Wilson’s disease

Caused by a decrease in ceruloplasmin, a serum protein that binds copper, resulting in metastatic copper deposits.

Common organs affected include:

(1) Liver, leading to cirrhosis.

(2) Basal ganglia.

(3) Cornea, where Kayser-Fleischer rings (greenish rings around the cornea) are observed.

HYPERPLASIA
It is the increase in the size of an organ or tissue due to increase in the number of its constituent cells. This is seen in organs made up of labile and stable cells.

Causes
I. Increased demand:
- Bone marrow in hypoxia and haemolytic states.
- Thyroid gland in puberty

2. Persistant Trauma:
- Acanthosis of the epidermis in chronic inflammations and in warts.
- Hyperplasia of oral mucosa due tooth and denture trauma.
- Mucosa at the edges of a gastric ulcer.

3. Endocrine target organ:
- Pregnancy hyperplasia of breast.
- Prostatic hyperplasia.

4. Compensatory:

Hyperplasia of kidney when the other kidney has been removed.

5. Idiopathic:
Endocrine organs like thyroid, adrenals, pituitary etc. can undergo hyperplasia with no detectable stimulus. .
 

Iron deficiency anaemia.

Absorption of iron is affected by :
- Iron stores.
- Rate of erythropoiesis
- Acid pH aids absorption.
- Phosphates and phytates in diet impair absorption.

Causes  of deficiency:

- Increased demand:
o    Growth (in children)
o    Menstruation, Pregnancy, lactation.
- Inadequate intake and absorption.
o    Dietary deficiency.
o    Achlorhydria or gastrectomy.
o    Malabsorption states.

- Chronic blood loss
o    Peptic ulcer, bleeding piles
o    Menorrhagia.
o    Hook worm infestation

Features:
- Anaemia.
- Koilonychia.
- Atrophic glossitis and angular stomatitis.
- Dysphagia-Plummer Vinson syndrome.

Blood findings:

- Microcytjc_hypochromic cells, ring cells and pessary cells.
- Anisocytosis and poikilocytosis.
- Low MCV. MCH and MCHC.
- Serum iron is low but iron binding capacity is increased

Bone marrow

Erythroid hyperplasia with imcronormoblasts. Iron stains reveal depleted stores

Differential  diagnosis .-

- Sideroblastic anaemia which is also microcytic hypochromic  but there is excess iron in the erythroid cells .Some are pyridoxine responsive.
- (ii) Thalassaemia
 

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.

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
 

Cartilage-Forming Tumors

1. Osteochondroma (Exostosis) is a relatively common benign cartilage-capped outgrowth attached by a bony stalk to the underlying skeleton. Solitary osteochondromas are usually first diagnosed in late adolescence and early adulthood (male-to-female ratio of 3:1); multiple osteochondromas become apparent during childhood, occurring as multiple hereditary exostosis, an autosomal dominant disorder. Inactivation of both copies of the EXT gene (a tumor suppressor gne) in chondrocytes is implicated in both sporadic and hereditary osteochondromas. Osteochondromas develop only in bones of endochondral origin arising at the metaphysis near the growth plate of long tubular bones, especially about the knee. They tend to stop growing once the normal growth of the skeleton is completed. Occasionally they develop from flat bones (pelvis, scapula, and ribs). Rarely, exostoses involve the short tubular bones of hands and feet.

Pathological features

• Osteochondromas vary from 1-20cm in size.
• The cap is benign hyaline cartilage. 
• Newly formed bone forms the inner portion of the head and stalk, with the stalk cortex merging with cortex of the host bone.
Osteochondromas are slow-growing masses that may be painful. Osteochondromas rarely progress to chondrosarcoma or other sarcoma, although patients with the multiple hereditary exostoses are at increased risk of malignant transformation. 

2. Chondroma 

It is a benign tumor of hyaline cartilage. When it arises within the medullary cavity, it is termed enchondroma; when on the bone surface it is called juxtacortical chondroma. Enchondromas are usually diagnosed in persons between ages 20 and 50 years; they are typically solitary and located in the metaphyseal region of tubular bones, the favored sites being the short tubular bones of the hands and feet. Ollier disease is characterized by multiple chondromas preferentially involving one side of the body. Chondromas probably develop from slowly proliferating rests of growth plate cartilage.

Pathological features 

• Enchondromas are gray-blue, translucent nodules usually smaller than 3 cm.
• Microscopically, there is well-circumscribed hyaline matrix and cytologically benign chondrocytes.
Most enchondromas are detected as incidental findings; occasionally they are painful or cause pathologic fractures. Solitary chondromas rarely undergo malignant transformation, but those associated with enchondromatosis are at increased risk. 

3. Chondrosarcomas are malignant tumors of cartilage forming tissues. They are divided into conventional chondrosarcomas and chondrosarcoma variants. Each of these categories comprises several distinct types, some defined on microscopic grounds & others on the basis of location within the affected bone, for e.g. they are divided into central (medullary), peripheral (cortical), and juxtacortical (periosteal). The common denominator of chondrosarcoma is the production of a cartilaginous matrix and the lack of direct bone formation by the tumor cells (cf osteosarcoma). Chondrosarcomas occur roughly half as frequently as osteosarcomas; most patients age 40 years or more, with men affected twice as frequently as women 

Pathological features 
Conventional chondrosarcomas arise within the medullary cavity of the bone to form an expansile glistening mass that often erodes the cortex. They exhibit malignant hyaline or myxoid stroma. Spotty calcifications are typically present. The tumor grows with broad pushing fronts into marrow spaces and the surrounding soft tissue. Tumor grade is determined by cellularity, cytologic atypia, and mitotic activity. Low-grade tumors resemble normal cartilage. Higher grade lesions contain pleomorphic chondrocytes with frequent mitotic figures with multinucleate cells and lacunae containing two or more chondrocytes. Dedifferentiated chondrosarcomas refers to the presence of a poorly differentiated sarcomatous component at the periphery of an otherwise typical low-grade chondrosarcoma. Other histologic variants include myxoid, clear-cell and mesenchymal chondrosarcomas. Chondrosarcomas commonly arise in the pelvis, shoulder, and ribs. A slowly growing lowgrade tumor causes reactive thickening of the cortex, whereas a more aggressive high-grade neoplasm destroys the cortex and forms a soft tissue mass. There is also a direct correlation between grade and biologic behavior. 
Size is another prognostic feature, with tumors larger than 10 cm being significantly more aggressive than smaller tumors. High-grade Chondrosarcomas metastasize hematogenously, preferentially to the lungs and skeleton.