Lipoprotein

VLDL:

Synthesized inLiver.
Mostly composed of TG.

Lipid 90-93%

Function:
Transport TG from liver to peripheral tissue.

Metabolism :
Extrahepatic tissue by lipoprotein lipase

Metabolic end product:
FFA
Glycerol
IDL/VLDL remnent

Fate:
Taken by liver
converted to LDL

LDL:

Composed of 79% lipid
Protein 21%

Contains cholesterol and cholesterol ester.

Derived from VLDL in the plasma

Chief pathogenic factor for atherosclerosis.

Functions:
Provides cholesterol to peripheral tissues.

Metabolism:
30% extrahepatic tissue
70% inside liver.

HDL:

Lipid 33%
Protein 67%

Synthesized inside the liver.

Function:
Transport Cholesterol from peripheral tissue to liver.

Usually biconcave shape. When it picks up cholesterol it become round.

Transfer cholesterol to VLDL,LDL in exchange of TAG/TG
carry CE(ester) to liver
Remove free cholesterol from extrahepatic tissue by LCAT(lecithin cholesterol actyl transferase)

Lipoprotein

Protein part of lipoprotein is called apo protein.

Types of lipoprotein:
1. Chylomicron
2.VLDL(very low density lipoprotein)
3.LDL
4.HDL

Here one should be noted density will decrease if lipid amount increase.
So in VLDL, lipid is much more than in HDL

another matter;
Increase protein causes the increase elecrophoric mobility.


Basics of apoprotein:
maintenance the shape of liupoprotein.
B100. the apoprotein which synthesize by B gene 100%
B48... B gene synthesize 48% of the protein.


metabolism of Lipoprotein:

Chylomicron:
Site of synthesis: Small intestine.
Size 100 nano m
Low density
combines with C1,11,111 E in circulation.

lipid 98-99%
Protein 1%

Functions:
Transport dietary TG,Cholesterol,Cholesterol Ester from instestine to peripheral
tissue.

Metabolism:
Extrahepatic tissue by lipoprotein lipase.

Metabolic end product:
FFA
Glycerol
Chylomicron remnant(Removed by liver )

Metabolism of TG/Triacyl glycerol

TG is consit of three molecule of fatty acid esterified into glycerol.

Storage:

Main storage: Adipose cell. Most of TG deposite as droplet.
Other store: Liver and muscle cell, Store small amount of TG.

Fate of TG:

1. Fate of Adipose tissue TG:
Store in cytosol as depot fat.
Ready to mobilize when body require fuel.
2. Liver: TG is packed with cholesterol, Cholesterol ester
Phospholopid ,protein forms various lipoprotein.

Biosynthesis:
Site : liver and adipose tissue.

Source : FFA.(free fatty acid)

Lipolysis of TG:

hydrolysis of TG is called lipolysis.

Enzyme required:
Lipase.
a. In adipose tissue: Hormone sensitive lipase.
b. In vessles. Lipoprotein lipase(chylomicron, VLDL)

hormone sensitive lipase
TG......................................................>>>DAG(diacylglycerol)+FFA


DAG....................................................>>>MAG+FFA

MAG..................................................>>>Glycerol+FFA

So the products of lipolysis are:
a. FFA
b.Glycerol

Fate of Glycerol:
a.In adipose tisssue..Can not utilize glycerol as there is no enzyme to metabolise
So glycerol is the excellent index of glycolysis in adipose tissue.
b.In liver. glycerol is converted to glycerol phosphate by glycerol kinase.

Absorption of lipid

Primary product of lipid degradation are:
a. FFA
b.2-monoglycerol
c.Cholesterol.

Absorption:

Site of absorption:
Brush border of intestinal mucosal cell.

process of absorption:

Short and Medium chain fatty acid absorbs into directly into portal vein
Long chain fatty acid and 2-monoglycerol absorbs by brush border forming micelle.

Composition of Dietary lipid

TG
Sterol(Cholesterol)
Sterol Ester
Phospholipid

Fat.... Are all triester of tri hydric alcohol , glycerol and various fatty acid.

Lipid and Lipid disorder.

Lipid classsification:

1. Simple lipid: (fatty acid with various alcohol)
a. Neutral fat
Fatty acid+Glycerol= TG
b. Wax
Fatty acid + High molecular wt alcohol

2.Compound Lipids:(Fatty acid +alcohol+others)

a. Phospholipids
Fatty acid+Glycerol+Phosphoric acid
b.Glycolipid
Lipid+CHO+Nitrogenous Base
c.Sulpholipid
Lipid+sulphergroup
d.lipoprotein
Lipid+Plasma protein

3. Derived lipid
Saturated and Unsaturated fatty acid
glycerol
sterol
vit A, Vit D

4.Miscelleneous Lipid.
Aliphatic hydrocarbon
carotinoid
Vit e, Vit K

Myelodysplastic syndrome

The word dysplasia is premalignant condition. Any dysplasia is premalignant.It is premalignant so malignancy of myeloid origin may occur. That is it may turn into leukaemia whether acute or chronic.

Here bone marrow dysplasia occur so cytopenia occurs. So we can call MDS as a group of disorder where .

the word.

Myelo means Blood cells.

Dysplasia means abnormal growth.

Here below the classification of MDS:

French American British (FAB) Classification System
Even though the newer WHO system updated the FAB system, the FAB system is still used by some doctors today.

The FAB system is based on four main factors:

* The percentage of blast cells in the bone marrow
* The percentage of peripheral blood blasts
* The percentage of red blood cell precursors with abnormal iron deposits called ring sideroblasts
* The percentage of monocytes in the blood

The FAB system divides MDS into 5 subtypes. These subtypes include:

1. Refractory anemia, also called RA
2. Refractory anemia with ring sideroblasts, also called RARS
3. Refractory anemia with excess blasts, also called RAEB
4. Refractory anemia with excess blasts in transition, also called RAEB-t
5. Chronic Myelomonocytic Leukemia, or CMML

Diagnosis:
BME: cytopenia with dysplastic feature.Hypercelluler marrow.
Blast cell must not more than 30 %. defect in chromosom 5/7

Management:
Treatment is unsatisfactory. Blood transfusion with antibiotics.
Agressive antileukaemic therapy is not effective.
Retenoic acid is not fulfilling the promise.
Low dose cytosin arabinose has little effect
ABMT has 30% success .

International Prognostic Scoring System (IPSS)

The IPSS gives each patient a score to help their doctor understand how quickly their MDS is progressing and what is likely to happen to their disease over time. The score is based on several factors that are linked to MDS. They are:

• Percentage of blasts in the bone marrow
• Changes in cell chromosomes, also called cytogenetics
• Low blood cell counts or cytopenias
  

Each factor gets a score. Together, the scores tell which risk groups you fall into.

Your IPSS score helps your doctor to answer the following questions:

• How severe is your case of MDS?
• How likely is your case to become acute myeloid leukemia or AML if treated only with supportive care?
• How long are you likely to live if you are treated only with supportive care?

Factor	Value	IPSS Score
Blasts in bone marrow	less than 5% 5% to 10% 11% - 20% 21% - 30%	0 0.5 1.5 2.0
Cell DNA changes (cytogenics)	Good Intermediate Poor	0 0.5 2.0
Low blood counts or cytopenias	0 or 1 cytopenia 2 or 3 cytopenias	0 0.5

Using the IPSS, a patient is given a score between 0 and 3.0. A patient can be put into one of four risk groups, two lower-risk and two higher-risk. Scores of less than 1.5 are considered lower-risk.

This score tells you what risk group you fall into. For example:

• If your IPSS score is 0, you are in the low-risk group
• If your IPSS score is 0.5 to 1, you are in the intermediate-1 risk group
• If your IPSS score is 1.5 to 2, you are in the intermediate-2 risk group
  
• If your IPSS score is more than 2.0, you are in the high-risk group

Learn about Treatments for MDS.

__________________________

Order an AA&MDSIF information packet containing detailed information about MDS and its treatment.

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Prognosis:
First two is chronic disorder so less agressive.
Last three is agressive.