Lipids and Carbohydrates Flashcards
Review of lipids
- Lipoproteins contain
- Lipoprotein classes determined by, #
- Lipid metabolism
- 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


Lipid measurements
- directly measured lipids
- how is LDL determined?
- how is VLDL determined?
- lipoprotein measurement performed how?
- lipoprotein electrophoresis
- gross characteristics of lipid specimen
- 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
- invalid when
- 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
LDL calculation
- Friedewald equation
- not valid if
- TG > 400
- chylomicrons present
- cholestasis
- type III dyslipidemia

General features of lipid disorders
- consequence of hyperlipidemia (LDL versus TG)
-
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


Predominant hypercholesterolemia
- cholesterol level
- primary causes
- secondary causes
- 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:
- hypothyroidism
- diabetes mellitus
- nephrotic syndrome
- cholestasis
- cyclosporine
- thiazide diuretics
- loop diuretics
Predominant hyperTG
- secondary causes
- primary causes
- Related to elevated chylomicrons or VLDL
- Secondary causes
- heavy alcohol use
- obesity
- diabetes mellitus
- hepatitis
- pregnancy
- renal failure
- beta blockers
- isotretinoin
- corticosteroids
- nephrotic syndrome
- gout
- Primary causes
- familial combined hyperlipidemia
- familial LPL deficiency
- familial apo C II deficiency
- familial hyperTG
Mixed hyperTG and hypercholesterolemia
- most common in
- severe diabetes
- hypothyroidism
- nephrotic syndrome
- thiazides
- loop diuretics
- beta blockers
- primary causes
- familial combined hyperlipidemia
- type III hyperlipidemia (dysbetalipoproteinemia)
Low levels of HDL cholesterol
- 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
Lipids in the assessment of coronary artery disease
- major risk factors for CAD
- testing
- recommendations
- Third Adult Treatment Panel report (ATP III) lists major risk factors for CAD:
- smoking
- HTN
- low HDL
- family history of premature CAD
- 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
ATP III cholesterol classification

ATP III Recommended LDL targets according to risk group
Notes
Target LDL

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?
- 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
Glycosylated hemoglobin
- 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:

Symptoms of hypoglycemia
- 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
Hypoglycemia differential diagnosis

Drug induced hypoglycemia may be caused by
sulfonylureas (oral hypoglycemics)
alcohol
quinine
Fasting hypoglycemia
- pathophysiology
Insulinomas - presentation and pathology
- 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
- present with Whipple triad
Reactive hypoglycemia
- rapid onset hypoglycemia following a meal
- causes
- hereditary fructose intolerance
- galactosemia
- postvagotomy states (dumping syndrome)
- early type 2 DM
Type 1 DM
- 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
Type 2 diabetes
- progressive insulin resistance
- most common form of DM
- adults
- usually noninsulin dependent
Gestational diabetes mellitus
onset of DM during pregnancy even if it persists after pregnancy
Diagnosis of nongestational diabetes
- fasting plasma glucose (recommended test)
- 75 g oral glucose tolerance test
- hemoglobin A1c
- 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
Diagnostic criteria for diabetes

Diagnostic criteria for gestation diabetes
- 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

Monitoring diabetes patients
- 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
Diabetic ketoacidosis
- 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
Hyperglycemic hyperosmolar nonketotic coma
- 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