Renal A&P and        PathophysiologyReference: Pathophysiology text by Kathryn McCance                            Mindy Mi...
FUNCTIONS   Homeostasis of the internal environment   Maintain fluid and electrolyte balance   Secretion of erythropoet...
Anatomy   Paired organs found    within the retro-    peritoneal space   Parts:       Cortex      Medulla   Supportin...
Anatomy
ANATOMY   NEPHRON       Functional unit of the kidney       Three types:            Superficial cortical            M...
Anatomy   Glomerulus       Afferent arteriole: blood enters the glomerulus       Efferent arteriole: blood leaves the g...
Nephron
Anatomy: Glomerulus
Glomerulus
Glomerular Membrane: Podocytes
ANATOMY   Nephron       Parts            Bowman’s capsule            Proximal tubule            Loop of Henle        ...
Nephron
Blood Supply to the Kidney
ANATOMY   BLOOD SUPPLY       Vasa Recta          Network of capillaries that descend around the           lower portion...
Cortical Nephron
Medullary Nephron
Nephron blood vessels
Renal Blood Flow   Glomerular arterioles        Receives blood from interlobular arteries        High pressure system  ...
Autoregulation   Mechanisms that maintain renal blood flow at    constant pressure between 80-180 mm Hg   Afferent arter...
Autoregulation   Example       If systemic blood pressure increases, there will be        vasoconstriction of the affere...
Control of Renal Blood Flow   Neural Mechanisms       Kidneys are innervated by the sympathetic nervous        system   ...
GLOMERULAR NET FILTRATION   Pressures favoring                  Pressures opposing    filtration                        ...
Filtration Pressures
GLOMERULAR FILTRATION   Filtration Pressure:       Net pressure forcing fluid out of the glomerulus   Factors that affe...
Juxtaglomerular Apparatus   Juxtaglomerular cells:       Specialized cells located around the afferent        arteriole ...
Reabsorption/Secretion   Tubular reabsorption: movement of fluid    and solutes from the tubule to the    peritubular cap...
The Regulation of GFR
PROXIMAL TUBULE   FUNCTIONS:       Reabsorption of electrolytes, water, and non        electrolytes such as amino acids,...
LOOP OF HENLE   Function:       Primary function is the establish a        hyperosmotic state within the medullary      ...
Nephron Functions
Loop of Henle ActivityWater                             NA/CLOut of                            Out ofD Limb               ...
COUNTER CURRENT    Hyperosmolarity of the interstitial fluid of the    medullary of the kidney allows for the presence   ...
Concentration of Urine
DISTAL TUBULE   Final regulator of water balance   Reabsorption of Na, H2O (ADH), HCO3   Secretion of K, Urea, H, drugs
Functions of ADH
Functions of ADH
Overall Renal Function
Renal Hormones   Vitamin D       Diet and UV interaction of cholesterol in skin       Activation of hydroxylation start...
Renal Hormones (cont.)   Erythropoietin       Produced in KIDNEY and stimulates RBC        production in the bone marrow...
Anatomy: Ureters    Muscular tubes that extend from kidney to bladder   Lie retroperitoneal and attached to posterior ab...
Radiographic View of the Urinary            System
Anatomy: Urinary Bladder   Hollow muscular organ that acts as storage    reservoir for urine   Mucosa lining has rugae t...
Anatomy of the Bladder
Micturition Reflex   Stretch receptors are stimulated as the bladder    fills with urine   Urge to urinate at approximat...
Pathophysiology   Finally …   Renal       Systemic disease       Intrinsic   Urinary       Infection       Obstruct...
Obstructive Uropathy   Consequences of obstruction       Hydroureter: obstruction of the ureter with        accumulation...
Sites of Urinary Obstruction
Nephrolithiasis   Kidney Stones: Nephrolithiasis       Types:            Calcium oxylate - alkaline urine            S...
Nephrolithiasis   Calcium stones       Smallest       Increased frequency in middle age men       80% idiopathic     ...
Nephrolithiasis   Kidney Stones       Clinical manifestations:            Pain, Pain, Pain - can have radiating pain to...
Lower urinary tract obstruction   Prostate enlargement   Urethral stricture   Severe pelvic organ prolapse (cystocele)...
Neurogenic Bladder   Dysfunctional filling or emptying   Lower urinary tract symptoms       Frequency, urgency, incompl...
Neurogenic bladder- causes
Renal Tumors   Renal Tumors       Renal adenomas: benign tumors located in renal        cortex       Renal cell carcino...
Renal Cell Carcinoma   Renal Cell Carcinoma       Clinical Manifestations            Hematuria            Flank Pain  ...
Wilms Tumor   Caused by genetic changes   500 cases/yr in U.S.   Age 1-5   MOST COMMON solid tumor in children   Diag...
Bladder Tumors   Bladder Tumors       Risks          Tobacco          Occupational exposure to chemical, rubber, texti...
Urinary Tract Infections   UTI       Risk Factors          Age          Sexually active females          Pregnancies ...
UTIs   Cystitis       Inflammation of the bladder       Most common bacteria          E Coli: outpatient          Kle...
UTIs   Pyelonephritis       Pathology:            Enlargement, scattered areas of abscess, increased             neutro...
UTIs   Laboratory diagnosis:       Urine          Greater than 5-10 WBC’S          Positive leukocyte esterase: enzyme...
UTIs in Children   Clinical Manifestations:       Infants: fever, vomiting, diarrhea, jaundice       Young children: ca...
UTIs in Children   Vesicourethral Reflux       Retrograde flow of infected urine into ureter        and kidney with perp...
Vesicoureteral Reflux
Glomerular Disorders   Glomerulonephritis - nephritic       Inflammation of the glomerulus       Etiology:          Im...
Glomerular Injury Mechanisms
Glomerulonephritis   Pathophysiology       With damage to the glomerulus there is swelling,        increased permeabilit...
Glomerulonephritis   Clinical Manifestations:       Hematuria       Proteinuria exceeding 3-5 g/day       Red blood ce...
Glomerulonephritis   Types       Post streptococcal          Can follow either pharyngitis or skin infections         ...
Glomerulonephritis   Types       IgA nephropathy         Occurs usually 24-48 hours after upper respiratory          or...
Glomerulonephritis   Types:       RPGN (Goodpasture Syndrome)         Antibody formation against both pulmonary        ...
Nephrotic Syndrome   Definition: excretion of 3.5 gm/day of protein   Pathology:       Excretion of large amount of pro...
Nephrotic Syndrome   Pathology (cont.)       Normally 25-hydroxycholecalciferol is carried        attached to globulin, ...
Nephrotic Syndrome
Renal Failure   Acute renal failure (AKI)       Oliguria of less than 30ml per hour or 400 ml/24        hours       Typ...
Renal Failure   Pre-renal failure: (-) renal blood flow.       Etiology: problem is outside of the kidney and        is ...
Renal Failure   Acute Renal Failure       Pathology          Decreased renal blood flow will decrease           glomeru...
Renal Failure   Acute renal failure       Intra-renal failure            Etiology:                 Acute tubular necro...
Renal Failure   Acute Renal Failure       Acute Tubular Necrosis            Ischemic etiology                 Most com...
Renal Failure   Acute Tubular Necrosis        Tubular obstruction: oliguria is partially caused by         ischemic edem...
Renal Failure   Acute Tubular Necrosis      Diagnostic criteria          Urine output less than 400 ml per 24 hours    ...
Renal Failure   Acute renal failure       Post renal acute renal failure          The etiology is obstruction of urine ...
Renal Failure   Acute Renal Failure       Clinical Manifestations            Phases                 Oliguria:         ...
(acute) Renal Failure
Oliguria Mechanisms in AKI
Chronic Renal Failure   Chronic renal failure is the irreversible loss    of renal function that affects nearly all    or...
Renal Failure   Chronic Renal Failure       Creatinine and Urea Clearance          Creatinine is released from the musc...
Renal Failure   Chronic Renal Failure       Creatinine and Urea Clearance          Tubular secretion occurs but there i...
Plasma Creatinine & GFR
Renal Failure   Chronic Renal Failure       Sodium and Water Balance         Increased sodium delivered to the tubules ...
Renal Failure   Chronic renal failure       Potassium         Control mediated by distal tubule excretion in          r...
Renal Failure   Chronic Renal Failure       Acid Base Balance          Hydrogen ions are secreted from the renal tubule...
Renal Failure   Phosphate and Calcium Balance       Renal failure produces decreased phosphate        excretion, decreas...
Renal Failure   Chronic Renal Failure       Ca and Phosphate Balance         Decreasing GFR will gradually overcome PTH...
Renal Failure   Hematocrit       Normocytic normochromic anemia secondary to        decreased levels of erythropoetin   ...
Renal Failure   Chronic Renal Failure       Proteins          Muscle protein decreases          Decreased levels of al...
Clinical Presentation of Renal            Failure
          Tests of Renal Function    Clearance and glomerular filtration rate       Inulin            Inconvenient    ...
   Urinalysis Tests               of Renal Function       Urine color            Light yellow, clear       Urine pH   ...
Tests of Renal Function   Urinalysis       Reagent strips (dipsticks)          Glucose          Bilirubin          Ur...
Aging and Renal Function   Decrease in kidney size   Decrease in renal blood flow and GFR   Number of nephrons decrease...
The End   Questions?       Thanks
Renal s2010
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Renal s2010

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  • podocyte - visceral epithelium with foot processes. --> filtration slits\nSandwich basement membrane to capillary endothelium. \n
  • Renal corpuscle - glomerulus inside Bowman’s capsule. \nMacula densa, part of the distance convoluted apparatus. \nJG cells find: hypoxemia, prostaglandins, sympathetic nervous system, \nMacula densa, sense salt. If low, will stimulate JG cells to secrete renin. \n
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  • Efferent arteriol -- only arteriol btwn capillary beds. \n
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  • Get renal ultrasound so that I can know if they have hydronephrosis.\n
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  • dysplastic transistional cells\n
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  • This is why we treat strep throat. \nNephritic - I for inflamation or immune: Sediment has hematurea, casts (RBC and WBC).\nNephrotic - O for open, protein leaks out. \n
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  • azotemia - elevated BUN and Cr, due to decrease in GFR. \nProduced by variety of disease processes. \nUremia - azotemia associated iwth other symptoms: heart, neuro, etc. \n“Constellateions of symptoms and signs with Azotemia”\n
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  • Pre-renal - system working hard, but working. \n
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  • Loss of renal mass in Cortes of kidney.\nGFR down by 50%.\n
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  • Renal s2010

    1. 1. Renal A&P and PathophysiologyReference: Pathophysiology text by Kathryn McCance Mindy Milton, PA-C, MPA
    2. 2. FUNCTIONS Homeostasis of the internal environment Maintain fluid and electrolyte balance Secretion of erythropoetin, renin, and dihydroxy Vitamin D
    3. 3. Anatomy Paired organs found within the retro- peritoneal space Parts:  Cortex  Medulla Supporting connective tissue  Renal capsule: covers outer surface  Adipose capsule: adipose tissue that surrounds capsule  Renal Fascia: dense fibrous structure that anchors kidney to surrounding structures
    4. 4. Anatomy
    5. 5. ANATOMY NEPHRON  Functional unit of the kidney  Three types:  Superficial cortical  Midcortical  Juxtamedullary nephrons - junction of cortex and medula, loop goes deepest into the medulla -->urine concentration.  Parts  Glomerulus: filtration membrane  Epithelial membrane:outer layer contain specialized cells called podocytes important in filtration  Basement membrane: middle layer  Endothelial membrane: inner layer perforated by fenestrations
    6. 6. Anatomy Glomerulus  Afferent arteriole: blood enters the glomerulus  Efferent arteriole: blood leaves the glomerulus  Blood pressure forces fluid out of the glomerulus into the capsule  Specialized cells known as juxtaglomerular cells located around the afferent arteriole.  Between the afferent and efferent arteriole is an area of the distal tubule called the macula densa  Forms the juxtaglomerular apparatus
    7. 7. Nephron
    8. 8. Anatomy: Glomerulus
    9. 9. Glomerulus
    10. 10. Glomerular Membrane: Podocytes
    11. 11. ANATOMY Nephron  Parts  Bowman’s capsule  Proximal tubule  Loop of Henle  Distal convoluted tubule  Collecting Duct  Macula densa/ juxtaglomerular cells (apparatus)  Vasa Recta
    12. 12. Nephron
    13. 13. Blood Supply to the Kidney
    14. 14. ANATOMY BLOOD SUPPLY  Vasa Recta  Network of capillaries that descend around the lower portion of the medullary loop of Henle  Only blood supply to the medulla  Influence osmolar concentration of the medullary extracellular fluid necessary for a concentrate urine  All capillaries drain into the venous system
    15. 15. Cortical Nephron
    16. 16. Medullary Nephron
    17. 17. Nephron blood vessels
    18. 18. Renal Blood Flow Glomerular arterioles  Receives blood from interlobular arteries  High pressure system  Arterial side of the nephron  Perfusion of 1200 ml per minute (20-25% of CO) Peritubular capillaries:  Low pressure system  Porous walls that allow for rapid reabsorption  Differing structures for cortical and medullary nephrons  Empties into the inferior vena cava
    19. 19. Autoregulation Mechanisms that maintain renal blood flow at constant pressure between 80-180 mm Hg Afferent arterioles have intrinsic ability to control glomerular blood flow and filtration rate GFR will stay relatively constant Changes in arteriolar pressure and afferent arteriolar resistance occurs in the same direction Constancy of solute and water excretion
    20. 20. Autoregulation Example  If systemic blood pressure increases, there will be vasoconstriction of the afferent arteriole to maintain filtration pressure  If systemic blood pressure decreases, vasodilation of the afferent arteriole to maintain filtration pressure  Control mechanisms  Myogenic response: Changes in stretch  Decrease arterial pressure = afferent arteriole relaxes ↑
  Increase arteriolar pressure = afferent arteriole contracts ↓
  Tubuloglomerular feedback: macula densa recognize changes in flow rate and NaCl levels  Increased NaCl = ↓
 
 
 
 
  
 
 
↑
 
 
 
 

    21. 21. Control of Renal Blood Flow Neural Mechanisms  Kidneys are innervated by the sympathetic nervous system  Stimulation of the sympathetic nervous system  Decrease in systemic BP = arteriole vasoconstriction = decrease in RBF and GFR  local autoregulatory mechanisms dampen the response Hormonal Control  Renin/angiotensin system  Atrial Naturietic peptide: increased right atrial pressure=decreased renin=decreased aldosterone=decreased renal reabsorption of NA and water=decreased blood volume
    22. 22. GLOMERULAR NET FILTRATION Pressures favoring  Pressures opposing filtration filtration  Glomerular capillary  Bowman’s capsule hydrostatic pressure hydrostatic pressure  Driving pressure that  Arterial end 10mmHg supports GFR  Venous end 10 mmHg  47mm Hg  Glomerular capillary  Bowman’s capsule colloid osmotic pressure colloid osmotic pressure  Arterial end 25 mm Hg  Venous end 35 mm Hg
    23. 23. Filtration Pressures
    24. 24. GLOMERULAR FILTRATION Filtration Pressure:  Net pressure forcing fluid out of the glomerulus Factors that affect filtration  Changes in hydrostatic pressure  Changes in the diameter of the afferent or efferent arterioles  Large molecules like plasma proteins cannot move through small pores in glomerular membrane  Negative charge along the filtration membrane impedes filtration of negatively charged particles as they repel
    25. 25. Juxtaglomerular Apparatus Juxtaglomerular cells:  Specialized cells located around the afferent arteriole where it enters to renal corpuscle Macula densa:  Portion of the distal tubule located between the afferent and efferent arteriole. Functions:  Control renal blood flow, GFR, and secretion of renin
    26. 26. Reabsorption/Secretion Tubular reabsorption: movement of fluid and solutes from the tubule to the peritubular capillaries  Active Transport  Diffusion Tubular secretion: secretion of substances from the peritubular capillaries to the tubular lumen
    27. 27. The Regulation of GFR
    28. 28. PROXIMAL TUBULE FUNCTIONS:  Reabsorption of electrolytes, water, and non electrolytes such as amino acids, glucose, and urea  Acid base balance: reabsorption of Na  Little actual change in osmotic balance  Isotonic  Secretes creatinine, drug end products
    29. 29. LOOP OF HENLE Function:  Primary function is the establish a hyperosmotic state within the medullary interstitial fluid  Occurs secondary to the reabsorption of more solute than water into the medullary interstitium  Fluid in the descending limb increases solute concentration  Fluid leaving the ascending limb is more dilute than when it entered
    30. 30. Nephron Functions
    31. 31. Loop of Henle ActivityWater NA/CLOut of Out ofD Limb A Limb
    32. 32. COUNTER CURRENT Hyperosmolarity of the interstitial fluid of the medullary of the kidney allows for the presence of a concentration gradient that provides for reabsorption of water in the presence of ADH Increased osmolarity of the loop and the vasa recta deep in the medulla prevents washing out of the medullary concentration gradient
    33. 33. Concentration of Urine
    34. 34. DISTAL TUBULE Final regulator of water balance Reabsorption of Na, H2O (ADH), HCO3 Secretion of K, Urea, H, drugs
    35. 35. Functions of ADH
    36. 36. Functions of ADH
    37. 37. Overall Renal Function
    38. 38. Renal Hormones Vitamin D  Diet and UV interaction of cholesterol in skin  Activation of hydroxylation starts in the liver, then KIDNEY  PTH stimulates hydroxylation  Vit D necessary for GI absorption and renal tubule reabsorption of calcium and inorganic phosphate
    39. 39. Renal Hormones (cont.) Erythropoietin  Produced in KIDNEY and stimulates RBC production in the bone marrow  Decrease Oxygen to kidney -> increase Epo  Afferent arteriole hypoxemia Renin  Produced in KIDNEY and increases plasma water and solute volume  Hypovolemia; Hypotension; Low sodium, and Beta 1 adrenergic stimulation -> increase Renin
    40. 40. Anatomy: Ureters Muscular tubes that extend from kidney to bladder Lie retroperitoneal and attached to posterior abdominal wall Enter posterior wall of urinary bladder Small slit like openings to prevent backflow of urine from bladder to ureter Three layers  Inner epithelial layer  Middle muscular layer  Outer connective tissue layer Peristaltic contractions move urine to bladder
    41. 41. Radiographic View of the Urinary System
    42. 42. Anatomy: Urinary Bladder Hollow muscular organ that acts as storage reservoir for urine Mucosa lining has rugae that disappear as bladder distends Triangular area bounded by the ureteral openings and the entrance to the urethra is called the trigone Urethral entrance lies at the apex of the trigone which is the most inferior aspect of the urinary bladder Innervated by the post ganglionic fibers of the parasympathetic nervous system
    43. 43. Anatomy of the Bladder
    44. 44. Micturition Reflex Stretch receptors are stimulated as the bladder fills with urine Urge to urinate at approximately 200 ml of urine Relaxation of the external and internal sphincters Gradual increase in volume will repetitively stimulate the reflex until emptying of the bladder occurs Infants do not have voluntary control over urination because they do not have the corticospinal connections established
    45. 45. Pathophysiology Finally … Renal  Systemic disease  Intrinsic Urinary  Infection  Obstruction
    46. 46. Obstructive Uropathy Consequences of obstruction  Hydroureter: obstruction of the ureter with accumulation of urine  Hydronephrosis: retrograde increases in hydrostatic pressure in the renal pelvis and calyces can increase accumulation of urine in the renal collecting system.  Complete obstruction: decreased glomerular filtration and resulting renal failure  Partial obstruction: chronically can cause compression, accumulation of urine, ischemic damage and atrophy with decreased concentrating ability of the kidney.
    47. 47. Sites of Urinary Obstruction
    48. 48. Nephrolithiasis Kidney Stones: Nephrolithiasis  Types:  Calcium oxylate - alkaline urine  Struvite - staghorn calcui.  Uric acids - acidic urine.  Pathophysiology:  High urinary concentration of stone forming substances  Changes in pH and temperature  Drugs and diet  Decreased urinary flow  Grow in the renal papilla or pelvis
    49. 49. Nephrolithiasis Calcium stones  Smallest  Increased frequency in middle age men  80% idiopathic  Can be associated with increased levels of calcium secondary to prolonged immobilization or hyperparathyroidism Uric Acid  Caused by gout with increased uric acid production, and hyperuricosuria. Enhanced by concentrated and acidic urine.
    50. 50. Nephrolithiasis Kidney Stones  Clinical manifestations:  Pain, Pain, Pain - can have radiating pain to labia/ scrotum, or disurea.  Diagnostic  BUN, Cr - is this stone causing a reduction in renal function.  KUB (Flat plate of the abdomen)  CT scan  IVP (Intravenous Pyelogram)
    51. 51. Lower urinary tract obstruction Prostate enlargement Urethral stricture Severe pelvic organ prolapse (cystocele) Neurogenic bladder dyssynergia
    52. 52. Neurogenic Bladder Dysfunctional filling or emptying Lower urinary tract symptoms  Frequency, urgency, incomplete empty, nocturia, incontinence, etc… Neurological lesions of brain, spinal cord or peripheral system cause
    53. 53. Neurogenic bladder- causes
    54. 54. Renal Tumors Renal Tumors  Renal adenomas: benign tumors located in renal cortex  Renal cell carcinoma: increased in men with 60% survival rate at 5 years  Risks  Tobacco, Obesity, analgesic use  Type: adenocarcinomas
    55. 55. Renal Cell Carcinoma Renal Cell Carcinoma  Clinical Manifestations  Hematuria  Flank Pain  Flank mass  Fatigue  Weight Loss  Anemia  Elevated alkaline phosphatase, LFT’S  Diagnosis: renal ultrasound, CT scan, IVP, and renal angiogram
    56. 56. Wilms Tumor Caused by genetic changes 500 cases/yr in U.S. Age 1-5 MOST COMMON solid tumor in children Diagnosed by parents noticing abd mass Treatment improved if Dx early DO your ABD Exam during WCC
    57. 57. Bladder Tumors Bladder Tumors  Risks  Tobacco  Occupational exposure to chemical, rubber, textile industries  Know relationship to mutations in the tumor suppressor p 53 gene  Clinical manifestations  Hematuria  Progression associated with pelvic pain or increased frequency of urination
    58. 58. Urinary Tract Infections UTI  Risk Factors  Age  Sexually active females  Pregnancies  Antibiotic use  Catheters  Medical diseases: diabetes, neurogenic bladder
    59. 59. UTIs Cystitis  Inflammation of the bladder  Most common bacteria  E Coli: outpatient  Klebsiella Structural Changes  Proteus Instrumentation  Staphylococcus Nosocomial  Clinical Manifestations  Dysuria, frequency urgency, turbid urine  Suprapubic discomfort, bleeding secondary to involvement of superficial epithelial cells of bladder
    60. 60. UTIs Pyelonephritis  Pathology:  Enlargement, scattered areas of abscess, increased neutrophils in the tubules.  Chronic infection: caliceal dilatation and cortical scarring, interstitial edema, lymphocytic involvement, increased casts in the tubular proper.  Clinical Manifestations  Fever, chills, flank pain, hematuria, generalized malaise  Some research has shown that about 30% of patients with lower tract manifestations have upper tract disease as well.
    61. 61. UTIs Laboratory diagnosis:  Urine  Greater than 5-10 WBC’S  Positive leukocyte esterase: enzymes found primarily in neutrophilic granules.  WBC casts: reflective of upper tract disease  Markedly elevated protein suggestive of glomerular disease not basic infection  Hematuria or occult blood  Urine culture with greater than 100,000 colonies of individual bacteria
    62. 62. UTIs in Children Clinical Manifestations:  Infants: fever, vomiting, diarrhea, jaundice  Young children: can have dysuria, frequency, bed wetting or incontinence in previously dry child.  Increased incidence of structural abnormalities  More rapid follow up for vesicoureteral reflux to prevent renal scarring from chronic pyelonephritis
    63. 63. UTIs in Children Vesicourethral Reflux  Retrograde flow of infected urine into ureter and kidney with perpetuation of infection and resultant scarring of kidney cortex  Increased presence in children  Diagnosed by voiding cystourethrogram and occasionally IVP.  Structural changed evaluated by renal ultrasound  Graded 1-5 See page 1412
    64. 64. Vesicoureteral Reflux
    65. 65. Glomerular Disorders Glomerulonephritis - nephritic  Inflammation of the glomerulus  Etiology:  Immunologic mechanisms: post streptococcal damage  Drugs and toxins  Vascular diseases  Pathophysiology  Glomerulus is the high pressure filtration component of the normal kidney tubule  Normally does not allow passage of large
    66. 66. Glomerular Injury Mechanisms
    67. 67. Glomerulonephritis Pathophysiology  With damage to the glomerulus there is swelling, increased permeability, and decreased effectiveness of cell junctions  Large proteins molecules and red blood cells are filtered and are seen in the urine  Swelling of the glomerulus will increase pressure, decrease glomerular filtration, and can have a secondary effect of causing systemic edema and hypertension
    68. 68. Glomerulonephritis Clinical Manifestations:  Hematuria  Proteinuria exceeding 3-5 g/day  Red blood cell casts  HTN  Edema  Oliguria  Smoky colored urine  Generalized malaise, low grade fever, back pain
    69. 69. Glomerulonephritis Types  Post streptococcal  Can follow either pharyngitis or skin infections  Clinical Manifestations usually occur within ten days after pharyngitis and two to three weeks after a skin infection  Elevated anti-streptolysin O levels, history of pharyngitis, hematuria, proteinuria, red blood cell casts
    70. 70. Glomerulonephritis Types  IgA nephropathy  Occurs usually 24-48 hours after upper respiratory or gastrointestinal infection  Abnormal glycosylated IgA becomes trapped in the glomerular membrane and increased proliferation of the membrane secondary to the effect of growth factors  Initial manifestations is usually hematuria, with decreased presentation with edema, proteinuria, or HTN
    71. 71. Glomerulonephritis Types:  RPGN (Goodpasture Syndrome)  Antibody formation against both pulmonary capillary and glomerular membranes  Characterized by pulmonary hemorrhage and rapidly progressing glomerular disease  Rapid decline in glomerular function, HTN, edema, renal insufficiency  Most common young men 20-30 years of age
    72. 72. Nephrotic Syndrome Definition: excretion of 3.5 gm/day of protein Pathology:  Excretion of large amount of protein leads to hypoalbuminemia, decreased colloid osmotic pressure, edema.  Stimulation of adaptive responses secondary to third spacing of fluids with elevated ADH, aldosterone, and decreased responsiveness of the kidney to atrial naturietic hormone. All lead to retention of sodium and water.  Hyperlipidemia secondary to increased synthesis by the liver, decreased catabolism, and increased delivery of lipid precursors to the liver
    73. 73. Nephrotic Syndrome Pathology (cont.)  Normally 25-hydroxycholecalciferol is carried attached to globulin, if lost in the urine there will be decreased calcium absorption in the gut with hypocalcemia  Decreased calcium will cause secondary hyperparathyroidism and osteomalacia
    74. 74. Nephrotic Syndrome
    75. 75. Renal Failure Acute renal failure (AKI)  Oliguria of less than 30ml per hour or 400 ml/24 hours  Types  Pre-renal failure  Intra-renal failure  Post-renal failure
    76. 76. Renal Failure Pre-renal failure: (-) renal blood flow.  Etiology: problem is outside of the kidney and is related to decreased renal blood flow  Hypotension, hypovolemia, inadequate cardiac output (CHF).  Trauma with blood loss; vomiting and diarrhea with volume loss; dehydration secondary to overuse of diuretics; third spacing of fluid with relative volume depletion that can occur in liver failure
    77. 77. Renal Failure Acute Renal Failure  Pathology  Decreased renal blood flow will decrease glomerular filtration. Decreased urine output.  Diagnostic criteria:  Elevated specific gravity (kidney able to function normally so it will try to conserve fluid in the presence of decreased flow)  Urine sodium less than 10mEq (kidney function normal so it will conserve sodium in the presence of decreased flow)  BUN/Cr ratio is greater than 15:1 (BUN will elevate greater than Cr due to decreased glomerular filtration with normal tubular function
    78. 78. Renal Failure Acute renal failure  Intra-renal failure  Etiology:  Acute tubular necrosis: nephrotoxic or ischemic  Glomerulonephritis  Vascular disease  Intertstitial nephritis  Acute Tubular Necrosis - most common.  Nephrotoxic: drugs like aminoglycosides, heavy metal poisoning, radiocontrast media.
    79. 79. Renal Failure Acute Renal Failure  Acute Tubular Necrosis  Ischemic etiology  Most common post trauma, surgery, blood loss with decreased renal blood flow and ischemic of the tubules.  Patchy loss of function to tubules with decreased tubular function  Oliguria with urine output of less than 400 ml per 24 hours
    80. 80. Renal Failure Acute Tubular Necrosis  Tubular obstruction: oliguria is partially caused by ischemic edema, sloughing of tubular cells and products of inflammation causing obstruction of urine flow  Changes in permeability with increased tubular reabsorption  Regional hypoxia may cause increase in the release of angiotensin and decreased renal blood flow
    81. 81. Renal Failure Acute Tubular Necrosis  Diagnostic criteria  Urine output less than 400 ml per 24 hours  Specific gravity of urine is low (in this case even though the kidney has a decreased flow pattern and the normal adaptive response would be to retain water, the kidney tubule is damaged and concentrating ability is reduced)  Urine sodium greater than 30mEq (again the kidney tubule should be retaining sodium in the presence of decreased flow, but the tubule is abnormal secondary to the damage and continues to waste sodium.  BUN/Cr ratio less than 15:1: Generally higher elevations of serum Cr as the tubule normally secretes Cr; abnormal function of the tubule means decreased excretion
    82. 82. Renal Failure Acute renal failure  Post renal acute renal failure  The etiology is obstruction of urine flow outside of the kidney proper  Often can be caused by prostate enlargement, bladder outlet obstruction  Obstruction of urine flow will cause increasing backup of urine flow and pressure within the kidneys bilaterally, with anuria initially
    83. 83. Renal Failure Acute Renal Failure  Clinical Manifestations  Phases  Oliguria:  Less than 30 ml urine output per hour  Associated elevation of BUN and CR  Edema, CHF(Cardiac), N/V, fatigue, hyperkalemia, fluid retention  Diuretic phase  Increased urine output with poor reabsorption in the tubules can lead to decreased NA, K, dehydration Acute Tubular Necrosis  Recovery phase  Can lasts up to 6-12 months
    84. 84. (acute) Renal Failure
    85. 85. Oliguria Mechanisms in AKI
    86. 86. Chronic Renal Failure Chronic renal failure is the irreversible loss of renal function that affects nearly all organ systems Progression  Reduced renal reserve  Renal insufficiency  Renal failure  End-stage renal disease
    87. 87. Renal Failure Chronic Renal Failure  Creatinine and Urea Clearance  Creatinine is released from the muscle and excreted by the kidney  Excreted by glomerular filtration and secretion  Amount produced equals amount excreted
    88. 88. Renal Failure Chronic Renal Failure  Creatinine and Urea Clearance  Tubular secretion occurs but there is little adaptive ability to increase secretion in the presence of increased serum levels  Decreased GFR will cause increased Cr  BUN both filtered and reabsorbed and excreted primarily by Glomerular filtration
    89. 89. Plasma Creatinine & GFR
    90. 90. Renal Failure Chronic Renal Failure  Sodium and Water Balance  Increased sodium delivered to the tubules in chronic renal failure  Need to increase the excretion in order to maintain serum levels within narrow range  Tubule will decrease Reabsorption and increase excretion  Increased problem with reabsorbing sodium with decreased GFR to 25%: increased loss
    91. 91. Renal Failure Chronic renal failure  Potassium  Control mediated by distal tubule excretion in response to aldosterone  Initially decreased renal function can be controlled at normal intake levels with increased tubular secretion and increased loss through the bowel  As kidney function decreases total body K increases and can be a factor in the decision to start dialysis
    92. 92. Renal Failure Chronic Renal Failure  Acid Base Balance  Hydrogen ions are secreted from the renal tubules and excreted in the urine in combination with phosphate and ammonia buffers  Early stages pH maintained by increased acid secretion and bicarbonate reabsorption  Later stages decreased adaptive ability with increased metabolic acidosis
    93. 93. Renal Failure Phosphate and Calcium Balance  Renal failure produces decreased phosphate excretion, decreased renal formation of 1,25- (OH)2 Vitamin D, and hypocalcemia  Elevated plasma phosphate levels binds Ca causing hypocalcemia and stimulation of Parathyroid Hormone  PTH increases release of CA from bone and increased phosphate excretion
    94. 94. Renal Failure Chronic Renal Failure  Ca and Phosphate Balance  Decreasing GFR will gradually overcome PTH’s ability to control serum phosphate levels  Hyperphosphatemia, hypocalcemia, and increased PTH will increase bone dissolution and be responsible for the development of osteomalacia  Impaired synthesis of activated Vitamin D in the kidney will also reduce intestinal absorption of CA and enhance the problem
    95. 95. Renal Failure Hematocrit  Normocytic normochromic anemia secondary to decreased levels of erythropoetin  There can also be decreased RBC life span and bleeding that can add to the anemia Hypertriglyceridemia  Accelerated atherosclerosis, decrease lipoprotein lipase within the capillary and decrease hepatic lipase all decrease the breakdown, add to atherosclerosis
    96. 96. Renal Failure Chronic Renal Failure  Proteins  Muscle protein decreases  Decreased levels of albumin. complement, and transferrin  Proteinuria occurs with increased risk for kidney damage  Carbohydrates  Glucose intolerance secondary to insulin resistance
    97. 97. Clinical Presentation of Renal Failure
    98. 98.  Tests of Renal Function Clearance and glomerular filtration rate  Inulin  Inconvenient  Creatinine  Clinical choice 24 hr urine volume and serum creatinine level  Cockcroft-Gault formula  GFR = (140 - age) x wt (kg)__ (x.85 if female) 72 x serum creatinine Blood tests  Plasma creatinine concentration  Normal 0.7-1.2 mg/dl  50% GFR reduction = Cr 2x normal value  Best for monitoring CRF progression  Blood urea nitrogen (BUN)  Normal range 10-20 mg/dl  Varied by diet and hydration
    99. 99.  Urinalysis Tests of Renal Function  Urine color  Light yellow, clear  Urine pH  4.5 – 8.0  Specific gravity  1.016-1.022  Correlates with osmolality  Acidic or alkaline urine effects results  Urine sediment  RBCs  Casts  WBC, RBC, Epithelial  Crystals  Normal or pathologic  WBCs  Infection
    100. 100. Tests of Renal Function Urinalysis  Reagent strips (dipsticks)  Glucose  Bilirubin  Urobilinogen  Leukocyte esterase  Nitrites - infection  Ketones  Proteins  RBCs, hemoglobin, and myoglobin
    101. 101. Aging and Renal Function Decrease in kidney size Decrease in renal blood flow and GFR Number of nephrons decrease due to renal vascular and perfusion changes Glomerular capillaries atrophy Tubular transport response decreases Increased bladder symptoms  Urgency, frequency, and nocturia
    102. 102. The End Questions?  Thanks

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