Normal Growth & Clinical Aspects Flashcards
What Factors Regulate Growth?
- GROWTH HORMONE (regulated by balance of GHRH vs. GHIH from hypothalamus)
- THYROID HORMONES
- INSULIN (imp. in causing growth - T1DM will have slightly smaller statures)
- SEX STEROIDS (pubertal growth spurt)
- AVAILABILITY OF NUTRIENTS
- STRESS (inhibits growth)
- GENETICS
What is Growth Hormone + What 2 neurohormones control its release?
Peptide hormone released by the anterior pituitary
Transported bound to carrier proteins
Growth Hormone Releasing Hormone & Growth Hormone Inhibiting Hormone
Primary Actions of Growth Hormone + are they Direct/Indirect?
- GROWTH & DEVELOPMENT (INDIRECT ACTION)
2. REGUATION OF METABOLISM (DIRECT ACTION)
How does GH itself impact growth & development + does it req. any other hormones?
GH NECESSARY FOR GROWTH & DEVELOPMENT > 8 MONTHS
REQUIRES PERMISSIVE ACTION of THYROID HORMONES & INSULIN TO STIMULATE GROWTH
GH SECRETION CONTINUES THROUGHOUT ADULT LIFE = ESSENTIAL FOR TISSUE REPAIR & MAINTENANCE
HOW DOES GH STIMULATE GROWTH IN ITS TARGET TISSUES:
* STIMULATES CELL SIZE = HYPERPLASIA * STIMULATES CELL DIVISION = HYPERPLASIA
What is Insulin-like growth factor 1 + what significance does GH have on it’s secretion?
- SIMILAR STRUCTURE TO PROINSULIN (it’s a PEPTIDE HORMONE) - TRANSPORTED BOUND TO CARRIER PROTEINS
- BINDS TO RECEPTORS SIMILAR TO INSULIN RECEPTOR = HYPOGLYCAEMIA QUALITIES (limited to glucose uptake in muscle as liver & adipose tissue has few IGF receptors)○ GH HAS HYPERGLYCAEMIC EFFECTS (& tends to be stronger than IGF-1)
GH actions on growth mainly indirect via activation of IGF-1 secretion
IGF-1 Feedback Loop on GH Release
- IGF-1 = -VE FEEDBACK ON GH RELEASE: INHIBITS GHRH & ACTIVATES GHIH
- ALSO, -VE FEEDBACK LOOP OF GH INHIBITING GH RELEASE FROM SOMATOTROPHS IN PITUITARY
GH/IGF-1 Effects on Bone Growth
- GH STIMULATES CHONDROCYTE PRECURSOR CELLS/PRECHONDROCYTES IN EPIPHYSEAL PLATES TO DIFFERENTIATE INTO CHONDROCYTES
- DURING DIFFERENTIATION, CELLS BEGIN TO SECRETE IGF-1 & BECOME RESPONSIVE TO IGF-1
- IGF-1 THEN ACTS AS AUTOCRINE/PARACRINE AGENT TO STIMULATE DIFFERENTIATING CHONDROCYTES TO UNDERGO CELL DIVIION + PRODUCE CARTILAGE
EPIPHYSEAL PLATES CLOSE DURING ADOLESCENCE UNDER INFLUENCE SEX STEROIDS (induces apoptosis of chondrocytes) - THEN LONGITUDINAL GROWTH NO LONGER POSS.
How does GH regulate metabolism + why are both insulin & GH req. for growth?
- INCREASES GLUCEONEOGENESIS BY LIVER
- REDUCES ABILITY OF INSULIN TO STIMULATE GLUCOSE UPTAKE BY MUSCLE & ADIPOSE TISSUE
- MAKES ADIPTOCYTES MORE SENSITIVE TO LIPLYTIC STIMULI
- INCREASES AA UPTAKE & PROTEIN SYNTHESIS in almost all cells
NEED BOTH INSULIN & GH FOR GROWTH
• GH STOPS MUSCLE & ADIPOSE TISSUE FROM USING GLUCOSE (muscle can use free FA readily) - GREATLY INCREASES BONE & BRAIN DEVELOPMENT + MUSCLE DEVELOPMENT VIA AA UPTAKE
How is GH secreted (is it constant? + how does this impact clinical monitoring) + during the day when is it released?
- LARGE QUANTITIES OF GH PRESENT IN PITUITARIES OF BOTH ADULTS & CHILDREN - highest rates of secretion occuring in teenagers
- SECRETION RATE UNDERGOES RAPID SPONTANEOUS FLUCTUATION + INCREASE/DECREASE IN RESPONSE TO SPECIFIC STIMULI○ MOST RELEASED DURING 1ST 2HRS OF SLEEP (deep delta sleep) + as ENERGY REQ. LOW, ENERGY DIVERTED TO GROWTH○ GH LVLS DURING WAKING HRS ARE LOW○ NEED TO HAVE REPEATED MEASUREMENTS OVER 24 HRS TO GET ACTUAL PICTURE OF GH RELEASE○ HOWEVER, PLASMA LVLS OF IGF-1 RELATIVELY CONSTANT - IGF-1 may buffer varied lvls of GH lvls
Control of GH Secretion
HEAVILY INFLUENCED BY NUTRITIONAL STATUS (which is mainly mediated by hypothalamic control of GHIH vs. GHRH)
STIMULI INCREASING GHRH SECRETION & GH:
1. ACTUAL/POTENTIAL DECREASE IN ENERGY SUPPLY TO CELLS (maintains tissue + their energy supply) 2. INCREASED AMOUNTS OF AMINO ACIDS IN PLASMA 3. STRESSFUL STIMULI 4. DELTA SLEEP 5. OESTOGEN & TESTORONE (+ decreases IGF mediated -ve feedback)
STIMULI INCREASING GHIH & REDUCING GH:
1. GLUCOSE 2. FFA 3. REM SLEEP 4. CORTISOL
Physiology of Growth (3 main factors)
- Hormones: GH, IGF-1, thyroid hormones, sex steroids, glucocorticoids, insulin
diff. hormones responsible for diff. periods of growth - Nutrition: adequate nutrition req. for in utero & development
injury & disease stunt growth by causing protein catabolism via glucocorticoid effects
- Genetics: can help determine max. growth
Why are thyroid hormones important in growth + do they affect any other hormones?
- ESSENTIAL FOR NORMAL GROWTH esp. NERVOUS SYTEM DEVELOPMENT IN UTERO + EARLY CHILDHOOD
- THYROID HORMONES = WIDESPREAD EFFECTS ON OSSIFICATION of CARTILAGE & TEETH MATURATION + CONTOURS OF FACE & PROPORTIONS OF BODY
- EFFECTS = PERMISSIVE TO GH/IGF-1
Cretinism
Hypersecretion of GH & 2 poss. conditions that may arise
ENDOCRINE TUMOURS USUALLY THE CAUSE
MANAGEMENT: SURGICAL REMOVAL of TUMOUR/SOMATOSTATIN ANALOGUES
GIGANTISM:
EXCESS GH from PITUITARY TUMOUR BEFORE EPIPHYSEAL PLATES of LONG BONES CLOSE
Causes EXCESSIVE GROWTH
ACROMEGALY:
EXCESS GH from PITUITARY TUMOUR AFTER EPIPHYSEAL PLATED HAVE SEALED
LONG BONES CANNOT GROW = NO LONGTUDINAL GROWTH = NO HEIGHT INCREASE
CAN GROW IN OTHER DIRECTIONS:
* ENLARGING HANDS & FEET & JAW * ORGANS MAY ENLARGE * OSTEOARTHRITIC VERTEBRAL CHANGES * HIRSUTISM * GYNECOMASTIA & LACTATION
Causes of Reduced Growth (in reference to GH) + explain
- GHRH DEFICIENCY = HYPOTHALAMIC ORIGIN
- GH SECRETING CELLS ABNORMAL = PITUITARY ORIGIN
- END ORGAN UNRESPONSIVE TO GH (LARON DWARFISM)
- GENETIC MUTATIONS
- PRECOCIOUS PUBERTY
- HYPOTHYROID CHILDREN
Cretinism
HYPOTHYROID CHILDREN FROM BIRTH
§ FAILURE OF NORMAL GROWTH DUE TO LOSS OF TH' PERMISSIVE ACTIONS ON GH § Soooo…. RETAIN INFANTILE FACIAL FEATURES = HYPOTHYROID DWARF § GH LVLS NORMAL
