The case that is about to be discussed here revolves around a patient diagnosed with pulmonary tuberculosis. The patient that was clerked, Mrs A, was a 61 year old woman. She was a Malay housewife. Her Body Mass Index value of 26.0 kg/m2 based on her height of 1.58 m and weight of 65 kg indicated that she fell into the overweight range.

The patient was admitted to the Accident & Emergency mode transferred in from another hospital via an ambulance. She presented symptoms such as shortness of breath(SOB) and her respiratory rate was 20 breaths per minute. She appeared pale and weak and her blood glucose levels were low (2.1 mmol/l) and her blood pressure values indicated she was hypertensive with a value of 152/93 mmHg. Upon physical examination, mild leg swelling was observed.

Based on her past medical history, patient was diagnosed with pulmonary tuberculosis for the past 3 months, hypertension for the past 5 years, diabetes for the past 5 years and advanced renal failure for the past 6 months.

Upon enquiry, she was seen to be a non-smoker and a non alcoholic. Patient lived with her daughter.

Several investigations were performed to evaluate the patient’s condition. A positive sputum smear test indicated that the patients tuberculosis was still active. Upon renal function assessment, creatinine clearance was calculated and a value of 5.5 ml/min indicated Stage 5 renal failure. Her potassium and urea levels were also above range based on Table 1. Upon haematology assessment, her low blood sugar levels indicated hypoglycaemia and patient’s haemoglobin count was also low signifying anemia. Chest X ray was conducted on this patient and minor lesions at the apical segments of the upper lobe were seen. This is a typical radiographic representation of patients with tuberculosis.

Table 1: Results of the investigations performed

Laboratory Test

Readings

Normal range

Sputum Smear Test

Positive

–

Renal Function

Creatinine, Cr

Urea

Potassium, K+

912 μmol/l

37.8 mmol/l

5.5 mmol/l

44-80 μmol/l

1.7 – 8.5 mmol/l

3.5 – 5.0 mmol/l

Haematology Assessment

Blood Sugar Level

Haemoglobin

2.1 mmol/l

9.8 g/dl

4.5 – 6.0 mmol/l

13.5 – 18 g/dl

Table 2 provides details about patient’s drug history giving information about patient’s drugs and their respective doses. Upon interview, patient informed that she had not been purchasing any over the counter medications. She also has no known drug allergy.

Table 2 : Drug History and their respective doses and their indication

Drug

Dose

Duration

Indication

Rifampicin

300 mg OD

2 months

Anti TB

Isoniazid

200 mg OD

2 months

Anti TB

Pyrazinamide

750 mg OD

2 months

Anti TB

Ethambutol

600 mg OD

2 months

Anti TB

Pyridoxine

20 mg OD

2 months

Treatment of neuropathy

Gliclazide

40 mg OD

5 years

Anti diabetic

Prazosin

2 mg TDS

5 years

Anti Hypertensive

Furosemide

80 mg OD

5 years

Anti Hypertensive

Nifedipine

20 mg TDS

5 years

Anti Hypertensive

Based on the investigations performed, the patient was diagnosed to be suffering from pulmonary tuberculosis and diabetes mellitus.

Patient’s daily condition was monitored and appropriate management was undertaken to control the patient’s condition. Patient’s overall progress is tabulated in the table 3 and the observation is recorded.

Table 3 : Patient’s clinical progress and management

Day

Clinical Progress

Management

1

Hypoglycemia = 2.1 mmol/L

AFB test positive

Chest X ray performed

SOB

Hyperkalaemia ( 5.5 mol/L)

Anemic ( 9.8 g/dL)

BP : 152/93 mmHg

Strict fluid intake

IV Dextrose 10%/24 hours

Refer to chest physician

Lesions at upper lobes

NPO2 to resolve SOB

Start on Calcium polystyrene

Start Ferrous (IV) sulphate

Start antihypertensives

Monitor input & output

2

AFB test +ve

Blood Sugar Level = 3.0 mmol/L

BP : 140/90 mmHg

Start TB regimen (EHRZ)

Continue IV Dextrose 10% & Monitor Blood Glucose

Continue antihypertensives

3

Blood Sugar level = 3.2 mmol/L

Severe renal impairment ( CrCl =5.6 ml/min )

Chest X ray done time to time

BP : 130/70 mmHg

Continue dextrose infusion

Send patient for dialysis

Lesions still present

Continue antihypertensives

4

No SOB

Hypoglycaemia resolved = 5.5 mmol/L

AFB +ve

BP : 130/75 mmHg

Remove nasal prongs

Stop Dextrose. Monitor blood glucose

Continue TB regimen

6

K+ level in normal range ( 4.5 mmol/L)

Blood Sugar level = 6.0 mmol/L

CrCl = 7.7 ml/min

BP : 130/65 mmHg

Stop Calcium polystyrene.

Monitor blood glucose

Send patient for dialysis

8

Hyperglycemia = 11.1 mmol/L

BP : 125/75 mmHg

Start on Insulin

DM counselling

13

AFB -ve

DXT = 10.2 mmol/L

BP : 120/70 mmHg

Transfer out of isolation

Continue insulin. Monitor blood glucose

Based on patient’s presentation and results from investigations performed on day 1, patient was started on dextrose and her blood glucose levels were regularly monitored. Based on patient’s previous history, a sputum smear test was ordered and two consecutive positive results resulted in the patient being referred to the chest physician. A chest X ray was performed and lesions in the apical segment were present. To resolve patient’s SOB, patient was started on Nasal Prongs at 3L/min. To control her hyperkalemia, patient was given calcium polystyrene sulphonate powder. Patient was also started on ferrous sulphate infusion to help her cope with her anaemia. A strict fluid intake was imposed on patient to resolve her leg swelling and this was monitored through an input output chart. Her blood pressure (BP) levels were also elevated and patient was given antihypertensives such as nifedipine, prazosin and furosemide to control her BP.

On day 2, her sputum smear remained positive and patient was commenced on the intial phase therapy for tuberculosis which consists of isoniazid, rifampicin, pyrazinamide and ethambutol. There was not much improvement in her blood glucose levels and patient was remained on the dextrose infusion. Moving on to day 3, not much improvement was observed and due to patient’s deteriorating renal function, patient was sent for peritoneal dialysis.

By day 4, patient could breath normally and no shortness of breath was seen. Nasal prongs were removed. When her blood glucose levels were monitored, the results indicated patient was within the normal range and dextrose was withheld. Blood glucose levels were still monitored to prevent sudden drops and increase in blood glucose. Her potassium levels were within range by day 6 and calcium polystyrene sulphonate was stopped and potassium levels were monitored as well.

Patient suffered from a hyperglycemia episode on day 8 and the patient was given biphasic insulin to treat this condition. By this day, her BP was also in the normal range but the antihypertensives were still continued. On day 13, patient was transferred out of the isolation ward as her sputum smear test produced negative results. Patient’s condition for tuberculosis was still being monitored. Her blood glucose levels were still in the high range and patient was to be continued on insulin.

To summarize this case, patient’s active tuberculosis state should be managed well to ensure patient does not suffer from further complications that might arise in the future. Patient’s history was well noted and this helped in treating the patient in early stages. Adequate investigations were performed to assist the healthcare professional team to diagnose the patient and also to manage the patient. Patient was admitted for a long period but the appropriate management that was undertaken resulted in improvement in patient’s condition. Further care for the patient would improve the patient’s quality of life in the future

Pathophysiology and Incidence

Tuberculosis (TB) is an infectious disease that has plagued many nations across the world. Based on the report by World Health Organization (WHO), almost 9.4 million cases of TB were reported 3. It is highly common of those with TB to contract the Human Immunodeficiency Virus (HIV) and a prevalence of almost 1.7 million deaths from TB among HIV-negative people was recorded around the globe 3. In the United Kingdom, an increasing trend in TB incidence has been reported and this is shown in Figure 1. In 2008, a rate of 14 per 100 000 population in the UK were reported to be suffering from TB 4. Malaysia on the other hand has a higher record of TB cases with 103 per 100 000 population being reported in 2007. Table 1 summarizes some of the data obtained from World Health Organization 3.

Figure 1: Number of TB cases reported in the UK from 2000 to 2008 4

Table 1: Statistics displaying number of TB cases in Malaysia in 2007 3

All

In HIV + people

Incidence

All forms of TB (per 100 000 population)

103

17

Mortality

All forms of TB (per 100 000 population)

121

8.3

Multi-drug Resistant TB (MDR-TB)

MDR-TB among new cases (%)

0.1

–

Notified relapse cases (per 100 000 pop/yr)

61

–

The bacteria that is responsible for this disease is the acid fast bacilli aerobic bacterium Mycobacterium tuberculosis 1. A key feature that enables this bacterium to survive would be its unique cell wall. Mycolic acids are linked covalently to arabinogalactan that provides a barrier to host defense mechanism. Antigens such as lipoarabinomannan present on the exterior of the cell wall facilitate the survival of the organism within macrophages 1. Tuberculosis is spread usually spread within droplets containing the microorganism that are produced when an infected person coughs, sneezes or even talks 1,2. Figure 1 gives a schematic impression of the progression of the disease. The inhaled droplets are initially trapped by dendritic cells that act to expel any foreign particles out. Most mycobacteria are able to surpass this defense mechanism and travels further to the alveoli where it gets ingested by macrophages 1. It then undergoes intracellular replication that might take duration of 4 to 6 weeks. Cytokines are further released during this period and this attracts T lymphocytes that are involved in mediating a cell immune response. The next natural defense system step would be the formation of granuloma that contains the activated T lymphocytes and macrophages. These nodular lesions disable further spread of the disease as the environment within restricts the growth of the bacilli and a latent period occurs 1. For less immunocompetent individuals, the granuloma will not be able to contain the bacilli and the active disease takes form 1.

Figure 1: Image depicting the progress of tuberculosis 2

The diagnostic tests available are summarized in Table 2. TB can be divided to latent and active and to diagnose each different test has been recommended. For latent TB, Mantoux test can be carried out and those with positive results can be considered for QuantiFERON TB test 5. To diagnose active pulmonary TB, a chest X-ray would be taken followed by multiple sputum samples that are sent for smear test 5.

Table 2: Diagnostic tests available for tuberculosis 1

Variable

Purpose

Time required for results

Sputum smear

Detect acid fast bacilli

< 24 hours

Sputum culture

Identify M tuberculosis

3-6 weeks with solid

media, 4-14 days with

high-pressure

liquid chromatography

Tuberculin skin test/ Mantoux

Detect exposure to mycobacteria

48 – 72 hours

QuantiFERON TB-test

Measure immune reactivity to M tuberculosis

12 – 24 hours

Chest radiography

Visualize lobar infiltrates with cavitation

Minutes

The drugs that are commonly used in tuberculosis are isoniazid, rifampicin, pyrazinamide and ethambutol. Rifampicin is a bactericidal agent that inhibits RNA synthesis by binding to the ß subunit of RNA polymerase. It can be given via oral administration and can even be distributed to the central nervous system due to its lipophilicity. Metabolism of this drug occurs in the liver and it is usually excreted in the urine. Isoniazid is a bactericidal pro-drug that inhibits ketoenoylreductase enzyme, InhA, that is responsible in synthesizing mycolic acids. Isoniazid can be administered orally, intramuscularly or intravenously and is acetylated in the liver and subsequently excreted in the urine. Pyridoxine 10 mg is given concurrently to minimize this risk. Pyrazinamide is another prodrug that is activated by nicotinamidase to pyrazinoic acid. This component at low pH carries proton into the cell and collapses the proton motive force present in the mycobacterium which results in cell death. It is only bactericidal against non growing bacilli forms..