The Kidneys and Urinary Tract

Medicine for students in technology and science

MFEL 3010

Stein Hallan, MD PhD Dept. of Nephrology. St. Olav Universtiy Hospital

Overview n  3 lectures covering

n  Anatomy / physiology / diagnostic tools

n  Diseases

n  Dialysis

2 kidneys""

2 ureteres""""

1 bladder""

1 uretra"

Urinary tract

Tasks

n  Kidneys n  Remove waist products from the blood n  Remove water n  Produce hormons

n  The rest n  Transport the urine produced in the kidney

out of the body

Anatomy

The kidneys and its nabour organs, seen form the front

Anatomy

Position of the kidneys under the lower ribs and muscles, seen from behind

Anatomy

Cross section showing the kidneys, spleen, stomach and liver (seen from above )

Anatomy

Kidney with its capsule, artery, vein and ureter

Anatomi

Cortex vs marrow, pyramides, collection system, fat.

Anatomy

Arterial supply

Anatomy

Urinary bladder, prostate, uretra

Anatomy

2 nephrons: arteriole, glomerulus, tubulus, collecting ducts

Cortex Marrow Tip of pyramide

Anatomy

Drawing of the Glomerulus

Blood

Urine

Capillaries (small blood vessels)

Anatomy

Glomerulus Scanning Electron Microscope, 1000 x

Anatomy

Glomerulus, vessels, tubulus Seen with a light- microscope, 400 x

Anatomy

Anatomy

The border beween the blood and the urinary space. Elektronmikroskop, 50000 x

Physiology

Water reabs.

Biochemical tests

n  Autoanalyzers n  Fully automatic n  High throughput n  Very precise results n  Low price per test

Biochemical tests for the kidney

n  Blood (hematology) n  Hemoglobin (Hb) n  Leucocytes (white) n  Trombocytes

(platelets) n  Electrolytes

n  Na n  K n  Ca n  Phosphate

n  Kidney function n  Creatinine n  Carbamide (urea)

n  Other n  Albumine n  Bicarbonate

n  Urine n  Stix n  Culture (bacterial)

Biochemical tests n  Hematology

n  Flowcytometer n  Single cells are examinded

with n  Laser n  Current / resistance n  Staining

n  1000s of cells are characterised regarding

n  Size n  Nuclear size n  Granularity n  Enzyme content

Biochemical tests

n  Hematology n  Microscopy

n  Red blood cells n  2 different white

blood cells (leucoc.) n  1 platelet

(trombocyte)

Imaging of renal disorders

n  X-ray (± contrast medium) n  Ultrasound n  CT / MR n  Angiography n  Nuclear medicine

Imaging

X-ray without contrast: Many big kidney stones

Imaging

X-ray with iv contrast (urography): Normal

Imaging

Ultrasound: Kidney with dilated renal pelvis due to obstruction Problems: low picture quality, time consuming, highly operator dependent.

Imaging

Ultrasound: Kidney with 2 stones giving shaddows

Imaging

Computer Tomography (cross sections through the kidneys, seen from below): Right: normal Left: reduced contrast enhancement, increased size, hematoma under the capsule after car crash Problems: High radiation dose, contrast toxicity

Imaging

Angiography: Normal. Catether seen at top Problems: Expencive, high contrast dose, embolism (blood clots), radiation

Imaging

Angiography: No kidney on right side, very narrow lumen (stenosis) in left artery. Dilated during the same procedure

Imaging

CT Angiography: (non-invasive, computerbased reconsstruction of vessels and organs containing contrast)

Common Diseases

n  Urine infection n  Prostate

n  Benign enlargement n  Cancer

n  High blood pressure n  Kidney stone n  Chronic kidney failure

n  Dialysis n  Transplantation

Urinary Tract Infection

n  Bacteria n  Gram neg. rods n  E.Coli, Klebsiella,

Proteus, etc n  Natural inhabitants

n  Gut n  Skin

n  Defence mechanism n  Flowing fluids n  Mechanical barriers n  Cells

UTI - symptoms

n  Lower n  ”Cystitis” n  No fever n  Burning, pain, smell,

frequent voiding n  Not dangerous

n  Upper n  ”Pyelonephritis” n  Fever n  Pain in back,

shivering, nausea, n  Dangerous n  Needs antibiotic,

sometimes hospitalization

UTI- evaluation and treatment

n  Urine n  Dipstic (red and

white cells, bacteria) n  Culturing

n  Type n  Effect of antibiotics

n  Imaging n  Obstruction n  Reflux

n  Antibiotics n  Penicillins

n  Ampicillin n  Selexid

n  Cefalosporins n  Aminoglykocids n  Trimetoprim, Sulfa

n  Supportive treatment n  IV fluids n  BP-increasing drugs n  Oxygen n  etc

Prostate - enlargement n  Common

n  Frequencey (%)= age

n  Diffuse enlargement n  Not cancer n  Nodules (soft) n  Increased outflow

resistance from bladder

n  Symptoms n  Frequent voiding n  Nocturia n  Difficult to start or stop n  Sometimes without

symptoms

Normal 20 gr

Prostate - enlargement

n  Complikations n  UT infections n  Kidney failure

n  Treatment n  Bladder catheter

n  Permanent n  Intermitterent

n  TURP n  Other

n  Local heating n  Drugs Bladder: dilated and with

increased muscle trabecles

Prostate - cancer

n  Common n  20% of all men n  Many dies with

and not due to the cancer

n  Harde nodules

n  Reasons n  DNA damage n  Testosteron-

dependent The tumor is composed of small glands that are lined by a single layer of hyperchromatic cells. In contract to normal glands, which have two layers, these neoplastic glands have only one layer and abut directly onto the interstitial connective tissue. A normal

prostatic duct appears at the far right.

Prostate - cancer

n  Symptoms n  Local

n  Obstruction n  Blood in urine

(seldom)

n  Metastases n  Bone pain

n  Treatment n  Curative

n  Prostate removal n  Radiation of prostate

n  Palliative n  TURP n  Castration (- testo)

n  Surgical n  Drugs

n  Radiation of bone lesions

n  X-ray n  Radioactive

isotopes

High blood pressure

140 cm water / blood column

10 cm (100 mm) Mercury (Hg)

High blood pressure: frequency

Hypertension: ”in the old days”

n  US-president Roosevelt n  1938: 170/90, - sympt n  1941: 185/105 n  1943: 200/110, heart +

kidney failure n  1945: died of bleeding in

brain

n  Treatment: n  rest, saltrestriction,

sedativa

n  Loss of years (untreated)

M 35 M 45 M 55

Normal 42 32 23

130/90 -4 -3 -1

140/95 -9 -6 -4

150/100 -16.5 -11.5 -6

Hypertension: complications

….no critical border, but a continuum …

Hypertension: lifestyle modificatons

Hypertension: drug treatment

n  Reduction of pressure n  8-15 mm Hg reduction

for most drugs

n  Effect on clinical endpoints n  30-40% red. of stroke n  20% red. of heart

infarction

Kidney stones

n  Frequent disease n  Causes

n  Super-saturation of urine

n  Calciumfosfat n  Caliciumoxalat n  Fosfat / infection n  Urate

n  Size n  1-80 mm. n  < 6-7 mm will pass

Kidney stones

n  Symptoms n  Very severe pain n  Colic type, radiating

to groin n  Blood in urine

n  Examinations n  X-ray

n  Stone n  Passage of urine

n  Complications n  Infection n  Acute kidney failure n  Chronic kidney

failure

Kidney stones: treatment

n  Fragmentation n  Extracorporal shock

waves n  Laser / US directly

on stone

n  Removal n  Laparascopy n  Ureteroscopy

Chronic kidney disease n  Frequency

n  Mild: 5% n  Serious: 0.5% n  Dialysis: 0.1%

n  Progressive n  Lifelong

n  Causes n  Kidney inflammation n  Diabetes n  High blood pressure n  Atherosclerosis n  Cystic diseases (genetic) n  Infection / stone n  Obstruction n  other

n  Cancer n  Drugs n  Inflammation in vessels

Kidney failure (CKD stage 5) n  Symptoms

n  None at mild – moderate disease (stage 1,2,3 (4))

n  Fatigue, lethargy n  Nausea, vomiting n  Anorexia, loss of muscle

mass n  Itching

n  Complications n  Cardiovascular disease

n  Heart infarction, angina n  Stroke n  Heart failure

n  Anemia n  Bone disease n  Infections n  Other

n  bleeding n  Nerve damage n  Red fertility and sex

drive

Kidney failure n  Evaluation

n  Blood tests n  Hb n  Na, K, Ca, Fosfat n  Creatinine n  Blood sugar, cholesterol

n  Urine n  Protein

n  Ultrasound ex of kidney n  Size n  Obstruction n  Scarring

Glomerular Filtration Rate (ml/min/1.73m2)

200150100500

s-C

reat

inin

e (m

ikro

mol

e/lit

re)

1000

800

600

400

200

0

Kidney failure: treatment

n  Mild - moderate n  Reduce BP n  Reduce u-protein n  Strict blood sugar

control n  Correction of

n  Low hemoglobin (Epo)

n  High phosphate n  High potassium n  Acid retention n  Low calcium

n  Serious n  Dialyse n  Transplantation

Renal replacement therapy

Renal replacement therapy in NorwayStatus by end of year - pats. pr mill. inhabitants

0

20

40

60

80

100

120

140

160

180

82 84 86 88 90 92 94 96 98 100 102TL 05 /03

In dialysis

New in RRT

Tx performedWaiting list

00 02

Dialysis

Hemodialysis Peritoneal dialysis

n  Semipermeable membrane

n  Diffusion of small molecules

n  Convection of medium molecules

n  Ultrafiltration of water

Filter Dialysis fluid l High/low patassium l High/low calsium l Bicarbonate

The hemodialysis machine

Dialysis water

n ”Standard-HD-pas” is exposed to 0,5 l/min x 4 h x 3 x 52 = 18 720 l/yr In the early days of dialysis treatment problems with Al. Bacteria and endotoxins: stimulation of inflamation, decreased response of erythropietin and possibly aggravation of atherosclerosis.

Blood access Two lumen large bore catheter in neck vein with subcutanous tunnelation

Can be used 6-8 weeks after the operation

Arterio-venous fistula («short-cut»)

n  ”Needles were the worst thing I could think about, so I never thought I could do this myself. But now, nobody else is allowed to get near my arm……..”

How much dialysis is enough?

Kidney transplantation

n  Necro donation n  Traffic accidents,

cerebral bleedings n  Waitinglist 1-2 years

n  Living donation n  Parents, siblings,

children n  Spouse, good friend n  40 % of all Tx in

Norway n  Waitinglist 2-3

months n  Better survival of the

new kidney

1 2 3 4 5 6 7 8

10

20

30

405060

70

80

90100

Graf

t Sur

viva

l %

CD; 1-2 DR mm. N=479

CD; 0 DR mm. N=301LD; non-id. N=738

LD; HLA-id N=101

Years

LD (N=839) vs. CD (N=780): p= 0.0016LD non-id. vs. CD 0 DR mm. : n.s. (p= 0.2157)LD non-id. vs. CD 1-2 DR mm. : p < 0.0001CD 0 DRmm. vs. CD 1-2 DR mm.: p < 0.0001

First renal graft survival in patients below 60y.By donor source and HLA match

Norway 1989-2002

n  Surgery n  ”Medium operation” n  Low risk of death

n  Immunosupression n  Prednisolon n  Cyclosporin n  Cytostaticum

n  Acute complications n  Acute rejection n  Urine leakage, bleeding,

clotting of vessel n  Infection in wound, urine,

lungs, sepsis (”blood poisioning” )

n  Benefits over dialysis n  Cheaper n  Much better quality

of life n  Better survival n  Less cardiovascular

complications

n  Complications n  Infections n  Loss of transplant

function n  Cardiovascular

disease n  Cancer

Prednisolon n  Antiinflammatory + immunosupressiv effect n  Reduced the production of many cytokines

40 mg x1 reduced to 5 mg x 1

2.CD28 1.TCR+CD3

Ag

CNI

Calcineurin inhibitors cyclosporin A

Imurel

n  Interfers with DNA synthesis. Built into DNA- og reduces celleproliferation

n  Nobel prize 1988

Halloran P. N Engl J Med 2004; 351:2715-29

0 12 24 36 48 60 72 84 96 108 120

10 20 30 40 50 60 70 80 90

100

Months

Gra

ft S

urvi

val %

Survival of first CD renal grafts

1992-97

1978-82

1987-91

1983-87

TL

Summary

n  Kidney and urinary tract diseases include n  Very frequent and very seldom diseases n  Acute and chronic, harmless and deadly n  Strong dependence of technical solutions for

evaluation and treatment n  Great challenges in the time to come