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.
 

Bronchiectasis 
- Bronchiectasis is abnormal and irreversible dilatation of the bronchi and bronchioles (greater than 2 mm in diameter) secondary to inflammatory weakening of bronchial wall.
- Occur in childhood and early adult life
- Persistent cough with copious amount of foul smelling purulent sputum

Aetiopathogenesis
Bronchial wall destruction is due to:
- Endobronchial obstruction due to foreign body
- Infection due to local obstruction or impaired defence mechanism 

Clinical conditions:
- Hereditary and congenital factors
- Obstruction
- Secondary complication

Hereditary and congenital factors:
- Congenital bronchiectasis due to developmental defects
- Cystic fibrosis causing defective secretion resulting in obstruction
- Hereditary immune defiency diseases
- Immotile cilia syndrome- immotile cilia of respiratory tract, sperms causing Kartagener’s syndrome (bronchiectasis, situs inversus and sinusitis) and male infertility
- Allergic bronchial asthma patients

Obstruction:

Localised variety in one part of bronchial system.
Obstruction can be due to
Foreign body
Endobronchial tumors
Hilar lymph nodes
Inflammatory scarring (TB)

Secondary complication:

Necrotizing pneumonia in Staph infection and TB

Morphologic changes

- Affects distal bronchi and bronchioles
- Lower lobes more frequently
- Lungs involved diffusely/segmentally
- Left lower lobe than right
- Pleura fibrotic & thickened adherent to chest wall

C/S lung: Honey-combed appearance

Microscopic examination:
Bronchiole-dilated
Bronchial epithelium-normal, ulcerated, squamous metaplasia
Bronchial wall-infiltration by ac & Ch inflammatory cells,
destruction of muscle, elastic tissue 
Lung parenchyma-fibrosis, surrounding tissue pneumonia
Pleura-fibrotic and adherent

INFLUENZA

An acute viral respiratory infection with influenza, a virus causing fever, coryza, cough, headache, malaise, and inflamed respiratory mucous membranes.

Influenza B viruses typically cause mild respiratory disease

Symptoms and Signs

mild cases:

Chills and fever up to 39 to 39.5° C

Prostration and generalized aches and pains, Headache, photophobia and retrobulbar aching

Respiratory tract symptoms may be mild at first, with scratchy sore throat, substernal burning, nonproductive cough, and sometimes coryza. Later, the lower respiratory illness becomes dominant; cough can be persistent and productive.

severe cases

sputum may be bloody. Skin is warm and flushed. Soft palate, posterior hard palate, tonsillar pillars, and posterior pharyngeal wall may be reddened, but no exudate appears. Eyes water easily, and the conjunctiva may be mildly inflamed

Encephalitis, myocarditis, and myoglobinuria are infrequent complications of influenza and, if present, usually occur during convalescence

Aneurysm

An aneurysm is a localized abnormal dilation of a blood vessel or the heart

Types:
1. True aneurysm - it involves all three layers of the arterial wall (intima, media, and adventitia) or the attenuated wall of the heart.
 e.g. Atherosclerotic, syphilitic, and congenital aneurysms, and ventricular aneurysms that follow transmural myocardial infarctions. 

2 False aneurysm 
(also called pseudo-aneurysm) is a breach in the vascular wall leading to an extravascular hematoma that freely communicates with the intravascular space ("pulsating hematoma"). 
E.g. ventricular ruptures after MI that are contained by a pericardial adhesion
E.g. a leak at the junction of a vascular graft with a natural artery.

Aneurysms are classified by macroscopic shape and size 
Saccular aneurysms 

spherical outpouchings (involving only a portion of the vessel wall, and often contain thrombi. 

Fusiform aneurysms

diffuse, circumferential dilation of a long vascular segment; 

they vary in diameter and length and can involve extensive portions of the aortic arch, abdominal aorta, or even the iliacs.

Aortic Aneurysm 

The two most important causes are: 

1- atherosclerosis : the most common cause 
It causes thinning and weakening of the media. The intimal plaques compress the underlying media and also compromise nutrient and waste diffusion from the vascular lumen into the arterial wall. The media consequently undergoes degeneration and necrosis, thus allowing the dilation of the vessel 

2- cystic medial degeneration of the arterial media. E.g. Marfan syndrome.

3- Other causes include: trauma, congenital defects (e.g., berry aneurysms), infections (mycotic aneurysms), systemic diseases, such as vasculitis.

Mycotic  Aneurysm :  
Infection of a major artery that weakens its wall is called a mycotic aneurysm

possible complications: thrombosis and rupture. 

It can originate from: 
(1) embolization of a septic thrombus, usually as a complication of infective endocarditis 
(2) extension of an adjacent suppurative process; 
(3) circulating organisms directly infecting the arterial wall 

Mycotic AAAs are atherosclerotic lesions infected by lodging of circulating microorganisms in the wall 

- e.g.  bacteremia from a primary Salmonella gastroenteritis. 

Abdominal Aortic  Aneurysm

Atherosclerotic aneurysms occur most frequently in the abdominal aorta ,the common iliac arteries, the arch, and descending parts of the thoracic aorta can also be involved 

Pathogenesis 

AAA occurs more frequently in men and rarely develops before age 50. 

Atherosclerosis is a major cause of AAA 

 hereditary defects in structural components of the aorta (e.g., defective fibrillin production in Marfan disease affects elastic tissue synthesis) 
 
 Morphology :
  Usually positioned below the renal arteries and above the bifurcation of the aorta 
  
  AAA can be saccular or fusiform 
  
  as large as 15 cm in diameter, and as long as 25 cm. 
  
  Microscopically: atherosclerosis with destruction and thinning of the underlying aortic media 
  
  the aneurysm frequently contains a laminated mural thrombus
  
  Syphilitic Aneurysm 
  
  Caused by The spirochetes T. pallidum 
  
  Tertiary stage of syphilis can cause obliterative endarteritis of the involve small vessels in any part of the body, including the vasa vasorum of the aorta 
  
  This results in ischemic medial injury, leading to aneurysmal dilation of the aorta and aortic annulus, and eventually valvular insufficiency. 
  
  valvular insufficiency and massive volume overload lead to hypertrophy of the left ventricle. The greatly enlarged hearts are sometimes called "cor bovinum" (cow's heart).
  
  CLINICAL CONSEQUENCES
  
  1.  Rupture → massive potentially fatal hemorrhage 
  2. Obstruction of downstream vessel → tissue ischemic injury
  3. Embolism → from atheroma or mural thrombus 
  4. Impingement and compression on an adjacent structure 
  5. Presentation as an abdominal mass 

Chemical Mediators In Inflammation

Can be classified as :

A. Neurogenic

Also called the Triple Response of Lewis. It involves neurogenic vasodilatation of arterioles due to antidromic axon reflex arc. The constituents of the response are:

1. arteriolar vasoconstriction followed by

2. arteriolar vasodilatation

3. swelling

B. Chemical

1. Amines: Histamine and 5 hydroxytryptamine. Released  from platelets and mast cells.

Actions: Immediate and short lived.

Dilatation of arterioles.

Increased capillary premeability.

Kinins: Bradykinin and kallidin These are present in inactive from and are  activated by kinin forming proteases

Actions:

Arteriolar dilatation.

Increased vascular permeability

Pain

Kinin forming proteases Plasmin and Kallikrein. Present as inactive precursors.

Cleavage products of complement C₃a und C₅a are called anaphylatoxins

Actions:

Histamine release from mast cells

Chemotaxis (also C₅₆₇ )

Enhance phagocytosis.

 Polymorph components

Cationic: proteins which cause

Increased permeability

Histamine release.

Chemotaxis of monocytes

Neutral proteases which:

Cleave C3 and C5 to active form

Convert Kininogen to Kinin

Increase permeability.

Acid proteases which liberate leucokinins

Slow reacting. substance of anaphylaxis: (SRS-A) is a lipid released from mast cell.

Action --Increases vascular permeability

Prostaglandins: E1 + E2 _.

Platelets are rich source

Action:

Platelets are a rich source.

Vasodilatation.

Increased permeability.

Pain.

VIII. Miscellaneous: like

Tissue lactic acid.

 Bacterial toxins.

General chromosome abnormalities
The normal human cell contains 46 chromosomes, including 22 homologous pairs of autosomes and one pair of sex chromosomes (XX for female and XY for male). A somatic cell is diploid, containing 46 chromosomes. Gametes are haploid, containing 23 chromosomes.
Aneuploidy
(a) Any deviation in the number of chromosomes, whether fewer or more, from the normal haploid number of chromosomes.
(b) Nondisjunction—a common cause of aneuploidy. It is the failure of chromosomes to pass to separate cells during meiotic or mitotic cell division.
(c) Often seen in malignant tumors.
 

Deletion: loss of a sequence of DNA from a chromosome.
 

Translocation: the separation of a chromosome and the attachment of the area of separation to another chromosome.