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Disorders of Lipid Metabolism
Lipids are a group of heterogeneous substances metabolically active, constantly circulating in the
vascular channels and existing in a state of dynamic equilibrium between peripheral tissues,
gastrointestinal tract and liver
...

Increasing or decreasing levels of lipids cause various health effects in the human body which
are called disorders
...

The body requires the useful fatty acid high density lipoprotein, which helps to transport bad
cholesterol out of the body
...

Disorders of lipid metabolism often cause atherosclerotic vascular diseases including thromboembolic
cerebrovascular disease, ischemic heart disease and peripheral vascular disease
...

Lipid metabolism disorders can be divided into:
1
...

2
...

Irrespective of the underlying mechanism of lipid disorder, the biochemical abnormalities will
manifest either as hypertriglyceridemia or hypercholesterolemia or a combination of both
...

These disorders can be as a result of a single gene mutation or may be polygenic in origin
...
It was thought to be inherited as an autosomal
dominant trait but recent studies have not supported the concept of simple dominant inheritance,
although genetic factors are very much responsible in expression of this phenotype in affected
families
...

There is no hyperlipidemia at childhood but young adults suffering from FCH may manifest in
early middle age with either mild hypercholesterolemia, triglyceridemia or both
...

Diagnosis is often prompted when an individual has mild hyperlipidemia with changing patterns
of lipids in the blood
...


Familial Hypertriglyceridemia
This is a common disorder inherited as an autosomal dominant trait due to mutation of a single
gene (not yet identified)
...
Neither the very low density lipoprotein molecule nor lipoprotein lipase has been found
to be abnormal in these patients
...

Plasma triglyceride levels vary from 200 to 500 mg/dl and the typical patients with familial
hypertriglyceridemia
usually
has
obesity
and
hyperinsulinemia
associated
with
hypertriglyceridemia
...
These patients when they have other
metabolic abnormalities like diabetes mellitus, hyperuricemia, hypothyroidism or disorders such as
hypertension or take excess alcohol will have precipitation of severe hypertriglyceridemia and
pancreatitis
...
Alcohol intake, oral
contraception pills in women and excess calories have to be restricted
...

Familial hypercholesterolemia (FH)
This is the commonest type of primary disorder of cholesterol mechanism
...
The defect makes the body unable to remove low density
lipoprotein cholesterol from the blood
...
This may lead to narrowing of the arteries from atherosclerosis at an early age
...

In rare cases, a child may inherit the gene from both parents
...
The risks for heart attacks and heart disease are high even
in childhood
...

Symptoms that may occur include:
▪ Fatty skin deposits called xanthomas over parts of the hands, elbows, knees, ankles, and around
the cornea of the eye
...

▪ Chest pain (angina) or other signs of coronary artery disease may be present at a young age
...

▪ Sores on toes that do not heal
...

A physical exam may show fatty skin growths called xanthomas and cholesterol deposits in the
eye
...
There may
be:
▪ A strong family history of familial hypercholesterolemia or early heart attacks
...

People from families with a strong history of early heart attacks should have blood tests done to
determine lipid levels
...

▪ Genetic test for the defect associated with this condition
...

A diet low in cholesterol and saturated fat and rich in unsaturated fat may help control low density
lipoprotein levels
...

Polygenic hypercholesterolemia (PHC)
This is the most prevalent form of hypercholesterolemia with raised low density lipoprotein
cholesterol levels but is not due to any one identifiable cause
...
The mutation is detected using 12 single
nucleotide polymorphisms
...

Complications may include:
▪ transient ischemic attack
▪ stroke
▪ coronary artery disease
▪ peripheral artery disease
▪ Mortality
...

Most patients with polygenic hypercholesterolemia respond to dietary restriction of cholesterol intake
while some may require treatment with statins and resins
...
This results in the buildup of lipids in the body (hyperlipidemia) and can
lead to the development of multiple small, yellow skin growths (xanthomas)
...
Hyperlipoproteinemia type III affects 1-5,000
to 1 in 10,000 people in the general population
...
It is transmitted as a single gene defect, this
leads to partial catabolism of very low density lipoprotein with consequent accumulation of remnants
in plasma which leads to a rise in both cholesterol and triglyceride levels
...

The symptoms of hyperlipoproteinemia type III may vary from person to person
...
Symptoms of hyperlipoproteinemia type III often
do not appear unless additional conditions are present such as diabetes, obesity, or hypothyroidism
...


The defect lies in ApoE gene, where a mutation or polymorphism leads to production of abnormal
ApoE with impaired binding capability to its receptor
...
The ApoE is a very important constituent of intermediate density
lipoprotein/remnants and binds to receptor on hepatocytes as well as low density lipoprotein receptors
on peripheral tissues
...
Co-existent diabetes
mellitus, hypothyroidism and obesity are seen in many patients with this lipid disorder
...

In such patients, a proper evaluation should be done to exclude and treat underlying hypothyroid
state or diabetes mellitus
...
Resins are however contraindicated in this disorder
...
However this is a rare autosomal recessive disorder where parents
are obligatory heterozygotes and do not have any clinical manifestation
...
By adolescence they
have hepato-splenomegaly with foam cell (lipid laddened macrophages) infiltration into bone
marrow
...
Pale retina or lipemia retinalis is detected
on ophthalmoscopy
...
Prima facie diagnosis
is done looking at the plasma of the patients kept at 4oc overnight where a white creamy layer
accumulates at the top of the tube
...

The mainstay of treatment is fat free diet i
...
Total fat intake restricted to 20 g/day and plasma
triglyceride levels kept below 1000 mg/dl
...
They also have to be
supplemented with fat soluble vitamin
...
Due to deficiency of Apo
CII the activity of lipoprotein lipase is suppressed and so both very low density lipoprotein and
chylomicrons accumulate in the blood
...
This lipid disorder is however rare and is transmitted as an autosomal recessive condition
...
Absence of Apo CII is established by gel electrophoresis of very low density lipoprotein
apoproteins
...

Besides post-heparin rise in lipoprotein lipase is normal in these patients
...

SECONDARY HYPERLIPOPROTEINEMIAS
These are acquired hyperlipoproteinemias caused by factors such as lifestyle example smoking,
consumption of food high in saturated fats, obesity and a sedentary lifestyle
...

Diabetes Mellitus
Uncontrolled glycemic state in patients with type 2 diabetes leads to both excess production of
very low density lipoprotein as well as poor peripheral clearance causing endogenous
hypertriglyceridemia
...
Those on high
fat and richer diet may present with combined hyperlipidemia
...
This causes suppression of their function along with enhanced oxidation and
destruction of these patients
...

Nephrotic Syndrome
In conditions like nephrotic syndrome and chronic renal disease, there is excess secretion of very
low density lipoprotein along with decreased catabolism which leads to type IV hyperlipidemia
...
The most important are the oral contraceptives which can enhance
very low density lipoprotein production from liver and produce hypertriglyceridemia
...

Similarly excess of alcohol intake induces fatty acid synthesis in liver via suppression of fatty
acid oxidation
...

Furthermore, there is also slower degradation of chylomicron and so Type V hyperlipidemia occurs
in these patietns
...
If after such appropriate intervention the lipid profiles
remain elevated, lipid lowering drugs may be instituted
...
The table is
based on the changes in the concentration of the various types of lipid
...
These
numbers can change from year to year, so getting annual blood work is advised
...

Dyslipidemia is diagnosed by measuring serum lipids
...

Dyslipidemia is often diagnosed with routine screening tests
...
g
...
Physical findings are less common,
and suggest primary dyslipidemia
...

o Onset of premature atherosclerotic disease (men < 55 years, women < 60 years)
o Family history of premature atherosclerotic disease or severe hyperlipidemia
o Serum cholesterol > 190 mg/dL (> 4
...
Total cholesterol and triglyceride values reflect cholesterol and triglycerides in all circulating
lipoproteins, including chylomicrons, very low density lipoprotein, intermediate-density lipoprotein
(idl), low density lipoprotein, and high density lipoprotein
...

Total cholesterol and high density lipoprotein-cholesterol may be measured in the non- fasting state,
but most patients should have all lipids measured while fasting (usually for 12 hours) for maximum
accuracy and consistency
...
Also, lipid profiles can vary
for about 30 days after an acute myocardial infarction (MI); however, results obtained within 24

hours after MI are usually reliable enough to guide initial lipid-lowering therapy
...
Very low density lipoprotein is estimated by
triglyceride ÷ 5 because the cholesterol concentration in very low density lipoprotein particles is
usually one fifth of the total lipid in the particle
...
Lifestyle changes example exercise, dietary modification
2
...

3
...

The main goal for dyslipidemia treatment is the prevention of atherosclerotic cardiovascular disease,
including acute coronary syndromes, stroke, transient ischemic attack, or peripheral arterial disease
presumed to be caused by atherosclerosis
...




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