3 The renin-angiotensin-aldosterone system Flashcards
Describe what the Juxtaglomerular apparatus is, and its role
It is a structure where afferent arteriole makes contact with DCT (in the nephron of the Kidney)
- Involved in BP regulation
- Found at vascular pole of each renal corpuscle
- Made up of:
> Macula Densa (DCT), Juxtaglomerular (granular) Cells, Extraglomerular mesangial cells
Describe the Macula Densa, and its role
The macula densa is an accumulation of columnar cells within the DCT
- They monitor Na+ concentration in the formation of urine
- Regulate Glomerular Filtration Rate (GFR) and release of Renin from juxtaglomerular (granular) cells
- GFR is also affected by sympathetic nerves directly innervating juxtaglomerular cells
What it Renin
and what is its role?
Renin is a proteolytic enzyme that is synthesised by granular cells (juxtaglomerular cells) in the wall of glomerular afferent arterioles
- Renin cleaves angiotensinogen to angiotensin I
Renin’s function:
- is to raise BP via other mediators
Why is Renin released
- In response to decreased arterial pressure (body acts like low BP is caused by fluid loss) - there are baroreceptors in the afferent arteriole
- Decrease in sodium load to the distal tube (macula densa responds to [Na+])
- Direct stimulation by sympathetic NS
(stress = raised BP)
- This is mediated by B1 adrenergic receptors
Describe what Angiotensin-Converting Enzyme (ACE) is,
and its role
ACE is expressed by many tissues (kidney), but conversion largely occurs during transit through the lungs
ACE:
- convert Angiotensin I to Angiotensin II
hence, ACE inhibitors (ACEi) work to stop this function
Describe the role of Angiotensin II (Ang II)
Has many roles:
- Constrict resistance vessels
- Promote aldosterone release from the adrenal cortex
- Stimulates ADH release from the posterior pituitary gland and stimulates thirst (and others)
Briefly describe what the Adrenal glands are + their actions
Adrenal glands are suprarenal glands (on the kidney), they are endocrine organs (hormone-producing)
- Medulla makes adrenaline, noradrenaline
- Zona glomerulosa (1st layer of cortex) makes mineralocorticoids
- e.g. aldosterone -
Describe what Aldosterone (Aldo) does
Aldosterone targets mostly principal cells in the renal tubule distal segments
- It has multiple actions, all of which promote recovery of Na+ and osmotically obligates water from the tubule (into blood - increasing circulating volume hence the BP rise)
It takes up to 48 hours to work (peak effects)
- This is because aldosterone upregulates the expression of genes encoding Na+ channels and pumps (takes time)
Describe the role of Vasopressin an Anti-diuretic hormone (ADH)
Anti-diuretic hormone (ADH), also known as arginine vasopressin
- is released from the posterior pituitary when tissue osmolality rises OR blood volume decreases
Its principal role is in ECF volume regulation through control of renal water retention
If circulating levels are sufficiently high (e.g. haemorrhage), it can also vasoconstrict
SO, give the overall actions of the Renin-angiotensin-aldosterone system
(assuming BP is too low)
If BP is too low
- It can be detected by baroreceptors in afferent arteriole of the nephron
- Or Na+ decrease can be detected by Macula densa or SNS
- Renin is released by granular cells
- Renin converts Angiotensinogen to angiotensin I
- Angiotensin I is converted to Angiotensin II by Angiotensin Converting Enxyme (ACE)
- Angiotensin II then constricts blood vessels, as well promote the release of aldosterone from the adrenal cortex
(it also stimulates ADH release from the post. pituitary - stimulates thirst) - Aldosterone then promotes the effect of Na+ and the accompanying water, into the blood from the tubule in the kidney (by upregulating the expression of genes for Na+ channels and pumps)
The combined effects of vasoconstriction and increased peripheral resistance + more Na+ and water =
- Corrected (higher) BP
SO, low BP = more renin = higher BP
Describe how many pathologies are associated with high RAA
These can occur chronically and acutely in response to the decrease in blood flow to the kidney.
It can occur physiologically, with normal variations in fluid intake, but can also result from pathological causes:
- Anything that reduces cardiac output (heart failure)
- Renal stenosis or aortic stenosis (narrowing) - produces renin-induced hypertension
- Hypotensive shock
What is hypertension (HTN)
It is an abnormal elevation of systolic and/or diastolic blood pressure
- Repeated BP of 140/90mmHg, confirmed on ambulatory BP reading
Describe secondary hypertension
Secondary hypertension is when a specific cause for hypertension is found,
- so secondary to an underlying disease process (renal disease is seen in 5% of cases)
e.g. primary hyperaldosteronism - too much aldosterone
Describe essential Hypertension
Primary (Essential) hypertension:
- Can be benign (slowly progressive OR
- Malignant (rapid onset + > 180/110)
Aetiology not completely understood - genetic component
e.g. increased prevalence in Afro-Caribbean’s + those with a family history
Describe the activation of the Renin-Angiotensin-Aldosterone (RAAS) system as a cause of Hypertension
The RAAS hormonal system is a key regulator of BP.
Its activation promotes:
- vasoconstriction through Angiotensin II
- Na+ and Water retention through aldosterone
Blood renin concentrations can be elevated in hypertensive patients who are white and aged < 55 years old
- Hence, the justification for treatment for ACEi, or ARB’s
The mechanism appears to be less important in older patients + in Afro-Caribbean patients
- So, ACEi is no longer the 1st treatment
