Chronic myelocytic leukaemia
Commoner in adults (except the Juvenile type)

Features:

- Anaemia.
- Massive splenomegaly
- Bleeding tendencies.
- Sternal tenderness.
- Gout and skin manifestations

Blood picture:

- Marked leucocytosis of 50,-1000,000 cu.mm, often more
- Immature cells of the series with 20-50 % myelocytes
- Blasts form upto 5-10% of cells
- Basophils may be increased
- Leuocyte alkaline phosphate is reduced
- Anaemia with reticutosis and nucleated RBC
- Platelets initially high levels may fall later if patient goes into blast crisis.

Bone marrow:
- Hyper cellular marrow.
- Myeloid hyperplasia with more of immature forms, persominatly myelocytes.

Chromosomal finding. Philadelphia (Phi) chromosome is positive adult cases .It is a short chromosome due to deletion  of long arm of chromosome 22 (translocated to no.9),

Juvenile type :- This is Ph1 negative  has more nodal enlargement and has a worse prognosis, with a greater proneness to infections and haemorrhage
 

Emphysema

Emphysema is a chronic lung disease. It is often caused by exposure to toxic chemicals or long-term exposure to tobacco smoke.

Signs and symptoms

loss of elasticity of the lung tissue

destruction of structures supporting the alveoli

destruction of capillaries feeding the alveoli

The result is that the small airways collapse during expiration, leading to an obstructive form of lung disease

Features are: shortness of breath on exertion

 hyperventilation and an expanded chest.

As emphysema progresses, clubbing of the fingers may be observed, a feature of longstanding hypoxia.

Emphysema patients are sometimes referred to as "pink puffers". This is because emphysema sufferers may hyperventilate to maintain adequate blood oxygen levels. Hyperventilation explains why emphysema patients do not appear cyanotic as chronic bronchitis (another COPD disorder) sufferers often do; hence they are "pink" puffers (adequate oxygen levels in the blood) and not "blue" bloaters (cyanosis; inadequate oxygen in the blood).

Diagnosis

spirometry (lung function testing), including diffusion testing

X-rays,  high resolution spiral chest CT-scan,

Bronchoscopy, blood tests, pulse oximetry and arterial blood gas sampling.

Pathophysiology :

Permanent destructive enlargement of the airspaces distal to the terminal bronchioles without obvious fibrosis

Oxygen is inhaled in normal breathing

When toxins such as smoke are breathed into the lungs, the particles are trapped by the hairs and cannot be exhaled, leading to a localised inflammatory response. Chemicals released during the inflammatory response (trypsin, elastase, etc.) are released and begin breaking down the walls of alveoli. This leads to fewer but larger alveoli, with a decreased surface area and a decreased ability to take up oxygen and loose carbon dioxide. The activity of another molecule called alpha 1-antitrypsin normally neutralizes the destructive action of one of these damaging molecules.

After a prolonged period, hyperventilation becomes inadequate to maintain high enough oxygen levels in the blood, and the body compensates by vasoconstricting appropriate vessels. This leads to pulmonary hypertension. This leads to enlargement and increased strain on the right side of the heart, which in turn leads to peripheral edema (swelling of the peripherals) as blood gets backed up in the systemic circulation, causing fluid to leave the circulatory system and accumulate in the tissues.

Emphysema occurs in a higher proportion in patient with decreased alpha 1-antitrypsin (A1AT) levels

Prognosis and treatment

Emphysema is an irreversible degenerative condition

Supportive  treatmentis by supporting the breathing with anticholinergics, bronchodilators and (inhaled or oral) steroid medication, and supplemental oxygen as required

Lung volume reduction surgery (LVRS) can improve the quality of life for only  selected patients.

INFARCTION

 An infarct is an area of ischemic necrosis caused by occlusion of either the arterial supply or the venous drainage in a particular tissue 

 Nearly 99% of all infarcts result from thrombotic or embolic events 
 
other mechanisms include: local vasospasm, expansion of an atheroma, extrinsic compression of a vessel (e.g., by tumor); vessel twisting (e.g., in testicular torsion or bowel volvulus; and traumatic vessel rupture

MORPHOLOGY OF INFARCTS 

 infarcts may be either red (hemorrhagic) or white (anemic) and may be either septic or aseptic 

 All infarcts tend to be wedge-shaped, with the occluded vessel at the apex and the periphery of the organ forming the base 
 
 The margins of both types of infarcts tend to become better defined with time 
 
 The dominant histological characteristic of infarction is ischemic coagulative necrosis 
 
 most infarcts are ultimately replaced by scar. The brain is an exception, it results in liquefactive necrosis 
 
 RED INFARCTS:
occur in 
(1) venous occlusions (such as in ovarian torsion) 
(2) loose tissues (like lung) that allow blood to collect in the infarcted zone 
(3) tissues with dual circulations (lung and small intestine) 
(4) previously congested tissues because of sluggish venous outflow 
(5) when flow is re-established to a site of previous arterial occlusion and necrosis 

WHITE INFARCTS 

occur with: 
1) arterial occlusions 
2) solid organs (such as heart, spleen, and kidney).

Septic infarctions - occur when bacterial vegetations from a heart valve embolize or when microbes seed an area of necrotic tissue. - the infarct is converted into an abscess, with a correspondingly greater inflammatory response

FACTORS THAT INFLUENCE DEVELOPMENT OF AN INFARCT
- nature of the vascular supply 
- rate of development of the occlusion (collateral circulation ) 
- vulnerability to hypoxia - Neurons undergo irreversible damage 
- 3 to 4 minutes of ischemia. - Myocardial cells die after only 20 to 30 minutes of ischemia 
- the oxygen content of blood
 

Infections caused by N. meningiditis

1.  Bacteremia without sepsis.  Organism spreads to blood but no major reaction.

2.  Meningococcemia without meningitis.  Fever, headache, petechia, hypotension, disseminated       intravascular coagulation.  The Waterhouse-Friderichsen Syndrome is a rapid, progressive meningococcemia with shock, organ failure, adrenal necrosis, and death.

3.  Meningitis with meningococcemia.  Sudden onset fever, chills, headache, confusion, nuchal rigidity.  This occurs rapidly.

4.  Meningoencephalitis.  Patients are deeply comatose.

Diagnosis made by examining CSF.

Diseases from Str. pyogenes (Group A strep)

1.  Streptococcal pharyngitis.  Most frequent Group A infection.  Throat has gray-white exudate.  Infection may become systemic into blood, sinuses, jugular vein, meninges.  In less than a week the M-protein and capsule production decrease, and transmission declines.

2.  Skin infections, such as impetigo.  Especially in children.  Different M-proteins than in pharyngitis.  Skin infections associated with edema and red streaking (characteristic).

3.  Necrotizing fasciitis/myositis.  Infection of deeper tissue advances despite antibiotics.

4. Scarlet fever.  Caused by phage-associated erythrogenic toxin-producing strains.  Toxins cause cardiac, renal, and other systemic failures.  Rash is very red with a sand-papery feel and shedding of superficial skin.

5.  Toxic Shock Syndrome.  Parallels the toxic shock caused by TSST-carrying Staph. aureus.

6.  Non-suppurative, post-infection diseases. 

Rheumatic fever (myocarditis, cardiac valve disease, polyarthralgia, rashes.  Occurs two  weeks after a pharyngeal infection)

Glomerulonephritis (Occurs two weeks after pharyngeal or skin infections.  Often due to immunologic reaction to M-protein type 12)

Avitaminoses -  Vitamin deficiencies are more commonly secondary disorders associated with malabsorption conditions and chronic alcoholism.

A. Vitamin A - (retinoids, fat soluble compounds derived from ß-carotene) The best-known effect of deficiency is an inability to see in weak light (night blindness due to decreased rhodopsin).
-> The pathology is also characterized by skin lesions (rash on the extremities with punctate erythematous lesions). In malnourished children, vitamin A supplements reduce the incidence of infections such as measles, even in children without signs of preexisting deficiency.

B. Vitamin D - (1, 25 OH2 D3) Deficiency produces osteomalacia (called rickets in children). Many of the effects of osteomalacia overlap with the more common osteoporosis, but the two disordersare significantly different.
-> The specific alteration in osteomalacia and rickets is a failure of mineralization of the osteoid matrix resulting in decreased appositional bone growth. 

C. Vitamin E - Very rare. Occurs as a secondary disorder in conditions associated with fat maladsorption such as cystic fibrosis, pancreatitis, and cholestasis (bile-flow obstruction).
-> Vitamin E deficiency causes a neurological disorder characterized by sensory loss, ataxia and retinitis pigmentosa due to free radical mediated neuronal damage.

D. Vitamin K - (phylloquinone) Present in most leafy plants and also synthesized by intestinal bacteria. Vitamin K is required for the production of specific clotting factors and a deficiency is characterized by impaired coagulation (elevated clotting times). Although this can occur in newborns that are given breast milk low in vitamin K, the deficiency is almost always secondarily associated with the use of certain anti-coagulants or disorders such as obstructive jaundice, celiac, or pancreatic disease.

 E. Thiamine - (B1) The deficiency is known as beriberi. Thiamine deficiency is characterized by a peripheral neuropathy that affects sensation particularly in the legs (associated with demyelination of peripheral nerves), in more severe cases Korsakoff syndrome (neuropathy characterized by impaired ocular motility, ataxia, and mental confusion) and cardiomyopathy can occur.

F. Nicotinamide (niacin) - The deficiency is known as pellagra. Primary deficiencies are associated with diets that consist primarily of a single low quality protein source (i.e. corn). It results most commonly as a complication of alcoholism.

-> The pathology is characterized by hyperkeratosis and vesiculation of skin, atrophy of the tongue epithelium, and a neuropathy that can affect cortex and peripheral neurons.

- Initial symptoms include a smooth, red tongue, a sore mouth, and ulceration of the inside of the cheeks.

- The skin on the neck, chest, and back of the hands may become brown and scaly. 

- Often there is nausea, vomiting, and diarrhea. There may also be insomnia, depression, confusion, and rapid changes of mood. Long-standing pellagra can result in dementia and death.

G. Vitamin B12 - (cobalamin) Because cobalamin is synthesized by intestinal bacteria and is widely available in many foods, deficiencies are almost always secondary disorders associated with gastric atrophy (and decreased uptake via intrinsic factor), microbial proliferation (AIDS), long-term antacids, chronic alcoholism, idiopathic (age-related).

In addition to anemia, the primary clinical symptoms include a sensory neuropathy (polyneuropathy), sclerosis of the spinal cord and atrophy of some mucous tissues.

H. Vitamin C - (ascorbic acid) The classic deficiency is known as scurvy. The essential pathology involves an inability to produce mature collagen and hence affects connective tissue.

This is characterized by an inability to synthesize osteoid and dentin (and results in decreased wound healing) and a loss of integrity of blood vessel walls.

Oral lesions are only a feature of the advanced form of the disease; early signs include fatigue, dermatitis, and purpura. There can be abnormalities in the growing bones of infants. 

I. Vitamin B6 - (Pyridoxine) A deficiency can lead to peripheral neuropathy, most commonly associated with multivitamin B deficiencies in malnutrition and alcoholism. 

V. Major Minerals - Sodium, potassium, chlorine, and magnesium are required for life but dietary deficiencies do not develop.
A. Iodine - Essential for the synthesis of thyroid hormones, and severe iodine deficiency is  associated with hypothyroidism. The compensatory activity of the thyroid gland causes a  characteristic enlargement called goiter.

B. Calcium - Required for bone mineralization, the RDA for adults is 800 mg/day. Clinical trials have shown that 1000-2000 mg/day can delay the bone loss observed in the elderly and decrease the risk of osteoporosis. See also section IV B.

VI. Trace Elements - At least 10 elements (examples: Co, Mn, Si) are required in minute amounts for normal development and metabolism.

A. Zinc - A deficiency can result from inadequate amounts given during total parenteral nutrition or as a secondary effect of acrodermatitis enteropathica (autosomal recessive trait characterized by alopecia, dermatitis, and diarrhea - the disease responds to administration of zinc).

B. Copper - Deficiencies are rare and primarily associated with malabsorption syndromes and total parenteral nutrition. Copper is required for normal hematopoiesis and bone growth. A deficiency resembles iron deficiency anemia and osteoporosis.

C. Fluoride - Levels in drinking water greater than 1 ppm cause mottling of teeth and in areas with chronic naturally induced fluorosis there is abnormal calcification of ligaments and tendons.