Use of Blood Chemistry for Diagnosis of Neurological Disease Flashcards
1
Q
Synaptic transmission
- Synaptic … effectively essentially chemical release between nerve and end organ
- Neurotransmitters are defined partly as being released into a synapse (therefore never really …)
- However there is adaptation of postganglionic neurones in some organs/cells to release these compounds systemically e.g. adrenaline from the adrenal medulla
- … – refers to endocrine system that is under neuronal control
A
- Synaptic transmission effectively essentially chemical release between nerve and end organ
- Neurotransmitters are defined partly as being released into a synapse (therefore never really measured)
- However there is adaptation of postganglionic neurones in some organs/cells to release these compounds systemically e.g. adrenaline from the adrenal medulla
- Neuroendocrine – refers to endocrine system that is under neuronal control
2
Q
A 42 y woman - Presents with episodes of diarrhoea
What advice is given?
A
- She is given dietary advice - For at least 4 days before and also during the24h collection period she avoids eating the following foods:
- Walnuts, Chocolate
- Tomatoes, Aubergines, Avocado
- Plums, Bananas, Kiwi Fruit, Pineapple
- These foods are rich in 5-HIAA precursors
- She has diagnostic imaging investigations
- These are specialist investigations that often include somatostatin receptor scintography using a compound that binds to somatostatin receptors on carcinoid tumours. This will not only locate the tumour but also the presence of hepatic metastases.
The primary tumour is removed at surgery and liver metastases treated by embolisation.
3
Q
Synaptic transmission - Neuroendocrine
- Examples:
- … (lung and gut; carcinoid tumours – urinary 5-hydroxy-indole acetic acid (5HIAA))
- Plasma … A (present in any cell with secretory vesicles, used as tumour marker)
- … (adrenal medulla; sympathetic)
- … and … (posterior pituitary – … not really measured, - serum copeptin cleavage product of … can be measured)
- Serum … (medullary C cells of thyroid, tumour marker)
A
- Examples:
- Serotonin (lung and gut; carcinoid tumours – urinary 5-hydroxy-indole acetic acid (5HIAA))
- Plasma Chromogranin A (present in any cell with secretory vesicles, used as tumour marker)
- Adrenaline (adrenal medulla; sympathetic)
- Oxytocin and ADH (posterior pituitary – oxytocin not really measured, - serum copeptin cleavage product of ADH can be measured)
- Serum Calcitonin (medullary C cells of thyroid, tumour marker)
4
Q
Hypothalamus-pituitary axis
A
5
Q
Endocrine circadian rhythms
- Circadian rhythm of pituitary hormones is controlled by the supraoptic nucleus.
- In addition many show pulsatile secretion especially GH, TSH.
- For example serum … concentrations:
- 6-10 am 133 - 537 nmol/L
- 4-8 pm 68 - 327 nmol/L
- This is driven by plasma … concentrations:
- 9 am <50 ng/L
- Midnight <10 ng/L
A
- Circadian rhythm of pituitary hormones is controlled by the supraoptic nucleus.
- In addition many show pulsatile secretion especially GH, TSH.
- For example serum cortisol concentrations:
- 6-10 am 133 - 537 nmol/L
- 4-8 pm 68 - 327 nmol/L
- This is driven by plasma ACTH concentrations:
- 9 am <50 ng/L
- Midnight <10 ng/L
6
Q
Neural Tube Defects
- Birth defect: opening in spinal cord or brain
- Early in human development
- Multifactorial: genes, environment plus folate deficiency, maternal T1DM and use of certain anticonvulsants
- Screening:
- Maternal serum alpha-…
- fetal …
A
- Birth defect: opening in spinal cord or brain
- Early in human development
- Multifactorial: genes, environment plus folate deficiency, maternal T1DM and use of certain anticonvulsants
- Screening:
- Maternal serum alpha-fetoprotein
- Fetal ultrasound
7
Q
AFP ⍺- fetoprotein
- Structurally & functionally similar to albumin
- Produced by fetal liver & yolk sac
- Most … protein in fetal serum
- … in fetus with … in serum albumin
- Onco-fetal Ag, marker of new hepatocytes:
- Liver regeneration
- Hepatocellular carcinoma
A
- Structurally & functionally similar to albumin
- Produced by fetal liver & yolk sac
- Most abundant protein in fetal serum
- Declines in fetus with rise in serum albumin
- Onco-fetal Ag, marker of new hepatocytes:
- Liver regeneration
- Hepatocellular carcinoma
8
Q
Maternal serum AFP
A
9
Q
Maternal serum AFP (MoM)
A
10
Q
Serum AFP levels – through life and other causes
A
11
Q
Physiology of Neurons: Electrochemical properties
- Synaptic transmission: is dependent on potential … and therefore change in electrochemical milieu affects … for excitement.
- Changes in ion concentration can lead to … and other neurological sequelae e.g. hyperventilation and refeeding syndrome.
A
- Synaptic transmission: is dependent on potential difference and therefore change in electrochemical milieu affects threshold for excitement.
- Changes in ion concentration can lead to paraesthesia and other neurological sequelae e.g. hyperventilation and refeeding syndrome.
12
Q
Ions influencing neural transmission
A
13
Q
Case - A 17 year old woman has a tight feeling in her chest and has felt short of breath for the past two hours. She also has tingling in her fingers
A
- Hyperventilation – you blow off CO2 so end up blowing off respiratory acid causing a respiratory alkalosis. Albumin is negatively charged and binds positive ions. If lose hydrogen ions you free up some more negative sites so the calcium that was previously free is now able to bind them so the ‘free calcium’ drops. This directly causes nerves to fire off spontaneously and accounts for the paraesthesia in hyperventilation e.g. lip tingling…..
14
Q
Forms of Serum Calcium
A
15
Q
Re-feeding Syndrome
- Definition: severe … and … shifts and related metabolic implications in … patients undergoing re-feeding
- Especially prevalent in severely …
- Usually occurs during the first few … after initiating re-feeding
- Observed both with … and … routes
- Example of how low electrolytes can effect physiology of contractile and neurological tissues…
A
- Definition: severe fluid and electrolyte shifts and related metabolic implications in malnourished patients undergoing re-feeding
- Especially prevalent in severely malnourished
- Usually occurs during the first few days after initiating re-feeding
- Observed both with enteral and parenteral routes
- Example of how low electrolytes can effect physiology of contractile and neurological tissues…
16
Q
Re-feeding Syndrome
- Definition…
A
- Definition: severe fluid and electrolyte shifts and related metabolic implications in malnourished patients undergoing re-feeding
- Especially prevalent in severely malnourished
- Usually occurs during the first few days after initiating re-feeding
- Observed both with enteral and parenteral routes
- Example of how low electrolytes can effect physiology of contractile and neurological tissues…
17
Q
Peripheral Neuropathy
- Single nerve - …
- Two or more nerves in different areas - … mononeuropathy
- Many or most of the nerves are affected – …
- … nerves - movement of all muscles under conscious control
- … nerves - feeling of a light touch, temperature or pain.
- Autonomic nerves - control organs to regulate activities that people do not control consciously
A
- Single nerve - mononeuropathy
- Two or more nerves in different areas - multiple mononeuropathy
- Many or most of the nerves are affected – polyneuropathy
- Motor nerves - movement of all muscles under conscious control
- Sensory nerves - feeling of a light touch, temperature or pain.
- Autonomic nerves - control organs to regulate activities that people do not control consciously
18
Q
Laboratory role in peripheral neuropathy
- … – commonest cause
- Systemic autoimmune disease – Sjogren’s syndrome, systemic lupus, rheumatoid arthritis
- End stage CKD – dialysis
- Nutritional – vitamin B12, thiamine, pyridoxine
- Paraneoplastic – immune changes linked to tumours
- Paraproteinaemia – multiple myeloma
- Chemotherapy – drug monitoring
- Infective – various viruses – varicella zoster, herpes simplex
- Genetic – acute intermittent porphyria, Refsum’s disease, Fabry disease
A
- Diabetes – commonest cause
- Systemic autoimmune disease – Sjogren’s syndrome, systemic lupus, rheumatoid arthritis
- End stage CKD – dialysis
- Nutritional – vitamin B12, thiamine, pyridoxine
- Paraneoplastic – immune changes linked to tumours
- Paraproteinaemia – multiple myeloma
- Chemotherapy – drug monitoring
- Infective – various viruses – varicella zoster, herpes simplex
- Genetic – acute intermittent porphyria, Refsum’s disease, Fabry disease
19
Q
Case - A 32 year old man :
- Complains of unsteadiness while walking, “pins and needles” sensation in his hands and feet, and weakness in his legs. This had started about two weeks ago and had progressively worsened.
- Neurological examination showed an ataxic gait, impaired sensation to light touch in his hands and feet, with impaired vibration, proprioception. His leg reflexes were diminished.
- There was no history indicating diabetes, viral infection or auto-immune disorder.
A
- However -
- Neuropathy due to B12 deficiency is more commonly seen in much older people associated with macrocytic anaemia.
- This is usually due to antibodies to gastric parietal cells and intrinsic factor.
- Intrinsic factor is essential to the binding of ingested B12 and its uptake by enterocytes in the terminal ileum.
- Also diseases of the terminal ileum eg Crohn’s disease
20
Q
Meninges - Meningitis
- Meninges cover the brain and spinal cord
- …: headache, neck stiffness and photophobia often with nausea and vomiting.
- It is due to … of the meninges e.g. infection or blood.
- Blood in CSF (from SAH or traumatic tap) will show up as … on spectrophotometry, if blood present in vivo it is metabolised to bilirubin, also measured by scan.
A
- Meninges cover the brain and spinal cord
- Meningism: headache, neck stiffness and photophobia often with nausea and vomiting.
- It is due to inflammation of the meninges e.g. infection or blood.
- Blood in CSF (from SAH or traumatic tap) will show up as oxyhaemoglobin on spectrophotometry, if blood present in vivo it is metabolised to bilirubin, also measured by scan.
21
Q
Cerebrospinal fluid (CSF)
- Obtained by spinal …:
- Common requirements (clearly label in order of draw):
- -1st - White top universal specimen bottle for micro (10 drops)
- -2rd - White top universal specimen bottle for biochemistry (20 drops)
- -3rd - Additional white top bottle for micro to ensure cell count decreasing (10 drops)
- -Paired blood sample for glucose (normal CSF:serum ratio 0.6), protein, bilirubin, and (rarely) lactate and oligoclonal bands.
A
- Obtained by spinal tap:
- Common requirements (clearly label in order of draw):
- -1st - White top universal specimen bottle for micro (10 drops)
- -2rd - White top universal specimen bottle for biochemistry (20 drops)
- -3rd - Additional white top bottle for micro to ensure cell count decreasing (10 drops)
- -Paired blood sample for glucose (normal CSF:serum ratio 0.6), protein, bilirubin, and (rarely) lactate and oligoclonal bands.
22
Q
Subarachnoid Haemorrhage - Stroke
- Types of stroke
- … – commonest type 85%
- Haemorrhagic – 15%
- … – 10%
- Subarachnoid haemorrhage – 5%
- Transient … attack
A
- Types of stroke
- Ischaemic – commonest type 85%
- Haemorrhagic – 15%
- Intracerebral – 10%
- Subarachnoid haemorrhage – 5%
- Transient ischaemic attacl
23
Q
Subarachnoid Haemorrhage - Stroke
- Types of stroke
- Ischaemic – commonest type …%
- Haemorrhagic – …%
- Intracerebral – …%
- Subarachnoid haemorrhage – …%
- Transient ischaemic attacl
A
- Types of stroke
- Ischaemic – commonest type 85%
- Haemorrhagic – 15%
- Intracerebral – 10%
- Subarachnoid haemorrhage – 5%
- Transient ischaemic attacl
24
Q
Case - A 36 year old man
- Is brought to ED by ambulance having collapsed while walking to his local coffee shop. He described having a severe sudden headache – like being hit on the head by a hammer.
- On arrival he was rather confused GCS 13 (E3V4M6). BP 150/70. Respiratory rate 20/min. Oxygen saturation 96%. Limb movements were equal and good strength. Pupils were equal and reacting to light.
- CT scan revealed no abnormality and a lumbar puncture was undertaken 6 h after the collapse time.
A
25
Q
… aneurysm causing SAH
A
Berry aneurysm causing SAH
26
Q
Case - A 21-year-old man presented to ED
- He complained of headache, dizziness, mild photophobia and fever for one day. He had vomited three times. His BP was 109/50, pulse 115 bpm, temperature 38.1°C. He was fully conscious and clinically stable.
- Physical examination showed that there were generalised maculo-papular rash that did not blanch on pressure from a glass. In addition there was a patch of purpura on the dorsum of his right hand. There was mild neck rigidity. Chest, cardiac and abdominal examination did not reveal any abnormality.
A
27
Q
CSF in different causes of
meningitis
A
28
Q
Case - A 32 year old woman
- Presents with leg weakness causing her to stumble occasionally. She has noticed a tingling sensation in her lower leg and on questioning agrees she has had episodes of visual disturbance.
- She recalls having similar problems after the delivery of her son 2 years previously.
- Following neurological examination she has an MRI scan.
A
ms
29
Q
CSF – Oligoclonal banding
A
31
Q
Routine laboratory investigations in dementia (<1% are reversible)
A
33
Q
Altered Consciousness – AEIOU TIPS
A
34
Q
Case - A 40 year old man
- Suffers a gripping chest pain and collapses at home. His wife calls for an ambulance – paramedics start resuscitation and demonstrate ischaemic changes on his ECG.
- On admission to the Emergency Department he is in sinus rhythm but remains rather comatose.
- There is a suspicion this may be due to cerebral …
A
- Suffers a gripping chest pain and collapses at home. His wife calls for an ambulance – paramedics start resuscitation and demonstrate ischaemic changes on his ECG.
- On admission to the Emergency Department he is in sinus rhythm but remains rather comatose.
- There is a suspicion this may be due to cerebral hypoxia.
43
Q
Inborn Errors of Metabolism causing Brain Disorders - >1100 described
A
45
Q
Approaches to Treatment of IEMs
A
47
Q
Drugs used in Neurological Conditions
A
48
Q
Role of the Laboratory in Drug Monitoring
A
49
Q
Phenytoin
- Used in the treatment of …
- Variable absorption from the …
- Metabolism by cytochrome enzymes – genetic variation
- Largely bound to … in the circulation
- Free unbound phenytoin is the … form of the drug
- Target therapeutic range 10-20 mg/L (bound plus free forms)
- ‘Free’ phenytoin target range 1-2.5 mg/L
A
- Used in the treatment of epilepsy
- Variable absorption from the gut
- Metabolism by cytochrome enzymes – genetic variation
- Largely bound to albumin in the circulation
- Free unbound phenytoin is the active form of the drug
- Target therapeutic range 10-20 mg/L (bound plus free forms)
- ‘Free’ phenytoin target range 1-2.5 mg/L
51
Q
Dose concentration relationship for phenytoin
A
52
Q
Case - An 17 year old male
- He has epilepsy and takes phenytoin by mouth 200 mg twice daily to control his seizures.
- He has recently noted difficulty in climbing stairs.
- On examination he has a broad gait and muscle power 3/5 in hip extensors and flexors.
- interpretation?
A
- Interpretation:
- Effect of phenytoin on Vitamin D metabolism
- Normal Vit D metabolism:
- Vit D whether formed in the skin or ingested is activated by 25-hydroxylation in the liver prior to 1-hydroxylation in the kidney to form 1,25-OH Vit D.
- This form enhances calcium absorption from the gut.
- Phenytoin:
- Activates enzymes that inactivate Vit D leading to decreased calcium absorption. The resulting lack of calcium promotes parathormone secretion to enhance calcium release from bone.
53
Q
Case - A 33 year old woman
- Presents with oligomenorrhoea and more recently galactorrhoea.
- She has a history of schizophrenia that is treated with risperidone (an anti-psychotic drug).
A
- Dopamine usually prevents release of prolactin
- So, it is due to risperidone - Risperidone is a dopamine receptor blocker.
- The prolactin secreting cells in the anterior pituitary are under inhibitory secretion control by dopamine.
- When a dopamine receptor blocker binds to the dopamine receptors in the anterior pituitary, it releases the prolactin secreting cells from the inhibition by dopamine.
- Hence serum prolactin concentrations are increased
- All patients starting antipsychotics should have a prolactin measured before starting to avoid an MRI later.
55
Q
Consequences of hyperprolactinaemia
A
56
Q
Drugs causing hyperprolactinaemia
A
59
Q
Monitoring lithium therapy
A
60
Q
Drug-induced hyponatraemia
A
61
Q
Drug induced hypogonadism
A
62
Q
Pseudocholinesterase deficiency (suxamethonium apnoea)
A
63
Q
Pseudocholinesterase deficiency (suxamethonium apnoea) - tests
A
