HAEMORRHAGIC DISORDERS

Normal homeostasis depends on

 -Capillary integrity and tissue support.

- Platelets; number and function

(a) For integrity of capillary endothelium and platelet plug by adhesion and aggregation

(b) Vasoactive substances for vasoconstriction

(c) Platelet factor for coagulation.

(d) clot retraction.

- Fibrinolytic system(mainly Plasmin) : which keeps the coagulatian system in check.

Coagulation disorders

These may be factors :

Deficiency .of factors

• Genetic.
• Vitamin K deficiency.
• Liver disease.
• Secondary to disseminated intravascular coagulation.or defibrinatian

Overactive fibrinolytic system.

Inhibitors of  the factars (immune, acquired).

Anticoagulant therapy as in myocardial infarctian.

Haemophilia. Genetic disease transmitted as X linked recessive trait. Comman in Europe. Defect in fcatorVII  Haemophilia A .or in fact .or IX-Haemaphilia B (rarer).

Features:

• May manifest in infancy or later.
• Severity depends  on degree of deficiency.
• Persistant woundbleeding.
• Easy Bruising with Haemotoma formation

Nose bleed , arthrosis, abdominal pain with fever and leucocytosis

Prognosis is good with prevention of trauma and-transfusion of Fresh blood or fTesh plasma except for danger of developing immune inhibitors.

Von Willebrand's disease. Capillary fragility and decreased factor VIII (due to deficient stimulatory factor). It is transmitted in an autosomal dominant manner both. Sexes affected equally

Vitamin K  Deficiency. Vitamin K is needed for synthesis of factor II,VII,IX and X.

Deficiency maybe due to:

Obstructive jaundice.

Steatorrhoea.

Gut sterilisation by antibiotics.

Liver disease results in :

Deficient synthesis of factor I II, V, Vll, IX and X  Incseased fibrinolysis (as liver is the site of detoxification of activators ).

Defibrination syndrome. occurs when factors are depleted due to disseminated .intravascular coagulation (DIC). It is initiated by endothelial damage or tissue factor entering the circulation.

Causes

Obstetric accidents, especially amniotic fluid embolism. Septicaemia. .

Hypersensitivity reactions.

Disseminated malignancy.

Snake bite.

Vascular defects :

(Non thrombocytopenic purpura).

Acquired :

Simple purpura a seen in women. It is probably endocrinal

Senile parpura in old people due to reduced tissue support to vessels

Allergic or toxic damage to endothelium due to  Infections like Typhoid Septicemia

Col!agen diseases.

Scurvy

Uraemia damage to  endothelium (platelet defects).

Drugs like aspirin. tranquillisers, Streptomvcin pencillin etc.

Henoc schonlien purpura Widespeard vasculitis due to hypersensitivity to bacteria or foodstuff

It manifests as :

Pulrpurric rashes.

Arthralgia.

Abdominal pain.

Nephritis and haematuria.

Hereditary :

(a) Haemhoragic telangieclasia. Spider like tortous vessels which bleed easily. There are disseminated lesions in skin, mucosa and viscera.

(b) Hereditary capillary fragilily similar to the vascular component of von Willbrand’s disease

.(c) Ehler Danlos Syndrome which is a connective tissue defect with skin, vascular and joint manifestations.

Platelet defects

These may be :

(I) Qualitative thromboasthenia and thrombocytopathy.

(2) Thrombocytopenia :Reduction in number.

(a) Primary or idiopathic thrombocytopenic purpura.

(b) Secondary to :

(i) Drugs especially sedormid

(ii) Leukaemias

(iii) Aplastic-anaemia.

Idiopathic thrombocytopenic purpura (ITP). Commoner in young females.

Manifests as :

Acute self limiting type.

Chronic recurring type.

Features:

(i) Spontaneous bleeding and easy bruisability

(ii)Skin (petechiae), mucus membrane (epistaxis) lesions and sometimes visceral lesions involving any organ.

Thrombocytopenia with abnormal forms of platelets.

Marrow shows increased megakaryocytes with immature forms,

vacuolation, and lack of platelet budding.

Pathogenesis:

hypersensitivity to infective agent in acute type.

Plasma thrombocytopenic factor ( Antibody in nature) in chronic type

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.

Fanconi’s syndrome

Characterized by the failure of the proximal renal tubules to resorb amino acids, glucose, and phosphates.
May be inherited or acquired.

Clinical manifestations include 

glycosuria, hyperphosphaturia, hypophosphatemia, aminoaciduria, and systemic acidosis.

Acne vulgaris is a chronic inflammatory disorder usually present in the late teenage years characterized by comedones, papules, nodules, and cysts.
 - subdivided into obstructive type with closed comedones (whiteheads) and open comedones (blackheads) and the inflammatory type consisting of papules, pustules, nodules, cysts and scars.
 - pathogenesis of inflammatory acne relates to blockage of the hair follicle with keratin and sebaceous secretions, which are acted upon by Propionibacterium acnes (anaerobe) that causes the release of irritating fatty acids resulting in an inflammatory response.
 - pathogenesis of the obstructive type (comedones) is related to plugging of the outlet of a hair follicle by keratin debris.
 - chocolate, shellfish, nuts iodized salt do not aggravate acne.
 - obstructive type is best treated with benzoyl peroxide and triretnoin (vitamin A acid)
 - treatment of inflammatory type is the above plus antibiotics (topical and/or systemic; erythromycin, tetracycline, clindamycin).

OEDEMA

 Excessive accumulation of fluid in the extra vascular compartment (intersttitial tissues). This includes ascites (peritoneal sac), hydrothorax (pleural cavity) hydropericardium (pericardial space) and anasarca (generalised)

Factors which tend to accumulate interstitial fluid are:

- Intravascular hydrostatic pressure

- Interstitial osmotic pressure.

- Defective lymphatic drainage.

- Increased capillary permeability.

Factors that draw fluid into circulation are:

- Tissue hydrostatic-pressure (tissue tension).

- Plasma osmotic pressure,

Oedema fluid can be of 2 types:

A. Exudate.

It is formed due to increased capillary permeability as in inflammation.

B. Transudate

Caused by alterations of hydrostatic and osmotic pressures.

Local Oedema

1. Inflammatory oedema. Mechanisms are.

- Increased capillary permeability.

- Increased vascular hydrostatic pressure.

- Increased tissue osmotic pressure.

2.Hypersensitivity reactions especially types I and III

3. Venous obstruction :

- Thrombosis.

- Pressure from outside as in pregnancy, tourniquets.

4. Lymphatic obstruction:

- Elephantiasis in fillariasis

- Malignancies (Peau de orange in breast cancer).

Generalized Oedema

1.         Cardiac oedema

Factors :Venous pressure increased.

2. Renal oedema

- Acute glomerulonephritis

- Nephrotic syndrome

3. Nutritional (hypoproteinaemic) oedema. it is seen in

- Starvation and Kwashiorkor

- Protein losing enteropathy

4.  Hepatic oedema (predominantly ascites)

Factors:

- Fall in plasma protein synthesis

- Raised regional lymphatic and portal venous pressure

5. Oedema due to adrenal corticoids

As in Cushing's Syndrome

Pulmonary oedema

- Left heart failure and mitral stenosis.

- Rapid flv infusion specially in a patient of heart failure.

Herpes simplex is subdivided into type 1 and 2, the former usually developing lesions around the lips and mouth and the latter producing vesicular lesions in the genital region 
 - contracted by physical contact; incubation 2-10 days.
 - primary HSV I usually is accompanied by systemic signs of fever and Lymphadenopathy, while recurrent herpes is not associate with systemic signs.
 - dentists often become infected by contact with patient saliva and often develop extremely painful infections on the fingers (herpetic whitlow).
 - Herpes viruses remain dormant in sensory ganglia and are reactivated by stress, sunlight, menses, etc. 

 - Herpes gingivostomatitis is MC primary HSV 1 infectionÆpainful, vesicular eruptions that may extend for the tongue to the retropharynx.
 - Herpes keratoconjunctivitis (HSV 1)
 - Kaposi's varicelliform eruption refers to an HSV 1 infection superimposed on a previous dermatitis, usually in an immunodeficient person.
 - laboratory: culture; ELISA test on vesicle fluid; intranuclear inclusions within multinucleated squamous cells in scrapings (Tzanck preps) of vesicular lesions.