Excretion - MR. GALLANT'S CLASSES · Excretion 6/4/08 Human Biology 1 Excretion A. Excretion Notes 1. Definitions • Excretion - release of metabolic wastes and excess water •

Excretion 6/4/08

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 urea

c. Large Intestines

- excretes Calcium and Iron salts - defecation

d. Kidney - ammonia, a toxic by-product of metabolism of

proteins is converted to urea in the liver, which is excreted here

- hypothalamus regulates function with hormones

- ADH raises the osmotic concentration within kidney, and so promotes the reabsorption of water

- Aldosterone stimulates sodium ion reabsorption e. Lungs

- CO2, and water

3. Key Definitions a. Kidney

- the organ the filters the blood (600 L/day) to remove nitrogenous wastes and regulates the balance of water and solutes in the blood plasma. - Cortex

Text Diagram: Kidney

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

and o Bile is secreted and/or

excreted depending on your point of view.

Intake of water o Drink 1500ml/day o Food 1000ml/day o Metabolism 200-350ml/day

Excretion of water

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

Erythropoietin The kidneys make this hormone, which stimulates the bone (red) marrow to make blood cells, in response to low levels of O2 in the blood.

Excretion


- 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 the bladder

c. Bladder

- stores urine, prior to elimination

d. Urethra - the tube carrying urine from the bladder to the exterior

of the body

Excretion


4. The Nephron

- the functional unit of the kidney; one of numerous tubules (about a million) involved in filtration and selective reabsorption of blood. Each one consists of a Bowman’s capsule, an enclosed glomerulus, and a renal tubule

Arterioles - Afferent arteriole

Text Diagram: Nephron

Adrenal Gland - Adrenalin – medulla - Aldosterone - cortex

Excretion


- 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 Renal vein

- helps maintain concentration gradient in the medulla for reabsorption

Glomerulus (L. “little ball”)

- a cluster of capillaries enclosed by the Bowman’s capsule.

Bowman’s Capsule

- the bulbous unit of the nephron, which surrounds the glomerulus. The kidney works by forced filtration, blood pressure driving blood plasma from the glomerular capillaries into the Bowman’s capsule, after which it passes through the nephron, 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 the glomerular capillaries into the Bowman’s capsule, through which it enters the renal tubule; the filtrate contains water and ions (which are recovered) and metabolic 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) Reabsorption o 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 DCT

and the afferent arteriole

- note the variation in this

diagram…it is actually a more realistic image than the splayed open image generally used to label the parts on the provincial exam, and seen on the previous page.

Excretion


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

o Cations: Creatinine Quinine, Dopamine, Adrenaline /

Epinephrine Isoproterenol - Aldosterone, increased reabsorbtion of Na+ (excretion

of K+) and water along the ascending limb and arch) Collecting Duct (CD, CT)

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

- Aldosterone, increased permeability to “salt” (Na+),

results in increased “salt” (Na+) reabsorption o Side affect increased reabsorption of water o Increased excretion of K+ in urine o 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 of water from the filtrate out into surrounding tissue, where it is collected by blood vessels impermeable to the high urea concentration but permeable to water.

- as such human urine may be as much as 4.2 times as

concentrated 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 a

countercurrent flow. The longer the loop the greater the water reabsorption. The countercurrent processes involves 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 by active transport occurs

Tubular Secretion This is an essential mechanism for removing unwanted substances from the plasma. Substances such 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. 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 o Controlling blood pH.

If blood becomes acidic, the renal tubule cells actively secrete H+ (at DCT) into the filtrate and retain more HCO3

- (at PCT), and K+. By contrast, if blood becomes alkaline, Cl- is reabsorbed and more HCO3

- leaves the body in the urine.

Excretion


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 the

process. 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 bottom of 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.)

- Ammonia is toxic to all cells, therefore it must be

removed 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 ammonia by

converting it to urea in the liver which is far less toxic, and can be transported at far higher concentrations

- the urea is carried by the blood stream to the kidneys, where it is excreted as the principal component 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

Excretion


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 nervous

system - voluntary, autonomic, and hormonal controls

- the body requires that the osmotic concentration of

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 the production of Aldosterone

a. Water Balance (Osmoregulation)

- Antidiuretic hormone (ADH) aka vasopressin regulates the volume of water excreted by the kidneys.

- ADH increases the permeability of the distal convoluted tubule and the collecting duct to water.

- ADH is produced in hypothalamus and descends along nerve fibres to the posterior pituitary, where it is stored for subsequent

- release

- Its secretion is regulated by the osmolality of the body fluids and the blood volume and pressure.

- Changes in body fluid osmolality of a few percent are sufficient to significantly alter ADH secretion.

Review: What is Albumin? - made in the liver, a key plasma

protein responsible for maintaining the osmotic pressure in the blood.

- cf. Digestive system notes

Hormones: - Antidiuretic Hormone (ADH)

which stimulates passive water reabsorption

- Aldosterone which stimulates active sodium reabsorption…

Excretion


- Decreases in blood volume and pressure of 10% to 15% or more are needed to effect ADH secretion.

- The blood volume and pressure sensors are found in the large pulmonary vessels, the carotid sinus, and the aortic arch. These “baroreceptors” (stretch receptors) respond to stretch of the vessel wall, which in turn is dependent on blood volume and pressure.

If Too Much Water: - osmoreceptors in the hypothalamus detect the

decrease 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 increased reabsorption of water…signaling a decrease in ADH production

If Too Little Water:

- ADH release is increased - by high blood osmolality affecting

hypothalamic osmoreceptors and - by low blood volume affecting the

baroreceptors/stretch receptors; - low osmolality and high blood volume

inhibit ADH release

- ADH causes walls of collecting ducts to become more permeable to water and thus permits osmolar equilibration and absorption of water into the hypertonic medulla;

- a small volume of highly concentrated (hypertonic) urine is excreted

ADH makes the walls of the DCT and collecting tubule more permeable to water so that more water will be reabsorbed and less will be excreted with urine. Alcohol inhibits ADH, decreasing the reabsorption of water, and filling the bladder faster, resulting in… Diuresis, the increased production of urine by the kidney…leading to increased micturition / voiding / urination — aka #1 or peeing.

Osmolality: - measure of the solute

concentration. High osmolality means more solute, and less solvent (water). Low osmolality means less solute, and more solvent (water).

So why is the medulla hypertonic? ∵ of aldosterone (see notes below)

- DCT and CD are made permeable to Na+ which flood the medulla…

Excretion


Source: VPL Science Librarian b. Salt Balance

- for various reasons the salt levels in your blood must not vary widely; although intake may vary

- when sodium ion levels drop in association with low blood volume (low blood pressure), the hormone Renin stimulates the adrenal cortex increases production of aldosterone

- a steroid hormone that stimulates active

sodium (and water) reabsorption - via the:

- DCT (ascending limb and arch) and CD

- Juxtaglomerular apparatus – contact between the afferent arteriole and DCT

- when blood volume (and blood P) drops, - detected by “stretch receptors”

Aldosterone causes 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 at

the PCT, DCT and CD - Na+ is passivley reabsorbed at

the ascending loop of Henle

Excretion


(osmorecepotors) in the Juxtaglomerular apparatus — i.e., reduced stretch of Juxtaglomerular cells

- and glomerular (pressure) filtration decreases the Juxtaglomerular apparatus secretes Renin

- Renin

- (changes angiotensinogen [a plasma protein from the liver] into angiotensin I which then becomes angiotensin II, a vasocontrictor that also)

- stimulates the adrenal cortex to secrete aldosterone

- “The reabsorption of Na+ is followed by the reabsorption of water. Therefore, blood volume and blood pressure increase.”

- Byproduct is the co-transport of Cl-, HCO3-, H+, and

K+ (although, generally K+ are more likely to flowing

in the opposite direction, excreted with the urine because of aldosterone).

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

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

- Because of the (hypertonic) concentration gradient set

up by aldosterone, water, will also be reabsorbed (cf. ADH)

Source: VPL Science Libarian

- Aside: - ANH (Atrial Natriuretic Hormone)

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

increased blood volume

Filtered Load Factors That Stimulate

Factors That Inhibit

Reabsorbed (%)

Reabsorption Reabsorption

Proximal tubule

67 Angiotensin II Sympathetic nerves Dopamine

Loop of Henle 25 Sympathetic nerves Distal tubule ~4 Aldosterone Collecting duct

~3 Aldosterone Atrial natriuretic peptide (ANP)

The kidney is also responsible for activating vitamin D3. A critical anti-cancer vitamin. Vitamin D (cholecalciferol) can either be ingested with food or made from 7-dehdrocholesterol by the action of ultraviolet light (sit out in the sun and make vitamin D). The liver converts cholecalciferol into 25-hydroxycholecalciferol and the proximal tubule cells of the kidney convert 25-hydroxycholecalciferol into 1,25-dihydroxycholecalciferol. This is the active form of vitamin D3. Vitamin D is very important to dentists because (along with parathyroid hormone, PTH and calcitonin) it controls many aspects of calcium metabolism in the whole body. (Do not confuse regulation of calcium metabolism by vitamin D etc. with the role of calcium as an intracellular second messenger. There are indeed overlaps between these processes, but tread carefully.) Vitamin D is involved in stimulating the absorption of calcium from the diet, in laying down of calcium into the bone and, most importantly (at least from the point of view of a dentist) in the mineralisation processes involved in dentinogenesis and amelogenesis. If you don't have enough vitamin D as a child you get rickets (bendy bones) and bad teeth. The traditional illustration of this is in Victorian child mineworkers who rarely saw the sun (and probably had a poor diet as well).

- source: Pete Smith (http://www.liv.ac.uk/~petesmif/teaching

/1bds_mb/notes/kidney/endocrn.htm)

Excretion


Source: VPL Science Librarian

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

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

Renin-Angiotensin-Aldosterone System

Excretion


+ efferent arterioles peritubular capillaries (venule) ultimately to the Renal Vein + below the Inner medulla feeding the Ureter is the Renal Pelvis

Glomerular Filtration Tubular Reabsorption Tubular Secretion (Excretion)

Ammonia, uric acid, H+, penicillin, creatine

Excretion


Key Hormones (Simplified) Hormone Summary

Source - Hypothalamus, but stored and released from the posterior pituitary gland

Stimulus - Secretion in response to reduced plasma volume is activated by pressure receptors in the veins, atria, and carotids. (too little water)

- Secretion in response to increases in plasma osmotic pressure is mediated 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 cortex Stimulus - Presence of Renin (due to sodium deficiency);

- Decreased BP (as detected by stretch receptors in the atria of the heart)

Aldosterone

Function - reabsorbs Na+, (and indirectly water) - excretes K+, - raises blood pressure

Source - juxtaglomerular apparatus (between glomerulus and DCT)

Stimulus - Low blood volume - Decreased “salt” (NaCl)

Renin

Function Renin activates the renin-angiotensin system by cleaving angiotensinogen, 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 directly

related to the excretory system. What gets Reabsorbed & Where Tubule Segment Substance Reabsorbed Mechanism

Na+ Active transport Virtually all nutrients (glucose,, a.a. , vitamins…)

Active transport (cotransport with Na+)

Anions (Cl-, HCO3-)

Passive transport (cotransport with Na+ for HCO3- by active transport)

Cations (K+, Mg2+, Ca2+…) Passive transport Water Osmosis Urea and lipid-soluble solutes

Passive diffusion (side effect of gradient created by movement of water)

PCT - Tubular Reabsorption - Selective Reabsorption

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

Excretion


Loop of Henle Descending Loop

Water

Osmosis

Salt (Na+, Cl-) Passive transport Salt (Na+, K+, Cl-) Active transport

Ascending Loop

Ca2+, Mg2+ Passive transport Na+ Active transport (Aldosterone) Ca2+ Active transport (PTH) Cl-

Diffusion, some co-transport w/ Na+ (active)

DCT

Water Osmosis (ADH) Na+, Active transport (Aldosterone) Cl-, HCO3-

Passive transport (side effect of gradient created by aldosterone)

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

Collecting Duct

Urea Facilitated diffusion (most remains 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 = ~0 Na+ 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

Excretion


Summary of Nephron Function

Source: Human Anatomy and Physiology 6ed., E. N. Marieb Summary Source: 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 of blood. It does. The kidney receives 25% of cardiac output, which is about 1200 ml/min or over 1700 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 99.4 Potassium 600 50 90 560 93.3 Chloride 18,000 150 17,850 99.2 Bicarbonate 4,900 0 4,900 100 Urea 870 410 460 53 Glucose 800 0 800 100 Total solute 54,000 100 700 53,400 87

Excretion


(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 Processes Source: http://www.bioeng.auckland.ac.nz/physiome/ontologies/urinary/tissues.php Glomerular Filtration Is a passive, non-selective process, where fluids and solutes are driven through a membrane under 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 the renal tubule. Tubular Reabsorption Of the ~125 ml of plasma filtered by the glomeruli, 124 ml is reabsorbed during passage through the renal tubules. Tubular reabsorption is a transepithelial process carried out in the PT, loop of Henle, DCT and the collecting ducts. Water, ions and nutrients are reabsorbed either passively along their electrochemical gradients, by simple diffusion, facilitated diffusion, and osmosis, or they are actively reabsorbed via cotransporters. Cotransporters often couple the free energy released by the energetically favourable movement of Na+ along its electrochemical gradient to the transport of substances such as amino acids and glucose against their electrochemical gradients. To some degree, the entire length of the renal tubule is involved in reabsorption, however, the cells 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. The proximal tubule is the site of most reabsorption. Tubular Secretion This is an essential mechanism for removing unwanted substances from the plasma. Substances such 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 the exception of K+ (which is mainly secreted from the distal tubule and collecting duct), the proximal 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

Excretion


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.

Excretion - MR. GALLANT'S CLASSES · Excretion 6/4/08 Human Biology 1 Excretion A. Excretion Notes 1. Definitions • Excretion - release of metabolic wastes and excess water •

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