RENAL PHYSIOLOGY

Dr. Mohammed Irfan

irfantpt@gmail.com
I. Physiological Anatomy of
the Kidney
 The two kidneys each weighing 150 gms in
adults are located retroperitoneally in the
upper dorsal region of the abdominal cavity
Shape bean shaped
10 cm 5 cm 2.5 cm
Human kidney

ureter renal artery

renal vein attached here

5
Gross Anatomy of the Kidney
 Aorta

Renal vein

Kidney

Renal artery

Vena cava

Ureter

Bladder

Urethra
Blood Supply to the Kidney
The renal artery --
segmental arteries --
interlobar arteries that
communicate with one
another via arcuate
arteries.
The arcuate arteries give
off branches called
interlobular arteries that
extend into the cortex.
Venous return of blood is
via similarly named veins.
Blood Supply to the Kidney
The interlobular arteries --
afferent arterioles --
glomerulus - efferent
arterioles --capillary
network surrounding the
tubule system of the
nephron.
The interlobular veins are
then the collecting vessel
of the nephron capillary
system.
Major Functions of the Kidneys
1. Regulation of:
body fluid osmolarity and volume
electrolyte balance
acid-base balance
blood pressure

2. Excretion of
metabolic products
foreign substances (pesticides, chemicals etc.)
excess substance (water, etc)

3. Secretion of
erythropoietin
1,25-dihydroxy vitamin D3 (vitamin D activation)
renin
prostaglandin
 1 Filtration by the Kidney
Supplied with blood
from renal artery
Renal
Lets have a look
artery at a nephron!!!
Inside it splits into
many fine capillaries
Renal
Each capillary supplies vein
blood to hundreds of
thousands of tiny
filtration units called
nephrons
Ureter
Nephron and
Collecting Duct
Nephron: The functional
unit of the kidney
Each kidney is made up of
about 1 million
nephrons
Each nephrons has two
major components:
1) A glomerulus
2) A long tube
Cortical nephron
Juxtamedullary
nephron
 branch of renal
glomerulus artery

Bowmans
capsule
DCT PCT

collecting
duct
branch of
renal vein
capillaries

loop 15
1. Glomerulus brings a large
surface area of blood capillaries
in close contact with Bowmans Blood from
capsule renal artery
enters wide
capillary
2. Liquid filtered from blood under
pressure (filtration)

3. Glomerular filtrate produced

Blood travels
containing:
through narrow
-water capillary
-glucose Filtration towards renal
-salts vein
-urea
Glomerular
filtrate
(Protein molecules and red blood
cells do not pass into tubule as
they are TOO BIG!!!!)
 Types of nephrons

Cortical nephron glomeruli in outer cortex & short

loops of Henle that extend only short distance into
medulla-- blood flow through cortex is rapid majority
of nephrons are cortical cortical interstitial fluid 300
mOsmolar
Juxtamedullary nephron glomeruli in inner part of
cortex & long loops of Henle which extend deeply
into medulla. blood flow through vasa recta in
medulla is slow medullary interstitial fluid is
hyperosmotic this nephron maintains osmolality in
addition to filtering blood and maintaining acid-base
balance
 The Renal Corpuscle
Composed of Glomerulus and Bowmans capsule
Renal tubules
and collecting
duct
 Key Words!!
Nephron: structure in the kidney that acts as
a microscopic filtration unit

Glomerulus: dense mass of very fine

blood capillaries at the
nephron that act as a filter

Bowmans capusle: cup-shaped part of the

nephron that holds a
glomerulus and collects the
products of filtration from it

Glomerular filtrate: liquid removed from the blood by

filtration in the kidney
overview of nephron function
 The juxtaglomerular apparatus
Including macula densa, extraglomerular mesangial cells, and juxtaglomerular (granular cells)
cells
 Juxta glomerular apparatus
JG cells- the JG cells are baroreceptors and
respond to changes in the transmural pressure
gradient between the afferent arteriole and
interstitium.
Macula densa cells- these are specialized renal
tubular epithelial cells located at the site
where thick segment of ascending limb of
loop of Henle is continued as DCT
 Mesangial cells or lacis cells- these are
supporting cells of JGA and found between
capillary loops. They are in contact with both
JG cells and the macula densa cells.
The JGA regulates the renin secretion into the
blood stream.
 Functions of the Nephron

Reabsorption Secretion

Excretion
Filtration
 Mechanism of formation of urine
Glomerular filtration rate
Definition- GFR refers to the volume of
glomerular filtrate formed each minute by all
the nephrons in both the kidneys.
Normal value 125 ml/min
180 L /day
 HUMAN RENAL PHYSIOLOGY
Four Main Processes:
Filtration

Reabsorbtion

Secretion

Excretion
 HUMAN RENAL PHYSIOLOGY
Functions of the Kidney:
Filtration:
First step in urine formation
Bulk transport of fluid from blood to
kidney tubule
Isosmotic filtrate
Blood cells and proteins dont filter

Result of hydraulic pressure

GFR = 180 L/day
 HUMAN RENAL PHYSIOLOGY
Functions of the Kidney:
Reabsorbtion:
Process of returning filtered material to
bloodstream
99% of what is filtered
May involve transport protein(s)
Normally glucose is totally reabsorbed
 HUMAN RENAL PHYSIOLOGY

Functions of the Kidney:

Secretion:
Material added to lumen of kidney from
blood
Active transport (usually) of toxins and
foreign substances
Saccharine
Penicillin
 HUMAN RENAL PHYSIOLOGY

Functions of the Kidney:

Excretion:
Loss of fluid from body in form of urine

Amount = Amount + Amount -- Amount

of Solute Filtered Secreted Reabsorbed
Excreted
Glomerular filtration
Occurs as fluids move
across the glomerular
capillary in response
to glomerular
hydrostatic pressure

blood enters glomerular capillary

filters out of renal corpuscle
large proteins and cells stay behind
everything else is filtered into nephron
glomerular filtrate
plasma like fluid in glomerulus
Factors that determining the
glomerular filterability
1.Molecular weight
2.Charges of the molecule
Starling Forces Involved in Filtration:

What forces favor/oppose filtration?

Glomerular Filtration

Figure 26.10a, b
 Glomerular filtration
Mechanism: Bulk flow
Direction of movement : From glomerular
capillaries to capsule space
Driving force: Pressure gradient (net filtration
pressure, NFP)
Types of pressure:
Favoring Force: Capillary Blood Pressure (BP),
Opposing Force: Blood colloid osmotic
pressure(COP) and Capsule Pressure (CP)
 Plasma is filtered through the
glomerular barrier
Components of plasma cross the three layers of the glomerular barrier during filtration
Capillary endothelium
Basement membrane (net negative charge)
Epithelium of Bowmans Capsule (Podocytes filtration slits allow size <60kD)
The ability of a molecule to cross the membrane depends on size, charge, and shape
Glomerular filtrate therefore contains all molecules not contained by the glomerular
barrier - it is NOT URINE YET!
 Glomerular filtration rate (GFR)
Amount of filtrate produced in the kidneys
each minute. 125mL/min = 180L/day
Factors that alter filtration pressure change
GFR. These include:
Increased renal blood flow -- Increased GFR
Decreased plasma protein -- Increased GFR. Causes
edema.
Hemorrhage -- Decreased capillary BP -- Decreased
GFR
Oncotic pressure
Oncotic pressure is the component of
total osmotic pressure due to colloid
particles.

Water molecules cross the membrane to

equalize the concentration of colloid
particles on each side.
GFR regulation : Adjusting blood flow

GFR is regulated using three mechanisms

1. Renal Autoregulation
2. Neural regulation
3. Hormonal regulation
All three mechanism adjust renal blood
pressure and resulting blood flow
1) Myogenic
Mechanism of the
autoregulation
Blood Flow = Capillary
Pressure / Flow
resistance
2) Tubuloglomerular feedback

2934
 2. Neural regulation of GFR

Sympathetic nerve fibers innervate afferent and

efferent arteriole
Normally sympathetic stimulation is low but can
increase during hemorrhage and exercise
Vasoconstriction occurs as a result which
conserves blood volume(hemorrhage)and
permits greater blood flow to other body
parts(exercise)
 3. Hormonal regulation of GFR
Several hormones contribute to GFR regulation
Angiotensin II. Produced by Renin, released by
JGA cells is a potent vasoconstrictor. Reduces
GFR
ANP(released by atria when stretched) increases
GFR by increasing capillary surface area available
for filtration
NO
Endothelin
Prostaglandin E2
 Measuring GFR
125ml of plasma is cleared/min in glomerulus(or
180L/day)
If a substance is filtered but neither reabsorbed
nor secreted, then the amount present in urine is
its plasma clearance(amount in plasma
cleared/min by glomerulus)
GFR = UV / P
U conc of inulin in urine- v volume of urine
P plasma inulin conc.
 Qualities of agents to measure GFR
Inulin: (Polysaccharide from Dahalia plant)
Freely filterable at glomerulus
Does not bind to plasma proteins
Biologically inert
Non-toxic, neither synthesized nor metabolized in
kidney
Neither absorbed nor secreted
Does not alter renal function
Can be accurately quantified
Low concentrations are enough (10-20 mg/100 ml
plasma)
 Qualities of agents to measure GFR

Creatinine:
End product of muscle creatine metabolism
Used in clinical setting to measure GFR but less
accurate than inulin method
Small amount secrete from the tubule
Section 3
Reabsorption and Secretion

Concept of Reabsorption and Secretion

 More water
reabsorbed

Glucose
reabsorbed Final urine
containing:
-excess water
-unneeded salts
-waste urea

Variable amounts of water and

salts reabsorbed and filtrate
gradually turning into urine
GFR 125 ml/min (180L/day)
(about 1% is excreted)
Filtration, reabsoption, and excretion rates of substances by the kidneys

Filtered Reabsorbed Excreted Reabsorbed

(meq/24h) (meq/24h) (meq/24h) (%)

Glucose (g/day) 180 180 0 100

Bicarbonate (meq/day) 4,320 4,318 2 > 99.9

Sodium (meq/day) 25,560 25,410 150 99.4
Chloride (meq/day) 19,440 19,260 180 99.1
Water (l/day) 169 167.5 1.5 99.1
Urea (g/day) 48 24 24 50
Creatinine (g/day) 1.8 0 1.8 0
 Think.
Which three components of the glomerular
filtrate are reabsorbed?

Why is it important for these to be

reabsorbed?

Which substances are present in the final

urine?
Two pathways of the absorption:

Transcellular
Lumen Pathway

Cells

Paracellular
transport
Plasma
Mechanism of Transport

1, Primary Active Transport

2, Secondary Active Transport

3, Pinocytosis

4, Passive Transport
Primary Active Transport
 Secondary active
Tubular Tubular Cell
transport
Interstitial Tubular
Tubular Cell
Interstitial

Fluid lumen Fluid

lumen co-transport counter-transport
(symport) (antiport)

out in out in

Na+ Na+

glucose H+

Co-transporters will move one moiety, e.g. Counter-transporters will move one moiety,
glucose, in the same direction as the Na+. e.g. H+, in the opposite direction to the
Na+.
Pinocytosis:
Some parts of the tubule, especially the
proximal tubule, reabsorb large molecules
such as proteins by pinocytosis.
 Passive Transport
Diffusion
1. Transportation of Sodium, Water and
Chloride
(1)Sodium, water and chloride reabsorption in
proximal tubule
Proximal tubule, including the proximal convoluted
tubule and thick ascending segment of the loop
Reabsorb about 65 percent of the filtered sodium, chloride, bicarbonate, and potassium and
essentially all the filtered glucose and amino acids.

Secrete organic acids, bases, and hydrogen ions into the tubular lumen.
 Sodium, water and chloride reabsorption in
proximal tubule

The sodium-potassium ATPase: major force for reabsorption

of sodium, chloride and water
In the first half of the proximal tubule, sodium is reabsorbed
by co-transport along with glucose, amino acids, and other
solutes.
In the second half of the proximal tubule, sodium reabsorbed
mainly with chloride ions.
 Sodium, water and chloride reabsorption in
proximal tubule

The second half of the proximal tubule has a relatively high

concentration of chloride (around 140mEq/L) compared with
the early proximal tubule (about 105 mEq/L)
In the second half of the proximal tubule, the higher chloride
concentration favors the diffusion of this ion from the tubule
lumen through the intercellular junctions into the renal
interstitial fluid.
(2) Sodium and water transport in the loop
of Henle

The loop of Henle consists of three functionally

distinct segments:

the thin descending segment,

the thin ascending segment,

and the thick ascending segment.

 Loop of henle ascending limb

Impermeable to water, permeable for salts.

Actively pumps sodium out of the filtrate,
generating the hypertonic interstitium that
drives countercurrent exchange.
Results in hypotonic solution in tubuli.
This hypotonic filtrate is passed to the distal
convoluted tubule in the renal cortex.
High permeable to water and
moderately permeable to most
solutes

but has few mitochondria and little

or no active reabsorption.

Reabsorbs about 25% of the filtered

loads of sodium, chloride, and
potassium, as well as large amounts
of calcium, bicarbonate, and
magnesium.

This segment also secretes hydrogen

ions into the tubule
Mechanism
of sodium,
chloride, and
potassium
transport in
the thick
ascending
loop of Henle
2. Glucose Reabsorption
Glucose is reabsorbed along with Na+ in the early
portion of the proximal tubule.

Glucose is typical of substances removed from the

urine by secondary active transport.

Essentially all of the glucose is reabsorbed, and no

more than a few milligrams appear in the urine per 24
hours.
The amount reabsorbed is proportionate to the
amount filtered and hence to the plasma glucose level
(PG) times the GFR up to the transport maximum
(TmG);
But when the TmG is exceed, the amount of glucose in
the urine rises
The TmG is about 375 mg/min in men and 300
mg/min in women.
The renal threshold for glucose is the plasma level at
which the glucose first appears in the urine.

One would predict that the renal threshold would be

about 300 mg/dl ie, 375 mg/min (TmG) divided by
125 mL/min (GFR).

However, the actual renal threshold is about 200

mg/dL of arterial plasma, which corresponds to a
venous level of about 180 mg/dL.
3. Hydrogen Secretion and Bicarbonate
Reabsorption.

(1)Hydrogen secretion through secondary Active

Transport.

Mainly at the proximal tubules, loop of Henle, and

early distal tubule ;

More than 90 percent of the bicarbonate is

reabsorbed (passively ) in this manner .
Secondary Active Transport
(2) Primary Active Transport
Beginning in the late distal tubules and continuing
through the reminder of the tubular system
It occurs at the luminal membrane of the tubular cell
Hydrogen ions are transported directly by a specific
protein, a hydrogen-transporting ATPase (proton
pump).
Primary Active Transport
Hydrogen Secretionthrough proton pump:
accounts for only about 5 percent of the total
hydrogen ion secreted

Important in forming a maximally acidic urine.

Hydrogen ion concentration can be increased as much

as 900-fold in the collecting tubules.

Decreases the pH of the tubular fluid to about 4.5,

which is the lower limit of pH that can be achieved in
normal kidneys.
4. Excretion of Excess Hydrogen Ions and
Generation of New Bicarbonate by the
Ammonia Buffer System
Production and secretion of ammonium
ion (NH4+) by proximal tubular cells.
For each molecule of glutamine metabolized in the
proximal tubules, two NH4+ ions are secreted into the
urine and two HCO3- ions are reabsorbed into the
blood.

The HCO3- generated by this process constitutes new

bicarbonate.
 Buffering of hydrogen ion secretion by
ammonia (NH3) in the collecting tubule.
Renal ammonium-ammonia buffer system is subject
to physiological control.

An increase in extracellular fluid hydrogen ion

concentration stimulates renal glutamine metabolism
and, therefore, increase the formation of NH4+ and
new bicarbonate to be used in hydrogen ion buffering;

a decrease in hydrogen ion concentration has the

opposite effect.
with chronic acidosis, the dominant mechanism by
which acid is eliminated of NH4+.
This also provides the most important mechanism for
generating new bicarbonate during chronic acidosis.
5. Potassium reabsorption and secretion
Mechanisms of potassium secretion and sodium reabsorption
by the principle cells of the late distal and collecting tubules.
6. Control of Calcium Excretion by the Kidneys

(1) Calcium is both filtered and reabsorbed in the kidneys but

not secreted
(2) Only about 50 per cent of the plasma calcium is ionized,
with the remainder being bound to the plasma proteins.
(3) Calcium excretion is adjusted to meet the bodys needs.
(4) Parathyroid hormone (PTH) increases calcium reabsorption
in the thick ascending loop of Henle and distal tubules,
and reduces urinary excretion of calcium
 An
Overview
of Urine
Formatio
n
Section 4. Urine Concentration and Dilution
Importance:

When there is excess water in the body and body fluid

osmolarity is reduced, the kidney can excrete urine with an
osmolarity as low as 50 mOsm/liter, a concentration that is
only about one sixth the osmolarity of normal extracellular
fluid.

Conversely, when there is a deficient of water and

extracellular fluids osmolarity is high, the kidney can excrete
urine with a concentration of about 1200 to 1400 mOsm/liter.
 The basic requirements for forming a
concentrated or diluted urine

(1) the controlled secretion of antidiuretic hormone (ADH),

which regulates the permeability of the distal tubules and
collecting ducts to water;

(2) a high osmolarity of the renal medullary interstitial fluid,

which provides the osmotic gradient necessary for water
reabsorption to occur in the presence of high level of ADH.
I The Counter-Current Mechanism
Produces a Hyperosmotic Renal
Medullary Interstitium
Hyperosmotic Gradient in the Renal Medulla
Interstitium
Countercurrent Multiplication and
Concentration of Urine
Figure 26.13c
I.II. Counter-current Exchange in the Vasa
Recta Preserves Hyperosmolarity of the
Renal medulla
 Role of urea in concentrating urine
Urea very useful in concentrating urine.
High protein diet = more urea = more
concentrated urine.
Kidneys filter, reabsorb and secrete urea.
Urea excretion rises with increasing urinary
flow.
 Urea recycling

Urea toxic at high

levels, but can be useful
in small amounts.
Urea recycling causes
buildup of high [urea] in
inner medulla.
This helps create the
osmotic gradient at
loop of Henle so H2O
can be reabsorbed.
The vasa
recta trap
salt and urea
within the
interstitial
fluid but
transport
water out of
the renal
medulla
III. Role of the Distal Tubule and
Collecting Ducts in Forming
Concentrated or Diluted urine
The Effects of ADH on the distal collecting
duct and Collecting Ducts

Figure 26.15a, b
 The Role of ADH
There is a high osmolarity of the renal medullary interstitial
fluid, which provides the osmotic gradient necessary for
water reabsorption to occur.
Whether the water actually leaves the collecting duct (by
osmosis) is determined by the hormone ADH (anti-diuretic
hormone)
Osmoreceptors in the hypothalamus detect the low levels
of water (high osmolarity), so the hypothalamus sends an
impulse to the pituitary gland which releases ADH into the
bloodstream.
ADH makes the wall of the collecting duct more permeable
to water.
Therefore, when ADH is present more water is reabsorbed
and less is excreted.
Renin, Angiotensin, Aldosterone:
Regulation of Salt/Water Balance
 Formation of Water Pores:
Mechanism of Vasopressin Action
A Summary of Renal Function
 Solute Diuresis

= osmotic diuresis
large amounts of a poorly reabsorbed
solute such as glucose, mannitol, or urea
 Osmotic Diuresis
Normal person Mannitol Infusion
Normal Person Water Restricted
Water restricted

M Cortex
M
Na M M M
M
H2 0 Na Na
H2 0

H2 0 Na
H2 0
H2 0 M
H2 0
Na
Medulla
M
M
Na

Urine Flow Low Urine Flow High

Uosm 1200 Uosm 400
 Sodium Balance Is Controlled By Aldosterone

Aldosterone:

Steroid hormone
Synthesized in Adrenal Cortex
Causes reabsorbtion of Na+ in DCT & CD
Also, K+ secretion
 Effect of Aldeosterone:
The primary site of aldosterone action is on the
principal cells of the cortical collecting duct.
The net effect of aldosterone is to make the kidneys
retain Na+ and water reabsorption and K+ secretion.
The mechanism is by stimulating the Na+ - K+ ATPase
pump on the basolateral side of the cortical
collecting tubule membrane.
Aldosterone also increases the Na+ permeability of
the luminal side of the membrane.
 Acid-base Balance
The importance of pH control
The pH of the ECF remains between 7.35 and
7.45
If plasma levels fall below 7.35 (acidemia), acidosis
results
If plasma levels rise above 7.45 (alkalemia), alkalosis
results
Alteration outside these boundaries affects all body
systems e.g. can result in coma, cardiac failure, and
circulatory collapse
 Common Acids
Carbonic acid is most important factor affecting
pH of ECF
CO2 reacts with water to form carbonic acid
Inverse relationship between pH and concentration
of CO2
 Mechanisms of pH control
Buffer system consists of a weak acid and its
anion
Three major buffering systems:
Protein buffer system
Amino acid
Hemoglobin buffer system
H+ are buffered by hemoglobin
Carbonic acid-bicarbonate
Buffers changes caused by organic and fixed acids
 Maintenance of acid-base balance
Lungs help regulate pH through carbonic acid -
bicarbonate buffer system
Changing respiratory rates changes PCO2
Respiratory compensation
Kidneys help regulate pH through renal
compensation
 Urinary bladder

The urinary bladder is a hollow muscular organ

shaped like a balloon.
It is located in the pelvic fossa and held in place by
ligaments attached to the pelvic bones.
The bladder stores urine - up to 500 ml of urine
comfortably for 2 to 5 hours.
Sphincters (circular muscles) regulate the flow of
urine from the bladder.
Internal urethral sphincter = in the beginning of urethra
smooth muscle not under our voluntary control
External urethral sphincter = skeletal muscle we can
control it
 Urinary bladder

The detrusor muscle is a layer of the urinary

bladder wall, made up of smooth muscle
fibers arranged in inner and outer longitudinal
layers and a middle circular layer.
Contraction of the detrusor muscle causes
the bladder to expel urine through the
urethra.
Problems with this muscle can lead to
incontinence.
 The urethra has an excretory function in both sexes,
to pass urine to the outside, and also a reproductive
function in the male, as a passage for sperm.
The external urethral sphincter is a striated smooth
muscle that allows voluntary control over urination.
Urethral sphincters:
Internal
External
In males the internal and external urethral sphincters
are more powerful, able to retain urine for twice as
long as females
 Urination (micturition)

The process of disposing urine from the urinary

bladder through the urethra to the outside of the
body.
The process of urination is usually under voluntary
control.
Urinary incontinence is the inability to control
urination, and is more common in women than
men.
Urinary retention refers to the inability to urinate.
Enuresis nocturna = incontinence during the night
(effects of emotions).
 Micturition reflex

Activated when the urinary bladder wall is stretched; it results

in urination.
This reflex occurs in the spinal cord, specifically in the sacral
region that is modified by the higher centers in the brain: the
pons and cerebrum.
The presence of urine in the bladder stimulates the stretch
receptors, which produces action potential.
The action potentials are carried by sensory neurons to the
sacral segments of the spinal cord through the pelvic nerves,
the parasympathetic fibers carry the action potentials to the
urinary bladder in the pelvic nerves.
The pressure in the urinary bladder increases rapidly once its
volume exceeds approximately 400-500 ml.
Urine Micturition

stretch
stretch
receptors
receptors
 Urine transport, storage and elimination

collecting duct
minor calyx
major calyx
renal pelvis
ureter
 micturation reflex
Urine transport, storage and elimination
ureter
urinary bladder
sphincters (2)
urethra
urethral opening
1. stretch bladder
2. sense
3. stimulate muscle
4. relax sphincter(s)
 Case I

A 52 yo male is seen for a routine physical exam

for the first time in a few years. His physician
discovers that the patient has been feeling more
tired than usual for a while. He also complains
of increased thirst and hunger, and says that he
has to get up several times at night to urinate.
The lab measured a random blood glucose of 350
mg/dl, urine dipstick positive for glucose, and
urine albumin/creatinine of 40 mg/g.
 Case 1 - DMII
Diabetes mellitus type II (adult onset)
Diabetes from Greek words meaning "siphon" or
"run through; mellitus is Latin for sweet.
Saturation of glucose transporters results in
glucose in urine.
Glucose in urine results in osmotic diuresis.
Chronic hyperglycemia leads to microvascular
damage, including damage to glomerular capillary
wall, resulting in microalbuminuria.
 Case 2

A 39-yr-old male with AIDS was admitted with

nausea, vomiting, abdominal pain, light-
headedness on standing, and weight loss. During
hospitalization, the patient developed hypotonic
polyuria with urine volumes of 9L/day associated
with intense thirst.
serum Na - 149 mmol/L [136-145]
urine osmolality - 71 to 88 mmol/kg [100-1000]
 Case 2
A water restriction test was performed, in which the
patient was given about 450 ml of 3% saline IV over 2
hours.
serum osm - 306 mmol/kg [280-300]
urine osm - 102
urinary ADH - undetectable
MR imaging showed changes in the posterior pituitary.
In response to treatment with desmopressin (10 g twice
daily by nasal spray), urine volumes decreased to 23
liters per day. The patient later died of bowel perforation.
Autopsy showed evidence of damage to the posterior
pituitary caused by CMV infection.
Case 2 - Diabetes Insipidus

Inability to concentrate urine

despite high serum sodium and
osmolality. Results in large volume
of dilute urine.
Central
damage to the posterior pituitary
results in inadequate ADH
production
treatment is exogenous ADH
Nephrogenic
kidney unresponsive to ADH
can be hereditary or acquired (eg,
lithium therapy)
serum ADH is high
 Case 3
A 61 year old male presented with confusion and
seizures two days after starting a new medication
(citalopram, an antidepressant).
serum Na - 124 mmol/L [136145]
serum osmolarity - 263 mOsm/L [285295]
urine Na - 141 mEq/L [40-220]
urine osmolarity - 400 mosm/L [100-1000]
urine output - < 1L/day
The patient's serum sodium gradually normalized
after the medication was discontinued.
 Case 3 - SIADH
SIADH = syndrome of inappropriate antidiuretic
hormone secretion
Open channels in the collecting duct lead to
excessive water resorption and a dilutional
hyponatremia.
can be caused by brain injury, ectopic production
by tumors, various drugs, major surgery,
pulmonary diseases, exogenous ADH
Treatment includes water restriction and salt
administration
EDEMA FROM THE NEPHROTIC SYNDROME
 Renal Papillary Necrosis

Caused by non-steroidal anti-inflammatory

drugs phenacetin and acetaminophen.
Highest concentration of drugs are in the
renal papilla.
Prostaglandin hydroperoxidase is highest in
the medulla and is thought to metabolize
these drugs to reactive quinoneimines.
Assessment of Kidney Function:
Morphologic Evaluation
Urinalysis
Gross evaluation of the kidney at necropsy
Histopathology of the kidney
Electron microscopy of the kidney
Assessment of Kidney Function:
Urinalysis
Proteinuria - indicates glomerular damage
Glycosuria - indicates tubular damage
Urine volume and osmolarity
pH
Enzymes - indicates tubular damage
Microscopic examination - casts, crystals,
bacteria, etc.
Assessment of Kidney Function:
Blood Chemistries
Blood urea nitrogen (BUN)
Creatinine
Electrolytes - Ca, Mg, K, P
Glomerular filtration rate - determines the
clearance of inulin, creatinine and BUN
Renal clearance - measures the clearance of
p-aminohippuric acid by filtration and
secretion
 Changes with aging include:

Decline in the number of functional nephrons

Reduction of GFR
Reduced sensitivity to ADH
Problems with the micturition reflex
Is it Christmas yet...