Tubular Functions

Renal Physiology 2

Dr Raghuveer Choudhary

Q. List different functions of renal tubules - Reabsorption: Transport of substance from lumen of tubule to blood. - Secretion: addition of substance to the glomerular filtrate coming from blood . - Synthesis: addition of new substance to glomerular filtrate e.g ammonia.

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TUBULAR FUNCTIONThe glomerular filtrate is

formed at a rate of 125 ml/min. or 180 L/day. It passes to the renal tubules.

In the tubules, the tubular fluid is subjected to the 2 main tubular functions, reabsorption & secretion.

It is finally excreted as urine at a rate of about 1-2 ml/min. or ca. 1.5 L/day.

Reabsorption & Secretion Secretion:- refers to the transport of solutes

from pritubular capillaries in to the tubular lumen,i.e. it is the addition of substance to the filterate.

Reabsorption- denotes the active transport of solutes & passive movement of water from tubular lumen in to the peritubular capillaries,,i.e. the removal of a substance from the filterate

Filtered Load

Filtered load (mg/min) =GFR(ml/min) x Plasma Conc. of that solute(mg/ml)

Is the amount of solute transported across the glomerular membrane per unit time

Renal Tubular Transport Maximum (Tm)

Tm=it referes to maximum amount of a given solute that can be transported (reabsobed or secreted) per minutes by the renal tubules.

Tm – pertains to solutes that are actively transported.

Substances that are passively transported (urea) do not exhibit a Transport Maximum(Tm)

Tubular Reabsorption is a Function of the Epithelial Cells Making up the Tubule

Lumen

Plasma

Cells

substance to be reabsorbed must be transported

across the tubular epithelial membranes into the renal interstitial fluid

through the peritubular capillary membrane back into the blood

The transporting pathways of substance through the renal tubular

epithelial cells Transcellular pathway:

through the cell membranes

Paracellular pathway:

through the junctional spaces

Movement of substances in and out of cell

Types of carrier proteins – A uniport carrier: transport one substance. – A symport carrier: transport two substances in the same

direction. – An antiport carrier: transport two substances in the opposite

directions.

Mechanisms of Reabsorption

1. Passive transport

1). Down electrochemical gradient;

2). not require energy;

3). Mode:Diffusion,Osmosis,facilitated diffusion

4). Example:H2O

2. Active transport1). Against an electrochemical gradient;

2). require energy;

3). Depend on carrier proteins that penetrate through the membrane

4). divided into two types:– Primary active transport: coupled directly to an

energy source(hydrolysis of ATP)– Secondary active transport :coupled indirectly to

an energy source(an ion gradient)

Primary active transport is linked to hydrolysis of ATP

Importance: move solutes against an electrochemical gradient

energy source: hydrolysis of ATP Example: sodium-potassium ATPase pump

Inside Outside

Na+

Na+

Na+

K+

K+K+K+

Na+

Na+

Na+

Inside Outside

Na+ Na+Na+

K+

K+

K+

K+

Na+-K+ ATPase hydrolysis ATP release energy

Transport Na+ out of the cell into the interstitiumTransport K+ from the interstitium into the cell

The intracellular concentration of sodium is lower (chemical difference)The cell interior is electrically negative than the outside (electrical difference)

Favor Na+ to diffuse from the tubular lumen into the cell through the brush border

Secondary active transport

Co – transport:

glucose-sodium transport

amino acids -sodium transport

phosphate -sodium transport Counter- transport:

H+-Na+ transport

Co – transport ofGlucose (or amino Acids) along withSodium ions throughThe brush border ofThe tubular epithelialcells

Tubular Reabsorption

A) Active transport; against electrochemical gradient.(1) Primary active transport

Requires energy directly from ATP.Example; Na+ reabsorption in PCT

(2) Secondary active transport-It does not require energy direct from ATP.

a) Co-transport two substances bind to a specific carrier are cotransported in one direction.

b) Counter-transport two substances bind to a specific carrier are

transported in two directions.B) Passive reabsorption;

(1) Simple diffusionPassive reabsorption of chloride & Osmosis of water

(2) Facilitated diffusionNeed carrier.

C) PinocytosisIt is an active transport mechanism for reabsorption of proteins and

peptides in the proximal convoluted tubules.

Q. List different Characteristic features of PCT - PCT is about 15 mm long and 55 μm in diameter. - PCT wall is lined by single layer of epithelial cells that are connected by tight junctions at their luminal edges, but there is a space between the cells along the rest of their lateral borders (lateral intercellular spaces) which contains interstitial fluid. - The luminal borders of cells have brush border due to presence of large number of microvilli which increase surface area for reabsorption. - The PCT cells have large numbers of mitochondria (energy supply).

Proximal Convoluted Tubule

65% of the nephron function occurs in PCT.

The PCT has a single layer of cuboidal cells with millions of microvilli.

– Increased surface area for reabsorption.

PCT's main function is reabsorption.

The PCT is full of mitochondria

Reabsorption in Proximal Tubule

100% Glucose, protein and Amino Acids 60% Sodium, Cl, and H2O. 80% PH, HCO3, K. 60% Ca. 50% of Filtered Urea.

Reabsorption of glucose: Position: proximal tubule. All the filtrated glucose is reabsorbed under

normal condition. Secondary active transport, accompanied by

the primary active transport of sodium .

Renal threshold for glucose:

the maximal blood sugar concentration which can not result in glucosuria.

Reasons: there is a limit to the amount of transporter proteins and binding site.

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GLUCOSE:

At normal blood glucose levels (~100 mg%), glucose is freely filtered at a rate of 125 mg/min. (= plasma conc. X GFR = 100 mg% x 125 ml/min.). The amount filtered is completely reabsorbed from the upper half of PCT by Na+-glucose cotransport (mechanism: see before).

There is, however, a limited number of Na+-glucose carriers:a- At a blood glucose level of less than 180 mg%, all the filtered glucose can be reabsorbed because plenty of carriers are available. b- At a blood glucose level of 180 mg%, glucose starts to appear in urine. This level of blood glucose is called the renal threshold for glucose. It corresponds to a renal tubular load of 220 mg/min.

c- At a renal tubular load of glucose of 320 mg/min, all the carriers are saturated, i.e., the transport maximum for glucose, TmG, is reached.

Any further in filtered glucose is not reabsorbed & is excreted in urine.

Glucose reabsorption The transporter for glucose on the basolateral

membrane has a limited capacity to carry glucose back into the blood. If blood glucose rises above 180 mg/dl, some of the glucose fails to be reabsorbed and remains in the urine glucosuria.

Tubular maximum for glucose (TmG):

The maximum amount of glucose (in mg ) that can be reabsorbed per min.

It equals the sum of TmG of all nephrons. Value; 300 mg/min in ♀ , 375 mg/ min in ♂.

Renal Threshold for Glucose • Is approximately 180 mg/dl• If plasma glucose is greater than 180 mg/dl:

– Tm of tubular cells is exceeded

– glucose appears in urine

Plasma Glucose (mg%)

Glucose filtered (mg/min)PG x GFR/100

100 125

200 250

300 375

400 500

500 625

600 750

180

180

180

GLUCOSE REABSORPTION HAS A TUBULAR MAXIMUM

Plasma Concentration of Glucose

GlucoseReabsorbedmg/min

Filtered Excreted

Reabsorbed

375mg/min

Glucose titration curve

Plasma Glucose (mg%)

Glucose filtered (mg/min)PG x GFR/100

100 125200 250300 375400 500500 625600 750

180

Glucosuriapresence of glucose in urine

1. Diabetes mellitus –blood glucose level > renal threshold.

2. Renal glucosuria –It is caused by the defect in the glucose transport mechanism.

3. Phlorhizin–A plant glucoside which competes with glucose for the carrier and results in glucosuria (phloridzin diabetes).

Glucose

filtration rate = 100 mg/min (Pc x GFR) reabsorption rate = 100 mg/min

– site = early portion of the proximal tubule secretion rate = 0 mg/min excretion rate = 0 mg / min Tm = 375 mg/min ideal renal threshold = 300 mg/dL actual renal threshold = 200 mg /dL (arterial) 180 mg/dL (venous)

– “splay”

SGLT 2

PHLORHIZIN

GLUCOSE

100 % REABSORBED

Amino Acids

filtration rate --- small amount reabsorption ---- 100 %

– site -- early portion of the proximal tubule secretion ---- 0 excretion ----- 0

amino acids

amino acids

amino acids

SIMPLE OR FACILITATED DIFFUSION

AMINO ACIDS

100 % REABSORBED

Proteins

peptide hormones, small proteins and small amount of albumin

filtration rate = 7.2 g/day (GFR x protein in the ultrafiltrate)

reabsorption rate = 7.2 g/day– site --- early portion of the proximal tubule

secretion rate = 0 excretion rate = 0

PROTEINS

Endocytosis of Proteins

mediated by apical membrane proteins that specifically bind with luminal proteins and peptides.

they are multiligand endocytic receptors.– Megalin– Cubilin

PROTEINS

100 % REABSORBED

Sodium

filtration rate = 25,560 mEq/day (575-580mg/day)

reabsorption rate = 25,410 mEq/day (98%)– site -- proximal tubule, loop of Henle, distal

tubules and collecting duct. secretion rate = 0 mEq/day excretion rate = 150 mEq/ day

67%

Sodium 25%

5%

1 %

3%

Na reabsorption At basolateral side of the tubular epithelial cell there is an

extensive Na+-K+ ATPase system (= Na+-K+ pump).It pumps 3 Na+ actively out of the cell into the interstitium, and

at the same time carries 2 K+ into the cell.But K+ will diffuse immediately back into the interstitium due

to:(1) high concentration gradient & (2) high permeability of epithelial cells to K+.

As a result of this there is:- intracellular Na+ concentration

At luminal membrane there will therefore be passive diffusion of Na+ into the cell along concentration gradient created by the Na+-K+ pump. This diffusion is facilitated by a protein carrier.

In the early distaltubule, NaCl reabsorption is coupled via a Na-Cl cotransporter. Na+ exit at the basolateral membrane is via the Na/K-ATPase, and Cl− exit is via the Cl− channel.

Late DCT & Cortical CD:(1) Principal Cells:

a. They actively reabsorb Na+ in exchange for K+ secretion. This action is increased by aldosterone.b. Antidiuretic hormone (ADH) causes reabsorption of H2O. In the absence of ADH, the principal cells are impermeable to H2O.

(2) -Intercalated Cells: - These cells secrete H+ .This action is

increased by aldosterone.

DISTAL TUBULE AND CORTICAL COLLECTING DUCT

The distal tubule and the cortical collecting duct are important areas for fi ne regulation of Na+ excretion. The hormone aldosteroneincreases the activity of the Na+ transport proteinsthroughout this area to promote renal Na+ conservation and maintain the extracellular fl uid volume.

DIURETICSDiuresis is defined as an increase in the urine flow rate; diuretics = agents that induce diuresis.

Regulation of sodium excretion

Glomerulotubular balance in PT

Effect of ECF volume on PT Reabsorption

ECFV contraction-increased absorption ECFV expansion-decreased absorption

Factors affecting Na reabsoptionNa reabsorption increased by Na reabsorption decreased by

Peritubular Hydrostatic pressure Peritubular Hydrostatic pressure

Peritubular Colloidal osmotic pressure

Peritubular Colloidal osmotic pressure

ECFV contraction ECFV expansion

Aldosterone Glucocorticoids

GFR decreased GFR

95

Hormones acting on the kidney1. Aldosterone: Stimulus for its secretion:

Blood volume (via renin-angiotentin system). Actions & their site:

It stimulates Na+ reabsorption in DCT & cortical CD through:

1) In principal cells: Na+ reabsorption in exchange with K+.

2) In -intercalated cells: Na+ reabsorption in exchange with H+.2. Angiotensin II: It is the most powerful Na+ retaining hormone. Stimulus for its secretion: arterial bl. pressure & blood volume, e.g., hemorrhage (via renin). Actions & their site: 1. It Na+ reabsorption by several mechanisms: a. By stimulating aldosterone secretion. b. In PCT: - By directly stimulating Na+-K+ ATPase at basolateral border.

- By directly stimulating Na+-H+ countertransp. at luminal border.

2. It constricts efferent arterioles.

Hormones affecting Na Reabsorption

Nacl & water reabsorption by Aldosteron,Angiotensin II

water reabsorption- Antidiuretic Hormone ADH

Nacl & water reabsorption- ANP,Dopamine,Urodilatin

Hormones that influence sodium reabsorption in renal tubules

Angiotensin II– stimulates sodium reabsorption in the

proximal tubule, thick ascending limb, distal tubule and collecting duct.

Aldosterone– increases sodium reabsorption and

potassium secretion in the distal tubule and collecting duct

– increases sodium reabsorption in the thick ascending limb

Hormones that influence sodium reabsorption in renal tubules

Atrial Natriuretic Peptide and Brain Natriuretic Peptide– inhibits sodium chloride reabsorption in the

medullary collecting duct– inhibits ADH secretion in the posterior

pituitary gland Catecholamines

– stimulates sodium chloride reabsorption in the PT, thick ascending, DT and CD

Hormones that influence sodium reabsorption in renal tubules

Dopamine– inhibits reabsorption of sodium chloride in

the proximal tubule Adrenomedullin, Urodilatin, Uroguanylin

and guanylin– increases sodium chloride excretion

Potassium

ECF K+ concentration (N = 3.5 - 5.5 meq/L) ICF - 98%, ECF - 2% excretion

– kidneys - 90 - 95%– feces - 5 - 10%

ICF K+ concentration

140 mEq/L X 28 L

3920 mEq

ECF K+ concentration

4.2 mEq/L X 14 L

59 mEq

K+ intake100 mEq/day

K+ outputUrine = 92 mEq/dayFeces = 8 mEq/day

NORMAL K+ INTAKE, DISTRIBUTION OF K+ IN THE BODY FLUIDS AND OUTPUT FROM THE BODYGuyton, Medical Physiology, 2006

filtration rate = 756 mEq/day reabsorption rate = 644 mEq/day (87.8%)

– site -- proximal tubule and ascendong loop of Henle

secretion rate = 31 mEq/day excretion rate = 92 mEq/ day

67%

POTASSIUM20 -25%

4%

12%

Increased ECF potassium concentrationIncreased aldosteroneIncreased tubular flow rate

K+ and acid base disorders

Bicarbonate Reabsorption

Recovery of filtered HCO3− and net acid excretion is usually required to maintain acid-base balance—almost all the filtered HCO3− must be recovered. Most HCO3− reabsorption occurs in the early proximal tubule via the mechanism shown in Figure

Mechanisms of H+ excretion and HCO3− generation.B. Titratable acid excretion as H2PO4 − occurs when secreted H+ combines with fi ltered HPO42−. CA, carbonic anhydrase.

Mechanisms of H+ excretion and HCO3− generation.A. Renal ammoniagenesis results in the formation of NH4+ within cells because NH3 readily combines with H+ at physiologic pH. NH4 +is secreted via the Na/H exchangers

Reabsorption of water: 1. Quantity of reasorption:99% 2. Passive reabsorption: osmotic pressure 3. Position and siginificance: Proximal tubule: 65-70%; Accompanied by the reabsorption of NaCl Has nothing to do with whether the body lack

water or not. Not regulated by hormones;

THANK YOU