Pathophysiology of Hypertension

Question 1

PULMONARY HYPERTENSION

Answer 1

• Increased blood pressure in the arteries of the lungs
• Can be due to hypoxia, endothelial dysfunction, genetics, blockage/damage to blood vessels, side effects of drugs, left-sided HF
• Right side of the heart has to work harder
• Rare
• More common in patients with another heart or lung condition
• Usually only diagnosed when severe and symptomatic

Question 2

SYSTEMIC ARTERIAL HYPERTENSION

Answer 2

• Systemic arterial hypertension is the condition of persistent non-physiologic elevation of system blood pressure
• Typically defined as:
• Systolic > 140 mmHg and/or
• Diastolic > 90mmHg
• Identified as one of the major causal risk factors for cardiovascular disease

Question 3

RISK FACTORS

Answer 3

• Age
• Weight
• Sex
• < 60 years more prevalent in males
• > 60 years more prevalent in females • Race
• African Americans disproportionally affected
• Education status
• Diet

Question 4

Stage 1 hypertension

Answer 4

• Clinic BP is 140/90 mmHg or higher and subsequent ambulatory or home blood pressure monitoring (ABPM or HBPM) daytime average is 135/85 mmHg or higher

Question 5

Stage 2 Hypertension

Answer 5

Clinic BP is 160/100 mmHg or higher and subsequent ABPM or

HBPM daytime average is 150/95 mmHg or higher

Question 6

Severe Hypertension

Answer 6

• Clinic systolic BP is 180 mmHg or higher

* OR clinic diastolic BP is 110 mmHg or higher

Question 7

PRIMARY HYPERTENSION

Answer 7

Also known as “essential” or “idiopathic” hypertension
• Accounts for ~90 % of human hypertension
• No apparent underlying cause • Weight
• Lifestyle
• Dietary sodium intake, lack of exercise, alcohol, smoking
• Genetic factors
• Multiple organ systems

Question 8

three examples of catecholamines

Answer 8

adrenaline
noradrenaline
isoprenaline (synthetic beta agonist)

Question 9

SYMPATHETIC CONTRIBUTION TO HYPERTENSION

Answer 9

Increased blood pressure due to:
• Increased signalling to vascular smooth muscle cells of blood vessels (a1)

increased vasoconstriction, increased TPR
• Increased signalling to pacemaker
and contractile cells in heart (b1)

increased HR and contraction, increased CO

• Adrenal gland secretion of adrenaline
• Renin secretion (b1 receptors)

Ang II increased and increased vasoconstriction and increased
TPR

increased Na+ and H2O absorption and increased ECV

Question 10

Angiotensinogen:

Answer 10

• a2 globulin
• synthesized by the liver
• released into circulation

Question 11

Renin:

Answer 11

• proteolytic enzyme
• released by granular cells in the juxtaglomerular apparatus (JGA) of the kidney
• cleaves Angiotensinogen to Angiotensin I
• Renin is cleared rapidly from the plasma

Question 12

Angiotensin I:

Answer 12

• appears to have no biological activity

* is a precursor to Angiotensin II

Question 13

• Angiotensin converting enzyme (ACE):

Answer 13

• enzyme
• found in vascular endothelium in the
lungs and the renal afferent and efferent
arterioles
• converts Angiotensin I to Angiotensin II

Question 14

angiostenin 2 effect on vascular smooth muscle

Answer 14

increased vasoconstriction and increased TPR

Question 15

ANGIOTENSIN II effect on the hypothalamus

Answer 15

increased relaeased of vasopressin (ADH)
increased reabsorption fo H20 in the kidneys

increased ECV

Question 16

angiotensin II effect on the renal tubules of the kidney

Answer 16

increased stimulation for the secretion of aldosterone from the adrenal glands
increased sodium reabsorption in the kidney
increased ECV

Question 17

LOW RENIN HYPERTENSION

Answer 17

• Subset of patients with primary hypertension
• It becomes secondary if the cause is known e.g. Conn’s syndrome
• More prevalent in patient who are:
• Older
• Of Afro-Caribbean descent
• Diagnosed using plasma aldosterone:renin ratio
• Low renin, normal aldosterone
• Different treatment strategy

Question 18

ENDOTHELIN

Answer 18

• Most potent endogenous vasoconstrictor
• Endothelin-1 (ET-1) predominant isoform in cardiovascular system
• Circulating concentrations of ET-1 are NOT commonly increased in primary hypertension
• BUT local levels may be increased

Question 19

ENDOTHELIAN bound to ETA receptors

Answer 19

Can bind ETA receptors on vascular smooth muscle cells • VASOCONSTRICTION
• Can bind ETA receptors in cardiomyocytes and increase contactility

Question 20

endothelian bound to ETB receptors

Answer 20

Production of nitric oxide causing VASODILATION

• In the kidneys promotes Na+ and H2O excretion (natriuresis and diuresis, respectively)

Question 21

NITRIC OXIDE

Answer 21

• Lipophilic gas released from endothelial cells in response to stimuli
• Most potent endogenous VASODILATOR
• Very short half-life
• Usually acts in the tissues where it is secreted
• Chronic regulator of RENAL blood flow and increases Na+ excretion

Question 22

REACTIVE OXYGEN SPECIES

Answer 22

Including superoxide, hydrogen peroxide (H2O2) and peroxynitrite
• Patients with essential hypertension have increased circulating H2O2
• ROS in the vasculature may uncouple the enzymes which produce NO
• BUT chronic treatment with antioxidants does NOT lower pressure

Question 23

Zona glomerulosa (aldo)

Answer 23

Conn’s syndrome

Question 24

Zona fasiculata (cort)

Answer 24

Cushing’s syndrome

Question 25

Adrenal medulla (E/NE)

Answer 25

Pheochromocytoma

Question 26

LIFESTYLE MODIFICATIONS

Answer 26

• Weight loss
• Reduced salt (Na+) intake <6g/day
• Increased fruit and vegetable intake (increased K+)
• Reduced alcohol consumption
• Increased aerobic exercise
• Smoking cessation
• Stress reduction / relaxation techniques