What age is more likely to experience ADR?
Older than 75
What sex is more likely to experience ADR?
Female
What ethnicity is more likely to experience ADR?
White
Risk factors of ADR
� Concomitant alcohol abuse
� New drugs
� Number of drugs
� Dosages
� Concomitant herbal compounds
� Duration of treatment
� Noncompliance
� Small stature
Presence of underlying conditions (Renal insufficiency)
Common signs of Drug Toxicity
o Rashes
o Fever
o Jaundice
Adverse Skin Reactions that occur with ADR
o Erythema
o Discoloration
o Itching
o Burning
o Urticaria (hives)
o Eczema
o Acne
o Alopecia
o Bulla
o Purpura
Non skin related S&S for ADR
� Altered Taste
� Anxiety
� Dizziness
� HA
� Nasal Congestion
� Shakiness
� Vomiting
� Cramps
� Dyspnea
� Hypo/hypertension
� Palpitations
� Tachycardia
� Persistent Vomiting
� Seizures
� Pulmonary Edema
� Arrhythmia
S&S for large vasculitis
limb claudication, aortic dilation, & bruits (vascular murmur)
S&S for medium vasculitis
cutaneous nodules, gangrene of the digits, mononeuritis multiplex, & Microaneurysms
S&S for small vasculitis
purpura, glomerulonephritis, & alveolar hemorrhage
Common S&S for all sizes of vasculitis
� Fever
� Arthralgias
� Arthritis
� Weight loss
� Malaise
discoid lupus erythematosus
chronic disorder, primarily of the skin, characterized by lesions that are covered with scales
Acute Inflammation S&S
o Fever ( > 100 deg)
o Tachycardia ( > 100 BPM at rest)
o Increased Hypermetabolic State
o Elevated serum protein levels, Elevated WBCs
Chronic Inflammation S&S
� Lymphocytes
� Plasma Cells
� Macrophages
� Fibrosis
Systemic effects of chronic inflammation
� Anemia
� Fatigue
� Leukocytosis
� Lymphocytosis
Increased intravascular fluid does what to pulse rate/respiratory rate/blood pressure?
Increased Pulse and Respiration
Decreased intravascular fluid does what to pulse rate/respiratory rate/blood pressure?
Decreased BP and Increased PR and Respirations
NSAID side effects
GI discomforts, GI ulceration, renal impairment, photosensitivity
s/s of rheumatoid arthritis
� Morning stiffness
� Anorexia
� Weight loss
� Fatigue/Malaise
� Joint involvement
� Immobility & inflammation
� Muscle atrophy
� Subcutaneous nodules
Systemic Lupus Erythematosus causes
*Unknown etiology
*Environmental Triggers
*Viruses, UV light, certain medications, estrogen
Systemic Lupus Erythematosus most serious complications
affect the heart, kidneys, & CNS
What sex is affected by SLE more often?
Female, 8 times more likely, increases to 15 times during child-bearing years
Signs of SLE
Butterfly Rash, and Rheumatoid Nodules
Systemic factors that influence healing
� General nutritional status
� Vitamin C & Proteins
� Psychological well-being
� Presence of CV disease
� Cancer
� Hematologic Disorders
� Systemic Infections
� Diabetes Mellitus
� Corticosteroid or immunosuppressive therapy
Purpura
Pitting edema scale 1+
Barely Perceptible Depression [2mm]
Pitting edema scale 2+
Skin rebounds to its original contour in <10 secs, [4mm]
Pitting edema scale 3+
Skin rebounds within 10-15 seconds [6mm]
Pitting edema scale 4+
Takes >20 seconds to rebound [8mm]
Increased extravascular fluid results
Edema, Ascites, or Pleural Effusion
Decreased extravascular fluid results
Decreased Skin Turgor and Fatigue (will remain elevated and look like a "tent")
How much of body fluid is intracellular?
2/3
How much of body fluid is extracellular?
1/3
Ligament/tendon healing: Acute/Max Protection phase
o Hemorrhagic (Day 1)
� Blood clot between ruptured tissues
o Inflammatory (Day 1-10)
� Chemical, cellular, vascular responses
Ligament/tendon healing: Sub-Acute/Mod Protection phase
� Fibroblasts > Collagen & Matrix Proteins
� Capillary Buds (Neovascularization)
� Wound Closure in 3-6 weeks
Ligament/tendon healing: Chronic/Min Protection phase
o Remodeling & Maturation (6 weeks - 3 years)
� Connective tissue characteristics change
� Decrease in number and types of cells
� Matrix density increases
� Matrix fiber orientation more longitudinal
� Maturation Cont.'s for many months
% of tensile strength regained 6 months after injury
50%
% of tensile strength regained 1 year after injury
80%
% of tensile strength regained 1-3 year after injury
100%
Disuse atrophy
when prolonged inactivity results in the muscles getting smaller in size
Articular cartilage healing prognosis
� Generally, lacks the blood supply to repair
� Chance of repair if injured involves the sub-chondral bone (50%)
� Most commonly leads to degeneration
SINSS
Dude c'mon you should know this by now
Key element of bone healing
o Blood supply
o Micromovement may FACILITATE clinical union
o Macromovement may INHIBIT and prevent clinical union
How do you treat an overuse injury with chronic inflammation at first?
As an acute
Types of Hypertension
1. Borderline
2. Sustained
a. occurs over 3 testing periods
3. Labile
a. comes & goes
4. Malignant
a. markedly elevated BP
Usually not responsive to typical medications
Stages of hypertension
Elevated=120-129/<80
Stage 1= 130-139/80-89
Stage 2= >140/>90
Hypertensive crisis= >180/>120
Arteriosclerosis
the thickening and hardening of the walls of the arteries, due to hypertension
S&S of atherosclerosis
� Arterial wall damage
� Permits the infiltration of macromolecules
� Platelets aggregate at the site of injury and plug up the wound
� Cholesterol-filled plaques can take years to form
orthostatic hypotension causes
o Prolonged Immobilization
o Anti HTN meds
o Peripheral neuropathy
o SCI
o Volume depletion (burns, DM, Na or K depletion)
o Venous pooling
o Performing the Valsalva maneuver
o Autonomic system dysregulation
orthostatic hypotension signs
Drop in systolic pressure of >20 mm Hg and/or pulse increase of 20 bpm
orthostatic hypotension symptoms
Light-headedness, dizziness, nausea, loss of consciousness and sudden weakness.
S&S of Buerger's disease
� Episodic & Segmental
� Intermittent claudication
o localized to arch of foot or palm of hand
� Raynaud's phenomenon
� Coldness, numbness, tingling or burning of the affected hand or foot
S&S of venous insufficiency
� Wet & weepy wounds
� Purplish color is due to hemosiderin/fibrin deposits in the "gaiter" region
Atherosclerosis
Blockage of the LUMEN of the arteries
Arteriolorsclerosis
Thickening of the arterioles
Monckeberg's Medial Sclerosis
Tunica media of vessels becomes CALCIFIED
Berry or Sacular Aneurysm
a. 35% mortality rate
b. Located in cerebral area typically
c. Due to congenital defects
d. Rupture leads to subarachnoid hemorrhage
fusiform aneurysm
a spindle-shaped bulge, Lumen has increased in size due to atherosclerosis
dissecting aneurysm
A condition in which the inner layers of an artery, such as the aorta, become separated, allowing blood (at high pressures) to flow between the layers.
false aneurysm
rupture of the arterial walls, causing pouching
What patient population is more at risk for Monckeberg's medial sclerosis?
This usually occurs in patients with diabetes mellitus due to the excess glycosylation of proteins
Pathogenesis of primary/secondary hypertension
vessels thicken > arteriolorsclerosis > leading to L ventricular enlargement
S&S of arterial insufficiency
� Intermittent claudication
� Reduced or absent pulses distal to obstruction
� Burning ischemic pain at rest
� Ischemic extremities are characterized by decreased skin temperature, dry, scaly or shiny skin, poor nail & hair growth, & ulcerations on WBing
Risk factors of peripheral vascular disease
� Age
� Smoking
� Diabetes
� HTN
� Hyperlipidema
� Ethnicity: African American
Commonalities in S&S of all venous disorders
� Swelling
� Warmth & blue discoloration of extremity
� Dependent edema
� Prominence of superficial veins
� Skin ulcerations & tenderness
� Deep calf tenderness
� Fever
� Chills
� Malaise
� Cyanosis of affected extremity
Special test for DVT
Wells DVT score
S&S of thoracic outlet syndrome
� Paraesthesias of fingers
� + Adson's sign
� + result from hyperabduction
� + result from costoclavicular test
� Pain in anterior chest wall
Adson's sign
obliteration of the radial pulse when the arm is abducted to a position above the shoulder, causing compression of the proximal vessel; associated with thoracic outlet syndrome
S&S of ankylosing spondylitis: Early stages
o Low grade fever
o Fatigue
o Anorexia, wt. loss
o Anemia
o Sacroilitis
o Spasm of paravertebral muscles
o Intermittent LBP
S&S of ankylosing spondylitis: Advanced stages
o Constant LBP
o Ankylosis
o Muscle wasting in shoulder & pelvis
o Loss of lumbar lordosis
o Marked kyphosis
o Decreased chest expansion
o Arthritis
o Iritis (inflammation of the iris)
o Carditis
o Pericarditis
o Fatigue & weight loss
o Low grade fever
Antibody production
B lymphocytes are antibody factories
IgM
o Largest immunoglobulin that predominated in initial immune response
� Mostly in intravascular compartment
IgA
Defends external body surfaces, mucus membrane
IgD
Serves mainly as an antigen receptor & may function in controlling lymphocyte activation or suppression
IgG
The major antibacterial & antiviral antibody & is the predominant antibody in the blood
IgE
o Primary for parasitic infections
� Also functions by activating mast cells & releasing histamine in allergic reactions, anaphylaxis, asthma & urticaria
Type 1 hypersensitivity
IgE mediated hypersensitivity
Allergies, Anaphylaxis, Atopy
Type 2 hypersensitivity
IgM or IgG formed against SELF, specifically on SURFACE of own body
Type 3 hypersensitivity
o Immune complex diseases
o Forms antibodies on something floating IN the body, NOT on surface
Type IV hypersensitivity delayed
� antigen processed in macrophage > antigen recognition > T cell activation
� Amplification & recruitment of macrophages & T cells
� Damage to area where antigen is present
Type IV hypersensitivity cell mediated cytotoxicity
� Target antigen after recognition of antigen by T cells > activation of T helper & killer cells
Destruction of target cells & adjacent tissues
Autograft
graft from a person's own body
Xenograft
a graft from another species
Isograft
use of identical twin's tissue
Allograft
skin graft from another person or a cadaver
Mononuclear cells
monocytes and lymphocytes
Granulocytes
neutrophils, eosinophils, basophils
Natural killer cells and immunity
� Larger granular lymphocytes
� Function is to KILL viruses, other intracellular microbe-infected cells, & tumor cells
� Kill without prior sensitization or activation
How do neutrophils kill?
- Kills via phagocytosis, digestion, and
respiratory burst
- When a bacteria is detected, neutrophils
degranulate
(discharge their lysosome enzymes into the tissue fluid), which catalyze a reaction called the
respiratory burst
S&S of anaphylaxis: General
Malaise and weakness
S&S of anaphylaxis: Dermal
Hives, erythema
S&S of anaphylaxis: Mucosal
Periorbital edema, Nasal congestion, pruiritus, Flushing, pallor, or cyanosis
S&S of anaphylaxis: Respiratory
Sneezing, rhinorrhea, dyspnea
S&S of anaphylaxis: Upper airway
Hoarseness, stridor, tongue & pharyngeal edema
S&S of anaphylaxis: Lower airway
dyspnea, asthma
S&S of anaphylaxis: GI
Increased peristalsis, vomiting, dysphagia, nausea
S&S of anaphylaxis: CV
tachycardia, dysrhythmia, Hypotension, cardiac arrest
S&S of anaphylaxis: CNS
Anxiety, Seizures
Epitopes
Subunits of an antigen that elicit an immune response
Hemocytoblasts
� stem cell from bone marrow that produces blood cells.
� When a hemocytoblast divides into two daughter cells, one of the new cells becomes a blood cell. The other remains a hemocytoblast, ensuring there are always enough hemocytoblasts available.
Interleukin fxn
� Increase the temperature set point in the hypothalamus
� Increase serotonin in brainstem & duodenum
� Stimulate production of prostaglandins thus leading to decreased pain threshold
� Increase syntheses of collagenases resulting in destruction of cartil
passive acquired immunity
Antibodies or sensitized lymphocytes produced by 1 person are transferred to another person
active acquired immunity
Protection by natural or artificial (vaccine) introduction of an antigen into a responsive host
S&S of shingles
� vesicular eruption occurs unilaterally in distribution of a dermatome supplied by the dorsal root or extramedullary cutaneous nerve sensory ganglion
� Usually seen on the trunk or along 5th cranial nerve
� Starts with pain, tingling along the affected s
Causative factors for pressure ulcers
� Unrelieved pressure & results in damage to underlying tissue
o Bony Prominences
o External pressure
o Friction
o Shearing forces
o Maceration
o Decreased skin resilience
o Malnutrition
o Decreased circulation
S&S of cellulitis
� Erythema
� Edema
� Tender
� sometimes nodular
� Erysipelas
Keratinocytes
epithelial cells found in all layers of the epidermis that produces keratin, a skin protein
Melanocytes
a. forms melanin & found in the basal layer
b. Protects against sunburn, UV carcinogenesis, & determines skin color
Langerhans cells
tissue macrophages that aid in immune response
Developing pressure ulcers
Pressure > ischemia > tissue necrosis
layers of epidermis
stratum basale, stratum spinosum, stratum granulosum, stratum lucidum, stratum corneum
S&S of stasis dermatitis
� Itching
� feeling of heaviness
� hemosiderin staining
� open shallow lesions
S&S of contact dermatitis
� Pruritus, erythema, edema occurs 1-2 days after exposure
� Signs begin at site of exposure then extend distally
� May progress to vesiculation, oozing, crusting, & scaling
Primary skin lesion
initial reaction to pathologically altered tissue and may be flat or elevated
ex: macule, papule, plaque, nodule, tumor, wheal, vesicle, pustule
secondary skin lesions
changes that take place in the primary lesion due to infection, scratching, trauma, or various stages of a disease
Ex: scale, crust, thickening, erosion, ulcer, scar, excoriation, fissure, atrophy
In situ
Describing a tumor that has not yet broken through the basement membrane
Stage 0 cancer
carcinoma in situ
Stage 1 cancer
confined to organ of origin
Stage 2 cancer
increased risk of spread because of tumor size
Stage 3 cancer
local CA has spread but may not be disseminated to distant regions
Stage 4 cancer
CA has spread & disseminated to distant sites
Encapsulated neoplasms
� Encapsulation is when a neoplasm grows within a connective tissue or capsule
� Most encapsulated neoplasms are benign
benign neoplasia characteristics
o No Metastasis
o Encapsulated
o Non-invasive
o Slow Growing
o Well Differentiated
o Little or no anaplasa
Malignant neoplasia characteristics
o Metastasis
o Non-encapsulated
o Invasive
o Rapid Growth
o Poorly differentiated
o Anaplasia to varying degrees
When benign & malignant tumors are classified by cell types, they are named by the_____________
tissue of origin
5 major classifications of tumors by cell type?
o epithelial
o connective & muscle
o nerve
o lymphoid
o hematopoietic
Axonotmesis (Class 2)
o Complete interruption of axon with loss of all function subserved by the cell
� Recovery of function may occur if Wallerian degeneration and regeneration occur
Neurometsis (class 3)
o Complete interruption of entire nerve fiber including cell membrane and myelin sheath
� Requires surgical re-attachment if recovery of function is to occur
S&S of carpal tunnel syndrome
� Nocturnal Pain, Tingling, Numbness, Paresthesia
� Muscular Weakness occurs later
� Loss of grip strength, inability to pinch & sensory loss causes clumsiness of the hands
Transient neuropraxia
Due to ischemic block of neuronal conductivity and presents as a rapidly reversible loss of function (arm falling asleep)
Delayed reversible neuropraxia
� due to demyelination and presents as loss of function that recovers after a few weeks following re-myelinization (Bell's palsy, Guillian-Barre)
Myelin production in PNS
Schwann cells
Myelin production in CNS
oligodendrocytes
In a myopathy, weakness tends to be_________
proximal
In a neuropathy, motor symptoms tend to first occur_________
distally
Mononeuropathy
single peripheral nerve is affected
Polyneuropathy
several peripheral nerves affected
Radiculoneuropathy
involves nerve root as it emerges from spinal cord
Polyradiculitis
involvement of several nerve roots > may be from infection causing inflammation
Myopathy
involvement of muscle. Usually involves proximal muscle weakness, wasting, and hypotonia without sensory impairments
Compressive positions of the wrist in CTS
� Sleep
� Computer desk position
� Flexion or Extension = produces ischemia and impingement on the nerve
Guillain-barre syndrome S&S
� 1st symptom is often paraesthesia in the toes, within hours or days distal weakness in the LEs
� Weakness spreads to UEs, trunk, & facial muscles.
� Absence of DTRs
� Palatal & facial muscles involved in � of cases
� If ANS involvement: tachycardia, abn
Myesthenia gravis S&S
� Ptosis (ocular) & diploplia
� Repetition of muscle activity = fatigue
� Proximal muscle weakness variability
� Chewing meat produces fatigue
� Speech is nasal
� Difficulty swallowing (aspiration possible)
collateral sprouting
New axon and dendrite extensions allow existing neurons to form new connections
Neuroplasticity
New connections are made between active neurons to create alternate neural pathways
What nerves are effected by bell's palsy?
Facial Nerve VII
S/S of Bell's Palsy
� Can come on rapidly, often overnight
o Mouth Droops
o Nasolabial Fold flattens
o Palpebral fissure is widened because eyelid doesn't close
� Taste, Lacrimation & Salivation affected
Wallerian degeneration
degeneration of a nerve distal to an injury
Ulnar palsy presentation
� Claw-hand deformity with MCP extension & IP flexion of ulnar distribution
� Flattened hypothenar eminence along with abduction of little finger coincides with weakness of palmaris brevis & abductor minimi
� Atrophy of interossei on dorsal hand
� Paralys
Radial palsy presentation
o If axilla, then weakness in Triceps, Brachioradialis, Supinator
o If damage at upper arm, then triceps is spared
o In both instances, there is paralysis of the wrist extensors, extensors of the thumb, fingers and diminished grip strength
o Sensory loss