NEET MDS Lessons
General Pathology
Posterior Pituitary Syndromes
The posterior pituitary, or neurohypophysis, is composed of modified glial cells (termed pituicytes) and axonal processes extending from nerve cell bodies in the hypothalamus. The hypothalamic neurons produce two peptides: antidiuretic hormone (ADH) and oxytocin that are stored in axon terminals in the neurohypophysis.
The clinically important posterior pituitary syndromes involve ADH production and include
1. Diabetes insipidus and
2. Inappropriate secretion of high levels of ADH.
- ADH is released into the general circulation in response to increased plasma oncotic pressure & left atrial distention.
- It acts on the renal collecting tubules to increase the resorption of free water.
- ADH deficiency causes diabetes insipidus, a condition characterized by polyuria. If the cause is related to ADH Diabetes insipidus from - - ADH deficiency is designated as central, to differentiate it from nephrogenic diabetes insipidus due to renal tubular unresponsiveness to circulating ADH.
- The clinical manifestations of both diseases are similar and include the excretion of large volumes of dilute urine with low specific gravity. Serum sodium and osmolality are increased as a result of excessive renal loss of free water, resulting in thirst and polydipsia.
- ADH excess causes resorption of excessive amounts of free water, with resultant hyponatremia.
- The most common causes of the syndrome include the secretion of ectopic ADH by malignant neoplasms (particularly small-cell carcinomas of the lung), and local injury to the hypothalamus and/or neurohypophysis.
- The clinical manifestations are dominated by hyponatremia, cerebral edema, and resultant neurologic dysfunction.
FUNGAL INFECTION
Aspergillosis
Opportunistic infections caused by Aspergillus sp and inhaled as mold conidia, leading to hyphal growth and invasion of blood vessels, hemorrhagic necrosis, infarction, and potential dissemination to other sites in susceptible patients.
Symptoms and Signs: Noninvasive or, rarely, minimally locally invasive colonization of preexisting cavitary pulmonary lesions also may occur in the form of fungus ball (aspergilloma) formation or chronic progressive aspergillosis.
Primary superficial invasive aspergillosis is uncommon but may occur in burns, beneath occlusive dressings, after corneal trauma (keratitis), or in the sinuses, nose, or ear canal.
Invasive pulmonary aspergillosis usually extends rapidly, causing progressive, ultimately fatal respiratory failure unless treated promptly and aggressively. A. fumigatus is the most common causative species.
Extrapulmonary disseminated aspergillosis may involve the liver, kidneys, brain, or other tissues and is usually fatal. Primary invasive aspergillosis may also begin as an invasive sinusitis, usually caused by A. flavus, presenting as fever with rhinitis and headache
Liver cirrhosis
It is a chronic, progressive diffuse process characterized by
a. Hepatocellular necrosis
b. Replacement by fibrosis and inflammation
c. Hyperplasia of surviving liver cells forming regenerating nodules
d. Vascular derangement.
All these changes lead to loss of the normal liver architecture.
Pathology of cirrhosis
At first the liver is enlarged or of normal size. Late in the disease, it is reduced in size and weight.
Consistency- Firm.
Colour -May be yellow (fatty change), red (congestion), green (cholestaisis), or pale gray (recent nodules due to absence of pigment).
Morphologically According to the size of these nodules, cirrhosis can be classified
Micronodular (regular) cirrhosis. Small nodules 2-3 mm.in diameter.
Macronodular (irregular) cirrhosis, nodules up to one cm in diameter.
Mixed cirrhosis is the end stage of all types of cirrhosis
Microscopic picture
1 Regenerating nodulesn- Proliferated hepatocytes arranged in thick plates and separated by blood sinusoids. Central vein in abnormal sites (eccentric) - Hepatocytes may be small , large , or binucleated
2- Fibrosis- It replaces damaged hepatocytes. It develops at certain sites:-
a-perivenular b -perisinusoidal c -pericellular and d -in relation to portal tracts.
- It may be young, cellular and highly vascular or mature with diminished vasculsarity. It encloses groups of hepatocytes, lobules or regenerating nodules.
-As a result of hepatocyte injury and fibrosis, there’s loss of normal liver architecture including the lobular and acinar pattern as well as the liver cell plates
3- Bile ductular proliferation:- Occurs in the fibrous septa.Focal choestaisis with feathery degeneration of hepatocytes occur at the margins of regenerating nodules. It becomes diffuse terminally.
4- Inflammatory cells:- Lymphocytes, macrophages and plasma cells infiltrate the fibrous septa and regenerating nodules
Etiological classification of cirrhosis
Congenital Occurs at childhood
- congenital syphilis
Hereditary diseases:-
a. Primary idiopathic haemochromatosis b. Thalassemia c. Wilson’s disease d.α 1-antitrypsin deficien e. glycogen storage disease
Acquired
-Cryptogenic (10-50%).
-Alcoholic (30-70%)
-Post viral (15-20%)
- Biliary cirrhosis (16%) primary or secondary.
Huntington’s disease
a. Causes dementia.
b. Genetic transmission: autosomal dominant.
c. Characterized by the degeneration of striatal neurons, affecting cortical and basal ganglia function.
d. Clinically, the disease affects both movement and cognition and is ultimately fatal.
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
Myocardial infarction (MI)—heart attack
A. Ischemia versus MI: Ischemia is a reversible mismatch between the supply and demand of oxygen. Infarction
is an irreversible mismatch that results in cell death caused by the lack of blood flow (oxygenation). For instance, chest pain caused by ischemia can be relieved by administering nitroglycerin (a vasodilator) to the patient. If the patient has an MI, the pain will not be relieved with nitroglycerin.
1. MIs most commonly occur when a coronary artery is occluded by a thrombus generated in an atherosclerotic artery.
2. Symptoms include:
a. Chest pain, shortness of breath.
b. Diaphoresis (sweating), clammy hands.
c. Nausea, vomiting.
3. Consequences:
a. Death (one third of patients).
b. Arrhythmias (most common immediate cause of death).
c. Congestive heart failure.
d. Myocardial rupture, which may result in death from cardiac tamponade.
e. Thrombus formation on infarcted tissue; may result in systemic embolism.
Enterococci
Most common are E. fecalis and E. fecium. Cause inflammation at site of colonization.
Serious resistance to antibiotics. E. fecium is now a vancomycin resistant enterococcus (VRE)