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.
 

Monocytosis:
Causes

-Infections causing lymphocytosis, especialy tuberculosis and typhoid. 
-Monocytic leukaemia.
-Some auto immune diseases.

DEGENERATION

Definition:   Reversible cell injury.

(1) Water accumulation in the form   of 

(i)          Cloudy   swelling.

(ii)         Vacuolar   degeneration.

.(ill)        Hydropic   degeneration.

This change  is commonly   seen  in parenchymal   cells  e.g.  kidneys.

Gross appearance: The organ is swollen, soft and pale.

Microscopic appearance: Cells show varying degrees of swelling. Cytoplasm may be granular, vacuolated, homogenously pale and ballooned out.     

(2)  Fatty   change An excessive,   demonstrable accumulation of fat  is common   in  parenchymal cells of liver  and heart

In the liver, it can be due to:   .

(i) Excess  fat  entry  into  the  liver  as occurs  in  starvation  and  in  steroid excess due to mobilization from stores.

(ii) Excess triglyceride formation

(iii) Reduced phosphorlyation  of fat.  

(iv) Decreased release as lipoprotein due to protein deficiency.

Causes

(i) Hypoxia  as  in severe  anaemia  and  venous  stasis

(ii) Protein  malnutrition.

(iii) Hepatotoxins like CCl₄.

(iv) Alcoholism

(v) Metabolic defects like Diabetes mellitus

(vi) Infections.

Gross appearance: The organ is enlarged, soft and greasy, with a pale yellowish colour. It may involve the organ uniformly or patchily ( thrush breast or tabby cat heart)

Microscopic appearance: The cells contain clear vacuoles (stainable by fat-sudan  stains on frozen sections). These may be small and dispersed or large, displacing the nucleus peripherally. Several such cells may fuse to form fat cysts.

(3) Hyaline degeneration

In alcoholic liver damage, the cytoplasmic organelles are damaged and give the cytoplasm a deep eosinophilic staining-Mallory hyaline.

Str. Pneumoniae

Probably the most important streptococci.  Primary cause of pneumonia.  Usually are diplococci.  Ste. pneumoniae are α-hemolytic and nutritionally fastidious.  Often are normal flora.

Key virulence factor is the capsule polysaccharide which prevents phagocytosis.  Other virulence factors include pneumococcal surface protein and α-hemolysin.

Major disease is pneumonia, usually following a viral respiratory infection.  Characterized by fever, cough, purulent sputum.  Bacteria infiltrates alveoli.  PMN’s fill alveoli, but don’t  cause necrosis. Also can cause meningitis, otitis, sinusitis.

There are vaccines against the capsule polysaccharide.  Resistance to penicillin, cephalosporins, erythromycins, and fluoroquinalones is increasing.

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.

Lupus erythematosus
 - chronic discoid lupus is primarily limited to the skin, while SLE can involve the skin and other systems.
 - pathogenesis: light and other external agents plus deposition of DNA (planted antigen) and immune complexes in the basement membrane.
 Histology:
 - basal cells along the dermal-epidermal junction and hair shafts (reason for alopecia) are vacuolated (liquefactive degeneration)
 - thickening of lamina densa as a reaction to injury.
 - immunofluorescent studies reveal a band of immunofluorescence (band test) in involved skin of chronic discoid lupus or involved/uninvolved skin of SLE.
 - lymphocytic infiltrate at the dermal-epidermal junction and papillary dermis.