When a patient with type 2 diabetes and obesity presents with abnormal liver function tests, the most probable diagnosis is non-alcoholic fatty liver disease. To confirm this diagnosis, the patient will need to undergo a liver screen, ultrasound, and liver biopsy. While haemochromatosis should be considered in patients with both abnormal LFTs and diabetes, a normal ferritin level makes this diagnosis less likely.

Non-Alcoholic Fatty Liver Disease: Causes, Features, and Management

Non-alcoholic fatty liver disease (NAFLD) is a prevalent liver disease in developed countries, primarily caused by obesity. It encompasses a range of conditions, from simple steatosis (fat accumulation in the liver) to steatohepatitis (fat with inflammation) and may progress to fibrosis and liver cirrhosis. Insulin resistance is believed to be the primary mechanism leading to steatosis, making NAFLD a hepatic manifestation of metabolic syndrome. Non-alcoholic steatohepatitis (NASH) is a type of liver damage similar to alcoholic hepatitis but occurs in the absence of alcohol abuse. It affects around 3-4% of the general population and may be responsible for some cases of cryptogenic cirrhosis.

NAFLD is usually asymptomatic, but hepatomegaly, increased echogenicity on ultrasound, and elevated ALT levels are common features. The enhanced liver fibrosis (ELF) blood test is recommended by NICE to check for advanced fibrosis in patients with incidental NAFLD. If the ELF blood test is not available, non-invasive tests such as the FIB4 score or NAFLD fibrosis score, in combination with a FibroScan, may be used to assess the severity of fibrosis. Patients with advanced fibrosis should be referred to a liver specialist for further evaluation, which may include a liver biopsy to stage the disease more accurately.

The mainstay of NAFLD treatment is lifestyle changes, particularly weight loss, and monitoring. Research is ongoing into the role of gastric banding and insulin-sensitizing drugs such as metformin and pioglitazone. While there is no evidence to support screening for NAFLD in adults, NICE guidelines recommend the management of incidental NAFLD findings.

To effectively manage sickle cell crisis, it is essential to administer analgesia, oxygen, and IV fluids. In addition, antibiotics may be necessary if an infection is suspected, and transfusion may be required if the patient’s Hb levels are low.

It is not advisable to simply monitor patients without providing any treatment, as this would result in significant pain and discomfort.

The most effective approach involves a combination of oxygen, fluids, and analgesia. Pain management is crucial, as the blockage of blood vessels by sickle-shaped red blood cells prevents the delivery of oxygen and blood to the tissues, resulting in pain. Oxygen supplementation is necessary to alleviate this pain, and IV fluids can help to slow or halt the sickling process. None of these components alone would be sufficient in managing pain, but together they form a comprehensive approach to pain management.

Managing Sickle-Cell Crises

Sickle-cell crises can be managed through various interventions. General management includes providing analgesia, rehydration, and oxygen. Antibiotics may also be considered if there is evidence of infection. Blood transfusion may be necessary for severe or symptomatic anemia, pregnancy, or pre-operative cases. However, it is important not to rapidly reduce the percentage of Hb S containing cells.

In cases of acute vaso-occlusive crisis, such as stroke, acute chest syndrome, multiorgan failure, or splenic sequestration crisis, exchange transfusion may be necessary. This involves rapidly reducing the percentage of Hb S containing cells. It is important to note that the management of sickle-cell crises should be tailored to the individual patient’s needs and medical history. Proper management can help alleviate symptoms and prevent complications.

Common Genetic Disorders and Their Prenatal Ultrasound Findings

Prenatal ultrasound is a valuable tool for detecting genetic disorders in fetuses. Here are some common genetic disorders and their associated ultrasound findings:

1. Patau Syndrome (Trisomy 13): This disorder has a prevalence of 1 per 6500 births. Fetuses with Trisomy 13 may show brain anomalies, midfacial hypoplasia, ventriculomegaly, microcephaly, cleft lip and palate, and cardiac defects.

2. Cystic Fibrosis (CF): Hyperechogenic fetal bowel is often associated with severe diseases, notably CF.

3. Down Syndrome: 20% of all second-trimester Down syndrome fetuses have major structural anomalies, including polyhydramnios, double bubble, and large cardiac septal defects.

4. Klinefelter Syndrome: This disorder results from two or more X chromosomes in boys and may cause infertility and small testicles.

5. Potter Syndrome: This disorder is suspected whenever the combination of intrauterine growth retardation and severe oligohydramnios is seen. It consists of pulmonary hypoplasia, growth restriction, abnormal facies, and limb abnormalities.

In conclusion, prenatal ultrasound can help detect genetic disorders in fetuses, allowing for early intervention and management.

It is highly probable that the individual is suffering from liver failure as all clotting factors, except for factor VIII, are below normal levels. In cases of liver failure, both PT and APTT may be prolonged. Haemophilia A and B are unlikely as they result in deficiencies of specific clotting factors, whereas Von Willebrand disease may have low levels of Von Willebrand factor but the other factors remain unaffected. Disseminated intravascular coagulation, on the other hand, leads to depletion of all clotting factors.

Coagulopathy in Liver Disease: Paradoxical Supra-normal Factor VIII and Increased Thrombosis Risk

In liver failure, the levels of all clotting factors decrease except for factor VIII, which paradoxically increases. This is because factor VIII is synthesized not only in hepatic endothelial cells but also in endothelial cells throughout the body. Moreover, good hepatic function is required for the rapid clearance of activated factor VIII from the bloodstream, leading to further increases in circulating factor VIII. Despite conventional coagulation studies suggesting an increased risk of bleeding, patients with chronic liver disease are paradoxically at an increased risk of thrombosis formation. This is due to several factors, including reduced synthesis of natural anticoagulants such as protein C, protein S, and anti-thrombin, which are all essential for preventing thrombosis.

Reference
Tripodi et al. An imbalance of pro- vs anti-coagulation factors in plasma from patients with cirrhosis. Gastroenterology. 2009 Dec;137(6):2105-11.

Distinguishing Multiple Myeloma from Other Bone Diseases

Multiple Myeloma: A Malignant Disease of Plasma Cells

Multiple myeloma is a type of cancer that affects the plasma cells in the bone marrow. It is more common in black Africans and rare in Asians, with a median age of onset over 60. Patients may not show any symptoms and are often diagnosed through routine blood tests. However, they are more susceptible to infections and may have low white blood cell counts. Elevated levels of ESR and CRP are almost always present. Diagnosis is confirmed when two out of three of the following are present: paraproteinaemia or Bence Jones protein, radiological evidence of lytic bone lesions, and an increase in bone marrow plasma cells. Patients may experience bone pain, lethargy, thirst, and anaemia, which are all signs of multiple myeloma.

Calcium Pyrophosphate Arthropathy: Shedding of Crystals into Joints

Calcium pyrophosphate arthropathy, also known as pseudogout, is caused by the shedding of calcium pyrophosphate crystals into the joint. It typically presents as an acute-onset monoarticular arthritis, usually in the knee or wrist. The joint will be hot, red, tender, and swollen. Rhomboid-shaped crystals that are weakly positively birefringent under polarised light will be visible in synovial fluid.

Osteoporosis: Fragility Fractures

Osteoporosis is characterised by fragility fractures, such as vertebral crush fractures, Colles fractures, and fractures of the proximal femur. It is uncommon in men at this age, unless associated with hypogonadism. Anaemia and elevated ESR are not seen in osteoporosis.

Osteoarthritis: Joint Pain and Stiffness

Osteoarthritis presents with joint pain, stiffness, and reduced function. The weight-bearing joints, such as the hip and knee, and the small joints of the hand are commonly affected. Patients do not experience symptoms such as thirst and lethargy, which are due to hypercalcaemia. Blood biochemistry is normal in osteoarthritis.

Paget’s Disease of Bone: Bone Remodelling

Paget’s disease of the bone is rare in individuals under 40 years old. It is characterised by bone pain, deformity, fragility fractures, and complications from nerve compression

What spirometry result is expected in alpha-1 antitrypsin deficiency?

Alpha-1 antitrypsin deficiency will result in an obstructive pattern on spirometry, similar to chronic obstructive pulmonary disease (COPD). The two important factors to consider in spirometry are the FEV1 and the FEV1/FVC ratio. In obstructive disease, the FEV1 is reduced due to narrowed airways, while the FVC remains normal. This results in a reduced FEV1/FVC ratio. Therefore, in alpha-1 antitrypsin deficiency, we would expect to see a reduced FEV1 and FEV1/FVC ratio on spirometry.

Understanding Alpha-1 Antitrypsin Deficiency

Alpha-1 antitrypsin deficiency is a genetic condition that occurs when the liver fails to produce enough of a protein called alpha-1 antitrypsin (A1AT). A1AT is responsible for protecting cells from enzymes that can cause damage, such as neutrophil elastase. This deficiency is inherited in an autosomal recessive or co-dominant fashion, with alleles classified by their electrophoretic mobility as M for normal, S for slow, and Z for very slow. The normal genotype is PiMM, while heterozygous individuals have PiMZ. Homozygous PiSS individuals have 50% normal A1AT levels, while homozygous PiZZ individuals have only 10% normal A1AT levels.

The classic manifestation of A1AT deficiency is emphysema, which is a type of chronic obstructive pulmonary disease. This condition is most commonly seen in young, non-smoking patients. However, the evidence base is conflicting regarding the risk of emphysema. Non-smokers with A1AT deficiency are at a lower risk of developing emphysema, but they may pass on the A1AT gene to their children. Patients with A1AT deficiency who manifest disease usually have the PiZZ genotype.

In addition to emphysema, A1AT deficiency can also cause liver problems such as cirrhosis and hepatocellular carcinoma in adults, and cholestasis in children. Diagnosis is made by measuring A1AT concentrations and performing spirometry, which typically shows an obstructive pattern. Management includes avoiding smoking, supportive measures such as bronchodilators and physiotherapy, and intravenous A1AT protein concentrates. In severe cases, lung volume reduction surgery or lung transplantation may be necessary.

Termination of Pregnancy in the UK

The UK’s current abortion law is based on the 1967 Abortion Act, which was amended in 1990 to reduce the upper limit for termination from 28 weeks to 24 weeks gestation. To perform an abortion, two registered medical practitioners must sign a legal document, except in emergencies where only one is needed. The procedure must be carried out by a registered medical practitioner in an NHS hospital or licensed premise.

The method used to terminate a pregnancy depends on the gestation period. For pregnancies less than nine weeks, mifepristone (an anti-progestogen) is administered, followed by prostaglandins 48 hours later to stimulate uterine contractions. For pregnancies less than 13 weeks, surgical dilation and suction of uterine contents is used. For pregnancies more than 15 weeks, surgical dilation and evacuation of uterine contents or late medical abortion (inducing ‘mini-labour’) is used.

The 1967 Abortion Act outlines the circumstances under which a person shall not be guilty of an offence under the law relating to abortion. These include if two registered medical practitioners are of the opinion, formed in good faith, that the pregnancy has not exceeded its 24th week and that the continuance of the pregnancy would involve risk, greater than if the pregnancy were terminated, of injury to the physical or mental health of the pregnant woman or any existing children of her family. The limits do not apply in cases where it is necessary to save the life of the woman, there is evidence of extreme fetal abnormality, or there is a risk of serious physical or mental injury to the woman.

Understanding Contraception: A Basic Overview

Contraception has come a long way in the past 50 years, with the development of effective methods being one of the most significant advancements in medicine. There are various types of contraception available, including barrier methods, daily methods, and long-acting methods of reversible contraception (LARCs).

Barrier methods, such as condoms, physically block sperm from reaching the egg. While they can help protect against sexually transmitted infections (STIs), their success rate is relatively low, particularly when used by young people.

Daily methods include the combined oral contraceptive pill, which inhibits ovulation, and the progesterone-only pill, which thickens cervical mucus. However, the combined pill increases the risk of venous thromboembolism and breast and cervical cancer.

LARCs include implantable contraceptives and injectable contraceptives, which both inhibit ovulation and thicken cervical mucus. The implantable contraceptive lasts for three years, while the injectable contraceptive lasts for 12 weeks. The intrauterine system (IUS) and intrauterine device (IUD) are also LARCs, with the IUS preventing endometrial proliferation and thickening cervical mucus, and the IUD decreasing sperm motility and survival.

It is important to note that each method of contraception has its own set of benefits and risks, and it is essential to consult with a healthcare provider to determine the best option for individual needs and circumstances.

If hydrogen peroxide is not appropriate, topical fusidic acid can be used for impetigo.

Understanding Impetigo: Causes, Symptoms, and Management

Impetigo is a common bacterial skin infection that affects both children and adults. It is caused by either Staphylococcus aureus or Streptococcus pyogenes and can develop anywhere on the body, but lesions tend to occur on the face, flexures, and limbs not covered by clothing. The infection can be a primary infection or a complication of an existing skin condition such as eczema, scabies, or insect bites. Impetigo is highly contagious and can spread through direct contact with discharges from the scabs of an infected person or indirectly through toys, clothing, equipment, and the environment.

The symptoms of impetigo include ‘golden’, crusted skin lesions typically found around the mouth. The infection can be managed with limited, localized disease by using hydrogen peroxide 1% cream or topical antibiotic creams such as fusidic acid or mupirocin. However, if the disease is extensive, oral flucloxacillin or oral erythromycin may be prescribed. It is important to note that MRSA is not susceptible to either fusidic acid or retapamulin, so topical mupirocin should be used in this situation.

Children with impetigo should be excluded from school until the lesions are crusted and healed or 48 hours after commencing antibiotic treatment. It is also important to practice good hygiene, such as washing hands regularly and avoiding close contact with infected individuals, to prevent the spread of impetigo. By understanding the causes, symptoms, and management of impetigo, individuals can take steps to prevent and treat this common bacterial skin infection.

Differential Diagnosis for a Patient with Itching and Skin Lesions: Scabies, Atopic Dermatitis, Erythema Infectiosum, Folliculitis, and Keratosis Pilaris

A patient presents with itching between the web spaces and in the groin, which has been ongoing for three to four weeks. The patient reports sexual intercourse as a possible mode of transmission. The differential diagnosis includes scabies, atopic dermatitis, erythema infectiosum, folliculitis, and keratosis pilaris.

Scabies is the most likely diagnosis, as it presents with itching after a delay of three to four weeks following skin-to-skin contact. A washable felt-tip can be used to identify the burrows of the scabies mites, and treatment involves a typical topical agent such as permethrin cream.

Atopic dermatitis is an unlikely diagnosis, as it typically presents with a rash/itch on the flexor aspects of the joints and is unrelated to sexual intercourse.

Erythema infectiosum is a doubtful diagnosis, as it primarily affects children and presents with a slapped cheek appearance and other symptoms such as fever and headache.

Folliculitis is an unlikely diagnosis, as it presents with pinpoint erythematous lesions on the chest, face, scalp, or back and is unrelated to sexual intercourse.

Keratosis pilaris is an unlikely diagnosis, as it typically affects the upper arms, buttocks, and thighs and presents with small white lesions that make the skin feel rough. It is also unrelated to sexual activity.

In conclusion, scabies is the most likely diagnosis for this patient’s symptoms, and treatment with a topical agent such as permethrin cream is recommended.