blood in disorders

8/8/2019 Blood in Disorders

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Blood lipids

Blood lipids (or blood fats) are lipids in the blood, either free or bound to other molecules. They

are mostly transported in a protein capsule, and the density of the lipids and type of protein

determines the fate of the particle and its influenceon metabolism. The concentration of blood lipids depends on

intake and excretion from the intestine, and uptake

and secretion from cells. Blood lipids are mainly fatty

acids and cholesterol. Hyperlipidemia is the presence of elevated

or abnormal levels of lipids and/or lipoproteins in the blood, and

is a major risk factor for cardiovascular disease.

Blood proteins

Blood proteins, also called serum proteins,

are proteins found in blood plasma. Serum total

protein in blood is 7g/dl. They serve many different

functions, including

circulatory transport molecules for lipids, hormones, vitamins and metals

enzymes, complement components, protease inhibitors, and kinin precursors

regulation of a cellular activity and functioning and in the immune system.


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Lipoproteins

A lipoprotein is a biochemical assembly that

contains both proteins and lipids whose function is

to transport water-insoluble lipids in the water-based bloodstream. The lipids or their derivatives

may be covalently or non-covalently bound to the

proteins. Many enzymes,transporters, structural

proteins, antigens, adhesins and toxins are

lipoproteins. Examples include the high

density (HDL) and low density (LDL) lipoproteins which enable fats to be carried in

the blood stream, the transmembrane proteins of the mitochondrion and the chloroplast, and

bacterial lipoproteins.

Classes of lipoproteins

Lipoproteins are divided into four main classes according to density: chylomicrons, VLDL, LDL,

and HDL. Lower-density lipoproteins are characterized by a higher fat-to-protein ratio (fat is

lighter) and therefore float more easily in the blood. Here are the basics about the four classes

of lipoproteins in order of increasing density:

1. Chylomicrons are the least dense of all the lipoproteins and are basically just big

balls of fat (triglycerides), with a makeup of about 90 percent fat, a touch of

phospholipids, some cholesterol, and a smidgin of protein.


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2. VLDL (very low-density lipoprotein) carries a great amount of fat, some

phospholipids, and cholesterol. The high fat content of VLDL makes a large quantity of this

lipoprotein in the blood undesirable.

3. LDL (low-density lipoprotein) or bad cholesterol has only a fraction of the fat

and double the protein of VLDL and is very high in cholesterol. This lipoprotein carries the

majority of cholesterol in the blood and is considered the unhealthy one.

4. HDL (high-density lipoprotein) or

"good" cholesterol is a spherical blob of mostly

protein (albeit a type different from that found in

LDL), some cholesterol, phospholipids, and

very little fat. The densest of all the lipoproteins,

HDL is the healthy one.


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What Is Cholesterol?

To understand high blood cholesterol, it is important to know more about cholesterol.

y Cholesterol is a waxy, fat-like substance that is found in all cells of the body. Your body

needs some cholesterol to work the right way. Your body makes all the cholesterol it

needs.

y Cholesterol is also found in some of the foods you eat.

y Your body uses cholesterol to make hormones, vitamin D, and substances that help you

digest foods.

Blood is watery, and cholesterol is fatty. Just like oil and water, the two do not mix. To travel in

the bloodstream, cholesterol is carried in small packages called lipoproteins (lip-o-PRO-teens).

The small packages are made of fat (lipid) on the inside and proteins on the outside. Two kinds

of lipoproteins carry cholesterol throughout your body. It is important to have healthy levels ofboth:

y Low-density lipoprotein (LDL) cholesterol is sometimes called bad cholesterol.

o High LDL cholesterol leads to a buildup of cholesterol in arteries. The higher the

LDL level in your blood, the greater chance you have of getting heart disease.


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y High-density lipoprotein (HDL) cholesterol is sometimes called good cholesterol.

o HDL carries cholesterol from other parts of your body back to your liver. The liver

removes the cholesterol from your body. The higher your HDL cholesterol level,

the lower your chance of getting heart disease.

Importance of lipoproteins

1. HDL, The Lifesaving Lipoprotein

HDL is manufactured in the small intestine and the liver, its primary source. As it moves through

the bloodstream, it takes in excess cholesterol that leaches out of tissue cells and, mostimportant, excess cholesterol building up in the inner arterial wall. HDLs unload this cholesterol

in the liver, where it is then excreted via bile, a process referred to as "reverse cholesterol

transport." Other lipoproteins bring cholesterol into the cells, so it is this reverse transport from

the cells to the liver that distinguishes HDL as the "good" cholesterol. An elevated level of HDL

has been associated with a reduced risk for heart disease. HDL confers heart-protective

benefits in four ways:

1. HDL circulates around the body, picking up excess cholesterol and bringing it back to the liver

for disposal (reverse cholesterol transport).

2. HDL is an antioxidant, capable of dismantling rogue free radical molecules that oxidize the

protein in the LDL particles-a contributing factor to atherosclerosis. (Oxidation is the same

process that produces rust on metals.)

3. HDL is an anti-inflammatory (like aspirin) and can decrease the inflammation linked with the

atherosclerotic process.

4. HDL lessens the ability of the blood to form clots, thus reducing the risk of heart attack or

stroke.


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2. Low Density Lipoprotein

Low-density lipoprotein (LDL) is one of the five major groups of lipoproteins, which in order of

size, largest to smallest, are chylomicrons,VLDL, IDL, LDL and HDL, that

enable lipids like cholesterol and triglycerides to be transported within the water-

based bloodstream. Blood tests typically report LDL-C, the amount of cholesterol contained inLDL. In clinical context, mathematically calculated estimates of LDL-C are commonly used to

estimate how much low density lipoproteins are driving progressions of atherosclerosis

Bad effects of lipoproteins

1. LDL, the Deadly Lipoprotein

LDL is the chief cholesterol carrier in the blood, ferrying approximately 70 percent of all the

blood cholesterol around the network of arteries. Basically, this lipoprotein is loaded with

cholesterol. Unlike HDL, LDL is not directly manufactured in the liver. Instead, a different type of

lipoprotein is first produced by the liver, the parent molecule called VLDL. After circulating

around the bloodstream, VLDL loses much of its fat (triglyceride) cache to various bodily cells to

become LDL. LDL is designed to take cholesterol to cells that have run short, as cells require

some cholesterol to maintain proper functioning. Typically, the LDL is taken into the cell and

broken down, and then the cholesterol is used to make membranes or hormones. However,

when the amount of LDL in the blood gets too high, the situation can become injurious.

2. VLDL(very low-density lipoprotein)

VLDL contains the highest amount of triglycerides. VLDL is considered a type of bad

cholesterol, because it helps cholesterol build up on the walls of arteries.

The deficiency (hypolipidemia) and excession (hyperlipidemia) of lipoproteins greatlyaffect us.

1. Hyperlipidemia

The term hyperlipidemia means high lipid levels. Hyperlipidemia includes several conditions, but

it usually means that you have high cholesterol and high triglyceride levels.


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High lipid levels can speed up a process called atherosclerosis, or

hardening of the arteries. Your arteries are normally smooth and

unobstructed on the inside, but as you age, a sticky substance

called plaque forms in the walls of your arteries. Plaque is made of

lipids and other materials circulating in your blood. As more plaque builds up, your arteries can

narrow and stiffen. Eventually, enough plaque may build up to reduce blood flow through your

arteries.

Atherosclerosis increases your risk of heart disease, stroke, and other vascular diseases.

Fortunately, you may be able to reduce high lipid levels and, therefore, prevent or slow the

progression of atherosclerosis. Lifestyle changes like exercising and eating a healthy diet can

also lower your lipid levels and are often the first step in treatment.

Causes and Risk Factors of Hyperlipidemia

Common secondary causes of hypercholesterolemia (specifically, high LDL cholesterol) include

hypothyroidism (that is, low thyroid hormone levels), pregnancy, and kidney failure.

Common secondary causes of hypertriglyceridemia include diabetes, excess alcohol intake,

obesity, and certain prescription medications (such as glucocorticoids and estrogen).

Hyperlipidemia, along with diabetes, hypertension (high blood pressure), positive family history,

and smoking are all major risk factors for coronary heart disease.

Symptoms of Hyperlipidemia

Hyperlipidemia usually has no noticeable symptoms and tends to be discovered during routine

examination or evaluation for atherosclerotic cardiovascular disease. However, deposits of

cholesterol (known as xanthomas) may form under the skin (especially around the eyes or along

the Achilles tendon) in individuals with familial forms of the disorder or in those with very high

levels of cholesterol in the blood. Individuals with hypertriglyceridemia may develop numerous

pimple-like lesions across their body. Extremely high levels of triglycerides may also result in

pancreatitis, a severe inflammation of the pancreas that may be life-threatening.

Diagnosis of Hyperlipidemia

Diagnosis is typically based on medical history, physical examination, and blood tests (done

after overnight fasting) in order to determine the specific levels of LDL cholesterol, HDL

cholesterol, and triglycerides.


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Treatment of Hyperlipidemia

It is necessary to first identify and treat any potential underlying medical problems, such as

diabetes or hypothyroidism, that may contribute to hyperlipidemia. Treatment of hyperlipidemia

itself includes dietary changes, weight reduction and exercise. If lifestyle modifications cannot

bring about optimal lipid levels, then medications may be necessary.

2. Hypolipidemia

Hypolipidemia is a decrease in plasma lipoprotein caused by primary (genetic) or secondary

factors. It is usually asymptomatic and diagnosed incidentally on routine lipid screening.

Treatment of secondary hypolipidemia involves treating underlying disorders. Treatment of

primary hypolipidemia is often unnecessary, but patients with some genetic disorders requirehigh-dose vitamin E and dietary supplementation of fats and other fat-soluble vitamins.

Hypolipidemia is a state where the fat level in the blood of a person falls to unusually low levels.

It is also termed as low blood cholesterol. Hypolipidemia is found in various forms and in many

diseases including hepatitis, cancer, liver diseases and severe malnutrition.

Hypolipidemia can be caused by a number of disorders including

hyperthyroidism,malnutrition, starvation, anaemia, disorders in the absorption of food by body,

various liver disorders, Tangier disease, and genetic disorders including abetalipoproteinemia

and hypobetalipoproteinemia.

Testing for hypolipidemia includes examining the levels of cholesterol andtriglycerides in the

blood. Normal total cholesterol level in one's blood should be below 200 mg/dl.

Lipoproteins Disorders

Lipoprotein disorder is a symptom of abnormal synthesis, processing, or catabolism of plasma

lipoprotein particles in the human body. This disorder can be inherited. Research indicates that

genetic factors that accelerate age associated cardiovascular changes are connected to

hyperlipidemia or cholesterol and familial history of the disorder. Disorders associated with

elevated levels of cholesterol alone are known as Fredrickson type Ila hyperlipoproteinemia.


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High Cholesterol levels present increased risk of ischemic heart disease. Elevated LDL

cholesterol is reflective of total elevated cholesterol. LDL cholesterol constitutes about 70% of

plasma cholesterol and is a constituent of the endogenous fat transport pathway. These are

formed by action of lipases on precursor particles. Carbohydrates and fats over and above body

requirement is converted into triglycerides by the liver and packaged into apolipoproteins and

secreted as VLDL particles. VLDL in turn is converted into IDL particles by a complex process

and fatty acids are liberated to form triglycerides, elevating levels of cholesterol.

Drug therapy is advocated for those with familial history of elevated cholesterol levels. Those

with genetic and familial history of cholesterol are treated with plasma exchange and liver

transplantation. A number of clinical trials conducted for gene therapy in the recent years have

been successful. In one such trial, Hepatocyes extracted from a portion of the liver were

genetically repaired in the laboratory and returned to the patients body. The cell infusions

resulted in a stable engraftment and the patients cholesterol levels dropped significantly. It is not

yet clear whether this therapy can be used widely, however, there is a distinct hope that more

efficient methods of gene replacement will be developed in the near future.

Low levels of HDL cholesterol are also considered a potential risk factor for CAD. Reduced HDL

cholesterol is also the most common type of lipoprotein disorder.

Lipid disorders include:

y Primary elevated cholesterol (LDL levels of more than 130 milligrams per deciliter, or

mg/dL);y Dyslipidemic syndrome (also called Syndrome X, a group of metabolic risk factors that

significantly increases the risk of developing CHD);

y Primary elevated triglycerides (triglyceride level as high as 1,500 mg/dL);

y Primary low-HDL syndromes (also called dyslipidemia or dyslipoproteinemia), in which

HDL is less than 35 mg/dL;

y Hyperlipidemia, or high cholesterol;

y Familial hypercholesterolemia, (a genetic disorder that increases total and LDL

cholesterol); and

y Familial hypertriglyceridemia, inherited high triglycerides.


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One of the blood disorder of blood lipoproteins is discussed below:

Tangiers disease

Definition

Tangier disease is a rare autosomal recessive condition characterized by low levels of high

density lipoprotein cholesterol (HDL-C) in the blood, accumulation of cholesterol in many organs

of the body, and an increased risk of arteriosclerosis.

History

Donald Fredrickson was the first to discover Tangier disease. He described this condition in

1961 in a five-year-old boy from Tangier Island who had large, yellow-orange colored tonsils

that were engorged with cholesterol. Subsequent tests on this boy and his sister found that they

both had virtually no high density lipoprotein cholesterol (HDL-C) in their blood stream. Other

symptoms of Tangier disease such as an enlarged spleen and liver, eye abnormalities, and

neurological abnormalities were later discovered in others.


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What other names do people use for Tangier disease?

y A-alphalipoprotein Neuropathy

y alpha High Density Lipoprotein Deficiency Disease

y Analphalipoproteinemia

y Cholesterol thesaurismosis

y Familial High Density Lipoprotein Deficiency

Disease

y Familial Hypoalphalipoproteinemia

y HDL Lipoprotein Deficiency Disease

y Lipoprotein Deficiency Disease, HDL, Familial

y Tangier Disease Neuropathy

y Tangier Hereditary Neuropathy

Signs and symptoms

Signs and symptoms of Tangier disease include a slightly elevated amount of fat in the blood

(mild hypertriglyceridemia); disturbances in nerve function (neuropathy); and enlarged, orange-

colored tonsils.A

ffected individuals often develop atherosclerosis, which is an accumulation offatty deposits and scar-like tissue in the lining of the arteries. Other features of this condition

may include an enlarged spleen (splenomegaly), an enlarged liver (hepatomegaly), clouding of

the clear covering of the eye (corneal clouding), and type 2 diabetes.


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The list of signs and symptoms mentioned in various sources for Tangier disease includes the

11 symptoms listed below:

y Low HDL level

y Mild hypertriglyceridemia

y High fat levels in blood

y Neuropathy

y Enlarged tonsils

y Orange or yellow tonsils

y Premature atherosclerosis

y Enlarged spleen

y Enlarged liver

y Cloudy cornea

y Early-onset cardiovascular disease

Atherosclerosis

As they age, those with Tangier disease often

develop atherosclerosis, the buildup of fatty

deposits and scar-like tissue in the linings of the

arteries. Premature coronary artery disease is six

times higher than average for those between 35 to

65 years of age with Tangier disease. Those with

the disease may also exhibit a slightly elevated

amount of fat in the blood, known as mild

hypertriglyceridemia

.

Ocular Signs and Symptoms

Subjects diagnosed with Tangier disease range in age from two to 67 years. To complicate

diagnosis, symptoms may vary more with progressing age. In the case of a 66-year-old male

diagnosed with the disease, the signs and symptoms resulting from the disease included ocular

complications such as corneal clouding, decreased corneal sensation and slowly progressive

visual impairment. Incomplete eyelid closure preceded corneal clouding.


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Nerve Function, Muscle Wasting and Other Signs and Symptoms

Other signs of Tangier disease include problems affecting nerve function that cause numbness,

tingling, pain, swelling and muscle weakness in various parts of the body. Some sufferers

experience widespread pain and temperature sensation loss over several parts of the body.Some exhibit progressive muscle wasting, including bilateral wasting of the hand muscles.

Other signs and symptoms that may occur include paralysis on both sides of the face, known as

facial diplegia; episodes of appendicular stabbing pain over several years; and Type 2 diabetes.

How common is Tangier disease?

Tangier disease is a rare disorder with approximately 100 cases identified worldwide. More

cases are likely undiagnosed. This condition is named after an island off the coast of Virginiawhere the first affected individuals were identified.

What genes are related to Tangier disease?

Mutations in the ABCA1 gene cause Tangier disease. This gene provides instructions for

making a protein that releases cholesterol and phospholipids from cells. These substances are

used to make HDL, which transports them to the liver.

Mutations in the ABCA1 gene prevent the release of cholesterol and phospholipids from cells.

As a result, these substances

accumulate within cells, causing

certain body tissues to enlarge

and the tonsils to acquire a

yellowish-orange color. A

buildup of cholesterol can be

toxic to cells, leading to

impaired cell function or cell

death. In addition, the inability

to transport cholesterol and

phospholipids out of cells

results in very low HDL levels,


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which increases the risk of cardiovascular disease. These combined factors cause the signs

and symptoms of Tangier disease.

How do people inherit Tangier disease?

This condition is inherited in an autosomal recessive pattern,

which means both copies of the gene in each cell have

mutations. The parents of an individual with an autosomal

recessive condition each carry one copy of the mutated gene,

but they typically do not show signs and symptoms of the

condition.

Causes

Scientists discovered that the cause of Tangier disease is involved with the intracellular

membrane trafficking of the HDL. Normally macrophages inside the cell have receptors that

bind the HDL. After the HDL is bound it is transported into the endosomes. The endosome is

transported through the cell without any degradation by the lysosome and the HDL is eventually

resecreted from the cell. It is during this cycle that there are problems for the Tangier disease

people. When the HDL is allowed to bind to the receptor monocyte, the two stick together but

they never separate. The HDL is not resecreted outside the cell. The data suggest that there is

a deficiency in the cellular metabolism of HDL in the Tangier monocytes. The HDL-monocyte

unit together also supports the observed condition of high concentrations of excess cholesterol

in body tissues.


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extensive accumulation of cholesterol. Arteriosclerosis may be treated

through angioplasty or bypass surgery. Angioplasty involves inserting a small, hollow tube

called a catheter with a deflated balloon through the groin or arm and into a clogged artery. The

balloon is then inflated which enlarges the artery and compresses the blockage.Coronary artery

disease can also be treated through bypass surgery, which is performed by taking a blood

vessel from another part of the body and constructing an alternate path around the blocked part

of the artery.

Complications

Low density lipoprotein levels low (serum or plasma)

Lymphadenopathy

Hypocholesterolemia

Peripheral neuropathy

Splenomegaly

Hepatomegaly

Corneal opacity

High density lipoprotein levels low (plasma or serum)

Autonomic neuropathy, peripheral

Intermediate density lipoprotein levels raised (plasma or serum)

Prevention

No known preventive measures as of this time.


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References

http://en.wikipedia.org/wiki/Blood_lipids

http://www.medterms.com/script/main/art.asp?articlekey=15389

http://ghr.nlm.nih.gov/condition/tangier-disease

http://www.wrongdiagnosis.com/medical/hypolipidemia.htm

http://wiki.medpedia.com/Tangier_Disease

http://www.ehow.com/list_6116515_signs-symptoms-tangier-disease.html

http://www.healthscout.com/ency/68/366/main.html

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