Chem ppt flashcards, Unit 4



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Ketostix give a positive result in how many seconds with specimens containing how much acetoacetate in the sample?

15s , 50mg/L

What test tests for β-hydroxybutyrate?

DiaScreen 1K


What is the first step in the DiaScreen 1K test?

β-hydroxybutyrate in the presence of NAD is converted by β-hydroxybutyrate dehydrogenase to acetoacetate, producing reduced NADH.

The second step in the DiaScreen 1K test once NADH is produced is?

Diaphorase catalyzes the reduction of nitroblue tetrazolium (NBT) by NADH to produce a purple compound, and its absorbance is read in a special meter that provides a digital readout.

How is HbA1c formed?

the condensation of glucose with the N-terminal valine residue of each β-chain of HbA to form an unstable Schiff base that may dissociate to form a stable ketoamine.

True or false

The rate of HbA1c formation is directly proportional to the concentration of glucose in the body.



True

How far in the past does the HbA1c assay detect glucose values?

HbA1c concentration represents integrated values for glucose over the preceding 8-12 weeks.

An HbA1c value of ≥ 6.5% is considered to be the decision point used for the diagnosis of?

Diabetes

What HbA1c value range indicates individuals at high risk of developing diabetes?

from 5.7% to 6.4%

What is the “normal” reference interval for HbA1c?

4%-5.6%

True or false

HBA1c is accepted to be an alternative to glucose for screening for diabetes.



True

What test is is firmly established as an index of long-term blood glucose concentration and a measure of the risk for developing microvascular complications in patients with diabetes.

HbA1c

In patients without diabetes, how is HbA1c used?

HBA1c is directly related to risk of cardiovascular disease

How is HbA1c used to monitor patients who are compliant to the diabetic lifestyle, diet, exercise etc.?

It is recommended that HbA1c should be routinely monitored at least every 6 months in patients meeting treatment goals and who have stable glycemic control.

What are the three general methods for HbA1c determination?

Methods based on Charge differences.

Methods based on structural differences.

Methods based on chemical analysis.


What are the HbA1c methods based on charge differences?

Ion Exchange Chromatography

HPLC


Electrophoresis

Isoelectric focusing



What are the HbA1c methods based on structural differences?

Affinity Chromatography

Immunoassays



What are the HbA1c methods based on chemical analysis?

Photometry

spectrophotometry



Is fasting required for the HbA1c test?

No

What type of tube/anticoagulant should be used for the HbA1c test?

Lavender EDTA, Gray oxalate or fluoride

Fructosamine is?

the generic name for plasma protein ketoamines, specifically glycated serum albumin.

How far in the past does glycated albumin measure glucose control?

2-3 weeks

When is glycated albumin most useful?

Useful in conditions where HBA1c is of little value, such as I patients with hemoglobin variants that are associated with decreased erythrocyte life span.

What are three test methods used to measure glycated albumin?

1. Affinity Chromatography

2. High Performance Liquid Chromatography



(HPLC)

3. Photometric and Spectrophotometry



What refers to an excretion rate of albumin greater than normal but less than that detectable by routine dipsticks methods?

High albuminuria (formerly known as microalbuminuria).

What is the excretion rate?

20 to 200 µg/min (30 to 300 mg/24hours

What does a UAE rate of greater than 200µg/min indicate?

Overt diabetic nephropathy

What does urinary albumin excretion precede and is highly indicative of?

  1. Diabetic nephropathy

  2. End-stage renal disease

  3. Cardiovascular mortality

Total mortality in patients with diabetes

What else can UAE indicate?

It identifies a group of people without diabetes who are at risk for coronary artery disease

What physiological factors can increase UAE?

  1. Exercise

Posture and diuresis

When should sample for UAE not be collected?

  1. After exertion

  2. In the presence of infection (UTI)

  3. During acute illness

  4. Immediately after surgery

After an acute fluid load

What are some examples of acceptable specimens?

  1. 24 hour collection

  2. Overnight (8-12 hours times)

  3. 1-2 hour timed collection

First morning sample

At what temperature is urine stored and for how long is it stbale?

Urine should be stored at 4 degrees Celsius after collection. It is stable for 1 week at 4 degrees Celsius and for at least 5 months at -80 degrees Celsius. Urine should be stored at 4 degrees Celsius after collection. It is stable for 1 week at 4 degrees Celsius and for at least 5 months at -80 degrees Celsius.

At what temperature does albumin concentration decrease by 0.27 % per day?

-20 degrees celsius

What temperature should refrigerated urine samples be allowed to reach before analysis?

10 degrees Celsius

How many specimens should be assayed and why?

At least 3 separate specimens, collected on different days, should be assayed because of high intraindividual variation and diurnal variation (50% to 100% higher during the day)

What does diagnosis require?

Increased UAE in at least 2 of 3 test measured within a 3-6 month period

What testing methods are used?

  1. Test strips are semi-quantitative assays used for screening

Quantitative methods

What are some examples of quantitative methods used to screen UAE?

  1. RIA

  2. ELISA

  3. Radial Immunodiffusion

Immunoturbidimetry

What are the two most common cardiovascular disorders that rely on a biochemical diagnosis?

  1. Acute ischemic disease (acute myocardial infarction)

Heart failure (congestive heart failure)

What are the measurement of cardiac biomarkers useful in diagnosing and detecting?

  1. Cardiac disease

  2. Cardiac disorders

  3. Detecting the risk of developing cardiac disorders

  4. Monitoring the disorder

Predicting the response of a disorder to a treatment

What is the most serious form of ischemic disease?

Acute myocardial infarction (AMI)

What is an acute myocardial infarction?

It is an acute infarction (obstruction of circulation) of the heart muscle occurring during the period when circulation to a region of the heart is obstructed and necrosis is occurring

When does this occur?

It occurs when there is an imbalance between supply and demand for oxygen in the myocardium

What is the result when this happens?

This can result in injury and to eventual death of muscle cells. When blood supply is blocked for more than a few minutes, most of the muscle cells die.

What is the condition marked by severe pain in the chest, often also spreading to the shoulders, arms and neck caused by an inadequate blood supply to the heart?

Angina

What is an angina that occurs unpredictable or suddenly increased in severity of frequency?

Unstable angina

What is a sudden cardiac disorder that varies from angina to unstable angina and to myocardial infarction?

Acute coronary syndrome

What is the weight of the average human heart?

325 grams in men and 275 grams in women

What is the sac that encloses the heart?

Pericardium

What are the 3 layers of the cardiac wall?

  1. Epicardium (outermost layer where coronary arteries are found)

  2. Middle layer

  3. Endocardium (innermost layer most susceptible to myocardial ischemia)




What are the 4 chambers of the heart?

Upper chambers (right and left atria)

Lower chambers (right and left ventricles)



A cardiac cycle consists of what two intervals?

Systolic and diastolic

What is systolic pressure?

The blood pressure in the aorta is about 120 mm Hg

What is diastolic pressure?

The blood pressure falls to about 70 mm Hg

What is an electrocardiogram (ECG)?

It records changes in electrical potential and is a graphic tracing of the variation in electrical potential caused by the excitation of the heart muscles.

What is an ECG used to identify?

Used to identify the anatomic, metabolic, ionic, and hemodynamic changes in the heart

What are an ECG’s three major components

  1. Atrial depolarization (p wave)

  2. Ventricular depolarization (QRS complex)

Repolarization (ST segment and T wave)

What is acute coronary syndrome?

Includes individuals who have a variety of forms of unstable ischemic heart disease

What is the major cause of acute coronary syndrome?

Athersosclerosis

What is atherosclerosis?

A diseased caused by plaque (a deposit of fatty material) formed in the inner lining of the coronary arteries that feed the surface of the heart, contributing to significant narrowing of the artery’s lumen.

Atherosclerosis, the abnormal blood flow through the narrowing of an artery is caused by what yellowish substance?

Atherosclerotic Plaque

Detection of rise and/or fall of cardiac biomarkers (preferably troponin) above the 99th % of the upper reference limit, together with evidence of ischemic symptoms with at least one of the fallowing symptoms of ECG changes of ischemia changes or new left bundle branch block, development of pathologic Q waves on the ECG, identification of an intracoronary thrombus by angiography or autopsy is criteria for the definition of what?

Myocardial Infarction

4 cardiac markers for the diagnosis of acute myocardial infarction are?

AST, SGOT - aspartate aminotransferase

LD - lactate dehydrogenase

CK - total creatine kinase

a-hydroxybutyrate



A condition in which the heart has lost the ability to pump enough blood to the body’s tissue?

Congestive Heart Failure (CHF)

As a result to CHF, the _____ may respond by causing the body to retain fluid (water) and salt.

kidneys

A common cause of CHF; a disease of the arteries that supply blood and oxygen to the heart causes decreased blood flow to the heart muscles. The heart becomes starved for oxygen and nutrients if the arteries become blocked or severed narrowed. This disease is known as?

Coronary artery disease (CAD)

A common cause of CHF include damage to the heart muscle from causes other than artery blood flow problems such as from infections, alcohol or drug abuse is known as?

Cardiomyopathy

These are substances that are released onto the blood when the heart is damaged or stressed.

Cardiac Biomarkers

Measurements of cardiac biomarkers are used to help diagnose ___ ____ ____and ___ ___, conditions associated with insufficient blood flow to the heart as well as CHF.

acute coronary syndrome (ACS)

and


cardiac ischemia

These are specific proteins found in cardiac muscles and are measured in the diagnosis of myocardial infarction.

cTns

Three troponin subunits form a complex that regulate the interaction of actin and myosin and thus regulate cardiac contractions are?

Troponin T (the tropomyosin-binding component)

Troponin I (The inhibitory component)

Troponin C (the calcium-binding component)


Cardiac troponin __ and Cardiac troponin __ are the two main types of troponin used as cardiac biomarkers.

Cardiac troponin I (cTnI)

and


Cardiac troponin T (cTnT)

Trponins are localized primarily (94%-97%) in the ____ with smaller cytoplasmic fraction.

myofibrils

In general, what is the technique of choice for measuring cTns?

Immunoassay

The laboratory should perform biomarkers testing with a maximum turnaround time (TAT) of how long?

1 hour 30 minutes

What term is defines as the time from blood collection to the reporting of results to the provider?

Turnaround time (TAT)

What type of blood specimen appears to be the optimal specimen for rapid processing and testing?

Anticoagulated whole blood or plasma

What two blood tube collection additives interfere with troponin antibody-binding affinity?

EDTA and Heparin

This type of cardiac testing is detected by a 32-amino acid polypeptide secreted by the ventricles of the heart in response to excessive stretching of heart muscle cells (cardiomyocytes). The release of this test is modulated by calcium ions.

Brain Natriuretic Peptide (BNP)

The 3 major circulating forms of BNP are?

  1. NT-pro BNP (N-terminal protion or fragment of proBNP)

  2. proBNP

  3. BNP (C-terminal part of proBNP and the physiological active hormone




What does a normal level of either BNP or NT-proBNP rule out in am emergency setting?

Acute heart failure

True or False

An elevated BNP or NT-proBNP should never be used to rule in acute or chronic heart failure in emergency settings due to lack of specificity



True


What can be used for screening and prognosis of heart failure?

Either BNP or NT-proBNP

BNP or NTproBNP are typically increased in what kind of patients?

Patients with left ventricular dysfunction, with or without symptoms

BNP accurately reflects what?

Current ventricular status

What is the half-life of BNP?

20 minutes

What is the half life of NT-proBNP?

1-2 hours

How are the concentrations of BNP and NT-proBNP measured?

By immunoassays

What is the acceptable specimen used for BNP?

EDTA-anticoagulated whole blood or plasma in plastic blood collection tube

What is the acceptable specimen used for NT-proBNP

Serum, heparin-plasma, EDTA plasma collected in either glass or plastic

Where is CK enzyme present? (3)

Heart muscle, skeletal muscle and the brain

Name the 3 isoemzymes of CK

CK1 or CKBB

CK2 or CKMB

CK3 of CKBB

CK-Mt


Which CK isoenzyme is the dominant form in the brain and smooth muscle?

CK1 or CKBB

Which CK isoenzyme is sometimes called the cardiac isoenzyme because 10%- 20% of total CK activity in myocardium is from CK-MB?

CK2 or CKMB

Which CK isoenzyme is predominant in both heart and skeletal muscle?

CK3 or CKMM

What is CK-Mt

Mitochondrial isoenzyme

What is C-reactive protein?

An acute phase reactant initially developed to evaluate patients with infection

What does it mean when concentrations of C-reactive protein fall below those seen in infection but above healthy values?

They are shown as biomarkers of arteriosclerotic process

What is an oxygen binding protein of cardiac and skeletal muscle?

Myoglobin

Myoglobin levels increase before CK2 after what?

AMI

(Increases/decreases) in serum myoglobin occur after trauma to skeletal or cardiac muscle as in crush injuries or AMI

Increases

Why are false-negative results of myoglobin seen in patients after a few hours?

Because increases of serum concentrations of myoglobin are cleared rapidly

True or False

Kidneys play a central role in homeostatic mechanisms



True

Fill in the blank:

Kidneys filter the _______ and excrete the end products of the body metabolism in the form of ________.



Blood; Urine

The kidneys regulate the concentrations of which ions?

Hydrogen, sodium, potassium, phosphate, and other ions in the ECF

True or False?

Kidneys do not function to produce hormones



False

What is the functional unit of the kidney?

The nephron

Name all the parts of the nephron

Glomerulus, proximal tubule, loop of Henle, distal tubule, and collecting duct

What is the outer region of the kidney called?

Cortex

What is the inner region of the kidney called?

Medulla

Where is the glomerular capillary network formed?

On the basement membrane

What does Pars convolute become?

Pars recta

What does the collecting ducts form?

Ducts of Bellini

What does the ducts of Bellini drain into?

The renal calyx

What is glomerulus formed by?

Specialized network of capillaries on basement membrane.

What is the Juxtaglomerular Apparatus?

Area of specialization at area of loop of Henle and Bowman's capsule

What does it do?

Maintains systemic blood pressure by regulating blood volume and sodium concentration

What does it generate?

Generates angiotensin

How does vasoconstriction work?

acts to increase release of antidiuretic hormone

What do Anterior and posterior renal artery divide into ?

arterioles and then capillaries

What do capillaries form?

efferent arteriole

Efferent arteriole merges with what?

renal venules to form renal veins

Renal veins emerge into what?

inferior vena cava

Kidneys receive how much of cardiac output in adults?

about 25%

What are the 3 functions of the kidneys?

Excretion, Homeostatic regulation, Endocrine

Urine passes from kidneys to?

Ureters, to bladder, exits urethra

Characteristics of healthy urine?

sterile, clear, amber, slightly acidic

Urination (or micturition) is adequate at?

about 500 mL per day

Oliguria (<400 ml/day) is?

decrease in the normal daily urine output

What does oliguria result from?

commonly accompanies states of dehydration such as vomiting, diarrhea, perspiration or severe burns

What is Anuria?

Absence of urine

What does anuria result from?

results from serious damage to the kidneys or from a decrease in the flow of blood to the kidneys

Polyuria is what?

increase in the normal daily urine output, (>3,000 ml/day)

What causes polyuria?

seen in diabetes mellitus and diabetes insipidus

induced with diuretics, caffeine or alcohol consumption



What is Nocturia?

increase in the excretion of urine at night

What types of homeostasis is regulated in kidneys?

Electrolyte and water.

How is electrolyte homeostasis maintained?

Reabsorption in proximal convoluted tubule

Bicarbonate, phosphate, high-threshold substances, uric acid



How is water homeostasis maintained?

70% reabsorbed in proximal tubule

5% in loop of Henle

10% in distal tubule

Remainder in collecting ducts



What hormones are produced?

Erythropoietin, Prostaglandins and thromboxanes, Renin, and 1,25(OH2) vitamin D3

Secondary endocrine function is what?

(site of action for hormones produced or activated elsewhere)

Three physiological functions of kidneys?

Glomerular Filtration Rate (GFR), Renal Blood Flow

Glomerular Permeability



What does GFR measure?

functional capacity of the kidneys and indicative of the number of functioning nephrons.

What is useful about measuring GFR?

targeting treatment, monitoring progression, predicting when renal replacement therapy (RRT) will be required, and as a guide to dosage of drugs excreted by the kidneys to prevent potential drug toxicity.

The renal clearance of a substance is defined as what?

as "the volume of plasma from which the substance is completely cleared by the kidneys per unit of time".

For a substance(s) or marker(s) to be used to measure renal clearance, it must be what 7 things?

1. In stable concentration in the plasma

2. Physiologically inert

3. Freely filtered at the glomerulus

4. Neither secreted

5. Neither reabsorbed

6. Neither synthesized

7. Not metabolized by the kidney


What is the concept of the renal clearance of a substance?

Clearance (ml/min)

= U/P x V (mL/min) x 1.73/A




What are U,P, V, 1.73, and A stand for?

U= concentration of the substance in urine

P = concentration of substance in plasma

(blood)

V = total volume of urine excreted in 24 hrs



converted to mL/min

1.73 = body surface area in square meters

A = body surface of patient obtained from

patient’s height and weight (nomogram)




What markers have been used to estimate clearance?

A variety of endogenous and exogenous markers.

Endogenous markers:

Creatinine concentration

Low–molecular weight proteins (Cystatin C)

Exogenous markers:

Inulin


Iohexol

Radiopharmaceuticals

51Cr-ethylenediaminetetraacetic acid (EDTA)

99mTc-diethylenetriaminepentaacetic acid

(DTPA)

125 I-iothalamate




What urinary protein loss is defined?

Increased urinary protein loss (proteinuria) results from any increase in the filtered load, increased circulating concentration of low molecular weight proteins, or decrease in reabsorptive capacity

How is the normal urinary total protein loss?

It is less than 150 mg /24 hours which is mostly albumin (50% to 60%)

What primary part is the predominant protein in urine in the majority of kidney diseases and is accurately and specifically measured using immunoassay techniques?

Albumin

How is progression of kidney disease leading to loss of function and ultimately to kidney failure?

These are:

Early inflammation

Accumulation and deposition of extracellular matrix

Tubulointerstitial fibrosis

Tubular atrophy

Glomerulosclerosis (scarring)




How many parts pathophysiology of kidney disease are?

Diagnosis and screening for kidney disease

Urinalysis

Proteinuria

Hematuria

a symptoms or physical sign

systemic disease with the known renal involvement like diabetes mellitus



What is the definition of Acute kidney injury (AKI)?

1. Increase of plasma creatinine by ≥ 0.3 mg/dL

(26 µmol/L) within 48 hours

2. Increase in plasma creatinine to ≥ 1.5 times

baseline, which is known or presumed to have

occurred within the prior 7 days

3. Reduction in urine output (documented oliguria



< 0.5 mL/kg/hr for more than 6 hours


How Chronic kidney disease (CKD) is defined?


Is defined as abnormalities of kidney structure or function, present for more than 3 months with implications for health

What markers used to identify CKD?

These are plasma creatinine, estimated GFR and measured creatinine.

Lowering blood pressure and reduction of proteinuria have been shown to decrease the progression of CKD



What is sevenfold to tenfold greater in patients with CKD?

The incidence of cardiovascular disease

What is characterized as elevated total or low-density lipoprotein (LDL) cholesterol levels, and elevated triglycerides.


It is Dyslipidemia in CKD

What is is also affected in CKD, leading to "adynamic" bone diseases.


Calcium and phosphate metabolism

How Adynamic bone is defined?

bone is associated with low PTH concentration, abnormal calcium balance, hyperphosphatemia, acidosis and the use of high doses of vitamin D analogs.Due to the predominant loss of peritubular fibroblast (specialized cells that produce collagen) within the renal cortex that synthesize erythropoietin, thus causing anemia

How the classic signs of uremia?

The symptoms are progressive weakness and easy fatigue, loss of appetite followed by nausea and vomiting, muscle wasting, tremors, abnormal mental function, frequent but shallow respirations and metabolic acidosis.


What are the most characteristic laboratory findings in Uremic syndrome?

The most characteristic laboratory findings are increased concentrations of nitrogenous compounds in plasma such as urea and creatinine, as a result of reduced GFR and decreased tubular function.



How retention of urea and creatinine and of metabolic acids is followed?

Retention of urea and creatinine and of metabolic acids is followed by progressive hyperphosphatemia, hypocalcemia and potentially dangerous hyperkalemia

Kidneys fail to maintain adequate excretory, regulatory, and endocrine function.At least 90 organic compounds are retained in urea





What are another diseases of kidney?

These are diabetic nephropathy and hypertensive nephropathy.


How is diabetic nephropathy defined?

It is a clinical diagnosis based on the finding of proteinuria (albuminuria) in a patient with diabetes

It is the most common cause of end stage renal disease (ESRD)




What is hypertensive nephropathy


Hypertensive nephropathy considered another accelerating force in the development of ESRD.


What are Glomerular diseases?
What are Interstitial nephritis diseases?

  • Glomerular diseases

  • Immunoglobulin A nephropathy

  • Rapidly progressive glomerulonephritis

  • Acute nephritic syndrome

  • Nephrotic syndrome




  • Interstitial nephritis

  • Caused by a variety of chemical, bacterial, and immunological injuries to the kidney




What is the Polycistic kindney disease?
What causes Toxic nephropathy?
What is Obstructive uropathy?

  • Polycystic kidney disease

  • Is the most common inherited kidney disease presented by hypertension and gross hematuria.

  • Toxic nephropathy

  • Caused by a wide variety of nephrotoxins present in the environment like cadmium and lead.

  • Obstructive uropathy

Benign prostatic hypertrophy (BPH) is one of the most common type.

What are the different diseases of the kidney?

  • Tubular diseases

  • Renal tubular acidoses

  • Inherited tubulopathies

  • Diuretics

  • Diabetes insipidus

  • Renal calculi

  • Prostaglandins and NSAIDs in kidney disease

  • Monoclonal light chains and kidney disease




What is Dialysis of the kidney?

  • Dialysis

  • Is the process of separating macromolecules from ions and low molecular weight compounds in solution by the difference in their rates of diffusion through a semipermeable membrane.

Crystalloids (aqueous solutions of mineral salt) passed readily through this membrane, but larger substances (colloids) passed very slowly or not at all.



Explain dialysis procedures?

  • Dialysis procedures include:

  • Hemodialysis HD)

  • Is the most common method used to treat advanced and permanent kidney failure by connecting the patient to a hemodialyzer into which their blood flows.




  • Hemodiafiltration (HDF)

  • Is a method of treatment that combines hemodialysis and hemofiltration that yields more urea clearance than hemodialysis alone.



What is Peritoneal dialysis (PD)?

  • Peritoneal dialysis (PD)

  • Type of dialysis in which dialysate is introduced into the patient's peritoneal cavity and the peritoneum employed as the dialysis membrane




What is Kidney transplantation and how is it successful?

  • Kidney transplantation

  • Is the most effective form of renal replacement therapy (RRT) in terms of long-term survival and quality of life.




  • Successful transplantation requires:

  • 1. Preoperative assessment

  • 2. Postoperative assessment

  • 3. Therapeutic drug management




What are the criterias for kidney transplants?

  • Preoperative assessment

  • Criteria for acceptance include:

  • candidates should not be obese (body mass index (BMI) should be less than 40 kg/m²)



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