renal lecture

8/11/2019 Renal Lecture

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Fluid Compartments of the Body

Intracellular space is the space within cellmembranes

Extracellular space is the space between cells(interstitial fluid) and within blood vessels(plasma)

Electrolyte composition (e.g. salt and watercontent) of interstitial fluid and plasma isidentical

Intracellular and Extracellular Space/Fluid

Compartmentalization of BodyFluids

Total body water (TBW)= 60% of body weight 60% x 60kg = 36L

Intracellular water (ICF) = 2/3 of total body water 2/3 x 36L = 24 L

Extracellular water (ECF) = 1/3 of total body water 1/3 x 36L = 12 L

Extracellular Fluid

Plasma water = of extracellular water 1/4 x 12L = 3 L

Interstitial fluid = extracellular water 3/4 x 12L = 9 L

60:40:20 rule


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Osmotic Composition of Major

Fluid Compartments

Osmolarity

Osmoles refers to the number of impermeable particlesdissolved in a solution, regardless of charge. This isimportant for determining the diffusional movementof water.

For substances that maintain their molecular structurewhen they dissolve (e.g. glucose), the osmolarity andthe molarity are essentially the same.

For substances that dissociate when they dissolve, theosmolarity is the number of free particles times themolarity. Thus for a pure NaCl solution, a 1 Molarsolution would be 2 Osmolar (1 for Na, and 1 for Cl).


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osmolarity (Osm) is defined as moles of dissolvedsolute per volume of solution in liters

In human plasma the concentration of dissolved

particles is about 290 X 10-3 M.

Osmotic gradient

Osmotic gradient is required in order to achieve

net water movement between ECF and ICF

Because water can move freely between

compartments, a change in the osmolarity of asingle compartment results in redistribution of

TBW (total body weight) between compartments

(driven by the osmotic gradient) until osmotic

equilibrium is restored.


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Major Function of Kidney:

Homeostasis

Maintain optimal fluid environment inthe body

Regulates H20 - osmolarity NaCl

Most ions Maintains plasma volume = long termregulation of blood pressure

Balance Concept

Net gain must equal net loss if substance remains in asteady state

(e.g. water, salt)

Consumption(Internal gain)

metabolism

(External gain)

food

air

(External loss)

urine

stool

expired air

sweat

Ingestion Production Excretion(Internal loss)

metabolism

++ =


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Water balance

Electrolytes and Water

Salt is not produced or consumed by the

body so balance is maintained by regulating

the amounts excreted in body fluids (urine,

sweat, stool) such that they equal the

amounts ingested (ingestion = excretion)

Kidneys maintain water and salt balance in

the body by regulating output of both in the

urine


6/22

Absorption Mechanisms of Salt

and Water in the Renal Tubule

The glomerulus has a high filtration rate: about180 litres a day

(Glomerular Filtration Rate-GFR)

Sodium is high in the extracellular fluid and lowinside cells (intracellular).

Therefore Na is high in plasma, and whenplasma is filtered by the glomerulus, theresulting filtrate is also high in sodium

Little Na reaches the final urine, so the bulk ofNa, and following water, is absorbed as thefiltrate travels along the renal nephron (tubule)


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Daily Filtered Load of NaDaily Filtered Load of Na++

(>99% of which must be reabsorbed)(>99% of which must be reabsorbed)

Amounts of NaAmounts of Na++ reabsorbed byreabsorbed byvarious segments of the nephronvarious segments of the nephron

GFR=180 L/day

PNa=142 mmol/L

Filtered Load of Na 25,500 mmol/day

700 mmol/day


8/22

Amounts of NaAmounts of Na++ reabsorbed byreabsorbed by

various segments of the nephronvarious segments of the nephronGFR=180 L/day

PNa=142 mmol/L = 1500g salt


700 mmol/day


9/22





17,000 mmol/day67% of filtered load

1Kg

1

33% remaining

Sodium Absorption in Proximal Tubule

SGLT1Sodium GlucoseCotransporter


10/22

Renal tubules have a finite capacity

to reabsorb glucose

If glucose concentrations in the blood exceed

the tubular transport capacity of SGLT

glucose is seen in the urine

Urine test for diabetes glucose stick

Sodium Absorption in Proximal Tubule

SGLT1Sodium GlucoseCotransporter

NHE3Sodium HydrogenExchanger

NaPi2Sodium Phosphate

Cotransporter

AQP1Aquaporin 1


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1Kg

1

33% remaining

Osmolarity of the filtrate has not changed at this point

Osmolarity at end of

proximal tubule:

a) 180 mOsm

b) 142 mOsm

c) 290 mOsm

Answer: ?

NHE3 AQP1

Glomerulus

Proximal tubule

Iso-osmotic movement of Na and water


12/22

Thin Descending Limb

Only H20 transport in this region

Aquaporin-1 present

No Na movement in this segment

NHE3

AQP1

AQP1

Glomerulus

Proximal tubule

Thin Descending

Limb of

Henles Loop

Only H20 Movement in Descending Limb


13/22


various segments of thevarious segments of the nephronnephron: TAL: TALGFR=180 L/day



V=1500 ml/day

UNa=67 mmol/L

.Urinary Na excretion 100 mmol/day

0.4% of filtered load 4grams


1Kg

1

33% remaining


371grams

2

8% remaining

NHE3Sodium Hydrogen

Exchanger

NKCC2Sodium Potassium

2Chloride Cotransporter

Sodium Absorption in Thick Ascending Loop

Bumetanide/

FurosemideXDiuretics (cause increased

urine flow) used to treat

high blood pressure


14/22


various segments of thevarious segments of the nephronnephron: TAL: TALGFR=180 L/day



V=..increase

UNa=increase

.

Urinary Na excretion load with diuretic???


1Kg

1

33% remaining


371grams

2

8% remaining?higher

NHE3

AQP1

AQP1

Glomerulus

Proximal tubule

Thin Descending

Limb of

Henles Loop

Thick

Ascending

Limb

Uses a lot of energy, dilutes urine


15/22


various segments of thevarious segments of the nephronnephron: DCT: DCTGFR=180 L/day




1Kg

1

33% remaining


371 grams

2

8% remaining


75grams

3

3% remaining

NaCl/TSC

Sodium ChlorideCotransporter/

Thiazide sensitive

cotransporter

Sodium Absorption in Distal Convoluted Tubule

Thiazides

X Diuretic used to treathigh blood pressure


16/22


various segments of thevarious segments of the nephronnephron: DCT: DCTGFR=180 L/day




1Kg

1

33% remaining


371 grams

2

8% remaining


75grams

3

3% remaining% remaining

increases

Urinary Na excretion increases with diuretic

NHE3

AQP1

AQP1

Glomerulus

Proximal tubule

Thin Descending

Limb of

Henles Loop

Thick

Ascending

Limb

Distal Convoluted

Tubule


17/22


various segments of thevarious segments of the nephronnephron: CD: CDGFR=180 L/day



700 mmol/day


18/22


various segments of thevarious segments of the nephronnephron: CD: CDGFR=180 L/day



700 mmol/day


19/22

Collecting Duct Water

Permeability is regulated

Vasopressin (VP)

AVP (Arginine Vasopressin)

Or also called

ADH Anti Diuretic Hormone

Pituitary

ADH

Osmoreceptors

Baroreceptor inputs

Vasopressin Secretion PathwayVasopressin Secretion Pathway

Urine is concentrated and flow reduced

Hypothalamus


20/22

NHE3 +AQP1

AQP1

Concentrating mechanism when vasopressin is low

Collecting Duct Water

Permeability is regulated

ADH Anti Diuretic Hormone

also called vasopressin

Activates the insertion of the water channel,

aquaporin-2, into the apical membrane of

the collecting duct


21/22

High vasopressin = Formation of concentrated urineHigh vasopressin = Formation of concentrated urine

NHE3 + AQP1NHE3 + AQP1

AQP1AQP1

AQP2AQP2

AA

QQ

PP

22

High vasopressin = Formation of concentrated urineHigh vasopressin = Formation of concentrated urine

NHE3 + AQP1NHE3 + AQP1

AQP1AQP1

AQP2AQP2

AA

QQ

PP

22


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Vasopressin signaling in collecting duct

VP

BLOOD LUMEN

AQP2V2

Gs

AC

VI

ATP

PKA

cAMP

H20

H20

AQP2

Nucleus?

AQP3/AQP4

Gene regulation?

renal lecture

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