CENTRAL NERVOUS SYSTEM

Introduction: The CNS consists of the brain and spinal cord The brain includes cerebral hemisphere and cerebellum The cerebellum is attached to the back of the brain stem and is located just beneath the cerebral hemisphere The lower brain stem flows into the spinal cord which is the point of exit for nerves and entry for sensory fibres. All the nerves outside the CNS are collectively called the peripheral nervous system.

PHYSIOLOGY AND BIOCHEMISTRY OF THE CNS

The total volume of the CSF in adults is about 150ml(120ml-subarachnoid space, 30ml within the cerebral ventricles) CSF is constantly produced and reabsorbed at the rate of only 500ml/day. This means that the total amount of CSF is replaced every 4-6hrs CSF re-absorption can occur along the entire neuro axis If absorption is impaired(as in meningeal inflammation, bact. Menins or sub. Haemge) CNS pressure and CSF volume both rise. An increase in the size of one component(brain, CSF, blood) leads to a sharp increase in pressure within the system unless there is a corresponding decrease in the volume of one of the other 2 components.

Composition of the CSF

The ionic and molecular composition of CSF differs from that of plasma for some components and is the same for others Changes in serum sodium are followed by corresponding >s in CSF Na. CSF Na(138150mmol/L CSF potassium is however lower than plasma K(2.7-3.9mmol/L). CSF K is maintained within a very narrow conc. range in CSF despite wide fluctuations in plasma values Cl- and Mg are somewhat higher in CSF than in plasma. Cl-(116-127MMOL/l) Mg. 24.4-30.5mg/L HCO-3 is somewhat lower 22.9mmol/L

CSF Glucose
Normally ranges from 450-800mg/L Blood glucose equilibrate only after a long period of about 4hrs, so that CSF glucose at any given time reflects blood glucose levels during the past 4 hrs When a lumbar spinal puncture is perfomed and CSF glucose is determined a simultaneous sample of peripheral blood must also be drawn(esplly in the diagnosis of bacteria or carcinomatous meningitis LP and blood glucose shd be obtained only after patient has fasted for at least 4hrs

CSF Proteins
Originate from serum and reach CSF space by pinocytosis across the capillary endothelium. Following electrophoretic separation ff; % Prealbumin-2-7% Albumin 56-76% Alphaglobulin 2-7% IgG 10-40MG/l IgA 0-0.2mg/L IgM 0-0.6mg/L

Factors Affecting CNS Permeability

Inflammation-can increase the ease of entry of eg. Albumin, penicillin Toxins- e.g. Diodrast increase permeability Adrenal Steroids and Thyroid hormones- help to stabilize the integrity of blood-brain barrier Age- immature nervous system more permeable Mol. Wt- entry inversely prop. to size Protein Binding- highly protein-bound cmps enter CNS much less readily e.g. Phenytoin, Ca. Mg, Bil. Lipid Solubility- Cmps that are highly lipid soluble eg. CO , EOH, Neuroactive drugs readily enter the CNS

Pathological Conditions of the CNS

Coma(state of unconscious)- for eg. If due to severe hypoglycemia-iv. Ad. Dextrose will relieve the coma but important to establish the cause. Intracranial Bleeding- can cause chemical meningitis, blood cells may provoke inflammatory response in the meninges Infections and inflammatory diseases; Parameter to look for :white cell count, glucose and to lesser extend protein conc. In viral meningitis- glucose remain within range, protein usually normal or slightly increased Fungi infections may cause lymphocytosis but glucose level is normal. Bacterial infection shd be searched for on Gram stain and culture Ischemia- inadequate blood supply to a tissue(what?) Stroke- drop in blood flow is accompanied by a rapid in tissue osmolality-600mOsm. Inadequate oxygen and glucose results in high lactic acid from glycolysis which further damages the brain

Pathological Conditions of the CNS

Chronic hypoxia- anaemia, congestive heart failure, pulmonary diseases and changes in Hb that interfere with oxygen binding(e.g. CO poisoning, methemoglobin) are egs. Of conditions associated with chronic insufficiency of cerebral perfusion or oxygenation(Xs lethargy, confusion, dementia etc.) Renal Diseases- RF leads to uremic state and an associated encephalopathy cxs by confusion, delirium and finally coma

Pathological Conditions of the CNS Contd

ENDOCRINE DISORDERS Diabetes-can affect CNS in a number of ways- DKA can result in hypoG, can also cause CNS acidosis and CNS hyperosmolality leading to an influx of fluid into the CNScerebral odema Adrenal Disease- inadequate release of cortisol can affect the brain and cause apathy, depression, fatique etc. several metabolic associated derrangementhypoglycaemia, hypoNa, hyperK, Hypotension can all add insult to the bain Xs glucocorticoids products and steroid assoc. can cause mood disturbances eg. Depression, delusion, hallucination etc. Thyroid Diseases- thyrotoxicosis and hypothyroidsm predictably affect the brain e.g. hypothyroid can cause mental retardation in children. Chronic thyroid insufficiency is associated with depression

Causes of Coma & altered Mental State

CAUSE Alcoholism Hyperosmolar coma DKA Met. Acidosis Hypoglycaemia Hyper/Hypocalcaemia Drugs Systemic metabolic diseases Hepatic Coma, Uremic coma Ishaemic, cardiac, pulmonary Encephalopathy(Epilepsy,Intrcranial haemorrhage Trauma Infections(Bacterial, viral) Psychiatric LABORATORY FINDINGS blood EOH, Met. Acidosis & Ketosis Blood glucose>10,000mg/L blood glucose, ketosis, acidosis, dehydration pH, HCO3, lactic acid blood glucose<500mg/L Changes in calcium leads changes in blood Mg(e.g. Hypocal>Hypomag Presence of drugs in high conc. LFT, serum urea, creatinine, met. Acidosis, tissue hypoxia, lactic acsis Sub levels of anti-epileptic drugs Bloody CSF None Glucose, Protein none

Changes in analytes in CNS Diseases

Disease Glucose Tot.Prot IgG N N N Stroke N Hemoge N Epilepsy N Infection Fung/Bac coma Viral mening.
Hyperosmolar hypoglycaemia

N N

Lactic acid N N N

N N N

N N