PATHOPHYSIOLOGY UNIT-1 .Basic Principles of Cell Injury And
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Calcinosis Cutis
Dermatology Online Journal UC Davis Calcinosis cutis: A rare feature of adult dermatomyositis Inês Machado Moreira Lobo, Susana Machado, Marta Teixeira, Manuela Selores Dermatology Online Journal 14 (1): 10 Department of Dermatology, Hospital Geral de Santo António, Porto, Portugal. [email protected] Abstract Dermatomyositis is an idiopathic inflammatory myopathy with characteristic cutaneous manifestations. We describe a case of a 55- year-old woman with dermatomyositis who presented with dystrophic calcinosis resistant to medical treatment. Dermatomyositis is an idiopathic inflammatory myopathy with characteristic cutaneous manifestations, including heliotrope rash, Gottron papules, periungual telangiectasias, photodistributed erythema, poikiloderma, and alopecia. Although heliotrope rash and Gottron papules are specific cutaneous features, calcinosis of the skin or muscles is unusual in adults with dermatomyositis. However, it may occur in up to 40 percent of children or adolescents [1]. Calcinosis cutis is the deposition of insoluble calcium salts in the skin. Calcinosis cutis may be divided into four categories according to the pathogenesis as follows: dystrophic, metastatic, idiopathic, and iatrogenic. In connective tissue diseases, calcinosis is mostly of the dystrophic type and it seems to be a localized process rather than an imbalance of calcium homeostasis. Calcium deposits may be intracutaneous, subcutaneous, fascial, or intramuscular. Clinical synopsis A 55-year-old woman was referred for evaluation because of multiple, firm nodules of the lateral hips since 1994. At that time, dermatomyositis was diagnosed based on cutaneous, muscular and pulmonary involvement. The nodules, gradually enlarging since 1999, have begun to cause incapacitation pain and many exude a yellowish material suggestive of calcium. She denied an inciting traumatic event. -
Soft Tissue Calcification and Ossification
Soft Tissue Calcification and Ossification Soft-tissue Calcification Metastatic Calcification =deposit of calcium salts in previously normal tissue (1) as a result of elevation of Ca x P product above 60-70 (2) with normal Ca x P product after renal transplant Location:lung (alveolar septa, bronchial wall, vessel wall), kidney, gastric mucosa, heart, peripheral vessels Cause: (a)Skeletal deossification 1.1° HPT 2.Ectopic HPT production (lung / kidney tumor) 3.Renal osteodystrophy + 2° HPT 4.Hypoparathyroidism (b)Massive bone destruction 1.Widespread bone metastases 2.Plasma cell myeloma 3.Leukemia Dystrophic Calcification (c)Increased intestinal absorption =in presence of normal serum Ca + P levels secondary to local electrolyte / enzyme alterations in areas of tissue injury 1.Hypervitaminosis D Cause: 2.Milk-alkali syndrome (a)Metabolic disorder without hypercalcemia 3.Excess ingestion / IV administration of calcium salts 1.Renal osteodystrophy with 2° HPT 4.Prolonged immobilization 2.Hypoparathyroidism 5.Sarcoidosis 3.Pseudohypoparathyroidism (d)Idiopathic hypercalcemia 4.Pseudopseudohypoparathyroidism 5.Gout 6.Pseudogout = chondrocalcinosis 7.Ochronosis = alkaptonuria 8.Diabetes mellitus (b) Connective tissue disorder 1.Scleroderma 2.Dermatomyositis 3.Systemic lupus erythematosus (c)Trauma 1.Neuropathic calcifications 2.Frostbite 3.Myositis ossificans progressiva 4.Calcific tendinitis / bursitis (d)Infestation 1.Cysticercosis Generalized Calcinosis 2.Dracunculosis (guinea worm) (a)Collagen vascular disorders 3.Loiasis 1.Scleroderma -
Università Degli Studi Di Milano
UNIVERSITÀ DEGLI STUDI DI MILANO SCUOLA DI DOTTORATO IN MEDICINA MOLECOLARE CICLO XXVIII Anno Accademico 2014/2015 TESI DI DOTTORATO DI RICERCA MED09 STUDIES OF HEME-REGULATED eIF2α KINASE STRESS SIGNALING ON MATURATION OF MACROPHAGES AND ERYTHROBLASTIC ISLAND FORMATION IN IRON RESTRICTIVE ERYTHROPOIESIS Dottorando : Elena PALTRINIERI Matricola N° R10203 TUTORE : Chiar.ma Prof.ssa Maria Domenica CAPPELLINI CO-TUTORE: Prof.ssa Jane-Jane CHEN DIRETTORE DEL DOTTORATO: Chiar.mo Prof. Mario CLERICI ABSTRACT Iron is the most important metal for the human body. Different states of iron deficiency have long existed and remain very common in today’s population. The vast majority of cases of iron deficiency are acquired as a result from blood loss. Any condition in which dietary iron intake does not meet the body’s demands will result in iron deficiency. Iron and heme are both fundamental in hemoglobin synthesis and erythroid cell differentiation. In addition to act as a prosthetic group for hemoglobin, heme regulates the transcription of globin genes and controls the translational activity in erythroid precursors through modulation of the kinase activity of the eIF2α kinase HRI which is regulated by heme. HRI, the heme-regulated inhibitor of translation, was first discovered in reticulocytes under the conditions of iron and heme deficiencies. During heme deficiency conditions, in the erythroid precursors protein synthesis is inhibited by phosphorylation of the α-subunit of the eukaryotic initiation factor 2 (eIF2α) as the result of the activation of HRI. The role of HRI is to control that the amount of globin chains synthesized are not in excess of what can be utilized for hemoglobin tetramers depending of heme available. -
General Pathology
Jordan University of Science and Technology Faculty of Medicine 2018-2019 COURSE TITLE : GENERAL PATHOLOGY. COURSE CODE : MED 231. CREDIT HOURS : 3 CREDIT HOURS SEQUENCE : YEAR 2, FIRST SEMESTER COURSE COORDINATOR: Dr. Alia AlMuhtaseb; Dr. Mohammad Orjani CONTACT: [email protected]; [email protected] Course Description: This course deals with the investigation of those pathological mechanisms common to all tissue-cell pathology. Attention is paid to the processes of cellular adaptation, inflammation, repair, immunology, cellular accumulation, and neoplasia. Lecture will attempt first to familiarize the student with our basic layers of defense. Next those vocabulary terms and concepts relevant to the disease process will be introduced. The terminology employed is both medical and chiropractic. Processes and concepts will be developed with the aid of Data show. An interactive format is employed in which the instructor poses questions to enable the student to self-test their knowledge prior to exams and develop skills in communicating these basic pathological concepts to others. During the course and whenever relevant the students are exposed to clinical problems to emphasize the explanations of symptoms, signs, investigations and forms of treatments. Practical sessions are planned to give students the opportunity to expose their knowledge for discussion and confirm concepts learned in lectures. Small group discussions of clinical cases are planned at the end of the course were students are divided into small groups and with the help of an instructor they analyze and discuss the problem. The course will be given through 28 lectures, 7 practical (laboratory) sessions, and one small group discussion activity over 15 weeks and for one whole semester. -
1 Pathology Week 1 – Cellular Adaptation, Injury and Death
Pathology week 1 – Cellular adaptation, injury and death Cellular responses to injury Cellular Responses to Injury Nature and Severity of Injurious Stimulus Cellular Response Altered physiologic stimuli: Cellular adaptations: • ↑demand, ↑ trophic stimulation (e.g. growth factors, hormones) • Hyperplasia, hypertrophy • ↓ nutrients, stimulation • Atrophy • Chronic irritation (chemical or physical) • Metaplasia Reduced oxygen supply; chemical injury; microbial infection Cell injury: • Acute and self-limited • Acute reversible injury • Progessive and severe (including DNA damage) • Irreversible injury → cell death Necrosis Apoptosis • Mild chronic injury • Subcellular alterations in organelles Metabolic alterations, genetic or acquired Intracell accumulations; calcifications Prolonged life span with cumulative sublethal injury Cellular aging Hyperplasia - response to increased demand and external stimulation - ↑ number cells - ↑ volume of organ - often occurs with hypertrophy - occurs if cells able to synthesize DNA – mitotic division - physiologic or pathologic Physiological hyperplasia A) hormonal – ↑ functional capacity tissue when needed (breast in puberty, uterus in pregnancy) B) compensatory - ↑ tissue mass after damage/resection (post-nephrectomy) Mechanisms: - ↑ local production growth factors or activation intracellular signaling pathways o both → production transcription factors that turn on cellular genes incl those encoding growth factors, receptors for GFs, cell cycle regulators →→ cellular proli feration - in hormonal hyperplasia -
Hyperplasia (Growth Factors
Adaptations Robbins Basic Pathology Robbins Basic Pathology Robbins Basic Pathology Coagulation Robbins Basic Pathology Robbins Basic Pathology Homeostasis • Maintenance of a steady state Adaptations • Reversible functional and structural responses to physiologic stress and some pathogenic stimuli • New altered “steady state” is achieved Adaptive responses • Hypertrophy • Altered demand (muscle . hyper = above, more activity) . trophe = nourishment, food • Altered stimulation • Hyperplasia (growth factors, . plastein = (v.) to form, to shape; hormones) (n.) growth, development • Altered nutrition • Dysplasia (including gas exchange) . dys = bad or disordered • Metaplasia . meta = change or beyond • Hypoplasia . hypo = below, less • Atrophy, Aplasia, Agenesis . a = without . nourishment, form, begining Robbins Basic Pathology Cell death, the end result of progressive cell injury, is one of the most crucial events in the evolution of disease in any tissue or organ. It results from diverse causes, including ischemia (reduced blood flow), infection, and toxins. Cell death is also a normal and essential process in embryogenesis, the development of organs, and the maintenance of homeostasis. Two principal pathways of cell death, necrosis and apoptosis. Nutrient deprivation triggers an adaptive cellular response called autophagy that may also culminate in cell death. Adaptations • Hypertrophy • Hyperplasia • Atrophy • Metaplasia HYPERTROPHY Hypertrophy refers to an increase in the size of cells, resulting in an increase in the size of the organ No new cells, just larger cells. The increased size of the cells is due to the synthesis of more structural components of the cells usually proteins. Cells capable of division may respond to stress by undergoing both hyperrtophy and hyperplasia Non-dividing cell increased tissue mass is due to hypertrophy. -
Section XI Extraskeletal (Ectopic) Calcification and Ossification
Section XI Extraskeletal (Ectopic) Calcification and Ossification Michael P. Whyte Division of Bone and Mineral Diseases, Washington University School of Medicine at Barnes-Jewish Hospital and Center for Metabolic Bone Disease and Molecular Research, Shriners Hospitals for Children, St. Louis, Missouri INTRODUCTION somewhat higher value because they have greater serum phos- phate concentrations compared with adults. However, this is A significant number and variety of disorders cause extraskel- not well established.(5) etal deposition of calcium and phosphate (Table 1). In some, The material that comprises metastatic calcification may be mineral is precipitated as amorphous calcium phosphate or as amorphous calcium phosphate initially, but hydroxyapatite is crystals of hydroxyapatite; in others, osseous tissue is formed. deposited soon after.(2) The anatomic pattern of deposition The pathogenesis of ectopic mineralization is generally attrib- varies somewhat between hypercalcemia and hyperphos- uted to one of three mechanisms (Table 1). First, a supranormal phatemia, but occurs irrespective of the specific underlying “calcium-phosphate solubility product” in extracellular fluid condition or mechanism for the disturbed mineral homeostasis. can cause metastatic calcification. Second, mineral may be Additionally, there is a predilection for certain tissues. deposited as dystrophic calcification into metabolically im- Hypercalcemia is typically associated with mineral deposits paired or dead tissue despite normal serum levels of calcium in the kidneys, lungs, and fundus of the stomach. In these and phosphate. Third, ectopic ossification (or true bone forma- “acid-secreting” organs, a local alkaline milieu may account tion) occurs in a few disorders for which the pathogenesis is for the calcium deposition. In addition, the media of large becoming increasingly understood. -
Cellular Adaptation
Cellular Adaptation Dr. Adeboye OO (MBBS, Cert. LMIH, FMCPath) Dept of Anatomic Pathology Bowen University Cellular adaptation • Cell death is not the only consequence of cellular injury or stress • Cells can respond to excessive physiologic or pathologic stimuli by undergoing both functional and morphologic change in which a new steady state is achieved that preserves the viability of the cell(Adaptation) . • The adaptive response include- • Adaptation of growth and differentiation • Intracellular accumulation • Pathologic calcification • Hyaline change • Cellular aging Adaptation of growth and differentiation • Adaptations are reversible changes in the size, number,phenotype, metabolic activity, or functions of cells in response to changes in their environment. Such adaptations may take several distinct forms : • 1. hyperplasia • 2. hypertrophy • 3. atrophy • 4. metaplasia hypertrophy • Increase in the size of cells that result in the increase in size of the affected organ. • No new cells just larger cells • May coexist with hyperplasia in cells capable of division( eg epithelial, hematopoesis etc), in non dividing cells (eg the nerve ,cardiac and skeletal muscle) increase tissue mass is due to hypertrophy • Can be physiologic or pathologic Physiologic hypertrophy • Caused by- (a) increased functional demand eg hypertrophy of striated muscle in muscle builder.(b) stimulation by hormones or growth factors eg physiologic hypertrophy of the uterus during pregnancy Hypertrophy of uterus during pregnancy Micrograph showing smooth muscle -
Tissue Engineering Strategies to Improve Tendon Healing and Insertion Site Integration
Tissue Engineering Strategies to Improve Tendon Healing and Insertion Site Integration A dissertation submitted to the Division of Research and Advanced Studies of the University of Cincinnati in partial fulfillment of the of the requirements for the degree of DOCTOR OF PHILOSOPHY (Ph.D.) in the Department of Biomedical Engineering of the College of Engineering and Applied Science 2011 by Kirsten Rose Carol Kinneberg B.S., University of Minnesota, Twin Cities, MN, 2006 Committee Chair: Jason T. Shearn Abstract Tendon and ligament tears and ruptures remain common and significant musculoskeletal injuries. Repairing these injuries continues to be a prominent challenge in orthopaedics and sports medicine. Despite advances in surgical techniques and procedures, traditional repair techniques maintain a high incidence of re-rupture. This has led some researchers to consider using tissue engineered constructs (TECs). Previous studies in our laboratory have demonstrated that TEC stiffness at the time of surgery is positively correlated with repair tissue stiffness 12 weeks post-surgery. This correlation provided the rationale for implanting a soft tissue patellar tendon autograft (PTA) to repair a central-third defect in the rabbit patellar tendon (PT). The PTA was significantly stiffer than previous TECs and matched the stiffness of the normal central-third PT. Accordingly, we expected a significant improvement in repair tissue biomechanics relative to both natural healing (NH) and TEC repair. At 12 weeks, treatment with PTA improved repair tissue stiffness relative to NH. However, PTA and NH tissues did not differ in maximum force, modulus or maximum stress. Additionally, neither repair group regenerated normal zonal insertion sites. -
Seventh Congress of the International Bioiron Society (IBIS)
Seventh Congress of the International BioIron Society (IBIS) Biennial World Meeting (BioIron 2017) May 7 – 11, 2017 UCLA Meyer & Renee Luskin Conference Center | Los Angeles, USA Featuring Special Events: Introductory Course – May 7, 2017 “Essentials of BioIron for Clinicians and Scientists” “Meet the Expert” Sessions for Trainees May 10 – 11, 2017 INTERNATIONAL BIOIRON SOCIETY PROGRAM BOOK Acknowledgments IBIS This conference has received support from the NIH NCATS UCLA CTSI Grant Number UL1TR0001881. This conference has received support from the NIH/NIDDK R-13 Grant. This conference has received support from the NIXHNHLBI-R-13 Grant. Seventh Congress of the International BioIron Society Page 2 Table of Contents IBIS Seventh Congress of the Internationl BioIron Society (IBIS) Biennial World Meeting (BioIron 2017) May 7 - 11, 2017 UCLA Meyer & Renee Luskin Conference Center | Los Angeles, USA Welcome Message ..............................................................................................................................Page 4 Board of Directors ................................................................................................................................Page 5 General Meeting Information ...............................................................................................................Page 6 Special Events .....................................................................................................................................Page 8 Local Activities .....................................................................................................................................Page -
Acquired Tumors Arising from Congenital Hypertrophy of the Retinal Pigment Epithelium
CLINICAL SCIENCES Acquired Tumors Arising From Congenital Hypertrophy of the Retinal Pigment Epithelium Jerry A. Shields, MD; Carol L. Shields, MD; Arun D. Singh, MD Background: Congenital hypertrophy of the retinal lacunae in all 5 patients. The CHRPE ranged in basal di- pigment epithelium (CHRPE) is widely recognized to ameter from 333mmto13311 mm. The size of the el- be a flat, stationary condition. Although it can show evated lesion ranged from 23232mmto83834 mm. minimal increase in diameter, it has not been known to The nodular component in all cases was supplied and spawn nodular tumor that is evident ophthalmoscopi- drained by slightly prominent, nontortuous retinal blood cally. vessels. Yellow retinal exudation occurred adjacent to the nodule in all 5 patients and 1 patient developed a second- Objectives: To report 5 cases of CHRPE that gave rise ary retinal detachment. Two tumors that showed progres- to an elevated lesion and to describe the clinical features sive enlargement, increasing exudation, and progressive of these unusual nodules. visual loss were treated with iodine 125–labeled plaque brachytherapy, resulting in deceased tumor size but no im- Methods: Retrospective medical record review. provement in the visual acuity. Results: Of 5 patients with a nodular lesion arising from Conclusions: Congenital hypertrophy of the retinal pig- CHRPE, there were 4 women and 1 man, 4 whites and 1 ment epithelium can spawn a nodular growth that slowly black. Three patients were followed up for typical CHRPE enlarges, attains a retinal blood supply, and causes exuda- for longer than 10 years before the tumor developed; 2 pa- tiveretinopathyandchroniccystoidmacularedema.Although tients were recognized to have CHRPE and the elevated no histopathologic evidence is yet available, we believe that tumor concurrently. -
Cellular Adaptation
ALTERATIONS IN CELLULAR AND TISSUE FUNCTION Lois E. Brenneman, MSN, APN, CELLULAR ADAPTATION Atrophy - decrease or shrinkage in cell size - Can (if sufficient numbers) result in shrinkage of entire organ Example: muscular atrophy after cast is removed Example: sports steroid abuse causes atrophy of penis - Physiologic atrophy - normal process Example: atrophy of thymus during childhood - Pathologic atrophy - disease process Example: Addison’s disease -> atrophy adrenal glands - Disuse Atrophy Example: Prolonged bed rest causes muscle atrophy Example: Casting limb causes atrophy Atrophic cells have fewer mitochondria and myofilaments Autophagic vacuoles occurs with malnutrition Lipofuscin - yellow-brown age pigment (may resist destruction) - Persists as membrane-bound residue bodies - Accumulates w age: liver, myocardial and atrophic cells - Results in “age spots” to skin “Age spots” Lipofuscin accumulation to skin © 2004 Lois E. Brenneman, MSN, CS, ANP, FNP all rights reserved - www.npceu.com 1 Hypertrophy - increase in cell size (vs cell number with hyperplasia) Results in increased size of organ Cardiac and kidney esp prone to hypertrophy Increased size -> increased cellular protein and not increased fluid Physiologic hypertrophy - normal process Example: muscle increase with exercise Example: genital size increase with hormones of puberty Pathologic hypertrophy - disease process Example - Left ventricular hypertrophy from hypertension -> congestive heart failure Triggers for hypertrophy Mechanical: stretch, exercise Trophic: growth factors, hormones, vasoactive agents CELLULAR HYPERTROPY Left: dependent edema in CHF Right: dilated cardiomyopathy Left ventricular hypertrophy (bottom) vs normal (top) © 2004 Lois E. Brenneman, MSN, CS, ANP, FNP all rights reserved - www.npceu.com 2 Hyperplasia - increase in number of cells (increased rate of cell division) - Can occur in response to injury esp with cell death - Can occur together with hypertrophy note: if organ with non-dividing cells (e.g.