Lipid Disorders Pathophysiology and their Causes (Acquired and Inherited)

Quick Introduction

Dyslipidemia is the imbalance or abnormal concentration of cholesterol, triglycerides, and lipoprotein molecules (low-density lipoprotein and high-density lipoprotein). The Low-Density Lipoprotein (LDL) is increased, while the High-Density Lipoprotein (HDL) is reduced. ^ncbi. Hyperlipidermia has to with bloodstream lipid, and this refers to an increase/elevation in lipid level/concentration in the bloodstream/body increasing the total cholesterol (TC), Low-density Lipoprotein (LDL) and/or triglyceride (TG) and reducing high-density lipoprotein (HDL).^ncbi. Hypercholesterolemia is the increase in total cholesterol molecule level in the body. A patient is said to have hypercholesterolemia if the patient's Low-Density lipoprotein cholesterol is greater than 190mg/dL or 200mg/dL depending on the book, article, or the journal you are using, or greater than 160 mg/dL with a major risk factor such as age, smoking, or diabetes, or higher than 130 mg/dL with about two cardiovascular risk factors such as hypertension.^ncbi. Hypertriglyceridemia refers to the increase in Triglycerides in the body. An increase in Triglyceride above 150mg/dL will result in hypertriglyceridemia, but the numbers can increase with a triglyceride level of over 500mg/dL being a very high level of hypertriglyceridemia.^ncbi.

Physiology Explained

When we eat fatty foods, bile and bile acids are being secreted by the gallbladder. The bile acids bind with the cholesterol, and free fatty acids to become micelles which will be absorbed across the gastrointestinal tract until they get to the lymphatic circulation.^ncbi

In the Lymphatic circulation, the cholesterol, triglycerides, and apolipoprotein B 48 are packed to become chylomicrons which are then carried to the blood where they become metabolized by lipoprotein lipase to release free fatty acid that will be taken to adipose and muscle tissues. When the free fatty acids are taken away, the chylomicron remnant is taken by the liver, digested, and repackaged to make very low-density lipoproteins (VLDL) molecule. The very low-density lipoproteins (VLDL) also carry triglycerides in excess as well as cholesterols and go through the bloodstream where the Lipoprotein lipase releases free fatty acids, leaving the chylomicron remnant with more cholesterol and fewer triglycerides which will be taken back to the liver to become low-density lipoprotein (LDL) which is then deposited in different tissue, and vessels causing Atheroclerosis.^{ncbi, ncbi2}. In the liver, another set of lipoproteins is the nascent high-density lipoprotein (HDL) which possesses lots of lipoproteins but no cholesterol. It is responsible for taking plaques from the vessels to the liver where they can be reused.^{ahajournals, spandidos.}

Pathophysiology of Lipid Disorders

Lipid disorders can be inherited, Acquired causes. When it is familial, we can use the Frederickson classification which has the type I, type IIa, type IIb, type III, type IV, and type V (depending on the source it could end at type IV or V). With Type I, there is an increase in chylomicrons in the blood where the triglycerides are not allowed to flow out as free fatty acids. Associated diseases will be Lipoprotein lipase deficiency and apolipoprotein C-II deficiency. Type IIa has an increase in Low-Density Level (LDL) Fat as the LDL receptor is damaged or defective, not taking LDL molecules thereby causing an increase of LDL in the blood and cholesterol in the vessels of the body. Type IIa diseases are Familial hypercholesterolemia, polygenic hypercholesterolemia, nephrosis, hypothyroidism, and familial combined hyperlipidemia. Type IIb with LDL receptors are not present or not functioning, leading to the inability for LDL to reach the liver cells, and causing an increase in LDL and VLDL. An example of Type IIb Disorder is Familial combined hyperlipidemia. Type III disorder allows an increase in intermediate-density lipoproteins (IDL). This occurs as a result of a defect in the APOE protein which is located on the VLDL and the Chylomicron molecule thereby preventing the uptake of the chylomicron into the liver causing a buildup of IDL in the blood. A Type III disorder is Dysbetalipoproteinemia. With Type IV disorder there is an increase in VLDL as a result of the liver creating a lot of it causing a lot of triglyceride in the blood. This will lead to Familial hypertriglyceridemia, familial combined hyperlipidemia, sporadic hypertriglyceridemia, and diabetes. Type V has an increase in Chylomicrons and VLDL molecules in the blood. Disease-associated with Type V disorder is Diabetes.^{gpnotebook, biomedcentral.}

Lipid disorders can also be a result of acquired causes. These causes are not a result of genetic transfer but rather caused by acquired conditions or diseases. First, I will look into people with Diabetes.

Insulin works on lipoprotein ripping out triglycerides from chylomicron and VLDL and converting them to free fatty acids for energy or depositing them into fat tissues. People with diabetes are unable to perform this activity as a result of a problem with their insulin. The lipoprotein lipase will not respond properly to the insulin which leads to a decrease in the lipoprotein lipase which will lead to the reduction or less conversion of triglycerides from the CLDLs and Chylomicron into free fatty acids. This leads to excess triglycerides in the blood, as well as LDL in the blood as the VLDLs convert to LDLs.^{ncbi 1, ncbi 2, pubmed, ncbi3.}

Another acquired cause is Hypothyroidism. Thyroid act on the liver to regulate the LDL receptor so LDL can be retaken to make VLDL but when with hypothyroidism where the T3 and T4 levels are low, the LDL receptors won't regulate properly causing the LDL to stay in the bloodstream instead of being taken by the liver.^ncbi

With Nephrotic syndrome, you should guess it has something to do with the nephron in the kidney. With nephrotic Syndrome, the patient losses lot of Albumin with Urine as a result of damage to their glomeruli which will lead to a lack of albumin in the blood. Albumin is responsible for carrying free fatty acids which will lead to the reduction of free fatty acids in the blood. This causes the liver to make more albumin but at the same time creates more LDL which will later become VLDL, then increases the amount of cholesterol in the blood.^{karger, ncbi, ncbi.nlm.}

Drugs such as Beat Blocker, Estrogen, and Thiazide also can also cause lipid disorders, and also increase in weight, and an increased diet with cholesterol can lead to lipid disorders. This will lead to an increase in LDL, Chylomicron, VLDL, and cholesterol in the bloodstream.^{ncbi,pubmedncbi 2}

Image Reference

• Image 1|| FLickr || Fat and Fast Food
• Image 2 || Wikimedia Commons || Lipid and bile salts