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.