Molecular techniques

Different molecular techniques such as fluorescent in situ hybridization, Southern blot, etc... can be used to detect genetic diseases.

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

Iron deficiency anaemia.

Absorption of iron is affected by :
- Iron stores.
- Rate of erythropoiesis
- Acid pH aids absorption.
- Phosphates and phytates in diet impair absorption.

Causes  of deficiency:

- Increased demand:
o    Growth (in children)
o    Menstruation, Pregnancy, lactation.
- Inadequate intake and absorption.
o    Dietary deficiency.
o    Achlorhydria or gastrectomy.
o    Malabsorption states.

- Chronic blood loss
o    Peptic ulcer, bleeding piles
o    Menorrhagia.
o    Hook worm infestation

Features:
- Anaemia.
- Koilonychia.
- Atrophic glossitis and angular stomatitis.
- Dysphagia-Plummer Vinson syndrome.

Blood findings:

- Microcytjc_hypochromic cells, ring cells and pessary cells.
- Anisocytosis and poikilocytosis.
- Low MCV. MCH and MCHC.
- Serum iron is low but iron binding capacity is increased

Bone marrow

Erythroid hyperplasia with imcronormoblasts. Iron stains reveal depleted stores

Differential  diagnosis .-

- Sideroblastic anaemia which is also microcytic hypochromic  but there is excess iron in the erythroid cells .Some are pyridoxine responsive.
- (ii) Thalassaemia
 

Alzheimer’s disease
a. The most common cause of dementia in older people.
b. Characterized by degeneration of neurons in the cerebral cortex.
c. Histologic findings include amyloid plaques and neurofibrillary tangles.
d. Clinically, the disease takes years to develop and results in the loss of cognition, memory, and the ability to ommunicate. Motor problems, contractures, and paralysis are some of the symptoms at the terminal stage.

Haemolysis due to drugs and chemicals

This can be caused by :

1. Direct toxic action.
    -> Naphthalene.
    -> Nitrobenzene.
    -> Phenacetin.
    -> Lead.

Heinz bodies are seen in abundance.

2. Drug action on G-6-PD deficient RBC
3. Immunological mechanism which may be : 
    -> Drug induced  autoantibody haemolysis, Antibodies are directed against RBC.
    -> Hapten-cell mechanism where antibodies are directed against which is bound to cell surface e.g. Penicilin.
 

Lymphopenia:
Causes

-As part of pancytopenia.
-Steroid administration.