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Week 1-2: SHOCK (Hypovolaemic Shock) Definition Shock is the syndrome (a constellation of symptoms and signs) that results from reduced perfusion (blood flow) to the tissues of the body. Pathogenesis Shock is the final common pathway for a number of potentially lethal clinical events, including severe haemorrhage, extensive trauma or burns, large MI, pulmonary embolism and microbial sepsis. Shock has many causes that can be grouped: (i) Cardiogenic: shock due to myocardial pump failure – MI, ventricular arrythmias, outflow obstruction (pulmonary embolism), (ii) Hypovolaemic: shock due to deficient circulating blood volume – significant haemorrhage, fluid loss from severe burns, (iii) Distributive/Toxic: shock due to expansion of the volume of the vascular system without a corresponding increase in the circulating blood volume – systemic microbial infection. Clinical Features The usual signs are a weak rapid pulse (due to low blood pressure and rapid heart rate), cool, clammy cyanotic skin, with the patient experiencing symptoms of air hunger and a feeling of impending doom. Morphology Regardless of its underlying pathology, shock gives rise to systemic hypoperfusion caused by reduction in either CO or circulating blood volume. The end results are hypotension, followed by impaired tissue perfusion and cellular hypoxia. Although hypoxic and metabolic effects of hypoperfusion initially cause only reversible cellular injury, persistence of shock eventually leads to irreversible tissue injury and death. Hypovolaemic Shock Morphology blood volume systemic filling pressure venous return CO tissue perfusion. If about 10% of the blood volume is lost, compensatory mechanisms may be adequate but after a greater blood loss, shock may progress irreversibly death. Compensatory mechanisms include: Short term - seconds to minutes in onset Autoregulation Increased sympathetic activity from baroreceptor reflex with reflex tachycardia and vasoconstriction (except brain & heart, most marked in skin, kidneys) Central ischaemic response (if mean arterial pressure <50-60mmHg) Medium term - minutes to hours in onset Fluid redistribution from tissues back into capillaries Circulating vasoactive substances o adrenaline/ noradrenaline o vasopressin o angiotensin II/ aldosterone Long term - continuing for days Restoration of salt and water balance through o kidney response o thirst o hormonal activity o erythropoiesis Treatment IV fluids – colloids (fluid with protein products) and crystalloids (Saline) O2 admin Rx cause – haem Blood Loss Short term comp Med term comp Long term comp MAP CO TPR SNS Activity VC SV HR Venous Ret SNS Activity Blood Viscosity # of RBC Local Metabolic Control Respiratory Activity Shivering Blood Vol Vasopressin & Angiotensin II Fluid shifts into caps NaCl and H2O Balance Vasopressin & RAAS Erythropoiesis Week 3: ACNE Definition & Epidemiology Acne is a reasonably common facial rash occurring in adolescence and sometimes into early adult life. It is seen in both males and females, but males tend to suffer from more severe forms of the disease. Other Useful Definitions Macule: Circumscribed lesion of up to 5mm in diameter, characterized by flatness. Papule: Elevated dome-shaped or flat-topped lesion 5mm or less across. Nodule: Elevated lesion with spherical contour greater than 5mm across. Vesicle: Fluid filled raised lesion 5mm or less. Bulla: Fluid filled raised lesion greater than 5mm across. Pustule: Discrete, pus filled, raised lesion. Wheal: Itchy, transient, elevated leasion with variable blanching and erythemo formed as the result of dermal oedema. Scale: Dry, horny, platelike excresence; usually DT imperfect cornification. Excoriation: traumatic lesion characterized by breakage of epidermis causing raw linea area (often self induced). Erosion: Discontinuity of the skin exhibiting incomplete loss of epidermis. Ulceration: Discontinuity of the skin exhibiting complete loss of epidermis, often portions of dermis and even subcutaneous fat. Pathogenesis Four key components contribute to the development of acne: 1. Changes in keratinisation of the lower portion of the infundibulum with the development of a keratin plug blocking outflow of sebum to the skins surface, 2. size of sebaceous glands with puberty or activity DT hormonal stimulation, 3. Propionibacterium acnes – lipase-synthesising bacteria colonising the hair follicle, converting lipids in sebum to pro-inflammatory fatty acids, 4. Inflammation in the follicle associated with the release of cytotoxic and chemotactic factors The above components may be induced or exacerbated by drugs (corticosteroids, testosterone, contraceptives), occupational contactants (Macca’s), occlusive conditions including heavy clothing and tropical climates. Clinical Features Acne presents in areas rich in sebaceous glands – face, back and sternal areas. The skin may appear greasy and inflamed Deep-seated nodulocystic lesions and dermal inflammation can cause acne scarring Morphology Divided into non-inflammatory and inflammatory types: Infalmmatory – Erythematous papules, nodules and pustules Non-inflammatory – Open comedones (blackheads: follicular papules with central black plug – black DT oxidation of melalin pigment) and closed comedones (whiteheads- follicular papules without central plug). May lead to inflam type. Extensive acute and chronic inflammation accompanies follicular rupture. Dermal abscesses may form in association with the rupture. Treatment Aimed at: Sebum Production bacteria inflammation Normalising duct keratinisation Rx CLASS Topical Retinoids Topical Antibiotics BPO (Benzoyl Peroxide) Oral Antibiotics Hormonal Therapy (OCP) Keratolytic (Salicylic acid & sulphur-based) ACTION EXAMPLE Inhibit microcomedo formation by reg the follicular keratinocyte. Normalise keratinocyte desquamation by affecting follicular turnover and cell maturation. Anti-inflam properties affecting immune response, inflam cell migration & mediators. Reduce bacterial infection but problems with resistance common Help to resolve inflammatory acne Most potent topical antimicrobial with rapid bactericidal action resulting in rapid reduction in bacterial organisms. Cause a reduction in resident skin bacteria, P acnes and Staph epidermidis. Also have intrinsic anti-inflam properties Decrease the amount of circulating androgens which in turn results in a decrease in sebum production These preparations are keratolytics (peeling agents) that can unblock pores by removing keratin plugs. Cytokine production Neutrophil recruitment Rupture of sebum in dermis Inflammatory Pustule Papule Protease production & hydrolysis of lipids to proinflam fatty acids Comedone Tretinoin Adapalene Tazarotene Clindamycin Many diff formulations washes1-10% Tetracycline, Doxycycline Minocycline Diane Juliet Clearasil DermaVeen Propionibacterium acnes Pilosebaceous duct blockage Sebum production DT sebaceous hyperplasia Pilosebaceous duct hypercornification Androgens in puberty Genetic susceptability Week 4: SCID Definition and Epidemiology Severe combined immunodeficiency disease (SCID) represents a constellation of genetically distinct syndromes all having common defects in both humeroal and cell-mediated immune responses. More common in boys. Pathogenesis SCID is a primary immunodeficiency disorder determined by genetics. The most common form is Xlinked (The reason why more boys suffer from SCID) but autosomal recessive defects also cause the disease. X-linked – Profound defect in the earliest stages of lymphocyte development especially T-cell development. T-cell numbers are greatly reduced and although B-cell numbers are normal antibody synthesis is impaired DT lack of help form T-cells. Autosomal Recessive – Deficiency in enzyme Adenosine Deaminase causing accumulation of toxic products that affect immature lymphocytes, esp T-cells. Greater reduction in T-cell numbers than B-cell numbers. Clinical Features Affected infants present with prominent thrush, nappy rash and failure to thrive. Morphology SCID pts are extremely susceptible to recurrent, severe infections by a wide range of pathogens. Hypoplastic lymphoid tissue. Investigations Blood tests and histology of lymph tissue Treatment Without a bone marrow transplant death usually occurs in the 1st year of life. Other Primary Genetic immunodeficient Dzs Hyper IgM syndrome – Functionally abnorm T-cells DiGeorge Syndrome – T-cell deficiency DT failure of d’ment of pharyngeal pouches – hypoplasia of thymusGenetic deficiency of complement system Failure to Thrive The following diagnostic criteria have proved helpful in identifying inadequate weight gain in infants: 1: Failure to regain birth weight by 3 weeks of age. 2: Weight loss of greater than 10% of birth weight by 2 weeks of age. 3: Weight dropping below the third percentile. 4: Deceleration of growth from a previous established pattern of weight gain. 5: Evidence of malnutrition on examination, eg) min subcutaneous fat or wasted buttocks. Week 5: HEPATITIS Definition Viral hepatitis applies to liver infections resulting in inflammation caused by several unrelated viruses. Viral Agent Hep A Enterovirus Hep B Hepadna virus Hep C Unclassified Transmission Faecal-oral Incubation Type 2 – 6 wks Acute or inapparent None Parenteral/ close contact 2 – 26 wks Acute or persistent >50% No Parenteral/ close contact 4 – 26 wks Acute or persistent 5-10% of acute infects Yes Yes Hep D RNA genome Hep B capsid Parenteral/ close contact 4 – 7 wks Acute or persistent 80% on superinfect Yes No Yes Yes Yes No Yes Yes No HBV Vaccine No Chronic Hepatitis Carrier State Hepatocellular carcinoma Vaccine Hep E Unclassified Waterborne/ Faecal-oral 2 – 8 wks Acute or inapparent None No Pathogenesis Damage to liver is due to a two-fold mechanism: 1. Virus injures liver cells directly (Remember: APUTRAR) 2. Virus triggers a host immune response which then causes inflammation and attack of liver cells by cytotoxic T-cells Clinical Presentation Can show a range of symptoms (Mostly GIT)– Bile in urine, pale stools, jaundice, anorexia, mailase, nausea and vomiting as well as a low grade fever. HAV may be asymptomatic HBV may also present with a rash and joint px Serology + Result Indicates Details HAV-Ag Hep A viral Antigen Present only during acute infection (wks 2-6) HAV-IgM Early Antibodies – Acute infection Appear early @ same time of symptom onset HAV-IgG When NO IgM: Previous exposure OR vaccination IgG provides lifelong immunity against infection HBsAg Active infection & current carrier Anti-HBs HBeAg Immunity via previous infection or immunisation acute, chronic/ resolved infection. NOT marker of vaccine-induced immunity Active Viral Replication The surface antigen of HBV. Usually appears a few weeks PRIOR to symptoms, disappears during covalescence Antibody to the surface antigen. It usually appears AFTER the clinical illness and persists for life. Antibodies to the core antigen HBV DNA Active Viral Replication Hep A Hep B Anti-HBc Antigen derived from the viral core. Ass with infectivity & risk of developing chronic Dz Genome of HBV Hep C Anti HCV Acute/ chronic infection or immunity RT-PCRHCV Current infection Antibodies against the HCV virus. +ve result indicates exposure but doesn’t indicate if infection is present now This test is nec to tell if there is a current infection Acute Hepatitis Four phases: 1. Incubation period: peak infectability occurs in the last few days of the incubation period, 2. Symptomatic preicteric phase: non specific symptoms – malaise, fatigue, nausea, appetite, fever, headaches, muscle and joint aches, 3. Symptomtic icteric phase: Jaundice, pale stools and dark urine all caused by conjugated hyperbilirubinemia along with mildly enlarged, moderately tender liver, 4. Convalescence: Recovery is via generation of a strong T-cell response to viral antigens expressed on infected liver cells. Treatment/Management Provide adequate nutrition, Prevent further damage to the liver (eg OH, drugs etc), Prevent spred of infection to others (Hygiene, sexual activity etc) Fulminant Hepatitis Rarely, cases of acute hepatitis can deteriorate rapidly and cause massive liver necrosis and atrophy. Only Rx is an emergengy liver transplant. Hepatitis Complications Cirrhosis Hepatocellular carcinoma Ascities Liver failure Portal hypertension Week 6: Giardia Lamblia & Diarrhoea Definition and Epidemiology Giardia Lamblia is a flagellate protozoan whose colonisation of the small intestine causes malabsorption and diarrhoea. It is found world wide. Spread (cysts) by faecal-oral route, transmission can be water borne or through animal vectors. Giardia is generally not notifiable unless there is evidence of an outbreak – multiple associated cases within a short time frame. Pathogenesis Generally Giardia lives on the surface of mucosa, in the mucus layer causing: Blanketing over large areas of GI (obstructs absorption) DIRECT DAMAGE (release of proteases and endotoxins) mucous/electrolyte and H20 secretion & absorption of Na+/H20 (body tries to flush out pathogen) There is a structural progression in the damage to the GIT 1st microvillous disruption Disaccharidase activity, Glucose stimulated Na+/Cl/H20 absorption Then macrophage activation and Lymphocyte infiltration villous atrophy and crypt deepening absorption and secretory activity Deconjugation of bile salts (bile salts not reabsorbed) lipid absorption membrane secretion and steatorrhea Inhibition of pancreatic enzymes b’down and abs of nutrients malabsorption Malabsorption of vit (fat & water soluble), Fe and Amino acids predisposes to anaemia Folate deficiency exacerbate villous atrophy (may need to give supplements) Malabsorption nutrients dumped into lumen bacterial fermentation + osmotic overload diarrhoea Pathogenesis and epidemiology is almost identical with Cryptosporidiosis Life Cycle: Ingested cysts trophozoites (EXcystation) when exposed to stomach acid and intestinal proteases After excystation undergoes binary fission within 30minutes Trophozoite cyst (ENcystatin) occurs at alkaline pH and changes in bile salt concentrations Cysts passed into stool Clinical Presentation (1-3 wk incubation) Often asymptomatic (but are still infective) Explosive, watery, malodorous stools, cramps, nausea, epigastric pain, mild fever Diarrhoea can be acute (usually 3-4 days, <1 month) or Chronic diarrhoea (month to years) and malabsorption (in 50% of chronic cases) Brief recurrent episodes of foul, frothy stools Steatorrhea (fatty diarrhoea) ↓ growth, failure to thrive, weight loss Blood and mucus usually NOT present Infection leads to development of antibodies against Giardia. However organism in intestinal lumen not eaten by phagocytes. Antibodies may neutralise toxin severity Investigations Diagnosis of intestinal parasites is usually by identifying characteristic trophozoites/worms or cysts/eggs in stool In giardiasis, parasite numbers in stool may be low and esp. hard to find in chronic cases Aspiration and biopsy possible but stool examine is preferred (3 stools should be taken at 2 day intervals) ELISA test also available OR else just TREAT and see. Stool sample are almost NEVER cultured Treatment Scrupulous hygiene (↓faecal-oral re-infection/transmission) Oral rehydration with all diarrhoea Metronidazole is drug of choice – 400mg TDS 1/52 (Works by interfering with DNA synthesis) Tinidazole is actually the recommended 1st line therapy in AMH (2000mg single dose) Health promotion and education aimed at improving personal hygiene, and emphasizing hand washing, sanitation and food handling, are effective control activities for the reduction of person-toperson transmission. Week 7: Peptic Ulcer & Helicobacter pylori Definitions & Epidemiology Ulcer: (Histologically) a breach in the mucosa of the alimentary tract that extends through the muscularis mucosa, into the submucosa or deeper. Helicobacter pylori: A spiral shaped, gram negative, urease producing bacterium. Its ability to colonise in the acidic stomach env is DT sheathed flagella that allow rapid movement to mucus layer where pH is higher, and its ability to produce urease - converts urea to ammonia, the pH directly around th colony. Peptic ulcer: is a chronic, often solitary lesion that occurs in any portion of the GIT exposed to the action of acid/peptic juices. There is a high prevalence of H.pylori in developing countries and is ass with SES worldwide. Spread is oral-oral or faecal-oral route. Pathogenesis Peptic ulcers are produced by an imbalance between gastroduodenal mucosa defence mechanisms and the damaging forces, particularly gastric acid and pepsin. H.pylori infection is a major contributing factor to peptic ulcer. H.pylori mechanisms of evil action: H.pylori Infection intense inflamm & immune response production of anti-inflam cytokines IL1,6,8 & TNF Recruitment neutrophils activation T & B cells H.pylori infection enhanced gastic acid secertion & impaires bicarb procution by duodenum Decrease in luminal pH of duodenum H.pylori infection bacteria secretes Urease Urea B’down to toxic compounds (including Ammonia) Damage to mucus lining and surface epithelial cells Morphology Peptic ulcers are usually solitary lesions of 4cm in diameter with 98% located in either the 1st protion of the duodenum and the antrum of the stomach (Duo:Stom = 4:1). Clinical Features Epigastic gnawing, burning or aching px Px tends to be worse @ night and occ usually 1-3 hrs post meals during the day Px is relieved with alkalis or food In perforating ulcers Px may be referred to the back, left upper quadrant or chest (often misinterpreted as cardiac in origin!!) May initially present with complications of anaemia, frank haem or perforation Investigations Non-invasive methods: C13 Urea Breath Test – Quick and easy way to detect presence of H.pylori. Measurement of 13CO2 in after ingestion of C13 urea Serology Tests – IgG antibodies Stool Test Invasive (Endoscopy) Rapid Urease Test – gastric biopsy tested for urease Culture and Histology of gastric biopsy Treatement 1. Neutralise acid secretion – Antacids (AlOH, MgOH, CaCO3) 2. Inhibit acid secretion – PPIs (Pantoprazole), Arachidonic acid agonists (Misoprostol), Histamine receptor antagonists (Ranitadine) 3. Protect mucosa from damage – Bismuth subcitrate / Sucralfate 4. Eradicate causiative agent (H.pylori) – Multi antibiotics PPI + Clarithromycin + Amoxycillin PPI + Clarithromycin + Metronidazole PPI + Amoxycillin + Metronidazole PPI + Metronidazole + Tetracycline + Bismuth 7 days > 90% success 7 days > 80% success 7 days 80-90% success 7 days 75% success 1st Line RX: Resistance to Clarithromycin 1st Line RX: when Amox unsutible. Metron has resistance 1st Line RX: When Clariethro not suitable Complicate regimen, poorly tolerated. Use only if 1st line fail Week 8: Glycogen Storage Disease Definition & Epidemiology A disease resulting from a hereditary deficiency of one of the enzymes involved in the synthesis or sequential degradation of glycogen. Depending on the tissue or organ distribution of the specific enzyme in the normal state, glycogen storage in these disorders may be limited to a few tissues or be more widespread. Pathogenesis & Morphology Based on pathophysiology, the disorders are broken into 2 groups: 1. Hepatic forms – The liver contains enzymes that synthesise glycogen for storage and ultimately break it down into free glucose for release into blood. A deficenncy in hepatic enzymes involved with gylcogen metabolism causing not only storage problems but also low BGL. Eg) Von Gierk Dz (glucose-6-phosphatase deficiency - PBL). 2. Myopathic forms – in striated muscles glycogen is used as a source of energy. Energy is derived from glycolysis with ultimately leads to the production of lactate. If enzymes that fuel the glycolytic pathway are insufficient then glycogen storage occ within the muscles and causes muscle weakness DT impaired energy production. Pts present with muscle cramps post exercise and failure to lactate levels with activity. Treatment Monitor BGL, Corn Starch?? Type Affected tissue Liver glycogenoses I (Von Liver, intestine, Gierke) kidney (25%) Enzyme defect Clinical features Tissue nec for Dx Outcome Glucose-6phosphatase Liver DNA testing III (Forbes) (24%) Liver, muscle (abnormal glycogen structure) Liver (abnormal glycogen structure) Glycogen debranching enzyme Hepatomegaly, ketotic hypoglycaemia, stunted growth, obesity, hypotonia Like type I Leucocytes, liver, muscle Liver Liver phosphorylase /phosphorylase kinase Phosphorylase 6 kinase deficiency Failure to thrive, hepatomegaly, cirrhosis and its complications Hepatomegaly with hypoglycaemia in childhood If pts survive initial hypoglycaemia, prognosis is good; hyperuricaemia is late complication Good prognosis but progressive neuropathy and cardiomyopathy Death in first 5 years Liver transplantation Liver Good Hepatomegaly, hypoglycaemic fatiguability Liver, muscle No treatment Heart failure, cardiomyopathy Fibroblasts, muscles Death in first 6 months Muscle cramps and myoglobinuria after exercise (in adults) muscles Normal life-span; give sucrose prior to exercise IV (Anderson) (3%) VI (Hers) (VI and VIII = 30%) VIII Liver Branching enzyme Leucocytes, liver, muscle Muscle glycogenoses II (Pompé) (15%) Liver, muscle, heart V (McArdle) Muscle only Lysosomal acid αglucosidase Phosphorylase Week 9: Anorexia Nervosa “You can never be too rich or too thin.” - Duchess of Windsor (1896-1986) Epidemiology AN is 10 times more common in females. The most common age of onset is 14-18 years, but AN has been reported in girls as young as 8 years. It is believed to be more common in the SES. Pathogenesis - Socio-cultural factors are described as forming “the modern cult of thinness” in Western societies. Evidence indicates a culture bound syndrome, as AN is rare in Asia and developing countries. - Adverse life events my precipitate AN. Severe life events are found in the majority of patients with onset after 25 years, and a minority of those with onset before 25 years. - Personality disorder is found in at least 70% of those with AN. OCD most common. Assessment and Presentation The patient is usually a teenage female, brought in by her parents. There has been weight loss, cessation of the menses, fine hair growth on the face and limbs, refusal to eat in the manner expected for her age and family circumstances, particular avoidance of CHO and fatty foods, frequent weighing, often vomiting and excessive laxative use, insomnia, irritability, sensitivity to cold, withdrawal from friends. Anorexia Nervosa DSM-IV Diagnostic criteria A. Refusal to maintain body weight at or above a minimally normal weight for age and height (e.g., weight loss leading to maintenance of a body weight less than 85% of that expected) B. Intense fear of gaining weight or becoming fat, even though underweight. C. Distorted body image. D. In postmenarche females, amenorrhea (the absence of at least three consecutive menstrual cycles). Bulimia Nervosa DSM-IV Diagnostic criteria A. Recurrent episodes of binge eating. An episode of binge eating is characterized by both: 1. eating, in a discrete period of time and amount of food that is definitely larger than most people would eat during the same time and in the same circumstances 2. a sense of lack of control over eating during the episode. B. Recurrent inappropriate compensatory behaviour in order to prevent weight gain, such as selfinduced vomiting; misuse of laxatives, diuretics, enemas, or other medications, fasting, or excessive exercise. C. The binge eating and inappropriate compensatory behaviour both occur, on average, at least twice a week for 3 months. D. Self-evaluation is unduly influenced by body shape and weight. E. The disturbance does not occur exclusively during episodes of Anorexia nervosa. Possible admission criteria (to be discussed with Adolescent Medicine consultant) 1. Physical ( for nasogastric resuscitation ) * Dehydration * Postural hypotension (fall in systolic BP lying to standing > 20mmHg), bradycardia * Hypothermia (temp. <35o C oral) * Electrolyte abnormalities (eg. hypokalaemia, hypernatraemia) * Severe weight loss (>30% of pre-morbid weight) Investigations: * Urea and electrolytes, creatinine * Urinalysis - including pH (possibility of diuretic use ) * ECG (if K+ abnormal) A medical admission for resuscitation would usually result in a 4 week period of inpatient treatment. 2. Psychiatric Patients with anorexia nervosa may be at risk of suicide or other at-risk behavior (eg. acute bulimic phase). These patients require urgent psychiatric assessment. On consultation with the adolescent consultant and the adolescent psychiatry team, admission may be considered. The admission is usually of shorter duration than if the patient were physically comprised. Outcome The annual mortality rate is 0.6%. Full recovery includes return to appropriate weight and continued growth and development, restoration of menstruation, and normal eating behaviour and attitude with regard to food and body shape. Treatment Inpatient treatment restores weight most rapidly (usually within three months). There may be difficulty in persuading the patient to remain in an inpatient program. Benefits include the omnipresence of skilled nursing staff, able to provide psychotherapy and supervision. The patient is encouraged to take nutritious meals atregular meal times. Family therapy is usually offered and is effective in helping to correct miscommunication and misunderstandings within the family, and restore healthy eating habits (especially for pts < 19 years). Drug treatment usually provides little benefit. Chlorpromazine or olanzapine may reduce distress and stimulate the appetite. Antidepressants may be indicated for the treatment of major depression, but they are ineffective in the presence of malnutrition. Compulsory treatment and naso-gastric feeding depend on the provisions of local mental health legislation. They are generally avoided as they are disruptive to the trusting patient-doctor relationship and acceptance by the patient of responsibility for her actions. However, they become necessary should malnutrition pose an immediate threat to life. Follow-up All patients with eating disorders require close and expert monitoring and long-term therapy. This usually involves a combination of adolescent medicine and psychiatry out-patient support.