Cellular Adaptations PDF

Basic pathology Dr. Mishaal Adaptations & Accumulations  Objectives The students should: - Understand the concept of cells and tissue adaptation to environmental stress including the meaning & types of hypertrophy, hyperplasia, atrophy, hypotrophy and metaplasia wi...

Basic pathology Dr. Mishaal Adaptations & Accumulations  Objectives The students should: - Understand the concept of cells and tissue adaptation to environmental stress including the meaning & types of hypertrophy, hyperplasia, atrophy, hypotrophy and metaplasia with their clinical manifestations. - Understand the causes of and pathologic changes occurring in intracellular and extracellular accumulations of materials causing degenerations. - Understand the causes of and pathologic changes of exogenous and endogenous pigments (e.g. carbon, silica, iron, melanin, bilirubin and lipofuscin), Amyloidosis definition and types, Calcification Definition and types (Dystrophic Calcification & Metastatic Calcification) Adaptations  Cellular Responses Stimulus Cellular Response A) Altered Physiologic: Adaptations Increased demand or stimulation Hyperplasia (increased number cells) (eg., growth factors, hormones) Hypertrophy (increase size cells/organ) Decreased nutrients or Hypoplasia (decreased number of cells) stimulation Atrophy (decrease size cells/organ) Chronic irritation (chemical, Metaplasia (reversible change from one physical, inflammatory) adult cell type to another) B) Injurious agents e.g. reduced Cell Injury O2, infection, chemical toxins Mild acute and self-limited Acute reversible injury Progressive & severe Irreversible injury cell death (including DNA damage) (necrosis or apoptosis) Mild chronic injury and Metabolic Alterations in organelles and Intracellular alterations & extracellular accumulations Cellular Responses  Adaptation Def : Adaptation is reversible functional and structural cell response to stress in which a new steady state is achieved which allows the cell to survive and continue its functions. Cells respond to modest changes (stress and injuries) by functional and structural different types of adaptations. General causes of adaptations : Cells respond to increased work demand and trophic stimulation by hypertrophy or hyperplasia, and they respond to reduced supply of nutrients and growth factors and reduced stimulation by atrophy. In some situations, cells change from one type to another, a process called metaplasia.  Normal Growth & Maturation The cells continue to grow, divide (proliferate) and mature (differentiate) to maintain the normal structure of a particular tissue, adapt to modest stimuli, and repair after injury.  Normal Growth & Maturation Tissue- proliferative activity The type of cells according to heir proliferative activity are divided into three groups: 1. Labile cells: Proliferate continuously e.g.: epithelial cells, haemopoeitic and lymphoid tissue. 2. Stable cells: have the ability to proliferate in certain conditions, e.g.: parenchymal cells of liver, kidney and pancreas, and mesenchymal cells as smooth muscles, fibroblasts and osteoblasts. 3. Permanent cells: These cells do not proliferate e.g.: neurons, skeletal muscles and heart muscles.  Adaptations Hyperplasia : Is the increase in the size of an organ or tissue caused by an increase in the number of cells. *Note: in order for cells to respond with this adaptation, they must be capable of undergoing mitosis through synthesis of DNA (capable of replication), i.e. either labile cells or stable cells. *Note: hypoplasia is not classified as adaptation, but it is a developmental disorder. Hypoplasia is a decrease in the number of cells in an organ or tissue, the term is especially used for congenital inadequate below-average number of cells in an organ, or tissue that has not attained normal maturity.  Types of Hyperplasia Physiologic hyperplasia Pathologic hyperplasia  Types of Hyperplasia Physiologic hyperplasia : Appropriate cellular proliferation to maintain normal function Physiologic hyperplasia are of two types - A- Hormonal hyperplasia e.g. the proliferation of the glands of the female breast at puberty and during pregnancy. - B- Compensatory hyperplasia e.g. when a portion of liver is partially resected, the remaining cells multiply and restore the liver to its original weight.  Hyperplasia: Physiologic Breast lobule, normal 25-year-old female Breast lobule, 25-year-old pregnant female: increase in number of acini within lobule 25-year-old post-partum female: secretory products in apical cytoplasm of epithelial cells; what kind of secretion? Apocrine (lactation) Fig. 25-2, Pathologic Basis of Disease, 6th ed, WB Saunders, 1999.  Types of Hyperplasia Pathologic hyperplasia : Inappropriate cellular proliferation which goes beyond range of normal function, possibly causing signs or symptoms of disease. Examples: endometrial simple hyperplasia, endometrial complex hyperplasia with atypia, breast hyperplasia in fibrocystic disease, benign prostatic hyperplasia  Mechanism: pathologic hyperplasia Causes : most common are : 1- Excessive hormonal stimulation: e.g., Endometrial hyperplasia: – Increased Estrogen – Progesterone/Estrogen imbalance Benign prostatic hyperplasia: – Androgens 2- Excessive growth factor action on target cells : e.g., Skin wart due to viral effect : – Human Papilloma Virus ( HPV ).  Mechanism: pathologic hyperplasia Implications for disease – While pathologic hyperplasia still responds to regulatory control mechanisms, it can cause signs or symptoms of disease, and create more opportunity for acquired mutations that may lead to development of neoplasia Is hyperplasia reversible??? – YES Is hyperplasia premalignant ? – NO…..BUT…patient is at increased risk to develop cancer, such as in Endometrial hyperplasia Prostate Hyperplasia Prostate Hyperplasia  Endometrial Hyperplasia Polipoid endometrium  Endometrial Hyperplasia Endometrium : Cystic endometrial hyperplasia ADRENAL HYPERPLASIA  Pathologic Hyperplasia: Application Top--increased gland density (:Simple Normal hyperplasia)) proliferative Bottom--increased gland density with complex endometrium architecture & nuclear pleomorphism: (Complex hyperplasia with atypia) Endometrial carcinoma and endometrial hyperplasia  Adaptations Hypertrophy : Is an increase in the size of the tissue/organ due to the increase in the size of the cells. Hypotrophy : decrease in size of cells (not commonly used term). Atrophy : decrease in size of cells, or an entire organ(the commonly used term), after attaining its normal mature growth  Adaptations Hypertrophy : Is an increase in the size of the tissue/organ due to the increase in the size of the cells. *Note: Increased cell size is not due to cellular swelling, but to synthesis of more structural components especially intracellular proteins  Types of Hypertrophy Physiologic – Physiological hypertrophy of lactating breast – Massive growth of uterus in pregnancy (hypertrophy and hyperplasia, but mainly hypertrophy of smooth muscles) mediated by estrogen – Skeletal muscles of athletes (increased exercise Increased metabolic demand The cells increase in size. Pathologic – Cardiac concentric left ventricular hypertrophy due to chronic hemodynamic overload (increased work demand); observed in chronic uncontrolled hypertension Physiologic Hypertrophy  Pathologic Hypertrophy Left ventricular hypertrophy  Pathologic Hypertrophy A B NORMAL (350 grams) A- 55 y.o. male with 15 year B- 70 y.o. male with 40 yr. history of essential history of essential hypertension, hypertension, can play tennis short of breath walking up 10 without shortness of breath, steps at home; heart weighs 600 heart weighs 550 grams? grams ? Dilation and Concentric left ventricular hypertrophy (longer hypertrophy (non-dilated) duration hypertension)  Cardiac hypertrophy in hemodynamic overload Fig. 1-4, Pathologic Basis of Disease, 2005 Mechanical: stretch of fibers What are signals that trigger Trophic: peptide growth factors, cardiac myocyte hypertrophy vasoactive agents that increase nutrients and changes in gene expression? for growth of cells  Hypertrophy and hyperplasia Hypertrophy and hyperplasia can occur together, e.g. – the uterus during pregnancy in which there is smooth muscle hypertrophy and hyperplasia. – Lactating breast – Benign prostatic hyperplasia  Adaptations Atrophy: decrease in size of cells, tissue or an entire organ after attaining its normal mature growth. Partial or complete wasting away or progressive decline of a part of the body (tissue or an organ)  Adaptations: Atrophy In medical practice, hormonal and nerve inputs that maintain an organ or body part are said to have trophic effects. A diminished muscular trophic condition is designated as atrophy. Origin of term: Late 16th century: from French atrophier (verb), atrophie (noun), from late Latin atrophia, from Greek a- ‘without’ + trophē ‘food’=‘lack of food’. Or "lack of nourishment". Although the English word doesn't usually imply any lack of food, it always refers to a wasting away  Types of atrophy stimuli Mechanisms and causes: Atrophy may be due to : Physiologic stimuli : e.g. the loss of hormone stimulation in menopause (Loss of endocrine stimulation : atrophy of uterus and breasts in post-menopausal female) Pathologic stimuli : e.g. the loss of denervation, mild chronic ischemia, pressure, disuse, etc... Aging : atrophy of permanent cells in brain and heart in 80 year old person (senile atrophy).  Pathologic causes of atrophy Disuse : loss of skeletal muscle mass with arm in cast for 6 weeks Denervation : traumatic damage to nerve atrophy of muscle fibers supplied Ischaemia : unilateral atrophy of one kidney due to renal artery stenosis Inadequate nutrition. Pressure atrophy. Tissue intrinsic disease.  Adaptations: Atrophy Mechanisms of atrophy: Consist of : - Combination of decreased protein synthesis and increased protein degradation by ubiquitin protease pathway - Increased autophagy by forming autophagy vacuoles Organ or tissue atrophy may be irreversible if permanent cells undergo death by apoptosis Normal Atrophy - testis  Small intestine / atrophy of villi Normal Atrophy Alzheimer disease – brain atrophy  Brain atrophy Normal brain Slide 2.5 W.B. Saunders Company items and derived items Copyright (c) 1999 by W.B. Saunders Company Pathologic atrophy  Adaptations Metaplasia definition : Reversible change in which one mature cell type (epithelial or mesenchymal) is replaced by another mature cell type; typically, the new cell type is better able to withstand a chronic adverse environment. Vitamin A deficiency or excess both can cause metaplasia. Vitamin A deficiency and cigarette smoking induces squamous metaplasia in respiratory epithelium.  Metaplasia Mechanism: reprogramming of stem cells in basal layer of epithelium or of pluripotent mesenchymal cells in connective tissue, causing them to differentiate along a new pathway. Metaplasia is usually reversible provided the causative agent is removed. Persistent stimuli can initiate malignant transformation in metaplastic epithelium such as squamous metaplasia in respiratory epithelium leading to lung squamous cell carcinoma, and squamous metaplasia in the bladder due chronic irritation of schistosoma haematobium eggs leading to bladder squamous cell carcinoma  Metaplasia Types of metaplasia according to affected tissue type: Epithelial metaplasia Mesenchymal metaplasia  Adaptations: Metaplasia Epithelial metaplasia : Squamous metaplasia (multiple sites ; bronchus, endocervix, urinary bladder) Intestinal columnar metaplasia (esophagus, stomach etc…) Gastric columnar metaplasia (esophagus, intestine) Serous or mucinous metaplasia (germinal epithelium of ovary)  Adaptations: Metaplasia Mesenchymal metaplasia : Osseous metaplasia (fibrous scars, areas of calcification) Chondroid metaplasia Myeloid metaplasia  Metaplasia Some important examples include: 1.Squamous metaplasia: 2.Columnar cell metaplasia 3.Osseous metaplasia 4.Myeloid metaplasia  Squamous metaplasia Here columnar cells are replaced by squamous cells. e.g. - In cervix: replacement occurs at the squamoc-olumnar junction. Squamous cell carcinoma of cervix usually arises from the squamous metaplasia in the cervix. - In respiratory tract: the columnar epithelium of the bronchus is replaced by squamous cell following chronic injury in chronic smokers. The squamous epithelium is able to survive under circumstances that the more fragile columnar epithelium would not tolerate. Although the metaplastic squamous epithelium will survive better, the important protective functions of columnar epithelium are lost, such as mucus secretion and ciliary action. If the causative agent persists, it may predispose to malignant transformation. It is thought that cigarette smoking initially causes squamous metaplasia, and later squamous cell cancers arise from it.  Columnar, osseous and myeloid metaplasia 2) Columnar cell metaplasia: it is the replacement of the squamous lining by columnar cells. It is seen in the esophagus in chronic gastro-esophageal reflux disease. The normal stratified squamous epithelium of the lower esophagus undergoes metaplastic transformation to columnar epithelium. This change is called as Barrett’s oesophagus and it can be precancerous and lead to development of adenocarcinoma of esophagus. 3) Osseous metaplasia: it is the formation of new bone at sites of tissue injury. 4) Myeloid metaplasia (extramedullary hematopoiesis): is the proliferation of hematopoietic tissue in sites other then the bone marrow such as liver or spleen. Metaplasia Metaplasia  Metaplasia Clinical significance; Most metaplasia is of little significance. Functional deficits may result in some areas. Dysplastic changes with progression to cancer can occur in metaplastic epithelium. Metaplasia: Applications Normal endocervical mucosa 23 year old female with chronic inflammation of endocervical mucosa: (Squamous metaplasia) Cervical biopsy, 5 years after infection with HPV type 16 or 18: Squamous carcinoma-in- situ (CIN III, cervical intraepithelial neoplasia III) THANKS