Week 11 Flashcards
describe metabolic regulation of brain blood flow. hint: does metabolic regulation occur in the entire brain at once??
The most active brain regions receive increased blood flow and are hyperemic (blood flow exceeds aerobic requirements). Metabolic activity, especially the production of K+, adenosine, and nitric oxide, stimulate vasodilation. Astrocytes also play a role in secreting vasodilator chemicals (prostaglandin E2 and carbon monoxide) when stimulated by glutamate. Astrocytes may also stimulate release off vasodilators like NO.
Neurons, astrocytes, and arterioles all work together and this is termed Neurovascular Coupling and causes functional hyperemia (increased blood flow in response to activity)
Explain how frostbite occurs, why is skin susceptible to temperature damage?
skin maintains constant deep-body temperature through thermoregulation by adjusting blood flow though constriction and dilation of arterioles and Arteriovenous Anastomoses (direct hunts from arterioles to venules). When temperature is low, cutaneous vasoconstriction occurs so that less heat will be lost from the body. Skin appears rosy because blood is diverted to superficial capillary loops, but total cutaneous blood flow and rate of heat loss is lower. In extreme cold, blood flow is so severely restricted that tissue dies, this is frostbite (frozen water also punctures cell membranes and kills them).
What happens to cutaneous blood flow when temperature is warm or person is exercising? How does hot/humid environment or restrictive clothing effect this process? Emotions?
Decreased adrenergic sympathetic effects allow cutaneous arterioles to dilate. With more heat, increased sympathetic cholinergic axons cause vasodilation. They also stimulate sweat glands to lose heat by evaporation and release Bradykinin (vasodilator). Exercise (and fight or flight) cause vasodilation in cutaneous vessels and vasodilation in muscles, lowering peripheral resistance. However, arterial pressure is still high because of increased cardiac output. In hot/humid weather and restrictive clothing, vasodilation can persist after exercise and the blood pressure falls causing loss of consciousness and death. Emotional states can also effect sympathetic activity and cause “cold sweat” or blushing
*What are the most important variables affecting blood pressure. What controls these variables
- cardiac rate
- stroke volume (determined by blood volume)
- total peripheral resistance
Kidneys control blood volume and thus stroke volume while sympathoadrenal system controls total peripheral resistance and cardiac rate
*How is blood pressure sensed and then maintained within normal limits on a beat-to-beat basis? describe the pathway from sense to integration to effector
Baroreceptor Reflex:
Baroreceptors (stretch receptors) located in the Aortic Arch and Carotid Sinuses sense increased/decreased blood pressure and stimulus ascends via the Vagus (X) and Glossopharyngeal (IX) nerves to the medulla oblongata. Here the vasomotor control center regulates the degree of vasoconstriction and vasodilation to regulate peripheral resistance. The cardiac control center regulates cardiac rate. Both of these centers in the medulla act through parasympathetic and sympathetic axons to the heart and blood vessels to cause their effects. Blood pressure is MAINLY regulated by total peripheral resistance and secondly by cardiac output.
describe what happens when a person goes from lying to standing position quickly
Blood pools in the lower extremities and reduces venous return and cardiac output, but the fall in blood pressure is almost immediately compensated for by the baroreceptor reflex. Decreased baroreceptor sensory stimulation along vagus and glossopharyngeal nerves to medulla results in inhibited parasympathetic activity and increased sympathetic activity, increasing cardiac rate and vasoconstriction to maintain blood pressure upon standing.
How can you manually stimulate the baroreceptor reflex to lower blood pressure?
Massaging the carotid sinus stimulates the baroreceptors to lower blood pressure. Slowing of cardiac rate can lead to loss of consciousness or even cardiac arrest. Martial artists also use the carotid sinus as a target to cause unconsciousness.
How did Elvis die
Elvis was on barbiturates which causes constipation and reduced heart rate. His colon was enlarged, as was his heart. He died on the toilet while performing Valsalva’s maneuver (bearing down as if attempting forceful exhalation while preventing air from escaping the mouth/nose) which increases thoracic pressure and stimulation of parasympathetic nervous system (slows heart rate). The combined effect of suppressive drugs, constipation, enlarged heart, and Valsalva’s maneuver lead to decreased heart rate and a cardiac arrhythmia causing death.
How was blood pressure first measured? how is it measured now?
Stephen Hales inserted a cannula into a horse artery and measure the heights which blood would rise (systolic) and fall (diastolic). Now we use Korotkoff’s indirect, auscultatory method. A sphygmomanometer cuff with inflatable bladder is wrapped around upper arm while a stethoscope is applied over the brachial artery. The cuff is inflated and arteries are silenced (closed off). As pressure lowers, a First Korotkoff Sound (tapping) is heard when cuff pressure = systolic pressure and turbulent flow occurs. Pressure keeps dropping until cuff pressure = diastolic pressure and the Last Korotkoff Sound is heard, silence (or just muffled sounds) occurs now because laminar flow is occurring instead of turbulent flow.
What is average blood pressure in the pulmonary arteries, how does this compare to systemic circulation? What causes the pulmonary pressure to be different?
Systemic pressure is 120/80 while pulmonary is 22/8, way lower! However, cardiac output from the right ventricles must be equal to that of the left ventricle. So since cardiac output is the same, it is the lowered peripheral resistance that causes lowered pulmonary pressure. Since the right ventricle has a lower resistance, it has a lighter workload and its walls are thinner
What is felt when you take a pulse? What is pulse pressure? How is mean arterial pressure different?
When you palpate an artery (radial artery) you feel expansion of the artery in response to beating of the heart, so pulse is a measure of cardiac rate. Expansion occurs as a result of a rise in blood pressure after ventricle ejects blood. Because pulse is produced by a rise in pressure from diastolic to systolic levels, the difference between these two pressures is called Pulse Pressure. This is a reflection of stroke volume. Mean arterial pressure represents average arterial pressure during the cardiac cycle
What is hypertension and what causes it? two types
Hypertension = blood pressure in excess of the normal range (130/80 or higher). Secondary hypertension is a result of some other disease like renal failure or adrenal tumor or arteriosclerosis of renal arteries, increasing blood volume and secreting vasoactive chemicals from the kidney. Primary/Essential Hypertension is the result of complex and poorly understood processes. High salt diet induces hypertension (increase osmolality, ADH secretion, increase water reabsorption and blood volume). Kidney’s ability to excrete Na+ declines with age. High aldosterone may also stimulate salt and water reabsorption.
What mechanisms occur during essential hypertension that may act to raise blood pressure? What is the final common pathway in causing hypertension?
Baroreceptor reflex is chronically active to try to lower blood pressure, but sometimes sympathoadrenal activation increases and causes vasoconstriction which raises blood pressure. Artery epithelium also secretes endothelin (which is a vasoconstrictor) and decreases nitric oxide secretion (a vasodilator). There are lots of confusing factors in hypertension, A study in obese rats showed that leptin may increase sympathetic activation and increase blood pressure.
Whatever the cause, the kidneys should be able to compensate by lowering blood volume, so kidney function is the final common pathway in essential hypertension
What are treatments for hypertension and how do they work?
Lowering salt in the diet is recommended as well as increasing potassium, which increases renal flow and acts as a diuretic to lower blood volume. Other important lifestyle modifications are cessation of smoking, moderating alcohol intake, and exercise/weight reduction.
Drug treatments include diuretics to increase urine volume and lower blood volume, B1-adrenergic receptor blockers (atenolol), ACEIs (angiotensin converting enzyme inhibitors), calcium channel blockers, and ARBs (angiotensin II receptor blockers). ACEI and ARBs are most commonly prescribed.
What are the dangers of hypertension
Hypertension is the “silent killer” because most are asymptomatic until substantial damage occurs. Problems from hypertension include a high after load that makes it difficult for ventricles to eject blood. Ventricles thus work harder and this causes pathological growth (hypertrophy) that increases risk of arrhythmias and heart failure. High pressure may also damage cerebral blood vessels leading to a cerebrovascular accident (stroke). Hypertension also contributes to development of atherosclerosis which leads to heart failure and stroke.
Define shock and name the types of shock (briefly define them)
Circulatory shock occurs when there is inadequate blood perfusion of tissues caused by pump failure, bleeding, or vessel dilation.
Hypovolemic shock = due to low blood volume (hemorrhage, dehydration, burns)
Septic shock = due to abnormal immune response to infection
Anaphylactic shock = due to severe allergic reaction, often from bee stings and penicillin which directly enter blood stream, that releases histamine (vasodilator) and decreases peripheral resistance
Neurogenic shock = sympathetic tone is decreased, usually due to upper spinal cord damage or spinal anesthesia (raccoon eyes occur)
Cardiogenic shock = due to cardiac failure, commonly from infarction or severe arrhythmia or valve damage
Explain what causes hypovolemic shock
Hypovolemic shock occurs due to low blood volume from hemorrhage, dehydration, or burns. This decreases blood pressure and cardiac output and activates the baroreceptor reflex to produce tachycardia and vasoconstriction. Decreased blood flow to kidneys causes renin secretion (activates aldosterone) and ADH to conserve water. Capillary filtration also decreases to raise blood volume at the expense of interstitial fluid volume. Result is a person with low blood pressure, rapid pulse, cold clammy skin, and reduced urine output. The blood that remains is diverted to the brain and heart.
*Explain what causes septic shock
Sepsis (life threatening immune response to infection) with persistent hypertension causes septic shock. This occurs due to gram negative bacteria with a cell wall lipopolysaccharide called Endotoxin that activates the enzyme Nitric Oxide Synthase (within macrophages) to produce nitric oxide and promote vasodilation. This causes a dangerous fall in blood pressure. Drugs that inhibit nitric oxide are effective treatments.
(endotoxin also causes Disseminated Intravascular Coagulation!)
What is congestive heart failure and what causes it
CHF is when cardiac output is insufficient to maintain the blood flow required. May be due to heart disease or hypertension. Common disease causes are myocardial infarction, aortic valve stenosis, and incompetence of the aortic/bicuspid valves. This can become a vicious cycle of positive feedback where a myocardial infarction occurs and causes heart failure that causes arrhythmia that cause more infarctions and so on.
CHF can also result from electrolyte imbalances. Excessive plasma K+ and low Ca2+ stop heart in diastole (vice versa stops in systole).
Describe the results of congestive heart failure
Increased venous volume and pressure results. Failure of left ventricle raises left arterial pressure and produces pulmonary congestion and edema, causing shortness of breath and fatigue, can be fatal. Failure of right ventricle raises right arterial pressure and causes congestion and edema in the systemic circulation. Reaction of the body is similar to hypovolemic shock, the sympathetic system increases heart rate/contractility and vasoconstriction while renin increases. Result is elevated blood volume along with chronically low cardiac output and hypertrophy of ventricles
Describe the two categories of immune system
Innate/nonspecific immunity: inherited mechanisms in epithelial membranes including skin and mucous membranes. these are a physical barrier to pathogens and secrete antimicrobial peptides. Some also have strong acidity to kill pathogens and phagocytosis. Genes are inherited and so limited, and innate immunity combats whole categories of pathogens (like gram-negative lipopolysaccharides/endotoxin)
Adaptive/specific/acquired immunity: a function of lymphocytes that improve ability to fight infection after prior exposure (immunological memory). Adaptive immunity also increases innate immunity effectiveness (trained immunity). Specific features of pathogens are recognized by an enormous number of varied genes (not inherited) produced by genetic changes in lymphocytes during life.
Describe activation of innate immunity, what molecules are recognized? What recognizes them? Give two examples of this activation pathway
Pathogen Recognition Receptors (PRRs) recognize Pathogen-Associated Molecular Patterns (PAMPs) that are unique to invaders and produce an immune response. Genes encoding PRRs are inherited.
Toll-like receptors are a PRR stimulated by Lipopolysaccharides (LPS, endotoxin) which are PAMPs in membranes of gram-negative bacteria. The toll-like receptors on dendritic cells and macrophages then secrete chemokine and cytokines to promote immune response (both innate and adaptive!)
NOD-like receptors are a PRR located in the *cytoplasm and recognize intracellular molecules from bacteria. Then they form inflammasomes which activated Caspase to produce cytokines, leading to apoptosis. (Crohn’s disease is a result of mutated NOD genes)
Describe the complement system. What activates it?
The complement system integrates innate and adaptive immune responses. Proteins in the plasma become activated when antibodies bond their molecular targets (antigens) and the antigen-antibody complex then activates complement proteins (innate system) that promote phagocytosis and lysis of the target cell.
