Week 10 Flashcards
Which water compartment is potassium mostly found in
Intracellular fluid (ICF) ~ 98%
How does insulin lead to increased uptake of K+ via Na+/K+ pump?
Insulin binds -> IRS1 -> PI3-K -> PDPK1
-> aPKC (atypical protein kinase C) -> Phosphorylation of Na/K pump -> Increased function/uptake of K+
How does B2-catecholamine lead to increased uptake?
B2-catecholamine -> cAMP -> PKA -> Phosphorylation of Na/K pump
(Standard G-as pathway)
How does acidosis reduce the uptake of K+?
High acidosis -> Low H+ conc gradient -> Less H+ is effluxed out of cell -> Less Na+ uptake into cell
-> Less Na+ uptake = Less Na+ for Na+/K+ pump -> Less K+ uptake into cell
Affect of hypokalemia (outside) in action potentials
Hyperpolarisation happens -> Too much K+ leaks out of the cell
Affect of hyperkalemia (outside) in action potentials
Not enough repolarisation occurs -> Cell membrane is more depolarised
Clinical Consequences for Hypo and Hyperkalemia
Hypo: Difficult in muscle contractions, muscle weakness, promotes cardiac arrhythmias
Hyper: Muscle stiffness and weakness, abnormal ECG, LIFE THREATENING ARRHYTHMIAS
Why would a high-potassium meal not necessarily cause problems?
Many high potassium foods also include high glucose -> Insuline promotes uptake of K+
What happens to potassium when excersizing
Exercising releases K+ out of muscle cells -> Local increase in K+ causes vasodilation -> Extra K+ is redistributed into resting tissue by increased adrenaline
Where is most K+ reabsorbed in the kidney? (2 main locations)
Proximal tubule (60%)
Thick Ascending limb (20~25%)
How is K+ reabsorbed in the proximal tubules?
Paracelullar reabsorption (literally through the gaps of the proximal tubular cells) as water draws the K+ out
How is K+ reabsorbed in the thick ascending limb?
- Paratubular diffusion (same as proximal)
- Na+/K+/2Cl pump
How is potassium recycled within the tubules?
ROMK and Na+/K+/2Cl- pump feeds K+ to each other (ROMK efflux out of tubules, Na+K+2Cl- influx)
How is K+ secreted (concentration) into the cortical collecting duct and why is K+ conc low in the lumen (principle cells)
Na+/K+ transporter keeps intra K+ high and Na+ low -> ROMK and Maxi-K can efflux out K+ ions into the lumen -> Low extracellular K+ conc due to high flow rates in the lumen
How is K+ secreted (electrical gradient) into the collecting duct (principal cells)
When Na+ is reabsorbed by ENaC, lumen is slightly negatively charged -> Allows K+ ions to be attracted to the lumen -> Increases secretion of K+
How does aldosterone increase K+ secretion
Aldosterone produced in response to hyperkalemia -> Diffuses inside cell and boosts transcription of ENaC, ROMK and Maxi-K
EnaC for lumen negativity
How is there balance in K+ concentrations
Low ECF -> Renin/Angiotensin II and aldosterone released -> Low GFR
But low GFR is balanced by high secretion via aldosterone into the collecting duct
vice versa if high ECF
Is urine acidic or alkaline under normal conditions
Should be acid, very rare to excrete basic urine
What are some dietary source of acids
Fatty acids
Amino acids, especially sulfur-containing ones (metabolised to sulfuric acid)
What mmol of H+ does a typical North American diet generate
70
What are the 3 buffers humans use to even out H+ ions
Bicarbonate, Monohydrogen Phosphate (not that important), Ammonia
What happens to H2CO3 and CO2 production when H+ ion rise
H2CO3 decreased as more is turned to Co2 + H2O (equilibrium shifts to right)
Relationship between HCO2 and PCO2
Inverse
How do lungs excrete H+ ions (pathway)
Carotid and Aortic chemoreceptors detect an increase in H+ -> Increase activity to ventilation muscles -> Increase breathing out of Co2 -> Decrease PCO2
How much bicarbonate is filtered by the kidney per day
3750 mmol/L
Where is the main absorption site for bicarbonate
Proximal tubules
How is bicarbonate reabsorbed? (mechanism)
Na+/H+ exchanger imports Na+ and excretes H+ -> Excreted H+ combines with bicarb -> Carbonic Anhydrase 4 (CA4 ) facilitates conversion to CO2 + H2O -> CO2 is diffused back into tubule cell -> CA2 then converts is back to H+ and bicarb -> H+ is then exchanged out by Na+/H+ exchanger -> Na+/Bicarb co-transporter reabsorbs bicarb back into blood
How does the Na+/K+ pump help bicarb reabsorption
Maintaining low intracellular Na+ it allows for more NHE activity (more H+ secreted)
How is bicarbonate regenerated?
Basolateral Glutamine + Luminal Na+/Glutamine transporter increases intracellular glutamine -> Glutamine is converted to aKG (alpha ketoglutarate) and when aKG is converted to malate, it generates bicarb -> Ammonium is also generated, which is excreted out by Na+/H+ Exchanger -> Bicarb is reabsorbed
How is ammonia/ammonium excreted
NHE in the proximal tubule excretes Ammonium ion -> Na+/K+/2Cl transporter influx ammonium into TAL cell -> Na+/H+ exchanger in TAL efflux out into interstitium -> Ammonium enters the collecting duct cell via Rh transpoters -> Ammonia diffuses out of collecting duct cell -> Collecting duct pumps H+ ions -> Ammonia + H+ = Ammonium ion trapping it inside lumen
Which cell in the collecting duct excretes H+ ions?
Intercalated cell *NOT PRINCIPLE
How does the IC cell secrete H+ ions
H+ ATPase transporter
What happens to amino acids in the liver?
Deamination reaction, removing the amine group -> rest of the carbon backbone is converted to urea
*some for energy through the TCA
What is the function of the urea cycle?
Converts ammonia into urea (ammonia is very toxic)
How does urine flow rate dictate urea reabsorption?
High flow rates -> Low reabsorption (flow too fast, low conc gradient)
How does vasopressin regulate urea reabsorption (mechanism)
Vasopressin binds to G-protein receptor -> cAMP, PKA activated -> UT-A1 is phosphorylated -> Increase influx of urea
Relationship between water reabsorption and urea
Since vasopressin dictates both, they correlate with each other, high water reabsorption, high urea reabsorption
Where is erythropoeitin produced?
Kidneys - Perycytes cells in the interstitial compartment of the kidney
How does erythropoeitin work? (mechanism)
Kidney senses hypoxia/low hemoglobin -> Erythropoetin is released -> Stimulates red blood cell maturation in bone marrow ->
Why is there pericytes cells (cells that detect low oxygen and release erythropoietin) in the kidney?
Kidney has a lot of ATP usage, thus oxygen consumption is high (getting used in Na+/K+ pumps)
Where is renin produced
in the kidney (juxtaglomerular)
Vitamin D synthesis (mechanism)
7-dehydrocholesterol -> Vitamin D3 via UV-B light -> Hydroxylated into 25
dihydroxyl Vit D3 (in the liver) -> 1,25 dihydroxyl Vit D3 in the kidneys (Via 1-hydroxylase) (Active form)
Why is vitamin D important?
Calcium stores in bones
Increase calcium and phosphate absorption
Where is 1-alpha hydroxylase located?
Proximal tubule
How does uremia cause edema
The kidney can’t excrete the Na+ and H2O, leading to fluid accumulation in the ECF, causing edema
How does uremia cause low calcium
No active form of vitamin D (1,25 OH Vit D3) is produced, thus low absorption of Ca2+ from the gut, and also pulling Ca2+ from bones. Low Ca2+ causes PTH secretion
How does uremia cause high potassium
- Decreased GFR -> Decreased K+ excretion
- Acidosis will cause more K+ to be excreted out
