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
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 deter- mined. Pain of renal origin often localizes in the lumbarj^egion. If the , ureters are affected, the pain is felt by their course. If the bladder is involvVed, pain is suprapubical. Radiation of pain into the perineal region is Vfc 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 -VDull and boring pain in the lumbar region occurs in acute glomerulonephritis, abscess oi’lhe 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. i 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 usuallKJfflihiteral. 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 th presence of nerve fibres (carrying the impulses from kidneys, ureters, se organs and the corresponding skin zones) in the immediate vicinity of th relevant segments of the spinal cord (DX-DXI1 and L,-Lu). 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 pai of other aetiology would usually lie quiet in their beds (movements may ii tensify the pain).
The conditions promoting pain should be established. For exam pi pain iephrolithiasis can be provoked by taking muchjiquid, jolting nu tion, 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 tl pain. For example, atropine sulphate, hot water-bottle or warm bath he in renal colic. Since these remedies only help in spasmodic pain by remo ing spasmTof the smooth muscles, their efficacy in renal colic confirms tl leading role of the ureter contraction in the pathogenesis of this pain. Pa of the renal colic-type in patients with movable kidney may lessen wi changing posture: urine outflow improves with displacement of the kidne “” 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 i other analgesics.
Many renal diseases are attended by deranged urination: changes in tl daily volume of excreted urine and in the circadian rhythm of urinatioi
Secretion of urine during a certain period of time is called diurest Diuresis can be positive (the amount of urine excreted exceeds the volur of liquid taken) or negative (the reverse ratio). Negative diuresis is observi in cases of liquid retention in the body or its excess excretion through tl skin, by the lungs (e.g. in dry and hot weather). Positive diuresis occurs resolution of oedema, after administration of diuretics, and in some oth cases. Deranged excretion of urine is called dysuria.
Increased amount of excreted urine (over 2
Persistent polyuria with low specific gravity of urine (hyposthenuria) is ually a symptom of a severe renal disease, e.g. chronic nephritis, chronic elonephritis, renal arteriolosclerosis, etc. Polyuria in such cases indicates e 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 aying in a hot and dry room, in excessive sweating, intense vomiting, pro-ise diarrhoea, and during decompensation in cardiac patients. But in cer-in cases oliguria is the result of diseases of the kidneys and the urinary acts (renal oliguria), such as acute nephritis, acute dystrophy of the dneys in poisoning with corrosive sublimate, etc.
A complete absence of urine secretion and excretion is called anuria. .nuria persisting for several days threatens with possible development of raemia and fatal outcome. Anuria may be caused by the deranged secre-on of urine by the kidneys (secretory anuria) which occurs in severe form f acute nephritis, nephronecrosis (poisoning with sublimate or other ephrotoxic substances), transfusion of incompatible blood, and also sonW enerai diseases and conditions such as severe heart failure, shock, or pre use blood loss.
In certain cases the secretion of urine is normal but its excretion is ibstructed mechanically (obstruction of the ureters or the urethra by a :alculus, inflammatory oedema of the mucosa, proliferation of a malig-mnt tumour). This is called excretory anuria. It is usually attended by itrong pain in the loin and the of the renal pelves
Renal (secretory) anuria can be of reflex origin, e.g. in severe pain (con-;usion, 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 morejhan once. In the presence of pollakiuria the patient feels the desire to urinate during both day anj Lnight. 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, ke.i at rest (cardiac nycturia). Nycturia may concur with polyuria in renal dysfunction, at theTinal stage of chronic glomerulonephritis, chronic pyelitis, vascular nephrosclerosis, and other chronic renal diseases (rerial1 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 unpleas miting, and diarrhoea. All these phenomena are associated with retention in thebody 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 ai;uie_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,v. 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 chaiacter 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 wo ing conditions, drafts, work in the open, acute cooling of the body bef 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 h< establish the tuberculous nature of the present disease of the kidneys.
It is necessary to establish if the patient has some other diseases t might cause affections of the kidneys (collagenosis, diabetes mellitus, i tain diseases of the blood, etc.). Various chronic purulent dise£ (osteomyelitis, bronchiectasis) can be the cause of amyloidosis of kidneys. Occupations associated with walking, riding, weight lifting, e can have their effect on the course of nephrolithiasis and provoke atta ef 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 pregna 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 gn ty of the patient’s condition. Very grave condition with loss of c sciousness may be due to severe affections of the kidneys attended by re , insufficiency and uraemic j?pma; the condition may be satisfactory or v moderate gravity (in milder cases). It is necessary to pay attention to t 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 jhe presenxe of rena[jcolic^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 involvem 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 patholoj oedema affects the upper and lower extremities and the trunk (anasarc
Patient with renal oedema.
The colour of the patient’s skin is also important. Oedematous skin Iironic nephritis is pallid due to the spasm of skin arterioles, and anaerruV ‘hich attends this disease. The skin is wax-pallid in amyloidosis and lipoid ephrosis. It should be remembered that in cardiac oedema (as distinct^ rom renal oedema) the skin is more or less cyanotic.
When inspecting a patient with chronic nephritis, it is possible to ibserve 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 iremicus). All these signs characterize chronic renal insufficiency uraemia).
Inspection of the abdomen and the loin does not usually reveal any toticeable changes. But in the presence of paranephritis, it is possible to totice swelling on the affected side of the loin. In rare cases, an especially arge tumour of the kidney may be manifested by protrusion of the ab-iominal wall. Distended bladder can be protruded over the pubic bone in hin 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 prelum and pronounced
.
Palpation of the right kidney of the lying patient
Palpation of kidney in recumbent and vertical position of a patient
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-
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:shapedjbfldy 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 diffe dating 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 slij inclined forward.
Palpation can be used to diagnose ptosis of the kidneys. Three deg of nephroptosis can be distinguished: the lower pole of the kidney ca palpated in cases with ptosis of the first degree; the entire kidney cai 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 tr ,degree ptosis.
Palpation is “also used to examine the bladder. If it contains much ui especially in persons with thin abdominal wall, the urinary bladder cai palpated over the pubic jone as aplastic fluctuating formation. If bladder is markedlyllistended, its superior border reaches the umbilic
Tenderness in palpation of the ureter along its course and sensitive over the kidneys (sensitive to pressure exerted in the angle between the I rib and the longissimus thoracic muscles) is of certain diagnostic im , tance. The area overlying the ureter extends on the anterior abdominal < between the superior ureter point (at the edge of the rectus abdominiscle at the level of the umbilicus) and the inferior point (at the interseel 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 jiye tympany. Dullr 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 (Fig. 103). If the pati feels pain, the symptom “is positive (Fasterhatsky’s symptom). This syn torn is also positive iephrolithiasis, paranephritis, inflammation of pelvis, and also in myositis and radiculitis. This decreases the diagnoi 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 para to the pubic bone.
Determining Pasternatsky’s Symptom.
Instrumental and Laboratory Methods
URINALYSIS
tie study of urine is important for establishing a diagnosis of and config on the course of the pathology. Various pathological processes oclg in the kidneys and the urinary tracts have their effect on the properif 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
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. Determinationsf the specific gravity of the urine is of great clinical importance becauseMt 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-
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 whicbupH_Qf 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 glucose in urine. The urine of a healthy person cont very small quantity of glucose (0.03—0.15 g/1) which cannot be detecte 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 thres (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 ri carbohydrates (alimentary glycosuria), following emotional stress, ant ministration of some medicines (caffeine, corticosteroids). Less frequf renal glycosuria associated with disturbed resorption of glucose ir es: glycosuria develops in the presence of normal amount of sugar in lood. As a primary disease, glycosuria occurs in he form of renal tes. Secondary renal glycosuria occurs in chronic nephritis, nephritic
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 callf^ ed 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 vary-ln8 ^tensity) is another evidence of non-glomerular haematuria.
kihree-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. T swell in the urine of low specific gravity. Leucocytes in the urine c
healthy person are usually neutrophils and their amount is insignifican 1-
The degree of leucocyturia doesjioLalways correspond to the gra affection in chronic pyelonephritis. In the absence of active inflamn process, the quantity of leucocytes in the urine may remaiormal method of supravital staining is widely used now. It was proposed ir by Sternheimer and Malbin. Depending on their morphological prop leucocytes are coloured either red or pale-blue by a specia (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 wr urine precipitate to create low osmotic pressure.
Increased number of “active leucocytes” suggest activation of ii mation 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 nucleui he 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 pelves or the bladder. Cells of renal (cuboidal) epithelium of :s are rounded or polyhedral; they are small (slightly larger than :ytes) and have a large, eccentrically located nucleus; their granularity rse. 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 dneys, and also of fever, toxicosis, and infectious diseases. tsts 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
Von-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 dual :tion 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 frofn 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 gravitys 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). Combina-tion of polyuria with low specific gravity of the urine and nycturia is a specific sign of renal dysfunction.
Dilution test. The patient is given to drink 1-1.5 1 of water or thin tea within 30-45 minutes and then the urine is collected at.3^knjnute intervals during 4 hours. The portions are measured and their specific gravity deter- mined. A normal individual would eliminate about 75 per cent of the taken liquid during four hours, while the specific gravity of the urine decreases to 1.003-1.001. The firit ^portions will be larger and their specific gravity ‘ lower. A more accurate method includes also calculations where the amount of liquid taken is referred to the body weight: 22 ml of liquid is given per kg body weight.
If the excretory function of the kidneys is decreased, the amount of urine excreted during 4 hours is markedly less than that of liquid taken; the / specific gravity in all portions is about the same, but not below 1.006-1.007. If the renal function is upset significantly, the specific gravity of the urine in all portions is 1.009-1.011, which corresponds to the specific gravity of the primary urine. The dilution test is contraindicated in oedema and hypertension.
Urine concentration test. The patient receives no fluids for 36 hours (nor food containing much liquid). Urine is collected at 3-hour intervals during 24 hours (8 specimens). The volume and specific gravity of each specimen is determined. The specific gravity of the urine of a healthy individual will in these conditions be not lower than 1.028. If the specific gravity of thus obtained urine does not rise over 1.022, this indicates impaired renal function.
The urine concentration test is valid when applied to cases where the daily diuresis does not exceed 400 ml. The test is contraindicated in acute inflammatory processes in the kidneys, in cardiovascular and renal ciency, and in essential hypertension.
The renal function can be assessed by studying glomerular fill renal plasma flow, tubular transport of certain substances (e.g. reabsorption), secretion of extraneous substances, urea and electro cretion in the urine. It is possible to reveal and assess the degree of r sufficiency by studying concentration of urea, indican, residual ni creatinine, potassium, sodium, calcium, magnesium and phosphate blood (see Tables 7 and 8 of the “Appendix”).
Renal insufficiency arises in cases where the mass of the active chyma is 20 per cent (and lower) of the normal weight. The detenr of the mass of the active nephrons is thus important to assess tl function. The measure of active nephrons is the maximum reabsor) glucose (normal 300—500 mg/min) and the glomerular filtration ra mal, 65-120ml/min).
Clearance tests are now widely used to study the renal function ing to Van Slyke. Glomerular filtration and tubular reabsorption c can be measured by clearance tests with substances that are not resc liberated in the tubules. This means that these substances enter uri by glomerular filtration. Once we assume that a given substance co in a minute volume of plasma passes entirely into a minute vol urine, i.e. the plasma is completely cleared of this substance, the amount is then equal to the amount passed with urine. The filtered ty of substance is equal to the product of glomerular filtration (F] concentration in plasma (P). The quantity excreted with urine is ( the product of the urine minute volume (V) and the concentratior substance in the urine ((/), i.e, FP – UV. Hence
The U, V, and P values can be found clinically and used for th mination of F that characterizes the volume of plasma which is cor cleared of the given substance during one minute. This volume i clearance.
If a substance that is filtered in the glomeruli but is not rcabsc liberated in the tubules is used for the assessment of renal functi clearance of this substance is actually equal to glomerular filtratior this phenomenon, Rehberg proposed a test for studying the am filtration by endogenic or exogenic creatinine.
If one assumes that creatinine content of plasma and glomerulai is the same, it is possible to determine the degree of concentratioi glomerular filtrate as it passes the tubules. In other words, not of filtration but also of reabsorption can thus be determined age of reabsorbed water):
(F/r-, V) X 100
F ( liealthy individuals the amount of glomerular filtration is
ml. The percentage of reabsorbed water is 98.5-99.
Renberg test can be carried out with additional administration of xe and liquid, or without it. The second version is used more fre Blood is taken from the vein of the patient on a fasting stomach itinine concentration is determined. Urine is collected during 2 or
i. Diuresis is measured thoroughly and creatinine content determine , using the formula given above, the amount of glomerular filtra-i reabsorption percentage are calculated. Renal failure develops, glomerular filtration decreases gradually to low values as 5-2-1 ml/min. Tubular reabsorption changes less y to decrease in cases of pronounced insufficiency to 80-60 per itances that are not only filtered in the glomeruli but also secreted tubules give a mixed clearance, e.g. filtration-reabsorption or n-secretion clearance. This clearance is used to assess the renal / i in general (rather than its separate function). Clearance of some — ;es (diodrast, phenol red, para-aminohippuric acid, etc.) is so high v ctically approaches the renal blood flow, i.e. the amount of blood sess the kidneys during one minute. The renal blood flow can thus mined by the clearance of these substances, determination of glomerular filtration is of great clinical mce and is one of the most popular methods for quantitative study jnal function. The prognostic value of the method increases if it is Follow-up studies. Thus, persistent decrease in glomerular filtration — 50 mg/min during 18-24 months following acute ilonephritis suggests the conversion of the acute process into the disease.
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 ter minal 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 lym-‘ phogranulomatosis 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^ften 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. TbeseV 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 ir matory 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 brittl their ends break.
Changes characteristic of some diseases of the haemopoietic systei 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 shoul palpated to examine the bones: palpation of flat bones or epiphys( tubular bones (and also tapping over them) is painful in the presenc marked hyperplasia of the bone marrow.
Palpation of the lymph nodes and the spleen is however more ir mative. 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 ps 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.
nlarged 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-
One or several notches on the anterior edge of the spleen can be a jated 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.
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
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.).
The concept of a reticular ceil as a source of all cell elements of the blood has undergone a substantial revision in re%ent years in connection with advances in haematology. The haemopoietic scheme is now described as follows.
The first class of polypotent precursor cells is represented by the stem cell. The stem cells are self-sustaining, characterized by rapid proliferation and differentiation.
The second class of partly determined polypotent precursor cells is represented by precursors of lymphopoiesis and haemopoiesis; their self-sustaining power is limited; the cells are found in the bone marrow.
The third class of unipotent precursor-cells includes colony-forming cells (precursors of granulocytes and monocytes), erythropoietin-sensitive cells, precursors of B-lymphocytes and T-Iymphpcytes precursors
The fourth class includes morphologically identifiable proliferating cells; thefifth class includes maturating cells and the sixth class mature cells with a limited life cycle. The cells of the sixth class are mainly delivered to the peripheral blood.
The cell composition of the blood of a healthy individual is constant and any changes are therefore diagnostically important. But minor changes in the blood can be observed during the 24-hour period: after meals, exercise, etc. In order to remove these interfering factors, blood specimens should be taken under the same conditions.
Taking blood specimens. The study of blood begins with obtaining it specimen. Blood is taken from the 4th finger of the left hand. The finger first disinfected by a mixture of alcohol and ether. The skin on the side c the first phalanx is then punctured by a blood lancet to a depth < 2.5-
Determining haemoglobin. There are the following three major grou of methods for determining haemoglobin} colorimetric (widely used practical medicine), gasometric, and determination by the iron contain in the haemoglobin molecule. Sah’i’s method of estimating haemoglol (1895) was widely used until recent times.
J”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 inixi 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
against the strips. A well-w; and wiped glass is ground-in by reciprocating sliding movements u ntil 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 iver 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).
iere 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 es (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..
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here 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 tly 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 erythrocites
Once 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-
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-
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 absol amount 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 h< ing of wounds.
The regenerative shift to the left occurs most frequently in the presei 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 neutropl 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 prepa tions.
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 Th 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 jand 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 c”id 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 varia- J tion 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. HighVeticulocytosis 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-
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 mois^chamber (a Petri dish containing a piece of wet blotting paper). The smeaHs kept there for 5 minutes and then removed and allowed to dry.
The smear is inspected with an immersion system. Mature erythrocytes ai 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 mo 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 tl microscope is diminished by placing a special window in the eye-piece. Tl total number of erythrocytes and reticulocytes is counted in the field of \ sioiK 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 bloo Using the Romanovsky-Giemsa staining technique, the central part, tl 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 prepar tions, 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 magnesiu 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 frc this mixture, which are then fixed and stained after Romanovsky-Giems The fixing and staining time should be doubled (compared with the blo< 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 erythrocyl in 1 \A is known, the number of thrombocytes can be calculated in 1 /tl ai 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 phs contrast microscope is used for counting. This method is more accun than indirect counting. In certain diseases of the haemopoietic orgai thrombocyte counts are also necessary. Juvenile, mature, and old throi bocytes are distinguished. They also differ in size, shape, colour and stn ture; 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 ex-ination 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 ded to it, erythrocytes gradually settle by gravity. Then they agglomerate o heavier groups which precipitate at a faster rate. Agglomeration is amoted by some protein components of the plasma (globulins, irinogen) and by mucopolysaccharides. Therefore, the processes which ;rease their accumulation in the blood are attended by acceleration of I’throcyte sedimentation. This condition occurs in most inflammatory ocesses, infections, malignant tumours, collagenoses, nephroses, and N sue decomposition; to a certain measure, this acceleration is propor-inal 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 te is slowed (heart failure).
Erythrocyte sedimentation rate is not an independent diagnostic symp-m; it only indicates the activity of the process. It is important in this pect 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 mperature elevation and leucocytosis in appendicitis or myocardial ifr-sK ! irction; its normalization is also slower thaormalization of the men- J oned symptoms. The normal ESR does not rule out the presence of I isease which would be usually attended by an ncreased 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 invthe oviet
half of full capacity (50 divisions). The solution is blown outQito a J atch glass or into a test tube. Using the same capillary,
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
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. ilLc 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 injection needle 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.
ASSESSMENT OF HAEMOLYSIS
Evaluation of haemolysis becomes necessary mainly in anaemia of the haemolytic character. Erythrocytes undergo constant decomposition in physiological conditions (haemolysis). In pathological haemolysis, haemoglobin destruction is intensified to increase formation of unbound bilirubin and excretion of stercobilin with faeces and urine. This is an important symptom of pathological haemolysis (see “Liver and Bile Ducts”).
Another sign suggesting haemolysis is the degree of osmotic stability (resistance) of erythrocytes. Congenital microspherocytic haemolytic anaemia is characterized by decreased osmotic stability of erythrocytes. This anaemia is diagnosed by mixing blood specimens with sodium chloride solutions whose concentration increases in 0.02 per cent gradient from 0.2 to 0.7 per cent (1 ml of each solution). The mixtures are shaken and the test tubes are allowed to stand for 5-20 hours to complete sedimentation of erythrocytes (or the liquids are centrifuged after 1-hour standing). The test tubes where haemolysis takes place are separated. The minimum resistance is determined by the test tube where the concentration of sodium chloride is the highest and the pink colour becomes appreciable. The maximum resistance is determined by the test tube where the concentration of sodium chloride is the lowest and in which there is no sediment. Normally haemolysis begins at sodium chloride concentrations from 0.42 to, 0.46 per cent and terminates at 0.30 to 0.36 per cent. In haemolytic anaemia haemolysis begins at 0.54-0.70 per cent and ends at 0.40-0.44 per cent concentration of sodium chloride.
The third sign of haemolysis (also only relative) is reticulocytosis. Increased decomposition of erythrocytes stimulates erythropoiesis. The number of reticulocytes increases although the increase is not always proportional to the degree of haemolysis.
Blood in the human body is liquid because of the physiological dynamic equilibrium of the coagulation and anticoagulation systems. If the activity of any procoagulant decreases or is lost, or the activity of anticoagulants increases, there develops a tendency to haemorrhage (haemorrhagic diathesis). If the relation is reversed, the tendency develops to increasec coagulability of the blood and formation of thrombus. Bleeding ir haemorrhagic diathesis is associated with haemorrhage of fine capillaries while haemostasis is effected by a series of sequential mechanisms whicl prefect the body from profuse loss of blood.
The first event leading to haemostasis is formation of a white thrombus consisting o thrombocytes which have undergone the so-called viscous metamorphosis. This term is use to describe a series of consecutive phases in the transformation of the thrombocyte: after blood vessel is injured, thrombocytes stick to the injured site (adherence) and fuse (aggregs tion). Blood platelets stick together to lose their usual shapes and to turn into a clot that ai rests bleeding from the injured capillary or a larger vessel before a red thrombus is formec The platelets then dissolve to liberate substances promoting coagulation of blood, contractio of the vessel (serotonin), and consofrdafion of the clot. The event following formation of tfc white thrombus is activation of plasmic, tissue, and thrombocytic factors which cau.’ precipitation of fibrin threads, coagulation of blood, and formation of a red thrombus, whic is larger and stronger than the white thrombus.
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,
The blood coagulation process can be divided into three phases. The first begins at the m ment 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 particip tion of plasma factors XII, XI, X, IX, V, and three platelet factors in the presence of t
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 thf 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 blo< 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 fulfils 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 3T^C! 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
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
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
Cupping glass test. Air is evacuated from a cup applied to the skin (rarefaction of about
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 recalcificatnn. As the activity of the coagulants increases (tendency to , thrombosis) u * 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 bjood (tendency^to 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
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 thj 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 th 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 coagulograr 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 {^osteomyelosclerosis). Changes in the bone tissue are better revealed \ X-rays. The spleen is not seen during common X-ray examinatioi Splenoportography is a special technique which is used for examining tl vessels of the spleen (see section on splenoportography).
RADIOISOTOPE METHODS OF STUDY
The spleen function is studied by administering plasma or erythrocyt labelled with radioactive iron (59Fe) into the circulatory system. Foci < erythropoiesis, e.g. in erythraemia and other affections, can be establish! by this method.
The spleen can also be scanned with the patient’s erythrocytes labell by radioactive chromium (51Cr) or a colloidal solution of gold (198A which is captured by the reticuloendothelial cells. This method is suitat for determining the spleen dimensions and for revealing focal affections it.
