Cell injury Lecture 4-5 Dr Hisham Alkhalidi. Mechanisms of cell deposition, diagram.
Lecture Title: Cell injury
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Transcript of Lecture Title: Cell injury
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LECTURE TITLE: CELL INJURY
Lecturer name: Dr. Maha ArafahLecture Date: 15-9-2012
(Foundation Block, pathology)
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CONCEPT OF INJURY AND CELLULAR RESPONSE TO INJURY
L1: Overview of Cell Injury, adaptation to
environmental stress and Cell Death Free radical injury, types of necrosis and apoptosis
L2: Mechanism of injury, Necrosis and Apoptosis Cellular accumulation and adaptation to injuries
L3: Cellular accumulation and Calcification Pathological calcification
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OVERVIEW OF CELL INJURY AND ADAPTATION
Upon completion of this lecture, the student should know:• Causes of cell injury• Adaptation to stress•Reversible cell injury ( nonlethal hit) • Irreversible injury and cell death ( lethal hit)• Morphology of cell injury
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CONCEPT OF INJURY AND CELLULAR RESPONSE TO INJURY
Cells are constantly exposed to a variety of stresses. When too severe, INJURY results.
Injury alters the preceding normal steady state of the cell.
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ALL CELLS
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ALL ORGANISM
S
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ALL MEDICAL STUDENT
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LIVING IN THE WORLD
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MUST COPE WITH…
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STRESS!!!
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Cellular Responses to Injury
Nature and Severity of Injurious Stimulus
Cellular Response
Altered physiologic stimuli: Cellular adaptations:
Increased demand, increased trophic stimulation (e.g. growth factors, hormones)
Hyperplasia, hypertrophy
Decreased nutrients, stimulation Atrophy
Chronic irritation (chemical or physical) Metaplasia
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The Four Main Types of Cell Adaptations
Atrophy: shrinkage of an organ as a result of decreased cell size (and cell number).Hypertrophy: enlargement of an organ as a result of increased cell size.Hyperplasia: enlargement of an organ through an increase in cell number.Metaplasia: the replacement of one differentiated cell type by another in a tissue or organ.
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Atrophy
Reversible
Decrease in size of cell (-s) previously of normal size
Physiologicshrinkage of testes and
ovaries with age
Pathologic • Decreased function• Loss of innervation• Pressure (“bed soars”)• Malnutrition/cahexia • Loss of endocrine stimulation• Aging
Net results: tissue /organ smaller than normal
Signals/injury
Atrophy Hypoplasia & Aplasia• Developmental failure• Failure in morphogenesis
Autophagy Less organellsReduced metabolic rateLipofuscin granules
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LIPOFUSCIN: wear and tear pigment
Lipofuscin granules are yellow/brown in color and represent non-digestible fragments of lipids and phospholipids combined with protein within autophagic vacuoles. They are commonly seen in ageing liver and myocardial cells.
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Hypertrophy – cell or organ
Reversible
Increase in size of cell in response to increased functional demand and/or in response to Hormone/growth factors stimulation
Physiologic
• Athletes muscle• Pregnant uterus• Prostatic tissue (elderly)
Pathologic • Cardiac muscle
• bladder smooth muscle hypertrophy in outflow obstruction
Net effect: increase in size/volume/weight of tissue / organ
Signals/injury
Occur in cells which cannot divid
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Morphology of hypertrophy Hypertrophic muscle cells show:
Increased membrane synthesis.Increased amounts of ATP.Increased enzyme activity.Increased myofilaments.Hypertrophy of smooth endoplasmic reticulum
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Hyperplasia – cell or organ
Reversible
Increase in number of cells in response to increased functional demand and/or in response to Hormone/Growth Factor stimulation
Physiologic • Uterine muscle in
pregnancy• Lactating breast• Compensatory after
hepatectomy
Pathologic • Endocrine stimulation, e.g. Thyroid• Focal nodular hyperplasia (liver)• Adenomatous hyperplasia of
endometrium
Net effect :increase in size/volume/weight of tissue / organ
Signals/injury
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Endometrial hyperplasia
Endometrial carcinoma endometrial hyperplasia
Can be transformed to endometrial carcinoma
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Signals/injury
Reversible
But not always
Metaplasia
Substitution of mature (differentiated) cell for another mature cell
Physiologic (metaplastic tissue/organs)
• cervical canal
Pathologic (metaplastic tissue/organs)
• Gastric/duodenal metaplasia• Ciliated to squamous in bronchial epith.• Osseous metaplasia• Barret’s oesophagus
Net effect: another cell/tissue - protective – changes in function
genetic "reprogramming" of stem cells
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Metaplasia
Ciliated
Squamous
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Notice Metaplasia is often seen next to
neoplastic epithelium, indicating that although this adaptive response is potentially reversible, continued insult to the cells may cause uncontrolled growth and the development of cancer.
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Etiologic agents
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Causes of cell injury1. DEFICIENCY OF OXYGEN Ischemia
vs. Hypoxia2. PHYSICAL AGENTS3. CHEMICAL AGENTS4. INFECTION5. IMUNOLOGICAL REACTIONS6. GENETIC DERANGEMENTS7. NUTRITIONAL IMBALANCE8. AGING
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Brain – massive haemorrhagic focus (ischemia) in the cortex
This is a lesion caused by
DEFICIENCY OF OXYGEN
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Abscess of the brain (bacterial)
This is a lesion caused by
infectious agent
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This is a lesion caused by
chemical agent
Hepatic necrosis (patient poisoned by carbon tetrachloride)
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Pulmonary caseous necrosis (coccidioidomycosis)
This is a lesion caused by
infectious agent
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Gangrenous necrosis of fingers secondary to freezing
This is a lesion caused by
physical agent
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The “boutonnière” (buttonhole) deformity
This is a lesion caused by
intrinsic factors(autoimmune disease)
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Liver: macronudular cirrhosis (HBV)
This is a lesion caused by
infectious agent:Viral hepatitis
(chemical:alcohol, genetic:a1-AT
deficiency)
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MORPHOLOGY OF CELLS IN REVERSIBLE AND
IRREVERSIBLE INJURY
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myocadial cells: loss of function after 1-2 min of ischemiaHowever do not die until 20 to 30 min of ischemia EM: 2-3 hours, LM 6-12 hours
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Morphologic changes in Reversible Injury
Early changes:(1) Cloudy swelling or hydropic changes: Cytoplasmic
swelling and vacuolar degeneration due to intracellular accumulation of water and electrolytes secondary to failure of energy-dependent sodium pump.
(2) Mitochondrial and endoplasmic reticulum swelling due to loss of osmotic regulation.(3) Clumping of nuclear chromatin.
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Vacuolar (hydropic) change in cells lining the proximal tubules of the kidney
Reversible changes
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Morphologic changes in irreversible injury:
1. Severe vacuolization of the mitochondria, with accumulation of calcium-rich densities.
2. Extensive damage to plasma membranes.
3. Massive calcium influx activate phospholipase, proteases, ATPase and endonucleases with break down of cell component.
4. Leak of proteins, ribonucleic acid and metabolite.
5. Breakdown of lysosomes with autolysis.
6. Nuclear changes: Pyknosis, karyolysis, karyorrhexis.
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IRREVERSIBLE CELL INJURY- NECROSIS
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Morphologic changes in irreversible injury
- Dead cell are either collapsed and form a whorled phospholipid masses or degraded into fatty acid with calcification.- Cellular enzymes are released into circula- tion. This provides important clinical parameter of cell deathe.g. increased level of creatinin kinase in
blood after myocardial infarction
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Myocardial infarct This is a lesion caused by
oxygen deprivation
Cell Pathology
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MECHANISMS OF CELL INJURY General principles:- The cellular response to injurious stimuli depends on 1. type of injury
2. Its duration 3. Severity
-The consequences depend onthe type, status, adaptability, and genetic
makeup of the injured cell.
-The structural and biochemical components of a cell are so integrally connected that multiple
secondary effects rapidly occur
-Cellular function is lost far before cell death occurs
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TAKE HOME MESSAGES: Cell injury is common event and the body
respond by adaptation to a certain limit. Adaptation include atrophy, hypertrophy,
hyperplasia and metaplasia. Cellular injury is caused by various elements
include bacterial toxins, hypoxia, alcohol, viruses and radiation.
Cellular injury could be reversible (sublethal) or irreversible (lethal).
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Dr. Maha Arafah15-9-2011
(Foundation Block, pathology)
THANK YOU