Pathology

Pathology: The study of the structural and functional changes leading to disease in:• Cell • Tissue • Organs

Pathophysiology: Is the abnormal function of organs or systems due to disease

Tools :• Molecular• Microbiological • Immunological • Morphological

Terminology

Pathology is divided

• General

• Special or systemic

General pathology:

Basic reaction of cells and tissue to normal stimuli

Specific pathology:

Specific response special organs to well defined stimuli

Terminology

1. Aetiology

2. Pathogenesis

3. Morphological changes

4. Clinical significance

Four aspects of disease process

A) Determining causeSpecifically known to be the soul cause of

disease such pathogenic organism e.g. HIV

B) Predisposing causesLeading indirectly to disease such as

genetic predisposition

1.Aetiology(Cause )

2.Pathogenesis

Is the mechanism by which a certain aetiological factor causes disease (In Greek: pathos = disease, genesis = development).

Some forms of pathogenesis are:Inflammation Malignancy Tissue breakdown

2.Pathogenesis

The pathogenesis process leads to the formation of lesion

Lesion is derived from the Latin word "laesio" which means "injury."

Lesions are a result of damage to tissues. For example:

A cancerous tumor is an example of a lesion

The surrounding tissue damaged by a tumour is also termed a lesion.

3.Morphological changes

Are the changes that occur in the cell tissue or organ as a result of the pathological process

These changes can be Morbid: Macroscopic appearance visible to the naked eye

3.Morphological changes

Are the changes that occur in the cell tissue or organ as a result of the pathological process

Or Histological : Microscopic appearance only visible under the

microscope

4.Clinical significance

What impact do these changes have on the patient?

Complete cure

Death

Complication Additional pathological changes which may

occur during or after the course of any disease

Progression of a disease

Pathological investigation

During life Surgical biopsyFine needle aspiration biopsy (FNAB)CytopathologyMolecular techniques

After deathAutopsy

Exposure to stress (irritant)

Mild irritant A) inflammationModerate B) Degeneration

Severe irritant Necrosis

Types of irritants

Living irritant:BacteriaPathogenic fungi Parasite Virus

Non-living irritant:Physical

Trauma, Burns, RadiationChemical

Acids, Alkalies Immunological

Ag-Ab reactionHypersensitivity reaction

Inflammation

It is the response of the living tissue to mild to moderate irritant

The response is directed to defend the tissue for foreign irritants and to prevent further damage

The aim is to bring more blood to the damaged area by acceleration of the blood stream

It is denoted by the suffix “itis”

Inflammation

Examples of inflammation Tonsillitis Appendicitis Tendonitis ,………etc.

Lung?

Inflammation

Exudate

An exudate is any fluid that filters from the circulatory system into lesions or areas of inflammation

Its composition varies but generally includes water and the dissolved solutes of the blood, some or all plasma proteins, white blood cells, platelets and RBC

Transudate

A fluid that passes through a membrane which filters out much of the protein and cellular elements to yield a watery solution.

A transudate is due to increased pressure in the veins and capillaries pressure forcing fluid through the vessel walls or low levels of protein the blood serum

The transudated fluid accumulates in tissues outside the blood vessels and can cause edema

Difference between exudates and transudate

Exudate transudate inflammation venous congestion

High above 4gm/m3 normalincreased normalhigh above 1018 normalturbid due to pnls clear+ve -ve

CauseProteinFibrinSGAppearanceFibrin clot

on standing

Types of Exudate

1. Serous exudate is usually seen in mild inflammation, with little protein content. seen in certain disease states like tuberculosis

2. Purulent or suppurative exudate consists of plasma with both active and dead neutrophils, fibrinogen, and necrotic parenchymal cells. referred to as pus.

3. Fibrinous exudate is composed mainly of fibrinogen and fibrin. It is characteristic of rheumatic carditis, but is seen in all severe injuries such as strep throat and bacterial pneumonia

4. Hemorrhagic exudate is seen in injury that causes rupture of blood vessels.

5. Pleural.

6. Catarrhal exudate is seen in the nose and throat and is characterized by a high content of mucus.

Inflammation

Effects of inflammation 1. Vascular phenomena

1. Transient vasoconstriction rapidly followed

2. Vasodilatation

3. Stasis

4. Migration of leucocytes

Inflammation

Effects of inflammation

2- Exudative stress

Emigration of leukocytes

Inflammation fluid exudate

Inflammation

Composition and function of inflammation fluid exudatesFluid exudates

Dilution of bacterial toxins fibrin threads : help the movement of leucocytes

and limit the spread of infection Also contain antibodies

Inflammation

Composition and function of inflammation fluid exudatesCellular part

Phagocytosis: engulfing of and destruction of bacteria and necrotic tissue by phagocytes and PNL

Inflammation

Chemotaxis: the movment of WBC in the area of inflammation towards the irritant

Emigration of leukocytes: the migration of WBC from within the blood vessel towards the inflammation site

Diapedesis: the passage and movment of

RBC from within the blood vessel towards the inflamed area

Cardinal signs of inflammation

Redness

Hotness

Swelling (edema) due to inflammatory exudate

Pain: due to pressure of edema on nerves and irritation of nerve ends by metabolites

Loss of function: this is to make the inflamed part of tissue rest and heal.

Types of inflammation

Acute inflammation Acute non-suppurative inflammation: acute without

the formation of pus Acute suppurative inflammation: with pus

Localized : Abscess, Furuncle, Carbuncle Diffused : cellulitis, septic meningitis

Chronic inflammation Chronic specific : TB Chronic non-specific: follows acute or chronic from

the beginning

Cells of inflammation

Acute inflammation cells:1- RBC 2- PNL (leukocyte)

Eosinophils

Basophils

Neutrophils

Chronic inflammation cells

1- lymphocytes

2- Plasma cells

3- Histocytes

4- fibroblasts

Cells of inflammation

Fate of acute inflammation 1- Regretion: by resolution for example when the body

(immunsystem) overcomes the bacterial infection 2- Progression which can lead to chronic inflammation

and spread: the bacteria overcome the immunsystem and can spread by :

Blood: septeciemia, bacterimea, toximia pyaemia

Lymphatyic: lyphangitis, lyphadenites

Direct to other surrounding tissue

Type of cells

Contentiously dividing cells (Labile): epithelium, haematopoietic (blood)

Quiescent (Stable): hepatic, kidney and pancreas

Non-dividing (Permanent): nerve cells and skeletal muscle cells

Cell development

Proliferation: increased number

Differentiation: development through stages

healing

Tissue repair involves replacement of damaged tissue with new healthy living tissue when resolution cannot occur

TypesUsually involves two separate but coordinated components

A) Regeneration:

healing by the same type of tissue cells from surrounding healthy living cells, this occurs with in small damages of labile cells and stable cells for examples liver cirrhosis and bone fractures

B) Fibros (scar tissue):

healing by granulation tissue (fibroblast with new capillaries formed) which mature a vascular fibrous tissue (scar), this occurs in the healing process of permanent cells and stable cells with high damage. for example myocardial infraction and wounds

Introduction to wond healing

Healing is a complex and dynamic process of restoring cellular structures and tissue layers.

The adult wound healing process can be divided into 4 distinct phases: The homeostasis phase the inflammatory phase the proliferative phase the remodeling phase.

Sequence of events in healing

Initial phase - Hemostasis

Following vasoconstriction, platelets adhere to damaged endothelium and discharge adenosine diphosphate (ADP), promoting thrombocyte clumping, which dams the Wound

The inflammatory phase is initiated by the release of numerous cytokines by platelets.

Fibrinogen is cleaved into fibrin and the framework for completion of the coagulation process is formed. Fibrin provides the structural support for cellular constituents of inflammation.

This process starts immediately after the insult and may continue for a few days

Sequence of events in healing

Second phase - Inflammation

Within the first 6-8 hours, the next phase of the healing process is underway, with polymorphonuclear leukocytes (PMNs) or PNLs engorging the wound

These cells “cleanse” the wound, clearing it of debris. The PMNs attain their maximal numbers in 24-48 hours and commence their departure by hour 72

As the process continues, monocytes also exude from the vessels. These are termed macrophages. The macrophages continue the cleansing process and manufacture various growth factors during days 3-4.

Many factors influencing the wound healing process are secreted by macrophages. These include TGFs, cytokines and interleukin-1 (IL-1), tumor necrosis factor (TNF)

Sequence of events in healing

Third phase - Granulation This phase consists of different subphases. These subphases do not happen in discrete time frames but

constitute an overall and ongoing process. The subphases are: fibroplasia matrix deposition angiogenesis and re-epithelialization

In days 5-7, fibroblasts have migrated into the wound, laying down new collagen of the subtypes I and III

The wound is suffused with GAGs and fibronectin that are bonded covalently to a protein core and contribute to matrix deposition

Angiogenesis is the product of parent vessel offshoots. The formation of new vasculature requires extracellular matrix and basement membrane degradation followed by migration, mitosis, and maturation of endothelial cells

Re-epithelization occurs with the migration of cells from the periphery of the wound and adnexal structures. This process commences with the spreading of cells within 24 hours. Division of peripheral cells occurs in hours 48-72, resulting in a thin epithelial cell layer, which bridges the wound.

This succession of subphases can last up to 4 weeks in the clean and uncontaminated wound.

Sequence of events in healing

Fourth phase - Remodeling

After the third week, the wound undergoes constant alterations, known as remodeling,

This can last for years after the initial injury occurred. Collagen is degraded and deposited in an equilibrium-producing fashion

The collagen deposition in normal wound healing reaches a peak by the third week after the wound is created.

Contraction of the wound is an ongoing process resulting in part from the proliferation of the specialized fibroblasts termed myofibroblasts, which resemble contractile smooth muscle cells.

Types of healing

Types of healing

Types of healing

This process can go wrong and produce an increase of fibroblastic proliferation with a resultant hypertrophic scar

Further exuberance can result in keloid formation where scar production extends beyond the area of the original insult. Conversely, insufficient healing can result in atrophic scar formation.

Complications of the healing process

Complications of the healing process

Week scar: this may lead to hernia Cicatrisation: contracture of the size of the scar Implantation epidermiod cyst Stump neuroma: following amputation causing a painful

coiled mass of nerves Sinus: is a track of septic granulation tissue connecting a

cavity to the outside and has one blind end e.g. pilonidal sinus

Fistula: is a tract of septic granulation tissue connecting 2 epithelial surfaces

Infection : leading to delayed healing Rarely scars may develop squamous cell carcinoma Ulcers: discontinuity of cover epithelium or muscle

membrane

Bone: Introduction:Introduction:

Bone is a dynamic tissue Osteoblasts - osteoid (type 1 collagen) Calcium and phosphate (calcium

hydroxyapatite) Osteoclasts are multi-nucleated cells

which resorb bone (PTH).

Osteogenic cells:

Bone Anatomy

Diaphysis Metaphysis Epiphysis – Prox/Dist Epiphyseal line Periosteum Compact cortical bone Spongy bone Articular Cartilage Medullary cavity Marrow Nutrient artery

The Histologic Types:

Compact bone Spongy bone Lamellar bone Woven bone Osteoid Callus

The matrix of bone :

Contains inorganic salt Calcium Hydroxyapatite in collagen framework.

Osteoblasts - Calcification - Mineralization

Minerals hardnessCollagen fibres Tensile strength.Collagen is necessary for Calcification.

Fractures:

Break in the bone.Simple / Compound – infection.Single - Horizontal, oblique, spiral, Comminuted – multiple.Greenstick – partial children.Torus – compression of cortex –

children.

Types of Fracture:

Bone Remodeling

Vitamin D Nutrition Physical activity Age, hormones PTH, PHRP IL1, TNF,TGF-β

5-10% bone / year.

Stages of wound healing

Time after injury

Hemostasis

Inflammation

Proliferation

Resolution/ Remodeling

PMNs, Macrophages, Lymphocytes

Reepithelialization, Angiogenesis, Fibrogenesis,

Vessel regression, Collagen remodeling

Fibrin clot, platelet deposition

1D 3D 1wk 6wk 8wk

Healing in Bone:

1D - Hematoma formation (fibrin mesh) 3D - Inflammation 1W - Soft callus – granulation, matrix. 3-6W - Callus – ossification, woven bone 8+W - Re-modeling – absorb/deposit,

strength, lamellate.

Healing in Bone:

Healing in Bone:

Healing in Bone:

Healing in Bone:

Healing in Bone:

Factors affecting Healing:

Systemic & Local factorsImmobilization *Improper reduction – abnormal positionInfection. Debris, dead tissue in woundJoint involvement

Complications:

Delayed healing.Non healing.Joint involvement - ankylosisAbnormal position – arthritis.Bone necrosis – nutrient arteryInvolucrum formation.Pseudoarthrosis