NEET MDS Lessons
General Pathology
HEALING
Definition. Replacement of damages tissue by healthy tissue. It is an attempt to restore the tissue to structural and functional normalcy.
Healing may be of 2 types
A. Regeneration.
B. Repair by granulation tissue.
A. Regeneration
Where the replacement is by proliferation of parenchymatous cells of type destroyed. This depends upon:
(1) Regenerative capacity of cells. Cells may be :
(a) Labile cells which are constantly proliferating to replace cells continuously shed off or destroyed
Epithelial cells of skin and lining surfaces.
Lymphoid and haemopoietic tissue.
(b) Stable cell. Cells mostly in resting-phase, but capable of dividing when necessary e.g.
- Liver and other parenchymatous and glandular cells.
- Connective tissue cells.
- Muscle cells have a limited capacity to divide.
(c) Permanent cell. These cells, once differentiated are not capable. of dividing e.g.-nerve
(2) The extent of tissue loss. If there is extensive destruction including disruption of the framework, complete.regeneration is not possible. even with labile an stable cell
B. Repair by granulation tissue
Granulation tissue is formed by proliferation of surrounding connective tissue elements. which migrate into the site to be repaired.
Granulation tissue formation seen in :
- Wound healing.
- Organisation of exudates.
- Thrombi.
- Infarcts.
- Haematomas.
The process of repair can be best studied in clean incised wounds, where there is .no or minimal tjssue loss or the_edges or the edges of the wound are approximated closely as in a surgical wound. This is called Primary union (healing by first intention).
1. The blood in the incised area clots and the fibrin binds the edges together.
2. During the first 24 hours, an acute inflammation sets in to .bring protein and phagocyte rich exudates to the site.
3. The superficial part of the clot get dry and dehydrated{scab). The surface epithelium proliferates just beyond the cut edges and the cells migrate-deep to dry scab. Epithelialisation is usually complete by 24- 48 hours.
4 Granulation tissue, with actively growing fibroblasts and capillary buds invades the clot (stage of vascularisation). These fibroblasts 'posses contractile myofibrils & hence are termed as myofibroblasts'.
5. Simultaneously, demolition of the debris and clot components takes place.
6 The granulation tissue initially lays down a mucopolysacharide rich ground substance
7.Reticulin and later collagen fibrils are formed by the fibroblasts (with 5 days)
8 with progressive maturation of collagen, some of the capiliary buds develop into arterioles and venules and majority of them are obliterated (stage of devascularisation).
9. With time (weeks to months) the tensile strength of the scar increases and it shrinks.
Secondary union (excised wound-healing by secondary intention).
1. Coagulum forms and fills the gap.
2. Inflammatory reaction is seen as in primary union but is more intense, as a lot more debris has to be removed. .
3. Epithelial proliferation starts covering the surface from the periphery by proliferation beyond the edges and migration under scab.
4.Debridement starts and simultaneously granulation tissue grows into the coagulum from the sides and base of the wound. This is much more exuberant than in primary union. The surface now looks red and granular.
5. Wound contraction. This is early contraction (starts after 3 days and is complete in 2 weeks) and must be differentiated from contraction after scar formation Wounds can contract by up to 80% of original size of that the gap to be filled is much reduced, resulting in faster healing with a smaller scar.
Wound contraction is probably caused by:
- Dehydration
- Collagen contraction.
- Granulation tissue contraction .(myofibroblasts).
The exact mechanism is not known.
6. Laying down of collagen.
7 Maturation to form a scar which later shrinks and devascularises.
Factors affecting wound healing
Wound healing is delayed by :
A. Local factors
1. Poor blood supply.
2. Adhesion to bony surfaces (e.g. over the tibia).
3. Persistent injurious agents (infective or particulate) results in chronicity of inflammation and ineffective healing. .
4. Constant movement (especially in fracture healing).
5. ionizing radiation (in contrast, ultraviolet rays hasten healing).
6. Neoplasia.
B. General factors
I. Nutritional deficiency, especially of.
(i) Protein
(ii) Ascorbic acid (Vitamin C).
(iii) Zinc
2. Corticoids adversely affect wound contraction and granulation tissue formation
(anabolic steroids have a favorable effect).
3. Low temperature.
4. Defects (qualitative or quantitative) in polymorphs and macrophages
.Complication of wound healing
1. Wound dehiscence
2. Infection
3. Epidermal inclusion (implantation) cysts.
4. Keloid formation
5. Cicatrisation resulting in contract Ires and obstruction(in hollow viscera).
6. Calcification and ossification.
7. Weak scar which could be a site for incisional hernia
8. Painful scar if it involves a nerve twig.
9. Rarely neoplasia (especially in burn scars).
THE PITUITARY GLAND
This is a small, bean-shaped structure that lies at the base of the brain within the confines of the sella turcica. It is connected to the hypothalamus by a "stalk," composed of axons extending from the hypothalamus. The pituitary is composed of two morphologically and functionally distinct components: the anterior lobe (adenohypophysis) and the posterior lobe (neurohypophysis). The adenohypophysis, in H&E stained sections, shows a colorful collection of cells with basophilic, eosinophilic or poorly staining ("chromophobic") cytoplasm.
Thalassaemia. Genetic based defect in synthesis of one of the normal chains.
Beta thalassaemia ---> reduced Hb A and increased HbF (α2, Y2) HBA2(α2)
Alpha thalassaemia ---> reduced Hb-A, Hb-A2 and Hb-F-with formation of Hb-H(β4) and Hb Barts (Y4).
Thalassaemia may manifest as trait or disease or with intermediate manifestation.
Features:
• Microcytic hypochromic RBC is in iron deficjency.
• Marked anisopoikilocytsis with prominent target cells.
• Reticulocytosis and nucleated RBC seen.
• Mongoloid facies and X-ray findings characteristic of marrow hyperplasia
• Decreased osmotic. fragility.
• Increased marrow iron (important difference from iron deficiency anaemia).
• Haemosiderosis, especially with repeated transfusions.
Diagnosis is by Hb electrophoresis and by Alkali denaturation test (for HbF).
Liver cirrhosis
It is a chronic, progressive diffuse process characterized by
a. Hepatocellular necrosis
b. Replacement by fibrosis and inflammation
c. Hyperplasia of surviving liver cells forming regenerating nodules
d. Vascular derangement.
All these changes lead to loss of the normal liver architecture.
Pathology of cirrhosis
At first the liver is enlarged or of normal size. Late in the disease, it is reduced in size and weight.
Consistency- Firm.
Colour -May be yellow (fatty change), red (congestion), green (cholestaisis), or pale gray (recent nodules due to absence of pigment).
Morphologically According to the size of these nodules, cirrhosis can be classified
Micronodular (regular) cirrhosis. Small nodules 2-3 mm.in diameter.
Macronodular (irregular) cirrhosis, nodules up to one cm in diameter.
Mixed cirrhosis is the end stage of all types of cirrhosis
Microscopic picture
1 Regenerating nodulesn- Proliferated hepatocytes arranged in thick plates and separated by blood sinusoids. Central vein in abnormal sites (eccentric) - Hepatocytes may be small , large , or binucleated
2- Fibrosis- It replaces damaged hepatocytes. It develops at certain sites:-
a-perivenular b -perisinusoidal c -pericellular and d -in relation to portal tracts.
- It may be young, cellular and highly vascular or mature with diminished vasculsarity. It encloses groups of hepatocytes, lobules or regenerating nodules.
-As a result of hepatocyte injury and fibrosis, there’s loss of normal liver architecture including the lobular and acinar pattern as well as the liver cell plates
3- Bile ductular proliferation:- Occurs in the fibrous septa.Focal choestaisis with feathery degeneration of hepatocytes occur at the margins of regenerating nodules. It becomes diffuse terminally.
4- Inflammatory cells:- Lymphocytes, macrophages and plasma cells infiltrate the fibrous septa and regenerating nodules
Etiological classification of cirrhosis
Congenital Occurs at childhood
- congenital syphilis
Hereditary diseases:-
a. Primary idiopathic haemochromatosis b. Thalassemia c. Wilson’s disease d.α 1-antitrypsin deficien e. glycogen storage disease
Acquired
-Cryptogenic (10-50%).
-Alcoholic (30-70%)
-Post viral (15-20%)
- Biliary cirrhosis (16%) primary or secondary.
Psoriasis is a chronic disorder characterized by scaly, erythematous plaques, which histologically are secondary to epidermal proliferation.
- genetic factors (HLA relationships), environmental (physical injury, infection, drugs, photosensitivity), abnormal cellular proliferation (deregulation of epidermal proliferation) and microcirculatory changes in the papillary dermis (diapedesis of neutrophils into the epidermis) are all interrelated.
- the plaques of psoriasis are characteristically well-demarcated pink or salmon colored lesions covered by a loosely-adherent silver-white scale which, when picked off, reveals pinpoint bleeding sites (Auspitz sign).
- the nail changes in psoriasis include pitting, dimpling, thickening and crumbling with a yellowish-brown discoloration of the nail plate.
- the characteristic histologic features of psoriasis include:
- hyperkeratosis
- absence of the granulosa cells (present in lichen planus).
- parakeratosis
- regular, club-shaped elongation of the rete pegs (irregular and saw toothed in lichen planus) with vessel proliferation in the papillary dermis (reason for the bleeding associated with Auspitz sign).
- characteristic subcorneal collection of neutrophils called a Munro's microabscess (diapedesis from vessels in papillary dermi).
- 7% develop HLA B27 positive psoriatic arthritis
Respiratory Pathology
A. Pulmonary infections
1. Bacterial pneumonia
a. Is an inflammatory process of infectious origin affecting the pulmonary parenchyma.
2. Bacterial infections include:
a. Streptococcus pneumoniae (most common).
b. Staphylococcus aureus.
c. Haemophilus influenzae.
d. Klebsiella pneumoniae.
e. Anaerobic bacteria from the mouth
(aspiration of oral secretions).
3. Viral infections include:
a. Influenza.
b. Parainfluenza.
c. Adenoviruses.
d. Respiratory syncytial virus.
Note: viruses can also cause pneumonia. Infection of the interstitial tissues, or interstitial pneumonia, is commonly associated with these types of infections.
Common symptoms include fever, dyspnea, and a productive cough
Two types:
(1) Lobar pneumonia
(a) Infection may spread through entire lobe(s) of lung. Intraalveolar exudates result in dense consolidations.
(b) Typical of S. pneumoniae infections.
(2) Bronchopneumonia
(a) Infection and inflammation spread through distal airways, extending from the bronchioles and alveoli. A patch distribution involving one or more lobes is observed.
(b) Typical of S. aureus, H. influenzae,and K.pneumoniae infection
Diseases that Produce a Productive Cough
Pneumonia
Lung abscess
Tuberculosis
Chronic bronchitis
Bronchiectasis
Bronchogenic carcinoma
Classification
Diseases of the respiratory system can be classified into four general areas:
- Obstructive Diseases (e.g., Emphysema, Bronchitis, Asthma)
- Restrictive Diseases (e.g., Fibrosis, Sarcoidosis, Alveolar Damage, Pleural Effusion)
- Vascular Diseases (e.g., Pulmonary Edema, Pulmonary Embolism, Pulmonary Hypertension)
- Infectious, Environmental and Other Diseases (e.g., Pneumonia, Tuberculosis, Asbestosis, Particulate Pollutants)
FUNGAL INFECTION
Mucormycosis (Zygomycosis; Phycomycosis)
Infection with tissue invasion by broad, nonseptate, irregularly shaped hyphae of diverse fungal species, including Rhizopus, Rhizomucor, Absidia, and Basidiobolus.
Infection is most common in immunosuppressed persons, in patients with poorly controlled diabetes, and in patients receiving the iron-chelating drug desferrioxamine.
Symptoms and Signs
Rhinocerebral mucormycosis is the most common form, but primary cutaneous, pulmonary, or GI lesions sometimes develop, and hematogenous dissemination to other sites can occur. Rhinocerebral infections are usually fulminant and frequently fatal. Necrotic lesions usually appear on the nasal mucosa or sometimes the palate.