Place and role of the pathology in the medicine.

Structure of pathology and methods of investigation

Dr. Attila Zalatnai

TREATMENTS

THE DOCTOR HIM (HER)SELF

Technical arsenal

Operative techniques

Pharmacology

DISEASES

Molecular diagnostics

Genetic diagnostics

Radiologic diagnostics

Laboratory diagnostics

Clinical picture

Abnormal regulations

Morphological alterations

THE HUMAN

BEING

Psychology

FunctionPhysiology, biochemistry, molecular

mechanisms

StructureMacroscopic anatomy, embryology,

histology, subcellular morphology,

molecular level

STRUCTURE OF THE MEDICINE

Clinical symptoms

DISEASE

Laboratory alterations

Pathological alterations

- macroscopic level

- light microscopic level

- ultrastructural level

- molecular level

Imaging methods

Without pathology there is no modern diagnostics!

Law: „all surgically removed tissue must be sent to pathology!”

routine: 8 % formalin

other studies: 0,9 % NaCl

never should be dry!

Except: tooth

normal placenta

nail

eye lens

PARTS OF THE PATHOLOGY

Autopsy:

- obligatory in Hungary

- autopsy report - saved forever

- clinician must be present

Histopathology:

- it determines the therapeutic strategy

(gold standard)

- resection, excision, core biopsy

- intraoperative frozen section

- histopathological report - must be archived

Cytology:

- exfoliatíve cytology (e.g. fluids)

- abrasive cytology (cervix, bronchus, stoamch)

- fine needle aspiration cytology (FNAB, FNAC, ABC)

Molecular pathology:

Autopsy

- controls the clinical diagnoses (quality control)

- provides epidemiological data

- characterization of newly discovereddiseases

- better understanding of the naturalhistory of malignant diseases

- recognition of the morphologicalalterations (medical teaching)

- exclusion of forensic cases

- defence against the malpractice charges

History

Ancient Egyipt (3000- 1000. B.C)

Balming

Medical school of Alexandria (3rd c. B.C.)

Herophilos, Erazistratos

Anatomical textbook

Galen (131 – 200.)

Autopsies on animals

Synthesis of medicine in 8 volumes

Bologna, 14th century

Executed bodies

Benivieni (Florence, 15th centruy) „De abditis morborum causis”(20 autopsies)

Morgagni (1762)

„De sedibus et causis morborum”

70 „anatomical medical letters”

Clinicopathological view

Matthew Baillie (London, 1793)

„Morbid anatomy”

2nd Vienna School

Karl, Rokitansky (1804 – 1878)

85 000 autopsies

(30 000 personally)

„Handbuch der pathologischen Anatomie” - landmark

Pathological Institutes

Strassbourg

Edinborgh

Paris

Vienna

Pest (1844)

Histopathology

Determines the treatment strategies!

abscess forming inflammation antibacterial treatment

tbc specific antituberculotic treatment

metastasis search for primary neoplasm

removal of the whole organ

decides the extent of operation

staging of the malignant tumors

primary malignant lymph node tumor

chemotherapy

- characterization of the effusions

- screening for preneoplastic conditions

- recognition of the nature of focal lesions

(breast, thyroid, liver, salivary gland, brain…)

Cytology

Methods in pathology

macroscopy routine HE staining special stanings polarization

immunfluorescence tissue culture immunohistochemistry FISH

enzyme histochemistry elektron microscopy PCR FACS

Adaptation tissue reactions

(atrophy, hypertrophy, hyperplasia,

metaplasia)

Dr. Attila Zalatnai

Normal tissue

Abnormal noxas

degeneration adaptation

hyperplasia

hypertrophy

hyperplasia + hypertrophy

necrosis

death

superinfection

tissue loss

mutilation

resorption

cavitation

fistule

pseudocyst

Reparation

fibrosis

scarring

calcification

ossification

metaplasia

inflamm. atrophy

pseudometaplasia

pseudo-hypertrophy

regeneration

dysplasia

malignant transformation

((

Normal tissue

Abnormal noxas

degeneration adaptation

hyperplasia

hypertrophy

hyperplasia + hypertrophy

necrosis

death

superinfection

tissue loss

mutilation

resorption

cavitation

fistule

pseudocyst

Reparation

fibrosis

scarring

calcification

ossification

metaplasia

inflamm. atrophy

pseudometaplasia

pseudo-hypertrophy

regeneration

dysplasia

malignant transformation

((

Degenerations (dystrophies)

Results of metabolic cellular damage, morphological apprearances of the intracellulardisturbances

Many different causes – nonspecific!

- tissue hypoxia, shift in pH

- intracellular ionic imbalance

- toxic damage ártalmak

- distant effect of severe generalized inflammations

- burn, freezing

- intoxications

Parenchymatous degeneration (cloudy swelling)

Hydropic degeneration

Vacuolic degeneration

Fatty degeneration

Parenchymatous degeneration (cloudy swelling)

Impaired intracellular oxidation

Inefficient K/Na-pump

Increased membrane permeability

Increased intracellular water content

Parenchymatous organs (heart, liver, kidney)

Swollen, wet, pale brown, friable

Granular cytoplams

(swollen organelles)

Kidney: dilated stellate veins

Tubular lumens: virtual, narrow

Cytotoxic brain edema

Cerebellar herniation

CAUSES:

- blunt trauma

- ischemia, hypoxia

- diabetic ketoacidosis

- hepatic insufficiency

Hydropic and vacuolic degeneration

More severe cellular damage

Cytoplasmic water accumulation

Hypertonic solutions

Intoxications (coolant; etyleneglycol)

Hypokalemic conditions

(e.g. Conn-syndrome)

Fatty degeneration

Accumulation of neutral lipids (triglicerides) in the cytoplasm

Depending on the size of lipid droplets: microvesicular – macrovesicular

Increased trigliceride-synthesis Impraired trigliceride-excretion

- hyperlipidemias - impaired protein synthesis

- increased fatty acid synthesis - alcoholism

- decreased fatty acid oxidation (disturbed membrane transport)

(hypoxia, acidosis) - shortage of lipotropic materials

Characteristic localizations: LIVER, heart (diffuse, or „tiger heart”), kidney

Normal tissue

Abnormal noxas

degeneration adaptation

hyperplasia

hypertrophy

hyperplasia + hypertrophy

necrosis

death

superinfection

tissue loss

mutilation

resorption

cavitation

fistule

pseudocyst

Reparation

fibrosis

scarring

calcification

ossification

metaplasia

inflamm. atrophy

pseudometaplasia

pseudo-hypertrophy

regeneration

dysplasia

malignant transformation

((

Atrophy

Decrease of the size of organs, accompanied by decreased function

Physiologic atrophy = involution (thymus, breast, ovaries)

Local: Generalized:

- slow narrowing of arteries - senile atrophy

- loss of trophic effects - decreased food supply

- inactivity (muscles, bones) (inanition, malabsorption,

- loss of hormonal effects (adrenal) esophageal tumors)

side effects of steroids! - generalized atherosclerosis

- compression atrophy - tumorous cachexia

- irradiation - hypophysis-insufficiency

--vitamin B12 deficiency (tongue) - anorexia nervosa

- prolonged chronic inflammation (gastritis)

- degenerative processes (brain)

Conditions following atrophy

- function loss

- regeneration: after cessation of the cause

- pseudometaplasia (due to compression; e.g. flattening of columnar epithelium)

- space replace (fat, liquor)

- pseudohypertrophy: overproliferation of other tissues

- compensatory hypertrophy: (paired organs)

(loss of both the organic and inorganic material)

Diffuse Local

Primary Secondary (immobilisation)

- senile - glycocorticoids

- postmenopausal - hypogonadism

- malabsorption

- chr. alkoholism

Normal

CompressionNORMAL

POROTIC

Osteoporosis

Hydrocephalus, hydronephrosis

Cushing-syndrome

N

Celiac disease

(gluten-sensitive enteropathy)

genetic disposition + gluten exposition

starch + gluten

wheat

villi

Lieberkühn-

crypts

4

1

NORMAL

CELIAC DISEASE

Celiac disease

Celiac disease

MALABSORPTION

Alzheimer’s disease

- Most common cause of senile dementia

- Slowly progressive accumulation of a toxic, abnormal peptide

(A, -amyloid)

- Interference with neurotransmission

- Neuronal destruction

Normal tissue

Abnormal noxas

degeneration adaptation

hyperplasia

hypertrophy

hyperplasia + hypertrophy

necrosis

death

superinfection

tissue loss

mutilation

resorption

cavitation

fistule

pseudocyst

Reparation

fibrosis

scarring

calcification

ossification

metaplasia

inflamm. atrophy

pseudometaplasia

pseudo-hypertrophy

regeneration

dysplasia

malignant transformation

((

Hyperplasia

Increase of size of organs due to numerical excess of the cells

Prolonged demand

Organs /tissues that are capable of division

Prerequisite: good blood supply

Causative factors:

- hormonal effects (adrenal cortex, prostata, male breast, acromegaly)

- prolonged antigenic stimulus (follicular hyperplasia)

- drugs (cyclosporin A – gingival hyperplasia)

- metabolic causes (obesity)

- compensatory

- unknown

Hypertrophy

Increase in size of the organ, but the number of cells is unchanged

Tissue that are non capable of division (muscle)

Characteristically: against increased forces

Increased diameter of te cells, increased DNA content

Striated muscle (physical activity, sports)

Heart muscle

left chamber: hypertension, aortic stenosis

right chamber: increased pulmonary resistance (cor pulmonale chr.)

Congenital pylorus-stenosis

Hypertrophia of the urinary bladder

Hirschsprung-disease

Normal tissue

Abnormal noxas

degeneration adaptation

hyperplasia

hypertrophy

hyperplasia + hypertrophy

necrosis

death

superinfection

tissue loss

mutilation

resorption

cavitation

fistule

pseudocyst

Reparation

fibrosis

scarring

calcification

ossification

metaplasia

inflamm. atrophy

pseudometaplasia

pseudo-hypertrophy

regeneration

dysplasia

malignant transformation

((

Metaplasia

A mature tissue is replaced by an other mature tissue

Indirect metaplasia (abnormal differentiation of reserve cells)

Epithelial metaplasia:

glandular epithelium squamous epithelium (squamous metaplasia) – bronchus,cervix, pancreas

glandular epithelium another type of glandular epithelium (intestinal metaplasia)

(stomach; esophagus: Barrett-metaplasia; brest: apocrine metaplasia)

Mesenchymal metaplasia:

abnormal differentiation of pluripotent cells (cartilage, bone, etc.)