Week 8 Flashcards
thrombotic thrombocytopenic purpura and idiopathic thrombocytopenic purpura
Generally, these disorders are called thrombocytopenic purpura, a condition where platelet counts are affected resulting in the appearance of red or purple discolorations on the skin.
ITP and TTP are both blood disorders that involve platelet counts.
In ITP, there is a failure of the blood to clot, while TTP results from the formation of too many blood clots which lead to overused platelets.
Though each condition has a specific mechanism, both have the same end symptoms, which are easy bruising and bleeding.
Treatment of TTP involves blood replacement therapy to correct the imbalance of the blood components, while ITP can be treated with oral steroids.
The cause for ITP cannot be determined, while TTP is usually caused by spontaneous platelet aggregation.
ITP symptoms:
Skin that bruises very easily and even spontaneously
– A rash consisting of small red dots (petechiae) that represent small haemorrhages caused by broken blood vessels or leaks in a capillary wall
– Bleeding from the gums
– Frequent and long-lasting nose bleeds that are hard to stop
– Blood blisters on the inside of cheeks
– Excessive and prolonged menstrual bleeding
– Less likely, signs of internal bleeding, with blood in urine, vomit, or bowel movements
-in rare patients, bleeding in the brain called intracranial haemorrhage that is very much like a stroke
-Debilitating fatigue, depression, low mental and physical energy
TTP symptoms: large bruises, fever, weakness, shortness of breath, confusion, Changes in mental status Thrombocytopenia Reduced kidney function Haemolytic anaemia Headaches Hypertension
Huntington’s Disease
The mean age at onset of symptoms is 30-50 years.
In some cases symptoms start before the age of 20 years with behavioural disturbances and learning difficulties at school - juvenile Huntington’s disease (JHD); this is more common when the condition has been inherited from the father.
Early signs may be personality change, self-neglect, apathy with clumsiness, fidgeting with fleeting facial grimaces.
Behavioural problems may lead to family conflict, marital breakdown and job loss before a formal diagnosis has been made.
Depressed mood is significantly higher in HD
HD then leads to progressive chorea, rigidity and dementia. It is frequently associated with seizures.
Chorea is initially mild but may be severe and cause uncontrollable limb movements.
As the disease progresses, chorea is gradually replaced by dystonia and Parkinsonian features.
Dysarthria, dysphagia and abnormal eye movements are common. There may also be other movement disorders - eg, tics and myoclonus.
HD patients can develop a wide array of dysfunction, including HD-related cardiomyopathy and skeletal muscle wasting.
Dystonia is a movement disorder in which involuntary sustained or intermittent muscle contractions cause twisting and repetitive movements, abnormal postures, or both. Chorea is an ongoing random-appearing sequence of one or more discrete involuntary movements or movement fragments.
Chorea:
Benzodiazepines, valproic acid, dopamine-depleting agents (eg, tetrabenazine) and neuroleptics may be useful
Depression:
Selective serotonin reuptake inhibitors (SSRIs) are first-choice antidepressants. Refractory depression may require ECT treatment
Death is usually from an intercurrent illness - eg, pneumonia.
Suicide is the second most common cause of death
Anencephaly
ANENCEPHALY is a neural tube defect that occurs when the cephalic (head) end of the neural tube fails to close, usually between the 23rd and 26th days of pregnancy, resulting in the absence of a major portion of the brain, skull, and scalp. Infants with this disorder are born without a forebrain - the largest part of the brain consisting mainly of the cerebrum, which is responsible for thinking and coordination. The remaining brain tissue is often exposed - not covered by bone or skin.
Infants born with anencephaly are usually blind, deaf, unconscious, and unable to feel pain. Although some individuals with anencephaly may be born with a rudimentary brainstem, the lack of a functioning cerebrum permanently rules out the possibility of ever gaining consciousness.
Colpocephaly
abnormal enlargement of the occipital horns - the posterior or rear portion of the lateral ventricles (cavities or chambers) of the brain. This enlargement occurs when there is an underdevelopment or lack of thickening of the white matter in the posterior cerebrum. Colpocephaly is characterized by microcephaly (abnormally small head) and delayed development. Other features may include motor abnormalities, muscle spasms, and seizures.
occurs between the second and sixth months of pregnancy. Colpocephaly may be diagnosed late in pregnancy, although it is often misdiagnosed as hydrocephalus. Anticonvulsant medications can be given to prevent seizures, and doctors try to prevent contractures (shrinkage or shortening of muscles).
Holoprosencephaly
A failure of the prosencephalon (the forebrain of the embryo) to develop. During normal development the forebrain is formed and the face begins to develop in the fifth and sixth weeks of pregnancy. Holoprosencephaly is caused by a failure of the embryo’s forebrain to divide to form bilateral cerebral hemispheres.
The most severe of the facial defects (or anomalies) is cyclopia, an abnormality characterized by the development of a single eye, located in the area normally occupied by the root of the nose, and a missing nose or a nose in the form of a proboscis (a tubular appendage) located above the eye. Cebocephaly, another facial anomaly, is characterized by a small, flattened nose with a single nostril situated below incomplete or underdeveloped closely set eyes. Patau’s syndrome (trisomy 13) and Edwards’ syndrome (trisomy 18) have been found in association with holoprosencephaly
The least severe in the spectrum of facial anomalies is the median cleft lip.
Lissencephaly
is a rare brain malformation characterized by microcephaly and the lack of normal convolutions (folds) in the brain. It is caused by defective neuronal migration, the process in which nerve cells move from their place of origin to their permanent location. Symptoms of the disorder may include unusual facial appearance, difficulty swallowing, failure to thrive, and severe psychomotor retardation. Anomalies of the hands, fingers, or toes, muscle spasms, and seizures may also occur.
Tay Sachs disease
Tay-Sachs disease is a rare, neurodegenerative disorder in which deficiency of an enzyme (hexosaminidase A) results in excessive accumulation of certain fats (lipids) known as gangliosides in the brain and nerve cells.
The most common form of Tay-Sachs disease is the Infantile form, which can present around 6 months of age as reduced vision and an exaggerated startle response and eventually progress to a gradual loss of skills and seizures by age 2 and early death, usually by the age of 5. There is also a juvenile version of the disease beginning at about the age of 5 years of age and adult forms of Tay-Sachs disease also known as late-onset Tay Sachs disease (LOTS) beginning in the late teens and beyond. All three forms of Tay-Sachs disease are inherited in an autosomal recessive manner and the age of onset is a function of the amount, if any, of residual enzyme activity.
Infants may appear completely unaffected at birth. Initial symptoms, which usually develop between 3 and 6 months, can include mild muscle weakness, twitching or jerking of muscles (myoclonic jerks) and an exaggerated startle response, such as when there is a sudden or unexpected noise. The startle response may be partly due to an increased sensitivity to sound (acoustic hypersensitivity).
Between six and 10 months, affected infants may fail to gain new motor skills. They may no longer make eye contact and there may be unusual eye movements. They may be listlessness and irritable. As affected infants age, they may experience slow growth, progressive muscle weakness and diminished muscle tone (hypotonia). Affected infants may also exhibit gradual loss of vision, involuntary muscle spasms (myoclonus), slow, stiff movements (spasticity) and the loss of previously acquired skills (i.e., psychomotor regression) such as crawling or sitting up.
A characteristic symptom of Tay-Sachs disease is the development of a macular “cherry red” spot.
Gaucher Disease
Gaucher disease is a rare, inherited metabolic disorder in which deficiency of the enzyme glucocerebrosidase results in the accumulation of harmful quantities of certain fats (lipids), specifically the glycolipid glucocerebroside, throughout the body especially within the bone marrow, spleen and liver.
Gaucher disease type 1 is also known as non-neuronopathic, because it does not involve the central nervous system (brain and spinal cord). Type 1 Gaucher disease is the most common form of the condition. Most individuals with Gaucher disease type 1 experience easy bruising due to low levels of blood clotting cells known as platelets (thrombocytopenia), chronic fatigue due to low levels of circulating red blood cells (anemia), and an abnormally enlarged liver and/or spleen (hepatosplenomegaly). Affected individuals may also experience lack of blood supply (infarction) to various bones of the body resulting in dull or intense bone pain (bone crises), degeneration (avascular necrosis) and deformity of affected bones, and thinning and weakening of bones (osteoporosis). Such skeletal abnormalities result in an increased susceptibility to fractures. In rare cases, affected individuals may also experience involvement of the lungs and/or kidneys.
Gaucher disease type 2, also known as acute neuronopathic Gaucher disease, occurs in newborns and infants and is characterized by neurological complications due to the abnormal accumulation of glucocerebroside in the brain. Enlargement of the spleen (splenomegaly) is often the first symptom and may become apparent before six months of age. Enlargement of the liver (hepatomegaly) is not always evident. Affected infants may lose previously acquired motor skills and exhibit low muscle tone (hypotonia), involuntary muscle spasms (spasticity) that result in slow, stiff movements of the arms and legs, and crossed eyes (strabismus). In addition, affected infants may experience difficulty swallowing (dysphagia), which may result in feeding difficulties; abnormal positioning or bending of the neck (retroflexion); and failure to gain weight and grow at the expected rate (failure to thrive) and high-pitched breathing (stridor) due to contraction of the muscles of the voice box (laryngeal spasm). Anemia and thrombocytopenia may also occur. Gaucher disease type 2 often progresses to life-threatening complications such as respiratory distress or the entrance of food into the respiratory passages (aspiration pneumonia). Severely affected newborns may show skin abnormalities (collodion skin or ichthvosiform changes) and generalized swelling (hydrops), with death in the first few weeks of life. Other children with Gaucher disease type 2 have greatly reduced lifespans, with death usually occurring between 1 and 3 years of life.
Gaucher disease type 3, also known as chronic neuronopathic Gaucher disease, occurs during the first decade of life. In addition to the blood and bone abnormalities discussed above, affected individuals develop neurological complications that develop and progress slower than in Gaucher disease type 2. Associated neurological complications include mental deterioration; an inability to coordinate voluntary movements (ataxia); and brief, shock-like muscle spasms of the arms, legs or entire body (myoclonic seizures). Some individuals with Gaucher disease type 3 may have difficulty moving their eyes from side-to-side (horizontal gaze palsy). Patients with Type 3 Gaucher disease can also have a vertical gaze palsy that usually occurs later than the horizontal gaze paresis. A significant proportion of patients also develop pulmonary (lung) disease (interstitial lung disease). There can be wide variability in presentation and clinical course among patients with type 3 Gaucher disease.
There are current FDA-approved drug therapy options that include enzyme replacement therapy (ERT) and substrate reduction therapy (SRT).
Niemann-Pick Disease
Niemann-Pick disease types A and B occur when the body lacks enzymes needed to break down sphingomyelin.
Niemann-Pick disease type C occurs when the body is not able to break down cholesterol and other lipids.
The most severe forms tend to occur in Ashkenazi Jewish people. The milder forms occur in all ethnic groups.
Children with type A (the most severe form) fail to grow normally and have several neurologic problems. These children usually die by age 2 or 3.
Children with type B develop fatty growths in the skin, areas of dark pigmentation, and an enlarged liver, spleen, and lymph nodes. They may be intellectually disabled.
Children with type C develop symptoms during childhood, with seizures and neurologic deterioration. Type C is always fatal, and most children die before age 20.
Possible bone marrow transplantation, stem cell transplantation, and enzyme replacement
None of the types of Niemann-Pick disease can be cured, and children tend to die of infection or progressive dysfunction of the central nervous system (the brain and spinal cord).
Hurler syndrome
Hurler syndrome is the most severe form of mucopolysaccharidosis type 1 (MPS1; see this term), a rare lysosomal storage disease, characterized by skeletal abnormalities, cognitive impairment, heart disease, respiratory problems, enlarged liver and spleen, characteristic facies and reduced life expectancy.
Patients present within the first year of life with musculoskeletal alterations including short stature, dysostosis multiplex, thoracic-lumbar kyphosis, progressive coarsening of the facial features (including large head with bulging frontal bones, depressed nasal bridge with broad nasal tip and anteverted nostrils, full cheeks and enlarged lips), cardiomyopathy and valvular abnormalities, neurosensorial hearing loss, enlarged tonsils and adenoids, and nasal secretion. Developmental delay is usually observed between 12 and 24 months of life and is primarily in the realm of speech with progressive cognitive and sensorial deterioration. Hydrocephaly can occur after the age of two. Diffuse corneal compromise leading to corneal opacity becomes detectable from three years of age onwards. Other manifestations include organomegaly, hernias and hirsutism.
Hematopoietic stem cell transplantation (HSCT) is the treatment of choice for patients with Hurler syndrome under 2.5 years of age (and in selected patients over this age limit) as it can prolong survival, preserve neurocognition, and ameliorate some somatic features. HSCT should be performed early in the disease course, before developmental deterioration begins. Enzyme replacement therapy (ERT) with laronidase is recommended for all Hurler patients and is a lifelong therapy which alleviates non neurological symptoms.
anticholinergics
Antipsychotics (haloperidol, olanzapine, rispiridone)
Anxiolytics (diazepam etc)
Antidepressants
CVS and antihypertensives (digoxin, nifedipine, furosemide, captopril)
Ranitidine and ipratropium bromide
Sarcoiodosis
Granulomas form in lungs, skin, lymph nodes or other.
General symptoms: fatigue, weight loss, joint aches and pains (which occur in about 70% of cases), arthritis, dry eyes, swelling of the knees, blurry vision, shortness of breath, a dry, hacking cough, or skin lesions
Lungs: wheezing, cough, shortness of breath, chest pain
Skin: lumps, ulcers, discoloured skin
Children: weight loss, bone pain, feeling tired
Usual onset is 20–50 and more common in women
Duration of a few years to long term.
Histologically, sarcoidosis of the heart is an active granulomatous inflammation surrounded by reactive oedema. The distribution of affected areas is patchy with localised enlargement of heart muscles. This causes scarring and remodelling of the heart, which leads to dilatation of heart cavities and thinning of heart muscles. As the situation progresses, it leads to aneurysm of heart chambers. When the distribution is diffuse, there would be dilatation of both ventricles of the heart, causing heart failure and arrhythmia. When the conduction system in the intraventricular septum is affected, it would lead to heart block, ventricular tachycardia and ventricular arrhythmia, causing sudden death.
Manifestations in the eye include uveitis, uveoparotitis, and retinal inflammation, which may result in loss of visual acuity or blindness.
Ibuprofen, prednisone, methotrexate
Amyloidosis
Amyloid fibrils build up in tissues.
fatigue, peripheral oedema, weight loss, shortness of breath, palpitations, and feeling faint with standing.
Amyloid deposition in the kidney often involve the glomerular capillaries and mesangial regions, affecting the organ’s ability to filter and excrete waste and retain plasma protein. This can lead to high levels of protein in the urine (proteinuria) and nephrotic syndrome.
Amyloid deposition in the heart can cause both diastolic and systolic heart failure. EKG changes may be present, showing low voltage and conduction abnormalities like atrioventricular block or sinus node dysfunction.
Amyloid proteins deposit most commonly inside the knee, followed by hands, wrists, elbow, hip, and ankle, causing joint pain.
IgA nephropathy
The classic presentation for the non-aggressive form (in 40–50% of the cases) is episodic haematuria, which usually starts within a day or two of a non-specific upper respiratory tract infection (hence synpharyngitic), as opposed to post-streptococcal glomerulonephritis, which occurs some time (weeks) after initial infection.
IgA nephropathy has a very variable course, ranging from a benign recurrent haematuria up to a rapid progression to chronic kidney failure and failure of other major organs. Also, IgA nephropathy recurs in transplants despite the use of ciclosporin, azathioprine or mycophenolate mofetil, cyclophosphamide, Isotretinoin and steroids in these patients.
Thiamine deficiency
Thiamine deficiency is a medical condition of low levels of thiamine (vitamin B1). Severe and chronic = beriberi.
Dry beriberi causes wasting and partial paralysis resulting from damaged peripheral nerves. It is also referred to as endemic neuritis. It is characterized by:
Difficulty with walking Tingling or loss of sensation (numbness) in hands and feet Loss of tendon reflexes Loss of muscle function or paralysis of the lower legs Mental confusion/speech difficulties Pain Involuntary eye movements (nystagmus) Vomiting
Wet beriberi affects the heart and circulatory system. It is sometimes fatal, as it causes a combination of heart failure and weakening of the capillary walls, which causes the peripheral tissues to become oedematous. Wet beriberi is characterized by:
Increased heart rate Vasodilation leading to decreased systemic vascular resistance, and high-output heart failure Elevated jugular venous pressure Dyspnoea on exertion Paroxysmal nocturnal dyspnoea Peripheral oedema and generalized oedema Dilated cardiomyopathy
Gastrointestinal beriberi causes abdominal pain. It is characterized by:
Abdominal pain
Nausea
Vomiting
Lactic acidosis
Many people with beriberi can be treated with thiamine alone, IV then oral.
Pagets bone disease
Paget’s disease of bone is a chronic disease of the skeleton. In healthy bone, a process called remodeling removes old pieces of bone and replaces them with new, fresh bone. Paget’s disease causes this process to shift out of balance, resulting in new bone that is abnormally shaped, weak, and brittle. Paget’s disease most often affects older people, occurring in approximately 2 to 3 percent of the population over the age of 55.
Many patients with Paget’s disease have no symptoms at all and are unaware they have the disease until x-rays are taken for some other reason. When bone pain and other symptoms are present, they can be related to the disease itself or to complications that arise from the disease—such as arthritis, bone deformity, and fractures.
