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Introduction To Nephrology

Dr. Mohammed Hannon Al Sodani C.A.B.M., F.I.B.M Consultant Nephrologist. Lecturer , College of Medicine, Baghdad University 5th year medial student March 7th,2016

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.

Anatomy of the kidneys ;-

Anatomy of the kidneys ;-

Anatomy of the kidneys ;-

Each kidney contains 1 million functional units, ‘nephrons’.;- - The Glomerulus (where filtration of plasma occurs), - 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 arteriolesIn the cortex  peritubular capillariesIn the juxtamedullary region vasa rectaBack to the heart through the interlobular  intralobar  renal veins


Kidney structure


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.
Anatomy of the kidneys ;-

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+

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

* JGA

↓GFR  ReninAngiotensinBlood Pressure MD consult

Renin Angiotensin Axis

Renal Lecture Required Picture #4

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)
Functions of the kidneys;-

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.

Renin Angiotensin Axis

Normal RF Rena Failure
HrT
Hypo Ca++
Anemia
HrT ,fluid overload , ,Acidosis, Uremia
Regulatory &Exretory functions
Erythropietein
Vit D Activation
Renin

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, 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..

Investigation of renal and urinary tract diseases

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

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).

2. Creatinine clearance(CrCl) A more accurate measurement of GFRSerum 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) Ч Volume (ml) __________________________________________________ Plasma creatinine concentration (μmol/L) Ч time (min .

Estimating GFR with equations

Cockcroft and Gault (C&G) equation;--accurate at normal to moderately impaired RF-Estimates CrCl, not GFR ,Requires patient weightCrCl (C&G) = (140–age in yrs) Ч lean body wt (kg) Ч (1.22 males or 1.04 females)_________________________________________________________ serum creatinine (μmol/L) CrCl (C&G) = (140–age in yrs) Ч 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 equationPerforms better than C&G at reduced GFRRequires knowledge of age and sex onlyCan be reported automatically by laboratorieseGFR = 186* Ч (creatinine in μmol/L/88.4)− 1.154 Ч (age in yrs) −0.203Ч (0.742 if female) Ч (1.21 if black)

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…………….

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

Imaging Techniques
Plain X-rays ; - renal outlines - opaque calculi - calcification within the renal tract. Ultrasound - This quick, non-invasive is the first and often the only. - renal size and position, - detect dilatation of the collecting system ( obstruction) - distinguish tumours and cysts. - the prostate and bladder, and estimate completeness of emptying - other abdominal, pelvic and retroperitoneal pathology. - In CKD ,U/S density (echogenicity) of the renal cortex is increased and cortico-medullary differentiation is lost.

Normal kidney. The normal cortex is less echo-dense (blacker) than the adjacent liver.

A simple cyst occupies the upper pole of an otherwise normal kidney.



The renal pelvis and calyces are dilated by a chronic obstructionto urinary outflow. The thinness and increased density of the remaining renal cortex indicate chronic changes


Doppler techniques - show blood flow in extrarenal & larger intrarenal vessels. -The resistivity index is the ratio of peak systolic and diastolic velocities, and is influenced by the resistance to flow through small intrarenal arteries. may be elevated in various diseases, - acute glomerulonephritis - rejection of a renal transplant. High peak velocities - severe renal artery stenosis. However, renal ultrasound is;- - operator-dependent, - stored images convey only a fraction of the information - it is often less clearin obese patients
Imaging Techniques

Imaging Techniques

Intravenous urography (IVU) ;- X-rays taken at intervals following administration of an IV bolus of an iodine-containing compound that is excreted by the kidney. An early image (1 minute after injection) demonstrates the nephrogram phase of renal perfusion followed by contrast filling the collecting system, ureters& bladder. An excellent definition of the collecting system and ureters, Superior to U/S for examining renal papillae, stones & urothelial malignancy The disadvantages of this technique are the injection of a contrast medium, exposure to irradiation , time requirement, dependence on adequate renal function,

Imaging Techniques

Pyelography direct injection of contrast medium into the collecting system from above or below. best views of the collecting system and upper tract, used to identify the cause of urinary tract obstruction). Antegrade pyelography requires the insertion of a fine needle into the pelvicalyceal system under ultrasound or radiographic control. difficult and hazardous in a non-obstructed kidney. In the presence of obstruction, percutaneous nephrostomy drainage can be established, and often stents can be passed through any obstruction. Retrograde pyelography can be performed by inserting catheters into the ureteric orifices at cystoscopy.


Intravenous urography (IVU). A Normal nephrogram phase at 1 minute. B Normal collecting system at 5 minutes. C Bilateral reflux


Retrograde pyelography.. A catheter has been passed into the left renal pelvis at cystoscopy. The anemone-like calyces are sharp-edged and normal

Imaging Techniques

Renal arteriography and venography to investigate suspected renal artery stenosis or haemorrhage. Therapeutic balloon dilatation and stenting of the renal artery bleeding vessels or arteriovenous fistulae occluded. Computed tomography (CT) characterizing masses & cystic lesions within the kidney clear definition of retroperitoneal anatomy regardless of obesity. Even without contrast medium it is better than IVU for demonstrating renal stones. In CT urography, after a first scan without contrast, scans are repeated during nephrogram and excretory phases. This gives more information but entails a substantially larger radiation dose than IVU



CT, the Rt kidney is expanded by a low-density tumour which fails to take up contrast material. Tumour is shown extending into the renal vein and inferior vena cava .

Imaging Techniques

. CT arteriograms are reconstructed using a rapid sequence technique in which images are obtained immediately following a large bolus injection of intravenouscontrast medium. This produces high-quality images of the main renal vessels and is of value in trauma, renal haemorrhage and the investigation of possible renal artery stenosis. - enables functional assessment of vascular structures, e.g. angiomyolipomas. However, relatively large doses of contrast are required


. Imaging Techniques Magnetic resonance imaging (MRI) excellent resolution and distinction between different tissues A Normal kidneys. B Polycystic kidneys;.

Magnetic resonanceangiography (MRA) uses gadolinium-based contrast media, which may carry risks for patients with very low GFR . good images of main renal vessels but may miss branch artery stenosis
Renal artery stenosis. MRA following injection of contrast. The abdominal aorta is severely irregular and atheromatous. The left renal artery is stenosed

Radionuclide studies;-

- A functional studies requiring the injection of gamma ray-emitting radiopharmaceuticals which are taken up and excreted by the kidney, monitored by an external gamma camera. (99mTc-DTPA) Diethylenetriamine-pentaacetic acid labelled with technetium is excreted by glomerular filtration. provides information regarding the arterial perfusion of each kidne Delayed peak activity and reduced excretion is seen in RAS. In patients with significant obstruction of the outflow tract, DTPA persists in the renal pelvis, and a loop diuretic fails to accelerate its disappearance.

Radionuclide studies;-

(99mTc-DMSA) technetium labelled Dimercaptosuccinic acid is filtered by glomeruli and partially bound to proximal tubular cells. Following intravenous injection, images of the renal cortex show the shape, size and relative function of each kidney. sensitive method for showing cortical scarring that is of particular value in children with vesico-ureteric reflux and pyelonephritis.

Renal complications of radiological investigations

Contrast nephrotoxicity ;-An acute deterioration in renal function, commencing < 48 hrs after of i.v. radiographic contrast mediaRisk factors- Pre-existing renal impairment - Use of high-osmolality, ionic contrast media and repetitive dosing in short time periods Diabetes mellitus MyelomaDehydartion – Drugs ACEI ARBs NSAIDs


Contrast nephrotoxicity ;-
Prevention•• If the risks are high, consider alternative methods of imaging- Hydration, e.g. free oral fluids plus i.v. isotonic saline 500 mLthen 250 mL/hr during procedure- Avoid nephrotoxic drugs; withhold (NSAIDs). Omit metformin for 48 hrs after procedure in case renal impairment occurs- N-acetyl cysteine may provide weak additional protection

Cholesterol atheroembolism

Days to weeks after intra-arterial investigations or interventions. caused by showers of cholesterol-containing microemboli, arising in atheromatous plaques in major arteries. in patients with widespread atheromatous disease, usually after interventions such as surgery or arteriography but sometimes after anticoagulation. loss of renal function, haematuria ,proteinuria, eosinophilia and inflammatory features ( mimic a small-vessel vasculitis.) Accompanying signs of microvascular occlusion in the lower limbs (e.g. ischaemic toes, livedo reticularis) are common There is no specific treatment but anticoagulation may be detrimental.


The foot of a patient who suffered extensive atheroembolism following coronary artery stenting.

Renal complications of radiologicalinvestigations

Nephrogenic sclerosing fibrosis after MRI contrast agents - Chronic progressive sclerosis of skin, deeper tissues and other organs, associated with gadolinium-based contrast agents • Only reported in patients with renal impairment, typically on dialysis or with GFR < 1mL/min/1.73m2. caution is advised in patients with GFR < 30 mL/min/1.73m2

Renal biopsy;-

Renal biopsy is used to establish the nature and extent of renal disease in order to judge need for treatment & the prognosis. Transcutaneous, with U/S or contrast radiography guidance to ensure accurate needle placement into a renal pole. -Specimens are divided into 3 samples and placed in - formalin for light microscopy, - normal saline for subsequent snap-freezing in liquid nitrogen for immunofluorescence, glutaraldehyde for electron microscopy -.

Renal Biopsy ;- Indications

• ARF , not adequately explained (after exclusion of obstruction, reduced renal perfusion and ATN .• CKD with normal-sized kidneys or unexplained ,may be diagnostic, (e.g., identify IgA nephropathy )• Nephrotic syndrome or glomerular proteinuria in adults• Nephrotic syndrome in children with atypical features or is not responding to treatment• Isolated haematuria • Non Nephrotic range proteinuria >1g/24hr with renal characteristics or associated abnormalities • Familial Renal Disease Biopsy of one affected member • Renal Transplant Dysfunction .

Renal biopsy;-Contraindications

Pateint related ;- - Disordered coagulation or thrombocytopenia. Aspirin and other antiplatelet agents increase bleeding risk- Uncontrolled hypertension - Uremia - Obesity - Uncooperative patient• Kidney related- Kidneys < 60% predicted size- Solitary kidney (except transplants) (relative contraindication)-Acute pyelonephritis/ perinephric abscess -Renal neoplasmMost contraindications are relative rather than absolute; when clinical circumstances necessitate urgent biopsy, they may be overridden, apart from uncontrolled bleeding diathesis.


Renal Biopsy;- Complications;-
• Pain, usually mild• Bleeding into urine hematurea , usually minor / clot colic and obstruction• Bleeding around the kidney hematoma, occasionally massive and requiring angiography with intervention, or surgery• Arteriovenous fistula, rarely significant clinically

Hematurea

Haematuria ;- indicates bleeding from anywhere in the renal tract. macroscopic;- - visible and reported by the patient - tumors (most). - severe infections or -renal infarction usually accompanied by pain. microscopic ;- invisible and detected on dipstick testing of urineMicroscopy shows that normal individuals have occasional red blood cells (RBC) in the urine (up to 12 500 RBC/mL). The detection limit for dipstick testing is 15–20 000 RBC/mL,. However, dipstick tests are also positive in the presence of free haemoglobin or myoglobin.

Interpretation of dipstick-positive haematuria

Urine microscopy Suggested cause --------------------------------------------------------------------------------------------------- - Menstruation, strenuous exercise, Haematuria - White blood cells - Infection - Abnormal epithelial cells - Tumour - Red cell casts with Dysmorphic RBC Glomerular bleeding ------------------------------------------------------------------------------------------------ Haemoglobinuria No red cells Intravascular haemolysis ----------------------------------------------------------------------------------------------- Myoglobinuria (brown urine) No red cells Rhabdomyolysis

Dipstick test negative Urine

Cause Urine colour Food dyes Acanthocyanins (beetroot) Red Drugs Phenolphthalein Pink when alkaline Senna/other anthaquinones Orange Rifampicin Orange Levodopa Darkens on standing Bilirubinuria e.g. Obstructive jaundice Dark Dipstick +ve bilirubin, - - ve haemoglobin Porphyria Darkens on standing Alkaptonuria

Glomerular bleeding

Glomerular bleeding is characteristic of ;- inflammation destruction degeneration these processes disrupt the glomerular basement membrane (GBM) to cause microscopic or macroscopic haematuria

Approach to haematuria

Haematuria( repeated ) exclude menstruation infection, traumaIf RBC confirmed on urine microscopy, infection absent on cultureRenal imaging ? anatomical lesion: renal U/S, IVU & cystoscopy + ve Full assessment & Mx (Urology/Oncology) If - ve :-Are there features of significant renal disease? e.g. Proteinuria HrT, Abnormal RFT Family Hx ?? Systemic dis. Yes Consider renal biopsy No Observation (Urine test, BP, creatinine ) 6 – 24 months Re-refer if anything changes




رفعت المحاضرة من قبل: AyA Abdulkareem
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