L19 Flashcards by Hayley 1234

Even in a normal diet you still eat more Na then you need therefore you execrate it

Homeostasis of Na is important for many things what is an important reason

maintaining BP

when it is not maintained properly blood pressure (is usually high because of high Na diet) which leads to cardiovascular disease

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why is high BP known as the silent killer

Blood pressure is the silent killer as it causes heart attack, renal disease

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Na is maintained at a very narrow range.

what is the intra and extracellular conc of Na and why is it important that these are maintained

extracellular fluid at about 150mmoles of Na

intracellular at 10mmoles

Na is involved in many cellular functions therefore it needs to be maintained so that cellular processes can run as normal

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maintaining a diet rich in fruits and vegetables can decrease BP by how much

8-15mmHg

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what is normal BP, high BP and low BP

n = 120/80

low = 90/50

high = 180/110

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do athletes tend to have high or low BP

low

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what are sources of Na

your diet

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how you you loos Na from the body

sweat ect (how much mM)

Sweat - 20 to 50 mmol/day

Faeces - 5 to 10 mmol/day

Urine - few to 500 mmol/day

Vomit, diarrhea, menstruation

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decribe the aim of Na homeostasis

the nephrons are responsible for..

Daily Na+ Gain = Daily Na+ Loss

net loss and gain = 0

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how do the nephrons handle the filtered load of Na

Because of the various transporters in the apical and basolateral membranes of the nephron

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what segments of the nephron are permeable to Na

• Proximal Tubule
– Convoluted
– Straight

• Thin and Thick
Ascending Loop of
Henle

• Distal Tubule
– Early
– Late

• Collecting Duct

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which parts of the nephron are NOT permeable to Na

thin descending limb

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Which of the following statements is TRUE?

A. The extracellular fluid Na+ concentration is 170 mM.

B. Normal blood pressure is 150/90 mm of Hg.

C. If you have a high NaCl diet you will excrete more Na+ than normal.

D. All segments of the Nephron can reabsorb Na+

A. 150mM

B. 120/90mmHg

D. the thin descending limb is impermeable to Na

therefore C is correct

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how much Na does the proximal tubule receive per day

• receive ~27,000 mmol of Na+

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how much Na does the proximal tubule reabsorb per day

• reabsorbs about 2/3 filtered Na+

~18,000 mmol

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what kind of epithelium does the PT contain

• a ‘Leaky’ absorptive epithelium

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how does the PT reabsorb Na

3 transporters

• Na+ coupled transporters (apical membrane) these are forms of secondary active transport

Na+ - glucose cotransporters (SGLT2)

Na+ / H+ exchangers (NHE)

Na+ - amino acid cotransporters

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where is Na+-Glucose Co-Transporter - SGLT2 located

• proximal convoluted tubule

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what is SGLT2 responsible for

• bulk of the glucose reabsorption

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what are the characteristics of SGLT2

low affinity for glucose, but high capacity
1:1 Na+ : glucose stoichiometry (one glucose and one Na)

(electrogenic)

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what is SGLT2 and SGLT1 inhibited by

• inhibited by phloridzin

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how many transmembrane domains do SGLT 1 and 2 have

Big proteins with 14 transmembrane membrane domains

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where is Na+-Glucose Co-Transporter - SGLT1 located

• proximal straight tubule

describe the characteristics of SGLT1

high affinity for glucose; low capacity
reabsorbs the remainder of glucose

• 2:1 Na+ : glucose stoichiometry (2Na for 1 glucose)

(electrogenic)

where does the H+ come from that NHE is pumping out of the cell

Carbonic anhydrase adds CO2 and H2O together to form H+ and HCO3- H+ is used for the NHE pump (apical) Bicarbonate is really important for acid base balance as it is used in the blood to reduce acidosis (basolateral)

what is the dominant Na+/H+ exchanger

• NHE3 is the dominant apical membrane isoform

what NHE do we need to know about (theres 4)

* NHE3 is the dominant apical membrane isoform | * also NHE1, NHE2, NHE4 in kidney

what is the role of NHE

* moves Na+ down concentration gradient for exchange of H+ up concentration gradient * also used in pH balance

Which of the following statements is FALSE? A. The Proximal tubule is the ‘powerhouse’ of the Nephron. B. 100% of filtered glucose is reabsorbed by the SGLT2 and SGLT1 of the Proximal tubule cells. C. If you have a high NaCl diet you will excrete more Na+ than a person who has a NaCl normal. D. SGLT2 has a higher affinity for glucose than SGLT1.

D is false (should be the other way around)

how much Na does the thick and thin ascending limbs of henle receive per day

• ~ 8,900 mmol of Na+ is received by the Loops of Henle each day C2)

how much Na does the thick and thin ascending limbs of henle reabsorb per day

• thin and thick ascending limbs reabsorb about 25% (~ 6,750 mmol) of the total filtered Na+

what transporter is used to reabsorbed Na in the thick and thin ascending limbs

• Na+-K+-2Cl- cotransporter (NKCC2)

what is the role of the thick ascending limb of henle

The overall function is to create polarity so that NA, K, Ca and Mg is reabsorbed

where is NKCC2 located

• apical membrane location in the thin and thick ascending limbs

what is NKCC2 doing to Na, K and Cl

• requires Na+, K+, and 2Cl- to function • Na+ and Cl- move down concentration gradient; K+ moves against its gradient

what is NKCC2 inhibited by

• selectively inhibited by ‘loop diuretics’ bumetanide and frusemide Different versions of these inhibitors have been modified to have an even greater effect

why would you want to inhibit NKCC2

For blood pressure regulation

how much Na does the distal tubules receive per day

• ~ 2,150 mmol of Na+ is received by the distal tubules each day

describe the characteristics of the distal tubule for Na reabsorption

* early distal tubule has transport function similar to the Thick AL of the Loop of Henle (NCCT) * late distal tubule has transport function similar to the collecting duct (ENaC)

how much Na does the distal tubule reabsorb per day

• distal tubules reabsorb ~1,350 mmol of daily filtered Na+ (~ 5%)

what channels are responsible for the Na reabsorption in the early and late distal tubule

* Na+-Cl- cotransporter (NCCT) – early distal tubule | * Na+ channels (ENaC) – late distal tubule (and collecting duct)

where is the NA/Cl cotransporter (NCC) located

• apical membrane location in early DT

NKCC2 and NCC are very molecularly similar. what % similar are they

• 60% molecular similarity to NKCC2

what is NCC inhibited by

• inhibited by thiazide diuretics

what cotransporter is Goodman's syndrome associated with

NCC

Which of the following statements is TRUE? A. Cells of the Thin and Thick Ascending Loops of Henle reabsorb 30% of the filtered Na+. B. The Na+-Cl- cotransporter is the main transport protein that secretes NaCl by the Thin/Thick Ascending Limbs. C. The Na+-K+-2Cl- cotransporter is inhibited by thiazide diuretics. D. The cells of the Distal Tubule reabsorb 5% of the filtered Na+.

A. 25% B. reabsorbs C. NCC is inhibited by thiazide diuretics. NKCC is inhibited by loop diuretics D is correct

Collecting Ducts – ‘fine-tuning’ of Na+ how much Na do they receive per day

• receive ~ 800 mmol of daily Na+ filtered

what epithelia does the CD contain

• ‘Tight’ absorptive epithelium

how much Na does the CD reabsorb per day

• reabsorb about ~ 2.5% of the filtered Na+ | ~ 700 mmol

how does the CD reabsorb Na

• Apical Epithelial Na+ channel (ENaC)

what is ENaC blacked by

blocked by amiloride (< 1 µmol/L)

the collecting duct has 2 different cell types what are these, which contains ENaC and what is the role of the 2 cells

principal cell contains ENaC and is responsible for Na and K balance intercalated cell is for pH balance

describe the composition of ENaC

composed of 3 subunits (1a : 1b : 1g) • each subunit - 2 transmembrane domains • each subunit has a large extracellular loop ENaC has proline rich domains

what is the motif of ENaC

• PY motif (PPPXY) - proline (P) - tyrosine (Y) is important in protein-protein interactions, - (X) is another amino acid

what is ENaC regulated by

• regulated by aldosterone

what is liddle's syndrome

• Liddle`s syndrome - gain of function due to mutations of COOH- termini of beta and gamma subunits of ENaC – Too many ENaC channels = too much reabsorption = hypertension

what is Pseudohypoaldosteronism Type I

Pseudohypoaldosteronism Type I is a loss of function due to a mutation of the NH2- terminus of the a subunit – Too few ENaC channels therefore not enough reabsorption