Robbins: Vascular Diseases

• Cardiovascular diseases can be divided into diseases of blood vessels and the heart.
• Robbins 10th edition, chapter 10 discusses blood vessels.
• Robbins 10th edition, chapter 11 discusses the heart.

Vascular Diseases

• Vascular diseases are some of the most common and lethal conditions.
• Arterial and venous problems.
• Key issues includes narrowing or obstruction of the vessel and weakening of vessel walls.
• Narrowing or obstruction can be progressive, like atherosclerosis, or acute, like thrombosis or embolism.
• Weakening of vessel walls leads to vasodilation and/or rupture.

Blood Vessel Structure

• Arteries have cell and extracellular matrix layers, including endothelial cells (EC), lamina elastica, vascular smooth muscle cells (VSMC), and extracellular matrix (ECM, collagens).
• The intima, media, and adventitia are components of blood vessels.
• Vascular Smooth Muscle Cells (VSMC) participate in vascular repair, pathologies, vasoconstriction, and dilation.
• Endothelial Cells (EC) play an important role for normal blood supply.
• Large arteries have loss of elasticity with age and diseases like hypertension and diabetes.
• Medium-sized arteries go towards organs like the renal artery, controlling blood pressure.
• Small arteries have a thin wall and strongly reduced blood flow.
• Capillaries have a diameter smaller than red blood cells.
• Some vessels are "closed," like those forming the blood-brain barrier (BBB).
• Certain vessels feature sieves, called fenestrae, such as those of the liver and kidney.
• Thick-walled arteries consist of three layers and an internal elastic membrane (laminal elastica).
• Contraction of Vascular Smooth Muscle Cells (VSMC) regulates blood pressure in arteries.
• Thin-walled veins have an irregular and often bigger lumen.
• Veins contain either less or no vascular smooth muscle cells, and no elastica, resulting in no contraction.

Hypertension

• Sustained diastolic pressure is >90 mm Hg and/or systolic pressure >140 mm Hg.

• 140 mmHg leads to a high risk of atherosclerosis.

• Hypertension is usually asymptomatic for many years.
• Primary hypertension is mainly idiopathic, the cause is salt retention, stress, etc, and the belief that hypertension is helpful at all is not a helpful concept.
• Secondary hypertension results from renal or adrenal disorders.
• Malignant hypertension involves rapidly increasing BP in 1-2 years and causes death in 5% of hypertensive patients, with a diastolic pressure >120 mm Hg or systolic pressure >200mm H.
• Over 25% of the population has hypertension and has effects on blood vessels or organs, shear stress causes endothelial cell activation..
• Pathological effects include damage to blood vessels (thrombosis, atherosclerosis, aneurysm, dissections) and organs (heart, brain, kidney, eyes (retinopathy)).
• Degenerative changes in the vasculature with large and medium sized arteries are aortic dissection and cerebrovascular hemorrhage.
• Hyaline atherosclerosis is typical for mild hypertension, includes proteinaceous amorphous material(hyaline), and a narrow lumen.
• Hyperplastic arteriolosclerosis is typical for severe hypertension, and has 'onion-skinning' leading to luminal obliteration and consists of VSMC and thickened basement membrane.
• Intimal thickening is a typical and possibly reversible response to vascular injury.
• Physical trauma, hypertension, infections, inflammation, immune injury, toxic exposure, and aging can cause intimal thickening.
• Migration of VSMC to the intima leads to proliferation and ECM production.
• VSMC phenotype changes show higher proliferation and a higher extracellular matrix production capacity.

Aneurysms and Dissections

• Aneurysms are congenital or acquired dilations of the heart or blood vessels involving the entire wall thickness: intima, media, and adventitia.
• A dissection happens when blood enters the area between separate layers of the vessel wall.

Varicose Veins

• Varicose veins are abnormally dilated, tortuous veins due to a chronically increased pressure in the vein and a weakened vessel wall support.
• Superficial veins in legs (NL: spataderen) and esophageal varices in the throat.
• General risks include stasis, congestion, edema, pain, prone to thrombosis, ruptures and ulcerations.
• Esophageal varices are induced by portal hypertension (liver cirrhosis), leading to increased blood flow into upstream veins.
• A danger includes rupture that can lead to gastrointestinal bleeding and can be fatal.

Vasculitis

• Vasculitis is inflammation in the vessel wall.
• The cause is immune complex deposition in vascular wall and drug induced by eg penicillin-protein complex (often in skin) and virus induced eg Hepatitis B.
• An autoimmune disease is leads to inflammation in arteries.
• Thrombophlebitis & Phlebothrombosis "phlebo" means vein.
• Deep Venous Thrombosis (DVT) is a type of Thrombophlebitis & Phlebothrombosis and shows inflammation and prolonged immobilization.
• Causes of Prolonged immobilization are bed rest, long trips, congestive heart failure, pregnancy, oral contraceptive use, malignancies, obesity, gender (male) age (>50).
• distal edema results in superficial vein dilations, heat, redness, swelling and pain.
• A serious complication is pulmonary embolism.

Arteriosclerosis and Artherosclerosis

• Arteriosclerosis is the hardening of the small arteries, causing an arterial wall thickening and loss of elasticity in arterioles.
• Atherosclerosis is the most frequent and clinically important pattern, with plaque formation in the tunica intima of larger arteries.
• Plaque formation is intravascular accumulation of lipids(cholesterol, cholesterol esters), cellular debris.
• Macrophages covered by a fibrous cap cause obstruction of blood vessels.
• Low Density Lipoprotein (LDL) is bad cholesterol, and brings cholesterol into tissues.
• High density Lipoprotein (HDL), is good cholesterol and brings cholesterol from tissues to the liver.
• Apolipoproteins LDLs are produced by liver during disease, in plaque results in oxidized LDL.
• Risk of plaque rupture can lead to thrombosis and emboli.
• There is progressive, slow disorder in atherosclerosis with high morbidity and mortality (50%).
• Risk factors for atherosclerosis include genetics, increasing age an being male, and modifiable factors such as hyperlipidemia, hypertension, smoking, diabetes mellitus, metabolic syndrome, and inflammation.

Atherosclerosis Pathogenesis and Morphological Changes

• The first is endothelial Cells (EC) injury (A).
• Secondly there is Platelet adhesion (B).
• A Monocyte adhesion and migration to the intima (B) also helps form the plaque.
• Next is Accumulation of lipoproteins (B, C).
• Followed by Activation of macrophages, VSMC*) recruitment and transformation into foam cells (C, D), note that foam cells are macrophages, VSMC and loaded with lipids.
• Also is Lipid accumulation within macrophages (D), and Oxidized LDL and cholesterol crystals.
• Next is VSMC recruitment (C), followed by
• VSMC proliferation and ECM production (E).
• Foam cells: (lipid accumulation in macrophages) where
• VSMC = vascular smooth muscle cells.
• Fatty Streaks are the first lesion and occur at a young age.
• Atherosclerotic plaques consist of SMC+ fibrous tissue (hardly any lipids).
• Neovascularization and Calcification can also be signs.

Plaque Types

• Stable plaques narrow vessels causing ischemia.
• Unstable Plauques have a risk of acute plaque rupture, thrombosis or embolisation and are thin caps and have dense inflammatory infiltrates.

Heart Diseases Overview

• Heart diseases are the leading cause of mortality worldwide.
• The heart pumps 7500 l/day, the first organ that becomes active in uterine.
• Heart failure has 600.000 deaths/year in USA (#1), and is mostly idiopathic, but is with Angiotensin (AT) and Atrial Natriuretic Peptide (ANP).

Heart Failure

• Heart failure is a failure of the pump, and means output from the heart is insufficient to supply tissue with enough oxygen.
• Heart failure is usually with congestion of the venous circulation, congestive heart failure (CHF).
• This progressive condition has a poor prognosis and is often irreversible.
• At first shows no symptoms and later symptoms like fatigue, shortness of breath and edema.
• The body increases the muscular Heart and heart-rate, but ends with oxygen consumption by heart so collapse.

Cardiomyopathies

• Cardiac diseases include primary conditions, secondary ones as caused by other diseases and can be idiopathic as well.
• Two main clinical pathological patterns: dilated cardiomyopathy (90%) and hypertrophic cardiomyopathy.
• Dilated CM is most common and has enlargement of cardiac chambers and flabby heart wall.
• Dilated CM can be induced by doxorubicin (=anti-cancer drug).
• Hypertrophic Cardiomyopathy has a thick walled heart and the Myocard does not relax and has diastolic dysfunction.

Other Heart Conditions

• Endocarditis is inflammation in the endocardium: Microbial infection of heart valves (from oral cavity or skin, risk factors: catheders, artificial heart valves).
• Myocarditis is Infections in myocard: mostly viral infections (CMV, HIV, Influenza, 5% of patients with Lyme disease).
• Ischemic heart diseases manifest in several closely related syndromes caused by myocardial ischemia like is angina Pectoris (AP), myocardial infarction (MI), chronic IHD, or sudden cardiac death.
• The cause is 90% due to reduced coronary blood flow caused by obstructive atherosclerotic vascular disease in coronary arteries, and can causes by lack of oxygen in heart.

Angina vs MI

• Angina Pectoris involves intermittent chest pain which means transient ischemia, not severe enough and can be relieved by calcium blocker.
• Myocardial Infarction is when arterial blockage stops blood to flow and is heart attack that is nonrevisable.
• Morphology of Myocardial Infarction shows in inflammation which can be showed in a lab test.
• Diagnosis shows on leakage of enzymes from myocyte into serum such as Myoglobin.
• Also can show Creatine kinase myocardial isoform (CK-MB), Lactate dehydrogenase (LDH), and Troponin T and I.
• Kinetics can be used to estimate the timing of MI