The fluid which enters the Loop of Henle has a ___ osmolarity.
The fluid which leaves the Loop of Henle has a ___ osmolarity.
entering - low osmolarity
leaving - still a low osmolarity, but ADH sorts that in distal tubules and collecting duct
Tubular fluid becomes highly concentrated in the Loop of Henle to set up the cortico-medullary concentration gradient and then becomes less concentrated again as it leaves
What is the osmolarity of the interstitium of the renal cortex?
300 mosmol/L
same as most of the body
What is the concentration gradient going from the renal cortex to medulla?
Increasing
(300 - 1200 mosmol/L)
As fluid goes down the collecting ducts, the osmolarity of the interstitium around it (increases / decreases).
osmolarity increases
So the water from the fluid moves to the interstitium, increasing fluid osmolarity
Leading to the production of a low volume of hypertonic urine
Where do the distal tubules drain?
Collecting ducts
What occurs in the distal tubules and collecting ducts?
Water balance
Ion balance
What regulates the absorption of ions and water in the distal tubules and collecting ducts?
Hormones
What hormones regulate water and ion reabsorption in the distal tubules and collecting ducts?
ADH
Aldosterone
ANP
PTH
What does ADH cause?
Increased water reabsorption
What does aldosterone cause?
Increased SODIUM REABSORPTION
Increased K+ and H+ secretion
What does ANP cause?
Decreased sodium reabsorption
opposite of aldosterone
What affects the permeability of the distal tubules to water?
[ADH]
In the absence of ADH, the permeability of the distal tubules to water is ___.
low
How does the early distal tubule absorb ions?
Triple transporter
How does the late distal tubule reabsorb ions?
Action of ALDOSTERONE (Na+) and PTH (Ca2+)
In the basal state, how permeable is the early collecting duct to ions?
Impermeable
Which gland produces ADH?
Hypothalamus
stored and secreted by posterior pituitary
Which ion triggers __cytosis of peptide hormones from cells?
Ca2+ dependent exocytosis
What is the half life of ADH?
10 - 15 minutes
When is ADH released by the posterior pituitary?
Reduced blood volume e.g dehydration, haemorrhage, sepsis
Which vessels have ADH receptors?
Which type of receptor are they?
Distal tubules
Late collecting ducts
G-protein coupled receptors
What is produced by G-protein-coupled ADH receptors when they are activated?
What does this cause in the apical membrane of the distal tubule and late collecting duct?
Cyclic AMP
Opening of aquaporins
Reabsorption of water
What is ADH also known as?
Vasopressin
The movement of water through ___ of the distal tubules and late collecting duct creates what between the tubules and capillaries?
aquaporins
osmotic gradient
High levels of ADH lead to the production of ___ urine.
Low levels of ADH lead to the production of ___ urine.
hypertonic / concentrated
hypotonic / dilute
As water is reabsorbed, the osmolarity of tubular fluid ___.
increases
Is the ascending limb of the Loop of Henle permeable to water?
No
NaCl only
In high concentrations of ADH, the distal tubules and collecting ducts are ___ to water.
permeable
In low concentrations of ADH, the distal tubule and collecting ducts are ___ to water.
impermeable
Why does fluid leaving the Loop of Henle always have a low osmolarity?
Corticomedullary concentration gradient, loses all its salt as it travels back up, reducing its osmolarity
Remember ascending limb is impermeable to water so osmosis INTO the ascending limb doesn’t occur to reduce the osmolarity
What are the Loop of Henle and ADH’s roles in the production of hypertonic urine?
Loop of Henle creates corticomedullary concentration gradient, but tubular fluid LEAVES loop with a low osmolarity again (because of the gradient)
ADH then alters permeability to water to increase/decrease fluid’s osmolarity as it travels back down into medulla
Usually producing hypertonic urine
Does ADH affect the reabsorption of salt?
No, water only
Which part of the brain detects the water content of the blood?
Hypothalamus
What changes does the hypothalamus trigger in response to dehydration?
Increased secretion of ADH
Increased sensation of thirst
In which situations may a low blood water content cause the hypothalamus to increase ADH secretion and thirst?
Inadequate fluid intake
Haemorrhage
Profuse vomiting
Sepsis (leaky vessels)
Hypovolaemia causes a decrease in systemic ___ ___, which is detected by ___ ___ in the left atrium.
What does this cause?
decreased systemic blood pressure
stretch receptors
Increased ADH production
What genetic disease is caused by low ADH secretion or abnormal receptor response to ADH?
Diabetes inspidus
Low ADH secreiton - central DI
Resistance / abnormal receptors - nephrogenic DI
What are the symptoms of diabetes insipidus?
Large volumes of dilute urine
Extreme thirst
Apart from genetic causes, what may cause central diabetes insipidus?
Pituitary problems
e.g tumour, haemorrhage
How is diabetes insipidus treated?
ADH replacement
Desmopressin
What drug can cause diabetes insipidus?
Which type of the disease?
Lithium
Nephrogenic diabetes insipidus
Which two receptors can detect the conditions which trigger ADH secretion?
Osmoreceptors in the hypothalamus - detect decreased [water]blood
Stretch receptors in the atria - detect decreased atrial stretch
Which type of receptors are found in the GI tract and inhibit ADH secretion in response to ingestion of fluid?
What type of mechanism is this?
Stretch receptors
Feedforward mechanism - because the change is happening in anticipation of increased [water]blood
Which substance inhibits ADH secretion?
Alcohol
What happens to fluid osmolarity in the
a) proximal tubules
b) descending Loop of Henle
c) ascending Loop of Henle
d) distal tubules and collecting ducts with high ADH levels
e) “” with low ADH levels
a) Stays the same (water and salt reabsorption at same rate)
b) Increases
c) Decreases back to 300 mosmol/L
d) Increases (as water is being reabsorbed)
e) Decreases (as water isn’t reabsorbed and some salt will be reabsorbed)
Where is aldosterone secreted?
Zona glomerulosa of adrenal cortex
In what conditions is aldosterone secreted?
1. Decrease in [Na+], stimulating RAAS
2. Increase in [K+], directly stimulating cells
What is the action of aldosterone?
Increases Na+ reabsorption
Increases K+ and H+ secretion
What are the effects of aldosterone on
a) K+
b) Na+
c) H+?
a) Increases K+ secretion
b) Increases Na+ reabsorption
c) Increase H+ secretion
Concentration of which ion is closely related to blood pressure?
Na+
How does aldosterone increase blood pressure?
Increases Na+ reabsorption
Causing an increase in BP, because water follows sodium
Where is most K+ reabsorbed?
Proximal tubules
90% of potassium
Aldosterone is responsible for the absorption of what proportion of potassium?
10%
What electrolyte changes cause aldosterone secretion?
Decrease in sodium (indirectly, by RAAS)
Increase in potassium
Which substance acts on the adrenal cortex to cause the secretion of aldosterone in RAAS?
Angiotensin II
How do
a) aldosterone
b) angiotensin II
increase blood pressure?
a) Increased Na+ reabsorption, vasoconstriction
b) Vasoconstriction, thirst
Which conditions cause renin release by the granular cells of the juxtaglomerular apparatus?
Renal hypoperfusion (as in hypotension or renal artery stenosis)
Decrease in tubular NaCl concentration
Sympathetic stimulation
three different mechanisms
Aldosterone increases the expression of which channels in the renal tubules?
Na+ transporter on apical membrane
NaKATPase on basolateral membrane
Why does heart failure cause fluid retention and oedema?
Reduced renal perfusion
Increase in renin secretion
Increased reabsorption of Na+ and water
Increased blood volume (exacerbating heart failure)
What hormone is held in heart muscle and is secreted when stretch of muscle increases?
What does it do?
Why might muscle stretch increase?
Atrial natriuretic peptide
Decreases Na+ reabsorption, increasing water loss, causing decrease in blood volume
Hypervolaemia (so corrects this)
What are three effects of ANP?
Decreases Na+ reabsorption
VasoDILATION of afferent arterioles in glomeruli
Decreases sympathetic input
What is micturation?
Urination
Which reflex causes involuntary urination?
Micturation reflex
What triggers the micturation reflex?
Which autonomic nerves are involved in the contraction of the detrusor muscle?
Stretch of bladder wall
Parasympathetic
Can the micturation reflex be resisted?
Yes
Increased atrial stretch causes the secretion of which hormone?
ANP
Decreased atrial stretch causes the secretion of which hormone?
ADH