Download MBBS Biochemistry PPT 73 Dyslipoproteinemias And Fatty Liver Lecture Notes

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