Transcript kidney 7

‫بسم هللا الرحمن الرحيم‬
‫﴿و ما أوتيتم من العلم إال قليال﴾‬
‫صدق هللا العظيم‬
‫االسراء اية ‪58‬‬
By
Dr. Abdel Aziz M. Hussein
Lecturer of Medical Physiology
1. Glucose, amino acids,
vitamins, protein → 100%
2. HCO3- → 90%
3. inorganic phosphate → 80%
4. Na+ & water → 2/3 or 65%
5. K+, Ca2+, Mg2+ & urea →
Variable amount
Reabsorption
Organic solutes as PAH,
drugs, various amines and
ammonia.
Secretion
a) Reabsorption of:
1. All filtered glucose, amino acids, vitamins, protein
and Kreb’s cycle intermediates.
2. About 2/3 of filtered load of Na+ & water.
3. About 90% of the filtered load of HCO3- .
4. About 80% of the filtered inorganic phosphate.
5. Variable amount of K+, Ca2+, Mg2+ & urea.
b) Secretion of
• Organic solutes as PAH, drugs, various amines and
ammonia.
Descending LH:
Starts:
• At junction ( ) outer and inner strips of outer
medulla
Epithelium:
1. Very thin endothelial –like cells.
2. Few microvilli
3. Few mitochondria
4. Permeability (high to water, hard to solutes)
Outer
Strip
Inner
Strip
Ascending LH:
Thin ALH:
• Presents only in long loops
Epithelium:
1. Similar to DLH
2. Permeability
• Impermeable to water
• Permeable to solutes → allow Na reabsorption,
and Urea secretion
1120 = NaCl
80 = Urea
600 = NaCl
600 = Urea
Ascending LH:
Thick ALH:
Epithelium:
1.
2.
3.
4.
5.
Tall epithelium
Numerous microvilli
Much mitochondria
Basolateral border rich in Na-K pump
Apical border contain Na-K-Cl2 transporter
Apical
border
Basolateral
border
Tight
Junctions
Hypotonic fluid
TEPD
+ 5 to +15 mv
Na, Ca, Mg
+
+
+
150- 200 mosm/L
30% Ca
65% Mg
10 % K
25% Na
(6000-900
meq/day)
15% Water
Urea
• a) Distal convoluted tubule (early distal
tubules
• b) Connecting tubules (late distal tubule)
• c) Collecting ducts
DCT
CT
CD
1.
2.
3.
4.
5.
Final adjustment of urine formation.
Reabsorption of 7-10% of filtered load of Na+.
Reabsorption of 10-15% of filtered lead of water.
Secretion of variable amount of H+ & K+.
Major control site for Na+, K+, Ca2+ & acid-base
balance of body.
• Many of these functions are controlled by
hormones.
1. Represent early 2/3 of distal tubules.
2. Reabsorbs 4% of filtered load of Na+.
3. NaCl is transported by a Na+ - Cl- transporter located
at apical border.
4. This transporter is inhibited by thiazide diuretics.
5. The basolateral Na+- K+ ATPase together with that of
thick ALH has highest activity of any nephron
segment.
6. The osmolarity of tubular fluid leaving DCT is 100
mOsm/L (i.e. more hypotonic)  so, the diluting
segments of the nephron are: thick ALH and early
DCT.
• It is the late 1/3 of distal tubules.
• As the collecting duct, its cell types are principal
and intercalated cells.
• Has variable water permeability according to
ADH level.
• Its TEPD is negative (about -45 mV).
• Important site for final adjustment of urine volume,
reaction (pH) and composition.
• Include: cortical (CCD), outer medullary (MCD) & inner
medullary (papillary) (PCD).
• Have 2 major cell types:
• 1. Principal cells.
• 2. Intercalated cells.
CCD
MCD
PCD
Proximal segment
Distal segment
The main site of reabsorption of No reabsorption of nutritional
nutritional substances
substances
Reabsorption of large quantities Less absorption and smaller
of salt & water
capacity: 9% of filtered NaCl &
17%
Transport of salt and water occurs Steep gradient in early distal tubule
along small gradient so, fluid
and the fluid leaving collecting
leaving PT is isotonic.
duct is usually hypertonic.
Na+ concentration in urine is Na+ concentration in urine can be
about 140 meq/L as plasma.
as low as 1 meq/L.
Leaky tight junction.
Tight tight junction between the
epithelial cells causing the steep
gradient.
pH 6.9
pH as low as 4.6
Na+ reabsorption is coupled to Na+ and water reabsorption are
water.
uncoupled.
Not affected by aldosterone & Affected by Aldosterone & ADH.
ADH.
General characters
1. About 2/3 (67%) of the filtered Na+ with the same
percentage of water i.e. iso-osmotic reabsorp.
2. TFNa / PNa ratio at the end of PT is one as it is isoosmotic
3. In early PT, Na+, water, glucose, HCO3, amino
acids and organic anions as lactate, pyruvate, and
phosphate …. all are absorbed 2ry to Na+.
4. In the late PT: Na+ is absorbed with chloride
mainly.
Paracellular
Transport
Transcellular
Transport
•Occurs mostly at early segment of PT
a) Carrier –mediated transport
Symport
Na-K pump
Antiport
b) Channel –mediated transport
Na Channels
Na-K pump
Na-K pump
Electrogenic
symport
Electoneutral
symport
Na-K pump
Electoneutral
antiport
Cl ions
Na-K pump
Na channels
•Occurs mostly at late segment of PT
a) Cl- derived Na Reabsorp.
Early PT
HCO3Cl = 105 meq/L
Cl = 132 meq/L
Na+
-
Late PT
a) Solvent drag Reabsorp.
3-5
mosmol/L
PTC
Water
NaCl
• % : 100% of glucose is reabsorbed in PT
2ry active
transport
Na-K
ATPase
Facilitated
diffusion
• This process is saturable and rate limited, due to
saturation of the carrier, and it has a Tm.
• The excess filtered glucose is excreted in urine as
in DM.
• Also; phlorizin competes with glucose for this
transporter, thereby inhibiting glucose
reabsorption
• Galactose can compete with glucose at the luminal
border, so increase plasma glucose as in
pregnancy  glucose appears in urine
• Amino acids e.g. glutamate and glycine are
absorbed Na-dependent 2ry active transport
• The transport is limited due to saturation of the
carrier
• Proteins are reabsorbed after digestion by brush
border enzymes into amino acids or they may be
absorbed by endocytosis
• This process is easily saturated, so large
leakage of proteins in glomeruli → proteinuria
• They are absorbed by Na-dependent 2ry active
transport.
• There are 2 transport systems;
1. One for monocarboxylates as lactate, pyruvate.
2. Other for di-carboxylates as malate, succinate and
for tri-carboxylates as citrate.
• As PAH, oxalate, urate, creatinine and drugs as
penicillin and aspirin.
• Secretion occurs by a Tm-limited process using
transporters with low specificity (i.e. some
anions and cations compete with each others for
same transport system).
Primary
Secondary
Tertiary
• About 25% of the filtered load of Na+
• Is actively reabsorbed by a common transporter
for Na+ - k+ - 2Cl-.
• This transporter is inhibited by the loop diuretics
as frusemide and edecrine.
• This process plays a key role in counter current
multiplier system, responsible for medullary
gradient.
Hypotonic
CT and CDs reabsorb
about 8% of the filtered
load of Na+.
•
•
•
•
4% of filtered Na+
By common carrier with Cl-.
Is inhibited by thiazide diuretics.
Is impermeable to water, and the fluid leaving it is
more hypotonic
• So, thick ALH and early distal tubules are called
the diluting segments of the nephron.
• Types of cells;
1. Principle cell:
a. Reabsorbs Na+ via special channels.
• Is influenced by aldosterone (2% filtered Na )
b. Reabsorbs water (under control of ADH).
c. Secrete K+:
• K+ secretion is influenced by aldosterone hormone .
• Na+ is actively reabsorbed by the principal cell of the CT and
cortical CD mainly and to less extent by the outer MCD
• Na+ diffuses passively from tubular fluid into the cell via apical
epithelial Na+ channel (blocked by amiloride diuretics)
• It is actively pumped through the basolateral side, to the
interstitium by Na+ - K+ ATPase.
• K+ enters the cell by the basolateral Na+ - K+ ATPase
• High intracellular K+ → exits the cell via a basolateral K+
channel to the interstitium (recycling) or secreted via apical
K+ channels to tubular fluid.
• K+ secretion by these segments is the primary
determination of K+ secretion and excretion in urine;
therefore regulating K+ balance
• The absorption of Na+ across the apical border makes
the TEPD –ve up to -45 mv
• This help secretion of either K+ or H+ or reabsorption
of Cl- to paracellular space.
• Types of cells;
2. Intercalated cell :
a. Secretion of H+ by either;
• H+ ATPase
• K+- H+ ATPase
b. Reabsorb K+
Electrolyte
balance
Na
homeostasis
K
homeostasis
Water
balance
Regulation of
water output
pH
regulation
Reabsorption
of filtered
HCO3
Secretion of H
Distribution:
Intracellular
98%
concentration of 130
- 150 meq/L
Extracellular
2%
concentration of 130 150 meq/L.
1. Regulation of protein and glycogen
synthesis.
2. Control of cell volume
3. Regulation of intracellular pH
4. RMP & action potential of neurons
and muscles; thus affecting their
excitability
Input
Output
K intake
K excretion
by kidney
Shift between
ICF and ECF
Shift of K
between ICF
and ECF
• K+ is primary an intracellular cation
• 80% of the ingested K+ is moved temporary ICF to
prevent rapid elevation of ECF K+ concentration
which is dangerous
1. Na+ - K+ ATPase activity.
2. H+ ion concentration
3. Body fluid osmolarity.
4. Vitality of the cell membrane
a) Activators: insulin, β agonist, aldosterone, high K
• These factors increase K shift into ICF → hypokalaemia
b) Inhibitors: digitalis
• These factors decrease
K shift into ICF
→ hyperkalemia
1. Increase H+  exchange with intra cellular K+  K+
efflux  hyperkalemia
2. Decrease H+  opposite effect  hypokalemia
Decrease ECF osmolarity  shift of water ICF
together with K+  hypokalemia.
Increase ECF osmolarity  shift of water ECF
together with K+  hyperkalemia.
Exercise and cell lysis  K+ efflux  hyperkalemia
1. At the PT: about 80% of the filtered K+
2. At thick ALH: 10% of K+
3. Connecting tubule and cortical collecting ducts
where the actual K+ balance occurs:
• K+ is secreted by the principle cells in amount
ranging from 2% to 180% of the filtered K+.
• K+ secretion occurs 2ry to Na+ reabsorption→ help
increase of the electrochemical gradient for K+
secretion
• High gradient for K secretion is;
1. high K+ concentration inside the cell
2. –ve lumen (TEPD is – 45mvolt).
1. Plasma K+
• Increase K+ concentration  increase K+
secretion via:
a. Activation of Na+ - K+ ATPase  increase
intracellular K+
b. Stimulation of aldosterone hormones.
2. Tubular flow rate:
• Increase tubular flow rate  increase K+
secretion via:
a. Delivery of Na+ to the principle cell.
b. Dilution of the secreted K+
3) Acid - base status:
• Acidosis decrease K+ secretion.
• Alkalosis  increase K+ secretion.
4) Aldosterone :
• Aldosterone induced proteins (AIP)
• So, the delay of action of aldosterone for 1-2 hours
could be explained by the period necessary for the
synthesis of AIP
• The effectiveness of the kidney to control Na+
excretion is bitter than that for K+.
• For example, in complete Na+ deprivation, only
0.01% of the filtered Na+ is excreted in urine while in
complete deprivation of K+, 2% of the filtered K+ is
secreted and excreted in urine and so, hypokalemia
can develop.
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