Protozoan – single-celled eukaryote organisms.

Reservoirs – alternate or passive host or carrier harbouring pathogenic organisms, without injury to self. Can act as a source for others to infected.

Trophozoite – feeding stage of a protozoan

Cosmopolitan – having worldwide distribution

Gravid – with child; pregnant

Helminthe – worms

Nematodes – roundworms

Trematodes – flukes, flatworms

Cestodes – tapeworms

Hydatid – membranous sac filled with transparent fluid; formed by parasitic worms especially.

Unilocular – having only one internal cavity

Obligate – without another pathway

Pruritic – itchy

Papule – small, circumscribed elevation of the skin

Schizogony – division of cells (especially protozoans), in non-sexual stages of life history of organism

Tachyzoite – rapidly multiplying state in development of tissue phase of certain coccidial infections

Proglottis – one of the free, or nearly free, segments of a tapeworm. Contains male and female repro organs, can live a brief independent existence.

Hydatid sand – embryos of tapeworms in the fluid within a cyst

Oncosphere – first-stage larva of cestodes; emerging from egg and clawing through intermediate hosts intestine

• Protozoa (single cell eukaryotes)
• Helminths (worms)
• Arthropods (jointed appendages, chitinous exoskeleton)

• Amebae
• Flagellates
• Apicomplexa
• Ciliates
• Microsporidia

• Flatworms (flukes and tapeworms)
• Roundworms

• Insects (lice, flies, mosquitoes etc.)
• Arachnids (mites, ticks, spiders, scorpions).

• Definitive hosts harbor the adult or sexual stages of the parasite
• Intermediate hosts harbor the larval or asexual stages of the parasite
• Reservoir hosts maintain the life cycle of a parasite in the absence of humans.

• Symbiosis refers to organisms living together. Often both organisms benefit from this relationship.
• Commensalism is a symbiosis with one organism benefiting without causing harm to the other.
• Mutualism is a symbiosis where both organism benefit; lichens are an example of such an interaction.
  
• Parasitism is a symbiotic relationship where one organism (the parasite) benefits at the expense of the other (the host).

• Fecal examination for ova and parasites (O & P) performed on fresh material or preserved specimens. This examination must include permanent-stained slides and a concentration technique. Wet preparations may be used, but are not essential.
• Antigen detection systems that use ELISA or fluorescent antibody
• Thick and thin blood films usually stained with Giemsa stain
• Molecular techniques, including the polymerase chain reaction have been developed in experimental laboratories for identifying organisms in tissue, body fluids, and feces.

At present about 4000 virus species are known with more than 30,000 strains. How does one actually classify viruses? The International Committee on Taxonomy of Viruses devised a system, based on the genetic material of the virus and the way mRNA is produced (multiplication strategy).

Further subdivisions can be based on items such as (1) genetic material present as one piece or multiple pieces, (2) size of the genome, (3) envelop present or not, (4) morphology.

The decision as to what is species is arbitrary because a species usually contains several strains that may differ substantially (10% or more) in nucleotide sequence. Virus species that exhibit close relationship are grouped into a genus. Genera are grouped into families. Higher taxonomical classifications are rarely used.

The genetic material of viruses can consist of DNA (single or double stranded) or RNA (single or double stranded). The proteins necessary for the construction of complete virions are always made via the information coded in mRNA. By definition, mRNA has positive polarity. There are several different ways in which viral mRNA can be made.

1. Double stranded DNA, from which mRNA is generated.

• Adenoviridae (e.g. adenovirus)

• Poxviridae (e.g. smallpox, vaccinia)

• Herpesviridae (e.g. herpes implex, varicella, Epstein-Barr, CMV)

• Polyomaviridae (e.g. JC virus)

• Papillomaviridae (e.g. warts)

1. Double stranded DNA, from which mRNA is generated. Viral reverse transcriptase produces a negative DNA strand from positive mRNA. The negative DNA strand serves as a template to produce double stranded DNA. Because of this RNA-to-DNA step, they are also known as pararetroviruses.

• Hepadnaviridae (e.g. hepatitis B)

1. Negative single strand DNA, used as a template to produce mRNA.

• Parvoviridae (e.g. parvovirus B19)

1. Double stranded RNA, one strand functions as mRNA.

• Reoviridae (e.g. rotavirus)

1. Negative single strand RNA, used as a template to produce mRNA.

• Rhabdoviridae (e.g. rabies)

• Filoviridae (e.g. Marburg)

• Arenaviridae (e.g. Lassa)

• Bunyaviridae (e.g. Hantavirus)

• Bornaviridae (e.g. bornavirus)

• Orthomyxoviridae (e.g. influenza)

Paramyxoviridae (e.g. mumps and measles)

1. Positive single strand RNA, used to make negative single strand RNA, from which mRNA is produced.

   Flaviviridae (e.g. yellow fever, hepatitis C)

   Picornaviridae (e.g. poliovirus, rhinovirus)

   Togaviridae (e.g. rubella)

   Coronaviridae (e.g. SARS)

   Astro- and Caliciviridae

2. Positive single strand RNA, used as a template to produce negative single strand DNA. This ssDNA is converted to double strand DNA, which then will be used as a template to produce mRNA.

• Retroviridae (e.g. HTLV-1, HIV)

Autoimmune disease is the most frequent cause of overactivity and underactivity of endocrine organs; common in apparently healthy people, especially females.

Iceberg model of endocrine autoimmunity:

Genetic polymorphism

(Environment & other factors)



Autoimmunity

(Autoantibodies & autoreactive T cells)



Autoimmune disease

(Tropic hormone changes)



Organ dysfunction / failure

Autoantibodies:

• Detection of endocrine auto-antibodies is useful to predict autoimmune endocrine failure and to distinguish autoimmune endocrine disease from other types

• May bind to:

  • Cell surface: C’ activation, cytotoxicity

  • Receptors: mimic ligand and stimulate; or block ligand effect; or bind elsewhere and cause down regulation or destruction of receptor

  • Intracellular structures: marker of destructive response e.g. T-cells

  • Secreted protein: inhibit function or effect of protein

Autoreactive lymphocytes: effects on tissues and cells…

• Cytotoxic T-cells and NK cells: killing of tissue cells

• Helper T-cells: release of IL and cytokines, induction of Fas expression and apoptosis

At present, treatment is usually not directed at control of the autoimmunity, rather organ failure is accepted and hormone replacement therapy is given. IDDM and hypothyroidism can now be predicted by genetic polymorphisms, auto-antibodies and hormone measurements; making early intervention and prevention more possible.

Autoimmune thyroid failure:

Grave’s disease: hyperthyroidism caused by stimulating receptor autoantibodies.

Genetics link:

• Incidence in general population (1%): Monozygotic twin concordance (30-60%)

• HLA-DR3 relative risk increased3: incidence in HLA identical siblings (7%)

Autoantibodies to the TSH receptor:

• Long acting thyroid stimulator (LATS)

• Thyroid stimulating immunoglobulin (TSI)

• IgG (in 80-90%): transfer of disease from mother to foetus

Bind receptors -> stimulate activity and growth (hypertrophy and hyperplasia) of the thyroid gland.

Laboratory diagnosis:

• High T3/T4 and low TSH (general primary hyperthyroidism)

• Anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-TG) confirm autoimmunity and predict thyroid failure

• Anti-TSH-R confirms Grave’s disease and predict relapse

Atrophic thyroiditis: chronic autoimmune destructive inflammation that may result in thyroid failure (primary hypothyroidism) associated with anti-TPO and anti-TG.

Thyroid antibodies:

• Occur in apparently healthy people

• Associated with diagnosed hypothyroidism

• (Microsomal) predicts development of thyroid failure

Insulin dependent diabetes mellitus: (IDDM or type 1) autoimmune destruction of islet b-cells causing insulin deficiency.

Genetic link: HLA most significant:

• General population (0.3-0.6%): siblings (6%): monozygotic twins (>20%)

• Markers of risk: e.g. DR3/4, DQB1 show marked increase in relative risk

Autoantibodies against particular antigens predictive of IDDM:

• Islet cell antibodies e.g. ICA, GAD, IA2

• >4 units  40% IDDM within 10 years

• >80 units  100% IDDM within 10 years

• Auto-antigen e.g. Insulin B chain, GAD65

Other related autoimmune conditions include:

• Insulin autoimmune syndrome: (rare – Japanese)

• Autoantibodies bind to insulin --> act as a buffer or reservoir for insulin

• Prolonged insulin action --> delayed hypoglycaemia

• Autoimmune (Type B) insulin resistance: autoantibodies bind insulin receptor  block insulin binding  insulin resistance

Graves’ disease: is an autoimmune disorder produced by autoantibodies to the TSH receptor, thyroglobulin, and thyroid hormones (T₃ & T₄). It is the most common cause of endogenous hyperthyroidism, and is characterized by:

• Hyperthyroidism resulting from hyperfunctional diffuse enlargement of the thyroid

• Infiltrative ophthalmopathy with resultant exophthalmoses, in most, but not all cases

• Localized, infiltrative dermopathy sometimes called peritibial myxoedema in a minority of patients

• Also sometimes finger clubbing (not seen in other thyrotoxicosis)

Pathogenic mechanisms:

Graves’ disease is autoimmune thyroid hyperplasia in which there is an (autoantibodyLong Acting Thyroid Stimulator – LATS) against the cell TSH receptor. This antibody has the same effect as TSH (from pituitary) in stimulating production of thyroid hormones; but in the absence of negative feedback control, results in excess production of thyroid hormones (T3 & T4).

Other immunoglobulins (e.g. TSH growth-stimulating Ig) implicated in the proliferation of thyroid follicular epithelium and stimulation of thyroid epithelial cell activity also contributes to this disease process.

Clinical features of hyperthyroidism: affects many organs…

• Goitre

• Tachycardia

• Weight loss with increased appetite

• Osteoporosis

Many more including: anxiety, menorrhagia, lid retraction/lag, palpitations, atrial fibrillation, diarrhoea, hair loss, warm moist palms, and tremors.

Laboratory findings:

•  In radioactive iodine uptake by the thyroid (hyperfunction)

•  Levels of T₃ and T₄   levels of TSH (primary thyrotoxicosis)

• Presence of LATS immunoglobulin serum (specific to Graves’ disease)

Neoplasms of adrenal cortex: growth disorders are the most important lesions in the adrenal cortex…

Hyperplasia: (diffuse or macro/micro-nodular) - Often-minimal enlargement.

Adenoma:

• Usually small, solitary, poorly encapsulated, yellow nodules

• Larger lesions may contain areas of haemorrhage, cystic change and calcification

• Lipid laden cells, sometimes more pleomorphic, diagnosis difficult

• Many non-functional

Carcinoma:

• Usually large, unencapsulated, highly anaplastic and malignant

• Lymphatic and or haematogenous metastasis to lungs  other organs

• Some are small and difficult to distinguish from adenoma

• Tumours commonly invade vascular channels and metastasis to lung is common

These lesions may result in:

• Hypofunction: acute or chronic adrenal insufficiency; the result of massive destruction of adrenal glands (e.g. Waterhouse-Friderichsen syndrome, meningococcal septicaemia)

• Hyperfunction: e.g. Cushing (excess glucocorticoid), Conn (excess mineralocorticoid) or adrenogenital syndromes (ACTH secretion)

• Normal function

Note: secondary tumours are more common than primary (esp. lung & breast)

Adrenal phaeochromocytoma: uncommon neoplasm arising from medullary neuroendocrine cells (phaeochromocytes); may be

• Sporadic

OR

• Familial: often bilateral  other familial syndromes (e.g. MEN II)

AND

• Secretory: (catecholamine production) associated with paroxysmal or persistent hypertension headache, sweating, tachycardia, fatigue, tremor, GIT and cardiac complications; may lead to other endocrine disturbances (e.g. Cushing syndrome)

OR

• Non-secretory

Most are benign (90%) though histological distinction is difficult – only certain criterion is metastasis; diagnosed by radiographic imaging and plasma catecholamine assay.

Note: paraganglioma is identical neoplasm arising in extra-adrenal neuroendocrine cells (paraganglionic tissue) related to ANS in head and neck.

Tumours of extra-adrenal paraganglia include:

• Neuroblastoma (malignant)

• Ganglioneuroma (benign)

Aetiology:

Hyperfunction of the parathyroid may result from

1. Primary hyperparathyroidism: usually due to a parathyroid adenoma (up to 90%), or hyperplasia (10%) including MEN I & II syndromes and rarely carcinoma (<5%)>

2. Secondary hyperparathyroidism: hyperplasia usually in response to hypocalcaemia as in chronic renal failure; less commonly e.g. Vitamin D deficiency, intestinal malabsorption, calcitonin producing tumour, pseudo-hypoparathyroidism

3. Tertiary hyperparathyroidism: where a functioning autonomous adenoma arises in the hyperplastic glands of secondary hyperparathyroidism; includes ectopic secretions PTH-like-substance by non-parathyroid tumours (e.g. lung, renal and ovarian cancer)

Parathyroid adenoma:

• Typically solitary (suspect nodular hyperplasia if >1)

• Most in inferior glands (may be ectopic and difficult to locate)

• Usually chief cell type, monoclonal origin; rarely associated with MEN I

• Most are sporadic; of these 25% have similar mutation to familial forms on chromosome 11.

Parathyroid hyperplasia:

• Typically involves all glands (may be asymmetrical)

• Mainly chief cells, may have a nodular pattern, polyclonal origin

• May be familial (homozygous loss of suppressor gene on chromosome 11, MEN I or less commonly MEN IIa)

Parathyroid carcinoma:

• Very rare, variable size

• Diagnosis difficult (require invasion  metastasis)

• Normally slowly progressive

Consequences and complications:

Hyperparathyroidism   PTH   serum Ca²⁺ levels (hypercalcemia)  metastatic calcification in kidneys, blood vessels, lungs, gastro-intestinal tract, skin conjunctiva etc.

Characterized by ‘painful bones, renal stones, abdominal groans’ and psychic moans’ with:

• Resorption of bone leading to osteoporosis or osteitis fibrosa cystica, collections of osteoclasts with haemorrhage (‘brown tumours’) and possibly pathological fractures.

• Renal stone formation is a feature of hypercalcemia and may interfere with renal function (nephrocalcinosis).

• Gastrointestinal disturbances including constipation, peptic ulcers, pancreatitis and gall stones.

• Central nervous system alterations (emotional disorders) including depression and lethargy.

(May also exhibit muscle atrophy)

Pituitary adenoma: (anterior lobe) most important lesion / tumour of the pituitary…

• It is benign, rarely infiltrate locally and may be non-functional (majority) or functional.

• Found in up to 20% of population post-mortem and represents about 15% of all intracranial neoplasms.

Other neoplastic causes of pituitary enlargement:

• Atypical adenoma and carcinoma: (anterior pituitary) rare, usually non-functional

• Craniopharyngioma: above the sella turcica (Rathke’s pouch origin)

• Posterior pituitary neoplasm: commonest is glioma

• Secondary neoplasm: more common in posterior pituitary, may present as diabetes insipidus (breast and lung commonest primary sites)

Non-neoplastic causes of pituitary enlargement:

• Congenital adrenal hyperplasia

• Primary hypothyroidism

• Pituitary gland enlargement secondary to dural arteriovenous fistula in the cavernous sinus

• Pregnancy results in physiologic pituitary enlargement.

Mechanical effects: the pituitary gland is situated within the sella turcica of the sphenoid bone, at the base of the skull; enlargement may cause

• Raised intracranial pressure: headache, rarely herniation

• Bony erosion

• Local pressure (atrophic or compressive) effects on:

  • Third ventricle

  • Hypothalamus

  • Optic chiasma: visual field defects e.g. bitemporal hemianopia, atrophy

  • Cranial nerves III, IV, V, VI: nerve palsies

Hormonal secretion:

• Effects vary depending on type of hormone/s affected (secretion and amount)
  

Note: functioning tumour of one type of pituitary cell (hyperfunction) may cause atrophy (hypofunction) of other types through expansive growth and pressure effects; though 75% specific tissue or cell loss is required to affect function.

Clinical syndromes and pituitary malfunction: