Gitelman Syndrome

Overview

Definition

Gitelman syndrome (GS) is a rare genetic autosomal recessive Autosomal recessive Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal recessive diseases are only expressed when 2 copies of the recessive allele are inherited. Autosomal Recessive and Autosomal Dominant Inheritance disorder that affects the thiazide-sensitive Na⁺–Cl^– cotransporter (NCC) in the distal convoluted tubule (DCT), leading to a salt-wasting tubulopathy. 

Epidemiology

• Prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency:
  • 1–10 per 40,000 individuals
  • Heterozygous carriers Carriers The Cell: Cell Membrane: approximately 1% of the Caucasian population
  • More common than Bartter syndrome Bartter syndrome Bartter syndrome is a rare autosomal recessive disorder that affects the kidneys and presents either antenatally with severe or life-threatening manifestations or in childhood or adulthood with a milder course, depending on the genetic defect. Clinical disease results from defective renal reabsorption of sodium chloride in the thick ascending limb of the loop of Henle. Bartter Syndrome
• No sex Sex The totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism. Gender Dysphoria predisposition

Etiology

• Autosomal recessive inheritance Autosomal recessive inheritance Autosomal Recessive and Autosomal Dominant Inheritance: For a person to be affected, a mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations must be present on both genes Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. DNA Types and Structure encoding the NCC. 
• Carrier Carrier Vaccination: A person with only 1 mutated gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics remains unaffected.
• When 2 unaffected carriers Carriers The Cell: Cell Membrane have children, there is: 
  • A 25% chance of the offspring being affected
  • A 50% chance of the offspring being an unaffected carrier Carrier Vaccination
  • A 25% chance of the offspring being unaffected and not a carrier Carrier Vaccination
• The mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations is present in the SLC12A3 gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics (80% of individuals) and, rarely, in the CLCNKB gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics.

Pathophysiology

Normal physiology in the DCT

The DCT is the smallest portion of the duct system in a nephron Nephron The functional units of the kidney, consisting of the glomerulus and the attached tubule. Kidneys: Anatomy. It measures about 5 mm MM Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma in size and starts from the macula Macula An oval area in the retina, 3 to 5 mm in diameter, usually located temporal to the posterior pole of the eye and slightly below the level of the optic disk. It is characterized by the presence of a yellow pigment diffusely permeating the inner layers, contains the fovea centralis in its center, and provides the best phototropic visual acuity. It is devoid of retinal blood vessels, except in its periphery, and receives nourishment from the choriocapillaris of the choroid. Eye: Anatomy densa. Characteristics of the DCT are as follows:

• Lined with simple cuboidal epithelium Simple cuboidal epithelium Surface Epithelium: Histology without microvilli
• Presence of a large number of mitochondria Mitochondria Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive ribosomes, transfer RNAs; amino Acyl tRNA synthetases; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs. Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. The Cell: Organelles and Na⁺/K⁺-ATPase pumps in the basolateral membrane
• Impermeable to water and urea Urea A compound formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. Urea Cycle
• Contains the NCC, which is the target of thiazide Thiazide Heterocyclic compounds with sulfur and nitrogen in the ring. This term commonly refers to the benzothiadiazines that inhibit sodium-potassium-chloride symporters and are used as diuretics. Hyponatremia diuretics Diuretics Agents that promote the excretion of urine through their effects on kidney function. Heart Failure and Angina Medication
• Functions of the DCT:
  • Regulation of pH pH The quantitative measurement of the acidity or basicity of a solution. Acid-Base Balance by secretion Secretion Coagulation Studies of H⁺ ions and reabsorption of HCO₃^–, or vice versa
  • Reabsorption of Na⁺, Cl^–, Mg²⁺, and calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes ( Ca CA Condylomata acuminata are a clinical manifestation of genital HPV infection. Condylomata acuminata are described as raised, pearly, flesh-colored, papular, cauliflower-like lesions seen in the anogenital region that may cause itching, pain, or bleeding. Condylomata Acuminata (Genital Warts)²⁺)
  • Secretion Secretion Coagulation Studies of K⁺

Pathophysiology

Gitelman syndrome leads to the loss of function Loss of Function Inflammation of the NCC → electrolyte abnormalities due to interference with the normal functioning of the DCT

• Gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics mutations inactivate the NCC:
  • Normally functions to reabsorb Na⁺ and Cl^– from the DCT
  • Inactivation prevents reabsorption → ↑ Na⁺ and Cl^– delivery to the collecting duct Collecting duct Straight tubes commencing in the radiate part of the kidney cortex where they receive the curved ends of the distal convoluted tubules. In the medulla the collecting tubules of each pyramid converge to join a central tube (duct of bellini) which opens on the summit of the papilla. Renal Cell Carcinoma
• Impaired salt reabsorption → ↑ water loss
• Volume contraction → activation of RAAS RAAS A blood pressure regulating system of interacting components that include renin; angiotensinogen; angiotensin converting enzyme; angiotensin i; angiotensin ii; and angiotensinase. Renin, an enzyme produced in the kidney, acts on angiotensinogen, an alpha-2 globulin produced by the liver, forming angiotensin I. Angiotensin-converting enzyme, contained in the lung, acts on angiotensin I in the plasma converting it to angiotensin II, an extremely powerful vasoconstrictor. Angiotensin II causes contraction of the arteriolar and renal vascular smooth muscle, leading to retention of salt and water in the kidney and increased arterial blood pressure. In addition, angiotensin II stimulates the release of aldosterone from the adrenal cortex, which in turn also increases salt and water retention in the kidney. Angiotensin-converting enzyme also breaks down bradykinin, a powerful vasodilator and component of the kallikrein-kinin system. Adrenal Hormones
• ↑ Renin Renin A highly specific (leu-leu) endopeptidase that generates angiotensin I from its precursor angiotensinogen, leading to a cascade of reactions which elevate blood pressure and increase sodium retention by the kidney in the renin-angiotensin system. Renal Sodium and Water Regulation and aldosterone Aldosterone A hormone secreted by the adrenal cortex that regulates electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium. Hyperkalemia activity in the collecting duct Collecting duct Straight tubes commencing in the radiate part of the kidney cortex where they receive the curved ends of the distal convoluted tubules. In the medulla the collecting tubules of each pyramid converge to join a central tube (duct of bellini) which opens on the summit of the papilla. Renal Cell Carcinoma results in:
  • ↑ K⁺ excretion → hypokalemia Hypokalemia Hypokalemia is defined as plasma potassium (K+) concentration < 3.5 mEq/L. Homeostatic mechanisms maintain plasma concentration between 3.5-5.2 mEq/L despite marked variation in dietary intake. Hypokalemia can be due to renal losses, GI losses, transcellular shifts, or poor dietary intake. Hypokalemia
  • ↑ H⁺ excretion → metabolic alkalosis Alkalosis A pathological condition that removes acid or adds base to the body fluids. Respiratory Alkalosis
• Additionally, there may be:
  • ↓ Mg²⁺ reabsorption → renal Mg²⁺ wasting → hypomagnesemia Hypomagnesemia A nutritional condition produced by a deficiency of magnesium in the diet, characterized by anorexia, nausea, vomiting, lethargy, and weakness. Symptoms are paresthesias, muscle cramps, irritability, decreased attention span, and mental confusion, possibly requiring months to appear. Deficiency of body magnesium can exist even when serum values are normal. In addition, magnesium deficiency may be organ-selective, since certain tissues become deficient before others. Electrolytes
  • ↓ Urinary calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes excretion

Clinical Presentation

Individuals with GS have mild-to-moderate symptoms without limitation in daily activity. These individuals present after the 1st decade of life in adolescence or early adulthood (rarely in infancy).

The classic clinical presentation is the triad of: 

• Hypokalemia Hypokalemia Hypokalemia is defined as plasma potassium (K+) concentration < 3.5 mEq/L. Homeostatic mechanisms maintain plasma concentration between 3.5-5.2 mEq/L despite marked variation in dietary intake. Hypokalemia can be due to renal losses, GI losses, transcellular shifts, or poor dietary intake. Hypokalemia
• Metabolic alkalosis Alkalosis A pathological condition that removes acid or adds base to the body fluids. Respiratory Alkalosis 
• Normal or low blood pressure

Other signs and symptoms include:

• Manifestations of hypokalemia Hypokalemia Hypokalemia is defined as plasma potassium (K+) concentration < 3.5 mEq/L. Homeostatic mechanisms maintain plasma concentration between 3.5-5.2 mEq/L despite marked variation in dietary intake. Hypokalemia can be due to renal losses, GI losses, transcellular shifts, or poor dietary intake. Hypokalemia:
  • Muscle twitching, cramps Cramps Ion Channel Myopathy, and weakness
  • Constipation Constipation Constipation is common and may be due to a variety of causes. Constipation is generally defined as bowel movement frequency < 3 times per week. Patients who are constipated often strain to pass hard stools. The condition is classified as primary (also known as idiopathic or functional constipation) or secondary, and as acute or chronic. Constipation
  • Severe fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia
  • Polyuria Polyuria Urination of a large volume of urine with an increase in urinary frequency, commonly seen in diabetes. Renal Potassium Regulation or nocturia Nocturia Frequent urination at night that interrupts sleep. It is often associated with outflow obstruction, diabetes mellitus, or bladder inflammation (cystitis). Diabetes Insipidus
  • Cardiac arrhythmias and cardiac arrest Cardiac arrest Cardiac arrest is the sudden, complete cessation of cardiac output with hemodynamic collapse. Patients present as pulseless, unresponsive, and apneic. Rhythms associated with cardiac arrest are ventricular fibrillation/tachycardia, asystole, or pulseless electrical activity. Cardiac Arrest (in severe cases)
• Manifestations of hypomagnesemia Hypomagnesemia A nutritional condition produced by a deficiency of magnesium in the diet, characterized by anorexia, nausea, vomiting, lethargy, and weakness. Symptoms are paresthesias, muscle cramps, irritability, decreased attention span, and mental confusion, possibly requiring months to appear. Deficiency of body magnesium can exist even when serum values are normal. In addition, magnesium deficiency may be organ-selective, since certain tissues become deficient before others. Electrolytes:
  • Paresthesias Paresthesias Subjective cutaneous sensations (e.g., cold, warmth, tingling, pressure, etc.) that are experienced spontaneously in the absence of stimulation. Posterior Cord Syndrome, especially in the face
  • Muscle cramps Cramps Ion Channel Myopathy
  • Tetany Tetany A disorder characterized by muscle twitches, cramps, and carpopedal spasm, and when severe, laryngospasm and seizures. This condition is associated with unstable depolarization of axonal membranes, primarily in the peripheral nervous system. Tetany usually results from hypocalcemia or reduced serum levels of magnesium that may be associated with hyperventilation; hypoparathyroidism; rickets; uremia; or other conditions. Hypocalcemia
  • Arthralgias
  • Myalgias Myalgias Painful sensation in the muscles. Tick-borne Encephalitis Virus
• Salt cravings
• Thirst
• Chondrocalcinosis in adulthood: associated with inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation of joints
• Seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures in severe cases
• Growth delay is seen in individuals affected at a young age.

Diagnosis

A detailed evaluation of GS is necessary when an individual presents with unexplained hypokalemia Hypokalemia Hypokalemia is defined as plasma potassium (K+) concentration < 3.5 mEq/L. Homeostatic mechanisms maintain plasma concentration between 3.5-5.2 mEq/L despite marked variation in dietary intake. Hypokalemia can be due to renal losses, GI losses, transcellular shifts, or poor dietary intake. Hypokalemia, metabolic alkalosis Alkalosis A pathological condition that removes acid or adds base to the body fluids. Respiratory Alkalosis, and normal or low blood pressure. Because of its rare occurrence compared with other renal disorders with similar symptoms, other causes should be ruled out.

Lab tests

• Serum electrolyte levels:
  • ↓ K⁺
  • ↓ or normal Mg²⁺
  • ↑ bicarbonate Bicarbonate Inorganic salts that contain the -HCO3 radical. They are an important factor in determining the ph of the blood and the concentration of bicarbonate ions is regulated by the kidney. Levels in the blood are an index of the alkali reserve or buffering capacity. Electrolytes
• ↑ Renin Renin A highly specific (leu-leu) endopeptidase that generates angiotensin I from its precursor angiotensinogen, leading to a cascade of reactions which elevate blood pressure and increase sodium retention by the kidney in the renin-angiotensin system. Renal Sodium and Water Regulation
• ↑ Aldosterone Aldosterone A hormone secreted by the adrenal cortex that regulates electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium. Hyperkalemia
• ↑ Blood pH pH The quantitative measurement of the acidity or basicity of a solution. Acid-Base Balance ( alkalosis Alkalosis A pathological condition that removes acid or adds base to the body fluids. Respiratory Alkalosis)
• Urinary tests:
  • Na⁺: ↑ excretion
  • K⁺: ↑ excretion
  • Cl^–: ↑ excretion
  • Mg²⁺: ↑ excretion
  • Ca CA Condylomata acuminata are a clinical manifestation of genital HPV infection. Condylomata acuminata are described as raised, pearly, flesh-colored, papular, cauliflower-like lesions seen in the anogenital region that may cause itching, pain, or bleeding. Condylomata Acuminata (Genital Warts)²⁺: ↓ excretion

Genetic testing Genetic Testing Detection of a mutation; genotype; karyotype; or specific alleles associated with genetic traits, heritable diseases, or predisposition to a disease, or that may lead to the disease in descendants. It includes prenatal genetic testing. Myotonic Dystrophies

Genetic testing Genetic Testing Detection of a mutation; genotype; karyotype; or specific alleles associated with genetic traits, heritable diseases, or predisposition to a disease, or that may lead to the disease in descendants. It includes prenatal genetic testing. Myotonic Dystrophies is highly specific and sensitive, and a majority of affected individuals show mutations in 2 particular genes Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. DNA Types and Structure:

• SLC12A3 (80% of affected individuals)
• CLCNKB

Management and Prognosis

Management

The goals of management are to minimize the effects of extracellular volume depletion Volume depletion Volume status is a balance between water and solutes, the majority of which is Na. Volume depletion refers to a loss of both water and Na, whereas dehydration refers only to a loss of water. Volume depletion can be caused by GI losses, renal losses, bleeding, poor oral Na intake, or third spacing of fluids. Volume Depletion and Dehydration and correct electrolyte deficiencies.

• Asymptomatic individuals:
  • Need regular Regular Insulin physician evaluation for electrolyte imbalances
  • Lab tests for electrolytes Electrolytes Electrolytes are mineral salts that dissolve in water and dissociate into charged particles called ions, which can be either be positively (cations) or negatively (anions) charged. Electrolytes are distributed in the extracellular and intracellular compartments in different concentrations. Electrolytes are essential for various basic life-sustaining functions. Electrolytes every 6–12 months
• Hypomagnesemia Hypomagnesemia A nutritional condition produced by a deficiency of magnesium in the diet, characterized by anorexia, nausea, vomiting, lethargy, and weakness. Symptoms are paresthesias, muscle cramps, irritability, decreased attention span, and mental confusion, possibly requiring months to appear. Deficiency of body magnesium can exist even when serum values are normal. In addition, magnesium deficiency may be organ-selective, since certain tissues become deficient before others. Electrolytes:
  • Lifelong supplementation with oral magnesium Magnesium A metallic element that has the atomic symbol mg, atomic number 12, and atomic weight 24. 31. It is important for the activity of many enzymes, especially those involved in oxidative phosphorylation. Electrolytes chloride Chloride Inorganic compounds derived from hydrochloric acid that contain the Cl- ion. Electrolytes in 3–4 divided doses/day
  • Regular Regular Insulin monitoring of serum levels
  • Tetany Tetany A disorder characterized by muscle twitches, cramps, and carpopedal spasm, and when severe, laryngospasm and seizures. This condition is associated with unstable depolarization of axonal membranes, primarily in the peripheral nervous system. Tetany usually results from hypocalcemia or reduced serum levels of magnesium that may be associated with hyperventilation; hypoparathyroidism; rickets; uremia; or other conditions. Hypocalcemia requires IV magnesium Magnesium A metallic element that has the atomic symbol mg, atomic number 12, and atomic weight 24. 31. It is important for the activity of many enzymes, especially those involved in oxidative phosphorylation. Electrolytes chloride Chloride Inorganic compounds derived from hydrochloric acid that contain the Cl- ion. Electrolytes.
• Hypokalemia Hypokalemia Hypokalemia is defined as plasma potassium (K+) concentration < 3.5 mEq/L. Homeostatic mechanisms maintain plasma concentration between 3.5-5.2 mEq/L despite marked variation in dietary intake. Hypokalemia can be due to renal losses, GI losses, transcellular shifts, or poor dietary intake. Hypokalemia:
  • K⁺ levels should be monitored to avoid cardiac arrhythmias.
  • Potassium chloride Potassium chloride A white crystal or crystalline powder used in buffers; fertilizers; and explosives. It can be used to replenish electrolytes and restore water-electrolyte balance in treating hypokalemia. Esophagitis supplementation will likely be needed.
  • Potassium-sparing diuretic:
    • Amiloride Amiloride A pyrazine compound inhibiting sodium reabsorption through sodium channels in renal epithelial cells. This inhibition creates a negative potential in the luminal membranes of principal cells, located in the distal convoluted tubule and collecting duct. Negative potential reduces secretion of potassium and hydrogen ions. Amiloride is used in conjunction with diuretics to spare potassium loss. Liddle Syndrome
    • With aldosterone Aldosterone A hormone secreted by the adrenal cortex that regulates electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium. Hyperkalemia antagonist activity: spironolactone Spironolactone A potassium sparing diuretic that acts by antagonism of aldosterone in the distal renal tubules. It is used mainly in the treatment of refractory edema in patients with congestive heart failure, nephrotic syndrome, or hepatic cirrhosis. Its effects on the endocrine system are utilized in the treatments of hirsutism and acne but they can lead to adverse effects. Potassium-sparing Diuretics and eplerenone Eplerenone A spironolactone derivative and selective aldosterone receptor antagonist that is used in the management of hypertension and congestive heart failure, post-myocardial infarction. Potassium-sparing Diuretics
    • Affected individuals should be carefully monitored to avoid hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension.
  • ARBs ARBs Agents that antagonize angiotensin receptors. Many drugs in this class specifically target the angiotensin type 1 receptor. Heart Failure and Angina Medication or ACEis ACEIs A class of drugs whose main indications are the treatment of hypertension and heart failure. They exert their hemodynamic effect mainly by inhibiting the renin-angiotensin system. They also modulate sympathetic nervous system activity and increase prostaglandin synthesis. They cause mainly vasodilation and mild natriuresis without affecting heart rate and contractility. Heart Failure and Angina Medication may also be used.
• Sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia loss:
  • Salt intake is encouraged.
  • Sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia chloride Chloride Inorganic compounds derived from hydrochloric acid that contain the Cl- ion. Electrolytes supplementation may be needed.
• Kidney transplantation Kidney Transplantation The transference of a kidney from one human or animal to another. Organ Transplantation:
  • Rare, for individuals with end-stage renal disease
  • Tubular abnormalities resolve without recurrence after kidney transplantation Kidney Transplantation The transference of a kidney from one human or animal to another. Organ Transplantation.

Prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas

• Generally good
• The ability to perform daily life activities varies among affected individuals.
• Progression to renal insufficiency is extremely rare.
• GS does not affect life expectancy Life expectancy Based on known statistical data, the number of years which any person of a given age may reasonably expected to live. Population Pyramids.

Differential Diagnosis

• Bartter syndrome Bartter syndrome Bartter syndrome is a rare autosomal recessive disorder that affects the kidneys and presents either antenatally with severe or life-threatening manifestations or in childhood or adulthood with a milder course, depending on the genetic defect. Clinical disease results from defective renal reabsorption of sodium chloride in the thick ascending limb of the loop of Henle. Bartter Syndrome: a rare genetic disorder that results in impaired NaCl reabsorption in the thick ascending limb Thick ascending limb Renal Sodium and Water Regulation of the loop of Henle Loop of Henle The U-shaped portion of the renal tubule in the kidney medulla, consisting of a descending limb and an ascending limb. It is situated between the proximal kidney tubule and the distal kidney tubule. Tubular System. Bartter syndrome Bartter syndrome Bartter syndrome is a rare autosomal recessive disorder that affects the kidneys and presents either antenatally with severe or life-threatening manifestations or in childhood or adulthood with a milder course, depending on the genetic defect. Clinical disease results from defective renal reabsorption of sodium chloride in the thick ascending limb of the loop of Henle. Bartter Syndrome presents with hypokalemia Hypokalemia Hypokalemia is defined as plasma potassium (K+) concentration < 3.5 mEq/L. Homeostatic mechanisms maintain plasma concentration between 3.5-5.2 mEq/L despite marked variation in dietary intake. Hypokalemia can be due to renal losses, GI losses, transcellular shifts, or poor dietary intake. Hypokalemia, metabolic alkalosis Alkalosis A pathological condition that removes acid or adds base to the body fluids. Respiratory Alkalosis, and delayed growth/development, and elevated urine calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes levels. Diagnosis is by blood and urine testing. Management focuses on treating symptoms and replenishing electrolytes Electrolytes Electrolytes are mineral salts that dissolve in water and dissociate into charged particles called ions, which can be either be positively (cations) or negatively (anions) charged. Electrolytes are distributed in the extracellular and intracellular compartments in different concentrations. Electrolytes are essential for various basic life-sustaining functions. Electrolytes.
• Laxative Laxative Agents that produce a soft formed stool, and relax and loosen the bowels, typically used over a protracted period, to relieve constipation. Hypokalemia abuse: seen in individuals with eating disorders for weight loss Weight loss Decrease in existing body weight. Bariatric Surgery. The 2 main disorders are bulimia Bulimia Eating an excess amount of food in a short period of time, as seen in the disorder of bulimia nervosa. It is caused by an abnormal craving for food, or insatiable hunger also known as ‘ox hunger’. Bulimia Nervosa and anorexia Anorexia The lack or loss of appetite accompanied by an aversion to food and the inability to eat. It is the defining characteristic of the disorder anorexia nervosa. Anorexia Nervosa nervosa. The associated risks are dehydration Dehydration The condition that results from excessive loss of water from a living organism. Volume Depletion and Dehydration, electrolyte abnormalities, constipation Constipation Constipation is common and may be due to a variety of causes. Constipation is generally defined as bowel movement frequency < 3 times per week. Patients who are constipated often strain to pass hard stools. The condition is classified as primary (also known as idiopathic or functional constipation) or secondary, and as acute or chronic. Constipation, infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease, and rectal prolapse Rectal prolapse Rectal prolapse, also known as rectal procidentia, is the protrusion of rectal tissue through the anus. The tissue may include just the mucosa or the full thickness of the rectal wall. Common risk factors include chronic straining, constipation, bowel motility disorders, and weakening of the pelvic floor muscles. Rectal Prolapse. It is important to treat the underlying condition and start CBT.
• Diuretic abuse: another disorder wherein people attempt to lose weight. Affected individuals take excess diuretics Diuretics Agents that promote the excretion of urine through their effects on kidney function. Heart Failure and Angina Medication to feel lighter, which leads to dehydration Dehydration The condition that results from excessive loss of water from a living organism. Volume Depletion and Dehydration and electrolyte abnormalities. Diuretic abuse is approached with CBT and educating the individual about the complications of diuretic use.
• Mineralocorticoid excess Mineralocorticoid excess A hereditary disease characterized by childhood onset hypertension, hypokalemic alkalosis, and low renin and aldosterone secretion. It results from a defect in the activity of the 11-beta-hydroxysteroid dehydrogenase type 2 enzyme which results in inadequate conversion of cortisol to cortisone. The build up of unprocessed cortisol to levels that stimulate mineralocorticoid receptors creates the appearance of having excessive mineralocorticoids. Metabolic Alkalosis: an autosomal recessive Autosomal recessive Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal recessive diseases are only expressed when 2 copies of the recessive allele are inherited. Autosomal Recessive and Autosomal Dominant Inheritance disorder that results from mutations in the HSD11B2 gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics that encodes the kidney isozyme 11β-hydroxysteroid dehydrogenase type 2 Type 2 Spinal Muscular Atrophy. Mineralocorticoid excess Mineralocorticoid excess A hereditary disease characterized by childhood onset hypertension, hypokalemic alkalosis, and low renin and aldosterone secretion. It results from a defect in the activity of the 11-beta-hydroxysteroid dehydrogenase type 2 enzyme which results in inadequate conversion of cortisol to cortisone. The build up of unprocessed cortisol to levels that stimulate mineralocorticoid receptors creates the appearance of having excessive mineralocorticoids. Metabolic Alkalosis presents with hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension, hypokalemia Hypokalemia Hypokalemia is defined as plasma potassium (K+) concentration < 3.5 mEq/L. Homeostatic mechanisms maintain plasma concentration between 3.5-5.2 mEq/L despite marked variation in dietary intake. Hypokalemia can be due to renal losses, GI losses, transcellular shifts, or poor dietary intake. Hypokalemia, metabolic alkalosis Alkalosis A pathological condition that removes acid or adds base to the body fluids. Respiratory Alkalosis, and low plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products renin Renin A highly specific (leu-leu) endopeptidase that generates angiotensin I from its precursor angiotensinogen, leading to a cascade of reactions which elevate blood pressure and increase sodium retention by the kidney in the renin-angiotensin system. Renal Sodium and Water Regulation. Diagnosis is made on finding the triad of hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension, hypokalemia Hypokalemia Hypokalemia is defined as plasma potassium (K+) concentration < 3.5 mEq/L. Homeostatic mechanisms maintain plasma concentration between 3.5-5.2 mEq/L despite marked variation in dietary intake. Hypokalemia can be due to renal losses, GI losses, transcellular shifts, or poor dietary intake. Hypokalemia, and suppressed plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products aldosterone Aldosterone A hormone secreted by the adrenal cortex that regulates electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium. Hyperkalemia levels plus an abnormal urinary cortisol-to-cortisone ratio. Management includes aldosterone antagonists Aldosterone antagonists Drugs that bind to and block the activation of mineralocorticoid receptors by mineralocorticoids such as aldosterone. Heart Failure and Angina Medication such as spironolactone Spironolactone A potassium sparing diuretic that acts by antagonism of aldosterone in the distal renal tubules. It is used mainly in the treatment of refractory edema in patients with congestive heart failure, nephrotic syndrome, or hepatic cirrhosis. Its effects on the endocrine system are utilized in the treatments of hirsutism and acne but they can lead to adverse effects. Potassium-sparing Diuretics.