Medicine Marrow Pg No 725-734 (Nephrology)
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Questions and Answers

What is the primary cause associated with Chronic Kidney Disease (CKD)?

  • Large Vessel Disorders
  • Drug-induced Acute Interstitial Nephritis
  • Chronic Tubulointerstitial Fibrosis (correct)
  • Acute Kidney Injury

    • Vascular disorders make up 85% of causes related to renal diseases.

    False

    What term describes blood vessel damage caused by small vessel disorders?

    Thrombotic Microangiopathy

    Acute Kidney Injury (AKI) can develop over a period of ______.

    <p>hours to days</p> Signup and view all the answers

    Match the renal disease category with its associated factor:

    <p>Acute Tubular Necrosis (ATN) = Ischemia-related Renin-Angiotensin-Aldosterone System (RAS) = Large Vessel Disorders Drug-induced Acute Interstitial Nephritis (AIN) = Hypersensitivity Chronic Tubulointerstitial Fibrosis = Chronic Kidney Disease</p> Signup and view all the answers

    What is the primary blood supply source for the renal cortex?

    <p>Renal artery</p> Signup and view all the answers

    The medulla receives a rich blood supply directly from the renal artery.

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

    What vessel connects the afferent arterioles to the glomerular capillary plexus?

    <p>Afferent arteriole</p> Signup and view all the answers

    The main function of the __________ is to facilitate filtration in the kidney.

    <p>glomerular capillary plexus</p> Signup and view all the answers

    Match the following components of renal circulation with their functions:

    <p>Segmental arteries = Branch from the renal artery Afferent arterioles = Supply glomerulus Peritubular capillary plexus = Surround nephron tubules Interlobular vein = Drain blood from cortex</p> Signup and view all the answers

    What effect does the constriction of the afferent arteriole have on the Glomerular Filtration Rate (GFR)?

    <p>Decreases GFR</p> Signup and view all the answers

    Dehydration caused by vomiting can result in pre-renal failure.

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

    What cells in the juxtaglomerular apparatus produce renin?

    <p>JG cells</p> Signup and view all the answers

    ____ is characterized by the loss of intravascular volume leading to decreased glomerular hydrostatic pressure.

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

    Match the following components of the juxtaglomerular apparatus with their functions:

    <p>Macula Densa = Senses decreased sodium and chloride levels Renin = Regulates blood pressure JG Cells = Produce renin Prostaglandins = Mediates dilation of afferent arteriole</p> Signup and view all the answers

    What is the primary defect in Gitelman's Syndrome?

    <p>Na+-Cl- symport</p> Signup and view all the answers

    Gitelman's Syndrome is associated with hypercalciuria.

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

    What clinical feature is commonly observed in Gitelman's Syndrome due to magnesium absorption issues?

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

    Individuals with Gitelman's Syndrome experience _____ levels of potassium in the blood.

    <p>mild hypokalemia</p> Signup and view all the answers

    Match the clinical features with the correct syndrome:

    <p>Polyuria = Gitelman Syndrome Dehydration = Bartter Syndrome Hypomagnesemia = Bartter Syndrome Salt water retention = Gitelman Syndrome</p> Signup and view all the answers

    What is the normal range for Glomerular Filtration Rate (GFR)?

    <p>90 - 125 ml/min</p> Signup and view all the answers

    A GFR of less than 15 ml/min indicates End Stage Renal Disease.

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

    What formula is used to calculate GFR?

    <p>GFR = Net ultrafiltration pressure × ultrafiltration coefficient</p> Signup and view all the answers

    The net ultrafiltration pressure is the difference between _____ and _____.

    <p>Net Hydrostatic Pressure, Net Oncotic Pressure</p> Signup and view all the answers

    Match the following GFR values with their condition:

    <p>GFR &lt; 15 ml/min = End Stage Renal Disease (ESRD) GFR 60-89 ml/min = Stage 2 CKD GFR 30-59 ml/min = Stage 3 CKD GFR 90-125 ml/min = Normal Kidney Function</p> Signup and view all the answers

    What is the diameter of the fenestration slits in the capillary endothelium?

    <p>50-100 nm</p> Signup and view all the answers

    The presence of podocalyxin on the surface of fenestration slits repels negatively charged proteins.

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

    What condition is characterized by microhematuria and minimal proteinuria?

    <p>Post Streptococcal Glomerulo Nephritis (PSGN)</p> Signup and view all the answers

    The effective diameter of proteins larger than _____ mm is generally prevented from passing through the filtration barrier.

    <p>8-10</p> Signup and view all the answers

    Match the following terms with their correct descriptions:

    <p>Fenestration Slits = 50-100 nm diameter, coated in podocalyxin Albumin = 7.6 mm, negatively charged TGF-β = Caused by tubulotoxicity Tubulointerstitial fibrosis = Result of TGF-β formation</p> Signup and view all the answers

    What is the primary function of podocytes in the filtration process?

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

    Angiotensin II stimulates podocyte integrity.

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

    What happens when there is downregulation of nephrin?

    <p>Loss of podocyte integrity</p> Signup and view all the answers

    The diameter of the slit diaphragm is between _____ nm.

    <p>30-50</p> Signup and view all the answers

    Match the following proteins to their respective functions:

    <p>Podocin = Prevents protein leakage Nephrin = Maintains podocyte integrity TRPC6 = Ion channel function CD2AP = Facilitates podocyte stability</p> Signup and view all the answers

    Which inheritance pattern is associated with the defect Nephrin in Congenital Nephrotic Syndrome?

    <p>Autosomal Recessive</p> Signup and view all the answers

    Diffuse mesangial sclerosis (DMS) is associated with 100% mortality at birth.

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

    What is the management option for patients with Steroid-resistant FSGS?

    <p>Renal transplant</p> Signup and view all the answers

    Finnish type nephrotic syndrome is most commonly seen in __________ babies.

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

    Match the following renal diseases to their corresponding histological features:

    <p>DMS = Diffuse mesangial sclerosis FSGS = Focal segmental glomerulosclerosis IgA nephropathy = Mesangial deposition of IgA Alport syndrome = Thinning and splitting of the GBM</p> Signup and view all the answers

    What is the primary defect associated with Alport syndrome?

    <p>Defect in Type 4 collagen</p> Signup and view all the answers

    The normal thickness of the glomerular basement membrane (GBM) is between 350 nm to 400 nm.

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

    What major components contribute to the negative charge of the glomerular basement membrane (GBM)?

    <p>Heparin sulfate proteoglycans</p> Signup and view all the answers

    In thin GBM disease, the thickness of the GBM is less than ______ nm.

    <p>200</p> Signup and view all the answers

    Match the following components with their related functions:

    <p>Mesangial cells = Supporting cells of the filtration barrier Masson's Trichrome = Staining technique for visualization IgA nephropathy = Most common prototype glomerular disease Heparin sulfate proteoglycans = Contribute to negative charge of GBM</p> Signup and view all the answers

    Which of the following cells are NOT a component of the juxtaglomerular apparatus?

    <p>Glomerular cells</p> Signup and view all the answers

    The macula densa primarily functions through the release of adenosine to regulate the afferent arteriole.

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

    What is the result of impaired reabsorption of solute and water during the phases of tubular injury?

    <p>Decreased Glomerular Filtration Rate (GFR)</p> Signup and view all the answers

    The macula densa is located in the cortical portion of the thick ascending limb of the loop of Henle and is composed of __________ cells.

    <p>modified tall columnar</p> Signup and view all the answers

    Match the phases of tubular injury with their descriptions:

    <p>Phase 1 = Duration &lt; 24 hours, renal tubular injury Phase 2 = Impaired reabsorption, macula densa senses solute load Phase 3 = Release of adenosine, constriction of afferent arteriole Phase 4 = Findings include ↓GFR and ↑s.creatinine</p> Signup and view all the answers

    Study Notes

    Renal Diseases

    • Tubules and Interstitium (85% of the kidney)
      • Acute Kidney Injury (AKI) can occur over hours or days
      • Chronic Kidney Disease (CKD) is associated with Chronic Tubulointerstitial Fibrosis/disease & Renal Tubular Acidosis (RTA) type 4
    • Vascular (5% of the kidney)
      • Large Vessel Disorders often caused by renal artery stenosis, are linked to Renin-Angiotensin-Aldosterone System (RAS) activation
      • Small Vessel Disorders lead to Thrombotic Microangiopathy (TMA), a condition involving blood vessel damage
      • Ischemic Nephropathy is a result of a hypertensive crisis, potentially progressing from smaller blood vessel disorders
    • Other Factors
      • Ischemia-related Acute Tubular Necrosis (ATN)
      • Drug-induced Acute Interstitial Nephritis (AIN) (hypersensitivity)

    Renal Circulation

    • Renal Artery → 5 segmental arteries (4 anterior + 1 posterior) → Interlobar artery → Arcuate artery → Interlobular artery → Afferent arteriole → Glomerular capillary plexus (in cortex) → Efferent arteriole → Peritubular capillary plexus → Venule → Interlobular vein → IVC (Inferior vena cava)

    Cortex vs. Medullary Blood Supply

    • Cortex is supplied by the renal artery
    • Medulla is supplied by the vasa recta
    • Cortex has good blood supply
    • Medulla has poor supply, particularly the pars recta/proximal straight tubule, which is most vulnerable to hypoxia

    Juxtaglomerular Apparatus

    • Phases of tubular injury:
      • Management (mx): Supportive care, Monitor fluid intake (↑ chance of edema due to renal failure)
      • Pre-renal Failure: Dehydration (e.g., ↑ vomiting), Loss of intravascular volume, ↓ glomerular hydrostatic pressure, ↓ GFR (Glomerular Filtration Rate), ↑ serum creatinine
      • Recovery Phase:
    • Mechanism of Action (MOA):
      • Angiotensin II constricts the afferent arteriole ↓GFR
      • Angiotensin II prevents further salt + H₂O loss due to impaired reabsorption
      • Angiotensin II ↑ Serum creatinine
    • Macula Densa and JG Cells
      • Macula Densa senses ↓ Na+/Cl+/K+ and ↑ proximal tubular absorption, leading to dilatation of the afferent arteriole (mediated by prostaglandins) and ↑GFR
    • JG Cells
      • Composition: Granular cells
      • Site: Tunica media of afferent arteriole > efferent arteriole
      • Function: Produce renin

    Distal Convoluted Tubules

    • Physiology
      • Sodium (Na+Na^+Na+), Chloride (Cl−Cl^-Cl−) and Potassium (K+K^+K+) ions are transported through a Na+−Cl−Na^+-Cl^-Na+−Cl− symport in the distal convoluted tubules

    Gitelman's Syndrome

    • Adults
      • Defect: Na+−Cl−Na^+-Cl^-Na+−Cl− Symport
      • Clinical Features:
        • Normal renal function tests
        • Mild hypokalemia, alkalosis, and polyuria due to less salt and water depletion
        • Failure to thrive
        • Reduced magnesium (Mg2+Mg^{2+}Mg2+) absorption leading to hypomagnesemia (100% of cases)
        • No hypocalciuria (no stones)
        • No hypermagnesemia

    Bartter vs Gitelman

    FeatureBartter SyndromeGitelman SyndromePolyuriaMoreLessPolydipsiaMoreLessDehydrationMoreLessTetanyMoreLessGrowth RetardationMoreLessSalt Water RetentionMoreLessUrine Ca2+Ca^{2+}Ca2+MoreLessNephrocalcinosisMoreLessHypomagnesemiaMoreLessIn 20% cases (Type V Bartter)MoreLow

    Glomerular Filtration Rate (GFR)

    • Definition: Amount of urine filtered by all nephrons in both kidneys in one minute
    • Calculation: GFR = Net ultrafiltration pressure × ultrafiltration (UF) coefficient
      • Net ultrafiltration pressure = [Net Hydrostatic Pressure (H.P) - Net Oncotic pressure (O.P)]
      • Normal GFR: 90 - 125 ml/min
      • GFR < 15 ml/min: GS/End Stage Renal Disease (ESRD)/uremic phase (Dialysis required)
      • CKD is classified based on the GFR

    Glomerulus - Anatomy

    • Filtration Barrier
      • Capillary Endothelium with Fenestrations
        • Fenestration Slits: 50-100nm diameter, coated in podocalyxin (negative charge), prevents proteinuria (albuminuria), preventing nephrotoxicity
      • Glomerular Basement Membrane (GBM)
        • Constituent: Type 4 collagen (majorly)
        • Type 4 collagen defect leads to Alport syndrome
        • Visualization of GBM using Electron m/s (microscope) or Stains under light m/s (Gomori methenamine Silver Stain, Masson's Trichrome)
        • Normal thickness: 350-400nm
        • Thin GBM disease: < 200nm
        • Supporting cells of the filtration barrier: Mesangial cells (constituent: microfilaments; violent contraction, rupture of capillary → macrohematuria, ↓ surface area → ↓ GFR, mesangial cell/mesangial proliferative (>3 mesangial cells in a space)/mesangial cell expansion (matrix expansion)/ glomerular disease: IgA nephropathy (m/c) prototype disease)
      • Slit Diaphragm/Filtration Slits
        • Podocytes: terminally differentiated cells (cannot be regenerated), anchored to the GBM by foot processes, do not allow filtration, inside: actin 4, proteins: podocin, TRPC6
        • Diameter: 30-50nm, coated with podocalyxin
        • Function: Filtration
        • Nephrins: Proteins in the slit diaphragm preventing protein leakage, maintain podocyte integrity
        • Angiotensin: Binds to podocyte containing angiotensin II binding receptor
        • Downregulation of nephrin: leads to loss of podocyte integrity (Podocytopathies)
        • Podocyte detachment: leads to podocyturia
        • Podocytopenia: leads to GBM attaches to parietal epithelial cells
        • Synechiae formation: leads to glomerulosclerosis → CKD (Chronic Kidney Disease)

    Congenital Nephrotic Syndrome: DMS: Diffuse Mesangial Sclerosis

    InheritanceDefectAgeOutcomeHistologyManagementARNephrin : NPHS₁Birth100% mortality= DMS-ARPodocin3-5 years100% Steroid resistance= FSGSRenal transplantADα - actinin 4/TRP 6Adolescence100% Steroid resistance= FSGSRenal transplant

    • Note: Finnish type nephrotic syndrome is most commonly seen in premature babies with large placentas.
    • DMS is also seen in Denys Drash Syndrome.

    Juxtaglomerular Apparatus (JGA)

    • Components:

      • Juxtaglomerular (JG) cells
      • Macula densa
      • Mesangial/Lacis/Supporting cells/Polkissen cells

    • Macula Densa & JG Cells

      • Composition: Modified tall columnar cells
      • Site: Cortical portion of the thick ascending limb of loop of Henle (TAL)/distal straight tubule
      • Function: Tubulo glomerular (TG) feedback (mediated by adenosine)
      • Applied Aspect of TG Feedback: Sequence of Tubular Injury
        • Phase of tubular injury ( < 24 hours): Renal tubular injury (tubulotoxic drugs e.g. Gentamicin) → PC injury → ↓reabsorption of solute + H₂O
        • Phase of TG feedback: Impaired reabsorption of solute + H₂O → macula densa senses Cl > K > Na⁺ load delivered to TAL → Release of adenosine → Constrict afferent arteriole
        • Findings of TG feedback phase: ↓GFR, ↑s.creatinine, ↑K⁺ → Cardiac arrhythmias, ↑H⁺ → metabolic acidosis

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    Description

    This quiz explores the key concepts of renal diseases, focusing on Acute Kidney Injury (AKI) and Chronic Kidney Disease (CKD), as well as vascular disorders affecting the kidneys. Understand the implications of ischemic nephropathy, drug-induced conditions, and renal circulation. Test your knowledge on the kidney's critical functions and dysfunctions.

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