Pathopharm 2: Exam 5 (Sleep and Sleep–Wake Disorders CNS Stimulants and Kidney)

Sleep is…

diminished consciousness where a person can be aroused by sensory or other stimuli

Sleep is when your body restores energy and repairs tissues

Decrease muscle activity, decreased GI digestion, and sympathetic NS is decreased

Non-REM

slow wave sleep. 80% of sleep is in this phase.  There are four stages;

NREM1 – slow rolling movements of the eyes, moderate activity, HR, BP, respirations slow down, cerebral activity decreases.  Onset of sleep first 1-7 minutes.

NREM2 – slow rolling movements of the eyes, moderate activity, HR, BP, respirations slow down, cerebral activity decreases.   Deeper than stage 1.  Lasts 10-25 minutes.  Requires more intense stimuli to arouse in this phase.

NREM ¾ - slow rolling movements of the eyes, moderate activity, HR, BP, respirations slow down, cerebral activity decreases.  Deep sleep.  Stage 3 is minutes.  Stage 4 is 20-40 minutes.  Increasing large stimuli needed to arouse

REM sleep

Clusters of rapid eye movements, motor movements suppressed with loss of muscle tone, hr, pr, resp rate increases, cerebral activity increases. 

Sleep vivid dreams and brain is highly active.  About 20% of sleep.  Brain can replay memories but not acquire new sensory information.

Required for normal daytime functioning.  Lack of _ sleep is associated with anxiety, irritability, inability to concentrate, if severe disturbed behavior, Is short in the first cycle 1-5 minutes but each subsequent cycle is longer

Dreaming in _ is bizarre and colorful.  Some can be short with fewer associations.

REM vs Non-REM sleep

Two distinct types of sleep that cycle roughly every 90-120 minutes.

Non-REM sleep- focusing on deep sleep, physical repair, and memory consolidation.

REM Sleep- characterized by high brain activity, vivid dreaming, and muscle paralysis (atonia).

Circadian rhythm

sleep wake cycle based on light/dark solar day.  Controlled in the hypothalamus – brain injury patients have trouble with balancing this

Melatonin

hormone from the pineal gland changes in circadian rhythm similar to those caused by light.  No light – melatonin produced.  Problems with daylight savings time and winter months.

Sleep disorders

inability to fall asleep, stay asleep, circadian rhythm and sleep-wake transition disorders, sleep –related breathing disorders (sleep apneas) and excessive sleepiness.

How to diagnose Sleep disorders?

made by history and exam.  Sleep diary and sleep log (2 weeks), sometimes sleep studies.

-Actigraphy

-Polysomnography

Actigraphy

measure of muscle motion.  Worn on ankle or wrist to measure body movement.  Indicator of wakefulness and sleep

Polysomnography

typical sleep study – uses eeg, emg, ekg, and pulse ox

Circadian Rhythm Sleep Disorders

occur when there is an incompatibility between circadian rhythms and sleep patterns.

Non-24-hour sleep wake rhythm disorder

free running disorder.  Lack of synchronizing between internal sleep wake rhythm and external 24 hour day.  Results in insomnia or excessive sleepiness.  Can occur in people that are blind or have brain lesions.

Treatment – bright light treatment or melatonin/melatonin agonists

Irregular sleep-wake rhythm

lack of consisten patter to sleep/wake cycle.  Total sleep time may be relatively normal but sleep periods are short throughout the day.  Common in people with neurodevelopment or neurodegenerative disorders.

Contributing factors – poor sleep hygiene, decrease environmental synchronizing factors, daytime activity and light exposure

Tx – bright light exposure.  Usually unresponsive to medications

Delayed Sleep – Wake Phase Disorder

Arise because of developmental changes in the sleep-wake cycle or because of poor sleep habits.

Main symptoms – extreme difficulty falling asleep at an appropriate time and difficulty waking up on time for work/school.  Most common in adolescents during puberty, mental illness.  Teens may be a social thing

Tx – good sleep hygiene and melatonin

Advanced  Sleep – Wake Phase Disorder

arise because of developmental changes in the sleep-wake cycle or because of poor sleep habits.

early sleep onset and early arising.  Trouble staying awake and waken early.  May be related to fast circadian rhythm

Tx-focuses largely on sleep schedule changes but is limited

Jet lag disorder

sleep changes when travel crosses several times zones.  Most people that cross 3-4 time zones can experience some sleep disturbances lasting for 2-4 nights

Manifestations – insomnia, daytime sleepiness, decreased alertness and performance, malaise GI symptoms

Tx – short acting hypnotics if short trip.  Long stays adapt to new time schedule quickly.  Get good sleep while on trips, small naps, good hydration and nutrition, avoid alcohol and caffeine before bed.

Shift work disorder

excess sleepiness and insomnia due to being awake during normal sleep time.  Sleeping on days off during normal schedule.  Adjusting sleeping patterns can be similar to jet lag

Sx-somnolence, napping at work, sleepinenss while commuting, insomnia on nights off.  Some sleep deprivation almost always.

Tx – try to sleep in absolute darkness may be beneficial to sleep

Insomnia

Very common, criteria difficulty initiating or maintaining sleep, adequate opportunity and circumstances for sleep, and daytime consequences such as fatigue, daytime sleepiness, irritability, and impaired attention or memory.

Risk factors – females, advancing age, ,anxiety

Treatment – sleep hygiene, cognitive behavioral therapt.  Medications reserved for short term therapy (4-5 weeks) benzos, Ambien, Lunesta, melatonin agonists, melatonin, antidepressants, and antihistamines (Benadryl).

Chronic Insomnia

often related to medical disorders (pain, immobility, hormonal changes, pregnancy, menopause) or psychiatric disorders (anxiety).  Other medical conditions like GERD, heart failure and respiratory disorders can occur at night as well.

Treatment – sleep hygiene, cognitive behavioral therapt.  Medications reserved for short term therapy (4-5 weeks) benzos, Ambien, Lunesta, melatonin agonists, melatonin, antidepressants, and antihistamines (Benadryl)

Short term Insomnia

less than (<) 3 months, usually caused by an identifiable emotional and physical stressor.  Factors like sleeping in an unfamiliar environment.

Treatment – sleep hygiene, cognitive behavioral therapt.  Medications reserved for short term therapy (4-5 weeks) benzos, Ambien, Lunesta, melatonin agonists, melatonin, antidepressants, and antihistamines (Benadryl)

Narcolepsy Pathophysiology

Recurrent attacks of drowsiness and sleep during daytime, Abnormal REM sleep regulation– peak incidence between 15-30 years old.  Abnormality in REM sleep regulation.

-No amount of nighttime sleep produces full alertness. Periods of daytime sleep are brief lasting 30 minutes or less often accompanied by interruptions of speech, lapses in memory and nonsensical activities.

Narcolepsy

Periods of daytime sleep are brief lasting 30 minutes or less often accompanied by interruptions of speech, lapses in memory and nonsensical activities.

Cause is unknonwn.  People usually have a high rate of human leukocyte antigen (HLA) – potentially autoimmune disorder

Hypocretins from hypothalamic cells cause wakefulness – deficiency in narcolepsy – potentially autoimmune. Neurologic insults that affect levels of hypocretin such as hypothalamic lesions, vascular, inflammatory or brain trauma

Dx – day and night time sleep studies

No cure – symptom management

Pharmacologic – stimulants amphetamines, tricyclic antidepressants, SSRIS.

Restless Leg Syndrome

5-10% of the US population

•Primary-genetic or family prevalence

•Secondary– iron deficiency, neurologic disorders, pregnancy, medications

Diagnosis- history of compelling urge to move legs usually associated with unpleasant sensations, motor restlessness.  Pacing, tossing and turning in bed, rubbing the legs.  Symptoms are worse at rest and get better with activity.

Treatment – Ropinrole (requip) Pramipexole (Mirapex), antiseizure medications, benzodiazapines, opioids

Obstructive Sleep Apnea

caused by upper airway obstruction.  Collapse of upper airway at pharynx level.  Airflow is stopped through nose and mouth for 10 seconds or longer.  People may have 300-500 apneic periods a night.

Risk factors – age, family history, obesity, alcohol or other drugs, hormone disorders, large necks

Manifestations-Snoring, Daytime sleepiness, Systemic Hypertension, Pulmonary Hypertension

Dx – sleep study test

Tx –weight loss, elimination alcohol and sedatives, proper positioning, CPAP, dental appliances, surgical treatment

Parasomnia

undesirable episodes that occur during sleep.

Night mares – vivid terrifying dreams abruptly awaken from sleep and difficulty returning to sleep.  10-50% of kids between 3-5.  Half of adults have occasional nightmares, 1% report nightmares at least once a week.  Most occur during REM sleep.  Can be a symptoms of PTSD after highly emotional experiences.

Sleep walking and sleep terrors occur between stages 3-4 of NREM. Sleep terrors sudden, loud terrified screaming and autonomic nervous system activation.

Walking – complex automatic behaviors aimless wandering rearranging furniture.  Dazed and relatively unresponsive.  Sleep deprivation and stress are common triggers.  Keep environment safe!

Bed wetting – neurological problems

Sleep Disorders

Difficulty sleeping in over 50% of adults 65 years and older and 40% of adults have chronic insomnia.  Usually results of medical or psychosocial comorbidities.

Frequent interruptions in sleep longer periods of wakefulness and shorter REM and ¾ NREM sleep

-Older adult sleep disturbance= Age-related changes, *Lack of exercise, *Poor sleep habits.

-Factors predisposing older adult to sleep disturbance= Physical and mental illness, Medication effects, Emotional stress.

CNS Stimulants drugs

are drugs that just like it sounds stimulate the CNS. Long term use of any of these medications can lead to psychological dependence or tolerance.  Larger and larger doses are needed

-Gradually starting and gradually stopping is important.  Abrupt stopping can lead to withdrawal symptoms.

Medically approved uses for CNS Stimulants

•Narcolepsy

•Attention-deficit/hyperactivity disorder (ADHD)

•Reversal of respiratory distress

Amphetamines

•Stimulates the cerebral cortex, CNS stimulants. Therapeutic use ADHD and narcolepsy. Prototype – Amphetamine Sulfate (Adderall)

Stimulates the release or neurotransmitters norepinephrine and dopamine from the brain and sympathetic nervous system and block reuptake of the neurotransmitters.

Causes euphoria and increased alertness.  Can cause restlessness, insomnia, tremors, irritability, weight loss, cardiac dysrhythmias.

Mechanism of action-Release norepinephrine and dopamine, Block reuptake

Pharmacologic effects

-CNS - Increased wakefulness/alertness, mood, reduce fatigue

-CVS – vasoconstriction, increase HR,

-High potential for abuse.

Methylphenidate (Ritalin)

Amphetamine-Like Drugs

Action= Modulates serotonergic pathways, Inhibits reuptake of NE and Dopamine.

Interactions

-Increase effects= Caffeine, anticoagulants, anticonvulsants, barbiturates

-Decrease effects=Decongestants, antihypertensives, insulin

Side Effects= sleeplessness, restlessness, nervousness, tremor, irritability, insomnia, loss of appetite.

Nursing Interventions= give before breakfast and lunch. Monitor child growth. Taper off

Analeptics

•Act on brainstem and medulla to stimulate respirations, restorative drugs or drugs that stimulate the CNS –primarily the respiratory center

CSN stimulants that affect the brainstem, spinal cord, and the cerebral cortex.  Primarily used to stimulate respiration

-Given to newborns to simulate respirations

CNS stimulant

•Caffeine-Stimulate respiration, promote wakefulness, half life of caffeine is 4 hours, however prolonged in liver disease.

Side effects-Restlessness, tremors, twitching, palpitations, insomnia

Anorexiants

•Act on satiety center in hypothalamic and limbic areas. can cause a stimulant effect on the hypothalamic and limbic regions of the brain.  Primarily used in weight loss to suppress appetite. Can be used for narcolepsy but not a first line treatment.

-Contraindicated in HTN and use caution with patients with diabetes, seizures, and bipolar disorder, CNS stimulants

Appetite suppressors

•Phentermine

Side effects-Restlessness, tremors, twitching, palpitations, insomnia

Attention Deficient Hyperactivity Disorder

Dysregulation of transmitters, Primarily in children before 7 and continues through teenage years.  Can be in early adulthood. Intelligence is not usually affected.

-Norepinephrine, dopamine, Serotonin,Deficient or ineffective neurotransmitter

•Characteristics- Inattentiveness, inability to concentrate, Restlessness, hyperactivity, impulsivity, Inability to complete tasks, poor coordination

Drug Therapy= CNS Stimulant

Depressants

Medications that decrease the functional activity within the CNS.  The degree of depression depends on the amount of the drug given and the amount.

•Primary use – Insomnia, Anxiety

Nonpharmacologic management should be attempted prior to using any OTC or prescription medication to promote sleep

Relaxation techniques – warm bath, quiet music, decrease exposure to loud noises, avoid a lot of liquor prior to bed

-Specific bed and wake time, Limit naps, Avoid caffeine – 6 hours before bed, Avoid heavy meals and exercise – 6 hours before bed

Sedatives

•Produce mildest form of CNS depression

CNS sedatives do not affect consciousness and are often used during the day time.

Sedatives were first prescribed to decrease tension and anxiety.

Benzos were for anxiety

Sedative-hypnotics

means natural sleep

Barbiturates

Benzodiazepines

Nonbenzodiazepines

OTC

•Sominex, Tylenol PM

•Diphenhydramine (Benadryl)

Barbiturates

Sedative-Hypnotics, Short term treatment to prevent dependence and tolerance.Three classifications;

-Short-acting (secobarbital sodium)→ useful in achieving sleep because they allow the patient to awaken early in the morning without experiencing lingering side effects.

-Intermediate-acting (butabarbital sodium)→ useful for sustaining sleep but may have residual drowsiness or hangover feeling in the morning.  This may not be ideal for patients that require daytime alertness.

-Long-acting (phenobarbital)→ useful for controlling seizures

MOA=Binds to and stimulates the GABA receptor

Therapeutic uses= Seizure, Induction of anesthesia, Insomnia,Anxiety

Adverse Effects= Respiratory depression, Suicide

Acute Toxicity

Can occur with Sedative-Hypnotics, Respiratory depression, coma, Pinpoint pupils

Treatment= Removal of barbiturate from the body, Maintenance of an adequate oxygen supply to the brain

Sedative-Hypnotics Types

Benzodiazepines as hypnotics, Drugs of choice to treat insomnia and anxiety, Seizures, Safer than other CNS depressants. Types;

•Alprazolam (Xanax)

•Temazepam (Restoril)

•Triazolam (Halcion)

•Estazolam

MOA – increase the action of inhibitory neurotransmitter GABA so neuroexcitability is decreased.

Adverse Effects-CNS depression, anterograde amnesia sleep driving, abuse. Benzos can affect stage 4 NREM sleep which may result in vivid dreams, nightmares, and delay REM sleep

Drug interactions-CNS depressants

Tolerance and physical dependence, Tolerance,Physical dependence

Nonbenzodiazepines (Benzo-like)

Sedative-Hypnotics, Neurotransmitters bind to gaba receptors so there is more gaba around.  Therefore there is less neuroexcitabilty

•Zolpidem (Ambien)-Short-term management of insomnia

Action- Neurotransmitter inhibition

•Eszopiclone (Lunesta)- Long term use

Sedative-Hypnotics Interactions and interventions

Drug interactions= Alcohol, CNS depressants

Nursing interventions= First use nonpharmacologic methods. Avoid alcohol, other CNS depressants. Monitor BP, RR. Withdraw gradually, Avoid in Elderly

Ramelteon (Rozerem)

Melotonin Agonists

•First FDA-approved hypnotic not classified as a controlled substance

•Selectively targets melatonin receptors

Adverse effects: drowsiness, dizziness, fatigue, headache, nausea, and suicidal ideation

MOA – selectively targets melatonin receptors to regulate circadian rhythm in treatment of insomnia

Anesthetics

General- Depress the CNS alleviate pain and cause loss of consciousness.

Local- Analgesia in limited area

Routes- Inhalation, IV, Topical, Local, Spinal

General Anesthesia

Balanced Anesthesia - may include; Hypnotic, Premedication- opioid analgesic, benzodiazepine, anticholinergic.A short-acting barbiturate

Intra-operative- Neuromuscular blocking agent, An inhaled gas or IV, A muscle relaxant

-Hypnotic given night before

-Premedication given 1 hour before surgery – anticholinergic – atropine to decrease secretions, Short acting barbiturate - propofol

Inhalation Anesthetics- Balance anesthesia, Desired mechanism of action, Minimum alveolar concentration

Side effects= Respiratory depression, Hypotension, Dysrhythmias, Hepatic dysfunction, Malignant hyperthermia

Types of intravenous Anesthetics

•etomidate (Amidate)

•ketamine hydrochloride (Ketalar)

•midazolam (Versed)

•propofol (Diprivan)

Used for general anesthesia or induction of anesthesia.  Short term drugs like propofol are given for outpatient procedures

Most of these medications have a rapid onset and short duration

Midazolam and propofol are given for induction and maintenance of anesthesia or for conscious sedation (colonoscopy) where you are in a twilight.  Patients are sedated and relaxed but responsive to commands.

Propofol (Diprivan)

General Anesthesia, Actions and uses- Unconsciousness develops within 60 seconds and lasts 3–5 minutes. Sedative-hypnotic for induction and maintenance of analgesia

•Mechanical ventilation and procedures

Adverse effects- profound respiratory depression, hypotension, bacterial infection. Bacterial infection because propofol supports microbial growth.  Discard unused amounts within 24 hours.

Amidate (Etomidate)

General Anesthesia, Potent hypnotic agent

•Induction

Ketamine hydrochloride (Ketalar)

General Anesthesia

Anesthetic effects

•Sedation, immobility, analgesia, and amnesia

Post anesthesia Medication

•Analgesics- pain magagment opioids, non-opioids, combination

•Antiemetics- nausea/vomiting (ondansetron/Zofran)

•Muscarinic agonist (cholinergic agonists) – Pilocarpine moistens the mouth

Local Anesthetics

•MOA - Suppress pain by blocking sodium channels, thereby blocking impulse conduction along axons.

-block pain at the site where drug is administer by preventing conduction of nerve impulses

•Topical Use: mucous membranes, broken or unbroken skin surfaces, burns. liquid sprays, ointments, creams, gels, powders.  Decrease sensitivity at the nerve endings in the affected areas.

•Local Anesthetics: dental procedures, suturing skin lacerations, minor surgery, blocking nerve impulses and diagnostic procedures

•Spinal Anesthetics

Local Anesthetic types

Procaine hydrochloride (Novocain)- synthetic cocaine

Lidocaine hydrochloride (Xylocaine)- replaced cocaine except in dental procedures

Bupivicine is a common medication used in pain pumps to give local pain relief to a site

Anesthetics

•Monitor patient’s level of consciousness.

•Monitor vital signs (respirations, HR, BP).

-Respiratory status

-Cardiovascular status

•Monitor urine output.

•Administer analgesics cautiously

The Neuromuscular Junction

•Point at which a motor neuron communicates with a skeletal muscle fiber to cause muscular contraction

•NMJ blocking drugs prevent nerve stimulation at the muscle cell

Used in conjunction with general anesthetic

Categories of Neuromuscular Junction (NMJ) Blocking Agents- Nondepolarizing

•Act as antagonists to acetylcholine (ACh) at the NMJ and prevent depolarization of muscle cells

Both types are used for paralysis  for surgical procedures, endoscopic procedures, or mechanical ventilation

Categories of Neuromuscular Junction (NMJ) Blocking Agents-Depolarizing

•One drug (Succinylcholine), the prevention of repolarizing results in muscle paralysis with the muscle in a constant contracted state

-Both types are used for paralysis  for surgical procedures, endoscopic procedures, or mechanical ventilation

•Acts as an ACh agonist at the NMJ, causing stimulation of the muscle cell and preventing it from repolarizing

Nondepolarizing NMJ Blockers Types

•Atracurium (generic)

•Cisatracurium (Nimbex)

•Pancuronium (generic)

•Rocuronium (generic)

Vecuronium (generic)

Nondepolarizing NMJ Blockers

Therapeutic actions and indications= Serve as an adjunct to general anesthetics during surgery when reflex muscle movement could interfere with procedure or delivery of anesthesia. Facilitate mechanical intubation by preventing resistance to passing of endotracheal tube or when patients “fight” or resist the ventilator

-Facilitate various endoscopic diagnostic procedures when reflex muscle reaction could interfere, Facilitate electroconvulsive therapy when intense skeletal muscle contractions as a result of electric shock could cause the patient broken bones or other injuries

-Similar in structure to Ach= Compete with ACh for the receptor site; occupy muscular cholinergic receptor site and do not allow stimulation to occur, Not broken down by acetylcholinesterase

Contraindications= Allergy Myasthenia gravis Renal or hepatic disease Pregnancy

Cautions= Personal or family history of malignant hyperthermia Pulmonary or CV dysfunction Altered fluid and electrolyte imbalance Some respiratory conditions Lactation\

Adverse effects= Associated with muscle paralysis Depressed respiration, bronchospasm, apnea. Histamine release à respiratory obstruction with wheezing and bronchospasm

-Hypotension, cardiac arrhythmias GI dysfunction Pressure ulcers Hyperkalemia

Nonpolarizing NMJ Blockers- Drug- Drug interactions or other

Drug–drug interactions- General anesthetics, Aminoglycoside antibiotics, Calcium channel blockers, Cholinesterase inhibitors, Xanthines, Alkaline solutions (e.g., barbiturates)

Drug–herb interactions- Valerian, melatonin, kava

Succinylcholine (Anectine, Quelicin)

Depolarizing NMJ Blocker,

Therapeutic actions and indications- Attaches to ACh receptor site on muscle cell, causing prolonged depolarization of the muscle. Causes stimulation and contraction, then flaccid paralysis

Adverse effects- Same as those for nondepolarizing NMJ blockers, Muscle pain, Malignant hyperthermia

Drug–drug interactions- Same as those for nondepolarizing NMJ blockers

Depolarizing NMJ Blocker Contraindications and Cautions

Contraindications- Some are the same as those for nondepolarizing, Boxed warning: pediatric patients, Malignant hyperthermia

Cautions- Fractures, Narrow-angle glaucoma or penetrating eye injuries, Paraplegia or spinal cord injuries,Genetic or disease-related conditions causing low plasma cholinesterase levels.

Primary function of the kidneys is to..

filter the blood and reabsorb molecules and secrete unneeded substances from the body.  Responsible for creating urine to be excreted from the body.

The products of metabolism are excreted in the urine – urea, uric acid and creatnine

Kidney regulate fluid balance and ion balance, Kidney has both excretory and endocrine functions

The endocrine include hormones that are secreted in the kindeys that allow for fluid balance

Structure of the Renal System

Nephron→ Kidneys are not able to regenerate nephrons so  once they are gone they are gone.  Losing nephrons is a part of aging.  After age 40 you lose 10% of nephrons each decade.

•Renal corpuscle

-Glomerulus, Bowman capsule

•Glomerular filtration membrane

•Juxtaglomerular apparatus

•Renal tubules: Proximal tubule, Loop of Henle, Distal tubule, Collecting duct.

Bowmans capsule

surrounds the glomerulus and functions to filter blood, Area of high pressure and ultra filtration

The Glomerular

filtration membrane is a small fibrous area that allows for small elements to pass into the glomerulus.

-each nephron has a glomerulus which filters blood and has a bunch of tubule structures that selectively reabsorb needed substances back into the blood and secrete unneded substance.

Juxtaglomerular apparatus

where renin is released which becomes important when it comes to the renin angiotensin aldosterone system

Proximal tubule

Active reabsorption of sodium

Loop of Henle

Concentration or dilution of urine.

-Descending loop of Henle is only permeable to water so lots of water is removed here.  This are is responsible for concentrating urine (remember concentration means that it has a lot of ions and other byproducts in it and very little water)

Ascending limb only allows ions to leave like sodium chloride potassium

Distal tubule

Reabsorb sodium and bicarbonate, Sodium and water are reabsorbed with the help of aldosterone and calcium under parathyroid hormone.  Bicarbonate is also reabsorbed. 

Hydrogen ions and potassium are secreted.

Items in the filtrate are:

Water, glucose, amino acids, urea, creatinine, ions (Na, K, Phos, etc).  BLOOD CELLS AND PROTEIN ARE NOT FILTERED THROUGH!

Renal cortex is most of the tubules

Proximal convoluted tubules and this is where most of the reabsorption takes place.  Here almost 100% of glucose, amino acids and water are reabsorbed. Other ions are also reabsorbed.  This is also where medication like antibiotics and diuretics are removed (so when we say medication are filtered in the kidneys, this is what we mean). 

Renal medulla

Loop of Henle.  The interstitial area here is very hypertonic or super salty.

End product is urine which consists of

urea, creatinine, water and ions (remember that these ions are what provides the urine concentration)

Renin-Angiotensin-Aldosterone System (RAAS)

This system manages our blood pressure when our blood pressure decreases. The goal of the RAAS is to activate angiotensin 2 which causes vasoconstriction which will increase blood pressure

When we have low blood pressure the Sympathetic nervous system stimulates the juxtaglomerular cells to release renin into the blood stream.

When renin in the bloodstream reaches the liver, the liver releases angiotensinogen which is an enzyme that makes angiotensin I. When angiotensin I is in circulation, the enzyme ACE or Angiotensin converting enzyme which is found on the surface of the endothelium in the lungs and the kidney. 

ACE then converts angiotensin 1 to angiotensin 2.  Angiotensin 2 is a very strong vasoconstrictor.  Blood vessels constrict which increases vascular resistance which increases blood pressure.

This system doesn’t stop here.  Body still knows that our blood pressure is low and vasoconstriction is just one way to increase the BP so now it focuses on retaining fluid so the kidneys start to save water and sodium.Adrenal cortex releases aldosterone which causes kidneys to hold onto sodium and water.

Pituitary gland causes antidiuretic hormone (vasopressin) release which causes the collecting duct to retain water

-This in combination with the vasoconstriction causes the blood pressure to increase.Again, when we get to cardiac medications, there are several that work in different areas in the RAAS

Test of Renal Function

•GFR

•Creatinine Clearance

•Plasma creatinine concentration

•Blood urea nitrogen (BUN)

•Urinalysis

GFR

creatinine clearance is traditional method of measuring GFR but now  estimated GFR is on metabolic panels.  EGFR uses a math formula to calcualate

Creatinine clearance

Creatinin is produced by muscles as the product of metabolism of creatine. Creatinine is filtered in the glomeruli but is not resabsorbed into the blood so the level varies depending on how well the glomerulus is working. You would not expect high levels or creatinine in the blood, therefore if kidney function is bad, creatinine goes up.  Creatinine should be filtered and excreted in urine

-Creatinine clearance is the rate for greatinine that is completely cleared by the kidneys in 1 minute

BUN

Urea is an end product of protein metabolism.  Blood levels are regulated by the kidneys.  BUN levels are related to GFR.  Again, urea is a waste product and should be excreted into the urine. Bun can be influenced by high protein intake, hydration status, bleeding.  In order for BUN to be elevated, about 2/3 of kidney function must be lost.

Urinalysis

specific gravity, concentration, infection markers become important when it comes to kidney function

Autosomal dominant- Cystic Disease of the Kidney

blisters on the outside of the kidney. Will have chronic conditions like HTN.  May need dialysis or renal transplants. 

Manifestations- Pain – renal colic, Hematuria, UTI, HTN

Autosomal recessive- Cystic Disease of the Kidney

cysts within the kidney itself where they are long elongated cysts in the collecting ducts.  Infants/newborns Supportive treatment many do not live past the first year of life. If children make it past year one morbidity and mortality are related to renal failure

•Manifestations= Pain – renal colic, Hematuria, UTI, HTN

Nephrophthisis

onset in childhood small shrunken kidneys and the presense of many cysts.  Usually begins with problems in the distal tubules.  These cysts eventually lead to CKD and failure.  Usually progresses to ESRD prior to adulthood.

Simple or acquired renal cysts usually benign often do not have symptoms.

Mainfestations in newborns – lack of urination or very dark concentrated urine,

Manifestations= Pain – renal colic, Hematuria, UTI, HTN

Obstruction Disorders- Upper

Kidney stones/renal calculi- Classified by mineral content

•Pathophysiology→Supersaturation – high mineral concentration→ Precipitation – salt from liquid to solid→ Growth – by crystallization→ Stone inhibitors.

-Supersaturated urine – when urine is supersaturated with stone components like calcium, urea, etc.Greater the concentration of two of these ions, the more likely they are to precipitate.

-Crystal aggregation – these small precipitates start to cluster together and for crystals.

-Stone inhibitors are things found in the urine that inhibit the stones from forming.  Citrate and Magnesium are natural stone inhibitors.  Increasing citate (potassium citate) may decrease the calcium stone formation in people that are likely to have that type of stone.

Types of kidney stones

Oxylate or phosphate (calcium) – high calcium, vitamin d intoxication, hyperparathroidis, use of antacids

Magnesium ammonium phosphate – urea splitting utis

Uric acid (urate) - gout

Cystine – high purine diet

Clinical manifestations of Kidney stones?

•Sudden pain

•Renal colic

•Hematuria

•Urgency, frequency

•Lower vs. Upper urinary tract infections

Lower uti – bladder and urethra

Upper ureters and kidneys

Bacteria – E coli #1 – klebsiella pneumonia, enterococcus faecalis, Enterobacter, pseudomonas aeruginosa

UTI associated with obstruction – urine sits and backs up.  Allows for bacterial breeding.  Increase in pressure in the area

Manifestations – pain with urination, frequency, lower abdominal pain, foul smelling cloudy urine.  If upper UTI may have more flank pain and systemic like symptoms (if infection reaches the kidney – blood constantly filters through kidney – so infection may go systemic)  – fever malaise body aches

Treatment – antibiotics – start broad and culture specific

Acute pyelenophritis

Infection of ureters, renal pelvis, may be cause because of significant urinary tract obstruction.

Caused by bacteria – typically gram negatives (Basically the same list from UTIs).  Usually ascends from the lower urinary tract.

Manifestation- Infection- abrupt signs of infection, Previous UTI

Chronic Pyelonephritis

Recurrent infection – damage, progressive scaring and deformation of renal calyces and pelvis from chronic infections

Manifestations- HTN, Kidney injury

Goodpasture’s Syndrome

Antiglomerular basement membrane disease, Affects 1-2% of the population.  Mostly young people 20-30s and older adults 60-70s. both pulmonary and renal symptoms (60-80%), the lower percentages will have either pulmonary or only renal symptoms.

Can include lung involvement (pulmonary-renal syndrome)

Etiology-Autoimmune, that attacks the collagen of the glomerulus and the alveoli of the lungs.  Leads to renal bleeding and pulmonary hemorrhage.

Pathophysiology- Antibodies develop against collagen within glomerular and alveolar membranes

Goodpasture’s Syndrome- Manifestations, diagnosis, and treatment

Manifestations- Flu-like symptoms, Hematuria, edema, HTN, Dyspnea, cough, pleuritic pain, hemoptysis

Diagnosis- Blood testing (antibodies, CBC, BMP), Urinalysis, Pulmonary function tests

Treatment- Plasmapheresis-removing antibodies attacking the body

-Immunosuppression

-In severe cases when there is severe destruction of the glomerulus can lead to Chronic renal failure – needing dialysis or renal transplant.  Lung symptoms may require lung transplant

Glomerulonephritis

common post infections especially strep infections.

Manifestation- Hematuria, Proteinuria, Decreased GFR, Oliguria, Hematuria with red blood cell casts, Proteinuria.

Other Glomerular Disorders

•Acute Nephritic Syndrome and Nephrotic Syndrome. massive proteinurea and lipiduria low albumin, generalized edema

Can be a primary disorder but is often a secondary disorder caused by diseases like diabetes and lupus

Pathogenesis- increased glomerular membrane permeability allows proteins to escape from plasma into glomerular filtrate.  Now there is low protein.  When low protein now there is excess water and sodium leading to edema.

-This could be a result of aldosterone stimulation as a compensatory mechanisim

Renal insufficiency

•25% normal function

End stage renal failure

•10% normal function

Acute Kidney Injury

Important for all types of renal failure is to treat and remove the underlying cause.

Pathophysiology

•Prerenal- Blood supply decreased. things that cause low blood pressure anaphylaxis, sepsis, hemorrhage, myocardial infarction, heart failure

•Intrarenal- Kidney tubule function decreased, Acute Tubular Necrosis. inside the kdineys and there is prolonged ischemia to the kidney.  An be caused by infection, hydronephrosis, medications – specifically antibiotics and NSAIDs

•Postrenal- Urine flow blocked, urinary obstruction

Acute Kidney Injury- Manifestations

Onset lasts hours or days.  From the onset of the precipitating event until tubular injury occurs

Oliguric lasts 8-14 days depending on nature of AKI.  Characterized by decreased gfr causing retention of urine and metabolites.  Urine is lowest at this point and there is severe edema.  U/O is less than 400/24 hrs.  BUN and creatinine are elevated

Diuretic phase is when you can tell recovery has started.  As GFR increases and returns to normal, increased urine output is the result.  Sodium and potassium levels decrease

Recovery – tubular edema and renal function improves.  This can last 3 -12 months

Chronic Kidney Disease

•Predisposing Factors= Diabetes, HTN, obesity, cardiac disease

Manifestations

•Creatinine clearance decreases

•Fluid and electrolyte balance

•Calcium, phosphate and bone

•Protein, carbohydrate and fat metabolism

Chronic Kidney Disease Manifestations

Sodium and water retention leads to hypertension and heart failure. Inability to excrete excess potassium leads to hyeprkalemia

Decreased elimination of wastes leads to increased uremia which leads to all of the symptoms on the bottom.  High levels of uremia leads to bleeding problems. Kidneys are unable to make erythropoietin which leads to decreased rbc production and anemaia

Imbalance in hydrogen ion secretion and excretion leads to acid base imbalances and acidosis. Vitamin D is inactivated so the body can not absorb calcium which leads to low calcium

Phosphate is retained so elimination is impaired – why patients need to take medications like phos lo when eating or other phosphate binders so phosphate is excreted in urine.

Calcium, phosphate, bone Reduced renal phosphate excretion, Phosphate and calcium inversely porportional

Hyperphosphatemia à hypocalcemia à increased PTH à calcium resorption from bone à bone loss, decreased renal synthesis vitamin D, and decreased serum calcium- pathologic fracture

Chronic Kidney Disease Alterations seen in following systems:

Cardiovascular – hypertension, heart disease (left ventricular hypertrophy and ischemic heart disease), pericarditis (often stage 5 because or uremia and prolonged dialysis)

Pulmonary – congestive heart failure symptoms

Hematologic – anemias and coagulopathies

Immune – infection common often related to dialysis and impaired inflammation

Neurologic – uremic encephalopathy – uremia causes CNS disturbances to delirum and confusion is common

GI – anorexia, N, V, ulcerations

Skin – pale r/t anemia or dusky. Dry skin and itchy

Chronic Kidney Disease Stages and S/S

I – normal kidney function, detect potential based on comorbidity

II – Mild (GFR 60 – 89 mL/min), still decent GFR but HTN develops. Hypertension

III – Moderate (GFR 30 – 59mL/min), first time see lab changes, HTN, BUN and Creatinine increase

IV – Severe (GFR 15 – 29mL/min, Anemia, metabolic acidosis, hyperkalemia, salt and water retention

V – End Stage (GFR less than 15), associated system disorders

CKD Treatment 

•Peritoneal Dialysis→ machine- remove fluid into abdomen, pulls what not needed, 10-12 hr each night.

•Hemodialysis- central line or fistula- blood removed, diaylesis pulls waste and give clean blood.

•Continuous Renal Replacement Therapy (CRRT)- ICU, seen in hemorrhage, constant, kidney not function at all, usually on kidney transplant list.

•Renal Transplant