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Sept 28

Shylla T English 83 cards

Cards in this deck (83)

  1. 1Causes of CKD/ ESRDHypertension and diabetes (more) working together can cause chronic kidney disease
  2. 2why Microalbuminuria is imporanta manifestation of Endothelial cell injury
    A risk marker for:
    Hypertension progression
    Cardiovascular disease
    Chronic Kidney disease
  3. 3Major histologic changes in diabteitc nephropathy:GBM thickening
    Mesangial expansion
    Kimmelstiel-Wilson lesion
    Glomerular sclerosis
  4. 4Clinical diagnosis of dibetic nephopthyDuration of diabetes
    Uncontrolled diabetes
    Proteinuria
    Renal failure
    Retinopathy and Neuropathy
  5. 5Therapy - Slowing the Progression of CKDRAAS suppression/Albuminuria therapy
    ACE inhibitors
    Angiotensin Receptor Blockers
    Hypertension Control
    Diabetes Management (most imporant)
    Hyperlipidemia Control
    Discontinue smoking
  6. 6ManagementTight glycemic control - HbA1C <7% (MOST EFFECTIVE at slowing CKD progression)
    ACEI / ARB treatment - Proteinuria <500 mg/day
    Additional antihypertensive therapy - BP <130/80 mm Hg (<125/75 mmHg in patients with proteinuria > 1.0 g/day)
    Dietary protein restriction - 0.8 g/kg/day
    Lipid lowering therapy - LDL cholesterol <100 mg/dL
    Lifestyle modification - Smoking cessation, weight loss, salt restriction
  7. 7Why are ace and arb goodGlycosolated is damigming afferent and efferent arteior which cause dilation and likiness and aff artiole which will underperfusion kindey which will increase RAAS system
    Which will cause it damaged efferent arteriole and cause vaconstiction and back pressure on glomerulus which dmages ait even more and more leaky
    Ace and arb will decrease efferent arteiolr vasocontrciton becus ace and arb will inhibit RAAS. Yes it will decrease GFR but sacrifice needs to be done
  8. 8Pathology Hypertensive NephrosclerosisPartial hyalinization of glomerulus
    Hylanization in artieal walls
  9. 9Clinical features for hypetensive nephrocoloisisChronic hypertension
    Left ventricular hypertrophy
    Hypertensive retinopathy
    Proteinuria (usually less than 1 gm/day)
    Progressive renal insufficiency
  10. 10mad cycleHyptension will damage ckd which will cause kindey to increase RAAS system which will even cause more hypertension
  11. 11Anemia of CKDUsually normochromic and normocytic
    Erythropoietin due to renal mass
    Must exclude all non-renal causes of anemia
  12. 12Anemia of chronic diseaseDecrease release of iron from macrohpages and decrease of iron reab which will lead to anemia of chronic disease.
    Just cant say its epo and sometimes pt needs iron
  13. 13Mineral bone disordersVitamin D deficiency
    Hypocalcemia
    Hyperphosphatemia
    Hyperparathyrodism
  14. 14PTH releaseincrease phosporus
    decrease calcium
    decrease in vitamin D
  15. 15Clinical featuresAsymptomatic
    Bone pain
    Proximal myopathy
    Fractures
    Vascular medial wall calcification
    Soft tissue calcification
    Calciphylaxis
  16. 16TreatmentLow phosphate diet
    Phosphate binders with meals
    Vitamin D
    Calcimimetic agents
    Parathyroidectomy
  17. 17HemodialysisSurgery that creates vein and arteries together (fistula)
    But since we need right now we put central venous cather in internal jugular vein and tunnel it under collar bone.
    usually on it 3x a weeks
    Take blood out of body and tken into pump and goes thru dialyzer and then once u clean the blood it goes back to body
  18. 18Peritoneal dialysisFluid is put in for hours and then use peitenoem to create ceoncentation gradient.
    Bath has low k and and vessels are exposed to it and they will go down their coencentration gradient out into another bag
  19. 19Renal transplantationWe don’t take out native kindey so u actually have 3rd kidney,
  20. 20What were the risk factors for progression of CKD for our patient?Uncontrolled Hypertension
    Uncontrolled Diabetes
    Heavy Proteinuria
    Hyperlipidemia
    Inconsistent Use ACEi/ARB
    Anemia
    Poor Follow-up & Follow-through
  21. 21Austodomal dominaant polyscitic kidney disease has what?Two renal cysts unilaterally or bilaterally before age 30 years by renal ultrasound.
    Two cysts in each kidney between the ages of 30 and 59 years by renal ultrasound.
    Four or more cysts in each kidney after age 60 years by renal ultrasound.
  22. 22Types of ADPKDPKD1 (more common)
    PKD2 (less common)
    difference bwteen 2 is done by genetic testing
  23. 23Pathogenesis of ADPKDLoss of ciliary signaling which effects cell division
    Cilia is filled with fluid thru aqp2 which leads to fluid filled cysts
  24. 24Extra renal manifestationscysts in liver
    valve abnormailites
    diverticular disease in colon
    anurysm in CNS
  25. 25Progression of ADPKDThe more cyst u have the more decrease in kidney function
  26. 26Treatment of ADPKDdrugs that will block V2 receptors (antagonists) that can slow cysts being made
    more studies need to be done
  27. 27Screening for Intracrianl anuerymsPatients with a family history of SAH
    High risk occupation such as pilots
    Prior to major elective surgeries with anticipated hemodynamic instability.
  28. 28Treatment of asymptomatic ICAUnder 10 mm in diameter - Observation and follow-up (at 6 months initially and then yearly)
    For >10 mm - surgical clipping is indicated.
  29. 29Differential Diagnosis of cystic kindey disease.
  30. 30Stages of CKDI
    II
    III
    IV
    V
  31. 31IKidney Damage
    GFR >90
  32. 32IImild
    60-89
  33. 33IIImoderate
    30-59
  34. 34IVsevere
    15-29
  35. 35VEnd-Stage Renal Disease
    <15
  36. 36End-Stage Renal Disease treatmentstransplant
    dialysis
    hospice
  37. 37Diabetic Nephropathy in stage 1Hyperfunction & Hypertrophy
    Glomerular Hyperfiltration
    GFR
    albumin excretion <30
    timing: present at the time of diagnosis
  38. 38DN in stage 2silent stage
    Thickened BM & expanded mesangium
    GFR
    alumin excetion <30
    timing: First Five years
  39. 39DN in stage 3Incipient Stage
    Microalbuminuria
    GFR
    album excretion 30-300
    timing 6-15 years
  40. 40DN in stage 4Overt Diabetic Nephropathy
    Macroalbuminuria
    GFR
    album excre >300
    timing 15-25 years
  41. 41DN in stage 5Uremic
    ESRD
    GFR is 0
    album ecretion decreasing
    timing: 25-30 years
  42. 42Microalbuminuria24 hr mcg/min
    20-200
    24 hr mg/day
    30-300
  43. 43Macroalbuminuria24 hr mcg/min
    >200
    24 hr mg/day
    >300
  44. 44Kindey USHyper-white/lighter/brighter due to scar tissue
    Brighter then liver means CKD
  45. 45hypertensive nephorsclerosis causesSalt can cause hypetension
    Nsaids
    Lower socionemoic status not having good food
    Genetic
    all can lead to end stage renal disease
  46. 46Pathology Hypertensive NephrosclerosisPartial hyalinization of glomerulus
    Hylanization in arterial walls
  47. 47what can be found in stage 2hypertension
  48. 48what can be found in stage 3PTH
    anemia
    phosphorus
  49. 49what can be found in stage 4acidosis
    hyperkalemia
  50. 50what can be found in stage 5uremic syndrome
  51. 51Co-Occurrences of CKDAlbuminuria
    Anemia of CKD
    CVD
    CKD-MBD
    Hyperglycemia
    Hyperlipidemia
    Hypertension
  52. 52How do we measure Kidney FunctionEstimated GFR (ml/min/1.73m2) MDRD
    Less accurate when GFR is less than 60
    CKD-EPI GFR- Increased accuracy for eGFR evven when GFR 60<
  53. 53Stage 1 and 2 is pretty normal GFR so to tell if you're actually in stage 1 or 2 u need tohave microscopic hematuria
    proteinuria,
    change in kidney US.
    U need to have 1 of these things for 3 months to say of have chronic kidney disease that.
    Unless you have GFR less than 30 then u don’t have to have any of these things
  54. 54Polycystic Kidney Disease (PKD)Gradually developing clusters of non-cancerous fluid-filled sacs in the kidney (renal cysts)
    Accounts for 5-10% of ESRD
    Prevalence: 1 in 500-2000 (~0.5 M in US)
    Multisystem disease with extrarenal manifestations
    Predominantly genetic etiology in most patients
  55. 55Multisystem disease with extrarenal manifestations:liver (hepatic cysts, fibrosis)
    - blood vessels (intracranial aneurysm)
    - heart valves
  56. 56Large phenotypic variability in:age of onset
    rate of progression to ESRD
    extrarenal manifestations
  57. 57Complications:hypertension
    - loss of kidney function (CKD)
    - pain in back or flank
    - hematuria
    - urinary tract infections
  58. 58Genetic vs non-genetic (i.e. environmental) factors have variable contributions in the determination of traits and diseases. Non-genetic factors in PKD- toxic kidney injury
    - smoking
    - caffeine
    - obesity
  59. 59PKD is predominantly what type of genetic?monogenic
    Single rare variant with strong effect causes disease
  60. 60Autosomal Dominant PKD (ADPKD)More common and less severe form
    (prevalence: 1 in 500-2,000)
    Typically adult onset (“adult PKD”)
    Hypertension in most adult patients
    ICA in ~10% of patients
    ESRD in 50% of patients by 60 y
    Mutations in PKD1 (80%), PKD2 (15%)
    and other genes (rare)
  61. 61Autosomal Recessive PKD (ARPKD)Rare and more severe form
    (prevalence: 1 in 20,000-30,000)
    Typically pediatric onset (“juvenile
    PKD”)
    30-50% neonatal mortality
    (due to pulmonary hypoplasia)
    Hypertension in 75% of children
    ESRD in 60% of patients by 20 y
    Mutations in PKHD1 (>90%) and
    other genes
  62. 62Monogenic can be inherited bydominate or recessive fashion
    in this case its mostly dominant
  63. 63ADPKD is caused by mutations in thePKD1 (80% of cases) or PKD2 (15% of cases) genes or, in rare cases mutations in other genes. This demonstrates locus heterogeneity in ADPKD.
    Locus heterogeneity: mutations at different loci (i.e. genes) result in the same phenotype/disease.
  64. 64gentic effectPolycystin-1 (PC1, encoded by PKD1) and polycystin-2 (PC2, encoded by PKD2) are plasma membrane proteins and interact with each other to form a Ca2+-channel
  65. 65Impaired ciliary function in ADPKDCilia are microtubule-based cellular organelles protruding from the cell surface in most polarized cells types of the body. Their primary function is to transmit extracellular signals to the cell (“cells’ antennae”)
    The PC1-PC2 complex is localized to cilia, and involved in cellular mechanosensation.
    In normal cells, fluid-induced ciliary bending activates the PC1-PC2 complex and triggers Ca2+ influx and intracellular Ca2+ signaling, which regulates tissue morphogenesis.
  66. 66PKD mutation effect on pc1 and pc2In PKD, impaired ciliary Ca2+ signaling results in disoriented cell divisions and cyst formation.
    Diseases associated with impaired ciliary function, including PKD, are called ciliopathies.
  67. 67PKD1 mutations cause more severe disease (ADPKD1, type 1) than mutations in PKD2 (ADPKD2, type 2):- more cysts at earlier age
    - faster increase in total kidney volume
    - earlier age of onset of ESRD
    - less overall survival
  68. 68major cause of phenotypic variability in ADPKD.Locus heterogeneity
  69. 69*In addition to in C-terminal truncation, premature termination codons (PTC) also cause mRNA degradation (except when PCT occurs within or close to the last exon). This mechanism is callednonsense-mediated mRNA decay (NMD). NMD leads to reduced protein expression.
    coding variants
  70. 70Allelic heterogenity in ADPKDAllelic heterogeneity: different mutations (i.e. alleles) within the same gene result in the same phenotype/disease.
    The large number of PKD1 mutations (>2,000) in patients demonstrates allelic heterogeneity in ADPKD. Most mutations are private (i.e. only seen in 1 patient). PKD2 (not shown) has >200 mutations.
    Extensive allelic heterogeneity suggests loss-of-function mechanism.
  71. 71part 2The dominant inheritance of loss-of-function mutations indicates haploinsufficiency (1 wild-type allele is not sufficient for normal function).
    Mutations in red lead to C-terminal truncation of the PKD1 protein. Protein-truncating (PT) mutations completely abolish PKD1 function (null-mutations). Non-truncating (NT) mutations shown in green result in incrementally reduced PKD1 function (hypomorphic mutations).
  72. 72Patients with protein-truncating (PT) mutations in PKD1 (PKD1PT) exhibitmore severe phenotype than those with non-truncating (NT) mutations (PKD1NT).
    Allelic heterogeneity is a major cause of phenotypic variability in ADPKD.
  73. 73Variable expression in ADPKDVariable expression: variable phenotype/disease severity in patients with the same genotype (i.e. members of the same family)
    Large intrafamilial variability in ADPKD phenotype (i.e. age of renal death)
  74. 74Modifier genes in ADPKD lead toPhenotypic variability
    Phenotypic variability is greater in non-twin siblings (~50% identical genome) than in monozygotic (MZ) twins (100% identical genome).
    This indicates the effect of genes other than PKD1 (i.e. modifier genes) on the phenotype.
    The identity of modifier genes in ADPKD remains poorly understood.
  75. 75Somatic mutations in ADPKD lead tophenotypic variability
  76. 76Severity of the disease is determined bythe cellular amount of PKD1 activity.
    Most patients carry an inherited hypomorphic (PKD1NT) or null-mutation (PKD1PT) on one allele of PKD1 (i.e. heterozygous).
    An additional somatic mutation on the other PKD1 allele (compound heterozygosity) can further reduce cellular PKD1 activity and exacerbate the phenotype.
  77. 77The presence/absence and nature (i.e. degree of hypomorphy) of somatic mutations is a source of phenotypic variability in ADPKD.
  78. 78Autosomal recessive PKD (ARPKD)>90% of patients have mutations in the Polycystic Kidney and Hepatic Disease 1 (PKHD1) gene.
    In rare cases, mutations in other genes are responsible (locus heterogeneity).
    Fibrocystin (the protein product of PKHD1) localizes to the ciliary membrane and forms a complex with PC1-PC2. The molecular function of fibrocystin remains unknown
  79. 79Most ARPKD patients harborrare, compound heterozygous mutations.
  80. 80Large phenotypic variability in neonatal mortality (30%) and disease progression is due to:locus heterogeneity
    - allelic heterogeneity (truncating mutations:
    neonatal mortality (30-50%) vs non-truncatin mutations: milder presentation, survival)
  81. 81Why do we want to know the genetic determinants of PKD in a patient?Provide better clinical prognosis
    Assess risk of disease recurrence in families
    Treat based on patient’s genotype
    (“personalized medicine”)
  82. 82Predicting Renal Outcomes in ADPKD (PROPKD)The PROPKD score allows the prediction of disease progression in ADPKD based on clinical and genetic characteristics.
    Limitations: not informative in patients <35 y (unless earlier onset of HTN and urologic events); requires genetic testing
  83. 83Risk of PKD recurrenceIn most cases (85%) of ADPKD, the patient has a positive family history (FH). In the absence of FH (15% of cases), ADPKD is due to a de novo mutation in the father’s sperm.
    In populations with low level of consanguinity, patients with ARPKD have no FH.

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Flashcards on Sept 28, created by Shylla T on 28/09/2020.
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