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Compendium Chemistry > Lipids and Carbohydrates > Flashcards

Lipids and Carbohydrates Flashcards

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1
Q

Review of lipids

  • Lipoproteins contain
  • Lipoprotein classes determined by, #
  • Lipid metabolism
A
  • Lipoprotein contain
    • cholesterol
    • TG
    • phospholipids
    • apolipoprotein
  • 5 different lipoprotein classes based on proportions of above constituents
  • Ingested lipids are internalized by small bowel enterocytes and packaged into chylomicrons
  • Chylomicrons transport lipid from enterocytes to hepatocytes into which they are endocytosed via apolipoprotein E
  • In liver, cholesterol and TG undergo metabolism before being packaged into VLDL
  • VLDL is vehicle for transport into bloodstream
  • in blood the TGs in VLDL undergo hydrolysis by the endothelium bound lipoprotein (LPL) producing IDL and eventually LDL
  • LDL is vehicle for transporting cholesterol from bloodstream to somatic cells where LDL undergoes endocytosis mediated by LDL receptor and apolipoprotein B100
  • liver also produces HDL, a scavenger of cholesterol
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2
Q
A
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3
Q

Lipid measurements

  • directly measured lipids
  • how is LDL determined?
  • how is VLDL determined?
  • lipoprotein measurement performed how?
  • lipoprotein electrophoresis
  • gross characteristics of lipid specimen
A
  • Directly measured lipids:
    • total cholesterol
    • HDL
    • TG
  • LDL is calculated
  • VLDL cholesterol is estimated as TG/5 in mg/dL or TG/2.2 in mmol/L
    • invalid when
      • TG>400 mg/dL
      • chylomicrons present
      • beta VLDL characteristic from type III dyslipidemia
  • Ultracentrifugation is used for lipoprotein measurement in reference labs
  • lipoprotein electrophoresis:
    • chylomicrons do not move from point of application
    • LDL migrates to beta
    • VLDL migrates to preBeta
    • HDL migrates to alpha
  • Overnight refrigeration produces pattern
    • creamy layer on top of plasma indicates excess chylomicrons
    • turbidity or opacity of plasma indicates abundant VLDL
    • LDL and HDL even when present in excess do not visibly alter plasma
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4
Q

LDL calculation

A
  • Friedewald equation
  • not valid if
    • TG > 400
    • chylomicrons present
    • cholestasis
    • type III dyslipidemia
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5
Q

General features of lipid disorders

  • consequence of hyperlipidemia (LDL versus TG)
A
  • Increased LDL or IDL
    • Premature atherosclerosis
    • xanthelasma (yellow periorbital papules)
  • Increased TG (chylomicrons or VLDL)
    • eruptive xanthomas
    • acute pancreatitis, particularly when TG>500 mg/dL
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6
Q
A
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7
Q

Predominant hypercholesterolemia

  • cholesterol level
  • primary causes
  • secondary causes
A
  • Plasma total cholesterol exceeds 200 mg/dL
  • Usually related to elevated LDL
  • Most common primary cause of hypercholesterolemia is familial hypercholesterolemia (AD) - deficiency of LDL receptors or LDL receptor activity
  • Secondary causes of hypercholesterolemia:
    1. hypothyroidism
    2. diabetes mellitus
    3. nephrotic syndrome
    4. cholestasis
    5. cyclosporine
    6. thiazide diuretics
    7. loop diuretics
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8
Q

Predominant hyperTG

  • secondary causes
  • primary causes
A
  • Related to elevated chylomicrons or VLDL
  • Secondary causes
    1. heavy alcohol use
    2. obesity
    3. diabetes mellitus
    4. hepatitis
    5. pregnancy
    6. renal failure
    7. beta blockers
    8. isotretinoin
    9. corticosteroids
    10. nephrotic syndrome
    11. gout
  • Primary causes
    • familial combined hyperlipidemia
    • familial LPL deficiency
    • familial apo C II deficiency
    • familial hyperTG
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9
Q

Mixed hyperTG and hypercholesterolemia

A
  • most common in
    • severe diabetes
    • hypothyroidism
    • nephrotic syndrome
    • thiazides
    • loop diuretics
    • beta blockers
  • primary causes
    • familial combined hyperlipidemia
    • type III hyperlipidemia (dysbetalipoproteinemia)
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10
Q

Low levels of HDL cholesterol

A
  • HDL < 35 mg/dL
  • independent risk factor for premature atherosclerosis
  • Tangier disease:
    • autosomal recessive disorder
    • low cholesterol
    • normal to increased TG
    • absent HDL
    • absence of Apo A1
    • cholesterol esters deposit in the tonsils, lymph nodes, vasculature, and spleen
    • corneal opacities
  • secondary causes
    • smoking
    • obesity
    • sedentary lifestyle
    • anabolic steroids
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11
Q

Lipids in the assessment of coronary artery disease

  • major risk factors for CAD
  • testing
  • recommendations
A
  • Third Adult Treatment Panel report (ATP III) lists major risk factors for CAD:
    1. smoking
    2. HTN
    3. low HDL
    4. family history of premature CAD
    5. age >45 years for men and > 55 for women
  • ATP III recommends fasting lipoprotein profile (including total cholesterol (TC), LDL, HDL, and TG for all patients)
  • ATP III recommends specific cholesterol and LDL targets
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12
Q

ATP III cholesterol classification

A
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13
Q

ATP III Recommended LDL targets according to risk group

Notes

Target LDL

A
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14
Q

C peptide

  • C peptide: insulin
  • major clinical use of C peptide
  • what happens when blood is left in an unseparated test tube?
  • whole blood versus plasma glucose
  • how does glycosylated hemoglobin form?
A
  • C peptide: insulin is 5-15:1 when both are expressed in SI units: pmol/L
  • major clinical use of C peptide measurement is in detection of exogenous insulin administration
  • when blood is left in an unseparated test tube, glycolysis will reduce the glucose by 5-10 mg/dL/hour depending on temp and WBC count
    • sodium fluoride arrests this process for 24 hours
    • initial arrest of glycolysis takes 1-2 hours so there will be a 5-10 mg/dL decrement
  • uncalibrated whole blood glucose usually runs 10-15% lower than plasma glucose (depending on hct)
  • glycosylated hemoglobin is formed when hemoglobin undergoes nonenzymatic reaction with glucose
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15
Q

Glycosylated hemoglobin

A
  • HgbA1c is one type, normal is < 6%
  • HgbA1C depends on the concentration of serum glucose and the lifespan of the red cells (shortened red cell survival leads to relatively decreased HgbA1c)
  • HgbA1c is an indicator of glucose concentrations over the preceeding 3 months
  • HgbA1c can be translated into average blood glucose (AG) through the use of a formula:
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16
Q

Symptoms of hypoglycemia

A
  • Neuroglycopenic
    • related to reliance of brain upon glucose for metabolism, such that hypoglycemia directly leads to altered mental status
    • symptoms predominate in a fasting hypoglycemia in which the drop in serum glucose is moderate and gradual
  • Adrenergic
    • sweating
    • palpitations
    • tachycardia
    • nervousness
    • symptoms predominate in “reactive” hypoglycemia that tends to be more profound and rapid in onset
17
Q

Hypoglycemia differential diagnosis

A
18
Q

Drug induced hypoglycemia may be caused by

A

sulfonylureas (oral hypoglycemics)

alcohol

quinine

19
Q

Fasting hypoglycemia

  • pathophysiology

Insulinomas - presentation and pathology

A
  • Pathophsyiology
  • proliferation of islet Beta cells (nesidioblastosis or insulinoma)
  • inherited metabolic defects
  • sarcomas
  • endstage liver disease
  • Insulinomas are beta islet cell neoplasms resulting in high insulin levels
    • present with Whipple triad
      • hypoglycemic symptoms
      • plasma glucose < 45 mg/dL
      • relief of symptoms with glucose administration
20
Q

Reactive hypoglycemia

A
  • rapid onset hypoglycemia following a meal
  • causes
    • hereditary fructose intolerance
    • galactosemia
    • postvagotomy states (dumping syndrome)
    • early type 2 DM
21
Q

Type 1 DM

A
  • Autoimmune islet Beta cell destruction causing insulin deficiency
  • 5-10% of diabetics, most commoly presents in childhood
  • usually insulin dependent
  • autoantibodies
    • islet cell antibodies (ICA)
    • insulin autoantibodies (IAA)
    • antibodies to glutamic acid decarboxylase (GAD)
    • insulinoma associated protein (IA2, ICA512)
  • strong association with HLA DR and DQ loci with particular alleles having either predisposing or protective effects
22
Q

Type 2 diabetes

A
  • progressive insulin resistance
  • most common form of DM
  • adults
  • usually noninsulin dependent
23
Q

Gestational diabetes mellitus

A

onset of DM during pregnancy even if it persists after pregnancy

24
Q

Diagnosis of nongestational diabetes

A
  1. fasting plasma glucose (recommended test)
  2. 75 g oral glucose tolerance test
  3. hemoglobin A1c
  4. random plasma glucose in patient with classic symptoms
  • abnormal diagnostic tests should be repeated before a diagnosis is established; alternatively another test by a different method can be performed
25
Q

Diagnostic criteria for diabetes

A
26
Q

Diagnostic criteria for gestation diabetes

A
  • women with risk factors for DM should be tested at first prenatal visit (apply standard criteria for type II DM)
  • otherwise pregnant women should be screened for gestational DM at 24-28 weeks using a 75 g 2 hour OGTT after an overnight fast > 8 hours
27
Q

Monitoring diabetes patients

A
  • HbA1c used to monitor glycemic control
    • measure 2x/year in stable patients
    • goal < 7%
  • annual screening for
    • lipid disorders (adult patients)
    • microalbuminuria
    • serum creatinine to estimate eGFR
28
Q

Diabetic ketoacidosis

A
  • occurs in insulin dependent diabetics
  • hyperglycemia, ketosis, metabolic acidosis
    • glucose >=200 mg/dL
    • venous pH < 7.3 or bicarb 15 mmol/L
    • left shifted neutrophilia
    • hyperamylasemia
    • hyperlipasemia
    • increased anion gap
    • serum potassium initially elevated but severe hypoK may follow treatment
  • Major serum ketones:
    • acetone
    • acetoacetic acid
    • beta hydroxybutyrate
      • nitroprusside technique is sensitive to acetone and acetoacetic acid but not beta hydroxybutyrate, which in DKA is often 80% of serum ketones
29
Q

Hyperglycemic hyperosmolar nonketotic coma

A
  • occurs in patients with noninsulin dependent diabetes
  • altered mental status
  • profound hyperglycemia
  • hyperosmolarity
  • dehydration
  • essentially normal pH
    • glucose usually > 1000
    • osmolarity > 330
    • normal bicarb and ketones
  • High mortality

Compendium Chemistry (13 decks)

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