Communication and Homeostasis pt2 Kidneys and Liver Flashcards
what is excretion
removal of metabolic waste from cells of body.
The removal of by-products or unwanted substances from normal cellular processes to maintain homeostasis
what is the formula of urea
what is the amine group
what is the rest know as and what is it used for
CO(NH2)2
NH2 is the amine group
the rest is the keto group which is involved in respiration
what happens to the amine group of excess amino acids
- what and where does it take place
- what does it form
removed in excretion by deamination which takes place in the liver.
amine group joined with hydrogen to form ammonia NH3 and then into urea
Why must ammonia be converted to urea
because ammonia is a highly soluble highly toxic substance.
what happens to the urea
dissolved in water in the blood and is filtered in kidneys through ultrafiltration and expelled in urine
what is the ornithine cycle
- cycle where amine group is metabolised in liver into ammonia
what are the differences between excretion and secretion
excretion is…..
- metabolic waste such as CO2 urea and water
- not packaged in vesicles
- substance removal from body
secretion is….
- useful products such as hormones eg insulin
- packaged into vesicles
- excocytosis
why do fish excrete ammonia but mammals must convert it to urea for excretion
- fish are surrounded by water in an aquatic environment so ammonia is kept as dissolved in water so is just expelled
- terrestrial mammals aren’t surrounded by water so ammonia is not dissolved in as much water to be safe so must be converted to urea to less toxic and less soluble
difference between excretion and egestion
excretion is removal of metabolic waste out of body from cells
whereas egestion is removal of indigestible material
what is deamination
process where urea is made from excess amino acids
why are excess proteins removed
body can’t store excess proteins but removing all amino acids would be wasteful as they contain energy
(so those that arent immediately needed are deaminated in liver)
how is ammonia formed
deamination of amino acids removing the amino group together with a hydrogen atom to form ammonia (nitrogenous product)
why must ammonia be converted to urea
soluble but highly toxic substance so must be converted to stop build up in blood+ immense damage
urea is less toxic and less soluble
chemical equation for formation of urea
2NH3 + CO2»_space;»> C(NH2)20+H20
where are the kidneys found
back of abdominal cavity
what surround the kidneys
thick layer of protective fat called adipose tissue and fibrous connective tissue
how are kidneys involved in osmoregulation
as well as filtering nitrogenous waste the kidneys maintain water balance and pH of blood
what supplies the kidneys with blood
oxygenated blood from renal arteries which branch from abdominal aorta at arterial pressure
where is deoxygenated blood removed from kidney
removed from renal vein that drains into inferior vena cava
about 90-120cm^3 blood passes through kidney every minute
what parts make up the kidney
cortex
medulla
pelvis
what does the cortex of the kidney do
outer layer
-where filtering takes place, very dense capillary network carrying blood from renal artery to nephrons
what is the function of the medulla of the kidney
contains tubules of nephrons that form pyramids of kidney and also the collecting ducts
appears lighter on micrographs
what is the function of the pelvis
(basin) central chamber urine collects in before going to urteter
where is blood filtered in kidney and what are they removing
the nephrons
- nitrogenous waste (urea)
- excess water
- excess ions
about 3cm long and there are 1.5 million in each of the kidneys
why are there so many nephrons
-provides body with several km of tubules for reabsorbtion of water glucose +salts ect. (large SA:V)
STRUCTURE OF NEPHRON
what is the bowmans capsule
-what does it look like and contain?
- cup shaped feature
- contains glomerulus and a tangle of capillaries
- more blood goes into glomerulus than leaves due to ultrafiltration
STRUCTURE OF NEPHRON
what is the proximal convoluted tubule
- first coiled region of tubule after the bowmans capsule
- found in cortex where many substances needed by body are reabsorbed into blood
LOOK UP DIAGRAM OF STRUCTURE OF KIDNEY
I HOPE YOUVE DONE IT :)
STRUCTURE OF NEPHRON
what is the loop of Henle
where do descending and ascending limb go
long loop of tubule that creates a region w/ high, very solute concentration in tissue fluid deep in kidney medulla
- the descending loop runs down cortex through medulla to a hairpin bend at the bottom of loop
- ascending limb goes back up through medulla to cortex
STRUCTURE OF NEPHRON
what is the distal convoluted tubule
-what occurs here
-how does permeability of walls change
a second twisted tubule where the fine tuning of water takes place
- permeability of walls to water varies in response to levels of ADH (antidiuretic hormone) in blood
- further regulation of ion balance+pH of blood takes place here too
STRUCTURE OF NEPHRON
what is the collecting duct
- urine passes down collecting duct through medulla to pelvis.
- More of the fine tuning of water balance takes place here
- walls of tubule are sensitive to ADH
what do the network of capillaries around nephron lead to
venule»»> vein
characteristics of blood leaving the nephron
- no urea
- levels of glucose and other substances such as amino acids needed by body stay pretty much same! some glucose is used in selective reabsorption tho
- mineral ion concentrations restored to ideal level.
why does the efferent arteriole have a narrower lumen than the afferent arteriole
it creates a higher pressure to push substances out of capillaries into surrounding area for ultrafiltration.
what is the purpose microvilli in the nephron
increase SA for selective reabsorption
why are the convoluted tubules wiggly
to increase SA
where does the capillary bed of the nephron drain back to?
the renal venule
what is the glomerular filtrate
- around lumen surrounding glomerulus
- The fluid in the lumen of the Bowman’s capsule of the nephron that has been filtered from the capillaries of the glomerulus
what is the first stage of the removal of nitrogenous waste and osmoregulation of blood called?
Ultrafiltration
where does ultrafiltration occur
what does it form
in the kidney tubules in the bowmans capsule
-results in formation of tissue fluid in the capillary bed of body
its resulted of the structure of glomerulus and cells lining the bowmans capsule
where does glomelulus gets blood from
a relatively wide arteriole from renal artery (afferent arteriole)
where does blood leave the glomerulus
by narrower efferent arteriole due to pressure in capillaries of glomerulus
this forces blood out of capillary wall through the basement membrane
what is the basement membrane and what is it made of
important in filtration process
-made of network of collegen fibres and proteins making a 2nd sieve
what can’t go through the basement membrane
blood cells and many proteins left in capillary as too big to leave
what is the name of the specialised cells in the bowmans capsule
podocytes- they act as an additional filter
what adaptations do podocytes have
extensions called pedicels that wrap around capillaries which forms slits
these make sure any cells, large plasma proteins or platelets that have managed to get through epithelial cells and basement membrane dont get through the tubule itself
what does the filtrate entering the bowmans capsule contain
glucose salt urea blood plasma
what is the glomerular rate
volume of blood filtered through kidneys at given time
why do some substances need to be reabsorbed in nephron and give examples
needed by body
|»_space;> eg glucose for respiration so isnt excreted (unless diabetic)
ultrafiltrate is _____ to the blood plasma concentration
hypotonic (less concentrated)
what is the main function of the nephron
to return most filtered substances back to the blood
what is reabsorbed back into the blood
all amino acids, vitamins, glucose and hormones and 85% of salts and water
how do sodium ions move out of proximal convoluted tubule
active transport
how do Cl- ions and water leave proximal convoluted tubule
passively down a concentration gradient by osmosis/ diffusion
describe the characteristics of the cells in the proximal convoluted tubule
- covered with microvilli- greatly increases surface area so substance can’t be reabsorbed
- many mitochondria- to provide ATP needed for active transport systems
- basement membrane which goes to lumen of blood capillary which is one endothelial cell thick
when substances have been removed from nephron where do they go?
how is the gradient maintained
they diffuse into capillary network surrounding the tubules down a concentration gradient which is maintained by constant flow of blood through capillaries
filtrate reaching loop of henle at the Promixmal convolued tubule end of the capillary is ______ to the tissue fluid surrounding the tubule and the blood
isotonic
at this point 80% of glomerular filtrate reabsorbed into blood
what is the function of the loop of henle
enables the mammals to produce urine more concentrated than their own blood
how does permeability change in the loop of henle
different areas are more permeable to water (lower part)
loop of henle acts as a C_____ M______ which means that it:
Countercurrent Multiplier
uses energy to produce a concentration gradient which results in the movement of water and other substances from one area to another
Uses ATP to transport ions by active transport and produces a concentration gradient in the medulla in the ascending limb
describe the permeability of the upper part of the descending limb of the loop of henle
-upper part impermeable to water
describe the permeability of the lower part of the descending limb of the loop of henle
permeable to water (this section is in the medulla not cortex of kidney)
how does the concentration of sodium ion concentration in tissue fluid of medulla change as they move through from cortex to the pyramids
what is the due to?
increases
due to activity of ascending limb of loop of henle
filtrate entering the the descending limb of the loop of henle is ______ to the blood
isotonic
how does water leave descending limb of loop of henle and where does it go
- passes out into tissue fluid by osmosis
- down a concentration into the surrouding capillaries
(the vasa recta)
the descending limb of the loop of henle is _____ to sodium and chloride ions
not permeable
no active transport takes place
describe the water potential at the bottom of the loop of henle
therefore describe the fluid at the hairpin bend of the loop
very low
highest at top of ascending loop and also high at descending loop
fluid is very concentrated and will be hypertonic to blood in capillaries
which section of the loop of henle is very permeable to sodium and chloride ions
how does the differ in the second part of that section
what does this result in, in the medulla
the first section of the ascending limb of the loop (near bottom) the ions move out down a concentration gradient
in second section (upper) ascending limb of loop Na+ and Cl- pumped out AGAINST the concentration gradient via active transport into the medulla
high concentration of Na+ and Cl- in the medulla
is the ascending limb of the loop of henle permeable to water
no (so they dont follow the Cl- and Na+ ions
describe the fluid in the ascending limb- how the concentrations change
what about conc. in tissue fluid of medulla
fluid left in the acsending limb becomes increasingly dilute
and tissue fluid in medulla developes high concentration of ions
why is it essential there is a high concentration of ions in tissue fluid of medulla
means kidney can produce urine more concentrated than the blood which is a key part of the countrcurrent multiplier system of blood
by the time dilute fluid reaches the top of the ascending limb it is ____ to blood again
this fluid then enters the____ ______ ______ and ____ ____
hypotonic
distal convoluted tubule and collecting duct
what is the function of the distal convoluted tubule
to balance the water needs of the body which also happens in the collecting duct!!
also play role of balancing the pH of blood
what means that the walls of of the tubules vary in permeability
varying levels of ADH
these cells in the tubule like the promixal ones also have many mitochondria for active transport
what does your distal convoluted tubule do if your body lacks salt
sodium ions are actively transported back out of distal convoluted tubule with chloride ions down an electrochemical gradient
can water leave the distal convoluted tubule
yes- this will concentrate the urine (if you have had little to drink say)
This is because the walls of the tubule are permeable in response to higher levels of ADH
where is the concentration and volume urine determined in the nephron
in the collecting duct
and also the distal CT
where does the collecting duct pass down
through concentrated tissue fluid of renal medulla
how does water move out of collecting duct and where does it pass through
osmosis down a conc. grad.
through renal medulla
this means the urine becomes more concentrated
water can move out of collecting duct along its whole length depending on how much water needs to be conserved
how does the level of sodium ions in fluid surrounding collecting duct change as to medulla from cortex
increases
the fluid in the collecting duct is ____ to blood when body needs to conserve water
hypotonic
hypotonic/ yellow urine
what controls how permeable the collecting duct is to water
the level of ADH so also determines how much water is reabsorbed
how would someone with one kidney need to change their diet
less protein so it doesnt need to work as hard
how would you distinguish a glomerulus under a microscope
- many nuclei in small area
- irregular arrangement of nuclei
- mass knot of capillaries
- larger than surrounding tissue
- white unstained area surrounds glomerulus
what are vasa recta
straight loop shaped capillaries near loop of henle
what does the basement membrane act as
a filter or second sieve between capillary wall and bowmans capsule
after the first layer of endothelium acts as a sieve too
which cells line the bowmans capsule
podocytes which form fenestrations
which substances are reabsorbed from prox. CT
glucose, amino acids, vitamins, 85% sodium ions and chloride ions
how are glucose, amino acids, vitamins and hormones moved back to blood in PCT
active transport with help from mitochondria which the cells in the PCT have many of
what are podocytes
foot like projections in epithelium on bowmans capsule and lumen of bowmans capsule
pod=foot
where is the net pressure gradient in the glomerulus
where is the net solute conc. grad.
from blood plasma into lumen of renal capsule with glomerular filtrate
from lumen of renal capsule to blood plasma
these gradients go through basement membrane and endothelium
What is the purpose of Kidney dialysis
Aka renal dialysis- where function of kidney is carried out artificially
What are the two types of kidney dialysis
Haemodialysis and peritoneal dialysis
What does Haemodialysis do
Where does it flow into and what does this mimic?
Uses a machine in the hospital and blood leaves the body through the artery in arm for eg
> and flows into a large machine with large SA
>where it goes between a partially permeable dialysis membrane which mimics the one in the basement membrane
What is present in the machine used in haemodialysis
What is the concentration of this stuff
Dialysis fluid which flows in and then out carrying the waste products and urea
Dialysis fluid is isotonic to the blood concentration of sugar minerals and ions
What prevents blood clotting in dialysis machine
Blood thinners
Where does the clean blood flow through when leaving the dialysis machine
Clean blood flows through bubble trap to get rid of any bubbles and then returns to vein in arm
Why must dialysis fluid be controlled carefully
To prevent loss of substances and must contain normal plasma levels of glucose to ensure there is no net movement out of blood
Also same with ions and minerals which restores the electrolyte balance of blood
Describe the concentration of urea in dialysis fluid at start
None to create a steep concentration gradient for urea so it all diffuses out of blood
What is the purpose of the countercurrent exchange system in dialysis machine
Dialysis fluid flows in different directions to maximise exchange that takes place
Haemodialysis relies on ___1/2_____?
1) steep concentration gradients
2) active transport
1) steep concentration gradients
How long and often must some one using haemodialysis treatment use the machine
What kind of lifestyle choices must someone with dialysis treatment make
4-8 hours a few times a week
Deduce intake if protein and watch diets
How is peritoneal dialysis done?
Inside body with natural dialysis membrane found in lining of abdomen called the peritoneum
True or false peritoneal dialysis takes place at home
True It can be done at home so the patient carries out their normal routine
Careful with hygiene
They have a bag and catheter attached to them
Describe the process of peritoneal dialysis
Tissue fluid introduced to abdomen using catheter and left for several hours for dialysis to take place across peritoneal membrane
-urea and excess ions pass out of blood capillaries into tissue fluid
»»and out across peritoneal membrane into dialysis fluid
Fluid is then drained off and discarded leaving blood balances
Why are transplants the best option for kidney failure patients
Long term option and healthier as long term dialysis can have serious side effects
What are the problems associated with kidney transplants
- rejection- antigens of reciprocant May differ from antigens of donor so T cells could attack kidney so patient must be on immunosuppressants which makes them susceptible to infection
- can sometimes only last 10 years so a need for another
- short supply as few people die of sudden death eg safer cars
Briefly outline how a new kidney is transplanted
Healthy kidney from donor and blood vessels are joined to the ureter and inserted into the bladder
If successful the kidney will function for many years
Dialysis and Transplants
- which is more easily accessible?
- which one means patient can live more normal lifestyle
- which is more expensive
- Dialysis more accessible
- kidney allows more normal life
- long term dialysis very expensive but so is kidney transplant
What is a proposed replacement for both dialysis and kidney transplants
Embryonic stem cells to grow kidney and hopefully without antigens!
What kind of feedback system is osmoregulation
Negative feedback
Under the control of hormones
Why must the water balance of blood be under tight control
To stop osmotic effects between tissue fluid and cells
- cells need water for metabolic processes
- too much can cause cell to swell/lysis
which receptors are sensitive to water potential of blood
osmoreceptors in the hypothalamus
which cells produce ADH
nerve cells (neurosecretory) of the hypothalamus
where is ADH stored and how does it get there?
stored in posterior pituitary gland
|»_space;but ADH gets there by passing along axon of nerve cells which terminate in the posterior pituitary gland
when is ADH released
from Posterior pituitary gland when blood water potential too low
what causes the ADH to be released into blood
action potentials, which create a wave of depolarisation, are sent down the axons from osmoreceptors in the hypothalamus
to cause ADH release into blood
how is the ADH detected and create a response
1) ADH detected by hormone receptors of cell surface membrane
2) causes Enzyme controlled reaction
with 2nd messenger cAMP
3) Vesicles containing water permeable channels called aquaporins fuse to membrane
4) more water can be reabsorbed into capillary next to kidney so urine is hypotonic (more conc.) than blood and is passed through collecting duct
why must urine have some water in it
urea is still toxic so must be dissolved in something
where does mechanism of ADH take place
specifically lumen of collecting duct and distal convoluted tubule
outline is there was a high level of water-how much ADH would be produced
secretion of ADH reduced
no binding to receptor
so no cAMP which means that no vesicles fuse
what does ADH do to the permeability of walls
and which walls does it effect and how?
increases the permeability of the distal convoluted tubule and collecting duct by binding to the cell surface receptors
how long does ADH last for
half life of 20 mins
|»_space;» broken down in blood so effects decrease over time
what does the binding of ADH to receptor cause
2nd messenger cAMP to be released
what is the function of cAMP as a 2nd messenger to ADH
causes vesicles embedded w/ the aquaporins in the membrane to fuse with the membrane on the side of the cells facing the lumen of the collecting duct
what does the aquaporin do
increases the permeability of the cell surface membrane to water so more water can enter by osmosis down a conc. grad. so water enters blood and less in urine
a GFR value below 15 means what
kidney failure
name some main causes of kidney failure
> infections - structure of podocytes and tubules damaged or destroyed
raised blood pressure damaging epithelial cells and basement membrane of bowmans cap.
genetic conditions such as polycystic kidney disease where healthy kidney tissue replaced by fluid filled cysts of damage from pressure of cysts
symptoms of kidney infection or affected by high pressure?
- protein in urine - basement membrane or podocytes no longer act as filters in bowmans capsule so large plasma proteins can pass through and out in urine
- blood in urine- another symptom that filters no longer work
symptoms and what would happen if kidney failure
- high blood pressure can cause strokes ect
- build up of toxic urea can poison cells
- loss of electrolyte balance so can’t secrete Na+,K+ Cl- ions ect which causes osmotic inbalance in tissue and death
- anemia - kidneys produce hormone erythroprotein which stimulates formation of red blood cells, without this we become tired
- pain stiffness as abnormal proteins build in blood
- weakend bones due to loss of calcium+phosphorus
what does a GFR measure
glomerular filtration rate used to indicate kidney disease
-can be done with urine sample test to measure levels of creatinine in blood which is the breakdown product of muscles
however as you age it decreases naturally and men have more muscle mass so more creatinine than women
what is GFR measured in
cm^3/min
why do birds excrete urea as uric acid
flight demands a low body mass so removing nitrogenous waste as uric acid means large amounts of water arent required. Insects do this too as they are prone to water loss
uric acid has low toxicity but more ATP required than other methods
how is uric acid formed
deamination of purines adenine and guanine
isotonic means
same concentration as/in balance with
hypotonic means
lower concentration than
hypertonic means
higher concentration than
why might sodium ions be actively pumped out of DST into blood
if body low on salt
the ______ limb of the loop of henle is permeable to Na+ and H20
descending
the _____ limb of the loop of henle is impermeable to Na+ and H20
ascending
what are the survival advantages of the loop of henle
conserves water
very concentrated urine can be produced
what does the hormone hCG stand for and what is it
human Chlorionic Gonadotrophin
results in changes in female during pregnancy and maintains uterus lining
how are pregnancy tests made? (monoclonal antibody)
antigen from hCG injected into a mouse
- clonal selection+expansion take place
- plasma cells extracted from mouse and combined with tumor cells which rapidly divide out of control
- this creates a hybridoma
- this produces lots of monoclonal antibodies with a variable region specific to hCG only
how do pregancy tests work if positive
- women wees on stick
- hCG is combined with monoclonal antibody which is linked to dye
- monoclonal antibodies connected to wall of test region and join to hCG and other MCA and the dye will show blue in the first window
- in the second window a different MCA (immunoglobulin variable protein) will recognise other MCAs which means test is done properly
how do pregnancy tests work if negative
-no hCG present means no binding of MCA to antibody in test region so goes straight through to second region where MCA joins to immunoglobulin with variable protein and shows blue to show test fin
characteristics of the specialised cells of the liver
Hepatocytes
-large nuclei, prominant Golgi, many mitochondria and metabolically very active
where does the liver recieve oxygenated blood
hepatic artery
where does the liver recieve deoxygenated blood
hepatic portal vein
section of the liver is called a
lobule
what are lobules lined with
hepatocytes
what is in the centre of the lobule
hepatic venule which joins to hepatic vein
what are sinusoids
passage for blood in liver (honeycomb like)
where is the bile made in the liver
canaliculus (lots of canaliculi) doesnt link to venule
bile drains into bile ductules which goes to the gall bladder
what are Kupffer cells
line sinusoid walls and described as fixed phagocytes (macrophage in phagocytosis)
get rid of worn out erythrocytes+leucocytes as haemoglobin has short life
what is bilirubin
pigment formed in the breakdown of haemoglobin and found in bile (makes faeces brown and lack of makes faeces white)
the hepatic artery….
carries oxygenated blood TO the liver from heart via aorta
the hepatic portal vein….
takes blood rich in products of digestion from intestines TO liver
the hepatic vein
rejoins vena cava takes deoxygenated blood out of liver
how are hepacytes involved in metabolism
homeostatic control of blood glucose concentration
insulin influemces them+ they convert glucose into storage carbohydrate glycogen
hepatocytes convert glycogen to glucose under influence of glucagon
what is transamination and when is it important
conversion of one amino acid into another
important as diet doesnt always contain required balance of amino acids so it overcomes this
what is deamination and why is it important
what role do hepatocytes play
removal of the amine group from a molecule as body can’t store proteins or amino acids (excess energy stored as fat)
any excess ingested protein would be excreted +wasted if it werent for hepatocytes
describe the ornithine cycle
the deamination of amino acids to ammonia and then to urea through enzyme controlled reactions in the ornithine cycle
remaining amino acids are used in cellular respiration or converted into lipids for storage
what is detoxification
-other metabollic pathways other than urea, produce potentially posionous substances and also things like alcohol and drugs by choice
»»liver detoxifies to make less harmful.
hepatocytes contain enzyme catalase
example of detoxification with hydrogen peroxide
catalase breaks down into oxygen and water
how does the liver detoxify alcohol
alcohol contains ethanol the active drug in drinks
-alcohol dehydrogenase breaks down ethanol to acetaldehyde and further into acetic acid and acetyl-CoA. whihc forms ethananoate (made from acetic acid) which builds up fatty acids or used in cellular respiration
how does the liver store glycogen
When blood sugar rises in the blood, insulin is released by the pancreas and travels through the blood. The insulin binds to receptor cells in the liver and receptor molecules on muscle cells, causing them to take in and store the excess glucose as glycogen.
by glycogenesis
opposite is glycogenolysis caused by glucacon and adrenaline
describe the process of ultrafiltration
> 1st step of removal of nitrogenous waste and osmoregulation
results in formation of tissue fluid in capillary beds of glomerulus and cells lining bowmans capsule
> glomerulus supplied with blood from wider afferent arteriole from renal artery and THEN leaves by narrower efferent arteriole which creates higher pressure in capillaries of glomerulus
This pressure forces blood through capillary wall and then this fluid passes through the BASEMENT MEMBRANE. This membrane is made up of collegen fibres
MOST PLASMA CONTENTS CAN GET THROUGH BASEMENT MEMBRANE BUT BLOOD CELLS AND PROTEINS ARE RETAINED IN CAPILLARY DUE TO THEIR SIZE
> podocytes in wall of bowmans capsule act as an additional filter as pedicel extensions wrap around capillaries forming slits that make sure any cells, platelets or large plasma proteins that have managed to get through epithelial cells+basement membrane DONT get into tubule itself.
describe the process of selective reabsorption
main function of the nephron after the bowmans capsule is to return most filtered substances back into the blood.
how does kidney failure effect glomerular filtration rate and electrolyte balance
> A decrease or decline in the GFR implies progression of underlying kidney disease or the occurrence of a superimposed insult to the kidneys. This is most commonly due to problems such as dehydration and volume loss. An improvement in the GFR may indicate that the kidneys are recovering some of their function.4
> When there is a malfunction of the kidneys, the balance of fluid and electrolytes can be altered, leading to an imbalance of certain electrolytes. This can, therefore, affect the transmission of impulses of the nerves and muscles throughout the body, which can have serious implications
how does liver break down ethanol
alcohol dehydrogenase enzyme breaks down ethanol to ethanal which is made into ethanoate which is used to build fatty acids or used in cellular respiration
what % of water and solutes are removed from blood plasma
20%
the filtrate reaching the loop of henle at prox convoluted tubule end is _____ to the tissue fluid surrounding the tubule
isotonic
