Mrs. Purva P.

Naik
DEPARTMENT OF BIOCHEMISTRY
TMH
Kidneys are the principal organs of the urinary system.

Primary functions are:

1.Regulate the volume and composition of extracellular fluid
(ECF)
2.Excrete waste products from the body‐ detoxify blood.
3.Increase calcium absorption ( activation of vitamin D ).
4.Stimulate RBC production by producing erythropoietin.
5.Regulate acid base balance.
6.Secretion of renin and angiotensin to regulate blood pressure
and
77.Electrolyte
y balance.
Outcome of multistep process of
Glomerular filtration,
Tubular reabsorption,
reabsorption
Tubular secretion,
&

excretion of
•water,
water
•electrolytes, &
•metabolic waste
products.
Urine is the result of the above process, but primary function is to
filter the blood and maintain the body
body’ss internal homeostasis.
homeostasis
Glomerular filtration:
•The amount of blood filtered by the
glomeruli in a given time is termed
the glomerular filtration rate (GFR).
•Normal GFR = 125 ml/min.

Tubular reabsorption:
•99
99% g
glomerular fitrate is reabsorbed
into the blood while it passes through
the renal tubules and ducts.

Tubular secretion:
•This removes excessive quantities of certain
dissolved substances from the body, and also
maintains the blood at a normal healthy pH ( pH 7.35 to pH 7.45).
Oli i diminished
Oliguria‐ di i i h d urine
i output related
l d to inadequate
i d
perfusion of kidney. UOP <400ml/day.
Uremia
Uremia‐ condition in which renal function declines and
symptoms develop. Accumulation of metabolic byproducts
(uric acid and creatinine) that are normally excreted by the
kidneys.
kidneys
Azotemia ‐ an excess of urea or other nitrogenous wastes in the
blood as a result of kidneyy insufficiencyy
Anuria‐ absence of urine formation.
Polyuria‐ large volumes of urine
Hematuria‐ blood in urine
Anemia‐ hemoglobin (Hb) <13 g/dL,
P i i itching
Pruritis‐ i hi or burning
b i skin.
ki
O
Occurs h kidneys
when kid l
are no longer bl tto clean
able l ttoxins
i and
d
waste from blood.
Symptoms of kidney failure: changes in urination, edema,
weakness, fatigue, ammonia breath, flank pain & itching.

Acute renal failure (ARF)

sudden onset
rapid reduction in urine output
U ll reversible
Usually ibl
Tubular cell death and regeneration
Chronic renal failure (CRF)
Progressive
Not reversible
Nephron loss
75% of function can be lost before it is noticeable
ARF
Pre‐renal = 55%
Pre‐
Renal (intrinsic)= 40%
Post‐‐renal = 5‐
Post 5‐15%
Causes of ARF
Causes Agents
g
PRERENAL
Hypovolemia Trauma, burns, surgery
Decreased effective plasma volume Nephrotic syndrome, sepsis, shock
Decreased cardiac output Congestive cardiac failure, pulmonary
embolism
Renovascular obstruction Atherosclerosis, stenoses
RENAL
Glomerular & small vessel disease Aggressive glomerulonephritis
Interstitial nephritis Infection, infilteration, drugs / toxins
Tubular lesions Post eschemic,
eschemic nephrotoxins,
nephrotoxins
hypercalcemia
POSTRENAL
Bladder outflow obstruction Prostatism, neurogenic bladder
Ureteric obstruction Stones, blood clots, tumors.
 Decrease urine output
p (70 %)
Edema, esp. lower extremity
Mental changes
N
Nausea, vomiting
iti
Pruritus
Anemia
Cool, pale, moist skin
Stages
Onset – 1‐3 days with increased blood urea nitrogen (BUN) and
creatinine and possible decreased urine output (UOP)

Oliguria
Oli i – UOP < 400 mL/day,
L/d elevated
l t d BUN,
BUN Creat,
C t Phos,
Ph K levels
l l andd
may last up to 14 days.

Diuretic (drugs) – UOP as much as 4000 mL/day but no waste

products, at end of this stage may begin to see improvement

Recoveryy – things
g go
g back to normal

or may remain insufficient and become chronic.

CRF
Progressive, irreversible damage to the nephrons and
glomeruli
Recurrent kidney infections,
infections vascular changes
(diabetes/hypertension) etc.

Regardless of the cause:

Decreased: gfr, tubular function & tubular reabsorption
capabilities
capabilities.
Dysfunction fluids & electrolytes, acid base disturbances.

Systemic problems develops end-stage renal disease

(esrd) occurs when gfr <15 ml/min
CRF Causes
 Diabetic Nephropathy
 Hypertension
 Glomerulonephritis
Gl l hii
 HIV nephropathy
 Reflux nephropathy in children
 Polycystic kidney disease
 Kidney infections & obstructions
Renal function tests
Tests Biological reference interval
BUN 6‐20 mg/dL
Creatinine Male: 0.7 – 1.3 mg/dL
Female : 0.6
0 6 – 1.1
1 1 mg/dL

Uric acid Male: 3.5 – 7.2 mg/dL

Female : 2.6 – 6.0 mg/dL

Potassium 3.5 – 5.1 mmol/L

24hrs. Creatinine clearance test Male 94‐140 ml/min
Female 72‐110 ml/min

Hyperkalemia may cause cardiac arrest

Dialysis
• A process for removing waste and excess water from the
blood,
• It is used primarily as an artificial replacement for lost
kidney function in people with renal failure.

 ½ of patients with CRF eventually require dialysis:

 Dialysis
 Diffuse harmful waste out of body
 Control
C l BP
 Keep safe level of chemicals in body
 2 types
yp
 Hemodialysis
 Peritoneal dialysis
Hemodialysis

 Machine
M hi filters
fil blood
bl d and
d returns it
i to body.
b d
 3‐4 times a week.
 Takes 2‐4
2 4 hours.
hours
 Peritoneal Dialysis
 Peritoneal dialysis works by using the lining of the abdomen
(peritoneum) as a filter.
filter
 It is used as an alternative to hemodialysis.
 There are three stages to a dialysis cycle
 FILL
 DWELL
 DRAIN
Case Study ‐ 1
 A 53 years old
ld patient
ti t complains
l i off frequent
f t thi
thirstt and
d urination,
i ti
lethargy, weakness, and blurred vision.
 A medical work‐up reveals the following:
• Blood
l d pressure: 164/93
/ mm Hg

• Fasting
g blood g
glucose: 210 mg/dL
g
• HbA1c: 9.4%

• BUN: 83 mg/dL
• Serum creatinine: 3.4 mg/dL

• Serum cholesterol:
h l l 230 mg/dL
d
• LDL: 163 mg/dL
• HDL : 25
5 mg/dL
g
 Lab findings
•Blood pressure: 164/93 mm Hg
Questions
Quest o s •Fasting blood glucose: 210 mg/dL
HbA1c: 9
•HbA1c: 4%
9.4%
•BUN: 83 mg/dL
•Serum creatinine: 3.4 mg/dL
g
•Serum cholesterol: 230 mg/dL
•LDL: 163 mg/dL
 Is this a renal failure case?
•HDL : 25 mg/dL
 Yes
 What is this condition known as?
 Diabetic nephropathy
 What
Wh t may be
b the
th cause??
 Uncontrolled diabetes leads to renal failure.
 What is the cause for high total cholesterol and LDL
cholesterol and Low HDL cholesterol?
 Uncontrolled diabetes.
Case study 2
 5 year old boy seen by a pediatrician for case of pneumonia,
he has had duringg the 3 month p period.
 Physical examination shows moderate to severe swelling of
ankles and face.
Lab findings are
 Spot urine protein 4+ by dipstick
 24
4 hr urine protein
p 8g g/24
4 hrs
 Serum albumin 1.4 g/dL
 Serum cholesterol 285 mg/dL
 BUN 11 mg/dL
/dL
 Serum creatinine 1.1 mg/dL
 CCT 633 mL/min
/
 Lab findings
Questions Spot urine protein
24 hr urine protein
4+
8 g/24 hrs
Serum albumin 1 4 g/dL
1.4
Serum cholesterol 285 mg/dL
 What is the diagnosis? BUN 11 mg/dL
Serum creatinine g
1.1 mg/dL
 Patient
P i has
h nephrotic
h i syndrome.
d CCT 63 mL/min
 What is the relationship between Pneumonia and renal
disease?
 Chronic protein loss through the kidneys has caused
hypo‐gammaglobulinemia resulting in decreased
i
immune response to infections.
i f i
 Does the child have azotemia?
 No neither BUN nor creatinine is elevated.
No, elevated
 How can CCT be decreased when serum urea and
creatinine conc. are within normal limits?
 CCT is considerably more sensitive to mild decreases in
renal function than BUN or creatinine concentration.
Case
5y
study
 75year
3
old Male with h/o p g
prostate cancer diagnosed in 2006.

 It was metastatic to his ribs at the time, so prostatectomy

was not done.
done

 He has done well since then on hormone therapy, but

presents to clinic today c/o abdominal pain and decreased
urine output over the last 5 days, as well as irritability and
back pain.

 His creatinine is 8.5 mg/dL

Q
Questions
 Is this renal failure?
Yes

 What type is it most likely to be?

Post renal from prostatic obstruction
Post‐renal,

 What tests clinician might order?

Bladder scan or post‐void residual; renal ultrasound

 How would clinician manage this?

 Giving fluids, following UOP and monitoring creatinine
level.
 1. The normal urinary system consists of:
A. two kidneys, two ureters, one urethra
B. two kidneys, one ureter, one bladder, one urethra
C. one kidney, two ureters, one bladder, one urethra
D. two kidneys, two ureters, one bladder, one urethra
9. Which of the following could potentially
cause renal failure:

A. Hypovolemic shock
B. Chemical exposure
p
C. Obstruction by kidney stone
D. All of these
BUN
 BUN is indicator of glomerular filtration rate.
 Liver breaks down proteins (regulated by rate of kidney
excretion) and produces ammonia — which contains
nitrogen.
 The nitrogen
g combines with other elements,, such as
carbon, hydrogen and oxygen, to form urea.
 Urea then circulates in the blood in the form of urea
nitrogen.
it IIn h
healthy
lth people,
l mostt urea nitrogen
it is
i filt
filtered
d
out by the kidneys and leaves the body through the urine.
Creatinine
It is a better indicator of kidney function.
It is a breakdown product of creatine.
 C
Creatinei is
i synthesized
h i d primarily
i il in
i the
h li
liver ffrom the
h
methylation of glycocyamine.
( synthesized from the arginine and glycine in the kidney).
 It is then transported through blood to the other organs,
muscle, and brain.
 where, through phosphorylation it becomes
phosphocreatine.
 During the reaction,
reaction creatine and phosphocreatine are
catalyzed by creatine kinase, and a spontaneously converted
to creatinine.
Uric acid
 Uric acid is the relatively water‐insoluble end product of
purine nucleotide metabolism.
 Three forms of kidney disease have been attributed to
excess uric acid: acute uric acid nephropathy, chronic urate
nephropathy,
ep opa y, aand duuricc acid
ac d nephrolithiasis.
ep o as s.
 2/3 rd uric acid is discharged from kidneys and 1/3 rd is
discharged from intestinal tract.
 Amount of uric acid produced and excreted each day is
almost same, hence if the production of uric acid is stable,
than the high uric acid is due to hindered excretion from
the kidneys and GI tract.
######
 Diabetes and hypertension are the leading cause of
ESRD
 Chronic
Ch i renall didisease is
i accompanied
i d by
b characteristic
h i i
abnormalities of lipid metabolism
 hypercholesterolemia accelerates the rate of
progression of kidney disease