Main symptoms and syndromes in anaemias. Complete blood count. Hemorrhagic diateses.

Main symptoms and syndromes in anaemias. Complete blood count. Hemorrhagic diateses.

Main symptoms and syndromes in diseases of endocrine system – diabetes mellitus, pathology of a thyroid gland. Allergy.

Main symptoms and syndromes in diseases of musculosceletal apparatus

 

DISEASES OF THE BLOOD

Anaemia

Anaemia is a pathological condition characterized by decreased numb of erythrocytes and/or haemoglobin content in a blood unit volume due their general deficiency (Gk an not, haemia blood, i.e. deficient of blood.

Anaemia should be differentiated from hydraemia (abnormally wate d) in which the erythrocyte and haemoglobin are deficient as well, but at the expense of their absolute reduction but due to dilution of blood enal, cardiac and other oedema. Anaemia should also be differentiated noligohaemia, which is the reduction of the total volume of blood, e.g. nediately after a profuse haemorrhage. The total mass of circulating od can be normal in anaemia (normovolaemia), increased (hyperemia) or decreased (oligohaemia or hypovolaemia). Thickening of od in persistent vomiting and profuse diarrhoea can mask anaemia ause the total amount of plasma decreases and the number of throcytes and haemoglobin in a unit volume of the circulating blood can normal or even increased.

Anaemia is often characterized not only by quantitative changes in the i blood composition, but also qualitative changes in the structure of throcytes and haemoglobin molecules. These changes are important for : transport function of blood and tissue respiration, and can be the cause additional pathological changes in the body. For example, a congenital feet of erythrocytes in some hereditary haemolytic anaemia may (due to ;ir intense haemolysis) cause haemosiderosis of the internal organs, for-ition of pigment stones in the gall bladder, etc.

           Anaemia has a pronounced effect on the vital activity of the body, memization causes oxygen hunger of organs and tissues (hypoxia) and :ir dystrophy. For example, if the blood haemoglobin content is halved 3-80 g/1), initial symptoms of myocardial dystrophy develop. If the k emoglobin content decreases to 50 g/1, the dystrophic changes become onounced. Unoxidized products of metabolism (lactic acid, in the first stance) accumulate in the body due to hypoxia. The alkaline reserve of ood decreases. In grave cases, a tendency to acidosis develops which uses further dystrophy of tissues. Severe anaemias attended by marked sorders in tissue metabolism are incompatible with life.

Anaemia of any origin is accompanied by some compensatory~pro-:sses, which partly remove or lessen its consequences: (1) blood circula-un is intensified, i.e. stroke and minute volumes increase, tachycardia svelops, and the rate of blood flow increases; (2) blood distribution is itered, blood depots in the liver, spleen, and muscles are activated, and ie blood supply to the peripheral tissues becomes limited at the expense of le increased blood supply to the vital organs; (3) oxygen utilization in ssues is intensified and the role of anaerobic processes in tissue respiration rcreases (anaerobic respiration with glutathione); (4) the erythropoietic unction of bone marrow is stimulated. More than 50 types of anaemia are now differentiated. According  to  their  origin,  the  following  types  of anaemia are listinguished.

1.Anaemia due to loss of blood (acute and chronic).

2. Anaemia due to disordered haemopoiesis in deficiency of iron (necessary for the production of haemoglobin), in vitamin B₁₂ deficien­cy (necessary for normal erythropoiesis), in inhibition of the bone marrow by endogenous or exogenous toxicosis, radiation, or by some unknown factors, and also in cases where red bone marrow is replaced by other tissue, e.g. myeloma or multiple metastases.

3. Anaemia due to excessive haemolysis. This type of anaemia is sub­divided into: (a) anaemia with prevalent extravascular (intracorpuscular) haemolysis of erythrocytes in macrophages of the spleen, and, to a lesser extent, in the bone marrow and liver. These are anaemia caused by hereditary morphological and functional erythrocyte deficiency (spherocytic and ovalocytic anaemia), and auto-immune haemolytic anaemia. They are all characterized by hyperbilirubinaemia and splenomegaly; (b) anaemia with intravascular, usually acute haemolysis (in various poisoning, transfusion of incompatible blood, cold and effort anaemia) attended by release into the plasma of unbound haemoglobin and by haemoglobinuria^, haemosiderosis of the internal organs is observed also in chronic haemolysis (e.g. in Marchiafava-Micheli disease). This classification is only conventional because both intracorpuscular and vascular haemolysis can occur in one and the same form of haemolytic anaemia.

Haemolytic anaemia is also often subdivided as follows: (a) hereditary (congenital) anaemia, which includes membranopathy of erythrocytes (associated with abnormality of protein or lipid complexes of erythrocyte envelope, causnift changes in their shape at I premature decomposition; microspherocytic anaemia, ovalocytic ana mia, etc.); enzymopenic anaemia (due to deficiency of various enzyme systems of erythrocytes, which promotes their accelerated decomposition) and haemoglobinopathy in which the structure of haemoglobin or its synthesis are disturbed (sickle-cell anaemia, thalassaemia); (b) acquired anaemia (auto-immune haemolytic and iso-immune anaemia, and also anaemia caused by Vnechanical injury to erythrocytes, acquired membranopathies, toxic anaemia, etc.).

Apart from the pathogenetic classification, there are classifications based on other principles. Three groups of anaemia, for example, are distinguished in accordance with haemoglobin saturation of erythrocytes (by the colour index): normochromic (0.8-1.0), hypochromic (less than 0.8) and hyperchromic anaemia (more than 1.0). The group of hypochromic anaemia includes iron-deficiency anaemia: chronic (less acute) posthaemorrhagic anaemia, gastrogenic iron-deficiency anaemia, and juvenile chlorosis. Hyperchromic anaemia is caused by the deficiency of vitamin B₁₂. This is Addison-Biermer anaemia, bothriocephalus anaemia, and also achrestic anaemia (due to defective utilization of Vitamin B₁₂). Other anaemias proceed without considerable changes in the colour index of blood and are therefore normochromic.

It is very important to assess the regenerative capacity of the bone mar­row upon which (to a certain degree) depend treatment and prognosis of the diseases. Distinguished are regenerative anaemia, i.e. anaemia in which the bone marrow preserves its capacity to produce new erythrocytes; hyporegenerative anaemia, in which this capacity is impaired; and aregenerative or aplastic anaemia, in which bone marrow function is comV pletely or almost completely lost. The regenerative function of the bone, marrow is assessed by the rate at which the quantity of reticulocytes increases in the peripheral blood and by the proportion of the erythro- and leucoblastic elements in the sternal punctate. Their normal ratio is 1:3 or 1:4, while in regenerative anaemia, in which erythropoiesis dominates in the compensatory function of the bone marrow, this ratio becomes 1:1, 2:1 and even higher. This shift is absent in hypo- or aregenerative anaemia, while the reticulo; le content of the peripheral blood is low.

 

ACUTE POSTHEMORRHAGIC ANAEMIA

Anaemia caused by an acute blood loss (acute posthaemorrhagic anaemia) occurs mostly in various injuries associated with traumatized large vessels (extrauterine pregnancy, delayed placental detachment during labour, etc.). Acute posthaemorrhagic anaemia occurs in diseases that can be attended by profuse bleeding, e.g. in gastric and duodenal ulcer, degrading tumour of the stomach, kidneys, or the lung, in tuberculosis and abscess of the lung, bronchiectasis, varicose dilation of the oesophageal veins in liver cirrhosis, haemorrhagic diathesis, and especially in haemophilia. 

Clinical picture. In cases w)th external haemorrhage, the physician can often locate the source of bleeding at first sight (e.g. in injury). The patient’s grave condition can in these cases be directly attributed to profuse bloefd loss. Haemorrhage from the internal organs can be manifested by blood vomiting (unaltered blood originates from the oesophagus; brown blood from the stomach), by expectoration of blood (scarlet foaming liquid), by the presence of blood in faeces (melaena in haemorrhage from the stomach or the small intestine; dark or scarlet blood originates from the large intestine, especially from its terminal part) and by blood presence in the urine (haematuria). It should be remembered that in gastro-intestinal haemorrhage, the blood can only be discharged into the environment in a.certain lapse of time (with the vomit or excretions). Moreover, haemorrhage caused by the rupture of the spleen, liver, or by the internal injury to the chest can be difficult to establish because blood will ac­cumulate in the abdominal or pleural cavity.

The first sign of a sudden haemorrhage is the feeling of weakness, dizziness, noise in the ears, palpitation of the heart, nausea, and in rare cases vomiturition. In severe cases with pro-» fuse blood loss, the patient is in the state of shock (if the bleeding is caused by an injury) or collapse (if haemorrhage is due to affection of the internal organs). The patient’s condition depends not only on the amount of blood loss, but also on the rate at which blood is lost. In­spection reveals pronounced and in some cases deadly pallidness; the skin is covered with sticky cold sweat, the skin temperature is subnormal. Respiration is superficial and ac celerated. The pulse is fast, small, and (in severe cases) thready. Arterial pressure (both systolic and diastolic) is low. Auscultation of the heart reveals marked tachycardia.

The pathological and compensatory changes in acute blood loss with benign outcome can be divided into three stages (or phases). First oligohaemia develops. It causes a reflex spasm o the vessels to decrease the volume of the vascular system and to recover blood from it reserves (depots). For this reason, the blood haemoglobin and erythrocyte content may re maiormal within the first hours (or even within 1 or 1.5 days) following the blood loss Tissue fluids are drawn into the vessels to cause hydraemia in 2 or 3 days: the erythrocyte an haemoglobin content in unit volume decreases. Signs of marked activation of erythropoiesi appear on the third to seventh day. Anaemia becomes hypochromic in the loss of considerabl amount of blood due to exhaustion of the iron store.

Treatment. Bleeding should be arrested as soon as possible by placing a tourniquet or by tamponade of the external haemorrhages in wounds. Surgical intervention is indicated in coi tir.uing haemorrhage from the internal organs. Measures to prevent shock or collapse shoul alsotre taken. Blood loss should be compensated for by infusion of whole blood or i substitutes; cardiac and vascular medicinal preparations should be administered. Ire preparations should be given to patients with profuse blood loss in several days after tl haemorrhage has been arrested.

IRON DEFICIENCY ANAEMIA

Iron deficiency anaemia (anaemia sideropriva gastroenterogenic arises in the deficit of iron which is necessary for the production < haemoglobin in erythrocytes. This type of anaemia develops in patien with decreased iron absorption due to resection of the stomach (“agastr anaemia”), removal of a considerable part of the small intestine, especial of its proximal part, in intestinal diseases attended by abnormal absor tion, and in the iron deficit in food. The latter occurs mostly in childr with prolonged milk diet and copper deficit. Increased iron demands occ during intense growth of the body. During establishment of the menstrt cycle in young girls (menstrual loss of blood and iron ions) juvenile in deficiency anaemia (juvenile chlorosis) may develop. Chronic haemorrha also causes iron deficiency anaemia.

Repeated (not profuse) loss of blood cause anaemization due to exhaustion of the ii store which is necessary for the production of haemoglobin in erythrocytes. Daily intake iron with food is small, about 11-28 mg, and one fourth of this quantity is only absorb This is equivalent to the iron content of 15 ml of blood. Daily loss of 15 ml (or even sina amount) of blood therefore inevitably exhausts the iron store to cause iron deficie anaemia.

Chronic blood loss and chronic posthaemorrhagic anaemia atter many diseases of the internal organs, and in the first instance, of I gastro-intestinal tract. In most cases these are gastric or duodenal ulc cancer, polyposis of the stomach and intestine, haemorrhoids, and cert: types of helminthiasis. Chronic posthaemorrhagic anaemia often occurs tumours of the kidneys, cavernous tuberculosis of the lungs, and in uterine haemorrhage.

Some other factors promote anaemia. These are mainly those factors which can decrease the iron stores of the body. For example, patients with secondary gastric hyposecretion and enteritis develop anaemia sooner and it runs a more severe course in the presence of even insignificant chronic haemorrhage. Gravity of chronic posthaemorrhagic anaemia arising in pa­tients with degrading tumours of the gastro-intestinal tract, kidney, or the uterus, is intensified by the toxic effect of the tumour on the haemopoiesis and by multiple metastases into the bone marrow, etc. Hydrochloric acid of the gastric juice promotes reduction of trivalent iron to its divalent form, which is easier assimilated. But recent studies show that hydrochloric acid does not play a decisive role in activation of iron absorption.

In the absence of adequate iron supply to the body or its utilization from the store, the synthesis of haemoglobin, myoglobin, and iron-containing enzymes of various cells involved in the oxidation processes is upset. This impairs nutrition of tissues and accounts for the development of many symptoms of the disease. The clinical picture of iron deficiency anaemia is explained by insufficient oxygen transport to tissues due to anaemia on the one hand, and by disordered cell respiration on the other.

Clinical picture. Slow development (within months, and years) of iron deficiency anaemia accounts for actuation of the compensatory mechanisms. Most patients therefore are well adapted to the disease and can satisfactorily stand even significant anaemia.

We shall not discuss patient’s complaints associated with the main disease, to which anaemia is secondary (e.g. the cause of chronic haemorrhage). The specific complaints of anaemic patieqts will only be emphasized: weakness, dizziness, dyspnoea (especially exertional), increased fatigue, noise in the ears, and fainting. Many patients develop various dyspeptic symptoms: decreased appetite, perverted taste, slight nausea, heaviness in the epigastrium after meals, and regurgitation. Diarrhoea is also frequent. Slight paraesthesia (tinging and pricking) is possible. Excruciating dysphagia sometimes develops during swallowing dry or solid food in especially severe cases. This sideropenic dysphagia was first described by Rossolimo and Bekhterev in 1900-1901. Later this syndrome was described by Plummer and Vinson. The dysphagia is explained by ex­tension of the atrophic process from the stomach onto the oesophageal mucosa, and sometimes by its development in the proximal part of the soft connective-tissue membranes and bridges.

Inspection of the patient reveals pallor.

Pallor of conjunctiva in anaemia

 

 

Pallor of nail beds in anaemia

 

Certain trophic changes in the skin, its appendages, and mucosa can be due to the general iron deficit. The skin is dry and sometimes slightly scaling. The hair is brittle, early grey, and showing the tendency to falling. The nails become flat, sometimes spoon-like, opaque, marked by transverse folds, and brittle (koilonychia). The mouth angles often have fissures (angular stomatitis), the papillae of the tongue are levelled (atrophic glossitis). Theteeth lose their luster and quickly decompose despite a thorough care. If iron preparations are taken for a long time, the teeth may blacken due to forma­tion of black iron sulphite (by the reaction of iron with hydrogen sulphide which is liberated by the carious teeth). Purulent inflammation of the gum mucosa around the tooth necks develops (alveolar pyorrhoea).

Physical examination can reveal a slight indistinct enlargement of the left ventricle, systolic murmur at the heart apex, and nun’s murmur over the jugular vein (mostly on the right). Lymph nodes, liver and spleen are not enlarged.

Study of the blood reveals decreased erythrocyte and even more decreased haemoglobin content oflthe blood. The colour index is less than 0.85; in grave cases it is 0.6-0.5, and even lower. Microscopy of blood (Plate 30) reveals pallid erythrocytes (hypochromia), anisocytosis, and poikilocytosis. The average diameter of erythrocytes is less thaormal (microcytosis). The number of reticulocytes is small. Anaemia is usually at­tended by thrombocytoleukopenia, sometimes relative monocytosis, lym­phocytosis, and eosinopenia. The iron content of the serum is decreased (1.5-2.5 times and more). The percentage of transferrin saturation also decreases below 15).

Hypochromic erythrocites

 

 

 

Microspherocites

 

Ovalocites

 

 

Reticulocites

 

Erythrocites in different types of anaemia

 

Decreased activity of the iron-containing nzyrnes of tissue respiration provokes (or intensifies) atrophy of the gas. o-intestinal mucosa. The study of gastric juice reveals in most cases achlorhydria or even achylia; the total amount of the excreted juice is much decreased. X-rays reveal levelled folds of the oesophageal and gastric mucosa. Oesophagoscopy and gastroscopy confirm atrophy of the oesophageal and gastric mucosa.

Course. The course of the disease is chronic and gradually progressive if the iron deficit in the body increases.

Treatment. Iron preparations (haemostimulin, etc.) are given. If the pa­tient has gastritis or peptic ulcer, the iron preparations should better be given intramuscularly or intravenously (ferbitol, fercoven, etc.). The therapy gives a comparatively rapid and permanent effect: work capacity is rapidly restored, erythrocyte and haemoglobin of blood normalize in 3-5 weeks. The patient should however be regularly (several times a year) given prophylactic courses of therapy with iron preparations in order to prevent possible relapses of the disease. The diet of patients with iron deficiency anaemia should be rich in iron salts, e.g. liver, meat, eggs, apples, dried fruits. Efficacy of treatment of anaemia caused by chronic loss of blood depends on removal of the source of blood loss

 

VITAMIN B₁₂ (FOLIC ACID) DEFICIENCY ANAEMIA

Aetiology and pathogenesis. Vitamin B₁₂ (folic acid) deficiency anaemia was first described by Addison in 1855. One of its forms was later given the name of Addison-Biermer anaemia. In 1868, Biermer published a more detailed description of the disease, which he called pernicious or malignant anaemia, because its prognosis was then grave and patients usually died in a few months or years after the appearance of the first symptoms.

The disease was effectively treated for the first time by Mindt and Murphy (1926). The patients were given raw calf liver in large amounts every \ day. Minot and Murphy noted that distinct remissions followed in patients who were given this diet and conjectured that raw liyer contained a certain substance which is necessary for normal haemopoiesis, and whose absence or deficit causes pernicious anaemia. The next stage in the study of this disease is connected with experiments carried out by Castle (1929). He noted that meat treated with gastric juice (containing various amounts of hydrochloric acid) produces an anti-anaemic effect when administered into the stomach of patie. s with the Addison-Biermer anaemia. Gastric juice alone, untreated meat, or meat treated with gastric juice of patients with the Addison-Biermer anaemia have no anti-anaemic effecff)Castle suggested that a special substance, haemopoietin, was necessary for normal maturation of erythrocytes. Haemopoietin is produced by combination of a certain extrinsic factor supplied with food and the intrinsic factor con­tained iormal gastric juice.

At the present time, Castle’s conjecture concerning the pathogenesis of Addison-Biermer anaemia has been proved experimentally and clinically. The extrinsic and intrinsic factors and their biological role have been studied sufficiently well. The factor is vitamin B₁₂ (cyanocobalamin) discovered by Smith in 1948 which is contained in calf liver, kidneys, meat, eggs, and gastromucoprotein produced by the accessory cells of the glands found in the fundus of the stomach. In healthy subjects, vitamin B₎₂ com­bines with gastromucoprotein in the stomach to give a sufficiently stable complex which protects vitamin B₁₂ from intestinal microflora to ensure adequate absorption of vitamin B₁₂ (mainly in the ileum). Gastromucopro­tein is absent from the gastric juice of patients with the Addison-Biermer anaemia due to pronounced atrophic gastritis. In the absence of gastromucoprotein, vitamin B₁₂ delivered with food is decomposed by in­testinal flora and is not assimilated by the body to cause vitamin B₁₂ deficit.An other cases, vitamin B₁₂ (folic acid) deficiency anaemia is the result of vast resection of the stomach, severe enteritis, increased demands for vitamin B ₂ in pregnancy, its consumption by helminths (bothriocephaliasis), and in disordered assimilation of this vitamin by the bone marrow (achrestic anaemia).

An important biological effect of vitamin B₁₂ is activation of folic acid. Like vitamin B., folic acid belongs to substances included in the group of vitamin B. It is contained in leaves oi various plants, fresh vegetables, beans, liver, and kidneys of animals. Folic acid is depositee in the human body mainly in the liver, where it is present in inactive state. Vitamin B₁₂ pro motes formation of folic acid derivatives, folates, which are probably the factor necessary foi haemopoiesis in the bone marrow. In conditions associated with vitamin B ₂ and folate defi ciency, the synthesis of DNA is disordered; this in turn causes disorders in cell division; tin cells become large and qualitatively inadequate. Erythroblasts are affected most severely large cells of embryonal haemopoiesis, megaloblasts, are found in the bone marrow instead o erythroblasts. They are not only larger than ery’hroblasts; they also differ in the structure o their nuclei and protoplasm, earlier and more intense saturation with haemoglobin durini their differentiation (at the stage of reticular structure of the nucleus), retarded mitotic divi sion, and mainly in their inability to grow to normal erythrocytes. Most megaloblasts ar decomposed in the bone mafrow before they reach the stage of a nucleated cell. Only a smal quantity of megaloblasts are differentiated to anuclear cells (megalocytes) and enter the blooi vessels. Megalocytes are large!” and more saturated with haemoglobin than erythrocytes differ from them by morphological and functional inadequacy. Megalocytes have no sue! high oxygen-transport capacity as the erythrocytes and are quickly decomposed by reticuloei¹ dothelial cells: the average life of megalocytes is about three times shorter than of erytrocytes.

The absence of gastromucoprotein in gastric juice (like achlorhydria which usually attend this disease) is due to atrophy of the gastric mucosa. Some investigators believe that atroph of gastric mucosa is not inflammatory in its origin as it was believed earlier (atrophic gastritii but is a result of congenital insufficiency of its glandular apparatus which is manifested wit time. In the opinion of other authors, the atrophy of gastric mucosa is caused by antibody produced by the patient’s body to the gastric glandular cells, which can however be slightly altered by toxic effects or inflammation (auto-immune mechanism).

If the second coenzyme of vitamin B12 desoxyadenosylcobalamin, is deficient, metabolism becomes upset with accumulation of methylmalonic acid, whicli is toxic for th nervous system (provokes funicular myelosis).

The Addison-Biermer anaemia attacks commonly the aged; offen among women is higher than in men.

Pathological anatomy. The skin and the organs are pallid. Small haemorrhages are poss ble. Haemosiderosis of the liver, kidneys, bone marrow and dystrophic changes in them ai characteristic. These changes are observed also in the myocardium, the brain, and the spin cord (mostly in the lateral cord). Bone marrow is affected by hyperplasia; it is bright-red, II foci of extramedullar haemopoiesis are seen in the spleen and the lymph nodes. Histologic studies show prevalence of red blood cells; many young forms, myeloblasts are seen Megaloblasts, the large cells of perverted erythropoiesis, are especially numerous.

Clinical picture. The onset of the disease is insidious. The patient grow weaker, he complains of heart palpitation, dizziness, and dyspnoe; especially during exercise or brisk movements; the work capacity is in paired, the appetite becomes poor; slight nausea is possible. The first con plaint is often the burning sensation in the tongue. This is explained by tr  development of atrophic glossitis (see below) which usually attends this disease. The patient often develops achylic diarrhoea or, on the contrary, persistent constipations. Dystrophic changes in the nervous system cause skin anaesthesia and paraesthesia; the gait is often affected in grave cases: spastic paresis develops (incomplete spastic paralysis of the lower ex­tremities); the knee reflex disappears, the function of the urinary bladder and the rectum can also be affected. All these symptoms are known as the funicular myelosis which develops due to the predominant affection of the lateral spinal columns. Symptoms of the disordered activity of the central nervous system (deranged sleep, emotional lability, etc.) become apparent. Inspection of the patient reveals pallor of the skin and mucosa, usually with a yellowish tint due to increased decomposition of megalocytes and  formation of bilirubin from the released haemoglobin, and a slight swelling of the face. The patient is not thin. Quite the reverse: most patients are well fed. The bright-red smooth and glossy tongue (because of the pronounced atrophy of the papillae) is quite characteristic of the Addison-Biermer anaemia.

 

 

 

 This symptom is known as Hunter’s glossitis (W. Hunter was the first to describe this symptom). The mouth mucosa and the posterior wall of the throat are also atrophied. The tip and edges of the tongue, and also the mouth mucosa can be ulcerated. The tendency to caries is often seen in the teeth.

Pressing or tapping on the flat and some tubular bones (especially the tibia) is often painful. This is the sign of bone marrow hyperplasia. Palpation can reveal a slight enlargement of the liver and the spleen.

The cardiovascular system is usually involved as well. The left border of the heart is displaced to the left, tachycardia develops, “anaemic” systolic murmur is heard at the heart apex in 75 per cent of cases; the nun’s mur­mur is often heard over the jugular veins.The pulse is soft and accelerated. Most patients develop hypotension. ECG shows ascertain decrease in the general voltage, the decreased T wave and the S-T interval.

Changes in the gastro-intestinal tract are pronounced. Especially characteristic is atrophy of gastric mucosa which can be revealed by X-ray examination, and more distinctly by gastroscopy. The atrophy is often focal, and the affected sites (mostly in the fundus of the stomach) can be seen as iridescent spots. Atrophy can combine with polyps in the folds of gastric mucosa and its polypous thickening. It should be remembered that anaemia, including pernicious anaemia, can be a symptom of a malignant tumour in the stomach. Cancer of the stomach occurs in patients with the Addison-Biermer anaemia 8 times more frequently than in healthy persons. Patients with this disease should therefore be systematically inspected by X-rays (by gastroscopy whenever possible). Almost all patients develop achlorhydria.   In  98  per  cent  of cases it  has the histamine-resistant haracter. The total amount of juice produced during the study is usually significantly diminished; the pepsin content of the juice is very low or it cannot be determined at all (achylia). Usually achlorhydria develops many years before the first symptoms of anaemia develop.

Elevated temperature is a common symptom of vitamin B₁₂ (folic acid) deficiency anaemia; the temperature is usually subfebrile.

Blood plasma contains slightly increased amounts of free bilirubin due to increased haemolysis of the red cells, especially megalocytes; the plasma iron content increased to 30-45 mmol/i (170-200 /tg/rnl).

The blood picture is characterized by a sharp decrease in the quantity of erythrocytes (to 0.80 x 10¹² at a comparatively high haemoglobin saturation. Despite the decreased total haemoglobin content of the blood, the colour index remains high (1.2-1.5). Red blood cells dif­fer in size (anisocytosis), with prevalence of large erythrocytes (macrocytes). Especially large slightly oval and intensely red megalocytes appear (in many cases megaloblasts are also seen). The volume of each cell increases. Many erythrocytes are oval, or they have the shape of a sickle and other shapes (poikilocytosis). Megalocytes often have remnants of the nucleus or its envelope in the form of Jolly bodies , Cabot rings. The con­tent of reticulocytes is not high. The number of reticulocytes sharply in­creases (reticulocyte crisis) during vitamin B₁₂ therapy to indicate the beginning remission. Blood leucocytes decrease mostly at the expense of neutrophils. Eosinopenia, relative lymphocytosis, and thrombocytopenia are observed. Large neutrophils with polysegmented nuclei also occur.

TheQuality of erythroid precursors in a specimen of bone marrow sharply increases, by 3—4 times compared with the number of leucopoietic cells (the proportion ^xbeing reverse in physiological conditions). Megaloblasts are observed in varying amounts among the erythroid precur­sors; in grave cases they are found in prevailing quantity. Both erythropoiesis and leucopoiesis are disordered. Megakaryocytes are also large, with a multi-lobed nucleus: thrombocyte separation is disordered.

 

 

 

Macrocites

 

 

Bone marrow in megaloblastic anaemia

 

Course. If untreated, the disease progresses. Before Minot and Murphy proposed their effective treatment of the disease, patients rarely survived more than 3 years. At the terminal period, many patients developed coma (coma perniciosum) with loss of consciousness, arephlexia, decreased arterial pressure and temperature, vomiting and involuntary urination.

At the present time the patient recovers from the Addison-Biermer anaemia if treated properly and if adequate prophylactic measures against relapses of the disease are taken.

Treatment. Vitamin B₁₂ is given. In most cases treatment begins with moderate doses of the vitamin (100-300 fig) which is given once a day in­tramuscularly or subcutaneously. Considerable shifts in the bone marrow _ate toward normalization of erythropoiesis are observed already in 24 hours vitamin is given. Cells produced by division and differentiation of juvenile forms are very much like the cells produced at the corresponding stages of normal erythropoiesis. Erythropoiesis normalize completely in 2 or 3 days. In 5 to 6 days of the therapy, the newly formed erythrocytes enter the blood vessels in considerable amounts: the reticulocyte crisis occurs. The number of reticulocytes in the peripheral blood increases to 20-30 per cent and then gradually decreases. General weaknessens, work capacity is regained, and gastric secretioor malizeS in certain cases.

Signs of funicular myelosis are eliminated much slower and do not always disappear completely. After the blood picture normalizes and the symptoms of the disease markedly subside, the patient is given maintenance therapy with small doses of vitamin B₁₂ (100 ng weekly, or 2-3 times a month). This therapy should be maintained for the rest of the patient’s life. Clinical blood counts should be done periodically.

 

Haemorrhagic Diathesis

Haemorrhagic diathesis is the disease characterized by the tendency to bleeding and repeated haemorrhages; they may occur spontaneously and may be caused by injuries; injury can be quite insignificant, which other­wise would never provoke bleeding in a normal individual.

Aetiology and pathogenesis. These are quite varied. Some types of haemorrhagic diathesis are hereditary but many of them can be caused by some external factors

Avitaminosis (deficit of vitamins C and P) is an especially predisposing factor. Some infections (long-standing sepsis, louse-born typhus, virus haemorrhagic fevers, icterohaemorrhagic leptospirosis), allergic condi­tions, some diseases of the liver, kidneys, and of the blood system can also provoke the onset of haemorrhagic diathesis.

Haemorrhagic diathesis can be classified by the pathogenesis into two major groups: (1) haemorrhagic diathesis due to disordered capillary permeability (haemorrhagic vasculitis, vitamin C deficiency, some infec­tious diseases, trophic disorders, etc.); (2) haemorrhagic diathesis due to disorders in the blood coagulation and anticoagulation system. The latter group is further subdivided into the following conditions:

          A. Haemorrhagic diathesis caused by disordered blood coagulation system:

(1)  first phase: congenital deficit of plasma components of thrombo-platelet formation (factors VIII, IX, XI), haemophilias A, B, C, etc.; deficit of thrombocyte components (thrombocytopathy, e.g. throm­bocytopenic purpura; see below);

(2)  second phase: deficit of plasma component of thrombin forma­tion—factors II, V, X, the presence of antagonists to them and of their inhibitors;

(3)  third phase: deficit of plasma components of fibrin formation-factors I (fibrinogen) and XII.

B. Haemorrhagic diathesis caused by accelerated fibrinolysis (due to in­ creased synthesis of plasmin and insufficient synthesis of antiplasmin).

C.  Haemorrhagic diathesis caused by disseminated intravascular coagulation (thrombohaemorrhagic syndrome or coagulopathy of consumption) in which all procoagulants are utilized during massive intravascular coagulation and the fibrinolysis system is activated.

This concise classification of haemorrhagic diathesis is only conventional because several pathogenic factors are often involved. This classification covers a very large group of diseases, both hereditary and acquired, and also secondary syndromes arising against the background of the main disease (metastasizing malignant tumour, burn disease, etc.)

Clinical picture. The general clinico-morphological symptoms of haemorrhagic diathesis are haemorrhages into various organs and tissues, external and internal haemorrhages (from the gastro-intestinal tract, lungs, uterus, kidneys, etc.) and secondary anaemization. The disease is com­plicated by dysfunction of the haemorrhage-affected organs, by hemiparesis in disordered cerebral circulation, regional paralysis and paresis in compression of large nervous trunks by haematomas, haemar-throsis in repeated haemorrhages into the joints, etc.

Despite the great variety of haemorrhagic diatheses and certain diagnostic difficulties, accurate diagnosis is quite important for efficacious therapy in each particular case. The aetiological and pathogenetic factors of the disease should be properly considered for anaccurate diagnosis.

 

 

Petechia

 

Ecchymoses

 

 

 

Haemorrhagic diathesmis the subject of special study of senior medical students. Here we shall only acquaint the reader in general with thrombocytopenic purpura (Werlhof’s disease).

 

 

Megacariocite

 

The prophylaxis of hereditary (familial) haemorrhagic diathesis in­cludes medico-genetic studies that may give the wife and husband the necessary information and advice concerning possible complications in their offspring; if haemorrhagic diathesis is not hereditary but acquired, measures should be taken to preclude development of diseases that may promote the onset of haemorrhagic diathesis.

Thrombocytopenic purpura (Werlhof’s disease). Thrombocytopenic purpura is a haemorrhagic diathesis due to the deficit of blood platelets. The disease was first described by Paul Werlhof in 1735. Throm­bocytopenic purpura occurs mostly in young females.

The aetiology and pathogenesis of the disease are unknown. It has only been established that the immune-allergic mechanism is positively involved in about 50 per cent cases: anti-thrombocytic antibodies are produced and fixed on the surface of thrombocytes to damage them and to prevent their normal separation from megakaryocytes. The triggering factors (the im­petus to production of auto-antibodies) may be infection, toxicosis, individual hypersensitivity to certain foods and medicines. In some cases the disease is caused by hereditary insufficiency of certain enzyme thrombocyte systems which is probably activated by some additional factors.

Pathological anatomy. Multiple haemorrhages in the skin and the internal organs are characteristic. The spleen may be considerably enlarged. Separation of thrombocytes from megakaryocytes in the bone marrow is disordered (according to histological findings).

Clinical picture. The main symptom of the disease is the appearance on the skin and mucosa of multiple haemorrhages in the form of small dots (petechiae) or large spots (ecchymoses). Haemorrhage may be spontaneous and due to insignificant injuries, mild contusion, pressure on the skin, etc. Haemorrhagic lesions are first purple, then they darken to cherry-red and brown, and then lighten to yellow and disappear in several days. But new lesions develop to succeed the disappearing ones. Bleeding from the nose, gastro-intestinal tract, kidneys or uterus are not infrequent; haemorrhages into the internal organs (brain, fundus oculi, myocardium, etc.) are also possible. Grave and prolonged bleedings arise in extraction of teeth or in other minor operations. The tourniquet test (and especially the pinch test) are positive. The spleen and the lymph nodes are usually not enlarged; tapping on the bones is painless.

Thrombocyte counts are usually less than 50 x 10⁹ per 1 1; in some cases only single blood platelets can be found in preparations. The degree  of bleeding can be assessed by the degree of thrombocytopenia. Hypochromic anaemia can develop after profuse bleeding. The clotting time is normal in most cases, but it can be slightly longer (due to the deficit of thromboplastic factor III of blood platelets). The bleeding time increases to 15-20 min and more; clot retraction is disordered. Throm-boelastography reveals greatly increased reaction and clotting time.

 

 

Hematomas

 

Course. Both acute and chronic recurrent forms of the disease are observed. The patient dies of profuse bleeding and haemorrhages into the vital organs.

Treatment. Removal of the spleen is indicated in grave ca^es: the number of thrombocytes increases in the blood of a patient and haemor­rhage stops in a few days following the operation. The effect of splenec­tomy is probably explained by decreased decomposition of blood platelets in the spleen and by the removal of the inhibiting effect that the spleen has on thrombocytopoiesis. Blood transfusion is useful for haemostasis and blood substitution. Repeated transfusion of thrombocytic mass gives positive haemostatic effect. Vitamin P, vitamin C, calcium chloride and vicasol are given to strengthen the vascular walls. Since the allergic factor is involved in the pathogenesis of the disease, corticosteroid hormones are quite effective in certain cases.

 

Haemophilic arthropathy of knee joint

(ІІІ-ІУstage)

 

 

 

Ankilosis of knee joint in haemophylia

 

 

 

Femoral joints arthropathy in hemophilia

 

 

ENDOCRINE DISORDERS

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 hor-mon&Tjy 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 also a very important factor which accounts for many symptoms of the disease. The role of the pituitary gland in the pathogenesis of thyrotox­icosis 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 lite 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 litlle 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 ate 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 mofst 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 paJpatirjnj)£yi£.fhy_ix»id.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  the cornea which appears as the eyeball moves downward.

 

 

 

 

 

 

 

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 mur mur 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 (lachysystolic form) due tc tlve toxic effect of the thyroid hormones on the myocardium. Circulatory in­sufficiency can also develop. Electrocardiograhic studies reveal a slighlly 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 function of the intestine accounts for diarrhoea. Hepatic dysfunction can have various effects: from slight disorders (that can only be revealed by functional lests) to cirrhosis.

Nervous system. The clinical symptoms of disorders in the higher nervous activity ate 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 “I 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 thyrotoxicosis and is divided into three degrees: 1 degree thyrotoxicosis is characterized by the absense of complications; not marked, tachycardia is moderate (to 100 beats per mm), 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 niin, 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 mint, 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.

Treatmeat. The patient should be given calm and rest; sleep should be normalized. The diet must be adequate, rich in proteins and vitamins. An­tithyroid preparations should be given: iodine, Ihiouracyl, 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.

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 hypoplasia or aplasia of the thyroid gland, iodine deficiency in the body, subtotal thyroidectomy, overdosage of ^l31,I (which is given in hyperthyroidism) or preparations ofthiourac.il 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 if 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 tare; it falls off from the brows. Movements are slow and speed] is monotonous.

Centptd and peripheral nervous systems. The mentioned complaints ate associated with changes in the function of the central nervous system. Psychosis may develop in longstanding hypothyroidism. Disorders in the peripheral nervous system are manifested by strong severe radicular pain in the extremities, paraeslhesia, cramps, and shaky gait.

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

Gaslro-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.

гормонів.

 

Congenital hypothyreosis

 

 

 

 

 

 

 

 

Appearance of patients in hypothyreosis

 

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 thyrfjid 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 metabblism 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 neutjal 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.

Risk factors in 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.

Glomerulosclerosis in diabetes mellitus

 

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

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

 

Cardiovascular system. Atherosclerosis of various arteries with the cor-isponding clinical symptoms, angina pectoris, gangrene of the feet, etc. is ot infrequent.

 

Necrosis of tissues in diabetic angiopathy

 

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

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

Kidney diseases. Arteriolosclerosis of the kidneys and intracapillary ;lomerulosclerosis (Kimmelstiel-Wilson syndrome) may occur. They are nanifested by hypertension, retinopathy, and albuminuria. Pyelonephritis s not infrequent.

Retinopathy. Retinopathy in diabetes mellitus is manifested by the jresence of exudate in the retina, haemorrhages, and pigment abnormality n 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) contains4.4~6.6 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 cuiw 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,  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 parent 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 phase3f 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 over­dosage. 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.

Anaphylactic Shock

Anaphylactic shock is a symptom complex of acute grave gen< allergic reactions of immediate type, characterized mainly by the ini stimulation and subsequent inhibition of the function of the central r vous system, bronchospasm, and a marked arterial hypotension.

Aetiology. An anaphylactic shock may be caused by repeated intakt substances which sensitize the body when taken for the first time. Usui these are medicinal preparations such as penicillin, streptomycin, procai vitamin B,, some other antibiotics, sulpha drugs, vaccines, sera, extract! pollen of some plants, etc. It is important to note that an anaphyla shock may develop after administration of small doses of the preparat which was given earlier in larger doses, e.g. in intracutaneous injectior only a few units of penicillin (in diagnostic test for allergy). An anaphy tic shock may develop from using a syringe which was sterilized toget with syringes and needles that were used to inject penicillin to other tients. Inquiry of patients predisposed to anaphylactic shock can o( reveal allergic reactions in the past history. An anaphylactic shock usu es in parenteral administration of medicines but it can also develop m these substances contact the mucosa. In some cases, an anaphylactic zk may occur from insect bites.

Pathogenesis. The pathogenesis of anaphylactic shock consists in sen­sation of the body during the first intake of the antigen (medicinal stance, vaccine, etc.) and production of antibodies, which are partly d on various tissue cells. On repeated intake of the same substance, a :tion occurs by which an antigen-antibody complex is produced, logically potent substances, such as histamine, bradykinin, serotonin, , are released immediately from the cells into the blood in large quan-s. These substances produce various effects on the organs and systems he body to cause spasms of smooth muscles and to increase vascular neability, while combination of the antigen with the circulating an-•dies activates the complement and causes formation of anaphylatoxin. itopy (hereditary allergy characterized by congenital presence of an-idies to certain allergens), an anaphylactic shock may develop during first contact with this substance.

Clinical picture. In addition to the described general symptoms, phylactic shock may have some specific /eatures. Anaphylactic shock elops rapidly, in a few seconds or minutes (to 30 minutes), following the ke of the allergen. The first symptoms are usually vertigo, headache, •, cold sweat, dyspnoea, anxiety, pressure in the chest, and paroxysm of gh. In some cases, skin itching develops simultaneously. Some patients elop allergic urticaria, allergic oedema, tachycardia, abdominal pain, liting, diarrhoea, and often convulsions. The further picture varies: dly developing oedema of the throat and asphyxia, progressive otony, oedema and haemorrhages into the internal organs (which are jcially dangerous if they affect the brain). In grave cases, the patient n loses consciousness; this is an unfavourable prognostic sign. Despite the varied clinical picture of anaphylactic shock, its diagnosis is difficult: the main sign is the rapid response of the patient to the ad-istration of the medicine. The shock may occur immediately. A routine emic examination of the patient is impossible and urgent measures nld be taken to recover the patient from the shock. This done, the sician may proceed with verification of the diagnosis.

Prognosis. The prognosis is serious in all cases: the patient may die tin the first minutes or hours of asphyxia, cardiovascular insufficiency, rreversible affections of the vitally important organs. The latter may :lop and become the cause of death at later terms (in several days). ;r the patient has been drawn from the critical state, he should be given lorough medical observation and examination by laboratory and instrumental methods (as indicated). This enables the physician to diagnose the affection of this or that organ at the early stage of the process.

Treatment. It is necessary to stop the allergic effect, e.g. to apply a tourniquet to the extremity into which the medicine was injected or which was bitten by an insect. This should be followed by administration of adrenaline (as a vasoconstrictive agent) to arrest the allergen supply from the tissues into the blood. Antihistamine preparations (dimedrol, suprastin, etc.), glucocorticosteroids and their analogues (prednisolone, etc.), having pronounced anti-allergic and anti-inflammatory action, should also be given. Depending on the special character of each particular case, symptomatic treatment should be given: oxygen therapy, cardiac glycosides, angiotonics, etc.

Prophylaxis. A thoroughly collected allergic anamnesis is very impor­tant. The patient should be asked to what preparations he might have allergic response, or if he has atopy or hereditary predisposition to allergic reactions. If this information is available, the physician should exclude those preparations to which the patient has the allergic reaction. Any room, where patients are given injections of medicinal preparations, should be equipped with all necessary means to recover patients from possible anaphylactic shock.

Allergic Oedema

Allergic oedema (angioneurotic oedema, Quincke’s oedema) is characterized by attacks of transient circumscribed oedema of the skin, subcutaneous connective tissue, and mucosa.

Aetiology and pathogenesis. This is an allergic reaction to various allergens. Vascular reactions, and in the first instance increased vascular permeability, are important factors causing allergic oedema.

Clinical symptoms. The angioneurotic oedema develops acutely, a few seconds or minutes following the intake of the allergen (usually without any precursors). As a rule, oedema affects the lip, the cheek, the eye, but it can also develop in any organ (oedema of the throat, stomach, etc.). The oedema persists from a few minutes to several hours. The size of the swollen area varies, but it rarely exceeds the size of the palm. The allergic oedema may recur, not infrequently on the same organ.

Treatment. Intravenous infusions of a 10 per cent calcium gluconate solution, administration of antihistaminic preparations, glucocor­ticosteroids (prednisolone, etc.). Symptomatic therapy is also recommend­ed (e.g. in oedema of the laryngeal mucosa).

Prophylaxis. Medicines or foods which are known to cause the allergic reactions should be excluded

 

Rheumatoid Arthritis

Rheumatoid arthritis (infectious allergic polyarthritis, infectious non­specific deforming polyarthritis) is a systemic disease of the joints, first and foremost of small joints. The incidence among women is higher than in men. Young and middle-aged individuals are usually affected. The in­cidence of the disease is rather high: according to various authors, from 0.8 to 5 per cent of the population are affected by the disease.

Aetiology and pathogenesis are unknown. The onset of the disease is usually associated with the presence of chronic infectious foci (streptococ­cal infection, unknown viruses, possibly mycoplasm). The disease is regarded as an infectious and allergic and is referred to the group of larger collagen diseases. The rheumatoid factor (antibodies t(£ the Fc fragment of immunoglobulin and mainly to the class M immunoglobulin) and an­tibodies to DNA, collagen, and to the formed blood elements are regularly found in the blood of patients with rheumatoid arthritis. It is believed that the rheumatoid factor arises in response to the production of auto- –antigens, the proteins of the affected synovial membrane of the joints. The reaction between the antigen and the antibody causes a progressive affection of the joints with further development of pathologicarproteins (auto-allergens). Hereditary predisposition to the disease is also important.

Pathological anatomy. Osteosynovitis is characteristic of the initial period. Later the cartilages and periarticular tissues are involved in the process. Fibrous-sclerotic changes develop which finally result in complete or incomplete dislocation of th£,joints, development of ankylosis and marked deformation of the joints (hence another name: deforming polyar­thritis). In addition to pronounced affections of the joints, connective tissue and vessels are also affected in various organs which makes it possible to regard rheumatoid arthritis as a systemic disease.

Clinical picture. Polyarthralgia with mostly symmetrical affection of minor joints of hands and feet, limitation of movements, which is especial­ly pronounced after prolonged inactivity, and progressive deformation of the affected joints are symptoms characteristic of the disease. But all other joints can also be involved. In some cases, the disease is monoarthritis. The onset of the disease is usually subacute, but it may be acute or prolonged Pain in the joints is especially severe in the morning; it decreases at rest. After a night sleep or prolonged inactivity, the movements are especially limited, and articulation is difficult (this symptom is explained by oedema of periarticular tissues). By the night, movements of the joints become easier. The patient may also complain of general fatigue, fever, indisposi­tion, weakness, and loss of appetite.

Inspection of patients with pronounced arthritic changes re specific deformation of the joints, their subluxation and ankylosis, most typical signs of the disease are deviation of the hand in the i direction (seal’s fin deformity), flexion contracture of proximal and h distension of distal interphalangeal joints (button-hole deformity), fl< contracture of the metacarpophalangeal joint with hyperdistension i proximal and flexion in the distal joint (swan-neck deformity o finger). Inspection is supplemented by palpation of the joints to deter their tenderness, the degree of limitation of active and passive movem

 

 

 

 

Sickness of interphalangeal joints in arthritis

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Deformities of joints in rheumatoid arthritis

 

 

Changes on X-ay in rheumatoid arthritis (ostheoporosis)

The typical changes in the hand of patients with rheumatoid art are a peculiar “visiting card” of the disease. It is an important diagr sign. Changes in the other joints are difficult to differentiate from si changes occurring in arthritis of other aetiology.

Palpation reveals a greater or lesser degree of muscular atrophy (d lack of exercise, i.e. atrophy due to inactivity and due to specific mus affection). Sometimes firm rheumatoid nodules, 0.5-1.5 cm in dian usually mobile and not adherent to the surrounding tissues, ca palpated in subcutaneous connective tissue around the elbow, ove ulnar bone, Achilles tendon, and in the occipital aponeurosis.

Lymphadenopathy, spleno- and hepatomegaly are observed in jui rheumatoid polyarthritis. In 80 per cent of cases, rheumatoid arthrit curs in the form of joint affections. The arthrovisceral form of the di occurs less frequently. In this case, direct examination of the patient laboratory-instrumental methods reveal changes specific for affectio various organs (subacute or chronic myocarditis, pleuritis, diffuse fi ing alveolitis, glomerulonephritis, or amyloidosis of various organs kidneys, liver, etc., which attend rheumatoid arthritis).

 

 

4 stages of development of RA:

А – norm;

В – fibrillation of cartilage and early subchondral sclerosis;

С –thin and rupted cartilage, early ostheophytosis;

D –Cartilage disappears, зникнення хряща, ostheophytosis, cysts.

 

Laboratory studies reveal increased ESR (to 50-60 ram/h), not quently normochromic anaemia, and also positive non-sp biochemical tests showing the activity of inflammatory processes su dysproteinaemia (hypergammaglobulinaemia, increased alpha glol and fibrinogen in the blood serum), and high seromucoid and C-rei protein in the blood. Detection of the rheumatoid factor in the I serum and synovial fluid is a more specific laboratory test for rheum arthritis.

X-raying of the joints reveals their specific changes: osteoporo bone epiphyses, narrowing and erosion of the joint slit, formath microcysts in the epiphyses, osteophytes growing by the articulatioi faces. Complete and incomplete dislocation, marked deformities c joints, and also complete overgrowth of certain articular slits can be r ed at later stages of the disease.

The disease is chronic and progressive. In most patients, it is terized by periodic exacerbations (provoked by infections, overcool-;.) and remission. The patient can die of a concurrent amyloidosis, on of the vitally important organs (heart or renal failure), and also cations associated with prolonged (sometimes, uncontrolled) ad-ration of strong medicinal preparations. These complications may be ation of steroid ulcer of the stomach, or hypertonic and diabetic ications   in   prolonged   use   of   glycocorticosteroids   and   their mes.

Treatment. Therapy includes: (1) sanation of chronic infection foci us teeth, tonsillitis,  sinusitis, etc.); (2) using non-steroid anti-lmatory analgesics (acetylsalicylic acid, butadione, bruphen, and the (3) using chloroquine derivatives (delagil, plaquenil); (4) using :orticosteroids. and their analogues) (prednisolone and the like) in cases; this should also be supplemented by local therapy (given into >int cavity); (5) remedial exercises and physiotherapy (mainly ther-srapy); (6) in individual cases, surgical treatment (synovectomy).

Prophylaxis. Prophylactic measures are not well developed. But it has shown that timely diagnosis and sanation of chronic infection foci tion of the mouth, tonsils, ears, etc.) are very important.

 

Osteoarthrosis

Osteoarthrosis (deforming arthrosis) is a chronic dystrophy of the s and periarticular tissues which causes deformation of the joints. The ise usually attacks aged and middle-aged women.

Aetiology and pathogenesis are not yet known. It is believed that arthrosis is associated with metabolic disorders in the cartilage due to remature ageing. General endocrine and metabolic disorders, chronic otrauma of the joints, and hereditary predisposition are also impor-. Synovitis, the reactive inflammation, is secondary to irritation of the >vial membrane by articular detritus (minute grains of necrotized car-;e). Compensatory irritation of the cartilage occurs also with formation isteophytes; subchondral osteosclerosis develops.

Pathological anatomy. Dystrophic changes in the cartilage impair its elasticity. The car-e surface becomes dry, opaque and rough. In grave cases, the cartilage may be affected by osis and ulceration, deformation of the joint surface, formation of osteophytes, :hondral osteosclerosis, and finally secondary arthroses. Inflammation in the cartilage periarticular tissues is usually mildly pronounced.

Clinical picture. The patient complains of pain during exercise (walk-, stepping on the affected leg) in the spinal column, the large joints of the lower extremities, and in distal interphalangeal joints of the hands. The pain is abated at rest.

Deformation of the joints and swelling around them can only be reveal­ed in grave forms of the disease. Palpation can reveal mild tenderness of tissues surrounding the affected joint. Movements of the joints are difficult only at the last stage of the disease. It concerns mostly the hip joint (coxarthrosis): patients develop waddling gait due to difficult articulation of the bones. As the disease progresses, walking becomes impossible because of dislocation or marked deformation of the hip joint. Laboratory studies do not reveal any significant changes, except a mildly increased ESR. X-rays reveal narrowing of the joint slit, the presence of osteophytes, subcar-tilaginous osteosclerosis in combination with cyst-like areas of diminished density in the epiphyses, deformities of the joints of various degrees, and in some cases dislocation of the joint.

 

 

 

 

 

Deformations of joints in ОА

 

 

Course. The disease is chronic and gradually progressive. Dislocation of the damaged joint is the possible complication.

Treatment. Therapy includes prescription of (1) analgesic and anti­inflammatory preparations; (2) intra-articular injection of trasylol (in­hibitor of the proteases that are involved in the degenerative changes in the cartilage) and arteparon (to inhibit splitting of cartilage mucopolysac charides); (3) remedial exercises and physiotherapy (mainly ther-motherapy).

 

Haemorrhagic Vasculitis

Haemorrhagic vasculitis is an immuno-allergic disease characterized by affection of the capillaries, minor blood vessels, with subsequent multiple haemorrhages. The disease was first described by Schoenlein in 1832 and then by Henoch in 1868.

Aetiology. Aetiology of the disease is uncertain, but it has been long noticed that haemorrhagic vasculitis often attends certain infectious diseases (influenza, tonsillitis, tuberculosis, etc.) or develops in the presence of hypersensitivity to some foods and medicines. Specific antibodies to endothelial cells of the vascular wall are found in the blood of patients with haemorrhagic vasculitis.

Pathological anatomy. There are multiple haemorrhages in the skin, the wall of the gastro­intestinal tract, and less frequently, in other organs. Histological studies of tissues in the zone of haemorrhage reveal affections of the capillaries and minor vessels, necrosis of their vascular wall, thrombosis, proliferation of the intima with narrowed lumen of the vessel, and focal perivascular infiltration.

Clinical picture. The disease is characterized by a sudden multiple haemorrhages in the skin, often at symmetrical points of the right and left part of the trunk and the extremities. The joints may be affected: this is attended by pain, limited movements, and swelling of the periarticular tissues. In the abdominal form of vasculitis, haemorrhagic lesions appear on the gastro-intestinal and peritoneal mucosa; the patient complains of severe pain in the abdomen, which is attended by bloody vomiting and stools; the belly is tensed, the general condition grave, like in the acute ab­domen syndrome. In certain cases, haemorrhagic vasculitis can proceed with affections of the kidneys (subacute or chronic glomerulonephritis) and other organs.

In mild cases, there are no changes in the blood, but severe haemorrhage is attended by hypochromic anaemia. The thrombocyte and fibrinogen content of blood is normal. Blood coagulability, bleeding time and clot retraction time remaiormal. The tourniquet and pinch tests, and also the Bittorf-Tushinsky symptom are positive in most cases.

Course. The disease may be acute and continue for several days or weeks, or it may be chronic, with periodic exacerbations. The patient may die of profuse bleeding or haemorrhage into vitally important organs; necrosis of the intestine and kidney affections can be other causes of death. Treatment. Treatment should be symptomatic. Calcium chloride is given intravenously to cause a weak anti-allergic effect and to strengthen the vascular wall. Salicylates and butadion are given in cases with affected joints. Corticosteroids are effective. They decrease substantially the allergic response of the body. Dimedrol, diprazine and other antihistamine preparations are also efficacious