Flashcards in Deck XX Deck (30):
What are bence jones proteins?
Monoclonal light chains circulating in the serum or urine.
What is the most common mutation associated with primary hemochromatosis?
Mutation of the HFE protein which interacts with the transferrin receptor to increase endocytosis of the iron transferrin complex. This iron is added to the regulatory pool which controls expression of proteins involved in iron absorption.
What is the pathophysiology of iron deposition in hereditary hemochromatosis?
Mutated (inactivated) HFE proteins cause enterocytes and hepatocytes to detect falsely low iron levels which increases bodily iron accumulation through enterocyte increase of apical divalent metal transporter 1 (DMT1) which increases iron absorption from the intestinal lumen; and by hepatocyte decrease of hepcidin synthesis which causes increased ferroportin expression allowing for increased iron secretion into circulation.
What is the classic triad of symptoms in hereditary hemochromatosis?
Micronodular cirrhosis, diabetes mellitus, skin pigmentation.
For what conditions are patients with hereditary hemochromatosis at increased risk?
HCC, CHF, testicular atrophy/ hypogonadism.
What predisposes a patient on warfarin to warfarin-induced skin necrosis?
A protein C or protein S deficiency. This causes a relative hypercoaguable state with thrombotic occlusion of the microvasculature and skin necrosis due to rapid drop in protein C and factor VII levels.
Mutations to genes that code for epidermal growth factor receptors are associated with what cancers?
Non-small cell lung carcinoma (erbB1), breast cancer (erbB2 aka Her2/neu), some ovarian and gastric tumors
In what condition does a defective platelet derived growth factor play a role?
Chronic myelomonocytic leukemia
What is the mechanism of action of argatroban?
It is a direct thrombin inhibitor and binds directly tho the thrombin active site
Name the three direct thrombin inhibitors.
Hirudin, lepirudin, argatroban
What drugs are used to treat Heparin Induced Thrombocytopenia?
Direct thrombin inhibitors as they do not require antithrombin III for action.
What side effects are associated with Dapsone?
Fever, rash, methemoglobinemia, oxidative stress (hemolytic anemia in people with G6PD deficiency)
Name four triggers of G6PD deficiency anemia.
Infection, drugs (dapsone, antimalarials, sulfonamides, diabetic ketoacidosis, favism (fava beans).
When are bite cells most commonly seen?
Due to oxidant induced damage (i.e. in G6PD deficiency)
On crystal violet stain, how does G6PD deficiency present?
With Heinz bodies- small irregular, dark purple granules in RBCs. Peripheral smear will also show Bite cells (Caused by attempted removal by splenic monocyte macrophage system).
A prolonged PTT indicates a defect in what coagulation factors?
VIII, IX, XI, or XII.
Bleeding time is a measure of what?
In Hemophilia A and B, what do bleeding time labs show?
Isolated prolongation of PTT. PT, TT, and bleeding time are normal.
Deficiencies in what factors cause PT prolongation?
II, V, VII, X and fibrinogen.
What is the leading cause of blindness in developed countries?
Age related macular degeneration.
What is age related macular degeneration?
Degeneration of the central retina that presents as difficulty with driving, reading, watching TV, and other daily life activities. It can be classified as 'dry' or 'wet'.
What is dry age related macular degeneration?
Gradual loss of vision in one or both eyes due to subretinal drusen deposits or pigment changes. It usually progresses to wet AMD.
What is wet age related macular degeneration?
Abnormal blood vessels with subretinal fluid/ hemorrhage, gray subretinal membrane, neovascularization which lead to acute vision loss over a period of days to weeks. Caused by VEGF which causes retinal neovascularization.
How are dry and wet age related macular degeneration treated?
Dry and less advanced AMD: antioxidant vitamins and zinc; active and more-advanced wet AMD: anti VEGF inhibitors, laser therapy, phototherapy.
What type of oncogenic activity does Ras have?
What is Retinoblastoma (Rb) protein?
A regulator of the G1- S phase transition. It is active when it is hypophosphorylated (i.e. blocks transition to S phase)
What type of drug is raltegravir and what is its mechanism of action?
Integrase inhibitor in HIV which prevents the host cell from synthesizing HIV mRNA from DNA.
What type of protein is K-ras?
In a patient with folate deficiency anemia, what is seen on peripheral smear?
Pancytopenia and hypersegmented neutrophils.