1. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Disorders of Blood Flow and Blood Pressure

2. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Blood Vessel Structure and Function Walls of arteries and veins are composed of three layers Tunica externa-collagen fibers and nerve fibers Tunica media-smooth muscle cells and elastin Tunica intima-single layer of endothelial cells

3. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Anatomy of a Blood Vessel

4. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Endothelial Cells Maintenance of a selectively permeable barrier Regulation of thrombosis Modulation of blood flow and vascular activity Regulation of cell growth (smooth muscle) Regulation of inflammatory/immune responses Maintenance of the extracellular matrix involvement in lipoprotein metabolism

5. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Vascular Smooth Muscle Cells Produce vasoconstriction and vasodilation Supplied by vasomotor nerves of the of the sympathetic component of the autonomic nervous system (ANS)  norepinephrine  constriction Synthesis collagen and elastin Elaborate growth factors and cytokines Migrate into the intima and proliferate after vascular injury

6. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Disorders of Blood Flow and Blood Pressure Disorders of the arterial circulation Hyperlipidemia Atherosclerosis Vasculitis Arterial disease of the extremities Aneurysms and dissection Disorders of arterial blood pressure Disorders of venous circulation

7. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Hyperlipidemia Medical condition characterized by any or all lipid profiles and/or lipoproteins in the blood Primary – genetically based Secondary – result form diseases such as diabetes, thyroid, renal and liver disorders, Cushing syndrome, obesity, ETOH consumption, estrogen administration, and other drug-associated changes in lipid profiles Classified according to the type of lipid elevated Hypercholesterolemia, hypertriglyceridemia, combined hyperlipidemia

8. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Lipids Triglycerides Used in energy metabolism Phospholipids Important structural constituents of lipoproteins, blood clotting components, the myelin sheath, and cell membranes Cholesterol Chemical activity similar to other lipid substances Hyperlipidemia Elevated levels of one or all of the above

9. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Lipoproteins Large molecular complex of lipids combined with apoproteins Synthesized in the liver (VLDL, HDL) and small intestine (chylomicrons) LDL is the main carrier of cholesterol HDL participates in the reverse transport of cholesterol Apoproteins control the ultimate metabolic fate of the lipoproteins Activate lipolytic enzymes that facilitate removal of lipids from lipoproteins Used in endocytosis and metabolism of proteins

10. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Types of Lipoproteins, Classified by Densities Chylomicrons Very–low-density lipoprotein (VLDL) Carries large amounts of triglycerides Intermediate-density lipoprotein (IDL) Low-density lipoprotein (LDL) Main carrier of cholesterol High-density lipoprotein (HDL) 50% protein

11. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Density and Structure of Lipoprotein

12. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Hyperlipidemia: Etiological Factors Nutrition (high calorie diets) Genetics Medications (beta blockers, estrogen, protease inhibitors) Comorbid conditions and metabolic diseases: obesity, DM, hypothyroidism, nephrotic syndrome, obstructive liver disease

13. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Exogenous and Endogenous Pathways of Lipid Transport

14. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Diagnosis of Hyperlipidemia Complete lipid profile after an overnight fast

15. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Treatment of Hyperlipidemia Focuses on dietary and lifestyle interventions Pharmacotherapy if dietary/lifestyle changes ineffective Primary target is reduction of LDL <160mg/dL (no major risk factors for CHD) <130mg/dL (2 or more major risk factors for CHD) <100mg/dL (high risk factors: CHD, DM) <70mg/dL (very high risk factors: acute coronary syndrome)

16. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Pharmacotherapy for Hyperlipidemia ClassificationMechanism of Action HMG CoA reductase inhibitors (statins) Reduces or blocks the hepatic synthesis of cholesterol, anti-inflammatory effects  Chol, TGL and HDL  Risk for ACS and CVA Bile acid binding resinsBind and sequester cholesterol containing bile acids in the intestine Used as adjuncts to statins NiacinBlocks the synthesis and release of LDL by the liver  VLDL, IDL, LDL  HDL (by 15-35%) FibratesDecrease the synthesis of VLDL by the liver  TGL by 20-50%

17. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Atherosclerosis

18. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Atherosclerosis “hardening of the arteries” CVD remains the leading cause of death among US men and women Major complications include ischemic heart disease, stroke, peripheral vascular disease Insidious onset Fibrous plaques appear as early as the 3 rd decade of life

19. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Major Risk Factors for Atherosclerosis Hypercholesterolemia Cigarette smoking Hypertension Family history of premature CHD in a first-degree relative Age (men ≥45 years; women ≥55 years) HDL cholesterol <40 mg/dL CRP levels Homocysteine levels

20. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins CRP (C-Reactive Protein) Major risk factor marker Serum marker for systemic inflammation High-sensitivity CRP (hs-CRP) may be a better predictor of cardiovascular risk than lipids

21. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins hs-CRP Interpretation hs-CRP (mg/dL)Risk for cardiovascular events <1low 1-3moderate >3high

22. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Homocysteine Derived from dietary amino acids Metabolism requires adequate levels of folate, vitamins B 6, B 12 and riboflavin Associated with endothelial damage

23. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Mechanisms of Development of Atherosclerosis Types of Lesions Associated with Atherosclerosis Fatty streaks Thin, flat yellow intimal discolorations that progressively enlarge Fibrous atheromatous plaque The accumulation of intracellular and extracellular lipids, proliferation of vascular smooth muscle cells, and formation of scar tissue Complicated lesion Contains hemorrhage, ulceration, and scar tissue deposits

24. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Clinical Manifestations of Atherosclerosis Narrowing of the vessel and resulting ischemia and infarction (medium size vessels) Sudden vessel obstruction due to plaque hemorrhage or rupture Thrombosis and formation of emboli resulting from damage to the vessel endothelium Aneurysm formation due to weakening of the vessel wall Heart, brain, kidneys, lower extremities, and small intestine arteries are most frequently involved

25. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Major Complications of Atherosclerosis Ischemic heart disease Stroke Peripheral vascular disease

26. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Vasculitis group of vascular disorders that cause inflammatory injury and necrosis of the blood vessel wall may affect arteries, veins, capillaries Clinical manifestations typically include constitutional signs and symptoms of fever, myalgia, arhralgia and malaise Classified by vessel size Pathogenic mechanisms Invasion of the vascular wall by an infectious agent Immune-mediated inflammation

27. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Arterial Disease of the Extremities

28. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Peripheral Vascular Disease PVD results in the same sequellae as arterial disease affecting the heart and brain Ischemia Impaired function Tissue necrosis

29. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Atherosclerotic Occlusive Disease Most commonly seen in the arteries of the lower extremities Superficial femoral and popliteal arteries are the most commonly affected Seen mostly in advanced age “Arteriosclerosis obliterans” Risk factors: smoking, DM

30. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Clinical Manifestations Onset is insidious Primary symptom is intermittent claudication Calf pain (gastrocnemius muscle has highest O2 consumption of any muscle group in the leg) Atrophic changes of skin, SQ tissue, and muscles Popliteal pulses are weak or absent Can progress to ischemis pain at rest, ulceration and gangrene

31. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Diagnosis and Rx of Arterial Occlusive Disease Diagnosis Assessment of limbs for signs of chronic ischemia Palpation of peripheral pulses The ratio of ankle to arm SBP (<0.9 indicates occlusion) Doppler study, US Treatment Aimed at reducing risk and managing symptoms Anti-platelet agents Surgery

32. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Acute Arterial Occlusion Sudden event that interrupts arterial bloodflow Usually a result of a thrombus or embolus Less frequently, trauma or arterial spasm Thrombi often arise as a result of erosion or rupture of a fibrous plaque

33. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins The Seven “P”s of Acute Arterial Embolism 1. Pistol shot (acute onset) 2. Pallor 3. Polar (cold) 4. Pulselessness 5. Pain 6. Paresthesia 7. Paralysis

34. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Raynaud Phenomenon Functional disorder caused by intense vasospasm of the arteries and arterioles in the fingers and toes Seen in otherwise healthy young women Precipitated by exposure to cold or by strong emotions Idiopathic Change in skin color that progresses from pallor to cyanosis, a sense of cold and changes in sensory perception

35. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Aneurysms

36. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Aneurysms Abnormal localized dilation of a blood vessel Occur in arteries and veins Most common site aorta True aneurysm-aneurysm is bounded by a complete vessel wall Pseudoaneurysm-localized dissection or tear in the inner wall of an artery with formation of an extravascular hematoma

37. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Types of Aneurysm Berry Fusiform Saccular Dissecting

38. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Berry Aneurysm Consists of a small, spherical vessel dilation at a bifurcation Most often found in the circle of Willis in the brain circulation

39. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Fusiform Aneurysm Characterized by gradual and progressive enlargement of the aorta Most often found in the thoracic and abdominal aorta

40. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Saccular Aneurysm A true aneurysm that extends over part of the circumference of the vessel Appears “sac-like”

41. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Dissecting Aneurysm False aneurysm resulting from a tear in the intimal layer of the vessel A blood filled cavity between the layers If in aorta, it is a life-threatening condition

42. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Aortic Aneurysms Most common cause is atherosclerosis and degeneration of the vessel media Can occur in any part of aorta Ascending aorta Aortic arch Descending aorta Thoracoabdominal aorta Abdominal aorta

43. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Abdominal Aortic Aneurysms > 90% located below the renal artery and involve the bifurcation of the aorta and proximal end of the common iliac arteries Infrarenal aorta is normally 2 cm size Aneurysm is defined as a diameter of >3cm in size Most are asymptomatic Usually palpable > 4 cm Abdominal or back pain may be present

44. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Aortic Dissection Life-threatening condition Hemorrhage into the vessel wall with longitudinal tearing Most common in 40-60 year old age group Predisposing factors Hypertension Degeneration of the medial layer of the vessel wall

45. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Venous disease

46. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Venous Circulation Veins are low-pressure, thin-walled vessels that rely on skeletal muscle pump and changes in abdominal and intrathoracic pressure to return blood to the heart One way valves in large veins Limited contractility Decreased driving pressure

47. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Venous System in the Legs Saphenous veins Deep veins Communicating system which connects the deep and saphenous Valves prevent retrograde flow

48. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Venous Disease Produces congestion of the affected tissues Predisposes to clot formation Include: Varicose veins Chronic venous insufficiency Deep vein thrombosis

49. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Risk Factors Associated with Venous Stasis Bed rest Immobility Spinal cord injury Acute myocardial infarction Congestive heart failure Shock Venous obstruction

50. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Venous Insufficiency Deep vein thrombosis (DVT) Causes deformity of the valve leaflets Valvular incompetence Loss of unidirectional blood flow Combination of both conditions

51. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Venous Disease Produce congestion of the affected tissues Predispose to clot formation Include: Varicose veins Chronic venous insufficiency Deep vein thrombosis (causes deformity of the valve leaflets)

52. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Varicose Veins Contributing factors Long periods of standing Increased abdominal pressure Heavy lifting Pregnancy

53. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Risk Factors Associated with Venous Stasis Bed rest Immobility Spinal cord injury Acute myocardial infarction Congestive heart failure Shock Venous obstruction

54. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Venous Insufficiency Deep vein thrombosis (DVT) Causes deformity of the valve leaflets Valvular incompetence Loss of unidirectional blood flow Combination of both conditions

55. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Risk Factors for DVT (Virchow’s Triad) Venous stasis Hyperreactivity of blood coagulation Vascular trauma

56. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Arterial Blood Pressure Systolic pressure (highest pressure) < 120 Diastolic pressure (lowest pressure) < 80 Pulse pressure is the difference between the systolic and diastolic Reflects the pulsatile nature of arterial blood flow Rises when stroke volume is increased Falls when resistance to outflow is decreased Mean arterial pressure is the average pressure during contraction and relaxation Good indicator of tissue perfusion

57. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Factors Influencing Mean Arterial Blood Pressure Physical Blood volume and the elastic properties of the blood vessels Physiologic factors Cardiac output Peripheral vascular resistance

58. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Mechanisms of Blood Pressure Regulation Short-term regulation: corrects temporary imbalances in blood pressure Neural mechanisms Humoral mechanisms Long-term regulation: controls the daily, weekly, and monthly regulation of blood pressure Renal mechanism Regulation of extracellular fluid volume

59. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Short-term Regulation of BP Humoral mechanisms Renin-angiotensin-aldosterone system (RAAS)-central role in BP regulation Vasopressin (ADH) (released from pituitary) Epinephrine/norepinephrine (adrenal gland)

60. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Renin-Angiotensin-Aldosterone System (RAAS) Renin is synthesized and stored in the kidney Released in response to  sympathetic NS activity,  BP or extracellular fluid volume or sodium concentration Converts angiotensinogen to angiotensin I in the blood stream Angiotensin I is converted to angiotensin II in the small vessels of the lung Catalyzed by angiotensin converting enzyme (ACE) Angiotensin II functions in both short- and long-term control of BP Strong vasoconstrictor  PVR Increases sodium reabsorption in kidneys Stimulates secretion of aldosterone from the adrenal gland

61. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins RAAS Control of BP

62. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Humoral Mechanism: Vasopressin Antidiuretic hormone (ADH) Released from the pituitary Direct vasoconstrictor effect

63. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Short-term Regulation of BP Neural mechanisms ANS control of BP Reticular formation of the medulla and lower third of the pons contains the vasomotor and cardiac control centers “cardiovascular center” Parasympathetic impulses  vagus nerve  slowing of HR Sympathetic  spinal cord and peripheral nerves  increase in HR and cardiac contractility Intrinsic reflexes (inside the CV system) Baroreptors (walls of vessels and heart) Chemoreceptors (carotid bodies) Extrinsic reflexes (outside the CV system) Mediate BP responses associated with pain and fever

64. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Long Term Regulation of BP Regulation of extracellular fluid volume by the kidneys Regulates BP around an equilibrium point (normal BP for an individual) Too much extracellular fluid BP  Water and sodium excretion by kidneys  Too little extracellular fluid BP  Water and sodium excretion by kidneys rises 

65. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Hypertension Most common of all health problems in adults Leading risk factor for heart disease More common in: men than women until women reach menopause blacks than whites lower socioeconomic groups elderly Prevalence increases with age

66. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Categories of Hypertension Primary hypertension (essential hypertension) The chronic elevation in blood pressure that occurs without evidence of other disease 90 to 95% of all HTN Secondary hypertension The elevation of blood pressure that results from some other disorder, such as kidney disease Malignant hypertension An accelerated form of hypertension

67. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Classifications of Essential Hypertension Systolic/diastolic hypertension Both the systolic and diastolic pressures are elevated. Diastolic hypertension The diastolic pressure is selectively elevated. Systolic hypertension The systolic pressure is selectively elevated.

68. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Most Common Causes of Secondary Hypertension Kidney disease (renovascular hypertension) Adrenal cortical disorders Pheochromocytoma Coarctation of the aorta Sleep apnea

69. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Joint National Committee on Detection, Evaluation, and Treatment of Hypertension (JNC-8) Systolic pressure of less than 120 mm Hg and a diastolic pressure of less than 80 mm Hg are normal. Systolic pressures between 120 and 139 mm Hg and diastolic pressures between 80 and 89 mm Hg are considered prehypertensive. A diagnosis of hypertension is made if the systolic blood pressure is 140 mm Hg or higher and the diastolic blood pressure is 90 mm Hg or higher. For adults with diabetes mellitus, less than 130/80 mm Hg

70. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Target Organ Damage The heart Hypertrophy Brain Dementia and cognitive impairment Peripheral vascular Atherosclerosis Kidney Nephrosclerosis Retinal complications

71. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Goals of Treatment To achieve and maintain arterial BP below 140/90 In patients with DM or renal disease, below 130/80 Prevention of morbidity and mortality

72. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Treatment of HTN Lifestyle modification Weight management Regular physical activity Adopt the DASH diet Reduction of dietary sodium intake Limitation of alcohol Smoking cessation Pharmocotherapy Correct or control the diseases that are causing HTN

73. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Treatment of HTN-Pharmacotherapy Based on stage and severity of HTN The presence of target organ disease Existence of other disease conditions and risk factors

74. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Factors Affecting Treatment Strategies for Hypertension The person’s lifestyle Demographics Motivation for adhering to the drug regimen Other disease conditions and therapies Populations at risk for orthostatic hypotension (elderly, DM, ANS dysfunction) Potential for side effects Cost

75. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Drugs Used in the Treatment of Hypertension Diuretics β-adrenergic blocking drugs Angiotensin-converting enzyme (ACE) inhibitors Angiotensin II receptor blockers Calcium channel blocking drugs Central α 2 -adrenergic agonists α 1 -Adrenergic receptor blockers Vasodilators

76. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Hypertensive Crisis Accelerated, severe form of HTN Systolic pressure greater than 180 or diastolic pressure greater than 120 Hypertensive emergency When elevated BP is responsible for symptoms, signs, or laboratory evidence of end-organ damage (mental status changes, intracranial hemorrhage, retinopathy, aortic dissection, cardiac ischemia, CHF, acute renal failure Immediate and rigorous medical management

77. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Orthostatic Hypotension Definition An abnormal decrease in blood pressure on assumption of the upright position Causes Decrease in venous return to the heart due to pooling of blood in lower part of body Inadequate circulatory response to decreased cardiac output and a decrease in blood pressure

78. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Causes of Orthostatic Hypotension Condition that decreases vascular volume Dehydration Conditions that impair muscle pump function Bed rest Spinal cord injury

79. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Causes of Orthostatic Hypotension (cont.) Conditions that interfere with cardiovascular reflexes Medications Disorders of autonomic nervous system Effects of aging on baroreflex function

80. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Common Causes of Orthostatic Hypotension Related to Hypovolemia Excessive use of diuretics Excessive diaphoresis Loss of gastrointestinal fluids through vomiting and diarrhea Loss of fluid volume associated with prolonged bed rest

81. Copyright © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins Complaints Associated with Orthostatic Intolerance Dizziness Visual changes Head and neck discomfort Poor concentration while standing Palpitations Tremor, anxiety Presyncope, and in some cases syncope