Download MBBS (Bachelor of Medicine, Bachelor of Surgery) 1st year (First Year) Biochemistry ppt lectures Topic 73 Dyslipoproteinemias And Fatty Liver Notes. - biochemistry notes pdf, biochemistry mbbs 1st year notes pdf, biochemistry mbbs notes pdf, biochemistry lecture notes, paramedical biochemistry notes, medical biochemistry pdf, biochemistry lecture notes 2022 ppt, biochemistry pdf.
Lipid Associated Disorders
OR
Lipid Related Clinical Problems
? Obesity- Metabolic Syndrome
? Dyslipoproteinemias/Dyslipidemias
? Fatty Liver
? Atherosclerosis
? Coronary Heart Diseases
? Myocardial Infarction
? Stroke
Causes of Lipid Associated Disorders
? Diseases associated with abnormal lipid
concentrations may be due to:
?Nutritional Imbalances
?Lifestyle habits
?Genetic abnormalities
?Secondary causes as a consequence of
other disease
Disorders Of Lipoproteins
Dyslipoproteinemias/Dyslipidemias
Types Of Lipoprotein Disorders
Hyperlipoproteinemias
And
Hypolipoproteinemias
Dyslipoproteinemias/ Dyslipidemias
? Dyslipoproteinemias can be subdivided
into two major categories
1. Hyperlipoproteinemias
? Hypercholesterolemia
? Hypertriglyceridemia
? Combined Hyperlipoproteinemia
2. Hypolipoproteinemias
Hyperlipoproteinemia
? Hyperlipoproteinemia is an
abnormal condition
? With an increased abnormal
levels of circulating
Lipoproteins in blood.
Dyslipidemias
? Dyslipidemias are due to defect in
Lipoprotein metabolism
? May include both excess and deficiency
of Lipoproteins.
? Associated mostly in increase of one or
more Lipid forms in blood circulation.
Classification Of
Dyslipidemias
Based On
Number Of Gene Involvement
Primary Hyperlipoproteinemia
?Monogenic defect
?Polygenic Defect
Monogenic Disorders
vFamilial Hypercholesterolemia
vHomozygous or Heterozygous
vDefect: inactive LDL receptor
vFamilial Lipoprotein Lipase deficiency
vDefect: inactive lipoprotein lipase
vFamilial combined Hyperlipidemia
vDefect: Unknown
Polygenic/Multifactorial
? These are commonly
encountered
vHypercholesterolemia
vHypertriglyceridemia
Causes Of Dyslipoproteinemias/
Dyslipidemias
? Dyslipidemias are generally caused by
impaired Lipoprotein metabolism :
?Biosynthesis (Increased)
?Transformation and Transport (Improper )
?Uptake and Utilization (Decreased)
Causes of Hyperlipoproteinemia
? Increased formation of Lipoprotein
? Reduced clearance of LP from circulation
? Factors Causing These
? Excessive dietary intake of Carbs and Lipids
? Biochemical defects in LP metabolism
? Deficient Protein to form Apoproteins
? Defect in Enzymes and Proteins Associated to LP
? Defect in Receptors for LP
? Use of drugs that perturb LP formation or
catabolism
Secondary Causes Of Dyslipidemias
Types of
Hyperlipoproteinemias
Fredrickson Classification
of
Hyperlipoproteinemia
Type I
Lipoprotein Lipase Deficiency
Increased Chylomicrons and
Hyperlipoproteinemia VLDL
Hypertriglyceridemia
Type II a Defect in LDL Receptors
Increased LDL levels in blood
Hyperlipoproteinemia Hyperbetalipoproteinemia
Hypercholesterolemia
Type II b Increased production of Apo B
Increased production of
Hyperlipoproteinemia VLDL and impaired LDL
catabolism Increased VLDL and
LDL
Type I I
Defect in ApoE
Familial Dysbeta Broad Beta Disease
Lipoproteinemias Increased IDL
Type IV
Impaired VLDL metabolism.
Increased VLDL
Hyper-pre-b-
Lipoproteinemia
Due to acquired conditions viz
q Obesity
q Alcoholism
q Diabetes mel itus
Increased VLDL and
Chylomicrons
Due to acquired
Type V conditions viz
q Obesity
Combined
q Alcoholism
Hyperlipoproteinemia
q Diabetes mel itus
Deficiency Of Lipoprotein Lipase
Leads To
Familial Type I Hyperlipoproteinemia
? Defect in Lipoprotein Lipase activity
? Does not clear circulating
Chylomicrons and VLDL;
? Increases levels of circulating
Chylomicrons and VLDL
? Associated Hypertriglyceridemia
? This is termed as Familial Type I
Hyperlipoproteinemia.
Type I Hyperlipoproteinemias
? Shows a dramatic accumulation (1000
mg/dl) of Chylomicrons and VLDL in
plasma
? Usual y associated with
acute abdomen pain due
to acute pancreatitis
? plasma TAG even in the
fasted state
Type I I Hyperlipoproteinemia
? Familial dysbetalipoproteinemia
? Due to Apo E deficiency
? Associated with
Hypercholesterolemia &
premature Atherosclerosis
Hypolipoproteinemias
Hypolipoproteinemias
? Hypolipoproteinemias are
abnormal conditions
? With decreased levels of
circulating Lipoproteins in
blood.
Conditions Of Hypolipoproteinemias
? Decreased synthesis of
Lipoproteins
? Deficiency of Lipotropic factors
required for Lipoprotein
biosynthesis.
Types Of Hypolipoproteinemias
Familial Hypobetalipoproteinemia
?Impairment in synthesis
of Apo B
?Characterized with low
LDL levels.
Abeta Lipoproteinemia
? Rare disorder
? No synthesis of Apo B (Total
Absence)
? Absence of LDL (Beta Lipoprotein) in
blood circulation
? Defect in TAG-transfer protein
? Accumulation of TAG in liver
Familial Alpha Lipoprotein Deficiency
Tangiers Disease
? Absence of HDL (Alpha Lipoprotein)
in blood
? Affects severely Reverse transport
of Cholesterol
? Hypercholesterolemia
? Increased risk of Atherosclerosis and
its Complications.
Combined Hyperlipoproteinemia
? Presence of elevated levels of both serum
Total Cholesterol and Triacylglycerols.
? Genetic form of this condition
?Familial Combined Hyperlipoproteinemia
(FCH)
?Type V Hyperlipoproteinemia
? An accumulation of Cholesterol-rich VLDL
and Chylomicron remnants as a result of
defective catabolism of those particles
38
Diagnosis And Therapeutic
Strategy Of Dyslipidemias
A. Identify patients at risk
1. Routine screening of Serum Lipid
profile
2. Assessment of contributing risk factors
B. Non-Pharmacologic therapy
1. Diet modification
2. Lifestyle modification
C. Pharmacologic therapy
? Lipids and lipoproteins are
important indicators of CHD risk,
? This is major reason for their
measurement in research, as well
as in clinical practice.
Lipid Profile and Lipoprotein Analyses
Estimation Of Lipid Profile
? Serum Triacylglycerol
? Serum Total Cholesterol
? Serum VLDL
? Serum LDL Cholesterol
? Serum HDL Cholesterol
Hypertriglyceridemia
? Serum Triacylglycerol
? Borderline = 150-200 mg/ dl
? High 200-500 mg/dl
? Very High > 500 mg/dl
? Familial Hypertriglyceridemia
? Genetic
? Secondary Hypertriglyceridemia
? Hormonal imbalances
? Imbalance between synthesis and clearance of VLDL
44
Hypertriglyceridemia
? Generally caused by deficiency of LPL or
LPL cofactor.
? LPL hydrolyzes TAG in Chylomicrons and
VLDL
? Deficiency of LPL prevents processing and
clearing of Lipoproteins.
? Elevated even with fasting condition.
45
Hypercholesterolemia
? Familial Hypercholesterolemia (FH)
?Homozygous rare 1/million
?Total cholesterol 800-1000 mg/dl
?Heart attack as early as teenage years
?Heterozygous cholesterols 300-600
mg/dl
?Heart attacks 20-50 years
Hypercholesterolemia
? Familial hypercholesterolemia (FH)
?Primarily LDL elevations
?Synthesis is normal but decrease or lack
LDL receptors
?Therefore LDL builds-up in serum
?Since cells cannot acquire from LDL
increase internal synthesis
LDL Methods
? Friedewald Calculation
? VLDL is estimated as TAG/5
LDL = Total Cholesterol ? HDL ? TAG/5
Lipoprotein Assay Methods
? Separate Lipoprotein Fractions By:
? Electrophoresis ? Agarose or Polyacrylamide
? Chromatographic
? Precipitation
? Ultracentrifugation
? Immunochemical
Serum Triglycerides
Normal
? Less than 150 mg/dL
Borderline High
? 150-199 mg/dL
High
? 200-499 mg/dL
Very High
? 500+ mg/dL
Serum Total Cholesterol
Normal
?Less than 200 mg/dL
Borderline High
?200-239 mg/dL
High
?240 mg/dL or higher
HDL Cholesterol
Optimal:
?60+ mg/dL for both males and females
At Risk for Heart Disease:
?Women: less than 50 mg/dL
?Men: less than 40 mg/dL
LDL Cholesterol
Optimal
? Less than 100 mg/dL
Near or above Optimal
? 100-129 mg/dL
Borderline High
?130-159 mg/dL
High
?160-189 mg/dL
Very High
? 190+ mg/dL
?Cholesterol Levels of:
?Healthy person = < 200 mg/dl
?Heterozygous individuals = 300 mg/dl
?Homozygous individuals = 680 mg/dl
Consequences Of
Dyslipoprotein Metabolism
?Fish Eye Disease
?Fatty Liver
?Atherosclerosis and
its Complications
Fish Eye Disease
Fatty Liver
Role Of Liver In Lipid Metabolism
? Liver is the Biochemical Factory of
Human Body.
? Liver plays an important role in
Lipid metabolism.
? Major pathways of Lipid
metabolism are efficiently carried
out in Liver.
Lipid Metabolism
At Liver
In Well Fed Condition
? Liver in well fed condition efficiently carries
out various metabolic pathways of Lipid
Metabolism.
?De Novo biosynthesis of Fatty acids
?Triacylglycerol Biosynthesis
?Cholesterol Biosynthesis
?Phospholipid Biosynthesis
?Glycolipid Biosynthesis
?VLDL Biosynthesis
Lipid Metabolism
At Liver
In Emergency Condition
? Liver in emergency condition carries
following metabolic pathways of
Lipid metabolism efficiently:
?Beta Oxidation of Fatty acids
?Ketogenesis
?Bile Acid and Bile Salt Formation
? Though Liver is predominant site
for Lipid biosynthesis.
? Liver is not the storage organ for
Lipids.
?Normally 3-5% of Lipids are
present in Hepatocytes.
? Endogenously biosynthesized
Lipids in Liver are
? Mobilized out in the form of
VLDL molecule.
? Efficient formation of VLDL
in Liver
? Does not al ow the excess
of Lipids to remain in Liver
tissue.
Fatty Liver/
Fatty Liver Disease/
Hepatosteatosis
What Is Fatty Liver?
? Fatty Liver is an abnormal
condition
? Where there is more than 5% of
Lipids retained in Hepatocytes.
What Is Fatty Liver Disease?
? Fatty Liver disease (FLD), is a reversible
condition of Liver
? Wherein large vacuoles of Lipids
accumulate in Liver cel s
? Via the process of Steatosis (Abnormal
retention of Lipids within a cell)
What Is Steatohepatitis ?
? Progressive inflammation of
Liver (Hepatitis),
? Due to abnormal accumulation of
Lipids(Steatosis) is termed as
Hepatosteatosis/Steatohepatitis
.
Causes Of Fatty Liver
Clinical Conditions
Leading To Fatty Liver
OR
Risks For Developing Fatty Liver
?Defect in Hepatic
?Biosynthesis of Lipids
?No Mobilization of
Endogenously
biosynthesized Lipids in
Liver
?Accumulates Lipids in Liver
? Increased biosynthesis of Lipids than
the mobilization capacity ,due to
increased Carbohydrates.
? Decreased mobilization of Lipids
from Liver cells due to decreased
VLDL formation.
?Deficiency of Lipotropic
factors affects
?The VLDL formation and
mobilization of Lipids
out of Hepatocytes.
Conditions Leading To Fatty Liver
? Metabolic Syndrome
?Obesity
?Hypertension
?Dyslipidemias
?Diabetes mel itus
? Alcoholism
? Malnutrition
(Deficiency of Lipotropic Factors)
? Wilsons Disease
? Hepatitis A
? Hepatitis C
? Hepatotoxic Drugs : MTX, VA,
Acetaminophen, TC, Tamoxifen,
Nefidepine, Amiodarone, CCl4 etc
Lipotropic Factors and Their Role
Adequate Presence of
Lipotropic factor
Prevents Retention of Lipids
in Liver
There by preventing Fatty Liver.
? Lipotropic Factors are chemical
substances which helps in
formation of Phospholipids.
? This in turn helps in proper
formation and mobilization of
VLDL out from Liver.
Names Of Lipotropic Factors
? Lipotropic Factors are chemicals
involved in biosynthesis of
Phospholipids:
?Choline
?Betaine forms Choline
?Inositol
Amino Acids As Lipotropic Agents
?Glycine
?Serine
?Methionine
Vitamins As Lipotropic Factors
?Vitamin B 12
?Folic Acid
Types Of Fatty Liver
4 Types Of Fatty Liver
? Alcoholic Fatty Liver
? Non Alcoholic Fatty Liver Disease (NAFLD)
? Non Alcoholic Steatohepatitis (NASH)
? Acute Fatty Liver of Pregnancy
Consequences Of Fatty Liver
? Fatty liver is a reversible condition
and usual y goes away on its own.
? Generally Fatty liver often has no
symptoms and
? Does not cause any permanent
damage.
Consequences Of Fatty Liver
? Constant accumulation of
abnormal excess amount of
Lipids in Hepatocytes
? Affects the normal Liver
functions
? Leads to Parenchymal damage
to Liver Tissues
? Causes Liver Cirrhosis.
? Excess of Lipids deposition in Hepatocytes
? Interferes the biochemical functions
? Brings inflammation of Liver (Hepatitis)
? Changes the cytological features
? Damages the cell components
? Causes Liver Fibrosis
? Leads to Liver Cirrhosis
? Liver Carcinoma
Natural History of Fatty Liver Disease
Fatty liver
Steatohepatitis
Steatohepatitis + Fibrosis (First Stage of Scar)
Steatohepatitis + Cirrhosis
Cryptogenic Cirrhosis
When there is repeated damage to
the Liver
Permanent scarring of Hepatocytes
takes place
This is cal ed Liver Cirrhosis
Diagnostic Features
OF
Fatty Liver Disease
Laboratory Abnormalities
In Fatty Liver Disease
? 2 - 4 fold ALT &
? Normal Albumin. PT
AST
? Low ANA + < 1 in 320
? AST: ALT Ratio < 1
? Serum Ferritin
? ALP slight in 1/3
? Iron saturation
? Dyslipidemia - TAG ? AST: ALT Ratio > 1
? FBG and PPBG
if Cirrhosis sets in
? BUN & Creatinine - N
Fatty liver Normal liver
This post was last modified on 05 April 2022