Excretion and homeostasis

Fox Chapter 17, one figure from Chapter 6

How the kidneys function is way more interesting than you may have thought. Summarizing, they throw the baby out with the bath water, then recover most of it.

Consider the work of the kidneys

Artificial kidney (dialysis) 10 hr 2 times per week
This is why transplant important, and there is difficulty getting a compatable donor.
Cell makes wastes that go into the plasma.
Heart pumps 7000 l/day (32 55 gal drums).
1/4 (8 55 gal drums) through kidneys
Glomerulus - Bowman's capsule passes (filters) 180 l/day.
And yet only 1 l of urine is produced per day.

Osmoregulation (for ions)

Review:
Hypertonic (concentrated), isotonic, hypotonic (dilute).
Nitrogenous waste (urea) is from catabolism of amino acids and nucleotides.
Ammonia (toxic) would be o.k. for small water animals where it can diffuse away.

Comparative biology

There is a tradition in undergraduate biology to emphasize comparative aspects:
Malpighian tubule in insects puts out uric acid and rectum recovers water and other molecules.
Uric acid is used in birds, reptiles, and insects, and water loss is minimized

The nitrogen story

Although 78% of the atmosphere is nitrogen in the form of N2, this is fairly unreactive.
Thus there are these important processes: N2 to NH3 nitrogen fixation, NH3 to NO3- (nitrate) nitrification, NO3 to NH3 (nitrate reduction) in plant roots.
Also nitrogen is recycled.
In Pacific, off the coast of Peru, the Humbolt current causes an upwelling of nutrients, anchovies thrive, bird droppings (guano) were used as fertilizer.
El Nino (the Child, named not for misbehavior but because it comes near Christmas) is a periodic climate misbehavior that disrupts this.

The uric acid story

In humans, mild accumulation of uric acid causes gout - crystals in joint cause inflammatory response which is treated by NSAIDS (non-steroidal anti-inflammatory drugs like prostaglandin inhibitors like indomethacin, ibuprophin, and aspirin). Enzyme is inhibited by chronic treatment with allopurinol. Genetically pathological uric acid accumulation which is Lesch-Nyhan syndome - children have bizarre self mutilation from HGPRTase (hypoxanthine guanine phospho ribosyl transferase) deficiency.

Functional anatomy

Fig. 17.1
kidney, ureter, bladder, urethra

Fig. 17.2
Kidney
Pelvis=basin; Medulla=marrow; Cortex=bark ("medulla" and "cortex" are terms used a lot, like in brain and in adrenal gland)
The blood supply is huge (1/4-15 of body at rest) and regulated (way less in stress)
Renal artery and vein branches near eachother
each kidney has 1 million nephrons:
Capsule, PCT, loop of Henle, DCT, collecting duct (this will be repeated in other figures)

Filtration

Fig. 17.5
Blood flow in glomeruli
Notice "afferent" (toward) and "efferent" (away from) arterioles, implies a portal system to next capillary bed iaround nephron and in medulla

Fig. 17.13
Glomerulus - Bowman's (glomerular) capsule
I picked just one figure, when the book uses several to develop the point gradually.
Blood pressure and osmotic pressure drives sieve
Green is protein that is too big to fit through.
Blue is all small molecules.
Na+ is actively transported, Cl- and H2O follow

Fig. 17.7
Fig. 17.9
Glomerulus - fenestrae (windows) in capillaries and slits between podocyte pedicels make up sieve.
here is a picture from the histology course
another picture highlights glomerulus by dye injected into artery
large molecules dye do not pass
- small molecules dye passes through
blood proteins and cells do not pass
urinalysis strips test if blood, cells or protein is present

Clearance test for filtration

Fig. 17.22
One test of kidney function, specifically filtration, is inulin clearance test
Inulin is an injected dye that is filtered but not resorbed.
Short of injecting inulin, an endogenous molecule, creatinine, can be assayed.

Resorption of glucose

Fig. 17.24
Proximal Convvoluted tubule - bring back amino acids, glucose note active (NaCl) vs passive (water) transport
Glucose is a special case.
(1) ATP is used in a Na+-K+ pump on basolateral cell surface
(2) glucose is cotransported with Na+ on apical cell surface
(3) Cells are joined so there are no other pathways
(4) recovery in capillary is by diffusion
Why an untreated diabetic has glucose in the urine is that this mechanism is saturated and cannot recover all of the glucose filtered from high blood glucose.

Resorption of salt

Kangaroo rat - metabolic water, hypertonic urine

Fig. 17.14
Ascending loop - salt resorbed but not water
Ascending loop of Henle - salt outward resorption is stimulated by aldosterone
Some passive water recovery is made possible because of high tonicity of interstitial fluid in the medulla.
This is called the countercurrant system

Fig. 17.18
A summary shows dilute in cortex, hypertonic in medulla

Secretion

Fig. 17.21
Kidney also secretes - pump out (penicillin)

Hormonal control

TRANSPARENCY (from an intro book)
ADH (vasopressin) makes water follow back into interstitial fluid which is hypertonic from salt
alcohol and caffeine inhibit ADH, hence diuresis (excessive urination)
affects water channels called aquaporins

Fig. 17.20
regulation of ADH by negative feedback (from hypothalamus to pituitary) and relation to thirst and water intake

Fig. 6.14
This same concept was covered way back in Chapter 6.
The relation of thirst to water conservation via ADH

Fig. 17.26
low blood pressure -> JGA (juxtaglomerular apparatus) makes renin

Fig. 17.27
Renin causes Angiotensinogen (liver) -> angiotensin II- closes arterioles
stimulates aldosterone

High blood pressure ->atrial natriuretic protein ->(-) aldosterone and renin

Sweat

Filter, resorb (salt and water)
Sweat pores not as good -which is why gatorade tastes good to athletes
especially bad in cystic fibrosis (salty sweat) molecular genetics shows a chloride channel defect

Exam questions from 2004 - 2011 relating to this outline

Uric acid: Answer either (1) Why would you take NSAIDS (non-steroidal anti-inflammatory drugs) if your uric acid were high? or (2) Why would you dig up uric acid from the islands off the coast of Peru?

reduce inflammation in a gout attack, for nitrogen fertilizer

In the glomerulus, fluid passes through the fenestrated capillary endothelium plus (what?) on its way to Bowman's capsule.

pedicels of podocytes

Aldosterone. Answer one of the following: (1) Where specifically is it from? (2) Where (specifically) does it act? (3) What would happen to an animal who has no aldosterone?

zona glomerulosa in adrenal cortex, ascending loop of Henle, would lose salt in the urine and crave salt

Angiotensin is activated in a low blood crisis; another hormone regulates angiotensin activation. Answer either (1) Where is this other hormone secreted from? or (2) What is this other hormone called?

JGA in kidney, renin

Why would it be advantageous for some animals to use uric acid instead of urea to eliminate nitrogenous wastes?

less water is lost

Where does the efferent arteriole from the glomerulus go to next?

vasa recta, capillary bed around loop of Henle

Where (answer either cellular location or molecule) is energy used to resorb glucose across a cell in the kidney tubule?

basolateral surface, sodium pump

ADH (antiduretic hormone, alias vasopressin). Answer (1) What channels are regulated by ADH? or (2) Where (specifically) does ADH have its effects?

water channels (aquaporins), collecting duct

Why is it advantageous for some animals to use uric acid rather than urea in their excretory systems?

less water is lost

26. "Upwelling of nutrients off the coast of Peru." Answer either (1) What ocean current helps with this? Or (2) What is the climate abnormality that disrupts current and upwelling?

Humboldt current, El Nino

27. Non-steroidal anti-inflammatory drugs (NSAIDS) inhibit the formation of what mediator of inflammation?

prostaglandins

Peritubular capillaries (the vasa recta) form part of the kidney's portal system. Where is the other capillary bed?

the glomerulus

A basement lamina separates two components of the glomerular sieve. Name one of these two cellular components.

podocyte's foot processes and fenestrated capillary

Facilitated diffusion for glucose takes place on the basolateral surface of a proximal tubule cell. For EITHER of the other two essential components of glucose transport in this cell type, give BOTH the membrane transporter PLUS the location of the membrane.

cotransport-apical, sodium pump-basolateral

What function does it serve to have salt but not water transport in the ascending limb from the loop of Henle?

to increase the osmolarity of the interstitial fluid

Elimination of what hormone from your body would make you crave salt?

aldosterone

ACE=angiotensin converting enzyme: Answer EITHER (1) What hormone from the kidney activates ACE? Or (2) For what disorder might you want to inhibit ACE?

renin, hypertension

People with gout have high levels of what substance?
 
Uric acid
 
Many people enjoy an electrolyte replacement beverage such as Gatorade if they perspire a lot. They do not like such drinks if they pee a lot. Why the difference?
 
More salt is lost in sweat than in urine
 
For ADH (antidiuretic hormone = vasopressin), answer one of these (1) What does it do to the membrane to facilitate transport? Or (2) Where, in the kidney, does it have its effect?
 
Adds aquaporins (water channels) in the collecting duct
 
Blood arrives at the glomerulus for filtration. What do they call the blood vessel that carries blood away from the glomerulus?

efferent arteriole

In addition to facilitated diffusion at the basolateral cell surface, what is necessary for glucose transport in kidney tubule and intestinal cell? (Include process and location.)

apical cotransport with Na+

What is the product of the juxtaglomerular apparatus?

renin

High levels of what nitrogen-containing chemical cause gout?

uric acid

Why are alcoholic beverages contraindicated to stay hydrated in times of heat stress? (Make sure your answer says what happens to the relevant hormone level.)

alcohol inhibits ADH, more water is lost through kidney

Cystic fibrosis is a channel for what ion?

Cl-

Where are the cell bodies of the cells whose axon terminals release ADH and oxytocin?

hypothalamus

What does creatinine clearance test for?

glomerular filtration

In the intestine and the kidney tubule, three processes are needed for glucose transport, (1) basolateral sodium pump, (2) basolateral facilitated diffusion, and (3) apical... [your
turn].

glucose/sodium cotransporter

Because of the portal system, the vessel carrying blood from the glomerulus is not called a vein. What is it called instead?

efferent arteriole

If a kidney stone passed from the kidney to the bladder, what tube would it go through?

ureter

What accumulates in Lesch-Nyhan syndrome?

uric acid

By what mechanism are proteins excluded from the primary filtrate in the kidney?

size of sieve openings (podocytes and fenestrated endothelium

Why might you give a secretion blocker in conjunction with penicilin?

keep antibiotic from being pumped out by kidney

Why do cells in the proximal convoluted tubule need to pump sodium to reclaim glucose?

because of sodium-glucose cotransporter ion apical surface

In what tube does the final, ADH-dependent, water reclamation occur?

collecting duct

Instead of injecting inulin, what test is there for clearance assaying for a substance already in the body?

creatinine

Renin activates what hormone?

angiotensin II

In the kidney tubules, salt and water are reclaimed. Only one substance is actively transported. What substance? (Be specific.)

sodium

What hormone from the adrenal cortex is essential for salvaging salt in the kidney?

aldosterone

There is a capillary bed in the glomerulus. Where is the other capillary bed of this portal system?

medulla

Na+, Cl- and H2O are all recovered in the proximal convoluted tubule. Which involve active transport?

Na+

Aquaporins in the collecting ducts are regulated hormonally. What are aquaporins?

ater channels

At what location in the lumen of the kidney tubules is the tonicity the highest?

loop of Henle (and maybe deep collecting duct)

Describe either how the kidney deals with inulin or, alternatively, what specific aspect of kidney function inulin is used to test.

filters but does not retrieve, tests GFR=glomerular filtration rate

Considering how unreactive nitrogen gas (N2) is, how did it get into biological molecules such as amino acids?

nitrogen fixation

The glomeruli vs. the loops of Henle are in which two overall anatomical portions of the kidney respectively?

cortex, medulla

In addition to the fenestrations in capillaries, what cellular architecture is responsible for glomerular filtration?

pedicels of podocytes

What change in appetite would occur if the adrenal glands were removed?

you would crave salt

What is detected by the juxtaglomerular apparatus that makes these granular cells release their renin?

pressure in afferent arteriole

If you drink very little and become thirsty, what pituitary hormone would be increased?

ADH=antidiuretic hormone

What are creatinine and inulin reapectively and what are they used for?

creatinine is already in body and inulin is injected, buth used to test glomerular filtration since they are filtered but not resorbed

For glucose in the kidney, tell me the surface locations of the three transporters involved.

cotransport apical, basolateral facilitated diffusion plus sodium pump

What should happen to the tonicity of urine if a drug that inhibits ADH (antidiuretic hormone) were administered?

becomes dilute

Why are drugs like aspirin called prostaglandin inhibitors?

they block synthesis by blocking the cyclooxygenase (COX)

What is the tube that connects the kidney with the bladder?

ureter

What do they call the blood vessel exiting the capillary bed that is in the glomerulus?

efferent arteriole

Salt and water are recovered in the proximal convoluted tubule. What is active and what is passive? Be specific.

sodium ion active, chloride and water passive

Why would a rat drink salty water after an adrenalectomy?

aldosterone which favors salt recovery would be missing

Where, in the nephron's components, are the aquaporins that are influenced by ADH (antidiuretic hormone)?

collecting ducts

What does the juxtaglomerular apparatus monitor and why is it in a good location to do this job?

blood pressure, near afferent arteriole

From the renal pelvis, the urine flows to the bladder via what tube?

ureter

Why is it advantageous to have hypertonic interstitial fluid in the kidney medulla?

Then, if ADH is present, water will be salvaged from the collecting duct

Why would it be advantageous to position renin secreting cells where they are?

Blood pressure is monitored near the glomerulus for the emergency work of angiotensin that rennin initiates

Drugs that inhibit prostaglandin synthesis might help with the symptoms of gout. Why?

b/c it is the inflammatory response to the uric acid in the joint that is pain

What is wrong in Lesch-Nyhan syndrome children (HGPRTase deficiency)? (Your answer can be behavioral or chemical.)

self-mutilation, uric acid accumulation

What blood vessel connects the two capillary beds of the nephron and hence serves as the portal vessel?

the "arteriole" that is efferent from the glomerulus

Out of all the things a nephron does, inulin clearance tests for just one. What?

glomerular filtration

How is glucose transported at the apical surface of the cell of the kidney tubule?

apical is the co-transport with Na+

What would an adrenalectomy do a rat's specific appetites?

without aldosterone, there would be increased sodium appetite

What would inhibiting ADH do to the urine?

inhibiting antidiuresis, two negatives make a positive, so diuresis, more (and more dilute) urine

How and where does ATP get used for glucose resorption in the kidney?

sodium pump on basolateral surface in proximal tubule

How do water and salt transport differ in the proximal convoluted tubule vs. the ascending limb from the loop of Henle.

in both cases, sodium transport is active. Water follows in the PCT but not in the ascending limb

By what molecular mechanism would ADH (antidiuretic hormone) make the collecting duct recover water better?

add aquaporins

In describing the work of the kidneys, some relevant volumes were graphically described in terms of drums containing 55 gallons. Why were there 32 and 8 drums in that story?

32 volume of blood pumped daily, 8 through kidneys

"A disruption in the Humboldt current might have an effect on bird droppings." Fill in a few of the details missing in that telegraphic statement.

bird droppings - uric acid, nitrogen fertilizer, birds eat anchovies which thrive b/c of Humboldt driving upwelling

In the portal system of blood flow in the kidney, describe the anatomical localization of the second capillary bed (vasa recta).

surrounds each loop of Henle in medulla

In addition to foot processes (pedicels) of podocytes, how else is a fine-mesh mechanical sieve achieved in the glomerulus?

fenestrated endothelium

Why would an adrenalectomy cause an animal to have a specific appetite for salt?

loss of aldosterone makes kidneys lose salt

What change of appetitive behavior would accompany an increased secretion of ADH (antidiuretic hormone)?

while kidneys wold conserve water, you would also be thirsty

For hormonal control originating from the juxtaglomerular apparatus, answer either (1) What purpose does it serve? Or (2) Why is the location of the juxtaglomerular apparatus ideal for monitoring this need?

emergency response to low blood pressure, near afferent arterioles



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