7 - Pathophysiology of Hypertension Flashcards
Define hypertension
A condition of chronically elevated blood pressure
How do you diagnose hypertension?
Hypertension can be only be diagnosed based on 2 or more recordings taken in the seated position at 2 or more office visits
What is the range of blood pressure to diagnose hypertension
Systolic = >140 mmHg Diastolic = >90 mmHg
Describe white coat hypertension
“White coat hypertension” is a relatively recently defined phenomenon of high blood pressure only in the clinical setting; despite the episodic nature of this elevation in blood pressure, these patients are also at a higher risk for some of the cardiovascular-related events seen in overtly hypertensive patients
What is one of the main concerns in the treatment of hypertension?
The number of patients not achieving blood pressure control despite being treated
What comorbidities are often seen in patients with hypertension?
- Ischemic heart disease
- Heart failure
- Atrial fibrillation
- Stroke
The pathogenesis of these conditions overlaps with hypertension and can create a vicious cycle, as hypertension increases the risk of these conditions and these conditions increase the risk of hypertension
Describe the relationship between increased blood pressure and the risk for MI, stroke and HF
The risk for MI, stroke, and HF doubles with a 20 mmHg increase in systolic or 10 mmHg increase in diastolic pressure
What is an uncontrollable risk factor for hypertension?
Aging
There is a 90% lifetime risk of developing hypertension in normotensive middle-aged individuals
Describe the general trend of systolic and diastolic pressure before and after the age of 50
Systolic and diastolic blood pressure increase together until about age 50, then diastolic pressure decreases while systolic pressure continues the upward trend
This means that older individuals are more likely to have isolated systolic hypertension than systolic and diastolic hypertension and younger individuals are more likely to have isolated diastolic hypertension
How does aging contribute to hypertension?
The aging process impairs cardiac function, reducing diastolic pressure, and alters vascular function, increasing systolic pressure
What is a controllable risk factor for hypertension?
Obesity
As BMI increases, the prevalence of hypertension also increases
What factors underlie the pathogenesis of obesity-related hypertension?
Many factors have been proposed to underlie the pathogenesis of obesity-related hypertension…
- enhanced sympathetic activity/ responsiveness
- activation of the renin-angiotensin-aldosterone system (RAAS)
- metabolic disturbances
These factors ultimately change vascular and renal function to increase blood pressure
Describe the organ damage that hypertension can lead to
Hypertension initiates damage to organs, including vasculopathy, cerebrovascular damage, heart disease, and nephropathy
In addition, secondary processes are activated to exacerbate damage
Describe cardiac remodeling which can result from chronically elevated blood pressure
- Ventricular hypertrophy occurs as the heart responds to the high afterload
- Hypertrophy increases the risk of cardiovascular incidents including MI, HF and sudden cardiac death from a fatal arrhythmia or embolism
- Treating hypertension can decrease risks
Where else can remodeling occur due to hypertension?
In he vasculature
What is atherosclerosis?
Vascular remodeling and plaque formation
What two factors can induce remodeling in the vasculature?
- Sheer stress on the vessels
- Hormonal factors such as Angiotensin II
How does Angiotensin II mediate vascular remodeling?
Angiotensin II mediates vascular remodeling through activation of intracellular signaling cascades to alter vascular tone directly and gene expression
What is another process involved in the pathogenesis of hypertension?
Inflammation
How is inflammation activated by hypertension?
Hypertension can activate a T cell-mediated response and further exacerbate end-organ damage
How does inflammation contribute to organ damage?
Inflammation alters the oxidative capacity in the immune cells and reactive oxygen stress can influence vascular tone and protein expression
What does RAAS contribute to hypertension?
The renin-angiotensin-aldosterone system (RAAS) also contributes to immune activation in hypertension.
What are the two components of regulating short-term blood pressure?
1 - neural reflex arcs
2 - total peripheral resistance
What is the purpose of neural reflex arcs?
To modulate heart rate
What are the two major neural reflex arcs?
- baroreflexes
- chemoreflexes
Where do baroreceptors exist? What do they detect?
- Carotid sinus
- Atria
- Pulmonary arteries
Baroreceptors detect blood pressure throughout the vascular tree
Where do baroreceptors send their signals regarding current blood pressure?
Into the CNS (medulla of brain)
What is the purpose of sending this information to the CNS?
Modulation of sympathetic and parasympathetic outflow
What can sympathetics and parasympathetics do with the information they receive regarding blood pressure?
Project to areas of the periphery including the heart and vasculature in order to modulate heart rate and total peripheral resistance
What are the key steps and components of a reflex arc?
- Stimulus to be detected by a sensory receptor (“detector”)
- Sensory info is transmitted to an integration center
- Integration center compares afferent information from several sites to determine the appropriate effector response
- Effector response serves to modulate the initial stimulus, changing the activity of the sensory receptor (“detector”)
How does the reflex arc and feedback loop work for the arterial baroreflex?
Activation of the reflex results in a reduction of the sensed stimulus, meaning that an increase in BP will cause a decrease in BP and vise versa
What type of receptors are baroreceptors? What are they activated by?
baroreceptors are mechanosensitive sensory receptors, activated by the distending pressure in the carotid or atria (stretch receptors)
Increased stretch of the wall generates an action potential in the nerve ending
Why are baroreceptors not involved in long-term maintenance of BP?
Because they sense both actual stretch and how the stretch is changing with time
If the stretch is not changing with time (a period of extended stretch), the baroreceptors will “reset” to the new “normal”
What is the main integration center in the brain for sensory information from baroreceptors?
Nucleus of the solitary tract (NST) in the medulla of the brainstem
What happens to the sensory information at the NST? Where does the information go from there?
- The sensory information is integrated with information from the hypothalamus before it is projected to other brain regions
- These other brain regions are important for modulation of total peripheral resistance, stroke volume, heart rate, parasympathetic tone, vagal tone and sympathetic tone
- The projections then flow into the periphery and synapse in the sympathetic chain and parasympathetic ganglia
Where are chemoreceptors located?
The effector sensors of the chemoreflex are located in similar locations as the arterial baroreceptors, in the glomus cells of the carotid body and aortic bodies
What is the integration site for chemoreceptors?
Same as baroreceptors
NTS - Nucleus of the Solitary Tract
What happens when chemoreceptors detect low O2, high CO2 or low pH?
Vasoconstriction and bradycardia
What accompanies this response?
This intrinsic response is mitigated by changes in ventilation that accompanies this response, as well as the activation of other chemoreceptors, to increase ventilation, which will cause a tachycardia.
What is one source of long-term regulation of blood pressure?
Hormones
What is a potent vasoactive substance that alters blood pressure?
Angiotensin II
What is the role of angiotensin II?
Angiontensin II causes….
- Direct vasoconstriction
- Moderate sodium reabsorption
- Stimulates aldosterone secretion from the adrenal gland, which promotes even greater sodium reabsorption from the kidney
How is angiotensin II produced?
By angiotensinogen released from the liver
It then gets to the kidney where renin cleaves it into angiotensin I
Once angiotensin I gets to the pulmonary vasculature angiotensin-converting enzyme (ACE) cleaves it into the vasoactive form of angiotensin II
What three processes is angiotensin II involved in (think rapid, slow and long-term)?
- Rapid vascular response
- Slow renal response
- Long-term remodeling
What is an organ that plays a predominant role in long-term blood pressure regulation?
Kidney
How does the kidney accomplish this?
Through regulating changes in sodium and water excretion
think blood volume
What happens when there is low arterial pressure in regards to the kidney?
Renal mechanisms to conserve water and salt are activated
What happens when there is high arterial pressure in regards to the kidney?
Renal mechanisms to increase the excretion of salt and water are activated
In what other way can changes in pressure alter kidney function?
Changes in pressure alter the filtration capacity of the glomeruli in the kidneys to alter the amount of water filtered
What is the effect of high pressure on the filtration capacity in the kidney
High pressure will increase resistance and therefore result in increased sodium excretion (water will follow) leading to a decreased blood volume
What is this relationship of filtration regulation referred to as?
Pressure-natriuresis
What can we infer about the effects of kidney damage on blood pressure
Any dysfunction of renal sodium and/or water handling will result in abnormal blood pressures
What will happen with a reduction in kidney mass or an enhanced tubular reabsorption of sodium?
Decreased glomerular capillary filtration and an inappropriate retention of sodium and water leading to hypertension
What is secondary hypertension?
Hypertension is classified based on the underlying pathology, so secondary hypertension is any hypertension resulting from a known cause
The known cause (primary) issue results in (secondary) hypertension
What is primary hypertension? What else do we call this?
Hypertension in which no one causal factor can be identified
AKA essential hypertension
What is renovascular disease?
Renovascular disease can result due to plaque formation in the renal artery, other stenotic processes, or vascular dysfunction
Pretty much, the RENAL ARTERY is impaired
How do renal baroreceptors react to renovascular disease?
They detect a drop in blood pressure and respond by releasing renin in an attempt to increase circulating angiotensin II
What does increasing angiotensin II do?
Increases vascular resistance and inhibits natiuresis and diuresis at the level of the nephron (retains water)
What is obstuctive sleep apnea and how does it cause secondary hypertension?
OSA is a type of sleep apnea which results in intermittent hypoxic episodes which induce chemoreceptors to signal low oxygen
What do the chemoreceptors do during hypoxic states?
Send a sympathoexcitatory reflex which increases sympathetic nerve activity to change ventilation, increase renin secretion
The goal is to increase ventilation and heart rate to decrease CO2 and increase O2
What factors may contribute to OSA-related hypertension?
- Vascular dysfunction
- Obesity
- Chronic stress (lack of sleep)
- Inflammatory processes
How do you treat secondary hypertension?
Treat the primary insult
Do NOT treat the hypertension
How do you treat a patient with renovascular hypertension?
Correct the vascular lesion via surgery
How do you treat a hypertensive patient with renal parenchymal disease?
Replace the kidney
How do you treat a hypertensive patient with coarctation of the aorta?
Fix the aorta
How do you treat a hypertensive patient with Cushing’s disease and pheochromocytoma?
Excise the tumor
How do you treat a hypertensive patient with OSA or obstructive sleep apnea?
Open the airway
- This is a good strategy theoretically but not clinically effective
- This may be due to changes that occur centrally and/or the presence of co-morbidities
Do the majority of hypertension patients have primary (essential) or secondary hypertension?
Primary (essential) hypertension where no one factor can be identified
What are the general causes of primary (essential) hypertension?
Genetic
- renal abnormalities
- RAAS mutations
- immunity
- salt-sensitivity
- sympathetic hyperactivity
Environmental
- stress
- high salt intake
- drug abuse
- alcohol abuse
What three organ systems have been shown to be dysfunctional in hypertension
Each play a role
- CNS dysfunction
- Vascular dysfunction
- Renal dysfunction
What is the benefit of lowering blood pressure?
Lowering blood pressure is associated with improved outcomes and reduced burden of comorbid factors
What is the first line in treating essential hypertension?
Lifestyle modification
What are the lifestyle modifications which can be effective?
- Weight reduction ***
- DASH eating plan ***
- Dietary sodium restriction
- Physical activity
- Moderate or low alcohol consumption
*** two most effective methods
When lifestyle modification is ineffective, a medication plan is indicated. What is the typical drug therapy?
- Diuretic is indicated first
- Then a combination of a RAAS target, calcium channel blocker or a beta blocker
The combination of drugs used depends on the level of blood pressure
Why do patients on blood pressure medications need to be closely monitored?
An “escape” mechanism can develop and high blood pressure can recur, even on medication
What do medications targeting RAAS accomplish?
Therapeutics aimed at RAAS targets not only reduce resistance and sodium/water retention but also reduce cellular remodeling and are thought to reduce inflammatory processes
What is a growing concern in the pharmacological treatment of hypertension?
Resistant or refractory hypertension
This means that the blood pressure goal is not reached with 3 or more pharmacological agents
What treatments are indicated in the case of resistant or refractory hypertension?
- Carotid sinus stimulator
- Renal denervation therapy
What is a carotid sinus stimulator?
- A carotid sinus stimulator is implanted around the carotid sinus and programmed to activate the baroreflex
- This reduces blood pressure on the long-term (years) in patients and seems to be well-tolerated
What is renal devervation therapy?
- A more controversial therapy
- A device ablates the renal nerves and lowers BP by reducing sympathetic outflow from the CNS
- While it has been proven to be safe, the BP lowering effect has been mixed
