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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.
TUBULAR FUNCTION
The
glomerular filtrate is formed at a rate of 125 ml/min. or 180 L/day. It passes to the renal tubules. the tubules, the tubular fluid is subjected to the 2 main tubular functions, reabsorption & secretion. is finally excreted as urine at a rate of about 1-2 ml/min. or ca. 1.5 L/day.
In
It
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
Plasma
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
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 transport
1). 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)
Inside
Na+
Outside
Na+
Na+ K+ K+
Inside
Outside
K+
K+
Na+-K+ ATPase hydrolysis ATP release energy Transport Na+ out of the cell into the interstitium Transport 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
Co transport of Glucose (or amino Acids) along with Sodium ions through The brush border of The tubular epithelial cells
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.
C) Pinocytosis
It 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 m 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).
of the nephron function occurs in PCT. The PCT has a single layer of cuboidal cells with millions of microvilli.
Increased surface reabsorption.
PCT's
area
for
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 .
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.
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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.
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 .
Glucose filtered (mg/min) PG x GFR/100 125 250 375 500 625 750
180
180
180
Filtered
Excreted
Reabsorbed
375mg/min
Glucose filtered (mg/min) PG x GFR/100 125 250 375 500 625 750
180
Glucosuria
presence 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
PHLORHIZIN
SGLT 2
100 % REABSORBED
GLUCOSE
Amino Acids
filtration rate --- small amount reabsorption ---- 100 %
amino acids
SIMPLE OR FACILITATED DIFFUSION
100 % REABSORBED
AMINO ACIDS
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
PROTEINS
Endocytosis of Proteins
mediated by apical membrane proteins that specifically bind with luminal proteins and peptides. they are multiligand endocytic receptors.
Megalin Cubilin
100 % REABSORBED
PROTEINS
Sodium
filtration rate = 25,560 mEq/day (575580mg/day) reabsorption rate = 25,410 mEq/day (98%)
site -- proximal tubule, loop of Henle, distal tubules and collecting duct.
67% 5%
Sodium 25%
3%
1%
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 distal tubule, NaCl reabsorption is coupled via a NaCl 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.
The distal tubule and the cortical collecting duct are important areas for fi ne regulation of Na+ excretion. The hormone aldosterone increases the activity of the Na+ transport proteins throughout this area to promote renal Na+ conservation and maintain the extracellular fl uid volume.
DIURETICS Diuresis is defined as an increase in the urine flow rate; diuretics = agents that induce diuresis.
Aldosterone
GFR
Glucocorticoids
decreased GFR
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+.
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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
Catecholamines
stimulates sodium chloride reabsorption in the PT, thick ascending, DT and CD
Dopamine
inhibits reabsorption of sodium chloride in the proximal tubule
Potassium
ECF K+ concentration (N = 3.5 - 5.5 meq/L) ICF - 98%, ECF - 2% excretion
ECF K+ concentration
ICF K+ concentration
140 mEq/L X 28 L
3920 mEq
NORMAL K+ INTAKE, DISTRIBUTION OF K+ IN THE BODY FLUIDS AND OUTPUT FROM THE BODY Guyton, Medical Physiology, 2006
67% 4%
POTASSIUM 20 -25%
Increased ECF potassium concentration Increased aldosterone Increased tubular flow rate
12%
Bicarbonate Reabsorption
Recovery of filtered HCO3 and net acid excretion is usually required to maintain acid-base balancealmost 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;
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