Metabolic Diseases Flashcards
Formula for serum osmolality
OSM=2Na+Glucose/18+BUN/3 in mg/dL
What is the normal serum osmolality?
270-290 mOsm/mL
True or False. the brain may be damaged, even to an irreparable degree, by a disturbance of blood chemistry (e.g., hypoglycemia, hypoxia) that has vanished by the time the patient is examined
TRUE
What are the medical conditions that lead to ischemic-hypoxic encephalopathy?
- global reduction in cerebral blood flow
- Hypoxia from suffocation
- diseases that paralyze the respiratory muscles ( or damages the medulla and leads to
failure of breathing - carbon monoxide (CO) poisoning
What is the ultimate determinant of the adequacy of oxygen supply to organs?
product of blood oxygen content & cardiac output
What determines blood oxygen content?
Hemoglobin concentration &
O2 saturation %
How much is the hemoglobin O2 saturation at normal pH and temperature, partial pressue of 60mmHg? At 40mmHg?
@ 60mmHg = 90%
@ 40mmHg = 75%”
The parts of the nervous system which are most vulnuerable to hypoxia are:
1 CA1 of hippocampus
2 cerebellar Purkenje cells
3 striatal neurons
4 Cortical Layers 3 5 6
The parts of the nervous system which are resistent to hypoxia are:
nuclear structures of the brainstem and spinal cord
True or False. degrees ofhypoxia that at no time abolish consciousness rarely, if ever, cause permanent damage to the nervous system.
TRUE
True or False. Subnormal body temperatures, greatly prolong the tolerable period of hypoxia
TRUE
What connotes a more favorable prognosis for patients with anoxia?
intact brainstem function as indicated by normal pupillary light and ciliospinal responses, induced by passive head turning (doll’s eye movements), and other
vestibula-ocular reflexes
4 Signs of grave prognosis in anoxic patients:
after Day 1 absence of the following: 1 absent corneal response 2 absent pupillary reactivity 3 no withdrawal to pain 4 absence of any motor response
The most common early change in neuroimaging studies of patients with severe hypoxic injury:
loss of gray-white matter distinction
The 7 permanent neurologic sequelae or posthypoxic syndromes observed most frequently are as follows:
- Persistent comaor stupor
- With lesser degrees of cerebral injury, dementia with
or without extrapyramidal signs - Extrapyramidal (parkinsonian) syndrome with cognitive
impairment (discussed in relation to CO poisoning) - Choreoathetosis
- Cerebellar ataxia
- Intention or action myoclonus (Lance-Adams syndrome)
- An amnesic state
Syndrome of initial improvement after hypoxia/anoxia followed by apathy, confusion, irritability, agitation or mania after 1-4 weeks
Delayed Postanoxic Encephalopathy and Leukoencephalopathy
What is Lance Adams Syndrome?
delayed movement-induced myoclonic and ataxic tremor after an anoxic episode
Carbon Monoxide affinity to hemoglobin is ____ times more than oxygen
200x
Half life of carbon monoxide?
5 hours
Symptoms of carbon monoxide poisoning when the carboxyhemoglobin reaches 20-30%
headache, nauseam dyspnea, confusion, dizziness, clumsiness
Symptoms of carbon monoxide poisoning when the carboxyhemoglobin reaches 50-60%
coma, decerebrate, decorticate, seizures
generalized EEG slowing
Symptoms of carbon monoxide poisoning when the carboxyhemoglobin reaches slightly higher than 30%
blindness, visual defects papilledema
Delayed neurologic deterioration after CO poisoning
extrapyramidall symptoms (parkinsonian, bradykinesia)
Characteristic lesions in neuroimaging of patients with CO poisoing
can be normal
globus pallidus
putamen
Treatment of CO poisoning
hyperbaric oxygen
The protein that is said to be responsible of cerebral edema in acute mountain sickness
VEGF
Main features of Monge Disease
aka chronic mountain sickness
pulmonary hypertension
cor pulmonale
secondary polycythemia
hypercarbia
Most effective preventive measure for acute mountain sickness
acclimatization by a 2- to 4-day stay at intermediate altitudes
the brain rapidly adapts to respiratory acidosis through:
the generation and secretion of bicarbonate by the choroid plexuses
the mechanism of hypercapnic pulmonary disease in inducing cerebral disorder
direct CO2 narcosis
Symptoms of hypoglycemia at
1) 30mg/dL
2) 10mg/dL
1) 30mg/dL - confusional state, seizure
2) 10mg/dL - “medullary phase”, coma, irreparable injury, dilated pupils, pale skin, shallow respiration, hypotonia, slow pulse
What is the rate of glucose utilization in the brain?
60-80mg/min
The normal brain has a glucose reserve of ______________, mostly in the form of
glycogen.
1 to 2 g (30 mmol/ 100 g of tissue)
How many moles of O2 is required for the oxidation of 1 glucose molecule
6
What happens to the 10-15% of glucose taken up by the brain if it isnt oxidized?
used for the formation of neurotransmitters, particularly GABA
Nonglucose substances that can be utilized by the brain
keto acids, lactate, pyruvate, fructose, other hexoses
The convulsions in hypoglycemia has been attributed to?
an altered integrity of neuronal membranes and to elevated NH3 and depressed GABA and lactate levels
The most common causes of hypoglycemic encephalopathy are (6):
(1) accidental or deliberate overdose of insulin or an oral diabetic agent
(2) islet cell insulin-secreting tumor of the pancreas
(3) depletion of liver glycogen, which occasionally follows a prolonged alcoholic binge, starvation, or any form of severe liver failure
(4) glycogen storage disease of infancy
(5) an idiopathic hypoglycemia in the neonatal period and infancy
(6) subacute and chronic hypoglycemia from islet cell hypertrophy and islet cell tumors of the pancreas, carcinoma of the stomach, fibrous mesothelioma, carcinoma of the cecum, and hepatoma
Ultrastructural changes in the brain seen in hypoglycemia
mitochondrial changes, first in dendrites and then in nerve cell soma, followed by nuclear membrane disruption leading to cell death
Pathogenesis of Hepatic Encephalopathy or Porto Sytemic Encephalopathy
1 abnormality of NH3 metabolism - NH3 not converted to urea because the brain does not have urea enzymes– intereferes with cerebral metabolism
2 ATP depletion - removal of NH3 depends on glutamine formation which depends on ATP dependent glutamine synthetase
3 manganese accumulation in the pallidum
4 NH3 inhibits GABA metabolism –> increased GABA
West Haven Grading of Hepatic Encephalopathy
Grade 0 - Minimal hepatic encephalopathy; lack of detectable changes in personality or behavior; minimal changes in memory, concentration, intellectual function, and coordination; asterixis is absent.
Grade 1 - Trivial lack of awareness; shortened attention span; impaired addition or subtraction; hypersomnia, insomnia, or inversion of sleep pattern; euphoria, depression, or irritability; mild confusion; slowing of ability to perform mental tasks
Grade 2 - Lethargy or apathy; disorientation; inappropriate behavior; slurred speech; obvious asterixis; drowsiness, lethargy, gross deficits in ability to perform mental tasks, obvious personality changes, inappropriate behavior, and intermittent disorientation, usually regarding time
Grade 3 - Somnolent but can be aroused; unable to perform mental tasks; disorientation about time and place; marked confusion; amnesia; occasional fits of rage; present but incomprehensible speech
Grade 4 - Coma with or without response to painful stimuli
Mainstay of treatment of hepatic encephalopathy
lactulose - inert sugar metabolized by bacteria which produces H+ covnverting ammonia to ammonium, non toxc product eliminated in the stool
Given to suppress the urease-producing organisms in the bowel
kanamycin
neomycin
Neuropathologic changes in hepatic encephalopathy
diffuse increase in the number and size of the protoplasmic astrocytes in the deep layers of the cerebral cortex, lenticular nuclei, thalamus, substantia nigra, cerebellar cortex, and red, dentate, and pontine nuclei, with little or no visible alteration in the nerve cells or other parenchymal elements
Alzheimer Type II astrocytes
a special type of nonicteric hepatic encephalopathy occuring in children and adolescents characterized by ACUTE BRAIN SWELLING in association with fatty liver
Reye Syndrome
or Reye Johnson Syndrome
Implicated pathogenesis of Reye Syndrome and aspirin toxicity
mitochondrial dysfunction
EEG finding in Reye Syndrome
diffuse arrhythmic delta activity
progressing to electrocerebral silence
True or False. The myoclonic-twitch syndrome is a component of hypertensive encephalopathy
FALSE
True or False. Cerebral edema is seen in uremic encephalopathy
FALSE
in fact neuroimaging would usually show cerebral shrinkage
True or False. All every level of the nervous system is affected in uremia
TRUE
Possible biochemical basis of uremic encephalopathy
retention of organic acids
phosphate elevation in the CSF
urea and other toxins like parathyroid hormone
Reason for the shift of water to the brain in Dialysis Disequilibrium Syndrome
water intoxication and inappropriate secretion of ADH
NOT because of reverse urea syndrome
EEG findings in Dialysis Encephalopathy (Dialysis Dementia)
invariably abnormal
paroxysmal and sometimes periodic sharp-wave or spike-and-wave activity (up to 500 mV and lasting 1 to 20 s) intermixed with abundant theta and delta activity.
The heavy metal culprit in Dialysis Dementia
Aluminum
The more severe area of microcavitation of the superficial layers of the cerebral cortex in Dialysis Dementia is found where?
left frontotemporal operculum
– explains the speech and language disturbance
True or False. Paratonia, as well as polyneuropathy, is common in Septic Encephalopathy
TRUE
Proposed pathogenesis of cerebral dysfunction in Septic Encephalopathy
altered phenylalanine metabolism and circulating cytokines
the type of hyponatremic state induced by mannitol
HYPERTONIC
SIADH causes what tyoe of hyponatremic state?
HYPOTONIC ISOVOLEMIC
the type of hyponatremic state induced by hyperglycemia
HYPERTONIC
the type of hyponatremic state induced by hyperlipidemia or hyperproteinemia
ISOTONIC
Define hyponatremia
serum Na of
Na concentration of normal saline solution
154 mEq/L
Na concentration of 3% hypertonic saline solution
513 meq/L
How to manage SIADH?
Fluid restriction per day:
if Na
Formula for Na infusion for hyponatremia
(target Na - starting Na)x0.6 x weight *kg
The brain retains its volume effectively in hypernatremia with hyperosmolarity because of the production of _____
idiogenic osmoles
possibly glucose metabolites and amino acids
How to correct hypokalemia
IV infusion of K no more than 4-6 mEq/h
Define hypercalcemia
serum Ca > 10.5mg/dL
If the serum protein content is normal, Ca levels
greater than ______ are required to produce neurologic symptoms.
12 mg/ dL
In young persons, the most common cause of hypercalcemia is
hyperparathyroidism
in older persons, the most common cause of hypercalcemia is
osteolytic bone tumors, particularly metastatic carcinoma and multiple myeloma
CPM histopathologic picture
dissolution of the sheaths of myelinated fibers and the sparing of axons
a grayish discoloration and fine granularity in
the center of the base of the pons
Extrapontine myelinolysis structures involved
internal capsule, deep cerebral white matter and corpus callosum
MRI finding of batwing lesion in the pons
CPM
How to correct hyponatremia?
no more than 10 mEq/L in the initial 24 h
and by no more than about 21 mEq/L in the initial 48 h
swollen and chromatolyzed nerve cells found in the cortical and subcortical regions (basal ganglia and thalamus) of the brains of people with Wilson disease and acquired hepatolenticular degeneration
Opalski cells
histopathologic finding in the cerebellum of hyperthermic patients
loss, pyknosis, and disintegration of Purkinje cells
gliosis throughout the cerebellar cortex
degeneration of the dentate nuclei
Vitamin deficiency that causes ataxia
E
differentiate neurologic endemic cretinism from myxedematous endemic cretinism
neurologic deafness, dysarthria, proximal limb and truncal rigid-spastic motor disorder involving mainly the legs, and mental deficiency
myxedematous - no deafness or spastic rigidity of the limbs
True or False. Thyroid hormone appears to be essential, not for neuronal formation and migration but
for dendritic-axonal development and organization
TRUE
Osmolarity of Normal saline solution
314 mOsm/L
Osmolarity of lactated ringers solution
289 mOsm/L
Blood alcohol level where in you see: Euphoria or dysphoria, shy or expansive, friendly or argumentative. Impaired concentration, judgement and sexual inhibitions
50-150mg/dL
Blood alcohol level where in you see: Slurred speech and ataxic gait, diplopia, nausea, tachycardia, drowsiness, or labile mood with sudden bursts of anger or antisocial acts
150-250 mg/dL
Blood alcohol level where in you see: Stupor alternating with combativeness or incoherent speech, heavy breathing, vomiting
300 mg/dL
Blood alcohol level where in you see: coma
400 mg/dL
Blood alcohol level where in you see: Respiratory paralysis, death
500 mg/dL
Chemicals associated with Parkinsonism
Carbon monoxide Carbon disulfide Manganese Other heavy metals Cyanide
