Transcript Kidney

Dr Gihan Gawish
Dr Gihan Gawish
Function
• Maintains homeostasis
• Removing metabolic waste (except CO2)
– e.g. ammonia, urea, uric acid
• Removing foreign compounds
– e.g. drugs, food additives, pesticides
• Regulating salt concentrations, fluid volume,
and pH
Dr Gihan Gawish
Anatomy
• Kidneys (2)
– process plasma into urine
• Ureters (2)
– tubes that carry urine to bladder
• Urinary bladder
– storage of urine
• Urethra
– carries urine to exterior
Dr Gihan Gawish
Anatomy
• Cortex
– outer granular region
• Medulla
– inner striated region
– renal pyramids
• Renal Pelvis
– central collecting cavity
• Renal artery and vein
Dr Gihan Gawish
Anatomy
• Nephron
– 1 million per kidney
– functional unit of the kidney
– smallest unit capable of forming urine
Dr Gihan Gawish
Nephron
• Vascular Component
– conducts blood
• Renal Artery
• Afferent Arteriole
• Glomerulus
• Efferent Arteriole
• Peritubular Capillaries
• Venules
• Renal Vein
Dr Gihan Gawish
Nephron
• Tubular Component
• – forms urine
• Bowman’s capsule
• Proximal Convoluted Tubule
• Loop of Henle
• Distal Convoluted Tubule
• Collecting duct
Dr Gihan Gawish
Dr Gihan Gawish
Urine Formation
• Urine - water and waste solutes
• Nephrons conduct three processes to convert blood
plasma into urine
1. filtration
filter blood plasma to retain cells/proteins
2. reabsorption
remove valuable materials from filtrate
3. secretion
•
transfer additional wastes to filtrate
Dr Gihan Gawish
Filtration
• Filtration driven by blood pressure
• Glomerular filtration is nonselective
• – Small particles pass (glucose, Na+,
urea, H2O)
• – Large ones do not
• 20% of plasma enters tubule
– plasma filtered 65x/day
Dr Gihan Gawish
Reabsorption
• Occurs in remainder of nephron tubule
• Selective movement of substances from tubule
into plasma
– Return of valuable substances to peritubular
caps
• Active or passive
– Passive (no energy)
– Active transport (requires energy)
Dr Gihan Gawish
Secretions
• Also occurs in tubules
• Additional materials transported from
plasma in Peritubular capillaries into
tubule
• – excess K+, Ca2+ and H+, uric acid
• – foreign compounds
• By passive diffusion or active carrier
transport
Dr Gihan Gawish
Formation of Urine steps:
1. Blood enters
pressure.
the
glomerulus
under
2. This causes water, small molecules (but
not macromolecules like proteins) and
ions to filter through the capillary walls
into the Bowman's capsule. This fluid is
called nephric filtrate.
Dr Gihan Gawish
Formation of Urine steps
3. Nephric filtrate collects within the Bowman's capsule
and then flows into the proximal tubule.
4. Here all of the glucose, and amino acids, >90% of the
uric acid, and ~60% of inorganic salts are reabsorbed
by active transport.
5. The active transport of Na+ out of the proximal tubule
is controlled by angiotensin II.
6. The active transport of phosphate (PO43-) is regulated
(suppressed by) the parathyroid hormone.
Dr Gihan Gawish
Formation of Urine steps
7. As these solutes are removed from the nephric filtrate, a large
volume of the water follows them by osmosis (80–85% of the 180
liters deposited in the Bowman's capsules in 24 hours).
8. As the fluid flows into the descending segment of the loop of Henle,
water continues to leave by osmosis because the interstitial fluid is
very hypertonic.
9. This is caused by the active transport of Na+ out of the tubular fluid
as it moves up the ascending segment of the loop of Henle.
10. In the distal tubules, more sodium is reclaimed by active transport,
and still more water follows by osmosis.
11. Final adjustment of the sodium and water content of the body occurs
in the collecting ducts.
Dr Gihan Gawish
Formation of Urine steps
• Sodium
Although 97% of the sodium has already
been removed, it is the last 3% that
determines the final balance of sodium —
and hence water content and blood pressure
— in the body.
The reabsorption of sodium in the distal
tubule and the collecting ducts is closely
regulated, chiefly by the action of the
hormone aldosterone.
Dr Gihan Gawish
Formation of Urine steps
Water
• The hypertonic interstitial fluid surrounding
the collecting ducts provides a high
osmotic pressure for the removal of water.
• Transmembrane channels made of
proteins called aquaporins are inserted in
the plasma membrane greatly increasing
its permeability to water.
• (When open, an aquaporin channel allows
3 billion molecules of water to pass
through each second.)
Dr Gihan Gawish
Water
• Insertion of aquaporin-2 channels requires
signaling by vasopressin (also known as
arginine vasopressin [AVP] or the antidiuretic
hormone [ADH]).
– Vasopressin binds to receptors (called V2 receptors) on the
basolateral surface of the cells of the collecting ducts.
– Binding of the hormone triggers a rising level of cAMP within the
cell.
– This "second messenger" initiates a chain of events culminating
in the insertion of aquaporin-2 channels in the apical surface of
the cell.
Dr Gihan Gawish
Formation of Urine steps
Dr Gihan Gawish
Formation of Urine steps
• The release of vasopressin (from the posterior lobe of
the pituitary gland) is regulated by the osmotic
pressure of the blood.
• Anything that dehydrates the body, such as perspiring
heavily,
– increases the osmotic pressure of the blood;
– turns on the vasopressin → V2 receptors → aquaporin-2
pathway.
Dr Gihan Gawish
Formation of Urine steps
• The result:
– As little as 0.5 liter/day of urine may remain of
the original 180 liters/day of nephric filtrate.
– The concentration of salts in the urine can be
as much as four times that of the blood. (But
not high enough to enable humans to benefit
from drinking sea water, which is saltier still.)
Dr Gihan Gawish
Formation of Urine steps
• If the blood should become too dilute (as would
occur after drinking a large amount of water(
• Vasopressin secretion is inhibited .
• The aquaporin-2 channels are taken back into
the cell by endocytosis.
• The result: a large volume of watery urine is
formed (with a salt concentration as little as onefourth of that of the blood.
Dr Gihan Gawish
In 24 hours the kidneys reclaim
• 1,300~g of NaCl
• 400~g NaHCO3
• 180~g glucose
• almost all of the 180 liters of water that entered
the tubules.
Dr Gihan Gawish
Diabetes insipidus
• This disorder is characterized by:
• excretion of large amounts of a watery urine (as much as
30 liters — about 8 gallons — each day!)
• unremitting thirst.
• It can have several causes:
• Insufficient secretion of vasopressin.
• Inheritance of two mutant genes for the vasopressin
receptor (V2).
• Inheritance of two mutant genes for aquaporin-2.
Dr Gihan Gawish
The Kidney and Homeostasis
• The kidney is one of the major homeostatic devices of
the body.
• it removes normal components of the blood that are
present in greater-than-normal concentrations.
• When excess water, sodium ions, calcium ions,
potassium ions, and so on are present, the excess
quickly passes out in the urine.
• On the other hand, the kidneys step up their reclamation
of these same substances when they are present in the
blood in less-than-normal amounts.
• Thus the kidney continuously regulates the chemical
composition of the blood within narrow limits.
Dr Gihan Gawish
Hormones of the Kidneys
• The human kidney is also an endocrine
gland secreting two hormones:
• Erythropoietin (EPO)
• Calcitriol (1,25[OH]2 Vitamin D3), the
active form of vitamin D ( See the Chapter of bone)
• as well as the enzyme renin.
Dr Gihan Gawish
1. Erythropoietin Mechanism
Homeostasis: Normal blood oxygen levels
Increases O2-carrying ability
of blood
Reduces O2 levels in blood
Erythropoietin
stimulates red bone
marrow
Enhanced Erythropoiesis
increases RBC count
Dr Gihan Gawish
Kidney (and liver to a smaller
extent) releases erythropoietin
2. Role of Calcitriol
Dr Gihan Gawish
3. Regulation of Blood Pressure
by Hormones
• One of the functions of the kidney is to monitor
blood pressure and take corrective action if it
should drop. The kidney does this by secreting
the proteolytic enzyme renin.
• Renin acts on angiotensinogen, a plasma
peptide, splitting off a fragment containing 10
amino acids called angiotensin I.
• angiotensin I is cleaved by a peptidase secreted
by blood vessels called angiotensin converting
enzyme (ACE) — producing angiotensin II,
which contains 8 amino acids.
Dr Gihan Gawish
Regulation of Blood Pressure by
Hormones
Dr Gihan Gawish
Regulation of Blood Pressure by
Hormones
angiotensin II
• constricts the walls of arterioles closing down capillary beds;
• stimulates the proximal tubules in the kidney to reabsorb sodium
ions;
• stimulates the adrenal cortex to release aldosterone. Aldosterone
causes the kidneys to reclaim still more sodium and thus water
• increases the strength of the heartbeat;
• stimulates the pituitary to release the vasopressin.
• All of these actions, which are mediated by its binding to G-proteincoupled receptors on the target cells, lead to an increase in blood
pressure.
Dr Gihan Gawish
The Artificial Kidney
• The artificial kidney uses the principle of
dialysis to purify the blood of patients
whose own kidneys have failed.
Dr Gihan Gawish