NEET MDS Lessons
General Pathology
Human immunodeficiency virus (HIV)
1. Part of the Retroviridae family (i.e., it is a retrovirus).
2. Basic virion structure
a. The nucleocapsid contains single stranded RNA and three enzymes: reverse transcriptase, integrase, and protease.
b. An exterior consists of two glycoproteins, gp120 and gp41, which are imbedded in the lipid bilayer. This lipid bilayer was obtained from the host cell via budding.
3. Virion characteristics
a. The HIV genome includes:
(1) gag gene—codes for core proteins.
(2) pol gene—codes for its three enzymes.
(3) env gene—codes for its two envelope glycoproteins.
b. HIV enzymes
(1) Reverse transcriptase—reverse transcription of RNA to viral DNA.
(2) Integrase—responsible for integrating viral DNA into host DNA.
(3) Protease—responsible for cleaving precursor proteins.
4. Pathogenicity
a. HIV mainly infects CD4 lymphocytes, or helper T cells. Its envelope protein, gp120, binds specifically with CD4 surface
receptors. After entry, viral RNA is transcribed by reverse transcriptase to viral DNA and integrated into the host DNA. New virions are synthesized and released by lysis of the host cell.
b. The predominant site of HIV replication is lymphoid tissues.
c. Although HIV mainly infects CD4 helper T cells, it can bind to any cell with a CD4 receptor, including macrophages, monocytes, lymph node dendritic cells, and a selected number of nerve cells. Macrophages are the first cells infected by HIV.
5. HIV infection versus acquired immunodeficiency syndrome (AIDS).
a. AIDS describes an HIV-infected person who has one of the following conditions:
(1) A CD4 lymphocyte count of less than 200.
(2) The person is infected with an opportunistic infection or other AIDS-defining illness, including (but not limited to) tuberculosis, recurrent pneumonia infections, or invasive cervical cancer.
b. The cause of death in an AIDS patient is most likely due to an opportunistic infection.
6. Common opportunistic infections associated with AIDS:
a. Pneumonia caused by Pneumocystis jiroveci (carinii).
b. Tuberculosis.
c. Periodontal disease—severe gingivitis, periodontitis, ANUG, necrotizing stomatitis.
d. Candidiasis.
e. Oral hairy leukoplakia (EBV).
f. Kaposi’s sarcoma (HHV-8).
g. Recurrent VZV infections.
h. Condyloma acuminatum or verruca vulgaris (warts, HPV)—less common.
i. CMV infections.
j. Disseminated herpes simplex, herpes zoster.
k. Hodgkin’s, non-Hodgkin’s lymphoma.
7. Laboratory diagnosis of HIV
a. ELISA test—detects HIV antibodies.
False negatives do occur.
b. Western blot—detects HIV proteins.
There is a 99% accuracy rate when both the ELISA test and Western blot are used to diagnose HIV infection.
c. PCR—more sensitive; can amplify and identify the virus at an early stage.
8. Treatment
a. Inhibitors of reverse transcriptase.
(1) Nucleoside analogs
(a) Inhibit viral replication via competitive inhibition.
(b) Examples: zidovudine (AZT), didanosine, lami- vudine, stavudine.
(2) Nonnucleoside inhibitors.
(a) Act by binding directly to reverse transcriptase.
(b) Examples: nevirapine, delavirdine.
b. Protease inhibitor.
c. “Triple cocktail” therapy—often consists of two nucleoside inhibitors and a protease inhibitor.
Respiratory Pathology
A. Pulmonary infections
1. Bacterial pneumonia
a. Is an inflammatory process of infectious origin affecting the pulmonary parenchyma.
2. Bacterial infections include:
a. Streptococcus pneumoniae (most common).
b. Staphylococcus aureus.
c. Haemophilus influenzae.
d. Klebsiella pneumoniae.
e. Anaerobic bacteria from the mouth
(aspiration of oral secretions).
3. Viral infections include:
a. Influenza.
b. Parainfluenza.
c. Adenoviruses.
d. Respiratory syncytial virus.
Note: viruses can also cause pneumonia. Infection of the interstitial tissues, or interstitial pneumonia, is commonly associated with these types of infections.
Common symptoms include fever, dyspnea, and a productive cough
Two types:
(1) Lobar pneumonia
(a) Infection may spread through entire lobe(s) of lung. Intraalveolar exudates result in dense consolidations.
(b) Typical of S. pneumoniae infections.
(2) Bronchopneumonia
(a) Infection and inflammation spread through distal airways, extending from the bronchioles and alveoli. A patch distribution involving one or more lobes is observed.
(b) Typical of S. aureus, H. influenzae,and K.pneumoniae infection
Diseases that Produce a Productive Cough
Pneumonia
Lung abscess
Tuberculosis
Chronic bronchitis
Bronchiectasis
Bronchogenic carcinoma
Classification
Diseases of the respiratory system can be classified into four general areas:
- Obstructive Diseases (e.g., Emphysema, Bronchitis, Asthma)
- Restrictive Diseases (e.g., Fibrosis, Sarcoidosis, Alveolar Damage, Pleural Effusion)
- Vascular Diseases (e.g., Pulmonary Edema, Pulmonary Embolism, Pulmonary Hypertension)
- Infectious, Environmental and Other Diseases (e.g., Pneumonia, Tuberculosis, Asbestosis, Particulate Pollutants)
EMBOLISM
Definition: transportation of an abnormal mass of an abnormal mass of undissolved material from one part of circulation to another. The mass transported is called embolus.
Types
I .Thrombi and clots.
2. Gas or air.
3. Fat
4.Amniotic fluid.
5.Tumour
Thromboembolism
This is the commonest type of embolus and may be formed of the primary thrombus or more often of propagated clot region which is loosely attached.
Emboli from venous thrombi can result In impaction in the pulmonary arteries and result in sudden death.
Embolism from cardiac or arterial thrombi results in systemic embolism causing infraction and gangrene.
Gaseous
This occurs when gas is introduced into the circulation:
• Accidental opening of large veins during surgery.
• Mismanaged transfusion. .
As air is readily absorbed into blood only sudden introduction or large quantities of air produces effects
Caisson’s Disease bubbling of nitrogen from the blood during sudden decompression as seen during deep sea diving.
Fat Embolism
Causes
• Fractures especially of long bones and multiple
• Crush injuries.
Sites of impaction:
o Lungs.
o Systemic: causing -
→ petechial skin haemorrhages.
→ Embolism to brain leading to coma and death.
→ Conjunctival and retinal haemorrhages
Tumor Embolism.
Invasion of vascular channe1.s is a feature of malignant neoplasms and this leads to:
• Metastatic deposits,
• DlC
Causes of disease
The causes of disease Diseases can be caused by either environmental factors, genetic factors or a combination of the two.
A. Environmental factors
Environmental causes of disease are many and are classified into:
1. Physical agents
2. Chemicals
3. Nutritional deficiencies & excesses
4. Infections & infestations
5. Immunological factors
6. Psychogenic factors
1. Physical agents
These include trauma, radiation, extremes of temperature, and electric power. These agents
apply excess physical energy, in any form, to the body.
2. Chemicals
With the use of an ever-increasing number of chemical agents such as drugs,
3. Nutritional deficiencies and excesses
Nutritional deficiencies may arise as a result of poor supply, interference with absorption, inefficient transport within the body, or defective utilization. It may take the form of deficiency.
4. Infections and infestations
Viruses, bacteria, fungi, protozoa, and metazoa all cause diseases. They may do so by causing cell destruction directly as in virus infections (for example poliomyelitis) or protozoal infections (for example malaria).
5. Immunological factors
A. Hypersensitivity reaction
This is exaggerated immune response to an antigen. For example, bronchial asthma can occur due to exaggerated immune response to the harmless pollen.
B. Immunodeficiency
This is due to deficiency of a component of the immune system which leads to increased susceptibility to different diseases. An example is AIDS.
C. Autoimmunity
This is an abnormal (exaggerated) immune reaction against the self antigens of the host. Therefore, autoimmunity is a hypersensitivity reaction against the self antigens. 4
6. Psychogenic factors
The mental stresses imposed by conditions of life, particularly in technologically advanced
communities, are probably contributory factors in some groups of diseases.
B. Genetic Factors
These are hereditary factors that are inherited genetically from parents.
Chemical Mediators In Inflammation
Can be classified as :
A. Neurogenic
Also called the Triple Response of Lewis. It involves neurogenic vasodilatation of arterioles due to antidromic axon reflex arc. The constituents of the response are:
1. arteriolar vasoconstriction followed by
2. arteriolar vasodilatation
3. swelling
B. Chemical
1. Amines: Histamine and 5 hydroxytryptamine. Released from platelets and mast cells.
Actions: Immediate and short lived.
Dilatation of arterioles.
Increased capillary premeability.
Kinins: Bradykinin and kallidin These are present in inactive from and are activated by kinin forming proteases
Actions:
Arteriolar dilatation.
Increased vascular permeability
Pain
Kinin forming proteases Plasmin and Kallikrein. Present as inactive precursors.
Cleavage products of complement C3a und C5a are called anaphylatoxins
Actions:
Histamine release from mast cells
Chemotaxis (also C567 )
Enhance phagocytosis.
Polymorph components
Cationic: proteins which cause
Increased permeability
Histamine release.
Chemotaxis of monocytes
Neutral proteases which:
Cleave C3 and C5 to active form
Convert Kininogen to Kinin
Increase permeability.
Acid proteases which liberate leucokinins
Slow reacting. substance of anaphylaxis: (SRS-A) is a lipid released from mast cell.
Action --Increases vascular permeability
Prostaglandins: E1 + E2 .
Platelets are rich source
Action:
Platelets are a rich source.
Vasodilatation.
Increased permeability.
Pain.
VIII. Miscellaneous: like
Tissue lactic acid.
Bacterial toxins.
Infectious Mononucleosis
It is an Epstein Barr virus infection in children and young adults.
Features
-Constitutional symptoms.
-Sore throat.
-Lymphnode enlargement.
-Skin rashes
-Jaundice.
-Rarely pneumonia, meningitis and encephalitis.
Blood Picture
- Total count of I0,000. 20,000 /cu.mm.
- Lymphocytosis (50-90%) with atypical forms. They are larger with more cytoplasm which may be vacuolated or basophilic. Nucleus may be indented. with nucleoli (Downy type I to III).
- Platelets may be reduced.
- Paul Bunell test (for heterophil antibody against sheep RBC) is positive
Surface Defence Mechanisms
1. Skin:
(i) Mechanical barrier of keratin and desquamation.
(ii) Resident commensal organisms
(iii)Acidity of sweat.
(iv) Unsaturated fatty acids of sebum
2. Oropharyngeal
(i)Resident flora
(ii) Saliva, rich in lysozyme, mucin and Immunoglobulins (lgA).
3. Gastrointestinal tract.-
(i) Gastric HCI
(ii) Commensal organisms in Intestine
(iii) Bile salts
(iv) IgA.
(v) Diarrhoeal expulsion of irritants.
4. Respiratory tract:
(i) Trapping in turbinates
(ii) Mucus trapping
(iii) Expulsion by coughing and sneezing.
(iv) Ciliary propulsion.
(V) Lysozymes and antibodies in secretion.
(vi) Phagocytosis by alveolar macrophages.
5. Urinary tract:
(i) Flushing action.
(ii) Acidity
(iii) Phagocytosis by urothelial cells.
6. Vagina.-
(i) Desquamation.
(ii) Acid barrier.
(iii) Doderlein's bacilli (Lactobacilli)
7. Conjunctiva:
Lysozymes and IgA in tears