Lectures 21 and 22, 12 and 18 Nov 2003

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Lectures 21 and 22, 12 and 18 Nov 2003 Chapter
14, Osmoregulation and Kidney Function Vertebrat
e Physiology ECOL 437 University of Arizona Fall
2003 instr Kevin Bonine t.a. Bret Pasch
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Vertebrate Physiology 437
1. Osmoregulation Kidney Function
(CH14) 2. Announcements -Peer reviews due
Thurs. -Eldon Braun Thurs.
(14-18)
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Name that student
Cody_Diehl Insulin Resistance and Muscle
Metabolism Research
Derek_Dindal MCB...
Krystal_Rotty Marine Bio Interests?
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A reminder for all that this Friday (14th) at
Doings we will be hearing from Brett Graham -- a
Doctoral student in the lab of Rob Callister,
Dept of Anatomy and Neuroscience, at The
University of Newcastle, Australia. The title of
Brett's talk is Use of the patch-clamp recording
technique in vivo. Hope you can all come to what
promises to be yet another great Doings. Gould
Simpson 601 4pm.
Exam 3 next week!
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Finding Nemo (marine adaptations and attempted
trophic interactions) VS. Princess Bride (pain
receptors and endocrine systems gone awry)
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Rubin and Ed A complex tale about two republicans
hell-bent on burying a frozen cat.
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How does ram ventilation work?
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Osmoregulatory Mechanisms
Apical surface (faces lumen and outside world)
Basal surface (faces body and extracellular fluid)
- Active movement of ions/salts requires ATP -
Movement of water follows movement of ions/salts
(14-11)
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Gradients established and usedto move ions, water
active
passive
(14-12)
Mammalian Kidney
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Fish Gills
Chloride cells involved in osmoregulation
-(recall Pelis et al. paper on smolting)
-lots of mitochondria to power ATPases
-mechanism similar in nasal glands (birds
and reptiles), and shark rectal gland
(14-14)
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(14-17)
Kidney Functions

• Osmoregulation
• Blood volume regulation
• Maintain proper ion concentrations
• Dispose of metabolic waste products
• pH regulation (at 7.4)
• Dispose of toxins and foreign substances

How does the kidney accomplish this?
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Mammalian Kidney
(14-17)
-Paired
-1 body mass -20 blood flow
-urine contains water metabolic
byproducts (e.g., urea) excess salts etc.
-from ureter to urinary bladder (smooth muscle,
sphincter, inhibition) -out via urethra during
micturition
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Mammalian Kidney Anatomy
FUNCTIONAL UNIT ( 1 million)
(14-17)
Urine
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Nephron Anatomy
1 -Proximal tubule 2 -Loop of Henle
-descending -ascending 3 -Distal tubule
-numerous nephrons empty into collecting duct
-collecting ducts empty into renal pelvis
(14-18)
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Nephron Anatomy
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Knut Schmidt_Nielsen 1997
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Vasa recta
Countercurrent exchange
Knut Schmidt_Nielsen 1997
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Kidney Processes- overview
1. FILTRATION blood --gt filtrate
2. REABSORPTION filtrate --gt blood
3. SECRETION blood --gt filtrate
All 3 involved in final Urine Composition
(14-21)
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Filtration plus secretion
U/P
Mosm x1000

Dipodomys
Knut Schmidt_Nielsen 1997
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Humans 125 ml/min or 180 L/day
(14-20)
Sympathetic innervation tends to constrict
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Filtration
Bowmans capsule 3 layers 1. Glomerular
endothelial cells -100x leakier than other
capillary walls 2. Basement membrane -negativel
y charged glycoproteins -repel plasma proteins
by charge 3. Epithelial cells -podocytes
create slits
Filtrate protein-free and cell-free plasma
Glomerular Filtration Rate (GFR) Humans 125
ml/min or 180 L/day (60x plasma vol.)
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Bowmans capsule
(14-23)
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Bowmans capsule
proteins and larger molecules remain
About 20 of the plasma and solutes that enter
glomerulus end up in BC
(14-22)
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Bowmans capsule
1. Starvation Implications?
2. Kidney Stone Implications?
(14-22)
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Filtration Regulation
1. Myogenic props. of afferent arteriole resist
stretch
2. Secretions from cells of juxtaglomerular
apparatus (where distal tubule passes near
bowmans capsule)
-Macula densa cells (distal tubule) -monitor
osmolarity and flow in distal tubule -paracrine
hormonal activity on afferent arteriole
-Granular or juxtaglomerular cells (afferent
arteriole) -release renin which alters blood
pressure
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(14-24)
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Filtration Regulation
Renin (from granular cells) released in response
to -low renal BP, -low solute in distal
tubule, -or sympathetic activation Renin
leads to activation of Angiotensin II
which causes systemic vasoconstriction to inc.
BP stimulates aldosterone from adrenal
cortex vasopressin (ADH) from post.
pit. (these promote salt, water reabsorption)
3. Sympathetic innervation (reduce
GFR) -afferent vasoconstriction -decreased
space between podocytes
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Renal Clearance
Volume of plasma cleared of a substance by the
kidney. (Filtration, Reabsorption,
Secretion) Inulin (GFR) b/c neither reabsorbed
nor secreted If clearance gt GFR secretion If
clearance lt GFR reabsorption (More on page
603.)
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1. FILTRATION blood --gt filtrate
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2. REABSORPTION filtrate --gt blood
3. SECRETION blood --gt filtrate
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Knut Schmidt_Nielsen 1997
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Reabsorption
of 180 L/day filtered, 178.5 L reabsorbed in
humans
Lots of active transport of salts and other
substances
Tight junctions not so tight in proximal tubule,
so water can move from filtrate to plasma
Because of reabsorption (and secretion), Renal
clearance does NOT often equal GFR
(14-19)
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Reabsorption limit Glucose example
Tm at 300 mg/min/100ml plasma
Transport maximum
Carrier-mediated transport
(14-25)
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(14-27)
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Reabsorption
Proximal Tubule 70 filtered Na actively
reabsorbed (by Na/KATPase pump in basolateral
membrane) Cl- and water follow 75 of filtrate
is reabsorbed including glucose and amino acids
(Na dependent) also, phosphates, Ca,
electrolytes as needed Parathyroid hormone
controls phosphate and Ca reabsorp. triggers
calcitriol production (Vit. D) for Ca
At end of proximal tubule filtrate is isoosmotic
with plasma (300mOsm) however, remaining
substances are 4x concentrated
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Gradients established and used
active
passive
(14-12)
Mammalian Kidney
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Gradients established and used
passive
active
passive
Symporters
(14-13)
Mammalian Kidney
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Reabsorption
Countercurrent multiplier
Loop of Henle Descending limb -no active NaCl
transport -low urea and NaCl permeability -perme
able to water Ascending thin limb -no active
NaCl transport -but permeable to NaCl -low urea
permeablity -low water permeability Ascending
thick limb -NaCl transported out of tubule -low
water permeability
One driver of concentrating mechanism of nephron
Knut Schmidt_Nielsen 1997
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Reabsorption
(14-18)
Distal Tubule -K, H, NH3 into tubule -under
endocrine control -Na, Cl-, HCO3- back into
body -water follows (Na reabsorption
facilitated by aldosterone)
Angiotensinogen Renin Ang. I ACE in lung Ang.
II aldosterone from adrenal cortex
ADH from post. pit.
Collecting Duct -permeable to water -hormone
control (ADH/vasopressin) -water (via
aquaporins) follows osmotic gradient
-permeable to Urea in inner medulla
Another driver of concentrating mechanism of
nephron
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-ADH role in water reabsorption/urine
concentration
-Renin -gt Ang. II -gt ADH
-Baroreceptor input (atrial and arterial)
(p.279)
-EtoH inhibits ADH release
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Atrial Natriuretic Peptide (ANP) -released by
atrium cells in response to stretch
(elevated BP) -opposite effect of
renin-angiotensin system -decreases sodium
reabsorption -therefore increased urine
production -ANP inhibits release of ADH, renin,
aldosterone
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ADH acts in stippled region of collecting duct
Urine can be 100-1200 mOsm in humans (plasma
about 300)
(14-28)
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Secretion
From plasma into tubule of nephron
K, H, NH3, organic acids, organic bases
Organic anions (OA-)
Liver conjugates toxins and waste to glucuronic
acid
Secreted into tubule lumen and excreted
Na/K-ATPase
(14-30)
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Secretion
-K secretion if, and only if, Na reabsorption
(Na/K-ATPase) -Can lead to unfavorably
low levels of K if aldosterone acting to
reabsorb Na or
-High K levels can affect heart function so
excess stored in tissue as result of insulin
action
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Urine concentrating ability
ADH acts in stippled region of collecting duct
Urine can be 100-1200 mOsm in humans (plasma
about 300)
(14-28)
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Same story, different picture
Knut Schmidt_Nielsen 1997
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Urine concentrating ability
1200 mOsm in humans 9000 mOsm on kangaroo
rats 9600 mOsm in Perognathus (mouse)
sum
-Length of loops of henle -Corticomedullary
concentration gradient
(14-33)
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Urine concentrating ability
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-Active Countercurrent Multiplier
-Dynamic
-Vasa Recta
Some urea recycled
Cortex and outer medulla
(14-34)
Inner medulla
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Urine concentrating ability
-Vasa Recta
-See Review of Urine Formation on page 614
-Loops of Henle only in Mammals and Birds -gt
Hyperosmotic Urine
(14-18)
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Osmoregulatory Mechanisms
-Similar mechanisms in nasal salt glands of birds
and reptiles, mammalian kidney, rectal glands of
sharks, gills of marine fishes, etc. -Regulated
by similar hormones as well.
(protons, Na/K, symporters)
(14-11)
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pH regulation
(14-17)
Acid Secretion
CO2 via lungs, H via kidneys (skin and gills
can also play role)
Proximal tubule and loop of henle Na/H
antiporter (driven by Na/K-ATPase)
Distal tubule and collecting duct A-type cells
with proton pump and anion exchanger
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proton pump
anion exchanger
(14-31)
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Ultrafiltrate buffered by bicarbonate,
phosphates, and ammonia allowing for more acid
secretion e.g., NH3 H ? NH4
if low on ammonia, deaminate amino acids
(14-32)
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pH regulation
Base Secretion (opposite A-type cells)
proton pump
anion exchanger
(14-31)
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Gradients established and used
Antiporter to get rid of protons (acid) and gain
Na
active
passive
(14-13)
Mammalian Kidney
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Non-mammalian kidneys
-Only birds also have loops of henle
-Freshwater fish with more and larger glomeruli
to make lots of dilute urine
-Some marine fish without glomeruli or bowmans
capsule urine formed by secretion, ammonia
secreted by gills
-Osmoregulation also via extrarenal organs
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Salt Secretion
recycle
active
Down electrochemical gradient
(Paracellular)
(14-14)
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Salt Glands
Shark rectal glands to dispose of excess NaCl
-blood hyperosmotic to seawater, but less
salt -more urea and TMAO (trimethylamine oxide)
-NaCl actively secreted
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Shark Rectal Salt Glands
(14-36)
Salt-secreting cells -Na/K-ATPase pump in
basolateral membrane -generates
gradient for Na by which Na/2Cl-/K
cotransporter drives up Cl- in cell
-Cl- across apical membrane -Na follows
paracellularly down electrochemical
gradient (and H2O) -apical membrane
impermeable to urea and TMAO
-therefore iso-osmotic secretion with
lots of NaCl
slightly different in birds and lizards ?
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(14-36)
Salt Glands
Nasal/orbital salt glands of birds and reptiles
-especially species in desert or marine
environments.
Hypertonic NaCl secretions (2-3x plasma
osmolarity)
Allows some birds to drink salt water and end up
with osmotically free water
Amblyrhynchus cristatus
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Fish Gills
Chloride cells involved in osmoregulation
-(recall Pelis et al. paper on smolting)
-lots of mitochondria to power ATPases
-mechanism similar in nasal glands (birds
and reptiles), and shark rectal gland
(14-14)
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Freshwater fish The mechanism basically reversed
to allow uptake of salt from water against
concentration gradient
Na/K-ATPase to generate Na gradient
proton pump to create electrical gradient
(14-31)
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(recall Pelis et al. paper on smolting)
Sea ?? Freshwater
Switch between getting rid of excess salt in
seawater and taking up salt in freshwater
Growth hormone and cortisol for ? sea (more
active chloride cells with more
Na/K-ATPase activity)
Prolactin for ? freshwater
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END