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CSF NORMAL Bacterial Viral Pretreated Other eg

Cryptococcal TB
WCC 5WBC/ mm3 >1000 cells/mm3 < 500 cells/mm3 Mixed PMN & TB Lymphs
1-3 PMN/mm3 Usually > 500 (encephalitis = same) Lymphs Crypto: ?Lymphs
5RBC/ mm3 Occasionally > 10,000 Rarely > 1000 Absolute counts Eosinophils: TB,
zero eosinophil/mm3 >50% Lymphs in: 100% Lymphocytes unaffected Mycoplasma pneumonia,
parasites, rickettsia, fungi
May see basophils 10% of bacterial < 48 Hrs may have + lymphoma, leukaemia,
Neonate 20WBC/ mm3 25% of bacterial significant No. PMN SAH, obstructive
Falsely low if analysed when WCC<1000 (espec enterovirus) hydrocephalus
>60min post collection NB 3% WCC<100
GLUCOSE 60% of serum level < 40-50% serum Slight or normal or normal
Hyperglycaemia: May be normal
closer to 40% < 30% in
PROTEIN 15-45mg/dL High (>150mg/dL) Normal (<150mg/dL) or normal High
Neonate 20-170mg/dL >220mg/dL = <1%
chance viral
GRAM negative 70-80% Sensitive -ve to 20-50% sens. India Ink detects
STAIN Varies with stage of G+ve may appear 30% of Cryptococcal
disease, No. of as G-ve AFB stain 80% sens
organisms present Stain varies with (if >10ml fluid!!)
damaged cells
Culture -ve +ve -ve -ve in 30% -ve
Lactate <35mg/dL >35mg/dL normal
RBC <2
Blood Meningococcus Meningococcus
Cultures 50% sens 5% sens
Completely normal LP seen in 2-3% of confirmed (culture +ve) meningitis
Note: Predominant cell types give rough guide only as to aetiology. Definitive test = culture
Note: PMN = PolyMorphoNuclear Lymphocytes = GRANULOCYTES = Neutrophils, Basophils, Eosiniphils

Trivia: 50% of Pneumococcal meningitis have pneumonia on CxR (as do 20% of Meningococcus, < 10% of HiB)
Cells: If WCC = 500-1000 can be either bacterial or viral
Turbidity caused by WCC > 200 cells/mm3
CSF WCC: NOT elevated by seizures (blood WCC can be)
Bloody Tap: subtract 1 WBC for every 700 (Rosen) to 1000 (Dunn) RBC

CSF Protein:
Traumatic tap? Subtract 1mg/dL for each 1000 RBC to get accurate level.
Elevated in: Meningitis, encephalitis, SAH, CNS vasculitis, syphilis, neoplasm, demyeliniation
Markedly elevated (>1000mg/dL) in relatively well patient = suggests fungal infection
Stay elevated for weeks/months post infection not useful as marker of recovery

CSF Glucose
Low in: bacterial, TB, fungal ( 1.0 mmol/L strongly predictive of bacterial infection)
Also: Malignancy, SAH, CNS Sarcoid, Viral infection (Mumps, eneterovirus, HSV, LCM lymphocytic choriomeningitis)
Higher in ventricles than lumbar CSF
Hyperglycaemia: Takes 4hrs for IV glucose to equilibrate with CSF (ie after treatment for hypoglycaemia) so need to wait to compare CSF to
serum glucose in this setting (earlier comparison will give falsely low CSF level compared to serum)

Raised in bacterial infection rarely adds extra information to other parameters

Opening pressure: Normal 5-20cm H2O (in lateral recumbent position)

Increased in: Sitting position, bacterial, TB, fungal meningitis, various non-infective conditions, obese, tense, marked muscle contraction

Ag Tests: Electrophoresis, latex/coagglutinaition. Latex most rapid & most commonly available
Useful if pretreated with ABx. Increased sensitivity if performed on CSF, urine & blood simultaneously
Sensitivity: Neisseria (50-90%), Strep (50-100%) Haemophilus (80%). NOTE: MANY FALSE NEGATIVES
Cryptococcal Ag: 90% sens/spec
Syphilis: VDRL

PCR: Highly sensitive & specific for: HSV, Enterovirus, TB, Cryptococcus
Reserve for high risk patients/clinical suspicion of atypical organism
Bacterial: higher sensitivity than Ag tests, nearly 100% specific

Meningococcus Chemoprophylaxis:
For contacts who may be SOURCE
Note: Carriage is an immunising process in most people (systemic Ab response)
Also for close contacts

If traumatic tap & CSF protein > 150mg/dL likely that enough RBC introduced to cause Xanthochromia
If CSF protein < 150mg/dL & Xanthochromia present likely due to SAH
NB: High CSF protein (> 150mg/dL) on its own may cause Xantho
as can Systemic hyperbilirubinaemia (bilirubin > 10-15mg/dL)

Need at lest 10-15ml of fluid
Tuberculin Skin Testing

What is it?

The Mantoux tuberculin skin test (TST) is the standard method of determining whether a person is infected with Mycobacterium tuberculosis.
Reliable administration and reading of the TST requires standardization of procedures, training, supervision, and practice.

How is the TST Administered?

The TST is performed by injecting 0.1 ml of tuberculin purified protein derivative (PPD) into the inner surface of the forearm. The injection
should be made with a tuberculin syringe, with the needle bevel facing upward. The TST is an intradermal injection. When placed correctly, the
injection should produce a pale elevation of the skin (a wheal) 6 to 10 mm in diameter.

How is the TST Read?

The skin test reaction should be read between 48 and 72 hours after administration. A patient who does not return within 72 hours will need to be
rescheduled for another skin test.

The reaction should be measured in millimeters of the induration (palpable, raised, hardened area or swelling). The reader should not measure
erythema (redness). The diameter of the indurated area should be measured across the forearm (perpendicular to the long axis).

How Are TST Reactions Interpreted?

Skin test interpretation depends on two factors:

Measurement in millimeters of the induration

Persons risk of being infected with TB and of progression to disease if infected
Classification of the Tuberculin Skin Test Reaction
An induration of 10 or more
millimeters is considered
positive in

An induration of 5 or more millimeters is -Recent immigrants (< 5 years)

considered positive in from high-prevalence countries

-HIV-infected persons -Injection drug users

-A recent contact of a person with TB disease -Residents and employees of

high-risk congregate settings >An induration of 15 or more millimeters is considered
-Persons with fibrotic changes on chest radiograph positive in any person, including persons with no known risk
consistent with prior TB -Mycobacteriology laboratory factors for TB. However, targeted skin testing programs
personnel should only be conducted among high-risk groups.
-Patients with organ transplants
-Persons with clinical
-Persons who are immunosuppressed for other conditions that place them at
reasons (e.g., taking the equivalent of >15 mg/day high risk
of prednisone for 1 month or longer, taking TNF-
antagonists) -Children < 4 years of age

- Infants, children, and

adolescents exposed to adults
in high-risk categories
What Are False-Positive Reactions?

Some persons may react to the TST even though they are not infected with M. tuberculosis. The causes of these false-positive reactions may
include, but are not limited to, the following:

Infection with nontuberculosis mycobacteria

Previous BCG vaccination
Incorrect method of TST administration
Incorrect interpretation of reaction
Incorrect bottle of antigen used

What Are False-Negative Reactions?

Some persons may not react to the TST even though they are infected with M. tuberculosis. The reasons for these false-negative reactions may
include, but are not limited to, the following:

Cutaneous anergy (anergy is the inability to react to skin tests because of a weakened immune system)
Recent TB infection (within 8-10 weeks of exposure)
Very old TB infection (many years)
Very young age (less than 6 months old)
Recent live-virus vaccination (e.g., measles and smallpox)
Overwhelming TB disease
Some viral illnesses (e.g., measles and chicken pox)
Incorrect method of TST administration
Incorrect interpretation of reaction

Who Can Receive a TST?

Most persons can receive a TST. TST is contraindicated only for persons who have had a severe reaction (e.g., necrosis, blistering, anaphylactic
shock, or ulcerations) to a previous TST. It is not contraindicated for any other persons, including infants, children, pregnant women, persons
who are HIV-infected, or persons who have been vaccinated with BCG.

How Often Can TSTs Be Repeated?

In general, there is no risk associated with repeated tuberculin skin test placements. If a person does not return within 48-72 hours for a
tuberculin skin test reading, a second test can be placed as soon as possible. There is no contraindication to repeating the TST, unless a previous
TST was associated with a severe reaction.

What is a Boosted Reaction?

In some persons who are infected with M. tuberculosis, the ability to react to tuberculin may wane over time. When given a TST years after
infection, these persons may have a false-negative reaction. However, the TST may stimulate the immune system, causing a positive, or boosted
reaction to subsequent tests. Giving a second TST after an initial negative TST reaction is called two-step testing.

Why is Two-Step Testing Conducted?

Two-step testing is useful for the initial skin testing of adults who are going to be retested periodically, such as health care workers or nursing
home residents. This two-step approach can reduce the likelihood that a boosted reaction to a subsequent TST will be misinterpreted as a recent

Can TSTs Be Given To Persons Receiving Vaccinations?

Vaccination with live viruses may interfere with TST reactions. For persons scheduled to receive a TST, testing should be done as follows:

Either on the same day as vaccination with live-virus vaccine or 4-6 weeks after the administration of the live-virus vaccine
At least one month after smallpox vaccination
2. INTRODUCTION In the normal pleural space, there is a steady state in which there is a roughly equal rate of the formation (entry) and
absorption (exit) of liquid (figure 1). (See "Mechanisms of pleural liquid turnover in the normal state".) This balance must be disturbed in order
to produce a pleural effusion. Thus, there must be an increase in entry rate and/or a reduction in exit rate. It is likely that both mechanisms
contribute to effusion formation for the following reasons:

An isolated increase in entry rate, unless massive, is unlikely to cause a large effusion because the absorbing pleural lymphatics have a
large reserve capacity to deal with excess pleural liquid. If, for example, an artificial hydrothorax is instilled into the pleural space of an
awake sheep, the exit rate can increase to 0.28 mL/kg per h, which is 28 times the baseline rate [1].
An isolated decrease in exit rate is also unlikely to cause a large effusion because the normal entry rate is low. Even if the exit of liquid
ceased entirely, accumulation of liquid would take many days to become evident. As an example, the normal entry rate of 0.01 mL/kg per
h is equivalent to a total of 14.4 mL/day in a 60 kg woman; at this rate, it would take 34 days for 500 mL to accumulate in the pleural
space if there were no exit. Of note, the effusion would presumably be a transudate, since the normal entering liquid is low in protein.

INCREASED FLUID ENTRY Excess liquid filters out of microvessels based on a balance of hydrostatic and osmotic forces across a
semipermeable membrane [2,3]. These forces are well described in the Starling equation, in which the hydrostatic forces that filter water out of
the vessel are balanced by osmotic forces that reabsorb water back into the vessel [4,5].

Flow = k x [(Pmv - Ppmv) - s (mv - pmv)]

In this equation, k is liquid conductance of the microvascular barrier, Pmv and Ppmv represent hydrostatic pressure in the microvascular and
perimicrovascular compartments, s is the reflection coefficient for total protein and ranges from 0 (completely permeable) to 1 (completely
impermeable), and mv and pmv represent protein osmotic pressure in microvascular and perimicrovascular liquids, respectively. In normal
microvessels, there is ongoing filtration of a small amount of low protein liquid. The flow can increase with changes in various parameters of the
Starling equation.

Increase in permeability An increase in flow can be due to increases in either liquid conductance (an increase in k) or protein permeability (a
decrease in reflection coefficient). If the endothelial barrier becomes more permeable to liquid and protein, for example, there will be an increase
in flow of a higher protein liquid. Because absorption does not alter the protein concentration of pleural liquid, pleural liquid with a high protein
concentration indicates its origin from a circulation across an area of increased permeability. (See "Mechanisms of pleural liquid turnover in the
normal state", section on 'Evidence for bulk flow'.)

Increase in microvascular pressure An elevation in microvascular pressure (Pmv) is usually induced by an elevation in venous outflow
pressure. Increases in arterial pressure are less likely to be transmitted to the microvessels because of the high precapillary resistance and
autoregulation of arteriolar tone.

Elevations in either systemic venous pressure (affecting the parietal pleura) or pulmonary venous pressure (affecting the visceral pleura) can lead
to an increase in pleural liquid formation and the development of a pleural effusion. Vascular permeability is unchanged in this setting; as a
result, the increased flow is associated with a greater sieving of proteins, leading to a filtrate with a lower protein concentration than normal
(with a pleural liquid-to-plasma protein ratio of less than 0.15).

Of course, most effusions formed due to increased microvascular pressures, ie, transudative effusions, have a pleural liquid-to-plasma protein
ratio much higher than this, between 0.4 and 0.5. This fact demonstrates that most liquid must arise from a source other than the systemic
circulation of the pleural membranes. The likely source is the large non-systemic circulation adjacent to the pleural space, namely the pulmonary
circulation of the nearby lung. In the normal state, lung interstitial liquid, eg, lymph, filtered from the low pressure pulmonary circulation has a
protein concentration ratio (lung to plasma protein concentration ratio) of 0.7, but with increased flow due to increased pulmonary microvascular
pressures, this ratio falls to 0.4-0.5 [6]. This lung interstitial edema liquid then is the likely source of the majority of the hydrostatic pleural
effusion [7].

How does the lung liquid reach the pleural space? When the rate of filtrate formation exceeds the absorptive capacity of the lung lymphatics, the
filtrate accumulates in the peribronchovascular spaces ("cuffs") [8]. Once in these interstitial spaces, the liquid is not accessible to lung
lymphatics [9]. Thus, although the lymphatics are undeniably important in removing liquid as it is filtered from the pulmonary circulation, they
cannot account for the clearance of already established edema from the lung [10]. This interstitial edema probably leaves the lung by flowing
down pressure gradients along the interstitial spaces (interlobular septae, peribronchovascular bundles and visceral pleura) of the lung toward
either the mediastinum or the pleural space. The entry of large amounts of lung interstitial liquid into the pleural space will elevate the overall
protein concentration of the pleural liquid, giving a ratio of 0.40-0.50, the expected range for a transudative effusion [10].
Decrease in pleural pressure A decrease in pleural pressure, as seen with significant atelectasis, may alter the balance of forces described in
the Starling equation by reducing the pressures surrounding the nearby microvessels. This decrease in perimicrovascular pressures (Ppmv) can
enhance filtration across the microvascular barrier of a low protein liquid (with a pleural liquid-to-plasma protein ratio of less than 0.15).

Decrease in plasma osmotic pressure Hypoproteinemia (due to hypoalbuminemia) will decrease the plasma oncotic pressure (mv), thereby
increasing the forces favoring filtration until the balance is restored. By itself, hypoproteinemia can probably induce small effusions with a low
protein concentration. In addition, hypoproteinemia can lower the threshold for effusion formation when other Starling forces are changed. In a
study of hospitalized patients with AIDS, for example, hypoproteinemia alone was the apparent cause of 19 percent of all pleural effusions [11].
Together with other factors, a lower plasma protein concentration may have contributed to effusion formation in many more patients, because, in
general, all patients with effusions had a lower plasma albumin concentration than those without effusion (2.5 versus 3.4 g/dL [25 versus 34

DECREASED FLUID EXIT A decrease in exit rate reflects a reduction in lymphatic function. Because lymphatic function is poorly
understood, much of this discussion is speculative. Unlike blood vessels, lymphatic vessels have one-way valves and propel lymph using both
their own rhythmic contractions and the respiratory motions of the chest wall. In addition, flow is affected by lymphatic patency, availability of
liquid, and the pressures influencing filling (pleural pressure) and emptying (systemic venous pressure) of lymphatics [12,13].

Intrinsic factors A number of factors can interfere with or inhibit the ability of lymphatics to contract, including:

Cytokines and products of inflammation (eg, endotoxins)

Endocrine abnormalities (eg, hypothyroidism)
Injury due to radiation or drugs (eg, chemotherapeutic agents)
Infiltration of lymphatics by cancer
Anatomic abnormalities (eg, yellow nail syndrome)

Extrinsic factors Multiple extrinsic factors can inhibit lymphatic function although the lymphatics themselves are normal. These include:

Limitation of respiratory motion (eg, diaphragm paralysis, lung collapse, pneumothorax)

Extrinsic compression of lymphatics (eg, pleural fibrosis, pleural granulomas)
Blockage of lymphatic stomata (eg, fibrin deposition on pleural surface, pleural malignancy)
Decreased intrapleural pressure (eg, trapped lung caused by a fibrous rind on the visceral pleura)
Increased systemic venous pressure - Acutely, increases in venous pressure may decrease lymphatic flow because of the higher
downstream pressures; chronically, the lymphatics may be able to adapt.
Decreased liquid availability - After pneumothorax, for example, liquid will be in contact with fewer lymphatic stomata and may
accumulate in the pleural space.