P1251955652ZGijB

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Evolution of the Vertebrate Kidney
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Fish Nephrons - typically have a glomerulus -
Bowmans capsule with a ciliated neck region that
connects to the rest of the tubule - cilia may
assist flow through tubule, since fish
typically have low filtration pressures -
neck region usually present in amphibians, but
not in amniotes
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Elasmobranches nephrons - urine is about
iso-ionic with the plasma with respect to Na
and Cl - hyperionic for Mg and SO4 - slightly
hyperosmotic to plasma - actively reabsorbs many
solutes particularly urea and TMAO dogfish
Squalus - reabsorbs 90-95 of filtered urea -
reabsorbs 95-98 of filtered TMAO - urea
retention involves countercurrent exchange in
the kidney that is linked to Na reabsorption
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Amphibians - have two types of nephrons -
collects coelomic fluid (coelomstome) -
glomerulus directly interacts with nephron -
generally function like freshwater teleost
nephrons - produce copious amounts of dilute
urine - high glomerular filtration rates ( 25
100 ml/kg/hr) - high urine flow ( 10-25
ml/kg/hr) - ½ of the primary filtrate is
reabsorbed - about 99 of the filtered ions are
reabsorbed - GFR and tubular reabsorptive
processes can be regulated in response to
dilution/ dehydration - dehydration causes
release of arginine vasotocin - hormone that has
both glomerular and tubular reabsorptive effects
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Reptiles and birds   - generally adapted to
minimize urinary water loss and excrete solutes (
nitrogenous wastes and ions)
Birds and Mammals   - can produce a very
hyperosmotic urine
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The mammalian kidney    humans - small about 1
of body mass - receive about 20-25 of the
cardiac output - produce about a liter of per
urine per day - composition and volume reflects
volume of liquid and types of food ingested -
function- maintain a more or less constant body
composition
Volume urine day (fluid ingested metabolic
water produced) - (evaporative loss from lung
sweat loss loss in the feces)
nephrons vary - several hundred in lower
vertebrates, many thousand in a small mammal to
more than a million in humans
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Nephrons   Two types - juxtamedulary nephrons
- glomeruli in the inner cortex - have the
long loops of Henle that go deep into the
medulla - cortical nephrons - glomeruli are in
the outer cortex - only have short loops of
henle that only extend a short distance into
the medulla Loop of Henle - key to making a
concentrated urine - found only in birds and
mammals  
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Kidneys - kidneys filter the blood plasma and
then reabsorb needed substances back into the
blood - substances left behind are secreted in
the urine Three processes contribute to the
final urine composition 1. Filtration - - form
an ultrafiltrate in the lumen of Bowmen's
capsule 2. Tubular reabsorption - reabsorb
almost 99 of water and most of the salts 3.
Tubular secretion - most by active transport
mechanism - some (nitrogenous wastes) through
synthesis in the tubules themselves
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Glomerular filtration   humans - 15-25 of the
water and solutes are removed from the
plasma 125 ml/min (180L/day)   GFR depends on
three factors 1. Hydrostatic pressure
difference (glomerular capillaries to
Bowman's capsule) 2. Colloid osmotic pressure
of the blood plasma (opposes filtration) 3.
Hydraulic permeability (sieve-like properties
of the three-layered filter)
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Willmer 5.10
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How do we regulate this glomerular filtration
rate? - Hydrostatic pressure difference
primary source of resistance to provide the
hydrostatic pressure is efferent arterioles
and the capillaries of the vasa recta -
colloid osmotic pressure - tends to be
constant under most conditions - dehydration
- burn victims
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Regulation of GFR 1. Intrinsic myogenic
response of the afferent arterioles -
intrinsically restrict to an increase in blood
pressure 2. Juxtaglomerular apparatus
macula densa cells - monitor osmolarity and
flow of fluid in distal tubule - release a
variety of factors - paracrine granular or
juxtaglomerular cells - modified smooth
muscle cell in the wall of the afferent
arteriole - secrete renin - locally and
systematically - Ang II 3. Sympathetic
innervation - induces contraction of
glomerulus - closing down filtering
capillaries - thus reducing surface area
available for filtration
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Tubular reabsorption Humans   180 liters of
filtrate - l liter of urine 99 of filtered
water reabsorbed 99 of the NaCl reabsorbed
(1800 g filtered, 10 g excreted) glucose -
small, freely filtered - completely
reabsorbed in normal individuals - loss is
equivalent to losing chemical energy from the
organism
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Transport in the proximal tubule
passive
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Proximal tube - starts the process of
concentrating the urine - 70 of the Na is
removed from the lumen - a proportional amount
of Cl-, water and other solutes follow - about
75 of the filtrate is reabsorbed - fluid is
iso-osmotic with respect to plasma and
interstitial fluids - water transport is coupled
to active sodium transport   Filtrate that
reaches the distal portion of the proximal
tubule - 1/4 its original volume - substance
not taken up by active transport or do not
passively diffuse have been concentrated 4
fold ( we are iso-osmotic though)   - all of
this is due to active transport of Na -glucose,
amino acids absorbed using the Na
electrochemical gradient
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Structure of cells in the proximal tubule
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Loop of Henle   Descending limb - - made up of
very thin cells that have very few
mitochondria - they have no brush border, no
active Na transport - have very low permeability
to NaCl and urea - modest water
permeability   Thin segment of the ascending
limb - similar features as the descending limb
- except it is highly permeable to NaCl -
permeability to urea and water is low   Thick
ascending limb - actively transport Na outward
from the lumen to the interstitial space -
very low permeability to water - result -
fluid reaching the distal tubule is hypo-osmotic
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How do we make a concentrated urine? -water is
removed from the urine as it passed through the
collecting duct - only those vertebrates that
have a loop of Henle can make a hyperosmotic
urine - degree to which the urine cam be
concentrated is proportional to the length of the
loop of Henle desert dwellers such as the
kangaroo rat have the longest loops   - related
to this ability to concentrated urine, it was
observed that osmolarity of the interstitial
fluids of the medulla progressively increase as
it moves deeper towards the renal pelvis.
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What is a counter current multiplier? -
mechanism for concentrating - chemical, heat
Two major components - single effect -
multiplied effect   Primary features 1.
Standing concentration gradient set up is
dependent on both the single effect and the
multiplier effect operating. 2. Difference from
one end of the limb (loop) to the other is far
greater than the difference separating the limbs
of the loop 3. Requires asymmetry - net
transport of Na in one direction.
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How do marine birds maintain their osmotic
balance without access to fresh water? Knut
Schmidt_Nielsen - 1957   Nasal gland capable of
secreting a hypertonic solution of NaCl Found
also in reptiles , marine iguana, sea snakes ,
marine turtles Crocodiles - salt gland in the
tongue
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Ammonotelic - excrete NH3 or NH4   -teleost
and aquatic invertebrates cell membranes are
generally permeable to unionized ammonia
(NH3) - not very permeable to NH4 (ammonium
ions) - most ammonium excretion occurs via
passive diffusion of NH3 - teleosts Transport
of amino groups  transfer amino groups to
alpha-ketoglutarate to make glutamate go to
gills - reverse go to liver - make into
glutamine - less toxic mammals - glutamine is
transported to kidney - deaminated in the
cell of the kidney tubules - ammonia is
released into lumen and excreted as NH4
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Problem with NH3 and NH4 highly toxic
(lethal at 50 mM in most mammals) - elevates
pH - substitutes for K ions in many
reactions Positive - highly soluble - cheap
 
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Ureotelic - urea -excreting animals   - urea
- very soluble - membranes are relatively
impermeable to urea - need a transport
protein - far less toxic than ammonia - requires
much less water - contains two nitrogen per
molecule - made by the ornithine-urea cycle in
most vertebrates (teleosts) - occurs in the
liver Two NH2 groups and one CO2 are added to
ornithine to make a molecule of arginine
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Elasmobranch us the ornithine cycle Nucleic
acid catabolism teleost and many marine
invertebrates use the uricolytic pathway -urea
is produce from uric acid - uric acid comes from
the transamination of aspartate or other nucleic
acid  
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Uricotylic excretion of nitrogenous
wastes Birds, reptiles, most terrestrial
arthropods   Excretory product - uric acid or
guanine - carries four nitrogens per molecule -
lack uricase - can't break it down - poorly
soluble - readily precipitates - requires very
little water to get rid of - best solution for
conditions of limited water availability -
expensive
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