Summary 
Hepatitis A → ssRNA → Picornavirus → Oral–anal
Hepatitis B → dsDNA → Hepadnavirus → Sexual contact , Blood (needles), Perinatal
Hepatitis C → ssRNA → Flavivirus → Sexual contact , Blood (needles)
Hepatitis D → ssRNA → Deltavirus → Sexual contact, Blood (needles)
Hepatitis E → ssRNA → Calicivirus → Oral–anal 

Pathology

The branch of medicine dealing with the essential nature of disease, especially changes in body tissues aorgans that cause or are caused by disease. Pathology is the structural and functional manifestations of disease.

Anatomic pathology  the anatomical study of changes in the function, structure, or appearance of organs or tissues,including postmortem examinations and the study of biopsy specimens.

Cellular pathology  - Cytopathology is a diagnostic technique that examines cells from various body sites to determine the cause or the nature of disease.

Clinical pathology  pathology applied to the solution of clinical problems, especially the use of laboratory 

methods inclinical diagnosis.

Comparative pathology  that which considers human disease processes in comparison with those of other 

animals.

Oral pathology  that treating of conditions causing or resulting from morbid anatomic or functional changes in thestructures of the mouth.

Surgical pathology  the pathology of disease processes that are surgically accessible for diagnosis or treatment.

Seborrheic dermatitis is a scaly dermatitis on the scalp (dandruff) and face.
 - due to Pitysporium species
 - can be seen in AIDS as an opportunistic infection

Hyperparathyroidism

Hyperparathyroidism is defined as an elevated secretion of PTH, of which there are three main types:
1. Primary—hypersecretion of PTH by adenoma or hyperplasia of the gland.
2. Secondary—physiological increase in PTH secretions in response to hypocalcaemia of any cause.
3. Tertiary—supervention of an autonomous hypersecreting adenoma in long-standing secondary hyperparathyroidism.

Primary hyperparathyroidism
This is the most common of the parathyroid disorders, with a prevalence of about 1 per 800 
It is an important cause of hypercalcaemia.
More than 90% of patients are over 50 years of age and the condition affects females more than males by nearly 3 : 1.

Aetiology

Adenoma 75%  -> Orange−brown, well-encapsulated tumour of various size but seldom > 1 cm diameter Tumours are usually solitary, affecting only one of the parathyroids, the others often showing atrophy; they are deep seated and rarely palpable.

Primary hyperplasia 20%  ->  Diffuse enlargement of all the parathyroid glands

Parathyroid carcinoma 5% -> Usually resembles adenoma but is poorly encapsulated and invasive locally.

Effects of hyperparathyroidism
The clinical effects are the result of hypercalcaemia and bone resorption.
 

Effects of hypercalcaemia:
- Renal stones due to hypercalcuria.
- Excessive calcification of blood vessels.
- Corneal calcification.
- General muscle weakness and tiredness.
- Exacerbation of hypertension and potential shortening of the QT interval.
- Thirst and polyuria (may be dehydrated due to impaired concentrating ability of kidney).
- Anorexia and constipation    

Effects of bone resorption:
- Osteitis fibrosa—increased bone resorption with fibrous replacement in the lacunae.
- ‘Brown tumours’—haemorrhagic and cystic tumour-like areas in the bone, containing large masses of giant osteoclastic cells.
- Osteitis fibrosa cystica (von Recklinghausen disease of bone)—multiple brown tumours combined with osteitis fibrosa.
- Changes may present clinically as bone pain, fracture or deformity.

 about 50% of patients with biochemical evidence of primary hyperparathyroidism are asymptomatic.

Investigations are:
- Biochemical—increased PTH and Ca²⁺ , and decreased PO₄^3- .
- Radiological—90% normal; 10% show evidence of bone resorption, particularly phalangeal erosions.

Management is by rehydration, medical reduction in plasma calcium using bisphosphonates and eventual surgical removal of abnormal parathyroid glands.

Secondary hyperparathyroidism 

This is compensatory hyperplasia of the parathyroid glands, occurring in response to diseases of chronic low serum calcium or increased serum phosphate.
Its causes are:
- Chronic renal failure and some renal tubular disorders (most common cause).
- Steatorrhoea and other malabsorption syndromes.
- Osteomalacia and rickets. 
- Pregnancy and lactation.

Morphological changes of the parathyroid glands are:
- Hyperplastic enlargement of all parathyroid glands, but to a lesser degree than in primary hyperplasia.
- Increase in ‘water clear’ cells and chief cells of the parathyroid glands, with loss of stromal fat cells. 

Clinical manifestations—symptoms of bone resorption are dominant.

Renal osteodystrophy
Skeletal abnormalities, arising as a result of raised PTH secondary to chronic renal disease, are known as renal osteodystrophy.

Pathogenesis

renal Disease + ↓  vit. D activation , ↓ Ca 2+  reabsorption  → ↓  serum Ca 2+ → ↑ PTH → ↓ bone absorption

Abnormalities vary widely according to the nature of the renal lesion, its duration and the age of the patient, but include:
- Osteitis fibrosa .
- Rickets or osteomalacia due to reduced activation of vitamin D.
- Osteosclerosis—increased radiodensity of certain bones, particularly the parts of vertebrae adjacent to the intervertebral discs.

The investigations are both biochemical (raised PTH and normal or lowered Ca 2+ ) and radiological (bone changes).
Management is by treatment of the underlying disease and oral calcium supplements to correct hypocalcaemia.

Tertiary hyperparathyroidism
This condition, resulting from chronic overstimulation of the parathyroid glands in renal failure, causes one or more of the glands to become an autonomous hypersecreting adenoma with resultant hypercalcaemia. 

DIPHTHERIA

An acute, contagious disease caused by Corynebacterium diphtheriae, characterized by the formation of a fibrinous pseudomembrane, usually on the respiratory mucosa, and by myocardial and neural tissue damage secondary to an exotoxin.

Cutaneous diphtheria (infection of the skin) can occur when any disruption of the integument is colonized by C. diphtheriae. Lacerations, abrasions, ulcers, burns, and other wounds are potential reservoirs of the organism. Skin carriage of C. diphtheriae is also a silent reservoir of infection.

Pathology

C. diphtheriae may produce exotoxins lethal to the adjacent host cells. Occasionally, the primary site is the skin or mucosa elsewhere. The exotoxin, carried by the blood, also damages cells in distant organs, creating pathologic lesions in the respiratory passages, oropharynx, myocardium, nervous system, and kidneys.

The myocardium may show fatty degeneration or fibrosis. Degenerative changes in cranial or peripheral nerves occur chiefly in the motor fibers

In severe cases, anterior horn cells and anterior and posterior nerve roots may show damage proportional to the duration of infection before antitoxin is given. The kidneys may show a reversible interstitial nephritis with extensive cellular infiltration.

The diphtheria bacillus first destroys a layer of superficial epithelium, usually in patches, and the resulting exudate coagulates to form a grayish pseudomembrane containing bacteria, fibrin, leukocytes, and necrotic epithelial cells. However, the areas of bacterial multiplication and toxin absorption are wider and deeper than indicated by the size of the membrane formed in the wake of the spreading infection.

EMBOLISM 

An embolus is a detached intravascular solid, liquid, or gaseous mass that is carried by the blood to a site distant from its point of origin

99% due to dislodged thrombus

Types: 
1. Thrombo-embolism 
2. Fat embolism 
3. Air embolism 
4. Nitrogen embolism

 Emboli result in partial or complete vascular occlusion. 

 The consequences of thromboembolism include ischemic necrosis (infarction) of downstream tissue

PULMONARY THROMBOEMBOLISM
- 95% originate from deep veins of L.L

Special variants: - Saddle embolus: at bifurcation of Pulmonary artery

Paradoxical embolus: Passage of an embolus from venous to systemic circulation through IAD, IVD

CLINICAL CONSEQUENCE OF PULMONARY THROMBOEMBOLISM :

Most pulmonary emboli (60% to 80%) are clinically silent because they are small 

a. Organization: 60 – 80 % 
b. Sudden death, Right ventricle failure, CV collapse when more than 60 % of pulmonary vessels are obstructed. 
c. Pulmonary hemorrhage: obstruction of medium sized arteries. 
d. Pulmonary Hypertension and right ventricular failure due to multiple emboli over a long time.

Systemic thromboembolism

Emboli traveling within the arterial circulation 
80% due to intracardiac mural thrombi
2/3  Lt. ventricular failure

 The major targets are: 
 
 1. Lower limbs 75% 
 2. Brain 10% 
 3. Intestines 
 4. Kidneys 
 5. Spleen

Fat embolism 

Causes 
1. Skeletal injury (fractures of long bones ) 
2. Adipose tissue Injury

Mechanical obstruction is exacerbated by free fatty acid release from the fat globules, causing local toxic injury to endothelium. - In skeletal injury, fat embolism occurs in 90% of cases, but only 10% or less have clinical findings

 Fat embolism syndrome is characterized by 
 
 A. Pulmonary Insufficiency 
 B. Neurologic symptoms 
 C. Anemia 
 D. Thrombocytopenia 
 E. Death in 10% of the case 
 
 Symptoms appears 1-3 days after injury
 
 Tachypnea, Dyspnea, Tachycardia and Neurological symptoms
 
Air Embolism 

causes: 1. Obstetric procedures 
2. Chest wall injury 
3. Decompression sickness: in Scuba and deep-sea divers ((nitrogen )) 

 More then 100ml of air is required to produce clinical effect. 
 
 Clinical consequence
 1. Painful joints: due to rapid formation of gas bubbles within Sk. Muscles and supporting tissues. 
 2. Focal ischemia in brain and heart 
 3. Lung edema, Hemorrhage, atelectasis, emphysema, which all lead to Respiratory distress. (chokes) 
 4. caisson disease: gas emboli in the bones leads to multiple foci of ischemic necrosis, usually the heads of the femurs, tibias, and humeri
 
 Amniotic fluid embolism 
 - Mortality Rate = 20%-40% 
 - Very rare complication of labor 
 
 - due to infusion of amniotic fluid into maternal circulation via tears in placental membranes and rupture of uterine veins. 
 - sudden severe dyspnea, cyanosis, and hypotensive shock, followed by seizures, DIC and coma 
 
 - Findings: Squamous cells, languo hair, fat, mucin …..etc within the pulmonary microcirculation