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Lobar pneumonia with jaundice in adult Nigerians
206 TRANSACTIONS OF THE ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE.
Vol. 57. No. 3.
May, 1963.
LOBAR PNEUMONIA
WITH JAUNDICE IN ADULT
NIGERIANS
BY
*ELIZABETH W. HALL, M.B. AND **E. H. O. PARRY, M.R., M.R.C.P.t
(From the Departments of Pathology and Medicine, University College Hospital, Ibadan, Nigeria.) It has been known for a long time that jaundice may complicate lobar pneumonia, and many reports have appeared since GARVIN (1836) wrote on " Pneumonia Biliosa." TROWELL (1960) suggested that the African with pneumonia may be particularly liable to become jaundiced. ZIMMERMANand THOMAS (1950) reviewed the earlier descriptions and concluded from these, and from 13 patients whom they studied, that the jaundice was hepatocellular in origin. T h e present study was done to investigate the jaundice further, and particularly to study changes in hepatic histology during the acute chest infection, previous studies having been limited to postmortem material. THE PATIENTS STUDIED AND THE METHODS USED
Eleven Nigerian patients admitted to University College Hospital, Ibadan, were studied. The criteria used for inclusion in this series were the signs of clinical jaundice and of classical lobar pneumonia, confirmed by radiograph of the chest. Ten patients were men ; there was one woman. Standard laboratory methods were used for serum and urine biochemical tests. Pereutaneous needle biopsy of the liver, using the Terry modification of the Gillman needle, was done from the epigastric approach to avoid infected lung and pleura. Parenteral vitamin K1 was given for 3 days before the biopsy, which was uneomplicated in every patient. The biopsies were done during the first week in all patients and serially during recovery in Case 9. All the biopsy specimens were fixed in 10 per cent. formol saline and stained by haematoxylin and eosin, silver stains for reticulin, Van Gieson, periodic aeid Schiff, phosphotungstic acid haematoxylin (PTAH) and Mallory's triehrome stain. CLINICAL FEATURES
Symptoms and Signs T h e patients had had chest symptoms for between 3 and 7 days. T w o said that their illness began with cough and jaundice. T h e r e were physical signs of lobar pneumonia in all patients and their temperatures were between 101 and 104.8°F. Seven patients had right lower lobe pneumonia, sometimes with infection in the right middle lobe also, or with signs at the base of the left lung. T w o had left lower lobe pneumonia, one left upper lobe pneumonia, and one right upper lobe pneumonia. T h e liver was enlarged in every patient and was tender in eight (Table I). * Seconded from the Royal Free Hospital School of Medicine. **Seconded from the Hammersmith Hospital and Postgraduate Medical School. t We are indebted to the physicians of University College Hospital, Ibadan, for permission to study patients under their care, to Professors K. R. Hill and G. M. Edington for reading the manuscript, and to Mr. F. E. Speed of the Medical Illustration Unit, University College Hospital, Ibadan, for the photographs.
ELIZABETH W .
TABLE I. Case
207
H A L L AND E. H. O. PARRY
Clinical features. Site
Temp.(°F.)
* Liver
Response to penicillin
Age years
Sex
15
M
R.L.L.
104.8
Good
42
M
L.U.L.
102
Good
65
M
R.L.L.
101
Good
50
M
R.L.L.
101
3T
Died
50
M
R.L.L.
103
3T
Good
38
M
R.U.L.
101
8T
Died
34
M
R.L.L.
103
3T
Poor I
31
M
R.L.L.
103
3T
27
F
L.L.L.
104
6T
Good
10
25
M
L.L.L.
104
6T
Good
11
40
M
R.L.L.
102
6T
Good
Good
* Figures represent size in liver in cm. below costal margin. (T = tender).
Course of the Disease Two of the patients died ; at necropsy one (Case 4) was found to have a consolidated right lung. The other (Case 6) had a consolidated right lung in which several small abscesses had formed. Eight of the survivors did very well when treated with penicillin only ; one only needed tetracycline because his pneumonia was slow to resolve. In the survivors, the jaundice faded quickly and the liver was usually no longer tender after the first week in hospital, although it was palpable in some patients for as long as 4 weeks after the acute illness was over. LABORATORY RESULTS (TABLE II)
Laboratory Remits (Table II) Culture of the sputum was not helpful : some patients could not produce sputum and others had had an injection of an antibiotic before admission. Although the pneumococcus was not cultured, Gram-positive diplococci were seen when the sputum was examined by Gram's stain in five patients. The serum bilirubin was high at first in all, and quickly fell to normal levels (Fig. I). The high total bilirubin was solely due to a high conjugated fraction in every patient except two (Cases 9 and 11). In six patients in whom the serum proteins were estimated on admission and after recovery, the serum albumin was low at first and invariably rose later. In Case 11 the serum glutamic oxaloacetic transaminase was consistently high during the first week (83 units, 69 units, 53 units/ml.), but the serum glutamic pyruvic transaminase was within normal limits (15 units, 21 units, 26 units/ml.). The direct Coombs' test was
208
LOBAR
PNEUMONIA
WITH
JAUNDICE
IN
NIGERIANS
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ELIZABETH W. HALL AND E. H. O. PARRY
209
18".
" • 16-
I
0 "~ 14FIG I. The total serum bilirubin during the course of lobar pneumonia.
12I0-
42-
I
7
14
21
DAYS
positive in only one of eight patients so tested. This patient, however, had a positive test only during the first week, and was found to have a non-specific cold antibody, and a warm antibody, apparently auto-immune and probably C -- C w. A red cell survival study using Cr51 was done during this patient's second week in hospital and gave an uncorrected half life of 27 days (Normal 24-34 days). The urine commonly contained bile, urobilinogen, and protein. Thick films of blood were not stained routinely for malaria parasites ; however, in no case were parasites seen in a thin film stained by Leishman's method. H I S T O L O G Y OF T H E L I V E R
1) Liver biopsy In every case the liver was abnormal. There were three consistent findings : first, cloudy swelling of parenchymal cells ; second, patchy areas of pleomorphic liver cells and nuclei ; and third, infiltration of portal tracts by inflammatory cells with occasional loci of inflammatory cells in the parenchyma. Cloudy swelling in some cases was wide spread, but more often it tended to be focal, while the remaining cells were pleomorphic. The pleomorphic liver cells occasionally showed double nuclei and more often hyperchromatic nuclei, suggesting regeneration of cells. Foci of degenerate or necrotic cells, often centrilobular, were seen in Cases 3, 4, 6, and 7 (Plate 1). The portal tracts in every cases were infiltrated by cells, usually lymphocytes, with occasional plasma cells and polymorphs (Plate 2). Although the portal tracts of livers studied at Ibadan often show excessive leucocytes, our material has shown even
210
LOBAR PNEUMONIA
WITH
JAUNDICE IN NIGERIANS
more cells than usual. In each biopsy the sinuses contained leucocytes comparable to the peripheral blood count. Foci of lymphocytes and histiocytes in the parenchyma were seen in many cases : however, these were usually quite small and were not related to changes in the parenchymal cells. In Case 9, four biopsies were done at weekly intervals. In the first biopsy, when the total bilirubin was 4.5 mg. the liver cells showed wide-spread cloudy swelling with-a few areas of centrilobular degeneration. One week later when the serum bilirubin had fallen to 1.7 mg. there was little change in the biopsy appearances. However, by the fourth week when the bilirubin was 0.7 mg. the liver cells were showing signs of recovery and cells with hyperchromatic and, occasionally, two nuclei were seen. Bile thrombi were seen in two cases (2 and 6). Fine granular brown pigment, which stained dark blue with Schmorl's lipofuscin method, was seen in Cases 3, 4, 5, 6 and 11 ; its significance is not clear. Neither reticulin nor fibrous tissue was increased in a n y specimen; glycogen was invariably present, but iron pigment was not seen, nor was fat seen in the one specimen stained for this. 2)
Changes in the liver at necropsy Case 4. The liver showed loci of necrosis, and there were many leucocytes in the sinusoids. Case 6. The section showed cloudy swelling of the liver cells with occasional bile thrombi. Several smaller branches of the portal vein contained fibrin thrombi ; the larger branches were normal. DISCUSSION Patients with lobar pneumonia are seen commonlyin Ibadan, and as they may not be admitted to hospital unless a complicationis found it is not easy to assess how oftenjaundice OCCURS.
When our patients were first seen in hospital, the physical sign of an enlarged and tender liver could have confused the diagnosis. It is important to recognize, therefore, that when liver cell damage complicates lobar pneumonia, the patient may be thought to have a primary infection of the liver. The patients whom we have treated have done well, and jaundice has not been found to affect the outcome of their chest infection. Although two patients died, both were found at necropsy to have bilateral lobar pneumonia which might well have proved fatal even if they had not been jaundiced. There is no reason to believe, from our small series of patients, that jaundice in the adult Nigerian with pneumonia is an ominous sign. It is well known that some infections are accompanied by haemolysis which causes jaundice. However, in only one of our patients (Case 9) was haemolysis found, and in her it was transient. It is significant that her liver showed cell damage similar to that in the other cases studied. Glucose-6-phosphate-dehydrogenase deficiency was not sought in our patients, and although this may predispose to haemolysis, the deficiency was not found in a smaller series of Nigerian patients with jaundice and pneumonia studied at Ibadan (ABRAHAMS and GILLES,pers. commun.). Jaundice in lobar pneumonia has been attributed to damage of liver cells, but the evidence has been based on biochemical tests of liver function (ELTON, 1931 ; ZXMMERMANand THOMAS,
PLATE I
CASE
No. 6. Section showing cloudy swelling of liver cells with degenerative changes and loss of nuclei in parenchyma. H & E x 380.
PLATE
CASE No. sinusoids.
II
Many inflammatory cells in a portal tract and in The liver cells show pleomorphic and hyperchromatic double nuclei. H & E x 190.
8.
ELIZABETH W.
H A L L A N D E. H .
O. P A R R Y
211
1950), which are less reliable in patients with fever. For example, HICKS et al. (1948) showed that spontaneous or artificially-induced fever profoundly affected bromsulphthalein excretion and cephalin cholesterol flocculation. In our patients, however, more specific laboratory tests have given evidence of hepatocellular damage, notably the high conjugated serum bilirubin, the presence of bile and urobilinogen in the urine, and the serum albumin, which was low at first and rose later, a change observed also by MOEN and REIMANN (1933) in patients with pneumonia. The underlying anatomical changes in the liver, commonly cloudy swelling or necrosis of the parenchymal cells, with leucocytes in the sinusoids and portal tracts, indicate an acute inflammation of the liver. The changes are of course very similar to those which are found in the early stages of infective hepatitis (DIBLE et al., 1943). However, it has not been possible to correlate the histological changes with the clinical and biochemical -findings, either in the acute phase, or during recovery. Case 6 may be an exception for the acute phase ; this subject had a serum bilirubin of 16.4 mg. and his liver showed extensive changes with necrosis of liver cells (Plate 1). The serial biopsies in Case 9 show that the cells of the liver may be abnormal, for at least 4 weeks after the pneumonia has resolved. Although this patient's clinical jaundice may have been due to haemolysis, the biopsy specimens show the same type of damage as patients without haemolysis had. Although our results have shown damaged liver cells in these patients with pneumonia, no factors which determine whether such damage occurs have been established. It is obvious that the number and virulence of the organisms on the one hand, and the resistance of the patient on the other, are critical. Previous writers have isolated the pneumococcus from their patients' sputum (HARriS, 1927), and although this organism was not cultured in our patients, and was seen only in five, the clinical picture was typical of pneumococcal pneumonia. We assume that the pneumococcus is hepatotropic, and we may well have seen patients with very virulent strains of the organism, but if this is so, it is not easy to explain why deep jaundice did not occur in patients with the most severe pneumonia, a fact which ZIMMERMANand THOMAS (1950) also reported. We have also found evidence of transient renal tubular damage in other jaundiced patients with lobar pneumonia, and this also suggests that the organisms are particularly virulent. Although pre-existing liver disease might be suspected in patients who become jaundiced during an acute infection, our specimens of liver have not shown chronic changes, except the non-specific and unexplained lymphocytic infiltration described above. Also, follow-up tests of hepatocellular function have been normal. We cannot deny that high fever may have been an added cause of damage to the liver cells (BRADCEN, 1942), but the height of fever never corresponded to the depth of jaundice. A possible reason why our patients have become jaundiced is undernutrition. The work of TUm~ER et al. (1943)and BENT et al. (1945) is particularly interesting and could well be relevant in Nigeria. They found that liver cell damage developed in dogs in which they induced lobar pneumonia, but only if the dogs' diet for the preceding 3 to 7 weeks had been deficient in protein and the B group vitamins of yeast. SUMMARY
I) Jaundice complicating lobar pneumonia has been studied in II adult Nigerian patients. The Jiver was usually large and tender during the acute pneumonia.
212
LOBAR PNEUMONIA W I T H JAUNDICE I N NIGERIANS
T h e prognosis of pneumonia in these patients has not been made worse by jaundice. 2) T h e results of biochemical tests, and studies of biopsy specimens of the liver, show that the jaundice is due to liver cell damage. The histological changes in the liver are described. REFERENCES BENT, M. J., TURNER, E. L., HOLLOWAY,G. D. & Cm~F, J. R. (1945). Sth. reed. ft., 38, 730. BtaAGDEN, J. H. (1942). ft. din. lnvest., 27, 580. DIBLE, J. H., McMxcH~L, J. & SrI~LOCK. S. P. V. (1943). Lancet, 2, 402. ELTON, N. W. (1931). ft. Lab. din. Med., 17, 216. G~avIN, I. P. (1836). Sth. Med. Surg., 1, 537. HARMS, B. R. (1927). ft. din. lnvest., 4, 211. HICKS, M. H., HOLT, H. P., G t n E ~ T , J. L. & LnWLL, B. S. (1948). 1bid., 27, 580. MOEN, J. K. & R s I ~ , H. A. (1933). 1bid., 12, 589. TROWELL,H. C. (1960). Non-Infective Disease in Africa, p. 36. London : Edward Arnold. TURNER, E. L., BENT, M. J., HOLLOWAY,G. D. & CUFF,J. R. (1943). Sth. med. ft., 36, 603. ZIMMERMAN, H. J. & THOMAS, L. J. (1950). ft. Lab. din. Med., 35, 556.
Vol. 57. No. 3.
May, 1963.
LOBAR PNEUMONIA
WITH JAUNDICE IN ADULT
NIGERIANS
BY
*ELIZABETH W. HALL, M.B. AND **E. H. O. PARRY, M.R., M.R.C.P.t
(From the Departments of Pathology and Medicine, University College Hospital, Ibadan, Nigeria.) It has been known for a long time that jaundice may complicate lobar pneumonia, and many reports have appeared since GARVIN (1836) wrote on " Pneumonia Biliosa." TROWELL (1960) suggested that the African with pneumonia may be particularly liable to become jaundiced. ZIMMERMANand THOMAS (1950) reviewed the earlier descriptions and concluded from these, and from 13 patients whom they studied, that the jaundice was hepatocellular in origin. T h e present study was done to investigate the jaundice further, and particularly to study changes in hepatic histology during the acute chest infection, previous studies having been limited to postmortem material. THE PATIENTS STUDIED AND THE METHODS USED
Eleven Nigerian patients admitted to University College Hospital, Ibadan, were studied. The criteria used for inclusion in this series were the signs of clinical jaundice and of classical lobar pneumonia, confirmed by radiograph of the chest. Ten patients were men ; there was one woman. Standard laboratory methods were used for serum and urine biochemical tests. Pereutaneous needle biopsy of the liver, using the Terry modification of the Gillman needle, was done from the epigastric approach to avoid infected lung and pleura. Parenteral vitamin K1 was given for 3 days before the biopsy, which was uneomplicated in every patient. The biopsies were done during the first week in all patients and serially during recovery in Case 9. All the biopsy specimens were fixed in 10 per cent. formol saline and stained by haematoxylin and eosin, silver stains for reticulin, Van Gieson, periodic aeid Schiff, phosphotungstic acid haematoxylin (PTAH) and Mallory's triehrome stain. CLINICAL FEATURES
Symptoms and Signs T h e patients had had chest symptoms for between 3 and 7 days. T w o said that their illness began with cough and jaundice. T h e r e were physical signs of lobar pneumonia in all patients and their temperatures were between 101 and 104.8°F. Seven patients had right lower lobe pneumonia, sometimes with infection in the right middle lobe also, or with signs at the base of the left lung. T w o had left lower lobe pneumonia, one left upper lobe pneumonia, and one right upper lobe pneumonia. T h e liver was enlarged in every patient and was tender in eight (Table I). * Seconded from the Royal Free Hospital School of Medicine. **Seconded from the Hammersmith Hospital and Postgraduate Medical School. t We are indebted to the physicians of University College Hospital, Ibadan, for permission to study patients under their care, to Professors K. R. Hill and G. M. Edington for reading the manuscript, and to Mr. F. E. Speed of the Medical Illustration Unit, University College Hospital, Ibadan, for the photographs.
ELIZABETH W .
TABLE I. Case
207
H A L L AND E. H. O. PARRY
Clinical features. Site
Temp.(°F.)
* Liver
Response to penicillin
Age years
Sex
15
M
R.L.L.
104.8
Good
42
M
L.U.L.
102
Good
65
M
R.L.L.
101
Good
50
M
R.L.L.
101
3T
Died
50
M
R.L.L.
103
3T
Good
38
M
R.U.L.
101
8T
Died
34
M
R.L.L.
103
3T
Poor I
31
M
R.L.L.
103
3T
27
F
L.L.L.
104
6T
Good
10
25
M
L.L.L.
104
6T
Good
11
40
M
R.L.L.
102
6T
Good
Good
* Figures represent size in liver in cm. below costal margin. (T = tender).
Course of the Disease Two of the patients died ; at necropsy one (Case 4) was found to have a consolidated right lung. The other (Case 6) had a consolidated right lung in which several small abscesses had formed. Eight of the survivors did very well when treated with penicillin only ; one only needed tetracycline because his pneumonia was slow to resolve. In the survivors, the jaundice faded quickly and the liver was usually no longer tender after the first week in hospital, although it was palpable in some patients for as long as 4 weeks after the acute illness was over. LABORATORY RESULTS (TABLE II)
Laboratory Remits (Table II) Culture of the sputum was not helpful : some patients could not produce sputum and others had had an injection of an antibiotic before admission. Although the pneumococcus was not cultured, Gram-positive diplococci were seen when the sputum was examined by Gram's stain in five patients. The serum bilirubin was high at first in all, and quickly fell to normal levels (Fig. I). The high total bilirubin was solely due to a high conjugated fraction in every patient except two (Cases 9 and 11). In six patients in whom the serum proteins were estimated on admission and after recovery, the serum albumin was low at first and invariably rose later. In Case 11 the serum glutamic oxaloacetic transaminase was consistently high during the first week (83 units, 69 units, 53 units/ml.), but the serum glutamic pyruvic transaminase was within normal limits (15 units, 21 units, 26 units/ml.). The direct Coombs' test was
208
LOBAR
PNEUMONIA
WITH
JAUNDICE
IN
NIGERIANS
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ELIZABETH W. HALL AND E. H. O. PARRY
209
18".
" • 16-
I
0 "~ 14FIG I. The total serum bilirubin during the course of lobar pneumonia.
12I0-
42-
I
7
14
21
DAYS
positive in only one of eight patients so tested. This patient, however, had a positive test only during the first week, and was found to have a non-specific cold antibody, and a warm antibody, apparently auto-immune and probably C -- C w. A red cell survival study using Cr51 was done during this patient's second week in hospital and gave an uncorrected half life of 27 days (Normal 24-34 days). The urine commonly contained bile, urobilinogen, and protein. Thick films of blood were not stained routinely for malaria parasites ; however, in no case were parasites seen in a thin film stained by Leishman's method. H I S T O L O G Y OF T H E L I V E R
1) Liver biopsy In every case the liver was abnormal. There were three consistent findings : first, cloudy swelling of parenchymal cells ; second, patchy areas of pleomorphic liver cells and nuclei ; and third, infiltration of portal tracts by inflammatory cells with occasional loci of inflammatory cells in the parenchyma. Cloudy swelling in some cases was wide spread, but more often it tended to be focal, while the remaining cells were pleomorphic. The pleomorphic liver cells occasionally showed double nuclei and more often hyperchromatic nuclei, suggesting regeneration of cells. Foci of degenerate or necrotic cells, often centrilobular, were seen in Cases 3, 4, 6, and 7 (Plate 1). The portal tracts in every cases were infiltrated by cells, usually lymphocytes, with occasional plasma cells and polymorphs (Plate 2). Although the portal tracts of livers studied at Ibadan often show excessive leucocytes, our material has shown even
210
LOBAR PNEUMONIA
WITH
JAUNDICE IN NIGERIANS
more cells than usual. In each biopsy the sinuses contained leucocytes comparable to the peripheral blood count. Foci of lymphocytes and histiocytes in the parenchyma were seen in many cases : however, these were usually quite small and were not related to changes in the parenchymal cells. In Case 9, four biopsies were done at weekly intervals. In the first biopsy, when the total bilirubin was 4.5 mg. the liver cells showed wide-spread cloudy swelling with-a few areas of centrilobular degeneration. One week later when the serum bilirubin had fallen to 1.7 mg. there was little change in the biopsy appearances. However, by the fourth week when the bilirubin was 0.7 mg. the liver cells were showing signs of recovery and cells with hyperchromatic and, occasionally, two nuclei were seen. Bile thrombi were seen in two cases (2 and 6). Fine granular brown pigment, which stained dark blue with Schmorl's lipofuscin method, was seen in Cases 3, 4, 5, 6 and 11 ; its significance is not clear. Neither reticulin nor fibrous tissue was increased in a n y specimen; glycogen was invariably present, but iron pigment was not seen, nor was fat seen in the one specimen stained for this. 2)
Changes in the liver at necropsy Case 4. The liver showed loci of necrosis, and there were many leucocytes in the sinusoids. Case 6. The section showed cloudy swelling of the liver cells with occasional bile thrombi. Several smaller branches of the portal vein contained fibrin thrombi ; the larger branches were normal. DISCUSSION Patients with lobar pneumonia are seen commonlyin Ibadan, and as they may not be admitted to hospital unless a complicationis found it is not easy to assess how oftenjaundice OCCURS.
When our patients were first seen in hospital, the physical sign of an enlarged and tender liver could have confused the diagnosis. It is important to recognize, therefore, that when liver cell damage complicates lobar pneumonia, the patient may be thought to have a primary infection of the liver. The patients whom we have treated have done well, and jaundice has not been found to affect the outcome of their chest infection. Although two patients died, both were found at necropsy to have bilateral lobar pneumonia which might well have proved fatal even if they had not been jaundiced. There is no reason to believe, from our small series of patients, that jaundice in the adult Nigerian with pneumonia is an ominous sign. It is well known that some infections are accompanied by haemolysis which causes jaundice. However, in only one of our patients (Case 9) was haemolysis found, and in her it was transient. It is significant that her liver showed cell damage similar to that in the other cases studied. Glucose-6-phosphate-dehydrogenase deficiency was not sought in our patients, and although this may predispose to haemolysis, the deficiency was not found in a smaller series of Nigerian patients with jaundice and pneumonia studied at Ibadan (ABRAHAMS and GILLES,pers. commun.). Jaundice in lobar pneumonia has been attributed to damage of liver cells, but the evidence has been based on biochemical tests of liver function (ELTON, 1931 ; ZXMMERMANand THOMAS,
PLATE I
CASE
No. 6. Section showing cloudy swelling of liver cells with degenerative changes and loss of nuclei in parenchyma. H & E x 380.
PLATE
CASE No. sinusoids.
II
Many inflammatory cells in a portal tract and in The liver cells show pleomorphic and hyperchromatic double nuclei. H & E x 190.
8.
ELIZABETH W.
H A L L A N D E. H .
O. P A R R Y
211
1950), which are less reliable in patients with fever. For example, HICKS et al. (1948) showed that spontaneous or artificially-induced fever profoundly affected bromsulphthalein excretion and cephalin cholesterol flocculation. In our patients, however, more specific laboratory tests have given evidence of hepatocellular damage, notably the high conjugated serum bilirubin, the presence of bile and urobilinogen in the urine, and the serum albumin, which was low at first and rose later, a change observed also by MOEN and REIMANN (1933) in patients with pneumonia. The underlying anatomical changes in the liver, commonly cloudy swelling or necrosis of the parenchymal cells, with leucocytes in the sinusoids and portal tracts, indicate an acute inflammation of the liver. The changes are of course very similar to those which are found in the early stages of infective hepatitis (DIBLE et al., 1943). However, it has not been possible to correlate the histological changes with the clinical and biochemical -findings, either in the acute phase, or during recovery. Case 6 may be an exception for the acute phase ; this subject had a serum bilirubin of 16.4 mg. and his liver showed extensive changes with necrosis of liver cells (Plate 1). The serial biopsies in Case 9 show that the cells of the liver may be abnormal, for at least 4 weeks after the pneumonia has resolved. Although this patient's clinical jaundice may have been due to haemolysis, the biopsy specimens show the same type of damage as patients without haemolysis had. Although our results have shown damaged liver cells in these patients with pneumonia, no factors which determine whether such damage occurs have been established. It is obvious that the number and virulence of the organisms on the one hand, and the resistance of the patient on the other, are critical. Previous writers have isolated the pneumococcus from their patients' sputum (HARriS, 1927), and although this organism was not cultured in our patients, and was seen only in five, the clinical picture was typical of pneumococcal pneumonia. We assume that the pneumococcus is hepatotropic, and we may well have seen patients with very virulent strains of the organism, but if this is so, it is not easy to explain why deep jaundice did not occur in patients with the most severe pneumonia, a fact which ZIMMERMANand THOMAS (1950) also reported. We have also found evidence of transient renal tubular damage in other jaundiced patients with lobar pneumonia, and this also suggests that the organisms are particularly virulent. Although pre-existing liver disease might be suspected in patients who become jaundiced during an acute infection, our specimens of liver have not shown chronic changes, except the non-specific and unexplained lymphocytic infiltration described above. Also, follow-up tests of hepatocellular function have been normal. We cannot deny that high fever may have been an added cause of damage to the liver cells (BRADCEN, 1942), but the height of fever never corresponded to the depth of jaundice. A possible reason why our patients have become jaundiced is undernutrition. The work of TUm~ER et al. (1943)and BENT et al. (1945) is particularly interesting and could well be relevant in Nigeria. They found that liver cell damage developed in dogs in which they induced lobar pneumonia, but only if the dogs' diet for the preceding 3 to 7 weeks had been deficient in protein and the B group vitamins of yeast. SUMMARY
I) Jaundice complicating lobar pneumonia has been studied in II adult Nigerian patients. The Jiver was usually large and tender during the acute pneumonia.
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LOBAR PNEUMONIA W I T H JAUNDICE I N NIGERIANS
T h e prognosis of pneumonia in these patients has not been made worse by jaundice. 2) T h e results of biochemical tests, and studies of biopsy specimens of the liver, show that the jaundice is due to liver cell damage. The histological changes in the liver are described. REFERENCES BENT, M. J., TURNER, E. L., HOLLOWAY,G. D. & Cm~F, J. R. (1945). Sth. reed. ft., 38, 730. BtaAGDEN, J. H. (1942). ft. din. lnvest., 27, 580. DIBLE, J. H., McMxcH~L, J. & SrI~LOCK. S. P. V. (1943). Lancet, 2, 402. ELTON, N. W. (1931). ft. Lab. din. Med., 17, 216. G~avIN, I. P. (1836). Sth. Med. Surg., 1, 537. HARMS, B. R. (1927). ft. din. lnvest., 4, 211. HICKS, M. H., HOLT, H. P., G t n E ~ T , J. L. & LnWLL, B. S. (1948). 1bid., 27, 580. MOEN, J. K. & R s I ~ , H. A. (1933). 1bid., 12, 589. TROWELL,H. C. (1960). Non-Infective Disease in Africa, p. 36. London : Edward Arnold. TURNER, E. L., BENT, M. J., HOLLOWAY,G. D. & CUFF,J. R. (1943). Sth. med. ft., 36, 603. ZIMMERMAN, H. J. & THOMAS, L. J. (1950). ft. Lab. din. Med., 35, 556.