Exam 3

Front 1

The 2010 economic impact of cancer in the
US was $125 billion

Estimate for 2020 is $200 billion

Back 1

*

Front 2

BRCA1 and BRCA2 function in the same multiprotein complex as tumor suppressors

Back 2

*

Front 3

May help maintain genomic integrity by promoting repair of DNA double strand breaks that result from damage.

Back 3

*

Front 4

Evidence also suggests the BBRCA may play a role in transcriptional regulation, chromatin remodeling, and stopping the cell cycle at the G1/S checkpoint for repair.

Back 4

*

Front 5

A woman with harmful mutations in BRCA1 or 2 is five times more likely to get breast cancer. Genetic tests are available to check for BRCA1 and BRCA2 mutations.

Back 5

Increased surveillance, prophylactic surgery, avoidance of risk factors, chemoprevention { what happens when the mutations are found}

Front 6

Accounts for 1/2 of the familial breast cancers

Back 6

Harmful BRCA1 mutations

Front 7

Confers high risk for ovarian cancer as well

Back 7

Harmful BRCA1 mutations

Front 8

May also predispose men to pancreatic cancer, prostate cancer, breast cancer and colon cancer

Back 8

Harmful BRCA1 mutations

Front 9

Regulation of estrogen receptor activity

Back 9

Harmful BRCA1 mutations

Front 10

Accounts for 1/3 of the familial breast cancers

Back 10

Harmful BRCA2 mutations

Front 11

Confers high risk for ovarian cancer as well (but not as high as BRCA1)

Back 11

Harmful BRCA2 mutations

Front 12

Confers high risk for male breast cancer (10-20% of all cases have BRCA2 mutations)

Back 12

Harmful BRCA2 mutations

Front 13

May also predispose to malignant melanoma, prostate, pancreatic, gall bladder, bile duct and stomach cancer

Back 13

Harmful BRCA2 mutations

Front 14

Cadherins exhibit homotypic bonding

Back 14

*

Front 15

While primary tumors at various sites have a preferential type of metastatic spread, the precise localization of metastases cannot be predicted with certainty for any type of cancer.

Back 15

*

Front 16

Hepatitis B (HBV
Hepatitis C (HCV)

Epstein-Barr (EBV)
Herpes (HHV8)

Papilloma (HPV-16, -18, -31, -33)

Back 16

*Viral causes of cancer:

Front 17

Hepatocellular carcinoma is 200x more
likely after chronic liver inflammation

Back 17

*Hepatitis B (HBV
Hepatitis C (HCV)

Front 18

Epstein-Barr (EBV)

Back 18

*Burkitt’s lymphoma

Front 19

Herpes (HHV8)

Back 19

*Kaposi’s sarcoma

Front 20

Papilloma (HPV-16, -18, -31, -33)

Back 20

*cervical & anal(Gardasil)

Front 21

HTLV

Back 21

leukemia, lymphoma

Front 22

Any immunocompromised person is at greater
risk of developing a viral caused cancer

Back 22

*

Front 23

Main known risk for cervical cancer is infection with the “high-risk” or cancer-associated human papillomaviruses (HPVs)

Back 23

*

Front 24

These HPVs encode E6, a protein that binds p53 (a tumor suppressor protein) and inactivates it.

Back 24

*

Front 25

Essentially leads to loss-of-function (loss of tumor suppression) without mutating the p53 gene

Back 25

*

Front 26

Helicobacter pylori

Back 26

Bacterial causes of cancer:

Front 27

Helicobacter pylori

Back 27

gastric carcinoma B cell lymphoma of stomach

Front 28

Bacteria associated with cancer:

Back 28

Salmonella typhi

Streptococcus bovis

Chlamydia pneumoniae

Front 29

Salmonella typhi

Back 29

gallbladder cancer

Front 30

Streptococcus bovis

Back 30

colorectal cancer

Front 31

Chlamydia pneumoniae

Back 31

lung cancer

Front 32

Any immunocompromised person is at greater
risk of developing a bacteria caused cancer

Back 32

*

Front 33

Aflatoxin is produced by molds in the aspergillus family. The toxin is a
known human carcinogen causing liver cancer.

Back 33

*

Front 34

Chronic inflammation: contributing factor in some cancers

Back 34

*

Front 35

Ulcerative colitis

Back 35

30x more likely to have colon cancer

Front 36

Hepatitis B & C chronic liver inflammation

Back 36

risk of liver cancer

Front 37

activation of an oncogenic transcription factor known as STAT3, IL-6, & TNFα

Back 37

*

Front 38

Asthma chronic respiratory

Back 38

risk of lung cancer

Front 39

COX-2 inhibitors (aspirin, ibuprofen, etc.) protect against colon cancer
by decreasing inflammation.

Back 39

*

Front 40

Cancer cells secrete IL-8, (& other proinflammatory cytokines) which increases
inflammation, with its accompanying “growth factors”, angiogenic factors,
tissue breakdown, etc.

Back 40

Chronic activation of the immune system promotes:
cancer growth, angiogenesis, and cancer progression:
in situ---------->invasive ------> metastatic

Front 41

Selective growth of antigen-negative variants
Loss of or reduced expression of MHC molecules
Immunosuppression
Antigen Masking
Apoptosis of cytotoxic T-cells (natural killer cells)

Back 41

Immune Evasion by Tumor Cells

Front 42

- Virtually all common types of cancers can occur in this form

Back 42

Familial Cancers

Front 43

Autosomal dominant Inherited Cancer Syndromes

Back 43

Childhood Retinoblastoma
Familial adenomatous polyposis
Li-Fraumeni Syndrome -

Front 44

- About 40% of retinoblastoma cases are hereditary. In inherited retinoblastoma, one mutation in a tumor suppressor gene (RB) located on chromosome #13 is inherited from a parent, and a second mutation occurs during the development of the retina.

Back 44

Childhood Retinoblastoma

Front 45

- When this condition results from mutations in the APC gene (tumor suppressor), it is inherited in an autosomal dominant pattern, which means one copy of the altered gene is sufficient to cause the disorder.

Back 45

Familial adenomatous polyposis

Front 46

Persons with LFS (germline mutation of p53) are at risk for a wide range of malignancies, with particularly high occurrences of breast cancer, brain tumors, acute leukemia, soft tissue sarcomas, bone sarcomas, and adrenal cortical carcinoma.

Back 46

Li-Fraumeni Syndrome -

Front 47

Nonhereditary Predisposing Conditions

Back 47

-Regenerative, hyperplastic and dysplastic cell proliferation
-Chronic Inflammation
-Precancerous Conditions

Front 48

Endometrial hyperplasia
Cervival dysplasia
Bronchial mucosal metaplasia and dysplasia

Back 48

Regenerative, hyperplastic and dysplastic cell proliferation

Front 49

Chronic inflammatory disease of GI tract

Back 49

Chronic Inflammation

Front 50

Solar keratosis (abnormal keratin growth) of skin
Ulcerative colitis – a form of inflammatory bowel disease

Back 50

Precancerous Conditions

Front 51

Changes in organ function

Back 51

Malignant tumors cause organ failure
Benign tumors may cause over-secretion

Front 52

Benign tumors may cause over-secretion

Back 52

(Benign pituitary adenomas)

Front 53

Physical effects of tumors -

Back 53

compression of nerves or veins, intestinal obstruction

Front 54

Tissue Breakdown -

Back 54

E.g., protein wasting (cachexia), bone breakdown

Front 55

when anti-cancer antibodies or T cells mistakenly attack normal cells .

Back 55

Paraneoplastic syndrome–

Front 56

Common in lung, ovarian, lymphatic, or breast cancer.

Back 56

Paraneoplastic syndrome–

Front 57

Causes numerous neurologic symptoms (difficulty in walking or swallowing, loss of muscle tone, loss of fine motor coordination, slurred speech, memory loss, vision problems, sleep disturbances, dementia, seizures, sensory loss in the limbs, and vertigo or dizziness).

Back 57

Paraneoplastic syndrome–

Front 58

Clinical Features of Cancer

Back 58

Pain
Fatigue
Cachexia
Anemia
Leukopenia and Thrombocytopenia
Infection

Front 59

Avoidable causes of cancer:

Back 59

Cigarette smoking
Ionizing radiation
Ultraviolet Radiation (UV) Electromagnetic Fields (EMF)

Front 60

Cigarette smoking is the #1 most important cause of cancer (more than 60 carcinogens have been identified in cigarette smoke).

Back 60

*

Front 61

Smoking accounts for 1 of every 5 deaths in the US.

Back 61

*

Front 62

Three ways to avoid lung cancer:

Back 62

stop smoking
stop smoking
stop smoking

Front 63

the atomic bombs in Hiroshima &
Nagasaki caused acute leukemias (often a 10-30
year latent period), thyroid carcinoma, & breast
carcinoma.

Back 63

Ionizing radiation –

Front 64

We accumulate the DNA damaging effects (both direct
DNA damage & free radical damage) of ionizing
radiation through natural sources (85%) and through
medical imaging (15%). Interventional radiology has the
highest doses of radiation, followed by computed
tomography (CT) and then plain-film radiography.

Back 64

*

Front 65

causes genetic mutation
(DNA damage); increased TNFα (proinflammatory cytokine) in skin.

Back 65

Ultraviolet Radiation (UV) –

Front 66

Basal cell carcinoma (90%)
Squamous cell carcinoma

Back 66

related to cumulative
lifetime UV exposure

Front 67

the first stage of which is
called actinic keratosis

Back 67

Squamous cell carcinoma

Front 68

Melanoma

Back 68

related to episodes of sunburn

Front 69

) - microwave, cell phones,
transformers, appliances, high-voltage transmission lines, etc.

Back 69

Electromagnetic Fields (EMF)

Front 70

Past studies of occupational magnetic field exposure in adults
showed very small increases in leukemia and brain tumors. However,
more recent, well-conducted studies have shown inconsistent
associations with leukemia, brain tumors, and breast cancer.

Back 70

*

Front 71

Types of cells:

Back 71

Ependymal cells
Microglia
Schwann cells
Oligodendroglia
Astrocytes
Neurons

Front 72

- transmit impulses; afferent & efferent

Back 72

Neurons

Front 73

Astrocytes – fill space between neurons & surround blood
vessels in CNS (role in blood-brain barrier)

Back 73

Astrocytes

Front 74

– form myelin sheath in CNS

Back 74

Oligodendroglia

Front 75

– form myelin sheath in PNS

Back 75

Schwann cells

Front 76

– phagocytic cells in CNS (remove debris)

Back 76

Microglia

Front 77

– line ventricles & help elaborate CSF
(part of the blood-CSF barrier)

Back 77

Ependymal cells

Front 78

Nerve Injury and repair

Back 78

Nerve cells are non-dividing cells; injury can cause permanent
loss of function.

Front 79

Etiology:

Back 79

tourniquet use, fractures, MVA, crush, compression,
compartment syndrome, laceration, penetrating trauma,
stretch, diseases, cold, toxins, ischemic reperfusion, etc.

Front 80

- follows different forms of nerve injury (even result of
surgery). They occur at the end of injured nerve fibers as a form of ineffective,
unregulated nerve regeneration; often very painful.

Back 80

Neuroma (traumatic neuroma)

Front 81

occurs in peripheral nerves. It is a
process by which the damaged segment of a nerve is
phagocytosed, beginning at the first intact node of Ranvier.
The Schwann cell tubes also are phagocytosed to prevent
obstruction of the regenerating axon.

Back 81

Wallerian degeneration

Front 82

Regeneration of a peripheral nerve occurs at rate of
approximately 1-3 mm/d. For example, injuries to the midshaft
level of the humerus may have to cross as many as 16 cm
(>5 mo) before innervating the brachioradialis or wrist extensors.

Back 82

*

Front 83

Motor endplates must be reinnervated within 18 months of
trauma for function to be resumed.

Back 83

*

Front 84

Seddon's grading system for nerve injuries:

Back 84

1) Neurapraxia (mildest)
2) Axonotmesis
3) Neurotmesis (most severe)

Front 85

Sunderland (1951) categorized nerve injuries
into 5 grades.

Back 85

*

Front 86

Neurapraxia

Back 86

is a reduction or complete block of
conduction across a segment of a nerve with axonal
continuity conserved (without loss of nerve sheath continuity
and without Wallerian degeneration). Nerve conduction is
preserved both proximal and distal to the lesion but not
across the lesion. A person's foot "falling asleep" after his
legs have been crossed is an example of a functional loss
without abnormal change.

Front 87

Axon recovers without degeneration & regeneration

Back 87

*Neurapraxia

Front 88

Axonotmesis

Back 88

is a result of damage to the axons with
preservation of the neural connective tissue sheath
(endoneurium), epineurium, Schwann cell tubes, and other
supporting structures. Thus, the supporting architecture is
relatively preserved. This can guide proximal axonal
regeneration to reinnervate distal target organs. Distal
Wallerian degeneration occurs in axonotmesis.

Front 89

Axonotmesis

Back 89

Axon does regenerate & reestablish connection

Front 90

Neurotmesis

Back 90

occurs when the axon, myelin, and
connective tissue components are damaged and disrupted or
transected. Distal Wallerian degeneration occurs. Recovery
through axonal regeneration cannot occur. This grade of injury
includes nerve lesions in which external continuity is preserved
but intraneural fibrosis occurs and blocks axonal regeneration.

Front 91

Neurotmesis

Back 91

Axon cannot regenerate & reestablish connection

Front 92

– 8 cranial bones

Back 92

Cranium

Front 93

– 33 bones

Back 93

Vertebral column

Front 94

3 protective membranes: dura mater, arachnoid,
pia mater;
spinal cord is anchored to vertebrae by filum terminale

Back 94

Meninges –

Front 95

CSF - a clear bodily fluid that occupies the subarachnoid space and the ventricular system around and inside the brain and spinal cord. 500 ml made/day. CSF volume is 135 to150 ml. Provides neutral buoyancy for brain.

Back 95

CSF -

Front 96

(Circle of Willis) 4 arteries supply
blood to this “circle”

Back 96

cerebral arterial circle

Front 97

continuous capillaries (endothelial cells have tight junctions & few vesicles) surrounded by a layer of astrocytes, limiting what passes into brain tissue

Back 97

Blood brain barrier (BBB)

Front 98

“unpleasant sensory and emotional experience associated with
actual or potential tissue damage or described in terms of such
damage”, International Assoc. for the Study of Pain and the American Pain Society.

Back 98

pain

Front 99

“whatever the experiencing person says it is, existing
whenever he says it does” according to Margo McCaffery, R.N.
This is probably a better clinically relevant concept of pain.

Back 99

pain

Front 100

Three systems interact in the experience of pain:

Back 100

Sensory discriminative system Motivational/affective system Cognitive/evaluative system

Front 101

– afferent input to CNS about strength, intensity, & temporal and spatial aspects of pain

Back 101

Sensory discriminative system

Front 102

– determines the individual’s conditioned or learned approach/avoidance behaviors

Back 102

Motivational/affective system

Front 103

– interpretation of appropriate pain behavior based on cultural preferences, gender roles, life experiences, etc.

Back 103

Cognitive/evaluative system

Front 104

Theories of Pain:

Back 104

Neuromatrix theory
Gate control theory
Specificity theory

Front 105

– the intensity of the pain is directly related to the
amount of tissue injury. 17th century idea.

Back 105

Specificity theory

Front 106

(1965) - This theory states that pain is a function
of the balance between the information traveling into the spinal cord through
large nerve fibers and information traveling into the spinal cord through small
nerve fibers (large nerve fibers carry non-nociceptive information and small
nerve fibers carry nociceptive information). If the relative amount of activity is
greater in large nerve fibers, there should be little or no pain. However, if
there is more activity in small nerve fibers, then there will be pain.
Implanting electrical stimulating electrodes in patients with
severe pain can relieve pain in some patients.

Back 106

Gate control theory

Front 107

– the brain generates a neural pattern that
produces pain (some chronic pain, phantom limb pain) either on its own or
upon nonpainful sensory input

Back 107

Neuromatrix theory

Front 108

Pain Mechanisms

Back 108

Pain receptors (nociceptors) and chemical mediators play a critical role
The spinal cord is a vital part of pain processing
Ultimately, the brain decides whether a stimulus is painful and what the body needs to do about it.
Pain modulation

Front 109

Relays all sensory input except
olfactory to cerebral cortex

Back 109

Thalamus

Front 110

Neuromodulator release (from neurons) is triggered by tissue
injury (prostaglandins, bradykinin) and chronic inflammation
(lymphokines).

Back 110

*

Front 111

Excitatory neuromodulators – substance P, glutamate,
somatostatin, vasoactive intestinal peptide (VIP), calcitonin-
gene-related peptide

Back 111

Increase nociception

Front 112

Inhibitory neuromodulators – gamma-aminobutyric acid
(GABA), glycine, 5-hydroxytryptamine (serotonin precursor),
norepinephrine, endorphins

Back 112

Decrease nociception

Front 113

- the perception of a painful stimulus.

Back 113

Nociception

Front 114

- a sensory receptor that responds to potentially
damaging stimuli by sending nerve signals to the spinal cord
and brain

Back 114

Nociceptor

Front 115

- a decreased sensitivity to painful stimuli.

Back 115

Hypoalgesia

Front 116

- an increased sensitivity to pain

Back 116

Hyperalgesia

Front 117

- Over time, individuals taking
opioids can develop an increasing sensitivity to noxious stimuli

Back 117

Opioid-induced hyperalgesia

Front 118

- painful response to previously non-noxious stimuli

Back 118

Allodynia

Front 119

Three possibilities involved in stimulation of nociceptors:

Back 119

Direct stimulation of nociceptors or sensitizing them to the effects of nociceptive stimuli
Perpetuating the inflammatory responses that lead to mediator release
Inciting neurogenic reflexes that increase response to nociceptive stimuli

Front 120

– neurotransmitters like glutamate and neuropeptides like substance P play significant role.

Back 120

Mediators in the spinal cord

Front 121

There is no objective clinical measurement of pain.

Back 121

*

Front 122

Clinically a patient may be asked to rate the intensity
of their pain on a scale from 0-10.

Back 122

*

Front 123

There are questionnaires that attempt to assess the
“quality” of pain (McGill Pain Questionnaire) or the
“psychosocial” state of the patient with pain
(Multidimensional Pain Inventory).

Back 123

*

Front 124

- are endogenous opioid peptides that
function as inhibitory neurotransmitters; block pain impulse transmission (natural painkillers) & produce euphoria.

Back 124

Endorphins

Front 125

β-endorphin

enkephalin
dynorphin
endomorphins

Back 125

Over 20 different endorphins in humans;
Made in the pituitary, hypothalamus, spinal cord

Front 126

Endorphins bind to opioid receptors on the afferent (sensory) neurons. Opioid receptors are found in CNS, PNS, & gastrointestinal tract.

Back 126

*

Front 127

Release of endorphins is stimulated by exercise, stress, sex, capsaicin, accupuncture, etc.

Back 127

*

Front 128

produce analgesia and a feeling of well-being

Back 128

Endorphins

Front 129

are believed to cause both pre- and post-synaptic inhibition of type C (slow, burning sensation) and type Aδ pain (cold & pressure) fibers where they synapse in the dorsal horns.

Back 129

Enkephalins

Front 130

modulate pain (cause analgesia, or stimulate pain), & are thought to play a role in appetite, & temperature regulation

Back 130

Dynorphins

Front 131

may regulate sedative and arousal behaviors

Back 131

Endomorphins

Front 132

pain suppression during times of stress

Back 132

Function of the Opiate System

Front 133

an important part of an organism’s response to an emergency is a reduction in the responsiveness to pain

Back 133

effective in defense, predation, dominance and adaptation to environmental challenges

Front 134

Pathological Consequences of pain

Back 134

-Fear and anxiety
-Stress response leading to altered immune function
-Acute pain → chronic pain (persistent)

Front 135

(ACTH cortisol)

Back 135

Stress response leading to altered immune function

Front 136

Acute pain → chronic pain (persistent)

Back 136

Persistent pain may involve both peripheral and central sensitization and an altered brain biochemistry
Fatigue and sleep disturbance
Depression
PTSD

Front 137

Opiate drugs:

Back 137

Oxycodone (Oxycontin) and oxycodone + acetaminaphen = Percocet
-morphine sulphate (MS contin)
-meperidine (Demerol)
-Hydromorphone (Dilaudid)
-fentanyl (Duragesic)
-hydrocodone, and hydrocodone + acetaminophen= Lortab, Vicodin
-Methadone

Front 138

– pain from an identifiable physical cause

Back 138

Somatogenic pain

Front 139

– no physical cause determined

Back 139

Psychogenic pain

Front 140

– pain from skin or near body surface

Back 140

Somatic pain

Front 141

– pain from internal structures (organs, bones); may radiate

Back 141

Visceral pain

Front 142

– pain experienced in an area other than the structure
actually causing the pain

Back 142

Referred pain

Front 143

– sudden onset that mobilizes the person to action

Back 143

Acute pain

Front 144

– pain persisting 3-6 months

Back 144

Chronic pain

Front 145

– chronic pain with hyperalgesia (increased sensitivity
to painful stimuli), allodynia (perception that unpainful stimuli are
painful), and spontaneous pain.

Back 145

Neuropathic pain

Front 146

– damage to nerves (PNS)

Back 146

Peripheral pain

Front 147

– lesion or dysfunction in CNS (brain or spinal cord)

Back 147

Central pain

Front 148

– the lowest intensity at which a stimulus
can be perceived as pain. Probably influenced by
genetics but clearly varies from person to person.

Back 148

Pain threshold

Front 149

– the amount of time and intensity of pain that
a person will endure before initiating overt pain responses.

Back 149

Pain tolerance

Front 150

Treatment options in long-term pain care management:

Back 150

-Physical therapy, exercise, massage, heat, cold, etc.
-Accupuncture, biofeedback, cognitive behavioral therapy, hypnosis
-Chiropracter – “spinal adjustments”

Front 151

Treatment options in long-term pain care management:

Back 151

-NSAIDs (aspirin, ibuprofen, acetaminophen, mobic, celebrex)
-Corticosteroids (methylprednisolone)
-Muscle relaxers
-Anti-depressants
-Neurontin (gabapentin) aGABA analogue used to treat neuropathic pain
-Biological response modifiers – Humira (blocks TNFα)
-Neurostimulation [e.g., brain stimulation, spinal cord stimulation,
transcutaneous electrical nerve stimulation (TENS)]

Front 152

Treatment options in long-term pain care management:

Back 152

-Trigger point injections (lidocaine + corticosteroid)
-opiates (oral meds, transdermal patches, buccal tabelets, lollipops, implanted pumps, injection)
-Surgery
-Nerve ablation using Radiofrequency or laser to thermally destroy the nerve

Front 153

In 2008, the World Health Organization (WHO) estimated that approximately 80 percent of the
world population has either no or insufficient access to treatment for moderate to severe pain

Back 153

*

Front 154

WHO pain ladder:

Back 154

Bottom rung (mild pain): Non opioid +/- adjuvant
Middle rung (moderate pain): Weak opioid +/- non opioid +/- adjuvant
Highest rung (severe pain): Strong opioid +/- non opioid +/- adjuvant

Front 155

e.g. paracetamol (acetaminophen) OR non-steroidal anti-inflammatory
drugs (NSAIDs) such as aspirin, diclofenac, ibuprofen

Back 155

Non opioid:

Front 156

2.: tramadol, codeine, dihydrocodeine

Back 156

Weaker opioid

Front 157

3.: morphine, diamorphine (heroin), fentanyl, buprenorphine, oxycodone,
hydromorphone

Back 157

Strong opioid

Front 158

: antidepressants, anticonvulsants, steroids, muscle relaxants, exercise,
psychological support, temperature therapy, primal therapy, hydrotherapy,
acupuncture

Back 158

Adjuvant

Front 159

Every year tens of millions of people around the world, including around four million
cancer patients and 0.8 million HIV/AIDS patients at the end of their lives suffer from
such pain without treatment..



Back 159

*

Front 160

Primarily regulated by the
hypothalamus which receives sensory input about temperature
from peripheral thermoreceptors in skin and central
thermoreceptors in the hypothalamus, spinal cord, & abdominal
organs.

Back 160

Temperature regulation:

Front 161

If the temp is too low the hypothalamus triggers increased
heat production & conservation.

Back 161

*

Front 162

Fever= (100.4 or higher)

Back 162

*

Front 163

: the febrile
response is a temporary resetting of the
hypothalamic thermostat (by PGE2) to a higher point in
response to pyrogens (endogenous or exogenous)

Back 163

Pathogenesis of Fever (pyrexia)

Front 164

– body overheats without changing its setpoint.

Back 164

Hyperthemia

Front 165

LPS (a lipopolysaccharide found in the
outer membrane of Gram-negative bacteria). [E. coli,
Salmonella, Pseudomonas, Legionella, etc.]

Back 165

Exogenous pyrogen –

Front 166

- all are cytokines (IL-1, IL-6, TNFα)

Back 166

Endogenous pyrogens

Front 167

Is fever beneficial ?

Back 167

some studies suggest that patients recover more rapidly from
infections or critical illness due to fever. Others state, “there is
little evidence that fever facilitates recovery from disease or
assists the immune system in mounting a response”. Thus, the
question remains controversial.

Front 168

Theoretical or actual benefits:

Back 168

Suboptimal bacterial growth- due to temp directly or effect
on mineral (Fe, Zn, Cu) availability
2) Increase lysosomal activity-cells autodestruct
3) Increases PMN motility
4) Enhanced phagocytosis
5) Increased interferon production (antiviral)
6) Increased T cell proliferation
7) Clinical sign of infection or inflammation

Front 169

Brain Injury Mechanisms

Back 169

Hypoxia and ischemia
Excitatory amino acid injuryCa2+ signaling disruption
Increased Intracranial Volume and Pressure

Front 170

Treatment options in long-term pain care management:

Back 170

-NSAIDs (aspirin, ibuprofen, acetaminophen, mobic, celebrex)
-Corticosteroids (methylprednisolone)
-Muscle relaxers
-Anti-depressants
-Neurontin (gabapentin) aGABA analogue used to treat neuropathic pain
-Biological response modifiers – Humira (blocks TNFα)
-Neurostimulation [e.g., brain stimulation, spinal cord stimulation,
transcutaneous electrical nerve stimulation (TENS)]

Front 171

Treatment options in long-term pain care management:

Back 171

-Trigger point injections (lidocaine + corticosteroid)
-opiates (oral meds, transdermal patches, buccal tabelets, lollipops, implanted pumps, injection)
-Surgery
-Nerve ablation using Radiofrequency or laser to thermally destroy the nerve

Front 172

In 2008, the World Health Organization (WHO) estimated that approximately 80 percent of the
world population has either no or insufficient access to treatment for moderate to severe pain

Back 172

*

Front 173

WHO pain ladder:

Back 173

Bottom rung (mild pain): Non opioid +/- adjuvant
Middle rung (moderate pain): Weak opioid +/- non opioid +/- adjuvant
Highest rung (severe pain): Strong opioid +/- non opioid +/- adjuvant

Front 174

e.g. paracetamol (acetaminophen) OR non-steroidal anti-inflammatory
drugs (NSAIDs) such as aspirin, diclofenac, ibuprofen

Back 174

Non opioid:

Front 175

2.: tramadol, codeine, dihydrocodeine

Back 175

Weaker opioid

Front 176

3.: morphine, diamorphine (heroin), fentanyl, buprenorphine, oxycodone,
hydromorphone

Back 176

Strong opioid

Front 177

: antidepressants, anticonvulsants, steroids, muscle relaxants, exercise,
psychological support, temperature therapy, primal therapy, hydrotherapy,
acupuncture

Back 177

Adjuvant

Front 178

Every year tens of millions of people around the world, including around four million
cancer patients and 0.8 million HIV/AIDS patients at the end of their lives suffer from
such pain without treatment..



Back 178

*

Front 179

Primarily regulated by the
hypothalamus which receives sensory input about temperature
from peripheral thermoreceptors in skin and central
thermoreceptors in the hypothalamus, spinal cord, & abdominal
organs.

Back 179

Temperature regulation:

Front 180

If the temp is too low the hypothalamus triggers increased
heat production & conservation.

Back 180

*

Front 181

Fever= (100.4 or higher)

Back 181

*

Front 182

: the febrile
response is a temporary resetting of the
hypothalamic thermostat (by PGE2) to a higher point in
response to pyrogens (endogenous or exogenous)

Back 182

Pathogenesis of Fever (pyrexia)

Front 183

– body overheats without changing its setpoint.

Back 183

Hyperthemia

Front 184

LPS (a lipopolysaccharide found in the
outer membrane of Gram-negative bacteria). [E. coli,
Salmonella, Pseudomonas, Legionella, etc.]

Back 184

Exogenous pyrogen –

Front 185

- all are cytokines (IL-1, IL-6, TNFα)

Back 185

Endogenous pyrogens

Front 186

A child with fever over 102.2 should be treated
A fever of 105 or more in a child is a medical emergency

Back 186

*

Front 187

Is fever beneficial ?

Back 187

some studies suggest that patients recover more rapidly from
infections or critical illness due to fever. Others state, “there is
little evidence that fever facilitates recovery from disease or
assists the immune system in mounting a response”. Thus, the
question remains controversial.

Front 188

Theoretical or actual benefits:

Back 188

Suboptimal bacterial growth- due to temp directly or effect
on mineral (Fe, Zn, Cu) availability
2) Increase lysosomal activity-cells autodestruct
3) Increases PMN motility
4) Enhanced phagocytosis
5) Increased interferon production (antiviral)
6) Increased T cell proliferation
7) Clinical sign of infection or inflammation

Front 189

Brain Injury Mechanisms

Back 189

Hypoxia and ischemia
Excitatory amino acid injuryCa2+ signaling disruption
Increased Intracranial Volume and Pressure

Front 190

If the temp is too low the hypothalamus triggers increased
heat production & conservation.

Back 190

*

Front 191

Fever= (100.4 or higher)

Back 191

*

Front 192

: the febrile
response is a temporary resetting of the
hypothalamic thermostat (by PGE2) to a higher point in
response to pyrogens (endogenous or exogenous)

Back 192

Pathogenesis of Fever (pyrexia)

Front 193

– body overheats without changing its setpoint.

Back 193

Hyperthemia

Front 194

LPS (a lipopolysaccharide found in the
outer membrane of Gram-negative bacteria). [E. coli,
Salmonella, Pseudomonas, Legionella, etc.]

Back 194

Exogenous pyrogen –

Front 195

- all are cytokines (IL-1, IL-6, TNFα)

Back 195

Endogenous pyrogens

Front 196

A child with fever over 102.2 should be treated
A fever of 105 or more in a child is a medical emergency

Back 196

*

Front 197

Is fever beneficial ?

Back 197

some studies suggest that patients recover more rapidly from
infections or critical illness due to fever. Others state, “there is
little evidence that fever facilitates recovery from disease or
assists the immune system in mounting a response”. Thus, the
question remains controversial.

Front 198

Theoretical or actual benefits:

Back 198

Suboptimal bacterial growth- due to temp directly or effect
on mineral (Fe, Zn, Cu) availability
2) Increase lysosomal activity-cells autodestruct
3) Increases PMN motility
4) Enhanced phagocytosis
5) Increased interferon production (antiviral)
6) Increased T cell proliferation
7) Clinical sign of infection or inflammation

Front 199

Brain Injury Mechanisms

Back 199

Hypoxia and ischemia
Excitatory amino acid injuryCa2+ signaling disruption
Increased Intracranial Volume and Pressure

Front 200

Traumatic Brain Injury (TBI)

Back 200

Coup-contrecoup injury
Concussion the most common type TBI

Front 201

Cerebral edema

Back 201

Vasogenic-↑ in ECF
Cytotoxic-↑ in cell volume

Front 202

Cerebrovascular Injury (stroke)
Traumatic Brain Injury (TBI)

Back 202

Brain Injury

Front 203

Second-impact syndrome (SIS)

Back 203

SIS is a condition in which the brain swells rapidly and catastrophically after a person suffers a second concussion before symptoms from an earlier one have subsided. This deadly second blow may occur days, weeks or minutes after an initial concussion, and even the mildest grade of concussion can lead to SIS. The condition is often fatal, and almost everyone who is not killed is severely disabled. The cause of SIS is uncertain, but it is thought that the brain's arterioles lose their ability to regulate their diameter, and therefore lose control over cerebral blood flow, causing massive cerebral edema.

Front 204

Cerebrovascular accidents (Stroke)

Back 204

3rd leading cause of death and disability

Front 205

causes neurologic dysfunction lasting < 24 hrs. a “mini stroke”.

Back 205

Transient Ischemic Attack (TIA)

Front 206

Ischemic stroke (atherosclerosis)

Back 206

Thrombus- blood clot
Embolus- detached, itinerant intravascular mass (plaque, tumor cells, mycelia, etc)

Front 207

(hypertension, aneurysm, amyloid protein buildup, AV malformation, cancer, anti-clotting meds)

Back 207

Hemorrhagic stroke

Front 208

Manifestations of Brain Injury

Back 208

Global (level of consciousness) vs. Local (motor and sensory function)
Cerebral hemispheres are the most susceptible to damage (concurrent cerebral hemisphere injury or reticular activating system injury) → alterations in consciousness range from confusion to coma
Pupillary reflexes and eye movements
Decorticate and decerebrate posturing (used in grading coma)
Respiratory responses
Persistent Vegetative State-loss of all cognition and awareness of self and surroundings (?). Reflex and vegetative functions remain.

Front 209

- irreversible loss of all functions including brainstem

Back 209

Brain Death

Front 210

- rigidity, flexion of the arms, clenched fists, and extended legs
(held out straight). The arms are bent inward toward the body with the wrists and fingers
bent and held on the chest. Indicates damage to the corticospinal tract, the pathway
between the brain and spinal cord..

Back 210

Decorticate posturing

Front 211

- arms and legs being held straight out, the toes being pointed
downward, and the head and neck being arched backwards. The muscles are tightened
and held rigidly. Indicates a severe injury to the brain at the level of the brainstem

Back 211

Decerebrate posturing

Front 212

Glasgow Coma Scale


Back 212

The scale comprises three tests: eye, verbal and motor responses. The three values separately as well as their
sum are considered. The lowest possible GCS (the sum) is 3 (deep coma or death), while the highest is 15
(fully awake person).

Front 213

Neurodegenerative Disorders

Back 213

Alzheimer Disease
Parkinson Disease
Huntington disease
Multiple Sclerosis
Down syndrome

Front 214

Alzheimer Disease (AD)

Back 214

is a progressive brain disorder that affects areas of the brain involved in memory, intelligence, judgment, language, and behavior affecting 5.3 million Americans. One in 8 people over the age of 65 is affected by AD. It is the most common form of mental decline or dementia in older adults.

Front 215

Alzheimer Disease (AD)

Back 215

Degenerative, progressive disease that causes specific defects in neurons resulting in impaired memory, thinking, and behavior

Front 216

Alzheimer Disease (AD)

Back 216

Cause is unknown; suspected causes include aluminum, viruses, prion.

Front 217

Alzheimer Disease (AD)

Back 217

APOE-4 is a risk factor for AD (APOE-4 is a variant of APOE that occurs in 15% of the population); smoking is a known risk factor

Front 218

Alzheimer Disease (AD)

Back 218

Treatment: memory aids, drugs (Aricept, Namenda, alone or together) are minimally helpful

Front 219

Drugs for AD treatment

Back 219

-Aricept is an acetylcholinesterase inhibitor

-Namenda block abnormal glutamatergic activity (glutamate is a neurotransmitter)

Front 220

Pathogenesis of AD

Back 220

Morphological changes

Biochemical changes

Cellular changes

Front 221

Morphological changes involve two characteristic lesions (observed at autopsy):

Back 221

Neurofibrillary tangle –neurons contain abnormal intracellular structure consisting of “tau” protein
Senile plaque –extracellular accumulations of amyloid-β in the grey matter of the brain; amyloid is toxic to neurons

Front 222

involve a decrease in acetylcholine; and abnormal fragmentation of amyloid precursor protein (APP)

Back 222

Biochemical changes

Front 223

involve a loss of neurons & synapses

Back 223

Cellular changes

Front 224

Progression of AD Early stages

Back 224

patient remains fairly independent
Diminished problem solving capacity, ability to cope with complex situations and think abstractly
Emotional lability
Forgetfulness
Apathy
Loss of recent memory

Front 225

As the disease progresses, the patients behavior becomes more erratic and bizarre, with a tendency toward confusion, wandering and violent outbursts

Back 225

Progression of AD

Front 226

Later stages involve incontinence and the loss of the ability to care for basic personal needs or recognize family members

Back 226

Progression of AD

Front 227

Death is usually the result of malnutrition or infection

Back 227

Progression of AD

Front 228

Parkinson disease

Back 228

Degenerative disorder of the neurons of the basal ganglia and nigro-striatal pathway.  These neurons produce dopamine, which is the chemical messenger that allows the body's muscles and motor system to function normally.  The loss of dopamine neurons results in the inability to control movements properly.

Front 229

Parkinson disease

Back 229

Syndrome characterized by rhythmic tremors (resting tremors), bradykinesia (decrease in mvt), muscle rigidity, and a loss of postural reflexes, dysphagia, gait disturbances, drooling, constipation, depression, dementia.

Front 230

Parkinson disease

Back 230

Symptoms result from a depletion of dopaminergic activity (inhibitory) and a relative excess of cholinergic (excitatory) activity in the caudate & putamen (nuclei in basal ganglia)

Front 231

Abnormal aggregate of the
protein α-synuclein

Back 231

Lewy Body

Front 232

The four primary symptoms of PD are:

Back 232

tremor, or trembling in hands, arms, legs, jaw, and face;
rigidity, or stiffness of the limbs and trunk;
bradykinesia, or slowness of movement;
postural instability, or impaired balance and coordination.

Front 233

Treatment of PD (not cure):

Back 233

patients are given levodopa combined with carbidopa. Carbidopa delays the conversion of levodopa into dopamine until it reaches the brain.  Nerve cells can use levodopa to make dopamine and replenish the brain's dwindling supply.
Anticholinergics may help control tremor and rigidity
An antiviral drug, amantadine, also appears to reduce symptoms

Front 234

Parkinson disease

Back 234

patients may experience only minor motor problems or may become severely disabled