Blood Flow and the Control of Blood Pressure Chapter 15 Blood Flow and the Control of Blood Pressure

About this Chapter How various blood vessels are constructed and role in circulation Components of "blood pressure", role and measurement Product exchange at the capillary beds Lymph vessels, distribution and role in circulation How blood pressure and circulation are regulated Key components of cardiovascular disease

The Blood Vessels and the Cardiovascular System Arteries: blood from heart Strong & Elastic Conduct blood to capillaries Sphincters Capillaries: exchange with cells Veins Return blood to heart Valves

The Blood Vessels and the Cardiovascular System Figure 15-1: Functional model of the cardiovascular system

Make Up of Blood Vessels: Arteries and Arterioles Endothelium Elastic tissues Rebounds Evens flow Smooth muscles Fibrous tissue Tough Resists stretch Figure 15-2: Blood vessels

Make Up of Blood Vessels: Veins and Venules (Contrasted to Arteries) Thinner walls Larger diameter Closer to skin Less muscle Less elastic Figure 15-3: Metarterioles

Angiogenesis: Growth of New Blood Vessels Normal body maturation and growth Endometrium Endurance training Abnormal growth to service cancerous tissue Wound repair and consequences Failure to regrow in heart tissues after heart attack Failure to regrow in brain after stroke

Blood Pressure: Generated by Ventricular Contraction Pulsatile: surges in arteries Elastic rebound evens & maintains pressure

Blood Pressure: Generated by Ventricular Contraction Figure 15-4: Elastic recoil in the arteries

Blood Pressure (BP): Measurements Systolic over diastolic About 120/80 mmHg Sphygmomanometer "Estimate of pressure" Korotkoff sounds

Blood Pressure (BP): Measurements Figure 15-7: Measurement of arterial blood pressure

More Blood Pressures: Pulse and Mean Arterial Pressures Pulse pressure = Systolic–Diastolic Mean arterial pressure (MAP) = Diastolic + 1/3 pulse pressure

More Blood Pressures: Pulse and Mean Arterial Pressures Figure 15-5: Pressure throughout the systemic circulation

Factors Controlling MAP : The Driving Pressure for Blood Flow Blood volume Cardiac output Resistance Distribution

Factors Controlling MAP : The Driving Pressure for Blood Flow Figure 15-10: Factors that influence mean arterial pressure

Antihypertensive Drug Classes: Action Sites Cardiac Output  Blood Pressure Total Peripheral Resistance = -Blockers Non-DHP CCBs Diuretics -Blockers ACE Inhibitors AT1 Blockers Direct renin inhibitors 1-Blockers 2-Agonists All CCBs Diuretics Sympatholytics Vasodilators Antihypertensive Drug Classes Antihypertensive Drug Classes: Action Sites β-Blockers decrease blood pressure primarily by reducing cardiac output. They also decrease renal renin output and, thereby, angiotensin II-mediated vasoconstriction. Angiotensin-converting enzyme inhibitors, angiotensin type-1 blockers, direct renin inhibitors, 1-blockers, 2-agonists, sympatholytics, and vasodilators decrease blood pressure by reducing total peripheral resistance through various mechanisms. Calcium channel blockers can either affect total peripheral resistance (dihydropyridines) or can reduce both cardiac output and total peripheral resistance (nondihydropyridines). Diuretics initially reduce cardiac output by decreasing intravascular fluid volume; with continued therapy, however, they also reduce total peripheral resistance via vasodilation. ACE = angiotensin-converting enzyme; AT1 = angiotensin type 1; CCBs = calcium channel blockers; DHP = dihydropyridine 16

Classes of Antihypertensive Drugs Aldosterone receptor antagonists (blockers) Angiotensin II antagonists Angiotensin-converting enzyme inhibitors -Blockers 1-Selective Nonselective -Blockers -1/-2 -1 predominant / Intrinsic sympathomimetic activity Calcium channel antagonists Nondihydropyridine Dihydropyridine Central 2 agonists Direct renin inhibitors Direct vasodilators Diuretics Thiazide-type Loop-type Potassium-sparing Ganglionic blockers Classes of Antihypertensive Drugs There are currently 11 classes and more than 200 different drugs or combinations of drugs approved by the United States Food and Drug Administration to treat hypertension. This slide outlines the different classes of antihypertensive drugs and highlights the major pharmacological differences among drugs within each class when there is important heterogeneity within the class. On average, most antihypertensive drugs decrease systolic and diastolic blood pressures by about 10 mm Hg and 5 mm Hg, respectively, when administered as monotherapy. 17

Distribution of Blood in the Body Organs Responds to metabolic need Precapillary sphincters Local & CNS regulators Huge variations (example: skeletal m 20-85%)

Distribution of Blood in the Body Organs Figure 15-13: Distribution of blood in the body at rest

Capillary Blood Flow: Greatest Total Cross Sectional Area Lowest Velocity Hydrostatic pressure drops Figure 15-17: The velocity of flow depends on the total cross-sectional area

Capillary Exchange: Colloidal Osmotic Pressure is Constant Proteins stay in capillary Water, oxygen, glucose – move out CO2, N wastes, water – move in Bulk flow out on arterial side, in on venous side

Capillary Exchange: Hydrostatic Pressure Declines High on arterial side – bulk flow out Low on venous side – bulk flow in Fenestrations &/or leaky joints speed exchange Figure 15-18a: Fluid exchange at the capillary

Net Out Flow Into ECF Net filtration – net absorption = net out flow About 2 L/day collected by lymph vessels Figure 15-18b: Fluid exchange at the capillary

Lymphatic System: Structure and Roles (overview) Lymphatic structures Capillaries with valves Lymph vessels Lymph nodes & organs Immune defense: lymphocytes Transport of fats Collects excess ECF Returns to plasma Edema

Lymphatic System: Structure and Roles (overview) Figure 15-19: The lymphatic system

Lymphatic System: Overview Consists of two semi-independent parts A meandering network of lymphatic vessels Lymphoid tissues and organs scattered throughout the body Returns interstitial fluid and leaked plasma proteins back to the blood Lymph – interstitial fluid once it has entered lymphatic vessels

Figure 20.2a

Lymphatic System: Overview Figure 20.1a

Lymphatic Vessels A one-way system in which lymph flows toward the heart Lymph vessels include: Microscopic, permeable, blind-ended capillaries Lymphatic collecting vessels Trunks and ducts

Lymphatic Capillaries Similar to blood capillaries, with modifications Remarkably permeable Loosely joined endothelial minivalves Withstand interstitial pressure and remain open The minivalves function as one-way gates that: Allow interstitial fluid to enter lymph capillaries Do not allow lymph to escape from the capillaries

Lymphatic Capillaries During inflammation, lymph capillaries can absorb: Cell debris Pathogens Cancer cells Cells in the lymph nodes: Cleanse and “examine” this debris Lacteals – specialized lymph capillaries present in intestinal mucosa Absorb digested fat and deliver chyle to the blood

Lymphatic Trunks Lymph is delivered into one of two large trunks Right lymphatic duct – drains the right upper arm and the right side of the head and thorax Thoracic duct – arises from the cisterna chyli and drains the rest of the body

Lymph Transport The lymphatic system lacks an organ that acts as a pump Vessels are low-pressure conduits Uses the same methods as veins to propel lymph Pulsations of nearby arteries Contractions of smooth muscle in the walls of the lymphatics

Regulation of Blood Pressure and Heart Rate Medullary cardiac control center (Brainstem) Cardioacceleratory Center Cardioinhibitory Center Baroreceptor reflex Carotid Aortic Kidney: blood volume Hypothalamus & Cortex: stress, blushing, etc.

Regulation of Blood Pressure Figure 15-22: The baroreceptor reflex: the response to increased blood pressure

Cardiovascular Diseases: #1 killer Risk Factors: Smoking Obesity Diabetes Genes Diseases: Hypertension Stroke "Heart Attack"

Mechanism of Atherosclerosis LDL build up Plaque  Flow Rupture Clot Blocked flow Tissue death

How Atherosclerosis Develops We now understand that atherosclerosis is a chronic inflammation of arteries, which develops over decades in response to the biologic effects of risk factors. Atherogenesis begins as a qualitative change to intact endothelial cells; when subjected to oxidative, hemodynamic, or biochemical stimuli (from smoking, hypertension, or dyslipidemia) and inflammatory factors, they change their permeability to promote the entry and retention of blood-borne monocytes and cholesterol-containing LDL particles. Inflammation and biochemical modifications ensue, causing endothelial and smooth-muscle cells to proliferate, produce extracellular matrix molecules, and form a fibrous cap over the developing atheromatous plaque. Plaques lead to clinical symptoms by producing flow-limiting stenoses (causing stable angina) or by provoking thrombi that interrupt blood flow on either a temporary basis (causing unstable angina) or a permanent one (causing myocardial infarction). Physical disruption (rupture) of the plaque exposes procoagulant material within the core of the plaque to coagulation proteins and platelets, triggering clotting.

Mechanism of Atherosclerosis Figure 15-24: The development of atherosclerotic plaques

Mechanism of Atherosclerosis Figure 15-24: The development of atherosclerotic plaques

Summary Blood vessels, anatomy & role in circulation Measuring blood pressures, MAP & pulse pressure Role of resistance in BP and distribution of blood Autoregulation, baroreceptros, medullary cardiac control center and CNS regulation of blood pressure & distribution

Summary Hydrostatic & colloidal osmotic pressures direct bulk flow in capillary exchange by diffusion, fenestrations & leaky joints Role of lymphatic system to return excess ECF to plasma Atherosclerosis common to several cardiovascular diseases