Introduction to Renal

Disease
Dr. majula mumbaga
 Overview
• Review of Renal Physiology
• Signs and Symptoms of Renal Disease
• Investigations for Renal Disease
Examination of Kidney
Renal Anatomy
Renal Anatomy - Microscopic
Renal Physiology - Glomerular
Filtration
• The kidney filters 1L of blood / minute!
• Blood flows from renal artery  afferent
arteriole  GLOMERULUS  efferent
arteriole  renal vein
• The amount of serum that crosses the
glomerular basement membrane and
enters the nephron is the glomerular
filtration rate (GFR) and is normally
90-120 mL/minute
Renal Physiology - Glomerular
Filtration
• The GFR is determined by the pressure gradient cross
the glomerular basement membrane (glomerular
pressure)
• The body carefully autoregulates the GFR through 3
mechanisms:
1. Myogenic reflex of afferent arteriole to fluctuation in systemic
blood pressure
2. Tubuloglomerular feedback - increased tubular flow sensing
cells in the macula densa induce afferent arteriole constriction
3. Angiotensin II - when flow is reduced in the afferent arteriole
renin is released and causing vasoconstriction of the efferent
arteriole.
 Renal Physiology - Renal
Tubular Transport
• Once blood has been filtered through the
glomerular basement membrane it passes
into the tubules of the nephron
• The fluid is kept inside the tubules due to tight
junctions between the cells of the nephron
• Exchange of nutrients and electrolytes is
mediated by tranporters and the
concentration gradient along the nephron
The Nephron
 Renal Physiology - The
proximal tubule
• “The proximal tubule is responsible for
reabsorbing ~60% of filtered NaCl and water,
as well as ~90% of filtered bicarbonate and
most critical nutrients such as glucose and
amino acids”
– Resorption of bicarbonate is dependent on
carbonic anhydrases (ex. acetazolamide)
– Resorption of glucose is saturated at concentration
> 10-12umol/L
– Some rare diseases like Fanconi’s Anemia affect
the proximal tubule
 Renal Physiology - The Loop
of Henle
• Responsible 15-25% of Na/Cl
reabsorption (+ Mg and Ca)
• Important in creating concentration
gradient along nephron with increased
concentration within medulla
• Lasix, the most potent diuretic, acts
here by blocking the Na/K/2Cl
transporter
The Nephron
 Renal Physiology - Distal
Convoluted Tubule
• Responsible for 5% Na reabsorption (+
some Ca reaborption)
• This is the site of action of thiazide
diuretics which are generally weak
diuretics but potent antihypertensives
 Renal Physiology - Collecting
Duct
• Responsible for 5% Na reabsorption
• This is where concentration of urine
occurs
• Important for hormonal regulation of:
1. water balance (ADH)
2. Na+/K+ regulation (aldosterone)
3. acid-base status
• Site of action for K-sparing
diuretics(eg spironolactone,amiloride)
 Water Balance and ADH
• The serum osmolarity is tightly regulated at 280
mosmol/L
• If osmolarity , cells in the hypothalamus sense
this and stimulate release of ADH from the
posterior pituitary gland
• ADH acts on kidney to increase water
reabsorption
• ADH is effected in diseases like
SIADH(syndrome of inapropriate secretion of
antidiuretic hormone) and diabetes insipidus
 Sodium Balance and
Renin/Aldosterone
• Sodium balance determines blood volume
• If blood volume  this is sensed by baroreceptors of
arteries (ex afferent arterioles) and they release of Renin
• Angiotensin II acts directly on the proximal tubule to  Na
reabsorption and also stimulates secretion of Aldosterone
from the adrenal glands
• Aldosterone also acts on collecting ducts to  Na
reabsorption
• This system is called the Renin-Angiotensin-Aldosterone
(RAA) system
• Aldosterone is effected in diseases like Addison’s (adrenal
insufficiency) and Conn’s (hyperaldosteronism)
Signs and Symptoms of Renal
Disease
• Renal disease is difficult to diagnose at an
early stage because most of the signs and
symptoms of renal disease are nonspecific.
• The most common, early symptoms of renal
disease are fatigue, weight loss, itching,
confusion, abdominal pain, and fever
• Symptoms that are more specific for renal
disease include reduced urine output,
hematuria, edema and hypertension and are
usually occur later.
 Polyuria, Oliguria and Anuria
Definitions:
• Polyuria is > 3L of urine / day
• Oliguria is < 500mL of urine / day
– b/c 500mL of urine / day is the minimum
urine volume required to clear toxins
• Anuria is < 50mL of urine / day
Normal Urine Output (UOP) is
>0.5ml/kg/hour or >12ml/kg/day =
30ml/hr and 700ml/day in a 60kg adult
 Oliguria and Anuria
• Oliguria and anuria are generally a sign
of severe kidney disease (either acute or
chronic) and poor prognosis
• Most, early kidney diseases do not
cause oliguria or anuria
• It is possible to have significant renal
disease or injury with normal urine
output
 Causes of Polyuria
• Diabetes Mellitus
– Due to hyperglycemia
• Diabetes Insipidus (DI)
– Due to low ADH
• Primary or Psychogenic Polydipsia
– Due to drinking too much water
• Diuretic Use/Abuse
 S/S of Renal Disease - Edema
Edema can be a Symptom/Sign (S/S) of many
different conditions.
Edema is generally occurs via 5 mechanisms:
1.  sodium retention (ex Chronic Kidney Disease)
2.  hydrostatic pressure (ex Congestive Cardiac Failure)
- usually causes dependent edema but can be
generalized if severe
3.  oncotic pressure (ex nephrotic syndrome or cirrhosis)
- usually causes generalized edema including face
4. Leaky capillaries (ex medications like calcium channel
blockers)
5. Lymphatic or venous (ex filiariasis, Kaposi’s Sarcoma)
S/S of Renal Disease - Edema
Examination for edema requires determining
extent and nature of edema
Edema is not detectable until 4-5kg of extra
fluid are present
Most edema is pitting but some conditions
cause non-pitting edema (ex Kaposi’s
Sarcoma, filariasis, hypothyroidism)
Severe, generalized edema is called
anasarca.
 S/S of Renal Disease - Edema
Several different renal diseases can cause
edema:
1. Acute Kidney Injury / Chronic Kidney
Disease - Na retention due to GFR
2. Glomerulonephritis (Nephritic Syndrome)
- GFR
3. Nephrotic Syndrome - albumin 
oncotic pressure and  blood volume 
 renin/aldosterone +  Na reabsorption
(generalized edema)
S/S of Renal Disease - Edema
Other causes of edema include:
1. Congestive Cardiac Failure ( hydrostatic
pressure +  aldosterone)*
2. Cirrhosis ( oncotic pressure + 
aldosterone)*
3. Malnutrition ( oncotic pressure)
4. Hypothyroidism
5. Drugs (ex CCB) - various mechanisms
 S/S of Renal Disease - Red
Urine
• If patient has red urine - check dipstick
• If urine is red and/or urine dipstick shows
+ heme this could mean:
1. RBC’s in urine (true hematuria)
2. Hemoglobin in the urine (hemolysis)
3. Myoglobin in the urine (rhabdomyolysis)
• Dipstick with + heme should be confirmed
with centrifuge and urine microscopy to
see if RBCs are present
 Causes of True Hematuria
True Hematuria = RBCs in the urine
• Renal
– Glomerulonephritis*
– Polycystic kidney disease
– Papillary necrosis (SCD)
– Trauma
– TB
• Ureters - stones*
• Bladder
– Schistosomiasis*
– Neoplasm*
 S/S of Renal Disease - HTN
• Many form of renal disease, especially
those affecting the glomeruli, are
associated with HTN
• Pt with HTN develop renal failure
• The prognosis of many renal disease is
dependent of level and control of BP
 S/S of Renal Disease - other
• Other important S/S of renal disease
include:
– Renal angle tenderness (ex pyelonephritis)
– Generalized pruritus (uremia)
– Uremic frost / uremic pericardial rub
– Enlargement of kidneys (ex Polycystic
Kidney Disease)
– Renal Bruits (renal artery stenosis)
 Renal Investigations - Urine
Sample
• Sample should be mid-stream urine (MSU)
• Describe appearance
– Deep yellow = dehydration or bilirubin
– Turbid = phosphate crystals or WBCs
– ‘Smoky’ urine = few RBCs (ex nephritis)
– Red urine = hematuria, myoglobinuria,
hemoglobinuria or meds (ex Rifampin)
– Frothy urine = protein (ex nephrotic)
– Milky urine = chyluria (ex filariasis)
Renal Investigations - Dipstick
Must be timed and read carefully!
– pH - nL is 4.5-7.5 depending on diet;  with
Proteus; also important with crystals
– Specific Gravity (SG) - nL is 1.005-1.030
depending on hydration; useful in polyuria
as SG  (<1.005) in DI but  (>1.020) in
DM
Renal Investigations - Dipstick
• Protein
• Heme
• Leukocyte Esterase (WBC)
• Nitrites (Gram negative bacteria)
• Ketones (+ in DKA and fasting)
Renal Investigation - Microscopy
of Centrifuged Sample
• RBC: <2cells/HPF is normal; >2 seen with
contaminated sample, UTI, stones,
malignancy, PCKD; in GN the RBCs are
dysmorphic
• WBC: <4cells/HPF is normal; usually PMNs;
>4 is hallmark of UTI (including TB)
• Epithelial Cells: generally nonpathologic
• Malignant Cells
Renal Investigation - Microscopy
of Centrifuged Sample
Casts = cellular debris + glycoproteins
deposited in the tubule
– Hyaline casts - protein; fever and exercise
– RBC casts - diagnostic of
glomerulonephritis
– WBC casts - usually pylenophritis
– Epithelial casts - ATN (‘muddy brown’)
– Granular casts - from degeneration of other
casts; pathologic but nonspecific
Renal Investigation - Microscopy
of Centrifuged Sample
Other findings include:
– Crystals
– Bacteria (UTI)
– Ova of Shistosoma hemotobium
 Renal Investigations -
Creatinine
• The most accurate, simple measure of renal
function and glomerular filtration
• The GFR can be estimated from the creatine
using the Cockroft-Gault equation:
Males: 1.23 x ((140-age) x weight (kg))/creatinine
Females: 1.04 x ((140-age) x weight (kg))/creatinine
– (Cr in mmol/L)
• Since creatinine comes from muscle the level
will by higher with  muscle mass and lower
with  muscle mass
 Renal Investigation - Urea
• A less accurate measure of renal
function.
• Dehydration, increased protein
consumption, GI bleeding and steroids
can also elevated the Urea.
• Useful in determining if patients
symptoms are due to uremia.
 Renal Investigations -
Ultrasound
Useful for:
1. Evaluating renal anatomy - cysts,
tumors, stones easily seen
2. Evaluating echogenicity - if  indicates
fibrosis and usually CRF
3. Evaluating bladder - bladder neck
obstruction, stones, tumors and ability
to empty bladder
 Renal Investigations -
Abdominal XRay
• Kidneys are usually not visible by XRay
• Useful in detecting kidney stones that
are made of calcium
• Also can be used to see calcified
bladder as seen in urinary
schistosomiasis
Renal Investigations – Intravenous
Pyelourogram (IVPU)
• Involves injecting contrast in the veigns and
then taking Xrays at 5, 10, 20 minute intervals
and then pre/post micturation
• It is useful for outlining the GU outflow path
and can be used to detect problems with:
– Calyces, pelvis, ureters and bladder
• Should not be used in patients with renal
failure as intravenous contrast is nephrotoxic
 Renal Investigations - Biopsy
Carries significant risk of bleeding so
reserved for:
– Nephrotic syndrome
– Nephritic syndrome
– Unexplained Chronic Renal Failure
 Summary
• Renal Anatomy and Physiology
• Symptoms/Signs of Renal Disease
• Investigations of Renal Disease
 Sources
• Harrisons Textbook of Medicine
• Oxford Handbook of Tropical Medicine,
3rd edition
• Principles of Medicine in Africa