WEEK 4: Pathophysiology of hypertension Flashcards
Define the following terms.
-Blood pressure
-Systolic BP
-Diastolic BP
*Blood pressure: the force exerted by the blood against the walls of the blood vessels.
-should be adequate to maintain tissue perfusion during activity and rest.
*Systolic BP is a peak pressure reached during systole.
*Diastolic BP is the lowest pressure reached during diastole.
Presently, of all deaths caused by cardiovascular disease, how many % now occur in low-to-middle income countries (LMIC)?
Why does most death occur in LMIC?
Presently, of all deaths caused by cardiovascular disease, 80% now occur in low-to-middle income countries (LMIC).
Due to: low levels of awareness, low treatment and control rates in LMIC
Higher BPs in groups of African ancestry as compared to alternative ethnic groups are noted from a very young age.
In the previous century, cardiovascular disease was mainly a disease of the developed world
-Causes 10,8M deaths/yr
The age at which those from sub-Saharan Africa present with their first myocardial infarction or cardiovascular event (stroke or heart failure) is about how long earlier than from any other global region?
Hypertension may play a particularly important role in the development of what diseases?
The age at which those from sub-Saharan Africa present with their first myocardial infarction or cardiovascular event (stroke or heart failure) is about two decades earlier than from any other global region.
Hypertension may play a particularly important role in the development of heart failure, stroke and myocardial infarction.
People of African ancestry often have a reduced BP response to several antihypertensive drug classes.
Define Mean arterial Pressure.
State the 2 determinants of MAP.
State the formula for MAP.
Definition:
Mean Arterial Pressure (MAP) reflects the average pressure in your arteries during one cardiac cycle.
Mean arterial pressure is determined by cardiac output and total peripheral resistance (also known as systemic vascular resistance- SVR).
MAP = CO X TPR
*CO can be considered circulating volume.
*TPR is the resistance of all vessels in the systemic circulation
Calculate Mean Arterial Pressure for the following.
If a patient’s blood pressure is 120/80 mm Hg.
Formula for MAP:
To calculate MAP, follow this equation:
MAP = 1/3 (Systolic Blood Pressure) + 2/3 (Diastolic Blood Pressure).
For example, if a patient’s blood pressure is 120/80 mm Hg:
MAP = 1/3 (120) + 2/3 (80) = 93.3 mm Hg.
Blood pressure is controlled by a complex combination of processes that influence cardiac output (CO) and total peripheral vascular resistance (TPR or SVR).
Outline the 3 short term control of BP.
Short term mechanisms
*Baroreceptor reflex
*Chemoreceptors
*CNS response to ischemia
Outline the 2 long term control mechanisms of BP.
*Renin- angiotensin- aldosterone system (RAAS)
*Vascular endothelial function
Discuss the baroreceptor reflex effect in the control of BP.
Most cardiovascular disorders, eg hypertension, involve abnormalities of long-term regulation.
Baroreceptor reflex
Main baroreceptors are in carotid sinus, also aortic arch.
*Monitor stretch of vessel wall as index of arterial BP
*Monitor both increases and decreases in BP.
Receptors:
*Aortic arch transmits impulses via vagus nerve to medulla (responds only to ↑ BP).
*Carotid sinus transmits via glossopharyngeal nerve (CN IX) to solitary nucleus of medulla (responds to both ↓and ↑in BP).
In hypertension, the baroreceptors are reset to defend a higher level of BP.
Describe the baroreceptor reflex effect in hypotension.
Hypotension →↓arterial pressure →↓ stretch →
↓afferent baroreceptor firing → (medulla) ↑ efferent sympathetic firing and ↓ efferent parasympathetic stimulation →vasoconstriction, ↑HR, ↑heart contractility, ↑BP.
Chemoreceptors effect in the control of BP.
State the 2 types of chemoreceptors.
Where are they located?
What do they each monitor.
PERIPHERAL CHEMORECEPTORS: located within carotid and aortic bodies. Respond primarily to hypoxemia and hypercapnia (↓PO2 < 60 mmHg), ↑PCO2,and ↓ pH), to elicit hyperventilation, tachycardia, and increased sympathetic vasoconstrictor activity.
CENTRAL CHEMORECEPTORS: Respond to changes in blood [CO2 /H+]. They do not directly respond to PO2. Located in the medulla, brainstem, cerebellum, midbrain and hypothalamus.
Describe the Central nervous system response in control of BP.
Responds within seconds to ischemia of the vasomotor center in the medulla.
*Hypothalamus activates the sympathetic nervous system causing peripheral vasoconstriction and an ↑ in cardiac output.
Discuss the RAAS system response in controlling BP.
Control Na+ excretion & extracellular fluid volume
Renin-angiotensin-aldosterone-system
- Renin (from liver) converts angiotensinogen to angiotensin I
- Angiotensin-converting enzyme (ACE, -from lungs) converts angiotensin I into angiotensin II
Angiotensin II effects
Immediate:
*Vasoconstrictor – increased systemic vascular resistance.
Prolonged:
*Stimulates the adrenal cortex to secrete aldosterone – Na+ and Water retention. This increases blood vol, CO and BP.
Discuss Vascular Endothelium response on controlling BP.
Produce vasoactive substances:
*Endothelium-derived relaxing factor (EDRF) which:
-Helps maintain low arterial tone at rest
-Inhibits growth of the smooth muscle layer
-Inhibits platelet aggregation
*Prostacyclin – (vasodilator and anti-thrombin)
*Endothelial dysfunction may contribute to atherosclerosis & primary hypertension.
Define the following:
-Hypertension
-Isolated systolic hypertension
-Isolated diastolic hypertension
A BP of 140/90 mmHg or higher (dias-syst HTN)
*Isolated systolic hypertension (ISH): SBP> 140, DBP< 90mmHg
*Isolated diastolic hypertension (IDH): DBP> 90mmHg, SBP normal range
What is the American cut-off of BP?
What are Global cut offs non-discriminatory in?
-NB: American cut off is 130/80
-Global cut offs are non-discriminatory in age, ethnicity, sex
State the Diastolic and Systolic ranges for Normal, Prehypertension, Stage 1 hypertension and Stage 2 hypertension.
NORMAL
S: <120
D: <80
PRE-HYPERTENSION
S: 120-139
D: 80-89
STAGE 1 HYPERTENSION
S: 140-159
D:90-99
STAGE 2 HYPERTENSION
S: >160
D: >100
Hypertension can be divided into Primary (essential) hypertension and Secondary hypertension.
State the % incidence for Primary (essential) hypertension.
What is it mostly related to?
Outline the risk factors for Primary hypertension.
Divided into:
Primary (essential) hypertension – occurs in 90-95% cases of hypertension.
*Related to ↑CO or ↑ TPR, or both
Risk factors are ↑age, obesity, diabetes, smoking, genetics/ race, diet, lifestyle.
State the incidence % for Secondary HTN.
What is it mostly related to?
Secondary HTN- occurs in 5% of people.
-Mostly 2° to renal disease (but current research suggests otherwise especially in Black people)
Outline the Complications of HTN.
-Atherosclerosis,
-Left ventricular hypertrophy
-Stroke
-Congestive heart failure
-Renal failure
-Retinopathy
-Aortic dissection.
Discuss the pathogenesis of hypertension.
The pathogenesis of hypertension is Multifactorial- caused by a number of neurohormonal, renal, and vascular mechanisms.
Possible pathogenesis include:
-Genetic predisposition, excess salt intake and adrenergic (sympathetic) tone
-These factors interact to produce hypertension
-Alterations in the structure and function of small and large arteries play a pivotal role in the pathogenesis and progression of hypertension.
Neural Mechanisms OF HTN.
Outline some of the factors that drive Increased sympathetic/ adrenergic tone.
Increased adrenergic tone is associated with increased heart rate and cardiac output.
Increased sympathetic/ adrenergic tone is driven by:
-Deactivation of inhibitory neural inputs (e.g., baroreceptors)
-Activation of excitatory neural inputs (e.g., carotid body chemoreceptors, renal afferents)
-Increased circulating angiotensin II
-Obesity, stress
Outline factors which can alter vascular structure and diameter.
-Vasodilating systems
-Vasoconstriction systems
-Vascular growth factor
VASODILATING SYSTEMS
*Parasympathetic nervous system
*Kallikrein-kinin-system
*Prostaglandins
*EDRF
*Atrial natriuretic factor
VASOCONSTRICTING SYSTEMS
*SNS
*Endothelin
*Calcium
*RAAS
*Quabain
*ADH
VASCULAR GROWTH FACTOR
-Insulin like growth hormone
-Growth hormone
-Parathyroid hormone
-Tissue oncogenes.
Discuss Hormonal Mechanisms of HTN.
E.g. Altered Renin-Angiotensin-Aldosterone-System (RAAS)
-Cause endothelial cell dysfunction, vascular remodeling, and hypertension
-Also cause vasoconstriction
Insulin Resistance & Hyperinsulinemia
-Causes increased re-absorption of sodium by the kidneys
-Insulin can also stimulate the sympathetic nervous system and increased peripheral vascular resistance
Discuss secondary hypertension.
Who may be suspected of secondary hypertension.
Has specific cause which can be identified.
It may be suspected in hypertensives who are:
*Younger than 35 years of age
*Abrupt onset of hypertension
*No Family History
*Failed Empiric therapy
- Life Style modification
- Drug Therapy (usually more than 2-3 drugs)
Outline Identifiable causes of Hypertension.
Renovascular disease
Renal parenchymal disease
Polycystic kidneys
Aortic coarctation
Sleep apnea
Pregnancy
Pheochromocytoma
Primary aldosteronism
Cushing syndrome
Hyperparathyroidism
Hypo/hyperthyroidism
Certain drugs
Define Accelerated HTN.
Defined as a recent significant increase over the baseline BP and is associated with target organ (retinal) damage.
Usually seen as retinal vascular damage on fundoscopy, but without papilledema.
What is papilledema?
What does presence of papilledema would indicate in hypertension?
NB: Presence of papilledema would indicate malignant HTN.
Papilledema refers to swelling of both optic discs in the eyes due to increased intracranial pressure.
What can be used as better prognostic predictors of organ damage and cardiovascular disease risk in various stages of hypertension, including in drug-resistant hypertensive patients?
Home BP
24 h ambulatory BP
