Systems Pathology I - Exam 3

Ischemia results in dysfunction in

5-10 seconds

Neuron cell death starts at 5 minutes of

severe ischemia

Reversible injury

swelling of soma and axons

Irreversible injury (neuron cell death)

soma shrinks

"red neuron" - red is dead

Astrocytes

gliosis - scar formation

What takes up space and increases ICP

blood, edema, CSF, tumors

Vasogenic edema

typical extracellular edema

Cytotoxic edema

intracellular edema

hypoxia/ischemia

CSF (hydrocephalus)

increased volume of CSF in ventricular system

**fontanelles allow cranium to expand (age matters)

Congenital hydrocephalus

born with malformation of ventricles

Acquired hydrocephalus (MC)

due to blockage or overproduction

Hydrocephalus Ex vacuo

secondary to loss of brain volume from stroke

Brain herniations due to

increased ICP or Mass effect (tumor)

Subfalcine herniation (falx)

compression of anterior cerebral artery

**contralateral leg weakness

Transtentorial herniation (tentorial cerebeli)

compression of CN III

compression of descending motor fibers on opposite side of herniation

**mydriasis (dilated pupil) and anisocoria (unequal pupils)

**weakness on same side of herniation

**Duret hemorrhage (flame shaped bleeds)

Tonsillar herniation (foramen magnum - MOST SEVERE)

compression of respiratory center and cardiac regulatory center

**Rapidly fatal

Focal cerebral ischemia

stroke (cerebral infarction)

*Ischemic - occlusion by thrombus

*hemorrhagic - vascular tear and bleed

transient ischemic attach (no infarction)

Strokes typically occur in which circulation

middle cerebral circulation

Stroke S/S (FAST)

Face - unilateral weakness

Arms - unilateral weakness

Speech - slurred

Time - to call 911

Ischemic stroke - Embolic occlusion (MC)

heart origin

risks related to heart (MI, arrhythmia)

paradoxical embolism (DVT -> left heart)

Ischemic stroke - Thrombus

atherosclerotic plaque

Lacunar stroke

small vessel ischemic stroke

**impacts deep brain structures (thalamus, basal ganglia)

Types of infarcts

1) ischemic - permanent interuption of blood

**liquefactive necrosis

2) hemorrhagic - temporary interuption of blood

Bell's palsy

CN 7 (facial N) paralysis

**Weakness in 1/2 face INCLUDING forehead

****Strokes do not include forehead weakness

Global cerebral ischemia and hypoxia

global ischemia - shock, rapid drop in BP

global hypoxia - altitude, decreased O2 perfusion, CO

Intracranial hemorrhage is caused by (2)

hypertension and connective tissue disorders (EDS and Marfan)

Which two Intracranial hemorrhages are non-traumatic

primary brain parenchymal hemorrhage

subarachnoid hemorrhage

Which two Intracranial hemorrhages are traumatic

epidural hemorrhage

subdural hemorrhage

Primary brain parenchymal hemorrhage

"micro-bleed" small vessel rupture in parenchyma

**chronic HTN

**60 years old

Subarachnoid hemorrhage

bleed within subarachnoid space

1) Rupture of saccular/berry aneurysm (MC)

**thunderclap headache

**In Circle of willis

2) Arteriovenous malformation (AVM)

**high flow and very dangerous

**S/S - intractable headache, seizures

**MC 10-30 males

Hypertensive encephalopathy

diastolic >130 (increases ICP)

Epidural hemorrhage

artery damage due to mass effect

**skull fracture

Subdural hemorrhage

movement tear of bridging veins

1) infants = shaken baby syndrome (abusive head trauma)

*subdural hemorrhage, cerebral edema, bilateral retinal bleeding*

2) geriatrics = cerebral atrophy

Males ______ likely to die from TBI

3x

Coup injury

cerebral contusion on side of impact

Contrecoup injury

cerebral contusion on opposite side of impact

Concussion (mild TBI)

reversible

ion balance disturbed

NOT shown on MRI or CT

Chronic traumatic encephalopathy (CTE)

S/S - progressive worsening decreased cognition, aggressive, headache

Pathophysiology

- severe or repeated head injuries cause brain changes

- tau proteins tangle (neurofibrillary tangles)

Diffuse axonal injury (DAI)

angular acceleration = whiplash

diffuse white matter damage = rapid stretch of cytoskeleton

Decorticate rigidity

injury between cortex and red nucleus

**brachial flexion and internal rotation of legs

Decerebrate rigidity

injury to brainstem between red nucleus and vestibular

**limbs extended (loss of inhibition of extensive tone)

Neural tube defects are caused by

folate (B9) deficiency

Spina bifida occulta (hidden)

mild, asymptomatic, tuft of hair over lumbars

Meningocele

includes meninges and CSF

Myelomeningocele (MOST SEVERE)

includes Cauda Equina

**damage LMN - impaired motor (flaccid paralysis)

**impaired sensory and bowel/bladder functions

Myelomeningocele is associated with which Chiari malformation

Type II (arnold chiari malformation)

Encephalocele

craniofacial abnormalities

**includes CSF and brain tissue

Anencephaly

common cause of stillbirth

*severely disabled (not compatible with life)

Syringmyelia (syrinx)

CSF filled cyst in central canal of spinal cord

**Adults

**Hydromyelia - extended 4th ventricle (congenital)

**Shawl-like distribution

**compression on crossing spinothalamic tracts

Syringmyelia (syrinx) is associated with which Chiari malformation

Type I

Chiari malformations

Type I = low lying cerebellar tonsils through FM, misshapen posterior fossa, mild and MC (adults)

**5mm

Type II (Arnold Chiari Mal.) = downward extension of cerebellar tonsils and vermis through FM (infants/utero)

What is the most common autoimmune demyelinating disorder in the US

multiple sclerosis

Multiple Sclerosis (MS)

autoimmune demyelinating disorder (Th cells)

**white matter plaques

MC young/middle adult females

S/S:

- spastic weakness (UMN damage)

**optic N lesions (MC initial feature!!)

- SC lesions (sensory and motor impairment)

Wernicke Korsakoff

thiamine (B1) deficiency of CNS

**necrosis of thalamus

Beriberi

thiamine (B1) deficiency of PNS

**Lower extremity paralysis

Cobalamin

B12 deficiency

**cord demyelination (sensory and motor defects)

What disease is the MC cause of dementia

alzheimers

Alzheimer Disease (AD)

Primary risk factor for late onset = 85+ years old

**death by pneumonia

**B-amyloid and Tau tangles

**prominent atrophy of hippocampus and frontal lobe

Parkinson Disease

bradykinesia (loss of dopamine)

pill-rolling tremor

festinating gait

lewy bodies

Lewy body dementia

RAPID progression of dementia in 1 year of motor dysfunction

**lewy bodies in cerebral cortex and substantia nigra

Huntington Disease

30-40 years old

involuntary movement and chorea

autosomal dominant (earlier onset for offspring)

**degeneration of caudate and putamen, frontal lobe

Amyotrophic lateral sclerosis (ALS)

40 year old Males

motor neuron disease spares the CN that move the eye

primary motor cortex (betz cells/UMN)

anterior horn (LMN)

**Rapid progression 2-5 years

**Death by respiratory failure/pneumonia

DOES NOT CAUSE DEMENTIA

Shared features of CNS tumors

headache, seizures, focal neurological dysfunction, increased ICP

Gliomas

1)Astrocytoma**

2) Oligodendroglioma

3) Ependymoma

Astrocytoma (MC adult glioma)

Diffuse - malignant, 30-60 years old, cerebral (frontal)

Pilocytic - benign, cystic, children, cerebellum + SC

Glioblastoma

most aggressive astrocytoma

Oligodendroglioma

adults

30-50 years old

Ependymoma

increased CSF (hydrocephalus)

pediatrics (MC 4 years old)

Medulloblastoma

malignant, cerebellum (small round cells)

pediatric

Primary CNS lymphoma

diffuse large B cell lymphoma

immunosuppressed (AIDS)

Meningioma

90% benign but invasive, arachnoid

adult females

Metastasis

gray/white junction

Tuberous scerosis

autosomal dominant

cortical "tubers"

facial angiofibromas

von Hippel-Lindau disease

autosomal dominant - tumor suppressor mutation

cerebellum

Epidural abscess

cord compression

from sinusitis

Meningitis

inflammation of leptomeninges (arachnoid and pia)

1) Acute pyogenic

2) Aseptic (MC viral)

3) Chronic (TB)

**Kernig and Brudzinski

Fungal encephalitis

rare, MC in immunosuppressed

Polio virus

death via respiratory failure

virus retrograde to ventral/anterior horn

What is a site for edema and WBC diapedesis

postcapillary venules

Endothelial cells vasoreactivity

dilation - NO

constriction - endothelin

Causes of Endothelial trauma

high cholesterol (LDL)

hypertension

diabetes, smoking, ROS, vasculitis

Arterovenous (AV) fistula

artery inappropriately connects to vein

Fibromuscular dysplasia

local thickening of arterial wall causes ischemia

renal and carotid arteries

women

*Renovascular hypertension*

High BP

stretches and ANP released

Low BP

renin-angiotensin system

Hypertension (silent killer)

risk for atherosclerosis, dissection, MI, stroke, renal failure

**Mechanisms - increased vascular tone, decreased Na excretion, age, stress obesity, genetics (African am.)

1) Essential HTN - MC

2) Malignant HTN/hypertensive crisis - >180/120

**papilledema and renal hemorrhage

Phenochromocytoma

episodic spikes in BP

Arteriosclerosis

hardening of arteries

Arterioloscerosis

1) Hyaline - benign HTN or diabetes (pink)

2) Hyperplastic - severe malignant HTN (onionskin)

**Possible kidney failure

Monckeberg Medical Sclerosis

incidental finding of calsified arteries

elderly

Most arteriosclerosis is

atherosclerosis

What is the #1 cause of morbitity

atherosclerosis

Atherosclerosis (plaques)

causes ischemia and may rupture -> MI

weakens tunica media -> aneurism

Foam cells

macrophages and lipids

Vulnerable plaque

thin fibrous cap

high levels of inflammation

Arteries most at risk of atherosclerosis

abdominal aorta, coronary, carotid, iliofemoral

branch points

hemodynamic stress

Risk factors for atherosclerosis

too few HDL, too much LDL

**apolipoprotein (more sensitive marker than LDL)

MI risk factors

hyperlipidemia, HTN, smoking, diabetes

**2 - 4x risk

**3 - 7x risk

Aneurysms

Risk factors - HTN, atherosclerosis, Marfans/EDS

True aneurysm includes

all 3 tunics