Introductio

n
to
Patholog
y
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 ♦ Fatty Change ‫٭‬Necrosis

 Hypertrophy ♦Cloudy swelling ‫٭‬Apoptosis
 Hyperplasia
 Metaplasia
 The Cell Cycle
 Labile cells – cells that
never leave the cell cycle;
retain their mitotic ability
 Permanent cells – cells
G2 M= MITOSIS
that leave the cell cycle
permanently; no mitotic ability
 Stable cells – cells that
have temporarily left the cell G1

cycle; mitotic ability is retained

but quiescent, may occur when
needed
 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
Metaplasia – change from one adult cell type to
another due to chronic irritation; always pathologic
 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
Injury
 Cell membrane – Selective permeability
 Mitochondria – Aerobic respiration /
Oxidative phosphorylation
 Ribosomes / Rough Endoplasmic
reticulum – Protein synthesis
 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
Cloudy swelling –
accumulation of water within
cells - most commonly seen in
renal tubular cells: “ground
glass” or “cloudy” histologic
appearance
Irreversible Cellular Injury / Cell
Death
NECROSIS – APOPTOSIS –
changes that occur in “falling off”- chromatin
the irreversibly injured condensation &
subsequent
cell - denaturation of
fragmentation of the
proteins & subsequent dead cell into
enzymatic digestion; “apoptotic bodies”;
always pathologic; physiologic or
involves a group of pathologic; may occur
cells; accompanied by in a single cell; no
inflammation inflammation
 Patterns of Necrosis
Coagulative/Coagulation – cell shape is
preserved; denaturation of cellular proteins; “tombstone
cells”
Liquefactive/Liquefaction – amorphous necrotic
debris due to hydrolytic enzymatic dissolution; typical of
brain injury; abscess
Caseous/ Caseation – coagulation, then incomplete
dissolution; typical of TB
Gangrenous/Gangrene – coagulation + bacterial
contamination (varying degrees of liquefaction):
wet or dry - diabetic wounds
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
 Pathologic :
 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
Apoptosis

Councilman bodies in Hepatitis

Pathologic Calcification : deposition of
Calcium salts + smaller amounts of Fe, Mg, & other
mineral salts
 Dystrophic – in dead or  Metastatic – in vital or
dying tissues, regardless viable tissues when there is
of Ca levels, in the hypercalcemia, almost
absence of abnormal Ca always with some
metabolism derangement of Ca
 atheromas metabolism
 aging/damaged heart  usually in interstitial tissues of
valves blood vessels, kidneys, lungs,
gastric mucosa
 myocardial infarcts
 hyperCa: hyperparathyroidism
 tuberculomas hyperthyroidism, systemic
 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
 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
 Hyaline droplets in kidneys(PCT) in dses with proteinuria
 Russell bodies – excess Igs in plasma cells
 Carbohydrates
 Glycogen storage disorders
 Pigments
 Lipofuscin, Hematin, Melanin, homogentisic acid,
 Miscellany
 Lysosomes
 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
 Smooth ER induction (Hypertrophy) – for detoxification
fn
 Barbiturates, Steroids,
 Carcinogenic hydrocarbons, insecticides, Alcohol, CCl4
 Miscellany
 Mitochondria : alterations in size, shape, number
 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
 Cytoskeleton:
 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
 Thank
you &

Good Day
!