Clinical Medicine Flashcards
What are the different types of radiation used for therapy?
Ionizing radiation - electromagnetic (x rays, photons) or particulate (electrons, protons, neutrons, charged particles)
What are the two general uses of radiation in cancer treatment?
Used for local treatment, targeting area of known disease plus margin of normal tissue
Treats area of most likely local/regional spread of disease
What are the units of measurement for radiation exposure?
Orthovoltage/supervoltage
Roentgen - related to ability of x rays to ionize air
Rad - unit of absorbed dose, absorption of 100 ergs/g
Gray - energy absorption of 1 joule/kg
What is the mechanism of radiation effects on tissue?
Directly ionizing - charged particles can disrupt atomic structure of absorber and directly produce chemical and biological changes
Indirectly - electromagnetic give up energy to absorber to produce charged particles
Where in the cell does treatment of cancer act?
Photon interacts with atom or molecule which produces ion radical which produces free radical which damages DNA
Single or double stranded breaks but double more important
Repair not as efficient in cancer cells
What are the four modifiers of the radiation response?
Cell cycle
Type of radiation
Oxygen enhancement
Fractionation
How does the cell cycle enhance the effects of radiation?
Cells most sensitive to radiation in m and g2 phase
Least sensitive in late s phase
Intermediate sensitivity in g1 and early s
Drugs that increase proportion of cells in m and g2 will increase effects of radiation
How do types of radiation enhance effects of radiation?
Densely ionizing radiation (alpha particles or low energy neurons) - survival exponential function of dose, compact area
Sparsely ionizing radiation (x rays) - dose response curve is initial linear, then shoulder, then becomes straight at high doses, more spread out - less likely to hit DNA
How does oxygenation enhance the effects of radiation?
Cells more sensitive to radiation when they are in oxygen rich environment
Large tumors outgrow blood supply and cause central hypoxia - radiation kills peripheral better
Drugs that increase oxygen content can increase radiation response
How does fractionation enhance the response to radiation?
Single dose of radiation has greater kill than same dose in multiple smaller fractions due to repair of sub lethal damage b/w doses
Therapy is a balance - multiple smaller doses preferred
What are the four different fractionations?
Standard - once a day, 5 days per week
Hyperfractionation - decreases dose per fraction and increases total dose delivered
Accelerated fractionation - decreases total treatment time with no changes in number of fractions, total dose or dose/fraction
Accelerated hyperfractionation - combo of both altered schemes
What are the early side effects of radiation therapy?
Occur within days or weeks in tissues with rapid turnover
Rapidly repaired and may be reversible
CNS - fatigue, nausea, hair loss, swelling
Head and neck - dry mouth, taste change, skin irritation
Thorax - esophagitis, pneumonitis, pericarditis
Abdomen - nausea, vomiting, nephritis, hepatitis
Pelvis - diarrhea, dysuria, bone marrow suppression
What are the late effects of radiation therapy?
After months of years on slowly proliferating tissues
May improve but never completely repaired
CNS - damage to brain tissue
Head and neck - permanent xerostomia, osteoradionecrosis of mandible, myelitis
Thorax - fibrosis, myelitis
Abdomen - necrosis of small bowel, kidney, liver
Pelvis - hematuria or rectal bleeding, fibrosis
What are the two methods of delivery of radiation?
Teletherapy = external beam irradiation - radiation generated with electricity, electrons accelerated then rapidly decelerated in target material to produce x rays, directed at tumor from outside body - if not on surface multiple beams directed to intersect at site (target volume)
Brachytherapy - radiation source placed in body, mostly in GYN malignancies esp cervical cancer, intracavitary or interstitial
What are the three general categories of info required to make treatment decisions for cancer patients? What do you use to do this?
Site and extent of disease
Type of tumor
Patient characteristics that may limit possible treatment methods
Histopathology and stage
What are petechiae pathognomonic of?
Thrombocytopenia
What are special areas to pay attention to on physical exam of a bleeding disorder patient?
Skin and mucous membranes (mucous membranes could indicate CNS involvement - bad)
Spleen
Lymph nodes
Joints
What are disorders of primary hemostasis characterized by?
Early bleeding
Mucocutaneous bleeding
Abnormal platelet count, function or morphology
Failure to stop bleeding after initial injury
What platelet count is considered low?
Less than 10,000
What is pseudothrombocytopenia?
Artifactual clumping of platelets in response to EDTA in collection tube
Uses different tube to rule out
How does platelet volume help clue the cause of thrombocytopenia?
Young platelets and those produced during periods of high turnover are larger
What are the three broad causes of thrombocytopenia?
Decreased production
Increased destruction
Sequestration
What are causes of decreased platelet production and what would you see on peripheral blood smear?
Bone marrow infiltration - see dacrocytes
End stage cirrhosis - deficiency of thrombopoietin - see spur cells
Nutritional - b12 or folate deficiency, iron deficiency
Sepsis
What are some causes fond increased destruction of platelets?
Immune thrombocytopenia (ITP) DIC TTP HUS Vasculitis Will see schistocytes
What should you look for in the peripheral smear of thrombocytopenia?
Platelet clumping at feather edge - rule out pseudothrombocytopenia
Schistocytes –> microangiopathic process w fibrin deposition
Dacrocytes and nucleated RBCs –> bone marrow infiltrate
Spherocytes and microspherocytes –> ITP
Macrocytosis - liver disease?
Microcytosis, hypochromia
What is ITP and how is it diagnosed?
Development of antibodies against platelets
HIV individuals have high incidence
Testing for antibodies not helpful for diagnosis
Diagnosis of exclusion - physical exam and blood tests normal
What are the classifications of ITP?
Autoimmune - primary (classic, HIV related, hep c related) or secondary (SLE, lymphoproliferative disorders, solid tumors)
Drug induced
Infection induced post transfusion purpura
Neonatal isoimmune
Aloo immune
How does drug induced thrombocytopenia happen?
Drugs induce anti platelet antibodies that are dependent on presence of drug
What is heparin induced thrombocytopenia?
Virulent form of thrombocytopenia associated with high risk of arterial and venous thrombosis
Antibodies against platelet factor 4-heparin complex that activates platelets
Diagnosed by measuring HIT antibodies
What are signs and symptoms of acquired platelet function disorders?
Superficial ecchymoses out of proportion to any degree of trauma
Which drugs can cause acquired platelet function disorders? What else can cause them?
Aspirin and NSAIDs
Calcium channel blockers
Renal failure and uremia
Liver failure
What are four inherited qualitative platelet disorders?
Glanzmann thrombasthenia
Bernard soulier syndrome = giant platelet syndrome
Pseudo Von willebrand disease
Storage pool deficiencies, gray platelet syndrome
What are the two functions of vWF?
Bridge between platelet glycoprotein and vascular endothelium
Transport protein for factor VIII
What are the feature of Von willebrand disease?
AD abnormal quantity (type 1) or quality of vWF (type 2) easy bruisability and mucosal bleeding Prolonged PTT Factor VIII may be low
How is Von willebrand disease diagnosed in the laboratory?
Non specific tests - bleeding time, Pfa 100 and PTT
VWF antigen - immunoassay to detect vWF protein
*Ristocetin cofactor assay is quantitative measure of vWF activity
Ristocetin induced platelet aggregation could be abnormal
Multimeric analysis
How can scurvy be recognized?
Unusual pattern of hemorrhage which occurs adjacent to and encircling each individual hair follicle giving stippled appearance
How can you recognize leukocytoclastic vasculitis?
Palpable purpura
Purple nodules or crusts that can be felt
What is henoch-schonlein purpura (HSP)?
Leukocytoclastic vasculitis in children that begins with urticarial plaques on trunks, scrotum, and lower extremities
Arthralgias and abdominal pains common
How can you recognize hereditary hemorrhagic telangiectasia (osler-weber-rendu disease)?
Multiple dermal, mucosal, and visceral telangiectasia and frequent nosebleeds and mucosal bleeding
What are secondary disorders of hemostasis characterized by?
Delayed onset, deep tissue and joint bleeding, and deep hematoma
What tests assess the intrinsic pathway vs the extrinsic pathway of coagulation?
Intrinsic assesses by PTT
extrinsic assessed by PT
Why is factor VII the most sensitive vitamin k dependent clotting factor?
It has the shortest circulating half life in plasma
What is disseminated intravascular coagulation?
Inappropriate coexistence of fibrin generation and fibrinolysis with global consumption of clotting factors
Fibrin strands sheer erythrocytes = microangiopathic hemolytic anemia
Thrombocytopenia almost always present
How can DIC be recognized easily?
Bleeding from venipuncture and IV sites
May develop confluent purpura, including conjunctival hemorrhage
What are the clinical settings of DIC?
Sepsis
Malignancies
Obstetrical disasters
Trauma - crush injury, brain injury, burns
What are the two possible diagnoses if all PT/INR, TT, and PTT are all normal but you still suspect a plasma coagulation defect?
Factor XIII deficiency
Amyloidosis
What two factors are valuable to measure when attempting to diagnosis DIC?
Fibrinogen degradation products (FDP) and d dimers
FDP low and d dimers high probably indicates
How you check for acute bleeding?
Tilt test
Orthostatic BP and pulse rates
How can you check for on going bleeding?
Stool guaiac
Gastric lavage
Urinalysis
What are the “chronic diseases” meant by ACD?
Inflammation or cancer
What are the serum iron, TIBC, % saturation and ferritin level parameters in iron deficiency?
Decreased serum iron
Increased TIBC
very decreased saturation
Very decreased ferritin
What are the serum iron, TIBC, % saturation and ferritin level parameters in ACD?
Decreased serum iron
Decreased TIBC
decreased or normal saturation
Normal or increased ferritin
What are the serum iron, TIBC, % saturation and ferritin level parameters in thalassemia?
All normal except possible increased ferritin
What are the serum iron, TIBC, % saturation and ferritin level parameters in sideroblastic anemia?
Increased serum iron
Normal (or decreased) TIBC
Normal or increased saturation
Normal or increased ferritin
What are the 7 big causes of macrocytic anemia?
Folate and vitamin b12 def Liver disease Alcohol Bleeding Hypothyroidism Myelodysplasia Drugs
What are some clinical findings in the category of hemolytic anemias?
Increased bilirubin
Elevated serum LDH
absent serum haptoglobin
Increased urine urobilinogen
What is SVC syndrome?
Obstruction leads to collateral venous formation (azygous)
Symptoms are dyspnea, facial and arm swelling, cough, cyanosis
Commonly caused by lung, lymphoma, or breast cancer (right sided tumor especially)
What is Horners syndrome?
High apical tumors of lung
Symptoms are myosis, anhydrosis, and mild ptosis
Neuroblastoma in the infant can cause this
What at presentations of spinal cord compression?
Pain, weakness, paresthesia, bowel or bladder dysfunction
What are the two types of lactic acidosis caused by tumors?
Type b from increased pyruvate production
Type a from poor tissue perfusion
Usually in leukemias, lymphomas, or liver metastases
How does hypocalcemia occur in cancers?
Part of tumor lysis syndrome
Calcium binds to phosphate released by dying cancer cells
Rare - usually with leukemias or lymphomas
How does hypercalcemia in cancer patients present?
#1 metabolic emergency Dehydration, nausea, vomiting, weakness, confusion, coma, seizure
What is the pattern of primary hyperparathyroidism?
Increased serum calcium
Decreased phosphorous
Increased urinary cAMP
What is the usual hormone released by lymphomas?
Vitamin D3
What is humoral hypercalcemia of malignancy?
Primary tumor produces hormones released into circulation causing indirect release of calcium from bone without metastases
What cytokine can lead to local osteolytic hypercalcemia?
IL-1
IL-6
How is hypercalcemia in cancer patients diagnosed?
Serum protein electrophoresis
What is dermatomyositis?
Inflammatory myelopathy with proximal muscle weakness
Erythema of eyelids, telangiectasias on knuckles, chest and face
10% associated with lung or breast malignancy
Diagnosed with EMG/NCV to assess neurologic function
What is eaton-lambert syndrome?
Proximal muscle weakness 60% have underlying cancer, mostly small lung cell Antibody to presynapic calcium channels Improves with repeated contraction Diagnosed with EMG/NCV
When are radiologic studies used to evaluate the cancer patient?
Describe location, relationship to other structure, dimension, solid vs cystic, vascularity, approach to biopsy or resect
What kinds of radiologic studies are used for which area of the body?
CT scans for chest, abdomen, brain
Plain films for lungs and bone
MRI for spinal cord and brain
Sonography for abdomen and pelvis
What are the six common presentations of acute leukemia?
Anemia
Thrombocytopenia
Neutropenia
Leukostasis - blasts clog vasculature in CNS or lungs
Tumor lysis syndrome - can lead to uric acid neuropathy and renal failure, may be life threatening hyperkalemia and acidosis
DIC - especially common with APL
What are the phases of acute leukemia treatment?
Induction phase - goal is remission
Consolidation - eliminate remaining cells
Maintenance - for ALL but not AML
What’s an extra step in treatment needed for ALL and why?
CNS prophylaxis because of high incidents of CNS involvements
What is the Ann Arbor staging system for lymphoma?
Stage I - one group of lymph nodes involved
Stage II - two groups of lymph nodes on same side of diaphragm
Stage III - at least two groups on opposite sides of diaphragm
Stage IV - involvement of other organs like liver or bone marrow
Done with CT scans and bone marrow biopsy
What is rituximab and with which disease is it generally given?
Anti cd20 antibody
Diffuse large B cell lymphoma
