Dyslipidemia, emboli, arrhythmias- Bricks + Lecture Flashcards
_ deliver TGs and cholesterol from the intestines –> bloodstream and then TGs to peripheral tissues
Chylomicrons deliver TGs and cholesterol from the intestines –> bloodstream and then TGs to peripheral tissues
_ deliver TGs from liver –> tissues
Very low density lipoproteins (VLDL) deliver TGs from liver –> tissues
_ deliver cholesterol from liver –> tissues
LDL deliver cholesterol from liver –> tissues
_ deliver TGs to the tissues and cholesterol to the liver
IDLs deliver TGs to the tissues and cholesterol to the liver
_ deliver cholesterol from the tissues –> liver
HDL deliver cholesterol from the tissues –> liver
Acronym to remember Fredrickson primary lipid disorders
1 is LP
2 is LD
b adds V
3 is E
4 is more
Familial hyperchylomicronemia (Type I) is defect in _
Familial hyperchylomicronemia (Type I) is a defect in LPL (or ApoC2 deficiency)
* High chylomicrons
* High TGs
* Associated with pancreatitis
* May present with eruptive xanthomas
Familial hypercholesterolemia (Type IIa) is a defect in _
Familial hypercholesterolemia (Type IIa) is a defect in LDL receptors
* High LDL beginning from birth
* Caused by a mutation in LDL receptors
* Associated with atherosclerosis
Familial combined hyperlipidemia (Type IIb) is an increase in _
Familial combined hyperlipidemia (Type IIb) is an increase in LDL and VLDL
* The liver overproduces apoB-100
* Triglycerides are high
* Increased ApoB-100
* Metabolic syndrome (insulin resistance and obesity)
* Premature CAD
Familial dysbetalipoproteinemia (Type III) is a defect in _
Familial dysbetalipoproteinemia (Type III) is a defect in APOE
* Leads to poor lipoprotein clearance by the liver leaving chylomicrons and IDL in the circulation
* High IDL
* High chylomicrons
* High TGs
Familial hypertriglyceridemia (Type IV) is a an increase in _
Familial hypertriglyceridemia (Type IV) is an increase in high VLDL and TGs
* Pancreatitis
* May present with eruptive xanthomas
If _ is affected, there is a strong association with atherosclerotic heart disease
If LDL is affected, there is a strong association with atherosclerotic heart disease
Palmar xanthomas are notably only present in Fredrickson type _
Palmar xanthomas are notably only present in Fredrickson type III- familial dysbetalipoproteinemia
Eruptive xanthomas are associated with the disorders that increase _
Eruptive xanthomas are associated with the disorders that increase TGs
* Type I and type IV
Statin drugs inhibit the enzyme _
Statin drugs inhibit the enzyme HMG-CoA reductase
What are normal cholesterol levels?
Cholesterol is the precursor for_, _ and _
Cholesterol is the precursor for bile acids, steroid hormones and vitamin D
About 80% of our cholesterol is made via the (endogenous/exogenous) pathway
About 80% of our cholesterol is made via the endogenous pathway
What is the rate limiting step in the production of cholesterol?
Rate limiting step for cholesterol production: HMG-CoA reductase
* Target of statin drugs!
What is the process of cholesterol synthesis?
Acetyl coA + Acetyl CoA –>
Acetylacetyl CoA (+ acetyl CoA)–>
HMG-CoA –>
mevalonate –>
squalene
After HMG-CoA synthase brings in the third acetyl-CoA and forms HMG-CoA, the next enzyme is _ which reduces HMG-CoA into mevalonate
After HMG-CoA synthase brings in the third acetyl-CoA and forms HMG-CoA, the next enzyme is HMG-CoA reductase which reduces HMG-CoA into mevalonate
* This is the rate limiting step
* Target of statin drugs!
If too much cholesterol enters the liver we saturate the bile and end up with _
If too much cholesterol enters the liver we saturate the bile and end up with cholesterol gallstones
Triglycerides consists of _ bound to _
Triglycerides consists of three fatty acids bound to glycerol
The key mediators of the exogenous lipid pathway are _ because they are delivering dietary fats and cholesterols from the intestine to the bloodstream and then later to the tissues
The key mediators of the exogenous lipid pathway are chylomicrons because they are delivering dietary fats and cholesterols from the intestine to the bloodstream and then later to the tissues
Nascent chylomicrons will only contain _ Apo
Nascent chylomicrons will only contain Apo-B48
Abetalipoproteinemia is a mutation in MTP, the protein that loads _ onto chylomicrons and _ onto VLDL
Abetalipoproteinemia is a mutation in MTP, the protein that loads Apo-B48 onto chylomicrons and Apo-B100 onto VLDL
* The inability to form chylomicrons or VLDL imapirs absorption of fat
* Steatorrhea
* Deficiency in fat soluble vitamins
ApoA-1 is only found on _
ApoA-1 is only found on HDL
Most primary lipid disorders are autosomal dominant; however the two that are autosomal recessive and are more rare are _ and _
Most primary lipid disorders are autosomal dominant; however the two that are autosomal recessive and are more rare are type I and type III
Patients with high TGs are at risk for pancreatitis and also the development of a white ring around the edge of the iris known as _
Patients with high TGs are at risk for pancreatitis and also the development of a white ring around the edge of the iris known as corneal arcus
* Lipemia retinalis can also be seen where the retinal arteries appear yellow
Palmar xanthomas are only seen in _ type of dyslipidemia
Palmar xanthomas are only seen in type III dyslipidemia
Statin drugs are often prescribed to these patients; they work by _
Statin drugs are often prescribed to these patients; they work by inhibiting HMG-CoA reductase
Three antihyperlipidemia drug classes that lower the risk of ischemic heart disease include _ , _ , and _
Three antihyperlipidemia drug classes include
1. Statins
2. cholesterol-absorption inhibitors
3. PCSK9 inhibitors
Indications for administering statins
- Patients with ischemic heart disease
- LDL > 100 and high risk of ACS
- LDL > 100 and persistent nephrotic syndrome
Which step of cholesterol synthesis do statin drugs act on?
HMG-CoA –> mevalonate
This makes it harder for the liver to make its own cholesterol –> then the LDL receptors are upregulated –> lowers serum cholesterol
Why is the oral administration of statins advantageous?
Since statins are taken orally they undergo first pass metabolism –> they get processed by the liver –> this is a good thing because the target of statin drugs is the liver
Ezetimibe is a _ type drug that can also reduce the risk of ischemic heart disease, though less effectively than statins
Ezetimibe is a cholesterol-absorption inhibitor drug that can also reduce the risk of ischemic heart disease, though less effectively than statins
Ezetimibe interferes with the dietary absorption of cholesterol at the _
Ezetimibe interferes with the dietary absorption of cholesterol at the intestinal brush boarder
* It therefore lowers LDL
Two examples of PCSK9 inhibitors are _ and _
Two examples of PCSK9 inhibitors are Alirocumab and Evolocumab
PCSK9 is a circulating enzyme that binds to _
PCSK9 is a circulating enzyme that binds to LDL receptor and reduces the clearance of LDL from the body
* Blocking this enzyme increases LDL clearance by the liver
Bile acid sequestrants work by _ mechanism
Bile acid sequestrants work by decreasing absorption of bile acids –> liver receives less bile from the intestines and uses cholesterol to synthesize it –> this reduces cholesterol and LDL
Cholestyramine, colestipol, and colesvelam are all _ drugs
Cholestyramine, colestipol, and colesvelam are all bile acid sequestration drugs
Fibrates are drugs that increase TG degradation and clearance by _
Fibrates are drugs that increase TG degradation and clearance by activating PPAR-a which upregulates lipoprotein lipase (LPL)
Lipoprotein lipase is an enzyme found [location] and functions to degrade circulating TGs
Lipoprotein lipase is an enzyme found on the surface of endothelial cells and functions to degrade circulating TGs
_ drugs work by lowering the level of enzymes that make cholesterol
Omega-3 fatty acid drugs work by lowering the level of enzymes that make cholesterol (they also increase LPL activity)
* Eicosapentaenoic acid (EPA)
* Docosahexaenoic acid (DHA)
* Alpha-linolenic acid
How does niacin work?
Niacin works at the adipose tissue to inhibit hormone-sensitive lipase
* This decreases lipolysis and fatty acid release from adipose tissue
The only drug available that has a marked effect on increasing HDL is _
The only drug available that has a marked effect on increasing HDL is Niacin
Side effects of statins include _ and _
Side effects of statins include rhabdomyolysis and hepatotoxicity
Cholesterol absorption inhibitors can cause _
Cholesterol absorption inhibitors can cause hepatotoxicity and diarrhea
PCSK9 inhibitors can cause _
PCSK9 inhibitors can cause cough, flu sx, abdominal pain
Side effects of bile acid sequestrants include:
Side effects of bile acid sequestrants include:
* GI upset
* Decreased absorption of fat-soluble vitamins
* Decreased absorption of other drugs
Niacin side effects include _
Niacin side effects include:
* Facial flushing from prostaglandin release
* Hyperglycemia, hyperuricemia
Fibrates can cause _
Fibrates can cause dyspepsia, risk of gallstones
Omega-3 fatty acids can cause _
Omega-3 fatty acids can cause burping, fishy tase
The two types of arterial emboli are _ and _ with _ being more common
The two types of arterial emboli are thromboemboli and atheroemboli with thromboemboli being more common
_ originate from thrombi, tend to be single, and will generally lodge in medium to large vessels
Thromboemboli originate from thrombi, tend to be single, and will generally lodge in medium to large vessels
_ originate from microcrystals of cholesterol, tend to be multiple, and lodge in small vessels
Atheroemboli originate from microcrystals of cholesterol, tend to be multiple, and lodge in small vessels
The most common site of arterial emboli is the _ where atrial fibrillation can lead to loss of atrial contraction –> blood stasis –> thrombus formation
The most common site of arterial emboli is the left atrium where atrial fibrillation can lead to loss of atrial contraction –> blood stasis –> thrombus formation
* Less commonly, arterial emboli can come from the venous system via paradoxical embolism (patent foramen ovale)
What is the most common cause of atheroemboli?
Invasive vascular procedures (eg, arteriography) are the usual cause of atherosclerotic plaque destabilization, resulting in atheroembolism
Six P’s of acute limb ischemia
Pallor, Pain, Poikilothermia, Paralysis, Paresthesia, and Pulselessness
Signs of embolic occlusion of the central retinal artery
- Pale optic disk
- Cherry red spot on the macula
The three types of nonthrombotic emboli are _
The three types of nonthrombotic emboli are fat, air, and amniotic fluid emboli
* Less common ones include septic, tumor, and foreign body emboli
Venous air emboli lodge in the _ and may cause _
Venous air emboli lodge in the lungs and may cause dyspnea, chest pain, dizziness much like a PE
Arterial air amboli lodge in the _ and may cause _
Arterial air amboli lodge in the distal arteries and may cause stroke, limb ischemia
The two main causes of air emboli are _ and _
The two main causes of air emboli are medical procedures (placement of venous/arterial catheter) and scuba diving (if diver ascends too rapidly)
Decompression sickness occurs when the high pressures at depth (increase/decrease) the amount of gas dissolved in the blood
Decompression sickness occurs when the high pressures at depth increase the amount of gas dissolved in the blood –> if the diver ascends too rapidly, the increased nitrogen comes out of solution to form gas bubbles
During barotrauma, rapid ascent without exhalation expands the air in the lungs and causes _
During barotrauma, rapid ascent without exhalation expands the air in the lungs and causes rupture of alveoli –> entry of air inside the vasculature
Patients with venous air emboli should be placed in the _ position so that air is trapped in the _ and does not migrate into the lungs
Patients with venous air emboli should be placed in the left lateral decuvitus position so that air is trapped in the right ventricle and does not migrate into the lungs
Patients with arterial air emboli and scuba related emboli should be placed in _ position
Patients with arterial air emboli and scuba related emboli should be placed in supine position
Fat embolism occurs when fat globules are released into the venous circulation and lodge in the lungs; it is most common 24-72 hours after _
Fat embolism occurs when fat globules are released into the venous circulation and lodge in the lungs; it is most common 24-72 hours after fracture of a long bone (femur, humerus, pelvis)
* The marrow of these bones are particularly fatty
* Embolized fat is also able to degrade pro-inflammatory substances
What is amniotic fluid emboli?
Amniotic fluid containing fragments of fetal tissues enters the maternal circulation via a breach in placental membranes –> fragments travel to the maternal lungs and lodge in the pulmonary circulation
The most common cause of septic emboli is _
The most common cause of septic emboli is bacterial infective endocarditis
Four categories of arrhythmias
- Supraventricular arrhythmia originate above the cardiac ventricles (ex: afib)
- Junctional escape rhythm is bradycardia occurring at the AV junction (AV node and bundle of His)
- Ventricular arrhythmia occurs when the ventricular cardiomyocytes generate APs
- Heart block corresponds to failure or slowing of conduction at a point through the AV node, bundle of His, or bundle branches
Five underlying mechanisms by which arrhythmias normally occur
- Reentry
- Enhanced automaticity
- Decreased automaticity
- Triggered activity
- Conduction block
What is reentry?
Reentry refers to the continuous propagation of an electrical impulse traveling in a circuitous path –> results in the reactivation of the original site that generated the electrical impulse –> tachycardia
* Due to obstacle in the conduction system around which the impulse must travel
* Obstruction can be anatomic or functional
_ refers to an increased rate of generating action potentials
Increased automaticity refers to an increased rate of generating action potentials either in normal or abnormal pacemaker tissue
* Often due to increased sympathetic activity through catecholamine action
Triggered activity refers to _
Triggered activity refers to a condition when a normal action potential induces a spontaneous abnormal action potential immediately after it
* This “after-depolarization” can interrupt phase 2-4
* This is the mechanism of ventricular tachycardia
_ is when the AV node exceeds that of the SA node and the AV node takes over as the pacemaker
Junctional tachycardia is when the AV node exceeds that of the SA node and the AV node takes over as the pacemaker
* This is an example of increased automaticity
Sinus bradycardia is an example of decreased automaticity; explain
Sinus bradycardia involves a decreased rate of action potential generation by the SA node –> results in a slow heart rate
* The SA node will continue to set the pace but it will be at a reduced rate less than 60
What does it mean to have an incomplete conduction block?
The normal cardiac conduction system is disrupted and there is slow transmission due to the incomplete block
What does it mean to have a complete conduction block?
A complete conduction block means there is no transmission of electrical signal
Types of supraventricular arrhythmias
SVAs:
* atrial flutter
* multifocal atrial tachycardia
* AVNRT (supraventricular tachycardia)
* atrial fibrillation
General findings associated with supraventricular arrhythmias
Supraventricular arrhythmias:
* Generally less serious because the ventricle activity is conserved so blood is being pumped normally throughout circulation
* Have a rapid heart rate
* Normal QRS intervals
What do we expect to see in junctional arrhythmia on ECG?
Junctional escape rhythm:
* Heart rate is low at 40-60
* P waves are absent
* QRS normal
Atrial fibrillation
Ventricular tacycardia presents on ECG as _
Ventricular tachycardia presents on ECG as a series of wide QRS complexes
* Ventricular tachycardia and ventricular fibrillation are the two types of ventricular arrhythmias
* Both of these ventricular arrhythmias can present as cardiac arrest and be “pulseless”
Ventricular fibrillation on an ECG will appear with _
Ventricular fibrillation on an ECG will appear with no discernable pattern
Three types of heart block
- SA block: occurs between the sinus node and atrium
- AV block: occurs between the atria and ventricles
- Infra-Hisian block: occurs below the bundle of His
