Neuro

Hemorrhages

• epidural - convex, compress brain

  • Could be subacute

• Subdural - concave, follow shape of skull

• Subarachnoid - hard to see on CT, busted circle of willis

  • Aneurysm

• Intracerebral

  • Acute/non-acute

    • Acute is a stroke

• (STROKE/CVA) - medical emergency, CT in 45 min

  • Hemorrhagic - 15%, arterial hypertension

    • DO NOT GIVE TPA

    • No real shape on CT, just a whiteish blob that compresses the brain

  • Ischemic - 85%, due to atherosclerosis or thromboembolism

    • GIVE TPA WITHIN 4 HOURS (from last known normal)

    • Embolic - floating clot gets stuck

      • A fib

    • Thrombotic - blood clot forms in the vessel

      • atherosclerosis - large clot

      • lacunar infarction - small occlusion

    • systemic hypo-perfusion

      • low pressure due to overflow of vasodilators (sepsis, heart failure, MI, shock, drugs)

      • Watershed infarcts with tissue necrosis

  • Clinical presentation depends on site

    • middle cerebral artery is most common

TBI*

• Occurs at the time of trauma (direct, rapid acceleration/deceleration, blast waves, penetrating injury)

  • “Welcome to the knife and gun club”

  • Coup-Countercoup injury usually

• Brain Concussion

  • mildest form

• Brain Contusion/Bruise

  • pain, residual issues or may not be long standing

• Laceration

Diffuse Axonal Injury (DAI)*

• Diffuse axonal injury - the shearing of white matter tracts due to sudden acceleration/deceleration

• Grey and white have different densities

  • Axons in white matter get stretched, twisted, or torn

• PERMANENT DAMAGE

Spinal Cord

• Neck and spinal cord injuries can also happen in a acceleration/deceleration injury

• Hyperextension: too far forward, can rupture ventral neurons

• Hyperflexion: too far back, can rupture dorsal neurons

• Step 1: secure the neck with a C-collar

CNS Infections

• Can be transmitted all types of ways - from the blood stream (hematogenous), nerve, adjacent structures, penetrating trauma

• Cerebral abscess exist (usually bacterial)

Med term

• Encephalitis - brain

  • Can be localized (HSV) or diffuse (west nile) (virus invades neurons or glial cells)

• Myelitis - diffuse infection of spinal cord

  • Polio

• Meningitis - meninges (dura, arachnoid, pia)

  • Most commonly viral

    • CSF shows high WBCs, high protein, normal glucose

  • Bacterial (see bacterial for bacteria)

    • CSF shows high WBCs, high protein, LOW glucose

  • Patients typically have pain in eyes or in head movement

  • chin-to-chest test

• Encephalomyelitis - brain and spinal cord

Bacterial

• Streptococcus pneumoniae - adult meningitis

• Group B streptococci (vaginal tract) - neonatal meningitis

  • neonates exposed during vaginal delivery

• Neisseria meningitidis - meningitis in infants, children, and teens

  • Outbreaks for peeps in close quarters (military, college)

  • Vaccine

• TB - reminder TB can infect any where and its only contagious if you are exposed to that thing

• Treponema Pallidum - syphilis which can affect the brain if untreated (neurosyphilis)

  • stage one of syphilis: painless lesions

  • Neurosyphilis is a meningeal infiltration with Bs/Ts and plasma cells, meninges become fibrotic and compress on the nerves leading to atrophy. Decreased blood flow to the brain also occurs resulting in necrosis leading to motor and mental deterioration

Viral

• Primarily transmitted in the blood

• measles, rubella, adenovirus are the ones you usually see in peds

• Mr. Worldwide (ubiquitous) Viruses - typically affect the CNS in immunocompromised

  • HSV (herpes)

    • Most common cause of viral encephalitis

  • CMV (cytomegalovirus)

  • Japanese B encephalitis - most common cause of epidemic encephalitis

  • West Nile virus makes up 10-20% of encephalitis cases and precedence is increases in the US

• Neurotropic virus (only affect neurons)

  • St. Louis encephalitis

  • Rabies

    • Fatal in unvaccinated

    • If you get bit you are treated with IgG and the vaccine

      • the immunoglobulin gives you time to build adaptive immunity with the vaccine

• AIDS related CNS infections

  • AIDS dementia is typically caused when HIV infects macrophages and CD4s, the virus is taken to the CNS and the infected cells secrete cytokines that are toxic to the brain

  • Additionally now the patient is prone to other infections because the BBB is weaker

Protozoal

• Toxoplasma gondii

  • Typically seen in neonates

  • CT shows ring enhancing lesions

  • most common protozoal infection in US

Fungal

• Fungal infections in the CNS typically only occur in immunocompromised patients

  • Candida albicans

  • Aspergillus flavus

  • Cyptococcus neoformas

Prions

• Prions are weird proteins that legit cannot be destroyed

• Cause spongiform encephalitis such as:

  • Kuru

    • people eating people brains

  • Creutzfeldt-Jakob

Autoimmune*

Multiple Sclerosis*

• Most common de-myelinating disease of the CNS mediated by a type IV hypersensitivity reaction

  • T Cells attach of myelin so more Ts can through the BBB

  • T cells release cytokines which dilate the blood vessels

  • Now the macrophages and Bs are here

  • Plasma Bs product antibodies that target the myelin

  • Macrophages eat the oligodendrocytes leaving plaques on axons

• Etiology is unknown and the patient is typically a female aged 20-45

• Symptoms tend to wax and wane

  • You’ll see neurologic symptoms like sensory, motor, cognitive dysfunction

  • Sensory dysfunctions: loss of touch (most common), pins and needles, numbness, visual disturbance, weakness

  • Motor abnormalities: muscle weakness, tremors, spasms, ataxia, incoordination of movements, sphincter abnormalities

  • Unpredictable course

Neurodegenerative Diseases*

• Alzheimer Disease*

  • Most common cause of dementia

  • Characterized by atrophy of frontal and temporal cortex

    • Progressive loss of cognitive and functional decline

    • Loss of memory and speech issues

  • Can be familial or sporadic

  • Most common in older people (like over 70)

    • unless a brain problem has caused it and it could be earlier

  • Diagnosis of exclusion

    • you’ve gotta rule out everything else

  • Complete Pathogenesis is unclear*

    • Overproduction and decrease clearance of amyloid beta peptides forming plaques

    • Alteration in the shape of the tau protein

      • Neurofibrillary tangles

    • As brain dies, the brain atrophies with gyri getting narrow and sulci and ventricles getting bigger; atrophy leads to symptoms

• Parkinson Disease*

  • Subcortical neurodegenerative disorder characterized by movement disorders and changes in the extrapyramidal motor system

  • Unknown etiology by parksinsonism caused by pathologic event infection or drugs

  • Results from decreased number dopaminergic neurons in substantia nigra*

  • Resting Tremor

  • On gross examination, the substantia nigra appears pales due to loss of melanin-rich, dopaminergic neurons*

    • The remaining neurons are known as Lewy Bodies*

  • Degeneration of dopaminergic nigrostriatal system results in dopamine depletion in the corpus striatum

• Amyotrophic Lateral Sclerosis - ALS (Lou Gherig’s)*

  • Rare disease affects older individuals, unknown etiology

  • Characterized by motor weakness, atrophy, muscle twitching (due to lost of motor neurons)

  • Loss is most prominent in the lateral corticospinal pathways in the spinal cord

  • Slurred speech, but intellect not affected

  • Incurable, progressive disease; leads to death over

Neoplasms of CNS*

• High mortality rate

• More prominent at younger ages, can occur at any age

• 50% of tumors are primary neoplasms and can be benign/malignant

• 25% of secondary tumors are metastatic

• Cancers of the CNS DO NOT metastasize to other organs

• Most common metastatic tumors to the brain come from the lungs, breast, GI, and malignant melanoma

Classification of Neoplasms*

• Tumors of Glial Cells (75% of tumors in the CNS, all are malignant)

  • Astrocytomas: communicate with blood vessels and neurons

  • Glioblastomas: most common astrocytic tumor

  • Oligodendrocytes: CNS myelin shealth

  • Ependymomas: line brain cavities

• Tumors of neural cell precursors (2%)

  • Medulloblastoma (usually a childhood tumor)

• Tumors of the meninges (4%)

  • meningiomas - usually benign

• Tumors of the cranial and spinal (5%)

  • Neuromas: nerve sheath tumors

    • Schwannoma of CN VIII: acoustic neuromas

Bones and Joints

Metabolic

Osteoporosis

• Reduction of bone mass

• most common bone disease worldwide

• estimated that 1/3 of women over 65 have it

  • most commonly small frame

• Race, behavioral factors, and underlying bone density all have an impact on osteoporosis pathology

• Primary Osteoporosis ( type 1: postmenopausal or Type 2: senile)

  • no definitive clues

  • Majority of cases

  • No biochemical abnormalities calcium/phosphate

  • Best radiographic tool is a dual energy x-ray absorptiometry (DEXA Scan) which measures bone mineral density

    • Ranges for osteopenia: -1 to 2.5

    • Ranges for osteoporosis: below -2.5

  • Type 1 (Postmenopausal):

    • after menopause bone resorption acceleration in women 3-5X causing bone loss 1-3%

    • Vertebrae and distal radius

      • Vertebrae is common site for microfracture which may lead to wedge shaped (kyphosis) deformities making people appear shorter and bent forward

  • Type 2 (Senile)

    • typically involves cortical and trabecular bone

    • Long bones, commonly affecting femoral head

• Secondary

  • Can occur at any age

  • related to hormonal disturbances, dietary insufficiencies, immobilization, drugs (anti-seizure, blood thinners), tumors

Osteomalacia

• Inadequate mineralization of bone matrix caused by imbalance of vitamin D or phosphate metabolism

• In growing bones its called Rickets

  • type of vitamin D deficiency in children

    • Reminder: can be synthesized from light or derived from food

      • Phosphates are obtained through diet (meat and dairy)

  • Most often the growth plates are involved leading to slowed growth, and fractures of long bones

  • bowlegs

  • rachitic rosary

  • Craniotabes (softening of cranial bones)

  • Dentition delay

• Vitamin D Deficiency

  • Inadequate intake

  • lack of sun exposure

  • intestinal malabsorption

• Diagnosis is based on clinical symptoms, radiographic, laboratory findings

  • Compensatory parathyroid hyperplasia

    • low calcium/phosphate levels

    • PTH elevated

  • Osteomalacia resulting from phosphate deficiency

    • low phosphate

    • serum calcium and PTH levels are normal (feedback loop intake)

Renal Osteodystrophy

• Chronic renal failure associated with bone changes, altered homeostasis of calcium and phosphate

  • Calcium and phosphorus have an inverse relationship

• Kidneys cannot excrete phosphorus, resulting in elevated phosphate blood level, leading to hypocalcemia and compensatory hyperparathyroidism

Paget’s Disease (Osteitis Deformans)

• Chronic disease of unknown origin irregular restructuring of bone that leads to thickening and deformities

• Linked to gene locus chromosome 18

• Likely a defect of osteoclast function

• Three Phases

  1. Destructive phase: bone resorptions

  2. Mixed phase: bones resorption counterbalanced by new bone formation

  3. Osteosclerotic phase: trabecular appear irregularly thickened and the normal compact bone is replaced by wide, sclerotic, dense tissue

     • osteosarcoma may arise as a complication

• Many patients are asymptomatic or minor skeletal pain

• Common sites includes cranium, long bones of lower extremities

  • Cranial bones may compress cranial nerve and cause headaches, hearing loss, dizziness

  • Bowlegs (tib/fib)

• Diagnosis depends on honeycomb or cotton wool appearance on xray

Fractures/Deformities

• A fracture is a disruption of bone continuity

• Types of fractures: non-displaced, displaced, traumatic, compression, spontaneous

• Healing occurs with hematoma formation, granulation, callus formation, remodeling

  • Lack of calcium/phosphate, alcohol/tobacco use, lifestyle injury can complicate recovery

Compound

• Broken bone broke skin

• Tetanus shot and antibiotics even before operation

Pathological fracture

• something else causes the collapse

• The bone has been destroyed by a pathologic process (tumor, infection, cyst, osteomyletis)

Joint Dislocations

• Aka luxation

• Occurs when joint loses contact or is misaligned

• Trauma causing the dislocation may also injure surrounding structures

  • Medial epicondyle and ulnar nerve

Bacterial Infections

• Osteomylelitis: infection inside the bone

  • Most commonly the metaphysis (most vascularized area)

  • acute and chronic

  • Typically a complication bone fracture (open) or surgery

    • Chance is minimized in surgery as much as we can but chance is never zero

• Periostitis: infection of subperiosteal bone and periosteum

• Most commonly pyogenic (pus forming) cocci (usually Staph Aureus)

• Treated with surgery, IV antibiotics

• IV drug abusers have mixed flora bloodborn infections

• Sickle cell patients are predisposed to salmonella infection, which damages cells lining gut allows bacteria easier access to the bloodstream. Salmonella likes to live in the bones because there’s no oxygen

• Mycobacterium Tuberculosis is a common cause of chronic osteo of the spine (Potts disease/Hunchback deformity)

Tumors

• 50% are bone marrow based

  • multiple myeloma, leukemia

• 50% are bone forming

  • osteoma and osteosarcoma

  • Chondroma/chondrosarcoma

  • Giant Cell tumor of the bone (benign)

  • Ewing’s Sarcoma

• It is much more common that other cancers metastasize to the bones

  • These are the secondary tumors

  • Occur at a rate of 10:1

• Malignant Tumors are more common in males than females

Malignant Osteosarcoma

• Osteosarcoma is the most common primary tumor

  • More common in young adults

• Typically involves the metaphysis

• Mostly located in the knee or ankle

• Metastasize in through the blood commonly to the lung

• Treated with surgery and chemo

Malignant Chondrosarcoma

• Cartilage cells

• Originate in axial skeleton and adjacent portion of the long bones

• Graded on a scale of I to III

  • I is good

• Incidence peaks in those 35-60

• Insensitive to chemo, so surgical resection with wide margins is necessary for treatment

Ewing’s Sarcoma

• Undifferentiated bone marrow cells

• Second most common tumor of bones in kids

• May present in soft tissues as primitive neuroectodermal tumors (PNET)

  • hyperchromatic nuclei, lots of glycogen in cytoplasm, poorly understood

• Most patients (85%) have a translocation of chromosomes 11 and 22

• On X-ray you’ll see an “onion skin” (aka sunburst) due to the new bone formation of under the periosteum

  • Gotta take out the whole bone

• Occur in young people, more often in Males

• Can metastasize via the blood stream

Joint Diseases

Osteoarthritis

• Most common joint disease

• Primary osteoarthritis is when the etiology is unknown

• Secondary osteoarthritis develops under conditions that stress the joint surfaces (like trauma, etc.)

• Typically affects weight bearing joints (knee, hip, vertebral)

  • Can also affects the PIPs and DIPs, and the first MCP joint in the foot

• Increases with age

• Patients typically present with mechanical instability

  • stress and strain to the joint makes it worse

• More common in Native Americans

• In the joint you’ll see loss of cartilage, periarticular inflammation, cyst formation, osteophyte formation

• Pain can be temporarily relieved with rest

• Stiffness can improve with movement

• Other symptoms include: crepitus (grating of articular surfaces), muscle spasms

• Xrays are gonna show narrowing of joint space, sclerosis of subchondral bone, cystic bone changes, osteophytes

Pigmented Villo-nodular synovitis (PVNS)

• A type of proliferative joint disease

• unclear as too what is really going on

Rheumatoid Arthritis (RA)

• Common autoimmune disease affecting 1% of the population

• unknown etiology

• Patients are typically 40-70 y/o females

• CHRONIC joint inflammation

• Synovitis becomes exudation (inflammatory cells get into the joint)

  • stimulates the ingrowth of vessels and proliferation of synovial cells

• Exuberant synovial fronds transform into granulation tissue (pannus, cloth cover)

• Pannus is rich in inflammatory cells that secrete lytic enzymes (more inflammation)

  • These destroy cartilage and erode the underlying bone

• Patients typically have gradual onset, joint pain, swelling, redness

  • Ulnar deviation, Z deformity, swan neck, Boutonniere deformity, scleritis of the eyes, pericarditis, rheumatoid vasculitis

• Affects mostly PIPs and MCP joints of the fingers and wrist

• Labs: CCP (antibodies for cyclic citrullinated peptide) is the most specific marker

Infectious Arthritis

• Spread from bloodborne pathogens

• Viral diseases tend to cause: vague pain, transient self-limited synovitis, inflammation is usually mild and heals spontanously

• Bacterial is mostly commonly from lyme disease

Gout

• Characterized by Hyperuricemia

  • uric acid crystals are deposited in joints, kidneys, subcutaneous tissues

    • Deposits are known as Tophi if their in subcutaneous tissue

    • Deposits in the kidneys usually result in injuries ischemia/toxin/infection related injury

  • Blood uric acid levels are great than 7 mg/dl

    • extra uric acid is supposed to be secrete by the kidneys

    • Deposits form insoluble monosodium urate crystals

      • Test the synovial fluid

  • Uric acid is a result of meat metabolism

• Patients are normally male

  • Occurs in the big toe A LOT

• Symptoms are acute or chronic

  • sites are usually swollen, painful, warm

  • Fever, white count, tachy, exhaustion

  • Attack usually subsides in like 2-3 days

  • Hypertension is common and may also damage the kidneys

  • Chronic renal failure is seen in ¼ of patients with gout

• Gout predisposes patients to the formation of calcium stones

• Diagnosis based on clinical symptoms, labs proving hyperuricemia

  • Analysis of joint fluid will show WBCs and uric acid crystals

  • Xrays show bone erosion with tophi

  • Non refractive birefringent crystals

• Primary - idiopathic

  • metabolic (hyperproduction of uric acid)

    • most common

  • renal (undersecretion of uric acid)

• Secondary - due to another disease or identifiable cause

Developmental Genetic Disorders

Achondroplasia

• Inherited autosomal dominant

• Caused by a gene mutation

• Commonly affects endochrondral ossification (growth plate)

• Causes dwarfism

  • Short legs and arms and a body of relatively normal size

  • Bones of the trunk develop normally (not endochrondral ossification)

  • The calvaria and bones of the hands develop normally but the base of the head is affected

    • “saddle nose” and small jaw

Osteogenesis Imperfecta

• “defective bone formation”

• Caused by mutations involving genes encoding collagen 1 (important for the osteoid)

  • found in connective tissue so it leads to other vulnerability (skin, enamel, defective heart valves)

  • Gene defect may begin in utero, childhood, puberty, or later

• Mild forms → growth problems, recurrent fractures

• Severe forms → infant is born with numerous bone fracture

• Defective formation of the eye presents with a bluish hue to sclera

Ankylosing Spondylitis

• More common in men than women

• Patients are typically positive for the B27 HLA (MHC)

• Bamboo spine on xray

• joints in vertebral column stiffen

Misc

Circulatory Disturbances

• Aseptic bone necrosis: no bacteria, caused by ischemia

  • Legg-Calve-Perthes disease - femoral head

  • Kohler’s disease - lunate

  • Scheurmann’s disease - vertebrae

• Sickle Cell: the clumps can cause ischemia in carpal bones, femoral head/neck

Genetic Developmental Diseases

Congenital Defects

Exogenous Teratogens

• Physical teratogens: xrays, corpuscular

• Chemical teratogens: industrial chemicals, drugs, alcohol

• Microbial teratogens:

  • Virus (herpes, CMV)

  • Bacteria

  • Protozoal parasites (histoplasmosis)

Chromosome Defects ( 2% of congenital disease)

Trisomy 21 (Down Syndrome)

• Messed up meiotic division division so we get 3 21s

• Symptoms

  • Mental retardation

  • unique facial features

  • eye abnormalities

  • Gaping mouth and large tongue

    • tongue protrudes

  • Heart disease

  • Intestinal defects

  • Hand abnormalities

  • abnormalities of toes

• varying degrees of severity

• most common problem in autosomes

• Aneuploidy - change in number

Sex Chromosome (X)

• Caused by a nondisjunction of the X chromosome

• Turner’s Syndrome (XO)

  • Short stature

  • Heart-shaped face

  • Webbing of neck

  • early or long-standing heart disease

  • Broad chest

  • Cubitus valgus

  • Streak ovaries, hypoplastic uterus, amorrhea

• Klinefelter’s (XXY)

  • Tall, long arms, and legs

  • Lack of beard, body hair, pubic hair

  • Gynecomastia

  • Female-like hips

  • testicular atrophy, infertility

  • Primary hypogonadism

  • Puberty is off

• Triple XXX

  • hella rare

Mendelian Inheritance

Autosomal Dominant Inheritance

• The only group with no transmission is the recessive (rr) group

• If you have one (A) you have the disease

• Marfan’s Syndrome (Abraham Lincoln Syndrome)

  • elongated head

  • eye abnormalities

  • aortic aneurysm with dissection and exsanguination

  • lose mitral valve

  • vertebral deformity

  • long fingers (arachnodactyly)

  • High precedence of spontaneous pneumo thorax

• Achondroplastic dwarfism (SEE BONES AND JOINTS SECTION)

• Osteogenesis Imperfecta (SEE BONES AND JOINTS SECTION)

• Familial hypercholerstolemia

• Adult polycystic kidney disease

• Wilm’s tumor

• Speherocytosis

• Familial polyposis coli

• Huntington’s disease

• Neurofibromatosis

Autosomal Recessive Inheritance

• Gotta be a recessive homozygotes (aa) so you need 2 copies of the abnormal genes

• Cystic fibrosis

  • Most common autosomal recessive in US

  • White people disease (mostly like 9/10)

  • Positive sweat test

  • Exocrine glands have thick secretions due to a lack of salt (no salt, no osmosis)

  • Symptoms

    • Abnormal sweat test

    • Cor pulmonale

    • chronic pancreatitis

    • Malabsorption

    • steatorrhea

  • Patients typically die in their 20s due to pneumonia, but while alive they have issues with their intestines and pancrease

• Anemias

  • Thalessemia

  • Sickle Cell anemia

• Lipidoses

  • Tay-Sachs Disease

  • Niemann-Pick

• Mucoplysaccharidoses

  • Hunter’s syndrome

  • Hurler’s syndrome

• Amino Acid Disorders

  • Albinism

  • Phenylketonuria

    • Symptoms

      • Fair skin

      • mousy odor

      • severe mental deterioration

    • Phenylalanine is not converted to tyrosine (there’s enzyme)

    • Phenyl lactic acid is toxic to the body at high levels

    • Treatment

      • decrease phenylalanine diet

      • tyrosine supplement

X-Linked Recessive Disorders

• Heterozygous female carriers are unaffected, Males are always affected

  • Daughters of affected males are all carriers (unless the mom is also a carrier/affect)

• Duchenne-type muscular dystrophy

• Becker’s muscular dystrophy

• Wiskott-Aldrich syndrome

  • thrombocytopenia

• Agammaglobulinemia

  • impairs the maturation of Bs so there’s no humeral response

• X-linked immunodeficiency lymphoproliferative syndrome

• Hemophilia

  • Account for 90-95% of severe congenital coagulation factors

  • Classified as to mild, moderate, or severe

  • Hemophilia A

    • Hemophilia A is caused by a deficiency of clotting factor VIII

      • A = ATE (8)

    • 5X more common than B

    • 50% of cases are severe

  • Hemophilia B

    • Caused by a factor IX deficiency

    • Mild form of hemophilia B predominates

      • Clotting status can be overcome by vitamin K status

    • Christmas disease = B

• Fragile X

• Red-green color blindness

Multi-factoral Inheritance

• DM type 2

  • Based on a ton of factors like familial incidence, environmental, genetic etiology

Muscles and Peripheral Nerves

Neuromuscular Disorders (disruption of the Nerve n’ Muscle connection)

Autoimmune

• SLE, RA, and Dermatomyositis all cause inflammatory muscle lesions

• Myasthenia Gravis directly the neuromuscular junction (NMJ)

  • Causes impaired neural impulse transmission

  • More common in 20-35 y/o females

  • unknown etiology but most patients have antibodies to ACh receptors, these bind to the receptors and prevent transmission of nerve impulses (type II hypersensitivity)

  • The muscle is normal, the motor neuron plate though may have decrease invaginations (less receptor sites for Ach)

    • you might see antibodies bound to receptors under a microscope

    • Check for antibodies in the blood (most reliable diagnostic sign)

  • 75% of patients have an enlarge thymus

    • thymomas may have a pathological role

  • Symptoms: muscle weakness, fragility, may involve facial/eye muscles, ptosis, diplopia, and eye fatigue when reading, ultimately spreads to all muscles

    • Patients die from diaphragm paralysis

  • Diagnosis depends of anti-ACh test

    • inhibit the cholinesterase (the enzyme that degrades ACh)

    • flood the system with Ach

    • Symptoms temporarily improve (ACh gets to work)

  • Diagnosis can also be made with electromyographic testing

    • MG will show increase fatiguability of the muscles and respond less to electrical stimulation

  • Treatment - treat the symptoms (cholinesterase inhibitors, phasmasphersis (antibody removal) thymectomy) but its incurable

Neurogenic atrophy

• Muscle cell atrophy caused by a nerve injury

• Upper motor neuron injury

  • stroke, ALS, Trauma

• Lower Motor neuron injury

  • Polio, ischemia from DM, trauma, ankylosing spondylitis, herniated disc

• Poliomyelitis

  • A viral disease that destroys the ventral horn → paralysis

• Guillain-Barre Syndrome

  • may affect the motor neurons and cause weakness and paralysis

  • Affects peripheral nerves

  • May develop 2-4 weeks after a viral disease (postinfectious polyradiculoneuropathy)

• Traumatic injury affecting the motor neurons (like a spinal cord transection, stroke, bleeding in the brain)

  • paraplegia - paralysis of both legs

  • Hemiplegia - paralysis on one side of the body

  • Can be repaired if the proximal axon is preserved

    • the nerve distal to the transection injury degenerates with the myelin sheath

    • Wallerian degeneration means that the myelin sheath is destroyed up until the 1st node of ranvier proximal to the injury

    • Schwann cells regenerate the myelin sheath its just slow

    • Axonal growth progresses slowly but surely (1-2 cm per week)

  • Re-innervation of severed limbs/penis

    • Nerves are sutured together to allow them to regenerate

    • Remember: muscle fibers are innervated by a single axon type that determines if they are type I or II

    • Type I and Type II fibers cannot be mixed (fiber grouping)

      • In normal cases with out a crazy injury, the type I and II fibers are in a checkerboard pattern, they are not like post-fiber grouping

Congenital myopathy

• Cerebral palsy is most common form of muscle weakness and paralysis in children

  • upper motor neuron disease

  • “floppy child syndrome”

  • Muscular atrophy which is related to developmental defects of the motor cortex

    • Cause of the cerebral changes is unknown but its likely the result of a prenatal brain injury

    • Neurogenic atrophy of the muscle affects the child’s ability to move

      • typically wheel chair bound and develop secondary deformities

      • May be milder where patients can be rehabilitated with PT

Acquired Myopathy

• Nonspecific muscle weakness secondary to a identifiable cause

• Diabetic Myopathy

  • Most common acquired

  • Chronic hypo-perfusion of the muscles with blood

  • Affects the peripheral nerves causing neurogenic muscle atrophy and weakness

  • 3 Causes

    • Vascular blood flow

    • Neurogenic nerve damage

    • metabolic energy

  • Muscle biopsies are not helpful

  • small vessels have thick walls

• The thyroid and RA can also cause acquired myopathy

Muscular Dystrophies (the muscles themselves are the problem)

• Typically are inherited as mendelian traits

• Progressive in nature

• Muscle biopsies are not diagnostic

• Muscle cells degenerate and release CK (creatine kinase)

Duchenne’s Muscular Dystrophy

• Most common dystrophy

• Caused by a mutation of the dystrophin gene

  • Dystrophin normally links actin filaments to the cell membrane

    • Its the support system

• X-linked recessive disorder

  • typically males are symptomatic (1 X copy) and the females are asymptomatic carriers (Backup X)

  • 33% of the time the mother is not a carrier and there is a new mutation

• Symptoms appear in preschool boys

  • Difficulty getting up from the squatting position and must use their arms to lift the body (weakness of pelvic girdle and lower limbs)

    • literally looks like a zombie movie

  • Waddling gait at first but it becomes uncontrollable

    • Braces to walk or wheel-chair bound

  • Pulmonary involvement due to a loss respiratory muscles

    • recurrent pneumonia

    • respiratory insufficiency is the cause of death usually in the patients late teens-early twenties

• Diagnosis

  • High CK levels (degenerating muscles)

  • Muscle biopsies show deficiency of dystrophin

  • Genetic testing

Becker’s Dystrophy

• The milder but rarer form of Duchenne’s

• Occurs later in life but is progressive

  • Patients typically die from complications in 40-50s

Limb-girdle Dystrophy

• Can be inherited as a autosomal recessive or dominant traits

• Mutated genes affect the cell membrane proteins (sarcoglycans or dystroglycans) which are what dystrophin attaches to

• Presents in adulthood

• Mild-moderate muscle weakness

• Can be treated with physical therapy

Myotonic Dystrophy

• Second most common genetic muscle disease

• inherited autosomal dominant

• appears in adulthood → muscle wasting

• Caused by a DNA mutation on chromosome 19, specifically the protein kinase DMPK (dystrophia myotonica protein kinase)

• Characterized by

  • myotonia (delayed relaxtion)

    • if you hand shake them they have a hard time letting go

  • Weakness of eye muscles so eye lids droop

  • hatchet face

  • Multisystemic disease so DM, testicular atrophy, and frontal baldness are common

Mechanical Trauma

• Trauma can cause major injury and a crush injury is typically the most severe

• When muscles are damaged CK is release, lots of CK means its Rhabdo (rhabdomyolysis - rupture of muscle fibers)

• Blood vessel injury can cause intramuscular hematoma

  • when you see this on a scan, determine active or coagulative with dyes

  • This can put pressure on the nerves and even cause paralysis

• Complications

  • DIC due to proteins and myoglobin in circulation

    • Myoglobin is filtered through the kidneys (myoglonbinuria)

      • big protein damages kidneys → renal tubular necrosis → anuria

      • Dialyze immediately

• Tears and overuse injuries from excessive exercise

Myositis

• Polymyositis - more than one muscle group

Infectious

• Bacterial infections are rare

  • Ludwig’s Angina is the extension of the pharynx into neck muscles causing suppurative myositis and soft tissue gangrene

    • Common dental infections

    • We ain’t intubating if things go south, cricothyrotomy it is

  • Gas Gangrene (C. Perfringens)

    • necrosis of muscle and formation of bubbles in tissues

  • Tetanus (C. tetani)

    • infected wounds

    • Bacteria releases tetanus toxin which causes spastic contractions

      • Bacteria is gram positive

    • Lethal, get a tDAP every 5-10yrs

  • Pyogenic cocci can be bloodborne → develop intramuscular abscess

• Viral infections are most common

  • like aches and pains in the flu is viral myositis

    • muscle pain = myalgia

  • Coxsackievirus

    • viral myalgia that can affect cardiac and skeletal muscle

• The parasite Trichinella Spiralis may infect striated muscle and cause chronic localized myositis

  • Typically from uncooked pork

• Infected vegetation from heart valves can also cause an abscess

Immune Myositis

• Polymyositis - only muscles are affect

• dermatomyositis - muscles, organs and skin are affected

  • heliotropic rash of eyelids

• SLE causes myositis due to deposition of immune complexes in vessel walls

  • narrowing of arteries causes atrophy of muscle cells (typically at the periphery of fascicles)

• Sarcoidosis

  • Type IV hypersensitivity

  • noncaseating Granulomas

  • Muscles are invaded with epitheloids, giant cells, and T cells

• Polymyositis Chronic inflammation of the muscles

  • fascicles are infiltrated with T-cells and macrophages which destroy the muscle fibers

  • regeneration, hypertrophy of unaffected fibers, infra-fascicular fibrosis

• Challenging diagnosis since symptoms are non-specific (pain, weakness, difficulty moving)

• Proximal parts of the extremities are more often affected

• Systemic disease and internal organ involvement (like problems with swallowing) may be hints

• Labs

  • elevated CK (non specific just means the muscle is breaking down somewhere)

  • ANAs (antinucleated antibodies) (SLE)

  • Muscle biopsies show definitive diagnosis

• Treat with steroids and immunosuppressive drugs

Soft Tissue Tumors

• Benign

  • -omas

  • usually solitary and do not progess

• Locally invasive tumors of low malignancy

  • desmoid tumors, fibromatosus

  • locally aggressive and often reappear after surgery

  • DO NOT METASTASIZE

• Malignant

  • -Sarcomas

  • invade local tissues and metastasize normally to the lung

  • Rhabdomyosarcoma - important tumors in children

    • striated muscles (typically arms and legs)

  • Synovial sarcome

    • NOT the joint

    • highly malignant

    • arises from mesenchymal stem cells aponeurosis

    • usually in young adults

  • Liposarcoma

    • second most common tumor of adulthood

    • malignant fat cells

    • may be solid (myxoid) (high grade) or very similar to lipomas (low grade (chill))

  • Malignant peripheral sheath tumors

    • originates from peripheral nerves

    • Many develop from benign tumors

  • Polymorphous cell sarcoma (AKA MFH)

    • undifferentiated connective tissue cells and fibroblast

    • predominant soft tissue malignant tumor of adults

  • Leiomyosarcoma

    • smooth muscle

  • Angiosarcoma

    • endothelial cells

    • middle aged adults

    • head and neck

Endocrine

Pituitary

Hyperfunction

• Can occur at any of the hormone secreting cells

• Pituitary benign tumors with hyperfunction (tumor = more cells = more function)

  • Prolactinoma

    • most common

    • amenorrhea, galactorrhea, infertility in women

    • Inhibits LH and FSH

    • treat with surgery or drugs that inhibit prolactin

  • Somatotropic Adenoma

    • GH

    • Agromegaly

    • hypercalcemia, hyperglycemia

    • treat with surgery but any changes that happened to the bones won’t regress

  • Corticotropic Adenoma

    • ACTH

      • CUSHING’S DISEASE

    • treat with surgical removal

  • Gonadotropic Adenoma

  • Thyrotropic adenoma

    • extremely rare

Hypofunction

• Affect some or all (panhypopituitarism) of the hormone secreting cells

• can be congenital or acquired

  • Can occur at any age

• Pituitary dwarfism

  • Low GH

  • Congenital defect

  • Panhypopituitary in children

• Sheehan’s Syndrome AKA Acute postpartum pituitary insufficiency

  • Hypertensive episode during delivery leads to ischemia to the entire organ

  • weakness, anorexia, poor cold tolerance

• Simmonds’ disease AKA Chronic panhypopituitarism

  • Entire gland

  • Adult only

  • trigger by trauma, vascular lesions, ischemia

  • Basically identical to Sheehan’s

• Selective deficiency of trophic hormones (FSH, LH, TSH)

  • Pituitary hypogonadism

    • low FSH and LH

  • Pituitary Hypothyroidism

    • Low TSH

• Diabetes insipidus

  • lack of ADH secondary to destructive lesions

  • Most important posterior pituitary disease

  • Results in polyuria that is not osmotic

  • polydypsia

  • treated with exogenous ADH

Localized Mass Lesion

• Compression of the pituitary or optic chiasm

Thyroid

Hyperthyroidism

• Can be primary or secondary

  • Primary is a problem in the thyroid

    • Grave’s

      • Type II hypersensitivity where the antibodies bind TSH receptors triggering the production of more T3/T4

      • 85% of cases

      • 10x more common in women

    • Nodular hyperplasia

      • More cells more T3/T4

      • Treated with surgery

        • however this may induce hypothyroidism

    • adenoma

      • radioactive iodine test

    • Uncontrolled intake of thyroid hormone pills

  • Secondary is a problem in the pituitary

    • TSH is high regardless of T3/T4 levels

• In primary hyperthyroidism TSH should be low-normal because it is getting negative feedback from T3/T4

• Clinical features

  • Tachycardia, thin hair, bug eyes (exophthalmos), weight loss, diarrhea, warm skin,

Hypothyroidism

• ALWAYS primary in nature

• Developmental Disorders

  • Aplasia of the thyroid

    • Congenital

    • 1/4000 infants

• Thyroiditis (inflammation)

  • Most common type of hypothyroidism

  • Patients are typically female

  • Hashimoto’s thyroiditis (chronic autoimmune lymphocytic thyroiditis)

    • most common

    • 10x more common in females

• Thyroidectomy

  • Like if there’s a tumor, we take out the thyroid

  • Must use exogenous T3/T4

• Iodine deficiency

  • rare in Western countries due to iodized salt

  • associated with nodular goiters

• Clinical features

  • loss of hair, puffy face, bradycardia, constipation, cold intolerance, muscle weakness, edema in the extremities

  • Symptoms are non-specific so its a diagnoses of exclusion basically

Goiter

• A goiter is any enlargement of the thyroid gland

• it is a symptom and not a cause

• May be due to Grave’s, iodine deficency, or could be idiopathic

• Most are euthyroid and don’t cause hypo/hyperthyroidism

• treated with resessection

Thyroid tumors

• Benign tumors (adenomas) are much more common than malignant ones

  • Benign outnumber malignant 10:1

• Adenomas

  • Follicular adenoma is most common

  • May have cold nodules (nonfunctional thyroid tissue)

  • Diagnosis must be done with biopsy

  • Usually not treated

• Carcinomas (malignant)

  • Papillary, follicular, and anaplastic carcinoma all affect follicular cells

  • Papillary carcinoma

    • accounts for 80% of the cases

    • cold nodules

    • will metastasize in the late form

    • 4x more common in women

    • 10 year survival rate is 80%

  • Follicular carcinoma

    • 15% of cases

    • Patients are typically older that 40 and are typically women (75% of the time)

    • slow growing

    • May be cold or hot (take up radioactive iodine when tested)

      • If hot you can treat with radioactive iodine

  • Anaplastic carcinoma

    • Not a great prognosis, patients are typically dead with in a year

  • Medullary carcinoma

    • originate from C cells

    • Extra calcitonin so hypocalcium

    • no T3/T4 hormones

    • large mass in the neck typically

Parathyroid

Hyperparathyroidism

• increased gland function → increase PTH

• 18% of cases

• Primary hyperplasia

  • we just make extra PTH

  • typically its a parathyroid adenoma

  • Treated with surgery

• Secondary hyperplasia

  • the kidneys cannot reabsorb Ca2+ so we never get the feedback to get to stop making PTH

  • end-stage renal disease patients

  • A compensatory mechanism due to hypocalcemia and hyperphosphatemia

  • Vitamin D deficiency will cause the same thing

  • To treat you must correct the metabolic defect (AKA the kidneys)

• Clinical features

  • Weak bones, compensatory hypercalcemia and hypophosphatemia, calcium deposits in kidneys, KIDNEY STONES, lethargy, abdominal pain, polyuria, heart conduction defects (shorten QTc), muscle weakness

Hypoparathyroidism

• Typically results from hypofunction or complete loss of function in the parathyroid gland

• Most commonly occurs because of a surgical error, the removal of all four parathyroid glands

  • developmental and autoimmune disorders are extremely rare

• Clinical features

  • hypocalcemia

    • tetany, irregular heartbeat (prolonged QTc maybe Torsades), neurological symptoms

• Treated with exogenous PTH

Adrenal Cortex

Adrenal Hyperfunction

• Conn’s Syndrome (hyperaldosteronism)

  • hypersecretion of mineralocorticoids

  • HTN due to increased retention of Na+

• Cushing’s Syndrome (hypercortisolism) (if you see ACTH think Cushing’s disease)

  • Hypersecretion of glucocorticoids (cortisol) from adrenocortical tumors is the syndrome

    • tumors have a high lipid content

    • Endogenous Cushing syndrome

  • Most common (syndrome > disease)

  • either adrenal hyperplasia or neoplasia

  • Hypersecretion of ACTH from pituitary adenomas or a small cell carcinoma of the lung is called Cushing’s disease

  • Hypercorticsolism can be drug-induced which is the most common occurence

    • exogenous Cushing syndrome

  • Clinical features:

    • moon face, non-typical osteoporosis, buffalo hump, truncal obesity, striae of the skin, easy bruising

• Adrenogenital syndrome

  • hypersecretion of the adrenal sex steroids

Adrenal Hypofunction

• Acute adrenal insufficiency (occurs suddenly)

  • Waterhouse-Friderichsen Syndrome

    • due to menigococcal septicemia

• Chronic Adrenal insufficiency

  • Addison’s disease

    • Common causes include autoimmune dysfunctions (70%), infections, and tumors

    • Clinical features: Anorexia, nausea, hyper-pigmentation, fatigue, cardiac insufficiency, diarrhea, abdominal pain, muscle weakness

    • ACTH levels are high, cortisol and aldosterone levels are low

  • Treat with steroids and mineralocorticoids

Nonfunctioning adrenal tumors

• Neuroblastoma

  • undifferentiated precursors of neural cells that are also precursors of adrenal medullary cells

  • Adrenal gland is the most common site for neuroblastomas

  • Predominately found in neonates and peds

  • Large and fast

  • Urine may contain catecholamines or their degradation products (VMA)

  • 90% cure rate

• Pheochromocytoma

  • Most common adrenal medulla tumor in adults

    • still rare though 1/100,000

  • Causes HTN

    • HTN can be cured if you take out the tumor silly

  • Most cases are sporadic but there is some familial correlation

  • Active tumors secrete Norepi and EPI (that’s what causes the hypertension)

    • may cause lesions in the heart (catecholamine cardiomyopathy)

  • Check for Norepi and EPI in the blood and VMAs in the urine

  • Treated with surgery