Inquiry and general inspection of patients with diseases of urinary system

Inquiry and general inspection of patients with diseases of urinary system. Palpation of kidneys.

Examination od patients with kidney diseases

Inquiry and general inspection of patients with diseases of  the blood system. Percussion of bones. Palpation of a spleen and lymph nodes

 

Normal sizes of kidneys in men (а) and women (б).

 

Complaints. Patients with diseases of the kidneys most commonly complain  of pain in lumbar region,  disordered  urination,  oedema, headache, and dizziness. They may also complain of deranged vision, pain in the heart, dyspnoea, absencei f apjjetite, nausea, vomiting, and elevated body temperature. But diseases of the kindeys may also proceed without any symptoms of renal or general clinical insufficiency.    

If the patient complains of pain, its location should first of all be determined. Pain of renal origin often localizes in the lumbar region. If the ureters are affected, the pain is felt by their course. If the bladder is involved, pain is suprapubical. Radiation of pain into the perineal region is characteristic of an attack of nephrolithiasis.   

 The character of pain should then be determined. It is necessary to   remember that the renal tissue is devoid of pain receptors. The pain is felt  when the capsule or the pelvis is distended . Dull and boring pain in the lumbar region occurs in acute glomerulonephritis, abscess of the perirenal cellular tissue, in heart decompensation (“congestive kidney”) in chronic pyelonephritis   (usually   unilateral)   and   less   frequently  in chronic glomerulonephritis. Pain arises due to distension of the renal capsule because of the inflammatory or congestive swelling of the renal tissue.             2. Sharp and suddenly developing pain on one side of the loin can be due to the renal infarction. The pain persists for several hours or days and then subsides gradually. The pain is rather severe in acute pyelonephritis: inflammatory oedema of the ureter interferes with the normal urine outflow from the pelvis and thus causes its distension. The pain is usually perma­nent. Some patients complain of attacks of severe piercing pain in the lumbar region or by the course of the ureter 3 The pain increases periodically and then subsides, i.e. has the character of renal colic. Obstruction of the ureter by a calculus or its bending (movable kidney) is the most common cause of this pain, which is usually attended by spasmodic contraction of the ureter, retention of the urine in the pelvis, and hence its distension. The spasmodic contractions and distension of the pelvis account for the pain. Pain in renal colic is usually unilateral. It radiates into the corresponding hypochondrium and most frequently by the course of the ureter to the bladder, and to the urethra. This radiation of pain is explained by the presence of nerve fibres (carrying the impulses from kidneys, ureters, se organs and the corresponding skin zones) in the immediate vicinity of the relevant segments of the spinal cord (D_X-D_XI1 and L,-L_u). This facilitate propagation of the excitation. Patients with renal colic (like those with co ic of other aetiology) are estless; they toss in bed. Patients with severe pain of other aetiology would usually lie quiet in their beds (movements may ii tensify the pain).

The conditions promoting pain should be established. For example pain in nephrolithiasis can be provoked by taking much liquid, jolting nution, or the like; pain is provoked by urination in cystitis. Difficult an painful urination is observed in stranguria. Patients with urethritis feel burning pain in the urethra during or after urination.

It is necessary also to establish the agent that lessens or removes the pain. For example, atropine sulphate, hot water-bottle or warm bath he in renal colic. Since these remedies only help in spasmodic pain by removing spasm of the smooth muscles, their efficacy in renal colic confirms tl leading role of the ureter contraction in the pathogenesis of this pain. Pain of the renal colic-type in patients with movable kidney may lessen with changing posture: urine outflow improves with displacement of the kidney “” Pain slightly lessens in patients with acute paranephritis if a bag with ice placed on the lumbar region and if the patient is given amidopyrine or other analgesics.

Many renal diseases are attended by deranged urination: changes in the daily volume of excreted urine and in the circadian rhythm of urina

Secretion of urine during a certain period of time is called diuresis. Diuresis can be positive (the amount of urine excreted exceeds the volume of liquid taken) or negative (the reverse ratio). Negative diuresis is observed in cases of liquid retention in the body or its excess excretion through the skin, by the lungs (e.g. in dry and hot weather). Positive diuresis occurs resolution of oedema, after administration of diuretics, and in some other cases. Deranged excretion of urine is called dysuria.

Increased amount of excreted urine (over 2 1 a day) is called polyuria. can be of renal and extrarenal aetiology. Polyuria is observed in persons who take much liquid, during resolution of oedema (cardiac or renal), and after taking diuretics. Long-standing polyuria with a high relative density of urine is characteristic of diabetes mellitus. In this case polyuria arises due to a deranged resorption of water in renal tubules because of increased osmotic pressure of the urine rich in glucose. Polyuria occurs in diabet incipidus because of insufficient supply of antidiuretic hormone secret into blood by the posterior pituitary. Polyuria also occurs in the absence sensitivity of the tubules to the ADH, in affected interstice of the renal medulla of various nature, in hypokaliaemia, and hypo- and hyper-  caemia.

       Persistent polyuria with low specific gravity of  urine (hyposthenuria) is usually a symptom of a severe renal disease, e.g. chronic nephritis, chronic pyelonephritis, renal arteriolosclerosis, etc. Polyuria in such cases indicates the presence of a neglected disease with renal insufficiency and decreased absorption in renal tubules.

Decreased amount of excreted urine (less than 500 ml a day) is called iguria. It can be not connected directly with renal affections (extrarenal iguria). For example, it can be due to limited intake of liquid, during staying in a hot and dry room, in excessive sweating, intense vomiting, profuse diarrhoea, and during decompensation in cardiac patients. But in certain cases oliguria is the result of diseases of the kidneys and the urinary acts (renal oliguria), such as acute nephritis, acute dystrophy of the kidneys in poisoning with corrosive sublimate, etc.

A complete absence of urine secretion and excretion is called anuria. .Anuria persisting for several days threatens with possible development of uraemia and fatal outcome. Anuria may be caused by the deranged secretion of urine by the kidneys (secretory anuria) which occurs in severe form f acute nephritis, nephronecrosis (poisoning with sublimate or other nephrotoxic substances), transfusion of incompatible blood, and also some  general diseases and conditions such as severe heart failure, shock, or profuse blood loss.

In certain cases the secretion of urine is normal but its excretion is obstructed mechanically (obstruction of the ureters or the urethra by a calculus, inflammatory oedema of the mucosa, proliferation of a malignant tumour). This is called excretory anuria. It is usually attended by strong pain in the loin and the of the renal pelves end the ureters. Exctretory anuria is often attended by renal colic.

Renal (secretory) anuria can be of reflex origin, e.g. in severe pain (contusion, fractures of the extremities, etc). Anuria should be differentiated from ischuria, when the urine is retained in the bladder and the patient is unable to evacuate it. This occurs in compression or other affection of the spinal cord, and in loss of consciousness.

Pollakiuria (frequent micturition) is observed in certain cases. A healthy person urinates from 4 to 7 times a day. The amount of excreted urine during one micturition is from 200 to 300 ml (1000-2000 ml a day). But frequency of micturition may vary within wider range under certain conditions: it may decrease in limited intake of liquid, after eating much salted food, in excessive sweating, in fever, and the like, or the frequency may increase (polyuria) if the person takes much liquid, in getting cold, and the like circumstances. Frequent desire to urinate with excretion of meagre quantity of urine is the sign of cystitis. A healthy person urinates 4-7 times during the day time; a desire to urinate during night sleep does not arise more than once. In the presence of pollakiuria the patient feels the desire to urinate during both day any night. In the presence of chronic renal insufficiency and if the kidneys arc unable to control the amount and concentration of excreted urine in accordance with the amount of liquid taken, physical exertion, the ambient temperature, or other factors impor­tant for the liquid balance in-the body, the patient urinates at about equal intervals with evacuation of about equal portions of urine. This condition is called isuria.

Under certain pathological conditions, the frequency of urination is normal during the day time but increases during night. The amount of urine excreted during night often exceeds the amount of daily urine (nycturia). Nocturnal enuresis (nycturia) and oliguria during day time occur in cardiac decompensation and are explained by a better renal function at night, i.e at rest (cardiac nycturia). Nycturia may concur with polyuria in renal dysfunction, at the final stage of chronic glomerulonephritis, chronic pyelitis, vascular nephrosclerosis, and other chronic renal diseases (rerial nycturia). In the presence of isuria and nycturia of renal origin, which arise due to the loss by the kidneys of their concentrating ability, the specific gravity of the urine is monotonous. The condition is known as isosthenuria. The specific gravity of urine is usually decreased (hyposthenuria). The specific gravity of urine varies from 1.009 to 1.011, i.e. approaches the specific gravity of primary urine (plasma ultrafiltrate) in patients with pronounced nephrosclerosis, which is the final stage of many chronic renal diseases.

Some diseases of the bladder and the urethra are attended by difficult and painful urination. The patient would complain of change in the colour of the urine, its cloudiness, and traces of blood.

Oedema is observed in acute and chronic diffuse glomerulonephritis, nephrotic syndrome, amyloidosis’, and acute renal excretory dysfunction (anuria). It is important to ask the patient about the site that was the first to be attacked by oedema, the sequence of oedema spreading, and the rate of intensification of this phenomenon (see “Renal Oedema”).

Headache, dizziness, and heart pain may result from kidney affec­tions. These symptoms occur in those renal diseases which are attended by considerable increase in the arterial pressure, e.g. in acute and chronic glomerulonephritis or vascular nephrosclerosis. A pronounced and persis­tent increase in the arterial pressure can be among the causes of deranged vision (neuroretinitis).

Patients with diseases of the kidneys can complain of weakness, in­disposition, impaired memory and work capacity and deranged sleep. Vision may be deranged along with skin itching and unpleasant breath. Dyspeptic disorders sometimes join in: loss of appetite, dryness and unpleasant taste in the mouth, nausea, vomiting, and diarrhoea. All these phenomena are associated with retention in the body  decomposi­tion products due to renal insufficiency (see “Renal Insufficiency”) which develops at the final stage of many chronic renal diseases, and sometimes in acute diseases attended by retention of urine during several days.

Fever is the common symptom of infectious inflammatory affections of the kidneys, the urinary ducts and perirenal cellular tissue.

History of the present disease. When questioning the patient, it is necessary to establish the connection of the present “disease with previous infections (tonsillitis, scarlet fever, otitis, acute respiratory diseases). This sequence is especially characteristic of  acute glomerulonephritis. But it is sometimes difficult to establish the time of onset of the disease because some chronic affections of the kidneys and the urinary ducts can for a long time be latent. Moreover, when questioning the patient, it is necessary to find out if he had deranged hearing or vision in his childhood that might be –suggestive of congenital renal pathology.

Special attention should be given to the presence in the patient’s past history of diseases of the kidneys-and the urinary duels.(acute nephritis, pyelitis, cystitis) or symptoms that might suggest them (dysuria, haematuria, oedema, arterial hypertension, attacks of pain in the abdomen or loin resembling renal colics), since these symptoms can be connected with the present renal pathology. In certain cases the cause and the time of onset of grave kidney affections (necronephrosis) can be established by revealing industrial or domestic poisoning, intentional (or by mistake) tak­ing of some poisons (corrosive sublimate, preparations of bismuth, phosphorus, silver, large doses of sulpha preparations, or of some an­tibiotics, e.g. aminoglycosides, expired tetracyclines, phosphorus com­pounds), transfusion of incompatible blood, etc. Amidopyrin, phenacetin, barbiturates, camphor, and some other medicines can cause allergic changes in the kidneys.

The patient must be asked about the character of the disease course: it may be gradual (arteriolosclerosis, chronic diffuse glomerulonephritis, amyloidosis of the kidneys), or with periodical exacerbations (chronic pyelonephritis, chronic diffuse glomerulonephritis). It is necessary to establish the cause of exacerbations, their frequency, clinical signs, the character of therapy given and its efficacy, the causes inducing the patient to seek medical help.

Anamnesis. Special attention should be given to the factors that might provoke the present disease or have effect on its further course. For exam­ple, a common  factor promoting development of acute and chronic nephritis and pyelonephritis is chilling and cooling (poor housing or woking conditions, drafts, work in the open, acute cooling of the body before the disease). Spreading of genital infection onto the urinary system can the cause of pyelonephritis. It is necessary to establish the presence absence in the past of tuberculosis of the lungs or other organs. This helps establish the tuberculous nature of the present disease of the kidneys.

It is necessary to establish if the patient has some other diseases the might cause affections of the kidneys (collagenosis, diabetes mellitus, certain diseases of the blood, etc.). Various chronic purulent diseases (osteomyelitis, bronchiectasis) can be the cause of amyloidosis of kidneys. Occupations associated with walking, riding, weight lifting, ets., can have their effect on the course of nephrolithiasis and provoke attacks renal colic. Some abnormalities of the kidneys, nephrolithia amyloidosis, etc., can be inherited. It is also necessary to record thoroug the information on past operations on the kidneys or the urinary duct.

When examining women, it is important to remember that pregnancy can aggravate some chronic diseases of the kidneys and be the cause of so-called nephropathy of pregnancy (toxaemia of late pregnancy).

 

Physical Examination

INSPECTION

Inspection of the patient should give the physician the idea of the gravity of the patient’s condition. Very grave condition with loss of consciousness may be due to severe affections of the kidneys attended by renal ,   insufficiency and uraemic coma; the condition may be satisfactory or of moderate gravity (in milder cases). It is necessary to pay attention to the patient’s posture in bed: active (at initial stages of many diseases of kidneys), passive (in uraemic coma), or forced (in paranephritis; the tient may lie on his side with the leg flexed, bringing the knee to the domen on the affected sider. In the presence of renal colic the patien restless, tosses in bed, groans or even cries from pain. Convulsions observed  in  the   presence  of  uraemic   coma,   renal   eclampsia,   t nephropathy of pregnancy (toxaemia of late pregnancy with involvement of the kidneys).

Oedema is characteristic of acute and chronic glomerulonephrii nephrotic syndrome, and amyloidosis of the kidneys. The appearance the patient with oedema of the renal origin is quite specific. 1 face is pallid, swollen, with oedematous eyelids and narrowed eye-s (facies nephritica). In patients with more pronounced signs of pathology oedema affects the upper and lower extremities and the trunk (anasarca)

 

 

 

Patient with renal oedema.

The colour of the patient’s skin is also important. Oedematous skin in cronic nephritis is pallid due to the spasm of skin arterioles, and anaemia which attends this disease. The skin is wax-pallid in amyloidosis and lipoid ephrosis. It should be remembered that in cardiac oedema (as distinct from renal oedema) the skin is more or less cyanotic.

When inspecting a patient with chronic nephritis, it is possible to observe scratches on the skin and coated dry tongue; an unpleasant odour if ammonia can be felt from the mouth and skin of the patient (factor uremicus).   All   these   signs   characterize   chronic   renal   insufficiency uraemia).

Inspection of the abdomen and the loin does not usually reveal any noticeable changes. But in the presence of paranephritis, it is possible to notice swelling on the affected side of the loin. In rare cases, an especially large tumour of the kidney may be manifested by protrusion of the abdominal wall. Distended bladder can be protruded over the pubic bone in thin persons. The distension can be due to overfilling of the bladder, for example, due to retention of urine in adenoma or cancer of the prostate.

 

PALPATION

The posterior location of the kidneys, and also the absence of anterior approach to them due to the interference of the costal arch, makes palpa­tion of the kidneys difficult. Relaxation of the pleum and pronounced

 

 

Palpation of the right kidney of the lying patient

 

Palpation of kidney in recumbent and vertical position of a patient

 

Video_Palpation_kidney

 

cachexia can be attended by certain ptosis of the kidneys and make them ‘ accessible to palpation even in healthy subjects. But the results of palpation can only be reliable in considerable enlargement of the kidneys (at least 1.5-2 times, e.g. due to formation of a cyst or a tumour), or their displace­ment by a tumour, or in cases with a floating kidney. Bilateral enlargement of the kidneys is observed in polycystosis.

It is necessary to remember that the kidneys can move about in the range of 2-3 cm in the proximal and distal directions when the subject changes his position from horizontal to vertical, and also during respiratory movements of the diaphragm. Passive movements of the kidneys transmitted from the diaphragm during inspiration and expiration should be taken into consideration during palpation: the Obraztsov-Strazhesko palpation method should be used. The patient should be palpated in the lying or standing position. When the patient is in the horizontal position, his kidneys acre better palpated because the strain of the prelum is absent. But the movable kidney can be palpated in the stan­ding patient because it hangs by gravity and is displaced downward by the pressure of the low diaphragm.

During palpation of the patient in the lying position, his legs should be  and the prelum is relaxed and the arms are freely placed on the chest. The physician should assume his position by the right side of the patient with his left hand under the patient’s loin, slightly below the 12th rib so that the finger tips be near the spinal column. During palpation of the left kidney, the physician’s hand should be moved further, beyond the vertebral column, to reach the left part of the lumbar region. The right hand should be placed on the ab­domen, slightly below the corresponding costal arch, perpendicularly to it and somewhat outwardly of the rectus abdominis muscles. The patient is asked to relax the abdominal muscles as much as possible and breathe deeply and regularly. The physician’s right hand should press deeper with each expiration to reach the posterior abdominal wall, while the left hand presse  urnbar region to meet the fingers of the right hand. When the examining hands are as close to each other as possible, the patient should be asked to breathe deeply by “the abdomen” without straining the prelum. The lower pole of the kidney (if it is slightly descended or enlarged) descends still further to reach the fingers of the right hand. As the physi­cian feels the passing kidney, he presses it slightly toward the posterior ab­dominal wall and makes his fingers slide over the anterior surface of the kidney bypassing its lower pole. If ptosis of the kidney is considerable, both poles and the entire anterior surface of the kidney can be palpated. The physician should assess the shape, size, surface (smooth or tuberousp tenderness, mobility, and consistency of the kidneys. Bimanual palpation of the kidney can also be done with the patient lying on his side.

In contrast to other organs, an enlarged or ptosed kidney can be Ex­amined by ballottement (Guyon’s sign): the right hand feels the kidney while the fingers of the left hand strike rapidly the lumbar region in the angle between the costal arch and the longissimus thoracic muscles: the fingers of the right hand feel vibration of the kidney. In deranged urine outflow through the ureter and in pronounced distension of the renal pelvis by the accumulated urine or pus, liquid fluctuation can be felt during palpation of the kidney.

If the physician palpates some formation where he expects to find a kidney, he must check reliably if this is actually a kidney because it is easy to mistake for the kidney an overfilled and firm part of the large intestine, tumor of perirenal cellular tissue (lipoma, fibroma), an enlarged right lobe of the liver, the gall bladder (during palpation of the right kidney), or an enlarged or displaced spleen (during palpation of the left kidney). The kidney is a bean_–shaped body with a smooth surface, slipping upwards from under the palpating fingers and returning to normal position, tossed up by ballottment and giving tympany during percussion over the kidney (by overlying intestinal loops). Protein and erythrocytes appear in the urine after palpation. But all these signs are of only relative importance. For ex­ample, if a malignant tumour develops, the kidney may lose its mobility due to proliferation of the surrounding tissues; its surface becomes ir­regular and the consistency more firm; if the tumour is large, the kidney moves apart the intestinal loops and percussion gives dullness. But the kidney caevertheless be identified by the mentioned signs by different taiting it from the neighbouring organs and other formations.

Palpation of the kidneys in the standing patient was proposec During palpation the patient stands facing the physiciap sits on a chair. The prelum muscles should be relaxed and the trunk slinghtly inclined forward.

Palpation can be used to diagnose ptosis of the kidneys. Three degrees of nephroptosis can be distinguished: the lower pole of the kidney can palpated in cases with ptosis of the first degree; the entire kidney can be palpated in the second degree; and the kidney freely moves about ii directions to pass beyond the vertebral column, to the side of the o kidney, and to sink downwards to a considerable distance, in the trirddegree ptosis.

Palpation is “also used to examine the bladder. If it contains much urine especially in persons with thin abdominal wall, the urinary bladder can palpated over the pubic jone as aplastic fluctuating formation. If  the bladder is markedly distended, its superior border reaches the umbilicus.

Tenderness in palpation of the ureter along its course and sensitive over the kidneys (sensitive to pressure exerted in the angle between the 12th rib and the longissimus thoracic muscles) is of certain diagnostic importance. The area overlying the ureter extends on the anterior abdominal wall between the superior ureter point (at the edge of the rectus abdominis muscle at the level of the umbilicus) and the inferior point (at the intersection of the bi-iliac line and the vertical line passing the pubic tubercle).

 

PERCUSSION

It is imgossible to percuss the kidneys in a healthy subject because t are covered anteriorly by the inteslmal  loops whith give tympany. Dullness can only be determined in the presence of very marked enlargement of kidneys.

A much more informative method for examination of the kidney tapping. The physician places his left hand on the patient’s loin and us his right hand (palm edgefor fingers) taps with a moderate force on right hand overlying the kidney region on the loin. If the patient feels pain, the symptom “is positive (Fasterhatsky’s symptom). This symptom torn is also positive iephrolithiasis, paranephritis, inflammation of pelvis, and also in myositis and radiculitis. This decreases the diagnostic value of Pasternatsky’s symptom.

A full urinary bladder gives a dull sound on percussion of suprapubic region. The percussion is carried out from the umbilii ownward, along the median line; the pleximeter-finger is placed parallel to the pubic bone.

 

Determining Pasternatsky’s Symptom.

 

Video_percussion_kidney

 

Instrumental and Laboratory Methods

URINALYSIS

tie study of urine is important for establishing a diagnosis of and concluding on the course of the pathology. Various pathological processes occuring in the kidneys and the urinary tracts have their effect on the properties urine. Pathological metabolites may be released into the blood in us diseases. Excreted by the kidneys, these metabolites are also found e urine and their determination is therefore important diagnostically.i samples taken after night sleep are usually studied. The analysis is with the study of its phystcal properties:

he normal daily amount of urine (daily diuresis) excreted by an adult s from 1000 to 2000 ml, the ratio of the urine evacuated during the 😮 the nocturnal diuresis being 3:1 or 4:1. The daily amount of urine n 500 ml and over 2000 ml can be considered pathological under cer-conditions.

he colour of normal urine depends on its concentration and varies i straw-yellow to the colour of amber. Concentration of urochromes, ilinoids, uroerythrin and of some other substances accounts for the ur of urine. The most marked changes in the urine colour depend on presence of greenish-brown bilirubin, large quantity of erythrocytes earance of meat wastes), reddish-brown urobilin, and medicines tylsalicylic acid and amidopyrine give pink colour to the urine, lylene blue colours it blue, and rhubard greenish-yellow). Normal urine is clear. Cloudiness may be^due to salts, cell elements, mucus, fats, and bacteria.

The smell of urine is specific and not pungent. When decomposed by bacteria in- or outside the bladder, urine smells of ammonia. In the ‘presence of ketone bodies (in grave forms of diabetes mellitus), urine smells “fruity” (the odour of decomposing apples).

The specific gravity of the urine varies from 1.001 to 1.040. It is measured by an urometer (hydrometer) with the scale reading from 1.000 to 1.050. Determination of the specific gravity of the urine is of great clinical importance because it gives information on the concentration of substances dissolved in it (urea, uric acid, salts) and characterizes the con­centrating and diluting capacity of the kidneys. It should be remembered that specific gravity depends not only on the amount of particles dissolved but mainly on their molecular weight. High-molecular substances (e.g. pro­teins) account for increased specific gravity of the urine without influenc­ing substantially the osmotic concentration of the urine. The osmotic con­centration of the urine depends mainly on the presence of electrolytes and urea. Osmotic concentration is expressed in mosm/1. The maximum osmotic concentration of urine in a healthy person is 910 mosm/1 ‘(max­imum sp. gravity, 1.025—1.028). The specific gravity of the urine may ex­ceed 1.030-1.040 in the presence of high quantity of glucose (glucosuria), because the concentration of 10 g/1 increases gravity of the urine by 0.004.

Chemical analysis of urine. Reaction of the urine. The kidneys are im­portant for maintaining acid-base equilibrium in the body. The kidneys are / capable of removing the ions_af_hyikogen and hydrocarbonate from the – blood and this is a mechanism by whicb pH_of  blood is maintained cons­tant. The concentration of the hydrogen ions is the true reaction of urine (active acidity or pH of the medium). The sum of dissociated and un-dissociated hydrogen ions is the titration (analytical) acidity. The true reac­tion of urine may vary from pH 4.5 to 8.4. The pH of urine can be deter­mined colorimetrically and electrometrically. Colorimetry includes methods employing litmus paper, bromthymol blue, and other indicators, by which the pH is determined only tentatively. More accurate determina­tion of pH is done by comparing colour intensity of test solutions with standard solutions (the Michaelis method).

Special indicator papers can also be used for sufficiently accurate determination of the pH of urine in the range from 5.0 to 9.0. The mean pH value of the urine in healthy subjects (with normal nutrition) is about 6.0. The value of pH is affected by the use of medicinal preparations (diuretics, corticosteroids). Acidity of urine can increase in diabetes mellitus, renal in­sufficiency, tuberculosis of the kidneys, acidosis, and hypokaliaemic alkalosis. Urine reacts alkaline in vomiting and chronic infections of the urinary tracts due to bacterial-ammoniacal fermentation

Determination of protein in urine. Normal Wine does not practically contain protein. The small quantity of plasma proteins (to 150 mg/day), that is present in the urine, cannot be determined by qualitative tests used in practical medicine. The appearance of protein in the urine in concentrations determinable by qualitative methods is called proteinuria. It can be of renal and extrarenal origin. Organic renal proteinuria occurs in kidney af­fections due to increased permeability of glomeruli which is underlain by vascular inflammation (or structural disorganization of the basal mem­brane. Glomerular. permeability is upset by the “molecular sieve” mechanism, i.e. low-molecular proteins are lost in the first instance. This proteinuria is called selective. As the process progresses, high-molecular proteins are also lost (non-selective proteinuria). Selectivity of proteinuria is an important diagnostic and prognostic sign.

Functional renal proteinuria is connected with the permeability of membranes in the renal filter in the presence of strong stimulation, slowing of the blood flow in the glomeruli, etc. Functional proteinurias include emotional, athletic (effort), cold, and orthostatic (a condition characterize ed by the appearance of protein in the urine when the patient is in the erect posture; hence the name). In cases with extrarenal proteinuria, proteins enter the urine from the urinary and sex ducts (admixtures of inflammatory exudate); extrarenal proteinuria does not exceed 1 g/1. Tests intended to (, reveal protein in the urine are based on its thermal or acid coagulation (the urine sample should first be filtered).

Determining Bence-Jones proteins. Bence-Jones proteins occui myeloma and Waldenstrom’s macroglobulinaemia. These are light polypeptide chains, which pass an intact renal filter because of t relatively small molecular weight, and are determined by thermal precipitation and electrophoreiic study of urine.

Determining glucose in urine. The urine of a healthy person contains very small quantity of glucose (0.03—0.15 g/1) which cannot be detected common qualitative tests. Glucose in the urine (glycosuria) can be 1 physiological and pathological. In the presence of normal renal fund glycosuria occurs only in increased concentration of sugar in the b (normal sugar content of blood is 4.6-6.6 mmol/1 or 0.8-1.2 g/1), i. the presence of hyperglycaemia. The so-called renal glucose threshold (sugar concentration in the blood) does not usually exceed 9.9 mn (1.8 g/1); higher concentration of sugar indicates glycosuria.

Physiological glycosuria can be observed in persons whose diet is rich carbohydrates (alimentary glycosuria), following emotional stress, ant ministration of some medicines (caffeine, corticosteroids). Less frequent renal glycosuria associated with disturbed resorption of glucose in the  tubules: glycosuria develops in the presence of normal amount of sugar in blood. As a primary disease, glycosuria occurs in he form of renal diabetes. Secondary renal glycosuria occurs in chronic nephritis, nephritic rome, and in glycogen-storage disease. Pathological glycosuria occurs frequently in diabetes mellitus, less frequentlyln thyrotoxicosis, in pituitary insufficiency (Itsenko-Cushing syndrome), and in liver_cirrhosis.

In order to assess correctly glycosuria (especially in patients with diabetes mellitus), it is necessary to calculate the daily loss of sugar with e. Most qualitative tests used to detect glucose in urine are based on the reducing power of glucose.        

Determining ketone (acetone) bodies. The presence of ketone bodies acetone, acetoacetic and (3-oxybutyric acid) in the urine is called .etonuria. Ketonuria is usually observed in severe diabetes mellitus but it ;an also develop due to carbohydrate deficit (in gliiveToxlcosis, longstanding gastroifnlestlfRil disorders, etc.); it may develop postoperatively. Ketone bodies in the urine occur simultaneously and their separate determination is therefore clinically impracticable. The Lange test is most commonly used for the etection of ketone bodies in the urine. The test urine sample is mixed with acetic acid and njtrqgjrusside, and then ammonia is layered: a violet ring is formed at the hn^rem£e~of the liquids if the test ispositive.

Determination of bilirubin. Normal urine is practically free from bilirubin. Increased amounts of bilirubin in the urine at which common qualitative bilirubin tests become positive (bilirubinuria) occur in hepatic and subhepatic jaundice at which the concentration of bound bilirubin (bilirubin glucuronide) in the blood increases. Most qualitative tests for bilirubin are based on its conversion into green biliverdin under the aciion of oxidizers.

Determining urobilinoids. Urobilinoids are urobilin (urobilinogens, urobilins) and stercobilin (stercobilinogens, stercobilins). Urobilin and stercobilin bodies are not deterrrrfned separately. Excretion of large Ly amounts of urobilinoids in the urine i called urobilinuria which occurs in diseases of the liver (hepatitis, cirrhosis), haemolytic anaemia, and in in­testinal diseases (ententes, etc.).

Microscopy of urine sediment. A urine specimen is stirred thoroughly and its 10 ml are transferred into a centrifugal test tube. After centrifug-ing, the supernatant is decanted while the precipitate transferred onto an object glass for microscopy,) The precipitate is first examined at small and then at large magnification to study the formed elements, cylinders, and salts.

 

Urine sediments and color of urine^ 1 – relan bleeding (1 – erythrocites, 2 – leykocites), 2 variant (1 – epithelium of vagina, 2 –  leykocites), 3 – spermatorrhoea, 4 – urine sediments in kidney tumor1 – tumor cells, 2 – epithelial cells), 5 – urine sediments in honorrhoea (honococci inside of leykocites), 6 – urine sediments in echinococcosis.

7- normal color of urine,  8- urine in diabetes incipidus (light-yellow),  9 – brown transparent in heart failure, 10 – cloudy urine like meat wastes,  11- dark-brown urine in jaundice, 12 – uraturia (yellow sediment), 13 – dark urine in liver melanoma, 14 – cloudy urine with white sediment in phosphaturia.

 

Erythrocytes (red blood cells) can be altered and unaltered. Unaltered erythrocytes contain haemoglobin and appear as greenish-yellow discs. Altered erythrocytes are free from haemoglobin and are colourless one- or two-contour rings (Plate 21). These erythrocytes occur in the urine of low specific gravity; erythrocytes shrink in the urine of specific gravity. The urine of a healthy person can have single erythrocytes.

Erythrocytes may be liberated either from the kidneys or from the) urinary  tract.   The  presence  of  erythrocytes  in  the  urine  is  called haematuria. Haematuria that can only be established by microscopy is callfed microhaematuria, while haematuria revealed by macroscopy is callecf  macrohaematuria. It is important practically to decide whether haematuria is of glomerular or nonglomerular origin. In the latter case blood is liberated into the urine from the urinary tract due to the presence of stones in the pelves, urinary bladder or ureters, and because of tuberculosis or malignant  newgrowths  of  the  urinary  bladder.   In  the  presence  of glomerular haematuria, the urine usually contains much protein. Pro-teinoerythrocytic dissociation (i.e. haematuria with insignificant pro­teinuria) usually suggests haematuria associated with pathology of the urinary tract. An intermittent character of haematuria (with strongly varytensity) is another evidence of non-glomerular haematuria.

A three-glass test is used for differential diagnosis of haematuria. The patient urinates into three vessels. If the blood originates in the urinary tract (urethra), the highest amount of blood is present in the first portion of the urine; if bleeding occurs in the urinary bladder, haematuria is t highest in the last portion. If the source of haemorrhage is located in otl parts of the urinary system, all three portions of the urine contain eq quantity of erythrocytes.

Leucocytes are found in the urine as small granular rounded cells. They swell in the urine of low specific gravity. Leucocytes in the urine of a

healthy person are usually neutrophils and their amount is insignifican 1-2 in the microscope’s vision field). Increased quantity of  leucocytes in the urine (leucocyturia) indicates inflammation in the kidneys or urinery tract (urethritis, prostatitis, cystitis, pyelonephritis). Thompson’s test used for differential diagnosis of leucocyturia. The firts portion of an early morning urine specimen is collected in the first glass, the main bulk o „urine in the second glass, and only the residue in the third glass. If previaling quantity of leucocytes is found in the first portion, it indicate presence of urethritis and prostatitis. If the main quantity of leucocytes found in the third portion, this suggests the disease of the urinary bladder. Uniform distribution of leucocytes in all portions of the urine may suggest affection of the kidneys. Cell structures are quickly destroyed in all urine; it is therefore difficult to judge about the degree of leucocytes .Eosinophils are sometimes found in the urine; they differ from ..leucocytes by ample uniform refracting granularity. The presen / eosinophils suggests an allergic character of the disease.

       The degree of leucocyturia does not always correspond to the gravity  affection in chronic pyelonephritis. In the absence of active inflammatory process, the quantity of leucocytes in the urine may remaiormal method of supravital staining is widely used now. It was proposed in 1949  by Sternheimer and Malbin. Depending on their morphological prop leucocytes are coloured either red or pale-blue by a special stain (water-alcohol mixture of 3 parts of Gentian violet and 97 pa safranine). Leucocytes that are coloured blue in the urine of low s) gravity are greater in size and contain vacuolized cytoplasm with gr that are set in Brownian movement. They are found in patient pyelonephritis. Leucocyte cells (Sternheimer-Malbin cells) can be fo the urine of patients with iso- or hyposthenuria with any location source of inflammation in the urinary tract. These cells are more ofte ed “active leucocytes”. They are determiried by adding distilled water to urine precipitate to create low osmotic pressure.

Increased number of “active leucocytes” suggest activation of inflammation in the urinary tract or exacerbation of pyelonephritis.

Microscopy can reveal cells of squamous, transitional, and epithelium. Squamous epithelium cells are round polygonal; they are large, colourless, and contain a small nucleu. They enter the urine from the external genitalia and the urethra; their diagnostic tance is low. Cells of transitional epithelium line the mucosa of the y tract; their configuration is quite varied; they are smaller than ious epithelium cells; the nucleus is rounded. The presence-of large it of transitional epithelium in the urine indicates inflammatory pro-1 the pulves or the bladder. Cells of renal (cuboidal) epithelium of :s are rounded or polyhedral; they are small (slightly larger than leucocytes) and have a large, eccentrically located nucleus; their granularity is coarse. They are often found in hyaline cylinders. The presence of renal Hum in the urine is a specific sign of acute and chronic affections of the kidneys, and also of fever, toxicosis, and infectious diseases.

 Catsts are proteinous or cell formations of tubular origin; they have Irical configurtion and variable size. Hyaline casts are pro-is formations of indistinct contour with smooth and slightly granular ;e; they are found in acute and chronic nephritis, nephrotic syn-e, and also in physiological transient albuminuria. Hyaline casts can ind in the urine of practically healthy people when the pH of the urine ises sharply along with increasing specific gravity of the urine, which racteristic of dehydration. It is believed that hyaline casts are formed coprotein secreted in the tubules; but there are no reliable data that 1 confirm this conjecture. Granular casts have distinct contours; they it  of dense granular mass formed by degraded cells of renal— ilium. Their presence indicates dystrophic processes in the tubules. ‘ easts have distinct contours and a homogeneous yellow structure, presence is characteristic of chronic diseases of the kidneys. The can   also   contain   epithelial,   erythrocytary,   haemoglobin   and cyte casts, and cylindrical formations of amorphous salts, which are ostically unimportant.

Non-organized sediment” of the urine consists of salts that precipitate stals and amorphous substances. Their character depends on the col-^ composition of the urine, its pH, and other properties. Acid urine ins uric acid (yellow rhomboid-type crystals), urates (yellowish-i amorphous salt), oxalic lime, or oxalates (colourless octahedral ils that may also occur in alkaline urine). Alkaline urine ins ammonium urate, calcium carbonate, triple phosphates, amor  phosphates, and neutral calcium phosphate (Plate 26). The sediment gnostically insignificant but pathological urine can contain crystals of le, thyrosine, and leucine. The presence of thyrosine and leucine is ially characteristic of subacute dystrophy of the liver and of ihorus poisoning. The presence of lipoids in the urine is characteristic phrotic syndrome. In a polarizing microscope, lipoids give a dualletion and appear as lustrous crosses.

 

Changes of urine sediments iorm and in some types of pathology: 1 – cellular elements (1  group  – cells of plain epitheliumfrom the lower parts of urinary ducts), 2 – cells with tails, polygonic cells of renal epithelium

2 – casts in urine sediments (1- hyaline casts with sediments of salts, leukocites erythrocites, 2-  granular cast,  3- hyaline cast with sediments of salts and detritis),  3– cast in uric sediment ( 1-granular cast, 2- blood cast, 3- wax cast, 4- epithelial cast), 4 – crystl sediments in urine: 1 –amphoric urates, 2- crystals of uric acids,  5– crystals of phyphates, 6– cristalic sediment in urine ( 1- leucin, 2- thyrosin, 3- cholesterol), 7– urine sediments in jaundice ( 1- crystals of bilirubin, 2- castsimpregnated with bile pigments, 3- renal epithelial cells),  8–  crystals of sulfa drugs in urine ( 1- streprocid, 2 – sulfosalasilum, 3- sulfothiasolum), 9– urine sediment in jaundice ( 1- cholesterol crystals, 2- casts with fat sediments).

 

Addis-Kakovsky test. The test is used for quantitative determination of the formed elements in the urinary sediment. Urine collected during ten hours is stirred thoroughly, its amount is measured and a 12-minute aliqudt (l/50th of the full volume) is placed in a graduated centrifugal test tube. ( After centrifuging for 5 minutes at 2000 rpm the supernatant is removed by a pipette, while the remaining 0.5 ml sediment is stirred and transferred in­to a cell for counting blood formed elements. Leucocytes, erythrocytes, and casts are counted separately. The quantity of cells counted in one microlitre is multiplied by 60 000 to find the quantity of the formed cells of the urine excreted during the day. The normal counts are 1 000 000 for erythrocytes, 2 000 000 for leucocytes, and 20 000 for casts.

Nechiporenko’s method is now widely used to count erythrocytes and leucocytes in 1 ml of urine. The main advantage of this method is that an average sample of urine is taken for analysis and the presence of pus from the sex organs is thus excluded. A disadvantage of the method is that it does not account for diuresis. The normal counts are 1000 erythrocytes, 4000 leucocytes, and 220 hyaline casts.

Bacterioscopic and bacteriological study of urine. Urine cultures are used to establish the infectious nature of a disease of the urinary system. Sterile glassware should be used for the purpose. Whenever necessary, the urine is studied bacterioscopically for the presence of tuberculosis mycobacteria. A smear is prepared from the the urinary sediment with Ziehl- Nielsen staining. The urine is studied bacteriologically to determine qualitative and quantitative composition of its microbial flora. In the presence of  bacteriuria, it is very important to determine its degree and microorganism sensitivity to various antibiotics.

FUNCTIONAL TESTS\FOR KIDNEYS

Assessing the renal function by specific gravity and amount of the urine excreted. In conditions of water deficit, a normal person excretes a small amount of the urine with high specific gravity; and vice versa: if excess li­quid is taken, the amount of the urine excreted increases while its specific gravity_s decreases. The kidneys thus maintain equilibrium in the bodily fluids, i.e. they maintain constancy of osmotic concentration and volumes of the fluids. If the body is dehydrated, osmotic concentration of ex­tracellular fluid increases and the amount of released antidiuretic hormone (ADH) increases to increase tubular resorption of water. If the amount of taken liquid increases, osmotic concentration of extracellular fluid decreases; this decreases secretion of ADH and water resorption to increase diuresis. In pathology, the kidneys are incapable of ensuring the required osmotic gradient in the medulla and the concentrating power of the kidneys is thus upset. The impaired power of the kidneys to resorb the osmoticafly active substances without water disturbs their diluting capacity.

Zimnitsky’s test. The main advantage of this method is that the renal function is tested without interfering with the normal life of the patient. The patient collects his urine at 3-hour intervals (8 portions during 24 hours). The volume of each portion and specific gravity of the urine are determined. The volumes of daily and night urine are compared and a con­ clusion is derived concerning daily and nocturnal diuresis. Fluctuations in specific gravity of the urine during the course of the day and its maximum value are thus determined. Normally the daily diuresis exceeds the nocturnal one; volumes of urine portions can vary from 50 to 250 ml, and their specific gravity from 1.005 to 1.028. Nocturnal diuresis (nycturia) prevails in renal insufficiency to indicate longer work of the kidneys because of their impaired functional capacity. If renal insufficiency is pronounced, decreased specific gravity becomes permanent (hyposthenuria). Combination of polyuria with low specific gravity of the urine and nycturia is a specific sign of renal dysfunction.

X-RAY EXAMINATION

 The kidneys are normally not seen on X-ray pictures, except in thin in-s (oval silhouettes can frequently be seen by sides of the spinal col-:tween the 11th thoracic and 3rd lumbar vertebrae). Stones in the and the ureters are visualized by X-rays. Best seen are stones con-calcium salts (oxalates and phosphates); stones containing uratesilly not seen. In suspected tumour, X-raying is done after placing

 

 

Emphysematous phyelonephritis (gas cysts of the right kidney)

 

Kidney stone on plain X-ray

 

 

 

Dystopia of the right kidney (excretory urogram)

 

Excretory urography is carried out in hospitals: the patient is given in­travenously a contrast substance that is readily excreted by the kidneys (25-40 ml of a 30-50 per cent solution of iodine preparation verographin, urotrast, or the like) and then a series of pictures are taken by which deter­mined are the size, position and functional capacity of the kidneys (by the readiness with which they excrete the contrast substance), the’size and con-figuration of the pgjves, position of the ureters, and the presence of con-crements (Fig. 104a and b). If the renal function is strongly upset, the con­trast substance is poorly excreted, and the procedure fails to give the wanted results. Drop-infusion urography is used for diagnosis of com­plicated cases. The patient is given 200-250 ml of a 25 per cent solution of a contrast substance by drop infusion during 10-15 minutes. The dose of the infused preparation may be increased with this method while the safety of the procedure is higher since the infusion can immediately, be discon­tinued if first signs of allergic response to the contrast substance appear. The pictures of the kidneys and the ureters obtained by this technique are much better even in decreased renal function. The silhouettes of the kidneys are especially well seen on pictures taken immediately after ad­ministering the contrast substance. Retrograde pyelography is made for special indications. Liquid contrast substance (urotrast) or gaseous substance (oxygen, air) is administered into the renal pelvis through special ureteral catheter using a cystoscope. Retrograde pyelography is carried out in cases when findings of the excretory pyelography are not reliable or not sufficiently informative to establish correct diagnosis of pelvic affection. Renal angiography (nephroangiography) is used to diagnose disordered blood supply to the kidneys due to upset circulation in the renal artery (stenosis, atherosclerotic plaque, etc.). A special contrast substance (car-diotrast, and the like) is injected into the aorta (through the femoral artery using a special tube) at the level of branching of the renal arteries.

 

Stone of the right kidney (on the left side – plain X-ray picture, on the right one – excretory urogram (stone in renal calix).

Pyeloectasia of the lest kidney (excretory urogram)

 

 

Retrograde pyelography in urolithiasis (plain X–ray on the left side – stones are absent, left-side retrograde pyelography on the right side – multiple stones in renal calyx).

 

Computer tomography (normal kidneys)

Computer tomography: tumor of the right kidney

Computer tomography: stone of the right kidney

 

 

Normal transfemoral angiogram

Normal selective left-sided renal angiogram

Selective left-sided renal angiogram (kidney polycystosis)

 

Venocavography (on the left side – norm, on the right one there is defect of filling due to tumor of the right kidney

 

                                                  CYSTOSCOPY

Cystoscopy is the inspection of the urinary bladder by a cystoscope. The procedure is used to inspect the bladder mucosa, to reveal the presence of ulcers, papilloma, tumours, stones, and also to carry out some therapeutic manipulations. Using a special thin catheter, it is possible to take urine specimens from each kidney and to study the renal function (chromocystoscopy). In chromocystoscopy, the patient is given in­travenously 5 ml of a 0.4 per cent indigo carmine solution, and then the time of the appearance of coloured urine from the orifice of the ureter is noted by observation through a cystoscope. In a healthy individual, the urine coloured by indigo carmine begins passing from the ureters in 3-5 minutes following the stain administration. The appearance of the col­oured urine from the affected kidney will be delayed, or the urine will not be discharged at all.

‘       KIDNEY BIOPSY

Transcutaneous biopsy of the kidneys is now practised at nephrological departments. A piece of the kidney tissue is taken for histological, histochemical or other examinations by a long needle provided with a syringe (for aspiration). The puncture is made on the side of the loin, ovei kidney. In order to reveal the causative agent of pyelonephritis, the obtteded sample is cultivated on a nutrient media and the microbial sensitive it antibiotics is determined. Transcutaneous nephrobiopsy is used to establish the character of the tumour, to diagnose chronic glomerulonephr amyloidosis, and in some other cases, but always only for special stric indications, because of the great danger of this procedure.

 

The place of puncture biopsy of a kidney: а – the diatance from the lower pole of kidney to the span of the column; б – the distance from the lower pole of the kidney to the spina iliaca; в – lower edge of costal arch.

Kidney biopsy

 

Echography. Echography (ultrasonography) is widely used iephrology to determine the size and position of the kidneys, the condition of the renal tissue, to reveal cysts, tumours of the parenchyma, stories in the pelves, etc.

 

Transverse and longitudinal scanograms on the right kidne iorm.

Hydronephrosis of a kidney (ultrasound examination: calicies are deformed).

Stone of the left kidney

Acute left-sided pyelonephritis

 

Chronic pyelonephritis(blood flow velocity is decreased on Doppler-ultrasound).

 

Normal renal dopplerogram (on the right) and in chronic pyelonephritis (on the left side).

 

 

 

DISEASES OF THE BLOOD

Methods of Examination

Inquiry Complaints. Some general complaints, such as weakness, fatigue, ver­tigo, exertion dyspnoea, palpitation, and loss of work capacity can be symptoms of anaemia. But the same symptoms are characteristic of leukaemia and myeloid hypoplasia (aplasia). In acute and profuse haemor­rhage (e.g. gastro-intestinal), the patient develops acute weakness, vertigo, and syncope.

Many diseases of the blood system are attended by fever. Temperature   elevates to sub febrile in haemolytic and vitamin B₁₂ deficiency anaemia, which is explained by the pyrogenic effect of the erythrocyte decomposition products. Subfebrile temperature can be observed in other types of  anaemia due  to  compensatory  intensification  of basal metabolism.

Moderate and high temperatures often occur in acute and chronic leucosis,)  especially in leukaemic forms due to intense decomposition of leucocytes, during which great quantity of pyrogenic purine bases are released. This also explains increased sweating of leukaemia patients. And finally, elevated temperature may be the result of necrotic-ulcerous processes and concurrent secondary infections, especially in acute leucosis, in the ter­minal stage of chronic leucoses, and also in myeloplastic syndrome (pan­ myelophthisis, agranulocytosis). Fever in lymphogranulomatosis is un- dulant, with gradual (in the course of 8-15 days) elevation and lowering of temperature.   The patient often complains of skin itching. Intense itching in lymphogranulomatosis can be the first symptom of the disease, which develops long before the other symptoms of the disease appear. Skin itching is also characteristic of erythraemia and chronic lympholeukaemia.

Patients with many diseases of the blood system complain of poor appetite and loss of weight. Wasting is especially pronounced (cachexia) in chronic leucoses and malignant lymphoma, e.g. in lymphogranulomatosis, lymphosarcomatosis, etc. Vitamin B₁₂ deficiency anaemia is characterized by burning sensation in the tip and edges of the tongue. Iron deficiency anaemia, especially the so-called early and late chlorosis, is characterized by perverted taste: the patient readily eats chalk, clay, earth, coal (pica chlorotica). The olfaction changes as well: the patient finds pleasure in smelling ether, petrol, and other substances with unpleasant odour.

Haemorrhagic diathesis, myeloaplastic syndrome and leucosis are at­tended by increased bleeding. Haemorrhagic eruptions on the skin and mucosa develop spontaneously or due to insignificant causes (pressure, mild contusion). Bleeding from the nose, gums, gastro-intestinal tract, lungs, kidneys, and the uterus also develop. Slightest injuries to the skin and mucosa stimulate prolonged bleeding in haemophilia and in overdosage of anticoagulants.

Diseases with intense proliferation of cells of the bone marrow and its hyperplasia (e.g. acute leucosis, chronic myeloleucosis, erythraemia) are often attended by pain in the bones, especially in flat bones. The pain can be spontaneous, but it becomes especially pronounced, when pressure is exerted on the bone or it is slightly tapped over. Acute leucosis is often at­tended by pain in the throat during swallowing because of developing necrotic and ulcerous tonsillitis.

Many diseases are manifested by severe pain in the left hypochondrium due to involvement of the spleen. The spleen is quickly enlarged and its capsule is overdistended to cause dull pain in cardiac decompensation and thrombosis of the splenic vein. Pronounced enlargement of the spleen, e.g. in chronic myeloleucosis (and in some forms of liver cirrhosis), is attended by the feeling of heaviness and distension in the left hypochondrium. Sharp pain develops in perisplenitis. It is intensified during deep breathing and coughing. But the most severe pain develops in massive infarction of the spleen, torsion of the vascular-ligamentous bundle (if the spleen is mobile) and spleen rupture. If enlargement of the spleen is significant, it may be ruptured by a slight injury.

 Considerable enlargement of the liver, e.g. due to myeloid or lymphoid /metaplasia in chronic leucosis, can be the cause of a subjective feeling of ‘heaviness and pain in the right hypochondrium. Right hypochondriac pain j   of the colic type is characteristic of haemolytic anaemia. It can also be caused by pigmented stones in the gall bladder and bile ducts that are form­ed due to pronounced hyperbilirubinaemia and hypersecretion of the bile pigment.

History of the present disease. When inquiring the patient it is necessary to obtain information concerning his general condition in the period preceding the onset of the present disease and also the conjectured causes of the disease. It is necessary to establish the time of the appearance of the symptoms, to study thoroughly the dynamics of the disease, to establish if the patient had his blood examined in the past, and the results of these studies. It is also necessary to find out if the patient was treated for the present disease and the results of this treatment.

Anamnesis. When collecting the anamnesis, it is necessary to remember that improper way of life, insufficient time spent in the open air, inadequate nutrition and vitamin deficit can be the cause of anaemia. Acute and 1 chronic industrial poisoning with mercury salts, lead, phosphorus and other noxious substances, and also exposure to radiation due to neglect of safety regulations, often become the cause of affection of the haemopoietic system.

Past medical history can be quite valuable to establish the aetiology of the present disease. Diseases of many organs that can be complicated by obvious or latent haemorrhages (e.g. tumours or ulcers of the gastro­intestinal tract, bronchiectasis, pulmonary tuberculosis, etc.) can be the cause of anaemia. Atrophy of the gastric mucosa and removal of the stomach or even its partial resection can impair assimilation of iron and vitamin B₁₂, which are prerequisites for normal erythropoiesis. Chronic diseases of the liver are often accompanied by the haemorrhagic syndrome due to upset production of some coagulating factors, e.g. prothrombin and fibrinogen. Severe anaemia may develop against the background of chronic diseases of the kidneys attended by renal insufficiency. Prolonged uncontrolled intake of medicinal preparations without doctor’s prescript tion (amidopyrin, butadione, chloramphenicol, sulpha drugs, cytostatics, etc.) can inhibit the function of the bone marrow and provoke haemolytic or aplastic anaemia and the haemorrhagic syndrome.

Some diseases of the blood system can be hereditary. These are haemolytic anaemias and haemophilia. It is therefore necessary to inquire the patient about his relatives, paying special attention to the presence in them of signs of anaemization or increased tendency to haemorrhages.

Physical Examination

INSPECTION

Inspection reveals the general condition of the patient and his con­sciousness. Many diseases of the blood system are characterized by a very graye condition and loss of consciousness at their terminal stages. Obeserve are progressive anaemia, myeloid aplasia, and leucoses.

The skin and mucosa should be inspected at diffused daylight. Their colour is important: anaemia is characterized by pallor of the skin and visi­ble mucosa, the hue differing in various types of anaemia. For example, the skin of patients with juvenile chlorosis is “alabaster” pallid, sometimes with a greenish hue. The skin of patients with vitamin B₁₂ deficiency is slightly yellowish and waxy. The yellow hue of the skin and visible mucosa are more pronounced in haemolytic anaemia. It should be remembered that a mild yellow hue can be easier revealed on the sclera. Pallid skin does not always indicate anaemia and can also be due to special anatomic pro­perties of the skin (deep vascularization), spasm of the peripheral vessels (collapse, nephritis), and some other factors. Moreover, pallor of th can also be masked by its hyperpigmentation (tan due to exposure sun). A more informative sign is therefore pallor of the m\ Anaemization can easier be revealed by inspecting the conjunctiva upper and lower eyelids. In chronic leucoses the skin becomes gr Erythraemic patients have “plethoric” cherry-red skin, the colour especially marked on the face, the neck, and the hands.

Pallor of conjunctiva in anaemia

 

Haemorrhagic spots of various size and shape (from petechia ai chymoses) develop on the skin and mucosa of patients with haemon diathesis; large haemorrhagic spots are called bruises. Haemorrhaj sions are first red but as haemoglobin converts into biliverdin, biliru its other coloured products of oxidation, the colour changes to cherry green, and yellow (before the ecchymosis resolves). In contrast to inflamatory rash and telangiectasia, haemorrhagic spots do not disappear they are pressed upon.

Trophies of the skin is also important. The skin is dry and soitk scaling in patients with iron deficiency anaemia. Hairs become brittle their ends break.

Changes characteristic of some diseases of the haemopoietic system be revealed during inspection of the mouth. Pronounced atrophy ( –tongue papillae is characteristic of vitamin B₁₂ deficiency anaemii tongue surface becomes smooth, as if varnished (Hunter’s glossitis jense caries of the teeth and inflammation of the mucosa round c necks (alveolar pyorrhoea) often occur in patients with iron defic anaemia. Nectoric ulcerous tonsillitis and stomatitis are frequent s toms of acute leucosis.

Regional swelling on the neck, above the clavicles, in the armpit the groin, less frequently swelling of other location can be revealed 1 spection of patients with certain forms of leucosis. This is explained considerable enlargement of the corresponding lymph nodes that be palpable (see below). The left part of the abdomen is distended in siderable enlargement of the spleen (e.g. in chronic myeloleucosis), v can also be confirmed by palpation.

PALPATION

Patients suspected for leucosis or some forms of anaemia should palpated to examine the bones: palpation of flat bones or epiphyses( tubular bones (and also tapping over them) is painful in the presence marked hyperplasia of the bone marrow.

Palpation of the lymph nodes and the spleen is however more informative.  Enlargement  of lymph  nodes  is  most  pronounced  in pholeucosis, lymphogranulomatosis, and lymphosarcoma. These dis   haracterized by regular and multiple affection of the lymph nodes, lymph nodes of only one group are first affected, but later other groups become involved too (both surface and deep nodes of the astinum and the abdominal cavity). It should be remembered that h nodes can be enlarged not only in diseases of the blood system but in some other diseases, such as tularaemia, tuberculosis, cancer stases, etc.

     Enlarged lymph nodes in leucoses and malignant lymphomas are ess, they never fuse with the skin, do not suppurate or form fistulae, stinct from affections of other aetiology (e.g. in tuberculosis). The s are pasty and elastic in lymphoid leucosis; in lymphogranulomatosis, especially in lymphosarcoma, they are firm and fuse into con lerates, sometimes as large as 15-20 cm in diameter, lie spleen should be palpated with the patient in the recumbent posior on his right side. In the former case the patient should lie on a low  w, the arms and the legs being stretched. If the patient lies on his right his head should be slightly down, the left elbow bent and resting freely. e chest; the right leg should be stretched and the left knee bent and m up to the chest. The prelum is relaxed to a maximum. In this posr the spleen is displaced anteriorly to facilitate its palpation even if it is totaly enlarged. The physician sits on the right side of the patient and i him. The left hand of the physician is placed on the left part of the patient’s chest, between the 7th and 10th ribs in the axillary lines and slight esses on the chest to limit its respiratory movements. The physician’s t hand is placed on the anterolateral surface of the patient’s abdominal  at the edge of the costal arch, at the point of junction of the costal    and the 10th rib, or (if preliminary inspection and percussion suggest enrged spleen) at the antero-inferior edge of the spleen. During expiration physician moves his hand gradually into the abdomen to form a   ch and the patient is asked to make a deep inspiration. If the spleen is palpable (and provided the palpation is performed correctly), it is displaced    during inspiration by the descending diaphragm to come in contact with palpating fingers of the right hand and to slip over them. This tipulation should be repeated several times in order to examine the enpalpable edge of the spleen. The size, shape, sensitivity, density,  lility, and configuration of the anterior edge of the spleen should determined by palpation.

One or several notches on the anterior edge of the spleen can be a palpated if its enlargement is considerable. The notches are used to identify  spleen (to differentiate it from other organs, e.g. from the left kidney) I i anterior surface of the enlarged spleen emerges from under the costal   i and also becomes palpable.

A normal spleen is impalpable. It can only be palpated in rare cases of extreme ptosis, and more frequently in enlargement of the organ. The spleen is enlarged in some acute and chronic infectious diseases (enteric and recurrent fever, Botkins’s disease, sepsis, malaria, etc.), in liver cirrhosis, thrombosis or compression of the splenic vein, and also in many diseases of the haemopoietic system (haemolytic anaemia, thrombocytopenic purpura, acute and chronic leucosis). A considerable enlargement of the spleen is called splenomegaly. The greatest enlargement of the spleen is observed at the terminal stage of chronic myeloleucosis: it often occupies the entire left part of the abdomen, while its lower pole is found in the small pelvis. After the size of the spleen is determined by palpation and its contours marked on the skin of the abdomen by a dermograph, a skin test is sometimes per­formed with subcutaneous injection of 1 ml of a 0.1 per cent adrenaline solution (Frey test) by which the contractile function of the spleen is deter­mined. In most cases the smooth muscles of the spleen contract in response to adrenaline to diminish 2-3 times. The spleen does not diminish ap­preciably in this test in the presence of its fibrosis, in perisplenitis, or in the presence of its tumours or cysts.

The spleen is not firm in acute infectious diseases; it is especially soft (the consistency of dough) in sepsis. In chronic infectious diseases, liver cir­rhosis, and leucosis the spleen is firm, especially in amyloidosis.

In most diseases the spleen is insensitive to palpation. It becomes tender in infarction, perisplenitis, and in distension of the capsule, due to the rapid enlargement, e.g. in venous blood congestion due to thrombosis of the splenic vein. The spleen surface is usually smooth; the edges and the surface are irregular in perisplenitis and old infarctions (depressions in the surface). In syphilitic gummas, echinococcosis, cysts and very rare tumours of the spleen its surface is tuberous.

Video_Palpation_spleen

The spleen is normally quite mobile, but the mobility becomes limited in perisplenitis. A markedly enlarged spleen remains motionless during respiration but it can however be displaced by the palpating fingers.

Not only the spleen but also the liver sometimes becomes enlarged due to metaplasia (as determined by palpation).

PERCUSSION

Percussion is not important for the study of the haemopoietic organs; it is only used to outline tentatively the spleen. Since the spleen is surrounded by hollow organs (the stomach, the intestine), which give loud tympany during percussion, it is impossible to determine accurately its borders by percussion.

During percussion, the patient stands upright or lies on his right side. Light percussion should be used with transition from clear resonance to dullness. Obraztsov’s percussion is recommended. In order to determine the transverse dimensions of the spleen dullness, percussion is carried out in the line passing 4 cm laterally of the left costoarticular line (the line con­necting the sternoclavicular articulation with the free end of the 11th rib). Normally spleen dullness is determined between the 9th and 11th ribs. It is 4-6 cm wide. The long axis of the spleen is percussed by the 10th rib; nor­mally the anterior edge of the spleen does not extend beyond the costoar­ticular line; its dullness zone is 6-8 cm long.

Video_Percussion_spleen

 

Splenomegaly in leycosis

AUSCULTATION

Auscultation is used to study the spleen: peritoneal friction sound can be heard in perisplenitis in the region overlying the spleen.

 

MORPHOLOGICAL STUDY OF THE BLOOD

Total blood counts are widely employed. Blood studies include quan­titative and qualitative determination of the composition of the formed blood elements: counting erythrocytes and determining their haemoglobin contents, total leucocytes and their separate forms, and platelets. Addi­tional counts are sometimes necessary depending on the character of the disease (counting reticulocytes, deriving the thrombocyte formula, etc.).

Determining haemoglobin. There are the following three major groups of methods for determining haemoglobin} colorimetric (widely used practical medicine), gasometric, and determination by the iron contain in the haemoglobin molecule. Sahli’s method of estimating haemoglol (1895) was widely used until recent times.

he cyanmethaemoglobin method has now been universally accepted the most accurate and objective technique, which was approved by the ternational Standardization Committee (in haematology). The methoc based on oxidation of haemoglobin (Hb) to methaemoglobin (MetHb Hi) by potassium ferricyanide. Methaemoglobin reacts with CN-ion form a stable red complex, cyanmethaemoglobin (CNMetHb) haemoglobin cyanide (HiCN). Its concentration can be measured oi spectrophotometer, photoelectrocolorimeter, or haemoglobinometer.

 According to this method, 0.02 ml of blood taken from the finge transferred into 5 ml (dilution 1:251) of a transforming solution consist ‘of acetone cyanhydrine, potassium ferrocyanide, and sodium hydrot bonate; the mixture is stirred thoroughly, allowed to stand for ten minu and the optical density of the solution is measured at 500-560 nm (a gr optical filter) against a blank solution (the transforming solution or r water). Concentration of haemoglobin is determined from a calibral /curve. Concentration of haemoglobin in healthy people varies fi 120—140 g/1 in women and from 130—160 g/1 in men.

Erythrocyte counting. In order to count erythrocytes in the chaml blood is diluted to 1:200 in 3.5 per cent sodium chloride solution. To 1 end 0.02 ml of blood is added to 4 ml of the diluting solution. The mixiture is stirred thoroughly and transferred into the counting chamber.

The counting chamber is a glass plate  with one or two counting grids. Bi haemacytometers are usually  used for the purpose. Three elevated strips, separated  from other by grooves pass across the main plate. The middle strip is divided into halves by an groove. Each  half has a graduated counting grid. The lateral strips are 0.1 mm higher lha middle one. The cover  lass rests  on the elevated lateral strips to ensure a 0.1 mm spaciri tween the grids and the cover glass (the depth  of the counting chamber). In order to ensui accurate spacing, the cover glass should be pressed tightly

Against the strips. A well-w; and wiped glass is ground-in by reciprocating sliding movements until the iridescent (N> nian) rings and lines appear over the lateral strips. A drop of diluted blood is place under the ground-in cover glass. The fluid is sucked in by capillary force to fill the river the grid, le blood was diluted in a test tube, the mixture should be first jolted, then a glass rod into the fluid and a hanging drop transferred onto the slit between the counting sr and the cover glass. Counting should be done one minute later (when the icytes precipitate to the chamber bottom).

   There exist many counting grids but they all employ one principle. They >t of larger and smaller squares with the area of 1/25 and 1/400 mm², lively. Goryaev’s grid is commonly used. It con-jf 225 greater squares, 25 of which are divided into smaller ones, 16 es in each greater square. Erythrocytes are counted in 5 greater squares (divided into smaller ones). A certain rule is followed in counting: ire counted in each square in one direction, and then this direction is sed in the next row of squares, as shown by the arrow in Fig. 108. ted are not only the cells inside the square but also those lying by two (e.g. the left and the upper line) without counting blood cells lying on _x ght and lower line. The quantity of erythrocytes counted in 5 greater es is recalculated with reference to one litre. Normal erythrocyte counts in women are 3.9—4.7 x  10¹² and in men x 10¹²per 1 I of blood..

There are instruments by which the counting procedure is either/ lified or automated. These are erythrohaemometres and absorgz. nres where concentration of erythrocytes is assessed by the amount of rbed or scattered light passed through a suspension of erythrocytes, or totally reading automatic instruments. In the latter case blood cells pass a >w capillary to change resistance of an electric circuit. Each cell gives a pulse on the screen of an oscilloscope and is recorded on the instrument scale.

 

Normal erythrocites

 

 

Hypochromic erythrocitesOnce the quantity of erythrocytes and haemoglobin in a given blood specimen is known, it is possible to calculate the haemoglobin content of each erythrocyte. There are many methods by which haemoglobin saturation can be determined. One of them is the calculation of the colour index. This is a conventional value derived from the ratio of haemoglobin to the number of erythrocytes. This value is found by dividing a tripled quantity of haemoglobin in grams by the first three figures expressing the quantity of erythrocytes. Normally this value approaches 1. If it is less than 1, the erythrocyte saturation of haemoglobin is insufficient; if the value exceeds 1, the volume of erythrocytes is higher thaormal. Oversaturation with haemoglobin is impossible. A normal erythrocyte is saturated with haemoglobin to the utmost limit.

At the present time, in accordance with the general tendency to express blood constants in absolute values, the weight percentage of haemoglobin in erythrocytes is calculated, instead of determining the colour index of the blood. To that end haemoglobin content in one litre is determined and the found quantity divided by the number of erythrocytes in the same volume. Normally one erythrocyte contains 33 ng of haemoglobin.

 

Macrocites

 

Microspherocites

 

Ovalocites

 

Immune haemolitic anaemia (erhthroblast and reticulocites)

 

Reticulocites

 

Leucocyte counting. Blood for counting leucocytes is diluted either in a special mixer or a test tube. A 3-5 per cent solution of acetic acid destroy­ing erythrocytes is mixed with a small amount of a suitable aniline dye to stain leucocyte nuclei. The counting chamber is filled as for counting erythrocytes. It is convenient to count leucocytes in 100 greater (undivided) squares. A constant factor is found from the dilution of blood and the volume of fluid in each square. With 1:20 dilution it is 50. When test tubes are used for dilution, 0.02 ml of blood is added to 0.38 ml of the diluting liquid in the test tube. Saponin is used for haemolysis of erythrocytes in automatic counting instruments. The normal leucocyte counts are 4000-9000 in 1 pi or 4.0-9.0 x 10⁹ per 1 1 of blood.

The leucocyte formula is counted in stained smears. An adequate smear tneets the following requirements: it is thin and the formed elements are ar­ranged in one layer; the smear is yellow and semitranslucent. The width of the smear is 2-3 mm narrower than the glass, while the length, 2/3-3/4 the length of the glass. A good smear is uniform and the cells are intact (not damaged during their application to the glass). In order to ensure an even layer, the glass is first  defatted over a gas burner or in a mixture of alcohol and ether. A small drop of fresh blood is touched by the glass edge and spread immediately over the entire glass surface. A polished cover glass of the counting chamber or another object glass with polished edges and made slightly narrower than the main object glass can be used for the purpose.

This glass is positioned behind the blood drop at an angle of 45° to the plane of the first glass and moved back to bring it in contact with the blood. As soon as the blood spreads over the entire width of the polished edge, the glass is moved forward along the surface of the object glass. Blood is thus spread in an even layer over the object glass. Before staining, the smear is fixed in methanol for 3 minutes, or in ethanol or a mixture of ethanol and ether for 30 minutes. Other fixing agents can also be used. When the smear is dry it is covered witha layer of stain.

Differential staining is used for blood cells. Romanovsky-Oiemsa staining method is com­monly used. The stain is a mixture of weakly acid (eosin) and weakly alkaline (azure II) stains. Depending on the reaction of the medium, the cells and their parts differently accept the stain: acid (basophilic) substances are coloured blue by azure, while alkaline (oxyphilic) substances are coloured red by eosin. Neutral substances accept both dyes and turn violet. Azure II, which is generally blue, contains a small quantity of azure I. In some cells the cytoplasm con­tains grains which selectively accept red azure I. The grains are called azurophilic.

Romanovsky-Giemsa stain is diluted before use with distilled water, 1-2 drops per 1 ml of water. Smears are placed on glass rods fixed in the sides of the cell and the stain is added in the maximum quantity that can remain on the glass. The staining time (15-30 min) depends on concentration of the stain, quality of water (neutral) ^^A temperature; it is determined em­pirically. The stain is then removed by a jet of water and the smears are placed in the vertical position to dry.

Differential blood count is the percentage of separate forms of blood leucocytes. In order to ensure accuracy, it is necessary to observe not less than 200 leucocytes using the immersion system. Since the cells are not evenly distributed over the surface (larger cells tend to move toward the edges) it is necessary to follow a certain rule in counting, so that both the centre and the peripheral parts of the smear might be inspected. The smear can be moved from its upper edge to the lower one, then in the lateral direction, through 2 or 3 fields of vision, then back, from the lower to the upper edge, and so on. According to another method, the smear is moved from the edge, through 5 or 6 vision fields toward the centre, then the smear is moved in the lateral direction through the same distance, then again to the periphery, and so on, until 50 cells are counted. Four sites by the four angles of the smear should be thus inspected. Each cell should be identified and recorded. A special 11-key counter is convenient for cell counting. When 200 cells are thus counted, the number of each leucocyte is divided by two.

Leucocytes quickly respond to various environmental factors and changes inside the body. Shifts in their counts are very important diagnostically. But individual variations in leucocyte composition are quite significant and it is therefore necessary to compare individual findings not with the average values, but with a certain range within which these varia­tions are normal.

When assessing the composition of leucocytes, it is necessary to bear mind that changes in percentage ratios can give an incorrect picture of 1 shifts occurring in the blood. For example, an increase in the absolmount of a given type of cells in the blood decreases the percentage of other cell elements. The picture is reverse with decreasing absolute amoi of this given type of blood cells. A correct conclusion can be derived 1 from relative (percentage) but absolute values, i.e. the quantity of a gr type of cells contained in 1  (in 1 1 of blood, according to the SI).

The total quantity of leucocytes alone is of great diagnoi significance,  because it characterizes the condition of the haemopoit system and its response to harmful effects. The increased number leucocytes (leucocytosis) is the result of activation of leucopoiesis. 1 decreased number of leucocytes (leucopenia) depends on the inhibition the haemopoietic organs, their exhaustion, increased decomposition leucocytes under the effect of antileucocytic antibodies, etc.

Neutrophils are the most changeable group of leucocytes. Their num increases in many infections, intoxication, and tissue decompositii Neutropoiesis is characterized not only by the increased total number neutrophils but also by the appearance in the blood of immature forms:

quantity of stab neutrophils increases; juvenile neutrophils and v myelocytes appear. This rejuvenation of the neutrophil composition is c  ed the blood shift to the left, because the figures grow on the left side of laboratory blank where leucocyte counts are normally record Regenerative and degenerative shifts are distinguished. In the regeneral shift to the left the mentioned changes are observed, while in degenerative shift to the left, the number of stab neutrophils only increa along with the degenerative changes ieutrophils in the absence leucocytosis (vacuolization of cytoplasm, nuclear pyknosis, etc.). 1 regenerative shift indicates active protective response of the body, while degenerative one indicates the absence of this response. The protective r of neutrophils consists in phagocytosis, bactericidal action, and product of proteolytic enzymes promoting resolution of necrotized tissue and healing of wounds.

The regenerative shift to the left occurs most frequently in the presence of an inflammatory or necrotic focus. An especially marked shift to the I (to promyelocytes and even myeloblasts in the presence of signific leucocytosis) is called leucaemoid reaction. The number of neutrophils decreases (absolute neutropenia) in the presence of the inhibiting action toxins of some microbes (e.g. causative agents of typhoud fever brucellosis) and viruses, ionizing radiation, and some medicinal prepations.

The absolute number of lymphocytes increases less frequently. Lj phocytosis occurs during recovery in acute infectious diseases, infectious mononucleosis, infectious lymphocytosis, lymphoid leucosis, rubella, brucellosis, and thyrotoxicosis. More frequently lymphocytosis is only relative, associated with a decreased number of neutrophils (Tike relative lymphopenia in the presence of increased number of neutrophils). Ab­solute lymphopenia occurs in radiation sickness and systemic affections of the lymphatic system: lymphogranulomatosis and lymphosarcoma.

Eosinophils are present in the blood in relatively small quantity but their number increases, and sometimes significantly, in allergic processes (serum sickness or bronchial asthma), in helminthiasis, and itching der­matosis. Eosinophilia in allergic processes is associated with the role played by eosinophils in removal of toxic substances produced in these reactions. Decreased number of eosinophils (eosinopenia), to their complete absence, occurs in sepsis, severe forms of tuberculosis, typhus, and poisoning.

Basophils are carriers of important mediators of tissue metabolism. Their number increases in sensitization of patients and decreases markedly j during decomposition caused  by the repeated  administration of the allergen.

Increased number of monocytes (monocytosis) indicates development of the immune processes. Monocytosis occurs in some chronic diseases) (e.g. chroniosepsis, tuberculosis, malaria, visceral leishmaniasis, syphilis) and in infectious mononucleosis. Monocytopenia sometimes occurs in severe septic (hypertoxic) forms of typhoid fever and other infections.    

Leucocyte counting procedure requires special skill. The laboratory technician should be able to differentiate between various blood cells. Granulocytes have specific segmented nuclei (violet like in all leucocytes) and oxyphilic (pink) cytoplasm containing grains. Grains of a neutrophilic leucocyte (10-15 \ixa) are small, their size varies; they are stained brown-violet. The nucleus has a rough structure, with alternation of intense- and light-coloured sites; it consists of 2 to 5 (mostly 3~ort) segments of various size and shape connected by thready bridges. The nucleus of a stab neutrophil is about the same size and colour, but it is a uniform curved band which never  thins to a thread. The eosinophil nuclei consist mostly of two symmetrically arranged segments of about the same size (three segments can also be present); their structure and colour are similar to those of neutrophil segments. Eosinophils are highly granular, Grains are large, round, bright-orange and of equal size; they stuff the en­tire cytoplasm. The diameter of the cell is about 15 /xm. A basophil is slightly smaller than the other granulocytes (9-14 ^m). The nucleus can be segmented. Often it has an irregular oval shape and is stained intensely. The grains are large and dark-violet; their size varies. Due to metachromasia, their dark-blue colour makes them look violet.

Agranulocytes are characterized by a non-segmented nucleus and basophilic (blue) cytoplasm.  The lymphocyte is  the smallest of all leucocytes; its diameter usually varies between 7 and 12 pm, but some lym­phocytes are as large as 12—15 fim. The nucleus is round, oval, or bean-shaped; it occupies almost the entire cell and is intensely coloured. The cytoplasm of most lymphocytes surrourfrJs the nucleus by a narrow circle; it is pale-blue and becomes lighter toward the nucleus. In addition to these “small” lymphocytes, there are “medium size” ones having a large sky-blue zone of a cytoplasm. Some lymphocytes have several large cherry-red (azurophilic) grains in their cytoplasm. A monocyte is the largest blood cell. Its, diameter is 20 /on. Its large nucleus is of irregular shape and I relatively light-coloured. The cytoplasm is greyish-blue and smoky; the colour intensity does not diminish toward the nucleus. If stained well, dustlike azurophilic granularity is revealed in some cells.

In rare cases, apart from the mentioned cells, normal blood contains plasma cells. Their number increases in pathology. The cells have an eccen­trically arranged dense nucleus (often a wheel-like structure) and a marked-1 ly basophilic vacuolized cytoplasm. Their number increases in certain in­fectious diseases, wound sepsis, hypernephroma, myeloma, etc. These cells are probably responsible for the production of gamma globulins.

When counting leucocytes, it is necessary to pay attention to both quan­titative and qualitative shifts in the formed elements. The degenerative ‘ shifts were discussed above. In grave toxicosis, granularity of neutrophils becomes even more pronounced, the granules become larger and coloured; this granulation is called toxicogenic. Indistinct spots are sometimes reveal­ed in (blood smears; they are stained like the nuclear substance of leucocytes. These are Botkin-Gumprecht shadows, the remains of nuclear chromatin characterizing brittleness of leucocytes due to which they decompose (teucocytolysis).

Erythrocytes are studied in the same smears. The size, shape,  colour and cell inclusions should be assessed. Normal erythrocytes in the j smear are rounded, their diameter varying from 6 to 8 jtm (the average j diameter, 7.2 fim). The size of erythrocytes often changes in anaemia of j various nature. Various  erythrocytes change differently. Excessive variation in the size of erythrocytes is called anisocytosis. Prevalence of smaller erythrocytes    (microcytosis)    occurs    in    iron    deficiency    anaemia. Macrocytosis   develops   in   haemopoietic   dysfunction   of   the   liver.

Erythroblast

 

Myeloblast

Lymphoblast

 

Megalocytes (large, over 12 ^m, oval hyperchromic erythrocytes formed during maturation of megaloblasts) appear in the blood of patients with vitamin B₁₂ deficiency (vitamin B_]2 deficiency anaemia). In pathological conditions of erythrocyte maturation, along with anisocytosis, the change in the shape of erythrocytes (poikllocytosis) is also observed; in addition to round erythrocytes, blood contains also erythrocytes of oval, pear-shaped and other configurations. If erythrocytes are undersaturated with haemoglobin (colour index less than 0.85) they are poorly stained to become hypochromic; in vitamin B₁₂ deficiency they are coloured intense­ly, i.e. hyperchromic (colour index higher than 1). A mature erythrocyte is oxyphilic, i.e. coloured pink. An immature erythrocyte is polychromatophilic. In supravital staining these erythrocytes appear as reticulocytes (see below). Normal blood contains polychromatophilic erythrocytes in meagre quantity: single cells per 1000 erythrocytes. Since they are less noticeable than reticulocytes, the latter are counted to assess the number of juvenile polychromatophilic cells. The importance of this count is that the number of reticulocytes in the blood is a measure of the activity of the bone marrow. Normally this number is 2-lOjper 1000 erythrocytes. Erythropoiesis is activated in blood loss and haemolysis, and the number of reticulocytes iormal bone marrow and peripheral blood increases. The absence of this increase indicate  decreased function of the bone marrow and conversely reticulocytosis ^;.i the absence of anaemia in­dicates latent but well compensated loss of blood. High Veticulocytosis is observed in effective treatment of vitamin B₁₂ deficiency anaemia.

In erythropoietic hypofunction of the bone marrow, more immature nuclear (but still containing nuclei) elements of the red blood, i.e nor­moblasts and erythroblasts, are delivered into the blood from the bone marrow. During maturation of erythrocytes in pathological conditions, nuclear remnants, known as Jolly bodies, may be preserved. These are round chromatin formations 1-2 cm in size, stained cherry-red. Red Cabot rings (thread-like rings or convolutions) may also remain. They are believed to be the remnants of  the nuclear envelopes, and occur mostly in vitamin B₁₂ deficiency anaemia.

Basophilic granulation of erythrocytes is also the result of their abnor­mal maturation. Blue granules are seen against the pink background during ordinary staining of a fixed smear. It should not be mistaken for reticulocyte granulation which is revealed only in supravital staining. Basophil-granular erythrocytes occur in pernicious anaemia and some in­toxications, especially in lead poisoning.

Reticulocytes are stained in unfixed smears of fresh blood in which erythrocytes are still alive. Various alkaline dyes are used to stain smears by various techniques. Best results are attained with brilliant cresyl blue. A drop of a saturated alcoholic solution of the stain is applied to a defatted object glass and a smear is made by the usual way. As soon as the stain dries up, a thin blood film is smeared over it and the glass is transferred to a moist chamber (a Petri dish containing a piece of wet blotting paper). The smear is kept there for 5 minutes and then removed and allowed to dry.

The smear is inspected with an immersion system. Mature erythrocytes at stained green. Against this background, reticulocytes (depending on the maturity) have blue granules, filaments, or other formations that ms resemble a crown, a ball, or a network. Filaments and grains are more mature forms and they usually predominate in reticulocytes.

When counting reticulocytes, their number per 1000 erythrocytes determined.  For  convenience  of counting,  the  vision   field  of the microscope is diminished by placing a special window in the eye-piece. The total number of erythrocytes and reticulocytes is counted in the field of  erythrocytes Counting is continued till the number of erythrocytes is 1000.

Thrombocytes (platelets) have a diameter of 1.5-2.5 /tm. Their norm number is 180.0-320.0 X 10⁹ per 1 1 (180 000-320 000 per 1 n\) of blood Using the Romanovsky-Giemsa staining technique, the central part, the granulomere with intense azurophilic granulation, and non-granul hyalomere around it are distinguished. If the number of thrombocyt decreases significantly (thrombocytopenia), a tendency to haemorrhag develops. The critical figure at which haemorrhage occurs is believed to 30 x 10⁹ per 11 (30 000 per 1 /il). Thrombocytopenia occurs in affection the bone marrow by infectious causative agents, some medicinal preparations, ionizing radiation, and in auto-immune processes. Thrombocyto: Occurs after haemorrhage, in polycythaemia, and malignant tumours. ( In order to determine the number of thrombocytes, it is necessary prevent their agglutination. To that end, a drop of a 14 per cent magnesium sulphate solution is placed over the puncture point on the finger. The bloi issuing from the wound mixes with the solution and smears are made from this mixture, which are then fixed and stained after Romanovsky-Giems The fixing and staining time should be doubled (compared with the blood smear staining time). Using a window to restrict the field of vision (like counting reticulocytes), 1000 erythrocytes and all thrombocytes that occ among them are counted in vision fields. Once the number of erythrocyt in 1 \A is known, the number of thrombocytes can be calculated in 1 calculated in 1 1 of blood.

Apart from the described indirect counting of thrombocytes, they c also be determined directly in a counting chamber. The blood is diluted a suitable solvent, e.g. by a 1 per cent ammonium oxalate solution. A phase contrast microscope is used for counting. This method is more accurate than indirect counting. In certain diseases of the haemopoietic organ thrombocyte counts are also necessary. Juvenile, mature, and old throi bocytes are distinguished. They also differ in size, shape, colour and structure; their degenerative forms appear sometimes.

Changes in the morphological composition of the blood should be us establish diagnosis of a disease together with the other findings of exemination of the patient.

Erythrocyte sedimentation rate (ESR). Erythrocytes do not clog ;ether in the stream of blood because they are all negatively charged. If a »od specimen is placed in a vertical vessel and an anticoagulating agent is added to it, erythrocytes gradually settle by gravity. Then they agglomerate o heavier groups which precipitate at a faster rate. Agglomeration is promoted by some protein components of the plasma (globulins, irinogen) and by mucopolysaccharides. Therefore, the processes which increase their accumulation in the blood are attended by acceleration of erythrocyte sedimentation. This condition occurs in most inflammatory ocesses, infections, malignant tumours, collagenoses,  nephroses, and N sue decomposition; to a certain measure, this acceleration is proporinal to the gravity of the affection. In certain diseases erythrocyte dimentation is not accelerated in their initial stage (epidemic hepatitis, phoid fever); in other pathological conditions erythrocyte sedimentation the is slowed (heart failure).

Erythrocyte sedimentation rate is not an independent diagnostic symptom it only indicates the activity of the process. It is important in this perfect in the diagnosis of tuberculosis, rheumatism, and collagenosis. hanges in the erythrocyte sedimentation rate do not always agree with      \ her signs of activity. For example, ESR lags behind the rate of temperature elevation and leucocytosis in appendicitis or myocardial infarction; its normalization is also slower than normalization of the mentioned symptoms. The normal ESR does not rule out the presence of      I isease which would be usually attended by anncreased erythrocyte alimentation rate. But it should be remembered that ESR does not in­case in healthy people.

The Panchenkov method of ESR determination is widely used in the Soviet Union. A Panchenkov capillary graduated in 1 mm (100 divisions) is used for the purpose. It is filled with a 5 per cent sodium citrate solution to    

half of full capacity (50 divisions). The solution is blown out onto a  watch glass or into a test tube. Using the same capillary, 100 mm of blood i taken from the punctured finger (2 times). To that end, the capillary is end horizontally and brought in contact with the issuing drop of blood: he blood is drawn in by the capillary force. The blood is then mixed with he reagent in the 4:1 ratio. The mixture is taken into the capillary, to the nark 0 (100 divisions), and placed in a Panchenkov stand, in a strictly verical position. The number of millimetres of a settled plasma column is noted in 60 minutes. The normal rate for men is 2—10 mm/h and for women 2-15 mm/h.

The morphological composition of the blood does not always show the changes occurring in the haemopoietic organs. For example, the cell com­position of  blood remains almost unaltered in aleukaemic form of leucosis despite significant changes in the bone marrow. M. Arinkin (1928) pro­posed asternal puncture for intravital study of the bone marrow. Owing to the simplicity and safety of the procedure, it is used for the study of almost all patients with diseases of the haemopoietic system. The Kassirsky needle is used for the purpose in the Soviet Union. This is a short thick-walled needle with a mandrin and a stopping device that prevents deep penetration of the needle. After the skin, subcutaneous fat and the periosteum are anaesthetized, the soft tissues are punctured over the sternum, at the level of the second or third intercostal space (or above the manubrium). Then the stopping device is fixed at a distance of 5 mm from the skin surface and the anterior plate of the sternum is punctured: the operator’s hand has a feeling of entering a cavity. The mandrin is now removed and a dry 10-20 ml syringe is attached to the needle. About 0.5 or 1 ml of bone-rnar-row is now aspired into the syringe and transferred onto a watch glass. If the bone marrow is mixed with an unknown quantity of blood, its com­position cannot be definitely determined. Using a blotting paper (or by in­clining slightly the watch glass), the blood is separated, and the small grains of bone marrow are carefully pressed against the glass to prepare a smear of the crushed marrojv. After fixation and staining (Romanovsky-Giemsa), not less than 500 elements containing nuclei are counted in the smear. A myelogram is then derived.

The marrow specimen can show upset maturation of the cells: increased number of juvenile forms or prevalence of primary undifferentiated elements, upset proportion between the red and white cells, changes in the total number of cells, presence ol ihe pathological forms, etc. Apart from the sternum, other bones (e.g. ilc bone) can also be used for taking the bone marrow.

 

Bone marrow specimen iorm

 

 

 

Low–cellular \bone marrow specimen

 

 

Megacariocite

 

More accurate information on the composition of the bone marrow is given by trepanobiopsy. A special needle (troacar) is passed into the iliac crest to cut out a column consisting of the bone-marrow tissue, which is then used for making histological preparations. The structure of the bone marrow remains unchanged in the preparations while the absence of blood makes it possible to evaluate its cells composition and to reveal focal and diffuse changes in it.

Enlarged lymph nodes are often punctured. It makes it possible to establish the character of changes in the cell composition and to verify the diagnosis of some systemic diseases of the lymph apparatus (lymphoid

Leucosis, lymphogranulomatosis, lymphosarcomatosis), to reveal metastases of tumours, etc. More accurate data can be obtained with biopsy of the lymph node. The puncture is made without anaesthesia, by a simple injectioeedle attached to a 10-ml syringe. The obtained material is used to prepare smears. The spleen is punctured by the same method. The pa­tient is asked to keep breath at the inspiration height to prevent possible injury of the spleen during respiratory movements. Combined study of cell composition of the bone marrow, spleen and lymph nodes reveals the rela­tions between these organs of the haemopoietic system and the presence of extramedullar haemopoiesis which develops in some affections’ of the bone marrow.

Coagulation of blood is a complicated enzymatic process, in which 13 plasma facto (I-XIII) and 12 thrombocytic factors (1 — 12) are involved. The plasma factors of bloc coagulation are as follows: I-fibrinogen-fibrin, H-prothrombin-thrombin, Ill-thrombi plastin, IV-Ca ions, V-proaccelerin, Vl-accelerin, VII-proconvertin, Vlll-antihaemophil globulin, IX-plasma thromboplastin component, X-Koller factor, Xl-plasma thrombopiast antecedent, Xll-contact factor, and XHI-fibrinase (fibrin-stabilizing factor). According to at activation sequence (“the cascade theory”), each plasma factor of the coagulation system is proenzyme which is activated by the preceding factor and, in turn, activates its successor, the to ensure a kind of a chain reaction.

The blood coagulation process can be divided into three phases. The first begins at the moment when the blood contacts the rough surface of the injured vessel to activate the first lii in the chain (contact factor, XII) and to complete formation of thromboplastin (factor 11 Thromboplastin is formed from the antihaemophilic globulin of plasma (VIII) with particiption of plasma factors XII, XI, X, IX, V, and three platelet factors in the presence of calcium ions.

The second phase of blood coagulation begins with formation of thromboplastin: t blood prothrombin (produced by the liver with involvement of vitamin K) is activated thromboplastin in the presence of the calcium ions, plasma factors VII and VI, and the thrombocytic factor to convert into an active thrombin. Thrombin acts on the fibrinogen blood to form fibrin. This is the third phase which ends by formation of a blood clot, i.e. t red thrombus. The next stage is the action of the fibrin-stabilizing factor of the fibrin. Unc the action of the 6th platelet factor, retractozyme, fibrin threads shorten to contract and cc solidate the clot, which accounts for a complete discontinuation of the bleeding.

In addition to the factors promoting coagulation, the blood contains also anticoagulai or inhibitors of blood coagulation which are responsible for the liquid state of normal blood. Each component of the coagulation system has its opponent inhibitor (antithromboplast antithrombin, anticonvertin, etc.). There are inhibitors to anticoagulants too. In physiological conditions, a change in any factor causes a corresponding change in its antagonist; the equilibrium of the two systems is thus maintained. Imbalanced increase in anticoagulant ac­tivity results in bleeding. Heparin is the most powerful anticoagulant. It inhibits all phases of blood coagulation, especially conversion of prothrombin into thrombin. Thrombocytic fac­tors play an important role in the described processes. Some of them promote coagulation of blood, and others activate anticoagulants.

After the blood clot fullfils its purpose, the reverse process is started, its dissolution. It is attained through the action of a complicated enzymatic fibrinolytic system, which in many respects is similar to the coagulation system. Fibrin of the clot is dissolved by the proteolytic enzyme fibrinolysin which circulates in the blood as an inactive profibrinolysin. It is activated by fibrinokinase (plasmic, tissue, and bacterial). There are the corresponding inhibitors of fibrinolysin and fibrinokinase: antifibrinolysin and antifibrinokinase.

It is clear that haemostasis is a very complicated phenomenon and it is V sometimes difficult to find the defective link in this chain of processes. There are many tests that can reveal predisposition to bleeding or thrombus formation and to find their causes. Classical tests are distinguished by which the general coagulation trends of a given blood can be determined and which are  used to examine all patients with haemorrhagic diathesis. There are also differential tests by which a missing factor can be found. The classical tests are used to determine (1) blood coagulation time; 2) thrombocyte count; (3) bleeding time; (4) retraction of blood clot; and (5) permeability of capillaries.

Coagulation time characterizes coagulability of blood in general without accounting for separate phases of the coagulation process ‘ Coagulation time increases in increased anticoagulation activity of blood or decreased concentration of procoagulants and shortens in the presence ” of the tendency to thrombus formation. The longest coagulation time (to several hours) is observed in haemophilia A. It does not change in certain haemorrhagic diatheses.

In order to evaluate coagulability of blood, a venous blood specimen is placed in a test tube and kept on a water bath at a temperature of 3C! At 30-second intervals, the test tube is inclined and inspected to see if the li­quid level is mobile. In physiological conditions, the blood coagulates in 5—10 minutes (Lee and White method).

Drop tests are widely used to determine coagulability of blood. A specimen of blood is taken either in a capillary pipette and the time when it loses mobility is determined, or a drop is placed into a moist heated chamber onto a paraffin-coated watch glass and the time, when the drop does not flow toward the edge of the inclined glass, is determined.

Estimation of bleeding time (by Duke’s method). The finger tip or an ear lobe is punctured by Franke’s needle or a blood lancet to a depth of 3 mm. The spontaneously issuing blood is removed at 30-second intervals \jy touching it with blotting paper. The normal bleeding time is 2-4 minutes. Since discontinuation of bleeding is associated with formation of a white thrombus, the test results depend on the number of thrombocytes and the ability of the vascular wall to contract, which is promoted by liberation of the vasoconstricting factor, serotonin, by thrombocytes ./The bleeding time in trombocytopenia is considerably prolonged and the number of blood drops removed by the blotting paper increases many times (Plate 29, a and b). If the capillary tone is abnormal the size of blood drops increases.

Clot retraction also depends on the number and activity of throm­bocytes since it occurs under the effect of retractozyme liberated by the blood platelets. A specimen of venous blood (3-5 ml) is placed in a graduated centrifuge test tube and placed in a thermostat at a temperature of 37 °C. The serum separated in 24 hours is removed and its volume is divided by the volume of the blood specimen to calculate the retraction in­dex which is normally 0.3—0.5.

Capillary permeability.-JKonchalovsky-Rumpel-Leede sign. A tourni­quet is applied to the forearm and changes occurring in the skin are as­sessed. If petechiae appear on the skin below the tourniquet, the test is positive. Application of a sphygmomanometer cuff and the appearance of more than 1 petechiae on the sJkin area of 1 cm² at a pressure of about 100 mm Hg is interpreted in the same way.

Cupping glass test. Air is evacuated from a cup applied to the skin (rarefaction of about 200 mm Hg) for two minutes. If the test is positive, petechiae develop on the skin under the cup. The number of petechiae shows the degree of affection of the vascular wall.

Pinch test. A haemorrhagic spot appears at the site of a pinch, which gradually increases in size and becomes more intense.

Mallet symptom. Ecchymosis develops on the skin after tapping with a percussion mallet.

Determining activity of the 1st phase of blood coagulation. The simplest test is the determination of time of plasma recalcification. The time of coagulation of oxalate plasma, after adding an optimum quantity of calcium chloride to it, is determined. (The oxalate plasma is prepared by mixing 9 parts of plasma with 1 part of a 1.34 per cent sodium oxalate solu­tion and separation of plasma by centrifuging.) The test characterizes blood coagulability in general. Its results somewhat differ from those of the whole blood coagulability tests, in which the formed element factors are also involved. The normal time of recalcification is 60-70 seconds.

The prothrombin consumption test characterizes the activity of those plasma factors which utilize prothrombin in the process of thrombin for­mation. The prothrombin time of plasma (see below) and serum is deter­mined. The higher the prothrombin consumption during plasma coagulation, the less is its amount in the serum and the longer it takes to coagulate, and vice versa. It follows that shorter time of prothrombin consumption test indicates disordered formation of thromboplastin.

Determining activity of the 2nd phase of blood coagulation. The activi­ty of the 2nd phase of blood coagulation (formation of thrombin) depends on prothrombin concentration. Its determination is difficult; the overall activity of the prothrombin complex (factors II, V, VI, VII, and X) is therefore established. The method consists in determination of the rate of oxalate plasma coagulation  after adding excess  thromboplastin and calcium chloride (Quick’s time). Since the time of coagulation depends on some conditions (thromboplastin concentration, temperature, etc.), the prothrombin index is usually determined: percentage ratio of the pro­thrombin time of the donor’s plasma to the prothrombin time of the pa­tient’s plasma (normally it is 80-100 per cent).

Heparin tolerance test characterizes the same phase of coagulation. The test consists in determining the deviation (withjespect to norm) in the time of oxalate plasma coagulation after adding heparin with subsequent recalcification. As the activity of the coagulants increases (tendency to , thrombosis) the plasma tolerance to heparin increases, and the time of plasma coagulation decreases. If the activity of the anticoagulants . predominates (tendency to bleeding), the time increases.

Determining activity of the 3rd phase of blood coagulation. This is the determination of fibrinogen by an equivalent content of fibrin.

Additional tests. Apart from the mentioned relatively simple methods, there are many complicated tests by which the activity of components of the coagulation and anticoagulation systems are determined. Two of them are now commonly used for the determination of the general coagulation tendency of  blood (tendencyto hypo- or hypercoagulation). The methods are known as thrombotest and thromboelastography.

Thrombotest. A 0.1 ml specimen of oxalate plasma is placed in 5 ml of a 0.5 per cent calcium chloride solution. Sedimentation of fibrin after a \ 30-minute incubation at 37 °C varies in character (from slight opalescence \ or the appearance of minutest fibrin grains to the formation of a firm clot), depending on the coagulating properties of blood. Seven degrees of throm­botest are distinguished, from which three correspond to hypocoagulabili-ty, two (4th and 5th) normal coagulability and two (6th and 7th) hyper­coagulability of blood.

Thromboelastography. The test gives a graphic representation of the entire process of spontaneous coagulation of unaltered (native) blood or plasma. A blood specimen is taken from the vein by a silicon-coated needle    . and placed into a small cell into which a rod bearing a disc is immersed. The cell is vibrated by an electric motor. The disc remains motionless till the blood specimen remains liquid. As the blood thickens, the disc become: engaged, and the rod with a mirror attached to it begins vibrating. A bean of light is reflected from the mirror and recorded on a sensitive paper in the form of a zig-zag curve (thromboelastogram). By measuring its separat portions it is possible to assess some properties of the coagulation process for example, the “reaction time”, which corresponds to the length of the 1st and 2nd phases of blood coagulation, the time of clotting (the 3r< phase), elasticity and strength of the clot, and some other indice ^; characterizing hyper- or hypocoagulability of blood (see Appendix). Summation of the findings of all mentioned tests gives a coagulograry characterizing the condition of the blood coagulation system.

X-RAY EXAMINATION

X-rays can be used to reveal enlargement of the mediastinal lymp nodes (lymphoid leucosis, lymphogranulomatosis, lymphosarcoma) an also change’s in the bones which occur in some types of leucosis and malii nant lymphoma (focal destruction of bone tissue in myeloma, boi destruction in lymphosarcoma, consolidation of bones in osteomyelosclerosis). Changes in the bone tissue are better revealed \ X-rays. The spleen is not seen during common X-ray examinatioin Splenoportography is a special technique which is used for examining the vessels of the spleen (see section on splenoportography).

 

ENDOCRINE SYSTEM AND METABOLISM

Methods of Examination

Inquiry

Complaints. The endocrine system has multiple effects on various bodi­ly functions and the patient’s complaints are therefore varied. The patient may complain of increased excitability, interrupted and superficial sleep, impaired memory, irritability, hyperhidrosis, chills, heart palpitation, noise in the ears, blood rush to the head, skin itching, increased thirst, and considerable wasting. When inquiring the patient, the physician can reveal

f some features of his nervous and psychic character that may suggest some endocrine diseases: e.g., fussiness, rapid movements, hasty speech, apathy, and flaccidity suggest thyroid dysfunction, while mental underdevelopment, and its degree—infantilism and cretinism.

Anamnesis. It is important to establish the direct cause of the disease. Strong emotions, fear, and psychic traumas are the predisposing factors for thyrotoxic goitre. Endocrine diseases often develop during sexual

^!     maturation, after childbirth, and during menopause.

The hereditary factor is also important in endocrine diseases, e.g. in diabetes mellitus. The endocrine function can be affected by some other diseases. Tuberculosis of the adrenal glands, for example, is the cause of their hypofunction (Addison’s disease).

 

Physical Examination

INSPECTION

Inspection of the patient is a valuable diagnostic procedure. Sometimes the diagnosis becomes clear at first sight. The patient’s appearance and some special features of his behaviour are quite characteristic in diffuse thyrotoxic goitre, myxoedema, acromegaly, nanism (dwarfism), pituitary cachexia, – Itsenko-Cushing   syndrome,   Addison’s   disease,   upset   fat     metabolism, etc.

Endocrine diseases, especially affections of the thyroid and pituitary glands, can alter the expression of the patient’s face. Patients with thyroid hyperfunction have large, wide open, protruded eyes; winkling is rare, the eyes are lustrous, and the patient’s face has the expression of horror or fear. The face of patients with thyroid hypofunction (myxoedema) is ound, without wrinkles, with motionless eyes; the general expression is lullness and apathy. The acromegalic face is characterized by protruding uperci Hary arches, abnormally large nose, lips, tongue and the chin; the bnormally large lower jaw has widely set teeth (diastema). Pituitary lypofunction is attended by obesity which gives the woman-like expression o the male face.

Neck. Inspection of the anterior surface of the neck can reveal the size >f the thyroid gland (its enlargement).

Height. Gigantism (over 195 cm) is mostly the result of anterior >ituitary hyperfunction (acromegalic gigantism) or hypofunction of the sex dands (hypogonadal gigantism). Dwarfism (the height below 135 cm) can )e due to hypofunction of the anterior pituitary lobe with preservation of : hildish proportions of the body, underdevelopment of the sex organs, and he absence of the secondary sex characters. The same symptoms can be ) observed in marked thyroid hypofunction with signs of myxoedema and mental retardation (to idiotism).

Skin. Pallid face with a yellowish hue is characteristic of myxoedema; he face is hyperaemic in Itsenko-Cushing syndrome (anterior pituitary lyperfunction); the mucosa and skin are bronze (especially skin folds, the palms) in patients with Addison’s disease (adrenal hypofunction). Dry and scaling skin is characteristic of thyroid and parathyroid hypofunction; the skin is dry and cold in hypothyroidism. The skin is smooth and moist in patients with hyperthyroidism. Thickening of the skin associated with hyper-rophy of its papillar layer is found in acromegaly. Oedema of the skin which is characteristic of hypothyroidism is due to its impregnation with mucinous substance, The Itsenko-Cushing syndrome is characterized by atrophy of the skin on the femur and the abdomen (red-violet striae). Scratching of the skin and furunculosis, cholesterol deposition in the skin of the eyelids is often observed in diabetes mellitus.- Nails are brittle in hypothyroidism and tetany.

Hair. Changes in hair is an important diagnostic sign in endocrine diseases. A female pattern of hair growth in men is typical of eunuchoidism, while male-type pilosis in women occurs in acromegaly and Itsenko-Cushing syndrome; falling of hair from the eyelids, brows, mustaches, and the head is characteristic of myxoedema.

Subcutaneous fat. Uniform distribution of fat over the entire body is characteristic of thyrogenic obesity, while deposition of fat mostly in the pelvic region (lower abdomen, buttocks, thighs) occurs in pituitary and pubertal obesity. Excess fat on the face and trunk is a sign of the Itsenko-Cushing syndrome. Excess wasting is observed in some forms of diabetes mellitus and thyrotoxic goitre. Cachexia is a sign of Simmonds’s disease which is due to the affection of the pituitary gland (pituitary cachexia).

Bones. Eunuchoidism is characterized by a delayed growth of the epiphyseal ends of long tubular bones. Acromegaly is marked by abnormal thickening of the enlarged bones of the skeleton.

Muscles. The hormone of the parathyroid glands is produced in defi­cient quantity and the blood calcium content is thus decreased. As a result, patients develop tonic convulsions (mostly of the flexor muscles). The pa­tient’s hand is flexed to give the specific appearance of the “obstetrician hand”. When the facial muscles are affected by convulsions, the face ac­quires the expression of a  forced smile. The muscles are developed in excess in acromegaly.

Congenital hypothyeosis in a child

 

  

 

   

 Appearance of patients with hypothyreosis

 

The thyroid and the testes are the only endocrine glands that are ac­cessible to direct inspection.

PALPATION

The thyroid gland-is studied by palpation. Tentative palpation assesses the density of the organ, the character of its surface, and the presence of nodes. Then follows special palpation. The examiner places four flexed fingers of both hands deep beyond the posterior edges of the ster­nocleidomastoid muscle, and the thumbs beyond the anterior edges of this muscle. The patient is now asked to make swallowing movements: the thyroid together with the larynx moves between the examiners thumbs. This method is used to reveal even insignificant enlargement of the thyroid gland that cannot be detected by common palpation. Mobility of the gland during swallowing, the presence or absence of pulsation, and tenderness of the thyroid can also be determined by this method. Palpation of one lateral lobe of the gland can be facilitated by pressing the thyroid cartilage on the opposite side. The thyroid isthmus is palpated by the sliding movements of the examining fingers in the direction of the sternal manubrium. The lower portion of the thyroid, which is concealed behind the sternal manubrium, maybe affected by nodes. In order to palpate them (for outlining their borders and assessing their consistency), the patient is asked to make swallowing movements, while the examiner’s fingers palpate the thyroid in the suprasternal notch.

In order to follow up changes in the size of the thyroid gland, it is im­portant to determine its size. The girth of the neck, the transverse dimen­sion of the thyroid and the size of its separate nodes should be determined. When measuring the girth of the neck, one end of the measuring tape should be fixed on the crest of the 7th cervical vertebra, the tape being passed over the most prominent part of the thyroid. When taking transverse measurements, the tape is placed beyond the outer posterior edges of the sternocleidomastoid muscles and passed over the anterior surface of the thyroid gland. The diameter of separate lymph nodes of the thyroid gland is determined by bow compasses with rounded ends.

Palpation gives a more detailed information on the structure of the skeleton and the condition of the skin of patients with endocrine diseases that were first revealed by visual examination.

Percussion can reveal a retrosternal struma (goitre).

Video:Thyroid_gland_palpation

 

AUSCULTATION

Sounds and murmurs can be heard over the enlarged thyroid in patients with thyrotoxicosis. These are explained by accelerated flow of blood and its intensified supply to the thyroid gland.

Laboratory studies

Determination of protein-bound iodine (PBI) in the blood serum is widely used to study the thyroid function because 90—95 per cent of protein-bound iodine is the iodine of thyroxin. The level of the protein-bound iodine in healthy adults varies from 315 to 630 nmol/1 (4-8 mg/100 ml). Figures below 275 nmol/1 (3.5 mg/100 ml) indicate hypothyroidism, and above 670 nmol/1 (8.5 mg/100 ml) hyperthyroidism. If high PBI persists for a year and does not vary with increasing content of thyroid hormones in the blood, it may be due to administration of contrast iodine-containing substances (for X-ray examination) and iodine therapy (saiodin, enteroseptol, mexase, etc.). The blood serum of patients with parathyroid hypofunction is examined for calcium and phosphorus; the content of these elements decreases in tetany.

Aldosterone and hydroxycorticosteroids are found in decreased quanti­ty in patients with diseases of the adrenal glands (Addison’s disease); the content of potassium and sodium salts increases in these patients. In suspected diabetes mellitus (and also in the, presence of this disease) the blood and urine are tested for sugar (see below).

 

DISEASES OF BONES, MUSCLES, ANp CONNECTIVE TISSUE. ACUTE ALLERGOSES

This is a very large group of diseases. In certain cases, affections of the osteo-articular apparatus, muscles or connective tissue are primary and their symptoms prevail in the clinical picture of the disease (although signs of affections of other organs or systems may join). In other cases, affec­tions of the bones, muscles or connective tissue are only secondary to some other diseases (metabolic disorders, endocrine diseases, etc.), and their symptoms only supplement the clinical picture of the main disease. Systemic affections of the connective tissue, diseases of bones, joints, and muscles make a special group known as collagen diseases (collagenosis, dif­fuse connective tissue disease). These diseases are characterized by allergic inflammation of the connective tissue and its derivatives. Immune and auto-immune disorders are of certain importance in the pathogenesis of many diseases, but they are decisive in the pathogenesis of the collagen diseases.

Collagen diseases are divided into four major collagenoses: rheumatoid arthritis, systemic lupus erythematosus, systemic scleroderma, and der-matomyositis. Rheumatism is close to these diseases with respect to its pathogenesis.

Among diseases of the osteoarticular apparatus, muscles and connec­tive tissue, differentiated are diseases of inflammatory nature of various aetiology (arthritis, myositis, etc.), mostly metabolic and dystrophic affec­tions (arthrosis, certain myopathies, etc.), tumours, and congenital developmental abnormalities.

Methods of Examination

Inquiry

Complaints. Patients with diseases of the bones and muscles and with systemic affections of the connective tissue can produce various com­plaints. These would be commonly pain in the joints, spine, or muscles, hindered movements in the morning, sometimes muscular weakness, and elevated temperature. Symmetrical affections of minor joints of the hands and soles, their tender articulation (active and passive) and also tender palpation are characteristic of rheumatoid polyarthritis. Major joints (wrist, knee, elbow, hip) are affected less frequently in this disease. Pain becomes more intense by night, in cold and damp weather. At later periods of the disease, the joints are distinctly disfigured, and their articulation is limited (to ankylosis). A frequent complaint is difficult and limited articulation and movement in the morning; the movements become easier by the end of the day. Rheumatism and arthrosis deformans are characterized by a distinct tendency to affection mainly of the major joints. In arthrosis deformans, pain develops mainly under load on the affected joint (in walk­ing, stepping on the affected leg). Pain intensifies by the evening as a result of daily exercise. In ankylosing spondyloarthritis (Bekhterev’s disease), pain is localized in the spine and the sacrolumbar articulations. Pain develops after a long stay in a fixed position (usually during night sleep). At later stages of trie disease when changes in the spine become pronounc­ed, pain becomes permanent; it occurs not only during night but also in physical exertion and during weather changes. Specific changes in the spine of a patient can be revealed by the physician at first sight. In rare cases, the joints are also involved in this disease.

Rheumatoid polyarthritis is characterized by the predominant affection of the major joints and by the “wandering” character of affection: various joints are involved one after another, while pain in the previously affected joint disappears (within a few days or weeks) and articulation is restored. Another specific feature of rheumatoid polyarthritis is that all changes in the affected joints and periarticular tissues disappear and leave no trace after the acute rheumatic process abates.

Acute attacks of pain, mainly in the metatarsophalangeal joints of the great toes (less frequently in other joints), which arise mainly during night and predominantly in the aged and middle-aged males, can be a symptom of gout, the disease in which the purin metabolism is upset.

Thus, if a patient complains of pain and difficult movement of joints, the character of this pain should be studied thoroughly to determine its location, intensity, lenght, effect of exercise and other factors that can pro­voke pain, etc.

Muscular pain also differs in its character. Pain can be disseminated to indicate involvement of the entire muscular tissue. Acute attacks of pain in this or that group of muscles that last for several days (often after exposure to cold) suggest myositis. Pain in the calf muscle during walking (usually in the presence of marked atherosclerosis of the arterial vessels in various organs, in frost-bitten legs, in heavy smokers) is characteristic of stenosing arteries of the lower extremities (due to atherosclerosis, obliteratingendar-theritis, and certain other diseases). Pain discontinues when the patient stops walking (the syndrome of intermittent claudication). The part would often complain of cold in the legs which makes him wear woo socks /and winter boots even in warm weather. Muscular pain is all symptom of trichinelliasis, cysticercosis, or myositis of infectious, occu tional (chronic exposure to low or high ambient temperature, vibratior other harmful industrial factors), and traumatic origin. It is important determine localization, intensity, character, and duration of the pain.

Elevated temperature and various skin lesions (petechia, erythema, ticaria, etc.) are frequent symptoms of systemic diseases of the connect tissue, the so-called collagenoses, and also allergoses. A rapidly develop (without apparent cause) local oedema of the skin and subcutaneous is frequent in Quincke’s disease (allergic oedema attended by skin itch and burning; this may be caused by food, bacterial or other allergy).

Muscular weakness (hypotonia) develops not only in prolonged (immobilized patients with grave diseases) but also in some neurology diseases (myatonia, myasthenia, progressive muscular dystrophy, el Each of these diseases has its special features. Myasthenia, for example characterized by pathological muscular fatigue. Contractions of a mu may first be quite normal, but in repeated movements the muscular at decreases to complete loss of contractile power. After a short rest, the ache again becomes capable of contracting. Muscles lifting the upper eye and muscles participating in swallowing and mustication are usually afected in the first instance.

Weakening of active muscular movements is called paresis, whi complete loss of power to perform movements is known as paralysis. Paresis and paralysis may affect any muscle or group of muscles in presence of impaired innervation. Clinicists (internists included) commonly observe patients with affected innervation of muscles of i one extremity (monoplegia); sometimes both legs are paral; (paraplegia), or the extremities on one side are only affected (hemiplei Tetraplegia (paralysis of all four extremities) occurs in rare cases. Para and paresis can develop due to affection of peripheral nerves, spinal  (injury, compression, tumour growth, etc.), of certain parts of the brail thrombosis of the cerebral vessels, e.g. in atherosclerosis, embolism cerebral haemorrhages). Spastic paralysis with subsequent atrophy oil paralysed muscles occurs in affection of the central neuron.

The patient sometimes complains of cold and pale fingers (in rare c of the ear or nose). This may occur at low ambient temperatures, inju and psychic stress. This is attended by pain and hyposensitivity of the to pain and temperature variations; this condition may develop after a tack of hyperaesthesia.  Such attacks are characteristic of Rayna disease (vasomotor neurosis). This condition is often the first symptom of i grave collagen disease, systemic scleroderma.

Anamnesis. Information concerning the onset and development of the lisease should be collected. Many chronic diseases of bones and muscles level of insidiously and progress slowly. The disease becomes apparent on-y at later periods. Acute vigorous onset is characteristic of rheumatism often in 2-2.5 weeks following tonsillitis, scarlet fever or acute espiratory infection), some forms of rheumatoid arthritis, and infectious thritis (caused by brucellosis, dysentery, gonorrhoea, etc.). Acute affection of muscles occurs in myositis, acute paralysis, including paralysis massociated with injuries. Hemiparesis in patients with atherosclerosis or irterial hypertension of any origin occurs not infrequently. Hemiparesis levelops due to thrombosis of the cerebral vessels, cerebral haemorrhagesmitral heart diseases concurrent with cardiac fibrillation and throm-ioendocarditis (due to embolism and arterial obstruction) and in some there diseases. Nodular periarteritis (mainly in the young) and systemic opus erythematosus begin acutely only in rare cases.

In some cases, it is possible to establish the factor that provoked the disease of the joints and systemic affections of the connective tissue. In lost cases, these diseases are preceded by an infectious disease or over-ooling of the body; sometimes the disease follows irrational use of ledicinal preparations (sulpha drugs, antituberculosis preparations, antibiotics, vaccines, sera, etc.), or develops due to perverted hypersensitivity ) these preparations.

Anaphylactic shock may develop in patients with acquired or con-enital hypersensitivity to certain medicines given parenteral-‘ or when carrying out some tests, e.g. Pirquet, or Mantoux test. Some ledicines can cause anaphylactic shock due to a contact with the mucosa :ye conjunctiva, mouth mucosa). But a slow development of an allergic :action to medicinal preparations (antibiotics, sulpha drugs, butadione, liamine, procaine, etc.) is more frequent: skin itching, dermatitis, ur-caria, fever, arthralgia, myalgia, Iymphadenopathy and other types of ledicamentous allergy develop in several days. The remarkable advances i pharmacology help control many diseases, but they also bring along )me negative effects, e.g. development of the so-called medicamentous iseases. Therefore, when questioning the patient, it is necessary to find at if he took some medicines, and if he did, then for what diseases, and hat was the allergic reaction, if any.

A certain (unknown) role belongs to the hereditary predisposition of le patient to certain diseases of the bones and muscles, systemic diseases F the connective tissue, and various allergic affections (bronchial asthma, urticaria, etc.).

 

Physical Examination

INSPECTION

A glance at a patient can sometimes be enough to assess his health and diagnose the disease, e.g. anaphylactic shock, an attack of asthma, skin le­sions such as erythema, urticaria, or local angioneurotic oedema (usually localized on the face), and suggest the allergic nature of the affection. Changes in the skin become more pronounced in grave cases: vesicles and eveecrotic lesions develop on the skin and mucosa.

The posture of the patient, e.g. a marked kyphosis of the chest in com­bination with lumbar lordosis and limited mobility of the spine (the trunk of the patient is fixed in the inclined “position of a beggar”) suggests ankylosing spondyloarthritis (Bekhterev’s disease). Affections of the spine, joints, acute inflammation of muscles (myositis) limit the patient’s mobili­ty and sometimes immobilize him completely. The gait of the patient is quite informative for diagnosis. The paralytic gait of a patient with hemiplegia is characterized by the dragging limb. Paretic gait is characterized by slow movements of the patients and shuffling. It occurs in contracture of the extremities, paresis of the spinal origin. Unilateral affec­tion of joints of the lower extremities makes the patient spare the affected limb (limping on account of pain). It should be remembered that the hip joint is commonly affected in tuberculosis (tuberculous coxitis) usually in children; at later stages of the disease, ankylosis develops, the growth of the affected extremity is delayed, and the muscles become atrophied. Acute gonitis in adults can be of gonorrhoeal nature. Deranged innervation of muscles (paralysis, paresis of various nature), congenital myopathy (a group of diseases that are the subject of detailed discussion in the course oervous diseases) are also important for the gait of a patient. Patients with grave disorders of muscular innervation are completely immobilized.

 

Deformation of fingers in rheumatoid arthritis

 

Deformation of fingers as “swaeck”

 

Ulnar deviation in rheumatoid arthritis

 

Deformation of fingers as “swaeck”

 

Deformation of fingers as “swaeck”

 

Deformation of fingers as “swaeck”

 

Ulnar deviation of the wrist in RA

Heberden’s nodules in ostheoarthrosis

 

 

Typical deformation of iners in ostheoarthrosis

Acute arthritis in gout. Typical location

Tophuses in gout

Marked deformation of small joints of the hand and foot is characteristic for rheumatoid arthritis. Disfigured terminal phalanges of the fingers with sclerotically changed skin on them (with necrosis in grave cases), or specific stretching folds round the mouth, especially in young women, suggest systemic scleroderma (collagen group of diseases). Cramped muscles (usually flexor muscles) are sometimes revealed on in­spection of the patient (development of contracture).

Erythema of the face skin, butterfly distribution of eruptions on the forehead (also mostly in young women) suggest a grave systemic di­sease of the connective tissue—systemic lupus erythematosus. Focal sclerotic changes on the skin of variable size are characteristic of local scleroderma When examining the skin by palpation, the physician can reveal in­creased dryness, e.g. in systemic scleroderma, indurative oedema, and (at later stages of the disease) atrophy of the skin and focal calcinosis of soft tissues, mainly of the fingers and around major joints. Consolidation of muscles may occur in systemic scleroderma and dermatomyositis. The muscles are also consolidated and become tender in ordinary myositis. In the presence of Raynaud’s syndrome, palpation confirms abnormally low temperature of the skin of the extremities, especially of the terminal phalanges of the fingers.

Palpation of the joints reveals hyperthermia and oedema of the skin around them (in acute affections), tenderness and deformities of the joints. A thorough palpation can show whether only the joint or the surrounding soft tissues are also involved. In some cases, palpation can reveal that, despite tenderness of the joints and pain in them during movements, the joints are not affected by pathology.

Palpation is also used to study passive mobility of various joints; limited activity of joints can be due to pain in arthritis or arthrosis, and also in ankylosis (i.e. in articular immobility). In the presence, of in­complete ankylosis, the movement may first be unobstructed, but then sud­denly discontinue as if hindered by some insurmountable barrier. Special diagnostic techniques are sometimes used. In cases suspected for coxitis (inflammation of the hip joint), overextension of the stretched leg should be tried. The patient lies in the prone position. The movement of the af­fected leg is limited in coxitis due to developing pain and reflex muscular contracture. Flexion and rotation in the affected joint should be tried with the patient lying on his back. In order to measure accurately the angle be­tween two articulating bones through which an affected leg can move, a special instrument,  known as a goniometer,  is  used.   It should be remembered that the joint function can also be limited by cicatricial shrinkage of muscles or tendons due to past myositis, inflammation of ten­dons or their sheaths, or wounds. Inspection of the skin of the extremities, palpation of the muscles and tendons can reveal the cause of limited ar­ticulation. Palpation of the joint can reveal fluctuation in the presence of acute inflammation with ample transudate in the joint, or in the presence of purulent exudate.

By giving passive movements to all joints one after another and by palpating the muscles, it is possible to determine their tension. Contractile muscular tension, which depends on dysfunction of the lower motor neuron, and plastic tension which shows the condition of the internal medium of myofibrillae, are distinguished. Muscular hypotension and hypertension are possible. Hypotonic muscles are flaccid to the touch, the I belly of long muscles is not pronounced, passive movements are possible in the full extent, and sometimes even in a greater extent than of normal mus-1 cle. The joints are loose. When the muscle is passively stretched, the ex­aminer does not feel any muscular resistance. Muscular hypotension occurs mostly in affections of the peripheral nerves and prolonged muscular inac­tivity (e.g. when the patient keeps his bed for a long period for some grave disease). Muscular hypertension arises as a result of increased reflex muscular tension in the presence of affected pyramidal tracts; the muscles are firm and difficult to stretch passively; muscular resistance increases with the speed and abruptness of passive movements.

In order to obtain a complete impression of the muscular condition, the force of muscles should be assessed. Two methods are used for the purpose. The patient may actively resist the physician’s attempt to flex or ex tend his extremity (static force), or, on the contrary, the patient tries to overcome the resistance of the physician’s hand (dynamic force). There an special instruments, dynamometers, and dynamographs which determine the muscular power of various groups of muscles.

X-RAY EXAMINATION                         

X-rays reveal calcification of soft tissues, e.g. in systemic scleroderma. But the X-ray examination is most valuable in diagnosis of diseases of bones and joints. Radiographs of bones and joints are usually taken. A new technique known as electroroentgenography is now used by which the picture is takeot on an X-ray film but on special paper. In order to reveal pathological changes, pictures of symmetrical bones and joints are usually made at least in two projections. The analysis of X-ray pictures reveals the proportions of the bones, their shapes, inner structure, and the condition of the joint slit. Osteoporosis (rarefaction of bone tissue), the presence of focal defects of the bones (in tumours, their metastases, etc.), osteosclerosis (consolidation of bone tissue in chronic haematogenic osteomyelitis, etc.), deformities of bones, changes in their articulation (narrowing or dilatation of the joint slit, dislocation, incomplete disloca­tion, etc.) and other pathological conditions can be detected by X-rays.

Each disease is characterized by a certain X-ray picture of changes in bones and joints. It should be remembered that bones are also affected in some endocrine diseases (hyperparathyroidism, acromegaly), prolonged treatment with glucocorticosteroids (osteoporosis develops), in the last term of pregnancy, in metabolic disorders, and in many other cases which, at first sight, might have no direct relation to skeletal affections. System scleroderma, for example, is characterized by osteolysis (resorption bones) of distal phalanges of the fingers and toes, and osteoporosis, mail epiphyseal one. This sign sometimes helps differentiate this disease from other collagen diseases.

 

 

X–ray changes in wrisrs of patient with RA: paraarticular osteoporosis, narrowing of joint sleat, usuras

 

Biopsy

Biopsy is indicated in cases suspected for tumour, for the determination of the character of muscular affections in systemic myopathies and in a lager diseases. In systemic lupus erythematosus study of  bioptate of I synovial membrane of the joints, liver, and kidneys helps reveal changes typical of a given disease. Lupus nephritis, haematoxylin bodies, and I “wire-loop” phenomenon are especially specific. Biopsy of the synovial membrane of joints, rheumatoid nodes (rheumatoid granuloma) is of gr importance for diagnosis of rheumatoid arthritis. Amyloidosis, which secondary to this main disease, can be revealed by biopsy of the kidney gum or rectal mucosa. Biopsy of the skin, and in some cases of the lyre nodes, is of great importance for the diagnosis of collagen diseases.