Introduction to Basic Pathology; Cellular Reaction to Injuries` Dr. ROOPA Pathophysiology Premed 2

Basic Pathophysiology Basic Pathology Basic Microbiology Bacteriology Virology Mycology Immunology Basic Pharmacology

What is Pathology?

Pathology Branch of Medicine Studies the underlying causes of diseases “etiology” Mechanisms that result in the signs and symptoms of the patient “pathogenesis”

Pathology Bridge between basic science and clinical practice “study of suffering” Divisions: General Pathology Systemic Pathology

The Cell

How do cells react to environmental stress? Hypertrophy Hyperplasia Aplasia Hypoplasia Atrophy Metaplasia

Hypertrophy Increase in protein synthesis/ organelles Increase in size of cells Increase in organ/tissue size

Hypertrophy

Hyperplasia Increase in NUMBER of cells Increase in size of organ/tissue Similar end result as hypertrophy May occur with hypertrophy

Hyperplasia

Aplasia Failure of cell production Agenesis or absence of an organ:fetus Loss of precursor cells:adults

Aplasia

Hypoplasia Decrease in cell production

Atrophy Decrease in mass of preexisting cells Smaller tissue/organ Most common causes: disuse poor nutrition lack of oxygen lack of endocrine stimulation aging injury of the nerves

Atrophy

Metaplasia Replacement of one tissue by another tissue Several forms: Squamous metaplasia Cartilaginous metaplasia osseous metaplasia myeloid metaplasia

Metaplasia

DEFINITION- DYSPLASIA Dysplasia means disordered growth, most commonly seen in squamous epithelial cells following chronic injury.

What are the causes of injury/stress? Hypoxic cell injury Free radical injury Chemical cell injury

Hypoxic cell injury Complete lack of oxygen/ decreased oxygen Anoxia or hypoxia Causes: ischemia anemia carbon monoxide poisoning decrease tissue perfusion poorly-oxygenated blood

Hypoxic cell injury

Early stage Hypoxic cell injury Decrease in production of ATP Changes in cell membrane Cellular swelling endoplasmic reticulum mitochondria Ribosomes disaggregate Failure of protein synthesis Clumping of chromatin

Late stage Cell membrane damage myelin blebs cell blebs

Cell Death Irreversible damage to the cell membranes Calcium influx Mitochondria calcifies Release of cellular enzymes Most vulnerable cells: neurons

Free radicals: superoxide and hydroxyl radicals Seen in: normal metabolism oxygen toxicity ionizing radiation UV light drugs/chemicals ischemia

Mechanisms to detoxify free radicals Glutathione Catalase Superoxide dismutase Vitamin A, C, E Cysteine,glutathione, selenium, ceruloplasmin Spontaneous decay

Chemical Injury Carbon tetrachloride and liver damage

NECROSIS AND APOPTOSIS sum of the morphologic changes that follow cellular death in the tissue or organs. Mainly 2 processes cause the morphologic changes of necrosis; Denaturation of proteins Enzymatic digestion of organelles n other cytosolic components.

Autolysis – cell digestion due to hydralytic enzymes derived from dead cells. Heterolysis ; derived from invading inflammatory cells.

Types of necrosis Coagulative necrosis Liquefactive necrosis Caseous necrosis Gangrenous necrosis Fibrinoid necrosis Fat necrosis

Coagulative necrosis Interruption of the blood supply Commonest form of necrosis Poor collateral circulation heart kidney Characteristic nuclear changes pyknosis karyorrhexis karyolysis disappearance of a nuclei

NUCLEAR CHANGES Karyolysis- disintegration and dissolution of a cell nucleus when a cell dies Due to DNA se activity Basophilia of chromatin fade

NUCLEAR CHANGES Pyknosis – a degenerative state of the cell nucleus -Nuclear shrinkage - Increased basophilia Karyorrhexis – nuclear fragmentation within 1 or 2 days nucleus disappears.

Coagulative Necrosis

Liquefactive necrosis Is typically found in the brain or in an abscess. Tissue is softened through the action of enzymes released from brain or in the case of an abscess, PMN.

Liquefactive necrosis

Caseous necrosis Coagulative + liquefactive “cheese - like” Part of granulomatous inflammation Classic picture: Tuberculosis

Caseous necrosis

Gangrenous necrosis Interuption of the blood supply to the lower extremities or bowels Wet type: complicated by liquefactive necrosis Dry type: complicated by coagulative necrosis

Gangrenous necrosis

Fibrinoid necrosis Immune-mediated vascular damage Protein – like material in the blood vessel walls

Fat necrosis Traumatic fat necrosis – after injury Breast Enzymatic fat necrosis – after inflammation Pancreas

FAT NECROSIS

APOPTOSIS -”Programmed cell death” Occurs when a cell dies through the activation of an internal suicide program. This is mainly useful in eliminating the unwanted cells with minimal disruption of the surronunding tissue. Can be seen mainly in the elimination of unwanted cells during embryogenesis.

Necrosis versus apoptosis Gross irreversible cell injury Passive form of cell death Does not require genes, protein synthesis Marked inflammatory reaction Physiologic programmed cell removal Active form of cell death Requires genes, proteins, energy No inflammatory reaction

Genes affecting apoptosis Inhibits: bcl-2 Facilitates: bax p53

Morphological features in apoptosis Involves small clusters of cells only No inflammatory cells Cell membrane blebs Cytoplasmic shrinkage Chromatin condensation Phagocytosis of apoptotic bodies