Transcript Physiology of kidney. Uropoesis. Role of kidney in keeping

Role of kidneys in supporting
of homeostasis
Function of kidney
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1. Excretion of ending nitrogen metabolic products.
2. Excretion of strange substances.
3. Excretion of excess of organic and unorganic
substances, which get into organism with food and
formed in metabolic processes.
4. Supporting of osmotic pressure of blood in a constant
level.
5. Supporting ionic balance of organism.
6. Supporting of acid-base condition of organism.
7. Take part in blood circulations' regulation.
8. Development of biological active substances and
enzymes (bradikinine, prostaglandines, urokinase,
vitamine D3, erythropoietin, renin etc.).
9. Take place in regulation of blood circulation volume.
Juxtaglomerular Apparatus
(continued)
Insert fig. 17.25
PHYSIOLOGIC CONTROL OF GLOMERULAR
FILTRATION AND RENAL BLOOD FLOW
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The determinants of GFR that
are most variable and subject
to physiologic control include
the glomerular hydrostatic
pressure and the glomerular
capillary colloid osmotic
pressure.
These variables, in turn, are
influenced by the sympathetic
nervous system, hormones and
vasoactive substances that are
released in the kidneys and act
locally, and other feedback
controls that are intrinsic to the
kidneys.
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Increased angiotensin II levels that
occur with a low-sodium diet or
volume depretion help to preserve
GFR and to maintain a normal
excretion of metabolic waste
products, such as urea and
creatinine, that depend on
glomerular filtration for their
excretion.
Endothelial-Derived Nitric Oxide Decreases Renal
Vascular Resistance and Increases GFR
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A basal level of nitric oxide production
appears to be important for preventing
excessive vasoconstriction of the kidneys and
allowing them to excrete normal amounts of
sodium and water.
Administration of drugs that inhibit the
formation of nitric oxide increases renal
vascular resistance and decreases GFR and
urinary sodium excretion, eventually causing
high blood pressure.
URINE FORMATION
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The rates at which different substances are excreted in the
urine represent the sum of three renal processes, (1)
glomerular filtration, (2) reabsorption of substances from
the renal tubules into the blood, and (3) secretion of
substances from the blood into the renal tubules.
Expressed mathematically,
Urinary excretion rate = Filtration rate
- Reabsorption rate + Secretion rate
Three basic renal processes
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The substance is freely filtered but is also
partly reabsorbed from the tubules back into
the blood.
For each substance in the plasma, a particular
combination of filtration, reabsorption, and
secretion occurs. The rate at which the
substance is excreted in the urine depends on
the relative rates of these three basic renal
processes.
The three basic renal processes
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Glomerular filtration
Tubular reabsorption
Tubular secretion
GFR is very high: ~180l/day.
Lots of opportunity to precisely
regulate ECF composition and
get rid of unwanted
substances.
N.B. it is the ECF that is being
regulated, NOT the urine.
Role of effective filtration
pressure
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Effective filtration pressure = P glomerulus
blood - (P oncotic + P capsula) = 65 - (25+15)
= 25 mm Hg.
Glomerular filtration rate is the volume of
filtrate produced by both kidneys each
minute. Glomerular filtration rate in average
is 90-130 ml/(min x 1,73 m2).
Tubular reabsorption
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Tubular reabsorption may be active or
passive. In primary convoluted tubule
reabsorbted amino acids, glucose,
vitamins, proteins, microelements, 2/3
of water, unorganic salts, such as Na+,
K+, Ca++, Mg++, Cl-, HCO3-. It all
connect with sodium reabsorption
Na+, K+, and H+ Relationship
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Na+ reabsorption in
CD creates electrical
gradient for K+
secretion.
Plasma [K+] indirectly
affects [H+].
When extracellular
[H+] increases, H+
moves into the cell,
causing K+ to diffuse
into the ECF.
In severe acidosis, H+
is secreted at the
expense of K+.
Insert fig. 17.27
Determination of tubular
reabsorption level
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Reabsorption of water =
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[(speed of glomerular filtration - diuresis per
minute) / speed of glomerular filtration] x 100 %.
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At norm it equal 98-99 %.
Concentration of urine
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In loop enters urea, which is
isotonic according to intracellular
fluid. Water reabsorbed here by
help of countercurrent mechanism.
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This mechanism determined by
functional characteristic of kidneys:
1) if the loop of Henle in deep position
in medulla part it increase the osmotic
pressure of intracellular fluid;
2) ascending part is not so permeable to
water;
3) epithelium of ascending part by help
of active transport system take out
sodium and chloride ions.
Descending Limb LH
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Deeper regions of medulla
reach 1400 mOsm/L.
Impermeable to passive
diffusion of NaCl.
Permeable to H20.
Hypertonic interstitial fluid
causes H20 movement out
of the descending limb via
osmosis, and H20 enters
capillaries.
Fluid volume decreases in
tubule, causing higher
[Na+] in the ascending
limb.
Insert fig. 17.16
Countercurrent Multiplier System
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Multiplies the
[interstitial fluid] and
[descending limb
fluid].
Flow in opposite
directions in the
ascending and
descending limbs.
Close proximity of
the 2 limbs:
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Allows interaction.
Positive feedback.
Insert fig. 17.16
Vasa Recta
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Countercurrent
exchange.
Recycles NaCl in
medulla.
Transports H20 from
interstitial fluid.
Descending limb:
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Urea transporters.
Aquaporin proteins (H20
channels).
Ascending limb:
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Fenestrated capillaries.
Insert fig. 17.17
Vasa Recta
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(continued)
Vasa recta maintains hypertonicity by
countercurrent exchange.
NaCl and urea diffuse into descending limb and
diffuse back into medullary tissue fluid.
At each level of the medulla, [solute] is higher in
the ascending limb than in the interstitial fluid;
and higher in the interstitial fluid than in
descending vessels.
Walls are permeable to H20, NaCl and urea.
Colloid osmotic pressure in vasa recta >
interstitial fluid.
Osmolality of Different Regions
of the Kidney
Insert fig. 17.19
Urea
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Contributes to total
osmolality of
interstitial fluid.
Ascending limb LH
and terminal CD
are permeable to
urea.
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Terminal CD has
urea transporters.
Urea diffuses out
CD and into
ascending limb LH.
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Recycle urea.
Insert fig. 17.18
Collecting Duct
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Medullary area impermeable to high [NaCl]
that surrounds it.
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H20 is drawn out of the CD by osmosis.
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The walls of the CD are permeable to H20.
Rate of osmotic movement is determined by the #
of aquaporins in the cell membrane.
Permeable to H20 depends upon the presence
of ADH.
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When ADH binds to its membrane receptors on
CD, it acts via cAMP.
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Stimulates fusion of vesicles with plasma membrane.
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Incorporates water channels into plasma membrane.
Secretion
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Secretion of substances from the peritubular
capillaries into interstitial fluid.
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Then transported into lumen of tubule, and into the
urine.
Allows the kidneys to rapidly eliminate certain
potential toxins.
Proximal Tubule
Secretion
Insert fig. 17.13
Transport Process Affecting Renal
Clearance
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Ability of the kidneys to remove
molecules from plasma and excrete
those molecules in the urine.
If a substance is not reabsorbed or
secreted, then the amount excreted =
amount filtered.
Quantity excreted = V x U
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Quantity excreted = mg/min.
V = rate of urine formation.
U = inulin concentration in urine.
Secretion process
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a) Organic acids and bases (choline) (It
secretes by help of active mechanism.)
b) Potassium (Sodium can change on
H+ and K+ ions).
c) Ammonium (It secretes by help of
mechanism of anionic diffusion.)
K+ Secretion
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90% filtered K+ is reabsorbed in early part of
the nephron.
Secretion of K+ occurs in CD.
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Amount of K+ secreted depends upon:
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Amount of Na+ delivered to the region.
Amount of aldosterone secreted.
As Na+ is reabsorbed, lumen of tubule becomes
–charged.
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Potential difference drives secretion of K+ into tubule.
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Transport carriers for Na+ separate from transporters for K+.
Modulation of K+ secretion
Luminal factors
Stimulators
Inhibitors
 Flow rate
 [K+]
 [Na+]
 [Cl-]
 [Cl-]
 [Ca2+]
 [HCO3-]
Ba2+
-ve luminal voltage
Amiloride
Selected Diuretics
Peritubular Factors
Stimulators
Inhibitors
 K+ intake
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 [K+]
Adrenaline
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pH
Aldosterone
ADH
pH
K+ Secretion
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Final [K+]
controlled in CD
by aldosterone.
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When
aldosterone is
absent, no K+ is
excreted in the
urine.
High [K+] or low
[Na+] stimulates
the secretion of
aldosterone.
Only means by
which K+ is
secreted.
(continued)
Insert fig. 17.24
Effective kidney plasma flow =
(concentration of
paraaminohippuric acid in urine x
diuresis per minute) : concentration
of paraaminohippuric acid in
plasma
 Effective kidney blood flow =
Effective kidney plasma flow : (1 –
hematocrit).)
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Measurement of Renal Blood Flow
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Not all blood delivered to glomeruli is filtered
in the glomerular capsules.
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Most of glomerular blood passes to the efferent
arterioles.
20% renal plasma flow filtered.
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Substances are returned back to blood.
Substances in unfiltered blood must be
secreted into tubules to be cleared by active
transport (PAH).
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PAH can be used to measure renal plasma flow.
Measurement of Renal Blood Flow
(continued)
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Filtration and secretion clear only the
molecules dissolved in plasma.
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PAH clearance actually measures renal
plasma flow.
To convert to total renal blood flow, the
amount of blood occupied by
erythrocytes must be taken into account.
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Averages 625 ml/min.
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Foreign substances and drugs
are also poorly reabsorbed but,
in addition, are secreted from
the blood into the tubules, so
that their excretion rates are
high.
Excretion of Metabolic Waste Products, Foreign
Chemicals, Drugs, and Hormone Metabolites
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The kidneys are the primary means for eliminating waste
products of metabolism that are no longer needed by the
body. These products include urea (from the metabolism of
amino acids), creatinine (from muscle creatine), uric acid
(from nucleic acids), the end products of hemoglobin
breakdown (such as bilirubin), and metabolites of various
hormones.
These waste products must be eliminated from the body as
rapidly as they are produced. The kidneys also eliminate
most toxins and other foreign substances that are either
produced by the body or ingested, such as pesticides, drugs,
and food additives.
Regulation of Arterial Pressure
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In addition, the
kidneys contribute
to short-term
arterial pressure
regulation by
secreting vasoactive
factors or
substances, such as
renin, that lead to
formation of
vasoactive products
(for example,
angiotensin II).
The kidneys play a dominant role
in longterm regulation of arterial
pressure by excreting variable
amounts of sodium and water.