Chapter 26

advertisement
Chapter 26
Urinary System
consists of
paired kidneys
paired ureters
one urinary bladder
one urethra
functions of the urinary system
1. regulation of blood volume and blood pressure
control of water lost in urine
release of erythropoietin
release of renin
2. regulates plasma concentrations of ions
sodium, potassium, chloride
calcium - site of calcitriol synthesis (vit D)
3. controls blood pH (acid base balance)
controls acid and bicarbonate loss from blood
4. eliminates organic wastes
especially nitrogenous wastes
ammonia, urea and uric acid
5. detoxifies poisons and drugs (along with liver)
6. deaminates amino acids
so can be converted to glucose ect
general kidney anatomy
nephron
each kidney contains over one million nephron
these are the blood filtering units
parts of the nephron
each nephron is composed of a blood supply called the
renal corpuscle and a long tube called the renal tubule
I) renal corpuscle
is the blood supply of the nephron called the
glomerulus and the tissue that surrounds the
glomerulus called the Bowman’s capsule
1
1. glomerulus
tuft of 50 intertwining fenestrated capillaries
receives blood from the afferent
arteriole and is drained by the
efferent arteriole
efferent goes on to produce
the peritubular capillaries
have very high blood pressure for a
capillary
due to small efferent
arteriole
thus a great quantity of fluid
and solutes are pushed
out
this fluid is called the
filtrate
very similar to plasma
but very little protein
thus has lots of good
stuff the body needs
back
over 90% of filtrate is
reabsorbed in the peritubular
capillary beds which
surround the nephron tube
2. mesangila cells
between neighboring capillaries there are
mesangila cells
mesangila cell function
1. are resident macrophages that
remove materials that exits the cap
but can not enter the renal tube
2. provide some physical support for
cap.
3. contain actomyosin and can
contract or relax changing cap
diameter and may regulate filtration
rate
2
3. Bowman’s or glomerular capsule
surrounds the glomerulus
has two layers (like a fist pushed into a
balloon)
1. visceral layer
(inner most layer)
made of podocytes that are
in contact with glomerulus
podocytes form foot processes
(pedicels) on the glomerulus which
form filtration slits or slit pores so
that filtrate can exit the capillaries
the filtration slit, the fenestrated
endothelium, and the lamina densa
between the two make up the
filtration membrane which
determines what can leave the
capillary and enter the capsule as a
filtrate
filtration membrane is affected
during glomerulonephritis or
inflammation of the glomeruli
2. parietal layer
outer layer of simple squamous
epithelium
contains the filtrate passing from the
glomerulus
capsular space
a space between the two layers
fluid pressure will build here and
force the filtrate down the renal
tubule
the Bowman’s capsule has a vascular pole
or end where the capillaries enter and a
3
tubular pole or end where the renal tubule
starts
II) renal tubule
1 proximal convoluted tubule
arises from tubular pole of the capsule
constructed of cuboidal epithelial cells
have numerous microvilli for
absorption and large concentration of
mitochondria
functions:
reabsorbs
most nutrients
most ions
any plasma proteins that
escape
fluid by osmosis
follows nutrients and
ions
reabsorption is by active and passive
mechanisms
epithelium also secretes substances
into PCT lumen from blood
2. loop of Henle
1. descending limb
2. ascending limb
each limb has a thick and thin
segment (cells size different tube
diameter the same)
functions:
thick ascending limb pumps out
NaCl but not permeable to water
important in concentrating urine
3. distal convoluted tubule
passes between afferent and efferent
arterioles
smaller diameter then PCT and cells lack
microvilli
4
function
1. active secretion of ions, acid
drugs and toxins
2. selective reabsorption of Na and
Ca
3. the selective reabsorption of water
Collecting system
DCT empties into a
collecting duct
several collecting ducts empty into
papillary ducts
papillary ducts empty into
minor calyx
minor calyx empty into
major calyx
major calyx empty into
renal pelvis
collecting system adjusts the finial composistion of
the filtrate controlling the final osmotic
concentration and volume of urine
juxtaglomerular apparatus
located where the distal tubule lies against the afferent and efferent
arteriole
1. juxtaglomerular cells
specialized smooth muscle cells located in the wall of the
afferent arteriole
functions: the release of renin
JG cells function as a blood pressure receptor which
releases renin when pressure drops
JG cells also are innervated by the sympathetic
nervous system which triggers the release of renin
JG cells also releases erythropoietin in response to
low pressure and low O2
2. macula densa
cells of the distal convoluted tubule
are taller columnar cells
5
functions as chemoreceptors
sensitive to changes in the solute levels (sodium) of
the filtrate in the distal convoluted tubule
a decline in osmolarity of fluid in DCT triggers
renin release
occurs when fluid moves through nephron
tubule to slow (more time to absorb sodium,
and potassium)
types of nephron
1. cortical nephron- 85% are located almost entirely in
the cortex of the kidney
except small part of the loop of Henle
they have a short loop of Henle
2. juxtamedullary nephrons- are located near the cortex
medulla junction
loop of Henle plunges deeply into the medulla
have a longer loop then the cortical nephrons
important in producing a concentrated urine
Urine formation
kidneys filter entire blood volume 60 times per day
entire volume every 40 minutes
are 1% of body weight but consume 20-25% of oxygen at rest
the object is to regulate the volume and composition of the blood to maintain
homeostasis
of particular importance is the clearance of three organic waste products
urea: 21 grams/day from the breakdown of amino acids (actually
is converted from ammonia)
creatinine: 1.8 grams/day from the breakdown of creatinine
phosphate by the skeletal muscle
uric acid: 480 mg/day formed from the breakdown of RNA and
DNA
urine formation involve three processes
1. glomerular filtration
2. tubular reabsorption
the removal of water and solutes from the filtrate
eventually inter the peritubular capillaries
6
3. secretion
transport of solutes from the peritubular fluid across the tubular
epithelium and into the filtrate
common for many drugs and toxins
1) glomerular filtration
is a passive process in which fluids and solutes are forced across the wall
of the glomerulus by hydrostatic pressure
filtration membrane: the filtration slit, the fenestrated endothelium, and
the lamina densa between the two
it is the barrier that the filtrate crosses passing from the glomerulus
to the Bowman’s capsule
determines what can leave the capillary and enter the
capsule as a filtrate
fenestrated endothelium prevents cells from passing
lamina densa blocks all but the smallest plasma
proteins
filtration slits block small plasma proteins only
allowing ions nutrients and water to cross
glomerular filtration rate (GFR)
total amount of filtrate formed per minute by the kidneys
125 ml per minute
10% of the fluid delivered to the kidneys leaves the blood
stream into the capsular spaces
rate is 180 (50 gal) liters per day or 70 times the blood
volume everyday
average adult will reabsorb 99% of the filtrate volume
excrete 1 to 2 liters of urine per day
GFR is controlled by the same forces that control filtration/reabsorption at
capillary beds (balance between hydrostatic pressures and osmotic
pressures)
Hydrostatic pressures
Bp of 50 subtract capsular hydrostatic pressure of 15 =
35mmHg(out)
Osmotic pressures
Cap osmotic of 25 subtract capsular hydrostatic pressure of
0 = 25 mmHg (in)
7
Filtration pressure = 35(out) – 25 (in ) or 10mmHg(out)
two factors that result in glomerular filtration being high
1. filtration membrane is 1000 times more permeable (fenestrated)
2. glomerular blood pressure is higher then at a cap bed (50
verses 15 mmHg)
due to small diameter of the efferent arteriole
GFR must be carefully controlled
If filtrate flow is to fast, can’t reabsorb sufficient solutes and water
(loss of nutrients and blood volume)
If too slow, blood levels of wastes increase and results in
reabsorption of wastes that should be eliminated
regulating GFR
the normal way to adjust GFR is to change the blood pressure at
the glomerulus
this is achieved by three mechanisms
1. autoregulation of GFR
2. hormonal regulation
3. sympathetic regulation
autoregulation
is the ability of the kidneys to maintain a relatively stable
GFR in spite of changes in arterial blood pressure
the nephron maintains glomerular blood pressure and thus
GFR by
1. changing the diameter of the afferent arteriole
2. changing the diameter of the efferent arteriole
The changes in diameter are the result of the effect
that stretch has on smooth muscle contractions in
the wall of the vessel
increase in glomerular blood pressure
1. afferent arteriole wall is stretched by pressure
which stimulates smooth muscle contraction
2. constriction of mesangial cells
3. relaxation of efferent arterioles
decline in glomerular blood pressure results in
1. dilation of the afferent arterioles
8
2. relaxation of mesangial cells
3. constriction of efferent arterioles
hormonal regulation of GFR
renin – angiotensin
works to increased systemic blood volume and
blood pressure and the restoration of normal GFR
1. renin from the juxtaglomerular cells is released
by a drop in glomerular blood pressure due to
low blood volume
fall in systemic blood pressure
fall in renal blood pressure due to
renal artery blockage
2. low osmolarity of fluid in DCT
occurs when GFR is very slow and fluid
moves through nephron tubule to slow
3. sympathetic activity to the JG apparatus
effects of renin -AII
renin - angiotensin I - angiotensin IIaldosterone
a) peripheral capillary beds
AII causes vasoconstriction of
arterioles
will elevate pressure in renal
arteries
direct fast effect on
GFR
b) at nephron
AII constricts efferent arterioles
Direct fast effect of GFR
Triggers the release of aldosterone
stimulates reabsorption of Na and
water by DCT and collecting system
increased blood volume and
increased systematic blood
pressure
indirect and slow
effect on GFR
c) CNS
9
AII triggers releases of ADH which
increases water reabsorption
from DCT and collecting
system
Indirect and slow
effect on GFR
AII stimulates thirst which will
increase blood volume and blood
pressure
indirect and slow
effect on GFR
atrial natriuretic peptide
main role is to lower blood volume and pressure
released by stretch on the atrial wall by high BP
ANP triggers dilation of afferent arteriole and
constriction of efferent arteriole
This will increase GFR so produce more urine and
thus lower blood volume and blood pressure
ANP blocks the affects of ADH so lose
water and sodium
sympathetic regulation of GFR
most nerve fibers are sympathetic fibers
are activated during high levels of sympathetic activity
especially by acute drastic fall in blood pressure
will override all other forms of GFR regulation
effects on GFR
fibers produce powerful vasoconstriction of afferent
arterioles
decreases GFR and slows the production of
filtrate
moderate sympathetic activity, like during
prolonged strenuous exercise, alters the pattern of
blood flow and the kidney see less flow.
10
If autoregulation and hormonal regulation
can’t oppose this change renal damage may
occur due to hypoxia
Common in endurance events
Proteinuria (protein in urine)
Hematuria (blood in urine)
conversion of the filtrate to urine involves the recovery of useful substances by tubular
reabsorption and the disposal (tubular secretion) of undesirable solutes that did not leave
the blood stream during filtration
2) tubular reabsorption
Typically almost 99% of the filtrate volume and salts content, and almost
100% of the glucose and amino acids will be reabsorbed by the renal
tubule
This material is returned to the peritubular capillaries by diffusion
movement into the peritubular capillaries is easy to do
1. have high colloid osmotic pressure
2. very low blood pressure due to narrow efferent
arteriole
3. slow flow rate
Tubular reabsorption of PCT
Major chemicals reabsorption at PCT
1. sodium (65%)
is 140 mEq/L in filtrate only 12 in tubule
cell
cells are relatively permeable to Na
so much enters by simple diffusion
once inside the cell it is pumped out the
other side by the sodium/potassium ATP-ase
sodium is also reabsorbed by cotransport
with other nutrients
2. glucose (100%)
transported into the cell by glucose-sodium
cotransport proteins
is a transcellular route (through the
cells)
glucose uses the large concentration
gradient
of sodium to be pulled in
glucose is more concentrated inside
11
the tubule cell
once inside the cell it diffuses out the
other side by facilitated diffusion
it is a case of secondary active transport
no ATP directly used
must use ATP to maintain the
sodium gradient
3. amino acids (100%)
moved the same way as glucose
amino acid-sodium cotransport
proteins
are more concentrated inside the cell so will
diffuse out of tubule cells
both amino acids and sugars require a transport
protein which are limited in number thus there is a
transport maximum
if filtrate moves too fast (high GFR) or
levels of sugars or amino acids are too high
the transporters will become saturated and
the nutrients will pass out in the urine
diabetes mellitus = sugar in the
urine
4. reabsorption of water(65%)
as nutrients and ions reabsorbed the filtrate
becomes more concentrated with water
water will then flow by osmosis
5. reabsorption of other cations ions
K, Ca, Mg, ect.
As water leaves remaining ions become
concentrated so move in by diffusion
called solvent drag
solvent drag also used to reabsorb lipidsoluble materials and vitamins
6. Chloride and other anions
negative chloride tends to follow positive
12
sodium
also reabsorb by solvent drag
7. nitrogenous wastes
urea is absorbed by solvent drag (60%)
kidneys remove less then half of the urea in
each pass
uric acid is 100% reabsorbed but secreted
back in the distal convoluted tubule
creatinine is not reabsorbed at all
Tubular reabsorption of loop of Henle
Primary function is to enable the collecting duct to
concentrate the urine by conserving water
what happens here?
reabsorb half the remaining water and two-thirds
the
remaining Na, K, and Cl
remember: the two parallel segments of the loop are
separated only by peritubular fluid and have different
permeability characteristics
facts:
1. filtrate concentration entering the loop is 300
mosm
2. concentration increases to 1200 at the bottom of
the loop
3. concentration drops from 1200 to 100 as the
filtrate enters the DCT
remember the surrounding tissue will have similar
osmolarity as the filtrate
1. sodium, potassium and chloride are pumped out of the
thick ascending limb by a sodium, potassium, 2 chloride
cotransporter
this area is not permeable to water
13
the concentration of salts within the loop goes from
1200 down to 100
DCT receives a solution of 100mosm
most solutes are now wastes
the pumping of Na, K, Cl results in a concentrated
salt fluid in the tissues around the descending limb
with the bottom being most concentrated 1200
mosm
2. the thin descending limb is permeable to water but not
salts so water flows out of the thin descending limb
attracted to the salt pumped out by the thick ascending limb
this increases the concentration of the salts in the
filtrate as you move alone the thick ascending limb
toward the bottom 300 to 1200 mosm at the bottom
makes it easier to pump out Na,K and Cl in
the ascending limb
the vasa recta, with is a part of the peritubular
capillary bed, parallels the loop so that the salt
gradient is established in the vasa recta so not to
disturb the salt gradient and yet it picks up the
excess water and salts
called countercurrent multiplication
countercurrent
exchange occurs between fluids
moving in opposite directions
multiplication
effect of exchange increases as fluid
movement continues
the fluid entered the loop at 300 mosm. Only half of this volume will
enter the DCT and it will be at 100mosm due to the reabsorption of NaCl
and K by the ascending limb. This solution will also have high
concentrations of urea and other wastes that were not transported out
Tubular reabsorption and secretion of distal convoluted
tubule
filtrate is only 15-20% of original volume
14
electrolyte and waste concentration are no longer similar to
plasma
selective reabsorption along the DCT makes adjustmenst in
the composition and volume of the filtate
reabsorption
1. sodium reabsorption
Sodium is actively transported out of filtrate
in exchange from potassium
more sodium gained then potassium lost so
increases water absorption
this sodium transport is selectively
controlled based on the bodies needs by the
hormone aldosterone
aldosterone is released in response to
AII
Low blood sodium
High blood potassium (weak)
aldosterone’s affects include
1. trigger the production and
insertion of a sodium channel in the
basal membrane
2. stimulate the synthesis and
activity of the sodium-potassium
ATPase
thus aldosterone triggers sodium
reabsorption but also potassium loss
so can cause
hypokalemia
atrial natriuretic factor
inhibits the effects of aldosterone
(don’t forget ADH too) on sodium
and water reabsorption in DCT
thus reduces blood volume
and pressure
15
2. also site of calcium reabsorption
regulated by parathyroid and calcitriol
affects
1. stimulate the production of a
calcium channel
2. stimulate the production and
activity of a calcium pump (Ca-H
ATPase)
Tubular reabsorption of collecting system
sodium- in cortical region aldosterone-sensitive
sodium reabsorption occurs
same as DCT
water reabsorption occurs if ADH is present
filtrate has a osmolarity of 100 as it enters
the collection system
passes by the loop of Henle
where tissue has aosmolarity of up to
1200
if ADH present the system becomes
permeable to water and it moves by
osmoses
thus with out ADH urine will be 100
mosm or dilute
diabetes insipidus
with max ADH urine will be near
1200 mosm or very concentrated
natriuretic
ADH effects are opposed by atrial
peptide
ANF effects
1. elevates GFR
2. blocks aldosterone effects
along DCT and collecting
system
3. blocks ADH effects on
collecting system
4. blocks release of
aldosterone and ADH
16
Urea reabsorption
The distal portion of the collecting system is
permeable to urea which is concentrated by
the movement of water out of the collecting
system
Now urea will travel down its contrition
gradient and collects here the bottom of the
loop
2) tubular secretion
movement of substances from the peritubular capillaries into the tubule
occurs if have a concentration gradient
most occurs in the distal convoluted tube
potassium
is secreted in exchange for sodium
hydrogen ion
occurs when blood and filtrate pH is low
low pH (high hydrogen ion ) results in
formation of CO2
this diffuses into kidney cells which have carbonic
anhydrase
this converts CO2 to H2CO3
breakdown to H + HCO3
DCT cells pump out H in exchange for
sodium
thus acidify the urine
the bicar will enter the blood and buffer pH
ammonium ion
when blood pH drops DCT and PCT will be
stimulated to deaminate amino acids producing
NH3 (ammonia)
the ammonia will bind to H from the break
down of H2CO3 (or other sources) and
produce NH4 (ammonium ion which will be
transported into the tubule by sodium
cotransport
the bicarb will enter the blood to buffer pH
17
18
Download