. arterial occlusion by atheromatous material derived from more proximal vascular sites such ▪ Paradoxical embolus: If a venous as atherosclerotic lesions or aneurysms. Can occur spontaneously (50-60%) or from clot travels to the right heart procedures such as cardiac cath when chambers and is able to pass through atherosclerotic material is unintentionally an abnormal intracardiac dislodged from the proximal vasculature.  Thromboangiitis Obliterans (Buerger Disease) ▪ Non-atherosclerotic segmental inflammatory disease of small and medium sized arteries, veins, and nerves involving the distal vessels of the upper and lower extremities causing vaso-occlusive phenomena ▪ Most prevalent in India, Asia, and Middle East ▪ Strong association with cigarette smoking ▪ Young Men 20-45 yo; HLA-A9 & HLA-B5 ▪ Etiology: unknown, thought to be autoimmune ▪ Triad of symptoms: ▪ 1. Distal extremity ischemia both upper and lower extremities (claudication of calf or arch of foot, ischemic ulcers) ▪ 2. Raynaud phenomenon ▪ 3. Migrating superficial vein thrombophlebitis ▪ Diagnosis: Aortography is gold standard (will see “corkscrewing” of small collateral arteries around associated occlusions; Biopsy is definitive but rarely needed ▪ Treatment: smoking cessation (only definitive treatment)!! ▪ Other Treatment: Wound care with debridement of necrotic tissue ▪ Amputation if gangrene occurs; Iloprost (prostaglandin to help with critical limb ischemia)  Reynaud Phenomenon & Reynaud Disease ▪ Raynaud Disease: vasospastic disease of the digital arteries that occurs in susceptible people when exposed to cool temperatures or sometimes during emotional stress ▪ Extreme vasoconstrictor response that temporarily obliterates the vascular lumen, inhibiting blood flow. ▪ Triphasic color response: white (blood flow interrupted); cyanosis (accumulation of desaturated hemoglobin); and ruddy (blood flow resumes) ▪ May also have accompanying numbness, paresthesias, or pain of the affected digits ▪ Raynaud’s disease (Primary Raynaud phenomenon): isolated disorder; women between age 20-40 yo, symmetric disease in fingers and/or toes; benign ▪ Raynaud Phenomenon (Secondary Raynaud phenomenon or Syndrome): appears as a component of other conditions such as connective tissue diseases and arterial occlusive disorders, CTS, thoracic outlet syndrome, blood dyscrasias, drugs, etc. Develop after age 40 and may be asymmetric  The Aorta ▪ The largest conductance vessel in the vascular system ▪ Diameter is 3 cm at the base of the heart ▪ Ascending aorta is about 5-6 cm in length leads to the aortic arch from which rise three major vessels: brachiocephalic trunk, left common carotid artery, and left subclavian arteries ▪ Descending aorta continues beyond the arch with a narrowing diameter of about 2- 2.5 cm ▪ Once the aorta pierces the diaphragm, it becomes the abdominal aorta ▪ The aorta is subject to injury from mechanical trauma because it is continuously exposed to high pulsatile pressure and shear stress  Aortic Aneurysm ▪ Aneurysm is an abnormal localized dilation of an artery ▪ Diffuse ectasia: develops in older patients as elastic fiber fragments, smooth muscle cells decrease in number and acid mucopolysaccharide ground substance accumulates within the vessel wall (looks wavy) ▪ Aneurysm is when the diameter of a portion of the aorta has increased by at least 50% compared with normal ▪ True aneurysm: represents dilatation of all three layers of the aorta, creating a large bulge of the vessel wall ▪ 1. Fusiform aneurysm: more common; symmetrical dilation of the entire circumference of a segment of the aorta ▪ 2. Saccular aneurysm: localized outpouching involving only a portion of the circumference ▪ Pseudoaneurysm (false aneurysm): contained rupture of the vessel wall that develops when blood leaks out of the vessel lumen through a hole in the intima and medial layers and is contained by a layer of adventitia or perivascular organized thrombus. Very unstable and are prone to rupture completely Pseudoaneurysm  Aortic Aneurysm ▪ Risk Factors: Smoking, Age ▪ Clinical Presentation: >60 years, Caucasian, male, ▪ Most asymptomatic inherited genetic conditions, degenerative disorders of ▪ Symptomatic unruptured: connective tissue, infections, abdominal, flank, or back pain; vasculitis, aortic dissection, and abdominal bruit, pulsatile abdominal mass trauma ▪ Symptomatic Ruptured: abdominal, ▪ Inherited disorders typically flank, or back pain; hypotension or cause ascending thoracic syncope, flank ecchymosis aortic aneurysms ▪ Diagnosis: Often incidental finding on ▪ Atherosclerosis & it’s risk imaging studies. US, CT with iv contrast, MR imaging factors typically causes descending thoracic aortic and ▪ Screening, Treatment and Management abdominal aneurysms discussed in ClinMed Lecture  Aortic Dissection ▪ Life-threatening condition in which blood from the vessel lumen passes through a tear in the intima to the medial layer and spreads along the artery ▪ Any condition that interferes with the normal integrity of the elastic or muscular components of the medial layer can predispose to dissection (hypertension, aging, medial degeneration from genetic disorders), trauma ▪ Most common in sixth and seventh decades; more frequent in men. Two–thirds have history of hypertension. ▪ Ascending thoracic aorta (65%), descending thoracic aorta (20%), aortic arch (10%) and abdominal aorta (5%) ▪ Two categories (Stanford Class): Know These!!! ▪ 1. Type A dissection (proximal dissection): the ascending aorta and/or aortic arch is involved regardless of the site of primary tear ▪ 2. Type B dissection (distal dissection): does not involve the ascending aorta or arch. Confined to the descending thoracic aorta and abdominal aorta ▪ Two-thirds are Type A and one-third are Type B  Aortic Dissection ▪ Distinction between Type A and Type B is important because treatment strategies are different between the two types. ▪ Proximal involvement can be more devastating because of the potential for extension into the coronary and arch vessels, support structures of the aortic valve, or the pericardial space. ▪ Symptoms: sudden, severe pain with a “tearing” or “ripping” quality in the anterior chest (Type A) or between the scapulae (Type B), hypertension, difference between SBP in two arms (occlusion of subclavian arteries), neurologic deficits, early diastolic murmur, or cardiac tamponade ▪ Diagnosis: Cannot be delayed!! Contrast enhanced CT, Transesophageal ECHO, MRA or contrast angiography ▪ Treatment discussed in Clin Med Questions?????