lecture 6 Flashcards
sodium
most prevalent and important solute in ECF
effect of high Na+
retain more water so weight increases
high Na+ intake in diet
increased osmolarity (body won’t allow), so increased ECF volume, (increased water reabsorption) increasing blood volume and pressure
where is Na+ reabsorbed
65% proximal (to aid in reabsorbing other nutrients), 25% thick ascending loop of Henle (create hyper-osmolar fluid), 8% distal, 2% collecting
if high GFR
increase Na reabsorption as more fluid in; if low, lower Na reabsorption; always reabsorbing same proportion
change amount of Na excreted
change amount put in tubular system (by chaning pressure and GFR)
if low BP
increased sympathetic activity (also stimulates granular cells for renin so ang II to reduce BP and Na+ uptake in PCT) and reduced GFR; PCT reabsorb more Na+; sympathetic causes aldosterone release increasing Na+ uptake in distal and collecting duct; if low tubular Na+ at juxtaglomerular apparatus, renin produced
if high BP
atrial naturietic peptide, suppresses activity so decreases Na reabsorption
JGA of kidney
produces renin due to Na+/K+/Cl- channel. amount of Na+ in goes down, so low osmolarity vs environment so water leaves cells, shrinking them and they produce NO and PGE2 - stimulate granular cells to secrete renin
RAAS
liver - angiotensinogen - angiotensin I (renin) - angiotensin II (ACE in lung - greater epithelial SA; causes vasoconstriction) - aldosterone (adrenal) - feeds back to kidney for Na+ and water reabsorption
effects of ang II
proximal: increase Na+ and water reabsorption, increasing ECF and BP; vascular: vasoconstriction and increased BP; causes aldosterone synthesis
aldosterone
works on principal cells of collecting duct, stimulares Na+ absorption, K+ and H+ secretion; excess causes hypokalaemic alkalosis
how does aldosterone work
induces expression of apical Na channel of collecting duct; induces formation of Na+/K+ ATPase pumps by increasing transcription of corresponding mRNA; Na+ reabsorbed into blood and K+ secreted
hypoaldosteronism
reduced Na reabsorption in distal, increasing urinary Na loss; ECF volume falls, increasing renin angII and ADH; causes dizziness, low BP, salt craving and palpitations
hyperaldosteronism
increased Na reabsorption in distal, decreasing urinary Na loss; ECF volume rises (high BP), reduced renin angII and ADH; increased ANP and BNP; causes high BP, muscle weakness, polyuria, thirst
Liddle’s syndrome
inherited hypertension as mutation in aldosterone activated Na+ channel (always on), causing Na+ retention and hypertension
reabsorbing water when high Na+, causing polyuria and polydypsia
thirst as higher osmolarity than should have; as more water in, more urine out
baroreceptors
low pressure side: heart (atria, right ventricle), high pressure side: vascular (carotid sinus, aortic arch, JGA)
low pressure side
can respond to low or high BP; if lowm afferent to brainstem for sympathetic activity and ADH release; if high pressure, atrial stretch so ANP, BNP released
high pressure side
slide 29
atrial natriuretic peptide (ANP)
small made in atria (also make BNP); released in response to atrial stretch
actions of ANP
slide 30
slide 31: high GFR
decent diagram
slide 32: low GFR
another cracking diagram
ACE inhibitors
reduce ang II so reduces vasoconstriction and aldosterone production (less Na+ reabsorption in DCT)
osmotic diuretics
glucose (increases osmolarity in tubular fluid, acting as osmotic component so lesser osmotic gradient - diabetes mellitus), mannitol
need to ensure more solute gets to dct and collecting duct if high BP to get rid of more water
loop, thiazides, K+ sparing (don’t lose as much K+) - slide 36
carbonic anhydrase inhibitors
export H+ at expense of Na+, so if inhibit production of H+ in PCT, so less Na+ can come in, so more Na+ excreted as reaches dct
loop diuretics e.g. furosemide
potent; block triple transporter (Na+/K+/Cl-) in ascending limb of loop of Henle; more Na+ in tubular fluid so less in interstitial space also
thiazides
block Na+/Cl- symporter in dct
K+ sparing diuretics
distal ct; reduce Na+ in from lumen so reduce amount of Na+ pumped out into blood
spiralmalactone (inhibits aldosterone)
inhibits Na+/K+ ATPase to blood and Na+ channel in dct (similar to K+ sparing diuretic)
high K+
depolarises membranes - action potentials, heart arrhythmias; low also causes heart arrhythmias
meal
increase K+ absorption, increase plasma K+, increased tissue uptake quickly (na/k pump) so K+ doesnt rise (stimulated by insulin; reduced by aldosterone and adrenaline)
K+ absorption
30% reaches descending loop of henle; anywhere between 1-80% secreted
k+ secretion
stimulated by high plasma K+, pH, high aldosterone, high tubular flow rate
K+ secetion by principal cells
slide 45
aldosterone stimulates K+ into cell and out into lumen
slide 46
collecting tube cells
cilia so as flow increase, stimulate PDK1 activity, cascade so increases IC Ca2+ - activates K+ channels to release more K+
hypokalaemia
common; diuretics (increases tubular flow rates and K+ excretion), surreptitious vomiting, diarrhoea, genetic mutations (reduced Na+ inport so increased flow rate)
hyperkalaemia
response to K+ sparing diuretics, ACE inhibitors; elderly
