functions of the urinary system
1. regulation of blood volume and blood pressure
2. regulates plasma concentrations of ions
calcium - site of calcitriol synthesis (vit D)
3. controls blood pH (acid base balance)
controls acid and bicarbonate loss from blood
5. detoxifies poisons and drugs (along with liver)
general kidney anatomy
each kidney contains over one million nephron
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
1. glomerulus
the afferent arteriole and is drained by the efferent arteriole
efferent goes on to produce the peritubular capillaries filtrate
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 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
3. Bowman’s or glomerular capsule
has two layers (like a fist pushed into a
1. visceral layer
made of podocytes that are
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
contains the filtrate passing from the glomerulus
capsular space
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
tubular pole or end where the renal tubule proximal convoluted functions: reabsorbs
reabsorption is by active and passive mechanisms
epithelium also secretes substances functions: convoluted function collecting duct papillary minor calyx major calyx 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
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 functions 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
tubule to slow (more time to absorb sodium, and potassium)
1. cortical nephron- 85% are located almost entirely in
2. juxtamedullary nephrons- are located near the cortex
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
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
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
3. secretion
transport of solutes from the peritubular fluid across the tubular epithelium and into the filtrate
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
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
10% of the fluid delivered to the kidneys leaves the blood
rate is 180 (50 gal) liters per day or 70 times the blood volume everyday
average adult will reabsorb 99% of the filtrate volume
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 =
Osmotic pressures
Cap osmotic of 25 subtract capsular hydrostatic pressure of 0 = 25 mmHg (in)
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
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
the normal way to adjust GFR is to change the blood pressure at the glomerulus
autoregulation
is the ability of the kidneys to maintain a relatively stable
GFR in spite of changes in arterial blood pressure
maintains glomerular blood pressure and thus
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
decline in glomerular blood pressure results in
hormonal regulation 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
fall in renal blood pressure due to renal artery blockage
3. sympathetic activity to the JG apparatus
effects of renin -AII
a) peripheral capillary beds direct fast effect on
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
indirect and slow effect on GFR Indirect and slow effect on GFR
increase blood volume and blood pressure
indirect and slow 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
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
decreases GFR and slows the production of
moderate sympathetic activity, like during prolonged strenuous exercise, alters the pattern of blood flow and the kidney see less flow.
If autoregulation and hormonal regulation can’t oppose this change renal damage may occur due to hypoxia
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
2. very low blood pressure due to narrow efferent arteriole 3. slow flow rate
Tubular reabsorption of PCT 1. sodium (65%)
is 140 mEq/L in filtrate only 12 in tubule cell
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%)
is a transcellular route (through the cells)
once inside the cell it diffuses out the
secondary active transport
no ATP directly used must use ATP to maintain the sodium gradient
3. amino acids (100%)
are more concentrated inside the cell so will
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
5. reabsorption of other cations ions
concentrated so move in by diffusion called solvent drag
solvent drag also used to reabsorb lipid-soluble materials and vitamins
6. Chloride and other anions
negative chloride tends to follow positive
7. nitrogenous wastes
kidneys remove less then half of the urea in
uric acid is 100% reabsorbed but secreted
Tubular reabsorption of loop of Henle
Primary function is to enable the collecting duct to
concentrate the urine by conserving water
reabsorb half the remaining water and two-thirds
remember: the two parallel segments of the loop are separated only by peritubular fluid and have different permeability characteristics
1. filtrate concentration entering the loop is 300
2. concentration increases to 1200 at the bottom of
3. concentration drops from 1200 to 100 as the
remember the surrounding tissue will have similar
1. sodium, potassium and chloride are pumped out of the thick ascending limb by a sodium, potassium, 2 chloride cotransporter
the concentration of salts within the loop goes from
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
countercurrent multiplication countercurrent
multiplication effect
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
filtrate is only 15-20% of original volume
electrolyte and waste concentration are no longer similar to
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
this sodium transport is selectively controlled based on the bodies needs by the hormone aldosterone
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
2. also site of calcium reabsorption
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 water reabsorption occurs if ADH is present
filtrate has a osmolarity of 100 as it enters the collection system
ANF effects
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
most occurs in the distal convoluted tube
potassium hydrogen ion
occurs when blood and filtrate pH is low
this diffuses into kidney cells which have carbonic anhydrase
the bicar will enter the blood and buffer pH
ammonium
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
the bicarb will enter the blood to buffer pH
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r 3 ^ F o ™ e l n ' m e i s t f a r b i 8 Landes-Lehrer-ßibliothek des Fürstentums Liechtenstein Georg Thieme Verlag Stuttgart • New York 1987 Inhaltsverzeichnis Vorwort zur 11. Auflage V Generelle Prinzipien 1 Kapitell 1. Aufgaben der Pharmakologie 1 2. Heuristische Prinzipien in der Pharmakologie 2 2.1 Rezepttheorie 3 2.2 Struktur-Wirkungs-Beziehungen 6 2.3 Rezepto