Immunodeficiency

This may be :-

• Congenital (Primary)
• Acquired (Secondary)

Features : Complete or near complete lack of T & B lymphoid tissue. Fatal early in life Even with marrow grafting, chances of graft versus host reaction is high.

B. T Cell Defects :

• Thymic dysplasia
• Digeorge’s syndrome
• Nazelof’s syndrome
• Ataxia teltngiectaisa
• Wiscott Aldrich’s syndrome

These  lessons show predominantly defective cell mediated immunity. But they may also show partial immunoglobulin defects cell mediated immunity. But they may also show partial immunoglobulin defects due to absence og T-B co-operation.

C. Humoral immunity defects.

Bruron type- aggammaglobulinaemia.

• Dysgammaglobulinaemias-variable immunodeficiency’s of one or more classes.

Acquired deficiency

A. Immuno suppression by :

• Irradiation.
• Corticoids.
• Anti metabolites.
• Anti lymphocyte serum.

B. Neaplasia  of lymphoid system :

• Hodgkin's and Non Hodgkin's lymphomas.
• Chronic lymphocytic leukaemia..
• Multime myeloma and other paraproteinaemias (normal immunoglobulins reduced in spite of hyperglobulinaemia).

c. excessive protein loss.

• Nephrotic Syndrome.
• Protein losing enteropathy.

Joint pathology
1. Rheumatoid arthritis
a. Cause is autoimmune in nature.
b. More common in women aged 20 to 50.
c. Characterized by inflammation of the synovial membrane. Granulation tissue, known as pannus, will form in the synovium and expand over the articular cartilage. This causes the destruction of the underlying cartilage and results in fibrotic changes and ankylosis.
Scarring, contracture, and deformity of the joints may occur.
d. Clinical symptoms include swollen joints. It can affect any joint in the body.

2. Osteoarthritis
a. Most common arthritis.
b. Cause is unknown.
c. Higher incidence in women, usually after age 50.
d. Characterized by degeneration of the articular cartilage and the formation of osteophytes (bony spurs) at the margins of affected areas.
Clinical signs and symptoms include:
(1) Stiff and painful joints affecting joints in the hand (phalangeal joints) and weight-bearing joints.
(2) Heberden’s nodes—nodules at the distal interphalangeal joint.
(3) Bocard’s nodes—nodules at the proximal interphalangeal joint.

Post viral (post hepatitic) cirrhosis (15-20%) 

Cause:- Viral hepatitis (mostly HBV or HCV) 
Acute hepatitis  → chronic hepatitis → cirrhosis.  

Pathology
Liver is shrunken.  Fatty change is absent (except with HCV). Cirrhosis is mixed.

M/E  :-
Hepatocytes-show degeneration, necrosis  as other types of cirrhosis. 
Fibrous septa   -They are thick and immature (more cellular and vascular).
- Irregular margins (piece meal necrosis).
- Heavy lymphocytic infiltrate.

Prognosis:- - More rapid course than alcoholic cirrhosis.Hepatocellular carcinoma is more liable to occur 
 

HAEMORRHAGIC DISORDERS

Normal homeostasis depends on

 -Capillary integrity and tissue support.

- Platelets; number and function

(a) For integrity of capillary endothelium and platelet plug by adhesion and aggregation

(b) Vasoactive substances for vasoconstriction

(c) Platelet factor for coagulation.

(d) clot retraction.

- Fibrinolytic system(mainly Plasmin) : which keeps the coagulation system in check.

Coagulation disorders

These may be factors :

Deficiency .of factors

• Genetic.
• Vitamin K deficiency.
• Liver disease.
• Secondary to disseminated intravascular coagulation.or defibrinatian

Overactive fibrinolytic system.

Inhibitors of  the factors (immune, acquired).

Anticoagulant therapy as in myocardial infarction.

Haemophilia. Genetic disease transmitted as X linked recessive trait. Common in Europe. Defect in fcatorVII   Haemophilia A .or in fact .or IX-Haemaphilia B (rarer).

Features:

• May manifest in infancy or later.
• Severity depends  on degree of deficiency.
• Persistant wound bleeding.
• Easy Bruising with Hematoma formation

Nose bleed , arthrosis, abdominal pain with fever and leukocytosis

Prognosis is good with prevention of trauma and-transfusion of Fresh blood or fTesh plasma except for danger of developing immune inhibitors.

Von Willebrand's disease. Capillary fragility and decreased factor VIII (due to deficient stimulatory factor). It is transmitted in an autosomal dominant manner both. Sexes affected equally

Vitamin K  Deficiency. Vitamin K is needed for synthesis of factor II,VII,IX and X.

Deficiency maybe due to:

Obstructive jaundice.

Steatorrhoea.

Gut sterilisation by antibiotics.

Liver disease results in :

Deficient synthesis of factor I II, V, Vll, IX and X  Incseased fibrinolysis (as liver is the site of detoxification of activators ).

Defibrination syndrome. occurs when factors are depleted due to disseminated .intravascular coagulation (DIC). It is initiated by endothelial damage or tissue factor entering the circulation.

Causes

Obstetric accidents, especially amniotic fluid embolism. Septicaemia. .

Hypersensitivity reactions.

Disseminated malignancy.

Snake bite.

Vascular defects : (Non thrombocytopenic purpura).

Acquired :

Simple purpura a seen in women. It is probably endocrinal

Senile parpura in old people due to reduced tissue support to vessels

Allergic or toxic damage to endothelium due to  Infections like Typhoid Septicemia

Col!agen diseases.

Scurvy

Uraemia damage to  endothelium (platelet defects).

Drugs like aspirin. tranquillisers, Streptomvcin pencillin etc.

Henoc schonlien purpura Widespeard vasculitis due to hypersensitivity to bacteria or foodstuff

It manifests as :

Pulrpurric rashes.

Arthralgia.

Abdominal pain.

Nephritis and haematuria.

Hereditary :

(a) Haemhoragic telangieclasia. Spider like tortous vessels which bleed easily. There are disseminated lesions in skin, mucosa and viscera.

(b) Hereditary capillary fragilily similar to the vascular component of von Willbrand’s disease

.(c) Ehler Danlos Syndrome which is a connective tissue defect with skin, vascular and joint manifestations.

Platelet defects

These may be :

(I) Qualitative thromboasthenia and thrombocytopathy.

(2) Thrombocytopenia :Reduction in number.

(a) Primary or idiopathic thrombocytopenic purpura.

(b) Secondary to :

(i) Drugs especially sedormid

(ii) Leukaemias

(iii) Aplastic-anaemia.

Idiopathic thrombocytopenic purpura (ITP). Commoner in young females.

Manifests as :

Acute self limiting type.

Chronic recurring type.

Features:

(i) Spontaneous bleeding and easy bruisability

(ii)Skin (petechiae), mucus membrane (epistaxis) lesions and sometimes visceral lesions involving any organ.

Thrombocytopenia with abnormal forms of platelets.

Marrow shows increased megakaryocytes with immature forms, vacuolation, and lack of platelet budding.

Pathogenesis:

hypersensitivity to infective agent in acute type.

Plasma thrombocytopenic factor ( Antibody in nature) in chronic type

Fibrous and Fibro-Osseous Tumors

Fibrous tumors of bone are common and comprise several morphological variants.
1. Fibrous Cortical Defect and Nonossifying Fibroma 
Fibrous cortical defects occur in 30% to 50% of all children older than 2 years of age; they are probably developmental rather than true neoplasms. The vast majority are smaller than 0.5 cm and arise in the metaphysis of the distal femur or proximal tibia; almost half are bilateral or multiple. They may enlarge in size (5-6 cm) to form nonossifying fibromas. Both lesions present as sharply demarcated radiolucencies surrounded by a thin zone of sclerosis. Microscopically are cellular and composed of benign fibroblasts and macrophages, including multinucleated forms. The fibroblasts classically exhibit a storiform pattern. Fibrous cortical defects are asymptomatic and are usually only detected as incidental radiographic lesions. Most undergo spontaneous differentiation into normal cortical bone. The few that enlarge into nonossifying fibromas can present with pathologic fracture; in such cases biopsy is necessary to rule out other tumors.

2. Fibrous Dysplasia 

is a benign mass lesion in which all components of normal bone are present, but they fail to differentiate into mature structures. Fibrous dysplasia occurs as one of three clinical patterns:
A. Involvement of a single bone (monostotic)
B. nvolvement of multiple bones (polyostotic)
C. Polyostotic disease, associated with café au lait skin pigmentations and endocrine abnormalities, especially precocious puberty (Albright syndrome).

Monostotic fibrous dysplasia accounts for 70% of cases. It usually begins in early adolescence, and ceases with epiphyseal closure. It frequently involves ribs, femur, tibia & jawbones. Lesions are asymptomatic and usually discovered incidentally. However, fibrous dysplasia can cause marked enlargement and distortion of bone, so that if the face or skull is involved, disfigurement can occur.

Polyostotic fibrous dysplasia without endocrine dysfunction accounts for the majority of the remaining cases. 
It tends to involve the shoulder and pelvic girdles, resulting in severe deformities and spontaneous fractures.

Albright syndrome accounts for 3% of all cases. The bone lesions are often unilateral, and the skin pigmentation is usually limited to the same side of the body. The cutaneous macules are classically large, dark to light brown (café au lait), and irregular.

Gross features

• The lesion is well-circumscribed, intramedullary; large masses expand and distort the bone.
On section it is tan-white and gritty.

Microscopic features

• There are curved trabeculae of woven bone (mimicking Chinese characters), without osteoblastic rimming
• The above are set within fibroblastic proliferation
Individuals with monostotic disease usually have minimal symptoms. By x-ray, lesions exhibit a characteristic ground-glass appearance with well-defined margins. Polyostotic involvement is frequently associated with progressive disease, and more severe skeletal complications (e.g., fractures, long bone deformities, and craniofacial distortion). Rarely, polyostotic disease can transform into osteosarcoma, especially following radiotherapy. 

Immunodeficiency

This may be :- 
- Congenital (Primary)
- Acquired (Secondary)

Features : Complete or near complete lack of T & B lymphoid tissue. Fatal early in life Even with marrow grafting, chances of graft versus host reaction is high.

T Cell Defects :

- Thymic dysplasia
- Digeorge’s syndrome
- Nazelof’s syndrome
- Ataxia teltngiectaisa
- Wiscott Aldrich’s syndrome

These  lessons show predominantly defective cell mediated immunity. But they may also show partial immunoglobulin defects cell mediated immunity. But they may also show partial immunoglobulin defects due to absence og T-B co-operation.

C. Humoral immunity defects.
Bruron type- aggammaglobulinaemia.
- Dysgammaglobulinaemias-variable immunodeficiency’s of one or more classes.

Acquired deficiency

A. Immuno suppression by :
- Irradiation.
- Corticoids.
- Anti metabolites.
- Anti lymphocyte serum.

B. Neaplasia  of lymphoid system :

- Hodgkin's and Non Hodgkin's lymphomas.
- Chronic lymphocytic leukaemia..
- Multime myeloma and other paraproteinaemias (normal immunoglobulins reduced in spite of hyperglobulinaemia).

c. excessive protein loss.
- Nephrotic Syndrome.
- Protein losing enteropathy.