Lectures 21 and 22, 12 and 18 Nov 2003Chapter 14, Osmoregulation and Kidney Function

Vertebrate PhysiologyECOL 437

University of ArizonaFall 2003

instr: Kevin Boninet.a.: Bret Pasch

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Vertebrate Physiology 437

1. Osmoregulation Kidney Function (CH14)

2. Announcements… -Peer reviews due Thurs. -Eldon Braun Thurs.

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Osmoregulation by Birds

Eldon J. BraunDepartment of PhysiologyUniversity of Arizona

(14-18)

Name that student:3

Cody_Diehl

Insulin Resistanceand MuscleMetabolismResearch

Derek_Dindal

MCB...

Krystal_Rotty

Marine BioInterests?

Exam 3 next week!

4A reminder for all that this Friday (14th) at Doings we will be hearing from Brett Graham -- aDoctoral student in the lab of Rob Callister, Dept of Anatomy and Neuroscience, at TheUniversity of Newcastle, Australia. The title of Brett's talk is: Use of the patch-clamprecording technique in vivo. Hope you can all come to what promises to be yet another greatDoings. Gould Simpson 601 4pm.

Finding Nemo(marine adaptations and attempted trophic interactions)

VS.

Princess Bride(pain receptors and endocrine systems gone awry)

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Rubin and EdA 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 MechanismsApical 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 used…to move ions, water

(14-12)

active

passive

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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2

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5

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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?

13(14-17)

(14-17)Mammalian Kidney-Paired-1% body mass-20% blood flow

-from ureter to urinary bladder(smooth muscle, sphincter, inhibition)

-out via urethra during micturition

-urine contains: water metabolic byproducts (e.g., urea) excess salts etc.

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(14-17)

Mammalian Kidney Anatomy

FUNCTIONAL UNIT(~ 1 million)

Urine

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(14-18)

-numerous nephronsempty into collecting duct

-collecting ducts emptyinto renal pelvis

1 -Proximal tubule2 -Loop of Henle -descending -ascending3 -Distal tubule

16Nephron Anatomy

Knut Schmidt_Nielsen 1997

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3

4

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7

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Nephron Anatomy

Knut Schmidt_Nielsen 1997

Vasa recta

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Countercurrentexchange

(14-21)

1. FILTRATIONblood --> filtrate

2. REABSORPTION filtrate --> blood

3. SECRETION blood --> filtrate

All 3 involved in finalUrine Composition

Kidney Processes- overview19

Knut Schmidt_Nielsen 1997

Filtration plus secretionU/PMosm = x1000

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+

Dipodomys

(14-20)

Sympatheticinnervation tendsto constrict

Humans:125 ml/min

or180 L/day

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Filtration:

Bowman’s capsule3 layers1. Glomerular endothelial cells

-100x leakier than other capillary walls2. Basement membrane

-negatively charged glycoproteins-repel plasma proteins by charge

3. Epithelial cells-podocytes create slits

Glomerular Filtration Rate (GFR)Humans: 125 ml/min or 180 L/day (60x plasma vol.)

Filtrate = protein-free and cell-free plasma

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Bowman’s capsule

(14-23)

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(14-22)

proteins andlarger moleculesremain

About 20% of the plasmaand solutes that enterglomerulus end up in BC

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Bowman’s capsule

(14-22)

1.StarvationImplications?

2.Kidney StoneImplications?

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Bowman’s capsule

Filtration Regulation:

1. Myogenic props. of afferent arteriole resist stretch

2. Secretions from cells of juxtaglomerular apparatus(where distal tubule passes near bowman’s 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:

3. Sympathetic innervation (reduce GFR)-afferent vasoconstriction-decreased space between podocytes

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 whichcauses systemic vasoconstriction to inc. BPstimulates aldosterone from adrenal cortex

vasopressin (ADH) from post. pit.(these promote salt, water reabsorption)

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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 > GFR = secretionIf clearance < GFR = reabsorption

(More on page 603.)

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Knut Schmidt_Nielsen 1997

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301. FILTRATION

blood --> filtrate

2. REABSORPTION filtrate --> blood

3. SECRETION blood --> filtrate

Reabsorption:

of 180 L/day filtered, ~178.5 L reabsorbed in humans

Tight junctions not so tight inproximal tubule, so water canmove from filtrate to plasma

(14-19)

Lots of active transport ofsalts and other substances

Because of reabsorption(and secretion),Renal clearance doesNOT often equal GFR

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Reabsorption limit – Glucose example

(14-25)

Transportmaximum

Tm at 300 mg/min/100ml plasma

Carrier-mediatedtransport

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Reabsorption:

Proximal Tubule70% filtered Na+ actively reabsorbed

(by Na+/K+ATPase pump in basolateral membrane)Cl- and water follow

75% of filtrate is reabsorbedincluding 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

(14-27) 33a

Gradients established and used:

(14-12)

active

passive

Mammalian Kidney

33b

Gradients established and used:

(14-13)

passive

passive

active

Mammalian Kidney

Sympo

rters

33c

Reabsorption:

Loop of HenleDescending limb

-no active NaCl transport-low urea and NaCl permeability-permeable 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 ofconcentratingmechanism of

nephron

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Knut Schmidt_Nielsen 1997

Countercurrentmultiplier

Reabsorption:

Angiotensinogen Renin Ang. I ACE in lung Ang. II aldosterone from adrenal cortex

Distal Tubule-K+, H+, NH3 into tubule-under endocrine control-Na+, Cl-, HCO3

- back into body-water follows (Na+ reabsorption facilitated by aldosterone)

Collecting Duct-permeable to water-hormone control (ADH/vasopressin)-water (via aquaporins) follows osmotic gradient

-permeable to Urea in inner medulla

ADH from post. pit.

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Another driver ofconcentrating

mechanism of nephron

(14-18)

(p.279)

-ADH role in waterreabsorption/urine concentration

-Renin -> Ang. II -> ADH

-Baroreceptorinput (atrial andarterial)

-EtoH inhibitsADH 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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(14-28)

ADH acts instippled region ofcollecting duct

Urine can be 100-1200 mOsmin humans (plasma about 300)

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Secretion:

From plasma into tubule of nephron

K+, H+, NH3, organic acids, organic bases

(14-30)

Organic anions (OA-):

Liver conjugatestoxins and wasteto glucuronic acid

Secreted intotubule lumen andexcreted

Na/K-ATPase

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Secretion:

-K+ secretion if, and only if, Na+ reabsorption (Na/K-ATPase)

-Can lead to unfavorably low levels of K+ ifaldosterone acting to reabsorb Na+

or

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-High K+ levels can affect heartfunction so excess stored in

tissue as result of insulin action

(14-28)

ADH acts instippled region ofcollecting duct

Urine can be 100-1200 mOsmin humans (plasma about 300)

Urine concentrating ability42

Knut Schmidt_Nielsen 1997

Same story,different picture

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Urine concentrating ability

(14-33)

1200 mOsm in humans9000 mOsm on kangaroo rats9600 mOsm in Perognathus (mouse)

-Length of loops of henle-Corticomedullary concentration gradient

sum

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(14-34)

Cortex andouter medulla

Inner medulla

-ActiveCountercurrentMultiplier

-Dynamic

Some urea“recycled”

-Vasa Recta

Urineconcentratingability

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-Vasa Recta

(14-18)

-Loops of Henle only inMammals and Birds ->Hyperosmotic Urine

-See Review ofUrine Formationon page 614

Urineconcentratingability

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Osmoregulatory Mechanisms-Similar mechanisms in nasal salt glands of birds andreptiles, mammalian kidney, rectal glands of sharks, gillsof marine fishes, etc.-Regulated by similar hormones as well.

(14-11)

(protons, Na+/K+, symporters)

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pH regulation

Proximal tubule and loop of henle: Na+/H+ antiporter (driven by Na/K-ATPase)

CO2 via lungs, H+ via kidneys (skin and gills can also play role)

Distal tubule and collecting duct:A-type cells with proton pump and anion exchanger

Acid Secretion

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protonpump

anionexchanger

(14-31)

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(14-32)

Ultrafiltrate buffered by bicarbonate, phosphates, andammonia allowing for more acid secretion

e.g., NH3 + H+ NH4+

if low onammonia,deaminateamino acids

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(14-31)

pH regulationBase Secretion (opposite A-type cells)

anionexchanger

protonpump

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Gradients established and used:

(14-13)

passive

active

Mammalian Kidney

Antiporterto get ridof protons(acid) andgain Na+

52-54

-Only birds also have loops of henle

Non-mammalian kidneys:

-Some marine fish without glomeruli orbowman’s capsule – urine formed by secretion,ammonia secreted by gills

-Freshwater fish with more and largerglomeruli to make lots of dilute urine

-Osmoregulation also via extrarenal organs…

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Salt Secretion:

(14-14)

active

Down electrochemical gradient(Paracellular)

recycle

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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

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

(14-36)

… slightly different in birds and lizards

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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 withosmotically free water

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Amblyrhynchus cristatus

(14-36)

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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2

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Freshwater fish:The mechanism basically reversed to allow uptake ofsalt from water against concentration gradient

proton pump tocreate electricalgradient

Na/K-ATPaseto generateNa gradient

(14-31)

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Sea Freshwater

Switch between getting rid of excess salt inseawater and taking up salt in freshwater

Growth hormone and cortisol for sea(more active chloride cells with more

Na/K-ATPase activity)

(recall Pelis et al. paper on smolting)

Prolactin for freshwater

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END

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