Flashcards in Physiology of HTN Deck (47)
- consistently high BP of at least 140/90
What is primary HTN?
- idiopathic, no recognizable cause (just haven't figured it out yet - genetic?)
Causes of Secondary HTN?
- kidney problems
- adrenal gland tumors - pheochromocytoma
- thyroid problems
- certain defects in blood vessels you're born with - aortic coarction
- certain meds, such as OCPs, cold remedies, decongestants, OTC pain relievers, and some Rx drugs
- illegal drugs: cocaine (severe coronary artery vasoconstriction) and amphetamines
- alcohol abuse or chronic alcohol use
What are the physiological mechanisms involved in development of primary HTN?
- peripheral resistance
- other factors:
ANP, bradykinin, endothelian, and EDRF (endothelial derived relaxing factor) or nitric oxide
Main factors in HTN?
- Increased CO (increased preload and increased contractability)
- increased peripheral resistance (functional constriction amd structural hypertrophy)
increased COxincreased peripheral resistance = HTN
What is systolic BP?
- force that blood exerts on artery walls as the heart contracts to pump out the blood
- high systolic pressure known to be greater risk factor than diastolic for heart, kidney, and circulatory complications and for death, particulary in middle aged and elderly adults. Wider the spread b/t systolic and diastolic, the greater the danger
- measurement of force as heart relaxes to allow blood to flow into heart, high diastolic is strong indicator of heart attack and stroke in young adults
What is the mean arterial pressure?
- as blood is pumped out of LV into arteries, pressure is generated. The mean arterial pressure (MAP) is determined by the CO, systemic vascular resistance and central venous pressure according to the following relastionshop which is based upon relationship between flow, pressure and resistance
MAP = (COxSVR) - CVP
What is the arterial pulse pressure?
- difference b/t systolic and diastolic readings during ejection
- it appears to be an indicator of stiffness and inflammation in the blood vessel walls
- the greater the difference the stiffer and more injured the vessels are thought to be
- may be a strong predictor of heart problems, particularly in older adults
What is peripheral vascular resistance?
- resistance to flow that must be overcome to push blood through the circulatory system
- resistance offered by the peripheral circulation is called the systemic vascular resistance
What are the neural mechanisms that affect BP?
ANS: intrinsic circulatory reflexes, and higher neural control
Intrinsic: baroceptors and chemoreceptors
extrinsic: pain, cold, isometric exercises
CNS: change in mood or emotion
Neural control of BP?
- sympathetic and parasympathetic divisions of ANS
- contributes through control of CV function through modulation of cardiac and vascular function
- located in medulla oblongata
- three distinct pools that lead to sympathetic innervation of the heart and blood vessels
- vasomotor center and cardioinhibitory center (primarily paraympathetic: vagus nerve)
What are arterial baroceptors and where are they located?
- most impt arterial baroreceptors are located on carotid sinus (at bifurcation of external and internal carotids) and in aortic arch
- respond to stretching of the arterial wall
- as arterial pressure suddenly rises, the walls of these vessels passively expand, which stimulated the firing of these receptors
- inhibits central sympathetic d/c
- the carotid sinus is most impt for regulating arterial pressure
- aortic arch receptors have higher threshold pressure and are less sensitive than the carotid sinus receptors
What are the arterial baroceptors responsible for?What happens when there is a chronic change in BP?
- postural baroreflex: rapid moment to moment adjustmens in BP: change in position
- with chronic changes, the baroreceptors tend to reset to adjust to the increasing CO or arterial pressure and are not as good at regulating the mechanisms to cause a decrease in sympathetic activity
What are the chemoreceptors?
- sensitive to O2, CO2, H+ concentration in the blood
- located in carotid bodies which lie in the bifurcation of the 2 common carotids and aortic bodies of the aorta
- communicate with vasomotor center and can induce widespread vasoconstriction
What controls autonomic regulation of cardiac function?
- parasympathetic: vagus nerve
- sympathetic: SA and AV nodes
Stimulation of autonomic regulation?
- sympathetic stimulation can cause both arteriolar constriction and arteriolar dilation, the ANS has impt role in maintaining a normal blood pressure
- parasympathetic nervous system contributes to the regulation of the heart function, but has little control over the blood vessels
Autonomic neurotransmitters involved in BP control?
- Acetylcholine is postganglionic neurotransmitter for parasympathetic neurons (cholinergic receptors)
- NE is main neurotransmitter for postganglionic sympathetic neurons (adrenergic receptors)
- 2 types of adrenergic receptors: alpha and beta
in vascular smooth muscle, stimulation of alpha receptors produces vasoconstriction and stimulation of b receptors causes vasodilation
Epi and NE effect on BP?
- little evidence to suggest that epi and NE have role in HTN, impt because drugs that block SNS do lower BP and have well established therapeutic role
- Catecholamines (E and NE) act on heart and blood vessels through alpha and beta receptors so the CV actions of catecholamines can be blocekd by tx with alpha and beta blockers
CNS responses to change in BP?
- CNS ischemic response
- cushings reflex
Autonomic response to circulatory stresses?
- postural stress
- valsalva's maneuver
- face immersion - (used to break Vtach)
CO and PVR effect on BP?
- BP = COxPVR
- most people with essential HTN have normal CO but raised PVR
What determines the PVR?
- not by large arteries or capillaries but by small arterioles, walls of which contain smooth muscle cells
- contraction of smooth muscle cells is thought to be related to rise in intracellular Ca2+ concentration
- prolonged smooth muscle contraction is thought to induce structural changes with thickening of arteriolar vessel walls possible mediated by angiotensin, leading to an irreversible rise in PVR.
- this may explain the vasodilatory effect of drugs that block the Ca channels (CCBs)
Role of the RAAS?
impt role in regulating blood volume and systemic vascular resistance, which together influence cardiac output and arterial pressure
What are the 3 impt components in RAAS?
MOA of RAAS?
- renin gets released from the kidneys because of low BP- stimulates the formation of angiotensin 2 from angiotensin 1 which then in turn stimulates the release of aldosterone from the adrenal cortex
Where is renin released from? When is it released?
- renin is secreted from juxtaglomerular apparatus of the kidney located in the wall of the afferent arteriole
- released in response to glomerular underperfusion or reduced salt intake
- also released in response to stimulation from the sympathetic nervous system
MOA of renin release?
- JG cells assoc with afferent arteriole entering glomerulus are the primary site of renin storage and release in the body
- a reduction in afferent arteriole pressure causes the release of renin from JG cells, whereas incerased pressure inhibits renin release
- B 1 adrenoceptors located on JG cells respond to sympathetic nerve stimulation by releasig renin
- specialized cells (macula densa) of distal tubules lie adjacent to the JG cells of the afferent arteriole (the macula densa senses the amt of sodium and chloride ions in the tubular fluid
- when NaCl is elevated in the tubular fluid, renin release is inhibited, if NaCl reduced - stimulates renin release by the JG cells
- evidence that prostaglandins stimulate renin release in response to reduced NaCl transport across the macula densa
- when afferent arteriole pressure is reduced glomerular decreases and this reduces NaCl in the distal tubule
- this serves as an impt mechanism contributing to the release of renin when there is afferent arteriole hypotension
Renin effect on angiotensinogen?
- when renin is released into the blood, it acts upon a circulating substrate, angiotensinogen, that undergoes proteolytic cleavage to form the decapeptide angiootensin I
- vascular endothelium, particularly in the lungs, has an enzyme ACE, that cleaves off 2 AAs to form the octapeptide - angiotensin II, although many other tissues also can form AII (brain, heart, and vascular). AII is a potent vasoconstrictor and thus causes a rise in BP
Impt functions of AII?
- constricts resistance vessels thereby increasing systemic vascular resistance and arterial pressure
- acts on adrenal cortex to release aldosterone, which in turn acts on the kidneys to increase Na+ and fluid retention
- stimulates the release of vasopressin (ADH) from the posterior pituitary, which increases fluid retention by the kidneys
- stimulates thirst centers within the brain - add more volume - increase BP
- facilitates NE release from the nerve endings and inhibits NE re-uptake by nerve endings, thereby enhancing sympathetic adrenergic function
- all going to increase in PVR and increase BP
Function of aldosterone?
major target of aldosterone is the distal tubule of the kidney, where it stimulates exchange of Na+ and K+
- 3 primary physioligic effects of aldosterone result:
increased resorption of Na: Na loss in urine is decreased under aldosterone stimulation
- increased resorption of water, with consequent expansion of ECF volume. This is osmotic effect that is directly related to increased resorption of Na+
- increased renal excretion of K+
What are the 2 most signifcant regulators of aldosterone?
- AII: activation of renin-angiotensin system as a result of decreased renal blood flow results in release of angiotensin II which stimulates aldosterone secretion
- concentration of K ions in ECF: small increases in blood levels of K strongly stimulate aldosterone secretion - K+ will be secreted
What does the RAAS result in?
- either sympathetic sim, hypotension, or decreased Na delivery stimulates kidney to secrete renin this in turn activates angiotensinogen to turn into AI and then AII and this production of AII leads to stimulation of production of aldosterone from adrenal cortex wand ADH secretion from pituitary gland - both of these lead to increased Na and fluid retention in kidneys and lead to increased blood volume
-AII stimulates thirst center in brain also - increases blood volume
- AII leads to cardiac and vascular hypertrophy as well as systemic vasoconstriction
How can the RAAS be therapeutically manipulated?
- very impt in txing HTN and HF
- ACEIs, all receptor blockers and ARBs, are used to decrease arterial pressure, ventricular afterload, blood volume and hence ventricule preload, as well as inhibit and reverse cardiac and vascular hypertrophy
What populations don't respond well to ACEIs?
- many HTN pts have low levels of renin and AII - especially elderly and African Americans. So drugs that block Renin-angiotension system aren't particularly effective for elderly and African Americans
- pop better managed with diuretics, CCBs or B blockers
What are natriuretic peptides
RAAS pathway is regulated not only by mechanisms that stimulate renin release but also modulated by natriuretic peptides (ANP and BNP) released by the heart
- these peptides act as impt counter-regulatory system for RAAS
- involved in long term regulation of Na and water balance, blood volume and arterial pressure
What are the 2 major pathways of natriuretic peptide actions?
1: vasodilator effects: dilate arteries and veins, decrease systemic vascular resistance, and reduce CO
2: renal effects that lead to natriuresis and diuresis: increase GFR, increase Na and fluid excretion, spare K+, and decrease renin release
What is the atrial natriuretic peptide (ANP)?
- hormone from the atria of the heart in response to atrial distension due to increased blood volume, AII stimulation, endothelin and sympathetic stimulation (beta-adrenoreceptor mediated)
- its effect is to increase Na and water excretion from the kidney as a sort of natural diuretic. A defect in this system may cause fluid retention and HTN
- if ANP high - R atrial pressure is high (may see JVD)
What is the BNP?
- brain-type natriuretic peptide
synthesized within ventricles, as well as brain
- released by the same mechanism that releases ANP
- acts similarly to ANP
- if ventricles distended: elevated BNP
What is endothelial dysfunction?
- vascular endothelial cells play a key role in CV regulation by producing a number of potent local vasoactive agents
- nitric oxide (vasodilator) and endothelin (vasoconstrictor)
What is nitric oxide?
- produced by arterial and venous endothelium and diffuses throughout the vessel wall into the smooth muscle causing vasodilation
What is endothelian?
- produces a salt sensitive rise in BP and also activates local renin- angiotensin systems, also effects intracellular calcium (Too much)
What is Bradykinin?
- potent vasodilator that is inactivated by angiontenin converting enzyme
- ACEIs may exert some of their effect by blocking the bradykinin inactivation
- This increase in bradykinin causes the cough associated with ACEI therapy
How does hypercoagulabilty contribute to BP changes?
- HTN pts demonstrate abnormalities of vessel wall (endothelial dysfunction and damage), the blood constituent, abnormal levels of homeostatic factors, platelet activation and fibrinolysis and blood flow suggest that HTN confers a prothrombotic or hypercoagulable state. These components appear to be related to target organ damages
What are the vasodilating systems in the body?
- endothelial derived relaxant factor
- atrial natriuretic factor
- renin-angiotensin systems