Exam 4 Flashcards
Guillain-Barre´ Syndrome
Prototype: Acute Inflammatory demylinating polyradiculoneuropathy (ADIP)
Post infectious polyneuropathy
Ascending symmetrical paralysis (over 12 days- 4weeks)
Acute , rapidly progressing and potentially fatal form
Guillain-Barre´ Syndrome incidence
more in males, 1.8 per 100,000
Guillain-Barre´ Syndrome etiology
Unknown cause but involves cellular and humoral immune system. Development of IgG antibodies
Thought to be an autoimmune response to antibodies formed in response to a recent pathological event.
Guillain-Barre´ Syndrome patho
T cells migrate to the peripheral nerves resulting in edema and inflammation, macrophages invade the area and break down the myelin
More inflammation around the demyelinated areas cause further dysfunction
Once the temporary inflammatory response halts the myelin regenerates.
If there is damage to the axon itself, residual neurologic dysfunction may occur.
Myelin in Guillain-Barre´ Syndrome
- Loss of myelin, edema and inflammation of nerves
- Immune system overreacts to the infection and destroys the myelin sheath
- As myelin is lost
- Nerve impulse transmission slows down or is totally lost
- Muscles denervate and atrophy
- In recovery nerves re-myelinate
- Nerve function returns slowly in a proximal to distal pattern.
Triggering events for Guillain-Barre´ Syndrome
- Campylobacter jejuni gastroenteritis= 30% of cases.
- viral infection 1-3 weeks prior to onset (usually involving the upper resp tract)
- Bacterial infections
- Vaccines
- Lymphoma
- Surgery and Trauma
Clinical Manifestations of Guillain-Barre´ Syndrome
Weakness of lower extremities (hours to days to weeks), Paresthesia, Paralysis
Hypotonia – reduced muscle tone, Areflexia
ANS dysfunction: orthostatic hypotension, hypertension, abnormal vagal response (heart block, bradycardia), bowel and bladder dysfunction, flushing, diaphoresis, SIADH,
Cranial Nerve involvement: facial weakness, EOM difficulties, dysphasia and paresthesia of the face
Respiratory Failure – may require intubation and ventilation
Pain- no sensory neurons are effected
CSF may reveal elevated protein level
Diagnostic studies for GB
History and Physical Initial CSF normal with low protein. After 7-10 days protein increases Electromyography (EMG) and nerve conduction test show reduced nerve conduction Brain MRI done to rule out MS
Treatments for GB
Plasmapheresis- the removal of plasma and components that may be contributing to disease states. (removal of antigen and antibody complexes)
Administration of immunoglobulin (Sandoglobin)
Rehabilitation
Factors that influence ICP
Arterial and venous pressure Intraabdominal and intrathoracic pressure Posture Temperature Blood gases (CO2 levels)
Monro-Kellie doctrine
If one component increases, another must decrease to maintain ICP.
Normal ICP
5 to 15 mm Hg
Elevated if >20 mm Hg sustained
To decrease brain volume
remove mass, decrease cerebral edema- bone flap, osmotic diuretic (mannitol, 3% hypertonic saline)
To decrease blood volume
Correct obstruction of venous outflow (Head midline)
Normal CO2 levels (CO2 levels = vasoconstriction = cerebral blood volume = ischemia)
To decrease CSF
drain it (external ventricular drain)
Cerebral blood flow definition
The amount of blood in milliliters passing through 100 g of brain tissue in 1 minute
About 50 mL/min per 100 g of brain tissue
Cerebral blood flow autoregulation
Adjusts diameter of blood vessels
Ensures consistent CBF
Only effective if mean arterial pressure (MAP) 70 to 150 mm Hg
Cerebral perfusion pressure
CPP = MAP – ICP
Normal is 60 to 100 mm Hg. (less than 30 incompatable with life)
<50 mm Hg is associated with ischemia and neuronal death.
Effect of cerebral vascular resistance- CPP = Flow x Resistance
cerebral blood flow pressure changes
Compliance is the expandability of the brain.
Impacts effect of volume change on pressure
Compliance = Volume/Pressure
Stages of Increased ICP
Stage 1:total compensation
Stage 2: ↓compensation; risk for ↑ICP
Stage 3: failing compensation; clinical manifestations of ↑ICP (Cushing’s triad)
Stage 4: Herniation imminent → death
Factors affecting cerebral blood vessel tone
CO2
O2
Hydrogen ion concentration
Cushings triad
Hypertension, bradycardia, irregular RR= Herniation
Types of cerebral edema
vasogenic, cytotoxic, interstitial
Vasogenic cerebral edema
Most common type Occurs mainly in white matter Fluid leaks from intravascular to extravascular space. Variety of causes Continuum of symptoms → coma
Cytotoxic Cerebral Edema
Disruption of cell membrane integrity
Secondary to destructive lesions or trauma to brain tissue
Fluid shift from extracellular to intracellular
Interstitial Cerebral Edema
Usually result of hydrocephalus
Excess CSP production, obstruction of flow, or inability to reabsorb
Treat with ventriculostomy or shunt
Decrease motor function with increase ICP
Hemiparesis/hemiplegia Decerebrate posturing (extensor)- Indicates more serious damage Decorticate posturing (flexor)
Tentorial herniation
Tentorial herniation (central herniation) occurs when a mass lesion in the cerebrum forces the brain to herniate downward through the opening created by the brainstem.
Uncal herniation
with lateral and downward herniation.
Cingulate herniation
with lateral displacement of brain tissue beneath the falx cerebri.
Diagnostics for ICP
CT scan / MRI / PET
EEG
Cerebral angiography
ICP and brain tissue oxygenation measurement (LICOX catheter)
Doppler and evoked potential studies
NO lumbar puncture- cerebral herniation could occur from the sudden release of the pressure in the skull from the area above the lumbar puncture.
Ventriculostomy
Catheter inserted into lateral ventricle (used to drain)
Coupled with an external transducer (wave forms of brain) measures ICP
Fiberoptic catheter
Sensor transducer located within the catheter tip, measures ICP
Subarachnoid bolt or screw
Between arachnoid membrane and cerebral cortex, measures ICP
Inaccurate readings of ICP caused by
CSF leaks Obstruction in catheter/ kinks in tubing Differences in height of bolt/transducer Incorrect height of drainage system Bubbles/air in tubing
LICOX catheter
Measures brain oxygenation (PbtO2) and temperature.
Placed in healthy white brain matter.
Jugular venous bulb catheter
Measures jugular venous oxygen saturation (SjvO2).
Drug therapy for ICP
Corticosteroids (Vasogenic edema) Antiseizure medications Antipyretics Sedatives Analgesics Barbiturates
Nutrition for increased ICP
Hypermetabolic and hypercatabolic state ↑ need for glucose
Enteral or parenteral nutrition
Early feeding (within 3 days of injury)
Keep patient normovolemic.
IV 0.9% NaCl preferred over D5W or 0.45% NaCl
Interventions to optimize ICP and CPP
HOB elevated appropriately Prevent extreme neck flexion. Turn slowly. Avoid coughing, straining, Valsalva. Avoid hip flexion.
spinal cord
Approximately 45 cm (18 inches) long
Thickness comparable to finger
Extends from foramen magnum at base of skull to lower border of first lumbar vertebrae where it tapers to fibrous bands
Nerve roots extend below 2nd lumbar space
Mechanism of Spinal Injury
Flexion Hyperextension Flexion-rotation Extension-rotation Compression
Flexion injury
occur when the head is suddenly & forcefully accelerated forward, causing extreme flexion of the neck.
occurs in head-on collisions & diving accidents.
typically seen in the C5-6 area of the cervical spine
Hyperextension injury
are frequently acceleration injuries as are seen in rear-end collisions or as the result of falls in which the chin is forcibly struck.
C4-5 is the area of the spine most commonly affected.
Compression injury
(Axial loading) cause the vertebra to squash or burst.
They usually involve high velocity and affect both the cervical and thoracolumbar regions of the spine.
Blows to the top of the head and forceful landing on the feet or buttocks can result in compression injury.
Rotation injuries
caused by extreme lateral flexion or twisting of the head & neck.
The tearing of ligaments can easily result in dislocation as well as fracture, & soft tissue damage frequently complicates the primary injury.
Extent of neurologic damage caused by spinal cord injury results from
Primary injury damage
-Actual physical disruption of axons
Secondary damage
-Ischemia, hypoxia, microhemorrhage, and edema
Because secondary injury processes occur over time, the extent of injury and prognosis for recovery are most accurately determined 72 hours or longer after injury.
Secondary injury
Hypo-perfusion Decreased Circulation Decreased Blood Flow Vasospasm Demyelinated Axons
Complete injury
Results in a total loss of sensory/ motor function below the level of injury.
Complete dissection of the spinal cord and its neurochemical pathways.
Paraplegia Tetraplegia
Paraplegia
paralysis of the lower portion of the body, sometimes involving the lower trunk. Injury occurs in the thoracolumbar region (T2 to L1).
Tetraplegia
(formerly called quadriplegia) impaired function of the arms, trunk, legs, and pelvic organs. Injury occurs from the C1 to T1 level.
Incomplete injury
Some function remains below the level of injury.
Syndromes Associated with incomplete lesions
Central cord syndrome Anterior Cord Syndrome Posterior cord Syndrome Brown – Sequard Syndrome Conus Medullaris Syndrome and Cauda Equina Syndrome.
Central cord syndrome-
damage primarily to the central gray or white matter of the spinal cord.
Results from edema formation that occurs in response to the primary injury.
The resulting motor deficit is more severe in the upper extremities than in the lower.
The sensory impairment is variable. Improvement over time is expected.
Anterior Cord Syndrome
typically results from injury or infarction involving the anterior spinal artery, which perfuses the anterior two thirds of the spinal cord.
The resultant damage includes motor paralysis with loss of pain & temperature sensation noted below the level of the lesion.
Still have touch and vibration sense
Posterior Cord Syndrome
extremely rare syndrome in which proprioreceptive sensation of position and vibration are lost due to damage to the posterior columns of the spinal cord.
Brown-Sequard Syndrome
results from a unilateral injury, usually of the penetrating type, that involves just half of the spinal cord.
There is a resulting loss of motor ability plus touch, pressure, and vibration sensation on the same side as the injury but loss of pain and temperature sensation on the opposite side.
Conus Medullaris Syndrome and Cauda Equina Syndrome
Damage to the very lowest portion of the spinal cord (conus) and the lumbar sacral nerve roots (cauda equina).
Results in flaccid paralyisi of the lower limbs and areflexic (flaccid) bladder and bowel.
Level of injury (segments)
Upper cervical (C1-C2) Lower cervical (C3-C8) Thoracic (T1-T12) Lumbar (L1-L5) Sacral (S1-S5)
Autonomic Nervous System Syndromes
Spinal Shock Neurogenic Shock (warm/ brady)
Spinal Shock
- This is the temporary suppression of reflexes below the level of injury
- SCI interrupts stimulation that keeps neurons ready.
- Over time spinal neurons gradually regain excitability, which ends spinal shock. (hours to weeks)
- has long-term effects on sensation and voluntary movement
- Functions controlled by spinal reflex arcs do not depend on communication with the brain, & the impact on these functions is limited to spinal shock.
Neurogenic Shock
- Pts with severe cervical and upper thoracic injuries.
- hemodynamic instability caused by the loss of innervation from the brain to the SNS.
- The loss of sympathetic outflow allows the PNS to be engaged unopposed.
- The parasympathetic influence results in hypotension from peripheral vasodilation, severe bradycardia, & hypothermia.
Autonomic Dysreflexia
Massive, uncompensated cardiovascular reaction
Exaggerated sympathetic response
Seen after Spinal Shock (above T6)
Triggered by Distended bladder or bowel or Pressure ulcers
INCREASED BP (300 sys), Severe headache, Increased sweating, Decreased HR, Cool skin below injury, flushing, blurred vision, & nasal congestion
If injury to C5 or higher
may need to be intubated in field
Be aware of potential Bradycardia
May need atropine
Diagnostic test for spinal cord injury
Standard x-rays- can demonstrate fracture or dislocation of the vertebral bodies or spinal processes
Computed tomography (CT)- used to further evaluate areas of the spine that may be injured but cannot be adequately visualized on standard x-ray
Magnetic resonance imaging (MRI)- MRI shows bone poorly but provides excellent visualization of the spinal cord and nerve roots. Identify contusion or hemmorhage
Medications for Spinal cord injury
methylprednisolone (Solu-Medrol)- within 8hrs or not at all
Corticosteroids- to decrease edema of the cord
Vasopressors- to treat bradycardia or hypotension due to spinal shock
Antispasmodics- to treat spasticity
Analgesics- to reduce pain
Histamine H2 antagonists- to prevent stress-related gastric ulcers
Stabilization of Spinal cord injury
Placed in fixed skeletal traction to realign the vertebrae
Halo fixation device & cervical tongs (Gardner-Wells, or Crutchfield) which may be used in conjunction with a Stryker frame or kinetic treatment table.
Surgery for spinal cord injury
Used to release compression, correct alignment, and improve the stability of the spine.
The procedure is usually necessary to remove bone fragments, evacuate a hematoma, or remove penetrating objects such as a bullet.
Other surgeries could be a decompression laminectomy, a spinal fusion, and insertion of metal rods (Harrington rods, “CD” rods).
If the skull pins become displaced
the head should be held in a neutral position and physician contacted
If halo traction is used, the nurse should teach the patient to:
wash the skin daily under the lamb’s wool liner of the vest
use a straw for drinking
explain to the patient that they cannot drive (device impairs the range of vision)
Cardiovascular Instability with spinal cord injury
Because of unopposed vagal response, the heart rate is slowed.
Any increase in vagal stimulation (suctioning) can result in cardiac arrest.
Loss of sympathetic tone in peripheral vessels results in decrease blood pressure.
Lack of muscle tone to aid venous return can result in sluggish blood flow and predispose the patient to DVT.
Treatment of Autonomic Dysreflexia
Elevate the head of the bed
Notify the physician
Monitor B/P as frequently as every 1-2 minutes
Check patency of urinary catheter or insert bladder catheter
Check rectum for stool
G and 4 p’S
Greif and depression Prevent Complications of Disuse Protect the Skin Pee Poop Sex
Living Donors
Kidney, Lobe of Liver (donor liver will regenerate), Lobe of Lung (Donors lung does not regenerate)
Ideally is related to the recipient.
Blood relative, emotionally related, living donor, altruistic living donor or paired organ donation
Related donors are preferred:
Increased histocompatibility
Increased Human Leukocyte Antigen (HLA) matching
Results in a longer graft life
Cadaver Donor
Donors who die of cardiac death (death by termination of cardiac & respiratory function)- transplantable tissues may be limited to heart valves, corneas, eyes, saphenous veins, skin, & bones (kidneys, liver, pancreas)
Donors who die of brain death (cessation of the entire brain and brain stem function)- transplantable tissues include tissues, as well as solid organs: kidneys, lungs, heart, liver, pancreas, and small bowel
Graft
transfer of tissue from one part of the body to a different part or from another donor source
There are 3 major types of grafts:
Autograft, Heterograft, Allograft
Autograft
Transplantation of tissue from one part of a person’s body to another part
Heterograft
Transplantation of tissues between 2 different species
Allograft
Tissue that is transplanted between members of the same species
Isograft (syngraft)
Transplantation between identical twins, type of allograft
Factors for matching donors
ABO blood typing, Crossmatch, HLA – Human Leukocyte Antigen
Other factors: medical urgency, time on waiting list, geographic location.
ABO typing
identifies the blood group of the donor and the recipient. ABO compatibility is an initial criteria for transplantation.
Type AB- universal organ recipient
Type O- universal donor type
RH factors do not have to be the same.
Crossmatching
tests the potential recipient for antidonor (preformed) antibodies
A positive crossmatch means we can not transplant indicates a hyperacute rejection will occur.
The recipient’s body has developed antibodies that react against your donor’s organs and their cells.
Prior transplants increased the risk for a positive crossmatch
Human Leukocyte Antigen System
Antigens responsible for rejection of genetically unlike tissues are called major histocompatibility antigens (MHC)
In humans they are called the Human leukocyte antigen (HLA) system. present on all nucleated cells and platelets
The proteins encoded by the genes are called antigens
An entire set of these genes (A, B, C, D and DR) genes are termed a haplotype.
In organ transplant A, B and DR are used for compatibility matching.
Each locus has two alleles that encode for antigens so a total of 6 antigens are identified
Donor-Recipient Compatibility Testing- Tissue Typing
identification of the HLA (human leukocyte antigen) antigens of both the donor and the recipient.
evaluates the degree to which the 2 sets of tissues are HLA matched
Some transplants are not as dependent on HLA matching as others:
Kidneys HLA matching very important
Heart and Lungs – in the middle
Liver –not as important
Panel of Reactive Antibodies (PRA)
The recipients serum and a randomly select panel of Donor’s lymphocytes is mixed together to determine reactivity.
The recipient may have been exposed to HLA antigens by blood transfusions, pregnancy or previous transplant.
A high PRA indicates a poor chance of finding a crossmatch –negative donor.
Plasmapheresis and IV IG have been done to lower the number of pre-formed antibodies in highly sensitized patients.
The criteria used for determination of need in organ transplant
End-stage organ failure Short life expectancy (6-12 months) Severe functional disability No additional serious health problems Psychological readiness
Factors evaluated prior to placing the patient on the national patient waiting list for organ transplantation:
Clinical status
Nutritional Status
Psychological status
Financial status- meds are expensive
Candidacy Exclusion for organ transplant
Morbidly Obese, Continued smoking
Co-Morbidities: Disseminated malignancies, Refractory or untreated cardiac disease, Chronic respiratory failure, Extensive vascular disease, Chronic infection, Psychosocial disorders (Non-adherence, alcoholism, drug addiction)
United Network for Organ Sharing
Once the decision is made to accept a patient as a suitable recipient, the patient’s name & vital information are entered into the computer bank at the United Network for Organ Sharing
organ preservation
Heart and lungs- 4 to 6 hours
Liver, intestines, and pancreas- 6 to 12 hours
Kidneys- up to 72 hours, prefer less than 24
Pre-op for kidney heart and liver
Usually only a matter of hours and includes:
Comprehensive lab studies
Chest x-ray
ECG
Dialysis within 24 hours of transplantation for kidney transplant, Label dialysis access site (fistula) so it will not be disturbed during surgery.
Stress that dialysis may be needed post-op and does not indicate failure.
End Stage Renal Disease
primary indicator for transplant can result from (3 most common): hypertension, Diabetes mellitus glomerulonephritis
Post-op managment transplant
IV fluids at a rate sufficient to keep UO > 100 mL/hr Diuretic therapy Daily weights Vital signs & CVP monitoring Prophylactic antibiotic therapy
Post op transplant urine output
may have large volume urine output due to new kidney’s ability to filter BUN
The volume of fluids administered during surgery
Initial tubular dysfunction and inability to concentrate urine
Urine output can be as high as 1L/hr during this phase and will gradually decrease as BUN and creatinine return to normal.
Urine output is replaced ml for ml with IV fluids for 12 -24 hours
CVP is measured to maintain homeostasis and intravascular volume
Post op transplant concerns
- Acute Tubular Necrosis- Prolonged cold times, Cadaver donor, May require dialysis
- Decreased urine output- Dehydration, Obstruction, Urine Leak, Obstruction (blood clot- May require gentle irrigation, must be prescribed)
- hypertension- kidney transplant
Major indications for heart transplant
- End Stage Heart failure refractory to optimal medical management
- Cardiomyopathy
- Valvular heart disease- Severe decompensated, inoperable
- Ventricular aneurysm
- Congenital malformations
- Any cardiac abnormality that severly limits normal function and /or has a 50% mortality rate at 2 years.
Contraindications for heart transplant
Absolute- age >70, Less than 5 year life expectancy due to other illness, Advanced cerebral or vascular disease, Active infection, Severe pulmonary disease
Relative- Uncontrolled diabetes, Irreversible kidney or liver dysfunction, Morbid obesity, Active substance abuse, Non compliance, Psychological impairment, Lack of social support, Unrealistic expectations
Post- op heart transplant effects of denervation
- During removal of the donor heart, the nerve supply is severed, loss of vagal influence= the resting sinus rate is between 90 and 110 bpm
- increased body metabolic demands causes increase heart rate, contractility, & CO by release of circulating catecholamines from the adrenal medulla
- prevents transmission of pain impulses from ischemic myocardium to the brain
- ECG stress testing and annual coronary angiography or coronary vascular ultrasonography are usually performed
Major indications for liver transplant
Chronic irreversible liver disease
Liver & biliary tree primary malignant tumors
Fulminant hepatic failure
Cirrhosis is the most common indicator for transplantation in adults
Monitor post op liver
Monitor bile drainage appearance & quality
Monitor lab tests that reflect liver function:
Prothrombin time (PT), partial thromboplastin time (PTT)
Alanine aminotransferase (ALT) & aspartate aminotransferase (AST), alkaline phosphatase
Bilirubin (total & direct), ammonia levels
Glucose
Monitor neurologic status
Postop complications of liver transplant
Technical Complications: Thrombosis, Bleeding, Anastomosis Leakage
Graft Rejection: Hyperacute, Acute, Chronic
Immunosuppressant-Related Problems: Infection, Organ Dysfunction, Malignancy, Steriod Induced Problems
Vascular Thrombosis
development of a blood clot in the vascular system- as a complication of organ transplantation, it refers to a blood clot in the vasculature of the graft, often the major artery
Early detection and immediate thrombectomy are essential if the graft is to survive
Anastomosis Leakage
refers to the site at which the graft is sutured into the recipient. Problems at the anastomosis site usually occur 1 to 3 weeks following transplantation. Anastomosis leaks usually require surgical exploration and repair.
Graft Rejection
refers to the activation of the immune response against a transplanted tissue or organ.
result of the body recognizing the new tissue as nonself, which then triggers an autoimmune system attack to eliminate the invader.
primarily due to T lymphocyte and B lymphocyte activities.
3 types of graft rejection: Hyperacute, Acute, Chronic
Hyperacute rejection
Occurs in the OR immediately after transplantation
It is a humoral response in which the B lymphocytes are activated to produce antibodies
It results from the presence of preformed graft-specific cytotoxic antibodies
Because the antibodies are already formed, as soon as the graft is placed, the immune system recognizes the foreign tissue & increases graft-specific antibody production
Uncommon due to pre-transplantation cross-matching
Acute Rejection
Occurs within the first 3 months after transplantation
The most common type of rejection, & most patients experience at least one episode
It is a cell-mediated immune response in which the T lymphocytes attack and destroy the graft tissue.
The type of rejection that responds best to immunosuppressive therapy-Corticosteroid, Polyclonal or Monoclonal Antibodies
Chronic rejection
A humoral immune response in which antibodies slowly attack the graft
Usually occurs from 3 months to years after transplantation & is accompanied by deteriorating organ function
It is irreversible
Treatment of rejection
- Hyperacute (Immediate) Rejection– remove organ
- Acute Rejection – (First 3 months)- Additional immunosupressive therapy
- Chronic Rejection (after 3 months)- No definitive treatment., Change immunosupressive therapy to include tacrolumus (Prograft) or mycophenolate mofetil (CelCept), Mainly supportive and re-transplant
Immunosuppressive Therapy
Most patients are initially on triple therapy: A calcineurin inhibitor, A corticosteroid, Mycophenolate mofetil (CellCept)
Types of Immunosuppressents
Calcineurin inhibitors Corticosteroids Cytotoxic Agent- Mycophenolate mofetil (CellCept) Polyclonal antibodies Monoclonal Antibodies
Calcineurin Inhibitors:
Cyclosporin (Sandimmune, Neoral, Gengraf)
Avoid Grapefruit Juice
Tacrolimus (Prograf, FK506)
These are the most effective immunosuppressants available, prevent a cell-mediated attack against the transplanted organ
These drugs are associated with multiple serious side effects- Nephrotoxicity, Hepatotoxicity, Lymphoma,Htn, Hirsutism, Leukopenia, Gingival hyperplasia
Cytotoxic Agents:
Decreases activity of T and B cells -Mycophenolate Mofetil- (CellCept) Diarrhea, N & V, severe neutropenia, thrombocytopenia, increase incidence of malignancies
- Cyclophosphamide- (Cytoxan, Neosar)
- Azathioprine- (Imuran)
- Sirolimus (Rapamune) [renal transplant]
Monoclonal antibodies:
increase the specificity of attack by targeting the lymphocyte subsets responsible for the immune rejection reaction
Muromonab-CD3 (Orthoclone OKT3)
Daclizumab (Zenapax)
Basiliximab (Simulect)
Polyclonal antibody:
Target T lymphocytes
Lymphocyte immune globulin (Atgam)
Belatacept (Nulojix) – prevents activation of T cells
Graft-Versus-Host Disease (GVHD)
Occurs when an immunoincompetent patient receives immunocompetent cells.
the graft (transplanted tissue) that rejects the host (recipient’s tissue)
Donor T cells attack and destroy vulnerable host cells
Involves skin (rash), liver (jaundice to hepatic coma) and GI tract (diarrhea, pain, GI bleed and malabsorption)
Biggest problem is infection (bacterial and fungal)
Diabetic Ketoacidosis (DKA)
Caused by profound deficiency of insulin
Characterized by: Hyperglycemia, Ketosis, Acidosis, Dehydration
Most likely to occur in type 1 diabetes (illness that get BS out of control)
Precipitating factors of DKA
Illness or other stressor, Infection, Inadequate insulin dosage, Undiagnosed type 1 diabetes, Poor self-management
Clinical Manifestations of DKA
Often sudden onset
Dehydration, weight loss, Tachycardia, Orthostatic hypotension, Lethargy and weakness early
Abdominal pain, anorexia, n/v, Kussmaul respirations, fruity breath odor, BS of 250 mg/dL or higher, Blood pH lower than 7.30, Serum bicarbonate less than 16 mEq/L
Increased ketone levels in urine and serum
Hyperkalemia with acidosis; total body potassium low
Severity of acidosis determines LOC
Treatment of DKA
Give O2, IV access; begin fluid resuscitation (NaCl, 0.45%- 2nd to prevent cerebral and pulm edema or 0.9%- 1st vasculaur hydration)
Add 5% to 10% dextrose when blood glucose level approaches 250 mg/dL
Continuous regular insulin drip, 0.1 U/kg/hr.
Potassium replacement as needed if creatinine is normal (no more than 20 meq/ hr on pump)
ECG monitoring, Vital sign monitoring
Hyperosmolar Hyperglycemic Syndrome (HHS)
Life-threatening syndrome, type 2 diabetes
Does not occur as fast as DKA
Enough circulating insulin to prevent ketoacidosis
Fewer symptoms lead to higher glucose levels (>600 mg/dL)
More severe neurologic manifestations because of ↑ serum osmolality
Ketones absent in blood and urine
Dehydration
HHS precipitating factors
UTIs, pneumonia, sepsis
Acute illness
Newly diagnosed type 2 diabetes
Impaired thirst sensation and/or functional inability to replace fluids
HHS symptoms
Glycosuria
Polyuria and then later oliguria as dehydration worsens
Hypotension and tachycardia
Do not have ketonuria
Electrolyte disturbances
Decrease LOC (can progress to coma), alteration in sense of awareness, seizures, hemiparesis
Possibly hypovolemic shock
HHS treatment
Medical emergency= High mortality rate
Replacing fluids is top priority (NS or ½ NS)
NS with IVP (reg) insulin and possibly later an insulin drip
Frequent checks of BG
KCL replacement due to K lost with polyuria (start K replacement as soon as UOP is satisfactory) (monitor for elec. Imbalances and correct as indicated)
Monitor ECG, BUN, creatinine, BMP
Insulin administered at lower rate than DKA because have endogenous insulin
Cortex
The outer layer (gland) is the CORTEX secreting steroid hormones: Glucocorticoids (cortisol, cortisone and corticosterone), Mineralcorticoids (aldosterone)- retain Na and H2O, Androgens (testosterone, estrogen)
Medulla
The middle center (gland) is the MEDULLA secreting
Neurotransmitters epinephrine and norepinephrine, which are catecholamines (increase BP)
Glucocorticoids (Cortisol)
Increase blood sugar levels
Involved in the breakdown of fats and proteins- Muscle wasting and poor wound healing
Critical to the stress response
Anti-inflammatory and immunosuppressive
Mineralocorticoids (aldosterone)
Potassium and sodium balance
Increase sodium and water reabsorption
Increase excretion of potassium and hydrogen
Secreted in response to low serum volume, high serum osmolality
Secreted in response to low serum sodium levels and high serum potassium levels
Androgens (testosterone)
Adrenal cortex steroid hormones
Androgen contributes to: Growth and development in both genders, Sexual activity in adult women
Primary hyperfunction of the adrenal cortex
from adrenal gland, decrease in CRH and ACTH, increase cortisol
Secondary Hyperfunction of the adrenal cortex
from pituitary, decrease in CRH, increase in ACTH and cortisol
Tertiary Hyperfunction of adrenal cortex
from hypothalamus, decrease in ACTH, increase in CRH and cortisol
Control of cortisol levels
Corticotropin releasing hormone (CRH) is secreted by the hypothalamus
Stimulates the anterior pituitary to release ACTH
Stimulates the adrenal cortex to release glucocorticoids (cortisol)
Feedback loop: increased cortisol levels decrease the secretion of CRH and ACTH
Cushing Syndrome Etiology and Pathophysiology
Caused by excess of corticosteroids
Iatrogenic administration of exogenous corticosteroids
ACTH-secreting pituitary adenoma
Termed Cushing’s Disease when excess glucocorticoids is secondary to pituitary
Adrenal tumors- secrets hormons
Ectopic ACTH production by tumors
Cushing Syndrome Clinical Manifestations
Truncal obesity with thin extremities, Moon face , Purplish red striae, hirsutism (hair growth), Menstrual disorder, Htn, Hypokalemia, hypernatremia
*Hyperpigmentation of skin if ACTH is high (Cushing’s disease) in creases
Excess glucocorticoids in Cushing’s
Weight gain from accumulation of adipose tissue and excess fluid retention
Hyperglycemia related to glucose intolerance and ↑ gluconeogenesis
Muscle wasting → weakness
Hypocalcemia, loss of bone matrix → osteoporosis and back pain
Loss of collagen → thin skin, easily bruises, Delay in wound healing
Irritability, Anxiety, Euphoria, Psychosis
Mineralocorticoid excess and Adrenal androgen excess in Cushing’s
Mineralocorticoid excess → hypertension
Adrenal androgen excess → Severe acne, Virilization in women, Feminization in men
Cushing Syndrome Diagnostic Studies
- Plasma cortisol measurement, 24-Hr urine collection for free cortisol, Low-dose dexamethasone suppression test, Urine 17-ketosteroid measurement, CT scan, MRI
- Plasma ACTH levels
- High or normal with Cushing disease (pituitary etiology)
- Low or undetectable with Cushing syndrome
- Hypokalemia and alkalosis
- With ectopic ACTH syndrome
Cushing Syndrome Treatment
Normalize hormone secretion
Treatment depends on cause
Surgical removal or irradiation of pituitary adenoma
Adrenalectomy for adrenal tumors or hyperplasia
Removal of ACTH-secreting tumor (through gum)
Diet prescription- Low cal, Carbs, Na+, lipids, and cholesterol, High protein, High Vitamin D, High K+
Fluid restriction
If cause of Cushing’s is iatrogenic
Gradually discontinue therapy
Decrease dose
Convert to an alternate-day regimen
Dose must be tapered gradually to prevent adrenal insufficiency
Post- op care with Cushing’s
↑ Risk of hemorrhage (adrenal gland highly vascular)
Large release of hormones into circulation → instabilities in BP, fluid balance, and electrolyte levels
Monitor VS, daily weights, electrolytes, glucose levels
Notify HCP if UOP less than 30 ml/hr
High doses of corticosteroids administered IV during and several days after surgery
Risk for htn and subsequent hemorrhage
Cushing’s post op adrenal
Monitor for acute adrenal insufficiency:
Vomiting, increased weakness, Dehydration, hypotension, Painful joints, Pruritus, Peeling skin, Severe emotional disturbances
Primary Hyperaldosteronism Etiology and Pathophysiology
Solitary adrenocortical adenoma (most common cause), Genetic link
Excessive aldosterone secretion- Sodium and water retention, Potassium and hydrogen ion excretion
Hypertension with hypokalemic alkalosis
Also called Conn’s Syndrome
Secondary hyperaldosteronism
Nonadrenal cause:
Renal artery stenosis, Renin-secreting tumors, Chronic kidney disease
Clinical Manifestations hyperaldosteronism
Hypernatremia, hypertension, headache, No edema, Nocturia, Polydipsia, polyuria, paresthesias, visual changes, Hypokalemia- Muscle weakness, Fatigue, Cardiac dysrhythmias, Metabolic alkalosis
Hyperaldosteronism Diagnostic Studies
Primary aldosteronism
↑ Plasma aldosterone levels ↑ Sodium levels ↓ Potassium levels ↓ Renin activity
CT scan or MRI
Plasma 18-hydroxycorticosterone level
Treatment of Hyperaldosteronism
*Adrenalectomy to remove adenoma
Preoperative- K-sparing diuretics Spironolactone (Aldactone), Antihypertensives, Oral K supplements, Sodium restrictions
*Bilateral adrenal hyperplasia- K-sparing diuretic to block aldosterone synthesis, Calcium channel blockers to decrease BP, Dexamethasone to decrease hyperplasia
Primary Hypo-dysfunction of adrenal cortex
from adrenal, increase ACTH and CRH, decrease cortisol
Secondary Hypo-dysfunction of adrenal cortex
from pituitary, increase CRH, decrease ACTH and cortisol
Tertiary hypo-dysfunction of the adrenal cortex
from hypothalamus, decrease in CRH ACTH and cortisol
Hypofunction
Primary- Addison’s disease, Lack of glucocorticoids, mineralocorticoids, and androgens
Secondary- Lack of pituitary ACTH, Because of pituitary disease or suppression of the hypothalamic-pituitary axis because of the administration of exogenous corticosteroids, Lack of glucocorticoids and androgens
Addison’s Disease causes
- Most common cause of Addison’s disease in the US is autoimmune response against adrenal cortex
- Often other endocrine conditions are present as well as Addison’s disease
- Addison’s disease can also be caused by TB, infarction, fungal infections (histoplasmosis), AIDS, metastatic cancer
- Iatrogenic Addison’s disease due to Adrenal hemorrhage from anticoagulant therapy, chemotherapy, Bilateral adrenalectomy
Clinical manifestations of Addison’s Disease
Not evident until 90% of adrenal cortex is destroyed and therefore disease may be advanced before it is diagnosed, Insidious onset: Progressive weakness, Fatigue, Weight loss, Anorexia, loss of androgen, hyperpigmentation
Orthostatic hypotension, Hyponatremia and salt craving, Hyperk, N/v, abdominal pain, Diarrhea, fever, Irritability, depression, emotional liability, Emaciation, Decreased resistance to stressors, Hypoglycemia
Addison’s Crisis
Acute adrenal insufficiency, Insufficient or sudden, sharp decrease in hormones, Life-threatening
Various triggers:
Stress (infection, surgery, psychological distress), Sudden withdrawal of corticosteroid therapy, Adrenal surgery, Sudden pituitary gland destruction
Diagnostic for adrenal insufficiency
*↓ Serum and urinary cortisol
*24 hour urine collection
*ACTH levels
-↑ In primary adrenal insufficiency (Addisons)
-↓ In secondary adrenal insufficiency
*ACTH stimulation test
-Distinguishes between primary and secondary disease
Primary adrenal insufficiency is confirmed when cortisol levels fail to rise over basal levels with an ACTH stimulation test
Lab changes in adrenal insufficiency
↓ Urinary cortisol and aldosterone ↑ Potassium ↓ Chloride, sodium, glucose Anemia ↑ BUN (due to dehydration) ECG changes CT scan, MRI
Treatment for adrenal insufficiency
Correct underlying cause, Correct and prevent dehydration, Hormone therapy, Hydrocortisone, increase during periods of stress, Fludrocortisone (Florinef) (mineralocorticoid), Vasopressors to raise BP, Diet that is high Na+, high fluid intake, high carb, high protein, low K+
Rest because patient is easily fatigued
Treatment for Addison’s Crisis
Shock management (hypovolemic) High-dose hydrocortisone replacement 0.9% saline solution and 5% dextrose-large volumes of IVF are administered to reverse hypotension and electrolyte imbalances until BP returns to normal
Medication Dosing for Addison’s
Glucocorticoids in divided doses (2/3 in the morning and 1/3 in the afternoon), Mineralocorticoids once in the morning, Reflects normal circadian rhythm, Decreases side effects of corticosteroids
Need to increase corticosteroids during times of stress (physical or emotional)
Emergency Kit for adrenal insuficency
Contains 100 mg of IM hydrocortisone, syringes
Instruct patient and family how to administer IM hydrocortisone
Corticosteroid Therapy side effects
↓ Potassium and calcium- Hypocalcemia is related to the anti-Vitamin D effect of corticosteroids
↑ Glucose and BP
BP increases due to excess blood volume and vasoconstrictor effects of corticosteroids
Suppressed immune response, Thin skin that is easily broken, Peptic ulcer disease, Muscle atrophy/weakness, Mood and behavior changes, Moon face, truncal obesity, Protein depletion, Predisposition for pathological fractures, 0steoporosis, Risk for acute adrenal insufficiency if therapy is stopped abruptly
Pheochromocytoma Etiology and Pathophysiology
Caused by a tumor of the adrenal medulla
Produces excessive catecholamines (epinephrine and norepinephrine)
Mostly in young to middle-aged adults
Results in severe hypertension
Pheochromocytoma Clinical Manifestations
Severe, episodic htn, Pounding ha, visual disturbances, Tachycardia with palpitations, Profuse sweating, pallor, tremors, anxiety, Abdominal or chest pain, N/v, weight loss, Hyperglycemia, glucosuria, polyuria
Diagnosis is often missed
Pheochromocytoma Diagnostic Studies
Urinary vanillylmandelic acid (VMA) test- VMA is breakdown product of catecholamine metabolism, Normal is 1-5 mg, elevated with tumor
Collect 24 hour urine, ice or refrigerate
Plasma catecholamines are elevated
CT and MRI used for tumor localization
Pheochromocytoma Treatment
Surgical removal of tumor
Calcium channel blockers control BP
Sympathetic blocking agents may- ↓ BP and ↓ Symptoms of catecholamine excess
Beta blockers to ↓ dysrhythmias (propranolol or Inderal)
Apresoline (Hydralazine) for hypertensive crisis
Bathe frequently (sweating) but avoid chilling
Avoid coffee, tea, cola
Medications for Pheochromocytoma
Alpha adrenergic blocker- Phenoxybenzamine (Dibenzyline), Give 7-10 days preoperatively to decrease BP
Beta blockers- Propranolol to decrease HR and dysrhythmias, Start after BP controlled with alpha blockers
