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87 Cards in this Set

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Distribution of Na
-40% in the bone [Not Available for Metabolic Processes]

-ECF (1/3): 140 mEq/L *15L = 2100mEq
-ICF (2/3): 10 mEq/L * 30L = 300 mEq

Therefore, nearly 90% of available Na is in the ECF.
How to estimate body osmolality?
just multiply [Na] * 2!
What happens during Na intake?
Na intake --> increase in [Na]plasma --> increase in osmolality. [AND INCREASE IN GFR!!]

This leads to:
1. thirst for water intake
2. water moving from ICF into ECF
3. ADH secretion to stimulate water retention

***Note that by increasing Na in the body, this ALWAYS leads to an increase in BV***
What detects changes in body Na
- central great arterial vessels
- cardiac atria
- afferent arterioles (intrarenal baroreceptor that releases renin!)
What is ECV
effective circulating volume.

it means "how much stretch is actually being sensed by the baroreceptors?"
CHF:

what happens to ECV, ECF, PV, and CO?
since heart is damaged, CO decreases --> ECV decreases --> ECF and PV increasing!
Water Immersion:

what happens to ECV, ECF, PV, and CO?
immersion compresses the veins which leads to an increase in VR and CO --> increase in ECV.

the body thinks that PV has gone up but really nothing has changed!

***This is why you have to pee in the water***
AV Fistula:

what happens to ECV, ECF, PV, and CO?
by creating the fistula, BP decreases since you are decreasing TPR.

thus ECV briefly decreases --> so that CO increases --> increase in PV and ECF since all the extra CO is bypassing the capillaries
Hepatic Cirrhosis:

what happens to ECV, ECF, PV, and CO?
here fluid accumulates in the splanchnic circulation. also many AV fistulas appear which leads to an increase in CO, a decrease in ECV, and increase in PV and ECF
How to measure Excreted Na
Excreted Na = Filtered Na - Reabsorbed Na

Filtered Na = Pna * GFR ~ 140 mEq/L *180 L/day = 25000 mEq/day!!

Hard to measure reabsorption
Where does Na reabsorption occur?
Proximally (PT and TAL): large capacity. can alter transport in response to load (load dependent)

Distally (DT and CD): limited capacity. used for fine tuning
What happens during Na Loss?
Pna decreases --> ECF (ECV) decreases --> BP decreases.

this activates baroreceptors to stimulate the SNS.

SNS --> leads to renal arterial constriction --> decrease GFR --> decrease in excretion of Na
What can regulate GFR in response to changes in ECF volume
SNS: stimulating renal constriction to decrease GFR

AII: produced due to renin secretion and SNS activity

ANP: released when BV increases by atrial myocytes. INCREASES GFR to oppose an increase in BV

NO: produced by vascular endothelium in response to high ECF. also can dilate renal vasculature and increase GFR
Na Reabsorption in the PT
Early: Na/S symport, Na/H antiport
Late: Na/H antiport, Cl/OH antiport

- approx 67% of Na is reabsorbed here
***Adjusted based on ECF. if ECF increases than less is reabsorbed...***
Na reabsorption in the TAL
K/2Cl/Na symport
Na rebasorption in the DT
early: Na/Cl symport
late: leak Na channel [regulated by AMP and Aldo]
Regulation of Na reabsorption at PT:
- SNS: increase stimulates reabsorption
- AII: increase stimulates reabsorption
- NO: inhibits reabsorption
- Starling Forces: if peritubular capillary volume increases (increase ECV), oncotic pressure decreases and so does Na reabsorption
Regulation of Na reabsorption in the TAL
- load dependent!
- ADH stimulates reabsorption
- prostanoids and NO (released when ECF volume increases) inhibits reabsorption
Regulation of Na Reabsorption at the distal tubule
- only responsible for 3% of reabsorption [Still very BIG!!]

- Aldo stimulates reabsorption
- ANP inhibits
- No/prostanoids inhibit
Aldosterone actions
1) Na reabsorption at DT
EARLY
open channels
insert vesicles (Na and ATPases) into membrane
LATE
stimulates Na channel production
stimulates Na/K ATPase production

- activates intercalated alpha channels to stimulate K reabsorption and H secretion
RAAS
Renin-AII-ALdo System

Renin secretion -> AII activation -> Aldo secretion --> Na reabsorption
Renin Secretion and Regulation
- secreted from granular cells in the afferent arteriole

secretion stimulated by:
- increased SNS
- reduced [NaCl] in macula densa
- reduced pressure at the afferent arterioles [intrarenal baroreceptor]

mechanism of release
-PKA pathway activated by NE (from SNS) or PG's that are released from the macula densa
-if renal arterial pressure decreases, renin secretion is stimulated [could be due to myogenic reflex, since intracellluar Ca decreases. and Ca normally inhibits adenylyl cyclase. so by disinhibiting AC, lower Ca can activate renin secretion]

Also can be inhibited by macula densa:
- if [NaCl] is too high, the macula densa releases ATP and adenosine which increase intracellular Ca to cause contraction. this also inadvertantly inhibits renin secretion too!
How to limit Na excretion
if ECF decreases --> BP decreases --> baroreceptors activate SNS --> decrease GFR (and thus decrease NaCL flow at macula densa)...

Both SNS and macula densa stimulate renin secretion --> stimulate RAAS --> stimulate NA retention!
how do AII and SNS affect renal arterioles?
contract BOTH afferent and efferent.

SNS innervates the afferent arterioles and decreases GFR.

while AII in low concentrations constricts mostly efferent arteriole to keep GFR steady. but in higher concentrations, AII also contracts the afferent arteriole!!
Natriuretic Factors effects on Na reabsorption
ANP secretion:
- increases GFR (increase Na excretion)
through dilating the afferent arteriole and constricting the efferent arteriole
- decreases Renin secretion (increase Na excretion)
- decreases Also secretion
- decreases Na reabsorption
- decreases ADH secretion (increase water excretion)

***These are all direct actions***
Distribution of K
most is intracellular

- ECF: 14L * 5mEq/L = 65 mEq (2%)
- ICF: 28L * 150mEq/L = 3500 mEq (98%)

ICF K: muscle ~2600 mEq; bone,RBC,Liver ~ 300 mEq
Normal Plasma K Levels
normal: 3.5 - 5 mEq/L
hypokalemia: <3.5
hyperkalemia: >5
Role of K
- cofactor for enzyme
- regulate muscle blood flow (if it increases, flow increases)
- cell growth
- cell volume
- depolarization and establishing cell membrane potential
Extra-renal K homeostasis
- when you ingest K, usually 30 mEq/day. in ECF, you add 30 mEq/15L = 2 mEq/L.

- 90% go to the urine, 10% go to the stool

- insulin/Epi stimulate K uptake into ICF
- Aldo stimulates K secretion in urine!
Insulin and Epi role in K regulation
they stimulate K uptake into ICF

- activate Na/K ATPases and increase turnover rate.
- insulin is the most important. if there is a deficiency, you would get hyperkalemia, esp after a meal!
- same with administering B2 antagonist since it blocks Epi actions!
how does extra-renal K homeostasis compare with Renal homeostasis?
extra-renal response is much faster!

kidney takes several hours to change K secretion!
non-hormonal factors that alter K homeostasis
- acid/base balance: acidosis leads to hyperkalemia and alkalosis leads to hypokalemia.
***in fact a 0.1 change in pH leads to a 0.6 mEq/L change in Plasma [K].***
THIS IS DUE TO H/K ANTIPORTS IN THE CELLS THAT SUCK UP H AND EXPEL K. AND H INHIBITS NA/K ATPASE

- Exercise: releases K from muscles

- osmolality: if hyperosmotic - cell shrinks and K leaves (due to increased driving force) --> hyperkalemia. opposite occurs with hypoosmolality.

-cell lysis. when the cell lyses, lots of K is expelled and thus leads to hyperkalemia
K regulation by renal system
- K is altogether: filtered, secreted, and reabsorbed.

- 80% of reabsorption occurs in the PCT

- 10% occurs in the TAL

- the rest of the fine tuning occurs in the DT and CD.
function of NO in renal physiology
- produced by tubular cells in PCT to inhibit Na reabsoprtion

- also in the loop of Henle inhibits Na reabsorption (with prostanoids)

- dilates the renal arterioles to increase overall GFR
K regulation in the PCT
- reabsorption occurs secondary to water and diffusion (passively)

- nearly 80% is reabsorbed
K regulation in the TAL
- K/2Cl/Na symport channels are used for K reabsorption.

- also a K/Cl symport in the basolateral membrane

- also leak K channels in the basolateral membrane.

All of these are used for K reabsoprtion.

- 10% total is reabosrbed

**Note there are some leak K channels that eject K back into the lumen but this is minimal!!**
K regulation in the CD
- [LATE DT AND CCD] principal cells: K SECRETION (and Na reabsorption) through leak K and Na channels [By increasing Na reabsorption, you are also increasing K secretion!]

- [MCD] intercalated cells (alpha-type): REABSORBS K. uses ATP-powered K/H antiport luminally and leak K channels basolaterally.
Na conservation vs K conservation
Na conservation is 10x better... 0.1% excreted vs 1% excreted.
How does Renal handling of K change according to Diet?
normal diet: from PCT to urine, nearly 95% is reabsorbed

low K: nearly 99% is rebasorbed

High K: nearly 200% is excreted!! (can excrete >100%!!)
How does hyperkalemia alter K secretion?
- stimulates Na/K ATPase
- increaes luminal K permability
- induces aldosterone
How does aldosterone alter K secretion
- stimulates Na/K activity
- stimulates luminal Na and K permeability
LONG
- makes proteins and transporters
How does Tubular Flow alter K excretion
- increase flow enhances K secretion
this is because K becomes more diluted so there is a steeper electrochemical gradient

also because the Na/K Pump is more activated as flow increases so the cell becomes more depolarized

also cilia in distal CD bend and release Ca this opens K channels.
acid-base balance on k regulation
alkalosis - stimulates K excretion
acidosis - inhibits K excretion ( inhibits the Na/K ATPase)
How to counteract K secretion
1) if ECF decreases --> AII increases --> Aldo increases --> K secretion increases

but AII also increases proximal absorption and thus decreases distal flow. this opposes K secretion.

2) if ADH increases --> stimulates K secretion. BUT also increases distal absorption and thus decreases distal flow. this inhibits K secretion!

3) if you are acidotic. this decreases K secretion. BUT it also decreases proximal reabsorption and thus increases distal flow. this increases K secretion!!
filtration barrier

so what can pass through easily?
- endothelium (fenestrated)
- basement membrane (negative charge)
- podocytes (slits)

- Basically anything small and positively charged can pass through easily
JGA (juxtaglomerular apparatus)
3 components
- macula densa (distal tubule)
- granular cells (afferent and some efferent arterioles
- extraglomerular mesangial cells
fx of extraglomerular mesangial cells
regulates RBF and GFR
filtration process
- involves starling forces
- very low resistance in glomerulus so there is a very small drop in pressure
- depending on the resistance of the afferent and efferent arterioles, the glomerular pressure will change
how does arterioles affect glomerular pressure
- if afferent arteriole constricts, than glomerular pressure will fall
- if efferent arteriole constricts than glomerular pressure will rise
RPF
renal plasma flow

- can change from RBF using the hematocrit (RBF * (1-hematocrit) = RPF)

- usually 20% of RPF is filtered on average
normal RBF
usually about 1/4 of CO which is 1.2 L / min
how to calculate GFR
GFR = RPF * FF (filtration fraction)

usually RPF = 660 ml/min and FF = 0.2

so GFR is usually 130 mL/min or 180 L/day
how do the different pressures change throughout the glomerulus
- oncotic pressure increases since fluid passes into bowmans and [protein] rises

- hydrostatic pressure decreases insignficantly

THEREFORE FILTRATION IS GREATER AT THE AFFERENT ARTERIOLE THAN THE EFFERENT
where along te glomerulus is filtration the greatest?
greater at the afferent than the efferent due to changes in the oncotic pressure
filtration equilibrium
event where oncotic pressure equals hydrostatic pressure and no filtration occurs.

- does not occur in human physiology
How to calculate filtered load
Fx = Px * GFR
how to calculate excreted load
Ex = Ux * Vurine
clearance
how much of a molecule is cleared from the blood (excreted) per minute

- Cx = (Ux * Vurine) / Px
special characteristic of inulin
inulin is only filtrated and neither reabsorbed nor secreted

- thus Finulin = Einulin

- thus Clearance of inulin = GFR!!
special characteristic of PAH
- all PAH is completely cleared from blood in a single pass through the kidney at low enough RPF

- so Cpah = RPF
body pH equation
pH = 6.1 + log [HCO3]/(0.03*pCO2)
how are different elements of body acid controlled?
pCO2 is controlled by respiratory
HCO3 is controlled by kidneys
sources of acid
respiration (volatile acid)
fixed-acid production (non-volatile acid)
how does the body buffer acids
50/50 in ECF/ICF

- ECF is done with HCO3
- ICF is done with proteins and phosphates
elements of renal acid/base response
- there is HCO3 recovery from filtration
- also HCO3 production from the loss when buffering fixed acids

This is all done by secreting and excreting H+
HCO3 reabsorption at the PCT
- 80% of total HCO3 is reabsorbed here

- does so through secreting H
2 ways: Na/H antiport or H ATPase

- this increases CO2 levels. CO2 diffuses into the cell and is broken back into HCo3 and H.

- the HCO3 is reabsorbed in 2 ways basolaterally:
Na/3HCO3 symport
HCo3/Cl antiport (late)

H is sent back out to bring back another HCO3

**Note that the Tubular Fluid pH does not change much**
HCO3 transport at the distal nephron
- intercalated alpha: secretes H+
**10% of HCO3 reabsorbed here
**luminal: uses H/K ATPase or H ATPase
**Basolateral: Cl/HCO3 antiport and Cl leaks back out

- intercalated Beta: secretes HCO3
**useful during alkalosis
**luminal: HCo3/Cl antiport
**basolateral: H ATPase
how is the pH in the collecting duct
- pH is usually low at around 4.4
how to make NEW HCO3
- excrete H+ with a new buffer (HPO4 or SO4)
**1/3 of H+ secretion
**Prompt but LIMITED

- also use ammonium (NH4)
** 2/3 of H secretion
**Flexible, but is delayed response, requiring enzyme synthesis
Phosphate Buffers
pKa of phosphate is around 6.8.

the HPO4/H2PO4 ratio changes across the tubule.
- at the beginning the ratio is 0.01.
- at the end, the ratio is 4
ammonium for H secretion
break down glutamine into 2NH4 and 2 HCO3 in the PCT epithelium

to get rid of NH4 secrete using Na/NH4 antiport. or NH3 can diffuse.

- at the TAL the Na/K/2Cl transporter can also transport NH4 into the interstitium. the NH4 gets converted to NH3 and then diffuses into the CD to form NH4 again and then it is trapped.
Renal Response to acidification and Mechanism
- Reabsorption of all filtered bicarbonate
- Increased excretion of hydrogen with TA (titrated acids)
- Increased production of ammonium

Mechanisms:
- changes in tubular cell pH
- regulation of transporter expression
- enzyme synthesis
how to keep GFR and glomerular blood flow constant during normal physiological conditions
- myogenic response
- tubuloglomerular feedback
TGF
tubulo-glomerular feedback

- when tubular flow increases (as a result of increased GFR), the macula densa senses this and releases adenosine and ATP.

the adenosine activates A1 receptors which are vasoconstrictors (unlike A2 receptors in the CVS which are vasodilators)
how to regulate TGF sensitivity
- volume contraction INCREASES TGF sensitivity

- volume expansion DECREASES TGF sensitivity
endothelin
produced by endothelial and mesangial cells and is a potent vasoconstrictor of afferent and efferent arterioles
luminal glucose transporters
-SGLT1: high-affinity/low capacity 2Na:1Glu [LATE PT]

-SGLT2: low-affinity/high capacity 1Na:1Glu [EARLY PT]
how is water reabsorption different at:

- PCT
- Loop of Henle and early DT
- Late DT and CD
- PCT: 2/3 reabsorbed isoosmotically

- Loop of Henle: usually 23% through osmotic driving force. ascending is impermebale to water. descending is permeable

- DT and CD is regulated by ADH. with ADH, large reabsorption and steeper osmotic gradient
G-T Balance
a state where Na filtration and H2O filtration must remain constant. so if Na and H2O filtration were to increase, their reabsorption must increase too!!

- accomplished through Starling Forces at peritubular capillaries: increase GFR at constant RBF would lead to increase in oncotic pressure in capillaries and an increase in reabsorption!

- another way is through filtered load of glucose, AA's... since these need Na to be reabsorbed. as long as they are below Tm (usually are...) any increase in their load will increase reabsorption
ADH actions
- increase H2O permeability at the CCD and inner MCD

- increase Na and Cl and K reabsoprotion in TAL (stimulates the transporter)

- increases IMCD permebailtiy to urea allowing for urea recycling

- constricts vase recta capillaries to reduce flow and keep interstitial osmolality high!
mechanism of ADH
V2 receptor activates PKA pathway to activate AQP2 synthesis
single effect
pumps can only maintain a gradient of 200 mOsm in the loop of henle
what occurs in the thin ascending limb of henle
passive NaCl reabsorption occurs occurs secondary to urea.

- although both tubular and interstitial osmolality is 1200, tubular Na is 1000 and interstital Na is 600!. so Na effluxes into interstitium as urea enters tubule!
why does the maximum osmolality in the loop of henle decrease during diuresis?
- since there is no ADH, the Na/K/2CL transporters in the TAL are not activated as much and less salt is reabsorbed and thus the osmlality is a little higher in the tubule

- lack of ADH also limits urea reabsorbtion so there is less urea in the interstitium and lower osmolality

- also the lack of ADH means that the vasa recta capillaries in the medulla are more dilated and have higher flow and thus carry away salts much faster. this keep the interstitial osmolality much lower
urea recycling
- PCT: 50% is reabsorbed as it follows H2O
- in the CD, theres a high [urea] sue to H2O reabsorption. and urea permeability in IMCD is regulated by ADH.

- with ADH, urea leaves the CD and is recycled into the interstitium and the vasa recta. there it leaks back into the DT and goes back to the IMCD.

- this keeps medullary interstitial osmolality very high.
why do ppl with a low protein diet have trouble conserving H2O?
less urea! with less urea, there is less recycling and the medullary intersitital osmolality is lower! and thus water reabsiorption is lower!
how does inflow of vasa recta compare to outflow
ouflow > inflow because lots of H2O is absorbed as it passes through the medulla.