Clin Lab exam 2

How to calculate anion gap

Na - (CL + HCO3)

difference between cations and anions

In what clinical state would you see increased albumin?

dehydration

in what clinical state would you see decreased albumin

liver disease, renal disease, malnutrition, malabsorption disorders (churns, whipples, sprue), muscle-eating disease

albumin

highest concentration in plasma

maintains appropriate fluid balance in tissues

functions as carrier protein

produced and secreted by liver

pre-albumin

carrier protein for thyroid hormones T3 and T4

transports vit A when complexed with retinol binding protein

sensitive marker of inadequate dietary protein intake

dec in hepatic diseases, acute inflammatory responses, tissue necrosis

AAT

majority component of alpha-1 globulin

acute-phase reactant

neutralizes elastase that damages structural proteins (released as part of immune process)

AFP

alpha-1 globulin

protects fetus from attack by mothers immune system

prenatal screening routinely performed between 15th and 20th week of gestation (protein freely crosses placenta)- triple screen (AFP, estradiol, HCG)

What is the clinical significance of alpha-1 antitrypsin? (AAT)

deficiency associated with sever, degenerative emphysematous pulmonary disease

a cause of emphysema in young people (20-40) who DO NOT smoke

high AFP during pregnancy

possible open neural tube defect in fetus

atresia of GI tract

fetal distress

Low afp in pregnancy

inc risk of downs syndrome and trisomy 18

high AFP not pregnant

liver cancer and adult gonadal cancers (testicular and ovarian)

tumor marker for these cancers

What is another setting AFP might be utilized besides pregnancy?

tumor marker for adult gonadal cancers

Acute-phase reactant

inc in response to trauma / inflammation to help prevent loss of hemoglobin from damaged RBCs

haptoglobnin

alpha-2 globulin; acute phase reactant

starts in liver

synthesized in hepatocytes and cells of reticuloendothelial (RE) system

binds free Hgb (RE removes complex)

prevents loss of Hgb and iron from kidneys

haptoglobin (alpha-2 globulin) is considered an acute phase reactant. describe a scenario it would be elevated.

infection or inflammation

ceruloplasmin

alpha-2 globulin

copper-containing protein with enzymatic activity (>90% total serum copper in it)

acute phase reactant

ceruloplasmin clinical significance; low levels

low levels seen in Wilson’s disease- inherited disease where copper is deposited in the liver, brain, and skin cause brain and neurologic damage (Kayser fleischer rings)

alpha-2 macroglobulin

alpha-2 globulin

large protein synthesized by hepatocytes

found in intravascular spaces

inhibit variety of protease enzymes (trypsin, Pepsin, plasmin)

elevated in renal disease

transferrin

synthesized by liver

major component of beta globulin fraction

transport iron and prevent loss

transferrin main function

transport iron and prevent loss of iron through the kidneys

transferrin clinical significance

decreased level in liver disease (dec synthesis)

TBIC- increase in iron deficiency anemia

What type of reactants are complement proteins?

proteins involved in immune and inflammatory responses; acute phase reactant

circulate blood as non-function precursors- activated when antigen-antibody (Ag-Ab) complexes are present (lysis of those cells);

opsonization- coat bacterial cells and increase likelihood of phagocytosis

what clinical scenarios would complement proteins be increased or decreased?

inc- inflammatory states

dec- systemic lupus erthematosis

fibrinogen

synthesized in liver

acute phase reactant

What is the function of fibrinogen?

formation of fibrin clot when activated by thrombin (removed during clotting process so not seen in serum)

clinical significance of dec fibrinogen?

severe liver disease

DIC (disseminated intravascular coagulation)

C-reactive protein (CRP)

acute phase reactant- one of the first inc in response to inflammation

non specific

can be used in place of ESR

commonly assayed as part of risk assessment for cardiovascular disease; indicates chronic inflammatory process ongoing in vascular system that enhances formation of atherosclerotic plaques, esp in coronary arteries

when is CRP elevated

significantly elevated in acute rheumatic fever, MI, viral infections, bacterial infections, rheumatoid arthritis

immunoglobulins synthesized by

plasma cells (B lymphocytes)

which is most abundant of immunoglobulins

IgG

elevated IgA levels

liver disease

autoimmune diseases

infections

elevated IgD

liver disease

infections

connective-tissue disorders

multiple myeloma

elevated IgE

asthma

allergic rhinitis

parasitic infections

elevated IgG

(infection is Gone)

liver disease

infecitons

collagen disease

multiple myeloma

elevated IgM

(need More first)

first to appear in immune response to foreign antigen

waldenstron’s macroglobunlinemia/lymphoplasmacytic lymphoma)

monoclonal gammopathies

dec immunoglobulins

inherited immunodeficiency disorders (faulty plasma cell function)

describe how there may be excessive protein loss from each system?

renal- diseases that damage glomerulus of nephron (proteinuria)- nephrotic syndrome

gi- protein leakage into GI tract due to protein-losing enteropathy (PLE)

skin- severe skin diseases- extensive burns

blood- bleeding- large loss of proteins with the blood

liver is the site of all ______ protein synthesis

non-immune

(all proteins synthesized in liver except gamma globulins)

describe the levels of all proteins in state of liver disease

inc: gamma globulin proteins

dec: plasma protein, albumin

what is the most commonly used screening test for serum protein abnormalities? what are the five protein fractions identified?

serum protein electrophoresis- separating proteins based on electric charge properties

albumin

alpha 1 globulin

alpha 2 globulin

beta

gamma

AAT deficiency SPE

dec alpha-1

chronic inflammation SPE

elevated alpha 1, alpha 2, beta, and gamma

nephrotic syndrome SPE

alpha 2 elevated

albumin dec / lost in urine

severe cirrhosis SPE

dec albumin and alpha 2

inc beta and gamma

glycolysis

breakdown/oxidation of glucose to be used as energy

glycogenesis

buildup/glucose converted to glycogen for storage

glygogenolysis

breakdown/glycogen converted to glucose from storage

gluconeogenesis

build up/ new glucose formed from amino acids ( when there is nothing left in glycogen stores)

what role do insulin and glucagon play in control of plasma glucose

insulin- dec plasma glucose, bring down blood sugar, promote glycogenesis and inc cellular uptake

glucagon- inc plasma glucose in times of need, stimulate glycogenolysis and gluconeogenesis

diagnostic criteria for diabetes

fasting plasma glucose 126 mg/dl or more

symptoms and random plasma glucose 200 mg/dl or more

hemoglobin A1C 6.5% or more

2 hr plasma glucose 200 mg/dl or more during oral glucose tolerance test

one of these confirmed on repeated testing on different day

glucosuria

glucose in urine

generally when blood glucose level exceeds about 160-180 mg/dl

epinephrine _____ plasma glucose

increases

GH, ACTH, Cortisol, thyroid hormones ______ plasma glucose

increases

symptoms of hyperglycemia

nausea/vomiting, malaise, diarrhea

high and dry

symptoms of hypoglycemia

nausea, trembling/sweating, rapid pulses, lightheadedness, CNS symptoms (altered mental status)

cold and clammy gets them candy

type 1 DM

insulin dependent

caused by autoimmune destruction of pancreatic beta cells → absence of insulin production

pts usually less than 20 yrs

labs: hyperglycemia, hyperkalemia, glucose and ketones in urine

type 2 DM

non-insulin dependent

caused by insulin resistance - insulin levels high but not effective at maintaining normal glucose levels

insulin produced by beta islet cells, but target cells unresponsive; insulin levels increased, however, target cells are resistant to the insulin

dec number of insulin receptors caused by obesity receptors destroyed by antibodies

genetically determined insulin receptor insensitivity

patients usually older than 40 and obese

majority of DM

beta cells produce ______ and alpha cells produce _______

insulin, glucagon

DKA (diabetic ketoacidosis)

type 1 diabetics (type 2 has enough insulin to prevent accumulation of ketones)

missed insulin dose causes:

• inc fat breakdown and fatty acid metabolism → inc ketones → metabolic acidosis (high anion gap) → hyperkalemia

• hyperglycemia (500 msg/dl) → osmotic diuresis → dehydration

• relative increase in glucagon which enhances problems

insulin dose is taken but insufficient for new stress or infection

What is the hallmark for DKA?

positive plasma ketone level (urine ketones not specific, may be detected in healthy fasting people)

lab diagnosis of DKA

positive plasma ketone level

hyperglycemia

Hgb A1C reflect glucose control over how long?

8-12 weeks, 3 months

pre diabetic A1C range

5.6-6.4 %

diabetic A1c range

6.5% or more

normal A1c range

4.8-5.5%

What test is most appropriate gestational diabetes?

1 hour oral GTT (50 mg glucose)- routine screening beginning of 3rd trimester (24-28 weeks)- confirmed with 3 hr

3 hr oral GTT (100 mg glucose)

• 4 blood draws- 0 hrs, 1 hr, 2 hr, 3 hr

• if at least 2 out of 4 samples at or above cutoff values, test is positive

oral glucose tolerance test

unrestricted diet 3 days before (at least 150 gm carb daily)

10-16 hour fast before test (may drink water)

oral glucose ingested within 5 min

patient must remain seated until 2 hour blood sample drawn

specimen must be frozen or analyzed within 4 hours to determine plasma glucose

microalbumin testing

very sensitive

reveals earliest, reversible renal disease

albuminuria may precede other signs of renal disease by 10-15 years: slow progression of microalbuminuria → macroalbuminuria

What is role of microalbuminuria testing in patients with diabetes? what findings become more concerning?

reveal early, reversible renal disease (high blood sugar damage blood vessels in kidneys)

- microalbuminuria- 30-300 mg/day

macroalbuminuria- more than 300 mg/day - concerning

which electrolytes are inside cell?

K and HCO3

which electrolytes are outside cell

Na and Cl

what regulates Na

kidneys - ADH and aldosterone

what regulates K

kidneys- proximal tubules

aldosterone regulates Na/k exchange in kidney

what regulates Cl

aldosterone- excess sweating stimulates aldosterone which conserves Na and Cl

kidneys

what regulates HCO3

kidneys

aldosterone

Na retaining hormone

increases Na and water with K loss

manages Na/K exchange in kidneys

hyponatremia

ratio between Na and H20; H20 greater than Na

hypo hypo- low H20, lower Na

normo hypo- high H20, normal Na (looks dilute)

hyper hypo- higher H20, high Na

hypovolemic hyponatremia

(low H20, lower Na)

water and sodium both lost from body, but sodium loss is greater

causes: loss of fluid (GI, burns) with hypotonic fluid replacement

thiazide diuretics- inc Na and K loss

K depletion in cells- causes Na movement into cells

aldosterone deficient - inc Na and water loss

normovolemic hyponatremia

(high H20, normal Na)

total body water increases, but body’s sodium content stays the same

causes: SIADH- body hangs on to water, diluting Na

severe hyperglycemia (polyuria)- water moves into plasma to normalize osmolality

polydipsia- inc thirst

diuretics

hypothyroidism

hypervolemic hyponatremia

(higher H20, high Na)

both sodium and water content increase, but water gain is greater

causes: CHF
hepatic cirrhosis

overhydration

nephrotic syndrome

renal failure - inability to excrete water

hyponatremia symptoms

nausea

generalized weakness

mental confusion

hypernatremia symptoms

tremors

irritability

ataxia- loss of coordinated muscle movement

confusion

coma

hypovolemic hypernatremia

(lower H20, low Na)

lose more H20 than Na

most common cause of hypernatremia

causes: dehydration

profuse sweating

vomiting or diarrhea

normovolemic hypernatremia

low H20, normal Na

causes: skin/lung loss

DI- water loss with Na retention

hypervolemic hypernatremia

high H20, higher Na

causes: hypertonic saline treatment

hyperaldosteronism

causes of hypokalemia

diuretics (most common)

decreased dietary intake

excessive insulin

alkalosis

hypomagnesemia - enhances aldosterone secretion

hyperaldosteronism

causes of hyperkalemia

excess intake - diet

acidosis

insulin deficiency- loss of cellular K+

drugs (heparin, digoxin, cyclosporine)

Ace inhibitors, K sparing diuretics

dec excretion- renal failure, hypoaldosteronism

loop and thiazide diuretics

inc Na deliver to distal segment of distal tubule → inc K loss

this stimulates aldosterone-sensitive Na pump to inc Na reabsorption in exchange for K and H (lost in urine)

What other electrolyte does Cl parallel?

Na

hyperchloremia

parallels hypernatremia

causes: hyperventilation (respiratory alkalosis)

dehydration

excess loss of bicarb (gi loss / diarrhea leading to metabolic acidosis, rental tubular acidosis)

hypochloremia

parallels hyponatremia

causes: prolonged vomiting

metabolic alkalosis

pylonephritis - sodium losing renal disease

what is considered an indirect measure of HCO3 anion

CO2

Low AG associated with

multiple myeloma

instrument error

(rare)

normal blood pH

7.35-7.45

volatile acids

derived from CO2 (can be exhaled)

respiration allows volatile acid/CO2 to be removed by lungs and the remaining byproduct is H20 (neutral)

acid base balance is maintained by

lungs and kidneys

bicarb buffer system formula

CO2 + H2O → H2CO3 → HCO3- + H+

nonvolatile sources

derived from sources other than CO2 (can’t be exhaled)

keto acids, lactic acid, sulfur and phosphorus containing compounds

excreted by kidneys

values are more accurate from _____ than ______

arterial blood than venous blood

metabolic acidosis

decrease in plasma HCO3-, dec pH, kidney

dec bicarb due to inc accumulation of nonvolatile acids or loss of bicarb from kidney or GI tract (diarrhea, vomiting)