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Year Level 7 [Renal Module]
EDEMATOUS STATES
Rommel P. Tolentino, MD, FPCP, FPSN
OUTLINE:
I. EDEMA
A. Common Etiology of Clinical Edema
B. Pathophysiology of Edema Formation
C. Water Balance
II. BODY FLUID COMPARTMENTS
III. PATHOPHYSIOLOGY OF EDEMA FORMATION
IV. STARLING’S LAW
V. EDEMA FORMATION
A. Major Causes of Edema According to
Primary Mechanism
B. Clinical Manifestations and Diagnosis
C. Edema
VI. NEPHROTIC SYNDROME
A. Pathogenesis of Nephrotic Syndrome
B. Diagnosis of Nephrotic Syndrome
C. Causes of Nephrotic Syndrome
VII. CLINICAL FEATURES
A. Edema
B. Poor Nutrition
C. Kidney Failure
D. Blood Clots
E. Infections
VIII. GENERAL PRINCIPLES OF THERAPY
A. When must edema be treated?
B. What are the consequences of removal of edema
fluid?
C. How rapidly should edema fluid be removed?
IX. TREATMENT OF NEPHROTIC SYNDROME
A. Treatment of Specific Symptoms
B. Management of Intractable Edema
AUDIO
I.
EDEMA

Palpable swelling produced by expansion of the
interstitial fluid volume.

Anasarca- generalized edema
A.
B.
Common Etiology of Clinical Edema
 Heart Failure
 Cirrhosis of the Liver
 Kidney diseases (Nephrotic Syndrome)
 Localized edema
 Venous obstruction (deep vein thrombosis,
venous stasis)
 Acute left ventricular failure (venous
obstruction)
 Allergic reactions (e.g. laryngeal edema)
Pathophysiology of Edema Formation
Two basic steps:
1. Alteration in capillary hemodynamics (that
favors the movement of fluid from the
vascular space into the interstitium).
2. Retention of dietary or intravenously
administered sodium and water by the
kidneys.
Team 8 | Chua. Dela Cruz. Joaquin. Rayel. Redota. Uy.
August 10, 2010
C.
Water Balance

Water is lost in urine, feces, perspiration,
evaporation
from
skin
(insensible
perspiration), and from the lungs during
breathing.
Figure 1: Water Balance.
Water Output
o The route of water loss depends on
temperature, relative humidity, and
physical exercise.

Regulation of Water Output
o The distal convoluted tubules and
collecting ducts of the nephrons regulate
water output.
o Antidiuretic hormone from the posterior
pituitary causes a reduction in the
amount of water lost in the urine.
_________________________________________________

II.
BODY FLUID COMPARTMENTS
Intracellular fluid
compartment (ICF)
Extracellular fluid
compartment (ECF)
Figure 2. The Body Fluid Compartments: Intracellular
and Extracellular Fluid Compartments.
Page 1of 12
EDEMATOUS STATES
Year Level 7 [Renal Modiule]|August 10, 2010


The 60-40-20 Rule:
o 60 % of body weight is water
o 40% of body weight is intracellular fluids
o 20% of body weight is extracellular fluid
Water Balance
o 2/3 ICF, 1/3 ECF
o CF is twice the volume of ICF
o Some theories; ICF 55%, ECF 45%
Daily water intake is about 2.5 L a day.
WATER
(L)
PROTEIN
(kg)
Na
(mmol)
K
(mmol)
Total
body
45
6
2550
4560
ECF
15
0.3
2250
60
ICF
30
5.7
300
4500
Table 1. Composition of the Body Water. Values are
approximation for a 70-kg person. The amount of water
present depends on the mass of adipose tissue. There is a
large percentage of water in infants (70%) and smaller in
obese people, in females, and in the elderly, largely because
of a lower proportion of muscle vs. adipose tissue.

Water Balance
o Body water in Females 50%
o Body water in Males 60%
o Body water in Infants 70%
o Body water in elderly – small body water,
small muscle mass
COMPARTMENT
% BODY WEIGHT
VOLUME (L)
Body
60
45
ICF
40
30
ECF
Interstitial
Plasma
20
16
4
15
12
3
Blood
7
5
Table 2. Size of Various Body Fluids.
WATER
(L)
K
(mmol)
Na
(mm0l)
Muscle
22
3300
220
Brain,
liver, and
kidneys
2.5
375
25
Other
5.5
825
55
Team 8| Chua. Dela Cruz. Joaquin. Rayel. Redota. Uy.
Total
30
4500
300
Table 3. Distribution and Composition of the ICF.
COMPARTMENT
WATER
(L)
OTHER CONSTITUENTS
Total ECF
15
Contains 230 g albumin and
2250 mmol of Na
Interstitial
Volume
12
Contains
¼
of
the
concentration of albumin in
plasma, close to 50% of total
albumin
Plasma
Volume
3
Contains 120 g of albumin;
exists with 2L of red blood
cells in blood volume
Table 3. Distribution and Composition of the ECF.
_________________________________________________
III.
PATHOPHYSIOLOGY OF EDEMA FORMATION
Kidneys and Edema
 Clinical edema - increased interstitial volume of at
least 2.5 to 3 liters.
 Plasma volume - 3 liters
 Marked hemoconcentration and shock (if the
edema fluid were derived only from the plasma)
Figure 3. Capillary hemodynamics. When there is an
alteration in capillary hemodynamics, such as an elevated
capillary hydraulic pressure, that favors the movement of
fluid out of the vascular space into the interstitium.

Marked hemoconcentration and shock
o The initial movement of fluid from the
vascular space into the interstitium reduces
the plasma volume and consequently tissue
perfusion.
o Kidney retains sodium and water.
o Fluid stays in the vascular space, returning
the plasma volume toward normal.

Net Effect
Page2of 12
EDEMATOUS STATES
Year Level 7 [Renal Modiule]|August 10, 2010
o
Marked expansion of the total extracellular
volume (as edema) with maintenance of the
plasma volume at closer to normal levels.

Kidneys and Edema
o Renal Na and Water retention is an
appropriate compensation (in that it restores
tissue perfusion, even though it also
augments the degree of edema)
o Removing the edema fluid with diuretic
therapy will improve symptoms due to
edema (but may diminish tissue perfusion,
occasionally to clinically significant levels)
_________________________________________________
IV.
STARLING’S LAW
 Capillary hemodynamics
o Exchange of fluid between the plasma and the
interstitium is determined by the hydraulic
and oncotic pressures in each compartment.
 Relationship between hydraulic and oncotic
pressures:
 Net filtration =
LpS x (Δ HP Δ OP)
= LpS x [(Pcap-Pif)- s(Πcap-Πif)]
o Lp is the unit permeability (or porosity) of the
capillary wall
o S is the surface area available for fluid
movement
o Pcap and Pif are the capillary and interstitial
fluid hydraulic pressures
o Πcap and Πif are the capillary and interstitial
fluid oncotic pressures
o s represents the reflection coefficient of
proteins across the capillary wall (with values
ranging from 0 if completely permeable to 1 if
completely impermeable).

Starling's forces are substantially different in some
other organs.
o Skeletal muscles
o Liver sinusoids
o Alveolar capillaries
SKELETAL
ALVEOLI
MUSCLE
Hydraulic pressure
Capillary (mean)
17.3
8
Interstitium
-3.0
-2.0
Mean gradient
20.3
10
Capillary (mean)
28
26
Interstitium
8
18
Mean gradient
20
8
Oncotic pressure
Team 8| Chua. Dela Cruz. Joaquin. Rayel. Redota. Uy.
Net gradient favoring
filtration
0.3
2
Table 4. Starling’s Forces in Different Organs. Approximate
values for Starling's forces in skeletal muscle and alveoli.
Units are mmHg. The mean capillary oncotic pressure rises
in the glomerulus because of the filtration of relatively
protein-free fluid.

Capillary hydrostatic pressure, which pushes fluid
out of the capillary

Plasma oncotic pressure, which pulls fluid into the
vascular space

Fluid is returned to the systemic circulation by the
lymphatics to avoid edema.
_________________________________________________
V.
EDEMA FORMATION
 Alteration in one or more of Starling's forces (in a
direction that favors an increase in net filtration)
o Elevation in capillary hydraulic pressure
o Elevation in capillary permeability
o Elevation in interstitial oncotic pressure
o Reduction in the plasma oncotic pressure
A. Major Causes of Edema According to
Primary Mechanism
1. Increased capillary hydraulic pressure
 Increased plasma volume due to renal Na+
retention
o Heart failure, including cor pulmonale
o Primary renal sodium retention

Renal disease, including the
nephrotic syndrome

Drugs:
minoxidil,
diazoxide,
thiazolidinediones,
calcium
channel blockers (particularly
nifedipine), nonsteroidal antiinflammatory
drugs,
fludrocortisone, estrogens

Refeeding edema

Early hepatic cirrhosis
o Pregnancy and premenstrual edema
o Idiopathic edema, when diureticinduced
 Venous obstruction
o Cirrhosis or hepatic venous obstruction
o Acute pulmonary edema
o Local venous obstruction
 Decreased arteriolar resistance
o Calcium channel blockers (?)
o Idiopathic edema (?)
2. Decreased
plasma
oncotic
pressure
(Hypoalbuminemia= <1.5-2g/dl)
 Protein loss
o Nephrotic syndrome
o Protein-losing enteropathy
 Reduced albumin synthesis
o Liver disease
o Malnutrition
3. Increased capillary permeability
Page3of 12
EDEMATOUS STATES
Year Level 7 [Renal Modiule]|August 10, 2010







B.
C.
Idiopathic edema (?)
Burns
Trauma
Inflammation or sepsis
Allergic reactions, including certain forms
of angioedema
 Adult respiratory distress syndrome
 Diabetes mellitus
 Interleukin-2 therapy
 Malignant ascites
4. Lympathic obstruction or increased intersititial
oncotic pressure
 Postmastectomy
 Nodal enlargement due to malignancy
 Hypothyroidism
 Malignant ascites
5. Uncertain mechanism
 Docetaxel
 Pramipexole
Edema can also be induced by lymphatic
obstruction ---since the fluid that is normally
filtered is not returned to the systemic circulation.
Hypoalbuminemia
o Albumin loss in the urine in the nephrotic
syndrome
o Decreased hepatic albumin synthesis
Clinical Manifestations and Diagnosis
General Questions to ask
1. Is there a history of any disorder?
2. Where is the edema located?
3. Is the edema intermittent or persistent?
Edema is intermittent in pregnant women.
The physical examination can also aid in
establishing the proper diagnosis
 Pattern of distribution of edema, which
reflects those capillaries with altered
hemodynamic forces
The pattern of distribution would give us
an idea of the etiology.
 Central venous pressure
 Presence or absence of pulmonary edema
Edema
Pulmonary edema
 shortness of breath, orthopnea, chest pain (e.g
acute MI)
 PE: tachypneic, diaphoretic, wet rales, heart
murmurs and gallop rhythms
 Diagnosis: by chest x-ray (ddx: similar
symptom - pulmonary embolus
 Cause: cardiac disease, volume overload in
primary renal Na retention (Acute GN), or by
increased capillary permeability (ARDS)
 Pulmonary
capillary
wedge
pressure:
exceeding 18 to 20 mmHg (heart disease or
primary renal sodium retention) normal in
ARDS (unless there is concurrent heart disease
or fluid overload
 NOT associated with uncomplicated cirrhosis
Team 8| Chua. Dela Cruz. Joaquin. Rayel. Redota. Uy.
Pulmonary edema does not occur in
uncomplicated cirrhosis unless right-sided
heart failure sets in.
 Pulmonary edema does occur with
hypoalbuminemia
Pulmonary edema does not occur with
hypoalbuminemia unless you have a
kidney problem.
Peripheral edema and ascites
 Cosmetically undesirable but produce less
serious symptoms
 Swollen legs, difficulty in walking, increased
abdominal girth, and, in patients with tense
ascites, shortness of breath due to pressure on
the diaphragm.
 Presence of pitting after pressure is applied to
the edematous area.
 Located preferentially in the dependent areas,
it is primarily found in the lower extremities in
ambulatory patients and over the sacrum in
patients at bed rest.
 Nonpitting
edema
suggests lymphatic
obstruction or thyroid disease
 Grading of pitting edema from 1+ to 4+ (mild
to severe)
 Since the degree of edema is also influenced
by posture, documenting weight loss is
another component of monitoring the efficacy
of diuretic therapy.
Ascites
 Associated with abdominal distention and
both shifting dullness and a fluid wave on
percussion of the abdomen.
 Nephrotic syndrome, may also have
prominent periorbital edema due to the low
tissue pressure in this area.
_________________________________________________
VI.
NEPHROTIC SYNDROME
 Refers to a group of signs and symptoms that
occur in people with kidney (renal) disease.
 May occur in association with a variety of kidney
diseases as well as other diseases, such as
diabetes mellitus
 Defined by the presence of:
o Significant proteinuria
 high levels of protein in the urine
o Hypoalbuminemia
 low levels of the protein albumin in the
blood
o Peripheral edema
 swelling of the legs and ankles due to the
abnormal
collection of fluids in the
tissues
o Hyperlipidemia
 high blood cholesterol levels
o Thrombotic disease
Page4of 12
EDEMATOUS STATES
Year Level 7 [Renal Modiule]|August 10, 2010

A.
blood clots in the veins and arteries --- are
also common in people with nephrotic
syndrome.
Pathogenesis of Nephrotic Syndrome
 Results from damage to the glomeruli, the
structures in the kidneys that work to filter the
blood
 This damage permits proteins in the blood to
leak into the urine, causing proteinuria.
 Due to changes in normal kidney function, low
blood levels of albumin and edema eventually
result.
Figure 4. Increased collecting tubule sodium reabsorption in
nephritic syndrome. Micropuncture studies (in which
samples are taken via micropipettes from different nephron
segments) of sodium handling in unilateral nephrotic
syndrome in the rat. Although less sodium is filtered in the
nephrotic kidney, less is reabsorbed so that the quantity of
sodium remaining in the tubular lumen at the end of the
distal tubule is the same in the two kidneys. Thus, sodium
reabsorption must be increased in the collecting tubules to
account for the two-thirds reduction in total sodium
excretion in the nephrotic kidney when compared to the
normal kidney.
Figure 5. Plasma albumin in nephritic syndrome and CAPD.
Relationship between total albumin loss and the plasma
albumin concentration in patients undergoing continuous
ambulatory peritoneal dialysis (CAPD), in which albumin is
primarily lost in the dialysate fluid, and those with the
Team 8| Chua. Dela Cruz. Joaquin. Rayel. Redota. Uy.
nephrotic syndrome. At any level of albumin loss, the
plasma albumin concentration is approximately 1 g/dL (10
g/L) lower in patients with the nephrotic syndrome,
suggesting that some factor in addition to urinary albumin
excretion must be involved.
Figure 6. Little change in oncotic pressure grafient in
nephritic syndrome. Relation between plasma and
interstitial oncotic pressures in patients with the nephrotic
syndrome due to minimal change disease before (open
circles) and after (closed circles) steroid-induced remission
of the proteinuria. Both parameters are reduced in the
nephrotic state, resulting in little change in the
transcapillary oncotic pressure gradient and therefore little
tendency to promoting edema formation.
Figure 7. Volume regulatory hormones in glomerular
disease. Levels of plasma renin activity (ng/L per sec) and
atrial natriuretic peptide (fmol/mL) in normal subjects
ingesting 20 and 130 meq of sodium per day and in patients
with acute glomerulonephritis and nephrotic syndrome
excreting 25 meq of sodium per day. Patients with nephrotic
syndrome (fourth panel) show signs of renal sodium
retention since they have a hormonal profile similar to
those in normal subjects excreting 130 meq/day (second
panel) despite having a much lower rate of sodium
excretion. There is also evidence for a contribution from
underfilling as these patients do not have the profile of pure
volume expansion (very low renin, very high ANP) seen in
acute glomerulonephritis.
Page5of 12
EDEMATOUS STATES
Year Level 7 [Renal Modiule]|August 10, 2010
o Unexplained acute or subacute renal
B. Diagnosis of Nephrotic Syndrome

Laboratory Examination
1. Urine examination
 24 hour urine collection for protein
excretion
 Urine protein creatinine ratio (UPC)
o Normal value of protein in the
urine is less than 150 mg/day
o Heavy proteinuria (Nephroticrange) – more than 3 g/day
failure
Contraindications for Kidney Biopsy
o Patients in whom the biopsy, PE and lab
results strongly support a post-infectious
GN
o Uncorrectable bleeding problems
o Single functioning kidney
o Active renal infections
o Severe hypertension, before adequate BP
control
o Other concomitant problems (relative
contraindications), renal stones, renal
cysts, congenital malformations
Causes of Nephrotic Syndrome
 Etiology of Nephrotic Syndrome
o Minimal change disease
o Membranous nephropathy
o Focal glomerulosclerosis
o Diabetes mellitus
o Systemic lupus erythematosus

C.
Figure 8. Protein-creatinine ratio to estimate protein
excretion. This graph illustrates the close relation between
total daily urinary protein excretion and the total protein-tocreatinine ratio (mg/mg) determined on a random urine
specimen.
2.
3.
Blood test
 Creatinine, Blood Urea Nitrogen
 ANA, C3, ASO titer
 Albumin, Globulin, TPAG
 SGOT, SGPT, FBS, lipid profile
 Hepatitis profile
Kidney biopsy
 Percutaneous kidney biopsy
 Ultrasound guided
 Indications for Kidney Biopsy
o Nephrotic Syndrome
o AGN of undetermined etiology
o RPGN
o CGN of unknown duration with normal
sized kidneys
o Patients with SLE who develop proteinuria,
increased serum creatinine &/or active
urine sediments
o Patients with DM with features not typical
of DM nephropathy such as hematuria,
absence of associated retinopathy, short
duration DM
o Prospective
kidney
donors
with
asymptomatic urine abnormalities or
proteinuria
Team 8| Chua. Dela Cruz. Joaquin. Rayel. Redota. Uy.
Figure 9. Normal glomerulus on light microscopy.
Page6of 12
EDEMATOUS STATES
Year Level 7 [Renal Modiule]|August 10, 2010
Figure 10. Normal glomerulus on electron microscopy.
1.
Figure 11. Glomerulus with minimal change disease on light
microscopy.
Minimal Change Disease
 Nil disease or lipoid nephrosis - normal or very
mild abnormalities of the glomeruli
Changes can only be seen through electron
microscopy.
 90 percent of cases of nephrotic syndrome in
children under the age of 10
 More than 50 percent of cases in older
children
 In
adults:
use
of
nonsteroidal
antiinflammatory drugs (NSAIDs)
 Malignancy: Hodgkin lymphoma
Figure 12. Glomerulus with minimal change microscopy on
electron microscopy.
Team 8| Chua. Dela Cruz. Joaquin. Rayel. Redota. Uy.
Page7of 12
EDEMATOUS STATES
Year Level 7 [Renal Modiule]|August 10, 2010
Figure 13. Time course of natriuresis during recovery from
minimal change disease. Fractional excretion of sodium
(FENa, percent), plasma creatinine concentration (PCr,
mg/dL), plasma renin activity, and plasma albumin
concentration (PAlb, g/dL) in patients with minimal change
disease both before therapy and at the time of peak diuresis
during corticosteroid-induced remission. The FENa rose, in
association with reductions in the plasma creatinine
concentration and plasma renin activity, and a minimal
elevation in the plasma albumin concentration.
2.
Membranous Nephropathy
 Second most common cause of primary
nephrotic syndrome in adults
 Associated with hepatitis B infection
 Autoimmune diseases, thyroid disease, Use of
certain drugs
 Underlying cancer -- solid tumor
Figure 15. Glomerulus with membranous nephropathy on
light miscroscopy (silver stain).
Figure 16. Glomerulus with membranous nephropathy on
immunofluorescence microscopy.
Figure 14. Glomerulus with membranous nephropathy on
light microscopy.
Team 8| Chua. Dela Cruz. Joaquin. Rayel. Redota. Uy.
Page8of 12
EDEMATOUS STATES
Year Level 7 [Renal Modiule]|August 10, 2010



Present as a primary syndrome (primary FGS)
or may be associated with other conditions
(secondary FGS)
Causes collapse and scarring of some
glomeruli
Causes are unknown (in primary FGS), some
cases are the result of a genetic defect
Figure 17. Electron microscopy of a glomerulus with
membranous nephropathy showing subepithelial electron
dense deposits.
Figure 19. Glomerulus with mild focal glomerulosclerosis on
light microscopy.
Figure 18. Electron microscopy of a glomerulus with
membranous nephropathy showing a moth-eaten
appearance.
3.
Focal Glomerulosclerosis
 Most common cause of NS in adults, 35 % of
all cases, >50 % blacks
Team 8| Chua. Dela Cruz. Joaquin. Rayel. Redota. Uy.
Figure
20.
Glomerulus
with
moderate
glomerulosclerosis on light microscopy.
focal
Page9of 12
EDEMATOUS STATES
Year Level 7 [Renal Modiule]|August 10, 2010
Figure 22. Glomerulus with lupus nephritis on electron
microscopy.
_________________________________________________
Figure
21.
Glomerulus
with
collapsing
glomerulosclerosis on light microscopy.
focal
4.
Diabetes Mellitus
 Due to chronically elevated blood glucose
levels or hypertension
 More common among blacks, Mexicans, and
Pima Indians
 Risk of kidney disease is roughly equivalent in
both type 1 and type 2 diabetes
 Earliest sign is microalbuminuria (persistent
urine protein values between 30 and 300
mg/day)
 Many patients with this early sign develop
progressive kidney dysfunction, including
nephrotic syndrome.
5.
Lupus Nephritis

SLE is a chronic inflammatory disease of
unknown cause that can affect multiple
organs of the body, including the kidney.

Patients with SLE may develop nephrotic
syndrome due to a process similar to that of
membranous nephropathy.
Team 8| Chua. Dela Cruz. Joaquin. Rayel. Redota. Uy.
VII.
CLINICAL FEATURES
Table 5. Major Physical Findings in Edematous States.
A. Edema
 Periorbital edema
o Edema or swelling that affects the lining of
the eye socket, which is noticed after
waking in the morning.
 Pedal edema
o Swelling that occur in the feet after sitting
or standing for any period of time
B. Poor nutrition
 Weight loss occurs in patients with significant
proteinuria
o It may be hidden by increasing edema
Page10of 12
EDEMATOUS STATES
Year Level 7 [Renal Modiule]|August 10, 2010
 Worsened by appetite loss and vomiting
o Result of edema in the gastrointestinal
tract
Kidney failure
 Gradual decline in renal function
o No symptoms in the early stages
 Kidney failure can develop
o Fluid volume overload (cause shortness of
breath)
o Elevated blood potassium levels
o Hypertension (high blood pressure)
o Anemia (low red blood cell count)
o Bone disease
 Nephrotic syndrome, particularly in those who
have minimal change disease
 Due to several factors:
o Low blood volume
o Swelling of kidney tissues
o Injury to the tubules in the kidneys due to
lack of blood flow
o Use of nonsteroidal antiinflammatory
drugs
D. Blood clots
 Increased incidence (10-40% of patients) of
blood clots in the veins and arteries
(thromboemboli)
 Block blood flow– deep veins and renal veins
 Thrombosis of the renal vein is found most
commonly in patients with membranous
nephropathy.
o Present as sudden flank pain and blood in
the urine
o Or, much more commonly, develop slowly
over time and cause no symptoms
E. Infections

Patients with the nephrotic syndrome are
susceptible to infection

The body's normal defense mechanisms are
impaired with the nephrotic syndrome
_________________________________________________
C.
VIII. GENERAL PRINCIPLES OF THERAPY
 Treatment of edema consists of:
o Reversal of the underlying disorder (if
possible)
o Dietary sodium restriction (to minimize fluid
retention)
o Diuretic therapy
 Before initiating the use of diuretics, it is
important to consider the following
questions, which apply to all edematous
states:
 When must edema be treated?
 What are the consequences of the
removal of edema fluid?
 How rapidly should edema fluid be
removed?
Team 8| Chua. Dela Cruz. Joaquin. Rayel. Redota. Uy.
Loop diuretics are the most potent!
However, they usually do not work if the
patient has hypoalbuminemia.
A. When must edema be treated?
o Pulmonary edema
o Life-threatening
o Demands immediate treatment
o In all other edematous states --- SLOW
o True in cirrhosis in which hypokalemia,
metabolic alkalosis,
o Rapid fluid shifts induced by diuretics
can precipitate hepatic coma or the
hepatorenal syndrome
B. What are the consequences of the removal of
edema fluid?
 Retention of sodium and water by the kidney
o Compensatory act
o Heart failure, cirrhosis, and capillary leak
syndromes
o Raise the effective circulating volume
toward normal
 Fluid accumulation is inappropriate
o Primary renal sodium retention
o Effective circulating volume as well as the
total extracellular volume are expanded
 Removal of this fluid with diuretics
o Diminish the effective circulating volume
(When the retention of edema fluid is
compensatory)
o Fluid lost by diuresis comes from the
plasma volume (there will be a decrease in
venous return to the heart and therefore
in the cardiac filling pressure)
 Frank-Starling relationship
o Reduction in the left ventricular enddiastolic filling pressure (LVEDP)
o Lower the stroke volume in both normal
and failing hearts,
o Results in fall of cardiac output and
consequently in tissue perfusion
 Consequences
o Reduction in cardiac output (acute or
chronic heart failure), similar sequence can
occur in cirrhosis
o Increased secretion of the three
"hypovolemic" hormones (renin,
norepinephrine, and ADH)
o Decrease in the effective circulating
volume is sufficient to significantly impair
tissue perfusion
C. How rapidly should edema fluid be removed?
 EDEMA fluid can be mobilized rapidly
o Removal of 2 to 3 liters of edema fluid or
more in 24 hours can usually be
accomplished in patients with anasarca
without a clinically significant reduction in
plasma volume.
 EXCEPTION in cirrhosis and ascites but no
peripheral edema
Page11of 12
EDEMATOUS STATES
Year Level 7 [Renal Modiule]|August 10, 2010
o Excess ascitic fluid can only be mobilized
via the peritoneal capillaries.
o Direct measurements have indicated that
500 to 750 mL/day is the maximum level
that can be mobilized by most patients
 If the diuresis proceeds more rapidly
o Ascitic fluid will be unable to completely
replenish the plasma volume
o Azotemia and hepatorenal syndrome will
occur
_________________________________________________
IX.
TREATMENT OF NEPHROTIC SYNDROME
A. First line of treatment --- treat the underlying
disease that cause the nephrotic syndrome
B. Angiotensin converting enzyme (ACE) inhibitor
C. Diabetes mellitus
o Intensive management of blood glucose, lipids,
and blood pressure.
o Antihypertensive therapy, particularly ACE
inhibitors (frequently slows or even stops
disease progression)
D. Systemic lupus erythematosus
o Steroids and other immunosuppressive
medication
E. Minimal change disease
o Steroid therapy, other therapy in relapse
F. Membranous nephropathy
o Without treatment - spontaneous remission in
approximately 5 to 20 percent of cases and
partial remission in 25 to 40 percent of cases,
while 40 percent slowly lose renal function.
o Steroids and cytotoxic therapy
(immunosuppressive therapy) – benefits not
clear including survival.
A. Treatment of Specific Symptoms
 Treatment of Hypertension
o Objective BP=125/75mmHg or below for
patients with proteinuria >1g/day
o Encourage home BP monitoring inbetween clinic visits
o First line: ACE inhibitor unless
contraindicated
 Treatment of Hyperlipidemia
o Dietary instruction for low-fat diet
o Serum cholesterol monitoring every 2
months
o If serum cholesterol <200mg/dl --continue low fat diet alone
o Otherwise, start HMG CoA reductase
inhibitor (Statins)
 Dietary Protein Prescription
o Proteinuric patients with CrCl >/ 80ml/min
--- daily protein intake of 1g/kg/day of
mostly high biologic value protein
o <80ml/min --- 0.8g/kg/day
 Treatment of Hypervolemia
o Low salt diet and fluid restriction
Team 8| Chua. Dela Cruz. Joaquin. Rayel. Redota. Uy.
o Minimum furosemide dose of 40mg OD
B.
(normal serum creatinine), and 80mg OD
(elevated serum creatinine)
Management of Intractable Edema
G. Assess compliance
H. Reduce salt intake to <100meq/day (prep
<75meq/day
I. Assess need for vigorous diuresis and the
attendant risks
J. Discontinue, if possible, NSAID, phenytoin,
probenecid
K. Add or modify dose of diuretics
o Increase oral dose of loop diuretic until
maximum safe dose is achieved, increased
frequency of administration (if renal
function normal)
o IV diuretic (continous infusion for
hospitalized patients or those with GFR
<30-50ml/min
o Add distal-acting diuretic (intermittent or
daily), Metolazone 2.5-10mg/day or
Hydrochlorothiazide 50-100mg/day
o Add potassium-sparing diuretic if
hypokalemia is present or likely to develop
and GFR >30-50ml/min
L. Infuse salt-poor human serum albumin
o Premixed with an equimolar amount of
loop diuretic (e.g. 25g albumin + 150mg
furosemide infused over 1 to 4 hours)
M. Initiate extra-corporeal fluid removal
o (CAVH, hemodiafiltration) if anasarca is
debilitating
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