renal 7-10 Flashcards
What is the normal range of plasma osmolality?
- 280-290 mosmol/Kg H₂O (± 3)
- (max. urine osmolality is 1400 mosmol/kg H₂O)
What is ADH, where is it produced and what is its half-life?
- nonapeptide synthesised in supraoptic and paraventricular nuclei (SON and PVN) located in the hypothalamus
- t½ of 15 mins (degraded in liver and kidney)
What does ADH (8-arginine-vasopressin) do and what does this make it?
- increases H₂O permeability of cortical and medullary collecting ducts
- concentrates urine → anti-diuretic
What is diuresis?
Hint - the opposite of anti-diuresis
increased production of urine
What happens to urine with and without ADH?
- w/o ADH, more dilute urine produced
- w/ ADH, less conc. urine produced
What is ADH synthesised within?
Hint - look at the bigger inactive picture
a large precursor molecule (166 AA) → molecule:
[Leader-ADH]-gly-lys-arg-[neurphysin]-arg [Glycopeptide (copeptin)]
To which two locations does ADH move into after its synthesis?
(Hint - S/P → n (pp) → a of hthp tract)
SON/PVN → neurohypophysis (posterior pituitary) → axons of hypothalamohypophyseal tract
What happens to ADH during movement, where is it stored and why?
(Hint - stored in neuro-thing)
- progressively cleaved
- within neurophysin (protein) in nerve terminals
- released into bloodstream when required
What is the primary stimulus for ADH and what is it detected by?
- primary stimulus is change in plasma osmolality
- sensed by osmoreceptors
What are osmoreceptors and what is their threshold for activation?
- a collection of cells located near SON
- threshold for activation 280 mosmol/kg H₂O → small amount of tonic ADH release and linear response if plasma osmolality rises
What type of system is the ADH system and how can this threshold be reset?
- very sensitive system
- reset by other factors i.e. hypovolaemia: hypo-(= low)-vol-(= volume)-emia(= of blood)
State five factors other than plasma osmolality stimuli for ADH release.
(Hint - BP/volume, sickness, BGC, oxygen, tension)
- haemodynamics (BP/volume via baroreceptors) → less sensitive (10-15% change required) but response exponential → hence, drugs affecting BP also affect plasma ADH levels
- nausea → instant and profound body trying to preserve water, plasma ADH increases 100-1000-fold
- hypoglycaemia (modest changes)
- hypoxia (via carotid chemoreceptors)
- angiotensin (increased osmotic response)
What is the mechanism for ADH action? Use the diagram in the notes.
(Hint - ADH via AC via GPs → cA → PKA → A-2 water channels → insert into upper membrane → more water can pass → more water kept → more salty urine)
- principal cells have V₂ receptors on basal membrane for ADH
- ADH activates adenylate cyclase (via G-proteins) → produce cAMP → activates protein kinase A (PKA) → PKA phosphorylates non-functional aquaporin-2 water channels → these channels insert into apical membrane → water permeability increases → water reabsorption → urine concentrates
What does the volume of urine (of a certain concentration) excreted depend on?
(Hint - ADH + n of solute)
- concentrating ability of kidney limited therefore, volume of urine excreted depends on:
• level of circulating ADH
• amount of solute to be excreted
What is the minimum volume of urine which can be excreted?
Hint - a digit of 4 divided by a digit of 7
800/1400 kg H₂O/24 h = 0.571L/24h
If the amount of solute to be excreted in a urine sample is 2000 mosmol/kg H₂O, calculate the min. volume of urine to be excreted to achieve this.
(Hint - where the min. volume of urine which can be excreted is 1400)
2000/1400 = 1.4L
What would happen to the hydration status of a man who drank 1L of 2000 mosmol/kg H₂O solution?
(Hint - would be a loss/gain, miliosmoles + what would be needed?)
- solution of high osmolality would mean gaining a L of fluid
- 2000 milliosmoles = more water would need to be used
Describe the pelvic nerve micturition reflex including the roles of stretch receptors.
(Hint - v of urine → pressure → s. receptors of bladder + pelvic nerve A → pelvic nerve E + IU sphincter → urine urge sent to brain)
volume of urine increases → pressure rises → stretch receptors in bladder activate pelvic nerve afferents → pelvic nerve efferents relax internal urethral sphincter → urge to urinate communicated to higher centres (pons)
(NB: rugae unfold as bladder initially fills so little pressure change)
How does voluntary control in the pelvic nerve micturition reflex occur?
(Hint - done using pons too, pud nerves involved keeping EUS closed, pud nerve activation allows EUS relaxation + urine flow)
- achieved by integration with (pons) via pudendal nerves
- pudendal nerves tonically active → keep external urethral sphincter closed
- voluntary inhibition of pudendal nerve activity relaxes external sphincter allowing micturition
State the events that occur when we deviate from normal osmolality (285mosmol/kg H₂O) due to:
a) water deprivation, solute ingestion, diarrhoea
b) excess fluid digestion
(Hint - effect on ECF osmolality → ADH response towards hypothalamic receptors → CD water permeability → water retention/excretion by kidneys, lateral preop nuclei → thirst and water intake/excretion - NB: ECF osmolality is the reverse of what you think would happen in each situation)
a) increased ECF osmolality, so hypothalamic receptors (supraoptic + paraventricular nuclei):
- ADH release from posterior pituitary → collecting ducts water-permeable → water retention by kidneys → returns to normal (min urine volume 300ml/day)
• lateral preoptic nuclei → thirst → water ingestion → returns to normal
b) decreased ECF osmolality, hypothalamic receptors (supraoptic and paraventricular nuclei):
- ADH release suppressed → collecting ducts water-impermeable → water excretion by kidneys (max. urine volume approx. 23L/day) → returns to normal
• lateral preoptic nuclei → thirst suppressed
Which two things is water excretion regulated by?
Hint - literally by water levels and salt balance
- ECF osmolality (water and salt content regulation)
- Na⁺ balance (major ECF cation)
What response is caused in the body by increased/decreased Na⁺?
(Hint - excess salt it leads to high BP, too little salt means the volumes and pressures of cells are irregular/low)
- excess Na⁺ is a major factor in hypertension
- decreased Na⁺ levels can lead to hypovolaemia and hypotension
How is Na⁺ content restored when there is increased/decreased ECF Na⁺?
(Hint - effect on osmolality → water needs → return to normal osmo and ECF volume)
- increased ECF Na content e.g. NaCl ingestion → increased osmolality → water retention/thirst → normal osmolality + increased ECF volume
- decreased ECF Na content e.g. sweating with only H₂O being replaced → decreased osmolality → water excretion → normal osmolality + decreased ECF volume
How can the amount of Na⁺ reabsorption be modified?
Hint - about the EC circulation and water changes
by changes in ECF (effective circulating fluid) and ECV (effective circulating volume)
What is ECV and what should it not be confused with?
Hint - ECV is not IVCLR
- the component of blood which is perfusing the tissue
- not the same as intravascular (blood) volume e.g. congestive HF can affect CO affecting ECV values
What is renin?
Hint - not a hormone but an active-siter stored in the kidney jug
an enzyme synthesised and stored in juxtaglomerular apparatus of kidneys
State three stimuli for renin release and what they are all reflective of?
(Hint - (1) symp nerves (2) tension AA (3) Na⁺ delivery → decrease in a volume by a change in salt)
- increased sympathetic nerve activity (baroreceptor reflex)
- decreased wall tension in AA
- decreased Na⁺ delivery to macula densa
- all reflective of a decrease in ECV caused by decreased body Na
By which mechanism does renin release from the macula densa occur and via which receptors are sympathetic nerves affected?
(Hint - PG hormone, granular cells and the main enzyme, and the main receptors of your drug monograph)
• macula densa →
- releases prostaglandin I₂ (PGI₂)
- stimulates granular cells to release renin into blood
- sympathetic nerves via β-adrenoreceptors
What are the actions of renin?
‘angio-(=blood vessels)tensin(=tension/BP)’
(Hint - angiotensinogen → atn I (main enzyme) → atn II from which the main action comes from, also pp into decta into octa)
- (acts on p. protein) angiotensinogen → angiotensin I (decapeptide by enzyme ACE) → angiotensin II
- angiotensin II is the primary hormone in Na⁺ regulation (an octapeptide)
How is angiotensin II broken down and into what?
Hint - by pp enzymes into atn 3 + by-products
- by plasma peptidases into:
- angiotensin III + inactive products
What are the effects of the RAAS on:
a) increased BP (Hint - affects salt affecting AA)
b) decreased kidney Na⁺ (Hint - the whole shebang of the RAAS response)
- decreased Na⁺ → afferent arteriole BP decreased
- → angiotensinogen I → angiotensinogen II → angiotensinogen III (broken down into inactive products)
What does the removal of the adrenal glands cause and why?
Hint - you can’t survive w/o it
metabolic defects → death within two weeks because of adrenal insufficiency due to a disease
What are four main effects would removal of the adrenal glands have on the body?
(Hint - (1) loss of salt from urine, (2) EC salt decreases, (3) ECF lessens, (4) circulation topples over)
- loss of NaCl from body via urine
- extracellular Na⁺ content falls
- ECF volume markedly reduced
- circulatory collapse
How can death due to removal of the adrenal glands be avoided?
(Hint - lots of salt and injecting aldo)
high Na⁺ diet and aldosterone administration
What is aldosterone and where is it synthesised?
Hint - a mineral hormone made from the main chol fat, histology GFR the outside layer of adr. gland
- mineralocorticoid (regulates body salts) synthesised from cholesterol
- secreted by zona glomerulosa of adrenal gland
What are the three stimuli for aldosterone release?
Hint - too little salt, too many bananas, too little water
- decrease in plasma Na⁺ concentration → not an important stimulus under normal conditions
- increase in plasma K⁺ concentration → very sensitive (small change causes lots of release)
- decrease in ECV → via angiotensin II
What effects does aldosterone have on bodily ion concentrations?
(Hint - keeps salt, gets rid of banana, gets rid of lemons, promotes salt return in gut and eccrine glands)
- stimulates Na⁺ reabsorption in collecting duct
- stimulates K⁺ secretion in collecting duct
- stimulates H⁺ secretion in collecting duct
- promotes Na⁺ reabsorption in gut and sweat glands
What effect does aldosterone have on ion transport in:
a) principal cells? (Hint - principally 2 positive ions - salt and bananas)
b) intercalated cells? (Hint - CA leaves and normal lemon enters)
a) Na⁺ IN and K⁺ OUT
b) H⁺ IN and HCO₃⁻ OUT
What is ANP?
Hint - 4x7 long, released from A cells when A stretch, act on names receptors in CD, N → promote Na loss
- 28 AA cardiac hormone (from 126 AA prohormone)
- released from atrial cells in response to atrial stretch (hypervolaemia)
- acts at ANP receptors in collecting duct
- natriuretic (promotes Na⁺ loss in urine)
State the mechanism of ANP action.
(Hint - inhibits the pumper and aldo, reduces the main RAAS enzyme release, promotes vasod increasing kidney function measurement G, also note atrial ‘natriuretic’ peptide so this is also a function)
- inhibits collecting duct Na-K ATPase and aldosterone secretion
- reduces renin release (indirectly inhibits aldosterone release)
- promotes vasodilatation of AA (increases GFR)
- ‘natriuretic’ = decrease in Na reabsorption
What is urodilatin?
Hint - ANP replica with a few extra AAs, a natro from kidneys
- a natriuretic originating in kidney
- almost identical to ANP (+4 AAs) + same actions
What is dopamine?
Hint - a natro from the PT, inhibits two forms of Na pump
- natriuretic synthesised in proximal tubule
- inhibits Na-K ATPase and Na-H antiport
