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Manifestation of Novel Social Challenges of the European Union in the Teaching Material of Medical Biotechnology Master’s Programmes at the University of Pécs and at the University of Debrecen

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(1)

Medical Biotechnology Master’s Programmes

at the University of Pécs and at the University of Debrecen

Identification number: TÁMOP-4.1.2-08/1/A-2009-0011

(2)

CHANGES OF RENAL FUNCTIONS

IN THE ELDERLY

Miklós Székely and Erika Pétervári

Molecular and Clinical Basics of Gerontology – Lecture 11

Medical Biotechnology Master’s Programmes

at the University of Pécs and at the University of Debrecen

Identification number: TÁMOP-4.1.2-08/1/A-2009-0011

(3)

With aging:

• Renal mass decreases

• Renal blood flow (RBF) decreases

• Number of functioning nephrons decreases

• GFR decreases, glomerular dysfunctions

• Tubular dysfunctions

• Excretory capacity decreases

• Role in salt/water regulation decreases

• Role in pH regulation decreases

• Non-excretory renal functions decrease

AGING vs. RENAL FUNCTIONS

(4)

Macula densa

Red blood cells Podocyte

(visceral layer)

Mesangial cell

Basement membrane

Parietal layer of Bowman’s capsule

Afferent arteriole Efferent arteriole

Distal renal tubule

Glomerular structures

(5)

Glomerular structures

Red blood cell

Podocytes (visceral layer)

Mesangial cell

Basement membrane Capillary

(6)

Glomerular structures:

filter surface

Podocyte (epithelial cell with foot processes)

Mesangial cell

Red blood cell

Endothelial cell

Capillary lumen

Foot processes

Basement membrane

Red blood cell Capillary lumen

Bowman’s space

Fenestrations

(7)

filtration of polyanions  accumulation of circulating aggregates in mesangium fusion of podocyte

foot processes

proteinuria mesangial matrix

production and proliferation focal sclerosis

Anionic charge of glomerular capillaries 

Development of

glomerulosclerosis 1

(8)

Glomerular sclerosis

Glomerular sclerosis

(9)

Chronic loss of renal tissue

Protein intake Diabetes mellitus

hyperglycemia Hypertrophy and vasodila-tion

in remaining nephrons Glomerular

pressure 

Altered permselectivity Arterial pressure

Glomerular hyperfiltration

Direct cellular injury

Cell proliferation and platelet aggregation

Mesangial matrix overproduction

Glomerular sclerosis Increased protein

filtration

Compensatory polyuria

Albuminuria Mesangial cell damage

Development of

glomerulosclerosis 2

(10)

Percent of total nephrons

SNGFR (nl/min)

0 10 20 30

0 0 10 20 30 40 50 60 70 80 (37.5

) GFR

100%

0 10 20 30

0 0 10 20 30 40 50 60 70 80 (20)

GFR

~50%

0 10 20 30

0 0 10 20 30 40 50 60 70 80 (37.5

40 )

GFR 100%

Aging influences single-nephron-GFR

(SNGFR)

(11)

GFR (ml/min)

Years

40

20 60

80 10

0 12

0 14

0

30 40 50 60 70 80

Age vs. GFR

(12)

• In th elderly GFR, tendency for azotemia due to a fall of kidney perfusion (thirst, heat, CO redistribution e.g. heart failure), but no proportional rise in se-

creatinine (less muscle lost)

• Tubular reabsorption changes: glucose reabsorbing tubular cells still function, minerals: tendency for K- loss, salt wasting (Na-reabsorption), phosphaturia,

poor ADH action (water loss).

• Proteinuria more frequent.

• Excretory capacity (drugs!) decreases.

• Severe shifts in the osmotic pressure.

Age vs. nephron dysfunctions

(13)

ADH effect decreases with age

U/P inulin (urine/plasma conc. ratio)

Urine Collection Period

0 0 10 20 30 40 50 60 70 80 90 100 110 120

1 2 3 4 5 6 7 8 9 10

Young Middle Old

ADH

(14)

80

300

400

600

1,000 1,500 Osmotic pressure Proximal tubule

Distal tubule

Corticomedullary osmotic

concentration gradient

(15)

No ADH

16 ml

1500

1200

900

600

300

0

Osmolality (mOsm/kg)

100 ml

20 ml

20 ml

2.0 ml

0.3 ml

Lot of ADH

Prox. tub. Loop of Henle Dist. tub + Cort.

collecting duct

Medullary collecting

duct

Concentrating and diluting the urine

Normal

Hyposthenuria

20 ml

Fluid volume along the nephron

(16)

Specific gravity of urine

Number of nephrons

1,000

2,000,000 1,500,000 1,000,000 500,000 0

1,010 1,020 1,030 1,040

Hyposthenuria

Development of hyposthenuria

Isosthenuria

Specific gravity of plasma

(17)

• Impaired excretion of substances that are excreted through the kidneys  the dose of drugs that are

eliminated through the kidney has to be decreased!

• Kidney perfusion decreases frequently for a number of reasons, e.g. redistribution in heart failures,

exsiccosis – impaired excretory functions – drug doses have to be adjusted.

Kidney and drugs

(18)

• Atrophy of renal parenchyma + sclerotic a. renalis

 regulation of blood pressure defective, tendency for hypertension, but hypovolemia may cause

hypotension.

• Erythropoietin deficiency due to reduced renal parenchyma and gonadal hormon secretion

anemia.

• Active D-vitamin formation decreases  bone abnormalities (senile osteoporosis).

Aging vs. non-excretory kidney

functions

(19)

Most common renal diseases and

genitourinary conditions in the elderly

• Diabetic nephropathy

• Glomerulonephritis

• Pyelonephritis

• Interstitial nephropathy

- analgesic nephropathy - uric acid nephropathy - myeloma kidney

• Urinary retention

(The muscles of the bladder and pelvic floor weaken.)

• Urinary incontinence

(The capacity of the urinary bladder reduces which leads to frequent urination.)

• Urinary infections

• Benign prostatic

hyperplasia, prostate cancer

• Atrophic vaginitis

(20)

Renal failure in the elderly:

causes

The incidence of acute renal failure increases following acute tubular necrosis.

Risk factors:

• age-related decrease of RBF, GFR, and of ability to concentrate or to dilute urine,

• diabetes mellitus,

• hepatic cirrhosis,

• congestive heart failure,

• drugs

Chronic ischemic renal disease and

progressive damage of the renal parenchyma lead to chronic renal failure.

Risk factors:

• diabetes mellitus

• hypertension

• hyperlipidemia

• obesity

(21)

Renal failure in the elderly:

dialysis and kidney transplantation

The most common indication of dialysis due to chronic renal failure is diabetic nephropathy (35-40%). There is an increase in the

number of renovascular diseases.

Among the dialyzed there are less candidates for transplantation due to co-morbidity.

The overall survival increases due to the improved efficacy of dialysis.

With higher capacity of dialysis, the age-related limits of dialysis have faded away.

Age is not a contraindication of kidney transplantation. Both the cadaveric and the living donor can be an option in the elderly.

The only limiting factor for kidney transplantation is the presence of multimorbidity (hypertension, DM, significant atherosclerosis).

(22)

Urinary tract infection

Symptoms: fever, dysuria (pain upon urination),

urgency, frequency, incontinence, impaired physical and/or mental status. Sepsis can develop quickly and atypically — treatment of urosepsis is extremely

difficult.

Pathogens: E. Coli, Enterococci, Streptococci, Proteus.

Treatment: oral rehydration, frequent urination, selected antibiotics, roboration.

(23)

Incontinence

Definition:

Involuntary loss of urine through the urethra.

Types:

• functional,

• stress,

• urge, reflex,

• overflow.

(24)

Functional incontinence

The patient is not able to control his bladder due to altered circumstances.

Causes:

• disability,

• impaired vision,

• dementia,

• bigger amount of urine (i.e. diuretics, diabetes mellitus)

Management:

• changes in the environment,

• timed voiding (scheduled bathroom visits),

• urinary indwelling catheter as required,

• diapers.

(25)

Stress incontinence

Involuntary loss of urine upon elevated intra- abdominal pressure.

Causes:

• urethral sphincter insufficiency due to weakness of pelvic floor musculature,

• obesity,

• prolapsed uterus, atrophic vaginitis, bladder hernia.

Management:

• weight loss,

• Kegel exercises, electro-stimulation,

• estrogen, medication (Ditropan, Melipramin),

• surgery,

• panty liners.

(26)

Urge/reflex incontinence

Sudden, unexpected urge to void after certain stimuli.

Causes:

• atrophic vaginitis, cystitis,

• benign prostatic hyperplasia (BPH),

• certain drugs or foods, cold.

Management:

• casual treatment,

• avoiding coffee/tea/alcohol,

• estrogen, medication (Ditropan),

• electro-stimulation, behavioral training (biofeedback).

(27)

Overflow incontinence

Unexpected urine loss from the overfilled bladder.

Causes:

• benign prostatic hyperplasia (BPH),

• fibrotic stenosis of the urethra,

• muscles of the bladder and pelvic floor weak.

Management:

• casual treatment,

• avoiding coffee/tea/alcohol,

• estrogen, medication (Ditropan),

• behavioral training (biofeedback).

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