NEET MDS Lessons
General Pathology
Blood-Lymphatic Pathology
Disorders of primary hemostasis
1. General characteristics of disorders of primary hemostasis (due to problems of blood vessels or platelets):
a. Occur early in life.
b. Unlike secondary hemostasis, bleeding occurs in more superficial areas such as skin and mucous membranes rather than in secondary hemostasis.
c. Signs include petechiae.
d. Can be caused by vascular and platelet abnormalities or alterations in the plasma proteins required for adhesion of platelets to vascular subendothelium.
e. Laboratory findings include prolonged bleeding time, as seen in platelet disorders.
2. Vascular abnormalities
Scurvy
(1) Caused by a vitamin C deficiency leading to decreased synthesis of collagen. Note: vitamin C is necessary for the formation of collagen via hydroxylation of lysine and proline.
(2) Symptoms include:
- Delayed wound healing.
- Petechiae and ecchymosis.
- Gingival bleeding, swelling, and ulcerations.
3. Platelet abnormalities
a. Thrombocytopenia
(1) Characterized by a decreased number of platelets.
(2) The most common type of bleeding disorder.
(3) Can be caused by a number of diseases, such as irradiation, acute leukemia, disseminated intravascular coagulation (DIC), or idiopathic thrombocytopenic purpura (ITP).
b. Thrombocytopenic purpura
(1) Idiopathic: An autoimmune disease characterized by the presence of autoantibodies against platelets, resulting in the removal of platelets by splenic macrophages.
(2) May also be drug-induced.
Disorders of secondary hemostasis
1. General characteristics of disorders of secondary hemostasis (due to problems with clotting factors):
a. Symptoms occur later in life.
b. As compared to disorders of primary hemostasis, bleeding occurs in deeper areas and larger vessels (i.e., joint spaces).
c. Laboratory findings include abnormal:
- Partial thromboplastin time (PTT)—measures the intrinsic and common clotting pathway (i.e., tests all coagulation factors except factor 7).
- Prothrombin time (PT)—measures the extrinsic pathway.
- Does not affect the bleeding time.
Hemophilia
a. Caused by a deficiency of particular clotting factor(s).
b. All types of hemophilia affect the intrinsic pathway of the clotting cascade.
c. Signs and symptoms include:
- Prolonged PTT.
- Continuous bleeding from cuts or trauma, which can lead to excessive blood loss.
- Bleeding into joint cavities (hemarthroses) and muscle.
Two types:
(1) Hemophilia A (classic hemophilia)
- Caused by a deficiency of factor 8 (antihemophilic factor).
- Transmission: sex-linked recessive—only occurs in males; however, females can be carriers.
(2) Hemophilia B (Christmas disease)
- Caused by a deficiency of factor 9 (plasma thromboplastin).
- Transmission: sex-linked recessive—only occurs in males; however, females can be carriers.
- Lower incidence rate than hemophilia A.
(3). Vitamin K deficiency
- Causes include malnutrition and malabsorption of fats.
- A decrease in clotting factors 2, 7, 9, and 10 and prothrombin is observed.
- Prolonged PT.
Disorders of both primary and secondary hemostasis
1. von Willebrand’s disease
a. Characterized by a defective von Willebrand’s factor (vWF). Defective vWF affects both primary hemostasis by affecting platelet adhesion to
endothelium, and secondary hemostasis, by a defective factor 8.
b. Genetic transmission: autosomal dominant.
It is the most common hereditary bleeding disorder.
2. Liver disease—disease of the liver results in a decreased production of coagulation factors and therefore can lead to problems with hemostasis.
3. Disseminated intravascular coagulation a condition in which clots form throughout the vasculature. This uses up all available clotting factors and platelets, resulting in problems with bleeding.
Paroxysmal nocturnal haemoglobinuria (PNH).
Feature:
- Acquired RBC rnembrane defect rendering it susceptible to complement lysis.
- Features of intravascular haemolysis.
- Blood picture of haemolysis anemais with pancytopenia.
- Ham’s acid serum test (lysis at 37COin acid pH) + ve
G-6 PD Deficiency
Occurs in Negroes, Mediterranean races, India and far East. It confers a protection Against falciparum malaria.
It is transmitted as X-linked trait of intermediate dominance (variable effect in homozygous females).
Haemolysis may be induced by :
• Primaquin and other anti malarials.
• Other drugs like chloramphenicol , analgesics, antitubercular drugs etc.
• Infections.
• Ingestion of Vicia faba bean (favism).
• Diabetic acidosis
Peutz-Jeghers syndrome
1. Lesions appear as small, melanotic, and freckle-like. They can be found on the skin, oral mucosa, lips, feet, and hands.
2. May also present with intestinal polyps, which may develop into a gastrointestinal carcinoma.
3. Genetic transmission: autosomal dominant.
Erythema multiforme is a hypersensitivity reaction to an infection (Mycoplasma), drugs or various autoimmune diseases.
- probable immunologic disease
- lesions vary from erythematous macules, papules, or vesicles.
- papular lesions frequently look like a target with a pale central area.
- extensive erythema multiforme in children is called Stevens-Johnson syndrome, where there is extensive skin and mucous membrane involvement with fever and respiratory symptoms.
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.
PRIMARY LYMPHEDEMA
can occur as:
1- A congenital defect, resulting from lymphatic agenesis or hypoplasia.
2- Secondary or obstructive lymphedema
- blockage of a previously normal lymphatic; e.g. Malignant tumors
- Surgical procedures that remove lymph nodes
- Postirradiation
- Fibrosis
- Filariasis
- Postinflammatory thrombosis and scarring