Fetal hemoglobin and rh incompatibilityrohini sane
A comprehensive presentation on fetal hemoglobin & Rh incompatibility for undergraduate medical, dental, biotechnology & pharmacology students for self-learning .Presentation has physical & chemical properties of fetal hemoglobin along with its function. Binding affinity for O₂ of HbF and oxygen dissociation curve for HbF elucidated with suitable diagrams. Molecular constitution of Embryonic Hb ( Grover I &Grover II )with electrophoretic patterns are presented here . Importance of Kleihauer staining for detection of fetal cells is described briefly.
Diagrammatic representation of Rh- incompatibility is done for complete understanding of the concept. Signs & symptoms Kernicterus are presented diagrammatically.
Direct and indirect Coomb’s Test for Rh- incompatibility for diagnosis of Erythroblastosis Fetalis is illustrated. Biochemical aspects of Hemolytic Disease of Newborn (HDN) and Physiological /Neonatal Jaundice are presented. Comparison of Causes & biochemical findings for Hemolytic Jaundice along hepatic and obstructive jaundice is done in this presentation.
Molecular mechanism involved in biosynthesis of Hb Bart and Hb H along with their electrophoretic patterns for their detection are illustrated.
Hereditary persistent fetal Hb( HPFH ) & Point mutations causing HPFH are described in lucid manner. Google images are used for intense impact of the subject.
CSF - Cerebrospinal fluid examination - from tapping to pathological diagnosisAshish Jawarkar
This is a series of notes on clinical pathology, useful for undergraduate and postgraduate students, as well as practising pathologists. Prepared from standard text books with data in tabular and easily readable format
This presentation is focused on diagnostic utility of Red blood cell indices which will be very useful for undergraduate and postgraduate of medical field.
Fetal hemoglobin and rh incompatibilityrohini sane
A comprehensive presentation on fetal hemoglobin & Rh incompatibility for undergraduate medical, dental, biotechnology & pharmacology students for self-learning .Presentation has physical & chemical properties of fetal hemoglobin along with its function. Binding affinity for O₂ of HbF and oxygen dissociation curve for HbF elucidated with suitable diagrams. Molecular constitution of Embryonic Hb ( Grover I &Grover II )with electrophoretic patterns are presented here . Importance of Kleihauer staining for detection of fetal cells is described briefly.
Diagrammatic representation of Rh- incompatibility is done for complete understanding of the concept. Signs & symptoms Kernicterus are presented diagrammatically.
Direct and indirect Coomb’s Test for Rh- incompatibility for diagnosis of Erythroblastosis Fetalis is illustrated. Biochemical aspects of Hemolytic Disease of Newborn (HDN) and Physiological /Neonatal Jaundice are presented. Comparison of Causes & biochemical findings for Hemolytic Jaundice along hepatic and obstructive jaundice is done in this presentation.
Molecular mechanism involved in biosynthesis of Hb Bart and Hb H along with their electrophoretic patterns for their detection are illustrated.
Hereditary persistent fetal Hb( HPFH ) & Point mutations causing HPFH are described in lucid manner. Google images are used for intense impact of the subject.
CSF - Cerebrospinal fluid examination - from tapping to pathological diagnosisAshish Jawarkar
This is a series of notes on clinical pathology, useful for undergraduate and postgraduate students, as well as practising pathologists. Prepared from standard text books with data in tabular and easily readable format
This presentation is focused on diagnostic utility of Red blood cell indices which will be very useful for undergraduate and postgraduate of medical field.
I have listed out the LE cells structure and Microscopical examinaton of LE CELLS, Difference between tart cells and le cells, clinical symptoms and diagnostic procedure.
It is fluid which is present
in the pericardial cavity of
heart b/w parietal pericardium n visceral pericardium.
The pericardial cavity is a
potential space lined by
mesothelium of the visceral n parietal pericardium.
I have listed out the LE cells structure and Microscopical examinaton of LE CELLS, Difference between tart cells and le cells, clinical symptoms and diagnostic procedure.
It is fluid which is present
in the pericardial cavity of
heart b/w parietal pericardium n visceral pericardium.
The pericardial cavity is a
potential space lined by
mesothelium of the visceral n parietal pericardium.
CSF:
Derived through ultrafilteration and secretion through choroid plexus, produced at the rate of 500 ml/day.
Provides physical support, collects wastes, circulates nutrients and lubricates the CNS.
Normal CSF volumes:
In Adults: 90 - 150 ml
In Neonates: 10 - 60 ml
Total CSF volume is replaced every 5-7 hours.
COLLECTION
Lumbar puncture, Cisternal puncture, Lateral cervical puncture, Shunts and cannulas
Opening pressure – 90-180 mm H2O
Approximately 15-20 cc fluid collected
LAB
REQUIRED
Opening CSF pressure
Total cell count
Differential cell count
Glucose
Total protein
OPTIONAL
Cultures, Gram stain, AFB, Fungal and bacterial
antigens, Enzymes, PCR, Cytology, Electrophoresis,
VDRL, D-Dimers
Parkinson's disease is a brain disorder that progressively affects a person’s ability to control body movements, caused by a disorder of certain nerve cells in a part of the brain that produces dopamine, a chemical messenger the brain uses to help direct and control body movement.
Early diagnosis of Parkinson's disease gives you the best chance of a longer, healthier life. This presentation covers the information about biomarkers for Parkinson Diseases which include biological, physiological and imagine candidate / novel biomarkers.
csf is the fluid which is present around the brain and spinal card as a shock absorber, provide nutrition and keep them wet. CSF analysis is an important tool in the diagnosis of many disease especially in meningitis and hemorrhages and for the diagnosis of many malignancy.
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
2. Objectives of the discussion:
• CSF production and circulation
• Normal CSF values and pressures
• Functions of CSF
• CSF Analysis- Biochemical, Microbiological and
Pathological, including disease markers
• Precautions and Contraindications to CSF
analysis/Lumbar puncture
• Hydrocephalus
3. HISTORY
• First report of existence of CSF – 17th century B.C.
• Hippocrates – 4th B.C.
• Galen discovered ventricular cavities – 2 A.D.
• Vesalius – watery humour – 16th centuryA.D.
• Magendie performed first tap of CSF in 1825.
4. Cerebrospinal Fluid (CSF):
•Liquor cerebrospinalis: clear, colorless fluid
•occupies the subarachnoid space and the
ventricular system around and inside the
brain and spinal cord.
•It acts as a "cushion" or buffer for the
cortex, providing a basic mechanical and
immunological protection to the brain inside
the skull.
•It is produced in the choroid plexus.
6. Amount:
•The CSF is produced at a rate of 500 ml/day.
•The brain can contain only 135 to 150 ml
•The CSF turn over is about 3.7 times a day.
7. Nervous System Compartment Volume of CSF (ml)
Cranial Subarachnoid Space 100
Spinal subarachnoid Space 25
Lateral Ventricular Horns 25-30
Third Ventricle 2-3
Fourth Ventricle 2-3
Volumetric distribution of cerebrospinal
fluid
8. Circulation:
•Produced by modified ependymal cells
(approx. 50-70%), remainder is formed
around blood vessels, & along ventricular
walls.
•Circulates from the lateral ventricles to the
Interventricular foramen, Third ventricle,
Cerebral aqueduct, Fourth ventricle, Median
aperture and Lateral apertures, Subarachnoid
space over brain and spinal cord.
•CSF is reabsorbed into venous sinus blood
via arachnoid granulations.
11. CSF Pressures:
•CSF pressure, as measured by lumbar puncture (LP), is
10-18 cmH2O (with the patient lying on the side)
•20-30cmH2O with the patient sitting up.
•In newborns, CSF pressure ranges from 8 to 10 cmH2O.
•When lying down, CSF pressure as estimated by lumbar
puncture is similar to the intracranial pressure.
•There are quantitative differences in the distributions of
a number of proteins in the CSF.
12. Functions:
CSF serves four primary purposes:
•Buoyancy: The actual mass of human brain: 1400 g; net
weight of the brain suspended in CSF: 25 g
•Protection: CSF protects the brain tissue from injury when
jolted or hit.
•Chemical stability: CSF flows throughout the inner
ventricular system in the brain, is absorbed back into the
bloodstream, rinsing the metabolic waste from the central
nervous system through the blood-brain barrier.
•Prevention of brain ischemia
13. Normal Values for Adults (Lumbar CSF)
Opening pressure 50–200 mm H2O CSF (range in literature)
Color Colorless
Turbidity Crystal clear
Mononuclear cells <5 per mm
3
Polymorphonuclear leukocytes 0
Total protein 22–38 mg/dl (mean from literature)
Range 9–58 mg/dl (mean ± 2.0 SD
Glucose 60–80% of blood glucose
14. Reference ranges for CSF constituents
Substance Lower limit Upper limit Unit
Corresponds
to % of that in
blood plasma
RBCs n/a 0/ negative
cells/µL or
cells/mm3
WBCs 0 3
cells/µL
cells/mm3
pH 7.28 7.32 (unitless)
PCO2
44 50 mmHg
5.9 6.7 kPa
PO2
40 44 mmHg
5.3 5.9 kPa
Chloride 115 130[ mmol/L >100%
Glucose
50 80 mg/dL
~60%
2.2, 2.8 3.9, 4.4 mmol/L
Protein 15 40, 45 mg/dL ~1%
15. Reference ranges for ions and other
molecules in CSF
Substance Lower limit Upper limit Unit
Corresponds
to % of that in
plasma
Osmolality 280 300 mmol/L
Sodium 135 150 mmol/L
Potassium 2.6[ 3.0 mmol/L
Calcium 1.00 1.40 mmol/L ~50%
Creatinine 50 110 µmol/L
Phosphorus 0.4 0.6 µmol/L
Urea 3.0 6.5 mmol/L
16. Blood Brain Barrier
• Brain capillaries show no fenestrations or pinocytotic (transportation)
vesicles and have tight junctions that almost fuse adjacent cells. This
anatomy creates the blood-brain barrier (BBB).
• The BBB separates plasma from the interstitial space of the CNS and
affects in a critical fashion the traffic of molecules in and out of the
brain.
• Lipophilic compounds cross the BBB easier than hydrophilic ones do;
small lipophilic molecules diffuse freely.
• Some hydrophilic compounds enter the brain with the help of
transporters;larger molecules enter via receptor-mediated endocytosis.
• The BBB protects the brain from toxic substances but impedes also the
entry of drugs.
• Hypertonic stimuli and chemical substances including glutamate and
certain cytokines can open the BBB.
• HIE and inflammatory mediators produced in sepsis disrupt the BBB.
17. Clarity:
• The normal CSF is crystal clear.
• The occurrence of pleocytosis: usual reason for cloudy fluid.
• 200 white cells/cmm can be present without altering clarity.
• Over 500 white cells/cmm usually produces cloudiness.
• Red cell concentrations between 500 and 6000 per cmm can
cause the fluid to appear cloudy, while concentrations of over
6000 give a grossly bloody appearance.
• A markedly elevated protein can also alter the clarity
• The clarity of the fluid is of little clinical use, except to provide
an immediate indication of abnormality of the CSF. A very
useful point to remember is that a large number of cells can
be present without affecting the clarity.
18. Analysis of Xanthochromic CSF
Technique Compare CSF with a similar volume of water in
an identical tube; look down the longitudinal
axis of the tube, against a white background;
ask the ward clerk to see if there is any
difference in the two tubes.
Pigments seen in subarachnoid hemorrhage (SAH)
Oxyhemoglobin Pink or orange color; released into CSF in 2 hours
after SAH, due to RBC lysis; may be released
within 30 minutes if RBC greater than
150,000/mm
3
; maximum color in 36 hours,
disappears in 7 to 10 days; cerebrospinal fluid
must be examined immediately after the LP,
since oxyhemoglobin can be produced by lysis of
RBC in the test tube.
Bilirubin Produces the yellow pigment, or xanthochromia
of CSF; produced in vivo by the conversion of
free hemoglobin by macrophages and other
leptomeningeal cells; not seen for 10 to 12 hours
after the hemorrhage; reaches a maximum in 48
hours, and persists 2 to 4 hours.
19. Other causes of xanthochromia
Protein Protein over 150 mg/dl produces xanthochroma, the intensity paralleling the amount of
protein
RBCs RBC over 100,000/mm
3
produce xanthochromia as a result of serum brought with them
Jaundice Serum bilirubin of 15 mg/dl produces xanthochromia; lower levels will do so when
elevated protein is present; the level of serum bilirubin that produces xanthochromia
appears to be quite variable
Carotene Hypercarotenemia in food faddists produces xanthochromia
Others Subdural hematomas, trauma, and clots in other locations will produce xanthochromia
WBCs The WBC/RBC ratio is similar to that of the plasma in traumatic taps and fresh SAH; a
few days old SAHwill produce a chemical meningitis, elevating the number of WBC.
Glucose CSF glucose can be decreased (10 to 50 mg/dl) in SAH present 4 to 7 days
Protein Each 1000 RBC min raises CSF protein 1.5 mg/dl
Traumatic
tap
Tubes 1 to 3 show decreasing RBC; supernate is colorless if it is examined within 30
minutes, provided the conditions listed above are not present; on rare occasions
patients with SAH have decreased cells from tubes 1 to 3, perhaps due to layering of
blood in a recumbent patient; the color of the supernate should provide the answer in
this rare event; if there is any doubt, immediately do another lumbar puncture in a
different interspace; abnormal CSF from a traumatic tap can persist at least 5 days, and
even longer.
20. Proteins:
• CSF proteins are derived from serum proteins with the exception of
the trace proteins and some beta globulins.
• Serum proteins enter the CSF by means of pinocytosis.
• Clinical usefulness of CSF proteins is presently limited to the
measurement and characterization of total protein and IgG.
• 3 pathological conditions cause abnormalities of the CSF proteins:
– Increased entry of plasma proteins due to increased
permeability of the blood–brain barrier.
– Local synthesis of proteins within the central nervous system.
Clinical interest is limited to IgG currently.
– Impaired resorption of CSF proteins by the arachnoid villi.
• Elevated CSF total protein is highly suggestive of neurologic disease.
• Total protein over 500 mg/dl is seen in meningitis, cord tumor with
spinal block, and bloody CSF.
• Each 1000 RBC/mm3 raises the CSF protein 1.5 mg/dl.
23. IgG in CSF:
• IgG concentration in the CSF is normally 4.6 ± 1.9 mg/dl.
• It is the principal immunoglobulin in the CSF.
• Local synthesis within the central nervous system occurs in a variety of
inflammatory disorders: multiple sclerosis, neurosyphilis, subacute sclerosing
panencephalitis, progressive rubella encephalitis, viral
meningoencephalitides, sarcoidosis, etc.
• IgG can be characterized by agar gel electrophoresis and isoelectric focusing
for the identification of oligoclonal banding in addition to quantification. Up to
90% of cases of confirmed multiple sclerosis have elevated gamma globulin
and/or oligoclonal bands. Oligoclonal bands represent a qualitative change in
IgG.
• The appearance of oligoclonal bands in the CSF in the absence of similar
bands in the serum is an indication of gamma globulin production in the
central nervous system even when quantified levels of gamma globulin are
normal.
• The difficulty in assessing IgG levels in the CSF lies in distinguishing whether
elevated levels are due to increased permeability of the blood–brain barrier,
or whether there is local synthesis in the central nervous system.
24. Fractionation of CSF Protein
Mechanism of elevated
CSF protein CSF/serum albumin ratio CSF/serum IgG ratio CSF IgG/albumin index
Obstruction to CSF
circulation
Elevated Elevated Normal
Increased blood–CSF
barrier permeability
Elevated Elevated Normal
Increased CNS protein
synthesis
Normal Elevated Elevated
Cerebrospinal fluid (CSF) protein is increased by increased permeability of the blood–CSF barrier or
increased CNS protein synthesis. Concurrent measurement of albumin and IgG in both CSF and serum by
immunochemical methods is useful in distinguishing these two mechanisms. Since albumin is neither
synthesized nor metabolized intrathecally, increased CSF albumin relative to serum albumin reflects loss of
functional integrity of the blood–CSF barrier. Synthesis of immunoglobin does occur in the CNS; therefore,
increased CSF IgG relative to serum reflects either permeability changes or increased CNS synthesis.
Comparing the CSF/serum IgG and CSF serum albumin ratios provides a specific index of local immunoglobin
synthesis since the IgG ratio is corrected for permeability changes.
Local synthesis of IgG occurs in demyelinating and some chronic inflammatory CNS diseases. IgG produced
within the CNS tends to have restricted heterogeneity and can be detected as oligoclonal banding on agar
gel protein electrophoresis. Oligoclonal banding occurs in the same spectrum of diseases as elevated CSF
IgG/albumin index; however, electrophoretic detection is considered a more sensitive marker for multiple
sclerosis.
25. Glucose:
• The usual CSF glucose is 60 to 80% of the plasma glucose.
• Glucose is utilized for energy by cellular elements close to the
CSF; this is the principal means of glucose removal.
• The most common cause of lowered CSF glucose
(hypoglycorrhachia) is meningitis: bacterial, tuberculous, fungal,
amebic, acute syphilitic, chemical, and certain of the viral
meningitides (mumps, herpes simplex, and herpes zoster).
• Lowered CSF glucose occurs in about 15% of SAH, reaching a
nadir 4 to 8 days after the bleed.
• Meningeal carcinomatosis also produces hypoglycorrhachia. A
large variety of tumors have been implicated. Cytologic
examination of the fluid is often the key to diagnosis.
• Other causes of lowered CSF glucose include sarcoidosis,
cysticercosis, trichinosis, and rheumatoid meningitis.
26. LUMBAR PUNCTURE
• Lumbar puncture (LP) is usually a safe procedure.
• Major complications: extremely uncommon, include
– cerebral herniation
– injury to the spinal cord or nerve roots
– hemorrhage
– infection.
• Minor complications: greater frequency, include
– Backache
– post-LP headache
– radicular pain or numbness.
27. Proper positioning of a patient in the lateral decubitus position. Note that the shoulders
and hips are in a vertical plane; the torso is perpendicular to the bed. [From RP Simon
et al (eds): Clinical Neurology, 7th ed. New York, McGraw-Hill, 2009.]
Positioning and site of Lumbar puncture
28. Contraindications to Lumbar Puncture:
• Infection in the skin overlying the access site(A)
• Papilledema
• Bleeding diathesis
• Severe pulmonary disease or respiratory difficulty
• An altered level of consciousness.
• Patients with a focal neurologic deficit.
• A new-onset seizure.
• An immunocompromised state.
31. Description of CSF Types
Fluid type WBC
Predominant
cell tvpr Glucose
Protein
(mg/dl)
Normal <5 All
mononuclear
Normal 40–80
mg/dl or at
least 40% of
the
simultaneous
blood sugar
<50
A 500–20,000 90% PMLs Low in most
cases
100–700
B 25–500 Mononuclear
(PMLs early)
Low but may
be normal
50–500
C 5–1,000 Mononuclear
(PMLs early)
Normal, but
rarely quite low
< 100
32. Differential Diagnosis of Infectious
Causes of CSF Pleocytosis
Treatable by specific antimicrobial agents
• Type A fluid:
– Bacterial meningitis (pneumococcus, meningococcus, hemophilus,
streptococcus, listeria, etc.)
– Ruptured brain abscess
– Amebic meningoencephalitis
• Type B fluid
– Granulomatous meningitis
– Tuberculous
– Fungal
• Type C fluid
– Parameningeal infection
– Brain abscess
– Subdural abscess
– Cerebral epidural abscess
– Cerebral thrombophlebitis
– Spinal epidural abscess
– Otitis/sinusitis
– Retropharyngeal abscess
33. Differential Diagnosis (contd.)
Miscellaneous infections:
• Listeria meningitis, Rickettsial meningitis
• Syphilis
• Leptospirosis
• Cerebral malaria
• Trichinosis
• Toxoplasmosis, Trypanosomiasis
• Toxic encephalopathy (associated with systemic bacterial infection)
• Viral infection (Herpes hominis type I encephalitis)
Not treatable by specific antimicrobial agents:
Type C fluid
• Postinfectious and postvaccinal encephalitis
• Viral meningitis (mumps, coxsackie, echovirus, lymphocytic
choriomeningitis, arboviruses, and others)
34. Differential Diagnosis of Noninfectious
Causes of CSF Pleocytosis
Chemical meningitis
Myelography
Spinal anesthesia
Intrathecal medication
Ingestion of mercury or arsenic
Vasculitis
Subarachnoid hemorrhage
Behcet's syndrome
Lead encephalopathy
Sarcoid (may produce type B CSF)
Tumor (leukemia most common; glucose can drop to zero)
Seizure activity (must diagnose only if other possibilities are ruled out and if
pleocytosis is minimal and rapidly clears)
35. CSF Comparison In Various Infections
Cause Appearance
Polymorpho
nuclear cell
Lymphocyte Protein Glucose
Pyogenic
bacterial
meningitis
Yellowish,
turbid
Markedly
increased
Slightly
increased or
Normal
Markedly
increased
Decreased
Viral
meningitis
Clear fluid
Slightly
increased or
Normal
Markedly
increased
Slightly
increased or
Normal
Normal
Tuberculous
meningitis
Yellowish
and viscous
Slightly
increased or
Normal
Markedly
increased
Increased Decreased
Fungal
meningitis
Yellowish
and viscous
Slightly
increased or
Normal
Markedly
increased
Slightly
increased or
Normal
Normal or
decreased
36. Causes of Brain edema
Vasogenic
Cellular
(cytotoxic) Interstitial (hydrocephalic)
Pathogenesis Increased
capillary
permeability
Cellular
swelling—
glial,
neuronal,
endothelial
Increased brain fluid due to
block of CSF absorption
Location of edema Chiefly white
matter
Gray and
white matter
Chiefly periventricular
white matter in
hydrocephalus
Edema fluid composition Plasma
filtrate
including
plasma
proteins
Increased
intracellular
water and
sodium
Cerebrospinal fluid
Extracellular fluid volume Increased Decreased Increased
Capillary permeability to
large molecules (RISA, insulin)
Increased Normal Normal
radioisotope iodinated (125I) serum albumin (RISA)
37. Causes of Brain edema (contd.)
Vasogenic Cellular (cytotoxic)
Interstitial
(hydrocephalic)
Clinical disorders Brain tumor,
abscess, infarction,
trauma,
hemorrhage, lead
encephalopathy
Hypoxia, hypo-
osmolality due to
water intoxication,
etc.
Obstructive
hydrocephalus
Pseudotumor (?)
Disequilibrium
syndromes
Ischemia Ischemia
Purulent meningitis
(granulocytic
edema)
Purulent meningitis
(granulocytic
edema)
Purulent meningitis
(granulocytic
edema)
Reye's syndrome
EEG changes Focal slowing
common
Generalized slowing EEG often normal
38. Brain Edema: Role of drugs
Vasogenic
Cellular
(cytotoxic)
Interstitial
(hydrocephalic)
Therapeutic
effects
Steroids Beneficial in brain
tumor, abscess
Not effective (?
Reye's syndrome)
Uncertain
effectiveness (?
Pseudotumor, ?
meningitis)
Osmotherapy Reduces volume
of normal brain
tissue only,
acutely
Reduces brain
volume acutely in
hypo-osmolality
Rarely useful
Acetazolamide ? Effect No direct effect Minor usefulness
Furosemide ? Effect No direct effect Minor usefulness
39. CSF Biomarkers
• Alzheimer’s disease (AD):
– Beta amyloid type Aβ42 is decreased probably because it
is deposited in plaques and is not available in a diffusible
form.
– Total-tau (t-tau) and phosphorylated tau (p-tau) are both
increased in AD.
• Creutzfeldt-Jacob disease:
– Elevated CSF 14-3-3 in a patient with progressive dementia
of less than 2 years’ duration is considered a strong
indicator of CJD. A negative 14-3-3 test does not rule out
CJD.
– Total-tau (t-tau) increased.
40. SUMMARY
• General physiology: production, distribution, circulation; normal
pressure/biochemical/cellular values, cause for difference from plasma.
• Pathological changes: Pressure, clarity, colour, proteins (esp.IgG), glucose.
• Obtaining, collecting, analysing and storing a CSF sample.
• CSF types (based on pleocytosis), D/D based on types of CSF.
• CSF picture and comparison in various infectious categories.
• CSF biomarkers
41. REFERENCES:
• Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd
edition.Walker HK, Hall WD, Hurst JW, editors.Boston: Butterworths; 1990.
• PATHOLOGY 425 CEREBROSPINAL FLUID [CSF] at the Department of Pathology and
Laboratory Medicine at the University of British Columbia. By Dr. G.P. Bondy. Retrieved
November 2011
• Normal Reference Range Table from The University of Texas Southwestern Medical
Center at Dallas. Used in Interactive Case Study Companion to Pathologic basis of
disease.
• Department of Chemical Pathology at the Chinese University of Hong Kong, in turn
citing: Roberts WL et al. Reference Information for the Clinical Laboratory. In Tietz
Textbook of Clinical Chemistry and Molecular Diagnostics, 4th edn. Burtis CA, Ashwood
ER and Bruns DE eds. Elsevier Saunders 2006; 2251 – 2318
• Ballabh P, Braun A, Nedergaard M. The blood-brain barrier: an overview. Structure,
regulation, and clinical implications. Neurobiol Dis 2004;16:1-13. PubMed
• Owens T, Bechman I, Engelhardt B. Neurovascular Spaces and the Two Steps to
Neuroinflammation. J Neuropathol Exp Neurol 2008; 67:1113-21. PubMed
• Aluise CD, Sowell RA, Butterfield DA. Peptides and Proteins in Plasma and Cerebrospinal
Fluid as Biomarkers for the Prediction, Diagnosis, and Monitoring of Therapeutic
Efficacy of Alzheimer’s disease. Biochim Biophys Acta 2008;1782:549-58 PubMed.
42.
43. Selected examples of promising molecular markers for
targeted detection
Disease Marker
Glioma IL-13
Breast Cancer HER2
Lung Cancer HER2
Malignant Melanoma 9.2.27
Genitourinary Tumors (Ovarian) HER2
Head and Neck Cancers EGFR
Leukemia CD20, CD52
Lymphoma CD20, CD52