Introduction to Pathology

By Gandi Li

Department of Pathology

West China Medical School

Where there is love of medicine, there is love of humankind.

-- Hippocrates

(460-377 BC)

The most common diseases in developing countries

Infectious diseases (viral hepatitis, tuberculosis, bacterial pneumonia, bacterial diarrheas, AIDS, et al)

Atherosclerosis and hypertension

Cancer

Emphysema and chronic bronchitis

What happens in Nepal?

Disease could reasonably be defined as internal problems that cause pain and/or interfere with a person's ability to work, play, and/or love others. Pathology is the scientific study of disease. Now more and more people know many diseases are lifestyle-related.Pathology is a bridge between medicine and basic sciences for medical students.Pathology is also one of the most important methods to diagnose disease in clinical practice.

Pathology involves

Etiology (causes of diseases,Why?)

Pathogenesis (mechanisms, How?)

Pathological changes (lesions, What?) Morphological changes (anatomical pathology) Functional changes (pathophysiology)

Clinical manifestations (signs and symptoms)

Sequelae (healing, complications, death)

Branchs of pathologyGeneral pathology cell injury tissue repair hemodynamic disord

ers inflammation tumor

Systemic pathology the blood vessels and

the heart the respiratory system the digestive system the urinary system the male and female

genital system the nervous system the endocrine system

GOAL of PATHOLOGY GOAL of PATHOLOGY for MEDICAL STUDENTSfor MEDICAL STUDENTS

Be able to understand and analyze the relationship between pathologic changes and clinical manifestations.Be able to take a clinical history and order tests logically.Be able to develop a correct diagnosis.Be able to communicate with professionals and patients.Does become a physician or a pathologist?

Physician or surgeon mostly.

What does a PATHOLOGIST do?

SURGICAL PATHOLOGY Interpret biopsies (e.g., skin, breast, gastroi

ntestinal tract)Evaluate surgical resection specimens (e.

g., colectomy, nephrectomy, mastectomy)Frozen sections (intra-operational rapid dia

gnosis)

What does a PATHOLOGIST do?

CYTOPATHOLOGY (e.g., Pap smears, FNA - Fine Needle Aspiration)CLINICAL PATHOLOGY Hematology (Peripheral blood smear, bone marrow,

coagulation disorders). Chemistry (Blood, urine, cerebrospinal fluid, effusions). Microbiology. Blood bank.

AUTOPSY PATHOLOGY Final diagnosis, forensic pathology--criminal

investigation

How to study pathology?

Background:

Basic medical sciences (anatomy, histology, physiology, biochemistry, immunology, microbiology, parasitology,et al)

Medical terms (e.g. hyperplasia, et al)

Clinical knowledge (physical examination, laboratory tests, X-ray, CT, et al)

How to study pathology?

The key for studying pathology:

Characteristic

morphologic lesions (lesions)

Clinical manifestations

PathogenesisEtiology

FunctionalChanges(Pathophysiology)

How to study pathology?

Approach to good result:Lectures and textbooksLaboratory practice: gross specimen and glass slidesClinicopathologic conference (CPC)Autopsy demonstration (real or video)Recommend internet web sites: http://www-medlib.med.utah.edu/webPath/webpath.html

Observation of gross specimen:a hypertrophic heart (left) and a normal heart (right)

Gross observation of a nutmeg liver and mircoscopic changes

Cancer cells in ascites of a patient with gastric carcinoma

Summary of introduction

The terms disease pathology general patholog

y lesion pathologist surgical pathology

The roles of pathology in medical education and clinical practice

How to study pathology Uebung machts Master. (Practice trains master) Arbeit machts Spass! (Work brings happy!)

A famous painting about autopsy by Rhunbrant in 18 century

“As is our pathology, so is our medicine”

“Ask not what disease the patient has, but rather what patient the disease has.”

Sir William Osler (Canadian Physician)

Cell Injury, Adaptation and Death

Overview of cell injury

Causes of cell injury

Mechanisms of cell injury

Cellular adaptation to injury

Reversible and irreversible cell injury

Programmed cell death---- apoptosis

Cellular aging

Overview of cell injury

Homeostasis requires functional cooperation in widely distributed cells.

Normal cells homeostasis

Adaptativecells

Reversibleinjured cells

Cell death

necrosisapoptosisatrophy,

hypertrophyhyperplasiametapllasia

LethalReversible

Lethal

Reversible

Reversible

intracellular accumulations, degenerationA summary of the relationship between normal cells,

adaptative cells, reversible injured cells and cell death

The relationship between cellular function, cell death andthe morphologic changes of cell injury.

Causes of cell injury

Ischemia/hypoxia (e.g. heart attack)Chemical agents (toxins, acid, drugs) Active oxygen species: free radicals, oxidants, electrop

hiles

Infectious agents (bacterial, virus, parasite)Immunologic reactions (hypersensitivity)Genetic defects (Down’s syndrome)Nutritional imbalances (protein insufficiency)Physical agents (trauma, temperature)Aging

Mechanisms of cell injury

ATP depletion

Oxygen deprivation or generation of reactive oxygen species

Loss of calcium homeostasis

Defects in plasma membrane permeability

Mitochondria damage

Mechanism

of ischemic and hypoxic

injury

Cell mechanisms of injury

Free radicals/ reactive chemicals

Normalmetabolisms

O 2

OH•

H2O2

NO

SOD/CatalaseGlutathiole peroxidase/GSSG

Vitamin E, C

Detoxification

Cell membraneMitochondriaEndo. Retic.DNA

Neutralization of free radicals

SOD

2O2 + 2H+ H2O 2 + O2 catalase

2H2O2 2H2O + O2

glutathione peroxidase

2OH• + 2GSH GSSH + 2H2O glutathione reductase

SummaryAny stimuli and stresses can result in cell injuries.The injurious consequences depend on not only the type of injury, its duration, its severity, and also the type, status, adaptability and genetic makeup of the injured cell. Cell injury can be divided into reversible and irreversible.The loss of cell function is far before the cell death, but the morphological visible changes appear far behind the cell death.

Cellular adaptation to injury

Concept of Adaptation: When cells encounter physiologic stresses or

pathologic stimuli from outside and inside of body, they can alter themselves to achieve a new steady state and preserve viability.All kinds of adaptation may be considered as disorders of growth and/or differentiationCellular adaptation can be considered as a state between the normal, unstressed cell and injured, overstressed cell.

Atrophy

Definition: (briefly, decrease in cell size) Shrinkage in the size of the parenchymal cells b

y loss of cell substances in a well developed organ or tissue is known as atrophy. Or:acquired shrinkage of cells, tissues or organs.Simple atrophy (loss of cell size only)Numerous atrophy (loss of cell size and number through apoptosis)Differentiation: aplasia, hypoplasia

Testis:Right: Atrophied Left: Normal

There are kidneys and ureters of a one-year-old boy. The right Kidney is hypoplastic and the left one with a three-ureters abnormality.

Atrophy

The reasons of atrophy: Decreased workload disuse atrophy Loss of innervation neuropathic atrophy Diminished blood supply ischemic atrophy

press atrophy Absence of nutrition undernourished

atrophy Loss of hormone stimuli endocrine atrophy Aging senile atrophy

Brain atrophy in an old patient with arteriosclerosis. Note thewidened sulci and narrow convolutions.

Brain atrophy in a patient with Alzheimer’s disease. The gyri are narrowed and the sulci widened toward to frontal pole.

Hydrocephalus (left) and nephrohydrosis (right)Note the dilated ventricles and thinner grey and whine matter. The renal calyces and renal pelvis are dilated too.

There are some skeletal muscle fibers. The number of cells is the same as before the atrophy occurred, but the size of some fibers is reduced. In this case, innervation of the small fibers in the center was lost. This is a trichrome stain.

Atrophy

The atrophied cells, tissue and organ have Reduction of physiologic functions Decreased synthesis Increased catabolism—increased protein degradat

ion through

Lysosomes digest the senescent organelles (autolysis)

If the number of cells decrease, there is apoptosis (cell suicide), or programmed cell death

Hypertrophy

Definition: (briefly: increase in cell size)

an increase in the size of parenchymal cells and consequently an increase in the size of the organ.

No increase of cellnumber in a purified

hypertrophy!

Hypertrophy

Compensatory hypertrophy Mechanical stimuli---skeletal muscle of a sportsma

n Increased workload---left ventricle hypertrophy of s

ystemic hypertension Decompensation---heart failure

Endocrine hypertrophy Hormonal stimuli---pregnant uterus

---Cushing’s syndrome

Hypertrophy of left ventricle (centripetal hypertrophy) in a patient with essential hypertension. Note the marked thickened wall of ventricle.

a. Hypertrophy of the left ventricleb. Normal myocardial fibersc. Hypertrophic myocardial fibers

A pregnant uterus (right) and normal uterus (left)

Physiologic hypertrophy of the uterus during pregnancy.Left: gross appearance of a normal uterus and a gravid uterus.Middle: small spindle-shaped uterine smooth muscle cells fromA normal uterus. Right: large, plump hypertrophied smooth muscle cells froma gravid uterus.

Cushing’s syndrome resulted from adenoma of adrenal cortex

Hypertrophy

Hypertrophic cells and organ with Increased function Increased synthesis of structural protein Induced by two types of signals

Mechanical triggers----stretchTrophic triggers----activation of alpha-adrenergi

c receptors

Differentiate fromhyperplasia, pseudohypertrophy

Hyperplasia

Definition: (briefly, increase in cell number)An increase in the number of parenchymal cells in an organ or tissue.Hyperplasia can occur with hypertrophy in various tissue except muscles.Hyperplasia can be divided into Physiologic hyperplasia

Hormonal: breast glandular epithelium at pregnancy Pathologic hyperplasia

Compensatory: liver after partial resection

Hyperplasia of endometrium in an adult woman with menorrhagia

Examples of hyperplasia:

Red bone marrow of blood donor

Examples of hyperplasia:

Hyperadrenalism

Examples of hyperplasia:

Goiter (absence of iodine)

Hyperplasia of prostatic gland

Note the prostate isnodular enlarged

Hyperplasia

Hyperplasia is induced by stimulation of hormonal or growth factors, cytokines and chemokines through the signal transduction pathway

Hyperplasia can turn off when the organ restores or the stimulus stops

Continuous pathologic hyperplasia constitutes a fertile soil for cancerous proliferation

MetaplasiaDefinition: (briefly: change in cell type)A reversible change in which one adult cell type is replaced by another adult cell type.This replacement is through hyperplasia of “stem cell” or “undifferentiated cell”, so metaplasia is actually an abnormal hyperplasia.The significances of metaplasia are To be able to withstand the stress better To be able to transform into a cancerous proliferati

on

Squamous metaplasia in bronchus in a heavy smoker

Squamous metaplasia of laryngeal respiratory epithelium in a heavy smoker

Columnar to squamous metaplasia: Barrett metaplasia inlower part of esophagus

Intestinal metaplasiain a patient with chronic atrophic gastritisNote the gobletcells

This is dysplasia. The normal squamous epithelium at the left transforms to a disorderly growth pattern at the right. This is farther down the road toward neoplasia.

Summary of adaptation

Enlargement of an organ can result from Hypertrophy Hyperplasia Hypertrophy with hyperplasia Pseudohypertrophy (actual atrophy) Edema Tumor Congestion Inflammation

Summary of adaptation

Shrinkage of an organ can result from Atrophy Aplasia and hypoplasia

Hyperplasia persists only for so long as the stimulus is applied. When it is removed, the hyperplastic tissue tends to revert to its normal size.Hyperplasia must be distinguished from dysplasia and neoplastic proliferation.

Summary of adaptation

Metaplasia is an abnormal hyperplasia.It can become a malignant neoplasm.

All kind of adaptation can be considered as abnormal growth and/or differentiationAdaptation is the result of long time persisted, but mild stimuliMost adaptations are reversible when the stimulus is removed

Metaplasia

Normal cells

Dysplasia Malignant tumor

Simpleatrophy

Numerousatrophy

Hypertrophy Hyperplasia

adaptation

Sum

mary of abnorm

al grow

th

Learn words

Greek derivation:

dys- bad, abnormal

hyper- above, excessive

hypo- below, deficient

meta- beyond, between

-plasia a forming

-trophe nourishment

Requirements

The overview of cell injuries

The main mechanisms of cell injury Ischemia/hypoxia free radicals

Concepts and recognition of lesions Adaptation Atrophy Hypertrophy Hyperplasia Metaplasia

Give samples of various forms of adaptation and understand their significances

Thank you for your attention!