HERPES ZOSTER (Shingles)

An infection with varicella-zoster virus primarily involving the dorsal root ganglia and characterized by vesicular eruption and neuralgic pain in the dermatome of the affected root ganglia.

caused by varicella-zoster virus

Symptoms and Signs

Pain along the site of the future eruption usually precedes the rash by 2 to 3 days. Characteristic crops of vesicles on an erythematous base then appear, following the cutaneous distribution of one or more adjacent dermatomes

Eruptions occur most often in the thoracic or lumbar region and are unilateral. Lesions usually continue to form for about 3 to 5 days

Geniculate zoster (Ramsay Hunt's syndrome) results from involvement of the geniculate ganglion. Pain in the ear and facial paralysis occur on the involved side. A vesicular eruption occurs in the external auditory canal, and taste may be lost in the anterior two thirds of the tongue

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.

Nonspecific or Innate Immunity

1. Genetic factors

• Species: Guinea pig is very susceptible to tuberculosis.
• Race: Negroes are more susceptible to tuberculosis than whites
• Sickle cells (HbS-a genetic determined Haemoglobinopathy resistant to Malarial parasite.

2. Age Extremes of age are more susceptible.

3. Hormonal status. Low resistance in:

• Diabetes Mellitus.
• Increased corticosteroid levels.
• Hypothyroidism

4. Phagocytosis. Infections can Occur in :

• Qualitative  or quantitative defects in neutrophils and monocytes.
• Diseases of mononuclear phagocytic system (Reticuloendothelial cells-RES).
• Overload blockade of RES.

5. Humoral factors

• Lysozyme.
• Opsonins.
• Complement
• Interferon (antiviral agent secreted by cells infected by virus)

Thrombosis

Definition-The formation from constituents of the blood, of a mass within the venous or arterial vasculature of a living animal. Natural defense of the body to acute vascular injury.

Pathologic thrombosis includes deep venous thrombosis (DVT), pulmonary embolism (PE), coronary artery thrombosis leading to myocardial infarct and cerebrovascular thrombosis leading to stroke.

Coagulated blood- clots formed 

Clot – formation of solid mass of blood components formed outside the vascular tree
Thrombosis with resulting embolic phenomena is important cause of morbidity and mortality.

Haemostatic system allows blood to remain in fluid form under normal conditions and causes the development of temporary thrombus at site of vascular injury.

Components of haemostatic system:
1.    Platelets
2.    Vascular endothelium
3.    Procoagulant plasma protein clotting factors
4.    Natural anticoagulants
5.    Fibrinolytic proteins
6.    Antifibrinolytic proteins

Normal haemostasis:
1.    Primary haemostasis-platelet plug formation
2.    Secondary haemostasis-stable plug or thrombus
3.    Natural anticoagulants-confines thrombus site and size to maintain blood flow
4.    Fibrinolysis-degrades fibrin , limits thrombus size and dissolves thrombus once vessel injury is repaired

Changes in any of these factors may result in pathologic thrombosis.

Pathophysiology of thrombosis:
Virchow’s Triad-Thrombosis results from a) decreased blood flow b) vascular endothelial injury and c) alterations in the components of blood.

Vessel wall:
EC (intima), smooth muscle cells (media) and the connective tissue (adventitia).Vascular endothelium is thromboresistant. EC injury leads to TF expression and thrombosis.
Vessel wall has antiplatelet, anticoagulant and fibrinolytic activities which make it thromboresistant.
Antiplatelet activities:
1.    Prostacyclin synthesized by EC in response to thrombin. Inhibits platelet adhesion as well as causes vasodilation
2.    NO regulates vascular tone as well as functioning as inhibitor of platelet adhesion. Constitutive expression as well as induced expression by EC in response to cytokines
3.    Ectozymes which metabolize ADP and ATP to AMP and adenosine. Adenosine inhibits platelet function, ADP is platelet agonist

Anticoagulant activities:
1.    Synthesis of heparin like GAG which inactivate activated clotting factors
2.    Protein C and S and thrombomodulin-Thrombin generated binds to thrombomodulin which activates protein C which then binds to Protein S and this inhibits coagulation by its proteolytic effect on Factors Va and VIIIa
3.    TFPI is synthesized by EC and  regulates TF-VIIa activation of Factor X. Also inhibits vascular cell proliferation

Fibrinolytic activities:
1.    Secretion and synthesis of plasminogen activators TPA in response to thrombin and vasoactive stimulants such as vasopressin and histamine
2.    Synthesis of urokinase in response to inflammatory cytokines
3.    FDP’s generated have antiplatelet and antithrombin activity
4.    Secretion of PAI

Prothrombotic properties of vascular endothelium promote coagulation with appropriates stimuli.

EC exposure to stimuli such as trauma, cytokines, atherogenic stimuli, endotoxins and immune complexes result in increased TF expression, reduced Protein C activation and reduced fibrinolysis so converting an antithrombotic surface to a prothrombotic surface.
Inherited conditions which result in abnormalities of EC derived or regulated proteins will cause thrombosis.

Arterial thrombosis:
1.    Abnormal vessel wall due to atherosclerotic plaque rupture, arterial outflow obstruction, vessel dissection EC injury promote platelet adhesion and activation
2.    Release of contents of platelet granules cause recruitment  and activation of additional platelets
3.    Thromboxane synthesis induces platelet aggregation
4.    Thrombin generation due to presence of PL

Platelets are pathogenetically more important in arterial thrombi thus antiplatelet agents are very important in arterial thrombosis management.

Venous thrombosis:
1.    Vessel wall is usually normal except if there is direct vessel trauma, extrinsic venous compression or damage due to drugs like chemotherapy
2.    Reduction in venous tone is important in pathophysiology

Venous thrombi can be of two types.

A. Phlebo thrombosis 
This is thrombus formation in an uninflammed vein usually due to stasis or changes in coagulability of blood. This occurs mostly in deep calf veins and varicose veins in the legs originating near valve pockets. They may propagate to extend to popliteal ,femoral and iliac-veins. These are a common source of massive emboli ‘Phlegmasia alba dolens’  (painful white leg) is a condition seen in late pregnancy and puerperium.  In this condition, in addition to iliofemoral thrombosis , there is arterial spasm

B Thrombophlebitis:
In this condition venous wall is inflamed and initiates thrombosis. This is more firmly attached to the vessel wall and also there is much less tendency for propagation Hence there is little chance or embolism.

Cardiac Thrombosis
Intra cardiac thrombus formation can be at 3 sites 

•    Valvular: as in endocarditis
•    Atrial : as in atrial fibrilation ('ball valve thrombus") over MacCallum’s patch is Rheumatic Fever.
•    Ventricular mural thrombus  over site of MI

Fate of Thrombus

- Resolution : if small, the thrombus is rapidly covered by endothelial cells. Then it can Resolved by a combination of retraction, phgocytosis , platelet autolysis, and fibrinolysis 
-  Organisation: there is in growth of vascular granulation tissue. This can result in
 a. recanalisation
 b. collagenisation and-scarring
-    Detachment resulting in thromboembolism
 

Roseola
 - alias exanthem subitum; caused by Herpes virus type 6.
 - children 6 months to 2 years old; spring and fall; incubation 10-15 days.
 - sudden onset of a high fever with absence of physical findings; febrile convulsions are particularly common.
 - fever falls by crisis on the 3rd or 4th day → 48 hours after temperature returns to normal macular or maculopapular rash starting on the trunk and spreading centrifugally.

Hepatitis A virus.
- Hepatitis A (HAV) is a self-limited hepatitis caused by an RNA virus 

- Symptoms last 2 to 4 weeks.
- There is no risk of developing chronic hepatitis in the future.
- Incubation period is short, lasting 2 to 6 weeks.
- Infection is identified by HAV-specific antibodies (IgM if acute, IgG if past disease).
- The usual route of infection is fecal-oral transmission by contaminated food. There is no carrier state and no chronic disease
- Laboratory diagnosis: ELISA test for IgM antibody.
- Vaccine: killed virus.
- Prevention: serum immunoglobulins are available.