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Physiology: Renal Tubular Processing - Dr. Najeeb

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Urine excretion involves
Glomerular filtration-
Tubular reabsorption+
Tubular secretion= urine excretion
What are the main solutes reabsorbed thru the proximal convoluted tubule?
65% Sodium, Chloride, H20
100% Glucose and amino acids
How does sodium and potassium move through the baso-lateral membrane from the proximal convoluted tubule?
Na-K-ATPase active transport system against the high gradient - 3 Na exchange for 2 K
Movement of Na from filtration:
Filtration through glomerulus into lumen, facilitated diffusion by sodium carrier proteins in lumen membrane->Na-K-ATPase active transport system to interstitial fluid -> paratubular capillaries
Sodium transporter protein carries
sodium - facilitated diffusion, glucose - secondary active transport because it is against the gradient
If the Na-K-ATPase active transport system is damaged what occurs to sodium and glucose?
diffusion and transport are restricted so sodium and glucose do not enter the cell
What transports amino acids?
sodium/aa transporter - binds sodium on one side and aa on the other - sodium facilitated diffusion because it is with the gradient and aa by secondary active transport because it is against the gradient
where are Na-K-ATPase active transport systems located?
baso-lateral membrane
Where are sodium/glucose transporters and sodium/aa transporters located?
lumen membrane
How does glucose diffuse out of cell and where?
diffuses through basolateral side glucose channels by facilitated diffusion - lets glucose diffuse out into interstitial fluid blood
How does chloride diffuse out of cell and where?
sodium/CL transporter late in the proximal tubule- binds sodium on one receptor and CL on the other - sodium facilitated diffusion because it is with the gradient and sodium/aa transporter - binds sodium on one side and aa on the other - sodium facilitated diffusion because it is with the gradient and aa by secondary active transport because it is against the gradient by secondary active transport because it is against the gradient
How do remaining solutes get reabsorbed?
solvent drag - Because a lot of solutes have moved to the interstitial H20 will follow. So remaining solutes in lumen are passively diffused along with H20 from luminal side thru paracellular route to the interstitial.
How does chloride move?
1. with sodium transporter (further down the proximal tubule)
2. with solvent drag
Active transport of solutes moves against
concentration and electrochemical gradient
What proteins are filtered and actively transported through the proximal lumen to the cells?
low molecular weight proteins - Insulin and free hemoglobin
What happens to insulin?
It is catabolised in to amino acids and released into blood. Uses carbon skeleton to synthesize new glucose
How are proteins filtered into cell?
pinocytosis
What are the three forms of active transport through the proximal tubule?
Primary active
Secondary active
pinocytosis
What are the 4 transporters in the proximal convoluted tubule through which sodium is moved into the cell and reabsorbed?
cotransporter - by facilitated diffusion and secondary active transport with glucose, aa, chloride and by counter transporter facilitated diffusion and with H+ on the cell side. and sovlent drag
Sodium movement into cell depends on
sodium concentration in lumen and cell
sodium electro-chemical gradient
renal tubular flow time - if fast, less can move thru
What hormone increases the synthesis of Na-K ATPase on the baso-lateral membrane and what does this cause?
Aldosterone - causes an increase of sodium transport and potassium import along with increased sodium reabsorption from the tubule into the cell
The proton (H+) will bind with
Bicarb (HCO3) and bind to produce carbonic acid H2CO3 which will disassociate into H20 and CO2. CO2 will diffuse into cell and combine with H2O and form H2CO3 which will dissociate into HCO3 and H+. HCO3 will be provided to the blood and H+ used to bring in more sodium
Glucose, amino acids, chloride, and bicarb leave the cell by
facilitated diffusion channels
What causes the pull of water from the tubule into the interstitial?
The high osmotic pressure outside the cell due to the high concentration of diffused solutes
What substances are secreted from the interstitial into the proximal tubule?
oxalates, bile salts, ureates, catecholamines (norepiniphrine, epinephrine, dopamine), toxins/drugs
What hormones work in the proximal tubule? And distal tubule?
PTH - blocks PO4 (phosphate), activates alpha-1 hydroxylase for Vit D. in distal it reabsorbs calcium
What is the osmolarity of the body fluids? Of plasma and of filtrate?
all 300 mOsm/L
When fluid is leaving proximal into loop what is its osmolarity?
300
What are the changes of the interstitial fluid and Loop of Henle as you move deeper into the medulla?
it increases in osmolarity - becomes hyperosmotic - due to increased amt of solutes. an additional 20% of water from the descending loop of henle and allows solutes to enter
What is the osmolarity of the interstitial and the loop of henley?
1200
What area of the tubs is impermeable to water?
thin ascending loop and thick ascending loop and early part of distal
What transporter lies on the lumen of the thick ascending loop?
Na-K-2chloride cotransporter
What drugs work to inhibit the sodium-potassium-2chloride cotransporter?
loop diuretics
When the sodium-potassium-2chloride cotransporter brings these ions into the thick ascending loop cells what happens to them?
sodium goes out via Na-K ATPase pump, Chloride goes out through channels. Sodium is at high concentration so it goes out through channels on basolateral membrane side and on lumen side
What is potassiums role on the ascending loop of henle?
It keep the lumen potential positive. So it repels positive Ca++ and Mg++ out of the cell paracellularly
At the distal tubule what is the osmolarity?
Hypo-osmolar - 100 mOsm/L
How do loop diuretics work?
they block Na, Cl, and K, produce naturesis and diuresis, pulling water along the tube and out. They also reduce the electropositivity of the lumen due to K blocking, causing Ca and Mg to be excreted. = loss of sodium, K, Cl, Ca and Mg
The thick ascending loop of henle is responsible for
concentrating solutes in the interstitiumand make it hyperosmolar; also diluting the fluid in the lumen making it hypo-osmolar
The early distal tubule
is water impermeable
throws solutes out making it further diluted
has macula densa cells
Macula densa
cells at distal tubule. Monitor filtrate osmolarity. If a drop is sensed, the macula densa dilates the afferent arteriole (to increase pressure in the glomerulus to increase filtration) and stimulates renin secretion to raise systemic BP.
The early distal tubule cells
have Na K ATPase, Na-Cl cotransporter, Ca-ATPase transporter, Ca-Na exchanger,
What blocks the distal tubule Na-Cl cotransporter and what does it cause?
thiazide. results in reduced Na and Cl reabsorption, causing naturesis, and will also pull water along with it and cause diuresis
Naturesis
Secretion of excess sodium in the urine
Diuresis
increased formation and secretion of urine
How does Ca go into and out of the distal tubule?
Ca channels on the lumen side
Ca-ATPase transporter, Ca-Na exchanger,
What hormone causes Ca to pass into and out of the distal tubule?
PTH
What does thiazide do?
hypo-calci-uric drug. It blocks the sodium transporter so sodium is decreased in the cell. So the Ca-Na exchange increases in activity - Na will come in from the interstitial and Ca will go into interstitial to be reabsorbed, decreasing the urinary Ca loss.
What patients with hypercalcemia who produce recurrent renal stones?
Those with hypercalciurea - give thiazide.
Late distal and cortical collecting tubule have two cells
intercalated and principal cells
Intercalated cells are
-in late distal and cortical collecting tubule
-are intercalated between principal cells
-are acid/proton secreting cells
-have active transporter H+ ATPase on the lumenal side
-have HCO3 channels on basolateral membrane to provide HCO3 for interstitial fluid
active transporter H+ ATPase
secreted H+ into lumen and
What binds with the H+ in the late distal tubule when it is transported into the lumen?
HPO3 + H+=H2PO4
NH3 (ammonium) + H+ = NH4 and binds with Cl to make NH4Cl which cannot be reabsorbed
When body develops acidosis what enzyme is stimulated?
carbonic anhydrase
What other bicarb is produced in the interstitium?
potassium bicarb, when K goes thru channel to interstitial and binds with HC03=KHCO3
What drug causes naturesis and diuresis?
loop diuretics
Function of the intercalated cells are
active secretion of protons on lumen and provide bicarb to the blood and with Ca
Principal cells in late distal and cortical collecting tubule have what transporters and receptors?
Na-K ATPase, Na & K channels on lumen membrane. The Na channels take Na into the cell and the K channels take K from the cell into the lumen - excess K in cell from Na-K ATPase
Receptors for aldosterone
Potassium comes from where when it moves into the cell via the Na-K ATPase pump in Principal cells?
the blood
What enhances the function of the principal cells?
Aldosterone, released by the glomerosa of the renal cortex. With aldosterone complex - translocate to nucleus and increase the expression of genes to produce more Na-K ATPase, Na and K channels on basolateral membrane
In diseases where aldosterone level is high in the blood
excessive Na and water retention and excess K lost in urine
Sodium is excreted in what percentages and where:
65% in proximal
25% in thick ascending loop
5-7% in distal
3-7% in collecting
hypocalemia
low level of potassium in blood- can be caused by diuretics working proximal to the principal cells, because they cause excess loss of potassium into urine from principal cells,
What diuretic drug blocks aldosterone and has a potassium sparing effect?
Spironolactone. Potassium sparing diuretic.
Blocks gene activation of channels and Ca-K-ATPase. Less Na will enter into cell, Less K will leave cell to lumen, Less Na will go to blood and less K will be taken from blood into cell. Less K will be lost. Salt and water will not be retained. More Na and water in urine
What potassium sparing diuretic drugs block Na channels on the lumen side of the principal cells and what is the effect?
Triamterin and Amiloride
1-decrease Na in cell - more Na in lumen and water follows to be excreted - so mild naturesis and diuresis.
2-Na-K ATPase slows-> less K in cell, so less K moves into lumen and less in urine
AP2, AP3 and AP4 are
water channels
What parts of the tubule is highly permeable to urea?
Only the medullary collecting tubule. So the rest of the tubule has high urea. This part of the tubule has urea channels. Some goes thru to medullary interstitial and some thru urine.
What is urea recycling?
urea is reabsorbed and carried to loop of Henley and back into lumn
ADH
at 32 minutes
Erythropoietin cells are produced by
epithelial cells of the peritubular capillaries
Vitamin D is activated in the
proximal convoluted tubules
Renin is produced by
juxtaglomerular apparatus
Vasa Recta
are in juxtaglomerulus
podocytes
are visceral epithelial cells connected to parietal epithelial cells - forms the bowmans capsule
mesengial cells
form the mesengium - can contract, phagocytoze,
What lines the glomerular capillaries
fenestrated endothelial cells - allows filtrates through