First_Aid_for_the_USMLE_Step_1_2023_Compressed_-451-849

["480 SECTION III Musculoskeletal, Skin, and Connec tive Tissue\u2003 \uf07d\u2009Pathology Neuromuscular junction diseases Myasthenia gravis Lambert-Eaton myasthenic syndrome Uncommon FREQUENCY Most common NMJ disorder Autoantibodies to presynaptic Ca2+ channel PATHOPHYSIOLOGY Autoantibodies to postsynaptic ACh receptor \u008e\u00a0\u0090\u00a0ACh release; L comes before M CLINICAL Fatigable muscle weakness\u2014ptosis; diplopia; Proximal muscle weakness, autonomic proximal weakness; respiratory muscle symptoms (dry mouth, constipation, ASSOCIATED WITH involvement \u008e\u00a0dyspnea; bulbar muscle impotence) AChE INHIBITOR ADMINISTRATION involvement \u008e\u00a0dysphagia, difficulty chewing Hyporeflexia Spared reflexes Improves with muscle use Worsens with muscle use Small cell lung cancer Minimal effect Thymoma, thymic hyperplasia Reverses symptoms (pyridostigmine for treatment) Ca2+ channel Antibodies to Ca2+ Ca2+ channel ACh Antibodies to ACh receptor ACh receptor Myasthenia gravis Lambert-Eaton myasthenic syndrome Raynaud phenomenon \u0090 blood flow to skin due to arteriolar (small vessel) vasospasm in response to cold or stress: A color change from white (ischemia) to blue (hypoxia) to red (reperfusion). Most often in the fingers A and toes. Called Raynaud disease when 1\u00b0 (idiopathic), Raynaud syndrome when 2\u00b0 to a disease process such as mixed connective tissue disease, SLE, or CREST syndrome (limited form of systemic sclerosis). Digital ulceration (critical ischemia) seen in 2\u00b0 Raynaud syndrome. Treat with calcium channel blockers.","Musculoskeletal, Skin, and Connec tive Tissue\u2003 \uf07d\u2009Dermatology SECTION III 481 Scleroderma Systemic sclerosis. Triad of autoimmunity, noninflammatory vasculopathy, and collagen deposition with fibrosis. Commonly sclerosis of skin, manifesting as puffy, taut skin A without wrinkles, fingertip pitting B . Can involve other systems, eg, renal (scleroderma renal crisis; treat with ACE inhibitors), pulmonary (interstitial fibrosis, pulmonary HTN), GI (\u0090 peristalsis and LES tone \u008e dysphagia, heartburn), cardiovascular. 75% female. 2\u00a0major types: \u0083\t Diffuse scleroderma\u2014widespread skin involvement, rapid progression, early visceral involvement. Associated with anti-Scl-70 antibody (anti-DNA topoisomerase-I antibody) and anti-RNA polymerase III. \u0083\t Limited scleroderma\u2014limited skin involvement confined to fingers and face. Also with CREST syndrome: Calcinosis cutis C , anti-Centromere antibody, Raynaud phenomenon, Esophageal dysmotility, Sclerodactyly, and Telangiectasia. More benign clinical course. ABC `\u2009MUSCULOSKELETAL, SKIN, AND CONNECTIVE TISSUE\u2014DERMATOLOGY Skin layers Skin has 3 layers: epidermis, dermis, subcutaneous fat (hypodermis, subcutis). Epidermal layers: come, let\u2019s get sunburned. A Stratum corneum Stratum lucidum Stratum granulosum Stratum spinosum Stratum basale Dermis uploaded by medbooksvn","482 SECTION III Musculoskeletal, Skin, and Connec tive Tissue\u2003 \uf07d\u2009Dermatology Epithelial cell junctions A Claudin\/ Tight junctions (zonula occludens) A \u2013prevents B occludin paracellular movement of solutes; composed of Apical claudins and occludins. Tight junction Adherens junction (belt desmosome, zonula Adherens junction Cadherins adherens) B \u2013forms \u201cbelt\u201d connecting actin cytoskeletons of adjacent cells with cadherins C (Ca2+-dependent adhesion proteins). Loss of E-cadherin promotes metastasis. Intermediate \ufb01laments Desmosome (spot desmosome, macula adherens) C \u2013structural support via intermediate filament Desmosome interactions. Autoantibodies to desmoglein 3\u00a0+\/\u2013 desmoglein 1 \u008e\u00a0pemphigus vulgaris. D Connexon Gap junction D \u2013 channel proteins called 100 nm Gap junction connexons permit electrical and chemical communication between cells. Basal E Hemidesmosome E \u2013 connects keratin in basal Hemidesmosome Integrin cells to underlying basement membrane. Autoantibodies \u008e\u00a0bullous pemphigoid. Fibronectin\/ (Hemidesmosomes are down \u201cbullow.\u201d) laminin Integrins\u2013membrane proteins that maintain ECM\/collagen integrity of basolateral membrane by binding to collagen, laminin, and fibronectin in basement membrane. Exocrine glands Glands that produce substances other than hormones (vs endocrine glands, which secrete hormones) that are released through ducts to the exterior of the body. Can be merocrine (eg, salivary and sweat glands), apocrine (eg, mammary glands), or holocrine (eg, sebaceous glands). Secretory Pinched Disintegrating vesicle portion of cell cell Merocrine Apocrine Holocrine secretion secretion secretion","Musculoskeletal, Skin, and Connec tive Tissue\u2003 \uf07d\u2009Dermatology SECTION III 483 Dermatologic macroscopic terms LESION CHARACTERISTICS EXAMPLES Macule Flat lesion with well-circumscribed change in Freckle (ephelis), labial macule A skin color < 1 cm Patch Vitiligo B Papule Macule > 1 cm Neurofibroma C , acne Plaque Elevated solid skin lesion < 1 cm Psoriasis D Vesicle Papule > 1 cm Chickenpox (varicella), shingles (zoster) E Bulla Small fluid-containing blister < 1 cm Bullous pemphigoid F Pustule Large fluid-containing blister > 1 cm Pustular psoriasis G Wheal Vesicle containing pus Hives (urticaria) H Scale Transient smooth papule or plaque Eczema, psoriasis, SCC I Flaking off of stratum corneum Impetigo J Crust Dry exudate DE ABC F GH I J Dermatologic microscopic terms LESION CHARACTERISTICS EXAMPLES Dyskeratosis Abnormal premature keratinization Squamous cell carcinoma Psoriasis, calluses Hyperkeratosis \u008f thickness of stratum corneum Psoriasis, actinic keratosis Lichen planus Parakeratosis Retention of nuclei in stratum corneum Eczematous dermatitis Hypergranulosis \u008f\u00a0thickness of stratum granulosum Pemphigus vulgaris Acanthosis nigricans, psoriasis Spongiosis Epidermal accumulation of edematous fluid in intercellular spaces Acantholysis Separation of epidermal cells Acanthosis Epidermal hyperplasia (\u008f spinosum) uploaded by medbooksvn","484 SECTION III Musculoskeletal, Skin, and Connec tive Tissue\u2003 \uf07d\u2009Dermatology Pigmented skin disorders Albinism Normal melanocyte number with \u0090 melanin production A due to \u0090 tyrosinase activity or defective tyrosine transport. \u008f risk of skin cancer. Melasma (chloasma) Acquired hyperpigmentation associated with pregnancy (\u201cmask of pregnancy\u201d B ) or OCP use. More common in patients with darker skin tones. Vitiligo Irregular patches of complete depigmentation C . Caused by destruction of melanocytes (believed to be autoimmune). Associated with other autoimmune disorders. Waardenburg Patchy depigmentation of skin, hair, and irises that can be associated with deafness. Caused by syndrome defects in the differentiation of neural crest cells into melanocytes. ABC Seborrheic dermatitis Erythematous, well-demarcated plaques A with greasy yellow scales in areas rich in sebaceous A glands, such as scalp, face, and periocular region. Common in both infants (cradle cap) and adults, associated with Parkinson disease. Sebaceous glands are not inflamed, but play a role in disease development. Possibly associated with Malassezia spp. Treatment: topical antifungals and glucocorticoids.","Musculoskeletal, Skin, and Connec tive Tissue\u2003 \uf07d\u2009Dermatology SECTION III 485 Common skin disorders Acne Multifactorial etiology\u2014\u008f sebum\/androgen production, abnormal keratinocyte desquamation, Cutibacterium acnes colonization of the pilosebaceous unit (comedones), and inflammation (papules\/pustules A , nodules, cysts). Treatment: retinoids, benzoyl peroxide, and antibiotics. Atopic dermatitis Pruritic eruption associated with ichthyosis vulgaris and other atopic diseases (asthma, allergic rhi- (eczema) nitis, food allergies); \u008f\u00a0serum IgE. Often appears on face in infancy B and then on flexural surfaces C in children and adults. Allergic contact Type IV hypersensitivity reaction secondary to contact allergen (eg, nickel D , poison ivy E , neomycin). dermatitis Keratosis pilaris Follicular-based papules from keratin plugging, most often on extensor surfaces of arms and thighs. Melanocytic nevus Common mole. Benign, but melanoma can arise in congenital or atypical moles. Intradermal nevi are papular F . Junctional nevi are flat macules G . Pseudofolliculitis Inflammatory reaction to hair penetrating the skin characterized by firm papules and pustules that barbae are painful and pruritic. Commonly occurs near jawline as a result of shaving (\u201crazor bumps\u201d), more common with naturally curly hair. Psoriasis Papules and plaques with silvery scaling H , especially on knees and elbows. Acanthosis with parakeratotic scaling (nuclei still in stratum corneum), Munro microabscesses. \u008f stratum spinosum, \u0090 stratum granulosum. Auspitz sign ( I )\u2014pinpoint bleeding spots from exposure of dermal papillae when scales are scraped off. Associated with nail pitting and psoriatic arthritis. Rosacea Inflammatory facial skin disorder characterized by erythematous papules and pustules J , but no comedones. May be associated with facial flushing in response to external stimuli (eg, alcohol, heat). Complications include ocular involvement, rhinophyma (bulbous deformation of nose). Seborrheic keratosis Well-demarcated, verrucous, benign squamous epithelial proliferation of immature keratinocytes with keratin-filled cysts (horn cysts) K . Looks \u201cstuck on.\u201d Leser-Tr\u00e9lat sign L \u2014rapid onset of multiple seborrheic keratoses, indicates possible malignancy (eg, GI adenocarcinoma). Verrucae Warts; caused by low-risk HPV strains. Soft, tan-colored, cauliflowerlike papules M. Epidermal hyperplasia, hyperkeratosis, koilocytosis. Condyloma acuminatum on anus or genitals N . Urticaria Hives. Pruritic wheals that form after mast cell degranulation O . Characterized by superficial dermal edema and lymphatic channel dilation. A B CD E FGHI J K L MN O uploaded by medbooksvn","486 SECTION III Musculoskeletal, Skin, and Connec tive Tissue\u2003 \uf07d\u2009Dermatology Vascular tumors of skin Angiosarcoma Rare blood vessel malignancy typically occurring in the head, neck, and breast areas. Usually in older adults, on sun-exposed areas. Associated with radiation therapy and chronic postmastectomy lymphedema. Stewart-Treves syndrome\u2014cutaneous angiosarcoma developing after chronic lymphedema. Hepatic angiosarcoma associated with vinyl chloride and arsenic exposures. Very aggressive and difficult to resect due to delay in diagnosis. Bacillary angiomatosis Benign capillary skin papules A found in patients with AIDS. Caused by Bartonella infections. Frequently mistaken for Kaposi sarcoma, but has neutrophilic infiltrate. Cherry angioma Benign capillary hemangioma B commonly appearing in middle-aged adults. Does not regress. Frequency \u008f with age. Glomus tumor Benign, painful, red-blue tumor, commonly under fingernails C . Arises from modified smooth muscle cells of the thermoregulatory glomus body. Kaposi sarcoma Endothelial malignancy most commonly affecting the skin, mouth, GI tract, respiratory tract. Classically seen in older Eastern European males, patients with AIDS, and organ transplant patients. Associated with HHV-8 and HIV. Lymphocytic infiltrate, unlike bacillary angiomatosis. Pyogenic granuloma Polypoid lobulated capillary hemangioma D that can ulcerate and bleed. Associated with trauma and pregnancy. Strawberry (infantile) Benign capillary hemangioma of infancy E . Appears in first few weeks of life (1\/200 births); grows hemangioma rapidly and regresses spontaneously by 5\u20138 years old. Strawberry hemangioma spontaneously regresses; cherry angioma cannot. A B CDE","Musculoskeletal, Skin, and Connec tive Tissue\u2003 \uf07d\u2009Dermatology SECTION III 487 Skin infections Skin infection involving superficial epidermis. Usually from S aureus or S pyogenes. Highly Bacterial infections contagious. Honey-colored crusting A . Impetigo Bullous impetigo B has bullae and is usually caused by S aureus. Erysipelas Cellulitis Infection involving upper dermis and superficial lymphatics, usually from S pyogenes. Presents with Abscess well-defined, raised demarcation between infected and normal skin C . Necrotizing fasciitis Acute, painful, spreading infection of deeper dermis and subcutaneous tissues. Usually from Staphylococcal S\u00a0pyogenes or S aureus. Often starts with a break in skin from trauma or another infection D . scalded skin syndrome Collection of pus from a walled-off infection within deeper layers of skin E . Offending organism is almost always S aureus. Viral infections Herpes Deeper tissue injury, usually from anaerobic bacteria or S pyogenes. Pain may be out of proportion Molluscum to exam findings. Results in crepitus from methane and CO2 production. \u201cFlesh-eating bacteria.\u201d contagiosum Causes bullae and skin necrosis \u008e violaceous color of bullae, surrounding skin F . Surgical Varicella zoster emergency. Hairy leukoplakia Exotoxin destroys keratinocyte attachments in stratum granulosum only (vs toxic epidermal necrolysis, which destroys epidermal-dermal junction). No mucosal involvement. Characterized A by fever and generalized erythematous rash with sloughing of the upper layers of the epidermis G that heals completely. \u2295\u00a0Nikolsky sign (separation of epidermis upon manual stroking of skin). Commonly seen in newborns and children\/adults with renal insufficiency. Herpes virus infections (HSV-1 and HSV-2) of skin can occur anywhere from mucosal surfaces to normal skin. These include herpes labialis, herpes genitalis, herpetic whitlow H (finger). Umbilicated papules I caused by a poxvirus. While frequently seen in children, it may be sexually transmitted in adults. Causes varicella (chickenpox) and zoster (shingles). Varicella presents with multiple crops of lesions in various stages from vesicles to crusts. Zoster is a reactivation of the virus in dermatomal distribution (unless it is disseminated). Irregular, white, painless plaques on lateral tongue that cannot be scraped off J . EBV mediated. Occurs in patients living with HIV, organ transplant recipients. Contrast with thrush (scrapable) and leukoplakia (precancerous). BCDE F GH I J uploaded by medbooksvn","488 SECTION III Musculoskeletal, Skin, and Connec tive Tissue\u2003 \uf07d\u2009Dermatology Cutaneous mycoses Clinical name for dermatophyte (cutaneous fungal) infections. Dermatophytes include Tinea Microsporum, Trichophyton, and Epidermophyton. Branching septate hyphae visible on KOH (dermatophytes) preparation with blue fungal stain A . Associated with pruritus. Tinea capitis Occurs on head, scalp. Associated with lymphadenopathy, alopecia, scaling B . Tinea corporis Occurs on body (usually torso). Characterized by enlarging erythematous, scaly rings (\u201cringworm\u201d) Tinea cruris with central clearing C . Can be acquired from contact with infected pets or farm animals. Tinea pedis Occurs in inguinal area (\u201cjock itch\u201d) D . Often does not show the central clearing seen in tinea corporis. Tinea unguium Tinea (pityriasis) Three varieties (\u201cathlete\u2019s foot\u201d): versicolor \u0083\t Interdigital E ; most common \u0083\t Moccasin distribution F \u0083\t Vesicular type Onychomycosis; occurs on nails. Caused by Malassezia spp. (Pityrosporum spp.), a yeastlike fungus (not a dermatophyte despite being called tinea). Degradation of lipids produces acids that inhibit tyrosinase (involved in melanin synthesis) \u008e hypopigmentation G ; hyperpigmentation and\/or pink patches can also occur due to inflammatory response. Less pruritic than dermatophytes. Can occur any time of year, but more common in summer (hot, humid weather). \u201cSpaghetti and meatballs\u201d appearance on microscopy H . Treatment: selenium sulfide, topical and\/or oral antifungal medications. A B CD EF GH","Musculoskeletal, Skin, and Connec tive Tissue\u2003 \uf07d\u2009Dermatology SECTION III 489 Autoimmune blistering skin disorders Pemphigus vulgaris Bullous pemphigoid Less severe than pemphigus vulgaris. Most PATHOPHYSIOLOGY Potentially fatal. Most commonly seen in older adults. Type II hypersensitivity reaction. commonly seen in older adults. Type II hypersensitivity reaction. IgG antibodies against desmogelin 3 +\/\u2013 IgG antibodies against hemidesmosomes desmoglein 1 (component of desmosomes, (epidermal basement membrane; antibodies which connect keratinocytes in the stratum are \u201cbullow\u201d the epidermis). spinosum). Tense blisters C containing eosinophils; oral mucosa spared. Nikolsky sign \u229d. GROSS MORPHOLOGY Flaccid intraepidermal bullae A caused by acantholysis (separation of keratinocytes, \u201crow Linear pattern at epidermal-dermal junction D . of tombstones\u201d on H&E stain); oral mucosa is involved. Nikolsky sign \u2295. IMMUNOFLUORESCENCE Reticular pattern around epidermal cells B . A B CD Normal Epidermis Basal Disrupted Dermis layer desmosomes Basement membrane Intact Intact desmosomes (ECM\/collagen) hemidesmosomes IgG antibodies Disrupted hemidesmosomes Epidermolysis bullosa Autosomal dominant defect in keratin filament assembly \u008e cytoskeleton disruption \u008e epithelial simplex fragility. Presents early in life with friction-induced skin blistering that primarily affects palms and soles. Heals without scarring. Skin biopsy: intraepidermal cleavage. uploaded by medbooksvn","490 SECTION III Musculoskeletal, Skin, and Connec tive Tissue\u2003 \uf07d\u2009Dermatology Other blistering skin disorders Dermatitis Pruritic papules, vesicles, and bullae (often found on elbows, knees, buttocks) A . Deposits of IgA at herpetiformis tips of dermal papillae. Associated with celiac disease. Treatment: dapsone, gluten-free diet. Erythema multiforme Associated with infections (eg, Mycoplasma pneumoniae, HSV), drugs (eg, sulfa drugs, \u03b2-lactams, phenytoin). Presents with multiple types of lesions\u2014macules, papules, vesicles, target lesions (look like targets with multiple rings and dusky center showing epithelial disruption) B . Stevens-Johnson Characterized by fever, bullae formation and necrosis, sloughing of skin at dermal-epidermal syndrome junction (\u2295 Nikolsky), high mortality rate. Typically mucous membranes are involved C . Targetoid skin lesions may appear, as seen in erythema multiforme. Usually associated with adverse drug reaction. Toxic epidermal necrolysis (TEN) D E is more severe form of SJS involving > 30% body surface area. 10\u201330% involvement denotes SJS-TEN. AB CD E Cutaneous ulcers Venous ulcer Arterial ulcer Neuropathic ulcer Pressure injury Chronic venous Peripheral artery Peripheral neuropathy ETIOLOGY Prolonged unrelieved insufficiency; most disease (eg, (eg,\u00a0diabetic foot) pressure (eg, LOCATION common ulcer type atherosclerotic immobility) APPEARANCE stenosis) Bony prominences Gaiter area (ankle to Distal toes, anterior (eg,\u00a0metatarsal Weightbearing points PAIN midcalf), typically shin, pressure points heads, heel) (eg, sacrum, ischium, ASSOCIATED SIGNS over malleoli calcaneus) Symmetric with well- Hyperkeratotic edge Irregular border, defined punched-out with undermined Varies based on stage shallow, exudative A appearance B borders C from non-blanchable erythema to full- Mild to moderate Severe Absent thickness skin loss D Telangiectasias, Arterial insufficiency, Claw toes, Charcot Present varicose veins, cold and pale joints, absent reflexes edema, stasis atrophic skin, hair Soft tissue infection dermatitis loss, absent pulses and osteomyelitis (erythematous are frequent eczematous patches) complications ABCD","Musculoskeletal, Skin, and Connec tive Tissue\u2003 \uf07d\u2009Dermatology SECTION III 491 Miscellaneous skin disorders Acanthosis nigricans Epidermal hyperplasia causing symmetric, hyperpigmented thickening of skin, especially in axilla or on neck A . Associated with insulin resistance (eg, diabetes, obesity, Cushing syndrome, PCOS), visceral malignancy (eg, gastric adenocarcinoma). Erythema nodosum Painful, raised inflammatory lesions of subcutaneous fat (panniculitis), usually on anterior shins. Often idiopathic, but can be associated with sarcoidosis, coccidioidomycosis, histoplasmosis, TB, streptococcal infections B , leprosy C , inflammatory bowel disease. Ichthyosis vulgaris Disorder of defective keratinocyte desquamation due to filaggrin gene mutations resulting in diffuse scaling of the skin D most commonly on the extensor side of extremities and the trunk. Manifests in infancy or early childhood. Strong association with atopic dermatitis. Lichen Planus Pruritic, purple, polygonal planar papules and plaques are the 6 P\u2019s of lichen Planus E F . Mucosal involvement manifests as Wickham striae (reticular white lines) and hypergranulosis. Sawtooth infiltrate of lymphocytes at dermal-epidermal junction. Associated with hepatitis C. Pityriasis rosea \u201cHerald patch\u201d G followed days later by other scaly erythematous plaques, often in a \u201cChristmas tree\u201d distribution on trunk H . Multiple pink plaques with collarette scale. Self-resolving in 6\u20138 weeks. Sunburn Acute cutaneous inflammatory reaction due to excessive UV irradiation. Causes DNA mutations, inducing apoptosis of keratinocytes. UVB is dominant in sunBurn, UVA in tAnning and photoAging. Exposure to UVA and UVB \u008f\u00a0risk of skin cancer. A BC D E FG H uploaded by medbooksvn","492 SECTION III Musculoskeletal, Skin, and Connec tive Tissue\u2003 \uf07d\u2009Dermatology Estimation of body Approximated by the rule of 9\u2019s. Used to assess the extent of burn injuries. surface area 4.5 Entire head 4.5 9% Entire thorax 18% 99 Entire arm (L) 9% 4.5 4.5 Entire arm (R) 9% 4.5 4.5 9 Entire 9 abdomen 18% 1 99 Perineum 99 1% Entire leg (L) 18% Entire leg (R) 18% Total 100% Burn classifi ation INVOLVEMENT APPEARANCE SENSATION DEPTH Epidermis only Similar to sunburn; histamine release Painful causes localized, dry, blanching Superficial burn Epidermis and papillary dermis redness without blisters Painful to temperature and air Superficial partial- Epidermis and reticular dermis Blisters, blanches with pressure, thickness burn swollen, warm Painless; perception of Deep partial- Epidermis and full-thickness pressure only thickness burn dermis Blisters (easily unroofed), does not Full-thickness burn blanch with pressure Painless; perception of Epidermis, dermis, and involvement deep pressure only Deeper injury burn of underlying tissue (eg, fascia, White, waxy, dry, inelastic, leathery, muscle) does not blanch with pressure Painless; some perception of deep White, dry, inelastic, does not blanch pressure with pressure","Musculoskeletal, Skin, and Connec tive Tissue\u2003 \uf07d\u2009DERMATOLOGY SECTION III 493 Skin cancer Basal cell carcinoma (BCC) more common above upper lip. Basal cell carcinoma Squamous cell Squamous cell carcinoma (SCC) more common below lower carcinoma lip. Melanoma Sun exposure strongly predisposes to skin cancer. Most common skin cancer. Found in sun-exposed areas of body (eg, face). Locally invasive, but rarely metastasizes. Waxy, pink, pearly nodules, commonly with telangiectasias, rolled borders A , central crusting or ulceration. BCCs also appear as nonhealing ulcers with infiltrating growth B or as a scaling plaque (superficial BCC) C . Basal cell tumors have \u201cpalisading\u201d (aligned) nuclei D . Second most common skin cancer. Associated with immunosuppression, chronic nonhealing wounds, and occasionally arsenic exposure. Marjolin ulcer\u2014SCC arising in chronic wounds or scars; usually develops > 20 years after insult. Commonly appears on face E , lower lip F , ears, hands. Locally invasive, may spread to lymph nodes, and will rarely metastasize. Ulcerative red lesions. Histopathology: keratin \u201cpearls\u201d\u00a0 G . Actinic keratosis\u2014Premalignant lesions caused by sun exposure. Small, rough, erythematous or brownish papules or plaques H . Risk of squamous cell carcinoma is proportional to degree of epithelial dysplasia. Common tumor with significant risk of metastasis. S-100 tumor marker. Associated with dysplastic nevi; people with lighter skin tones are at \u008f risk. Depth of tumor (Breslow thickness) correlates with risk of metastasis. Look for the ABCDEs: Asymmetry, Border irregularity, Color variation, Diameter > 6 mm, and Evolution over time. At least 4 different types of melanoma, including superficial spreading I , nodular J , lentigo maligna K , and acral lentiginous (highest prevalence in people with darker skin tones) L . Often driven by activating mutation in BRAF kinase. Primary treatment is excision with appropriately wide margins. Advanced melanoma also treated with immunotherapy (eg, ipilimumab) and\/or BRAF inhibitors (eg, vemurafenib). AB C D E FGH I JKL uploaded by medbooksvn","494 SECTION III Musculoskeletal, Skin, and Connec tive Tissue\u2003 \uf07d\u2009pharmacology `\u2009MUSCULOSKELETAL, SKIN, AND CONNECTIVE TISSUE\u2014PHARMACOLOGY Arachidonic acid pathways MEMBRANE PHOSPHOLIPIDS Phospholipase A2 ANTI-INFLAMMATORY AGENTS Glucocorticoids (corticosteroids) LEUKOTRIENE Arachidonic acid NF-\u03baB ENDOPEROXIDE SYNTHESIS SYNTHESIS I\u03baB (cyclooxygenase) (5-lipoxygenase) COX-2 COX-2 ONLY COX-1, COX-2 COX-1 Celecoxib Zileuton Aspirin (irreversible) 5-Lipoxygenase Other NSAIDs (reversible) LEUKOTRIENE RECEPTOR Diclofenac KeKteotroorloalcac Ibuprofen NNaparporxoexnen ANTAGONISTS Indomethacin Montelukast 5-HPETE Cyclic endoperoxides Za\ufb01rlukast L eukotrienes Prostacyclin Prostaglandins Thromboxane LTC4 LTD4 LTE4 LTB4 PGI2 PGE1 PGE2 PGF2\u03b1 TXA2 bronchial tone neutrophil platelet platelet chemotaxis aggregation vascular uterine uterine aggregation vascular tone tone tone tone vascular tone Epoprostenol Alprostadil Dinoprostone Carboprost LTB4 is a neutrophil chemotactic agent. Neutrophils arrive \u201cB4\u201d others. PGI2 is a vasodilator and platelet aggregation Platelet-Gathering Inhibitor. inhibitor. Acetaminophen Reversibly inhibits cyclooxygenase, mostly in CNS. Inactivated peripherally. MECHANISM Antipyretic, analgesic, but not anti-inflammatory. Used instead of aspirin to avoid Reye syndrome CLINICAL USE in children with viral infection. ADVERSE EFFECTS Overdose produces hepatic necrosis; acetaminophen metabolite (NAPQI) depletes glutathione and forms toxic tissue byproducts in liver. N-acetylcysteine is antidote\u2014regenerates glutathione.","Musculoskeletal, Skin, and Connec tive Tissue\u2003 \uf07d\u2009pharmacology SECTION III 495 Aspirin NSAID that irreversibly (Aspirin) inhibits cyclooxygenase (both COX-1 and COX-2) by covalent acetylation \u008e\u00a0\u0090\u00a0synthesis of TXA2 and prostaglandins. \u008f\u00a0bleeding time. No effect on PT, PTT. MECHANISM Effect lasts until new platelets are produced. CLINICAL USE Low dose (< 300 mg\/day): \u0090 platelet aggregation. Intermediate dose (300\u20132400 mg\/day): antipyretic ADVERSE EFFECTS and analgesic. High dose (2400\u20134000 mg\/day): anti-inflammatory. Celecoxib Gastric ulceration, tinnitus (CN VIII), allergic reactions (especially in patients with asthma or nasal polyps). Chronic use can lead to acute kidney injury, interstitial nephritis, GI bleeding. Risk of MECHANISM Reye syndrome in children treated for viral infection. Toxic doses cause respiratory alkalosis early, but transitions to mixed metabolic acidosis-respiratory alkalosis. Overdose treatment: NaHCO3. CLINICAL USE ADVERSE EFFECTS Reversibly and selectively inhibits the cyclooxygenase (COX) isoform 2 (\u201cSelecoxib\u201d), which is found in inflammatory cells and vascular endothelium and mediates inflammation and pain; Nonsteroidal spares COX-1, which helps maintain gastric mucosa. Thus, does not have the corrosive effects anti-inflamm tory of other NSAIDs on the GI lining. Spares platelet function as TXA2 production is dependent on drugs COX-1. MECHANISM Rheumatoid arthritis, osteoarthritis. CLINICAL USE \u008f risk of thrombosis, sulfa allergy. ADVERSE EFFECTS Ibuprofen, naproxen, indomethacin, ketorolac, diclofenac, meloxicam, piroxicam. Leflunomid Reversibly inhibit cyclooxygenase (both COX-1 and COX-2). Block prostaglandin synthesis. MECHANISM Antipyretic, analgesic, anti-inflammatory. Indomethacin is used to close a PDA. CLINICAL USE Interstitial nephritis, gastric ulcer (prostaglandins protect gastric mucosa), renal ischemia ADVERSE EFFECTS (prostaglandins vasodilate afferent arteriole), aplastic anemia. Bisphosphonates Reversibly inhibits dihydroorotate dehydrogenase, preventing pyrimidine synthesis. Suppresses MECHANISM T-cell proliferation. CLINICAL USE ADVERSE EFFECTS Rheumatoid arthritis, psoriatic arthritis. Diarrhea, hypertension, hepatotoxicity, teratogenicity. Alendronate, ibandronate, risedronate, zoledronate. Pyrophosphate analogs; bind hydroxyapatite in bone, inhibiting osteoclast activity. Osteoporosis, hypercalcemia, Paget disease of bone, metastatic bone disease, osteogenesis imperfecta. Esophagitis, osteonecrosis of jaw, atypical femoral stress fractures. uploaded by medbooksvn","496 SECTION III Musculoskeletal, Skin, and Connec tive Tissue\u2003 \uf07d\u2009pharmacology Teriparatide Recombinant PTH analog. \u008f\u00a0osteoblastic activity when administered in pulsatile fashion. Osteoporosis. Causes \u008f\u00a0bone growth compared to antiresorptive therapies (eg, bisphosphonates). MECHANISM Dizziness, tachycardia, transient hypercalcemia, muscle spasms. CLINICAL USE ADVERSE EFFECTS Gout drugs Chronic gout drugs (preventive) Allopurinol Competitive inhibitor of xanthine oxidase All painful flares are preventable. \u008e\u00a0\u0090\u00a0conversion of hypoxanthine and xanthine to urate. Also used in lymphoma and leukemia Purines to prevent tumor lysis\u2013associated urate nephropathy. \u008f concentrations of xanthine Hypoxanthine Allopurinol, oxidase active metabolites, azathioprine, and Febuxostat 6-MP. Xanthine oxidase Pegloticase Recombinant uricase catalyzing uric acid to allantoin (a more water-soluble product). Xanthine Xanthine Febuxostat Inhibits xanthine oxidase. Think, \u201cfebu-xo-stat oxidase makes Xanthine Oxidase static.\u201d Plasma uric acid Probenecid Inhibits reabsorption of uric acid in proximal convoluted tubule (also inhibits secretion of penicillin). Can precipitate uric acid calculi or Tubular secretion Tubular reabsorption lead to sulfa allergy. Acute gout drugs Diuretics, Probenecid, low-dose salicylates high-dose salicylates NSAIDs Any NSAID. Use salicylates with caution (may decrease uric acid excretion, particularly at Urine low doses). Glucocorticoids Oral, intra-articular, or parenteral. Colchicine Binds and stabilizes tubulin to inhibit microtubule polymerization, impairing neutrophil chemotaxis and degranulation. Acute and prophylactic value. GI, neuromyopathic adverse effects. Can also cause myelosuppression, nephrotoxicity.","Musculoskeletal, Skin, and Connec tive Tissue\u2003 \uf07d\u2009pharmacology SECTION III 497 TNF-\u03b1 inhibitors MECHANISM CLINICAL USE ADVERSE EFFECTS DRUG Fusion protein (decoy receptor Rheumatoid arthritis, psoriasis, Predisposition to infection, for TNF-\u03b1 + IgG1 Fc), ankylosing spondylitis. including reactivation of Etanercept produced by recombinant latent TB, since TNF is DNA. Inflammatory bowel disease, important in granuloma Adalimumab, rheumatoid arthritis, formation and stabilization. certolizumab, Etanercept intercepts TNF. ankylosing spondylitis, golimumab, psoriasis. Can also lead to drug-induced infliximab Anti-TNF-\u03b1 monoclonal lupus. antibody. Imiquimod Binds toll-like receptor 7 (TLR-7) of macrophages, monocytes, and dendritic cells to activate them MECHANISM \u008e topical antitumor immune response modifier. CLINICAL USE Anogenital warts, actinic keratosis. ADVERSE EFFECTS Itching, burning pain at site of application, rashes. uploaded by medbooksvn","498 SECTION III M\ufeff USCULOSKELETAL, SKIN, AND CONNECTIVE TISSUE\u2003 \uf07d\u2009pharmacology ` \u2009N O T E S","HIGH-YIELD SYSTEMS Neurology and Special Senses \u201cWe are all now connected by the Internet, like neurons in a giant brain.\u201d `\tEmbryology\t 500 \u2014Stephen Hawking `\tAnatomy and 503 \u201cExactly how [the brain] operates remains one of the biggest unsolved Physiology\t 526 mysteries, and it seems the more we probe its secrets, the more surprises we `\tPathology\t 549 find.\u201d `\tOtology\t 551 `\tOphthalmology\t 561 \u2014Neil deGrasse Tyson `\tPharmacology\t \u201cIt\u2019s not enough to be nice in life. You\u2019ve got to have nerve.\u201d \u2014Georgia O\u2019Keeffe \u201cI not only use all the brains that I have, but all that I can borrow.\u201d \u2014Woodrow Wilson \u201cThe chief function of the body is to carry the brain around.\u201d \u2014Thomas Edison \u201cI opened two gifts this morning. They were my eyes.\u201d \u2014Hilary Hinton \u201cZig\u201d Ziglar Understand the difference between the findings and underlying anatomy of upper motor neuron and lower motor neuron lesions. Know the major motor, sensory, cerebellar and visual pathways and their respective locations in the CNS. Connect key neurological associations with certain pathologies (eg, cerebellar lesions, stroke manifestations, Brown-S\u00e9quard syndrome). Recognize common findings on MRI\/CT (eg, ischemic and hemorrhagic stroke) and on neuropathology (eg, neurofibrillary tangles and Lewy bodies). High-yield medications include those used to treat epilepsy, Parkinson disease, migraine, and pain (eg, opioids). 499 uploaded by medbooksvn","500 SEC TION III Neurology and Special Senses\u2003 \uf07d\u2009neurology\u2014Embryology ` \u2009NEUROLOGY \u2014 EMBRYOLOGY Neural development Notochord induces overlying ectoderm to differentiate into neuroectoderm and form neural plate. Notochord becomes nucleus pulposus of intervertebral disc in adults. Neural plate Neural plate gives rise to neural tube and neural crest cells. Lateral walls of neural tube are divided into alar and basal plates. Notochord Neural fold Alar plate (dorsal): sensory; induced by bone Bmasoalrpphlaotgee(nveetnitcraplr)o: tmeiontso(rB; iMndPus)c\ted by \tSame orientation as spinal cord Neural tube Neural crest sonic hedgehog (SHH) cells Neuro\u2013Regionalization of neural tube.pdf 1 11\/8\/22 11:49 AM Regionalization of Telencephalon is the 1st part. Diencephalon is the 2nd part. The rest are arranged alphabetically: neural tube mesencephalon, metencephalon, myelencephalon. Three primary Five secondary vesicles Adult derivatives of: vesicles Walls Cavities Wall Cavity Telencephalon Cerebral Lateral Diencephalon hemispheres ventricle Forebrain Mesencephalon Basal ganglia Third (prosencephalon) ventricle Metencephalon Thalamus Midbrain Myelencephalon Hypothalamus Cerebral (mesencephalon) Retina aqueduct Midbrain Upper part of Hindbrain fourth ventricle (rhombencephalon) Pons Lower part of fourth ventricle Cerebellum Medulla Spinal cord Central and peripheral Neuroepithelia in neural tube\u2014CNS neurons, CNS glial cells (astrocytes, oligodendrocytes, nervous systems ependymal cells). origins Neural crest\u2014PNS neurons (dorsal root ganglia, autonomic ganglia [sympathetic, parasympathetic, enteric]), PNS glial cells (Schwann cells, satellite cells), adrenal medulla. Mesoderm\u2014microglia (like macrophages).","Neurology and Special Senses\u2003 \uf07d\u2009neurology\u2014Embryology SEC TION III 501 Neural tube defects Failure of neural tube to close completely by week 4 of development. Associated with maternal folate deficiency during pregnancy. Diagnosis: ultrasound, maternal serum AFP (\u008f\u00a0in open Spinal dysraphism NTDs). Spina bifida occulta Closed NTD. Failure of caudal neural tube to close, but no herniation. Dura is intact. Usually seen Meningocele at lower vertebral levels. Associated with tuft of hair or skin dimple at level of bony defect. Myelomeningocele Myeloschisis Open NTD. Meninges (but no neural tissue) herniate through bony defect. Cranial dysraphism Open NTD. Meninges and neural tissue (eg, cauda equina) herniate through bony defect. Anencephaly Open NTD. Exposed, unfused neural tissue without skin\/meningeal covering. Open NTD. Failure of rostral neuropore to close \u008e\u00a0no forebrain, open calvarium. Often presents with polyhydramnios (\u0090\u00a0fetal swallowing due to lack of neural control). +\/\u2212 Tuft of hair Skin defect\/thinning Skin thin or absent Skin +\/\u2212 Skin dimple Subarachnoid Dura space Leptomeninges Spinal Transverse cord process Normal Spina bi\ufb01da occulta Meningocele Myelomeningocele Brain malformations Often incompatible with postnatal life. Survivors may be profoundly disabled. Holoprosencephaly Failure of forebrain (prosencephalon) to divide A B Lissencephaly into 2 cerebral hemispheres; developmental \u2003 field defect usually occurring at weeks 3\u20134 of development. Associated with SHH mutations. May be seen in Patau syndrome (trisomy 13), fetal alcohol syndrome. Presents with midline defects: monoventricle A , fused basal ganglia, cleft lip\/palate, hypotelorism, cyclopia, proboscis. \u008f\u00a0risk for pituitary dysfunction (eg, diabetes insipidus). Failure of neuronal migration \u008e\u00a0smooth brain surface that lacks sulci and gyri B . Presents with dysphagia, seizures, microcephaly, facial anomalies. uploaded by medbooksvn","502 SEC TION III Neurology and Special Senses\u2003 \uf07d\u2009neurology\u2014Embryology Posterior fossa malformations Chiari I malformation Downward displacement of cerebellar tonsils through foramen magnum (1 structure) A . Usually asymptomatic in childhood, manifests in adulthood with headaches and cerebellar symptoms. Associated with spinal cord cavitations (eg, syringomyelia). Chiari II malformation Downward displacement of cerebellum (vermis and tonsils) and medulla (2 structures) through foramen magnum \u008e\u00a0noncommunicating hydrocephalus. More severe than Chiari I, usually presents early in life with dysphagia, stridor, apnea, limb weakness. Associated with myelomeningocele (usually lumbosacral). Dandy-Walker Agenesis of cerebellar vermis \u008e\u00a0cystic enlargement of 4th ventricle (arrow in B ) that fills the malformation enlarged posterior fossa. Associated with noncommunicating hydrocephalus, spina bifida. AB Chiari I malformation Syrinx Syringomyelia Fluid-filled, gliosis-lined cavity within spinal Syrinx (Greek) = tube, as in \u201csyringe.\u201d A cord (yellow arrows in A ). Fibers crossing in Most lesions occur between C2 and T9. anterior white commissure (spinothalamic Usually associated with Chiari I malformation tract) are typically damaged first \u008e\u00a0\u201ccape- like\u201d loss of pain and temperature sensation in (red arrow in A ). Less commonly associated bilateral upper extremities. As lesion expands it with other malformations, infections, tumors, may damage anterior horns \u008e\u00a0LMN deficits. trauma. Dorsal root ganglion Loss of pain and temperature sensation at a ected dermatomes C5-T4 shown here Expanding syrinx can a ect multiple dermatomes A erent Lateral spinothalamic tract pain, temperature Anterior white commissure compressed by syrinx","Neurology and Special Senses\u2003 \uf07d\u2009neurology\u2014Anatomy and Physiology SEC TION III 503 Tongue development 1st pharyngeal arch forms anterior 2\/3 of tongue Taste\u2014CN VII, IX, X (nucleus tractus solitarius (sensation via CN V3, taste via CN VII). [NTS]). Taste Arches Sensation CN X 3 and 4 CN X 3rd and 4th pharyngeal arches form posterior Pain\u2014CN V3, IX, X. 1\/3 of tongue (sensation and taste mainly via Motor\u2014CN X, XII. CN IX CN IX CN IX, extreme posterior via CN\u00a0X). The genie comes out of the lamp in style. Arch 1 Motor innervation is via CN XII to hyoglossus (retracts and depresses tongue), genioglossus CN 10 innervates palatenglossus. CN VII CN V\u2083 (protrudes tongue), and styloglossus (draws sides of tongue upward to create a trough for swallowing). Motor innervation is via CN X to palatoglossus (elevates posterior tongue during swallowing). `\u2009NEUROLOGY\u2014ANATOMY AND PHYSIOLOGY Neurons Signal-transmitting cells of the nervous system. Permanent cells\u2014do not divide in adulthood. Signal-relaying cells with dendrites (receive input), cell bodies, and axons (send output). Cell bodies and dendrites can be seen on Nissl staining (stains RER). RER is not present in the axon. Neuron markers: neurofilament protein, synaptophysin. Astrocytes Largest and most abundant glial cell in CNS. Derived from neuroectoderm. Physical support, repair, removal of excess GFAP \u2295. neurotransmitter, component of blood-brain barrier, glycogen fuel reserve buffer. Reactive gliosis in response to neural injury. Microglia Phagocytic scavenger cells of CNS. Activation Derived from mesoderm. in response to tissue damage \u008e\u00a0release of HIV-infected microglia fuse to form inflammatory mediators (eg, nitric oxide, glutamate). Not readily discernible by Nissl multinucleated giant cells in CNS in HIV- stain. associated dementia. Ependymal cells Ciliated simple columnar glial cells lining Derived from neuroectoderm. ventricles and central canal of spinal cord. Specialized ependymal cells (choroid plexus) Apical surfaces are covered with cilia (which circulate CSF) and microvilli (which help with produce CSF. CSF absorption). uploaded by medbooksvn","504 SEC TION III Neurology and Special Senses\u2003 \uf07d\u2009neurology\u2014Anatomy and Physiology Myelin \u008f conduction velocity of signals transmitted Myelin wraps and insulates axons: \u0090\u00a0membrane down axons \u008e\u00a0saltatory conduction of action capacitance, \u008f\u00a0membrane resistance, \u008f\u00a0space potential at the nodes of Ranvier, where there (length) constant, \u0090\u00a0time constant. are high concentrations of Na+ channels. CNS: Oligodendrocytes. In CNS (including CN II), myelin is synthesized PNS: Schwann cells. COPS by oligodendrocytes; in PNS (including CN III-XII), myelin is synthesized by Schwann cells. Schwann cells Promote axonal regeneration. Derived from Each \u201cSchwone\u201d cell myelinates only 1 PNS axon. Nucleus Schwann cell neural crest. Injured in Guillain-Barr\u00e9 syndrome. Schwann cell marker: S100. Myelin sheath Node of Ranvier Oligodendrocytes Myelinate axons of neurons in CNS. Each Derived from neuroectoderm. oligodendrocyte can myelinate many axons \u201cFried egg\u201d appearance histologically. Node of Ranvier (\u223c 30). Predominant type of glial cell in white Injured in multiple sclerosis, progressive matter. Oligodendrocyte multifocal leukoencephalopathy (PML), leukodystrophies.","Neurology and Special Senses\u2003 \uf07d\u2009neurology\u2014Anatomy and Physiology SEC TION III 505 Neuron action potential Voltage-gated Voltage-gated Na+ channel K+ channel + 40 0 Na+ Extracellular Membrane potential 1 Na+ relative permeability Intracellular Na+ K+ 23 Activation gate Inactivation Membrane potential (mV) gate 2 \u201355 Threshold potential K+ relative permeability K+ Na+ Resting potential 3 \u201375 K+ \u2013100 1 4 Na+ 4 Time (ms) K+ \u278a R\u0007 esting membrane potential: membrane is more permeable to K+ than Na+ at rest. Voltage-gated Na+ and K+ channels are closed. \u278b M\u0007 embrane depolarization: Na+ activation gate opens \u008e\u00a0Na+ flows inward. \u278c \u0007Membrane repolarization: Na+ inactivation gate closes at peak potential, thus stopping Na+ inflow. K+ activation gate opens \u008e\u00a0K+ flows outward. \u278d M\u0007 embrane hyperpolarization: K+ activation gates are slow to close \u008e\u00a0excess K+ efflux and brief period of hyperpolarization. Voltage-gated Na+ channels switch back to resting state. Na+\/K+ pump restores ions concentration. Sensory receptors SENSORY NEURON FIBER TYPE LOCATION SENSES RECEPTOR TYPE A\u03b4\u2014fast, myelinated fibers All tissues except cartilage and Pain, temperature C\u2014slow, unmyelinated eye lens; numerous in skin Free nerve endings A Delta plane is fast, but a Dynamic, fine\/light touch, Glabrous (hairless) skin low-frequency vibration, skin Meissner corpuscles taxC is slow indentation Deep skin layers, ligaments, Pacinian corpuscles Large, myelinated fibers; adapt joints High-frequency vibration, Merkel discs quickly pressure Ruffini corpuscles Finger tips, superficial skin Large, myelinated fibers; adapt Pressure, deep static touch (eg, quickly Finger tips, joints shapes, edges) Large, myelinated fibers; adapt Stretch, joint angle change slowly Large, myelinated fiber intertwined among collagen fiber bundles; adapt slowly uploaded by medbooksvn","506 SEC TION III Neurology and Special Senses\u2003 \uf07d\u2009neurology\u2014Anatomy and Physiology Peripheral nerve Endoneurium\u2014thin, supportive connective Endo = inner tissue that ensheathes and supports individual Peri = around Nerve trunk myelinated nerve fibers. May be affected in Epi = outer Epineurium Guillain-Barr\u00e9 syndrome. Perineurium Endoneurium Perineurium (blood-nerve permeability barrier)\u2014surrounds a fascicle of nerve fibers. Nerve \ufb01ber Epineurium\u2014dense connective tissue that surrounds entire nerve (fascicles and blood vessels). Chromatolysis Reaction of neuronal cell body to axonal injury. Changes reflect \u008f protein synthesis in effort to repair the damaged axon. Characterized by: \u0083\t Round cellular swelling \u0083\t Displacement of the nucleus to the periphery \u0083\t Dispersion of Nissl substance throughout cytoplasm Wallerian degeneration\u2014disintegration of the axon and myelin sheath distal to site of axonal injury with macrophages removing debris. Proximal to the injury, the axon retracts, and the cell body sprouts new protrusions that grow toward other neurons for potential reinnervation. Serves as a preparation for axonal regeneration and functional recovery. Round cellular Site of damage Myelin Microglia swelling debris in\ufb01ltration Displacement of nucleus to periphery Dispersion of Nissl substance Chromatolysis Axonal retraction Wallerian degeneration Injured neuron Neurotransmitter changes with disease LOCATION OF ANXIETY DEPRESSION SCHIZOPHRENIA ALZHEIMER HUNTINGTON PARKINSON SYNTHESIS DISEASE DISEASE DISEASE Acetylcholine \u0090 Basal nucleus \u008f \u0090 \u0090 \u008f of Meynert \u0090 (forebrain) Dopamine Ventral \u0090\u008f \u008f\u0090 tegmentum, SNc (midbrain) GABA Nucleus \u0090 accumbens (basal ganglia) Norepinephrine Locus ceruleus \u0090 (pons) \u0090\u0090 Serotonin Raphe nuclei (brainstem)","Neurology and Special Senses\u2003 \uf07d\u2009neurology\u2014Anatomy and Physiology SEC TION III 507 Meninges Three membranes that surround and protect CSF flows in the subarachnoid space, located the brain and spinal cord. Derived from both between arachnoid and pia mater. Dura mater Bridging veins neural crest and mesoderm: \u0083\t Dura mater\u2014thick outer layer closest to Epidural space\u2014potential space between dura Arachnoid skull. mater and skull\/vertebral column containing mater \u0083\t Arachnoid mater\u2014middle layer, contains fat and blood vessels. Site of blood collection weblike connections. associated with middle meningeal artery Pia mater \u0083\t Pia mater\u2014thin, fibrous inner layer that injury. firmly adheres to brain and spinal cord. Brain Blood-brain barrier Prevents circulating blood substances Circumventricular organs with fenestrated capillaries and no blood-brain barrier Astrocyte foot (eg,\u00a0bacteria, drugs) from reaching the CSF\/ allow molecules in blood to affect brain processes CNS. Formed by 4 structures: function (eg, area postrema\u2014vomiting after chemotherapy; OVLT [organum vasculosum Capillary \u0083\t Tight junctions between nonfenestrated lamina terminalis]\u2014osmoreceptors) or lumen capillary endothelial cells neurosecretory products to enter circulation (eg, neurohypophysis\u2014ADH release). Tight Basement \u0083\t Basement membrane junction membrane \u0083\t Pericytes BBB disruption (eg, stroke) \u008e vasogenic edema. Hyperosmolar agents (eg, mannitol) can disrupt \u0083\t Astrocyte foot processes the BBB \u008e\u00a0\u008f\u00a0permeability of medications. Glucose and amino acids cross slowly by carrier- mediated transport mechanisms. Nonpolar\/lipid-soluble substances cross rapidly via diffusion. Vomiting center Coordinated by NTS in the medulla, which receives information from the chemoreceptor trigger zone (CTZ, located within area postrema (pronounce \u201cpuke\u201d-strema) in 4th ventricle), GI tract (via vagus nerve), vestibular system, and CNS. CTZ and adjacent vomiting center nuclei receive input through 5 major receptors: histamine (H1), muscarinic (M1), neurokinin (NK-1), dopamine (D2), and serotonin (5-HT3). \u0083\t 5-HT3, D2, and NK-1 antagonists treat chemotherapy-induced vomiting. \u0083\t H1 and M1 antagonists treat motion sickness; H1 antagonists treat hyperemesis gravidarum. uploaded by medbooksvn","508 SEC TION III Neurology and Special Senses\u2003 \uf07d\u2009neurology\u2014Anatomy and Physiology Sleep physiology Sleep cycle is regulated by the circadian rhythm, which is driven by suprachiasmatic nucleus (SCN) of the hypothalamus. Circadian rhythm controls nocturnal release of ACTH, prolactin, melatonin, SLEEP STAGE (% OF TOTAL SLEEP norepinephrine: SCN \u008e\u00a0norepinephrine release \u008e\u00a0pineal gland \u008e\u00a0\u008f\u00a0melatonin. SCN is regulated TIME IN YOUNG ADULTS) by environment (eg, light). Awake (eyes open) Two stages: rapid-eye movement (REM) and non-REM. Awake (eyes closed) Alcohol, benzodiazepines, and barbiturates are associated with \u0090 REM sleep and N3 sleep; Non-REM sleep norepinephrine also \u0090 REM sleep. Stage N1 (5%) Benzodiazepines are useful for night terrors and sleepwalking by \u0090\u00a0N3 and REM sleep. Stage N2 (45%) Stage N3 (25%) DESCRIPTION EEG WAVEFORM AND NOTES REM sleep (25%) Alert, active mental concentration. Beta (highest frequency, lowest amplitude). Alpha. Light sleep. Theta. Sleep spindles and K complexes. Deeper sleep; when bruxism (\u201ctwoth\u201d [tooth] grinding) occurs. Delta (lowest frequency, highest amplitude), deepest sleep stage. Deepest non-REM sleep (slow-wave sleep); sleepwalking, night terrors, and bedwetting Beta. occur (wee and flee in N3). Changes in older adults: \u0090\u00a0REM, \u0090\u00a0N3, \u008f\u00a0sleep Loss of motor tone, \u008f\u00a0brain O2 use, variable latency, \u008f\u00a0early awakenings. pulse\/BP, \u008f\u00a0ACh. REM is when dreaming, Changes in depression: \u008f\u00a0REM sleep time, nightmares, and penile\/clitoral tumescence occur; may serve memory processing function. \u0090\u00a0REM latency, \u0090\u00a0N3, repeated nighttime awakenings, early morning awakening (terminal Extraocular movements due to activity of PPRF insomnia). (paramedian pontine reticular formation\/ Change in narcolepsy: \u0090\u00a0REM latency. conjugate gaze center). At night, BATS Drink Blood. Occurs every 90 minutes, and duration \u008f\u00a0through the night.","Neurology and Special Senses\u2003 \uf07d\u2009neurology\u2014Anatomy and Physiology SEC TION III 509 Hypothalamus Maintains homeostasis by regulating Thirst and water balance, controlling Adenohypophysis (anterior pituitary) and Neurohypophysis (posterior pituitary) release of hormones produced in Lateral nucleus the hypothalamus, and regulating Hunger, Autonomic nervous system, Temperature, and Sexual Ventromedial nucleus urges (TAN HATS). Anterior nucleus Inputs (areas not protected by blood-brain barrier): OVLT (senses change in osmolarity), area Posterior nucleus postrema (found in dorsal medulla, responds to emetics). Suprachiasmatic nucleus Hunger. Stimulated by ghrelin, inhibited by Lateral injury makes you lean. Supraoptic and leptin. Destruction \u008e anorexia, failure to thrive (infants). paraventricular nuclei Satiety. Stimulated by leptin. Ventromedial injury makes you very massive. Destruction (eg, craniopharyngioma) Preoptic nucleus \u008e\u00a0hyperphagia. Cooling, parasympathetic. A\/C = Anterior Cooling. Heating, sympathetic. Heating controlled by posterior nucleus (\u201chot\u00a0pot\u201d). Circadian rhythm. SCN is a Sun-Censing Nucleus. Synthesize ADH and oxytocin. SAD POX: Supraoptic = ADH, Paraventricular = OXytocin. Thermoregulation, sexual behavior. Releases GnRH. ADH and oxytocin are carried by neurophysins down axons to posterior pituitary, where these hormones are stored and released. Failure of GnRH-producing neurons to migrate from olfactory pit \u008e\u00a0Kallmann syndrome. Thalamus Major relay for all ascending sensory information except olfaction. NUCLEI INPUT SENSES DESTINATION MNEMONIC Ventral postero\u00adlateral Spinothalamic and Vibration, pain, pressure, 1\u00b0 somatosensory Very pretty nucleus dorsal columns\/medial proprioception cortex (parietal makeup goes on lemniscus (conscious), light touch, lobe) the face Ventral postero\u00ad temperature medial nucleus Lateral = light Trigeminal and gustatory Face sensation, taste 1\u00b0 somatosensory (vision) Lateral geniculate pathway cortex (parietal nucleus lobe) Medial = music Medial geniculate (hearing) nucleus CN II, optic chiasm, optic Vision 1\u00b0 visual cortex Ventral anterior and tract (occipital lobe) Venus astronauts ventral lateral nuclei vow to love Superior olive and inferior Hearing 1\u00b0 auditory cortex moving colliculus of tectum (temporal lobe) Basal ganglia, cerebellum Motor Motor cortices (frontal lobe) uploaded by medbooksvn","510 SEC TION III Neurology and Special Senses\u2003 \uf07d\u2009neurology\u2014Anatomy and Physiology Limbic system Collection of neural structures involved in The famous 5 F\u2019s. A emotion, long-term memory, olfaction, behavior modulation, ANS function. Consists of hippocampus (red arrows in A ), amygdalae, mammillary bodies, anterior thalamic nuclei, cingulate gyrus (yellow arrows in A ), entorhinal cortex. Responsible for feeding, fleeing, fighting, feeling, and sex. Dopaminergic Commonly altered by drugs (eg, antipsychotics) and movement disorders (eg, Parkinson disease). pathways The mesocortical and mesolimbic pathways are involved in addiction behaviors. PATHWAY PROJECTION FUNCTION SYMPTOMS OF ALTERED ACTIVITY NOTES Mesocortical Ventral tegmental area Motivation and reward \u0090\u00a0activity \u008e\u00a0negative Antipsychotics have \u008e\u00a0prefrontal cortex symptoms limited effect Mesolimbic Ventral tegmental \u008f\u00a0activity \u008e\u00a0positive 1\u00b0 therapeutic target of Nigrostriatal area \u008e\u00a0nucleus symptoms antipsychotics accumbens Tuberoinfundibular Substantia nigra Motor control \u0090\u00a0activity Significantly affected \u008e\u00a0dorsal striatum (pronounce \u008e\u00a0extrapyramidal by antipsychotics and \u201cnigrostrideatal\u201d) symptoms in Parkinson disease Hypothalamus Regulation of \u0090\u00a0activity Significantly affected \u008e\u00a0pituitary prolactin secretion \u008e\u00a0\u008f\u00a0prolactin by antipsychotics Dorsal striatum Substantia nigra Hypothalamus Mesocortical pathway Nucleus accumbens Mesolimbic pathway Nigrostriatal pathway Pituitary gland Tuberoinfundibular pathway Ventral tegmental area","Neurology and Special Senses\u2003 \uf07d\u2009neurology\u2014Anatomy and Physiology SEC TION III 511 Cerebellum Modulates movement; aids in coordination and Medial cerebellum (eg, vermis) controls axial A balance A . and proximal limb musculature bilaterally \u0083\t Ipsilateral (unconscious) proprioceptive (medial structures). information via inferior cerebellar peduncle from spinal cord Lateral cerebellum (ie, hemisphere) controls \u0083\t Deep nuclei (lateral \u008e medial)\u2014dentate, distal limb musculature ipsilaterally (lateral emboliform, globose, fastigial (don\u2019t eat structures). greasy foods) Tests: rapid alternating movements (pronation\/ supination), finger-to-nose, heel-to-shin, gait, look for intention tremor. Cerebellar input Cerebellar output Contralateral Middle Deep nuclei Superior Contralateral cortex cerebellar cerebellar cortex peduncle Cerebellar cortex peduncle via Purkinje cells Proprioceptive Spinal Inferior information cord cerebellar peduncle Inner ear Vestibular nuclei Vestibular nuclei Flocculonodular Lateral Medial lobe cerebellum cerebellum uploaded by medbooksvn","512 SEC TION III Neurology and Special Senses\u2003 \uf07d\u2009neurology\u2014Anatomy and Physiology Basal ganglia Important in voluntary movements and adjusting posture A . D1 Receptor = D1Rect A Receives cortical input, provides negative feedback to cortex to pathway. C modulate movement. Indirect (D2) = Inhibitory. L Striatum = putamen (motor) + Caudate nucleus (cognitive). Lentiform nucleus = putamen + globus pallidus. T Direct (excitatory) pathway\u2014cortical input (via glutamate) stimulates GABA release from the striatum, which inhibits GABA release from GPi, disinhibiting (activating) the Thalamus \u008e \u008f motion. Indirect (inhibitory) pathway\u2014cortical input (via glutamate) stimulates GABA release from the striatum, which inhibits GABA release from GPe, disinhibiting (activating) the STN. STN input (via glutamate) stimulates GABA release from GPi, inhibiting the Thalamus \u008e \u0090 motion. Dopamine from SNc (nigrostriatal pathway) stimulates the direct pathway (by binding to D1 receptor) and inhibits the indirect pathway (by binding to D2 receptor) \u008e \u008f motion. Input from SNc Dopamine D1 D2 Frontal plane through brain Direct Indirect Posterior Anterior pathway pathway Motor cortex facilitates inhibits Lateral ventricle Third ventricle Thalamus movement movement Caudate nucleus Thalamus STN Internal capsule Hypothalamus Subthalamic From Striatum Lentiform Putamen nucleus (STN) SNc nucleus Globus pallidus Substantia Direct (GPe\/GPi) nigra (SNc) GPi GPe Indirect Insula Amygdala Mammillary body Hippocampus Spinal Stimulatory cord Inhibitory","Neurology and Special Senses\u2003 \uf07d\u2009neurology\u2014Anatomy and Physiology SEC TION III 513 Cerebral cortex regions Premotor Central sulcus Somatosensory cortex association cortex Frontal eye Primary motor \ufb01eld somPartiomsaernysory Frontal Parietal Prefrontal lobe lobe cortex Arcuate fasciculus Broca area Temporal Occipital Wernicke area Sylvian \ufb01ssure lobe lobe Primary Limbic visual cortex association area Primary auditory cortex Cerebral perfusion Relies on tight autoregulation. Primarily driven Therapeutic hyperventilation \u008e\u00a0\u0090\u00a0Pco2 by Pco2 (Po2 also modulates perfusion in \u008e\u00a0vasoconstriction \u008e\u00a0\u0090\u00a0cerebral blood flow severe hypoxia). Cerebral blood \ufb02ow (mL\/100g\/min) \u008e\u00a0\u0090\u00a0ICP. May be used to treat acute cerebral edema (eg, 2\u00b0 to stroke) unresponsive to other Also relies on a pressure gradient between interventions. mean arterial pressure (MAP) and intracranial pressure (ICP). \u0090\u00a0blood pressure or \u008f\u00a0ICP CPP = MAP \u2013 ICP. If CPP = 0, there is no \u008e\u00a0\u0090\u00a0cerebral perfusion pressure (CPP). cerebral perfusion \u008e\u00a0brain death (coma, absent brainstem reflexes, apnea). Cushing reflex\u2014triad of hypertension, bradycardia, and respiratory depression in Hypoxemia increases CPP only if Po2 response to \u008f ICP. <\u00a050\u00a0mm\u00a0Hg. 100 CPP is directly proportional to Pco2 until Pco2 > 90 mm Hg. PaO\u2082 PaCO\u2082 75 MAP 50 25 0 0 50 100 150 200 Pressure (mm Hg) uploaded by medbooksvn","514 SEC TION III Neurology and Special Senses\u2003 \uf07d\u2009neurology\u2014Anatomy and Physiology Homunculus Topographic representation of motor and sensory areas in the cerebral cortex. Distorted appearance is due to certain body regions being more richly innervated and thus having \u008f\u00a0cortical representation. Motor homunculus Sensory homunculus Anterior Hip Knee Leg Hip cerebral Trunk Ankle Trunk artery Foot FoWrrieEsSlatrhboomAurwlHdNmeeearcdk Middle SEhlobWuolwrdiset r Toes Toes cerebral NTehIncMudkmiRedixbLdnilgteHtleand Fingers Genitals LiRtMtilTniIednghdduleemx b artery Brow Fingers Eye Posterior Eyelid & eyeball Nose cerebral Lips Face artery Jaw Tongue Upper lip Swallowing Lower lip Teeth, gums IntPrah-aarbyndxominal Tongue Cerebral arteries\u2014cortical distribution Anterior Anterior cerebral artery (supplies anteromedial surface) Middle cerebral artery (supplies lateral surface) Posterior cerebral artery (supplies posterior and inferior surfaces) Anterior Posterior Watershed zones Cortical border zones occur between anterior Posterior A and middle cerebral arteries and posterior and middle cerebral arteries (blue areas in A ). Common locations for brain metastases. Infarct due to severe hypoperfusion: Internal border zones occur between the superficial and deep vascular territories of the \u0083\t ACA-MCA watershed infarct\u2014proximal middle cerebral artery (red areas in A ). upper and lower extremity weakness (\u201cman- in-a-barrel syndrome\u201d). \u0083\t PCA-MCA watershed infarct\u2014higher-order visual dysfunction.","Neurology and Special Senses\u2003 \uf07d\u2009neurology\u2014Anatomy and Physiology SEC TION III 515 Circle of Willis System of anastomoses between anterior and posterior blood supplies to brain. Anterior ACom Anterior Optic chiasm circulation communicating ACA ACA Anterior A2 Internal carotid ICA ICA cerebral A1 Lenticulo- MCA striate Posterior MCA Middle ACA circulation cerebral MCA PCA INFERIOR VIEW M1 OF PCom Posterior Anterior BA communicating P1 choroidal PCom ICA Posterior P2 ECA cerebral PCA SCA Superior Pontine CCA VA cerebellar Brachio- cephalic Sub- clavian AICA Anterior inferior Basilar BA Aorta cerebellar PICA Posterior inferior Vertebral VA OBLIQUE-LATERAL VIEW cerebellar Anterior spinal ASA Dural venous sinuses Large venous channels A that run through the periosteal and meningeal layers of the dura mater. A Drain blood from cerebral veins (arrow) and receive CSF from arachnoid granulations. Empty into internal jugular vein. Venous sinus thrombosis\u2014presents with signs\/symptoms of \u008f\u00a0ICP (eg, headache, seizures, papilledema, focal neurologic deficits). May lead to venous hemorrhage. Associated with hypercoagulable states (eg, pregnancy, OCP use, factor V Leiden). Superior sagittal sinus Superior ophthalmic vein (main location of CSF return Sphenoparietal sinus via arachnoid granulations) Cavernous sinus Inferior sagittal sinus Sigmoid sinus Great cerebral vein of Galen Jugular foramen Internal jugular vein Straight sinus Con\ufb02uence of the sinuses Occipital sinus Transverse sinus uploaded by medbooksvn","516 SEC TION III Neurology and Special Senses\u2003 \uf07d\u2009neurology\u2014Anatomy and Physiology Ventricular system Lateral ventricles \u008e 3rd ventricle via right and left interventricular foramina of Monro. Lateral ventricles Posterior horn 3rd ventricle \u008e 4th ventricle via cerebral Anterior aqueduct of Sylvius. horn Inferior horn 4th ventricle \u008e subarachnoid space via: Interventricular \u0083\t Foramina of Luschka = lateral. foramina Foramina of \u0083\t Foramen of Magendie = medial. of Monro Luschka\/ lateral CSF made by choroid plexuses located in the Inferior Third ventricle aperture lateral, third, and fourth ventricles. Travels to horn subarachnoid space via foramina of Luschka Cerebral aqueduct Foramen of and Magendie, is reabsorbed by arachnoid Foramina of of Sylvius Magendie\/medial granulations, and then drains into dural venous Luschka\/lateral aperture sinuses. Fourth ventricle aperture Central canal of spinal cord Brainstem\u2014ventral view Olfactory bulb 4 CN are above pons (I, II, III, IV). (CN I) 4 CN exit the pons (V, VI, VII, VIII). Optic chiasm 4 CN are in medulla (IX, X, XI, XII). Olfactory tract 4 CN nuclei are medial (III, IV, VI, XII). Infundibulum CN II \u201cFactors of 12, except 1 and 2.\u201d Mammillary body Optic tract Pons Middle cerebellar CN III peduncle CN IV Pyramid (arises dorsally Pyramidal and immediately decussation decussates) C1 CN V CN VI CN VII CN VIII CN IX Exit the midbrain CN X Exit at the pons CN XI Exit in the medulla CN XII Brainstem\u2014dorsal view (cerebellum removed) Pineal gland\u2014melatonin secretion, circadian rhythms. Third ventricle Superior colliculi\u2014direct eye movements Pineal gland Thalamus to stimuli (noise\/movements) or objects of interest. Anterior wall of Superior colliculus fourth ventricle Inferior colliculus Inferior colliculi\u2014auditory. Your eyes are above your ears, and the superior Superior cerebellar peduncle colliculus (visual) is above the inferior colliculus (auditory). Middle cerebellar peduncle Inferior cerebellar peduncle Medulla","Neurology and Special Senses\u2003 \uf07d\u2009neurology\u2014Anatomy and Physiology SEC TION III 517 Cranial nerve nuclei Located in tegmentum portion of brainstem Lateral nuclei = sensory (alar plate). (between dorsal and ventral portions): \u2014Sulcus limitans\u2014 \u0083\t Midbrain\u2014nuclei of CN III, IV Medial nuclei = motor (basal plate). \u0083\t Pons\u2014nuclei of CN V, VI, VII, VIII \u0083\t Medulla\u2014nuclei of CN IX, X, XII \u0083\t Spinal cord\u2014nucleus of CN XI Vagal nuclei FUNCTION CRANIAL NERVES NUCLEUS Visceral sensory information (eg, taste, VII, IX, X baroreceptors, gut distention) Nucleus tractus IX, X solitarius May play a role in vomiting X Nucleus ambiguus Motor innervation of pharynx, larynx, upper esophagus (eg, swallowing, palate elevation) Dorsal motor nucleus Sends autonomic (parasympathetic) fibers to heart, lungs, upper GI uploaded by medbooksvn","518 SEC TION III Neurology and Special Senses\u2003 \uf07d\u2009neurology\u2014Anatomy and Physiology Brainstem cross sections Medial Midbrain lemniscus Superior Red colliculus nucleus Cerebral Substantia aqueduct nigra Crus CN III cerebri nucleus CN III \ufb01bers Pons Fourth Superior ventricle cerebellar peduncle Medial Locus longitudinal ceruleus fasciculus Medial Middle lemniscus cerebellar peduncle CN V Corticospinal and corticobulbar tracts","Neurology and Special Senses\u2003 \uf07d\u2009neurology\u2014Anatomy and Physiology SEC TION III 519 Brainstem cross sections (continued) CN XII nucleus Medulla Dorsal motor nucleus Nucleus tractus solitarius Inferior cerebellar CN X peduncle Medial lemniscus Medial longitudinal fasciculus Nucleus ambiguus Inferior olivary nucleus Pyramid uploaded by medbooksvn","520 SEC TION III Neurology and Special Senses\u2003 \uf07d\u2009neurology\u2014Anatomy and Physiology Cranial nerves and vessel pathways Anterior Cribriform plate CN I cranial fossa (through CN II ethmoid bone) Ophthalmic artery CN III Optic canal CN IV CN VI Middle cranial fossa Superior orbital \ufb01ssure CN V1 CN V2 (through CN V3 Middle meningeal artery sphenoid bone) CN VII CN VIII Foramen rotundum CN IX Foramen ovale CN X Foramen spinosum CN XI Jugular vein Internal auditory meatus CN XII Brainstem Posterior Jugular foramen Spinal root of CN XI cranial fossa Hypoglossal canal Vertebral arteries (through temporal or Anterior cerebral (ACA) occipital bone) Anterior communicating Ophthalmic artery Foramen magnum Middle cerebral (MCA) Internal carotid Cranial nerves and arteries Anterior choroidal Posterior communicating Midbrain Medial I Posterior cerebral (PCA) Lateral II Superior cerebellar Pons Medial III IV Basilar Lateral V Labyrinthine VI Anterior inferior cerebellar VII VIII Vertebral Posterior inferior cerebellar Medulla Lateral IX X Anterior spinal Arteries XI Medial XII Cranial nerves","Neurology and Special Senses\u2003 \uf07d\u2009neurology\u2014Anatomy and Physiology SEC TION III 521 Cranial nerves CN FUNCTION TYPE MNEMONIC NERVE I Smell (only CN without thalamic relay to cortex) Sensory Some Say Olfactory II Sight Sensory Marry Optic Oculomotor III Eye movement (SR, IR, MR, IO), pupillary constriction (sphincter Motor Money pupillae), accommodation (ciliary muscle), eyelid opening (levator But Trochlear palpebrae) Trigeminal My IV Eye movement (SO) Motor Brother Abducens Facial V Mastication, facial sensation (ophthalmic, maxillary, mandibular Both Says Big Vestibulocochlear divisions), somatosensation from anterior 2\/3 of tongue, Glossopharyngeal dampening of loud noises (tensor tympani) Brains Vagus VI Eye movement (LR) Motor Matter Most Accessory VII Facial movement, eye closing (orbicularis oculi), auditory volume Both Hypoglossal modulation (stapedius), taste from anterior 2\/3 of tongue (chorda tympani), lacrimation, salivation (submandibular and sublingual glands are innervated by CN seven) VIII Hearing, balance Sensory IX Taste and sensation from posterior 1\/3 of tongue, swallowing, Both salivation (parotid gland), monitoring carotid body and sinus chemo- and baroreceptors, and elevation of pharynx\/larynx (stylopharyngeus) X Taste from supraglottic region, swallowing, soft palate elevation, Both midline uvula, talking, cough reflex, parasympathetics to thoracoabdominal viscera, monitoring aortic arch chemo- and baroreceptors XI Head turning, shoulder shrugging (SCM, trapezius) Motor XII Tongue movement Motor Cranial nerve refl xes AFFERENT EFFERENT REFLEX II III V1 ophthalmic (nasociliary branch) Bilateral VII (temporal and zygomatic Accommodation Corneal branches\u2014orbicularis oculi) X (also phrenic and spinal nerves) Cough X X Gag IX V3 (motor\u2014masseter) Jaw jerk V3 (sensory\u2014muscle spindle from masseter) VII Lacrimation V1 (loss of reflex does not preclude emotional III Pupillary tears) II uploaded by medbooksvn","522 SEC TION III Neurology and Special Senses\u2003 \uf07d\u2009neurology\u2014Anatomy and Physiology Mastication muscles 3 muscles close jaw: masseter, temporalis, medial pterygoid (M\u2019s munch). Temporalis Lateral pterygoid protrudes jaw. Masseter All are innervated by mandibular branch of Lateral trigeminal nerve (CN V3). pterygoid Medial pterygoid Spinal nerves There are 31 pairs of spinal nerves: 8 cervical, 12\u00a0thoracic, 5 lumbar, 5 sacral, 1\u00a0coccygeal. Nerves C1\u2013C7 exit above the corresponding vertebrae (eg, C3 exits above the 3rd cervical vertebra). C8 spinal nerve exits below C7 and above T1. All other nerves exit below (eg, L2 exits below the 2nd lumbar vertebra). Spinal cord\u2014lower In adults, spinal cord ends at lower border of Anterior extent L1\u2013L2 vertebrae. Subarachnoid space (which longitudinal contains the CSF) extends to lower border ligament of S2 vertebra. Lumbar puncture is usually Q L1 Posterior performed between L3\u2013L4 or L4\u2013L5 (level of R cauda equina) to obtain sample of CSF while longitudinal avoiding spinal cord. To keep the cord alive, S ligament keep the spinal needle between L3 and L5. T U Conus Needle passes through: V medullaris \u2002Skin W \u2002 Fascia and fat X Cauda \u2002 Supraspinous ligament Y equina \u2002 Interspinous ligament Needle \u2002 Ligamentum flavum S1 \u2002\u0007Epidural space Filum terminale (epidural anesthesia needle stops here) \u2002 Dura mater \u2002 Arachnoid mater \u2002\u0007Subarachnoid space (CSF\u00a0collection occurs here)","Neurology and Special Senses\u2003 \uf07d\u2009neurology\u2014Anatomy and Physiology SEC TION III 523 \u00adS\u00ad pinal cord and Legs (lumbosacral) are lateral in lateral corticospinal, spinothalamic tracts. associated tracts Dorsal columns are organized as you are, with hands at sides. \u201cArms outside, legs inside.\u201d Central canal ASCENDING Dorsal column Posterior horn Sacral (pressure, vibration, \ufb01ne touch, [conscious] Lumbar proprioception) DESCENDING Thoracic \u2022 Fasciculus graciLis (Lower body, legs) Lateral corticospinal tract Cervical \u2022 Fasciculus cUneatus (Upper body, arms) (voluntary motor) Gray matter \u2022 Sacral Intermediate horn (sympathetic) \u2022 Cervical (T1 - L2\/L3) Anterior corticospinal tract ASCENDING (voluntary motor) Lateral spinothalamic tract (pain, temperature) \u2022 Sacral White matter \u2022 Cervical Anterior horn Anterior spinothalamic tract (crude touch, pressure) uploaded by medbooksvn","524 SEC TION III Neurology and Special Senses\u2003 \uf07d\u2009neurology\u2014Anatomy and Physiology Spinal tract anatomy Spinothalamic tract and dorsal column (ascending tracts) synapse and then cross. and functions Corticospinal tract (descending tract) crosses and then synapses. FUNCTION Spinothalamic tract Dorsal column Corticospinal tract 1ST-ORDER NEURON Pain, temperature Pressure, vibration, fine touch, Voluntary movement 1ST SYNAPSE proprioception (conscious) 2ND-ORDER NEURON Sensory nerve ending (A\u03b4 and Sensory nerve ending of UMN: 1\u00b0 motor cortex \u008e 2ND SYNAPSE C fibers) of pseudounipolar pseudounipolar neuron descends ipsilaterally 3RD-ORDER NEURON neuron in dorsal root in dorsal root ganglion \u008e (through posterior limb of ganglion \u008e enters spinal cord enters spinal cord \u008e ascends internal capsule and cerebral ipsilaterally in dorsal columns peduncle), decussates at caudal medulla (pyramidal decussation) \u008e descends contralaterally Posterior horn (spinal cord) Nucleus gracilis, nucleus Anterior horn (spinal cord) cuneatus (ipsilateral medulla) Decussates in spinal cord Decussates in medulla \u008e LMN: leaves spinal cord as the anterior white ascends contralaterally as the commissure \u008e ascends medial lemniscus contralaterally VPL (thalamus) VPL (thalamus) NMJ (skeletal muscle) Projects to 1\u00b0 somatosensory Projects to 1\u00b0 somatosensory cortex cortex Primary Primary somatosensory motor cortex cortex Thalamus Dorsal column Internal Medulla nuclei capsule Decussation of Anterior white medial lemniscus Cerebral commissure peduncle First-order neuron Second-order neuron Medulla Third-order neuron Pyramidal decussation Anterior horn NMJ","Neurology and Special Senses\u2003 \uf07d\u2009neurology\u2014Anatomy and Physiology SEC TION III 525 Clinical refl xes Reflexes count up in order (main nerve root in Additional reflexes: bold): Cremasteric reflex = L1, L2 (\u201ctesticles move\u201d) C5, 6 Achilles reflex = S1, S2 (\u201cbuckle my shoe\u201d) Anal wink reflex = S3, S4 (\u201cwinks galore\u201d) C6, 7, 8 Patellar reflex = L2-L4 (\u201ckick the door\u201d) L2, 3, 4 Biceps and brachioradialis reflexes = C5, C6 Reflex grading: S1, 2 (\u201cpick up sticks\u201d) 0: absent Triceps reflex = C6, C7, C8 (\u201clay them 1+: hypoactive straight\u201d) 2+: normal 3+: hyperactive 4+: clonus Primitive refl xes CNS reflexes that are present in a healthy infant, but are absent in a neurologically intact adult. Normally disappear within 1st year of life. These primitive reflexes are inhibited by a mature\/ \u0007Moro reflex \u0007Rooting reflex developing frontal lobe. They may reemerge in adults following frontal lobe lesions \u008e loss of \u0007Sucking reflex inhibition of these reflexes. P\u0007 almar reflex Plantar reflex \u201cHang on for life\u201d reflex\u2014abduct\/extend arms when startled, and then draw together. G\u0007 alant reflex Movement of head toward one side if cheek or mouth is stroked (nipple seeking). Sucking response when roof of mouth is touched. Curling of fingers if palm is stroked. Dorsiflexion of large toe and fanning of other toes with plantar stimulation. Babinski sign\u2014presence of this reflex in an adult, which may signify a UMN lesion. Stroking along one side of the spine while newborn is in ventral suspension (face down) causes lateral flexion of lower body toward stimulated side. Landmark dermatomes DERMATOME CHARACTERISTICS V1 C2 C2 Posterior half of skull V2 C2 C6 C6 C8 C3 C3 V3 C5 C7 C4 High turtleneck shirt C3 C5 C4 Diaphragm and gallbladder pain referred C6 C7 C8 C6 C4 C8 C7 to the right shoulder via phrenic nerve C5 C8 C3, 4, 5 keeps the diaphragm alive T1 T1 T2 T2 Low-collar shirt T3 T3 T4 T4 C6 Includes thumbs T5 T5 T4 Thumbs up sign on left hand looks like a 6 T6 T6 T7 T7 T7 T10 At the nipple T8 T8 L1 T4 at the teat pore T9 L4 T9 T10 S2, S3, S4 At the xiphoid process T10 T11 7 letters in xiphoid T12 T11 L1 At the umbilicus (belly butten) L2 Point of referred pain in early appendicitis T12 L1 L3 L4 At the Inguinal Ligament L2 L5 L3 S1 Includes the kneecaps S2 S3 Down on ALL 4\u2019s S4 S5 Sensation of penile and anal zones S2, 3, 4 keep the penis off the floor S2 S3 L5 S1 S2 L4 L1 L2 L5 L3 S1 S2 S1 L4 L4 S1 L5 L5 L4 uploaded by medbooksvn","526 SEC TION III Neurology and Special Senses\u2003 \uf07d\u2009neurology\u2014Pathology ` \u2009NEUROLOGY \u2014 PATHOLOGY Common brain lesions COMPLICATIONS AREA OF LESION Frontal lobe syndrome\u2014disinhibition, hyperphagia, impulsivity, loss of empathy, impaired executive function, akinetic mutism. Seen in frontotemporal dementia. Prefrontal cortex Eyes look toward brain lesion (ie, away from side of hemiplegia). Seen in MCA stroke. Frontal eye fields Eyes look away from brain lesion (ie, toward side of hemiplegia). Paramedian pontine reticular formation Gerstmann syndrome\u2014agraphia, acalculia, finger agnosia, left-right disorientation. Dominant parietal cortex Hemispatial neglect syndrome\u2014agnosia of the contralateral side of the world. Nondominant parietal cortex Tremor at rest, chorea, athetosis. Seen in Parkinson disease, Huntington disease. Basal ganglia Contralateral hemiballismus. Subthalamic nucleus Bilateral lesions \u008e\u00a0Wernicke-Korsakoff syndrome (due to thiamine deficiency). Mammillary bodies Bilateral lesions \u008e\u00a0Kl\u00fcver-Bucy syndrome\u2014disinhibition (eg, hyperphagia, hypersexuality, Amygdala hyperorality). Seen in HSV-1 encephalitis. Hippocampus Bilateral lesions \u008e\u00a0anterograde amnesia (no new memory formation). Seen in Alzheimer disease. Dorsal midbrain Parinaud syndrome (often due to pineal gland tumors). Reticular activating Reduced levels of arousal and wakefulness, coma. system Medial longitudinal Internuclear ophthalmoplegia (impaired adduction of ipsilateral eye; nystagmus of contralateral eye fasciculus with abduction). Seen in multiple sclerosis. Cerebellar hemisphere Intention tremor, limb ataxia, loss of balance; damage to cerebellum \u008e\u00a0ipsilateral deficits; fall Cerebellar vermis toward side of lesion. Cerebellar hemispheres are laterally located\u2014affect lateral limbs. Truncal ataxia (wide-based, \u201cdrunken sailor\u201d gait), nystagmus, dysarthria. Degeneration associated with chronic alcohol overuse. Vermis is centrally located\u2014affects central body. Abnormal motor posturing Decorticate (flexor) posturing Decerebrate (extensor) posturing SITE OF LESION Above red nucleus (often cerebral cortex) Between red and vestibular nuclei (brainstem) OVERACTIVE TRACTS Rubrospinal and vestibulospinal tracts Vestibulospinal tract PRESENTATION Upper limb flexion, lower limb extension Upper and lower limb extension (abo(avteLoErreSbdIOeNnlNLOouETcwSEleISrOuesdN) nucleus) (at or belLoEwSIrOedN\u201cnYucoleuurs)hDaencodrtsicaatreepnosetuarrintghe coDre(choretiacratte)\u201dpDosetcuerrinebgrate posturWingorse pDreocegrneborsaites posturing rebRreadl cnourctleexus Red Rnubcrleousps inal tract Rubrospinal tract Vestibular nucleus Flexors Flexors VestibVuelastribnuulcolespuisnal tract Vestibulospinal tract Extensors Extensors","Neurology and Special Senses\u2003 \uf07d\u2009neurology\u2014Pathology SEC TION III 527 Ischemic brain Irreversible neuronal injury begins after 5 minutes of hypoxia. Most vulnerable: hippocampus disease\/stroke (CA1 region), neocortex, cerebellum (Purkinje cells), watershed areas (\u201cvulnerable hippos need pure water\u201d). Ischemic stroke A Stroke imaging: noncontrast CT to exclude hemorrhage (before tPA can be given). CT detects ischemic changes in 6\u201324 hr. Diffusion-weighted MRI can detect ischemia within 3\u201330 min. Transient ischemic attack TIME SINCE ISCHEMIC 12\u201324 HOURS 24\u201372 HOURS 3\u20135 DAYS 1\u20132 WEEKS > 2 WEEKS EVENT Eosinophilic Necrosis + Macrophages Reactive gliosis Glial scar Histologic cytoplasm neutrophils (microglia) (astrocytes) features + pyknotic + vascular nuclei (red proliferation neurons) Ischemia \u008e\u00a0infarction \u008e\u00a0liquefactive necrosis. 3 types: \u0083\t Thrombotic\u2014due to a clot forming directly at site of infarction (commonly the MCA A ), usually over a ruptured atherosclerotic plaque. \u0083\t Embolic\u2014due to an embolus from another part of the body. Can affect multiple vascular territories. Examples: atrial fibrillation, carotid artery stenosis, DVT with patent foramen ovale (paradoxical embolism), infective endocarditis. \u0083\t Hypoxic\u2014due to systemic hypoperfusion or hypoxemia. Common during cardiovascular surgeries, tends to affect watershed areas. Treatment: tPA (if within 3\u20134.5 hr of onset and no hemorrhage\/risk of hemorrhage) and\/or thrombectomy (if large artery occlusion). Reduce risk with medical therapy (eg, aspirin, clopidogrel); optimum control of blood pressure, blood sugars, lipids; smoking cessation; and treat conditions that \u008f\u00a0risk (eg, atrial fibrillation, carotid artery stenosis). Brief, reversible episode of focal neurologic dysfunction without acute infarction (\u229d MRI), with the majority resolving in < 15 minutes; ischemia (eg, embolus, small vessel stenosis). May present with amaurosis fugax (transient visual loss) due to retinal artery emboli from carotid artery disease. Cerebral edema Fluid accumulation in brain parenchyma \u008e\u00a0\u008f\u00a0ICP. Types: A \u0083\t Cytotoxic edema\u2014intracellular fluid accumulation due to osmotic shift (eg, Na+\/K+-ATPase dysfunction \u008e\u00a0\u008f\u00a0intracellular Na+). Caused by ischemia (early), hyperammonemia, SIADH. \u0083\t Vasogenic edema\u2014extracellular fluid accumulation due to disruption of BBB (\u008f\u00a0permeability). Caused by ischemia (late), trauma, hemorrhage, inflammation, tumors (arrows in A show surrounding vasogenic edema). uploaded by medbooksvn","528 SEC TION III Neurology and Special Senses\u2003 \uf07d\u2009neurology\u2014Pathology Effects of strokes ARTERY AREA OF LESION SYMPTOMS NOTES Anterior circulation Contralateral paralysis and Wernicke aphasia is associated sensory loss\u2014lower limb, urinary with right superior quadrant Anterior Motor and sensory cortices\u2014lower incontinence. visual field defect due to cerebral limb. temporal lobe involvement. artery Contralateral paralysis and sensory loss\u2014lower face and upper limb. Pure motor stroke (most Middle Motor and sensory cortices A \u2014upper common). Common cerebral limb and face. Aphasia if in dominant (usually location of lacunar infarcts artery left) hemisphere. Hemineglect B , due to microatheroma Temporal lobe (Wernicke area); if lesion affects nondominant and hyaline arteriosclerosis frontal lobe (Broca area). (usually right) hemisphere. (lipohyalinosis) 2\u00b0 to unmanaged hypertension. Lenticulo\u00ad Striatum, internal capsule. Contralateral paralysis. Absence striate of cortical signs (eg, neglect, Locked-in syndrome (locked artery aphasia, visual field loss). in the basement). Posterior circulation Lateral pontine syndrome. Facial nerve nuclei effects are Posterior Occipital lobe C . Contralateral hemianopia with cerebral macular sparing; alexia without specific to AICA lesions. artery agraphia (dominant hemisphere, extending to splenium of corpus Supplied by labyrinthine artery, Basilar artery Pons, medulla, lower midbrain. callosum); prosopagnosia a branch of AICA. (nondominant hemisphere). Corticospinal and corticobulbar tracts. If RAS spared, consciousness is preserved. Anterior Ocular cranial nerve nuclei, inferior paramedian pontine reticular Quadriplegia; loss of voluntary cerebellar formation. facial (except blinking), mouth, artery and tongue movements. Facial nerve nuclei. Loss of horizontal, but not vertical, Vestibular nuclei. eye movements. Spinothalamic tract, spinal Paralysis of face (LMN lesion vs trigeminal nucleus. UMN lesion in cortical stroke), \u0090\u00a0lacrimation, \u0090\u00a0salivation, \u0090\u00a0taste Sympathetic fibers. from anterior 2\u20443 of tongue. Middle and inferior cerebellar Vomiting, vertigo, nystagmus peduncles. \u0090\u00a0pain and temperature sensation Inner ear. from contralateral body, ipsilateral face. Ipsilateral Horner syndrome. Ipsilateral ataxia, dysmetria. Ipsilateral sensorineural deafness, vertigo.","Neurology and Special Senses\u2003 \uf07d\u2009neurology\u2014Pathology SEC TION III 529 Effects of strokes (continued) ARTERY AREA OF LESION SYMPTOMS NOTES Posterior Nucleus ambiguus (CN IX, X, XI). Dysphagia, hoarseness, \u0090 gag Lateral medullary (Wallenberg) inferior reflex, hiccups. syndrome. cerebellar Vestibular nuclei. artery Lateral spinothalamic tract, spinal Vomiting, vertigo, nystagmus Nucleus ambiguus effects are \u0090\u00a0pain and temperature sensation specific to PICA lesions D . trigeminal nucleus. from contralateral body, \u201cDon\u2019t pick a (PICA) lame Anterior Sympathetic fibers. ipsilateral face. (lateral medullary syndrome) spinal Inferior cerebellar peduncle. Ipsilateral Horner syndrome. horse (hoarseness) that can\u2019t artery Corticospinal tract. Ipsilateral ataxia, dysmetria. eat (dysphagia).\u201d Medial lemniscus. Contralateral paralysis\u2014upper and Medial Medullary syndrome\u2014 Caudal medulla\u2014hypoglossal nerve. lower limbs. caused by infarct of paramedian branches of ASA AB \u0090 contralateral proprioception. and\/or vertebral arteries. Ants Ipsilateral hypoglossal dysfunction love M&M\u2019s. (tongue deviates ipsilaterally). D C Neonatal Bleeding into ventricles (arrows in A show blood in intraventricular spaces on ultrasound). intraventricular Increased risk in premature and low-birth-weight infants. Originates in germinal matrix, a highly hemorrhage vascularized layer within the subventricular zone. Due to reduced glial fiber support and impaired autoregulation of BP in premature infants. Can present with altered level of consciousness, A bulging fontanelle, hypotension, seizures, coma. uploaded by medbooksvn"]