Essentials of Pathophysiology
CHAPTER 37
DISORDERS OF BRAIN FUNCTION
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
F
T
F
F
T
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.

PRE LECTURE QUIZ
Glasgow

__________________ is defined as an abnormal
increase in cerebrospinal fluid (CSF) volume in any
part or all of the ventricular system.
Hydrocephalus  The ______________ Coma Scale is a method for
assessing level of consciousness in persons with
brain injury.
Meningitis

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.
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 acids
d. Proteins and monosaccharides
ANSWER
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.
b.
HYPOXIA AND ISCHEMIA

Hypoxia causes ATP depletion or “power failure”

Aerobic metabolism stops  less ATP is produced
 Na+/K+
º

ATPase cannot run fast enough
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
 Arteries

pressure greater than arterial blood
collapse; blood flow to brain cut off
Brain swelling
 Vasogenic:
 Cytotoxic:
extracellular fluid
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
False
Rationale: 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
Middle cerebral artery
Internal carotid arteries
branch into:
 Anterior cerebral arteries
Anterior
º Medial and superior
cerebral
surfaces of brain;
artery
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
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
Posterior
cerebral
artery
They supply the
medulla, pons,
cerebellum,
midbrain, occipital
lobes, temporal
lobes, thalamus
Basilar
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 arteries
b. Cerebral arteries
c. Basilar arteries
d. Circle of Willis
ANSWER
Circle of Willis
Rationale: 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.
d.
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. Partial
b. Secondarily generalized
c. Generalized
d. All of the above
ANSWER
Partial
Rationale: 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.
a.
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
amyloid
precursor
protein
normally
soluble
protein
fragments
cleared
away
in
Alzheimer disease
amyloid b
stick together
to form fibrils
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. Alzheimer
b. Microinfarcts
c. Vitamin B12 deficiency
d. Inherited
ANSWER
Microinfarcts
Rationale: 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.
b.