Renal Tubular Acidosis (RTA)

The whole terminology of renal tubular acidosis can be confusing to the newcomer. Important features to grasp are:

The acidosis refers to the plasma, not the contents of the renal tubules. Indeed, in classical (type I) renal tubular acidosis the
urine is often alkaline. Thus renal tubular acidosis is a metabolic acidosis of renal tubular origin.
There are three main types, named I, II and IV. Type III has become obsolete.

The three types have different sites of localisation in the renal tubule. However, again the terminology is confusing in that
type II is proximal, type I distal.
 

Renal tubular acidosis type I

Type I renal tubular acidosis is caused by a defect in the distal convoluted tubule which prevents the normal acidification of
the urine.
There is a failure in acid excretion.

RTA-I may be inherited or may be secondary to other renal disease.

 

Renal tubular acidosis type II

Type II renal tubular acidosis is caused by a defect in the proximal convoluted tubule which prevents the normal
reabsorption of bicarbonate ions.
RTA-II may be an isolated phenomenon or more commonly, be one of the features in patients with Fanconi's syndrome.

Renal tubular acidosis type IV

Type 4 renal tubular acidosis occurs in diseases and conditions associated with a failure of aldosterone action or
hypoaldosteronism.

In this type of renal tubular acidosis, the acidosis is a result of loss of pH regulation secondary to hyperkalaemia.
The pH of the urine is usually below 5.4, and there is hyperkalaemia, secondary to hypoaldosteronism - mineralocorticoid
deficiency causes a reduction in secretion of H+ in the distal nephron and a reduction in NH4+ sectretion. Other features
include hyperchloraemic metabolic acidosis.

Treatment is with modest doses of bicarbonate and mineralocorticoid replacement.

Bullous Pemphigoid
The bullae are formed by an immune reaction, initiated by the formation of IgGautoantibodies targeting the type XVII
collagen component of hemidesmosomes. It can also rarely involve the mucous membranes. Following antibody targeting, a
cascade of immunomodulators results in a variable surge of neutrophils, lymphocytes and eosinophils coming to the affected
area. Unclear events subsequently result in a separation along the dermal-epidermal junction and eventually stretch
bullae.Clinically the earliest lesions may appear urticarial (like hives). Tense bullae eventually erupt, most commonly at the
inner thighs and upper arms but the trunk and extremities are frequently both involved. Any part of the skin surface can be
involved. Milia are more common with epidermolysis bullosa acquisita (EBA), because of the deeper antigenic targets. A
more ring-like configuration, with a central depression or centrally collapsed bullae may indicate linear IgA disease. The
disease may be acute, but typically will wax and wane.Diagnosis is based on two biopsies of the skin, one submitted for
routine H&E staining and one for immunofluorescence studies.Treatments include Class I
topical steroids (clobetasol, halobetasol, etc.) which in some studies have proven to be equally as effective as systemic, or
pill, therapy and somewhat safer. However, in difficult to manage or widespread cases, systemicprednisone and powerful
steroid-free immunosuppressant medications such as methotrexate, azathioprine ormycophenolate mofetil may be
appropriate.
Addison's Disease 
The symptoms of Addison's disease develop insidiously, and it may take some time to be recognized. The most common
symptoms are fatigue, lightheadedness upon standing or while upright, muscle weakness, fever, weight loss, difficulty in
standing up, anxiety, nausea, vomiting, diarrhea, headache, sweating, changes in mood and personality, joint and muscle
pains. Some have marked cravings for salt or salty foods due to the urinary losses of sodium.[Affected individuals may note
increased tanning since adrenal insufficiency is manifested in the skin primarily by hyperpigmentation. On examination, the
following may be noticed:* Low blood pressure that falls further when standing (orthostatic hypotension) * In long-standing
Addison's Disease, the pinna of the ear may become calcified * Most people with primary Addison's have darkening
(hyperpigmentation) of the skin, including areas not exposed to the sun; characteristic sites are skin creases (e.g. of the
hands), nipple, and the inside of the cheek (buccal mucosa), also old scars may darken. This occurs because melanocyte-
stimulating hormone (MSH) and adrenocorticotropic hormone (ACTH) share the same precursor molecule, Pro-
opiomelanocortin (POMC). After production in anterior pituitary gland, POMC gets cleaved into Gamma-MSH, ACTH and
Beta-lipotropin. The subunit ACTH undergoes further cleavage to produce Alpha-MSH, the most important MSH for skin
pigmentation. In secondary and tertiary forms of Addison's, skin darkening does not occur. * Medical conditions such as type
I diabetes, autoimmune thyroid disease (Hashimoto's thyroiditis and goiter) and vitiligo often occur together with Addison's
(often in the setting of Autoimmune polyendocrine syndrome). Hence, symptoms and signs of any of the former conditions
may also be present in the individual with Addison's. The occurrence of Addison's Disease in someone who also has
Hashimoto's thyroiditis is called Schmidt syndrome. An "Addisonian crisis" or "adrenal crisis" is a constellation of symptoms
that indicate severe adrenal insufficiency. This may be the result of either previously undiagnosed Addison's disease, a
disease process suddenly affecting adrenal function (such as adrenal hemorrhage), or an intercurrent problem (e.g.
infection, trauma) in someone known to have Addison's disease. It is a medical emergency and potentially life-threatening
situation requiring immediate emergency treatment. Characteristic symptoms are: * Sudden penetrating pain in the
legs, lower back or abdomen * Severe vomiting and diarrhea, resulting in dehydration * Low blood pressure * Syncope (loss
of consciousness and ability to stand) * Hypoglycemia * Confusion, psychosis, slurred speech * Severe lethargy *
Hyperkalemia * Hypercalcemia * Convulsions * Fever

The following are associated with neonatal hypoglycaemia,

FFTTT
Causes of neonatal hypoglycaemia can be classified as follows: 
1. Hyperinsulinism (maternal diabetes - islet cell hyperplasia - Beckwith-Wiedemann 
syndrome Nesidioblastosis - islet cell adenoma). 
2. Decreased production (prematurity - ntrauterine growth retardation - glycogen 
storage disease glactosaemia). 
3. Increased utilization (hypothermia – polycythaemia – asphyxia – sepsis). 
4. Inborn errors (maple syrup urine disease (MSUD), - proprionic acidaemia, - 
tyrosinaemia). 
5. Endocrine causes (panhypopituitarism, - adrenal insufficiency). 
6. Miscellaneous (maternal drugs (beta agonists/blockers, thiazides), - post-exchange 
transfusion

Lateral Medullary Syndrome / Wallenberg Syndrome / PICA Syndrome

This syndrome is characterized by sensory deficits affecting the trunk (torso) and extremities on the opposite side of the
infarction and sensory deficits affecting the face and cranial nerves on the same side with the infarct. Specifically, there is a
loss of pain and temperature sensation on the contralateral (opposite) side of the body and ipsilateral (same) side of the
face. This crossed finding is diagnostic for the syndrome. Clinical symptoms include difficulty swallowing, or
dysphagia,slurred speech, ataxia, facial pain, vertigo, nystagmus, Horner syndrome, diplopia, and possibly palatal
myoclonus. Affected persons have difficulty in swallowing (dysphagia) resulting from involvement of the nucleus ambiguus,
as well as slurred speech (dysarthria)and disordered vocal quality ( dysphonia ) . Damage to the spinal trigeminal
nucleus causes absence of pain on the ipsilateral side of the face, as well as an absent corneal reflex. The spinothalamic
tract is damaged, resulting in loss of pain and temperature sensation to the opposite side of the body. The damage to the
cerebellum or the inferior cerebellar peduncle can cause ataxia. Damage to the hypothalamospinal fibers disrupts
sympathetic nervous system relay and gives symptoms analogous to Horner syndrome. Nystagmus and vertigo, which may
result in falling, caused from involvement of the region of Deiters' nucleus and other vestibular nuclei. Onset is usually acute
with severe vertigo. Palatal myoclonus may be observed due to disruption of the central tegmental tract.

Carbonic anhydrase (CA) isoenzyme II deficiency—

formerly called the syndrome of osteopetrosis with renal tubular acidosis and cerebral calcification--is an autosomal recessive
"inborn error of metabolism" that has disclosed important insight concerning osteoclast function. Nearly 50 cases have been
described, predominantly from the Middle East and Mediterranean region. It is discovered late in infancy or early in childhood
through developmental delay, short stature, fracture, weakness, cranial nerve compression, dental malocclusion, and/or mental
subnormality. Typical radiographic features of osteopetrosis are present, and histopathologic study of the iliac crest reveals
unresorbed calcified primary spongiosa. The radiographic findings are unusual, however, in that cerebral calcification appears by
early childhood and the osteosclerosis and skeletal modeling defects may gradually resolve by adulthood. Patients are usually not
anemic. A hyperchloremic metabolic acidosis, sometimes with hypokalemia, is caused by renal tubular acidosis that may be a
proximal, distal, or combined type. Several different mutations within the CA II gene have been identified. There is no established
medical therapy, and the long-term outcome remains to be characterized. Prenatal diagnosis has not been reported. Delineation of
CA II deficiency establishes an important role in humans for CA II. The pathogenesis of the mental subnormality and cerebral
calcification is poorly understood; however, CA II deficiency provides significant insight concerning CA II in renal regulation of
acid/base homeostasis and osteoclast-mediated bone resorption.

Wounds:
Open wounds can be classified according to the object that caused the wound. The types of open wound are:

    * Incisions or incised wounds, caused by a clean, sharp-edged object such as a knife, a razor or a glass splinter.
    * Lacerations, irregular tear-like wounds caused by some blunt trauma. The term laceration is commonlymisused in
reference to incisions.
    * Abrasions (grazes), superficial wounds in which the topmost layer of the skin (the epidermis) is scraped off. Abrasions
are often caused by a sliding fall onto a rough surface.
    * Puncture wounds, caused by an object puncturing the skin, such as a nail or needle.
    * Penetration wounds, caused by an object such as a knife entering and coming out from the skin .
    * Gunshot wounds, caused by a bullet or similar projectile driving into or through the body. There may be two wounds,
one at the site of entry and one at the site of exit, generally referred to as a "through-and-through."

Closed wounds have fewer categories, but are just as dangerous as open wounds. The types of closed wounds are:

    * Contusions, more commonly known as bruises, caused by a blunt force trauma that damages tissue under the skin.
    * Hematomas, also called a blood tumor, caused by damage to a blood vessel that in turn causes blood to collect under
the skin.
    * Crush injury, caused by a great or extreme amount of force applied over a long period of time.
    * Chronic and Acute Acute or traumatic wounds are the result of injuries that disrupt the tissue. Chronic wounds are those
that are caused by a relatively slow process that leads to tissue damage. Chronic wounds include pressure, venous,
and diabetic ulcers. Typically, an insufficiency in the circulation or other systemic support of the tissue causes it to fail and
disintegrate. Infection then takes hold of the site and becomes a chronic abscess. Once the infection hits a critical point, it
can spread locally or become systemic (sepsis).

Lumbar puncture:
In medicine, a lumbar puncture (colloquially known as a spinal tap) is a diagnostic and at times therapeuticprocedure that is
performed in order to collect a sample of cerebrospinal fluid (CSF) for biochemical, microbiological, and cytological  analysis,
or very rarely as a treatment ("therapeutic lumbar puncture") to relieve increased intracranial pressure. The fictional band
Spinal Tap, from the 1984 film This Is Spinal Tap, was named after the procedure.

The most common purpose for a lumbar puncture is to collect cerebrospinal fluid in a case of suspectedmeningitis, since
there is no other reliable tool with which meningitis, a life-threatening but highly treatable condition, can be excluded. Young
infants commonly require lumbar puncture as a part of the routine workup for fever without a source, as they have a much
higher risk of meningitis than older persons and do not reliably show signs of meningeal irritation (meningismus). In any age
group, subarachnoid hemorrhage, hydrocephalus, benign intracranial hypertension and many other diagnoses may be
supported or excluded with this test.

Lumbar punctures may also be done to inject medications into the cerebrospinal fluid ("intrathecally"), particularly for spinal
anesthesia or chemotherapy. It may also be used to detect the presence of malignant cells in the CSF, as in
carcinomatous meningitis or medulloblastoma. Lumbar punctures can be unpleasant for some people, due to increased
sensitivity when the needle is inserted to collect the cerebrospinal fluid.

Lumbar puncture should not be performed when idiopathic (unidentified cause) increased intracranial pressure  (ICP) is
present. The exception is therapeutic use of lumbar puncture to relieve ICP. Whether or not CT brain scan should be
performed prior to LP remains controversial. If the patient is over 65, has a reduced GCS, has seizure activity or focal
neurological signs, consideration should be given to CT.Ophthalmoscopy for papilledema should also be performed prior to
any LP to check for raised ICP. Also, lumbar puncture should not be attempted when there is coagulopathy, abnormal
respiratory pattern,hypertension with bradycardia and deteriorating consciousness or when there are decreased levels of
platelets in the blood (less than 50 x 109/L). Lumbar puncture in cases of vertebral deformities (scoliosis or kyphosis) is also
contraindicated in hands of an unexperienced physician or physician assistant.

In performing a lumbar puncture, first the patient is usually placed in a left (or right) lateral position with his/her neck bent in
full flexion and knees bent in full flexion up to his/her chest, approximating a fetal position  as much as possible. It is also
possible to have the patient sit on a stool and bend his/her head and shoulders forward. The area around the lower back is
prepared using aseptic technique. Once the appropriate location is palpated, local anaesthetic is infiltrated under the skin
and then injected along the intended path of the spinal needle. A spinal needle is inserted between the lumbar vertebrae
L3/L4 or L4/L5 and pushed in until there is a "give" that indicates the needle is past the dura mater. The needle is again
pushed until there is a second 'give' that indicates the needle is now past the arachnoid mater, and in the subarachnoid
space. The stylet from the spinal needle is then withdrawn and drops of cerebrospinal fluid are collected. The
opening pressure of the cerebrospinal fluid may be taken during this collection by using a simple column manometer.
The procedure is ended by withdrawing the needle while placing pressure on the puncture site. In the past, the patient would
often be asked to lie on his/her back for at least six hours and be monitored for signs of neurological problems, though there
is no scientific evidence that this provides any benefit. The technique described is almost identical to that used in spinal
anesthesia, except that spinal anesthesia is more often done with the patient in a sitting position.

The upright seated position is advantageous in that there is less distortion of spinal anatomy which allows for easier
withdrawal of fluid. It is preferred by some practitioners when a lumbar puncture is performed on an obese patient where
having them lie on their side would cause a scoliosis and unreliable anatomical landmarks. On the other hand, opening
pressures are notoriously unreliable when measured on a seated patient and therefore the left or right lateral (lying down)
position is preferred if an opening pressure needs to be measured.

Patient anxiety during the procedure can lead to increased CSF pressure, especially if the person holds their breath, tenses
their muscles or flexes their knees too tightly against their chest. Diagnostic analysis of changes in fluid pressure during
lumbar puncture procedures requires attention both to the patient's condition during the procedure and to their medical
history.

Explanation: 
Loose-jointedness is often striking in patients with the Marfan syndrome. Flat feet (pes planus),
hyperextensibility at the knees (genu recurvatum), elbows, and fingers, congenital dislocation of
the hips, and recurrent dislocation of the patellae are manifestations of laxity of ligaments and
joint capsules. A relatively narrow palm of the hand, long thumb, and longitudinal laxity of the
hand are the bases for the Steinberg thumb sign: the thumb apposed across the palm extends
well beyond the ulnar margin of the hand. Depression of the sternum (pectus excavatum),
protrusion, or an asymmetric combination often results. The vertebral column is frequently
deformed. The normal thoracic kyphos is often reduced, resulting in a 'straight back' or an
outright thoracic lordosis. Scoliosis may involve multiple segments and may progress rapidly,
particularly during the adolescent growth spurt. Most patients with the Marfan syndrome have
myopia and about one-half have subluxation of the lenses (ectopia lentis). The ascending aorta
bears the main stress of ventricular ejection, leading to progressive dilatation beginning in the
sinuses of Valsalva. Aortic regurgitation and dissection are the main causes of death.

Answer :USMLE step 2 Mcq 362:A patient with symptomatic WPW

syndrome undergoes an intracardiac electrophysiological Study
Correct Answer: A
Explanation: 
The exact nature of the prexcitation syndrome is assessed. Most of the WPW syndrome are
related to a atrioventricular accessory connection or Kent bundle : the degree of prexcitation
increases during premature atrial stimulation until the refractory period of accessory pathway is
reached, because the conduction time does not change in accessory pathway with the shortening
of atrial cycle length while it increases in the AV node.   Rarely the WPW syndrome is related to a
nodoventricular accessory pathway or Mahaim bundle and the degree of preexcitation remains
unchanged during premature atrial stimulation.   The accessory pathway refractory period
depends on the driven cycle length. Refractory period of the accessory pathway decreases as the
driven cycle length shortens..   Beta adrenergic stimulation results in shortening of the
anterograde refractory period of the accessory pathway and an increase in ventricular rates
during atrial pacing and atrial fibrillation.   Isoproterenol test was also previously used to verify
the efficacy of antiarrhythmic drug before the era of catheter ablation of accessory pathway. The
loss of efficacy of some antiarrhythmic drugs was demonstrated after isoproterenol
administration.   Atrial fibrillation is easily induced during intracardiac studies by salvos of rapid
atrial stimulation and is not specific. The induction of an atrial fibrillation by intracardiac
programmed stimulation is obtainedin 45% in asymptomatic patients and in 75 % of patients
with only documented reentrant tachycardia, atrial fibrillation is induced in 95 % of those with
documented atrial fibrillation. The important variations of the incidence of induced atrial
fibrillation depends on the technique of programmed stimulation, on the interpretation of the
duration of induced arrhythmia and on the use of isoproterenol infusion or other means to
reproduce the effects of adrenergic stimulation. <br> The induction of an atrial fibrillation during
transesophageal pacing has a best clinical significance :The incidence of inductionof atrial
fibrillation also depends on the presence of an associated heart disease and the age of the
patient : the induction of atrial fibrillation is rarely noted in children younger than 10 years, is
induced in 20 % of teenagers and adults without heart disease and becomes relatively frequent
in elderly   - Ventricular tachyarrhythmias also are easily induced in asymptomatic or
symptomatic patients by programmed ventricular stimulation and are not specific in patients with
WPW syndrome : the induction of a ventricular fibrillation is noted in 4 % of WPW syndrome and
theinduction of nonsustained multiform ventricular tachycardia in 37 % of them.   - Antidromic
tachycardia which is a reciprocating tachycardia using the accessory pathway for the anterograde
conduction and the normal AV conduction system for retrograde conduction, is a rare finding
(5%), more frequently noted in young patients with a good retrograde normal VA conduction or
in patients with several accessory pathways and seems more frequent in patients at risk of rapid
arrhythmias. <br> - Orthodromic tachycardia which is a reciprocating tachycardia using the
normal AV conduction system for the anterograde conduction and the accessory pathway for the
retrograde conduction, is rarely induced in asymptomatic patients (< 10%) , but represents the
most frequent tachycardia of symptomatic patients complaining tachycardia and palpitations (90
%).

828 questions to master before usmle

Questions
1. Which of the following features supports a diagnosis of carditis in a child suspected
of having rheumatic fever? 

A Pan-systolic murmur in the mitral area.

B Elevated sleeping pulse. 
C Sinus arrhythmia. 
D Ejection systolic murmur at the left sternal border. 
E Pericardial rub.
2. Respiration is stimulated by the following: 

A Hypercarbia. 
B Hypoxia. 
C Acidosis. 
D Increased barometric pressure. 
E Carbon monoxide inhalation.
3. Early cardiac failure during the neonatal period is often associated with: 

A Peripheral oedema 
B Failure to thrive 
C Feeding difficulties 
D Episodes of apnoea 
E A raised pulse rate but normal respiratory rate