Portal hypertension

 It is elevation of the portal venous pressure (normal 7 m.m Hg). 

 Causes:-
 1- Presinusoidal    
 2- Sinusoidal        
 3- Postsinusoidal
 
Presinusoidal:- 
  a. Massive splenomegaly and increased splenic blood flow.
  b. Portal vein obstruction by thrombosis or outside pressure.
  c. Portal venular obstruction at the portal tracts e.g. by fibrosis, granuloma or chronic hepatitis. 

Sinusoidal:-  
Cirrhosis due to perisinusoidal fibrosis

Postsinusoidal:-  
a.Alcoholic hepatitis leading to perivenular fibrosis.
b. Cirrhosis leading to interference with the blood flow and  to arterio -venous anastomosis resulting in increased venous blood pressure.
c. Veno -occlusive diseases of the liver caused by some drugs & plant toxins. It results in progressive fibrous occlusion of the hepatic venules and vein radicals.
d. Budd- Chiari syndrome: It is hepatic vein thrombosis. 30% of cases have no apparent cause. It produces portal hypertension and hepatomegaly. It is fatal if not treated. 
e. obstruction of major hepatic vein by tumors. 
f. Right sided heart failure and constrictive pericarditis 

Effects of portal hypertension: 

Ascitis
 
It is intraperitoneal accumulation of serous fluid which is a Transudate . It causes abdominal distension.  

Causes

a. Increased hydrostatic pressure` in the portal venous system. 
b. Decreased albumin synthesis in the liver…..decreased colloid osmotic pressure of plasma.
c. Sodium and water retension due to secondary hyperaldosteronism and ADH secretion. 
d. Leakage of hepatic lymph through the hepatic capsule due to hepatic vein obstruction.  

Splenomegaly:-   It results from chronic venous congestion.
- The spleen enlarged with capsular adhesions.
- It shows Gamma Gandi nodules.  - There may be hyperspelenism.  

Porto-Systemic venous anastomosis:-  Present in the following sites Esophageal variesis. Rupture of these vessels is the main cause of death.
Around the umbilicus  “Caput meduci”. Ano-rectal vessels. 
 

Herpes zoster, or shingles
 - represents reactivation of a latent varicella-zoster infection.
 - virus lies dormant in sensory dorsal root ganglia and when activated involves the distribution (dermatome) of the sensory nerve with a painful vesicular eruption.
 - trigeminal verve distribution → Ramsay Hunt syndrome
 - may indicate the presence of advanced neoplastic disease or be a complication of chemotherapy.

FUNGAL INFECTION

Histoplasmosis

A disease caused by Histoplasma capsulatum, causing primary pulmonary lesions and hematogenous dissemination.

Symptoms and Signs

The disease has three main forms. Acute primary histoplasmosis is usually asymptomatic

Progressive disseminated histoplasmosis follows hematogenous spread from the lungs that is not controlled by normal cell-mediated host defense mechanisms. Characteristically, generalized involvement of the reticuloendothelial system, with hepatosplenomegaly, lymphadenopathy, bone marrow involvement, and sometimes oral or GI ulcerations occurs, particularly in chronic cases

Progressive disseminated histoplasmosis is one of the defining opportunistic infections for AIDS.

Chronic cavitary histoplasmosis is characterized by pulmonary lesions that are often apical and resemble cavitary TB. The manifestations are worsening cough and dyspnea, progressing eventually to disabling respiratory dysfunction. Dissemination does not occur

Diagnosis

Culture of H. capsulatum from sputum, lymph nodes, bone marrow, liver biopsy, blood, urine, or oral ulcerations confirms the diagnosis

Anemia (Disorder of Hematopoietic System) - Probably the most common effect of nutritional deficiency. Any factor that decreases hematopoiesis can cause an anemia.

A. Iron deficiency - Widely recognized as the most important cause of anemia, It is indicated that ½ of all pregnant women and infants are affected, as are ~13% of all adult women.

1. Dietary factors - Availability of iron from different food sources and mixtures.
2. Malabsorption – One third of patients with inflammatory bowel disease (IBD) have recurrent anemia and 30% or more of patients who have had partial gastrectomy will develop iron deficiency anemia.
3. Blood loss - Menses, gastrointestinal bleeding 
4. Increased demand - Pregnancy, growth in children.
5. Congenital - Atransferrinemia
6. Importance of multiple factors.
7. Pathophysiology - Initially iron is mobilized from reticuloendothelial stores and increased intestinal absorption occurs. Total iron stores are depleted, serum iron levels fall. In severe cases in peripheral blood, the red cells become smaller (microcytic) and their hemoglobin content is reduced (hypochromic).  

B. Megaloblastic anemias- Characterized by the presence of abnormal WBCs and RBCs. In severe cases, megaloblasts (abnormal red cell precursors) may be present. These anemias are a consequence of disordered DNA synthesis.
1. Folate deficiency - Can be caused by:
a. Dietary deficiency
b. Malabsorption (celiac disease)
c. Increased demand (pregnancy & lactation)
d. Drugs - methotrexate, anticonvulsants, oral contraceptives, alcoholism.
e. Liver disease

2. Cobalamin (vitamin B12) deficiency - Almost always a secondary disorder that can  be caused by:

a. Intrinsic factor deficiency (pernicious anemia due to autoimmune destruction of the gastric mucosa)

b. Malabsorption

3. Pyridoxine (vitamin B6) deficiency- most commonly associated with alcoholism.

C. Other factors known to be frequently associated with anemia would include protein-calorie malnutrition, vitamin C deficiency, and pyridoxine deficiency (usually associated with alcoholism).

D. Other anemias not particularly associated with nutritional disease would include hemolytic anemia
(decreased red cell life span) and aplastic anemia (failure of marrow to produce new cells).  

Parkinson’s disease
a. Characterized by the degeneration of neurons in the basal ganglia, specifically the substantia nigra and striatum.
b. Histologic findings in affected neurons include Lewy bodies.
c. Clinically, the disease affects involuntary and voluntary movements. Tremors are common. Symptoms include pin-rolling tremors, slowness of movements, muscular rigidity, and shuffling gait.

SPIROCHETAL DISEASE

Syphilis

A contagious systemic disease caused by the spirochete Treponema pallidum, characterized by sequential clinical stages and by years of latency.

ACQUIRED SYPHILIS

T. pallidum is a delicate spiral organism about 0.25 µm wide and from 5 to 20 µm long, identified by characteristic morphology and motility with a darkfield microscope or fluorescent techniques

In acquired syphilis, T. pallidum enters through the mucous membranes or skin, reaches the regional lymph nodes within hours, and rapidly disseminates throughout the body. In all stages of disease, perivascular infiltration of lymphocytes, plasma cells, and, later, fibroblasts causes swelling and proliferation of the endothelium of the smaller blood vessels, leading to endarteritis obliterans.

In late syphilis, T. pallidum elicits a granulomatous-like (gummatous) reaction causing masses, ulcerations, and necrosis. Inflammation may subside despite progressive damage, especially in the cardiovascular and central nervous systems.

The CNS is invaded early in the infection. During the secondary stage of the disease, > 30% of patients have abnormal CSF and may have symptoms of meningitis

Symptoms, Signs, and Course

The incubation period of primary syphilis can vary from 1 to 13 wk but is usually from 3 to 4 wk. The disease may present at any stage and long after the initial infection

Primary stage: The primary lesion, or chancre generally evolves and heals within 4 to 8 wk in untreated patients. After inoculation, a red papule quickly erodes to form a painless ulcer with an indurated base that, when abraded, exudes a clear serum containing numerous spirochetes

The regional lymph nodes usually enlarge painlessly and are firm, discrete, and nontender. Chancres occur on the penis, anus, and rectum in men and on the vulva, cervix, and perineum in women. Chancres may also occur on the lips or the oropharyngeal or anogenital mucous membranes.

Secondary stage: Cutaneous rashes usually appear within 6 to 12 wk after infection and are most florid after 3 to 4 mo.

Frequently, generalized, nontender, firm, discrete lymphadenopathy and hepatosplenomegaly are palpable. Over 80% of patients have mucocutaneous lesions, 50% have generalized lymphadenopathy, and about 10% have lesions of the eyes (uveitis), bones (periostitis), joints, meninges, kidneys (glomerulitis), liver, and spleen.

Acute syphilitic meningitis may develop, with headache, neck stiffness, cranial nerve lesions, deafness, and, occasionally, papilledema.

Condyloma lata--hypertrophic, flattened, dull pink or gray papules at the mucocutaneous junctions and in moist areas of the skin--are extremely infectious. Hair often falls out in patches, leaving a moth-eaten appearance (alopecia areata).

Latent stage

In the early latent period (< 2 yr after infection), infectious mucocutaneous relapses may occur, but after 2 yr contagious lesions rarely develop, and the patient appears normal. About 1/3 of untreated persons develop late syphilis

Late or tertiary stage: Lesions may be clinically described as (1) benign tertiary syphilis of the skin, bone, and viscera, (2) cardiovascular syphilis, or (3) neurosyphilis.

The typical lesion is a gumma, an inflammatory mass that evolves to necrosis and fibrosis and that is frequently localized but may diffusely infiltrate an organ or tissue

Benign tertiary syphilis of the bones results in either periostitis with bone formation or osteitis with destructive lesions causing a deep, boring pain, characteristically worse at night. A lump or swelling may be palpable.

Cardiovascular syphilis: A dilated, usually fusiform aneurysm of the ascending or transverse aorta, narrowing of the coronary ostia, or aortic valvular insufficiency usually appears 10 to 25 yr after the initial infection

Neurosyphilis

In meningovascular neurosyphilis, brain involvement is signaled by headache, dizziness, poor concentration, lassitude, insomnia, neck stiffness, and blurred vision. Mental confusion, epileptiform attacks, papilledema, aphasia, and mono- or hemiplegia may also occur

Diagnosis:

Two classes of serologic tests for syphilis (STS) aid in diagnosing syphilis and other related treponemal diseases: screening, nontreponemal tests using lipoid antigens detect syphilitic reagin and include the Venereal Disease Research Laboratory (VDRL) and the rapid plasma reagin (RPR) tests. Specific treponemal tests detect antitreponemal antibodies and include fluorescent treponemal antibody absorption (FTA-ABS) test, microhemagglutination assay for antibodies to T. pallidum (MHA-TP), and Treponema pallidum hemagglutination assay (TPHA).

In darkfield microscopy, light is directed obliquely through the slide so that rays striking the spirochetes cause them to appear as bright, motile, narrow coils against a dark background