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RENAL MODULE
SOLA AOUN BAHOUS
Functions of Distal Segmentsof the Renal Tubule
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Outline
Cell types of the renal tubule
Permeability of tubular segments to water and
solutes Effect of hormones on distal segments
Review of processes of peri-tubular capillary uptakeof solutes
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Outline
Cell types of the renal tubule
Permeability of tubular segments to water and
solutes Effect of hormones on distal segments
Review of processes of peri-tubular capillary uptakeof solutes
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Cell Types of the Renal Tubule
Before the distal convoluted tubule: cells in anysegment are homogeneous and distinct for that
segment
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Cell Types of the Renal Tubule
Beginning in the 2nd half of the DCT, two cell typesare found:
> one type constitutes the majority of cellsin the particular segment: DCT cells, connectingtubule cells… = principal cells
> interspersed cells = intercalated cells
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Outline
Cell types of the renal tubule
Permeability of tubular segments to water
and solutes Effect of hormones on distal segments
Review of processes of peri-tubular capillary uptakeof solutes
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Permeability of Tubular Epithelium
Proximal tubules have leaky epithelia i.e.permeable tight junctions: they have high waterpermeability and low TTP
Distal convoluted tubules and collecting ducts havetight epithelia i.e. less permeable tight junctions:
they have low water permeability and high TTPdistal if asked is considered impermeable ,, bas l collecting is called relative permeability
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Permeability of Tubular Epithelium
Beyond Henle’s loop: fine tuning for mostsubstances. They determine the final amounts
excreted in urine by adjusting their rate ofreabsorption and, in a few cases, secretion. Majorsite for homeostatic control
what determines the final amount that will appear in urine is the function of the collecting
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Permeability of Tubular Epithelium
The segments of the renal tubule fall into 3categories with regard to permeability to water:
* proximal tubule and descending thin
limb have very high permeability to water
* ascending limbs and DCT are relativelyimpermeable to water
* collecting duct system has a regulated water permeability (ADH-dependent)
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Permeability of Tubular Epithelium
DCT and collecting duct system:
second half of the distal
we have overlap btwn segmentsbas iza Nacl only then pure distalwhen Na 2 cl then loop of henlebas iza Nacl w another one like hereso second half of distal
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Permeability of Tubular Epithelium
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Permeability of Tubular Epithelium
Type A intercalated cell – Adapted from www.ikcl.uniklinikum-jena.de/Research-page-10...14
only type of cell with na/k atpase pump on basolateral
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Permeability of Tubular Epithelium
Type-B intercalated cells are present only in the CCD
Type-B intercalated cell is a “flipped-around” type-Aintercalated cell
Involved mainly in bicarbonate secretiontype B secretes bicarbonate
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Permeability of Tubular Epithelium
In Summary:
DCT is almost impermeable to water fluidentering the collecting duct is even morehypoosmotic than that entering the DCT DCT isalso a diluting segment
Water permeability of the collecting duct is subject tophysiological control by the hormone vasopressin or ADH
ma khas the part that absorbs water ,, ma byirja3 bya3mila ..so it will hypososmotic bas never hyperosmotic compared toplasma
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Permeability of Tubular Epithelium
Under low ADH levels, solutes reabsorption butnot water continues to occur in the collecting ductand the final urine is dilute or hypoosmotic (waterdiuresis)
Under high ADH levels, water permeability of the
collecting duct is high
water will move followingosmotic gradients: the cortical collecting ductbehaves like the proximal tubule ya3ne isomosmotic ya3ne removes all effect of
loop of henle btirja3 300 osmolarity ,, itreabsorbs the volume salt and water andmakes concentrated medulla
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Permeability of Tubular Epithelium
Interstitial fluid in the cortex has an osmolarity ~ tothat of plasma when collecting duct is permeable to water, it undoes the dilution carried out by the diluting
segment
In the medullary collecting duct water reabsorption iseven higher (in the presence of ADH) because the
interstitial fluid is hyperosmotic in the medulla thefinal urine is hyperosmotic
antime we have ADH on board will absorb water in cortical collecting duct la seer 300 w bil medulla bitseer 1400 bcz medullaconcentrated w which made it hek is loop of henle w urea recycling there w Cl-
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Permeability of Tubular Epithelium
The tubular response to ADH is not all or none
ADH acts on principal cells via V2 receptors
always have ADH
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Permeability of Tubular Epithelium
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Permeability of Tubular Epithelium
thats why fluid hypotonic
bas major water permeability is regulated byADH
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Outline
Cell types of the renal tubule
Permeability of tubular segments to water and
solutes Effect of hormones on distal segments
Review of processes of peri-tubular capillary uptakeof solutes
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Effect of Hormones on Distal Segments
Aldosterone:
Hormone produced by the zona glomerulosa of the
adrenal cortex Acts mainly on the principal cells of the collecting
duct for fine-tuning of Na+ excretion: it stimulates Na+
reabsorption
Acts also on other epithelia/ intestinal epithelium,sweat glands, and salivary ducts (Na+ retention)
binds to its receptor mineralocorticoid w mish bas kidney it has receptors in GI
aldostersone will be responsible will be for the 4-5 hasab l table li able ,, so we ask ino kif fine tuning w hine 4-5 bas so bilcoming slides
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Effect of Hormones on Distal Segments
Aldosterone is responsible of the regulation of theexcretion of 2% of the filtered Na+
Total filtered Na+/day = GFRxPNa = 180 L/d x 145mmol/L = 26,100 mmol/day
2% of 26,100 mmol/day = 522 mmol Na+/day ~ 30 gNaCl / day: considerably more than the average personeats
plasma conc of sodium
the 2% of filtered load is more than what the person can eat
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Effect of Hormones on Distal Segments
Therefore, by reflex variation of the plasmaconcentration of aldosterone between minimal and
maximal, the excretion of Na+
can be adjusted to theintake so that total-body sodium and EC volumeremain constant
GFR is a constant parameter .. what will change is adjust hemeo is absorption
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Effect of Hormones on Distal Segments
aldosteroen comes and binds tomineralo receptors then goes tonucleus a w bisir fi proteins makingso by binding of aldo we increasenumber of channels available for rebasortionof sodium
primary hyperaldo: hypertension , hypokalemia
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Effect of Hormones on Distal Segments
Aldosterone binds to intracellular receptors: thecomplex MR-A moves to the nucleus and binds tospecific DNA sequences, stimulating the synthesis ofmRNA which mediates translation of specific proteins
The effects of these proteins are to increase the activity
and/or the number of luminal Na+
channels and basolateral Na-K-ATPase pumps
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Effect of Hormones on Distal Segments
primary hyperaldo is associated with metabolic alkalosis bcz increase [] of hydrogen ion .. kamen fi hypertension whypokalemia as said before
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Effect of Hormones on Distal Segments
Control of aldosterone secretion:
ACTH controls Aldo secretion to some extent but the
secretion of ACTH is not keyed to Na+
homeostasis
The most important stimulator of Aldo secretion is Angiotensin II
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Effect of Hormones on Distal Segments
Atrial natriuretic peptide (ANP)
• Secreted by cells of cardiac atria in response todistension
• Acts directly on the collecting duct system to inhibit Nareabsorption (mainly through inhibition of luminal Nachannels)
• Acts directly on granular cells to decrease reninsecretion
fi autoregulation myogenic w tubular feedback w houl occur in seconds after change bas kamenkidneys mish bas maintain internal environment it will sense the systemic changes w react to them wthis will have cross talk bil juxta w renin angiotensin which will take time to act bas kamen at level of
absorption mish level of GFR
distension is an increase in volume so iza patient ija w 3tayne volume kteer so this volume mish bas sensed bil baroreceptorsw bil renal ones,, fi kamen bil atrium of heart and releases ANP ,, lama y2el l renin, w it lowers sodium reabosprion ,, so wehave ANP so they potentiate each other by affecting reabsoprtion
principal cells
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Effect of Hormones on Distal Segments
Atrial natriuretic peptide (ANP)
Acts directly on the adrenal cortex: inhibits Ang II-induced aldosterone secretion
Increases GFR by acting directly on arterioles(afferent dilation and efferent constriction) this is not sth that
perpetuates
GFR is like cardiac output tightly regulated so hata law l ANP 3emlet those stuff ha yirja3 l myogenic reflex that senses l GFRbas l effect on tubules remains
ADH is regulated by osmolarity w volume bas it is more sensitive lal osmolarity bas mish more powerful,, l volume is more
powerful ,, l volume iza fi shway change ma ha ya3mol shi ADH so sensitive more lal osmolarity bas iza l volume so huge ADHcares for that 3a 7seb l osmolarity
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Outline
Cell types of the renal tubule
Permeability of tubular segments to water and
solutes Effect of hormones on distal segments
Review of processes of peri-tubular capillaryuptake of solutes
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Peritubular Capillary Uptake
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Peritubular Capillary Uptake
Fluid uptake by peritubular capillaries:
Major mechanism = net balance of hydrostatic and
oncotic pressures
Diffusion occurs for some substances/ glucose
Same type of dynamics that occur across all capillariesin the body
some substances diffuse w dont need transporters like glucose bas yseer interstituim ma bado pressure di8re birou7 peritubularcapillaries
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Peritubular Capillary Uptake
Fluid uptake by peritubular capillaries:
Pnet = PInt + PC – Int – PPC
The net filtration pressure across the peritubularcapillaries always favors net movement into thecapillaries
is always toward rebasorption bcz of efferent arteriole which drops hydorstatic pressure
w kamen fi increase in oncotic in glomerulus near efferent arteriole end + efferent will drophydrostatic pressure
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Peritubular Capillary Uptake
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