Metabolic Alkalosis (ABG Interpretation - Lesson 10)

[Applause] [Music] hello this is Eric strong again and for this tenth lecture I will be talking about metabolic alkalosis the learning objectives of this lecture are to know the differential diagnosis of a metabolic alkalosis and to be able to identify the specific etiology of a metabolic alkalosis in an individual patient one way to classify the ideologies of a metabolic alkalosis is to consider what the primary issues are both which organ between the GI tract and the kidneys the problem is primarily in and what the basic mechanism is between loss of hydrogen and gain of bicarbonate for example loss of hydrogen ions in the GI tract can be due to either vomiting nasal gastric suctioning or congenital chloride diarrhea I'm going to be talking much more about the other conditions listed on this chart in a few minutes but congenital chloride diarrhea is a rare genetic defect in in epithelial anion exchanger which results in a syndrome of hyponatremia hypothermia and metabolic alkalosis usually presenting immediately after birth conditions in the kidneys which can result in loss of hydrogen include loop and thiazide diuretics mineralocorticoid excess contraction alkalosis and parter and Gittleman syndromes in the guts gain of bicarb can be due to the milk alkali syndrome or due to ingestion of sodium bicarbonate and in the kidneys contraction alkalosis can also lead to gain of bicarb I personally prefer a different scheme for classifying these ideologies based on whether the conditions are common or uncommon causes of metabolic alkalosis common ideologies include contraction alkalosis diuretics vomiting and ng suction uncommon or rare ideologies include mineralocorticoid excess hypokalemia milk alkalized syndrome ingestion of sodium bicarb barter and Gittleman syndrome and congenital chloride diarrhea I'm not suggesting here that hypokalemia is itself uncommon but rather it is an uncommon cause of a clinically relevant alkalosis in the absence of an additional process I'm going to discuss each of these ideologies one at a time including a review of the pathophysiology the reason to go into such detail is to provide you the background necessary to be able to predict which conditions can cause a metabolic alkalosis it will also help you to understand how we diagnose these ideologies and what specific therapies might exist for them one of the most common causes of a metabolic alkalosis and certainly the most common among my own patients is known as a contraction alkalosis this term refers to the metabolic alkalosis that can accompany volume depletion either actual volume depletion or the decreased effect of circulating volume that can accompany diseases such as congestive heart failure to understand the physiologic processes that drive a contraction alkalosis I'm going to go through two key diagrams to which I will will be referring again later in this lecture the first is a schematic of a nephron which might look familiar from lecture 2 in the proximal convoluted tubule we can see that bicarb and sodium reabsorption are stimulated by among other things a hormone called angiotensin 2 in the distal tubule through a complicated multi-step process another hormone called aldosterone stimulates reabsorption of sodium in exchange for secretion of both potassium and hydrogen so high levels of angiotensin 2 and aldosterone need to bicarbonate reabsorption in hydrogen secretion respectively and thus in metabolic alkalosis however what triggers high levels of angiotensin ii and aldosterone to begin with and how is it related to a patient's intravascular volume for hormonal regulation of intravascular volume as it relates to acid-base balance is a very complicated topic but I will try to simplify it as much as possible with a single slide there are several organs involved in this process most prominently of course is the kidney however there are also the adrenal glands the pituitary and hypothalamus adjacent to the base of the brain the liver and the lungs for this diagram I've colored physiologic effects in green enzymes in blue and hormones and pre hormones in tan regulation of intravascular volume starts with low blood pressure more accurately low renal perfusion low renal perfusion stimulates secretion of an enzyme called renin from the juxtaglomerular cells in the kidney juxtaglomerular cells are actually specialized smooth muscle cells within the afferent arteriole whose sole purpose is to secrete renin reading axon a pre hormone called angiotensinogen which is initially formed in the liver to create yet another pre hormone called angiotensin one angiotensin one travels in the systemic circulation to the lungs where the uncreated li named angiotensin converting enzyme transforms it into angiotensin 2 an active hormone some of angiotensin twos actions include vasoconstriction and increased thirst these actions make perfect sense if you remember that low renal perfusion was the trigger for this brief cascade of events initially separate from the Iranian angiotensin system is the hypothalamic-pituitary-adrenal system this begins in the hypothalamus with the release of a hormone called cortical tropen releasing hormone or CRH which travels locally to the anterior lobe of the pituitary gland where it triggers release of ACTH ACTH travels systemically to the adrenals where it stimulates conversion of cholesterol into a variety of steroid precursors through a sequence of biochemical steps beyond the scope of this lecture some of these precursors are converted into cortisol in the zona fasciculata of the adrenal cortex and into a last drone in the zona glomerulosa cortisol negatively inhibits the release of CRH the direct link between the iranian angiotensin system and the hypothalamic-pituitary-adrenal system is the fact that angiotensin ii in addition to its other actions stimulates production of aldosterone together angiotensin ii and aldosterone act on the kidney as we just saw on the prior slide of the nephron with angiotensin ii acting in the proximal tubule in aldosterone acting in the distal tubule and collecting duct the combined actions in the nephron includes sodium reabsorption bicarbonate reabsorption potassium secretion and hydrogen secretion in addition cortisol actually has some activity in the nephron similar to that of aldosterone which is only clinically relevant when cortisol levels are in great excess this is a good place to mention that aldosterone cortisol and any other steroid hormone which acts on the kidney in some way to promote sodium reabsorption is known as a mineralocorticoid I will talk more about the mineralocorticoids in a few minutes one of the net results of all this of course is a metabolic alkalosis in addition the sodium reabsorption promotes water reabsorption which in turn increases blood pressure and thus renal perfusion high renal perfusion is responsible for negative feedback on the duct juxtaglomerular cells and subsequent decrease treinen secretion although a complete discussion of the regulation of intravascular volume would also include things such as ADH ANP and other hormones this diagram is sufficient for an understanding of the generation of a contraction alkalosis the next most common etiology of the metabolic alkalosis is the use of diuretics here is a nephron once again with the proximal convoluted tubule loop of Henle early distal tubules and the collecting duct I'm going to add in one additional segment that thick ascending limb which I haven't previously mentioned in this course to understand the role of directs in the kidney I first must mention two important transporters which are transmembrane proteins on the luminal side of the cells lining the nephron these transporters are responsible for movement of solutes from the tube you lumen back into the intracellular space from which they will eventually make their way back into the systemic circulation the first of these transporters is in the thick sending limb where it leads to these simultaneous reabsorption of one sodium ion one potassium ion and two chloride ions the second transporter is in the early distal tubules where it leads to simultaneous reabsorption of one sodium and one chlorine ion there are two classes of diuretics that lead to metabolic alkalosis the first are called loop diuretics these include furosemide or lasix bumetanide or bumex torse amide and ethic rinic acid loop diuretics inhibit the co transporter in the thick ascending limb which prevents sodium reabsorption and lets leads to an increased excretion of water the second relevant class of diuretics is the thiazide diuretics these include hydrochlorothiazide chloro thiazide also known as dl4000 and Mottola zone the iodides act by inhibiting this co-transporter loop and thiazide diuretics can lead to a metabolic alkalosis through two mechanisms first dehydration from excessive diuresis can trigger a contraction alkalosis alternatively blockage of sodium reabsorption proximally will need to increase delivery of sodium to the collecting duct this will shift the electrochemical balance or sodium is reabsorbed in exchange for secretion of potassium and hydrogen thus diuretics can lead to this effect even if they don't trigger increased levels of aldosterone next is vomiting and nasal gastric suction these two have identical effects on a person's physiology and can lead to a metabolic alkalosis as a consequence of volume depletion and a secondary contraction alkalosis as well as direct loss of hydrogen in gastric fluids rich in hydrochloric acid the effect of vomiting and NG suction really is that straightforward the next ideology is mineralocorticoid excess and this is a bit more complicated a state of mineralocorticoid excess is suggested by the constellation of hypertension hypokalemia and a metabolic alkalosis so here is this chart again showing how hormones regulate in vascular volume most forms of mineralocorticoid excess are due to defects here in the hypothalamic-pituitary-adrenal axis however a very similar state can develop on account of excess levels of renin as well when I think about the specific ideologies of mineralocorticoid excess I think primarily of two major categories first is hyperaldosteronism in which as the name implies an elevated aldosterone level is the predominant problem the other category is Cushing syndrome where either an elevated cortisol level or the presence of an exogenous steroid is the predominant problem for those of you curious about medical history Cushing's syndrome is named not after an endocrinologist that's most assumed but rather an American named Harvey Cushing was actually a neurosurgeon and who had described this syndrome the context of a malfunctioning pituitary gland Cushing led quite an interesting life among which was attending to the mortally wounded son of one of his heroes William Osler in a flemish battlefield during World War one getting back to metabolic alkalosis a hyperaldosteronism can in turn be broken down into two subcategories the first is when elevated aldosterone levels occur on their own in the absence of another triggering hormone abnormality this is termed primary hyperaldosteronism primary hyperaldosteronism is usually caused either by bilateral adrenal hyperplasia or an adrenal adenoma secreting aldosterone this latter condition is called con syndrome after Jerome Kahn and American endocrinologist from the University of Michigan other more rare causes of primary hyperaldosteronism include Anna dosterone secreting adrenal carcinoma a rare genetic disorder called glucocorticoid remedial aldosterone ism in which exogenously codes such as prednisone will part actually correct hypertension and finally a number of rare forms of congenital adrenal hyperplasia the details of which are fascinating to pediatric endocrinologist but which are well beyond the scope of this talk in addition to primary hyperaldosteronism a nearly identical syndrome can be caused by an inappropriately elevated level of renin a condition known as secondary hyperaldosteronism hi greening results in hi auntie intention to which in turn stimulates excess production of aldosterone hi reading levels are usually due to stenosis of one or both of the adrenal arteries by either atherosclerosis or fibromuscular dysplasia fibromuscular dysplasia is an uncommon but probably under recognized cause of refractory hypertension presenting under the age of 40 with a slight female predominance lenience secreting tumors of the juxtaglomerular apparatus have also been described but are quite rare moving on to Cushing's syndrome this can be caused at any step along the hypothalamic-pituitary-adrenal axis so the first cause is an elevated level of CRH caused by a CRH producing tumor which for some reason is best described in bronchial carcinoid tumors which are quite rare the next step along the axis is an elevated ACTH when caused by the ACTH secreting pituitary adenoma it's called Cushing's disease elevator ACTH can also be caused by ectopic production by a tumor usually small cell lung cancer next in elevated cortisol can be the result of an adrenal adenoma a cortisol secreting adrenal carcinoma or from chronic licorice ingestion licorice contains glycine retinic acid a natural steroid that inhibits an enzyme normally responsible converting cortisol into cortisone which has much less mineralocorticoid activity a synthetic form of life Cerreta neck acid known as carbon oxalá is occasionally used in the UK for various esophageal disorders and has hyperaldosteronism as a side-effect the final cause of cushing's syndrome is exogenous steroids usually prednisone one final miscellaneous cause of apparent mineralocorticoid excess is little syndrome which is a rare autosomal dominant disorder in which there is excess sodium reabsorption and potassium secretion in the collecting duct hypokalemia is the next general etiology of a metabolic alkalosis hypokalemia leads to a metabolic alkalosis through several mechanisms first in the presence of hypokalemia there is a shift of potassium ions from the intracellular space to the extracellular space in exchange for shift of hydrogen from the extracellular space to the intracellular space in addition within the nephron hypokalemia is a stimulus for the reabsorption of bicarbonate in the proximal tubule and for secretion of hydrogen in the collecting duct milk alkali syndrome this syndrome consists of the constellation of hypercalcemia metabolic alkalosis and renal insufficiency it is associated with the ingestion of a large amount of calcium and absorbable alkali it was originally described in patients consuming larger quantities of milk and sodium bicarbonate for treatment of peptic ulcer disease but currently is more common in older women taking calcium supplements for prevention of osteoporosis milk alkali syndrome can also be seen Oceania and the Far East where consumption of baitul nuts is sometimes accompanied with either calcium carbonate or calcium hydroxide although the mechanism of pathogenesis superficially seems obvious various attempts to explain the complete pathophysiology of milk alkali syndrome have not been fully convincing and a definitive description of the disease remains elusive martyr and Gittleman syndromes are autosomal recessive disorders of the membrane transporters in the nephron their shared features include a metabolic alkalosis hypokalemia high reading and aldosterone levels and a lack of hypertension distinguishing features between the two include the following patients with Bartter syndrome frequently have mental and growth retardation and hyper calcia it usually presents in young childhood and is exceptionally rare patients with Gittleman syndrome have a predominant complained of muscle cramps and are hypocalcemic Gittleman syndrome presents in adolescents and is very rare but not as much so as barter to understand exactly how these syndromes work here is a picture of the nephron again with our tubular transport proteins drawn in you will recall that the target of loop diuretics is a so um potassium chloride transporter in the thick ascending limb in Bartter syndrome this is the effective protein therefore Bartter syndrome biochemically mimics treatment with Luke diuretics the thiazide diuretics block the sodium chloride transporter in the early distal tubule and this is where the problem is with Gittleman syndrome which therefore mimics treatment with a thiazide the last topic I would like to address in this lecture is how to approach a metabolic alkalosis and establish a diagnosis the first step is to assess volume status if it is low the history will almost always be sufficient to explain the situation as the patient will have either an obvious contraction alkalosis from primary dehydration diuretics vomiting or ng suction if none of those are parents and the patient is in the appropriate age demographic you may be dealing with one of those rare cases of barter or Gittleman syndromes on the other hand if the volume status is either normal or high the next step is to assess the blood pressure and serum potassium level if blood pressure is normal and potassium is low then hypokalemia is in itself the likely cause of the alkalosis of course hypokalemia has its own differential diagnosis which I won't get into here if the blood pressure and potassium are both normal then I would consider either the administration of exogenous alkaline such as sodium bicarbonate tablets or milk alkali syndrome finally if the patient has significant hypertension then the condition to worry about is mineralocorticoid excess at that point meaning and aldosterone levels should be checked the appropriate means of measurement and interpretation of reading in aldosterone is a complicated topic that I won't have time to get into in any detail in this lecture but the basic interpretation can be deduced from the aforementioned discussion of the body's hormonal regulation of intravascular volume therefore a high aldosterone and low renin level suggest primary hyperaldosteronism a haya dosterone and a high reading suggest secondary hyperaldosteronism a relatively normal aldosterone and normal reading suggest Cushing's syndrome and finally low aldosterone and low reading suggest an extra hormonal cause of the apparent mineralocorticoid access such as exogenous steroids licorice ingestion and the rare little syndrome that does it for the differential diagnosis of a metabolic alkalosis the next two lectures will cover primary respiratory disorders [Music] you

Channel: Strong Medicine

Views: 71,221

Keywords: metabolic alkalosis, contraction alkalosis, mineralocorticoid, cushing's syndrome, cushing's disease, conn's syndrome, hyperaldosteronism, renin, angiotensin, juxtaglomerular, hypokalemia, diuretic, lasix, arterial blood gas, abg, stanford, medical lecture, eric strong, metabolic alkaloses, differential diagnosis

Id: ni-J1bll8m4

Length: 20min 38sec (1238 seconds)

Published: Mon Apr 30 2012