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Pathomorphology Lecture 1

Definition: study and diagnosis of disease;synonymous of disease

History:
- 20BC-Ancient Egypt; ‘Smith papyrus’->Imhotep describes cancer
- Babylon/Ancient Italy-liver appears as lobular structure in
statues
- Ancient Greece-heart, aorta, nerves described.
- 13th-17th century-anatomical theatres
- Andrea Vesalius-‘De humana corpis fabrica’ - morbid anatomy
- 1562(Fernell)-first pathology->autopsy as method to describe
cause of death.Introduced pathology and physiology as terms.
- 1761(Morgagni)- microscope
- New Era- Schleiden and Schwann-microscope and Schwann cells
in nose
- Rudolf Virchow’s era- inflammation- ‘Die Zellularpathologie’ . In
1858 defines all cells as basic structure, relates the structure of
organs with functions and defines disease as life at altered
conditions.
- Today:
4 components of disease: cause(etiology), mechanism of
development(pathogenesis), structural alterations of
cells(morphologic change), consequences of changes(clinical
manifestations/signs).
Further separated into divisions based on either system studied
(eg. dermatopathology) or focus of examination (eg. forensic).

Subdivisions:

1. General Pathology: general appearance of pathological

alterations- cell injuries, necrosis, apoptosis, abnormal deposits,
blood and water flow alterations, inflammation, immune-
mediated disease, tumours, monstrosities.
2. Clinical Pathology: after death

Basic Terms:

- health: steady state/condition, homeostasis

- disease: imbalance
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- death: clinical and biological
- etiology: cause of disease
- pathogenesis: mechanism of moribound processes
- sanogenesis: process of healing

Basic Methods used:

- autopsy/necropsy
- biopsy -needle/surgical
- histology/histochemistry
- cytology
- immunochemistry
- electron microscopy
- quantitative methods

Cellular Injuries:

Structural alterations: minimal or expressed, reversible/irreversible

Causes: ischaemia, physical, chemical, biological factors, altered
metabolic processes, genetically-defined malformations, immune
reactions.

Ischaemic Hypoxic Cell Injury:

One of the most common.Hypoxia-> blocks aerobic

respiration.Ischaemia(loss of blood);high nutrients, high
metabolites->impairs aerobic glycolysis as well.

Reversible Ischaemic Injury:

Destructed blood vessels->In mitochondrion; decreased oxidative

phosphorylation,decreased ATP, decreased activity of Na/K pump.
Anaerobic glycolysis(starting molecule->phosphofructokinase)->
influx of Na and K in cell(water also flows in) and thus the form of
the cell is altered.
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Outcome-> swelling of the cell and loss of microvilli;swelling of
external membrane and mitochondrion. Formation of bleps and
myelin-chromatin clumping, detachment of ribosome, low protein
synthesis.
If the injury stops the recovery begins.
Examples:
- heart muscle stops for 60 seconds, coronary
occlusion,myocardial cell reversibly damaged so it can be fixed
with surgery.
- renal tubule epithelial cells;after death destruction, no microvilli,
bleps, swelling or clumping.

Irreversible Ischaemic Injury:

If ischaemia persists;apoptosis, necrosis. The situation has

reached the ‘point of no return’ -> impairment of mitochondrial
disfunction, alteration of plasma membrane.Morphologic/functional
changes:extensive damage to organelle membrane, loss of protein,
coenzyme and RNA, Ca influx.
Swelling/leaking of lysosomes: leakage of acid hydrolases into
cytoplasm- low pH.Paler cytoplasm of irreversibly damaged cell.
After cell death:
- cellular compartments digested by lysosomes.
- leakage of cellular enzymes into ECM(liver ALT, muscle CK)
- influx of macromolecules from ECM
- cell debris-> fatty-acid residue or removed by phagocytosis.

Mechanism of Chemical Injury:

Direct interaction-> some chemicals act by damaging particular

organelles (cyanide,HCL). Conversion to reactive toxic metabolites-
cytochrome P450 in SER of liver.Toxic metabolites(free
radicals),Liver particularly suseptible to toxic injury by P450.

- Acetaminophen toxicity(temperature lowering drug) headache.6

tablets- liver-blocked-death.Toxic metabolite is cause of
hepatocyte death.Cats and dogs produce more paraminophenol.
- Carbon tetrachloride/chloroform. Impairement of apoprotein
synthesis in liver.Triglyceride removal-if not liver removal
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Morphology of Cell Injury: visible changes;necrosis.Cell swelling-
reversible when stimulus removed.Cell death is irreversible.
20-60mins of coronary artery occlusion.
Biochemical change, release enzyme and EM change within 2hrs.

Reversible Cell Injury (cell degeneration):

1.Cellular Swelling
2.Fatty Change

Irreversible Cell Injury:

1.Necrosis:
a) etiology - early
b) swelling, enlarged, wet.
c) histology - cells enlarged, pale cytoplasm, cloudy appearance
‘swelling’. ‘hydropic degeneration’,ballooning degeneration(in
epidermis and other tissues excluding CNS.
d)ultrastructural appearance
e)prognosis
2.Apoptosis:
a)etiology - hypoxic, toxic, metabolic.
b)abnormal accumulation of fats in cell
c) metabolic cells of fatty acids-liver, renal tubular epithelium,
myocardium.
d) metabolic abnormalities
e) may proceed or accompany cell swelling