Basal Humanbiologi Endokrinologi
| Basal Humanbiologi |
Kemiske hovedtyper af humorale mediatorer
redegøre for principper for deres virkning på organismens celler, illustreret med eksempler fra konkrete organsystemer
- Membrane impermeable (amines, peptides, proteins, glycoprotein)
- First messenger: its receptor has binding site and activity site. Hormone bind to binding site of receptor, alter activity site, thus alter function of enzymes or membrane transport mechanisms.
- Second messenger are molecules that relay signals received at receptors on the cell surface to target molecules in the cytosol and/or nucleus; also greatly amplify the strength of signal.
- cAMP second-messenger system (adrenalin, glucagon, LH): protein hormone-receptor coupling > Gs (transducer protein) + GTP > adenyl cyclase activation > ATP > cAMP > protein kinase (A) activation > phosphorylation of membrane and nuclear proteins > secretory events, genomic expression.
inositol-1,4,5-trisphosphate (IP3) (peptide, protein) 1. hydrolyzes phospholipids in the inner layer of the plasma membrane. Hydrolysis of PIP2 yields IP3. 2. This soluble molecule diffuses through the cytosol and 3. binds to receptors on the endoplasmic reticulum causing 4. the release of calcium ions (Ca2+) into the cytosol. 5. The rise in intracellular calcium triggers the response.
Example A: the calcium rise is needed for NF-AT (the "nuclear factor of activated T cells") to turn on the appropriate genes in the nucleus.
Example B: Parathyroid gland (2nd messager) secrete parathyroid hormone (PTH), amino acids, ↑ concentration of Ca2+ in blood in three ways.
PTH promotes:
- release of Ca2+ from the huge reservoir in the bones.
- reabsorption of Ca2+ from the fluid (urine) in the tubules in the kidneys → Vitamin D3.
- absorption of Ca2+ from the contents of the intestine (mediated by vitamin D)
PTH also regulates level of P in the blood. Secretion of PTH reduces efficiency of which phosphate is reclaimed in the proximal tubules of the kidney, causing drop in P concentration of the blood.
Cells of parathyroid glands have surface G-protein-coupled receptors bind Ca2+ (the same type of receptor is found on the calcitonin-secreting cells of the thyroid and on the calcium absorbing cells of the kidneys). Binding of Ca2+ to receptor depresses the secretion of PTH, leads to lowering of concentration of Ca2+ in the blood.
- Membrane permeable (steroids)
Steroids: hydrophobic, carried in blood by transport proteins. 1. Diffuse through lipid into the cells. 2. bind with intracellular protein receptor within nuclear matrix, to regions of the target cell's DNA and activates specific genes. 3. activates messenger RNA (mRNA) synthesis 4. mRNA leaves nucleus 5. guides protein synthesis, which may be enzymes, transport proteins, hormone receptors. Exert characteristic effect.
- Prostaglandins
Lipids, synthesized by arachidonic acid in cell membrane. Local, often affecting only the organ where they are produced. They are rapidly inactivated.
Glands
Redegøre for anatomiske og funktionelle hovedtræk (derunder regulationen af ormonsekretionen og hormonernes virkninger), ved hypothalamus-hypofyse, binyrebark g -marv, gl. thyreoidea og parathyreoideae, den endocrine pancreas, samt for nyrens endocrine betydning. (following glands regulated by anatomy, effect, regulation, disorder)
Regulation of hormone secretion: (3 kinds) 1. Negative feeback: Gland A secretes hormone, stimulates gland B to ↑ secretion of another hormone. hormone from gland B alters target cells, inhibits activity of gland A. (hypothalamus – pituitary gland) 2. Nervous system directly controls secretion 3. glands directly responds to changes in the composition of internal environment.
- Pituitary gland (hypophysis)
Anterior pituitary (adenohypophysis), connects to hypothalamus via phypophseal portal veins, mainly glandular epithelial cells. Posterior pituitary (neurohypophysis), enlarged distal end of the infundibulum, connects to hypothalamus via neuroendocrine cells, mainly nerve fibers originate from hypothalamus, neuroglial cells.
Anterior pituitary hormones: (protein/peptide)
Somatotropin(GH): target: liver. Effect: somatomedin secretion, tissue growth, enchances movement of amino acids across cell membrane.
Prolactin(PRL): target: mammary glands, testes. Effect: milk synthesis.
Thyroid stimulating hormone (TSH) : DUH!
Adrenocorticotropic hormone (ACTH): target: adrenal cortex. Effect: secretion of glucocorticoids
Follicle-stimulating hormone (FSH) + Luteinizing hormone (LH): gonadotropins = reproduction glands.
Posterior pituritary hormones:
Antidiuretic hormone (ADH): target: kidney. Effect: water retention via urine, (osmotic pressure)
Oxytocin (OT): target: uterus, mammary gland. Effect: labor contractions, milk release, ejaculation, stimulates smooth muscles in the uterine wall.
- Disorder example: too little ADH → diabetes insipidus, excess urine production.
- Thyroid gland (controlled by thyroid stimulating hormone from anterior hypophysis)
Anatomy: composed of two lobes connected by a narrow band of thyroid tissue, isthmus. Lobes are lateral to upper portion of the trachea, inferior to the larynx, isthmus extends across the anterior aspect of the trachea. It is highly vascular and appears more red in color. Parathyroid is redder in histology, but not in reality.
Tetraiodothyronine, T4, Triiodonthyronine, T3: target: most tissues. Effect: determines basal metabolic rate (BMR), ↑ rate of protein synthesis, lipid breakdown. Fetal, child growth, CNS development. T3 is more effective than T4, otherwise no difference.
Calcitonin:from parafollicle cells, thyroid gland. Target: bone. Effect: inhibit osteoclasts, stimulate osteoblast, decrease calcium blood level. Though mostly PTH controls the level.
Regulation: 1. Hypothalamus releases thyroid hormone (TRH) through hypothalamophyseal portal blood vessels to anterior hypophysis. 2. secrete TSH. 3. via general circulation to thyroid gland, secrete T3, T4. 4. T3, T4 inhibits secretion of TRH, TSH. (negative feedback)
Disorder:Hypothyroidism → cretinism, stunted growth, abnormal bone formation, low body temperature, retarded mental development. Hyperthyroidism → restlessness, overeating, exophthalmos (eyes protrude)
- Parathyroid gland
Anatomy:embedded in posterior of each lobe of the thyroid gland, usually four parathyroid glands. Their cells are organized in densely packed masses or cords rather than in follicles.
Function: secretion of parathyroid hormone (PTH), see example in 6.1
Regulation: calcium blood level. (regulation type 3)
Disorder:hyperparathyroidism, bone soften, deform, easily fracture, excess CaP may cause kidney stone. Hypoparathyroidism, blood calcium level decreases, nervous system become abnormally excitable, muscles undergo tentanic contraction → respiratory failure → death.
- Adrenal gland
Anatomy: near the superior pole of each kidney, surrounded by abundant adipose tissue, composed of inner medulla and cortex. Medulla cells are modified postganglionic neurons. Cortex: epithelial cells.
Function:Adrenal medulla: prepare autonomic nerve system for energy expending action. Epinephrine, norepinephrine
Adrenal cortex: VITAL.
Aldosterone: (mineralocorticoid) conserve Na+ ion reabsorbed i kidney tubules, excrete K+ ions. Independent of hypophysis. Factor: electrolyte concentrations in body fluids.
Regulation: Negative feeback. In case of blodtab → ekstracellular volume ↓ → Na+ ↓ → nyre sensor → rennin udskilles til blodet → angiotensin II hormone → adrenal cortex aktiveres → ↑ aldosterone → Na+ reabsorbtion i nyren.
Cortisol: VITAL (glucocorticoid) dependant of hypophysis/thalamus. Inhibits protein synthesis, stimulate liver to synthesis glucose; use fatty acids as energy source than glocuse → blood glucose concentration ↑
Regulation: CRH, ACTH promotes, cortisol inhibits CRH, ACTH secretion. (negative feedback)
Sex hormone: duh!
Disorder:Tumors in medulla → release of norepinephrine dominates → high blood pressure, increased heart rate, blood sugar.
Cortex:Hyposecretion → Addison → ↓ Na+ → ↑ K+ → hypoglycaemia, dehydration, low blood pressure, ↑ skin pigment. Hypersecretion (tumor): oversecreting ACTH → crushing syndrome → overproduce mineralocorticoids, glucocorticoids → blood glucose high, deplete tissue protein, excess sex hormone.
- Pancreas
Anatomy: two major types of secretory tissues. exocrine gland; an endocrine gland releases hormones. endocrine function is localized in the islet cells (islets of Langerhans), synthesize and secrete hormones including insulin (β cell) and glucagons (ά cell).
Function:
Insulin (β cell): target: promotes movement of glucose into cells, stimulate liver to form glycogen from glucose + inhibits conversion of noncarbohydrates into glucose.
Glucagons (ά cell): opposite effect of insulin, same target.
Regulation: negative feedback system sensitive to blood glucose conc., receptors ά, β cells.
Diabetes:
Type1: immune system destroy beta cells. Inhibit protein, fat synthesis, tissue waste away, lose weight, very hungry, fatigues easily, decreasing ability to grow and repair tissue. Fatty acoid, ketone accumulate in blood, acidosis. Dehydration, acidosis → disorientation, coma, death.
Type 2: beta cells function, body cells lose sensitivity. Coronary artery disease, retinal, nerve damage.
Stress
Redegøre for organismens respons på stress som et vigtigt eksempel på den integrerede neuro-hormonale styring af organismens funktioner.
Stress:
Increase ACTH secretion by stimulating the release of CRH.
Hypothalamus releases sympathetic impulses to adrenal medulla in response to stress, secrete epinephrine, norepinephrine. ↑ of glocuse from liver, ↑ heart rate, ↓ function of visceral organs, ↓ blood pressure, ↑ release of fatty acid from fat stores.
Hypothalamus releases more CRH → higher cortisol → frigørlese af energi fra sukker og fedtdepoter (modsat insulin, med glukagon, adrenalin), nydannelse af glucose, hjerte/kar kontraktion.