Hormones Secreted By Kidney, Heart, GIT

INTRODUCTION OF GLAND:

ENDOCRINE GLAND:

Endocrine glands are ductless glands of the endocrine system that secrete their products, hormones, directly into the blood. The major glands of the endocrine system include the pineal gland, pituitary gland, pancreas, ovaries, testes, thyroid gland, parathyroid gland, hypothalamus and adrenal glands. The hypothalamus and pituitary gland are neuroendocrine organs.

 

HORMONES SECRETED BY GLAND:

KIDNEY:

The kidneys produce three important hormones: erythropoietin, calcitriol (1,25- dihydroxycholecalciferol ) and renin. They also synthesize prostaglandins, which affect many processes in the kidneys .

ERYTHROPOIETIN:

INTRODUCTION OF ERYTHROPOIETIN:

Erythropoietin also known as haematopoietin or haemopoietin, is a glycoprotein cytokine secreted by the kidney in response to cellular hypoxia; it stimulates red blood cell production (erythropoiesis) in the bone marrow. 

PHYSIOLOGICAL ROLE :

Erythropoietin is essential to the production of red blood cells because it is required for survival, proliferation, and differentiation of erythroid progenitor cells in the bone marrow. In the later stages of erythrocyte differentiation, the receptor for erythropoietin is downregulated and the hormone no longer necessary for cell survival.

Red blood cells deliver oxygen to all tissues and when red cell numbers are reduced or abnormal - a condition called anemia - tissues are deprived of oxygen. Anemia can result from a broad range of problems, for example from hemorrhage, destruction of red cells due to autoimmunity, or interference with cell production associated with cancer chemotherapy. As depicted below, anemia leads to hypoxia within the kidney, which triggers additional interstitial cells there to start secreting erythropoietin. Increased secretion of erythropoietin enhances and accelerates the production of new red blood cells from their progenitors.

In addition to its effect on red blood cell production in the bone marrow, erythropoietin has been implicated in a number of other cellular effects in vasculature, heart, and nervous system. The importance of these other influences is poorly understood.

DISORDERS:

·       INTRODUCTION:

Individuals can suffer from having too much erythropoietin in the blood or from having an erythropoietin deficiency. 

·       CAUSE:

A common cause of erythropoietin deficiency is chronic kidney disease. When the kidneys are damaged, their ability to produce erythropoietin is compromised and anemia ensues.

·       SYMPTOMS:

Low red blood cell counts cause anemia; symptoms include fatigue, shortness of breath, increased heart rate, and dizziness.

·       TREATMENT:

Erythropoietin can be used to correct anemia by stimulating red blood cell production in the bone marrow in these conditions. The medication is known as epoetin alfa (Epogen, Procrit) or as darbepoietin alfa (Arnesp). It can be given as an injection intravenously (into a vein) or subcutaneously (under the skin).

·       AFFECTED POPULATION:

Mean age (± SD) was 53 ± 12 years and 50% were female. Median (IQR) erythropoietin concentrations were 7.6 (5.8–9.9) IU/L in men and 7.9 (6.0–10.6) IU/L in women. A strong positive correlation was found between erythropoietin and waist circumference, glucose and systolic blood pressure (all P < 0.05). In subjects with normal renal function there was a strong exponential relation between hemoglobin and erythropoietin, whereas in renal impairment (eGFR < 60 mL/min/1.73m^²) this relation was linear (men) or absent (women) (P < 0.001 for interaction). Single-nucleotide polymorphisms at the HBS1L-MYB locus were shown to be related to erythropoietin levels (P < 9x10^-21), more significantly than other erythrocyte parameters.

CALCITRIOL:

INTRODUCTION:

Calcitriol is synthetic  version  of  Vitamin D3 used to treat calcium deficiency with hypoparathyroidism (decreased functioning of the parathyroid glands) and metabolic bone disease in people with chronic kidney failure.

STRUCTURE:

PHYSIOLOGOCAL ROLE:

Calcitriol activation pathways and biological functions in target tissues. In human, vitamin D₃ is the predominant form of vitamin D, which is synthesized from 7- dehydrocholesterol upon sunlight exposure. Vitamin D may also be obtained from dietary sources or supplements as either vitamin D₂ or D₃. Vitamin D₃ binds to vitamin D-binding protein (DBP) in the bloodstream and then taken up within hours following synthesis or dietary uptake to be activated by liver and kidney. In the liver it is first converted by mitochondrial cytochrome P450 (CYP) enzyme CYP27A1, microsomal CYP2J3 and CYP2R1 to 25-hydroxyvitamin D. This molecule is further converted by the renal enzyme 1-a hydroxylase (CYP27B1) to 1,25 dihydroxycholecalciferol (calcitriol), which is the active form of vitamin D. Finally, calcitriol binds to intracellular vitamin D receptor (VDR) in most cells in the body by functioning both as a paracrine and an autocrine agent.

DISORDERS:

·       SYMPTOMS:

difficulty breathing; swelling of your face, lips, tongue, or throat.

·       TREATMENT:

Oral

·         Adult, Initial: 0.25 mcg orally once/day to every other day; titrate by 0.5-1 mcg/day every 4-8 weeks

·         Pediatric: 0.25-2 mcg/day orally once/day.

Intravenous (IV);

·         Initial: 1-2 mcg IV (0.02 mcg/kg) 3 times/week; adjust dose every 2-4 weeks

·         Maintenance: 0.5-4 mcg IV 3 times/week

RENIN:

INTRODUCTION:

Renin, also known as an angiotensinogenase, is an aspartic protease protein and enzyme secreted by the kidneys that participates in the body's renin–angiotensin–aldosterone system —also known as the renin–angiotensin–aldosterone axis—that mediates the volume of extracellular fluid and  atrial contrition.

STRUCTURE:

PHYSIOLOGICAL ROLE:

HEART:

The natriuretic peptide family consists of three biologically active peptides: atrial natriuretic peptide (ANP), brain (or B-type) natriuretic peptide (BNP), and C-type natriuretic peptide (CNP). Among these, ANP and BNP are secreted by the heart and act as cardiac hormones.

ATRIAL NATRIURETIC PEPTIDE (ANP):

INTRODUCTION:

The atrial natriuretic hormone (ANP) is a cardiac hormone which gene and receptors are widely present in the body. Its main function is to lower blood pressure and to control electrolyte homeostasis. Its main targets are the kidney and the cardiovascular system but ANP interacts with many other hormones in order to regulate their secretion.

STRUCTURE:

PHYSIOLOGICAL ROLE:

·         ANP stimulates vasodilation of the afferent arteriole of glomerulus: this results in increased renal blood flow and an increase in glomerular filtration rate. Increased glomerular filtration, coupled with inhibition of reabsorption, results in increases in excretion of water and urine volume - diuresis! It seems that in most cases, ANP also induced vasoconstriction in the efferent arteriole, which also increases glomerular filtrate volume.

·         ANP acts on several segments of the nephron - most notably the inner medullary collecting duct - to reduce reabsorption of sodium. If sodium reabsorption is inhibited, the sodium in filtrate is excreted in urine - naturesis! ANP also inhibits Na+/H+ exchange in the proximal tubule and Na+/Cl- reabsorption in the distal tubule, both of which enhance sodium excretion.

DISORDERS:

Low plasma levels of MR-ANP predict development of future diabetes and glucose progression over time, suggesting a causal role of ANP deficiency in diabetes development.

BRAIN NATRIURETIC PEPTIDE (BNP):

INTRODUCTION:

Brain natriuretic peptide (BNP) is a peptide hormone that is released in response to volume expansion and the increased wall stress of cardiac myocytes. BNP helps to promote diuresis, natriuresis, vasodilation of the systemic and pulmonary vasculature, and reduction of circulating levels of endothelin and aldosterone.

STRUCTURE:

PHYSIOLOGICAL ROLE:

In response to increased stretch or tension, left ventricular myocytes release BNP and N-terminal-pro-BNP (NT-pro-BNP) from precursors. BNP is an active molecule with a short plasma of BNP, with a longer half-life. It is primarily cleared by the kidneys. Reduced eGFR correlates to a greater extent with elevated plasma NT-pro-BNP than to BNP levels. Increased NT-pro-BNP/BNP ratio correlates with advancing CKD stages, especially if the eGFR is 30 mL/min per 1.73 m². However, both BNP and NT-pro-BNP are associated with surrogate and hard clinical outcomes in asymptomatic patients with CKD.

DISORDERS:

Obese patients have been shown to have lower natriuretic peptide levels 

SYMPTOMS

 clinical signs and symptoms of heart failure. Flash pulmonary edema.

 

GASTROINTESTINAL TRACT (GIT):

The gastrointestinal hormones (or gut hormones) constitute a group of hormones secreted by enteroendocrine cells in the stomach, pancreas, and small intestine that control various functions of the digestive organs. There are different hormones related to gastrointestinal system which plays important role in digestion of the food. These hormones are related to each other and in different pathological condition, their production may increase or decrease leading to derangement of digestive process. Some important hormones are Gastrin, Cholecystokinin (CCK), and Secretin.

GASTRIN:

INTRODUCTION:

Gastrin is peptide hormone produced by G cells (flask shaped cells), from the antrum of the stomach.  Also found in duodenum and jejunum.

STRUCTURE:

PHYSIOLOGICAL ROLE:

DISORDERS In the Zollinger–Ellison syndrome, gastrin is produced at excessive levels, often by a gastrinoma (gastrin-producing tumor, mostly benign) of the duodenum or the pancreas. . Additionally, elevated gastrin levels may be present in chronic gastritis resulting from H pylori infection.

SYMPTOMS;

·         Abdominal pain.

·         Diarrhea.

·         Burning, aching, gnawing or discomfort in your upper abdomen.

·         Acid reflux and heartburn.

·         Nausea and vomiting.

·         Bleeding in your digestive tract.

·         Unintended weight loss.

·         Decreased appetite.

AFFECTED POPULATION

Zollinger-Ellison syndrome is rare and only occurs in about one in every 1 million people. Although anyone can get Zollinger-Ellison syndrome, the disease is more common among men 30 to 50 years old. A child who has a parent with MEN1 is also at increased risk for Zollinger-Ellison syndrome.

CHOLECYSTOKININ (CCK);

INTRODUCTION:

Cholecystokinin is a peptide hormone of the gastrointestinal system responsible for stimulating the digestion of fat and protein. Cholecystokinin, officially called pancreozymin, is synthesized and secreted by enteroendocrine cells in the duodenum, the first segment of the small intestine.

STRUCTURE;

PHYSIOLOGICAL ROLE:

DISORDERS

Cholecystokinin deficiency has been described in humans as part of autoimmune polyglandular syndrome, characterized as a malabsorption syndrome clinically similar to pancreatic exocrine insufficiency

SYMPTOMS

Symptoms of this disorder may be shortness of breath, fatigue, weakness, rapid heartbeat, angina, anorexia, abdominal pain, indigestion, and possibly intermittent constipation and diarrhea

AFFECTED POPULATION

APECED occurs in about 1 in 90,000 to 200,000 people in most populationsstudied, which have been mainly in Europe. This condition occurs more frequently in certain populations, affecting about 1 in 9,000 to 25,000 people among Iranian Jews, Sardinians, and Finns.

SECTRETIN:

INTRODUCTION:

Secretin is a hormone that regulates water homeostasis throughout the body and influences the environment of the duodenum by regulating secretions in the stomach, pancreas, and liver. It is a peptide hormone produced in the S cells of the duodenum, which are located in the intestinal glands.

STRUCTURE:

PHYSIOLOGICAL ROLE;

DISORDERS

Secretin is also given by IV for pervasive developmental disorder (PDD), pancreatitis and other pancreas problems, overactive parathyroid gland, duodenal ulcers, bleeding in the stomach and intestines, and heart failure.

SYMPTOMS

Symptoms of PDD may include behavioral and communication problems such as: Difficulty using and understanding language. Difficulty relating to people, objects, and events; for example, lack of eye contact, pointing behavior, and lack of facial responses

Vitamin B1

Thiamine

Introduction

• In 1926 thiamine was first vitamin to isolated in pure form
•  Thiamine is heat-labile and water-soluble of vitamin B,it is also known as B₁
• It is also with antioxidant , erythropoietic,mood modulating and glucose regulating artirates
•  Thiamine perform carbohydrate metabolism function in both animals and plants by active form-, as a component of co-enzyme “thyamine pyrophosphate”.

Structure

Chemical name

 Chemically Thiamine is 2,5-dimethyl,4-methyl-6-amino pyrimidin 5-oh ethyl thiazole.

-          Vitamin B₁ is also known as  Thiamine, Its also spelled Thiamin.

-          Some chemical name and structure are follow

1.       Chemical name

Thiamine nitrate (salt) ,thiamine mono nitrate B₁ nitrate

2.     Molecular formula

     C₁₂H₁₇H₅N₅O₄S.

3.     Molecular weight

                              327.36 gm /mol

4.    Chemical name
- aneurine mononitrate
-aneurine nitrate
-betabian mononitrate
-thiazolium,3(4-amino-2-methyl-5-pyrimidinyl)
-vitanen
thiamine pyrophosphate(thiamine disphosphate)

Structure

Thiamine react with Adenosine triphosphate (ATP)to from an active co-enzyme thiamine phosphate (diphosphate)

The part of TPP  molecule that is most commonly involved in reaction is the thiazol ring, which contain nitrogen and sulphur.

Occurance and food sources

Plant sources

·         In creals,grains.

·         it is concentrated in outer germ / bran layers (e.g. : rice , polishing)

·         other good sources are peas , beans , whole creals  , grain , brans ,nuts ,prunes etc

Animal source

Thiamine is presnt in most animal tissues . liver , meat, and eggs supply considerable amounts . ham/pork meats are particularly rich , milk are low concentration , but a good source.

Storage

Thiamine is presnt in both kidneys , liver , skeletal muscle , and in brain .

·         the amount of thiamine in body approx. 25 mg.

Requirement

Benefits of thiamine

 

Recommended intake

·       Recomended dietry allowance(RDA)

Average daily level of intake sufficient to meet they nutrients requirement

·       Adequate intake

Intake at this level is assumed to ensure nutritianaladequency established when evidence is sufficient to develop an RDA.

·         Tolerable upper intake(UL)

Maximum daily intake unlikely to cause adverse health effects

Physiological role

-          TPP is necessary for the action of pyruvate and alpha-ketoglutratein carbohydrate metabolism and for action of transketolase.

-          These TTP also involved in HMP shunt and glycolysis.

-          Thiamine maintain healthy skin and muscle tone

-          Reduces risk of pancreatic cancer

-          Enhance immune and nervous system function, promote cell growth and divison , including that of red blood cells that help prevent anemia

-          Thiamine help to convert carbohydrate into glucose.

Mode of action

Activation of thiamine

Deficiency of vitamin B₁

defficiency of vitamin b₁can affect the cardiovascular, nervous and immune system as in commonly seen in wet beriberi,dry beriberiand Wernicke korsaff syndrome.

Beriberi

Beriberi is a serious and potentially lite threalling condition that develops it a person has defficiency  of thiamin . A severe in this nutrients can leads to lasting damage in nervous system and heart, two forms:

·        Wet beriberi  

       Wet briberi, which mainly affects the cardiovascular system causing poor circulation and fluid build up in the tissues.

·        Dry beriberi

        Dry beriberi which primarly affects the nervous system, leading to the deganeratians of the nerves typically begins in legs and arms.

SYMPTOM  OF BERIBERI :

·         Increased heart rate.

·         Shortness of breath .

·         Swelling in legs and feet .

·         General pain body aches .

·         Vomiting , difficulty in walking.

DIAGNOSIS OF BERIBERI :

Doctor relay on both blood and urine test to help  measure the level of thiamine in person blood stream to diagnosis beriberi.

TREATMENT OF BERIBERI :

The goal of treatment for beriberi  is to increase thiamin level in body and recomende oval supplement or injection to deliver this health.

Wernicke-karsakoff syndrome

         Wernicke karsoff is type of brain disorders caused by a lack of brain disorder caused by lack of thiamin, developed in alcoholic due to decrease absorption of B₁

SYMPTOMS OF WERNICKE :

·         Confusians.

·         Loss of muscles co-ordination.

·         Changes in visian such as mystagmus (rapid, uncontroll eye movement

SYMPTOMS OF KARSKOFF :

·         Memory loss.

·         Difficult forming new memories.

·         Hallucination.

·         Confabulation (making up stories)

CAUSES :

Because drinking hearily interferes with your body absorbed or store thiamine.

DIAGNOSIS : 

Doctor relay on both blood and urine test to help  measure the level of thiamine in person

blood stream to diagnosis beriberi.

TRATEMENT :

The goal of treatment for beriberi  is to increase thiamin level in body and recomende oval supplement or injection to deliver this health.

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