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Renal Structure and Function

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Kidneys

• Paired• Retroperitoneal• Partially protected by the 11th and 12th ribs• Right slightly lower due to liver• Surrounded by renal capsule• Adipose capsule• Renal fascia

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Anatomy

• Hilum (hilus)• Renal artery and vein• Cortex • Medulla• Renal pyramids and renal papillae• Major and minor calyces• Renal Pelvis• Ureters

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• Ureters connect kidneys to urinary bladder

• Urethra leads from bladder outside the body

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• Kidneys make up 1 % of body mass, but receive about 25% of cardiac output.

• Kidney has two major functions:1. Filtration of blood

• Removes metabolic wastes from the body, esp. those containing nitrogen

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2. Regulation:Blood volume and compositionElectrolytesBlood pHBlood pressure

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Nephron

• Functional unit of the kidney• Filtration, tubular reabsorption, tubular

secretion• Renal corpuscle:

– Glomerulus – capillaries– Glomerular or Bowman’s capsule

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• Bowman’s capsule– Receives filtrate

• Proximal convoluted tubule– Reabsorption of water and solutes

• Nephron loop or Loop of Henle– Regulates concentration of urine

• Distal convoluted tubule and Collecting duct

• Reabsorption of water and electrolytes–ADH, aldosterone, ANP

– Tubular secretion

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NEPHRON: Overview

1: Interlobular artery2: Interlobular Vein3: Glomerulus/Bowman’s

Capsule4. Distal Tubule5. Proximal Tubule6: Loop of Henle7: Collecting Duct

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Filtration

• Renal corpuscle• Filtration membrane

– Fenestrated endothelium of capillaries– Basement membrane of glomerulus– Slit membrane between pedicels of podocytes

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Forces that influence filtration

• Glomerular blood hydrostatic pressure

• Opposing forces:– Plasma colloid osmotic pressure– Capsular hydrostatic pressure

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Glomerular Filtration Rate

• Volume of plasma filtered / unit time• Approx. 180 L /day• Urine output is about 1- 2 L /day• About 99% of filtrate is reabsorbed

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Glomerular Filtration

• Rate (GFR): 120 mL/min (normal)• Substances “Filtered”:

– water, electrolytes (Na, K, etc.), sugars (glucose), nitrogenous waste (urea, creatinine)

• Substances “Excluded”:– Substances of size > 70 kDa– Plasma protein bound substances

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GFR influenced by:

• Blood pressure and blood flow• Obstruction to urine outflow• Loss of protein-free fluid • Hormonal regulation

– Renin – angiotensin – Aldosterone– ADH– ANP

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Juxtaglomerular apparatus

• Juxtaglomerular cells lie in the wall of afferent arteriole

• Macula densa in final portion of loop of Henle – monitor Na+ and Cl- conc. and water

• Control blood flow into the glomerulus• Control glomerular filtration

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Tubular reabsorption

• Water, glucose, amino acids, urea, ions• Sodium diffuses into cell; actively pumped

out – drawing water with it

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Tubular Resorption • Proximal Tubules: GF: 120-125 mL/min

– Reabsorption of Na (55%), Cl, phosphate, amino acids, glucose and bicarbonate (85%). Secretion of proton (CA)

• Loop of Henle: (30 mL/min)– Na/K/2Cl Cotransporter (25% Na reabsorbed)– Water impermeable: Hypertonic medullary inst– Ca & Mg paracellular diffusion

• Distal Tubules:– EDT: Na/Cl cotransporter; Ca/Na counter transport– LDT: Na Channels, K channels, H pump: Aldosterone reg.

• Collecting Tubules: 5-10 mL/min– Water channels: Vasopressin regulated

• Ureters: 1-2 mL/min (stored inbladder until voiding)

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• In addition to reabsorption, also have tubular secretion – substances move from peritubular capillaries into tubules – a second chance to remove substances from blood.

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• By end of proximal tubule have reabsorbed:

• 60- 70% of water and sodium• about 100% of glucose and amino acids• 90 % of K+, bicarb, Ca++, uric acid• Transport maximum – maximum amount

of a substance that can be absorbed per unit time

• Renal threshold – plasma conc. of a substance at which it exceeds Tm.

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Loop of Henle

• Responsible for producing a concentrated urine by forming a concentration gradient within the medulla of kidney.

• When ADH is present, water is reabsorbed and urine is concentrated.

• Counter-current multiplier

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Distal convoluted tubule and collecting ducts

• What happens here depends on ADH• Aldosterone affects Na+ and K+• ADH – facultative water reabsorption• Parathyroid hormone – increases Ca++

reabsorption

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Distal convoluted tubule and collecting ducts

• Tubular secretion to rid body of substances: K+, H+, urea, ammonia, creatinine and certain drugs

• Secretion of H+ helps maintain blood pH(can also reabsorb bicarb and generate new bicarb)

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Summary of Tubular Resorptive Processes

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The Role of ADH• The water potential of the tissue fluid in the medulla is

always more negative than that of the filtrate in the collecting duct.

• Whether the water actually leaves the collecting duct (by osmosis) is determined by the hormone ADH (anti-diuretic hormone)

• Osmoreceptors in the hypothalamus detect the low levels of water,so the hypothalamus sends an impulse to the pituitary gland which releases ADH into the bloodstream.

• ADH makes the wall of the collecting duct more permeable to water.

• Therefore, when ADH is present more water is reabsorbed and less is excreted.

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Regulation of Renal Function

• Tubuloglomerular feedback• Medullary Vasoconstriction• Medullary Vasodilation• Inhibition of transport in the thick

ascending limbs

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Regulation of Renal Function • Tubuloglomerular Feedback:

Regulation of GFR in response to solute concentration in the distal tubule:– macula densa (PCT): Afferent arteriolar

vasoconstriction in response to high tubular Na (Decr GFR)

– Juxtaglomerular apparatus (Afferent): Renin release and angiotensin II formation with low perfusion pressure (Aldosterone secretion and Na and water retention)

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Regulation of Renal Function

• Cortical Flow: Adequate to maintain GFR• Medullary Blood Flow and Oxygen demand:

– Important for nephron cell survival and function (oxygen is required for ATP, used in trnasporters)

• Too high: Disruption of osmolar gradient of counter-current exchange mechanism

• Too low: hypoxic injury– Modulators

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Regulation of Renal Function• Adaptive Changes:

– Glomerular hyperfiltration (increased GFR per nephron) nephron loss. ( may progress to chronic renal failure).

– Neural and Hormonal regulation: low perfusion results in afferent arteriolar vasodilation and efferent arteriolar vasconstriction

– Alteration in Na systemic balance– Renal nerve (sympathetic)

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The Kidney and Physiologic Regulation: Blood Pressure

• Macula Densa and Na concentration• Juxtaglomerular Apparatus and Renin release

and angiotensin II production– Direct vasoconstriction– Aldosterone Secretion: na and water rentention

• Vasopressin and intravascular volume depletion: Enhanced water resorption at the collecting ducts

• Morphologic: i.e. number of nephrons, etc.

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The Kidney and Physiologic Regulation: Calcium Metabolism

• Formation of the active form of vitamin D required for Ca absorption from gut, etc.

• Site of Parathyroid Hormone action: Ca retention and phosphate wasting (see earlier endocrine lectures)

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The Kidney and Physiologic Regulation: Erythropoiesis

• Erythropoietin stimulates bone marrow production and maturation of RBCs.

• Profound anemia in ESRD:– hematocrits 20-25%– Therapy: Erythropoietin administration

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Renal diagnostic procedures

• Urinalysis is non-invasive and inexpensive• Normal properties are well known and

easily measured

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pH

• Normally 4.8 – 8.0• Higher in alkalosis, lower in acidosis• Diabetes and starvation ↓ pH • Urinary infections ↑ pH

– Proteus and pseudomonas are urea splitters

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Specific gravity

• Normal values 1.025 -1.032• High specific gravity can cause

precipitation of solutes and formation of kidney stones

• When tubules are damaged, urine specific gravity approaches that of glomerular filtrate – 1.010 – remains fixed = 2/3 of nephron mass has been lost

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• Diabetes insipidus = 1.003• Diabetes mellitus = 1. 030• Emesis or fever = 1.040

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Microscopic analysis

• Red blood cells – should be few or none– Hematuria – large numbers of rbc’s in urine– Catheterization– Menstruation– Inflamed prostate gland– Cystitis or bladder stones

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• Casts – precipitate from cells lining the renal tubules– Red cells – tubule bleeding– White cells – tubule inflammation– Epithelial cells – degeneration, necrosis of

tubule cells

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• Crystals –– Infection– Inflammation– stones

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• White blood cells – Pyuria– Urinary tract infection

• Bacteria

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Substances not normally present in urine

• Acetone• Bile, bilirubin• Glucose• Protein – albumin

– Renal disease involving glomerulus

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Blood Urea Nitrogen BUN

• Urea produced by breakdown of amino acids - influenced by diet, dehydration, and hemolysis

• Normal range 10-20 mg/ dL• If the GFR decreases due to renal disease

or blockage, or decreased blood flow to kidney - BUN increases

• General screen for abnormal renal function

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Creatinine clearance

• Creatinine is an end product of muscle metabolism

• Muscle mass is constant; creatinine is constant

• Normal 0.7 – 1.5 mg/ dL in plasma• Can then be compared to creatinine in

urine over 24 hour period to determine clearance

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• Creatinine clearance is an indirect measure of GFR and renal blood flow

• Creatinine is neither reabsorbed nor secreted, just freely filtered.

• Amount excreted = amount filtered• Useful to monitor changes in chronic renal

function• Increases with trauma with massive

muscle breakdown

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Diagnostic testing

• Inulin clearance - not absorbed or secreted = GFR

• PAH – para-aminohippuric acid – not absorbed ; actively secreted = renal plasma flow

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Chronic renal failureand common accompanying diseases

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Etiology

• can be found in every age highly depending on educational, social and hence nutritional status

• is either acquired or inherited• occurs with higher probabilities in certain

diseases (e.g. diabetes mellitus, arteriosclerosis, arterial hypertonia, viral diseases)

• occurs with higher probabilities in older people

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Definition

• we speak of a chronic kidney disease, if there is either:

1. proteinuria or microalbuminuria2. or a kidney function of less than 60% of

normal3. or a pathological alteration of the kidneys4. and if this situation if present for more

than 3 months

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Measurement of kidney function

• achieved by measurement of creatinin (metabolic waste product) concentration in the blood (physiological: 50 – 120 µmol/L)

• estimation of glomerular filtration rate (GFR) by usage of a formula

creatinin clearance (= rate of expulsion from the body)

creatinin clearance =concentration of creatinin in the urine * volume of

urineconcentration of creatinin in the plasma * time

creatinin

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5 stadia after KDOQI

= renal disease outcomes quality initiative• based on the ultra-filtration rate of the glomeruli

in the kidney

Stadium GFR with proteinuria without proteinuria

1 > 89 renal disease with normal function normal finding

2 60 – 89 renal disease with mild renal insufficiency

mild renal insufficiency, but no renal disease

3 30 – 59 renal disease with moderate renal insufficiency

4 15 – 29 renal disease with heavy renal insufficiency

5 < 15 chronic renal failure

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http://www.unckidneycenter.org/kcpp/index.htm

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Role of the kidney

removal of metabolic waste products• water balance• electrolyte balance• acid-base balance• removal of medications and toxic substances• release of hormones:

– renin (blood pressure)– erythropoietin (eryhtropoiesis)– Vitamin D3 (metabolism of the bones)

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diseases occurring with renal insufficiency

diseases leading to renal

insufficiency

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Percentual distribution of diagnoses at the beginning of renal substitution therapy

Year 1996 1997 1999 2000 2001 2002 2003 2004 2005

diabetes mellitus II 24 29 30 31 32 32 33 31 32

nephrosklerosis 14 16 16 15 17 18 20 22 23

glomerulonephritis 16 15 14 15 14 14 14 12 13

interstitial nephritis 13 11 11 10 9 9 8 8 8

unknown genesis 11 9 10 9 10 9 9 9 8

cystic kidneys 6 6 6 6 6 5 5 5 4

systemic diseases 4 4 4 4 3 4 4 4 4

various 4 4 3 4 4 4 4 4 4

diabetes mellitus I 7 6 6 5 4 4 3 3 3

congenital diseases 1 1 1 1 1 1 1 1 1

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1996

24%

14%

16%13%

11%

6%

4%

4%7% 1%

2005

32%

23%

13%

8%

8%

4%

4%4%

3% 1%

diabetes mellitus II nephrosclerosis glomerulonephritis interstitial nephritisunknown genesis cystic kidneys systemic disease variousdiabetes mellitus I congenital disease

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terminal renal insufficiency & treatment possibilities

1. hemodialysis2. peritoneal dialysis3. transplantation

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1. hemodialysis

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2. peritoneal dialysis

cannot be applied indefinitely due to sclerosis of the endothelium

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3. transplantation

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prevention of renal insufficiency

• healthy nutrition in combination with exercise

• balanced blood pressure• balanced diabetes (treatment with insulin)• sufficient water intake (approx. 2L of water

a day) in all cases prevention is the better way

to go for rather than acute treatment

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economical aspects of renal insufficiency

• 60.000 people in Germany need to go to dialysis (94% hemodialysis, 6% peritoneal dialysis)

• treatment of a patient costs cca 50.000 – 60.000€ per year

• a transplantation surgery costs cca. 30.000€ and the costs for sustaining the transplant within the patient cca. 20.000 – 25.000€ a year

costs of transplant would already be amortized after one year

• waiting list: 12.000 – 15.000 patients 3.000 patients are receiving a draft organ

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sneak peek into the future

• health prevention subject at school• optimization of dialysis treatment

– reusage of dialysators– more adequate solutions for peritoneal dialysis

• optimization of transplantation– living donation– optimization of legitimate principles– xenotransplantation– artificial organs produced by monoclonal stem cells

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Sources

• http://de.wikipedia.org• http://www.fresenius.de• http://www.unckidneycenter.org/kcpp/inde

x.htm• http

://www.nephrologe.de/patient/erkrankungen/nierenversagen/chr_nierenvers1.htm