Week 8 Chronic Renal Disease Flashcards
Role of the Kidney
- Important role in the clearance of nitrogenous waste and other by-products of metabolism
- Responsible for regulation of fluid, electrolyte and acid-base balance
- Maintenance of urine production, blood pressure control, concentrations of ECF and ICF fluids, regulation of Ca-PO4 balance, vitamin D activation, hormone production and synthesis
- Filters 20% of the plasma and non-cell elements from the blood into the inside of the nephron (into the lumen)
- Reabsorbs the components that the body needs from the lumen back into the blood
- Secretes some unwanted components from the blood into the lumen of the nephron
- regulates pH
Describe the nephron
Functional unit of the kidney: Each kidney has approximately 1 million nephrons. Each nephron is composed of
* Glomerulus: fluid is filtered out of the blood (the ‘filtering unit’
* Tubules (Secretory/reabsorptive unit)
* Proximal tubules: where various substances are reabsorbed
* Distal Tubules & Loops of Henle: involved in the regulation of fluid and electrolyte levels
Electrolyte and fluid balance in the kidney
Role of ADH
Causes the kidneys to release less water, decreasing the amount of urine produced.
* stimulates water reabsorption in proximal and distal tubules
* critical for maintenance of fluid balance
* A high ADH level causes the body to produce less urine. A low level results in greater urine production.
Reabsorption from the Glomerular Filtrate
Notes:
* should have no glucose in the urine (exceptions: diabetes, infection, renal issues, too high TPN order)
* cann look at ostomy output to monitor electrolytes to see if wet or dry
What are the 3 main systems for acid-base balance regulation in the body?
- Buffer system
- Respiratory System
- Renal System
What is a normal pH in the body
7.35-7.45
* Values less than 7.35 indicative of acidosis
* Values greater than 7.45 indicative of alkalosis
* A variation above 0.4 can be fatal
How does pH effect protein?
- low pH proteins denature and are no longer functional
- high pH protein function and solubility affected
How does acid base balance typically work?
- pH decreases as H+ concentration increases/HCO1-3 decreases
- pH increases as H+ decreases /HC01-3 increases
Medical Problems with acid-base
Typically damage to one system (respiratory and/or kidney) and the other system tries to compensate
* Can cause imbalances
Describe the buffer system for acid-base balance
Fastest performer (works in seconds):
1. Bicarbonate ions combine with excess hydrogen ions to form carbonic acid
2. Carbonic acid is a weak, volatile acid; carbonic anhydrase converts this to carbon dioxide and water ; these are excreted quickly by the lungs and kidneys
- An increase in H+ causes a increase in carbonic acid, while a decrease in H+ causes a decrease in carbonic acid
- For every molecule of carbonic acid there are 20 molecules of bicarbonate: exchange in a 20:1 ratio to maintain acid base.
What must first be considered in acid base disorders?
pH in blood
* pH < 7.35=acidosis
* pH >7.45=alkalosis
What is pCO2? what happens with low versus high levels?
CO2 partial pressure is the ability of lungs to excrete C02.
* If the level is high then the lungs are having a problem with respiration.
* If the level is low then maybe the patient is hyperventilating or experiencing a response to an underlying metabolic disturbance in acid-base balance.
What are arterial blood gases critical for in determining?
- pH
- PC02
- HCO3
Buffer system equation
- pCO2 represents the acid part of the equation. Usually when this increases then pH in blood decreases.
- Bicarbonate represents the base part of the equation (as reflected in the CO2 levels in arterial blood).
- Need PCO2 +pH to calculate bicarbonate (or total carbon dioxide)
Difference between pCO2 and CO2 concentration
- pCO2 is partial pressures
- CO2 is actual concentration in blood
Describe the respiratory system for acid-base balance
Works in minutes
* The lungs eliminate excess carbon dioxide by increasing respiratory rate (low CO2); this causes a decrease in H+ and increase in pH. All of this occurs in increasing respiration. Conversely when respiration rate decreases (high CO2 occurs)
* Need to consider if a patient has an acid base issue whether or not the primary problem is a respiratory issue (e.g respiratory failure due to lung disease) or a respiratory response to an underlying metabolic problem (e.g as in renal failure).
Describe respiratory acidosis
Low pH and elevated pCO2 (put on ventilation)
* Typically caused by retention of CO2 (retention of CO2 can be caused by problems with ventilation ie. decreased respiratory rate due to damage in the lungs, or in CNS).
* More typical in acute lung failure or acute CNS damage.
* Note:its typically partial pressures of CO2 that increase - As pCO2, increase in the blood, H+ are retained within the blood. This results in decreased pH in the blood.
Primary problem of respiratory acidosis
lung failure and lower respiration
rates
Treatment for respiratory acidosis
improve ventilation to increase respiration and/or may need to initiate ventilatory support. This is needed to reduce pCO2
* In ARDS (decreased ventilation) the patient is often acidotic. So usually need ventilation support.
How can the renal system compensate for respiratory acidosis?
Kidney’s may also respond to this (hrs to days) by increasing excretion of H+ ions/increasing reabsorption of HCO3(1-)
* However, this may be insufficient to solve the problem without ventilatory support.
* Need a healthy kidney
* COPD often seeing kidneys chronically compensating
Cause of respiratory alkalosis
Increased respiration leading to excessive CO2 elimination (low pCO2 and elevated pH >7.45). This results in decreased pCO2, and hence decreased H+ ions leading to an increase in blood pH.
* This may occur when patient experiences lung damage and increases respiratory rates or possibly when surrounding O2 in the environment is decreased.
* In a ventilated patient this may occur when the patient is being weaned off ventilatory support and the O2 is decreased. The patients starts to breath more, but is unable to oxygenate sufficiently.
* Healthy person: athlete training in high altitide
Primary problem of respiratory alkalosis
lung disease/problems with excessive ventilation or rapid respiration
Treatment for respiratory alkalosis
Change partial pressure of CO2 (give more
CO2) that the patient breathes and/or change the partial pressures of delivered O2 (change ventilatory support) ie may increase O2 delivery.
* It really depends on what is the issue. You may do both.
* Will need to assess needs for a variety of medications to assist with supporting ventilatory status.
How does the renal system compensate for respiratory alkalosis?
For chronic conditions kidney’s may respond by reducing H+ excretion (or increasing
reabsorption in the proximal tubules) and up-regulating bicarbonate (HCO3(1-)) excretion
* need heatlhy kidneys
Describe the renal system for acid-base balance
Can take hours to days to work
* When blood pH increases (becomes more alkalotic) the kidneys respond by retaining hydrogen ions and excreting more bicarbonate ions
* When blood pH decreases (becomes more acidotic) the kidneys respond by excreting hydrogen ions and forming and retaining bicarbonate ions
Important consideration of the renal system with with acute respiratory function changes
Need to consider that the renal system is unlikely to be able to compensate for acute changes in respiratory function. Patients with acute respiratory dysfunction need ventilatory support and/or pharmacological support of respiratory function
What is metabolic acidosis
Increased production of acids (H+) due to a variety of disorders
* Underlying issue is renal or other organ dysfunction (eg Gl dysfunction)
Etiology of metabolic acidosis
- ↑ protein breakdown (consider ketoacidosis in Type 1 DM)
- diarrhea (due to Gl diseases particularly in large bowel where bicarbonate may be absorbed), lose a lot of biocarbonate in diarrhea
- medications
- renal insufficiency/disease (e.g renal tubular acidosis
this leads to excessive accumulation of H+ in body
Treatment for metabolic acidosis
- Main treatment: consider causes of organ failure and treat this. If patient has diarrhea (usually from lower bowel) due to Gl disease need to treat this (e.g short gut patients may need to be NPO; patients with IBD may need IBD treated).
- May need to give supplemental HCO3(1-) (typically in the form of sodium bicarbonate/potassium bicarbonate; but can also give citrate).
- Need to consider compensatory respiratory response (will be quite rapid) to lower pH which will be an increase in ventilation and/or the medical team which will want to improve ventilation to ensure excess C02 is removed to avoid respiratory acidosis. Goal will be for the team to IMPROVE/optimize respiration (Typically excess CO2 is associated with acidosis (but it can be normal as well; need to look at blood pH))
Describe metabolic alkalosis
Caused by excess elimination of H+ so pH is increased and pC02 typically remains normal/HCO31- is increased. (Total CO2 may be elevated; but not always). Focus on pH and HCO3 levels.
* usually diarrhea from upper bowel, prolonged vomiting, overdosing on antacids (Need to consider the “type’ of diarrhea..ie is this colostomy, jejunostomy, rectal discharge. This will influence the ‘type of ion lost’)
Treatment for metabolic alkalosis
Need to consider underlying cause…if due to prolonged diarrhea; need to treat underlying problem (antiemetic medication)
* May use other meds such as loop diuretics
* The idea is to reduce loss of CL1- ions.
Compensatory respiratory response to metabolic alkalosis
decreased rate of respiration so that the pCO2 can increase which will increase the level of H+ ions in blood
How does renal function affect blood pressure?
Kidneys influence BP by causing arteries and veins to constrict
1. In the distal tubule: very sensitive to changes in BP. This stimulates the release of renin (enzyme) when BP decreases
2. Renin activates Angiotensin-I to its active form Angiotensin-II and this results in vasoconstriction and increase in BP
3. Angiotensin-II stimulates adrenal gland to release aldosterone and this stimulates more sodium reabsorption in the distal tubule (water follows). This typically results in decreased urine output and increases circulating blood volume-get increased BP.
Sodium sensitive individuals
In high BP; there is a small percentage of people who respond to a lower sodium intake. Via aldosterone; these people are called ‘sodium sensitive individuals. Tends to be less than 50- 70% of the population.
* need to increase K+ intake too
Nutrient requirements for renal care
Need to know
Nutritional Recommendations about Potassium
Potassium binders are only recommended if have consistently high serum levels of potassium.
* Examples of these meds include: binding resins (eg Kayexalate, Lokelma or Veltassa).
* Large does of these meds can cause GI side effects like Nausea, vomiting, anorexia or constipation.
Treatment of hyperphosphatemia
phosphorous binders - should be taken at the beginning of a meal or snack and those with vitamin D are not commonly recommended. dosages may change frequently
* calcium carbonate (bonds phosphorous in foods)
* magnesium hydroxide (diarrhea side effect)
* sevelamer
Role of kidney in vitamin D formation
Kidney important in the hydroxylation of vitamin D (responsible for hydroxylation in the ‘1’ position).
What happens to vitamin D in renal disease?
get decreased hydroxylation of vitamin D; leading to bone related problems
* With decreased active vitamin D; the parathyroid increases synthesis and secretion of PTH (parathyroid hormone) because you have reduced calcium concentrations in blood (vitamin D stimulates calcium absorption in the gut).
* Also get increased excretion of calcium in the urine and then starts pulling from thr bone as becomes a high blood calcium
Evidence for Vitamin D Supplementation and Bone Health
- RCT examining 2000 IU/d vs 40,000 IU q month x 6 month. Significant increases in 25(OH) vitamin D levels.
- Daily dosing associated with high levels of markers of bone formation vs bone breakdown. No impact on quality of life.
- 25(OH) vitamin D levels > 100 nmol/L associated with increasing risk for sarcopenia.
- Longitudinal effects being studied over 3-5 years; stable bone health.
What is GFR?
Glomerular filtration rate → Measurement of kidney function via rough measure of the number of functioning nephrons
* ↓ in GFR = progression of disease OR development of a superimposed problem
* ↑ in GFR = improvement of renal function
How is GFR used in CKD?
Chronic Kidney Disease (CKD) is defined according to the presence of kidney damage and level of kidney function (glomerular filtration rate [GFR]), irrespective of diagnosis
* All individuals with GFR <60 mL/min/1.73 m2 for 3 months or more are classified as having CKD (common in elderly >65)
* Earlier stages of CKD can be detected through routine laboratory measurements
creatinine clearance to look at renal function
Normal range = 90-140 mL/min
* Needs a 24 hour urine collection
stages of kidney disease
Do not typically see symptoms until stage 5 (nausea, vomiting) and may not even be on dialysis yet
* stage 2 is normal GFR for elderly
Symptoms with renal failure
Initial symptoms may include the following (starting arounf 20ish GFR):
* Unintentional weight loss
* Nausea, vomiting
* Fatigue (often first), Headache
* Generalized itching
Later symptoms may include the following:
* ↑ or ↓ urinary output/urination at night
* Easy bruising or bleeding
* ↓ alertness
* Muscle twitching, cramps or seizures
* Uremic frost – deposits of white crystals in and on the skin
* ↓ sensation in the hands, feet, or other areas
Types of renal failure
- acute renal failure (ARF)
- chronic renal failure (CRF)
- uremic syndrome
- nephrotic syndrome
Common causes of ARF
not predisposed
* Sudden loss of blood (trauma, surgery, hypotension)
* Exposure to a nephrotoxin (e.g. angiography dyes)
* Streptococcal infection if severe
* Also: Cancer, prostate hyperplasia, renal calculi, strictures, clots, hemolytic anemia, blood transfusions, lupus, drugs (e.i. tylenol overdose)
What happens in ARF?
Rapid onset; may or may not be reversible
* Accumulation of waste (BUN and creatinine dramatically increase: BUN in excess of 20, creatinine; 700-2000 mmol/L)
* Hypoperfusion of the of kidney as in TX,
* Reduced urine output or in conditions where you may have inadequate fluid replacement during SX.
Phases of ARF
- oliguric phase
- anuric phase
- diuretic phase
- recovery phase
Describe the oliguric phase of ARF
Time span: 8-14 days
* urine output < 500 mls;
* get increased levels of urea, creatinine, K+, PO4, Mg, decreased levels of Na, CO2, Ca, hemoglobin
Describe the anuric phase of ARF
0-14 days
* urine output very low < 100 ml/24 hours
Describe the diuretic phase of ARF
time span : 10 days
* urine output 1.5-2x normal
* Risk of dehydration, electrolyte imbalances
* sign that kidneys have responded well to dialysis
What is important to consider in the oliguric and anuric phases of ARF?
- There is decreased production of erythropoietin (this is a factor made in kidneys that stimulates bone marrow to make RBC), getting Hb drop.
- Usually have to fluid restrict…otherwise get excessive fluid accumulation; restriction = urine output + 500-1000mL
Describe the recovery phase of ARF
4-6 months
* Can get in Tx
What are the ‘groups’ of CFR?
- Decreased renal reserve
- Mild renal insufficiency
- severe insufficiency to dialysis
Describe decreased renal reserve in CRF
- Irreversible loss of function of kidneys (months- years); slow progressive
- Get decrease in number of functioning nephrons
- Creatinine clearance: 50-80 ml/min (55% loss)
- BUN increases, nephron hypertrophy
Describe mild renal insufficiency in CRF
- Creatinine clearance: 25-50 ml/min (80% loss)
- Mild azotemia (N in blood)
- Fluid, protein and electrolyte disturbances may aggravate symptoms
- Have nocturia
- GFR ≤ 30 mL/min; stage 4-5
Describe severe insufficiency to dialysis for CRF
- Creatinine clearance < 10 ml/min (90-100% loss)
- Oliguric (100-400 ml urine output ; U/O)
- Anuric (100 ml u/o)
- May need tight fluid restrictions to prevent fluid overload
- Other symptoms: nausea, vomiting; ‘uremic syndrome’
Common causes of CRF
- hypertension and diabetes are the top 2!
- Diseases of the glomeruli (glomerulonephritis including: IgA nephropathy, MPGN, Goodpasture’s disease)
- Obstructive Diseases (obstructive uropathy, nephrolithiasis, hyperoxaluria)
- Lupus Nephritis and other systemic disease
- Drug abuse
- Hereditary Disease (e.g. polycystic kidney disease)
genetics influence severity and onset of kidney disease
Describe uremic syndrome
Urea build-up (usually associated with a urea >20)
* Affected by protein intake, renal function; may need dialysis
* Anorexia, vomiting, anemia, depression, hypertension, CJR, pruritus, hyperlipidemia
* Note: typically associated with patients that are in Stage 4-5 CKD
* Not all patients with CKD have Uremic Syndrome.
* poor QoL from dialysis and/or fractures from poor bone health
Describe nephrotic syndrome
Increased glomerular filtration of protein
* ? Etiology (viral, drug…)
* Get leakage of protein in urine…leading to hypoalbuminemia (albumin often lower than 30 g/L; normal 35-50); this results in decreased oncotic pressure in blood resulting in increased fluid accumulation in interstitial spaces… protein wasting, hyperlipidemia…
Secondary hyperparathyroidism occurs due to another disease (ESRD) that first causes low calcium levels in the body (want to control diet and use binders, vit D supplement).
* ↑ PO4: ↑ Ca from bones to maintain serum levels; soft tissue calcification
* ↓ calcitriol: ↓ Ca absorption in get; ↑ PTH works to balance low calcitriol
* ↑ PTH: Ca and PO4 imbalance; hyperparathyriodism (adenoma)
