Rog Nidan Basic Pathology –Part 2

Rog Nidan- Basic Pathology –Part 2

• Presented By – Prof.Dr.R.R.Deshpande (M.D in Ayurvdic Medicine & M.D. in Ayurvedic Physiology)

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12/21/2016 1Prof.Dr.R.R.Deshpande

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Rog Nidan –Basic Pathology

• This PPT is based on the –

• Syllabus of CCIM ( 2014) for 3rd BAMS of Rognidan

• Points are from Paper 1 Part A ,Point III – Basic Pathology


Basic Pathology

• 1. Introduction to pathology and its sub-divisions

• 2. Introduction to Cell Injury and Cellular adaptations

• 3. Definition and brief description of inflammation – Healing/repair


Contents of this PPT

• Definition and brief description of –

• Inflammation

• Healing & repair

12/21/2016 Prof.Dr.R.R.Deshpande 4

Inflammation – Definition

• This is a nonspecific local response to injury

• This defense mechanism helps to eliminate or to control the spread of injurious agents.


Inflammation

Pneumonitis Cervicitis


Injurious agents

• i) Physical Agents -- Heat (sun stroke) cold (frost bite) radiation.

• ii) Chemical Agents -- Poison

• iii) Infective Agents -- Bacteria, viruses• iv) Immunological Agents -- Antigen, antibody complex.


Signs of Inflammation



• i) Rubor – redness.• ii) Tumor – Swelling

• iii) Calor – Heat

• iv) Dolor – Pain• v) Functio laesa – loss of function.




Types of Inflammation

• i) Acute

• ii) Chronic


Acute Inflammation

• Short Duration – Usually atomatic repair• Changes divided into• 1) Vascular changes• 2) Cellular changes• Vascular Events -- • a) Hemodynamic changes• b) Altered Vascular permeability


Acute Inflammation

• a) Haemodynamic changes -- • i) Transient Vasoconstriction of arterioles -- The blood flow may be re established in 5 sec. to 5 min.

• ii) Persistent progressive vasodialatation – It is observed in the first half an hour of injury – Transudation of fluid in ECF (Extra Cellular fluid)


Acute Inflammation

• a) Haemodynamic changes –

• iii) Slowing or Stasis

• iv) Leukocytic migration -- Leukocytes stick to vascular endothelium & then move & migrate through the gaps between endothelial cells into ECF. This is called Emigration


b) Altered Vascular Permeability

• Due to vasodilatation – Fluid comes out from Blood plasma, so accumulation of oedema fluid, around the injured tissue.

• This fluid is transudate. Generally little fluid is taken up by lymphatics and no oedema occurs.

• If the trauma is severe – more fluid come out and lymphatics can not take it back naturally & oedema occurs


2) Cellular Events

• a) Exudation of leucocytes –

• The polymorphonuclear neutrophils (PMNs) comprise the 1st line of defense, followed by monocytes and macrophages.


b) Margination and pavementing

• Due to stasis and increased permeability, the layer of plasma close to vessel wall goes out into ECF and so the central stream of cells come in close contact with the cell wall

• This phenomenon is known as Margination or Pavementing.


Margination and pavementing


Emigration

• Neutrophils move along the wall of capillary to find suitable place to escape from vessel

• Then they put the out of the capillary wall and then stick to the outer surface of capillary

• With the help of pseudopodia, Neutrophill migrates into EC. This is Emigration.


Emigration of Neutrophil


Dipediasis

• After neutrophills, escape of RBCs through the gaps between endothelial cells is called Dipediasis

• This dipediasis give haemorrhagic appearance to inflammatory exudates.


Diapedesis


Chemotaxis

• Emigration due to some chemical stimuli in called chemotaxis

• Many chemicals liberated at the site of injury brings about Chemotaxis


Chemotaxis


Phagocytosis – Definition

• Process of engulfment of solid material by Phagocytes. ( e.g Specific cells like Kuffer’s cells in liver)

• Divided in 3 stages --- see Next Slides


Phagocytosis


1 ) Stage of Attachment

• Microorganisms and Neutrophills both are negative, so naturally they repeal each other

• Hence bacteria get coated with some specific substances (Opsonins),from serum

• e.g. i) IgE opsonin ii) C3b opsonin.


2 ) Stage of Engulfment

• Opsonised particle is now ready for engulfment

• There is formation of pseudopoda by phagocyte around the particle, enveloping it in a vacuole

• The plasma membrane from cellular surface break and thus the particle enters inside cell.


3 ) Stage of killing and degradation

• There are some antibacterial substances inside the cell, which kill the engulfed bacteria

• Killed bacteria then degraded by lysosomes of the Phagocytic cells

• This mechanism fails in some cases like Tubercle bacilli


Chemical Mediators of Acute Inflammation

• These are classified into –

• 1) Mediators released by cells of injured tissue

• 2) Mediators from plasma


I) Mediators released by cells of injured tissue

• i) Vasoactive amines -- a) Histamine:• Secreted by Eosinophil. It’s main function is vasodilation, it increases the vascular permeability. It also act as a neurotransmitter, which helps in the conduction of itching sensation.

• In the majority of the allergic reactions it is one of the transmitter

• so antihistaminic drugs like AVIL is used in the treatment.



• b) 5 – hydroxy tryptamine (5-HT) –

• It is same as histamine but is less potent.

• It is present in gastro intestinal tract and in spleen.



• c) Prostaglandin -- The name is given because this substance initially found in human seminal fluid, but now it could be isolated from various body tissues.

• Names -- PGD2, PGE2, PGF2• Functions -- Vasodilatation & increase permeability


I)Mediators released by cells of injured tissue

• iv) Thromboxane A2• This is vasoconstrictor substance and its main function is platelet aggregation ( Fast healing of Cell injury )

• v) Leukotrienes (LTs) :• They are derived from leukocytes . Act as chemotatic agent. Also helps in smooth muscle contraction.



• vi) Lysosomal Enzymes

• Neutrophills and monocytes release these enzymes which help in degradation of bacterial wall and extra cellular component.



• vii) PAF (Platelet Activating Factor)• Released from basophill and mast cells .It’s main function is to aggregating the platelets.

• viii)Cytokines• Released by lymphocytes and monocytes & important mediators liberated by these cells are Tumor Necrosis Factor (TNF) & Interleukin 1


II) Chemical Mediators from Plasma

• The following four systems are inter linked and are derived from plasma in inflammatory reactions

• i) Kinin system• ii) Clotting system• iii)Fibrinolytic system• iv)Complement system• 12/21/2016 Prof.Dr.R.R.Deshpande 37

II)Chemical Mediators from Plasma

• Hagemen Factor (Factor No. XII) Plays a key role in an interaction of these 4 systems

• i) Kinin System –

• It generates bradykinin. It brings about slow contraction of smooth muscles.


II) Chemical Mediators from Plasma

• ii) Clotting System –

• Activated factor XII initiates the chain reaction of clotting.


II)Chemical Mediators from Plasma

• iii) Complement System --• Activation of complement system takes place by stimulation of antigen of by bacterial toxins

• Function: It release histamine from mast cells & acts as a chemotatic agent for leukocytes.

• e.g. C3a, C1a, C5a are working substances


The inflammatory Cells

• i) Neutrophills (Polymorphs): These are predominant in acute infections.

• Enzymes – Proteases & lysosomes• Function : i) Phagocytosis (hence Neutrophillia is common in bacterial infection)

• ii) Engulfment of antigen, antibody complex

• Normal Count -- 60 – 70 %



• ii) Eosinophil:• Eosinophils have the enzyme --Myeloperoxidase.

• Eosinophillia is seen in Tropical Eosinophillia, allergy, worms, skin diseases, and malignant lymphoma.

• Eosinopenia or disappearance can occur in high level of steroid.



• iii) Basophil -- • Basophils secrete heparin & histamines. They are similar to the mast cells

• Function: Useful in hypersensitivity reaction• Histamine is released by IgE sensitized basophills.



• iv) Lymphocyte -- These are present in lymph nodes & spleen.

• Antibodies are formed by B- lymphocytes.• T-lymphocytes are useful in cell mediated immune response.

• Function : These cells are more dominant in the late stage of acute inflammation. They also play a important role in chronic inflammation.



• v) Plasma Cells --• These cells are derived from B-lymphocytes. These are rich in RNA and gamma globulins & they are active in antibody synthesis.

• They are increased in immunological reactions e.g. Autoimmune response like Rheumatoid arthritis (RA), Hypersensitivity reactions, Allergies & in Multiple Myeloma.



• vi) Monocytes --• They constitutes 4 – 5 % of the total WBCs

• In addition to this they are present in the tissue in the form of macrophages (Kuffers cells in Liver)


Inflammatory Response

• A) Factors related with Organism: Following factors of an organism are important in an inflammation.

• i) Type of injury and infection- In the streptococcal infection the skin gives the response by producing the boil or furuncle.



• ii) Virulence of an organism –

• It is the capacity of an organism to harm the host cells.



• iii)Dose of an organism -- To produce the host cells damage the certain number of organisms are required and generally this is tested by culture grown on specific media and the sensitivity test is carried out

• Urine, Blood, Sputum & Stool samples are generally send for the culture sensitivity test.



• iv) Route of Entry --

• Vibrio cholerae causes cholera only when ingested and not when injected.


Factors Related to the host

• i) General health of the patient• ii) Immune status• iii) Leucopenia – It is observed in Steroid use especially in RA, Asthma, skin allergy & Nephrotic syndrome.

• iv) Site and type of the tissue --The spread of infection is rapid through the mucus membrane.

• 12/21/2016 Prof.Dr.R.R.Deshpande 51

Inflammation Exudate

• The nature of the secretion of the inflammation may be ---

• i) Serous

• ii) Purulent

• iii) Hemorrhagic, fibrinous T.B., cold abscess etc.


Morphology of Infection

• The lesions of an infections show the responses like -----

• i) Membrane formation• ii) Ulcer• iii) Suppuration• iv) Cellulitis• v) Bacterial Infection (Bacteraemia, septicaemia, pyemia)



• i) Membrane formation: Inflammatory response to specific toxins of bacteria e.g. Diphtheria produces the membrane which is the hallmark of the disease

• ii) Ulcer: In Ulcerative colitis there is an ulcer in the colon.


Membrane Formation & Ulcer

Diphtheria Ulcerative colitis



• iii) Suppuration: Pus formation. e.g. Staphylococcal abscess

• iv) Cellulitis: Diffused inflammation of soft tissue due to the enzyme hyaluronidase, which is released by some bacteria


Suppuration & Cellulitis

Staphylococcal Abscess Cellulitis



• v) Bacterial Infection –

• i) Bacteramia --- Presence of small number of bacteria in blood.

• Blood culture is done to detect Salmonella Typhi.


v) Bacterial Infection

• ii) Septicemia -- Presence of rapidly multiplying highly pathogenic bacteria in blood.e.g. bacilli of Plague.

• They develop fast systemic effects like toxaemia.

• iii) Pyaemia -- Dissemination of small septic thrombi in blood. They can form pyaemic abscess e.g. liver abscess.


Systemic Effects of Acute Inflammation

• i) Fever

• ii) Leukocytosis

• iii) Lymphangitis

• iv) Lymphadenitis


Fate of Acute Inflammation

• Acute inflammatory response may subside or convert into the chronic response

• Following are the stages of the inflammatory response

• Continued with Next slide --



• i) Resolution

• ii) Healing by Scarring

• iii) Suppuration

• iv) Chronic inflammation 12/21/2016 Prof.Dr.R.R.Deshpande 62


• i) Resolution -- • Complete return to normal tissue.• ii) Healing --• When destruction is more, that deficit can not be filled up by parenchymal tissue (normal tissue) . So fibrosis takes place. (e.g. burn, surgery)



• iii) Suppuration ---

• When pyogenic bacteria are the cause of acute inflammation, they results in severe necrosis ,which then leads to suppuration.



• iv) Chronic Inflammation –

• If the stimuli persist then the inflammation turns into the chronic form

• The chronic inflammation takes place in tubercular reaction


Chronic Inflammation – Definition

• This is a prolonged process --

• In which tissue destruction and inflammation occur at the same time


Chronic Inflammation - Causes

• i) Chronic inflammation occurs after acute inflammation

• Tissue destruction is an extensive and the small number of bacteria survives at the site of acute inflammation and then chronic inflammation take place. e.g. 'Osteomylitis'


Chronic Inflammation-Osteomyelitis


Chronic Inflammation - Causes

• ii) Recurrent attack of acute inflammation: e.g. Recurrent UTI may turn into chronic pyelonephritis

• iii) Chronic inflammation from the beginning -

• e.g. Mycobacterium tubercle.


Chronic Inflammation - Pyelonephritis


Features of Chronic Inflammation

• 1) Mononuclear Cell Infiltration --• Lesions are infiltrated with phagocytes (monocytes) and lymphoid cells. Macrophages are the most common cells

• 2) Tissue destruction or necrosis takes place


Features of Chronic Inflammation

• 3) Proliferative changes --- Proliferation of small blood vessels and fibroblast (fibrous tissue) is very common

• So formation of granulation tissue & healing by fibrosis occurs


Types of chronic Inflammation

• 1) Chronic Non-specific Inflammation:-- Non specific inflammatory cell infiltration .Ex is Osteomylitis

• 2) Chronic granulomatous inflammation e.g. T.B.


Food – useful to reduce Inflammation


Gramuloma

• Definition -- It is a circumscribed lesion, 1- mm in diameter composed by modified macrophages (epithelioid cells) and this granuloma is rimmed by lymphoid cells in periphery.

• Chronic Inflammation also has giant cells. (A fusion of adjacent epithelioid cells) They also follows same track of necrosis and fibrosis.


Healing

• Definition -- • It is defined as the body's response to injury to restore normal structure and function.

• There are mainly 3 phages• i) Regeneration• ii) Repair• iii) Contraction of wound


Healing

• 1) Regeneration –

• The original tissue healing and restoration when occurs with the parenchymal cells then the process is called as Regeneration.


Regeneration

• Regeneration mainly involves 3 types of cells

• i) Liable Cell –

• Under normal physiological condition, these cells continue multiply through out the life. e.g. Epidermal cells (skin cells)


1) Regeneration • ii) Stable Cell -- They loose their ability of proliferation after adolescence e.g. Parenchymal cells of liver. (But can multiply in response to appropriate stimuli in adult life)

• iii) Permanent Cells -- Loose their ability to proliferate around at the time of birth e.g. Neurons and cardiac muscle cells.


2) Repair

• When the tissue is replaced by the connective tissues which causes the fibrosis and scar formation then the process of healing is called as “Repair”

• This process has 2 stages• Continued in Next slide --


Repair

• 1) Granulation tissue formation –• i) Phase of inflammation: After trauma, blood clot is formed at the site of injury.

• The inflmmatory cells migrate to the site of injury and liberate chemical mediators of inflammation.

• Some chemicals are released through plasma also.• Monocytes , macrophages and Neutrophils are predominant at this phase.


Repair

• ii) Phase of clearance -- • Proteolytic enzymes are liberated from Neutrophils, autolytic enzymes are released from dead tissue and phagocytic activity is carried out by macrophages

• In this process the necrotic tissue, debris and RBCs are cleared


iii) Phase of Growth of Granulation Tissue

• It consists of ---- a) Angiogenesis -- Formation of new blood vessels, by the proliferation of endothelial cells from the margins of wound of neighboring blood vessels

• Initially they are solid buds but within few hours develop a lumen and start carrying blood. Soon they are differentiated into arterioles and venuoles


Angiogenesis



• b) Fibrous tissue Formation: The new fibroblast originates from fibrocytes.

• Collagen fibers begin to appear on 6th day. • As healing progresses, the number of proliferating fibroblasts and new vessels decreases.

• Gradually more and more collagen is formed and new blood vessels decreased.

• At last inactive looking scars is formed. (Cicatrisation)



• c) Contraction of Wound –

• Wound starts contracting after 3 days and is completed on 14th day

• Wound is reduced approximately 80 % of original size


Theories about contraction

• How does the wound contraction take place?

• It is a question for the scientists and the theories have established for the explanation of this question.

• some of the explanations are as follow-


Theories about contraction

• 1) Dehydration or drying of wounds

• 2) Contraction of collagen fibers

• 3) Appearance of myofibroblast in active granulation tissue


Wound Healing

• This is a classical example of regeneration and repair


Stages of wound healing


1) Primary Union or 1st Intension

• Features ----• This is a healing of external type of wounds

e.g. a) An uninfected wound.b) Surgically incised wound.c) Without much loss of tissue.d) Edges of wound -----approximated

by surgical sutures.


10 unions take place as follows

• i) Initial haemorrhage -- Bleeding clot Seal

• ii) Acute inflammatory response -- It is seen within 24 hours. Initially the polymorphs appear and then they are replaced by macrophages on 3rd day.



• iii) Epithelial changes ---Basal cells of epidermis start to proliferate towards the incised tissue or site

• Approximated wound is covered by a layer of epithelium within 48 hours.

• By 5th day new multilayered epidermis is formed.



• iv) Organisation --• By the 3rd day fibroblast appears in the wound area & by 5th day new collagen fibers start forming and continue till the wound heal. Within 1 month – 10 wound healing is completed.

• v) Suture Track -- Each suture track is a separate wound and follows like original wound.


2) 20 - Secondary Intension

• This is applicable for the following types of wound.

• i) Open wound with large tissue deficit and infected.

• ii) Extensive loss of tissue.• iii) Wound is not approximated (i.e. not sutured)

•


2) 20 Secondary Intension

• In above situations basic events of wound healing are similar to primary type of healing

• However the process is slow and

• The scar is generally ugly in appearance


Wound Healing


Wound Healing


Wound Healing


Complications of wound healing

• 1. Infection• 2. Implantation cyst.• 3. Pigmentation• 4. Deficient scar formation• 5. Incisional hernia• 6. Hypertrophied scar.• 7. Excessive contraction.• 8. Neoplasia.12/21/2016 Prof.Dr.R.R.Deshpande 100

Complications of wound Healing


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Rog Nidan Basic Pathology –Part 2