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 Identification number: TÁMOP /1/A

CHANGES OF RENAL FUNCTIONS IN THE ELDERLY Miklós Székely and Erika Pétervári Molecular and Clinical Basics of Gerontology – Lecture 11 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 Identification number: TÁMOP /1/A

TÁMOP /1/A 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

TÁMOP /1/A 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

TÁMOP /1/A Glomerular structures Red blood cell Podocytes (visceral layer) Mesangial cell Basement membrane Capillary

TÁMOP /1/A Glomerular structures: filter surface Podocyte (epithelial cell with foot processes) Mesangialcell Red blood cell Endothelialcell Capillary lumen Foot processes Basement membrane Red blood cell Capillary lumen Bowman’s space Fenestrations

TÁMOP /1/A 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  1 Development of glomerulosclerosis 1

TÁMOP /1/A Glomerular sclerosis

TÁMOP /1/A Chronic loss of renal tissue Protein intake Diabetes mellitus hyperglycemia Hypertrophy and vasodila-tion in remaining nephrons  Glomerular pressure  Altered permselectivity Altered permselectivity  Arterial pressure  Glomerular hyperfiltrati on Direct cellular injury Cell proliferation and platelet aggregation Mesangial matrix overproduction Glomerular sclerosis Increased protein filtration Compensatory polyuria Albuminuria Mesangial cell damage 2 Development of glomerulosclerosis 2

TÁMOP /1/A Percent of total nephrons SNGFR (nl/min) (37. 5) GFR100% (20 ) GFR~50% (37. 5) 40 GFR100% Aging influences single- nephron-GFR (SNGFR)

TÁMOP /1/A GFR (ml/min) Years Age vs. GFR

TÁMOP /1/A 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

TÁMOP /1/A ADH effect decreases with age U/P inulin (urine/plasma conc. ratio) Urine Collection Period Young Middle Old ADH

TÁMOP /1/A ,000 1,500 Osmotic pressure Proximal tubule Distal tubule Corticomedullary osmotic concentration gradient

TÁMOP /1/A No ADH 16 ml Osmolality (mOsm/kg) 100 ml 20 ml 2.0 ml 0.3 ml Lot of ADH Prox. tub.Loop of HenleDist. tub + Cort. collecting duct Medullar y collecti ng duct Concentrating and diluting the urineNormal Hyposthenuria 20 ml Fluid volume along the nephron

TÁMOP /1/A Specific gravity of urine Number of nephrons 1,000 2,000,0001,500,0001,000,000500,0000 1,010 1,020 1,030 1,040 Hyposthenuri a Development of hyposthenuria Isosthenur ia Specific gravity of plasma

TÁMOP /1/A Impaired excretion of substances that are excreted through the kidneys  the dose of drugs that are eliminated through the kidney has to be decreased! drug doses have to be adjustedKidney 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

TÁMOP /1/A hypertensionAtrophy of renal parenchyma + sclerotic a. renalis  regulation of blood pressure defective, tendency for hypertension, but hypovolemia may cause hypotension. anemia.Erythropoietin deficiency due to reduced renal parenchyma and gonadal hormon secretion  anemia. senile osteoporosisActive D-vitamin formation decreases  bone abnormalities (senile osteoporosis). Aging vs. non-excretory kidney functions

TÁMOP /1/A 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 incontinenceUrinary incontinence (The capacity of the urinary bladder reduces which leads to frequent urination.) Urinary infectionsUrinary infections Benign prostatic hyperplasia, prostate cancer Atrophic vaginitis

TÁMOP /1/A Renal failure in the elderly: causes acute renal failure 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 renal failure Chronic ischemic renal disease and progressive damage of the renal parenchyma lead to chronic renal failure. Risk factors: diabetes mellitus hypertension hyperlipidemia obesity

TÁMOP /1/A Renal failure in the elderly: dialysis and kidney transplantation diabetic nephropathy renovascular diseases 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. limiting factor for kidney transplantation multimorbidity The only limiting factor for kidney transplantation is the presence of multimorbidity (hypertension, DM, significant atherosclerosis).

TÁMOP /1/A Urinary tract infection Symptoms: 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: Pathogens: E. Coli, Enterococci, Streptococci, Proteus. Treatment: Treatment: oral rehydration, frequent urination, selected antibiotics, roboration.

TÁMOP /1/A IncontinenceDefinition: Involuntary loss of urine through the urethra.Types: functional, stress, urge, reflex, overflow.

TÁMOP /1/A 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.

TÁMOP /1/A 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.

TÁMOP /1/A Urge/reflex incontinence Sudden, unexpected urge to void after certain stimuli.Causes: cystitisatrophic 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).

TÁMOP /1/A Overflow incontinence Unexpected urine loss from the overfilled bladder.Causes: benign prostatic hyperplasiabenign 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).