Basic Anatomy Review Flashcards
Hypothalamus releases
Corticotropin RH Gonadotropin RH Thyrotropin RH Growth hormone RH Antidiuretic hormone Oxytocin
Thyroid gland releases
Triiodothyronine (T3)
Thyroxine (T4)
Adrenal gland releases
Cortex -
aldosterone
cortisol
androgens
Medulla -
catecholamines
Testes release
testosterone
Pituitary gland releases
Anterior - Growth hormone Prolactin Luteinizing hormone Follicle-stimulating hormone Thyroid stimulating hormone Adrenocorticotropic hormone
Posterior pituitary -
Antidiuretic hormone
Oxytocin
Where are ADH and oxytocin produced
ADH and oxytocin are produced in the hypothalamus and stored in the posterior pituitary gland
Parathyroid glands release
Parathyroid hormone (PTH)
Pancreas releases
insulin
glucagon
Ovaries release
estrogen
progesterone
hypothalamic pituitary axis role
Information about cortical inputs, automatic function, environmental cues (light, temperature) and peripheral hormonal feedback is synthesized at the coordinating centre of the endocrine system, the hypothalamus.
The hypothalamus then sends signals to the pituitary to release hormones that affect the thyroid, adrenals, gonads, growth, milk production, and water balance
Adrenal gland composition and function
Each gland (6-8 g) has
1) a cortex with 3 layers that act like independent organs
(zona glomerulosa -> aldosterone,
fasciculata -> cortisol,
reticularis -> androgen and estrogen precursors), and
2) a medulla that acts like a sympathetic ganglion to store/synthesize adrenaline and noradrenaline
Function of gonads
Bifunctional: sex steroid synthesis and gamete production
Sex steroids control sexuality and affect metabolic and brain functions
Chylomicron function
Transports dietary TG from gut to adipose tissue and muscle
VLDL function
Transports hepatic synthesized TG from liver to adipose tissue and muscle
IDL function
Product of hydrolysis of TG in VLDL by lipoprotein lipase resulting in depletion of TG core
Enriched in cholesterol esters
LDL function
Formed by further removal of residual TG from IDL core by hepatic lipase resulting in greater enriched particles with cholesterol esters
Transports cholesterol from liver to peripheral tissues (gonads, adrenals)
HDL function
Transports cholesterol from peripheral tissues to liver Acts as a reservoir for apolipoproteins
Exogenous and endogenous biosynthetic lipid pathways
TN E3
Familial lipoprotein lipase deficiency etiology/pathophysiology
Autosomal recessive deficiency of lipoprotein lipase or its cofactor
Familial lipoprotein lipase deficiency labs
Increased TG
Increased chylomicrons
Moderate increase in VLDL
Familial lipoprotein lipase deficiency clinical presentation
Presents at infancy Recurrent abdominal pain Hepatosplenomegaly Splenic infarct Anemia, granulocytopenia, thrombocytopenia 2o to hypersplenism Pancreatitis Lipemia retinalis Eruptive xanthomata
Familial lipoprotein lipase deficiency treatment
Decrease dietary fat intake to <10% of total calories
Decrease dietary simple carbohydrates
Cook with medium chain fatty acids
Abstain from EtOH
Gene therapy (Glybera)
Familial hypertriglyceridemia etiology/pathophysiology
Autosomal dominant for inactivating mutations of the LP lipase gene Several genetic defects resulting in increased hepatic VLDL synthesis or decreased removal of VLDL
Familial hypertriglyceridemia labs
Increased TG
Increased VLDL
Familial hypertriglyceridemia clinical presentation
Possible premature CAD
Develop syndrome of obesity, hypertriglyceridemia, hyperinsulinemia, and hyperuricemia in early adulthood
Familial hypertriglyceridemia treatment
Decrease dietary simple carbohydrates and fat intake
Abstain from EtOH
Fibrates or niacin
Types of primary hypertriglyceridemias
Familial lipoprotein lipase deficiency
Familial hypertriglyeridemia
Secondary hypertriglyceridemia etiologies
- endocrine: obesity/metabolic syndrome, hypothyroidism (more for high LDL, not TG), acromegaly, Cushing’s syndrome, DM
- renal: chronic renal failure, polyclonal and monoclonal hypergammaglobulinemia
- hepatic: chronic liver disease, hepatitis, glycogen storage disease
- drugs: alcohol, corticosteroids, estrogen, hydrochlorothiazide, retinoic acid, β-blockers without intrinsic sympathomimetic action (ISA), anti-retroviral drugs, atypical antipsychotics, oral contraceptive pills
- other: pregnancy
Hypertriglyceridemia and pancreatitis
Serum triglyceride levels >10 mmol/L increases the risk of developing pancreatitis (even some reports of TG >5 mmol/L)
Types of primary hypercholesterolemias
Familial hypercholeseterolemia
Polygenic hypercholesterolemia
Familial combined hyperlipidemia
Familial hypercholesterolemia etiology/pathophysiology
Most commonly due to defects in the normal LDL receptor on cell membranes
1/500 in U.S. population Autosomal codominant with high penetrance More prevalent in French Canadian, Dutch Afrikanner, Christian Lebanese populations
Familial hypercholesterolemia clinical presentation
Tendinous xanthomatosis (Achilles, patellar, and extensor tendons of hand)
Arcus cornealis
Xanthelasmata
Heterozygotes: premature CAD, 50% risk of MI in men by age 30
Homozygotes: manifest CAD and other vascular disease early in childhood and can be fatal (in <20 yr olds)
Familial hypercholesterolemia treatment
Heterozygotes: improvement of LDL with statins, often in combination with ezetimibe or bile acid sequestrants or PCSK9 inhibitor
Homozygotes: partial control with portacaval shunt or LDL apheresis in conjunction with niacin; large dose statin is modestly effective; potential liver transplant; consider lomitapide (inhibitor of the microsomal TG transfer protein) and mipomersen (inhibits ApoB gene)
Familial hypercholesterolemia labs
Inc LDL
Inc TC
Familial hypercholesterolemia and cardiovascular risk calculators
- Risk calculators such as Framingham and SCORE do not apply to patients with familial hypercholesterolemia
- Consider all adults with FH as “high risk”
Polygenic Hypercholesterolemia etiology/pathophysiology
Most common
Few mild inherited defects in cholesterol metabolism
Polygenic Hypercholesterolemia labs
Inc TC
Inc LDL
Polygenic Hypercholesterolemia clinical presentation
Asymptomatic until vascular disease develops
No xanthomata
Polygenic Hypercholesterolemia treatment
Statins, ezetimibe, niacin, bile acid sequesterant, PCSK9 inhibitor
Familial Combined Hyperlipidemi etiology/pathophysiology
In many cases, over-population of VLDL and associated inc LDL 2o to excess hepatic synthesis of apolipoprotein B
Autosomal dominant
- A common disorder (1-2% of the population)
- Contributes to 1/3 to 1/2 of familial coronary artery disease
Familial Combined Hyperlipidemi labs
inc TC + G
inc VLDL
inc LDL
Familial Combined Hyperlipidemi clinical presentation
Xanthelasma
CAD and other vascular disease
Familial Combined Hyperlipidemi treatment
Weight reduction
Decrease simple carbohydrates, fat, cholesterol, and EtOH in diet
Statins Niacin, fibrates, ezetimibe, PCSK9 inhibitor
Secondary hypercholesterolemia etiologies
- endocrine: hypothyroidism
- renal: nephrotic syndrome
- immunologic: monoclonal gammopathy
- hepatic: cholestatic liver disease (e.g. primary biliary cirrhosis)
- nutritional: diet, anorexia nervosa
- drugs: cyclosporin, anabolic steroids, carbamazepine
Familial hypoalphalipoproteinemia or Familial HDL deficiency etiology/pathophysiology
Autosomal dominant inheritance of a mutation in the ABCA1 or the APOA1 gene
Familial hypoalphalipoproteinemia or Familial HDL deficiency clinical presentation
Premature atherosclerosis
Cerebrovascular disease
Premature atherosclerosis
Xanthomas
Familial hypoalphalipoproteinemia or Familial HDL deficiency treatment
Reduce the risk of atherosclerosis with lifestyle changes, management of concomitant hypercholesterol-emia, hypertriglyceridemia, and metabolic syndrome if present
Tangier disease etiology/pathophysiology
Autosomal recessive inheritance of mutations in the ABCA1 gene
Impaired HDL-mediated cholesterol efflux from macrophages and impaired intracellular lipid trafficking
Tangier disease clinical presentation
Mild hypertriglyceridemia
Neuropathy
Enlarged, orange-coloured tonsils
Premature atherosclerosis
Splenomegaly Hepatomegaly
Corneal clouding
Type 2 DM
Tangier disease treatment
Reduce the risk of atherosclerosis with lifestyle changes, management of concomitant hypercholesterol-emia, hypertriglyceridemia, and metabolic syndrome if present
Low HDL secondary causes
- endocrine: obesity/metabolic syndrome, DM
- drugs β-blockers, benzodiazepines, anabolic steroids
- other acute infections, inflammatory conditions
Treatment effect of LDL reduction
Each 1.0 mmol/L decrease in LDL corresponds to 20-25% relative risk reduction in cardiovascular disease
Dyslipidemia and the risk for coronary artery disease
- increased LDL is a major risk factor for atherosclerosis and CAD as LDL is the major atherogenic lipid particle
- increased HDL is associated with decreased cardiovascular disease and mortality
- moderate hypertriglyceridemia (triglyceride level 2.3-9 mmol/L) is an independent risk factor for CAD, especially in people with DM and in post-menopausal women
- treatment of hypertriglyceridemia has not been shown to reduce CAD risk
What is the 6% rule
if dose of statin is doubled there is ~6% inccrease in the LDL lowering efficacy
When to screen for dyslipidemia
• screen men >40 yr, women >50 yr or post-menopausal
• if following risk factors present, screen at any age:
■ DM
■ current cigarette smoking or COPD
■ HTN (sBP >140, dBP >90)
■ obesity (BMI >27 kg/m2)
■ family history of premature CAD
■ clinical signs of hyperlipidemia (xanthelasma, xanthoma, arcus cornealis)
■ evidence of atherosclerosis
■ inflammatory disease (rheumatoid arthritis, SLE, psoriatic arthritis, ankylosing spondylitis, inflammatory bowel disease)
■ HIV infection on highly active anti-retroviral therapy (HAART)
■ chronic kidney disease (estimated GFR <60 mL/min/1.73 m2)
■ erectile dysfunction
screen children with a family history of hypercholesteerolemia or chylomicronemia
for statin follow-up
- Liver enzymes and lipid profile: liver enzymes measured at the beginning of treatment then once after therapy initiated. Lipids (once stabilized) measured annually. Order both if patient complains of jaundice, RUQ pain, dark urine
- CK at baseline and if patient complains of myalgia
- D/C statin if CK >10x upper limit of normal or patient has persistent myalgia
Factors affecting dyslipidemia risk assessment
• metabolic syndrome
• apolipoprotein B (apo B)
■ each atherogenic particle (VLDL, IDL, LDL, and lipoprotein A) contains one molecule of apo B
■ serum [apo B] reflects the total number of particles and may be useful in assessing cardiovascular risk and adequacy of treatment in high risk patients and those with metabolic syndrome
• C-reactive protein (hs-CRP) levels
■ highly sensitive acute phase reactant
■ may be clinically useful in identifying those at a higher risk of cardiovascular disease than predicted by the global risk assessment
Dyslipidemia practice guidelines
ACC/ AHA is no longer recommending a Treat to Target” approach for statin theapy Primary prevention in patients with increased risk should be treated with moderate to high intensity statin therapy without tracking LDL targets. Similarly, patients needing secondary prevention should receive high intensity statn therapy without attention to LDL targets
Primary prevention for dyslipidemia
■ estimate 10 yr risk of CAD using Framingham Risk Score (FRS) model
■ establish treatment targets
■ low FRS does not require statin treatment
Statin indicated conditions
Clinical atherosclerosis
Abdominal aortic aneurysm
DM >15 yr duration and age older than 30 yr
DM with age older than 40 yr
DM with microvascular disease
Chronic kidney disease and age older than 50yr
LDL-C≥ 5mmol/
Statin indicated conditions primary target LDL-C
≤2 mmol/L
or ≥50% decrease in LDL
For LDL-C ≥5mmol/L: 50% decrease in LD
Statin indicated conditions alternate target
apo B ≤0.80 g/L
or non-HDL-C
≤2.6 mmol/L
What is considered high and intermediate risk FRS
High risk FRS 20%+
Intermediate risk FRS 10-19%
When to initiate treatment of dyslipidemia with statins outside of statin indicated conditions
high or intermediate risk FRS
LDL >3.5 mmol/L
For LDL-C<3.5 consider if: apo B ≥1.2 g/L or non-HDL-C ≥4.3 mmol/L
dyslipidemia outside of statin indicated conditions primary target LDL-C
≤2 mmol/L
or ≥50% decrease in LDL
dyslipidemia outside of statin indicated conditions alternate target
apo B ≤0.80 g/L
or non-HDL-C ≤2.6 mmol/
Treatment of hypercholesterolemia
Conservatve:
4-6 mo trial unless high risk group, in which case medical treatment should start immediately
Diet: Decrease fat: <30% calories Decrease saturated fat: <10% calories Decrease cholesterol: <200 mg/d Increase fibre: >30 g/d Decrease alcohol intake to ≤1-2 drinks/d Smoking cessation Aerobic exercise: ≥150 min/wk in bouts of ≥10 min Weight loss: target BMI <25
Medical: HMG-CoA reductase inhibitors, ezetimibe, bile acid sequestrants, niacin
Treatment of hypertriglyceridemia
Conservative: 4-6 mo trial Diet: Decrease fat and simple carbohydrates Increase omega-3 polyunsaturated fatty acid Control blood sugars Decrease alcohol intake to ≤1-2 drinks/d Smoking cessation Aerobic exercise: ≥150 min/wk in bouts of ≥10 min Weight loss: target BMI <25
Medical: fibrates, niacin
Indications for medical: Failed conservative measures
TG >10 mmol/L (885 mg/dL) to prevent pancreatitis
Combined hyperlipidemia
Rosuvastatin to prevent vascular events in men and women with elevated CRP
Statins reduce the incidence of major cardiovascular events even in healthy people without hyperlipidemia but with elevated creactive protein.
