Hepatic failure 
Etiology. Chronic hepatic disease (e.g., chronic active hepatitis or alcoholic cirrhosis) is the most common cause of hepatic failure although acute liver disease may also be responsible.

- Widespread liver necrosis may be seen with carbon tetrachloride and acetaminophen toxicity. Widespread steatosis is seen in Reye's syndrome, a cause of acute liver failure most often seen in children with a recent history of aspirin ingestion for an unrelated viral illness. 
- Massive necrosis may also be seen in acute viral hepatitis, after certain anesthetic agents, and in shock from any cause. 

Clinical features. Hepatic failure causes jaundice, musty odor of breath and urine, encephalopathy, renal failure (either by simultaneous toxicity to the liver and kidneys or the hepatorerial syndrome), palmar erythema, spider angiomas, gynecomastia , testicular atrophy 

Keratoses (Horny Growth)
1. Seborrheic keratosis is a common benign epidermal tumor composed of basaloid (basal cell-like) cells with increased pigmentation that produce a raised, pigmented, "stuck-on" appearance on the skin of middle-aged individuals.
 - they can easily be scraped from the skin's surface.
 - frequently enlarge of multiply following hormonal therapy.
 - sudden appearance of large numbers of Seborrheic keratosis is a possible indication of a malignancy of the gastrointestinal tract (Leser-Trelat sign).

 2. An actinic keratosis is a pre-malignant skin lesion induced by ultraviolet light damage.
 - sun exposed areas.
 - parakeratosis and atypia (dysplasia) of the keratinocytes.
 - solar damage to underlying elastic and collagen tissue (solar elastosis).
 - may progress to squamous carcinoma in situ (Bowen's disease) or invasive cancer.

 3. A keratoacanthoma is characterized by the rapid growth of a crateriform lesion in 3 to 6
weeks usually on the face or upper extremity.
 - it eventually regresses and involutes with scarring.
 - commonly confused with a well-differentiated squamous cell carcinoma. 

Glycogen storage diseases (glycogenoses)

1. Genetic transmission: autosomal recessive.

2. This group of diseases is characterized by a deficiency of a particular enzyme involved in either glycogen production or degradative pathways.

Diseases include:
on Gierke disease (type I)
(a) Deficient enzyme: glucose-6-phosphatase.
(b) Major organ affected by the buildup of glycogen: liver.

Pompe disease (type II)

(1) Deficient enzyme: α-glucosidase(acid maltase).
(2) Major organ affected by the buildup of glycogen: heart.

Cori disease (type III)
(1) Deficient enzyme: debranching enzyme (amylo-1,6-glucosidase).
(2) Organs affected by the buildup of glycogen: varies between the heart, liver, or skeletal muscle.

Brancher glycogenosis (type IV)
(1) Deficient enzyme: branching enzyme.
(2) Organs affected by the buildup of glycogen: liver, heart, skeletal muscle, and brain.

McArdle syndrome (type V)
(1) Deficient enzyme: muscle phosphorylase.
(2) Major organ affected by the buildup of glycogen: skeletal muscle.

Autoimmune(acquired) Haemolytic anaemia

Auto antibodies are usually Ig g type (may be Ig M or Ig A). They may or may not bind complement and may be active in warm or cold temperature  They may be complete (agggIutinating) or incomplete. Haemolysis s may be intravascular  due to destruction of the antibody coated cells by RE system.

Causes:

a. Idiopathic
b. Secondary to
o    Drugs - Methyldopa, Mefanamic acid

o    Disease like
    -> Infections especially viral.
    -> Autoimmune disease especially SLE.
    -> Lymphomas and chronic  lymphatic leukaemia.
    -> Tumours.
    
Diagnosis : is based on

•    Evidences of haemolytic  anaemia.
•    Demonstration of antibodies

    - On red cell surface by direct Coomb’s test
    - In serum by indirect Coomb’s test.

POLYCYTHEMIA

 It is an increase in number of RC per unit volume of blood (Hb more than 1.9.5 gms% and 18 gms% for women)
 
Causes :

True polycythemia.
- Idiopathic Polythemia vera.

- Secondary to :

    o    Hypoxia of high altitude , heart disease, chronic lung disease etc.
    o    Erythopoietin  oversecretion as in renal diseases , tumours of liver, kidney and adrenal etc.
    o    Compensatory in haemogIobinopathies
    
- Relative polycythemia due to reduction in plasma volume as in dehydration or in redistribution off fluids

Polycythemia vera: It is a myeloprolifeative disorder, usually terminating in myelosclerosis.

Features: are due to hypervolaemic circulation and tendency to tbrombosis and haemorrhage 

    -Headaches, dizziness and cardiovascular accidents.
    -Hypertension.
    -Peripheral vascular thrombosis.
    -GIT bleeding. retinal haemorrhage.
    -Gout.
    -Pruritus.

Blood Finding

-Increased Hb. PCV and RBC count.
-Leucocytosis with high alkaline  phosphatase.
-Platelets increased.

Marrow picture Hypercellular with  increase in precursors of all series 
Course Chronic course ending in myelosclerosis or acute  leukaemia.
 

N. meningiditis

Major cause of fulminant bacteremia and meningitis.  Has a unique polysaccharide capsule.  It is spread person to person by the respiratory route.  Frequently carried in nasopharynx, and carriage rates increased by close quarters.  Special risk in closed populations (college dorms) and in people lacking complement.  Sub-saharan Africa has a “meningitis belt.”

Pathogenesis is caused by adherence factors that attach to non-ciliated nasopharyngeal epithelium. These factors include pili which promote the intial epithelial (and erythrocyte) attachment, and Opa/Opc surface binding proteins.

Adherence stimulates engulfment of bacteria by epithelial cells.  Transported to basolateral surface.

The polysaccharide capsule is a major virulence factor that prevents phagocytosis and lysis. 

A lipo-oligosaccharide endotoxin also contributes to sepsis.