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Clinical Pathology
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2. 4/22/2017
Overall Aims of Course
By the end of this course, the students should have a basic pathology knowledge of
structural and functional changes in disease,
what causes disease,
how disease starts, progresses &
how patient signs and symptoms are related to underlying pathology.
This knowledge should provide the students a sound foundation for rational clinical care and therapy and to help student to understand the patient and his disease.
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3. Course Contents Introduction and definitions,
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Course Contents
Introduction and definitions,
Reversible cell injury, Irreversible cell injury,
Intracellular accumulations and extracellular depositions
Growth disturbances
Neoplasia
Circulatory disturbances
Diseases of the heart
Diseases of the respiratory system
Diseases of the upper gastrointestinal tract
Diseases of lower gastrointestinal tract
Diseases of the liver
Diseases of bones and joints
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4. 4/22/2017
Assessment Schedule
Assessment 1… 2 Periodical sheet exams Week beginning from 4th
Assessment 2 … 2 Practical exams Weeks 5 & 10
Assessment 3… Final written exam Week ?
Assessment 4 … Oral exam
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5. Weighting of Assessments
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Weighting of Assessments
Mid-Term Examination % (10 Marks)
Final-term Examination % (50 Marks)
Oral Examination % (15 Marks)
Practical Examination % (25 Marks)
Semester Work
Other types of assessment
Total % (100 Marks)
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6. Recommended Books Recommended Books
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Recommended Books
Recommended Books
Pathologic Basis of Disease, Robbins and Cortran, Elsevier Saunders 8th Edition, 2010
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7. 4/22/2017
PATHOLOGY
Pathology of a disease is formally studied under four subdivisions:
Aetiology - Study of cause / causative agent of disease.
Pathogenesis- Study of disease progression.
Morphology - Study of structural changes in disease (gross & microscopic).
Clinical Significance - Study of how clinical features are related to changes.
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PATHOLOGY
Disease presents with many 'problems' known as symptoms e.g. pain, and with
abnormalities noticed by physician known as signs e.g. abnormal heart sounds.
Finding the nature of disease is known as diagnosis.
Predicting the future course of disease is known as prognosis.
Taking precautions to prevent disease is known as prophylaxis.
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9. 4/22/2017
Cellular Injury
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10. Response to Injury: Adaptations (reversible)
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Response to Injury:
Adaptations (reversible)
Hypertrophy/ increase size of cells
Hyperplasia/ increase no of cells
Atrophy/ decrease in size of cells
Accumulations - protein, fat, etc.
Extracellular calcium deposition
Necrosis (irreversible) – cell death
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11. REVERSIBLE CELL INJURY (DEGENERATION)
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REVERSIBLE CELL INJURY (DEGENERATION)
Functional and morphological changes that are reversible
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12. REVERSIBLE CELL INJURY (DEGENERATION)
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REVERSIBLE CELL INJURY (DEGENERATION)
If the irritant persist, death, necrosis.
Affects parenchymal (metabolically active) cells, such as liver cells, renal tubules more than mesenchymal cells as cardiac muscle.
Causes: reduced oxidative phosphorylation, ATP depletion
cellular swelling caused by changes in ion concentrations and water influx.
Degenerations are mainly due to intracellular accumulation of water or fat.
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13. Types of degeneration:
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Types of degeneration:
Cloudy swelling
Swelling of the cells (due to water accumulation) and granulation of the cytoplasm (due to lipid deposition).
The injurious agents, mainly hypoxia, inhibit oxidative phosphorylation and ATP formation
Fate:
reversible,
if the injury continues, it proceeds to hydropic swelling (reversible) or necrosis.
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14. Normal liver/ Cloudy swelling
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Normal liver/ Cloudy swelling
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15. Types of degeneration:
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Types of degeneration:
Hydropic swelling (Hydropic or vacuolar degeneration):
Excess water accumulation inside the cells forming vacuoles in the cytoplasm. The lesion is more advanced than cloudy swelling.
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16. Hydropic change in ischemic - kidney
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Hydropic change in ischemic - kidney
Microvilli
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17. Types of degeneration:
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Types of degeneration:
3. Fatty change (steatosis):
Small or large lipid vacuoles (neutral lipid) in cyto.
due to the suppression of mitochondrial lipid metabolic enzymes.
Common in liver, heart and kidney
Causes:
hypoxia
bacterial toxins
chemical agents as alcohol, carbon tetrachloride
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18. Fatty change (steatosis)
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Fatty change (steatosis)
Fatty changes in the liver cells are also caused by:
intake of excess dietary fat or starvation.
Diseases / viral hepatitis.
Deficiency of lipotropic factors as choline and methionine accumulation of neutral fat inside the liver cells.
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19. Normal liver/ fatty change (Steatosis)
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Normal liver/ fatty change (Steatosis)
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20. IRREVERSIBLE CELL INJURY (NECROSIS)
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IRREVERSIBLE CELL INJURY (NECROSIS)
Local death of cells or tissues within the living body (irritant).
Necrosis either occurs directly or follows reversible injury.
Necrotic tissue appears opaque/ whitish / swollen.
The surrounding tissue appears red due to inflammatory hyperemia.
Microscopic changes due to lytic action of lysosomal enzymes
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21. 4/22/2017
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22. IRREVERSIBLE CELL INJURY (NECROSIS)
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IRREVERSIBLE CELL INJURY (NECROSIS)
Nuclear changes:
Pyknosis: The nucleus shrinks and stains darkly.
Karyorrhexis: Nuclear fragmentation
Karyolysis: Faint dissolved nucleus.
Cytoplasmic changes: The cells appear homogenous and indistinct from each other.
Architectural changes:
Necrotic tissue structureless due to cell lysis.
Protein denaturation (coagulation) may precede cell lysis.
Necrotic cells preserve the architectural outlines of the original tissue
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23. 22 - Normal cardiac muscle/ coagulative necrosis
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22 - Normal cardiac muscle/ coagulative necrosis
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24. Types of Necrosis: Coagulative Necrosis:
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Types of Necrosis:
Coagulative Necrosis:
Caused by sudden cut of the blood supply (ischemic necrosis)
Denaturation of cellular proteins causing the tissue to appear hard, opaque white and preserves its architecture.
Heart, kidney & spleen
Renal Infarction
Splenic Infarction
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25. Types of Necrosis: Liquefactive Necrosis:
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Types of Necrosis:
Liquefactive Necrosis:
The necrotic tissue is rapidly liquefied. It occurs in:
Infarction of the brain and spinal cord
Pyogenic abscess: The necrotic core is liquefied by the proteolytic enzymes released from pus cells.
Amoebic abscess
Stroke- Liquifactive necrosis
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26. Typical for tuberculous lesions.
TYPES OF NECROSIS
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3. Caseous Necrosis:
Typical for tuberculous lesions.
caseous because the necrotic tissue appears yellowish-white and “cheesy”
Necrosis is followed by slow partial liquefaction.
Architecture is completely obliterated
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27. 4/22/2017
Caseous Necrosis
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28. TYPES OF NECROSIS 4. Fat Necrosis: Enzymatic fat necrosis:
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TYPES OF NECROSIS
4. Fat Necrosis:
Enzymatic fat necrosis:
It occurs in acute hemorrhagic pancreatitis.
The enzyme lipase, digests fat cells with the production of fatty acids.
fatty acids +with calcium calcium soaps,/dull opaque white patches.
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29. TYPES OF NECROSIS 4. Fat Necrosis: 2. Traumatic fat necrosis:
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TYPES OF NECROSIS
4. Fat Necrosis:
2. Traumatic fat necrosis:
It occurs due to trauma of the adipose tissue of breast and subcutaneous fat.
The fat cells rupture and self-digestion takes place with release of fatty acids, which combine with calcium.
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30. dystrophic calcification
Inflammation
surrounds necrotic
area
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Drainage
of liquefied
tissue by
lymphatics
Phagocytosis
necrotic tissue
Necrosis
Large areas
fibrous capsule
dystrophic calcification
Small areas
Regeneration/ fibrosis

31. Apoptosis Necrosis involves few or single cells.
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Apoptosis
involves few or single cells.
Occur without injury or mild injury not causing necrosis
energy-dependent programmed cell death Removal of unnecessary or diseased cells
Not associated with release of chemical mediators,
it does not excite inflammation.
It is not accompanied by healing or calcification.
Formation of apoptic bodies,
Necrosis
death of cells within the living body caused by an irritant.
occurs directly or follows reversible injury
associated with release of chemical mediators
Inflammation surrounds the necrotic area.
accompanied by healing & calcification.
accompanied by nucleus Karyolysis

32. APOPTOSIS Morphological changes: Cell shrinkage
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APOPTOSIS
Morphological changes:
Cell shrinkage
Chromatin condensation followed by fragmentation of DNA.
Formation of apoptic bodies, composed of cytoplasm with/without nuclear fragments.
Phagocytosis of apoptic cells or bodies by macrophages.

33. APOPTOSIS In physiological conditions :
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APOPTOSIS
In physiological conditions :
Hormone dependent / regression of lactating breast after stopping lactation.
Normal turnover of cells.
Programmed cell destruction during embryonic development.
In pathological conditions :
Reduction of cell number in atrophy.
In cases of mild radiation injury.
Cell death in tumour regression
Liver cells in viral hepatitis.
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34. INTRACELLULAR ACCUMULATIONS
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INTRACELLULAR ACCUMULATIONS
The following substances may accumulate inside the cells:
water as in cloudy and hydropic swelling,
fat as in fatty change,
mucin as in mucoid change,
glycogen as in glycogen storage disease
protein as in hyaline change and
pigments.
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35. Types of degeneration:
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Types of degeneration:
4. Mucoid change: (Mucoid Degeneration)
Accumulation of mucin inside the epithelial cells, which swell
Cells rupture release of mucin (catarrhal inflammation).
Extracellular accumulation of mucin is called MYXOMATOUS DEGENERATION.
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36. Types of degeneration:
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Types of degeneration:
Hyaline change: (Hyalinosis)
The cellular or extracellular deposition of “hyaline” (protein material) gives a homogenous, structureless, glassy pink appearance.
Connective tissue (extracellular) hyalinosis is commonly seen in old scars, blood vessels
Cellular hyalinosis : in the islets of Langerhan’s in diabetes mellitus.
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37. Types of degeneration:
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Types of degeneration:
Waxy degeneration: (Zenker’s degeneration)
It is a special type of hyalinosis of the skeletal muscles.
The muscles loose its
striation and become
waxy, homogenous
and structureless
Causes: The bacterial
toxins and the excess
lactic acid accumulation
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38. Pigments Melanin: Melanin normally exists in skin, hair, eyes.
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Pigments
Melanin: Melanin normally exists in skin, hair, eyes.
increased melanin pigmentation (Hyperpigmentation):
Prolonged exposure to sun
Chloasma: Hyperpigmented brown patches affecting the face of women
during pregnancy,
the use of oral contraceptives.
Pigmented skin tumours: Benign and malignant melanomas.
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39. Pigments Haemoglobin- derived pigments: bilirubin and haemosiderin.
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Pigments
Haemoglobin- derived pigments: bilirubin and haemosiderin.
Bilirubin: is an iron-free pigment, which increases in liver in case of jaundice.
Haemosiderin: is brownish iron containing pigment.
Localized haemosiderosis: In areas of haemorrhage, in cases of lung congestion, around infarcts
Generalized haemosiderosis: excess iron in blood.
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40. Normal liver/- Bilirubin in liver
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Normal liver/- Bilirubin in liver
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41. - Hemosiderin in pulmonary macrophage
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- Hemosiderin in pulmonary macrophage
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42. EXTRACELLULAR DEPOSITIONS
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EXTRACELLULAR DEPOSITIONS
These include amyloid, cholesterol, uric acid, calcium.
Amyloid:
Amyloidosis is the extracellular deposition of amyloid, an abnormal protein usually resulting from antigen-antibody reaction.
Amyloid deposits in the
walls of blood vessels and
basement membranes.
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43. Amyloid proteins are of two types:
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Amyloid proteins are of two types:
Immunoglobulins secreted by plasma cells.
Amyloid associated protein present as a
Precursor protein in serum.
Markedly increased in chronic inflammatory and destructive diseases, as in tuberculosis.
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44. 4/22/2017

45. 4/22/2017

46. Cholesterol The normal cholesterol level in blood is 150-250 mg/100
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Cholesterol
The normal cholesterol level in blood is mg/100
Hypercholesterolemia may be:
Physiological as in pregnancy and lactation.
Pathological hypercholesterolemia results in the deposition of cholesterol in the intima of the arteries (atherosclerosis) or in skin (xanthoma).
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47. 4/22/2017
Xanthomas
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48. 4/22/2017
Uric acid
Normal end product of the metabolism of the nucleic acid purine.
Causes:
Primary gout with known or unknown enzyme defect, it may be hereditary or
secondary gout due to increase nucleoprotein breakdown, as in chronic leukemias.
increase of serum uric acid to above 6 mg% (normal= 3-6mg %), known as hyperuricemia
the deposition of sodium urate crystals in tissues, known as gout.
The deposit forms small masses called tophi.
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49. Tophus on the elbow of a middle aged man with chronic gout.
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Tophus on the elbow of a middle aged man with chronic gout.
gouty tophi of the helix of the ear.
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50. 4/22/2017
Uric acid
The urate crystals deposit in joints (particularly the big toe, ankle),
cartilage of the eye, ear and nose,
in cardiac valves and in
the interstitial tissue of kidney leading to urate stones in the kidney and renal failure
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51. 4/22/2017
Calcium
Pathological calcification is the deposition of calcium salts (phosphate and carbonate) in sites other than bone and teeth.
The calcified tissue appears chalky white and hard.
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52. Types of pathological calcification
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Types of pathological calcification
Dystrophic calcification:
Calcification of injured or necrotic tissues despite the normal serum calcium level.
It occurs in:
degenerated tissues as old scars, degenerated heart valves
necrotic tissues as old thrombi, old infarcts, fat necrosis, liquefactive necrosis, caseous tuberculous lesions and dead parasites and ova of bilharziasis
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53. Types of pathological calcification
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Types of pathological calcification
Dystrophic calcification:
The cause of calcium deposition and the formation of calcium phosphate crystals is
breakdown of organic phosphate leading to local alkalinity in the necrotic tissue,
increased phosphatase activity or
release of phosphate from nucleoprotein breakdown.
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54. Metastatic calcification:
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Metastatic calcification:
This is the calcification of normal living tissues due to hypercalcaemia.
Causes: of hypercalcaemia include
Increased calcium mobilization from bone
Bone destruction by malignant tumours and
Prolonged immobilization.
Hyperparathyroid
Increased calcium absorption from intestine as in hypervitaminosis D and excess milk intake
Chronic renal disease
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55. Metastatic calcification:
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Metastatic calcification:
Acid secretions or rapid changes in pH contribute to calcium salt formation
It occurs in
1. Mucosa of stomach.
2. Renal tubules.
3. Walls of the lung alveoli.
NB Hypercalcaemia accentuate dystrophic calcification
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56. Metastastic calcification in the lung, with hypercalcaemia
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Metastastic calcification in the lung, with hypercalcaemia
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57. Types of pathological calcification
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Types of pathological calcification
Idiopathic calcinosis:
This is calcification of unknown cause that may affect skin and other soft tissues, despite normal tissue and calcium level.
Stones:
Urinary stone, biliary stones and salivary duct stones.
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58. Types of pathological calcification
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Types of pathological calcification
The decrease in calcium level in bones:
In children leads to rickets, mainly due to vitamin D deficiency
In women leads to low bone density (Osteomalacia) at the menopause due to hormonal imbalance.
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59. 4/22/2017
GROWTH DISTURBANCES
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60. Disorders of Growth: Decreased growth Increased growth
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Disorders of Growth:
Decreased growth
Atrophy, Hypoplasia, Aplasia
Increased growth
Non Neoplastic – Normal DNA
Due to a need.. Controlled.
Neoplastic – Abnormal DNA
not needed, auto, uncontrolled.
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61. 4/22/2017
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62. 4/22/2017
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63. 4/22/2017
ATROPHY
Atrophy is the decrease in size and weight of a tissue or organ after it has reached its full development.
Atrophy may be due to reduction in number or size of component cells, or both.
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64. Types of atrophy: A- Physiological atrophy:
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Types of atrophy:
A- Physiological atrophy:
Some embryonic structures undergo atrophy during fetal development.
Atrophy of uterus, ovaries and breast after menopause due to diminished hormone stimulation.
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65. 4/22/2017
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66. Muscle ischemic atrophy:
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Muscle ischemic atrophy:
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67. Kidneys, normal (left) and ischemic atrophy (right)
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Kidneys, normal (left) and ischemic atrophy (right)
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68. 4/22/2017
HYPERTROPHY
Hypertrophy is the increase in size and weight of a tissue or organ due to increase in the size of cells, to meet increased functional demand.
Types of hypertrophy:
A- Physiological hypertrophy
Pregnant uterus due to hormone stimulation.
Hypertrophy of striated muscles in muscle builders.
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69. 4/22/2017
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70. 4/22/2017
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71. LVH in Chronic Hypertension:
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LVH in Chronic Hypertension:
Left Ventricular Hypertrophy

72. Thyroid gland, normal / hypertrophy and hyperplasia
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Thyroid gland, normal / hypertrophy and hyperplasia
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73. 4/22/2017
HYPERPLASIA
Hyperplasia is the increase in size and weight of a tissue or organ due to increase in the number of cells.
Hyperplasia can occur only in cells capable of division i.e. all cells except nerve cells, skeletal and cardiac muscle cells.
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74. Types of hyperplasia: A- Physiological hyperplasia:
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Types of hyperplasia:
A- Physiological hyperplasia:
Occurs in the breast and genital organs at puberty.
B- Pathological hyperplasia:
1. Hormonal hyperplasia: e.g. endometrial and mammary hyperplasia due to excessive oestrogen stimulation.
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75. B- Pathological hyperplasia:
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B- Pathological hyperplasia:
2. Compensatory hyperplasia (may be considered physiological or pathological):
Bone marrow hyperplasia following haemorrhage or haemolysis and in some anemia.
Hyperplasia of the liver after partial hepatectomy, restoring the normal liver weight within two weeks.
3. Irritation hyperplasia of lymphoid tissue in response to antigenic stimulation.
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76. Sequels of Necrosis: Cell Death Necrosis Autolysis Phagocytosis
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Sequels of Necrosis:
Cell Death
Necrosis
Autolysis
Phagocytosis
Organization & fibrous repair.
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77. APOPTOSIS Apoptosis/ cell death /involves few or single cells.
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APOPTOSIS
Apoptosis/ cell death /involves few or single cells.
It is an energy-dependent programmed cell death
Removal of unnecessary or diseased cells.
Occur without tissue injury or with mild injury not causing necrosis.
Not associated with release of chemical mediators, thus it does not excite inflammation.
It is not accompanied by healing or calcification.
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78. Heart hypertrophy in hypertension:
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Heart hypertrophy in hypertension:
Left Ventricle
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79. Muscle ischemic atrophy:
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Muscle ischemic atrophy:
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80. Types of Amyloidosis: Localized Amyloidosis:
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Types of Amyloidosis:
Localized Amyloidosis:
a. Senile Amyloidosis of brain: as in case of Alzheimer disease,
b. Tumours of endocrine gland: thyroid, pancreas.
c. Localized idiopathic: Larynx, tongue, heart, urinary bladder, muscles…etc
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81. Infarction - Adrenal gland:
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Infarction - Adrenal gland:
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82. 4/22/2017
GROWTH DISTURBANCES
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83. Disorders of Growth: Decreased growth Increased growth
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Disorders of Growth:
Decreased growth
Atrophy, Hypoplasia, Aplasia
Increased growth
Non Neoplastic – Normal DNA
Due to a need.. Controlled.
Neoplastic – Abnormal DNA
not needed, auto, uncontrolled.
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85. 4/22/2017
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86. 4/22/2017
ATROPHY
Atrophy is the decrease in size and weight of a tissue or organ after it has reached its full development.
Atrophy may be due to reduction in number or size of component cells, or both.
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87. Types of atrophy: A- Physiological atrophy:
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Types of atrophy:
A- Physiological atrophy:
Some embryonic structures undergo atrophy during fetal development.
Atrophy of uterus, ovaries and breast after menopause due to diminished hormone stimulation.
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88. 4/22/2017

89. Muscle ischemic atrophy:
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Muscle ischemic atrophy:
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90. Kidneys, normal (left) and ischemic atrophy (right)
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Kidneys, normal (left) and ischemic atrophy (right)
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91. 4/22/2017
HYPERTROPHY
Hypertrophy is the increase in size and weight of a tissue or organ due to increase in the size of cells, to meet increased functional demand.
Types of hypertrophy:
A- Physiological hypertrophy
Pregnant uterus due to hormone stimulation.
Hypertrophy of striated muscles in muscle builders.
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92. 4/22/2017
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93. Renal Infarction - Coagulative
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Renal Infarction - Coagulative
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94. Splenic Infarction - Coagulative necrosis
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Splenic Infarction - Coagulative necrosis
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