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General Pathology

Langerhans cell granulomatosis (histocytosis X)
a. A group of diseases that are caused by the proliferation of Langerhans’ cells (previously known as histocytes).
b. Most commonly causes bone lesions; however, other tissues can be affected.
c. Histologic findings include Langerhans’ cells containing Birbeck granules and eosinophils.

d. Three types:
(1) Letterer-Siwe disease—an acute, disseminated form that is fatal in infants.
(2) Hand-Schüller-Christian disease—a chronic, disseminated form that has a better prognosis than LettererSiwe disease. It usually presents
before the age of 5 and is characterized by a triad of symptoms:
(a) Bone lesions—found in skull, mandible (loose teeth).
(b) Exophthalmos.
(c) Diabetes insipidus.
(3) Eosinophilic granuloma of bone—a localized, least severe form of the three. Lesions may heal without treatment.
(a) Most commonly occurs in young adults.
(b) Lesions in the mandible may cause loose teeth.

Cor pulmonale
a failure of the right side of the heart. It is caused by prolonged high blood pressure in the right ventricle of the heart, which in turn is most often caused by pulmonary hypertension - prolonged high blood pressure in the arteries or veins of the lungs. People with heart disease, or lung diseases such as cystic fibrosis, are at greater risk.

Pathophysiology

There are several mechanisms leading to pulmonary hypertension and cor pulmonale:
Pulmonary vasoconstriction
Anatomic changes in vascularisation
Increased blood viscosity
Primary pulmonary hypertension

Causes

Acute: 
•    Massive pulmonary embolization
•    Exacerbation of chronic cor pulmonale
Chronic: 
•    COPD
•    Loss of lung tissue following trauma or surgery
 

Pneumoconioses—are environmentally related lung diseases that result from chronic inhalation of various substances.

1. Silicosis (stone mason’s disease) 
a. Inhalant: silica dust.
b. Associated with extensive fibrosis of the lungs.
c. Patients have a higher susceptibility to tuberculosis infections.

2. Asbestosis
a. Inhalant: asbestos fibers.
b. Associated with the presence of pleural plaques.
c. Consequences include:
(1) Mesothelioma (malignant mesothelial tumor).
(2) Bronchogenic carcinoma.

3. Anthracosis
a. Inhalant: carbon dust.
b. Usually not as harmful as silicosis or asbestosis.
c. Associated with the presence of macrophages containing carbon.

Hepatitis D virus—can only infect cells previously infected with hepatitis B. 
 Delta hepatitis (HDV) is associated with a 35-nm RNA virus composed of a delta antigen-bearing core surrounded by HBV's Ag coat;

HDV requires HBV for replication.

Delta hepatitis can cause quiescent HBV states to suddenly worsened . Its transmission is the same as that of HBV.
 
 Hepatitis E virus—a high mortality rate in infected pregnant women.

Hepatitis E (HEV) is caused by a single-stranded RNA virus. The disease is typically self-limited and does not evolve into chronic hepatitis; it may, however, be cholestatic.

Pregnant women may develop fulminant disease.

Transmission is by the fecal oral route.

HEV occurs mainly in India, Nepal, Pakistan, and Southeast Asia.
 

IMMUNITY AND RESISTANCE TO INFECTION

Body's resistance to infection depends upon:

I. Defence mechanisms at surfaces and portals of entry.

II. Nonspecific or innate immunity

Ill. Specific immune response.

I.  Surface Defence Mechanisms

1. Skin:

(i) Mechanical barrier of keratin and desquamation.

(ii) Resident commensal organisms

(iii)Acidity of sweat.

(iv) Unsaturated fatty acids of sebum

2. Oropharyngeal

(i)Resident flora

(ii) Saliva, rich in lysozyme, mucin and Immunoglobulins (lgA).

3. Gastrointestinal tract.-

(i) Gastric HCI

(ii) Commensal organisms in Intestine

(iii) Bile salts

(iv) IgA.

(v) Diarrhoeal expulsion of irritants.

4. Respiratory tract:

(i) Trapping in turbinates

(ii) Mucus trapping

(iii) Expulsion by coughing and sneezing.

(iv) Ciliary propulsion.

(V) Lysozymes and antibodies in secretion.

(vi) Phagocytosis by alveolar macrophages.

5. Urinary tract:

(i) Flushing action.

(ii) Acidity

(iii) Phagocytosis by urothelial cells.

6. Vagina.-

(i) Desquamation.

(ii) Acid barrier.

(iii) Doderlein's bacilli (Lactobacilli)

7. Conjunctiva:

Lysozymes and IgA in tears

 

II. Nonspecific or Innate Immunity

1. Genetic factors

  • Species: Guinea pig is very susceptible to tuberculosis.
  • Race: Negroes are more susceptible to tuberculosis than whites
  • Sickle cells (HbS-a genetic determined Haemoglobinopathy resistant to Malarial parasite.

2. Age Extremes of age are more susceptible.

3. Hormonal status. Low resistance in:

  • Diabetes Mellitus.
  • Increased corticosteroid levels.
  • Hypothyroidism

4. Phagocytosis. Infections can Occur in :

  • Qualitative  or quantitative defects in neutrophils and monocytes.
  • Diseases of mononuclear phagocytic system (Reticuloendothelial cells-RES).
  • Overload blockade of RES.

5. Humoral factors

  • Lysozyme.
  • Opsonins.
  • Complement
  • Interferon (antiviral agent secreted by cells infected by virus) 

III. 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.

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).

 

Bacterial meningitis (pyogenic, suppurative infections)

1. Common causes include:
a. Escherichia coli in newborns.
b. Haemophilus influenzae in infants and children.
c. Neisseria meningitides in young adults.
d. Streptococcus pneumoniae and Listeria monocytogenes in older adults.

Clinical findings include severe headache, irritability, fever, and a stiff neck.
a. A spinal tap shows CSF fluid that is cloudy or purulent and is under increased pressure. There is also an increase in protein and a decrease in glucose levels.
3. Can be fatal if left untreated.

 

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