Cell Injury And Adaptation - PDF

VPA: 5341 CELL INJURY AND ADAPTATION Dr Georgios Paraschou DVM, DACVP, DipRCPath, MRCVS Modified from Dr Tabaran, Dr. Pompei Bolfa Dr. María José Navarrete Talloni, Dr. Allan Kessel Overview of the lecture 1. Normal Cell and Homeostasis 2. Cell adaptation  2.1 Atrophy  2.2. Hypertrophy  2.3. Hype...

VPA: 5341 CELL INJURY AND ADAPTATION Dr Georgios Paraschou DVM, DACVP, DipRCPath, MRCVS Modified from Dr Tabaran, Dr. Pompei Bolfa Dr. María José Navarrete Talloni, Dr. Allan Kessel Overview of the lecture 1. Normal Cell and Homeostasis 2. Cell adaptation  2.1 Atrophy  2.2. Hypertrophy  2.3. Hyperplasia  2.4. Metaplasia  2.5. Dysplasia Normal Cell Smallest section of a living animal Review your histology notes and your pathology textbook. We encourage you to watch http://www.youtube.com/w atch?v=1IqsE8CVTms Cell adaptation ►Occurs when the cell homeostasis is distorted by stress or pathologic stimuli Robbins and Cotran pathologic basis of disease, 8th edition Homeostasis Homeo (Gr.): for similar, like, resembling Stasis (Gr.): stay Definition: tendency to stability in the normal body states of the organism = the ability to maintain internal equilibrium by adjusting its physiological processes Cell adaptation:     In this stage: cells preserve viability and function It is a reversible change The adaptation may be physiologic(al) (normal) or pathologic(al) (abnormal). Five minor types of adaptation include atrophy, hypertrophy, hyperplasia, dysplasia, and metaplasia. Cell adaptation: Hypertrophy Normal cell Atrophy Metaplasia Hyperplasia Overview of the lecture 1. Normal Cell and Homeostasis 2. Cell adaptation  2.1 Atrophy  2.2. Hypertrophy  2.3. Hyperplasia  2.4. Metaplasia  2.5. Dysplasia 2.1.Atrophy Decrease in size and/or number of the cells and their metabolic activity after normal growth has been reached Cells are not dead http://quizlet.com/2336647/skeletal-muscle-flash-cards/ http://www.sciencesway.com/vb/t9961.html#post67288   ↓ Protein synthesis and ↑protein degradation in cells Causes: ▪ ↓ workload ▪ denervation ▪ ↓ blood supply or oxygen ▪ inadequate nutrition ▪ loss of endocrine stimulation ▪ aging (Senescence) http://i.quizlet.net/i/hzq0UbOkT3WyK5FBNBwrTA_m.jpg Atrophy FYI: atrophy of the dorsal and lateral cricoarytenoid muscles (abductor and adductor of the arytenoid cartilage), particularly on the left side. Muscular atrophy is most commonly caused by a primary denervation (recurrent laryngeal neuropathy) of unknown cause (idiopathic axonopathy) and to a much lesser extent, secondary nerve damage laryngeal atrophy Atrophy Examples:  Muscle disuse in a limb that is in a cast  Sedentary atrophy    Atrophy of adrenal cortex by reduction of ACTH stimulation (steroid therapy) Atrophy in tissues adjacent to a tumor due to pressure and compromised blood supply Physiologic atrophy (eg: non-lactating mammary gland, post partum uterus) Atrophy Examples: Normal brain of a young adult. B, Atrophy of the brain in an 82-year-old male with atherosclerotic cerebrovascular disease, resulting in reduced blood supply. Note that loss of brain substance narrows the gyri and widens the sulci. The meninges have been stripped from the right half of each specimen to reveal the surface of the brain. Atrophy Examples: Abnormal http://www.vet.uga.edu/ivcvm/courses/VPAT5200/02_injury/atrophy Normal Atrophy Examples: Serous atrophy of fat F28449 Noah’s archive Atrophy Examples: Serous atrophy of fat Normal http://www.mightysweet.com/mesohungry/wp-content/uploads/2009/12/06-Ham-Bone-Marrow1.jp http://cueflash.com/decks/DMP_715_Path_Exam_1_Necropsy https://veteriankey.com/bone-marrow-blood-cells-and-thelymphatic-system/ Atrophy Examples: Hydrocephalus with compression atrophy, cat Hypoplasia vs atrophy. Never achieved full size vs decreased size due to decrease in cell number     ATROPHY = a diminution in the size of a cell, tissue, organ, or part that was properly developed (Dorland 175) HYPOPLASIA = incomplete development or underdevelopment of an organ or tissue; it is less severe in degree than aplasia. It is a congenital condition (Dorland 905) APLASIA = lack of development of an organ or tissue (Dorland 116) HYPOTROPHY = ABIOTROPHY = progressive loss of vitality of certain tissues or organs, leading to disorders or loss of function; applied especially to degenerative hereditary diseases of late onset Overview of the lecture 1. Normal Cell and Homeostasis 2. Cell adaptation  2.1 Atrophy  2.2. Hypertrophy  2.3. Hyperplasia  2.4. Metaplasia  2.5. Dysplasia 2.2.Hypertrophy  Increased size of cells often leading to increased tissue/organ size ▪  Synthesis of more organelles and structural proteins: bigger cells More common in cells with little replication ▪ Stable cells (bone, cartilage, and smooth muscle) or permanent cells (neurons and cardiac and skeletal muscle myocytes) – less common in labile cells (epidermis, intestinal epithelium, and bone marrow cells) Normal Uterus ??????? Tissues from dogs Hypertrophic Pregnant uterus http://www.pet-informed-veterinary-advice-online.com/spaying-a-pregnant-cat.html Examples of Physiologic Hypertrophy Normal Uterus http://www.pet-informed-veterinary-advice-online.com/spaying-a-pregnant-cat.html Smooth Muscle Hypertrophy Tissues from dogs Pregnant uterus Physiologic hypertrophy: weightlifter Hypertrophy: Mechanisms Robbins and Cotran pathologic basis of disease, 8th edition Hypertrophy Hypertrophy Anterior view of a normal (210 g) heart. Posterior view of a normal (210 g) heart. 24 Posterior view of a hypertrophic (900 g) heart (A) Scale bar = 4cm. http://www.nature.com/ Anterior view of a hypertrophic (900 g) heart. Hypertrophy Cardiac hypertrophy (different causes/mechanisms) limit beyond which enlargement of muscle mass is no longer able to cope with the increased burden →several regressive changes occur in the myocardial fibers ( e.g. lysis and loss of myofibrillar contractile elements) extreme cases →myocyte death Cardiac hypertrophy from hypertension or aortic valve disease http://www.moondragon.org/health/graphics/cardiomegaly.jpg Pathologic Hypertrophy examples: DCM HCM 23 Pathologic Hypertrophy -heart Pathologic Hypertrophy examples: 27 http://www.vetga.com.au/felinediseaselist/felinediseaselist.html FYI – (You will use this info for cardiovascular pathology)  “Cardiomyopathy” generally used to describe idiopathic primary myocardial disease. In humans nearly all have a genetic basis, and it is very likely so in veterinary medicine; it is subdivided into dilated, hypertrophic, and restrictive ▪ ▪ Dilated cardiomyopathy (DCM) is characterized by dysfunction during systole; most common form in dogs Hypertrophic cardiomyopathy (HCM) is characterized by dysfunction during diastole which causes concentric ventricular hypertrophy without dilatation that is not attributable to other cardiac, vascular, or systemic disease; affected cats are usually middle-aged males  ▪  HCM is the most common cardiac disease in cats; it is a heterogeneous disease with many phenotypes; the cause is not known but there is a familial occurrence in some cat breeds (Main coons, Ragdolls)and in humans HCM is a genetic disease, with several hundred recognized mutations Restrictive cardiomyopathy (RCM) is characterized by normal systolic function with decreased ventricular compliance, which leads to problems with ventricular filling In cats: HCM>RCM>DCM http://www.askjpc.org/vspo/show page.php?id=185 Overview of the lecture 1. Normal Cell and Homeostasis 2. Cell adaptation  2.1 Atrophy  2.2. Hypertrophy  2.3. Hyperplasia  2.4. Metaplasia  2.5. Dysplasia 2.3. Hyperplasia   Increase in the number of cells of an organ often leading to increased size of tissue/organ Cells capable of replication May occur concomitantly with hypertrophy Hyperplasia    Permanent cells, such as neurons and cardiac and skeletal muscle myocytes, have very little capacity to regenerate or become hyperplastic in most situations (+) Stable cells, such as bone, cartilage, and smooth muscle, are intermediate in their ability to become hyperplastic. (++) Physiologic Hyperplasia examples: Hormonal: e.g.: mammary gland during pregnancy Compensatory: hepatectomy e.g.: http://img.dailymail.co.uk/i/pix/2007/05_01/FiveSuckleAP_468x318.jpg Pathologic Hyperplasia: most commonly caused by excessive hormonal or growth factor stimulation Examples: a. Epidermal thickening (repeated irritation)  b. Respiratory mucosa (in viral infections) http://www.vspo.us Normal skin epidermis http://www.vspo.us 37 SCC Epidermal hyperplasia proceeds to dysplasia, carcinoma in situ and invasive squamous cell carcinoma Gingival hyperplasia http://www.pathwaysvet.com/wp-content/uploads/2010/01/Gingival-hyperplasia.jpg Tissue from a dog MDx FYI: Grossly, gingival hyperplasia can be indistinguishable from an epulis. Epulis is a nonspecific term that designates a growth of the gingiva. The several kinds of epulides can only be distinguished by histopathologic examination Hyperplasia Affected whippet Normal whippet Markedly increased muscle mass – Cause ?????? Myostatin : protein produced my myocytes that inhibits myocyte growth differentiation and growth Whippets can have a mutation of the myostatin gene which involves a two-base-pair deletion, and results in a truncated, inactive, myostatin protein Bully Whippet …double muscling Congenital muscular hyperplasia ("double muscling") is a genetic disease causing a congenital anatomic skeletal muscle defect (increased number of myofibers) in cattle, dogs, and children. This disorder is caused by defects in the myostatin gene, which controls in utero muscle development. HOMEWORK 1.What is the difference between Atrophy, Hyperplasia and hypertrophy? 2.What do these processes have in common? Overview of the lecture 1. Normal Cell and Homeostasis 2. Cell adaptation  2.1 Atrophy  2.2. Hypertrophy  2.3. Hyperplasia  2.4. Metaplasia  2.5. Dysplasia 2.4. Metaplasia  Change in phenotype of a differentiated cell  Response to chronic irritation  cell withstand stres  May result in ↓ functions or ↑ propensity for malignant transformation (neoplasia)  Reversible if cause is removed  Most often in epithelial cells Metaplasia Examples    Chronic irritation in lungs Vit-A deficiency Estrogen toxicity In mammary tumors *not always an easy gross diagnosis, mainly histo Textbook: page 36 4th edition, Page 29 5th edition Robbins and Cotran pathologic basis of disease, 8th edition  Tracheal Mucosa Tissue : Chicken Oesophagus Process: metaplasia Morphological Description: severe multifocal mucous gland squamous metaplasia Aetiology : Vit A deficiency FYI: Benign mixed tumor in canine mammary gland presenting chondroid and myeloid metaplasia Veterinary Medicine International Volume 2012 (2012), Article ID 274608, Overview of the lecture 1. Normal Cell and Homeostasis 2. Cell adaptation  2.1 Atrophy  2.2. Hypertrophy  2.3. Hyperplasia  2.4. Metaplasia  2.5. Dysplasia 2.5.Dysplasia  Refers to abnormal development ▪  ‘‘alteration in its shape, size, and organization, usually affecting the epithelium, occasionally associated with neoplastic transformation” Mostly of epithelial Term mostly used in neoplastic processes ▪ Near-synonym: “Carcinoma in situ” http://www.colposcopy.org.uk/images/dysplasia.jpg Dog, liver Steven Scott, Western College of Veterinary Medicine University of Saskatchewan, PIGI Group A. Atrophy B. Hyperplasia C. Hypertrophy D. Metaplasia E. Dysplasia Dog, MDX: Hepatocellular carcinoma with nodular hyperplasia Steven Scott, Western College of Veterinary Medicine University of Saskatchewan, PIGI Group Hepatic nodular hyperplasia, liver dog. a) Nodule protrudes above the surface of the adjacent, normal parenchyma. b) Nodular hyperplasia, cut surface. Two hyperplastic nodules are shown. c) Hyperplastic nodule compresses adjacent hepatocytes and can be prominently vacuolated. HE Cat, skin A. Atrophy B. Hyperplasia C. Hypertrophy D. Metaplasia E. Dysplasia Cat, skin MDx: Hyperplasia Thank you!