Physiology of Bone Dr. Ross G. Cooper Senior Lecturer Ext. 6227, Rm. 701 Perry Barr, 202 W’b Rd Division of Physiology School of Health & Policy Studies Tree diagram Skeletal system Skeleton Axial skeleton Facial bones Skull Nasal bones Bone Physiology www.ama-assn.org www.eskeletons.org FIBROUS JOINTS: Fibrous tissue - no joint cavity SYNOVIAL JOINTS: Joint cavity Bone cells • As for all connective tissue, bone consists of cells and extracellular matrix. • There are three types of cells in mature bone tissue: • Osteoblasts • Osteocytes • Osteoclasts Function • Osteoblasts and osteocytes are involved in deposition of bone matrix • Osteoblasts are located at the surface of bone tissue, whereas osteoclasts are located within the calcified matrix • Osteoclasts are involved in the resorption of bone tissue. An osteoclast cell attached to the bone surface. Where it is in contact with the bone it forms a ‘ruffled zone’ under which resorption takes place. Histology of bone tissue • Like other connective tissues, bone is a matrix containing cells as opposed to a structure made of cells • The matrix is made of hydroxyapatite which is predominately tricalcium phosphate Ca3 (PO4)2 Bone structure • A typical long bone (greater length than width) consists of the following parts: • The diaphysis. The bone’s shaft or body • The epiphyses. The distal and proximal ends of the bone • The metaphyses. Regions in a mature bone where the diaphysis joins the epiphyses • The articular cartilage. This is a thin layer of hyaline cartilage Functions of bone and the skeletal system Bone tissue and the skeletal system perform several functions: Support Protection Movement Mineral homeostasis Blood cell production Triglyceride storage Support The skeleton is a structural framework for the body supporting soft tissues and provides attachment points for the tendons of most skeletal muscles Protection The skeleton protects many internal organs from injury. For example, the skull (cranial bones) protects the brain and the vertebrae protect the spinal cord. Movement As skeletal muscles attach to bones, when muscles contract they pull on bones. Thus, muscles and bones can produce movement Mineral homeostasis Bone tissue stores important minerals, especially calcium and phosphorus. Bone releases these minerals (on demand) to different parts of the body to maintain homeostasis Hormones affecting growth • Parathyroid hormone and 1,25-dihydroxyvitamin D3 stimulate bone resorption. • Calcitonin inhibits bone resorption. Blood cell production In some bones, red bone marrow (a connective tissue) produces erythrocytes, leucocytes and platelets, via a process called haemopoiesis. Triglyceride storage • Triglycerides stored in the adipose cells of yellow bone marrow form an important energy reserve • Yellow bone marrow consists mostly of adipose cells, which store triglycerides • In the newborn, all bone marrow is red and is involved in haemopoiesis • As we age, much of the bone marrow changes from red to yellow Bone pathologies • Primary bone cancer: the cancer started in the bone. • Metastatic or secondary bone cancer: did not start in the bone but has spread to the bone from other organs. E.g. when lung cancer spreads to the bones. Primary bone cancer • Osteosarcoma: cancerous tumour of the bone itself, and it is the most common primary bone cancer. • Chondrosarcoma: cancer of cartilage cells and the second most common primary bone cancer. After age 20, the risk of developing chondrosarcoma continues to rise until reaching about 75 years. Primary bone cancer continued….. • Ewing's tumour: in long bones of the legs and arms, pelvis. • Fibrosarcoma: develop from "soft tissues" (ligaments, tendons, fat & muscle). • Giant cell tumour: affect arm or leg bones. • Chordoma: This primary tumour of bone usually occurs in the base of the skull and bones of the spine. Secondary bone cancers • Lymphoma: Non-Hodgkin lymphomas generally develop in lymph nodes but sometimes start in the bone. Primary non-Hodgkin lymphoma of bone is considered a widespread disease because multiple sites in the body are usually involved. • Multiple myeloma: Although multiple myeloma almost always starts in bones, doctors do not consider this a bone cancer because it develops from the plasma cells of the bone marrow (the soft inner part of some bones). Osteoporosis Osteoporosis, or porous bone, is a disease characterized by low bone mass and structural deterioration of bone tissue, leading to bone fragility and an increased susceptibility to fractures of the hip, spine, and wrist. Men as well as women suffer from osteoporosis, a disease that can be prevented and treated. Risk factors • Gender – women have more chance. • Age - bones become less dense and weaker with age. • Body size - Small, thin-boned women are at greater risk. • Family history - Susceptibility to fracture may be, in part, hereditary. Prevention of osteoporosis • Calcium needs change during one's lifetime. It is greater during childhood and adolescence, when the skeleton is growing rapidly, and during pregnancy and breastfeeding. Postmenopausal women and older men also need to consume more calcium. Continued… • Vitamin D plays an important role in calcium absorption from the GIT. • Exercise makes bones stronger, especially weight-bearing exercise, that forces you to work against gravity. • Smoking lowers oestrogen levels. • Medications glucocorticoids (for arthritis, asthma, Crohn's disease, lupus, and other diseases of the lungs, kidneys, and liver) can lead to a loss of bone density and fractures. Rheumatoid arthritis (RA) • Systemic disease of joints. • Inflammatory condition. • Idiopathic disease that involves immune-mediated destruction of joints. • Acute inflammation: excessive production of synovial fluid, increased blood flow, neutrophil, pain, swelling and joint stiffness. Comparison of normal joint and rheumatoid arthritic joint Pathogenesis of RA • Fibroblasts and lymphocytes are white blood cells that attack the joint. • The synovium becomes thickened and irregular. • Swelling, stiffness and pain. Drugs used to treat RA • Analgesics: these drugs are painkillers. They are useful to 'top up' the pain-relieving effects of other, more specific, drugs, e.g. Paracetamol. • Methotrexate: this drug is immunosuppressive, that is it has the effect of suppressing the immune system. • Leflunomide: this is a more recently introduced drug which is about as effective as methotrexate. Infection Types of pathogens • Bacteria Pathogens continued… • Fungi Pathogens continued… • Protozoa Spread of infection • Direct Contact Transmission (DCT): - This involves the direct contact of the person with the infected material such as touching, kissing or sexual contact. Infections can also be spread directly coming into contact with infected droplets produced during sneezing. This only occurs if the droplets are large enough to carry the infection and only travel over short distances of less than a meter. Spread continued… • Indirect contact or Vehicle Transmission (VT): - Here inanimate objects are involved in the spread of the disease and are called vehicles. Examples of vehicles include money, drinking and eating utensils, books and bedding. • • Vector Borne Transmission (VBT): - Vectors are animals that carry the infection. They can be insects, ticks, fleas and mites, but can also be dogs, cats, skunks and bats. Nature of pathogens • Toxins interfere with normal cellular functions. • Toxins from outside the body are called exogenous. • Toxins produced by microorganisms (bacteria, fungi, protozoa) are endogenous. Reversible changes to infection • Alternative metabolism – a cell uses alternative pathways, e.g. in hypoxia oxidative phosphorylation is threatened. Some tissues adapt by using glycolysis. • Altered size – hypertrophy (cell and organ enlargement). • Apotosis – reduction in numbers of cells. • Cell stress proteins – response to toxins, anoxia, high temp., trauma. • Organelle changes – e.g. more/less enzymes produced. Cell & tissue accumulations • Hydropic change – accumulation of water in the cell, e.g. kidney infection. • Fatty change – fatty deposits. The liver receives free fatty acids (ffa) from other stores. Alcohol prevents liver cells from metabolizing ffa. • Hyaline change – deposits of protein found in damaged arterioles, renal tubules, etc. Irreversible cell injury • Cell membrane ruptures. • Organelles break down. • Nucleus shrinks. • Necrosis, e.g. caseous necrosis in tuberculosis – necrotic tissue has pale, cheese-like appearance. Immune System [a] Defence System [b] Extremely adaptable [c] Generates a variety of cells and molecules Immune Response Two interrelated activities  Recognition  Response Recognition Remarkably Specific Discriminate between foreing pathogen Distinguish one pathogen from another and own cells and proteins Response Also known as effector function. Eliminate or neutralize foreign organisms. Later exposure to same foreign organism memory response heightened immune reactivity. Immunity “State of protection from infectious diseases” Immunity Specific (Aquired) Nonspecific (Innate) Nonspecific Immunity “Basic resistance to disease that a species possesses” Nonspecific Immunity Barriers Inflammatory Endocytic or Phagocytic Physiologic Anatomic Anatomic Barriers Skin Sebaceous Glands secrete sebum low pH (3-5) Inhibitory to growth of most microorganisms. Mucous membranes of the respiratory/GI/Urogenital tracts Secrete mucuc traps microorganisms and expels them by movement of celia. Physiological barriers Temperature pH Soluble factors Gastric juice acidic organisms can’t survive. Newborns less acidic gastric juice more susceptible to infections. Soluble factors Complement = serum proteins that are non active. when pathogen enters activated membrane damaging reactions clear infections Endocytic and Phagocytic Barriers Endocytosis “Macromolecules in the ECF internalized by cells” Phagocytosis “More specialised and involves plasma membranes expanding around macromolecules Specialized phagocytic cells include: monocytes, macrophages and neutrophils. Inflammatory Response Signs Redness Swelling Heat Pain Three major events (1) Vadodilation (2) Increased capillary permeability (3) Influx of phagocytic cells (chemotaxis) Specific Immunity “Reflecting the presence of a specific and functional immune system” Properties of self immunity SPECIFICITY DIVERSITY MEMORY SELF/NONSELF RECOGNITION Autoregulation of pressure in head • The normal structures within the skull have more or less stable volume. There are some variations in volume depending on the person’s activities, cardiovascular as well as pulmonary status • The skull is not a completely closed sphere, there are several openings mainly in the base of the skull. It is believed that intracranial pressure is a reflection of the atmospheric pressure which is conducted through the large neck vessels. NORMAL INTRACRANIAL PRESSURE • The normal pressure is 15 mm/Hg or 150 mm - 200 mm of water. • The intracranial pressure is closely related to brain perfusion. • The cerebral blood flow is dependent on the intracranial pressure. • For this reason the intracranial pressure needs to be maintained at a steady state. This is accomplished by dynamic equilibrium of intracranial components. Dynamics of raised intracranial pressure 1. Increase of the volume of the normal content of the intracranial cavity, as increase in the volume of CSF as in hydrocephalus, increase in the volume of the brain tissue itself as in brain oedema or increased cerebral blood volume. 2. Extra volume added to the intracranial cavity as in tumours or haematomas. Autoregulation of pressure ICP is maintained within a normal range. This is called autoregulation. If the process continues the increase in volume will be associated with gradual rise in ICP.This continues up to an ICP of about 50mm Hg when the pattern changes and the intracranial cavity loses its stretchability and behaves as a solid box. There will be steep rise in the curve and incremental rise of the intracranial pressure. Cerebral oedema Because the brain is enclosed in a rigid box, any increase in volume compresses vessels and tissue, reducing perfusion and killing the tissue. Brain oedema is caused by increased vascular pressure or increased permeability. Hypertensive crisis, concussion (mechanical damage with capillary fluid leaking into the brain). 1. Brain oedema => compresses vessels (capillaries) => reduced flow => ischemia => arteriolar dilatation => increased capillary pressure => increased oedema 2. Reduced oxygen => increased capillary permeability and shuts off sodium/potassium pump => cellular swelling Bone fractures are very painful! Types of Fractures • Simple - bone breaks cleanly and does not penetrate the skin. • Compound (open) - broken ends of bone protrude through soft tissues and the skin. • Comminuted - bone breaks into many fragments. • Compression - bone is crushed. • Depressed - broken portion is pressed inward. • Impacted - broken ends are forced into each other. • Spiral - ragged break caused by excessive twisting force. • Greenstick - Bone breaks incompletely. Vertebral fractures Advanced Osteoporosis and 'Dowager's Hump' • Loss of height • Spine deformity • Often severe pain, • Loss of mobility Pain pathway Physiology of pain • Harmful stimuli activate the peripheral endings of primary sensory neurons, called nociceptors, whose cell bodies lie in the dorsal root ganglia (DRG) of the spinal cord. • Nociceptive input is conveyed from the peripheral receptors to the central nervous system predominantly by two classes of primary afferent fibres. • Of these, the slowly-conducting, thinly-myelinated A- fibres mediate thermal and mechanical nociception whereas the non-myelinated, C-fibres are activated by a variety of high-intensity mechanical, chemical, hot and cold stimuli. Modulation of pain by drugs • Analgesics - non-steroidal Anti-inflammatory Drugs (NSAIDs, e.g. aspirin, ibuprofen), effective against pain in the extremities, headache, migraine and dental pain and are generally unsuitable for treating chronic central pain. • Anaesthetics (e.g. lidocaine) - reversibly block the generation and conduction of action potentials in primary afferent fibres. • Novel drug targets - GABA is the most prominent inhibitory neurotransmitter in the mammalian nervous system. Activation of GABAb receptors by GABA reduces nociceptive transmission in the spinal cord.