Converts aspartate (Asp) and alpha ketoglutarate (alpha-KG) to oxaloacetate (OAA) and glutamate

Asp + alpha KG (to) OAA + glutamate + NADH (to) malate + NAD

Disapppearance of NADH reflects AST activity

p-nitrophenyl phosphate (to) p-nitrophenol + phosphate

(it catalyzes this reaction; p-nitrophenol absorbs at 405 nm while pnp does not)

Serum enzyme inhibitors

Lack of necessary cofactor

Macroenzymes

Defective enzyme

Proteolytically inactivated enzymes

Y: 1/Vmax

X: -1/Km

Noncompetitive inhibition?

Vmax change?

Km change?

Inhibitor that binds to the enzyme AWAY from the substrate binding site

1/Vmax changed

1/Km unchanged

Enzyme's substrate and inhibitor compete for SAME binding site

1/Vmax unchanged

1/Km changed

-Can be overcome by increased substrate concentration

When a substance binds the Enzyme-Substrate (ES) complex and stabilizes it

Vmax and Km changed

Heart

Liver

Skeletal muscle

Kidney

Brain

Lung

Pancreas

Cytoplasm (20%)

Mitochondria (80%)

LD1 and 2 (fast): heart, RBC, kidney

LD4 and 5 (slow): liver, skeletal muscle

lung

spleen

lymphocytes

pancreas

1. MI complicated by liver congestion

2.Chronic alcoholism with megaloblastic anemia

Red cells

Prostate

 Bone

Bone

Bile ducts

Intestine

Placenta

Alkaline phosphatase increased?

Bone disease, Bone growth (children)

Biliary disease

Pregnancy

Hypophosphasia (inborn)

Malnutrition

Heat/Urea inhib | L-phe inhib | Anodal Mobility

Biliary

Bone

Placenta

Intestinal

Regan

Heat/Urea inhib | L-phe inhib | Anodal Mobility

Biliary        +                    -                       1

Bone          +++               -                       2

Placenta        -                 +++                   3

Intestinal      +                 +++                  4  

Regan           -                  +++                  3

Lewis positive type B or O secretors

*Ingesting a meal can elevate it by 30% for 2-12 hours

Unrecognized pregnancy

CHF

Hyperthyroidism

Drugs (ibuprofen, acetaminophen)

*In F middle age, test for antimitochondrial antibodies (primary biliary cirrhosis)

Smooth endoplasmic reticulum

(thus increased when pts take warfarin, barb, dilantin, valproate, methotrexate, alcohol)

Skeletal muscle

Gut (bacteria break down protein and release ammonia)

Bilirubinuria indicates unconjugated or conjugated hyperbilirubinemia and why?

Conjugated

B/c it is water soluble

Diazo-colorimetric method

(without addition of accelerator, conjugated is mearusured. with accelerator, total is measured)

Unconjugated Hyperbilirubinemia

Heme conversion 

Delivery of u.b. to liver

Uptake of u.b. into hepatocyte

Conjugation of b. in hepatocyte

Unconjugated Hyperbilirubinemia

Heme conversion                     Hemolysis(extravasc)

Delivery of u.b. to liver             Blood shunt (cirr);RHF

Uptake of u.b. into hepatocyte   Gilbert, Drugs: rifampin

Conjugation of b. in hepatocyte  Crigler Najar;                                                             Hypothyroidism

Step                                     Pathologic Process        [Conjugated Hyperbili]

Transmembrane secretion of c.b. into canaliculus

Flow of co. thru canaliculi and bile ducts (cholestatic jaundice)

Step                                     Pathologic Process        [Conjugated Hyperbili]

Transmembrane secretion of c.b. into canaliculus

-Dubin Johnson , Hepatitis, Endotoxin (sepsis), pregnancy (estrogen), drugs:estrogen, cyclosporine

Flow of co. thru canaliculi and bile ducts (cholestatic jaundice)

-mechanincal (PBC, PSC), tumor, stricture, stone

When conjugated hyperbilirubinemia persists for a long time, cb can be covalently linked to serum albumin, thus delta bilirubin.

It is incapable of being excreted by either liver or kidney

In autoimmune hepatitis, polyclonal increase in what immunoglobulin?

In prmary biliary cirrhosis?

IgG (AH)

IgM (Primary biliary cirrhosis)

What happens to the Albumin/Globulin ratio in liver disease?

Decreases

A/G <1 (u) due to liver disease

(albumin not being produced as much with concomitant increase in production of globulins)

Physiologic jaundice

Breast milk

Polycythemia

Hemolysis (HDN, hemogbopathies, inherited membrane or enzyme defects)

Bowel obstruction (Hirschsprung, CF, ileal atresia)

Inherited disorders (Gilbert, Crigler Najar)

Biliary obstruction (extrahepatic biliary atresia)

Sepsis/TORCH

Neonatal hepatitis (idiopah, Wilson, Alpha1AT)

Metabolic disorders (galactosemia, hereditary fructose intolerance, glycoen storage disease)

Inherited (Dubin Johnson, Rotor)

Parenteral alimenation

HDN

Sepsis

Appearance w/in first 24 hours

Rising bili past 1 week

Persistence past 10 days

T bili > 12

Single day increase >5

d bili > 2 (mg/dL)

Jaundice in 1st 24 h?

between 3rd and 7th day?

After first week?

1: Erythroblastosis fetalis, concealed hemorrhage, sepsis, TORCH

2: bacterial sepsis (UTI common)

3:breast milk, sepsis, extrahep b. atresia, CF, Alagille (cong paucity of bile ducts), neonatal hepatitis, galactosemia, inherited hemolytic anemia (PK def, HS, G6PD)

50% of acute viral hepatitis;

Rarely reaches this level in alcoholic hepatitis

Toxic

Ischemic

Alcoholic

(u <1 in viral hepatitis)

Jaundice Percentages

Alcoholic hepatitis and Acute Hepatitis A?

Hepatitis B and C?

Toxic and ischemic injury?

70%

25%

Rare

6 bands

Salivary 3 are fast

Pancreatic 3 are slow

FE = Cl(x)/Cl(creatinine)

[Cl(creatinine) = GFR]

Hypertriglyceridemia

(TG competitively interfere with the amylase assay)

(All White Guys Like Asians)

Age > 55

WBC >16

Glucose >11 mmol/L

LDH >350

AST > 250

Urea>1.8 mmol/L increase

Calcium <2mmol/L

PaO2 <60mmHg

Base Deficit >4

Fluid sequestration >6L

Hematocrit >10 decrease

 BF CUP H

'Best Friends CUP Hooray!'

Gallstone pancreatitis

(95% specific, 50% sensitivity)

Mumps

Coxsackie

CMV

VZV

HSV

Hepatitis B

HIV

CK BB - fastest

CK MB - middle

CK MM - slowest

CK BB location?

CK MM?

CK MB?

BB: brain (bladder, stomach, prostate)

MM: skeletal muscle (99%), cardiac (70%)

MB: cardiac (30%), skeletal (1%)

Hemolysis

CK BB (stroke)

Macro-CK

What is Macro-CK?

Migration?

Found in what population?

It is a CK-Ig complex

Between CK MM and CK MB

Elderly women

Close to CK MM (u slower)

In patients with advance malignancies and assw poor prognosis

cTnI

(Also cTnT good, but marginally less cardio specific. Both I and T encoded by diff genes resp in heart and muscle; but C encoded by same gene in both)

                                            Amylase|CEA | CA19-9

Pseudocyst                            

Serous cystadenoma

Mucinous Cystadenoma

IPMN

Solid pseudopapillary tumor

Pseudocyst                   A: up, CEA: down, CA: up

Serous cystadenoma       A: down, CEA: down, CA: down

Mucinous Cystadenoma  A: down, CEA: up, CA: nl/up

IPMN                           A: up, CEA: up, CA: nl/up

Solid pseudopapillary     A: down, CEA: down, CA: down

Protein quantiation thru measurement of nitrogen content; involves acid digestion of proteins that release ammonium ions

In an alkaline medium, copper salts form a purple complex with proteins.

Absorbance at 540 nm is proportional to total protein concentration

210 and 280

(absorbance is proportional to protein content)

Protein electrophoresis

Solid support charge?

Endosmosis pulls proteins towards which pole?

Protein electrophoresis

Solid support charge?  -- Negative

Endosmosis --- towards the cathode (negative pole)

Similar to gel. Capillary tube that contains buffer. Sample introduced. Voltage applied. depending on molecular size and charge, molecules elute at different times.

Advantages just include small sample size, automation, increased sensitivity for M proteins

Most common allotype of albumin?

When are 2 albumin peaks seen?

Best clinical utility of albumin?

Half-life of albumin?

Acute phase reactant?

Most common allotype of albumin? - Albumin A

When are 2 albumin peaks seen? Bisalbuminemia

Best clinical utility of albumin? Nutritional status

Half-life of albumin? - 17 days

Acute phase reactant? - Negative APR

2 main functions of pre-albumin?

Alternative names?

Clinical utility?

Half-life?

Acute phase reactant?

Binds T4 and T3

Transthyretin, Thyroxine binding pre-albumin

Also binds retinol binding protein vitamin A complex

Clinical utility? :  nutritional status 

Half-life: 2 days

APR? Negative acute phase reactant 

Why is there a prominent "pre-albumin band" in heparinized patients?

True elevations in pre-albumin seen when?

Alteration in Beta-lipoprotein so that it migrates in pre-albumin range.

True elevations in pre-albumin seen when?

Chronic alcoholics

Corticosteroid therapy

Possible useful role of alpha1 glycoprotein?

Monioring activity of chronic inflammatory conditions such as UC. Increased with acute inflammation

Alpha 2 macroglobulin elevated when?

Protease inhibitor; Elevated in liver and renal disease. Large size prevents clearance in nephrotic syndrome.

Ceruloplasmin decreased in what conditions?

Falsely normal or elevated ceruloplasmin seen when?

Ceruloplasmin decreased in what conditions?

Wilsons

Hepatic failure

Malnutrition

Menke Syndrome

Falsely normal or elevated ceruloplasmin seen when?

Inflammatory states (+APR), pregnancy

Transferrin function?

Level in iron deficiency?

Why are there two peaks in CSF protein electrophoresis?

Transferrin function? - Transports ferric iron (3+), normally 30% saturated.

Level in iron deficiency? Increased (also up in pregnancy and estrogen therapy)

Why are there two peaks in CSF protein electrophoresis? before crossing blood/brain barrier, a certain % becomes asialated (aka Tau protein)

In protein electrophoresis, where is fibrinogen located?

When is it present in the serum?

Beta globulin with caveats. Can straddle beta-gamma interface and be misinterpreted as M protein.

When is it present in the serum?

Dysfibrinogemia, APL syndrome, liver disease, vitamin K deficiency, heparin

CRP produced where?

3 categories?

Used how?

CRP produced where? - Liver

3 categories? Normal (<3), low level 3-10, high >10

Used how? low level predict poor outcome after heart events. (Used to support diagnoses such as bacterial endocarditis, appendicitis, active collagen vascular disease)

Serum electrophoresis

Normal Serum?

Large albumin band

Small peaked alpha 1

alpha 2

bimodal beta band

broad gamma

Serum electrophoresis

Nephrotic syndrome?

-Results in massive loss of small serum proteins, particularly albumin.

-When due to minimal change disease, especially selective loss of albumin.

-In all other forms, nearly all proteins are lost including gamma globulins

-In all types, larger proteins are retained. Result is dimming of all electrophoretic bands most prominently the albumin band with exception of alpha2 band(alpha2 macroglobulin

Serum electrophoresis

Acute inflammation?

Hallmark of cirrhosis. Attributed to increased serum IgA.

(additional features include hypoalbuminemia, blunted alpha 1 and alpha 2 bands)

Myeloma (10% of patients- more likely to have free light chains in urine)

Congenital hypog.

Lymphoma

Nephrotic syndrome

Corticosteroid tx

M-spike

Clinical suspicion

Systemi AL amyloidosis

Hypogammaglobulinemia

After a diagnosis of M Myeloma, things to monitor?

M-protein quantity

Quantify other Ig (assess degree of supression)

Serum free light chains- quantify

Assess kappa/lambda ratio

Hyperviscosity syndrome Sx?

Should be measured when?

Hyperviscosity syndrome Sx?

Nasal bleeding, vision (blurred, veins dilated with flame shaped hemorrhages) neurologic (HA, tinnitus, hearing loss, ataxia, diplopia)

Should be measured when? Normal 1.5 - 1.8 cp

IgM > 4g/dL

IgA or IgG > 6g/dL

CSF protein electrophoresis main characteristics?

Main clinical use?

Pre-albumin - prominent

Double beta (transferrin) band

Subtle: dim albumin, alpha 2 band

Clinical: Assess for multiple sclerosis

UPEP Glomerular proteinuria?

Strong albumin, alpha 1, beta bands

(glomerulonephritis u responsible. very large proteins due to tubular reabsorption do not appear)

UPEP Tubular proteinuria?

Weak albumin

Strong alpha 2 ? and Beta bands

(results from impaired reabsorption of low molecular wieght proteins normally freely filtered. ; etio include tubulointerstitial nephritis or ATN)

UPEP Overflow proteinuria?

MC a monoclonal light chain (Bence Jones)

Other etio include: myoglobin, hemoglobin

Collection practices to detect cyroglobulins?

Blood drawn at 37 C and kept until clotted. Then centrifuged. Remaining serum stored at 4 C for 3 days and then centrifuged.

Any precipitate is a cryoprecipitate that can be electrophoresed.

Type I: monoclonal Ig (assw MM or Waldenstrom)

Type II: mix of monoclonal IgM and polyclonal IgG

(IgM has rheumatoid factor activity (anti IgG) ; this is the MC type of cyroglobulin)

Type III: mix of 2 polyclonal Ig

Clinical scenarios with mixed cyroglobulinemia (types II and III)?

MC: HCV

Lymphoproliferative

Chronic liver diseases

Autoimmune (SLE)

(common in F 4 & 5th decades)

Palpable purpura (LCV) - constant feature

Arthralgias

Hepatosplenomegaly

Anemia

Sensorineural defects

Glomerulonephritis

Membranoproliferative glomerulonephritis

(MPGN II)

(large subendothelial deposits)

UPEP: Glomerular proteinuria pattern?

STRONG: albumin band

alpha1 and B bands

(very large proteins (filter) and very small proteins (reabsorption) do not get out. Leaving proteins in between - albumin, AAT, transferrin)

UPEP: Tubular proteinuria pattern?

WEAK: albumin band

STRONG: alpha 1, alpha 2, Beta bands

(impaired reabsorption of low molecular weight proteins - alpha 2 macroglobulin, b2 microglobulin, light chains)

UPEP: Overflow proteinuria pattern?

MC monoclonal light chain (Bence Jones)

~myoglobin, hemoglobin

Difference between Cyroglobulins

Type I

Type II

Type III

Difference between Cyroglobulins

Type I : monoclonal Ig assw MM or Waldenstroms

Type II : mixture of monoclonal IgM and polyclonal IgG. IgM has RF activity (anti-IgG). MC type.

Type III: mixture of 2 polyclonal Ig.

Mixed cyroglobulinemia

MC etiology?

Other causes?

Clinical Sx?

Tx?

Mixed cyroglobulinemia

MC etiology? HCV

Other causes? Lymphoproliferative, infxns chronic, chronic liver diesase, autoimmune (SLE)

Clinical Sx? Palpable purpura (LCV), arthralgias, HSmegaly, sensorineural, glomerulonephritis (MPGN II -large subendothelial deposits)

Tx? Immune modulation

Too rapid correction of hyponatremia?

Too slow a correction?

Too rapid correction of hyponatremia?

-Central pontine myelinosis

Too slow a correction?

-Cerebral edema

Pseudo-hyponatremia etiologies?

Hyper- (glycemia, lipidemia, proteinemia)

Hyponatremia - Hypovolemic

Renal losses?

Extrarenal loss?

Hyponatremia - Hypovolemic

Renal losses? Una> 30mmol/L : diuretics, medullary renal disease, Addison, RTA1

Extrarenal loss? UNa<30 : GI losses, third spacing

Hyponatremia - Euvolemic etiologies?

Hyponatremia - Euvolemic etiologies?

SIADH

Psychogenic polydipsia

Drugs (ADH-like including desmopressing, SSRIs, TCAs)

Hyponatremia: Hypervolemic?

Hypernatremia: Hypervolemic?

CHF, Cirrhosis, Nephrotic Syndrome

Hypernatremia: water loss etiologies?

Hypernatremia: water loss etiologies?

Diabetes insipidus, DM

Diarrhea

Osmotic diurectics,

Sweating

Hypokalemia: GI losses?

Renal losses?

Transcellular Shifts?

Hypokalemia: GI losses?

Vomiting, NG tube

Diarrhea, Villous Adenoma

Renal losses?

Diuretics, Hypomagnesemia

Antibiotics (carbenicllin, amphoB), Mineralocorticoids

RTA 1&2

Cushing, CAH, Hyperreninism

Transcellular Shifts? Alkalosis, Correction of DKA

Primary hyperparathyroidism

Calcium?

Phosphate?

Chloride?

Nephrogenous cAMP?

Primary hyperparathyroidism

Calcium? Increased

Phosphate? Decreased

Chloride? Increased

Nephrogenous cAMP? Increased

In DKA, ketoacidosis assw hyperkalemia.

Upon correction of DKA, profound hypokalemia. Potassium supplementation important.

Passive transmembrane potassium leak from RBCs without hemolysis assw what mutation?

Familiarl pseudohyperkalemia - AD xsome 16

Differential diagnosis of hyperkalemia?

Acidosis

Renal failures

Potassium sparing diuretics (spironolactone)

Adrenal insufficiency

Rhabdomyolysis

Iatrogenic

DDx Hypercalcemia?

DDx Hypercalcemia?

Primary Hyperparathyroidism (adenoma, hyperplasia)

Tertiary HP (post-renal transplant)

Malignancy (SCCa, MM, Breast, Paraganglioma, RCC, HCC)

Familial hypocalciuric hypercalcemia (CASR on 3q)

Drugs

Endocrine (Hyperthyroidism, Addison, acromegaly)

Granulomatous disease (Sarcoidosis)

Paget

Occurs in post-renal transplant patients

Parathyroids become autonomous and enlarged

Intact PTH

N-terminal PTH : Biologically active, short half life

Mid-region PTH

C-terminal PTH: Inactive, long half-life

Increases proportion of free calcium (bc it competes for binding sites on albumin)

Likewise, alkalosis decreases proportion

In secondary hyperparathyroidism (peripheral resistance of PTH usually seen in chronic renal failure).

Ca low, PTH nl to high, Phosphate high

*Persistent osteoclast activation leads to brown tumors (renal osteodystrophy)

Effect of persistent hypomagnesemia on PTH?

Inhibits PTH secretion

Hypocalcemia effects?

EKG?

Hypocalcemia effects?

Neurologic exciteability

Muscle spasms

Hyper-reflexia

Paresthesias

EKG?
QT interval prolonged

low voltage T wave

Respiratory acidosis?

Respiratory alkalosis?

Respiratory acidosis?

Hypoventilation; too little elimination of CO2

Respiratory alkalosis?

Hyperventilation; too much elimination of CO2

Henderson Hasselbach Equation?

pH=pKa + log(base/acid)

[normal 7.4 = 6.1 + log (24 bicarb/1.2 dissolved paCO2)

7.4 = 6.1 + 1.3

ABG measures what?

pH electrode

PaCO2 electrode

PaO2 electrode

(all directly measured)

Derives oxygen % saturation (calculation that assumes normal Hb affinity)

Co-oximeter measures what?

Spectrophotometric device

Measures multiple wavelengths, and measures (not calculates) proportions of deoxy, oxy, meth, and carboxy-hemoglobin

O2 % saturation calculated via ratio.

Anion gap = ?

Corrected AG = ?

Anion gap = ?

AG= [Na} - ([Cl] + [HCO3])

Corrected AG = above + 2.5( 4-albumin)

Differential for Low Anion Gap?

Differential for Low Anion Gap?

Paraproteinemia

Hypoalbuminemia

Hypermagnesemia

Hypercalcemia

Lithium therapy

Hypophasphatemia

Osmolal gap = ?

Osmolal gap =

Osm (measured) - [2(Na) + Glucose/18 + BUN/2.8]

Delta - delta?

-Comparison of the (bicarbonate change) and (anion gap change).

-Changes should be 1:1 in simple acid-base disorders

-Delta-delta greater than that indicates complex disorder

pH and HCO3

Metabolic acidosis?

Respiratory acidosis?

pH and HCO3

Metabolic acidosis?

-in same direction (HCO3 < 25)

Respiratory acidosis?

-in opposite directions (pCO2 > 44)

pH and HCO3

Metabolic alkalosis?

Respiratory alkalosis?

pH and HCO3

Metabolic alkalosis?

-pH and HCO3 in same direction (bicarb >25)

Respiratory alkalosis?

-pH and HCO3 in opposite directions (CO2 < 40)

Pattern Associated with Edward's Syndrome?

Neural tube defects?

Down's Syndrome?

Pattern Associated with Edward's Syndrome?

Decreased AFP, Decreased hCG, Decreased Estriol

Neural tube defects?

Increased AFP, Normal hCG, Decreased Estriol

Down's Syndrome?

Decreased AFP, Increased hCG, Decreased Estriol, Increased inhibin

Definition of premature labor?

Definition of premature labor?

Regular contractions

Associated cervical changes

Prior to 37 weeks

Primary component of lecithin?

Good L:S ratio?

What can measured in lieu of L:S?

Primary component of lecithin?

Phosphatidylcholine

Good L:S ratio?

2:1

What can measured in lieu of L:S?

Phosphatidyl Glycerol

Autoimmune diseases ameliorated by pregnancy?

Worsened?

Autoimmune diseases ameliorated by pregnancy?

RA

Graves

Worsened?

SLE

Myasthenia Gravis

Metabolic Acidosis: Increased Anion Gap?

Metabolic Acidosis: Increased Anion Gap?

Methanol

Uremia

Ketoacidosis- Diabetic, EtOH, Starvation

Paraldehyde

Lactic Acidosis

Ethylene Glycol

Salicylate

Metabolic Acidosis: Normal Anion Gap?

Metabolic Acidosis: Normal Anion Gap?

Diarrhea

DKA - recovery phase

Ureterosigmoidostomy

RTA

Carbonic anhydrase inhibitors

TPN

NH₄Cl

Appropriate Compensation

Metabolic acidosis: For each __ mEq fall in [HCO₃], the pCO₂ decreases by __ mm Hg?

Metabolic alkalosis: For each __ mEq rise in [HCO₃], the pCO₂ increases by __ mm Hg?

Appropriate Compensation

Metabolic acidosis: For each _1.3_ mEq fall in [HCO₃], the pCO₂ decreases by _1.0_ mm Hg?

Metabolic alkalosis: For each _0.6_ mEq rise in [HCO₃], the pCO₂ increases by _1.0_ mm Hg?

Acidosis

Metabolic acidosis: pH and HCO₃ relationship?

Respiratory acidosis: pH and HCO₃ relationship?

Acidosis

Metabolic acidosis: pH and HCO₃ relationship?

-Same direction (bicarbonate <25 mEq/L)

Respiratory acidosis: pH and HCO₃ relationship?

-Opposite direction (pCO₂ > 44 mm Hg)

Alkalosis

Metabolic alkalosis: pH and HCO₃ relationship?

Respiratory alkalosis: pH and HCO₃ relationship?

Alkalosis

Metabolic alkalosis: pH and HCO₃ relationship?

-Same direction (bicarbonate > 25 mEq/L)

Respiratory alkalosis: pH and HCO₃ relationship?

-Opposite direction (pCO₂ < 40 mm Hg)

Respiratory alkalosis/acidosis

Acute: For each __ mm Hg change in pCO₂, the HCO₃ changes by __ in the __ direction

Chronic: For each __ mm Hg change in pCO₂, the HCO₃ changes by __ in the __ direction

Respiratory alkalosis/acidosis

Acute: For each _1_ mm Hg change in pCO₂, the HCO₃ changes by _0.1_ in the _same_ direction

Chronic: For each _1_ mm Hg change in pCO₂, the HCO₃ changes by _0.4_ in the _same_ direction

Correct Anion Gap  = 

AG + 2.5 (4 - albumin)

Increased Osmolal Gap: With Metabolic Acidosis?

Increased Osmolal Gap: With Metabolic Acidosis?

Methanol

Propylene glycol

Diethylene glycol

Paraldehyde

Ethanol (~)

Increased Osmolal Gap: WithOut Metabolic Acidosis?

Increased Osmolal Gap: WithOut Metabolic Acidosis?

Isopropyl alcohol

Gycerol

Sorbitol

Mannitol

Acetone

Ethanol (~)

Metabolic Alkalosis: Chloride Response (U_Cl < 10) ?

Metabolic Alkalosis: Chloride Response (U_Cl < 10) ?

Diuretics

Vomiting

NGTube Suction

Villous Adenoma

Carbenicillin

Contraction Alkalosis

Metabolic Alkalosis: Chloride Response (U_Cl > 10) ?  ()

Metabolic Alkalosis: Chloride Response (U_Cl > 10) ?

Hyperaldosteronism

Cushing Syndrome

Exogenous Steroids

Licorice (glycrrhizic acid)

Bartter syndrome

Milk-alkali syndrome

GFR calculation?

GFR = Creatinine clearance

Cr_Cl = (U_Cr x V_Ur) / P_Cr

MDRD Equations

Original non traceable (mg/dL ; 88.4 for umol/L)

Traceable (mg/dL ; 88.4 for umol/L)

MDRD Equations

Original non traceable (mg/dL ; 88.4 for umol/L)

eGFR = 186 x Sc/(88.4)^-1.154 x age^-0.203

Traceable (mg/dL ; 88.4 for umol/L)

eGFR = 175 x Sc/(88.4)^-1.154 x age^-0.203

Normal BUN/Cr ratio (but both elevated)?

BUN/Cr elevated?

Normal BUN/Cr ratio (but both elevated)?

-Renal disease (glomerulonephritis, tubulointerstitial nephritis)

BUN/Cr elevated?

-Pre-renal (hypovolemia, hypotension)

-Post-renal (obstruction)

Normal proteinuria?

Significant proteinuria?

Normal proteinuria?

<150mg/day

Significant proteinuria?

>300mg/day

DDx of high urine [protein] and negative microalbumin assay?

DDx of high urine [protein] and negative microalbumin assay?

-Hook effect

-Bence Jones proteinuria

B2 microglobulin and lyzozyme presence in urine?

B2 microglobulin and lyzozyme presence in urine?

Tubular dysfunction

(freely filtered, completlely reabsorbed)

GFR < 60 ml/min per 1.73 m² BSA

or

Albuminuria for >3 months

Hypovolemia

CHF

Cirrhosis

NSAIDs, ACEi, Vasopressors

                      Prerenal ARF                     Renal ARF

BUN/Cr ratio          

Specific gravity        

Osmolarity              

FENa                      

FE Urea                   

                Prerenal ARF                     Renal ARF

BUN/Cr ratio            >20:1                               <20:1

Specific gravity         High (>1.02)                Low (<1.01)

Osmolarity               High (>500mmol/kg)     Low

FENa                       <1%                            >2%

FE Urea                   <35%                          >35%

Ishcemia

Nephrotoxins

Refractory volume overload

Hyperkalemia

Metabolic acidosis

Uremia (w/ end organ damage)

BUN >100 gm/dL

Casts

RBC

Pigmented

WBC

Casts

RBC - Glomerulonephritis

Pigmented - ATN

WBC - Tubulointersitial nephritis (+/- eosinophils)

hCG

First detectable?

Doubles every 2 days to __ at __ weeks?

Doubles every 3 days to __?

Doubles every 4 days to __ at __trimester?

Plateaus at __ by early 2nd trimester?

hCG

First detectable? 7 days (10-50 mIU/mL)

Doubles every 2 days to _1200_ at _10_ weeks?

Doubles every 3 days to _6000?

Doubles every 4 days to 100,000 by end of 1st trimester?

Plateaus at _10,000_ by early 2nd trimester?

Multiple gestations

Eclampsia

Erythro Fetalis

Polyhydramnios

Transabdominal US - should detect IUP at __ hCG level?

Transvaginal US - should detect IUP at __ hCG level?

Transabdominal US - should detect IUP at _6000_ hCG level?

Transvaginal US - should detect IUP at _1400_ hCG level?

Risk of malignancy for complete moles?

For Partial moles?

Risk of malignancy for complete moles?

20%

For Partial moles?

<5%

Trisomy 18 (Edward)

AFP:

hCG:

uE:

Trisomy 18

AFP: Down

hCG: Down

uE: Down

Neural Tube Defect

AFP:

hCG:

uE:

Neural Tube Defect

AFP: Up

hCG: Normal

uE: Down

Down Syndrome

AFP:

hCG:

uE:

Dimeric inhibin A:

Down Syndrome

AFP: Down

hCG: Up

uE: Down

Dimeric inhibin A: Up

Effect of weight on MS-AFP?

Multiple gestations?

Maternal Diabetes?

Effect of weight on MS-AFP? Down (dilutional)

Multiple gestations? Up

Maternal Diabetes? Down

NTD

Omphalocele/gastroschisis

Renal anomalies

Saccryococcygeal teratoma

Cystric hygroma

Hydrops fetalis

Turners Syndrome

Bowel obstruction

Turner Syndrome

Twins

Wrong gestational age

Fetal Demise

Feto-maternal hemorrhage

Regular contractions

Cervical changes

< 37 weeks

L:S ratio - lung maturity?

Problems with L:S determination? ()

L:S ratio - lung maturity?

2:1

Problems with L:S determination? ()

Diabetes Mellitus - ratio not reliable

Meconium - False decrease

Blood- normalizes to 1.5:1

Flourescence Polarization- Fetal Lung Maturity

< ? : Mature?

> ? : Immature?

Flourescence Polarization- Fetal Lung Maturity

< 260 : Mature

> 290 : Immature

Pregnancy Analyte Changes

Albumin:

Calcium:

Creatinine:

Fibrinogen:

Albumin:

BUN:

Urine protein:

Amylase:

Hgb/Hct:

Pregnancy Analyte Changes

Albumin: Down (1gm/dL)

Calcium: Down (10%)

Creatinine: Down (0.3 mg/dL)

Fibrinogen: Up (1-2 g/L)

Albumin: Down (0.5-1 g/dL)

BUN: Down (50%)

Urine protein: Up (Double)

Amylase: Up (50-100%)

Hgb/Hct: Down (1.5-2 g/dL)

DVT risk

Antepartum?

Postpartum?

PE risk?

DVT risk

Antepartum? 1/2000

Postpartum? 1/700

PE risk? 1/2500

Ameliorated/Aggravated by Pregnancy?

Rheumatoid Arthritis

Graves Disease

SLE

Myastenia Gravis

Ameliorated/Aggravated by Pregnancy?

Rheumatoid Arthritis : Better

Graves Disease: Better

SLE: Worse

Myastenia Gravis: Post partum exacerbation

SS-A, SS-B (Ro and La)

"Baby RoLa"

Post partum Hypopituitarism

(Enlarged Pituitary, Decreased blood flow)

1/10,000

3rd Trimester

30% fatality

Microvesicular steatosis

3rd trimestery

Alk phos up

Bili up (direct conjugated)

Bile acids up

When drug amount leaving body equals amount entering

(MC after 5 half lives)

([] lowest before, and highest shortly after administration)

V_d = D/C

D: Dose

C: Plasma concentration

                 Half Life        Detectable     Metabolite

Cocaine

Heroin

Amphetamines

PCP

Cannabis

                 Half Life        Detectable     Metabolite

Cocaine           1h                1-3d  benzyl ecgonine      methyl ester

Heroin              3 min            3d    6-acetyl morphine

Amphetamines 30 min         3d    norep, phenylacetone

PCP                30 min             3d    hydroxy & glucoron

Cannabis       8h              weeks   9-THC-COOH

Blocks  catecholamine re-uptake

(horizontal nystagmus)

Ethanol                            Contrast

Ethylene glycol                  Hypermagnesemia

Methanol

Isopropyl alcohol

Propylene glycol

Glycerol

Acetone

Mannitol

Ethylene glycol metabolized to glycolic acid

Glycolic acid (CNS manifestations)

Oxalate via alcohol dehydrogenase - Ca oxalate (envelope shaped) 

 Methanol

Formaldehyde

Formic acid (alcohol dehydrogenase)

---- Ocular toxicity, AG acidosis, Osmolal Gap

Isopropyl alcohol

Acetone

Osmolal Gap, Ketonemia/uria

NO: acidosis, increased anion gap

Delays development of increased AG metabolic acidosis

Thus, only clue to Dx may be elevated osmolal gap. 

Inhibits enzymes (sulfhydryl groups)

Toxic to mitochondria

S-ALA-dehydratase

Ferrochelatase

(Accumulation of protoporphyrin (FEP). FEP binds to zinc leading to ZPP 

Difference between pulse ox and co-oximetry (reflects level of Hb-CO)

[pulse ox may overestimate oxygen saturation]

Proportional

6hours- room air

1 hour - 100% O2

1: discomfort

2: progressive liver injury

3: fulminant hepatic failure

4: resolution (recovery, transplant, death)

1.Glucoronide or sulfate (nontoxic metabolites)

2.P₄₅₀ system (small amount) - NAPQI metabolite [normally detoxified by glutathione, but in excess gluthathion overwhelmed]

NAQPI 

(n-acetyl-p-benzoquinoneimine)

Type of hepatic necrosis?

Centrilobular (zone 3)

Periportal sparing

Tx: N acetyl cystein ; Mucomyst- promotes conjugation pathways

Inhibits cytochrome A3

Uncouples electron transport

Decreased oxygen dependent metabolism

Results: AG metabolic acidosis

Cherry red color (oxygen in blood)

CN rapid metabolism to Thiocyanate

Lactate elevated always

AG metabolic acidosis

Elevated glucose (decreased usage)

Tx: Na nitrite,amyl nitrite (methHb formation that binds cyanide)

1. respiratory alkalosis (stimulation medulla)

2.metabolic acidosis (ox phos uncoupling)

Triphasic: 1.respiratory hyperventilation 2.metabolic compensation (12-24h) 3.increased AG metabolic acidosis

Lab testing of elemental mercury?

Of Organic mercury?

Lab testing of elemental mercury?

-24 hour urine collection

Of Organic mercury?

-Whole blood, hair (not in urine)

36 hours

(draw level 10 days, 10 hours after last dose)

B-48

A-1

C

E

"BACE"

B-100

C

E

B-100

E

A-1

C

E

HDL function?

LDL function

HDL: Scavenges cholesterol from periphery to liver

LDL: Transports cholesterol to somatic cells

Lipid Disorders - Increased?

I

II

III

IV

V

Lipid Disorders - Increased?

I - chylomicrons

II - LDL

III - IDL

IV - VLDL

V - VLDL and chylomicrons (I + IV) 

protein ratio >0.5

LDH ratio >0.6 and LDH >200

Some other ancillary tests:

specific gravity (>1.01 implies exudate

protein >3g/dL

cholesterol >45 mg/dL 

bilirubin ratio >0.6

vitreous chemistry patterns is most consistent with decomposition?

decreased sodium, decreased chloride, increased potassium