Special Pathology. Diffuse Toxic Goitre

Diffuse Toxic Goitre

Diffuse toxic goitre (thyrotoxicosis, Basedow's disease) is caused by thyroid hyperfunction. The disease most commonly occurs in women be­tween the ages of 30 and 50; the incidence in men is 5-10 times lower.

Aetiology and pathogenesis. Psychic trauma, infection (tonsillitis, rheumatism, etc.), dysfunction of other endocrine glands (pituitary) are important for the development of the disease. Familial factors are also im­portant: toxic goitre can often be found in close relatives.

Secretion of hormones by the thyroid gland is intensified in stimulation of hypothalamic centres which stimulate secretion of the thyrotropic hor­mone by the anterior pituitary lobe. The hypothalamic centres can be stimulated by various factors, by psychic traumas in the first instance. In­vestigations of V. Baranov and other authors demonstrate the essential role of the central nervous system in the pathogenesis of diffuse toxic goitre. The authors have proved that in many patients the development of toxic goitre was preceded by neurocirculatory dystonia which interferes with ¹³¹I capture by the thyroid gland. This form of neurosis is now given great significance in the pathogenesis of diffuse toxic goitre and is regarded as a precursor of this disease.

Hyperthyroidism causes changes in various tissues and organs and disturbs various types of metabolism: protein-carbohydrate, fat, mineral, water metabolism, etc. Upset function of the sympathico-adrenal system is

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■ 385

also a very important factor which accounts for many symptoms of the disease. The role of the pituitary gland in the pathogenesis of thyrotox-icosis cannot be ruled out completely because patients with thyrotoxic goitre suffer from exophthalmos, while the exophthalmic factor is secreted by the pituitary gland.

Pathological anatomy. The thyroid gland enlarges uniformly or by focal hyperplasia; hence diffuse or nodular goitre. Microscopy shows intense blood filling in the thyroid gland and reconstruction of follicular epithelium into columnar or polymorphous epithelium. Sometimes the affected thyroid gland differs only insignificantly from the normal one by the character of its epithelium and follicles; the follicles may only have cyst-like dilatations and contain little colloidal substance. Lymphocytes are accumulated and lymphoid follicles are formed.

Clinical picture. The onset of the disease may be acute or gradual, with slow development of the symptoms. The main signs of the disease are enlargement of the thyroid gland, ocular signs, and heart palpitation. The patients complain of increased psychic excitability, non-motivated anxiety, deranged sleep, hyperhidrosis, tremor of the fingers or in the entire body, frequent defaecation, wasting, and muscular weakness.

Inspection of the patient immediately reveals the special features in his behaviour: fussiness, hasty speech; sometimes the patient drops the subject quite unexpectedly and starts discussing another subject. Ophthalmopathy and some other ocular symptoms suggest hyperthyroidism. Despite preserved or even increased appetite, the patient may lose much of his weight (to cachexia). The patient's skin is smooth, warm and moist to the touch. Some patients develop diffuse pigmentation of the skin which however does not colour the mucosa. The pigment is sometimes deposited selectively in the skin of the eyelids. The hair of the head becomes thin and soft.

During inspection special attention should be paid to the size of the thyroid gland and symmetry of its enlargement. If the thyroid gland is enlarged significantly, the patient's breathing becomes stridorous. Inspec­tion of the patient should be followed by palpation of the thyroid gland. Five degrees of thyroid enlargement are distinguished: I—enlarged thyroid gland is difficult to palpate; II—enlarged thyroid gland is clearly seen dur­ing swallowing; III—clearly visible thickening of the neck due to goitre; IV—marked goitre; V—large goitre. Enlargement of the second and third degree occurs most frequently.

Ocular symptoms. A common symptom of diffuse toxic goitre is bilateral dilation of the eye slits which gives an expression of astonishment to the patient's face. Another frequent manifestation is Graefe's sign: a white strip of sclera between the edge of the eyelid and the upper margin of

" Us

Fig. 112. Positive Graefe's symptom in thyrotoxico-sis.

the cornea which appears as the eyeball moves downward (Fig. 112). Among other symptoms are Stellwag's sign (infrequent blinking), Kocher's sign (exposure of the sclera between the lower edge of the upper eyelid and the upper edge of the iris when the eyes are fixed on an upwardly moving object), and the exophthalmic symptom (protruded eyeballs). The protru­sion is usually more or less uniform but asymmetry is also possible. One eye can only be involved in some cases. In grave exophthalmic goitre, keratitis, ulcers of the cornea can also develop and the patient's power of vision can thus be endangered. The eyelids can swell, and weakness of con­vergence can be observed; the eyeball can move aside when attention is fixed on a slowly approaching object (Moebius' sign). This symptom is associated with upset function of the oculomotor muscles.

Cardiovascular system. Tachycardia is one of the most frequent symp­toms of the disease. Pulse rate varies within the range of 90 to 120 and in grave cases to 150 beats per minute. Systolic and minute volumes, the mass of the circulating blood and the rate of the blood flow increase, systolic pressure grows, diastolic pressure falls, and the pulse pressure increases. Auscultation of the heart reveals a snapping first sound and systolic mur­mur at the apex and over the pulmonary artery which are due to increased blood flow rate and low tone of the papillary muscles. A most frequent and serious complication is atrial fibrillation (tachysystolic form) due to the toxic effect of the thyroid hormones on the myocardium. Circulatory in­sufficiency can also develop. Electrocardiograhic studies reveal a slightly increased amplitude of all waves (especially of the T wave), sinus tachycar­dia, extrasystole, and atrial fibrillation. X-rays examination reveals a slightly enlarged left ventricle of the heart.

Gastro-intestinal tract. The appetite increases. The increased motor

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function of the intestine accounts for diarrhoea. Hepatic dysfunction can have various effects: from slight disorders (that can only be revealed by functional tests) to cirrhosis.

Nervous system. The clinical symptoms of disorders in the higher ner­vous activity are excitability, increased reactivity, general motor restlessness, fidgetiness, and fine tremor of the fingers of the stretched arms (Marie's syndrome).

Endocrine system. A pronounced clinical picture of the disease is at­tended by a marked hypofunction of the sex glands (amenorrhoea) and of the adrenal cortex (hypoadrenocorticism); diabetes mellitus can join the process.

Study of the peripheral blood can reveal hypochromic anaemia, leukopenia, and lymphocytosis. Biochemical studies of blood reveal the tendency to hypocholesterolaemia and hyperglycaemia.

Basal metabolism increases by 50 and sometimes by 100 per cent. Tests with ¹³I show accelerated and increased absorption of radioactive iodine by the thyroid gland, an increased content of protein-bound iodine, and decreased excretion of iodine in the urine. The body temperature is usually subfebrile.

Course. The course of the disease depends on the gravity of thyrotox-icosis and is divided into three degrees: I degree thyrotoxicosis is characterized by the absense of complications; wasting is not marked, tachycardia is moderate (to 100 beats per min), basal metabolism increases not more than by 30 per cent; the symptoms are pronounced in II degree of thyrotoxicosis (wasting is considerable, symptoms of nervous disorders are marked, tachycardia from 100 to 120 beats per min, basal metabolism in­creases by 30-60 per cent); III degree thyrotoxicosis: grave forms of the disease with pronounced symptoms (rapidly developing cachexia, marked psychic excitability and other nervous symptoms, pronounced tachycardia, over 120 beats per min, basal metabolism increased by more than 60 per cent). Forms of the disease complicated by atrial fibrillation, heart failure, affections of the liver, and psychoses are also referred to III degree thyrotoxicosis.

The main complications in thyrotoxicosis are affections of the internal organs, e.g. the heart or the liver, and also psychoses, hypoadrenocor­ticism, and thyrotoxic crisis.

Treatment. The patient should be given calm and rest; sleep should be normalized. The diet must be adequate, rich in proteins and vitamins. An-tithyroid preparations should be given: iodine, thiouracyl, and imidazole derivatives. Transition from the second to the third degree is a positive in­dication for surgical intervention, irrespective of the length or gravity of the disease.

Chapter 10. Endocrine System and Metabolism 587

i Hypothyroidism

Hypothyroidism is the pathological condition associated with thyroid hypofunction. Hypothyroidism can be primary and secondary. Primary hypothyroidism is the primary pathology that arises in the thyroid gland, while secondary hypothyroidism depends on dysfunction of other organs that can affect the thyroid gland function. Grave forms of hypothyroidism are usually called myxoedema.

Aetiology and pathogenesis. Factors causing the onset of primary hypothyroidism are hyftoplasia or aplasia of the thyroid gland, iodine defi­ciency in the body, subtotal thyroidectomy, overdosage of ¹³¹I (which is given in hyperthyroidism) or preparations of thiouracil group, acute (in the past) or chronic thyroiditis. Hyposecretion of thyroxine and tri-iodthyrosine upsets normal metabolism and causes changes in tissues, organs, and systems of the body.

Pathological anatomy. Morphological changes in the thyroid gland are marked hypoplasia, aplasia, or atrophy. Hyperplastic changes occur in the thyroid gland in hypothyroidism caused by disordered synthesis of the hormones associated with the defective enzyme systems.

Clinical picture. The main complaints are apathy, lack of interest in the surroundings, impaired memory, decreased work capacity, somnolence, flaccidity, and chills.

The patient's appearance is quite specific: the eye slits are narrow, the face is puffy, the neck oedematous, the skin is pallid with a yellowish hue, sometimes with blush on the cheek bones. The skin is rough to the touch, thick, dry, cold, and scaling. The skin is thickened due to accumulation in it of mucopolysaccharides which give the impression of oedema. As distinct from oedema, pressure on the skin does not leave depressions. Hair on the head is rare; it falls off from the brows. Movements are slow and speech is monotonous.

Central and peripheral nervous systems. The mentioned complaints are associated with changes in the function of the central nervous system. Psychosis may develop in long-standing hypothyroidism. Disorders in the peripheral nervous system are manifested by strong severe radicular pain in the extremities, paraesthesia, cramps, and shaky gait.

Cardiovascular system. Bradycardia develops; the minute blood volume decreases and the blood flow rate is slow. The heart sounds are dulled. Fluid containing much protein and mucinous substances if often accumulated in the pericardium; it can be accumulated also in the pleural and abdominal cavity. Systolic pressure falls while diastolic pressure re­mains normal. ECG shows low voltage, especially inP and T waves. Heart failure develops in rare cases.

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Gastro-intestinal tract. Hypo- and achlorhydria often develops. The in­testinal motor function is decreased, constipation and meteorism develop.

Metabolism. Protein synthesis is decreased. Blood cholesterol is usually increased. Moderate hypoglycaemia is observed. Electrolyte level remains unchanged in most cases. Blood calcium sometimes decreases, and ESR in­creases.

Reduction of basal metabolism to 50 per cent and also of the protein-bound iodine is of great diagnostic significance. Absorption of ¹³¹I in the thyroid gland is low.

Myxoedema coma may develop in grave cases.

Treatment. Thyroid preparations are mainly used to treat hypothyroidism and coma.

Diabetes Mellitus

Diabetes mellitus is characterized by metabolic disorders associated with absolute or relative deficiency of insulin production. Diabetes mellitus is a frequently occurring disease. People between the ages of 40 and 60 are mostly affected.

Aetiology and pathogenesis. Organic or functional affection of beta cells of the pancreas islets is the main factor in the pathogenesis of diabetes mellitus. This affection accounts for insufficient synthesis of insulin. Primary insufficiency of these cells can arise after infection, psychic trauma, removal of the pancreas, its destruction by a tumour, sclerosis of the pancreatic vessels, in pancreatitis, regular overeating, or insufficient in­take of substances required for the normal function of the insular ap­paratus. Familial predisposition (genetically determined functional insuffi­ciency of beta cells) is a background against which the diabetogenic effect of the named factors is realized.

Secondary insufficiency of beta cells can be due to endocrine dysfunc­tion: pituitary, adrenal and thyroid hyperfunction. Somatotropic and thyrotropic hormones, corticotropin, glucocorticoids and glucagon have diabetogenic properties and are called contrainsulin hormones. The pathogenesis of diabetes mellitus also depends on the presence of excess in­sulin inhibitor, i.e. enzyme insulinase (which is produced in the liver and is activated in the anterior pituitary hyperfunction) and also insulin an­tagonists and antibodies to insulin contained in the blood of patients.

Hyperglycaemia is a symptom of disordered carbohydrate metabolism. Increased blood sugar content is associated with a slowed glucose supply to the muscles and fatty tissue and its slow phosphorylation. This interferes with glucose decomposition, synthesis of glycogen, and conversion of car­bohydrates into fats. High blood sugar depends also on intensified glucose

supply from the liver to the blood and formation of glucose from glycogenic amino acids. Hyperglycaemia is usually attended by glycosuria, which in turn depends on an increased amount of glucose in the glomerular filtrate and its complete reabsorption in the tubules. Upset protein metabolism is manifested by the inhibited synthesis of protein. Clinically it is manifested by formation of trophic ulcers and slow healing of wounds.

Disorders of fat metabolism are delayed formation of higher fatty acids and neutral fats from carbohydrates, and ample supply of free fatty acids to the blood. Clinically this is manifested by wasting of the patient. Fat in­filtration of the liver is the sign of upset fat metabolism. A severe disorder in fat metabolism is ketosis. This is an accumulation in the blood of acetone bodies and ketones (/3-hydroxybutyric acid, acetoacetic acid, acetone) which are intermediate products of oxidation of higher fatty acids in the liver. Diabetic coma, a fatal complication of diabetes mellitus, can develop in this disorder of fat metabolism.

Polyuria, loss of sodium and partially of potassium are symptoms of upset water-salt metabolism in diabetes mellitus. The pathogenesis of polyuria is associated with glycosuria which elevates osmotic pressure in the tubules to decrease reabsorption of water. Reabsorption of sodium in the kidneys is also decreased.

A long-standing and incompletely compensated diabetes mellitus results in vascular changes (retinopathy, nephropathy, or Kimmelstiel-Wilson syndrome) and atherosclerosis. Pronounced fluctuations in the blood sugar increase pituitary activity, cause spastic atonia of the vessels, which, in turn, affects the structure of their walls, accelerates the destruc­tion of elastic fibres, and promotes sclerosis and calcinosis.

Insulin deficit inhibits phosphorylation of vitamin B₆ which often causes neuropathic complications of diabetes mellitus.

Pathological anatomy. Diabetes mellitus is responsible for the decreased number of beta cells of the pancreatic islets, for their degranulation and hydropic degeneration. Hyaline and fat may be deposited in beta cells. This is not however a specific symptom of diabetes mellitus. At early stages of the disease, especially in young persons, morphological changes in these cells are absent.

Clinical picture. The symptoms of diabetes mellitus are excessive thirst (polydipsia), increased appetite, polyuria, hyperglycaemia, glycosuria, wasting, weakness, decreased work capacity, and skin itching, especially in the perineal region.

Inspection of the patient reveals rubeosis (reddening of the face, the cheeks, supraciliary arches, and the chin due to dilated cutaneous vessels) and xanthosis (yellowish decolouration of the palms and soles associated with upset conversion of carotin into vitamin A in the liver and accumula-

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Chapter 10. Endocrine System and Metabolism

tion of carotin in the skin). The patient's skin is dry, rough, easily scaling, covered with traces of scratching (due to skin itching). Furuncles, ex-ematous and ulcerous lesions can also be found. At points of insulin injec­tion, there are zones where fat is absent (insulin lipodystrophy).

Muscles and bones. Muscular atrophy and osteoporosis are observed in decompensated diabetes mellitus.

Cardiovascular system. Atherosclerosis of various arteries with the cor­responding clinical symptoms, angina pectoris, gangrene of the feet, etc. is not infrequent.

Respiratory organs. Diabetes mellitus often concurs with bronchitis, pneumonia, and pulmonary tuberculosis.

Gastro-intestinal tract. Mouth mucosa and the tongue are dry. Paradontosis and pyorrhoea frequently occur. Appetite is very good and sometimes voracious (bulimia). Study of the gastric juice reveals the presence of hypo- or achlorhydria. Fat dystrophy of the liver and its cir­rhosis develop in some patients with long-standing decompensated diabetes mellitus.

Kidney diseases. Arteriolosclerosis of the kidneys and intracapillary glomerulosclerosis (Kimmelstiel-Wilson syndrome) may occur. They are manifested by hypertension, retinopathy, and albuminuria. Pyelonephritis is not infrequent.

Retinopathy. Retinopathy in diabetes mellitus is manifested by the presence of exudate in the retina, haemorrhages, and pigment abnormality in the yellow spot. Cataracts often occur.

Changes in the nervous system. Polyneuritis is frequent. Headache, deranged sleep, and decreased work capacity are the symptoms of affection of the central nervous system.

The main laboratory methods used to diagnose diabetes mellitus and assess its gravity are based on determination of sugar and ketone bodies in the urine, determination of sugar in the blood on a fasting stomach and during the day, and glucose tolerance tests.

When a patient suspected for diabetes mellitus is examined, his blood and urine are in the first instance tested for sugar. Sugar in the urine of a diabetes mellitus patient may be 5-8 per cent and more. Morning urine of patients with latent diabetes mellitus may be free from sugar, and daily urine should therefore be better studied. Urine taken after giving the pa­tient a test meal or sugar can also be studied.

Blood of a healthy individual (with a fasting stomach) contains 4.4—6.6 mmol/1 (80-120 mg/100 ml) of glucose. This concentration increases to 28-44 mmol/1 (500-800 mg/100 ml) and more in diabetes mellitus pa­tients. But in the mild forms of the disease the blood sugar may remain normal (especially so if the test is done on a fasting stomach). In such cases

blood sugar should be determined 3 or 4 times a day with a normal diet given. If glycaemia appears to exceed normal in repeated glucose tolerance tests, the diagnosis of diabetes mellitus can be considered proved. After determining blood sugar on a fasting stomach, the patient is given to drink 50 g of glucose in 200 ml of water. Blood specimens are then taken at 30-minute intervals for 3 hours. The blood sugar in a healthy individual in­creases by about 50 per cent (but not over 9.4 mmol/1 or 170 mg/100 ml) during the first hour, while during the second hour the initial blood level is restored (or it may drop below normal). The rise in the blood sugar is higher in diabetes mellitus patients, the increase in sugar concentration is delayed, while the initial level is not restored even in three hours. There is a variant of the glucose tolerance test in which another portion of glucose is given to the patient in one hour following the first dose. The first glucose dose intensifies the secretion of insulin in healthy persons, and the second dose does not therefore increase the sugar concentration in the blood, while sugar curve of diabetes mellitus patients gives another ascent (two-peak curve).

Glucose oxidase and Samogyi-Nelson tests are now used for determin­ing blood sugar. The glucose oxidase method is used to determine true glucose of the blood and it is therefore most specific, but the normal glucose level is slightly underestimated compared with the Hagerdon and Jensen method (3.3-5.5 mmol/1, or 60-100 mg/100 ml). The sugar con­centration in the blood depends also on the technique by which the blood specimen is taken: glucose level is higher in capillary than in the venous blood. Increased blood sugar does not always indicate diabetes mellitus since it may be the result of emotional excitation. Glucosuria is an indirect sign of hyperglycaemia. The presence of sugar in the urine in the absence of hyperglycaemia cannot be used as an evidence of diabetes mellitus either, since glucosuria can be due to decreased sugar permeability of the kidneys (renal threshold). In the presence of kidney pathology (nephrosclerosis), glucosuria may be absent even when the blood sugar is abnormally high.

Tests for urine sugar are qualitative and quantitative. Sugar can be determined in the urine by special indicator papers (glucotest) and tablets (for rapid determination of urine sugar). Determination of acetone and acetoacetic acid (acetone bodies) is obligatory. It should however be remembered that acetonuria can occur also in healthy individuals during fasting and in toxaemia of pregnancy.

Patients with clear signs of diabetes mellitus do not require glucose tolerance testing. Prednisolone or corticoglucose test should be carried out in persons predisposed to diabetes mellitus and with normal results of glucose tolerance test. The results of glucose tolerance test depend on various factors: fasting, pathological processes in the liver parenchyma, in-

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juries, infections, acute disorders in cerebral circulation, and strong emo­tions.

Determination of the alkali reserve of the blood helps predict the ap­proaching grave complication of diabetes mellitus, i.e. diabetic coma. The alkali reserve decreases sharply in moderate acidosis. It decreases not only in diabetes mellitus but also in acidosis of other aetiology, e.g. in fasting or in kidney diseases.

Course. The onset of the disease may be acute or gradual. The first signs of diabetes mellitus may be persistent itching and furunculosis. By the course and severity of the symptoms, and also by the body response to the therapy given, the clinical picture of diabetes mellitus is differentiated into light, moderate, and grave. The degree of hyperglycaemia, glycosuria, the presence of ketone bodies in the urine, and the gravity of acidosis should also be taken into consideration. In addition to the mentioned forms of diabetes mellitus, the following three stages are distinguished in its course: prediabetes, masked diabetes, and true diabetes mellitus. Prediabetes can­not be diagnosed by the existing methods. This can be defined as hereditary predisposition, obesity, and cases where newborns (both dead and alive) weigh over 4.5 kg. Masked diabetes mellitus can be detected by the glucose tolerance test. True diabetes mellitus is diagnosed by clinico-laboratory findings.

Diabetic coma is a grave and sometimes fatal complication of diabetes mellitus. It occurs if diabetes mellitus is treated improperly or if the disease is complicated by acute infections, injuries, or nervous stress. Toxic symp­toms develop gradually in most cases and the onset of coma is preceded by its precursors (precomatose state). Excessive thirst develops along with polyuria, epigastric pain, dyspepsia, headache, and loss of appetite. The patient's breath smells of acetone (odour of rotten apples). Precomatose state is followed by the first phase of coma which is characterized (in addi­tion to the mentioned symptoms which are gradually intensified) by a strong nervous excitement: insomnia, restlessness, clonic convulsions, and Kussmaul's respiration. The excitement is followed by a marked inhibition, the second phase of diabetic coma: the patient develops dizziness, shows no interest in surroundings, and finally loses consciousness. When in a deep coma, the patient is motionless, the face may be pink or pallid, the skin dry, the muscle tone and tendon reflexes are decreased, pathological reflexes sometimes develop, the eyeball tone decreases, the eyeballs are soft to the touch, the pupils are narrow. Kussmaul's respiration is heard at a considerable distance. The pulse is low and fast; the arterial pressure falls. Hypothermia, oliguria, and sometimes anuria develop. Blood sugar markedly increases (from 22 to 55 mmol/1 or from 400 to 1000 mg/100 ml). The alkali reserve of blood decreases to 15-30 per cent

(v/v), the number of ketone bodies increases along with increased content of non-protein (residual) nitrogen; the chloride content decreases. Leucocytosis in coma can be as high as 50 x 10⁹ per 1 1 of blood with a neutrophilic shift to the left. Ketone bodies and considerable amounts of sugar are found in the urine. But gradual development of diabetic coma and distinct stages of this process are not always observed, and the terminal phase of diabetic coma may come suddenly, without precursors.

The pathogenesis of diabetic coma is associated with acidosis mainly on account of accumulation of ketone bodies and their toxic effect on the cen­tral nervous system.

Hypoglycaemic coma arises in patients treated with insulin for diabetes mellitus, if their diet lacks carbohydrates or as a result of insulin over-dosage. Hypoglycaemic coma develops rapidly, sometimes within a few minutes. Coma is preceded by a sudden feeling of hunger, weakness, sweating, tremor in the entire body, psychic and motor excitement. Com­atose state is characterized by pallor and moist skin, increased muscular tone and tendon reflexes, and convulsions; the pupils are dilated, the eyeballs remain firm. The blood sugar is low; sugar and acetone are absent from the urine. The patient quickly responds to treatment: after an in­travenous infusion of a hypertonic solution of glucose, the patient quickly regains consciousness.

Treatment. In the absence of malnutrition, ketosis, or concomitant diseases, and if there were no precomatose or comatose state, the patient may be given a diet therapy alone. Otherwise, and also if the antidiabetic preparations prove ineffective, or else if there are contraindications to their use, the patient should be given insulin.

The dose of insulin to treat diabetic coma depends on the gravity of the patient's condition and the length of the disease. In order to prevent the development of hypoglycaemic coma, a glucose solution in a hypertonic sodium chloride solution should be administered by drop infusion in 90—120 minutes following the administration of insulin.

Obesity

Obesity (adiposis) is excessive deposition of fat in subcutaneous and other tissues, which is associated with metabolic disorders.

Aetiology. Overeating is the main aetiological factor. Hypodynamia, hereditary and constitutional predisposition are also important. Pregnan­cy, lactation, and menopause are among other factors responsible for obesity in women.

Obesity can be regarded as an independent disease in cases with an ex­cessive caloric intake (alimentary obesity). Obesity can also be a symptom

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of endocrine diseases (thyroid or pituitary dysfunction) or diseases of the central nervous system (infection, injury, tumour).

Pathogenesis. The main pathogenic mechanism of obesity is dysfunc­tion of the central nervous mechanisms, i.e. the cerebral cortex and hypothalamic centres (the ventromedial and ventrolateral nuclei of the hypothalamus) that regulate fat and carbohydrate metabolism. The result of these disorders is upset equilibrium between the caloric intake and the amount of energy spent by a living body. The role of the endocrine factors and also changes in the local tissue metabolism with increased deposition of fat should also be considered in various types of obesity. Changes in in­sulin content in obese individuals are of special practical interest: at the early stage of obesity, these patients have hyperinsulinism, which is follow­ed by hypoinsulinaemia on account of exhaustion of the insular apparatus in long-standing obesity. Hypoinsulinaemia impairs tolerance to car­bohydrates which occurs in most obese persons, and often causes diabetes mellitus. Obesity can thus be regarded as prediabetes.

Pathological anatomy. Fat deposition is more pronounced in subcutaneous tissue, omen-tum, around the kidneys, and in the mediastinum. In the epicardium, fat is mainly deposited at the apex of the heart and around its right chambers. Fat can grow into the depth of the heart to separate muscle fibres, which thus grow thinner. The liver is enlarged at the expense of fatty (adipose) infiltration, which also affects the pancreas. Fat loosens the pancreatic parenchyma and causes atrophy of pancreatic islets.

Classification. Two types of obesity are distinguished, primary and secondary. Primary obesity includes alimentary obesity whose primary pathogenetic factors are unknown. Secondary obesity includes the follow­ing forms: (a) cerebral (hypothalamic obesity due to affection of the cen­tral nervous system, e.g. by a tumour, infection, or injury); and (b) en­docrine obesity which is connected with dysfunction of the pituitary and thyroid glands, or the ovaries.

There is a type of obesity in which fat is deposited in tender tumour-like growths (lipomatosis).

Clinical picture. The clinical picture of obesity is quite varied, depen­ding on the degree of the condition, length of a pathological process, and the presence of changes in other organs and systems.

The degree of obesity is determined by Broca's formula (weight of in­dividual = height - 100). The obesity is first degree if the patient's weight exceeds that calculated from the formula by 30 per cent; the second degree—from 30 to 50 per cent; the third degree—from 50 to 100 per cent; and the fourth degree of obesity is characterized by more than 100 per cent excess in weight. Individuals with the first and second degree of obesity do not complain of their disease. They attend the doctor only for aesthetic consideration. Patients with obesity of the third and fourth degree com-

plain of dyspnoea (which develops first under considerable load and later during light exercise), fatigue, impaired memory, hyperhidrosis, flaccidity, constipation, and menstrual disorders. General inspection of the patient alone is enough to establish the diagnosis of obesity. The colour of the skin may be normal; the skin can also be pallid or hyperaemic. White, red, or violet stripes (striae) can be seen on the skin of the abdomen and the thighs. Sometimes the skin sags together with the subcutaneous fat to resemble an apron. Because of hyperhidrosis, obese patients often have skin diseases, such as eczema, pyodermia, and furunculosis. The diaphragm is high and for this reason obese patients often develop bronchitis and pneumonia.

Long-standing and pronounced obesity provokes changes in the car­diovascular system. Hypertension and atherosclerosis are frequent. These pathological changes and also mechanical factors (accumulation of fat in the mediastinum, decreased respiratory excursions, high diaphragm) in­terfere with normal work of the heart and cause chronic circulatory insuffi­ciency.

Patients with obesity have increased appetite. They develop tendency to constipation and meteorism. Cholelithiasis, cholecystitis, cholangitis, and acute pancreatitis occur in obese patients more frequently than in nor-mosthenic individuals. Sex and pancreatic function decreases in obesity.

Treatment. Low-calorie diet is recommended to decrease the weight of obese patients to the normal level, after which the diet should be normaliz­ed. The meals should be taken at regular intervals; the patient should lead an active life (remedial exercises). Treatment of obesity by starvation or by decreasing significantly the ration is not recommended on account of possi­ble serious disorders.

Preparations decreasing appetite (anorexigenics) should be given to pa­tients on a fasting diet who suffer severely from hunger.

Prophylaxis. Health education and sports are effective.

Vitamin Deficiency

Vitamins are low-molecular chemical compounds contained in foods. They are necessary to maintain biocatalysis of separate biochemical and physiological processes in a living body. Vitamins are synthesized in man and animals in insufficient quantity and therefore they should be taken with food.

If food lacks vitamins, its assimilation is disordered and symptoms of vitamin deficiency develop. Pathological conditions occurring in full absence of vitamins are called avitaminosis. Types of avitaminosis depend on the lack of a particular vitamin (e.g. vitamin A, B_p B₂, etc.) and are designated avitaminosis A, avitaminosis B_lt etc., respectively. If deficiency

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of vitamins is only partial, this condition is called hypovitaminosis, the in­sufficiency is usually functional.

Aetiology and pathogenesis. Depending on the cause of vitamin defi­ciency, two forms are distinguished: exogenous and endogenous. Ex­ogenous or primary vitamin deficiency is caused by the low vitamin content of food. This is primary vitamin deficiency which develops in monotonous and irregular meals and unbalanced diet (with prevalence of car­bohydrates, small amounts of animal proteins and fats, and in the absence of fresh vegetables and fruits).

Exogenous or secondary vitamin deficiency is caused by various fac­tors. These may be disordered absorption of vitamins in the gastro­intestinal tract (alimentary diseases), in helminthiasis, acute and chronic liver diseases, malignant newgrowths, leucoses, familial enzymopathies, endocrine dysfunction (thyroid or pituitary dysfunction), ingestion of foods containing antivitamin properties (thiaminase, avidin, etc.). Vitamin deficiency can develop in prolonged use of medicinal preparations with an­tivitamin properties (streptomycin, chloramphenicol, sulpha drugs, etc.). Vitamin deficiency can arise with adequate intake of vitamins but in the presence of increased demands for these substances, for example at high or low ambient temperature, during intense exercise, nervous or psychic overstrain, and in oxygen deficiency.

Demands in vitamins, especially for ascorbic acid, pyridoxine, folic acid, calcipherols, and tocopherols especially increase in pregnancy and nursing. Vitamin deficiency can develop also in prolonged use of a diet lacking vegetables, fruits, rye bread, etc. Avitaminosis develops during wars and other disasters, in long sea voyages, in polar regions where people feed on dry or canned foods, etc. Beri-beri (Bj avitaminosis), pellagra (PP avitaminosis), scorbutus (scurvy, or C avitaminosis) occur now in develop­ing countries of Asia, Africa and South America. Population in developed countries usually suffers from hypovitaminosis, which arises due to im­proper storage of foods, seasonal variations in vitamin content of foods, or incorrect processing of foods.

Clinical picture. Pure hypovitaminosis occurs comparatively rarely. More frequent are deficiencies of various vitamins, with prevalence of symptoms characteristic for the lack of a particular vitamin. General vitamin deficiency develops in practically healthy individuals early in spring and it is manifested by rapid fatigue, decreased work capacity, poor appetite, and deranged sleep. Table 5 gives clinical signs of separate hypovitaminoses in deficit of separate vitamins. Diagnosis of avitaminosis (in the presence of specific pathological symptoms) can be confirmed by testing the blood and urine for the presence of vitamins or their metabolites. Biochemical tests are also used to obtain indirect evidence of

Table 5

Main Clinical Symptoms of Diseases in Vitamin Deficiency

vitamin metabolic disorders. For example, tryptophan is given to a patient and excretion of xanthurenic acid in the urine is determined. This gives in­formation of the pyridoxine supply of the body.

Determination of eye sensitivity to light helps establish deficiency of retinol and riboflavin. Immunobiological tests are also used: phagocytic reaction, complementary activity test, gamma-globulin concentration test, etc.

Radio-indicative method is also used to determine vitamin deficiency. It can be used to determine distribution, transport, conversion, and excretion of vitamins.

Special Part

Treatment. Diet containing much vitamins and vitamin preparations (in doses several times exceeding normal daily demands) should be prescribed. Hypervitaminosis and toxic complications are however possible in prolong­ed therapy.

Prophylaxis. Health education of population is important. People should be taught to feed properly, and instructions should be given how to cook and store foods. General knowledge of vitaminology is useful. Special measures must be taken by the appropriate governmental institu­tions. These measures include increased production of foods rich in vitamins, and of preparations (vitamins and polyvitamins). Foods for sale should be stored and processed properly at public catering enterprises. Vitamin content of food should be increased by selection of agricultural crops and rational animal breeding.

Chapter 11.