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    Excretion6/4/08

    Human Biology 1 Excretion

    A. Excretion Notes

    1. Definitions

    Excretion - release of metabolic wastes and excess

    water

    Defecation (or elimination) - the release of unabsorbed

    wastes (e.g., feces) from the digestive tract

    2. Components

    a. Liver

    -excretes bile pigments-bile pigments derived from heme portion of

    hemoglobin, and incorporated into the bile here

    b. Skin

    -perspiration (solution of water, salt, and urea)- helps to maintain body temperature, by cooling

    (evaporation)

    - may also rid body of excess ureac. Large Intestines

    -excretes Calcium and Iron salts-defecation

    d. Kidney

    - ammonia, a toxic by-product of metabolism ofproteins is converted to urea in the liver, which isexcreted here

    -hypothalamus regulates function with hormones- ADH raises the osmotic concentration within

    kidney, and so promotes the reabsorption ofwater

    - Aldosterone stimulates sodium ion reabsorptione. Lungs

    - CO2, and water3. Key Definitions

    a. Kidney

    - the organ the filters the blood (600 L/day) toremove nitrogenous wastes and regulates the

    balance of water and solutes in the blood plasma.

    - Cortex

    Text Diagram:Kidney

    Generally speaking,o Hormones aresecreted.o Wastes are excreted.

    and

    o Bile issecretedand/orexcreteddepending on yourpoint of view.

    Intake of water

    o Drink 1500ml/dayo Food 1000ml/dayo

    Metabolism 200-350ml/day

    Excretion of water

    o Lungs 500ml/dayo Skin 400ml/dayo Feces 200ml/dayo Urine 1600ml/day

    ErythropoietinThe kidneysmake this hormone, whichstimulates the bone (red) marrow tomake blood cells, in response to lowlevels of O2in the blood.

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    - Outer Medulla- Inner Medulla- Renal Pelvis

    - Renal Circulation (abridged pathway)

    Aorta !Renal artery !Afferent arteriole!

    Glomerulus (capillaries)!Efferent arteriole !

    Peritubular capillaries (and vasa recta)!Renal vein!Inferior vena cava

    b. Ureters

    - the tubes (2) carrying urine from the kidneys to thebladder

    c. Bladder

    - stores urine, prior to eliminationd. Urethra

    - the tube carrying urine from the bladder to the exteriorof the body

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    4. The Nephron

    - the functional unit of the kidney; one of numeroustubules (about a million) involved in filtration andselective reabsorption of blood. Each one consists of aBowmans capsule, an enclosed glomerulus, and arenal tubule

    Arterioles

    - Afferent arteriole

    Text Diagram:Nephron

    Adrenal Gland

    - Adrenalin medulla- Aldosterone - cortex

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    - Juxtaglomerular apparatus- leads into Glomerulus

    - Efferent arteriole- exits glomerulus- Tubular excretion (secretion)- Peritubular capillaries!venule!vein

    Peritubular Capillaries

    - takes up reabsorbed material, and drains into the Renalvein

    - helps maintain concentration gradient in the medullafor reabsorption

    Glomerulus (L. little ball)- a cluster of capillaries enclosed by the Bowmans

    capsule.

    Bowmans Capsule- the bulbous unit of the nephron, which surrounds the

    glomerulus. The kidney works by forced filtration,

    blood pressure driving blood plasma from theglomerular capillaries into the Bowmans capsule,

    after which it passes through thenephron, where most

    water and ions are reabsorbed into the bloodstream

    and the residue is excreted as urine- filtrate

    Glomerular (Pressure) Filtration of Blood

    - blood plasma is forced, under pressure, out of theglomerular capillaries into the Bowmans capsule,

    through which it enters the renal tubule; the filtrate

    contains water and ions (which are recovered) andmetabolic wastes (which are eliminated as urine), but

    not red blood cells or large proteins, which are too

    large to pass through the glomerular capillary wall.

    Proximal Convoluted Tubule (PCT)

    - Tubular (Selective) Reabsorptiono Glucose (100%), a.a. (100%), bicarbonate

    (80-90%), water (65%), Na+

    (65%)

    Distal Convoluted Tubule (DCT)- Tubular Secretion (Excretion)

    o H+, K+, creatine, ammonia, uric acid,penicillin, estrogen/progesterone

    o Many organic acids and bases (either end-products of metabolism or exogenous)

    Juxtaglomerular apparatus

    - is located between the DCTand the afferent ar teriole

    - note the variation in thisdiagramit is actually a morerealistic image than thesplayed open image generally

    used to label the parts on theprovincial exam, and seen onthe previous page.

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    o Anions:" Endogenous: Urate, Oxalate" Exogenous: Penicillin, Salicylates

    o Cations:" Creatinine Quinine, Dopamine, Adrenaline /

    Epinephrine Isoproterenol

    -Aldosterone, increased reabsorbtion of Na+(excretionof K+) and water along the ascending limb and arch)

    Collecting Duct (CD, CT)

    - ADH, increased permeability to water, results inincreased water reabsorption

    - Aldosterone, increased permeability to salt (Na+),results in increased salt (Na+) reabsorption

    o Side affect increased reabsorption of watero Increased excretion of K+in urineo Co-transport of Cl-, HCO3-, H+.

    - drains into the Renal Pelvis!ureter!bladder!urethra

    5. How The Kidney Works- The human kidney achieves a high degree of water

    reabsorption by using the salts and urea in the

    glomerular filtrate to increase osmotic concentration of

    the kidney tissue. This facilitates the movement ofwater from the filtrate out into surrounding tissue,

    where it is collected by blood vessels impermeable tothe high urea concentration but permeable to water.

    - as such human urine may be as much as 4.2 times asconcentrated as blood plasma, dessert animals such as

    the gerbil are even higher, 14 times.

    - the kidney uses the hairpin loop of Henle to set up acountercurrent flow. The longer the loop the greater

    the water reabsorption. The countercurrent processesinvolves the passage of two solutes across the

    membrane of the loop: salt (NaCl) and urea.

    - basically then the kidney is divided into two zones:1.The outer portion, cortex, contains the upper

    portion of the loop including the upper ascending

    arm where reabsorption of salt from the filtrate byactive transport occurs

    Tubular SecretionThis is an essential mechanism forremoving unwanted substances from theplasma. Substances such as H+, K+,

    creatine, NH4+, and certain organic acids

    move from the blood of the peritubularcapillaries through the tubule cells, or

    from the tubule cells themselves into thefiltrate. Tubular secretion is essential for:

    o Removal of substances notalready in the filtrate, such ascertain drugs;

    o Removing unwanted substancesor metabolic waste productssuch as urea and uric acid,which have been reabsorbed by

    passive processes;

    o Removal of excessive K+; ando Controlling blood pH.

    If blood becomes acidic, the renal tubule

    cells actively secrete H+(at DCT) intothe filtrate and retain more HCO3

    -(at

    PCT), and K+. By contrast, if bloodbecomes alkaline, Cl-is reabsorbed andmore HCO3

    -leaves the body in the urine.

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    2.The inner portion, medulla, contains both the lower

    portion of the loop and the bottom of the collecting

    duct, which is permeable to urea

    - the active reabsorption of salt in the cortex drives theprocess. Salt reabsorption from the filtrate of one arm

    of the loop establishes a gradient of salt concentration,

    with concentration higher in the medulla at the bottomof the loop. It is the high salt concentration that raises

    the total osmotic concentration so high that water

    passes by osmosis out the collecting duct.

    6. Nitrogenous Wastes

    - Deamination occurs in the liver- enzymes break down amino acids by removing

    the amino group(NH2), and combine with H+

    ions to form ammonia(NH3); (the remainder of

    the amino acid is converted to sugar or lipid.)

    - Ammoniais toxic to all cells, therefore it must beremoved from the body

    - but even low concentrations can kill cells,therefore it is necessary to transport it in very low

    concentrations

    -

    Humans and most mammals detoxify ammoniabyconverting it to urea in the liverwhich is far lesstoxic, and can be transported at far higherconcentrations

    - the urea is carried by the blood stream to thekidneys, where it is excretedas the principalcomponent of urine

    7. The Kidney As Regulator Organ- The Kidney helps regulate the composition of the

    blood

    -and therefore also internal body chemistry

    -by selectively removing substances from the blood,it can control concentrations of ions and other

    chemicals

    - while most amino acids are retained in the kidneys,almost half of the urea entering the blood is

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    eliminated- glucose not normally eliminated, is lost by

    diabetics

    - concentrations of H+, Na+, K+, Cl-, Mg++, Ca++,and HCO3-are maintained

    -this then serves to maintain a constant blood pH

    8. Hormones and Homeostasis- The kidney is concerned with homeostasis

    -regulation is controlled by the central nervoussystem

    - voluntary, autonomic, and hormonal controls- the body requires that the osmotic concentrationof

    blood be maintained within a narrow margin-for this reason it is not always desirable for your

    body to retain the same amount of water

    - affects ion concentration- e.g., if there is too much salt, the kidney

    can,i. dilute it by reabsorbing more water by

    producing more ADH

    ii. reabsorb less salt by decreasing theproduction of Aldosterone

    a. Water Balance (Osmoregulation)

    - Antidiuretic hormone (ADH) aka vasopressinregulates the volume of water excreted by the

    kidneys.- ADH increases the permeability of the distal

    convoluted tubuleand the collecting ductto

    water.

    - ADH is produced in hypothalamusanddescends along nerve fibres to the posterior

    pituitary, where it is stored for subsequent- release

    - Its secretion is regulated by the osmolality of thebody fluids and the blood volumeandpressure.

    - Changes in body fluid osmolality of a fewpercent are sufficient to significantly alter

    ADH secretion.

    Review: What is Albumin?

    - made in the liver, a key plasmaproteinresponsible formaintaining the osmotic pressure

    in the blood.- cf. Digestive system notes

    Hormones:

    - Antidiuretic Hormone (ADH)which stimulates passive waterreabsorption

    - Aldosteronewhich stimulates activesodium reabsorption

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    - Decreases in blood volumeandpressureof 10% to 15% or more are

    needed to effect ADH secretion.

    - The blood volume and pressure sensors are found inthe large pulmonary vessels, the carotid sinus, and the

    aortic arch. These baroreceptors (stretchreceptors) respond to stretch of the vessel wall,

    which in turn is dependent on blood volume andpressure.

    If Too Much Water:

    - osmoreceptors in the hypothalamus detect thedecrease in blood solute concentration (osmolality)

    and lessen the hypothalamus output of ADH

    - baroreceptors/stretch receptors- in the pulmonary vessels, carotid and aortic arch

    detect expansion of the vessel with increasedreabsorption of watersignaling a decrease inADH production

    If Too Little Water:

    - ADH release is increased- by high blood osmolalityaffecting

    hypothalamic osmoreceptors and

    - by low blood volumeaffecting thebaroreceptors/stretch receptors;

    - low osmolality and high blood volumeinhibit ADH release

    - ADH causes walls of collecting ductstobecome more permeable to water and thus

    permits osmolar equilibration and absorption

    of water into the hypertonicmedulla;- a small volume of highly concentrated

    (hypertonic) urine is excretedADHmakes the walls of the DCT andcollecting tubule more permeable towaterso that more water will bereabsorbed and less will be excretedwith urine.

    Alcoholinhibits ADH, decreasing the

    reabsorption of water, and filling thebladder faster, resulting in

    Diuresis, the increased production of

    urine by the kidneyleading to

    increased micturition/ voiding/urination aka #1 or peeing.

    Osmolality:- measure of the solute

    concentration.

    High osmolality means more solute, andless solvent (water).

    Low osmolality means less solute, andmore solvent (water).

    So why is the medulla hypertonic?

    of aldosterone (see notes below)

    - DCT and CD are madepermeable to Na+ which floodthe medulla

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    Source: VPL Science Librarian

    b. Salt Balance

    - for various reasons thesalt levelsin your bloodmust not vary widely; although intake may vary

    - when sodium ion levels drop in association withlow blood volume(low blood pressure), the

    hormone Renin stimulates the adrenal cortex

    increases production of aldosterone

    - a steroid hormone that stimulates activesodium (and water) reabsorption

    - via the:- DCT (ascending limb and arch)and CD

    - Juxtaglomerular apparatus contact between theafferent arteriole and DCT

    - when blood volume (and blood P) drops,- detected bystretch receptors

    Aldosteronecauses Na+to be

    reabsorbed at the DCT (~4%) slightly

    more than at the CD (~3%).- Drawing water, HCO3-(of

    neg. charge, as with Cl-)- And excreting K+

    - Na+is actively reabsorbed atthe PCT, DCT and CD

    - Na+ is passivley reabsorbed atthe ascending loop of Henle

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    (osmorecepotors) in the Juxtaglomerularapparatus i.e., reduced stretch ofJuxtaglomerular cells

    - and glomerular (pressure) filtration decreases theJuxtaglomerular apparatus secretes Renin

    -

    Renin- (changes angiotensinogen [a plasma protein fromthe liver] into angiotensin Iwhich then becomesangiotensin II, a vasocontrictor that also)

    - stimulates the adrenal cortex to secretealdosterone

    - The reabsorption of Na+is followed by thereabsorption of water. Therefore, blood volume andblood pressure increase.

    - Byproduct is the co-transport of Cl-, HCO3-, H+, andK+(although, generally K+are more likely to flowingin the opposite direction, excreted with the urinebecause of aldosterone).

    - Na+have a positive charge, attracting negativelycharged Cl-. Thus, the Cl-follow the Na+out of theLoop and into surrounding tissue.

    - In the transport of Na+/K+ (pump), 3 Na+move outof the tubule (are reabsorbed) for every 2 K+thatgets pulled into the tubule (are excreted).

    - Because of the (hypertonic) concentration gradient setup by aldosterone, water, will also be reabsorbed (cf.

    ADH)

    Source: VPL Science Libarian

    - Aside:- ANH (Atrial Natriuretic Hormone)

    - akaANP(Atrial Natriuretic Peptide)- Source:Atria (of heart)- Stimulus:cardiac cells stretched due to

    increased blood volume

    Filtered LoadFactors ThatStimulate

    Factors ThatInhibit

    Reabsorbed(%)

    Reabsorption Reabsorption

    Proximaltubule

    67Angiotensin IISympathetic nerves Dopamine

    Loop of Henle 25 Sympathetic nerves

    Distal tubule ~4 Aldosterone

    Collecting

    duct

    ~3 AldosteroneAtrial natriuretic

    peptide (ANP)

    The kidney is also responsible for

    activating vitamin D3.

    A critical anti-cancer vitamin.

    Vitamin D (cholecalciferol) can eitherbe ingested with food or made from 7-

    dehdrocholesterol by the action ofultraviolet light (sit out in the sun andmake vitamin D). The liver convertscholecalciferol into 25-hydroxycholecalciferol and the proximaltubule cells of the kidney convert 25-hydroxycholecalciferol into 1,25-dihydroxycholecalciferol. This is the

    active form of vitamin D3. Vitamin D isvery important to dentistsbecause(along with parathyroid hormone, PTHand calcitonin) it controls many aspectsof calcium metabolism in the wholebody. (Do not confuse regulation ofcalcium metabolism by vitamin D etc.

    with the role of calcium as anintracellular second messenger. Thereare indeed overlaps between theseprocesses, but tread carefully.) VitaminD is involved in stimulating theabsorption of calcium from the diet, inlaying down of calcium into the bone

    and, most importantly (at least from thepoint of view of a dentist) in themineralisation processes involved indentinogenesis and amelogenesis. If youdon't have enough vitamin D as a child

    you get rickets (bendy bones) and badteeth. The traditional illustration of this

    is in Victorian child mineworkers whorarely saw the sun (and probably had apoor diet as well).

    - source: Pete Smith

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    Source: VPL Science Librarian

    - Fcn: inhibits Renin, therefore promotes theexcretion of Na+ (natriuresis),

    - which in turn promotes the excretion of water(and blood P and volume decrease).

    Renin-Angiotensin-AldosteroneSystem

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    + efferent arterioles !peritubular capillaries!(venule) !ultimately to the Renal Vein

    + below the Inner medulla feeding the Ureter is theRenal Pelvis

    Glomerular Filtration Tubular Reabsorption Tubular Secretion (Excretion)

    Ammonia, uric

    acid, H+, penicillin,

    creatine

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    Key Hormones (Simplified)

    Hormone Summary

    Source - Hypothalamus, but stored and released from the posteriorpituitary gland

    Stimulus - Secretion in response to reduced plasma volumeis activated bypressure receptors in the veins, atria, and carotids. (too little water)

    - Secretion in response to increases in plasma osmotic pressureismediated by osmoreceptors in the hypothalamus (too many

    solutes)

    also

    - Angiotensin II (cf. Renin) may stimulate the secretion of ADH

    Antidiuretic

    Hormone (ADH)

    aka Vasopressin*

    Function - Constricts arterioles (increased BP)- Lowers heart rate (associated drop in body temp.)- Increased reabsorption of water

    Source - Adrenal cortexStimulus - Presence of Renin(due to sodium deficiency);

    - Decreased BP(as detected by stretch receptorsin the atria of theheart)

    Aldosterone

    Function - reabsorbs Na+,(and indirectly water)-

    excretes K

    +

    ,- raises blood pressureSource - juxtaglomerular apparatus(between glomerulus and DCT)Stimulus - Low blood volume

    - Decreased salt (NaCl)Renin

    Function Renin activates the renin-angiotensin system by cleavingangiotensinogen, produced by the liver, to yield angiotensin I, which is

    further converted into angiotensin II by ACE, the angiotensin-

    converting enzyme primarily within the capillaries of the lungs.

    Angiotensin II then constricts blood vessels,

    - increases the secretion of ADH and aldosterone, and- stimulates the hypothalamus to activate the thirst reflex, leading to

    increased blood pressure.

    * This is much more complex hormone, potentially having many more functions in the body not directlyrelated to the excretory system.

    What gets Reabsorbed & WhereTubule Segment Substance Reabsorbed Mechanism

    Na+ Active transport

    Virtually all nutrients (glucose,,a.a. , vitamins)

    Active transport (cotransportwith Na+)

    Anions (Cl-,HCO3-) Passive transport(cotransportwith Na+ for HCO3- by activetransport)

    Cations (K+, Mg2+, Ca2+) Passive transport

    Water OsmosisUrea and lipid-soluble solutes Passive diffusion (side effect

    of gradient created bymovement of water)

    PCT

    - Tubular Reabsorption- Selective Reabsorption

    Small proteins Endocytosis (digested to a.a.within tubule cells)

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    Loop of HenleDescending Loop Water Osmosis

    Salt (Na+, Cl-) Passive transport

    Salt (Na+, K+, Cl-) Active transportAscending Loop

    Ca2+, Mg2+ Passive transportNa+ Active transport (Aldosterone)Ca2+ Active transport (PTH)

    Cl- Diffusion,some co-transportw/ Na+ (active)

    DCT

    Water Osmosis (ADH)Na+, Active transport (Aldosterone)Cl-, HCO3- Passive transport (side effect of

    gradient created byaldosterone)

    K+, Cl-, H+, HCO3- Co-tansport w/ Na+ (active)Water Osmosis (ADH)

    Collecting Duct

    Urea Facilitated diffusion (mostremains in the medulla)

    Source: Human Anatomy and Physiology 6ed., E. N. Marieb

    Some Percentages of Reabsorption

    PCT Loop DCT CD

    Water 65% 10-20% ADH & Aldosterone impact

    HCO3- 80-90% * *

    Glucose 100% - - -

    Affected by hormone levels

    o Aldosterone = ~ rest of 7-9%(but more K+is secreted)o ANH = ~0Na+ 65% 25%(ascending)4% (greater) 3% (lesser)

    Cl- 50% 35%~14%(both active & passive; as

    NaCl)

    K+ 55% 30% * (~8%)

    a.a. 100% - - -

    H+ (secreted) - (secreted) *

    NH4+ (secreted) - (secreted)

    Some Drugs (secreted) - (secreted) -Urea ? of 53% - (secreted) ? of 53%

    * Can be reabsorbed or secreted depending on what is required to maintain blood pH

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    Summary of Nephron Function

    Source: Human Anatomy and Physiology 6ed., E. N. Marieb

    SummarySource: Pete Smith (http://www.liv.ac.uk/~petesmif/teaching/notetoc.htm)

    In order to be an efficient blood scrubber, the kidney has got to come into contact with a lot ofblood. It does. The kidney receives 25% of cardiac output, which is about 1200 ml/min or over1700 L/day. Every day the kidney filters 180 L of plasma into the urine and, on an average day,reabsorbs 99.4% of it, leaving a daily urine production of about 1L

    Overall, the kidney is fantastically good at both

    Substance

    (mM)filtered secreted excreted reabsorbed %reabsorbed

    Sodium 26,000 150 25,850 99.4Potassium 600 50 90 560 93.3

    Chloride 18,000 150 17,850 99.2Bicarbonate 4,900 0 4,900 100Urea 870 410 460 53

    Glucose 800 0 800 100Total solute 54,000 100 700 53,400 87

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    (mOsm)Water (L) 180 1 179 99.4

    Each day the kidney filters and reabsorbs an incredible 1.5kg of salt dissolved in 180 L of water.

    The final stage of urine production is storage in the bladder and micturition.

    Summary of ProcessesSource: http://www.bioeng.auckland.ac.nz/physiome/ontologies/urinary/tissues.php

    Glomerular FiltrationIs a passive, non-selective process, where fluids and solutes are driven through a membraneunder hydrostatic pressure. All molecules, with the exception of high molecular mass proteins,are filtered out of the blood flowing through the glomerulus, into the glomerular capsule of therenal tubule.

    Tubular Reabsorption

    Of the ~125 ml of plasma filtered by the glomeruli, 124 ml is reabsorbed during passage throughthe renal tubules. Tubular reabsorption is a transepithelial process carried out in the PT, loop ofHenle, DCT and the collecting ducts. Water, ions and nutrients are reabsorbed either passivelyalong their electrochemical gradients, by simple diffusion, facilitated diffusion, and osmosis, orthey are actively reabsorbed via cotransporters. Cotransporters often couple the free energyreleased by the energetically favourable movement of Na+ along its electrochemical gradient tothe transport of substances such as amino acids and glucose against their electrochemicalgradients.

    To some degree, the entire length of the renal tubule is involved in reabsorption, however, thecells of different regions of the renal tubule are adapted to perform specific transport functions,and consequently, the absorptive capacities of the different regions of the renal tubule differ. Theproximal tubule is the site of most reabsorption.

    Tubular SecretionThis is an essential mechanism for removing unwanted substances from the plasma. Substancessuch as H

    +, K

    +, creatine, NH4

    +, and certain organic acids move from the blood of the peritubular

    capillaries through the tubule cells, or from the tubule cells themselves into the filtrate. With theexception of K+(which is mainly secreted from the distal tubule and collecting duct), theproximal tubule is the main site of secretion. Tubular secretion is essential for:

    o Removal of substances not already in the filtrate, such as certain drugs;o Removing unwanted substances or metabolic waste products such as urea and uric acid,

    which have been reabsorbed by passive processes;

    o Removal of excessive K+; and

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    o Controlling blood pH.If blood becomes acidic, the renal tubule cells actively secrete H

    +into the filtrate and retain more

    HCO3-, and K

    +. By contrast, if blood becomes alkaline, Cl

    -is reabsorbed and more HCO3

    -leaves

    the body in the urine.