Hypertension and the kidney

Question 1

State the formula for BP.

Answer 1

BP = CO x TPR

where CO = SV x HR

Question 2

Identify the main ways in which the kidney affects BP.

Answer 2

1) Blood Volume (which affects SV, thereby affecting CO)
- Fall in GFR results in increased ECF V
- (Sympathetic activation), and R/A/A system, increase salt reabsorption, which increases ECF V

2) Arteriolar radius (which affects TPR)
-(Sympathetic activation), and R/A/A system, result in vasoconstriction
(-Endothelin result in vasoconstriction)
-Renal prostaglandins (and other vasodilators) decrease vasoconstriction

Question 3

Explaining how the R/A/A system contributes to regulating BP.

Answer 3

Renin is a proteolytic enzyme released from the juxtaglomerular cells of the kidneys in response to sympathetic nerve activation (mediated by baroreceptor feedback), renal artery hypotension (independent of baroreceptor feedback), and decreased sodium in kidney distal tubule.

Renin binds to angitensinogen (in liver, since veinous blood from both kidneys and liver will mix) and converts it to angiotensin 1 → Blood will be going to pulmonary circulation and coming into contact with ACE enzyme which converts Angiotensin 1 into Angiotensin 2

Angiotensin II:
1) acts on resistance vessels to cause vasoconstriction – ↑ total peripheral resistance (so high TPR, high BP if uncontrolled)
2) causes release of aldosterone from the adrenal glands
– ↑ Na+ and water reabsorption (so high BV, high SV, high BP if uncontrolled)
3) stimulates release of ADH from pituitary (increased water retention) (so high BV, high SV, high BP if uncontrolled)

Question 4

Does kidney disease beacause hyperT or is it the other way around ?

Answer 4

May work in both ways, hypertension can be a cause (through damage to arterioles and ischaemia) and result (through volume retention and vasoconstriction) of renal disease.

Question 5

Identify examples of renal disease which are more likely to be associated with hyperT.

Answer 5

Glomerulonephritides (hypertension is more marked and happens earlier in their course)

Question 6

Why do people with kidney disease get high blood pressure ?

Answer 6

Two main mechanisms:

1) ACTIVATION OF RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM

2) RETENTION OF SALT AND WATER WITH REDUCED EXCRETORY FUNCTION
In later stages of renal disease, the latter mechanism become dominant, and high blood pressure is often volume dependent

Question 7

Define hypertension.

Answer 7

State of elevated arterial BP.

Question 8

What are the main causes of hypertension ?

Answer 8

1) Primary hypertension (idiopathic) unknown origin
>90% of cases

2) Secondary hypertension known cause
<10% of cases
-Renal disease
-Coarctation (narrowing) of the aorta
-Endocrine disorders
a) Cushing’s (excess cortisol) (characterised by moon face, buffalo hump, truncal obesity)
b) Conn’s (Excessive aldosterone, adenoma Conn syndrome, hyperplasia)
c) Pheochromocytoma (causes very variable BP)

Question 9

Identify the main possible stages of hyperT.

Answer 9

Stage 1 hypertension:
-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

Stage 2 hypertension
-Clinic BP is 160/100mmHg or higher and subsequent ABPM or HPBM daytime average is 150/95mmHg or higher

Severe hypertension
-Clinic systolic BP is 180mmHg or higher or clinic diastolic BP is 110mmHg or higher

Question 10

What proportion of the adult population has hyperT in the UK ? of those over 60 ?

Answer 10

25% of the adult population in the UK have hypertension

50% of those over 60 years have hypertension

Question 11

How many people worldwide have hyperT ?

Answer 11

1.2 billion individuals worldwide

Question 12

What are the main causes of morbidity from hyperT ?

Answer 12

Stroke
Myocardial infarction 
Heart failure
Chronic kidney disease 
Cognitive decline (dementia)

Question 13

Each 2 mmHg rise in systolic blood pressure is associated with how much increased risk of mortality ?

Answer 13

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

Question 14

State whether the following increases or decreases BP.

• Age
• Sex
• Circadian rhythm
• BMI
• Physical activity
• Stress
• K+ intake
• Na+ intake

Answer 14

Age: Increases
Sex: Male higher BP
Circadian rhythm: Decreases
Body mass index (BMI): Increases
Physical activity: Decreases
Stress: Increases
Potassium intake: Decreases
Sodium intake: Increases

Question 15

Identify the main risk factors for hyperT.

Answer 15

Non-modifiable ones:
Family history

Modifiable ones: 
Obesity
Excessive alcohol
Physical inactivity
Sodium intake

Iatrogenic ones:
Oral contraceptive pill
NSAIDs
Steroids

Question 16

Explain the pathophysiology of hyperT.

Answer 16

Complex disease, multifactorial. Exact pathogenesis still not fully defined, but one hypothesis:

• Primary problem is abnormal salt retention in the kidney: reabsorption of too much sodium
• ECF volume expansion (as water follows sodium)
• Volume receptors – naturetic hormone release (upon V expansion)
• Acts on smooth muscle to cause vasoconstriction and an increase in TPR

Question 17

What is the main criteria for diagnosing hyperT ?

Answer 17

If the clinic blood pressure is 140/90 mmHg or higher, offer ambulatory blood pressure monitoring (ABPM) to confirm the diagnosis of hypertension (helps monitor long term BP + helps avoid possible white coat effect).

‘When using the following to confirm diagnosis, ensure:
1) ABPM
– at least two measurements per hour during the person’s usual waking hours, average of at least 14 measurements to confirm diagnosis

2) HBPM
– two consecutive seated measurements, at least 1 minute apart – blood pressure is recorded twice a day for at least 4 days and preferably for a week
– measurements on the first day are discarded
–average value of all remaining is used’

Question 18

Why must we assess cardiovascular risk and target organ damage in hyperT ? How is this done ?

Answer 18

♦ ‘Use a formal estimation of cardiovascular risk to discuss prognosis and healthcare options with people with hypertension’.

♦ For all people with hypertension offer to:
– test urine for presence of protein (if significant, sign of glomerulus damage, possibly GN)
– take blood to measure glucose, electrolytes, creatinine,
estimated glomerular filtration rate and cholesterol (because CV risk factor)
– examine fundi for hypertensive retinopathy
– arrange a 12-lead ECG’

Question 19

Identify the main effects of hypertension on the body.

Answer 19

1) Mortality
From: 
-Heart failure 
-Myocardial infarction 
-Stroke
-Renal failure

2) Effects on the heart
a) Heart failure
• pressure overload from ↑TPR, LV hypertrophy
• volume overload due to kidney failure; ↓actin-myosin overlap
b) LV hypertrophy is a major risk factor for coronary heart disease, dysrhythmias, sudden death and congestive heart failure
c) Myocardial infarction

3) Vasculature
a) Accelerated atherosclerosis
• smaller arteries and arterioles
b) Stroke
• narrowing and sclerosis of small cerebral arteries; white
matter changes
c) Retinopathy
• retinal blood vessels damaged by high pressure
• arteries become narrowed and tortuous
• subsequently veins occluded and oedema and haemorrhage occurs
• Cotton-wool spots is another sign of damage

4) Kidneys
♦ Albuminuria (due to glomerular damage)
♦ 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 20

Describe any defence mechanisms the kidney may have against damage due to hyperT.

Answer 20

Autoregulation tries to protect the glomerulus (For a range of mean BP, blood flow to kidney and GFR remain stable. Without that, kidney damaged with small increase in BP. But that only works to a point, then end up with damages)