Pathophysiology of the Nervous System PDF

Physiology & Pathophysiology MD 303 Clinical pharmacy program Level 2  Disorders of the nervous system Disorders of neural function (Those conditions that affect the brain, spinal cord and associated nerves) 1- Stroke 2- CNS infection 3- Epilepsy 4- Headache Dege...

Physiology & Pathophysiology MD 303 Clinical pharmacy program Level 2  Disorders of the nervous system Disorders of neural function (Those conditions that affect the brain, spinal cord and associated nerves) 1- Stroke 2- CNS infection 3- Epilepsy 4- Headache Degenerative disorders of the brain and CNS (Those conditions associated with progressive loss of neurons and nervous function) 1- Parkinson’s disease 2- Alzheimer’s disease 3- Huntington’s disease 4- Amyotrophic lateral sclerosis 5- Multiple sclerosis  Stroke Strokes are also referred to as cerebral vascular accidents (CVAs). “Occlusive” or “Ischemic” stroke, the most common form of stroke (87%), which is caused by a blockage of blood flow to the brain. May result from an embolism that lodges in the cerebral vasculature from a thrombus that forms in situ. Complete occlusion of cerebral blood vessels will lead to injury and death of neuronal tissue. Transient ischemic attacks (TIAs) or “mini-strokes” lasting several minutes may also occur as a result of a developing thrombus or transient occlusion by thrombotic particle. Hemorrhagic stroke caused by bleeding into the brain as a result of a ruptured cerebral aneurysm or damage to blood vessels. Risk factors for stroke  CNS infections Infections of the CNS may be bacterial or viral in origin and target Meninges ……………. (meningitis) Brain tissue …………..(encephalitis) Spinal cord ……………(myelitis) Bacterial meningitis is a common CNS infection. Acute meningitis caused by Streptococcus pneumoniae, Hemophilus influenzae, and Nisseria meningitides. Chronic meningitis caused by syphilis, Lyme disease or advanced tuberculosis and may also affect adjacent brain tissue. Most cases of encephalitis are viral in origin and may be caused by viruses such as herpes simplex virus, West Nile virus, arborvirus, and rabies virus.  Epilepsy A disease that is characterized by uncontrolled seizure activity. There are several possible mechanisms by which it may occur:  Imbalance between inhibitory CNS neurotransmitters such as gamma-aminobutyric acid (GABA) and excitatory amino acids such as glutamate (such that levels of the inhibitory neurotransmitters are decreased, whereas levels of excitatory neurotransmitters are increased).  Abnormal activity of CNS ion channels (Ca++, K+, Na+) leads to altered resting membrane potential or abnormal depolarizations  Type of seizures The two main classifications of seizures are focal seizures and generalized seizures. 1. Focal seizures Focal seizures occur in a specific area (foci) of the brain. Focal seizures are further divided into two subcategories based on the presentation of the seizure: Simple partial seizure: No loss of consciousness, patients are fully aware the seizure is occurring. Symptoms depend upon the region of the brain affected by the seizure and may include sensory disturbances (altered sensations, tastes, smells, vision), motor disturbances (abnormal movements on the contralateral side), autonomic disturbances (flushing, diaphoresis, tachycardia). Complex partial seizure: Patients exhibit impaired consciousness Often referred to as psychomotor seizures to reflect the motor and psychic manifestations Symptoms may include automatisms that are repetitive behaviors such as hand rubbing, swallowing, grimacing or walking in circles. Complex visual, and auditory hallucinations may occur. Patients often report a feeling of déjà vu.  Type of seizures 2. Generalized seizures The most common form of seizure is a generalized seizure that involves both lobes of the cerebral cortex. primary generalized starts as seizure activity that involves the entire cerebral cortex. secondary generalized starts as a focal seizure that has spread throughout the cerebral cortex. Generalized seizures are subdivided into several classifications: tonic-clonic, Myoclonic, Clonic, tonic, atonic, and absence. Tonic- Previously referred to as grand mal seizures Clonic Involves uncontrolled stiffening of muscles (tonic) followed by alternating contraction and relaxation seizure (clonic) Patients are unconscious during the seizure. They may lose their bladder control and bite their tongue As a result of the widespread seizure activity, the brain may become depleted in oxygen and nutrients. During the period after the seizure (postictal stage), patients often sleep for several hours and may experience a period of confusion after awakening. Myoclonic Presents as sudden, brief twitches or jerks of arm and leg muscles. May be generalized in terms of presentation or limited to muscles of face, extremities or trunk  Type of seizures Clonic Associated with rhythmic jerking muscle movements. May begin with a loss of consciousness and hypotonia Tonic Sudden stiffening of muscles in the back, arms and legs that may cause patients to fall to the ground Atonic Sudden loss of muscle tone that may cause patient to droop or fall to the ground. Also known as “drop” seizures Absence Previously called petit mal seizures Occur primarily in children and may resolve in adulthood Characterized by repeated periods of blank staring coupled with automatisms such as lip smacking or rapid movement of the eyelids Patients appear awake but are unresponsive during the seizure Each seizure lasts only a few seconds but they may occur repeatedly throughout the day.  Headache The vast majority of headaches are benign. The presentation of pain may be unilateral or bilateral. Pain may be dull and throbbing or sharp and radiating. The duration of a typical headache may also vary greatly. Simple headaches may be the result of *stress *excess alcohol consumption *smoking *fatigue The etiology of more complex headaches remains poorly understood and may be related to *abnormal nerve activity *regional alterations in brain blood flow *inappropriate release of pain transmitting neuropeptides. Headaches may be classified into two main categories: primary headaches and secondary headaches.  Primary headaches Cluster headache Migraine headache Tension headache Occur in cyclical Intense throbbing or A very common form of patterns or pulsing sensation in one mild-to-moderate “clusters” area of the head. headache that is often Occur more commonly Often accompanied by severe described as a tight in men than women. nausea and vomiting, as band around the head. Intense pain around well as sensitivity to Pain is often dull and one eye or in a light. diffuse. region of the head Attacks may last hours to Most commonly that often wakes days. triggered by stress. individuals in the Migraine headaches may be Tension headaches were middle of the preceded an aura that thought to be related night. includes sensory symptoms to muscle tension in Clusters of such as flashing lights or the head and neck frequent headaches tingling in extremity. region; however, may be followed by research has not Certain foods or odors may long periods with supported this idea. act as “triggers” for no headaches. migraines and should be avoided.  Secondary headaches Secondary headaches may result from A serious brain conditions such as A more benign processes such as  Brain cancer  Sinus infection  Brain aneurysm  Influenza  Encephalitis  Ear infections  Concussion  Excess alcohol consumption  Hemorrhagic stroke  Parkinson’s disease A condition that was characterized by involuntary tremors, muscle weakness, abnormal gait and difficulty walking. Parkinson’s disease is a progressive neurologic condition that results from destruction of dopaminergic neurons in the substantia nigra and basal ganglia regions of the brain. These areas play an important role in both controlling and initiating voluntary movements. The basal ganglia also plays a role in regulating activity of the autonomic nervous system. Parkinson’s disease develops as a result of complex interactions between genes and environmental factors.  Alzheimer’s disease Alzheimer’s disease is the leading cause of dementia in elderly patients. The risk of developing Alzheimer’s increases proportionally with increasing age. Etiology of Alzheimer’s disease Alzheimer’s disease is associated with a marked atrophy of neurons in the cerebral cortex that is accompanied by enlargement of the brain ventricles. Areas of the cortex affected include those involved in speech, memory, and cognition. Decreased levels of the neurotransmitter acetylcholine occur as a result of reduced neuronal synthesis. Two pathologic “hallmarks” found in the brains of patients with Alzheimer’s disease are The presence of beta amyloid plaques (formed from accumulations of a brain protein called amyloid beta). The presence of neurofibrillary tangles (formed from accumulations of a protein called tau).  Huntington’s disease Huntington’s disease is an inherited disorder that is characterized by a progressive destruction of brain neurons. The disease is inherited as an autosomal recessive disorder. Most patients begin to exhibit symptoms in their 30s to 40s. The condition affects a broad range of CNS neurons and, as a result, the disease can affect voluntary movements, cognitive function, and emotional stability. Although the physiologic function of the normal huntingtin protein is uncertain, the abnormal huntingtin protein is larger in size than the normal protein and may not be properly processed or degraded within the CNS neurons. Accumulation of abnormal huntingtin protein fragments may alter neuronal function and lead to cell death.  Amyotrophic lateral sclerosis ALS is a progressive neurologic condition that primarily affects motor neurons in the anterior (motor) horns of the spinal cord. The term “amyotrophy” refers to the degeneration and shrinkage of motor neurons and subsequent wasting of skeletal muscle that occurs as a result of nervous innervation. The “sclerosis” in the name refers to the hardened or scarred appearance of the neurons at autopsy. Although the exact cause of ALS is uncertain, 5%–10% of cases are inherited. The remaining cases may be possibly related to inappropriate immune response, excess levels of excitatory neurotransmitters such as glutamate, or the accumulation of abnormal proteins in nerve cells. There is currently no cure for ALS, and the average life expectancy after diagnosis is generally 3–5 years. The most common cause of death for patients with ALS is respiratory failure.  Multiple sclerosis Multiple sclerosis (MS) is a progressive neurologic disease characterized by autoimmune demyelination of CNS neurons. Areas of neuronal demyelination are called “plaques.” Loss of the myelin sheath slows and impairs normal electrical conduction in myelinated neurons. Because MS can affect multiple types of CNS neurons, symptoms may include sensory, motor and autonomic dysfunction. Although the exact cause of MS is unknown, there is a very strong autoimmune component with the patient’s immune system destroying the myelin sheath covering nerve fibers. The majority of patients who are first diagnosed with MS present with a relapsing-remitting form of the disease in which they experience episodes of worsening symptoms that develop over days to weeks but usually resolve spontaneously. The course of the disease between exacerbations is stable. Approximately 60%–70% of patients with the relapsing-remitting form of MS will go on to develop a secondary- progressive form of MS that is characterized by a steady progression of symptoms with or without superimposed acute relapses.