4/22/2017 Clinical Pathology 4/22/2017

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. 4/22/2017

Course Contents Introduction and definitions, 4/22/2017 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 4/22/2017

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 4/22/2017

Weighting of Assessments 4/22/2017 Weighting of Assessments Mid-Term Examination 10 % (10 Marks) Final-term Examination 50% (50 Marks) Oral Examination. 15% (15 Marks) Practical Examination 25% (25 Marks) Semester Work Other types of assessment Total 100% (100 Marks) 4/22/2017

Recommended Books Recommended Books 4/22/2017 Recommended Books Recommended Books Pathologic Basis of Disease, Robbins and Cortran, Elsevier Saunders 8th Edition, 2010 4/22/2017

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. 4/22/2017

4/22/2017 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. 4/22/2017

4/22/2017 Cellular Injury 4/22/2017

Response to Injury: Adaptations (reversible) 4/22/2017 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 4/22/2017

REVERSIBLE CELL INJURY (DEGENERATION) 4/22/2017 REVERSIBLE CELL INJURY (DEGENERATION) Functional and morphological changes that are reversible 4/22/2017

REVERSIBLE CELL INJURY (DEGENERATION) 4/22/2017 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. 4/22/2017 1:00 AM

Types of degeneration: 4/22/2017 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. 4/22/2017 1:00 AM

Normal liver/ Cloudy swelling 4/22/2017 Normal liver/ Cloudy swelling 4/22/2017 1:00 AM

Types of degeneration: 4/22/2017 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. 4/22/2017 1:00 AM

Hydropic change in ischemic - kidney 4/22/2017 Hydropic change in ischemic - kidney Microvilli 4/22/2017 1:00 AM

Types of degeneration: 4/22/2017 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 4/22/2017 1:00 AM

Fatty change (steatosis) 4/22/2017 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. 4/22/2017 1:00 AM

Normal liver/ fatty change (Steatosis) 4/22/2017 Normal liver/ fatty change (Steatosis) 4/22/2017 1:00 AM

IRREVERSIBLE CELL INJURY (NECROSIS) 4/22/2017 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 4/22/2017 1:00 AM

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IRREVERSIBLE CELL INJURY (NECROSIS) 4/22/2017 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 4/22/2017 1:00 AM

22 - Normal cardiac muscle/ coagulative necrosis 4/22/2017 22 - Normal cardiac muscle/ coagulative necrosis 4/22/2017 1:00 AM

Types of Necrosis: Coagulative Necrosis: 4/22/2017 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 4/22/2017 1:00 AM

Types of Necrosis: Liquefactive Necrosis: 4/22/2017 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 4/22/2017 1:00 AM

Typical for tuberculous lesions. TYPES OF NECROSIS 4/22/2017 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 4/22/2017 1:00 AM

4/22/2017 Caseous Necrosis 4/22/2017 1:00 AM

TYPES OF NECROSIS 4. Fat Necrosis: Enzymatic fat necrosis: 4/22/2017 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. 4/22/2017 1:00 AM

TYPES OF NECROSIS 4. Fat Necrosis: 2. Traumatic fat necrosis: 4/22/2017 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. 4/22/2017 1:00 AM

dystrophic calcification Inflammation surrounds necrotic area 4/22/2017 Drainage of liquefied tissue by lymphatics Phagocytosis necrotic tissue Necrosis Large areas fibrous capsule dystrophic calcification Small areas Regeneration/ fibrosis

Apoptosis Necrosis involves few or single cells. 4/22/2017 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

APOPTOSIS Morphological changes: Cell shrinkage 4/22/2017 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.

APOPTOSIS In physiological conditions : 4/22/2017 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. 4/22/2017 1:00 AM

INTRACELLULAR ACCUMULATIONS 4/22/2017 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. 4/22/2017

Types of degeneration: 4/22/2017 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. 4/22/2017

Types of degeneration: 4/22/2017 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. 4/22/2017

Types of degeneration: 4/22/2017 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 4/22/2017

Pigments Melanin: Melanin normally exists in skin, hair, eyes. 4/22/2017 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. 4/22/2017

Pigments Haemoglobin- derived pigments: bilirubin and haemosiderin. 4/22/2017 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. 4/22/2017

Normal liver/- Bilirubin in liver 4/22/2017 Normal liver/- Bilirubin in liver 4/22/2017

- Hemosiderin in pulmonary macrophage 4/22/2017 - Hemosiderin in pulmonary macrophage 4/22/2017

EXTRACELLULAR DEPOSITIONS 4/22/2017 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. 4/22/2017

Amyloid proteins are of two types: 4/22/2017 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. 4/22/2017

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Cholesterol The normal cholesterol level in blood is 150-250 mg/100 4/22/2017 Cholesterol The normal cholesterol level in blood is 150-250 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). 4/22/2017

4/22/2017 Xanthomas 4/22/2017

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. 4/22/2017

Tophus on the elbow of a middle aged man with chronic gout. 4/22/2017 Tophus on the elbow of a middle aged man with chronic gout. gouty tophi of the helix of the ear. 4/22/2017

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 4/22/2017

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. 4/22/2017

Types of pathological calcification 4/22/2017 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 4/22/2017

Types of pathological calcification 4/22/2017 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. 4/22/2017

Metastatic calcification: 4/22/2017 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 4/22/2017

Metastatic calcification: 4/22/2017 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 4/22/2017

Metastastic calcification in the lung, with hypercalcaemia 4/22/2017 Metastastic calcification in the lung, with hypercalcaemia 4/22/2017

Types of pathological calcification 4/22/2017 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. 4/22/2017

Types of pathological calcification 4/22/2017 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. 4/22/2017

4/22/2017 GROWTH DISTURBANCES 4/22/2017

Disorders of Growth: Decreased growth Increased growth 4/22/2017 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. 4/22/2017

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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. 4/22/2017

Types of atrophy: A- Physiological atrophy: 4/22/2017 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. 4/22/2017

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Muscle ischemic atrophy: 4/22/2017 Muscle ischemic atrophy: 4/22/2017

Kidneys, normal (left) and ischemic atrophy (right) 4/22/2017 Kidneys, normal (left) and ischemic atrophy (right) 4/22/2017

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. 4/22/2017

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LVH in Chronic Hypertension: 4/22/2017 LVH in Chronic Hypertension: Left Ventricular Hypertrophy

Thyroid gland, normal / hypertrophy and hyperplasia 4/22/2017 Thyroid gland, normal / hypertrophy and hyperplasia 4/22/2017

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. 4/22/2017

Types of hyperplasia: A- Physiological hyperplasia: 4/22/2017 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. 4/22/2017

B- Pathological hyperplasia: 4/22/2017 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. 4/22/2017

Sequels of Necrosis: Cell Death Necrosis Autolysis Phagocytosis 4/22/2017 Sequels of Necrosis: Cell Death Necrosis Autolysis Phagocytosis Organization & fibrous repair. 4/22/2017

APOPTOSIS Apoptosis/ cell death /involves few or single cells. 4/22/2017 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. 4/22/2017

Heart hypertrophy in hypertension: 4/22/2017 Heart hypertrophy in hypertension: Left Ventricle 4/22/2017

Muscle ischemic atrophy: 4/22/2017 Muscle ischemic atrophy: 4/22/2017

Types of Amyloidosis: Localized Amyloidosis: 4/22/2017 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 4/22/2017

Infarction - Adrenal gland: 4/22/2017 Infarction - Adrenal gland: 4/22/2017

4/22/2017 GROWTH DISTURBANCES 4/22/2017

Disorders of Growth: Decreased growth Increased growth 4/22/2017 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. 4/22/2017

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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. 4/22/2017

Types of atrophy: A- Physiological atrophy: 4/22/2017 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. 4/22/2017

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Muscle ischemic atrophy: 4/22/2017 Muscle ischemic atrophy: 4/22/2017

Kidneys, normal (left) and ischemic atrophy (right) 4/22/2017 Kidneys, normal (left) and ischemic atrophy (right) 4/22/2017

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. 4/22/2017

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Renal Infarction - Coagulative 4/22/2017 Renal Infarction - Coagulative 4/22/2017

Splenic Infarction - Coagulative necrosis 4/22/2017 Splenic Infarction - Coagulative necrosis 4/22/2017