MLS CLINICAL CHEM BHCLR EXAM 4

Main functions of the kidneys

Remove waste and surplus substances from plasma; maintain water homeostasis; maintain electrolyte and acid-base status; endocrine regulation; gluconeogenesis

Nephron

Functional filtering unit of the kidney; about 1 million per kidney

6 parts of the nephron

Glomerulus; bowman's capsule; proximal convoluted tubule; loop of Henle; distal convoluted tubule; collecting duct

Glomerulus

Capillary tuft surrounded by Bowman's capsule; the main filter of the nephron

Loop of Henle

Connects the proximal and distal tubules

3 basic renal processes

Glomerular filtration; tubular reabsorption; tubular secretion

Glomerular filtration

First step; filters waste out of the blood

Tubular reabsorption

Needed substances move from the tubules back into the bloodstream

Tubular secretion

Waste and excess water are dumped into the distal tubule and sent to the bladder

Blood flow to the glomerulus

1200-1500 mL per minute

Nephron vs glomerulus filtering question

Choose glomerulus because it is more specific

Low GFR

Low blood filtration; indicates a kidney problem

What the glomerulus filters

Water; electrolytes; small dissolved solutes (based on size)

Substances too large to filter

Albumin and other plasma proteins

Normal glomerular filtrate

Mostly cell-free and protein-free

Proximal convoluted tubule reabsorbs

Some Mg and Ca; NaCl; 3/4 of water; all proteins; all vitamins; all amino acids; all glucose; some K+ and CO2

Where is ALL glucose reabsorbed

Proximal convoluted tubule

Renal threshold

Plasma concentration above which a substance spills into the urine

Ascending loop of Henle

Reabsorbs sodium and chloride; water is NOT reabsorbed

Descending loop of Henle

Reabsorbs or secretes water; does NOT reabsorb sodium or chloride

Distal convoluted tubule

Filtrate closest to final urine; makes small adjustments for electrolyte and acid-base homeostasis

Hormones controlling the DCT

ADH and aldosterone

ADH

Peptide hormone from the posterior pituitary; makes the DCT and collecting duct permeable to water; high in dehydration

Aldosterone

Made by the adrenal cortex; stimulates sodium reabsorption and potassium and hydrogen secretion in the DCT

Collecting duct

Final site for concentrating or diluting urine; controlled by ADH

Non-protein nitrogen (NPN)

Waste products from breakdown of nucleic acids; amino acids and proteins

3 primary NPN substances

Urea; creatinine; uric acid

Urea share of NPN

75% of daily NPN waste

Urea origin

Oxidative catabolism of proteins; amino acids are deaminated to ammonia which is converted to urea

Urea excretion route

Kidney is the only significant route

Urea molecular weight

60 Daltons; readily filtered by the glomerulus

Urea reabsorption

40-60% normally reabsorbed; depends on GFR; plasma renal flow and urine flow rate

Urea nitrogen is increased in

Prerenal and renal failure

Urea vs creatinine levels

Urea is about 10 times higher than creatinine

Creatinine

Waste product of muscle energy; level reflects muscle mass and is a constant daily value

Uric acid

Primary waste product of purine metabolism

Uric acid handling in kidney

Filtered then goes through a cycle of reabsorption and secretion; only 6-12% secreted

Uric acid at urine pH above 5.75

Ionized and more soluble (sodium urate)

Uric acid at urine pH below 5.75

Undissociated; increases stones (calculi) and gout

Uric acid is increased in

Leukemia; gout; renal disease

Sodium

Primary extracellular cation; excreted mainly by the kidneys; controlled only through excretion

Control of sodium balance

Renin-angiotensin-aldosterone system

Renin

Produced by the kidney

Ammonia handling in kidney

Not filtered; made in tubules from glutamine breakdown; combines with H+ to form NH4+ which is excreted in urine

Increased ammonia is seen in

Reye's syndrome; renal failure; chronic liver failure

Reye's syndrome cause

Aspirin given to young people can lead to organ failure

Primary endocrine functions of the kidney

Synthesis of renin; prostaglandins and erythropoietin

Erythropoietin

Made by the kidneys; stimulates RBC production

Best test of kidney function

Glomerular filtration rate (GFR)

When kidneys fail

Urea and creatinine build up; BUN rises more than creatinine

Creatinine clearance formula

(Ucr x Vur) / (Pcr x 1440) = CCl in mL/min

Ucr

Urine creatinine level (mg/dL)

Vur

Volume of urine in 24 hours (mL)

Pcr

Plasma creatinine level (mg/dL)

Minutes in 24 hours for clearance formula

1440

GFR

An estimation based on creatinine clearance

BUN to urea conversion

BUN x 2.14 = urea

Glomerular disease

Problem with the glomerulus causing increased waste in blood

Acute glomerulonephritis

Sudden inflammation of the nephron; often follows Group A beta-hemolytic strep infection

Acute glomerulonephritis findings

Hematuria (RBC casts); proteinuria; decreased GFR; anemia; increased BUN and creatinine; oliguria; sodium and water retention; possible heart failure

Chronic glomerulonephritis

Lengthy glomerular inflammation; can cause loss of functioning nephrons and uremia/azotemia

Nephrotic syndrome

Injured glomerular basement membrane with increased permeability; extreme proteinuria; hyperlipidemia; oval fat bodies in urine

Pyelonephritis

Infection of the kidney itself

Cystitis

Infection of the bladder

Oliguria

Decreased urine flow

Anuria

Practically no urine; less than 400 mL per day

BUN/creatinine ratio

10:1 to 20:1

BUN methods

Enzymatic with urease and L-glutamate dehydrogenase or direct measurement; early methods used the Berthelot reaction

Jaffe reaction

Creatinine reacts with picric acid in alkaline solution to form a red-orange color; more creatinine gives more color

Gout

Urate crystal deposits in connective tissue

Allopurinol

Treats increased nuclear catabolism (high uric acid)

Uric acid in renal disease

Increased but NOT the main indicator of renal failure

Uricase method

Catalyzes oxidation of urate; improves specificity

Ammonia source

Deamination of amino acids during protein catabolism; mainly from digestive and bacterial enzymes in the intestine

Ammonia measuring methods

Ion selective electrode; coupled enzymatic assay (most common on automation)

Ammonia specimen handling

Place on ice and refrigerate at 0-4 C within 20 minutes; avoid hemolysis

Why avoid hemolysis for ammonia

RBCs contain 2-3 times more ammonia than plasma

Ammonia in shed blood

Rises rapidly as proteins break down

Sodium function

Maintains osmotic pressure; reabsorbed in renal tubules under direction of ADH (vasopressin)

Hyponatremia

Decreased serum sodium

Addison's disease

Adrenal gland damage causing decreased aldosterone and cortisol

Aldosterone function

Balances potassium and sodium levels

Cortisol

Stress hormone

Potassium

Major cation of intracellular fluid; needed for muscle contraction and nerve function

Hypo and hyperkalemia effects

Heart arrhythmias and neuromuscular symptoms

Hypokalemia

Decreased serum potassium

Hypokalemia causes

Hyperaldosteronism; Cushing's syndrome; GI loss; intravascular hemolysis; diabetic ketoacidosis; severe burns

Potassium specimen handling

Spin immediately to prevent K shifting out of cells and falsely raising results

Causes of falsely elevated potassium

Hemolysis; EDTA contamination; fist clenching; prolonged tourniquet; clotted specimen

Sodium and potassium relationship

Na up means K down and vice versa

Chloride

Major anion of extracellular fluid; maintains hydration; osmotic pressure and anion-cation balance

Hypochloremia

Decreased serum chloride; seen in diabetic ketoacidosis; hypoaldosteronism and prolonged vomiting

Sweat chloride test

Used to diagnose cystic fibrosis

Carbon dioxide

Byproduct of normal metabolism; CO2; bicarbonate and carbonic acid together reflect total CO2 in serum

Anion gap

Difference between unmeasured cations and anions; also a quality control check for electrolyte assays

Anion gap formula with K

(Na + K) - (Cl + HCO3); reference 10-20 mmol/L

Anion gap formula without K

Na - (Cl + HCO3); reference 7-16 mmol/L

Abnormal anion gaps in multiple patients

Suggests a reagent or analyzer problem; investigate

Increased anion gap

High alcohol and salicylates; ketones

Decreased anion gap

High serum Mg; high serum Ca; lithium therapy