Medicine Marrow Pg No 815-824 (Acid-Base Regulation)
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Medicine Marrow Pg No 815-824 (Acid-Base Regulation)

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Questions and Answers

Which of the following conditions is associated with distal RTA?

  • Severe hypokalemia (correct)
  • Glycosuria
  • Severe hyperkalemia
  • Normal urine pH

    • Urinary anion gap (UAG) in distal RTA is typically positive.

    False

    What is the primary defect in distal Renal Tubular Acidosis (RTA)?

    H+ ATPase / H+K+ ATPase defect

    In distal RTA, the urine pH is generally ________.

    <p>alkaline</p> Signup and view all the answers

    Match the following characteristics with the type of RTA:

    <p>Severe NAGMA + Hypokalemia = Distal RTA Glycosuria present = Proximal RTA Kidney stones = Distal RTA Mild Rickets = Proximal RTA</p> Signup and view all the answers

    What is a primary cause of Chronic Kidney Disease?

    <p>Diabetic Kidney Disease</p> Signup and view all the answers

    Viable nephrons can be regenerated after birth.

    <p>False</p> Signup and view all the answers

    What is the consequence of a decrease in the number of viable nephrons in Chronic Kidney Disease?

    <p>Intraglomerular hypertension and proteinuria.</p> Signup and view all the answers

    The primary determinant of renal function decline in Chronic Kidney Disease is the ________.

    <p>tubulointerstitium</p> Signup and view all the answers

    Match the following causes of Chronic Kidney Disease with their descriptions:

    <p>Diabetic Kidney Disease = Most common cause, worst prognosis Chronic Glomerulonephritis = A group of diseases causing inflammation of the glomeruli Ischemic nephropathy = Caused by reduced blood flow to the kidneys Adult polycystic kidney disease = A genetic disorder causing cyst formation in kidneys</p> Signup and view all the answers

    Which GLP-1 receptor agonist does not require dose adjustment?

    <p>Liraglutide</p> Signup and view all the answers

    All DPP-4 inhibitors require dose adjustment for patients with reduced kidney function.

    <p>False</p> Signup and view all the answers

    Name three drugs that are considered renal safe.

    <p>Insulin, Glipizide, Gliclazide</p> Signup and view all the answers

    The drug __________ is known as an oxidative phosphorylation blocker and is safe in CKD.

    <p>Imeglimin</p> Signup and view all the answers

    Match the following drugs with their characteristics:

    <p>Liraglutide = Most preferred GLP-1 receptor agonist Linagliptin = Most preferred DPP-4 inhibitor, no dose adjustment Glipizide = Renal safe sulfonylurea Semaglutide = Oral GLP-1 receptor agonist</p> Signup and view all the answers

    Which of the following causes is most common for Renal Tubular Acidosis type 2 in childhood?

    <p>Cystinosis</p> Signup and view all the answers

    The defect in Proximal Convolutional Tubule (PCT) leads to hyperkalemia.

    <p>False</p> Signup and view all the answers

    What is the primary defect associated with Renal Tubular Acidosis type 2?

    <p>Na+ - HCO3− exchanger defect</p> Signup and view all the answers

    For every 1 mEq of reabsorbed $HCO_3^−$, ______ mEq of $H^+$ is utilized.

    <p>1</p> Signup and view all the answers

    Match the following causes with the appropriate age group:

    <p>Cystinosis = Childhood Myeloma = Adults Wilson disease = Adolescence Fanconi's syndrome = Childhood</p> Signup and view all the answers

    Which of the following is a risk factor for Diabetic Kidney Disease (DKD)?

    <p>Type 1 diabetes mellitus (T1DM)</p> Signup and view all the answers

    Albuminuria levels of >300 mg/g indicate a normal condition.

    <p>False</p> Signup and view all the answers

    What is the recommended screening schedule for diabetic patients at risk of DKD?

    <p>Every 5 years, or at diagnosis/within 3-6 months.</p> Signup and view all the answers

    Factors causing a net increase of efferent arteriolar resistance include angiotensin II and _________.

    <p>Thromboxane A2</p> Signup and view all the answers

    Match the following conditions with their corresponding albuminuria levels:

    <p>Normal = &lt; 30 mg/g Microalbuminuria = 30-300 mg/g Albuminuria = &gt; 300 mg/g</p> Signup and view all the answers

    What is the primary role of the buffering system in the body?

    <p>To maintain acid-base balance</p> Signup and view all the answers

    A strong acid is considered a better buffer than a weak acid.

    <p>False</p> Signup and view all the answers

    What is the pH level associated with normal blood $H^+$ concentration?

    <p>7.4</p> Signup and view all the answers

    The primary extracellular buffering system is based on the reaction between $[H^+]$ and $[HCO_3^-]$ to form __________.

    <p>H2CO3</p> Signup and view all the answers

    Match the following buffering systems with their response times:

    <p>Chemical = Immediate response Respiratory = Fast response Renal = Slow response</p> Signup and view all the answers

    What is the primary buffer system in metabolic acidosis?

    <p>HCO3 / H2CO3 system</p> Signup and view all the answers

    A high anion gap indicates normal levels of unmeasured anions in the blood.

    <p>False</p> Signup and view all the answers

    Name two causes of high anion gap metabolic acidosis.

    <p>Ketoacidosis, Lactic acidosis</p> Signup and view all the answers

    The anion gap is calculated using the formula: Na+ - (Cl- + HCO3-), where Na+ is the measured _________.

    <p>cation</p> Signup and view all the answers

    Match the following causes of metabolic acidosis with their corresponding types:

    <p>VIPoma = Normal Anion Gap Metabolic Acidosis Ketoacidosis = High Anion Gap Metabolic Acidosis Renal tubular acidosis = Normal Anion Gap Metabolic Acidosis Salicylate toxicity = High Anion Gap Metabolic Acidosis</p> Signup and view all the answers

    What is the definition of acidemia?

    <p>Blood pH &lt; 7.36</p> Signup and view all the answers

    Non-volatile acids are eliminated through respiration.

    <p>False</p> Signup and view all the answers

    What is the daily excretion rate of non-volatile acid produced by the kidneys?

    <p>1 meq/kg/day</p> Signup and view all the answers

    The renal buffering system primarily excretes _______ acid and ammonia.

    <p>titratable</p> Signup and view all the answers

    Match the following acids with their type:

    <p>Sulfuric acid = Non-volatile acid Phosphoric acid = Non-volatile acid Carbonic acid = Volatile acid H2O = Does not categorize as acid type</p> Signup and view all the answers

    Which feature is characteristic of Class 2 in the Traver et al classification of diabetic nephropathy?

    <p>Mesangial expansion</p> Signup and view all the answers

    Stage V in Mogensen staging is characterized by End Stage Renal Disease (ESRD).

    <p>True</p> Signup and view all the answers

    What is the histological finding associated with diabetic nephropathy?

    <p>Nodular glomerulosclerosis</p> Signup and view all the answers

    Stage 3 of the Traver et al classification is associated with ________ albuminuria.

    <p>macro</p> Signup and view all the answers

    Match the following classes in Traver et al classification with their features:

    <p>Class 1 = GBM thickening Class 2 = Mesangial expansion Class 3 = Nodular sclerosis Class 4 = Advanced diabetic glomerulosclerosis</p> Signup and view all the answers

    What is the main management strategy for diabetic kidney disease?

    <p>Lifestyle modification and blood sugar control</p> Signup and view all the answers

    SGLT2 inhibitors are contraindicated if the GFR is below 20 mL/min.

    <p>True</p> Signup and view all the answers

    List one complication associated with diabetic kidney disease.

    <p>Hypertension</p> Signup and view all the answers

    In patients with Type 2 diabetes, diabetic kidney disease occurs in approximately ________% of patients.

    <p>65</p> Signup and view all the answers

    Match the following drug classes with their characteristics regarding diabetic management:

    <p>SGLT2 Inhibitors = Benefit in heart failure and promote weight loss Metformin = High glucose-lowering efficacy with low hypoglycemia risk DPP-4 Inhibitors = Neutral in weight effects and intermediate efficacy Insulin/Sulfonylureas = Highest glucose-lowering efficacy but high hypoglycemia risk</p> Signup and view all the answers

    Which of the following drugs is first line for proteinuria control?

    <p>SGLT2 Inhibitors</p> Signup and view all the answers

    Metformin should be used when GFR is above 30 mL/min.

    <p>True</p> Signup and view all the answers

    What condition is characterized by swelling due to fluid retention?

    <p>Edema</p> Signup and view all the answers

    Diabetic kidney disease is associated with damage to the ________ and blood vessels in the kidneys.

    <p>tubules</p> Signup and view all the answers

    Which class of drugs has been shown to have a neutral impact on cardiovascular and hypoglycemia risk?

    <p>Metformin</p> Signup and view all the answers

    Study Notes

    Chronic Kidney Disease

    • The decrease in viable nephrons results in intraglomerular hypertension and proteinuria.
    • The number of viable nephrons at birth is fixed, and they can't be regenerated.
    • A decrease in the number of nephrons causes an increase in glomerular hyperfiltration to maintain GFR.
    • High blood pressure inside the glomerulus (intraglomerular hypertension) leads to:
      • Stretching of the capillary pores, leading to increased diameter.
      • Proteinuria, which is toxic to the tubules.
      • Activation of the renin-angiotensin-aldosterone system (RAAS) locally via angiotensin II.
      • Changes in nephrin expression.
      • Mesangial cell proliferation.
    • Glomerular sclerosis (GS) and interstitial fibrosis (IF) with tubular atrophy (TA) contribute to kidney function decline.
    • The tubulointerstitium accounts for 85-90% of the kidney and plays a crucial role in determining renal function decline.
    • Progression of chronic kidney disease is independent of the cause; after 50% of nephrons are destroyed, there is a tendency to worsen.
    • Diabetic kidney disease (DKD) is the most common cause of chronic kidney disease and has the worst prognosis.

    Distal Renal Tubular Acidosis (RTA)

    • A defect in the H+H^+H+ ATPase or H+K+H^+K^+H+K+ ATPase in the distal tubules leads to:
      • Severe non-anion gap metabolic acidosis (NAGMA).
      • Severe hypokalemia.
      • Decreased calcium reabsorption from bone, leading to rickets-like changes and kidney stones.
    • This condition also causes salt-water wasting.
    • The RAAS is activated.
    • Glycosuria is not present.
    • Urine pH is alkaline.

    Distal vs. Proximal RTA

    • Distal RTA is characterized by severe NAGMA and hypokalemia, rickets-like changes, decreased calcium reabsorption, and alkaline urine pH.
    • Proximal RTA is characterized by mild rickets, decreased calcium reabsorption due to phosphorus loss, normal urine pH, and glycosuria.
    • Inherited distal RTA is often due to autosomal recessive inheritance of the H+H^+H+ ATPase or H+K+H^+K^+H+K+ ATPase defect.
    • Acquired distal RTA can be caused by conditions like Sjogren's syndrome, whereas proximal RTA can be caused by Fanconi's syndrome and myeloma.

    Urine Anion Gap (UAG)

    • UAG is calculated as the urinary sodium (Na+) plus the urinary potassium (K+) minus the urinary chloride (Cl-) - it represents the difference between unmeasured anions and unmeasured cations.
    • A slightly negative UAG is typical.
    • A positive UAG suggests RTA, while a negative UAG suggests gastrointestinal losses.

    Medications Safe for Patients with Reduced Kidney Function (eGFRD)

    • GLP-1 receptor agonists are preferred in patients with reduced kidney function; liraglutide is the most preferred, while semaglutide is an oral option, and dose adjustment may be unnecessary.
    • DPP-4 inhibitors are also an option, linagliptin being the most preferred due to its lack of dose adjustment requirements.
    • Sulfonylureas are not preferred, but glipizide and gliclazide are considered renal-safe.
    • Insulin, glipizide, gliclazide, and imeglimin are medications considered safe for use in patients with eGFRD.

    Diabetic Kidney Disease (DKD)

    • 50-60% of diabetic patients develop DKD, with the risk increasing with age.

    • T1DM is an important risk factor for DKD development.

    • Screening for diabetic kidney disease should be performed every 5 years or within 3-6 months of diagnosis.

    • Screening tests include albuminuria checks and 24-hour urine protein tests (cumbersome but superior).

    • Early morning albumin:creatinine ratio (ACR) is a commonly used screening test.

    • Levels of albuminuria are categorized as:

      • < 30 mg/g: Normal

      • 30-300 mg/g: Microalbuminuria

      • 300 mg/g: Albuminuria

    Pathogenesis of DKD

    • There is afferent arterial vasodilation and efferent arterial vasoconstriction, which are believed to be key players in the development of DKD.
    • Factors that reduce afferent arteriolar resistance include:
      • NO bioavailability
      • Prostaglandins
      • Kallikrein-kinins
      • Atrial natriuretic factor
      • Angiotensin (1-7)
    • Factors that increase efferent arteriolar resistance include:
      • Angiotensin II
      • Thromboxane A2
      • Endothelin-1 (ETA receptor)
    • SGLT2 inhibitors are considered a first-line option for the management of hyperfiltration injury associated with DKD.

    Acid-Base Regulation

    • For every 1 mEq of HCO3−HCO_3^−HCO3−​ reabsorption, 1 mEq of H+H^+H+ is used.
    • To reabsorb 4320 mEq of HCO3−HCO_3^−HCO3−​, 4400 mEq of H+H^+H+ is needed, which is not practically possible, highlighting the importance of buffering systems.
    • 80 mEq of non-volatile acid is produced daily.

    Renal Tubular Acidosis (RTA)

    • Renal tubular acidosis type 2 involves a generalized dysfunction of the proximal tubule (PCT).
    • The defect in RTA type 2 lies in either the Na+−HCO3−Na^+ - HCO_3^−Na+−HCO3−​ exchanger or carbonic anhydrase defect.

    Causes of RTA Type 2

    • In childhood, it can be caused by Fanconi's syndrome, cystinosis (most common), Lowe's disease, and Wilson disease.
    • In adults, it can be caused by myeloma or certain medications like tenofovir, cyclophosphamide, outdated tetracycline, and gentamicin.

    Consequences of PCT Defect

    • HCO3- is not reabsorbed, leading to NAGMA.
    • There is salt-water wasting.
    • Arteriolar volume is defective.
    • RAS activation occurs.
    • Hypokalemia is present.
    • In the cortical collecting system, a Na+Na^+Na+ - phosphorus exchange defect occurs, leading to phosphorus loss.
    • Loss of phosphorus can contribute to rickets-like changes.
    • The Na+Na^+Na+ - glucose transporter becomes inactive in the PCT leading to glycosuria.

    Net Acid Secretion

    • Net acid secretion is calculated as the urinary NH4+NH_4^+NH4+​ plus the urinary titratable acid minus the urinary HCO3−HCO_3^−HCO3−​.

    Introduction to Acid-Base Analysis

    • Maintaining acid-base balance is crucial for:
      • Enzyme systems
      • Muscle and nerve function
      • Oxygenation
      • Metabolic processes
    • The body functions within a narrow pH range.
    • The Siggaard-Andersen nomogram helps in acid-base analysis.
    • The human body produces 7 crore nmol of H+H^+H+ per day, with a blood H+H^+H+ concentration of 40 nmol/L (pH 7.4). This excess H+H^+H+ is cellulotoxic and can alter cellular morphology.
    • Buffering systems are essential for safely handling this excess H+H^+H+.

    Buffering System

    • There are three types of buffering systems:
      • Chemical: Immediate response, involving conjugate base and acid.
      • Respiratory: Fast response, involving H+H^+H+ and HCO3−HCO_3^-HCO3−​, forming carbonic acid. This is the most potent extracellular buffering system.
      • Renal: Slow response.

    Chemical Buffering

    • The mechanism of chemical buffering involves the pKa, which is the pH at which the acid state is 50%.
    • Strong acids (pKa < 3) exist mainly in the HA form and are not suitable for basic functions.
    • Weak acids exist primarily in the A− form and are the best buffer systems.

    Metabolic Acidosis

    • Metabolic acidosis can occur due to:
      • Acid generation (exogenous or endogenous).
      • Alkali loss (gastrointestinal and renal losses)

    Anion Gap

    • Anion gap is calculated as the difference between measured cations and measured anions.
    • It represents the unmeasured anions minus the unmeasured cations.
    • Anion gap = Na+ - (Cl- + HCO3-)

    Types of Metabolic Acidosis

    • Normal Anion Gap Metabolic Acidosis (NAGMA): In this type, the HCO3- loss is compensated by Cl- (hyperchloremic acidosis). The common causes are GI loss, or renal loss due to RTA.
    • High Anion Gap Metabolic Acidosis (HAGMA): Increased unmeasured anions are present. Causes include:
      • KUSMAL: (Ketoacidosis: DKA, starvation, alcoholic ketoacidosis)
      • Uremia
      • Salicylates/Paraldehyde
      • Methanol
      • Ethylene glycol
      • Lactic acidosis

    Basic Acid-Base Terminology

    • Acidemia: Blood pH < 7.36
    • Alkalemia: Blood pH > 7.44

    H+ Ion Estimation from pH Values

    • You can estimate H+ ion concentration from pH values using a table or formula (not directly provided in the text).

    Respiratory Buffering System

    • The respiratory system can buffer by increasing CO2 drive out, ultimately leading to respiratory alkalosis.

    Renal Buffering System

    • The kidneys produce non-volatile acids like sulfuric acid and phosphoric acid, which are excreted as titratable acid and ammonia (1 meq/kg/ day = 80 meq/day total).
    • HCO3- is not excreted in urine (except for minimal amounts).
    • HCO3- is 100% reabsorbed in the renal tubules, with the majority of reabsorption occurring in the PCT (approx. 4000 meq).

    Volatile Acids

    • Volatile acids, such as carbonic acid, are converted to water and CO2.
    • CO2 is eliminated through respiration.

    Diabetic Kidney Disease (DKD): Hypertension

    • Hypertension is a common finding in patients with DKD, and its presence in those with albuminuria should alert the clinician to the likely presence of DKD.
    • Edema is frequently encountered due to sodium and glucose transporter issues.
    • Retinopathy concordance is often seen in diabetic patients with hypertension as it affects blood vessels in the eye.

    Non-albuminuric Diabetic Kidney Disease (DKD)

    • This refers to kidney damage specifically affecting the tubules and blood vessels without albuminuria.

    Diabetic Patient with Non-Diabetic Renal Disease

    • If a diabetic patient has renal disease that is not clearly due to diabetes, other causes should be considered.
    • Examples include nephrotic syndrome and renal dysfunction (onset with T2DM).
    • A biopsy is recommended in such cases.

    Diabetic Kidney Disease Causes

    • Hematuria/RBC casts in the urine suggest underlying kidney damage.
    • Extra-renal vasculitis and myeloma can cause renal dysfunction.
    • Rapidly progressive renal failure (RPRF) is a serious condition requiring immediate attention.

    Diabetic Kidney Disease Management

    • Tight blood sugar control is crucial, aiming for glucose levels > 7mg/dL.
    • Hypoglycemia should be avoided.
    • Metformin is recommended if GFR is > 30 mL/min, as it has a neutral impact on cardiovascular and hypoglycemia risks.
    • Lifestyle modifications are essential for effective diabetes and weight management.

    Table of Drugs Used in Diabetes Control

    • The table outlines medications used in diabetes control, highlighting their impact on heart failure, glucose-lowering efficacy, hypoglycemia risk, and weight effects.
    • Important Note:* The table with drug information (not included in the text) provides valuable insight into specific medications for managing diabetes.

    Diabetic Nephropathy (AKA Albuminuric DKD)

    • This condition develops when glomerular filtration rate (GFR) is impaired and there is proteinuria, including a nephrotic range of albuminuria without kidney failure.
    • Micro/macro hematuria is generally absent.

    Classifications of Diabetic Kidney Disease

    • Mogensen Staging: This model was developed for T1DM, but it is not as accurate for T2DM. Stage V represents ESRD (End Stage Renal Disease).
    • Traver et al. Classification: This is a histological classification system that outlines characteristic patterns of kidney damage observed in diabetic kidney disease:
      • Class 1: Earliest finding is GBM thickening. Stage 1: Hyper-filtration with increased GFR.
      • Class 2: Mesangial expansion is the most common finding (90%) with afferent and efferent hyalinosis. Stage 2: Silent or microalbuminuria with either decreased or increased GFR.
      • Class 3: Nodular sclerosis (Kimmelstiel-Wilson lesions). Stage 3: Macroalbuminuria with either decreased or increased GFR.
      • Class 4: Advanced diabetic glomerulosclerosis, and less common (only 50% of patients). Stage 4: Renal impairment with decreased GFR.
    • Note:* The table describing the Traver et al. Classification is included in the text.

    Nodular Kidney Diseases

    • Nodules in the kidneys can be caused by various conditions:
      • Diabetes (Kimmelstiel-Wilson nodules)
      • MPGN (membrano proliferative glomerulonephritis)
      • Lichen deposition
      • Amyloidosis
      • Smokers
      • Other diseases
    • Additional Information:*
    • The text includes images and diagrams that further explain the concepts (not included in the text).
    • The document focuses on understanding the pathophysiology of chronic kidney disease, diabetic kidney disease, and acid-base balance.
    • It provides a framework for screening, diagnosing, and managing these conditions.
    • The text emphasizes the importance of monitoring kidney function (GFR), managing blood sugar levels, and addressing associated complications like hypertension.

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    Test your knowledge on distal renal tubular acidosis and chronic kidney disease. This quiz covers key concepts, consequences, and specific treatments related to RTA and CKD. Assess your understanding of urinary characteristics, drug safety, and the mechanisms behind these renal conditions.

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