NEET MDS Lessons
General Pathology
AMYLOIDOSIS
Definition. Extra cellular deposition of an eosinophilic hyaline homogenous material in Various organs, occurring in a variety of clinical states.
Staining reactions
Iodine :- Brown, turning blue on addition of H2SO4 (gross and microscopic Stain).
P.A.S. – Positive (Magenta pink).
Congo Red -Orange red which on polarisation gives green birefringence.
Von Geison's –Khaki colour.
Thioflavin T -Yellow fluorescence.
Amyloid is called typical if it given the above staining reactions Other wise it is termed atypical or para-amyloid.
Classification
1. Systemic amyloidosis associated with underlying disease (secondary),
(A) Chronic infections like
- Tuberculosis.
- Bronchiectasis.
- Lung abscess.
- Osteomyelitis.
- Syphilis.
(B) Chronic inflammations of varied etiology:
- Rheumatoid arthritis.
- Ulcerative colitis.
- Regional enteritis.
- Lupus erythematosus.
(C) Neoplastic proliferations:
- Of immune system – Multiple myeloma, Hodgkin’s disease.
- Cancers like Renal cell carcinoma etc.
II Systemic primary amyloidosis with no underlying cause.
III Heredofamilial types.
- Amyloidosis with mediterranean fever.
- Amyloid polyneuropathy.
- Amyloid nephrophathy
- Familial cardiac amyloidosis
- Familial cutaneous amyloid.
- Lattice corneal dystrophy
IV. Localised amyloidosis:
- Senile - in heart, brain, seminal vesicles.
- Amyloidoma of tongue, bronchial tree, skin.
- In islets of Langerhans in Diabetes mellitus.
- In medullary thyroid carcinoma.
Deposition sites
In relation to reticulin and collagen fibres and to basement, membranes especially
subendothelial.
Organs involved commonly are :
Secondary amyloidosis
- Liver.
- Spleen.
- Kidney
- Lymph nodes.
- Adrenals.
Primary amyloidosis
- Heart
- Tongue and gingiva.
- Gastro intestinal tract.
- Lung.
- Wall of small vessels.
Nature and pathogenesis of amyloid
It is primarily made up of protein arranged in two patterns
- There are filaments twisted together to from the fibrils. These chemically resemble light chains of immunoglobulins
- Rods composed of stacked rings. These are made up of alpha globulin components of plasma proteins (P-components)
- In addition to these, extracts of crude amyloid contain mucopolysacharides complement and gamma globulins.
- Origin of amyloid :- current concept is that it is a direct product of cells of the immune sustem with some abnormality in their immune response
The abnormality may be due to :
- A genetic enzyme defect.
- Prolonged antigenic challenge.
- Neoplastic transformation
- Supression of normal. Response as in induced tolerance.
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).
ATROPHY
It is the acquired decrease in the size of an organ due to decrease in the size and/or number of its constituent cells.
Causes:
(1) Physiological
- Foetal involution.
o Branchial clefts.
o Ductus arterious.
- Involution of thymus and other lymphoid organs in childhood and adolescence.
- In adults:
o Post-partum uterus.
o Post-menopausal ovaries and uterus
o Post-lactational breast
o Thymus.
(2) Pathological:
- Generalised as in
o Ageing.
o Severe starvation and cachexia
- Localised :
o Disuse atropy of bone and muscle.
o Ischaemic atrophy as in arteriosclerotic kidney. .
o Pressure atrophy due to tumours and of kidney in hydronephrosis.
o Lack of trophic stimulus to endocrines and gonads.
Multiple sclerosis
a. A demyelinating disease that primarily affects myelin (i.e. white matter). This affects the conduction of electrical impulses along the axons of nerves. Areas of demyelination are known as plaques.
b. The most common demyelinating disease.
c. Onset of disease usually occurs between ages 20 and 50; slightly more common in women.
d. Disease can affect any neuron in the central nervous system, including the brainstem and spinal cord. The optic nerve (vision) is commonly affected.
Keloids
1. Characterized by a progressively enlarging scar.
2. Caused by an abnormal accumulation of collagen at the site of injury.
3. More common in African-Americans.
Abnormalities in chromosome number
Trisomy 21 (Down syndrome)
(1) The most common chromosomal disorder.
(2) A disorder affecting autosomes. It is generally caused by meiotic nondisjunction in the mother, which results in an extra copy of chromosome 21 or trisomy 21.
(3) Risk increases with maternal age.
(4) Clinical findings include mental retardation and congenital heart defects. There is also an increased risk of developing acute leukemia
and an increased susceptibility to severe infections.
(5) Oral findings include macroglossia, delayed eruption of teeth, and hypodontia.
Trisomies 18 and 13
(1) Trisomy 18 (Edwards syndrome):
characterized by an extra copy of chromosome 18. Oral findings include micrognathia.
(2) Trisomy 13 (Patau’s syndrome): characterized by an extra copy of chromosome 13. Oral findings include cleft lip and palate.
(3) Meiotic nondisjunction is usually the cause of an extra chromosome in both of these trisomies.
(4) Clinical findings for both of these trisomies are usually more severe than trisomy 21. Most children with these diseases die within months after being born due to manifestations such as congenital heart disease.
Klinefelter’s syndrome
(1) One of the most common causes of male hypogonadism.
(2) Characterized by two or more X chromosomes and one or more Y chromosomes. Typically, there are 47 chromosomes with the karyotype of XXY.
(3) The cause is usually from meiotic nondisjunction.
(4) Clinical findings include atrophic and underdeveloped testes, gynecomastia, tall stature, and a lower IQ.
Turner’s syndrome
(1) One of the most important causes of amenorrhea.
(2) Characterized by having only one X chromosome, with a total of 45 chromosomes and a karyotype of XO.
(3) Clinical findings include underdeveloped female genitalia, short stature, webbed neck, and amenorrhea. Affected females are usually
sterile. Unlike other chromosomal disorders, this one is usually not complicated by mental retardation.
Treacher Collins syndrome (mandibulofacial dysostosis)
(1) Genetic transmission: autosomal dominant.
(2) A relatively rare disease that results from abnormal development of derivatives from the first and second branchial arches.
(3) Clinical findings include underdeveloped zygomas and mandible and deformed ears. Oral findings include cleft palate and small or absent parotid glands.
Blastomycosis (North American Blastomycosis; Gilchrist's Disease)
A disease caused by inhalation of mold conidia (spores) of Blastomyces dermatitidis, which convert to yeasts and invade the lungs, occasionally spreading hematogenously to the skin or focal sites in other tissues.
Pulmonary blastomycosis tends to occur as individual cases of progressive infection
Symptoms are nonspecific and may include a productive or dry hacking cough, chest pain, dyspnea, fever, chills, and drenching sweats. Pleural effusion occurs occasionally. Some patients have rapidly progressive infections, and adult respiratory distress syndrome may develop.