ENDOCRINOLOGY AND METABOLIC DISEASES
MODUL II C
HYPERLIPOPROTEINEMIAS AND PATHOGENESIS OF ATHEROSCLEROSIS
1. Physiology of lipoproteins
a. Lipoprotein classes
b. Lipoprotein composition
c. Lipoprotein synthesis and function
d. Reverse cholesterol transport
e. Physiological values of basic lipid parameters
2. Hyperlipidemia
a. Types of hyperlipidemia
b. Pathophysiology mechanisms of HL
c. Secondary HL
3. Therapy of HL
a. Dietary therapy
b. Hypolipidemic drugs (types of, indications, side effects)
c. Therapy goals in primary and secondary HL
4. Atherosclerosis
a. Pathogenesis of atherosclerosis (endotelial dysfunction, stable and unstable placque, composition of atheroma)
b. Risk factors of atherosclerosis
c. Clinical manifestation of atherosclerosis
d. Theoretical possibilities of treatment of atherosclerotic diseases
OBESITY
A. Demonstration of a patient
I. History of an obese patient
a. Ethiopathogenetics factors of obesity endogenic (genetics, endocrine factors etc.) and exogenic factors (nutrition,
physical activity, social environment, psychosocial aspects)
b. Complications of obesity (metabolic complications, cardiovascular, endocrine, gastrointestinal, urogenital and
musculosceletal diseases)
II. Examination of an obese patient with respect to the above mentioned factors
III. Basic approach to the therapy of obesity
B. Seminar
I. Definition of obesity
II. Evaluation methods of body composition and fat distribution
III. Clinical aspects of obesity
IV. Ethiopathogenesis of obesity – new findings (candidate genes regulating the energy metabolism, dietary intake,
metabolism of fat tissue)
V. Treatment of obesity today
Literature: Kopelman PG : Clinical Obesity , Blackwell Science, Oxford 1998; Internet: www.obesita.cz; www.nugenob.com
NUTRITION STATUS OF A PATIENT, METHODS OF EVALUATION
1.
2.
3.
4.
Personal and family history, nutrition history
Clinical investigation (aspection and basic physical methods for malnutrition evaluation)
Biochemical examination of blood and urine
Anthropometric measurements, body height and weight, wait to hip ratio, BMI calculation, measurement of subcutaneous
fat layer
5. Evaluation of nutritional consumption
Nutrition toxicology
1. Toxic substances in the food, their evaluation and risk regulation. Biotransformation and interaction of toxic substances in
the body, possibilities of therapy. Impact on the organism. Limits. Monitoring.
2. PCB, DBF and dioxines
3. Possibilities of exposition. TDI.
4. Toxic congeners PCB, PCBF, PCDD. International toxic equivalent (I-TEQ).
5. Risk for health. PCB as endocrine disruptor.
6. Phtalic acid esters (sources of exposition, limits, toxic effects, risk for health)
7. Dietary toxic substances for thyroid gland
8. Mycotoxines
Vitamins – homework
Fat soluble and water soluble vitamins – sources, needs, function, symptoms of hypo- and hypervitaminosis of each vitamin
CLINICAL NUTRITION
1. Risks and consequences of malnutrition
- general risks of malnutrition
- consequences of malnutrition for critical patient, clinical foundations with specific nutritional deficiency, medication
with impact on nutrition
2. Diagnostics of malnutrition
- clinical methods of nutrition status of evaluation
- physical examination and history
- body height, weight, BMI, anthropometric data
- nutritional score systems: SGA, MNA, PNI
- laboratory methods
- indirect calorimetry
- bioimpedance
- energy and metabolic balance
3. Nutritional support, parenteral and enteral nutrition
- options for nutritional support
- specific aspects of parenteral (PN) and enteral (EN) nutrition
- physiology effects, advantages and disadvantages of EN
- how to perform EN
- difficulties, risk and complications of EN
- physiology effects, advantages and disadvantages of PN, all-in-one system
- how to perform PN
- difficulties, risk and complications of PN
- methodology of nutritional support, perioperative PN and EN
4. Nutritional support in special situations
- critically ill patient
- perioperative nutrition
- gastroenterology
- short bowel syndrome
- oncology
- gerontology
- out-patient forms of nutrition support
BODY FLUIDS AND ITS MOST IMPORTANT IONS
A. Repetition – Na+, K+
1. Normal values
2. Importants
3. Hormone regulations (aldosteron, ADH, ANF)
4. Pathophysiology: causes and mechanisms of sodium and potassium dysbalance
B. Calcium
1. Normal values (total stores in the body)
2. Impacts
a. neuromuscular excitability
b. excitation – contraction in smooth muscle and myocardial cells
c. messenger (in target cells of endocrine system)
d. tight junction between cells
e. coagulations
3. Metabolism of calcium – short time and long time regulation
4. Hormonal regulation
a. PARATHORMON:
parathyroid
effect on bone (rapid and slow release of calcium from bones)
effect on kidneys (calcium reabsorption, phosphate excretion, vit.D activation
b. CALCITONIN
c. VITAMIN D
5. Calcium metabolism disturbances (their causes and consequences)
a. hyperparathyroidism: primary-, secondary-, tertiaryb. hypoparathyroidism
c. vitamin D: hyper- and hypovitaminosis
hypocalcemia
hypercalcemia
bone metabolic disease
Literature:
Calcium metabolism:
http://blue.vm.temple.edu/~pathphys/general/tablecontents.html
http://www.merck.com/pubs/mmanual/section2/chapter12/12d.htm
The Thyroid and Parathyroid Glands:
http://arbl.cvmbs.colostate.edu/hbooks/pathphys/endocrine/thyroid/index.html
http://endocrinesearch.com/
Control of Ca and Phosphate:
http://www.members.aol.com/Bio50/LecNotes/lecnot34.html
Metabolic Bone Diseases
http://edcenter.med.cornell.edu/CUMC_PathNotes/Skeletal/Bone_04.html
BASIC PATOPHYSIOLOGY OF ENDOCRINE SYSTEM
I. Endocrine glands
II. Definition of hormones
A. Traditional: Informative molecule produced and liberated by specific endocrine gland in to the blood stream and
to distant target organs. There the hormone introduces physiologic respond (the hormone changes the speed
and extension of the existing reaction or initiates a new reaction.
B. Modified definition – depends on different compartments of action
1. endocrine
2. paracrine
3. autocrine
4. neuroendocrine
5. immune
C. Comparison with nervous and immune system
III. Role of endocrine glands
A. Synthesis of hormones
B. Storages of hormones
C. Secretion of hormones
IV. Transport of hormones – the levels of circulatory hormones depend on:
A. The rate of secretion
Stimulators of secretion
1. Chemical stimules e.g. glucose stimulates secretion of insulin in pancreas
2. Neural stimules e.g. acetylcholine stimulates secretion of epinephrin and norepinephrin in adrenal
medulla
3. Hormonal stimules e.g. ACTH stimulates secretion of glucocorticoids in adrenal coretex
B. The rate of metabolism
Halftime in blood
Peptides to 2-30 min. OXY, MSH
Proteins 60 min. TSH
Steroides 20 – 120 min. cortisol
C. Hormone-binding-proteins – esp. steroids and catecholamines
Hormone (active)+ blood proteins ↔ hormone-binding-protein (inactive)
1. Increased solubility
2. Increased halftime in blood
D. Role of transport and degradation in pathology
E. Recognition of hormones by target cells through specific receptors
1. Structure of receptors – proteins
2. Binding of hormones with high affinity
3. Concentration of hormone in target cells
4. Binding of a hormone causes a chain of reactions leading to a biology response
5. The interval between hormone binding and biology response is variable
Type of hormone
Binding-response interval
neurotransmiters
miliseconds
peptides
seconds-minutes
proteins
minutes-hours
steroids
hours-days
6.
Number of receptors varies
7.
Receptors are localised
a. in the cell membrane on the surface
b. in the nucleus of the target cells
V. Methods of measurement
A. Hormonal levels
1. bioassay
2. chemical analysis
3. radioimmunoassay
B. Specific receptors
C. Clearance
VI. Endocrinopathy
A. Hyposecretion – treated with hormone substitution
B. Hypersecretion – treated:
1. surgical removal of the gland and hormone substitution
2. Radioactive destruction of the gland and hormone substitution
3. Hormonal antagonists
C. Insensitivity or resistance of target organ – the most difficult treatment
D. Ectopic tumors – no negative feedback mechanism
HYPERTHYROIDISM AND HYPOTHYROIDISM
1. Brief recapitulation of synthesis and metabolism of thyroid hormones and their regulation
2. Brief recapitulation of thyroid hormones function
3. Syndromology of thyroid gland diseases and basics of diagnostics
a. local syndrome
b. dysfunction
c. immunopathology
PHARMACOLOGY
Insulin
-
physiology, basal and stimulated secretion
indications of insulin therapy
tactics of insulin therapy (conventional, intensified)
classification of insulin
Peroral antidiabetic drugs
- sulfonylureas – mechanism of action, main representatives, side effects
- biguanides – mechanism of action, main representatives, side effects
- inhibitors of intestinal glycosidase – mechanism of action, main representatives, side effects
- thiazolidinediones (glitazones) – mechanism of action, main representatives, side effects
- rapid insuline secretion stimulators – mechanism of action, main representatives, side effects
Hormonal replacement therapy
- effect on climacteric syndrome and long term risks
- osteoprotective and cardioprotective effects of HRT
- therapeutic regimens, active substances
- indication, contraindication, side effects
- selective estrogene receptors modulators (SERM)
Antihormones
- antiestrogenes – tamoxifen – mechanism of action, indication
- mifepriston, aromatase inhibitors
- antiandrogenes – types of, mechanism of action, indication
Pharmacotherapy of osteoporosis
- antiresorption drugs, HRT, bisphosphonates, calcitonin, SERM
- mechanism of action, principles and risk of therapy
Corticosteroids
- types of, mechanism of action
- substitution therapy
- intensive short therapy, pulse therapy
- long term and chronic therapy
- indications and therapy strategy
- side effect and contraindications
Drugs used for treatment of obesity
- drugs decreasing energy intake vs. drugs increasing energy expenditure
- sibutramin, orlistat
- mechanism of action
- principles and risk of therapy