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202: Theme 1 > Clinical Biochemistry of Neurological diseases > Flashcards

Clinical Biochemistry of Neurological diseases Flashcards

1
Q

What neuroendocrine systems are there?

A
  • 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 a 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
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2
Q

What is 5-HIAA and what foods are rich in this?

A
  • it’s a metabolite of serotonin
  • Walnuts, chocolate, Tomatoes, Aubergines, Avocado, Plums Bananas, Kiwi, Pineapple- are rich in 5-HIAA precursors
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3
Q

Describe the key aspects of the Hypothalamus-pituitary axis

A
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4
Q

Give an overview of endocrine circadian rhythms

A
  • circadian rhythms of the pituitary hormones is controlled by the supraoptic nucleus
  • many cell groups show pulsatile secretions of GH and TSH
    • serum cortisol conc. are higher in the morning
    • this is driven by plasma ACTH (Adrenocorticotropic hormone) conc.
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5
Q

Neural tube defects

  • defect and causes
A
  • opening in the spinal cord or brain
  • genes, environment + folate deficiency, maternal T1DM, use of certain anticonvulsants

Screening:

  • Maternal serum alpha-fetoprotein
  • Fetal ultrasound
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6
Q

give an overview of Alpha- Fetoprotein

A
  • protein that is structurally similar to albumin produced the fetal liver & yolk sac
  • declines in fetus with rise in serum albumin
    • peaks between week 10-20 of gestation then decrease gradually
    • maternal serum AFP gradually increases through pregnancy peaks between week 28-36 then slightly decreases
  • Onco-fetal Ag, is a marker of new hepatocytes:
    • liver regeneration
    • Hepatocellular carcinoma
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7
Q

What are the key points that serum AFP levels change throughout life?

A
  • Embryonal and early postnatal life
  • liver generation
  • hepatocellular carcinoma
  • Tertocarcinoma
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8
Q

What is the impact of ion conc. on neurological function?

A
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9
Q

What forms of Serum Calcium are there?

A
  • Total serum calcium: 2.20-2.55mmol/L
  • Albumin bound: 45%
  • Complexed: 5%
  • Ionised (active, pH dependent 7.40): 50% - 1.15-1.35mmol/L
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10
Q

Explain how hyperventilation causes hypocalcaemia

A
  • hyperventilation causes respiratory alkalosis as CO2 is excreted
  • this results in loss of H+ ions which makes the albumin more negatively charged
  • Ca2+ is then able to bind to the now -ve albumin
  • this reduces the free calcium in serum
    • causes nerves to spontaneously fire off and accounts for paraesthesia in hyperventilation
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11
Q

What are the effects of Nitrous oxide (whippits) use?

A
  • results in subacute combined degeneration of the spinal cord and peripheral neuropathy
    • converts B12 from active monovalent form to an inactive bivalent form
  • Active B12 is a coenzyme for methionine synthase
    • important for the generation of methyl groups for DNA RNA and myelin
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12
Q

Neuropathies caused by B12 deficiency

A
  • B12 deficiency usually seen in older people due to macrocytic anaemia
    • due to antibodies to gastric parietal cells and intrinsic factor
    • intrinsic factor needed for the binding of ingested B12
  • Diseases of the terminal ileum: Cohn’s disease
  • Use of Nitrous Oxide (whippits)
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13
Q

Meningitis

A
  • Meningism causes: headache, neck stiffness and photophobia often with N&V
  • Inflammation of meninges due to infection or blood
    • Blood in the CSF will show up as oxyhaemoglobin on spectrophotometry
    • if blood is in vivo it is metabolised to bilirubin - measured by the scan
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14
Q

Explain how CSF is collected

  • different sample types
A
  • obtained by a spinal tap
  • 1st - Whitetop 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)
  • can be done as a blood sample for glucose, protein, bilirubin, and rarely lactate and oligoclonal bands
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15
Q

TYpes of subarachnoid Haemorrhage - Stroke

A
  • Ischaemic (most common - 85%)
  • Haemorrhagic - 15%
    • Intracerebral - 10%
    • Subarachnoid haemorrhage - 5%
  • Transient ischaemic attack
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16
Q

Review the pathway for examining bilirubin absorbance in CSF for detection of intracranial bleed

A
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17
Q

What is this an image of?

A

Berry aneurysm causing SAH

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18
Q

How does the CSF present in different causes of meningitis

A
  • Bacterial meningitis
  • Viral meningitis
  • Fungal Meningitis
  • Tuberculous Meningitis
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19
Q

What is Oligoclonal banding?

A
  • bands of immunoglobulins that are seen when a patient’s blood serum or cerebrospinal fluid (CSF) is analyzed. They are used in the diagnosis of various neurological and blood diseases, especially in multiple sclerosis
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20
Q

What is the CSF like in Alzheimer’s disease?

A
  • high concentrations of a hyperphosphorylated form of tau protein
  • the hyperphosphorylation of tau cause it to lose its ability to bind to the microtubules and to stimulate their assembly
  • leading to neuronal damage and the increased conc. in the CSF
  • there are increased amounts of neuritic plaques and neurofibrillary tangles seen in neurons and their synapses
    • these plaques are amyloid-Beta depositions leading to lower conc.s of this in the CSF
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21
Q

What routine laboratory investigations are done in dementia

A
  • Full blood count and ESR – vasculitis, anaemia
  • Calcium – hyper/hypocalcaemia
  • Folate and vitamin B12
  • HbA1c - diabetes
  • Liver function tests – liver failure
  • Sodium, potassium, creatinine – CKD, electrolyte disorders
  • Thyroid function tests - hypothyroidism
  • Syphilis and HIV serology
  • Systemic lupus erythematosus serology
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22
Q

What could indicate a CSF leak through the nose?

A
  • high concs. of asialotransferrin (B-transferrin)
    • this protein is gound in v. low concs of this is plasma, nasal secretions and tears
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23
Q

What are the AEIOU TIPS of altered consciousness

A
  • A – alcohols – ethanol, ethylene glycol etc
  • E – epilepsy, electrolyte disorders, hepatic encephalopathy
  • I – insulin (hypoglycaemia), inborn errors of metabolism
  • O – opiates, overdose, oxygen (hypoxia)
  • U – uraemia
  • T – trauma (head injury), temperature (hyperthermia), toxins, tumour (brain tumour)
  • I – infections – sepsis, meningitis, encephalitis
  • P – poisoning, psychogenic
  • S – space-occupying lesions, stroke, seizure, shock
24
Q

What is Neurone Specific Enolase?

A
  • NSE is a glycolytic enzyme released following neuronal cell death
    • this positively correlates with the extent of hypoxic brain injury
    • should be <16ug/L
  • serial measurements 24h apart after a brain injury can indicate the prognosis of the patient
25
Q

Explain how Ionic (osmotic) factor can cause cerebral oedema

A
  • when the solute conc. in the brain exceeds that of the plasma osmotic gradient leads to accumulation of water into the brain –> cerebral oedema and an impaired consciousness
    • the blood-brain barrier remains intact so this pressure is maintained
26
Q

What are some causes of Ionic (osmotic) factors that lead to cerebral oedema?

A
  • Rapid reduction of plasma glucose in treatment od diabetic ketoacidosis or hyperosmolar hyperglycaemia with insulin
  • Hyponatraemia associated causes
    • Excessive IV administration of hypotonic fluids
    • Excessive water intake due to excess ADH secretion
      • syndrome of inappropriate ADH secretion
      • Ectopic ADH secretion- small cell lung carcinoma
      • MDMA (ecstasy)
27
Q

What is Encephalitis and what are it’s clinical symptoms

A
  • Inflammatory conditions of the brain parenchyma
  • altered consciousness persisting longer than 24h,
    • lethargy, irritability, change in personality/ behaviour
  • Fever,
  • Seizures or focal neurological findings attributable to the brain parenchyma
  • Lumbar puncture CSF > 5 WBC x106/L
  • EEG findings suggestive of encephalitis
  • Neuroimaging suggestive of encephalitis
28
Q

Give some causes of Encephalitis

A

Infection:

  • Viral - PCR
    • Person-to-person eg herpes simplex, measles, mumps etc
    • Animal eg ticks (tick-borne encephalitis), dog (rabies)
  • Other pathogens – eg toxoplasma, amoebae

Auto-immune:

  • Post-infectious - acute disseminated encephalomyelitis (ADEM)
  • Tumour-associated - Hu, Yo, Ri, Ma, Amphiphysin, CRMP5/CV2, Tr
  • LGI1 (leucine-rich glioma inactivated 1) or CASPR2 (contactin-associated protein 2) causing ‘limbic encephalitis’.
  • N-methyl-D-aspartate (NMDA) receptor causing NMDAR antibody encephalitis
  • Other - sarcoidosis
29
Q

Give examples of other antibody tests used in neurological diagnosis

A
  • Glutamic acid decarboxylase (GAD) (anti GAD) IgG – Stiff Person Syndrome
  • Voltage-gated Ca2+ channel (anti-VGCC) IgG – (Lambert Eaton) Cerebellar Ataxia
  • Ganglioside GM1 (anti-GM1) IgG and IgM (combined); Ganglioside GQ1b (anti-GQ1b) IgG and IgM – peripheral neuropathy, Miller Fisher and Guillain Barre
  • Myelin associated glycoprotein (MAG) (anti-MAG) IgM – peripheral neuropathy
  • Serum α3 ganglionic receptor – autonomic neuropathy
  • CSF Orexin levels – narcolepsy with cataplexy
  • Aquaporin-4 antibodies (NMO antibodies); Myelin oligodendrocyte glycoprotein (MOG) antibodies – neuromyelitis optica, transverse myelitis
30
Q

Give an example of neuropathological deposition disorders

A
  • Amyloid deposits in the brain in Alzheimer’s disease
  • Alpha-synuclein in clumps inside neurons in Parkinson’s disease – Lewy bodies
  • Iron deposits - neurodegenerative and pituitary – haemochromatosis with raised serum ferritin
  • Copper - neurodegenerative and pituitary – Wilson’s disease – low serum caeruloplasmin
  • Calcium - familial brain calcification
31
Q

Give examples of inborn errors of metabolism affecting the eye

A
  • Cornea clouding – eg Hurler mucopolysaccharide disease, GM1 gangliosidosis
  • Lens cataract – eg galactosaemia, galactokinase deficiency
  • Lens subluxation – eg Marfan’s syndrome, homocystinuria
  • Retina – eg retinitis pigmentosa in Refsum disease, pantothenate kinase 2 deficiency, GM1 gangliosidosis
  • Optic nerve – eg Canavan leukodystrophy
  • Eye muscles – eg progressive external ophthalmoplegia - mitochondrial disorder
32
Q

What approaches can be taken to treat Inborn Errors of Metabolism (IEMs)

A
  • Limiting intake of precursor
  • Supplying missing product
  • Supplying co-factors
  • Reducing accumulated product
  • Blocking pathway above toxic product
  • Enzyme replacement
  • Organ transplantation
  • Chaperone molecules
  • Insertion of genetic material – nuclear and mitochondrial
33
Q

Give an example(s) of an Anxiolytic

A
  • Diazepam
34
Q

Give an example of an Antipsychotic drug(s)

A
  • Chlorpromazine
  • Haloperidol
  • Risperidone
  • Clozapine
35
Q

Drugs used for Mania and Bipolar disorder

A
  • Lithium
36
Q

Give an example of Antidepressant(s)

A
  • Amitriptyline
  • Fluoxetine
37
Q

Give an example of Analgesics

A
  • Paracetamol
  • Ibuprofen
  • Codeine phosphate
  • Morphine
38
Q

Give examples of Antiepileptic drugs

A
  • Carbamazepine
  • Sodium valproate
  • Phenobarbitone
  • Phenytoin
39
Q

Drugs used in Parkinosonianism

A
  • Ropinirole
  • Levodopa
  • Selegiline
  • Entacapone
40
Q

Drugs for Dementia

A
  • Donepezil
41
Q

Give an example(s) of Anaesthetics

A
  • Lidocaine
  • Propofol
42
Q

What drug acts as an is an opioid antagonist?

A

Naloxone

43
Q

Give an example of a neuromuscular blocking drug

A
  • Suxamethonium
44
Q

Give an overview of the action of Phenytoin

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
45
Q

What is Plasma PTH?

A

Parathyroid hormone ( PTH ), also called parathormone or parathyrin, is a hormone secreted by the parathyroid glands that is important in bone remodelling, which is an ongoing process in which bone tissue is alternately resorbed and rebuilt over time. PTH is secreted in response to low blood serum calcium (Ca 2+) levels

46
Q

Side effects of Phenytoin

A
  • activates enzymes that inactivate Vit D leading to decreased calcium absorption
  • promotes PTH secretion to enhance calcium release from bone
47
Q

What is Risperidone and its side effects?

A
  • It is a dopamine receptor blocker used to treat schizophrenia
  • causes hyperprolactinaemia
    • prolactin secretin cells in the anterior pituitary are under inhibitory secretion control by dopamine
    • if DA receptors are blocked prolactin-secreting cells are no longer under inhibition –> increase in serum prolactin (prolactin measured before starting antipsychotics)
48
Q

What are the consequences of hyperprolactinaemia?

A
  • Oligospermia: deficiency of sperm cells in the semen
  • Galactorrhoea: Spontaneous flow of milk from the breast unassociated with breastfeeding or childbirth
  • Oligorrhoea: infrequent menstrual periods regularly going for than 35 days without menstruating
49
Q

What drugs cause Hyperprolactinaemia?

A
  • Antipsychotics
  • Antidepressants
  • Antihypertensive dyrgs
  • Anticonvulsants
  • Prokinetic agents
  • Others: estrogens, anaesthetics, cimetidine…
50
Q

Explain the use and side effects of Lithium

A
  • Lithium is taken by mouth, absorbed in the small bowel and excreted in the urine.
    • small therapeutic window 0.4 – 1.0 mmol/L
  • Toxicity:
    • Acute: vomiting and diarrhoea, dizziness
    • Chronic: coarse tremor, hyperreflexia, nystagmus, ataxia, altered mental state
  • Hypothyroidism: reduces iodine uptake and thyroxine release
  • Increased sensitivity to ADH –> polyuria and risk of hyponatremia
  • causes increased parathyroid secretion –> tendency to hypercalcaemia
  • some evidence of impaired renal function
51
Q

How is Lithium therapy monitored?

A
  • Measurement of serum lithium concentrations – usually every 3 months until steady state
  • Renal function – U&E
  • Thyroid function
  • Serum calcium
52
Q

What are some causes of drug-induced hyponatraemia?

A
  • Increased ADH
    • Antidepressants (TCA, SSRI, MAO); antipsychotic (phenothiazines, butyrophenones e.g. haloperidol); antiepileptics (carbamazepine, oxcarbazepine, valproate); opiates
  • Potentiation of ADH
    • Antiepileptics (carbamazepine, lamotrigine)
  • Reset osmostat
    • Antidepressants (venlafaxine); antieplipetics (carbamazepine)
53
Q

gonadtrophin part of the cell groups that release the mammalian sex hormones

Give an overview of drug-induced hypogonadism

A
  • Opiate induced hypogonadism: affects males and females
    • Stimulation of opioid receptors in the hypothalamus leading to reduced gonadotrophin secretion
    • Prescribed and recreational e.g. heroin
  • Hyperprolactinaemia, see drugs above.
  • Antiepileptics increase SHBG (reduce free androgens) and also suppress HPA axis, again causing hypogonadism in men and women.
54
Q

Explain Pseudocholinesterase deficiency (suxamethonium apnoea)

A
  • Suxamethonium mimics the action of acetylcholine in depolarisation at the neuromuscular junction but is hydrolysed much more slowly giving it a prolonged effect - used as a muscle relaxant for intubation during surgery
  • decreased concs. of pseudocholinesterase will lead to prolonged effect of this drug
    • hence when pseudocholinesterase is deficient the patient will take a while to breathe and move on their own after surgery
  • Also increased sensitivity to other drugs
    • procaine (local anaesthetic)
    • some pesticides
55
Q

How can pseudocholinesterase deficiency be identified?

A
  • taking serum samples,
  • Inhibitor studies are used to determine the phenotype as this indicates the extent of the risk of apnoea
  • autosomal recessive BSCHE gene (butylrylcholinesterase)
  • more common in Persian Jews and Alaska Natives
  • screen relative and occupation role in pesticide workers

202: Theme 1 (14 decks)

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