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Chemistry year 2 > Lecture 5 > Flashcards

Lecture 5 Flashcards

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1
Q

What is CSF

A

clear and colorless
surrounds the brain
formed by ependymal cells

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2
Q

how is csf produced

A

chroid plexus
ultrafiltrate of plasma

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3
Q

clinical importance of csf

A

changes are systemic changes with a lag compared to serum - especially for glucose and serum

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4
Q

What are the three layers of the meninges

A

Dura Mater: outermost and closest to the skull.

Arachnoid: middle layer with spider web-like appearance.

Pia Mater: delicate inner layer attached to the CNS.

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5
Q

functions of csf

A

support - acts as cushion , absorbs shock

Excretion - removes waste

environment - maintains control environment

transport- nutrients and hormones

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6
Q

what is the BBB

A

-physiological barrier separating the ECF and CNS parenchyma

has selective permeability with some needing active transport - glucose
-factors like molecular weight, protein binding and lipid solubility affect how things cross

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7
Q

what can affect BBB permeability

A

inflammation
neovascularity
toxins
developmental stages

changes are important for diagnosing CNS diseases

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8
Q

why would you need to look at the csf

A

Trauma: Intracranial bleeding, subarachnoid hemorrhage.

Infectious Diseases: Meningitis (bacterial, viral, fungal), encephalitis, AIDS, Lyme disease.

Inflammatory Diseases: Multiple sclerosis.

Malignancy: Tumors, metastatic cancer.

Hydrocephalus: Obstructed CSF leading to increased brain pressure

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9
Q

What tubes are used for csf

A

-collected via lumbar puncture between c3 and c4

3 tubes collected for different tests
1- chem glu pt
2-micro - c&s
3- hem - cell count

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10
Q

What do you look for in a macroscopic examination of CSF

A

Color
normal - colorless
Xanthochromia - yellow =old blood breakdown
Red- blood present - traumatic tap

Transparency
cloudy- cells, bacteria high protein

Clots- poor puncture

Pellicle- TB meningitis

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11
Q

What do you look for in a microscopic examination

A

micro - gram for bacterial, viral or TB

Hem for cell count, diff staining (wright stain for cancer)

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12
Q

Biochemical testing of CSF - glucose

A

routine biochem test - glu and tp

plasma glucose take 2 hours to be reflected in csf

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13
Q

Glucose is decreased in

A

Bacterial meningitis - bacterial eat the glucose

Fungal and TB meningitis

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14
Q

glucose normal or slightly decreased in

A

Viral meningitis, MS and subarachnoid hemorrhage

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15
Q

Glucose is measured by

A

glucose oxidase method- glucose in csf reacts with O2 and H2O-= gluconic acid and h2o2 which react with chromogen = glucose concentration

Hexokinase - phosphorylation of glucose to g6p by hexokinase and G6P is oxidized by NAD to NADH increase in ABs at 340 proportional to concentration

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16
Q

Sources of Error in measurement methods

A

Glucose Oxidase- affected by reducing substances like ascorbic acid, bilirubin, glutathione, uric acid, and hemoglobin, can
lead to falsely low glucose readings

Hexokinase method- not affected much by reducing substances but hexoses like fructose and gross hemolysis can impact

Blood contamination - blood in CSF falsely increases glucose as there is a higher glucose presence in blood

Delayed Analysis- glycolysis in csf sample can decrease glucose if there is delay in processing

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17
Q

why is protein measurement in csf important

A

indicated neurological disease
-in healthy people protein cant get into csf due to BBB
-normal RI can vary due to method and instrument used.

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18
Q

When will you see increase protein in csf

A

Bacterial, Fungal, and TB Meningitis: Marked elevation due to the increased
permeability of the BBB.

Viral Meningitis: Moderate elevation.

Multiple Sclerosis: Mild to moderate elevation

Subarachnoid Hemorrhage: due to the presence of blood in CSF.

Tumors, Abscesses, and CNS Degenerative Diseases: due to increased production or decreased
clearance of proteins.

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19
Q

when would you see Decreased Protein Levels

A

CSF Leak or Hyperthyroidism (increase production leading to dilution)

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20
Q

Measurement Methods for TP in CSF

A

Turbidimetric method: proteins in CSF cause turbidity and when mixed with acids like trichloroacetic acid the degree of turbidity is measure photometrically

Dye binding methods: prot bind to coomassie brilliant blue or Ponceau S = color change measured spectrophotometrically

Electrophoresis
-proteins separated based on size and charge which helps with MS diagnosis (olig)

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21
Q

Sources of Error when measuring TP

A

Contamination - blood contamination falsely increases

method errors - different methods diff answers makes sure everything is consistent

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22
Q

significance of decreased CL in CSF

A

Tuberculous Meningitis: A marked reduction in CSF chloride can be seen, - diagnostic marker.

Bacterial Meningitis: Mild to moderate decrease.

Cerebral Edema or Brain Tumor: due to
altered electrolyte transport across the blood-brain barrier.

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23
Q

Increased CSF Chloride:

A

Dehydration or Hyperchloremic Acidosis: Elevated chloride levels can be
observed.

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24
Q

Measurement Methods: of csf CL

A

Ion-Selective Electrodes (ISE):

o Chloride levels are most accurately measured using ion-selective electrodes,

rapid and precise readings.

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25
Q

Sources of Error in CL measurement

A

Contamination: contamination with plasma or other fluids can alter chloride
levels.

Sample Handling: Delays or improper storage can lead to changes in electrolyte
concentrations, affecting the accuracy of the results.

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26
Q

CSF Immunoglobulin

A

IgG
-diagnosis of inflammatory
and autoimmune diseases of the central nervous system

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27
Q

Oligoclonal Bands (OCBs):

A

bands of immunoglobulins detected in the CSF but not in
the serum, indicative of intrathecal antibody production.

28
Q

Clinical Significance:
of OLIG

A

Multiple Sclerosis (MS): The presence of OCBs is a hallmark of MS, found in
approximately 90% of patients. diagnostic criteria for MS.

Other Inflammatory CNS Conditions: OCBs can also be present in conditions like
neurosyphilis, chronic CNS infections, and autoimmune encephalitis.

29
Q

Measurement Methods: of OLIG

A

Isoelectric Focusing (IEF) with Immunoblotting:

The gold standard for detecting OCBs where you separate proteins by their
isoelectric point and identifyimmunoglobulines with specific antibodies.

30
Q

Sources of Error for OLIG

A

Blood Contamination: The presence of plasma proteins can complicate the
interpretation of OCBs.

Cross-Contamination: handle carefully to avoid cross-contamination
between patient samples, which could lead to false-positive results.

31
Q

CSF Cytology and Flow Cytometry what does it do

A

examination of cells in the CSF

32
Q

Normal Findings: in cytology

A

Lymphocytes and Monocytes: In a healthy individual, CSF predominantly contains small
numbers of lymphocytes and monocytes.

33
Q

Clinical Significance: of looking at cells
Malignant Cells:

A

in CNS Tumors: finding malignant cells for primary brain tumors or metastasis to the CNS

Leukemia and Lymphoma: detected in the CSF in
patients with hematological malignancies

34
Q

Clinical Significance: of looking at cells

Infectious Agents:

A

Fungal Infections: Fungal elements like Cryptococcus can be identified.

Bacterial Infections: Gram-negative bacteria or acid-fast bacilli in cases of
tuberculosis can be detected.

35
Q

how is Flow Cytometry used for CSF testing

A

immunophenotyping
cells, looking at cell populations, useful in leukemia and lymphoma.

36
Q

Sources of Error: in flow cytometery

A

Sample Handling: processing delays lead to cell lysis, resulting in poor-quality samples for cytological examination.

Contamination: Care must be taken to avoid contamination with external cells or
pathogens.

37
Q

Subarachnoid Hemorrhage (SAH):

what will you see in CSF

A

Xanthochromia: yellow CSF due to the breakdown of hemoglobin to bilirubin is a key feature of SAH. detected spectrophotometrically.

Elevated Protein: Due to the presence of blood, protein levels are elevated.

38
Q

Multiple Sclerosis (MS):

what will you see in CSF

A

Oligoclonal Bands (OCBs): , the presence of OCBs in the CSF but not
in the serum is indicative of MS.

Increased IgG Index: The IgG index is calculated to assess intrathecal IgG synthesis, which is elevated in MS.

39
Q

Bacterial Meningitis

what will you see in CSF:

A

Elevated CSF protein, decreased glucose, increased WBC count mostly neutrophils.

Gram stain and culture are used for pathogen ID.

40
Q

Viral Meningitis
what will you see in CSF:

A

Normal or slightly elevated protein, normal glucose, and increased WBC count
with a lymphocytic predominance.

PCR is used for viral pathogen detection.

41
Q

Guillain-Barré Syndrome (GBS):

what will you see in CSF:

A

Albuminocytologic Dissociation: Elevated CSF protein with a normal cell count is
characteristic of GBS.

  • Electrophysiological Studies: Complementary to CSF analysis, these studies help
    confirm the diagnosis
42
Q

What is CSF Protein Electrophoresis used for

A

to identify specific protein patterns in the CSF, aiding
in the diagnosis of various neurological conditions

43
Q

Normal Protein Patterns: in CSF protein electrophoresis

A

Albumin: The most prominent protein in the CSF

  • Prealbumin, Transferrin, and Transthyretin: present in smaller quantities.
44
Q

Clinical Significance:
* Oligoclonal Bands (OCBs)
in CSF protein electrophoresis

A

presence can indicate
multiple sclerosis and other inflammatory CNS diseases.

45
Q

Clinical Significance:
Increased Alpha-2 Globulin:

in CSF protein electrophoresis

A

Acute Phase Response:

An increase in alpha-2 globulin indicates acute phase response in CNS infections or inflammation.

46
Q

Clinical Significance:
Monoclonal Bands:
in CSF protein electrophoresis

A

CNS Lymphoma or Paraproteinemia: presence of monoclonal
immunoglobulin bands suggest CNS lymphoma or systemic
paraproteinemia with CNS involvement.

47
Q

Interpretation of Abnormal Patterns
in CSF protein electrophoresis

A

Albuminocytologic Dissociation:

o Seen in Guillain-Barré Syndrome (GBS), marked increase in
CSF protein without a corresponding increase in cell count.

Beta-2 Transferrin:

o Specific for CSF, used to confirm the presence of CSF in nasal or ear
discharge, in cases of suspected CSF leak.

48
Q

Sources of Error
in CSF protein electrophoresis

A

Sample Contamination: Contamination with blood or plasma can introduces extraneous
proteins, complicating the interpretation of results.

  • Degradation of Proteins: Improper storage or delays in analysis can lead to protein degradation, affecting the accuracy of electrophoresis.
49
Q

CSF lactate

A

critical marker used to distinguish between different types of meningitis and other conditions affecting the central nervous system.

50
Q

Clinical Significance:
* Elevated Lactate Levels:

A

Bacterial Meningitis: Significantly elevated lactate levels (>3.5 mmol/L) are often
indicative of bacterial infection.

o Fungal and Tuberculous Meningitis: moderate

o Hypoxia and Ischemic Conditions: due to anaerobic metabolism
under conditions of reduced oxygen supply.

51
Q

Normal Lactate Levels: mean

A

helps with differential diagnosis.

52
Q

Sources of Error while measuring lactate

A

Delay in Analysis: Lactate levels can increase if the CSF sample is not analyzed promptly
due to ongoing glycolysis by cells in the fluid.

  • Blood Contamination: Can falsely elevate lactate levels if the sample is contaminated
    with blood.
53
Q

CSF Cell Count and Differential needed to

A

diagnosing infections,
hemorrhages, and inflammatory conditions affecting the CNS.

there are no RBCs in a persons csf

54
Q

Clinical Significance:
* Elevated WBC Count (Pleocytosis):

in cell count

A

Bacterial Meningitis: Marked increase, mostly neutrophils.

o Viral Meningitis: Increase with lymphocytes

o Fungal and TB Meningitis: Lymphocytes
.
o Subarachnoid Hemorrhage and CNS Malignancies: increase in both WBCs and RBCs.

55
Q

Measurement Methods of cell count

A

manual under a microscope

automated

56
Q

Sources of Error:
in cell count

A

Traumatic Tap: Can introduce blood into the CSF sample,

  • Sample Handling: Delays lead to cell lysis, which may affecting count accuracy
57
Q

increase of Myelin Basic Protein (MBP): means

A

demyelinating diseases such as MS

58
Q

Lactate Dehydrogenase (LDH):
o Increased LDH

A

indicate cell damage or breakdown, seen in bacterial meningitis, CNS tumors, and
subarachnoid hemorrhage. distinguished between viral and bacteria (higher)
-can increase after traumatic brain injury reflecting extent of damage

ISOENZYMES can pinpoint source if from brain or systemic circulation

59
Q

: Increased CK-BB Isoform

A

Specific for the brain, elevated
indicate CNS injury or infarction

can increase after traumatic brain injury reflecting extent of damage

60
Q

Neurotransmitters:
* Serotonin (5-HT):

A

decreased
depression, anxiety disorders, and other
psychiatric conditions

61
Q

Neurotransmitters: Dopamine:
o Decreased Levels:

A

Parkinson’s disease and other movement disorders

62
Q

Glutamate:
o Increased Levels

A

h excitotoxicity in conditions like stroke,
traumatic brain injury, and epilepsy

63
Q

o Beta-Amyloid (Aβ42)
Tau Protein:

A

Beta-Amyloid (Aβ42) Decreased levels indicate Alzheimer’s deposition of amyloid plaques in the brain.

Tau Protein: increased levels markers of neurofibrillary tangles and neuronal injury in Alzheimer’s disease.

ELISA (Enzyme-Linked Immunosorbent Assay):

csf biomarkes

64
Q

o Alpha-Synuclein
o DJ-1 Protein

A

o Alpha-Synuclein-hallmark of Parkinson’s disease can be seen at different levels in CSF

o DJ-1 Protein- biomarker for Parkinson’s disease,
reflecting oxidative stress and neuronal damage.

65
Q

o Neurofilament Light Chain (NFL)

A

axonal damage increased in ALS and motor diseases

Chemistry year 2 (12 decks)

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