Presentation on theme: "Intro to Pathology. The study of the origin and development of disease Pathologists investigate etiology and pathogenesis By way of morphology (morphe."— Presentation transcript:
The study of the origin and development of disease Pathologists investigate etiology and pathogenesis By way of morphology (morphe = form) Using techniques of histology (histo = tissue) as well as biochemistry and molecular biology With goal of easing clinical signs and symptoms Where the clinician begins
Language Pathos = suffering, feeling Logos = study Genesis = origin, birth, development Eti from aeiti = cause Medical terms are compounded from prefixes, roots, and suffixes that are frequently Greek or Latin Who speaks classic, dead languages? Not your patients, but you will
Comprehend and deduce There are a lot of terms to “memorize” There are patterns in the usage of the language Learn the meaning of the parts of the language Recognize the patterns, decode the terms, deduce the importance of their meaning Back-translate to your patient, recalling when it was “all Greek to you”
Pattern recognition and language comprehension Elements of recognition Emergence Invariance Elements of comprehension Greek and Latin terminology Prefix, root, suffix
Case study: What does it mean, “Toll-like” receptor? What language? English, toll = fee for use, usually when crossing a bridge or travelling on a restricted-access road. German, toll = crazy, weird, awesome, … What usage? Exclamation! Upon discovering a mutant drosophila that was all back and no front. Toll is a maternal-dominant gene that controls segmentation and body plan patterning during embryonic development in flies Toll is a receptor that provides protection from fungal infection in adult flies
Does comprehending the name help understand the function? Maybe not, but there is still a pattern Toll-like receptors share primary (sequence), secondary (domain), tertiary (chain folding), and quaternary (protein-protein association) structure with the IL-1 receptor superfamily Recognized patterns of amino acid sequence and folded shapes led to discovery of functional homologs from nematode to human—even fungal resistance in plants Innate immunity as opposed to adaptive immunity is a concept with a foundation in discovery of TLRs Pathogenic strains of E.coli secrete proteins that mimic the tertiary structure of TLRs, blocking signal transduction and enhancing survival of the bacteria. Toll!
Start with cellular alterations Rudolf Virchow, the father of modern pathology, pioneered the use of microscopes in modern (mid 1800s) medical education “Omnis cellula e cellula” every living cell arises from a prexisting living cell Disease caused by patterns of injuries (lesions) to cells, extracellular matrix, tissue, organ, person
Mechanisms of muscle hypertrophy Increased protein synthesis increased cell size increased organ size Nondividing cells produce more protein and membrane without division Mechanosensors, PI3K /Akt signaling pathway important in exercise-induced growth Growth factors, vasoactive agents, hormones mediate stress-induced response Unrelieved stress eventually results in irreversible injury
PI(3)K/Akt cascade promotes hypertrophy downstream of IGF-1
Pathological hormomal hyperplasias Hyperplasias reversible with appropriate treatment Benign Prostate Hyperplasia BPH from accumulation of stable DHT-AR complexes Androgen-driven upregulation of Fibroblast Growth Factors and TGFb FGF stimulates proliferation of stroma Goiters Endemic—dietary iodine deficieny or goitrogen ingestion Production of T3 and T4 inhibited Feedback inhibition of TRH and TSH relieved Over-stimulation of thyroid by TSH Hyperplasia often nodular Euthyroid to hypothyroid metabolic status Grave’s disease Autoimmune stimulation of TSH receptor by an IgG Production of T3 and T4 stimulated Diffuse hyperplasia Hyperthyroid metabolic status
Epithelial dysplasia This is cellular dysplasia in the uterine cervix. The normal cervical squamous epithelium has become transformed to a more disorderly growth pattern, or dysplastic epithelium. This is farther down the road toward neoplasia, but dysplasia is still a potentially reversible process.
Metaplasia respiratory epithelium Metaplasia of laryngeal respiratory epithelium has occurred here in a smoker. The chronic irritation has led to an exchanging of one type of epithelium (the normal respiratory epithelium at the right) for another (the more resilient squamous epithelium at the left). Metaplasia is not a normal physiologic process and may be the first step toward neoplasia
Metaplasia of esophageal epithelium Glandular, or Barrett’s,metaplasia of the normal esophageal squamous mucosa has occurred here, with the appearance of gastric type columnar mucosa, secondary to gastric reflux.
Gonadal hypoplasia Gonadal hypoplasia secondary to hypothalamic deficiency of Gonadotropin Releasing Hormone, which results in deficient release of LH and FSH from the pituitary. Called adiposogenital syndrome, Frölich's syndrome, or hypothalamic eunuchism
Hypoplastic lung Microscopic examination of the lung reveals no alveolar development, only tubular bronchioles incapable of significant gas exchange, in this premature baby with pulmonary hypoplasia from oligohydramnios. This results in insufficient gas exchange from respiration following birth.
Muscle fiber atrophy Some of these skeletal muscle fibers here show atrophy, compared to normal fibers. The number of cells is the same as before the atrophy occurred, but the size of some fibers is reduced. This is a response to injury by "downsizing" to conserve the cell. In this case, innervation to the small, atrophic fibers was lost. (This is a trichrome stain.)
Mechanisms of cell injury Energy depletion (ATP) Mitochondrial permeability Cytosolic calcium increase Free radicals, reactive (activated) oxygen species (ROS) Membrane damage and permeability changes DNA and protein structural damage