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CHAPTER 37
DISORDERS OF BRAIN FUNCTION
Essentials of Pathophysiology
RESEARCH NEWS
Migraines Increase Stroke Risk
November 18, 2009
Pooling results from 21 studies, involving 622,381 men and women, researchers at Johns Hopkins Univ. have affirmed that migraine headaches are associated with more than two-fold higher chances of the most common kind of stroke: those occurring when blood supply to the brain is suddenly cut off by the buildup of plaque or a blood clot.
PRE LECTURE QUIZ Cerebral edema, or brain swelling, is
characterized by a decrease in volume secondary to an abnormal fluid accumulation.
The brain tissue and interstitial fluid represent the majority of the skull content.
Concussions are listed under the category of focal brain injuries.
All seizure events are related to epilepsy. Alzheimer disease is characterized by
cortical atrophy and loss of neurons.
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PRE LECTURE QUIZ __________________ is defined as an abnormal
increase in cerebrospinal fluid (CSF) volume in any part or all of the ventricular system.
The ______________ Coma Scale is a method for assessing level of consciousness in persons with brain injury.
A ______________ is an acute focal neurologic deficit from an interruption of blood flow in a cerebral vessel due to thrombi or emboli or to bleeding into the brain.
______________ is an inflammation of the pia mater, the arachnoid, and the CSF-filled space that can spread rapidly because of CSF circulation around the brain and spinal cord.
A ___________ represents the clinical manifestations of an abnormal, uncontrolled electrical discharge from a group of neurons in the cerebral cortex.
Glasgow
Hydrocephalus
Meningitis
Seizure
stroke
GLASGOW COMA SCALE scale that is used to assess the severity of a brain
injury values from 3 to 15 obtained by summing the
ratings assigned to three variables depending on whether and how the patient
responds to certain standard stimuli by opening the eyes, giving a verbal response, and giving a motor response,
a low score (as 3 to 5) indicates a poor chance of recovery
a high score (as 8 to 15) indicates a good chance of recovery
QUESTION
What two substances are needed by the mitochondria in order to produce ATP?
a. O2 and CO2
b. Glucose and O2
c. Glucose and fatty acidsd. Proteins and monosaccharides
ANSWER
b. Glucose and O2
Rationale: Glucose and oxygen are necessary for ATP production. Without ATP, no physiologic work can be done—the cells, and eventually the organism, will die. When oxygen is not available, anaerobic pathways are used, creating lactic acid that also damages the cell.
HYPOXIA AND ISCHEMIA
Hypoxia causes ATP depletion or “power failure”
Aerobic metabolism stops less ATP is produced
Na+/K+ ATPase cannot run fast enough
º Cell swells up with water
Anaerobic metabolism used lactic acid produced
Acid damages cell membranes, intracellular structures, and DNA
HYPOXIA AND ISCHEMIA (CONT.)
Ischemia also interferes with: Delivery of energy stores
(e.g., glucose) Damage to blood vessels
Vasomotor paralysis Vasoconstriction
Changes in blood Desaturation Clotting Sludging
CALCIUM CASCADE
Ischemia depolarization
Depolarization glutamate release
Glutamate calcium cascade
Calcium influx depolarization
the predominant molecular Receptor for controlling synaptic plasticity and memory function
INTRACRANIAL PRESSURE (ICP) Compartment syndrome in the skull
Intracranial pressure greater than arterial blood pressure
Arteries collapse; blood flow to brain cut off
Brain swelling Vasogenic: extracellular fluid Cytotoxic: intracellular fluid
Hydrocephalus: cerebrospinal fluid Tumors
BRAIN HERNIATION Increased
intracranial pressure pushes the brain out of position
Brain tissue is compressed into
the center of the brain (2),
against bone (4) or against rigid folds
of the dura mater (1, 3)
Compression of the oculomotor nerve is an early sign
TRAUMATIC BRAIN INJURY
Primary injuries—due to impact Microscopic damage: concussion,
diffuse axonal injury Contusions
Secondary injuries—due to: Hemorrhage Ischemia Infection Increased intracranial pressure
QUESTION
Tell whether the following statement is true or false.
Increased ICP results in primary brain injury.
ANSWER
FalseRationale: Increased pressure in the
brain leads to secondary brain injury (there’s nowhere for the pressure to be released because the brain is encased in bone). Primary brain injury is caused by trauma.
HEMATOMA—BROKEN BLOOD VESSELS
Epidural space: meningeal arteries
Rapid bleeding; unconsciousness may be followed by brief lucid period
Dura mater Subdural space:
bridging veins Slower bleeding;
gradual development over days or weeks
CEREBRAL BLOOD FLOW Carotid arteries branch
into: External carotid – facial Internal carotid - brain
Internal carotid arteries branch into: Anterior cerebral
arteriesº Medial and superior
surfaces of brain; frontal lobes
Middle cerebral arteries
º Lateral surfaces of brain: face and arm motor and sensory cortexes, optic radiations, speech centers
Brain (lateral view)
Internal carotid artery
Middle cerebral artery
Anterior cerebral artery
CEREBRAL BLOOD FLOW (CONT.) The basilar artery
runs up to the back of the brain It splits to form
the two posterior cerebral arteries
º They supply the medulla, pons, cerebellum, midbrain, occipital lobes, temporal lobes, thalamus
Basilar artery
Posterior cerebral artery
CIRCLE OF WILLIS Anterior communicating
artery Connects right and left
anterior cerebral arteries
Blood from one carotid can cross over to supply the other side of the brain
Posterior communicating arteries Connect the posterior
and middle cerebral arteries
Blood from the basilar artery can run forward and supply the front of the brain
Brain: ventral view
QUESTION
Which of the following blood vessels ensures collateral circulation in the brain?
a. Internal carotid arteriesb. Cerebral arteriesc. Basilar arteriesd. Circle of Willis
ANSWER
d. Circle of WillisRationale: The circle of Willis connects
the right and left anterior cerebral arteries and the posterior and middle cerebral arteries. Blood from one carotid can cross over to supply the other side of the brain; blood from the basilar artery can run forward and supply the front of the brain.
STROKE
Stroke = “brain attack”
Ischemic stroke
Large vessel (thrombotic)
Small vessel (lacunar infarct- occlusion of one of the penetrating arteries that provides blood to the brain's deep structures)
Cardiogenic embolic
Hemorrhagic stroke
Transient ischemic attacks (“brain angina”)
EXCITOTOXICITY
Neuron firing releases glutamate
Causes neighboring neurons to fire
Spreading injury across the ischemic area
DISCUSSION
Mr. X has cor pulmonale. Mr. Y has a left ventricular aneurysm.
Questions:
Which of them is more likely to have a stroke?
Which is more likely to have a pulmonary embolism?
ANEURYSMAL SUBARACHNOID HEMORRHAGE
Aneurysm Sudden-onset headache with nausea,
vomiting, dizziness Hemorrhage
Sudden severe headache, neck stiffness, photophobia, vision and motor problems
Complications Rebleeding, vasospasm and ischemia,
hydrocephalus, hypothalamus dysfunction, seizures
BRAIN TUMORS
Focal disturbances
Dysfunction of particular brain areas
Seizures, hallucinations, weakness or palsies in specific areas, sensory deficits
Generalized disturbances
Increased intracranial pressure: headache, vomiting, visual problems
SEIZURES
Spontaneous nerve firing Provoked seizures
Fever Electrolyte imbalances (hypocalcemia,
alkalosis) Hypoglycemia CNS infection or damage
Unprovoked seizures: cause unknown
EPILEPTIC SYNDROMES Partial seizures
Begin in one cerebral hemisphere Secondarily generalized seizures
Begin in one hemisphere and spread to other
Generalized seizures Involve both hemispheres
KINDS OF SEIZURES
Absence (petit mal): disturbances in consciousness
Atonic: loss of muscle tone Myoclonic: muscles contract Tonic-clonic (grand mal): muscle
contraction and loss of consciousness Generalized convulsive status
epilepticus: seizures continue without recovery between them
QUESTION
Which type of seizure affects only one cerebral hemisphere?
a. Partialb. Secondarily generalizedc. Generalizedd. All of the above
ANSWER
a. PartialRationale: Partial seizures affect one
cerebral hemisphere; secondarily generalized seizures begin in one hemisphere and then spread to the other side; generalized seizures involve both hemispheres.
DEMENTIAS
Many dementias are associated with abnormal inclusions in the brain
Alzheimer disease: amyloid plaques
Pick disease: Pick bodies
Prion diseases: prion proteins
Creutzfeldt-Jakob disease
ALZHEIMER DISEASE (50 – 70 % OF DEMENTIA)
Amyloid-beta protein-forming plaques
Neurofibrillary tangles
Decreased acetylcholine production
ALZHEIMER DISEASE
Characterized by loss of neurons and ventricular enlargement
ALZHEIMER DISEASE LOSS OF FUNCTION Normal function Alzheimer function
ALZHEIMER DISEASE
A healthy neuron (top right) contrasted with a damaged neuron (note its shriveled state and the presence around the nucleus of neurofibrillary tangles) Tom Dolan, UK Medical Illustrator
ALZHEIMER DISEASE
in Alzheimer disease
normally
amyloid precursor protein
amyloid b
stick together to form fibrils
soluble protein
fragments
cleared away
amyloid plaques
STAGES OF ALZHEIMER DISEASE
First: short-term memory loss
Second: confusional stage
Disorientation, lack of insight, impaired hygiene and language use, sundown syndrome
Third: incontinence, inability to recognize family and friends
OTHER CAUSES OF DEMENTIA
Microinfarcts: vascular dementia
Vitamin B12 deficiency: Wernicke-Korsakoff syndrome
Inherited atrophy of brain structure: Huntington disease
QUESTION
Which cause of dementia is vascular in nature?
a. Alzheimerb. Microinfarctsc. Vitamin B12 deficiency
d. Inherited
ANSWER
b. MicroinfarctsRationale: Small infarctions cause blood
flow to be cut off to certain areas of the brain, causing tissue death. Depending on the extent of the infarctions, the dementia may be more or less severe.