NEET MDS Lessons
General Pathology
EXOCRINE PANCREAS
Congenital anomalies
1. Ectopic pancreatic tissue most commonly occurs in the stomach, duodenum, jejunum, Meckel's diverticulum, and ileum. It may be either asymptomatic or cause obstruction, bleeding, intussusception.
2.Annular pancreas is a ring of pancreatic tissue that encircle the duodenum and may cause duodenal obstruction.
Cystic fibrosis
Cystic fibrosis is a systemic disorder of exocrine gland secretion presenting during infancy or childhood.
Incidence is 1:2500 in Caucasians; it is less common in Black and extremely rare in Asians.
Pathogenesis. Cystic fibrosis shows autosomal recessive transmission; heterozygotes are unaffected. It results in a defective chloride channel, which leads to secretion of very thick mucus.
Characteristics
- Tissues other than exocrine glands are normal, and glands are structurally normal until damaged by cystic fibrosis.
- The only characteristic biochemical abnormalities are an elevation of sodium and chloride levels in sweat, and a decrease in water and bicarbonate secretion from pancreatic cells, resulting in a viscous secretion.
Clinical features
- Fifteen percent of cases present with meconium ileus.
- Most cases present during the first year with steatorrhea (with resultant deficiencies of vitamins A, D, E, and K), abdominal distention, and failure to thrive.
Complications are also related to pulmonary infections'and obstructive pulmonary disease as a result of viscous bronchial secretions.
Pathology
- There is mucus plugging of the pancreatic ducts with cystic dilatation, fibrous proliferation, and atrophy. Similar pathology develops in salivary glands.
- Lungs. Mucus impaction leads to bronchiolar dilatation an secondary infection.
- The gastrointestinal tract shows obstruction caused mucus impaction in the intestines with areas of biliary cirrhosis, resulting from intrahepatic bile duct obstruction
Diagnosis depends on demonstrating a "sweat test" abnomality associated with at least one clinical feature In sweat test, high levels of chloride are demonstrated.
Prognosis. Mean survival is age 20; mortality is most often due to pulmonary infections.
Degenerative changes
1. Iron pigmentation (e.g., from hemochromatosis) may be deposited within acinar and islet cells and may cause insulin deficiency.
2. Atrophy
a. Ischemic atrophy is due to atherosclerosis of pancreatic arteries and is usually asymptomatic.
b. Obstruction of pancreatic ducts affects only the exocrine pancreas, which becomes small, fibrous, and nodular.
Acute hemorrhagic pancreatitis
presents as a diffuse necrosis of the pancreas caused by the release of activated pancreatic
enzymes. Associated findings include fat necrosis and hemorrhage into the pancreas.
Incidence. This disorder is most often associated with alcoholism and biliary tract disease.
It affects middle-aged individuals and often occurs after a large meal or excessive alcohol ingestion; approximately 50% of patients have gallstones.
Pathogenesis. There are four theories.
- Obstruction of the pancreatic duct causes an elevated intraductal pressure, which results in leakage of enzymes from small ducts.
- obstruction may be caused by a gallstone at the ampulla of Vater; chronic alcohol ingestion may cause duct obstruction by edema.
- Hypercalcemia may cause activation of trypsinogen; its mechanism is unclear. Pancreatitis occurs in 20% of patients with hyperparathyroidism.
- Direct damage to acinar cells may occur by trauma, ischemia, viruses, and drugs.
- Hyperlipidemia may occur as a result of exogenous estrogen intake and alcohol ingestion.
Clinical features are typically the sudden onset of acute, continuous, and intense abdominal pain, often radiating to the back and accompanied by nausea, vomiting, and fever. This syndrome frequently results in shock.
Laboratory values reveal elevated amylase (lipase elevated after 3-4 days) and leukocytosis. Hypocalcemia is a poor prognostic sign.
Chronic pancreatitis
It refers to remitting and relapsing episodes of mild pancreatitis, causing progressive pancreatic damage.
Incidence is similar to acute pancreatitis. It is also seen in patients with ductal anomalies. Almost half the cases occur without known risk factors.
Pathogenesis is unclear; possibly, there is excess protein secretion by the pancreas, causing ductal obstruction.
Clinical features include flareups precipitated by alcohol and overeating, and drugs. Attacks are characterized by upper abdominal pain, tenderness, fever, and jaundice.
Laboratory values reveal elevated amylase and alkaline phosphatase, X-rays reveal calcifications in the pancreas. Chronic pancreatitis may result in pseudocyst formation, diabetes, and steatorrhea.
Carcinoma of the pancreas
Incidence:
Carcinoma of the pancreas accounts for approximately 5% of all cancer deaths. Increased risk is associated with smoking. high-fat diet, and chemical exposure. There is a higher incidence in the elderly, Blacks, males, and diabetics.
Clinical features
- The disease is usually asymptomatic until late in its course.
- Manifestations include weight loss, abdominal pain frequently radiating to the back, weakness, malaise, anorexia, depression, and ascites.
- There is jaundice in half of the patients who have carcinoma of the head of the pancreas.
- Courvoisier's law holds that painless jaundice with a palpable gallbladder is suggestive of pancreatic cancer.
Pathology
Carcinomas arise in ductal epithelium. Most are adenocarcinomas.
- Carcinoma of the head of the pancreas accounts for 60% of all pancreatic cancers.
- Carcinoma of the body (20%) and tail (5%) produce large indurated masses that spread widely to the liver and lymph nodes.
- In 15% of patients, carcinoma involves the pancreas diffusely.
Complications
include Trousseau's syndrome, a migratory thrombophlebitis that occurs in 10% of patients.
Prognosis is very poor. if resectable, the 5-year survival rate less than 5%. The usual course is rapid decline; on average death occurs 6 months after the onset of symptoms.
Diagnostic techniques used in pathology
The pathologist uses the following techniques to the diagnose diseases:
a. Histopathology
b. Cytopathology
c. Hematopathology
d. Immunohistochemistry
e. Microbiological examination
f. Biochemical examination
g. Cytogenetics
h. Molecular techniques
i. Autopsy
ATROPHY
It is the acquired decrease in the size of an organ due to decrease in the size and/or number of its constituent cells.
Causes:
(1) Physiological
- Foetal involution.
o Branchial clefts.
o Ductus arterious.
- Involution of thymus and other lymphoid organs in childhood and adolescence.
- In adults:
o Post-partum uterus.
o Post-menopausal ovaries and uterus
o Post-lactational breast
o Thymus.
(2) Pathological:
- Generalised as in
o Ageing.
o Severe starvation and cachexia
- Localised :
o Disuse atropy of bone and muscle.
o Ischaemic atrophy as in arteriosclerotic kidney. .
o Pressure atrophy due to tumours and of kidney in hydronephrosis.
o Lack of trophic stimulus to endocrines and gonads.
Pulmonary Hypertension
Sustained elevation of mean pulmonary arterial pressure.
Pathogenesis
Elevated pressure, through endothelial cell dysfunction, produces structural changes in the pulmonary vasculature. These changes ultimately decrease pulmonary blood flow and stress the heart to the point of failure. Based on etiology, pulmonary hypertension is divided into two categories.
Primary (idiopathic): The cause is unknown.
Secondary: The hypertension is secondary to a variety of conditions which increase pulmonary blood flow or increase resistance to blood flow. Example: Interstitial fibrosis.
Pathology
The changes involve large and small pulmonary blood vessels and range from mild to severe. The major changes include atherosclerosis, striking medial hypertrophy and intimal fibrosis of small arteries and arterioles, and plexogenic arteriopathy. Refer to Figure 15-7 in your textbook.
Pathophysiology
Dyspnea and fatigue eventually give way to irreversible respiratory insufficiency, cyanosis and cor pulmonale.
1. Pyogenic liver abscesses may be caused by E. coli, Klebsiella, Streptococcus, Staphylococcus, Bacteroides, Pseudomonas, and fungi.
Parasitic infections
1. Schistosomiasis is caused by different organisms in different parts of the world.
a. Clinical features include splenomegaly, portal hypertension, and ascites. Lesions are caused by the immune response to ova.
2. Amebiasis is caused by Entamoeba histolytica.
a. Clinical features include bloody diarrhea, pain, fever, jaundice, and hepatomegaly.
Drug-induced liver damage may be caused by agents that are direct hepatotoxins, such as carbon tetrachloride, acetaminophen, methotrexate, anabolic steroids, and oral contraceptive pills.
IMMUNO PATHOLOGY
Abnormalities of immune reactions are of 3 main groups
- Hypersensitivity,
- Immuno deficiency,
- Auto immunity.
Hypersensitivity (ALLERGY)
This is an exaggerated or altered immune response resulting in adverse effects
They are classified into 4 main types.
I. Type I-(reaginic, anaphylactic). This is mediated by cytophylic Ig E antibodies, which get bound to mast cells. On re-exposure, the Ag-Ab reaction occurs on the mast cell surface releasing histamine.
Clinical situations
I. Systemic anaphylaxis, presenting with bronchospasm oedema hypertension, and even death.
2. Local (atopic) allergy.
- Allergic rhinitis (hay fever)
- Asthma
- Urticaria.
- Food allergies.
2. Type II. (cytotoxic). Antibody combines with antigen present on-cell surface. The antigen may be naturally present on the surface or an extrinsic substance (e.g.drug) attached to cell surface.
The cell is then destroyed by complement mediated lysis (C89) or phagocytosis of the antibody coated cell.
Clinical situations
- Haemolytic anemia.
- Transfusion reaction
- Auto immune haemolytic anemia.
- Haemolysis due to some drugs like Alpha methyl dopa
Drug induced thrombocytopenia (especially sedormid).
Agranulocytosis due to sensitivity to some drugs.
Goodpasture’s syndrome-glomermerulonephritis due to anti basement membrane antibodies.
3. Type III. (Immune complex disease). Circulating immune complexes especially
small soluble complexes tend to deposit in tissues especially kidney, joints, heart and
arteries.
These then cause clumping of platelets with subsequent release of histamine. and
serotonin resulting in increased permeability. Also, complement activation occurs which
being chemotactic results in aggregation of polymorphs and necrotising vasculitis due to
release of lysosmal enzymes
Clinical situations
- Serum sickness.
- Immune complex glomerulonephritis.
- Systemic lupus erythematosus.
- Allergic alveolitis.
- Immune based vasculitis like
- Drug induced vasculitis.
- Henoch – Schonlein purpura
4. Type IV. (Cell mediated). The sensitized lymphocytes may cause damage by
cytotoxicity or by lymphokines and secondarily involving macrophages in the reaction.
Clinical situations
I. Caseation necrosis in tuberculosis.
2. Contact dermatitis to
- Metals.
- Rubber.
- Drugs (topical).
- Dinitrochlorbenzene (DNCB).
5. Type V. (stimulatory) This is classed by some workers separately and by other with
cytotoxic type (Type II) with a stimulatory instead of toxic effect
Clinical Situations :
LATS (long acting thyroid stimulator) results in thyrotoxicosis (Grave’s disease)
HYPERTENSIVE VASCULAR DISEASE
Malignant hypertension
A small percentage of HTN patients (5%) present with a rapidly rising blood pressure that, if untreated, leads to death within 1 to 2 years.
systolic pressures -> 200 mm Hg or diastolic pressures -> 120 mm Hg
Associated with renal failure and retinal hemorrhages
Most commonly is superimposed on preexisting benign hypertension
Hypertension (HTN) has the following complications
- stroke (CVD)
- multi-infarct dementia
- atherosclerotic coronary heart disease
- cardiac hypertrophy and heart failure (hypertensive heart disease)
- aortic dissection
- renal failure
Essential HTN Accounts for 90% to 95% of all cases
SecondaryHTN
Renal - > Acute glomerulonephritis Chronic renal disease
Endocrine - > Cushing syndrome, Hypothyroidism (myxedema) Hyperthyroidism (thyrotoxicosis) Pregnancy-induced (pre-eclampsia)
Cardiovascular - > Coarctation of aorta
Neurologic
Psychogenic, Increased intracranial pressure
PATHOGENESIS
most cases (95%) are idiopathic (essential hypertension)
Most of the remaining cases (secondary hypertension) are due to primary renal disease, renal artery narrowing
Gene defects in enzymes involved in aldosterone metabolism
Mutations in proteins that affect sodium resorption as in Liddle syndrome
Genetic factors - > familial clustering of hypertension
Environmental factors such as stress, obesity, smoking, physical inactivity, and high levels of salt consumption, modify the impact of genetic determinants
Morphology
HTN is associated with arteriolosclerosis (small arterial disease)
Two forms of small blood vessel disease are hypertension-related:
1- hyaline arteriolosclerosis
2- hyperplastic arteriolosclerosis
Hyaline arteriolosclerosis
Associated with benign hypertension.
-marked by homogeneous, pink hyaline thickening of the arteriolar walls, and luminal narrowing.
Hyperplastic arteriolosclerosis
It is more typical of severe hypertension.
- "onionskin," concentric, laminated thickening of arteriolar walls and luminal narrowing.
- The laminations consist of smooth muscle cells and thickened, reduplicated basement membrane.
DISORDERS OF BLOOD VESSEL HYPERREACTIVITY
Several disorders are characterized by inappropriate or exaggerated vasoconstriction of blood vessels:
1- Raynaud Phenomenon
2- Myocardial Vessel Vasospasm
Raynaud Phenomenon
- results from exaggerated vasoconstriction of arteries and arterioles in the extremities (the fingers and toes, but also sometimes the nose, earlobes, or lips).
-restricted blood flow induces paroxysmal pallor or cyanosis
- involved digits characteristically show "red-white-andblue" color changes from most proximal to most distal
Myocardial Vessel Vasospasm
Causes: 1- vasoactive mediators - > prolonged vascular contraction;
- endogenous (e.g., epinephrine released by pheochromocytomas) or exogenous (cocaine or phenylephrine).
2- Elevated thyroid hormone -> increase sensitivity of vessels to catecholamines
3- autoantibodies and T cells in scleroderma vascular instability and vasospasm.
4- extreme psychological stress (release of catecholamines)
Cardiac raynaud
When vasospasm of cardiac arterial or arteriolar bed is of sufficient duration (20 to 30 min ) myocardial infarction occurs
acute microscopic area of necrosis characterized by mycotic hypercontraction (contraction band necrosis)
subacute and chronic cases - > microscopic foci of granulation tissue or scar