Health Information

Neurotransmitters
Acetylcholine
Norepinephrine
Epinephrine
Dopamine
Serotonin
Histamine

Glutamate
Aspartate
Glycine
GABA

Substance P
Vasopressin
Oxytocin etc..

NO
CO
Adenosine

ACETYLCHOLINE
Location;
- Parasympathetic post ganglionic & all the pre- ganglionic neurons of the autonomic nervous system
- Many nuclei & nerve tracts of the CNS - Neuromuscular junction of skeletal muscle
Acetylcholine has a simple structure,
It is the acetyl ester of choline

SYNTHESIS OF ACETYLCHOLINE
Release of Acetylcholine & binding to receptors,
Acetylcholine reuptake,
Aizheimer’s disease –
- senile dementia,
- caused by a decrease of Ach secreting neurons.

Myasthenia gravis –
weakness of skeletal muscles results from a reduction of Ach receptors.
Caused by autoimmune disease
Neostigmine
A drug used in myasthenia gravis.
Inhibits acetylcholine breakdown and increase the amount of available Acetylcholine

What is antigen?
Each toxin or organism contain chemical compound its makeup.
Can initiate acquired immunity.
Most of them are large polysaccharides.
With higher molecular weight - >8000
Has stereochemical character – epitopes – regularly occurring molecular group.

Heptens
Heptens – Molecular weight is low.
Heptens combined with protein and initiate response.

Lymphocyte clones
When antigen contact with lymphocyte only certain lymphocyte activate.
Activated B and T lymphocytes are highly specific for targeted antigen.
Lymphocyte that can produce one B and T specific cells – clone of lymphocytes
Millions of different lymphocytes store in bone marrow capable of producing highly specific B lymphocyte and T lymphocytes.

Origin of Clones
‘Gene segments’ are responsible to produce specific B cells (antibody) and T-cells quality.
These segment can mixed between genes and produce million – billion possible combination .
These combination will produce different type of B cells (antibody) and T-cells.

Activation of a clone
Each B cell has about 100,000 antibody molecules.
Each react only When high specific antigen contact with them.
Then activate long process of producing highly specific antibody.
In T cell, same happen – has surface receptor proteins.

Macrophage helps…..
Macrophage phagocytes most invading organism – partly digest.
Antigenic products are inside cytosol.
Antigen pass to lymphocyte by cell to cell contact.
In additionally, secrete Interleukin-I - promote growth of specific lymphocyte.

Memory cells
Few lymphoblast form by activating B-lymphocyte clone make different B-lymphocyte – memory cells.
Dormant like original clone.
When there is next expose they activate very quickly and overcome antigen.

Leading to virilization - the clitoris of girls is enlarged - Female pseudohermaphroditism.
Prepubertal male - rapid development male sexual organs.
Postpubertal male - difficult to diagnosis.

Protein bound fraction is low.
Aldosterone metabolized to glucuronide derivitatives.
Most in live and some in kidney.
These glucuronide can be converted back to aldosterone by acid pH.
Effects of Aldosterone
Na + reabsorption in urine, sweat, saliva and GIT.
Glucocorticoids can not act on minieralocoticoids receptor since the effect of enzyme 11ß-hydroxysteroid dehydrogenase type-2.
If the enzyme is inhibited/absent cortisol act as mineralocorticoid – apparent mineralocorticoid excess. (AME)

Hyperaldosteronism Can be
Primary Hyperaldosteronism –tumor in zona glomerulosa- conn’s syndrome.
Secondary Hyperaldosteronism - high renin activity in cirrhosis, heart failure, nephrosis.

Increase aldosterone secretion –
Na+ retention and K+ depletion
Hypertension, weakness, tetany, polyuria….

Destroy the adrenal cortex – primary adrenal insufficiency.
Can be autoimmune effect or after TB.
Hypotension, hypoglycemia with fasting, stress can make patient collapse.
Increase ACTH level make pigmentation due to MSH effect of ACTH.
Addisonian crisis can occur – dehydration, low blood pressure, loss of consciousness.

Cortisol deficiency and lead to increase ACTH secretion.
Several types.
‘Cholesterol desmolase’ deficiency is fatal in fetus due inability to make progesterone by placenta.
Congenital enzyme deficiencies

Mutation of gene for ‘steroidogenic acute regulatory protein’ makes adrenal hyperplasia in new born (Placental hormone normal).
Accumulation of lipids in the gland, called ‘congenital lipid adrenal hyperplasia’.
Female genitalia develop regard less of genetic sex since androgens are not form
17alpha-hydroxylase deficiency - sex hormone production affect so female genitalia will develop.
Adrenogenital syndrome
Adrenogenital syndrome - Deficiency of the enzyme 21-hydroxylase of 95% of affected patients.
Adrenal glands overproduce certain intermediary hormones which have testosterone-like effects on the fetus and child.
About 75% of affected infants have the “salt-losing” form of the disorder – mineralocorticoid deficient
Severe deficiency is fatal.

Condition/the clinical picture due to
excess of cortisol production.
excessive use of cortisol or other similar steroid (glucocorticoid).
It can be
ACTH independent – adrenal tumors, prolong use as a treatment.
ACTH dependent – ACTH secreting tumors –Anterior pituitary (Cushing’s disease), Lungs etc.

Fat redistribution
Upper-body obesity, rounded face, increased fat around the neck – ‘buffalo hump’.
Thinning arms and legs.
Excess protein catabolism
Skin becomes fragile, thin.
Poor wounds healing, bruises easily.
Hair is thing.
Bones are weakened – osteoporosis - backaches, rib and spinal column fractures.
weak muscles.
Precipitate insulin-resistant diabetes
Amino acid from protein catabolism convert to glucose.
Decrease peripheral utility of glucose.

Mineralocorticoid effect – cortisol has mineralocorticoid action as well.
Salt and water retention.
Hypertension
K+ depletion and weakness.

Can produce mental changes – increased appetite, insomnia, euphoria……. Psychoses.
Acne
Irregular or stopped menstrual periods in females.
Erectile dysfunction in males.

Major androgen is dehydroepiandrosterone.
The rest are adrostenedione and testosterone.
Estrogens & testosteron form in the circulation from Adrostenedione.

17-ketosteroid is formed and excreted with urine.
Two-third of urinary ketosteroids in man come from adrenal + liver. Only rest from testes.
Adrenal androgens are regulated by ACTH, not by gonadotropins.
Effect of androgen
Testosterone from testes is the most active androgen.
Adrenal androgens are 20% active as testicular androgen.
Adrenal androgens in normal concentrations has very little masculinizing effect.
In excessive amount make masculinizing effects.
Effect of androgen
Excessive secretion make masculinization.
Prepubertal boy – precocious pseudopuberty.
Adult male – accentuate existing characteristics.
Female – pseudohermaphroditism, adrenogenital syndrome.

Angiotensin II –
Act on synthesis of aldosterone.
No effect on cortisol.
In hemorrhage, standing, constriction of inferior vena cava, restriction of Na+ intake increase aldosterone secretion with renin-angiotensin pathway.

Plasma aldosterone is high when working in upright position due to
renin effect of postural.
decrease removal by the liver.
Those who confined to bed show circadian rhythm – high in early morning.
ANP – decrease responsiveness of Zona glomerulosa to angiotensin II.