NEET MDS Lessons
General Pathology
DIABETES MELLITUS
a group of metabolic disorders sharing the common underlying characteristic of hyperglycemia.
Diabetes is an important disease because
1. It is common (affects 7% of the population).
2. It increases the risk of atherosclerotic coronary artery and cerebrovascular diseases.
3. It is a leading cause of
a. Chronic renal failure
b. Adult-onset blindness
c. Non traumatic lower extremity amputations (due to gangrene)
Classification
Diabetes is divided into two broad classes:
1. Type1 diabetes (10%): characterized by an absolute deficiency of insulin secretion caused by pancreatic βcell destruction, usually as a result of an autoimmune attack.
2. Type2 diabetes (80%): caused by a combination of peripheral resistance to insulin action and an inadequate secretion of insulin from the pancreatic β cells in response to elevated blood glucose levels.
The long-term complications in kidneys, eyes, nerves, and blood vessels are the same in both types.
Pathogenesis
Type 1 diabetes is an autoimmune disease and as in all such diseases, genetic susceptibility and environmental influences play important roles in the pathogenesis. The islet destruction is caused primarily by T lymphocytes reacting against immunologic epitopes on the insulin hormone located within β-cell; this results in a reduction of β-cell mass. The reactive T cells include CD4+ T cells of the TH1 subset, which cause tissue injury by activating macrophages, and CD8+ cytotoxic T lymphocytes; these directly kill β cells and also secrete cytokines that activate further macrophages. The islets show cellular necrosis and lymphocytic infiltration (insulitis). Autoantibodies against a variety of β-cell antigens, including insulin are also detected in the blood and may also contribute to islet damage.
Type 2 Diabetes Mellitus: the pathogenesis remains unsettled. Environmental influences, such as inactive life style and dietary habits that eventuates in obesity, clearly have a role. Nevertheless, genetic factors are even more important than in type 1 diabetes. Among first-degree relatives with type 2 diabetes the risk of developing the disease is 20% to 40%, as compared with 5% in the general population.
The two metabolic defects that characterize type 2 diabetes are 1. A decreased ability of peripheral tissues to respond to insulin (insulin resistance) and 2. β-cell dysfunction manifested as inadequate insulin secretion in the face of hyperglycemia. In most cases, insulin resistance is the primary event and is followed by increasing degrees of β-cell dysfunction.
Morphology of Diabetes and Its Late Complications
The important morphologic changes are related to the many late systemic complications of diabetes and thus are likely to be found in arteries (macrovascular disease), basement membranes of small vessels (microangiopathy), kidneys (diabetic nephropathy), retina (retinopathy), and nerves (neuropathy). These changes are seen in both type 1 and type 2 diabetes.
The changes are divided into pancreatic & extrapancreatic
A. Pancreatic changes are inconstant and are more commonly associated with type 1 than with type 2 diabetes.
One or more of the following alterations may be present.
1. Reduction in the number and size of islets
2. Leukocytic infiltration of the islets (insulitis) principally byT lymphocytes.
3. Amyloid replacement of islets; which is seen in advanced stages
B. Extrapancreatic changes
1. Diabetic macrovascular disease is reflected as accelerated atherosclerosis affecting the aorta and other large and medium-sized arteries including the coronaries. Myocardial infarction is the most common cause of death in diabetics. Gangrene of the lower limbs due to advanced vascular disease, is about 100 times more common in diabetics than in the general population.
2. Hyaline arteriolosclerosis
is the vascular lesion associated with hypertension. It is both more prevalent and more severe in diabetics than in nondiabetics, but it is not specific for diabetes and may be seen in elderly nondiabetics without hypertension.
3. Diabetic microangiopathy
is one of the most consistent morphologic features of diabetes, which reflected morphologically as diffuse thickening of basement membranes. The thickening is most evident in the capillaries of the retina, renal glomeruli, and peripheral nerves. The thickened capillary basement membranes are associated with leakiness to plasma proteins. The microangiopathy underlies the development of diabetic nephropathy, retinopathy, and some forms of neuropathy.
4. Diabetic Nephropathy: renal failure is second only to myocardial infarction as a cause of death from diabetes.
Three lesions encountered are:
1. Glomerular lesions
2. Renal vascular lesions, principally arteriolosclerosis; and
3. Pyelonephritis, including necrotizing papillitis.
Glomerular lesions: these include
a. diffuse glomerular capillary basement membrane thickening
b. diffuse glomerular sclerosis : diffuse increase in mesangial matrix; always associated with the above.
c. nodular glomerulosclerosis (Kimmelstiel-Wilson lesion) refers to a rounded deposits of a laminated matrix situated in the periphery of the glomerulus
Pyelonephritis: both acute and chronic pyelonephritis are more common & more severe
Ocular Complications of Diabetes: Visual impairment up to total blindness may occur in long-standing diabetes. The ocular involvement may take the form of
a. retinopathy
b. cataract formation
c. glaucoma
In both forms of long-standing diabetes, cardiovascular events such as myocardial infarction, renal vascular insufficiency, and cerebrovascular accidents are the most common causes of mortality. Diabetic nephropathy is a leading cause of end-stage renal disease. By 20 years after diagnosis, more than 75% of type 1 diabetics and about 20% of type 2 diabetics with overt renal disease will develop end-stage renal disease, requiring dialysis or renal transplantation.
Diabetics are plagued by an enhanced susceptibility to infections of the skin, as well as to tuberculosis,
pneumonia, and pyelonephritis. Such infections cause the deaths of about 5% of diabetics.
Pleural effusion is a medical condition where fluid accumulates in the pleural cavity which surrounds the lungs, making it hard to breathe.
Four main types of fluids can accumulate in the pleural space:
Serous fluid (hydrothorax)
Blood (hemothorax)
Lipid (chylothorax)
Pus (pyothorax or empyema)
Causes:
Pleural effusion can result from reasons such as:
- Cancer, including lung cancer or breast cancer
- Infection such as pneumonia or tuberculosis
- Autoimmune disease such as lupus erythematosus
- Heart failure
- Bleeding, often due to chest trauma (hemothorax)
- Low oncotic pressure of the blood plasma
- lymphatic obstruction
- Accidental infusion of fluids
Congestive heart failure, bacterial pneumonia and lung cancer constitute the vast majority of causes in the developed countries, although tuberculosis is a common cause in the developing world.
Diagnosis:
- Gram stain and culture - identifies bacterial infections
- Cell count and differential - differentiates exudative from transudative effusions
- Cytology - identifies cancer cells, may also identify some infective organisms
- Chemical composition including protein, lactate dehydrogenase, amylase, pH and glucose - differentiates exudative from transudative effusions
- Other tests as suggested by the clinical situation - lipids, fungal culture, viral culture, specific immunoglobulins
Chronic lymphocytic leukaemia
Commoner in middle age. It starts insidiously and often runs a long chronic course
Features:
- Lymphnode enlargement.
- Anaemia (with haemolytic element).
- Moderate splenomegaly.
- Haemorrhagic tendency in late stages.
- Infection.
Blood picture:
- Anaemia with features of haemolytic anaemia
- Total leucocytic count of 50-100,OOO/cu.mm.
- Upto 90-95% cells are lymphocytes and prolymphocytes.
- Thrombocytopenia may be seen.
Bone marrow. Lymphocytic series cells-are seen. Cells of other series are reduced,
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
Hypoparathyroidism
Hypoparathyroidism is a condition of reduced or absent PTH secretion, resulting in hypocalcaemia and hyperphosphataemia. It is far less common than hyperparathyroidism.
The causes of hypoparathyroidism are:
- Removal or damage of the parathyroid glands during thyroidectomy—most common cause of hypoparathyroidism resulting from inadvertent damage or removal.
- Autoimmune parathyroid disease—usually occurs in patients who have another autoimmune endocrine disease, e.g. Addison’s disease (autoimmune endocrine syndrome type 1).
- Congenital deficiency (DiGeorge syndrome)— rare, congenital disorder caused by arrested development of the third and fourth branchial arches, resulting in an almost complete absence of the thymus and parathyroid gland.
The effects of hypoparathyroidism are:
- ↓ release of Ca2+ from bones.
- ↓ Ca2+ reabsorption but ↑ PO 43− re absorption by the kidneys
- ↓ 1-hydroxylation of 25-hydroxyvitamin D by kidney.
Most symptoms of hypoparathyroidism are those of hypocalcaemia:
- Tetany—muscular spasm provoked by lowered plasma Ca 2+
- Convulsions.
- Paraesthesiae.
- Psychiatric disturbances, e.g. depression, confusional state and even psychosis.
- Rarely—cataracts, parkinsonian-like movement disorders, alopecia, brittle nails.
Management is by treatment with large doses of oral vitamin D; the acute phase requires intravenous calcium and calcitriol (1,25-dihydroxycholecalciferol, i.e. activated vitamin D).
Infections caused by N. meningiditis
1. Bacteremia without sepsis. Organism spreads to blood but no major reaction.
2. Meningococcemia without meningitis. Fever, headache, petechia, hypotension, disseminated intravascular coagulation. The Waterhouse-Friderichsen Syndrome is a rapid, progressive meningococcemia with shock, organ failure, adrenal necrosis, and death.
3. Meningitis with meningococcemia. Sudden onset fever, chills, headache, confusion, nuchal rigidity. This occurs rapidly.
4. Meningoencephalitis. Patients are deeply comatose.
Diagnosis made by examining CSF.
Wuchereria bancrofti, Brugia malayi (Filariasis)
- the microfilaria of Wuchereria bancrofti or Brugia malayi (nematodes) are transmitted to man by the bite of infected mosquitoes (Anophele, Aedes, Culex).
- microfilaria characteristically circulate in the bloodstream at night and enter into the lymphatics, where they mature and produce an inflammatory reaction resulting in lymphedema (elephantiasis) of the legs, scrotum, etc.