Pathophysiology of Hypertension

Question 1

Distinguish between systemic and pulmonary hypertension.

Answer 1

• Systemic hypertension much more common
• Pulmonary artery pressure is hard to measure.
• Pulmonary hypertension is usually only diagnosed when severe and symptomatic
• Both can be idiopathic or associated with other diseases

Question 2

What are the main causes of pulmonary hypertension ?

Answer 2

• Hypoxia
• Endothelial dysfunction (change in normal function/reactivity of vasculature)
• Genetics (predisposition, e.g. sickle cell anaemia causing blockage)
• Blockage/damage to pulmonary blood vessels (PE; sickle cell etc.)
• Side-effects of some drugs
• L sided heart failure (blood will accumulate in pulmonary circulation and increase P)

Question 3

Define hypertension.

Answer 3

State of persistent elevated arterial BP

Question 4

What are the main kinds of hypertension ? Distinguish between them.

Answer 4

Primary Hypertension

• Idiopathic (difficult to resolve in the long term, no primary cause to target)
• 90% of all cases

Secondary Hypertension

• Known cause (e.g. renal disease, phaeochromocytoma, diabetes through changes in endothelial cell function, Cushing’s, some drugs and toxins)
• 10% of all cases

Question 5

What are phaeochromocytoma and Cushing’s disease related to hypertension ?

Answer 5

Phaeochromocytoma: tumour of chromaffin cells, usually benign, derived from adrenal medullary tissue cells and characterized by the secretion of catecholamines

Cushing’s: Pituitary tumour resulting in increased cortisol

Question 6

How else can hypertension be classified (besides primary and secondary) ?

Answer 6

Based on systolic and diastolic ranges.

Pre-Hypertension (not technically hypertension)
Stage 1 Hypertension (mild)
Stage 2 Hypertension (moderate)
Severe Hypertension (severe)

Question 7

Define stage 1 hypertension.

Answer 7

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

Question 8

Define stage 2 hypertension.

Answer 8

Clinic BP is 160/100mmHg or higher and subsequent ABPM or HPBM daytime average is 150/95mmHg or higher

Question 9

Define hypertension.

Answer 9

Clinical BP is higher than 120/80 mmHg (but lower than values for stage 1)

Question 10

Define severe hypertension.

Answer 10

Clinic systolic BP is 180mmHg or higher or clinic diastolic BP is 110mmHg or higher

Question 11

Why is there no AMBP values associated with severe hypertension ?

Answer 11

Because in severe hypertension, the patient would be admitted to hospital (not sending patient home)

Question 12

Why might a patient be asked to take their own AMBP values in addition to clinic BP ?

Answer 12

Clinic BP can be influenced by the white coat effect

Question 13

Identify possible causes of primary hypertension (the postulated mechanisms).

Answer 13

1) Increase in TPR (increased afterload)
Due to:

– Balance between contraction/relaxation changes (intrinsic in muscle due to increase in excitability)

– Increased sympathetic nerve activity
• Possibly due to psychogenic factors (e.g. stress) or pre-synaptic effects of adrenaline and angiotensin II
• Increased firing rate
• Increase in noradrenaline released

• Triggers release of angiotensin II, which can constrict vessels further (and over time, result in remodelling of vessels)

– Increase in vascular reactivity (i.e. larger than normal response to normal stimulus, or response to lower stimulus than expected). Due to:
• ↑ [Na+] ECF (i.e. increase sensitivity of cells, leading to AP)
• Pathological Na+/K+-ATPase inhibition (Inhibition in kidneys means not removing as much K+, leading to increased fluid retention and increased blood V )
• Damage to endothelium (through alcohol, smoking, increased blood lipid, increased blood sugar)
-↓NO produc tion (NO normally causes dilation, so decrease means constriction)
• Altered blood vessel wall morphology (possibly due to release of angiotensin II)
-↑wall thickness to lumen ratio

Question 14

Identify possible causes of secondary hypertension.

Answer 14

• Renal disease
– altered blood pressure control (altering renal function curve, so not generating as much urine as needed to get BP down. In the long term, desensitize what’s going on in medullary CV control center, allowing system to operate at a higher BP than normal)

• Diabetes
– damaged endothelium (leading to decrease in prod of NO and change in vascular reactivity)

• Endocrine disorders
– Cushing’s, Conn’s, phaeochromocytoma etc.

• Coarctation (narrowing) of the aorta

• Some drugs (Related to hormonal regulation which can feed in regulation of BP. That’s why must check patient’s current drugs before starting hypertension treatment)
– e.g. contraceptive pill, cocaine, amphetamine, NSAIDs, some herbal remedies

• Pregnancy
– eclampsia (convulsions); pre-eclampsia (elevated BP in pregnancy with proteinuria)

Question 15

How does Conn’s disease result in hypertension ?

Answer 15

Adrenal gland tumor, produces too much aldosterone which acts on kidney and cause retention of water, and increase BV

Question 16

What are the risk factors for hypertension ?

Answer 16

• Age(the older you are, the higher the risk)

• Modifiable factors: 
– Exercise
– Diet (high salt; high fat)
– Obesity (especially central obesity) 
– Smoking
– Alcohol intake
– Stress

• Genetic Factors:
– Abnormal inhibition of the Na+/K+-ATPase (Inhibition in kidneys means not removing as much K+, leading to increased fluid retention and increased blood V)
– Family history
– Being of African or Caribbean origin 
– Male

• Psychogenic factors:
– Personality type (stress)

Question 17

What are the effects of hypertension on the body ?

Answer 17

1) Major causes of death associated with hypertension:
• Heart failure (50%)
• Myocardial infarction (20%) 
• Stroke (20%)
• Renal failure (10%)

2) Effects on the Heart
• Heart failure
– pressure overload from ↑TPR leading to LV hypertrophy.
–volume overload due to kidney failure resulting in ↓ac tin-myosin overlap (overfill ventricles, actin and myosin cannot overlap too well)
• LV hypertrophy is a major risk factor for coronary heart disease, dysrhythmias, sudden death and congestive heart failure in patients with hypertension
• Myocardial infarction

3) Effects on the Vasculature
• Accelerated atherosclerosis
– smaller arteries and arterioles (due to need to withstand elevated forces)
• Stroke
– narrowing and sclerosis of small cerebral arteries (due to hypertension); white matter changes
• Retinopathy (untreated, can lead to blindness)
– retinal blood vessels damaged by high pressure
– arteries become narrowed and tortuous
– subsequently veins occluded and oedema and haemorrhage occurs

4) Renal Failure
• Autoregulation tries to protect the glomerulus (and stop huge amount of flow going to kidneys, but in hypertension, want flow to kidneys to get rid of blood V )
• Albuminuria (due to continued high pressure)
• Continued high pressure
– arteriolar walls thicken and narrow
– kidney function declines irreversibly (sclerosis due to fibroblast activity)
• Urine formation falls
– volume overload
– decreased clearance of creatinine, urea and waste products

Question 18

Distinguish between a normal retina and a grade 3 hypertensive retina.

Answer 18

Hypertensive retina has cotton-wool spots and retinal hemorrhages

Question 19

Describe the effects on stage 1 hypertension on the heart, and the kidneys and renal vasculature.

Answer 19

HEART
• Normal size
• ECG normal

VASCULATURE
• Narrowed retinal arteries
• Renal function normal

Question 20

Describe the effects on stage 2 hypertension on the heart, and the kidneys and renal vasculature.

Answer 20

HEART
• Some LV hypertrophy
• Left axis deviation

VASCULATURE
• Retinal vein changes
• Microalbuminuria but renal function ok

Question 21

Describe the effects on stage 3 (severe) hypertension on the heart, and the kidneys and renal vasculature.

Answer 21

HEART
• Marked LV hypertrophy
• ↑left axis devia tion
• Inverted T waves on ECG

VASCULATURE
• Retinal edema/ hemorrhage
• Marked albuminuria
• Falling creatinine clearance

Question 22

What are the effects of stage 1, 2, and 3 hypertension on life expectancy (of a 35 year old male) ?

Answer 22

STAGE 1
Life expectancy: 38-40 years

STAGE 2
Life expectancy: 15-20 years

STAGE 3
Life expectancy: 8-10 years

In general, each 2mmHg rise in systolic blood pressure is associated with increased risk of mortality:
• 7% from heart disease
• 10% from stroke

Question 23

What increase in systolic blood pressure is associated with increased risk of mortality ? What is the cause of this mortality ?

Answer 23

Each 2mmHg rise in systolic blood pressure associated with increased risk of mortality:
• 7% from heart disease
• 10% from stroke

Question 24

Describe the care pathway for hypertension.

may represent it as a diagram

Answer 24

For full diagram, refer to slide 24 in lecture on “Pathophysiology of Hypertension”

If Stage 1 hypertension ⇨ Offer Lifestyle Interventions ⇨ Offer patient education and interventions to support adherence to treatment ⇨ Offer annual review of care to monitor blood pressure, provide support and discuss lifestyle, symptoms and medication

UNLESS, target organ damage present or 10-year cardiovascular risk > 20%, in which case
Stage 1 hypertension ⇨ Offer antihypertensive drug treatment ⇨ Offer Lifestyle Interventions ⇨ Offer patient education and interventions to support adherence to treatment ⇨ Offer annual review of care to monitor blood pressure, provide support and discuss lifestyle, symptoms and medication

ALSO UNLESS patient is under 40 years old, in which case
Stage 1 hypertension ⇨ Consider specialist referral ⇨ Offer Lifestyle Interventions ⇨ Offer patient education and interventions to support adherence to treatment ⇨ Offer annual review of care to monitor blood pressure, provide support and discuss lifestyle, symptoms and medication

If Stage 2 or 3 Hypertension then
Stage 2/3 Hypertension ⇨ Offer antihypertensive drug treatment ⇨ Offer Lifestyle Interventions ⇨ Offer patient education and interventions to support adherence to treatment ⇨ Offer annual review of care to monitor blood pressure, provide support and discuss lifestyle, symptoms and medication

Question 25

Identify possible “modifiable” lifestyle interventions.

Answer 25

• ↓ alcohol intake (<14 units per week)
• Stop smoking
• Healthy calorie controlled diet
• ↓weight if overweight
• ↓ Na+ intake to < 6g salt per day (2.4g or 100mmol of sodium)
• ↑ fruit and vegetable intake (K+)
• ↑ aerobic exercise
• Avoid excessive caffeine rich drinks
• Stress reduction / Relaxation techniques

Question 26

Describe antihypertensive drug treatment.

Answer 26

For full diagram, refer to slide 26 of lecture on “Pathophysiology of Hypertension”

A= ACE inhibitor or low- cost angiotensin II receptor blocker (ARB)
C= Calcium-channel blocker (CCB)
D= Thiazide-like diuretic

For patients under the age of 55:

• Step 1: Start with A
• Step 2: If that doesn’t work, A + C
• Step 3: If that doesn’t work, A + C + D
• Step 4: If that doesn’t work (resistant hypertension), A + C + D + consider further diuretic or alpha- or beta-blocker. Also, consider seeking expert advice

For patients over the age of 55 years or black person of African or Caribbean family origin of any age:

• Step 1: Start with C
• Step 2: If that doesn’t work, A + C
• Step 3: If that doesn’t work, A + C + D
• Step 4: If that doesn’t work (resistant hypertension), A + C + D + consider further diuretic or alpha- or beta-blocker. Also, consider seeking expert advice

Question 27

What is a normal BP range ?

Answer 27

90 to 120 systolic

60 to 80 diastolic