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Patho Exam 2 (5-8)

Terms in this set (361)

Role of Chaperones
- Folding of naïve protein
- Refolding of abnormally folded proteins
Role of Proteosomes
- Senescent or abnormal proteins are ubiquinylated
- Ubiquitin guides protein to proteosome where it is degraded into pieces for recycling
Cell Differentiation- what causes it?
- The matrix
- Some genes permanently turned off
- Epigenetic proteins that are binding on DNA and determine what can be transcribed
How many pairs of autosomes
23
- less than 2% code for something
Crossing over
- mixing of parental chromosomes
- random independent event
Short arm of chromosome
p
Long arm of chromosome
q
Primary hemostasis
- Immediate vasoconstriction
- Platelet plug formation- they stick to each other
Secondary hemostasis
- Coagulation cascade fibrin clot
- Clot retraction- more stable and less likely to fall off
Fibrinolysis
- breaking down the clot, still happens as primary
- Plasminogen (inactivated enzyme) plasmin (activated)
- fibrin split products/fibrin degradation products
Fibrinogen
- helps platelets stick together
- this is a positive feed back loop
Intrinsic pathway test
- time to activate clotting pathway Looks better for effect of heprin
Extrinsic Pathway test, what does it look at and what is normal?
- Pro time, INR - 1 is normal 2= 2x as long to get normal clot looks better at warfarin and Coumadin
Platelets, where is it produced and what is it involved in?
- primary and secondary hemostasis
- produced in the bone marrow
percent of platelets in circulatory
- 70%
Percent of platelets in spleen
- 30%
Antiplatelet drugs that affect function
- ASA, warfarin, heparin
- clopidogrel
- eptifibatide
Thrombocytopenia, and numbers
- platelet disorders
- quantitive, platelet count lower than normal
- <100,000/mm3
Platelet dysfunction effects, leads to
- bleeding time
- disorders
Clotting factor disorders
- intrinsic and extrinsic pathway
Normal range of platelets
- 150,000- 350,000
Reasons for thrombocytopenia
- Decreased production
- Altered distribution
- Increased destruction
Bleeding time, what is normal,
- global function of hemostasis - normal is 10 min
If bleeding time increased, and a PTT and INR and platelet count are normal then what is happening?
- a qualitative platelet dysfunction
What can cause decreased production of WBC
- Drugs- chemo
- Radiation
- Bone cancer or metastasis
- Aplastic anemia
Aplastic anemia
- autoimmune, bone marrow stops producing
Decreased lifespan of cells can be due to
- Drugs
- Mechanical prosthetic heart valves
- Infections
- Idiopathic
Relative reasons for low WBC
- Too much fluid, dilution
Reasons for extrinsic elevated
- Vitamin K deficiency
- Liver disease
- DIC- cancer, sepsis
- coumadin (Warfarin)
how to test extrinsic pathway
- PT/ INR
How to test intrinsic pathway
- aPTT
Clotting factor disorders: Intrinsic pathway
- Hemophilia
- A: Factor VIII
- B: Factor IX
- Advanced liver disease
- DIC- Immune system is becoming defective, clots where they shouldn't be
Prothrombin Time/International Normalized Ratio
- Assesses extrinsic pathway of coagulation cascade and efficacy of coumadin
Prothrombin Time/International Normalized Ratio values (low level, mid level, high level and what they are used for)
Prophylaxis - 1.5
Therapeutic - 2-3
Prosthetic heart valves - 2.5-3.5
Erythropoises process
Bone marrow stem cell (Erythropoietin) --> Erythroblasts --> Reticulocytes (Immature red blood cells) --> Erythrocytes (mature red blood cells)
Recipe for RBC Erythropoiesis
- Dietary Iron
- Folate
- Vitamin B12
- Intrinsic factor needed to absorb B12
- Functional kidneys (erythropoietin)
- Functional bone marrow stem cells
RBC labs
- Hematocrit
- Hemoglobin
Ratio of hematocrit and hemoglobin
3:1
Most important assess for anemia
Mean corpuscular volume (MCV) most imprortant because some are related to cell size
RDW
- range of red cell sizes
MCHC
- mean corpuscular hgb concentration- color
- for iron
smear
for shape
Reticulocyte count
- if they're making cells, bone marrow indicator
Total iron binding capacity if elevated, what does that mean?
- Deficient
Normal RBC values for men and women
- Men: 4.7-6.1 million/mm3
- Women: 4.2-5.4 million/mm3
Polycythemia
- elevated RBC
Anemia
- decreased RBC
Hematocrit (HCT), normal for men and women
- % of BV that is RBC
- m - 45
- women - 42%
What can change RBC concentration (HCT)
- age
- actual changes in number or changes in plasma volume (hemodilution or hemoconcentration)
Hemoglobin test, normal values
- oxygen carrying capacity (less if they have anemia)
- M- 14-18g/dl
- W- 12-16 g/dl
HGB numbers will change with what
- RBC count and heamtocrit
Oxygen content =
Dissolved + bound
Dissolved oxygen
- PaO2 x .003
Oxygen bound to HB
- Hb (g/dl) x 1.34 x Sat
What to to worry about with Polycythemia
- Over clotting
Elevated RBC count leads to
- increased viscosity
Primary polycythemia
- Polycythemia vera: malignant proliferation
Secondary Polycythemia
- compensation for chronic hypoxemia or increased altitude (lung disease, kidney thinks its not getting enough o2 and tell bone marrow to make more cells)
Anemia, Iron common causes
- Bleeding, not getting enough in because of GI, losing it more rapidly than getting it, not able to replace them
Iron Anemia
- decreased RBC cound
Absolute Anemia, Iron
- increased loss
- decreased production
Relative Anemia, Iron
- Increased plasma volume
Clinical manifestations of anemia
- Fatigue
- Decreased activity tolerance
- Exertional dyspnea
- Increased respiratory rate (tachypnea)
- Increased heart rate (tachycardia)
- Pallor (Pale)
REasons for anemia
- increased RBC loss or destruction
Reasons for anemia- increased RBC loss or destruction
- Acute blood loss- surgery
- Chronic blood loss
- Destruction/Hemolysis (Genetic, Immune, Mechanical)
Reasons for anemia- Impaired RBC production
- Aplastic anemia - bone marrow isn't working, drugs (chemo)
- Iron, Vitamin B12 or Folate deficiency
- Erythropoietin insufficient (usually when kidneys not working correctly)
Lab diagnosis of anemia
- Low RBC count
- MCHC (size) or MCV (color)
microcytic anemia
-thalocemia missing hemoglobin gene, iorn deficiency
macrocytic anemia causes
- Folate deficiency, or B12
MCHC findings
- Hypochromic - pale is iron deficient
Clues as to what cause anemia: acute blood loss
- hemorrhage): s/s hypovolemia/fluid volume deficit & possible hypovolemic shock; increased reticulocytes
Clues as to what cause anemia: Aplastic, indications
- pancytopenia; infection & bleeding tendencies, decreased reticulocytes
Clues as to what cause anemia: Hemolytic
- increased bilirubin; jaundice, increased reticulocytes, abnormal cells, schistocytes (they're breaking up)
Clues as to what cause anemia: B12 and folate, S/S
- CNS manifestations, pancytopenia
Treatment of anemia: decreased production (Nutritional , aplastic, decreased erythripoietin) HOW TO TREAT
- Nutritional: Supplement iron, B12 or folate
- Aplastic: Treat cause (if possible)
- Decreased erythropoietin: epoetin (Epogen)
Treatment of anemia: Increased loss (acute bleeding, chronic bleeding, hemolytic)
- Acute bleeding: Stop bleeding, transfuse, iron
- Chronic bleeding: Iron, identify bleeding source
- Hemolytic anemia: Specific to disease
Ertythropoeitin therapy
- parenteral
- 1-3 x weekly
- iron supplement for hematopoiesis
Excessive use of Erythropoeitin therapy can lead to
- Myocardial infarction risk
- stroke risk - increased viscosity
HIV SLIDES
...
What makes HIV special?
- Reverse transcriptase differentiates HIV special, and it makes a lot of mistakes so it mutates at a high rate
What does HIV infect?
- CD4 cells, GP 120 of virus, macrophages
Enzymes in HIV
- Reverse transcriptase
- Protease
- Integrase
When screening for HIV what to look for
- Antibodies against HIV proteins
What kind of medications are people with HIV on
- Reverse transcriptase inhibitors and protease
Stage 1 of HIV
- fever, malaise, systemic inflammation, acute viremia (viral replication), highly infectious
Stage 2 of HIV
- Clinical Latency: Few
- Symptoms, but VIRAL Production Continues
Stage 3 of HIV
- Immuno-deficient AIDS
- More infected cells= less easy to treat, treat early
- Opportunistic infections begin(ex: Herpes going down esophagus CD4 dropping below 200 = AIDS)
AIDS Diagnosis
- CD4 counts < 200/µL or
- AIDS indicator condition present
Common HIV manifestations and opportunistic infection
- Wasting syndrome
- Pneumocytosis carinii
- Herpes simplex
- Kaposi's sarcoma
- CMV retinitis
HIV encepthalopathy
- progressive cognitive impairment
- confusion, memory loss, ataxia, inability to perform basic/complex tasks, weakness, impaired speech, incontinence, loss of vision, seizures
- Progressing to global dementia - personality changes, depression, withdrawal, loss of self
HIV diagnostic testing
- ELISA
- Antigen testing
- Genotype and Viral load testing
How to monitor HIV progression
- Plasma viral load
- CD4 count
Slowing the antiretroviral resistance
- Compliance
- Combination drugs
- Genotype and resistance testing
5 classes of Antiretroviral therapy
- Reverse transcriptase inhibitors
- Protease inhibitors
- CCR5 co receptor antagonist
- Fusion inhibitors
- Integrase inhibitors
CANCER
...
- oma
- benign tumor
- carcinoma or - sarcoma
- malignant tumor
Exceptions of naming systems
- lymphoma, neuroblastoma, & melanoma are all malignant
Benign tumor
o Slow growth
o Local; often encapsulated
o Histologically well differentiated
o Function similarly to normal cells
o Rarely recur
Malignant tumor
o Rapid growth
o Metastasis risk
o Invasive growth
o Anaplastic - poor cell differentiation
o Dysfunctional
o Commonly recur
Grading of malignant tumors
- if it is present: histologic analysis of degree of anaplasia (diverge from normal cell)
Staging of malignant tumors
- Description of location and pattern of spread
Tumor scale
- (local or invasive;1-4) higher worse
How to use Nodes for cancer
- (no, yes, distant; 0-3) see if cancer cells draining through them
Metastasis M0 M1
- (no, yes; M0- hasn't left the region, M1- other tissues)
Stage 0
- Carcinoma in situ.
Stage 1, 2, 3 cancer
- Higher numbers indicate more extensive disease: Larger tumor size and/or spread of the cancer beyond the organ in which it first developed to nearby lymph nodes and/or organs adjacent to the location of the primary tumor.
Stage 4
- The cancer has spread to another organ
Where does carcinogenesis derive from
- Tissue stem cells that can proliferate
What are 80-90% of cancers from?
- Epithelial
What induces 80-85% of cancers
- Carcinogens - risk factors
What can increase risk of cell turnover
- inflammation and injuiry
Lifestyle risk factors for cancer
- tobacco, obesity, diet, UV light
Occupational exposure risk for cancer
- benezene, herbicide, paint, asbestos
Oncogenic viruses that increase risk for cancer
- HPV, BCV
Initiation of cancer is usually cause by
- most are caused by mutation in growth control genes
Classes of genes that are involved in cancer initiation (DNA damage)
- Normal proto-oncogenes are over-active
- Tumor suppression genes (anti-oncogenes) are inactivated
Proto-oncogenes
- growth factors
- growth factor receptors
- intracellular pathway components
- transcription factors
- LEADS TO overactivation & inappropriate proliferation
prb gene
- master brake of the cell cycle, inhibits transcription (Abnormalities in gene cause heritable cancer)
p53
- p53: suicide gene, causes apoptosis of errant cells
WHat causes promotion of cancer
- Inactivation of prb and p53 genes
Cancer progression
- Excessive cell replication
- Cell immortality
- Increasingly undifferentiated & lack of function
- Invade adjacent tissues
- Travel to more distant sites
MEtastasis of cancer
- Process of spreading to sites distant from primary site
Why does metastasis of cancer matter
- prognosis & treatment
what is the pathe that metastasis follow? lymphatic or bloodstream
- lymphatic or bloodstream => predictable patterns of spread
What facilitates metastasis of cancer?
- Enzymes & receptors facilitate
Tumor markers
- Enzymes/proteins secreted by tumor cells
PSA
- Tumor marker for prostate cancer
CEA
- Tumor marker for colon cancer
CA125
- tumor marker for ovarian cancer
Clinical uses for tumor markers
- Diagnosis (not so good for this)
- Prognostic tool
- Assessing response to therapy
What is pain from in cancer
- usually asymtomatic until lethal
- erosion from cancer into the nerves or vessels
Effects of cancer on tn the host, cachexia
- tumor uses so much of the nurtrients that the body starves, or GI tract has problems, or nausea and vomitting
Effects of cancer on the host
- pain, cachexia, immunosuppression, infection, organ dysfunction, death
Normal Proliferation in Response to Infection of lymph
- bacterial infection it is expected more are formed
- Polyclonal- response from many different cells
Malignant Proliferation of lymph
- Monoclonal- stem cell that mutates, all derived from this one cell
- WBCs demonstrate poor functionality, impair production of other marrow cells and behave invasively.
Lymphoid leukemia and tumor marker
- malignant transformation of lymphocyte stem cell (NK, B cell, t cell)
- ALL or CLL
Myeloid leukemia
- AML or CML
- Malignant transformation of granulocyte stem cell (Neutrophil, monocyte, RBC, megakaryocyte)
Classification of hematologic disorders
- lineage (myeloid or lymphoid)
- specific cell type and specific genetic mutations or markers
- stage
If a test says Blast
- probably have a leukemia, so draw attention to that because it should only be in the bone marrow
Genetics, leukemia
- Chromosomal translocation of CML, form abnormal gene, chrome break and reattach, bcr abl gene
Lymphoma
- in the lymph nodes
Hodgkins lymphoma
- Young adults
- Spreads predictably
- Good prognosis in early stages
What cell is present in hodgkins lymphoma biopsy of lymph node?
- Reed sternberg cells
Non hodgkins lymphoma
- Adults
- lymph node biopsy - Categorized according to cell type
- Unpredictable
- Poorer prognosis
Symptoms of lymphoma
- weight loss
- night sweats
- intermittent fevers
- Cancer, HIV and tuberculosis
Plasma cell myeloma
- set up in bone, but in blood stream making the antibodies
- lymphoid malignancy
- plasma cells proliferate
- monoclonal antibody
What is found in plasma cell myeloma
- bence jones proteins in urine
- monoclonal antibody peak on serum electrophoresis
Manifestations of plasma cell myeloma
- bone pain and pathologic fractures- break without reason
- high serum calcium because of bone destruction
Cancer therapies: Primary
- Surgery and adjunct therapies
Antineoplastic drug therapy:
- Chemotherapy
- Biologic Response Modifiers/Tissue specific therapies (target the particular difference of a cancer cell (e.g. BCR-ABL in CML)
Treatment of cancer
- Primary, antineoplastic drug therapy, radiation, bone marrow or stem cell transplantation, gene therapy
Chemotherapy
- cytotoxic, especially to rapidly dividing cells
- must be dividing to be affected
- toxic to normal cells as well
- requires multiple courses
Type of cancer that is harder to kill
- slow growing
What is chemo better for (cancers)
- of blood, lymph, and small solid tumors
What may develop in response to chemo?
- tumor resistance
Toxic effects of chemo
- Bone marrow suppression -• Leukopenia, neutropenia, anemia, thrombocytopenia
- Gastrointestinal effects
- N/V; Stomatitis
- Alopecia
- Altered sexual/reproductive functioning (often sterility)
- Organ toxicities
Mab biologic response modifiers for cancer
- block growth factors, apoptosis
Nibs biologic response modifiers for caner
- angiogenesis inhibitors, hormone agonists
NEURO
...
Seizures: Acquired
- brain injury, temperature, withdrawl
Seizures: Idiopathic
- don't know why they are happening
Seizures: Pathogenesis of seizure
- "Cerebral storms"
- Epileptogenic focus
- Triggering stimulus
Diagnosis of seizure
- EEG
What to do when someone has a seizure
- Observe, document, protect
Partial seizure
- only in one hemisphere of the brain
Status Epilepticus
- prolonged or repeated seizures without recovery
Most frequent cause of seizure
- drug noncompliance
how to medically terminate a seizure
- fast acting bezodiazepines IV - increase GABA
- lorazepam (Ativan), or diazepam (Valium)
- Then, IV phenytoin (Dilantin) (loading, then maintenance dose)
Migraine
o + aura- know it is coming on, maybe squiggly lines
o throbbing
o unilateral
o generalized N+V
o seek dark, quiet
Who is more likely to have migraines
- women menses
How to treat migraines (drug)
tryptans
Cluster
o Severe, episodic
o No throbbing forehead, eye
o Eyes tear, ptosis pace
o Beat head
o Seasonal
o Rare, inflammation on one side, autonomic system
Who is more likely to have cluster?
- men
Tension
o Constant
o No throbbing
o Tight band
o Bilateral
o Not worse with activity
What to do:
Very acute onset of headache, "first, worst
- evaluate
What to do:
Stiff neck
- evaluate
What to do:
can't wake up
- Eval
What to do:
Papilledema or hemorrhage of the ocular fundus
- Eval
First happens with bacterial menigitis
- infection in nasopharyngeal first
Unusual part about bacterial menigitis
- significant bacteremia- bacteria in the blood stream
Bacterial meningitis
- Bacteria gain entry to CSF via areas of low BBB like choroid plexus
- Bacteria proliferate in CSF, cause symptoms and activate immune cells
- Inflammation causes cerebral edema,
How is bacterial meningitis treated?
- steroids and antibiotics
S/S of bacterial meningitis
- Headache, stiff neck (nuchal rigidity), fever, changes in LOC, CSF high in protein and WBC, low in glucose.
Ischemia, what may cause
- swelling or sodium k pump may also cause the cells swell
Primary ischemia
- killed from initial injury
Secondary ischemia
- Reperfusion causes cells to kill the damaged cells
Normal ICP
- 15mmhg
What takes up space in the brain
o Blood
o Brain tissue
o Cerebrospinal fluid (CSF)
How ICP componsate
o CSF shunt to spinal cord
o Hyperventilation leading to vasoconstriction
o That's it! Brain tissue can't get smaller without damage!
Contributors to Elevated ICP
Blood:
right heart failure, increased abdominal/thoracic pressure (Valsalva), hypoxia, increased PaCO2 & acidosis
Contributors to Elevated ICP
Brain tissue
- tumor, hematoma, infection, ischemia, cytotoxic & vasogenic cerebral edema
Contributors to Elevated ICP
Cerebrospinal fluid
- Hydrocephalus- too much CSF
Cushing response
- Intense increase in ICP these "last ditch" efforts by the body to establish blood flow to the brain (impending herniation) because blood flow is restricted
Manifestations of cushing response
- Markedly elevated systolic pressure
- Widening pulse pressure
- Decreased heart rate
- Herniation is the potential ultimate result
Eval of acute brain injury ICP
- ABC
- Neuro (LOC and s/s)
- CT scan immediately
S/S of increased ICP
o vomiting; pupil & vision changes (PERRLA); changes in motor function (weakness, drift, posturing), and VS (Cushing's response)
Interventions for Increased ICP: Maintain Cerebral Perfusion
- Control fever & pain - Don't want them using metabolic activity
- Decompression surgery, ventriculostomy
- Mild lowering of PaCO2- hyperventilate to get them to vasoconstriction
- Oxygen
- Hypothermia, rest, pain & seizure control
- HOB elevated, neutral body position- in order to drain
Interventions for Increased ICP: Maintain Cerebral Perfusion - drugs
- Osmotic diuretics (mannitol)
- Barbiturate coma (pentobarbital)
- Seizure prophylaxis (phenytoin)
TBI : Coup (focal)
direct
TBI : contra coup
- Head has hit something and sloshed back and forth, whiplash
Diffuse TBI
- widespread
Contusion
- disruption of the blood
- brain bruise
Concussion
- neurons have been injured, but can't see any evidence of that
Intercranial hematoma
- bleeding
Skull fracture
- open head injury, worry about infection getting into the brain
Concussion: Grade 1
- transient confusion, no loss of consciousness, symptoms resolve in 15 min
Concussion: Grade 2
- transient confusion, no loss of consciousness, symptoms last longer than 15 min
Concussion: Grade 3
- any loss of consciousness
Hematomas- Epideral hematoma
- usually arterial, bleeding is fast, go downhill fast
Hematomas- Under the dura
- likely to be venous, bleed slowly 2-3 wk later
Hematomas -Sub dura
- bad shape from the beginning, not as easy to take out
Hematomas- subarachnoid
- no trauma, just ruptures
Risk for Stroke
o Age, >70% of strokes in those > 65 years
o Atherosclerotic risk factors
o 70% of strokes have associated hypertension
o Atrial fibrillation: 6-fold risk for stroke
thrombotic stroke
- forms in the place it happens, ischemic
- 80%
- Athersclerotic risk factor
- TIA
What has a 6 fold risk for stroke
- A Fib
TIA
- (looks like they're having a stroke, but it goes away after a while) precedes stroke in about 60% of cases
- Infarction after 1 hour of symptoms
Embolic stroke
- from elsewhere in the body
- atrial fibrillation, valvular disease, hyper- coagulable states
Hemorrhagic stroke
- BV pops
o structural anomalies (AVM, aneurysms)
o Hypertension
o More than 60 ml bleed associated with 70-90% mortality.
Ischemia, blood flow
- If local flow < 20 ml/100g
Infarctions, blood flow value
- If local flow < 12 ml/100g
Secondary injury in stroke
- inflammation and apoptosis
Penumbra
- zone of injured but potentially salvageable tissue, what we want to save and reperfuse
Acute manifestations of stroke
o focal neurological signs
o may rapidly change (evolve)
o depends greatly on area of brain damage
General manifestations of stroke
- Deterioration of LOC
- Loss of bowel &/or bladder function
- Contralateral ptosis (drooping eyelid)
- Dysphagia
- Homonymous hemianopsia- loose part of their visual field
Manifestations Unique to Hemorrhagic Stroke
- Abrupt onset & explosive H/A, occipital or nuchal - Headache
- Rapid decrease in LOC
- Photophobia
- N/V
- Nuchal rigidity
- Seizures
Management of stroke, Ischemic
- Thrombolytic therapy
management of stroke- Hemorrhagic
- BP management
- surgical and invasive interventions
what is a risk for a stroke
- Heart attack
Dementia
- deterioration of memory and cognition
Most common dementia
- Atlzheimer, vascular dementia
Manifestations of Alzheimer
o Decline in judgment - Confusion
o Loss of affect - Disorientation
o Memory impairment
Mild cognitive impairment
- Decline in mental function w/out compromising independence
Preclinical Alzheimer
- No symptoms but recognizable atrophic brain changes
Diagnosis of Alzheimer disease
- First investigate other, treatable causes of dementia)
- Depression, substance abuse, vision and hearing deficits, electrolyte imbalance, infections, drug side effect, hypoxia
Anticholinesterases
- modest effect on slowing mental deterioration (probably not disease modifying
- donepezil (Aricept), galantamine (Razadyne), rivastigmine (Exelon), tacrine (Cognex)
NMDA receptor blockers may help symptoms Alzheimers
- Glutamate (NMDA receptor) inhibitors
- memantine (Namenda)
- Investigational: gene therapy with nerve growth factor injected into brain
Etiology of Parkinsons
- some suspect pesticide exposure
- MPTP cases of Parkinson-like syndrome
- Oxidative stress from DA metabolism by MAO in substantia nigra
Pathogenesis of parkinsons
- Low dopamine level in basal ganglia
- Excessive action of acetylcholine
- Disease process is progressive
- Early onset: parkin gene and a-synuclein gene (Maybe genetic)
Classic triad of Parkinsons
♣ Akinesia- delayed talking, delayed motor
♣ Rigidity - Stiff
♣ Resting tremor
Associated manifestations: Parkinsons
♣ Propulsive gait - can't adjust- Poor speech quality
♣ Masklike face - 30-50% have dementia
♣ Drooling- trouble swallowing
Management of Parkinsons
♣ MAOI (selegiline)
♣ Amantadine (Symmetrel)
♣ Levodopa, carbidopa (Sinemet)
♣ Dopamine agonists e.g. bromocriptine, pramipexole (Mirapex); Ropinirole (Requip)
♣ anticholinergics (Cogentin, Artane)
Levodopa/carbadopa
o levodopa: a dopamine precursor
♣ Crosses BBB, then converted to dopamine in the CNS
o carbidopa: blocks peripheral breakdown more levodopa to reach the CNS
o Functions as a precursor to DA production in the neuron to enhance release, but doesn't appear to slow the course of the disease.
Myalgia
- Muscle pain
Myalgia, Transient
- overuse, injury, viral and strain
Transient types of myalgia
- Drug-related myalgia - Cholesterol lowering agents (statins, fibrates) cause injury to muscles
- Fibromyalgia Wide spread muscle ache
- Immune-mediated disorders (overlap among them)
Actue myalgia
♣ Rhabdomyolysis (release of myoglobin into blood, can damage kidneys)
Systemic Lupus Erythematosus
- Autoimmune- Type 3
- inflammation of connective tissue
- drug induced variation
Systemic Lupus Erythematosus
manifestations
o -Polyarthritis/arthralgia -Photosensitivity
o -Frequent fevers -Alopecia
o -Fatigue -Butterfly rash
o -Organ failure -ANA antibodies For diagnosis
Rheumatoid arthritis
- Chronic, systemic, autoimmune, inflammatory
- symmetrical
-
Process of RA
- Ongoing inflammation panus formation ankylosis
Diagnosis of RA
- Rheumatoid Factor, elevated ESR, x-ray changes -Antibody to look for if person has it, for diagnosis
Treatment of RA
- ASA/NSAIDs, steroids; Disease Modifying Anti-rheumatic Drugs (DMARDs) (methotrexate; etenarcept [Enbrel])
Panus
- goo inside of joints
Osteoarthritis
o Progressive, non-immune disease of joints, especially weight bearing, DIP joints
o Localized "wear & tear"
Osteophytes & crepitus
bones grind
treat osteoarthritis
- o Acetaminophen; NSAIDs; COX-2 inhibitors
o Glucosamine & chondroitin
o Physical therapy & weight loss
o Joint replacement surgery
Osteoporosis/Osteopenia
- brittle bones, demineralization of bones
Treatment of Osteoporosis/Osteopenia
- ♣ Bisphosphonates: alendronate (Fosamax), ibandronate (Boniva); zoledronic acid (Reclast; Zometa) can form bone, but body can't break it back down, permanent
♣ teriparatide (Forteo) to not take calcium out of the bone
♣ Selective Estrogen Receptor Modulators (SERMs): raloxifene (Evista)
Types of fractures
- o (trauma; stress fractures; pathologic fractures no reason for breaking)
Delayed union
- more than 3 months to heal
malunion
misaligned healing
osteomyelitis
- infection of the bone
• Difficult to treat
• Sources: open fractures, surgery, other
• Initiates inflammatory response
osteomyelitis treatment
o Antimicrobial therapy
o Possible bedrest
o Debridement, bone grafts, implants
Fat emboli
- bone marrow gets into the blood and can cause pulmonary embolism, or blood clots
- long bones
- pressure and trauma fat droplets into venous system
Compartment syndrome
- inflammation cuts off blood supply, cast on too early, or can cut off its own blood supply by faciae
Compartment syndrome s/s
- ♣ pain
♣ pulseless
♣ pale
♣ paresthesia
♣ paresis
♣ "polar" (cold)
Injury to upper neurons
o Hyperreflexia
o + Babinski -Stick out big toes except adults curl normally
o Spasticity, clonus
o Hemiplegic paralysis or paresis
o Late atrophy (disuse)
Injury to lower motor neurons
o Hyporeflexia or areflexia
o Flaccidity - no tone
o Paralysis or paresis of individual muscles in spinal/peripheral nerve distribution can't move it
o Early atrophy (denervation)
"complete" versus "incomplete
- lose some on one side and not on the other)
Spinal shock
- last hours to weeks
- loss of all sensory
- skeletal muscle flaccidity
- atonic bowel and bladder
Recovery of spinal shock
♣ ignaled by return of spinal reflexes
♣ Incomplete - mixed deficits
♣ Complete - no sensation & spasticity below level of injury
Neurogenic shock
o Type of distributive shock
o Cervical & upper thoracic injuries only (T6 level & above)
o Loss of sympathetic outflow (=> PSNS domination)
- unable to vasoconsrict when upright
Neurogenic shock, loss of sympathetic outflow
♣ Peripheral vasodilation => severe hypotension
♣ Bradycardia
♣ Often hypothermia
Helping with neurogenic shock
o need lower extremity compression, slow position changes
Autonomic dysreflexia
o Life threatening chronic problem for T6 and above (rare below)
o Reflex activation of sympathetic neurons below level of injury
o Stimulus induced event (reflex) => rapid response
Autonomic dysreflexia s/s
♣ Profound hypertension
♣ Headache & possible blurred vision
♣ Bradycardia
♣ Above SCI - flushing & diaphoresis
♣ Below SCI - pallor, cool clammy skin, piloerection
Multiple sclerosis etiology
♣ Autoimmune
♣ Viral trigger with genetic predisposition
Multiple sclerosis pathogenesis
♣ Immune injury to myelinated neurons in the cord and the brain
♣ Sclerotic plaques and demyelination noted on MRI
♣ Demyelination disturbs neuron conduction
Multiple sclerosis s/s
♣ Highly variable
♣ Relapsing-remitting most common
♣ Common manifestations
• Fatigue
• Visual disturbances
• Weakness, paresthesias, spasticity
• Bowel/bladder dysfunction
• Pain
• Mood swings; depression
• Cognitive impairment
Peripheral neuropathy
- Affects one or more peripheral nerves
Peripheral neuropathy: sensory changes
- tingling, numbness, pins and needles, loss of sensation, pain and/or
Peripheral neuropathy: Autonomic
orthostatic hypotension, altered sweating, altered GI motility, erectile dysfunction
Peripheral neuropathy: motor
flaccid weakness, atrophy, reduced/absent DTRs, paralysis or paresis
Myasthenia gravis
o Insidious onset, Autoimmune
o Antibodies bind to Ach receptors in NM junction and block activity
o Progressive weakness & fatigue
o Muscles of eyes, face, eating & speech usually first
o ptosis, diplopia, head droop, jaw drop
Major concerns of Myasthenia gravis
o dysphagia & decreased respiratory function
Myasthenic Crisis versus Cholinergic Crisis
• MC = not enough drug (exacerbation)
• CC = too much drug
• Differentiated with response to edrophonium
Myasthenia Gravis treat
- Long-term management with long-acting anticholinesterase drugs - neostigmine (Prostigmin) or pyridostigmine (Mestinon)
- ADRs: N/V, diarrhea, miosis, bradycardia
PAIN
...
When nerves are stimulated
Inflammation and injury
Transmission of pain A delta and Cfiber
♣ A delta fast pain
♣ C fiber slow pain throbbing not very localized, tissue damage, hard time handling, PTSD
♣ Follows a dermatome
perception, lower brain centers
RAS, can ignore it like sitting down
Perception, thalamus
- relay station for pain signals
Perception, cortex
• Primary sensory cortex
• Cortical association area- where chronic pain is, effects everyday events (anxiety, depression)
• Limbic structures- emotional connotations like pain, long memory of pain, where acute pain is activated
modulation of pain at nociceptor
♣ Cold
♣ Massage
♣ Drugs (ASA/NSAIDs, local anesthetics)
modulation of pain at spinal cord
♣ Endogenous endorphins & enkephalins
♣ Drugs (morphine; epidural & intrathecal analgesia)
♣ Devices based upon gate-control theory (TENS; DCS) compete at synapses
♣ Massage
modulation of pain at brain
♣ Endogenous endorphins & enkephalins
♣ Drugs (Opioids, ASA/NSAIDS, acetaminophen, adjunct Rx)
♣ Biofeedback; guided imagery; yoga; distraction
Neuropathic pain syndromes, where are they
- trigeminal nerve, not at receptor
Neuropathic pain syndromes examples
o post-herpetic people who had shingles that have gone away
o diabetic peripheral neuropathy
o low back pain
o Phantom limb pain
Analgesia Routes & Methods
Enteral
♣ Oral (pills, tablets, extended; spray)
♣ Sublingual and buccal swabs
Analgesia Routes & Methods
topical
o for people that have tolerance to narcotics, not as much first pass effect
♣ transdermal patches & rectal suppositories- systemic
Analgesia Routes & Methods
Parenteral
♣ IM & subcutaneous rarely utilized
♣ IV & Patient Controlled Analgesia (PCA)
♣ Epidural & implanted intraspinal reservoirs
♣ Intraarticular
♣ Nerve blocks
opioid receptors
- G-protein linked receptors (inhibitory)
Use for opioid
mild to severe pain cross BBB
opioid in spinal cord and brain
♣ Pure agonist
♣ Agonist-antagonist/partial agonist - can compete with heroin etc, person can go into withdrawls
♣ Antagonist (block mu & kappa)
Opioids for mild to moderate pain
♣ codeine (Schedule II to V)
♣ propoxyphene & combinations
Opioids for moderate-severe pain
♣ morphine
♣ hydrocodone (combinations)- oral and usually in combo
♣ oxycodone (combinations; extended release OxyContin)
♣ fentanyl (Sublimaze)
♣ hydromorphone (Dilaudid)
♣ methadone
For opioid comparison
compare to morphine doses
ADRS of opioids
o Tolerance will develop
o Dependence a concern w/ prolonged use
o ADRs due to negative results of receptor stimulation
♣ Hypersensitivity rxns; pruritus, rashes; orthostatic hypotension; respiratory depression, N/V, constipation, urinary retention, miosis, CNS depression (safety!)
Non-opioid Analgesics
- NSAIDS
- Asprin
- Acetaminophen
Emprin
- Tylenol/ ASA with codeine
percodan
- oxycodone with ASA
percocet
- acetaminophen with oxycodone
darvocet
- prooxyhene with acetaminophen and caffine
vicoden
hydrocodone and acetaminophen
naloxone HCL (Narcan)
o competes with the narcotics, need consistent dose to maintain
Opioid Antagonist (Antidote)
naloxone
buprenorphine and naloxone combo (Suboxone)
This combo is being used as replacement narcotic for addicted individuals (instead of methadone) because it discourages crush and IV injection.
Elder and pediatric issues of opioids
♣ Assessment challenges
♣ Effect of aging on pharmacokinetics
♣ Increased sensitivity to drug effects
♣ Heightened risk for interactions & ADRs
Benzodiazepines
- Bind to GABAA receptors and enhances GABA action on the receptor. The GABAA receptor is a chloride ion channel. When open it inhibits neuronal depolarization (GABA is the main inhibitory NT).
bezodiazepines, uses
General depression of neurotransmission, so is useful in anxiety, insomnia, seizure, etc
bezodiazepines, additive effects with
o alcohol, narcotics)
bezodiazepines, examples
diazepam (Valium), lorazepam (Ativan), alprazolam (Xanax).
Sleep Agents (hypnotics)
o Generally less CNS depression, less abuse potential than Benzo.
Sleep Agents (hypnotics), names
o Zolpidem (Ambien)
o Eszopiclone (Lunesta)
o Diphenhydramine (Benadryl)
Barbituates
- was anxiety and sedation now for seizures
- Similar mechanism of action on GABA receptors as benzos.
Barbituates, Drug interactions
- Notorious P450 enzyme-inducer, which leads to numerous drug interactions
Amphetamines, drugs
- Amphetamine apartate (Adderall)
- Methylphenidate (Ritalin, Concerta)
NE reuptake inhibitor
- less dangerous, inhibit reuptake of norepi, now more is available
NE reuptake inhibitor, drugs
- Atomoxetine (Strattera)
Serotonin Agonists (migraine agents)
- bind to serotonin receptors and stimulate
Tricyclic mechanisms
- (NE, DA, 5HT reuptake inhibition)
MOA of antiseizure agents
- Affect ion channels and inhibit AP initiation and conduction
Antiseizure agents, drugs
♣ Phenytoin (Dilantin)
♣ Carbamazepine (Tegretol)
♣ Valproic Acid (Depakote)
Antiepileptic Drugs
o Individualize drug treatment
o Single agent or combination therapy
o Monitor adverse effects
o Usually drug serum levels monitored
o Discontinued by tapering dosage, may cause seizures
Anterolateral (spinothalamic), sensory nerve tracts
o Crosses immediately in the cord, contralateral
o Sensation is poorly localized
o Itch, pain, temperature
Dorsal column, sensory nerve tract
o Ipsilateral until medulla, then crosses
o Sensation is well localized
o Fine touch, vibration, pressure
corticospinal motor nerve tracts
o Crosses at medulla
o Innervates distal muscles -the ones with fine motor control
o Fine motor control - write, play the keyboard
Extrapyramidal or medial, motor nerve tracts
o Some cross at medulla, some do not
o Innervates proximal muscles
o Balance, posture & gross motor
Your patient tells you that her brother has hemophilia and she is concerned about being a carrier. What is the risk?
50%
Anemia associated with a low reticulocyte count is likely related
Iron deficiency, problem with production
Which type of anemia is microcytic, low mcb?
Iron deficiency
A patient with a high erythropoietin probably has which type of polycythemia
Secondary
Pernicious anemia is associate with
Vitamin B12, Elevated MCV, big cell, macrocytic
Which laboratory result would explain the finding of jaundice in a patient?
Hemolysis
A patient with a significantly elevated bilirubin probably has
Jaundice
You are assigned to a patient who takes 5 mg of Coumadin and note that he has blood in his urine. Which lab should be being monitored in his chart
a. PT/INR
Patient has inr of 1.5. what does this mean?
a. It is not likely to be the cause of the bleeding
Life span of a RBC
120 days
A patient with a hematocrit of 35% and a hemoglobin of 8 mg/dl probably has an erroneous result
TRUE
A platelet count of 90,000 is normal
False thrombocytopenia
Your renal dialysis patient's labs include Hct 33% hgb 11 mg/dl all indicies WNL what is likely etiology
a. Erythropoeitin deficiency
When doing your clinical prep you find that the patient has stage 0 cancer. What does this mean?
The cancer is in situ
Defective tumor suppression genes are heritable
Malignant
Gain of function mutations in --- are associated with cancer initiation or progression
a. Proto- oncogenes
b. Loss of - rb protein genes, Apoptotic, tumor suppression
The TNM stage for your patient with cancer is listed as T3 N2 M1 meaning
There is distant metastasis, look at M1, also means stage 4
Large quantities of monoclonal antibodies in the blood are indicative of
a. Plasma cell myeloma
A monoclonal antibody against BCR ABL would be useful for treating
CML
Your patient is initiating chemotherapy for breast cancer. What lab can you expect to monitor closely?
CBC, look at blood levels (platelets)
1. Your patient is receiving filgrastim Neupogen post chemotherapy you expect this drug to
Increase granulocyte production
1. Which of the following is the most seious and concerning finding in your patient who is undergoing radiation and chemotherapy for cancer?
a. Temp 100.9
b. Nausea and vomiting
c. Pain at biopsy site
d. Stomatitis
a. Temp 100.9- reason people die of cancer is infection
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