A case of hyperuricemia in the ICU

HOSP # WARD Surgical ICU
CONSULTANT Heleen Vreede / George van der Watt   DOB/AGE 30 year Male

Abnormal Result

The result upon the query being raised by the reviewer was a uric acid of 0.95 mmol/L (0.21-0.43 mmol/L). Three days prior to this result, the patient had a uric acid serum concentration of 0.38 mmol/L.

Presenting Complaint

The patient presented to the hospital with a history of a swollen tonsil unilaterally. This worsened over few days to a severe infection (sepsis) as described below.

History

No significant history. Patient reported sober habits.

Examination

At initial presentation, the patient appeared to have a suppurative tonsillitis. The tonsillitis later developed into a retropharyngeal abscess and soon extended into the thorax, forming a pericardial abscess, which is what was found clinically at the time of admission to Groote Schuur Hospital.

Laboratory Investigations

Date: newest to oldest (only chemistry results included)

Other Investigations

CT scan: images to follow

Final Diagnosis

Retropharyngeal abscess progressing to a thoracic abscess and causing overt signs and symptons of heart failure.

Patient required a thoracotomy and pericardial drainage of the abscess.

Take Home Messages

  • Do not take tonsillitis lightly. If not adequately managed, it may cause serious complications.
  • Elevated Uric acid is a risk factor for acute kidney injury. This may be by means of acute gouty crystal deposition, but other crystal-independent roles has also been described.
  • Uric acid concentration will rise significantly in severe infection, most likely due to the fast tempo of tissue or DNA turnover, both by bacteria and host tissue breakdown and repair. Uric acid is a product of the metabolic breakdown of purine nucleotides.
  • Uric acid, being a heterocyclic compound, I thought could interfere in various assays, and I thought even in the Jaffe reaction for creatinine, but it doesn’t seem to be a common interferent when doing a quick literature search.
  • Uric acid appears to be the major anti-oxidant in human serum constituting around 61% of total anti-oxidant activity, evidenced by Maxwell et al.:
  • Relative contribution to total serum anti-oxidant activity in this study was: urate 65.1%, vitamin C 8.7%, vitamin E 10.6%, vitamin A 5.7%, thiols 7.8% (as in albumin) and bilirubin 1.9%.
  • One immediately thinks that a patient with such a rapidly progressing infection has to be immunocompromised, the most common cause(s) in South Africa being HIV or diabetes mellitus. This patient however was HIV negative, according to HIV ELISA and did not have reported signs and symptoms of diabetes.


A Case of Neurodevelopmental Delay

HOSP # WARD Neurodevelopmental clinic – Inkosi Albert Luthuli Hospital
CONSULTANT Prof. George van der Watt DOB/AGE 2y male

Abnormal Result

Urine organic acid analysis was performed upon which a big peak was seen, representative of phenylpyruvate.

Presenting Complaint

The patient was a 2 year old male evaluated at a neurology clinic for neurodevelopmental delay.

History

The patient’s brother died at 3 or 4 years of age with similar neurodevelopmental delay.

Examination

Unfortunately this information was unavailable. The clinician I got hold of at Inkosi Albert Luthuli hasn’t seen the patient himself.

Laboratory Investigations

Fig 1 – Urine organic acid screening by GCMS demonstrates elevations of the phenylketones: phenylpyruvate and 4-OH phenylpuyruvate. These findings are indicative of a diagnosis of phenylketonuria due to autosomal recessive deficiency of phenylalanine hydroxylase.

Other Investigations

The urine amino acid analysis yielded a significantly raised phenylalanine: 672 umol/L (ref <67)

Final Diagnosis

This is a case of phenylketonuria

The diagnosis is also supported by a plasma phenylalanine of 672 umol/L (ref < 67).

Take Home Messages

Build-up of phenylalanine gets metabolised to phenylpyruvate (which is seen in urine at high levels).

Phenylalanine levels >600 umol/L in serum is highly indicative of phenylketonuria

Prof. George van der Watt

Biopterin cycling defects usually cause levels >125 umol/L.

This deficiency is 4-monooxygenase deficiency.

Management of PKU is with a phenylalanine restricted diet.



Elevated anti-Thyroglobulin Antibodies

HOSP # WARD Oudtshoorn Clinic
CONSULTANT George van der Watt & David Marais DOB/AGE 66y Male

Abnormal Result

Presenting Complaint

Mr. X, a 66 year old male, complained of chest pain, was seen at the Oudtshoorn Emergency department and a myocardial infarction was excluded by three serial point-of-care (POC) Troponin I results.

History

  • Known with hypothyroidism, but the cause was not defined yet.
  • On Eltroxin 150 ug daily PO
  • No other treatment.
  • Various stool analyses had been sent in for culture, with no definitive result.

Examination

Unfortunately not known.

Laboratory Investigations

Free T4: 24.6 pmol/L (7.6 – 16.1 pmol/L)

Anti-Thyroglobulin Antibody levels were elevated at 1944 U/mL (ref. <115 U/mL).

Other Investigations

Later, by retrospective viewing of the patient’s results it was revealed:

Total Cholesterol (TC) was elevated at 7.6 mmol/L. Hypothyroidism is associated with hypercholesterolemia. It can be concluded by the retrospective overview of results that upon an episode of hypothyroidism, the patient had hypercholesterolemia. This was most likely due to cessation of Thyroxine treatment, to whatever reason.

Index sample marked by the yellow shade. TC result which is raised (upper left corner) corresponds to the severely hypothyroid episode as revealed by the low T4 on that same sample.

Investigations also confirmatory for auto-immune hypothyroidism are:

  • Anti-Thyroid peroxidase antibodies
  • Anti-TSH receptor antibodies

Final Diagnosis

Auto-immune hypothyroidism

Take Home Messages

Interestingly, numerous patients with hypothyroidism is diagnosed at our Lipid Clinic at Groote Schuur Hospital. Patients are being referred for hypercholesterolaemia. Generally referral to this clinic happens when TC > 7.5 mmol/L. These patients are referred as presumed to have familial hypercholesterolaemia, but upon further work-up it is found that many of these patients have long-standing untreated hypothyroidism.

Prevalences of antithyroid antibodies as summarized by Up-to-date:

Image result for auto-immune hypothyroidism antibodies"


Thyroid Carcinoma

HOSP # WARD Nuclear Medicine
CONSULTANT   DOB/AGE 62 y Female

Abnormal Result

Thyroglobulin value of <0.1 ug/L upon signing results out.

Presenting Complaint

Patient presented with a neck “swelling” in October 2016. Systemic complaints were not inquired, but none was reported.

History

TFT: euthyroid since presentation when the thyroid functions were first tested in 2016.

Examination

A solitary thyroid nodule was found in the neck, moving with swallowing.

Laboratory Investigations

TFT: euthyroid upon presentation, which is clear from the table below.

  07/11/2019 08/08/2019 21/06/2019 20/02/2019 20/11/2018 26/09/2018 21/09/2018 05/07/2018 13/06/2018 29/05/2018 07/05/2018 08/01/2018 05/04/2017 26/10/2016
TSH δ- 1,49   δ- 7,07 H δ+62,97 H  0.01 L δ- 0.01 L        δ+88,52 H  3,84    6,35 H δ+ 9,88 H  2,86    4,05   δ+ 3,26    1,62  
Free T4  21,4   δ+ 22,3 H δ-  3.0 L δ- 29,8 H δ+ 42,7 H        δ-  3,1 L  17,3   CEGK  15,1                 δ+ 14,9      12  
Free T3                                                                                       4,8         
Thyroglobulin (3.5-77.0 ug/L)  <0.1 L  <0.1 L   0.1 L  <0.1 L δ- <0.1 L   7,9            8,8     7,6                                     
Anti-thyroglobulin Ab (<115 U/ml)   <10     <10     <10     <10     <10      11             14      11                                     

From results above it can be seen that the patient was euthyroid upon presentation (in 2016 and later until excision – highlighted in bold)

Hemithyroidectomy was done in May 2018, and another hemithyroidectomy in September 2018, thus the thyroglobulin after the first and second surgery was still detectable, but absent after September 2018.

Other Investigations

Ultrasound upon first presentation was indicative of a “suspicious nodule” in the thyroid gland.

Final Diagnosis

PATHOLOGICAL DIAGNOSIS – excision biopsy of nodule (17/01/2018)

Specimen A:
Right lobe of thyroid, hemithryoidectomy:
Encapsulated follicular variant of papillary thyroid carcinoma
Specimen B:
Right cervical lymph node (Level VI), biopsy:
Negative for malignancy (0/1)

PATHOLOGICAL DIAGNOSIS – left thyroid lobectomy (11/05/2018):

Left lobe of thyroid, excision: Negative for malignancy

PATHOLOGICAL DIAGNOSIS:

Right thyroid, lobectomy: Negative for malignancy (05/09/2018):

Take Home Messages

  • Thyroglobulin level is directly proportional to thyroid tissue present in vivo, hence is a useful tumour marker for thyroid cancer.
  • Anti-thyroglobulin antibody level is tested with Thyroglobulin to exclude false low values of thyroglobulin. If Anti-thyroglobulin Ab levels are increased with a decreased thyroglobulin level, the decrease in tumour marker is likely due to immunological clearance of the thyroglobulin and the result is hence likely false. This is the reason for the following canned text in TrakCare when the thyroglobulin level measures low:

The presence of thyroglobulin antibodies may interfere with the
thyroglobulin assay. The result of this test must be treated with reserve
if the patient has a positive thyroglobulin antibody test.

TrakCare canned text for low thyroglobulin

  • Upon total removal of the thyroid, thyroid replacement therapy is necessary, preferably slightly hyperthyroid levels to suppress TSH, and hence prevent tumour growth, as is also evidenced by this patient’s TSH and free T4 results.
  • As with most other tumour markers, thyroglobulin should be used for follow-up as a proxy of tumour size or regression.



Hyperaldosteronism

HOSP # WARD Murraysburg Hospital, Female Ward
CONSULTANT   DOB/AGE 51 y female

Abnormal Result

Aldosterone: 1380 pmol/L

Renin: 2.1 ng/L

Aldosterone: Renin ratio: 657.14 pmol/ng

Presenting Complaint

Uncontrolled Hypertension, unresolved on maximum dose of 3 antihypertensives.

History

Examination

Laboratory Investigations

Other Investigations

Urine electrolytes

Serum Results

Date Sodium mmol/L Potassium mmol/L eGFR ml/min GGT U/L Chol mmol/L TSH mIU/L T4 pmol/L FreeT3 pmol/L Cort nmol/L
21/04/2015          2,8   >60           5,07                              
30/11/2015          3,8     >60           4,53                              
15/11/2016          >60           4,04                              
20/03/2017                 >60           4,36                              
05/06/2018   144  3,4    56           4,39    1,79    11,9       5     394  
20/08/2018   131 4,6    42                                            
21/08/2018                                                               
24/08/2018                                                               
26/08/2018                                                               
26/08/2018                                                               
26/09/2019   139   2,4    45                  0.81                       
27/09/2019   142   2,6    43                                            
01/10/2019                                                               
02/10/2019   139   2,9    40                 CEGK                
03/10/2019                                                               
07/10/2019   138   3,9      38                                            
31/10/2019   139   1,9    30      28                                     

Urine metanephrines

Urine collection period 24  h       Reference value
Urine volume 3080 ml       
Ucreat   2,2 mmol/L       
Umetadren   160 nmol/L       
Unormetadren   870  nmol/L
dUmetadren   493  nmol/24h 152-913
dUnormetadren  2680 nmol/24h 699-2643
Umetadren:cr    73  nmol/mmol creat 17-91
Unormetad:cr   395 nmol/mmol creat 75-309

Final Diagnosis

Primary hyperaldosteronism causing secondary hypertension with accompanying renal injury.

Take Home Messages

Reference Ranges for Aldosterone:

  • Upright 70 – 1066 pmol/L
  • Supine 49 – 643 pmol/L

Screening for primary hyperaldosteronism: most sensitive when >350 pmol/L

Reference Ranges for Renin:

  • Upright: 2.7 – 27.7 ng/L
  • Supine: 1.7 – 23.9 ng/L

Beta-blockers suppress renin levels and should be stopped 2 weeks before testing.

Aldosterone: Renin Ratio:

Most sensitive when the ratio is >118 pmol/ng.

Effects of hyperaldosteronism

  • One’s expectation is a high serum sodium, but since it normalizes with an increase in fluid volume, hence hypertension as in this case, there is normal sodium.
  • Low serum potassium due to loss in urine, although this can also be normal.
  • Increased urine potassium concentration (>30 mmol/L) in a random urine specimen suggests increased mineralocorticoid effect.
  • The renin:aldosterone ratio is used to compensate for the increase in aldosterone which is caused by an increase in renin (for instance which is caused by hypovolemia or low blood pressure).
  • Some studies recently published are suggesting that the prevalence of hyperaldosteronism are significantly more than was (and is) thought, and hence urinary (24 hour) aldosterone measurement may be more accurate to screen for hyperaldosteronism. The authors of recent estimates of the prevalence of hyperaldosteronism are of opinion that hyperaldosteronism may be the cause of around 10% of unexplained “essential” hypertensives (see attached articles).
Hyperaldo-prevalence-2020Download
Primary-hyperaldo-Editorial-2020Download


Drip line contamination – Ringers Lactate

HOSP # WARD False Bay Hospital Casualties
CONSULTANT   DOB/AGE 33y Female

Abnormal Result

Urea 0.8 mmol/L; Creatinine 10 umol/L; Sodium 154 mmol/L; Potassium 5.4 mmol/L

Presenting Complaint

Above results do not make sense for a 33 year old female, except if muscle weight is extremely low.

History

Examination

N/A

Laboratory Investigations

Inspection of the sample:

Drip line contamination
On inspection of the sample it is clear that there is dilution with a clear fluid and the hematocrit is affected severely (also visible on results below).

Other Investigations

Lactate on analyser as done on serum sample: >22 mmol/L, dilution made: 1 in 10 revealed a lactate of 26.8 mmol/L in the sample. This could explain that Ringers Lactate was the contaminant in the sample, but can only be hypothesized with the available evidence.

Hematology results:

From the previous (and current) Hematology results available, it is clear that, since all values are lower than the previous day, drip line contamination is the likely cause of the low Chemistry and Hematology results.

Final Diagnosis

Take Home Messages

PDF Loading...

Lactate cannot be measured in SST (serum separator tubes) without taking into account the fact that the red cells will continue to metabolize the glucose in the sample to lactate via anaerobic metabolism through glycolysis.

Lactate concentration increases linearly over time, in whole blood. Factors affecting the rate of production are, among others:

  • Temperature
  • Glucose concentration
  • Additives in the blood tubes such as NaF

NaF inhibits enolase, an enzyme acting late in the glycolytic pathway, and has no effect on enzymes that act early in the glycolytic pathway. … Glycolysis is instantly inhibited in erythrocytes, leukocytes and platelets when the blood pH is maintained between 5.3 and 5.9 with a citrate buffer.

Sage Journals: Ann Clin Biochem 2013;50: 3–5. DOI: 10.1258/acb.2012.012135

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Composition of Ringer's lactate solution 
Image result for ringers lactate contents


Hypernatremia

HOSP # WARD Red Cross Children’s Hospital ICU
CONSULTANT Dr. S
Prof. G		 DOB/AGE 14 day old Neonate

Abnormal Result

Sodium = 198 mmol/L (H) (136-145)

Presenting Complaint

1 day of poor feeding.  Child passing very hard/ dark brown stool for the preceding 10 days.

History

Birth weight @ term: 3.380kg.  Delivered vaginally after induction of labour because of spontaneous rupture of membranes at 40 weeks gestation. Discharged home without any problems after 1 day.

Examination

On arrival at district hospital: Temp: 38oC, Sats 96% on Nasal O2, Finger prick glucose: 10mmol/L, Capillary refill time: 6 seconds,

HR: 140bpm. 

Blood gas:

pH: 7.26,

BE -16.3,

pCO­2 3.2 kPa,

Na 190.

Weight: 2.2kg (birth weight: 3.380 kg, thus 35% weight loss)

Laboratory Investigations

Other Investigations

Urine organic acid analysis by GCMS demonstrates elevation of the liver markers 4-OH-phenyllactate and 4-OH-phenylpyruvate together with lactaturia. Succinylacetone, a marker for tyrosinaemia type 1 is absent. Moderate ketonuria with elevated dicarboxylic acids C6, C8, and C10 is also present, these changes suggest a lipolytic response to catabolic or fasting stress or hypoglycaemia together with underlying hepatic dysfunction with lactataemia but are non-specific for an IMD per se. 

Final Diagnosis

Patient was pure water depleted with a sodium concentration of 198 mmol/L.  The mother was not lactating adequately despite the infant sucking well, evidenced by the fact that when expressed breast milk was tried, there was too little milk for the baby to drink.  The nurses’ notes confirmed this finding.  This finding also confirms the failure to produce stool volume and the normal urine organic acid profile with evidence of starvation / fasting stress.

Take Home Messages

When considering a patient with high plasma sodium concentration it is
important to bear in mind:

  1. Hypernatremia does not necessarily indicate an excess of extracellular sodium.  Except in rare cases of salt overload most patient with hypernatremia have a deficiency of both water and sodium, with the water deficiency being proportionally higher than that of sodium.
  2. Patients become hypernatremic because the water lost from the body exceed the intake and there is negative fluid balance.  The amount of water which a person can drink generally exceeds by far the amount lost from the body in most pathological fluid-losing disorders, eg. Diarrhoea, sweating.  Patients thus become hypernatremia due to:
    1. Too old, young or sick to drink
    2. Obstruction of oesophagus
    3. Disorders of thirst centre
    4. No access to water                          

Ref: Walmsley – Cases in Chemical Pathology 4th
ed.

It is also important:

  1. To calculate the Osmolar gap( difference between calculated and measured osmolarity)
  2. U:P osmol (>1 = hypotonic fluid depletion, pure water loss or salt gain; ~1 = osmotic diuresis; <1 = diabetes insipidus ~the various causes of nephrogenic and neurogenic DI)



Prolactin

HOSP # WARD ENT Clinic
CONSULTANT   DOB/AGE 35 Y Male

Abnormal Result

Prolactin 10 986.0 ug/L (4-15.2) 

Dilutions:

1/10  >4700;

1/100 = 10821;

1/50 = 10 986.

Presenting Complaint

Epistaxis

History

Patient with epistaxis referred to the ENT specialist clinic.  No relevant medication history.

Examination

35 y male with a large left post-nasal space mass, a vascular mass involving the pituitary fossa.

?NBL (non-benign lesion)

?Sinonasal malignancy

?Pituitary Tumour

Laboratory Investigations

TSH 0.91 pmol/L (0.27-4.20)

Free T4 15.7 pmol/L (12-22)

FSH 0.8 IU/L ↓ (1.5-12.4)

LH 0.2 IU/L ↓ (1.7-8.6)

Testosterone 0.2 nmol/L ↓ (8.6-29.0)

PTH 1.7 pmol/L (1.6-6.9)

Prolactin measuring method:

The Elecsys prolactin sandwich immunoassay uses two monoclonal
antibodies directed against human prolactin.

R1 = biotinylated antibody – recognizes the N-terminal end of the
prolactin molecule

R2 – ruthenium complexed antibody probably reacts with a region in the
middle of the prolactin molecule.

1st incubation: a biotinylated monoclonal prolactin-specific
antibody and a monoclonal prolactin-specific antibody labeled with a ruthenium
complex form a sandwich complex.

2nd incubation: after addition of streptavidin-coated
microparticles, the complex becomes bound to the solid phase via interaction of
biotin and streptavidin.

Reaction mixture aspirated into the measuring cell where microparticles
are magnetically captured into the surface of the electrode.   Unbound substances are then removed with
ProCell. 

Application of a voltage to the electrode then induces
chemiluminescent emission which is measured by a photomultiplier, results
calculated by a standard curve.

Other Investigations

Monomeric prolactin – 7744 ug/L (70% recovery after PEG precipitation)

Biopsy: confirmed tumour stained strongly positive
with prolactin suggesting a prolactinoma.

Final Diagnosis

Pituitary Macroprolactinoma

Take Home Messages

Sandwich immunoassays are prone to high dose hook-effect. There are
various ways to overcome this effect. (This will later be expanded on – see AFP
/ Beta-HCG).

Prolactin appears in the serum as:

  1. Active monomeric
    prolactin (“little”) (80%) 23kDa
  2. Inactive dimeric
    prolactin (“big”) (5-20%) 50-60kDa
  3. Low activity
    tetrameric prolactin (“big-big”) (0.5-5%) 150-170kDa 

Precipitation by PEG yields the active monomeric
prolactin, expressed as a percentage recovery after precipitation.  Big-big prolactin consists of an
antigen-antibody complex of monomeric prolactin-immunoglobulin G and is defined
as macroprolactin.  This has a long
half-life in blood when compared to normal prolactin and gives false high
readings of prolactin, leading to unnecessary investigations in certain
cases.  A high prolactin should thus be
confirmed by doing a PEG precipitation.



Fluid Triglycerides

HOSP # WARD Surgical ICU
CONSULTANT   Dr. Heleen Vreede DOB/AGE 23y Female

Abnormal Result

Fluid triglycerides were requested on three samples, without any clinical information.

Presenting Complaint

The laboratory history was explored, to find that the patient had three subsequent samplings daily from a pleural fluid cavity.

History

A month prior to presentation, the patient had a breached stillbirth.

The following was found on Histology:

EPISODE NUMBER:
SA03381462
CLINICAL DETAILS:
23 year old female. G02 P2-1. VDRL: negative. Smoking: 8/day. Alcohol: none. HIV: negative. 750g breech stillbirth at 28/40.
MACROSCOPY:
The plate measures 130 x 100 x 30mm and weighs 196.8g.
The membranes are complete without evidence of meconium staining.
The cord measures 300mm in length with an average diameter of 15mm. Three umbilical vessels are identified with 3 twists per 100mm. The cord insertion is off-centre, 20mm from the plate margin.
Congested blood vessels are identified on examination of the foetal surface.
Cut-sections of the plate show:
- Retroplacental clot.
MICROSCOPY:
General:
Placental weight for gestational age is below the 10th percentile at 196.8g. Partial autolysis is present throughout the specimen.
The umbilical cord and membranes:
The umbilical cord contains two arteries and one vein. There is no evidence of vasculitis or funisitis. Wharton's jelly and membranes do not show meconium uptake. The amniocytes are intact and show no evidence of vacuolation or hyperplasia.
Chorionic plate:
The chorionic plate vessels are focally dilated. There is no evidence of chorioamnionitis.
Villi and intervillous spaces:
The stem villous vessels show partial obliteration as well as stromal sclerosis. Distal villous hypoplasia as well as accelerated villous maturation is seen. Intervillous thrombi are seen as well as intraparenchymal extension of the retroplacental haematoma. There is no evidence of infarction, villitis or intervillositis.
Maternal surface:
There is evidence of a large retroplacental haematoma. No chronic deciduitis or untransformed blood vessels are seen.
PATHOLOGICAL DIAGNOSIS:
Placenta, examination:
Maternal vascular malperfusion.
Retroplacental haematoma.
Reported by: Dr M Du Toit

Clinicians were indeed querying a chylothorax. A thoracic duct injury was suspected.

Examination

Unfortunately little clinical information is known, as can be seen above. The following table shows the clinical info which has been captured on the respective episodes’ request forms:

      Clinical history for episodes 
< SA03215505 >      ?UTI IN PREGNANCY
< SA03381462 > 03/10/2019     PLACENTA
< SA03466495 > 07/11/2019     MEDIASTINITIS
< SA03466500 > 08/11/2019     MEDIASTINITIS
< SA03466533 > 08/11/2019     MEDIASTINITIS
< SA03467168 > 08/11/2019     MEDIASTINITIS
< XC00366131 >      ILLEG
< SA03467081 >      ILLEGIBLE
< SA03469305 >      NECK ABSCESS
< SA03469995 >      ILLEGIBLE
< SA03472064 >      MEDIASITINITIS
< SA03470738 >      NECK ABSCESS
< SA03476491 >      PUS FLUID + MEDIASTINITIS
< SA03476496 >      PUS / FLUID + MEDIASTINITIS
< SA03476502 >      PUS / FLUID + MEDIASTINITIS
< SA03476507 >      PUS / FLUID + MEDIASTINITIS
< SA03489396 >      ?CHYLOTHORAX
< SA03485823 >      SEPSIS
< SA03491179 >      NECK ABSCESS
< SA03493180 >      Neck abscess with sepsis.
< SA03494446 >      CVC TIP
< SA03509355 >      LOOSE STOOLS
< SA03513657 >      THORACIC SURGERY
< SA03531013 >      MEDIASTINITIS

Laboratory Investigations

ChylothoraxDownload

Other Investigations

Final Diagnosis

A pleural fluid triglyceride >1.24 is suggestive of chylothorax.

The additional finding of a thin white layer present on the top of the sample after centrifugation indicates the presence of chylomicrons in the sample, which further supports the diagnosis of chylothorax.

Neck X-ray on 06/11/2019
Chest X-ray PA 06/11/2019
Chest X-ray lateral 06/11/2019
CT chest 11/11/2019
CT chest 11/11/2019
CT scan on 11 November 2019
Chest X-ray 12/11/2019
Chest X-ray 12/11/2019
Chest X-ray Mobile 14/11/2019

Take Home Messages

The primary role of the thoracic duct is to carry 60 – 70% of ingested fat at a concentration of 0.4 – 6 g/dl from the intestine to the circulatory system.

  • Chyle contains large amounts of cholesterol, triglycerides, chylomicrons and fat soluble vitamins.
  • Lymph is the other main constituent of chyle and is made up of
    • immunoglobulins
    • enzymes
    • between 400 and 6800 white blood cells/ml, the majority of which are lymphocytes.
  • Chyle transportation is maximal after a high fat meal and minimal with starvation where flow is reduced to almost a trickle.

Classically, a chyloma, a collection of chyle below the pleura develops when the thoracic duct first leaks. Although rarely detected, it manifests itself as a swelling in the supraclavicular fossa which may be associated with severe chest pain, dyspnoea and tachycardia.

Chylomas can also manifest themselves at other sites of the pleura without causing supraclavicular swelling. Eventually the chyloma bursts through the pleura where the chyle accumulates in the pleural space.

Very rarely, the chyle leak may lead to chylomediastinum or chylopericardium.

Chylothorax-aetiology-diagnosis-and-Rx-Mcgrath-2010Download

Roughly 2.4 l of chyle is transported through the lymphatic system every day.

Damage to, or rupture of the thoracic duct can give rise to a large and rapid accumulation of fluid in the pleural space.

Causes of chylothorax can be classified as follows:

The theorized causes of chylothorax in this case could be one of the following:

  1. The breached stillbirth a month prior to presentation could have caused rupture of the thoracic duct due to increased pressure due to extreme valsalva. Could this be dormant for 1 month and then present with the neck abscess with an anaerobic infection? Could anaerobic bacterial transmission from the gut into a chylous cyst in the neck be the cause? It is however unlikely that delivery of a 750g fetus causes that much trauma.
  2. Iatrogenic chylothorax due to the thoracic surgery.
  3. Left-sided placement of a Central Venous Catheter during delivery of the stillbirth, which accidentally damaged the thoracic duct. The placement of the CVP could also have caused a pneumothorax with subsequent stretching and damage to the thoracic duct.

Remember Chylomicrons float!

DISORDERS OF LIPOPROTEIN METABOLISM - DISORDERS OF THE VASCULATURE ...


ACTH

HOSP # WARD G16 Medical Ward
CONSULTANT   DOB/AGE 54 y Female

Abnormal Result

21/08/2018 Two ACTH tests (referred to another laboratory) and two
Cortisol levels (at our laboratory) were done. 
At first it was thought to be a dexamethasone suppression test, but then
realized the clinicians were suspecting hypopituitarism.

10h05: ACTH 0.7 pmol/L ↓ (1.6-13.9)  Cortisol  8 nmol/L ↓  (Morning: 133- 537; Afternoon 68 – 327)

10h35: ACTH 1.8 pmol/L N (1.6-13.9) 
Cortisol  68 nmol/L ↓  (Morning: 133- 537; Afternoon 68 – 327)

Presenting Complaint

? hypopituitarism

History

Known with a pituitary macroadenoma, previously seen at the Radiotherapy clinic in 2016.

Examination

No clinical info available.

For Primary adrenal insufficiency one would expect: Hyperpigmentation
(due to ↑ ACTH), +/- hyperkalemia/hyponatremia (aldosterone effect), +/-
virilization.

For Secondary adrenal insufficiency there is subtle symptoms, electrolytes are not deranged significantly because aldosterone function is preserved. See table on Bishop 7th ed. p. 459.

Laboratory Investigations

Measurement of
plasma ACTH concentration is used to assess Cushing’s disease, adrenal tumors,
ectopic ACTH-producing tumors, Addison’s disease, Nelson’s syndrome, and
hypopituitarism.

The
laboratory diagnosis of hypopituitarism, however is relatively straightforward.
In contrast to the primary failure of an endocrine gland that is accompanied by
dramatic increases in circulating levels of the corresponding pituitary tropic
hormone, secondary failure (hypopituitarism) is associated with low or normal
levels of tropic hormone.  This is the
diagnosis in this case with the history of previous radiotherapy which was
given for a macro-adenoma.

Other Investigations

Free T4 on 19/04/2018 was 7.8 pmol/L (12-22), also suggesting possible hypopituitarism, although a TSH would be helpful.

Final Diagnosis

Hypopituitarism confirmed.

Take Home Messages

Dexamethasone suppression test need only measurement of cortisol, not accompanying ACTH, except in extended work-up however, where a Cosyntropin (CRH) stimulation test can be done to distinguish between pituitary or hypothalamic insufficiency.

Evaluation of pituitary function need the Primary hormone (Cortisol) as well as the tropic hormones from the pituitary (ACTH).



Paracetamol Overdose

HOSP # WARD C15 Casualties
Consultant   DOB/AGE 33 year Female

Abnormal result

Paracetamol 25ug/ml (163 umol/L)     Serum osmolarity 310mmol/L

Presenting Complaints

Brought to casualties with stupor from Mitchells Plein Hospital.

History

33 y female presented with stupor after ingestion of an unknown amount of pills.  Empty container of Amitriptiline and Paracetamol was found with her.

Examination

Non-specific neurologic signs, but delirium present. Patient did have an episode of vomiting.  No pathological signs on abdominal examination.

Laboratory Investigations

12/08/2018: Na 156 mmol/L (H)         Urea 4.2mmol/L       Tot. Bili 4 umol/L K 1.9 mmol/L (L)             Creat 88 umol/L       ALT 82 U/L Cl 97.9 mmol/L (L)          Gluc 3.52 mmol/L     AST 238 U/L                  Ammonia 35 umol/L Bicarb 16.6 mmol/L (L)    Osmol 310 mmol/L (H)        Osmolar gap: -10 mM    Anion Gap: 47 mmol/L    

Marked elevation of hepatocellular enzymes, ductal enzymes within normal range.  Within the course of three days the patient developed Klebsiella Pneumoniae on intubation in ICU with DIC and marked renal failure (Creat 506, Urea 26.8) and demised in ICU 3 days after admission, although liver enzymes were not markedly more deranged as initial presentation.  

Paracetamol: The Paracetamol level was never repeated after admission.  Doing an in-house experiment with calibrator and spiking the calibrator samples with N-acetylcysteine correlating with therapeutic plasma levels, I demonstrated that our method on the Roche analyzer, with the enzymatic assay, causes a clinically significant negative interference in the measured paracetamol.                                                                 

The enzymatic assay principle:

arylacylamidase hydrolysis                       o-cresal + periodate catalyst

Acetaminophen→     p-aminophenol+acetate →    indophenol (measured @600nm)

Other Investigations

Tricyclic antidepressant levels 58 ug/L ([TCA] in overdose patients range from 29-1732ug/L, but has not been found to correlate to clinical outcome, unless plasma level is more than 1000ug/L).

Final Diagnosis

Klebsiella Sepsis (confirmed on blood culture 1 day after death) DIC with marked renal failure.

Take Home Messages

  • Paracetamol reporting units must be confirmed, we generally use ug/ml, but it has created confusion previously, as nomograms used in South Africa generally use ug/ml.
  • N-acetyl cysteine may cause negative interference with the measurement of paracetamol in the enzymatic assay.  Sampling for Paracetamol levels should thus be done before an IV dose of NAC is given to eliminate this possible error.  National guidelines with toxicology will likely be amended.