Kidney Function III- Regulation Osmolality + Blood Volume

• how is intracellular calcium concentration kept at 0.001mM?

  intracellular calcium movement occurs via calcium-binding proteins (calbindins).
• what is intracellular free/ionised calcium concentration?

  0.001mM
• Describe the processes of Ca, Mg and P reabsorption.

  
• What does calcitriol do?

  Upregulates calcium sensing receptor on chief cells of parathyroid gland & promotes Ca2+ & phosphate absorption in gut.

  -> This affects bone & teeth mineralisation and a deficiency of this can lead to periodontal disease
• What happens when free Ca2+ plasma becomes <1mM?

  It stimulates PTH (parathyroid hormone) release which acts on the kidney & promotes:

  1. Phosphate excretion into the urine

  2. Vitamin D2 & D3 hydroxylation to active form

  (active form of vitamin D3 called calcitriol)

  3. Calcium reabsorption in the kidney
• What is the total calcium concentration in the plasma?

  2.1-2.55mM

  - 45% of which is protein bound

  - 5% complexes with other ions

  - 50% is Ionised calcium (free calcium): 1.0-1.25mM
• what does Calcitonin do?

  This is a hormone produced by the thyroid gland and opposes

  the action of parathyroid hormone
• what does vitamin D do?

  This is the active form of vitamin D3 (1,25 dihydroxycholecalciferol), which promotes calcium and phosphate absorption from the gut as a principal action
• what does Parathyroid hormone do?

  This is a protein produced by the parathyroid gland;

  it promotes renal phosphate excretion, calcium reabsorption and vitamin D production
• What 3 hormones regulate the movement of calcium between bone, kidney and intestine?

  1. Parathyroid hormone

  2. Vitamin D

  3. Calcitonin
• What are the actions of ANP & BNP?

  
• What are the 2 types of natriuretic peptides?

  A type (ANP)- secreted from atrial myocardium

  B type (BNP)- secreted from ventricular myocardium
• What do cells in the cardiac myocardium synthesise and secrete?

  Natriuretic peptides when the heart is stretched due to high blood volume which is caused by an excess of sodium in the body.
• what do low plasma concentration of angiotensin II do?

  • angiotensin II (8-peptide) binds to tubule angiotensin II type 2 receptors and vasoconstricts ONLY renal efferent arterioles and increases GFR.

  An increase in GFR will cause a greater excretion of salt and water and decrease blood volume/pressure.

  
  

  -> this mediated response is: Pressure natriuresis and diuresis
• how does angiotensin II (8-peptide) stimulate vasoconstriction of small arterioles?


  • angiotensin II (8-peptide) binds to arteriole angiotensin II type 1 receptors and causes vasoconstriction of small arterioles which increases BP.

  
  

  -> it causes Vasoconstriction of both afferent and efferent renal arterioles reduces GFR.

  A reduction in GFR will decrease sodium and water excretion and conserve blood volume/pressure.
• which has quicker action, aldosterone or ADH?

  ADH A
• as well as angiotensin II, what can also cause aldosterone release?

  increased plasma K+ concentration
• how does angiotensin II (8-peptide) stimulate Aldosterone secretion?

  • angiotensin II (8-peptide) stimulates the release of Aldosterone from the adrenal context of the adrenal glands (found above the kidney) by the zona glomerulosa

  • aldosterone is released into the blood and increases sodium reabsorption in the distal tubule and the principal cells of the collecting duct (and in the sweat glands, salivary glands and gut)

  • This leads to osmoregulation (it increases the ECFV when it has decrease, therefore it is now restored)
• how does angiotensin II (8-peptide) stimulate ADH release and cause thirst?

  • angiotensin II (8-peptide) binds to angiotensin II receptors in the brain which stimulates ADH release and water reabsorption and causes thirst.
• how does angiotensin II (8-peptide) stimulate proximal tubule Na+ reabsorption?

  • angiotensin II (8-peptide) binds to AT1 receptors

  • once bound, it activates the Phosphoinositol secondary messenger

  • this stimulates the sodium hydrogen exchanger and the sodium potassium ATPase pump on the proximal tubules membranes

  • this causes proximal tubule Na+ reabsorption from the tubules into the blood
• explain the the renin-angiotensin-aldosterone cascade

  • when renin concentration is increased, it causes the conversion of plasma angiotensinogen to angiotensin I (10-peptide)

  • a plasma-converting enzyme converts angiotensin I (10-peptide) to angiotensin II (8-peptide).

  •angiotensin II (8-peptide) stimulates:

  - proximal tubule Na+ reabsorption

  - ADH release

  - Aldosterone secretion

  - thirst

  - vasoconstriction of small arterioles
• give examples of effector pathways that control sodium reabsorption

  • Renin/angiotensin II/aldosterone

  (stimulate Na+ reabsorption)

  
  

  • Direct pressure effect on kidney

  (stimulate renin release)

  
  

  • Renal sympathetic nerves

  (stimulate renin release)

  
  

  • Natriuretic Peptide

  (causes natriuresis, inhibits Na+ reabsorption)
• how does the sympathetic system control renin release?

  Sympathetic nerves of granular cells receive signals from

  baroreceptors (they detect low BP and activate the sympathetic nerves to release renin into the blood of the renal afferent arterioles
• what is renin?


  an important enzyme that controls sodium reabsorption
• where is the renin secreted?

  renin is secreted into the blood of the renal afferent arteriole from the juxtaglomerular cells of the juxtaglomerular apparatus
• explain how intrarenal baroreceptors (granular juxtaglomerular cells) control renin release?


  They respond to reductions in wall tension (stretch) in renal afferent arteriole (intrarenal baroreceptor)

  -> a drop in mean or pulse pressure increases renin secretion
• explain how tubuloglomerular feedback controls renin release?

  Increased NaCl delivery to the macula densa will lead to an increased formation rate of adenosine (ADO), which through A1 receptors causes an increase in calcium in the granular juxtaglomerular cells.

  This inhibits RENIN release
• what extrinsic mechanisms control renin secretion?

  the sympathetic nervous system.
• what causes renin release?

  - ↓ sodium delivery to macula dense

  - ↓ wall tension in renal afferent arteriole

  - ↑ sympathetic activity in response to low BP
• what intrinsic mechanisms control renin secretion?

  - tubuloglomerular feedback

  - intrarenal baroreceptors.
• how do sensors control sodium reabsorption?

  sensors affect renin or natriuretic peptide secretion

  
  

  examples of sensors:

  • in the Macula densa.

  • Intrarenal baroreceptors= granular juxtaglomerular cells

  - High pressure baroreceptors in the central arterial tree.

  - Low pressure baroreceptors in cardiopulmonary circuit

  • Natriuretic peptide secreting muscle cells of the cardiac atria and ventricles
• what 2 regulatory pathways can control sodium reabsorption?

  - sensors

  - effector pathways
• extrinsic control:

  what happens when there is low blood pressure?


  neural control:

  Baroreceptors in carotid sinus and aortic arch cause activation of sympathetic nervous system which:

  - Vasoconstricts renal afferent arteriole ↓ GFR.

  - Reduces surface area of filtration barrier via mesangial cells ↓ GFR.

  
  

  hormonal control:

  - Increases angiotensin II plasma concentration ↓ GFR.

  - Reduces natriuretic peptide secretion ↓ GFR

  
  

  -> overall the ↓ in GFR will conserve sodium and water and maintain BV and BP
• what does the Extrinsic control for GFR do?


  (EXTERNAL to the kidney)

  - maintains ARTERIAL blood pressure by controlling GFR

  (this is done via neural and hormonal input)
• how does the Tubuloglomerular feedback control afferent arteriole constriction?

  Increased NaCl delivery (filtrate flow x concentration) to the macula densa will lead to an increased formation rate of adenosine which through A1 receptors causes an

  increase in calcium in the vascular smooth muscle (VSM) cells. This will cause renal afferent arteriole vasoconstriction and a reduction in GFR.
• how does the myogenic response control afferent arteriole constriction?

  protects the glomerular capillaries from short-term fluctuations in arterial BP by stabilising glomerular capillary blood flow and GFR.

  
  

  -stretch-activated calcium channels in smooth muscle cell membranes open and calcium enters

  - this causes voltage-gated calcium channels to open

  - calcium influx results in a reflex contraction of smooth muscle (vasoconstriction), decreasing the diameter of the afferent arteriole.

  - the vasoconstriction will blunt changes in glomerular capillary blood flow and GFR.
• what are the mechanisms involved in autoregulation within the kidney?

  -Myogenic response.

  -Tubuloglomerular feedback
• what is autoregulation in intrinsic control for the GFR?

  it is the control of afferent arteriole constriction
• intrinsic control of GFR is not perfect. RBF and GFR do change as the arterial blood pressure varies.

  TRUE/FALSE

  TRUE
• when is intrinsic control of GFR absent?

  when arterial pressure is less than 90mmHg