Lecture 4 The kidneys Flashcards
Functions of the kidney
- Excrete waste products
- Maintain the homeostasis of the ECF volume and its composition
- Hormone synthesis
Macroscopic overview of the kidney
- Blood enters through renal artery (~ 25% of cardiac output), leaves
via renal vein - Urine is collected in the renal pelvis and travels down the ureter to
the bladder - Functional unit is the nephron
Nephron (glomeruli)
Blood is filtered in the
glomeruli
ULTRAFILTRATE OF PLASMA:
* Similar to plasma in composition, but almost free of large proteins (i.e. albumin)
* The endothelium of the capillaries in the glomeruli acts as a barrier for RBC, WBC, and macromolecules
Nephron (proximal tubules)
Proximal tubules: bulk reabsorption
of the glomerular flitrate
Most ultrafiltrate is reabsorbed
Nephron (loops of Henle)
Loops of Henle: additional reabsorption through the countercurrent system
* Na and Cl is pumped out of the ascending Henle loop
* The increase in Na, increases osmolality in the surrounding area
* This causes water to diffuse out of the descending Henle loop
* Countercurrent: it goes against the direction of
the ultrafiltrate
Nephron (distal tubules)
Distal tubules: fine control of tubular
fluid
* The ultrafiltrate here is hypotonic
* Fine tuning of sodium reabsorption
(RAAS)→further diluting or
concentrating urine
* Excess of hydrogen ions are excreted
with ammonia (to buffer hydrogen
ions and maintain electrical
neutrality)
Disease processes affecting the kidneys can affect
fluid, electrolyte, acid-base homeostasis, and waste excretion!
How can we assess
kidney status?
We can assess glomerular filtration
ability (i.e. glomerular filtration rate,
GFR)
* We can assess glomerular integrity
* We can assess renal tubular function
The glomerular filtration rate (GFR)
The glomerular filtration rate (GFR) is the volume of fluid that passes
through the glomerulus per minute
* GFR is a marker of overall renal function
* Glomerular filtration rate is 120 ml/min
* In one day the kidneys filter 170 L → only 1-2 L of urine are produced
* GFR has a large reserve capacity (2/3 of GFR can be lost in chronic renal disease with minimal clinical symptoms)
Assessing GFR: clearance
We can estimate the GFR by measuring the urinary excretion of a substance when specific conditions are met (measured in ml/min)
* CLEARANCE: volume of blood completely cleared by a substance in a period of time
* We need to find a marker in our blood that can be completely filtered and cleared in one minute. This means it must not be secreted, reabsorbed or metabolized in the kidney
Assessing GFR: creatinine clearance
- Creatinine: metabolite of creatine, byproduct of muscle metabolism
- Daily production is relatively constant, cleared by glomerular filtration
- Creatinine clearance is the most widely used biochemical clearance test (simple and inexpensive)
- Creatinine clearance requires a urine creatinine concentration measurement as well as a plasma creatinine concentration (Urine creatinine x blood flow/plasma creatinine in 24 hours)
- Creatinine clearance in healthy adults is around 120 mL/min
Assessing GFR: plasma creatinine
Plasma creatinine concentration is the most reliable biochemical test to assess glomerular function [50-110 μmol/L]
* Note that ingesting a meal rich in meat/strenuous exercise can increase plasma creatinine levels, muscle mass also influences plasma creatinine
* Plasma creatinine concentration is inversely related to the GFR
* Plasma creatinine concentration within range might hide impaired GFR (we see an increase when the GFR decreases by 50%)→ patients at risk (i.e. diabetes, familiarity for kidney disease) are usually investigated further
Impaired glomerular integrity
when large molecules are not retained→ proteinuria
Impairment (glomerular integrity):
we see an increase of albumin in the urine
➢Albuminuria→ when detected with urine dipstick
➢Microalbuminuria→ when detected in laboratory analysis (not in dipstick)
Severe glomerular damage
we detect the presence of RBC in the urine (haematuria)
➢Macroscopic haematuria
➢Microscopic haematuria
Glucose (glycosuria)
most glucose is reabsorbed, so the presence can indicate renal dysfunction or diabetes mellitus
Low molecular weight proteins
i.e. β2-Microglobulin may indicate
renal tubular damage
Urinalysis
Routine analysis of urine consists of two parts
* Chemical analysis
* Microscopic examination of the sediment
* Good indicator of renal function
* A very effective screening tool for many common disorders
Urinalysis- physical examination
Color→ reflects the concentration of urine
* Clarity→ reflects the presence of bacteria or blood
* Specific gravity→ rough assessment of hydration of the patient and
concentrating ability of kidneys
Urinalysis- chemical analysis
- Proteins → assessment of renal tubular function
- Glucose → assessment of renal tubular function/diabetes
- Ketones→ may be present in diabetes/diabetic ketoacidosis
- Nitrites→ marker of UTI
- Leukocytes→ marker of UTI
- Haemoglobin → might suggest bleeding in the urinary tract
- Bilirubin → assessment of potential liver disease
Urinalysis- microscopic examination of the sediment
RBC, WBC???
Small numbers of RBC, WBC are a routine finding, if increased they
could indicate bleeding or infection
Urinalysis- microscopic examination of the sediment
Epithelial cells???
Epithelial cells are also a frequent find. Significant amounts might be
a sign of pathology
Urinalysis- microscopic examination of the sediment
Bacteria, yeast???
Bacteria, yeast: could indicate UTI or contamination of the sample
Urinalysis- microscopic examination of the sediment
casts???
Mucoprotein secreted into the collecting duct may precipitate out of solution and form into cylindrical “casts” of the tubule.
* Casts are cylindrical impressions of the nephrons Hyaline cast Cast incorporated with RBC and WBC Cast incorporated with WBC
Urinalysis- microscopic examination of the sediment
Calcium oxalate crystal???
dehydration, high levels increase
risk of kidney stones
Urinalysis- microscopic examination of the sediment
Triple phosphate crystal???
can indicate UTI
Acute Kidney Injury (AKI)
- Rapid loss of kidney function
- Urea, creatinine, hydrogen ions, other metabolic products are
retained - Oliguria (<400 ml urine/day) is typically present
- Potentially reversible (and can develop also in patients who already have CKD)
Types of AKI
Pre-renal : related to a decrease in renal blood flow
➢Dehyration
➢Hypotension
➢Haemorrage/severe burns
Intrinsic: damage to the kidneys
➢Diseases affecting the kidneys specifically (glomerulonephritis)
➢Systemic diseases that can interest the kidneys (systemic lupus erythematosus, SLE)
➢Drugs that induce kidney damage (i.e. some chemotherapics)
Post-renal: urinary tract obstruction
➢Kidney stones
➢Prostatic enlargement
➢Tumors
Pre-renal AKI
- Induced by a significant decrease in the GFR
- If adequate perfusion is not rapidly restored, pre-renal AKI may
progress to intrinsic kidney damage → We need to act ASAP!!! - It is the result of a normal physiological response to hypovolemia
(RAAS), but the problem is that we are also retaining waste products
Post-renal AKI
- Obstruction to the urine flow increases the hydrostatic pressure in
the collecting ducts - The increase in hydrostatic pressure can oppose glomerular filtration
- If this is prolonged, it can lead to renal tubular damage
Remove the obstruction asap to avoid permanent damage
AKI what can we find in our lab tests?
In the blood
➢Increased plasma urea
➢Increased plasma creatinine (not immediate, establishes through time)
In the urine
➢Decreased/increased sodium in the urine (depends on type of AKI)
➢Increased osmolality in the urine
➢Decreased bicarbonate
How to tell the two case studies apart
Step 1: is creatinine, urea, or both increased
* Step 2: is the capacity of concentrating the urine preserved→ How is
osmolality in the urine compared to the one of plasma?
➢If we can concentrate the urine, we would have a urine osmolality that is
increased and low or within range sodium levels (because we are able to
reabsorb it)
How to tell Pre-renal
- Pre-renal feature:
➢in the blood→ urea increase is more significant than creatinine
➢in the urine→ little sodium and high osmolality (osmolality in the urine much higher
than plasma osmolality)
How to tell Intrinsic renal feature
- Intrinsic renal feature:
➢In the blood → plasma urea and creatinine increase in a similar way
➢in the urine → very high sodium concentration, urine and plasma osmolality are
similar
How to tell Post-renal
- Post-renal: urine levels within range
➢There is no altered capacity of concentrating/diluting the urine, but an obstruction of
the urine flow. Urea and creatinine are increased in a similar way than pre-renal AKI
➢ To distinguish between the two, you look at the medical history/causes
Chronic kidney disease (CKD)
- Slow, progressive reduction of kidney function that leads to a decreased number of functioning nephrons (decreased kidney function for 3 or more
months) - Irreversible process
- Patients can be asymptomatic until the GFR gets closer to 15 mL/min (40% of people with severely reduced kidney function (not on dialysis) are
not aware of having CKD)
The natural history is the progression to kidney failure
Causes of CKD
- Diabetes mellitus (T1DM and T2DM)
- High blood pressure (hypertension)
- Cardiovascular diseases
- Family history of CKD
- Obesity
Clinical consequences of CKD
- Ability to concentrate urine is lost
➢Constant urine osmolality
➢Sensitivity to fluid loss/overload - Buffering function is reduced
➢Metabolic acidosis - Might have proteinuria (if nephron integrity is affected)
- Retention of waste products
- Decreased erythropoietin synthesis
➢anemia
Biochemical changes in CKD
Blood
➢Increased urea
➢Increased creatinine
➢Increased hydrogen ion concentration
➢Decreased bicarbonates
➢Decreased sodium
Others
➢Decreased GFR
➢Steady urine osmolality (can’t concentrate/dilute urine)
Management of CKD
Treat the underlying cause and attempt to slow down the progression
➢Strict control of sodium and fluid intake
➢Strict control of blood pressure and cardiovascular risk factors
➢Monitor and/or treat anemia
➢Manage endocrine disorders (diabetes)
➢Renal replacement therapy in KF (dialysis, kidney transplant)
Management of people with CKD is very complex!
