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General Pathology - NEETMDS- courses
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General Pathology

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.

Urinary tract infection
Most often caused by gram-negative, rod-shaped bacteria that are normal residents of the enteric tract, especially Escherichia coli.

Clinical manifestations: 

frequent urination, dysuria, pyuria (increased PMNs), hematuria, and bacteriuria.

May lead to infection of the urinary bladder (cystitis) or kidney (pyelonephritis).

Other lung diseases

1.Sarcoidosis

1. Sarcoidosis

a. More common in African-Americans.

b. Associated with the presence of noncaseating granulomas.

Sarcoidosis is an immune system disorder characterised by non-necrotising granulomas (small inflammatory nodules). Virtually any organ can be affected, however, granulomas most often appear in the lungs or the lymph nodes.

Signs and symptoms

  • Sarcoidosis is a systemic disease that can affect any organ. Common symptoms are vague, such as fatigue unchanged by sleep, lack of energy, aches and pains, dry eyes, blurry vision, shortness of breath, a dry hacking cough or skin lesions. The cutaneous symptoms are protean, and range from rashes and noduli (small bumps) to erythema nodosum or lupus pernio
  • Renal, liver, heart or brain involvement may cause further symptoms and altered functioning. Manifestations in the eye include uveitis and retinal inflammation
  • Sarcoidosis affecting the brain or nerves is known as neurosarcoidosis.
  • Hypercalcemia (high calcium levels) and its symptoms may be the result of excessive vitamin D production
  • Sarcoidosis most often manifests as a restrictive disease of the lungs, causing a decrease in lung volume and decreased compliance (the ability to stretch). The vital capacity (full breath in, to full breath out) is decreased, and most of this air can be blown out in the first second. This means the FEV1/FVC ratio is increased from the normal of about 80%, to 90%.

Treatment

Corticosteroids, most commonly prednisone

2. Cystic fibrosis

a. Transmission: caused by a genetic mutation (nucleotide deletion) on chromosome 7, resulting in abnormal chloride channels.

b. The most common hereditary disease in Caucasians.

c. Genetic transmission: autosomal recessive.

d. Affects all exocrine glands. Organs affected include lungs, pancreas, salivary glands, and intestines. Thick secretions or mucous plugs are

seen to obstruct the pulmonary airways and intestinal tracts.

e. Is ultimately fatal.

f. Diagnostic test: sweat test—sweat contains increased amounts of chloride.

3. Atelectasis

a. Characterized by collapse of the alveoli.

b. May be caused by a deficiency of surfactant and/or hypoventilation of alveoli.

NEOPLASIA

 

 An abnormal. growth, in excess of and uncoordinated with normal tissues Which persists in the same excessive manner after cessation of the stimuli which evoked the change.

Tumours are broadly divided by their behaviors into 2 main groups, benign and malignant.

 

Features

Benign

Malignant

General

Rate of growth

Mode of growth

 

Slow

Expansile

 

Rapid

Infiltrative

Gross

Margins

 

Haemoeehage

 

Circumscribed often Encapsulated

Rare

 

III defined

 

Common

Microscopic

Arrangement

Cells

 

Nucleus

Mitosis

 

Resemble Parent Tissues

Regular and uniform in shape and size

Resembles parent Cells

Absent or scanty

 

Varying degrees of structural differentiation

Cellular pleomorphism

 

Hyper chromatic large and varying in shape and size

Numerous and abnormal

 

 

Through most tumours can be classified in the benign or malignant category . Some exhibits an intermediate behaviours.

 

CLASSIFICATION

 

Origin

Benign

Malignant

Epithelial

Surface epithelium

Glandular epithelium

Melanocytes

 

Papilloma

Adenoma

Naevus

 

Carcinoma

Adenoca cinoma

Melanocarcinoma(Melanoma)

Mesenchymal

 

Adipose tissue

Fibrous tissue

Smooth tissue

Striated muscle

Cartilage

Bone

Blood vessels

Lymphoid tissue

 

 

Lipoma

Fibroma

Leiomyoma

Rhabdomyoma

Chondroma

Osteoma

Angioma

 

 

 

Liposarcoma

Fibrosarcoma

Leimyosarcoma

Chondrosarcoma

Osteosarcoma

Angiosarcoma

Lymphoma

Some tumours can not be clearly categorized in the above table e.g.

  • Mixed tumours like fibroadenoma of the breast which is a neoplastic proliferation of both epithelial and mesenchmal tissues.
  • Teratomas which are tumours from germ cells (in the glands) and totipotent cells

(in extra gonodal sites like mediastinun, retroperitoneum and presacral region). These are composed of multiple tissues indicative of differentiation into the derivatives of the three germinal layers.

  • Hamartomas which are malformations consisting of a haphazard mass of  tissue normally present at that site.

AMYLOIDOSIS

Definition. Extra cellular  deposition of an eosinophilic hyaline homogenous material in Various organs, occurring in a variety of clinical  states.

Staining reactions

Iodine :- Brown, turning blue on addition of H2SO4 (gross and microscopic Stain).
P.A.S. – Positive  (Magenta pink).
Congo Red -Orange red which on polarisation gives green birefringence.
Von Geison's –Khaki colour.
Thioflavin T -Yellow fluorescence.

Amyloid is called typical if it given the above staining  reactions Other wise it is termed atypical or para-amyloid.

Classification 

1.    Systemic  amyloidosis associated with underlying disease (secondary),

(A) Chronic infections like 

- Tuberculosis.
- Bronchiectasis.
- Lung abscess.
- Osteomyelitis.
- Syphilis.

(B) Chronic inflammations of varied etiology:

- Rheumatoid arthritis.
- Ulcerative colitis.
- Regional enteritis.
- Lupus erythematosus.

(C) Neoplastic proliferations:

- Of immune system – Multiple myeloma, Hodgkin’s disease.
- Cancers like Renal cell carcinoma etc.


II Systemic primary amyloidosis  with no underlying cause.

III Heredofamilial types.

- Amyloidosis with mediterranean fever.
- Amyloid polyneuropathy.
- Amyloid nephrophathy
- Familial cardiac amyloidosis
- Familial cutaneous amyloid.
- Lattice corneal dystrophy

IV. Localised amyloidosis:

- Senile - in heart, brain, seminal vesicles.
- Amyloidoma of tongue, bronchial tree, skin.
- In islets of Langerhans in Diabetes mellitus.
- In medullary thyroid carcinoma.

Deposition sites
In relation to reticulin  and collagen fibres and to basement, membranes especially
subendothelial. 

Organs involved commonly are : 

Secondary amyloidosis

- Liver.
- Spleen.
- Kidney
- Lymph nodes.
- Adrenals.

Primary amyloidosis

- Heart
- Tongue and gingiva.
- Gastro intestinal tract.
- Lung.
- Wall of small vessels.

Nature and pathogenesis of amyloid
It is primarily made up of protein arranged in two patterns

- There are filaments twisted together to from the fibrils. These chemically resemble light chains of immunoglobulins
- Rods composed of stacked rings. These are made up of alpha globulin components of plasma proteins (P-components)

- In addition to these, extracts of crude amyloid contain  mucopolysacharides complement and gamma globulins.

- Origin of amyloid :- current concept is that it is a direct product of cells of the immune sustem with some abnormality in their immune response

The abnormality may be due to :
- A genetic enzyme defect.
- Prolonged antigenic challenge.
- Neoplastic transformation
- Supression of normal. Response as in induced tolerance.

Cholecystitis 
 
It is inflammation of the gall bladder. It may be acute or chronic.
In 80-90% of cases, it is associated with gall stones (Calcular cholecystis). 

Causes and pathogenesis:-
Obstruction of cystic or common bile duct- By stones, strictures, pressure from the outside, tumors etc.
Obstruction , chemical irritation of the gall bladder, Secondary bacterial infection, stone formation, trauma to the wall of gall
bladder 

Secondary bacterial infection

Usually by intestinal commensals E.coli, streptococcus fecalis. They reach the gall bladder by lymphatics. 
S.typhi reaches the gall bladder after systemic infection

Acute cholecystitis

Gall bladder is enlarged edematous and fiery red in color. 
- Wall is edematous, hyperemic, may show abscesses or gangrenous dark brown or green or black foci which may perforate.
Serous covering show fibrinosuppurative inflammation and exudation. Mucosa is edematous, hyperemic and ulcerated.
- If associated with stones, obstruction results in accumulation of pus leading to Empyaema of the gall bladder.

Fate:-  Healing by fibrosis and adhesions.

Complications:-  
- Pericholecystic abscess.
- Rupture leading to acute peritonitis.
- Ascending suppurative cholangitis and liver abscess 

Chronic cholecystitis
May follow Acute cholecystitis or starts chronic. Gall stones are usually present. 

Pathology

1. If associated with obstruction: Gall bladder is dilated. Wall may be thickened or thinned out. Contents may be clear, turbid or purulent. 
2. If not associated with obstruction: - Gall bladder is contracted, wall is markedly thickened.
3. Serosa is smooth with fibrous adhesions. Draining lymph nodes are enlarged.  
4. Wall is thickened, opaque and gray-white with red tinge.
5. Mucosa is gray- red with ulcerations and pouches.
6. Stones are usually present

Rheumatic fever

Before antibiotic therapy, this was the most common cause of valvular disease.
1. Usually preceded by a group A streptococci respiratory infection; for example, strep throat.
2. All three layers of the heart may be affected. The pathologic findings include Aschoff bodies, which are areas of focal necrosis surrounded by a dense inflammatory infiltration.

3. Most commonly affects the mitral valve, resulting in mitral valve stenosis, regurgitation, or both.

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