CPATH

Question 1

Jason is a 4 y/o who complains of a worsening headache over the course of 2 days. His mother had been treating him with pain syrup but started worrying when he developed a fever, refused to eat and wanted to sleep all the time. She took him to Red Cross Hospital where the paediatrician found that Jason had neck stiffness and signs of raised intracranial pressure. He immediately suspected meningitis and started Jason on antibiotics. Blood cultures and further tests were done to identify the causative organism.

Describe the cerebrospinal fluid (CSF) findings if one had been done, given that bacterial meningitis is suspected (2)

Answer 1

Appearance turbid, Glucose, Protein, White cells  raised neutrophils

Question 2

State the most common endocrine disorder complicating meningococcal meningitis (1)

Answer 2

Adrenal failure (Waterhouse-Friederichson syndrome) (1)

Question 3

Describe how you would suspect this disorder (Q.26) clinically, and how you would confirm it biochemically (2½)

Answer 3

• Profound shock/ circulatory collapse (1)

- Hypoglycaemia, hyperkalaemia, hyponatraemia, acidosis (1 ½) (also accept low cortisol, low aldosterone, high renin)

Question 4

A patient in the medical ward has been diagnosed with bacterial meningitis. His blood glucose is found to be 10mmol/l. What approximate value would you expect his CSF glucose to be: (2)

A: before treatment is initiated?
B: after full recovery? (Assuming his blood glucose remains at 10mmol/l)

Answer 4

Less than 6 mmol/l or less than 60% of blood glucose (1)

6-8mmol/l or 60-80% blood glucose (1)

Question 5

Name two biochemical tests commonly performed on CSF when meningitis is suspected and state how the results change in bacterial meningitis (2)

Answer 5

Glucose (goes down, often to zero), Protein (increases many fold)

Question 6

Briefly explain why CSF chloride levels are typically lower in patients with tuberculous meningitis (1)

Answer 6

In TBM, protein levels in CSF increase dramatically and chloride levels therefore decrease to maintain electroneutrality.

Question 7

List of diagnoses: SAH (Subarachnoid haemorrhage), Multiple Sclerosis, Normal CSF, TB meningitis, Viral meningitis, Fungal meningitis, Bacterial meningitis, Hypoglycaemia

A: Low chloride, ++ protein, glucose
B: Xanthochromia 
C: Oligoclonal banding 

Answer 7

A: TB meningitis (1)
B: SAH (1)
C: Multiple Sclerosis (1)

Question 8

Briefly explain why the CSF glucose needs to be interpreted with a plasma glucose measurement (2)

Answer 8

CSF glucose is in equilibrium with blood glucose concentration [1] over the past 4 hours [½]; interpretation therefore requires knowledge of concurrent blood glucose [½].

Question 9

Name one test used to evaluate blood-brain barrier permeability [1]

Answer 9

CSF:plasma albumin ratio; or IgG index

Question 10

List four (4) biochemical abnormalities that occur in tumour lysis syndrome [2]

Answer 10

Hyperphosphataemia, Hyperkalaemia, Hyperuricaemia, Hypocalaemia, Metabolic acidosis

Question 11

Chloride concentration in cerebrospinal fluid (CSF) is normally higher than in plasma. Outline the reason for this (2)

Answer 11

CSF has a much lower negatively charged protein content than plasma, so to maintain electroneutrality, chloride increases.

Question 12

State why the CSF protein concentration is higher in the lumbar region than in the ventricles (2)

Answer 12

Due to higher hydrostatic pressures lower down in the subarachnoid space, water is forced out into the intersttitial space until the colloid osmotic pressure (and protein concentration) of the CSF increases to a point that an equilibrium is reached. Lower down, CSF circulation is slower, allowing more time for equilibration with plasma proteins

Question 13

Define the IgG index (1)

Answer 13

IgG index = (IgGCSF/ AlbuminCSF)/(IgGserum/Albuminserum)

Question 14

State what a raised IgG index implies (1)

Answer 14

Increased local (intrathecal) production of IgG

Question 15

List two (2) causes of a raised IgG index (1)

Answer 15

Neurosyphilis, multiple sclerosis

Question 16

In a patient with a raised total CSF protein, state the significance of an increased IgG/albumin ratio in CSF, particularly if this ratio in plasma is normal (2)

Answer 16

Local IgG production due to an infective or autoimmune process within the CNS, rather than a non-specific increase in blood-brain barrier permeability.

Question 17

Indicate the significance of a very high (rather than low) CSF glucose in a comatose patient (1)

Answer 17

Reason for the coma is uncontrolled diabetes rather than meningitis.

Question 18

In a patient with a high total CSF protein, describe how you would distinguish increased protein permeability of the blood/brain barrier from antibody production within the CNS (such as may occur in neurosyphilis or multiple sclerosis) (2)

Answer 18

By examining the ratio of CSF IgG to albumin, or ideally, by dividing the CSF IgG/albumin ratio by the serum IgG/albumin ratio. The value for increased permeability is <0.7, while for local IgG production it is >0.7.

Question 19

Name two (2) causes for a bloodstained CSF, and suggest two (2) ways by which they can be differentiated, explaining how the responses differ in each case (6)

Answer 19

Subarachnoid haemorrhage (SA), bloody tap (BT). By collecting sequential samples (clears in BT, remains uniformly bloodstained in SA). By spinning down and observing supernatant (clear in BT, possibly xanthochromic in SA).

Question 20

Explain why chloride is normally higher in CSF than in serum (2)

Answer 20

Molar concentration of protein is much lower in CSF than in serum. To maintain electroneutrality chloride (negatively charged) is higher.

Question 21

List two (2) analytes that are used to determine blood brain barrier permeability (1)

Answer 21

Albumin and Immunoglobulin

Question 22

Name a chemical analyte measured in CSF (not provided in this case) which can be useful in the diagnosis of bacterial meningitis (½)

Answer 22

Lactate

Question 23

List three (3) causes for a massively elevated CSF protein (e.g. 10g/L) (1½)

Answer 23

Obstruction of CSF flow in the spine (Froin Syndrome): Tumour, Abscess, Disc prolapse

Question 24

Explain how Froin’s syndrome (spinal block) can affect CSF protein levels (2)

Answer 24

Failure of CSF to circulate extends its residence time and allows time for proteins to leak across from blood into CSF. This can result in extremely high CSF protein concentration

Question 25

Explain the significance of disproportionate increase in CSF IgG relative to albumin (a CSF IgG index >1), and give an example of a disorder in which this is found (2)

Answer 25

Indicates local production of IgG within the CNS, rather than simple diffusion of protein from the plasma due to meningeal inflammation. Examples include neurosyphilis or multiple sclerosis.

Question 26

Explain why chloride concentration is significantly higher, and calcium is lower, in CSF compared to plasma (1)

Answer 26

Protein (albumin) that carries negative charge and binds calcium, is essentially absent from CSF. The chloride makes up the negative charge in the CSF

Question 27

If there is a complete pathological spinal block, what is the major difference in composition of CSF proximal and distal (cephalic and caudal) to the spinal block (1)

Answer 27

Much higher protein level proximally.

Question 28

What is the predominant protein in normal CSF? (½)

Answer 28

Albumin

Question 29

What is the term ‘xanthochromia’, as applied to CSF? (1) What is its significance? (1) What chemical substance is responsible for this condition? (½) (1x1x ½ = 2½)

Answer 29

Yellow discoloration of CSF; indicates old bleed into subarachnoid space; Bilirubin from haem breakdown

Question 30

A patient presents with a spinal blockage due to a lesion at T10. Describe the difference in the protein concentration (if at all) in CSF taken above and below the site of the block (1)

Answer 30

Protein concentration above the lesion is normal. Protein concentration below the lesion is massively elevated (Froin syndrome). (Due to lack of CSF circulation below the lesion)

Question 31

Describe the macroscopic appearance of normal CSF (½)

Answer 31

Crystal clear (like water)

Question 32

Define ‘xanthochromia’ of CSF. Give two causes of xanthochromia (1.5)

Answer 32

• Yellow discoloration of CSF

- Old bleed OR high protein – e.g. TBM, spinal block (Froin’s Syndrome)

Question 33

“When performing a LP, what is the macroscopic appearance of the CSF in a SAH and how would you differentiate this from a “bloody tap?” (2)

Answer 33

Bloodstained CSF. Does not clear progressively as CSF is allowed to flow.
If it is a recent sah the tap would be blood stained and if it is more than 72? hrs old it would be yellow (xanthochromia). You can distinguish between the two as a bloody tap will clear after the first tube is full whereas sah won’t clear.

Question 34

What is the typical CSF finding in an ‘old’ subarachnoid haemorrhage (approximately 3 days later)? What is it due to? (2)

Answer 34

Xanthochromia (yellow CSF). Bilirubin from haem breakdown.
It would be yellow stained (xanthochromia) this is due to the break down products of haemoglobin from the rbcs that have entered the csf. (bilirubin)