UNIT FOUR

 
ATERATION IN BODY FLUID

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Introduction

The health and well being of cells & tissues depend

not only on an intact circulation to deliver nutrients
but also on normal fluid haemostasis.

This chapter reviews the major disturbance involving

homodynamics and maintenance of blood flow

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Edema
 Definition:-

 excess fluid accumulation in interstitial tissue spaces.

 Excess fluid accumulation in the body cavities are designated as

 hydrothorax,
 Hydroperitoneum and
 Hydropericardium

 Definition of Terms

 Hydrothorax  excess fluid accumulation in Pleural Cavity

 Hydroperitoneum (Ascites)  excess fluid accumulation in

Peritoneal Cavity
 Hydropericardium excess fluid accumulation in Pericardial Cavity

 Anasarca  is a severe, generalized edema of the body with Profound

subcutaneous tissue swelling.

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Factors affecting fluid balance errors in
capillary & interstitial tissues
 Capillary hydrostatic (HP) & osmotic pressure (OP)
are normally balanced so that there is no net loss or
gain of fluid across capillary bed.
 An increased HP or diminished plasma OP leads to
a net accumulation of extra vascular fluid
(edema )
 As interstitial fluid Pressure increases, tissue
lymphatics remove much of the excess volume,
eventually returning to circulation
 If the ability of the lymphatics to drain tissue is
exceeded, persistent tissue edema results.
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Pathophysiologic Categories of edema
Is classified based on the causes of oedema
Increased hydrostatic Pressure

 Reduced Plasma oncotic Pressure

( Hypoproteinemia)
 Lymphatic obstruction

 Sodium retention ( with subsequent H2O

retention)
 Inflammation

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1. Causes of increased hydrostatic pressure
 Impaired (decreased) venous return
 CHF
 Constrictive Pericarditis
 (Ascites)  decreased vascular volume
 Venous obstruction or Compression
 Superior or inferior venacaval compression eg. by mass
(or any external Pressure )
 Thrombosis

 Arteriolar dilation
 Neurohumoral dysregulation

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2. Causes of Reduced Plasma osmotic Pressure (Hypo
proteinemia)
 Due to albumin loss or reduced albumin synthesis which is

important in maintaining plasma oncotic pressure

 Nephrotic syndrome (Protein- losing glomerular disease)
 Characterized by leaky glomerular capillary walls.
 Liver cirrhosis
 Malnutrition, malabsorption
 Protein losing gastropathy

 Therefore, reduced plasma oncotic Pressure leads to a net

movement of fluid into interstitial tissues and a resultant

plasma volume contraction (developing a vicious cycle)

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3. LYMPHATIC OBSTRUCTION

 Impaired lymphatic obstruction and consequent lymphoedema

 is usually localized.

 Causes
 Inflammatory

 Filariasis (Causes massive lymphatic & Lymph Node fibrosis in the inguinal
region).

 Edema of the genitalias & lower limbs (called elephantiasis).

 Neoplastic Obstruction

 Breast cancer (severe edema of the arm).

 Surgery & radiation to lymph nodes

 Causes localized edema eg. Surgery & irradiation to lymph nodes of breast leads to arm
edema.

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4. Sodium & H2O Retention

Retention of Na+ with subsequent H2O retention leads

to expansion of intravascular fluid volume which leads

to increased hydrostatic pressure.

Causes include:
Acute renal failure

Excess salt intake (Salt + H20) and IV fluids

Increased tubular reabsorb ion of Na+ due to increased

rennin- angiogenesis- aldosterone secretion.

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5. Inflammation
 Causes exudative oedema due to increased vascular permeability (Acute

or chronic inflammation).
 The edema fluid occurring in hydrodynamic derangement is typically a

protein- poor transudate, with a specific gravity of <1.012.

 Inflammatory oedema is a protein- rich exudates, with a specific gravity

usually over 1.020 due to increased vascular permeability.

Manifestations of oedema
 Any organ or tissue in the body may be involved.

 Common areas for oedema formation

 Subcutaneous tissues

 Lungs

 Brain

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1.Subcutaneous oedema can be
 i) Dependent oedema – on dependent parts of the body.

 Sacrum – recumbent
 Legs – standing
 Causes: CHF (congestive heart failure)
 ii) Non dependent – generalized

 e.g Renal failure, nephrotic syndrome cause generalized oedema

but initially manifest as periorbital swelling because of loose
connective tissue matrix.

2: Pulmonary oedema
 Occur usually in left ventricular failure

 May occur in adult respiratory distress syndrome (ARDS).

 lung ↑ 2.3x weight

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3: Oedema of the brain
may be localized at the site of lesion e.g. neoplasm,

trauma
may be generalized in encephalitis, hypertensive

crises& trauma
Narrowed sulci & distended gyri.

↑ Oedema → compression of medulla towards

foramen magnum → compression of vital center

lead to → herniation of the brain → Death

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Effects of oedema
 Effects of oedema may range from merely annoying to fatal.

 Subcutaneous tissue oedema

 in cardiac or renal failure is important primarily because it signals
underlying disease.

 Pulmonary oedema
 can cause death by interfering with normal ventilatory function.

 Brain oedema
 Serious and may be rapidly fatal

 If severe, brain substances can herniate through foramen magnum or the

brain stem vascular supply can be compressed which can injure the
medullary centre resulting in death.

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Clinical classification of oedema:

A) Localized B) Generalized

1) Deep venous thrombosis 1) Nephrotic syndrome

2) Pulmonary oedema2) Liver cirrhosis

3) Brain Oedema 3) Malnutrition

4) Lymphatic oedema 4) heart failure 5) Renal

failure

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 NEPHROTIC SYNDROMES:
 Non-inflammatory nephropathies.

 NEPHROSIS: Clinically characterized by

 proteinuria, loss of protein in the urine, usually due to

loss of negative charge, or holes, in the glomerular
basement membrane.
 Complications:
 Hypoalbuminemia
 Edema, resulting from hypoalbuminemia
 Hyperlipidemia, resulting from compensatory synthesis of
lipoproteins in liver.

 No hypertension.

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• Nephrotic Syndrome
a) massive proteinuria (> 3.5 g/day)
b) hypoalbuminemia
c) generalized edema
d) hyperlipidemia and lipiduria
Initial event is derangement of GBM → increasing permeability and
progressive loss of plasma proteins → hypoalbuminemia → decrease in
plasma colloid osmotic pressure → edema → ↓ plasma volume → ↑ aldosterone
→ ↓ ANP, GFR → ↑ water and solute retention by kidney → exacerbation of
edema (anasarca; massive amounts of edematous fluid); hypoalbuminemia →
↑ lipoprotein production by the liver
• In children < 15 yrs, nephrotic syndrome almost
always caused by primary renal disease (~ 98
%)
• In adults nephrotic syndrome may often be
associated with secondary renal disease

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 MINIMAL CHANGE DISEASE (Epithelial Cell Disease):

 Loss of negative charge on glomerular basement membrane, leading to

idiopathic proteinuria.
 PATHOGENESIS:
 Loss of negative charge on glomerular basement membrane
 leads to loss of epithelial foot-processes,
 which is only visible at the EM microscopic level.

 PATHOLOGY:
 The glomerulus appears histologically normal,
 but GBM appears flattened on EM.
 Size normally is not a barrier to the passage of albumin through the GBM.
 Normally negative charge is the only barrier.

 CLINICAL:
 The condition is not diagnosed until severe proteinuria (edema) occurs.

 TREATMENT:
 Treatment with corticosteroids is always quite successful

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 FOCAL SEGMENTAL GLOMERULOSCLEROSIS:

 An extension of Minimal Change Disease, with same basic pathology.

 PATHOGENESIS:

 Usually idiopathic, simply an extension of Minimal Change Disease with a worse

prognosis.
 But, it can be caused by HIV or heroin.

 PATHOLOGY:

 In addition to loss of negative charge and flattening of epithelial foot-processes,

we have:
 Glomerular Sclerosis: Some Glomeruli are fibrotic, sclerosed, or totally
obliterated. But, the damage is sparse:
 "FOCAL": Only some nephrons are affected, whereas others are spared.
 "SEGMENTAL": Only part of the glomerulus is affected. Half of the glomerulus
may appear normal.
 Hyalinosis: PAS-Positive material will appear in the affected glomeruli

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 DIABETIC GLOMERULOSCLEROSIS (Kimmelstiel-Wilson Disease):

 Negative charge on GBM can be lost in Diabetes, too.

 PATHOGENESIS:

 Proteinuria: Glycosylation of GBM proteins causes loss of charge on GBM

---> proteinuria.
 Progressive Renal Failure (lost filtration):
 Mesangial Matrix (kidney macrophages) builds up, and mesangial cells do not
turnover.
 Microangiopathy: Capillary lumen become compromised as a result of
mesangial cell buildup
 Hyaline Arteriosclerosis: Uniquely, both the afferent and efferent arterioles
can become atherosclerotic in Diabetes.

 PATHOLOGY:

 Thickened basement membrane.

 CLINICAL:

 Proteinuria occurs before renal failure. Hematuria is rarely or never seen.

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 Cirrhosis
 is diffuse fibrous scarring of liver due to hepatitis.

 Both alcoholic and viral hepatitis may end in Cirrhosis.

 Due to loss of architecture and necrosis there is liver

failure
 End result of many diseases of liver.

 Ethiology
 Alcoholic liver disease 60-70%
 Viral hepatitis 10%
 Biliary disease 5-10%

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  Primary hemochromatosis 5%
 Cryptogenic cirrhosis 10-15%
 Wilson’s, α 1AT def rare
 Pathogesis
 Hepatocyte injury & necrosis
 Fibrous scarring
 Parenchymal regeneration (non functional)
 Loss of archetecture & Vascular disruption
 Portal hypertension
 Liver failure – Hepatic coma

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 Complication

 Congestive splenomegaly.
 Bleeding varices.
 Hepatocellular failure.
 Hepatic encephalitis / hepatic coma.
 Hepatocellular carcinoma

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Normal liver
Micronodular cirrhosis

Marodular cirrhosis
Cirrhosis

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