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. 

Hepatitis B virus (“serum hepatitis”)
- Hepatitis B (HBV) may cause acute hepatitis, a carrier state, chronic active disease, chronic persistent disease, fulminant hepatitis, or hepatocellular carcinoma  
- It is caused by a DNA virus, the virions are called Dane particles. 

b. Incubation period: ranges from 4 to 26 weeks, but averages 6 to 8 weeks.
a. Symptoms last 2 to 4 weeks, but may be asymptomatic.
c. The hepatitis B viral structure has also been named the Dane particle.

Transmission is through contact with infected blood or other body fluids. It can be transmitted by sexual intercourse and is frequently transmitted to newborns of infected mothers by exposure to maternal blood during the birth process
- Associated antigens include core antigen (HBcAg) and surface antigen (HBsAg).
The latter is usually identified in the blood for diagnosis. HbsAg is the earliest marker of acute infection.
HBeAg is also associated with the core. Its presence indicates active acute infection; when anti-HBeAg appears, the patient is no longer infective
- HBV is associated with hepatocellular carcinoma; HBsAg patients have a 200-fold greater risk of hepatocellular carcinoma than subjects who have not been exposed. 

Antibodies  
- Antibodies to surface antigen (anti-HBs) are considered protective and usually appear after the disappearance of the virus.
-Antibodies to HBcAg are not protective. They are , detected just after the appearance of HBsAg and are used to confirm infection when both HBsAg and anti HBs are absent (window).
- Antibodies to HBeAg are associated with a low risk of infectivity.

d. Infection increases the risk for hepatocellular carcinoma.

e. Laboratory assay of hepatitis B antigens and antibodies:

(1) HBsAg—present only in acute infection or chronic carriers.
(2) HBsAb—detectable only after 6 months post-initial infection. HBsAb is present in chronic infections or vaccinated individuals. Note: HBsAb is also being produced during acute infections and in chronic carriers; however, it is not detectable via current laboratory methods.
(3) HBcAg—present in either acute or chronic infection.
(4) HBeAg—present when there is active viral replication. It signifies that the carrier is highly infectious.
(5) HBeAb—appears after HBeAg. It signifies that the individual is not as contagious.

f. Vaccine: contains HBsAg.

g. Prevention: immunoglobulins (HBsAb) are available.

Cholelithiasis (Biliary calculi)
- These are insoluble material found within the biliary tract and are formed of bile constituents (cholesterol, bile pigments and calcium salts). 

Sites: - -Gall bladder, extra hepatic biliary tract.  Rarely, intrahepatic biliary tract. 

Predisposing factors:- 
- Change in the composition of bile. - It is the disturbance of the ratio between cholesterol and lecithin or bile salts which may be due to Hypercholesterolaemia which may be hereditary or the 4 F (Female, Forty, Fatty, Fertile). Drugs as clofibrate and exogenous estrogen. High intake of calories (obesity).
Increased concentration of bilirubin in bile- pigment stones
Hypercalcaemia:- Calcium carbonate stones.

2- Staisis.
3- Infection. 

Pathogenesis   i- Nucleation or initiation of stone formation:- The nidus may be cholesterol “due to supersaturation” Bacteria, parasite
RBCs or mucous.  
ii- Acceleration:- When the stone remains in the gall bladder, other constituents are added to the
nidus to form the stone. 

Complications of gall stones:- 
- Predispose to infection.- Chronic irritation leading to 
a. Ulceration       b. Squamous metaplasia & carcinoma.

THE THYROID GLAND

The thyroid gland develops embryologically from the developing pharyngeal epithelium that descends from the foramen cecum at the base of the tongue to its normal position in the anterior neck. This pattern of descent explains the occasional presence of ectopic thyroid tissue, most commonly located at the base of the tongue (lingual thyroid) or at other sites abnormally high in the neck. 

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

POLYCYTHEMIA

 It is an increase in number of RC per unit volume of blood (Hb more than 1.9.5 gms% and 18 gms% for women)
 
Causes :

True polycythemia.
- Idiopathic Polythemia vera.

- Secondary to :

    o    Hypoxia of high altitude , heart disease, chronic lung disease etc.
    o    Erythopoietin  oversecretion as in renal diseases , tumours of liver, kidney and adrenal etc.
    o    Compensatory in haemogIobinopathies
    
- Relative polycythemia due to reduction in plasma volume as in dehydration or in redistribution off fluids

Polycythemia vera: It is a myeloprolifeative disorder, usually terminating in myelosclerosis.

Features: are due to hypervolaemic circulation and tendency to tbrombosis and haemorrhage 

    -Headaches, dizziness and cardiovascular accidents.
    -Hypertension.
    -Peripheral vascular thrombosis.
    -GIT bleeding. retinal haemorrhage.
    -Gout.
    -Pruritus.

Blood Finding

-Increased Hb. PCV and RBC count.
-Leucocytosis with high alkaline  phosphatase.
-Platelets increased.

Marrow picture Hypercellular with  increase in precursors of all series 
Course Chronic course ending in myelosclerosis or acute  leukaemia.