Typical Causes of Hyperkalemia

•Increased release from cells:

•Hemolysis [leaking from mechanically damaged RBC]

•Metabolic acidosis

•Primary adrenal insufficiency

•Insulin deficiency

•Increased tissue catabolism

•Beta adrenergic blockade

•Exercise

•Reduced urinary excretion of K+

•Hypoaldosteronism (clinically important in the context of underlying renal disease)

•Renal failure

•Type 4 renal tubular acidosis

BUN/Cr

BUN/Cr Ratio

Urea handling by the kidney. The arrows indicate that urea is reabsorbed in the proximal tubule, secreted in the thin portions of the loop of Henle, and reabsorbed again in the inner medullary collecting ducts. The top halves of boxes indicate the percentage of the filtered load remaining in the tubule at a given location and the bottom halves indicate tubular concentration relative to plasma. Note that while the amount remaining in the collecting duct (and thus excreted) is half the amount filtered, the concentration is much higher than in plasma because most of the water has been reabsorbed. These numbers are highly variable, depending on several factors, particularly the hydration status.

BUN: Cr Ratio

The ratio of BUN to Cr can suggest hypovolemia because of differences in the way each is handled in the nephron. Both substances are passively filtered at the glomerulus, but whereas Cr remains within the tubule, the renal tubule is highly permeable to urea, which is passively reabsorbed with sodium. Therefore, in the setting of avid sodium retention, urea clearance is as low as 30% of GFR, whereas in the setting of adequate volume and sodium, urea clearance can increase to 70% to 100% of GFR. Thus, if the patient has normal concentrating ability, in the setting of prerenal failure, the serum ratio of BUN to Cr is typically >10. BUN level is depressed in patients with malnutrition and hepatic synthetic dysfunction and can be increased in the setting of protein loading, GI hemorrhage, or trauma. 

Decreased kidney function leads to an accumulation of urea and an inability to maintain electrolyte, water, and acid-base balance. The failure to adequately excrete urea, manifested as progressive elevation of blood urea nitrogen (BUN), serum creatinine, and other poorly defined toxins, results in uremia (see Chronic Kidney Disease below). Uremia is a syndrome characterized by a unique set of symptoms, physical examination findings, and laboratory abnormalities (see Table 16–7), presumably caused by a buildup of one or more uncharacterized toxins. In the absence of adequate renal clearance, ingestion of excess amounts of Na+, K+, water, or acids results in electrolyte, volume, and acid-base abnormalities that can be life threatening. Furthermore, excess Na+ ingestion in a patient with renal insufficiency results in intravascular volume expansion, which in turn can lead to hypertension and heart failure.

The clinical manifestations of acute kidney injury depend not only on the cause but also on the stage in the natural history of the disease at which the patient comes to medical attention. Patients with renal hypoperfusion (prerenal causes of acute kidney injury) first develop prerenal azotemia (elevated BUN without tubular necrosis), a direct physiologic consequence of a decreased GFR. With appropriate treatment, renal perfusion can typically be improved, prerenal azotemia can be readily reversed, and the development of acute tubular necrosis can be prevented. Without treatment, prerenal azotemia may progress to acute tubular necrosis. Recovery from acute tubular necrosis, if it occurs, will then follow a more protracted course, potentially requiring supportive dialysis before an adequate renal function is regained.

A variety of clinical tests can help determine whether a patient with signs of acute kidney injury is in the early phase of prerenal azotemia or has progressed to full-blown acute tubular necrosis. However, the overlap in clinical presentation along the continuum between pre-renal azotemia and acute tubular necrosis is such that the results of any one of these tests must be interpreted in the context of other findings and the clinical history.

Perhaps the earliest manifestation of prerenal azotemia is an elevated ratio of BUN to serum creatinine. Normally 10–15:1, this ratio may rise to 20–30:1 in prerenal azotemia, with a normal or near-normal serum creatinine. If the patient proceeds to acute tubular necrosis, this ratio may return to normal but with a progressively elevated serum creatinine.

Urinalysis is a simple and inexpensive test that serves as an important tool in the initial evaluation of the patient with acute kidney injury. The presence of hematuria and proteinuria should prompt an evaluation for GN. There are no typical abnormal findings in simple prerenal azotemia, whereas granular casts, tubular epithelial cells, and epithelial cell casts suggest acute tubular necrosis. Casts are formed when debris in the renal tubules (protein, red cells, or epithelial cells) takes on the cylindric, smooth-bordered shape of the tubule. Likewise, because hypovolemia is a stimulus to vasopressin release (see Chapter 19), the urine is maximally concentrated (up to 1200 mOsm/L) in prerenal azotemia. However, with progression to acute tubular necrosis, the ability to generate a concentrated urine is largely lost. Thus, a urine osmolality of less than 350 mOsm/L is a typical finding in acute tubular necrosis.

Finally, the fractional excretion of Na+

FENa+[%]=UrineNa+/PlasmaNa+UrineCr/PlasmaCr×100$FENa+[%]=UrineNa+/PlasmaNa+UrineCr/PlasmaCr×100$

is an important indicator in oliguric acute kidney injury to determine whether a patient has progressed from simple prerenal azotemia to frank acute tubular necrosis. In simple prerenal azotemia, more than 99% of filtered Na+ is reabsorbed, and the FENa+ will be less than 1% (except when the patient is on a diuretic). This value allows accurate identification of Na+ retention states (such as prerenal azotemia) even when there is water retention as a result of vasopressin release. With the progression of prerenal azotemia to acute kidney injury with acute tubular necrosis, this ability of the kidney to retain sodium avidly is generally lost.

Most damage in ATN is to proximal tubule (where 70% of Na is normally reabsorbed)

Mechanism of Oliguria in ATN – Tubuloglomerular Feedback

• 70% of ATN cases will cause oliguria (UOP < 500 ml/day).

• Glomeruli are actually intact in ATN. So why are they not filtering enough plasma to

generate urine?

• Total body water (TBW) accounts for about 50% of body weight. So an 80 kg person has 40 L of TBW. 1/3 of this 40 L is ECF, so that’s 13 L. 1/3 of ECF is intravascular fluid. So the plasma volume is 13 L x 1/3 = 4L.

• Healthy kidneys can filter 100 ml/min of plasma. That means it takes about 4000/100 = 40 min to filter all the plasma in the body. 

• 9% of the filtered plasma is reabsorbed by the tubules and returned to circulation. 

• In ATN, tubular reabsorption is impaired. If the glomeruli keep on filtering while the tubules are not reabsorbing, then a person can become volume depleted.

• So oliguria is really an adaptive response in ATN.  "Acute Renal Success"

Mechanism of Oliguria in ATN – Tubuloglomerular Feedback
• How does GFR get turned down in ATN?
• Answer: Tubuloglomerular feedback.
• ATN with tubular injury = reduced NaCl reabsorption at the PCT =increase NaCl delivery to macula densa at DCT = macula densa chemoreceptor activated and releases vasoactive compounds (adenosine)  = afferent arteriolar vasoconstriction and a fall in GFR = less filtration which in turn limits any further NaCl loss.

Renal Physiology Portion of RMR module

Renal Physiology Portion of RMR module

NBME Content Outline - Renal/Urinary System

NBME Content Outline - Renal/Urinary System.
(Step 1 item writers are assigned questions to write using this outline)

9.1 Normal processes
9.1.1 embryonic development, fetal maturation, and perinatal changes
9.1.2 organ structure and function
9.1.2.1 kidneys, ureters, bladder, urethra
9.1.2.2 glomerular filtration and hemodynamics
9.1.2.3 tubular reabsorption and secretion, including transport processes
and proteins
9.1.2.4 urinary concentration and dilution
9.1.2.5 renal mechanisms in acid-base balance
9.1.2.6 renal mechanisms in body fluid homeostasis
9.1.2.7 micturition
9.1.3 cell/tissue structure and function
9.1.3.1 renal metabolism and oxygen consumption
9.1.3.2 hormones produced by or acting on the kidney
9.1.4 repair, regeneration, and changes associated with stage of life

9.2 Abnormal processes
9.2.1 infectious, inflammatory, and immunologic disorders
9.2.1.1 infectious disorders
9.2.1.1.1 upper urinary tract
9.2.1.1.2 lower urinary tract
9.2.1.2 inflammatory and immunologic disorders
9.2.1.2.1 glomerular disorders
9.2.1.2.2 tubular interstitial disease
9.2.2 traumatic and mechanical disorders
9.2.3 neoplastic disorders
9.2.3.1 primary
9.2.3.1.1 renal
9.2.3.1.2 urinary bladder and collecting system
9.2.3.2 metastases
9.2.4 metabolic and regulatory disorders
9.2.4.1 renal failure, acute and chronic
9.2.4.2 tubular and collecting duct disorders
9.2.4.3 renal calculi
9.2.5 vascular disorders
9.2.6 systemic diseases affecting the renal system

9.3 Principles of therapeutics
9.3.1 mechanisms of action, use, and adverse effects of drugs for treatment of
disorders of the renal and urinary system
9.3.1.1 diuretics, antidiuretic drugs
9.3.1.2 drugs and fluids used to treat volume, electrolyte, and acid-base
disorders
9.3.1.3 drugs used to enhance renal perfusion
9.3.1.4 anti-inflammatory, antimicrobial, immunosuppressive, and
antineoplastic drugs
9.3.1.5 drugs used to treat lower urinary tract system
9.3.2 other therapeutic modalities

9.4 Gender, ethnic, and behavioral considerations affecting disease treatment and
prevention, including psychosocial, cultural, occupational, and environmental
9.4.1 emotional and behavioral factors
9.4.2 influence on person, family, and society
9.4.3 occupational and other environmental risk factors
9.4.4 gender and ethnic factors

taco paco peco paco

phyiological deadspace

Vd = tidal volume x (paco2 - peco2)/paco2

Vd = taco paco peco paco

Asthma Meds Side Effects and Asthma COPD Overlap

Asthma Meds

Side effects of beta-adrenoceptor agonists 

• Skeletal muscle tremor

• Cardiac tachycardia-tachyarrhythmias

• Modest prolongation of the QTc interval

• Tachyphylaxis

• Hypokalemia. 

• Nausea, vomiting, headache

Side effects of theophylline

• Positive chronotropic and inotropic effect. 

• Mild cortical arousal. 

• Stimulates secretion of gastric acid and digestive enzymes.

• Can cause hypokalemia, hyperglycemia, skeletal muscle tremors

• Can cause seizure- related to blood levels

• Can cause tachyarrhythmias

Side effects of glucocorticoids

• Linked to route and dosage

• Glucose intolerance, immunosuppression, bone demineralization, increase in weight, increased bp, decreased growth rate (children).

• Suppression of Adreno-pituitary axis (after 2 wks) with parenteral or oral. (use alternative day therapy)

• Throat thrush, oral hoarseness (inhaled preparations). can increase opportunistic infections

• Daily therapy for mild persistent asthma or short, intermittent courses of inhaled or oral corticosteroids 

Asthma COPD Overlap Syndrome (ACOS)

Figure 1. Hypothetical Course of Lung Function in Chronic Obstructive Pulmonary Disease (COPD) and Asthma.

COPD is an inflammatory disease of the small airways in particular and involves chronic bronchitis and tissue breakdown (emphysema). The disease may start with a low level of lung function as early as 25 years of age, followed by an accelerated decline in forced expiratory volume in 1 second (FEV₁) as compared with the normal decline. FEV₁ may decrease to 50% of the predicted (normal) value at 60 years of age and may go as low as 25% of the predicted value. During exacerbations, FEV₁ falls; the fall and recovery are more gradual than in asthma. In asthma, airway obstruction results predominantly from smooth-muscle spasm and hypersecretion of mucus. Exacerbations may accompany an accelerated decline in FEV₁ as well, with a rapid fall and more rapid recovery than in COPD. Progression of disease may occur in a subgroup of persons with asthma, leading to an FEV₁ of 50% of the predicted value at 60 years of age. FEV₁ seldom decreases to the low levels that occur more frequently in COPD. On the basis of an FEV₁ of 55% of the predicted value at 60 years of age, one cannot differentiate asthma from COPD. ACOS denotes asthma–COPD overlap syndrome.

Figure 1. Hypothetical Course of Lung Function in Chronic Obstructive Pulmonary Disease (COPD) and Asthma.

COPD is an inflammatory disease of the small airways in particular and involves chronic bronchitis and tissue breakdown (emphysema). The disease may start with a low level of lung function as early as 25 years of age, followed by an accelerated decline in forced expiratory volume in 1 second (FEV₁) as compared with the normal decline. FEV₁ may decrease to 50% of the predicted (normal) value at 60 years of age and may go as low as 25% of the predicted value. During exacerbations, FEV₁ falls; the fall and recovery are more gradual than in asthma. In asthma, airway obstruction results predominantly from smooth-muscle spasm and hypersecretion of mucus. Exacerbations may accompany an accelerated decline in FEV₁ as well, with a rapid fall and more rapid recovery than in COPD. Progression of disease may occur in a subgroup of persons with asthma, leading to an FEV₁ of 50% of the predicted value at 60 years of age. FEV₁ seldom decreases to the low levels that occur more frequently in COPD. On the basis of an FEV₁ of 55% of the predicted value at 60 years of age, one cannot differentiate asthma from COPD. ACOS denotes asthma–COPD overlap syndrome.

http://www.nejm.org/doi/full/10.1056/NEJMra1411863