lipid lab

Question 1

1. After finding high lipid concentrations in the serum, what tests would you
   employ to confirm or exclude the secondary causes of hyperlipidemia?

Answer 1

1) Obesity/Metabolic Syndrome - more FFA → more liver TAGs → ↑ VLDL → ↑ LDL ↓ HDL
I can measure waist circumference, BMI, fasting glucose, BP, TAGs + HDL

2) DM - ketone/FFA efflux from adipose → liver TAGs + VLDL → ↑ LDL / ↓ HDL
-> I can perform the WHO diagnostic algorithm (random glucose → fasting glucose → OGTT)
->type I pt only develops dyslipidemia if untreated;
-> type II usually has dyslipidemia
in type II, LPL activity ↓ so chylomicrons + VLDL ↑

3) Hypothyroidism - synthesis + activity of LDL-R ↓ → serum IDL/LDL ↑
- > check TSH, T3, T4.

4) Kidney Disease - proteinuria → hypoalbuminemia → ↑ protein synth (thus apoproteins) → lipids ↑

I can measure albumin, protein content of urine.

• > in kidney transplant, immunosuppression glucocorticoids → ↑ lipids
  5) Cholestasis - see ↑ “Lipoprotein X” (LP-X) an abnormal low density lipoprotein

6) Hepatic Disease - primary biliary cirrhosis + obstructive liver diseases → ↑ cholesterol
I can measure ASAT, ALAT, albumin and GGT.
LP-X also seen

7) Cushing - ↑ glucocorticoids → ↑ VLDL synthesis → ↑ serum LDL (mild)
measure serum cortisol

8) Alcoholism - ↓ NAD+ → ↓ β-oxidation → ↑ TAG synthesis
I can measure GGT moderate alcohol intake inhibits CETP → ↑ HDL

9) Glycogen Storage Disease -
↓ G-6-phosphatase (von Gierke) → adipose FFA efflux ↑ → TAG synthesis ↑

10) Estrogen Treatment/Pregnancy - ↑ VLDL synth and ↓ hepatic lipase activity → ↑ TG/Chol.
should only be treated with diet

Question 2

2. The laboratory parameters of a male person having normal blood pressure, BMI 23 kg/m2 are:
   serum TG: 1.5 mmol/l
   serum LDL cholesterol:4.4 mmol/l
   serum CRP: 5 mg/l
   What is the risk of CHD for this person? What are the risk factors of atherosclerosis?

Answer 2

TGs and BMI are normal
LDL is high (>3.4 mmol/l)
CRP is within normal range, but still above the 3.0 mg/L cut-off for high risk of CHD development
Because of higher CRP and high LDL, patient is at high risk for developing CHD.

Atherosclerosis Risk Factors:
Modifiable: smoking, exercise, hypertension, weight, diet, stress
Non-modifiable: age, sex, genetics, diseases (DM, renal disease … can be treated but not cured)

Question 3

3. A 45 year old man has the following parameters:
   waist circumference: 110 cm
   BP: 140/90 mmHg
   HDLC: 0.9 mmol/l
   fasting blood glucose: 6.3 mmol/l
   What is your opinion about the risk of CHD for this person?

Answer 3

waist large (>102 cm), BP high, HDL low (<1.0 mM), glucose high (btwn 6-7 needs OGTT)
patient is at high risk for CHD
and meets 4 of the criteria for metabolic syndrome (waist, BP, HDL + glucose)
other metabolic syndrome criteria = high TAGs

Reference:
not related so much
Metabolic Syndrome is not a disease, but rather a cluster of disorders of your body’s metabolism, including:
o High blood pressure
o High insulin levels
o Excess body weight
o Abnormal cholesterol levels

 Each of these disorders is by itself a risk factor for other diseases.
 In combination, however, these disorders dramatically boost the chances of developing potentially life threatening
illnesses, such as diabetes type2, heart disease
or stroke.

3 out of 5 criteria
1.Waist circumference:
A. Men>102 cm (>40 in)
B. Women>88 cm (>35 in)

2. Triglycerides >1.7mmol/l (1.7mM)
3. HDL cholesterol:
   A. Men <1mmol/l (1mM)
   B. Women <1.3mmol/l (1.3mM)
4. Blood pressure 130/ 85 mm Hg
5. Fasting glucose >= 5.6mmol/l

Question 4

4. A 35 year old man wanted to be screened for possible ischemic heart disease
   because his father died early from a heart attack. The patient was not obese and was a nonsmoker. On examination his blood pressure was normal and the only abnormality was tendon xanthoma arising from the Achilles tendons.
   An ECG taken at rest was normal but ischemic changes developed on exercise. Fasting lipids: serum cholesterol 8.7 mmol/l, triglyceride 1.1 mmol/l. What is the most likely diagnosis and how can you confirm it?

Answer 4

High serum cholesterol (>5.2 mM) but normal TGs (< 1.7 mM) this is a “type IIa” phenotype hyperlipidemia, suggestive of familial hypercholesterolemia.

Diagnosis can be confirmed via genetic testing (LDL-R or Apo-B mutation), fibroblast culture (to count LDL-Rs on cell surface), or just differential diagnosis via serum lipids,
presence of xanthomas and familial tendency toward similar findings.

Heterozygotes for the autosomal dominant LDL-R mutation may have CHD as young adults, whereas homozygotes are at risk for childhood CHD + xanthomas.

Treatment with statins (HMG-CoA reductase inhibitors) is recommended.
ezetimbe etc.

Other symptoms of the disease include xanthelasma (cholesterol deposits in the skin below the eyelids), arcus senilis (cholesterol deposits in the corneal stroma).

The ischemic changes on excersie might already indicate stable angina.

Question 5

5. A middle-aged man saw his family doctor, because he got rashes. On examination he was found to have extensive yellowish papules, with an erythematous base, on his buttocks and elbows and orange-yellow discoloration of the palmar creases.
   Fasting lipids: serum cholesterol 7.6 mmol/l, triglyceride 8.1 mmol/l.
   What is your diagnosis?

Answer 5

High serum cholesterol (>5.2 mM) and very high TGs (>1.7 mM).
Discolored palmar crease = xanthoma striatum palmare

Lipid increase pattern + xanthomas indicative of familial type III hyperlipoproteinemia
due to an autosomal recessive Apo E mutation (a defective “ApoE2” form)
results in increased TGs and IDL00
also known as “familial dysbetalipoproteinemia” or “remnant hyperlipidemia” because of Apo E’s role in removal of VLDL remnants (IDL)

Can test for the mutated gene, must have two mutated alleles.
Xanthomas + atherosclerosis develop due to increased accumulation of cholesterol within scavenging macrophages