1. Chapter 37 Disorders of Brain Function
Essentials of Pathophysiology
Chapter 37 Disorders of Brain Function

2. Research News Migraines Increase Stroke Risk
November 18, 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.

3. Pre lecture quiz 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.

4. Pre lecture quiz Glasgow Hydrocephalus Meningitis Seizure stroke
__________________ 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.

5. 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

6. Question
What two substances are needed by the mitochondria in order to produce ATP?
O2 and CO2
Glucose and O2
Glucose and fatty acids
Proteins and monosaccharides

7. 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.

8. Hypoxia and Ischemia Hypoxia causes ATP depletion or “power failure”
Aerobic metabolism stops  less ATP is produced
Na+/K+ ATPase cannot run fast enough
Cell swells up with water
Anaerobic metabolism used  lactic acid produced
Acid damages cell membranes, intracellular structures, and DNA

9. 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

10. Calcium Cascade Ischemia  depolarization
Depolarization  glutamate release
Glutamate  calcium cascade
Calcium influx  depolarization
the predominant molecular Receptor for controlling synaptic plasticity and memory function

11. 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

12. 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

13. 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

14. Question
Tell whether the following statement is true or false. Increased ICP results in primary brain injury.

15. 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.

16. 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

17. Cerebral Blood Flow Carotid arteries branch into:
External carotid – facial
Internal carotid - brain
Internal carotid arteries branch into:
Anterior cerebral arteries
Medial and superior surfaces of brain; frontal lobes
Middle cerebral arteries
Lateral surfaces of brain: face and arm motor and sensory cortexes, optic radiations, speech centers
Middle cerebral artery
Anterior cerebral artery
Brain (lateral view)
Internal carotid artery

18. Cerebral Blood Flow (cont.)
The basilar artery runs up to the back of the brain
It splits to form the two posterior cerebral arteries
They supply the medulla, pons, cerebellum, midbrain, occipital lobes, temporal lobes, thalamus
Posterior cerebral artery
Basilar artery

19. 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

20. Question
Which of the following blood vessels ensures collateral circulation in the brain?
Internal carotid arteries
Cerebral arteries
Basilar arteries
Circle of Willis

21. 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.

22. Stroke Stroke = “brain attack” Ischemic stroke Hemorrhagic 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”)

23. Excitotoxicity Neuron firing releases glutamate
Causes neighboring neurons to fire
Spreading injury across the ischemic area

24. 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?

25. Aneurysmal Subarachnoid Hemorrhage
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

26. 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

27. Seizures Spontaneous nerve firing Provoked seizures Fever
Electrolyte imbalances (hypocalcemia, alkalosis)
Hypoglycemia
CNS infection or damage
Unprovoked seizures: cause unknown

28. 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

29. 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

30. Question
Which type of seizure affects only one cerebral hemisphere?
Partial
Secondarily generalized
Generalized
All of the above

31. 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.

32. 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

33. Alzheimer Disease (50 – 70 % of Dementia)
Amyloid-beta protein-forming plaques
Neurofibrillary tangles
Decreased acetylcholine production

34. Alzheimer Disease
Characterized by loss of neurons and ventricular enlargement

35. Alzheimer Disease Loss of function
Normal function Alzheimer function

36. Alzheimer Disease

37. 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

38. Alzheimer Disease amyloid precursor protein normally soluble amyloid b
fragments
stick together
to form fibrils
cleared
away
amyloid
plaques

39. 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

40. Other Causes of Dementia
Microinfarcts: vascular dementia
Vitamin B12 deficiency: Wernicke-Korsakoff syndrome
Inherited atrophy of brain structure: Huntington disease

41. Question
Which cause of dementia is vascular in nature?
Alzheimer
Microinfarcts
Vitamin B12 deficiency
Inherited

42. 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.