Update: February 24, 2002
Module C (III. and IVth year). Basic clinical problems
Course 8: Edema.
Summary of the syllabus:
 Disorders of water and sodium balance – Physiological and pathophysiological aspects
 Pathological anatomy of edema
 General principles of pharmacological treatment
 Clinical causes of edema
 Edema of cardiac and vessel origin
 Edema in renal diseases
 Edema in liver diseases
 Edema in connective tissue diseases
 Hormon induced edema and edema due to disorders of nutrition
 Edema in pregnancy
 Brain edema
 Upper airways edema
 Allergic edema
 Edema in burns
I.
Physiology and pathophysiology of edema / 4 hours
MUDr. Klára Bernášková
Disequilibrium of sodium and water metabolism.
* basic clinical terms.
a) distribution of body fluids into compartments
b) serum osmolality
distribution into intracellular and extracellular space
brain cells and extracellular space osmolality
c) osmotic gap
d) body fluid distribution into intravascular and extravascular space (Starling´s hypothesis)
* physiology and pathophysiology.
a) regulation of volume homeostasis
natriuresis and diuresis subject to blood pressure
effective circulating blood volume
renin-angiotensin-aldosterone system
sympathetic nervous system
atrial natriuretic factor (ANF, atriopeptide)
b) osmoregulation
adiuretin- vasopressin
concentration and dilution of urine in kidneys
c) integration of the various circuits and parameters of volume homeostasis
d) effect of hypernatremia and hyponatremia on the central nervous system
e) oedema formation
* clinical and pathogenetic aspects
a) overview of symptoms in disequilibrium of internal and external fluid homeostasis
b) oedema
types of oedema
c) internal fluid disbalance
hyponatremic syndrome
hypernatremic syndrome
II.
Pathological anatomy
MUDr. Jana Náprstková
* oedema of cardiac origin
* oedema of renal origin- in diseases characterised by the nephritic or nephrotic syndrome
* angioneurotic oedema
* lymphoedema
III.
Pharmacological treatment of oedema / 3 hours
MUDr. Jitka Patočková
Diuretic agents
- definition of the whole group,
- main principles in the mechanism of action
Classification of Diuretics :
- according to the mechanism of action
- according to the intensity of the diuretic effect
Main groups of diuretics :
1) Loop agents
main drugs : Furosemide, Ethacrynic acid
- mechanism of action (pharmacodynamics), basic pharmacocinetics
2) Thiazides
main drugs : Hydrochlorothiazide, Chlorothiazide, Chlortalidone
- mechanism of action (pharmacodynamics), basic pharmacocinetics
3) Potassium - sparing diuretics
main drugs : Spironolactone, Triamterene, Amiloride
- mechanism of action (pharmacodynamics), basic pharmacocinetics
4) Carbonic anhydrase inhibitors
main drugs : Acetazolamide
- mechanism of action (pharmacodynamics), basic pharmacocinetics
5) Agents enhancing primarily water excretion
main drugs : Osmotic diuretics (Mannitol), ADH Antagonists (Li salts, Tetracycline
derivates)
- mechanism of action (pharmacodynamics), basic pharmacocinetics
Mainly used combinations of diuretic agents :
loop diuretics + thiazides (acute therapy)
thiazides + potassium sparing diuretics (chronic therapy)
IV.
Causes of edema
Edema of cardiac and vessel origin
MUDr. Rudolf Špaček,CSc.
Edema is defined as a palpable swelling produced by expansion of the intersticial fluid volume. In the
development of cardiac edema and edema of vessel origin the rise of capillary hydraulic pressure play
the most important role. Increase of capillary pressure is a result of sodium retention and consequent
increase of plasmatic volume ( congestive heart failure and cor pulmonale ) or venous obstruction (
acute pulmonary edema, deep venous trombosis).
1. Congestive heart failure
Etiology
The prevalence of the clinical syndrome of congestive heart failure is about 2-9% and rapidly
incerases with age. The most common causes of systolic and diastolic heart failure are ischemic heart
disease ( 50% ), hypertension, cardiomyopathies and chronic lung diseases.
In forward heart failure the primary disorder is decreased cardiac index followed by decrease of
periferal tissue perfusion. The compensatory response is sympathetic - renin - angiotensin - aldosteron
system activation which tend to promote sodium and water retention and finally to edema.
Clinics
The main symptoms are induced by accumulation of fluid and decreased cardiac output. Increased
left ventricular end-diastolic and left atrial pressures are transmited back through the pulmonary veins
into the pulmonary capillaries. Pulmonary congestion leads to dyspnea, first on effort than paroxysmal
nocturnal and finally on rest. Typical physical finding are rales on the lung bases left ventricle dilatation,
S3, pulsus alternans or peripheral cyanosis. Symetrical pitting leg edema finally radiates proximally.
Usually there is also increase in jugular venous pressure, hepatomegally, fluidothorax and possibly
ascites or anasarca. Because of decrease of cardiac output patients suffer from weakness and fatigue.
The symphatetic stimulation leads to tachycardia and perspiration. Patients with coronary heart
disease may complain also of chest pain.
Diagnosis and assessement
Detailed history remain the mainstem approach to etiology and staging of heart failure. We are
interested about previous angina pectoris, hypertension, alcohol abuse, virosis, cardiac murmurs or
rheumatic fever. Chest X ray help us to distinguish between primary heart or lung disease. In heart
failure we find cardiothoracic index over 50% , signs of lung congestion or pleural effusion, mostly
rightsided. Cardiac shape is also typically changed in end-stage valvular disease. Normal ECG did not
support the diagnosis of systolic heart failure. The gold standard is echocardiographic assessement. It
gives informations about ejection fraction of the ventricles, presence of cardiac muscle hypertrophy,
pericardial effusion, structure and function of the cardiac valves. Doppler measurements have good
correlations with cardiac output, valve gradients, diastolic dysfunction or pulmonary hypertension.
Dobutamin echocardiography can discover ischemic dysfunction or presence of hibernating myocardial
muscle whose contractilily returns to normal after appropriate revascularisation. Coronary angiography
is indicated in all patients with new onset of heart failure especially if associated with chest pain.
Therapy
First choice therapy in patients with congestive heart failure are ACE inhibitors which can improve
short and long term survival and reduce morbidity. Diuretics remove excess of extracelullar fluid, relief
symptoms and improved quality of life. We usually start with low dose thiazid diuretic and finally switch
to loop diuretic or combination. Chronic use of ACEI prevent loss of potassium during diuretic therapy.
Symptomatic improvement can be achieved with digoxin and nitrates. In refractory edema especially in
patients waiting for heart transplantation arteriovenous hemofiltration or dialysis take place.
Prognosis
Patients may expirienced sudden cardiac death or can die for progresion of heart failure. The most
important predictors of death are LV ejection fraction < 20%, NYHA III-IV, VO2max < 10ml/kg/min,
high LVEDP, CI < 2l/min/m2, complex ventricular arrhythmias, increased concentration of
catecholamines and BNP.
2. Cor pulmonale
Etiology
This disorder is defined as a disturbance of structure and function of the right ventricle as a result of
precapillary pulmonary hypertension in chronic lung disease. The most common cause is chronic
obstructive lung disease (COLD ). Right ventricular failure may resulting in prominent edema in the
lower extremities and perhaps ascites. More often we find normal ejection fraction of the RV at rest
and even during exercise and normal glomerular filtration fraction. In these patients edema is a result
of hypercapnea, which leads to increased reabsoption of bicarbonates followed by pasive reabsorption
of sodium chloride and water in the kidney. Also chronic hypoxemia and consequent vasoconstriction
in renal vascular bed and reduction of sodium excretion play a role.
Clinics
Symptoms are nonspecific. Except of periferal edema we can find exertional dyspnea, fatigue,
cough, hemoptysis, chest pain or syncope. More severe RV failure may be associated with anorexia
and dyspeptic syndrome due to splanchnic congestion. Developement of ascites is not commmon
even in severe pulmonary hypertension.
Diagnosis
We use the same methods like in congestive heart failure. Other helpfull assessements are
spirometry and right side cardiac cathetrisation which can quantify pulmonary hypertension. In some
patients pulmonary biopsy may verify the etiology.
Therapy
In the most common form of the disease caused by COLD the basic is long term oxygenotherapy
which can decrease lung vasoconstriction and improve long term survival. Diuretics may improve
ejection fraction of both ventricles and remove edema. During chronic diuretic therapy it is
recommended to monitor plasmatic levels of kreatinin and urea to prevent excesive loss of
extracellural fluids. Developement of metabolic alcalosis and supression of breathing centre is another
possible complication of chronic diuretic therapy.
Prognosis
Moderate to severe pulmonary hypertension and peripheral edema is associated with bed prognosis.
These patients 5-year survival is about 30%.
3. Cardiac pulmonary edema
Etiology
The most common causes of systolic and diastolic LV dysfunction are ischemic heart disease,
hypertension, dilated cardiomyopathy, specific diseases of cardiac muscle and heart valvular disease.
Increased left ventricle filling enddiastolic pressure radiates backward into the pulmonary vascular bed.
As postcapillary pulmonary hypertension get more severe intracapillary pressure + intersticial oncotic
pressure overcomes intracapillary oncotic pressure. This leads to transsudation of the fluid first into the
lung intersticial space and than into the alveolar space. For limited period of time there is some
compensatory incerase in intersticial lymphatic drenage bud after that manifest pulmonary edema
appears.
Clinics
When the pulmonary capillary wedge pressure is over 25 mmHg plasmatic fluid soaks into lung
intersticial space which irritates J receptors and compress small bronchi. Main symptoms are dyspnea,
tachypnoe, orthopnoe, cough and protodiastolic gallop. Typical wet rales appears at the lung bases
during paroxysmal night dyspnea and also spastic fenomena are possible. Intraalveolar edema
appears when wedge pressure exceeded 35mmHg. Patient is in orthopnoic position, anxious, pale,
sweating and the sputum is pink foamed. Rales are accented and diffuse.
Diagnosis
We can use the same methods like in other disorders of cardiac origin. Right side cardiac
cathetrization help us to distinguish cardiac pulmonary edema from edema of noncardiac origin (
ARDS ) which is associated with normal pulmonary wedge pressure.
Therapy
Most effective is cause treatment of cardiac pulmonary edema i.e. early reperfusion in acute
myocardial infarction, rapid lowering of blood pressure in emergent hypertensive crisis, immediate
surgery in mechanical complicatin of AMI or elective surgery in valvular heart disease. Sometimes
therapy can be only symptomatic like at present in dilated cardiomyopathy. Supportive measures are
inhalation of 100% oxygen, assisted ventilation + PEEP, application of morphin or loop diuretic i.v. and
others. In patients with normal or elevated blood pressure use of i.v. nitroglycerin is indicated. In
hypotension we should use dopamin alone or in combination with dobutamine.
Prognosis
The prognosis of the patient with cardiac pulmonary edema depends on its etiology and treatment
possibility.
4. Local edema of vessel origin
Etiology
Most often is localized unilateral edema of one lower extremity due to deep vein system trombosis or
deep vein system valves inssuficiency in so called postphlebitic syndrome. Risc factors of deep vein
trombosis are age over 40, orthopedic or abdominal surgery, long time bed rest, malignant tumors,
congestive heart failure, obesity, varices and hemostatic disorders. Trombus formation leads to
increase of intracappilary hydraulic pressure folowed by transsudation of the fluid into intersticial space.
Less often edema may be of lymphatic origin due to decrease uptake of intersticial fluids. Lymphatic
vessels can be damaged in repeated inflammations, malignant blockade or congenitally.
Clinics
Edema is usually pale and painfull localized distally of the site of the trombosis. Colateral circulation
in superficial vein system is more prominent and painfull palpable resistence is present. During vein
slow flow the involved extremity can be cyanotic ( phlegmazia caerulea dolens ). In chronic vein
insuficiency except of edema also trofical changes like culf ulcer may be present. Other signs can be
nonspecific like increase in erythrocyte sedimentation, leucocytosis or subfebrile temperatures.
Diagnosis
Gold standard method is contrast venography. Most sensitive and specific noninvasive assessement
is ultrasonography with color wave Doppler mapping. Usefull may be also pletysmography and D-dimer
estimation which negative predictive value is about 99%. In diferencial diagnosis muscle contusion,
joint distorsion, edema associated with leg paresis or Baker cyst in gonartrosis must be consider.
Therapy
In the presence of deep vein trombosis appropriate anticoagulation is indicated. We can use
unfractioned heparin or LMWH and switch to Warfarin after relief of the symptoms. LMWH can be
used in uncomplicated outpatients.
Prognosis
Diseases associated with localized edema usually dont change the longevity unless pulmonary
embolization is not a complication.
Literature
I Málek, J Toman, M Štejfa
Doporučení pro diagnostiku a léčbu srdečního selhání
Cor Vasa 1998;40(1):K16-28
M Štejfa et al.
Kardiologie, Grada Publishing, s.r.o. 1995,s.557
J Widimský
Srdeční selhání, Triton, 1996,s.77
E Braunwald
Heart disease, 5th edition, 1997,s.1996
Edema in renal diseases
MUDr. Miroslava Horáčková, CSc.
Oedema in renal disease develops due to 2 different mechanisms:
* Primary oedema: retention of salt and water primarily by the kidneys (overflow theory). Suppression
of renin-angiotensin system activity, primary suppression of plasma renin and aldosterone.
* Secondary oedema: retention of salt and water by the kidneys as a consequence of adaptive
measures in decreased plasma volume and decreased effective circulating volume (underfill theory).
Plasma renin and aldosterone are elevated, the release of adiuretin- vasopressin is also increased.
Differential diagnosis.
1. nephropathy with primary oedema:
* some primary glomerulopathies with nephrotic syndrome
* acute glomerulonephritis
* nephropathy leading to acute renal failure
* nephropathy in end-stage chronic renal insufficiency.
2. nephropathy with secondary oedema:
* some glomerulopathies, including secondary types, with nephritic syndrome.
The nephrotic syndrome (NS)
Pathogenesis: injury to the glomerular membrane is always involved in the pathogenesis of this
syndrome. This injury leads to greater membrane permeability for plasma proteins. Adaptation events
lead to secondary oedema. In some patients with the NS, intra-renal factors that cause primary salt
and water retention (sustaining primary oedema formation) may be in play. Most probably, though, a
combination of both these factors leads to the development of oedema.
Clinical and laboratory findings: oedema generally involves the lower extremities in mobile patients and
the sacral region in bed-ridden ones. Oedema easily forms in areas with little fibrous tissue (periorbital
region, scrotum). In advanced disease, a hydroptic syndrome occurs with increased subcutaneous
oedema of the lower extremities and abdomen, the collection of fluid in the peritoneal, pleural and
pericardial space. In extreme cases, non-cardiac pulmonary oedema may develop. In some patients,
there are concurrent signs of effective circulating volume contraction (orthostatic hypotension,
orthostatic vertigo, tachycardia, increased sensitivity to diuretic administration- accentuation of the
pathological signs of effective circulating volume contraction).
Typical laboratory findings include: hypoproteinemia and hypoalbuminemia, dyslipoproteinemia,
(increased cholesterol plasma concentration), and hyperfibrinogenemia due to secondary increased
proteosynthesis in the liver, anaemia due to defective iron utilisation because of loss of transport
proteins, hypogammaglobulinemia due to renal losses of immunoglobulins. Normo/hyponatremia,
depending on the ECT/ICT state of equilibrium.
Diagnosis and differential diagnosis: NS develops following injury to the glomerular membrane due to
immunological and non-immunological insult. If the underlying cause is known (approx. 20% of cases)
then secondary NS is diagnosed. If the underlying injury is not known, the diagnosis of primary
(idiopathic) NS is made.
Examination: Oedema due to the NS is characterised by:
* hypoproteinemia, hypoalbuminemia, hypogammaglobulinemia, decreased antithrombin III
* hypercholesterolemia, prolonged prothrombin time (increased concentration of haemocoagulation
factors, fibrinogen!)
* hyponatremia (dilution) and hypokalemia (in secondary hyperaldosteronism).
Treatment: in secondary NS, one must consider removing the underlying cause of increased basal
membrane permeability. In most cases of NS only symptomatic treatment is possible- treating oedema
by pharmacological, and in exceptional circumstances, non-pharmacological means. Treatment of the
hypercoagulation syndrome. The effectiveness of statin administration in the treatment of attending
hypercholesterolemia depends on the stage of renal insufficiency.
Prognosis: in a small percentage of patients, the identification of underlying causes and their causal
treatment is possible. In most patients, though, this is not so and their prognosis is hence clear. In
some cases, immunosuppressive therapy may successful. This treatment, though, is attended by a
number of complications which, to a great extent, affect the prognosis of patients as well as their ability
to continue working.
Nephropathies accompanied by „primary oedema“
Pathogenesis renal retention of salt and water represents the key element in the etiopathogenetis.
Retention is caused by various mechanisms, depending on the underlying nephropathy.
Typical clinical and laboratory findings: the most significant clinical symptoms include hypertension
caused by extracellular compartment expansion, and left heart insufficiency or failure with pulmonary
oedema. Brain oedema with the development of neurological symptoms such as qualitative alterations
of the level of consciousness (amentia), seizures as well as quantitative alterations (coma) may also
occur. Patients often have oligo/anuria (decreased micturition).
Typical laboratory findings include hyperazotemia (elevated creatinine and BUN), especially in cases of
acute or end-stage chronic renal failure, and hyperuricemia. The extent of proteinuria depends on the
underlying nephropathy. The same applies to urinalysis findings. End-stage chronic renal failure is
characterised by anaemia, hypocalcemia, hyperphosphatemia, normo/hyponatremia (dilution), elevated
EFNa (relation between the amount of Na excreted and the glomerular filtration rate), hyperkalemia,
metabolic acidosis with anion gap.
Diagnosis and differential diagnosis: The main step in the differential diagnosis is distinguishing
between acute and end-stage chronic renal failure. The architecture and size of the kidneys on
ultrasound imaging, laboratory findings and special tests (special laboratory findings: ASLO, C3,C4,
ANCA, ANA, anti-dsDNA, anti-GBM, urine cytology, renal biopsy) in relation to the history and overall
clinical state may provide helpful clues.
Examination: Oedema and concurrent signs of extracellular volume expansion, oligo/anuria and
hyperazotemia should be categorised as possible causes of renal insufficiency (pre-renal/renal/postrenal), depending on laboratory tests and results of imaging methods (CAT, US).
Treatment: severe hyperazotemia, metabolic acidosis, hyperkalemia and hyperhydration together with
progression of pulmonary oedema and oligo/anuria require urgent treatment, regardless of their
aetiology. Such treatment , apart from conservative measures (salt and water replenishment in
accordance to hemodynamic parameters and diuresis, diuretics, urological invasive intervention)
consists of one of the haemo-purification methods. The choice of method depends on the technical
facilities available, the erudition of the medical staff involved and on individual choice, always keeping
in mind the constellation of laboratory findings and clinical signs and symptoms including
haemodynamic parameters (hemodialysis, CVVH, CVVHD).
Prognosis. Patient prognosis depends mainly on the presence or absence of chronic irreversible renal
failure. Most patients with chronic renal failure require one form of life-long kidney function replacement
(hemodialysis, peritoneal dialysis, transplant). Prognosis depends on the adaptation to this
replacement. This is given by the underlying nephropathy, multiple morbidity and age. Acute renal
failure need not always be a cause of permanent disability. Much depends on the aetiology,
possibilities of treating the underlying cause and other factors (age, multiple morbidity, complicationsfailure of other vital organs).
Idiopathic oedema.
Pathogenesis: there is no consensus on the cause of idiopathic oedema. It is possible that increased
capillary permeability, hyperaldosteronism, decreased effective circulating volume (especially when
trying to treat oedema with diuretics) and hyperprolactinemia may play a role.
Clinical and laboratory findings: women are practically always affected. They complain of generalised
oedema. oedema of the lower extremities, oedema of the fingers or of the palpebra. Sometimes the
oedema is cyclic and dependent on the phase of the menstruation cycle. Usually, there are
discrepancies between the objective findings and the intensity of patient complaints („true psychic
oedema“). Laboratory findings are non-specific.
Diagnosis and differential diagnosis. oedema caused by increased capillary hydraulic pressure and
oedema due to decreased colloid-osmotic pressure must be ruled out. Oedema due mainly to
increased capillary permeability is usually easy to distinguish (trauma, burns, inflammation, sepsis,
ARDS, treatment with interleukin-2). Allergic aetiology should be sought.
Treatment: pharmacological intervention is not possible. Diuretics aggravate symptoms and their
withdrawal leads to a marked rebound phenomenon with weight gain due to increased fluid retention.
This phenomenon often leads to dependency on diuretic treatment with all the negative consequences
this entails (pseudo-Bartter´s syndrome, kaliopenic nephropathy, severe hypokalemia with arrhythmia,
kaliopenic paralysis). Psychotherapy is recommended.
Prognosis: If no treatment with diuretics is attempted, the prognosis is good, and there is no change in
the patients ability to work. Incorrect treatment with diuretics and dependency on these drugs may lead
to serious complications including sudden death from malignant arrhythmia and the development of
renal insufficiency due to kaliopenic nephropathy.
Edema in liver diseases
MUDr. Blanka Cieslarová
Typical manifestation of edema in liver diseaseas is ascites. Ascites = fluid in abdominal cavity.
ETIOLOGY: combinations of some factors:
1. decrease of oncotical pressure - hypalbuminaemia
2. portal hypertension
3. lymphostasis
4. increase retention of water and natrium
5. decreased renal perfusion and redistribution of renal circulation
6. endocrinal changes - secondary hyperaldosteronism, elevated secretion of renin and ADH
7. elevated activity of sympathetic division
8. elevated concentration of prosthaglandins
PATHOGENESIS: 1.theory: primary are hemodynamic changes, when the renal blood flow is
decreased, renal cortex ischemia, impairing of renal functions, compensatory is elevated Na retention
to keep plasmatic volume, thus the complete vascular volume is elevated.
2. theory: primary portal hypertension with fluid accumulation in abdominal cavity decreases plasmatic
volume and sequential regulatory mechanisms elevate Na retention to “keep” plasmatic volume.
CLINICAL PICTURE: SUBJ: sensation of full abdomen, abdominal discomfort, flatulence (“ the wind
comes before the rain”), the thirst, sometimes edemas of legs, weight changes, breathing complaint.
OBJ.: fatigue appearance, dry skin and mucosa, enlarged abdominal volume, colateral circulation,
sometimes “ caput medusae”, or striae.
DIAGNOSIS:detection of ascites during physical examination is possible if there is about 2000ml of
fluid in abdominal cavity present ( positive undulation). Ultrasonography detects amount fluid of 200ml,
the same does CT examination and certainly laparoscopy. DIAGNOSTIC PUNCTURE: in each ascites.
In cirrhosis is ascitic fluid clear, or with yellow or green hue. The ascitic fluid is transudate ( specific
weight is 1018, lower content of protein: 10-20g/l). Rivalt test: positive in exudate, negative in
transudate. Sediment: in cirrhosis only solitary erytrocytes and leukocytes, total amount to 500/mm 3
DIFFERENTIAL DIAGNOSIS: 1. liver congestion ( right-side cardiac failure , constrictive pericarditis,
Budd-Chiarri syndrom) 2. infections ( bacterial, tbc, parazital, mycotic) 3. primary and secondary
tumors
4. hypalbuminaemia ( nephrotic sy, enteropathia with loss of proteins, malnutrition) 5. pancreatic
diseases, ovarial diseases ( Meigs syndrom ).
THERAPY:
* basic precautions: confinement to bed in hospital, abstinence of alcohol,diet with limited level of
natrium ( max. 3 g NaCl daily), reduction of fluids uptake to 1 litre per day, rather vegetarian foods.
* diuretics: basic precautions are usually deficient, in therapy are prefered aldosteron antagonists spirolacton 200-400mg/day, daily we meassure : weight, fluids uptake and output, abdominal
circumference, we monitor mineral levels in serum and urine (Na, K). If we don´t succeed it is
possible to elevate the spirolacton dosis to 800mg and to add furosemid or thiazid diuretic. Reduction
of ascites is necessary to perform slowly, diuresis should increase max. 1 litre daily. Decrease of
kalium in plasma to the levels round 3 mmol/l and encephalopathia are the reason to interrupt diuretic
therapy. Hyponatremia is due to dilution and bodily distribution, prolongated hyponatremia means bad
prognosis.
*paracentesis ( ascites puncture) in refractery ascites, in tensioned ascites and like the start step in
therapy of bulky ascites. During the puncture is necessary to perform prevention for saving of
plasmatic volume, the best is albumin infusion, temporary is albumin usually suplemented with Dextran
or Haemacel ( 6g / 1 litre of ascites = 100ml 6% solution)
* alternative methods are ascites reinfusion, or Le Veen shunt or TIPS (Transjugular Intrahepatic
Portosystem Shunt) implantation.
PROGNOSTIC AND REVIEW PROBLEMS: Prognosis is serious, patient has to be informed about
dietary, regimen and therapeutic precautions and their observance. Prognostic factors are determined
also with the basic disease which caused ascites. Based on these datas is given also review
problematic and individual access to patients.
LITERATURE:
Edema in Systemic Rheumatic Diseases.The wiew point of rheumatologist.
Doc.MUDr. Marie Valešová,CSc
Edema in rheumatic diseases
- usually the result of synovial membrane hyperplasia and inflammation (synovitis) which could be
followed by inflammation of the other structures of joint (arthritis).
- less frequently changes in skin, muscules, tendons, ligaments and their sheets and other so called
soft tissues.
The presence of swelling or excess of joint fluid is usually nonspecific often reflecting traumatic,
inflammatory or infectious etiologies. It can be due to increased levels of physical activity or the result
of a preexisting intraarticular lesion.
Etiology
is unknown
Pathogenesis
Ethiological agent is unknown - possibilities:
a) Infective agent
b) Alteration of immune system
c) Immunogenetical aspects
d) External factors which could led to disorders in nutrition, hormonal regulation, psychical stage etc.
or their combinations.
Immune mechanisms:
Acute or chronic inflammatory reaction of joint synovial membrane due to interaction among:
- lymphocytes
- macrofages
- polymorfonuclelear leucocytes-neutrofils
- other cells like fibrocytes, chondrocytes etc.
The interaction takes place inside the joint.
It is provoced by unknown factor, which comes into this milieu.
Immune response to this agent can be divided into four steps:
1.Accumulation of monoclonal cells and presentation of the antigen
2. Proliferation of lymphocytes
3. Local production of antibodies
4. Tissue injury by immune complexes
These immune processes led into nonspecific immune response and biochemical reactions. They
combine to releasing of degradational enzymes from macrophages, polymorphonuclears,
chondrocytes and from the cells of granular tissue, which forms inside the inflammed joint. The
substrate for enzymes activity are the macromoleculs of the connective tissue, cartilage and bone proteoglycans and collagen.
Pathology
Pathological changes in joints:
- vasculitis
- increased permeability
- multiplying of infiltrative T and B lymphocytes,
polymorphonuclears and plasmatic cells
The stroma of the joint surface is infiltrated by the cells which are multiplicated also inside the joint
cavity. The enzymes produced by the synovial and granulation tissue cells paticipate on joint
destruction, too.
Hydrops of the joint - patological increase of the joint fluid
swelling - change of joint shape
pain - from joint capsula distention and inflammation
They could be 3 types of fluid inside the joint
1) exudate 2) blood 3) pus
During the inflammation the character of the fluid could change
Typical clinical and laboratory findings
There is only a little of joint fluid in a normal joint. The capsula does not curve otwards. It is not
possible to demonstrate the fluid by palpation.
Only after patological excess of joint fluid production it is possible to distinguish fluctuation. By pressing
on one side of the joint increase of tension is felt on the other side of joint capsula.
In extraarticular structures like tendons an their sheets, ligaments, enthesis and muscles differentiation
of their edema is very difficult and needs some experience or it could be done only by imaging
methods.
Procedure of examination
Clinical
The joint has characteristic signs of inflammation
1) Increased temperature on the joint surface
2) Colour is usually unchanged ( erythema- redness could be seen only in arthrtitis of infectious origin
or crystal- induced arthritis)
3) Pain in the movement
4) Limitation of joint function
Laboratory
1)Analysis of synovial fluid
It provides the physician with unique and valuable information about what is going on inside joint.
2)Analysis of serum
Acute phase reactants, autoantibodies, circulating immune complexes, and immunochemical tests are
evaluated in the assesment of systemic rheumatic illnesses.
Imaging techniques and others
1) Conventional radiography, tomography
2) Computed tomography (CT)
3) Magnetic resonance imaging (MRI)
4) Arthroscopy
5) Biopsy (synovial membraine, bone, muscle, skin)
Treatment
Edema in systemic rheumatic diseases is a result of inflammation of the artricular or extraarticular
structures.
The aim of present therapy is to decrese joint inflammation, to provide pain relief, and more
importantly, to maintain or restore joint function and prevent bone and cartilage destruction.
1) Symptomatic medical therapy
- Nonsteroidal antiinflammatory drugs (NSAIDs)
- Corticosteroids
- Disease - modifying antirheumatic drugs (DMARDs) - antimalarial, sulfasalazine, parenteral gold
salts and cytotoxic agents.
2) Physiotherapy
3) Physical therapy - is a part of the treatment program. The goal of exercise is to maintain or improve
muscle tone, prevent or correct deformities and maitain or increase joint mobility and function.
Prognosis
Case reports
Literature:
Harrison´s Principles of Internal Medicine, Mc Graw Hill, 1995
Souhami,Moxham: Texbook of Medicine, Churchil Livingston ,1994
Kelley et al.: Textbook of Rheumatology, Saunders, Fourth Edition, 1994
Hormonal induced edema and edema due to disorders of nutrition
Oedemas due to starvation
Nutrition disorders:

definition

types: marasmus, kwashiorkor, combined disorders

adaptation and its metabolic consequences

main causes of malnutrition

main clinical consequences of malnutrition
Oedemas due to starvation:

pathogenesis

clinical picture
Oedemas of endocrine origin
Oedema is one part of some endocrine syndromas. Usually it is not dominant symptom. More often oedemas are
not visible but hyperhydration is present (increasing of body weight due to extracellular fluid expansion)
Oedemas due to hypothyreosis – myxoedema:

pathogenesis

clinical picture
Pathogenesis of water and electrolyte balance disorders due to:

Cushing´s disease and Cushing´s syndrome

Primary hyperaldosteronism –Conn´s syndrome

Pregnancy oedemas

Premenstrual oedemas
MUDr. J.Jenšovský
Hypothyroidism: classical appearance of patients suffering hypothyroidism is caused by periorbital
and peripheral oedema. Patients have rough features of the face, oedema of the upper lid, the skin is
coarse-grained and thick. There may be some problems in differential diagnosis between oedema of
the legs caused by cardiac failure and hypothyroidism. This classical description is quite rare
nowadays. Hypothyroidism is diagnosed in subclinical or only mild stages of the disease. Then the skin
is only dry and cold, there are no oedemas. The skin is mostly yellowish colour and pale. Patients with
hypothyroidism suffer anaemia quite often which contributes to this symptom.
The whole- body content of natrium and water is increased, plasma volume on the other hand may be
decreased. Patients may develop hyponatraemia, laboratory values of urea and creatinine remain in
normal range. Above mentioned characteristic features often result in visceral, pericardial and other
effusions. Typically cardiologists have keep in mind diagnosis of hypothyroidism in pericardial effusions
of unknown origin. Water retention may cause weight gain but-hypothyroidism is not the cause of
obesity.
Other hormones which may cause oedema are estrogens. These cause water retention during
menstrual cycle and are able to do the same in pharmacological doses/oral contraceptives, hormone
replacement therapy etc./. Excessive effusions can be seen in the "overstimulation" syndrome during
fertilisation attempts.
One of the new causes of hormonally dependent oedemas is treatment with growth hormone. Patients
with growth hormone deficit suffer from decreased water content and oedema during treatment is
marker of overtreatment. This should not happen in low-dose treatment and during gradually increased
doses of growth hormone.
References:
Wilson J.D. et al: Williams textbook of endocrinology, 9th ede., W.B.Saunders, 1998
Greenspan S.F et al: Basic and clinical endocrinology, 5th ed., Appleton and Lange, 1997
Edema and Starvation
1) Pathophysiology and biochemistry of starvation
2) Malnutrition – marasmus, kwashiorkor
a) clinical features of malnutrition - anamnesis, examination. Biochemical and metabolic
abnormalities in marasmus and kwashiorkor.
b) etiology of malnutrition
c) epidemiology of malnutrition
d) body composition in undernutrition
3) Case report
Literature
1) Diet, nutrition and the prevention of chronic diseases, Report of a WHO Study Group, WHO
Technical Report Series, No. 797, WHO, Geneva, 1990, p. 16-21
2) Brown M. L.(edit.): Present Kowledge in Nutrition, 6th Edition, ILSI Press, Washington, 1990, p. 39 46
3) Heepe F.: Diätetische Indikationen, Springer-Verlag, Berlin, 1990, p. 250-251
4) Hamilton E., Whitney E., Sizer F.: Nutrition: Concepts and Controversies, West Publishing
Company, St. Paul/New York, 1988, p. 159- 161, 537-567
5) Lener J. et al.: Medical Hygiene, Karolinum, Prague, 1997
6) Barasi M.: Human nutrition – a Health Perspective, Arnold, London, 1997
Edema in pregnancy
MUDr.R.Pokorný
Edema in a pregnancy is relatively frequent although its incidence is considered to be less
important in last few years. It is especially connected with preeclampsia and eclampsia
(edema, albuminuria, and hypertension) shortly with diseases connected with pregnancy. A
hypertension and an albuminuria in the pregnancy are called preeclampsia. This disease could
culminate in eclampsia itself, which is connected with high mortality of a pregnant (10%) and
a fetus (30%) as well.
It is generally presented that the edema is one of the first signs of the eclampsia. The first
stage of edema (perimaleolar) is from orthostatical reasons; the second one (peritibial)
requires higher attention especially if it remains after the night rest. The third one
(generalized), which is connected with edema of the face, requires particular examination of
the pregnant.
The edema in connection with hypertension and albuminuria makes the tries of the eclampsia
sings. But they also could completely fail in this disease.
Pathogenesis of this disease is not known yet. There are a lot of theories for instance
multifactorial or prostaglandin one, but no one explains ethiopathogenesis of this disease
completely.
Incidence of the eclampsia is more frequent in primiparae, especially very young women or
vice versa in women older than 30 years of age. Women coming from lower economic status
are also of higher risk of having this disease. Disposal factors for this disease are chronical
cardiovascular or renal diseases and diabetes mellitus as well. If there is the hypertension
before the pregnancy, we call that superimposed preeclampsia or eclampsia.
The most significant sign in clinical image of eclampsia is blood pressure with S/D 140/90
and more, proteinuria more than 0.3 g/l in 24 hours, generalized edema with increase of
weight more than 1 kg per week. The changes on a retina are although very significant the
headache including as well.
The symptoms are more frequent before the eclamptic attack. There is a kinetic anxiety,
disturbance of sight, emesis, nausea and epigastrium pain. The eclamptic attack itself starts
with tonic convulsions chewing and breathing muscles. The woman is in epistotonus and her
hands are closet in the fists. This status continues about 20-30 seconds. It passes in the clonic
convulsion with clones of facial and limbs muscles with rattling and spume in the mouth. It
takes about 1-3 minutes. This status passes in the eclamptic coma – the stage with deep
uncousniousness with a hyporeflexy and a dilation of the pupils but with deep and regular
breathing. Very common is total amnesia after this attack. The attacks could be repeated
(eclampsia status) or there could be unconsciousness without the convulsion status (eclampsy
without eclampsy).
Laboratory investigation: blood count, biochemical inv. of the kidney – uric acid is higher,
urea and creatinin are higher in harder status, biochemical inv. of the liver (SGOT, SGPT,
bilirubin is higher), iontogram, the value of protein could be lower.
There is a necessity of fetoplacental monitoring (HCG, estriol, ultrasound, ctg.).
Complications: Decrease of placental perfusion and chronical placental insufficiency could
cause in abruption of the placenta. In severe stages there could be the defect of coagulation of
blood, failure of renals, lungs edema and edema of the brain.
Differential diagnosis could be epilepsy, hypoglycemia, uremic coma, and tumors of the brain,
hysteria.
Therapy: The most important is the prevention and timely diagnosis of the first signs of the
disease during the prenatal care. In the lighter cases is recommended diet sedative therapy
(plegomazine diazepamum), hypotensives (dihydralazin) quiet atmosphe recontinual care
about the pregnant, fetoplacental unit, MGS04.
In severe stages the sedatives hypotensives MGSO4 and diuretics are recommended,
hypertonic solutions, albumin quiet and dark place. If the conservative therapy fails, there is
necessary to terminate the pregnancy apart from the fetus. Cesarean section is mostly
recommended.
Recommended literature:
Macků – Porodnictví
V. Fuchs – Nemoci v těhotenství
G. Martius, M. Beckworld, A. Pfleiderer – Gynekologie a porodnictví
Z. Štembera, K. Poláček, V. Vlach – Rizikové těhotenství a dítě
B. Vedra – Hypertensní a renální choroby v těhotenství
Edema of upper
airwais
Brain edema
Doc.MUDr. Pavel Kalvach,CSc.
A)
Neurological Aspects of Brain Edema
a)
Brain edema means an increased hydratation of cerebral tissue. The elevated volume of water
is situated either inside of the cells - as in intracellular edema, or in the intersticium - as in extracellular
edema. The etiology of both these types of brain edema is different.
Intracellular edema arises from cytotoxic or ischemic or traumatic causes. In a failure of the
Natrium - Kalium pump on the cellular membrane Natrium enters into the cells and Kalium escapes out
of the cells. Na - due to its higher solvatation pulls water inside, the cell swells and the tissue augments
its volume. The expanding effect of the damaged tissue is prone to compress the surrounding tissue
and to spoil its perfusion gradients. This type of edema is immobile, bound locally to the cellular
cytoplasm. On a cut through the tissue the water doesn´t flow out and consequently this edema has
been earlier designated as a "dry" edema.
Extracellular edema appears from vasogenic reasons. This means an abnormally loosened
blood-brain-barrier (BBB). The plasmatic filtration crosses the BBB, in contradistinction to the
intracellular edema, where a plasmatic ultrafiltration is being moved into the cells. The extracellular,
intersticial edema is mobile and does not cause an expansion of the lesion. Due to its mobility it
spreads according to the hydraulic laws in a direction of the least resistance. Therefore it dwells
preferentially in the white brain matter. On a tissue cut it flows out and so it deserved a designation
"wet" edema. Its specific form is the periventricular intersticial edema, arising in the tight
neighbourhood of cerebral ventriculs in obstructive hydrocephalus.
b) The augmented brain volume due to edema is a dangerous state in the closed intracranial (i.c.)
space. In smaller lesions the compression of capillary perfusion affects the immediate surroundings, in
bigger lesions it puts in danger even distant parts of the brain. The increasing brain hemisphere
pushes the midline to the other side and exerts pressure on contralateral structures against narrows of
the i.c. space. This is important mainly in the tentorial incissure and in the great occipital foramen. The
clinical signs therefore are due to local damage as well as to general i.c. hypertension. The focal
signs are combined in more severe stages with conus signs.
c) The particular local lesion in intracellular edema is caused by the original etiology (most often
ischemic malacia in perfusion failure) in the extracellular edema by the damaged blood-brain-barrier (in
tumors, abscesses, metastases or in later stages of ischemic infarction).
d) The local edema should be understood as a consequence of the primary pathology in the
centre. It is substantial to distinguish the initial stages of intacranial hypertension and conus signs:
headache with vomiting, meningeal syndrom, a developing peduncular mesencephalic lesion and signs
of a compressed oblongata with a severe brain stem syndrom. The asymetry of pupills with signs of a
rostro-caudal deterioration of the brain stem are leading symptoms in our examination.
e) The therapy of a cytotoxic/ischemic edema is based on the treatment of the primary etiology.
Most often then on attempts to improve brain circulation (anticoagulation, thrombolysis, improvement
of blood viscosity, securing of cardiovascular efectivity). The extracellular edema is usually treated by
corticosteroids. In urgent conus stages the most important step is a restauration of CSF (cerebral
spinal fluid) pathways in cases of obstructed CSF straits: a surgical shunting - usually from the lateral
ventricle.
f) The preservation of vital functions in intensive care units (ICU) can save life in many patients
with edema. The critical period may often be only 7 till 10 days. The healing of the original - particularly
traumatic or cerebrovascular affection - often brings, after surpassing of the acute stage, a dramatic
improvement.
B)
Neurogenic edema in somatic tissues
A tissue edema in afflictions of peripheral nerves is rare. Sometimes chronic edema
complicates a reflex sympathetic dystrophy, usually in its severe stages. The pathogenetic mechanism
of its rise in this disease is unknown.
Another rare phenomenon is a neurogenic lung edema. The pathogenetic principle is a sudden
elevation of intracranial pressure, for instance in i.c. bleeding. This elicites an increase of systemic
pressure. The accute elevation of peripheral resistance, trying to compensate cerebral perfusion, may
lead to a left-sided heart faillure with a consequent lung edema.
Literature:
Raymond D.Adams, Maurice Victor: Principles of nerology, New York, St. Louis, San Francisko, McGrawHill,1977, 1286 pgs.
Anne G Osborn: Diagnostic Neroradiology, St. Louis, Baltimore, Boston, Mosby, 1994
Edema in burns
MUDr. Monika Valová
A) Pathogenesis : 1. Disorder of volume homeostasis ( disorder in Starling ´s
homeostasis ) :
a)
vasodilatation precapillary
b)
increase of interstitial osmotic pressure
c)
obstruction of veins distal
d)
increase of microvascular permeability for macromolecules ( collapse of
microcirculation )
e)
damage of endothelium by thermal noxa
f)
decrease of oncotic plasma pressure , loosening of the interstitial matrix,
hypoproteinemia
g)
disorder of cell membrane by decrease of general membrane potential
a)
b)
c)
d)
e)
f)
2. The hormonal and humoral aspects :
activation of the sympathoadrenal and hypothalamic-pituitary-adrenal
axis, shock mediators
the renin – angiotensin –aldosterone system
ADH
kallikrein – kinin system
clotting and fibrinolytic cascade
complement system
arachidonic acid cascade
B) Sorts of the edemas : 1. Local :
a)
collateral edema in burns, specific form of edema in electrical burns
b)
visceral forms of local edemas – cardial and non-cardial edema of lungs,
edema of brain, hydrops ( hydrothorax, hydropericardium, ascites )
c)
the other forms of edemas – for example blockade of venous outlet,
lymphedema,
inflammatory edema, allergic, static edema , edema like complication of internal
diseases, iatrogenic edemas
2. General :
a)
interstitial and intracellular edema
b)
general forms of edemas in visceral involvement ( cardial, renal, hepatic )
c)
iatrogenic general edemas of extracellular space – overexpansion
C) Diagnostics :
1. Physical investigation
2. Laboratory investigation
3.
Monitoring of the basic vital
functions ( total, visceral
circulation, plasma volume )
4.
visualizing methods ( US,
Doppler, echocg ,rtg, CT, DSA,
phlebographia, lymphographia)
D) Therapy :
goal : restore and maintain perfusion of tissues, first in the level of
microcirculation , prevent from the tissue ischemia , prevent from
the development of multiple organ dysfunction and failure
1.
Principles of replacement fluid therapy in burns
2.
Monitoring of total, visceral circulation, plasma volume
3.
Therapy of hypovolemic shock :
a)
sorts of resuscitation solutions
b)
sorts of resuscitation diagrams according to extent, weight, age, body surface
c)
complication of therapy ( local, total, visceral )
C) Prognosis : according to weightiness of burns :
1.
mechanism of thermic injury
2.
extent and depth
3.
age of patient
4.
localization
5.
anamnesis – personal, family, work
D) Verdict standards :
1.
forms of injuries ( work, out – of work )
2.
mechanism of injury
3.
extent, depth, localization of injury
4.
age of patient
5.
permanent consequences
6.
anamnesis
7.
criminal acts
E) Case Studies
Literature : Rozsáhlé popáleninové trauma, Avicenum , the second printing ,1990, Prof. MUDr.
Radana Konigová, spol.
Total Burn Care, D. N. Herndon, W. B. Saunders Comp., 1996, the second printing
Burns management , John A. D. Settle, Churchill Livingstone, 1996, the first
printing
Edema – allergy or idiosyncrasy
MUDr. P.Kučera
Pathogenesis
Angioedema (angioneurotic edema, edema Quincke) is caused by edema of deep dermis and
subcutaneous tissue. An area involved with angioedema has swelling as the prominent manifestation,
the appearance of skin can be normal or can occur together with urticaria, erythema. It lasts about 24
to 72 hours.
The pathogenesis and trigger factors of allergic edema are very heterogeneous. The basic
mechanism is the basophil and tissue mastocyte activation and releasing of vasoactive mediators.
Histamine, tryptase and chymase are the most important one, causing the early symptoms of edema.
Later released mediators, like cytokines, arachidonic acid metabolites amplify allergic reaction.
Mastocyte activation is caused by bridging of two high affinity receptors for IgE (FcRI) or by
nonimmunologic pathway, stimulation by morphine, codeine, substance P. Sometimes, the exact
mechanism is unknown.
Decreased concentration or low function of C 1 inactivator is a pathway of hereditary
angioedema ( HAE). This swelling is based on increased vascular permeability caused by kinin-like
mediators, activated proteins from complement cascade.
Symptoms and laboratory findings.
Angioedematous swelling often involves the face (eyelids or cheeks), tongue, extremities or
genitalia. They are asymmetrically distributed and transient, angioedema and urticaria can occur
together. In deeper skin layers are fewer mast cells and sensory nerve endings, the lesions have little
pruritus and swelling may be painful or burning. Hereditary angioedema is not associated with urticaria,
skin lesions, visceral involvement (laryngeal edema, gastrointestinal wall edema) are typical.
Abdominal attacks last usually 3-4 days, they can be inherited or acquired.
Diagnosis, differential diagnosis
Diagnosis is based on clinical symptoms.
Investigations
Etiopathogenetic diagnosis is based on the data from past history, the past history can bring
information about impact of allergens or nonimmunological triggers. We can test the type I
hypersensitivity by allergen skin tests, measuring of specific IgE in serum. Typical finding for hereditary
angioedema is quantitative of functional drop of C I inactivator, C2 or C4 parts of complement.
Treatment, aspects depending on locality and etiology
Therapy of acute attacks consists of antihistamines, adrenaline, corticosteroids. In the case of HAE
we use steroids, sometimes adrenaline, preferentially C I inactivator concentrate, preventive treatment
consists of anabolic steroids. Treatment has to be aggressive in the cases of edema with high risk –
airway or gastrointestinal obstruction.
Approach to the patients
There is usually no problem to setup the diagnosis, but part of patient with angioedema doesn’t
respond to therapy, patients are usually able to work.
Cases will be demonstrated during tutorials
References:
Stites DP, Terr AI,: Základní a klinická imunologie, Victoria Publishing a.s. Praha, 1994
Fucíková T: Klinická imunologie v praxi, Galén 1993, 1995
Kay AB: Allergy and Allergic Diseases, Blackwell 1997
Literature :
B.G. Katzung : Basic and Clinical Pharmacology
7th edition, Prentice-Hall International , 1998
Rang, Dale, Ritter : Pharmacology
3rd edition, Churchill Livingstone, Edinburgh, 1995
Mycek, Harvey, Champ : Lippincott´s Illustrated rewiews Pharmacology
2nd edition, Lippincott-Raven, Philadelphia, 1997