Clinical Correlations III: Atherosclerosis Flashcards

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11
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ankle brachial index

A
  • normal 1
  • <0.4 = severe disease
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12
Q

Your patient has started Nicotine Patches and he is also watching his diet. Is there anything else your patient may due that would increase vascularization of the lower extremity and improve his claudication?

A

Exercise increases collateral formation and has been shown to improve claudication much more effective then platelet aggregation inhibitors clopidogrel and ASA.

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13
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•collateral formation

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14
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A 60 year old male with hyperlipidemia, DM Type 2, and HTN presents to your clinic with buttock pain and calf pain bilaterally. The pain is aggravated by activity such as walking and when he stops walking it resolves. He also complains of erectile dysfunction which is not improved with Sildenafil. On exam he has very weak pulses 1+ femoral bilateral and you can barely feel popliteal pulses. Ankle pulses are also barely palpable. Where do you think the stenosis is in the arterial tree?

1-popliteal artery • 2- femoral artery • 3- external iliac • 4-Aorta just before the bifurcation

A
  • 1-popliteal artery
  • 2- femoral artery
  • 3- external iliac
  • 4-Aorta just before the bifurcation
  • Internal illiac supplies pelvis including through pudendal artery penile artery
  • External iliac becomes common femoral
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15
Q

A 55 year old female presents with a 3x5 ulcer over the right medial malleolus. (see photo) She has 2+ pulses on both the right and left femoral, popliteal and PT/DP. Which of the following clinical factors would be most consistent with these findings?

• 1- A history of prior anti-coagulation • 2- A history of smoking • 3- A history of Von Willebrand Disease • 4- A history of hyperlipidemia

A
  • 1- A history of anti-coagulation
  • 2- A history of smoking
  • 3- A history of Von Willebrand Disease
  • 4- A history of hyperlipidemia
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16
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• A 70 year old male presents with a ulcer over the dorsum of left foot. (see photo) He has bilateral claudication and bilateral pain over the dorsum of the feet over the metatarsal heads at rest. He has a 50 pack year history and is trying to stop smoking. He has had 2 MIs in the past and has undergone 2 coronary artery stenting procedures. What physical finding is most consistent with this clinical picture?

A
  • 1- Left sided pulses (femoral, popliteal, DP/PT ) 1+ ; and all pulses on the right side 2+
  • 2- Left and right sided pulses- 1+femoral and popliteal, and absent ankle pulses
  • 3- Large varices over the back of the calf
  • 4- Large varices along the path of the great saphenous vein.
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17
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• Distal ulcers often represent arterial insufficiency, venous insufficiency or diabetic ulcer –try to identify the etiology of this ulcer:

A

•arterial

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18
Q

• Distal ulcers often represent arterial insufficiency, venous insufficiency or diabetic ulcer –try to identify the etiology of this ulcer:

A

•diabetic

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19
Q

• Distal ulcers often represent arterial insufficiency, venous insufficiency or diabetic ulcer –try to identify the etiology of this ulcer:

A

•venous

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20
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• How do you treat these ulcers? • If these patient needed surgery (colon resection) what do you think would be there major risk factor and why? • 1- arterial disease • 2- venous disease • 3- Type 2 DM

A
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21
Q

• A 35 year old with a very strong family history of MI and stroke. He is noted to have xanthomas over the elbow and eyelid. His labs are as follows. He has Type 2 DM He has a BMI of 38 • TG 850 mg/dL ( 60mg/dL) • LDL 120 mg/dL (normal < 100 mg/dL)

What would be a reasonable treatment plan?

A
  • Statin to lower TG and cholesterol
  • Add if target not reached HDL inhibits CETP-and TG: Fenofibrate/Niacin /Omega 3
  • Add Fenofibrate (increase LPL) or Niacin or Omega 3-
  • Increase HDL decrease TG (increases LPL activity)
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22
Q
  • Another doctor began 2 drugs one to lower his cholesterol and another drug to lower his TG and raise his HDL. • The following day the patient presents to the ED complaining of flushing, fever and light headedness. His BP is 120/65 and prior was 130/80 the day before. You obtain the above history. Which drug was most likely used to lower this patients TG?
  • 1- Atvorstatin • 2- Fenofibrate • 3- Niacin • 4- Omega-3
A
  • 1- Atvorstatin
  • 2- Fenofibrate
  • 3- Niacin
  • 4- Omega-3
23
Q

• The main mechanism of flushing vasodilation and decrease diastolic pressure is due to which of the following • 1- PGE2 • 2- IL-6 • 3- Thromboxane • 4- PGE1

A
  • The main mechanism of flushing vasodilation and decrease Diastolic pressure in this patient due to which of the following
  • 1- PGE2
  • 2- IL-6
  • 3- Thromboxane
  • 4- PGE1
24
Q
  • The same patient has a aortic stenosis murmur grade 2/6 noted in the chart from prior visits. Based on your knowledge of pressure gradients and murmurs what do you expect the murmur to be in the patient now after taking Niacin. • 1- 1/6 • 2- 2/6 • 3 - 3/6
  • If this was a mitral regurgitation murmur would the murmur be louder or softer in this same patient?
A
  • The same patient has a aortic stenosis murmur grade 2/6 noted in the chart from prior visits. Based on your knowledge of pressure gradients and murmurs what do you expect the murmur to be in the patient now after taking Niacin.
  • 1- 1/6
  • 2- 2/6
  • 3 - 3/6
  • Due to lower SVR increase pressure gradient between LV and aorta During LV contraction increase flow due to lower SVR–> increase murmur.

It would be softer because if you decrease SVR, pressure gradient increases between LV and Aorta (SVR). Increases flow forward across the AV less blood goes back into LA

  • Gradient between the LV and LA does not change
  • That is why in MR if the patient has HTN they should be treated aggressively. Improve foreword flow SV and CO
25
Q

• You are concerned about a patient with Type 2 DM who has a strong family history of MI and stroke. His TG level is 1200 mg/dL. His VLDL is 600mg/dL you wish to measure fasting levels of chylomicrons. • 1- Apo-B48 • 2- Apo–E • 3- Apo-A1 • Apo-B 100

A
  • You are concerned about a patient with Type 2 DM who has a strong family history of MI and stroke. His TG level is 1200 mg/dL. His VLDL is 600mg/dL you wish to measure fasting levels of chylomicrons.
  • 1- Apo-B48 (comes from enterocytes intestine )
  • 2- Apo–E
  • 3- Apo-A1
  • Apo-B 100
26
Q
  • A 45 year old with Type 2 is begun on Atvorstatin. He complains of muscle aches and cramping of the legs. You stop the medication. However you are worried about myalgia verses rhabdomyolysis.
  • Clinically and lab-wise how can we differentiate the two. - Myalgia versus rhabdomyolysis
A
27
Q

A 30-year-old man with a 5-year history of type 2 diabetes mellitus comes to the ED with severe dull epigastric pain that began suddenly this morning and gradually worsened. The pain is now 8/10 and radiates to his back and is slightly relieved by sitting up and leaning forward. He tried to eat earlier but that made the pain worse. He has no vomiting, diarrhea, change in bowel habit or history of weight loss. He does not drink alcohol or have a history of gallstones. He takes metformin for the DM but no other medications. He checks his blood sugar only rarely. The last check was several weeks ago and his blood sugar was markedly elevated at 350 mg/dL. On examination, vital signs are normal except tachycardia of 110. The patient weighs 190 kg and has a high BMI. There is marked tenderness in the epigastrium but no other positive findings. Blood is sent to the lab. The tube of his blood is shown following centrifugation.

A
28
Q

A 25-year-old graduate student is seen in clinic for evaluation of hyperlipidemia. His family history is positive for early cardiovascular disease and high cholesterol. His father has a history of high cholesterol and an MI at 38. An uncle died of a “heart attack” in his forties and an aunt had a stent placed before age 50. Physical examination is normal except for the skin changes shown. The patient’s lipid panel shows total cholesterol of 520 mg/dL (normal < 200) with an LDL cholesterol of 450 mg/dL. What is causing this severe elevation of LDL and total cholesterol in this young man?

  • A. Elevated VLDL secretion
  • B. Increased number of LDL receptors
  • C. Decreased LDL clearance
  • D. Lipoprotein lipase deficiency
A
  • A. Elevated VLDL secretion
  • B. Increased number of LDL receptors
  • C. Decreased LDL clearance
  • D. Lipoprotein lipase deficiency
29
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A
30
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Lipoproteins

A

•particles travel in the blood made up of a central core of fats which include cholesterol esters and Triacylglycerol (TGs )and outer cover of proteins and phospholipids. Allowing intra-vascular transport due to solubility. (VLDL, IDL, LDL, HDL, Chylomicrons, Chylomicron Remnants)

31
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Apoproteins

A

•act as ligands for lipoprotein metabolism and activate and inhibit key enzymes involved in lipid metabolism.

32
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LDL

A
  • major lipid - cholesterol
  • Apo B-100
  • pro-atherogenic

Clearance of LDL from the blood depends on the number of LDL receptors–> upregulate the LDL-R–> increase LDL-C clearance

• Decrease in intra-hepatocyte cholesterol upregulates LDL-R

33
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Fat Metabolism

A
  • Ingested Fat-(non-soluble)–> enterocyte–>chylomicron (Soluble ) –> Lymph (thoracic duct)–> right atrium –> circulation –> muscle and adipose and peripheral tissue-(LPL)-> TG –> FFA for energy via LPL (Lipoprotein Lipase)
  • Triglycerides (TG) are used as an important energy source via conversion by LPL to FFA (Free Fatty Acids) in muscle and adipose tissue • Cholesterol is used for bile formation in the liver, cell membrane integrity
34
Q

remnant chylomicron

A

TGs are removed through Lipoprotein lipase (LPL) and a Remnant Chylomicron is left which is mainly cholesterol and less TGs however is very pro-atheromatous

35
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Mechanism of Statins

A

Liver is the major site of lipid metabolism

  • lower cholesterol levels in the hepatocyte
  • This increases LDL-R _Cholesterol is crucial in the liver for formation of bile
  • Also hepatocytes secrete free cholesterol directly into bile
  • Increase in LDL – R increases LDL clearance

Complications of Statins:

1- Muscle Myalgia versus rhabdomyolysis CPK • 2- Liver ALT/AST

36
Q

HDL

A
  • Reverse Cholesterol Transport
  • Reverse Cholesterol Transport involves Cholesterol movement from cells (macrophage) endothelium to HDL -> Liver where cholesterol is secreted into the Bile or converted into bile acids–> Intestine
37
Q

We have talked about Statins and their proved role in lowering LDL-C and the benefit in reducing coronary artery complications such as MI. • What other sites might be targeted in the metabolism of LDL-C that would lower LDL levels?

A
  • 1- Statins block formation of cholesterol via HMG-CoA reductase Inhibition–>decrease cholesterol –> increase LDL-R
  • 2- NPC1L1 transporter - controls cholesterol absorption from GI tract Ezetimibe
  • 3- PCSK9 promotes degradation of LDL-R –Inhibitors of PCSK9 Alirocumab, Evolocumab increase LDL-R duration –> decrease LDL-C
38
Q

Clinical manifestations of atherosclerosis Lower extremity

A

• Atherosclerosis affects all of the arteries and is most severe at areas in the artery where there is maximal turbulence –> damages intima __> Cholesterol enters as LDL and damages the intima –> inflammation –> Plaque

39
Q

PVD

A
  • Claudication - arterial O2 delivery does not meet 02 requirement Calf Pain during walking (02 requirement increases) like angina stops when at rest
  • Rest Pain –more severe stenosis pain at rest over the dorsal feet
  • Ulcers that do not heal due to such poor arterial flow
40
Q

WHAT ARE THE MOST IMPORTANT LIPOPROTEINS and APO-protein ?

A
  • HDL Cholesterol Apo A-l
  • LDL Apo B-100 (binds liver LDL-R)
  • VLDL and IDL APO-E (binds liver receptor E cleared)
  • Chylomicrons Apo B -48
41
Q

LDL Mutations that increase LDL

A

• 1- Defective LDL-R *****

2- Defective formation of ApoB-100 can not bind liver and be cleared into bile

• MI, tendon xanthoma corneal arcus

42
Q

HDL Mutations

A

HDL immature–> Mature need cholesterol transfer

• 1- Apo-A-l deficiency most important /Binding SR-B1

2- ABCA1 /ABCG1 deficiency

3- LCAT deficiency (APO A-1)

• Apo A-I mutations cause the most elevation in cardiovascular risk compared with other gene mutations in HDL metabolism

43
Q

Familial hyperchylomicronemia l

A
  • Apo B-48 ** chylomicrons marker synthesized in intestine
  • 1- Hyperchylomicronemia – lipoprotein lipase deficiency or Apo C-ll
  • Need lipase to break of FFA from TG in Chylomicrons –> hypertriglyceridemia
  • Apo C-ll co-Factor for Lipoprotein lipase
44
Q

Clinical picture Hyperchylomicronemia (increase TG)

A
  • Pancreatitis****due to hyperlipidemia always think TG markedly elevated
  • Hepato-splenomegaly
  • Xanthomas
  • Lipid supernatant (decrease in density )
  • Increase risk Atheroma formation
  • Lab increase TG, chylomicrons (Apo B- 48)
45
Q

Familial Hyperlipidemia -ll

A
  • ll A- Familial Hypercholesterolemia
  • ll B- Familial combined Hyperlipoproteinemia
46
Q

Familial Hypercholesterolemia llA

A
  • Defective LDL-R classic llA
  • Or
  • Less common Defective Apo B 100 less common needed for binding LDL-R
  • Labs– LDL, total cholesterol, ONLY PURE ELEVATION OF CHOLESTEROL
  • Symptoms MI before 30 years old, xanthomas (lipid filled macrophages), corneal arcus
47
Q

Familial Hyperlipidemia llB or Familial combined hyperlipidemia

A

• Increase LDL and VLDL increase TG and total cholesterol

48
Q

Familial Hyperlipidemia lll Dysbetalipoproteinemia

A
  • Defective Apo-E2 prevents full removal of TG from VLDL–> IDL and binding of IDL to Receptors in the liver –> increased IDL
  • cholesterol and TG elevated
  • VLDL – –> IDL –> decreased LDL
  • Labs- IDL *** therefore TC and TG increased
  • Clinical Picture –atheroma formation, xanthomas
  • Predisposing factors DM-Type2 Insulin resistance, obesity
49
Q
A

Pathognomonic for Hyperlipidemia lll

50
Q

Familial Hypertriglyceridemia lV

A
  • Hepatic over-production of VLDL • Labs -VLDL, TG
  • Hypertriglyceridemia –> acute pancreatitis
  • Cause unknown
51
Q

Mixed Hypertriglyceridemia V

A
  • Increase VLDL • Increase chylomicrons like Familial Hyperlipidemia 1 however this more often has associated factors such as:
  • DM obesity Insulin resistance
  • Increase TC
  • Versus Familial this may not have LPL deficiency and or Apo C ll problem
52
Q

Other Drugs for Hypertriglyceridemia

A
  • Fenofibrate –> mechanism action
  • Lower TG and VLDL thus lower cholesterol VLDL Chylomicrons rich TG
  • Increase activation LPL-> decrease TG level –> increase FFA entrance into peripheral muscle and fat
  • Decrease cholesterol synth. Liver
53
Q

Niacin

A
  • Adipose tissue releases free fatty acids that drive the production of triglycerides in the liver. Niacin has two mechanisms by which it reduces triglyceride levels. It blocks the release of free fatty acids from adipose tissue, reduced rate of secretion of VLDL particles.
  • 1- increases HDL
  • 2- decreases synthesis VLDL in liver
  • 3- decrease LDL
  • Side effects flushing PG E2 and D2 block aspirin ibuprofen
54
Q

Omega 3

A
  • Omega-3 fatty acids act similarly to fibrates to reduce triglyceride levels. Although they operate differently in the liver, prescription omega-3 fatty acids inhibit the release of triglycerides from the liver, reducing the number of VLDL particles. They also stimulate lipoprotein lipase, which increases the rate of clearance of triglycerides from the plasma.
  • Decrease VLDL release from liver
  • Increase LPL activation