Renal Disease Flashcards
where are the kidneys are situated
The kidneys are situated retro-peritoneally with the left kidney positioned slightly higher than the right.
Renal size
Renal size does relate to the size of the individual and therefore vary in length, but will generally range from length 11-14cm, width 5-6cm, depth 3-4cm.
Renal shrinkage is usually a characteristic of
Chronic Kidney Disease (CKD), with the kidneys being less than 8cm in length as a rule
The kidneys consist of the following cells and structures:
• Renal cortex • Renal medulla • Nephron - Renal corpuscle - glomerulus - glomerular (Bowman’s) capsule • Renal tubule -proximal convoluted tubule -loop of Henle -distal convoluted tubule • Collecting duct
Fundamentally kidneys act as a
The kidneys have a very complicated anatomy but fundamentally they act as a filter. They are very vascular organs receiving around 25% of the cardiac output which is one of the reasons why they are linked to cardiovascular disease e.g. hypertension, atherosclerosis
What is the nephron
The Nephron is the functional unit of the kidney and there are around 1 million nephrons in each kidney.
Excretion =
= filtration (Renal corpuscle) + secretion ( tubule) + reabsorption (tubule & collecting duct)
how much blood is filtered
Each day 170-180L of blood is filtered which approximates to a Glomerular Filtration Rate (GFR) of 120-130ml/min/1.73m2
- Reabsorption and concentration of urine also occurs to
produce a urine volume of 1 -2 litres/day.
Reabsorption is affected by
Reabsorption is affected by hormones, in particular
aldosterone and Anti-diuretic Hormone (ADH). Aldosterone is secreted by the adrenal cortex and acts on the distal tubule and collecting duct. ADH is secreted by the pituitary gland and acts on the collecting duct. Glucose, amino acids, sodium and water are reabsorbed in the proximal tubule and water is absorbed in the descending limb (which is impermeable to sodium). Sodium is absorbed in the ascending limb which is impermeable to water. This creates an interstitium hypertonicity (created by a countercurrent mechanism) which then leads to water being absorbed from the collecting duct. Urea is reabsorbed down a conc gradient which leads to concentrated urine.
Function of the Kidney
- Acts as a filter-regulation of fluid and electrolyte balance
- Removes waste products
- Removal of metabolic waste products
- Removal of foreign chemicals
- Balances body’s fluid content
- Regulates blood pressure
- Endocrine functions:
- Produces erythropoietin, essential for RBC production
- Produces Renin
- Activation of Vitamin D to 1,25dihydroxycholecalciferol to maintain healthy bones.
The kidneys balance
The kidneys balance the chemicals in the blood and produce hormones which control blood pressure and maintain healthy blood cells and bones, when kidneys fail these functions are impaired or cease. This reflects the medication you will see on a prescription for a patient with Chronic Kidney Disease (CKD).
renal failure can be described as
a decline in kidney function (glomerular filtration rate) resulting in an accumulation of waste products and other toxins. The GFR is kept fairly constant by regulatory mechanisms and the large extra capacity to function known as the “renal reserve”. An individual generally will have lost more than 50% of their kidney function before an increase in waste products e.g. urea and creatinine are observed.
A patient with renal failure can be
A patient with renal failure can be acutely unwell; this is usually in Acute Kidney Injury (AKI) or the onset may be more insidious; particularly in Chronic Kidney Disease (CKD). When kidneys fail to filter properly, waste accumulates in the blood and the body, and as the disease progresses, symptoms will become noticeable. Symptoms will vary from person to person.
Types of Renal Impairment
• Acute – Abrupt deterioration in renal function – Usually reversible • Chronic – Long-standing – Progressive • Acute on chronic – Abrupt deterioration on background of chronic renal impairment
Causes of Renal Impairment
• Pre‐renal – Decreased blood flow to the kidneys • Renal or intrinsic – Damage to or loss of nephrons • Post‐renal – Obstruction of filtrate along tubule / collecting duct / urinary system
All these cause a reduction in the GFR which leads to:
- Reduced ability to eliminate waste
- Reduced ability to regulate volume and composition of body fluid
- Increases in serum urea and/or creatinine
What is Chronic Kidney Disease?
At this stage of your studies you need to be aware that CKD is a chronic illness that can be caused by many factors which may include an existing co-morbidity e.g. Type 2 diabetes mellitus.
In general, it is non-reversible and can affect a range of body systems e.g. bone turnover, the cardiovascular system, haematological parameters.
what is acute kidney injury (AKI)
The term describes a rapid deterioration in renal function and is characterised by reduced urine output and increased serum creatinine. The cause of AKI can be pre-renal (eg, hypovolaemia), intrinsic (eg, acute interstitial nephritis) or post-renal (eg, urinary obstruction).
Diagnosing renal failure – investigations and laboratory tests
• Examination of urine
– Appearance, volume, chemical testing, microscopy
– Presence of blood, glucose, protein, micro-organisms
• Imaging – Abdominal X-ray, Ultrasound scan, CT, MRI
• Kidney Biopsy
• Blood tests
– Urea and creatinine
How is the GFR measured/estimated?
Serum creatinine – waste product of protein metabolism (mostly muscle)
Serum urea – nitrogenous waste products
Both urea and creatinine are crude measurements of renal function and should not be used alone as both urea and creatinine can be affected by many factors
Serum urea is affected by many factors: production
Increased by: • High protein diet • Increased catabolism • Surgery • Infection • Trauma • Corticosteroid therapy • Tetracyclines • Gastrointestinal bleeding • Cancer
Decreased by:
• Low-protein diet
• Reduced catabolism e.g. old age
• Liver failure
Serum creatinine
Can be affected by:
Non‐renal influences
• Gender and ethnicity: women have a lower serum creatinine than men. Individuals of African descent tend to have higher creatinine levels, people of Asian and Hispanic descent tend to have lower levels.
• Age: GFR declines with age. As a rule of thumb after the age of 40 an individual loses 10mL/minute per decade, so that at age 80, a normal GFR is 50-60 mL/minute.
• Body habitus: serum creatinine reflects body size, more specifically muscle mass. Obesity does not affect the serum creatinine or eGFR measurement but needs to be taken into account when using the Cockcroft and Gault formula.
• Muscle wasting, amputees: serum creatinine value is lower than expected given loss of muscle mass, and this must be taken into consideration when interpreting serum
creatinine and eGFR.
• Diet, hydration status, and medications: The GFR estimation calculations are not accurate in people on special diets (e.g. very high or low in protein). Altered hydration status will also affect serum creatinine, and thus the estimated GFR.
• Medications and medical conditions can alter creatinine levels or interfere with lab results: e.g. trimethoprim, amiloride, ascorbic acid; icterus
Drug handling in Renal Impairment - Absorption
Absorption - (not usually significant enough to justify altering doses)
• Nausea, vomiting and diarrhoea associated with uraemia, absorption becomes unpredictable
• may have GI oedema “soggy gut syndrome” e.g. in nephrotic syndrome in Congestive Cardiac Failure may need to change to IV diuretics
• Reduced GI motility and gastric emptying, especially if diabetic; can reduce time taken for the drug to be absorbed but does not generally affect the extent of
absorption.
• pH changes e.g. increased ammonia production in anaemia, patients with CKD may have the co administration of medications that increase the pH e.g.
phosphate binders, proton pump inhibitors, iron supplements
Drug handling in Renal Impairment - Distribution
Distribution
Changes to distribution may occur due to changes in fluid status
• Dehydration, oedema/ascites; salt and water overload or depletion affects
concentration of drug obtained
• Patients may be on diuretics, IV fluid, Renal Replacement Therapy (RRT) which will affect hydration status
• Important if small Vd (<50L) as Vd will be increased in uraemia, oedema or ascites and decreased in dehydration
• Lithium/aminoglycosides (also have a Narrow Therapeutic Index). When taking levels for TDM, the hydration status should be noted
• Reduced protein binding due to:
• Uraemia
• Malnourishment or protein loss (hypoalbuminaemia)
• Altered structural arrangement of albumin possibly reducing affinity or number of binding sites for drugs
• Important for highly protein-bound drugs (>80%); care with interpretation of TDM
• Reduced tissue binding
Drug handling in Renal Impairment - Volume of distribution (Vd)
- Considers lipid/water solubility and plasma/tissue binding of drug
- Drugs with low lipid solubility/high plasma binding tend to have low Vd
• Gentamicin - Drugs with high lipid solubility/high tissue binding have large Vd
• Digoxin
Drug handling in Renal Impairment - Metabolism
- Slower – higher adverse effects and toxicity where drugs are usually metabolised to inactive metabolites
- Consider if the drug’s metabolism is affected in uraemia? Some drugs can have a catabolic effect e.g. steroids
- Insulin 98% reabsorbed in tubules - 40% returned to venous blood, 60% metabolised. Metabolism is reduced therefore requirements in renal impairment are reduced
- Conversion of precursor to active metabolite reduced e.g. renal conversion of inactive cholecalciferol to active 1,25 dihydroxycholecalciferol
Drug handling in Renal Impairment - Elimination
- higher plasma levels of drugs renally cleared if drug is renally eliminated – this is the most important factor in whether to adjust doses or not
- metabolites of lipid soluble drugs may be water soluble and therefore toxic e.g. pethidine
