Mechanisms of Disease Exam 1
Terms
undefined, object
copy deck
-
Pathology of Osteoarthritis
1. gross level
2. microscopic level
3. biochemically -
1. - first, cartilage irregularities and splitting
- next, ulceration and loss of cartilage
- next, bone on bone contact then eburnation (polished bone)
2. - fibrillation of cartilage
3. - decreased glycosaminoglycan content of cartilage, including less chondroitin sulfate, less keratin sulfate and less hyaluronic acid
- increased MMP activity, which plays role in degradation of extracellular matrix of cartilage - Pathogenesis: OA is primarIly a disease of ________ of joints.
- hyaline cartilage
- Pathogenesis: the initiating event in OA is ______ which results in _______.
- mechanical stress, which results in change in chondrocyte metabolism - proteolytic enzyme production (MMPS)- disruption of cartilage matrix
- In OA, mechanical stress means...
- any compressional stress which too forcefully jams the 2 articulating surfaces of hyaline cartilage together.
- As OA progresses, crystals of _______ are shed into the joint fluid and are commonly found in severe OA.
- calcium phosphate
- Clinical features of OA
-
-pain and stiffness of joint, worse with use, better with rest, or vv.
-morning stiffness <30 min
-gelling
-osteophytes impinging on dorsal roots &/or spinal cord - radicular sx in limbs:pain, numb, weak - In OA, pain may be due to:
-
-inflammation of the periosteum (periostitis) at sites of bone remodeling
-subchondrial microfractures
-irritation of synovial nerve endings by osteophytes
-synovial inflammation from chemical junk - On physicacal exam, OA presents:
-
-warmth and soft tissue swelling of joint is minimal
-tenderness and bony enlargement of joint
-Crepitus from cartilage irregularities
-possible locking due to a loose piece of cartilage
-varus deformity of knee in 50% due to worse loss of cartilage - In OA, classic enlargement occurs at which joints?
- PIP joints (Bouchard's nodes) and DIP joints (Heberden's nodes)
- Radiologic features of OA:
-
-asymmetric joint space narrowing due to cartilage loss
-subchondral bone sclerosis
-subchondral bone cysts
-osteophytes - Labs of Osteoarthritis:
-
-Dx of OA is almost always by H&P and can be confirmed by XR
-WBC count in synovial fluid should be <200 cells per cubic mm - Treatment of OA:
-
-APAP, NSAIDS
-capsaicin cream (Zoxtrix)
-oral chondroitin sulfate or glucosamine
-intra-articular steroid injections
-intra-articular injection of hyaluronic acid derivatives
-arthroplasty (joint replacement) - The most feared possibility when a patient presents with a joint which is red, hot, swollen, painful joints is:
- Septic arthritis
- Which form of arthritis is monoarticular?
- Septic arthritis
- Septic arthritis is caused by...
- bacterial joint infection
- Hydrolytic enzymes from neutrophils destroy joint fast by irreversible cartilage reabsorption possibly resulting in sepsis and death.
- Septic arthritis
- Bacterial access to joint occurs by...
-
-hematogenous spread (endocarditis, IV drug use)
-contiguous osteomyelitis
-joint penetrating injury
-prosthetic joint
-joint injection - SA in children is often linked to _____ because of _____.
- osteomyelitis because of open epiphyses
- SA in teens & adults is often linked to _______.
- Neisseria gonorrheae infection
- Labs of SA:
-
-of all causes of SA, blood culture is + in 50%
-synovial fluid constituents indicate decreased glucose, increased protein & lactate, WBC count >10,000/ul - Treatment of SA:
-
-treat early with antibiotic
-Rocephin (ceftriaxone) or Nafcillin IV plus gentamicin IV - Name 3 diseases that present with red, hot, swollen joints.
-
1. Septic arthritis
2. Gouty arthritis
3. Reiter's disease - Clinical features of Lyme Disease
-
-rash in 50% of people
-if untreated, fatigue, fever, headache &/or arthralgias - If Lyme Disease goes untreated, a minority develop the following complications:
-
-arthritis (knee)
-neorologic: headaches, meningeal signs (nuchal rigidity), cranial nerve dysfunction (facial nerve-bilateral Bell's Palsy)
-Cardiac(AV block) - ELISA detects replacement of IgM with IgG and is confirmed by Western Blot.
- Lyme Disease
- Treatment of Lyme Disease
-
-Prevention: tick repellants
-Antibiotics: rash/arthritis - po Vibramycin (doxycycline) or Amox (amoxicillin); carditis/meningitis - IV Rocephin (ceftriaxone) - Arthritis which occurs after genitourinary, gastrointestinal and possibly respiratory infection.
- Reiter's Syndrome aka Reactive Arthritis
- Originally referred to as the clinical triad of arthritis, conjunctivitis, and nonconococcal urethritis.
- Reiter's Syndrome aka Reactive Arthritis
- Considered one of the seronegative spondyloarthropathies (SNSA)
- Reiter's Syndrome aka Reactive Arthritis
- SNSA
- seronegative spondyloarthropathies
- The SNSAs are:
-
-Reactive Arthritis
-Lyme Arthritis
-Psoriatic Arthritis
-Gouty Arthritis
-Osteoarthritis
-Septic Arthritis - Seronegative denotes absence of _________.
- rheumatoid factor
- Nongonococcal urethritis with C.trachomatus is frequently the trigger for _________.
- Reiter's Syndrome
- Clinical features of Reiter's Syndrome
-
-typically begins 2-4 weeks post gastroenteritis or venereal infx.
-nongonococcal urethritis
-conjunctivitis usually accompanies or follows
urethritis
-articular manifestations typically appear last
-extraarticular manifestations -
-dactylitis or sausage digits
-asymmetric oligoarthritis of lower extremities
-enthesopathy - articular manifestations of Reiter's Syndrome aka Reactive arthritis
- entheses
- attachment sites of tendons to ligaments
-
-Circinate balanitis
-Keratodermal blennorrhagica - Extra-articular manifestations of Reiter's Syndrome aka Reactive arthritis
- Circinate balanitis
- shallow ulcer of glans or shaft of penis
- Kertodermal blennorrhagica
- papulosquamous rash most often on palms or soles.
- Immunohistochemical studies of synovium reveal antigenic material from infecting organisms but no viable organisms.
- Reiter's Syndrome aka Reactive arthritis
-
-increased sed rate & C-reactive protein
-synovial fluid: turbid,WBC count >5000/ul,low viscosity - Labs for Reiter's Syndrome aka Reactive arthritis
- Consider Reactive arthritis when:
-
-asymmetric oligoarthritis esp. in young person
-extra-articular manifestations
-h/o prior infections supports Dx - Treatment of Reactive arthritis
-
-NSAIDs & exercise until arthritis remits
-rarely, systemic or intra-articular steroids
-DMARDs if no response to NSAIDs - DMARDs
- Disease Modifying Anti-Rheumatic Drugs
-
-increased epidermal cell turnover leading to acanthosis (thickening)
-pink-to-salmon plaques covered with silver scales
-nail changes (oil slick discoloration,pitting,thickening,oncholysis)
-Auspitz sign
-Koebner phenomenon - The skin condition Psoriasis
- Auspitz Sign
- multiple small bleeding points on skin when scrape gently or lift scales due to dilated tortuous capillaries under plaque
- Koebner Phenomenon
- psoriatic lesion develops at the site of minor skin trauma, surgical suture lines, etc.
- T/F: Psoriatic Arthritis is a seronegative spondyloarthropathy.
- True.
- T/F: Psoriatic Arthritis appears in psoriasis patients who have extensive skin leasions.
- True.
- ___________ arthritis may really be another form of Reactive Arthritis, ie. reactive to Staph and Strep antigens in ____________.
- Psoriatic Arthritis...psoriatic skin lesions.
-
-oligoarthritis most comm. spread through small joints (PIP,DIP, MCP), sausage digits
-Arthritis mutilans
-Extra-articular involvement (psoriatic skin lesions, nail changes, sausage digits, enthesopathy) - Psoriatic Arthritis
-
-pencil in cup deformity at phalanges
-acro-osteolysis=resorption of distal bone tuft of distal phalanx
-joint space loss - Radiologic features of Psoriatic arthritis
- Treatment of Psoriasis (Skin Disease)
-
-topical steroids (kenalog cream)
-topical coal tar preps (Psorigel)
-Vit. D derivatives (Dovonex)
-Vit. A derivatives(Soriatane)
-PUVA=pulsed UVA light
-Rheumatrex (methotrexate)
-Enbrel (etanercept) - Treatment of Psoriatic Arthritis
-
-NSAIDs
-intra-articular steroid injections
-Enbrel
-DMARDs (Rheumatrex, Azulfidine) - A metabolic disease; hyperuricemia in the blood, which has musculoskeletal consequences
- Gouty Arthritis
- Uric acid comes from the breakdown of _______, _______ & ________.
- purines, adenosine & guanosine
- Patients with Gout
-
-mostly men, peak in 40s
-hyperuricemia
-at higher plasma concentrations of urate, monosodium urate crystals precipitate out of solution into cooler peripheral joints (ankles, toes) and tissues (ears & fingers) - Clinical Presentation of Gout
-
-abrupt: usually one joint(MTP,ankle,knee). Pt often well at bedtime, awakes w/podagra. exquisitely painful.
-attack resolves in days to weeks despite crystals still in joint - Factors which precipitate acute attack of Gout
-
-start of uric acid therapy (allpurinol)
-start of diuretic therapy
-surgery/trauma, severe illness, stroke, acute myocardial infarction
-alcohol binges -
Clinical Presentation of Gout
1. Intercritical Phase
2. Subsequent Attacks
3. If untreated -
1. all quiet, but most have recurrence w/in 2 years of 1st attack
2. often worse: high fever & chills suggesting septic joint;more likely to involve upper extremity joints &/or multiple joints
3. shorter intercritical phases & progressive joint destruction;urate crystals in soft tissue - gouty tophi
-
urate crystals in soft tissue
(ear pinnae,olecranon bursa,fingers & toes, achilles tendon) - Diagnosis of Gout
-
-Pt presents with abrupt onset mono or oligoarthritis of lower extremity
-Hyperuricemia >6-7mg/dl
-aspiration of fluid shows needle-shaped, negatively bifringent, monosodium urate crystals - Treatment for Acute Attack of Gouty Arthritis
-
-NSAIDS:Indocin(indomethacin),Advil(Ibuprofen),Anaprox(naproxen)
-Cochicine-90% get relief and this supports dx of gout
-Steroids-if can't use above - _______ is contraindicated for treatment of Gout because in small doses it may worsen hyperuricemia.
- Aspirin
- Prophylaxis and Uric Acid Lowering TX of Gout
-
-lose weight and lose the boose
-avoid dehydration and diuretics
-get serum urate below 5mg/dl - In a condition called ______, calcium pyrophosphate crystals are at fault. These crystals are ____________ bifringent.
- Pseudogout, positively
- Diagnosis of Pseudogout
-
-patient presents with abrupt onset mono or oligoarthitis
-serum urate level NOT elevated
-aspiration of joint fluid shows: calcium pyrophosphate crystals and NO bacteria - Treatment of Pseudogout
-
-urate lowering drugs are irrelevant
-NSAIDS
-Cochicine(may or may not be beneficial for acute attack but given prophylactically it decreases the # & duration of attacks
-intra-articular steroids will terminate attacks in resistant cases - A chronic inflammatory systemic disease dominated by joint destruction
- Rheumatoid Arthritis
- ________ arthritis is considered a symmetric polyarthritis
- Rheumatoid
- symmetric polyarthritis
- arthritis that affects homologous joints on both sides of the body
- Joints commonly affected in RA are:
-
-MCP and PIP joints
-carpal bones and wrist
-Knees and MTP joints -
-synovial microvasculature
-hyperplasia of Type A & B synoviocytes
-early T cell emigration & infiltration into synovial tissue
-proliferation of blood vessels and of synovial fibroblasts (hypertrophic synovium)
-hypertrophied - Earliest changes of Rheumatoid arthritis
- Pathogenesis: Joint damage in ______ arthritis is of immune origin, ie. an autoimmune disease, in genetically disposed individuals.
- Rheumatoid
- The autoimmune response of this disease is due partly to Type 3 Hypersensitivity , ie. immune complex-mediated tissue injury. 80% of pts have RFs, which result in the attraction of WBC causing inflammation.
- Rheumatoid arthritis.
- RFs
- Rheumatoid factors - autoantibodies to the Fc portion of IgG in the serum and synovial fluid.
- Essential for Diagnosis of RA
-
documentation of inflammatory synovitis
-by synovial fluid leukocytosis (WBC >2000)
-typical erosions on XR -
-RF found in 80% of patients
-increased ESR and C-reactive protein (CRP)
-anemia of chronic disease - Labs of RA
- Synovial hypertrophy and pannus formation may cause peripheral nerve entrapment in selected joints.
- Rheumatoid Arthritis
- morning stiffness greater than 2 hours
- Rheumatoid Arthritis
- morning stiffness less than 30 minutes
- Osteoarthritis
-
-frozen shoulder (adhesive capsulitis)
-ulnar nerve entrapment-paresthesias of 4th/5th digi
-Baker's Cyst(post.herniation of joint capsule)
-Tarsal Tunnel Syndrome-entrapment of post.tibial nerve-parethesias of sole
-MTP Subluxations< - Rheumatoid Arthritis
-
Deformed hands:
-MCP and PIP joints involved
-nodules in finger tendons (locking)
-tendon rupture-Swan Neck & Boutonniere Deformity
-Opera Glass hands-ulnar deviation at MCP joints, radial deviation at wrists - Rheumatoid Arthritis
- Extraarticular Manifestations of Rheumatoid Arthritis
-
-Skin: nodules in skin,bursae,tendons &/or over pressure points
-Ocular: Keratoconjunctivitis sicca
-Respiratory: interstitial fibrosis, pluerisy/pleural effusion
-Heart: pericardial effusion, restrictive pericarditis w/sns of RHF
-GI: gastritis & peptic ulcer dz from NSAID tx
-Blood: anemia of chronic dz -
-NSAIDS (Advil,Arthrotec, Daypro,Alleve)
-Corticosteroids(glucocorticoids)
-DMARDS - Treatment for RA
- The prototype of autoimmune diseases, characterized by production of antibodies to components of cells in the nucleus.
- Systemic Lupus Erythematosus (SLE)
-
Dominated by:
-severe fatigue
-arthralgias/arthritis
-some permutation of its many systemic effects, many of which are vasculitic - SLE
- Used to be called connective tissue diseases or collagen vascular disease because of the prominence of effects in connective tissue and in blood vessels themselves
- SLE and other autoimmune diseases
- central disturbance is rampant production of auto-antibodies to a variety of self antigens in/on the cell surface, cytoplasm or nucleus
- SLE
- In SLE, auto-antibody production is due to immune cell abnormalities of the _____
- B cells, T cells and monocytes
- In SLE, abnormalities to immune cells cause:
-
-B cell hyperactivity leading to hyperglobulinemia
-Increased # of Ab producing cells
-Heightened responses to both foreign and self Ags - Immuno complex (IC) deposition results in inflammation and vasculitis of various organs and tissues
- SLE
- Anti-nuclear antibodies bind to self-antigenic components of _____, _____, _____, _____
- DNA, RNA, nuclear proteins, protein-nucleic acid complexes
-
Labs:
-generic ANAs
-anti-dsDNA Abs
-anti-Smith Abs
-C reactive protein is low even when sed rate is high - SLE
- _____ Abs in a lupus patient may fluctuate over time but _____ Abs remain more constant.
- anti-dsDNA, anti-Smith
-
Skin manifestations:
-malar, butterfly rash
-general erythema, often photosensitive
-discoid lesions=red papules or plaques with thick scale and hypopigmented center
-alopecia
-mucus membrane lesions
-Raynaud's Phenomenon - Skin Manifestations of SLE
-
Musculoskeletal manifestations:
-arthralgias & arthritis
-arthritis similar to RA but not erosive
-myalgias
-fibromyalgia - Musculoskeletal Manifestations of SLE
-
Manifestations of Renal Dysfunction:
-glomerulonephritis, nephrotic syndrome, renal failure - Renal Manifestations of SLE
-
Neuropsychiatric Manifestations:
-CNS problems, cranial and peripheral neuropathies, psychiatric problems: intractable headaches, seizures,chorea,CVA,cranial neuropathies,peripheral neuropathies,organic brain syndrome - Neuropsychiatric Manifestations of SLE
-
Serositis:
-Pleurisy
-Pericarditis - serositis of SLE
-
GI Manifestations:
-abdominal pain, nausea/vomiting, anorexia due to diffuse peritonitis, pancreatitis, IBD, mesenteric vasculitis - GI Manifestations of SLE
-
Pulmonary Manifestations:
-pneumonitis
-pulmonary hemmorhage due to pulmonary vasculitis
-pulmonary hypertension - Pulmonary Manifestations of SLE
-
Cardiac Manifestations:
-pericarditis
-myocarditis -- CHF
-endocarditis
-coronary vasculitis
-atherosclerosis leading to AMI - Cardiac Manifestations of SLE
-
Vascular Manifestions
-acute necrotizing vasculitis - Vascular Manifestions of SLE
-
Reticuloendothelial System
-splenomegaly
-lymphadenopathy, at single or multiple sites, nodes soft & tender - Reticuloendothelial Manifestions of SLE
-
Hematologic Manifestations
-increased sed rate
-cytopenias - Hematologic Manifestations of SLE
- Treatment for SLE
-
-avoid sun
-NSAIDs & steroids
-DMARDs - Clinical course of SLE
-
-usually relapsing-remitting
-some have downhill course to death in months
-10 year survival = 70% - Dominated by fibrotic and degenerative skin changes.
- Scleroderma
- Includes the changes of scleroderma plus systemic fibrosis and systemic vascular injury.
- Systemic Sclerosis
-
Scleroderma is aka ____.
Systemic Sclerosis is aka ____. -
Limited Scleroderma
Diffuse Scleroderma - CREST comprises most of the manifestations of ________ and it stands for_______.
-
-Limited Scleroderma
-Calcinosis, Raynaud's Phenomenon, Esophageal Dysmotility, Sclerodactyly, Telangectasias - Calcinonis
- subcutaneous tissues develop calcifications that are either palpable, visible as radio-opacities on Xray or both. Fingertips most often.
- Raynaud's Phenomenon
- Painful, triphasic color change in acral areas, ie. fingers, toes, nose, ears. In response to cold exposure or stress, the acral arterioles constrict (ischemia-white). Next the area becomes cyanotic (blue) probably because the arterioles redilate slightly and perfusion is so minimal that blood releases oxygen. Next, arterioles dilate greatly (reactive hyperemia -very red)
- Esophageal Dysmotility
-
atrophy and fibrosis of the esophagus causes:
-dysphagia
-LESD which causes GERD, Barrett's esophagus (metaplasia of epithelial cells of lower esophagus leading to precancerous lesion) from chronic GERD - Sclerodactyly
-
-first manifestation to occur in crest is diffuse edema of fingers and hands later replaced by skin thickening and tightness
-eventually, claw-like hand w/tapered fingers w/tight, shiny skin
-skin change later affects face, pulling into a tight mask with bared teeth - Telangectasias
-
-most commonly result from alcohol abuse
-permanently dilated blood vessels of the nose and cheeks
-in Scleroderma, it is more widespread and occurs w/o alcohol - anti-centromere antibodies
- Limited Scleroderma
- SCL-70 antibodies
- Diffuse Scleroderma aka Systemic Scleroderma
- Fibrotic and vascular changes that originally affected only the hands, esophagus and face intensify in those areas and cause problems in other systems
- Diffuse Scleroderma aka Systemic Scleroderma
- Skin Manifestations of Systemic (Diffuse) Scleroderma
-
-skin changes spread to arms, legs, trunk
-scattered hyperpigmentation of skin creates S&P appearance
-involved skin loses sweat glands and hair follicles
-hand skin becomes so tight that finger motility is impaired
-mouth becomes so tight that eating & oral hygiene become difficult
-ischemia of the fingers causes skin ulcers, necrosis and then loss at the tips - GI Manifestations of Systemic (Diffuse) Scleroderma
-
-anywhere from mouth to rectum
-fibrosis of small bowel leading to hypomotility, cramping, bloating
-colon develops wide-mouth saccular diverticuli - Cardiac Manifestations of Systemic (Diffuse) Scleroderma
-
-pericardial effusion may impair ventricular filling
-coronary vasospasm leads to left ventricular dysfunction
-systemic hypertension leading to left ventricular hypertrophy and failure
-pulmonary fibrosis leading to pulmonary hypertension and right ventricular hypertrophy and failure - Pulmonary Manifestations of Systemic (Diffuse) Scleroderma
-
-pulmonary fibrosis (restrictive lung disease & right ventricular failure)
-fibrosis causes decreased alveolar oxygen uptake - Kidney Manifestations of Systemic (Diffuse) Scleroderma
- -marked sclerosis of arteries -->decreased GFR--> progressive azotemia and increased renin secretion--> malignant hypertension
- Musculoskeletal Manifestations of Systemic (Diffuse) Scleroderma
-
-joint pain and stiffness due to skin tightness and tendon involvement
-friction rubs/crepitus of large joint (knee) due to fibrosis of synovium
-flexion contractures of fingers, wrist and elbow from fibrosis of synovium and periarticular structures - Clinical Course of Systemic (Diffuse) Scleroderma
-
-unpredictable, generally slowly progressive
-CREST syndrome may remain nonprogressive for long periods
-prognosis is poor if cardiac, pulmonary or renal involvement - Treatment for Systemic (Diffuse) Scleroderma
- -no cure and nothing alters course of disease for long. Therefore, treatment is symptomatic.(Treat individual manifestations)Also, steroids provide no benefit in this time of inflammation.
-
Treatment for:
-Raynaud's
-GERD
-Hypertension -
-calcium channel blockers, angiotensin II receptor blockers
-antacids, anti-histamines (H2 blockers), proton pump inhibitors
-ACE-inhibitors - Immune-mediated inflammatory disorder of exocrine glands dominated by salivary and lacrimal gland dysfunction (dryness).
- Sjogren's Syndrome
- Primary Sjogren's Syndrome
- when mucous membrane dryness and its related effects occur in isolation, it is called ______.
- Secondary Sjogren's Syndrome
- When other autoimmune diseases, notable RA, SLE and Systemic Sclerosis, may themselves cause similar exocrine gland degeneration and dysfuntion, it is known as ________.
- Clinical Features of Sjogren's Syndrome
-
Dysfunction of:
1. Lacrimal Gland - dry, irritated eyes with foreign body sensation; corneal abrasions
2. Salivary Gland - dry mouth, oral sores and dental caries;lingual and labial fissures, dysphagia and GERD, parotid and/or submandibular gland swelling and tenderness
3. other mucous membrane - dry vaginal membranes (dyspareunia);recurrent or persistent sinusitis, dry tracheobronchial membrances leading to URI (pneumonia);pancreatic dysfn leading to nutrient malabsorption -
anti-SS-A Ab aka anti-Ro Ab
anti-SS-B Ab aka anti-La Ab - Sjogren's Syndrome
- Pathology: Emigration of CD4 T-lymphocytes come in direct contact with ductal epithelial cells, causing cell mediated gland destruction
- Sjogren's Syndrome
- Diagnosis of Sjogren's Syndrome
-
-suspect SS if patient presents with chronically dry eys and mouth, esp. with mild joint pain
-ROSE BENGAL TEST=staining of cornea for abrasion
-Whole Saliva Sialometry=patient sucks on sugarless candy for 3 min. and spits watching for decreased secretions.
-SCHIRMER's Test=measure of the quant. of tears secreted in 5 min. in response to irritation by a strip of Schirmer's filter paper under each lower eyelid.
-young moisten 15mm, 1/3 of elderly moisten 10mm, SS will moisten <5mm -
Labs:
-salivary gland biopsy
-70% have elevated ESR - Labs for Sjogren's Syndrome
- Treatment for Sjogren's Syndrome
-
-avoid meds w/anticholinergic effects since much exocrine gland function is cholinergic
-treat Keratoconjunctivitis sicca, Xerostomia, dyspareunia, nephritis, pneumonitis, neueropathy, etc. - Treatment for Keratoconjunctivitis sicca
-
-hypotears (artificial tears)
-HydroEye caps = blend of omega-6 fatty acids and mucin - Treatment for Xerostomia
-
-stimulate saliva (sugarless gum, chewing paraffin or sucking on fruit pit, oral pilocarpine)
-Evoxac(cevimeline)=cholinergic agonist-salivation
-Fluoride treatment against caries in absence of saliva - Inflammatory disease of muscle.
- Polymyositis
- Inflammatory disease of muscle with a variety of dermatologic manifestations.
- Dermatomyositis
- four main categories of clinical features of PM & DM
-
1. Proximal muscle weakness
2. Elevated serum levels of skeletal muscle enzymes
3. Electromyographic evidence of myopathy
4. Biopsy evidence of muscle inflammation
5. Skin rash - permits the Dx of Dermatomyositis - slow onset over 3 to 6 months without an identifiable precipitating event
- Polymyositis/Dermatomyositis
- 3 main components of Acute Inflammation
-
1. Local Hyperemia:from local arteriolar vasodilation-inc'd flow volume but dec'd flow velocity-neutros & RBC to site
2. Vascular Permeability:leakage of water,plasma proteins and neutrophils into tissue-swelling & pain
3.Leukocyte Emigration:accumulation, leakage & subsequent movement of neutrophils into the tissue by dec'd laminar flow - Histamine, Bradykinin, Leukotrienes, IL-1, TNF
- chemical mediators of inflammation aggravate leakiness
- after moving into the tissues, the neutros move toward the site of injury along gradients of _____.
- chemotactic factors (chemical junk)
- Vasoactive amines
- chiefly histamine, found in mast cells adjacent to capillaries and venules, and in circulating basophils and platelets.
- Histamine causes _____, _____ and therefore ______.
- arteriolar dilation, venular leakage, edema.
- Eicosanoids
- the prostaglandins and leukotrienes
- Prostaglandins and Leukotrienes lead to:
- fever, pain, edema, vasodilation, bronchospasm
- Which pathway do NSAIDs block?
- cyclooxygenase pathway
- Which pathway do steroids block?
- phospholipid-induced production of arachidonic acid
-
a) Leukotriene receptor antagonists
b)5-lipoxygenase inhibitor -
a) Accolate (zafirlukast)
Singulair (montelukast)
b) Zyflo (zileuton) - off market - Acute phase reactions associated with injury or infection and induced by IL-1,IL-6, and TNF
- -fever,lethargy,dec'd appetite,inc'd neutrophil count,ACTH release leading to corticosteroid release,hepatic synthesis of various proteins (acute phase reactants)
- acute phase reactants
-
-fibrinogen
-C-reactive protein
-complement - In inflammation, the increased levels of _____ in the blood cause the sed rate to increase significantly.
- fibrinogen
- What role does Nitric Oxide play in the inflammation process?
- vasodilation
- Lysosomal enzymes
-
-elastase
-alpha1-antitrypisin: counteracts elastase - Outcomes of Acute Inflammation (4)
-
1. Complete resolution
2. Scarring
3. Abscess formation: occurs when injury is due to pyogenic bacteria
4. Progression to chronic inflammation - Chronic inflammation is seen in what 4 settings?
-
1. persistent infection
2. prolonged exposure to toxic agents
3. autoimmune disease
4. sarcoidosis - Chronic inflammatory cells
- macrophages, lymphocytes, plasma cells
- Granulomatous Inflammation
- distinctive form of chronic inflammation, characterized by aggregation of activated macros that develop a squamous "epitheloid" appearance. It may also become surrounded with fibroblasts and connective tissue
- The role of the lympatics:
- to remove inflammatory fluid and debris from the interstitial space
- To prevent the normal net leakage of plasma proteins into the brain, and to prevent exposure to drugs, toxins or hormones that may enter the body, brain capillaries have:
- blood brain barrier - tighter endothelial cell junctions
- _______ allows penetration of the BBB by antibiotics, which is typically very selective.
- Vascular permeability caused by inflammation
- Morphologic Patters in Acute and Chronic Inflammation (4)
-
1. Serous Inflammation
2. Fibrinous Inflammation
3. Suppurative Inflammation
4. Ulceration - necrosis and erosion