Hereditary spherocytosis.

Functionally normal cells which are destroyed .in spleen because of the structural abnormality. It is transmitted as an autosomal dominant trait 

Congenital hemolytic anemia due to genetically determined abnormal spectrin and ankyrin molecules, leading to defects in red blood cell membrane, causing spherical shape and lack of plasticity
Red blood cells become trapped within spleen and have less than usual 120 day lifespan
Splenic function is normal
Osmotic fragility: increased; basis for diagnostic testing 

Description

Firm, deep red tissue, thin capsule, no grossly identifiable malpighian follicles, 100-1000g
Peripheral blood images
Marked congestion in cords
Sinuses appear empty but actually contain ghost red blood cells
May have prominent endothelial lined sinuses, hemosiderin deposition, erythrophagocytosis

Strep viridans

Mixed species, all causing α-hemolysis.  All are protective normal flora which block adherence of other pathogens.  Low virulence, but can cause some diseases:

Sub-acute endocarditis can damage heart valves.

Abscesses can form which are necrotizing.  This is the primary cause of liver abscesses.

Dental caries are caused by Str. mutans.  High virulence due to lactic acid production from glucose fermentation.  This is why eating sugar rots teeth.  Also have surface enzymes which deposit plaque.

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.

Liver cirrhosis

It is a chronic, progressive diffuse process characterized by 
a. Hepatocellular necrosis           
b. Replacement by fibrosis and inflammation 
c. Hyperplasia of surviving liver cells forming regenerating nodules 
d. Vascular derangement. 

All these changes lead to loss of the normal liver architecture. 

Pathology of cirrhosis
At first the liver is enlarged or of normal size. Late in the disease, it is reduced in size and weight. 
Consistency- Firm. 
Colour -May be yellow (fatty change), red (congestion), green (cholestaisis), or pale gray (recent nodules due to absence of pigment). 

Morphologically  According to the size of these nodules, cirrhosis can be classified
    
    Micronodular (regular) cirrhosis. Small nodules 2-3 mm.in diameter.
    Macronodular (irregular) cirrhosis, nodules up to one cm in diameter.
    Mixed cirrhosis is the end stage of all types of cirrhosis
    
Microscopic picture 

1 Regenerating nodulesn- Proliferated hepatocytes arranged in thick plates and separated by blood sinusoids.  Central vein in abnormal sites (eccentric) - Hepatocytes may be small , large , or binucleated 

2- Fibrosis- It replaces damaged hepatocytes. It develops at certain sites:-
a-perivenular    b -perisinusoidal    c -pericellular  and d -in relation to portal tracts.

- It may be young, cellular and highly vascular or mature with diminished vasculsarity. It encloses groups of hepatocytes, lobules or regenerating nodules.

-As a result of hepatocyte injury and fibrosis, there’s loss of normal liver architecture including the lobular and acinar pattern as well as the liver cell plates 

3- Bile ductular proliferation:- Occurs in the fibrous septa.Focal choestaisis with feathery degeneration of hepatocytes occur at the margins of regenerating nodules. It becomes diffuse terminally.  

4- Inflammatory cells:-   Lymphocytes, macrophages and plasma cells infiltrate the fibrous septa and regenerating nodules 

Etiological classification of cirrhosis

Congenital Occurs at childhood
- congenital syphilis   
  
Hereditary diseases:- 
a. Primary idiopathic haemochromatosis      b. Thalassemia      c. Wilson’s disease      d.α 1-antitrypsin deficien e. glycogen storage disease

Acquired

-Cryptogenic (10-50%).             
-Alcoholic (30-70%)
-Post viral  (15-20%)                
- Biliary cirrhosis (16%) primary or secondary. 

Graves disease 

Graves disease is an organ-specific autoimmune disorder that results in thyrotoxicosis due to overstimulation of the thyroid gland by autoantibodies. 
- It is the most common form of thyrotoxicosis, females being affected more than males by 8: 1. 
- It is usually associated with a diffuse enlargement of the thyroid.

Pathogenesis
 
IgG-type immunoglobulins bind to TSH membrane receptors and cause prolonged stimulation of the thyroid, lasting for as long as 12 hours 
(cf. 1 hour for TSH). The autoantibody binds at a site different to the hormone-binding locus and is termed the TSH-receptor autoantibody (TRAb); 95% of Graves’ disease patients are positive for TRAbs

Gross features 
- The thyroid gland is diffusely and moderately enlarged
- It is usually smooth, soft, and congested  

Histologically
- the gland shows diffuse hypertrophy and hyperplasia of acinar epithelium, reduction of stored colloid and local accumulations of lymphocytes with lymphoid follicle formation.

Clinical features

- Exophthalmos (protrusion of the eyeballs in their sockets)—due to the infiltration of orbital tissues by fat, mucopolysaccharides and lymphocytes. May cause compression of the optic nerve, hence blindness. However, only about 5% of Graves’ patients show signs of exophthalmos.
- Thyroid acropachy—enlargement of fingernails. 
- Pretibial myxoedema—accumulation of mucoproteins in the deep dermis of the skin.

Treatment is as for thyrotoxicosis.

Asthma

Asthma is

(1) An obstructive lung disease characterized by narrowing of the airways.

Inflammation of the airways is a major component of asthma.

(2) Common symptoms are dyspnea, wheezing on expiration, and coughing.

(3) Two types:

(a) Extrinsic (allergic, atopic) asthma

(i) An atopic allergy caused by a type I immediate hypersensitivity immune reaction to an allergen.

(ii) Seen in children, adults.

(b) Intrinsic (nonallergic) asthma

(i) Not caused by an allergic reaction.

(ii) Mostly seen in adults.

The disorder is a chronic inflammatory condition in which the airways develop increased responsiveness to various stimuli, characterized by bronchial hyper-responsiveness, inflammation, increased mucus production, and intermittent airway obstruction.

Signs and symptoms

• The clinical hallmarks of an attack are shortness of breath (dyspnea) and wheezing
• A cough—sometimes producing clear sputum—may also be present
• The onset is often sudden; there is a "sense of constriction" in the chest, breathing becomes difficult, and wheezing occurs
• Signs of an asthmatic episode are wheezing, rapid breathing (tachypnea), prolonged expiration, a rapid heart rate (tachycardia), rhonchous lung sounds (audible through a stethoscope), and over-inflation of the chest.
• During very severe attacks asthma sufferer can turn blue due to lack of oxygen , can experience chest pain or even loss of consciousness, may lead to respiratory arrest and death

Pathophysiology

Bronchoconstriction : asthma is the result of an abnormal immune response in the bronchial airways. The airways of asthmatics are "hypersensitive" to certain triggers, also known as stimuli, these stimuli include allergens, medications , air pollution, early child hood infection, exercise, emotional stress

Bronchial inflammation asthma resulting from an immune response to inhaled allergens—are the best understood of the causal factors. In both asthmatics and non-asthmatics, inhaled allergens that find their way to the inner airways are ingested by a type of cell known as antigen presenting cells These activate an humoral immune response. The humoral immune system produces antibodies against the inhaled allergen. Later, when an asthmatic inhales the same allergen, these antibodies "recognize" it and activate a humoral response. Inflammation results: chemicals are produced that cause the airways to constrict and release more mucus, and the cell-mediated arm of the immune system is activated. The inflammatory response is responsible for the clinical manifestations of an asthma attack

Symptomatic Treatment

Episodes of wheeze and shortness of breath generally respond to inhaled  bronchodilators which work by relaxing the smooth muscle in the walls of the bronchi., More severe episodes may need short courses of inhaled, oral, or intravenous steroids which suppress  inflammation and reduce the swelling of the lining of the airway.

Bronchodilators (usually inhaled)

Short-acting selective  beta2-adrenoceptor agonists(salbutamol, terbutaline)

less selective adrenergic agonists, such as inhaled epinephrine and ephedrine tablets

Antimuscarinics

Systemic steroids

Oxygen to alleviate the hypoxia that is the result of extreme asthma attacks.

If chronic acid indigestion ( GERD) is part of the attack, it is necessary to treat it as well or it will restart the inflammatory process

Preventive Treatment

most effective preventive medication are

Inhaled  corticosteroids

Long-acting beta2-adrenoceptor agonists

Leukotriene modifiers

Mast cell stabilizers

Methylxanthines (theophylline and aminophylline),

Antihistamines, often used to treat allergic symptoms