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Introduction to pathology
subject: Roganidana
syllabus: paper 1- part A- III heading-1st point
Dr Ashwini S G BAMS MD(Ayu)
Assistant professor
ALNRMAMC
Koppa, Chikmagalur.
1
pathology Word meaning
Greek Word
Patho: Suffering
Logos: Study
2
Definition
● Pathology is, Scientific study of changes in the structure and function of the body in
disease.
● It deals with Causes, Effect, Mechanisms and Nature of disease.
● In other words, pathology consists of the abnormalities in normal anatomy (including
histology) and normal physiology owing to disease.
● Another commonly used term with reference to study of diseases is
‘pathophysiology’(patho=suffering, physiology=study of normal function).
● Pathophysiology, thus, includes study of disordered function (i.e. physiological changes)
and breakdown of homeostasis in diseases (i.e. biochemical changes).
3
pioneers of pathology
● The Caduceus representing ancient Greek gods is symbol of
medicine
● ‘Father of medicine’ is Hippocrates;
● ‘Father of modern medicine’ is Sir William Osler.
● ‘Father of pathology’ is Rudolf Virchow;
● ‘Father of CPCs’clinicopathological conferences- is
Giovanni B. Morgagni;
● ‘Father of museum’ is John Hunter;
● ‘Father of clinical pathology’ is Paul Ehrlich;
● ‘Father of blood transfusion’ is Karl Landsteiner;
● ‘Father of cytology’ is George N. Papanicolaou.
4
5
The role and significance of learning of pathology in clinical
medicine is quite well summed up by Sir William Osler (1849-
1919), acclaimed physician and teacher in medicine considered
as ‘Father of Modern Medicine’ by his famous quote “your
practice of medicine will be as good as is your understanding of
pathology”.
Need for study
● The discipline of pathology forms a vital bridge between initial learning phase of
preclinical sciences and the final phase of clinical subjects.
● Helps in providing final diagnosis of disease.
● knowledge and understanding of the language in the form of pathology
laboratory reports, otherwise doctor would not be able to institute appropriate
treatment or suggest preventive measures to the patient.
● In pathology, we study causes (etiology), mechanisms (pathogenesis) and arrive
at final diagnosis by various laboratory methods; gross and microscopic
examination of tissues is the major method.
6
Common Terminologies used
● Patient is the person affected by disease.
● Lesions are the characteristic changes in tissues and cells produced by disease
in an individual or experimental animal.
● Pathologic changes or morphology consist of examination of diseased tissues.
(microscopic or macroscopic).
7
-etiology- Causal factors responsible for the lesions. (i.e. ‘why’ of disease).
-pathogenesis of disease-Mechanism by which the lesions are produced. (i.e. ‘how’ of disease).
Symptoms -Functional implications of the lesion felt by the patient are symptoms.
Signs-Functional implications of the lesion those discovered by the clinician are the physical
signs.
Clinical significance of the morphologic and functional changes together with results of other
investigations help to arrive at an answer to what is wrong (diagnosis), what is going to happen
(prognosis), what can be done about it (treatment), and finally what should be done to avoid
complications and spread (prevention) (i.e. ‘what’ of disease).
8
EVOLUTION OF PATHOLOGY
Prehistoric Times-
● Religion, Magic and medical Treatment were linked to each other.
● Earliest concept -disease was the outcome of ‘Curse From God’ , Magic or ‘Evil Eye Of
Spirits.’
● To ward them off, priests through prayers and sacrifices, and magicians by magic power
used to act as faith-healers and invoke supernatural powers and please the gods.
9
● mythological Greeks- Aesclepius and Apollo as the principal gods of healing.
● Dhanvantri- as the deity of medicine in India, and
● orthodox Indians’ - Mata Sheetala Devi as the pox goddess.
10
Apollo
Asclepius
● Dhanvantari is the Hindu god of medicine and an avatar of
Lord Vishnu.
● He has been the king of Varanasi.
● He is mentioned in the Puranas as the god of Ayurveda.
● He, during the Samudramanthan arose from the Ocean of
Milk with the nectar of immortality.
● It is common practice in Hinduism for worshipers to pray to
Dhanvantari seeking his blessings for sound health for
themselves and/or others, especially on Dhanteras or
Dhanwantari Trayodashi "National Ayurveda Day- nov 2”.
11
● Shitala, is a Hindu goddess widely worshiped in the Indian subcontinent,
notably in North India.
● Shitala literally means "one who cools" in Sanskrit.
● As an incarnation of Supreme Goddess Parvati, she cures poxes, sores,
ghouls, pustules and diseases, acclaimed by Hindus.
● Goddess Sheetala is worshiped on the eighth day after festival of colours
(Holi), on the occasion of Sheetala Asthami.
● According to Skanda Purana, when the Gods performed a sacrificial fire
ceremony for Goddess Parvati, from that fire emerged Goddess Shitala,
who was seated on a donkey, holding a pot, and a silver broom, in her two
hands. Sometimes, she is said to be carrying a bunch of neem (Azadirachta
indica) leaves.
● At that moment, from Lord Shiva's sweat was born Jwarasura, who spread
disease all over the world. Goddess Shitala rid the world from the disease,
and from then onwards, Jwarasura became her servant.
12
● The insignia of healing, the Caduceus, having snake and staff, is
believed to represent the god Hermes or Mercury, which according to
Greek mythology has power of healing since snake has regenerative
powers expressed by its periodic sloughing of its skin.
● God of Greek medicine, Aesculapius, performed his functions with a
staff having a single serpent wound around it. Later (around AD1800),
however, the Caduceus got replaced with twin-serpents wound
around a staff topped by a round knob and flanked by two wings and
now represents the symbol of medicine instead of cross.
13
philosophical and rational approach
This happened at the time when great Greek philosophers—Socrates, Plato and
Aristotle,introduced philosophical and rational approach to the disease bye the methods of
observations.
14
Real practice of medicine
Began with hippocrates(460–370 BC), the great greek clinical genius of all times ‘thefatherof medicine’.
Hippocrates dissociated medicine from religion and magic.
He firmly believed in study of patient’s symptoms and described methods of diagnosis.
He recorded his observations on cases in the form of collections of writings called hippocraticcorpus which
remained the mainstay of learning of medicine for nearly two thousand years.
However, the prevailing concept at that time on mechanism of disease based on disequilibrium of four basic
humors (water, air, fire, and earth) was propagated by hippocates too but this concept was later abandoned.
15
● Hippocrates followed rational and ethical attitudes in practice and teaching of medicine
and is revered by the medical profession by taking ‘Hippocratic oath’ at the time of entry
into practice of medicine.
● In Rome, Hippocratic teaching was propagated by Roman physicians, notably by
Cornelius Celsus (53 BC-7 AD) and Claudius Galen (130–200 AD).
● Celsus first described four cardinal signs of inflammation—rubor (redness), tumor
(swelling), calor (heat), and dolor (pain).
● Galen postulated humoral theory, later called Galenic theory. This theory suggested that
the illness resulted from imbalance between four humors (or body fluids): blood, lymph,
black bile (believed at that time to be from the spleen), and biliary secretion from the
liver.
16
The hypothesis of disequilibrium of four elements constituting the body (Dhatus) similar to
Hippocratic doctrine finds mention in ancient Indian medicine books compiled about 200 AD—
Charaka Samhita, a finest document by Charaka on medicine listing 500 remedies, and
Sushruta Samhita, similar book of surgical sciences by Sushruta, and includes about 700 plant-
derived medicines.
At end of medival period-disease is because of sins, post moetem was prohibited.
Renaissance period i.e. revival of learning. (Italy in late 15th century) advances in art and
science. freedom of thought, philosophical and rational attitude.
17
Vesalius (1514–1564) Dissection on humam body on freshly executed criminals
Marcello Malpighi(1624–1694) presence of capillaries and described the malpighian layer of the skin,
and lymphoid tissue in the spleen (malpighian corpuscles). Malpighi is
known as ‘the father of histology.’
Giovanni B. Morgagni (1682–
1771).
700 postmortem - concept of clinicopathologic correlation (CPC),
establishing a coherent sequence of cause, lesions, symptoms, and
outcome of disease.
Sir Percivall Pott (1714–1788),
famous surgeon in England
Described arthritic tuberculosis of the spine (Pott’s disease)
identified the first ever occupational cancer (cancer of
scrotal skin) in the chimney sweeps in 1775 and discovered
chimney soot as the first carcinogenic agent
Edward Jenner (1749–1823) whose work on inoculation in smallpox is well known
Richard Bright (1789–1858) described non-suppurative nephritis, later termed glomerulonephritis or
Bright’s disease;
Thomas Addison (1793–1860) gave an account of chronic adrenocortical insufficiency termed Addison’s
disease;
18
Thomas Hodgkin (1798–1866) observed the complex of chronic enlargement of lymph nodes, often
with enlargement of the liver and spleen, later called Hodgkin’s
disease.
R.T.H. Laennec (1781–1826) French physician, (19th century-numerous discoveries).
Described several lung diseases (tubercles, caseous lesions, miliary
lesions, pleural effusion, and bronchiectasis), chronic sclerotic liver
disease (later called Laennec’s cirrhosis) and invented stethoscope.
F. von Rokitansky(1804–1878), self-taught German pathologist, performed nearly 30,000 autopsies
himself. He described acute yellow atrophy of the liver, wrote an
outstanding monograph on diseases of arteries and congenital heart
defects.
Louis Pasteur (1822–1895) French chemist, firmly established germ theory of disease.
G.H.A. Hansen (1841–1912) Identified Hansen’s bacillus in 1873 as the first microbe causative for
leprosy (Hansen’s disease)
Metchnikoff (1845-1916) a Russian zoologist, existance of phagocytosis by human defense
cells against invading microbes.
19
Paul Ehrlich (1854–1915) German physician, conferred Nobel prize in 1908 for his work in
immunology, described Ehrlich’s test for urobilinogen using Ehrlich’s
aldehyde reagent, staining techniques of cells and bacteria, and laid
the foundations of clinical pathology.
Christian Gram (1853–1938) Danish physician, developed bacteriologic staining by crystal violet.
D.L. Romanowsky (1861–
1921)
Russian physician, developed stain for peripheral blood film using
eosin and methylene blue derivatives.
Robert Koch (1843–1910) German bacteriologist, besides Koch’s postulate and
Koch’sphenomena, developed techniques of fixation and staining for
identification of bacteria, discovered tubercle bacilli in 1882 and
cholera vibrio organism in 1883.
May-Grünwald in 1902 and
Giemsa in 1914
Developed blood stains and applied them for classification of blood
cells and bone marrow cells.
Sir William Leishman (1865–
1926)
described Leishman’s stain for blood films in 1914 and observed
Leishman-Donovan bodies (LD bodies) in leishmaniasis.
20
Robert Feulgen
(1884–1955)
described Feulgen reaction for DNA staining and laid the foundations of cytochemistry
and histochemistry
Rudolf Virchow
(1821–1905)
microscopic examination of diseased tissue at cellular level and thus began
histopathology as a method of investigation.
(Virchow’s triad—slowing of blood-stream, changes in the vessel wall, changes in the
blood itself),
metastatic spread of tumours (Virchow’s lymph node), and components and diseases
of blood (fibrinogen, leukocytosis, leukaemia).
Karl Landsteiner
(1863–1943)
described the existence of major human blood groups in 1900 and is considered
“father of blood transfusion”; he was awarded Nobel prize in 1930
George N.
Papanicolaou
(1883–1962),
The development of exfoliative cytology for early detection of cervical cancer. Greek-
born, American pathologist, in 1930s and is known as ‘father of exfoliative cytology.
M.M. Wintrobe
(1901–1986),
Discovered haematocrit technique.
21
Modern pathology
Watson and Crick 1953 Description of the structure of DNA of the cell.
Tijo and Levan in 1956 Identification of chromosomes and their correct number in humans (46).
Nowell and Hagerford in
1960
Identification of Philadelphia chromosome t(9;22) in chronic myeloid leukaemia
as the first chromosomal abnormality in any cancer.
1969 In Situ hybridization (ISH) to detect and localise specific RNA or DNA
sequences ‘in situ’ (i.e. in the original place). later modified as fluorescence
microscopy (FISH) to detect specific localisation of the defect on chromosomes.
1972 Recombinant DNA technique developed using restriction enzymes to cut and
paste bits of DNA.
Kary Mullis in 1983 Introduction of polymerase chain reaction (PCR) i.e. “xeroxing” of DNA
fragments has revolutionised the diagnostic molecular genetics. PCR analysis
is more rapid than ISH, can be automated by thermal cyclers and requires much
lower amount of starting DNA.
22
Barbara
McClintock
Invention of flexibility and dynamism of DNA by for which she was awarded Nobel prize in
1983.
Ian Wilmut
and his
colleagues
1997
Mammalian cloning started at Roslin Institute in Edinburgh, by successfully using a technique
of somatic cell nuclear transfer to create the clone of a sheep named Dolly. Reproductive
cloning for human beings, however, is very risky besides being absolutely unethical.
2000s stem cell research by harvesting primitive cells isolated from embryos and maintaining their
growth in the laboratory. There are 2 types of sources of stem cells in humans: embryonic
stem cells and adult stem cells, the former being more numerous. Stem cells are seen by
many researchers as having virtually unlimited applications in the treatment of many human
diseases such as Alzheimer’s disease, diabetes, cancer, strokes, etc. At some point of time,
stem cell therapy may be able to replace whole organ transplant and instead stem cells
‘harvested’ from the embryo may be used.
April 2003 Human Genome Project (HGP) coinciding with DNA double helix by Watson and Crick in April
1953. The sequencing reveals that human genome contains approximately 3 billion base
pairs of amino acids, which are located in the 23 pairs of chromosomes within the nucleus of
each human cell. Each chromosome contains an estimated 30,000 genes in the human
genome which carry the instructions for making proteins. The HGP has given us the ability to
read nature’s complete genetic blueprint used in making of each human being (i.e. gene
mapping)
23
Divisions of pathology
1. General pathology: general principles of disease
a. Morphological branches
b. Non morphologival branches
2. Systemic pathology: study of diseases pertaining to the specific organs and body systems
24
There are three main subtypes of pathology:
•Anatomical pathology,
•Clinical pathology, and
•Molecular pathology.
Subdivisions of pathology
General pathology
1. Morphological branches: here, use of microscope as an
essential tool.
a. Histopathology
i. Surgical pathology
ii. Experimental pathology
iii. Forensic pathology and atopsy work
b. Hematology
c. Cytopathology
2. Non morphological branches:
a. Clinical pathology
b. Clinical biochemistry
c. Microbiology
d. Immunology
e. Medical genetic
f. Molecular pathology
25
Systemic Pathology:
1. Respiratory system
2. Cardiovascular system pathology
3. Gastrointestinal system pathology
4. Hematological system pathology
5. Nervous system
6. Urogenital system pathology
7. Immune system pathology
8. Diseases of breast
9. Endocrine system
10. Skeletal system
11. Exocrine system
A. HISTOPATHOLOGY/ Anatomic Pathology/ Pathologic Anatomy/ Morbid Anatomy/ Tissue
Pathology:
classic method of study and still the most useful one.
The study includes
● Gross or macroscopic changes,
● and by microscopy,
which may be further supported by numerous special staining methods such as
● Histochemistry And
● Immunohistochemistry to arrive at the most accurate diagnosis.
Modern time anatomic pathology includes sub-specialities such as cardiac pathology, pulmonary pathology,
neuropathology, renal pathology, gynaecologic pathology, breast pathology, dermatopathology,
gastrointestinal pathology, oral pathology and so on.
26
Morphological branch
27
Subdivisions of Histopathology
Surgical
pathology:
•The study of tissues
removed from the
living body by biopsy
or surgical resection.
(forms the bulk of
tissue material for
the pathologist).
•Includes study of
tissue by
conventional paraffin
embedding
technique; intra-
operative frozen
section may be
employed for rapid
diagnosis.
Experimental
Pathology:
•This is defined as
production of disease in
the experimental animal
and study of
morphological changes
in organs after sacrificing
the animal
•However, all the findings
of experimental work in
animals may not be
applicable to human
beings due to species
differences.
Forensic pathology and Autopsy
work:
•The study of organs and tissues removed at
post-mortem for medicolegal work and for
determining the underlying sequence
and cause of death.
•By this, the pathologist attempts to
reconstruct the course of events how they
may have happened in the patient during
life which culminated in his death.
•Post-mortem anatomical diagnosis is
helpful to the clinician to enhance his
knowledge about the disease and his
judgement
•Forensic autopsy is helpful for medico
legal purposes. The significance of a
careful post-mortem examination is
appropriately summed up in the old
saying ‘the dead teach the living’.
B. HAEMATOLOGY
● Haematology deals with the diseases of blood.
● It includes ;
○ laboratory haematology and (eg: LFT- liver function test,
Hemoglobin count)
○ clinical haematology; (which covers the management of patient as
Well) (eg: blood transfusion in hemolytic anemia).
28
C. CYTOPATHOLOGY
● A branch of anatomic pathology,
● cytopathology has developed as a distinct
subspecialty in recent times.
● It includes study of cells of superficial and deep-
seated lesions for diagnosis from;
○ Cells shed off from the lesions (Exfoliative
cytology) and
○ Fine-needle Aspiration Cytology (FNAC)
29
30
31
32
NON-MORPHOLOGICAL BRANCHES
1. Clinical pathology
2. Clinical biochemistry
3. Microbiology
4. Immunology
5. Medical genetics
6. Molecular pathology
33
•In these diagnostic branches, qualitative, semi-quantitative or quantitative
determinations are carried out in the laboratory. Microscope may also be
required for at least some of these lab tests.
Qualitative Analysis:
● To Establish the
presence or absence of
particular organic
compounds or functional
groups in an
unknown sample. ...
For example,
● A medical technician
might test a
urine sample to
determine if glucose is
present.
● Another example would
be observing that a
reaction is creating gas
that is bubbling out of
solution or observing
that a reaction results in
a colour change. 34
Semi Quantitative
Analysis:
•Qualitative and semi-
quantitative examinations are
those that give non-numerical
results.
•Qualitative examinations
measure the presence or
absence of a substance, or
evaluate cellular characteristics
such as morphology.
•Semi-
quantitative examinations
provide an estimate of how
much of the measured
substance is present.
Quantitative
analysis:
• To determine the
amounts of chemical
substances that may be
contained in a wide
variety of samples.
•Example, you could test for
the presence of alcohol in
the blood (qualitative),
and/or may test for the
actual blood alcohol level
(quantitative).
A. CLINICAL PATHOLOGY ( clinical chemistry)
● Analysis of various fluids including blood, urine, semen, CSF and
other body fluids is included in this branch of pathology.
● Such analysis may be qualitative, semi-quantitative or quantitative.
Example: CBC- complete blood count, urine analysis etc.
35
● Quantitative determination of various biochemical constituents in serum and plasma and
in other body fluids is included in clinical biochemistry.
● Obviously, there is likely to be overlapping between clinical pathology and clinical
biochemistry.
Example:
● Serum. Serum is the most common specimen tested - it is obtained by centrifugation of
coagulated blood. ...
● Plasma. Plasma is obtained by centrifugation of uncoagulated blood. ...
● Urine. ...
● Cerebrospinal spinal fluid (CSF) ...
● Carbohydrates. ...
● Lipids. ...
● Enzymes. ...
● Hormones
36
B. CLINICAL BIOCHEMISTRY
C. MICROBIOLOGY
● This is study of disease-causing microbes implicated in human diseases.
● Depending upon the type of microorganism studied, it has further
developed into such as bacteriology, parasitology, mycology, virology etc.
● Microbiologists tended to specialize in one of several subfields.
For example,
● Bacteriology is the study of Bacteria;
● Mycology is the study of Fungi;
● Protozoology is the study of Protozoa; and
● Virology is the study of Viruses
37
D. IMMUNOLOGY
● Detection of abnormalities in the
immune system of the body
comprises immunology and
immunopathology.
38
The diverse scope of this laboratory's services
encompasses patient evaluation for atopy,
immunodeficiences, acute and chronic
infections, autoimmune disorders, complement
function, and suitability as allograft recipients
The Division of Clinical Immunopathology offers a wide range of clinical immunologic testing procedures for diagnosis
and monitoring of diseases where the pathogenesis involves components of the immune system. These include:
● Serologic analyses for evaluation of antibodies to identify infectious diseases.
● Electrophoretic analysis of serum and urine to detect monoclonality of immunoglobulins and immunofixation for
characterization of monoclonal proteins.
● Analysis of serum, urine and cerebrospinal fluids for quantitative and qualitative immunoglobulin abnormalities
● Isoelectric focusing for detecting cerebral spinal fluid immunoglobulin abnormalities
● Nephelometric quantitation (This test specifically measures the immunoglobulins IgM, IgG, and IgA) of serum and
cerebral spinal fluid proteins involved in the immunopathogenesis of disease.
● Allergen-specific immunoglobulin testing for allergies.
● Detection and characterization of autoantibodies in the evaluation of connective tissue and autoimmune diseases
● Confirmatory serologic testing for diagnosis of HIV infection
● Serological testing for hepatitisA, B and C
● Analysis and characterization of cryoglobulins
● Diagnostic procedures for syphilis, toxoplasma, mycoplasma
● Detection of disease-specific antibodies for measles, mumps, rubella, varicella zoster, herpes simplex
● Detection of tuberculosis infection (Gene-Xpert, a CBNAAT (catridge based nucleic acid amplification test) is a
widely accepted diagnostic test for Tuberculosis. This test is a rapid diagnostic test for Tuberculosis detection as
well as Rifampicin resistance in direct smear negative cases).
39
E. MEDICAL GENETICS
● This is the branch of human genetics that deals with the relationship between
heredity and disease.
● There have been important developments in the field of medical genetics e.g.
○ in blood groups, inborn errors of metabolism,
○ chromosomal aberrations in congenital malformations and neoplasms etc.
40
F. MOLECULAR PATHOLOGY
● The detection and diagnosis of abnormalities at the level of DNA of the cell is
included in molecular pathology such as in situ hybridisation, PCR etc.
● These methods are now not only used for research purposes but are also being
used as a part of diagnostic pathology reports.
41
42
● The divisions of pathology into several subspecialties are quite
artificial since overlapping of disciplines is likely,
● ultimate aim of pathologist being to
○ establish the final diagnosis and
○ learn the causes and mechanisms of disease.
● Towards this aim, the beginner as well as the teacher in
pathology remain life-long students of pathology, eager to learn
more in their quest to become better with every passing day.
43
● Ref: Harshmohan text book of pathology
44

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Introduction to pathology.pptx

  • 1. Introduction to pathology subject: Roganidana syllabus: paper 1- part A- III heading-1st point Dr Ashwini S G BAMS MD(Ayu) Assistant professor ALNRMAMC Koppa, Chikmagalur. 1
  • 2. pathology Word meaning Greek Word Patho: Suffering Logos: Study 2
  • 3. Definition ● Pathology is, Scientific study of changes in the structure and function of the body in disease. ● It deals with Causes, Effect, Mechanisms and Nature of disease. ● In other words, pathology consists of the abnormalities in normal anatomy (including histology) and normal physiology owing to disease. ● Another commonly used term with reference to study of diseases is ‘pathophysiology’(patho=suffering, physiology=study of normal function). ● Pathophysiology, thus, includes study of disordered function (i.e. physiological changes) and breakdown of homeostasis in diseases (i.e. biochemical changes). 3
  • 4. pioneers of pathology ● The Caduceus representing ancient Greek gods is symbol of medicine ● ‘Father of medicine’ is Hippocrates; ● ‘Father of modern medicine’ is Sir William Osler. ● ‘Father of pathology’ is Rudolf Virchow; ● ‘Father of CPCs’clinicopathological conferences- is Giovanni B. Morgagni; ● ‘Father of museum’ is John Hunter; ● ‘Father of clinical pathology’ is Paul Ehrlich; ● ‘Father of blood transfusion’ is Karl Landsteiner; ● ‘Father of cytology’ is George N. Papanicolaou. 4
  • 5. 5 The role and significance of learning of pathology in clinical medicine is quite well summed up by Sir William Osler (1849- 1919), acclaimed physician and teacher in medicine considered as ‘Father of Modern Medicine’ by his famous quote “your practice of medicine will be as good as is your understanding of pathology”.
  • 6. Need for study ● The discipline of pathology forms a vital bridge between initial learning phase of preclinical sciences and the final phase of clinical subjects. ● Helps in providing final diagnosis of disease. ● knowledge and understanding of the language in the form of pathology laboratory reports, otherwise doctor would not be able to institute appropriate treatment or suggest preventive measures to the patient. ● In pathology, we study causes (etiology), mechanisms (pathogenesis) and arrive at final diagnosis by various laboratory methods; gross and microscopic examination of tissues is the major method. 6
  • 7. Common Terminologies used ● Patient is the person affected by disease. ● Lesions are the characteristic changes in tissues and cells produced by disease in an individual or experimental animal. ● Pathologic changes or morphology consist of examination of diseased tissues. (microscopic or macroscopic). 7
  • 8. -etiology- Causal factors responsible for the lesions. (i.e. ‘why’ of disease). -pathogenesis of disease-Mechanism by which the lesions are produced. (i.e. ‘how’ of disease). Symptoms -Functional implications of the lesion felt by the patient are symptoms. Signs-Functional implications of the lesion those discovered by the clinician are the physical signs. Clinical significance of the morphologic and functional changes together with results of other investigations help to arrive at an answer to what is wrong (diagnosis), what is going to happen (prognosis), what can be done about it (treatment), and finally what should be done to avoid complications and spread (prevention) (i.e. ‘what’ of disease). 8
  • 9. EVOLUTION OF PATHOLOGY Prehistoric Times- ● Religion, Magic and medical Treatment were linked to each other. ● Earliest concept -disease was the outcome of ‘Curse From God’ , Magic or ‘Evil Eye Of Spirits.’ ● To ward them off, priests through prayers and sacrifices, and magicians by magic power used to act as faith-healers and invoke supernatural powers and please the gods. 9
  • 10. ● mythological Greeks- Aesclepius and Apollo as the principal gods of healing. ● Dhanvantri- as the deity of medicine in India, and ● orthodox Indians’ - Mata Sheetala Devi as the pox goddess. 10 Apollo Asclepius
  • 11. ● Dhanvantari is the Hindu god of medicine and an avatar of Lord Vishnu. ● He has been the king of Varanasi. ● He is mentioned in the Puranas as the god of Ayurveda. ● He, during the Samudramanthan arose from the Ocean of Milk with the nectar of immortality. ● It is common practice in Hinduism for worshipers to pray to Dhanvantari seeking his blessings for sound health for themselves and/or others, especially on Dhanteras or Dhanwantari Trayodashi "National Ayurveda Day- nov 2”. 11
  • 12. ● Shitala, is a Hindu goddess widely worshiped in the Indian subcontinent, notably in North India. ● Shitala literally means "one who cools" in Sanskrit. ● As an incarnation of Supreme Goddess Parvati, she cures poxes, sores, ghouls, pustules and diseases, acclaimed by Hindus. ● Goddess Sheetala is worshiped on the eighth day after festival of colours (Holi), on the occasion of Sheetala Asthami. ● According to Skanda Purana, when the Gods performed a sacrificial fire ceremony for Goddess Parvati, from that fire emerged Goddess Shitala, who was seated on a donkey, holding a pot, and a silver broom, in her two hands. Sometimes, she is said to be carrying a bunch of neem (Azadirachta indica) leaves. ● At that moment, from Lord Shiva's sweat was born Jwarasura, who spread disease all over the world. Goddess Shitala rid the world from the disease, and from then onwards, Jwarasura became her servant. 12
  • 13. ● The insignia of healing, the Caduceus, having snake and staff, is believed to represent the god Hermes or Mercury, which according to Greek mythology has power of healing since snake has regenerative powers expressed by its periodic sloughing of its skin. ● God of Greek medicine, Aesculapius, performed his functions with a staff having a single serpent wound around it. Later (around AD1800), however, the Caduceus got replaced with twin-serpents wound around a staff topped by a round knob and flanked by two wings and now represents the symbol of medicine instead of cross. 13
  • 14. philosophical and rational approach This happened at the time when great Greek philosophers—Socrates, Plato and Aristotle,introduced philosophical and rational approach to the disease bye the methods of observations. 14
  • 15. Real practice of medicine Began with hippocrates(460–370 BC), the great greek clinical genius of all times ‘thefatherof medicine’. Hippocrates dissociated medicine from religion and magic. He firmly believed in study of patient’s symptoms and described methods of diagnosis. He recorded his observations on cases in the form of collections of writings called hippocraticcorpus which remained the mainstay of learning of medicine for nearly two thousand years. However, the prevailing concept at that time on mechanism of disease based on disequilibrium of four basic humors (water, air, fire, and earth) was propagated by hippocates too but this concept was later abandoned. 15
  • 16. ● Hippocrates followed rational and ethical attitudes in practice and teaching of medicine and is revered by the medical profession by taking ‘Hippocratic oath’ at the time of entry into practice of medicine. ● In Rome, Hippocratic teaching was propagated by Roman physicians, notably by Cornelius Celsus (53 BC-7 AD) and Claudius Galen (130–200 AD). ● Celsus first described four cardinal signs of inflammation—rubor (redness), tumor (swelling), calor (heat), and dolor (pain). ● Galen postulated humoral theory, later called Galenic theory. This theory suggested that the illness resulted from imbalance between four humors (or body fluids): blood, lymph, black bile (believed at that time to be from the spleen), and biliary secretion from the liver. 16
  • 17. The hypothesis of disequilibrium of four elements constituting the body (Dhatus) similar to Hippocratic doctrine finds mention in ancient Indian medicine books compiled about 200 AD— Charaka Samhita, a finest document by Charaka on medicine listing 500 remedies, and Sushruta Samhita, similar book of surgical sciences by Sushruta, and includes about 700 plant- derived medicines. At end of medival period-disease is because of sins, post moetem was prohibited. Renaissance period i.e. revival of learning. (Italy in late 15th century) advances in art and science. freedom of thought, philosophical and rational attitude. 17
  • 18. Vesalius (1514–1564) Dissection on humam body on freshly executed criminals Marcello Malpighi(1624–1694) presence of capillaries and described the malpighian layer of the skin, and lymphoid tissue in the spleen (malpighian corpuscles). Malpighi is known as ‘the father of histology.’ Giovanni B. Morgagni (1682– 1771). 700 postmortem - concept of clinicopathologic correlation (CPC), establishing a coherent sequence of cause, lesions, symptoms, and outcome of disease. Sir Percivall Pott (1714–1788), famous surgeon in England Described arthritic tuberculosis of the spine (Pott’s disease) identified the first ever occupational cancer (cancer of scrotal skin) in the chimney sweeps in 1775 and discovered chimney soot as the first carcinogenic agent Edward Jenner (1749–1823) whose work on inoculation in smallpox is well known Richard Bright (1789–1858) described non-suppurative nephritis, later termed glomerulonephritis or Bright’s disease; Thomas Addison (1793–1860) gave an account of chronic adrenocortical insufficiency termed Addison’s disease; 18
  • 19. Thomas Hodgkin (1798–1866) observed the complex of chronic enlargement of lymph nodes, often with enlargement of the liver and spleen, later called Hodgkin’s disease. R.T.H. Laennec (1781–1826) French physician, (19th century-numerous discoveries). Described several lung diseases (tubercles, caseous lesions, miliary lesions, pleural effusion, and bronchiectasis), chronic sclerotic liver disease (later called Laennec’s cirrhosis) and invented stethoscope. F. von Rokitansky(1804–1878), self-taught German pathologist, performed nearly 30,000 autopsies himself. He described acute yellow atrophy of the liver, wrote an outstanding monograph on diseases of arteries and congenital heart defects. Louis Pasteur (1822–1895) French chemist, firmly established germ theory of disease. G.H.A. Hansen (1841–1912) Identified Hansen’s bacillus in 1873 as the first microbe causative for leprosy (Hansen’s disease) Metchnikoff (1845-1916) a Russian zoologist, existance of phagocytosis by human defense cells against invading microbes. 19
  • 20. Paul Ehrlich (1854–1915) German physician, conferred Nobel prize in 1908 for his work in immunology, described Ehrlich’s test for urobilinogen using Ehrlich’s aldehyde reagent, staining techniques of cells and bacteria, and laid the foundations of clinical pathology. Christian Gram (1853–1938) Danish physician, developed bacteriologic staining by crystal violet. D.L. Romanowsky (1861– 1921) Russian physician, developed stain for peripheral blood film using eosin and methylene blue derivatives. Robert Koch (1843–1910) German bacteriologist, besides Koch’s postulate and Koch’sphenomena, developed techniques of fixation and staining for identification of bacteria, discovered tubercle bacilli in 1882 and cholera vibrio organism in 1883. May-Grünwald in 1902 and Giemsa in 1914 Developed blood stains and applied them for classification of blood cells and bone marrow cells. Sir William Leishman (1865– 1926) described Leishman’s stain for blood films in 1914 and observed Leishman-Donovan bodies (LD bodies) in leishmaniasis. 20
  • 21. Robert Feulgen (1884–1955) described Feulgen reaction for DNA staining and laid the foundations of cytochemistry and histochemistry Rudolf Virchow (1821–1905) microscopic examination of diseased tissue at cellular level and thus began histopathology as a method of investigation. (Virchow’s triad—slowing of blood-stream, changes in the vessel wall, changes in the blood itself), metastatic spread of tumours (Virchow’s lymph node), and components and diseases of blood (fibrinogen, leukocytosis, leukaemia). Karl Landsteiner (1863–1943) described the existence of major human blood groups in 1900 and is considered “father of blood transfusion”; he was awarded Nobel prize in 1930 George N. Papanicolaou (1883–1962), The development of exfoliative cytology for early detection of cervical cancer. Greek- born, American pathologist, in 1930s and is known as ‘father of exfoliative cytology. M.M. Wintrobe (1901–1986), Discovered haematocrit technique. 21
  • 22. Modern pathology Watson and Crick 1953 Description of the structure of DNA of the cell. Tijo and Levan in 1956 Identification of chromosomes and their correct number in humans (46). Nowell and Hagerford in 1960 Identification of Philadelphia chromosome t(9;22) in chronic myeloid leukaemia as the first chromosomal abnormality in any cancer. 1969 In Situ hybridization (ISH) to detect and localise specific RNA or DNA sequences ‘in situ’ (i.e. in the original place). later modified as fluorescence microscopy (FISH) to detect specific localisation of the defect on chromosomes. 1972 Recombinant DNA technique developed using restriction enzymes to cut and paste bits of DNA. Kary Mullis in 1983 Introduction of polymerase chain reaction (PCR) i.e. “xeroxing” of DNA fragments has revolutionised the diagnostic molecular genetics. PCR analysis is more rapid than ISH, can be automated by thermal cyclers and requires much lower amount of starting DNA. 22
  • 23. Barbara McClintock Invention of flexibility and dynamism of DNA by for which she was awarded Nobel prize in 1983. Ian Wilmut and his colleagues 1997 Mammalian cloning started at Roslin Institute in Edinburgh, by successfully using a technique of somatic cell nuclear transfer to create the clone of a sheep named Dolly. Reproductive cloning for human beings, however, is very risky besides being absolutely unethical. 2000s stem cell research by harvesting primitive cells isolated from embryos and maintaining their growth in the laboratory. There are 2 types of sources of stem cells in humans: embryonic stem cells and adult stem cells, the former being more numerous. Stem cells are seen by many researchers as having virtually unlimited applications in the treatment of many human diseases such as Alzheimer’s disease, diabetes, cancer, strokes, etc. At some point of time, stem cell therapy may be able to replace whole organ transplant and instead stem cells ‘harvested’ from the embryo may be used. April 2003 Human Genome Project (HGP) coinciding with DNA double helix by Watson and Crick in April 1953. The sequencing reveals that human genome contains approximately 3 billion base pairs of amino acids, which are located in the 23 pairs of chromosomes within the nucleus of each human cell. Each chromosome contains an estimated 30,000 genes in the human genome which carry the instructions for making proteins. The HGP has given us the ability to read nature’s complete genetic blueprint used in making of each human being (i.e. gene mapping) 23
  • 24. Divisions of pathology 1. General pathology: general principles of disease a. Morphological branches b. Non morphologival branches 2. Systemic pathology: study of diseases pertaining to the specific organs and body systems 24 There are three main subtypes of pathology: •Anatomical pathology, •Clinical pathology, and •Molecular pathology.
  • 25. Subdivisions of pathology General pathology 1. Morphological branches: here, use of microscope as an essential tool. a. Histopathology i. Surgical pathology ii. Experimental pathology iii. Forensic pathology and atopsy work b. Hematology c. Cytopathology 2. Non morphological branches: a. Clinical pathology b. Clinical biochemistry c. Microbiology d. Immunology e. Medical genetic f. Molecular pathology 25 Systemic Pathology: 1. Respiratory system 2. Cardiovascular system pathology 3. Gastrointestinal system pathology 4. Hematological system pathology 5. Nervous system 6. Urogenital system pathology 7. Immune system pathology 8. Diseases of breast 9. Endocrine system 10. Skeletal system 11. Exocrine system
  • 26. A. HISTOPATHOLOGY/ Anatomic Pathology/ Pathologic Anatomy/ Morbid Anatomy/ Tissue Pathology: classic method of study and still the most useful one. The study includes ● Gross or macroscopic changes, ● and by microscopy, which may be further supported by numerous special staining methods such as ● Histochemistry And ● Immunohistochemistry to arrive at the most accurate diagnosis. Modern time anatomic pathology includes sub-specialities such as cardiac pathology, pulmonary pathology, neuropathology, renal pathology, gynaecologic pathology, breast pathology, dermatopathology, gastrointestinal pathology, oral pathology and so on. 26 Morphological branch
  • 27. 27 Subdivisions of Histopathology Surgical pathology: •The study of tissues removed from the living body by biopsy or surgical resection. (forms the bulk of tissue material for the pathologist). •Includes study of tissue by conventional paraffin embedding technique; intra- operative frozen section may be employed for rapid diagnosis. Experimental Pathology: •This is defined as production of disease in the experimental animal and study of morphological changes in organs after sacrificing the animal •However, all the findings of experimental work in animals may not be applicable to human beings due to species differences. Forensic pathology and Autopsy work: •The study of organs and tissues removed at post-mortem for medicolegal work and for determining the underlying sequence and cause of death. •By this, the pathologist attempts to reconstruct the course of events how they may have happened in the patient during life which culminated in his death. •Post-mortem anatomical diagnosis is helpful to the clinician to enhance his knowledge about the disease and his judgement •Forensic autopsy is helpful for medico legal purposes. The significance of a careful post-mortem examination is appropriately summed up in the old saying ‘the dead teach the living’.
  • 28. B. HAEMATOLOGY ● Haematology deals with the diseases of blood. ● It includes ; ○ laboratory haematology and (eg: LFT- liver function test, Hemoglobin count) ○ clinical haematology; (which covers the management of patient as Well) (eg: blood transfusion in hemolytic anemia). 28
  • 29. C. CYTOPATHOLOGY ● A branch of anatomic pathology, ● cytopathology has developed as a distinct subspecialty in recent times. ● It includes study of cells of superficial and deep- seated lesions for diagnosis from; ○ Cells shed off from the lesions (Exfoliative cytology) and ○ Fine-needle Aspiration Cytology (FNAC) 29
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  • 31. 31
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  • 33. NON-MORPHOLOGICAL BRANCHES 1. Clinical pathology 2. Clinical biochemistry 3. Microbiology 4. Immunology 5. Medical genetics 6. Molecular pathology 33 •In these diagnostic branches, qualitative, semi-quantitative or quantitative determinations are carried out in the laboratory. Microscope may also be required for at least some of these lab tests.
  • 34. Qualitative Analysis: ● To Establish the presence or absence of particular organic compounds or functional groups in an unknown sample. ... For example, ● A medical technician might test a urine sample to determine if glucose is present. ● Another example would be observing that a reaction is creating gas that is bubbling out of solution or observing that a reaction results in a colour change. 34 Semi Quantitative Analysis: •Qualitative and semi- quantitative examinations are those that give non-numerical results. •Qualitative examinations measure the presence or absence of a substance, or evaluate cellular characteristics such as morphology. •Semi- quantitative examinations provide an estimate of how much of the measured substance is present. Quantitative analysis: • To determine the amounts of chemical substances that may be contained in a wide variety of samples. •Example, you could test for the presence of alcohol in the blood (qualitative), and/or may test for the actual blood alcohol level (quantitative).
  • 35. A. CLINICAL PATHOLOGY ( clinical chemistry) ● Analysis of various fluids including blood, urine, semen, CSF and other body fluids is included in this branch of pathology. ● Such analysis may be qualitative, semi-quantitative or quantitative. Example: CBC- complete blood count, urine analysis etc. 35
  • 36. ● Quantitative determination of various biochemical constituents in serum and plasma and in other body fluids is included in clinical biochemistry. ● Obviously, there is likely to be overlapping between clinical pathology and clinical biochemistry. Example: ● Serum. Serum is the most common specimen tested - it is obtained by centrifugation of coagulated blood. ... ● Plasma. Plasma is obtained by centrifugation of uncoagulated blood. ... ● Urine. ... ● Cerebrospinal spinal fluid (CSF) ... ● Carbohydrates. ... ● Lipids. ... ● Enzymes. ... ● Hormones 36 B. CLINICAL BIOCHEMISTRY
  • 37. C. MICROBIOLOGY ● This is study of disease-causing microbes implicated in human diseases. ● Depending upon the type of microorganism studied, it has further developed into such as bacteriology, parasitology, mycology, virology etc. ● Microbiologists tended to specialize in one of several subfields. For example, ● Bacteriology is the study of Bacteria; ● Mycology is the study of Fungi; ● Protozoology is the study of Protozoa; and ● Virology is the study of Viruses 37
  • 38. D. IMMUNOLOGY ● Detection of abnormalities in the immune system of the body comprises immunology and immunopathology. 38 The diverse scope of this laboratory's services encompasses patient evaluation for atopy, immunodeficiences, acute and chronic infections, autoimmune disorders, complement function, and suitability as allograft recipients
  • 39. The Division of Clinical Immunopathology offers a wide range of clinical immunologic testing procedures for diagnosis and monitoring of diseases where the pathogenesis involves components of the immune system. These include: ● Serologic analyses for evaluation of antibodies to identify infectious diseases. ● Electrophoretic analysis of serum and urine to detect monoclonality of immunoglobulins and immunofixation for characterization of monoclonal proteins. ● Analysis of serum, urine and cerebrospinal fluids for quantitative and qualitative immunoglobulin abnormalities ● Isoelectric focusing for detecting cerebral spinal fluid immunoglobulin abnormalities ● Nephelometric quantitation (This test specifically measures the immunoglobulins IgM, IgG, and IgA) of serum and cerebral spinal fluid proteins involved in the immunopathogenesis of disease. ● Allergen-specific immunoglobulin testing for allergies. ● Detection and characterization of autoantibodies in the evaluation of connective tissue and autoimmune diseases ● Confirmatory serologic testing for diagnosis of HIV infection ● Serological testing for hepatitisA, B and C ● Analysis and characterization of cryoglobulins ● Diagnostic procedures for syphilis, toxoplasma, mycoplasma ● Detection of disease-specific antibodies for measles, mumps, rubella, varicella zoster, herpes simplex ● Detection of tuberculosis infection (Gene-Xpert, a CBNAAT (catridge based nucleic acid amplification test) is a widely accepted diagnostic test for Tuberculosis. This test is a rapid diagnostic test for Tuberculosis detection as well as Rifampicin resistance in direct smear negative cases). 39
  • 40. E. MEDICAL GENETICS ● This is the branch of human genetics that deals with the relationship between heredity and disease. ● There have been important developments in the field of medical genetics e.g. ○ in blood groups, inborn errors of metabolism, ○ chromosomal aberrations in congenital malformations and neoplasms etc. 40
  • 41. F. MOLECULAR PATHOLOGY ● The detection and diagnosis of abnormalities at the level of DNA of the cell is included in molecular pathology such as in situ hybridisation, PCR etc. ● These methods are now not only used for research purposes but are also being used as a part of diagnostic pathology reports. 41
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  • 43. ● The divisions of pathology into several subspecialties are quite artificial since overlapping of disciplines is likely, ● ultimate aim of pathologist being to ○ establish the final diagnosis and ○ learn the causes and mechanisms of disease. ● Towards this aim, the beginner as well as the teacher in pathology remain life-long students of pathology, eager to learn more in their quest to become better with every passing day. 43
  • 44. ● Ref: Harshmohan text book of pathology 44