
Glenda is a 48 year-old woman who presents to
you (her GP) saying that her legs have been
swollen for a month. On examination you find
that she has pitting oedema in both legs up to
her knees.

Q 1. How do you define oedema? Think of the
fluid compartments in the body, and what must
happen in order for oedema to develop, and try
to come up with the most basic explanation of
the development of oedema (one sentence.)

Definition of oedema:
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

palpable swelling produced by expansion of the interstitial
fluid volume (UptoDate)
An abnormal increase in interstitial fluid within tissues
(Robbins)
Development of oedema (UptoDate):


An alteration in capillary hemodynamics that favours the
movement of fluid from the vascular space into the interstitium
OR
The development of edema requires an alteration in one or
more of Starling's forces in a direction that favors an increase in
net filtration.
Revision slide

Starling forces determine fluid movement by osmosis
through capillary membranes:

1. Pc = capillary pressure––moves fluid out of capillary

2. Pi = interstitial fluid pressure––moves fluid into capillary

3. πc = plasma colloid osmotic pressure––moves fluid into
capillary

4. πi = interstitial fluid colloid osmotic pressure––moves
fluid out of capillary

Q 2. What four physiological processes affect trans-capillary
fluid exchange? Which of these are affected by chronic
kidney disease?
Overview

Edema––excess fluid outflow into interstitium commonly
caused by:

1. ↑ capillary pressure (↑ Pc; heart failure)

2. ↓ plasma proteins (↓ πc; nephrotic syndrome, liver failure)

3. ↑ capillary permeability (↑ Kf; toxins, infections, burns)

4. ↑ interstitial fluid colloid osmotic pressure (↑ πi;
lymphatic blockage)

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In more detail…
1.
Increased hydrostatic pressure –


Regional increases in hydrostatic pressure can result from a
focal impairment in venous return. Thus, deep venous
thrombosis in a lower extremity may cause localized edema in
the affected leg.
On the other hand, generalized increases in venous pressure,
with resulting systemic edema, occur most commonly in
congestive heart failure, where compromised right ventricular
function leads to pooling of blood on the venous side of the
circulation.
2.
Reduced plasma osmotic pressure occurs when albumin, the
major plasma protein, is not synthesized in adequate
amounts or is lost from the circulation. An important cause
of albumin loss is the nephrotic syndrome.


reduced plasma osmotic pressure leads to a net movement of
fluid into the interstitial tissues with subsequent plasma
volume contraction.
The reduced intravascular volume leads to decreased renal
perfusion  increased production of renin, angiotensin, and
aldosterone, but the resulting salt and water retention cannot
correct the plasma volume deficit because the primary defect of
low serum protein persists.
3.
Salt and water retention can also be a primary cause of
edema. Increased salt retention—with associated water—
causes both increased hydrostatic pressure (due to
intravascular fluid volume expansion) and diminished
vascular colloid osmotic pressure (due to dilution).

Salt retention occurs whenever renal function is compromised,
such as in primary disorders of the kidney and disorders that
decrease renal perfusion.
4.
Impaired lymphatic drainage results in lymphedema that is
typically localized; causes include chronic inflammation
with fibrosis, invasive malignant tumors, physical
disruption, radiation damage, and certain infectious agents.

Further examination findings are:



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T 37; BP 115/70; pulse 72 reg;
no abnormalities found on examination of the heart;
JVP not elevated;
peripheries are well perfused.
Abdominal examination is normal, as is the remainder of the
examination.
Urine dipstick shows protein 4+

Q 3. You consider that your patient has nephrotic syndrome,
on account of her heavy proteinuria and oedema. (i) What
quantity of protein in the urine constitutes ‘nephrotic range’
proteinuria? (ii) What is the third feature (in addition to
proteinuria and oedema) that makes up the classic triad of
nephrotic syndrome? (iii) what other classical features of the
syndrome will you seek?

What quantity of protein in the urine constitutes ‘nephrotic
range’ proteinuria?


3.5g/day
What is the third feature (in addition to proteinuria and
oedema) that makes up the classic triad of nephrotic
syndrome?


Hypoalbuminemia
Hyperlipidemia (Hyperlipidemia and lipiduria: An increase in
serum cholesterol and phospholipid levels and lipiduria are
typically components of the nephrotic syndrome. This is due to
increased hepatic synthesis, which may be triggered by the
decrease in plasma oncotic pressure)


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Proteinuria: due to increased permeability of the glomerular
basement membrane to albumin and arises in response to
alterations in both the size and charge barriers of the
glomerular filtration apparatus. Albumin is the predominant
protein excreted.
Hypoalbuminemia seems to be due to failure of hepatic
synthesis of albumin to compensate for the albumin lost in
urine. Release of cytokines may also suppress hepatic albumin
synthesis
Edema: Plasma oncotic pressure decreases because of
proteinuria and a decrease in serum albumin concentration.
What other classical features of the syndrome will you seek?

Hypertension, and hyponatremia

Other metabolic derangements:


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A hypercoagulable state, possibly due to urinary loss of
antithrombin III and decreased activity of proteins S and C.
Loss of vitamin D-binding globulin may result in vitamin D
deficiency, hypocalcemia, osteomalacia, and secondary
hyperparathyroidism.
Loss of immunoglobulins may result in impaired immunity
and increased rates of infections.

Causes:
Minimal change glomerulopathy



In children
Disease is immunologically mediated and related to abnormal
T-cell function rather than immune-complex deposition
Membranous nephropathy:


Most common clinicopathologic entity associated with
idiopathic nephrotic syndrome in adults
May be primary or secondary to a wide range of diseases. Its
pathogenesis is unknown, and treatment is controversial

Focal segmental glomerulosclerosis

Membranoproliferative glomerulonephritis
Secondary causes

Type 1 and 2 DM

SLE

Amyloid

Myeloma
Rare causes

Syphilis, sickle cell disease, Hep B, malaria, cancer, reflux
nephropathy, NSAIDs