5. Essentials of Renal Physiology Pt. III Flashcards
K in Body Fluids
- Normal serum [K] is ____ to 5 meq/L
- Extracellular K is not bound and is freely ____.
- Normal intracellular [K is ____ to 150 meq/L• ____ orders of magnitude difference
3.5
filterable
120
2
The Nernst Equation Cares
- Cell membranes from excitable tissues are more permeable to ____ than Na or Cl.
- Therefore, the resting membrane potential Em is given by the Nernst’ equation:
Em =-RTln[K]i =-61.5log[K]i =-80to-90mV F [K]e [K]e
3. Since [K]i is relatively constant, small changes in [K]e will have large changes in \_\_\_\_ and dramatic consequences in \_\_\_\_ rhythm and neuromuscular function. • K is the major determinant of resting potential of cells • Cause EC gradient > chemoelectrical gradient ○ \_\_\_\_ gradient is first thing that happens § Differing cxn of K+ on side to another ○ The positive charges from K+ very rapidly builds up + charge on one side that pushes back \_\_\_\_ on the concenrtration gradient ○ Electrical charge exits on diff scale of cxn vs normal cxn that we talked about • K+ is the only one where there is a permeability in the d\_\_\_\_ state ○ Other oions have huge cxn gradient (Na+, Cl-), don't have permebalityt in the resitng state ○ Determines the resting state of excitable cells § Low K outside the cell > make the few K+ go down concentration gradient, and make a molar polarized cell □ Hypokalemia ® \_\_\_\_ the cell ® Opposite happens with hyperkalemia (less K+ crosses, cell is more \_\_\_\_) □ Either abnormalities > lethal on the heart ® Cardiac arrhythmia ◊ Low K+ state > hyperpolarized > makes volt-channels more \_\_\_\_ > increases the risk for lethal tachyarrhythmia
K
Em
cardiac
conc equally resting hyperpolarize depolarized excitable
• Depolarize past threshold > voltage-gated channels open > create ____ to other ions (Na+, Ca++) > further depolarizes the cell > channels have a time-limit and then close > permeability goes away > open up voltage K+ channels > return the cell back to it’s resting potential > ____
perms
overshoot
Potassium
• Input – \_\_\_\_ (oranges, bananas, potatoes, tomatoes) • Output – \_\_\_\_, Renal • Shift (Can have a BIG impact)
* Kidney is regulated; \_\_\_\_ is not * Shift of K+ in or out of cells will have a large impact on extracellular K+ cxn
food
GI
gut
• In and out is the ____ amount
○ Any shift in the ECF, and the ICF > ____ deal
same
big
Major Site Of Regulation of Potassium Excretion:
• The ____
cortical collecting tubule
Cortical collecting duct: principal cells
• Enac > allows Na+ to go in by itself > net \_\_\_\_ charge in lumen ○ Inhiibted by \_\_\_\_ • K+ channel > allows K+ to go out > pulled out by net \_\_\_\_ charge • Whole system stimualted by \_\_\_\_
-
amiliodarione
-
aldosterone
Potassium - Output
• To adequately excrete potassium via the kidneys you need 3 components:
- ____ (ie, enough nephrons working)
- ____ at the cortical collecting tubule
- ____
Absence of any of the above can lead to ____• GFR
○ Nephrons working
• Urine flow with Na+ in it at the CCT
○ Cannot have resorbeda lot before urine got ot the CCT
• CCT swithced on by aldosterone
• Can lead to hyperkalemia in the setting of ____ K+, or cells ____ DOWN THINGS
GFR
urine flow
aldosterone
hyperkalemia
ingesting
breaking
Elevation of both #2 and #3 can lead to K ____
• Elevate both the urine flow and ALD > wasting K+ at the site of the CCT ○ These two things never go in same direction § High \_\_\_\_ diet > flow of urine and amount of Na+ will increase □ ALD will be \_\_\_\_ □ These two are working in \_\_\_\_ directions § Salt restricted diet □ Volume \_\_\_\_ □ ALD will be \_\_\_\_ □ Proximal resoprtion of Na+ will be high > urine flow at last segment of nephron will be \_\_\_\_
wasting salt low opposite deplete high low
• High ALD and high urine
○ Diuretics
§ If block Na+ resorption ____ to distal nephrone/collecting duct > K+ ____
□ Hypokalemia
® Not everyone gets it because they ____ so much K+ > they keep up with their losses
• [???]
proximal
wasting
eat
Potassium Shift
Shift INTO cells • \_\_\_\_ • Beta-agonists (like albuterol) • \_\_\_\_ • Hypo-osmolarity (acute)
Shift OUT OF cells
• ____ due to fasting (generally mild effect)
• Hyperchloremic Metoabolic Acidosis
• ____ (acute)
• Cell rupture (rhabdomyolysis, hemolysis)
• Insulin is most clinically important; big part of treatment for \_\_\_\_ ○ Shifts K+ into cells • Cell rupture ○ Breaking down ○ Hematoma being reaborbed
insulin
hypo-osmolarity
insulinopenia
hyperosmolarity
hyperkalemia
• Changes in EKG as hyperkalemic
○ Peaked ____ wave
• Can cause letahl ____ and can stop heart
○ Hyperkalemia puts volt gated cells in state where cannot ____
• Open heart surgery > stop heart > the way they stop is via big dose of K+ IV
• Lethal injections > K+
T
arrythmia
open
Treatment of Hyperkalemia
Step 1: Stabilize cardiac cell membranes
-____ or calcium chloride
Step 2: SHIFT potassium back into cells
-____ (usually given with D50 to prevent hypoglycemia)
-Albuterol
-____
Step 3: Get it OUT
-____ (if kidneys working) -Sodium polystyrene sulfate (kayexalate) -____ (f kidneys not working)
• Stabilize the cell membranes ○ Having high EC \_\_\_\_++ decreases impact of hyperkalemia • Most impotant acute therapy is INSULIN ○ Rapidly casues K+ to go into cell, and if normal blood sugar and give \_\_\_\_ § Want to avoid acute hypoglycemia • Step 1/2 are temporizing manuevers > will give time, but will not remove K+ from the body • Diuretics can act proximilaly in nephrone > K+ wasting ○ In patients who are not volume deplete > give a \_\_\_\_ ○ If hypovolumeic > give \_\_\_\_, and then add a loop diuretic in ○ K+ binders > SPS > bind K+ in the \_\_\_\_ § Resin that binds K+ ○ If kidneys aren't working > dilaysis
calcium gluconate
insulin
sodium bicarbonate
fursosemide
dialysis
Ca
loop
saline
gut
Treatment of Hypokalemia
• Give ____
• (but don’t give too much too ____) • ‘Nuff said
* Give K+ too fast > cardioplegic > deadly * Slow > challenge to those who are losing a lot of K+ due to diarrhea
potassium
fast
Why Do We Care?
• [H+] is very ____ regulated
• H+ ions are small; they associate closely with proteins and alter their function
• [H+] is regulated on a ____ scale – Normal is 40nM (pH 7.4)
– Range compatible with life is ____ nM
(pH 7.8- 6.8)
• Small > allows to get close ot proteins and affect function ○ Proteins feel presence of protons acutely • Up until now, everything has been on the mM scale (1000th), and now we're on nM (billionth) ○ Huge difference in cxn • Narrow range compatible with life because in nM!
tightly
nanomolar
15-150
pH: A Stupid Unit Invented to Deal With All the Zero’s
• pH = -log[H+] • Acid: substance that increases [H+] – Lowers pH • Base: substance that decreases [H+] – Increases pH
• The unit is not \_\_\_\_; going from .1 change is different ○ Going from 7.0 to 7.1 > different change than from 7.1 to 7.2 because it's a log scale
proportional
- Most acid > ____ (2.0)
* Anything below ____ > lowest a human can survive; and once above ____ inconsistent with life
stomach contents
- 6
- 8
Challenge For The Body
• [H+] is on nanomolar scale
• Normal diet and metabolism adds ____ of H+ to the body
– 1 millimole = 1 million nanomoles
millimoles
cahllenge for the body
• Nm scale of ph, add/sbstatct acid on mM scale ○ Diet is 10 mM of acid per day > need to have kidney excrete 70 mM of H+ per day to stay in steady state ○ Kreb cycle generating CO2 > make 15,000 mM per day § Every CO2 is a potential acid ○ A lot of acid generated in something that must be \_\_\_\_ and fixed
low
HA H++A-
• Buffers require a ____ (HA) and a ____ (A- )
• Acid and base loads are handled by changing between these two forms to prevent large changes in free [H+]
* Add acid to system > excess anion > can bind the acid and drive equil to the left > no free proton that can assoc to protein * If opposite > lose proton > equil to right > donate a proton to the system
hydrogen donor
hydrogen acceptor
Characteristics of an Ideal Buffer
- In sufficient quantity, that it can “absorb” the acid-base load and keep the pH ____ over a wide range of potential insults
- The ____ (base) and donating pair in the buffer are in approximately equal quantity
- The ____ of your acid base pair should be near your ideal pH• Add acid, pH is dropped a lttle, but most is bound by buffer until you run out and then you drop very quickly
stable
acceptor
pKa
BODY BUFFERS
• ECF buffers – \_\_\_\_/carbonic acid/CO2 • H+ + HCO3– H2CO3 CO2 + H2O – Plasma proteins – Inorganic \_\_\_\_
• ICF buffers
– ____ (red blood cells)
– Proteins
– Inorganic____
• ____ (potentially very large buffer reservoir)
– Releases NaHCO3, KHCO3, CaCO3, CaHPO4 in response to acid load
– Accounts for up to ____% of acute acid/base buffering
• CO2 is in equil with bicarb and a. Proton • Buffers inside cells • Bone is a large buffer ○ HA in bone does a lot of buffering • Only know about bicarb buffer system ○ The others are dificult to measure
bicarbonate phosphate hemoglobi phosphate bone 40
• ____ very unstable > impossible to find because changes between the two states
○ Often left out when describing the equilibrium
• Carbonic anhydrase
○ ____ (PCT) and cytosoloic forms
• The bicarb is present on chem 7
○ Measure every single day ebcasue its importantt acid base balalnce
H2CO2
luminal
• \_\_\_\_ is how the CO2 is measured ○ Not same as \_\_\_\_ CO2 ○ Must multiply by factor to get dissolved • Normal pH of 7.4 • Do not memorize equation/do math
pCO2
dissolved
HCO3–/H2CO3 Buffer System
Why is it so important?
- One component (____) is tightly regulated by the kidneys
- The other component (CO2) is independently regulated by the ____ (i.e., it is an “open” buffer system—the solution containing the buffer equilibrates with the environment)
- ____ measured
- Most ____ extracellular buffer• Has features that aren’t present in other buffer systems
• Impact by two organ systems
○ Two safety valves
• Bicarb
○ Regualted by the kidneys (resorbing, and also generate)
• CO2
○ Regualted by the lungs
§ Rate in which breathe > determiend by the need to get rid of CO2
• Creates an open buffer system > in equil with the outside world > makes buffer more ____
• Easily measure because can measure stuff in blood
HCO3- lung easily abundant powerful
• A liter of fluid that has a PCO2 40mmHg (normal); HCO3 24 (normal); and a normal pH
• If removed the buffers (no bicarb)
○ The pH would be ____
2
