Paracetamol poisoning

Acetaminophen poisoning

The minimum dose that causes toxicity :  In single dose – 150mg/kg  or 10gm for adult & 200mg/kg for children

Clinical features

Phase I : 30 minutes – 24 hours after ingestion

The patient may be asymptomatic or may present with anorexia, nausea, vomiting, malaise

Physical examination may reveal pallor & diaphoresis

Phase II : 18 - 72 hours after ingestion

Right upper quadrant abdominal pain , anorexia, nausea, vomiting & decreased urinary output

Physical examination may reveal upper right quadrant tenderness, tachycardia & hypotension

Phase III : 72 – 96 hours after ingestion

Also known as hepatic phase

Characterized by nausea, vomiting, abdominal pain, tender hepatic edge on palpation, jaundice, hypoglycemia, coagulopathy, hepatic encephalopathy & acute renal failure.

Death may occur due to multiorgan failure

Phase IV : 4 days – 3 weeks after ingestion

 Also known as recovery phase

Complete resolution of symptoms & recovery of organs takes place

Investigations

Plasma acetaminophen levels are measured . the values are plotted on the Rumack Matthew nomogram to determine the risk of hepatotoxicity

Liver function tests

Renal fucnction tests

PT & INR

ECG done to rule out congestion of cardioactive susbstances

Arterial blood gas – pH < 7.3 indicates poor outcome

Serum amylase & lipase levels to rule out pancreatic injury

If encephalopathy is present, CT brain is done to look for cerebral edema & arterial serum ammonia levels are obtained

Treatment

 The acute management consists of stabilizing airway, breathing & circulation & administration of the antidote- N-acetyl-Cysteine, if indicated

Indications of N-acetyl-Cysteine

Plasma acetaminophen levels above the lower line in the Rumack Matthew nomogram

Suspected ingestion ˃ 7.5gm in a single dose

Patients presenting late with laboratory evidence of liver injury & h/o acetaminophen ingestion

Patients with unknown time of ingestion with serum concentration ˃10mcg

Autosomal Recessive

Autosomal recessive

In autosomal recessive inheritance

·         only homozygotes are affected

·         males and females are equally likely to be affected

·         not manifest in every generation - may 'skip a generation'

If two heterozygote parents

·         25% chance of having an affected (homozygote) child

·         50% chance of having a carrier (heterozygote) child

·         25% chance of having an unaffected (i.e. genotypical) child

If one affected parent (i.e. homozygote for gene) and one unaffected (i.e. not a carrier or affected)

·         all the children will be carriers

Autosomal recessive disorders are often metabolic in nature and are generally more life-threatening compared to autosomal dominant conditions

Autosomal recessive conditions

Autosomal recessive conditions are often thought to be 'metabolic' as opposed to autosomal dominant conditions being 'structural', notable exceptions:

·         some 'metabolic' conditions such as Hunter's and G6PD are X-linked recessive whilst others such as hyperlipidaemia type II and hypokalaemic periodic paralysis are autosomal dominant

·         some 'structural' conditions such as ataxia telangiectasia and Friedreich's ataxia are autosomal recessive

The following conditions are autosomal recessive:

·                     Albinism

·                     Ataxia telangiectasia

·                     Congenital adrenal hyperplasia

·                     Cystic fibrosis

·                     Cystinuria

·                     Familial Mediterranean Fever

·                     Fanconi anaemia

·                     Friedreich's ataxia

·                     Glycogen storage disease

·                     Haemochromatosis

·                     Homocystinuria

·                     Lipid storage disease: Tay-Sach's, Gaucher, Niemann-Pick

·                     Mucopolysaccharidoses: Hurler's

·                     PKU

·                     Sickle cell anaemia

·                     Thalassaemias

·                     Wilson's disease

Tunnel vision

Tunnel vision is the concentric diminution of the visual fields

Causes :

• Papilloedema
• Glaucoma
• Retinitis Pigmentosa
• Choroidoretinitis
• Hysteria
• Optic atrophy secondary to tabes dorsalis

Poisoning & Antidotes

Poisoning	Treatment
Atropine	Physostigmine
Acetaminophen / Paracetamol	N-acetyl cysteine
Ergot alkaloids	Nitroprusside
β-blockers	Glucagon & calcium
Organophosphorous compounds	Atropine
Carbamates	Atropine
Benzodiazepines	Flumazenil
Zolpidem	Flumazenil
Cyanide	O2  + Amyl nitrite + sodium thiosulphate
Hydrogen sulphide	Amyl nitrite
Carbon monoxide	Hyperbaric O2
Ethylene Glycol	Fomepizole
Iron	Desferrioxamine
Methanol	Fomepizole or ethanol
Salicylates	Alkaline diuresis with sodium bicarbonate
Isoniazid	Pyridoxine
Methemoglobinemia	High Dose O2 + Methylene Blue
Lithium	Hemodialysis
Opioids	Naloxone
Serotonin syndrome	Cyproheptadine or chlorpromazine
Scorpion sting	Parazosin
Calcium channel blockers	Calcium
Theophylline / Caffeine	Esmolol

Umbilical Ligaments & folds

Median Umbilical Ligament

·         Remnant of embryonic urachus

·         extends from apex of bladder to umbilicus, on the deep surface of anterior abdominal wall

·         Unpaired

·         covered by median umbilical folds

·         used as a landmark for surgeons who are performing laparoscopy such as laparoscopic inguinal hernia repairs,other than that it has no function in a born human

Medial Umbilical Ligament

·         Remnant of fetal umbilical arteries which serves no function except for part that becomes adult umbilical artery  

·         Paired

·         on the deep surface of the anterior abdominal wall

·         covered by medial umbilical fold (plica umbilicalis medialis ) 

·         landmark for surgeons during laparoscopic inguinal hernia

Lateral Umbilical Ligament

·         Inferior epigastric artery - medial branch of distal segment of External Iliac Artery

·         ascends along medial margin of deep inguinal ring 

·         continues b/w rectus abdominis muscle & posterior lamina of sheath

·         then appears on the anterior parietal peritoneum to create Lateral Umbilical Ligament

·         not always readily visualised, but knowledge of its location is important to avoid injury to vessels

Lateral Umbilical Fold

·         Lateral umbilical fold overlies the inferior epigastric artery & accompanying veins

·         Unlike median & medial umbilical folds the contents of lateral umbilical fold remains functional after birth 

·         extends from from deep inguinal ring to arcuate line

·         lateral umbilical fold - reference site to classify hernia 

·         Direct Hernia - medial to lateral umbilical fold 

·         Indirect Hernia - lateral to lateral umbilical fold due to placement of opening of deep inguinal ring in the space lateral to lateral umbilical fold, which allows the passage of ductus deferens,testicular artery & spermatic cord and its contents in men & round ligament of uterus in women.

Human Mitochondrial DNA

Features of Human Mitochondrial DNA

                           

·         Is circular, double-stranded, and composed of heavy (H) and light (L) chains or strands 

·         Contains 16,569 bp

·         Encodes 13 protein subunits of the respiratory chain (of a total of about 67

                Seven subunits of NADH dehydrogenase (complex I)

                Cytochrome b of complex III
                Three subunits of cytochrome oxidase (complex IV)
                Two subunits of ATP synthase

·         Encodes large (16S) and small (12S) mt ribosomal RNAs

·         Encodes 22 mt tRNA molecules

      Genetic code differs slightly from the standard code

                UGA (standard stop codon) is read as Trp
                AGA and AGG (standard codons for Arg) are read as stop codons

·         Contains very few untranslated sequences

·         High mutation rate (5 to 10 times that of nuclear DNA)

·         Comparisons of mtDNA sequences provide evidence about evolutionary origins of primates and other species

Mitochondrial DNA Inheritance

·         inheritance is only via the maternal line as the sperm contributes no cytoplasm to the zygote

·         all children of affected males will not inherit the diseases

·         all children of affected females will inherit it

·         generally encode rare neurological diseases

·         poor genotype:phenotype correlation - within a tissue or cell there can be different mitochondrial populations - this is known as heteroplasmy)

Histology

·         muscle biopsy classically shows 'red, ragged fibres' due to increased number of mitochondria

Mitochondrial DNA disorders :

·         Leber's hereditary optic neuropathy (LHON) - Bilateral subacute or acute painless optic atrophy

·         MELAS syndrome: mitochondrial encephalomyopathy lactic acidosis and stroke-like episodes

·         MERRF syndrome: myoclonus epilepsy with ragged-red fibres in muscles, ataxia, 

·         Kearns-Sayre syndrome: onset in patients < 20 years old, external ophthalmoplegia, retinitis pigmentosa, heart block, ataxia

·         NARP, Leigh disease - neurogenic weakness, ataxia, retinitis pigmentosa

·         Pearson syndrome - pancreatic insufficiency, pancytopenia, lactic acidosis 

·         Chronic progressive external ophthalmoplegia - late-onset bilateral ptosis, ophthalmoplegia, proximal muscle weakness, exercise intolerance

                           

                                  

History Taking

Approach  to a patient for history taking and examination

 

·         Interviewer should wear white coat with named badge. He should address the patient with Mr/Mrs/Dr/Ms, wish him.

·         Bed around the patient and surroundings are properly lighted. The patient’s privacy should be assured

·         The interviewer must be sure that the patient is not deaf or dumb. Patient should lie in comfortable position or sitting in the chair.

·         Interviewer should sit in front of the patient in a chair, 3 to 4 feet from the patient in relaxed position

·         In case of bed-ridden patient, elevate the head end of the bed and try to lower the bedside rail, so that it cannot interrupt the interview

·         After introduction, interviewer should ask the patient—“For which problem, he has been admitted here?” If the patient tells the interviewer to see his hospital records, he should ask the patient about his previous health, followed by remodeling of first question “he want to hear from the patient’s own voice?”

·         After interviewer asks the patient to narrate the chief complaint in a specific format, followed by past history, social, personal, drug, dietary history and so on

Patient’s Details

It includes:

·         Name

·         Age

·         Sex

·         Religion

·         Address

·         Occupation

·         Date of admission

·         Date of examination

Chief Complaints

·         It is brief statement with duration for which he or she has been admitted for in specified institution.

·          If the chief complaint is more than one, then they should be arranged in chronological order with respect to duration.  For example,

·         ™Pain in upper abdomen for 4 days™

·            Nausea and vomiting for 2 days

·            Loose motion for 1 day.

History of Present Illness

It is important to know that the patient was well before the onset of  illness. Patient often does not remember the exact date of onset and duration of illness. In that case, it is necessary for the interviewer to correlate the symptom with any known or memorable event.

Each principal symptom has to be described in relation to:

OLD CARTS: It means:

O = Onset

L = Location

D = Duration

C = Character

A = Aggravating/relieving factors

R = Radiation

T = Timing

S = Associated factors.

If the patient has more than one complaint, then according to the chronology, they should be described  in separate paragraph. During the present illness, if any medication is taken, it should be described  in generic name with specific dosage, route and frequency. If any remedy or aggravation occurred with these medications, this should also be described. Any allergy due to intake of recent medication such as, skin rash, nausea, if present or not, it should also be described.

History of Past Illness

It should be divided into two parts:

1. Childhood history:

Communicable diseases: Chickenpox, measles, rubella, mumps, whooping cough, if occurred, the time of occurrence, course and treatment.

Any severe bacterial illness involving lung, gastrointestinal tract, nervous system—should be thoroughly interviewed.

2. Adult illness: It should be divided into:

Medical history:Acute or chronic infection, Asthma, Any disease requiring hospitalization.

Surgical history: Any type of operation—open, laparoscopic or endoscopic.

Gynecological history: Any type of major or minor operation.

Past medical illness

Consists  of three components:

1. Diagnosis: What was the diagnosis ?

2. Evidence: What where the symptoms ?

3. Management: What was the medical management of the illness ( Antibiotics / Surgery ) ?

History of admission in any hospital for medical, surgical, obstretical, gynecological or psychological reasons

The importance of taking past medical history is to link this with present history of illness, if any.

Any surgical procedure, date, hospital name, if possible, should be obtained.

Family History

It includes the history of:

·         Parents

·         Grandparents

·         Siblings

·         Children

·         Grandchildren.

The diseases to be enquired are:

·         Cardiac—coronary artery disease, hypertension

·         Renal—chronic renal disease

·         Endocrine—thyroid disease, diabetes

·         Lung—tuberculosis

·         Skin—atopic dermatitis

·         CNS—convulsion, strokes

·         Metabolic—hyperlipidemia.

Personal History

 Educational status: Age of onset of schooling, upto which level the patient is educated

 Occupational status.

 Marital status:

·         Whether the patient is married or not?

·         If married, for how many years he is married?

·         How many issues are present with this patient?

·         Whether the siblings are suffering from any illness?

·         Whether the illness is correlated with the patient’s present complaint?

 Dietary history: The following questions are to be asked to the patient:

·         Whether the patient is vegetarian or nonvegetarian?

·         What is his routine diet?

·         Does he take diet with high fiber content, e.g. whole grain, bread, cereal, fresh fruit, vegetables, bran?

·         Does he take extra salt in his diet?

·         How much saturated fat present in his diet?

·         How much and type of fish or meat (chicken, mutton) present in his daily diet?

·         Does he take boiled food or fried food? If so, when?

·         Does he take caffeine containing food daily, if yes, what is the frequency of intake?

For example, coffee, tea, cola, chocolate. Caffeine containing foods are responsible for fatigue, palpitation, lightheadedness, headache, irritability.

·         Whether the patient has special or restricted diet?

·         What sort of oils is used during cooking of food?

·         How often the patient uses to take outside food?

·         Patient with diabetes mellitus, the following questions should be required:

·         Insulin or oral antidiabetic drugs

·         Dietary restriction

·         Any past history of hypoglycemia

·         What type of food exchanges the patient uses to follow?

Sleep history

Bowel & Bladder movements  :

Dietary allergy history: It is necessary to ask the patient about allergy to food. Common foods those are associated with allergy are peanuts, shellfish, eggs, brinjal, soy, milk.

 Addiction history:

Smoking: The question should be:

·         For how many years, the patient is taking cigarette?

·         How many cigarettes per day he is taking?

·         What type of tobacco he is taking, cigarette, cigar, bidi, chewing tobacco?

·         Does he change the type of cigarette in recent years?

·         Did he try to stop the smoking? If so, what was his feeling?

·         Does the smoking relate with bowel movement or cheerfulness?

Alcohol history: The question should be:

·         What type of alcohol?

·         How much alcohol taken by the patient per day?

From the history of alcohol intake, the interviewer can correlate the present illness with the alcohol intake, e.g. if the patient is suffering from jaundice, or severe pain in upper abdomen, it may be due to alcohol related hepatitis, or acute pancreatitis or alcohol related gastritis. It may relate with the patient’s emotional reaction

Heavy alcohol intake may be associated with the following medical problems:

·         Coronary artery disease

·         Alcohol-related liver disease

·         Cardiac arrhythmias

·         Hemorrhagic or ischemic strokes

·         Hypertension

·         Pancreatitis.

CAGE questioning, this is the screening questions for alcohol abuse:

C = Has he ever felt the need to cut down of alcohol drinking?

A = Has the patient ever been annoyed by criticism of his drinking?

G = Has he felt guilty conscious for drinking?

E = Has he ever taken alcohol after rising from the bed (eye opening) in the morning to become steady and get rid of the hang over?

Two or more positive answers to CAGE questionnaire suggest alcohol misuse—sensitivity is 43 to 94 percent,

specificity is 70 to 96 percent.

Detection of alcohol misuse can be done by getting history of:

·         Syncope

·         Convulsion

·         Accidents

·         Conflict in job

·         Relationship with others.

History of drug abuse: In contrast to alcohol abuser, drug abusers are more likely to magnify their use. The following

questions should be asked regarding drug abuse:

·         What types of drug used?

·         How long he has started?

·         For how many days, he is taking drug heavily?

·         Approximately when he has started drug abuse?

·         Why he has started to take the drug heavily?

·         At which time, he uses to take the drug?

·         What is his feeling after taking the drug?

·         Whether he has tried to get rid of the drug?

·         What is his feeling after leaving the drug abuse temporarily?

·         Is there any convulsion after withdrawal of the drug?

·         Does he take the drug in single dose or in divided doses?

·         Is he taking only single drug for addiction?

 Psychosocial and Spiritual History

·         Education

·         Life experience

·         Relationship with other individual

·         Schooling

·         Religious belief

Occupational and Environmental History

One may incorrectly describes the illness due to some other cause, because of  long  latency between exposure and onset of illness. Many occupational diseases have been discovered  up till now. Some of these are:

·         Bladder carcinoma—in aniline dye worker

·         Malignant mesothelioma—person exposed to asbestos

·         Malignant neoplasm in nasal cavities—woodworkers

·         Hepatic angiosarcoma—person exposed to vinyl chloride

·         Pneumoconiosis—coal workers

·         Silicosis—sandblasters

·         Bassinosis—cotton industry workers

·         Ornithosis—bird breeders

·         Bronchial asthma—person exposed to dust, pollen

·         Khangri cancer—in the inner lip, exposed to tobacco chewers

·         Toxic hepatitis—workers of plastic industries

·         Friedlander’s pneumonia—exposed to pigeon and  parrot danders.

Environmental pollution is also responsible for mortality and morbidity of human being world- wide.

·         Chernobyl—due to high radiation

·         Minamata bay, Japan—due to mercury poisoning

·         Hopewell, Virginia—due to poisoning with pesticides chlordecone

·         Bhopal, India—due to gas leak methylisocyanate

To recognize the disease as environmental or occupational hazards, the following interrogations are necessary:

·         What is his job?

·         How long he is in his job?

·         In his job, with what material he is working?

·         Does he work with proper precaution during his work?

·         Description of surroundings around his working place.

·         Where is his house? Whether his house is nearer to the coal mine, shipyard, any factories?

·         How long he is living in that place?

·         What is his hobby? Whether he likes bird or animal?

·         If bird, which bird, and if animal, which animal?

·         Whether he is working with lead, asbestos, fumes, dust, flower?

Sexual, Gynecological and Reproductive History

Menstrual history:

·         Age of menarche

·         Menstrual flow

·         Duration of flow

·         Any pain preceding or during menstruation

·         If yes, when it subsides?

Obstetric history:

·         Number of pregnancies

·         Number of abortion

·         Number of deliveries

·         Age of 1st pregnancy

·         Frequency of pregnancies

·         Abortion—whether spontaneous or, induced

·         Complication of pregnancy

·         Postpartum condition of the patient.

Drug History

·         Any history of intake of drug with dosage, duration, frequency,

·         Any history of associated drug allergy should be taken.

·         If there is drug allergy, avoid the drug throughout the life

·         If any flare up of previous disease, which may indicate inadequately treated disease, may be in the form of dosage or duration of treatment

·         In case of chronic disease, like, hypertension, diabetes, hyperlipidemia, whether the drugs are continued or not  If not, the present illness may be the consequences of above chronic disease.

·         Drug may produce drug and nutrient interactions. This should be interrogated to the patient during interview. So the following questions should be asked to the patient: 

                  Whether the patient is taking minerals, herbs or dietary supplements for   any ailment, if so, why?

·         What is the dose of the above drugs?

·         Whether the patient experience any side effect during this drug intake?

·         Who is the person responsible for the above prescription of the drug?

Drug may influence the nutrients in the following ways:

·         Avoiding intake of the food—due to nausea, vomiting or feeling of bad smell of the food.

·         Abnormal absorption of the food is due to:

·         Increased intestinal motility

·         Competitive inhibition of the food by the drugs

·         Alteration of the intestinal pH

·         Alteration in excretion.

Drugs Nutrients affected

Immunization History

 From birth to childhood age, whether all immunizations were done or not. If done, the interviewer should see the immunization card

In adult, yearly influenza vaccination should be done in patient with cardiovascular, pulmonary, renal, hematological disorders.