Endocrine System
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Hormone classifications
o Amines: epinephrine, dopamine, T3, T4
 Hydrophilic
o Peptides (proteins, glycoproteins): insulin, glucagon, hypothalamus, pituitary hormones
o Steroid hormones – made from cholesterol: cortisol, aldosterone, testosterone
o Eicosanoids – from fatty acids: prostaglandins, leukotrienes, thromboxanes
 Hydrophobic/hydrophilic
Upregulation: limited hormone  receptor # inc  chance of connecting to hormone receptors increases
Downregulation: cell decreases receptor #  no overresponse to hormone
Functions of hypothalamus – detects state of body
o Temperature
o Blood osmolarity
o Blood nutrients
o Blood hormone levels
o Inflammatory mediators in blood
o Emotions
o Pain
5 cells of anterior pituitary gland
1) Thyrotropes: thyrotropin (thyroid stimulating hormone – TSH)
2) Corticotropes: corticotrophin (adrenocorticotropic hormone – ACTH)
3) Gonadotrophs: gonadotrophins (luteinizing hormone – LH, follicle-stimulating hormone –
FSH)
4) Somatotrophs: growth hormone – GH
5) Lactotrophs: prolactin
Categories of Endocrine disorders
o Primary: start in target gland that produces hormone
 Primary hypothyroid: thyroid gland diseased – can’t release appropriate levels of thyroid
hormone when stimulated
o Secondary: target gland normal – function altered by defective levels of stimulating
hormones/releasing factors from pituitary
 Anterior pituitary diseased – not releasing TSH that would act on thyroid to release
increased levels of hormone
 Tertiary: from hypothalamic dysfxn – both pituitary and target organ under stimulated
 Hypothalamus not functioning – no thyrotropin releasing hormone, anterior
pituitary doesn’t release TSH thyroid gland not stimulated to release thyroid
hormone
Pituitary hormones
o ACTH  stimulate adrenal cortex  cortisol
o TSH  stimulate thyroid  thyroid hormones
o GH  liver  IGF-1
o FSH/LH  gonads  sex hormones
o Prolactin  stimulates breast  milk production
Growth hormone: somatotrophin
o Linear bone growth in children
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o Stimulates cells to increase in size/grow rapidly
o Enhance amino acid transport  cell membrane
o Inc rate cells use FA
o Dec rate cells use carbs
Hypothalamus controls GH secretion
o Hypothalamus secretes
 GHRH  stim anterior pituitary  GH secretion
 Somatostatin inhibits GH secretion from anterior pituitary
o GH stimulated by
 Hypoglycemia, fasting, starvation, stress
o GH inhibited by
 Increased glucose levels, free FA release, obesity, cortisol
o GHRH released in pulsatile manner throughout day – peaks 1hr after sleep
 Regulated by negative feedback loops
GH deficiency
1) Idiopathic GH deficiency – lacks hypothalamic GHRH
2) Pituitary tumors, agenesis of pituitary – lack GH
3) Laron-type dwarfism – abnormal GH receptor
GH excess
o Before puberty = gigantism
o After puberty = acromegaly
Precocious puberty: early activation of hypothalamic-pituitary- gonadal axis
Major fxns of Thyroid Hormone
o Inc metabolism & protein synthesis
o Influence growth/development in children
Thyroid hormones – T3 and T4
o Carried by binding proteins – not biologically active
o T3 stimulates metabolism
o T4 inactive until converted into T3 in tissues using iodine
o Both use negative feedback
Hyperthyroidism (thyrotoxicosis): graves disease, thyroid tumors
o Thyroid storm
o Restlessness, irritability, anxiety, wakefulness
o Increased cardiac output
o Tachycardia, palpitations
o Diarrhea, increased appetite
o Dyspnea
o Heat intolerance, increased sweating
o Thin/silky skin & hair
o Weight loss
Graves disease: hyperthyroidism, goiter, ophthalmopathy – dermopathy less common
o Autoimmune – abnormal stim of thyroid by thyroid-stimulating antibodies
 Familial tendency
Thyroid storm
o Very high fever
o Extreme CV effects – tachycardia, congestive failure, angina
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o Severe CNS effects – agitation, restlessness, delirium
o High mortality
Hypothyroidism
o Mental/physical sluggishness
o Myxedema
o Somnolence
o Dec cardiac output, bradycardia
o Constipation, decreased appetite
o Hypoventilation
o Cold intolerance
o Coarse dry skin/hair
o Weight gain
Congenital hypothyroidism – untreated mental retardation and impaired physical growth
o Manifestations = cretinism
Thyroid insufficiency – d/t lack of iodine
o T3/T4 not made – follicular cells unable to make in thyroid gland, no negative feedback
 TRH and TSH continue to be made
Adrenal glands
o Glomerulosa: aldosterone – dec BP or inc in blood K+  prevent water and Na+ loss, causes inc
K+ elimination
o Fasciculata: cortisol
o Reticularis: sex hormone precursors
o Medulla (inner part of gland): adrenaline and noradrenaline
Cortisol function – most important glucocorticoid
o Increases
 Plasma proteins
 Catabolism
 Muscle breakdown
 Free FA
 Blood glucose
 SNS response
o Suppresses
 Immune/inflammatory systems
 Inhibits wound healing – inhibition of fibroblasts
 Increased insulin resistance – increased BG and insulin release – increased
gluconeogenesis in liver
Hypothalamus  Corticotropin releasing hormone (CRH)  anterior pituitary  ACTH  adrenal cortex
 release cortisol
Adrenal cortical disorders
o Congenital adrenal hyperplasia
o Adrenal cortical insufficiency
 Primary – Addison disease
 Usually autoimmune vs TB vs metastatic carcinoma
 S/sx
o Hyperpigmentation, hypoglycemia, hypovolemia, K+ retention,
metabolic acidosis, weakness/fatigue
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 Addisonian crisis: sudden need for aldosterone/cortisol – can’t be met
 Secondary insufficiency
 Acute adrenal crisis
o Glucocorticoid hormone excess – Cushing syndrome
 Pituitary form – Cushing disease, ectopic Cushing syndrome, iatrogenic Cushing
syndrome
 Increased cortisol in blood – HTN, inc BG  inc insulin  central obesity,
muscle/bone/skin breakdown
 Steroid meds vs pituitary adenoma (Cushing’s disease – excess ACTH excess from
pituitary gland)
Pancreas: endocrine and exocrine fxns
o Exocrine acini  digestive juices  duct  duodenum
o Endocrine islets of Langerhans  hormones  blood
Insulin
o Stimulates uptake, use, storage of glucose
 Glucose  glycogen
 Glucose  fat
 Protein synthesis
o Inhibits
 Glycogen breakdown
 Fat breakdown
 Protein breakdown
Glucagon: decreased BG and high blood amino acids  glucagon secretion
o Stimulates release of glucose into blood
 Glycogen  glucose
 Fat  fatty acids
 Protein  amino acids
Hormones affecting BG
o Catecholamines: epinephrine & norepinephrine
 Help maintain BG during stress
o GH: chronic hypersecretion  glucose intolerance  DM
 Increases protein synthesis in all cells of body
 Mobilizes fatty acids from adipose tissue
 Antagonizes effects of insulin
o Glucocorticoids: synthesized in adrenal cortex
 Critical to survival during fasting/starvation
 Stimulate gluconeogenesis by liver
o Amylin: slows glucose absorption in small intestine, suppresses glucagon secretion
o Somatostatin: decreases GI activity, suppresses glucagon and insulin secretion
o Counterregulatory hormones
 Epinephrine
 GH
 Glucocorticoids
Diabetes types
o Type 1A: autoimmune destruction of pancreatic beta cells
o Type 1B: idiopathic diabetes
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Type 2: beta cell dysfunction and insulin resistance
Other types
 Genetic defects in beta cell function
 Diabetes secondary to other disease, drugs, transplant
o Gestational DM
Prediabetes: impaired fasting plasma glucose and impaired glucose tolerance
Diabetes diagnosis: 1 of 4
o Fasting glucose greater than or equal to 126
o 2hr post-glucose load greater or equal to 200
o Hba1c greater than 6.5%
o Random plasma glucose greater than 200
Development of type 1A diabetes
o Genetic predisposition – diabetogenic genes
o Hypothetical triggering event involving environmental agent  immune response
o Immunologically mediated beta cell destruction
Idiopathic type 1B diabetes: beta cell destruction w/no evidence of autoimmunity
o Small number of type 1 – most African or Asian
o Type 1B strongly inherited
o People have episodic ketoacidosis d/t varying degrees of insulin deficiency w/periods of absolute
insulin deficiency that may come and go
Type 2 diabetes – metabolic abnormalities contributing to hyperglycemia
o Impaired beta cell fxn and insulin secretion
o Peripheral insulin resistance
o Increased hepatic glucose production
Metabolic syndrome: 3 out of 5
o Hyperglycemia
o Intra-abdominal obesity
o Increased blood TG levels
Acute complications of DM
o DKA
o HHS
o Hypoglycemia
o Somogyi affect: cycle of insulin induced post-hypoglycemic episodes  eventual resistance
 Insulin before bed  wake up with high BG
o Dawn phenomenon: increased insulin requirement between 5-9am
DKA diagnosis
o Hyperglycemia – BG >250
o Low bicarbonate – <15
o Low pH – pH <7.3
o Ketonemia – positive at 1:2 dilution
o Moderate ketonuria
Pathogenesis of DM complications
o Polyol pathway
 Glucose  sorbitol  fructose
 Increased glucose  increased sorbitol  increased osmolarity
 Microvascular damage
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Advanced glycation end products (AGEs)
 Increased glucose  glycoproteins  damage
o Protein kinase C
 Regulate vascular permeability, vasodilator release, endothelial activation, growth
factor signaling
Diabetic neuropathy
o Somatic neuropathy
 Diminished perception: vibration, pain, temperature
 Hypersensitivity: light touch, occasionally severe “burning” pain
o Autonomic neuropathy
 Defects in vasomotor and cardiac responses
 Inability to empty bladder
 Impaired mobility of GI tract
 Sexual dysfunction
Blood tests
o Fasting BG
o Casual BG
o Capillary blood tests and self-monitoring of capillary BG levels
o Glycated hemoglobin testing
Oral antidiabetic agents
o Sulfonylureas: pancreatic beta cells increase amt of insulin released
o Meglitinides: beta cells stimulate insulin release
o Biguanides: help prevent liver conversion of fats and amino acids into glucose
o Alpha-glucosidase inhibitors: slow carb digestion and absorption
o Thiazolidinediones: increase storage of FA  cells more reliant on glucose for energy
Male Reproductive Disorders
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Erection to detumescence
o Erection: parasympathetic
 Increased flow of blood into corpora cavernosa
o Emission
 Expulsion of sperm into internal urethra
o Ejaculation
 Expulsion of sperm from urethra
o Detumescence
 Penile relaxation
Balanitis: acute/chronic inflammation of the glans penis
Balanoposthitis: inflammation of glans and prepuce
o Usually males with phimosis or large, redundant prepuce that interferes with cleanliness and
predisposes to bacterial growth in accumulated secretions and smegma
o Circumcision
o Tx: corticosteroids – topical/injection
Peyronie disease: local & progressive fibrosis of unknown origin – affects tunica albuginea
o Painful erection, bent erection – presence of hard mass at site of fibrosis
o Dx w/hx and exam
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o Tx w/meds to breakdown collagen buildup or disrupt formation
Priapism: urological emergency – impaired erectile fxn if not resolved in 24-48hrs of onset
o Low-flow (ischemic) priapism: stasis of blood flow in corpora cavernosa w/resultant failure of
detumescence
 D/t decreased venous outflow
 Painful erection
 Hypercoagulable state, neuro disease, metastatic disease, meds
 Tx w/meds and surgery
o High-flow (nonischemic) priapism: persistent arterial flow into corpora cavernosa
 Penile trauma
 Non-painful erection
 Tx w/surgery
Primary priapism: problem with penis itself – trauma, infection, neoplasms
Secondary priapism
o Hematologic conditions: leukemia, sickle cell, thrombocytopenia
o Neurologic conditions: stroke, spinal cord injury, CNS lesions
o Renal failure
Complications of priapism:
o Erectile dysfunction
o Hypoxic damage – penile necrosis
Penile cancer s/sx
o Invasive carcinoma – small lump/ulcer
o Phimosis – painful swelling, purulent drainage, difficulty urinating
o Palpable lymph nodes may be present in inguinal region
Risk factors for penile cancer
o Increasing age
o Poor hygiene
 Circumcision is protective
o Smoking
o HPV
o UV radiation exposure
o Immunodeficiency states
Complications of penile cancer
o Metastasis to inguinal/fem lymph, liver, lung, bone, brain
o Penile autoamputation: spontaneous detachment of penis
Embryonic testes development/descent
o Testes develop in abdominal cavity
o Descend into scrotum through inguinal canal
o Pull blood vessels, lymphatics, nerves, ducts
o Mediated by testosterone
Maintenance of testes temperature
o Pampiniform plexus of testicular veins
 Surrounds testicular artery
 Absorbs heat from arterial blood – cools as enters testes
o Cremaster muscles
 Responds to decreases in testicular temp by moving tests closer to body
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Testicular torsion:
o Urologic emergency – lead to infertility
 Need immediate surgical de-torsion – w/in 6hrs of onset
o Can have recurrent torsion, infection, orchiectomy
o Risk factors
 Congenital failure of testes to attach to scrotum – rotate easily
 Trauma
o S/sx
 Sudden, severe pain
 Swollen, tender scrotum
 Testes move higher into scrotum
Epididymitis: inflammation of epididymis
o Types
 STIs associated w/urethritis
 Primary STI associated w/UTI and prostatitis
o Causes
 Bacterial pathogens
o S/sx
 Prince sign: elevating scrotum relieves pain
Orchitis: infection of testes
o Mostly in children d/t viral mumps infection
o Causes
 Primary infection in genitourinary tract
 Can be spread to testes through bloodstream or lymphatics
o Complications
 Atrophy
 Infertility
Testicular cancers: usually from germ cells
o Seminomas: retain phenotype
o Nonseminomas: embryonal carcinoma, teratoma, choriocarcinoma, yolk cell carcinoma
o Tumor markers: alpha-fetoprotein, human chorionic gonadotropin, lactate dehydrogenase
o S/sx
 Painless or painful mass on testes
 Lower abdominal pain
 Enlarged testes
 Dyspnea, bone pain, palpable lymph nodes – if metastasis
o Complications
 Mets to lung, liver, bone, brain
Prostate: surrounds urethra
o Enlargement causes compression
 Weak stream
 Urgency
 Dysuria
 Discharge
Types of prostatitis
o Asymptomatic inflammatory: enlarged but no other symptoms
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Acute bacterial: e. coli infection
Chronic bacterial: recurrent UTIs
Chronic prostatitis/pelvic pain syndrome
 Inflammatory/noninflammatory
Benign prostatic hyperplasia: enlargement of prostate
o Age related – older than 50
o Nonmalignant
o Nodules can compress urethra to narrow slit
o Decreasing testosterone levels can decrease prostate growth
Prostate cancer
o Risk factors
 Older than 40
 African
 Smoker
 Obese
 Family hx
 Increased animal fat diet
o S/sx
 Painful ejaculation
 Low back pain
 Hematuria
 Mets to lungs, bone
o Androgen involvement – early cancer cells need androgen to survive
o Located in peripheral zones of prostate
o Diagnosis
 Biopsy
Prostate tumor grading system
o T1: primary-state tumors asymptomatic – discovered on histologic exam of prostatic tissue
specimens
o T2: tumors palpable on digital exam but confined to prostate gland
o T3: tumors extended beyond prostate
o T4: tumors pushed beyond prostate to involve adjacent structures
Hypospadias: ventral
o Congenital abnormal urethral opening
o Most common
Epispadias: dorsal
o Congenital abnormal urethral opening
Phimosis: tightening of prepuce of penile foreskin that prevents retraction over glans
Paraphimosis: foreskin so tight and constricted it cannot cover glans
Cryptorchidism: incomplete/partial descent of testes into scrotal sac
o Most cases resolve spontaneously during 1st year of life
Effect of aging on male reproductive system
o Degenerative changes occur – less efficient w/age
o Declining physiologic efficiency of male reproductive function occurs gradually
 Involves endocrine, circulatory, neuromuscular systems
Female Reproductive Disorders
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Menstrual cycle
o GnRH from hypothalamus begins cycle
 Stimulates anterior pituitary to release FSH and LH
 FSH stimulates development of follicle cell layers
o Follicular phase of menstrual cycle
o Developing follicle produces estrogen
 Estrogen decreases FSH release, LH increases
 Estrogen stimulates LH release from anterior pituitary
o LH stimulates mature follicle to burst  release of egg = ovulation
 Follicle cells become corpus luteum – produce progesterone
o Luteal phase of menstrual cycle
 Progesterone prepares body for pregnancy
o No pregnancy  corpus luteum replaced by corpus albicans
o Drop in progesterone tells hypothalamus to secrete GnRH and begin
new cycle
Estrogens: protective factor for women
o Sexual maturation, skeletal growth, fat distribution
o Ovulation, implantation, pregnancy, parturition
o Development, maintenance of female accessory organs
o Cell division in breasts and endometrium
o Maintain skin/bone vessels
o Decrease bone resorption
o Increase HDL, triglycerides; decrease LDL, cholesterol
o Sodium and water retention
Progesterone
o Maintain pregnancy – create mucus plug
o Breast and endometrium development
o Increase body temp
o Smooth muscle relaxation
Phases of endometrial cycle
o Proliferative/preovulatory phase
 Glands and stroma of superficial layer grow rapidly under influence of estrogen
o Secretory/postovulatory phase
 Progesterone produces glandular dilation and active mucus secretion
 Endometrium becomes highly vascular and edematous
o Menstrual phase
 Superficial layer degenerates and sloughs off
Composition of cervix
o Exocervix – visible portion: stratified squamous epithelium, also lines vagina
o Endocervical canal: columnar epithelium
Cervical cancer as STD
o Evidence of link b/w HPV and cervical cancer
o Risk factors
 Early age of first intercourse
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 Smoking
 Multiple sexual partners
 Prolonged time on contraceptives
 History of STDs
 Promiscuous male partners
o Associated w/HPV types 16, 18, 31, 33, 45
o Gardasil: prevent infection w/16, 18, 6, 11
 Two strains of HPV (16 and 11) responsible for 70% of cervical cancers
 Two most common benign strains (6 and 11) account for up to 90% of genetal warts
o Main complications: mets to lung, liver, bone
o S/sx:
 Early stages: asymptomatic
 Heavy/irregular bleeding
 Low back pain
 Watery, mucus, purulent vaginal discharge
Diagnosis
o Pap smear demonstrating squamous intraepithelial lesion
o Colposcopy
o Biopsy
o Cervicography
o LEEP or LLETZ
Early tx of cervical cancer
o Removal of lesion
 Biopsy or local cautery
 Electrocautery, cryosurgery, carbon dioxide laser therapy – used to tx moderate to
severe dysplasia limited to exocervix
 Therapeutic conization if lesion extends into endocervical canal
Endometriosis: endometrial tissue outside uterus
o Retrograde menstruation: blood flow back into body
o Metastasis through lymphatics or vascular system
o Activation of dormant cells that were always there
o Risk factors
 No children
 Long estrogen exposure – prolonged menarche, late menopause
 Low BMI
 Increased dietary trans-fat diet
 Menstrual flow obstruction
o Side effects: infertility and pain
o Ectopic implants respond to hormones
 Go through menstrual cycle
 During menstrual period – tissue dies and bleeds
 Pain and adhesions result
Endometrial cancer
o Adenocarcinoma: starts in mucus producing glandular cells
o Types
 Prolonged estrogen stimulation and endometrial hyperplasia
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 Hyperestrinism and endometrial hyperplasia
o Hormone sensitive, low grade, favorable prognosis
o Painless bleeding
Cystocele: herniation of bladder into vagina
Rectocele: herniation of rectum into vagina
Uterine prolapse: bulging of uterus falling into vagina
Enterocele: small intestine into pelvic cavity
Polycystic ovary syndrome: chronic anovulation  amenorrhea or irregular menses
o Cause bilateral ovarian enlargement
o LH > FSH
 Stimulates androgen production
 Interferes with ovulation
 Ovaries contain many unovulated follicles
o S/sx
 Acne, hirsutism
o Complications
 Infertility
 Increased insulin resistance
o Tx: symptom relief, decrease malignancy
Ovarian cancer
o Ovulatory age – most significant risk factor
 BRCA1/BRCA2 increase susceptibility
 High-fat diet/genital talc powders linked
o S/sx: vague GI symptoms
 Abdominal distention, bowel obstruction, abdominal/pelvic pain
o No good screening tests
o Tx: surgery
Menopause/climacteric
o Decreased ovary function
 No menstrual cycle for 1 full year
 Peri-menopause: 4 years prior to menopause – missed and irregular cycles
o Low estrogen and progesterone  decreased hypothalamic inhibition  increased GnRH 
increased FSH and LH from anterior pituitary
 Causes hot flashes
 Vulvovaginal atrophy – dryness, loss of rugae
 Increased CV disease risk
 Atherosclerosis risk
 Decreased bone density, lean body mass, collage, cognitive fxn
 Osteoporosis risk
 Mood instability
Breast cancer – ductile, lobule, inflammatory carcinomas
o Risk factors
 Sex, age
 Hx of breast cancer or benign breast disease
 Hormonal influences
 Obesity
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 Long-term use of postmenopausal hormone therapy
 Alcohol
 Physical inactivity
Exam: mammography, self-exam
Known mutations
 BRCA1: chromosome 17 – tumor suppressor
 BRCA2: chromosome 13
Diagnosis
 Physical exam
 Mammography
 Ultrasonography
 Percutaneous needle aspiration
 Stereotactic needle biopsy
 Excisional biopsy
S/sx
 Mass
 Skin dimples
 Discharge
Complications – mets – bone, lung, liver, brain
STIs
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External infections
o Condylomata acuminate (genital warts): HPV
 Cancer @ wart site
 Prevent w/pap smear and condoms
o Herpes
 S/sx: discharge, blister, ulcer, pain
o Chancroid
 S/sx: sores around genitals
o Granuloma
 S/sx: thick, red, puffy sores
Vaginal infections
o Candidiasis: yeast
 S/sx: itchy discharge
 Risk: DM, immunosuppressants, antibiotics, contraceptives, pregnancy
o Trichomoniasis: parasite
 S/sx: discharge, burning, itching
o Bacterial vaginosis: overgrowth of natural bacteria
 Risk: increased risk w/HIV & STDs, premature birth, low birth weight
 S/sx: discharge (fish), itching, burning
Urogenital – systemic infections
o Chlamydia: bacteria
 Risks: increased number of sexual partners, impaired mucous membranes
 S/sx: asymptomatic, painful urination, pain w/sex discharge
 Tx: antibiotics
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Gonorrhea: gram negative diplococcus
 Usually from unprotected sex
 Can lead to PID and infertility
 S/sx: asymptomatic, painful urination/sex, rectal fullness/discharge/bleeding, vaginal
itching/draining
 Tx: intramuscular injection
Syphilis: bacterial
 Localized or systemic
 Sexual or perinatal transmission
 Risks: unprotected sex, increased sexual partners, male sex
 S/sx: painless sore on genitals, rectum, mouth  body rash
 Complications: neurosyphilis, ocular syphilis (blindness)
 Tx: antibiotics
Musculoskeletal and Integumentary System
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Functions of bone
o Protects/maintains position of soft tissue
o Framework provides stability for body
o Maintains body’s shape
o Bones = storage reservoir for calcium
o Contain hematopoietic connective tissue responsible for formation of blood cells
o Protect organs and provide rigid support for extremities
o Cartilage provides cushioning/flexibility for bones and in pre/postnatal skeletal development
Composition of intracellular matrix of bone
o Organic matter
 Bone cells, blood vessels, nerves, inorganic salts
o Inorganic salts
 Calcium phosphate slats, small amounts of calcium carbonate, calcium fluoride
Two types of bone
o Compact bone – cortical
 Outer shell and diaphysis of long bones
 Comprised of densely packed calcified intercellular matrix – more rigid than cancellous
bone
o Cancellous bone – spongy
 Interior of bones
 Composed of trabeculae and spicules
 Lattice structures lined w/osteogenic cells and filled with red and yellow bone marrow
Long bone: composed of shaft (diaphysis) and epiphysis (two ends)
o Metaphysis: trabeculae and cores of cartilage
o After puberty – epiphyses and metaphysis merge  growth plate eliminated
Bone cells
o Osteoprogenitor cells: undifferentiated cells  differentiate into osteoblast
 In periosteum, endosteum, epiphyseal plate of growing bone
o Osteoblasts: bone building cells
 Form bone matrix
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Synthesize collagen and protein for osteoid tissue, participate in calcification
Secreted growth and tumor necrosis factors
Secrete alkaline phosphate (enzyme) to raise calcium and phosphate levels to point of
precipitation occurs
o Osteocytes: mature bone
 Maintains matrix
o Osteoclasts: bone chewing cells
 Large phagocytic cells
 Resorb bone, remove mineral content
 Parathyroid hormone  increases osteoclasts
 Increases blood calcium levels
 Calcitonin and estrogen  decrease osteoclasts
 Decreases blood calcium levels
Bone growth/remodeling
o Normal growth: as bones grow in length – cartilage cells in deeper layers of growth plate
multiply, enlarge, calcify
o Children: separation of epiphyseal growth plate results in rupture of blood vessels that nourish
epiphyses
 Leads to cessation of growth and shortened extremity length
o Growth plate sensitive to metabolic/nutritional changes
 Vitamin D deficiency/alteration in thyroid hormone, insulin like growth factor and
insulin effect growth
o Alterations during growth periods
 Torsional deformities, genu varum (bowlegs), genu valgum (knock-knees)
Hereditary/congenital deformities
o Osteogenesis imperfecta: defective synthesis of type 1 collagen
 4 major subtypes
o Developmental dysplasia of hip
 More females and on LEFT
o Congenital clubfoot
 Boys more prone – need casting to fix
Cartilage: connective tissue – firm yet flexible
o Fibers embedded in amorphous, gel-like material
o Types
 Elastic: contains intracellular elastin – ear
 Hyaline: pure cartilage – pearly white
 Fibrocartilage: intervertebral disks, symphysis pubis
Hormonal control of bone formation – PTH, calcitonin, vitamin D
o PTH: increases blood calcium levels
 Cause more bone degradation  calcium released into blood
 Kidneys resorb more calcium (versus being urinated out), GI tract resorb more calcium
o Calcitonin: secreted by parafollicular cells of thyroid
 Acts on bone, kidneys, GI to decrease blood calcium
o Vitamin D: fat-soluble hormone
 Needs to be activated to help retain more calcium – via intestines or UV light
Tendons: attaches muscles to bone
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o Inextensible secondary to collagen fibers
o Enveloped by loose connective tissue blood vessels and nerves
Ligaments: attach bone to bone
o Do not stretch – they tear
Both tendons & ligaments can become inflamed and torn
Bursae: closed sacs – contain synovial fluid and not part of the joint
o Prevent friction on tendon
o May be injured or inflamed – pain, discomfort, swelling, limited movement
Menisci: fibrocartilage structure in some synovial joints  creates pad between articulating bones
o Menisci of knee joint may be torn as result of injury
Soft tissue injuries – muscles/tendons/ligaments
o Contusion: direct injury/trauma to soft tissue
 Caused by striking body part against hard object
 Ecchymosis
o Hematoma: local hemorrhage
 Blood accumulates in tissue and puts pressure on nerves – pain, swelling, infection
o Laceration: skin torn/disrupted  open wound
 Tx: depends on length, width, depth, exposure of tendons/bone
Joint injuries
o STrain: stretching injury to muscle/Tendon
o Sprain: injury to ligament
o Dislocation: displacement/separation of bone – ends w/loss of articulation
o Subluxation: partial dislocation
o Loose bodies: small pieces of bone/cartilage within joint space
Rotator cuff injury: acromioclavicular + glenohumeral
o S/sx:
 Pain/impingement w/movement secondary to squeezes tissue between humorous and
arch
o Diagnosis
 H&P including specific shoulder exam maneuvers
 X-ray, arthrography, CT, MRI, shoulder US, arthroscopic exam for dx, arthroscopy for tx
o Tx
 Rest, pain management (NSAIDS), corticosteroid injections, PT/rehab, exercise, activity
limitations, surgery (arthroscopy)
Knee injuries
o Meniscus injuries: often d/t rotation injury
o Patellar subluxation/dislocation
 D/t trauma, sports injury, physical activity, congenital disorders
o Chondromalacia
 Articular cartilage degeneration – common under patella
 Etiology: recurrent subluxation/overuse
Hip injury
o Dislocation: emergency disruption of blood supply to femoral head  avascular necrosis
o Fracture: classified according to anatomic part
 Location important secondary to blood supply
Bone/fracture healing
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Hematoma formation: 2-3 days
 Blood clot stops vessels from bleeding
 Clotting factors and resorption of hematoma
o Fibrocartilaginous callous formation: 2-3 wks
 New blood vessels bring oxygen and nutrients
 Soft callus bridge b/w sides
 Made by fibroblasts
 Non-weight bearing
o Bony callus formation: 4wks – months
 Osteoblasts replace soft callus with bone
o Remodeling: undergoing all the time
Fractures
o Diagnosis
 H&P
 X-ray
 Determine fracture type, severity
 Identify involvement of muscles
 Tendons and ligaments
 Soft tissue injury
 Deep skin abrasions, muscle contusions
o Fracture blisters, massive soft tissue swelling
o Treatment
 1) Reduce (& internal fixation): realign bone
 2) Immobilize (& external fixation)
 3) Restore function
 Healing complications
 Delayed union
 Malunion: deformity
 Nonunion: not healing
 Osteonecrosis
 Loss of skeletal continuity
 Bone fragment injury
o Brain injury or pneumothorax
 Swelling/hemorrhage
o Fracture blisters, compartment syndrome
 Nerve fibers injury/involvement
o Reflex sympathetic dystrophy and causalgia, numbness, tingling
 Development of fat emboli: long bones w/lots of yellow marrow
o Petechiae, SOB  tx by reversing hypoxia and w/steroids
 Pain
 Thromboemboli
Bone infections – osteomyelitis: acute or chronic infection
Benign neoplasms
o 1) osteoma: small bony tumor on surface of long bone, flat bone, or skull
o 2) chondroma: composed of hyaline cartilage
 Common in hands/feet
3) osteochondroma (cartilage and bone): forms in epiphyseal cartilage during periods of skeletal
growth
 Tumors grow out of bone
o 4) giant cell tumor (osteoclastoma): aggressive, multinucleated cells – metastasize through blood
stream and recur after excision
 Results in bone destruction
 Pathologic fractures common
 Categorized as benign  can become malignant
Malignant bone tumors: secondary bone tumors more common than primary
o Osteosarcoma: at joints
 Common in kids & areas of growth
o Ewing sarcoma: younger age
 Common in femur
o Chondrosarcoma: takes up bone and cartilage – middle-late life
Scoliosis: lateral deviation of spinal column – may/may not include rotation/deformity of vertebra
o Usually painless, respiratory problems, rib/back pain
o Idiopathic scoliosis – infantile/juvenile
 Structure spinal curvature w/unknown cause
o Congenital scoliosis: disruption in vertebral development in 6-8th week of embryologic
development
 Missing part of vertebra/failure of segmentation
o Neuromuscular scoliosis: secondary to neuropathic/myopathic disease
 CP, muscular dystrophy, myelodysplasia, poliomyelitis
Osteopenia: reduction in bone mass greater than expected for age, race, sex d/t decrease in bone
formation, inadequate bone mineralization, excessive bone deossification
Osteoporosis: loss of mineralized bone mass  increased porosity of skeleton and susceptibility to
fractures
o Most at risk: increasing age, females, petite frame, white/Asian, excessive caffeine/alcohol,
decreased weight bearing exercise, transition into menopause  higher risk
Osteomalacia & rickets: both produce softening of bones
o Osteomalacia: inadequate mineralization of bone d/t calcium or phosphate deficiency or both –
Adults
o Rickets: failure/delay in cartilaginous growth plate calcification – KIDS
 Etiology: inadequate sun exposure, vitamin D, calcium, phosphorus intake
 Chronic disease
 Genetics
Paget Disease: excessive bone destruction and repair
o Lesions have intense cellular activity, increased vascularity, bone marrow fibrosis
o Etiology: unclear, genetics, paramyxovirus, environmental factors
Rheumatoid arthritis: autoimmune – triggered by trauma, virus
o T- mediated response – rheumatoid factor
o Associated w/extra-articular and articular manifestations
o Insidious onset – systemic manifestations: fatigue, anorexia, weight loss, generalized
aching/stiffness
o Exacerbations/remissions
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 Only few joints for brief duration or relentlessly progressive and debilitating
Criteria for RA
 Morning stiffness at least 1hr for at least 6 wks
 Swelling of 3 or more joints at least 6 wks
 Swelling of wrist, metacarpophalangeal, proximal interphalangeal joints for 6 or more
wks
 Systemic hand swelling
 Hand roentgenogram changes typical of RA
 Rheumatoid nodules
 Serum rheumatoid factor
o Clinical manifestations
 Fingers
 Hyperflexion: proximal – swan neck deformity
 Flexion = distal
 Ulnar deviation
o Treatment for RA
 Reduce pain
 Minimalize stiffness/swelling
 Maintain mobility
 Informed healthcare consumer
Systemic Lupus Erythematosus (SLE): formation of antibodies/immune complexes
o B-cell hyperreactivity
 Increased production of antibodies against self and nonself antigens
 Autoantibodies can directly damage tissues/combine w/corresponding antigens to form
tissue-damaging immune complexes
o 90% have arthritis type S/sx
Systemic sclerosis: autoimmune disease of connective tissue characterized by excessive collagen
deposition in skin and internal organs
o More common in females vs males, age 25-50
o Diffuse or generalized form: skin changes in trunk and proximal extremities
o Limited or CREST variant: hardening of skin (scleroderma) limited to hands and face
Manifestations of ABCD-CREST syndrome: need 4 for diagnosis
o A: antibodies to CENP, anti-tropo1 or fibrillarin
o B: bibasilar pulmonary fibrosis
o C: contractures of digital joints
o D: dermal thickening proximal to wrists
o C: calcinosis – calcium deposits in subcutaneous tissue  erupt through skin
o R: Raynaud syndrome
o E: esophageal dysmobility
o S: sclerodactyly – localized scleroderma of fingers
o T: telangiectasia
Ankylosing spondylitis
o More common in males vs females, young teens
o Fusion of skeletal joints  decrease ROM & flexion
o Tx: pain control, inflammation, increase mobility
Psoriatic arthritis: T-cell mediated, similar to RA
o
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o Oligoarticular/asymmetric: often mild
o Spondylitis: pain, stiff in spine and neck
o Polyarticular/symmetric
o Distal interphalangeal: ends of fingers
o Mutilans: most severe
Osteoarthritis: degenerative joint disease – wear and tear arthritis
o Primary variants of OA – localized or generalized syndromes
o Usually isolated to bone vs autoimmune sx
o Secondary OA has known underlying cause
 Congenital/acquired defects of joint structures, trauma, metabolic disorders,
inflammatory diseases
Gout syndrome: acute gouty arthritis w/recurrent attacks of severe articular/periarticular inflammation
o More common in males than females, age 40-50
o Tophi or accumulation of crystalline deposits in articular surfaces, bones, soft tissue, cartilage
o Gouty nephropathy/renal impairment
o Uric acid kidney stones
o Tx: decrease cyclical gout attacks, decrease purine in diet
 Correct hyperuricemia
 Inhibit further precipitation of sodium urate
 Absorption of urate crystal deposits already in tissues
Juvenile idiopathic arthritis
o 1) systemic onset disease: fever, rash, joint pain, anemia
o 2) oligoarticular arthritis: multiple joints
o 3) polyarticular disease: 5 or more joints
o S/sx: synovitis, stunted growth, influence epiphyseal growth by stimulating growth of affected
Layers of skin
o Outer epidermis: avascular layer w/4-5 layers of stratified squamous keratinized epithelial cells –
formed in deepest layer of epidermis
 Cells migrate to skin surface to replace cells lost during normal shedding
o Basement membrane: thin adhesive layer cementing epidermis to dermis
 Involved in blister formation
o Inner dermis: connective tissue layer separating epidermis from underlying subcutaneous fat
layer
 Contains blood vessels and nerve fibers that supply epidermis
Cells of epidermis
o Keratinocytes
o Melanocytes
o Merkel cells: sensory info
o Langerhans cells: immune cells – link epidermis and immune system
Immune cells in dermis
o Macrophages: dermis
o T-cells: dermis
o Mast cells: stay in tissue area  histamine
o Fibroblasts
Puritis/itching
o Originate in free nerve endings in skin  carried by small myelinated type C nerve fibers
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o Itch & pain are antagonistic
o Caused by: histamine, tryptase, opioids, neuropeptides, substance P, bile salts, bradykinin
Xerosis: dry skin – dehydration of stratum corneum
Pigmentary skin disorders
o Melanocytes: absence of melanin production
 Vitiligo: patches
 Albinism
o Increase in melanin
 Mongolian spots: pigment trapped
 Melasma: darkened facial area – pregnancy, contraception, sun exposure
Fungal infection: superficial
o Tinea, candida
Bacterial infections
o Primary infections: superficial
 Impetigo: small vesicle/pustule or large bulla on face/elseware
 Ecthyma: ulcerative form of impetigo
o Secondary infections: deep cutaneous infections
 Infected ulcer
 Cellulitis – portal of entry into skin
Viral infections: use host cells to replicate
o Human papillomavirus: verrucae (warts) common benign papillomas
o Herpes simplex virus
 Type 1: spread by respiratory droplets/direct contact w/infected saliva – oral herpes
 Type 2: genital herpes
o Herpes zoster/shingles: localized vesicular eruptions distributed over dermatomal segment of
skin
 Dermatome affecting eye = medical emergency  severe post herpetic neuralgia
Acne
o Noninflammatory: comedones
 Plugs of material that accumulate in sebaceous glands opening to skin surface
o Inflammatory: papules, pustules, nodules, cysts
 Escape of sebum into dermis and irritating effects of fatty acids contained in sebum
o Types
 Acne vulgaris: chronic inflammatory disease of pilosebaceous unit
 Acne conglobate: comedones/cysts have multiple openings, large abscesses,
interconnecting sinuses
 Discharge: odoriferous, serous, mucoid, purulent
 Affected persons have anemia w/elevated WBC, sedimentation rates,
neutrophil counts
Rosacea: chronic inflammatory process accompanied by vascular instability w/leakage of fluid and
inflammatory mediators into dermis
o Accompanied by GI symptoms
o Types
 Erythematotelangiectatic: butterfly rash
 Papulopustular
 Ocular
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 Phymatous: more males than females, thickened nodules, enlarged nose, rhinotyma
Allergic/hypersensitivity dermatoses
o Contact dermatitis:
 Allergic contact dermatitis: cell-mediated, type IV hypersensitivity response
 Delayed T-cell response
 Irritant contact dermatitis caused by chemicals that irritate skin
o Atopic dermatitis: eczema
 Inflammatory skin disorder – poorly defined erythema, edema, vesicles, weeping at
acute stage
o Nummular eczema
 Coin-shaped papulovesicular patches involving arms/legs
Drug-induced skin eruptions
o Bullous skin lesions
 Erythema multiforme minor
 Stevens-Johnson syndrome: major systemic ulcers/detachment – less than 10% of body
 Toxic epidermal necrolysis: skin detachment on 30% or more of body
Cirrhosis: abnormal growth of keratinocytes, dermal blood vessels, thickening epidermal layer
o T-cells overactive
o Characterized by plaques
Lichen planus: autoimmune – epithelial cells attacked
o Small, irregular papules all over body
o Stop new meds, topical corticosteroids, antipyretic
Arthropod infestations
o Scabies: itchy, inflammatory
o Pediculosis: lice
o Ticks
 Rocky mountain spotted fever: abdominal rash, vomiting, headache
 Lyme disease: heart block, neuro changes, bullseye rash
Degrees of burns:
o 1st degree: superficial partial-thickness – only outer layers of epidermis
 Pain, no blister, red/pink, dry
nd
o 2 degree: partial-thickness – epidermis and various degrees of dermis
 Pain, moist, red, blister (basement membrane)
rd
o 3 degree: full-thickness – entire epidermis and dermis
 Pain, red/pink waxy look, some blister
th
o 4 degree: full-thickness – extend into subcutaneous tissue and may involve muscle/bone
 Dry, leather/black/brown, less pain (nerves destroyed), skin grafts
Systemic burn complications: magnitude proportional to extent of injury
o Hemodynamic instability  major organ dysfunction
 Hypovolemic shock  evaporation of water b/c loss of skin
o Impaired respiratory function: swelling, vasodilation, increased capillary permeability
o Hypermetabolic response
o Sepsis  loss of protective covering
Treatment of burns
o Immediately submerge into cool-lukewarm water
o Emergency care
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 Resuscitation
 Stabilization
 Maintain cardiac/respiratory function
o Intermediate/long-term treatment dependent on extent of injury
 Projection from desiccation
 Escharotomy/fasciotomy
Pressure ulcers: ischemic lesions of skin/underlying structures caused by unrelieved pressure – impair
blood/lymph flow
o 4 factors contribute to development
 Pressure
 Shear forces
 Friction
 Moisture
o Prevention
 ID risk groups
 Maintain/improve tissue tolerance to prevent injury
 Protect against adverse effects of extremal mechanical forces
 Reduce incidence of pressure ulcers through education
o Risk factors
 Increased moisture/incontinence
 Sedentary lifestyle
 Decreased mobility
 Poor-nutrition
3 major types of skin cancers
o Malignant melanoma: rapidly progressing malignant tumor of melanocytes – UV exposure
o Basal cell carcinoma: neoplasm of nonkeratinizing cells of basal layer of epidermis
 Most common skin cancer in white skinned people
o Squamous cell carcinoma
 Second most frequently occuring malignant tumors of outer epidermis
o Risk factors: blonde/red hair, freckles, sunburns early, moles, family history,
immunocompromised
ABCDs of skin cancer
o A: asymmetrical
o B: border irregularity
o C: color variation
o D: >6mm diameter – pencil eraser
o E: evolve quickly
Skin manifestations/disorders in elderly
o Normal aging
 Diminution in subcutaneous tissue
 Thinning of epidermal/dermal layers
 Decrease in number of melanocytes, Langerhans cells, Merkle cells
 Decrease and thickening of blood vessels
o Skin lesions common
 Skin tags
 Keratoses
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Lentigines
Vascular legions