Introducti on to

Patholo gy
Ma. Minda Luz M. Manuguid, M.D.

definition of Terms
•Pathology – pathos – suffering; disease
logos – study; knowledge - branch of medicine concerned with determining the nature & course of diseases by analyzing body tissues & fluids - study of diseases

• General vs. Systemic/Special:  General Pathology – disease mechanisms – may be common to several diseases  Systemic/Special Pathology – genetic, cellular, molecular manifestations of specific diseases • Anatomic/Surgical vs. Clinical  Anatomic/Surgical Pathology – Autopsy; Biopsy; Cytopathology  Clinical Pathology – Hematology & Blood Banking; Clinical Chemistry; Clinical Microscopy; Serology; Microbiology

Forensic Pathology – medicolegal investigations Cardiovascular Pathology

• Autopsy/Necropsy – medical

examination of a dead human body, to determine cause of death, diagnosis, or disease progression • Biopsy – bio - ‘life’ ; opsis - ‘a viewing’ – the removal of a sample of tissue from a living person for laboratory examination; primarily for the detection of Cancer
Excision biopsy Incision biopsy Fine needle aspiration biopsy (FNAB) Frozen section biopsy

•Exfoliative Cytopathology – microscopic

examination of cells in body tissues or body fluids primarily to determine if they are cancerous; uses the Papanicolaou method of staining, hence the term ‘Pap’ smear

•Clinical Microscopy •Hematology & Blood Banking •Serology & Immunology •Microbiology/Bacteriology •Clinical Chemistry

Four Aspects of a Disease
Etiology – cause /causes of the disease Pathogenesis – development of the disease; chronologic progression of pathologic changes Morphologic changes - “ signs ” – anatomic / histologic changes; objective; can be seen or measured Functional derangements/Clinical significance “symptoms” – subjective; what a patient feels; limitations on patients’ normal activities; prognosis

Cellular Pathology: Cellular Adaptation Cellular Injury & Cell Death

Ma. Minda Luz M. Manuguid, M.D.

Cellular Adaptation; Cellular Injury; Cell Death Normal Cell
Cellular--------------------Reversible---------------Cell Death Adaptation Injury Atrophy ‫٭‬Necrosis  Hypertrophy ‫٭‬Apoptosis  Hyperplasia  Metaplasia

♦ Fatty Change ♦Cloudy swelling

The Cell Cycle
 Labile cells – cells that never  
leave the cell cycle; retain their mitotic ability Permanent cells – cells that leave the cell cycle permanently; no mitotic ability Stable cells – cells that have temporarily left the cell cycle; mitotic ability is retained but quiescent, may occur when needed

G2

M= MITOSIS

G1

Cellular Adaptation
Hyperplasia – increase in number of cells
through cell division

Hypertrophy – increase in cell size due to
increase in cellular components

Atrophy – decrease in cell size due to

reduction in cell components; associated with increased autophagic vacuoles & lipofuscin pigment to another due to chronic irritation; always pathologic

Metaplasia – change from one adult cell type

Cellular Adaptation
(cystic) hyperplasia atrophy

(squamous) metaplasia hypertrophy

Cellular Injury: General Considerations
 The structural & biochemical elements of the cell are so closely inter-related that whatever the precise point of initial attack, injury at one locus leads to wide-ranging secondary effects  Morphologic changes become apparent only when some critical biochemical system has been deranged  Reactions of the cell to injurious stimuli depend on the type, duration, & severity of injury, as well as on the type, state, & adaptability of the cell

Causes of Cellular Injury
HYPOXIA  PHYSICAL AGENTS  CHEMICAL AGENTS/DRUGS  BIOLOGIC AGENTS  IMMUNOLOGIC REACTIONS  GENETIC DERANGEMENTS  NUTRITIONAL IMBALANCES

Cellular Components/Processes most vulnerable to  Cell membrane – Selective permeability Injury
 Mitochondria – Aerobic respiration / Oxidative
phosphorylation – Protein synthesis

 Ribosomes / Rough Endoplasmic reticulum  Nuclear chromatin – Genetic material / DNA –
control of cellular activities

Common Biochemical themes in Cellular Injury
ATP depletion & defects in Membrane permeability ↑ intracellular Calcium & loss of Calcium homeostasis ↓ Oxygen & production of Oxygen-derived free radicals

Free Radicals

  

definition – chemical species that have a single unpaired electron in an outer orbital; extremely reactive & unstable, can react with organic or inorganic chemicals, esp. cell membranes & nucleic acids Hydroxyl OH¯; Hydrogen peroxide H2O2; Superoxide O2¯; Nitric oxide NO actions – lipid peroxidation of cell membranes; denaturation of proteins; DNA mutation neutralized by Anti-oxidants (vit E, vit C, sulfhydril-containing compounds Cysteine, Glutathione-GSH, Albumin, Ceruloplasmin, Transferrin, Superoxide dismutase, GSH peroxidase)

Reversible Cellular Injury
Fatty change –
replacement of parenchymal cells by lipid droplets- most commonly seen in the liver accumulation of water within cells - most commonly seen in renal tubular cells: “ground glass” or “cloudy” histologic appearance

Cloudy swelling –

Irreversible Cellular Injury / Cell Death
NECROSIS – changes
that occur in the irreversibly injured cell denaturation of proteins & subsequent enzymatic digestion; always pathologic; involves a group of cells; accompanied by inflammation

APOPTOSIS –

“falling off”chromatin condensation & subsequent fragmentation of the dead cell into “apoptotic bodies”; physiologic or pathologic; may occur in a single cell; no inflammation

Patterns of Necrosis
Coagulative/Coagulation Coagulative/Coagulation – cell shape is
preserved; denaturation of cellular proteins; “tombstone cells” Liquefactive/Liquefaction Liquefactive/Liquefaction – amorphous necrotic debris due to hydrolytic enzymatic dissolution; typical of brain injury; abscess Caseous/ Caseous/ Caseation – coagulation, then incomplete dissolution; typical of TB Gangrenous/Gangrene Gangrenous/Gangrene – coagulation + bacterial contamination (varying degrees of liquefaction): wet or dry - diabetic wounds Fat Fat Necrosis : Traumatic – breast; subcutaneous fat; Enzymatic – pancreatitis

Coagulative Necrosis /Liquefactive Necrosis

Caseation Necrosis

Gangrenous Necrosis

Traumatic & Enzymatic Fat Necrosis

Apoptosis
 Physiologic :

programmed destruction of cells during embryogenesis & organogenesis; “developmental involution”; “programmed cell death” in adults, hormone-dependent involution e.g. menopause, post-partum, thymic involution cell deletion in proliferating cell populations e.g. epithelial renewal cell death in tumors; cell death in viral injury death of immune cells; cytotoxic T-cell action pathologic atrophy of hormone-dependent tissues in parenchymal organs due to duct obstruction

 Pathologic :
   

Apoptosis

Councilman bodies in Hepatitis

Pathologic Calcification :

deposition of Calcium salts + smaller amounts of Fe, Mg, & other mineral salts  Dystrophic – in dead  Metastatic – in vital or viable tissues when there is or dying tissues, hypercalcemia, almost always regardless of Ca with some derangement of Ca metabolism levels, in the usually in interstitial tissues of absence of blood vessels, kidneys, lungs, gastric mucosa abnormal Ca hyperCa: hyperparathyroidism metabolism hyperthyroidism, systemic
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atheromas aging/damaged heart valves myocardial infarcts tuberculomas psammoma bodies

sarcoidosis, vit D intoxication Addison’s dse, metastatic tumors, bone tumors, MM

Pathologic Calcification
 gross: fine white granules or clumps felt as gritty deposits; “crumbled chalk” appearance  microscopic: H & E : basophilic amorphous granular or clumped deposits, intra- or extra- cellular; psammoma bodies – lamellated circular Ca deposits – seen in papillary tumors

Pathologic Calcification
Dystrophic calcification –
deposition of Calcium in dead or dying tissues

Metastatic calcification –

deposition of Calcium in viable tissues - due to hypercalcemia

Intracellular Accumulations
 intranuclear or cytoplasmic  normal cellular constituent or abnormal substance  endogenous or exogenous abnormal substance  may be a pigment (endogenous or exogenous)  may be an infectious product  accumulation may be due to overproduction, inadequate metabolism & excretion, or both

Intracellular Accumulations
 Lipids – accumulation of Triglycerides within parenchymal cells
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Fatty Liver of Alcoholism, Kwashiorkor, DM, Obesity, Anoxia & Toxins may also occur in the Heart, Muscles, Kidneys

 Proteins – usually as rounded eosinophilic droplets, vacuoles, masses
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Hyaline droplets in kidneys(PCT) in dses with proteinuria Russell bodies – excess Igs in plasma cells Glycogen storage disorders

 Carbohydrates

 Pigments

Lipofuscin, Hematin, Melanin, homogentisic acid,

Miscellany
 Lysosomes
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Heterophagy – ingestion of outside material by endocytosis Autophagy – intracellular material (e.g. senescent organelles) is sequestered into autophagic vacuoles Residual bodies – lysosomes with undigested debris Lipofuscin – yellow-brown pigment granules that represent undigested material from intracellular lipid peroxidation Barbiturates, Steroids, Carcinogenic hydrocarbons, insecticides, Alcohol, CCl4

 Smooth ER induction (Hypertrophy) – for detoxification fn
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Miscellany
 Mitochondria : alterations in size, shape, number
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Megamitochondria – very large due to increased metabolic demands e.g. in alcoholic hepatitis, nutritional deficiencies Mitochondrial myopathies - in number, + abnormal cristae & crystalloids seen in skeletal muscle disorders increase in size & number – in Oncocytomas of the salivary glands, thyroids, parathyroids, kidneys defects in cell locomotion & intracellular organelle movements e.g. Chediak-Hegashi syndrome; immotile cilia syndrome accumulation of microtubules & intermediate filaments e.g. neurofibrillary tangles in Alzheimer’s disease

 Cytoskeleton:
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Thank you & Good Day !