Lecture 1 Cell Adaptation, Injury & Death

Dr. Nabila Hamdi

MD, PhD

B3.114 nabila.hamdi@guc.edu.eg

For course materials, please visit PBT website

http://pbt.guc.edu.eg

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Course Structure

Assessment

Methods Weight

Quizzes (best 2 out of 3) 20%

Assignments 5%

Mid-term exam 30%

Final exam 45%

The midterm and final exams are computer based-case oriented

problems

6th semester

Pathology & Histology PHTX 621

Cell Injury Inflammation Tissue Healing & Repair Immune Disorders Neoplasia

Course Topics:

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How to study?

Lectures

Tutorials

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evelivesey.deviantart.com

Basic Science Cell, molecule

Clinical Practice Symptoms/Signs

Etiology (Cause)

Pathogenesis (Mechanism)

Pathology is the study of suffering

pathos logos

What is Pathology?

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ILOs • Describe the major mechanisms whereby most injurious agents exert their effects

• Understand the examples of cell injury stated in this lecture, including their causes

and mechanisms

• Describe cell changes that occur with atrophy, hypertrophy, hyperplasia and

metaplasia, and state general conditions under which these changes occur

• State and discuss patterns of reversible/irreversible cell injury

• Differentiate cell death associated with apoptosis and necrosis

• Recognize the different patterns of necrosis

• Compare the pathogenesis of dystrophic and metastatic calcifications

• Understand subcellular responses and autophagy

• Define intracellular accumulations and cite examples

• Understand the process of aging 6

Outline I. Overview

II. Cellular Adaptation to Injury

1. Atrophy

2. Hypertrophy

3. Hyperplasia

4. Metaplasia

III. Causes of Cell Injury

IV. Morphology of Cell & Tissue Injury

1. Reversible injury

2. Necrosis/Apoptosis

3. Patterns of Tissue Necrosis

V. Mechanisms of Cell Injury

VI. Autophagy

VII. Intracellular Accumulations

VIII. Pathologic Calcifications

IV. Ageing

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Overview

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http://ww2.odu.edu/~czemlin/heartattacks.html

Ischemia

Necrosis

Increased load

Hypertension Aortic valve stenosis

Myocardial infarction

Hypertrophy

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Normal/adapted/injured cardiomyocyte

Normal myocyte

Cellular Adaptation to Stress Atrophy

Shrinkage in the size of the cell by the loss of cell substance.

When a sufficient number of cells is involved, the entire tissue or organ diminishes in size, becoming atrophic.

Although atrophic cells may have diminished function, they are not dead.

Causes include decreased workload (immobilization), loss of innervation, decreased blood supply, inadequate nutrition, loss of endocrine function and aging.

Mechanisms include both decreased protein synthesis and increased protein degradation.

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Cellular Adaptation to Stress Atrophy

Aging (senile atrophy). 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.

Loss of endocrine stimulation of the uterus after menopause

Physiologic Atrophy

Brain atrophy Uterus atrophy

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Cellular Adaptation to Stress Atrophy

Loss of innervation (Carpal tunnel syndrome)

Pathologic Atrophy

A Practical Guide to Clinical Medicine, University of California, San Diego

Immobilization of a limb (after fracture)

source: http://soopastank.wordpress.com

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Cellular Adaptation to Stress Atrophy

Pathologic Atrophy

Inadequate nutrition

http://emedicine.medscape.com/article/932104-clinical

Dr. Drew on Angelina Jolie: ‘I see malnutrition’ Celebs, By Dan Schenek,

Diminished blood supply

Constriction of proximal portion of renal artery with ischemic atrophy of the involved kidney

http://www.pathology.vcu.edu/education/PathLab/pages/renalpath/rpsr/images/ras_sr/

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Cellular Adaptation to Stress Hyperplasia

Characterized by an increase in cell number.

It takes place if the cell population is capable of replication.

It can be physiologic or pathologic.

Most forms are caused by excessive hormonal or growth factor stimulation.

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Cellular Adaptation to Stress Hyperplasia

Hormonal hyperplasia Compensatory hyperplasia

Female breast in puberty and pregnancy Liver regeneration after lobar resection

http://whydetox.net/liver-detoxification

Physiologic Hyperplasia

Growth and development of the breast during pregnancy. Ducts and glands undergo marked hyperplasia in preparation for lactation. Ductal proliferation is predominantly controlled by estrogen (E), whereas gland

differentiation is a progesterone (P) effect facilitated by estrogen.

The Breast During Pregnancy and Lactation, Julia V. Johnson and Daniel H. Riddick

Mitotic activity in the remaining cells begins as early as 12 hours later, eventually restoring the liver to its normal weight

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Cellular Adaptation to Stress Hyperplasia

Pathologic Endometrial Hyperplasia

Excessive hormonal stimulation

(leads to abnormal menstrual bleeding)

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Physiologic Hyperplasia during normal

menstrual cycle

Cellular Adaptation to Stress Hyperplasia

Renal cell carcinoma often secrete erythropoietin, the hormone stimulates the growth of erythrocyte precursors in the bone marrow

Pathologic Hyperplasia

Bone marrow hyperplasia Papillomaviruses cause skin warts

(Virus-induced growth factor stimulation)

Incidence of Kidney Cancer Increasing October 29, 2009 · By ASHISH V. DALAL, M

Erythropoietin

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Cellular Adaptation to Stress Hypertrophy

Hypertrophy is an increase in the size of cells resulting in increase in the size of the organ.

There are no new cells, just bigger cells, enlarged by an increased amount of structural proteins and organelles (increase in mRNA and proteins).

It can be physiologic or pathologic and is caused either by increased functional demand or by growth factor or hormonal stimulation.

Occurs when cells are unable to divide (heart & skeletal muscle).

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Cellular Adaptation to Stress Hypertrophy

Myocardial hypertrophy Cross-section of the heart of a patient with long-standing hypertension

shows pronounced, concentric left ventricular hypertrophy.

Cell Injury. David S. Strayer Emanuel Rubin Copyright ©2009 Lippincott Williams & Wilkins

http://aminoacidstudies.org/muscle-growth/

Skeletal muscle hypertrophy (after weightlifting)

Physiologic Hypertrophy Pathologic Hypertrophy 19

Cellular Adaptation to Stress Hypertrophy + Hyperplasia

The massive physiologic enlargement of the uterus during pregnancy occurs as a consequence of estrogen-stimulated smooth muscle hypertrophy and smooth muscle hyperplasia

Gravid uterus

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Cellular Adaptation to Stress Metaplasia

Metaplasia is a reversible change in which one adult cell type is replaced by another adult cell type.

Cells sensitive to a particular stress are replaced by other cell types better able to withstand the adverse environment.

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Cellular Adaptation to Stress Metaplasia

The normal ciliated columnar epithelial cells of the trachea and bronchi are focally or widely replaced by stratified squamous epithelial cells, which has survival advantages.

However, Important protective mechanisms are lost, such as mucus secretion and ciliary clearance of particulate matter.

Metaplasia of normal columnar (left) to squamous epithelium (right) in a bronchus, shown (A) schematically and (B) histologically

Cigarette smoking

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Cellular Adaptation to Stress Metaplasia

Gastroesophageal reflux disease (GERD)

Stuart Jon Spechler, JAMA, August 14, 2013, Vol 310, No. 6

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Cellular Adaptation to Stress

Atrophy, hypertrophy, hyperplasia and metaplasia are reversible changes!

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Case

• On a routine visit to the physician, an otherwise healthy 51-year-

old man has a blood pressure of 150/95 mm Hg. If the patient’s

hypertension remains untreated for years, which of the following

cellular alterations will most likely be seen in the myocardium ?

a) Atrophy

b) Hyperplasia

c) Metaplasia

d) Hemosiderosis

e) Hypertrophy

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References

ROBBINS Basic Pathology 9th Edition ROBBINS Basic Pathology 8th Edition Basic Pathology 7th Edition, by Kumar, Cotran and Robbins Source of the cover cell image http://timothyjoseph.net/kill-or-be-killed/

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