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General Pathology - NEETMDS- courses
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General Pathology

Rickettsial Diseases

Epidemic Typhus

An acute, severe, febrile, louse-borne disease caused by Rickettsia prowazekii, characterized by prolonged high fever, intractable headache, and a maculopapular rash.

Symptoms, Signs, and Prognosis

After an incubation period of 7 to 14 days, fever, headache, and prostration suddenly occur. Temperature reaches 40° C (104° F) in several days and remains high, with slight morning remission, for about 2 wk. Headache is generalized and intense. Small pink macules appear on the 4th to 6th day, usually in the axillae and on the upper trunk; they rapidly cover the body, generally excluding the face, soles, and palms. Later the rash becomes dark and maculopapular; in severe cases, the rash becomes petechial and hemorrhagic. Splenomegaly occurs in some cases. Hypotension occurs in most seriously ill patients; vascular collapse, renal insufficiency, encephalitic signs, ecchymosis with gangrene, and pneumonia are poor prognostic signs. Fatalities are rare in children < 10 yr, but mortality increases with age and may reach 60% in untreated persons > 50 yr.

Eosinophilia:
Causes

-Allergic disorders.
-Parasitic infection.
-Skin diseases.
-Pulmonary eosinophilia.
-Myeloproliferative lesions and Hodgkin's disease.

Cardiac arrhythmia

Cardiac arrhythmia is a group of conditions in which muscle contraction of the heart is irregular for any reason.

Tachycardia :A rhythm of the heart at a rate of more than 100 beats/minute , palpitation present
Causes : stress, caffeine, alcohol, hyperthyroidism or drugs

Bradycardia : slow rhythm of the heart at a rate less than 60 beats/min 

Atrial Arrhythmias 

- Atrial fibrillation

Atrial Dysrhythmias 

- Premature atrial contraction
- Atrial flutter
- Supraventricular tachycardia
- Sick sinus syndrome

Ventricular Arrhythmias 

- Ventricular fibrillation

Ventricular Dysrhythmias 

- Premature ventricular contraction
- Pulseless electrical activity
- Ventricular tachycardia
- Asystole

Heart Blocks 

- First degree heart block
- Second degree heart block 
o    Type 1 Second degree heart block a.k.a. Mobitz I or Wenckebach
o    Type 2 Second degree heart block a.k.a. Mobitz II
- Third degree heart block a.k.a. complete heart block

Atrial fibrillation

Atrial fibrillation  is a cardiac arrhythmia (an abnormality of heart rate or rhythm) originating in the atria.
AF is the most common cardiac arrhythmia

Signs and symptoms

Rapid and irregular heart rates
palpitations, exercise intolerance, and occasionally produce angina and congestive symptoms of shortness of breath or edema
Paroxysmal atrial fibrillation is the episodic occurence of the arrhythmia  Episodes may occur with sleep or with exercise

Diagnosis: 

Electrocardiogram
- absence of P waves
- unorganized electrical activity in their place
- irregularity of R-R interval due to irregular conduction of impulses to the ventricles

Causes:

- Arterial hypertension
- Mitral valve disease (e.g. due to rheumatic heart disease or mitral valve prolapse)
- Heart surgery
- Coronary heart disease
- Excessive alcohol consumption ("binge drinking" or "holiday heart")
- Hyperthyroidism
- Hyperstimulation of the vagus nerve, usually by having large meals

Treatment

Rate control by 
Beta blockers (e.g. metoprolol)
Digoxin
Calcium channel blockers (e.g. verapamil)

Rhythm control

Electrical cardioverion by application of a DC electrical shock
Chemical cardioversion is performed with drugs eg amiodarone

Radiofrequency ablation : uses radiofrequency energy to destroy abnormal electrical pathways in heart tissue It is used in recurrent AF

In confirmed AF, anticoagulant treatment is a crucial way to prevent stroke

Atrial flutter

Atrial flutter is a regular, rhythmic tachycardia originating in the atria. The rate in the atria is over 220 beats/minute, and typically about 300 beats/minute

he morphology on the surface EKG is typically a sawtooth pattern.

The ventricles do not beat as fast as the atria in atrial flutter

Supraventricular tachycardia

apid rhythm of the heart in which the origin of the electrical signal is either the atria or the AV node
it is important to determine whether a wide-complex tachycardia is an SVT or a ventricular tachycardia, since they are treated differently

Sick sinus syndrome : a group of abnormal heartbeats (arrhythmias) presumably caused by a malfunction of the sinus node, the heart's "natural" pacemaker.

Ventricular fibrillation

is a cardiac condition which consists of a lack of coordination of the contraction of the muscle tissue of the large chambers of the heart. The ventricular muscle twitches randomly, rather than contracting in unison, and so the ventricles fail to pump blood into the arteries and into systemic circulation.

Ventricular fibrillation is a medical emergency: if the arrhythmia continues for more than a few seconds, blood circulation will cease, as evidenced by lack of pulse, blood pressure and respiration, and death will occur. Ventricular fibrillation is a cause of cardiac arrest and sudden cardiac death
 

ADRENAL INSUFFICIENCY

Adrenocortical hypofunction is either primary (adrenocrtical) or secondary (ACTH deficiency). Primary insufficiency is divided into acute & chronic. 
Acute Adrenocortical Insufficiency occurs most commonly in the following clinical settings
- massive adrenal hemorrhage including  Waterhouse-Friderichsen syndrome 
- Sudden withdrawal of long-term corticosteroid therapy
- Stress in those with chronic adrenal insufficiency 

Massive adrenal hemorrhage may destroy the adrenal cortex sufficiently to cause acute adrenocortical 
insufficiency. This condition may occur 
1. in patients maintained on anticoagulant therapy 
2. in postoperative patients who develop DIC
3. during pregnancy 
4. in patients suffering from overwhelming sepsis (Waterhouse-Friderichsen syndrome) 


Waterhouse-Friderichsen syndrome is a catastrophic syndrome classically associated with Neisseria meningitidis septicemia but can also be caused by other organisms, including Pseudomonas species, pneumococci & Haemophilus influenzae. The pathogenesis of the syndrome remains unclear, but probably involves endotoxin-induced vascular injury with associated DIC.


Chronic adrenocortical insufficiency (Addison disease) results from progressive destruction of the adrenal cortex. More than 90% of all cases are attributable to one of four disorders: 
1. autoimmune adrenalitis (the most common cause; 70% of cases) 
2. tuberculosis &fungal infections 
3. AIDS
4. Metastatic cancers   
In such primary diseases, there is hyperpigmentation of the skin oral mucosa due to high levels of MSH (associated with high levels of ACTH).

Autoimmune adrenalitis is due to autoimmune destruction of steroid-producing cells. It is either isolated associated other autoimmune diseases, such as Hashimoto disease, pernicious anemia, etc. 

Infections, particularly tuberculous and fungal

Tuberculous adrenalitis, which once was responsible for as many as 90% of cases of Addison disease, has become less common with the advent of antituberculous therapy. When present, tuberculous adrenalitis is usually associated with active infection elsewhere, particularly the lungs and genitourinary tract. Among fungi, disseminated infections caused by Histoplasma capsulatum is the main cause. 

AIDS patients are at risk for developing adrenal insufficiency from several infectious (cytomegalovirus, Mycobacterium avium-intracellulare) and noninfectious (Kaposi sarcoma) complications.
 
Metastatic neoplasms: the adrenals are a fairly common site for metastases in persons with disseminated carcinomas. Although adrenal function is preserved in most such patients, the metastatic growths sometimes destroy sufficient adrenal cortex to produce a degree of adrenal insufficiency. Carcinomas of the lung and breast are the major primary sources. 

Secondary Adrenocortical Insufficiency

Any disorder of the hypothalamus and pituitary, such as metastatic cancer, infection, infarction, or irradiation, that reduces the output of ACTH leads to a syndrome of hypoadrenalism having many similarities to Addison disease. In such secondary disease, the hyperpigmentation of primary Addison disease is lacking because melanotropic hormone levels are low. 

Secondary adrenocortical insufficiency is characterized by low serum ACTH and a prompt rise in plasma cortisol levels in response to ACTH administration. 

Pathological features of adrenocortical deficiency 

- The appearance of the adrenal glands varies with the cause of the insufficiency. 
- In secondary hypoadrenalism the adrenals are reduced to small, uniform, thin rim of atrophic yellow cortex that surrounds a central, intact medulla. Histologically, there is atrophy of cortical cells with loss of cytoplasmic lipid, particularly in the zonae fasciculata and reticularis. 
- In primary autoimmune adrenalitis there is also atrophy of the cortex associated with a variable lymphoid infiltrate that may extend into the subjacent medulla. The medulla is otherwise normal.  
- In tuberculosis or fungal diseases there is granulomatous inflammatory reaction. Demonstration of the responsible organism may require the use of special stains.  
- With metastatic carcinoma, the adrenals are enlarged and their normal architecture is obscured by the infiltrating neoplasm.  
 

Molecular techniques

Different molecular techniques such as fluorescent in situ hybridization, Southern blot, etc... can be used to detect genetic diseases.

Cytopathologic techniques

Cytopathology is the study of cells from various body sites to determine the cause or nature of disease.

Applications of cytopathology:

  1. Screening for the early detection of asymptomatic cancer

2. Diagnosis of symptomatic cancer

3. Surveillance of patients treated for cancer

Cytopathologic methods

There are different cytopathologic methods including:

1. Fine-needle aspiration cytology (FNAC) -In FNAC, cells are obtained by aspirating the diseased organ using a very thin needle under negative pressure.

Superficial organs (e.g. thyroid, breast, lymph nodes, skin and soft tissues) can be easily aspirated.

Deep organs, such as the lung, mediastinum, liver, pancreas, kidney, adrenal gland, and retroperitoneum are aspirated with guidance by fluoroscopy, ultrasound or CT scan.

  1. Exfoliative cytology

Refers to the examination of cells that are shed spontaneously into body fluids or secretions. Examples include sputum, cerebrospinal fluid, urine, effusions in body cavities (pleura, pericardium, peritoneum), nipple discharge and vaginal discharge.

  1. Abrasive cytology

Refers to methods by which cells are dislodged by various tools from body surfaces (skin, mucous membranes, and serous membranes). E.g. preparation of cervical smears with a spatula or a small brush to detect cancer of the uterine cervix at early stages.

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.

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