SIADH (Syndrome of Inappropriate ADH secretion) - mechanism, pathophysiology, treatment

hello in this video we're gonna talk about syndrome of inappropriate antidiuretic hormone secretion also known as SIADH the hypothalamus is a region of the brain involved in coordinating the physiologic responses of different organs that together maintain homeostasis the hypothalamus have neurons running towards the posterior pituitary which produces neuropeptides and will release them into circulation ADH also known as arginine vasopressin is one of the neuro peptides which are released into circulation an increase in serum osmolarity or a decrease in blood volume will stimulate the hypothalamus to produce antidiuretic hormone also known as ADH ADH is produced by magnocellular neurons which will carry and then release them from the posterior pituitary gland into systemic circulation so what does ATH do well ADH main effect is to increase water re-absorption from the kidney how do they do this the kidneys are made up of their functional units called nephrons and here is one nephron as an example afferent arteriole will bring blood to the head of the nephron forming what's known as the glomerulus the glomerulus will filter blood through and into the nephron tubules it enters the first part of the nephron called the proximal convoluted tubule the proximal convoluted tubule have channels on it called aquaporin one channels which reabsorb water the aquaporin one channels are responsible for reabsorbing 90% of water that is filtered through the nephron the filtrate in the tube you'll remain that will continue along the tube you'll through the loop of Henle the distal convoluted duct the remaining 10% of waters actually reabsorbed in the colon conduct and the distal convoluted tubule and is primarily driven by the hormone ADH ADH increases expression of aquaporin two channels which results in water re-absorption despite being responsible for only 10% of water absorption from the nephron this goes a long way let's take a closer look at how ADH actually reabsorbs water there are cells which line the collecting ducts called principal cells principal cells have all these aquaporin type 2 channels in this this endo zone the site ozone ready to be expressed by the cell membrane ADH will travel by blood and travel to the nephron ADH will bind onto ATH receptors on the basal surface so the bottom part of the principal cells and this will stimulate then the expression of aquaporin type 2 channels on the apical surface of the principal cells these channels will increase the reabsorption of water from the nephron sugar water enters the cell the water then gets reabsorbed into circulation the increase in water reabsorption increases blood volume and also decreased serum osmolarity SIADH is syndrome of inappropriate secretion of adh resulting in a lot of ADH in the blood in the serum and also increases the ADH activity causes of syndrome of inappropriate antidiuretic hormone secretion include trauma to the brain or the pituitary area central nervous system disorders or infections such as meningitis as well as ectopic ADH production such as from lung cancer or even non neoplastic ADH such as from respiratory infections regardless of the cause the pathophysiology of SIADH begins with uncontrolled secretion of adh when this happens you retain more water you increase blood volume and you will decrease serum osmolarity hypo osmolarity or hypo osmolality is usually a result of dye dilution and secretion of sodium from the body what contributes to water retention is also if you drink more in response to a decrease in blood volume or an increase in serum osmolarity now the syndrome of inappropriate antidiuretic hormone secretion you know continues and you get an increase in blood volume for a while and after a while you will actually cause stretching of the hot muscle walls in the atrium and in the ventricles and when this happens the hot produces naturally peptides are a and P and B and P as a response now a and P and BMP inhibits renin release and activity through a few mechanisms regardless the end result is a decrease in activity of the renin-angiotensin-aldosterone system and because of this you decrease angiotensin ii function and also aldosterone function a reduction in aldosterone and an increase in a and p and v MP the naturally peptides will promote natural rhesus natural rhesus is the excretion of sodium in the urine natural reefs is results in a decrease in blood volume and also a decrease in serum osmolarity a decrease in blood volume means it will stimulate ADH release and promote its activity again which is already present in SIADH with so much SIADH remember there will be an increase in blood volume which really means that you are increasing the GFR the amount of blood going into the kidneys and as a response this will also cause a decrease in renin production decrease in renin means you have decrease in the renin-angiotensin-aldosterone system which means that you will essentially promote Natura sees the excretion of sodium from the body and with that water will follow when you measure urine in people with SIADH there will be high amounts of sodium in urine the urine tends to be concentrated and when you measure someone's blood there will be low levels of sodium termed hyponatremia this cycle continues with more blood volume and decrease in serum osmolarity over time through an unknown mechanisms the kidneys will eventually adapt when the kidneys begin adapting they will try to do something interesting the number of aquaporin channels decrease at the apical surface of principle cells in order essentially to negate the increase amounts of ADH present this means that the kidneys will learn not to reabsorb water and so you will have diuresis and at sharise's peeing out water as well as sodium and this will occur even if you consume salt and even if you ingest water the urine in SIADH does not necessarily have to be concentrated and this is one of the reasons why in patients with s ADH the new steady state is a euvolemic state not fluid overloaded but also not dehydrated thanks to the mechanism we discussed just before remember si ADH is characterized by hyponatremia an increase in urine sodium excretion and euvolemic also remember clinically patients with s ADH are euvolemic despite retaining water the reason being the body learns to excrete water eventually maintaining this youthful emic state the important clinical symptoms and signs of SIADH are related to the low sodium levels in the blood now low sodium levels can be acute or chronic acute is defined by hyponatremia occurring less than 48 hours severe hyponatremia is defined as serum sodium of about 120 millimoles per liter or less and this is usually when the symptoms of hyponatremia come up acute hyponatremia is dangerous because it can cause cerebral edema neurogenic pulmonary edema seizures and even coma the mechanism of edema in acute hyponatremia can be explained here let's look at cerebral edema the dangerous complication of acute hyponatremia you can imagine here is the brain and it's neuron and here is the circulation in the circulation you have water and low sodium levels in the brain you have adequate levels including sodium and potassium now if you have suddenly low sodium in circulation according to the osmotic gradient principle water will move to the area with more solutes and so will develop a demon rapidly in chronic hyponatremia you don't get cerebral edema because of cerebral adaptation this is where because of time electrolytes from the brain are able to distribute equalizing the electrolytes in circulation and in the brain and so sodium and potassium for example can move into circulation and this allows water to equalize more safely chronic hyponatremia is characterized by nonspecific signs and symptoms such as headache nausea vomiting and seizures the other signs and symptoms of SIADH will depend on the cause of the SIADH causes of SIADH include trauma surgery CNS infections and stroke which affect the hypothalamic pituitary axis increasing the production of ADH medications also somehow increase production or the effect of ADH these medications can be remembered with the acronym car dish chemotherapy antidepressants recreational drugs diuretics inhibitors such as ACE inhibitors and SSRIs sulfonylurea and H is for hormones such as desmopressin another cause for SIADH are the malignancies which cause ectopic production of ADH common examples include small cell carcinoma of the lung and pancreatic cancer pulmonary disease such as pneumonia can increase ADH production somehow and there are nephrogenic causes mainly the mutation in the aquaporin type two channels in the distal collecting ducts which will increase the retention of water nephrogenic SIADH is aquaporin to mutation which causes aquaporin - to remain open resulting in water retention diagnosing SIADH requires a set criteria and ruling out other causes of hyponatremia so let's look at some criteria to diagnose SIADH one you need to have hyponatremia with a normal extracellular fluid state so a euvolemic state - urine osmolality needs to be higher than plasma osmolality the urine sodium needs to be greater than 20 million miles per liter and you need to relate other causes of hyponatremia this includes making sure the patient is not on diuretics here patients have to have normal function of kidneys thyroid and adrenal glands namely the production of cortisol management of SIADH is relatively similar first treat symptomatic attitude hyponatremia quickly as this can be life-threatening treat chronic hyponatremia slowly the reason for this is to prevent what's called central point in myelin OSIS which we will talk about later it's important to treat the main cause that could be leading to the low sodium and SIADH number to restrict fluid intake five hundred mils to one liter a day is good this will lead to a reduction in blood volume an increase in aldosterone and so will hopefully increase sodium retention number three administration of hypertonic saline if patients are symptomatic in any way this has to be given slowly hypertonic saline has sodium in the fluid will also increase plasma volume frizam I can also be given with patients who have features of mild fluid overload freeze amide works at the ascending loop of Henle inhibiting a try porta freezer might causes an increase in water sodium chloride and potassium excretion it's important to consider to replace the potassium chloride that's being excreted and you can give potassium chloride in the hypertonic saline solution finally the necklace cyclin can be given the mek'leth cyclin is mainly used in chronic hyponatremia the macro cycling inhibits the real action of antidiuretic hormone by any inhibiting it's binding onto the ADH receptors finally rapid correction of hyponatremia can lead to central pontine Milano sious which leads me to the complications of rapid correction of hyponatremia so imagine you are using medications fluids to increase serum sodium rapidly this means you suddenly get all this sodium in circulation remember water follows sodium so what you get is water from the brain for example escaping into circulation because of the osmotic gradient this causes shriveling and shrinkage you can say of the brain parenchyma it is termed central Ponton myelin osis because when first described it was found in the pons and what was seen was damage to the myelin sheath central pontine myelin OSIS is characterized by a progressive development of quadriplegia pseudobulbar palsy and emotional liability

Channel: Armando Hasudungan

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Keywords: SIADH, syndrome of inappropriate ADH secretion, endocrinology, SIADH pathophysiology, hyponaturaemia, medicine, SIADH lecture, approach to hyponaturaemia, hyponaturemia, Inappropriate section of vasopressin, treatment of SIADH, antidiuretic hormones, disease of SIADH, what is SIADH, SIADH mechanism

Id: qlur2m72Pmc

Length: 16min 9sec (969 seconds)

Published: Tue Oct 30 2018