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Flashcards in First Aid Imported Deck (240):
1

Course of ureters

Ureters pass UNDER the uterine artery and UNDER the ductus deferens "Water under the bridge" (Ureters [water] pass under bridge [artery/ductus deferens])

2

Total Body Weight (TBW) (divide it up by water distribution)

TBWeight: 40% nonwater, 60% water
TBWater: 1/3 extracellullar fluid, 2/3 intracellular fluid
TBWater - ECF = ICF
ECF: 1/4 plasma volume, 3/4 interstitial volume

3

Ions in ECF vs. ICF

ECF: high NaCl, high HCO3-, low K+ (salty ocean outside cells)
ICF: High K+, high Mg2+, low NaCl, anions: proteins, organic phosphates (HIKIN' - HIgh K+ INside)

4

Measuring plasma, ECF volume

Plasma volume is measured w/ radiolabeled albumin. ECF volume is measured by inulin.

5

Plasma osmolarity

Normal is about 290 mOsm

6

Renal Clearance Equation (For Cx, or the volume of plasma from which the substance is completely cleared per unit time)

For substance x: Cx = (Ux V) / Px
Where: Ux = urine concentration of x Px = plasma concentration of x V = urine flow rate

7

Values for clearance (Cx) vs. GFR

Cx > GFR: net tubular secretion of x
Cx < GFR: net tubular reabsorption of x
Cx = GFR: no net secretion or reabsorption

8

Glomerular filtration barrier

Responsible for filtration of plasma according to size and net charge
Composition:
1.) Fenestrated capillary endothelium (size barrier)
2.) Fused basement membrane w/ heparan sulfate (negative charge barrier)
3.) Epithelial layer consisting of podocyte foot processes

9

Lost in nephrotic syndrome

The charge barrier. Result: albuminemia, hypoproteinemia, generalized edema, and hyperlipidemia.

10

What substance is used to calculate GFR (ideally)?

Inulin can be used b/c it is freely filtered and is neither reabsorbed nor secreted.
So: GFR = (U-inulin V) / P-inulin = C-inulin =Kf [(Pgc - Pbs) - (πgc - πbs)] gc = glomerular capillary bs = Bowman's space (πbs normally = 0)

11

What substance is used to approximate GFR?

Creatinine clearance is used as an approximate measure of GFR. It slightly overestimates GFR b/c creatinine is moderately secreted by the renal tubules

12

Effectice Renal Plasma Flow (ERPF)

Can be estimated using PAH clearance b/c it is both filtered and actively secreted in the proximal tubule. All PAH entering the kidney is excreted.

13

Calculating ERPF

Use PAH
ERPF = (U-PAH V) / P-PAH = C-PAH

14

Calculating Renal Blood Flow (RBF)

RBF = RPF / (1 - Hct) Can use ERPF for RPF, but remember that ERPF underestimates true RPF by about 10%.

15

Filtration Fraction (how do you calculate it?)

GFR / RPF

16

Filtered Load

GFR x Plasma Concentration

17

Effect of NSAIDs, ACE-I's on GFR and RPF (mechanism)

18

Effect of afferent arteriole constriction

RPF: decreased
GFR: decreased
FF: No change

19

Effect of Efferent Arteriole Constriction

RPF: Decreased
GFR: Increased
FF: Increased

20

Effect (on renal fxn) of increased plasma protein concentration

RPF: No change
GFR: decreased
FF: decreased

21

Effect (on renal fxn) of decreased plasma protein concentration

RPF: no change
GFR: increased
FF: increased

22

Effect of constriction of ureter (on renal fxn)

RPF: No change
GFR: decreased
FF: decreased

23

Free Water Clearance

Ability to dilute urine. Given urine flow rate, urine osmolarity, and plasma osmolarity, be able to calculate free water clearance:
C-H2O = V - C-osm (V is urine flow rate; C-osm = (U-osm V) / P-osm)

24

Effect of ADH on free water clearance (C-H2O)

with ADH: C-H2O > 0 (retention of water) w/o ADH: C-H2O < 0 (exretion of free water) *isotonic urine: Isotonic urine: C-H2O = 0 (seen w/ loop diuretics)

25

Glucose Clearance (renal)

Glucose at normal plasma level is completely reabsorbed in proximal tubule. At plasma glucose of 200 mg/dL , glucosuria begins threshold ). At 350 mg/dL , transport mechanism is saturated Tm ).
*glucosuria is an important clinical clue to DM

26

Amino Acid clearance (renal)

Reabsorption by at least 3 distinct carrier systems, w/ competitive inhibition w/in each group. Secondary active transport occurs in PT and is saturable.

27

Early PCT

Early PCT: contains brush border. Reabsorbs all glucose and AAs, and most bicarbonate, Na+, and water. Isotonic absorption. Secretes ammonia, which acts as a buffer for secreted H+. PTH: inhibits Na+/phosphate cotransport --< phosphate excretion ATII: stimulates Na+/H+ exchange --< increased Na+ and water reabsorption (can lead to contraction alkalosis)

28

Thin Descending loop of Henle

Passively reabsorbs water via medullary hypertonicity (impermeable to sodium). Makes urine hypertonic.

29

Thick ascending LOH

Actively reabsorbs Na+, K+, and Cl-.
Indiretly induces paracellular reabsorption of Mg2+ and Ca2+.
Impermeable to water.
Diluting segment.
Makes urine hypotonic.

30

Early distal convoluted tubule

Actively reabsorbs Na+, Cl-
Makes urine hypotonic
PTH: increases Na+/Ca2+ exchange, leading to Ca2+ reabsorption

31

Distal Convoluted Tubule

Collecting tubules: reabsorb Na+ in exchange for secreting K+ and H+ (regulated by aldosterone) Aldosterone: leads to insertion of Na+ channels on luminal side. ADH - acts at V2 receptors, inserting aquaporin H2O channels on luminal side

32

TF/P <1

Solute is reabsorbed more slowly than water. There is net secretion of solute.

33

Solute is reabsorbed more slowly than water. There is net secretion of solute.

TF/P <1

34

TF/P = 1

Solute and water are reabsorbed at the same rate. Solute is neither reabsorbed nor secreted.

35

Solute and water are reabsorbed at the same rate. Solute is neither reabsorbed nor secreted.

TF/P = 1

36

TF/P > 1

Solute is reabsorbed more quickly than water.

37

Solute is reabsorbed more quickly than water.

TF/P > 1

38

Tubular creatinine and inulin

Increase in concentration (but not amount) along the proximal tubule, due to water reabsorption.

39

Cl- vs. Na+ along tubule

Cl- is absorbed distal to where Na+ is reabsorbed, so its relative concentration increases.

40

Na+ along tubule

Reabsorption drives H2O reabsorption, so it nearly matches osm

41

Reabsorption drives H2O reabsorption, so it nearly matches osm

Na+ along tubule

42

Angiotensin II (ATII) Effects on bp/HR regulation

Affects baroreceptor function Limits reflex bradycardia, which would normally accompany its pressor effects

43

Affects baroreceptor function Limits reflex bradycardia, which would normally accompany its pressor effects

Angiotensin II (ATII) Effects on bp/HR regulation

44

ANP

Released from atria in response to increased volume May act as a "check" on RAAS: decreases renin and increases GFR

45

Released from atria in response to increased volume May act as a "check" on RAAS: decreases renin and increases GFR

ANP

46

ADH regulates...

Primarily regulates osmolarity (In low-volume states, both ADH and aldosterone act to protect blood volume)

47

Primarily regulates osmolarity (In low-volume states, both ADH and aldosterone act to protect blood volume)

ADH regulates...

48

Aldosterone regulates...

Primarily regulates blood volume (In low-volume states, both ADH and aldosterone act to protect blood volume)

49

Primarily regulates blood volume (In low-volume states, both ADH and aldosterone act to protect blood volume)

Aldosterone regulates...

50

Angiotensin --< Angiotensin I

Angiotensin (from liver) is converted to Angiotensin I by renin (from the kidney). Renin production is upregulated by high BP (sensed @ JG cells) and sympathetic tone; it is downregulated by Na+ delivery (sensed @ MD cells)

51

Angiotensin I --< Angiotensin II

Converted by Angiotensin Converting Enzyme (ACE) - produced in lungs ACE inhibits bradykinin

52

AT-II on systemic vasculature

Acts on AT-II receptors on smooth muscle to increase BP

53

AT-II on glomerulus

Constricts efferent arteriole --< increases FF to preserve renal fxn in low-volume states (i.e. w/ low RBF)

54

AT-II on adrenal gland

Stimulates adrenal gland to produce aldosterone --< aldosterone causes increased Na+ channel, Na+/K+ pump insertion in principal cells --

55

AT-II on posterior pituitary

Stimulates posterior pituitary to produce ADH. --< ADH increases H2O channel insertion in principal cells --< This causes water reabsorption

56

AT-II on proximal tubule

Increases PT Na+/H+ activity --< This leads to H2O reabsorption (Can also lead to contraction alkalosis)

57

AT-II on hypothalamus

Causes thirst

58

Causes thirst

AT-II on hypothalamus

59

Juxtaglomerular Apparatus (JGA)

JG cells (modified smooth muscle of affert arteriole) and Macula Densa (Na+ sensor, part of the DCT) *This structure defends glomerular filtration rate via renin-angiotensin aldosterone system (RAAS)*

60

JG cells (modified smooth muscle of affert arteriole) and Macula Densa (Na+ sensor, part of the DCT) *This structure defends glomerular filtration rate via renin-angiotensin aldosterone system (RAAS)*

Juxtaglomerular Apparatus (JGA)

61

Function of JG Cells

Secrete renin (leading to increased angiotensin II and aldosterone levels) in response to decreased renal bp, decreased Na+ delivery to distal tubule, and increased sympathetic tone.

62

Secrete renin (leading to increased angiotensin II and aldosterone levels) in response to decreased renal bp, decreased Na+ delivery to distal tubule, and increased sympathetic tone.

Function of JG Cells

63

NSAIDs and renal failure

Can cause acute renal failure by inhibiting the renal production of prostaglandins, which keep the afferent arterioles vasodilated to maintain GFR.

64

EPO

Produced by endothelial cells of peritubular capillaries in response to hypoxia

65

Produced by endothelial cells of peritubular capillaries in response to hypoxia

EPO

66

Proximal Tubule Cells' endocrine function

Convert 25-OH Vitamin D to 1,25-(OH)2 Vitamin D This increases intestinal absorption of both Ca2+ and phosphate.

67

Convert 25-OH Vitamin D to 1,25-(OH)2 Vitamin D This increases intestinal absorption of both Ca2+ and phosphate.

Proximal Tubule Cells' endocrine function

68

PTH effect on Kidney (Direct, Indirect)

Acts directly on kidney to increase renal Ca2+ reabsorption. However, also acts indirectly, stimulating PT cells to make 1,25-(OH)2-VitD, which increases intestinal absorption of both Ca2+ and phosphate.

69

Acts directly on kidney to increase renal Ca2+ reabsorption. However, also acts indirectly, stimulating PT cells to make 1,25-(OH)2-VitD, which increases intestinal absorption of both Ca2+ and phosphate.

PTH effect on Kidney (Direct, Indirect)

70

JG cells' endocrine function

secrete renin in response to decreased renal arterial pressure and increased renal sympathetic discharge (beta-1 effect)

71

secrete renin in response to decreased renal arterial pressure and increased renal sympathetic discharge (beta-1 effect)

JG cells' endocrine function

72

Prostaglandins and GFR

PG's are secreted to vasodilate the afferent arterioles, in order to increase GFR.

73

Atrial Natriuretic Peptide's (ANP's) effect on kidney

Secreted in response to increased atrial pressure. Causes increased GFR and increased Na+ filtration w/ no compensatory Na+ reabsorption in the distal nephron to lower volume. Net effect: Na+ loss and volume loss.

74

PTH's effect on kidney

Secreted in response to low plasma [Ca2+]. Causes increased [Ca2+] reabsoption in DCT, decreased phosphate reabsorption in PCT (i.e., increased excretion of phosphate), and 1,25(OH)2-VitD production (which leads to increased Ca2+ and phosphate absorption from gut)

75

ATII's effect on kidney

Synthesized in response to low bp. Causes efferent arteriole constriction to increase GFR and FF, but with a compensatory Na+ reabsorption in the distal nephron . Net effect: preservation of renal fxn in low-volume state (increased FF) w/o additional volume loss (distal Na+ reabsorption).

76

ADH (Vasopressin) effect on kidney

Secreted in response to high plasma osmolarity and low blood volume. Binds to receptors on principal cells , causing increased number of water channels and increased H2O reabsorption.

77

Aldosterone's effect on kidney

Secreted in response to low blood volume (via ATII) and increased plasma [K+] Causes increased Na+ reabsorption, increased indirect K+ secretion, and increased H+ secretion

78

Metabolic Acidosis

pH: Decreased PCO2: Decreased [HCO3-]: Decreased (*primary disturbance) Compensatory response: Hyperventilation

79

pH: Decreased PCO2: Decreased [HCO3-]: Decreased (*primary disturbance) Compensatory response: Hyperventilation

Metabolic Acidosis

80

Metabolic Alkalosis

pH: Increased PCO2: Increased [HCO3-]: Increased (*primary disturbance) Compensatory response: Hypoventilation

81

pH: Increased PCO2: Increased [HCO3-]: Increased (*primary disturbance) Compensatory response: Hypoventilation

Metabolic Alkalosis

82

Respiratory Acidosis

pH: decreased PCO2: Increased (*primary disturbance) [HCO3-]: Increased Compensatory response: Increased renal [HCO3-] reabsorption

83

pH: decreased PCO2: Increased (*primary disturbance) [HCO3-]: Increased Compensatory response: Increased renal [HCO3-] reabsorption

Respiratory Acidosis

84

Respiratory Alkalosis

pH: increased PCO2: decreased (*primary disturbance) [HCO3-]: decreased Compensatory response: decreased [HCO3-] reabsorption

85

pH: increased PCO2: decreased (*primary disturbance) [HCO3-]: decreased Compensatory response: decreased [HCO3-] reabsorption

Respiratory Alkalosis

86

Henderson-Hasselbalch Equation (for renal Acid-Base physiology)

pH = pKa + log ( [HCO3-] / 0.03PCO2)

87

Winter's Formula

Respiratory compensation in response to metabolic acidosis can be quantified w/ this formula: PCO2 = 1.5(HCO3-) + 8 +/-2 (gives you an "expected" value for PCO2 --< use this to tell if the respiratory response is adequate.)

88

Acidemia (pH >7.4) w/ PCO2 < 40mmHg (Respiratory Acidosis) Ddx

Hypoventilation: Airway obstruction Acute Lung dz Chronic lung dz Opioids, narcotics, sedatives Weakening of respiratory muscles

89

Acidemia (pH > 7.4) w/ PCO2 > 40 mmHg (Metabolic Acidosis w/ compensation - Hyperventilation) 1st step in Ddx

Check anion gap: Anion gap = Na+ - (Cl- + HCO3-) Normal = 8-12 mEq/L

90

Metabolic Acidosis w/ compensation (hyperventilation), elevated anion gap (< 12 mEq/L)

MUDPILES Methanol (formic acid) Uremia Diabetic ketoacidosis Paraldehyde or Phenformin Iron tablets or INH Lactic acidosis Ethylene glycol (oxalic acid) Salicylates

91

Metabolic Acidosis w/ compensation (hyperventilation), normal anion gap (8-12 mEq/L)

Diarrhea Glue sniffing Renal tubular acidosis Hyperchloremia

92

Alkalemia (pH 40mmHg Ddx

Respiratory Alkalosis: Hyperventilation (e.g. early high-altitude exposure) Aspirin ingestion (early)

93

Alkalemia (pH < 7.4) w/ PCO2 < 40 mmHg Ddx

Metabolic alkalosis w/ compensation (hypoventilation): Diuretic use Vomiting Antacid use Hyperaldosteronism

94

Renal tubular acidosis type 1

Defect in H+/K+ ATPase of the collecting tubules: inability to secrete H+. This can lead to hypokalemia.

95

Defect in H+/K+ ATPase of the collecting tubules: inability to secrete H+.

This can lead to hypokalemia. Renal tubular acidosis type 1

96

Renal Tubular Acidosis Type 2

Defect in PT HCO3- reabsorption. Can lead to hypokalemia.

97

Defect in PT HCO3- reabsorption. Can lead to hypokalemia.

Renal Tubular Acidosis Type 2

98

Renal tubular acidosis Type 3

Hypoaldosteronism --< hyper kalemia --< inhibition of ammonia excretion in the PT. This leads to decreased urine pH due to decreased buffering capacity.

99

Hypoaldosteronism --< hyper kalemia --< inhibition of ammonia excretion in the PT. This leads to decreased urine pH due to decreased buffering capacity.

Renal tubular acidosis Type 3

100

Acid-Base Nomogram

101

Plotting on an acid-base nomogram

102

RBC casts

Indicate glomerular inflammation (nephritic syndromes), ischemia, or malignant HTN *Presence of casts indicates that hematuria/pyuria is of renal origin*

103

WBC casts What do they indicate?

Indicate tubuloinsterstitial dz, acute pyelonephritis, glomerular D/O's. *Presence of casts indicates that hematuria/pyuria is of renal origin*

104

Granular ("muddy brown") casts

Acute tubular necrosis *Presence of casts indicates hematuria/pyuria is of renal origin*

105

Hyaline casts

Nonspecific *Presence of casts indicates that hematuria/pyuria is of renal origin*

106

Nephritic syndrome (What is it?)

An Inflammatory process involving the glomeruli, leading to hematuria, azotemia, RBC casts in urine, oliguria, HTN, and proteinuria (>3.5g/day)

107

Urine findings: Bladder cancer

RBC's, no casts

108

Urine findings: acute cystitis

WBC's, no casts

109

Acute Poststreptococcal Glomerulonephritis

LM: Glomeruli enlarged and hypercellular, PMN's, "lumpy-bumpy" appearance. EM: Subepithelial immune complex (IC) humps. IF: Granular Most frequently seen in children. Peripheral and periorbital edema. Resolves spontaneously.

110

Rapidly progressive (crescentic) glomerulonephritis

(A nephritic syndrome) LM and IF - Crescent-moon shape. Poor prognosis. May result in 3 patterns: Goodpasture's syndrome, Wegener's granulomatosis, Microscopic polyarteritis

111

(A nephritic syndrome) LM and IF - Crescent-moon shape. Poor prognosis. May result in 3 patterns: Goodpasture's syndrome, Wegener's granulomatosis, Microscopic polyarteritis

Rapidly progressive (crescentic) glomerulonephritis

112

Goodpasture syndrome

(A nephritic syndrome) A type of rapidly progressive (crescentic) glomerulonephritis Type II hypersensitivity: antibodies to GBM (linear IF) Male-dominant dz. Heaturia/hemoptysis (lung involvement).

113

(A nephritic syndrome) A type of rapidly progressive (crescentic) glomerulonephritis Type II hypersensitivity: antibodies to GBM (linear IF) Male-dominant dz. Heaturia/hemoptysis (lung involvement).

Goodpasture syndrome

114

Wegener's Granulomatosis

(A nephritic syndrome) A type of rapidly progressive (crescentic) glomerulonephritis c-ANCA (classical anti-neutrophil cytoplasmic Abs)

115

(A nephritic syndrome) A type of rapidly progressive (crescentic) glomerulonephritis c-ANCA (classical anti-neutrophil cytoplasmic Abs)

Wegener's Granulomatosis

116

Microscopic polyarteritis

(A nephritic syndrome) A type of rapidly progressive (crescentic) glomerulonephritis p-ANCA (perinuclear anti-neutrophil cytoplasmic Abs)

117

(A nephritic syndrome) A type of rapidly progressive (crescentic) glomerulonephritis p-ANCA (perinuclear anti-neutrophil cytoplasmic Abs)

Microscopic polyarteritis

118

Diffuse proliferative glomerulonephritis (due to SLE)

(A nephritic syndrome) Subendothelial DNA-antiDNA ICs --< "wire looping" of capillaries. [bright red staining of the GBM of peripheral capillary loops ("wire loop" lesion) on the right half of the glomerulus (3 o'clock)] Granular IF. Most common cause of death in SLE. SLE can present as nephrotic syndrome.

119

(A nephritic syndrome) Subendothelial DNA-antiDNA ICs --

Diffuse proliferative glomerulonephritis (due to SLE)

120

Berger's Disease (IgA Glomerulonephropathy)

(A nephritic syndrome) Increased synthesis of IgA. Immunocomplexes deposit in mesangium. Often follows URI; often presents as nephrotic syndrome.

121

(A nephritic syndrome) Increased synthesis of IgA. Immunocomplexes deposit in mesangium. Often follows URI; often presents as nephrotic syndrome.

Berger's Disease (IgA Glomerulonephropathy)

122

Alport's syndrome

(A nephritic syndrome) Mutation in type IV collagen --< split basment membrane Nerve D/O's, ocular D/O's, deafness

123

(A nephritic syndrome) Mutation in type IV collagen --< split basment membrane Nerve D/O's, ocular D/O's, deafness

Alport's syndrome

124

Nephrotic syndrome Protein loss? Associated Sx?

presents w/ massive proteinuria (<3.5g/day), frothy urine, hyperlipidemia, edema.

125

presents w/ massive proteinuria (<3.5g/day), frothy urine, hyperlipidemia, edema.

Nephrotic syndrome Protein loss? Associated Sx?

126

Membranous glomerulonephritis (diffuse membranous glomerulopathy)

(a nephrotic syndrome) LM - diffuse capillary and GBM thickening EM - "spike and dome" appearance IF - granular SLE's nephrotic presentation. Caused by drugs, infxns, SLE. Most common cause of adult nephrotic syndrome.

127

(a nephrotic syndrome) LM - diffuse capillary and GBM thickening EM - "spike and dome" appearance IF - granular SLE's nephrotic presentation. Caused by drugs, infxns, SLE. Most common cause of adult nephrotic syndrome.

Membranous glomerulonephritis (diffuse membranous glomerulopathy)

128

Minimal change disease (Lipoid nephrosis)

(a nephrotic syndrome) LM - normal glomeruli EM - Foot process effacement Often postinfectious. Most common in children. Responds to corticosteroids.

129

(a nephrotic syndrome) LM - normal glomeruli EM - Foot process effacement Often postinfectious. Most common in children. Responds to corticosteroids.

Minimal change disease (Lipoid nephrosis)

130

Amyloidosis

(A nephrotic syndrome) LM - congo red stain, apple-green birefringence Associated w/ multiple myeloma, chronic conditions, TB, rheumatoid arthitis.

131

(A nephrotic syndrome)

LM - congo red stain, apple-green birefringence Associated w/ multiple myeloma, chronic conditions, TB, rheumatoid arthitis. Amyloidosis

132

Diabetic glomerulopathy

(a nephrotic syndrome) Nonenzymatic glycosylation (NEG) of GBM leads to increased permeability, thickinening. NEG of efferent arterioles increases GFR, leading to mesangial damage, wire looping. LM: Kimmelstiel-Wilson "wire loop" lesions.

133

(a nephrotic syndrome) Nonenzymatic glycosylation (NEG) of GBM leads to increased permeability, thickinening. NEG of efferent arterioles increases GFR, leading to mesangial damage, wire looping. LM: Kimmelstiel-Wilson "wire loop" lesions.

Diabetic glomerulopathy

134

Focal segmental glomerulosclerosis

(A nephrotic syndrome) LM - segmental sclerosis and hyalinosis Most common glomerular dz in HIV pts. More severe in HIV pts.

135

(A nephrotic syndrome) LM - segmental sclerosis and hyalinosis Most common glomerular dz in HIV pts. More severe in HIV pts.

Focal segmental glomerulosclerosis

136

Membrano-proliferative glomerulonephritis

(A nephrotic syndrome) Subendothelial immune complexes w/ granular IF. EM - "tram-track" appearance due to GBM splitting caused by mesangial ingrowth. Can present as nephritic syndrome. Usually progresses slowly to CRF. Associated w/ HBV < HCV.

137

(A nephrotic syndrome) Subendothelial immune complexes w/ granular IF. EM - "tram-track" appearance due to GBM splitting caused by mesangial ingrowth.

Can present as nephritic syndrome. Usually progresses slowly to CRF. Associated w/ HBV < HCV. Membrano-proliferative glomerulonephritis

138

Glomerular Histology (Normal)

(normal is on the left side) EP = Epithelium w/ foot processes US = Urinary space GBM = Glomerular Basement Membrane EN = Fenestrated Endothelium MC = Mesangial Cells EM = Extracellular Matrix

139

Glomerular histopathology

[Below on right] 1 = subepithelial deposits (membranous nephropathy) 2 = Large irregular subepithelial deposits or "humps" (acute glomerulonephritis) 3 = Subendothelial deposits (lupus glomerulonephritis) 4 = Mesangial deposits (IgA nephropathy) 5 = Ab binding to GBM: smooth linear pattern on IF (Goodpasture's) 6 = Effacement of epithelial foot processes (common in all forms of glomerular injury w/ proteinuria)

140

Kidney stones Lead to? Major types?

Can lead to complications like hydronephrosis and pyelonephritis. 4 major types: 1. Calcium 2. Ammonium 3. Uric Acid 4. Cystine

141

Calcium Kidney stones

Most common kidney stones (75-80%). Calcium oxalate (below), calcium phosphate (not shown), or both. Conditions that cause hypercalcemia (cancer, elevated PTH, high VitD, milk-alkali syndrome) can lead to hypercalciuria and stones. Tend to recur. Radiopaque. Oxalate crystals can result from ethylene glycol (antifreeze) or vitamin C abuse.

142

Ammonium Magnesium Phosphate (struvite) kidney stones

2nd most common kidney stone. Caused by infxn w/ urease-positive bugs (Proteus vulgaris, Staphylococcus, Klebsiella ). Can form staghorn calculi that can be a nidus for UTIs. [calcium oxalate staghorn calculus shown below] Radiopaque or radiolucent. Worsened by alkaluria.

143

Uric Acid kidney stones

Strong association w/ hyperuricemia (e.g. gout) Often seen as a result of diseases w/ increased cell turnover, such as leukemia and myeloproliferative D/O's. radiolU cent

144

Cystine kidney stones

Most often secondary to cystinuria. Hexagonal shape. Rarely, may form cystine staghorn calculi. Faintly radiopaque. Tx w/ alkalinization of urine.

145

Renal Cell Carcinoma Epidemiology

Most common renal malignancy Most common in men ages 50-70 Increased incidence w/ smoking and obesity

146

Most common renal malignancy Most common in men ages 50-70 Increased incidence w/ smoking and obesity

Renal Cell Carcinoma Epidemiology

147

Genetics of Renal Cell Carcinoma (RCC)

Associated w/ von Hippel-Lindau and gene deletion in Chromosome 3.

148

Associated w/ von Hippel-Lindau and gene deletion in Chromosome 3.

Genetics of Renal Cell Carcinoma (RCC)

149

Renal cell carcinoma (disease)

Invades IVC and spreads hematogenously. Manifests clinically w/: hematuria, palpable mass, secondary polycythemia, flank pain, fever, and weight loss. Originates in renal tubule cells --< polygonal clear cells. Gross appearance:

150

Invades IVC and spreads hematogenously. Manifests clinically w/: hematuria, palpable mass, secondary polycythemia, flank pain, fever, and weight loss. Originates in renal tubule cells --

Gross appearance: Renal cell carcinoma (disease)

151

Associated w/ RCC

paraneoplastic syndromes (ectopic EPO, ACTH, PTHrP, and prolactin)

152

paraneoplastic syndromes (ectopic EPO, ACTH, PTHrP, and prolactin)

Associated w/ RCC

153

Wilm's tumor

Most common renal malignancy of early childhood (ages 2-4). Presents w/ huge, palpable flank mass, hemihypertrophy. Contains embryonic glomerular structures.

154

Most common renal malignancy of early childhood (ages 2-4). Presents w/ huge, palpable flank mass, hemihypertrophy.

Contains embryonic glomerular structures. Wilm's tumor

155

Wilm's tumor (genetic basis)

Deletion of tumor suppressor gene WT1 on chromosome 11.

156

Deletion of tumor suppressor gene WT1 on chromosome 11.

Wilm's tumor (genetic basis)

157

WAGR complex

W ilm's tumor A niridia (absent iris) G enitourinary malformation mental-motor R etardation (Can occur together as a complex)

158

Transitional Cell Carcinoma

Most common tumor of urinary tract system (can occur in renal calyces, renal pelvis, ureters, and bladder). Painless hematuria is suggestive of bladder cancer. Associated problems in your P ee SAC : Phenacetin Smoking Aniline dyes Cyclophosphamide

159

Acute Pyelonephritis

Affects cortex w/ relative sparing of glomeruli/vessels. White cell casts in urine are pathognomonic. Presents with fever, CVA tenderness.

160

Chronic Pyelonephritis

Coarse, asymmetric corticomedullary scarring, blunted calyx. Tubules contain eosinophilic casts (thyroidization of the kidney).

161

Diffuse cortical necrosis

Acute generalized infarction of cortices of both kidneys. Likely due to a combination of vasospasm and DIC. Associated w/ obstetric catastrophes (e.g. abruptio placentae) and septic shock

162

Acute generalized infarction of cortices of both kidneys. Likely due to a combination of vasospasm and DIC. Associated w/ obstetric catastrophes (e.g. abruptio placentae) and septic shock

Diffuse cortical necrosis

163

Drug-induced interstitial necrosis

Acute interstitial renal inflammation. Fever, rash, eosinophilia, hematuria 2 wks after administration. Drugs (e.g. penicillin derivatives, NSAIDs, diuretics) act as haptens, inducing hypersensitivity

164

Acute tubular necrosis (ATN)

Loss of cell polarity, epithelial cell detachment, necrosis, granular ("muddy brown") casts. Most common cause of ARF in hospital. Reversible, but fatal if left untreated (Tx w/ dialysis). Associated w/ renal ischemia (e.g. shock, sepsis), crush injury (myoglobulinuria), toxins. Death most often occurs during initial oliguric phase. Recovery in 2-3 wks.

165

Stages of ATN

3 stages: 1.) Inciting event 2.) Maintenance (low urine) 3.) Recovery

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Renal Papillary necrosis

Sloughing of renal papillae, leading to gross hematuria, proteinuria. Associated w/: 1.) DM 2.) Acute pyelonephritis 3.) Chronic phenacetin use (acetaminophen is a phenacetin derivative) 4.) Sickle cell anemia

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Acute Renal Failure (ARF)

In a normal nephron, BUN is reabsorbed (for countercurrent multiplication), but creatinine is not. ARF is defined as an abrupt decline in renal function w/ increased creatinine and increased BUN over a period of several days Can be: pre-renal, intrinsic renal, or post-renal

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Pre-renal azotemia (ARF)

Decreased RBF (e.g. hypotension) causing decreased GFR. Na+/H2O and urea are retained by kidney, so BUN/creatinine ratio increases in an attempt to conserve volume.

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Intrinsic renal ARF

Generally due to ATN or ischemia/toxins. Patchy necrosis leads to debris obstructing tubule and fluid backflow across necrotic tubule, decreasing GFR. Urine has epithelial/granular casts. BUN reabsorption is impaired --< decreased BUN/creatinine ratio.

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Urine osmolarity in different types of ARF

Pre-renal: 350 in either one

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Urine [Na+] in different types of ARF

Pre-renal: >10% Intrinsic renal: <40%

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Fe-Na+ (fractional excretion of sodium) in different types of ARF

Pre-renal: >1% Intrinsic renal: <4%

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Serum BUN/Cre ratio in different types of ARF

Pre-renal: 15 Post-renal: <15

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Consequences of renal failure

Inability to make urine and excrete nitrogenous waste --< uremia (clinical syndrome marked by increased BUN and creatinine and associated symptoms). Consequences: 1.) Anemia (failure of EPO production) 2.) Renal osteodystrophy (failure of active VitD production) 3.) Hyperkalemia, which can lead to cardiac arrhythmias 4.) Metabolic acidosis due to decreased acid secretion and decreased generation of HCO3- 5.) Uremic encephalopathy 6.) Sodium and H2O excess --< CHF and pulmonary edema 7.) Chronic pyelonephritis 8.) HTN 9.) Pericarditis

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Fanconi's Syndrome

Decreased PT transport of AA's, glucose, phosphate, uric acid, protein, and electrolytes. Can be congenital or acquired. Causes include: Wilson's dz, glycogen storage dz's, and drugs (e.g. cisplatin, expired TCN).

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Decreased PT transport of AA's, glucose, phosphate, uric acid, protein, and electrolytes. Can be congenital or acquired. Causes include: Wilson's dz, glycogen storage dz's, and drugs (e.g. cisplatin, expired TCN).

Fanconi's Syndrome

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Defects associated w/ Fanconi's syndrome

Decreased phosphate reabsorption --< Rickets Decreased HCO3- reabsorption --< Metabolic acidosis Decreased early Na+ reabsorption --< increased Na+ reapsorption --< hypokalemia

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Autosomal Dominant Polycystic Kidney Dz = ADPKD (formerly adult polycystic kidney dz)

Multiple, large, bilateral cysts that ultimately destroy the parenchyma. Enlarged kidneys. Presents w/ flank pain, hematuria, HTN, urinary infxn, progressive renal failure. Autosomal Dominant mutation in APKD2 . Death from urema or HTN (due to increased renin production). Associated w/ polycystic liver dz, berry aneurysms (due to HTN), and mitral valve prolapse.

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Autosomal Recessive Polycystic Kidney Dz = ARPKD (Formerly infantile polycystic kidney dz)

Infantile presentation in parenchyma. Autosomal recessive. Associated w/ hepatic cysts and fibrosis.

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Dialysis cysts

Cortical and medullary cysts resulting from long-standing dialysis.

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Medullary cystic dz

Medullary cysts. Ultrasound shows small kidney. Poor prognosis.

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Medullary sponge dz

Collecting duct cysts. Good prognosis.

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Electrolyte disturbances: Na+

Low: Disorientation, stupor, coma High: Neurologic - irritability, delirium, coma

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Low: Disorientation, stupor, coma High: Neurologic - irritability, delirium, coma

Na+

185

Electrolyte disturbances: Cl-

Low: secondary to metabolic alkalosis, hypokalemia, hypovolemia, increased aldosterone High: secondary to non-anion gap acidosis

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Low: secondary to metabolic alkalosis, hypokalemia, hypovolemia, increased aldosterone High: secondary to non-anion gap acidosis

Cl-

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Electrolyte disturbances: K+

Low: U-waves on ECG, flattened T-waves, arrhythmias, paralysis High: Peaked T-waves, wide QRS, arrhythmias

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Low: U-waves on ECG, flattened T-waves, arrhythmias, paralysis High: Peaked T-waves, wide QRS, arrhythmias

K+

189

Electrolyte disturbances: Ca2+

Low: tetany, neuromuscular irritability High: Delirium, renal stones, abdominal pain, not necessarily calciuria

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Low: tetany, neuromuscular irritability High: Delirium, renal stones, abdominal pain, not necessarily calciuria

Ca2+

191

Electrolyte disturbances: Mg2+

Low: Neuromuscular irritability, arrhythmias High: Delirium, decreased DTRs, cardiopulmonary arrest

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Low: Neuromuscular irritability, arrhythmias High: Delirium, decreased DTRs, cardiopulmonary arrest

Mg2+

193

Electrolyte disturbances: Phosphate

Low: low-mineral ion product causes bone loss, osteomalacia High: High-mineral ion product causes renal stones, metastatic calcifications

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Low: low-mineral ion product causes bone loss, osteomalacia High: High-mineral ion product causes renal stones, metastatic calcifications

Phosphate

195

Mannitol (mechanism)

Osmotic diuretic. Increasaes tubular fluid osmolarity, producing increased urine flow. [#2 below/right - continues to work in thin descending LOH, collecting duct as well]

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Osmotic diuretic. Increasaes tubular fluid osmolarity, producing increased urine flow. [#2 below/right - continues to work in thin descending LOH, collecting duct as well]

Mannitol

197

Mannitol (clinical use)

Shock, drug overdose, decreased intracranial/intraocular pressure

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Shock, drug overdose, decreased intracranial/intraocular pressure

Mannitol

199

Mannitol (toxicity)

Pulmonary edema, dehydration. Contraindicated in anuria, CHF.

200

Acetazolamide (mechanism)

Carbonic anhydrase inhibitor. Causes self-limited NaHCO3 diuresis and reduction in total-body HCO3- stores. [#1 below/right]

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Carbonic anhydrase inhibitor. Causes self-limited NaHCO3 diuresis and reduction in total-body HCO3- stores. [#1 below/right]

Acetazolamide

202

Acetazolamide (clinical use)

Glaucoma, urinary alkalinization, metabolic alkalosis, altitude sickness.

203

Glaucoma, urinary alkalinization, metabolic alkalosis, altitude sickness.

Acetazolamide

204

Acetazolamide (toxicity)

Hyperchloremic metabolicacidosis ("ACIDazolamide causes ACIDosis") neuropathy NH3 toxicity sulfa allergy.

205

Furosemide (mechanism)

Sulfonamide loop diuretic. Inhibits cotransport system (Na+, K+, 2Cl-) of thick ascending limb of LOH. Abolishes hypertonicity of medulla, preventing concentration of urine. Increased Ca2+ excretion ("Lo ops Lo se calcium")

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Sulfonamide loop diuretic. Inhibits cotransport system (Na+, K+, 2Cl-) of thick ascending limb of LOH. Abolishes hypertonicity of medulla, preventing concentration of urine. Increased Ca2+ excretion ("Lo ops Lo se calcium")

Furosemide

207

Furosemide (clinical use)

Edematous states (CHF, cirrhosis, nephrotic syndrome, pulmonary edema) HTN Hypercalcemia

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Edematous states (CHF, cirrhosis, nephrotic syndrome, pulmonary edema) HTN Hypercalcemia

Furosemide

209

Furosemide (toxicity)

"OH DANG!" Ototoxicity Hypokalemia Dehydration Allergy (sulfa) Nephritis (interstitial) Gout

210

Ethacrynic Acid (mechanism)

Phenoxyacetic acid derivative (NOT a sulfonamide), but essentially same action as furosemide.

211

Phenoxyacetic acid derivative (NOT a sulfonamide), but essentially same action as furosemide.

Ethacrynic Acid

212

Ethacrynic Acid (clinical use)

Diuresis in pts allergic to sulfa drugs.

213

Diuresis in pts allergic to sulfa drugs.

Ethacrynic Acid

214

Ethacrynic acid (toxicity)

Similar to furosemide ("OH DANG!"), but can be used in hyperuricemia, acute gout (never used to treat gout)

215

Hydrochlorothiazide (HCTZ) (mechanism)

Thiazide diuretic. Inhibits NaCl reabsorption in early distal tubule, reducing diluting capacity of nephron. Decreases Ca2+ excretion.

216

Thiazide diuretic. Inhibits NaCl reabsorption in early distal tubule, reducing diluting capacity of nephron.

Decreases Ca2+ excretion. Hydrochlorothiazide (HCTZ)

217

Hydrochlorothiazide (HCTZ) (clinical use)

HTN CHF Idiopathic hypercalciuria Nephrogenic diabetes insipidus

218

HTN CHF Idiopathic hypercalciuria Nephrogenic diabetes insipidus

Hydrochlorothiazide (HCTZ)

219

Hydrochlorothiazide (HCTZ) (toxicity)

Hypokalemic metabolic acidosis Hyponatremia HyperG lycemia, hyperL ipidemia, hyperU ricemia, and hyperC alcemia ("Hyper-GLUC") Sulfa allergy.

220

K+-sparing diuretics

S pironolactone, T riamterene, A miloride, eplerenone (the K+ STAys)

221

K+-sparing diuretics (mechanism)

Spironolactone is a competitive aldosterone receptor antagonist in the cortical collecting tubule. Triamterene and amiloride act at the same part of the tubule by blocking Na+ channels in the CCT

222

Spironolactone is a competitive aldosterone receptor antagonist in the cortical collecting tubule. Triamterene and amiloride act at the same part of the tubule by blocking Na+ channels in the CCT

K+-sparing diuretics

223

K+-sparing diuretics (clinical use)

Hyperaldosteronism K+ depletion CHF

224

Hyperaldosteronism K+ depletion CHF

K+-sparing diuretics

225

K+-sparing diuretics (toxicity)

Hyperkalemia (can lead to arrhythmias) Endocrine effects w/ aldosterone antagonists (e.g. spironolactone causes gynecomastia, antiandrogen effects)

226

Urine NaCl w/ diuretics

Increases with all diuretics

227

Urine K+ w/ diuretics

Increases w/ all except K+-sparing diuretics

228

Blood pH and diuretics: decrease (acidemia)

Carbonic anhydrase inhibitors: decreasesd HCO3- reabsorption. K+-sparing: hyperkalemia leads to K+ entering all cells (via H+/K+ exchanger) in exchange for H+ exiting cells.

229

Blood pH and diuretics: increase (alkalinemia)

Loop diuretics and thiazides cause alkalemia through several mechanisms: 1.) Volume contraction --< increased ATII --< increased Na+/H+ exchange in PT --< increased HCO3- ("contraction alkalosis") 2.) K+ loss leads to K+ exiting all cells (via H+/K+ exchanger) in exchange for H+ entering cells 3.) In low K+ state, H+ (rather than K+) is exchanged for Na+ in principal cells, leading to alkalosis and "paradoxical aciduria"

230

Urine Ca2+ and diuretics

Increased by loop diuretics: abolish lumen-positive potential in thick ascending limb of LOH --< decreased paracellular Ca2+ reabsorption --< hypocalcemia, increased urinary Ca2+ Decreased in thiazides: Block luminal Na+/Cl- contransport in DCT --< increased Na+ gradient --< increased interstitial Na+/Ca2+ exchange --< hypercalcemia

231

ACE inhibitors

Captopril, enalapril, lisinopril ("___-pril") *Losartan is an AT-II receptor antagonist (ARB). It is not an ACE-I, and does not cause cough.

232

ACE Inhibitors (mechanism)

Inhibit angiotensin-converting enzyme, reducing levels of ATII and preventing inactivation of bradykinin, a potent vasodilator. Renin releases is increased due to loss of feedback inhibition.

233

Inhibit angiotensin-converting enzyme, reducing levels of ATII and preventing inactivation of bradykinin, a potent vasodilator. Renin releases is increased due to loss of feedback inhibition.

ACE Inhibitors

234

ACE-Inhibitors (clinical use)

HTN CHF Diabetic renal dz

235

HTN CHF Diabetic renal dz

ACE-Inhibitors

236

ACE-Inhibitors (toxicity)

"CAPTOPRIL" Cough Angioedema Proteinuria Taste changes hypOtension Pregnancy problems (fetal renal damage) Rash Increased renin Lower angiotensin II Also, hyperkalemia. *Avoid w/ bilateral renal artery stenosis b/c ACE-I's significantly reduce GFR by preventing constriction of effecrent arterioles*

237

Thyroglossal duct

Connects the thyroid to the tongue. It normally disappears, but may persist as the pyramidal lobe of the thyroid.

238

Thyroid diverticulum

arises from floor of primitive pharynx and descends into neck.

239

Most common ectopic site for thyroid tissue

tongue

240

Quick and dirty way to predict PCO2 from changes in HCO3- for metabolic alkalosis/acidosis

PCO2 increases by 0.7mmHg for every 1 mEq/L of HCO3- in metabolic alkalosis PCO2 decreases by 0.7-0.9mmHg for every 1 mEq/L of HCO3- in metabolic acidosis (Respiratory is different)