Lecture 8 Flashcards
OSTEOCLAST FORMATION REGULATION AND ACTIVITY (3 STEPS)
- ) PROLIFERATION/DIFFERENTIATION - MONONUCLEAR PRECURSOR CELLS W/ HEMATOPOIETIC LINEAGE FUSE => MULTINUCLEATED OSTEOCLASTS
- ) ACTIVATION OF OSTEOCLAST PRECURSOR WHEN RANKL BINDS TO RANK ON OSTEOCLAST SURFACE (OPG CAN INTERFERE W/ THIS REACTION AND STOP OSTEOCLAST ACTIVATION BY BINDING TO RANKL)
- ) RUFFLED MEMBRANE SECRETES H+ ENZYMES => ACIDIC ENVIRONMENT (PROMOTES DEGRADATION OF ORGANIC/INORGANIC PORTION OF BONE INTO COMPARTMENT
RUFFLED MEMBRANE
- CA CATALYZES FORMATION OF H2O AND CO2 W/IN RUFFLED MEMBRANE AND COMBINES THEM TO FORM BICARBONATE (PROVIDES H+ IONS FOR ACIDIC ENVIRONMENT)
- DEGRADATION PRODUCTS FROM BREAKDOWN OF BONE INTO CA2+ AND PO4(3-) AND COLLAGEN FRAGMENTS ARE REABSORBED BY RUFFLED MEMBRANE AND EXCRETED VIA VESICULAR EXCRETION
ENZYMES INVOLVED IN OSTEOCLASTIC BONE BREAKDOWN
1.) LYSOSOMAL ENZYMES
2.) MATRIX METALLOPROTEINASES
RELATIONSHIP BETWEEN ENZYMATIC AND CHEMICAL ACTIVITY IS IMPORTANT
TUMOR CELL EFFECTS ON OSTEOCLASTIC ACTIVITY
TUMOR CELLS PRODUCE FACTORS (PTHrP - PARATHYROID HORMONE-RELATED PROTEIN) THAT PROMOTE FORMATION/ACTIVATION OF OSTEOCLASTS => BONE RESORPTION AND RELEASE OF FACTORS BY BONE MATRIX (TGF-β) WHICH STIMULATES TUMOR CELL PROLIFERATION
PTHrP
BLOCKS OPG AND ACTIVATES RANKL
BONE GROWTH
BONE GROWS IN LENGTH @ THESE VARIOUS SITES -
1) CARTILAGE GROWS ON THE ENDS OF THE ARTICULAR CARTILAGE
2) CARTILAGE REPLACED BY BONE ON THE INSIDE OF THE ARTICULAR CARTILAGE
3) CARTILAGE GROWS AT THE EPIPHYSEAL PLATE OUTER EDGE
4) CARTILAGE REPLACED BY BONE AT THE EPIPHYSEAL PLATE INNER EDGE
THIS OCCURS UNTIL EPIPHYSEAL PLATES (COMPOSED OF HYALIN CARTILAGE) CLOSE
BONE REMODELING IN SPONGY/CORTICAL BONE
DIAPHYSIS IS REMODELED -
SPONGY BONE IS REMODELED EVERY 3-4 YEARS
CORTICAL BONE IS REMODELED EVERY 10 YEARS
PROCESS IS CONTINUAL - NEVER AT METABOLIC REST
PRODUCES LYSOSOMAL ENZYMES AND ACIDS
BONE REMODELING
- ) BONE RESORBED AT BONE HEAD/NECK JUNCTURE
- ) BONE ADDED BY APPOSITIONAL GROWTH AT THE SURFACE OF THE EXTERIOR DIAPHYSIS
- ) BONE RESORBED ON THE INTERIOR SURFACE OF THE DIAPHYSIS
REMODELING UNITS
MADE UP OF A COMPOSITE OF OSTEOBLASTS AND OSTEOCLASTS
EPIPHYSEAL PLATE CARTILAGE ORGANIZATION
Real People Have Career Options
- ) RESTING ZONE - SMALL INACTIVE CARTILAGE CELLS
- ) PROLIFERATION ZONE - QUICKLY DIVIDING (REPEATED MITOSIS) CHONDROBLASTS (PUSH EPIPHYSIS AWAY FROM DIAPHYSIS => LENGTHENING)
- ) HYPERTROPHIC ZONE - OLDER CHONDROCYTES ENLARGE AND SIGNAL TO THE SURROUNDING MATRIX TO CALCIFY
- ) CALCIFICATION ZONE - MATRIX BECOMES CALCIFIED AND CHONDROCYTES DIE LEAVING BONE-LIKE TISSUE (NOT BONE YET)
- ) OSSIFICATION ZONE - OSTEOCLASTS DIGEST CALCIFIED CARTILAGE AND OSTEOBLASTS REPLACE IT W/ ACTUAL BONE TISSUE IN THE SHAPE OF CALCIFIED CARTILAGE => BONE TRABECULAE
FUSION OF EPIPHYSIS
AT FULL BONE LENGTH CELLS IN EPIPHYSEAL CARTILAGE STOP PROLIFERATING AND BONES OF DIAPHYSIS AND EPIPHYSIS THEN BECOMES CONTINUOUS
ACHONDROPLASIA
DEFECT IN CARTILAGE FORMATION (MOST COMMON CAUSE = DWARFISM)
SALTER-HARRIS FRACTURES
INVOLVE EPIPHYSEAL PLATES (INTERFERES W/ GROWTH AND HEIGHT)
OSGOOD-SCHLATTER DISEASE
STRESS ON EPIPHYSEAL PLATES IN THE TIBIA LEAD TO EXCESS BONE GROWTH AND A PAINFUL LUMP IN THE BONE
SOMATOTROPIN
PRIMARY GROWTH FACTOR THAT AFFECTS BONE GROWTH
STARTS IN THE HYPOTHALAMUS
-TROPIN = TO NOURISH/STIMULATE
HYPOTHALAMIC PITUITARY AXIS
RELEASES GROWTH HORMONE RELEASING HORMONE (GHRH) WHICH CAUSES A RELEASE OF SOMATOTROPIN FROM THE ANTERIOR PITUITARY WHICH THEN TRAVELS TO THE LIVER AND STIMULATES THE RELEASE OF NEW GROWTH FACTOR, INSULIN-LIKE GROWTH FACTOR WHICH ACTS AS A NEGATIVE FEEDBACK LOOP AND BINDS TO THE HYPOTHALAMUS TO TELL IT TO STOP RELEASING GHRH VIA SOMATOSTATIN (GROWTH HORMONE INHIBITING HORMONE) AND PROMOTES FEMUR AND MUSCLE GROWTH
GIGANTISM
EXCESSIVE GH SECRETION THAT STARTS IN YOUNG ADULTS/ADOLESCENTS
RARE, RESULTING FROM A TUMOR OF SOMATOTROPES
PITUITARY DISORDER
ACROMEGALY
EXCESSESIVE SECRETION OF GH IN ADULTS AS A RESULT OF A BENIGN PITUITARY TUMOR
CLINICAL SIGNS -
1.) OVERGROWTH OF EXTREMITIES
2.) SOFT TISSUE SWELLING
3.) ABNORMALITIES IN JAW STRUCTURE - MAX/MAN PROGNATHISM (ONLY AFFECTED DUE TO 2˚ CARTILAGE)
4.) CARDIAC DISEASE
CAUSES HYPERGLYCEMIA - NO EFFECTS ON HEIGHT B/C EPIPHYSEAL PLATES ARE ALREADY CLOSED
ESTROGEN’S ROLE IN CLOSURE OF EPIPHYSEAL PLATES DURING EARLY SEXUAL MATURATION
ESTRADIOL-17β (E2) HAS AN INDIRECT EFFECT ON THE E2/α-ESTROGEN RECEPTOR WHICH STIMULATES GROWTH HORMONE SECRETION AND YIELDS INCREASED LONGITUDINAL BONE GROWTH
ESTROGEN’S ROLE IN CLOSURE OF EPIPHYSEAL PLATES DURING LATE SEXUAL MATURATION
E2 HAS A DIRECT EFFECT ON THE E2/α-ESTROGEN RECEPTOR WHICH INHIBITS CHONDROCYTE PROLIFERATION AND YEILDS A CESSATION OF LONGITUDINAL BONE GROWTH
EPIPHYSEAL PLATE CLOSURE IN MALES
ANDROSTENEDOINE ————-> ESTRONE (LESS POTENT)
TESTOSTERONE ————> ESTRADIOL
SAME PROCESS AS FEMALES BUT GROWTH OCCURS FOR LONGER PERIODS OF TIME IN MALES
BONE RESORPTION ESSENTIAL POINTS
RESORPTION BAYS - GROOVES FORMED BY OSTEOCLASTS AS THEY BREAK DOWN BONE MATRIX
RESORPTION INVOLVES OSTEOCLAST SECRETION OF
- ) LYSOSOMAL ENZYMES THAT DIGEST ORGANIC MATTER
- ) HCL THAT CONVERTS CA2+ SALTS INTO SOLUBLE FORM
- ) BROKEN DOWN PRODUCTS ARE ENDOCYTOSED AND RELEASED INTO INTERSTITIAL FLUID/BLOOD
BONE RESORPTION MECHANISM
- ) CA SYNTHESIZES HCO3- FROM CO2 AND H2O
- ) HCO3- IS CHANNELED TO THE SITE OF CACO3 SYNTHESIS
- ) POLYPHOSPHATE IS FORMED AND STORED W/IN CELL VESICLES AND NEUTRALIZED BY METAL IONS
- ) POLYPHOSPHATE IS RELEASED INTO EXTRACELLULAR SPACE AND HYDROLYZED BY ALKALINE PHOSPHATE
- ) ORTHOPHOSPHATE AND CA2+ (COMPONENTS OF SYNTHESIS OF HAP) ARE LIBERATED TO FORM CA5(PO4)3(OH)
- ) DEPOSITION OF HAP PROCEEDS ONTO CACO3 CRYSTALS
A DIET RICH IN…
PROTEIN, VITAMIN C/D/A, CALCIUM, PHOSPHORUS, MAGNESIUM, AND MANGANESE IS REQUIRED FOR BONE DEPOSITION
(1) OSTEOID SEAM AND (2) CALCIFICATION FRONT
- ) UNMINERALIZED BAND OF BONE MATRIX
2. ) BETWEEN THE OSTEOID SEAM AND THE OLD MINERALIZED BONE
BONE GROWTH CESSATION
AT AGE…
21 FOR MALES
18 FOR FEMALES
HORMONAL CONTROL OF BONE AND CALCIUM HOMEOSTASIS
- ) PARATHYROID HORMONE - (PTH) INCREASES THE NUMBER AND ACTIVITY OF OSTEOCLASTS, PROMOTES RECOVERY OF CALCIUM FROM URINE AND PROMOTES FORMATION OF CALCITRIOL (PART OF PARAFOLLICULAR TISSUE - CELLS IN THE THYROID OUTSIDE OF THE FOLLICULAR GLAND)
- ) CALCITONIN - INHIBITS ACTIVITY OF OSTEOCLASTS, SPEEDS UP CALCIUM ABSORPTION FROM BLOOD AND ACCELERATES CALCIUM DEPOSITION BY BONES
- ) VITAMIN D - CALCIUM AND PHOSPHATE ABSORPTION AND REABSORPTION, SIMILAR STRUCTURE TO ANDROGEN AND ESTROGEN
VITAMIN D
ACTIVATED BY THE RUPTURE OF THE BETA RING BY UV LIGHT FROM THE SUN
ONCE ACTIVATE THE MOLECULE IS MOVED TO THE LIVER, TRANSFORMED AND MOVED TO THE KIDNEY WHERE IT IS OFFICIALLY ACTIVATED AND ALLOWED TO ACT ON VARIOUS TISSUES
INTESTINES - INCREASES DIET CALCIUM AND PHOSPHATE ABSORPTION
KIDNEYS - DECREASES CALCIUM LOSS IN THE URINE
BONE - INCREASES CALCIUM MOBILIZATION FROM THE BONE
VITAMIN D ENDOCRINE ACTIONS
INTESTINAL CALCIUM TRANSPORT BONE METABOLISM RENAL CALCIUM ABSORPTION BLOOD PRESSURE INSULIN SECRETION
VITAMIN D AUTOCRINE/PARACRINE ACTIONS
INHIBITION OF CELL PROLIFERATION
PROMOTION OF CELL DIFFERENTIATION
IMMUNE REGULATION
PTH BALANCE
INCREASED PTH INHIBITS RELEASE FROM OSTEOBLASTS/STROMAL CELLS OF OPG THAT INHIBITS OSTEOCLASTS
INCREASE PTH => INCREASED RANKL AND DECREASED OPG => INCREASED OSTEOCLASTS => INCREASED CALCIUM IN THE BLOOD
HORMONAL REGULATION OF CALCIUM
RISING CALCIUM LEVELS TRIGGER THYROID TO RELEASE CALCITONIN (INHIBITS BONE RESORPTION AND STIMULATES CALCIUM SALTS TO BE DEPOSITED IN THE BONE)
FALLING CALCIUM LEVELS SIGNAL PTG TO RELEASE PTH (SIGNALS OSTEOCLASTS TO DEGRADE BONE MATRIX AND RELEASE CALCIUM INTO THE BLOOD)
BONE COMPOSITION
60% INORGANIC MATERIAL - FORMED FROM HAP
25% ORGANIC MATERIAL - COMPOSED OF TYPE I COLLAGEN AND GF
15% WATER
BONE REMODELING CYCLES
COUPLED AND BALANCED - OSTEOCLAST ACTIVITY = OSTEOBLAST ACTIVITY
COUPLED AND UNBALANCED - OSTEOCLAST ACTIVITY > OSTEOBLAST ACTIVITY
UNCOUPLED - OSTEOCLAST ACTIVITY»_space; OSTEOBLAST ACTIVITY
MECHANICAL STRESS ON BONE
INCREASES OSTEOBLAST ACTIVITY
OSTEOPOROSIS
BONES BECOME FRAGILE AND MORE LIKELY TO FRACTURE, BONE LOSES DENSITY (I.E. CALCIUM AND MINERALS IN THE BONE)
