NEET MDS Lessons
General Pathology
Adrenocortical Hyperfunction (Hyperadrenalism)
Hypercortisolism (Cushing Syndrome) is caused by any condition that produces an elevation in glucocorticoid levels. The causes of this syndrome are
A. Exogenous through administration of exogenous glucocorticoids; the most common causeB. Endogenous
1. Hypothalamic-pituitary diseases causing hypersecretion of ACTH (Cushing disease)
2. Adrenocortical hyperplasia or neoplasia
3. Ectopic ACTH secretion by nonendocrine neoplasms (paraneoplastic)
Pathological features
- The main lesions of Cushing syndrome are found in the pituitary and adrenal glands.
- The most common change in the pituitary, results from high levels of endogenous or exogenous glucocorticoids, is termed Crooke hyaline change. In this condition, the normal granular, basophilic cytoplasm of the ACTH-producing cells in the anterior pituitary is replaced by homogeneous, lightly basophilic material. This is due to accumulation of intermediate keratin filaments in the cytoplasm.
- There is one of four changes in the adrenal glands, which depends on the cause.
1. Cortical atrophy
2. Diffuse hyperplasia
3. Nodular hyperplasia
4. Adenoma, rarely a carcinoma
1. In patients in whom the syndrome results from exogenous glucocorticoids, suppression of endogenous ACTH results in bilateral cortical atrophy, due to a lack of stimulation of the cortex by ACTH. In cases of endogenous hypercortisolism, in contrast, the adrenals either are hyperplastic or contain a cortical neoplasm.
2. In Diffuse hyperplasia the adrenal cortex is diffusely thickened and yellow, as a result of an increase in the size and number of lipid-rich cells in the zonae fasciculata and reticularis.
3. Nodular hyperplasia, which takes the form of bilateral, up to 2.0-cm, yellow nodules scattered throughout the cortex.
4. Primary adrenocortical neoplasms causing Cushing syndrome may be benign or malignant. The adrenocortical adenomas are yellow tumors surrounded by capsules, and most weigh < 30 gm .
Haemolysis due to drugs and chemicals
This can be caused by :
1. Direct toxic action.
-> Naphthalene.
-> Nitrobenzene.
-> Phenacetin.
-> Lead.
Heinz bodies are seen in abundance.
2. Drug action on G-6-PD deficient RBC
3. Immunological mechanism which may be :
-> Drug induced autoantibody haemolysis, Antibodies are directed against RBC.
-> Hapten-cell mechanism where antibodies are directed against which is bound to cell surface e.g. Penicilin.
Haemolytic anaemia
Anemia due to increased red cell destruction (shortened life span)
Causes:
A. Corpuscular defects:
1.Membrane defects:
- Spherocytosis.
- Elliptocytosis.
2. Haemoglobinopathies:
- Sickle cell anaemia.
- Thalassaemia
- Hb-C, HBD, HbE.
3. Enzyme defects .deficiency of:
- GIucose -6 phosphate dehydrogenase (G6-PD)
- Pyruvate kinase
4. Paroxysmal nocturnal haemoglobinuria.
B. Extracorpusular mechanisms
1. Immune based:
- Autoimmune haemolytic anaemia.
- Haemolytic disease of new born.
- Incompatible transfusion.
- Drug induced haemolysis
2. Mechanical haemolytic anaemia.
3. Miscellaneous due to :
- Drugs and chemicals.
- Infections.
- Burns.
features of haemolytic anaemia
- Evidence of increased Hb breakdown:
-> Unconjugated hyperbilirubinaemia.
-> Decreased plasma haptoglobin.
-> Increased urobilinogen and stercobilinogen.
-> Haemoglobinaemia, haemoglobinuria and haemosiderinuria if Intravascular haemolysis occurs.
- Evidence or compensatory erythroid hyperplasia:
-> Reticulocytosis and nucleated RBC in peripheral smear.
-> Polychromasia and macrocytes
-> Marrow erythroid hyperplasia
-> Skull and other bone changes.
- Evidences of damage to RBC:
-> Spherocytes and increased osmotic fragility
-> Shortened life span.
-> Fragmented RBC.
-> Heinz bodies.
Autoimmune(acquired) Haemolytic anaemia
Auto antibodies are usually Ig g type (may be Ig M or Ig A). They may or may not bind complement and may be active in warm or cold temperature They may be complete (agggIutinating) or incomplete. Haemolysis s may be intravascular due to destruction of the antibody coated cells by RE system.
Causes:
a. Idiopathic
b. Secondary to
o Drugs - Methyldopa, Mefanamic acid
o Disease like
-> Infections especially viral.
-> Autoimmune disease especially SLE.
-> Lymphomas and chronic lymphatic leukaemia.
-> Tumours.
Diagnosis : is based on
• Evidences of haemolytic anaemia.
• Demonstration of antibodies
- On red cell surface by direct Coomb’s test
- In serum by indirect Coomb’s test.
Histopathological techniques
Histopathological examination studies tissues under the microscope. During this study, the pathologist looks for abnormal structures in the tissue. Tissues for histopathological examination are obtained by biopsy. Biopsy is a tissue sample from a living person to identify the disease. Biopsy can be either incisional or excisional.
Once the tissue is removed from the patient, it has to be immediately fixed by putting it into adequate amount of 10% Formaldehyde (10% formalin) before sending it to the pathologist.
The purpose of fixation is:
1. to prevent autolysis and bacterial decomposition and putrefaction
2. to coagulate the tissue to prevent loss of easily diffusible substances
3. to fortify the tissue against the deleterious effects of the various stages in the preparation of sections and tissue processing.
4. to leave the tissues in a condition which facilitates differential staining with dyes and other reagents.
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.
EMBOLISM
An embolus is a detached intravascular solid, liquid, or gaseous mass that is carried by the blood to a site distant from its point of origin
99% due to dislodged thrombus
Types:
1. Thrombo-embolism
2. Fat embolism
3. Air embolism
4. Nitrogen embolism
Emboli result in partial or complete vascular occlusion.
The consequences of thromboembolism include ischemic necrosis (infarction) of downstream tissue
PULMONARY THROMBOEMBOLISM
- 95% originate from deep veins of L.L
Special variants: - Saddle embolus: at bifurcation of Pulmonary artery
Paradoxical embolus: Passage of an embolus from venous to systemic circulation through IAD, IVD
CLINICAL CONSEQUENCE OF PULMONARY THROMBOEMBOLISM :
Most pulmonary emboli (60% to 80%) are clinically silent because they are small
a. Organization: 60 – 80 %
b. Sudden death, Right ventricle failure, CV collapse when more than 60 % of pulmonary vessels are obstructed.
c. Pulmonary hemorrhage: obstruction of medium sized arteries.
d. Pulmonary Hypertension and right ventricular failure due to multiple emboli over a long time.
Systemic thromboembolism
Emboli traveling within the arterial circulation
80% due to intracardiac mural thrombi
2/3 Lt. ventricular failure
The major targets are:
1. Lower limbs 75%
2. Brain 10%
3. Intestines
4. Kidneys
5. Spleen
Fat embolism
Causes
1. Skeletal injury (fractures of long bones )
2. Adipose tissue Injury
Mechanical obstruction is exacerbated by free fatty acid release from the fat globules, causing local toxic injury to endothelium. - In skeletal injury, fat embolism occurs in 90% of cases, but only 10% or less have clinical findings
Fat embolism syndrome is characterized by
A. Pulmonary Insufficiency
B. Neurologic symptoms
C. Anemia
D. Thrombocytopenia
E. Death in 10% of the case
Symptoms appears 1-3 days after injury
Tachypnea, Dyspnea, Tachycardia and Neurological symptoms
Air Embolism
causes: 1. Obstetric procedures
2. Chest wall injury
3. Decompression sickness: in Scuba and deep-sea divers ((nitrogen ))
More then 100ml of air is required to produce clinical effect.
Clinical consequence
1. Painful joints: due to rapid formation of gas bubbles within Sk. Muscles and supporting tissues.
2. Focal ischemia in brain and heart
3. Lung edema, Hemorrhage, atelectasis, emphysema, which all lead to Respiratory distress. (chokes)
4. caisson disease: gas emboli in the bones leads to multiple foci of ischemic necrosis, usually the heads of the femurs, tibias, and humeri
Amniotic fluid embolism
- Mortality Rate = 20%-40%
- Very rare complication of labor
- due to infusion of amniotic fluid into maternal circulation via tears in placental membranes and rupture of uterine veins.
- sudden severe dyspnea, cyanosis, and hypotensive shock, followed by seizures, DIC and coma
- Findings: Squamous cells, languo hair, fat, mucin …..etc within the pulmonary microcirculation