NEET MDS Lessons
General Pathology
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.
Pheochromocytoma
Pheochromocytomas are neoplasms composed of chromaffin cells, which as their normal counterparts synthesize and release catecholamines.
1. Arise in association with one of several familial syndromes such as MEN syndromes, type 1 neurofibromatosis, von Hippel-Lindau disease, and Sturge-Weber syndrome.
2. Are extra-adrenal, occurring in sites such as the organ of Zuckerkandl and the carotid body, where they are usually called paragangliomas rather than pheochromocytomas.
3. Are bilateral; but in association with familial syndromes, this figure may rise to 50%.
4. Are malignant; frank malignancy, however, is more common in extra-adrenal tumors.
Gross features
- The size of these tumors is quite variable ranging from small to huge masses.
- Sectioning shows yellow-tan, well-defined tumor that compress the adjacent adrenal. Large lesions display areas of hemorrhage, necrosis, and cystic degeneration.
- Incubation of the fresh tissue with potassium dichromate solutions converts the tumor a dark brown color.
Microscopic features
- These tumors are composed of polygonal to spindle-shaped chromaffin cells and their supporting sustentacular cells, arranged in well-defined small nests (Zellballen)," rimmed by a rich vascular network.
- The cytoplasm is often finely granular (catecholamine-containing granules)
- The nuclei are often quite pleomorphic.
- Both capsular and vascular invasion may be encountered in benign lesions, and the presence of mitotic figures per se does not imply malignancy. Therefore, the definitive diagnosis of malignancy in pheochromocytomas is based exclusively on the presence of metastases. These may involve regional lymph nodes as well as more distant sites, including liver, lung, and bone.
The laboratory diagnosis of pheochromocytoma is based on demonstration of increased urinary excretion of free catecholamines and their metabolites, such as vanillylmandelic acid (VMA)& metanephrines.
Cardiac tamponade
A. Caused by accumulation of fluid in the pericardium. This severe condition can quickly impair ventricular filling and rapidly lead to decreased cardiac output and death.
1. Signs and symptoms include:
a. Hypotension.
b. Jugular venous distention.
c. Distant heart sounds.
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
Cor pulmonale
a failure of the right side of the heart. It is caused by prolonged high blood pressure in the right ventricle of the heart, which in turn is most often caused by pulmonary hypertension - prolonged high blood pressure in the arteries or veins of the lungs. People with heart disease, or lung diseases such as cystic fibrosis, are at greater risk.
Pathophysiology
There are several mechanisms leading to pulmonary hypertension and cor pulmonale:
Pulmonary vasoconstriction
Anatomic changes in vascularisation
Increased blood viscosity
Primary pulmonary hypertension
Causes
Acute:
• Massive pulmonary embolization
• Exacerbation of chronic cor pulmonale
Chronic:
• COPD
• Loss of lung tissue following trauma or surgery
Monocytosis:
Causes
-Infections causing lymphocytosis, especialy tuberculosis and typhoid.
-Monocytic leukaemia.
-Some auto immune diseases.
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 PO43- .
- 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.