Structure and Function of
the Kidneys
Functional
unit is the nephron
Function:
Regulation of extracellular fluid by urine formation
Regulates:
1.
Blood volume/blood pressure
2.
Concentration of wastes
3.
Concentration of Na+, K+, HCO3-
4.
pH of plasma
Structure:
2 kidneys below diaphragm
Size
of a fist
Renal
Pelvis-Ureters-Urinary bladder.
Cortex
Medulla
composition:
8-15
renal pyramids, separated by renal columns
Calyces
join to form renal pelvis
Kidney
stones:
1.
Calcium oxalte
2.
Calcium phosphate
3.
Uric Acid
4.
Cystine
Urethra
is 4 cm in women, 20 cm in men
2
sphincters: upper internal urethral sphincter
Voluntary:
lower external urethral sphincter.
Micturition Reflex:
urination.
Reflex
center at 2,3,4 sacral levels of spinal cord. Internal relaxes, urgency and
external relaxation is under voluntary control. Ability develops at 2-3 years of
age.
Microscopic Structure of
Kidney
Each
kidney has 1 million nephrons
Renal Blood Vessels
Arterial
blood, renal artery, interlobar arteries, Arcuate arteries, interlobar arteries,
afferent arterioles, glomeruli efferent arteriole, peritubular capillaries,
interlobar veins, arcuate veins, interlobar veins, renal vein, inferior vena
cava
Nephron
Glomerular
capsule: in cortex, Bowman's Capsule
Proximal
Convoluted tubule: in cortex, Cubodial
cells with lots of microvilli
Loop
of Henle: in medulla
Descending
limb
Ascending
Limb
Distal
Convoluted Tubule: cortex
Collecting
Duct
Juxamedullary
nephrons: Originate in inner 1/3 of cortex. Longer loops.
Cortical
nephrons: originate in outer 2/3 of cortex
Polycystic
Kidney disease: develops in middle age, autosomal dominant trait. Cysts on renal
tubules.
Urine
collects in collecting duct, minor calyx, renal pervis-ureter.
Glomerular Filtration
Glomerular
capillaries have pores (fenestral)
RBC,
WBC, platelets can't be filtered.
Inner
layer of glomerular capsule are cells called podocytes (shaped like octopus)
which form a web like clasped hands, which wrap the capillaries forming slits as
passageway for filtered molecules.
Proteins
don't usually go into filtrate.
Glomerular Ultrafiltrate
Net
filtration pressure is 10 mmHg
Due
to large surface area of glomerular capillaries a lot of filtrate is produced
Glomerular
filtration rate(GFR) Volume/minute of both kidneys.
115ml/min
women, 125ml/min in men.
All
blood filtered every 40 minutes, 180L/day…water is reabsorbed.
Regulation GFR
Vasoconstriction
or vasodilation of afferent arterioles
Extrinsic:
Sympathetic innervation
Intrinsic
regulation mechanism: renal autoregulation
Sympathetic Nerve Effects
Constriction
of afferent arterioles.
Renal Autoregulation
MAP
may change but GFR does not.
Pressure
changes direct constriction or dilation of afferent arterioles.
Increase
in filtrate volume sensed at ascending limb. Increase in fitrate=constriction.
Called
tubuloglomerular feedback.
Reabsorption of Salt and
Water
Water
follows salt by osmosis
Most
salt and water reabsorbed at proximal tubule
Remaining
water reabsorbed at collecting duct.
180
L of filtrate produces 1-2 Liters of urine in 24 hours.
1%
of filtrate is excreted.
400ml
urine/day is minimum
Since
the filtrate solute concentration is the same as plasma solute concentration
(300mOsm) solutes need to be reabsorbed to blood.
Proximal Tubule
Has
lots of microvilli and mitochondria
Active
and Passive Transport
Basal
and lateral sides of cells have Na/K pumps that keep Na concentration low in the
cell.
NA+
diffuses into apical side of cell. Cl- passively follows.
Water
follows salt.
All
returns to blood.
65
% of salt and water in filtrate is returned at proximal tubule.
20
% returned at Descending limb, no hormonal control, 6 % of energy expense.
15%
returned later and hormone are involved.
Countercurrent Multiplier
System
The
renal medulla is 4 x as saltly as the filtrate due to juxtamedullary nephron
Ascending
Limb: extrudes salt
Sodium
diffuse out
K+,
and CL- moves by secondary active transport.
Na+
actively transported to interstial fluid.
Not
permeable to water.
Descending Limb(20 % of salt
and water returned to blood here)
Not
permeable to salt
Permeable
to water.
Water
leaves via diffusion.
Countercurrent
Multiplication
As
you move from cortex to medulla, it gets more and more salty. This is a feature
of the descending(water leaves) and ascending loop moving in opposite
directions, and the active extrusion of salt from the Ascending
limb.
Vasa Recta: capillary-like
Maintains
the salt concentration by removing the water that comes out of filtrate, but
leaving the salt in the medulla.
Urea
transporters
Aquaporin
proteins
Countercurrent
exchange: attracts water but extrudes urea and salt out at ascending limb.
Urea
Extruded
from thin segment of loop of henle and collecting duct.
Collecting Duct: ADH
Collecting
duct impermeable to salt but is permeable to water. Urine is hypotonic compared
to interstitial fluid in this region.
Water
returned to circulation.
The
rate of water reabsorption at this region determined by water permeability of
collecting duct.
This
depends on the number of aquaporins.
1.
ADH binds to receptor proteins on
collecting duct.
2.
cAMP is activated.
3.
Exocytosis of vesicles from golgi
that have aquaporins.
4.
No ADH the aquaporins are removed
via endocytosis.
Osmoreceptors
in hypothalamus trigger ADH release from Posterior Pituitary.
Diabetes
insipidus is when not enough ADH secreted.
Renal Plasma Clearance
Waste
is removed from blood.
Tubular Secretion
Secretion
is the active process of eliminating wastes/toxins by passing them to urine.
Drugs
Proximal
tubule has receptors that will select a variety of products to be eliminated.
Some
drugs block secretion of antibiotics and increase effectiveness of these drugs.
GFR
Inulin
a polymer of fructose is used to measure GFR. It is not reabsorbed or secreted.
Quantity
excreted per minute mg/min=V ml/min x Umg/ml
Quantity
filtered per minute mg/min=GFR ml/min x Pmg/ml
GFR
x P = V x U
GFR=
V X U/P
Inulin
120 ml/min clearance
Creatine
used to check GFR in practice.
Calculations
Renal
Plasma Clearance is volume of plasma from which substance totally removed in one
minute by kidney.
Renal
Plasma Clearance = V xU/P
Urea Clearance
75ml/min
Some
urea is reabsorbed
PAH
Measurement
of renal blood flow
It
is possible for all of a substance to be cleared in a single pass even though
not all blood is filtered. This occurs by secretion. PAH is a substance that can
be cleared. 625 ml/min.
Take
into account that RBC take up space in blood. Calculate volume and divide by
plasma volume to get the total real blood flow.
Glucose
Glucose
and amino acids are reabsorbed at proximal tubule.
Carrier
mediated transport can become saturated.
Transport
maximum.
Normally
only 125 mg/min of glucose in tubules.
325
mg/min is transport maximum.
When
glucose is 180 mg per 100ml glucose gets into urine.
Called
renal plasma threshold for glucose.
Normal
glucose is 1mg/ml.
Diabetes
mellitus is when there is not enough secretion of insulin
Lots
of urine to help get glucose out.
Electrolyte and Acid-Base
Balance
Kidneys
regulate
Na+--important
for regulation of blood volume and pressure
K+--important
for regulation of cardiac and skeletal muscles.
Hco3-
H+
Aldosterone(Adrenal cortex)
90
% of Na and K reabsorbed before distal tubule.
Cortical
collecting duct and distal tubule reabsorb varying amounts depending on need.
Controlled
by Aldosterone.
Sodium reabsorption
30
g Na secreted in urine per day, unless aldosterone involved.
Max
aldosterone secreted, then NO NA in urine!
Mostly
occurs at cortical collecting duct.
Potassium Secretion
High
K in blood stimulates Aldosterone secretion
Increase
in Na reabsorption and secretion of K increases.
Diuretics
increase Na secretion at distal tubule. This increases K secretion and loss.
Wrong
amount of K leads to heart problems.
Aldosterone Secretion
Promotes
Na retention
K
loss
Concentration
of Na and K changes aldosterone secretions.
Juxtaglomerular Apparatus
Afferent
arteriole comes in contact with ascending limb of loop.
Cells
in this region secrete renin.
Angiotensinogen
converted to angiotensin 1 by renin.
Angiotensin
1 converted to angiotensin 2 by ACE.
ACE
in lungs.
Angiotensin
2 stimulates adrenal cortex to secrete aldosterone.
Renin Secretion
Not
enough salt in diet leads to a fall in blood volume.
Decreased
blood volume causes increased renin secretion.
Granular
cells are baroreceptors.
Sympathetic
nervous system can stimulate this when it detects decrease in blood volume.
Good
example of negative feedback (retain more Na, blood volume rises).
Macula
Densa
Cells
in ascending limb called macula densa can inhibit renin secretin when blood Na
is raised.
Atrial Natriurectic Peptide
Increase
in blood volume stretches atria and increases ANP.
ANP
promotes the excretion of Na and water in urine
Endogenous
diuretic
Sodium, potassium, and H+
K+
concentration and H + concentration are related
Extracellular
H+ concentration goes up, and H+ moves in to cell
K+
then moves out.
In
Distal tubule and cortical collecting duct, K+ and H+ secreted to urine when Na+
reabsorbed.
When
acid blood, then more H+ secreted, but not as much K+ leading to too much K+ in
blood.
When
K+ secreted not enough H+ is secreted.
Not
enough K+ it can be reabsorbed by collecting duct.
Addison's
disease is not enough aldosterone (which would promote secretion of K+ and H+)
leads to acidosis and hyperkalemia.
Acid-Base regulation
Excrete
H+ and reabsorb bicarbonate.
H+
goes in filtrate, is secreted at proximal tubule(antiport with Na+).
In
filtrate bicarbonate turned to CO2 which diffuses into apical cells and turns
back to bicarbonate.
High
elevation: Low Pco2, alkalosis
Excrete
bicarbonate
pH
lowers.
Inhibit
renal carbonic anhydrase,
Stop
reabsorbtion of bicarbonate
Treat
Acute Mountain Sickness
Buffers
H+
in urine buffered by HPO4 2-(H2PO4) , and NH3(ammonium)
Diuretics
Lower
blood volume with diuretics
Hypertension,
congestive heart failure, edema
Loop
diuretics: most powerful, stop Na+ movement out of loop,
Thiazides:
stop salt and water reabsorption at distal convoluted tuble.
Carbonic
anhydrase inhibitors: stop bicarbonate reabsorption and water that goes with it.
Weak.
Osmotic
diuretics: extra solutes in filtrate
Potassium-sparing
diuretics: Aldosterone agonist, or blocks Na+ reabsorption and K+ secretion
If
you don't have enough K+ you have heart problems and neurological problems.
Supplement diuretics with K+ supplement and low salt diet.
Renal Function Tests and
Kidney Disease
Real
plasma clearance of PAH
Measurement
of GFR via inulin clearance
Creatine
concentration in plasma
Urinary
albumin levels--hypertension and diabetes can damage the kidney.
Acute Renal Failure
Sudden
loss of ability to excrete waste, regulate blood volume, pH and electrolyte
balance.
NSAIDS
can cause this as can reduced blood flow, inflammation, atheriosclerosis.
Glomerulonephritis
Strep
infection
Autoimmune
response
Damage
to glomerula
Protein
leak into urine.
Edema.
Renal Insufficiency
Leads
to hypertension
Uremia
Acidosis
High
K+ concentration
Uremic
Coma
Dialysis
CAPD
in patients abdomen