Transcript Glomerular Filtration Rate (GFR)

Anatomy and Physiology
of the Kidney
Ali Abdi
Objectives
Brief review of renal anatomy
Explanation of kidney function
The 3 basic renal processes
Understand and explain renal physiology
 Glomerular filtration
 Tubular reabsorption
 Tubular secretion
( ‫آناتومی کلیه‬Kidney Anatomy)
Is about 10 cm long,
5.5 cm wide, and 3
cm thick & weighs
about 150 g
Internal Anatomy
Juxtaglomerular apparatus
At initial point of distal convoluted tubule
JG cells are present in the arteriole walls & act
as mechanoreceptors to sense BP in the
afferent arteriole
 JG cells are enlarged, smooth mm cells filled
w/secretory granules filled w/renin
Macula densa is a group of tall, packed cells in
the distal tubule & lies adjacent to the JG cells
 These are chemo/osmoreceptors that respond
to changes in solute content of the filtrate in the
lumen of the tubule
Structure of the Bowman’s (Glomerular)
Capsule
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Kidney physiology
 Account for ~0.5% of total body weight yet
consume 20-25% of all O2 used by the body at rest
 Process ~188 L (47 gallons) of blood derived
fluid/day
 Only ~1% of this (1.5 L) actually leaves the body as
urine
• 1000-1200 ml of blood/min pass through glomeruli
(650 ml of which is plasma)
• Equivalent to filtering your entire plasma volume
>60x/day
 Usually produce concentrated urine:
 1200–1400 mOsm/L (4 times plasma
concentration)
Functions of the kidneys
 Regulation of H2O and inorganic ion balance – most
important function!
 Removal of metabolic waste products from blood
and excretion in urine.
 Acid-base balance
 Removal of foreign chemicals in the blood (e.g.
drugs) and excretion in urine.
 Gluconeogenesis
 Endocrine functions (e.g. renin, erythropoetin, 1,25dihydroxyvitamin D)
The three basic renal processes
 Glomerular filtration
 Tubular reabsorption
 Tubular secretion
Nephron)‫(واحد عملکردی کلیه‬
 The functional unit of
kiney
 Kidneys contain 2.5
million Nephron
 Nephrons have two
functional component
one capillary system
and other tubular
system
THE NEPHRON
STRUCTURES OF THE NEPHRON
1. BOWMAN’S CAPSULE
2. PROXIMAL CONVOLUTED
TUBULE
3. LOOP OF HENLE
A. DESCENDING LIMB
B. ASCENDING LIMB
4. DISTAL CONVOLUTED TUBULE
THESE EMPTY INTO THE
COLLECTING
DUCT OR TUBULES.
Factors determining filtration
combination
Molecular size
Molecule charge
Molecules<20 Ao and without charge filtrated
easily
Molecules>40 Ao was not filtrated
20 Ao <molecules<40 Ao filtation is dependent
to their electrical charge
Albumin= 35.5 Ao and it is anion (negative
charge)
Glomerular filtration
 Mostly a passive process driven by hydrostatic Presure
 Glomerular filtration membrane is 1000s x more
permeable than regular capillary membranes
 Glomerular BP is higher than in other caps (55 mmHg
versus <18 mmHg)
 Kidneys produce ~ 180 L filtrate/day while other body
caps produce ~3-4 L/day combined
 Usually, molecules <3 nm (water, glucose, AAs,
nitrogenous wastes) can pass…molecules >7-9 nm are
usually completely barred from entering tubule
• Plasma proteins in the caps help maintain osmotic P
• proteins./RBCs in urine usually indicates a problem w/the
filtration membrane
Forces Involved in Glomerular Filtration
Glomerular Hydrostatic Pressure (GHP)
Is blood pressure in glomerular capillaries
Tends to push water and solute molecules:
 out of plasma & into the filtrate
Is significantly higher than capillary
pressures in systemic circuit:
 due to arrangement of vessels at glomerulus
Capsular Hydrostatic Pressure (CsHP)
Opposes glomerular hydrostatic pressure
Pushes water and solutes:
 out of filtrate & into plasma
Results from resistance to flow along nephron
and conducting system
Averages about 15 mm Hg
Blood Colloid Osmotic Pressure (BCOP)
Tends to draw water out of filtrate & into
plasma
Opposes filtration
Averages 25 mm Hg
Forces Involved in Glomerular Filtration
Glomerular filtration rate (GFR)
 The total amount of filtrate formed by the kidneys
per minute (avg. 125 ml/min)
 About 10% of fluid delivered to kidneys leaves
bloodstream & enters capsular spaces
 It is directly proportional to the net filtration
pressure
 Glomerular BP- (osmotic P of glomerular blood +
capsular hydrostatic P of other fluids in glomerulus)
 An increase in NFP (arterial BP) increases GFR &
vice versa (dehydration will increase glomerular
osmotic pressure & decrease GFR)
Glomerular Filtration Rate (GFR)
3 factors governing GFR at cap beds
1. Total surface area available for filtration
2. Filtration membrane permeability
3. Net filtration pressure
The normal GFR in both kidneys in adults is
~125 ml/min (7.5 L/hour..180 L/day)
3 controls of renal blood flow
These all function to keep
GFR at a fairly constant
level
1. Renal autoregulation
(intrinsic)
2. Renin-angiotensin
system (hormonal)
3. Neural controls (SNS)
Regulation of Filtration Pressure
Intrinsic controls (autoregulation)
 Maintains GFR despite changes in local blood
pressure and blood flow by changing diameters
of afferent arterioles, efferent arterioles, and
glomerular capillaries (Myogenic mechanism)
 Reduced blood flow or glomerular blood pressure
triggers:
 dilation of afferent arteriole, dilation of glomerular
capillaries, & constriction of efferent arterioles
 Rise in renal blood pressure:
 stretches walls of afferent arterioles, causes
smooth muscle cells to contract, constricts afferent
arterioles, & decreases glomerular blood flow
Intrinsic controls (autoregulation),
cont.
Tubuloglomerular feedback mechanism –
directed by macula densa of JGA
 Cells respond to high filtrate flow rate &
increased osmotic signals that leads to a release
of chemicals to cause severe vasoconstriction of
the afferent arterioles
 When macula densa cells are exposed to slowly
flowing filtrate or filtrate w/low osmolarity they
promote vasodilation of afferent arterioles
 Macula densa cells also send signals to JG cells
to set renin-angiotensin mechanism into motion
SNS control of GFR
SNS (+) causes vasoconstriction of afferent
arterioles & slows filtrate production
W/extreme stress or an emergency, the
autoregulatory mechanisms may be overcome
in order to shunt blood to vital areas like the
brain, skeletal mm, & heart at the expense of
the kidneys
 This also indirectly (+) the renin-angiotensin
mechanism by (+) the macula densa cells
 SNS can also directly (+) JG cells to release
renin by the binding of norepinephrin
Renin-angiotensin mechanism
Triggers of renin release
1. Reduced stretch of JG cells (hemorrhage,
salt depletion, deH2O)
2. JG cell (+) via macula densa cells
 promotes vasodilation of afferent
arterioles while simultaneously (+) JG
cells to vasoconstrict efferent arterioles
• 3. Direct (+) of JG cells via SNS fibers due
to decline in osmotic concentration of
tubular fluid at macula densa
Tubular reabsorption
Our total blood volume is filtered every 45
minutes so the majority of filtrate must be
reabsorbed & returned to the blood
Virtually all organic nutrients are reabsorbed
(glucose, AAs, etc)…kidneys function to
maintain or restore normal plasma levels
Reabsorption of H2O and many ions is
continuously monitored & adjusted in
response to hormonal signals
Reabsorption may be either active or passive
Tubular Reabsorption
Water: 99% reabsorbed
Sodium: 99.5% reabsorbed
Potassium: 86.1% reabsorbed
Calcium: 98.2% reabsorbed
Urea: 50% reabsorbed
Bicarbonat:99.9% reabsorbed
Glucose: 100% reabsorbed
Proximal convoluted tubule
The most active section for reabsorption
All glucose, lactate, & AAs
65% of Na in filtrate/~65 % of H2O
90% bicarb, 50% Cl, 55% K
Of the 125 ml/min of filtered fluid into the renal
tubules, ~40 ml remains to enter the loop of
Henle
Loop of Henle
Epithelium permeability changes
dramatically from PCT
For the first time, H2O reabsorption is not
coupled w/Na reabsorption
25%Na, 10%H2O, 35% Cl, 30% K
Distal convoluted tubule
Most reabsorption by this time is hormonally
regulated as the body needs
If necessary, nearly all H2O & Na reaching this
point can be reclaimed
 Reabsorption of the remaining Na is largely
dependent on aldosterone (causes collecting
ducts to become more permeable to Na)
w/o hormones, the DCT & collecting duct are
relatively impermeable to H2O
 Reabsorption is now dependent on ADH, which
makes the collecting ducts more permeable to
H2O
Secretion and Reabsorption
Tubular secretion
Essentially the reverse of tubular reabsorption
Blood entering peritubular capillaries:
 contains undesirable substances that did not
cross filtration membrane at glomerulus
More dominant in the PCT (& DCT/C.D.’s)
Important for:
 1. Disposing of substances not already in the
filtrate (i.e. certain drugs – penicillin)
 2. Elimination of certain undesirable endproducts reabsorbed by passive processes
(urea/uric acid)
 3. Ridding the body of excessive K ions
 4. Controlling blood pH
Thank You!