NEET MDS Lessons
General Pathology
Malnutrition
A. Marasmus - calorie malnutrition
A child with marasmus suffers growth retardation and loss of muscle. The loss of muscle mass results from catabolism and depletion of the somatic protein compartment.
With such losses of muscle and subcutaneous fat, the extremities are emaciated; by comparison, the head appears too large for the body. Anemia and manifestations of multivitamin deficiencies are present, and there is evidence of immune deficiency, particularly of T cell-mediated immunity.
B. Kwashiorkor - protein malnutrition - importance of protein quality as well as quantity
Marked protein deprivation is associated with severe loss of the visceral protein compartment, and the resultant hypoalbuminemia gives rise to generalized, or dependent, edema.
The weight of children with severe kwashiorkor is typically 60% to 80% of normal.
However, the true loss of weight is masked by the increased fluid retention (edema).
Children with kwashiorkor have characteristic skin lesions, with alternating zones of hyperpigmentation, areas of desquamation, and hypopigmentation, giving a "flaky paint" appearance.
Hair changes include overall loss of color or alternating bands of pale and darker hair, straightening, line texture, and loss of firm attachment to the scalp.
An enlarged, fatty liver (resulting from reduced synthesis of carrier proteins) and a tendency to develop early apathy, listlessness, and loss of appetite.
The bone marrow in both kwashiorkor and marasmus may be hypoplastic, mainly because of decreased numbers of red cell precursors. How much of this derangement is due to a deficiency of protein and folates or to reduced synthesis of transferrin and ceruloplasmin is uncertain. Thus, anemia is usually present, most often hypochromic microcytic anemia, but a concurrent deficiency of folates may lead to a mixed microcytic-macrocytic anemia.
C. Most cases of severe malnutrition are a combination of A and B usually characterized by:
• Failure of growth
• Behavioral changes
• Edema (kwashiorkor)
• Dermatosis
• Changes in hair
• Loss of appetite
• Liver enlargement
• Anemia
• Osteoporosis
Group A Streptococcus
- scarlet fever usually begins as a Streptococcal pharyngitis/tonsillitis and then develops an erythematous rash beginning on the trunk and limbs with eventual desquamation.
- rash is due to elaboration of erythrogenic toxin by the organism
- face is usually spared, but, if involved there is a characteristic circumoral pallor and the tongue becomes bright red, thus the term "strawberry tongue".
- post-streptococcal immune complex glomerulonephritis is a possible sequela of scarlet fever.
- Dick test is a skin test that evaluates immunity against scarlet fever; no response indicates immunity (anti-toxin antibodies present); erythema indicates no immunity.
- impetigo due to Streptococcus pyogenes is characterized by honey colored, crusted lesions, while those with a predominantly bullous pattern are primarily due to Staphylococcus aureus.
- cellulitis with lymphangitis ("red streaks") is characteristic of Streptococcus pyogenes.
- hyaluronidase is a spreading factor that favors the spread of infection throughout the subcutaneous tissue unlike Staphylococcus aureus which generates coagulase to keep the pus confined.
- erysipelas refers to a raised, erythematous ("brawny edema"), hot cellulitis, usually on the face that commonly produces septicemia, if left untreated.
Osteonecrosis (Avascular Necrosis)
Ischemic necrosis with resultant bone infarction occurs mostly due to fracture or after corticosteroid use. Microscopically, dead bon trabevulae (characterized by empty lacunae) are interspersed with areas of fat necrosis.
The cortex is usually not affected because of collateral blood supply; in subchondral infarcts, the overlying articular cartilage also remains viable because the synovial fluid can provide nutritional support. With time, osteoclasts can resorb many of the necrotic bony trabeculae; any dead bone fragments that remain act as scaffolds for new bone formation, a process called creeping substitution.
Symptoms depend on the size and location of injury. Subchondral infarcts often collapse and can lead to severe osteoarthritis.
ADRENAL INSUFFICIENCY
Adrenocortical hypofunction is either primary (adrenocrtical) or secondary (ACTH deficiency). Primary insufficiency is divided into acute & chronic.
Acute Adrenocortical Insufficiency occurs most commonly in the following clinical settings
- massive adrenal hemorrhage including Waterhouse-Friderichsen syndrome
- Sudden withdrawal of long-term corticosteroid therapy
- Stress in those with chronic adrenal insufficiency
Massive adrenal hemorrhage may destroy the adrenal cortex sufficiently to cause acute adrenocortical
insufficiency. This condition may occur
1. in patients maintained on anticoagulant therapy
2. in postoperative patients who develop DIC
3. during pregnancy
4. in patients suffering from overwhelming sepsis (Waterhouse-Friderichsen syndrome)
Waterhouse-Friderichsen syndrome is a catastrophic syndrome classically associated with Neisseria meningitidis septicemia but can also be caused by other organisms, including Pseudomonas species, pneumococci & Haemophilus influenzae. The pathogenesis of the syndrome remains unclear, but probably involves endotoxin-induced vascular injury with associated DIC.
Chronic adrenocortical insufficiency (Addison disease) results from progressive destruction of the adrenal cortex. More than 90% of all cases are attributable to one of four disorders:
1. autoimmune adrenalitis (the most common cause; 70% of cases)
2. tuberculosis &fungal infections
3. AIDS
4. Metastatic cancers
In such primary diseases, there is hyperpigmentation of the skin oral mucosa due to high levels of MSH (associated with high levels of ACTH).
Autoimmune adrenalitis is due to autoimmune destruction of steroid-producing cells. It is either isolated associated other autoimmune diseases, such as Hashimoto disease, pernicious anemia, etc.
Infections, particularly tuberculous and fungal
Tuberculous adrenalitis, which once was responsible for as many as 90% of cases of Addison disease, has become less common with the advent of antituberculous therapy. When present, tuberculous adrenalitis is usually associated with active infection elsewhere, particularly the lungs and genitourinary tract. Among fungi, disseminated infections caused by Histoplasma capsulatum is the main cause.
AIDS patients are at risk for developing adrenal insufficiency from several infectious (cytomegalovirus, Mycobacterium avium-intracellulare) and noninfectious (Kaposi sarcoma) complications.
Metastatic neoplasms: the adrenals are a fairly common site for metastases in persons with disseminated carcinomas. Although adrenal function is preserved in most such patients, the metastatic growths sometimes destroy sufficient adrenal cortex to produce a degree of adrenal insufficiency. Carcinomas of the lung and breast are the major primary sources.
Secondary Adrenocortical Insufficiency
Any disorder of the hypothalamus and pituitary, such as metastatic cancer, infection, infarction, or irradiation, that reduces the output of ACTH leads to a syndrome of hypoadrenalism having many similarities to Addison disease. In such secondary disease, the hyperpigmentation of primary Addison disease is lacking because melanotropic hormone levels are low.
Secondary adrenocortical insufficiency is characterized by low serum ACTH and a prompt rise in plasma cortisol levels in response to ACTH administration.
Pathological features of adrenocortical deficiency
- The appearance of the adrenal glands varies with the cause of the insufficiency.
- In secondary hypoadrenalism the adrenals are reduced to small, uniform, thin rim of atrophic yellow cortex that surrounds a central, intact medulla. Histologically, there is atrophy of cortical cells with loss of cytoplasmic lipid, particularly in the zonae fasciculata and reticularis.
- In primary autoimmune adrenalitis there is also atrophy of the cortex associated with a variable lymphoid infiltrate that may extend into the subjacent medulla. The medulla is otherwise normal.
- In tuberculosis or fungal diseases there is granulomatous inflammatory reaction. Demonstration of the responsible organism may require the use of special stains.
- With metastatic carcinoma, the adrenals are enlarged and their normal architecture is obscured by the infiltrating neoplasm.
Immunoglobulins. (Ig)
These are made up of polypeptide chains. Each molecule is constituted by two heavy and two light chains, linked by disulfide (S-S) bonds. The h~ chains are of 5 types, with corresponding, types or immunoglobulin. IgG (gamma), IgM (mu µ ), IgA(alpha α), IgD(delta ), IgE(epsilon)
Each of these can have light chains of either kappa (k) or lambda type.Each chain has a constant portion (constant for the subtype) land a variable portion (antigen specific).
Enzyme digestion can split the Ig molecule into.2 Fab (antibody binding) fragments and one Fc (crystallisable, complement binding ) fragment.
STREPTOCOCCAL INFECTIONS
Most streptococci are normal flora of oropharynx
Group A streptococci: Str. pyogenes
Group B streptococci: Str. agalactiae
Str. pneumoniae
Strep viridans group
Group D: Enterococcus (lately Strep. Fecalis and E. fecium), causes urinary tract infections,
Megaloblastic anaemia
Metabolism: B12(cyanocobalamin) is a coenzyme in DNA synthesis and for maintenance of nervous system. Daily requirement 2 micro grams. Absorption in terminal ileum in the presence gastric intrinsic factor. It is stored in liver mainly-
Folic acid (Pteroylglutamic acid) is needed for DNA synthesis.. Daily requirement 100 micro grams. Absorption in duodenum and jejunum
Causes of deficiency .-
- Nutritional deficiency-
- Malabsorption syndrome.
- Pernicious anaemia (B12).
- Gastrectomy (B12).
- Fish tapeworm infestation (B12).
- Pregnancy and puerperium (Folic acid mainly).
- Myeloproliferative disorders (Folic acid).
- Malignancies (Folic acid).
- Drug induced (Folic-acid)
Features:
(i) Megaloblastic anaemia.
(ii) Glossitis.
(iii) Subacute combined degeneration (in B12deficiency).
Blood picture :
- Macrocytic normochromic anaemia.
- Anisocytosis and poikilocytosis with Howell-Jolly bodies and basophilic stippling.
- Occasional megalo blasts may be-seen.
- Neutropenia with hypersegmented neutrophills and macropolycytes.
- Thrombocytopenia.
- Increased MVC and MCH with normal or decreased MCHC.
Bone marrow:
- Megaloblasts are seen. They are larger with a more open stippled chromatin. The nuclear maturation lags behind. the cytoplasmic maturation. Maturation arrest is seen (more of early forms).
- Immature cells of granulocyte series are also larger.
-Giant stab forms (giant metamyelocytes).