Information

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and Power point slides from lectures
• PP slides are in syllabus
• Send all class notes to Dr Wall who
will forward to lecturer
• Barry.Wall@va.gov
 Introduction
• Text: Renal Pathophysiology,
Helmut Rennke and Bradley Denker,
3rd edition, 2010
• Syllabus
• Small groups: Group Assignments:
attendance strongly encouraged
• Blackboard
 Examinations
• Exam questions come from both
small group sessions and lectures
• Lectures and slides follow textbook
 Role of the Kidney
Major function of kidney is to maintain
homeostasis for a number of solutes
and water

Homeostasis maintained despite

variations in endogenous production
and dietary intake
Homeostasis: maintaining total
body contents at a stable and
normal level, even in the face
of changes in dietary intake or
endogenous production rate.
 HOMEOSTASIS
• Electrolytes: sodium, potassium, chloride
• Water (osmolality)
• Acid-base: bicarbonate (ECFV buffer)
• Minerals: calcium, phosphorus,
magnesium
• Waste material: urea (protein), creatinine
(muscle), uric acid (nucleic acids)
 Endocrine Functions
• Erythropoietin
• 1-alpha hydroxylase to produce 1,25
(OH)2D3
• Renin
• Paracrine/autocrine functions
a. bradykinin
b. prostaglandin
c. endothelial factors
1. nitric oxide
2. endothelin
Blood pressure regulation: the kidney is the
critical organ in maintaining normal
blood pressure.
1) homeostasis of sodium and water,
maintaining normal extracellular fluid
volume.
2) control of the renin – angiotensin –
aldosterone axis.
3) production of vasodilatory substances
Other Functions of the Kidney
• Catabolism of small peptide hormones,
such as insulin (decreased nephron mass
therefore leads to decreased insulin
catabolism and resultant longer circulating
half-life of insulin)
• Kidney can produce glucose via
gluconeogenesis during fasting
• Kidney is responsible for elimination of
many medications, thus,changes in kidney
function will change plasma concentrations
of these drugs
 Concept of Balance
 Neutral balance refers to the state in which
dietary intake plus endogenous production
equals excretion rate of the kidney. In this
situation total body contents of the
substance remains stable
 Positive balance: intake plus endogenous
production >renal excretion rate, leading to
increased total body content
 Negative balance: intake plus endogenous
production <renal excretion rate, leading to
decreased total body content
 Mechanism of Kidney
Function
Glomerular level:
• massive quantities of plasma ultrafiltrate are
formed at the glomerulus (180 liters/d)
• this requires an enormous blood flow. ~10-20% of
total cardiac output
Tubular level:
• greater than 99% of glomerular filtrate must be
reabsorbed
• selective reabsorption and secretion determines
urinary excretion rates
• Glomerular and tubular levels must
operate in concert to achieve normal kidney
function (GFR).
• Glomerular filtration rate, therefore, is the
best index of overall kidney function.
•Other kidney functions correlate with GFR
Processes Involved in Renal Function
 Filtration
Deposition into Bowman’s space of an ultrafiltrate
of plasma from glomerular capillary blood
 Reabsorption
Transport of water and certain solutes from fluid
within the tubules into the peritubular capillaries
 Secretion
Addition of certain solutes (but not of water) to the
fluid in the tubules from the peritubular capillaries
 Excretion
Removal from the body of water and solutes as
urine
 Starling Forces
Promoting filtration out of capillary
1. hydrostatic pressure within capillary
2. oncotic pressure within interstitium
Opposing filtration out of capillary
3. oncotic pressure within capillary
4. hydrostatic pressure within interstitium
Net fluid flow in or out of capillary
Determined by the algebraic sum of the
Starling forces, and by the filtration
coefficient, Kf
Glomerular Filtrate Formation
• GFR = LpS (P - tau)
• Lp = capillary wall permeability
• S = glomerular capillary surface area
available for filtration
• P= hydrostatic pressure gradient between
capillary and Bowmans space
• tau = oncotic pressure gradient
between capillary and Bowmans space
 Ultrafiltration: Glomerular vs.
Other Capillaries
The glomerular system has:
• Higher hydrostatic pressure in capillary
and little decrease in this pressure along
the capillary
• Low hydrostatic pressure in Bowman’s
space (tubular reabsorption)
• Lower oncotic pressure in Bowman’s
space (protein-free ultrafiltrate)
• Higher Kf (permeability factor)
• Urine flow rate is not autoregulated
• Increased perfusion pressure results
in increased urinary flow rate
(pressure natriuresis)
• Urine flow rate is not a good index of
overall kidney function
• GFR is the best index of overall
kidney function
 Definitions
• Filtered load (mg/min) = (Px) x GFR
• Filtered load represents the amount of
substance in plasma that is filtered at the
glomerulus per unit of time
• Excretion rate (mg/min) = (Ux) x UFR
• Excretion rate represents the amount of
the substance excreted into the urine per
unit of time
• Urine flow rate is not autoregulated
• Increased perfusion pressure results
in increased urinary flow rate
(pressure natriuresis)
• Urine flow rate is not a good index of
overall kidney function
• GFR is the best index of overall
kidney function
Properties of Marker of GFR
• Present in plasma at a constant
concentration
• Freely filtered at the glomerulus
• Once filtered, no reabsorption,
secretion, synthesis, or
metabolism occurs
 GFR
• Exogenous example: inulin
• Endogenous example: creatinine (~10%
secretion, so over-estimates GFR)
• Given these properties, the filtered load of
inulin is equal to its excretion rate
• Pinulin x GFR = Uinulin x UFR
• GFR (ml/min) = Uinulin x UFR/Pinulin
• GFR is the best overall index of kidney
function
 Renal Clearance
Renal clearance represents the volume
of plasma cleared of the substance via
elimination into the urine per unit of
time
Units = ml/min
 Renal Clearance
• Renal clearance = (Ux x UFR)/Px
(ml/min)
• The renal clearance (ml/min) of any
substance cleared by the kidney can be
defined as: (Clearance of substance x) =
(urine concentration of x) x (urine flow
rate)/plasma concentration of x
• “UV/P”
 Clearance Ratio
• Clearance ratio: defined as the
clearance of the particular substance
(Cx) divided by GFR

• (Cx/GFR)
 Clearance Ratio
• If clearance ratio =1.0, then the solute is
handled like inulin and its renal clearance
is equal to GFR
• If clearance ratio <1, then this solute is
filtered, but reabsorbed (eg, sodium)
• If clearance ratio >1, then the solute is
filtered, and it is actively secreted from the
peritubular capillaries into the tubular fluid
(eg, potassium)
 Clearance Ratio
(Cont’d)
• If clearance ratio is 0, then either the
solute is too large to be filtered
(protein) or it is filtered and 100%
reabsorbed (glucose and amino
acids)
 Renal Plasma Flow
• There is no endogenous substance that
can be used to estimate renal plasma flow
• Para-aminohippurate (PAH) is an
exogenous substance that is filtered and
actively secreted such that it is almost
completely extracted from the plasma in
one pass through the kidney
• The clearance of PAH, therefore, is equal
to renal plasma flow
 Filtration Fraction
• Normal GFR is approximately 120 ml/min
• Normal renal plasma flow is approximately
600 ml/min
• Filtration fraction (FF) represents the
fraction of renal plasma flow which
becomes GFR
• FF = GFR/RPF = 120/600 = 0.2
• Thus, about 20% of renal plasma flow
becomes GFR
Alterations in Filtration Fraction
Volume depletion results in reduced cardiac
output and reduced renal plasma flow.
Filtration fraction increases in order to maintain
GFR at a constant level. This autoregulatory
response involves a vasodilatation of the
afferent arteriole and vasoconstriction of the
efferent arteriole. The efferent circulation
exiting the glomerulus now has a significantly
reduced hydrostatic pressure and a markedly
increased oncotic pressure. These factors
augment reabsorption of solute and water in
the peritubular capillaries, thus helping
preserve volume status.
 Autoregulation
• Whenever autoregulation is
occurring, there is enhanced
proximal tubular reabsorption
• This limits delivery to the distal
nephron and favors NaCl and water
conservation
Alterations in Filtration Fraction
Volume expansion augments cardiac output
and increases renal plasma flow. Filtration
fraction decreases in order to maintain GFR
at a constant level. The efferent circulation
exiting the glomerulus has a higher than
normal hydrostatic pressure and less
increase in oncotic pressure. These factors
diminish reabsorption of solute and water in
the peritubular capillaries, thus, promoting
the excretion of the excess solute and water.
 Syllabus
• See Summary tables concerning
hormonal changes, hemodynamic
changes, renal tubular changes that
occur with alterations in extracellular
fluid volume
• See syllabus: diuretics