GRUPO 1APLICACIÓN DE LA BIOQUIMICA A LA FISIOLOGIA

INTEGRANTES:

1. CARRIÓN ARCELA JEAN PIERRE

2. CASTRO MALDONADO BETTY

3. GASCO ARTEAGA LESLIE

4. GONZALES VASQUEZ DEYSI.

5. MENDOZA CASTILLO ALDO FABRIZIO

6. MORENO VASQUEZ LUIGUI.

CURSO: INGLES MÉDICO

DOCENTE: ROSA LLONTOP V.

CICLO: 2011-I

UNIVERSIDAD NACIONAL PEDRO RUIZ GALLO

FACULTAD DE MEDICINA HUMANA

It biochemistry is a science that studies the chemical composition of living organisms, especially proteins, carbohydrates, lipids and nucleic acids, as well as other small molecules present in the cells and chemical reactions with these compounds (metabolism) enabling them to obtain energy (catabolism) and generate own biomolecules (anabolism). Biochemistry is based on the concept that all living beings contains carbon and overall biological molecules are mainly composed of carbon, hydrogen, oxygen, nitrogen, phosphorus and sulfhide. It is the science that studies the chemical basis of life: molecules that compose the tissues, and cells that It catalyses the chemical reactions of metabolism such as digestion, photosynthesis and immunity, among many other things.

We can understand biochemistry as a discipline scientific integrative which deals with the study of biomolecules and Biosystems. It integrates this way physical-chemist laws and biological evolution which affect the Biosystems and their components. It does so from a molecular point of view and tries to understand and apply their knowledge to large segments of the medicine (gene therapy and biomedicine), agri-food, the farmacology.

Biochemistry is a cornerstone of the biotechnology and has established itself as a key discipline to tackle the major problems and diseases present and the future, such as climate change, the scarcity of agri-food resources to world population growth, depletion of fossil fuel reserves, the emergence of new forms of allergies, cancers increased, genetic diseases, and the obesity.

 Biochemistry is an experimental science and therefore shall have recourse to the use of numerous instrumental techniques and other fields, but the basis for its development is based on the fact that occurs in vivo at the sub-cellular level is maintained or preserved after subcellular fractionation, and from there, can study it and draw conclusions.

BIOCHEMISTRY IS THE SCIENCE THAT STUDENT LOS BEINGS ALIVE A LEVEL

MOLECULAR THROUGH TECHNIQUES AND METHODS PHYSICAL, CHEMICAL AND

BIOLOGICAL.

IT HAS AS OBJECTIVE KNOWLEDGE OF THE MATTER ALIVE AND SEARCH

ESTABLISH LAWS THAT GOVERNED THE VITAL PROCESSES FOR REGURLAR

MOLECULAR UNESCO AND PLAY THEM IN ARTIFICIAL CONDITIONS.

THE OBJECT D EESTUDIO D ELA BIOCHEMISTRY ARE SUBSTANCES THAT

CONSTITUTE E, HUMAN BODY.

GENDERED DIVISION OF THE BIOCHEMISTRY

STRUCTURAL CHEMISTRY: COMPONENTS D ELA ON VIVA AND THE BIOLOGICAL RELATIONSHIP WITH THE CHEMICAL STRUCTURE.

METABOLISM: ALL OF THE CHEMICAL REACTIONS THAT OCCUR

MOLECULAR GENETICS: KNOW THE HEREDITY AND VARIATION.

THE BIOCHEMISTRY SUCH AS SCIENCE

BIOQUIMICA

QUIMICA ORGANICA

BIOFISICA

FISIOLOGIA

BIOLOGIAINVESTIGACIÒN MEDICA

GENETICA

NUTRICION

PROCESS AT THE TISSUE LEVEL AND OF AGENCIES

TECHNIQUES FOR PHYSICAL PROPERTIES BIOQUIMICAS

PROPERTIES BIOMOLECULES

METABOLISM HEALTH

MECHANISM OF IDENTITY BIOCHEMISTRY

PROCESS AT THE TISSUE LEVEL AND OF AGENCIES

IMPORTANCE OF BIOCHEMISTRY IN HEALTH

ALL OF THE DISEASES HAVE MOLECULAR COMPONENT EXCEPT THE TRAUMÀTICAS.

THE MODERN METHODS HAS SETTLED THE BASIS OF MOLECULAR PATHOLOGY

Biochemistry

I .- DEFINITION: The science that studies the chemical basis of life : the molecules that comprise cells and tissues , that catalyze chemical reactions of cellular metabolism such as digestion , the photosynthesis and immunity , among other things.

We can understand the biochemistry as a scientific discipline that deals with integrating the study of biomolecules and biosystems. Thus integrates chemical and physical laws and biological evolution affecting the whole ecosystem and its components. It does from a molecular standpoint and tries to understand and apply their knowledge to broad sectors of medicine (gene therapy and Biomedicine ), pharmacology. 

II. - IMPORTANT: As noted above, the biochemical understanding the molecular basis of the chemical processes taking place in person beings, and especially in humans. Knowledge of these processes requires not only knowing the chemical composition of the body but the transformations that occur in the same and the principles that control them. The recognition that virtually all diseases have a molecular component, with the exception of the traumatic, causes the diagnostic and therapeutic methods used in medicine are undergoing a revolution, settling the foundations of molecular pathology.  These biochemical techniques to detect bacteria and viruses, before the appearance of antibodies, diagnose and prevent birth defects, making chemotherapy treatments and monitoring by detecting and amplifying cancer cells, these are just some of the profits of the biochemical the Health Sciences. 

THE FAST AND BIOCHEMISTRY PHYSIOLOGY

1. - What happens when you deprive an organism of caloric intake? 

Previously, we discuss in brief the metabolism of human body when it receives the normal caloric intake. This contribution is based on the so-called immediate early 3: Carbohydrates (sugars and carbohydrates), lipids (fats) and proteins.

They are also necessary salts and vitamins. These vital substances are absorbed differently through our digestive tract, transported by the blood, they will reach a unique process called the Krebs cycle, from which will be transformed into energy needed for our body.

But what happens when there are no calories? Let's see how the organism lives of their reserves and how these reserves leads to the aforementioned cycle for there to be transformed into energy needed for survival. 

2. - What are the body's reserves? 

The first fact we notice is that the body has reserves. Some say these are measured by weight. A man of about 70 kg. and 1.70 m. high, immediate early reservations are: 

- Glucose: 300 gr. (4 cal / gr.) = 1,200 Kcal. Last 24 hours.

- Fat: 10 to 11 kg. (9 cal / gr.) = 100,000 Kcal. They last longer than 40 days

- Protein: 10.5 kg. (4 Cal / g) = 45,000 Kcal.  In the fast eat the own reserves. The main source of energy is fat. Its advantages over sugars and proteas are:

Its caloric value is 9 kcal / g, so lasts longer and takes up less volume. It is stored without retaining water.

BIOCHEMISTRY OF THE FAST AND THE ROLE OF HORMONAL PHYSIOLOGY

1.- What are the stages of fasting?

Depending on whether one or other immediate principle, as the main source of energy during fasting, it can be divided into three distinct phases as detailed below. 

FIRST PHASE:

The main fuel is glucose and all sugars and carbohydrates. First circulating glucose is consumed and then do the liver glycogen and muscle. In the biochemical process:

1 º. Glucose is stored in liver and muscle.

2 º. Out of there.

With all this glucose, the circulating and stored, we can spend 24 to 48 hours, after which time there will be gaps and go into hypoglycemia. Symptoms of hypoglycemia are: fatigue, dizziness, cold sweats, etc. The subject at this stage tends to lose weight. 

Metabolism of carbohydrates:

The decreases in fasting blood glucose, reaching a plateau around the third day. The fall is due to depletion of liver glycogen and gluconeogenesis delay. With the continuation of the fast there are several mechanisms by which glucose is normalized:

1) The tissues more easily metabolize fatty acids and ketone bodies. 2) It enhances gluconeogenesis, producing 30 to 35 gr. carbohydrates daily coming from amino acids and glycerol. 

In the early days of fasting glucose is primarily directed to the central nervous system. When the supply begins to decline, it triggered a series of compensatory mechanisms. The most important is the increase in sympathetic nervous system activity, resulting in an increased release of catecholamine’s, which allows glucose to supply the central nervous system through other means. Then the central nervous system use the fat burning products, acetoacetic and beta-hydroxybutyric acid. 

SECOND PHASE:

The entry of the organism in hypoglycemia marks the second phase of fasting, characterized by the consumption of fat. Hypoglycemia is the same in charge of implementing the mechanisms that direct consumption of fat in this Phase 2 and will act on the hypothalamus, nerve endings, adrenal and pancreas. 

Hypothalamus:

By acting on it will get to release their stimulating factors, which will by-pituitary portal system to the adenohypophysis, it will release the following factors or hormones: 

a) Somatotropic or growth hormone (STH):

- Prevents glucose is consumed by the cells. It ishyperglycemic. She has a lipolytic action (is what interests us). Is lipolytic, diabetogenic and ketogenic by its action on proteins during fasting and is postulated to have a dominant protective role in metabolism. 

b) ACTH or ACTH: It acts somewhat in the previous stage producing phosphorylase and this in turn, glycogenolysis (glycogen strand breaks) and formation of glucose-6-phosphate.

c) Cortisol: Its main functions are to increase the level of blood sugar through gluconeogenesis to suppress the immune system and help the metabolism of fats , proteins and carbohydrates 

d) TSH: Lowers insulin. 

e) ADRENAL GLANDS: 

Increased Catecholamines:

Adrenaline and noradrenaline that under normal conditions stimulate gluconeogenesis in the liver and muscle, inhibit the uptake of glucose in the muscle increases in adipose tissue and decreases insulin secretion induced by glucose.

Fasting is observed rise in urinary excretion of adrenaline, noradrenaline and vanillic acid-mandelic, less marked in obese than in normal weight individuals.

During fasting, the increase depends on the possible decrease in plasma volume and extracellular fluid caused by the loss of sodium and water.

Inhibit glucose uptake at the level of muscle (which also acted as in the previous phase). They emphasize the lipolysis in adipose tissue. 

Increased glucocorticoid:

Accelerate the release of amino acids from proteins, both the liver and extrahepatic tissues. Accentuate the amino acid uptake by the liver.

Increase the activity of fructose diphosphate-phosphatase and thus the transformation of fructose 1-6 diphosphate ester ester-fructose-6-phosphate.

Stimulate the activity of glucose-6-phosphatase at the level of liver and, therefore, the gluconeogenesis. This is important to explain later why the brain survives despite not having their favorite food, glucose. 

f) Pancreas:

Decreases insulin antilipolytic hormone considered, and increases glucagon.

Insulin: Decreases progressively after the third day and remains at a low plateau, it has been associated with a likely increase in peripheral resistance, possibly linked to the behavior of the STH.   Glucagon:

This hormone is responsible in part for the stimulation of glycogenolysis, ketogenesis and mild hepatic proteolysis. It also decreases the intensity of the oxidation of glucose. Is lipolytic in adipose tissue and its action on pancreatic insulin release facilitates the cells. It is thought that glucagon is responsible for the observed significant increase in blood levels of adrenaline and noradrenaline.

The initial hypoglycemia in turn stimulating glucagon, leading to an intensification of this action. In the fasting values increase to almost double in the third day, then facilitating the provision of glucose by the liver gluconeogenesis, and decreased slowly until numbers equal to or slightly higher than the previous fasting. 

The lipolyticaction of these hormones results in increased free fatty acids, these results in two physiological facts:

- Decrease in respiratory quotient.

- Development of ketosis, which is usually an almost constant feature in this 2nd stage of fasting. 

Fat metabolism: fasting, adipose tissue triglycerides are catalyzed steadily, releasing fatty acids into plasma. As this amount exceeds regarding the need of the body, a portion of free fatty acids is used as the primary source of heat and power and the

other is metabolized in the liver, where those are converted into acetyl-coenzyme A, which in turn can follow three paths:

Entering the Krebs cycle. Be used for synthesis of substances that are part of the plasma triglycerides and

endogenous cholesterol. Transform into ketone bodies, which are the other major source of energy in

fasting.  During fasting is restricted the supply of glucose and consequently, the first two

roads are partially blocked and the majority of acetyl-coenzyme A is converted into ketone bodies that, passing into the blood, leading to a state of metabolic acidosis. Ketone bodies are in turn three ways:

1)They cover the metabolic requirements (most important).

2)They are eliminated in urine and minimally

3)They are eliminated by the lungs. 

Moreover, in this second phase, the entire body undergoes a process of adaptation to fasting. In this adaptation are given:

a) Decreased basal metabolism:

- A quick step metabolic reduction.

- A slow step preceded by, or accompanying weight loss.

b) Reduction of physical activity. The body has less weight and less work. 

THIRD PHASE:

It can’t be considered as fast, for reaching this stage again and appetite to eat.  If not, enter the process called "half past acute" or starvation, and this is an irreversible path toward death.

At this stage the body, which has burned nearly all its reserves, will begin to consume the protein that are essential for life.

One of the signs that are in the clinic at this stage is swelling. It is mainly caused by decreased plasma oncotic pressure, maintained primarily by the amount of albumin is in it and that is burned as fuel for the body.

The appearance of these edema, usually usuallyaAnaxarchus (ie, generalized edema), is a sign that we are in this 3rd stage of fasting and a dangerous stage of life, since the mechanisms of compensation organism are being forced beyond their means. 

PHYSIOLOGICAL CONSTANTS: ITS CHANGES DURING FASTING

1 .- PLASMA:

The water loss during fasting results in a slight decrease in blood volume during the first 10 to 15 days. 

1.1. - Red blood cells

Relatively, the hematocrit slowly increased until the tenth day, the same as the cell volume, then continues. Some authors observed a decrease in hematocrit without logical explanation. Others claim a reduction due to losses of vitamins and iron. 

1.2.-Leukocytes:

There is an initial increase probably due to the decrease in plasma volume. After surviving 10 days neutropenia from 20 to 50% from baseline. The decline would be caused by bone marrow depression due to protein catabolism or perhaps by circulatory factors. However, the response to infection is normal and independent of the duration of fasting. 

1.3.-Plasma sodium: At first the sodium enters the cells accompanied by water. After normalization occurs during the period of fasting. Serum sodium decreased in the first days of a frank, then, remains normal or slightly decreased. Sodium losses are mainly via the urinary, digestive, skin and extracellular accumulation. In conclusion, the severe sodium spoliation fasting is always or almost always, secondary, or a therapeutic error. It should also be aware that sodium loss is never isolated, but is often accompanied by other electrolytes. 

1.4 .- Plasma potassium:The values found in blood are slightly contradictory, the small fraction of averages of the serum potassium 4.6 mg. says it has little value demonstration of what happens to the total organic potassium.

Loss: potassium transcellular fluid passes and is then excreted in urine up to 40 mg / day in the first week, then maintained an average of 10 to 15 mg / day. In the first week, many different factors come together so that there is depletion: 

A) Increased gluconeogenesis by excessive initial use of lean mass, and this is associated with a loss of nitrogen in urine and subsequent loss of 2 mg. K / g N.

B) Action of aldosterone and sodium and facilitator-saving loss of potassium.

C) Initial Polyuria: apparently the greatest loss of potassium occurs at 1 day of fasting.

D) Release of intracellular water, which is accompanied by potassium, the most important cation.

E) Cellular release of potassium in most of the tissue that is catabolized. 

1.5.-Plasma calcium: the calcium level doesn’t have major variations. 

1.6.-Magnesium is primarily an intracellular ion on the great controversies exist regarding its role in metabolism and the effects of their loss. It describes numerous confounding due to its depletion, which we have not observed in fasting. 

1.7.-Chlorine: low urinary excretion by 13% until the third day of fasting rapidly and then tends to normalize. 

1.8.-Aldosterone: Its hepatic conjugation and renal excretion decreased, while its secretion increases in sequence to the loss of initial partner in fasting. Renin increases, stimulating the formation of aldosterone, but not optimally, it is a glucose-dependent mechanism. The increase is almost double in the first week. 

1.9.-Thyroid function: Studies have shown decreased thyroid function by the results of iodine 131 uptake and PBI.

1.10 .- Hydroxyproline:It is a product of the catabolism of collagen, whose elimination in the urine can be considered as an index for metabolic studies of bone tissue. There is a progressive increase in the elimination of hydroxyproline in urine. This would be related to acidosis, phosphorus depletion, and changes in the secretion of thyroid hormone, parathyroid and STH. The loss may be partly corrected by administering potassium. 

1.11 .- Bilirubin: There is an increase of bilirubin in obese and normal liver function even in those with pathology. The increase, reaching three times the basal one, is established in the initial two or three days and then decreases maintaining about twice the first value. 

1.12 .- GPT transaminases and alkaline phosphatase, GPT, GOT maintain their values, whereas the alkaline phosphatase decreased slowly during the period of fasting.

BIOCHEMISTRY AND PHYSIOLOGY OF THE ADRENAL CORTEX

All steroid hormones contain a basic structure that corresponds to the core of ciclopentanoperhidrofenantreno (same cholesterol) steroids with 21 carbons (C21) have glucocorticoid and mineralocorticoid properties. The adrenal cortex is able to synthesize glucocorticoids (cortisol), mineralocorticoids (aldosterone) and adrenal androgens (dehydroepiandrosterone).

The adrenal cortex is divided into zones that synthesize these hormones specific and depends on the activity and activation of different enzymes contained in each of the zones. The outermost zone called glomerulosa produces aldosterone and mainly inland areas, fasciculata and reticular produce cortisol and androgens.

Transport of steroids

Cortisol circulates bound to proteins and less than 5% in free form in plasma. The protein bound fraction is bound to cortisol binding globulin (CBG) and albumin. Protein-bound fractions can be released into the tissues to maintain a readily available reserve pool. Like other hormonal systems elevated cortisol binding globulin or CBG (eg oral estrogen use) increases the total plasma cortisol concentration although the proportion of free cortisol remains normal. Many of the synthetic steroids bind less efficiently to CBG, and this may explain the ease with which some synthetic analogs effects of overdose (Cushing syndrome), even using low doses. Cortisol metabolites are biologically inactive and bind weakly to circulating plasma proteins. Aldosterone also

binds to plasma proteins but at a much lower than cortisol. Glucocorticoids and especially cortisol are secreted with a marked circadian rhythm having a morning peak, a decrease to a nadir noon and evening or night. The daily amount of secretion of cortisol ranges between 15 and 30 mg. The inactivation of steroids in general is produced in the liver where they undergo a reduction of one ring and subsequent conjugation with glucuronic acid. The term applies to all glucocorticoid adrenal steroids that will have action primarily in intermediary metabolism. The principal glucocorticoid is cortisol or hydrocortisone. Mineralocorticoids are steroids related to sodium and water retention, the most important being aldosterone.

Mechanism of action of cortisol

Cortisol enters the target cell by diffusion and binds to its receptor, binding to specific sites in the DNA, resulting in increased synthesis of RNA and proteins according to the type of target cell. Thus the physiological actions of glucocorticoids include regulation of protein synthesis, metabolism of proteins, carbohydrates, lipids and nucleic acids.

• Carbohydrate metabolism: Glucocorticoids increase glucose acting as an antagonist of insulin and suppress insulin secretion. Thus inhibit the uptake of glucose by peripheral tissues and promote gluconeogenesis.

• Protein metabolism: it produces a catabolic with increased protein destruction and excretion of nitrogen.

• Glucocorticoids increase liver glycogen and promotes gluconeogenesis, causing a mobilization of glycogenic amino acids that come from supporting structures such as muscle, skin, bone and connective tissue, also inhibit protein synthesis and amino acid uptake.

• Fatty acids: Glucocorticoids regulate fatty acid mobilization lipase producing cell activation.

Glucocorticoids have anti-inflammatory properties are probably related to their actions on the territory of microvascular and cellular effects. Cortisol maintains normal vascular response to vasoconstrictor factors and opposes increases capillary permeability characteristic of acute inflammation. Also induces an increase in polymorphonuclear leukocytes, causes disappearance of circulating eosinophils decreases the activity of T lymphocytes Cortisol in this way alters the cellular and humoral immunity. In addition, glucocorticoids inhibit the production and / or the action of local mediators of inflammation such as lymphokines and prostaglandins.

The cortisol response in minutes to a variety of physical and psychological stress (trauma, surgery, exercise, anxiety, depression). Hypoglycemia and fever are also potent stimuli for the secretion of ACTH and consequently cortisol.

Other effects

Although cortisol is predominantly a glucocorticoid, mineralocorticoid has an effect when it exists in high concentrations. Contributes to the maintenance of extracellular volume and causes mild salt and water retention. Besides sensitizing arterioles to the action of vasoconstriction such as adrenaline, the latest conditions promote the onset of hypertension when there is excess of glucocorticoids.

Regulation of cortisol secretion

ACTH produced by the anterior pituitary gland controls the activity of the reticular zone and faciculada. Specifically, ACTH stimulates cortisol production by increasing the breakdown of the side chain of cholesterol to form pregnenolone, this is the limiting step of the synthesis of cortisol. The action of ACTH is rapid, and its effect can be seen within 5 minutes of an acute increase in ACTH. In addition to this acute effect and a

continued increase in high doses of ACTH induce hyperplasia of the adrenal cortex cells. In contrast to this the absence of hypothalamic pituitary ACTH pathology will lead to atrophy of the areas and reticular faciculada confirming that ACTH exerts a trophic effect on the fabric. Within the regulation of steroid production there is negative feed back of cortisol on ACTH secretion. This effect is exerted at both hypothalamic (decreases the release of CRH or directly on the pituitary ACTH decreasing.

The CRH and ACTH secretion follow a circadian rhythm that works according to the sleep-wake cycles. Thus we see that the concentration of cortisol in human plasma low around midnight and rises to a maximum peak at around 8 am, then there is a fall throughout the day. Superimposed on these trends, there are episodic releases a few minutes of cortisol in response to various circumstances such as stress.

Because of circadian variations and the possibility of peak cortisol secretion during the day of cortisol measurement alone can not be interpreted without the information on the sampling. That is why measuring the integrated secretion of corticosteroids may better reflect the clinical status of a patient. Repeated measurements may also be trying to assess the presence or absence of normal cricadiano pace. 

Pathophysiology of glucocorticoid production

Excess cortisol

Excessive production of cortisol may be the result of an overproduction of CRH, ACTH or adrenal tumors that produce cortisol. All causes of endogenous hypercortisolism (produced by the adrenal glands of the patient) or exogenous (drug use) are called "Cushing's syndrome." The term "Cushing's disease" is reserved for cases where the

origin is in an ACTH-producing pituitary tumor.

The metabolic effects of glucocorticoid excess are:

1. Increased gluconeogenesis and insulin resistance, this can lead to diabetes mellitus 2. Increased protein catabolism, this can lead to wasting, osteoporosis and thinning of the skin.

3. Increase and redistribution of body fat: obesity occurs predominantly a central moon facie, tung or dorsal fat accumulation, maintaining relatively slender limbs.

4. Involution of lymphoid tissue and decrease the inflammatory response: there is a decrease of cellular and humoral immunity which increases susceptibility to infection.

5. Increased secretion of acid by the stomach which leads to a predisposition to peptic ulcer.

6. Sodium retention and redistribution of body fluids leading to edema and hypertension.

7. Gonadal function: Glucocorticoids affect gonadotropin secretion. In men, testosterone levels decrease. In women, suppresses LH response to GnRH, leading to a

suppression of the secretion of estrogens and progestins with anovulation and amenorrhoea.

All previously listed effects occur independent of the source of glucocorticoids. The most common cause of Cushing's syndrome due to exogenous administration of pharmacological doses of these general purpose anti-inflammatory and immunosuppressive

Adrenal androgens

The zona reticularis of the adrenal cortex produces adrenal androgens (dehydroepiandrosterone sulfate (DHEAS) and androstenedione). The role of sex steroids is not entirely clear. He knows his importance in the sexual body hair growth in women (axillary and genital), but it is unclear the role in men. The secretion of these steroids is started just before puberty in normal children it is called adrenarche. Contribute to the growth spurt at this stage of childhood and puberty and appear to be necessary for the development of axillary and pubic hair and the onset of sweat gland secretion.

Androgen Excess

Can occur from androgen-producing adrenal tumor or as a result of hyperstimulation of the entire adrenal cortex by ACTH.

In men, the clinical manifestations are often not evident because the rate of testicular testosterone production is significantly more important. In women, however, excess androgens cause adrenal origin varying degrees of hirsutism or virilization.

Glucocorticoid insufficiency

Causes

1. Primary: involve failure of the adrenal glands: Addison's disease

a. Destruction of the gland autoimmune and inflammatory diseases (tuberculosis, hemorrhage)

b. Resection of both adrenals.

2. Secondary: absence of ACTH, pituitary failure.

3. Tertiary: the absence of CRH, hypothalamic failure.

There may be atrophy "functional" for example, after long time of exogenous steroid treatment, the gland, having no stimulation of ACTH (which is suppressed by the presence of exogenous corticosteroids) and suspension of them.

To have a deficit of glucocorticoids is needed more than 90% of both adrenal cortices damaged. Depending on the cause this damage can be gradual (eg autoimmune diseases) or acute (surgical resection or bilateral adrenal hemorrhage).

If the phenomenon is gradual, the first stage, we have a sufficient baseline secretion but opposite stress requiring increased glucocorticoid secretion gland will not be able to respond. This is called decreased adrenal reserve. When the disease progresses or in cases of acute destruction of the gland basal secretion of steroids will be altered and will remain, leading to adrenocortical insufficiency.

If the disease is primary, try to compensate by increasing pituitary secretion of ACTH which will result in the patient hyperpigmentation. Obviously this will not happen if the failure is secondary or tertiary education.

In the primary causes, symptoms usually associated with glucocorticoid deficiency and mineralocorticoid deficiency (see below).

Symptoms of adrenal insufficiency:

• Hypotension: by decreasing sodium retention.

• Hyponatremia and hyperkalemia, especially motivated by the mineralocorticoid deficiency.

• General symptoms: weakness, fatigue, anorexia, vomiting, weight loss.

• Hyperpigmentation: only in cases of primary adrenal failure involving increased secretion of ACTH and melanocyte stimulating hormone concomitantly.

Mineralocorticoids

The zona glomerulosa of the adrenal gland produces mineralocorticoids being more powerful and important of these aldosterone. The main site of action of aldosterone is the distal tubule and collecting the kidney, where an increase in sodium reabsorption and increases excretion of potassium and hydrogen. Sodium reabsorption is coupled to the secretion of potassium and hydrogen ions. This leads to aldosterone causes increased blood pressure partly by an increase in plasma volume and by an increased sensitivity of the muscles of the arterioles.

Renin-angiotensin-aldosterone

The renin angiotensin system is the most important regulator of the secretion of aldosterone, the aldosterone response to ACTH secretion, but the renin-angiotensin system predominates in the regulation of blood pressure and salt retention.

Renin is a proteolytic enzyme that is secreted by the juxtaglomerular cells of the region of the nephrons in the kidney. The release of renin into the plasma occurs when the juxtaglomerular region detects hypotension or renal ischemia. Renin exerts its proteolytic action on angiotensinogen, this is an alpha 2 globulin produced in the liver. Renin angiotensinogen breaks converted to angiotensin I which is biologically inactive but which in turn is converted into different tissues to angiotensin II, the latter is the most powerful pressor substance known. Angiotensin II causes an increase in systolic and diastolic pressures. The main site of conversion of angiotensin I to angiotensin II are pulmonary endothelial cells. Under normal conditions the limiting step for the production of angiotensin II is the amount of renin available.

In addition to its role vasoconstrictor, angiotensin II acts directly on the zona glomerulosa of the adrenal cortex to stimulate aldosterone secretion. What happens with particular intensity when there is depletion of salt.

Regulation of renin production:

1. Sympathetic stimuli reaching the juxtaglomerular apparatus

2. Sodium flow through the macula densa of the distal tubule: when the flow of sodium is high, renin secretion is suppressed.

3. Transmural pressure: When blood pressure is elevated renin secretion is suppressed. The plasma

potassium concentration also has a weak effect on renin production. Hypokalemia tends to increase its secretion, but paradoxically the hypokalemia decreases the secretion of aldosterone.

Regulation of aldosterone

Aldosterone secretion is dependent on the concentration of angiotensin II, plasma potassium and ACTH, these three elements can directly stimulate aldosterone secretion. The primary regulator of aldosterone is the plasma volume and this effect is accomplished through the renin-angiotensin system that can overcome the changes supposedly induced by potassium or ACTH. Only potassium normovolemia conditions may regulate the secretion of aldosterone. The same goes for ACTH. ACTH secretion chronic fails to maintain an overproduction of aldosterone and the mechanisms of the renin-angiotensin system produced an escape from this regulation.

Pathophysiology of mineralocorticoid excess

There may be an excess secretion of aldosterone by the following reasons:

• Aldosterone producing tumor or hyperplasia of the adrenal glomerulosa region primary.

• Hyperactivity of the renin angiotensin

• Hypokalemia

Effect of mineralocorticoid deficiency

Symptoms resulting from mineralocorticoid deficiency is associated depend on whether or not a deficit of other steroids in the adrenal cortex.

Directly resulting from mineralocorticoid deficiency includes hypertension, hyponatremia and hyperkalemia.