UNIVERSITY OF ILLINOIS COLLEGE OF MEDICINE AT URBANA-CHAMPAIGN PATHOLOGY - VOLUME III 2015-2016 PATHOLOGY TEACHING FACULTY LIST Jerome Anderson, MD Farah Gaudier, MD Richard Tapping, PhD Department of Pathology Dept. of Pathology Associate Professor McDonough District Hosp. Carle Physician Group Dept. of Microbiology McComb, IL 61455 [email protected] [email protected] Phone: (309) 837-2368 [email protected] Brett Bartlett, MD Nasser Gayed, MD Teaching Assistant Dept. of Pathology 190 Medical Sciences Bldg Contact J. Newman 506 South Mathews Avenue SBL Health Centre Urbana, IL 61801 Mattoon IL 61938 [email protected] Frank Bellafiore, MD Nicole Howell, MD Pathology Office Dept. of Pathology Dept. of Pathology Ms. Jackie Newman Carle Physician Group ( 217) 244 – 2265 602 West University Avenue Carle Physician group [email protected] Urbana, IL 61801 [email protected] [email protected] Allan Campbell, MD Zheng George Liu, MD Dept. of Pathology Dept. of Pathology UICOM Peoria IL Carle Physician group 602 West University Avenue Urbana, IL 61801 [email protected] Gregory Freund, MD Steve Nandkumar, MD Head, Dept. of Pathology Pathology Course Director 190 Medical Sciences Building 249 Medical Sciences Building 506 South Mathews Avenue 506 South Mathews Avenue Urbana, IL 61801 Urbana, IL 61801 [email protected] [email protected] GOLF BALLS, PEBBLES, SAND, AND BEER Remember the Mayonnaise Jar A professor stood before his philosophy class with some items in front of him. When the class began, wordlessly, he picked up a very large and empty mayonnaise jar and proceeded to fill it with golf balls. He then asked the students if the jar was full. They agreed that it was. The professor then picked up a box of pebbles and poured them into the jar. He shook the jar lightly and the pebbles rolled into the open areas between the golf balls. He asked the students again if the jar was full. They agreed that it was. Next, the professor picked up a box of sand and poured it into the jar. Of course, the sand filled up everything else. He asked once more if the jar was full. The students responded with a unanimous “Yes!” The professor then produced two cans of beer from under the table and poured the entire contents into the jar, effectively filling the empty space between the sand. The students laughed. “Now,” said the professor as the laughter subsided, “I want you to recognize that this jar represents your life. The golf balls are the important things: your family, your children, your health, your friends, and your favorite passions – things that if everything else was lost and only they remained, your life would still be full. “The pebbles are the other things that matter: your job, your house, your car. The sand is everything else – the small stuff. If you put the sand into the jar first,” he continued, “there is no room for the pebbles or the golf balls. The same goes for life. If you spend all your time and energy on the small stuff, you will never have room for the things that are important to you. Pay attention to the things that are critical to your happiness. Play with your children. Take time to get medical checkups. Take your partner out to dinner. Play another 18. There will always be time to clean the house and fix the disposal. Take care of the golf balls first, the things that really matter. Set your priorities. The rest is just sand.” One of the students raised her hand and inquired what the beer represented. The professor smiled and said, “I’m glad you asked. It just goes to show you that no matter how full your life may seem, there’s always room for a couple of beers.” CLP, October, 2006 Dear M2s, The 2.5 hour NBME subject exam on Mon. March 28 , 2016 will cover the entire Pathology course/lectures/labs. There will be 125 multiple choice questions including 15-17 images. JOINT DISEASES This session is covered in Dec. 2015 Steve Nandkumar, M.D. Pathology M-2 –Joint Diseases JOINT DISEASES NORMAL JOINT Joints (articulations) are structures that unite two or more bones. They provide both movement and mechanical support. Joints are of two types Synovial Non-synovial (Diarthroses or cavitated) (Synarthroses or solid) SYNOVIUM A smooth membrane lining the joint capsule and attached to the bone (osseous insertion). It is one to four cell layers in thickness. The synovial cells (synoviocytes) produce various proteins, Ig, lysozymes, and hyaluronic acid and also have phagocytic functions. SYNOVIAL FLUID It is a filtrate of plasma + hyaluronic acid. It serves as a lubricant and provides nutrition to the articular cartilage. ARTICULAR CARTILAGE A hyaline cartilage, 2–4 mms thick, serves as a shock absorber and provides wear resistant surface Hyaline cartilage = Type 2 collagen, water, proteoglycans ( chondroitin sulfate, Keratan sulfate), chondrocytes Type 2 collagen → tensile strength, transmits weight (load). Force per cubic cm of articular cartilage is unit load. Water and proteoglycans → turgor and elasticity NOTE: The articular cartilage has no vascular, lymphatic, or nerve supply 1 Pathology M-2 –Joint Diseases CHONDROCYTES produce Type 2 collagen + Proteoglycans matrix synthesis + Enzyme inhibitors (TIMP) In balance degrading enzymes matrix degradation (MMP) CYTOKINES such as IL-1 and TNF produced by chondrocytes, synoviocytes, fibroblasts and inflammatory cells cause matrix degradation. NOTE: MMP – Matrix metalloproteinases TIMP – Tissue inhibitor of metalloproteinases OSTEOARTHRITIS Also known as Degenerative Joint Disease (DJD). DEFINITION – An intrinsic disease of the articular cartilage characterized by biochemical and metabolic changes causing erosion and degeneration. – This is NOT a primary inflammation of the joint. Any inflammation that occurs is secondary. OSTEOARTHRITIS PRIMARY OR IDIOPATHIC SECONDARY (5% OF CASES) AGE RELATED 1. Macro or microtrauma to joint – May affect single or 2. Congenital deformity multiple joints 3. Diabetes mellitus – Stress-related wear and 4. Ochronosis tear of articular cartilage 5. Hemochromatosis 6. Marked obesity NOTE: Ochronosis is alkaptonuria – An inborn error of metabolism associated with deficiency of homogentisic acid oxidase leading to deposition of homogentisic acid in tissues → OA 2 Pathology M-2 –Joint Diseases RISK FACTORS Age Increasing incidence of OA with increasing age, 80 – 90%% incidence > 65 years. Gender Male – Hips Female – Fingers and knees Race Whites > Non-whites Occupation RSI repetitive stress injury, e.g., ballet dancers → ankles, basketball players → knees, shoulders, elbows, baseball players → shoulders, elbows Genetics Susceptible genes on chromosomes 2 and 11; genes for PG ( prostaglandins) and WNT ( Wingless Integration 1) pathways Hormones Increased risk with elevated estrogens and increased bone density PATHOGENESIS Normal articular cartilage performs two functions: – Ensure friction-free movement with the help of synovial fluid – Act as a shock absorber in weight bearing joints (load is spread across the joint surface so that bones can handle it) For the above functions the cartilage must be: – ELASTIC – RESILIENT WITH HIGH TENSILE STRENGTH Cartilage is formed by Type II collagen, proteoglycans, and water. CHONDROCYTES produce Type II collagen and proteoglycans (the cartilaginous matrix) but are also responsible for matrix degradation by secreting degrading enzymes (along with enzyme inhibitors). Normally matrix synthesis = matrix degradation. If chondrocytes do not function well, the integrity of the matrix is affected and disease (DJD) develops (more degeneration than regeneration). In DJD, for reasons that are not clear, chondrocytes produce IL-1, TNF-α, and NO etc. These stimulate production of catabolic metalloproteinases; inhibit the synthesis of Type II collagen and proteoglycans. THERE IS INCREASED WATER ACCUMULATION AND DECREASED PROTEOGLYCANS IN THE CARTILAGE ALONG WITH APOPTOSIS OF CHONDROCYTES. IL-6 and prostaglandins also ↑ matrix degradation. Thus, the net result is CARTILAGE DESTRUCTION. Cytokines are pro inflammatory and so inflammatory cells are seen in DJD. MORPHOLOGY Chondrocyte damage causes initial focal proliferation but they are lost with time – Superficial areas of the articular cartilage are eroded/degraded and SHOW SPLITTING (FIBRILLATION) AND FRAYING CHONDROMALACIA – FISSURES formed extend through the thickness of the cartilage and into the subchondral bone – Subjacent bone is thickened and ivory-like in consistency (EBURNATION) due to pressure. – Fragments of cartilage/bone dislodge and float freely in the joint cavity (joint mice!) – Subchondral bone cysts develop due to synovial fluid accumulation (driven through cracks in the cartilage/bone). – OSTEOPHYTES (bony outgrowths or spurs) capped by hyaline and fibrous cartilage are seen at the margins. – Mild chronic synovitis (non-specific) noted; synovial pannus forms 3 Pathology M-2 –Joint Diseases CLINICAL FEATURES Insidious disease; occurs in 50’s age group. – Deep achy joint pain and stiffness in the morning; limitation of movement – Crepitus (crackling sound due to exposed bones rubbing against each other) – Joint swelling and effusion – Heberden nodes (osteophytes in the DIP joint of fingers) in women (not in men) Bouchard’s nodes (osteophytes in PIP joint of fingers) – Osteophytes may compress nerve roots (radicular pain, muscle spasm, atrophy, neuro deficits etc.) – Commonly knee, hip, hands, feet, cervical and lumbar areas involved. Course – Slow progressive course with long–term disability. Surgery (joint replacement)