Chapter 17 Guyton and hall

How does acetate and citrate affect blood flow?

Both cause mild degrees of vasodilation

What are some vasodilator agents (besides NO)?

Bradykinin Histamine (derived from mast cells in damaged tissues and basophils in blood)

What is the vasodilator theory?

The greater the rate of metabolism or the less the availability of oxygen or some other nutrients to a tissue, the greater the rate of formation of vasodilator substances in the tissue cells. The vasodilator substances then are believed to diffuse through the tissues to the precapillary sphincters, metarterioles, and arterioles to cause dilation.

What are some vasoconstrictor agents of humoral control?

- Norepinephrine (more important) or epinephrine (less important, can cause mild vasodilation) - Angiotensin II (important in constricting small arterioles to increase the TPR and decrease sodium and water excretion by kidneys) - Vasopressin (more powerful than angiotensin II; major function is to increase water reabsorption from the renal tubules back into the blood; could have large effects but is usually only secreted in minute amounts)

What does bradykinin do?

- Bradykinin causes both powerful arteriolar dilation and increased capillary permeability. - Kinins appear to play special roles in regulating blood flow and capillary leakage of fluids in inflamed tissues. - It also is believed that bradykinin plays a normal role to help regulate blood flow in the skin, as well as in the salivary and gastrointestinal glands.

What causes this acute auto-regulation mechanism?

1. Metabolic theory 2. Myogenic theory

How can NO be used to help erectile dysfunction?

A drug (e.g., sildenafil) that inhibits cGMP-specific phosphodiesterase-5 (PDE-5), an enzyme that degrades cGMP. By preventing the degradation of cGMP, the PDE-5 inhibitors effectively prolong the actions of NO to cause vasodilation can treat erectile dysfunction. Penile erection is caused by parasympathetic nerve impulses through the pelvic nerves to the penis, where the neurotransmitters acetylcholine and NO are released. By preventing the degradation of NO, the PDE-5 inhibitors enhance the dilation of the blood vessels in the penis and aid in erection,

What is endothelin?

A large 27-amino acid peptide that requires only minute amounts to cause powerful vasoconstriction. it is present in the endothelial cells of all or most blood vessels but greatly increases when the vessels are injured.

What are the two mechanisms of blood flow control?

Acute control and long term control

What are some vasodilator substances?

Adenosine (important for local control), carbon dioxide, adenosine phosphate compounds, histamine, potassium ions, and hydrogen ions.

What factors increase growth of new blood vessels?

Almost all are small peptides. - Vascular endothelial growth factor (VEGF) - Fibroblast growth factor - Platelet-derived growth factor (PDGF) - Angiogenin Oxygen stimulates the formation of these

What is the oxygen demand theory for local blood flow control?

Also known as the nutrient demand theory. Basically an increase in oxygen causes vasoconstriction, a decrease causes vasodilation.

How does carbon dioxide affect blood flow?

An increase causes moderate vasodilation in most tissues but marked vasodilation in the brain. Also, carbon dioxide in the blood, acting on the brain vasomotor center, has an extremely powerful indirect effect, transmitted through the sympathetic nervous vasoconstrictor system, to cause widespread vasoconstriction throughout the body.

What special mechanism for local blood flow occurs in the brain?

An increase of either hydrogen or carbon dioxide or both of these ions dilates the cerebral vessels and allows rapid washout of the excess carbon dioxide or hydrogen ions from the brain tissues.

What are the steps of angiogenesis?

Angiogenesis begins with new vessels sprouting from other small vessels. 1. The first step is dissolution of the basement membrane of the endothelial cells at the point of sprouting. 2. Rapid reproduction of new endothelial cells that stream outward through the vessel wall in extended cords directed toward the source of the angiogenic factor. 3. The cells in each cord continue to divide and rapidly fold over into a tube. 4. The tube connects with another tube budding from another donor vessel (another arteriole or venule) and forms a capillary loop through which blood begins to flow. 5. If the flow is great enough, smooth muscle cells eventually invade the wall, so some of the new vessels eventually grow to be new arterioles or venules or perhaps even larger vessels.

Which peptides can block the growth of new blood vessels?

Angiostatin (a fragment of the protein plasminogen) Endostatin (breakdown of collagen Type XVII)

Which disease can cause overall vasodilation?

Beriberi. The peripheral vascular blood flow increases twofold to threefold. Basically in this disease there is a deficiency of thiamine (vitamin B), niacin and riboflavin. This diminishes smooth muscle contractile ability and therefore causes local vasodilation.

What is a key mechanism in long-term local blood flow regulation?

Change the amount of vascularity of tissue.

What is humoral control of circulation?

Control by substances secreted or absorbed into the body fluids, such as hormones and locally produced factors.

What will lead to angiogenesis?

Decreased oxygen consumption (can lead to retrolental fibroplasia in premature babies who were at first given high doses of O2)

What is nitric oxide derived from?

Endothelial-derived nitric oxide synthase (eNOS) enzymes synthesize NO from arginine and oxygen and by reduction of inorganic nitrate.

What are some other nutrients that may have some control over local bood flow?

Glucose, amino acids, fatty acids (a lack of them causes vasodilation).

What is reactive hyperemia?

Increased blood flow to an organ in response to a period of reduced blood flow

What can histamine do?

Histamine has a powerful vasodilator effect on the arterioles and, like bradykinin, has the ability to increase greatly capillary porosity, allowing leakage of both fluid and plasma protein into the tissues. In many pathological conditions, the intense arteriolar dilation and increased capillary porosity produced by histamine cause tremendous quantities of fluid to leak out of the circulation into the tissues, inducing edema.

What is auto-regulation of blood flow?

How blood flow to an organ remains constant over a wide range of perfusion pressures. Between arterial pressures of about 70 mm Hg and 175 mm Hg the blood flow increases only 20 to 30% even though the arterial pressure increases 150%.

What effect can chronic hypertension or atherosclerosis have on NO synthesis?

Impaired NO synthesis may contribute to excessive vasoconstriction and worsening of the hypertension and endothelial damage, which, if untreated, may eventually cause vascular injury and damage to vulnerable tissues such as the heart, kidneys, and brain.

What is hypertrophic remodeling?

In larger arteries that do not constrict in response to the increased pressure, the vessel wall is exposed to increased wall tension that stimulates a hypertrophic remodeling response and an increase in the cross-sectional area of the vascular wall. The hypertrophic response increases the size of vascular smooth muscle cells and stimulates formation of additional extracellular matrix proteins, such as collagen and fibronectin, that reinforce the strength of the vascular wall to withstand the higher blood pressures. However, this hypertrophic response also makes the large blood vessels stiffer, which is a hallmark of chronic hypertension.

What is the metabolic theory of autoregulation?

In living active tissues substances that dilate blood vessels are accumulated. If blood flow through the tissue decreases - this causes stagnation of the vasodilating substances and leads to vasodilation which causes increase in the blood flow. As the blood flow increases the vasodilating substances are washed away and vasodilation decreases to normal.

What is outward remodeling and outward hypertrophic remodeling?

In patients with renal failure who undergo dialysis, an arteriovenous (A-V) fistula directly from the radial artery to the antecubital vein of the forearm is created to permit vascular access for dialysis. Blood flow rate in the radial artery may increase as much as 10 to 50 times the normal flow rate, depending on the patency of the fistula. As a result of the high flow rate and high shear stress on the vessel wall, the luminal diameter of the radial artery increases progressively (outward remodeling) while the thickness of the vessel wall may remain unchanged, resulting in an increase in cross-sectional area of the vascular wall. In contrast, wall thickness, lumen diameter, and the cross-sectional area of the vascular wall on the venous side of the fistula increase in response to increases in pressure and blood flow (outward hypertrophic remodeling).

What is inward eutrophic remodeling?

In small blood vessels that constrict in response to increased blood pressure, the vascular smooth muscle cells and endothelial cells gradually—over a period of several days or weeks—rearrange themselves around the smaller lumen diameter, a process called inward eutrophic remodeling, with no change in the total cross-sectional area of the vascular wall.

Where do some specific mechanisms of local blood flow occur?

In the kidneys, brain and skin.

What special mechanism for local blood flow occurs in the skin?

In the skin, blood flow control is closely linked to regulation of body temperature. Although skin blood flow is only about 3 ml/min/100 g of tissue in cool weather, when humans are exposed to heat, skin blood flow may increase up to 7 to 8 L/min for the entire body. When body temperature is reduced, skin blood flow decreases, falling to barely above zero at very low temperatures.

What is the myogenic theory of autoregulation?

In the tissues smooth muscles surrounding vessels contract in response to distention caused by elevation of the blood pressure. The tension is proportionate to the distending pressure. This tension can be described by the law of Laplace. T=P • r.

How does hydrogen affect blood flow?

Increase causes dilation of arterioles. Decrease causes arteriolar constriction.

How does magnesium affect blood flow?

Increase causes powerful vasodilation because it inhibits smooth muscle contraction

How does calcium affect blood flow?

Increase causes vasoconstriction because it stimulates smooth muscle contraction.

How does potassium affect blood flow?

Increase causes vasodilation because potassium can inhibit smooth muscle contraction.

What is active hyperemia?

Increasing blood flow of an organ when its metabolic activity increases. For example, active hyperemia in skeletal muscle can increase local muscle blood flow as much as 20-fold during intense exercise.

Which organs receive the largest percent of cardiac output?

Liver and kidneys

What determines vascularity?

Maximum blood flow need, not average need.

Can anything override the myogenic mechanism?

Metabolic factors appear to override the myogenic mechanism in circumstances in which the metabolic demands of the tissues are significantly increased, such as during vigorous muscle exercise, which can cause dramatic increases in skeletal muscle blood flow.

What does NO do?

NO activates soluble guanylate cyclases in vascular smooth muscle cells, resulting in conversion of cyclic guanosine triphosphate (cGTP) to cyclic guanosine monophosphate (cGMP) and activation of cGMP-dependent protein kinase (PKG), which has several actions that cause the blood vessels to relax. The released NO relaxes blood vessels and increases the diameters of the larger upstream blood vessels whenever microvascular blood flow increases downstream. Released not only from small arteries and arterioles but also larger vessels.

Is acute blood flow control enough to manage an increased arterial pressure?

No, It will only reduce flow back to about 10-15% above the original control value.

What is acute blood flow control control?

Rapid changes in local vasodilation or vasoconstriction of the arterioles, metarterioles, and precapillary sphincters that occur within seconds to minutes to provide very rapid maintenance of appropriate local tissue blood flow.

What are two other metabolic mechanisms for control of local blood flow?

Reactive hyperemia and active hyperemia

What is long term control of blood flow?

Slow, controlled changes in flow over a period of days, weeks, or even months. In general, these long-term changes provide even better control of the flow in proportion to the needs of the tissues. These changes come about as a result of an increase or decrease in the physical sizes and numbers of blood vessels supplying the tissues.

How is NO synthesis stimulated?

The flow of blood through the arteries and arterioles causes shear stress on the endothelial cells because of viscous drag of the blood against the vascular walls. This stress contorts the endothelial cells in the direction of flow and causes significant increase in NO release. Also by some vaso-constrictors such as angiotensin II

What is bradykinin?

The kinins are small polypeptides that are split away by proteolytic enzymes from α2-globulins in the plasma or tissue fluids. A proteolytic enzyme of particular importance for this purpose is kallikrein, which is present in the blood and tissue fluids in an inactive form. This inactive kallikrein is activated by maceration of the blood, tissue inflammation, or other similar chemical or physical effects on the blood or tissues. As kallikrein becomes activated, it acts immediately on α2-globulin to release a kinin called kallidin that is then converted by tissue enzymes into bradykinin. Once formed, bradykinin persists for only a few minutes because it is inactivated by the enzyme carboxypeptidase or by converting enzyme, the same enzyme that also plays an essential role in activating angiotensin. The activated kallikrein enzyme is destroyed by a kallikrein inhibitor also present in the body fluids.

Why is the myogenic mechanism important?

The myogenic mechanism appears to be important in preventing excessive stretching of blood vessels when blood pressure is increased.

Where can the myogenic response occur and what stimulus does it require?

The myogenic response is inherent to vascular smooth muscle and can occur in the absence of neural or hormonal influences. Most pronounced in arterioles but can also be observed in arteries, venules, veins, and even lymphatic vessels. Myogenic contraction is initiated by stretch-induced vascular depolarization, which then rapidly increases calcium ion entry from the extracellular fluid into the cells, causing them to contract. Changes in vascular pressure may also open or close other ion channels that influence vascular contraction.

How do the endothelial cells affect blood flow?

They can synthesize several substances that can affect the degree of relaxation or contraction of the arterial wall. Some of these are NO and endothelin.

What special mechanism for local blood flow occurs in the kidneys?

Tubuloglomerular feedback, in which the composition of the fluid in the early distal tubule is detected by an epithelial structure of the distal tubule itself called the macula densa. This structure is located where the distal tubule lies adjacent to the afferent and efferent arterioles at the nephron juxtaglomerular apparatus. When too much fluid filters from the blood through the glomerulus into the tubular system, feedback signals from the macula densa cause constriction of the afferent arterioles, in this way reducing both renal blood flow and glomerular filtration rate back to nearly normal.

What are the two main theories for how tissue blood flow is altered?

Vasodilator theory and oxygen demand theory (both are considered metabolic mechanisms)