Systemic Candidiasis (Candidosis; Moniliasis)

Invasive infections caused by Candida sp, most often C. albicans, manifested by fungemia, endocarditis, meningitis, and/or focal lesions in liver, spleen, kidneys, bone, skin, and subcutaneous or other tissues.

Infections due to Candida sp account for about 80% of all major systemic fungal infections.

Symptoms and Signs

Esophagitis is most often manifested by dysphagia. Symptoms of respiratory tract infections are nonspecific, such as cough. Vaginal infections cause itching, burning, and discharge. Candidemia usually causes fever, but other symptoms are typically nonspecific. Sometimes, a syndrome develops resembling bacterial sepsis, with a fulminating course that may include shock, oliguria, renal shutdown, and disseminated intravascular coagulation.

Hematogenous endophthalmitis starts as white retinal plaques that can cause blindness as destructive inflammation progresses, extending to opacify the vitreous and causing potentially irreversible scarring. Most often, there are no symptoms in early stages of Candida endophthalmitis. If treatment is not begun before symptoms appear, significant or even total loss of vision is likely to occur in the affected eye. In neutropenic patients, eye involvement is more often manifested by retinal hemorrhages; papulonodular, erythematous, and vasculitic skin lesions may also develop.

Bronchiectasis 
- Bronchiectasis is abnormal and irreversible dilatation of the bronchi and bronchioles (greater than 2 mm in diameter) secondary to inflammatory weakening of bronchial wall.
- Occur in childhood and early adult life
- Persistent cough with copious amount of foul smelling purulent sputum

Aetiopathogenesis
Bronchial wall destruction is due to:
- Endobronchial obstruction due to foreign body
- Infection due to local obstruction or impaired defence mechanism 

Clinical conditions:
- Hereditary and congenital factors
- Obstruction
- Secondary complication

Hereditary and congenital factors:
- Congenital bronchiectasis due to developmental defects
- Cystic fibrosis causing defective secretion resulting in obstruction
- Hereditary immune defiency diseases
- Immotile cilia syndrome- immotile cilia of respiratory tract, sperms causing Kartagener’s syndrome (bronchiectasis, situs inversus and sinusitis) and male infertility
- Allergic bronchial asthma patients

Obstruction:

Localised variety in one part of bronchial system.
Obstruction can be due to
Foreign body
Endobronchial tumors
Hilar lymph nodes
Inflammatory scarring (TB)

Secondary complication:

Necrotizing pneumonia in Staph infection and TB

Morphologic changes

- Affects distal bronchi and bronchioles
- Lower lobes more frequently
- Lungs involved diffusely/segmentally
- Left lower lobe than right
- Pleura fibrotic & thickened adherent to chest wall

C/S lung: Honey-combed appearance

Microscopic examination:
Bronchiole-dilated
Bronchial epithelium-normal, ulcerated, squamous metaplasia
Bronchial wall-infiltration by ac & Ch inflammatory cells,
destruction of muscle, elastic tissue 
Lung parenchyma-fibrosis, surrounding tissue pneumonia
Pleura-fibrotic and adherent

Osteogenesis Imperfecta (OI) (Brittle bone diseases) 

It is a group of hereditary disorders caused by gene mutations that eventuate in defective synthesis of and thus premature degradation of type I collagen. The fundamental abnormality in all forms of OI is too little bone, resulting in extreme susceptibility to fractures. The bones show marked cortical thinning and attenuation of trabeculae. 

Extraskeletal manifestations also occur because type I collagen is a major component of extracellular matrix in other parts of the body. The classic finding of blue sclerae  is attributable to decreased scleral collagen content; this causes a relative transparency that allows the underlying choroid to be seen. Hearing loss can be related to conduction defects in the middle and inner ear bones, and small misshapen teeth are a result of dentin deficiency 

HYPERTENSIVE VASCULAR DISEASE 

Malignant hypertension 
A small percentage of HTN patients (5%) present with a rapidly rising blood pressure that, if untreated, leads to death within 1 to 2 years. 

systolic pressures -> 200 mm Hg or diastolic pressures -> 120 mm Hg 
Associated with renal failure and retinal hemorrhages
Most commonly is superimposed on preexisting benign hypertension

Hypertension (HTN) has the following complications

- stroke (CVD) 
- multi-infarct dementia
- atherosclerotic coronary heart disease 
- cardiac hypertrophy and heart failure (hypertensive heart disease) 
- aortic dissection 
- renal failure

Essential HTN Accounts for 90% to 95% of all cases

SecondaryHTN 

Renal - > Acute glomerulonephritis Chronic renal disease 
Endocrine - >  Cushing syndrome, Hypothyroidism (myxedema) Hyperthyroidism (thyrotoxicosis) Pregnancy-induced (pre-eclampsia)
Cardiovascular  - > Coarctation of aorta 

Neurologic

Psychogenic,  Increased intracranial pressure 

PATHOGENESIS
most cases (95%) are idiopathic (essential hypertension)
Most of the remaining cases (secondary hypertension) are due to primary renal disease, renal artery narrowing 
Gene defects in enzymes involved in aldosterone metabolism 
 Mutations in proteins that affect sodium resorption as in Liddle syndrome
 
 Genetic factors - > familial clustering of hypertension 
 
 Environmental factors such as stress, obesity, smoking, physical inactivity, and high levels of salt consumption, modify the impact of genetic determinants

Morphology
HTN is associated with arteriolosclerosis (small arterial disease) 

Two forms of small blood vessel disease are hypertension-related: 
1- hyaline arteriolosclerosis 
2- hyperplastic arteriolosclerosis 

Hyaline arteriolosclerosis
Associated with benign hypertension. 
-marked by homogeneous, pink hyaline thickening of the arteriolar walls, and luminal narrowing. 

Hyperplastic arteriolosclerosis
It is more typical of severe hypertension. 
- "onionskin," concentric, laminated thickening of arteriolar walls and luminal narrowing. 
- The laminations consist of smooth muscle cells and thickened, reduplicated basement membrane. 

DISORDERS OF BLOOD VESSEL HYPERREACTIVITY
Several disorders are characterized by inappropriate or exaggerated vasoconstriction of blood vessels: 
1- Raynaud Phenomenon 
2- Myocardial Vessel Vasospasm 

Raynaud Phenomenon
- results from exaggerated vasoconstriction of arteries and arterioles in the extremities (the fingers and toes, but also sometimes the nose, earlobes, or lips). 
-restricted blood flow induces paroxysmal pallor or cyanosis
- involved digits characteristically show "red-white-andblue" color changes from most proximal to most distal 

Myocardial Vessel Vasospasm 

Causes: 1- vasoactive mediators - > prolonged vascular contraction; 
- endogenous (e.g., epinephrine released by pheochromocytomas) or exogenous (cocaine or phenylephrine). 
2- Elevated thyroid hormone -> increase sensitivity of vessels to catecholamines 
3- autoantibodies and T cells in scleroderma vascular instability and vasospasm. 
4- extreme psychological stress (release of catecholamines)

Cardiac raynaud

When vasospasm of cardiac arterial or arteriolar bed is of sufficient duration (20 to 30 min ) myocardial infarction occurs

acute microscopic area of necrosis characterized by mycotic hypercontraction (contraction band necrosis)

subacute and chronic cases - > microscopic foci of granulation tissue or scar

ATROPHY
It is the acquired decrease in the size of an organ due to decrease in the size and/or number of its constituent cells.
Causes:
(1) Physiological

- Foetal involution.
    o    Branchial clefts.
    o    Ductus arterious.
- Involution of thymus and other lymphoid organs in childhood and adolescence.
- In adults:
    o    Post-partum uterus.
    o    Post-menopausal ovaries and uterus
    o    Post-lactational breast
    o    Thymus.
(2) Pathological:
- Generalised as in

    o    Ageing.
    o    Severe starvation and cachexia
- Localised :
    o    Disuse atropy of bone and muscle.
    o    Ischaemic atrophy as in arteriosclerotic kidney. .
    o    Pressure atrophy due  to tumours and of kidney in hydronephrosis.
    o    Lack of trophic stimulus to endocrines and gonads.
 

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