Term
| What is the composition of blood? |
|
Definition
| Plasma 50-55%. RBCs 40-45%. White cells 1%. |
|
|
Term
Describe a typical RBC.
Describe a platelet. What are its 3 types of secretory granules? |
|
Definition
RBC: Biconcave disk, 6-9 microns in diameter. No nucleus. Central pallor 1/3 of diameter.
Platelet: 2-4 microns. Granules: Lysosomes, alpha-granules (PDGF-firbrosis, fibrinogen, vWF), delta-granules (ATP, ADP, Ca++ etc.) |
|
|
Term
What is Anisocytosis?
What is Poikilocytosis? |
|
Definition
Anisocytosis is variation in size.
Poikilocytosis is a variation in shape. |
|
|
Term
| What are the sequential sites of hematopoiesis? |
|
Definition
Yolk sac - up to 6 weeks GA nRBCs.
Aorta-gonad mesonephros
Placenta
Fetal liver - 6-24 weeks GA. Myeloid/Granulation appears.
Bone marrow - Non-nucleated RBCs, Granulocytes and Megakaryocytes are produced. |
|
|
Term
|
Definition
| It is a stem cell that is the common precursor for both vessels and hematopoietic cells. |
|
|
Term
| What are the two important niches for hematopoiesis? |
|
Definition
Vascular and Osteoblastic.
Osteoblastic: hypoxia - Hematopoietic stem cell quiescence.
Osteoblasts aid in homing via cytokines and quiescence via thrombopoietin, and osteopontin.
Vascular: Where active stem cells are. |
|
|
Term
| What are the 5 stages of hematopoiesis? |
|
Definition
1. Hematopoietic stem cell 2. Progenitor cell 3. Blast cell - recognizable 4. Intermediate cell 5. Mature cell
Note: It's a continuum. |
|
|
Term
| What are the phases of myeloid lineage? |
|
Definition
1. Myeloblast
2. Promyelocyte - lots of primary granules
3. Myelocyte - secondary granules
4. Metamyelocyte - notch in nucleus
5. Neutrophil |
|
|
Term
| What are the phases of erythroid lineage? |
|
Definition
1. Proerythroblast
2. Early/Intermediate erythroblast
3. Intermediate/late erythroblast
4. Orthochromic Erythroblast |
|
|
Term
| Where are neutrophils produced in the bone marrow? Erythroid cells? Megakayrocytes? |
|
Definition
| Neutrophils are more central. Erythroid are in islands that are more central. Megakaryocytes are near vessels, for easier release of platelets. |
|
|
Term
| How long do reticulocytes circulate? Neutrophils? Platelets? |
|
Definition
Reticulocytes (become erythrocytes) circulate 120 days.
Neutrophils circulate for hours then enter the tissues.
Platelets circulate 9-10 days (how long it takes to stop anti-platelet therapy). |
|
|
Term
| What is a Howell-Jolley body? |
|
Definition
| They are peices of nuclei that haven't been removed properly from RBCs. |
|
|
Term
| What are the granules contained in platelets? What are their functions? |
|
Definition
Alpha granules: (contain proteins including vWF and p selection) promote platelet recruitment and aggregation, blood clotting activation and eventual wound healing.
Dense (delta) granules: (contain smaller molecules including ADP) Help the platelet recruit more platelets to the thrombus. |
|
|
Term
| What is the surface connected canalicular system? |
|
Definition
| It is a modification of the ER which provides for easy release of granules and provides excess membrane for shape change. |
|
|
Term
| What anti-platelet factors are released by healthy endothelium? |
|
Definition
NO: Nitric oxide
PGI2: Prostacycline - inhibits platelet activation
Ecto-ADPase (CD-39): Breaks down ADP (an important platelet agonist). |
|
|
Term
| What are the phases of platelet activation? |
|
Definition
1. Adhesion - binding tot eh subendothelial matrix
2. Activation - change from quiescent state to promote hemostasis
3. Secretion - release of granule contents
4. Aggregation - binding to other platelets through active GPIIb/IIIa (Fibrinogen/vWF aggregation). |
|
|
Term
| Describe the adhesion step of platelet activation. |
|
Definition
| First vessel injury exposes vWF and collagen. Second the damaged endothelium releases thrombin (activates the clotting cascade and platelet activation) and endothelin (vasoconstriction), and decreases production of ecto-ADPase. Platelets adhere to the collagen and vWF and are activated. |
|
|
Term
| Describe the activation and secretion step of platelet activation. |
|
Definition
| Platelet agonists include ADP, thromboxane A2, collagen, thrombin and epinephrine. These are released when endothelium damage occurs. Activation leads to shape change, thromboxane A2 release, granule release, active GPIIb/IIIa receptor expression, |
|
|
Term
| Describe the aggregation step of platelet activation. |
|
Definition
| Aggregation is mediated by the activated GP IIb/IIIa receptor. When activated it can signal in two directions - when it binds fibrinogen it activates the platelet. When it's expressed, it activates other platelets. Fibrinogen mainly (and vWF, etc minorly) serves as the bridge to bind platelets together. |
|
|
Term
|
Definition
| Thromboxane A2 is produced by activated platelets. It is a potent platelet agonist. Aspirin inhibits its production by acetylating cyclooxygenase - an enzyme needed in the production process. |
|
|
Term
| How does phospholipid distribution relate to platelet activation? |
|
Definition
| Under normal (resting) conditions, the platelet keeps negative phospholipids on the interior leaflet of the bilayer. Upon activation, those are presented on the exterior providing a surface for the Vitamin K factors to bind and concentrate their activity. |
|
|
Term
| What are some common tests of platelet function? |
|
Definition
PFA-100 (platelet function analyser)
Light transmission aggregometry - shine light, add agonists and see how much it clears. |
|
|
Term
| What are common acquired platelet function defects? |
|
Definition
| 1. Drugs (NSAIDs) 2. Uremia (metabolic byproducts inhibit platelet function) 3. Dysproteinemia 4. Myeloproliferative disorders 5. Cardiopulmonary bypass (artificial surfaces cause platelet activation and exhaustion) 6. Antiplatelet antibodies mess w/ platelet receptors. |
|
|
Term
| Describe the role of platelets in atherosclerosis. |
|
Definition
| Platelets stimulate inflammation in endothelial cells through CD40L and bind w/ monocytes through p-selectin. Circumstantial evidence connects platelets and atherosclerosis - primarily platelet factors are present in lesions, and antiplatelet drugs reduce the risk of ischemic events and death. |
|
|
Term
| What are 4 strategies for platelet inhibition? |
|
Definition
1. Inhibit P2Y12 ADP receptor activation - clopidogrel, etc
2. Inhibit TxA2 synthesis and secretion - Aspirin (ASA)
3. Increase platelet cAMP levels - Dipyridamole
4. Inhibit GpIIa/IIIb receptors - abciximab |
|
|
Term
| What is primary hemostasis? Secondary hemostasis? |
|
Definition
Primary: Vasoconstriction and formation of the platelet plug
Secondary: Fibrin formation |
|
|
Term
| What are microparticles and how do they participate in hemostasis? |
|
Definition
| Microparticles are released when tissue injury occurs. They carry tissue factor. TF stimulates the cascade to from the fibrin clot by binding with factor VIIa (the only factor that's not a zymogen). |
|
|
Term
|
Definition
|
|
Term
| The key of the clotting cascade is the conversion of fibrinogen (factor I) to fibrin. What is required to make this happen? |
|
Definition
| Fibrinogen is converted to fibrin by thrombin. Thrombin is converted from prothrombin (factor II) in the presence of calcium (factor 4) and tissue thromboplastin (factor 3) by factor Xa. |
|
|
Term
| What is the importance of factor XIII? |
|
Definition
| It cross links the fibrin clot to make it strong. A deficiency here could lead to significant delayed bleeding. |
|
|
Term
| Thrombin, when created activates the intrinsic pathway. Describe that pathway. Why is it important? |
|
Definition
Thrombin activates factor V, factor VIII (absent in hemophiliacs) and factor XI. Factor VIIIa and factor IXa (produced by XIa) increase the production of Xa 10,000x. Factor Va increases thrombin production by 10,000x. They are important cofactors.
Without this pathway, sufficient thrombin couldn't be generated, since the extrinsic pathway only generates trace amounts of thrombin. |
|
|
Term
| Which factors are Vitamin K dependent? |
|
Definition
| II, VII, IX, and X are vitamin K dependent. Warfarin works on this. These can bind to the negative phospholipids on activated platelets. |
|
|
Term
| What factors are not important for in vivo clot formation? |
|
Definition
Factor XII is only important in vitro, because in vivo thrombin activates factor XI.
Factor XI deficiency is only associated with minor bleeding because factor IX is activated by TF-VIIa. |
|
|
Term
What are two tests to evaluate the cascade?
What does thrombin time evaluate? |
|
Definition
Prothrombin time (PT/INR): Evaluates the integrity of the extrinsic pathway.
activated Partial Thromboplastin Time (aPTT): Evaluates the integrity of the intrinsic pathway.
Note: Activity needs to be quite reduced (to <30-40%) for these to come up abnormal.
Thrombin time evaluates the conversion of fibrinogen to fibrin. Looks for abnormal structure there. |
|
|
Term
| Intact endothelium prevents coagulation by generating quite a few factors. Name some. |
|
Definition
| Nitric Oxide, Prostacyclin (PGI2), CD66(ectoADPase) are discussed w/platelets. ADAMTS13 cleaves vWF. Tissue Factor pathway inhibitor (TFPI) binds TF-VIIa-Xa complex. Thrombomodulin (TM) binds thrombin. Proteoglycans activate antithrombin (AT) which is a thrombin inhibitor and blocks Xa activity. |
|
|
Term
| What are proteins C and S? Protein Z? |
|
Definition
They are physiologic anticoagulants. S is a cofactor for C which inactivates factors Va and VIIIa. C is activated by thrombin-thrombomodulin.
Protein Z inhibits factor Xa. |
|
|
Term
| What factors participate in fibrinolysis? |
|
Definition
| Endothelial cells produce tissue plasminogen activator (tPA) which activates plasminogen to plasmin which in turn leads to fibrin degradation. |
|
|
Term
| What are the 4 classes of therapeutic anticoagulants? |
|
Definition
1. Vitamin K antagonists - warfarin
2. Heparins - Unfractionated & low molecular weight
3. Direct Xa Inhibitors - Pentasaccharide, Rivaroxiban, Apixaban
4. Direct Thrombin inhibitors - Hirudins, Argatroban, Dabigatran |
|
|
Term
What is warfarin's mechanism of action?
How is it metabolized?
How do polymorphisms affect its dosage?
How long does it take to kick in? |
|
Definition
It prevents vitamin K from being reduced. The reduced form is required for carboxylation of clotting factors (which activates them). VKOR1 is the important enzyme in carboxylation.
It is metabolized by the CYP 2C9 pathway.
Polymorphisms in the CYPs and VKOR lead to different dosage requirements. Dose required decreases w/age.
5 days are required for the full effect. |
|
|
Term
What is the INR?
What is a target for most patients? |
|
Definition
International Normalized Ratio. It is derived from PT. Makes results from different labs comparable.
INR = (ptPT/controlPT)^ISI
ISI: international sensitivity index (specific to reagent used).
Goal INR is normally 2-3. |
|
|
Term
What are some side effects of warfarin?
How do you treat a patient with an elevated INR? |
|
Definition
Increased risk of bleeding w/ drug interactions, liver disease, etc. Teratogenic. Warfarin necrosis - due to low protein c/s (natural anticoagulants).
Treat high INR w/ vitamin K (oral or IV). Fresh frozen plasma also helps. |
|
|
Term
What is the mechanism of action for Heparin?
How do you monitor treatment? |
|
Definition
It is a large GAG. Has a sequence that binds to antithrombin (AT). This complex inhibits thrombin and factor Xa. Works immediately. Heparin is inactivated if given orally.
Treatment must be carefully monitored w/ aPTT since half-life is variable. Heparin can be counteracted w/protamine. |
|
|
Term
| What are some side effects of unfractionated heparin? |
|
Definition
Bleeding, most commonly in elderly/underweight patients.
Thrombocytopenia: rare but important - antibodies agglutinating platelets.
Osteoporosis.
Mild inhibition of aldosterone, increasing potassium. |
|
|
Term
| How does LMWH differ from unfractionated Heparin? |
|
Definition
| It binds AT, and is anti Xa, but has little antithrombin activity. It has a lower bleeding rate, better bioavailability, and more predictable effects. No monitoring required. Subcutaneous injection. Protamine has a smaller effect on LMWH. |
|
|
Term
| What is the mechanism of Fondaparinux (Factor Xa inhibitor)? |
|
Definition
| Fondaparinux is a pentasacharide. It binds to AT and changes it's conformation inactivating Xa like LMWH. Long half-life, once daily injections. Contraindicated in renal failure, and low body weight. |
|
|
Term
Why are Direct Anti-Xa inhibitors important?
Why are Direct Thrombin Inhibitors important?
What are their drawbacks? |
|
Definition
They are oral & don't require binding to AT.
DTIs are derived from leeches. They bind to and inhibit the action of thrombin. IV and oral forms exist. *They inactivate bound and unbound thrombin and don't require AT.
Drawbacks: No antidote. No method of monitoring. |
|
|
Term
Where does atherosclerosis begin?
Describe the process. |
|
Definition
It begins in areas of turbulent flow. It is a subintimal lesion.
Arteries respond to injury by recruiting Monocytes which releasing cytokines. Smooth muscle cells migrate from the media to the intima. They proliferate collagen. Nutrition can't occur (too thick) leading to necrosis and an inflammatory response. Proliferation continues with a fibrous cap covering everything. |
|
|
Term
| What are the steps of atherogenesis (a chronic inflammatory disease)? |
|
Definition
1. Fatty streak formation (contain foam cells). Can resolve.
2. Fibrous plaque formation
3. Calcification: "Hardening of the arteries." |
|
|
Term
| What are some complications of atherosclerosis? |
|
Definition
1. Calcification (hardening of arteries)
2. Plaque fissuring/rupture (often due to inflammatory cell accumulation at the site of rupture)
3. Atheroembolism
4. Aneurism formation |
|
|
Term
| Normally high LDL levels in a cell lead to down regulation (homeostasis). Why is LDL a problem then? |
|
Definition
Macrophages take up modified LDL (scavenger receptors) & are not down-regulated.
Note: anything that can cause inflammation it the endothelium can lead to atherosclerosis. |
|
|
Term
| What is the mechanism of action for Statins? |
|
Definition
| They are HMGCoA-reductase (important in cholesterol synthesis) inhibitors. They lower serum cholesterol, but also inhibit the inflammation having a larger than expected effect. |
|
|
Term
| What is C reactive protein (CRP)? |
|
Definition
| It is a marker for systemic inflammation and is associated w/ MI and atherosclerotic lesions. It allows uptake of unmodified LDL. |
|
|
Term
| What do Lupus (SLE) and Rheumatoid arthritis have to do with atherosclerosis? |
|
Definition
| They are autoimmune disorders. Individuals with them have a much higher incidence of atherosclerosis. This provides more evidence that atherosclerosis is linked to chronic inflammation. |
|
|
Term
What is the normal weight of the heart?
Sudden cardiac death accounts for what percentage of all cardiac deaths? |
|
Definition
0.5% of total body weight.
50%. Up to 80% due to atherosclerosis. |
|
|
Term
| When does cell death start to occur in ischemia? |
|
Definition
| After 20-40 minutes. That's why it is so urgent to get them to the cath lab. |
|
|
Term
| What are the risk factors for ischemic heart disease? |
|
Definition
Haslipids
Heredity Age Sex (M>F) Lipidemia Increased weight (obesity) Pressure (hypertension) Inactivity Diabetes Smoking. |
|
|
Term
| What are the changes that occur with MI? How long for each? |
|
Definition
1-4 hrs: Wavy fiber change.
4-24 hrs: Pale, swelling - coagulation necrosis. PMNs
3-5 days: Mottled, yellow/red. Heavy PMNs
5-7 days: Mottled, macrophages/fibroblasts.
2-4 weeks: Granulation tissue
5-8 weeks: Scarring |
|
|
Term
| What are 5 things that can lead to acute MI? |
|
Definition
1. Stenosing atherosclerosis of the coronary arteries.
2. Intraluminal thrombus (plaque rupture)
3. Coronary vasospasm
4. Nonatherogenic coronary disease (trauma, vasculitis, etc.)
5. Hemodynamic derangements. |
|
|
Term
| What types of lesions cause the most MIs? |
|
Definition
| Lipid rich, soft plaques. The more advanced hardened (with collagen) ones are more important in ischemia. This is due to the fact that the soft ones are more prone to rupture causing an infarct. |
|
|
Term
| What are some complication of the treatments we give to correct CAD? |
|
Definition
1. Angioplasty causes tearing and can lead to dissection.
2. Stents are thrombogenic and can cause occlusion.
3. Vein grafts undergo arterialization (and can undergo atherosclerosis). |
|
|
Term
| What is "positive remodeling"? |
|
Definition
| It is the idea that atherosclerotic plaques grow away from the lumen so lumen occlusion usually doesn't occur until the process is quite advanced. |
|
|
Term
| What is the biggest determinant of myocardial oxygen demand? |
|
Definition
| LV wall tension (determined by ventricular volume and systolic pressure). |
|
|
Term
| What changes occur within the heart during ischemia? |
|
Definition
1. Abnormalities in regional diastolic relaxation occur within seconds.
2. Regional systolic dysfunction follows.
3. Filling changes occur.
4. EKG changes are seen (ST depression/elevation).
5. Angina is felt. Note: 1/2 of pts w/angina experience asymptomatic episodes as well. |
|
|
Term
| What is microvascular coronary disease? |
|
Definition
| There is abnormal flow reserve despite the lack of a significant stenosis. |
|
|
Term
|
Definition
Pain/discomfort in the chest or adjacent areas caused by insufficient blood flow to the heart.
May present atypically especially in women, elderly and diabetics (dyspnea, nausea, fatigue, faintness). |
|
|
Term
| What are your treatment options for CAD? |
|
Definition
1. Non-pharmacologic therapies - exercise/lifestyle modification.
2. Pharmacologic therapies
3. Risk factor modification
4. Revascularization |
|
|
Term
| What are the ABCs of the treatment of stable angina? |
|
Definition
Aspirin and anti-anginal therapy
Beta-blocker and BP
Cigarette smoking and cholesterol
Diet and diabetes
Education |
|
|
Term
| What are the goals of treatment in CAD? |
|
Definition
1. Relieve symptoms (improve quality of life).
2. Prevent MI and death (increase duration of life).
Treat risk factors, treat to prevent symptoms, low threshold for ischemia or LV dysfunction - revascularization. |
|
|
Term
| What are acute coronary syndromes (ACS)? |
|
Definition
They respresent the continuum of unstable angina, to NSTEMI (partial occlusion), to STEMI (complete occlusion).
Hallmark: Symptoms occur without provocation. |
|
|
Term
| How do fibrinolytics work? |
|
Definition
| They activated plasminogen which is converted to plasmin which breaks down fibrin. |
|
|
Term
| What are the 5 classifications of MIs? |
|
Definition
1. Due to a primary event, i.e. plaque rupture
2. Due to supply-demand imbalance, i.e. vasospasm, hypotension, hypertension, embolism, etc.
3. Sudden cardiac death - no reliable biomarkers
4a. Associated w/ PCI
4b. Associated w/ in-stent thrombosis
5. Associated by CABG surgery. |
|
|
Term
|
Definition
1. Restore blood flow ASAP (fibrinolysis or catheterization)
2. Stop clot formation (anticoagulation & antiplatelet)
3. Relieve pain
4. Reduce ischemia (beta-blockers)
5. Control spasm (nitrates) |
|
|
Term
| When should GP IIa/IIIb inhibitors be used? |
|
Definition
| They best used with +troponins, and/or in the setting of PCI (percutaneous coronary intervention). |
|
|
Term
| What is the optimal strategy to treat UA/NSTEMI? |
|
Definition
| The evidence favors an early invasive approach. |
|
|
Term
| What medications should ACS patients leave the hospital with? |
|
Definition
| Antiplatelets, beta blocker, ACE-I, Statin, instructions to stop smoking and increase activity. |
|
|
Term
What are the 4 different kinds of lipids we discussed?
What are they used for? |
|
Definition
1. Cholesterol: a steroid w/ a hydrophilic end 2. Free fatty acids: diffusable & used for fuel (omega-3s have a double bond 3 carbons away from the omega tail) 3. Triglycerides 4. Phospholipids
They are used as cell membranes, fuels, and precursors. |
|
|
Term
| Where is cholesterol important in the body? |
|
Definition
| It is used in bile salts to help break down fat. |
|
|
Term
What is the structure of a typical lipoprotein?
What is their purpose? |
|
Definition
It has an amphipathic surface made up of phospholipids and apolipoproteins (cofactors for enzymes and receptors as well as structural scaffolds), and a hydrophobic core made up of cholesterol esters and triglycerides.
They deliver fats as fuel, and aid in cholesterol and phospholipid transport, |
|
|
Term
What are the various lipoprotiens in size order?
How else are they classified?
What is their trajectory (i.e. how do they go from one to the other)? |
|
Definition
HDL3, HDL2, LDL, IDL (intermediate), VLDL, Chylomicron.
They are also classified by electrophoresis (Beta-LDL, PreB-VLDL, alpha-HDL)
Chylomicrons are broken down to LDL.
HDL follows it's own pathway of production with HDL2 being the final product. |
|
|
Term
| What are the 4 pathways of lipoprotein transport? |
|
Definition
1. Exogenous pathway (taken up from outside the body)
2. Endogenous pathway (made by the liver)
3. Reverse cholesterol transport (HDL takes up cholesterol from the periphery)
4. Enterohepatic circulation (bile salts circulate from the liver to the gut back to the liver) |
|
|
Term
| What are the 3 key lipoprotein transport enzymes? |
|
Definition
1. Lipoprotein lipase (LPL): breaks down triglycerides to FFAs
2. Lecithin-cholesterol transferase (LCT): adds lipids to HDL
3. Cholesterol ester transfer protein (CETP): Moves cholesterol from HDL to LDL |
|
|
Term
| Describe the exogenous pathway of lipoprotein transport. |
|
Definition
| Enterocytes take up and package triglycerides, cholesterol, phospholipids, ApoA, & ApoB48 and send them off into the subclavian vein. These nascent chylomicrons mature to chylomicrons by picking up Apo C & E from HDL. ApoC interacts with LPL & triglycerides are broken down into FFAs. The chylomicron remnant is taken up by the liver (using LRP) to be recycled. |
|
|
Term
| Describe the endogenous pathway of lipoprotein transport. |
|
Definition
The liver packages lipids into nascent VLDL (ApoB100 is important here). These are processed by HDL (get Apo C & E) to become VLDL. Apo C interacts w/LPL to turn triglycerides into FFAs. VLDL becomes IDL. IDL is further processed by HDL until it only has ApoB100 and becomes LDL. This us taken up by the liver (LDLR) or by peripheral cells.
*Note: modified (oxidized) LDL is taken up by scavenger receptors rather than LDLR overloading macrophages. |
|
|
Term
| Describe reverse cholesterol transport. |
|
Definition
| Hepatocytes/enterocytes convert Apo-A1 to preB HDL to HDL3. HDL3 is converted to HDL2 by interaction with chylomicrons and VLDL. LCAT (activated by ApoA1) forms cholesterol ester which is carried in HDL (uptake). Cholesterol is then transported to the liver via SR-B1 (a scavenger receptor) or to LDL via CETP and then to the liver via LDLR. |
|
|
Term
| Describe enterohepatic circulation. |
|
Definition
| Bile salts break down fats, then 95% are re-absorped. Occurs 6-10 times a day. |
|
|
Term
What causes familial hypercholesterolemia?
What are some signs? |
|
Definition
An autosomal dominant mutation in LDLR. (Liver uptake of cholesterol inhibits cholesterol synthesis).
Signs: Xanthomas (tendinous/eyelid), arcus corneae, premature atherosclerosis. |
|
|
Term
| What is important about PCSK9 mutations? |
|
Definition
| This functions in LDLR degradation. If it malfunctions, there are more LDLRs and less LDL circulating. |
|
|
Term
What are the four main treatments for elevated cholesterol levels?
How do they work? |
|
Definition
1. Statins: Competitively inhibit HMGCoA reductase (endogenous pathway)
2. Niacin: Inhibits hormone sensitive lipase (converts TG to FFAs). This lowers TG production. Can be added to statins.
3. Fibrates: Best drug for lowering TG.
4. Bile Acid sequestrants: Bind bile acids preventing reuptake. They are a good addition to statins. Side effect: constapation. |
|
|
Term
What happens when you increase the dose of statins?
What statin should you put them on to reduce interactions?
What is the primary side effect of statins? |
|
Definition
Doubling the dose of a statin only drops LDL 6% more. The big hit is first.
Pravastatin is not metabolized by the CYP450 system.
The primary side effect is myalgia (lower extremity, get worse w/time). Liver toxicity (check bilirubin). Insulin resistance. Confusion (anecdotal). |
|
|
Term
| What do you do to treat statin toxicity? |
|
Definition
| If mild symptoms try another. Or reduce to symptom free dose and add adjunct therapy. |
|
|
Term
| What are the benefits and side effects of niacin (nicotinic acid)? |
|
Definition
Best at raising HDL. Lowers triglycerides. Moderate lowering affect on LDL. Only drug that lowers Lp(a).
Side effects: Flushing, hyperglycemia, hyperuricemia, liver.
Contraindications: Liver disease, severe gout, peptic ulcer.
Note: Risk reduction is much better w/statins (don't fall in love with the lipid profile. They key is risk reduction). |
|
|
Term
| What are the benefits and side effects of fibrates? |
|
Definition
Significantly lower TG. Can raise or lower LDL (depending on TG levels). Raise HDL (if low).
Side effects: dyspepsia, gallstones, myopathy.
Contraindications: Severe renal/hepatic disease.
They have been shown to reduce coronary events. |
|
|
Term
| What are the effects of Beta-blockers? |
|
Definition
Decrease HR, lower BP, decrease contractility (usually negligible). CO generally stays the same or rises due to the drop in BP.
End: _lol |
|
|
Term
| What are the effects of nitrates? |
|
Definition
| Vasodilation leading to decreased BP and decreased venous return (Reduce pre-load and afterload). It also dilates the coronary arteries increasing coronary blood flow. |
|
|
Term
| What are the effects of calcium channel blockers? |
|
Definition
They lower HR (dihydropyradines may increase it), lower BP, decrease contractility, and increase coronary flow.
Dihydropyradines are the most potent vasodilators. Non-dihydropyradines are more potent HR reducers.
Eg: Amlodapine (a dihydropyradine), Diltiazem, Verapamil |
|
|
Term
| What is Ranolazine? How does it work? |
|
Definition
Ranolazine can improve symptoms of ischemia by decreasing ATP usage, increasing contractility and relaxation of the myocardium, and decreasing arrhythmias.
It closes the late Na+ gate which tends to stay open too long in ischemia. This protects from the Ca overload that occurs when the gate opens.
Key: it doesn't cause any changes in HR, BP or coronary flow and is therefore a good additive agent. |
|
|
Term
| What are the effects of ACE Inhibitors? |
|
Definition
They lower the production of angiotensin II one of the most potent vasoconstrictors in the body. They
Side effects: cough, skin reactions, renal dysfunction (but late effects protect the kidney).
End: _pril. |
|
|
Term
| What are the effects of angiotensin receptor blockers (ARBs)? |
|
Definition
Similar but less potent effects to ACE Inhibitors. Very infrequent side effects.
End: _artan |
|
|
Term
| What are the causes of acquired valvular stenosis? |
|
Definition
1. Post-inflamatory (rheumatic) mitral or aortic stenosis.
2. Calcification aortic stenosis. |
|
|
Term
| What are the causes of acquired valvular incompetence? |
|
Definition
1. Leaflet abnormality (rheumatic, infective endocarditis)
2. Papillary muscle damage (ischemia leading to mitral valve disease)
3. Valve ring abnormalities (syphilitic aortitis, mitral ring dilation w/cardiac dilation in HF). You will see widening of the commissures. |
|
|
Term
| What is the sinus of Valsalva? |
|
Definition
| It is the area behind the valve flap. It can be filled w/calcified lesions to prevent opening. |
|
|
Term
| What are the different types of endocarditis (the primary process leading to valvular disease)? |
|
Definition
1. Nonbacterial thrombotic endocarditis
2. Rheumatic endocarditis
3. Libman-Sacks endocarditis (lupus)
4. Infective endocarditis |
|
|
Term
| What is nonbacterial thrombotic endocarditis? |
|
Definition
| It is the deposition of small masses (fibrin, platelets, etc) on cardiac valve leaflets (leaflets themselves are not harmed). Valves are usually previously normal. Related to hypercoaguable states (malignancies). Can embolize. |
|
|
Term
| What is infective endocarditis? |
|
Definition
Infection of valves/endocaridum w/formation of a vegetation (mass of thrombotic debris & organism). Can be acute (staph. aureus) or sub acute (alpha hemolytic strep). Leads to destruction of the valve leaflets/chordae/papillaries. Can lead to embolization/infarcts.
Risk factors: IV drug use, prosthetic valves. |
|
|
Term
How do you diagnose acute rheumatic fever?
What are the Jones criteria? |
|
Definition
Evidence of a streptococcal infection.
Joints
O-Heart
Nodules (aschoff nodules - last for >40 yrs)
Erethema marginatum
Syndeham Chorea |
|
|
Term
| What are the effects of rheumatic endocarditis on the heart? |
|
Definition
Inflammation and edema most commonly of the mitral then aortic valve.
They will look thickened and irregular in shape with stenosis and possible regurgitation. |
|
|
Term
|
Definition
| It is a thickening/fibrosis of the endocardium due to a regurgitant jet of blood. It can serve as a nidus for infection. |
|
|
Term
| What are the causes, effects, diagnosis, and treatment of mitral stenosis? |
|
Definition
Causes: Rheumatic
Effects: Elevated LA pressure - pulmonary congestion/hypertension - RV dysfunction - systemic congestion. Low CO. LA dilation - Afib - embolism.
Diagnosis: Opening snap, diastolic rumble.
Treatment: Diuretics, beta blockers. Balloon valvotomy, or surgical commissurotomy. |
|
|
Term
| What are the causes, effects, diagnosis, and treatment of aortic stenosis? |
|
Definition
Causes: Bicuspid valves, degenerative (calcific), rheumatic
Effects: LV hypertrophy - LV diastolic dysfunction - LV systolic dysfunction. Ischemia due to higher demand. Low CO.
Diagnosis: Dyspnea, angina, (pre)syncope. Midsystolic murmur, fourth heart sound
Treatment: Surgery when symptoms develop. Generally open. |
|
|
Term
| What are the trade-offs in recommending a mechanical vs. a biosynthetic (from pig or cow) valve replacement? |
|
Definition
| Mechanical lead to clot formation, biosynthetic can wear out. |
|
|
Term
| What are the causes, effects, diagnosis, and treatment of aortic regurgitation? |
|
Definition
Causes: Congenital (bicuspid valves), Degenerative (calcific), rheumatic, things that dilate the aorta.
Effects: Increased preload & afterload (has to pump more blood to compensate for what will come back). Leads to dilation and hypertrophy of the LV.
Diagnosis: Dyspnea, angina, displaced LV impulse, brisk upstrokes w/rapid fall-off (wide pulse pressure), S3, decrescendo diastolic blowing murmur, systolic murmur (due to massive flow). Can also mimic mitral stenosis since the jet can hit the mitral leaflet impeding opening.
Treatment: Ultimately surgical replacement (onset of symptoms, LV systolic dysfunction, or severe LV dilation). |
|
|
Term
What is concentric hypertrophy?
What is eccentric remodeling?
What is eccentric hypertrophy? |
|
Definition
Concentric hypertrophy is thickening of the ventricular wall without an increase in volume.
Eccentric remodeling is an increase in volume without an increase in wall thickness.
Eccentric hypertrophy is an increase in volume and wall thickness and is what you would see in aortic regurg. |
|
|
Term
| What are the causes, effects, diagnosis, and treatment of mitral regurgitation? |
|
Definition
Causes: Valve prolapse (congenital), degenerative, anything that will cause problems with the mitral machinery.
Effects: Volume overload of LV & LA (dilation). Can lead to pulmonary and systemic congestion (fluid keeps backing up).
Diagnosis: Dyspnea, angina, fatigue, palpitations (Afib), S3, brisk carotid upstrokes, holosystolic murmur, diastolic rumble (severe).
Treatment: Watch for endocarditis (more common in this pop), don't wait for severe symptoms before surgery - watch for systolic dysfunction, pulmonary hypertension, afib. Low threshold for surgery (generally a repair, not a replacement). |
|
|
Term
What happens to pulmonary resistance after birth?
What does this mean for shunts?
What are the effects on the lungs?
What symptoms might you see? |
|
Definition
Before birth pulmonary resistance is high. As PaO2 goes up this resistance will drop.
This means that connections between left and right circuits will lead to left to right shunting. If there's normal CO, there is too much circulation in the lungs. This leads to stiff lungs and increase work of breathing.
Symptoms: Failure to thrive. Difficulty feeding (hardest work and infant does). |
|
|
Term
| What is Eisenmenger's Syndrome? |
|
Definition
| Eisenmenger's is cyanosis due to a reversal of flow through a VSD. This occurs because of increased pulmonary resistance that surpasses systemic resistance. Happens most often when pulmonary gets increased flow & increased pressure. |
|
|
Term
How do you assess the degree of shunting?
What is the equation? |
|
Definition
Through saturations (not pressures). Look at O2 saturations in the pulmonary artery vs systemic venous saturations (70%).
Qs=O2 delivery/(change in O2 saturation)
Qp=O2 uptake/(change in O2 saturation)
O2 delivery=O2 uptake :: Qs/Qp=(SA-SV)/(PV-PA)
Qp/Qs tells us about the degree of shunting. Large shunts 2-3:1. (Q=flow) |
|
|
Term
| What happens if you close an Eisenmenger's shunt? |
|
Definition
| Disaster! The RV can't push against the resistance, and with the decreased preload output drops. Can lead to syncope and RV failure. Pulmonary vasodilators help deal with this concern. |
|
|
Term
| How do you calculate pulmonary vascular resistance (to see if it's safe to close a shunt)? |
|
Definition
You use the Q=∂P*R equation. R=Q/∂P
Pulmonary Vascular resistance is measured in Wood units. Normal is <2. If >6-8 closure is unsafe. |
|
|
Term
What is a CAVC?
What about a partial anomalous pulmonary venous connection (PAPVR)? |
|
Definition
It is a complete AV canal. A shunt connecting all 4 chambers of the heart.
PAPVR: some pulmonary veins drain to the RA instead of the LA. Works like an atrial septal defect. |
|
|
Term
What is an AP window?
What is a PDA? |
|
Definition
It is an aortopulmonary window, i.e. a connection between the aorta and the pulmonary trunk.
PDA is a patent ductus arteriosus (more common in premies). |
|
|
Term
| What are the effects of any left to right shunt? |
|
Definition
| All left to right shunts lead to similar effects. Pulmonary overcirculation (congestion), pulmonary vascular disease, extra work for one of the ventricles (determined by the location of the shunt - before the tricuspid valve: RV, after (including VSD): LV) leading to diastolic then systolic dysfunction. Arrhythmias can also develop in the "overworked" myocardium. |
|
|
Term
| When should you send an infant for surgery on a VSD? |
|
Definition
1. If the pulmonary congestion causes failure to thrive.
2. If the defect exposes the pulmonary circuit to high flow at high pressures.
3. If the ventricle is dilating and therefore at risk for failure. |
|
|
Term
What is prostaglandin E used for?
Why is this important? |
|
Definition
It allows a PDA to be maintained.
This allows for collateral flow when problematic defects are present. This development allows for hemodynamic stability to be maintained and surgery to be delayed for many lesions. |
|
|
Term
| What are the 3 basic mechanisms of cyanosis? |
|
Definition
1. Reversed connections: e.g. transposition of the great arteries. Key to survival is maintaining communication of the 2 parallel circuits (PDA & PFO).
2. Absent connections leading to complete mixing of systemic and pulmonary venous blood. O2 stats can be preserved if lungs are over circulated. E.g. tricuspid atresia (RA/RV don't connect).
3. Shunt w/ and inadequate right heart pump. E.g. Teratology of Fallot. Leads to right to left shunting. |
|
|
Term
What happens in hypoplastic left heart syndrome?
What is needed for development of pathways? |
|
Definition
Left heart doesn't develop fully. Pulmonary venous return crosses PFO to RA. Systemic circulation is provided by PDA. This is a ductal dependent lesion.
Remember flow is vital for development. If you can return flow soon enough, you may rescue development. |
|
|
Term
|
Definition
| Total anomalous pulmonary venous return. The pulmonary veins don't connect to the LA, rather it drains through systemic veins to the RA. Complete mixing leads to cyanosis. PFO is vital to maintain circulation to the systemic circuit. |
|
|
Term
| What are the elements of the Teratology of Fallot? |
|
Definition
1. Ventricular septal defect.
2. Pulmonary stenosis.
3. Overriding aorta.
4. Right ventricular hypertrophy.
Squatting on exertion is the classic presentation. |
|
|
Term
| What is Ebstein's anomaly? |
|
Definition
| It is severe tricuspid regurgitation. RA pressure exceeds LA pressure leading to right to left shunting. PDA is necessary to maintain pulmonary perfusion. As pulmonary arterial pressure drops the PDA may no longer be necessary. |
|
|
Term
| What are 3 causes of congenital pump failure? |
|
Definition
1. Obstruction to flow (stenosis).
2. Severely leaky valves.
3. Myocardial failure (congenital problem w/myocardium or the blood supply). |
|
|
Term
| What is the likely cause of shock in the first two weeks of life? |
|
Definition
| Closure of the PDA in a ductal dependent lesion. The duct usually closes at about 2 weeks. |
|
|
Term
| What are adult complications of congenital heart defects? |
|
Definition
| Valvular problems (jet lesions, dilation of the annulus). Aneurismal dilation (as a primary problem, or secondary to a repair). |
|
|
Term
| What are adult complications of cyanosis? |
|
Definition
| Erythrocytosis & hyperviscosity. If it becomes chronic (uncommon in this country): Cerebral abscess (especially w/R to L shunts - lung acts as a filter). Renal dysfunction. Gout. |
|
|
Term
| How much does the size of a vessel need to be reduced in order for symptoms to develop? |
|
Definition
| It must be reduced markedly (~85%) in order for there to be enough of an effect for symptom development. |
|
|
Term
| What happens in the osteum primum type atrial septal defect? |
|
Definition
| It is a defect in the endocardial cushion formation. It leads to an ASD, but also a defective (clefted) Mitral valve. |
|
|
Term
What is the most common type of VSD?
Which are louder small or large defects?
Which have a greater effect on the heart? |
|
Definition
In the part membranous part muscular area of the IV septum. This junction (or any junction) is an area of weakness.
Small defects are louder.
Large defects have a bigger effect on the economy of the heart. |
|
|
Term
| What happens to the heart in a VSD? |
|
Definition
If it is only membranous it affects the left ventricle.
If it is part membranous part muscular it can lead to dilation and hypertrophy of both sides of the heart. (different lectures said different things, I'm trying to makes sense of it here). |
|
|
Term
| What is the effect of a PDA on the heart? |
|
Definition
| Both sides of the heart hypertrophy and dilate. (de Frietas lecture said only the left side would be affected) |
|
|
Term
| The pulmonary vasculature can expand. How far past normal can it go before pulmonary hypertension develops? |
|
Definition
| It can expand 2-3x normal, but after that hypertension develops. Permanent increases in resistance can occur if nothing is done. |
|
|
Term
| What happens to the heart in cases of severe stenosis? |
|
Definition
| Pressure hypertrophy of the area trying to pump through the stenotic area. Can lead to myocardium failure. |
|
|
Term
What is coarctation of the aorta?
What does it cause? |
|
Definition
It is a narrowing of the aorta in the area between the left subclavian artery and the ductus arteriosus.
This leads to LV hypertrophy and huge pressures in the ascending aorta that can lead to rupture. |
|
|
Term
| What is fetal coarctation? |
|
Definition
| It is hypoplastic left heart syndrome. A ductal dependent lesion. |
|
|
Term
| Where do you find a VSD in the shape of a U? |
|
Definition
| In the teratology of fallot. This disease has low mortality considering all that's going on. Surgery is quite successful. |
|
|
Term
| What is the difference between volume hypertrophy and pressure hypertrophy? |
|
Definition
| Volume hypertrophy occurs when a chamber contracts against increased volume load. Pressure hypertrophy occurs when a chamber contracts against an increased afterload (pressure). |
|
|
Term
What is peripheral arterial disease?
What types exist?
What risks are associated w/PAD? |
|
Definition
It is a problem caused by occlusion of arteries in the legs typically due to atherosclerosis.
Claudication: muscle pain w/ exercise that relieves w/ rest.
Rest Pain: precedes tissues loss. Ischemia at rest.
Risks: 4-5 x more likely to die from CVD. 2-3 x mortality. Higher 5 year mortality than breast cancer. |
|
|
Term
| What happens to muscle in PAD? |
|
Definition
| Honycomb pattern, more adipose tissue, more inflammatory cells, more angular fibers (denervation), decreased strength and cross sectional area. |
|
|
Term
| What are the major risk factors for vascular disease? |
|
Definition
1. Smoking
2. Diabetes
3. Hypertension
4. Hyperlipidemia
5. Age
6. Homocysteinemia
7. Fibrinogenemia |
|
|
Term
What is the best indicator of PAD?
How do you treat PAD? |
|
Definition
Ankle brachial index.
Treatment: Exercise, risk factor modification, bypass, endovascular intervention, amputation. Future: stem cells, gene therapy. |
|
|
Term
What is mesenteric arterial disease?
What are the symptoms? |
|
Definition
Is occurs when arteries supplying the intestines are occluded.
Symptoms: Weight loss, severe pain w/eating. Vomiting, dizziness, & low BP (acidosis). |
|
|
Term
| What are the 3 important mesenteric arteries? |
|
Definition
1. Celiac axis
2. Superior mesenteric artery (supplies virtually all of small intestine and part of colon)
3. Inferior mesenteric artery (supplies part of the colon) |
|
|
Term
| What is special about the superior mesenteric artery? |
|
Definition
| It comes off the descending aorta at an angle, making it a common location for emboli to lodge. Emboli often come from the heart (Afib). |
|
|
Term
| What are the causes of acute mesenteric ischemia in order of frequency? What causes them? |
|
Definition
1. Embolic: from heart - Afib, MI, cardiomyopathy, etc. Often lodges distal to middle colic artery sparing the proximal jejunum and transverse colon.
2. Thrombotic: Atherosclerosis, hypercoaguable states. Blocks entrance and spares nothing.
3. Nonocclusive mesenteric ischemia: Intense vasospasm. Occurs in very sick pts. w/other issues (low flow, vasoconstrictors, atherosclerosis, etc.) Identify w/tapering.
4. Venous thrombosis: hypercoaguable (can be due to many causes). |
|
|
Term
| What is the clinical presentation of embolic and thrombotic acute/chronic mesenteric ischemia? |
|
Definition
Acute: Sudden pain out of proportion to exam - the key. Other GI symptoms.
Chronic: Pain after eating, weight loss, food fear. |
|
|
Term
| What is presentation of nonocclusive mesenteric ischemia and venous thrombosis? |
|
Definition
| These are usually critically ill patients. Abdominal pain/distension, other GI symptoms. Hard to diagnose. |
|
|
Term
| How do you treat the different types of mesenteric ischemia? |
|
Definition
Embolic: Embolectomy, anticoagulation, bowel resection (double check later).
Thrombotic: bypass, nutritional support, bowel resection (second look later).
Nonocclusive: correct underlying problem. Vasodilation.
Venous thrombosis: Fluids, anticoagulation. |
|
|
Term
| What does stroke have to do with vascular disease? |
|
Definition
| 30% of strokes are caused by cerebrovascular atherosclerosis. |
|
|
Term
| What are the risk factors for stroke? |
|
Definition
| TIA: transient ischemic attack (mini stroke), hypertension, smoking, diabetes, Afib, Carotid artery disease, hypercholesterolemia. |
|
|
Term
What is carotid artery disease?
Where does it occur?
How do they present?
What is a concern with using MR to image a stenosis? |
|
Definition
It is atherosclerosis of the carotid artery.
It occurs most often in the bulb. It is at a bifurcation and the bulbous area (baroreceptors) creates a lot of turbulence which is prime for atherosclerosis.
Presentation: Asymptomatic, TIA, stroke. Listen for bruits, imaging.
MR tends to over predict the degree of stenosis. |
|
|
Term
| How do you treat carotid artery disease medically? Surgically? |
|
Definition
Medical: Antiplatelet therapy
Surgical: Carotid endarterectomy, stenting (must use filters). |
|
|
Term
Where is the tear in aortic dissection?
What are the two classifications? |
|
Definition
It is a tear in the intima, leading to a false lumen in the tunica media.
Type A: Involve the ascending aorta (before the left subclavian). Life threatening. Present w/excruciating pain.
Type B: Only the descending aorta. Less life threatening. May lead to occlusion of branches of the aorta. |
|
|
Term
| What are the risk factors for aortic dissection? |
|
Definition
1. Hypertension - medial degeneration, intimal thickening, adventitial fibrosis.
2. Inherited connective tissue disorders (marfan's, etc)
3. Cocaine use.
4. Circadian pattern (more often in the early morning).
5. Other - surgical, trauma, pregnancy, etc. |
|
|
Term
What are the sequelae associated w/type A aortic dissection? Type B?
How do you treat them? |
|
Definition
Type A: Aortic valvue insufficiency, occlusion of coronary vessels, rupture into pericardium. All potentially lethal. Treat w/emergency surgery.
Type B: Intestinal ischemia, renal failure, paraplegia, lower extremity ischemia, rupture.
Treatment: No ischemia complications: medical treatment - lower BP, lower HR, decrease contractility, control pain. Ischemia, rupture, etc.: surgery. |
|
|
Term
What is an aneurysm?
What causes an abdominal aortic aneurysm (AAA)? |
|
Definition
It is defined as a 50% increase in diameter from the expected normal.
AAAs are caused by 1. Inflammation 2. Disruption of the connective tissue architecture (loss of elastin) 3. Medial thinning (impaired proliferation, apoptosis, and decreased density of SMCs). |
|
|
Term
| What are the 4 locations of AAAs? |
|
Definition
1. Infrarenal: below the renal arteries. 95%
2. Juxtarenal: up to the renal arteries.
3. Pararenal: including the renal arteries.
4. Suprarenal: extending above the renal arteries. |
|
|
Term
| How does inflammation related to AAAs? |
|
Definition
| Inflammatory cells lead to cytokines, which lead to MMPs, which degrade collagen and elastin. In AAA inflammatory cells are concentrated in the adventitia vs atherosclerosis where they're concentrated in the intima. |
|
|
Term
What are matrix metalloproteinases (MMPs)?
Where do they come from? |
|
Definition
They are zinc-dependent enzymes secreted as zymogens that degrade collagen, elastin and gelatin.
They come from fibroblasts, smooth muscle, inflammatory cells, and endothelium around the vaso vasorum. |
|
|
Term
What is MMP-2?
What is MMP-9? |
|
Definition
MMP-2: Attacks type IV collagen, elastin, and gelatin. Elevated in small, stable aneurysms.
MMP-9: Attacks elastin. Elevated in large, rapidly expanding aneurysms. Levels correlate w/ size. |
|
|
Term
What are risk factors for AAAs?
What is protective? |
|
Definition
Risk factors include smoking, age, family history.
Protective: Female, black, diabetes (no one understands why diabetes is protective). |
|
|
Term
What is a mycotic aneurysm?
What is an inflammatory aneurysm?
What two genetic disorders pre-dispose to aneurysm? |
|
Definition
Mycotic: an aneurysm caused by an organism. Gas bubbles in MRI.
Inflammatory: dense periaortic fibrosis. Stick to bowel.
Genetics: Marfan's syndrome, Ehlers-Danlos syndrome. |
|
|
Term
How does an AAA present?
When should it be repaired? |
|
Definition
Asymptomatic, distal emboli, abdomial/back pain, rupture: pain, hypotension, pulsatile mass.
Repair: <5.5cm - serial CTs. >5.5cm, or rapid expansion (>.5cm/yr), or symptoms - surgery. |
|
|
Term
|
Definition
T = P * r
As the aneurysm gets larger or BP increases the Tension goes up. Tension is directly related to the risk of rupture. |
|
|
Term
| What is the major concern when a patient undergoes cardiopulmonary bypass? |
|
Definition
| Inflammation. This can occur through hematologic effects (clotting) or physiologic effects. This inflammation can lead to hypoperfusion and tissue injury. |
|
|
Term
| What are the hematologic effects of cardiopulmonary bypass? |
|
Definition
1. Coagulation: through the intrinsic and extrinsic pathway
2. Cellular responses: neutrophil activation (leads to ROS, etc.), platelet activation, monocyte activation (later effect), endothelial cell activation. Can lead to SIRS.
3. Complement activation: MAC formation. Can lead to SIRS. |
|
|
Term
|
Definition
| Systemic Inflammatory Response Syndrome. This can be caused by cardiopulmonary bypass. We want to avoid it so much of what we do has to do with preventing these effects. |
|
|
Term
| What are the physiologic effects that can lead to hypoperfusion in cardiopulmonary bypass? |
|
Definition
| Microemboli, nonpulsatile flow, increased interstitial fluid, excessive hemodilution, temperature/pH mismatch, inflammation. All of these can lead to hypoperfusion and cause SIRS. |
|
|
Term
| What is the key to protect the patient during cardiopulmonary bypass? |
|
Definition
| Avoiding microemboli. All the strategies undertaken during surgery are part of this effort. |
|
|
Term
How do you stop the heart?
What is the mechanism?
Why do we do this? |
|
Definition
You infuse it with Potassium rich Cardioplegia. This causes the membrane to partial depolarize. The Na+ channel inactivation gate then remains closed, leading to cardiac arrest.
We do this to limit the heart's demand for oxygen to prevent ischemic damage. |
|
|
Term
| What causes reperfusion injury? |
|
Definition
| Increase in cytosolic calcium and generation of ROS. Apoptosis can then occur and is mediated by caspase 3. |
|
|
Term
What are the different types of bypass grafts?
Why would you use different ones? |
|
Definition
Arterial: Internal mammary (thoracic) artery. Most resistant to atherosclerosis. Can also use the radial artery, or the gastroepiploic artery but they are prone to vasospasm.
Venous: Saphenous vein graft. Prone to atherosclerosis. |
|
|
Term
| What factors determine whether a graft will remain patent? |
|
Definition
1. If it's arterial or not (arterial are more likely to stay open).
2. The amount of runoff flow (flow going through to other places). In decreasing order LAD, LCX, RCA.
3. The amount of collateral flow (the more flow through the graft the better to keep it patent). |
|
|
Term
| What are the tradeoffs between a mechanical and a tissue valve? |
|
Definition
Mechanical: very durable, but thrombogenic.
Tissue: non-thrombogenic, but prone to tears and calcification, especially in younger patients. Lasts ~ 10 yrs. |
|
|
Term
What are the 4 modalities of cardiac imaging?
Which are best at measuring anatomy? Function? |
|
Definition
1. Echo 2. Nuclear 3. MRI 4. CT
Anatomy: Echo, CT, MRI
Function: Echo, Nuclear, MRI |
|
|
Term
What scenarios do we need imaging for?
What modalities are best for each scenario? |
|
Definition
1. Coronary artery disease: Echo, Nuclear, CT
2. Valvular heart disease: Echo
3. Congestive heart failure: Echo (except for tissue characterization), Nuclear (not diagnosis or tissue characterization), CT (etiology & tissue characterization), MRI
4. Pericardial disease: Echo, CT, MRI
Other: Masses - MRI |
|
|
Term
| What is the cutoff for hypertension? |
|
Definition
|
|
Term
| What are effective lifestyle modifications to reduce hypertension? |
|
Definition
**Smoking Cessation***
1. Lose weight
2. DASH diet
3. Low sodium diet
4. Physical activity
5. Moderate alcohol |
|
|
Term
| What are the 5 categories of anti-hypertensives? |
|
Definition
1. Diuretics: Distal convoluted tubules, Loops, K+ sparing
2. Sympatholytic drugs: Centrally acting agents, alpha & beta blockers.
3. Renin-Angiotensin system: ACE-Is, ARBs
4. Calcium channel blockers
5. Vasodilators |
|
|
Term
| What are the 3 mechanisms of hypertension? |
|
Definition
1. Intravascular volume
2. Cardiac output
3. Peripheral vascular resistance |
|
|
Term
What are the 3 classes of diuretics?
Which drugs belong to which? |
|
Definition
Distal convoluted tubule: Thiazides
Loop diuretics: Furosemide (Lasix)
K+ sparing diuretics: Spironolactone |
|
|
Term
What is the mechanism of distal convoluted tubule diuretics?
What are the side effects? |
|
Definition
They block the Na-Cl symporter. Keeps Na in the tubule - water follows. These are the best, they decrease cardiovascular morbidity and mortality.
Side effects: Uric acid, ↓glucose metabolism, ↑cholesterol. |
|
|
Term
What is the mechanism of loop diuretics?
What are the side effects? |
|
Definition
They inhibit the Na-K-2Cl symporter in the ascending loop of Henle.
Side effects: Ototoxicity, hyperuricemia, ↑hypergylcemia, LDL, & trigylcerides. |
|
|
Term
What is the mechanism of K+ sparing diuretics?
What are the side effects? |
|
Definition
Triamterene & Amiloride inhibit Na+ channel in late distal tubule and collecting duct.
Spironolactone antagonizes the mineralocorticoid receptor in same place.
Side effects: Hyperkalemia, spironolactone: gynacomastia |
|
|
Term
| What is the mechanism of the centrally acting sympatholytic drugs? |
|
Definition
Clonidine: Stimulates the centrally located α2 receptor (feedback receptor) inhibiting more neurotransmitter release. Decrease vascular resistance.
Side effects: Sedation, dry mouth, depression |
|
|
Term
What is the difference between β1 and β2 receptors?
What about α1 and α2 receptors? |
|
Definition
β1 receptors are cardioselective - increase HR, etc. (blocked by Atenolol, Metroprolol). β2 are bronchodilation w/slight vasodilation.
α1 receptors are postsynaptic, α2 are feedback to the presynaptic neuron.
Note: alpha or beta blockers are not good as sole treatment for hypertension. |
|
|
Term
What are the calcium channel blockers?
What is their mechanism of action?
What are their side effects? |
|
Definition
Verapamil (heart), diltiazem (vascular & heart), dihyrdropyradines (vascular).
Mech: Prevent calcium influx, less contraction of smooth muscle.
Side effects: flushing, GERD |
|
|
Term
What are the peripheral vasodilators?
What are their mechanisms?
What are their side effects? |
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Definition
Hydralazine: relaxes arterial smooth muscle. Side effects: drug induced lupus.
Minoxadil: Activates a potassium channel in smooth muscle causing K+ efflux, leading to hyperpolarization and relaxation. Side effects: hypertrichosis, effusion.
Sodium nitroprusside: metabolized to NO - vasodilator.
Side effects: hypotension |
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Term
| How do you calculate ABI? |
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Definition
| Take the highest ankle number over the highest brachial number. Normal is >0.9. |
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Term
What happens to the chambers in stenosis?
In regurgitation? |
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Definition
Stenosis: Chamber before overfilled, chamber after under filled.
Regurgitation: Both the chamber before and after are over filled. |
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Term
What does volume overload cause?
What does pressure overload cause? |
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Definition
Volume: Eccentric hypertrophy (dilation + thick wall).
Pressure: Concentric hypertrophy. |
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Term
| What is Glanzmann's Thrombasthenia? |
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Definition
| It is hereditary platelet defect in the GP IIb/IIIa receptor. Abciximab acts at this receptor. |
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Term
| What are the terrible T's? |
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Definition
1. Tetrology of Fallot
2. Transposition of the great vessels
3. Truncus arteriosus
4. Tricuspid atresia
5. TAPVR (total anomalous pulmonary venous return) |
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Term
What's the difference between an NSTEMI and unstable angina?
Do you need positive troponins for STEMI diagnosis? |
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Definition
NSTEMI and UA have ECG changes, but NSTEMI has positive troponins.
You can diagnose a STEMI based on and ECG alone. It may be too early for troponins to show. |
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Term
| What is Pheochromocytoma? |
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Definition
| It's an adrenal tumor. It causes surges of catecholamines leading to severe hypertension, tachycardia, diaphoresis, and headaches. |
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Term
| How does hyperaldosteronism cause hypertension? |
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Definition
| Aldosterone leads to an increase in the Na/K pump in the DCT leading to water and Na retention, and hypokalemia, in addition to high BP. |
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Term
| What are signs of secondary hypertension? |
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Definition
| New onset hypertension before 30 or after 50. HTN refractory (resisting control or authority) to meds. |
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Term
What are the common causes of secondary hypertension?
Uncommon? |
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Definition
Common:
1. Intrinsic renal disease
2. Renal artery stenosis (renovascular disease)
3. Hyperaldosteronism
4. Obstructive sleep apnea.
Uncommon: Pheochromocytoma, aortic coarctation, Cushing's disease (glucocorticoid excess), thyroid issues. |
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Term
| How do you hear right sided murmurs better? |
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Definition
| They increase w/ inspiration. |
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Term
What are the 3 main types of shock?
How do you differentiate between them? |
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Definition
Cardiogenic shock: High CVP, low CO, high SVR.
Hypovolemic shock: Low CVP, low CO, high SVR.
Septic (or neurogenic, or anaphylactic) shock: low CVP, high CO, low SVR. |
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Term
| What causes cyanotic lesions? Acyanotic? |
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Definition
Cyanotic: Right to left shunting.
Acyanotic: Left to right shunting. Stenosis. |
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Term
What causes paradoxical splitting?
What causes wide splitting?
What causes fixed splitting? |
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Definition
Paradoxical: AS, LBBB.
Wide: PS.
Fixed: ASD. |
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Term
| What are the steps for diagnosing acute coronary syndromes? |
|
Definition
1. Symptoms
2. Risk factors
3. ECG
4. Troponins |
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Term
Lipidology: Which drug is best at lowering LDL?
Which drug is best at raising HDL?
What drug is best at lowering triglycerides?
Which drug lowers Lp(a)?
Which drug is the best additive agent to statins? |
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Definition
Lower LDL: Statins
Raise HDL: Niacin
Lowering triglycerides: Fibrates
Lowers Lp(a): Niacin
Additive: Bile acid sequestrants. |
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Term
Which hypertensive drugs should you use as first line agents?
Which should you not use? |
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Definition
Should: Thiazides, ACE-Is, Calcium channel blockers.
Not: Minoxadil, alpha blockers, etc. |
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Term
| What hypertensives are best for which comorbidities? |
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Definition
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Term
How do you measure O2 demand?
Supply? |
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Definition
Demand: The double product = Systolic BP * HR
Supply: Coronary Blood Flow = Pao/Rcoronary |
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Term
| What is the ARTS framework for adherence? |
|
Definition
Ask for patient's perspective/understanding.
Respond w/ empathy.
Tell your perspective w/ permission.
Seek solutions & comprehension. |
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Term
|
Definition
| (a/c)/(b/d) - The odd of having the exposure in cases over controls. |
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Term
| How do you convert odds to probability and back? |
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Definition
| Odds = p/(1-p). Probability = Odds/(1+odds) |
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Term
|
Definition
LR+ = sensitivity/(1-specificity)
LR- = (1-sensitivity)/specitifity |
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Term
Sensitivity = ?
Specificity = ? |
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Definition
Sensitivity = TP/(All+)
Specificity = TN/(All-) |
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