Patho Final

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Disorders of the Musculoskeletal System BONE CELLS 1. Osteoblasts a. Major bone-forming cell b. Becomes osteocytes Osteoclasts c. Cells which break down bone 2. Osteocytes a. Trapped osteoblasts; maintain the bone matrix 3. Osteoclasts a. Cells which break down bone b. Macrophage lineage 4. Osteogenic cells a. Undifferentiated cells that turn into osteoblasts b. Active during normal growth c. Activated in adult with healing of fractures/injuries Osteoblasts Responsible for shape and structure of the bone o Secrete collagen o Produce osteocalcin & synthesize osteoid o Cause calcium salts & phosphorus from blood to precipitate to bone matrix (mineralization of bone) o Signal osteoclast activity (through RANKL) Respond to parathyroid hormone Secrete Type I collagen for mineralization of bone Alkaline phosphatase is contained in osteoblasts & secreted during osteoblastic activity Osteoblasts also have estrogen receptors o Estrogens can increase osteoblastic activity & collagen & bone matrix production Osteocytes Transformed osteoblast that are surrounded in osteoid as it hardens from deposited minerals Synthesize matrix molecules for bone calcification Osteocytes maintain bones o Play a role in controlling extracellular concentration of calcium & phosphate o Directly stimulated by calcitonin & inhibited by Parathyroid hormone (PTH) Osteoclasts Secrete bone-reabsorbing enzymes, which digest bone matrix o Phagocytic! Like macrophages… o Contain lysosomes filled with hydrolytic enzymes Calcitonin signals osteoclast to dis-engage

Transcript of Patho Final

Disorders of the Musculoskeletal System BONE CELLS 1. Osteoblasts a. Major bone-forming cell b. Becomes osteocytes Osteoclasts c. Cells which break down bone Osteocytes a. Trapped osteoblasts; maintain the bone matrix Osteoclasts a. Cells which break down bone b. Macrophage lineage Osteogenic cells a. Undifferentiated cells that turn into osteoblasts b. Active during normal growth c. Activated in adult with healing of fractures/injuries

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Osteoblasts Responsible for shape and structure of the bone o Secrete collagen o Produce osteocalcin & synthesize osteoid o Cause calcium salts & phosphorus from blood to precipitate to bone matrix (mineralization of bone) o Signal osteoclast activity (through RANKL) Respond to parathyroid hormone Secrete Type I collagen for mineralization of bone Alkaline phosphatase is contained in osteoblasts & secreted during osteoblastic activity Osteoblasts also have estrogen receptors o Estrogens can increase osteoblastic activity & collagen & bone matrix production Osteocytes Transformed osteoblast that are surrounded in osteoid as it hardens from deposited minerals Synthesize matrix molecules for bone calcification Osteocytes maintain bones o Play a role in controlling extracellular concentration of calcium & phosphate o Directly stimulated by calcitonin & inhibited by Parathyroid hormone (PTH) Osteoclasts Secrete bone-reabsorbing enzymes, which digest bone matrix o Phagocytic! Like macrophages o Contain lysosomes filled with hydrolytic enzymes Calcitonin signals osteoclast to dis-engage o Sparing loss of calcium from bone Osteoclasts also have estrogen receptors o Estrogens can inhibit their recruitment & decreases osteoclastic activity

BONE MATRIX 1. 2. 3. Collagen fibers a. Make up bulk of bone matrix Proteoglycans a. Strengthen bone and assist bone calcium deposition Glycoproteins a. Sialoprotein, osteocalcin, bone albumin, alpha-glycoprotein b. Control collagen interactions that lead to fibril formation Bone mineralization a. Calcium and phosphate

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BONE TISSUE Compact (cortical) bone o 85% of the skeleton o Haversian system Haversian canal, lamellae, lacunae, osteocyte, and canaliculi Spongy (cancellous) bone o Lack haversian systems o Trabeculae Periosteum

LONG BONES 1. 2. 3. 4. 5. Diaphysis Metaphysis Epiphysis a. Epiphyseal plate Medullary cavity Endosteum

BONE RESORPTION CYCLE Human body is constantly removing old bone & replacing it with new bone o Called "bone turnover To perform bone turnover, your bone needs o Minerals (calcium and phosphorus) o Bone protein matrix o Osteoclasts o Osteoblasts

REGULATION OF BONE RESORPTION 1. Parathyroid Hormone (PTH) a. Increase recruitment & activity of osteoblasts and osteoclasts b. Promotes release of calcium from bone c. If PTH secretion is too high, there is an acceleration of the bone turnover Calcitonin a. Secreted by Para-follicular cells of thyroid gland. b. Inhibits release of calcium from bone

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*PTH & Calcitonin have opposite effects on Calcium levels 3. Vitamin D a. Vitamin D tends to increase recruitment of osteoclasts b. Plays a part in mineralization of bone matrix. c. Lack of Vitamin D results in osteomalacia (impaired mineralization) d. Too much Vitamin D entails bone loss Estrogen a. Increases osteoblast activity/decreases osteoclast activity

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COMPACT VS CANCELLOUS BONE Compact Bone o More dense o Exterior portion of bone Cancellous Tissue o Spongy tissue o Interior portion of bone, more vascular

Which heals faster? Cancellous Tissue LIGAMENTS & TENDONS Tendons o Muscle to bone Ligaments o Bone to bone

STRAINS Tearing or overstretching of muscle or tendons Overstretching or tears of ligament structures DISLOCATIONS-look at picture ROTATOR CUFF INJURIES Rotator cuff made up of 4 muscles & their tendons These combine to form a "cuff" over head of humerus Rotator cuff helps to lift & rotate arm & stabilize ball of shoulder within joint

FRACTURES Break in continuity of bone Pathologic o Break at site of preexisting abnormality Usually osteoporosis, cancer, Pagets disease, infection, metabolic bone disorders Injurious/trauma- trauma to bone Stress fractures (repeated strain) o Fatigue- abnormal stress or torque applied to bone with normal ability to deform & recover New activities: jogging, dancing, skating o Insufficiency or fragility- bones without normal ability to deform & recover from normal weight-bearing activity By force that wouldnt normally produce fracture Arthritis, rickets, Pagets disease

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Linear a. Runs parallel to axis of bone 2. Oblique a. Occurs at oblique angle to shaft of bone 3. Spiral a. Encircles bone b. Twisting injury c. Torque injury d. Unstable and may move after reduction 4. Transverse (closed) a. Straight across bone b. Usually simple to reduce 5. Comminuted a. Bone broken into >2 pieces b. Probably needs surgery 6. Greenstick a. Torus or buckle fracture b. Cortex buckles but does not break c. Typically in children d. Incomplete fracture e. May be parallel to bone 7. Bowing a. Longitudinal force applied to bone b. Common in children c. Involves tibia/fibula or radius/ulna i. One bone in pair breaks and forces bows other bone 8. Open Fracture a. Open to environment b. Increased risk for infection c. Increased bleeding 9. Compression a. Usually in vertebrae b. Can be due to osteoporosis 10. Impacted a. Fragments wedged together

HEALING OF FRACTURES Direct or primary healing o Similar to intramembraneous bone formation when adjacent bones cortices contact one another o Most often with surgical fixation o No callus formation Indirect or secondary healing o Similar to endochondral bone formation o Involves formation of callus & remodeling of solid bone 1. 2. Inflammatory phase a. Hematoma formation Reparative Phase a. Cell proliferation/callus formation b. Ossification Remodeling

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Inflammatory Phase: HEMATOMA FORMATION 48 - 72 hours (Inflammatory Phase) o Torn vessels in bone & soft tissues forms hematoma o Fibroblast arrives at the site of injury Initiates healing process Fibrin meshwork forms Granulation tissue begins to form Reparative Phase: CELL PROLIFERATION & CALLUS FORMATION nd th 2 - 6 week of healing (Reparative Phase) o Osteoblast & chondrobalst differentiate (periosteum) o Proteins produced by osteoblasts & chondroblasts begin to consolidate into what is known as cartilogenous soft callus o Ossification Begins Bone begins to calcify Mature bone replaces soft callus (Bony Callus) Fracture completely bridged, ends firmly united May remove cast at this point Remodeling Phase Resorption of excess bony callus by osteoclasts Directed by weight bearing Occurs after healing process HEALING TIMES 1. 2. 3. Children a. 4-6 weeks Adolescents a. 6-8 weeks Adults a. 10-18 weeks

FACTORS INFLUENCING BONE HEALING Systemic Factors o Age o Nutrition o Systemic Disease o Hormones Local Factors o Type of bone o Degree of trauma o Vascular injury o Degree of immobilization o Intraarticular fractures o Separation of bone ends o Infection/ local pathology

COMPLICATIONS OF FRACTURES 1. 2. Infection Osteomyelitis a. Usually caused by Staphylococcus Aureus b. May be due to: Direct contamination (surgical or injury) Hematogenic source Chronic Acute infection recurs Compartment Syndrome a. Increased pressure in limited anatomic space b. Compromises circulation Result from increase pressure in the tissue compartment Compromises circulation Nerve impingement c. The 5 Ps: Pain Pallor Paresthesias Pulses Paralysis d. May require fasciotomy Osteonecrosis a. Death of a segment of bone b. Not uncommon (r/t ischemia) c. Thrombosis/emboli, vascular compression, vessel injury d. Causes/Risk factors: Long term treatments with steroids Excessive alcohol use Sickle cell disease, radiation therapy, DM, gout, atherosclerosis Dislocation or fractures around a joint

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Fat Emboli Syndrome a. Usually after fracture of long bones or pelvis Fat released by bone marrow or adipose tissue at fracture site Results in fat emboli in lungs (PE) b. Manifestations: Tachypnea Dyspnea Use of accessory muscles Wheezing Inspiratory stridor Petechial rash-neck, upper chest, shoulder, axillary and buccal membranes HA Drowsiness Irritability Memory loss Confusion Rapid pulse Apprehension Fever

BENIGN NEOPLASMS OF THE BONE 1. 2. 3. 4. Osteoma a. small bony tumor on surface of long bone Chondroma a. Hyaline cartilage tumor (hands or feet) Osteochondroma a. Most common, grows only during skeletal growth, made of bone & cartilage Giant cell tumor/osteoclastoma a. Aggressive/metastatic; knee/wrist/shoulder metaphyseal regions

METASTATIC NEOPLASMS 1. Osteosarcoma- children & elderly a. Most common malignant bone-forming tumor b. Formation of immature bone by malignant osteoblasts; aggressive & undifferentiated Ewings Sarcoma- common bone tumor in childhood a. Young males, highly malignant; immature bone marrow cells become malignant (does not make bone) b. Femur, pelvis, humerus; metastasizes fast Chondrosarcoma- middle-aged & older adults (men) a. Common primary malignant tumor of cartilage

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CARPAL TUNNEL SYNDROME swelling in compartment in wrist that contains wrist & finger muscles, nerves, & blood supply Swelling puts pressure on nerve that travels in this compartment or "tunnel Pressure on median nerve causes numbness, weakness, & pain in wrist & hand

METABOLIC BONE DISEASES Osteopenia (fewer bone cells) Condition in all metabolic bone diseases Osteomalacia (adults)/Rickets (children) Inadequate & delayed mineralization in bone Softening of bones Vitamin D, Calcium or Phosphorus deficiency Paget Disease Excess osteoclast activity Excessive & abnormal bone remodeling Repaired bone becomes vascular fibrous tissue Osteoporosis Loss of bone mass/matrix Increased risk of fractures > Caucasian > Darker skinned individuals Increased bone resorption relative to bone formation 1.5 million fractures per year r/t osteoporosis S/Sx pain & bone deformity (kyphosis), height Post-menopausal higher risk WHY? o Estrogen deficiency & other age-related causes o Glucocortocoids Pathogenesis & Severity of Osteoporosis o Loss of cancellous or trabecular bone (spongy) & compact bone can become more porous o Increased bone resorption relative to bone formation o Osteoclast precursors are stimulated by cytokines o Cytokines are held at bay by estrogen o Decrease in estrogen increases osteoclast production & stimulates cytokine activity (IL, TNF, TGF-, prostagladin, RANKL) o Severity r/t peak bone mass correlated with skin pigment, exercise, good nutrition Adequate Vitamin D & Calcium intake OPG/RANKL/RANK System Risk Factors of Osteoporosis o Female o Advanced Age o Small bone structure o Low body weight o Postmenopausal o Genetic predisposition o Sedentary lifestyle o Skin pigment - Caucasian > Darker skinned o Nutrition Calcium & Vit D deficiency

JOINTS Joint classifications based on structure Fibrous Joins bone to bone o Suture, syndesmosis, gomphosis Cartilaginous Symphysis & synchondrosis Synovial Uniaxial, biaxial, or multiaxial Joint capsule, synovial membrane, joint cavity, synovial fluid, articular cartilage

OSTEOARTHRITIS- Degenerative Joint Disease Common disorder of synovial joints o Disease of use & abuse increases with age Loss & damage of articular cartilage, osteophytosis, subchondral bone changes, mild synovitis, & thickening of joint capsule Secondary to injury/inflammation, cytokine release o Exact etiology unknown- involves genetic alterations & metabolic disorders Proteases produced potentially destructive to joint tissues with loss of proteoglycans Articular cartilage broken down & lost with narrowing of joint space & possible bone spurs o Bone rubs against bone which causes further damage (erosion) Risk Factors of Osteoarthritis o Genetic predisposition o Obesity o Athletes o Aged o > 3:2

ANKYLOSING SPONDYLITIS Chronic autoimmune inflammatory arthropathy Rheumatic disease causing stiffening & fusion of spine & sacroiliac joints o Can cause inflammation of eyes, lungs, & heart valves Excessive bone formation at enthesis o Fibrosis, ossification, & joint fusion Genetic marker- HLA-B27 misfolds

RHEUMATOID ARTHRITIS Proliferative synovitis r/t chronic systemic autoimmune inflammatory disease Joint swelling , tenderness, destruction of synovial joint spreading to articular cartilage, fibrous joint capsule, & surrounding ligaments & tendons o Leads to disability & premature death > 3:1 Genetic predisposition but exact etiology unknown Affects ~1% of population; increases with age RF (rheumatoid factor) present in 80% of RA patients; ACPA more sensitive o RF + IgG = inflammatory response o Autoantibody which reacts with IgG

RA Pathogenesis o T-cell mediated response T cells express RANKL promoting osteoclast formation & boney erosion o Cartilage damage due to Activated neutrophils & other cells in synovial fluid degrade surface of articular cartilage Inflammatory cytokines induce enzymatic breakdown cartilage & bone T cells interact with synovial fibroblasts converting synovium into pannus Destruction of articular cartilage & bone erosion Pannus limits movement of joint Swan neck deformity Boutonnires thumb Ulnar deviation Evaluation o Four or more of the following: Morning joint stiffness lasting at least 1 hour Arthritis of three or more joint areas Arthritis of hand joints Symmetric arthritis Rheumatoid nodules Abnormal amounts of serum rheumatoid factor Radiographic changes

GOUT Syndrome caused by incomplete purine metabolism Uric acid is end product of purine synthesis Increased uric acid (hyperurecemia) o Overproduction of purines o Decreased salvage of free purines o Increased cell turnover (augmented breakdown of purines)- excessive production of uric acid o Decreased urinary secretion of uric acid (90% cases) Overload of uric acid in the body Uric acid is end product of purine synthesis Increased uric acid: o Overproduction of purines o Increased cell turnover (augmented breakdown of purines) o Decreased urinary secretion of uric acid Uric acid crystallizes & deposits in connective tissues o Form tophi- small white nodules Crystallization in synovial fluid causes acute, painful inflammation or gouty arthritis o Synovial fluid poor solvent for uric acid Precipitate in joints especially great toe (podagra) causing joint damage & pain Uric acid crystals tend to precipitate at lower temperatures Trauma promotes precipitation

FIBROMYLAGIA Widespread musculoskeletal pain or aches accompanied by fatigue, sleep, memory & mood issues (depression & anxiety) Believe fibromyalgia amplifies painful sensations by affecting way brain processes pain signals Symptoms begin after physical trauma, surgery, infection or significant psychological stress, or with no precipitating event Affects women more than men & runs in families May also have headaches, TMJ, IBS, SLE No cure but may be able to control symptoms o Medications, exercise, relaxation, stress-reduction NEUROLOGICAL DISORDERS FUNCTIONS OF THE NERVOUS SYSTEM Communication & coordination o Sensory input Gathering information To monitor changes occurring inside & outside the body (changes = stimuli) o Integration Process & interpret sensory input & decide if action is needed o Motor output Response to integrated stimuli Response activates muscles or glands

STRUCTURAL CLASSIFICATION OF NERVOUS SYSTEM Central Nervous System (CNS) o Brain & spinal cord o Protected by skull & vertebrae Peripheral Nervous System o Nerves outside brain & spinal cord o Input-output system for relaying information to CNS Cells:neurons & supporting cells

NERVOUS TISSUE: NEURONS Nerve cells o Specialized cells that transmit messages o Major regions of neurons Cell body nucleus & metabolic center of cell Processes fibers that extend from cell body Dendrites - carry impulses towards cell Axon - carry impulses away from cell Neurons Most found in CNS o Gray matter cell bodies & unmylenated fibers o Nuclei clusters of cell bodies within white matter of CNS Ganglia collections of cell bodies outside CNS Sensory (afferent) neurons o Carry impulses from sensory receptors Motor (efferent) neurons o Carry impulses from CNS

FUNCTIONAL CLASSIFICATION OF NEURONS Interneurons (association neurons) o Found in neural pathways in CNS o Connect sensory & motor neurons

HOW NEURONS FUNCTION Irritability ability to respond to stimuli Conductivity ability to transmit an impulse Plasma membrane is polarized at rest Depolarization a stimulus depolarizes neurons membrane & initiates action potential o Deploarized membrane allows sodium (Na+) to flow inside membrane o Potassium ions rush out of neuron after Na ions rush in, which repolarizes membrane Sodium-potassium pump restores original configuration

AXON & NERVE IMPULSES Action potential end in axonal terminals Axonal terminals contain vesicles with neurotransmitters Axonal terminals are separated from the next neuron by a gap o Synaptic cleft gap between adjacent neurons Neurotransmitter Post-synaptic receptors SYNAPTIC TRANSMISSION Neurotransmitters o CNS o PNS Serotonin Dopamine Norepinephrine Epinephrine Acetylcholine GABA Glutamate Glycine

NERVE TISSUE: Support Cells (Neuroglia or Glia) Astroglia o Links neurons & blood vessels & forms barrier between capillaries & neurons o Maintains Blood Brain Barrier o Controls chemical environment of brain (CNS) Oligodendroglia o Forms myelin in the CNS Microglia o Phagocytic cells Ependymal cells o Lining of neural tube

PNS SUPPORTING CELLS Satellite Cells o Layer of cells separating ganglia from other tissues o Satellite cells secrete a basement membrane that protects cell body from diffusion of large molecules Schwann Cells o Wraps around axon to form myelin sheath like a jelly roll o Nodes of Ranvier Gaps in myelin sheath along axon Increases saltatory conduction NEUROGLIA VS NEURONS Neuroglia divide Most brain tumors are gliomas & involve neuroglia cells, not neurons o Consider role of cell division in cancer! Support neurons Maintain Blood-Brain Barrier Produce myelin sheath (NEURONS) Neurons do not divide Afferent sensory Efferent motor Sent signals/impulses via: o Presynaptic neuron o Release neurotransmitter o Postsynaptic receptors Blood Brain Barrier protect neurons Myelin sheath important for speed of transmission DISORDERS OF BRAIN FUNCTION MECHANISMS OF BRAIN INJURY Brain protected from external forces by: o Skull o Meninges o Cerebrospinal fluid (CSF) Autoregulation Metabolic stability required by its electrically active cells maintained by: o Blood-brain barrier o Mechanisms that ensure its blood supply Primary Injury o Global cerebral ischemia occurs commonly in patients who have a variety of clinical conditions: Brain injury Cerebrovascular Accident (CVA) or Stroke Ischemic Hemorrhagic Seizures Indirect hypoxic: Cardiac arrest Shock Asphyxia

Pathways of Secondary Injury: o Glutamate efflux into extracellular compartment Results in increases in intracellular Calcium o Inflammation influx of cytoxins & edema Mechanisms of Brain Injury Pathways of Secondary Injury o Role of Inflammation Cerebral ischemia leads to inflammation Migration of peripheral leukocytes into brain & activation of microglia Release of cytokines (interleukin [IL]-1, tumor necrosis factor a [TNF-a]) Breakdown of the blood-brain barrier (BBB) Culminates in edema formation Pathways of Injury: o Cerebral Edema Vasogenic Edema Integrity of blood-brain barrier disrupted allowing fluid to escape into interstitial spaces that surrounds brain cells Cytotoxic Edema Swelling of brain cells due to an increase in fluid in the intracellular space Results in increase in intracranial pressure

INCREASED ICP Prolonged pressure >15mmHg Common pathway or end-point of brain injury Normal 5 to 15 mm Hg Caused by increase in intracranial content o Brain tissue o Blood o CSF Brain tissue volume o Cerebral edema o Brain tumor CSF o Hydrocephalus Blood volume increase / vasodilation in the brain o Acidosis o Hypercapnia o Cerebral bleeding

HYDROCEPHALUS Enlargement of CSF compartment with increase in CSF in cerebral ventricles, subarachnoid space, or both Congenital- ventricular enlargement before birth Noncommunicating within ventricular system (obstructive) o More common in children Communicating o Defective reabsorption of CSF from subarachnoid space More common in adults Acute after head injury Causes IICP

MONRO-KELLIE HYPOTHESIS Any increase in one requires compensatory decrease in another CSF is the first to compensate Can be displaced from the ventricles into spinal subarachnoid space Can undergo increased absorption or decreased production Blood volume diminishes Contained in low-pressure venous system as a means of displacing blood volume Can lead to decreased cerebral perfusion MANIFESTATIONS OF ICP- Look at powerpoint CUSHINGS TRIAD Occurs as a result of Cushing reflex When Mean Arterial Pressure is less than ICP Hypothalamus increases sympathetic stimulation Vasoconstriction, increased contractility & cardiac output Increased BP: detected by baroreceptors in carotid arteries Triggers parasympathetic & induces bradycardia Bradypnea Result of increased pressure on brainstem due to swelling, or from brainstem herniation

COMPLICATIONS OF INCREASED ICP Herniation- displacement of brain tissue

TRAUMATIC BRAIN INJURY A traumatic insult to brain possibly producing physical, intellectual, emotional, social, & vocational changes Causes: Transportation accidents Falls Sports-related event Violence

CATEGORIES OF TBI Open (penetrating, missile) trauma Injury breaks dura & exposes cranial contents to environment Causes primarily focal injuries Specific grossly visible brain lesion in precise location Closed (blunt, nonmissile) trauma Head strikes hard surface or rapidly moving object strikes head Dura remains intact & brain tissues not exposed to environment Focal (local) Injury Contusions-blood leaking from damaged vessel Hematomas Diffuse (general) brain injuries Diffuse axonal injury Concussion

FOCAL BRAIN INJURY Contusion Observable brain lesion Force of impact typically produces bleeding & contusions from small tears in blood vessels Coup injury Injury directly below point of impact Contrecoup Injury on pole opposite site of impact

HEMATOMAS Epidural Between dura & skull Subdural Between dura & arachnoid layers Intracerebral Parenchymal

SUBDURAL HEMATOMAS Acute Rapid & high mortality rate Subacute Less rapid with some improvement Chronic Symptoms occur weeks after injury Common in older patients Severing of bridging veins

DIFFUSE BRAIN INJURY Diffuse axonal injury (DAI) Shaking, inertial effect Acceleration/deceleration Axonal damage Shearing, tearing, or stretching of nerve fibers Severity corresponds to amount of shearing force applied to brain & brain stem Categories: Mild concussion Classical concussion Mild, moderate, & severe diffuse axonal injuries (DAI) Mild Concussion Temporary axonal disturbance causing attention and memory deficits but no loss of consciousness I: confusion, disorientation, & momentary amnesia II: momentary confusion & retrograde amnesia III: confusion with retrograde & anterograde amnesia Classic Cerebral Concussion Grade IV Disconnection of cerebral systems from brain stem & reticular activating system Physiologic & neurologic dysfunction without substantial anatomic disruption

Loss of consciousness (