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.
PERTUSSIS (Whooping Cough)
An acute, highly communicable bacterial disease caused by Bordetella pertussis and characterized by a paroxysmal or spasmodic cough that usually ends in a prolonged, high-pitched, crowing inspiration (the whoop).
Transmission is by aspiration of B. pertussis
Symptoms and Signs
The incubation period averages 7 to 14 days (maximum, 3 wk). B. pertussis invades the mucosa of the nasopharynx, trachea, bronchi, and bronchioles, increasing the secretion of mucus, which is initially thin and later viscid and tenacious. The uncomplicated disease lasts about 6 to 10 wk and consists of three stages: catarrhal, paroxysmal, and convalescent.
Actinic keratosis
1. Dry, scaly plaques with an erythematous base.
2. Similar to actinic cheilosis, which occurs along the vermilion border of the lower lip.
3. Caused by sun damage to the skin.
4. Dysplastic lesion, may be premalignant.
Respiratory Viral Diseases
Respiratory viral infections cause acute local and systemic illnesses. The common cold, influenza, pharyngitis, laryngitis (including croup), and tracheobronchitis are common.
An acute, usually afebrile, viral infection of the respiratory tract, with inflammation in any or all airways, including the nose, paranasal sinuses, throat, larynx, and sometimes the trachea and bronchi.
Etiology and Epidemiology
Picornaviruses, especially rhinoviruses and certain echoviruses and coxsackieviruses, cause the common cold. About 30 to 50% of all colds are caused by one of the > 100 serotypes of rhinoviruses.
Symptoms and Signs
Clinical symptoms and signs are nonspecific.
After an incubation period of 24 to 72 h, onset is abrupt, with a burning sensation in the nose or throat, followed by sneezing, rhinorrhea, and malaise.
Characteristically, fever is not present, particularly with a rhinovirus or coronavirus. Pharyngitis usually develops early; laryngitis and tracheobronchitis vary by person and causative agent. Nasal secretions are watery and profuse during the first days, but become more mucoid and purulent.
Cough is usually mild but often lasts into the 2nd wk.
Nevus
A nevus refers to any congenital lesion of the skin, while a nevocellular nevus specifically refers to a benign tumor of neural crest-derived cells that include modified melanocytes of various shapes (nevus cells).
- nevocellular nevi are generally tan to deep brown, uniformly pigmented, small papules with well-defined, rounded borders.
- most nevocellular nevi are subdivided into junctional, intradermal, or compound types.
- most nevocellular nevi begin as junctional nevi with nevus cells located along the basal cell layer producing small, flat lesions, which are only slightly raised.
- junctional nevi usually develop into compound nevi as nevus cells extend into the underlying superficial dermis forming cords and columns of cells (compound: nevi at junction and in the dermis).
- eventually, the junctional component of a nevocellular nevus is lost, leaving only nevus cells within the dermis, thus the term intradermal nevus.
- junctional → compound → intradermal nevus.
- although uncommon, certain nevi may evolve into a malignant melanoma, particularly those which are congenital and those which are referred to as dysplastic nevi.
- a dysplastic nevus is commonly associated with patients who have multiple scattered nevi over the entire body (dysplastic nevus syndrome) with individual lesions that have a diameter greater than 1 cm.
Connective tissue diseases
Marfan’s syndrome
a. Genetic transmission: autosomal dominant.
b. Characterized by a defective microfibril glycoprotein, fibrillin.
c. Clinical findings include tall stature, joints that can be hyperextended, and cardiovascular defects, including mitral valve prolapse and dilation of the ascending aorta.
Ehlers-Danlos syndrome
a. Genetic transmission: autosomal dominant or recessive.
b. This group of diseases is characterized by defects in collagen.
c. Clinical findings include hypermobile joints and highly stretchable skin. The skin also bruises easily. Oral findings include Gorlin’s sign and possible temporomandibular joint (TMJ) subluxation.
The oral mucosa may also appear more fragile and vulnerable to trauma.
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