introduction to nephrology pdf - د. محمد حنون

محمد حنون

Nephrology

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Nephrology

Introduction to

nephrology

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محمد حنون

Nephrology

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محمد حنون

Nephrology

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Introduction To Nephrology

Anatomy of the kidneys

Kidneys are two bean shaped organs ,retroperitoneal , on either side of the aorta and
inferior vena cava.

Two kidneys , about 2 million glomerular capillary tuft .

Each kidney is about 150 g ,

11–14 cm in length ( =3 lumbar vertebral bodies),

The Rt kidney is usually a few cm lower ( the liver lies above it).

Rise and descend several centimeters with respiration.

Each kidney contains 1 million functional units, ‘nephrons’.;-

The Glomerulus

(where filtration of plasma occurs),

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Nephrology

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The tubules

Proximal convoluted, loop of Henle and distal convoluted tubule (where selective re
absorption of fluid & solutes),

Collecting ducts

of multiple nephrons drain into the renal pelvis and ureters

150 L daily filtrate

99% is reabsorbed in the tubules.

After birth, new nephrons can not be developed ,a lost nephron can not be replaced

Renal blood flow

The blood supply ; 20–25% of cardiac output.

Aorta  Renal artery  interlobar arteries 
interlobular arteries 

afferent arterioles  glomerulus  efferent arterioles

In the cortex  peritubular capillaries

In the juxtamedullary region vasa recta

Back to the heart through the interlobular  intralobar  renal veins

Kidney structure

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Nephrology

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Anatomy of the kidneys :-

Glomeruli

Glomerular basement membrane(GBM), produced by fusion of the BM of

epithelial and endothelial cells . Filtration occurs across GBM

-The glomerular capillary endothelial cells contain fenestrae (pores) which allow access
of circulating molecules to the underlying GBM.

- On the outer side of the GBM, glomerular epithelial cells (podocytes) put out multiple
long foot processes which interdigitate with those of adjacent epithelial cells
maintaining the filtration barrier,

Podocytes are involved in the regulation of filtration

Mesangial cells

lie in the central region of the glomerulus. have contractility function

with macrophage-like properties.

Electron micrograph of the filtration barrier. (GBM = glomerular basement membrane)

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Nephrology

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Anatomy of the kidneys :-

Tubules and interstitium

Tubular cells are polarised, with a brush border (proximal tubular cells) and specialised
functions at both basal and apical surfaces. carry a specific complement of transporter,
channel and receptor molecules.

Fibroblast-like cells

in the cortex produce erythropoietin in response to hypoxia.

Collecting system and lower urinary tract

Allow free passage of urine to the bladder, and to store urine in the bladder for
controlled voiding (i.e. to maintain urinary continence).

Processes Occurring Along the Nephron

Site Absorption Secretion

PCT Na+, HCO3– Organic acids

glucose, amino acids,

phosphates, vitamins

Thick Ascending Na+, K+, Cl–

Limb of Loop of Henle

DCT Na+, Cl– H+, K+

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Nephrology

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Anatomy of the kidneys

Juxtaglomerular (J-G) apparatus

adjacent to glomerulus where afferent arteriole enters

consists of myoepithelial cells - modified granulated smooth muscle cells in the media
of the afferent

arteriole that contain renin

macula densa - specialized region of the distal tubule which controls renin release

↓GFR  Renin

Angiotensin

Blood Pressure

JGA

Renin Angiotensin Axis

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Functions of the kidneys

Regulating the volume and composition of body fluids

large volumes of an ultrafiltrate of plasma (120 mL/min, 170 L/day) glomerulus,

selectively reabsorbing components of this ultrafiltrate at points along the nephron.
controlled by many hormonal and haemodynamic signals.

Excretion of many metabolic breakdown products

Ammonia, urea and creatinine from protein,

Uric acid from nucleic acids .

Drugs and toxins.

Not reabsorbed from the filtrate, or are actively secreted into it.

Functions of the kidneys

ENDOCRINE FUNCTION

OF THE KIDNEY

Erythropoietin

hormone produced by kidneys (& liver) in response to hypoxia

stimulates erythrocyte production and maturation produced by fibroblast-like cells
(peritubular) in cortical interstitium

responds in 1.5 to 2 hours

in renal disease anemia results from decreased renal capacity for

Epo production and release, as well as decreased red blood cell life

span (toxic hemolysis

Vitamin D acivation

25-hydroxycholecalciferol to the active form, 1,25- dihydroxycholecalciferol vitamin D is
converted to the 25-hydroxy-vitamin D form in the liver. the kidney converts 25-hydroxy-
vitamin D to 1,25-dihydroxy-vitamin D

in renal disease this capacity becomes impaired and contributes to the tendency
towards hypocalcemia and subsequent secondary hyperparathyroidism (since 1,25-
dihydroxy-Vitamin D is necessary for intestinal calcium absorption)

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Functions of the kidneys;-

Renin

secreted from the juxtaglomerular apparatus in response to;-

reduced afferent arteriolar pressure,

stimulation of sympathetic nerves

changes in Na

content of fluid in the DCT at macula densa.

Renin generates angiotensin II , which causes

aldosterone release from the adrenal cortex,

- constricts the efferent arteriole of the glomerulus and thereby increases glomerular
filtration pressure

induces systemic vasoconstriction.

Investigation of renal and urinary tract diseases

Serum levels of endogenous compounds excreted by the kidney

Blood urea

it increases - with high protein intake + GIT haemorrhage

catabolic states,

Normal RF

Renal failure

Regulatory &Exretory

functions

Erythropietein

Vit D Activation

Renin

HrT ,fluid overload ,

,Acidosis, Uremia

Anemia

HrT

Hypo Ca++

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it reduced - liver failure (low production from protein)

anorexia or malnutrition (low protein intake).

tubular reabsorption of urea is increased when concentrated urine is produced,
elevating blood levels..

Serum creatinine

Reflects GFR more reliably than urea,

it is produced from muscle at a constant rate

almost completely filtered at the glomerulus.

While in patients with low muscle mass (e.g. the elderly) serum creatinine may not be
above normal until GFR is reduced by > 50%.

Serum creatinine and GFR

The inverse reciprocal relationship

a GFR as low as 30–40 mL/min without serum creatinine rising

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Nephrology

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Investigtion of renal and urinary tract diseases

Glomerular filtration rate (GFR)

GFR is the rate at which fluid passes into nephrons after filtration

measures renal excretory function.

proportionate to body size ( 120 ± 25 mL/min/1.73 m2 )

Direct measurement of GFR

•

1. Direct measurement using labelled EDTA or Inulin

by injecting and measuring the clearance of compounds that are completely filtered and
not reabsorbed by the nephron (inulin, radiolabelled EDTA) is inconvenient and is
usually reserved for special circumstances (e.g. for potential live kidney donors).

. Creatinine clearance(CrCl)

A more accurate measurement of GFR

Serum level is related to 24-hour urinary creatinine excretion,

But 24-hour urine collections are difficult and often inaccurate.

Minor tubular secretion of creatinine causes exaggerate

- GFR affected by drugs (e.g. trimethoprim, cimetidine)

Needs 24-hr urine collection (inconvenient and often unreliable)

CrCl (mL/min) = UV / P / 1440 =

Urine creatinine concentration (μmol/L) × Volume (ml)
__________________________________________________

Plasma creatinine concentration (μmol/L) × time (min

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Estimating GFR with equations

Cockcroft and Gault (C&G) equation

-accurate at normal to moderately impaired RF

-Estimates CrCl, not GFR ,Requires patient weight

CrCl (C&G) =

(140–age in yrs) × lean body wt (kg) × (1.22 males or 1.04 females)

_________________________________________________________ serum
creatinine (μmol/L)

CrCl (C&G) =

(140–age in yrs) × lean body wt (kg)

___________________________________ ( x 0.85 for females)

72 X serum creatinine (mg/dl)

Estimating GFR with equations

The Modification of Diet in Renal Disease (MDRD) study equation The MDRD equation

Performs better than C&G at reduced GFR

Requires knowledge of age and sex only

Can be reported automatically by laboratories

eGFR = 186* × (creatinine in μmol/L/88.4)− 1.154 × (age in yrs) −0.203× (0.742 if female)
× (1.21 if black)

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Nephrology

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Urinalysis

detect abnormal constituents that indicate a pathological state.

General characteristics of urine

1. Volume: normally 1.5– 2 L / Day.

2. Color: urochrome (amber yellow).

3. Transparency: Clear transparent.

4. Odor: faint aromatic odor (volatile organic acid)

5. PH : slightly acidic 5.5 – 6.5.

Physiological and normal constituents of urine

Normally 99 % water and 1% solids. Solids are:

organic substances: urea, uric acid, creatine, creatinine,

amino acids, lactic acid , vitamins, pigments, enzymes……

inorganic substances: NH4, SO4, Ca+2, Cl-, PO4, Co3,

Na+, K+, Mg+2, NO3, Fe, F, silicate…………….

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Nephrology

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Urinalysis

The following parameters are normally not present in urine:

Glucose: (glucosurea),

Protein: (proteinurea or albuminurea)

Blood: (hematurea or hemoglobinurea)

Bile salts: in patients with Jaundice.

Ketone bodies or Acetone: could appear in urine in late stages of diabetes mellitus

Urinalysis



Dipsticks

screen for blood and protein semi-quantitatively



Urine microscopy

;-red cells of glomerular origin and red cell casts, indicative of

intrinsic renal disease.



screen for white blood cells and bacteria.



Crystals

(e.g. of calcium oxalate, cysteine or urate)

seen in renal calculus disease, although calcium oxalate and urate crystals are also
sometimes found in normal urine that has been left to stand.



Urine pH

can provide diagnostic information of of RTA persistently



low specific gravity

may be found in diabetes insipidus).



Timed (usually 24-hour) urine collections

are now used less often to measure GFR or

protein excretion but are still required to measure excretion rates of sodium and of
solutes that can form renal calculi such as calcium, oxalate and urate .

Urinalysis

Fractional excretion of sodium

(= urinary Na/plasma Na × plasma creatinine/urine

creatinine) is reduced in volume depletion when the

tubules are avidly conserving sodium, and increased

in the tubular damage associated with acute tubular necrosis