Bones and Skin PDF

Integumentary System Structure of the Skin → Elephants dig holes 1.​ Epidermis (outermost layer) -​ Layer of avascular epithelial tissue 2.​ Dermis (middle layer) -​ Tough layer of vascular fibrous connective tissue 3.​ Hypodermis (subcutaneous) (innermost layer)...

Integumentary System Structure of the Skin → Elephants dig holes 1.​ Epidermis (outermost layer) -​ Layer of avascular epithelial tissue 2.​ Dermis (middle layer) -​ Tough layer of vascular fibrous connective tissue 3.​ Hypodermis (subcutaneous) (innermost layer) -​ Layer of adipose tissue Structure of the Epidermis (4 different cell types in 5 layers) 1.​ Stratum Basale -​ Deepest innermost (attached to the dermis) -​ Single row of keratinocytes (cuboidal) -​ Basal cells – Rapidly and continuously dividing cells – pushed new cells into the layers above -​ Produces dead skin and keratin -​ Includes melanocytes (melanin pigment) and tactile cells -​ Merkel cells (involvment with the nervous system = touch receptor cells) 2.​ Stratum Spinosum (AKA prickly layer) -​ 4th layer from the bottom  -​ Cuboidal cells – several layers of cells thick with a weblike system of filaments and desmosome = “prickles” OR “spiny layer” -​ Also contain dendritic cells that are able to ingest foreign substances and activate the immune system (macrophage) → Langerhans cells (LCs) are a type of dendritic cell that are part of the body's immune system and help fight infection 3.​ Stratum Granulosum (AKA granular layer) -​ 3rd layer from the bottom -​ Squamous cells – 4-6 layers thick -​ Keratinization begins here -​ Cells are far from dermal capillaries -​ They do not receive enough nutrients -​ They fill up with keratin as they die -​ Makes the skin harder and scalier – better protect the body 4.​ Stratum Lucidum (AKA clear layer) -​ 2nd layer from the bottom -​ Squamous cells – 2-3 cell layers thick made of dead and clear keratinocytes -​ These aggregate into tonofilaments -​ Thick, dead, clear, hairless areas that aggregrate into monofiilaments = tought outer layer 5.​ Stratum Corneum (AKA horny layer) -​ 5th layer - outtermost layer -​ Dead and anucleated cells (keritinocytes) – 20-30 cell layers thick -​ Thick membranes, full of keratin to protect cells underneath, we shed every 28-30 days (gets longer as we age) → we are protected by many layers of dead cells that have thick membranes and are full of keratin Strucutre of the Dermis (2 sections) -​ Connective tissue that is both Dead and anucleated cells vascular and innervated – where hair follicles begin -​ Sweat glands, hair follicles and nerves found here FUNCTION: -​ regulate temperature  -​ supply the epidermis with nutrient-saturated blood. -​ Much of the body's water supply is stored within the dermis. INCLUDE: -​ Blood vessels -​ Lymph vessels -​ Hair follicles -​ Sweat glands -​ Sebaceous glands -​ Nerve endings -​ Collagen and elastin 1.​ Papillary layer (outtermost layer) -​ Made of areolar connective tissues with a network of collagen and elastic fibers -​ Dermal papillae stck out into the epidermis above = fingerprinting -​ Dermal ridges cause ridges in the epidermis as well – enhance gripping ability -​ More loosely packed 2.​ Reticular layer (innermost layer -​ Dense fibrous connective tissue arranged irregularly -​ Network of blood vessels -​ More tightly packed THEN the Subcutis (AKA ADIPOSE TISSUE) FUNCITION: -​ an insulator, conserving the body's heat -​ a shock-absorber, protecting the inner organs. -​ It also stores fat as an energy reserve for the body. Skin Appendages 1.​ Hair = flexible strand of dead keratinized cells (hard keratin) -​ Includes eyelash, nose hair Hair Types 1.​ Vellus Hair (pale and fine) 2.​ Terminal Hair (dark and coarse) Nails = hard keratin Glands Sweat Glands (AKA Sudoriferous Glands) -​ Everywhere on the surface of the skin -​ Up to 3 million TYPES of SWEAT GLANDS: 1.​ Eccrine = everything = evaporation (water 99%)/Merocrine sweat glands -​ Most common -​ Coiled tube -​ Secretion occurs in the dermis 2.​ Apocrine = armpits → sweat glands -​ Fewer (only found in certain places on the body) -​ Secrete fat and protein which cause body odor Includes: -​ Ceruminous gland: produce earwax -​ Mammary gland:produce breast milk -​ Sebaceous gland/ Oil gland: secretes sebum which lubricates hair and skin Overall Integumentary System 1.​ Skin 2.​ Hair 3.​ Nails 4.​ Glands → Function: acts as a barrier, separating what is outside from the inside → Ability: repair quickly, regulate body temperature, respond to stimuli Layers/Stratum of the Epidermis Integumentary ​ first act of protection ​ Repairs quickly ​ Regulates body temperature ​ Repsonds to stimuli ​ Made of endothelia cells ​ Structure - outer layer epidermis - middle dermis - within layer is hypodermics  ​ Epidermis 5 layers 1.​ Stratum basale (basal layer) is the rapidly dividing cells needed for quick cell replace made of the keratinocytes ensure new epidermis is available (also have melanin and touch receptors tactile cells Merkel cells ​ The basal cells continually divide, and new cells constantly push older ones up toward the surface of the skin, where they are eventually shed. The basal cell layer is also known as the stratum germinativum due to the fact that it is constantly germinating (producing) new cells. ​ The basal cell layer contains cells called melanocytes. Melanocytes produce the skin coloring or pigment known as melanin, which gives skin its tan or brown color and helps protect the deeper layers of the skin from the harmful effects of the sun 1.​ Stratum spinosum (squamous layer) is the prickly layer for immune functions with Langerhans cells ​ The squamous cell layer is the thickest layer of the epidermis, and is involved in the transfer of certain substances in and out of the body. 1.​ Stratum granulosum - granular layer - where keratinization begins (4-6 cells thick) cells flatten while orangeades die out they fill with keratin as they die off and don’t receive enough nutrient because they are far from the dermal capillaries 2.​ Stratum lucidum - clear layer with 2-3 cells thick of dead and clear keratinocytes (aggregate into monofilaments tough outer layer 3.​ Outermost is stratum cornem is the horny layer. 10-30 layers of dead skin cells with thick membranes full of keratin to protect all of the living cells. ​ continuously shedding cell turn over occurs every 28 -30 days and gets longer with age Dermis - beneath epidermis and thickest 90% 1.​ Papillary layer that have pili sticking into the above layer can cause layering in finger tips for better grip 2.​ Regulates body temp and supply epidermis with nutrients through blood 3.​ Reticular layer (most) dense network of blood vessel to supply oxygen and nutrients and take away cell waste and transport vitamin d produced in skin 4.​ Lymph vessels for infection fighting cells of the immune system 5.​ Hair follicles tube shapes sheath that surrounds hair under skin Skin Appendages  1.​ Hair all over the body to protect body functions 2.​ Hair is hard dead keratin cells, produced by hair follicles where keratinization occurs that has a shaft but sticks out Hair shaft ​ hair matrix where cells divide ​ Erector pili produce goose bumps ​ Vellus hair - pale and fine ​ Terminal hair - dark and coarse 3 layers of hair cell 1.​ Cuticle - single layer of overlapping cells - most keratin (most inner) 2.​ Medulla - larger cells and soft keratin (middle) 3.​ Cortex - several layers of flattened cells (outside) Nails ​ hard keratin ​ Body ​ Nail matrix = growth: where cells divide and grow outward Glands ​ sweat glands - sudoriferous glands ​ 2 types Eccrine/ merocrine sweat gland (99% water) - secretion occurs in the dermis towards pore - over entire body to regulate body temp by bringing water to pores to the surface of the skin to evaporate Apocrine seat glands - secret fat and protein products produce odour (bacteria) - armpits and pubic regions Sebaceous glands/oil glands - attached to hair follicle ​ secretes sebum to soften hair and skin ​ Everywhere except for palms and soles ​ Waterproof and protects against an overgrowth of bacteria and fungi on skin Nerve endings  ​ dermis contains pain and touch receptors for brain interpretation - involuntary movements Collagen and elastin ​ protein collagen made by fibroblasts (resilience) → healing and collagen ​ Elastin for return of stretch Burn Injuries ​ local and systemic effects ​ Inflammatory response have negative effects on capillary leak, inhalation, and multiple organ failure ​ Inflammation is still requires for wound healing ​ Burns may be due to heat, freezing, electricity, chemicals, radiation or friction. ​ Fatal complications include shock, injection, electrolyte imbalances, respiratory failure ​ Psychological/emotional distress from hospitalization, scarring, and deformities ​ burn injury is dynamic process that peaks at about 3 days (process with necrosis and apoptosis) ​ Classified internationally by degree 1-3 ​ Degree 1 - superficial ​ Degree 2(a) - superficial partial ​ Degree 2(b) - deep partial ​ Degree 3 - full thickness ​ three zones of burn wounds 1.​ Zone of coagulation - focus of injury with devitalized tissue (no more blood flow) 2.​ Zone of stasis - mid to deep dermal burn with ischaemia (most challenging to treat because of potential to progress into a full thickness lesion) (apoptosis OR necrosis may contribute to tissue damage mostly here = due to limited blood supply) (inbetween) 3.​ Zone of hyperaemia/inflammation - peripheral with vasodilation, inflammatory changes without structural damage (more like first degree) 1.​ Burn Healing ​ epidermis derived from ectoderm that has regenerative properties ​ Transforming growth factor (TGF)-beta is essential for the activation and proliferation of fibroblasts during the initial stage of wound healing. (Overproduction of this growth factor causes hypertrophic scars and deformity) ​ The application of a novel nitric oxide (NO)-containing topical gel improved re-epithelization associated with the increased abundance of fibroblasts and inflammatory cells Systemic Effects = all organs ​ multiple organ and body systems effected (renal, respiratory, intestinal, immuosupression) ​ Associated with hyper metabolism then followed by catabolism due to increased oxygen consumption ​ Ischaemia triggers oxidative stress leading to the generation of molecular mediators that ultimately will cause two types of cellular damage: necrosis and apoptosis  ​ A depression of cardiac output immediately follows burn injury. As hypovolaemia ensues, diminished plasma volume and reduced venous return then contribute to a continued cardiac output ​ Major burn injury also alters the flux of calcium ions between the sarcoplas- mic reticulum and the cytoplasm Therapeutic strategies/clinical treatment: 1. Surgical intervention (early excision⁄skin grafting). 2. Volume therapy. 3. Therapy of sepsis and multi organ failure. 4. Nutrition. 5. Rehabilitation. Management of burns ​ airway main consideration is obstructed airway after swelling occurs ​ Sepsis is a major risk after any large burn because the primary barrier to microbial invasion, the skin, is lost. Malignant Melanoma - Skin cancer ​ caused by malignancy of melanocytes ​ Greater sun exposure leads to higher risk of diagnosis ​ The typical therapy for malignant melanoma is surgical excision, immunotherapy such as interleukin 2 (IL-2), gene therapy, and biochemotherapy. ​ Melanocytes in basal layer where melanin produced and packaged to the keratinocytes - provides protection of nuclei of epidermal cells by absorbing UV rays to then neutralize that generates free radicals Bones and Skeletal System Calcitonin -​ Prevents bone breakdown -​ Lowers blood calcium levels by preventing the kidneys from reabsorbing calcium -​ Blocking the breakdown of bone calcium. -​ Calcitonin may help improve bone density in patients taking corticosteroids long-term. Calcitriol -​ Increases bone breakdown -​ Works for the bones = if low brings from blood (GI absorption) -​ Increases blood calcium levels by helping the gut absorb calcium from food and preventing the kidneys from losing calcium. -​ Calcitriol is also known as active vitamin D PTH -​ Controls level of calcium in the blood – acting on bone to increase movement of calcium into the blood -​ Works for the blood = if low in blood brings from bones The Skeletal System CONSISTS OF: ​ Bones (206 in an adult) ​ Cartilage ​ Joints ​ Ligaments → 20% of body mass BONES 1.​ Axial (head and torso) Bones -​ Found in the head and torso -​ Skull, vertebral column, thoracic cage 2.​ Appendicular Bones -​ Found in the appendages/limbs -​ Arms and legs, pelvis, shoulders AXIAL BONES 1.​ Skull -​ Contains 22 bones -​ Cranial bones – protect the brain  -​ Facial bones – structure to the face -​ Flat bones – connected at sutures -​ Cranium consists of a vault (area where brain sits) and a base → altogether there are 8 CRANIAL BONES Foramina: holes that nerves and arteries and veins pass through -​ Foramen Magnum: hole for the spinal cord AXIAL BONES – Spinal Column INCLUDES: -​ 26 irregular bones that form an S-shape -​ Supports everything from the skull to the pelvis SPINE SECTIONS → bones get larger as we go down the spine to support weight STRUCTURE of the SPINE STRUCTURE of the VERTEBRA Cervical Vertabra (C3) ​ Have a short bifid spinous process ​ These have a large vertebral foramen ​ The transverse foramen accommodates arteries Thoracic Vertebra (T9) ​ These have a long spinous process pointing down ​ Have demifacets that connect to the ribs Lumbar Vertebra (L2) ​ Have pedicies and laminae that are short and thick Axial Skeleton – THORACIC CAGE -​ Sternum -​ Ribs -​ Costal cartilage Sternum Structure RIB – Structure There are 12 pairs of ribs 1.​ True Ribs (Ribs 1-7) -​ Attach directly to the sternum vis costal cartilage -​ These get longer going from 1-7 2.​ False Ribs (Ribs 8-12) -​ RIBS 8-10: Attach indirectly to the sternum via costal cartilage to cartilage from ribs above -​ RIBS 11-12: are called floating ribs because they do not attach to the sternum in any matter -​ These get shorter going from 8-12 APPENDICULAR BONES -​ Found in the appendages/lims -​ Arms and legs, pelvis and shoulders Pectoral Gridle -​ Attaches the upper limbs to the axial skeleton Clavical  -​ Sternal end -​ Acromial end Scapula -​ Thin flat bone thoroughly triangular - superior (top) - medial/vertebral (inner) - lateral/axillary (outer) The Upper Limb -​ Arm + Forearm + Hand → ARM – ANATOMY → FOREARM – ANATOMY → HAND – ANATOMY PELVIS -​ The pelvic girdle attaches the lower limbs to the axial skeleton PELVIC GIRDLE THE LOWER LIMB THIGH + LEG + FOOT THIGH = FEMUR (the largest bone in the body) LEG = TIBIA and FIBIA FOOT = FOOT BONES → BONE Metabolism (Remodeling) REMEMBER: ​ Osteoblasts: "B" for build. ​ Osteoclasts: "C" for chew. When a Bone Breaks – General Recap of Events: ​ Bone break creates fracture hematoma ​ Osteoblasts and chondrocytes build a callus ​ Osteoclasts remove damaged bone ​ Osteoblasts build new bone → AXIAL SKELETON (central axis of a human) → APPENDICULAR SKELETON Bones ​ 206 human bones ​ Cartilage, joints and ligaments Appendicular bones Skull - mostly flat bones ​ cranial protects brain ​ Facial bones gives facial structure ​ Cavities orbital, nasal, ear canal ​ Foramina - holes that nerves and arteries and veins pass through Thoracic ​ sternum ​ True ribs (1-7) longer ​ False ribs (8-12) shorter  ​ Floating ribs (11-12) Appendicular bones ​ pectoral girdle ​ Clavicle and scapula give the shoulder ​ Scapula is flat Upper limb -arm is humerus and radial -forearm has ulna (longer) and radius ​ hand, carpels, 5 metacarpals, Pelvic girdle ​ sacrum, hip bones, ilium, ischium, pubis Thigh ​ Femur, largest bones Leg ​ fibula thin ​ Tibia Foot ​ talus and calcaneus make ankle ​ Metatarsals 5, 14 phalanges Bone Metabolism ​ remodeling ​ Osteoblasts build up bones organic and inorganic matrix by producing collagen and secrete it. Uptake calcium and phosphate from blood ​ Osteoclasts are cells that resorb bone by breaking down matrix like calcium and phosphate then release them into the blood Bones ​ modeling, which allows for the formation of new bone at one site and the removal of old bone from another site within the same bone. This process allows individual bones to grow in size and to shift in space. ​ Both genes and the environment contribute to bone health ​ The growth of the skeleton, its response to mechanical forces, and its role as a mineral storehouse are all dependent on the proper functioning of a number of systemic or circulating hormones that respond to changes in blood calcium and phosphorus. If calcium or phosphorus are in short supply, the regulating hormones take them out of the bone to serve vital functions in other systems of the body. Too many withdrawals can weaken the bone ​ Osteoporosis, the most common bone disease, typically does not manifest until late in life, when bone loss begins due to bone breakdown and decreased levels of bone formation ​ why humans have bones; ​ bony skeleton is a remarkable organ that serves both a structural function, providing mobility, support, and protection for the body, and a reservoir function, as the storehouse for essential minerals. ​ Reserve of calcium and phosphorus for nerve and muscle use and all organ functions, hormones keeps the blood in constant supply of nutrients from bones ​ Bones need to be able to perform weight bearing functions and well as draw from when needed without getting too weak, battling of function over time can weaken the bones function ​ Bones also need consistent stimulation to withstand strength otherwise like in space, the weightlessness will cause the bones to weaken ​ Dual roles of supporting and regulation of calcium and phosphorus and repair damage to skeleton and constant change ​ Uses regulatory system that involves specialized cells that communicate to respond to stimuli internally and externally, mechanical and hormonal, systemic and local. ​ how bones work; ​ bones are crystals of minerals bound to protein for strength and resilience to absorb impact without breaking ​ Made of collagen in long thin rods with three intertwined protein chains and strengthen by chemical connections ​ osteocytes - which produce chemical signals that allow the skeleton to respond to changes in mechanical loading ​ Abnormalities in the collagen scaffold can occur as a result of a genetic disorder called osteogenesis imperfecta, while the failure of mineral deposition can be the result of rickets and osteomalacia, conditions that result in marked weakening of the skeleton ​ Most bones are hollow structures in which the outer cortical bone shell defines the shape of the bone. This cortical shell is essential because it provides strength, sites for firm attachment of the tendons, and muscles and protection without excessive weight. ​ Trabecular network has two functions, providing surface for mineral exchange and maintains skeletal strength and integrity ​ Spine, ends of long bones that ae under constant stress from motion of weight bearing and will fracture due to stress ​ Cortex size might enhance when dominantly used in junction with the musculoskeletal system. Provides a lever for the muscle to move on. ​ When muscle loss happens it also affects the bone as they are integrated in function ​ The most common type of joint degeneration is osteoarthritis, a painful, degenerative condition that affects the hip, knees, neck, lower back, and/or small joints of the hand ​ Problems with any one component of this system can affect the other components. Thus, weakness of the muscles can lead to loss of bone and joint damage, while degeneration of the joints leads to changes in the underlying bone, such as the bony spurs or protuberances that occur in osteoarthritis ​ how bones change during life; ​ change in size, shape, and position by modelling (formed then broken down at a different site) and remodelling (cellular removal and replacement of bone) ​ Resorption (the process of breaking down bone), particularly on the surface of trabecular bone, can supply needed calcium and phosphorus when there is a deficiency in the diet or for the needs of the fetus during pregnancy or an infant during lactation. ​ When calcium and phosphorus supplies are ample the formation phase of remodeling can take up these minerals and replenish the bank ​ Osteocytes are the most numerous cells in bone and are extensively connected to each other and to the surface of osteoblasts by a network of small thin extensions. This network is critical for the ability of bone to respond to mechanical forces and injury. ​ Inadequate bone matrix formation also occurs in osteoporosis, particularly in the form of osteoporosis produced by an excess of the adrenal hormones called glucocorticoid-induced osteoporosis. This form of osteoporosis differs from primary osteoporosis and most other forms of secondary osteoporosis because with glucocorticoid-induced osteoporosis inhibition of bone formation is the dominant mechanism for weakening of the skeleton. ​ The osteoclasts remove bone by dissolving the mineral and breaking down the matrix in a process that is called bone resorption. ​ Excessive bone breakdown by osteoclasts is an important cause of bone fragility not only in osteoporosis, but also in other bone diseases such as hyperparathyroidism, Paget’s disease, and fibrous dysplasia ​ During the reversal phase the resorbed surface is prepared for the subsequent formation phase, in part by producing a thin layer of protein, rich in sugars, which is called the  cement line and helps form a strong bond between the old bone and the newly formed bone ​ Since remodeling serves both the structural and metabolic functions of the skeleton, it can be stimulated both by the hormones that regulate mineral metabolism and by mechanical loads and local damage acting through local factors. ​ what keeps bones healthy; ​ Calcium regulating hormones - 1) parathyroid hormone or PTH, which maintains the level of calcium and stimulates both resorption and formation of bone; 2) calcitriol, the hormone derived from vitamin D, which stimulates the intestines to absorb enough calcium and phosphorus and also affects bone directly; and 3) calcitonin, which inhibits bone breakdown and may protect against excessively high levels of calcium in the blood. ​ PTH released from glands adjacent to thyroid gland to control level of calcium in the blood and can act on bone to increase movement of Ca from bone to blood ​ Calcitriol acts on intestine to increase absorption of Ca and Phosphorus needed for skeletal bones. Vitamin D made in the skin is required and deficiency can lead to disease or defective mineralization ​ Calcitonin produced by cells of thyroid glands can block bone breakdown by inactivating osteoclasts and can be used as a drug for bone disease. ​ Estrogen - acts on both cells and inhibit bone breakdown at all stages of life and contribute to bone growth during development ​ GFSH - essential for bone growth ​ what causes bone disease, including the most common form, osteoporosis; and ​ Bone disease, including osteoporosis (the most common form), is often caused by imbalances in bone remodeling where bone resorption outpaces bone formation. Factors contributing to bone disease include aging, hormonal changes (especially decreased estrogen), poor nutrition (low calcium or vitamin D), inactivity, genetics, and certain medications or medical conditions. ​ the future of bone biology and what it means for preventing and treating bone disease. ​ Future advancements in bone biology focus on better understanding molecular pathways involved in bone remodeling, identifying biomarkers for early detection, and developing targeted therapies. Strategies include enhancing bone regeneration, preventing bone loss, and exploring novel medications to strengthen bone health. General Physiology of Bones Bones are living, dynamic tissues that perform structural and metabolic functions. They provide mobility, support, and protection, house bone marrow, and act as reservoirs for calcium and phosphorus. Form and Function Bones are composed of a dense outer layer (cortical bone) and a spongy inner layer (trabecular bone). They support the body, protect organs, enable movement via muscles, and serve as a site for hematopoiesis (blood cell production). Location and Types 1.​ Long Bones: Found in limbs (e.g., femur, humerus) for weight-bearing and movement. 2.​ Short Bones: Found in wrists and ankles for stability and flexibility (e.g., carpals). 3.​ Flat Bones: Found in the skull, ribs, and sternum for protection and muscle attachment. 4.​ Irregular Bones: Found in the vertebrae and pelvis for varied support and protection roles. 5.​ Sesamoid Bones: Embedded in tendons (e.g., patella) to reduce stress and friction. Bones play a vital role in maintaining homeostasis by: 1.​ Mineral Storage and Release: They store calcium and phosphorus, releasing them into the bloodstream to regulate levels essential for nerve and muscle function. 2.​ Blood Cell Production: Red and white blood cells, along with platelets, are produced in the bone marrow, supporting oxygen transport and immune defense. 3.​ Energy Storage: Yellow marrow stores fat, serving as an energy reserve. 4.​ pH Regulation: Bones can absorb or release alkaline salts to maintain blood pH balance. Structure and Movement: Bones provide a framework for the body, protect organs, and work with muscles to facilitate movement. Bone Remodeling: A continuous cycle where osteoblasts build new bone, and osteoclasts resorb old bone, allowing for growth, repair, and mineral regulation. Calcium Homeostasis: Bones act as reservoirs for calcium and phosphorus, releasing or storing them as needed to maintain blood levels. Adaptation: Bones strengthen or weaken based on mechanical stress and hormonal signals. Deep Explanation of Bone Remodeling Bone remodeling is a continuous process of renewal involving resorption (removal of old bone) and formation (deposition of new bone). This process maintains bone strength, adapts bones to mechanical stress, and regulates calcium and phosphate levels in the blood. Key Cells Involved: 1.​ Osteoclasts: ○​ Specialized cells that break down old bone by dissolving the mineral matrix and degrading collagen. ○​ Release calcium and phosphate into the bloodstream, aiding in mineral homeostasis. 1.​ Osteoblasts: ○​ Build new bone by secreting collagen and promoting mineral deposition. ○​ Some osteoblasts become embedded in the matrix, transforming into osteocytes. 1.​ Osteocytes: ○​ Mature bone cells embedded in bone matrix. ○​ Act as mechanosensors, detecting mechanical stress and signaling to other cells to initiate remodeling. Phases of Bone Remodeling: 1.​ Activation: ○​ Signals (mechanical stress, hormones like parathyroid hormone) activate osteoclasts. 1.​ Resorption:  ○​ Osteoclasts form resorption pits on bone surfaces by dissolving bone minerals and breaking down collagen. 1.​ Reversal: ○​ Osteoclast activity ceases, and osteoblasts are recruited to the resorbed area. 1.​ Formation: ○​ Osteoblasts lay down new collagen matrix (osteoid), which mineralizes to form new bone. 1.​ Resting: ○​ The new bone surface becomes quiescent until the next remodeling cycle. Regulation: ​ Hormones: ○​ Parathyroid hormone (PTH) stimulates osteoclast activity during low calcium levels. ○​ Calcitonin and estrogen inhibit excessive resorption. ○​ Vitamin D enhances calcium absorption and bone mineralization. ​ Mechanical Stress: ○​ Weight-bearing exercises stimulate osteocytes, leading to increased bone formation. Clinical Significance: ​ Imbalances in remodeling can lead to osteoporosis (increased resorption) or osteopetrosis (excessive formation). ​ Remodeling is crucial for repairing microdamage and adapting bones to physical activity.