Hormonal Control of BP

Question 1

which systems regulate BP? (2)

Answer 1

• fast acting neuronal system (moment to moment regulation: without it = postural hypotension)
• hormonal system

(detected with baroreceptors)

Question 2

where is sensor for the hormonal control of BP?

Answer 2

sensor: juxtaglomerular apparatus of the distal tubule of the kidney

Question 3

which two systems does the juxtaglomerular apparatus of the distal tubule of the kidney control?

Answer 3

• GFR
• hormonal blood pressure

Question 4

what are the three cellular components of the juxtaglomerulus apparatus?

Answer 4

• mesangial cells: between afferent and efferent arteriole

- macula densa cells: wall of the distal tubule

- juxtaglomerular cells: around wall of the afferent and efferent arterioles. outside of tubule but can secrete materials than can go into afferent of efferent arterioel

Question 5

Answer 5

Question 6

what is role of macula densa cells?

Answer 6

• detect electrolytes: particularly Na+ conc in fluid of distal tubule

Question 7

what does it mean if macula dense cells detect low Na+ in distal tubule?

what happens (what is released? from where? x2) as a result of this?

Answer 7

• concentration of sodium in the distal tubule is too low = it means that the glomerular filtration rate (GFR) is too low

- causes prostaglandin E2 (PGE2) from the macula cells be released

• acts on juxtaglomerular cells to release renin in the afferent & efferent arterioles

Question 8

complete the blanks:

1. if Na+ conc too low in the fluid of the …… ….. , is detected by macula densa cells
2. this means that the ….. is too low
3. this causes the release of …. by the macula dense cells
4. consequently, ….. is released from the ….. cells into the afferent and efferent arterioloes

Answer 8

1. if Na+ conc too low in the fluid of the distal tubule is detected by macula densa cells
2. this means that the GFR is too low
3. this causes the release of prostaglandlin E2 (PGE2) by the macula dense cells
4. consequently, renin is released from the juxtaglomerular cells into the afferent and efferent arterioloes

Question 9

explain why low Na conc in distal tubule indicates low GFR?

Answer 9

• in the proximal tubule and loop of Henle sodium is removed from the tubular fluid at a constant rate.
• if the GFR is low, less sodium enters the proximal tubule per minute and so more of this sodium will have been removed by the time the fluid reaches the distal tubule.
• Conversely, if the GFR is high, more sodium enters the proximal tubule per minute and less of this sodium will have been removed from the tubular fluid when it reaches the distal tubule.

So overall: in distal tubule fluid:

low [Na+]= low GFR (low flow rate means more time for Na reabsorption)

High [Na+]=high GFR (high flow rate means less time for Na reabsorption)

Question 10

if Na conc is too low

Question 11

explain the mechanism of tubuloglomerular feedback
(how detected / effect?)

Answer 11

When sodium concentration is low in the distal tubule: (in addition to driving renin release) the macula densa cells also activate a local process called tubuloglomerular feedback.

This process acts via local hormones to produce relaxation of the smooth muscle of the afferent arteriole.

This increases the filtration pressure and brings GFR back to normal.

(GFR depends on difference in pressure between afferent arteriole and efferent arteriole; dilation of afferent arteriole will increase in the pressure in it and thus filtration pressure and thus increase GFR)

Question 12

What are two things that occur as a result of low Na conc in distal tubule?

Answer 12

1. Renin released (after prostaglandlin 2 is released)
2. Tubuloglomerular feedback

Question 13

what is the role of angiotension II?

Answer 13

angiotension II: potentn constrictor of smooth muscle of systemic arterioles - raises afterload and blood pressure

Question 14

explain the mechanism of renin-angiotension-aldosterone system

Answer 14

• low Na + conc in DT causes release of renin from juxtaglomerular cells
• renin enzyme (passes into the venous blood) converts (the globular protein) angiotensinogen secreted by the liver into angiotension I
• angiontension I passes into lungs, further cleaved by angiotension converting enzyme (ACE) into angiotension II
• angiotension II is a potent vasoconstrictor of smooth muscle of systemic arterioles: raises afterload and therefore BP

(increases BP -> increases GFR and Na+ reabsorbtion)

Question 15

how much of the blood plassma is filtered through the glomerulus and how much goes into the efferent ateritole?

Answer 15

20% goes through to glomerulus and is filtered

80% goes through to efferent arteriole

Question 16

angiontension II can have different effects depening on where its receptors are - what are they? (4)

Answer 16

i) proximal tubule: Increases Na+ reabsorbtion, which increases blood flow, which increases BP
ii) adrenal cortex: increases aldosterone, which causes increase Na+ & H20 reabsorbtion in distal tubule, increase bloodflow and BP
iii) systemic arterioles: binds to GPCR = artriolar vasoconstriction = increases BP
iv) brain: stimules release of ADH = increase Na reabsorbtion

Question 17

what are the two subtypes of angiotension II receptors?

Answer 17

• *AT1:**
• *i)** GCPR which increases Ca entry into smooth muscle & constriction to occur
  ii) stimualtes noradrenaline release from sympathetic nerve terminlas (can increase BP via SNS too)
  iii) found in cells of adrenal cortex: secretes aldosterone
• *AT2:**
• subject of current research: has actions in the central nervous system and may be involved in apoptosis (programmed cell death) growth and development of neurones and other tissues.

Question 18

what is the effect of aldosterone after it has been secreted due to activation of AT1 cells?

Answer 18

• acts on Enac channels (Na channels) in the DCT
• increases Na absorbtion: which increases H20 reabsorbtion
• decreases urinary loss of water and Na
• causes an increase in blood volume and therefore blood pressure

Question 19

what is liddle syndrome / disease?

Answer 19

• enac channels undergo ubiquitination
• this causes inappropriately elevated sodium reabsorption in the distal nephron

- this makes have too much water retention and hypertension

Question 20

complete:

atrial natriuretic hormone …. sodium reabsorption. (& … blood volume)?

Aldosterone …. sodium reabsorption (& … blood volume)

Answer 20

atrial natriuretic hormone decreases sodium reabsorption. (& decreases blood volume)

Aldosterone increases sodium reabsorption (& increases blood volume)

Question 21

Answer 21

Note that Renin affects both the blood pressure control system by the effect of AGII on systemic arterioles and also the blood volume control system by the effect of aldosterone on kidney tubules

Question 22

what happens to BP (through RAAS system) when an atheroma is formed in afferent arterioles?

Answer 22

afferent arterioles are narrowed due to atheroma formation, or some other factor which reduces blood flow into the kidney.

This will reduce GFR, more sodium will be absorbed

This will lead to a reduced sodium concentration in the distal tubule.

The JGA cells release renin, which is converted into angiotensin, which will raise blood pressure in an effort by the kidney to maintain GFR.

Question 23

what are the two main types of drugs that interact with angiotension

Answer 23

1. ACE inhibitors: (captopril) block angiotensin converting enzyme and thus prevent formation of Angiotensin II.
2. Angiotensin receptor antagonists (losartan). Block AT1 receptors
3. 4. 5. BUT: Remember, the renin-angiotensin system is a controlled system. The excess renin in a hypertensive individual is being released for a reason. If you give a drug that blocks the actions of angiotensin you may reduce blood pressure but you do not cure the primary problem which may be poor renal perfusion. The kidney may respond to ACE inhibitors by increasing renin output, meaning that you have to keep giving greater and greater doses of the drug to have the same antihypertensive effect.

Question 24

what does renin do in the brain?

Answer 24

• renin causes the release of ADH from the posterior pituitary gland
• decreases urine outpute and preserves body water and plasma

Question 25

what are the 5 main types of anti-hypertenisve drugs & their actions? & SES?

Answer 25

1) Calcium antagonists-
vasodilate
S/E- flushing, oedema.

2) ACE inhibitors-inhibit renin/angiotensin/aldosterone system (RAAS)
-vasodilate
S/E- cough, low BP

3)Angiotensin Receptor Blockers-Block
action of angiotensin II- vasodilate

S/E- Low BP

4) Thiazides
-Salt and water loss
S/E- impotence, hypokalaemia

5) Beta blockers
-Slow & reduce force of heart, reduce renin secretion
S/E –lethargy, bronchospasm

Question 26

is it blood pressure controlled after mild haemorrhage? :)

Answer 26

If you lose blood by a haemorrhage, several things happen:

1. Water moves into the blood from capillaries by osmosis. This minimises the reduction in circulating blood volume but the blood becomes more dilute; sodium concentration is reduced; hyponatraemia occurs (Normal plasma sodium is 140 mmol/L. Hyponatraemia is when plasma Na < 135 mmol/L
2. The sympathetic nervous system constricts veins. Most blood (80+%) is in the veins and capillaries. Constricting the veins can reduce the venous blood volume by the amount of blood lost. So, venous return to the heart and hence cardiac output may be almost unaltered.
3. When the diluted blood passes through the kidneys there is less sodium filtered because its blood concentration is less. Thus, the sodium concentration is decreased the distal tubule, even though the GFR is normal.

This reduced sodium load stimulates renin release in the normal way. The angiotensin that is formed stimulates aldosterone release from the adrenal cortex. The aldosterone increases sodium reabsorption in the distal tubule. Thus, gradually the blood sodium concentration is restored to normal. There will also be ADH release

These mechanisms ensure that small volumes of haemorrhage (<10 % blood volume) are fully compensated for and do not cause a drop-in blood pressure.

Question 27

what is a different way that renin can be released?

describe how positive feedback can occur because of this alternative renin release xx

Answer 27

Renin can also be released by sympathetic stimulation; there are sympathetic nerves to the kidney, and beta receptors on the cells of the juxtaglomerular apparatus.

This raises the possibility of positive feedback; sympathetic stimulation increases renin release, angiotensin then increases noradrenaline release which in turn increases renin release leading to hypertension

Question 28

Answer 28

Question 29

renin controls ? (2)

Answer 29

sodium levels AND blood pressure levels

Question 30

what is hyponatremia?

what can mild hyponatremia cause?

what can severe hyponatremia cause?

Answer 30

hyponatremia:

• *- low blood sodium levels (below 135 mmol / L)** normal Na levels are 135 and 145 mmol / L
• decreases osmotic pressure of plasma: keeps water in the blood
• if low allows plasma to move out of blood into extravascular intersitial space in tissues (because hydrostatic pressure > osmotic pressure - so it leaves the blood capillaires)
• *mild:** loss of energy, fatigue, muscle weakness
• *severe:** rise in intracranial pressure -> vomiting, nauseas headachhes, coma

Question 31

osmotic pressure

hydostatic pressure

Question 32

what is bradykinin and what if effect of angiotension on it?

Answer 32

• bradykinin: 9 amino acid peptire
• ACE inhibitors: increase bradykinin levels by inhibiting its degradation
• causes a dry cough in patients who take ACE inhibitors (why people often stop taking them)
• can cause angioedema - occurs 5x higher in African descent: which is why ACE inhibitors are not the first line of drugs for treating hypertension