Hyperthyroidism 

Hyperthyroidism (Thyrotoxicosis) is a hypermetabolic state caused by elevated circulating levels of free T3 and T4 . This may primary (Graves disease) or rarely, secondary (due to pituitary or hypothalamic diseases).

- The diagnosis is based on clinical features and laboratory data. 

Lab Test

- The measurement of serum TSH concentration provides the most useful single screening test for hyperthyroidism, because TSH levels are decreased in primary cases, even when the disease is still be subclinical. 
- In secondary cases TSH levels are either normal or raised. 
- A low TSH value is usually associated with increased levels of free T4 . 
- Occasionally, hyperthyroidism results from increased levels of T3 .

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.
 

Bacterial endocarditis 
Endocarditis is an infection of the endocardium of the heart, most often affecting the heart valves.

A. Acute endocarditis
1. Most commonly caused by Staphylococcus aureus.
2. It occurs most frequently in intravenous drug users, where it usually affects the tricuspid valve. 

B. Subacute endocarditis

1. Most commonly caused by less virulent organisms, such as intraoral Streptococcus viridans that can be introduced systemically via dental procedures.
2. Pathogenesis: occurs when a thrombus or vegetation forms on a previously damaged or congenitally abnormal valve. These vegetations contain bacteria and inflammatory cells. Complications can arise if the thrombus embolizes, causing septic infarcts.
Other complications include valvular dysfunction or abscess formation.
3. Symptoms can remain hidden for months.
4. Valves affected (listed most to least common):
a. Mitral valve (most frequent).
b. Aortic valve.
c. Tricuspid (except in IV drug users, where the tricuspid valve is most often affected).

The Specific Immune Response

Definition

The immune response comprises all the phenomenon resulting from specific interaction of cells of the immune-system with antigen. As a consequence of this interaction cells  appear that mediate cellular immune response as well cells that synthesis and secrete immunoglobulins

Hence the immune response has 2 components.

1. Cell mediated immunity (CMI).

2:. Humoral immunity (antibodies)

(I) Macrophages. Constituent of the M. P. S. These engulf the antigenic material.

(i) Most of the engulfed antigen is destroyed to' prevent a high dose paralysis of the Immune competent cells.

(ii) Some of it persists in the macrophage, retaining immunogenecity for continued stimulus to the immune system.

(iii)The antigenic information is passed on to  effectors cells. There are two proposed mechanisms for this:

(a) As messenger RNA with code for the specific antibody.

(b) As antigen-RNA complexes.

(2) Lymphocytes. There are 2 main classes recognized by surface characteristics.

(A) T-Lymyhocytes (thymus dependant) :- These are responsible for cellular immunity . On exposure to antigen 

• They transform to immunoblasts  which divide to form the effectors cells.
• They secrete lymphokines These are
  • Monocyte migration inhibition factor
  • Macrophage activation factor
  • Chemotactic factor
  • Mitogenic factor
  • Transfer factor
  • Lymphotoxin which kills target cell
  • Interferon.
  • Inflammatory factor which increases permeability. .
• Some remain as 1onglived memory cell for a  quicker recognition on re-exposure
• They also modify immune response by other lymphocytes in the form of “T – helper cells “ and “T-suppressor” cells
• They are responsible for graft rejection

(B) B-Lymphocytes (Bursa dependent). In birds the Bursa of Fabricious controls

these cells. In man, its role is taken up by," gut associated lymphoid tissue)

(i) They are responsible for antibody synthesis. On stimulation they undergo blastic transformation and then differentiation to plasma cells, the site of immunoglobulin synthesis.

(ii) They also form memory cells. But these are probably short lived.

(C) In addition to T & B lymphocytes, there are some lymphocytes without the surface markers of either of them. These are 'null' cells-the-natural Killer (N,K.) cells and cells responsible for antibody dependent cellular-cytotoxicity.

(3) Plasma cells. These are the effectors cells of humoral immunity. They produce the immunoglobins, which are the effector molecules.

Acanthosis nigricans is a pigmented skin lesion commonly present in the axilla which is a phenotypic marker for an insulin-receptor abnormality as well as a marker for adenocarcinoma, most commonly of gastric origin.

Muscle pathology
1. Myasthenia gravis
a. An autoimmune disease caused by autoantibodies to acetylcholine receptors at the neuromuscular junctions.
b. Characterized by muscle weakness or the inability to maintain long durations of muscle contractions; this worsens during exercise but recovers after rest.
c. Affects various muscle groups, including:
(1) Eyes—diplopia, ptosis.
(2) Neck—dysphagia, problems swallowing or speaking.
(3) Extremities—arms and legs.
d. Treatment: cholinesterase inhibitors(neostigmine), anti-immune therapy.

2. Muscle tumors
a. Rhabdomyoma—benign tumor of skeletal muscle.
b. Leiomyoma
(1) Benign tumor of smooth muscle.
(2) Most common tumor found in women.
(3) Usually affects the uterus, although it can occur anywhere.
c. Rhabdomyosarcoma
(1) Malignant tumor of skeletal muscle.
(2) Most common sarcoma found in children.
(3) Usually affects head and neck region—orbit, nasal cavity, and nasopharynx.