Renal- Structure and Function

Kidney weight and position

Adult kidney 120-170 g;
Right kidney slightly lower than left kidney
Kidneys are retroperitoneal; neither kidney is normally palpable. The kidneys are contained posteriorly by the psoas muscles.

Renal blood flow and nervous system

Blood carried to the kidney by the renal artery and taken away by the renal vein.
-Renal blood Flow: 1/5 of the cardiac output; RBF approx. 1200 ml/min, renal plasma flow about 600 ml/min.
-Modulated by hormones and autocrine factors (thromboxanes, endoth

Kidney structure

Two distinct regions: outer cortex and inner medulla. Medulla contains 6-15 pyramids, which drains into the minor calices
Cortex: Glomeruli
Medulla: Renal tubules (with calyces forming the medulary pyramids)
Ureter: Takes urine to bladder; Posterior to an

Nephron components

Glomerulus (filtering)
-Endothelial cells
-GBM glomerular basement membrane
-Epithelial cells
-Mesangial (supporting cells)
Tubule:
-Proximal
-Loop of Henle
-Distal convoluted
-Collecting duct

Function of glomerulus
Glomerular basement membrane:

Primary function of glomerulus is ultrafiltration of plasma, producing an iso-osmotic cell-free filtrate that passes into Bowman's space.
-Nonselective filter for plasma substances with MW <70,000
Glomerular Basement Membrane: acellular layer of hydrated

Epithelial Cells:
Mesangial cells:

Epithelial Cells:
-Visceral epithelial cells (podocytes) are largest cells in glomerulus; negative surface charge due to sialoproteins
-Parietal epithelial cells form outer wall of Bowman's capsule
Mesangial cells: supporting cells; have actin-myosin elem

Glomerular filtration barrier

consists of two layers of cells: endothelial cells and visceral epithelial cells (podocytes), with the glomerular basement membrane

Renal blood flow and renal plasma flow

Renal Blood Flow: 1200 ml/min, approx. one-fifth of cardiac output
Renal Plasma Flow: 600 ml/min

Filtration fraction

Filtration Fraction: percentage of renal plasma flow that is filtered:
-FF= GFR/RPF (normally about 20%)

GFR

GFR: results from outwardly directed net pressure that moves fluid across semipermeable capillary wall: 120 mL/min
GFR = Kf (P-) Starling Equation
Normal GFR 120 ml/min or 180 L/day filtrate; of this 178.5 L (99%) reabsorbed

Autoregulation

RBF and GFR are maintained at constant levels over a wide range of arterial pressures between 70-180 mm Hg.
-Myogenic mechanism
-Tubuloglomerular feedback mechanism

Creatinine Clearance

Creatinine clearance = GFR =% kidney function
Theoretically we all start with 100%

Proximal Tubule function

Primary function is bulk isosmotic reabsorption of glomerular ultrafiltrate.
Most of transport processes involve Na transport.
Countertransport involving H+ ions allows reclamation of most of filtered bicarbonate
-Phosphate is reabsorbed
-Glucose and amin

Loop of Henle Function

Thin descending and ascending limbs: passive water absorption and salt absorption
Thick ascending limb absorbs NaCl by an active, energy-dependent process. This segment is impermeable to water.
Hairpin arrangement and countercurrent flow maintain a papill

Distal Nephron function

Distal tubule is water impermeable segment that continues dilution of luminal fluid through active NaCl absorption.
Cortical collecting duct is sensitive to mineralocorticoid hormones.
Potassium secretion begins in distal tubule and continues along collec

Elimination Functions of the Kidney

Renal clearance
Regulation of sodium
Potassium elimination
pH-dependent elimination of Organic ions
Uric acid elimination
Urea elimination
Drug elimination

Antidiuretic Hormone (ADH)

Also called arginine vasopressin [AVP] or vasopressin
Synthesized in hypothalamus and stored in posterior pituitary
Antidiuretic effects of ADH results from its action on distal convoluted tubule and collecting ducts
ADH acts to increases cellular permeab

Physiologic stimuli for ADH

Changes in blood volume: Diminished volume (~ 10% loss) directly provokes ADH release
Changes in serum osmolality;
Hypothalamus is responsive to changes as small as 1% & ADH is usually secreted when osmolality exceeds 285 most
Dehydration results in ADH s

Reabsorption of Ca+
PTH acts on...
Where does Mg absorption occur?

Bulk of filtered Ca + is reabsorbed in proximal tubule (60%) with sodium.
Parathyroid Hormone (PTH) acts on cortical thick ascending limb and distal tubule.
Magnesium absorption occurs mainly in Loop of Henle.

EPO

Kidney major site of erythropoietin(EPO) production.
EPO is a highly glycosylated 39,000 dalton protein. It is produced in renal cortex.
It stimulates RBC production by its effects on BM
EPO production increases in states of decreased tissue oxygen delive

Renin

Juxtaglomerular cells produce and secrete renin.
Renin promotes production of angiotensin II, a potent vasoconstrictor that stimulates aldosterone production.
Aldosterone stimulates renal sodium reabsorption and excretion of potassium and hydrogen ions.
I

Vitamin D hydroxylation
Glucose homeostasis

Hydroxylation of Vitamin D to active form occurs in renal proximal tubular cells
Glucose Homeostasis: renal gluconeogenesis may contribute up to 40% of plasma glucose during prolonged starvation.

Renin angiotensin system

Renin cleaves angiotensinogen to produce Angiotensin I.
Angiotensin-converting enzyme (ACE) cleaves two amino acids from Angiotensin I (10 peptides) to produce the active octapeptide Angiotensin II.
Vascular endothelium especially the lungs contains ACE
A

Physiologic Effects of Angiotensin II

1. Constricts resistance vessels thereby increasing systemic vascular resistance & arterial pressure
2. Acts upon adrenal cortex to release aldosterone, which in turn acts upon kidneys to increase sodium and fluid retention
3. Stimulates release of vasopr

Blockade of Angiotensin

ACE inhibitors prevent AIAII conversion (ex. Captopril, enalapril)
AII receptor (AT1) blockers (Losartan, Valsartan) directly block AII vascular receptors

Vitamin D Metabolism

Vitamin D3 is produced in skin from steroid precursors.
Biologically active form, 1,25-dihydroxyvitamin D3 (calcitriol) is then produced in kidney by hydroxylation under control by calcium and phosphorus levels & PTH

Atrial Natriuretic Peptide (ANP)

28 amino acid peptide
Produced & stored by atrial myocytes
Release stimulated by atrial stretch
Produces vascular smooth muscle relaxation
Enhances NaCl & water excretion
Inhibits NaCl reabsorption
Opposes action of renin-angiotensin system

Kidney disease presentation

Variable
Nausea
Hematuria
Edema (Exclude CHF or hepatic cirrhosis)
Proteinuria
Electrolyte imbalance: Na, K, Mg, Ca, P
Uremia
HTN
Renal calculi
Infection (UTI)

Kidney disease epidemiology

Caucasian: majority, then AA

Kidney Disease Physical Examination

-Supine and sitting BP; neck veins (JVP)
-Check for rales on pulmonary exam
-Cardiac murmurs, friction rubs, S3
Abdomen: organomegaly or palpable masses; ascites; kidneys are not normally palpable on PE
-Check for peripheral pulses and edema
-Look for abn

Palpation of left kidney

Although lower pole is inferior to spleen, normal-sized left kidney cannot be palpated through abdominal wall.
When kidney enlarges, it can only push anteriorly and downward
Kidney lacks sharp edge of spleen

Palpation of right kidney

Since right kidney is lower, in some normal people lower pole may be palpable
Shapes of kidney and liver as dissimilar, so that an enlarged kidney feels different than an enlarged liver.
Kidney tumors may be smooth or irregular; when they enlarge they ext

Area of palpation of kidneys for tenderness (CVAT)

12th rib and transverse processes of upper lumbar vertebrae (costovertebral angle)

Initial laboratory work-up for RD

Obtain fresh urine sample for analysis
Obtain following in all patients suspected of renal insufficiency:
serum electrolytes, BUN, creatinine, calcium, phosphorus, uric acid , alkaline phosphatase, albumin , CBC, 24 Hour urine (for protein and creatinine

Urinalysis- color, specific gravity, pH

Color: normal urine clear & yellow.
-Dark brown or yellow suggests bilirubinuria;
-red: hemoglobinuria, myoglobinuria, porphyria, drugs such as rifampin and Pyridium
-turbid urine: pyuria, crystalluria
Specific Gravity: measures concentration of urine. Ra

UA - glucose, Hg, leukocyte estera, nitrite

Glucose: not normally found in urine (Renal threshold = 180 mg/dl)
Hemoglobin: Not normally found in urine. If present should lead to sediment exam
Leukocyte esterase: Positive dipstick indicates presence of at least 4 WBC/hpf on microscopic exam.
Nitrite

UA- ketones and protein

Ketones: Diabetic, alcoholic or starvation ketoacidosis.
Protein: Dipstick capable of detecting protein level 10-15 mg/dl. If positive, often followed by 24 hour collection.
-Unable to detect Bence Jones protein.
-False positive with Pyridium, urine ph >

Dipstick Protein Estimates

1+ = 30 mg/dL
2+ = 100 mg/dL
3+ = 300 mg/dL
4+ = 1,000 mg/dL

Proteinuria

Healthy adult excretes <150 mg protein per day in urine (Tamm-Horsfall mucoprotein)
-Glomerular filtration barrier restricts filtration
-Proximal tubule reabsorbs and degrades much of filtered protein
Abnormal urinary protein excretion >300 mg/day
Nephrot

Protein components in the urine

Filtered plasma proteins 80%
Tubular Tamm-Horsfall proteins 40%
Main plasma protein in urine is albumin
Normal albumin excretion < 20 mg/day
Dipstick urine detects mostly albumin

Spot urine protein/creatinine ratio

Using the ratio of urine protein to creatinine on spot random urine is accurate and eliminates need for a timed 24 hour urine collection.
Patients with normal excretion have a ratio less than 0.2. Patients with proteinuria have ratios between 0.2 and 3.5

Factors causing a increase in albuminuria

Blood in urine
CHF
exercise
excessive protein intake
fever
uncontrolled DM
uncontrolled HTN
UTI
Vginal fluid contamination
NSAIDs

Causes of decrease urine albumin

ACE inhibitors
Malnutrition
NSAIDs

Nephrotic syndrome labs

Urine protein > 3.5 grams
Hypoalbuminemaia -usually < 3.0
Hyperlipidemia -

Nephrotic Syndrome

1/3 of patients have a systemic disease
-DM
-SLE
-amyloidosis
Remainder have primary renal disease
-Adults: most common is membranous nephropathy
-Children: "minimal change disease"; "nil disease"; responds to corticosteroids in most cases; light microsco

Urinalysis: (Examination of urinary sediment- RBCs, WBCs, and renal tubular epithelial cells)

Supernatant is first decanted from centrifuged specimen. A drop is then transferred to a glass slide and a cover slip applied
RBC: up to 2 RBC/hpf may be found in normal urine
WBC: Up to 2 WBC/hpf may be seen in normal urine. Interstitial nephritis sugges

UA: Casts and Crystals

Casts: represent a mold of renal tubular lumen and are composed of protein and cellular elements
-Hyaline: mucoprotein matrix without cellular elements; benign; may be seen after strenuous exercise
-Red cell: indicates glomerular bleeding
-WBC (usually ne

If urine dipstick is positive for blood but NO RBC are seen on microscopic exam...

strongly consider possibility of myoglobinuria

Nephritic" vs "Nephrotic" Urine

Nephritic
-Active urine sediment, often with RBC casts
-Proteinuria, variable degree
-Patient often has azotemia, edema, hypertension
-Common causes: glomerulonephritis, vasculitis (SLE, Wegener's)
Nephrotic
-Benign urine sediment, with heavy proteinuria

Nephrotic Syndrome labs

> 3. 5 grams of protein in urine per 24 hours
Often accompanied by hypoalbuminemia (albumin < 3.5 g/dL), edema, hypercholesterolemia
Increased risk of atherosclerosis
Increased incidence of thromboembolic events including renal vein thrombosis

Hematuria
-symptomatic
-march hemoglobinuria

Symptomatic:
-Accompanied by excruciating pain(renal colic) suggests passage of a ureteral calculus or a clot from renal bleeding
-Hematuria with dysuria also can be associated with bladder infections or lithiasis.
March Hemoglobinuria:
-Seen in individua

hematuria labs

Increased numbers of RBC's with red cell casts, bleeding may be assumed to be renal in origin
If no casts or proteinuria, increased RBC's are suggestive of a bleeding site that is distal to kidney

Hematuria Evaluation

R/O Primary Renal Disease
-Check u/a for casts
-Check renal function
-Renal ultrasound / CT scan of kidneys R/O cancer, traumatic lesion
R/O Bladder Diseases
-Urine C/S to rule out hemorrhagic cystitis
-Cystoscopy to R/O bladder CA or polyps, -stones

Etiologies of Pyuria

-Acute or chronic localized inflammatory processes such as cystitis, prostatitis, & urethritis
-Pyelonephritis
-Calculi at any level resulting in stasis induced infection or inflammatory response
-Rupture of a renal or urinary tract abscess
Acute glomerul

Dysuria

-Pain on urination
-Frequently described as "burning"
-Due to inflammation of lower urinary tract
-May also imply difficulty in urination which may result from external meatal stenosis or from a urethral stricture
-Frequently associated with urinary frequ

Pneumaturia

Passage of air or gas in urine
Usually occurs at end of urination
Etiologies
-Introduction of air by instrumentation
-Fistula to the bowel
-UTI by gas-forming bacteria such as E.Coli or clostridia

Fecaluria

Presence of fecal material in urine & is rare
Results from either an intestinovesicular fistula or a urethrorectal fistula-ulceration from bowel to urinary tract
Etiologies:
-Diverticulitis
-Carcinoma
-Crohn's disease

Urinary Frequency

Defined as passing urine more often than normal
Nocturia is urinary frequency at night
Polyuria is increased amounts of urine
Etiology:
-Decreased bladder size-If an obstructed bladder cannot be completely emptied at each voiding, its effective capacity i

Urinary Incontinence- Overflow

-Inability to retain urine voluntarily
-Urge to urinate may be so intense that incontinence may result
-Occurs in pts who have chronically distended bladders(men with BPH)
-Pressure within bladder is constantly elevated
-Slight increase in intra-abdominal

Urinary Incontinence- Stress

-Leakage that occurs when patient strains
-Primary defect is loss of muscular support in urethrovesicular region
-Residual urine insignificant
-Any increase in intra-abdominal pressure causes leakage
-More common in woman

Measurement of Renal Function

Each kidney contains approximately 1 million filtering units (nephrons).
The principal measurement used to evaluate kidney function is glomerular filtration rate (GFR)
-GFR = SUM (Single Nephron Filtration Rates)
(This is called the "single nephron hypoth

Assessment of Glomerular Filtration

Blood Urea Nitrogen(BUN)
Serum Creatinine(Scr):
-primarily filtered at glomerulus with only a small but variable component of tubular secretion
-Increased Scr: ketoacidosis, ingestion of cooked meat, drugs that inhibit tubular secretion of creatinine (cim

Assessment of Renal Function: Clearance

Refers to the volume of plasma "cleared" completely of a marker substance by renal excretion per unit of time.
An ideal marker should be freely filtered into the urine after achieving stable plasma levels; it is then neither reabsorbed nor secreted in the

Clearance formula

Rate at which kidneys excrete solute into urine = rate at which solute disappears from blood plasma.
Cx = (Ux x V)/Px
Cx: clearance
Ux: concentration of x in urine
V: volume of urine formed in given time
Px: conc of x in systemic blood plasma

GFR formula

GFR also assessed using principles of clearance.
GFR = vol. of fluid filtered into Bowman's capsule per unit time.
GFR= (Ux x V)/Px

Solutes used to measure GFR

Required properties are:
-Solute is freely-filtered (conc. in Bowman's space = that in blood plasma).
-Tubules do not absorb, secrete or metabolize X.
Thus, amount of X in urine per unit time = that which glomerulus filters per unit time.
WHAT GOES IN = W

Drawbacks of Inulin

-Most reliable method of measuring GFR, not useful clinically.
-Inulin must be administered by IV to get relatively constant plasma levels.
-Chemical analysis of inulin in plasma and urine is technically demanding.
-Use Radiolabeled compounds instead like

Creatinine levels

Creatinine is secreted by tubules, so overestimate GFR by 20% in humans.
-However, colorimetry methods used to measure creatinine overestimate creatinine concentrations.
->Luckily, these 2 errors cancel each other out, and calculated creatinine clearance

Creatinine Clearance measurement

Useful in the diagnosis and prognosis of the kidney disease
Urine creatinine in mg/dl x Total volume of urine/Serum creatinine in mg/dl x 1440
Ref. Range: Male 125 ml/minute
Female: 115 ml/min
A decreased creatinine clearance is very sensitive indicator o

Relationship btw plasma creatinine and GFR

Negative logarithmic relationship- if creatinine goes from 1 to 2-> lose large amt of kidney clearence

Assessing GFR: BUN vs. Cr measurements

BUN: freely filtered at glomerulus, but because up to 50% is eventually reabsorbed, it does not provide a reliable estimate of GFR.
Increased BUN: high-protein diet, GI bleeding, tissue trauma, tetracyclines
Decreased BUN: low-protein diet, liver disease,

Serum Creatinine values

Normal Adults:
Male: 0.8-1.3 mg/dl (70-114 �mol/L)
Female: 0.6-1.0 mg/dl (53-88 �mol/L)
Children: increasing muscle mass
Male: 0.35 + (age in years)/40
Female: 0.35 + (age in years)/55

Total creatinine

Normal creatinine excretion rates: when patient is in metabolic equilibrium, the creatinine production rate does not vary from day to day so that the total creatinine can be used to assess the validity of a 24 h urine collection.
Males: 15-20 mg Cr/kg BW/

GFR with age

Normal GFR increases up to age 20, and progressively declines after age 40

BUN: Creatinine Ratio

Normal ratio 1:10 up to 1:20
Causes of high ratio:
-Shock, severe dehydration
-Congestive heart failure
-Upper GI bleeding
-Tissue trauma & catabolic state
-Corticosteroids
-High protein diet
-Tetracycline antibiotics
Causes of low ratio:
-Low protein die

Measuring the creatinine clearance:

Requires a 24 hour urine collection to measure the total amount (mg) of creatinine; volume recorded
Normal Values
-Males: 97-137 ml/min/1.83 m2
-Females: 88-128 ml/min/1.73m2
(precision may be enhanced with cimetidine 1200 mg before starting urine collect

Cockcroft-Gault formula:

GFR = (140-age in years) X (body wt Kg)/Scr x 72
Females: value for males X 0.85
Children:
GFR (ml/min) = [0.55 x ht (cm)]/Scr

Degree of decrease in GFR

GFR: 75-100% "decreased renal fxn"
(serum creatinine mostly normal or high normal)
GFR 25-50% "renal insufficiency"
(serum creatinine 1.5-3.0 mg/dL)
GFR 12-25% "chronic renal failure"
GFR <10% "Uremia", "end-stage renal failure

ESRD

The last stage of chronic renal failure; life cannot be supported without intervention by dialysis or transplantation

UREMIC SYNDROME

Results from retention of end products of protein metabolism with production of the clinical symptoms and signs of chronic renal failure.
There are multiple potential uremic toxins; administration of urea itself produces only mild symptoms.
Symptoms and s

Renal Imaging

KUB: plain film of abdomen: radiopaque stones may be seen
Renal Ultrasound
Intravenous Pyelography (IVP)
Retrograde Pyelography
CT scan of kidneys
MRI of kidneys
Radioisotopic renal scans
Renal Arteriography and Venography

Indications for Renal Ultrasound

To quantify renal size
To screen for hydronephrosis
To characterize renal mass lesions
To evaluate the perirenal space for abscess or hematoma
To screen for ADPKD
To localize the kidney for invasive procedures
To assess residual bladder volume > 100 ml
To

Renal MRI

As an adjunct to CT in evaluating renal masses
As an alternative to CT in patients who are intolerant of radiographic contrast agents
To evaluate suspected pheochromocytoma
To assess renal vein thrombosis

Renal Biopsy: US or CT-guided

Acute renal failure
-When the underlying cause of ARF is not evident initially, or recovery has not occurred following 3-4 weeks of supportive therapy.
Nephrotic Syndrome: glomerular disease
-Persistent Proteinuria of 2 g/24 h or more
Hematuria: microscop

The earliest sign of chronic kidney disease (CKD) is
A) microscopic hematuria
B) hypertension
C) proteinuria
D) abnormal creatinine
E) hyperkalemia

C) proteinuria

Assuming that a patient has maintained a normal baseline creatinine of 1.0 mg/dL with a normal glomerular filtration rate (GFR) of 100 mL/min, which of the following indicates a more significant change in the GFR?
A) increase in creatinine from 1.0 to 2.0

A) increase in creatinine from 1.0 to 2.0 mg/dL

Which of the following best describes the mechanism of action of angiotensin-converting enzyme (ACE) inhibitors in controlling blood pressure and preventing or slowing kidney damage?
A) they result in systemic vasodilation
B) they increase renal tubular e

E) they reduce production of angiotensinogen, the precursor to angiotensin I

Abnormal urinary protein excretion is defined as
A) > 30 mg/24 h
B) > 150 mg/24 h
C) > 300 mg/24 h
D) > 1 g/ 24h
E) > 3.5 g/24 h

B) > 150 mg/24 h

Which of the following diuretics is NOT potassium-sparing?
A) triamterene
B) amiloride
C) hydrochlorothiazide
D) spironolactone
E) eplerenone

C) hydrochlorothiazide