The theme of the lesson

HEMORRHAGIC FEVER WITH RENAL SYNDROME (HFRS)

The causative agents: viruses of Bunyaviridae family. In Russia more

often Hantaan virus is isolated (it circulates in natural focuses of the Far East
and also in Korea, China, Japan) and Puumala (European, western variant; it
circulates also in Scandinavian countries, in Europe).

The source of the infection. The main reservoirs and sources of Hantaan
virus – are field mice, red-gray field-voles and Asiatic forest mice, of Puumala
virus – red field-voles (in endemic focuses of Central Russia their contamination
amounts to 40-57%). In cities house mice can be reservoirs of the infection. The
rodents excrete the viruses together with feces and urine. Contamination of a
man happens in an air-dust way, more seldom – during contacts with rodents
and infected objects of environment (brushwood, hay and others), in an
alimentary way – through vegetables, which are not heated. People are not
sources of the infection for those around them.

Pathogenesis. The basis of the pathogenesis – is an injury of vascular

walls, including renal vessels, a damage of endothelium of renal tubules. If the
clinical course is sever, glomerular filtration decreases significantly,
thrombohemorrhagic syndrome appears. Apparent autoimmune reactions
promote acute renal failure.

Clinical presentation
The incubation period is from 7 to 46 days, on average 2 weeks. The first
period – is febrile – it breaks out acutely, with chill and rise of temperature to 38
– 40оС and above. Fever can last for 7–8 days, in severer cases it also continues
during the next period. The patient complains of headache, weakness. There is
hyperemia of face, the upper part of chest, injection of sclerae and conjunctivas,
hyperemia of the fauces (without catarrhal occurances). A short-term visual
impairment is typical (insufficiency of accommodation: for example,
impossibility to distinguish a clock dial, small text). During this phase of the
disease there can be nausea, vomiting, heaviness and tenderness in the lumbar
region.
On the 2-4th day of the disease oligoanuric period starts. Symptoms of
intoxication augment; hemorrhagic syndrome appears (petechial hemorrhages
on skin, sclerous, nasal, gastric and intestinal hemorrhages). Renal insufficiency
progresses. Temperature, as a rule, falls. Objectively the patients have edemas:
puffy faces, pale eyelids. Visual acuity decreases. There is relative bradycardia,
hepatomegaly, a sharp tenderness during palpation in the lumbar region.
Palpation of the loins (Pasternatsky's symptom) is painful on the both sides –
 2

symmetrically. Test of this symptom requires a special caution, since kidney

rupture can happen. The duration of the period is 5 – 8 days (up to 8-11 days of
the disease).
The period of an early recovery (on the 9 – 12th day of the disease)
declares itself by polyuria, intoxication abatement, there is a gradual
amelioration. Daily urinary output amounts to 3-5 liters; there is still weakness,
dry mouth. Gradually – from the 20-25th day – recovery period begins.
Lethality, on average, is 0.2 – 0.5% (in Russia – up to 2%, taking into
account data of the Far East, where the disease proceeds severer, owing to
peculiarities of Hantaan virus).
Complications are: infectious-toxic shock, acute renal failure,
hemorrhages in vitally important organs (brain, adrenal glands), kidney rupture,
pulmonary edema, pneumonia, meningoencephalitis. During polyuric period
cardiac rate disturbances, enteroparesis occur due to a loss of electrolytes.
The severest complication of HFRS – is acute renal failure (ARF). It
progresses at the peak of oligoanuria; it is characterized by augmentation of
intoxication, azotemia and hyperpotassemia. Headache, anxiety, thirst,
xeroderma, vomiting, meteorism, gastrointestinal hemorrhages, disorders of
consciousness (encephalopathy) are observed. Nitrogen-containing substances
accumulate; levels of rest nitrogen, creatinine and urea in blood increase. In the
stage of polyuria an excretion function of kidneys is still impaired, dehydration
and hypokaliemia are possible.

Laboratory diagnostics. Specific diagnostics – detection of antibodies in

FIA or other serological reactions. For reliable diagnostics it is necessary to
carry out the investigation at an interval of 7 – 10 days, at least of two blood
serums of the patient. An increase of antibody titer in 4 and more times is
diagnostic.
Nonspecific diagnostics (clinical methods)
It is recommended to carry out urine examination (relative density,
proteinuria, hematuria, cylindruria) every day. Proteinuria is a permanent
symptom of HFRS from the 4 – 5th day of the disease (from 1-2 to 30 g/l and
more). Concurrently micro- and macrohematuria, cylindruria are registered in
the cases. Urinary output during the first period can be normal or decreased,
during the period of oliguria there is its decrease, and during the final period
there is hyposthenuria and isosthenuria, which are detected with the help of
Zimnitskiy's test.
During the peak of the disease hypoproteinemia, disproteinemia and
azotemia are detected. Level of potassium in blood serum during oliguric period
increases, during polyuric one – it decreases to hypokaliemia.

Treatment. Usually etiotropic preparations are not used; there are data on
an effectiveness of amikacin. Pathogenetic treatment includes disintoxication
 3

therapy, normalization of microcirculation, fight against acute renal failure and

correction of water-electrolytic imbalances.
Volume of introduced solutions during oliguric period must correspond
with the volume of excreted liquid (measurement of diuresis is obligatory!). It is
recommended to introduce concentrated solutions of glucose (20-30% solution –
500.0 ml with insulin), 4-5% solution of sodium bicarbonate (100-200.0 ml),
10% solution of calcium gluconate (40.0 ml) intravenously. It is possible to
stimulate urine passage once: 200.0 ml of 5% solution of sodium bicarbonate,
then 10.0 ml of 2.4% solution of aminophylline, then 10.0 ml of 1% solution of
furosemide. It is not recommended to use mannitol, urea, mercurial diuretics
with the purpose of stimulation of diuresis; it is not advisable to introduce
glucocorticosteroids (they increase azotemia and hyperpotassemia).
During polyuric period water-electrolytic losses are restored naturally (by
drinking).
Antibacterial drugs are used in case of bacterial complications;
prescription of nephrotoxic antibiotics is very undesirable.

Hospitalization is obligatory (by clinical indications).

Isolation of the patients and contact with them people (communicating
with the patients) is not allowed.
Conditions of being discharged from hospital are: clinical recovery,
normalization of all laboratory indices. Isohyposthenuria can remain.
Prophylactic medical examination: It is carried out during not less than
six months. During the first three months after the disease laborious physical
activity is not allowed.
Specific prophylaxis: It is not carried out in Russia.

CONDUCTION OF THE LESSON

The aim – is to learn how to diagnose HFRS according to clinical data,

epidemiological anamnesis, laboratory examination, as well as to plan its
treatment.

Control questions at the beginning of the lesson:

1. Where is HFRS common?
2. Name the source of the infection in case of HFRS
3. Is a man a source of the infection in case of HFRS?
4. Channels of HFRS
5. What happens in kidneys during HFRS?
6. Name clinical periods of HFRS and their approximate durations
7. Which symptoms indicate a severe course of HFRS?
 4

8. Which changes in urine are typical of oligoanuric period of HFRS?

Polyuric period?
9. Name laboratory methods for confirmation of HFRS diagnosis.
10. Name groups of preparations for treatment of HFRS

To discuss the theme of the lesson a student manages a patient, makes a

brief report about the patient’s history (in the absence of the patient with HFRS
in the department). It is necessary to find out the following data about the
patient:
Surname, name, patronymic name; age, place of work and residence (city,
village), date of the falling ill;
Complaints at the present time.
The first symptoms of the disease: temperature rise (to which level, for
how many days), intoxication, appearance of pains in the low back (when,
symmetrically, was there irradiation of the pains in the abdomen because of a
significant enlargement of the kidneys). It is necessary to pay attention to visual
acuity, a possible appearance of eruption.
When did the patient notice a decrease in urinary output? How many days
did it last (or has it lasted by the day of the management)? Which derangements
of health troubled the patient?

When and how (presumably) did the contamination of the patient happen?
It is necessary to find out epidemiological anamnesis: sanitary living and
feeding conditions, presence of rodents at home, trips to the countryside. What
is the duration of the incubation period?
Objective data of the patient’s examination: condition, color of skin,
presence of dryness or edema of skin and mucous membranes, appearance of
skin rash. Condition of the cardiovascular (tachycardia, arrhythmia; pulse rate,
level of arterial pressure when it was measured by a doctor last time) and
respiratory system, gastrointestinal tract (presence of erosions, hemorrhages,
enteroparesis – during examination, palpation and according to indirect signs). A
special attention should be paid to condition of urinary system: diuresis, color of
urine, tenderness during palpation of the lumbar region – test of this symptom
must be carried out very carefully!

Case history of the patient with HFRS is discussed in the group. The
students together plan the examination of the patients. The teacher introduces
the students to the results of the laboratory examinations. On the basis of all
available data the students make out a diagnosis indicating a period and severity
of the disease. The treatment is discussed. The students together plan the
treatment of the patient, discus it with the teacher. Making out this plan it is
necessary to take into consideration a period of the disease, urinary output
 5

during a day – depending on it, to determine the volume of the introduced fluid.
It is necessary to discuss a list of preparations, normalizing microcirculation in
kidneys, as well as indications for prescription of diuretics and usage of
extracorporal hemodialysis.

At the end of the lesson the students do clinical tasks and answer the
questions to them. Accomplishing the tasks the students write in their copy-
books:
clinical diagnosis (taking into consideration the form and severity of the
disease);
plan of the patient’s examination;
they write out in Latin preparations having antibacterial and pathogenetic
actions.

Task №1
A male patient P., aged 30, consulted a therapeutist on 15 October,
complaining about weakness, headache, chill, raise of temperature to 380С,
photophobia, visual impairment (diffusiveness of objects), low back pains.
Case history. The patient fell ill on 8 October, when he felt an intense
headache, weakness, pains in joints. Temperature rose to 37.50С. During the
ensuing days the patient felt worse, low back pains appeared; he didn’t consult a
doctor. On 14 October temperature rose to до 390С, weakness augmented, low
back pains intensified. Eyesight became worse: illegibility of contours of some
objects occurred; he couldn’t read text, written in a small print. On skin rash
appeared. There was nosebleed twice a day.
Objective examination: general condition is mild. Skin is hyperemic. On
the shoulders and back – there is a petechial skin rash. In the lungs the
respiration is vesicular. Heart sounds are muted, the rhythm is regular. The pulse
is 66 beats per minute. АBP – is 100/60 mm of mercury column. Pasternatsky's
symptom (palpation) is positive on the both sides. Stool is normal.
Epidemiological anamnesis: from 11 September till 9 October he was in
the countryside. In a house, where he lived, there were a lot of mice.

Questions:
1. What is a presumptive diagnosis?
2. Plan of the examination
3. With which disease it should be differentiated?
4. Therapeutic approach (conditions of transportation and hospitalization;
treatment).

Task №2
 6

A male patient А., aged 25, was admitted to infectious diseases

department on 5 August, complaining about weakness, headache, rise of
temperature to 38.70С, pains in the loin and in both hypochondrial regions.
Case history. The patient fell ill on 1 August, when chill, headache
appeared, temperature rose (de didn’t measure it, but felt fever). From the 3d day
of the disease – temperature was 39 – 39.50С, there were pains in the loin and
hypochondrial areas, vomiting happened 1-2 times a day.
Objective examination: state is mild. Skin is of a normal color. In the
lungs the respiration is vesicular. Heart sounds are muted, the rhythm is regular.
The pulse is 66 beats per minute. АBP – is 100/60 mm of mercury column.
Pasternatsky's symptom (palpation) is positive on the both sides. Stool is
normal.
Epidemiological anamnesis: during the last month the patient was in the
countryside, he was busy with farm work: picking of hay in the barn.

Under medical observation in the hospital a decrease in diuresis was

detected to 400-500.0 ml per day during 6-8 August;
In the common urine analysis: relative density – was 1006, protein – 3.3
g/l, leukocytes – to 10 in visual field, erythrocytes – 20-25 in visual field, there
was a significant quantity of hyaline and granular cylinders.
On 9 August the patient got 1200 ml of liquid (drank and intravenously),
he excreted 1100 ml together with urine. From 10 August – there was an
increase in diuresis to 2500 ml, then – to 3500 ml per day. Relative density of
the urine – was 1003.
On 13 August – there was cardiac rhythm disturbance in the form of
extrasystole.

Questions:
1. What is a presumptive diagnosis?
2. Plan of the examination.
3. Plan of the treatment.