Surgical Pathology Fundamentals

Adapted from “Pathology” by Kansas State University

Concorde Career College, PortlandST120

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

Terminology

Cell structure

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. Etiology

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 as a pathogenic organism, e.g., HIV

B) Predisposing causesLeading indirectly to disease such as

genetic predisposition

1.Etiology

2.Pathogenesis

Is the mechanism by which a certain etiological 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 a 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 tumor 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 biopsy Fine needle

aspiration biopsy (FNAB)

Cytopathology Molecular techniques

After death Autopsy

Exposure to stress (irritant)

Mild irritant A) inflammationModerate B) Degeneration

Severe irritant Necrosis

Necrosis

Types of irritants

Living irritant:BacteriaPathogenic fungi Parasite VirusHelminths

Non-living irritant:Physical

Trauma, Burns, RadiationChemical

Acids, Alkalies Immunological

Ag-Ab reactionHypersensitivity reaction

Chemical burns

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?

Tonsillitis

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

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.

Purulent Exudate

Inflammation

Effects of inflammation Vascular phenomena

1. Transient vasoconstriction rapidly followed by

2. Vasodilatation

3. Stasis

4. Migration of leucocytes

Inflammation

Composition and function of inflammatory 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 inflammatory fluid exudatesCellular part

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

Inflammation

Chemotaxis: the movment of WBCs 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 movement of RBCs from within the blood vessel towards the inflamed area

Cardinal signs of inflammation

Redness (rubor)

Hotness (calor)

Edema (tumor) swelling due to inflammatory exudate

Pain (dolor) due to pressure of edema on nerves and irritation of nerve endings by metabolites

Loss of function (functio laesa) 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

Leukocyte review

http://en.wikipedia.org/wiki/White_blood_cell

Neutrophil engulfing anthrax bacteria

Cells of inflammation

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

(immune system) overcomes bacterial infection 2- Progression: can lead to chronic inflammation and

spread; the bacteria overcome the immune system and can spread by:

Blood: septicemia, bacteremia, toxemia pyemia

Lymphatyic: lymphangitis, lymphadenitis

Direct: to other surrounding tissue

Type of cells

Labile cells: 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 following damage to labile cells and stable cells, for example, liver cirrhosis and bone fractures

B) Fibrous (scar tissue):

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

Introduction to wound 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: Hemostasis phase Inflammatory phase Proliferative phase 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.

Sequence of events in healing

Third phase – Proliferation This phase consists of different subphases.

Fibroplasia Matrix deposition Angiogenesis Reepithelialization

During days 5-7, fibroblasts have migrated into the wound, laying down new collagen.

The wound is suffused with GAGs and fibronectin that are bonded 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.

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

Types of healing

Primary vs. secondary 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

Hypertrophic scar

Keloid

Complications of the healing process

Weak scar: this may lead to hernia Cicatrisation: contracture of the size of the scar Implantation epidermoid 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

Anal fistula

Bone

Bone is a dynamic tissue OsteoblastsOsteocytesOsteoclasts

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 Trabecular bone Lamellar bone Woven bone 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 boneSimple / Compound – infectionSingle - Horizontal, oblique, spiral, Comminuted – multipleGreenstick – partial childrenTorus (buckle) – compression of cortex

– children

Types of fractures

Compound fracture

Bone remodeling

Healing in bone

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

strengthen, lamellate

Healing in bone

Healing in bone

Healing in bone

Healing in bone

Healing in bone

Callus formation

Following mid-shaft humeral fracture

Factors affecting healing

Systemic & local factors

Immobilization Improper reduction –

abnormal position Infection: debris &

dead tissue in wound Joint involvement

Complications

Delayed healingNon healingJoint involvement - ankylosisAbnormal position – arthritisBone necrosis – nutrient artery

Avascular necrosisInvolucrum formationPseudarthrosis

Involucrum