McCance exam 2

Committed Stem Cells & Growth/Differentiation Inducers

• Committed stem cells are derived from multipotential hematopoietic stem cells
• They include CFU-E (colony-forming unit–erythrocyte) for erythrocytes; CFU-GM for granulocytes and monocytes
• Growth inducers are proteins promoting committed stem cell growth and reproduction
• Interleukin-3 promotes growth and reproduction of virtually all committed stem cell types
• Differentiation inducers cause committed stem cells to differentiate toward specific adult blood cell types

RBC Differentiation Stages

• Proerythroblast: The initial, identifiable red blood cell (RBC) precursor
• Basophil erythroblast: The first-generation cells staining with basic dyes
• Polychromatophil erythroblast: The stage at which hemoglobin first appears inside the cell
• Reticulocyte: An immature RBC containing basophilic material like Golgi apparatus, mitochondria, and some cytoplasmic organelles
• Diapedesis is the process of reticulocytes passing from bone marrow into blood capillaries by squeezing through capillary pores
• Erythrocyte: A mature RBC that forms after remaining basophilic material disappears within 1–2 days

Erythropoietin & RBC Production Regulation

• Erythropoietin controls RBC production, responding to tissue oxygenation levels
• It's mainly produced in the kidneys (90%) and liver (10%)
• Erythropoietin ensures sufficient RBC numbers for adequate oxygen transport and prevents overabundance that impedes blood flow

Factors Decreasing Oxygenation

• Low blood volume
• Anemia
• Low hemoglobin
• Poor blood flow
• Pulmonary disease

RBC Production Stimulus

• The principal stimulus for RBC production is erythropoietin, a circulating glycoprotein hormone stimulated by low oxygen states
• Renal tissue hypoxia increases hypoxia-inducible factor-1 (HIF-1) levels
• HIF-1 binds to a hypoxia response element in the erythropoietin gene to increase production

Vitamin B12 & Folic Acid Importance

• Vitamin B12 and folic acid are essential for DNA synthesis and RBC maturation
• A deficiency leads to maturation failure anemia

Hemoglobin Formation

• The formation of hemoglobin begins in polychromatophil erythroblasts and continues in reticulocytes
• Hemoglobin is formed from succinyl-CoA, glycine, and iron

Hemoglobin A Composition

• Hemoglobin A is a combination of two alpha chains and two beta chains

Iron Metabolism

• Total body iron: 4-5g, mainly in hemoglobin (65%)
• Iron is stored as ferritin and hemosiderin and transported by transferrin

RBC Lifespan

• RBCs circulate for about 120 days before destruction

Blood Loss Anemia

• It is characterized by low RBC concentration following hemorrhage

Aplastic Anemia

• This is caused by failure of the bone marrow

Megaloblastic Anemia

• Vitamin B12 or folic acid deficiency can cause this anemia

Hemolytic Anemia

• This is caused by fragile RBCs that rupture easily

Secondary Polycythemia

• This is a response to hypoxia

Polycythemia Vera

• This is caused by the genetic overproduction of RBCs

Circulatory Effects of Polycythemia

• Increased blood viscosity leads to sluggish blood flow and reduces venous return
• Increased blood volume increases venous return
• Cardiac output remains near normal due to balanced effects
• Hypertension occurs in about one-third of individuals due to the failure of compensatory mechanisms

Blood Antigens and Immune Reactions

• Blood transfusion reactions occur due to antigen-antibody interactions

ABO & Rh Systems

• The ABO and Rh systems are the most significant for transfusion compatibility

Agglutinogens

• Agglutinogens: A and B antigens on RBC surfaces and determine blood type

Blood Type O

• No A or B antigens

Type A Blood

• Only A antigen

Type B Blood

• Only B antigen

Type AB Blood

• Has both A and B antigens

Agglutinins

• Antibodies (IgM, IgG) in plasma targeting non-self blood antigens are formed after exposure to environmental antigens

Agglutination

• Antibodies causing RBCs to clump together

Hemolysis

• Destruction of agglutinated cells, releasing hemoglobin

Rh-Positive

• Presence of D antigen makes the blood

Rh-Negative

• Absence of D antigen makes the blood
• Anti-Rh antibodies form after exposure to Rh-positive blood

Erythroblastosis Fetalis

• Occurs when an Rh-negative mother carries an Rh-positive fetus
• Maternal anti-Rh antibodies cross the placenta, attacking fetal RBCs

Hemostasis

• Prevention of blood loss involving vascular constriction, platelet plug formation, blood clot formation, and fibrous tissue growth

Platelet Characteristics

• Formed from megakaryocytes in bone marrow
• Contain contractile proteins, enzyme systems, and calcium stores
• A glycoprotein coat enables adherence to damaged vessels

Extrinsic Pathway

• It is initiated by tissue trauma and the release of tissue factor

Intrinsic Pathway

• It is triggered by blood trauma or contact with collagen

Common Pathway

• This culminates in the formation of prothrombin activator which turns into Thrombin, then Fibrin

Clot Retraction & Organization

• Platelets contract, tightening the clot
• Fibroblasts invade, forming connective tissue

Anticoagulants

• Antithrombin III: Inactivates thrombin
• Heparin: Enhances antithrombin III activity
• Protein C: Inactivates factors V and VIII

Plasmin & Clot Lysis

• Plasminogen: Converted to plasmin by tissue plasminogen activator (tPA)
• Plasmin: Digests fibrin, dissolving clots

Vitamine K Deficiency

• results in impaired synthesis of clotting factors II, VII, IX, X.

Hemophilia

• Deficiency of clotting factor VIII (Hemophilia A) or IX (Hemophilia B)

Thrombocytopenia

• Low platelet count leading to poor clot formation

Musculoskeletal Development: Bone Formation

• Begins around sixth week of gestation
• Includes delivery of bone cell precursors to formation sites and aggregation of these cells at primary ossification centers

Bone Formation Types

• Intramembranous: Occurs within the mesenchyme, forming bones like the cranium and clavicles; mesenchyme vascularization leads to osteoblast aggregation and solid bone formation
• Endochondral: New bone develops from cartilage; mesenchymal tissue forms a cartilage anlage and blood vessel invasion brings osteoprogenitor cells, leading to primary calcification centers

Bone Growth

• Long bone length increases at the physeal plate through endochondral ossification
• Cartilage cells multiply on the epiphyseal side
• Growth hormone stimulates the growth plate
• Peptide factors, cell interactions, extracellular matrix, nutrition, and hormones affect epiphyseal plate growth

Skeletal Development

• Axial skeleton shape changes during growth; newborns have a kyphosed spine and cervical spine develops a lordotic curve as the infant gains head control
• The lumbar spine's lordotic curve develops with sitting
• The appendicular skeleton grows faster than the axial skeleton in childhood

Syndactyly

• Most common upper extremity congenital defect where webbing of fingers occurs and is surgically corrected between 6 months and 1 year
• Complex cases may involve bone and nail fusion

Developmental Dysplasia of the Hip (DDH)

• Abnormal development of the proximal femur and/or acetabulum
• Risk factors: Family history, female gender, and breech presentation
• Clinical signs: Asymmetry of gluteal folds and limited hip abduction
• Barlow and Ortolani maneuvers are diagnostic tools
• Treatment includes a Pavlik harness for infants younger than 6 months

Foot Deformities

• Congenital foot deformities are found in approximately 4% of newborns
• Metatarsus Adductus: Forefoot adduction deformity; mild cases often self-correct; severe cases may require serial casting
• Clubfoot (Equinovarus Deformity): The foot turns inward and downward requiring the Ponseti casting technique
• Pes Planus (Flatfoot): Most babies are born with flat feet; asymptomatic flexible flatfoot does not require treatment

Osteogenesis Imperfecta (OI)

• Collagen-related bone dysplasia causing increased fracture rate and bone deformation; the Sillence classification categorizes OI based on inheritance and clinical presentation
• Evaluation is based on clinical signs and can be diagnosed prenatally

Rickets

• The failure of growing bone to mineralize, leading to soft bones and skeletal deformity due to insufficient vitamin D causes symptoms like hypotonia and muscle weakness

Scoliosis

• The rotational spine curvature can be nonstructural or structural
• Structural scoliosis cases are idiopathic and diagnosed by radiographic examination

Osteomyelitis

• Bone infection often affecting children ages 3–12, where bacteria enter through the bloodstream and lodge in the medullary cavity, with the causative microorganism varying with age

Legg-Calvé-Perthes (LCP) Disease

• Interrupted blood supply to the femoral head

Osgood-Schlatter Disease

• Tendinitis of the anterior patellar tendon and osteochondrosis of the tibial tubercle

Cerebral Palsy (CP)

• Nonprogressive movement and posture disorders from injury or malformation of the developing central nervous system

Neuromuscular Disorders

• Inherited disorders causing progressive muscle fiber loss; Duchenne muscular dystrophy (DMD) and spinal muscular atrophy (SMA) are the most prevalent

Sarcomere Structure & Function

• Muscle fibers contain myofibrils made of actin (thin, light I band) and myosin (thick, dark A band)
• The sarcomere is the fundamental myocyte contraction unit, located between Z discs
• Myosin filaments contain a tail, hinge, and head; tails bundle together for a thick appearance
• The myosin filament's arm and head form the crossbridge, which contain two hinges to facilitate head movement

Muscle Contraction Process

• ATP binds, causing the myosin molecule to extend into an open position
• An action potential prompts calcium release from the sarcoplasmic reticulum, enabling myosin filament heads to attach to active sites
• The myosin head tilts, dragging the actin filament along in a power stroke, bringing the filaments closer together
• ATP is used to extend the myosin head, storing energy like a stretched spring
• Released energy allows the myosin head to attach and contract when calcium is present

Muscle Contraction Energy Sources

• ATP is needed for the walk-along mechanism, pumping calcium into the sarcoplasmic reticulum, and the sodium-potassium pump
• Phosphocreatine, in small muscle cell amounts, has a higher energy phosphate bond than ATP and can create ATP for approximately 5–8 seconds

Creatine Supplementation

• Provides energy for only about 5 to 8 seconds
• It has the smallest effect on oxidative metabolism, glycolysis, and creatine

Types of Muscle Contractions

• Isometric contraction: Tension in the muscle without shortening it
• Isotonic contraction: Muscle shortening while tension remains constant

Muscle Fiber Types

• Slow/red fibers have myoglobin and capillaries for oxygenation, enabling sustained tension
• Fast muscle fibers are larger, providing greater contraction strength, extensive sarcoplasmic reticulum for rapid calcium release, and enzymes for glycolysis
• Every muscle contains a mixture of fast and slow fibers

Motor Units & Force Generation

• Motor neurons in the spinal cord's anterior horn innervate muscle fibers, forming motor units
• Fine motor control requires fewer muscles per motor neuron, larger muscles for strength have more motor units per neuron.
• Force can be increased through summation, involving increasing motor units or contraction frequency

Tetany

• Occurs when the frequency of contraction increases to the point where contractions fuse together

Muscle Remodeling & Hypertrophy

• Hypertrophy results from an increased number of actin and myosin filaments due to strong contractions
• New sarcomeres are added when muscles are stretched, and sarcomeres are removed when a muscle remains shortened for an extended period

Neuromuscular Junction & Skeletal Muscle Excitation

• Large myelinated nerve fibers rapidly transmit signals from the spinal cord's anterior horn to skeletal muscle fibers
• An action potential travels down the motor neuron, causing a change in electrical potential
• Sodium channels open, allowing sodium to flow in and create a positive electrical change
• At the end of the neuron, a voltage-gated calcium channel opens, allowing calcium to diffuse into the motor endplate
• Calcium binds with vesicles containing neurotransmitters, primarily acetylcholine, causing them to bind with the membrane and release the neurotransmitter
• Acetylcholine diffuses across the neuromuscular junction and binds to ligand-gated sodium channels, depolarizing the muscle

Acetylcholine Role

• Two acetylcholine molecules attach to a specific portion of the sodium ion channel, opening it and allowing diffusion into the muscle
• Rapid sodium influx changes the muscle membrane's electronegativity from negative to positive, propagating the action potential
• The change in potential causes voltage-gated receptors on the sarcoplasmic reticulum to open, releasing calcium into the muscle
• Acetylcholine must be removed to allow the sodium channel to close, primarily via acetylcholinesterase, which breaks down acetylcholine into choline and acetate

Drugs Affecting Neuromuscular Transmission

• Drugs can alter electronegativity, affecting stimulus required to reach action potential threshold
• Succinylcholine: Acts like acetylcholine, binding to the acetylcholinesodium receptor and opening the channel, causing depolarization but may cause muscle pain
• Rocuronium: An acetylcholine receptor antagonist, blocking the channel and causing paralysis without fasciculations

T-Tubules & Sarcoplasmic Reticulum

• T-tubules facilitate rapid action potential spread throughout the muscle
• The sarcoplasmic reticulum, next to T-tubules, is where calcium is stored and released
• A voltage change in the t-tubule is sensed by ryanodine receptor channels in the sarcoplasmic reticulum, causing the opening and release of calcium channels
• Calcium is pumped back into the sarcoplasmic reticulum by a calcium pump located in its walls

Malignant Hyperthermia

• A mutation in the ryanodine receptor can cause malignant hyperthermia
• Exposure to certain anesthetics or succinylcholine can cause the opening of calcium channels and continuous muscle contraction, leading to hyperkalemia and elevated temperature

Smooth Muscle

• Multi-unit smooth muscle fibers operate independently, often innervated by a single nerve fiber; unitary smooth muscle fibers contract together in sheets or bundles
• Prolonged tonic contraction is characteristic of smooth muscle, with slower myosin cross-bridge cycling and increased attachment time, requiring less energy
• It can be stimulated by stretch, nerve stimulation, hormones, or chemical environment changes Smooth muscle does not contain troponin; instead, calcium combines with calmodulin, activating myosin light chain kinase, leading to myosin attachment to actin

Smooth Muscle Nerve Stimulation

• Nerves, hormones, local chemicals, and stretch can stimulate smooth muscle
• Neuromuscular junctions in smooth muscle are branched, with neurotransmitters released outside the muscle to diffuse to receptors
• Vesicles in smooth muscle neurons can contain acetylcholine, norepinephrine, or epinephrine
• The action is determined by the stimulated receptor, so drugs can cause different effects in different locations
• Acetylcholine can be inhibitory or excitatory in different muscles

Musculoskeletal Injuries & Healing

Unintentional traumatic injuries are a leading cause of death for people aged 1 to 44

• Fractures can be complete or incomplete, open or closed, and have various patterns such as transverse, spiral, or greenstick
• Fracture healing occurs in three phases: inflammatory, repair, and remodeling
• Subluxation is a partial loss of contact between two joints, while dislocation is a temporary displacement of a bone.

Strains vs Sprains

• A strain is a tear or injury to a tendon while a sprain is a tear or injury to a ligament.
• The inflammatory cascade begins immediately after an injury, with collagen formation starting 3 to 4 days later

Rhabdomyolysis

• Break down of muscle that releases contents that can block the kidney and can cause hyperkalemia, metabolic acidosis, and potential DIC
• IV hydration is a treatment to dilute the muscle contents and prevent them from binding in the glomerulus

Musculoskeletal Diseases

• Osteoporosis is characterized by low bone mineral density, impaired integrity, decreased strength, and increased fracture risk
• Osteomyelitis is a bone infection typically caused by bacteria, leading to inflammation, necrosis, and potential antibiotic treatment or debridement
• Ankylosing spondylitis is a chronic inflammatory joint disease that can cause fusion of the spine and sacroiliac joints, potentially leading to difficult intubation
• Scoliosis involves curvature and rotation of the spine, which can complicate epidural placement

Musculoskeletal Condition in Children

• Bone formation begins in the 6th week of gestation. Syndactyly is the presence of multiple digits.
• Hip dysplasia can occur during birth, involving subluxation, dislocation, or acetabular dysplasia
• Rickets is a failure of bone to become mineralized due to vitamin D insufficiency or insensitivity
• Cerebral palsy is a non-progressive disorder of movement and posture resulting from injury or malformation of the CNS, often with comorbid conditions
• Duchenne's muscular dystrophy (DMD) is characterized by the absence of dystrophin, leading to muscle weakness, loss of ambulation, and potential anesthetic complications

Musculoskeletal Injuries: Muscle Cell Injuries

Unintentional traumatic injuries are a leading cause of death for people aged 1-44

Types of Fractures

• Complete Fracture: Bone is broken into pieces
• Incomplete Fracture: Bone is not completely broken (e.g., greenstick fracture)
• Open Fracture: Bone breaks through the skin
• Closed Fracture: Skin remains intact
• Greenstick Fracture: Perforates one cortex and splinters spongy bone
• Transverse Fracture: Horizontal break through the bone
• Spiral Fracture: Curves around the bone, caused by twisting

Common fractures

Greenstick, transverse, spiral, the highest incidence occur in young males (15-24) and adults over 65

Fracture Healing

• Process: Bleeding from the bone damage forms a hematoma. Necrotic tissue and debris cause an inflammatory response. Platelet-derived growth factor, prostaglandins, and other factors promote healing. Osteoblasts and osteoclasts are activated
• Phases: Inflammatory, repair, and remodeling.
• Callus Formation: Occurs prior to remodeling

Complications of Fractures

• Nonunion: Failure of bone ends to unite
• Delayed Union: Healing occurs after 8-9 months
• Malunion: Healing in a non-anatomical position

Fracture Treatment

• Realignment: Manipulating bone fragments to the correct position
• Immobilization: Holding the bone in place for healing
• Traction: Used to maintain alignment
• Open Reduction Internal Fixation (ORIF): Surgical procedure to align fragments with hardware
• External Fixation: Device used to stabilize fractures

Dislocation and Subluxation

• Dislocation: Temporary displacement of a bone from its joint; a complex dislocation involves a fracture
• Subluxation: Partial loss of contact between joint surfaces
• Common Sites: Shoulder, elbow, wrist, finger, hip, and knee

Tendon and Ligament injuries

• Tendons: Attach muscle to bone
• Ligaments: Connect bones at a joint
• Strain: Tear or injury to a tendon
• Sprain: Tear or injury to a ligament
• Avulsion: Complete separation of a tendon or ligament from its bony attachment
• Healing: Inflammation occurs, followed by collagen formation where the tendon or ligament lacks sufficient strength for 4-5 weeks

Tendonitis and Bursitis

• Trauma and overuse can cause inflammation of tendons (tendonitis), painful degradation of collagen fibers (tendinosis), and inflammation of bursae (bursitis)

Rhabdomyolysis

• Rapid breakdown of muscle releasing intracellular contents into the bloodstream and can be caused by trauma or overuse

Rhabdomyolysis Complications

• Hyperkalemia, metabolic acidosis, acute renal failure, and possible DIC
• Treatment: IV hydration, hemodialysis, and management of disseminated intravascular coagulation (DIC)

Bone Disorders

• Osteoporosis: Low bone mineral density, impaired bone structure, and increased fracture risk; with prevention being key
• Risk factors are not necessarily a consequence of aging; with prevention with calcium, intake (1000-1500mg/day), high intake of fruits and vegetables

Osteomyelitis

• Infections of the bones caused by bacteria, fungi, mycobacteria, parasites, or viruses which occur from both Endogenous (from pathogens in the blood), and Exogenous (from external sources)
• Bone Infections need antibiotics, debridement, surgery hyperbaric oxygen therapy

Joint Disorders

• Rheumatoid Arthritis: Autoimmune destruction of synovial membranes and joints
• Ankylosing Spondylitis: Chronic inflammatory disease causing stiffening and fusion of the spine and sacroiliac joints.

Skeletal Muscle Disorders

• Weakness and Fatigue: Common symptoms that can result from a lack of motion, stress, or disuse atrophy with Myotonic and Periodic Paralysis.

Fracture Types

• Complete: Bone breaks into separate pieces
• Incomplete: Bone damaged but remains in one piece
• Open: Break in skin near the fracture site
• Closed: No break in the skin

Fracture Line Classifications

• Comminuted: Multiple bone fragments
• Linear: Fracture line runs parallel to the long axis of the bone
• Oblique: Fracture line is at an angle to the long axis of the bone
• Spiral: Fracture line encircles the bone
• Transverse: Fracture line is perpendicular to the long axis of the bone
• Impacted: Fracture fragments are pushed into each other
• Pathologic: Occurs at a point in the bone weakened by disease
• Avulsion: A fragment of bone connected to a ligament or tendon separates from the main bone
• Greenstick: Break in only one cortex of bone

Fracture Healing Process

• Three overlapping phases occur with an Inflammatory phase lasting 3-4 days, a Repair Phase with tissue formation, followed by osteoblasts synthesizing collagen and matrix to form callus
• The final is a Remodeling Phase, where unnecessary callus is resorbed and trabeculae are reformed along stress lines, lasting months to years

Clinical Manifestation of Fractures

• Include impaired function, unnatural alignment, swelling, muscle spasm, tenderness, pain, and impaired sensation
• Treatment: Closed or open reduction is needed where open is a surgical procedure the exposes fracture site, realigns fragments, and maintain with hardware.

Sprains and Strains

• Sprain: Injury to a ligament
• Strain: Injury to a tendon
• Avulsion: Complete separation of a tendon or ligament from its bony attachment

Patho of Sprains and Strains

• An inflammatory process starts, with collagen formation initially random but is organized parallel to stress lines within 3-4 days
• Clinical Manifestations: Pain, functional limitation, swelling, changes contour, and possible dislocation or subluxation

Tendipathies

• Tendinopathy: Inflammation of a tendon, most tendon pathology is caused by tissue degeneration rather than inflammation
• Bursitis: Inflammation of bursae where common sites are Shoulder, hip, knee, and elbow

Rhabdomyolysis (cont)

• Rapid muscle breakdown causing the release of myoglobin into blood stream with causes due to trauma, genetic, medications, and intoxication
• Includes hyperkalemia, kidney failure, dark urine, and muscle pain
• Evaluation: Serum Creatine Kinase is the most important

Bone Disorders: Osteoprosis

• Characterized by low density and increased fracture risk
• With risk factors of inactivity and malnutrition, the proper treatment is calcium/vitamine D and weights

Osteomyelitis (Cont)

• A bone infection that causes inflammation and abscess formation and requires surgical and antibiotic therapy

Anemia Overview: In Children

• Commonly results from on of four disabilities and is most common cause is iron deficiency
• Has symptoms of fatigue, dizziness, and low HB

Acute Blood Loss Overview

• The physiological affect of acute blood loss in reduced intravascular volume and depends on rate of hemorrhage and can cause cardiovascular collapse and death
• Recovery takes up to a few months; where plasma is replaced within a day then blood within weeks

Megaloblastic Anemia

• Vitamin B12 and nutritional deficiency
• Small Erythrocytes with abnormal amount of hb
• Inefficient iron take causes this
• Hematopoietic Failure

PV

• Increased blood with no stimulus that causes peak incidence between the ages of 60-80.

Platelet Disorders

• Quantitative: Platelets
• Qualitative: Platelets

Coagulation Overview: The role of the liver?

• Defect in clotting causes liver disease
• Coagulation of clotting factors. Heparin replaces factors of DIC, which may cause blood.
• Hypercoagulability: Defect in proteins involved in the hemistat

AA

• Results in pancytopenia and can be acquired and inherited which can cause diminished level of erythrocytes and leuocycte where diagnosis would be through blood test

Characterization of Premature Blood destruction

• Congenital or hereditary and requires blood tests and bone testing where proper treatment requires different solutions

MRBC

• Over production of blood cells which includes PV and bone analysis and can lead to fatigue head and body pain that can be helped with the proper treatment

Iron Overload

• HH or too much blood can cause genetic testing and the proper care would be getting treatment.

Tormbocytopenia

• Less than 150% platelets leads to increased Hemorrhage that is a chain reaction where treatment can be the right drugs/tests

Impaired hemostatis

• Not having enough vitamin K and lead to the failure of this system

AA In Depth

• Results from hematopoietic failure resulting in Pancytopenia.
• The causes include stem, immune deficiencies or other
• Treatmemnt requires transplant, immunosuppression, or even supportive care

HA IN depth

• Characterized by premature destruction either episodes or continuous and are warm auto immune or Drug induced
• Warm-IgG, Cold-igm, Cold Hemoylsin-Exposure
• Require a removal, steroids, fluid, and blood testing.

BloodCell inDepth

• Overproduced because the over regulation of Hematopoietic
• Leads to splenomeagaly, pain, and headache from increased volume

IOL In Depth

• Hereditary or increased with Iron, requires phlebotomy, avoidance of iron and proper moderation

Low platelets

• Requires platelet creation and increased consumption

HIT

• After heparin treatment, is where problems occur and will tests for any anti platelet reactions