Test #2 Flashcards

(105 cards)

1
Q

Nephritic characteristics

A

hematuria

rbc and mixed cell casts

variable proteinuria

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2
Q

Nephrotic characteristics

A

Marked proteinuria (>3.5 g/day)

Lipiduria

Fatty casts

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3
Q

Nephritic causes

A

Post-infectious/proliferative glomerulonephritis

IgA neuropathy/vasculitis (HSP)

Lupus nephritis

Thin basement membrane disease

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4
Q

Nephrotic causes

A

Systemic disease

  • Diabetic neuropathy
  • Amyloidosis

Minimal change disease

Focal segmental glomerulosclerosis (FSGS)

Membranous neuropathy

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5
Q

Focal Nephritic Patterns

A

ex: IgA nephropathy

Inflammatory lesions in <1/2 glomeruli

UA: rbc, ~rbc casts, mild protein

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6
Q

Diffuse Nephritic Patterns

A

ex: post-strep glomerulonephritis (PSGN)

Affects > 1/2 glomeruli

UA: lots of protein, rbc and rbc casts

Edema, HTN, may have renal insufficiency

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7
Q

Nephrotic Patters

A

Affects many glomeruli

No inflammation/immune complex deposits

Edema, hyperlipidemia, hypoalbuminemia

Ex: Diabetic neuropathy

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8
Q

Poststreptococcal glomerular nephritis (PSGN)

A

Most common acute nephritic cause

1-3 weeks post strep/3-6 weeks post GABHS

MOA: Glomerular immune complex disease, viral/parasitic infection (rare)

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9
Q

Poststreptococcal glomerular nephritis symptoms and diagnosis

A

Often asx; discolored urine w/ sediment, edema, HTN

Hx of strep infection w/in 3-6 weeks

UA: gross hematuria, proteinuria

Streptozyme test: antistreptolysin

Biopsy only to r/o other glomerular dx, late presentations w/o clear strep history

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10
Q

Recurrent hematuria episodes indicate:

A

IgA nephropathy

Not PSGN

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11
Q

Poststreptococcal glomerular nephritis treatment

A

Supportive

Sodium and water restriction w/ loop diuretic (edema and HTN)

Dialysis w/ acute renal failure

Recovery begins w/in 1st 2 wks

Late renal complications are rare: HTN, proteinuria, renal insufficiency

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12
Q

IgA Neuropathy/Berger’s Disease

A

Most common primary GN cause

Rare in blacks; 80% 15-35 yo

MOA: Mesangial depositions of IgA complexes

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13
Q

IgA Nephropathy Presentation

A

1: Gross recurrent hematuria possibly after URI (synpharyngitic)
- flank pain and fever
2: Microscopic hematuria which may progress, mild proteinuria
3: Nephrotic syndrome: protein and lipid urea, fatty casts
- edema, renal insufficiency, HTN, hematuria

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14
Q

IgA Nephropathy diagnosis and treatment

A

Dx: kidney biopsy -> IgA deposits in mesangium

-Can also indicates cirrhosis, celiac disease, HIV

Tx: BP control (ACEI)

-Severe/progressive: Corticosteroids +/- immunosuppressants

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15
Q

Henoch-Scholein Purpura (HSP)/IgA vasculitis

A

Systemic vasculitis from IgA complex deposits in tissue

Most common vasculitis in children (3-15 years)

Generally mild in kids, worse in adults

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16
Q

Henoch-Scholein Purpura symptoms

A

Tetrad:

1: Palpable purpura w/o thrombocytopenia or coagulopathy
2: Arthritis or arthralgia
3: Abdominal pain
4: Renal disease (GN)

Develops over days-weeks, presentation order varies

Spectrum w/ kids to adults: Kids: mild hematuria +/-proteinuria, adults: severe nephrotic syndrome/renal failure

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17
Q

Henoch-Scholein Purpura diagnosis and treatment

A

Dx: kidney bx - only w/ uncertain dx or severe renal involvement - marked proteinuria/impaired renal function

Tx: Crescentic GN - pulse IV methylprednisone, then oral prednisone

Rare progression to ESRD -> dialysis and transplant

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18
Q

Rapidly progressive glomerulonephritis (RPGN)

A

Acute GN w/ rapid progression to ESRD

Morphological crescent formation w/in glomerular vessel wall

-fibrin formation w/ macrophage, T cells, cytokines in Bowman’s space

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19
Q

Types of RPGN

A

1: Anti-glomerular basement membrane (GBM/Goodpasture syndrome)
- anti-GBM abs in lungs and glomerulus
2: Immune complex RPGN - deposit in glomeruli
- IgA Nephropathy, PSGN, lupus nephritis
3: Pauci-immune RPGN - necrotizing GN and vasculitis
- ANCA positive, systemic vasculitis symptoms

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20
Q

RPGN symptoms

A

Insidious - fatigue and edema

Acute - macroscopic hematuria, oliguria, edema, renal insufficiency

GBM - pulmonary hemorrhage, hemoptysis, pulmonary infiltrates, dyspnea

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21
Q

RPGN Diagnosis and Treatment

A

UA: hematuria, rbc casts, proteinuria

Increase BUN/Creat, renal bx to confirm

Serologic assay for type

Tx: Pulse methylprednisolone, PO cyclophosphamide, consider plasmapheresis

-treatment gets more specific w/ bx results

Catch early to minimize irreversible injury

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22
Q

Dark granular and epithelial casts in urine indicate:

A

Pure acute tubular necrosis

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23
Q

Crystal particles in urine

A

Crystalluric acute renal failure

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24
Q

wbc and wbc casts in urine:

A

Acute interstitial nephritis

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25
rbc and rbc casts in urine:
Proliferative/necrotizing glomerulonephritis
26
Prerenal UNa, BUN/Creat, FENa
Urine Na: \<20 BUN/Creat: \>20:1 (\>20) FENa: \<1
27
Intrinsic UNa, BUN/Creat, FENa
Urine Na: \>20 BUN/Creat: \<10:1 (\<20) FENa: \>2
28
Postrenal UNa, BUN/Creat, FENa
Urine Na: variable BUN/Creat: 10-20:1 (\<20) FENa: variable
29
Acute Interstitial Nephritis
Renal lesion causes creatinine clearance decline Drugs most common cause - PCN, cephalosporin, sulfa, NSAIDs, Rifampin, Dilantin, Allopurinol Infections dx also cause: strep, leptospirosis, CMV, Histoplasmosis, Rocky Mountain Spotted Fever Immunologic causes: Lupus, Sjogren's Sarcoidosis, Cryoglobulinemia
30
Acute Interstitial Nephritis sx and tx
Sx: fever, hematuria, peripheral eosinophilia, rash -UA: rbc, +/- wbc/wbc casts, proteinuria (NSAIDS) Tx: Supportive, remove cause - 1-2 week high dose steroids if persistent - rare progression to ESRD
31
Proteinuria monitoring
Initial assessment w/ new HTN, DM, hematuria, decreased GFR Annual monitoring: Bx proven GN, reflux neuropathy, DM Routinely monitor pts on nephrotoxic agents
32
Common CKD microorganisms
Staphylococcus E. coli Klebsiella (hospitalized pts w/ pulmonary infections)
33
Endocarditis prophylaxis
2g Amoxicillin OR 600 mg Clindamycin 1 hour before dentist
34
Immunizations and Dialysis
Screen for Hep B and C before you start on dialysis/put on transplant list Influenza and Pneumococcus vaccine (revaccinate every 5 years)
35
CKD Medications to avoid
NSAIDs Metformin if SCr \>1.5 (men) 1.4 (women) Magnesium-containing meds (laxatives, antacids) Caution w/ Abx (PCN, cephalosporin, sulfa, fluroquinolones)
36
Renal Cell Carcinoma
Originates in renal cortex #1 renal cancer - men (60-80yo) Rick: smoking, HTN, obesity, acquired kidney cystic dx
37
Clear Cell Carcinoma
PCT - most common RCC, Chromosome 3P deletion Solid/less cystic, typically invades vasculature Microscopic: lipid and glycogen cytoplasm, bland cells w/ poor differentiation -forms solid nest, tubules w/ fine vasculature
38
Papillary Carcinoma (Chromophil)
PCT, trisomy 7, 16,17 Better prognosis than clear cell Microscopic: delicate vascular cores w/ overlying tumor cell layer -Psammoma bodies = necrosis/calcification @ tips
39
Chromophobe RCC
Cellular sheets darker than clear cell Arise in CD intercalated cells, lower progression risk than clear cell Microscopic: pink (eosinophilic) cell sheet w/ perinuclear halos
40
Collecting duct carcinoma (Bellini duct carcinoma)
Aggressive, affects young and Black Rare
41
Oncocytoma
Oncocytes - C-met oncogene mutation Well-differentiated, very eosinophilic granular cytoplasm CD intercalated cells Usually unilateral and single, mets are rare
42
RCC Clinical features
Triad: Flank pain, gross hematuria, palpable renal mass Nonspecific features: fever, fatigue, weight loss, scrotal varicocele, paraneoplastic syndrome Usually present late, asx early Dx: US then CT Refer cysts to urologist
43
RCC common metastasis sites
Lung Abdominal lymph nodes Bone CT w/ a suspicious X-ray, bone scan/PET scan to locate
44
RCC Treatment
Surgical removal - radical nephrectomy or -Partial if \<4 cm, unilateral tumor Radical = take everything to Gerota's fascia and adrenal, +/- part of IVC
45
RCC Staging
Stage 1: \<7cm, limited to kidney - 95% 5 year survival Stage 2: \>7cm, limited to kidney - 88% Stage 3: tumor in major vein/adrenal/Gerota's fascia/regional lymph node - 59% Stage 4: Tumor beyond Gerota's fascia or in \>1 regional lymph node - 20%
46
Wilm's Tumor (Nephroblastoma)
Most common renal tumor in kids Abnormal renal development - metanephric blastoma proliferation w/o tubular or glomerular differentiation Risk: aniridia (iris), hemihypertrophy, undescended testes, hypospadias (ureter)
47
Wilm's Tumor symptoms and diagnosis
Sx: palpable mass, abdominal pain, HTN, hematuria, rarely bilateral Dx: US and contrast CT, excision/bx for definitive diagnosis
48
Wilms Tumor staging
Stage 1: unilateral, completely removable Stage 2: cancer is beyond the kidney, but still completely removable Stage 3: cancer is contained to abdomen, cannot remove completely Stage 4: mets to lungs/liver/bone/brain Stage 5: cancer in both kidneys (bilateral tumors are rare)
49
Wilms Tumor treatment and appearance
Chemo for all Radical nephrectomy for stages 1-4, get as much out as possible Stage 5 - radical nephrectomy, pt must be on transplant list Large, single, well-circumscribed tumor -less hemorrhage than RCC, can have cyst formation
50
Benign renal tumors
Renal papillary adenoma - Cortical tubules, trisomy 7 and 17 Renal fibroma/Hamartoma - small, benign fibrous nodule in renal pyramids Angiomyolipoma - blood vessels, muscle, and fat =\> occur w/ tuberou sclerosis, easy to spot on radiograph Can't distinguish benign from malignant until excised and biopsied
51
Transitional Cell Carcinoma (TCC)
Transitional epithelium in urinary tract - calyces to uretal orifice Smoking, male, 60-70 yo, black Sx: hematuria, renal colic, hydronephrosis w/u: urine cytology, cystoscopy, IVP Tx: radical nephroureterectomy and chemo
52
Renal Sarcoma
Rare, mesenchymal cell tumor Grow fast and big, peak incidence ~5th decade Sx: abdominal pain, palpable mass, gross hematuria Dx: CT Tx: surgical excision
53
Renal abscess
Hematogenous or UTI origin with obstruction Enterococcus (E. coli) or staph Sx: fever, chill.s abdominal pain, weight loss, hematuria -looks like acute pyelonephritis Dangerous w/ DM or advanced
54
Renal abscess diagnosis and treatment
Ua: wbc, bacteria, protein hematuria, **pyuria** CT for dx after UA, CBC (leukocytes), ESR/CRP = inflammation Tx: Ampicillin + aminoglycosides + I&D if \>5cm Nephrectomy is last resort
55
Acute pyelonephritis
Affects renal cortex, spares glomeruli and vessels UA: wbc casts - formed in DCT E. coli, proteus, Klebsiella, enterobacter Treat aggressively in DM, pregnancy to prevent abscess
56
Emphysematous Pyelonephritis
Necrotizing infection w/ gas formation In poorly controlled DM, immunocompromised Rapidly progressive -\> fulminant sepsis w/ high mortality
57
Acute Pyelonephritis symptoms and diagnosis
Sx: Shaking chills, fever, arthralgia/myalgia, flank/CVA pain -urgency/frequency urination, V/D in peds Dx: UA: wbc casts, bacteria, hematuria - culture Get blood cultures and CBC (left shift) CT for dx - hydronephrosis or inflammation/infection US for obstruction
58
Acute Pyelonephritis Treatment
Ampicillan (IV) - until 24 hours after fever resolves Cipro/ofloxacin/Aminoglycosides/Bactrim PO 14 days after Follow up w/ urine culture to confirm resolved Refer if complicating factor (stone, reflux, tumor, neurogenic bladder) Watch for sepsis: tachypnea, AMS
59
Chronic Pyelonephritis hallmarks
Recurrent/persistent renal infections, usually w/ major anatomical abnormalities (VUR) Asymmetric corticomedullary scarring/thyroidization Eosinophilic casts in tubule **Chronic Pye and TEA:** thyroidization, eosinophilic casts, asymmetric scarring
60
Vesicoureteral reflux (VUR)
Kids w/ UTI - screen Hydronephrosis @ birth, frequent UTIs, bedwetting Primary: congenital muscular deficiency Secondary: bladder outlet/functional obstruction Detect w/ UA, VCUG and US - febrile/male UTI, \<5yo w/ UTI
61
Chronic Pyelonephritis symptoms and diagnosis
Sx: fever, lethargy, N/V, flank pain, dysuria, failure to thrive (kids) Dx: UA: wbc, bacteria, hematuria IVP is test of choice - calyceal dilation and blunting w/ cortical scars VCUG, cystoscopy to document VUR
62
Chronic Pyelonephritis Treatment
Stage 1&2: Chronic Abx prophylaxis until puberty - Amox, Bactrim, Septra, Nitrofurantoin Stage 3&4: VUR = surgery w/ ureter reimplantation -Surgery indicated w/ noncompliance, reflux past puberty, breakthrough infections Aggressively tx UTIs Dietary and BP control, routinely screen pregnant and FH
63
Xanthogranulomatous pyelonephritis (XPN)
Chronic obstruction complication w/ infected stones Massive kidney destruction, need immediate nephrectomy Sx: adults - looks like pyelo w/ palpable flank mass and CVA tenderness Children: type 1 affects genders equally, hits entire kidney Type 2 hits girls, looks like Wilm's tumor 1/2 have palpable mass, growth/weight retardation
64
XPN diagnosis and treatment
Dx: UA: pyuria, bacteriuria, culture reveals G(-) organism -E. coli, Proteus, Klebsiella; staph is rare Anemia, increased ESR, LFTs w/ hepatomegaly Tx: surgical removal + Abx -can be partial if localized (kids) or bilateral dx
65
Cystitis
Coliform (E.coli)/G+ (entercoccus) bladder infection -Viral may occur in kids Sx: irritative voiding, suprapubic pain, hematuria Dx: UA - leukocyte esterase, nitrites, +/- blood Tx: 1-3 days Nitrofurantion (pregnancy), Bactrim/Septra, fluroquinolones Additional testing if male, recurrent, anatomic abnormality
66
Nephrotic Syndrome Pathophysiology
Glomerular capillary wall breakdown/Electrostatic charge lost Proteinuria occurs = Vit D deficiency, PTH increase (low Ca) -24 hour UA to quantify protein loss Hypoalbuminemia = decreased oncotic pressure = edema and hyperlipidemia Hyperlipidemia from increased hepatic synthesis = lipiduria
67
Minimal Change Disease
Nephrotic Syndrome in kids Children, Adults w/ NSAIDs Mild mesangial cell proliferation, flattened podocytes Idiopathic, drugs, allergies, HL/Leukemia Tx: Steroids 4-8 wks, 16 for adults -continue after proteinuria resolves
68
Focal Segmental Glomerulosclerosis (FSGS)
Nephrotic syndrome Mesangial collapse and sclerosis in 1/2 glomeruli Black, idiopathic nephrotic syndrome Secondary cause: HIV, obesity, DM, lupus, nephrotoxic meds/chemicals Tx: primary: diuretics, ACEI, statins, high-dose steroids 4-16 wks
69
Membranous Nephropathy
Most common nephrotic syndrome in adults (5th-6th decade) Basement membrane thickened w/ immune complex or electron dense deposits Primary: idiopathic, autoantibodies Secondary: Hep B/C antigenemia, AI, CA, drugs (gold, captopril, NSAIDs) Protein leaked despite thickening due to damage electrostatic charge
70
Nephrotic Syndrome Complications
Infection Edema Hypovolemia HTN Acute renal failure Protein malnutrition Thromboembolism (hypercoagulable w/ hypovolemia) Vitamin D/Calcium deficiency
71
Nephrotic Syndrome diagnosis and treatment
24 hour UA Kidney biopsy - definitive Dx Triad: proteinuria, edema, hypoalbuminemia Tx: ACEI/ARB for proteinuria - diuretics/sodium restriction (edema) - Statins until cured (hyperlipidemia) - Anticoagulate w/ DVT (hypercoagulability)
72
Systemic disorders causing Nephrotic disease
Amyloidosis Diabetic Nephropathy HIV-associated nephropathy Hepatitis C Multiple Myeloma Sickle-cell disease Tuberculosis Gout
73
Amyloidosis
Protein deposits in organs (mesangium and capillary loops) Dx: UA w/ amyloiduria, biopsy, CT to evaluate extent Tx: Dialysis, progress to ESRD w/ in 2-3 years 5 year survival (w/ heart affected too) \<20%
74
Diabetic Nephropathy
Most common ESRD cause - not always diabetes-induced -Check onset, rbc/casts, another systematic dx, or ACEI/ARB Microalbuminuria = screen w/ dipstick, 24 hour test to confirm Intraglomerular HTN and hyperglycemia contribute to destruction Tx: control sugars, BP, lipids, weight loss, Na restriction, loop diuretic
75
HIV-Associated Nephropathy
Nephrotic presentation Need renal biopsy to confirm = FSGS pattern HAART slows progression, consider steroids + cyclosporine and ACEI
76
Systemic Lupus (SLE)
Nephritic presentation most common Monitor UA and chem panel Biopsy to confirm Tx: steroids Different types - membranous nephropathy is worst
77
Hepatitis C
Mixed nephrotic/nephritic pattern 80% ESRD pts also have this Hematuria, proteinuria, HTN, anemia, hypocomplementemia Tx: only w/ poor renal function, nephrotic, increased HTN, or fibrosis on bx -INF to suppress viremia and improve renal function (9month dose) SE INF: flu-like, weight loss, fatigue, fever
78
Multiple Myeloma
Malignant plasma cells w/ Bence-Jones protein loss Dx: serum electrophoresis w/ Bence-Jones on UA + hypercalcemia and urea Tx: Correct Calcium, volume - Chemo for underlying Ca - plasmapheresis doesn't help kidney
79
Sickle-cell disease
Nephrotic presentation Papillary necrosis Hematuria, isosthenuria (urine osmolality = serum), proteinuria Tx: Hydration, control dx
80
Tuberculosis
Microscopic pyuria w/ sterile urine - culture for Dx -need high suspicion/positive PPD for media Tx: treat TB
81
Gout
Overproducers or Underexcretors of uric acid PCT dysfunction results in uric buildup Tx: diet, hydrate, Allopurinol/Colchicine (reduce uric acid)
82
Acute Renal Failure/Acute Kidney Injury
Abrupt (w/in \<48 hrs) decline in kidney function -Increased SCr or decreased output or dialysis needed Sx: N/V, malaise, HTN, pericardial effusion/rub, arrhythmias, abdominal pain, encephalopathic changes
83
BUN and Creatinine increases
BUN: burn, tetracycline, steroids, fever, GI bleed, catabolic state -converted from ammonia in liver Creatinine: secretion blocked by cimetidine or Trimethoprim
84
Acute Kidney Injury labs
Increased BUN/Creat, hyperkalemia, hyperphosphatemia Decreased GFR, hypocalcemia, anemia Platelet dysfunction Anion gap metabolic acidosis
85
Pre-renal AKI
Lack of blood flow to glomerulus -ACEI/ARB (efferent) or NSAIDs (afferent) cause vasodilation Urine has low sodium, high osmolality due to low perfusion-\> increased Na/H2O absorption Tx: underlying cause, maintain euvolemia and electrolytes -Avoid nephrotoxic drugs, may need short dialysis course
86
Post-renal AKI
Reversible, least common AKI cause (BPH usually) Sx: olig/anuria, lower back/abdominal/flank pain, enlarged prostate/pelvic mass (**rectal exam**), distended bladder Dx: US, Catheterization, CT for stones/hydronephrosis -BUN/Creat 10-20:1 Tx: Bladder catheter, refer to Urology for stent/resection/nephrostomy
87
Intrinsic AKI
Most common AKI Caused by: - Acute Glomerulonephritis - Acute Interstitial Nephritis - Acute Tubular Necrosis - Contrast Nephropathy (ATN form)
88
Acute Glomerulonephritis
Inflammation/proliferation of glomerular tissue -damages basement membrane, mesangium, capillary endothelium Sx: rbc casts, significant proteinuria PSGN, Systemic (lupus, Wegeners, Goodpasures)
89
Acute Interstitial Nephritis
Medications, bacteria/viral/fungal infection Eosinophils on UA Maculopapular rash, fever, arthralgias
90
Acute Tubular Necrosis
Most common intrinsic injury Ischemia, sepsis, nephrotoxic drugs -\> tubules fail to function UA: Deeply pigmented, coarse granular casts are hallmark
91
Nephrotoxic drugs
Aminoglycosides Ampho B Chemo Acyclovir Ethylene glycol Sulfa Cephalosporins
92
Contrast Nephropathy
Form of ATN 24-48 hours post exposure Prevention: minimize contrast, Mucomyst, hydrate, stop Metform for 48 hrs after
93
Fractional excretion of sodium and urine sodium concentration (FENa)
Determine if AKI cause is prerenal or ATN 100\* (UNa x SCr)/(SNa x UCr)
94
AKI Management and general workup
Maintain euvolemia, electrolytes, BP - stop potentially nephrotixic meds - may need temporary dialysis Workup: Assess volume status, UA, CBC, BUN/Creat (BMP), FENa
95
Respiratory acidosis
Increase ventilation to correct Low pH with high CO2 Causes: CNS depression, hypoventilation, impaired respiratory muscle function, pulmonary disorders
96
Respiratory Alkalosis
Increased pH with decreased CO2 - hyperventilation Causes: Psychological response, medications, increased metabolic demand, CNS lesion
97
Metabolic Acidosis
Lack of bicarb OR too much acid - GI/renal loss - Renal failure, DKA, ASA overdose, hypoxic tissue Anion gap narrows down etiology
98
Increased Anion Gap Metabolic Acidosis
MUDPILES Methanol intoxication Uremia DKA/Alcoholic Paraldehyde Isoniazid/Iron overdose Lactic acid Ethylene glycol Salicylate overdose
99
Anion Gap
Na - (HCO3+Cl) Normal = 12 +/-4 \>20 = High serum AG =\> metabolic problem always
100
Non-Anion Gap Metabolic Acidosis
USED CAR Ureteral-sigmoid diversion (pee into intestine) Small bowel fistula/Saline administration Endocrinopathies (Addisons, HyperPTH) Diarrhea Carbonic anhydrase inhibitors (hyper)Alimentation (supplementary/artificial nutrition) Renal tubular acidosis
101
Metabolic Alkalosis
Too much bicarb Gastric suctioning, vomiting, diuretics, antacids Check Cl here -\> chloride-responsive if UCl \<10 -Chloride-resistant if UCl\> 10 =\> Mineralocorticoid problem Contraction alkalosis with large volume loss (diuretics) but bicarb remains the same
102
High serum anion gap
R/o DKA/alcoholic or lactic acidosis
103
Delta Gap
Used for Metabolic acidosis Calculate how abnormal AG is measuredAG - 12 = change anion gap 24-HCO3 = changed bicarb AG\>BC = metabolic acidosis also present (mixed disorder) AG

AG = BC +/-2 = no additional issue

104
Winter's Formula
Metabolic acidosis Determine if underlying concomitant respiratory disorder PaCO2 = 1.5(HCO3)+8 +/-2 OR PCO2 = digits of pH PCO2\>PaCO2 = concomitant respiratory acidosis PCO2

+/-2 = each other => no underlying disorder

105
Summer's formula
Metabolic Alkalosis Calculate respiratory compensation PaCO2 = 0.7(HCO3 +21) +/-2 PCO2\>PaCO2 = respiratory acidosis PCO2