The Renal Function. Anatomy The kidneys are a pair of fist-sized organs that are located on either side of the spinal column. A kidney consists of

The Renal Function

Anatomy

The kidneys are a pair of fist-sized organs that are located on either side of the spinal column.

A kidney consists of an outer layer (renal cortex) and an inner region (renal medulla).

The functional unit of the kidney is the nephron.

M. Zaharna Clin. Chem. 2009

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Nephron

Structural and functional unit of the kidney

1 million nephrons per kidney Consists of 2 parts

1. Glomerulus (filtering system) tuft of capillaries surrounded by

Bowman’s capsule

2. Tubules


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Nephron


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Renal artery

Glomerulus

Bowman’s capsule

Proximal tubule

Distal tubule

Collecting duct

Henle’s Loop

Afferent arteriole

Nephron - Bowman’s capsule

Bowman’s capsule: funnel with tubules as stem

Blood carried to glomerulus by afferent arteriole

Afferent arteriole divides to form capillary network.

These capillaries reunite to form efferent arteriole, which carries blood out of the glomerulus


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Nephron - Bowman’s capsule

Blood filtered in glomerulus; some water and small molecules removed Size cutoff value of approximately 66,000 Da,

about the molecular size of albumin. Glomerular filtrate collected in

Bowman’s capsule and enters tubules. Specific reabsorption occurs in tubules.

Most water and soluble nutrients reabsorbed


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Tubule System Proximal convoluted tubule

located in the cortex Reabsorption of Glucose,

water, amino acids, Na, Cl & others Loop of Henle

composed of the thin descending limb, which spans the medulla, and the ascending limb, which is located in both the medulla and the cortex,

More water reabsorbed Distal convoluted tubule

located in the cortex Sodium and hydrogen ion reabsorption


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Tubule System The collecting duct

formed by two or more distal convoluted tubules as they pass back down through the cortex and the medulla to collect the urine that drains from each nephron.

collecting tubules, then ureters → bladder → urethra


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1000 liter of blood through glomerulus per day; 100 liters of glomerular filtrate formed; 1 liter of urine produced

Functions of Kidney

Urine formation Regulate body fluid, osmolality and

volume Regulate electrolyte balance Regulate acid-base balance Excrete waste products and foreign

substances Produce and excrete hormones


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Urine Formation Removal of potentially toxic waste

products 3 processes involved

Filtration, Reabsorption, Secretion


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• Substance A is filtered and secreted, but not reabsorbed; • Substance B is filtered and a portion reabsorbed• Substance C is filtered and completely reabsorbed

Glomerular Filtration Glomerular filtration rate (GFR) is

approximately 130 mL/min Cells and large plasma proteins

unable to pass through the semipermeable membrane

Glomerular filtrate is essentially plasma without proteins.

water, electrolytes, glucose, amino acids, low-molecular-weight proteins, urea, and creatinine, pass freely through the basement membrane and enter the proximal convoluted tubule


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Proximal Convoluted Tubules

The next part of the nephron to receive filtrate

This filtrate contains waste products, and substances that are valuable to the body.

One function of the PCT is to return the bulk of each valuable substance back to the blood circulation. Glucose, water, amino acids, Na, Cl & others

Organic acids and bases, hydrogen ions and ammonia may be secreted into the tubular fluid


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Proximal Convoluted Tubules

Reabsorption may be active or passive Active — against a concentration

gradient (glucose, amino acids, low mw proteins, sodium, etc.) — regulated by kidney according to levels of

these substances in the blood Passive — no energy involved — water

and urea Tubular secretion may also be

passive or active M. Zaharna Clin. Chem. 2009

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Loop of Henle Descending limb is highly permeable

to water Passive reabsorption of water in

descending loop Ascending loop is impermeable to

water but actively reabsorbs sodium and chloride

it lowers the salt concentration


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Distal Convoluted tubule

The function is to effect small adjustments to achieve electrolyte and acid-base homeostasis

Small amount of sodium, chloride, water are reabsorbed

Under influence of AVP (ADH) increase water permeability of tubule (reabsorbs water)

Potassium also reabsorbed or secreted Aldosterone - sodium reabsorption and

potassium secretion


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Collecting Duct The collecting ducts are the final

site for either: concentrating or diluting urine

Also under control of ADH & aldosterone Reabsorption of water, sodium and

chloride


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Regulation of Fluid and Electrolyte Balance Water:

body water (weight) remains constant day to day — ability of kidney to excrete or conserve water

Water balance is controlled by voluntary intake (thirst) and urinary loss

Sodium: freely filtered through the glomerulus and

reabsorbed by tubules Active reabsorption of Na+ results in passive

transport of Cl- and bicarbonate and passive reabsorption of water.


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Potassium: Both the distal convoluted tubule and the

collecting ducts can reabsorb and excrete potassium, and this excretion is controlled by aldosterone

Chloride: parallels sodium but reabsorption is passive in proximal tubules and active in distal tubules and collecting duct


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Regulation of Fluid and Electrolyte Balance


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Acid-Base Balance

Secretion of hydrogen ions from tubular cells Hydrogen ions generated in proximal and

distal tubules as a result of carbonic acid

H2O+CO2 → H2CO3 → H + HCO3-

React with bicarbonate ions React with buffers — phosphate ions React with ammonia (deamination of

gluatamine) to form ammonium ion Excretion as free hydrogen ions


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Nitrogenous Waste Excretion

When low GFR, levels of nitrogenous wastes increase in blood — NPN’s Urea Creatinine Uric Acid


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Primary Endocrine Functions

Kidneys synthesize renin, prostaglandins and erythropoietin

Renin: Renin is the initial member of the

renin-angiotensin-aldosterone system help regulate sodium and potassium in

the blood, fluid levels in the body, and blood pressure.


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Prostaglandins A group of potent cyclic fatty acids Behave like hormones Prostaglandins produced by the kidney

increase renal blood flow, sodium & water excretion

They oppose renal vasoconstriction due to angiotensin


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Erythropoietin It is a single chain polypeptide. It is produced by cells close to the proximal

tubules. Its production is regulated by blood oxygen

levels "hypoxia increases its production". Erythropoietin acts on the erythroid progenitor

cells in the bone marrow, causing their maturation and increasing the number of RBCs.

In chronic renal insufficiency, erythropoietin production is significantly reduced causing anemia.


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Secondary Endocrine Functions

The kidneys are the target locus for the action of aldosterone

For the catabolism of insulin, glucagon and aldosterone

The point of activation for vitamin D


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Renal Disorders

Acute Glomerulonephritis Nephrotic Syndrome Tubular Diseases Urinary Tract Infection Acute Renal Failure


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Acute Glomerulonephritis

Acute inflammation of the glomeruli Results in oliguria, hematuria,

increased BUN and serum creatinine, decreased GFR and hypertension

Red cell cast finding are of great importance

Proteinuria also present


27Red cell cast

Nephrotic Syndrome Massive proteinuria, edema,

hypoalbuminemia, hyperlipidemia, and lipiduria

Has many cuases Characterized by increased

glomerular membrane permeability — loss of protein (greater than 2-3 grams per day)


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Tubular Diseases Depressed secretion or reabsorption

of specific biochemicals Or Impairment of urine dilution and

concentration mechanisms Renal Tubular Acidosis — most

important Low values of phosphorus in serum,

and presence of glucose and amino acids in urine


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Urinary Tract Infection Bladder — cystitis Kidneys — pyelonephritis Bacterial concentrations

>100,000 colonies/mL is considered diagnostic for infection

Increased number of white blood cells

Increased number of red blood cells may be present

White blood cell casts is considered diagnostic of pyelonephritis


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Acute Renal Failure Defined as occurring when the GFR is

reduced to less than 10 mL/minute. Prerenal — before blood reaches the

kidney Hypovolemia Cardiovascular failure

Renal — occuring in kidney Acute tubular necrosis Glomerulonephritis

Postrenal — after urine leaves kidney Obstruction


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Usually accompanied by oliguria Associated with varying degrees of

proteinuria, hematuria, and presence of red cell casts and other casts

BUN and creatinine increase rapidly Can progress to chronic renal

insufficiency or failure


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Renal Calculi Renal calculi, or

kidney stones, are formed by the combination of various crystallized substances. Of these, calcium oxalate stones are by far the most commonly encountered


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Renal Function Tests Tests of Glomerular Function

Creatinine Clearance Most sensitive method of assessing renal

function Tests of Tubular Function

Concentration — Dilution Studies Non-protein nitrogen compounds

Urea nitrogen Creatinine Uric acid

Urinalysis and Microscopy pH, Chemical Analyses (glucose, protein,

bilirubin/urobilinogen & others)M. Zaharna Clin. Chem. 2009

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Renal Function Tests Cystatin C is a low-molecular-weight protein

produced by nucleated cells. It is freely filtered by the glomerulus, reabsorbed, and

catabolized by the proximal tubule. Produced at a constant rate, levels remain stable if

kidney function is normal. Plasma concentrations appear to be unaffected by

gender, race, age, and muscle mass. Studies have shown measurement of cystatin C to be

at least as useful as serum creatinine and creatinine clearance in detecting early changes in kidney function.

A rise in cystatin C is often detectible before there is a measureable decrease in GFR or increase in creatinine.

Cystatin C can be measured by immunoassay methods. M. Zaharna Clin. Chem. 2009

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Renal Function Tests

β2-Microglobulin is a small, peptide found on the surface of

most nucleated cells levels of β2-M remain stable in normal

patients β2-M is easily filtered by the glomerulus.

About 99.9% is then reabsorbed by the proximal tubules and catabolized.

Measurement of serum β2-M is used clinically to assess renal tubular function in renal transplant patients, with elevated levels indicatingorgan rejection


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Microalbumin The term microalbuminuria describes small

amounts of albumin in urine Urine microalbumin measurement is important in

the management of patients with diabetes mellitus, who are at serious risk of developing nephropathy over their lifetimes

Increased glomerular capillary permeability. This permeability allows small (micro) amounts of albumin to pass into the urine.

If detected in this early phase, rigid glucose control, along with treatment to prevent hypertension, can be instituted and progression to end-stage renal disease (ESRD) prevented.


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Case Study

Jennie had a sore throat. She did not go to the doctor and recovered without medication.

However, a few weeks later Jennie was still listless and unwell.

She noticed that her urine was very dark and tinged red; she was also not producing much urine.

Jennie’s mother took her to their primary care physician.


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Test Result

Antistreptolysin-O (ASO) titer

Positive

Plasma creatinine Increased

Blood urea nitrogen Increased

Plasma sodium Increased

Creatinine clearance. Increased

Protein in urine Positive

Red blood cell casts Positive


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Comment As a consequence of Jennie’s streptococcal

infection, a portion of the functional units in Jennie’s kidney lost their ability to filter waste products from her blood.

The infection provoked an antibody response, which resulted in the formation of antigen-antibody complexes circulating in her blood, as indicated by her high ASO titer.

The complexes caused inflammation of the renal glomeruli, which resulted in reduction of the filtration capability of the glomeruli and, consequently, the reduction of the flow of waste products from blood to urine.


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Documents

The Renal Function. Anatomy The kidneys are a pair of fist-sized organs that are located on either side of the spinal column. A kidney consists of