Biochem Diseases

Front 1

Friedwald Equation-purpose

Back 1

Screening with lipid panel--LDL

Front 2

Friedwald Equation

Back 2

LDL = Total chol. - TAG/5 - HDL (HDL is measured from supernatant

Front 3

Ratio of VLDL to VLDL-TAG

Only valid if (2)

Back 3

1:5 (VLDL is estimated to be 20% of total TAG)
***Only valid if (1) taken 12hrs after fasting (2) total TAG <300mg/dL

Front 4

Hyperlipidemias

Classification

Back 4

Disorders in synth/clearing of lipoproteins

Fredrickson Classification-->NO DIAGNOSTICS, JUST CLASSIFIES

Front 5

3 Important Classes of Hyperlipidemias

Back 5

1. Isolated Hypercholesterolemia = (IIa) ^LDL only

2. Isolated hypertriglyceridemia = (IV) ^VLDL; (I) ^ CM

3. Combined Hyperlipidemas = (2b) ^ LDL and VLDL; (III) ^CM and IDL; (V) ^CM and VLDL

Front 6

Familial Hypercholesteremia (Type ___) Class_____

Back 6

Type IIa --> Isolated Hyperlipidemia (LDL only)

Front 7

Familial Hypercholesteremia
a. inheritance
b. increase in
c. incidence

Back 7

a. autosomal dominant; LDL receptor mutation
b. marked increase in LDL: elevated C but NORMAL TAG
c. Homozygous rare, Heterozygous common, French Canadians

Front 8

Familial Hypercholesteremia
a. Clinical signs i. homozygous ii. heterozygous
b. Complications
c. Tx.

Back 8

ai. cutaneous xanthomata (extremities/butt)
aii. TENDON xanthomata (75% of pt.), Corneal arcus (accumulation of cholesterol leads to opaque cornea)
b.i. accel atherosclerosis and early death (5-6 yrs)
b.ii. Coronary atherosclerosis (50% chance MI by 60yrs)
c.i. Aggressive combination therapy (statins, absorption inhib., niacin); LDL aphresis
c.ii. Reduced dietary fat/cholest; Combination therapy

Front 9

Familial Hypertriglyceridemia (Type ______)

Class

Incidence/inheritance

Back 9

Type IV

Class-->Isolated Hypertriglyceridemia

Common (1:300)
Dominant

Front 10

Familial Hypertriglyceridemia
i.Primary Cause
ii. Secondary cause

Back 10

i. increased VLDL production and/or decreased VLDL catabolism

ii. increased VLDL synthesis from increased carb intake, obesity, insulin resistance, alcohol, estrogen use
*obesity/insulin resistance also decreases LDL concentration

Front 11

Familial Hypertriglyceridemia
i. Serum appearance
ii. cholesterol levels

Back 11

i. opaque serum appearance
ii. [Cholesterol] normal to 20% increase (<250 mg/dL)

Front 12

Familial Hypertriglyceridemia
i. Complications
ii. Tx

Back 12

i. assymptoatic but increased risk of CVD
ii. treat the 2º causes (increased carbs, obesity, insulin resist., alcohol...) then treat the hyperlipidemia

Front 13

Familial Chylomicronemia Syndrome (Type ___)

Class

Incidence/inheritance

Back 13

Type I

Isolated hypertriglyceridemia

Very Rare (a:1,000,000)

Dominant

Front 14

Familial Chylomicronemia
i. Primary Inherited causes

ii. lab results (test tube)

Back 14

i. LPL synthesis deficiency
ApoC-II deficiency

ii. elevated TAG-->FASTING:
fasting plasma-->milky with CM-creamy top

Front 15

Familial Chylomicronemia
i. cholesterol levels
ii. CM levels
iii. VLDL levels

Back 15

i. cholesterol normal
ii. CM elevated
iii. VLDL elvated (need Apo-CII)

Front 16

Familial Chylomicronemia
Symptoms (4)

Back 16

1. eruptive xanthomata (fat plaque on skin)
2. HepatoSPLENomegaly (from CM uptake)
3. Childhood pancreatitis
4. NO premature CVD or atherosclerosis

Front 17

Familial Chylomicronemia
Therapy

Back 17

Limit dietary fat (15g/day) + fat soluble vitamin supplements.

*diet with SHORT AND MEDIUM chain FA (absorbed into blood stream w/o CM/VLDL)

Front 18

Familial Combined Hypertriglyceridemia (Type___)

Class

Incidence/inheritance

Back 18

Type IIb

Combined hypertriglyc.

MOST COMMON INHERITED LIPID DISORDER (1:200)
-->20% pt >60yrs with CVD have type IIb

Front 19

Familial Combined Hypertriglyceridemia

i. Primary Cause

Back 19

i. almost always caused by overproduction of Apo B-100 (VLDL overproduction)

other contributers are obesity, glucose intolerance, insulin resistance, hypertension

Front 20

Signs

Back 20

NO xanthomatas

High risk of premature CVD

Front 21

Tx

Back 21

AGGRESSIVE-->diet, weight loss, statins (HMG CoA mimicks) and niacins

Front 22

Familial Dysbetalipoproteinemia (FDBL, Type ___)

Class

Incidence

Back 22

Type III (FDBL)

Combined Hypertriglyceridemia

Rare (1:10,000)

Front 23

Familial Dysbetalipoproteinemia
Cause

Homozygous ___

Back 23

polymorphism of Apo-E gene causes one allele (Apo-E2) to bind poorly to the liver so LDL, IDL, and CM remnants bind poorly

Homozygous E2/E2-->.5% of population (.5% of this population develops FDBL)

Front 24

Familial Dysbetalipoproteinemia

Secondary factors

Back 24

high-fat, diabetes melitus, obesity, hypothyroidism, estrogen deficiency (menopause), alcohol

Front 25

Familial Dysbetalipoproteinemia

TAG levels
Cholesterol levels
VLDL and IDL levels

Back 25

TAG elevated
Total C elevated
VLDL/IDL elevated

Front 26

Symptoms

Back 26

Symtoms: palmar xanthoma, premature coronary and vascular diseases

Tx: First correct precipitating factors (i.e. obesity) then treat primary cause (polymorphism of ApoE)

Front 27

Type I
i. lipoprotein
ii. TG
iii. Cholesterol
iv. LDL
v. HDL
vi. Plama
vii. Xanthomas
viii. Pacreatitis
ix. Coronary AS
x. Peripheral AS
xi. Molecular defects

Back 27

Chylomicronemia
i. lipoprotein CM
ii. TG ++++
iii. Cholesterol +
iv. LDL Low
v. HDL +++
vi. Plama Lactescent (milky)
vii. Xanthomas eruptive
viii. Pacreatitis PRESENT
ix. Coronary AS NO
x. Peripheral AS NO
xi. Molecular defects LPL and ApoC-II

Front 28

Type IIa
i. lipoprotein
ii. TG
iii. Cholesterol
iv. LDL
v. HDL
vi. Plama
vii. Xanthomas
viii. Pacreatitis
ix. Coronary AS
x. Peripheral AS
xi. Molecular defects

Back 28

i. lipoprotein
ii. TG
iii. Cholesterol
iv. LDL
v. HDL
vi. Plama
vii. Xanthomas
viii. Pacreatitis
ix. Coronary AS
x. Peripheral AS
xi. Molecular defects

Front 29

Abetalipoproteinemia (type)

Back 29

CM retention disease

autosomal RECESSIVE

Rare (1:1,000,000)

Front 30

Abetalipoproteinemia
Cause

Back 30

Gene that codes for Microsomal Transfer Protein that transfer lipids to nascent VLDL and CM before they're released from liver(hepatocytes) and inestines(enterocytes)

Front 31

Abetalipoproteinemia
Effects

Back 31

Decreased total cholesterol and decresed TAG

CM VLDL LDL almost absent from plasma

Front 32

Abetalipoproteinemia Symptoms

Back 32

Failure to thrive, diarrhea, neurologic-->mainly due to fat malabsorption and lipid soluble; lipid accumulation in enetrocytes...diarrhea?

Front 33

Abetalipoproteinemia
Tx

Back 33

Low-fat/calorie diet, high doses of vitamins

Front 34

Tangier Disease
i. Inheritance
ii. incidence
iii. defect

Back 34

Autosomal Recessive

Very Rare

Defect in ABC-A1 protein

Front 35

Tangier Disease

Effect of defect

Back 35

ABC-A1 prevents transfer of cholesteral from pereferal cells to HDL...HDL3 can't mature to HDL2 and transport to VLDL

Front 36

Tangier Disease

Symptoms (2)

Back 36

1. low HDL levels (<5mg/dL)...b/c HDL is rapidly excreted from plasma
2. Hepatosplenomegaly

3. Enlarged tonsils

4. intermittent neuropathy (peripheral nerve defect) due to CM accumulation--->No Apo-E b/c low HDL

Front 37

Tangier Disease

Association with macrophages

Back 37

increased uptake of LDL by macrophages-->leads to fatty smears

Front 38

Tangier Disease

Risks

Back 38

CVD but not extreme