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Hyperlipidemia

TEAM GENESIS

DEFINE

CAUSE

DIAGNOSIS

TYPES

PATHOGENESIS

EFFECT

CLINICAL MENIFESTATIONS (SIGNS & SYMPTOMS)

A Glimpse Through Foundation/Matrix

TG

Phospholipid

Cholesterol

Lipoprotein Types

Lipoprotein

Chylomicron

LDL

VLDL

IDL

HDL

Lipid Metabolism

Endogenous = Liver {De Novo Synthesis} (VLDL→IDL→LDL) [Apo B 100]

Exogenous= Intestine {From Diet}(Chylomicron→Chylomicron Remnants) [Apo B 48]

HDL[Apo C II ’Activate

Lipoproten Lipase’ , Apo E

’Liver Recognition’ ]

Apolipoprotein (Apo B48) organizes assembly in enterocyte’s golgi/ER

Picks up apo A,C and E in plasma (HDL)

Circulating chylomicrons interact at the capillaries of adipose tissue and muscle cells releasing TG to the adipose tissue to be stored and available for the body's energy needs.

The enzyme LPL

hydrolyzes the TG and free-fatty acids are released.

TG and cholesterol ester are generated by the liver and packaged into VLDL particles and then released into the circulation

VLDL is then processed by LPL in tissues to release fatty acids and glycerol.

The majority of the VLDL remnants are taken up by the liver via the LDL receptor, and the remaining remnant particles become IDL, a smaller, denser lipoprotein than VLDL.

The fate of some of the IDL particles requires them to be reabsorbed by the liver (again by the LDL receptor)

However, other IDL particles are hydrolyzed in the liver by hepatic-triglyceride lipase to form LDL

VIDEO

Dyslipidemia

Hyperlipidemia

Hypertriglyceridemia

Hypercholesterolemia

Hyperlipoproteinemia

Also Coexist In Combination

Hypolipidemia

Definition of DYSLIPIDEMIA: A condition marked by abnormal concentrations of lipids or lipoproteins in the blood

Definition of DYSLIPIDEMIA: Dyslipidemia is an abnormal amount of lipids in the blood. In developed countries, most dyslipidemias are hyperlipidemias

Hyperlipidaemia is just the medical word for a high level of lipid in the blood

Risk Factors

↑↑↑ TG (↑ Lipoprotein Syn)

↑↑↑ TC (LDL,IDL,VLDL)

↑↑↑ ( )

↓↓↓ HDL

Creamy Top (Supernatant)

{Indicative Of Chylomicron (Low Density, Tends To Float)}

Clear {Either Normal Or Indicative Of High Cholesterol Content (Why Is It Clear ?)}

Turbid/Milky/Cloudy {Indicative Of High TG But Specifically Refers To VLDL (Density Factors, Molecular Factors)}

Lipoprotein ElectrophoresisI. Chylomicro

n

II. LDLIIa LDLIIb LDL + VLDL

III. IDL

IV. VLDL

V. Chylomicron & VLDL

Types

Hyperlipidemia

Primary

Secondary{Common}

Primary Hyperlipidemia

LCAT

Mutations in the LDLR gene that encodes the LDL receptor protein, which normally

removes LDL from the circulation, or apolipoprotein B (ApoB), which is the part of

LDL that binds with the receptor

This defect prevents the normal metabolism of chylomicrons, IDL and VLDL, otherwise know as remnants, and therefore leads to

accumulation of their content

Utilization Dysfunction

Secondary

Hypothyroidism

When the thyroid slows down (hypothyroidism), it also slows down the body's ability to process cholesterol.

This processing lag is largely explained by a reduction in the number and activity of what are known as LDL receptors. LDL receptors help remove bad cholesterol from the body

When the number of receptors decreases, LDL accumulates in the bloodstream, acting to increase both LDL and total cholesterol levels.

Normal

Hypo

Nephrotic Syndrome/Renal Failure

Nephrotic syndrome is a nonspecific kidney disorder characterized by a number of signs of disease: proteinuria, hypoalbuminemia and edema. It is characterized by an increase in permeability of the capillary walls of the glomerulus leading to the presence of proteinuria

The increased loss of proteins in urine stimulates the liver to increase synthesis of proteins

Apolipoporteins are synthesised in increased quantities – especially apo B, apo C-II, and apo E which are used VLDL and LDL formation

Apoproteins associated with HDL synthesis – apo A-I and apo A-II usually remains normal

In addition to this, there is decreased lipid catabolism due to decreased activity of lipoprotein lipase

 Underlying mechanisms probably include overproduction by the liver, which concurrently increases albumin synthesis to compensate for renal protein wasting.

Cholestasis

In medicine, cholestasis is a condition where bile cannot flow from the liver to the duodenum. The two basic distinctions are an obstructive type of cholestasis where there is a mechanical blockage in the duct system such as can occur from a gallstone or malignancy, and metabolic types of cholestasis which are disturbances in bile formation.

Decreased cholesterol excretion (NB: Normally, 20% of secreted bile is excreted, most significant route of cholesterol excretion)---> Hypercholesterolemia

Obesity

People with excess visceral adipose tissue often have elevated triglyceride and low HDL-C levels.

Supply exceeds demand

Diabetes

Diabetes is due to either the pancreas not produce enough insulin, or because cells of the body do not respond properly to the insulin that is produced.

Diabetic ketoacidosis (DKA) is a potentially life-threatening complication in patients with diabetes mellitus. It happens predominantly in those with type 1 diabetes, but it can occur in those with type 2 diabetes under certain circumstances. DKA results from a shortage of insulin; in response the body switches to burning fatty acids and producing acidic ketone bodies that cause most of the symptoms and complications.

Increased Lipolysis

SIDE INFO: Diabetes insipidus (DI) is a condition characterized by excessive thirst and

excretion of large amounts of severely diluted urine, with reduction of fluid intake having no effect on the concentration of the urine.

Alcoholism

Hypertriglyceridemia associated with alcohol intake also mainly results from increased plasma VLDL. In some alcohol users, plasma triglyceride measurements can remain within the normal range because of an adaptive increase in lipolytic activity.

However, alcohol can also impair lipolysis, especially when a patient has a pre-existing functional deficiency of lipoprotein lipase, which leads to markedly increased plasma triglycerides

Alcohol has a significant additive effect on the triglyceride peak when it accompanies a meal containing fat, especially saturated fat. This results from a decrease in the breakdown of chylomicrons and VLDL remnants due to an acute inhibitory effect of alcohol on lipoprotein lipase activity.

Furthermore, alcohol increases the synthesis of large VLDL particles in the liver, which is the main source of triglycerides in the hypertriglyceridemia associated with chronic excessive alcohol intake.

Drugs

MoA Of Certain Drugs

Myeloma

In multiple myeloma, collections of abnormal plasma cells accumulate in the bone marrow, where they interfere with the production of normal blood cells. Most cases of myeloma also feature the production of a paraprotein—an abnormal antibody which can cause kidney problems. Bone lesions and hypercalcemia (high blood calcium levels) are also often encountered.

Distorts the normal plasma environment (Proteins are –vely charged)

Anorexia

Mean serum levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), ketone bodies, apolipoprotein (apo)-A1, B, C2, C3, E, and cholesterol ester transfer protein (CETP) activity were significantly higher in patients with Anorexia than in controls.

Serum levels of cholesterol, CETP, and apolipoproteins decreased after weight gain, indicating that cholesterol metabolism is accelerated in patients with Anorexia.

“Quoted from Dallas University Research”

Clinical manifestation

A xanthelasma is a sharply demarcated yellowish collection of cholesterol underneath the skin

Xanthoma tuberosum (also known as tuberous xanthoma) is characterized by xanthomas located over the joints

A creamy appearance of the retinal blood vessels that occurs when the concentration of lipids in the bloodsurpasses five percent.

Palmar xanthoma is clinically characterized by yellowish plaques that involve the palms and flexural surfaces of the fingers.[1]:531 Plane xanthomas are characterised by yellowish to orange, flat macules or slightly elevated plaques, often with a central white area which may be localised or generalised. They often arise in the skin folds, especially the palmar creases. They occur in hyperlipoproteinaemia type III and type IIA, and in association with biliary cirrhosis. The presence of palmar xanthomata, like the presence of tendinous xanthomata, is indicative of hypercholesterolaemia.

Eruptive xanthoma is clinically characterized by small, yellowish-orange to reddish-brown papules that appear all over the body.It tends to be associated with elevated triglycerides

Effects & Complications