EMFS Lectures (Final) PDF
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Mansoura Faculty of Medicine
Dr Eyad Mohamed Tolba
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Summary
These lecture notes cover the anatomy and physiology of the nervous system. They detail neuron types, synapses, and the divisions of the nervous system. It also touches upon the subdivisions and functions of each. The author is a faculty member of Mansoura University.
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ILO,s By the end of this lecture, each student should be able to: 1. Describe parts and types of neurons 2. Identify the synapse (relay) 3. Mention parts of the nervous system 4. Enumerate layers of the meninges 5. Enumerate segments of the spinal cord 6. Describe a...
ILO,s By the end of this lecture, each student should be able to: 1. Describe parts and types of neurons 2. Identify the synapse (relay) 3. Mention parts of the nervous system 4. Enumerate layers of the meninges 5. Enumerate segments of the spinal cord 6. Describe a typical spinal nerve 7. List names of cranial nerves 8. Define the autonomic nervous system. 9. List divisions of the autonomic N.S. 10. Explain how sympathetic and parasympathetic systems are formed. 11. Mention functions of the sympathetic and parasympathetic systems THE NERVOUS SYSTEM Theanatomical unit of nervous system is the neuron Types of neurons: 1-Sensory neurons which receive stimuli from receptors all over the body 2-Motor neurons which send the proper impulses to the effectors e.g. muscles 3-Connector or inter neuron The Nerve Cell ( Neuron ) dendrites It is formed of : Cell body a) Cell Body contains nucleus b) Processes axon carries impulses away from cell body & dendrites carry impulses towards Axon cell body. Outside CNS axons run in groups forming different nerves of the body. Synapse (relay) Impulses can pass from one neuron to another by the meeting of the axon of one neuron with the dendrites of the other. This meeting is called synapse or relay B. ANATOMICAL ORGANIZATION OF NS Division of the nervous system:- 1) Central nervous system (CNS): * It includes the brain & the spinal cord. 2) Peripheral nervous system (PNS) : * It includes 12 pairs of cranial nerves( arise from brain) & 31 pairs of spinal nerves( arise from spinal cord). Brain THE BRAIN Formed of : Cerebrum (2 cerebral hemispheres + diencephalon) Brain stem midbrain, pons & medulla oblongata Cerebellum formed of 2 cerebellar hemispheres Commissures nerve fibers which connect the right & left parts of the CNS together Subdural space BRAIN The subarachnoid space contains the CSF In cross section, the brain shows : 1. Grey matter dark areas which contain cell bodies of neurons a) Cerebral cortex ( grey mater on surface of cerebrum) b) Nucleus ( collection of cell bodies performing same function ) 2. White mater light areas which contain nerve axons (fibers). Fibers run as tracts, bundles or fasciculi THE SPINAL CORD Spinal cord inside vertebral canal Vertebral canal Spinal cord THE SPINAL CORD Covered by 3 meninges Contains a cavity called the central canal THE SPINAL CORD (cont) The spinal cord is divided into 31 segments : 8 cervical segments 12 thoracic segments 5 lumbar segments 5 sacral segments 1 coccygeal segment the spinal cord ends at the level of Lowe border of 1st lumber vertebra. THE SPINAL CORD (cont) In cross section, it 2 dorsal horns shows : Grey mater the inner Central part. Has 2 dorsal horns canal containing sensory neurons & 2 ventral horns containing motor Grey neurons White mater commisure White mater surrounds the grey mater & contains nerve fibers which run as tracts 2 ventral horns THE PERIPHERAL NERVOUS SYSTEM Formed of : 1. Cranial nerves 12 pairs which arise from the brain 2. Spinal nerves 31 pairs which arise from the spinal cord PNS: A. CRANIAL NERVES No. Name Distribution Function I Olfactory Nose Sensory (smell) II Optic Eye Sensory (vision) III Occulomotor Ms. of eye ball Motor IV Trochlear One ms. of eye ball Motor V Trigeminal Face Mixed VI Abducent One ms. of eye ball Motor VII Facial Face Mixed VIII Auditory = Ear Sensory (hearing) Vestibulocochlear IX Glossopharyngeal Mouth and pharynx Mixed X Vagus Widespread Mixed XI Accessory Neck Motor XII Hypoglossal Tongue Motor Sensory = afferent, motor = efferent, mixed = afferent & efferent fibers Dorsal root contains Each dorsal root has sensory fibers a dorsal root ganglion Ventral root contains motor fibers The 2 roots of the spinal nerve join to form a mixed trunk Spinal nerve ( motor & sensory) Trunk (mixed) Spinal nerve (cont) The 2 roots of the spinal nerve join to Spinal n form a mixed trunk trunk ( motor & sensory) The trunk passes through intervertebral foramen & divides into 2 rami 1ry dorsal ramus & 1ry ventral ramus Autonomic nervous system THE AUTONOMIC NERVOUS SYSTEM It is the involuntary component of the nervous system which is concerned with the control of smooth muscles, heart & glands. It is formed of : 1. Sympathetic system 2. Parasympathetic system They are antagonistic yet complementary to each other as they work in harmony to accomplish the physiological needs of the body. To control muscles & glands, the autonomic nervous system has 2 sets of neurones: 1. Preganglionic neurons carry impulses from CNS to ganglia outside CNS. 2. Postganglionic neurons carry impulses from ganglia to smooth muscles & glands A ganglion is a collection of neurons cell bodies outside the CNS. In ganglia, pre & postganglionic neurons meet by forming synapses. SPINAL CORD segments Sympathetic arises from all thoracic & upper 2 lumbar segments Sympathetic arises from all thoracic & Upper 2 lumbar segments Sympathetic system Prepare the body for emergency Sympathetic N.S Characters: 1- Catabolic 2- Energy consuming 3- Mass discharge 4- Prepares body for stress 5- Increase all cardiac properties 6- No micturition or defecation Parasympathetic System Formed of : 1. Preganlionic fibers 2. Parasympathetic ganglia 3. Postganglionic fibers Preganglionic fibers arise from the CNS in 2 sites : 1. With cranial nerves 3,7,9,10. 2. From neurons of lateral horn of sacral spinal segments S 2,3,4 (Craniosacral outflow) The parasympathetic system becomes active during : Parasympathetic N.S Characters: 1- Anabolic 2- Energy building 3- No mass discharge 4- Localised action 5- Decrease all cardiac properties 6- Micturition & defecation Dr Azza Kamal بسم اهلل الرمحن الرحيم َ ُ ْ ُ ْ َ َ َ َ ْ َ َ َ َّ َ َ َّ ْ َ َ ﴿ قالوا سبحانك ال ِعلم لنا ِإال ما علمتنا َّ َ َ َ ْ َ ُ ْ َ ُ ِإنك أنت العلِيم الحكِيم ﴾ صـدق الـلـه العـظـيم Dr Eyad Mohamed Tolba DR/ EYAD MOHAMED TOLBA Associate professor of Anatomy and Embryology Mansoura Faculty Of Medicine Year Two Lead Manchester Program, Taibah University Member of ESCPR Dr Eyad Mohamed Tolba Anatomy * Def: - Anatomy (Ana- up; tomy- process of cutting) - Anatomy (Dissection) is the study of the structure of the human body and the relations of its different parts to each other. Dr Eyad Mohamed Tolba Anatomy * Anatomy is divided into: 1. Microscopic anatomy (histology): - It is the study of structures of the body that cannot be seen with naked eye. - It needs a microscope. 2. Macroscopic anatomy (Gross anatomy): - It is the study of structures of the body that can be seen with naked eye. - It needs dissection. - Gross anatomy is further subdivided into: A. Regional anatomy: - Studying the human body by dividing it into regions such as trunk, upper limbs and lower limbs. B. Systemic anatomy: - Studying the human body by dividing it into systems such as respiratory system or digestive system. Dr Eyad Mohamed Tolba Anatomy * Levels of organization : The human body is organized into six levels of organization. Chemical (atoms-molecules), cellular, tissue, organ, system, and organismal levels. Dr Eyad Mohamed Tolba Anatomy *Regions of the human body: - These regions are: Head and Neck. Trunk: thorax, abdomen and pelvis. Limbs: upper and lower limbs. Dr Eyad Mohamed Tolba Anatomical Position * Anatomical Position - Described as follows: ▪ The body stands erect. ▪ Feet together. ▪ Upper limbs are along the sides. ▪ The palms of the hands facing forward. ▪ The face directed forward. Dr Eyad Mohamed Tolba Anatomical Planes 1.The midsagittal plane: - Vertical plane dividing the body into equal right and left halves. 2. Parasagittal (paramedian) planes: - Vertical and parallel to the midsagittal plane, dividing the body into unequal right and left parts. Dr Eyad Mohamed Tolba Anatomical Planes 3. Coronal planes: - Vertical and perpendicular to the midsagittal plane, dividing the body into unequal anterior and posterior parts. Dr Eyad Mohamed Tolba Anatomical Planes 4. Transverse (horizontal) planes: - Perpendicular to the midsagittal and coronal planes, dividing the body into upper and lower parts. Dr Eyad Mohamed Tolba Anatomical Planes Dr Eyad Mohamed Tolba Body Cavities * Def: - Body cavities are spaces within the body that help to protect, separate, and support internal organs. - Bones, muscles, and ligaments separate the various body cavities from one another. Dr Eyad Mohamed Tolba * Classification: Body Cavities 1. Ventral body cavity: is subdivided into: ◊ The thoracic cavity: - Fills the chest and is subdivided into two pleural cavities and the pericardial cavity. - The pleural cavities hold the lungs. - The pericardial cavity holds the heart. ◊ The abdominopelvic cavity - Fills the lower half of the trunk and is subdivided into the abdominal cavity and the pelvic cavity. - The abdominal cavity holds digestive organs and the kidneys. - The pelvic cavity holds reproductive organs and organs of excretion. Dr Eyad Mohamed Tolba Body Cavities * Classification: 2. Dorsal body cavity: - The dorsal cavity is a smaller continuous cavity located on the dorsal side of the body. - It is subdivided into the cranial and spinal cavities. The cranial cavity: - Fills most of the upper part of the skull and contains the brain. The spinal cavity: - Very long, narrow cavity inside the vertebral column. - Contains the spinal cord. Dr Eyad Mohamed Tolba Body Cavities Body Cavities Ventral Dorsal Thoracic Abdominopelvic Cranial cavity Vertebral cavity Pleural cavity Abdominal Pericardial cavity Pelvic Dr Eyad Mohamed Tolba Anatomical Terms Related to Position Posterior Anterior Dorsal Ventral Dr Eyad Mohamed Tolba Anatomical Terms Related to Position Superior Cranial Inferior Caudal Dr Eyad Mohamed Tolba Anatomical Terms Related to Position Medial Lateral Dr Eyad Mohamed Tolba Anatomical Terms Related to Position Dr Eyad Mohamed Tolba Anatomical Terms Related to Movements Flexion Extension Dr Eyad Mohamed Tolba Anatomical Terms Related to Movements Medial Rotation Lateral Rotation Dr Eyad Mohamed Tolba Anatomical Terms Related to Movements Abduction Adduction Dr Eyad Mohamed Tolba Anatomical Terms Related to Movements Abduction Adduction Dr Eyad Mohamed Tolba Anatomical Terms Related to Movements Abduction Adduction Dr Eyad Mohamed Tolba Anatomical Terms Related to Movements Supination Pronation Dr Eyad Mohamed Tolba Anatomical Terms Related to Movements Inversion Eversion Dr Eyad Mohamed Tolba Anatomical Terms Related to Movements Dorsiflexion Plantarflexion Dr Eyad Mohamed Tolba Anatomical Terms Related to Movements Opposition Circumduction Dr Eyad Mohamed Tolba Anatomy of Skeletal System Dr Eyad Mohamed Tolba Bones * The skeletal system is formed of : Bones. Cartilages. Joints. Dr Eyad Mohamed Tolba Bones Def: Calcified connective tissue that forms most of the adult skeleton. Each bone is an organ that plays a role in the total functions of the skeletal system. Number: At birth, about 270 bones. In adults, approximately 206 bones. Osteology: - It is the science concerned with studying bones. Dr Eyad Mohamed Tolba Bones Functions of bones: o Provide a framework for the human body. o Provide leverage for movement. o Provide a store for calcium and phosphorus. o Provide a store for fat (yellow bone marrow). o Protect vital structures within the human body e.g. the skull for the brain. o Produce blood cells in the red bone marrow mainly in flat bones. Dr Eyad Mohamed Tolba Classifications of Bones Structure (2C) Ossification (2I) Position (2A) Shape Dr Eyad Mohamed Tolba Bones * According to structure: 1. Compact bones: - Characters: Dense, hard, ivory-like. Forms the protective external part of all bones. Example: Cortex of a long bone. Dr Eyad Mohamed Tolba Bones * According to structure:. 2. Cancellous bones: Characters: Porous, consists of bone trabeculae separated from each other by communicating spaces. Example: Epiphyses (ends) of long bones. Dr Eyad Mohamed Tolba Bones * According to ossification: 1. Intracartilagenous ossification: - A cartilaginous model is formed by chondrification of condensed mesenchymal (embryonic) tissue. - Then, bone is deposited in this model. - Examples, all bones of the limbs except the shaft of the clavicle. Dr Eyad Mohamed Tolba Bones * According to ossification: 2. Intramembranous ossification: - Bone is formed directly in a condensed mass of soft mesenchymal tissue (i.e. membrane-like). - Examples, the shaft of the clavicle, cap of the skull and bones of the face. Dr Eyad Mohamed Tolba Bones * According to position in the body: 1. Axial skeleton. 2. Appendicular skeleton. Dr Eyad Mohamed Tolba Axial Skeleton - It is the central framework of the human body (80 bones). - It includes the skull, vertebral column and thoracic cage. 1. The skull: - Forms the skeleton of the head region. - Made up of 22 bones (14 cranial and 8 facial) - Protects the brain, eyes and ears. Dr Eyad Mohamed Tolba Axial Skeleton 2. The vertebral column: - Forms the skeleton of the back. - Made up of 32-33 vertebrae, divided into: (a) Cervical (neck) region: 7 vertebrae. (b) Thoracic (chest) region: 12 vertebrae. (c) Lumbar (low back) region: 5 vertebrae. (d) Sacrum: 5 fused vertebrae. (e) Coccyx (tail): 3-4 fused vertebrae. - Protects the spinal cord. Dr Eyad Mohamed Tolba Axial Skeleton 2. The vertebral column: - It has two curvatures in the adult human spine: * Forward curves: - In cervical and lumbar region regions. * Backward curves: - In the thoracic and sacrococcygeal regions. Dr Eyad Mohamed Tolba Axial Skeleton 2. The Thoracic Cage: - It is the bony skeleton of the thorax. - It protects the heart and lungs. * Consists : (1) The sternum: anteriorly. (2) The ribs: 12 pairs laterally. (3) Thoracic vertebrae: 12 vertebrae posteriorly. Dr Eyad Mohamed Tolba Appendicular Skeleton - Forms the skeleton of the upper and lower limbs (126 bones). - Attached to the axial Skelton via the shoulder and pelvic girdles. * Upper limb: Shoulder girdle: clavicle & scapula Proximal segment: humerus. Middle segment: ulna medially & radius laterally. Distal segment: bones of the hand Carpus (8) Metacarpals (5) Phalanges 14 (3 for each finger, 2 for the thumb) Dr Eyad Mohamed Tolba The Skeleton Exoskeleton Vs Endoskeleton Dr Eyad Mohamed Tolba Appendicular Skeleton * Lower limb: Pelvic girdle: hip bone & sacrum. Proximal segment: Femur. Middle segment: tibia medially & fibula laterally. Distal segment: bones of the foot Tarsus (7) Metatarsals (5) Phalanges 14 (3 for each toe, 2 for the big toe) Dr Eyad Mohamed Tolba Bones * According to shape: 1. Long bones: - Have greater length than width as femur, tibia, humerus, radius…. 2. Short bones : - Cuboidal in shape and nearly equal in length, width, and depth as the carpals and tarsals. 3. Flat bones: - Thinner flattened bones as the scapula, ribs and the bones of the skull cap. 4. Irregular bones: - As the vertebrae and hip bone. Dr Eyad Mohamed Tolba * According to shape: Bones 5. Pneumatic bones: - Contain air-filled spaces as the skull bones (maxilla, frontal bones). 6. Sesamoid bones: - These are small bones, which develop inside the tendons of certain muscles and ligaments where there is considerable friction, compression, and physical stress. - Examples: Patella: in the tendon of quadriceps femoris muscle (largest sesamoid bone). Pisiform bone: in the tendon of flexor carpi ulnaris. Fabella: in the origin of the lateral head of gastrocnemius. Dr Eyad Mohamed Tolba Parts of Long Bone - A long bone consists of two ends and a shaft. - Each end is called epiphysis. - The shaft is known as diaphysis. - The epiphysis is composed of spongy (cancellous) bone and is covered by a layer of hyaline articular cartilage. - In a growing bone, the epiphysis is separated from the shaft by epiphyseal plate of cartilage. - This plate is the site of increase in length of the bone. - It ossifies at a certain age when the growth in length of the bone is completed. - The region of the shaft close of the cartilage plate is called metaphysis. Dr Eyad Mohamed Tolba Parts of Long Bone - The shaft is composed of a cylinder of compact bone enclosing a cavity called medullary cavity, which is filled with bone marrow. - The shaft is covered by a fibrous membrane called periosteum. - The periosteum is responsible for: 1. The increase in breadth of bones. 2. The repair of bone fracture. 3. It gives attachment to ligaments and tendons. Dr Eyad Mohamed Tolba Blood Supply of Long Bone * Supplied by blood vessels derived from 4 sources: Nutrient artery. Epiphyseal arteries. Metaphyseal arteries. Periosteal arteries. Dr Eyad Mohamed Tolba Anatomy of Integumentary system (Skin & Its appendages) Dr Eyad Mohamed Tolba Skin * Def: - The largest organ in the body which covers its entire external surface. Surface area: - Surface area 1.5-2 square meter. Layers: - The skin consists of 3 layers: 1. The epidermis. 2. Dermis. 3. Hypodermis. Dr Eyad Mohamed Tolba Skin * Layers: 1. The epidermis. Most superficial layer Formed of 4 to 5 layers of cells. Its superficial layer is formed of flat cells filled with keratin (Keratinized stratified squamous epithelium). keratin is a water-insoluble protein. It is devoid of blood vessels Its deepest layers contain specialized cells including melanocytes which synthesize melanin. This pigments protect the deeper layers of cells from the effects of ultraviolet light. Dr Eyad Mohamed Tolba Skin * Layers: 2. The dermis. Formed of connective tissue containing blood vessels, lymph vessels, sensory nerve endings, smooth muscles ,hair follicles, sweat & sebaceous glands. In its deep part the collagen bundles are arranged in parallel rows called :Lines of cleavage (Langer’s lines). 3. The hypodermis (subcutaneous fascia), Located beneath the dermis. This layer is the deepest skin layer and contains adipose lobules, sensory neurons, blood vessels, and scanty skin appendages, such as hair follicles. Dr Eyad Mohamed Tolba Skin * Cleavage lines of Langer: - The dermis contains collagen fibers arranged in parallel rows. - The direction of these rows is called Langer's lines. 1. Incisions made across Langer's lines: - Lead to more retraction, wound gapping and prominent scar formation. 2. Incisions made parallel to Langer's lines: - lead to less retraction, decrease wound gapping and less scar formation. The direction of Langer's lines: - Circumferential on the chest and abdomen. - Longitudinal along the extremities. Dr Eyad Mohamed Tolba Skin * Skin appendages: (4 appendages): - Nails. - Hairs. - Sebaceous glands. - Sweat glands. Dr Eyad Mohamed Tolba Dr Eyad Mohamed Tolba بسم اهلل الرمحن الرحيم َ ُ ْ ُ ْ َ َ َ َ ْ َ َ َ َّ َ َ َّ ْ َ َ ﴿ قالوا سبحانك ال ِعلم لنا ِإال ما علمتنا َّ َ َ َ ْ َ ُ ْ َ ُ ِإنك أنت العلِيم الحكِيم ﴾ صـدق الـلـه العـظـيم Dr Eyad Mohamed Tolba DR/ EYAD MOHAMED TOLBA Associate professor of Anatomy and Embryology Mansoura Faculty Of Medicine Year Two Lead Manchester Program, Taibah University Member of ESCPR Dr Eyad Mohamed Tolba Anatomy of Joints Dr Eyad Mohamed Tolba Joints Arthrology: It is the science of studying joints. Dr Eyad Mohamed Tolba Joints Def: Place of contact or articulation: o Between bones. o Between bones and cartilage. o Between bone and teeth. Functions: Hold bones together securely. Gives the rigid skeleton mobility. Dr Eyad Mohamed Tolba Joints Functional classification: Classified according to the degree of movement allowed into : 1. Joint types restricted mainly to the axial skeleton where firm attachments and protection of internal organs are priorities include: o Synarthroses: – Immovable joints o Amphiarthroses: – Slightly moveable joints 2. Joints predominate in the limbs where mobility is important: o Diarthroses: – Freely moveable joints. Dr Eyad Mohamed Tolba Joints Structural classification: Classified according to the nature of the tissue between the articulating bones into 3 types: fibrous Cartilaginous Synovial Dr Eyad Mohamed Tolba Fibrous joints Characters: - The articulating bones are separated from each other by fibrous tissue. - No or very limited movement. Types: S. G. S 1. Sutures. 2. Gomphosis (dentoalveolar joint). 3. Syndesmosis. Dr Eyad Mohamed Tolba Fibrous joints 1. Sutures: - Between the bones of the skull. - The bones of the skull are separated from each others of a thin layer of dense irregular fibrous connective tissue. - No movement. Dr Eyad Mohamed Tolba Fibrous joints 2. Gomphosis (dentoalveolar joint): - The only example is the articulation between the root of the teeth and their sockets. - The root of the tooth (cone- shaped peg) is fixed to its bony socket by a dense irregular fibrous connective tissue (periodontal ligament). - A healthy gomphosis permits no movement. Dr Eyad Mohamed Tolba Fibrous joints 3. Syndesmosis: - Between the lower ends of tibia and fibula (inferior tibio-fibular joint). - The two bones are connected by excessive amount of dense irregular?? fibrous tissue typically arranged as a bundle (ligament). Dr Eyad Mohamed Tolba Cartilaginous joints Characters: * The articulating bones are separated from each other by cartilage. * Slightly mobile. Types: 1. Primary (synchondroses) 2. Secondary (symphysis) Dr Eyad Mohamed Tolba Cartilaginous joints 1. Primary (synchondroses) (synarthrotic): - The intervening cartilage is hyaline - Ultimately ossified by age. - Example: - The joints between epiphysis and diaphysis of growing long bones. - 1st sternocostal joint - Costochondral joints Dr Eyad Mohamed Tolba Cartilaginous joints 1. Secondary (Amphiarthrotic): - The intervening cartilage is fibrocartilage. - The articular surfaces of the bones are covered with a thin layer of hyaline cartilage. - Slightly moveable. - Example: joints in the median plane of the body. Intervertebral discs. Symphysis pubis. Dr Eyad Mohamed Tolba Synovial joints Characters: ◘ Freely mobile (diarthrotic). ◘ The articular surfaces are covered by a thin layer of hyaline cartilage ◘ The articular surfaces are separated by a joint cavity. ◘ The fibrous capsule: - Completely surrounds the joint. Dr Eyad Mohamed Tolba Synovial joints Characters: ◘ The synovial membrane: - Lines the inner surface of the capsule and covers the non-articular surfaces of the bones. - Responsible for production and absorption of the synovial fluid. ◘ The synovial fluid: Fills the joint cavity. Lubricates the articular surfaces. Allows free movement of the joints. Dr Eyad Mohamed Tolba Synovial joints Characters: ◘ The intraarticular structures: -These are structures inside the joint such as: 1.Cartilaginous structures which may be in the form of: ▪ A disc as in the temporomandibular joint. ▪ A labrum as in shoulder joint. ▪ A meniscus as in the knee joint. 2. Ligaments: - The cruciate ligaments inside the knee joint. Dr Eyad Mohamed Tolba Synovial joints Characters: ◘ The intraarticular structures: 3.Tendon of a muscle: As: - Tendon of the long head of biceps in shoulder joint. - Tendon of popliteus in knee joint. Dr Eyad Mohamed Tolba Synovial joints * Classified according to the number of axes around which movements take place and shape of articulating surface into: 1. Uniaxial: - The movements occur around a single axis. 1. Biaxial: - The movements occur around two axes. 1. Polyaxial: -The movements occur around many axes. Dr Eyad Mohamed Tolba Uniaxial Synovial joints - They are subdivided into: a. Hinge joints: - The movements occur around a transverse axis. - Flexion and extension are permitted. - Example:. Elbow joint. Dr Eyad Mohamed Tolba Uniaxial Synovial joints b. Pivot joints: - Movements occur around a longitudinal axis. - Rotation movements are permitted. - Example:. The superior radio-ulnar joint.. Median atlanto-axial joint. Dr Eyad Mohamed Tolba Biaxial Synovial joints - They are subdivided into: a. Ellipsoid joints: - An oval-shaped convexity of one bone fits into an oval-shaped concavity of another bone. - Example: - Wrist joint. Dr Eyad Mohamed Tolba Biaxial Synovial joints b. Saddle joint: -The articular surfaces are reciprocally concavo-convex and resemble a saddle on a horse’s back. - Example: - Carpometacarpal joint of the thumb. Dr Eyad Mohamed Tolba Polyaxial Synovial joints - They are subdivided into: a. Ball-and-socket joints: - A rounded head is received into a cup-shaped concavity. - Example: Hip joint. Shoulder joint. Dr Eyad Mohamed Tolba Polyaxial Synovial joints b. Plane joint (Gliding): ???? - The articulating surfaces are flat. - Movements permitted are only sliding. - Example: Intertarsal joints. Intercarpal joints. Dr Eyad Mohamed Tolba Dr Eyad Mohamed Tolba Joints Nerve supply of joints (articular nerves): - Joints are innervated by the same nerves which supply the muscles acting on these joints. - The capsule and the ligaments receive abundant sensory nerve supply Dr Eyad Mohamed Tolba Joints Hilton's law: - The nerve supplying a joint also supplies the muscles moving that joint and the skin overlying the insertion of these muscles. Dr Eyad Mohamed Tolba * Stability of Joint: Joints - Depends upon: Shape of the articulating bones. Contraction of the surrounding muscles. Position and strength of the accessory ligaments. Dr Eyad Mohamed Tolba Dr Eyad Mohamed Tolba Dr Eyad Mohamed Tolba بسم اهلل الرمحن الرحيم َ ُ ْ ُ ْ َ َ َ َ ْ َ َ َ َّ َ َ َّ ْ َ َ ﴿ قالوا سبحانك ال ِعلم لنا ِإال ما علمتنا َّ َ َ َ ْ َ ُ ْ َ ُ ِإنك أنت العلِيم الحكِيم ﴾ صـدق الـلـه العـظـيم Dr Eyad Mohamed Tolba DR/ EYAD MOHAMED TOLBA Associate professor of Anatomy and Embryology Mansoura Faculty Of Medicine Year Two Lead Manchester Program, Taibah University Member of ESCPR Dr Eyad Mohamed Tolba Anatomy of Muscles Dr Eyad Mohamed Tolba Muscles Myology: It is the science concerned with studying muscles. Dr Eyad Mohamed Tolba Muscles * Functions: 1. Body Movement: - As in walking, running, writing, chewing, and swallowing. Dr Eyad Mohamed Tolba Muscles * Functions: 2. Heat production: - Considered as the primary source of body heat. - Heat production occurred during muscle contraction is used to maintain normal body temperature. Dr Eyad Mohamed Tolba Muscles * Functions: 3. Body support and maintenance of posture: - The skeletal muscles maintain posture, stabilize joints and support viscera. 4. Regulation of body fluids movements: - Smooth muscles regulate the movement of organs, lymphatic and blood. 5. Protection of viscera: - The abdominal muscles protect the abdominal organs. Dr Eyad Mohamed Tolba Muscles * Basic properties of muscle tissue: 1. Electrical excitability (Irritability): - It is the ability to respond to certain stimuli by producing electrical signals. 2. Contractility: - It is the ability of muscular tissue to contract (shorten) when stimulated. 3. Extensibility: - It is the ability of muscular tissue to stretch, within limits, without being damaged. 4. Elasticity: - It is the ability of muscular tissue to return to its original length and shape after contraction or extension. Dr Eyad Mohamed Tolba Muscles Classification : Classified into 3 types: Smooth, Cardiac and Skeletal. Smooth Cardiac Skeletal Dr Eyad Mohamed Tolba 2. Characters: Smooth Muscle. Site: - Wall of internal viscera. - Wall of airways. - Wall of blood vessels.. Contraction: - Involuntary.. Striation: - Absent.. Nerve supply : - Autonomic.. Muscle cell: - Long Spindle-shaped with single nucleus (uninucleated). - Closely arranged in bundles or sheets. Dr Eyad Mohamed Tolba Cardiac Muscle 2. Characters:. Site: - In myocardium (heart).. Contraction: - Involuntary.. Striation: - Present.. Nerve supply : - Autonomic.. Muscle cell: - Long cylindrical with single nucleus (uninucleated). - Branch and fuse together to form the myocardium of the heart. - Arranged in whorls and spirals. Dr Eyad Mohamed Tolba Skeletal Muscle 2. Characters:. Site: - Attached to the skeleton.. Contraction: - Voluntary.. Striation: - Present.. Nerve supply : - Somatic.. Muscle cell: - Multinucleated. Dr Eyad Mohamed Tolba Types of Muscles Smooth Cardiac Skeletal Site Wall of internal viscera In the myocardium Attached to the skeleton, hence its and blood vessels of the heart name Contraction Involuntary Involuntary Voluntary Striation Absent Present Present Nerve supply Autonomic Autonomic Somatic Spindle-shaped with Branch and fuse together; with Multinucleated Muscle cell single nucleus single nucleus (one syncytium) \s \s \s Dr Eyad Mohamed Tolba Dr Eyad Mohamed Tolba Skeletal Muscles Def: - Muscles which are attached to the skeleton and hence its name. - There are more than 600 muscles in the human body. - Most of these muscles are attached to the bones of the skeleton by tendons, although a few muscles are attached to the undersurface of the skin. -Collectively, the skeletal muscles account for approximately 40% of the body weight. Dr Eyad Mohamed Tolba Skeletal Muscles Parts of skeletal muscles: * Red fleshy contractile part called belly or head. * White fibrous non-contractile part: it may be rounded or ribbon-like (Tendon) or flat sheet (Aponeurosis). Dr Eyad Mohamed Tolba Skeletal Muscles Attachments of skeletal muscles: - A muscle has 2 attachments: * Origin: is the more fixed attachment. * Insertion: is the more mobile attachment. * When a muscles contract, its fibers shorten and the insertion moves towards the origin, thus producing movement at the related joint. Dr Eyad Mohamed Tolba Skeletal Muscles * Attachments of skeletal muscles: - The insertion is usually by: Rounded tendon. Aponeurosis (flat fibrous sheet). Median raphe. Dr Eyad Mohamed Tolba Skeletal Muscles Criteria Used to Name Muscles: 1. Shape: - Relative shape of the muscle. - Deltoid: Triangular. - Trapezius: Trapezoid. 2. Size: - Relative size of the muscle. - Maximus Largest, Minimus Smallest, Longus Long, Brevis Short 3. Site (location): - Temporalis: in the temporal region. - Pectoralis muscles: in the pectoral region. Dr Eyad Mohamed Tolba Skeletal Muscles Criteria Used to Name Muscles: 4. Direction: * Orientation of muscle fibers relative to the body’s midline. - Rectus: Parallel to midline. - Transverse: Perpendicular to midline. - Oblique: Diagonal to midline. 5. Relative position: - Lateral, medial, internal and external 6. Action: Principal action of the muscle. - Flexor, Extensor, Abductor, Adductor, Levator, Depressor etc. Dr Eyad Mohamed Tolba Skeletal Muscles Criteria Used to Name Muscles: 7. Number of origins: number of tendons of origin. - Biceps two heads. - Triceps three heads. - Quadriceps four heads. 8. Attachment (origin and insertion): - Sternocleidomastoid; originating on the sternum and clavicle and Inserting on mastoid process. Dr Eyad Mohamed Tolba Skeletal Muscles Classified according to the following (FAN) : * Form (internal structure). * Action. * Number of joint they act on. Dr Eyad Mohamed Tolba Skeletal Muscles Classification according to form: 1. Muscles with fibers arranged parallel with the line of pull. a. Quadrilateral: e.g. thyrohyoid. b. Strap-like: e.g. sartorius. c. Strap-like with tendinous intersections: e.g. rectus abdominis. d. Fusiform: e.g. lumbrical. e. Rhomboid. Dr Eyad Mohamed Tolba Dr Eyad Mohamed Tolba Skeletal Muscles Classification according to form: 2. Muscles with pennate fibers (pennate = feather like) arranged obliquely to the line of pull: a. Unipennate: - The fibers lie on one side of the tendon, e.g. flexor pollicis longus. b. Bipennate: - The fibers lay on both sides of the tendon, e.g. rectus femoris. Dr Eyad Mohamed Tolba Skeletal Muscles Classification according to form: 2. Muscles with pennate fibers arranged obliquely to the line of pull: d. Multipennate: - The muscle contains numerous bipennate unites, which converge on the tendon of the muscle, e.g. deltoid. c. Circumpennate: - The fleshy fibers converge on the tendon, which is placed centrally in the axis of the muscle, e.g. tibialis anterior. Dr Eyad Mohamed Tolba Skeletal Muscles Classification according to form: 3. Muscles with fibers arranged obliquely to the line of pull but are (not pennate): ▪ Triangular: fibers the muscle fibers converge into a narrow terminal tendon e.g. temporalis. ▪ Spiral: e.g. supinator. ▪ Cruciate (X-shaped): e.g. masseter ▪ Circular: the muscle fibers are arranged in concentric rings, e.g. orbicularis oculi. Dr Eyad Mohamed Tolba Skeletal Muscles Classification according to form: 4. Muscles which may have more than one fleshy head: * Biceps muscle: 2 heads. * Triceps muscle: 3 heads. * Quadriceps muscle: 4 heads. * A muscle may have 2 bellies attached together by an intermediate tendon, e.g. digastric. Dr Eyad Mohamed Tolba Skeletal Muscles Classification according to action: 1. Prime movers: - Muscles that initiate a particular movement. 2. Antagonist: - These are muscles, which oppose the action of prime movers. 3. Synergists: - Act to steady and to eliminate unwanted movements in proximal (intermediate) joints while distal joints are in action. 4. Fixator (stabilizers): These muscles help the prime mover by fixing its origin or stabilizing the joint upon which the prime mover acts. 5. Action of paradox: - Muscles acting against the force of gravity. Dr Eyad Mohamed Tolba Dr Eyad Mohamed Tolba Skeletal Muscles III. According to the number of joints they act upon: o Uni-articular: - Act on only one joint. o Bi-articular: - Act on two joints. o Multi-articular: - Act on more than two joints. Dr Eyad Mohamed Tolba Dr Eyad Mohamed Tolba BODY FLUIDS and HOMEOSTASIS BY Prof.Dr. Ahmed ElGendy Medical Physiology Mansoura and Taibah Faculty of Medicine Prof Dr Ahmed Elgendy OBJECTIVES To: 1 Define the concepts: intracellular fluid (ICF), extracellular fluid (ECF), interstitial fluid (ISF), and total body water. 2Discuss the distribution of total body H2O (TWB) in the body. 3- List the ionic composition of different body compartments 4- Explain the influence of age, sex and weight on the size of the total body water and its phases. 5- Identify what is meant by homeostasis, control and feedback mechanisms Prof Dr Ahmed Elgendy Body Fluids -The human body is made up of different systems e.g. digestive system. -Each system consists of many organs that made up of many tissues of complementary functions. -Each tissue consists of millions of similar cells. -The cell is the basic unit of structure and function in the body. -The cells of the human body are eukaryotic (have true nucleus) not prokaryotic. Prof Dr Ahmed Elgendy Systems Cells Tissues Organs Prof Dr Ahmed Elgendy Body Fluids -Eukaryotes are surrounded by cell membrane that allow for selective communication between intracelluar and extracellular fluid. -cells contain many organelles that perform specific functions. Prof Dr Ahmed Elgendy Prof Dr Ahmed Elgendy Body composition In average young adult male: Body composition % of body weight Protein, & related substances 18% Fat 15% Mineral 7% Water 60% Prof.Dr.Ahmed ElGendy Prof Dr Ahmed Elgendy Body Fluids -The body fluids are solutions of water, dissolved in this water many organic molecules (carbon- containing molecules such as carbohydrates, lipids, proteins, and nucleic acids), as well as inorganic molecules and ions. Value: -The total body fluids constitute about 65% i.e. 40 liters in an adult weighing 70 Kg. Prof Dr Ahmed Elgendy Compartments of body fluids Intracellular fluid Extracellular fluid -2/3 of body fluid -1/3 of body fluid -25 liters -15 liters i-Plasma (3 liters). ii-Interstitial fluid (12 L) Iii-Transcellular fluid (1 liter). Digestive juices, Prof Dr Ahmed Elgendy cerebrospinal fluid Fluid compartments Intracellular Extracellular fluid fluid (ICF) (ECF) Is the fluid within the Is the fluid found outside cells, known as cytosol the cells (40% of TBW) (20% of TBW) Plasma water Interstitial fluid (5% of TBW) (15% of TBW) Is the fluid component of Is the fluid surrounding blood the cells Prof Dr Ahmed Prof.Dr.Ahmed Elgendy ElGendy Intracellular compartment Prof Dr Ahmed Elgendy Prof.Dr.Ahmed ElGendy Prof Dr Ahmed Elgendy Distribution of body fluids ECF Plasma Interstitial f. ICF Prof Dr Ahmed Elgendy H20 constitutes about 60 % of body weight i.e. about 42 L in 70 Kg man. ICF ECF 1. It constitutes 40 % body weight 1. It constitutes 20 % body weight ( about 28 L in 70 Kg man) ( about 14 L in 70 Kg man) − It is subdivided into: a. Plasma: 5% (3.5 L) b. Interstitial Fluid:15 %(10.5 L) 2. Chief cation: K+ ( 140 mEq/L). Na+ ( 145 mEq/L). 3. Chief anion: Proteinates ( 40 mEq/L). Cl- ( 103 mEq/L) Phosphates ( 75 mEq/L). Prof Dr Ahmed Elgendy(28 mEq/L) HCO3- Prof.Dr.Ahmed ElGendy Composition of body fluids Na+ K+ Cl- Pt- Inside 14 140 4 16 Nerve cell 10 time 35 25 time 8 Outside 140 4 100 2 m.eq/liter m.eq/liter m.eq/liter gm/dl Prof Dr Ahmed Elgendy Prof Dr Ahmed Elgendy Prof.Dr.Ahmed ElGendy r1 PERCENTAGE OF H2O IN TISSUES Prof.Dr.Ahmed ElGendy Prof Dr Ahmed Elgendy Prof Dr Ahmed Elgendy -The volume of the compartment is calculated as follow: Amount of dye Volume of fluid compartment = Concentration of dye Dye dilution principle Prof Dr Ahmed Elgendy كمية المياه الالزمة يوميا للجسم كمية عدد اللترات= الوزن × ÷ ٣٠ ١٠٠٠لتر عدد االكواب =الوزن ×٢٥٠ ÷ ٣٠ كوب Prof Dr Ahmed Elgendy Water Balance -total body water (TBW) constitutes about: - 60% of the total body weight in adult men - 50% in women - 70% in children - decreased In old age Body water is kept constant by adjusting water input and water output. Prof Dr Ahmed Elgendy Percentage of body water Prof Dr Ahmed Elgendy Water balance Water input or intake Water output or loss = 2400 ml/day = 2400 ml/day. a) Exogenous water: a)Insensible water Ingested about 2200 loss from skin: 700 ml. ml/day. b)Sweating:100 ml. b) Endogenous water: - as a result of metabolism = c- Feces: 100 ml. about 200 ml/day. d- Urine:1500 ml. Prof Dr Ahmed Elgendy Functions of body water Prof Dr Ahmed Elgendy Functions of body water 1-It is required for all chemical reactions inside the body. 2-It acts as powerful solvent that dissolve various substances. 3-It is important in regulation of body temperature through sweating. 4-It moistens tissues such as mouth, eyes and nose. Prof Dr Ahmed Elgendy Functions of body water 5-Helps digestion. 6-Helps absorption. 7-Filteration at the level of the capillaries. 8-Excretion in gastrointestinal tract (GIT) and kidney. 9-Refractive medium in the eye. Prof Dr Ahmed Elgendy Control of Water Balance Control of Water input Control of Water input -Controlled by thirst center Controlled mainly by in anterior hypothalamus. adjusting the urine volume -Thirst is stimulated by: (in the kidney) by 1- ed osmolarity antidiuretic hormone (hypertonicity) (ADH) which is secreted by 2- ed blood volume posterior pituitary gland. (hypovolaemia) 3-angiotensin II Prof Dr Ahmed Elgendy Definitions Homeostasis – state of balance in the body. Stimulus- a change in the environment (thermal, mechanical ……….. etc.) Feedback mechanisms/loops – processes by which the body maintains levels. Usually uses nervous and hormonal control systems to conduct processes. Prof Dr Ahmed Elgendy Homeostasis: Dynamic Constancy Homeostasis Maintenance of a constant internal environment (ECF) for best condition of cells as regards to:- Body Temperature - Blood pressure - Blood pH - O2 and CO2 concentration - Osmoregulation - Water balance - Blood glucose Steady state Balance between demands Prof placed on body and the physiological Dr Ahmed Elgendy response to those demands. Homeo-stasis = same state Def: they are the mechanisms that keep the internal environment constant. -This keeps the normal cellular functions as: - Body water. - Ions - body temperature. - blood glucose - PH. - arterial blood press. -There is a narrow range of change ;more than this range the cell function is greatly affected. Prof Dr Ahmed Elgendy Most body systems try to keep homeostasis ◆ It is maintained by: ◆ Cardiovascular system ◆ Lungs ◆ Kidneys ◆ GI tract ✦Skin These body systems in turn are controlled by two control systems: NERVOUS and HORMONAL Prof Dr Ahmed Elgendy Components of a Biological Control Systems Afferent Efferent Prof Dr Ahmed Elgendy Homeostatic functions are regulated by: a- Nervous system (rapid). b- Endocrine system (slow). Prof Dr Ahmed Elgendy Feedback mechanisms these are the mechanisms that keep the system constant. 1-Negative feedback mechanisms (most common): -these mechanisms keep the system constant and the response inhibits the stimulus. 2-Positive feedback mechanisms: -the response es the stimulus. Prof Dr Ahmed Elgendy Negative Feedback Fig 1.1 Prof Dr Ahmed Elgendy NEGATIVE FEEDBACK POSITIVE FEEDBACK Prof Dr Ahmed Elgendy 1-Negative feedback mechanisms (most common) these mechanisms keep the system constant and the response inhibits the stimulus, e.g. a) ed blood CO2 → hyperventilation → washout of excess CO2 →ed CO2 in blood to normal level. b)ed blood glucose→ed insulin secretion → ed glucose utilization→ed glucose level to normal. Prof Dr Ahmed Elgendy Negative feed back CO2 Hyperventillation CO2 wash Prof Dr Ahmed Elgendy Negative feed back Glucose Insulin Glucose utilization Prof Dr Ahmed Elgendy Prof Dr Ahmed Elgendy 2- Positive feedback mechanisms Heart failure → ed cardiac output → ed ABP → ed coronary blood flow → Heart failure. Prof Dr Ahmed Elgendy Positive feed back Heart failure ↓ cardiac output ↓ blood pressure Prof Dr Ahmed Elgendy Positive feedback cycles are useful Cervical dilatation (during labour) increases uterine contractions descent of baby more cervical dilatation more uterine contractions more descent of baby, till complete labor Prof Dr Ahmed Elgendy Prof Dr Ahmed Elgendy Death cycle (Death due to vicious circle) Heart failure (weakness of heart) ↓ Coronary ↓ Cardiac blood flow output ↓ Arterial blood pressure Prof Dr Ahmed Elgendy References - Guton and Hall text book of medical physiology 12th edition 2014. -Ganong Text book of medical physiology 10th edition 2010. Prof Dr Ahmed Elgendy [email protected] Prof Dr Ahmed Elgendy Physiology of Autonomic Chemical Transmitters Prof.Ahmed El-Gendy Mansoura and Taibah Faculty of Medicine Prof Ahmed ElGendy Learning outcomes A 21.Understand the theory of chemical M transmission. o d 2.Describe acetylcholine storage, release, and ul e 1- l e fate. L ev 3.Identify the types of acetylcholine receptors. S4.List the actions of acetylcholine. e m et Prof Ahmed ElGendy Reference: sr 1- NEUROTRANSMITTERS OF ANS Prof Ahmed ElGendy A 2 M o Prof Ahmed ElGendy d ul e 1- l e Lev Semetsr1- A 2 o 1 M d ul e - L l e ev S e m et sr 1- Prof Ahmed ElGendy Reference: Reference: Semetsr1- Level 1- Module 2 A Prof Ahmed ElGendy Prof Ahmed ElGendy Prof. Ahmed El-Gendy Chemical Transmitters Sympathetic Parasympathetic Preganglionic fibers secretes Preganglionic secrete acetylcholine (the chemical acetylcholine (cholinergic transmitter at autonomic fibers). ganglion), thus they are Postganglionic fibers cholinergic fibers. secrete acetylcholine in all Postganglionic secrete nor- sites (cholinergic). adrenaline in all sites except postganglionic to:- sweat glands skeletal ms. blood vessels where they secrete Prof Ahmed ElGendy acetylcholine (cholinergic ) Chemical transmitters & Receptors Cholinergic muscarinic at sweat glands & Sk. Ms blood vessels Prof. Ahmed El-Gendy NEUROTRANSMITTERS OF ANS Prof Ahmed ElGendy Cholinergic transmission A 2 M o d ul e 1- l e Lev Semetsr1- Prof Ahmed ElGendy 2) Biosynthesis of Acetylcholine Reference: Prof Ahmed ElGendy A 2 M o d ul e 1- l e L ev S e m et Reference: sr Prof Ahmed ElGendy 1- ProfProf. Ahmed ElGendy Ahmed El-Gendy Prof Ahmed ElGendy Prof. Ahmed El-Gendy Reference: Semetsr1- Level 1- Module 2 A Prof Ahmed ElGendy Prof Ahmed ElGendy Contents Acetylcholine receptors Identify the types of acetylcholine receptors. Reference: Prof Ahmed ElGendy A 2 M o d ul Prof Ahmed ElGendy e 1- l e Lev Semetsr1- Myasthenia gravis Definition: A rare --utoimmune diseas that affect neuro- uscular iunction ( '" characterized oy marked muse] weaKness a rapid onset of fatig with moderate uscular exercise. Prof Ahmed ElGendy A 2 odule 1 M - l e ev L emetsr1- S Prof Ahmed ElGendy Reference: A 2 o 1 M d ul e L - l e ev S e m et sr 1- Reference: Prof Ahmed ElGendy Adrenergic transmission * Noradrenaline is the chemical transmitter of sympathetic nervous system. * Noradrenaline is a member of catecholamines. * Catecholamines include: Noradrenaline, adrenaline and dopamine. Prof Ahmed ElGendy ProfProf. Ahmed ElGendy Ahmed El-Gendy SITE OF RELEASE 1 All symp postganglionic nerve fibers except those supplying skeletal muscles blood vessels, sweat glands & skin. 2 Some CNS synapses. 3 Supra renal medulla (SRM): adrenaline (80%) and noradrenaline (20%). Prof Ahmed ElGendy Norepinephrine & Epinephrine B. Synthesis & Fate of Norepinephrine & Epinephrine: 1. Norepinephrine: - Is the 1ry NT released from postganglionic sympathetic neurons. - Is synthesized in the nerve terminals & released into the synapse to bind to its receptor on the postsynaptic membrane. - Is removed from the synapse by: 1. Active reuptake (50-80%) for reuse or 2. Enzymatic inactivation: by monoamine oxidase (MAO) in presynaptic axon terminals & catechol-O-methyltransferase (COMT) in postsynaptic membrane. 2. Epinephrine: - Is synthesized from NE. - Is secreted along with NE from adrenal medulla. Prof Ahmed ElGendy Prof. Ahmed El-Gendy Prof Ahmed ElGendy Reference: https://www.cvpharmacology.com/norepinephrine STORAGE - Mainly ➔ vesicles in nerve terminal (one thousand molecule or more). - Some ➔ free in cytoplasm - In SRM, adrenaline and NA are stored in chromaffin cells. Reference: Prof Ahmed ElGendy RELEASE - when the action potential reaches the axon terminal ➔ increase permeability to Ca2+ ➔ Ca2+ influx ➔ vesicles fuse with the membrane ➔ vesicles rupture ➔ emptying their content outside nerve fiber (exocytosis) ➔ chemical transmitter cross the cleft (10-30 nm) & bind to its receptors on effector organ. Reference: Prof Ahmed ElGendy Semetsr1- Level 1- Module 2 A - Stimulation of symp. preganglionic nerve fibers relaying on chromaffin cells in SRM ➔ release of adrenaline and NA. Reference: Prof Ahmed ElGendy MECHANISM OF ACTION OF NORADRENALINE Semetsr1- Level 1- Module 2 A - When the chemical transmitter binds with its receptors on postsynaptic membrane ➔ change of cell membrane permeability to various ions ➔ * permeability to Na+ & Ca2+ ➔ Na+ & Ca2+ influx ➔ depolarization (stimulation). * permeability to K+ & Cl- ➔ K+ efflux or Cl- influx ➔ hyperpolarization (inhibition). Reference: Semetsr1- Level 1- Module 2 A - Noradrenaline bind with its receptors ➔ stimulation of adenyl cyclase ➔ conversion of ATP into cAMP ➔ initiate intracellular activities. Reference: Prof Ahmed ElGendy Prof Ahmed ElGendy REMOVAL Semetsr1- Level 1- Module 2 A (1) Neuronal uptake: - Account for removal of 85% of secreted noradrenaline. - Noradrenaline is actively reuptaken into the adrenergic nerve ending where it is stored in the vesicles or oxidized by mono amine oxidase (MAO) enzyme. Reference: Prof Ahmed ElGendy Prof Ahmed ElGendy Semetsr1- Level 1- Module 2 A (2) Extra neuronal uptake (15%): NA is inactivated by catechol-O- methyl transferase (COMT) enzyme. - Account for removal of 15% of secreted noradrenaline. - Noradrenaline is inactivated by catechol-o-methyl transferase (COMT) enzyme (which is present in all tissues). (3) Excretion in urine: (conjugated with glucuronic acid). Reference: Prof Ahmed ElGendy MAO COMT Monoamine oxidase Catechol-O-methyl transferase Neuronal Extra neuronal Produce oxidation Produce methylation Account for removal of 85% of Account for removal of 15% of noradrenaline noradrenaline Present in the mitochondria of Present in all tissues diffusely adrenergic nerve fiber and other especially kidney and brain tissues as liver and kidney Reference: Prof Ahmed ElGendy Prof Ahmed ElGendy 1- Def. Are the receptors which respond to catecholamines adrenaline and noradrenaline NE Adrenergic receptors Physiological Actions Cell Reference: Prof Ahmed ElGendy 2-Types: Alpha 1 (excitatory ) Alpha Alpha 2 Adrenergic (inhibitory ) receptors Beta Beta 1,2,3,4,5 Reference: Prof Ahmed ElGendy Reference: Prof Ahmed ElGendy Prof Ahmed ElGendy Postsynaptic Adrenergic Receptors -Receptors -Receptors Main NT NE E ≥ NE Action 1: mostly excitatory 1: mostly excitatory according - VC in skin & GIT - Heart rate, conduction o type of - Contraction of: velocity & contractility of receptors * dilator pupillae ms. heart not * GIT sphincters - Lipolysis → FFA Prof Ahmed ElGendy chemical - Glycogenolysis transmitter - ↑ Endocrine secretions 2: mostly inhibitory s - Relaxation of GIT ms. 2: mostly inhibitory - VD of coronary - VD in skeletal ms. - Relaxation of ms. of: * bronchi * GIT * urinary bladder Mechanism 1 → I.C. Ca2+ → cAMP of Action 2 → cAMP Prof. Ahmed El-Gendy References 1. https://inside.ucumberlands.edu/acade mics/biology/faculty/kuss/courses/ Nervous%20system/Sympathetic Parasympathetic.htm 2. https://www.memorangapp.com/flashca rds/84263/ 1-4+Autonomic+ NS+ Overview/ 3. http://humanphysiology.academy/Neurosciences%202015/Chapter%202/P.2.4%20Autonomic %20NS.html 4. https://cvpharmacology.com/autonomi c_ganglia 5. John E. Hall. (2016): Guyton and Hall, Textbook of medical physiology. 13th edition. 6. Barrett K.E., Barman S.M., Boitano S., and Brooks H.L. (2016): Ganong’s review of medical Prof Ahmed ElGendy Prof.Dr. Ahmed ElGendy Medical Physiology Mansoura and Taibah Faculty of Medicine Prof Ahmed ElGendy Medical Physiology BY Faculty of Medicine Prof.DR.Ahmed Elgendy Taibah University Objectives Passive transport (diffusion): Definition Factors affecting Types Simple diffusion Facilitated diffusion Active transport Definition Prof Ahmed ElGendy Types primary active transport Secondary active transport Endocytosis Definition Types Pincytosis Phagocytosis Exocytosis. *All animal cells are surrounded by a cell membrane = Semipermeable *Thickness =Very thin = 7.5 nm = 75 A *Elastic *Dynamic Prof Ahmed ElGendy Prof Ahmed ElGendy. It is a fluid lipid bilayer with floating protein & CHO 1-Lipids: 42% -Phospholipids = 25% (responsible for flexibility of CM) -Cholesterol (responsible for toughness of CM) -Glycolipids Prof Ahmed ElGendy 2-Proteins: 55% ( Active part ) -Integral or intrinsic proteins -Peripheral or extrinsic proteins - The more The cell is active The more protein content 3-CHO: 3% Prof Ahmed ElGendy Prof Ahmed ElGendy Prof Ahmed ElGendy Prof Ahmed ElGendy Prof Ahmed ElGendy. 1- Passive Transport ( No Energy ): - Diffusion - Osmosis 2- Active Transport ( Need Energy ): - Primary & Secondary - Vesicular transport Prof Ahmed ElGendy Prof Ahmed ElGendy I- Simple Diffusion It is a passive process i.e. it does not need energy. Definition:- It is the transport of 'solute' or a 'gas' across a semi permeable membrane from region of high concentration (C) or pressure to a lower one. So, it is a downhill process. Prof Ahmed ElGendy Simple Diffusion Prof Ahmed ElGendy Diffusion of substances across the cell membrane: (1) "Lipid soluble substances": g.(O2) & (CO2) - glycerol & urea diffuse through: a. Lipid bilayer b. Pores or channels So, they have "high" rate of diffusion. (2) "H2O soluble substances": e.g. ions (Na+ & K+ ) diffuse through channels only, So, they have "low" rate of diffusion. Prof Ahmed ElGendy Some of these channels are continuously opened non gated "leak channels " while others can open and close "gated channels". These gated channels open due to: a. Change in the electrical membrane potential i.e. "voltage gating" e.g. Na+ & K+ channels. b. Binding of a neurotransmitter (e.g. acetyl choline) “ligand gating" e.g. acetylcholine–gated ion channel at neuromuscular junction Prof Ahmed ElGendy Types of channels in the cell membrane:- A-Leak channels (non gated channels):- Has no gate (continuously opened) i.e. through which ions continuously leak e.g., Na+-K+ leak channels. It is 50 times more permeable to K+ than Na+ B-Gated channels:- Have gates (open and close) and are of 2 types: 1-Voltage-gated channels: Their gates open as a result of change in the electric potential (voltage) across the cell membrane, e.g., voltage gated Na+ channel, K+ channel and Ca2+ channel. 2-Ligand-gated (chemical-gated) channels: Their gates open as a result of binding (ligation) of a chemical substance with receptor on the channel protein, e.g., acetylcholine–gated ion channel at motor end plate (neuromuscular junction) Prof Ahmed ElGendy Prof Ahmed ElGendy Prof Ahmed ElGendy Types of channels in cell membrane Non gated (leak) channels Gated channels Voltage gated channels Ligand gated channels + + Stimulus - - - - + + Ligation of AC AC Prof Ahmed ElGendy Prof Ahmed ElGendy Prof Ahmed ElGendy Factors Affecting Diffusion Diffusion is directly proportional with: 1Lipid solubility (S) 2Concentration or pressure gradient (C1- C2). 3-Surface area (A) 4-Temperature (T). Diffusion is inversely proportional with: 1- Thickness of the membrane (t) 2- Molecular weight (MW) (MW) STA (C1 − C2 ) Therefore D t MW Prof Ahmed ElGendy II. Facilitated Diffusion It is also a passive process. It needs a carrier protein to transport "large" & "lipid insoluble " molecules e.g. glucose and most amino acids. Mechanism:- Each molecule units with a receptor in the carrier protein. This will lead to a configuration change (change in shape) in the carrier allowing the passage of such large molecule to the inside. Prof Ahmed ElGendy Types:- -If the carrier transports only one molecule, it is called uniport. -If the carrier transports two molecules in the same direction, it is called symport (Co- transport). -If the carrier transports two molecules in opposite directions (exchangers), it is called antiport. (Counter- transport). Prof Ahmed ElGendy Characters of facilitated diffusion 1-It needs a carrier protein. 2 Specificity:- Each carrier is specific for one or few substances. 3 Competitive inhibition:- Similar molecules compete with each other for the "same" carrier, so, they inhibit, the transport of each other. 4 Saturation:- As the concentration of the substance increases, the rate of facilitated diffusion increases up to a maximum (Vmax) due to saturation of all carriers. Simple diffusion has no Vmax as it does not need such carrier. Prof Ahmed ElGendy Prof Ahmed ElGendy Prof Ahmed ElGendy Prof Ahmed ElGendy Prof Ahmed ElGendy Prof Ahmed ElGendy Osmosis Def: -It is passive flow of water (diffusion) across a semi-permeable (selectively permeable) membrane down a concentration gradient of water i.e from high concentration of water to low concentration of water. (or low concentration of solute to high concentration of solute). Prof Ahmed ElGendy Osmosis Solute Water Water 1 2 Prof Ahmed ElGendy Osmolarity regards only the number of molecules and disregards their chemical composition, charge or size. K+ protein ? Cl_ glucose Ca++ Na+ lipid Prof Ahmed ElGendy Prof Ahmed ElGendy Osmolarity: Normal serum (blood) osmolarity = 290-310 mosmol/L. = (5000 mmHg) Osmotic pressure:- It is the pressure needed to stop osmosis. It depends on the number of molecules of solute (not the weight). Prof Ahmed ElGendy Physiological Significance of osmosis` a) At the cellular level -The extracellular fluid (ECF) and intracellular fluid (ICF) are osmotically equal and any change in plasma osmolarity causes cells to shrink or swell. Prof Ahmed ElGendy Tonicity A term used to describe the osmolality of any solution in relation to plasma and its effect on cell volume. Therefore: ◼ Isotonic solution has the same plasma osmolality and does not change the cell volume. ◼ Hypotonic solution has less osmolality than plasma and it increases the cell volume (cell swelling). ◼ Hypertonic solution has more osmolality than plasma and it decreases the cell volume (cell shrinking). Prof Ahmed ElGendy Prof Ahmed ElGendy Physiological Significance of osmosis b) At capillary level -blood is filtered by the effect of the hydrostatic pressure (blood pressure). The filtered fluid: a) carries nutrients as glucose, amino acids and O2 to tissues b) removes metabolites as CO2 &lactic acid.. Prof Ahmed ElGendy Reabsorption Filteration Interstitial fluid Capillary Venule arteriole Prof Ahmed ElGendy Principles of membrane transport (cont.) (3) Type of transport distinguished based upon how energy is used. Prof Ahmed ElGendy B- Active transport Definition:- Transport of a substance against its electro- chemical gradient. Criteria of active transport:- two 1-Occurs against concentration (chemical), electrical or pressure gradient i.e. up hill. 2-Needs energy. Types of active transport:- 1-Primary active transport Definition:- Transport of a substance against its electrochemical gradient by a specific carrier and this carrier has ATPpase activity, i.e., hydrolyze ATP and produces energy. Prof Ahmed ElGendy Examples:- 1-Na+-K+ pump: Pump present in all cells of the body that pumps 3 Na+ to outside the cell coupled with pumping 2 K+ to the inside of the cell. 2-Calcium pump:- 2 pumps are present a-In the cell membrane and pumps Ca2+ to outside the cell. b-In the mitochondria and pumps Ca2+ to the inside of mitochondria. Through these pumps, Ca2+ is maintained at very low level intracellularly, about 10,000 times less than extracellularly. 3-H+ pump:- in the renal tubules Prof Ahmed ElGendy 2- Secondary active transport:- Definition:- Transport of a substance actively (against its electro-chemical gradient) secondary to passive transport of another substance (down its electro chemical gradient). Types:- two types 1-Co-transport (symport):- In which the two substances are transported in the same direction. Prof Ahmed ElGendy Example:- Sodium-glucose co-transport that occurs in epithelial cells of the intestine and renal tubules. In this mechanism, glucose and Na+ bind to a common carrier and glucose is carried into the cell (against its electrochemical gradient) as Na+ moves to the inside of the cell (down its electrochemical gradient). Prof Ahmed ElGendy 2-Counter transport (Antiport):- In which the two substance are transported in opposite directions. Example:- Sodium-hydrogen counter transport in the renal tubular epithelium. In this mechanism, there is a common carrier for Na+ and H+, Na+ binds to a receptor on the outer surface of the carrier and H+ binds to a receptor site on the inner surface of the carrier. H+ is carried outside the cell (against its electrochemical gradient) as Na+ moves passively to the inside of the cell (down its electrochemical gradient). Prof Ahmed ElGendy 3- Endocytosis (cell ingestion):- Definition:- is an active process by which macromolecules, e.g., protein and large particles, e.g., bacteria are transported to the inside of the cell. Types:- 2 types 1-Pinocytosis (cell drinking) It is the process by which macromolecules, e.g., proteins are transported to the inside of the cell. It is transported in a vesicle containing ECF, thus the name cell drinking. 2-Phagocytosis (cell eating) It is the process by which large particles e.g. bacteria are transported to the inside of the cell. It is transported in a vesicle containing the bacteria only without ECF, thus the name cell eating. Prof Ahmed ElGendy Prof Ahmed ElGendy Pinocytosis Phagocytosis 1-Concerned with transport of 1-Concerned with transport of large macromolecules as protiens particles as bacteria 2-The vesicle formed contain ECF 2-The vesicle formed contain NO ECF hence the name cell drinking hence the name cell eating 3-Occurs in most cells of the body 3-Occurs in some cells called phagocytic cells as neutrophils and macrophages. Prof Ahmed ElGendy 4-Exocytosis (cell excretion):- Is a process by which macromolecules and large particles are transported to the outside of the cell. It is reverse to endocytosis. Prof Ahmed ElGendy Summary Unfavorabl energy e Add Prof Ahmed ElGendy Resources ▪Guyton AC, and Hall JE (2010); Text book of medical physiology, 12th ed., W.B. Saunders Company ▪Ganong WF. (2012) ; Review of Medical Physiology, 24th ed., Lange Basic Science ▪Lauralee Sherwood (2012); Human physiology, from cell to system, 8th ed., Blackwell Press ▪www.advan.physiology.org Prof Ahmed ElGendy. Prof Ahmed ElGendy Biochemistry of proteins Proteins are macromolecules composed of polymers of covalently linked amino acids and that they are involved in every cellular process. Amino acids are not stored by the body Amino acids must be obtained from -Diet -Synthesized de novo, or N -Produced from normal protein degradation. C H S O P ⦿At physiologic pH: The side chains of lysine & arginine are fully ionized and positively charged. 20 amino acids: 9 Essential Aas cannot be manufactured by the body & 11 non-essential AAs can be manufactured by the body with proper nutrition. Alanine Glutamic Acid Lysine Threonine Arginine* Glutamine Methionine Tryptophan Aspartic Acid Glycine Phenylalanine Tyrosine Asparagine Histidine* Proline Valine Cysteine-Cystine Isoleucine Serine Leucine How to remember the essential amino acid? I Left Home To Make Isoleucine Leucine Histidine Tryptophan Methionine Visit Throught London Philipin Argantin Valine Threonine Lysine Phenylalanine Arginine Levels of Protein Structure A. Peptide bond (PB): In proteins, AAs are joined covalently by PB, which are amide linkages between the α-carboxyl group of one AA & the α-amino group of another. PBs are not broken by conditions that denature proteins (heating or high concentrations of urea). PBs are hydrolyzed by prolonged exposure to strong acid or base at elevated temperatures. Bonds contributing to tertiary structure D. Denaturation of proteins Protein denaturation results in the unfolding & disorganization of the protein's secondary & tertiary structures, which are not accompanied by hydrolysis of peptide bonds. Denatured proteins are often insoluble &, therefore, precipitate from solution. Denaturing agents Heat, Organic solvents Mechanical mixing Strong acids or bases Detergents Ions of heavy metals such as lead and mercury. Overall protein metabolism Urea Fat Glycogen Body proteins NH3 Glucose Dietary Carbon CO2 + Amino acid pool ~ H2O + proteins skeleton 100 g energy Ketone bodies Synthesis of non-essential amino ▪ acids Heme ▪ Fat, sterol Creatine ▪ Purines ▪ Pyrimidines ▪ Neurotransmitters ▪ Hormones ▪ Melanin ▪ Niacin ▪ Other nitrogenous compounds A. Glucogenic amino acids Amino acids whose catabolism yields pyruvate or one of the intermediates of the citric acid cycle are termed glucogenic or glycogenic. These intermediates are substrates for gluconeogenesis and, therefore, can give rise to the net formation of glucose or glycogen in the liver and glycogen in the muscle. B. Ketogenic amino acids Amino acids whose catabolism yields either acetoacetate or one of its precursor, (acetyl CoA or acetoacetyl CoA) are termed ketogenic. Acetoacetate is one of the ketone bodies, which also include 3-hydroxybutyrate and acetone. Leucine and lysine are the only exclusively ketogenic amino acids found in proteins. Their carbon skeletons are not substrates for gluconeogenesis and, therefore, cannot give rise to the net formation of glucose or glycogen in the liver, or glycogen in the muscle. C. Both glucogenic and ketogenic Isolucine, phenylalanine, tyrosine and tryptophan are glucogenic and ketogenic amino acids as part of its carbon skeleton can give glucose, the other can give ketone bodies Most of the nitrogen in the diet is consumed in the form of protein, typically amounting from 70 to 100g/day. Proteins are generally too large to be absorbed by the intestine. They must, therefore, be hydrolyzed to yield their constituent amino acids, which can be absorbed. Proteolytic enzymes responsible for degrading proteins are produced by three different organs: the stomach, the pancreas, and the small intestine Gastric Digestion Function of acidic pH Kills bacteria Denatures proteins Activation and Action of Pepsin Intestinal Digestion Pancreatic enzymes Intestinal enzymes 2. Pepsin – It is secreted by the chief cells in the form of inactive zymogen, pepsinogen. Pepsinogen is activated by HCl then by autocatalytic activation. HCl – Pepsinogen ⎯⎯⎯⎯⎯ → Pepsin – It is an endopeptidase with broad specificity, it is more specific to peptide bonds containing the carboxylic groups of aromatic amino acids (phenylalanine, tyrosine and tryptophan). Pepsin splits denatured proteins into large polypeptides. In the small intestine Digestion in small intestine is due to the action of proteases present in both pancreatic and intestinal secretions. Pancreatic enzymes Pancreatic proteases are stored in proenzyme form in the pancreas. Pancreatic proteases have an optimum pH of 6-8. 1. Trypsin – Trypsin also activates other zymogens (chymotrypsinogen, proelastase and procarboxypeptidase). Trypsin is an endopeptidase ,acts specifically on peptide bonds connected to the carboxylic group of basic amino acids (arginine and lysine). Intestinal enteropeptidase Trypsinogen Trypsin Dietary protein Pepsin Polypeptides and amino acids Stomach Trypsin Chymotrypsin Carboxypeptidase Elastase To liver Pancreas Oligopeptides and amino acids Aminopeptidases Small intestine Tripeptidase Dipeptidase Amino acids Digestion of dietary proteins by the proteolytic enzymes of the gastrointestinal tract. Overall metabolism of nitrogen Nitrogen intake Nitrogen forms about 16% of proteins; normally one takes about 90 g of proteins, i.e., 14.5 g of nitrogen, daily. Nitrogen output After absorption, the amino acids of food proteins undergo many metabolic reactions. They are finally catabolized , chiefly by deamination, and their nitrogen is excreted through: urine, stools and other routes. Nitrogen balance The nitrogen balance is the quantitative difference between the nitrogen intake and output. Since most of the nitrogen of the diet is protein nitrogen, and most of the nitrogenous excretory products are derived from protein catabolism, the balance between the two represents the balance between protein anabolism and catabolism. Three States may exist: 1- Nitrogen equilibrium. 2- Positive nitrogen balance. 3- Negative nitrogen balance. Nitrogen equilibrium It exists when output equals intake. It occurs in the normal healthy adult on an adequate diet. 1- Positive nitrogen balance It exists when intake exceeds output. It occurs whenever new tissues are built, e.g., during growth, pregnancy, muscular training. 2. Negative nitrogen balance: as Inadequate protein intake – starvation, malnutrition, and gastrointestinal diseases. Loss of protein: as chronic hemorrhage, albuminuria, and during lactation, Increased protein catabolism – Also in diabetes mellitus, Cushing's syndrome, hyperthyroidism, and infectious fevers. Transamination reactions The enzymes that catalyze this type of reaction are called aminotransferases and also called transaminases. They are present in the CYTOSOL and mitochondria of all tissues especially the liver. Transamination is the transfer of an amino group usually from an α-amino acid to an α-keto acid forming a new α-amino acid and a new α-keto acid. R.CH.COOH HOOC.CH2.CH2.C.COOH I II NH2 O transaminase α-Amino acid α-Ketoglutaric acid R.C.COOH HOOC.CH2.CH2.CH.COOH II I O NH2 α-Keto acid Glutamic acid 1. Alanine aminotransferase – The reaction is readily reversible. However, during amino acid catabolism, this enzyme functions in the direction of glutamate synthesis. CH3.CH.COOH HOOC.CH2.CH2.C.COOH I II NH2 O Alanine Alanine transaminase α-Ketoglutaric acid CH3.C.COOH HOOC.CH2.CH2.CH.COOH II I O NH2 Pyruvic acid Glutamic acid 2. Aspartate aminotransferase (AST) – aminotransferases funnel amino groups to form glutamate. During amino acid catabolism, AST transfers amino groups from glutamate to oxaloacetate, forming aspartate, which is used as a source of nitrogen in the urea cycle. HOOC.CH2.CH.COOH HOOC.CH2.CH2.C.COOH I II NH2 Aspartate O Aspartic acid transaminase α-Ketoglutaric acid HOOC.CH2.C.COOH HOOC.CH2.CH2.CH.COOH II I O NH2 Oxaloacetic acid Glutamic acid Diagnostic value of plasma aminotransferases Aminotransferases are normally intracellular enzymes, with the low levels found in the plasma representing the release of cellular contents during normal cell turnover. The presence of elevated plasma levels of aminotransferases indicates damage to cells rich in these enzymes. Two aminotransferases AST and ALT are of particular diagnostic value when they are found in the plasma: 1. Liver disease: Plasma AST and ALT are elevated in nearly all liver diseases, but are particularly high in conditions that cause extensive cell necrosis, such as severe viral hepatitis, toxic injury, and prolonged circulatory collapse. 2. Nonhepatic disease: Aminotransferases may be elevated in nonhepatic disease, such as myocardial infarction and muscle disorders. Transport of ammonia to the liver Two mechanisms are available in humans for the transport of ammonia from the peripheral tissues to the liver for its ultimate conversion to urea: 1. The first, found in most tissues, uses glutamine synthetase to combine ammonia with glutamate to form glutamine,a nontoxic transport form of ammonia. The glutamine is transported in the blood to the liver where it is cleaved by glutaminase to produce glutamate and free ammonia. 2. The second transport mechanism, used primarily by muscle, involves transamination of pyruvate (the end-product of aerobic glyclosysis) to form alanine.Alanine is transported by the blood to the liver, where it is converted to pyruvate, again by transamination. In the liver, the pathway of gluconeogenesis can use the pyruvate to synthesize glucose, which can enter the blood and be used by muscle,a pathway called the glucose-alanine cycle. From most tissues Urea H2O Glutamine Glutaminase Liver NH3 Glutamate dehydrogenase Glutamate α-ketoglutarate ALT Alanine Pyruvate Glucose From muscle Alanine cycle Mechanism of ammonia toxicity Glucose The toxicity is thought to result, in part, from a Glycolysis shift in the equilibrium of the glutamate dehydrogenase reaction towards the direction of Pyruvate glutamate formation. This depletes α-ketoglutarate, an essential Oxaloacetate Acetyl CoA intermediate in the citric acid cycle, resulting in a decrease in cellular oxidation and ATP production. Citrate TCA The brain is particularly sensitive to hyperammonemia, because it depends on the NAD NH3 NADH Isocitrate NH3 citric acid cycle to maintain its high rate of energy Glutamine Glutamate α-ketoglutarate production. ADP ATP NAD NADH Urea cycle This is the principal pathway of disposal of ammonia resulting from the deamination of amino acids. It allows the body to get rid of about 80-90% of the amino groups of amino acids in a neutral non-toxic form. Urea has no role in animal metabolism other than an end product that is excreted. Urea formation occurs only in the liver. Only the first 2 reactions occur in the mitochondria, all subsequent 3 reactions occur in the cytosol. Mitochondrion 1 2 ATP + HCO3- + NH3 Carbamoyl phosphate + 2 ADP + Pi Pi Ornithine 2 Citrulline Citrulline Ornithine Urea cycle ATP 3 Aspartate Urea 5 AMP + PPi H2O Arginino- Arginine succinate 4 Cytosol Fumarate Malat Oxaloacetate e Hyperammonemi a The capacity of the hepatic urea cycle exceeds the normal rates of ammonia generation, and the levels of serum ammonia are normally low (5 to 50 pmol/L). However, when the liver function is compromised, due either to genetic defects of the urea cycle, or liver disease, blood levels can rise above 1000 mmol/L. Such hyperammonemia is a medical emergency, because ammonia has a direct neurotoxic effect on the CNS.. Vitamins By Prof.Dr/ Amal Shehata DR/ Nevin alazhary I. Overview Vitamins (Vit) ar