ACUTE MEDICAL EMERGENCIES - PART 9 doc

Remember that high mean cell haemoglo-bin concentrations do not occur in red cell disorders because the haemoglobin concen-tration is already near saturation point in normal red cells..

INTERPRETATION OF FRONTAL CHEST RADIOGRAPHS

Adequacy

Having made sure it is the correct radiograph, check the side marker and look for anydetails written or stamped on the film This will tell you if the film is posteroanterior oranteroposterior Assess the exposure, by looking at the midthoracic intervertebral discsand noting if they are just visible through the mediastinal density In overexposed filmsall the intervertebral discs are seen and the radiograph appears generally blacker In con-trast underexposure gives rise to poor definition of structures and boundaries

The film should show the lung apices and bases including the costophrenic recesses,the lateral borders of the ribs, and peripheral soft tissues The right hemidiaphragmshould reach the anterior end of the right sixth/seventh rib or the ninth/tenth rib poste-riorly on full inspiration Poor inspiration (diaphragm higher than anterior fifth rib)affects the lower zone vessels such that they are compressed and appear more prominent.This in turn leads to vague lower zone shadowing In addition, the heart appearsenlarged because the diaphragms are high and the heart lies more horizontally

Alignment

This is determined by looking at the relationship between the spinous processes of theupper thoracic vertebrae and the medial aspects of the clavicles The ends of both clavi-cles should be equidistant from the central spinous process

As with adequacy, alignment of the patient to the X-ray can significantly alter the sizeand shape of the chest contents on the radiograph For example, if the patient is rotatedthere is distortion of the mediastinal contours as well as inequality in the transradiancy

of the hemithoraces

In addition to postural and rotational artefacts, remember the configuration of thepatient’s chest wall can also give rise to abnormal appearances For example, pectusexcavatum can alter the size, shape, and position of the mediastinum, as well as produc-ing inequality in the transradiancy of the lungs

Bones

The posterior, lateral, and anterior aspects of each rib must be examined in detail Thiscan be done by tracing out the upper and lower borders of the ribs from the posteriorcostochondral joint to where they join the anterior costal cartilage at the midclavicularline The internal trabecula pattern can then be assessed

Finish assessing the bones by inspecting the visible vertebrae, the clavicles, scapulaeand proximal humeri However, for full assessment specific views must be obtained

Cartilage and joints

Calcification in the costal cartilage is common in the elderly – similarly in the larynx.Occasionally the glenohumeral joints are seen on the chest X-ray They may show eitherdegenerative or inflammatory changes

The mediastinum normally occupies the centre of the chest radiograph and has a welldefined margin.You should consider the upper, middle (hila), and lower (heart) parts ofthe mediastinum

Upper mediastinum

Check the position of the trachea This should be central

The upper left mediastinal shadow is formed by the left subclavian artery Thisnormally gives rise to a curved border which fades out where the vessels enter the neck.The left outer wall of the trachea is not visible in this area because the subclavian vesselsseparate the trachea from the aerated lung Inferiorly, the left paratracheal region is inter-rupted by both the aortic knuckle and the main pulmonary artery with the spacebetween the two being known as the ‘aortopulmonary window’ The aortic knuckleshould be well defined

Middle mediastinum

The hila shadows are produced mainly by the pulmonary arteries and veins The majorbronchi can be identified as air containing structures but the bronchial walls are com-monly only visible when seen end on Though a contribution is made to these shadows

by the hilar lymph nodes, they cannot be identified separately from the vascular shadows.The left hilum is usually higher than the right

Any lobulation of the hilar shadow, local expansion or increase in density comparedwith the opposite side indicates a central mass lesion Central enlargement of the pul-monary arteries may mimic mass lesions but the vascular enlargement is usually bilat-eral, accompanied by cardiomegaly and forms a branching shadow

Lower mediastinum

The overall position, size, and shape of the heart should be noted first Normally the diac shadow can have a transverse diameter which is up to 50% of the transverse diame-ter of the chest on a posteroanterior film Cardiomyopathy or pericardial effusion canboth give rise to a globular heart shadow but further diagnostic clues are usually avail-able from the clinical history and examination

car-The heart borders can then be assessed car-The heart silhouette should be sharp andsingle with loss of a clear border indicating neighbouring lung pathology A double out-line suggests a pneumomediastinum/pneumopericardium With a pneumomediastinum

a translucent line can usually be seen to extend up into the neck and be accompanied bysubcutaneous emphysema

Inspection of the heart is completed by checking for calcification (valves and cardium) and retrocardiac abnormalities, e.g hiatus herniae, increased density or thepresence of foreign bodies

peri-Lungs and diaphragm

Lungs

These are best assessed initially by standing back from the radiograph so that you cancompare the overall size and transradiancy of both hemithoraces A number of changesmay be seen

Reduced volume The commonest cause of lung volume loss is lobar collapse Whencomplete, these give rise to dense white shadows in specific locations and are usuallyaccompanied by hilar displacement, increased radiolucency in the remaining lobes and

reduction in the vascular pattern due to compensatory emphysema.When the collapse isincomplete, consolidation in the remaining part of the lobe is evident.

Reduced density The transradiancy of both lungs should be equal and their outer edgesshould extend out to the ribs laterally and the diaphragm below Any separation indicatesthat there is a pneumothorax.Within the normal lungs the only identifiable structures areblood vessels, end on bronchi and the interlobar fissures Air trapping gives rise toincreased translucency and flattening of the dome of the diaphragm In extreme cases themediastinum may be displaced to the contralateral side

Increased density There are several causes for an increase in pulmonary density In solidation the density is restricted to either part or all of a pulmonary lobe as a result ofthe air being replaced with fluid With segmental consolidation the density is roundedand the edges blurred When the whole of the lobe is involved the interface with neigh-bouring soft tissues is lost This can lead to alteration in the outline of the heart anddiaphragm depending upon the location of the lobe (see earlier)

con-Pleural fluid is seen initially as blunting of the costophrenic angle As more lates the fluid level is easier to make out However, if the patient is supine the fluid col-lects posteriorly and gives rise to a general ground-glass appearance on the affected side.Consequently, an effusion may be missed until it is large or the frontal and erect chestradiograph is carried out

accumu-Pulmonary oedema presents as generalised fluffy air space shadowing which can beaccompanied by Kerley B lines due to interstitial lymphatic congestion

The position, configuration, and thickness of the fissures should also be checked – thing more than a hairline thickness should be considered abnormal To visualise a fis-sure the X-ray beam needs to be tangential; therefore, only the horizontal fissure isevident on the frontal film, and then only in 50% of the population It runs from the righthilium to the sixth rib in the axilla The azygos fissure is seen in approximately 1% of thepopulation The oblique fissures are only identified on the lateral view

any-Diaphragm

The diaphragm must be checked for position, shape, and clarity of the cardiophrenic andcostophrenic angles The outline of the diaphragm is normally smoothly arcuate with thehighest point medial to the midline of the hemithorax Lateral peaking, particularly onthe right, suggests a subpulmonary effusion or a haemothorax in the appropriate clinicalsetting

In the vast majority of patients the right diaphragm is higher than the left However,elevation of either side can result from pathology in the abdomen or damage to thephrenic nerve In this situation the patient’s history will be very helpful in distinguishingbetween these possible causes

The upper surface of the diaphragm is normally clearly outlined by air in the lungexcept where it is in contact with the heart and pericardial fat Loss of clarity may indi-cate collapse or consolidation of the lower lobe It could also indicate diaphragmaticrupture

Extrathoracic soft tissue

Start at the top with the neck and supraclavicular area, and continue down the lateralwall of the chest on each side Note any foreign bodies and subcutaneous emphysema.The latter is often seen in the cervical region and appears as linear transradiancies alongtissue planes When gross it may interfere with the assessment of the underlying lung

Presence and position of any medical equipment

The position and presence of any invasive medical equipment must be assessed while theradiograph is examined so that potential complications can be identified A further chestX-ray should be performed after the placement of any of these devices in order toexclude or detect the above complications

Reassess commonly missed areas

Once the system described above has been completed, it is important to reevaluate thoseareas where pathology is often overlooked These include:

● the lung apices

● behind the heart shadow

● under the diaphragm

● peripheral soft tissues

Summary of the system for assessing frontal chest radiographs

● Assess the adequacy of the film

Patient’s personal details Projection of the X-ray beam Exposure of the film

Area of the chest on the film Degree of inspiration

● Assess the alignment of the film

● Assess the bones

Extrathoracic Spine

Shoulder Foreign bodies Air

Under the diaphragm

● Assess the cartilage and joints

● Assess the soft tissue

Mediastinum Upper

Middle (hila) Lower (heart) Lungs and diaphragm Lungs

Size Density Fissures Nodules and opacifications Diaphragm

Position Shape Clarity of the angles Foreign bodies Air

Under the diaphragm

● Reassess commonly missed areas of the film

Apices Behind the heart Under the diaphragm Peripheral soft tissues

25

Haematological investigations

OBJECTIVES

After reading this chapter you will be able to:

● identify which haematological tests are useful in the acute medical patient

● describe the rational use of such tests

● use test results to aid further clinical management

INTRODUCTION

A full blood count is probably the commonest laboratory investigation that is requestedbecause it is a “routine test” There is, however, no such commodity as a routine test andyou should be able to justify requesting any investigation A similar situation, thoughmuch less common, exists when requesting assessment of the components of the clottingcascade It is, therefore, important that you critically appraise your requests and alsointerpret all the available information provided by, for example, a full blood count, andnot just the haemoglobin, as often occurs

RULES

When interpreting haematological results:

● Always request investigations and interpret results in light of clinical findings

● Beware:

– the isolated abnormality– bizarre results

– results that do not fit with the clinical picture

● If in doubt repeat the test

● Always seek corroborative evidence from:

– clinical findings– other test results

● Always observe serial results for trends

Reading: 30 minutes

Many haematological disorders are identified by, or suggested by, an abnormality in thefull blood count The result usually relates to three major cell lines in peripheral blood:erythrocytes, leucocytes, and platelets In addition there is a wealth of numerical infor-mation describing these cell lines that is often ignored – at the clinician’s peril.This infor-mation, generated by automatic haematology counters, should be used to the clinician’sadvantage – hence the need for revision of some of the key cell count components

HAEMOGLOBIN LEVEL

The normal levels of haemoglobin are 15 ± 2 g/dl (150 ± 20 g/l) for men and 14 ± 2 g/dl(140 ± 20 g/l) for women In the acute medical patient a raised haemoglobin often indi-cates polycythaemia.This is commonly associated with chronic respiratory disease ratherthan the rare polycythaemia rubra vera In contrast, the haemoglobin level may be lowindicating anaemia However, remember that in patients with acute blood loss thehaemoglobin level may be normal initially, until either compensatory measures fail orhaemodilution occurs

The red cell count is quoted by some laboratories, but this has little diagnostic value

in the acute medical patient However, the combination of haemoglobin and red cellcount can be used to derive the mean cell haemoglobin (MCH).This gives a reliable indi-cation of the amount of haemoglobin per red cell and is measured in picograms (normalrange 29.5 ± 2·5 pg).The mean cell haemoglobin concentration (MCHC) represents theconcentration of haemoglobin in grams per decilitre (100 ml) of erythrocytes (normalrange 33 ± 1·5 g/dl) This is obtained by dividing the haemoglobin concentration by thepacked cell volume A low mean cell haemoglobin concentration is due to a low haemo-globin content in the red cell mass and indicates deficient haemoglobin synthesis Thusthe red cells will appear pale (hypochromic) Remember that high mean cell haemoglo-bin concentrations do not occur in red cell disorders because the haemoglobin concen-tration is already near saturation point in normal red cells The mean cell haemoglobinconcentration, unlike the mean cell haemoglobin, assesses the degree of haemoglobini-sation of the red cells irrespective of their size and is useful in assessing the extent ofunder-haemoglobinisation The packed cell volume (PCV or haematocrit) represents aproportion (by volume) of whole blood occupied by the red cells and is expressed as apercentage (normal range for men 47 ± 7, women 42 ± 5%) The packed cell volume orhaematocrit is always elevated in polycythaemia irrespective of cause However, this mayonly be relative when haemoconcentration occurs as a result of fluid loss producing adecrease in plasma volume The packed cell volume is therefore reduced in the presence

of excess extracellular fluid and raised in fluid depletion The mean cell value (MCV)measured in femtolitres (normal range 85 ± 10 fl) indicates erythrocyte size Thus, it isincreased in patients with macrocytic disorders (e.g vitamin B12/folate deficiency) andreduced in the presence of microcytes (e.g iron deficiency anaemia)

It is important to realise that red cell indices indicate the average size and degree ofhaemoglobinisation of red cells They are, therefore, only of value if combined with ablood film examination that will augment the information about the relative uniformity

of changes in either cell size or haemoglobin concentration

THE BLOOD FILM

The benefits of the blood film have already been described Some of the common terms

RED CELL ABNORMALITIES

Red cell abnormalities can be classified as alterations in either number or morphology

Alteration in number

An increase in red cells is described as polycythaemia (see earlier) In contrast anaemia

is described as diminished oxygen carrying capacity of the blood due to either a tion in the number of red cells or in the content of haemoglobin or both.This may be due

reduc-to deficient red cell production and/or excessive loss Although there is some overlapbetween these conditions this classification does provide a convenient way of consideringthis condition (see the next box)

Deficient red cell production

Iron deficiency anaemia secondary to:

● poor dietary intake

● invasion of bone marrow by, e.g leukaemia, Hodgkin’s lymphoma, myeloma

● toxic effects on erythroblasts, e.g uraemia, chronic infections, and malignant disease

Morphological terms on blood cell reports

Red cells Pale cells Hypochromia indicating defective

haemoglobinisation or haemoglobin synthesis Macrocytes Large cells, abnormal red cell production,

premature release, megaloblastic erythropoiesis, haemolysis Anisocytes Variation in cell size Poikilocytes Variation in cell shape

Schistocytes Burr cells Fragmented forms, usually indicate red cell trauma Sickle cells Sickling disorders

White cells Hypersegmented Usually indicates vitamin B12 or folate

neutrophils deficiency Left shift neutrophils Indicate that neutrophils are being prematurely

released Toxic granulation Increased neutrophils

Cytoplasmic granularity Usually associated with underlying infection Atypical lymphocytes Likely viral infection

Blast cells Usually indicate leukaemia Platelets Clumping Often causing an artificially low platelet count

An anaemia with a coexistent reduction in both white cells and platelets is referred to

as pancytopenia

Alteration in morphology

An anaemia with reduced mean cell volume, mean cell haemoglobin, and mean cellhaemoglobin concentration, i.e microcytic hypochromic anaemia, is highly suggestive ofiron deficiency Therefore a serum ferritin should be requested before treatment withiron is started However, if there is coexistent thrombocytosis then this type of anaemiacould indicate ongoing blood loss or inflammation If none of these conditions are evi-dent then it is possible that the microcytic hypochromic picture is a manifestation ofthalassaemia, which is rare in the United Kingdom In contrast an anaemia with raisedmean cell volume and mean cell haemoglobin is suggestive of a variety of conditionsincluding a deficiency in vitamin B12 and/or folic acid, hypothyroidism, and alcohol use

An anaemia with normal mean cell volume, mean cell haemoglobin and mean cellhaemoglobin concentration, i.e a normochromic normocytic anaemia, can reflectchronic disease (e.g inflammation, myeloma), acute blood loss or haemolysis

Haemolysis is usually associated with a normochromic normocytic anaemia althoughsome of the red cells can be large due to the release of a large number of immature redcells, i.e reticulocytes The latter can also occur following haemorrhage or in response totreatment with iron, folic acid, and vitamin B12.The comment polychromasia (grey/bluetint to cells) is often recorded on the full blood count indicating a reticulocyte response

A formal count of these cells can also be done

Haemolytic anaemia is a term that describes a group of anaemias of differing cause,which are all characterised by abnormal destruction of red cells The questions asked toidentify the cause of haemolysis are shown in the box

These questions can be used to produce a “user frendly” classification of haemolyticanaemia as shown in the box

Three key questions in the diagnosis of haemolytic anaemia

● Is it an inherited or acquired disorder?

● Is the location of the abnormality within the red cells (intrinsic) or outside (extrinsic)?

● Are the red cells prematurely destroyed in the blood stream (intravascular) or outside in the spleen and liver (extravascular)?

Excessive loss of red blood cells

● Haemorrhage

● Abnormal haemolysis

● Hypersplenism

● Drugs

LABORATORY DIAGNOSIS OF HAEMOLYTIC ANAEMIA

The most likely clue is a normochromic normocytic anaemia with prominent cytes Other laboratory results include:

reticulo-● unconjugated hyperbilirubinanaemia (thus a lack of bilirubin in the urine)

● low haptoglobin (a glycoprotein that binds to free haemoglobin and is thus depleted

in haemolysis)

● Haemoglobin and haemosiderin can be detected in the urine with intravascularhaemolysis

Inherited disorders

More specific tests will be requested after taking a comprehensive history as this is likely

to provide clues to underlying inherited disorders The presence of hereditary tosis or elliptocytosis will be seen on the blood film

spherocy-The thalassaemias are a heterogeneous group of disorders affecting haemoglobin thesis; they will be diagnosed from the medical history, clinical examination, blood film,and haemoglobin electrophoresis to identify structural haemoglobin variants In addi-tion, the presence of sickle cell syndromes will be diagnosed from the clinical history, inparticular that of the family, and the presentation with haemolysis, vascular occlusivecrises, and sequestration crises Under these circumstances the blood film is likely toshow the presence of sickle shaped cells Haemoglobin electrophoresis may reveal anabnormal haemoglobin such as Hbss in sickle cell anaemia with no detectable haemo-globin A

syn-The two common abnormalities of red cell metabolism resulting in haemolysis are cose 6 phosphate dehydrogenase deficiency and pyruvate kinase deficiency As well as thefeatures of intravascular haemolysis described earlier, specific enzyme levels can also bemeasured to produce a definitive diagnosis

glu-Acquired disorders

Autoimmune haemolytic anaemia is a form of acquired haemolysis with a defect outsidethe red cell The bone marrow produces structurally normal red cells These are prema-turely destroyed by the production of an aberrant antibody targeted against one or moreantigens on the red cell membrane Once the autoantibody has bound with the antigen

Classification of haemolytic anaemias

● Inherited disorders Red cell membrane hereditary spherocytosis

hereditary elliptocytosis Haemoglobin thalassaemia syndromes

sickle cell disorders Metabolic pathways glucose 6 phosphate dehydrogenase deficiency

pyruvate kinase deficiency

● Acquired disorders Immune warm and cold autoimmune haemolytic anaemia Isoimmune rhesus or ABO incompatibility

Non-immune and trauma valve prosthesis, microangiopathy, drugs,

infection, chemicals, hypersplenism

on the red cell the exact type of haemolysis is determined by the class of antibody as well

as the surface antigen A simple classification of these conditions is either warm and colddepending on whether the antibody reacts better with red cells at 37ºC or 4ºC respec-tively

Warm autoimmune haemolytic anaemia

This is the commonest form of haemolytic anaemia The erythrocytes are coated witheither IgG alone or IgG and complement or complement alone Premature destruction

of red cells usually occurs in the liver and spleen The most characteristic laboratoryabnormality in warm autoimmune haemolytic anaemia is a positive direct antiglobulintest (DAT or Coombs test) As a reminder the DAT is where red cells are already sensi-tised and have immunoglobulin bound to their surface antigens Addition of extrinsicantihuman globulin results in haemolysis, i.e a positive direct Coombs test In contrast,

the indirect test is where normal red cells have to be sensitised in vitro by the addition

of the test serum containing red cell antibodies Finally antihuman globulin is added.Agglutination indicates the presence of red cell antibodies, as used in red cell typing

Cold autoimmune haemolytic anaemia

This is generally associated with an IgM antibody Isoimmune haemolytic anaemia mayoccur with rhesus or ABO incompatibility, and in the context of adult medicine this mayfollow a blood transfusion reaction

Non-immune and traumatic autoimmune haemolytic anaemia is most frequentlymanifested by a microangiopathic picture This is one of the most frequent causes ofhaemolysis and describes intravascular destruction of red cells in the presence of anabnormal microcirculation Causes of microangiopathic haemolytic anaemia are listed inthe box

Classification of autoimmune haemolytic anaemia

● Warm (usually IgG mediated) Primary

idiopathic Secondary lymphoproliferative disorders other neoplasms

drugs infections connective tissue disorders

● Cold (usually IgM mediated) Primary

cold haemagglutinin disease Secondary

lymphoprolific disorders infections, e.g mycoplasma paroxysmal nocturnal haemoglobinuria cold haemoglobinuria

TOTAL AND DIFFERENTIAL LEUCOCYTE COUNT

The total white count varies markedly as there is a diurnal rhythm with minimal countsoccurring in the morning This may rise during the rest of the day or following stress,eating or during the menstrual cycle The total leucocyte count is 7 ± 3 × 109

/l Thiscomprises:

Malignancy Drugs Reduced numbers Drugs (production failure) Chemicals

Severe infection Marrow infiltration by malignant tumour or marrow fibrosis Specific deficiencies of vitamin B12 and folic acid

Idiopathic Peripheral sequestration/hypersplenism

Shock Severe infection

Causes of microangiopathic haemolytic anaemia

● Disseminated intravascular coagulation (DIC)

* In suspected viral infections a blood film may show changes in lymphocyte numbers and morphology.

Basophils rarely have any significance in the acute medical setting

THE PLATELET COUNT

There is a marked variation in the normal platelet count ranging from 150 to 400 × 109

/l.Common platelet disorders are listed in the next box

Disorders of eosinophils

Raised numbers Parasitic infections

Atopy including asthma and drugs insensitivity

Chronic eczema Malignant tumours, e.g Hodgkin’s disease

Disorders of monocytes

Raised numbers Infective endocarditis

Typhus fever Malaria Kala-azar Systemic lupus erythematosus Certain clinical poisonings, e.g trichloroethylene

Disorders of lymphocytes

Raised numbers (lymphocytosis, Viral infection, especially glandular fever*

i.e > 4 × 10 9 /l) Chronic lymphatic leukaemia

Typhoid fever Brucellosis Reduced numbers (lymphopenia) Corticosteroids

Viral infections*

Cytotoxic drugs Ionising radiation

Thrombocytopenia is a common finding The risk of spontaneous haemorrhage isunusual unless the platelet count falls below 20 × 109

/l

COAGULATION

The physiological pathway of blood coagulation is an interlinked cascade of factorswhich most doctors learn for examinations The basic principles are three activationpathways: intrinsic, extrinsic, and alternative, which have a final common pathway.Individual components of these pathways are shown in Figures 25.1 and 25.2

Figure 25.1 Clotting pathways

Disorders of platelets

Raised number (thrombocytosis) Inflammation, e.g Crohn’s disease

Haemorrhage Essential thrombocytosis (rare) Polycythaemia rubra vera (rare) Reduced number (thrombocytopenia) Deficient production, e.g hypoplasia replacement

with leukaemic cells or fibrosis Dyshaemopoiesis secondary to vitamin B12 deficiency

Increased destruction of platelets, e.g drugs or autoimmune

Sequestrated in the spleen Increased consumption (disseminated intravascular coagulation)

Blood clotting is a vital defence mechanism that is regulated to ensure adequate andappropriate activation.

The major inhibitors of coagulation circulating in the plasma are:

● Antithrombin III This is the most potent inhibitor of the terminal proteins of thecascade, particularly factor X and thrombin Its activity is greatly increased by inter-action with heparin

● Protein C is a vitamin K dependent plasma protein which inactivates cofactors Vaand VIIIa as well as stimulating fibrinolysis Protein C is converted to an activeenzyme from interaction with thrombin Protein S is a cofactor for protein C

● Fibrinolytic systems.This is the endogenous system for fibrin digestion and is shown

in Figure 25.2 Fibrin clots are broken down by plasmin that is produced from

plas-minogen by “activator enzymes” Plasmin also inhibits thrombin generation, thusreacting as an anticoagulant In addition, fibrin degradation products have a similareffect Fibrinolysis is also under strict control Circulating plasmin is inactivated bythe protease inhibitor α2 antiplasmin.

Tests for the assessment of coagulation

In most acute medical situations, an assessment of the coagulation cascade only requires:

● prothrombin time – a measure of the function of the extrinsic pathway

● activated partial thromboplastin time – assesses the intrinsic pathway

● assessments of fibrinolysis, e.g fibrinogen level, fibrin degradation product level orD-dimer quantitation – are often used as markers of disseminated intravascular coag-ulation

The common causes of prolonged prothrombin and activated partial thromboplastintimes are listed in the box

SUMMARY

A limited number of haematological investigations are required in the acutely ill medicalpatient Much of the information available is often underused; therefore a thoroughunderstanding of the morphology and normal values of, in particular, red cells isextremely useful A blood film is an underused investigation that can yield significantrelevant information in the acute medical setting These initial investigations, combinedwith a phased history, will influence the selection of subsequent haematological tests

Common causes of prolonged prothrombin and activated partial thromboplastin times Prothrombin times Activated partial thromboplastin times

Warfarin Heparin

Vitamin K deficiency von Willebrand’s disease Disseminated intravascular coagulation Liver disease

Lupus anticoagulant syndrome

26

Biochemical investigations

OBJECTIVES

After reading this chapter you will be able to:

● understand the importance of interpreting urea, electrolyte, and creatinine results inlight of clinical findings

● systematically assess urea, electrolyte, and creatinine results

● use these results to aid your clinical management

INTRODUCTION

Urea, electrolytes, and creatinine are commonly requested laboratory investigations Alltoo often there is little thought about why these investigations have been requested andwhat the abnormalities, in particular of the electrolytes, may indicate This chapter willprovide a systematic approach to the assessment of such investigations, but before this isdescribed there are certain rules which have to be obeyed

RULES FOR THE INTERPRETATION OF UREA, ELECTROLYTES AND CREATININE

● Always interpret the results in the light of clinical findings

● Beware – the isolated abnormality

– bizarre results– results that do not fit the clinical picture

● If in doubt, repeat the test

● Always seek corroborative evidence from – clinical findings

– other test results

● Always observe serial results for trends

Reading: 15 minutes

GUIDELINES FOR INTERPRETATION OF UREA,

ELECTROLYTES AND CREATININE

A review of essential facts

Urea

Blood urea provides an assessment of glomerular function However, it can be influenced

by many exogenous factors including food intake, fluid balance, gastrointestinal orrhage, drugs, and liver function Normal plasma urea is 4·6–6·0 mmol/l

haem-Creatinine

This provides a better indication of renal function Plasma creatinine levels are tional to muscle mass Creatinine gives a reasonable indication of changes in glomerularfiltration providing the body weight remains stable Normal plasma creatinine is60–125 micromol/l

propor-Potassium

This is the most important intracellular cation and only approximately 2% of the totalbody potassium is found in the extracellular fluid Normal plasma potassium is3·5–5·0 mmol/l

Bicarbonate

Bicarbonate is an important anion Normal plasma bicarbonate is 24–28 mmol/l In avenous blood sample the bicarbonate provides a useful, but crude, indication of theacid–base status

A systematic approach comprises:

1 assessment of the patient’s urea and creatinine

2 the relationship between the urea and creatinine

3 assessment of potassium, bicarbonate, and sodium

All results will fall into one of these five broad categories and each will be examined.

Urea raised and creatinine raised

The most common diagnosis would be renal failure Therefore confirmatory evidenceshould be sought

● Check plasma potassium – this will remain normal until the glomerular rate hasfallen below 10 ml/min Hyperkalaemia is common, but can be secondary to a meta-bolic acidosis, catabolism or haemolysis

● Check bicarbonate – this is often reduced reflecting the acidosis associated withuraemia or a failure of bicarbonate secretion

● Check serum sodium – this may be normal but is often low due to overhydration anddilution.To provide further information, plasma osmolality along with urine, sodium,osmolality, and urea should be measured to distinguish between acute and estab-lished renal failure

Urea low and creatinine low

This commonly results from fluid overload

● Check potassium, bicarbonate and sodium Low values would be expected

The basic problem is that sodium is retained but to a significantly lesser extent thanthe degree of water retention This commonly results from two mechanisms

● Increased water intake, e.g excess intravenous fluids, excess drinking (both logical and psychological polydipsia) and water absorption during bladder irrigation

patho-● Inability to excrete water, e.g SIADH, adrenocortical insufficiency, hypothyroidism,and drugs that reduce renal diluting capacity, e.g diuretics Under these circum-stances there is water retention but body sodium is normal with possibly only smallincrease in extracellular fluid volume which will be undetected clinically In contrast

if both extracellular fluid sodium and water are increased, but more water is retainedthan sodium, hyponatraemia will result with expansion of the extracellular fluid vol-ume producing oedema Note that the discriminating factor between these condi-tions is based on the clinical presence of oedema

The first group of conditions with water retention and a normal serum sodium is oftenreferred to as hyponatraemia with clinically normal extracellular fluid volume In con-trast hyponatraemia with expansion of the extracellular volume occurs with cardiac,renal, and liver failure The urine sodium can provide further clues, in particular, in the

Diagnosis

↑ ↑ Urea ↑ ↑ Creatinine Renal failure

↓ Urea ↓ Creatinine Fluid overload Urea < creatinine Low protein diet

Liver failure Dialysis Urea > creatinine Fluid depletion, e.g dehydration, fever, trauma

Drugs, e.g diuretics Elevated protein, e.g diet, gastrointestinal bleed, catabolism

Urea normal Creatinine normal Check for any electrolyte abnormality

patient who is hyponatraemic with an increased extracellular volume where the urinesodium is usually less than 10 mmol/l (except in renal failure).

An interesting variant is beer drinker’s hyponatraemia Beer has a low sodium content

If in excess of five litres is consumed daily then hyponatraemia may result, usually with aclinically normal extracellular volume

Urea less than creatinine

Low urea in relation to the creatinine usually indicates low protein diet or rarely liver ure or post dialysis Low urea in liver disease is usually attributed to reduced synthesis

fail-● Check potassium

– normal with low protein diet and post dialysis– normal in liver disease unless diuretics are used– low in liver disease with diuretic use

Urea greater than creatinine

These results suggest fluid depletion, e.g associated with dehydration, fever, infection ortrauma Drugs, in particular diuretics, can induce a similar problem An alternativeexplanation is increased protein which may be from a dietary source, following a gastro-intestinal haemorrhage, or secondary to catabolism

reflect-The major cause is excessive sodium loss which is usually:

● from the gastrointestinal tract secondary to vomiting, diarrhoea, fistulae or intestinalobstruction

● from the kidney, for example, during the diuretic phase of acute tubular necrosis

● due to excess diuretic therapy (including mannitol or the osmotic effect of caemia)

hypogly-● due to postobstructive diuresis

● due to adrenocortical insufficiency or severe alkalosis where increased urinary loss ofbicarbonate necessitates an accompanying cation, usually sodium

In addition, salt may be lost:

● from the skin in severe sweating, burns or erythroderma

● in association with inflammation of the peritoneum or pancreas

● following the removal of serous effusions, for example, ascites

The key feature to remember is that salt loss is always associated with loss of water andother ions, in particular, potassium However, it is often easy to underestimate the loss ofsalt if another solute such as glucose is present in excess, i.e hyperglycaemia This willtend to retain fluid within the extracellular fluid and the severity of the situation will beonly unmasked when the hyperglycaemia is treated The urine sodium again will provide

a good indicator in that it will be less than 10 mmol/l in all conditions, unless there is an

Urea normal and creatinine normal

Therefore exclude any electrolyte abnormality

● Check potassium – high; secondary to haemolysis, increased intake (usually genic) or redistribution, e.g with acidosis or muscle injury

iatro-Under these situations the serum sodium is normal Hyperkalaemia may also be sent because of reduced excretion, for example, with acute renal failure or the use ofpotassium sparing diuretics Again the sodium is usually normal although it can bereduced in the former because of dilution

pre-An elevated potassium in the presence of reduced sodium is suggestive of adrenalinsufficiency

● Check potassium – if low the commonest cause is a metabolic alkalosis; thereforecheck the bicarbonate level

Potassium may be lost from the gastrointestinal tract, for example, with diarrhoea ormalabsorption Under these circumstances the serum sodium is usually normal In con-trast, renal loss, associated with either diuretic therapy or cardiac or liver failure, isaccompanied by hyponatraemia A normal urea and creatinine with low potassium andhigh sodium combined means that excess of glucocorticoid and mineral corticoid hor-mones has to be excluded

● Check bicarbonate – high, when associated with metabolic alkalosis and kalaemia

hypo-● Check sodium – hyponatraemia in the context of normal urea, creatinine, and sium is related to the extracellular fluid volume (see earlier)

potas-Pseudohyponatraemia is a trap for the unwary Sodium is present only in the aqueousphase of plasma If there is an associated abnormal amount of lipid the water volume will

be reduced and the measured sodium will be low This result will be spurious because ofthe high proportion of lipid In nephrotic syndrome or diabetes mellitus, for example,one litre of plasma may comprise 600 ml of water and 400 ml of lipid with a measuredsodium of 120 mmol/l The true calculated value of sodium, however, when expressedaccording to the volume of water, is 120 mmol/l of sodium in 600 ml of water –

200 mmol/l Although this is an extreme example, it indicates that if such problems arenot identified inappropriate treatment may occur A way to clarify this situation is tomeasure urine sodium and chloride which are low in true hyponatraemia

SUMMARY

These guidelines must be interpreted in the light of clinical findings They will, however,facilitate the diagnosis of common conditions