Clinical Pathology

Historically only imaging, biopsy & predictive scores Novel biochemical markers - ELF score -PIIINP -TIMP-1 -Hyaluronic acid

Biochemical markers of fibrosis in the liver

High ALP High Ca Normal phosphate Low PTH

Biochemistry of bone mets

High alkaline phosphatase High calcium Low phosphate High parathyroid hormone

Biochemistry of hyperparathyroidism

Platelet transfusion in the prevention of bleeding

Bone marrow failure: platelet count <10 × 109/L or <20 × 109/L if additional risk, e.g. sepsis Prophylaxis for surgery more major surgeries <50 x 109/L CNS or eye surgery <100 x 109/L

destruction of normal bone (osteoclasts) Breast/lung Kidney/thyroid

Bone metastases is common in several malignancies, what is lytic bone metastases?

• T cell dependent • Animal models • T cell immunosuppression • Directed against foreign HLA molecules • Effect of HLA mismatch • Typically 7- 10 days after transplant

Acute cellular rejection

Which pathogens are transmitted to baby by the haematogenous route?

(by blood) Cytomegalovirus Parvovirus B19 Toxoplasmosis Syphilis Varicella Zoster virus Rubella Zika virus

Eosinophils

A type of white blood cell (granulocyte) with low phagocytic activity that is thought to play a role in defense against parasitic worms by releasing enzymes toxic to these invaders.

o Full thickness coagulative necrosis of mucosa or deeper layers (deeper layers of the stomach or duodenum, sometimes into the muscle, formation of granulation tissue and then fibrosis over time) o Covered with ulcer slough: necrotic debris + fibrin + neutrophils o Granulation tissue at ulcer floor

Acute gastric ulcer histology

Acidic damage to the stomach mucosa • Usually due to chemical injury o Drugs e.g. NSAIDS o Alcohol o Initial response to helicobacter pylori infection • Effects depend on severity of the injury: erosions and haemorrhage • Generally, heal quickly

Acute gastritis

Other vulval tumours: malignant melanoma

- 5% vulval cancers - mean age: 50-60 - local recurrence in third, spread to urethra frequent - lymph node/ haematogenous (blood) spread common - depth of invasion correlates with LN involvement - can be heavily pigmented - rarely have no pigment at all = amelanotic melanoma - most important prognostic factor = depth of invasion = Breslow thickness/ depth o thickness and depth: staging of melanoma = Breslow!

Other vulval tumours: Paget's disease: extramammary

- 5% vulval cancers, mean age 80 - primary: from the vulval area: sweat glands etc. - spreads across the basal membrane - secondary carcinoma: invade, through tissue, not basal layers - pruritis/ burning/ eczematous patch - in situ adenocarcinoma of squamous mucosa - often recurs following excision - can develop into invasive adenocarcinoma - usually no underlying tumour, not mammary disease - 5% regional malignant disease - Paget's disease often looks like eczema - abnormal pale malignant cells within the epidermis - Paget's disease of the nipple, breast = ductal carcinoma in situ spreading into epidermis - Vulva: no underlying tumour: believe the glandular malignant cells arise in the intra-epidermal portion of sweat ducts o Bladder o Cervix o Exclude primary rectal carcinoma if perianal component

Dose of platelets given in a transfusion

"Adult therapeutic dose" is a pool of 4-6 donations or a single apheresis donation Platelet count per dose : 3x10^11 Expect to raise platelets by 20-60x10^9/L

Early malignant mesothelioma

(IN DARK BLUE) A small tumour can produce a large pleural effusion The tumour can be difficult to identify on imaging and therefore it is difficult to target biopsies at it Malignant cells may be shed into the effusion therefore effusion cytology may allow an early tissue diagnosis to be made

Causative organisms of puerperal endometritis

- E. coli - beta-haemolytic streptococci - anaerobes

Cervical carcinoma spread and prognosis

- FIGO staging o I: confined to cervix o II: invades beyond uterus, not to pelvic side wall o III: extends to pelvic wall, lower third vagina, hydronephrosis o IV: invades bladder/ rectum/ outside pelvis - Metastasis o Predictable: pelvic and para-aortic lymph nodes o Via blood to lungs, bone etc - Local invasion, extending out of the cervix to bladder, ureters and rectum = primary surgical treatment inappropriate - Lymphatic metastasis: tumour spreads to local lymph nodes = dictates treatment

Bronchioloitis

- Inflammation of the bronchioles -caused by viruses such as RSV - seen in young children with the incidence peaking at 6 months of age - often start as a viral illness and progresses to wheezing, cough, dyspnea and cyanosis -a seasonal viral illness characterized by fever, nasal discharge, and dry, wheezy cough. On examination there are fine inspiratory crackles and/or high-pitched expiratory wheeze"

Immunological complications of transfusion

Acute haemolytic transfusion reaction due to incompatibility Delayed haemolytic reaction Post transfusion purpura Allergic /anaphylactic reaction TRALI (Transfusion-related acute lung injury) Transfusion-associated graft-versus-host disease (TA-GvHD) Acute reactions present more than 24 hours post transfusion Delayed reactions present less than 24 hours post transfusion

What complications can infections cause in pregnancy?

- miscarriage - congenital anomalies - fetal hydrops - fetal death - preterm delivery - preterm rupture of the membranes -Abortion -Stillbirth child -Prematurity -IUGR -Congenital malformations Maternal anitbodies cross the placenta and give passive immunity to the fetus

Vulval sqaumous cell carcinoma

- most common vulval cancer: 90% - associated with VIN o age <60 o associated with lower genital tract neoplasia: CIN o HPV positive - Associated with inflammatory dermatoses o Age >70 o Lichen sclerosus - 15% risk of malignancy: symptomatic lichen sclerosus o Lichen planus - Associated with VIN - Associated with inflammatory dermatoses - Eroded plaque/ ulcer - Spreads locally to involve: o Vagina and distal urethra o Ipsilateral inguinal LNs o Contralateral inguinal LNs, deep iliofemoral LNs: 25% if inguinal nodes positive - Risk of lymph node metastases o <1mm depth of invasion: LN metastases very rare = wide local excision o 1-3mm: 10% o >4mm: 40% - for 1-3mm and >4mm: lymph node sampling: groin node dissection/ sentinel node biopsy

Glandular parenchyma (breast tissue)

-same bilaterally on breasts -increase in density with hormone increases and pregnancy (lighter on ultrasound) -decrease in density with increased age (darker on ultrasound) -atrophy in menopause 15-20 lobes in the breast Drained by a lactiferous duct All lobes converge toward the aerola Near the aerola, the lactiferous duct dilated to form the lactiferous sinus

1 unit of fresh frozen plasma (FFP) dose

1 unit of fresh frozen plasma contains all clotting factors at physiological levels Therapeutic dose: 12-15 ml/kg (4-6 units for average adult)

• intermediate severity: confluent necrosis of adjacent hepatocytes in a bridge between a portal tract and hepatic vein • patient transplanted for acute liver failure, all degrees of liver injury can be seen in diff areas of the liver: o acute hepatitis o severe acute hepatitis with confluent necrosis o acute hepatitis with bridging necrosis

Acute hepatitis with bridging necrosis

o Benign non-functional nodules of adrenal cortex. o Between 1.5 and 3% of population. Higher in elderly, hypotensive and diabetic patients. o No clinical symptoms. Incidental discovery on radiographic studies. o No treatment required

Adrenal cortical nodule

Germ cell tumours

15-20% all ovarian tumours Germinomatous Dysgerminomas (differentiation - oogonia, malignant, chemosensitive) Non-germinomatous Teratomas (differentiation towards multiple germ layers) Most mature (benign; 1% malignant transformation) Yolk sac tumours (differentiation towards extraembryonic yolk sac, malignant, chemosensitive) Choriocarcinomas (differentiation - placenta, malignant, often unresponsive) Rx: surgical +/- chemo-/radiotherapy

PTH acts on the bone to drive causes resoprtion of bone (via osteoclasts) to release Ca and PO4 PTH acts on the kidneys to increase reabsorption of Ca from the filtrate but increase excretion of PO4

2 direct actions of parathyroid hormone

Ear: Acute otitis media Otitis externa

2 examples of ear infections

Pharyngitis Diptheria

2 examples of throat infections

To improve the outcome To provide epidemiological data

2 reasons to carry out a diagnostic test:

Phaeochromocytoma (adults) Neuroblastoma (children)

2 types of adrenal medullary tumours

Gram negative rods like E.Coli Gram positive cocci like Enterococcus spp and staphylococcus saprophyticus (latter is most likely to affect young women with cystitis)

2 types of bacteria which can cause UTI

intestinal type diffuse type

2 types of gastric cancer when looking down a microscope

Pattern recognition receptor Function

2 types of immunodeficiency in phagocytes

Vesicular or non-vesicular

2 types of rashes

spontaneous mutation and natural selection

2 ways bacteria develop antibiotic resistance

Epidemiology of malignant mesothelioma

2727 new UK cases in 2014 1.5% of cancer deaths 2567 UK deaths in 2014, 83% were males 17th commonest fatal cancer

Ovarian cancer in brief

2nd commonest gynae cancer; >7,100 women >4,300 deaths/yr UK; 80% >50's; 80-90% epithelial Risk factors: FH, ↑age, PMH breast cancer, smoking, E2-only HRT, Lynch II syndrome, obesity, nulliparity Protective factors: Oral Contraceptive Pill, breastfeeding, hysterectomy Hx: non-specific symptoms; pain, bloating, weight loss, PV bleeding, urinary frequency, anorexia FIGO Staging: 1 - 4 Rx: Stage <1C epithelial tumours -->TAH/BSO, omentectomy, appendectomy, lymphadenectomy & adjuvant chemo - chemo only in sensitive GCTs Prognosis: Overall 5 years 43% survival

o transient/ evanescent: >80%: lasts for hrs, few days and then gets better o chronic segmental ulcerating: ischaemic stricture o acute fulminant and gangrenous: 10-20%: severe, complete necrosis, infarction of the bowel wall, surgical emergency

3 clinical forms of ischaemic colitis

Phase 1: shock Phase 2: catabolic state Phase 3: anabolic state

3 phases after trauma

• Acute antibody mediated rejection • Acute cellular rejection • Chronic antibody mediated rejection

3 types of clinical rejection in kidney transplant

1) Classical model—the steroid hormone dissociates from its plasma carrier protein and diffuses across the cell membrane. After gaining entry to the cell, the free hormone binds to an intracellular receptor and alters gene transcription 2) Receptor mediated endocytosis—the steroid hormone, bound to its plasma carrier protein is brought into the cell via a cell surface receptor. - The complex is broken down inside the lysosome - The free steroid hormone diffuses into the cell where it subsequently exerts its action at the genomic level or undergoes metabolism 3) o Signalling through cell-surface receptors The free steroid hormone alters intracellular signalling by binding to cell surface receptors The steroid hormone could exert these effects directly or could alter signalling by blocking the actions of peptide hormones

3 ways a steroid hormone can interact with a cell

Lower respiratory tract infections in children

30-40 cases per 1000 children per year in the UK; (a GP will see, on average, 1-2 cases per year) Prevalence : Every year, pneumonia contributes to 750,000 - 1.2 million neonatal deaths worldwide Includes pneumonia, acute bronchitis & bronchiolitis Respiratory viruses remain the leading cause in children under 5years

Behaviour of vulval intraepithelial neoplasia

35-50% recur Positive margins predict recurrence Progression to invasive carcinoma in 4-7% of treated women and up to 87% of those untreated. Invasion more likely to occur in postmenopausal/immunocompromised Spontaneous regression may occur particularly in young, postpartum women

Squamous cell carcinoma 20-30% Small cell carcinoma 15-20% Adenocarcinoma 30-40% Large cell undifferentiated carcinoma 10-15%

4 major types of primary lung carcinomas

1. Heat (calor) 2. Redness (rubor) 3. Swelling (tumor) 4. Pain (dolor) 5. Loss of function (function laesa)

5 cardinal signs of acute inflammation

1) Basal layer=stratum basale 2) Prickle cell layer=Stratum spinosum 3) Granular layer=stratum granulosum 4) Stratum lucidum=only presnt in skin of the sole of the foot 5) Keratin layer=stratum corneum

5 layers of epidermis in thick skin

o Before patient contact o Before aseptic task o After body fluid exposure risk o After patient contact o After contact with patient surroundings

5 moments of hand hygiene at the point of care

Define ovarian neoplasms

90% epithelial and based on cell type; benign cystadenoma-->borderline-->malignant cystadenocarcinoma progression; germ cell tumours; sex cord stromal tumours; metastatic tumours

Cervical intraepithelial neoplasia

A change in the cells on the surface of the cervix that may signal early beginnings of cervical cancer; sometimes referred to as cervical dysplasia. Pre-invasive stage of cervical SCC Detection of CIN is the aim of the cervical screening programme Graded according to increasing abnormality

Basophils

A circulating leukocyte that produces histamine Type of granulocyte which is rare and forms part of the primitive immune system

Urine sampling

A clean catch sample should be obtained If not possible, use non invasive method i.e. Urine collection pad Do not use cotton wool balls, gauze or sanitary towels. If non invasive method not possible Use catheter sample or suprapubic aspiration

methotrexate

A commonly used cytotoxic drug that is a folate antagonist?

Fibrocystic disease

A constellation of benign, hormonally mediated breast changes including cyst formation, stromal fibrosis and mild epithelial hyperplasia without atypia. C/F : Lumpy, premenstrually painful breasts. FCC symptomatology generally ceases 1-2 yrs following menopause

cyclophosphamide

A cytotoxic drug that commonly causes cystitis?

How was asbestos used?

A fire-proof material widely used in commercial and domestic buildings and in shipbuilding from the 1940s to the 1990s Between 1940 and 1998 there were 5.5 million tons of asbestos imported into the UK Crocidolite and amosite imports were banned in 1985 and all asbestos imports were banned in 1999 Some has sailed away in ships but a lot is still here in buildings presenting a risk to those working in or being near building maintenance and demolition processes

Has metal/plastic construction Fragile, sensitive parts Decontaminated chemically using several alternative agents and is delivered via the washer disinfector

A flexible endoscope has a high risk of infection, how is it decontaminated?

Direct (one host) Simple indirect Complex indirect

A life cycle is either:

Malignant mesothelioma

A neoplasm of the mesothelial cells that line serous cavities - pleura, peritoneum, pericardium, tunica vaginalis 92% are pleural, 8% are peritoneal Both are commoner in men Peritoneal mesotheliomas affect a higher proportion of women, have a higher proportion of low grade type and are less strongly associated with asbestos dust exposure Tend not to metastasise widely

What is the normal mesothelium that makes up the pleura?

A single layer of mesothelial cells lines the pleural cavity They secrete hyaluronic acid rich mucinous pleural fluid that lubricates the movement of the visceral and parietal pleura against each other during respiration

o Plastic/metal construction o Paper packaging o Should be decontaminated by sterilisation o γ-irradiation pre-use o Disposal after use

A syringe needle has a high risk of infection, how is it decontaminated?

As with any unwell or septic patient... A = Airway ensure an open, patent and maintained airway B = Breathing Assess respiratory rate and saturations Provide supplemental oxygen to reach prescribed target C = Circulation Assess blood pressure and heart rate Gain IV access and give IV fluids if haemodynamically unstable Urinary catheter to monitor urine output

ABC

o Active immunity is usually long-lasting immunity produced by the immune system in response to antigens. o These antigens can be from natural infection or from vaccination. o The immune system makes antibodies to help destroy antigens. o The benefit of vaccination is that active immunity occurs without disease or disease complications. o The persistence of protection for many years after natural infection or vaccination is called "immunologic memory."

Active immunity

• dsDNA. • Chromatin. • Ribosomal protein. • SS-A (52 and 60). • SS-B. • Sm. • Sm/RNP. • RNP (A and 68). • Scl-70. • Jo-1. • Centromere B.

ANA screen uses a microbead-based immunoassay:

Open pneumothorax

An open or penetrating chest wall wound, usually traumatic, through which air passes during inspiration and expiration, creating a sucking sound; also referred to as a sucking chest wound. External air is drawn into the pleural cavity during inspiration, reducing potential lung expansion

• Acute o Diverticulitis/ peridiverticular abscess: 20-25% o Perforation o Haemorrhage: 5% (erode an artery or vein = bleeding, passing PR) - Artery becomes ulcerated-->haemorrhage-->bleeding through anus • Chronic o Intestinal obstruction: strictures: 5-10% o Fistula: urinary bladder, vagina i.e. faecal material can come from vagina in a fistula o Diverticular colitis: segmental and granulomatous can present with diarrhoea and bleeding o Polypoid prolapsing mucosal folds

Acute and chronic complications of diverticlar disease

anti-inflammatory • Decreased neutrophil margination • Reduced production of inflammatory cytokines • Inhibition phospholipase A2 (reduced arachidonic acid metabolites production) • Lymphopenia (lower levels of lymphocytes) • Decreased T cells proliferation • Reduced immunoglobulins production

Action of corticosteroids

o Increase secretion of insulin and growth hormone o Reduces intestinal motility and gastric acid secretion o Increase glucose levels o Glycogenolysis o Gluconeogenesis o Lipolysis o

Actions of glucagon

Diffuse alveolar damage - exudate & death of type I pneumocytes form hyaline membranes lining alveoli followed by type II pneumocyte hyperplasia. Histologically acute interstitial pneumonia Adult respiratory distress syndrome (shock lung) - shock, trauma, infections, smoke, toxic gases, oxygen, paraquat, narcotics, radiation, aspiration, DIC

Acute interstitial lung disease

- Presents with a sudden onset of pain in the gingiva, and the tissue appears eroded with superficial grayish pseudomembranes - Other manifestations include halitosis, altered taste sensation, fever, malaise, and lymphadenopathy - Requires antibiotics

Acute necrotising ulcerative gingivitis (Vincent's angina)

Rapid onset Characterised by: Widespread necrotising process extending the length of the posterior mediastinum and retropertioneal space sometimes Rupture of mediastinal abscess into the pleural cavity with empyema or development of loculations (fibrous scar tissue in pleural cavity) Pleural or pericardial effusion, frequently with tamponade Mortality of acute necrotising fascicitis is high even when appropriate antibiotics are administered

Acute nectorising mediastintius in adults

Acute OE range in severity mild/moderate/severe + necrotising (malignant) OE Typically unilateral 90% AOE bacterial (most common: Pseudomonas aeruginosa & Staphylococcus aureus) 2% AOE fungal Diagnosis: history & otoscopic examination Investigations: Ear swab or pus sample for culture. For necrotising otitis externa: CT temporal bone (and bone biopsy). Blood cultures (if systemically unwell).

Acute otitits externa

• relatively common: 10-20 per 100,000 in Western Countries • Gallstones: 50% cases • Alcohol: 25% cases • Rare causes: <5% o Vascular insufficiency o Viral infections: mumps, coxsackie B o Hypercalcaemia o ERCP o Inherited causes • Idiopathic: 10% • Alcohol and gallstones account for up to 80% cases • Acute pancreatitis: 35-60% have gallstones, 5% patients with gallstones have pancreatitis • Male: female ratio varies with cause: 1M: 3F in biliary disease, 6M: 1F alcoholism

Acute pancreatitis

• Usually presents as an emergency requiring admission to hospital • Sudden onset of severe abdo pain radiating to back • Nausea and vomiting • May be mild (recovery within 5-7days) but can be serious with high mortality • Raised serum amylase/ lipase (>3x normal) • Persistent hypocalcaemia is a poor prognostic sign • Full blown pancreatitis is a medical emergency: present as acute abdomen

Acute pancreatitis clinical features

• Acute necrotising liquefaction • Inflammatory • Aetiology o Gallstones o Alcohol o Drugs o Hypertiglyceridaemia o Trauma, infectious o Rare tumours, autoimmune, Scorpion Toxins!

Acute pancreatitis-what is it? Aetiology

• Pharyngitis: inflammation of the back of the throat (pharynx), resulting sore throat & fever • Acute tonsillar pharyngitis: symmetrically inflamed tonsils and pharynx (+/- fever +/- headache) (Severe infection: patient has marked systemic symptoms of infection and/or unable to swallow). • Consider infectious mononucleosis (EBV): symmetrically inflamed tonsils / soft palate inflammation and posterior cervical lymphadenopathy • Suspect epiglottitis: sudden onset of severe sore throat, no inflammation of the tonsils and/or oropharynx & systemic symptoms/signs of infection

Acute sore throat causes

Throat swab for culture, blood cultures (Blood tests: full blood count, urea and electrolytes and liver function tests) Suspected infectious mononucleosis: blood sample for monospot or EBV serology

Acute sore throat--inpatients investigation

This investigation is done for non-severe infection No routine investigations, unless infectious mononucleosis is suspected

Acute sore throat--outpatient/ambulatory investigation

o Non mumps o Occurs in patients with poor oral hygiene and dehydration o Almost always caused by Staphylococcus aureus o Normally one side affected o Sudden onset of swelling from cheek to angle of the jaw and bacteraemia = patient systemically unwell o Treatment: surgical drainage, antibiotics administered

Acute supprurative parotitis

• Learned responses in immune organs. • T cells and B cells. • Highly specific - T and B cell receptors. • Strong memory and amplification component (e.g. vaccines, previous infection). • Many regulatory mechanisms. • Slow response - days-weeks for initial exposure. • Responses may last months-years. • Adaptive immunity requires cells of the innate immune system too: • Innate Adaptive - Dendritic cells present antigen to T cells. • Adaptive Innate - T cell cytokines and B cell antibodies activate innate cells to cause inflammation.

Adaptive immunity

a condition that occurs when the adrenal glands do not produce enough cortisol or aldosterone o Primary adrenal cortical insufficiency caused by adrenal dysgenesis, adrenal destruction, autoimmune adrenalitis, TB. o Secondary due to failure of ACTH secretion o 5.3 per million population. o High mortality if not diagnosed. o Autoimmune form is most common. o Triad of hyperpigmentation, postural hypotension and hyponatraemia. o Treatment with long term steroid replacement. o If undiagnosed can prove fatal.

Addison's disease

a malignant tumor that originates in glandular tissue • Incidence has risen dramatically in industrialised countries due to increase in obesity leading to gastroesophageal reflux • Mainly lower oesophagus • Higher incidence in main: male/female ratio: 7:1 • Higher incidence among Caucasians • Aetiology: o Barrett's oesophagus: most originate from this o Tobacco o Obesity

Adenocarcinoma

Bile duct adenoma/ von Meyenberg complex A benign proliferation of bile duct cells Tiny white nodules Look like metastases grossly - do a frozen section and we can tell you if they are benign or malignant

Adenoma of bile ducts

benign tumors of glandular epithelial origin • If they have finger like projections—villous • Flat and have finger like projections—tubulo-villous • Smooth--tubular • Commonly polypoid but may be flat • Precursor of colorectal cancer: at least 80% • Present in 25-35% population >50yrs • Multiple in 20-30% patients • Evenly distributed around colon but larger in recto-sigmoid and caecum • Macroscopic appearance: pedunculated sessile or flat • Architectural type: villous, tubule-villous or tubular - using microscope • Histological grade: high vs low grade dysplasia: risk of it becoming malignant • The adenoma: carcinoma stage: a small % of adenomas progress to adenocarcinoma over 10-15yrs o 80% of large bowel cancers start off as adenomas

Adenomas

the process of transferring a form of specific immune response from a donor to a recipient This can occur through: • Stem cell transplant (SCT) • Uses: o Immunodeficiencies (SCID) o Lymphomas and leukemias o Inherited metabolic disorders (osteoporosis) o Autoimmune diseases

Adoptive immunotherapy

o Benign neoplastic proliferation of adrenal cortical tissue. o Incidence from 1-5% of population. o Symptoms related to endocrine hyperfunction (hypertension, Cushing's symptoms and virilisation). o Aldosterone-producing tumours cause Conn's syndrome. Cortisol-producing tumours cause Cushing's syndrome. Rare tumours cause virilisation.

Adrenal cortical adenoma

o Malignant counterpart of adrenal cortical adenoma. o 3% of endocrine neoplasms. About 1 per million of population. o Symptoms related to hormone excess. o Abdominal mass. o Prognosis, age and stage dependent. o 5 year survival about 70%.

Adrenal cortical carcinoma

Widely used: o Specific due to antibody specificity o Sensitive - able to measure picomolar concentrations o Amenable to automation o 2 main types in use in clinical chemistry o Immunometric assays

Advantages of immunoassay

o Environmental triggers, allergens e.g. dust mite o NSAIDs, cold air, exercise, infections, emotion, ABPA (aspergillus)

Aetiology of Asthma i.e. what causes narrowing of the bronchial tree

TOXIC: alcohol, cigarette smoke, drugs, hypercalcaemia, hyperparathyroidism infections IDIOPATHIC GENETIC CFTR: cystic fibrosis gene, PRSS1, SPINK1 mutations AUTOIMMUNE AND ALCOHOL RECURRENT ACUTE PANCREATITIS OBSTRUCTION OF MAIN DUCT: due to cancer, scarring o Excluding CF: 90-95% cases due to alcohol/ idiopathic o Less than 10% of alcoholics develop the disease o Cig smoking = strong independent risk factor for pancreatitis o No agreement how these diverse factors to chronic pancreatitis

Aetiology of chronic pancreatitis (TIGARO)

o Diet (smoked/cured meat or fish, pickled vegetables) (Asian mainly) o Helicobacter pylori infection (Western mainly) o Bile reflux (e.g. post Billroth II operation) o Hypochlorhydria--LOW HCl (lack of HCl allows bacterial growth)

Aetiology of gastric adenocarcinoma

o Lifestyle is linked to 75% of gastric cancers - Diet: smoked/ cured meat or fish, pickled vegetables - Smoking and alcohol - Overweight or obese o Helicobacter pylori infection: implicated in 30% of gastric cancer o Bile reflux/ low levels of stomach acid o 1% hereditary

Aetiology of gastric cancer

Tobacco smoking Occupational/Industrial hazards, eg Asbestos, uranium, arsenic, nickel Radiation - mines in which there is radon - Survivors of the atomic bomb in Japan after 2nd world war had a high incidence of lung cancer Lung fibrosis - old terminology 'scar cancers' has been challenged - increase risk of lung cancer in patients with pulmonary. fibrosis Genetic mutations - EGFR, KRAS, ALK etc - usually seen lung cancers in never smokers

Aetiology of lung cancer

Intra-amniotic infections

Affects 1-2% term pregnancies Affects 20-25% pregnancies with pre-term labour major cause of perinatal morbidity and mortality "Chorioamnionitis" refers to inflammation of umbilical cord, amniotic membranes/fluid, placenta

o Prevent deaths o Prevent infection o Prevent transmission (secondary cases) o Prevent clinical cases o Prevent cases in a certain age group - To reduce morbidity and mortality from vaccine preventable infections

Aim of immunisation

pneumothorax

Air in the pleural cavity, which leads to a collapsed lung

Alcohol is the major cause of liver disease • Spectrum of fatty change, alcohol steatohepatitis, cirrhosis • Depends on dose and susceptibility • Death from liver disease has risen by a quarter in 8yrs due to alcohol and obesity • Many patients with metabolic syndrome: obesity, T2DM, have a similar pathology of liver disease = NAFLD = non-alcoholic fatty liver disease • Combination of risk factors of alcohol and obesity = synergistic • Lifestyle factors account for the big increase in deaths from liver disease

Alcohol and the liver

• Indications: o Allergic rhinoconjutivitis not controlled on maximum medical therapy o Anaphylaxis to insect venoms • Mechanisms: o Switching of immune response from Th2 (allergic) to Th1 (non-allergic) o Development of T reg cells and tolerance • Routes: o Subcutaneous or sublingual for aero-allergens • Side-effects: o Localised and systemic allergic reactions

Allergen specific immunotherapy

A fungal infection that is associated with asthma, atopy (genetic tendency to develop allergy) and cystic fibrosis; may cause bronchiectasis and eosinophilia Presents with worsening asthma & lung function Diagnostic features include a high total IgE, specific IgE to Aspergillus and positive serum IgG to Aspergillus. CT imaging of the thorax may demonstrate central bronchiectasis. Treatment of ABPA is with corticosteroids and antifungal therapy

Allergic bronchopulmonary aspergillosis (ABPA)

o Allergic Bronchopulmonary aspergillosis o Wheezing, breathlessness, loss of lung function, bronchiectasis o Airways inflammation o IgE and G reaction to Aspergillus o Responds to steroids and/or antifungal therapy

Allergic forms of aspergillosis--asthma and CF

stem cells are acquired from a donor who has been determined to be human leukocyte antigen (HLA)-matched to the recipient • Transplantation that occurs in people that are not related • APC migration e.g. kidney transplant: kidney is full of antigen presenting cells: new kidney goes in that is foreign and APCs go to lymph nodes where they are recognised • Transplant = very foreign as polymorphisms so very aggressive and intense immunological response • Autologous vs allogeneic cell: self cells not recognised therefore no immune response = autologous • Allogeneic = very different therefore immune response and why in transplant = best match as possible and immunosuppression

Allogeneic transplantation

• Alpha 1 antitrypsin is a protein made in the liver excreted into blood where it functions to neutralise proteolytic enzymes, particularly from active polymorphs. • This inborn error of metabolism results in abnormal structure of A1AT, which folds wrongly and can't be excreted from hepatocytes. There are many types, the commonest is PiZZ • The accumulated A1AT forms globules of glycoprotein that stain positive with PAS diastase stain. • This damages liver cells, and may lead to fibrosis and cirrhosis - very variable, sometimes in childhood, sometimes in adulthood. • The low levels of A1AT in the serum make the patient susceptible to emphysema of the lung, especially if the patient also smokes. • Abnormal anti-protease which cannot be exported from hepatocyte o See PAS+ve globules in hepatocytes • Accumulates in liver cells and injures them - cirrhosis • Insufficient in blood, failure to inactivate neutrophil enzymes o emphysema

Alpha 1 antitrypsin deficiency

• Aminotransferases o Alanine/ ALT o Aspartate/ AST o Found in the cell and only released by cellular damage • ALT is more specific for liver than AST AST also found in muscle and RBCs • Tumour markers: alpha fetoprotein: primary hepatocellular carcinoma

Aminotransferases used to measure hepatocyte damage

Obtaining a blood specimen

An accurate FBC (full blood count) & correct interpretation of a blood film appropriate sample from the patient collected into EDTA anticoagulated blood mixed well [K2EDTA] = 1.5 - 2.2 mg ml-1 blood should be filled to the line on tube Samples should get to the lab promptly since EDTA artefact can affect the results.

Monocytes

An agranular leukocyte that is able to migrate into tissues and transform into a macrophage. Phagocytic & antigen-presenting cells Migrate to tissues & are then identified as "macrophages" or "histiocytes" e.g. Kupffer cells in liver e.g. Langerhans cells in skin

Patients with similar presenting symptoms e.g. chest pain Same age Same gender Hospitalised normal Same underlying disease

An appropriate normal population

Bacteria that do not require oxygen to live

Anaerobic bacteria

Any of the following criteria must be filled: 1. Sudden onset of an illness (minutes to several hours), with involvement of the skin, mucosal tissue, or both (e.g. generalised hives, itching or flushing, swollen lips/tongue/uvula). • AND one of the following: o Sudden respiratory symptoms and signs. o Sudden reduced BP or symptoms of end-organ dysfunction. 2. Two or more of the following that occur suddenly after exposure to a likely allergen or other trigger for that patient (minutes to several hours): • Sudden skin or mucosal symptoms and signs. • Sudden respiratory symptoms and signs. • Sudden reduced BP or symptoms of end-organ dysfunction. • Sudden GI symptoms. 3. Reduced blood pressure after exposure to a known allergen for that patient (minutes to several hours): • Infants and children: o Low systolic BP or greater than 30% decrease in SBP. • Adults: o Systolic BP of less than 90mmHg or greater than 30% decrease from that person's baseline.

Anaphylaxis

• Very rare cancer • Aggressive tumour of blood vessels: malignant • Strongly associated with toxins o Vinyl chloride (use to make records, exposure = inc risk) o Thorotrast (contrast agent), predispose people to this cancer as used to use • No treatment, palliative care

Angiosarcoma

• Acute or chronic inflammation of the skin and contiguous labial mucosa located at the lateral commissures (i.e. corners of the mouth) of the mouth • Usually involves the lip vermillion and the vermillion border, but the surrounding skin and oral mucosa may also be affected • Typical presents with erythema, maceration (softening and breaking down of skin due to prolonged exposure to moisture), scaling and fissuring at the corners of the mouth • Lesions are most often bilateral and may be painful • Caused by excessive moisture and maceration from saliva and secondary infection with C albicans or less commonly S aureus • Can occur at any age without sex predilection, especially common in older inds wearing dentures

Angular Cheilitis

One antimicrobial diminishes the activity of another

Antagonism

o Genus of moulds—filamentous fungi o Produce aireborne spores o Exposure to Aspergillus spores is universal by inhalation o Airways may be colonised by Aspergillus sp o Examples of medically important species: Aspergillus fumigatus Aspergillus Niger Aspergillus flavus Aspergillus terreus

Aspergillus

rheumatoid arthritis

Anti-CCP is a specific test for?

o 3 different agents available (anakinra, rilonacept and canakinumab) o Used in treatment of AOSD and autoinflammatory syndromes

Anti-IL-1

o Blocks IL-6 receptor o Used in therapy of RA and Adult Onset Still's Disease o May cause problems with control of serum lipids

Anti-IL-6 (Tocilizumab)

o First biologics to be successfully used in therapy of RA (5 different agents now licensed) o Used in a number of other inflammatory conditions (Crohn's, psoriasis, ankylosing spondylitis) o Caution: increase risk of TB

Anti-TNF

Primary biliary cirrhosis

Anti-mitochondrial Antibody is a specific test for?

β-lactams-->penicillins, cephalosporins, carbanepem Glycopeptides

Antibacterial agents which inhibit cell wall synthesis

there is lots of variation between how the antibiotic is distributed in the body and how it is cleared from the body

Antibiotic Pharmacokinetics

o Short course for all o Long course for all o Biomarker driven o Imaging strategy • Choice depends on: o Evidence o Clinical factors o Social factors o Costs o Resources available

Antibiotic duration strategies What does the choice depend on?

term used to describe the time since the widespread availability of antibiotics to treat infection

Antibiotic era

There are red flag features of sepsis on admission Consider giving them if they have severe acute sepsis Immunocompromised

Antibiotics are not recommended for gastroenteritis unless

Quinolones e.g. ciprofloxacin-->Anthropathy: inflammation of joints (arthritis) Trimethoprim (folate antagonisst)-->teratogenic in first trimesteri.e. can cause birth defects Aminoglycosides-->otoxic (toxic to ear) Nitrofurantoin-->neonatal haemolysis

Antibiotics not to have when pregnant and what their risks are

B-lactams: penicllins, cephalosporins, carbapanems can be used where benefits outweigh the risk

Antibiotics safe in pregnancy

o Quinolones (ciprofloxacin) - damage to cartilage o Trimethoprim - folic acid antagonist o Tetracyclins - deposits and stains bones/teeth

Antibiotics to avoid in pregnancy

nitrofurantoin trimethoprim pivemacillinam

Antibiotics used to treat lower UTI

IV cefuroxime IV getamicin oral/IV ciprofloxacin oral/IV co-amoxiclav

Antibiotics used to treat upper UTI

Pneumonia resulting from the abnormal entry of fluids e.g. food, drinks, stomach contents, etc. into the lower respiratory tract Patient usually has impaired swallow mechanism Anaerobes may be implicated

Aspiration pneumonia

o Confirms exposure to a specific microorganism - Cultivable and non-cultivable organisms - Restricted to patients with a detectable antibody response • Often too late to inform antimicrobial therapy decisions

Antibody testing--uses and limitations

Echinocandins

Antifungal agents which inhibit cell wall syntheiss

Mi-2

Autoantibody in dermatomyositis

chemicals that prevent cell division by inhibiting formation of substances necessary to make DNA; used in cancer chemotherapy • Inhibit nucleotide (purine) synthesis • Azathioprine o Guanine anti-metabolite o Rapidly converted into 6-mercaptopurine • Mycophenolate Mofetil o Non-competitive inhibitor of IMPDH (Inosine-5′-monophosphate dehydrogenase) o Prevents production of guanosine triphosphate • T and B cells effects o Impaired DNA production o Prevents early stages of activated cells proliferation

Antimetabolites

Topical agents for mild to moderate Topical plus a systemic antibiotic like flucloxacillin for severe acute otitis externa

Antimicrobial management of otitis externa

Management of intra-amniotic infections

Antimicrobials and delivery of the foetus Antimicrobials should be administered at the time of diagnosis (not after delivery)

• Antibodies produced by the patient in the patient's blood that bind to the cell nucleus. • Uses indirect immunofluorescence. • We can then be more specific and identify subtypes of antibody that bind to different bits of the nucleus.

Antinuclear antibodies

Receiving immunosuppressive therapy Primary immunodeficiency Post transplant

Antivirals should be given to patients who are immunocompromised, why may a patient be immunocompromised?

Centromere

Autoantibody in limited systemic sclerosis

inflammation of the appendix • Complicated appendicitis: Surgical management plus Abs • Uncomplicated appendicitis: surgical management plus single dose antibiotic prophylaxis o Difficult to diagnose, CT misses 10% of complicated appendicitis o Expectant management: 20% of all appendixes removed are normal o Antibiotic management - Supported by some academics but not accepted by surgical community - 25-30% of patients undergo appendicectomy in the next year - Potentially antibiotics of no efficacy if the pathology is similar to diverticulitis

Appendicitis

a fungal ball generally found in a preformed cavity of the lung, composed of a mass of Aspergillus hyphae o Patients get these who have cavities from previous TB, sarcoid, surgery o Aspergillomas form solid balls of fungus o IMPORTANT: aspergillomas are often immobile (indolent) but may break up causing haemoptysis and are potentially fatal

Aspergilloma

Jo-1

Autoantibody in polymyositis

broad--so are last line antibiotics

Are carbapenems broad or narrow spectrum?

narrow

Are penicillins broad or narrow spectrum?

• Most cases of ischaemic colitis affect left colon • Right colon: 35% (caecum/ascending colon only in 19%) • Transverse colon: 10% • Left colon (rectum to splenic flexure): 33% • Distal colon (rectum and sigmoid colon): 25% (rectum involved in 2.3% of all cases) • Pan-colonic: 7% o Pancolic: the whole large intestine • Water shelf area around the splenic flexure, less blood supply therefore greater risk

Areas in the colon vulnerable to ischaemic colitis

Aspergillosis is an infection caused by Aspergillus, a common mold (a type of fungus) that lives indoors and outdoors. Most people breathe in Aspergillus spores every day without getting sick. Immunocompromised patients & those with lung disease are at a higher risk of developing health problems due to Aspergillus. The types of health problems caused by Aspergillus include allergic reactions, lung infections, and infections in other organs

Aspergillosis

Causes of malignant mesothelioma

Asbestos - the big one, 80 to 90% of cases Strong association with asbestos dust exposure above the general population exposure level but the exposure can be quite low level The link was first identified in South African asbestos mining towns in the 1960 Mesothelioma develops 15 years to over 60 years after exposure The risk increases with cumulative exposure level and time from exposure Is the background level safe? - Not certain but fairly safe Estimated 1 to 2 "spontaneous" cases per million persons per year Thoracic irradiation BAP1 (BRCA1-associated protein 1) mutations Germline mutations in a familial cancer syndrome with uveal melanomas and mesotheliomas

Effect of asbestos on the skin

Asbestos corns - benign hyperkeratotic wart-like skin lesions Asbestos caused about 5000 UK deaths in 2014

Effect of asbetsos on the lung itself

Asbestosis - 431 UK deaths in 2014 Lung carcinoma - about 2000 UK deaths in 2014

• History: • Indication for the drug. • Detailed description of the reaction. • Time between drug intake and onset of symptoms. • Number of doses taken before onset. • Management: • Intradermal testing - skin test isn't sensitive enough. • Dermal challenge. • Desensitisation

Aspects to consider in drug allergy

CURB 65 score Confusion Urea Respiratory rate Blood pressure

Assessment of disease severity in pneumonia

Low risk HPV types

Associated with genital warts and other low-grade cytological abnormalities: 6, 11, (40, 42, 43, 44, 53, 54, 61, 72, 73 and 81) Lower genital tract warts (condylomata = benign squamous neoplasms), low grade 'IN's Very rare in malignant lesions

Diffuse pleural fibrosis

Associated with high level asbestos dust exposure Usually bilateral Dense cellular collagen not extending into interlobar fissures Prevents normal expansion and compression of the lung during breathing causing breathlessness It is a UK Government Prescribed Occupational Disease for specified high exposure occupations that is eligible for Industrial Injuries Disablement Benefit

High risk HPV types

Associated with high-grade pre-invasive and invasive disease are 16, 18, (31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68) 99.7% of cervical cancers contain HPV DNA Types 16, 18 associated with ~70% of cervical cancers

Parietal pleura fibrous plaques

Associated with low level asbestos dust exposure Asymptomatic May be visible on chest radiographs Dense poorly cellular collagen It is not a UK Government Prescribed Occupational Disease therefore it is not eligible for Industrial Injuries Disablement Benefit

A chronic allergic disorder characterized by episodes of severe breathing difficulty, coughing, and wheezing. • Widespread, reversible narrowing of the bronchial tree that changes in severity over shorts periods of time, either spontaneously or under treatment • Smooth muscle constricts and narrows the bronchioles • Twitchy airways

Asthma

• Production of metabolites • Clearance of endogenous substances: bilirubin etc. • Clearance of exogenous substances: drugs and toxins • Imaging, biopsy

Available liver function tests i.e. what do they test for?

Excess inflammation; dry skin, redness, and itching from allergies and irritants. • Contact - allergic/non-allergic. • Clinically - intense itching, blistering/weeping, cracking of skin. • House dust mite now thought to be major trigger in atopic disease. • Topical steroids and moisturisers.

Atopic dermatitis

atopic dermatitis, allergic rhinitis, asthma

Atopic triad

Cervical screening programme

Available test has high sensitivity and specificity Test is not harmful Defined pre-invasive stage Long enough to allow intervention Simple, successful treatment Is not a test for cancer Regular attendance prevents around 90% of cancer Rate of cancer would be 50% higher without screening

• Consider in Immunosuppressed: o Haemato-Oncology- on chemotherapy, solid organ transplant o Steroids, Diabetes, CKD, Underlying disease (HIV, Congenital, liver etc.) o Travel • Viral (eg. RSV, CMV)- viral PCR • Fungal (eg. Aspergillus)- Culture, Aspergillus Antigen • Pneumocystis- PCP PCR • Not looked for routinely, need to guide lab with history • Usually best investigates by deep resp samples (BAL)

Atypical infections

Atypical organisms have an atypical/no cell wall and therefore do not respond to penicillin These are in a separate group as the clinical presentation and treatment are slightly different Atypical organisms that cause pneumonia: Mycoplasma pneumoniae Legionella pneumophilia Chlamydophila pneumoniae Chlamydophila psittaci Coxiella burnetii

Atypical organisms that cause community acquired pneumonia

La

Auto-antibody in Sjogren's syndrome

Ro

Auto-antibody in neonatal lupus erythematosus

o Insulin autoantibodies o Glutamic acid decarboxylase autoantibodies (GAD) o Islet antigen-2 autoantibodies (IA-2) o ZnT8 transporter autoantibodies

Autoantibodies in type 1 diabetes

• Non-pathogenic. • Several types: • Islet cell antibodies. • Anti-GAD65 and anti-GAD67. • Anti-insulinoma antigen 2 (IA-2). • Insulin autoantibodies (IAAs). • Disappear with progression of disease and total destruction of B islet cells.

Autoantibodies in type 1 diabetes mellitus

dsDNA

Autoantibody in SLE

• Distinct clinical entities. • Breakdown of self-tolerance. • Environmental factors acting on favourable genetic background. • Wide variety of pathogenic mechanisms between diseases. • Causes of autoimmune disease: • Genes - from birth but most autoimmune diseases don't present until middle age, so there's a lag in presentation. Which makes you think there's an influence from the environment. • Immune regulation. • Environment - specific factors for specific diseases.

Autoimmune disease

• ANA ANCA. • CK. • RF. • Anti-CCP antibody. • Complement.

Autoimmune disease tests

• Autoimmune liver diseases are chronic liver diseases due to disturbance of the immune system with recognition of 'self antigens' leading to chronic inflammation and destruction of hepatocytes (autoimmune hepatitis) or bile ducts (chronic biliary diseases). • Autoimmune hepatitis is commoner in women, and can present as acute or chronic hepatitis • Diagnosis is based on autoantibodies, raised IgG and raised ALT • Liver biopsy is important for diagnosis, and characteristically shows prominent interface hepatitis with lots of plasma cells • Treatment is with immunosuppression with the aim of preventing progression of fibrosis to cirrhosis. • Some patients have an overlap of autoimmune hepatitis and an autoimmune biliary disease. • Auto-antibodies (anti-nuclear, smooth muscle, etc.), raised IgG, ALT, other autoimmune diseases, • Liver biopsy - plasma cells, interface hepatitis

Autoimmune hepatitis

Autoimmune hepatitis is a disease in which the body's own immune system attacks the liver and causes it to become inflamed. • Anti-mitochondrial Ab specific for primary biliary sclerosis. • Anti-smooth muscle and anti-liver/kidney/microsomal (LKS) Abs are found in autoimmune hepatitis. • Antibodies detected by IF screening using rodent tissue block (oesophagus, liver and kidney) and antigen specific ELISA.

Autoimmune liver disease

• The adaptive immune system recognises and targets the body's own molecules, cells and tissues (instead of infectious agents and malignant cells). • Main characteristics: • T cells that recognise self-antigens. • B cells and plasma cells that make autoantibodies. • Inflammatory in target cells, tissues and organs is secondary to actions of T cells, B cells and autoantibodies.

Autoimmunity

• Main characteristics: • Seemingly spontaneous attacks of systemic inflammation. • No demonstrable source of infection as precipitating cause. • Absence of high-titre autoantibodies and antigen-specific auto-reactive T cells. • No evidence of auto-antigenic exposure. • E.g. Periodic fever syndromes (FMF, TRAPS, CAPS and HIDS).

Autoinflammation

Onset is 2-6 hours after ingestion Causes vomiting, no fever, little or no diarrhoea Associated with cooked rice and other starchy foods

Bacillus cereus enterotoxin that has a heat stable emetic form

there are 2 enterotoxins , one is a heat stable emetic (causes vomiting) form the other enterotoxin is the heat labile diarrhoeal form

Bacillus cereus enterotoxins

• Sexually transmitted • Incubation 5-28 days • Symptoms/signs: Men=asymptomatic • Women=smelly vaginal discharge, dyspareunia (pain during sex), dysuria (difficulty passing urine) and lower abdominal discomfort, punctuate haemorrhages on cervix (strawberry cervix—haemorrhages on cervix)

Background and symptoms of trichomoniasis

• Human is an accidental host • The human who is usually the definitive host is the intermediate host in this life cycle • Usual hosts are sheep and dogs that eat contaminated raw meat • Found all over the world wherever sheep are farmed

Background of Hydatid disease

• More than 1 billion people affected worldwide (approximately 1/7 world population) • Peak prevalence in 3-8 year olds • Areas of poor hygiene • 1 adult worm can produce 200,000 eggs per day • Acquired by ingestion of eggs

Background of ascariasis

• Causes diarrhoeal disease • Human to human spread with animal reservoir (cattle, sheep, goats) • Faecal-oral spread • World-wide distribution (especially temperate and tropical countries) • Sporadic cases can lead to outbreaks

Background of cryptosporidosis

Faecal oral transmission Spectrum of disease: asymptomatic carriage to severe diarrhoea and malabsorption Can cause chronic disease

Background of giardisis

• 300-500 million people infected every year • 1-3 million deaths per year, mainly in young children • ~2000 cases/year in UK - 70% P. falciparum • (Travel clinic)

Background of malaria

Snail is the intermediate host Causes chronic disease resulting in bladder cancer and liver cirrhosis

Background of schistosomiasis

Typical and atypical

Bacteria that cause community acquired pneumonia are divided into two categories

Campylobacter Salmonella Shigella E Coli Yersinia Vibrio Cholerae C diff

Bacteria that cause gastroenteritis

o Neisseria meningitidis o Streptococcus pneumoniae o Listeria monocytogenes o Streptococcus agalactiae o Haemophilus influenzae o Staphylococcus aureus

Bacteria that cause meningitis

o Chlamydia species o C. trachomatis - commonest cause of STI o Mycoplasma species o M. pneumoniae - common cause of respiratory tract infections

Bacteria without a conventional cell wall

• Affects particular patients: abnormality in blood flow of bowels which allows for stasis • Overgrowth of bacteria on the small bowel is believed to be associated with malabsorption or chronic diarrhoea. • Overgrowth of bacteria may result from achlorhydria (e.g. after gastric surgery), impaired motility, blind loops of bowel, surgery and radiation damage. • Bacteria may bind vitamins e.g. B12, use nutrients, produce metabolites e.g. fatty acids • Treatment: dietary changes, surgical, motility, non-absorbable antibiotics.

Bacterial overgrowth

Very Finely Proficient At Cell Murder: Vancomycin Fluoroquinolones Penicillin Aminoglycosides Cephalosporins Metronidazole

Bactericidal antibiotics

Kill bacteria/fungi e..g by acting on the cell wall

Bacteriocidal/fungicidal

erythromycin, clindamycin, sulfamethoxazole, trimethoprim, tetracycline, chloramphenicol

Bacteriostatic antibiotics

Inhibit growth of bacteria or fungi e.g protein synthesis inhibitors, these prevent them from multiplying and spreading infection

Bacteriostatic/fungistatic

Early treatment with mortality and morbidity benefit If clinically stable, narrow spectrum antibiotics may be administered and the response can be assessed If clinically stable, an oral antibiotic may be administered and the response assessed Prevent infection metastases

Benefits of early antibiotic therapy

Leiomyoma (uterine fibroids) Risk factors History Investigations Treatment Prognosis

Benign myometrial tumours with E2/P4 depndent growth Around 20% women 30-50s Risk factors-gentics, nulliparity (no kids), obesity, PCOS, Hypertension (HTN) Hx-often asymptomatic, menomettorrhagia (bleeding between periods which can cause iron deficienct anaemia), subfertility, pregnancy problems, pressure sores Ix-bimanual examination, ultrasound Treatment-Medical e.g. NSAIDs Fe2+ Non-medical e.g. artery embolization Prognosis-menopausal regression, malignancy risk 0.01%

o Adenoma: most common, arises from the epithelium, lining of the large bowel o Lipoma o Leiomyoma o Haemangioma o Neurofibroma o Ganglioneuroma

Benign neoplastic polyps

Vancomycin and gentamicin

Best empirical treatment for catheter associated blood stream infection?

Products of active osteoblasts: Alkaline phosphatase (TAP, BAP) Osteocalcin Procollagen type 1 propeptides P1NP Bone resorption-->degradation products of bone collagen: Hydroxyproline Pyridinium crosslinks Crosslinked telopeptides of type 1 collagen (NTX, CTX) Osteoclast enzymes: Tartrate-resistant acid phosphatase (TRACP 5b) Cathepsin K

Biochemical markers of bone turnover

Faecal-oral spread

How are hepatitis A and E spread?

Describe red blood cells (erythrocytes)

Bi-concave discs, 7.5 µM diameter Lifespan 120 days in blood Contain Haemoglobin 333,200 x 10^6 red cells

• Chronic biliary diseases both result in gradual destruction of the intrahepatic bile ducts = chronic cholestasis, itching, fatigue, then cirrhosis • Can be treated with urso-deoxycholic acid = bile salt analogue which delays disease progression

Biliary diseases

• Impaired excretory function: inc conjugated bilirubin • Inc synthesis of enzymes by cells lining the bile canaliculi: ALP and yGT • Alkaline Phosphatase (ALP) o Elevated due to inc production by cells lining the bile canaliculi and overflow into blood o Due to: - Cholestasis: intra or extrahepatic - Infiltrative diseases - Space occupying lesions: tumours - Cirrhosis o Multiple sites of production: liver, bone, intestine, placenta • ALP isoenzymes o Liver and bone ALP isoenzymes separated by electrophoresis • Gamma glutamultransferase (yGT) o Can support a liver source of raised ALP o Elevated due to structural damage o Can be induced by: - Alcohol - Enzyme inducing agents e.g. anti-epileptics - Fatty liver e.g. due to alcohol, diabetes or obesity - Heart failure - Prostatic disease - Pancreatic disease: acute and chronic pancreatitis, cancer - Kidney damage: ARF< nephrotic syndrome, rejection

Biliary tract damage

Cholangitis Cholecystitis

Biliary tract infections examples

Blocks viral binding sites (neutralization) Agglutination of microbes Precipitation of dissolved antigens Activation of complement system

Binding of antibodies to antigens inactivates pathogens by:

Blood borne

How are hepatitis B and C spread?

• antibodies or other peptides • inhibit inflammatory cytokine signals e.g.tumour necrosis factor or TNF, inhibiting T-cell activation, or depleting B-cells. • E.g. used in severe rheumatoid arthritis • Risk of tuberculosis, herpes zoster, Legionella pneumophila, and Listeria monocytogenes

Biologics

Substances that produce biologic responses within the body; they are synthesized by cells of the human body, animal cells, or microorganisms. • Anti-cytokines (TNF, IL-6 and IL-1) • Anti-B cell therapies • Anti-T cell activation • Anti-adhesion molecules • Complement inhibitors • Check point inhibitors

Biologics examples

haematology

Biology and pathology of the cells that normally circulate in the blood

Hepatitis viruses: Hep B and Hep C Retroviruses: HIV 1,2 HTLV 1,2 (human t cell leukaemia type 1 and 2)

Blood borne viruses

Urea and electrolytes Parathyroid hormone (this would expected to be low because blood calcium is controlled by parathyroid hormone)

Blood test you would do in someone with a high calcium level

• AST/ ALT elevated and normal ALP: approx. 90% have hepatitis • AST or ALT normal and elevated ALP: approx. 90% have obstructive jaundice

Blood tests with jaundice

Metastatic disease Hyperparathyroidism Osteomalacia/rickets Osteoporosis Paget's disease

Bone disorders

Future of treatment for breast cancer

Breast cancer molecular subtypes : Evolution in understanding and treatment of disease. Hormonally targeted therapies Tamoxifen, Aromatase Inhibitors Bisphosphonates Her-2 targeted approach Trastuzumab etc.

Treatment of puerperal endometritis

Broad-spectrum intravenous antimicrobials - continued until the patient has been apyrexial for 48 h

- Permanent dilation of bronchi and bronchioles caused by destruction of the muscle and elastic tissue - Results from chronic necrotizing infection - Rare ( for now.....) Caused by infections

Bronchiectasis

Characteristic patchy distribution centred on inflamed bronchioles and bronchi then subsequent spread to surrounding alveoli

Bronchopneumonia

Endometrial adenocarcinoma

By far the most common cancer of the uterus, this type develops from the cells that line the uterus of the female genital tract 9200 new cases,/2500 deaths Hx-pre-menopausal bleeding, intermenstrual bleeding, pain if late periods Ix-ultrasound, biopsy, hysteroscopy Staging: FIGO Treatment: medical, surgery, adjuvant therapy Prognosis: Stage 1=90% 5 year survival, stage 2-3=<50%

T helper cells

CD4 cells

• Failure to maintain hydration of macromolecules in the lumen of the ducts of the lungs, pancreas, intestine, liver and vas deferens-->causes secretions to precipitate and cause obstruction • Digestive enzyme deficiencies: malnutrition • Lung disease: increased bacterial colonisation, neutrophils accumulate, elastase is secreted which digests lung proteins causing tissue damage, dead neutrophils release DNA which increases the viscosity of CF sputum o Infection and persistent inflammatory state

CFTR dysfunction

sample contaminated with EDTA

Low calcium, low magnesium, high potassium

• CFTR facilitates production of thin, watery, free-flowing mucus • Lubricating airways and secretory ducts • Protecting the lining of the: o Airway o Digestive system o Reproductive system • So that macromolecules e.g. digestive enzymes can be secreted smoothly out of secretory ducts

CFTR protein function

• antigen specific • Slower response, but more potent • Subsequent exposure- more effective response • memory

Describe adaptive immunity

Point scoring system used for evaluating the risk of mortality with pneumonia CONFUSION UREA RESPIRATORY RATE BLOOD PRESSURE

CURB-65

• Hypertension • Hirsutism • Nephrotoxicity • Hepatotoxicity • Lymphomas • Opportunistic infections • Neurotoxicity • Multiple drug interactions (induce P450)

Calcineurin/mTOR-side-effects

• Total body calcium: 1kg o bone: 99% o intracellular: 1% o extracellular 0.1% - total plasma calcium: 2.2-2.6 mmol/L - calcium <1.6 or >3.5 mmol/L = medial emergency requiring immediate treatment • ionised free Ca2+ (50%): biologically active o bound to plasma membranes: 41%: predominantly bound to albumin • complexed to anions 9% e.g. phosphate, citrate, bicarbonate - total Ca = ionised Ca + bound Ca + Complexed Ca

Calcium distribution in the body

• Gram negative C jejuni (85%), C coli (15%) • GNB • Curved or spiral, 'seagull' • Highly motile, with flagellum at 1 or both poles • Culture: charcoal or blood • Colonies like spreading fluid droplets, colorless-grey • Oxidase positive • Incubation period:1-10d • Mild-severe diarrhoea • Fever, abdo pains • Source: poultry, eggs, meat • Sporadic infections >> outbreaks • Complication: Gullain-Barre syndrome

Campylobacter

Primary pleural neoplasms

Can be: Benign/low grade malignant--uncommon/rare Includes low grade mesothelial tumours Malignant--malignant mesothelioma is common Others malignant neoplasms are uncommon/rare

Being pregnant (women are more commonly sensitised than males) Previous transplants Lots of transfusions: lots of WBCs given in blood transfusions back in the past, however cleared before they are given now but there can still be a bit of leukocytes as hard to clear completely

Can make people sensitised in 3 ways

o Large genus of yeasts o Often colonises the mucosal surfaces and GI tract in healthy people o Cause of superficial mucosal (oral and vaginal) disease "thrush", also occasionally skin disease and keratitis o Cause of systemic disease, once present in circulatory system, can infect almost any organ in the body o Caused by range of Candida species - Candida albicans - Candida glabrata - Candida parapsilosis - Candida krusei

Candida

o Mainly in HIV o Candida oesophagitis in 10-20% patients with oropharyngeal disease o Pain/difficulty on eating/swallowing (dysphagia) o Diagnosed by endoscopy with biopsy

Candida oesophagitis

o Complication of peritoneal dialysis o During surgery there may be a perforation of the bowel-->mixed bacterial/yeast infection o Consequences: - Fever - Abdominal pain - Nausea - Vomiting o Diagnosis occurs by a culture of Candida from the peritoneal fluid o Treatment by source control/drainage and antifungals

Candida peritonitis

Canidida in the blood culture - Remove lines (where possible) - Start antifungal therapy - Check heart and eyes

Candidaemia (type of ssytemic candidosis) Define it and how you would respond to a patient with candidaemia

A rare consequence of candidaemia Occurs in IV drug abusers and those who have had valve surgery Vegetations are seen on the heart valves Results in: -Fever -Weight loss -Fatigue -Heart murmur Difficult to treat without a valve replacement

Canidida endocarditis

Directly cytotoxic Activation of complement Interfere with normal physiological functions

Describe autoreactive B cells and autoantibodies

Intraepithelial neoplasia

Carcinoma in situ whose component cells do not violate the basement membrane Cervical intraepithelial neoplasia-CIN Cervical glandular intraepithelial neoplasia-CGIN Vulval intraepithelial neoplasia - VIN Vaginal intraepithelial neoplasia - VaIN Anal intraepithelial neoplasia - AIN = dysplasia

o Association with H. pylori o Association with diet: salt, low fruit and veg o No association with GO reflux o Decreased incidence in recent yrs

Carcinoma of gastric body/antrum

- Potential for carotid artery erosion - Carotid sheath abuts all 3 layers of the deep cervical fascia - Infection may arise by spread from parapharyngeal space, submandibular space (Ludwig's angina)/ suppuration of the deep cervical lymph nodes - No characteristic symptoms or signs - History of sore throat is usually but not always present: can be mild/ unilateral - Latent period of up to 3wks before obvious manifestations of a deep neck space infection - Patient = toxic condition/ fever of undetermined origin - Trismus is absent - Signs of local suppuration may be subtle because of tight connective tissue around and within carotid sheath - Some patients diffuse swelling along the sternocleidomastoid muscle with marked tenderness and torticollis (abnormal head/neck position) to the opposite side - Carotid artery mycotic aneurysms: mortality rate 20% - Erosion of carotid artery comes from an anrteritis due to contiguous inflammation = formation of false aneurysm = rupture - Erosion and rupture = recurrent small haemorrhages from the nose, mouth or ear (herald bleeds) - Followed by haematoma formation in the surrounding tissues, a protracted clinical course = onset of shock to exsanguination - Ligation of artery may be necessary in cases of major haemorrhage - Mortality rate = high

Carotid sheath involvement in parapharyngeal space infections

o Longstanding gastro-oesophageal reflux (or the squamo-columnar junction)

Cause of Barerrett's oesophagus

kills them

what does HIV do to CD4 cells

Defect/absence of critical T cell molecule TCR, common gamma chain Loss of communication MHCII deficiency Metabolic Adenosine deaminase deficiency

Causes of SCID

Infection could be caused by bacteria, mycobacteria, fungi or parasites infections of the mastoid, middle ear, nasal cavity, nasal sinuses, abscessed teeth, skull fractures and prior brain trauma or surgery, blood post-op

Causes of a brain abscess

o Damage hepatocytes, short term: o Inflammatory injury: hepatitis: - Viral - Drugs - Autoimmune - Unknown: seronegative - All have similar pathology spectrum o Toxic/ metabolic injury: alcohol, drugs (paracetamol) • Acute hepatitis = due to liver cell injury, independent of its cause • Commonest causes of severe liver cell injury in the UK = alcohol and paracetamol toxicity • Causes of severe inflammatory injury (acute hepatitis on biopsy) are viral (Hep A, B, E), drug induced liver injury (DILI) and autoimmune hepatitis • Histology for them = similar, in many cases with severe acute hepatitis on histology no cause can be identified = seronegative hepatitis • Acute hepatitis: the injury and death of ind hepatocytes results in a disordered appearance of the liver cell plates = lobular disarray

Causes of acute hepatitis

• Acute hepatic failure = rare o Severe rapid liver injury • Chronic hepatic failure: end stage chronic liver disease o Ascites o Muscle wasting o Bruising o Gynaecomastia-->enlarged breasts o Spider naevi o Caput medusa = variceal umbilical vein collaterals

Causes of acute vs chronic hepatic failure

• Drooling, thumb sucking, and lip licking are frequent causes of angular cheilitis in young children • Less common causes in both adults and children: o nutritional deficiencies o type 2 diabetes o immunodeficiency o irritant or allergic reactions to oral hygiene products or denture materials o medications causing dryness o xerostomia: dry mouth syndrome caused by a change in saliva composition

Causes of angular cheilitis

Primarily environmental Poor diet: red meat, high fat, low fibre Obesity or inactivity Alcohol, smoking and radiation Lesser importance Inherited factors: defined syndrome or non-specific association (link in family but no obvious hereditary syndrome) Lynch Syndrome or FAP Inflammatory bowel disease Particularly patients with long term ulcerative colitis

Causes of bowel cancer

Something that doesn't go away Persistence of abnormal liver tests for more than 6 months Continuing liver damage is combined with the body's attempts at regeneration of hepatocytes and repair: this would be healing through angiogenesis and fibrosis Balance of damage and attempts at repair Causes: o immunological injury: virus, autoimmune, drugs o toxic/ metabolic injury: fatty liver disease, alcohol, non-alcoholic fatty liver disease (NAFLD), drugs - most common cause o genetic inborn errors: iron, copper, alpha 1 antitrypsin o biliary disease: autoimmune, duct obstruction, drugs o vascular disease: clotting disorders, drugs • liver biopsy can usually identify which of these 5 groups is the cause of chronic liver injury in an individual patient

Causes of chronic hepatitis

• Cirrhosis = end point of chronic liver disease • Cirrhosis develops over months to decades: rate of progression = variable • Cause of cirrhosis: cause does not go away: o Alcohol o Non-alcoholic steatohepatitis: metabolic syndrome o Chronic viral hepatitis: B, C o Autoimmune liver disease: autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis o Metabolic: iron, copper, alpha 1 antitrypsin • The liver is converted into a mass of regenerating nodules wrapped by fibrous scar tissue • Microscopically: regenerative nodules of hepatocytes, surrounded by sheets of fibrous tissue • Progression of fibrosis in chronic liver disease: encircles nodules of regenerating hepatocytes

Causes of cirrhosis

o Elevated due to inc production by cells lining the bile canaliculi and overflow into blood o Due to: - Cholestasis: intra or extrahepatic - Infiltrative diseases - Space occupying lesions: tumours - Cirrhosis o Multiple sites of production: liver, bone, intestine, placenta

Causes of elevated ALP

urethritis (gonorrhea)

what does Neisseria gonorrhoea cause?

- Alcohol - Enzyme inducing agents e.g. anti-epileptics - Fatty liver e.g. due to alcohol, diabetes or obesity - Heart failure - Prostatic disease - Pancreatic disease: acute and chronic pancreatitis, cancer - Kidney damage: ARF< nephrotic syndrome, rejection

Causes of elevated gamma glutamyltransferase (yGT)

PTH mediated o Malignancy e.g. tumours secreting osteoclast-activating cytokines (with or without bone metastases) o Tumours secreting PTHrp o Cells with 1α hydroxylase activity (activation of vitamin D) e.g. lymphoma o Vitamin D intoxication (excess vitamin D) o Chronic granulomatous disorders e.g. sarcoidosis Medications - Thiazide diuretics, Lithium, Teriparatide, Theophylline toxicity o Immobilisation o Other endocrine conditions - Hyperthyroidism, acromegaly, phaeochromocytoma, adrenal insufficiency -Bone disease • PTH mediated o Sporadic primary hyperparathyroidism o Familial - MEN1 and 2A - Familial hypocalciuric hypercalcaemia - Familial isolated hyperparathyroidism

Causes of hypercalcaemia

Renal failure like AKI or CKD Hypothyroidism Vitamin D toxicity Spurious-->haemolysis, delayed separation of sample, assay interference

Causes of hyperphosphataemia

• Vitamin D deficiency o Dietary / malabsorption o Hepatic disease o Renal disease o End organ vitamin D resistance (there is enough vitamin D but there is something wrong with vitamin D receptors, so there is no response) • Inadequate dietary calcium intake • Hypoproteinaemia • Hypoparathyroidism o Primary o Secondary to magnesium deficiency o Pseudo-hypoparathyroidism (end-organ resistance to PTH) • Pseudo-hypoparathyroidism: (End organ PTH resistance) • High phosphate: (will complex with calcium) • High citrate: (E.g. from citrated blood products, will complex with calcium) • Spurious causes: EDTA contamination of sample

Causes of hypocalcaemia

• Poisoning • Drugs • Infection: viral and non-viral • Alcohol • Inadequate perfusion • Fatty liver • Autoimmune • Metabolic • Tumours and metastases

Causes of liver disease

• Inadequate intake o Malnutrition (especially alcoholism) o Malabsorption o Total parenteral nutrition (iv) • Renal loss o Diuretic phase of Acute Tubular Necrosis o Hypercalcaemic states o Drugs - Antibiotics - gentamicin / carbenicillin - Chemotherapy - cisplatin - Diuretics - FK506 (Tacrolimus) • GI loss (diarrhoea) • Redistribution into cells o Refeeding syndrome • Spurious causes: EDTA contamination-->can cause falsely low magnesium

Causes of magnesium depletion

o HIV/AIDS—sometimes even with antiretroviral therapy, T-cell immunity is important to prevent mucosal candidosus o Antibiotic use - suppresses normal bacterial flora, less competition for yeasts o Head and Neck cancer - radiotherapy and chemotherapy affect salivary secretions o General debilitation in hospitalised patients - increases colonisation and risk of oral disease

Causes of oral canidida

• Poor intake o Malnutrition o Malabsorption o Alcoholism • Excess losses o Hyperparathyroidism o Diarrhoea o Renal tubular damage o Diabetes (diuresis) • ECF / ICF redistribution - like potassium o Refeeding syndrome o Alkalosis

Causes of phosphate deficiency

obstruction of the bile duct with gallstones, biliary stricture, cancer e.g. cholangiocarcinoma, head of pamcreas tumour Cholangitis

Causes of post hepatic jaundice

o Haemolysis e.g. rhesus incompatibility o Ineffective erythropoiesis e.g. spherocytosis

Causes of pre-hepatic jaundice

Pathology is due to parathyroid Adenoma, carcinoma, and hyperplasia of the parathyroid gland. Sporadic or familial

Causes of primary hyperparathyroidism

After prolonged secondary hyperparathyroidism Usually in CKD

Causes of tertiary hyperparathyroidism

o An autoimmune chronic inflammatory disorder associated with diffuse enlargement and thyroid autoantibodies. o Much more common in females than males o Peak age 59 years. o Diffusely enlarged non-tender gland. o Serum thyroid antibodies elevated. o Lymphocytic infiltration of thyroid parenchyma, often with germinal centre formation. o Many patients become hypothyroid-->so they are at 80-fold increased risk of thyroid lymphoma. o Increased risk of papillary carcinoma of the thyroid.

Chronic lymphocytic thyroiditis (Hashimoto's)

o Antifungal - Azoles (eg clotrimazole, fluconazole) o Terbinafine - Inhibit synthesis of ergosterol - A component of fungal cell membranes - But not human or bacterial cells o Amphotericin B (and nystatin) - Bind to ergosterol causing physical damage to the membrane

Cell membrane agents

Beta cells Hypoglycaemia

Cell type and clinical findings of insulinoma syndrome

δ cell (delta cell) Somatostatinoma syndrome Causes: diabetes, cholelithiasis (formation of gallstones), hypochlorhydria (low HCl secretion in the stomach)

Cell type and clinical findings of somatostatinoma

G cells Causes Zollinger-Ellison syndrome Causes peptic ulcer and diarrhoea

Cell type and clinical syndrome and findings of gastrinoma

Alpha cells Stomatitis, rash, diabetes, weight loss

Cell type and clinical syndrome of glucagonoma syndrome

PP cells

Cell type of pancreatic polypeptide pancreatic endocrine neoplasm (PP-cell PEN)

skin and soft tissue infection most frequently caused by gram positive cocci like staph aureus and strep pyogenes

Cellulitis

• Criteria that give an indication of the likelihood of a sore throat being due to bacterial infection, criteria are: o Tonsillar exudate o Tender anterior cervical lymphadenopathy o Fever above 38 degrees o Absence of cough • If 3 or 4 centor cirteria are met = positive predictive value is 40-60% • Absence of 3 or 4 of the Centor criteria has a fairly high negative predictive value of 80%

Centor criteria

Meningitis Encephalitis Brain abscess

Central nervous system infections

Host factors Opportunity Bacterial factors

Certain bacteria cause infection based on 3 factors

Pruritus , mild discomfort, erythematous external canal that is usually devoid of wax. Often bilateral. White keratin debris may fill the ear canal and over time the canal wall skin may become thickened narrowing the external ear canal. A common cause of chronic OE is allergic contact dermatitis (e.g. from chemicals in cosmetics or shampoos). Generalised skin conditions such as atopic dermatitis or psoriasis can also predispose to chronic OE Treat underlying cause

Chronic otitis externa

• Progressive inflammatory disorder in which parenchyma of pancreas is destroyed and replaced by fibrous tissue • Irreversible destruction of the exocrine tissue, followed by destructions of the endocrine tissue • Leads to malnutrition and diabetes

Chronic pancreatitis

Progressive loss of both islet cells and acinar tissue • Presentation: o Abdominal pain o Malabsorption o Impaired glucose tolerance o Alcohol often an important factor • Malabsorption often presenting feature • Tests of exocrine function i.e. amylase/lipase of NO value except during acute exacerbations

Chronic pancreatitis presentation

o Mild disease Typical vesicles: most have had o Severe chicken pox: Fulminant disease o Can get into lungs and can cause meningitis o Haemorrhagic lesions

Chicken pox

o Chronic obstructive pulmonary disease o Chronic respiratory symptoms, cough, wheezing, breathlessness, chest pain o Consolidation, cavitation on chest CT o Positive culture of Aspergillus from sputum and BAL o Positive for Aspergillus IgG

Chronic pulmonary aspergillosis

Directly cytotoxic Inflammatory cytokine production Cause general inflammation and end-organ damage

Describe autoreactive T cells

Rituximab

Chimeric monoclonal antibody against CD20- B cell surface used for the treatment of chemotherapy resistant Diffuse Large B Cell Lymphoma?

3-10% of Community Acquired Pneumonia cases in adults Causes mild pneumonia or bronchitis in adolescents & young adults Incidence highest in the elderly - may experience more severe disease

Chlamydophila pneumoniae

One of the atypical organisms that causes pneumonia Associated with exposure to birds Consider in those with pneumonia, splenomegaly & history of bird exposure May also have rash, hepatitis, haemolytic anaemia, reactive arthritis

Chlamydophila psittaci

• Malignant tumour of bile duct cells • May be due to chronic inflammation o PSC: primary sclerosing cholangitis liver fluke: Clonorchis sinensis: chronic illness • May be: central/ hilar or peripheral • Aggressive, difficult to resect especially at the hilum of the liver • Firm and hard tumours

Cholangiosarcoma

an acute inflammation of the bile duct characterized by pain in the upper-right quadrant (right hypochondrium) of the abdomen, fever, and jaundice Charcot's triad is fever, abdominal pain and jaundice, only 75% of patients have all 3 findings o Cholestatic pattern of liver test abnormalities, with elevations in: o serum alkaline phosphatase (ALP) o gamma-glutamyl transpeptidase (GGT) o bilirubin (predominantly conjugated) o Colonic bacteria: Enterobacteriaceae principally, and Enterococcus spp) o 2 to: Stones, stenosis, stents, surgery and cancer

Cholangitis

Cholangitis--inflammtion of cystic duct (empties into gall bladder) Cholecystitis--inflammation of bile duct

Cholangitis/Cholecystitis

inflammation of the gallbladder Associated with abdominal pain, fever, history of fatty food ingestion one hour or more before the initial onset of pain Elevation in serum total bilirubin and alkaline phosphatase concnetrations are not common in uncomplicated acute cholecystitis Murphy's sign will be positive Normally associated with gall stones, which do not have their own blood support so cannot have an immunological response to be removed so this results in infection

Cholecystitis

o Mode of action: - Inhibition of β-1,3-glucan synthase - Construction of severely abnormal cell wall o Examples: - Anidulafungin - Caspofungin - Micafungin

Describe the mode of action of echinocandins (antifungals) and give 3 examples

Herpes simplex Cytomegalovirus

Chronic (generally DNA) viruses: latent with or without recurrences

UK prescribed occupational disease in coal miners since 1992 Chronic bronchitis &/or emphysema >20 years underground work Compensation depends on degree of disability & smoking history No CXR or history of dust exposure needed

Chronic bronchitis and emphysema in coal miners

Cough & sputum for 3 months in each of 2 consecutive years Site: Bronchus Cause : Chronic irritation Smoking & air pollution Middle aged & old 1 in 20 of >65yr consult g.p. per year

Chronic bronchitis features

Pathology: Mucus gland hyperplasia and hypersecretion, secondary infection by low virulence bacteria, chronic inflammation Chronic inflammation of small airways of the lung causes wall weakness & destruction thus centrilobular emphysema

Chronic bronchitis pathology

• Inflammation of the gallbladder • Due to chemical or bacterial causes • Over time causes fibrosis, ulceration of gallbladder • Clinical features: pain (RUQ), fever, jaundice • Diagnosis: USS (ultrasound scan) only 25% are visible on x-ray • Treatment: cholecystectomy

Chronic cholecystitis: complication in the gallbladder

o Clear cut edges overhanging the base o Extensive granulation and scar tissue at ulcer floor o Scarring often throughout the entire gastric wall with breaching of the muscularis propria o Bleeding

Chronic gastric ulcer histology

Appears as a patchy, diffuse inflammation of the mucosal lining of the stomach. Appears to be associated with an increased risk for gastric cancer • Autoimmune o Anti-parietal and anti-intrinsic factor antibodies • Bacterial infection (Helicobacter pylori) o Majority have no disease, no symptoms o 2-5% have gastric ulcers o 10-15% have duodenal ulcers o increased risk of gastric cancer and MALT lymphoma • Chemical Injury: NSAIDS, bile reflux, chronic use of alcohol = direct injury

Chronic gastritis

X-linked mutation affecting NADPH oxidase causing dysfunctioning neutrophils and oxidative burst • Granuloma: collection of macrophages • Stops the NADPH complex • Recurrent abscesses: lung, liver, bone, skin, gut (liver abscesses = rare) • Women typically carriers, men usually infected • Unusual organisms e.g. Staphylococcus, Klebsiella, Serretia, Aspergillus, Fungi • Rx: haemopoeitic stem cell transplant, antibiotics • Tests rely on REDUCTION: gain of electron (chemical changes when gains a released electron, in CGD then do not get a reduced DHR • Measure dihydrorhoadamine reduction using flow cytometry • Nitro blue tetrazolium dye reduction: healthy neutrophils should go purple

Chronic granulomatous disease

diseases that cause the lung tissue to become difficult to expand (stiff, decrease compliance), (injury-inflammation-scarring).

Chronic interstitial lung disease

limited interactions Reduce excretion of methotrexate

Interaction of pencillins and beta lactams

Deifinitive host Intermediate host Paratenic host

Classes of host

Symptoms of UTI

Classic UTI symptoms in older children Dysuria, frequency, urgency, small-volume voids, lower abdominal pain. Infants with UTIs have nonspecific symptoms Fever, irritability, vomiting, poor appetite

Impetigo

Classically ruptured vesicles with honey-coloured crusting May be bullous More common in pre-existing skin disease Very contagious, rapid spread Commonly starts around face/mouth Rx. Topical antibiotics or oral Flucloxacillin Advice re nursery/school

Nematodes and platyhelminths

Classification of parasites helminths

o Unlike follicular carcinoma, there is a significant incidence of cervical lymph node metastases o Common haematogenous sites—bone, liver and lung

Clinical behaviour of hurthle cell carcinoma

Pulmonary tuberculosis is the most common presentation Chronic productive cough, haemoptysis Weight loss, fever, night sweats Can disseminate (miliary TB) or affect almost any other organ

Clinical presentation of mycobacterium tuberculosis

Breast triple assessment

Clinical examination--history and physical examination Radiological examination--ultrasound and mammography Pathological examination--core cut biopsy and fine needle aspiration cytology

o Enteropathy-associated T-cell lymphoma (small bowel lymphoma) o Small intestinal adenocarcinoma o BEWARE!!!! Symptoms despite Gluten Free Diet: known coeliac disease but not responding well to diet then have to investigate that have not developed a cancer

Clinical features and associations of coeliac disease

• Bone pain • Bone deformity • Fractures: more bone but not strong • Arthritis: stresses on the joints especially the adjacent joints • Cranial nerve defects if skull affected: Hearing and vision loss • Risk of osteosarcoma (bone cancer) • Most commonly affects pelvis, femur and lower lumbar vertebrae • Less common than it used to be, but do not know why

Clinical features of Paget's bone disease

Hypertension Sweating, pallor Panic attacks Headaches Abdominal pain nothing?

Clinical features of Phaeochromocytoma

Asymtpomatic 80% Crampy pain--biliary colic

Clinical features of gallstones

Causes (THINK MALABSORPTION) Diffuse bone pains which are usually symmetrical Muscle weakness Bone weakness Adult population that are at risk: Nursing home residents/elderly Asian population (Hijab/burka wearing) Malabsorption

Clinical features of osteomalacia

Trismus--minor spasms of the jaw Induration--hardening of soft tissue Swelling below the angle of the mandible Medial bulging of the pharyngeal wall Systemic toxicity with fever and rigors

Clinical features of parapharyngeal space infections

Lung Migration: Loefflers syndrome- dry cough, dyspnoea, wheeze, haemoptysis, eosinophilic pneumonitis Intestinal Phase: Malnutrition Malabsorption Migration - into hepatobiliary tree and pancreas Intestinal obstruction Worm burden

Clinical manifestations of Ascariasis

• Incubation 2-10 days (usually 7 days) • Watery diarrhoea with mucus (no blood) • Bloating, cramps, fever, nausea, vomiting • Usually self-limiting • Can be severe in very young, very old and immune compromised • 60% HIV patients infected go on to chronic infection so can lose up to 25 litres of fluid per day Those at risk: Human-human spread: • Regular users of swimming pools (can be resistant to chlorine) • Child care workers and parents • Nursing home residents/carers • Healthcare workers • Travellers Animal-human spread: • Backpackers, campers, hikers • Farm workers • Visitors to farms/petting zoos • Consumers of infected dairy products

Clinical manifestations of cryptosporidosis

• GI: • Vomiting, diarrhoea, oral symptoms. • Respiratory (upper and lower): • Rhinitis and bronchospasm. • Cutaneous: • Urticaria and angioedema. • Role of food in atopic dermatitis is unclear. • Anaphylaxis.

Clinical manifestations of food allergies

Symptoms usually last 1-3 weeks: • Diarrhoea • Abdominal pain • Bloating • Nausea and vomiting

Clinical manifestations of giardiasis

• Cysts: 70% liver and 20% in the lung • May remain asymptomatic for years • Mass effect • Secondary bacterial infection • Cyst rupture-hypersensitivity

Clinical manifestations of hydatid disease

- Symptoms related to hypercalcaemia (as described) o Renal disease (nephrolithiasis, chronic kidney disease) o Bone disease (osteoporosis, osteitis fibrosa cystica) o Proximal muscle wasting o Bone pain o Subperiosteal bone resorption typically middle phalanges, clavicles, skull, long bones

Clinical manifestations of primary hyperparathyroidism

Swimmer's itch-->allergic immune reaction with itchy raised papules Katayama fever Chronic schistosomiasis Effect of eggs in distant sites e.g. spine and lung Urinary (S.haematobium): -Hameaturia -Bladder fibrosis and dysfunction Squamous cell carcinoma bladder Hepatic/Intestinal (S. mansoni; S. intercallatum, S. japonicum; S. mekongi) • Portal hypertension • Liver cirrhosis • Abdo pain • Hepatosplenomegaly

Clinical manifestations of schistosomiasis

o Chronic relapsing disease o Affects all levels of GIT from mouth to anus o Diarrhoea: may be bloody o Colicky abdominal pain o Palpable abdominal mass o Weight loss/failure to thrive: especially children o Anorexia: loss of appetite o Fever o Oral ulcers o Peri-anal disease o Anaemia

Clinical presentation of Crohn's disease

Usually influenza produces uncomplicated disease: Fever, headache, myalgia, dry cough, sore throat Convalescence i.e. time taken to recover takes 2-3 weeks

Clinical presentation of influenza

alters phenytoin concentrations

Interaction of quinolones e.g. ciprofloxacin

o Diarrhoea > 66 % with urgency/tenesmus (feeling of fullness in rectum) o Constipation 2 % o Rectal bleeding > 90 % o Abdominal pain 30-60 % o Anorexia o Weight loss 15-40 % o Anaemia • Progressive disease, only affects the large bowel so if you remove the colon (drastic) you would cure UC • UC is continuous inflammation

Clinical presentation of ulcerative colitis

o Acute onset cramping abdominal pains o Urge to defaecate o Bloody diarrhoea/ rectal bleeding o Symptoms improve within 48hrs o Complete recovery 1-2wks o 20% require surgery for colonic infarction

Clinical symptoms of ischaemic coltiis

Unknown cell type Verner-Morrison syndrome Causes diarrhoea, hypokalaemia, achlorhydria

Clinical syndrome and clinical findings of VIPoma

• Positive ANCA is extremely useful in suggesting the diagnosis in the proper clinical setting. • Histopathology remains the gold standard for diagnosis in most cases. • Negative ANCA assays do not exclude AASV (vasculitis) since 10-50% of patients may be ANCA negative. Put it in the clinical context. • Persistence of ANCA in the absence of clinical indications of active disease does not indicate a need for continued treatment. • Re-emergence of ANCA positive in a patient who was ANCA negative whilst in remission suggests a risk of disease flare. The temporal correlation between the return of ANCA and a disease flare is poor

Clinical uses of Anti-neutrophilic cytoplasmic antibodies (ANCA) testing:

Prevent organ and allograft rejection in transplantations Have immunosuppressant functions so can be used to treat autoimmune diseases

Clinical uses of calcineurins and Rapamycins

Shortness of breath Infective symptoms Hypoxia Shortness of breath Dyspnoea (difficulty or laboured breathing)

Clinically apparent signs of pathology in the lung

Main subdivisions of haematology

Coagulation Malignant Non-malignant Transfusion

Sensitivity to gluten. Gluten leads to villous atrophy which causes malabsorption. • known as coeliac sprue or gluten sensitive enteropathy • immune mediated enteropathy • ingestion of gluten containing cereals o wheat, rye or barley o genetically predisposed inds • fairly common, estimated prevalence of 0.5-1%

Coeliac disease

• Inflammation of the colon • usually mucosal inflammation but occasionally transmural i.e. occurring across the entire wall of a blood vessel or organ (eg. Crohn's disease) or predominantly submucosal/muscular (eg. eosinophilic colitis) • divided into acute (days to a few weeks) and chronic (months to years)

Colitis classification

Crohn's disease which shows the colon that has skip lesions i.e. parts of normal bowel, then diseased bowel so inflammation is discontinuous

Colon that has Crohn's disease

Patients with bowel cancer can present with a bacteraemia caused by Streptococcus bovis (now re-named S. gallolyticus). S. bovis bacteraemia is also associated with endocarditis This is the growth of bacteria on heart valves Disease association with endocarditis and bowel cancer

Colonic malignancy

adenocarcinoma of the colon or rectum, or both • 2nd or 3rd commonest cancer causing mortality after bronchus, breast and prostate • lifetime risk 1 in 18-20, 5% • most bowel cancers = sporadic, do not know what caused them • family history 15-20% do not know why, but weak genetic risk, some genes that are interacting and make them more predisposed • inherited strong risk: FAP or HNPCC (lynch syndrome) 1% and 5% • estimated prevalence in UK: 77,000 (2000) • UK incidence: 35,300 (2000) • Mortality in UK: 16,220 (2002)

Colorectal cancer

• Overall prevalence: 3.7% • Prevalence in pancolitis: 5.4% • Risk of CRC at 10yrs: 2%, 20yrs: 8%, 30yrs: 18%

Colorectal cancer risk in UC

• Direct invasion of adjacent tissues • Lymphatic metastasis (lymph nodes) • Haematogenous metastasis (liver & lung, sometimes skin and bone) i.e. can invade blood vessels • Transcoelomic (peritoneal) metastasis: through abdominal cavity • Iatrogenic spread e.g. needle track recurrence or port site recurrence: needle through the bowel or laproscopic, tube through abdominal wall then can be spread all the way through the abdominal wall

Colorectal cancer spread

benign tissue growths on the mucous membrane lining the large intestine and rectum; adenomatous types are precancerous and likely to develop into malignancy • Mucosal protrusion • Solitary or multiple: polyposis • Pedunculated, sessile or flat • Small or large • Due to mucosal or submucosal pathology or a lesion deeper in the bowel wall • Neoplastic. Hamartomatous, inflammatory or reactive • Benign or malignant • Epithelial or mesenchymal (supporting connective tissue)

Colorectal polyps

Treatment of cervical intraepithelial neoplasia

Colposcopy-->examination of cervix with a low powered stereoscopic microscope The cervix is often painted with acetic acid to highlight potentially abnormal epithelium which can be resected under local anaesthetic with a diathermy loop. This is then subjected to histopathological examination to guide further treatment. Large loop excision of the transformation zone (LLETZ)

Fibroadenoma

Common benign breast tumor. Unilateral, solid, well-defined mass that does not invade surrounding tissue. Common, usually in women 20-30 years More common in Afro-Caribbean women Mobile, painless, well defined breast lump Usually found as a lump - asymptomatic. Rarely undergo infarction. Radiology : Well defined homogenous, hypoechoic mass on U/S. Rx : Surgical excision. Some may recur.

Upper respiratory tract infections in children

Common cold Acute tonsilitis Acute otitis media

Spine Neck of femur Wrist

Common sites of fracture

Define endometrial cancer

Commonest gynae cancer with increasing incidence there are two types Type 1 cancers are the most common type. They are usually endometrioid adenocarcinomas, and are linked to excess oestrogen in the body. Type 2 cancers include uterine serous carcinomas and clear cell carcinomas.

An inherited multiorgan disorder of epithelial cells affecting fluid secretion in exocrine glands and the epithelial lining of the respiratory, gastrointestinal and reproductive organs Mostly affects Caucasians Incidence 0.4 per 1000 live births Autosomal recessive inheritance

Cystic fibrosis features

This can give false positives and false negatives

Comparing diseased groups

• In non-competitive assay, there are two antibodies, the capture antibody which can bind to the protein and a detecting antibody which can also bind to the protein • However, in competitive assay, the protein must compete for the binding site of one type of antibody—a capture antibody

Competitive vs non-competitive assays

• Take a well and add the cells from the donor, T cell in and class 1 molecules no class two on and other proteins e.g CD4 and add serum that is going to have kidney • Then serum may have antibodies • Then add complement and have lysis of the cell • Can pick up cross match • Do the assay, if neg then transplant go ahead • B cells slightly different as class two

Complement Dependent Cytotoxicity Test (CDC) (older method)

• Hereditary, rare • Encapsulated bacteria: need complement to help kill organisms • Example: C5-8 then Neisseria meningitidis: important • Frequent, serious S. pneumoniae infections as poor quality opsonisation • Example: meningitis layers of pus around the brain, intracellularly organisms: strap neg cocci within neutrophils of the CSF

Complement deficiency

3 pathways: Classical, alternative and mannose-binding lectin Final common pathway to make: Membrane attack complex (C5b-C9) o Non-immunoglobulin proteins, that are important in the immune system for - Cell lysis (kill invading bacterium) - Control of inflammation - Stimulate phagocytosis o A sequence of events activates complement proteins • Complement should lyse foreign cells if the foreign cells are covered in antibody o Will trigger the classical complement cascade

Complement pathway

More than one intermediate host

Complex indirect life cycle

• Infection that extends beyond the hollow viscus of origin into the peritoneal space and is associated with ether abscess formation or peritonitis o More severe spectrum of disease • Important to make distinction between complicated and uncomplicated: complicated need rapid surgical intervention and treatment: histopathologists and surgeons work together to determine • Complicated intra-abdominal infection: o Perforated cholecystitis o Perforated diverticulitis o Perforated appendicitis o Perforated gastric/ duodenal ulcer o Post operative anastomotic leak/ latrogenic o Colonic perforation after C diff infection o Ischaemic colon or malignancy with perforation of bowel o Colonic fistula communication with the peritoneal space o Abscess in solid organ communicating with the peritoneal space e.g. liver abscess • Uncomplicated Complicated intra-abdominal infection or inflammation o Cholecystitis o Diverticulitis o Appendicitis o Gastric/duodenal ulcer o C diff infection

Complicated intra-abdominal infection

• Toxic megacolon • Perforation • Fistula: do not occur in UC, Crohn's ulcers all the way through the bowel wall = development of fistula due to sticking to other organs e.g. urinary bladder, faeces when urinate, vagina • Stricture: common, uncommon in UC, matches pattern (UC = superficial inflammation, Crohn's = inflammation all the way through the bowel = narrowing of the lumen) • Haemorrhage • Carcinoma: risk of large and small bowel cancer • Short bowel syndrome: repeated resection: not enough bowel to maintain nutrition, complication due to treatment of Crohn's disease, removing too much small bowel

Complications of Crohn's disease

1. Toxic megacolon (can rupture) 2. Carcinoma (biggest complication) o UC just affects the bowel, no more of GI, remove bowel + stoma = cured o Toxic megacolon and perforation - Perforation = more restrictive - Very distended colon >6cm - toxic megacolon more than 6metres long: medical and surgical treatment needed immediately o Haemorrhage o Stricture: rare-->stricturing in someone with colitis is usually Crohn's and is rarely ever UC o Carcinoma

Complications of UC

Shock due to peripancreatic hemorrhage, Pancreatic PSEUDOcyst - just lined by fibrous tissue surrounding the liquefactive necrosis and enzymes.(Causes persistent elevation of amylase), DIC and ARDS(enzymes can activate coagulation, can also destroy lung tissue if they get into blood) • Intravascular coagulopathy • Haemorrhage • Pseudocysts: collections of pancreatic juice secondary to duct rupture o A pseudocyst has no epithelial lining • Many of systemic features are related to the release of toxic enzymes, cytokines and other mediators into circulation resulting in activation of the systemic inflammatory response

Complications of acute pancreatitis

Pneumonia, septicaemia, metastatic infection, amyloid

Complications of bronchiectasis

• Malabsorption of fat (lack of lipases) o Steatorrhoea o Impairment of fat soluble vit absorption -A,D, E and K o Diarrhoea, weight loss and cachexia • Diabetes (late feature) • Pseudocysts (10% patients) • Stenosis of common bile duct/duodenum • Severe chronic pain • Mortality rate - nearly 50% within 20-25 years of disease onset

Complications of chronic pancreatitis

• Cirrhosis o Defined histologically as a diffuse hepatic process characterised by fibrosis and the conversion of normal liver architecture into structurally abnormal nodules o Liver cells still present, but portal vein blood bypasses the sinusoids so the liver cells cannot perform their functions o Pressure inside the liver incs = portal hypertension • major risk factor for hepatocellular carcinoma = cirrhosis • hepatocellular carcinoma = one of the commonest cancers worldwide, inc rapidly in UK • Cirrhosis

Complications of cirrhosis

o Obstruction at neck: pain due to obstruction in the biliary tree o Obstruction: common = jaundice o Chronic cholecystitis o Perforation o Obstruction at pancreatic level: pancreatitis = more severe complication - When a gall stone gets to the pancreas it stops the pancreas from releasing its secretions - Chronic pancreatitis can cause diabetes

Complications of gallstones

1. ASYMPTOMATIC 50+% 2. ARTERIAL HYPERTENSION 5-48% 3. PSYCHIATRIC PROBLEMS 14-20% 4. HYPERCALCEMIA 20% 5. DECREASED RENAL FUNCTION 4-14% 6. OSTEOPOROSIS 12% 7. HYPERPARATHYROID BONE DISEASE 8% 8. HYPERCALCEMIA SYMPTOMS 8% 9. UROLITHIASIS 4-7%

Complications of hyperparathyroidism

• Ulceration: -->gives pain o wearing through the tissue layers • Haemorrhage: o involve the blood vessels can be life threatening • Perforation: o ulceration through to the muscle layer and leakage of contents into thorax • Benign structure: --> due to fibrosis in oesophagus o segmental narrowing: ulceration and then the oesophagus heals = scar tissue, have to rule out oesophageal cancer • Barrett's oesophagus

Complications of reflux oesophagitis

• Phagocytic cells: • Neutrophils - eat and destroy pathogens. • Macrophages - also produce chemokines to attract other immune cells. • Dendritic cells - also present antigen to the adaptive immune system. • Histamine producing cells: • Mast cells, basophils, eosinophils - produce histamine and other chemokines and cytokines. • Vasodilation and attract other immune cells. • Defence against parasites, wound healing, but also allergy and anaphylaxis. • Complement: • Directly attacks pathogens via alternative and lectin pathways. • May be activated by adaptive immune system via antibodies. • Cytokines: • Signal between different immune cells (e.g. innate to adaptive, adaptive to innate). • Chemokines: • Attract other immune cells to sites of inflammation l

Components of innate immune system inflammation

Outer cortex and inner medulla

Components of the adrenal gland

scleroderma

Condition characterised by Raynaud's phenomenon, skin thickening and tightening in fingers and face with fibrosis of the internal organs?

Coeliac disease

Condition in which there are IgA antibodies to tissue tranglutaminase (TTG) with villous atrophy of the duodenum

myasthenia gravis

Condition in which there are antibodies to acetylcholine receptors?

Lynch syndrome/HNPCC

Condition in which there is increased susceptibility to developing colorectal cancer due to mutations in DNA mismatch repair genes

o Usually has to be given lifelong o Antiviral toxicity can be a problem o Maintaining good adherence can be challenging o Need to avoid emergence of resistance

Conditions of treatment of chronic virus infections

ohyperaldosteronism, primary & secondary W>M, 30-50yrs o excess production of the hormone aldosterone by the adrenal cortex leading to low renin levels. Controlled by renin-angiotensin system. o Aetiology include adrenal cortical hyperplasia, adenoma and familial hyperaldosteronism o Symptoms and signs - high BP, headache, muscular weakness, muscle spasms, excessive urination, cardiac arrythmias.

Conn's syndrome

• Systemic lupus erythematosus. • Scleroderma. • Polymyositis. • Sjogrens syndrome.

Connective tissue diseases examples

o Demographic details - from request o Results - from laboratory analysis o Reference ranges - from scientific knowledge o Comments & Advice - from experience o Human computer knowledge bases

Contents of a lab report

• Chemical treatment to kill snail intermediate hosts • Chemoprophylaxis • Avoidance of snail infested waters • Community targeted treatment, education and improved sanitation •

Control (prevent spread) of schistosomiasis

General advice about prevention of STIs Use of barrier contraceptive methods if sexually active (prevent sperm from entering cervix)

Control methods to prevent the spread of trichomoniasis

Regularly worm dogs to reduce egg production Hand hygiene Safe disposal of animal carcasses/products of conception

Control spread of hydatid disease

Insecticide spraying in homes • Larvicidal spraying on breeding pools • Filling in of breeding pools • Larvivorous species introduced into mosquito breeding areas • Use of insecticide-impregnated bed nets • Chemoprophylaxis-->preventative drugs • Vaccine??

Control spread of malaria

• No vaccine available • Hygiene measures • Boiling water

Control to prevent spread of giardiasis

Human-human: • Hand hygiene • Filter or boil drinking water • Isolate symptomatic patients in a healthcare setting • Ensure symptomatic patients are kept away from school Animal-human: • Pasteurise milk and dairy product • Boil or filter drinking water if camping

Control to reduce spread of cryptospiridosis

Localised: Impetigo Erysipelas Cellulitis Severe/extensive-->necrotising fascitis Diabetic foot infection

Examples of skin and skin structure infections

Gram positive bacilli A number of these type of bacteria are commensals of the skin and upper respiratoty tract occasional opportunistic infections are associated with devices and trauma

Corynebacterium species

Affects any part of the GI tract • Crohn's is also progressive so those who initially only had colonic disease may later get e.g. small bowel disease • Ileocolic: 30-55%: ileum and caecum • Small bowel: 25-35% • Colonic: 15-25%: colon • Peri-anal/ ano-rectal: 2-3%: anus and rectum • Gastro-duodenal: 1-2%: stomach and duodenum

Crohn's disease distribution

anus

Crohn's disease most commonly affects

Cryoprecipitate

Cryoprecipitate is extracted from FFP, during the thawing process. Contains fibrinogen, von Willebrand, factor VIII, factor XIII Therapeutic dose :10-15 ml/kg (6-10 units) It is mainly used as a concentrated source of fibrinogen in acquired coagulopathies i.e massive haemorrhage, disseminated intravascular coagulation (DIC) Treatment of bleeding: maintain fibrinogen at more than 1.5g/L Prevention of bleeding: maintain fibrinogen >1g/L

A genetic disorder that occurs in people with two copies of a certain recessive allele; characterized by an excessive secretion of mucus and consequent vulnerability to infection; fatal if untreated. • CF affects 1in 2,500 newborn infants in UK o Common disease associated with malnutrition • Cystic fibrosis transmembrane regulator (CFTR) protein • cAMP dependent chloride channel • localises to the apical membrane of secretory and absorptive epithelial cells within the: o airways o pancreas o liver o intestine o sweat glands o vas deferens

Cystic fibrosis

o Establishes the presence of a micro-organism at a particular site o Cultivable organisms only o Allows the use of empiric and targeted antimicrobial therapy o Provides epidemiological and typing information o Is usually slower than direct detection

Cultures, uses and limitations:

Compatibility testing 'cross matching' (only for RBC transfusions)

Final test before transfusion of RBCs Donor red cells of the correct ABO and Rh group and antigen negative for the antibodies detected in screen are selected from the blood bank

Rarely described in immunocompetent hosts Can cause severe illness in transplant recipients and HIV patients (uncommon) Tests: Chest-Xray, Broncho-alveolar lavage & viral load PCR Treatment: Supportive, anti-viral (e.g. ganciclovir) & consider immunosuppression reduction (transplant pts).

Cytomegalovirus pneumonia Tests Treatment

o Vasculitis (Wagner's, Churg Straus Syndrome) o SLE

Cytotoxic clinical uses in cyclophosphamide

o Autoimmune diseases (SLE, vasulitis, IBD) o Allograft rejection

Cytotoxic clinical uses of azathioprine and mycophenolate mofetil

o Rheumatoid Arthritis, Psoriatic Arthritis, Polymyositis, vasculitis o Graft versus Host Disease in Bone Marrow Tranplantation

Cytotoxic clinical uses of methotrexate

pneumonitis

Cytotoxic side effect of methotrexate

o Bone marrow suppression o Gastric upset o Hepatitis o Susceptibility to infections

Cytotoxic side effects of of antimetabolites and cytotoxic drugs

o 5 fluorocytosine (5FC) is a fungal DNA inhibitor, developed as a putative anti-cancer drug o Selectively taken into fungal cells by a fungal enzyme (cytosine permease) o Selective toxicity poor o Not used very much

DNA synthesis inhibitors in fungi

quinolones and fluroquinolones: o Inhibit one or more of two related bacterial enzymes DNA gyrase and topoisomerase IV Involved in remodelling of DNA during DNA replication o Examples Nalidixic acid, ciprofloxacin, levofloxacin o Quinolones are effective against bacteria only

DNA synthesisi inhibitors

what is lymphopenia? When does it occur?

Decreased numbers of lymphocytes e.g. post bone marrow transplant

What is neutropenia and when does it happen?

Decreased numbers of neutrophils This may be the side effect of a drug e.g. suppressant

Horner's syndrome can sometimes be caused by a tumour in the lung. What are the symptoms?

Decreased pupil size Drooping of the eyelid--ptosis Decreased sweating on the affected side of the face--anhidrosis

Spread of infection can be from the oral cavity, face, or superficial neck to the deep neck space via the lymphatic system. May have a rapid onset and can progress to life threatening conditions Peritonsillar abscess (quinsy) Acute suppurative parotitis Submandibular space infections (Ludwing's angina) Pretracheal space infections Prevertebral space infections Parapharyngeal space infections Retropharyngeal and danger space infections

Deep neck space infections

This occurs in agammaglobulinaemia Bruton's tyrosine kinase is needed for B cell signalling and b cell maturation B cell maturation is not completed in the bone marrow

Defect in Brutons tyrosine kinase

• loss of antibody secretion. • Usually leads to recurrent bacterial infection with pyogenic organisms. • Treat with antibiotics then i.v IgG for life. • Most are very serious • Some less serious e.g IgA deficiency. o 1 in 5-700 o Some completely well o Higher risk of autoimmune diseases e.g. coeliac

Defects in B cells

Usually more severe since B cells also need T cell help Even if there are B cells, they don't function Symptoms are recurrent infection with opportunistic infections, bacteria, viruses, Fungi (candida), protozoa (pneumocystis). Types SCID Others: e.g. DOCK8 deficiency

Defects in T cells

Recurrent pneumonia, poor inflammatory response

Deficiency in PRR of phagocyte example of IRAK4 result in

Chronic grnulomatous disease

Deficiency in the function of phagocytes causes

bacterial meningitis

Defieicny in complement causes

Establishing a reference range for haematological samples

Define the reference population Reference population should be relevant to the test population Consider if separate ranges are required for adults versus children, men versus women, and so forth. Determine the expected range of interindividual variation the set of values for a given test that incorporates 95% of the normal population why 95%? Arbitrary convention. determined by collecting data from vast numbers of laboratory tests 95% of results fall within the reference range

the host in which the sexual reproduction of a parasite takes place This is usually a human The host harbours the adult stage of the parasite

Definitive host

Localized destruction of the hard dental tissues by plaque bacteria Caries Pulpitis Periapical abscess Not clear which bacteria cause pulipitis and periapical abscess but it is likely they are oral commensals, e.g. Streptococci and anerobes Denal x-rays and examinations aid diagnosis

Dentoalveolar infections

Lack of self-renewal

Depleted stem cell pool Generation of only differentiated progeny OR there can be maintenance of the stem cell pool BUT there is no differentiated progeny

Fibrous and fibroadipose tissue Supports epidermis physically and metabolically Contains blood vessles, nerves and sensory receptors

Dermis

An autoimmune disease that produces antibodies to TSH receptors on the thyroid. Anti-TSH autoantibody Overactivates thyroid-->leads to hyperthyroidism Antibodies stimulate the thyroid

Describe Grave's disease

Destruction of thyroid follicles by autoimmune process Associated with autoantibodies to thyroglobulin and to thyroid peroxidase Leads to hypothyroidism Antibodies destroy the thyroid

Describe Hashimoto's thyroiditis

Epidemiology: 248 million people chronically infected >500, 000 deaths annually Mode of transmission: vertical, sexual, parenteral Clinical course: - Following transmission, acute clinical hepatitis may occur but 90% children and 50% young adults are asymptomatic of acute infection - Hepatitis B is then cleared, or persists and becomes chronic - Risk of chronicity is inversely related to age at infection *** - 90% of hep B infections acquired during pregnancy (perinatally) progress to chronic - vs. 20-50% aged 1-5 years - vs. <5% adult-acquired infections - Over time, chronic hepatitis → cirrhosis → hepatocellular carcinoma

Describe Hep B: Epidemiology Mode of transmission Clinical course

Epidemiology: 170 million people infected worldwide Prevalence in developed countries is low 0.5-2% In the UK, 50% of those who inject drugs have evidence of hep C Mode of transmission: Sharing needles, needlestick injuries, transfusion of contaminated products Vertical and sexual transmission is less common Important clinical syndromes: o After transmission, approximately 25% develop acute clinical hepatitis o 15% will then clear the virus, but 85% will become chronically infected o Over time, chronic hepatitis → cirrhosis → hepatocellular carcinoma

Describe Hep C: Epidemiology Mode of transmission Important clinical syndromes

• Measles: o Epidemiology: - Previously endemic in UK with 2-3 yearly epidemics - Now due to vaccine, occurs in clusters of unvaccinated o Mode of transmission: - Droplet transmission from respiratory route - Highly infectious environment still infectious after 2 hours o Important clinical syndromes: 1. Primary measles - Fever, coryza (inflammation of mucous membrane of nose), cough, conjunctivitis, Koplik's spots on inside of cheek*** - Then maculopapular rash 2. Acute post infectious measles encephalitis (1:1000) - Occurs 7-10 days after acute infection, high mortality rate - Immune-mediated 3. Subacute sclerosing pan-encephalitis SSPE (1: 1000000) - 7-10 years after natural measles infection - Progressive, degenerative and fatal disease of the CNS

Describe Measles: Epidemiology Mode of transmission Important clinical syndrome

it is a neuromuscular autoimmune disease that produces fatigue and muscle weakness. There is a decreased amount of acetylocholine at the myoneuronal junction Autoantibodies are produced which block the acetylcholine receptor Acetylcholine cannot bind so muscle weakness develops, particularly in the eyes

Describe Myasthenia Gravis

• Failure of vitamin B12 absorption (supplements don't do anything). • B12 needs intrinsic factor to be absorbed. In this, an auto-antibody binds to intrinsic factor and stops the B12 from binding

Describe Pernicious anaemia

Lupus • Antibodies against antigens in the nucleus combine with their targets to form immune complexes in the circulation. • Immune complexes deposit in any organ - activates complement and causes inflammation.

Describe SLE

Delayed type hypersensitivity • Immunopathology: • Antigen specific T-cell mediated cytotoxicity. • Clinical features: • Delayed onset 48-72 hours. • Erythema induration. • Test using a patch test. • Common antigen: • Metals. E.g. nickel causing contact dermatitis. • Tuberculin reaction. • Associated diseases: • Contact dermatitis. Transferred with T cells Histology of monocytes and lymohocytes Antigen is tissues and organs

Describe Type IV hypersensitivity

Viral pathogens are simple microorganisms that are not capable of independent existence Need a host cell to survive e.g. red blood cell, a respiratory epithelial cell Steal energy, metabolic intermediates and enzymes from cells to replicate

Describe a viral pathogen

o Affects 70-80% all women at least once during child-bearing years o Pruritis, burning sensation, +/- discharge o Inflammation of vaginal epithelium, may extend to labia majora o Often more florid infections during pregnancy o Approximately 10% of women will suffer from recurrent vulvovaginal candidosis. Probably relates to subtle immune defect o Diagnosis by positive culture in symptomatic patients

Describe candida vulvovaginitis

Results from inflammation of flase diverticuli that typically form in the sigmoid colon of patients consuming low fiber diets. This condition usually presents with left lower quadrant abdominal pain and rectal bleeding • Uncomplicated vs. complicated • Complicated= abscess, fistula, perforation, obstruction

Describe diverticulitis

--Associated with high rate of H, pepsinogen secretion --Feedback inhibition of gastric production is dysfunctional Relative incidence: 3 Age distribution: increases up to 35 years Acid levels are elevated or normal H. Pylori causes a duodenal ulcer 95-100% of the time as H.Pylori predominantly affects the antrum Localisation: affects the bulbus of the duodenum which is the portion of the duodenum closest to the stomach Unlike gastric ulcers, duodenal ulcers commonly affect younger people MAINLY AFFECTS BLOOD GROUP O PATIENTS

Describe duodenal ulcers

Multicellular eukaryotes that have a rigid cell wall made of chitin. They are chemoheterotrophs. They are saprophytes (feed off the dead), parasites, or mutualists. Their method of feeding is absorption. Many fungal cells make hyphae, which are long and filamentous, which then form mycelium. Grow either by hyphae or yeast Reproduce sexually by spore formation or asexually

Describe fungi

o Disease names: - HSV-1, 'cold sores' o Epidemiology: - Exists worldwide, humans are only known reservoir - 80% of UK population experience HSV-1 in their lives o Mode of transmission: - Direct contact with vesicle fluid from lesions - Latency in sensory nerve ganglia*** - Periodic reactivations o Important clinical syndromes: o 1. Vesicles / ulcers to skin or mucous membranes - typically mouth (HSV-1) o 2. Encephalitis - often severe or fatal, HSV-1 = commonest cause of viral encephalitis worldwide

Describe herpes simplex 1

Faecal-oral: virus is shed in the faeces of an infected individual Clinical syndrome: nausea, myalgia (muscle pain), arthralgia (joint pain), fevers then jaundice and right upper quadrant pain (right hypochondrium)--usually self limiting Hep A and E are an endemic in the developing world and are associated with contaminated water

Describe how Hep A and E are transmitted and the clinical syndrome they present with

• General, not antigen specific but can recognise broad classes e.g. bacteria • Rapid speed of onset • Does not alter on repeated exposure • No memory

Describe innate immunity

Epidemiology: - Endemic childhood infection worldwide - Cases peak in temperate climates in winter o Mode of transmission: - Virus is shed in saliva and respiratory secretions - Respiratory droplet transmission - Very infectious o Important clinical syndromes: 1. Acute parotitis - unilateral or bilateral (inflammation of one or both parotid glands) 2. Orchitis-->inflammation of testicles - Affects 20-30% of males with mumps*** - Typically develops 4-5 days after parotitis 3. Meningitis - Occurs in up to 15% of mumps cases - Can lead to meningoencephalitis and sensorineural deafness*** - Prior to MMR vaccine, mumps was one of the commonest causes of viral meningitis

Describe mumps : Epidemiology Mode of transmission Important clinical syndromes

• Affects a single organ. • Autoimmunity restricted to autoantigens of that organ. • Overlaps with other organ specific diseases (not systemic, just different tissues). • Autoimmune thyroid disease is typical.

Describe organ specific autoimmune diseases

Calcium is usually high PTH inappropriately high Low phosphate and high alkaline phosphatase common • Previously used to present with severe hypercalcaemia, and/or symptomatic renal and skeletal disease • Now presentation is much earlier in disease course and is usually asymptomatic • Majority of cases present at >45 years of age • Women twice as likely to be affected compared to men • Inappropriately elevated PTH in the presence of high calcium suggests PHPT

Describe primary hyperparathyroidism

problem with CKD Calcium is normal or low PTH is appropriately high Phosphate is high if due to CKD

Describe secondary hyperparathyroidism

o Primary pathogen o 30-50% of people carry it in the nose o It causes skin/soft tissue infections o Causes bacteraemia/septicaemia (bacteria in the blood) o Osteomyelitis/septic arthritis (infection of the blood) o Causes: - Endocarditis - Pneumonia - UTI - Meningitis

Describe staphylococcus aureus

Commensal pathogen that most people carry on the skin o Gram positive coccus o It is an opportunistic pathogen, i.e. with the right opportunity it can cause infection o Causes infection in association with 'foreign bodies' e.g. intravascular catheters, prosthetic joints, prosthetic cardiac valves o Adheres to plastics/metals using glycocalyx (slime)forming biofilms o This can occur in e.g. a hip replacement, in the time the hip is taken out of the sterile bag and put into the patient's body, it is exposed and bacteria like S. epidermis could adhere to it

Describe staphylococcus epidermitis

• Affects several organs simultaneously. • Autoimmunity associated with autoantigens found in most cells of the body. • Overlap with other non-organ specific diseases. • Connective tissue diseases are typical.

Describe systemic autoimmune diseases

1% of total phosphorus in the body Phosphorus in the blood is either in the organic form or the inorganic form Organic form-->covalently bound i.e. part of a compound bound to carbon e.g. phospholipids at around 70% Inorganic form is around 30%

Describe the distribution of phosphorus in the blood

Anti-viral Nucleoside reverse transcriptase inhibitor Developed in 1965 as an anti-cancer drug In 1985, it was found to inhibit HIV replication

Describe the drug azidothymidine

Double stranded enveloped DNA viruses 9 types known to infect humans Characterised by their ability to establish latency and reactivate

Describe the herpes virus

Usual interstitial pneumonia (UIP) Interstitial chronic inflammation & variably mature fibrous tissue Adjacent normal alveolar walls Similar pattern of fibrosis in collagen vascular disease associated interstitial lung disease and in asbestosis

Describe the histology of idiopathic pulmonary fibrosis

• Normal oesophagus = 25cm long muscular tube o Mostly lined by squamous epithelium (mouth, continuation of skin, non-keratinising to just above the GO junction • Sphincter at upper end = cricopharyngeal • Sphincter at Lower end = gastro-oesophageal junction • Distal 1.5-2cm are situated below the diaphragm and lined by glandular columnar mucosa • The squamo-columnar junction: located 40cm from the incisor teeth Can measure to see if abnormal or normal

Describe the oesophagus

o It weighs 500—1000mg o Consists of two parts: anterior and posterior o 75% of the gland is formed by the anterior lobe which is formed by an outpouching of the oral cavity (Rathke's pouch) (Adenohypophysis) o 25% of the gland is formed by the posterior lobe which is formed by the downgrowth of the hypothalamus (neurohypophysis)

Describe the pituitary gland

Scalp ringworm Mainly seen in prepubsecent children Range from slight inflammation, scaly patches to alopecia, black dots, grey patches to severe inflammation o Kerion celsi: boggy, inflamed lesions, usually from zoophilic dermatophytes o Favus: presence of cup shaped crusts or scutula o Hair invasion: o Endothrix, spores inside hair shaft (lead to black dots) o Extothrix, spores outside hair shaft o Favic, hyphae only in hair shaft (favus)

Describe tinea capitis

● Fungal infection of the skin ● Aka Ringworm in the limb and torso skin generally ● Caused by Trichophyton (trichophyton rubrum or trichophyton tonsurans) ●Circular, single or multiple erythmatous plaques Invasion of follicle 'Majocci's granuloma' Typical cause: Wide range of dermatophytes-->zoophilic, anthrophilic

Describe tinea corporis

Affects groin area of the skin-->'jock itch' More prevalent in men than women Causes itching, scaling, erythmatous plaques with distinct edges Satellite lesions are sometimes present May extend to buttocks, back and lower abdomen

Describe tinea cruruis

• Trabecular bone is the spongy inner layer and is also known as cancellous bone • It is an open cell porous network. Thin formations of osteoblasts covered in endosteum create an irregular network of spaces. Within these spaces are bone marrow and hematopoietic stem cells that give rise to platelets, red blood cells and white blood cells • Trabecular marrow is composed of a network of rod- and plate-like elements that make the overall organ lighter and allow room for blood vessels and marrow. Trabecular bone accounts for the remaining 20% of total bone mass but has nearly ten times the surface area of compact bone

Describe trabecular bone

IgE mediated Exogenous antigen response time of 15-30 minutes Wheal and flare appearance Histology of basophils and eosiniophils Transferred with an antibody Innocuous antigen is pollen-hay fever Disease states with a similar type of reaction are allergic asthma

Describe type 1 hypersensitvity reaction

IgG and IgM antibody mediated The antigen is on the cell surface Response time is minutes to hours Causes the appearance of lysis and necrosis Histology of antibody and complement Transferred with an antibody Innocuous antigen of pencillin Disease states with a similar recation to type II: Erythroblastosis fetalis Goodpasture's nephritis

Describe type II hypersensitivity

IgG and IgM antibodies against soluble antigen-immune complex deposition Onset of 3-8 hours Causes vasculitis Appearance of erythema (redness of skin), oedema and necrosis Histology of complement and neutrophils Transferred with an antibody The innocuous antigen is mouldy hay farmer's lung Disease states with a similar type reaction-->systemic lupus erythematosus

Describe type III hypersensitvity

translation of RNA-->protein takes place on a ribosome o Ribonucleoprotein complexes (2/3 RNA, 1/3 protein) o 50S (large) and 30S (small) subunits combine to form 70S initiation complex o S=Svedberg units; relative sedimentation rate

Desrcibe protein synthesis in bacteria

Legionella antigen detection test Can be used a s apoint of care test Gives rapid results at the bedside but requires training and quality control which can be a problem

Detection of an anitgen

• Sensitising events • Previous transplant • Pregnancy • Blood transfusion • Prevents hyperacute rejection • Three methods • Complement dependent cytotoxicity test (CDC) • Flow cytometry • HLA Beads

Detection of antibodies

• Anti-dsDNA: • Crithidia luciliae assay (protozoa). • Farr assay. • ELISA. • ENA's: • Immunoblots. • Individual ELISA's. • Combination of antigens. • >100 different antibodies described in SLE.

Detection of dsDNA and ENA's-techniques

o Cushing's syndrome-->excess cortisol o Acromegaly-->excess growth hormone o Somatostatin secreting tumours (somatostatinoma) o Glucagon secreting tumours (glucagonoma)

Diabetes caused by endocrinopathies

≥ 48 mmol/mol = diabetes

Diabetic HbA1c

• Decreases sensation in extremities, poor blood flow, and structural changes within the foot • May result in foot ulcers which is complicated by impaired wound healing • Prevention: • Glycemic control • Annual foot exam (podiatry) • Daily self-foot checks • Diabetic shoes • Non-infected Wounds or Ulcers o "smelly" "weeping" "exudate" are not evidence of infection o Do not send swabs • Mild infection: Wound swabs: Sens. 49% / Spec. 62% • Mod/Severe (Deep) Infection o Debride wound then collect "clean" o Bone or Tissue sample- specialist

Diabetic foot infection

lower UTI

Diagnose this: Pain on urinating Frequency No fever No loin pain

Eggs or worms found in the stool sample Albendazole-->prevents glucose absorption by the worm So then the worm starves and detaches and passes via the rectum

Diagnosis and treatment of ascariasis

Diagnosis: Culture Serology Imaging Treatment: Aspergilloma is resected For allergic aspergillosis, prescribe steroids +/- antifungals For chronic pulmonary aspergillosis and invasive aspergillosis-->prescribe antifungals, itraconazole, voriconazole and amphotecerin B

Diagnosis and treatment of aspergillosis

Diagnosis: microscopy Yeast cells and hyphal segments are described as spaghetti and meatballs Culture may be difficult to obtain and not interpretable Treatment-->topical antifungals e.g. clotrimazole, if this fails then fluconazole or itraconazole

Diagnosis and treatment of pityriasis versicolor

Diagnosis: Clinical diagnosis and empiric therapy Culture with identification and antifungal sensitivity testing where appropriate Treatment: Usually use oral azoles like fluconazole There is highly effective resistance in normally sensitive species e.g. Candida albicans or naturally resistant species like candida krusei which can be a problem IMPORTANT: do NOT use fluconazole or other azoles in pregnant women because this can increase the risk of teratologies (e.g. heart defects), so use topical azoles e.g. clotrimazole

Diagnosis and treatment of superficial candidosis

o Amylase or Lipase o Imaging o Clinical History

Diagnosis of acute pancreatitis

• History, history, history! • Specific IgE (>0.35 KuA/L). • ADVANTAGES - Safe. • DISADVANTAGES - False negatives and false positives. • Skin prick test (>3mm wheal): • ADVANTAGES - Quick and high patient satisfaction. • DISADVANTAGES - False negatives and false positives, antihistamines and a slight risk. • Intra-dermal test. • Graded challenge test - gold standard. • Basophil activation test: • Upon cross-linking of membrane-bound IgE, basophils up-regulate the expression of activation markers (CD63 etc.). • Component resolved diagnostics.

Diagnosis of atopic triad

• Adults 30-60yrs • Diagnosis often difficult: presentation can be very variable o Atypical presentations / non-specific symptoms o Silent disease: Positive serology / villous atrophy but no symptoms o Latent disease: Positive serology but no villous atrophy o Symptomatic patients o Anaemia, chronic diarrhoea, bloating, or chronic fatigue • Non-invasive serologic tests (blood) usually performed before biopsy • The most sensitive tests o IgA antibodies to tissue transglutaminase (TTG) o IgA or IgG antibodies to deamidated gliadin o Anti-endomysial antibodies - highly specific but less sensitive • Tissue biopsy is diagnostic (2nd biopsy after GFD) (gold standard test) o Look down microscope to see the effects of the coeliac on the epithelial o Gluten free diet and take biopsy weeks later to see if improvement

Diagnosis of coeliac disease

Stool sample Acid fast staining Antigen detection by enzyme immunoassay

Diagnosis of cryptosporidosis

upper gastrointestinal endocscope

Diagnosis of gastric cancer

cysts or trophozoites found in stool

Diagnosis of giardiasis

serological tests, X rays, CT, and MRI

Diagnosis of hydatid disease

Viral antigen detection in respiratory samples using PCR

Diagnosis of influenza

Returning traveller + fever =malaria (until proven otherwise) Thick and thin microscopy Serology--detection of antigen in the blood PCR-detection of malarial DNA

Diagnosis of malaria

clinical features + supportive radiology + detection of acid-fast bacilli or culture of M. tuberculosis from clinical specimens (usually sputum). PCR-based tests may be used to detect MTB in clinical specimens. Interferon gamma release assays (IGRA) +/- Tuberculin skin test - Mantoux can be used (do not differentiate active from latent disease)

Diagnosis of mycobacterium tuberculosis

o Often difficult - false negative and false positive results of biochemical tests are not uncommon o Plasmametanephrines o Unstable - collect on ice o Not available in many laboratories o Sensitivity of 99% and specificity of 89% o 24 hour urine fractionated metanephrines o Usual problems of 24 hour collections o Sensitivity of 96-100% and specificity of 94-97% o Remember patient preparation

Diagnosis of phaeochromocytoma

Identification of organism in genital specimens

Diagnosis of trichomoniasis

how does pregnancy alter resistance to infection?

Does not alter resistance, in fact, some infections during pregnancy are more severe and can affect the foetus

a procedure in which repetition of a sequence of operations (tests) yields results successively closer to a desired result (a high diagnostic probability)

Diagnostic iteration

close, long term interaction between two different species

Symbiosis

• Passage of 3 or more loose or watery stools in 24h • Passage of 1 or more bloody stools • Acute diarrhoea = lasts <14d • Accompanying symptoms: fever, Nausea & Vomiting, abdominal cramps/pain, tenesmus • Tenesmus: recurrent inclination to evacuate the bowels caused by a rectum disorder/ other illness-->feeling of fullness in rectum • NO symptom or combination of symptoms sensitive or specific enough to aid in diagnosis of a particular pathogen • Usually mild and self-limiting • But can cause severe disease or complications requiring hospitalisation, esp those with comorbid conditions

Diarrhoea

1. The initial disease e.g. HBV 2. Surgery and hospital admission e.g. S. aureus wound infection 3. Organ receipt e.g. Toxoplasmosis, CMV 4. Opportunistic infection during initial immunosuppression (initial 3/12, e.g. CMV, Aspergillus) 5. Later opportunistic infection (after 3/12, e.g. Zoster, Listeria)

Diary of infections in transplantation

Crohn's disease contains granulomas, UC doesn't

Difference in morphology between UC and Crohn's

o Bacteria are 'prokaryotes' i.e. their DNA exists as a ring-like structure in the cytoplasm o Fungi are 'eukaryotes' i.e. their DNA is separated from the cytoplasm by a nuclear membrane o Size o Bacterial cells are much smaller than fungal cells o Structure o Bacterial cells are uniform simple structures o Fungal cells may have a complex structure and the same organism may have many different forms (hyphae, spores etc) o Cellular processes o Fungal protein and DNA synthesis very similar to human processes

Differences between fungi and bacteria

- An autoimmune process results in clinical hyperthyroidism and diffuse hyperplasia of the follicular epithelium. - Incidence 1% world wide. - Responsible for 80% of cases of hyperthyroidism. - Females much more common than men. - Peak in third and fourth decades. - Symptoms of hyperthyroidism. - Physical findings - Pretibial myxoedema, hair loss, wide-eyed stare or proptosis, tachycardia, hyperactive reflexes. - Thyroid diffusely enlarged. - T3 and T4 elevated. TSH markedly suppressed. - Thyroid autoantibodies, especially thyroid stimulating immunoglobulin. - May develop permanent hyperthyroidism.

Diffuse hyperplasia (Graves' disease)

o Establishes the presence of a micro-organism at a particular site - Cultivable and non-cultivable organisms o Allows the use of appropriate empiric antimicrobial therapy o Does not give any information on: Antimicrobial susceptibility Typing o Is usually the fastest diagnostic method

Direct detection, uses and limitations:

a life cycle that includes a definitive host only, with no intermediate or paratenic hosts involved

Direct life cycle

Fasting blood test o Low blood sugar (less than 2.2 mmol/l) o High insulin (6 microunits/ml or higher) o High levels of C peptide (0.2nmol/l or higher)

How are insulinomas diagnosed?

Poor absoprption Difficult to take Can cause oesophageal/upper GI problems Flu like side effects Osteonecrosis of the jaw Atypical femur fractures

Disadvantages of bisphosophonates

May reduce the time available to do cultures Reduced chance of giving targeted therapy Reduce the chance of getting a diagnosis (the pathogen may give the diagnosis) May reduce the time to do investigations i.e. overtreatment is possible May increase the chance of giving the wrong antibiotic or not enough antibiotic Insufficient time to check allergies

Disadvantages of early antibiotic therapy

o Need several doses o Local reactions common o Adjuvant needed o keeps vaccine at injection site o activates antigen presenting cells o Shorter lasting immunity

Disadvantages of inactivated/killed vaccines

o Potential to revert to virulence o Contraindicated in immunosuppressed patients o Interference by viruses or vaccines and passive antibody o Poor stability o Potential for contamination

Disadvantages of live vaccines

o Imaging o Pancreatic Function test for investigating insufficiency - Direct - Indirect o Miscellaneous: Vitamin D, calcium, FBC, LFTs, glucose, lipids

Disease and management of chronic pancreatitis

1. Barrett's oesophagus 2. Low grade dysplasia 3. High grade dysplasia 4. Adenocarcinoma • Time course variable in everyone, do not know • Similar to bowel cancer, same progression • Barrett's goblet cells and epithelium lining • Low grade: nuclei got bigger, more disorganised • High grade: nuclei atypical, glands disorganised, irregular shapes • Adenocarcinoma: invasive cancers, blue colour • An adenocarcinoma is invasive and is demonstrated as neoplastic cells break through the basement membrane to invade connective tissue

Disease progression of Barrett's oesophagus

o Pancreatitis (caused by gallstones, alcohol) o Pancreatectomy (for cancer, trauma) o Cystic fibrosis o Hemochromatosis

Diseases of exocrine (secondary diabetes) are essentially any condition which damages the pancreatic organ like

• acute pancreatitis • chronic pancreatitis • pancreatic insufficiency • cystic fibrosis • carcinoma of the pancreas

Disorders of the pancreas

• can present with disseminated disease • common sites: lymph nodes, pleura, liver, bone, adrenal, brain • depending on the site can present with pathological fractures, seizures, lumps in necks etc

Distant metastases of lung cancer caused by asbestos

small bulges at weak spots in the colon wall • Blind ending sac like protrusions from the bowel wall in communication with the bowel lumen • 2 types: o True congenital diverticulum: 1-2% of the population o Acquired false pseudo diverticulum: lacking all the cell walls

Diverticula (Large intestine)

inflammation of the diverticula • Not fibre rich and therefore formation of outpouching, therefore overworked • Complicated diverticulitis may be managed with antibiotics and surgery e.g. abscess drainage, resection of the affected bowel • Most common cause of LIF pain in hospital admissions 33% • Antibiotics have no proven efficacy for uncomplicated diverticultis • Inflammatory condition • Pain in left iliac fossa pain: most common cause • Traditionally managed with Abs but symptoms are worse when come into hospital so will recover rapidly, but antibiotics may not always be why they get better i.e. they were going to get better anyway

Diverticulitis

• Protrusions of mucosa and submucosa through the bowel wall • Commonly sigmoid colon • Located between mesenteric and anti-mesenteric taenia coli (longitudinal muscles of the long bowel i.e. band that runs along largew intestine): also between mesenteric t.coli in 50% cases • Less commonly extend in proximal colon e.g. caecum: 15% (Japan, genetic component as more common)

Diverticulosis of the colon

Prevention of transfusion transmitted infection

Donor questionnaire Mandatory testing Hepatitis B - HBsAg Human immunodeficiency virus - anti-HIV 1 and 2 and HIV NAT (nucleic acid testing) Hepatitis C - anti-HCV and HCV NAT Human T-cell lymphotropic virus - anti-HTLV I and II Syphilis - syphilis antibodies. The units found positive are not transfused

oral antibiotic that can be used against MRSA

Doxycyline

• Hepatotoxicity o Intrinsic e.g. paracetamol: every time, predictable Anyone taking this drug is likely to get liver damage o Idiosyncratic: rare, unpredictable, metabolic and immunological • Clinical o Acute liver injury o Hepatocellular o Cholestatic o Mixed • Clinic-pathological diagnosis: role of biopsy o Raised liver enzymes: severe, persistent, diagnostic uncertainty • Exclude other causes o Alcohol, NAFLD o Acute presentation of underlying chronic liver disease o Autoimmune o Biliary o Vascular

Drug induced liver injury classification

meningitis and septicaemia

what does Neisseria meningitidis cause?

Hyperparathyroidism--high PTH and high calcium Bone mets--low PTH, high calcium

hyperparathyroidism vs bone metastases

• Antimetabolites o Azathioprine (AZA) o Mycophenolate mofetil (MMF) • Calcineurin inhibitors o Ciclosporin A (CyA) o Tacrolimus (FK506) • M-TOR inhibitors o Sirolimus • IL-2 receptor mABs o Basiliximab o Daclizumab

Drugs targeting lymphocytes

Main recognised types of breast carcinoma

Ductal - 75% Lobular - 12% Tubular/cribriform - 3% Medullary - 3% Mucoid - 2% Metaplastic - 1% Others - 4%

Delayed haemolytic reaction

Due to post transfusion formation of new immune IgG antibodies against RBC antigens other than ABO Onset is 3-14 days following a transfusion of RBC Clinical features are: fatigue jaundice or fever Lab findings: Drop in Hb Increased indirect bilirubin Increased LDH Direct and indirect antiglobulin test Positive

• Stage A: adenocarcinoma confined to the bowel wall with no lymph node metastasis o Frequency: 10-20%, o 5yr survival: more than 90% o no benefit from chemotherapy just surgery • Stage B: adenocarcinoma invading through the bowel wall with no lymph node metastasis o Frequency: 20-40% o 5yr survival: 60-80% o surgery and chemotherapy usually, treatment after surgery • Stage C: adenocarcinoma with regional lymph node metastasis regardless of depth of invasion o Frequency: 40-50% o 5yr survival: 40-50% • Stage D: distant metastasis present o Frequency: 15-25% o 5yr survival: <5%

Dukes staging: chance of cure: surgeon and oncologist which patients need more treatment

albumin

main carrier of protein bound calcium

Puerperal

During or relating to the period of about six weeks after childbirth during which the mother's reproductive organs return to their original non-pregnant condition. "acute puerperal mastitis"

Organisms which can cause early onset sepsis in neonates

E Coli Group B strep Organisms from maternal genital tract Typical to have multisystem involvement/pneumonia Higher mortality, particularly those infections evident within first 24 hours

o Commonest cause of urinary tract infection (UTI) o Commonest cause of bacteraemia (bacteria in blood)- sources include urinary, biliary and intra-abdominal o Cause of nosocomial infections e.g. line infections, pneumonia, wound infections o Toxigenic strains (e.g. O157) associated with severe diarrhoea and haemolytic uraemic syndrome (HUS)

E.Coli

• Ulcerative colitis • Crohn's disease • Unclassified and indeterminate colitis: 10-15%: overlapping features of UC and CD o Relapse very often

Idiopathic inflammatory bowel disease

plague

what does Yersinia pestis cause?

What is the mode of action of high risk HPV 16 and 18?

Early genes expressed at onset of infection Control viral replication In oncogenic viruses, involved in cell transformation Late genes code capsid proteins High risk HPVs integrate into host genome => upregulation of E6-->E6 binds to and inactivates p53 E7 expression-->binds to RB1 gene product-->this is a tumour suppressor gene which controls G1/S cell cycle checkpoint-->E7 therefore causes dysregulation of cell proliferation p53 mediates apoptosis in response to DNA damage-->accumulation of genetic damage

early onset sepsis in neonates

Early-onset neonatal sepsis (usually within 72 hours) is a major cause of mortality and morbidity in new-born babies. High mortality, particularly in premature and low birth weight babies. Death: 1 in 4 babies who develop it, even when they are given antibiotics. Main pathogens are strep B and E which is passed to the baby during delivery via vertical transmission

o Benign carcinoid tumors of the lung o Small cell tumours of the lung o Islet cell tumours of the pancreas o Medullary carcinoma of the thyroid o Tumours of the thymus gland

Ectopic ACTH secretion is most commonly associated with

Hits fast growing cells like neutrophils

Effect of methotrexate on immune system

kills B cells

Effect of rituximab (immunosuppressant) on immune system

• major risk factor • tobacco smoke = carcinogen • almost a linear dose relationship between the no of cigs smoked daily and the risk of developing lung cancer • pack years: quantifies, 1 pack year: 20 cigs per day for 1 year, 40 cigs per day for 6 months • passive smoking does inc risk for lung cancer • 2/3rd of world smokers reside: China • lung cancer death in China is expected to run into millions by mid 21st century

Effect of smoking on lung cancer

• recognise cells are different • CD4 cells cause effector pathways • 3 ways: • 1. Interact with B cells in lymph to make antibodies (anti orange) • 2. Cytotoxic CD8 cells to kill targets = anti orange • 3. Delayed relay reaction Cd4 cells and will bind and cause influx of macrophages • transplant rejection = combination of antibody production, cytotoxic and DTH response • DTH = delayed hypersensitivity reaction

Effector cell functions

• B cell encounters an antigen a B cell receptor (antibody) which will present to a T helper cell with a MHC complex and then production of cytokines • T helper cells (CD4): produce cytokines that effect B cells and the recruitment of other immune cells • Various T helper 1, 2, 9, 17

Effects of T helper cells on B cells (adpative immunity)

fever fobroblast proliferation endocrine effects--catabolic or anabolic Anorexia T cell activation and B cell proliferation Acute phase proteins Catabolic effects on metabolsim Local effects-->chemotaxis, vasodilatation, cell adhesion proteins

Effects of cytokines

Transfused blood contains citrate that complexes with calcium

Elevated bilirubin Low adjusted calcium Low albumin

Who is screened for breast cancer?

Eligible women from 50-70 years They are invited every 3 years Age is extended in some areas from 47-73 years Mammography is the main tool Provide results within 2 weeks of attendance in more than 90% of cases

1) Centrilobular (centriacinar)--caused by coal dust and smoking 2) Panlobular (panacinar)--more than 80% alpha 1 antitrypsin deficient (rare, autosomal dominant) , severest in lower lobe bases 3) Paraseptal (distal acinar)--upper lobe subpleural bullae adjacent to fibrosis. Pneumothorax if it ruptures

Emphysema classification

Polycystic ovary syndrome

Endocrine disorder Hyperandogenism Menstrual abnormalities Polycystic ovaries 6-10% women (20-30% have polycystic ovaries) Ix: USS, fasting biochemical screen (↓FSH, ↑LH, ↑testosterone, ↑DHEAS ), OGTT Dx: Rotterdam criteria 2/3 of polycystic ovaries, hyperandrogenism (hirsuitism/ biochemical), irregular periods (>35 days) Rx: lifestyle (weight loss), medical (metformin, OCP, clomiphene), surgical (ovarian drilling) Links: infertility, endometrial hyperplasia/ adenocarcinoma

Cytokine mediates secretion of catablic hormones e.g. IL-1 and TNF-alpha Increased ACTH-->cortisol Increased glucagon Increased catecholamines Cytokine mediated inhibition of anabolic hormones: Decreased growth hormone Decreased insulin

Endocrine effects of cytokines

common benign tumour of the breast

Fibroadenoma

Synonyms of fibrocystic change

Fibrocystic disease Fibrous mastopathy Mammary dysplasia Schimmelbusch's disease Chronic cystic mastitis etc

What does the second MDT meeting on the breast involve?

Ensures triple diagnosis For wide local excision with localisation wire Sentinel node biopsy

• Parasite exists in 2 forms: o a cyst stage = infective form o trophozoite stage = form that causes invasive disease • less common nowadays, not common in the UK, if travelled abroad and liver lesion then do serology • infection occurs following ingestion of amoebic cysts: contaminated food or water • associated with venereal transmission through faecal-oral contact • India, Africa, Mexico, parts of central and south America • Amoebiasis is relatively uncommon among short term travelers • Amoebic liver abscesses can occur after travel exposures as short as 4 days • 35% of travelers with amoebic liver abscess had spent less than 6wks in an endemic area

Entamoeba histolytica

Collective term for a number of species of gram negative bacilli found in the normal bowel flora Common species include Eschericihia Coli, Klebsiella pneumoniae and Enterobacter cloacae

Enterobacteriaceae

any of a group of RNA viruses (including those causing polio and hepatitis A) which typically occur in the gastrointestinal tract, sometimes spreading to the central nervous system or other parts of the body. 70 serotypes exist, most were identified in stool samples during polio research o Group includes poliovirus, echoviruses and Coxsackie A and B Epidemiology: - Worldwide distribution - Peak in summer / autumn in UK*** - 75% cases occur in those under 15yrs old - 90% are asymptomatic or have mild febrile illness o Mode of transmission and pathogenesis: - Enteric route: faeco-oral, contaminated food/water. - Replicate in gut, but do NOT cause GI symptoms*** - From gut → lymph nodes → blood - Important clinical syndromes: • Fever-rash syndromes in children, incl. hand foot and mouth • Meningitis (>50% viral meningitis cases are enteroviruses)*** • Can cause severe disseminated disease in neonate

Enteroviruses

Infection Trauma-tissue damage Smoking

Environment triggers for autoimmunity

Ascaris lumbricoides

Example of intestinal nematode

- Children and young adults - 33.9% UK children 12-14yrs with wheeze in 2002 - 1 in 10 UK children diagnosed with asthma - 590,000 teenagers - 9-15% adult onset asthma is occupational: the commonest occupational lung disease o Int: more adults o Extrinsic more common, intrinsic less common

Epidemiology of asthma

• 26/100,000 population Europe • 40-70/100,000 UK

Epidemiology of chronic pancreatitis

41,000 new cases in the UK every year linked to aging: older you are the more likely, average age of presentation = 65 more common in men more common in Western populations

Epidemiology of colorectal cancer

Incidence of 1 per 100 people per year (common!) 20-40% cases require hospital admission Peak age 50-70 years Peak onset midwinter to early spring Acquisition of organisms: Person-to-person or from a person's existing commensals (S.pneumoniae, H.influenzae) From the environment (L. pneumophilia) From animals (C.psittaci)

Epidemiology of community acquired pneumonia

o Common in developed western world o Rare in Africa, Asia, S America: developing here more due to change in diets o Changing prevalence in migrant populations (Therefore environmental factor causing, primarily diet) o Relationship with fibre content of diet o Increases with age: more common with elderly - <40 = rare - 40-60: 10% - >60: 30% - >90: 50% o male = female o less common in vegetarians

Epidemiology of diverticulosis of the colon

o 16th most common cancer in the UK, 6,700 per year = relatively rare o more common with aging (>50% are >75yrs) o male: female = 2:1 (more common in males) o wide geographical variation high rates in Eastern Asia, Andean regions of S America, Eastern Europe

Epidemiology of gastric cancer

Most common cause of cancer death in the UK and worldwide. In the UK around 45 000 new cases are diagnosed each year and > 30 000 deaths/year. M > F, only slight Major public health problem. Age usually between 40 and 70 yrs, rare in younger individuals Cigarette smoking is a major risk factor. Rise in the incidence of Lung Cancer over the last century has closely paralleled the increase in cigarette smoking. Incidence and mortality rates have been decreasing in men since 1990's, due to decrease smoking rates. Overall prognosis is poor, 5 year survival is between 5 - 10%.

Epidemiology of lung cancer

Malignant tumour of glandular epithelial tissue • complex and multifactorial • cigarette smoking: 20% of cases, 2-3x risk, drops with abstinence • family history: 10% cases • also heavy alcohol intake, diet rich in red meats, obesity (especially in adolescence), hereditary 10%, chronic pancreatitis • cigarette smoking and family history are most important 9 x increase in 1st degree relatives

Epidemiology of pancreatic adenocarcinoma

Anthracosis-->accumulation of carbon in the lungs due to repeated exposure to air pollution or inhalation of smoke or coal dust particles Simple (macular) Coal Worker's Pneumoconiosis Nodular CWP Progressive massive fibrosis COPD ('chronic bronchitis & emphysema') if >20yrs underground mining

Examples of Coal Worker's pneumoconiosis

Influenza Measles Mumps Hepatitis A virus

Examples of acute RNA viruses

Adenoma Adenoma of bile ducts Tumours of blood vessels

Examples of benign primary liver tumours

Idiopathic pulmonary fibrosis Many pneumoconioses (dust disease) Sarcoidosis Collagen vascular diseases--associated lung diseases

Examples of chronic interstitial lung diseases

outermost layer of skin Composed of stratified squamous epithelium Produces keratin No blood vessels Constant contact with the external environment

Epidermis

Epiglottitis (supraglottitis): inflammation of structures above the glottis. Almost always caused by bacterial infection. Haemophilus influenzae type b (Hib) was the commonest cause in >90% of paediatric cases but the Hib vaccine has significantly reduced the rate of Hib epiglottis. Still do see Hib cases in adults & rarely in children. Other causative organisms include: Streptococcus pneumoniae & Group A Streptococcus.

Epiglottitis-what is it and what causes it?

• Ultrasound, heat, tissue glue, clips: prevent haemorrhage • Intra-operative ultrasound: see where you are cutting

Equipment required for surgery of a metaststaic carcinoma

Sporadic Creutzfeld-Jakob disease=VERY RARE - 1 in 1 million - Gene mutation -Progressive ataxia (impaired coordination), depression, dementia then death New variant CJD is directly linked to bovine spongiform encephalopathy which is associated with eating infected beef

Examples of human prion diseases:

Hepatocellular carcinoma Cholangiocarcinoma Angiosarcoma

Examples of malignant primary liver tumours

Sarcomas Melanomas Lymphomas

Examples of secondary lung tumours

Infections in neonates

Escherichia coli most common causative organism Usually in conjunction with a neural tube defect, premature rupture of the amniotic membranes, difficult delivery Neonatal sepsis Common childhood infections Respiratory tract Infections UTI Meningitis Rashes associated with systemic diseases

Dull to percuss Reduced air entry, bronchial breathing

Examination findings consistent with bacterial pneumonia i.e. consolidation

• Assessment of: 1. General status of the patient, especially vital signs (calculate a NEWS score) 2. Signs of dehydration 3. Evidence of peritonism (which may suggest an alternative diagnosis)

Examination of someone with gastroenteritis

Schistosoma sp

Example fo a trematode helminth

Taenia sp

Example of a cestode helminth

Rhinosinusitis - Majority viral - Secondary bacterial infection - Caused by upper respiratory flora - Sample in all but severe cases is unhelpful Severe cases: - Pus from operative sinus lavage - FBC, Blood Cultures etc.

Example of a nose infection--explain it

Endometrial hyperplasia Risk factors History Investigations Treatment Prognosis

Excessive endometrial proliferation Benign condition that results from estrogen stimulation to the endometrium without the influence of progestin; frequent cause of bleeding Risk factors: obesity, exogenous oestrogen, PCOS, oestrogen producing tumours, tamoxifen, HNPCC Types: simple non-atypical, simple atypical Complex non-atypical, complex atypical History-Abnormal bleeding-intermenstrual Bleeding, Post Coital Bleeding, Pre-menstrual Bleeding Investigations-ultrasound, hysteroscopy +/- biopsy Treatment-medical: progesterone, surgical Prognosis-endometrial adenocarcinoma, regression

Mantoux o IGRA (Interferon G Releasing Assay) (QuantiFERON-TB, T-Spot TB) o Rely on intact immune system

Exposure testing for pulmonary tuberculosis

• Hepatic o fatty change & granulomas o Primary Sclerosing Cholangitis & bile duct carcinoma: narrowing in the bile duct and predisposes to cancer: 5% of patients with UC and seen in Crohn's as well • Osteo-articular o Polyarthritis o Sacro-ileitis & Ankylosing Spondylitis: joint problems • Muco-cutaneous o oral ulcers o pyoderma gangrenosum (back) & erythema nodosum (painful red nodules on lower limb) • Ocular o Uveitis & retinitis (inflammation of the eye) • Systemic o Amyloidosis o Thrombo-embolic disease: increased clotting, therefore increased risk of DVT, PE and stroke

Extra-intestinal manifestations of IBD

o Pets, smoke, dust mites, viral infections, cold air, exercise, NSAIDS o Often familial o Often associated with eczema and perennial rhinitis in later life (hayfever)

Extrinsic: obvious trigger factors of asthma

Asbestos

Fibrous metal silicates, 5-100mm x diameter 0.25-0.5mm Amphibole - blue asbestos (crocidolite), brown asbestos (amosite) Serpentine - white asbestos (chrysotile) When inhaled some become coated with mucopolysacharides containing iron to form asbestos bodies Asbestos bodies can be seen in tissue sections by light microscopy, brown when unstained or blue if the iron is stained, and quantified - a cheap simple process Asbestos fibres can be quantified in lung extracts by election microscopy - a complex expensive process

Asbestos associated pleural fibrosis

Fibrous plaques on the parietal pleura Diffuse pleural fibrosis

Hep B and C Hep A does not cause chronic hepatitis

major causes of liver disease worldwide

o TSH levels may transiently rise into the hypothyroid range (>10 mU/L) in the recovery phase following a period of illness. o Illness can also reduce the levels of TBG or modify its capacity to bind T3 and T4, hence increasing free thyroid hormone levels. o Due to the poor predictive value of thyroid function tests in hospitalised/ill patients, thyroid function tests should only be requested if thyroid dysfunction is suspected. o reduced conversion of T4 to T3

Factors affecting thyroid function test

o Thyroxine binding globulin o Only the free unbound forms are physiologically active o If the level of TBG changes, this results in a change in the level of the free hormones o Therefore, measurement of total hormone levels can be misleading

Factors affecting thyroid function test interpretation

o Age o Gender o Diet o Pregnancy o Time of month o Time of day o Time of year o Weight o Stimulus These need to be kept in mind when interpreting results

Factors which affect reference ranges

Increases availability of sequestered antigens inside the cells This occurs in Systemic lupus erythamatosus

Failure to clear apoptotic debris results in what? What condition does this occur in?

o Autosomal dominant o <1% all colorectal cancer o 100% lifetime risk of large bowel cancer: classical <100% attenuated FAP o associated with multiple benign adenomatous polyps in the colon o due to mutation in the APC tumour suppressor gene - inheritance of mutated tumour suppressor gene, 100% risk if inherit this gene and will be removed in your 20s before you develop o large bowel cancer develops as have thousands and thousands of adenomas, whole lining of the large bowel covered in polyps and each one has a risk of developing cancer and therefore large risk as have so much

Familial adenomatous polyposis

Clinical features of puerperal endometritis

Fever (38.5oC in first 24 h post delivery or >38.0 for 4 hours, 24 h+ after delivery) uterine tenderness purulent, foul-smelling lochia increased white cell count general malaise, abdominal pain

Redness of the epidermis No damage to the dermis Superficial burn, only affects the epidermis No sensory receptors in epidermis but you feel pain as it is still intact in the dermis

First degree burn

• Simultaneous measurement of Ca and PTH • Consider the adjusted calcium equation - look at the albumin concentration o Could measure ionised calcium on blood gas analyser • Bone profile (adjusted calcium, phosphate, ALP) • Vitamin D • Magnesium • Simultaneous measurement of Ca & PTH • Consider rarer causes & more complex investigations

First line biochemical investigations for hypo/hypercalcaemia

illness caused by a toxin formed in the food prior to consumption S.aureus Bacillus cereus Clostridium perfringens Clostridium botulinum Infant botulism

Food intoxications

-microbial suspension forced through small orifice with a laser light beam -movement of microbe through orifice impacts electric current that flows through orifice -instances of disruption of current are counted -specific antibodies can be used to determine size and internal complexity • See shift with detector and if shift then not matched • Antibodies to class 1 molecules then will see shift • More sensitive

Flow cytometry

o Benign encapsulated tumour with evidence of follicular cell differentiation o Females are affected more than males o Wide age range, usually 5th to 6th decade o Painless neck mass, often present for years o Solitary nodule involving only one lobe o Usually cold nodule on radioactive iodine imaging

Follicular adenoma

Follicular adenoma o 10-20% of all thyroid cancers o 90% present with solitary nodule in thyroid o 10% present with distant metastasis o Minimally invasive < 5% metastasis o Widely invasive >60% metastasis

Follicular neoplasm

o Clonidine suppression test o Useful in patients with suspected pheochromocytoma and borderline changes in catecholamines or Metanephros's o Plasma Chromogranin A o Sensitivity 83%, specificity 96% o MRI or CT of adrenals o MIBG scan, especially to detect extra-adrenal pheochromocytomas or metastases o Genetic counselling and screening for MEN mutations in young patients, or those with a family history

Follow up tests for phaeochromocytoma

Small bowel: mucus plugging - meconium ileus Liver: plugging of bile cannaliculi - cirrhosis Salivary glands: Similar to pancreas: atrophy and fibrosis 95% of males are infertile

How are the small bowel, liver and salivary glands affected in cystic fibrosis?

Campylobacter Salmonella Shigella E coli O157

Four most common bacteria

Why are young infants particularly more vulnerable to infections?

Frequent hand-to-mouth behaviors Still learning appropriate hygiene skills (keeping fingers out of nose, covering coughs, proper hand washing, etc) Some children may not be fully immunized, such as young infants Children have close physical contact/do not practice much social distancing

Diagnsotic tests for haematology

Full blood counts Blood films (or smear) Coagulation screen

• Exocrine: secreted as enzymatically inert, otherwise pancreas would digest itself • Activation requires conversion of trypsinogen to trypsin in the duodenum • Trypsin inhibitors e.g. SPINK1 are present in the acinar and ductal cells • Acinar cells: pyramidal shaped epithelial cells arranged around a central lumen into which enzymes are secreted o Most of pancreas: 85% o Gland-ducts-duodenum o Secrete digestive enzymes: - Trypsin - Lipase - phospholipase - elastase - amylase: marker of pancreatic inflammation which require activation • Endocrine o 1mil clusters of cells: islets of Langerhans o secrete peptide hormones into blood e.g. insulin and glucagon o 1-2% of pancreas

Function of the pancreas

• Liver has massive reserve • Excess of hepatic capacity for normal anabolic and catabolic processes • Hepatic repair and regeneration following damage is a dynamic process

Functional capacity of the liver

• Functioning means whether it is producing a clinical syndrome • Insulinoma is the commonest NET • Produces hypoglycaemia due to hypersecretion of insulin • Patient develops confusion, psychiatric disturbance and possibly coma • Hypoglycaemia can produce permanent cerebral damage so diagnosis is urgent • Most insulinomas are benign but are still resected in case

Functioning pancreatic endocrine neoplasm (PEN)

Describe white blood cells (leukocytes)

Functions for immunity and host defence Types of white blood cell: Granulocytes-->have cytoplasmic granules like neutrophils, eosinophils, basophils Monocytes Lymphocytes

type of nucleic acid (DNA or RNA) presence of an envelope, shape, size

How are viruses classified?

• Cytokines determination in serum. • Detection of antigen specific autoimmune T and B cells. • T-reg detection - measure of therapeutic response. • Personalised medicine: • Genetic profiling to determine individual risk of the disease and to tailor the most appropriate therapy.

Future of diagnostic testing in investigation of autoimmune diseases

• Infectious diarrhoea o Viral gastroenteritis o Bacterial o Parasitic infection o Clostridium difficile infection (CDI) • Helicobacter pylori infection • Liver abscess •Cholangitis/cholecyctitis • Diverticulitis

GI tract infections

Genome wide association study study in which thousands or millions of variable sites tested for association with human diseases sequence the conditions that they have and see if relation to HLA sequencing

GWAS

o Cholesterol, bile salts, bacterial growth and calcification o Slowly form a stone: calculus

Gallstones Aetiology

Gastric cancer: malignant neoplasm developing in the stomach Sites of cancer can occur anywhere from gastro-oesophageal junction to the angular where the stomach becomes the duodenum

Gastric cancer site

Poorly differentiated Scattered growth Cadherin loss or mutation Do not form glandular structures

Gastric cancer: diffuse type

Well or moderately differentiated May undergo intestinal metaplasia and adenoma steps

Gastric cancer: intestinal type when looking down a microscope

o Ischaemia o Shock o Delayed emptying o Duodenal reflux o Impaired regulation of pepsin secretion

Gastritis can be caused by impaired defences like

o Excessive alcohol: erodes the epithelium lining o Drugs: especially NSAIDs e.g. aspirin o Heavy smoking o Corrosive o Radiation o Chemotherapy o Infection

Gastritis can be caused by increased aggression, give examples

• Meconium ileus at birth: 15%: may require surgical resection, associated risk of intestinal failure • Severe hepatobiliary disease: hepatic metabolism of lipids, steroid hormones, drugs and toxins compromised • Pancreatic cysts, exocrine insufficiency: o dec insulin--> diabetes o dec lipase--> lipid malabsorption, steatorrhoea, fat soluble vit deficiency (E K A D) o dec proteases--> protein malnutrition • poor appetite, failure to thrive, low weight

Gastrointestinal disease in CF

• Comes from short arm of chr 6 • Class 1 in one area, class 2 in other and other classes also • Class 1 = 3 types = a, b or c • Class 2 = DR type • HLA molecules = highly polymorphic • Number of alleles: inherit one from one mother and one from father • Variation in gap between: space between 2 alpha helices = polymorphism here • Space allows for many different antigens to fit = great variability

Gene structure for MHC-MLA=chromosome 6

Prescribing broad spectrum antibiotics This destroys normal gut flora so there is less competition and other bacteria can overgrow C.diff is a toxin producer which can cause colitis

How can c.diff develop?

Eradicate H.Pylori

How can the incidence of ulcers be reduced?

By inflammatory cytokines or by helping B cells make autoantibodies

How do T cells cause inflammation?

• More than 100 different diseases that can affect any organ of the body. • Onset in middle or old age. • More common in the elderly and women. • Leads to loss of organ function. • Lifelong chronic condition. • Characteristic exacerbation and remission. • Traditionally divided into organ specific or systemic. • Common for diseases to overlap.

General clinical features of autoimmune diseases

Non-small cell carcinoma, lacks features of squamous cell carcinoma and adenocarcinoma

what does a large cell carcinoma show?

o Mature onset diabetes of the young o Mitochondrial diabetes o Maternal inherited diabetes and deafness

Genetic diabetes

Genetic influences are not sufficient for disease, they only make one susceptible • Polygenic disease. • Cytokine gene cluster IL3, 5, 9, 13. • IL12R and IL4R. • FcERI. • IFNy and TNF.

Genetic influences on the allergic immune response

Susceptibility to type 1 diabetes is inherited, but the mode of inheritance is complex and has not been completely defined. HLA Class II DR4-DQ8 DR3-DQ2 o Exposed / trigger to environmental factors o Autoimmunity

Genetics of type 1 diabetes mellitus

Vast majority of bowel cancers develop along the adenoma-carcinoma sequence Stages Normal epithelium 5q mutation or loss FAP Hyper-proliferative epithelium Early adenoma DNA hypomethylation 12p mutation K RAS Intermediate adenoma 18q loss DCC Late adenoma 17p loss p53 Carcinoma Other alterations Metastasis Each one of the stages there are genomic events that happen within the cell that give rise to progressing further down the pathway Not all happen in this sequence or need to happen at all, but there are multiple genetic hits and with each hit = more consequences and more progression through the stages

Genomic events in colorectal cancer which progress the disease

- Presents with red swollen painful and bleeding gums, and halitosis - Clinical diagnosis. Requires improved oral hygiene

Gingivitis

Corynebacterium diptheriae: Classic cause of diptheriae Rarely seen now in the UK because of immunisation Was a mjor cause of childhood mortality

Give an example of a corynebacterium species

resistant to antibiotics traditionally used to treat them o Meticillin-resistant Staphylococcus aureus (MRSA) o Vancomycin/glycopeptide-resistant enterococci (VRE/GRE) o Extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL) o Carbapenemase-producing Enterobacteriaceae (CPE) o Multi-drug resistant tuburculosis (MDR-TB) o Extremely-drug resistant tuberculosis (XDR-TB) o Others o Enterobacteriaceae resistant to amoxicillin, ciprofloxacin, gentamicin, carbapenems etc. o Pseudomonas resistant to ceftazidime, carbapenems etc.

Give some examples of resistant bacteria

What do NICE say about giving RBC tranfusions to those with chronic anaemia?

Give to patients with thalassaemia major or haemoglobinopathies Give to those with bone marrow failure syndromes People have individualised transfusion plans but the common threshold of Hb is 80-100g/dl

diagnosis based on their nuclear characteristics

what does a small cell carcinoma show?

Pulmonary-renal syndrome, which is a group of acute illnesses involving the kidneys and lungs liver disease DR2

Good Pasture's nephritis

Scarlet fever

Gp A beta-haemolytic Streptococcus 2-4 days post-Streptococcal pharyngitis Fever, headache, sore throat, unwell Flushed face with circumoral pallor Rash may extend to whole body Rough 'sandpaper' skin Desquamation after 5/7, particularly soles and palms School age children White strawberry tongue Dx Throat swab, ASO titres Rx Penicillin 10/7

Classical Vulval intraepithelial neoplasia

Graded VIN 1-3 Related to HPV infection Younger women

• Well differentiated: 10-20% o Nice glands and normal lining shape, tubular structures, mimicking normal lining of the bowel • Moderately well differentiated: 60-80% • Poorly differentiated: 10-20%

Grading of colorectal cancer incidence

Neisseria: Neisseria meningitidis Neissieria gonnorhoae

Gram negative cocci

E.Coli Pseudomonas spp Salmonella spp Shigella spp Klebsiella spp Proteus spp Haemophilus spp

Gram negative rods

Staphylococcus: Staphylococcus aureus Stephylococcus epidermidis

Gram positive Cocci Catalase positive

Streptococcus: Strep pneumoniae Strep pyogenes

Gram positive cocci Catalase negative

gland formation or mucin production

what does an adenocarcinoma show?

Clostridium spp Bacillus spp Corynebacterium spp Listeria spp

Gram positive rods

Bilirubin is produced by RBC breakdown=unconjugated bilirubin Bilirubin is then metabolised in the liver-->conjugated-->excreted in the bile Some bilirubin is reabsorbed from the gut in enterohepatic circulation Bile salts

How is bilirubin metabolised?

anthrax-->serious infectious disease

what does bacillus anthracis cause?

Neonatal infections acquired during passage through the birth canal

Group B Streptococcus Herpes simplex virus (HSV) Gonorrhoea Chlamydia Human immunodeficiency virus* Hepatitis B virus*

Causative organisms of meningitis in neonates

Group B strep E. Coli Listeria monocytogenes

Bacterial pathogens that cause pneumonia in neonates

Group B strep Gram negative bacilli E coli K Pneumonia P roteus spp S aureus

Causative organisms of intra-amniotic infections

Group B streptococcus Escherichia Coli Genital Mycoplasma

human leukocyte antigen

HLA

the process by which the human leucocyte antigens (HLA) present on a person's cells are identified, typically for the purpose of matching a donor tissue or organ to the most compatible recipient • Tissue typing in 1960s used to skin graft and test if body rejected or not before performing transplant • Can type people • Class 1: see antigens for A and B • Class 2: DR • One type from mother, one type from father and therefore will have 4 possible combinations • Therefore 1 in 4 chance that have haploid type with sis or brother • However there are 6000 types in the population = great variation • Serological - cell based • Molecular o Extraction of DNA o Amplification o Detection of sequence polymorphisms (i.e. tissue type) Hybridisation to probes Sequencing

HLA typing

Gardasil

HPV vaccine active against 16, 18, 6, 11

Cervarix

HPV vaccine aganst 16 and 18 for only females (high risk)

• Inborn error of iron metabolism: bronzed diabetes • Relatively common abnormality of HFE gene, the C282Y is the usual severe genotype • Leads to failure of iron absorption regulation, excess iron stored in various organs: liver, pancreas, joints, skin, heart • Patients have high serum levels of transferrin and high transferrin saturation • Large amounts of iron in hepatocytes cause liver injury, then cirrhosis, possible hepatocellular carcinoma • Liver biopsies are stained with Peris' stain for iron = blue, when iron present • Large amounts of iron prompt genetic investigations for haemochromatosis

Haemachromatosis

What does a full blood count include?

Haemoglobin concentration Red cell parameters--Mean cell volume and mean cell haemoglobin White cell count Platelet count

o Gram negative bacillus o Forms part of normal respiratory tract flora o Can cause respiratory tract infections (e.g. pneumonia, infective exacerbations of COPD) o Capsulated types (e.g. type b) associated with meningitis and epiglottitis o Only type b infections prevented by the HIb vaccine

Haemophilus influenzae

Origin of haematopoiesis

Haempoisesis starts at day 27 in the aorta gonad mesonephros region, it expands rapidly at day 35 then disappears at day 40 This "disappearance" correlates with the migration of these hematopoietic stem cells to the foetal liver, which becomes the subsequent site of haemopoiesis

• White plaques on the tongue • seen in HIV patients who have not been treated • caused by Epstein Barr Virus, cause of glandular fever • immunosuppressed can present with white plaques on the tongue

Hairy leukoplakia

stable glycosylated hemoglobin Its percentage concentration indicated cumulative glucose exposure

HbA1c

causes stomach ulcers • H pylori discovered in 1984 • Gram neg spiral shaped bacterium o 2.5-5.0 micrometres long o 4-6 flagellae o lives on the epithelial surface protected by the overlying mucus barrier • damages the epithelium leading to chronic inflammation of the mucosa • more common in antrum of the stomach than the body • results: o glandular atrophy o replacement fibrosis o intestinal metaplasia

Helicobacter pylori

• Bacterial urease hydrolyzes gastric luminal urea to form ammonia that helps neutralise gastric acid and forma protective cloud around the organism = can penetrate the gastric mucus layer • Person to person transmission: faecal/ oral exposure • Humans: major reservoir of infection • H pylori has been isolated from primates in cavity and domestic cats • 10-15% of patients with H pylori develop ulcer disease • cause pain, bleeding, perforation

Helicobacter pylori infection

macroparasite

Helminth

What are pregnanct women screened for?

Hep B HIV Syphilis

Lamvidine and Tenofovir which are nucleoside reverse transcriptase inhibitors

Hep B contains the reverse transcriptase enzyme, which drugs act against this?

• Hepatic causes o Unconjugated - Pre-microsomal - Microsomal - Inherited disorder of conjugation e.g. Gilberts, Crigler-Najjar o Conjugated - Post-microsomal/ impaired excretion - Intrahepatic obstruction - Inherited disorders of excretion e.g. Dubin-Johnson, Rotor

Hepatic causes of hyerbilirubinaemia: jaundice

Jaundice resulting from conditions that affect the liver cells directly, such as viral or toxic hepatitis. • Hepatic: too few functioning liver cells o Liver cells do not work so cannot conjugate bilirubin o Acute diffuse liver cell injury o End stage chronic liver disease o Inborn errors o Mainly conjugated, soluble = patient notices yellow eyes and dark urine

Hepatic jaundice

• Inflammation in the liver: any liver disease that is not neoplastic • Pathology: it is implies inflammation of the liver • Clinically: liver enzymes raised, any cause • Acute hepatitis: acute liver injury caused by something that goes away o Acute liver inflammation can only be directly seen with a liver biopsy (classical pain, swelling, of inflammation doesn't apply o Recent onset, will resolve back to normal as long as the cause does not persist • Chronic hepatitis: chronic liver disease caused by something that doesn't go away o Balance of damage and attempts at repair o Been present for over 6 months o Results in ongoing liver cell injury and progressive structural liver damage of scarring and remodelling • Hepatitis is used for illness with abnormal liver biochemical tests, unless the liver disease is severe, symptoms are mild or non-existent

Hepatitis

a form of viral hepatitis transmitted in food, causing fever and jaundice. Type of Virus: Picorna RNA Route: Faecal-oral Acute jaundice: common Evolution to chronic hepatitis: never Prophylaxis: vaccination, Ig

Hepatitis A

B= blood and body fluids (hep c is the same) Type of virus: hepadna DNA Route: parenteral i.e. via infected blood or bodily fluids Acute jaundice: common Evolution to chronic hepatitis: 10% adults Chronic infection: 350 million Treatment: YES + new ones Prophylaxis: Vaccine, Ig

Hepatitis B

inflammation of the liver caused by the hepatitis C virus (HCV), which is transmitted by exposure to infected blood; this strain is rarely contracted sexually Type of virus: Flavivirus RNA Route: parenteral Acute jaundice: uncommon Evolution to chronic hepatitis: >70% Chronic infection worlwide: 170 million Treatment: YES + new ones Prophylaxis: none

Hepatitis C

Intrinsic e.g. paracetamol: every time, predictable-->anyone taking this drug is likely to get liver damage • Paracetamol toxicity = necrosis of a high proportion of hepatocytes in a predictable, zonal distribution without any inflammation • Hepatocytes around the portal tracts are spared and able to regenerate the liver back to normal if the toxicity is not too severe and patient survives

Hepato-toxic drugs

• Usually arise in cirrhosis • increased incidence worldwide o East: Hep C/ B o West: cirrhosis due to fatty liver disease or alcohol • Composed of malignant liver cells o May contain liver-origin substances e.g. Bile, antitrypsin globules o Secrete AFP (alpha-fetoproteins) which can be detected in the blood and measured

Hepatocellular carcinoma

• Not 2 distinct conditions but a continuum o Recurrent acute can develop chronic pancreatitis o Overlap causative factors o Both genetic and environmental o Experimental protocols can be modified to induce each condition

How are acute and chronic pancreatitis similar?

pairs, chains or groups

How are bacterial cocci arranged?

o Disseminated form of Candidosis o Leukaemia, other haematological malignancy o Candidaemia (Candida in blood) during period of neutropenia (abnormally low concentration of neutrophils in the blood during leukaemia which may or may not be detected) o During neutrophil recovery yeasts lodge in liver and spleen (rarely also kidney) o Abscess formation (bulls eye sign), fever, liver function disturbance o Antifungal therapy may be ineffective as dead fungus continues to trigger inappropriate inflammatory response

Hepatosplenic candidosis

o A, B, C o D = delta, only in people with B o EL waterborne, increasingly recognised in the UK in last few years, zoonosis, pigs o Other viruses cause hepatitis as part of systemic disease: EBV (Epstein Barr virus), CMV (cytomegalovirus), HSV(herpes simplex): usually immunocompromised host

Hepatotrophic viruses

Germline CDH1/E-cadherin mutation Precursor lesions? Surveillance? prophylactic gastrectomy? Increased risk for other cancers Example: Napoleon

Hereditary diffuse type gastric cancer (HDGC)

• Recurrent attacks of severe pancreatitis • Usually begins in childhood • PRSS1 inherited mutations: autosomal dominant • SPINK1 gene: autosomal recessive • PRSS1 inherited mutations (cationic trypsinogen) alter a site on the cationic trypsinogen molecule that is essential for inactivation of trypsin by trypsin itself • Mutations result in trypsin being resistant to cleavage by another trypsin molecule • Small amounts of trypsin activation, results in activation of other digestive enzymes: pancreatitis • SPINK1 gene (serine protease inhibitor Kazal type 1) codes for trypsin inhibitor which helps prevent autodigestion of pancreas by activated trypsin

Hereditary pancreatitis

o HSV-2, 'genital herpes', 'herpes' o Epidemiology: o Exists worldwide, humans are only known reservoir o HSV-2 ~10-20% population o Mode of transmission: o Direct contact with vesicle fluid from lesions o Latency in sensory nerve ganglia*** o Periodic reactivations o Important clinical syndromes: 1. Vesicles / ulcers to skin or mucous membranes - typically genitals / buttocks 2. Meningitis - often follows an outbreak of genital lesions 3. Neonatal herpes - severe disseminated viremia (life-threatening) o Vertical transmission from mother's genital tract at birth

Herpes simplex 2

o Disease names—CMV o Epidemiology-->in the UK % prevalence=~age i.e. prevalence is the same as age e.g. 20% of 20 year olds o Mode of transmission: - Saliva or genital secretions - Donated blood, stem cells or organs • Important clinical symptoms: 1. Infectious mononucleosis (primary infection): (see EBV slide) 2. Congenital CMV infection o In infants born to mothers who have primary infection during pregnancy o Retinitis, deafness, microcephaly, hepatosplenomegaly in the neonate 3. Reactivation in immunosuppressed patients (e.g. transplant patients, advanced HIV) o After primary infection, latency in monocytes / dendritic cells / myeloid progenitors o Reactivation of latent CMV causes retinitis, colitis, pneumonitis

Herpes virus: Cytomegalovirus

o Disease names: - 'Glandular fever', 'infectious mononucleosis', 'EBV' o Epidemiology: - 90-95% in the UK are infected by age 25 - Of these, 50% infected before age 5yrs o Mode of transmission: - Virus is shed in saliva and genital secretions - 'kissing disease' o Important clinical syndromes: o 1. Infectious mononucleosis (primary infection): - tonsillitis, fever, lymphadenopathy, hepatosplenomegaly - atypical lymphocytes on blood film (looked like monocytes - 'mononucleosis')*** - 80-90% of clinical infectious mononucleosis is caused by EBV o 2. Reactivation (from latency in B cells***) - Especially if unwell or immunosuppressed - Associated with malignant B cell lymphoproliferative disorders

Herpes virus: Epstein Barr virus

o Disease names: - Primary (first) infection = 'chicken pox' - Reactivation = 'herpes zoster' or 'shingles'*** o Epidemiology: - In UK, ~95% people have had chicken pox by age 20 - In the tropics this decreases to ~50% o Mode of transmission: o Respiratory droplets from person with chicken pox o Direct contact with vesicle fluid from person with chicken pox or shingles o Latency established in dorsal root ganglion of whole CNS*** o Important clinical syndromes: 1. Chicken pox - febrile (fever) illness with widespread vesicular rash 2. Shingles / herpes zoster - Reactivation causing unilateral vesicles in a dermatomal distribution

Herpes virus: Varicella Zoster virus

Groups, chains or solo

How are bacterial rods arranged?

In the light of the appropriate reference range An understanding of normal physiological regulation is assumed

How are biochemical values interpreted?

vitamin D deficiency

High PTH, low calcium

TSH secreting tumour or thyroid hormone resistance Feedback mechanism fails Pituitary gland overproduction

High TSH and high T4

Unresponsive thyroid gland Primary hypothyroidism

High TSH, low thyroxine

What are the risk factors for cervical squamous cell carcinoma?

High risk HPV is the most important causative factor Multiple sexual partners MAle partner with multiple partners Young age at first intercourse High parity (lots of children) Low socioeconomic gorup Smoking Immunosuppression

Causes of pleural effusion transudates

High vascular hydrostatic pressure could be due to left ventricular failure or renal failure Low oncotic pressure in the capillary (colloid osmotic pressure) may be due to hypoalbuminaemia which can occur because of hepatic cirrhosis or nephrotic syndrome

Biopsy of a fibroadenoma would reveal

High-grade ductal carcinoma in situ (DCIS) with associated comedonecrosis and calcifications. No invasion is seen Left Breast: High Grade DCIS- B5a

How does asbestos cause cancer?

High-level exposure to asbestos dust is an independent risk factor for lung carcinomas of all types About 2000 to 2500 UK lung carcinomas per year, mainly in men, are attributable to asbestos exposure. That is about 5% of the 46,403 cases diagnosed in 2014 Lung carcinoma in specified high exposure occupations is a UK Government Prescribed Occupational Disease that is eligible for Industrial Injuries Disablement Benefit Amphiboles particularly crocidolite are the most oncogenic and persist in the lungs Chrysotile is less oncogenic and is more readily cleared from the lungs Erionite is a fibrous zeolite mineral that has a fiber structure similar to asbestos. It is used as a building material in areas of Cappadocia, Turkey where there is a very high incidence of mesothelioma occurring in young people

enlarged thyroid is composed of hyperplastic follicles lined by hyperactive, tall cuboidal cells. The thyroid also contains lymphoid follicles (sign of autoimmune disease)

Histology of Grave's Disease

Chronic inflammation with germinal centers and Hurthle cells (eosinophilic metaplasia of cells that line follicles)

Histology of Hashimoto Thyroiditis

Malignant glandular tumour Lots of stroma and not many glands

Histology of a pancreatic adenocarcinoma

• A liver biopsy showing these features of steatohepatitis is very likely to be due to alcoholic liver disease - even if the patient has not volunteered the history • Some patients with alcohol injury may just show fatty change: a reversible stage of liver injury that may or may not progress to steatohepatitis

Histology of steatohepatitis

• First sign: bile in the liver parenchyma = jaundice in the skin, patient = yellow • Inc with time: o Portal tract expansion o Oedema o Ductular rection: aproliferation of ductules around the edge of portal tracts o Bile salts and copper can't get out: accumulate in hepatocytes = bile salts in the skin = patient = itchy • Patient with jaundice is first investigated with ultrasound scan (USS) to check for bile duct dilation • Ducts not dilated, then liver biopsy to investigate the cause of jaundice • Characteristic changes in the liver histology that indicate why there is jaundice: distinguish between obstruction to ducts (not always seen on USS), and various patterns of liver cell injury • Features of bile duct obstruction evolve over time • Unrelieved obstruction = severe chronic liver disease and cirrhosis (over months/ years) • over time the portal tracts get larger firstly by swelling (oedema, tissue looks pale), then ductular reaction (inc number of small bile ducts around the periphery of the tracts) and some associated inflammatory cells including neutrophils • Oedema reduces and fibrosis incs • Characteristic appearance: biliary Gestalt

Histopathological features in liver with obstructive jaundice (post-hepatic)

Pneumonia occurring 48 hours or longer after hospital admission and not incubating at the time of hospitalization. Additional causative organisms to CAP, especially if >5days after admission: enterobacteriaceae

Hospital acquired pneumonia

Physical barriers (skin, mucus membrane) Antibacterial secretions (lysosine in tears) Physical removal of microbes (mucus) Presences of normal microflora Immune system Medical procedures often disrupt barriers • Non-specific: innate • Specific: adaptive: humoral and cellular • Congenital or acquired

Host defences

Washing using a surgical scrub

How are a surgeon's hands decontaminated?

Drainage Antibiotics for 4+ weeks, based on the bug

How are brain abscesses treated?

• T cells in the thymus have to develop many receptors to attack different bugs. • They do this by making receptors against everything. • So, some will be auto-immune. • Receptors test it against the body's own antigens. If it matches, it's an auto-reactive T cell and it gets deleted (negative selection). • If it doesn't match, it's positive selection and is released into circulation. • There is a similar process in bone marrow for deletion of auto-reactive B cells.

How do T cells know what's new and what should be tolerated?

o Antibodies produced from B Lymphocytes o Antigen binds non-specifically to variable region of antibody (Ig) molecule. This triggers clonal expansion o 1st wave of IgM production, followed by IgG production o IgG binds tightly to antigen and through simultaneous complement binding facilitates the destruction of the antigen-bearing micro-organism o When infection resolved levels of IgG decline o However, one set of the IgG producing B lymphocytes persist with the ability to recognise that specific antigen = Immunological memory

How do antibodies produce immunity?

Blocka aprticular stage of viral replicaiton

How do antivirals work?

Antibodies against the M protein of Streptococcus also react against the glycoproteins of the heart

How do people with rheumatic fever get heart disease?

1. Know the likely organism E.g. body site-->know where theinfection is and what bacteria usually occupy that region 2. Select an agent with appropriate antimicrobial spectrum 3. Match the pharmacokinetics to the patient

How do you choose the right antimicrobial agent?

Take a clinical history and then perform some blood testing Different autoimmune diseases can have similar symptoms We need to work out which condition the patient has to give them the correct management

How do you specifically work out which autoimmune disease the patient has?

bone marrow transplant to give them new stem cells to make new B and T cells (this is the only real cure)

How do you treat SCID?

review current antibiotics, PPI and start oral metronidazole, vancomycin or fidaxomicin

How do you treat a patient who has developed c.diff from being on broad spectrum antibiotics?

Excruciating retrosternal chest pain due to an intrathoracic oesophageal perforation • these signs require at least an hour to develop after an oesophageal perforation, sometimes only small proportion after an hour • within hrs patients develop: o odynophagia (painful swallowing) o dyspnoea o sepsis o fever o tachypnoea o tachycardia o cyanosis o hypotension on physical examination o pleural effusion may be detected • Cervical perforations: neck pain, dysphagia, dysphonia • Tenderness to palpation of the sternocleidomastoid muscle • Crepitation due to presence of cervical subcutaneous emphysema • Intra-abdominal perforation: epigastric pain that may radiate to the shoulder • Report back pain • Inability to lie supine • An acute (surgical) abdomen • Sepsis may rapidly develop within hrs of presentation • leaking contrast out of oesophagus (left) • gas bubbles leaking from the oesophagus into mediastinum: CT (right)

How does Boerhaave syndrome present?

Long term vitamin D deficiency-->parathyroid hormone cannot absorb adequate calcium-->results in high PTH levels

How does long term vitamin D deficiency affect the parathyroid hormone?

o Many resistance mechanisms are encoded by single genes eg antibiotic-modifying enzymes, altered antibiotic targets o Resistance genes encoded in plasmids o Circular DNA sequences transmitted within and between species o Mainly by conjugation o Horizontal transfer o Enabled by transposons and integrons o DNA sequences designed to be transferred from plasmid to plasmid and/or from plasmid to chromosome o Often contain 'cassettes' with multiple resistance genes o Vertical transfer o Chromosomal or plasmid-borne resistance genes transferred to daughter cells on bacterial cell-division

How does resistance develop and spread?

o Two parts! o Main part migrates from foregut to anterior neck (remnant is foramen caecum at junction ant 2/3 and post 1/3 of tongue ) o Ultimobranchial body forms in branchial arches and fuses with main bit laterally

How does the thyroid get to anterior part of the neck?

Bowel cancer screening helped with dec mortality 2006 commenced, 2010 full national roll out, detects faecal blood participants are asked to put samples of faeces in the little pots sent off to lab and blood detected above certain level, then asked to come in for colonoscopy to identify a source of bleeding therefore picking up cancers at early stages, more treatable and more likely to be picked up then routine presentation when more advanced

How has colorectal cancer mortality decreased?

Respiratory and oral secretions

How is Neisseria meningitidis transmitted?

IV broad spectrum antibiotic like IV ceftriaxone

How is Neisseria meninigtidis treated?

Physical properties-->in living tissue Decontaminated by antisepsis Decontaminated chemically by 2% chlorhexidine in 70% isopropyl alcohol

How is a central venous catheter insertion site decontaminated?

• To stimulate the development of a protective immune response and immunological memory • Immunogenic material o Weakened forms of pathogens o Killed inactivated pathogens o Purified materials (proteins, DNA) o Adjuvants

How is active immunity acquired?

Sensitivity testing: Culture the microorganism in the presence of antimicrobial agent Determine whether MIC is above a predetermined breakpoint level Needs to be high enough to kill the organism Antibiotic needs to be sustained at the site of infection for long enough using practicable dosing regimens i.e. not using higher than necessary (minimum) dose

How is antimicrobial resistance monitored?

• Excretory capacity of the liver and free flow of bile • Measured as: o Total o Unconjugated: pre-hepatic and hepatic o Conjugated: post hepatic (obstructive) and hepatic o Jaundice at serum bilirubin >40-50umol/L Bilirubin Metabolism • Bilirubin is insoluble in water and has to go round with haem • Excreted in the bile and is used in fat absorption • Faeces: brown colour, excreted • Some reabsorbed and given out in the urine

How is bilirubin measured?

relapsing fever

what does borrilea cause?

• Failure of blood lactate to return to normal following trauma resuscitation carries a poor prognosis • Blood lactate (mmol/L): <1, mortality: 18% • Blood lactate 2-4, mortality: 74% • Blood lactate >or equal to 5: 100% • Vicious cycle: o Mitochondrial failure due to hypoxia o Dec oxidative phosphorylation o NADH -> NAD+ o Anaerobic glycolysis continues

How is lactate used a sa prognostic marker in trauma?

• For bone health: o 25-OH Vitamin D < 75 nmol/L is deficient or depleted o 25-OH Vitamin D >75 nmol/L is sufficient o 25-OH Vitamin D > 500 nmol/L suggests toxicity • 29% of 4-18 year olds in the UK have insufficient vitamin D (<50 nmol/L) • Recent resurgence of rickets

How much is enough Vitamin D?

Minimum period to achieve stable concentrations after a change of dose of thyroxine is 2 months and TFTs should not normally be assessed before this Patients stabilised on long term thyroxine therapy should have serum TSH checked annually An annual T4 should be performed in all patients with secondary hypothyroidism on thyroxine therapy

How often should you repeat TFTs in hypothyroid patients?

o Distribution (Where we find them) o Life Cycles (How they survive and breed) o Clinical Manifestations (How they affect the host) o Diagnosis (How we identify them) o Treatment (How we get rid of them) o Control (How we prevent others from getting infected)

How to approach parasites

Stage: how much scarring and remodelling? Grade: how much active injury?

How to assess the severity of chronic hepatitis

• We have tests to detect which autoantibodies are present in the patient's blood. • Use various laboratory techniques to identify these antibodies.

How to detect autoantibodies against self antigens

• Diagnosis: o Urease breath test o Faecal antigen test o Serology (IgG): exposure at bacteria at any point in their life, not just at that specific moment o Culture and sensitivity o Endoscopy and biopsy: usually invasive techniques when on second or third line therapy, as first line treatment has failed

How to diagnose H pylori infection

Terminal stream urine Microscopy Serology Stool microscopy (mor indicative of a diagnosis) -Rectal snip microscopy

How to diagnose schistosomiasis

• 1st part - Put an antigen on a plate. • Separate the patient's serum (antibodies in). • Put antibodies over the plate. • If antibody present for antigen, it should bind. • 2nd part - How do we see if it's bound? • Add an antibody (with a light up label) to the antibody. • 3rd part - put under fluorescent microscope to see if it's lit up. • Different patterns can signify different diseases.

How to identify antinuclear autoantibodies

chest x-ray

How to investigate community acquired pneumonia

o Hand hygiene o Personal protective equipment (PPE) o Aprons o Gloves o Masks o Equipment decontamination o Surgical instruments o Stethoscopes, blood pressure monitors, USS probes etc. o Source and protective isolation o Use of disposable equipment like syringes, needles etc

How to minimise transmission in infection control?

• Name: first give genus name, then species name o Example: Escherichia coli, Escherichia = genus, coli = species o Full bacterial names in italics as originated from latin, most names of bacteria are historial o E.coli is mainly found in the colon therefore coli o Enterococcus: found in the enteric tract and are cocci (round bacteria)

How to name bacteria

• Commonest symptom of Drug Induced liver Injury = jaundice • Recognising drug induced liver injury = combination of clinical history & histopathology • The ratio of liver enzymes: ALT, alk phos is used to classify the type of acute liver injury into hepatic, cholestatic or mixed • Hepatitis and mixed forms have a risk of severe disease and liver failure • Patients should avoid using drugs that have caused injury in the past, antibiotics = common cause • Any drug can cause liver injury • Same drug can cause different injury to different patients • Time of onset variable • Improves on stopping drugs: so usually causes acute but not chronic liver disease but not always

How to recognise drug-induced liver disease

• When taking a history from a patient with gastroenteritis it is important to cover the following elements: 1. Nature of onset (abrupt or gradual) 2. Duration of symptoms 3. Frequency of bowel movements (per 24h) and relative quantity of stool produced 4. Stool characteristics 5. Presence of dysenteric symptoms (blood or mucus in stool, fever, tenesmus, abdominal pain) 6. Symptoms of dehydration 7. Associated symptoms and their frequency/intensity (e.g. nausea, vomiting, abdominal pain/cramps) • Immunocompromised? • Medications • Start with open questions • If started suddenly could be norovirus, lasts 1-3 days, longer could be parasitic causes • Dysentery symptoms: blood or mucus in faeces

How to take a history from someone with gastroenteritis

• Only 3-4% of subjects with abnormal LFTs have liver disease o Alcohol related o Gilbert's syndrome o Obesity o Diabetes o Side effects of medication • Does early diagnosis of liver disease improve prognosis?

How useful are routine LFTs?

Antigens were taken (sera samples) from owmen that had lots of babies or blood transfusions because they are most exposed to a wide variety of antigens, these were tested to see if they would react with leukocytes

How was HLA discovered?

• The diagnosis of RA is clinical. • Combination of symptoms, x-rays and blood tests. • High RhF, CCP and elevated ESR and CRP add to the probability of a definitive diagnosis. • Early treatment can prevent joint damage and significant morbidity.

How would you diagnose rheumatoid arthritis?

Ear swab, determine cause bacteria/fungal etc and sensitvity

How would you investigate acute otits externa?

antibiotic associated diarrhoea

what does clostridium difficle cause?

Molecules found on all nucleated cells in the body that help the immune system to recognize whether or not a cell is foreign to the body. These antigens are inherited from one's parents. Human leukocyte antigens are used to determine the compatibility of kidneys and pancreases for transplantation from one individual to another. The major groups of HLA antigens are HLA-A, HLA-B, and HLA-DR.

Human Leukocyte Antigen (HLA)

toxoplasma gondii

Human infection by this parasite is commonly due to contact with cat faeces?

problem with liver, gallbladder or bones

what does it mean if alkaline phosphatase is high?

relatively aggressive variant of follicular carcinoma o 3% of all differentiated thyroid carcinomas o Median age 53 ( range 24-85 years) o Sex ratio of F:M; 7:3

Hurthle cell carcinoma

the larval stage of the tapeworm Echinococcus that may be found in the lungs or liver of livestock and humans • another cause of liver abscesses • not that common: farmers: sheepdogs and sheep = intermediates • dogs excrete the cysts and ingested by a person and absorbed in the GI tract into the liver • humans = accidental host

Hydatid cyst

meningitis

what does leptospira cause?

listeriosis

what does listeria monocytogenes cause?

• Preformed antibodies: e.g. blood groups, have to have same blood group in kidney transplantation as have preformed antibodies that give us protection but stop transplants • Humans also have antibodies against lower species e.g. tried to transplant pig kidneys: all humans have antibodies against lower forms of species e.g. pigs or apes so therefore rejection common • Xenograft rejection • Anti-Galα1-3Gal • ABO incompatible transplantation • ABO antibodies • HLA incompatible transplantation • Anti-HLA • Damage the graft = 3 mechanisms • Classic: middle one antibody binds and causes complement pathway: inflammatory markers and clotting cascade = black kidney • Leukocytes around bind FC receptors = inc inflammation • Change signalling in endothelial cell • Clinical important, complement activated by product = c4d which binds to the epithelium = diagnostic test • C4d staining: fluorescence: tells whether complement pathway in immune response is activated • Perform pretransplant crossmatch to avoid Hyperacute rejection

Hyperacute rejection

o Polyuria (urinating too much), polydipsia (excessive thirst) o Mood disturbance o Anorexia o Nausea o Fatigue o Constipation

Hypercalcaemia MILD symptoms

o Abdo pain o Vomiting o Coma o Pancreatitis o Dehydration o Cardiac arrhythmias Lethargy, fatigue, depression

Hypercalcaemia SEVERE symptoms

Gonadal failure

Hypergonadotropic hypogonadism (primary failure of gonads) Congenital causes: Turner syndrome (XO), Klinefelter's syndrome (XXY) Acquired causes: Infection, surgery, chemo-radiotherapy, toxins/drugs Hypogonadotropic hypogonadism (hypothalamic/ pituitary failure --> 2ry failure) Sheehan syndrome, pituitary tumours, brain injury Presentation: amenorrhoea/absent menarche; delayed puberty, decreased sex hormone levels +/- Increased LH and FSH levels Ix: Hormonal profiling, karyotyping Rx: Difficult - address cause; HRT

• Rare since kidneys have a large capacity to excrete excess • Usually iatrogenic o Cardiac surgery o Pre-eclampsia • Rule out a drip-arm sample!

Hypermagnassaemia causes

• Common, more common as you get older • 1-5mm in size • often multiple • located in rectum and sigmoid colon • small distal HPs have no malignant potential • no symptoms, no cancer • some large right sided "hyperplastic polyps" (sessile serrated lesions ) may give rise to microsatellite unstable carcinoma (10-15 % all colorectal cancer) o hyperplastic subtype, caecum and transverse colon that are more than 10mm that do cause cancer but very rare

Hyperplastic polyp

• Undesirable, damaging, discomfort-producing and sometimes fatal reactions produced by the normal immune system directed against innocuous antigens in a pre-sensitised (immune) host.

Hypersensitivity

Granulomatous reaction to inhaled organic antigens (e.g., pigeon breeder's lung) aka extrinsic allergic alveolitis Type III hypersensitivity reaction organic dusts farmers' lung - actinomycetes in hay pigeon fanciers' lung - pigeon antigens Peribronchiolar inflammation with poorly formed non-caseating granulomas extends alveolar walls Repeated episodes lead to interstitial fibrosis

Hypersensitivity pneumonitis

a below normal concentration of gamma globulin in the blood associated with a decreased resistance to infection • Antibody problems!! • Congenital - e.g. X-linked agammaglobulinaemia (rare) • Acquired - multiple myeloma, burns • Usually encapsulated bacteria e.g. S. pneumoniae • Parasitic - e.g. Giardia lamblia • Treatment - Immunoglobulin

Hypogammaglobulinemia

• Prevalence in hospitalised patients o Alone on routine estimation 6 - 11% • Associated with: o Hypokalaemia 40% o Hyponatraemia 23% o Hypophosataemia 29% o Hypocalcaemia 25%

Hypomagnasemia

Pleural effusion transudates

Low capillary oncotic (colloid osmotic) pressure and/or high capillary hydrostatic pressure so water moves out of the capillary Intact capillaries retain semipermeability Low protein (<2.5 g/dL) & low lactate dehydrogenase

urinary tract infections

what does proteus cause?

• UC: 5-15 cases per 100,000 pa (UC used to more common than CD, however CD inc) • CD: 5-10 cases per 100,000 pa • Incidence highest in Scandinavia, UK, Northern Europe, USA • Lower in Japan, S Europe, Africa • Peak age incidence 20-40yrs • CD more common in females 1.3:1 • UC equally common in males and females • Incidence of UC is increased in urban areas • Other risk factors: o Cig smoking: UC 0.5 x, CD 2 x o Smoking makes Crohn's disease worse (more severe symptoms) and significantly increases risk of getting it o Smokers have a lower risk of UC o Oral contraceptive: UC 1.4 x, CD 1.6 x o Others: - Childhood infections - Domestic hygiene - Appendicectomy: protective against UC

IBD epidemiology

Induced inadvertently either by: A doctor Medical treatment Diagnostic procedures Drug induced liver injury

Iatrogenic causes of liver pathology

Assymetric self-renewal

Maintain stem cell pool Generation of differentiated progeny

Systemic antifungals: -Griseofulvin, terbinafine, itraconazole -Topical therapy will not be curative but they do have a role in reducing spread

IMPORTANT: what should ALL cases of tinea capitis be treated with?

show keratinisation

what does squamous cell carcinoma show?

• Clinical presentation: can recognise the bug but cannot cause an inflammatory response • Recurrent bacterial infection, especially streptococcus and staphylococcus o Pneumonia, meningitis, arthritis • Poor inflammatory response • Susceptibility to infection decreases with age, develop more and more antibodies as you get older so get better • Rx: prophylactic antibiotics, iv immunoglobulin if severe • MyD88 presents in a similar manner

IRAK 4 deficiency

chronic progressive lung disorder characterized by increasing scarring, which ultimately reduces the capacity of the lungs; etiology unknown Bosselated ("cobblestone") pleural surface due to contraction of interstitial fibrous tissue accentuates lobular architecture aka cryptogenic fibrosing alveolitis 5000 new cases per year in UK, middle aged & elderly 3 & 5 year mortality 43% & 57% (expected 12% & 19%) Sub-pleural, lower lobes affected first & most severely

Idiopathic pulmonary fibrosis

Because in the submucosa, the tumour can access lymphatics and blood vessels and therefore spread around the body

If cells break through from the mucosa into the submucosa, this causes cancer--why?

What do NICE advise about RBC transfusions?

If the patient is BLEEDING-->give RBCs in acute blood loss with haemodynamic instability if the patient had anaemia with SEVERE symptoms-->give RBC transfusion until symptoms resolve but not >100g/l If the patient had acute anaemia with MILD symptoms-->give RBC transfusion of ≤70 g/L for patients without cardiovascular disease ≤80 g/L for patients with cardiovascular disease

Diagnosis of pleural inflammation

If there is no associated pleural effusion: Symptom--pleuritic chest pain, a sharp localised pain exacerbated by breathing Sign--ascultation of a pleural rub during breathing There is frequently a pleural effusion with pleural inflammation, this is excess fluid in the pleural cavity

• Immunopathogenesis: • IgE Ab mediated mast cells and basophil degranulation - release of pre-formed and de novo synthesised inflammatory mediators. • Clinical features: • Fast onset - 15-30 minutes. • Wheal and flare, and can also cause a more systemic response based on severity. • Late phase response: • Eosinophils. • Central role for Th2 T cell.

IgE mediated allergic response

• Antigen is recognised by Th2 and B cell. IL-4 signal to B cell and it proliferates. • IgE is produced. • T helper cell differentiation: • Begins as a naïve CD4+ T cell. • Detects the antigen-presenting cell and pathogen. • Can differentiate into Th1, Th2, Th17 or Treg.

IgE production

(bunch of grapes)

Image of staphylococcus aureus

strawberry tongue

Image of streptococcus pyogenes.

Increased levels of IgE which is specific to the pathogen and is cross reactive Inflammation with eosinophils and mastocytosis Basophil infiltration Presence of CD4+ T cells secreting IL4 and IL13

Immune responses to parasitic disease

What are the contraindications for platelet transfusions?

Immune thrombocytopenic purpura Thrombotic thrombocytopenic purpura Heparin induced thrombocytopenia (decreased platelets) & thrombosis

• disruption of specific defence of an organ/system. Humoral/cellular. • Can often predict infection if know underlying disease • Often organisms of low pathogenicity/opportunistic infections • BUT common things are common

Immunocompromised

• clinical situations where the immune system Is not effective enough to protect the body against infection o Primary: inherent defect within the immune system, usually genetic (usually rare) o Secondary: immune system affected due to external causes

Immunodeficiency

The point of contact between APCs and T cells that stabilizes the interaction to increase the odds of T cell activation • agents in transplantation target the interactions in the immunological synapse • modulated by receptors e.g. TOLL receptors, cytokines etc

Immunological synapse

ability to stimulate and increase immune function • The act of manipulating the immune system using immunomodulatory drugs to achieve a desired immune response • A therapeutic effect of immunomodulation may lead to immunopotentiation, immunosuppression or induction of immunological tolerance • Medicinal products produced using molecular biology techniques including recombinant DNA technology

Immunomodulation

• Immune suppressants • Allergen specific immunotherapy • Anti-IgE monoclonal therapy • Anti-IL-5 monoclonal treatment

Immunomodulators for allergy

Corticosteroids

Immunosuppressive drugs with side effects that includes diabetes, hyperlipidaemia, poor wound healing and osteoporosis?

Liver-cirrhosis Pancreas-diabetes Skin-pigmented Joints-arthritis Heart-cardiomyopathy

In haemachromatosis, iron accumulates in organs of the body--what conditions do these cause?

may cross react to other beta lactam antibiotics e.g. cephalosporins, cefuroxime

In patients with a penicillin allergy, what can happen when given other beta lactams?

What a path report should tell you about malignancy

In situ or invasive Type Grade Size Vacular invasion. Nodal status Relationship to margins Molecular marker status : ER, PR, HER2

Hashimoto's thyroiditis

In this condition, there is destruction of thyroid follicles by an autoimmune process?

Stable Constituents clearly defines Unable to cause infection

Inactivated/killed vaccines advantages

o Haematological malignancy, stem cell and solid organ transplant o Low neutrophil counts o Angioinvasion (tumour masses within blood vessels) of lung tissue o Dissemination in c. 25% of cases to extrapulmonary sites o Halo and air crescent signs on CT o Moderate to poor prognosis, even with aggressive antifungal therapy

Inavasive apergillosis

o 5th most common cancer in the World (951,594 new cases/year) o Wide geographical variation (high rates in Eastern Asia, Andean regions of South America, Eastern Europe) o Steady decline over the past decades

Incidence of gastric adenocarcinoma

o 1.1% of new cancers o 0.32% of cancer deaths o 85% are differentiated thyroid carcinoma o 5-9% are medullary carcinoma o 1-2% are anaplastic carcinoma o 1-3% are malignant lymphoma

Incidence of malignant tumours of the thyroid

o 25-28 cases per 100, 000 population o Caucasian women over 60-->90/100 000 affected o Pathogenesis: - Ageing, tumorigenesis in general - Association with ionizing radiation - MEN 2a (mutations in RET gene)

Incidence of primary hyperparathyroidism

Basophilia

Incraesed numbers of basophils e.g chronic myeloid leukaemia

symmetric self-renewal of haemopoietic stem cells

Increase in stem cell pool No generation of differentiated progeny

What is monocytosis? When does it occur?

Increased circulating monocytes This occurs in tuberculosis

What is eosinophilia and when does it happen?

Increased numbers of eosinophils This occurs in parasitic infection and allergies

What is neutrophilia and when does it happen?

Increased numbers of neutrophils Occurs in inflammation and bacterial infection

What is plasma cytosis? When does it occur?

Increased numbers of plasma cells This occurs in infection and myeloma->blood cancer

Activity of one antimicrobial is unaffected by the addition of another agent

Indifference

PTH acts on the kidneys to increase conversion of vitamin D to its active form-->this increases Ca and PO4 absorption from the gut

Indirect effect of PTH

• Wide range of pathogens: o Viruses (norovirus, rotavirus) o Bacteria (Campylobacter, Salmonella, Shigella, E coli 0157, Vibrio) o Parasites (Cryptospordium, Giardia, foreign travel) o C. difficile infection (CDI) • Laboratory needs guiding with clinical details/ risk factors • Majority of viral and bacterial disease is self limiting • Stool Sample • Why sample: Treatment, Public Health, Avoid transmission • Other investigations: o Parasites- one stool not enough (3 samples improves pick up) o Bloods: FBC, clotting, U&E's, LFT's, CRP o Blood Cultures o Abdominal Imaging: plane film or CT

Infectious diarrhoea

Increased nephrotoxicity with aminoglycosides Loop diuretics

Interaction of glycopeptides e.g. teicoplanin

Epstein-Barr virus (EBV) Teenagers. Often asymptomatic. Characterised by a triad of symptoms: fever, tonsillar pharyngitis, and cervical lymphadenopathy. Complications e.g. splenic rupture Avoid ampicillin (mac-pap rash, not allergy!) Blood for Monospot +/- EBV serology

Infectious mononucleosis/glandular fever/kissing disease

serotonin syndrome-->too much nerve cell activity which can cause: high body temperature, agitation, increased reflexes, tremor, sweating, dilated pupils, and diarrhoea

Interaction of linezolid

puerperal mastitis

Inflammation of the breast in connection with pregnancy, breastfeeding or weaning Infection of mammary duct often associated with lactation (usually S.aureus) in breastfeeding women in the first 6-weeks post-partum or when weaning (breast ducts become blocked with engorged milk, and bacteria enter from cracks in the nipple) but can be non-infectious (accumulation of milk causing an inflammatory response in the breast) 10-30% of breast-feeding women Painful, hot, swelling, red - usually peripheral in 1 breast Systemic features of infection May be engorgement of the breast and axillary lymphadenopathy Infectious mastitis may lead to breast abscess - tender, fluctuant lump with overlying erythema (tend to be systemically well as infection contained) Not possible to distinguish clinically between infectious and non-infectious mastitis Pregnant women who have not yet given birth do not get breast infections - if you think someone in this group has a breast infection they may have inflammatory carcinoma so arrange triple assessment

Endometritis

Inflammation of the endometrium This may be due to: - Pelvic inflammatory disease - Retained gestational tissue - Endometrial tuberculosis - IUCD infection (intrauterine device) - Histology=lymphocytes/plasma cells History-abdominal pain, pyrexia, discharge, dysuria, abnormal vaginal bleeding Investigations-biochemistry/microbiology, ultrasound Treatment-analgesia, antibiotics, remove cause

Types of pleural pathology

Inflammation--pleurisy or pleuritis Fibrosis Neoplasia

eosinophil

Inflammatory cell that is commonly elevated in response to parasitic disease?

C reactive protein <5mg/L Procalcitonin <0.5µg/L

Inflammatory markers are part of the innate immune system, give examples of these and the levels required to indicate infection

1. Bacteria and pathogens enter wound 2. Platelets release clotting factors 3. Mast cells secrete factors that mediate vasodilation to inc blood delivery to the injured area 4. Neutrophils and macrophages recruited to phagocytose pathogens 5. Macrophages secrete cytokines to attract immune cells and proliferate the inflammatory response 6. Inflammatory response continues until wound is healed

Inflammatory response at the site of trauma

• Seasonal, Sporadic vs. Epidemic, highly transmissible • Not necessary to test everyone. Test: o Those who may require treatment o Those at risk of transmitting • Nose/throat swabs- • Immunofluorescence vs. PCR o PCR has sensitivity >90%, specificity 99% o fast, scalable, cost

Influenza

Dusts inhaled: Inert Fibrogenic Allergenic Oncogenic-->can cause lung carcinoma and pleura mesothelioma More than 3 micrometer diameter to reach alveoli Often occupational

Inhaled dusts in pneumoconioses (the dust diseases)

Wilson's disease

Inherited disorder of copper metabolism that results in increased urine copper levels

• Skin (barrier, sebum, normal flora) - e.g. burns • Mucous membranes (tears, urine flow, phagocytes) • Lungs (goblet cells, muco-ciliary escalator. Cystic fibrosis) • Interferons, complement, lysozyme, acute phase proteins • Normal commensal flora in gut - antibiotic treatment alters flora e.g. C. difficile, Candida spp. • (Extremes of age, pregnancy, malnutrition) o neonates more immunosuppressed o elderly: skin = thinner, not eating as properly, kidney and liver not working as efficiently as it used to which usually help with infection Examples: neonate with oral thrush can be given antibiotics for chest infection and then inc risk of thrush Burns patient: strep A and pseudomonas in burns victims, staphylococcus aureus as well as lives on the skin

Innate defences

• Inflammation in target tissues. • Macrophages, dendritic cells, mast cells, neutrophils, complement. • Pattern recognition against broad classes of antigen. • No memory. • No amplification. • Little regulation. • Fast response - hours-days. • Short duration.

Innate immunity

a host that gives food and shelter to immature stages of a parasite I.e. harbours the larval or asexual stages of a parasite Some parasites require two intermediate hosts to complete their lifecycle

Intermediate host

• Anaerobes most likely cause, therefore need to give anaerobic cover everytime! Only grow when oxygen around as cannot survive with oxygen therefore do not get anaerobes reported from histopathology • Localised area of peritonitis with build-up of pus o Subphrenic, subhepatic, paracolic, pelvic etc. • Predisposing factors o Perforation - Peptic ulcer - Perforated appendix - Perforated diverticulum o Mesenteric ischemia/bowel infarction o Pancreatitis/pancreatic necrosis o Penetrating trauma o Postoperative anastomotic leak • May be a late complication o Several months after predisposing factor o Generally require drainage: "If there's pus about...let it out!" o CT/ultrasound guided drainage

Intraperitoneal abscess

o No obvious common allergic trigger factor o Or at least, none that we are aware of as yet o Usually affects middle aged or older people

Intrinsic or non-atopic asthma

Risk factors for breast cancer

Invasive breast carcinoma : estimated that 1/9 women develop Breast Ca in their lifetime. Risk factors : linked to oestrogens. Increased with early menarche, late menopause, obesity in postmenopausal women, Oral Contraceptive Pills and hormonal therapy for menopause, alcohol.

CSF requesting viral PCR specifically

Investigation for encephalitis

• History and exam • Urgent diagnosis and treatment • Blood cultures • Respiratory samples: common problem: sputum etc • Other samples as systems suggest e.g. urine, serology samples: antibody/antigen • Radiology: take imaging • Histopathology: send samples to the labs to get tested to see what antibiotic needs to be used and pathogen causing infection • Hand washing /aseptic technique / protective isolation / HEPA air filtration • Vaccines (avoid live in T-cell deficient) • Prophylactic (preventative) antimicrobials and passive immunoglobulin • Special diet

Investigation of infections

Lumbar puncture to collect CSF 2 sets of blood cultures Blood for bacterial PCR (S.pneumoniae and N. meningitides) FBC, clotting, U&Es, LFTs, glucose, CRP In the immunosupressed: CSF cryptococcal antigen, TB culture/PCR

Investigations and tests for meningitis

WBC, RBC, epithelial cells, bacterial grwoth, sensitivities • Interpretation: o Kass Criteria: threshold for "significant bacteriuria" o Automated analysers: microscopy to predict culture positivity o How the Urine is collected: MSU, CSU, Bag, SPA

Investigations for a UTI

• Bloods: FBC, U&E's, LFT's, Clotting, amylase • Blood Cultures • Imaging: USS or CT • Bile fluid or Pus (if aspirated/drained)

Investigations for cholangitis/cholecystitis

Chest X-ray (can take 6 weeks+ for radiological changes to resolve) Recommended for all moderate-severe CAP based on CURB65 score >2 (BTS guideline 2009) Sputum culture Blood culture Pneumococcal urinary antigen Legionella urinary antigen PCR or serology for: Viral pathogens e.g. influenza (PCR of respiratory samples) Mycoplasma pneumoniae (PCR of respiratory samples preferable, complement fixation: interpret with caution) Chlamydophila sp. (complement fixation test most widely available - on blood)

Investigations for community acquired pneumonia

• Blood cultures fundamental to management (96% positivity) • Three sets of Blood Cultures should be taken at different times during the first 24 hours in all patients with suspected endocarditis • Other investigations: o Echocardiography o Trans-Thoracic Echo TTE (sens. <60%; spec 98%) o Trans-Oesophageal Echo TOE ( sens. and spec. of >94%) o TOE should always be done for suspected PVE o FBC, CRP, U&E's, LFT's o Serology for Bartonella, Chlamydia, Coxiella, Brucella o Valve tissue if valve replaced: M,C and S and PCR

Investigations for endocarditis

SpO2 Chest x-ray Full blood count U&Es Liver function tests C reactive protein Previous sputum culture

Investigations for patients with LRTI with bronchiectasis

3 sputum samples Microscopy & culture for 8 weeks PCR-rapid, costly, lower sensitvity

Investigations for pulmonary tuberculosis

• Calcium and bone profile • U&Es (estimated GFR) • TFTs • FBC • Vitamin D • PTH • Plasma viscosity (+/- myeloma screen) • Coeliac screen • In men: 9am testosterone, SHBG, LH, FSH and LFTs. • In young amenorrhoeic women: LH, FSH, estradiol, prolactin • Loss of height, back pain or kyphosis consider Lateral X-ray T5-L5 spine.

Investigations for secondary causes of osteoporosis

• Three sets of Blood Cultures should be taken at different times during the first 24 hours in all patients with suspected • Lower culture positivity rate than endocarditis • Other investigations: - Imaging: CT, PET, WBC scan- o fluid around graft, fistulae - Tissue/fluid from around graft- for culture or PCR

Investigations for vascular graft infections

Lab assessment Plain x-rays Nuclear medicine bone scan

Investigations of Paget's disease

Blood cultures and epiglottic swabs

Investigations of epiglottitis

• Ultrasound scan to check for dilated ducts in obstruction • Only if no dilated ducts do a liver biopsy to find out the cause of jaundice • Most (non-obstructive) cases are due to acute hepatitis

Investigations of jaundice

• Early: primary and secondary • Latent • Late (tertiary: gummatous, neuro, cardiovascular) • Congenital • Detection by PCR (superseded dark ground microscopy) • Serology: o Screening test including IgM in Primary infection o Treponemal Specific Antibody (eg. TPPH, TPHA) o Non-Treponemal Specific Antibody (eg. VDRL, RPR) Expressed as dilution (1:16; 1:32 etc.)

Investigations of syphilis

• Based on Serology +/- PCR • Serology comprises ANTIGEN and ANTIBODY detection • ANTIGEN- components of the organism • ANTIBODY- body's immune response to organisms (acute IgM and chronic IgG) • PCR detects DNA or RNA from living or dead organisms • Usually presence of DNA/RNA suggests active infection

Investigations of viral hepatitis (A, B and C)

What kind of conditions should you use alternative to transfusions for?

Iron deficiency B12 and folate deficiency Erythropoietin treatment for patients with renal disease (hormone produced by the kidney which promotes the production of RBCs in the bone marrow)

restrictive

Is interstitial lung disease obstructive or restrictive?

• Usually associated with other arterial diseases • colonic injury secondary to an acute, intermittent or chronic reduction in blood flow • may be occlusive (obstruction of the arteries) or non-occlusive (reduction of flow) (NOMI) • usually multifactorial and associated with other vascular diseases: o hypertension o peripheral vascular disease o coronary artery disease o diabetes mellitus o chronic renal failure o IBS o COPD

Ischaemic colitis

in Familial adenomatous polyposis in lynch syndrome: HNPCC

It is rare to have increased susceptibility to colorectal cancer, when would this occur?

• First visible in sclera: white of eye yellows and skin turns yellow • Classified according to where the abnormality is in the metabolism of bilirubin • Visible when bilirubin >40umol/l • Commonest sign of liver disease

Jaundice

Sporadic, hamartomatous (benign) polyp that arises in children (<5 years) • often spherical and pedunculated • 10-30nm • commonest type of polyp in children • typically occur in rectum and distal colon • sporadic polyps have no malignant potential • rare genetic condition: juvenile polyposis associated with increased risk of colorectal (large bowel) and gastric cancer

Juvenile polyp

sepsis and uncontrollable decreased blood pressure (<90/60)

Septic shock

Wheeze Cough Shortness of breath

Key clinical features of asthma

Many tumours ulcerate leading to bleeding ulcers = bleeding due to invading into blood vessels can be occult in the right colon: travelled round the bowel = changed, = no difference seen typically and patients can miss right sided = anaemia, due to chronic blood loss but with no signs of bleedings left side or rectum = bright red and fresh bleeding, passed through the bottom can be stenotic leading to pain stenotic lesion: grows to obstruct the bowel = pain completely obstructs, acutely as surgical emergency weight loss = common altered bowel habit = common, more diarrhoea, constipation, not as regular as usual

Key clinical features of colorectal cancer

o difficulty swallowing (dysphagia) - polypoidal tumour: tumour that bulges and projects from the wall of the stomach into the lumen = difficult swallowing o weight loss o indigestion o feeling full after eating small amounts o vomiting o bleeding/ melaena: if ulcerated cancer - fresh bleeding from the top: haematemesis: vomiting blood - bottom: melaena: blood in the faeces

Key clinical features of gastric cancer

• History key points: o Rapidity of onset of sore throat o Difficulty breathing/speaking o Ability to eat/drink/swallow o Associated neck pain/swellings o Symptoms of systemic infection e.g. fever, chills, rigors, general malaise o Travel history

Key things to ask in taking the history of a sore throat

BENIGN SMOOTH MUSCLE TUMOUR OF UTERUS

LEIOMYOMA

• Serum alkaline phosphatase is elevated in 67 to 90 percent of cases and serum bilirubin and aspartate aminotransferase concentrations are elevated in about one half of cases

Lab investigations of a liver abscess

• Dec aerobic metabolism • Inc anaerobic metabolism • Pyruvate does not undergo oxidative phosphorylation via the TCA cycle but is reduced to lactate • Anaerobic metabolism can only continue until lactate becomes toxic, H+ inhibits enzymes • Inc lactate = tissue hypoxia

Lactate production in hypoxia

Causes of pleural effusion exudates

Leaky capillaries due to inflammation with/without infection Neoplasms either primary or secondary

One of the atypical organisms that cause pneumonia Colonises water piping systems Outbreaks associated with showers, air conditioning units, humidifiers High fevers, rigors, cough: dry initially becoming productive, dyspnoea, vomiting, diarrhoea, confusion Bloods: deranged LFTs, SIADH (low sodium)

Legionella pneumophilia

Endocrine tumours MALT lymphomas (mucosa associated lymphoid tissue) Stromal tumours (GIST: gastrointestinal stromal tumours)

Less frequent gastric cancers

high

Level of ALP in Paget's disease?

inflammatory dermatosis commonly associated with vulval carcinoma

Lichen sclerosus

Ingestion of infective eggs from soil contaminated with human faeces, uncooked produce contaminated with soil containing infective eggs • Infective eggs are swallowed-->larvae hatch and invade intestinal mucosa-->carried to lungs • Larvae mature in the lungs and ascend up the bronchial tree to the throat and are swallowed-->they reach the SI and develop into adult worms

Life cycle of ascariasis

The domestic dog may harbour Echinococcus sp-->dog defaecates on pasture-->sheep feed from contaminated pasture-->dogs are infected through eating infected livestock Human infection occurs by hand to mouth transfer of viable tapeworm eggs from dog faeces

Life cycle of hydatid disease

Anopheles act as a vector i.e. involved in transmission of disease Mosquito injects parasite when it bites the human-->parasite enters the blood and enters the liver-->male/female gametocytes form-->early mosquito stages-->late mosquito stages

Life cycle of malaria

Human urinates or defaecates in the water-->releases eggs-->infects snails-->release parasites-->parasites penetrate the skin when the human goes swimming-->worms released from the snail pair with the liver-->eggs move into the intestines

Life cycle of schistosomiasis

Cryptosporidium lives in the intestine of infected humans or animals An infected person or animal sheds crypto parasites in the stool You can become infected by accidentally swallowing the parasite which may be found in the soil, food, water or surfaces that have been contaminated with the faeces from infected humans or animals

Lifecycle of cryptosporidium

The parasite passes from an infected person to an uninfected person during sex. In women, the most commonly infected part of the body is the lower genital tract (vulva, vagina, cervix, or urethra). In men, the most commonly infected body part is the inside of the penis (urethra). During sex, the parasite usually spreads from a penis to a vagina, or from a vagina to a penis.

Lifecycle of trichomoniasis

what does centor criteria indicate?

Likelihood of a sore throat being due to bacterial infection

- Antibiotics will not treat non-infectious diseases - Antibiotics will not treat contaminated samples - Antibiotics may only be the supporting factor in some infections that require surgical intervention - All antibiotics damage your microbiome i.e. remove normal flora

Limitations of antibiotics

o Gram positive bacillus o Rare but significant cause of sepsis and meningitis in pregnancy, neonates and immunosuppressed patients o Opportunistic pathogens that target immunocompromised o Able to grow at low temperatures o Zoonosis (transmitted from animals) o Associated with consuming cheese made from unpasteurised milk and other foodstuffs Causes listeriosis

Listeria monocytogenes

Condition that may be pyogenic, amebic, or fungal; occur more often as complications of biliary tract disease, surgery , or trauma Caused by: • Ascending biliary tract infection (Coliforms, Streptococci, anaerobes) • Portal vein after peritonitis or colonic perforation (Coliforms, Streptococcus, anaerobes) • Haematogenous e.g. endocarditis (Staphylococcus aureus) • Entamoeba histolytica Protozoal infections and viral hepatitis Increased risk of colonic malignancy

Liver abscess causes

• Pyogenic (bacterial), Hydatid or Amoebic o History to guide aetiology • Pus (if safe to drain) • Stool for OCP • Blood Cultures • FBC, U&E's, LFT's, CRP • Hydatid serology • Imaging: USS/CT

Liver abscess investigations

• When knowledge of liver pathology is necessary to decide on clinical management: diagnosis, treatment and follow-up o Consider risks and benefits of biopsy • Information on: o Stage of disease: query cirrhosis o Cause of disease o Current activity o Response to treatment, if previous biopsies • The benefits of a definite diagnosis (rather than presumed from non-invasive investigations) is balanced against the risks of haemorrhage and puncture of other organs • liver biopsy is performed under ultrasound guidance, and risk of medical liver biopsy is very low • There is a slightly higher risk with targeted liver biopsy taken to diagnose a tumour in the liver

Liver biopsy in chronic liver disease

• Liver biopsy has collagen stained red • Steatohepatitis the collagen surrounds liver cells like chicken wire, incs as portal tract fibrosis • Cirrhosis from alcoholic liver disease is characteristically very fibrotic with small nodules of hepatocytes

Liver biopsy with fibrosis in portal tracts

• Carbohydrates o Glycogen storage and synthesis o Glycolysis and gluconeogenesis • Proteins o Synthesis and catabolism o Clotting factors, amino acid metabolism and urea synthesis • Lipids o Lipoprotein and cholesterol synthesis o Fatty acid metabolism o Bile acid synthesis • Excretion and detoxification o Bile acid and bilirubin excretion o Drug detoxification and excretion o Steroid hormone inactivation and excretion • Miscellaneous o Iron storage o Vit A, D, E and B12 storage and metabolism

Liver function for: Carbohydrates Proteins Lipids Excretion and detoxification Miscellaneous (others)

tests for the presence of enzymes and bilirubin in blood to test for liver injury • Blood tests: biochemistry • Liver enzymes o Leak from hepatocytes: ALT, AST - Mild increase over long time: chronic liver disease - Very high levels: severe acute liver disease o Leak from bile ducts: Alk phos - Therefore high in obstructive jaundice and chronic biliary disease • Bilirubin: usually conjugated, dark urine • Albumin: low in chronic liver disease, long half life • Clotting factors: low in acute liver disease and liver failure, short half life

Liver function tests consists of

• Carbohydrates Glycogen storage & synthesis Glucose • Glycolysis & gluconeogenesis • Proteins Synthesis & catabolism-->Albumin • Clotting factors, Amino acid metabolism-->Urea & urea synthesis • Prothrombin • Lipids Lipoprotein & cholesterol synthesis Cholesterol • Fatty acid metabolism Triglycerides • Bile acid synthesis Bile acids • Excretion & Bile acid & bilirubin excretion Bilirubin detoxification Drug detoxification & excretion Drugs • Steroid hormones • Miscellaneous Iron storage-->Ferritin • Vitamin K -->Prothrombin Time Most effective: albumin, urea and prothrombin

Liver function tests for liver's ability to metabolise carbohydrates, proteins, lipids, others and its ability to excrete and detoxify

• damage to cells in the liver so that enzymes leak from cells (this is a 'damage' test rather than a 'function' test) • Relative increase of Alanine aminotransferase (ALT) and/or Aspartate aminotransferase (AST) v. Alkaline phosphatase indicates whether injury is mainly to hepatocytes, bile duct cells or both • Bilirubin, albumin, clotting factors these are liver function tests: abnormalities because inadequate function of hepatocytes • Raised conjugated bilirubin without extrahepatic duct obstruction indicates disease of hepatocytes or intrahepatic bile ducts • Clotting factors and albumin are proteins manufactured by hepatocytes - so levels fall when insufficient liver synthetic function • Albumin has a long half-life, levels are low in chronic liver insufficiency (and other causes = insufficient intake due to poor diet or malabsorption, or increased urinary excretion due to leaky glomeruli = nephrotic syndrome). • Clotting factors so blood takes longer to clot measured by prothrombin time (PT) and INR (international normalised ratio: ratio of patient's clotting time to normal control). The factors have a short half-life so PT is prolonged after just a few days of severe liver injury. Poor clotting is also seen in patients with obstructive jaundice who can't absorb fat soluble vitamins this is corrected by vitamin K.

Liver function tests indicate

Affects a large part or the entirety of a lobe 90% of the time due to S.pneumoniae

Lobar pneumonia

• central tumours arising in proximal airways can ulcerate and bleed: haemoptysis • tumour obstructing airways with distal collapse or consolidation: breathlessness or features of pneumonia • tumour infiltrating into adjacent structures e.g. o pleura: pleural effusion presenting as breathlessness o chest wall/ribs: pain o recurrent laryngeal nerve: hoarseness o Horner's syndrome: sympathetic chain o oesophagus: dysphagia

Local effects of lung cancer

- Tumour or foreign body -Distal alveolar collapse (total) or over expansion (valvular obstruction) - Distal retention pneumonitis (endogenous lipid pneumonia) and bronchopneumonia -Distal bronchiectasis (bronchial dilatation)

Localised causes of obstructive pulmonary disease

Ulcerated cervical carcinoma

Looking at the picture of an ulcerated cervical carcinoma you can work out what the clinical presentation may be: such a lesion will commonly bleed, or cause a discharge. If the tumour presents late, there could be signs and symptoms due to local spread, for example into the bladder or affecting the ureters causing hydronephrosis (swelling of kidney due to build up of urine) and urinary symptoms.

hypoparathyroidism

Low PTH, low calcium and high phosphate

secondary hypothyroidism

Low TSH; low free T4

Renal patient, likely due to low activated vitamin D

Low calcium High phosphate, ALP, creatinine and urea

Trachea Bronchi Bronchioles Lungs

Lower respiratory tract consists of

Bronchiectasis: acquired disorder of the major bronchi and bronchioles that is characterised by permanent abnormal dilatation and destruction of bronchial walls Chronic cough, mucopurulent sputum production and recurrent infections (e.g. S.aureus, H.influenzea, Pseudomonas aeruginosa, viruses).

Lower respiratory tract infection with bronchiectasis

CF: an inherited disease caused by a genetic mutation on chromosome 7 resulting in abnormal production and function of the cystic fibrosis transmembrane conductance regulator (CFTR). The defective CFTR chloride channel function results in viscous secretions. Colonising organisms & resistance change over time: Staphylococcus aureus in childhood Pseudomonas aeruginosa in childhood/early adolescence (attempts will be made to eradicate) Burkholderia cepacia complex: very resistant & transmissible Non tuberculous mycobacteria & Fungi Acute exacerbations: Use most recent sputum culture results to guide treatment Prolonged antibiotic courses (3-4 weeks not uncommon) General measures: postural drainage, deep breathing, coughing, exercise, aerosolised DNAase etc+ Influenza and Pneumococcal vaccinations. Lung transplant.

Lower respiratory tract infections with cystic fibrosis

• Recombinant HLA proteins and stuck on Bs • Take serum and add 1000 different HLA and can measure them and find out with antibodies they have • Very fast • Very sensitive

Luminex screening

Broadly classified as small cell carcinoma and non-small carcinoma

Lung carcinomas

Natural killer cells

Lymphocytes that are part of the innate immune system Large granular lymphocytes Recognise non-self cells and viruses

o 1-2% all colorectal cancer o autosomal dominant o 50-70% lifetime risk of large bowel cancer o inc risk of endometrial (uterine), ovarian, gastric, small bowel, urinary tract and biliary tract cancer o due to mutations in DNA mismatch repair genes o two thirds distal to splenic flexure: most common where they occur

Lynch Syndrome (HNPCC)

• Severe acute hepatitis, whole confluent areas of hepatocytes have died in some or all of the liver • Affects a high proportion of the liver, the patient will have severe liver failure with risk of death

Severe acute hepatitis

Other pathogens (not viruses or bacteria) which cause pneumonia in children over 5 years

M.pneumoniae C.pneumoniae

Classification of anaemia: macrocytic

MCV >95 fl Megaloblastic: Vitamin B12 or folate deficiency Non-megaloblastic: alcohol, liver disease, myelodysplasia, aplastic anaemia etc

the requirement that immune cells share the same MHC or "self" antigens in order to interact and immunologically respond together • a given T cell can interact with both the self MHC molecule and the foreign peptide that is bound to It, but will recognise and respond to the antigen, only when it is bound to a particular MHC molecule. • Foreign peptides (antigens) are brought to the surface of the cell and presented to T cells by proteins called MHC

MHC restriction

MRSA (methicillin resistant staphylococcus aureus)

what does staphylococcus aureus cause?

• Cow's milk. • Egg. • Legumes - peanut, soybean, tree nuts. • Fish. • Crustaceans/molluscs. • Cereal grains.

Major food allergens

• Polyploidal (left) gives trouble swallowing • structuring: restricts lumen--> reducing oesophagus -->difficulty swallowing • ulcerated: ulcers

Macroscopic appearance of oesophageal cancer

o Ill defined, infiltrative o Some encapsulated o May be cystic o Granular

Macroscopic appearance of papillary carcinoma

• Exophytic or polypodal • Some can be flat or excavated • Plastic: ulceration involve all the stomach • Polypodal: many polyps • Ulcerated: have to take biopsies if see an ulcer as could ulcerated cancer

Macroscopic subtypes of gastric adenocarcinoma

o Proximal extension of the squamo-columnar junction o Squamous mucosa replaced by columnar mucosa = glandular metaplasia o Replicate the stomach or the intestines

Macroscopy and histology of Barrett's oesophagus

Pleural microanatomy

Made up of mesothelium and connective tissue

• predominantly kidneys o Mg is freely filtered at the glomerulus then reabsorbed at the proximal tubule and the thick ascending loop o The distal convoluted tubule provides fine tuning of magnesium levels • PTH release is stimulated by dec in magnesium and inhibited by an inc in magnesium (but calcium is more potent stimulus) • However PTH release is magnesium dependent, so severe hypomagnesium will inhibit PTH release and cause hypocalcaemia

Magnesium homeostasis

Hyperacidity-->give PPi therapy to reduce the amount of acid H.Pylori infection (main one) Duodeno-gastric reflux Drugs: NSAIDs Smoking

Main aetiological factors of peptic ulcer disease

classes: o Substance that are nearly identical to the body's own key signalling proteins o Monoclonal antibodies o Fusion proteins

Main classes of immunomodulators

Naturally occurring fungus that is present on all human skin, but is responsible for dandruff when it grows out of control. Genus of yeasts o E.g. M. sympodialis, M. restricta and M globosa o Part of normal skin flora in all humans from shortly after birth o Most frequent on head and trunk o Causes of disease: Pityriasis versicolor o Role in seborrhoeic dermatitis and atopic eczema

Malassezia

Malignant (necrotising) external otitis occurs when external otitis spreads to the skull base (soft tissue, cartilage, and bone of the temporal region and skull). Can be life threatening Most commonly develops in elderly diabetic or other immunocompromised patients

Malignant (necrotising) external otitis

High Grade Ductal Carcinoma in Situ (DCIS)

Malignant clonal proliferation of cells within breast parenchymal structures. No evidence of invasion. A precursor of invasive carcinoma. Most commonly identified as microcalcifications on screening. Pure DCIS cannot produce a metastasis Has the potential to progress to invasion if left.

Tumours within the lung that possess potentially lethal abnormal characteristics that enables them to invade and metastasize/spread to other tissues

Malignant lung disease

o Carcinoma o Carcinoid o Leiomyosarcoma o GIST--gastrointestinal stromal tumour o Lymphoma o Metastatic tumour

Malignant neoplastic polyps

Negative nitrogen balance Muscle wasting Widespread cellular dysfunction Associated with: Infection Poor wound healing Changes in drug metabolism Prolonged hospitalisation Increased mortality Overall malnutrition in hospitalised patients is approxiamtely 50% Caution--refeeding syndrome

Malnutrition consequences

Monitor disease activity using bisphosphonates, there should be decreased osteoclastic function due to high bone turnover Bone markers: alkaline phosphate or P1NP to monitor disease activity Give IV bisphosphonates which keeps the disease quiet for years

Management of Paget's disease

- Oral analgesics (paracetamol, ibuprofen) - Most acute sore throats do not require antibiotics . Consider antibiotics in non severe acute tonsillar pharyngitis if symptoms present for 1 week and getting worse. (Give antibiotics in severe acute tonsillar pharyngitis, quinsy or epiglottitis).

Management of acute sore throat

Acute epiglottitis and associated upper airway obstruction has significant morbidity and mortality and may cause respiratory arrest and death within 24 hours. Securing the airway & oxygenation is a priority! IV antibiotics (usually 3rd generation cephalosporin--broad spectrum) Analgesia Hib epiglottitis - Inform public health Attempting to examine the throat may result in total airway obstruction (only do when anaesthetic support present)

Management of epiglottitis

o Diet (if mild) o Limited oral option of metformin or gilbenclamide o Majority require insulin but only during pregnancy

Management of gestational diabetes

• Treat the known infection - empirical, need specimens from likely site of infection to guide therapy • E.g. remove catheters • Reverse defect if possible/stop immunosuppression • Prevention most important

Management of infection in organ transplantation

Small % of patients are diagnosed with early stage (disease limited to lung or extension into local nodes), are offered Surgery or radical radiotherapy. The majority present with advanced disease - Until recently the options were limited to Chemotherapy or Palliative Radiotherapy.

Management of lung cancer

o Avoidance of all oral intake o Nutritional support, typically parenteral o Antibiotics o Intravenous proton pump inhibitor o Drainage of fluid collections/debridement of infected and necrotic tissue, if present and surgical consultation should be obtained for all patients

Management of oesophageal rupture

As with any unwell or septic patient, do ABC Then prompt empirical antibiotic therapy

Management of pneumonia

Antibiotics are recommended for exacerbations with acute deterioration with worsening symptoms Non-antimicrobial management: - Effective clearance of respiratory secretions e.g. physiotherapy, postural drainage - Nutritional support - Identification and treatment of underlying cause - Annual influenza vaccination

Management of someone with LRTI with bronchiectasis

What does the third MDT meeting about the breast involve?

Margins clear, but lymph nodes are usually involved by this point First axillary clearance Chemotherapy and radiotherapy

Pleural effusion exudates

Mass of cells & fluid has seeped out of blood vessels or an organ especially in inflammation. Effusion is usually unilateral Pathological capillaries lose semipermeability-->'leaky vessels' Normal capillary oncotic pressure and normal vascular hydrostatic pressure High protein (>2.9 g/dL) & high lactate dehydrogenase

Platelet transfusion in the treatment of bleeding

Massive haemorrhage maintain platelet count >50 x 10^9/L Critical site bleeding (CNS) maintain platelet count >100x 10^9/L Other clinical significant bleeding maintain platelet count >30x 10^9/L

through epithelium, mucosa, submucosa and into muscularis propria

T2 tumour stage

through the muscularis propria, basal layer, and getting into the pericolic/perirectal tissue

T3 tumour stage

Infection of the mastoid bone and air cells The most common complication of Acute Otitis Media - incidence significantly reduced with the use of antibiotics for OM Mastoiditis and other severe complications of AOM are very rare in adults Occurs in <1 in 1000 children with untreated AOM Clinical features: fever, posterior ear pain and/or local erythema over the mastoid bone, oedema of the pinna, or a posteriorly and downward displaced auricle CT scan always required Treatment: Analgesia, IV antibiotics +/- mastoidectomy

Mastoiditis

Classification of anaemia: normocytic normochromic

Mean Cell Volume 80-95 fl & MCH ≥ 27 pg Many haemolytic anaemias Anaemia of chronic disease (some cases) After acute blood loss Renal disease Mixed deficiencies Bone marrow failure (e.g. post-chemotherapy, infitration by carcinoma etc)

Classification of anaemia: microcytic hypochromic

Mean Cell Volume < 80 fl & MCH < 27 pg Iron deficiency Thalassaemia Anaemia of chronic disease (some) Lead poisonng Sideroblastic anaemia (some cases)

Why not screen below 25 years?

No supportive evidence base High HPV carriage rate, including high risk types but 70-80% will be cleared Reactive changes produce confusing cytology Unnecessary Large Loop Excision Transformation Zone procedures can have obstetric consequences

• Aim is to divert the immune system or alter it. • Ratio of Th1 and Th2 cytokines are increased. • Production of IL-10 by monocytes, macrophages, B cells and T cells is increased. • Reduced number of mast cells and their ability to release mediators. • Recruitment of eosinophils and neutrophils to sites of allergen exposure is reduced.

Mechanism of immunotherapy in allergen-specific immunotherapy

o Drug inactivation or modification via enzymes-->staph aureus—pencillinase and E.Coli produces carbapenemase o Alteration of target or binding site like methicillin resistant staphylococcus aureus which alters the penicillin binding site o Reduce drug accumulation via an efflux pump which is the main mechanism of resistance to tetracyclines i.e. antibiotic enters but is pumped out straight away so has no effect o Alteration outer membrane permeability-->porin loss in Pseudomonas aeruginosa which means antibiotic cannot get into the bacterial cell o Alter the metabolic pathway-->resistance to folate synthesis antagonists in mutants which can use exogenous thymine or thymidine for DNA synthesis oMethicillin=flucloxacillin; cannot bind to binding site

Mechanisms of drug resistance

• Immunisation • Replacement therapy • Immune stimulants • Immune suppressants • Anti-inflammatory agents • Allergen immunotherapy (desentisation) • Adoptive immunotherapy

Mechanisms of immunomodulation

1. Absent target--not giving the right antibiotic for the right pathogen e.g. giving it for a fungal infection 2. Decreased permeability--antibiotic doesn't get into cell e.g. vancomycin in gram negative bacteria 3. Target modification--antibiotic can't engage with the target so can't kill the cell e.g. MRSA which alter the penicillin binding site 4. Enzyme degradation e.g. bacteria produce beta lactamases 5. Drug efflux-->bacterial cell wall has developed a system to actively export the antimicrobial agent

Mechanisms of resistance of bacteria to antibiotics

injury to SI due to lack of blood supply • Arterial embolism: 40-50% especially cardiac e.g. MI, AF< endocarditis • Arterial thrombosis: 25-30% especially SMA origin • Non-occlusive mesenteric ischaemia: 20% o Low cardiac output with mesenteric vasoconstriction = low flor state o E.g. MI, CCF (congestive cardiac failure), major surgery and trauma

Mesenteric ischaemia

involves peritoneal lining of the bowel = spread through the peritoneum

T4 tumour stage

megaloblastic anaemia

Megaloblastic anemia is an anemia (of macrocytic classification) that results from inhibition of DNA synthesis during red blood cell production

syndrome defined by the presence of an ovarian tumour, right sided hydrothorax and ascites

Meig's syndrome

Skin receptor-->respond to light touch o Encapsulated body in the papillary dermis o Fast adapting discriminatory touch and vibration receptor Sits in the superficial dermis

Meissner corpuscles

Monoclonal antibody against IL-5 • Prevents eosinophil recruitment and activation • NICE approved for asthma • No clinical efficacy in hypereosinophilic syndrome

Mepolizumab

Skin receptor Slow adapting discriminatory touch and pressure receptor

Merkel cells

• usually metabolic effects • weight loss, lethargy • electrolytic disturbances e.g. small cell carcinoma = hyponatraemia, hypokalaemia, hypercalcaemia in Small Cell Cancer • finger clubbing

Non-specific features of lung cancer

Culture Direct detection➡includes detection of the whole organism, antigen or genomic material Immunological tests➡serology detects an antibody response

Methods of microbiological diganosis

• Cellular = less sensitive, cheaper and if negative always transplant • New ways = slightly too sensitive get antibodies up then can reject people when they need and would not cause too much of an immunological response if had transplant • Antibody detection = balance of clinical relevance and sensitivity

Methods to detect antibodies

Direct detection Culture Immunological tests (antibody detection)

Microbial diagnosis relies on 3 modalities

Pedunculated polyp as sits on a stalk, look at microscopic features of neoplasia from adenomatous Normal glands for basilar nuclei, all same size and shape, neoplastic not round glands, irregular shapes and nuclei = pseudostratified lining on top of one another and different in size and shape Around 85% of colorectal carcinomas is thought to follow the adenoma-carcinoma sequence Around 15% are due to microsatellite instability: completely different mechanism Loss of function of the DNA mismatch repair genes Tend to be female, right sided May show typical morphology: down the microscope, typical features associated: Pale material in mucin, mucinous poor differentiation poor infiltration by immune cells other pathways involved adenoma-carcinoma sequence and microsatellite instability = main ones

Microscopic features of colorectal cancer

• Intestinal type o Well or moderately differentiated o May undergo intestinal metaplasia and adenoma steps • Diffuse type o Poorly differentiated o Scattered growth o Cadherin loss/mutation • Most cancers are the well differentiated type • The less differentiated, the worse the prognosis First image is well differentiated (i.e. looks like tissue of origin so treatment can be targeted to this place) Second image is poorly differentiated

Microscopic subtypes of gastric adenocarcinoma

ESR CRP Ferritin Fibrinogen Haptoglobin Albumin Complement

Non-specific markers of systemic inflammation

o Fever "burning up" o Shaking episodes/chills o Sweating/night sweats o Feeling muddled/confused

Non-specific symptoms:

minimum concentration of antimicrobial agent at which visible growth is inhibited

Minimum inhibitory concentration (MIC)

Histology of malignant mesothelioma

Mixed tubulopapillary epithelioid & spindle cell sarcomatioid morphology Can be either type alone Can be poorly cellular - "desmoplastic" The main morphological differential diagnosis is malignant mesothelioma or non-small carcinoma Tubules and solid aggregates of malignant mesothelial cells The morphological differential diagnosis is adenocarcinoma or epithelioid malignant mesothelioma

neonatal meningitis and pneumonia

what does streptococcus agalactiae cause?

• Finger like projections of epithelial cells in the normal • Coeliac disease o Surface = flat o Villous atrophy o Crypt elongation o Increased IELs (intraepithelial lymphocytes) o Increased lamina propria inflammation • Sometimes not as obvious, a bit of flattening and some lymphocytes but need to double check with serology

Morphology of coeliac disease

Risk factors for intra-amniotic infections

Most common after prolonged rupture of membranes Other risk factors include: amniocentesis, cordocentesis, cervical cerclage, multiple vaginal examinations, Bacterial vaginosis Pathogenesis Bacteria present in the vagina cause infection by ascending through the cervix Haematogenous (via blood ) infection is rare e.g. Listeria monocytogenes

Staph and strep (gram positive) but anything is possible

Most common bugs that cause a brain abscess

K pneumoniae and other gram negative

Most common cause of hospital acquired pneumonia?

autoimmune destruction of the thyroid i.e. Hashimoto's thyroiditis

Most common cause of primary hypothyroidism

Epithelial tumours

Most common group of ovarian neoplasms (90%) 3 major carcinoma histologic types: Serous (tubal) Mucinous (endocervical) Endometrioid (endometrium) Each type contains benign/ borderline/ malignant variants Benign tumours subclassified based on components; cystic (cystadenomas), fibrous (adenofibromas), cystic and fibrous (cystadenofibromas) Malignant epithelial tumours -->cystadenocarcinomas

Viral meningitis causes

Most common infection of CNS especially in <1yr Enteroviruses (commonest, meningitis occurring in 50% of children <3mth ), HSV, Influenza, EBV, adenovirus, CMV Mononuclear lymphocytes in CSF Symptomatic treatment CP

carcinomas (come from the epithelial cells) more than 90% of the time

Most common primary malignant lung tumour

Chlamydia trochomatis

Most common sexually transmitted infection?

Insulinomas which can cause hypoglycaemia with the highest incidence between 40-60 years with females being more affected than males

Most common tumour arising from the islet of langerhans

Adenocarcinoma (malignant tumours of glandular tissue in epithelium) as there is columnar epithelium in the stomach

Most frequent gastric cancer

liver

Most frequent site for distant metastases of colon cancer

1 unit of red blood cells

Most of the plasma is removed to leave "concentrated red cells" Plasma is replaced by a solution of electrolytes, glucose and adenine to keep the red cells healthy during storage Haematocrit 60% 1 unit transfusion is expected to raise Hb by 10g/L

Inflammation of mucous membranes in the GI tract; often a side effect of radiation therapy or chemotherapy. Lasts about two weeks after stopping chemotherapy Risk factors: caries, periodontal diseases. Require a dental review before chemotherapy Increased risk of bacteraemia, principally Viridans streptococci Oral mucositis and intestinal mucositis (with diarrhoea) may occur together or separately No specific prophylaxis (preventative) medication is given for mucositis routinely but may be given antibiotics

Mucositis

- Enlargement of thyroid with varying degrees of nodularity - 1 or more thyroid nodules may be discovered by the patient or health care provider - Most patients are euthyroid (have a normally functioning thyroid gland) - Dominant nodule may be mistaken clinically for thyroid carcinoma - Tracheal compression or dysphagia may develop with large nodules

Multinodular goitre

o Often referred to as 'Acid Fast Bacilli (AFBs) o Do NOT stain using conventional gram staining o Mycobacterium tuberculosis - cause of TB o Other Mycobacterium species are sometimes referred to as 'Atypical Mycobacteria' and cause respiratory infections in those with chronic lung disease or opportunistic infections in immuno-compromised patients e.g. AIDS, transplant patients, etc

Mycobacterium species

Infects 1/3 of the world's population & is the most frequent infectious cause of death worldwide Most cases occur in the developing world (but are by no means limited to there) Infection is acquired by inhalation of infected respiratory droplets, the bacilli lodge in alveoli & multiply, resulting in the formation of a Ghon focus. Depending on the host's immune response the infection will either become quiescent or progress and/or disseminate. 90% of primary infections are asymptomatic The risk of disease progression is highest at the extremes of age and in the immunocompromised (inc. HIV) Reactivation of disease may occur later in life, particularly in the immunocompromised.

Mycobacterium tuberculosis

• TB in GI tract, mainly respiratory illness (night sweats, sputum etc) • May affect any bit of the GI tract with local symptoms: o Non healing oral ulcers o Gastric ulcers giving gastric outflow obstruction o Enterocutaneous fistulas • Ileo-caecal tuberculosis is the most common GI site, may be confused for a colonic malignancy • Before chemotherapy: 70% of patients with TB via aspiration developed GI TB with diarrhoea

Mycobacterium tuberculosis

One of the atypical organisms that cause pneumonia i.e do not have a cell wall Autumn epidemics every 4-8 years Commonest in children & young adults Main symptom is cough Diagnosis: serology (difficult to culture) Rare complications: pericarditis, arthritis, Guillain-Barre, peripheral neuropathy

Mycoplasma pneumoniae

Haematopoietic lineages

Myeloid: e.g. Granulocytes (White blood cells) Erythrocytes (Red blood cells) Platelets Lymphoid : e.g. B-Lymphocytes (White blood cells) T-lymphocytes (White blood cells

Ovarian metastatic tumours

Müllerian tumours (most common): uterus, fallopian tube, pelvic peritoneum, contralateral ovary Non-Müllerian tumours: Lymphatic/ haematogenous spread: GI tract: Large bowel, stomach (Krukenberg tumour), pancreaticobiliary Breast (lobular) Melanoma Less commonly, kidney and lung Direct extension: bladder, rectal Metastatic tumours are confirmed histologically; prognosis is typically poor

Herpes virus Adenovirus Parvovirus

Name some human DNA viruses

Rhabdovirus Togavirus Reovirus

Name some human RNA viruses

Methotrexate Infliximab Rituximab Sulfasalazine

Name some immunosuppressive drugs.

Dental infections Lung abscesses Colonic abscesses Post trauma skin/soft tissue infections Bacteroides species, fusobacterium species, prevotella species

Name some polybacterial infections and species which can cause them

o Penicillins - Benzylpenicillin, amoxicillin, flucloxacillin - Relatively narrow spectrum o Cephalosporins - Cefuroxime, ceftazidime etc. - Broad spectrum - Arranged into 'generations' o Carbapenems - Meropenem, imipenem - Extremely broad spectrum o Monobactams - Aztreonam - Gram-negative activity only - The ring is alone and is not fused to another ring

Name the four types of Beta-lactams and give examples and what thier spectrum is

Mouth Oesophagus Stomach Small bowel Large bowel

Name the non-sterile sites of the GI tract

Peritoneal space Pancreas Gall bladder Liver

Name the sterile sites of the GI tract

Adenosine analogues Guanosine analogues Abcavir Tenofovir

Name two purine analogues

Thymidine analogues-->zidovudine Cytsoine analogue-->lamvidine

Name two pyrimidine analogues

sore throat, rheumatic fever

what does streptococcus pyogenes cause?

• not very well understood • mutations in key genes regulating cell proliferation, DNA repair and apoptosis • squamous carcinoma: cigarette smoking is an irritant • squamous metaplasia -> dysplasia -> carcinoma in situ -> frank squamous carcinoma

Pathogenesis of lung cancer

more susceptibility to different autoimmune diseases, rejection

Negative of HLA molecules

Proportion of people with a negative test who do not have the target disorder

Negative predictive value

o Gram negative diplococcus o Cause of gonorrhoea o Ophthalmia neonatorum (neonatal conjunctivitis) o Can rarely cause invasive infections (e.g. septic arthritis) secondary to primary sexually transmitted infection

Neisseria gonnorhoea

o Gram negative diplococcus (pairs) o Causes meningococcal sepsis and/or meningitis o Classic presentation is of a purpuric non-blanching rash (sepsis) o Reduction in cases since the introduction of vaccination

Neisseria meningitidis

Cofactor for ATP Neuromuscular excitability Enzymatic function Regulates ion channels 0.5-1% bone matrix

Physiological importance of magnesium

syphilis

what does trepenoma pallidum cause?

Increased serum Ca and P Also has anti-cancer effects

Net effect of vitamin D

Neutropenia is when a person has a low level of neutrophils. Caused by: • Bacterial infections - e.g E. coli, S. aureus - often normal flora. e.g. Coag neg staph • Fungal infections - Candida spp. , Aspergillus spp. • Empirical therapy - Concept: broad spectrum antibiotics given as do not know exactly what pathogen is causing and will treat until tests come back which show which specific pathogen is causing o Pseudomonas can kill quickly in neutropenic patients therefore make sure is covered with AB • Treatment - broad spectrum. • e.g. Antipseudomonal penicillin +/- gentamicin, 2nd line treatment e.g. a carbapenem • fungi, viruses • Granulocyte stimulating factors (GCSF)

Neutropenic patients

• Qualitative - Chemotaxis - rare, congenital, e.g. inadequate signalling • Quantitative -Killing power - inherited, e.g. Chronic Granulomatous Disease. At risk of Staph. aureus infections Patient had granulomas disease therefore immunocompromised = spots located on the butt 'spotty botty'

Neutrophil defects

• Quantitative defects e.g. cancer treatment, bone marrow malignancy, aplastic anaemia - drugs o "Neutropenic" o Esp. imp. <0.5x10^9/L and if prolonged o >50% proceed to infection. High mortality o >50% those with Pseudomonal infections will die in 24hrs if not treated

Neutrophil lack

Clinical presentation of meninigits in children

Newborn & Infants: non-specific clinical presentation Fever Irritability Lethargy Poor feeding High pitched cry, bulging Anterior fontanelle Convulsions, opisthotonus (spasm of muscles causing backward arching of the head)

Is group B streptococci screened for in the UK?

No Until it is clear that antenatal screening for GBS carriage does more good than harm and that the benefits are cost-effective, the National Screening Committee does not recommend routine screening in the UK

the vocal folds close and you can't breathe

what happens if both recurrent laryngeal nerves are paralysed?

Nocardia is a genus of bacteria found in the environment Pulmonary nocardiasis is acquired through inhalation of the organism More common in the immunosuppressed & those with pre-existing lung disease (esp. alveolar proteinosis) - but still rare! Presentation & clinical/radiological findings are variable, making diagnosis difficult. Lung abscesses can develop The most suitable specimens are the sputum, or if necessary, broncho-alveolar lavage or biopsy. Treatment: as with all pneumonic infections- supportive Rx (ABC) & then antibiotics (several months). Co-trimoxazole most commonly used

Nocardia asteroides

• N0: no nodes involved • N1: 1-3 nodes involved • N2: 4/more nodes involved

Node staging

serum calcium level but magnesium can exert similar effects

what is the secretion of PTH physiologically controlled by?

o Pyrexia o Witnessed rigor/chills o Sweating o Confusion

Non specific examination findings:

• NAFLD = liver counterpart to metabolic syndrome • Insulin resistance results from excess of calorie intake over the body's demands • Fat is stored in the body in various compartments including the liver: depends on genetic factors • Stored in the liver = fatty liver or steatosis • Long term: excess calories + other factors some people develop steatohepatitis • Steatohepatitis = liver cell injury, inflammation and fibrosis due to liver cell stress, when the liver cell mitochondria start to be injured by the oxidative stress of too much energy transfer • Evolves slowly = reversible in early stages • If continuous for yrs = cirrhosis • Cirrhosis = cryptogenic as the microscopic features of fatty liver disease eventually disappear as the liver is completely remodelled • Risk of hepatocellular carcinoma developing due to cirrhosis

Non-alcoholic fatty liver disease consequences

Remove precipitating factors Remove pus and debris from the ear canal Analgesia

Non-antimicrobial management of otitis externa

• Rehydration: oral rehydration solutions and IV fluids • AVOID: o Antidiarrhoeals: loperamide, codeine o Delays clearance from bowel o Enhances tissue invasion o Prolongs fever o Increases risk of HUS in E coli O157 • Source isolation

Non-antimicrobial treatment for gastroenteritis

• Hyperplastic polyps: reactive, neoplastic • Hamartomatous polyps o Peutz-jeghers polyps o Juvenile polyps • Polyps related to mucosal prolapse o Inflammatory cloacogenic polyp o Inflammatory cap polyp o Inflammatory myoglandular polyp o Polypoid prolapsing mucosal fold • Post inflammatory polyps: pseudopolyps • Inflammatory fibroid polyp • Benign lymphoid polyp

Non-neoplastic polyps in the colo-rectum

Usually more cytoplasm Usually clumped/vesicular nuclei Usually more prominent nucleoli

Non-small cell carcinoma

Mucosae layer at the surface, test tube structures of epithelial cells Submucosa layer Splitting the mucosa layer and submucosa layer = thin bit of muscle = muscularis mucosae If cells break through from the mucosa into submucosa = cancer

Normal bowel histology

Nose: staph aureus Mouth: bruhing teeth can cause Viridans streptococci to enter the blood stream and damage heart valves causing endocarditis

Normal flora in different parts of the body

Mucosa--regenerative layer so is darker at the basal layer (which contains stem cells) and becomes flattened so there is less colour as they mature and move towards the surface Submucosa-->has mucous glands and is a layer of connective tissue Muscularis propria

Normal oesophageal histology

Normal: o Balance of aggressive (acid) and defensive forces o Surface mucous o Bicarbonate secretion o Mucosal blood flow o Regenerative capacity o Prostaglandins

Normal prevention of gastritis i.e. natural defences

Contains: Parenchyma contains heptaocytes➡makes up the bulk of the liver Portal tracts: tumours arise here typically (circled in green) which contains: -Bile ducts -Blood vessels -Fibroblasts -Inflammatory cells May contain primary tumours which can be benign/malignant These can arise from hepatocytes/bile ducts or other cells May contain secondary tumours

Normal structure of the liver

• Normal tissue: basic functions • O2 in, CO2 out • Tubes, air/blood interface, air pump, blood pump • Tubes mucus lined to collect and sweep out debris

Normal tissue of the lungs and basic functions

Malignant progression of hyperplasia

Normal-->non-atypical hyperplasia-->atypical hyerplasia (endometrial intraepithelial neoplasia)-->endometrioid adenocarcinoma Endometrial hyperplasia to endometrioid carcinoma is a progression from simple hyperplasia through complex to atypical hyperplasia and invasive carcinoma.. Simple hyperplasia is relatively common with endometriod carcinoma much less frequent. The chances of progression through the full spectrum increases the farther down the pathway the woman is. Caused by excess oestrogens from a variety of possible sources the first stage is simple hyperplasia where there is an overgrowth of the whole endometrium revealing a thick endometrium on ultrasound. In complex hyperplasia the proportion of the glandular epithelium increases and the epithelium can be folded into complex architectural patterns. With the onset of atypical hyperplasia (also called intraepithelial neoplasia) the cells show architectural changes of neoplasia with increased nuclear cytoplasmic ratio (bigger nuclei and less cytoplasm), irregular shapes, increased numbers of mitoses some of which may be abnormal.

• Not well understood Recurrent episodes of acute pancreatitis • Ductal obstruction by concretions (protein plugs) • Direct toxic effects - e.g. alcohol • Localised, irregular involvement of the gland early on, later global atrophy. • Dilated and distorted ducts • Calculi, esp in alcohol induced • Fatty replacement. Fibrosis Pseudocyst formation

Pathogenesis of chronic pancreatitis

Differentiated vulval intraepithelial neoplasia

Not graded Not HPV related occurs in chronic dermatoses especially lichen sclerosus Occurs in older women

9

Number of different human herpes viruses

• Nutritional support should consider: o Demands of hypermetabolic phase o Pre-trauma nutritional state • Nitrogen loss (peak at 4-8 days) o Long bone: 60-70g muscle protein o Severe burns: 300g muscle protein • Immobilisation incs losses o Calcium, phosphate, magnesium etc. • Nutrition is crucial in helping patients through hyper-metabolic phase and preparing for anabolic recovery o Ambient temperature o Use the gut if possible: nasogastric tubes o TPN: to administer trace elements, fat soluble vitamins

Nutrition and recovery after trauma

glycated haemoglobin HbA1c

what is used to assess degree of long term glycaemic control?

• Same pathological spectrum as alcoholic liver disease • Steatosis, steatohepatitic, cirrhosis, HCC (hepatocellular carcinoma) • Associated with metabolic syndrome: obesity, T2DM, hyperlipidaemia, some drugs • Now recognised to be the commonest cause of liver disease • Treatment: address the causes of metabolic syndrome • Big public health issue: 2016 NICE guidelines on NAFLD and cirrhosis, manage patients in primary care whenever possible

Obesity: Non-alcoholic fatty liver disease

Localised or diffuse obstruction of airflow

Obstructive pulmonary disease

What is acute haemolytic transfusion reaction?

This occurs when there is a transfusion of red blood cells to someone who has preformed antibodies against antigens that are expressed on the transfused red blood cell Free Hb is released in the circulation

• 8th most common cancer in the world • two main histological types: o squamous cell carcinoma o adenocarcinoma • distribution varies around the world: o UK 30% squamous, mainly adenocarcinoma due to lifestyle (obesity, Barrett's oesophagus) o China/Japan >95% squamous (eastern populations, obesity lower, then the vast majority are squamous)

Oesophageal carcinoma

• Effort rupture of the oesophagus, or Boerhaave syndrome, is a spontaneous perforation of the oesophagus that results from a sudden increase in intraoesophageal pressure combined with negative intrathoracic pressure (e.g.severe straining or vomiting). • Rupture of the intrathoracic oesophagus results in contamination of the mediastinal cavity with gastric contents • This leads to chemical mediastinitis with mediastinal emphysema and inflammation, and subsequently bacterial infection and mediastinal necrosis

Oesophageal rupture

• Inflammation of the oesophagus • Classification: acute or chronic (depends on aetiology and duration)

Oesophagitis

-Monoclonal anti-IgE antibody. Binds mostly unbound serum IgE and blocks binding to FcεRI. -Used in allergic asthma resistant to inhaled steroids and long-acting β2-agonists. • NICE approved for chronic urticaria and angioedema • May cause severe systemic anaphylaxis

Omalizumab

fungal infection of the nail Thickening, discolouring, dystrophy of the nail, there are four main types: -Lateral/distal subungual Superficial white-usually in immunocompromised Proximal Total nail dystrophy

Onychomycosis

o Bone and joint infection o Pyelonephritis o Empyema (lung abscess) o Febrile neutropenia in cancer patients

Oral antibiotics have been shown to be just as effective as IV antibiotics for infections like?

Cold sores Usually asymptomatic

Oral herpes simplex virus

• Solid organ transplants - Liver in paracetamol overdose • Stem cells in haematological malignancy. • Anti-rejection treatment suppresses cell mediated immunity to stop effects of cytotoxic and natural killer cells. Degree of immunosuppression varies on how closely the donor and recipient are matched and organ involved.

Organ transplantation

B lymphocytes

Part of the adaptive immune system Rearrange immunogloblulin genes to enable antigen specific antibody production Humoral immunity

o Salmonella spp o Campylobacter spp o Escherichia coli (EHEC or VTEC 0157)

Organisms which can cause non-foodborne gastroenteritis

o Rotaviruses o Norwalk virus o Noroviruses o Adenoviruses o Astroviruses o Caliciviruses o Parvoviruses

Organisms which can cause viral gastroeneteritis

o Staphylococcus aureus o Bacillus cereus o Clostridium perfringens o Clostridium botulinum o Escherichia coli (ETEC, EPEC, EHEC (or VTEC 0157) , EAEC, EIEC) o Salmonella spp o Shigella spp o Campylobacter spp o Yersinia enterocolitica o Vibrio parahaemolyticus o Listeria monocytogenes o Aeromonas hydrophila o Plesiomonas spp

Organisms which cause foodborne gastroenteritis

o Giardia lamblia o Entamoeba histolytica o Cryptosporidium parvum o Vibrio cholerae

Organissm which can cause waterborne gastorenteritis

T lymphocytes

Part of the adaptive immune system There are multiple sub-types e.g. CD4 Rearrange the T cell antigen receptor Part of cell mediated immunity Target-specific cytotoxicity Interact with B cells and macrophages Regulate immune responses

• Lack of mineralisation of bone • Not enough calcium or phosphatase then cannot mineralise the bone • Adult form - widened osteoid seams with lack of mineralisation • Classic childhood rickets - widened epiphyses & poor skeletal growth • Causes of osteomalacia: • Insufficient calcium absorption from intestine • Due to lack of dietary calcium or Vit D deficiency/resistance, possibly low calcium and high pTH as body tries to compensate = second hyperparathyroidism • Excessive renal phosphate excretion • Rare genetic forms (e.g. hereditary hypophosphataemic rickets)

Osteomalacia

High alk phos, low Vit D, possibly low Calcium and high PTH (secondary hyperparathyroidism)

Osteomalacia investigations would reveal..

Decreased bone mass + deranged bone micro architecture = failure of structural integrity

Osteoporosis equation

• CVID: common variable immune deficiency • IgA deficiency: do not produce, quite common, more prone to autoimmune disease • X linked hyper IgM syndrome: mount an immune response usually produce IgM first and IgG later, cannot switch from M to G so have high levels of IgM • Transient hypogammaglobulinaemia of infancy: do not produce antibodies till 3-4months, last trimester then antibodies come from mother, take immunoglobulin levels but they do not have any at 3-4 months as they have not started producing their own

Other B cell defects

Prevents HIV virion from entering the cell - Enfuviritide (T20, given by IM injection)—fusion inhibitor - Maraviroc—chemokine receptor antagonist (co-receptor CCR5)

Other HIV drugs include entry inhibitors. What do these do? Give 2 examples

Block the action of integrase which is a viral enzyme that inserts the viral genome into the DNA of the host cell Raltegravir and Dolutegravir

Other HIV drugs include integrase inhibitors. What do these do and give two examples

• Methotrexate (MTX): folate antagonists • Cyclophosphamide: cross link DNA

Other antimetabolites and cytotoxic drugs

Carcinoid tumours - low grade malignant tumours, better survival Malignant mesenchymal tumours - very rare, most common type is synovial sarcoma Primary lung lymphomas - rare, can be seen in HIV/AIDS patients

Other primary malignant lung tumours

• Perforated ulcers which allows the tumour cells into the abdominal cavity • Invading another part: caecum or another part of the bowel

Other types of cancer with T4 tumour stage

The ear canal is the only skin-lined cul-de-sac in the body OE = inflammation of the external ear canal presenting with a combination of: otalgia, pruritus and non mucoid ear discharge. Symptoms < 3/52 = acute OE Symptoms >3/52 = chronic OE

Otitis externa (OE)

Middle ear inflammation. Fluid present in middle ear. V. common in children Uncomplicated acute OM is defined as: mild pain <72hours duration and an absence of severe systemic symptoms, with a temperature of less than 39°C and no ear discharge. Complicated acute OM is defined as the presence of: severe pain, perforated eardrum and/or purulent (pus producing) discharge, bilateral infection, mastoiditis. Organisms: Viruses! Streptococcus pneumoniae, Haemophilus influenzae & Moraxella catarrhalis Swab any pus Treatment: if not unwell watch and treat symptomatically (analgesia, decongestant etc.) and review early. If unwell - amoxicillin

Otitis media

CLEAN

what method of cleaning would you use for devices that only contact intact skin?

o Outcomes depend on the stage at diagnosis o Currently only 20% live for 5yrs after diagnosis, presented with advance or metastatic usually o Small progress and improvement over the years but very gradual o More effective chemotherapy and identify tumours at an early stage if we want to make significant improvements to patient survival

Outcomes for gastric cancer

Blood cell function

Oxygen transport Coagulation (haemostasis) Immune response to infection Immune response to abnormal cells (senescent, malignant etc)

Tail of the pancreas

what part of the pancreas are mucinous lined cysts found?

• Adenomas: benign o Single adenoma account for 85% of cases of primary HPT - Ectopic adenomas • Rarely ectopic adenomas in mediastinum o Some parathyroid adenomas found in thymus gland: parathyroid cells which migrated during embryogenesis • Glandular hyperplasia o 6-10% of cases of HPT o all 4 parathyroid glands enlarged o can occur sporadically/ part of genetic syndromes • Parathyroid carcinoma (malignant) o 1-2% of all cases of hyperparathyroidism o features of invasion on histology o usually aggressive disease, with significant hypercalcaemia and possibility of distant metastases

PHPT (Primary hyperparathyroidism) adenomas

Risk factors of a DVT

PMHx of DVT or PE, FHx, Recent Surgery, Cancer, Immobility, Pregnancy, BCP, Smoking, LE Trauma, LE Casts

autosomal dominant cause of hereditary pancreatitis

PRSS1 inherited mutation

a skin receptor cell type that detects vibration and deep pressure Encapsulated bodies in the deep skin Fast adpating for rapid vibration This is the bottom receptor

Pacinian corpuscle

• Rapid bone turnover and formation • Leading to abnormal bone remodelling • Mainly over 50 years old • Higher prevalence in men • Probable genetic and environmental triggers: do not know what causes it e.g. viral trigger • FH in 10-15% of cases • Polyostotic (many bones) or monostotic (one bone) • Occurs in the brain then can cause damage to the cranial nerve • Elevated alkaline phosphatase reflecting increased bone turnover This result in unshaped bones and chaotic reorganisation of bone

Paget's disease

• 3% of all cancers: 10th most common • >7000 cases UK • most common type of pancreatic cancer: up to 90% of all pancreatic neoplasms • 5 yr survival 4% • 60-80yrs, rare before 40yrs • 1.3Male: 1 female

Pancreatic adenocarcinoma

• reaction to gliadin o alcohol soluble component of gluten o contains most of the disease producing components o induces epithelial cells to express IL-15 • inc CD8+ intraepithelial lymphocytes (IELs) o IL15 produced by the epithelium à activation / proliferation of CD8+ IELs o These are cytotoxic and kill enterocytes, damage epithelial lining of the small bowel o Immune response to gliadin o CD8+ IELs do not recognise gliadin directly o Gliadin-induced IL15 secretion by epithelium is the mechanism

Pathogenesis of coeliac disease

• Present for at least a decade before detected • Pancreatic carcinoma has an ill defined border • Early cancer is silent, most patients with symptoms have advanced disease • Non-specific symptoms -epigastric pain, radiating to back • Weight loss, painless jaundice, pruritis and nausea. • Trousseau's syndrome (migratory thrombophlebitis) and Courvoisier's sign (palpable gallbladder without pain, so you know it's not due to stones) • Distant metastases: liver, peritoneum, lung (liver is the most common site of distant metastasis) • Diabetes - increases risk and can be a presenting complication, however this is common in older population but if it has a quick onset this can be a sign • Almost universally fatal (incidence nearly equals mortality) • Mean survival untreated is 3-5 months • 10-20 months post- surgery but only 10-20% are resectable at the time of diagnosis

Pancreatic carcinoma

• endocrine secretions: islets of Langerhans o insulin, glucagon o pancreatic polypeptide • exocrine secretions: ductal and acinar cells o bicarbonate to neutralise acid o digestive enzymes - trypsin, chymotrypsin and elastase - carboxypeptidases - amylase - lipase

Pancreatic function

tests to measure pancreatic function, including serum amylase or lipase, a test for the amount of fat in the stool, and an X-ray of the anatomical features of the pancreas and common bile duct • Direct (Invasive) Tests o Intubation to collect aspirates in the duodenum. o Secretin, CCK, Lundh Tests • Indirect (Non-invasive) Tests o Pancreatic enzyme analysis in stools (Elastase) o Trypsinogen (IRT) measured in blood in CF screening o Pancreolauryl & NBT-PABA tests

Pancreatic function tests

• uncommon <3% pancreatic neoplasms • derived from islet cells • present with a wide range of clinical symptoms: depending upon their endocrine effects • spectrum of behaviour: from benign to malignant • Incidence <1 per 100,000 per year • Autopsy studies - higher incidence (up to 10%) suggesting often occult • Recent increasing incidence - prob related to improvements in imaging and increased awareness • 20-60 years • M=F • Increased risk MEN (multiple endocrine neoplasia) 1: pituitary adenoma, parathyroid adenoma, islet cells tumours of pancreas • Usually well circumscribed i.e. have a definitive shape and border, sometimes encapsulated • Solid • 10->50mm • occur anywhere in pancreas • Can be a yellow colour • can be multiple

Pancreatic neuroendocrine tumours

• Pancreas very large organ, secretes digestive enzymes and produces enzymes that flow in one direction and stop bacteria and pathogens getting in, obstruction due to physical or stasis then enzymes cannot get into GI tract, auto-digestion of the organ, destruction of pancreas • Complications: o Necrotising pancreatitis 15% o Peripancreatic fluid collection Pancreatic pseudocyst o Acute necrotic collection o Walled-off necrosis • All can be infected with enteric bacteria • Surgery: Debridement and antibiotics: • Common pathogens: streptococci, yeasts, enterococcus

Pancreatitis

• inflammation (itis) of the pancreas • associated with injury to the exocrine parenchyma • acute: gland reverts to normal if underlying cause removed • chronic: irreversible loss of the pancreatic tissue

Pancreatitis

Most common type of thyroid carcinoma accounting for more than 70% of thyroid cancers o Female predominance 1.5:1 o Wide age range with a mean of 43 years o Familial, autosomal dominant non-medullary thyroid carcinoma o FAP o Cowden's syndrome-->Cowden syndrome is a disorder characterized by multiple noncancerous, tumor-like growths called hamartomas and give an increased risk of developing certain cancers. o Therapeutic irradiation o Radiation exposure o Activation of RET or NTRK1 o Variety of chromosomal translocations or inversions o Fusion of RET tyrosine kinase regions with constitutively expressed thyroid proteins eg PTC1 in inv(10)(q11;q21). PTC2 t(10;17(q11.2;q21) o BRAF V600E mutation o RAS mutations

Papillary carcinoma of the thyroid

Viral pathogens which cause pneumonia in 4 month to 5 year olds

Parainfluenza virus 1 and 4 Adenovirus Influenza viruses A and B

o Potentially life threatening because of possibility of involving the carotid sheath and its vital contents - Carotid sheath: Common carotid artery, internal jugular vein, vagus nerve o Propensity for airway impingement o Bacteraemic dissemination o Clinical presentation: dominated by the symptoms and signs of primary source of infection o Diagnosis of parapharyngeal space involvement is often delayed o Dental infections = most common underlying cause

Parapharyngeal space infections

4 species of plasmodium: • P. falciparum (most clinically significant) • P. vivax • P. ovale • P. malariae MICROPARASITE (protozoa-sporozoan)

Pararsite that causes malaria

an organism which lives on another organism (its host) and benefits by deriving nutrients at another's expense

Parasite

Ascaris lumbricoides-->intestinal nematode MACROPARASITE

Parasite that causes ascariasis

S. haematobum S. mansoni S.intercallatum S. japonicum S. mekongi These are all helminths: platyhelminth--trematode/fluke MACROPARASITES

Parasite that causes shistosomiasis aka Bilharzia disease

Trichomonas vaginalis This is a flkagellated protozoan MICROPARASITE

Parasite that causes trichomoniasis

Giardia lamblia Flagellated protozoa MICROPARASITE

Parasite which causes giardiasis

host where the remains viable without further development

Paratenic host

Most common cause of primary hyperparathyroidism o An encapsulated benign neoplasm of parathyroid cells. o 1 per thousand people. o Symptoms of hypercalcaemia. o Association with MEN1 and MEN2 syndrome and hyperparathyroidism and jaw tumour syndrome. o Single enlarged parathyroid gland; remaining glands suppressed and small.

Parathyroid adenoma

- uncommon - looks like a adenoma - 1% can cause hyperparathyroidism o Malignant tumour derived from parathyroid parenchymal cells o Only 1% of primary hyperparathyroidism o Symptoms referable to excess calcium o Indolent with recurrences common (about 50% o 50% 10 year survival o Treated with surgery

Parathyroid carcinoma

• Secreted by chief cells of parathyroid gland • Polypeptide containing 84 AAs • In the low power magnification a round, encapsulated organ is seen. • Within the gland there is a lot of adipose tissue and numerous venules, which run through the gland that are filled with red blood cells. These are seen either in cross section or longitudinal section. • The parathyroid gland has two cell types, chief cells and oxyphil cells. Chief cells are more numerous and have a round nucleus surrounded by a small amount of cytoplasm. Chief cells produce PTH. • The oxyphil cells are seen in scattered groups among the chief cells. They have a slightly smaller nucleus and eosinophillic cytoplasm. • The function of the oxyphil cells is unknown.

Parathyroid hormone

difference between the causes of parietal pleural fibrous plaques and diffuse pleural fibrosis?

Parietal pleural fibrous plaques--Low level of asbestos exposure Diffuse pleural fibrosis--high level asbestos dust exposure

o Epidemiology: - Spring time=peak - 50% infected by 15 years, 90% by 90 years o Mode of transmission: - Droplet transmissions from respiratory route - Infects and kills erythrocyte progenitor cells—causing transient anaemia o Important clinical syndromes: 1. Erythema infectiosum = fever, coryza, fiery red rash to cheeks, 'lacy' rash to body 2. Transient aplastic crisis affects those with high erythrocyte turnover e.g. sickle cell, thalassemia *** 3. Infection in pregnancy - 7-10% fetal loss if maternal parvovirus infection in first 20 weeks - 2-3% develop hydrops fetalis: severe fetal anaemia → oedema, ascites, heart failure

Parvovirus B19-->slapped cheek syndrome/ fifth disease

the short-term immunity that results from the introduction of antibodies from another person or animal. • transfer of specific, high-titre antibody from donor to recipient. Provides immediate but transient protection • Problems o Risk of transmission of viruses o Serum sickness • Types o Pooled specific human immunoglobulin o Animal sera (antitoxins an antivenins) • Uses o Hep B prophylaxis and treatment o Botulism, VZV (pregnancy), diphtheria, snake bites

Passive immunity

• PRRs: recognise conserved pathogen associated molecular patterns (PAMPs) which are unique to each pathogen • PAMP example: Lipopolysaccharide • Phagocytes use PRRs to detect pathogens • Different PRRs e.g. TLRs, RLHs, NLRs • Toll like receptors are a type of PRR o TLR4: lipopolysachharide o TLR5: flagellin o TLR3: viral RNA, defects lead to reccurent HSV encephalitis • Cascade of events involving various molecules intracellularly -> production of inflammatory cytokines o Occurs everytime a pathogen enters the body o MyD88 and IRAK4 are involved in this cascade: recognised the bacterium and got to eat it and release inflammatory mediators = more immune response

Pathogen recognition receptors

- white males - association with GO reflux - no association with H pylori/ diet - increased incidence in recent yrs

Pathogenesis of carcinoma of the gastro-oesophageal junction

o increased intra-luminal pressure - irregular, uncoordinated peristalsis - overlapping (valve like) semicircular areas of bowel wall o points of relative weakness in the bowel wall - penetration by nutrient arteries (vasa recta) between mesenteric and antimesenteric taenia coli - age related changes in connective tissue

Pathogenesis of diverticulosis of the colon

o Trigger - > inflammatory mediators, type 1 hypersensitivity o Inflammatory mediators, type 1 hypersensitivity o and/or neural stimulation -> muscle spasm and mucus secretion and mucosal inflammation & oedema o narrowed airways most problems as exhale since pulled open during inhalation o Tubes narrowed/ blocked o Essentially a type 1 hypersensitivity reaction o Key players: - IgE - Mast cells - Eosinophils - Histamine, cytokines Allergen - dust, pollen, animal products Cold, exercise, reparatory infections Many different cell types and inflammatory mediators involved Degranulation of IgE bearing mast cells histamine initiated bronchoconstriction & mucus production obstructing air flow eosinophil chemotaxis

Pathogenesis of Asthma i.e. how does the abnormal tissue come about?

-Escape of pancreatic juice from the ducts into the pancreatic tissue -Pancreatic digestive enzymes cause destruction and severe hemorrhage -Resulting build-up of pancreatic juice increases pressure within the duct system, causing ducts to rupture • Varies according to aetiology • Leakage and activation of pancreatic enzymes • Amylase released into blood • Mild pancreatitis: swollen gland with fat necrosis • Severe: swollen, necrotic gland with fat necrosis and haemorrhage • Grey Turner's sign: haemorrhage into the subcutaneous tissues of flank • Associated with extensive haemorrhage • Cullen's signs: periumbilicus • Hypocalcaemia: fatty acids bind calcium ions, hyperglycaemia, abscess formation, pseudocysts • Obstruction e.g. stones: damages duct lining resulting in leakage and activation of pancreatic enzymes. Hypoxia affects the acinar cells at periphery of lobules. • Fat necrosis: chalky white material containing calcium salts which have been freed up by lipase mediated cleavage of fatty acids

Pathogenesis of acute pancreatitis

- association with H pylori - association with diet (salt, low fruit and veg) - no association with GO reflux - decreased incidence in recent yrs

Pathogenesis of carcinoma of gastric body or antrum

depends on site of cancer

Pathogenesis of gastric cancer depends on

One of sufficient virulence and in adequate numbers to cause disease

Pathogenic organism

When would you NOT tranfuse fresh frozen plasma?

To treat a single factor deficiency To correct abnormal clotting results in patients that are not bleeding To reverse warfarin

• Clinical spectrum: consequence of the amount of hepatocytes that are injured/ killed and how well the remaining ones can regenerate • Rare severe end: hepatocytes die faster than they can be replaced and result in rapidly progressing organ failure and possibly death • Liver transplantation is necessary to save the life of a patient with severe acute liver failure = rapid progression from coagulopathy, encephalopathy (confusion, coma) • Most common to very rare: o Asymptomatic o Malaise o Jaundice o Coagulopathy o Encephalopathy o Death • Depends on how many hepatocytes are damaged at once, and how good the liver is at regenerating • Pathology: cell death, inflammation and regeneration

Pathology of acute hepatitis

• injury to liver cells, inflammation, formation of scar tissue and regeneration of hepatocytes: non-specific features of injury • specific pathological features depend on the cause of injury • use of liver biopsy in diagnosis: o to determine the cause of the damage: specific features, if present o to assess the stage of disease: how much scarring, spectrum from normal to cirrhosis • Diagnosis: liver histology in conjunction with the results of other investigations • There may be more than one cause of liver injury: alcohol and metabolic syndrome = common • Stage of chronic liver disease refers to the progression on a continuous spectrum from normal to cirrhosis

Pathology of chronic liver disease

Cerebral abscess

Patient with endocarditis presents with increasing confusion and a reduced state of consciousness. What may they present with in the brain?

What is pleurodesis?

Pleurodesis is the infusion of an irritative agent, such as bleomycin or talcum powder, into the pleural space. This inflames the pleura, causing fibrosis so the lung will stick to the chest wall. When the pleural space is eliminated, the effusion cannot reaccumulate to prevent fluid or air from continually building up around your lungs

• Haemorrhage: acute (large vessel: large bleed into the stomach, start throwing up blood, smaller vessel = anaemia) and/ chronic leading to anaemia • Perforation = peritonitis o Very unwell with this • Penetration into an adjacent organ e.g. liver or pancreas o Inflammation and causes to stick to another organ and therefore no leakage of gastric leak into abdominal cavity but into another organ • Stricturing = hour glass deformity o Narrowing at the centre of the stomach due to healing o This results in difficulty swallowing and vomiting what they eat because food has to pass through the narrowing

Peptic ulcer complications

Not treating H. Pylori can lead to a peptic ulcer Localised defect extending at least into the submucosa of the stomach or duodenal lining If only part of the lining is affected this is an erosion If the full lining is affected this is an ulcer

Peptic ulcer disease

- May be focal or diffuse and presents as a red, fluctuant swelling of the gingiva, which is extremely tender to palpation - The abscesses always communicate with a periodontal pocket from which pus can be readily expressed after probing - Requires surgical drainage

Periodontal abscess

Originally defined as the non neoplastic lung diseases due to inhalation of mineral dusts in the workplace Now also includes organic dusts, fumes and vapours

Pneumoconioses: 'the dust diseases'

bone and liver

what produces ALP?

Plaque beneath the gingival margin o May progress to orofacial space infections o Associated with increased detection of anaerobic bacteria • Inadequate oral hygiene e.g. no interdental cleaning = bacterial infection of gingival margin: gum bone interface • Normally results in gingivitis and can progress to periodontitis • Gingival inflammation with accompanying loss of supportive connective tissues including alveolar bone (pockets > 5mm) defines periodontitis • Alveolar bone is the thickened ridge of bone that contains the tooth sockets (dental alveoli) on bones that hold teeth • Periodontal infection can progress to an acute condition called Vincent's angina (trench mouth) or infection can spread within the soft tissue structures in the mouth, which can themselves lead to deep neck space infections Gingivitis Periodontitis Periodontal abscess Acute necrotising ulcerative gingivitis

Periodontal infection

Collection of pus or fluid around the tonsil o Unilateral swellings of the tonsil o Caused by Streptococcus pyogenes (group A strept) o Symptoms: - painful swallowing - Unilateral sore throat - Ear ache o Signs: - Muffled voice - Trismus: lock jaw - Unilateral deviation of the uvula towards the unaffected side - Soft palate fullness or oedema - The oral airway may be compromised - Drooling o Treatment: Surgical drainage and antibiotic management

Peritonsillar abscess (quinsy) What is it? Symptoms Signs Treatment

- bronchiolar wall smooth muscle hypertrophy - mucus gland hyperplasia - respiratory bronchiolitis leading to centrilobular emphysema

Persistent or irreversible changes in asthma

Hamartomatous (benign) polyps throughout GI tract and mucocutaneous hyperpigmentation (freckle-like spots) on lips, oral mucosa, and genital skin; autosomal dominant disorder • always inherited, never sporadic • autosomal dominant condition: mutation in STK11 gene on chr 19 • prevalence: 1 in 50,000-1 in 120,000 births • present clinically in teens or 20s with abdominal pain: intussusception, gastro-intestinal bleeding, anaemia = inc risk of cancer • multiple gastro-intestinal tract polyps: predominantly small bowel o can see in stomach, colon, urinary bladder, nose • muco-cutaneous pigmentation: 1-5mm macules peri oral, lips, buccal mucosa, fingers and toes

Peutz-Jeghers syndrome

o Catecholamine-secreting tumour arising from adrenal medulla. o 8 per million of population. o 10% bilateral, 10% extra-adrenal, 10% malignant, 10% familial and 10% in children. o Most are sporadic but familial syndromes MEN2a and 2b, von Recklinghausen's disease and von Hippel-Lindau disease o symptoms of hypertension, palpitations, headaches, anxiety. o Elevated urine catecholamines, adrenaline, noradrenaline. o Excellent prognosis when benign and properly managed surgically. o Malignant tumour may pursue an aggressive course

Phaeochromocytoma

• Commonly caused by viruses, however in a third of people, no cause can be found. • Common infectious causes include: o Viruses: - Rhinovirus, Coronovirus, Parainfluenza, Influenza (A & B), Adenovirus etc. Viruses account for ~50% and are the most common cause of sore throat. o Bacteria: - Group A beta-haemolytic Streptococcus (GABHS) is the most common bacterial cause of sore throat. (15-30% of sore throats in children, and 10% in adults). • Rare causes: o Neisseria gonorrhoeae (Gonococcal pharyngitis) o HIV-1 (can be the first presentation of HIV infection) o Corynebacterium diphtheriae (Diptheria)

Pharyngitis and tonsillar pharyngitis causes

Phase 1: Shock • Develops within 2-6hrs after injury • Lasts 24-48hrs • Cytokines, catecholamines and cortisol secreted • Inc heart rate: tachycardia • Inc respiratory rate o Peripheral vasoconstriction: selective peripheral shut down to preserve vital organs • Primary aims: stop bleeding, prevent infection

Phase 1 after trauma

Associated with trauma (including ear piercing & acupuncture), surgery or burns Perichondritis: may be a complication of high ear piercing (puncture through the cartilage of the upper third of the pinna) A swab of the area and blood cultures (if in secondary care) should be obtained prior to starting antibiotics Usual infective agent(s) in auricular perichondritis: Pseudomonas aeruginosa and/or Staphylococcus aureus Empirical treatment: ciprofloxacin + flucloxacillin (or vancomycin if penicillin allergy)

Pinna cellulitis

Phase 2: Catabolic state • Develops approx. 2 days after injury • Necessary for survival but if persists or is severe = inc mortality • Catecholamines, glucagon, ACTH - > cortisol • Inc oxygen consumption • Inc metabolic rate • Inc neg nitrogen balance: skeletal muscle breakdown to release amino acids • Inc glycolysis: skeletal energy reserve depleted • Inc lipolysis: adipose tissue breakdown to release fatty acids • Primary aims: avoid sepsis, provide adequate nutrition

Phase 2 after trauma

Phase 3: anabolic state • Occurs approx. 3-8 days after uncomplicated surgery • May not occur for weeks after severe trauma and sepsis • Coincides with beginning of diuresis and request for oral intake • Gradual restoration of: o Body protein synthesis o Normal nitrogen balance o Fat stores o Muscle strength • Aims: o Adequate nutrition supply is critical in this phase o Refeeding syndrome risk o May last a few weeks or a few months o Obesity paradox --> patients who are overweight at the time of trauma tend to recover more quickly because they have more energy stores

Phase 3 after trauma

Meningococcemia

Pink macules and papules, petechiae, hemorrhagic petechiae, hemorrhagic bullae, purpura fulminans MORTALITY 5-10% (90% if DIC) MORBIDITY 10% (Deafness, neurological problems, amputations) Peak incidence < 4yrs Immunisation programme includes Men C 60% of bacterial meningitis in UK due to Men B Fever, non-specific malaise, lethargy, vomiting, meningism, resp distress, irritability, seizures Maculopapular rash common early in disease Petechial rash seen in 50-60%

A common fungal infection that causes small, discoloured patches of skin. o Hyper- or hypopigmented lesions o Upper trunk o Between puberty and middle age o More common in tropics o Relapsing

Pityriasis versicolor

2 ways platelets are collected

Platelets are collected in two ways: Pooled platelets: 1 unit of platelet is produced from a unit of whole blood. 4-6 of these units (from different donors) are pooled together in a single pack Apheresis platelets: As blood cycles through apheresis machine, platelets are removed and all other blood constituents are returned to the donor. The amount of platelets collected with this procedure represents the equivalent of 4-6 units of random donor platelets Plataelts have the advantage of being collected from a single donor to reduce the risk of disease transmission

Describe platelets

Platelets are derived from bone marrow megakaryocytes ~ 200 x10^9/litre Together with soluble plasma clotting factors and endothelial cells form part of the blood clotting system Aggregate to plug holes in damaged blood vessels

Effect of asbestos on the pleura

Pleural effusion Parietal pleural fibrous plaques Diffuse pleural fibrosis Malignant mesothelioma - 2567 UK deaths in 2014

Most common infection in people with AIDS caused by organism: P. jiroveci **PREVENTION**-prophylactic therapy **Diagnosis** Definitively identified by identifying organism in lung tissue through sputum induction, bronchial-alveolar lavage, and trans-bronchial biopsy Is a fungus! But lacks ergosterol in its cell wall & is not susceptible to a number of antifungals. Ubiquitous in the environment Principle mode of transmission is airborne route Pneumonia: insidious onset of fever, dyspnoea, non-productive cough & reduced exercise tolerance. Exercise induced hypoxia is a classic finding. Specimens: rarely isolated from expectorated sputum, can be found in induced sputum, broncho-alveolar lavage increases the diagnostic rate. PCR to detect P.jiroveci DNA has overtaken immunofluorescence techniques. Supportive care, antimicrobials (including co-trimoxazole) and steroids. Some at risk groups including HIV-infected patient with a CD4 count <200 get primary prophylxis.

Pneumocystitis pneumonia

• Pneumonia is a clinical diagnosis based on respiratory symptoms, signs and chest XR changes • Severity assessment CAP= C(U)RB65- score out of (4)5 o CRP may help guide diagnosis and antibiotic need o Low (0-1): No investigations required (NICE CG191) o Mod-Severe (2-5): Sputum, Blood Cultures, Atypical Screen o Atypical Screen= Urine for Legionella antigen; Nose/throat for Mycoplasma PCR. Might include Serum

Pneumonia

3-5% Pleural effusion: - clear fluid +/- pus cells +/-organisms 1% Empyema: pus in the pleural space (-loculated) Lung abscess: - suppuration + destruction of lung parenchyma - single (aspiration) anaerobes, Pseudomonas - multiple (metastatic) Staphylococcus aureus

Pneumonia complications

Raised red blood cells

Polycythaemia

• extension of tumour outside the pancreas • metastatic spread to local lymph nodes • vascular and perineural invasionprominent cause of death • poor differentiation • positive margins on resection

Poor prognostic factors of a pancreatic adenocarcinoma

Do not look like the tissue of origin o Rare o < 1% of all pancreatic tumour o 2-3% of all pancreatic endocrine tumours o Males > Females o 40-75 years o Advanced disease at presentation o Prognosis without treatment 1-2 months, with chemotherapy up to 50 months

Poorly differentiated neuroendocrine tumours

Proportion of people with a positive test who have the target disorder

Positive predictive value

• Immediate: potential mortality o Intravascular fluid loss o Extravascular volume-->accumulation of fluid into an extravascular space o Tissue destruction o Obstructed/ impaired breathing • Starvation • Infection • Inflammation

Possible features of physical trauma

o Start antibiotics early, and look to stop/de-escalate early o Delay antibiotics-with plan for how/when to access/start antibiotics e.g. delayed prescription o Start broad, and look to narrow o Start narrow, and have a plan for how/when to broaden

Possible strategies of when to start antibiotics

term used to desrcibe the time after widespread antibiotic resistance has reduced the availability of antibiotics to treat infection

Post antibiotic era

o Increased risk of diabetes o Repeat fasting glucose or Hba1c 13 weeks after delivery o Then perform annual diabetes screening checks

Post pregnancy gestational diabetes

Obstruction of the common bile duct Bilirubin is conjugated, soluble and capable of being excreted but can't get into the gut (duodenum)-->patient notice yellow eyes, pale stool and dark urine Pale stool-->bile duct obstruction so bile cannot colour faeces The site of abnormality of bilirubin excretion can be deduced from the clinical history, colour of the skin, faeces and urine

Post-hepatic jaundice

Refers to an infection resulting from a procedure • Superficial Surgical Site Infection: SSI-S • Deep Surgical Site Infection: SSI-D • Organ space SSI: SSI-O • Within 30 days of surgery or 1 year if prosthetic infection • Terms used for post-operative surveillance

Post-operative infection

• Biomarker of poor outcome • Cause or effect? • Expensive • No known treatment • Intensification of immunosuppression

Post-transplant anti-HLA Abs

o Uraemia o Hypoalbuminaemia o Hypocalcaemia o Hyperglycaemia o Metabolic acidosis o Abnormal LFTs

Potential biochemical features of acute pancreatitis

1. Recent contact with someone with acute diarrhoea and/or vomiting 2. Exposure to a known/potential source of enteric infection (e.g. consumption of unsafe food/water, animal contact) 3. Recent foreign travel 4. Factors that increase the risk of Clostridium difficile infection (CDI), e.g: • Recent (< 8 weeks) antibiotics • Recent (<8 weeks) hospitalization • Living in a care home • OCCUPATION: food-handlers, works in healthcare

Potential sources of infection in someone with gastroenteritis

• Pre-hepatic: too much bilirubin produced o Haemolytic anaemia o Gilbert's syndrome: enzyme deficiency o Unconjugated: bound to albumin, insoluble, not excreted = patient notices yellow eyes/ skin only

Pre-hepatic jaundice

≥41 and <48 mmol/mol = pre-diabetes

Prediabetic HbA1c

Infections: Cystic fibrosis Primary ciliary dyskinesia Kartagener syndrome Bronchial obstruction: tumour, foreign body Lupus, rheumatoid arthritis, inflammatory bowel disease, GVHD (graft versus host disease)

Predisposing conditions to bronchiectasis

o Wearing orthodontic appliances o Ill-fitting dentures o Sicca symptoms: dry mouth o Intraoral fungal infection o Poor oral hygiene o Age related anatomic changes of the mouth

Predisposing local factors of angular cheilitis

Age: 40-45 Dyspnoea: mild, late in disease Cough: early, in disease there is copious sputum (foul smelling) Infections: common Cor pulmonale: common Chest x-ray: prominent vessels, large heart Respiratory insufficiency: repeated Stereotype: Blue bloater

Predominant bronchitis features

Age: 50-75 Dyspnoea: severe, early Cough: late, scanty sputum Infections: rare Respiratory insufficiency: terminal Cor pulmonale: rare, terminal Chest x-ray: small heart, hyperinflated lungs Stereotype: pink puffer

Predominant emphysema features:

Reversal of warfarin anticoagulation

Prothrombin complex concentrate (factor IX complex) This contains a high concentration of factors vitamin K dependent factors like II, IX, VII and X

Clinical presentation of children with pneumonia

Presentation : Acute febrile illness, possibly preceded by typical viral URTI. Symptoms : Breathlessness ( Poor feeding) Irritability Sleeplessness Cough, chest or abdominal pain in older patients Audible wheezing is rare in LRTI, but can occur Young children rarely cough but may present with grunting tachypnoea and chest retractions

o Urinary frequency o Tenesmus: continuation or recurrent inclination to evacuate the bowels, caused by disorder of the rectum or illness (feeling of fullness in rectum)

Presentation of a pelvic abscess

o Pain in shoulder on affected side o persistent hiccup o intercostal tenderness o apparent hepatomegaly (liver displaced downwards) o ipsilateral lung collapse with pleural effusion

Presentation of a subphrenic abscess

• Nonspecific presentation • Sweating, anorexia, wasting • Swinging pyrexia: o fever (different to most infections), temperature going up and down, abscess get bigger and bigger and periodically release pus and then peak in temp • Localising features o Near bowel then diarrhoea o stomach: nausea o majority non-specific symptoms • Subphrenic abscess: o Pain in shoulder on affected side o persistent hiccup o intercostal tenderness o apparent hepatomegaly (liver displaced downwards) o ipsilateral lung collapse with pleural effusion • Pelvic abscess o Urinary frequency o Tenesmus: continuation or recurrent inclination to evacuate the bowels, caused by disorder of the rectum or illness (feeling of fullness in rectum)

Presentation of an intraperitoneal abscess

o Rapid onset (often few weeks) o Weight loss + osmotic symptoms + low energy o Abdominal pain o Often slim o Present as diabetes ketoacidosis (DKA)

Presentation of type 1 diabetes mellitus

1. older/obese o Often overweight o Symptoms present over a few months o Minimal weight loss (unless left for a long period) o Can present with complications like vision loss or foot ulcers or fungal infection o Can also present in a state of hyperosmolar hyperglycaemia state (HHS) or HONK

Presentation of type 2 diabetes

Cervical adenocarcinoma

Presentation/spread same as SCC (squamous cell carcinoma) Related to high risk HPV Precursor is Cervical Glandular Intraepithelial Neoplasia (CGIN) Treated same as CIN/SCC Stage for stage have worse prognosis than SCC: ? due to radioresistance

o Consequence of perforation of the anterior oesophageal wall o Occasionally through contiguous extension from retropharyngeal space infection o Consequence of prolonged tracheostomy o Clinical presentation: - Severe dyspnoea - Hoarseness can be first complaint - Swallowing may be difficult - Fluids may be regurgitated through the nose o Pretracheal space infection = serious because of impending airway obstruction and possible extension into mediastinum o Prompt surgical drainage is critical to prevent complaints

Pretracheal space infections

Pneumococcal vaccination (S. pneumoniae) give to: -Patients with chronic heart, lung and kidney disease -Patients with splenectomy -Infant vaccination schedule -May repeat after 5 years in certain populations -Influenza vaccination for vulnerable groups (annually) -2- 17 year olds -Over 65s -Chronic disease, multiple co- morbidities

Prevention of lower respiratory tract infections

o Originate from contiguous spread of a cervical spine infection (discitis/ vertebral osteomyelitis) o Local instrumentation of the trachea/ oesophagus o Or by haematogenous seeding

Prevertebral space infections

o Diagnosis: Anti-mitochondrial antibodies o IgM, raised alkaline phosphatase, o Bile duct granulomas at early stage o Then ductopenia and cirrhosis o Commoner in women o Biopsy not required for diagnosis, unless clinical uncertainty o Bile duct injury is characterised by granulomatous inflammation = destruction of bile ducts o Previously named primary biliary cirrhosis, but cirrhosis = end stage of disease

Primary biliary cholangitis

cortisol-secreting tumor of adrenal gland

Primary cushing's syndrome

excessive secretion of parathyroid hormone from one or more glands (PHPT)

Primary hyperparathyroidism

Decrease TSH, Increase T4

Primary hyperthyroidism

Causes of pleural inflammation

Primary inflammatory diseases - Collagen vascular diseases such as systemic lupus erythematosus and rheumatoid arthritis Infections - Usually secondary to pneumonias or pulmonary tuberculosis. Viral - primary Coxsackie B infection (Bornholm disease) Pulmonary infarction - Usually secondary to pulmonary arterial thromboembolus Emphysema - Secondary to ruptured bullae Neoplasms - Primary or secondary pleural neoplasms Therapeutic - Pleurodesis usually with talc to treat recurrent pleural effusions or recurrent pneumothoraxes. Iatrogenic - Radiotherapy to the thorax Immune reactions to a drugs

o Protein-calorie undernutrition (starvation) o Dietary deficiency of specific nutrients e.g. trace elements, water soluble vitamins/ fat soluble vitamins

Primary malnutrition

Vast majority are adenomas and benign May be derived from any hormone producing cell If functional, clinical effect secondary to hormone being produced Local effects due to pressure on optic chiasma or adjacent pituitary

Primary pituitary tumours

o Associated with ulcerative colitis, high alk phos o 'pruned tree' on biliary imaging o Periductal onion skin fibrosis o then ductopenia and cirrhosis o commoner in men o most patients have ulcerative colitis: 90% o 5% patients with UC will develop PSC o many patients have pANCA antibodies o diagnosis is imaging, showing a characteristic pruned tree on cholangiogram o liver biopsy shows chronic cholestatic changes: similar to long term obstructive jaundice and ductopenia: disappearing bile ducts, no longer a duct in every portal tract

Primary sclerosing cholangitis

o Detection of immune response to infection o Antibody detection IgM detection Seroconversion o Change from negative to positive result from one test to a subsequent test o Fourfold rise in titre - Rise in concentration of antibody from one test to a subsequent test - "Titre" is 1/greatest dilution at which antibody is detectable - i.e. if antibody is just detectable at a serum dilution of 1/64, the titre is 64 - "Fourfold rise in titre" would be e.g. 2 → 32 or 4 → 64 o Other immunological tests - IFN-γ release assays in tuberculosis

Principle of immunological tests

o Allergy to any vaccine component o Limited usefulness in immunocompromised o Delay in achieving protection

Problems with active immunisation

- Very broad spectrum, so predispose to C. difficile infection - Names do not end with -illin or start with cef- - So someone with a pencillin allergy may be missed

Problems with beta lactamase inhibitors

1. Inflamed mucosa 2. Low grade dysplasia 3. High grade dysplasia 4. Colorectal cancer • Inflamed mucosa -> colorectal cancer • Low grade dysplasia -> colorectal cancer • BSG guidelines 2010 : depending on risk factors that they have

Process of development of colorectal cancer in ulcerative colitis

Superficial fungal infections which affect the skin, hair, nails and musculocutaneous tissue This is caused by: Dermatophytes Malassezia Candida

What is superficial infection caused by and what does it affect?

• Scarring gradually incs and starts to link vascular structures (bridging) eventually transforming the liver tissue into separate nodules = end stage = cirrhosis • Chronic liver disease: remodelling = bands of fibrosis that bridge between portal tracts and hepatic veins • This progression happens in all causes of chronic liver disease, rate of progression = variable (few months to decades) • Remodelling becomes complete, and hepatocytes form nodules surrounded by fibrous tissue • Portal blood entering the liver can flow through vessels in the fibrous tissue and not percolate through sinusoids • The cirrhotic liver therefore is inefficient in metabolic function, even though it is normal size or larger

Progression of chronic liver disease

o Effects on micro-organisms - Antimicrobial spectrum, sporicidality o Chemical properties - Shelf life, in-use concentration, compatibility with other chemicals o Physical effects - Corrosiveness o Harmful effects - Irritant potential, toxicity

Properties to consider of a disinfectant

Candida Aspergillus

What is systemic fungal infection caused by?

allows you to assess risk of osteoporotic fracture

What is the FRAX calculation tool?

Gram positive bacillus Assocaciated with acne Can also cause device associated and post procedural infections

Propionibacterium acnes

Azatanavir Darunavir Ritonavir-->used to boost levels of other protease inhibitors

Protease inhibitors for HIV

Paritaprevir Grazoprevir

Protease inhibitors for Hep C

Advanced glycosylated end products This is a non-enzymatic process and the rate of formation is proportional to: Glucose formation Time May explain long term complications of diabetes Scientific basis of commonly used tests

Protein + glucose=

o Fungi are eukaryotes so share the same mechanisms of protein synthesis with humans o Probably for this reason protein synthesis is not a target for antifungal agents

Protein synthesis in fungi

o Multi-resistant gram negative bacillus o Opportunistic pathogen o Can cause respiratory infections, UTIs, soft-tissue and other infections in vulnerable patients o Often produces characteristic green pigment

Pseudimonas aeruginosa

Mobile mass (of Aspergillus) within a pre-exisiting lung cavity Old cavities left by previous TB or sarcoidosis become colonised with Aspergillus spp. Symptoms include: cough, haemoptysis, weight loss, wheeze & clubbing. Some are asymptomatic. Can be demonstrated on either chest X-ray or CT thorax. The diagnosis can be confirmed by a positive test for Aspergillus IgG antibody Sputum culture may be positive for Aspergillus spp. Complication: Massive haemoptysis Treatment: 10% cases resolve spontaneously, surgical resection, antifungals (injected into the cavity, or orally for symptom relief).

Pulmonary aspergilloma

disease caused by the presence of Mycobacterium tuberculosis in the lungs; characterized by the formation of tubercles, inflammation, and necrotizing caseous lesions Requires exposure then reactivation at a later stage to cause pulmonary symptoms

Pulmonary tuberculosis

o Rifampicin: - RNA polymerase inhibitor - Prevents synthesis of mRNA o Cornerstone of anti-tuberculous chemotherapy

RNA synthesis inhibitors

Viral pathogens that cause pneumonia in neonates

RSV Herpes simplex CMV Adenovirus

Viral pathogens which cause pneumonia in 1-3 month olds

RSV Others (not viruses) like C.trochomatis

Sex cord stromal tumours

Rare; arise from ovarian stroma, which was derived from sex cord of embryonic gonad Can generate cells from the opposite sex; Thecoma/ fibrothecoma/ fibroma Benign, thecomas and fibrothecomas produce E2 (oestrogen) (also rarely androgens), fibromas hormonally inactive Comprised of spindle cells (plump spindle cells with lipid droplets = thecoma appearance) Meig's syndrome = ovarian tumour, right sided hydrothorax, ascites Granulosa cell tumours Low grade malignant, produces E2 Sertoli-Leydig cell tumours Produce androgens; 10-25% malignant

o To provide adequately broad spectrum o Single agent may not cover all required organisms - Polymicrobial infection (multiple bacteria or bacteria + fungi) - Empiric treatment of sepsis o To increase efficacy - Synergistic combination may improve outcome - β-lactam/aminoglycoside in streptococcal endocarditis - Cell wall agent/protein inhibitor in severe Group A streptococcal infection o To reduce resistance - Organism would need to develop resistance to multiple agents simultaneously - Antituberculous chemotherapy

Reasons for combining antimicrobial therapy

Targeted/tailored therapy Based on tumour genomics eg EGFR mutations, ALK re-arrangements Immune checkpoint inhibitors eg PD-L1

Recent advances in treatment of lung cancer with advanced disease

Why is it important to recognise dysplasia?

Recognition of dysplasia gives us a chance to treat a potentially fatal tumour before it arises; the abnormal cells have not yet acquired the capacity for invasion so they cannot spread. Elimination of the abnormal cells removes the basis on which cancer will develop. This is the whole basis of the cervical screening programme.

Components of whole blood

Red blood cells Platelets Plasma-->fresh frozen plasma, cryoprecipitate, fractionation containing factor concentrates like FVIII, FIX, prothrombin complex, albumin, immunoglobulin

• Systolic blood pressure <90mmHg or MAP < 65mmHg • Lactate > 2 mmol/L • Heart Rate >130 per minute • Respiratory Rate >25/min • Oxygen Saturation <91% • Responds only to Voice or Pain or unresponsive • Purpuric rash • NEWS >7 • Start BUFALO

Red flag symptoms of vital signs

• Commonest form of oesophagitis • Caused by reflux of gastric acid = gastro-oesophageal reflux • And or bile (duodeno-gastric reflux

Reflux oesophagitis

• Inflammatory cells, loose distinction between basal and lamina propria, the basal cells look like the populate a greater amount of the oesophageal lining • Squamous epithelium o Basal cell hyperplasia o Elongation of papillae (go higher up, they contain blood vessels) o Including cell desquamation o Inflammation • Lamina propria o Inflammatory cell infiltration: neutrophils, eosinophils, lymphocytes • Looks red and inflamed • Many inflammatory cells that have come through the lining, erosion and left with granulation tissue

Reflux oesophagitis histology

• 4 anatomic regions o cardia - area around the GO junction o fundus - located in the upper part of the body of the stomach o body - main part of the stomach o antrum - near the pylorus • 3 histological regions with different functions: o cardia o body o antrum

Regions of the stomach

Cervical intraepithelial neoplasia III

Regression 33% Persistence ~56% Progression to invasion 20% - 70%

Cervical intraepithlial neoplasia II

Regression 40% Persistence 40 % Progression to CIN III 20% Progression to invasion 5%

Cervical intraepithelial neoplasia 1

Regression 60% Persistence 30 % Progression to CIN III 10% Progression to invasion 1%

• PTH • Vitamin D • FGF23 o Secreted by osteocytes in response to an increase in the active form of vitamin D o Suppresses 1α hydroxylation of vitamin D by the kidneys (negative feedback) i.e. prevents the activation of vitamin D o Increases renal phosphate excretion • Calcitonin o Secreted by the C-cells of the thyroid gland in response to increased calcium concentration o Opposes the effect of PTH by acting on osteoclasts to inhibit bone resorption i.e. inhibit bone breakdown to release calcium and other minerals o Function is usually insignificant in the regulation of normal calcium homeostasis • Oestrogen-->as oestrogen levels drop, more prone to bone disease i.e. after menopause

Regulators of calcium and phosphate homeostasis

Candida from the blood lodges in the kidney tissue during filtration This occurs in immunocompormised preamture nenonates Results in: Fever Abdominal pain Oliguria-->low output of urine Anuria-->non-passage of urine

Renal candidosis

Have to constantly check they are not forming new antibodies

Renal transplant pathway

• Pooled human immunoglobulin (IV or SC) o Used in Rx of antibody deficiency states • G-CSF/GM-CSF o Act on bone marrow to increase production of mature neutrophils • IL-2 (Stimulates T cell activation- rarely used) • α-interferon (Main use in treatment of Hep C) • β-interferon (Used in therapy of MS) • γ-interferon o Can be useful in treatment of certain intracellular infections (atypical mycobacteria), also used in chronic granulomatous disease and IL-12 def

Replacement therapies and immune stimulation

- Fundamental property of the bacterium/antibiotic combination - Usually relates to permeability/entry of the antibiotic into the cell - Gram negatives - glycopeptides, daptomycin - Gram positives - aztreonam, colistin - Anaerobes - aminoglycosides - Streptococci - aminoglycosides

Resistance mechanisms are either innate or acquired. Describe innate resistance mechanisms

Disulfiram reaction with alcohol, vestibular dysfunction, METALLIC TASTE.

side effects of metronidazole

Viruses that cause bronchiolitis

Respiratory Syncytial Virus (RSV) Metapneumovirus Adenovirus Para-influenza virus Influenza Rhinovirus

-different pathogens characteristically colonize the respiratory tract at different levels -the upper and lower respiratory tracts offer different environments and favor different microbes Influenza Pneumonia Pulmonary TB Atypical infections in the immuno compromised

Respiratory infections

Common symptoms reported in early children years

Respiratory mainly e.g. cough Fever Gastroenteritis Earache Rash

A highly contagious virus that causes an infection of the upper and lower respiratory system. o Disease names RSV o Epidemiology: - Worldwide distribution, occurs in epidemics in winter - Commonest in young children, 70% are infected and 30% have clinical illness in their first year of life o Mode of transmission: - Aerosolization of respiratory secretions o Important clinical syndromes: - Bronchiolitis: affects children under 2 years - Inflammation of the smallest airways—bronchioles - Causes cough, wheeze, hypoxia and apnoeas • HIV—Human immunodeficiency virus o Epidemiology: - 26.9 million living globally with HIV - Of those, 70% live in Sub -Saharan Africa o Mode of transmission: - Virus is present in blood, genital secretions, breast milk - Transmitted vertically, sexually, needlestick o Clinical course: - HIV targets helper T lymphocytes (CD4) cells, part of the cell-mediated immune system*** - 2-6 weeks after transmission, patients may develop an acute seroconversion illness - Fever, sore throat, lymphadenopathy ("Flu-like") - Asymptomatic chronic infection follows: - steady state between virus and immune system, lasts 5-15 years*** - AIDS = rise in viral load and fall in CD4 count, patient becomes vulnerable to opportunistic infections - AIDS defining illnesses: e.g. tuberculosis, pneumocystis pneumonia, cryptococcal meningitis, cerebral toxoplasmosis, Kaposi's sarcoma • IMPORTANT: many viruses can induce hepatitis as part of a wider clinical syndrome

Respiratory syncytial virus

o Infects humans and animals, can spread between species o Peaks in winter annually o Virology - 3 distinct types: influenza A, influenza B, influenza C - Influenza A mutates regularly, so strains vary yearly - 2 important surface proteins H & N have multiple variants - Used in nomenclature: e.g. H1N1 (swine), H3N2 (seasonal)*** o Mode of transmission: - Aerosolised respiratory secretions (coughs and sneezes!) o Important clinical syndromes: 1. Primary influenza illness: fever, myalgia (muscle aches), then headache, cough, sore throat, nasal discharge 2. Post-influenza secondary bacterial lung infection: with S.pneumoniae, H.influenzae, S.aureus

Respiratory viruses--INFLUENZA

o Retropharyngeal abscesses are among the most serious of deep space infections o Infection can extend directly into anterior or posterior regions of the superior mediastinum or entire length of posterior mediastinum via the danger space o Can occur in both adults and children o Infection can come from local or distant sites o Penetrating trauma e.g. from chicken bones or instrumentation = usual source of spread - Sore throat or difficulty in swallowing/ breathing = first indication o Distant sources of infection: odontogenic sepsis o Peritonsillar abscess: rare cause o Infection from these sources may often obscure diagnosis because of associated trismus (lock jaw, i.e. reduced opening of the jaw) = examination of posterior pharyngeal wall difficult o Acute necrotising mediastinitis is the most feared complication o Infection in the danger space between the alar and prevertebral fasciae may drain by gravity into the posterior mediastinum = mediastinitis and empyema o Introduction of Abs: mediastinal extension = uncommon o Most cases of acute mediastinitis come from oesophageal perforation

Retropharyngeal and danger space infections

MALARIA (unless proven otherwise)

Returning traveller + fever =

o Defective lower oesophageal sphincter - Does not prevent gastric acid/contents coming up o Hiatus hernia o Increased intra-abdominal pressure - Tumour in abdomen or ascites o Increased gastric fluid volume due to gastric outflow stenosis - Volume in stomach e.g. distal gastric tumour can back up and flow into oesophagus

Risk factors of reflux oesophagitis

amoxicillin/clavulanate and clarithromycin

treatment for community acquired pneumonia

Aka the common cold-->respiratory virus Rhino=nose Epidemiology: Worldwide distribution Occurs in epidemics in the autumn, winter and spring Mode of transmission: Aerosolised respiratory secretions from the nose and eyes Important clinical symptoms: Common cold--sneezing, nasal obstruction and discharge, sore throat, cough, headache and fever

Rhinovirus

Rhinovirus is the agent responsible for most common colds Can cause a lower respiratory tract infection, can exacerbate asthma Tests: : PCR on NPA/throat swab Treatment: supportive

Rhinovirus tests and treatment

• Diet o Dietary fibre: high fibre = protective o fat, red meat, calcium inc = inc risk o folate = protective • Obesity/ physical activity • Alcohol • NSAIDS and aspirin = protective, decrease the risk • Hormone Replacement Therapy and oral contraceptive • Schistosomiasis • Pelvic radiation: radiotherapy • Ulcerative colitis and Crohn's disease

Risk factors for colorectal cancer

BMI above 30 Previous macrosomic baby-->baby that is significantly larger than average i.e. above 4.5kg Previous gestational diabetes Family history Ethnic minority

Risk factors for gestational diabetes

swimming (or other water exposure), trauma (e.g. ear scratching, cotton swabs), occlusive ear devices (e.g. hearing aids, ear phones), allergic contact dermatitis (e.g. due to shampoos, cosmetics), and dermatologic conditions (e.g. psoriasis).

Risk factors for otitis externa

Family history (genetic susceptibility) Affected father gives a 3-8% risk Affected mother gives a 2% risk Both parents affected gives a 30% risk

Risk factors for type 1 diabetes mellitus

Same as reflux i.e. Defective lower oesophageal sphincter - Does not prevent gastric acid/contents coming up o Hiatus hernia o Increased intra-abdominal pressure - Tumour in abdomen or ascites o Increased gastric fluid volume due to gastric outflow stenosis - Volume in stomach e.g. distal gastric tumour can back up and flow into oesophagus Being male Caucasian Overweight

Risk factors of Barrett's oesophagus

o Early age of onset o Duration of disease > 8-10 years o Total or extensive colitis beyond splenic flexure o PSC: primary sclerosing cholangitis: narrowing in the bile duct o Family History of CRC o Severity of inflammation: pseudopolyps o Presence of dysplasia

Risk factors of colorectal cancer when you have UC

Female Middle aged Overweight

Risk factors of gallstones

4-6 weeks of IV antibiotics depending on the bug

treatment for infective endocarditis

• Risk of ulcerative colitis in 1st degree relative: 8 times • Risk of Crohn's disease in 1st degree relative if someone in the family has UC = 1.7 x • Risk of Crohn's disease in 1st degree relative 10 x • Risk of UC in 1st degree relative if someone in the family has Crohn's disease = 3.8 x

Risk of developing Crohn's or UC if family have it

anti-CD20 • Chimeric mAb against CD20- B cell surface • First approved in '97 for treatment of chemotherapy resistant DLCL • Many uses: o Lymphomas, leukaemias o Transplant rejection o Autoimmune disorders

Rituximab

Making diagnosis-by examing the biopsy Staging the tumour and also play a role in predicting prognosis Help guide treatment

Role of a pathologist in lung cancer

• Disease confirmation. • To identify relatives and patients at risk of developing autoimmune diabetes. • Negative predictive value of ICA and IAA is almost 99%. • Increased risk of disease development with greater number of different autoantibodies present and younger age of patient

Role of autoanitbodies in diagnosis of type 1 diabetes mellitus

Multiple cytokine release: Innate inflammatory Response Drive for immunoglobulin production

Role of the Th2 T cell

Alkaline phosphatase Alanine aminotransferase Bilirubin Albumin Total protein GGT: gamma glutamyl transferase

Routine LFTs consist of:

o Epidemiology: - Previously common in UK with 6-8 yearly epidemics - Now due to vaccine, rare o Mode of transmission: - Droplet transmission from respiratory route o Important clinical syndromes: 1. Primary rubella o Mild illness, fever and maculopapular rash o Arthralgia (joint pain)/ arthritis (joint inflammation) occurs in 30% adults*** 2. Congenital rubella o Classic triad***: o Bilateral cataracts, sensorineural deafness, microcephaly o Risk of foetal malformation is highest in first 12 weeks of pregnancy •

Rubella aka german measles

Causes of a closed pneumothorax

Ruptured emphysematous bullae - as in picture left Common inflammatory lung diseases Asthma, pneumonia, tuberculosis, cystic fibrosis Traumatic - lung tears from fractured ribs Iatrogenic Mechanical ventilation at high pressures Lung and pleural biopsy procedures Some rare cystic lung diseases - Langerhans' cell histiocytosis, lymphangioleiomyomatosis Catamenial due to pleural endometriosis

prescription

Rx

Bacterial pathogens which can cause pneumonia in 1-3 month olds

S. pneumoniae H. influenzae type B

o Heat stable enterotoxin o Nausea and vomiting (often projectile) o No fever o Little or no diarrhoea o Often 1-4hrs after ingestions o Associated with mayonnaise, meat, dairy products

S.aureus

Bacterial pathogen which causes penumonia in 5 years and older

S.pneumoniae

Bacterial pathogens which cause pneumonia in 4 month to 5 year olds

S.pneumoniae H.influezae type b

autosomal recessive cause of hereditary pancreatitis

SPINK1 gene

chronic inflammatory disease in which small nodules (granulomas) develop in lungs, lymph nodes, and other organs Non-caseating perilymphatic pulmonary granulomas, then fibrosis Hilar nodes usually involved Other organs may be affected- skin, heart, brain Hypercalcaemia & elevated serum ACE Typically young adult females, aetiology unknown

Sarcoidosis

hypocalcaemia

what are the symptoms of hyperphosphataemia usually caused by?

Damage to the epidermis AND dermis Epidermis is gone and there is disruption in the dermis Still painful as there are still some of the pain receptors in the dermis

Second degree burn

• Neutrophils very important after initial breach of innate defences • Less number = increasing risk of infection • Qualitative defects (e.g. lose ability to kill or chemotaxis): rare, need consultant immunologist • Quantitative defects (less present): more GP treated

Second line of defence: neutrophils

Non-neoplastic increase in parathyroid parenchymal cell mass within all parathyroid tissue with a known stimulus. Common in patients with renal failure and on dialysis. Identical pathologic features to primary hyperplasia. May be associated with massive gland enlargement.

Secondary and tertiary hyperparathyroidism

usually occurs due to drugs like immunosuppresants

Secondary antibody deficiency

• Breakdown in physical barriers: e.g. Cystic fibrosis (mutation affecting the secretions in the lungs = recurrent pneumonia • Protein loss o Burns, protein losing enteropathy (protein lost through the gut), malnutrition (no albumin so cannot make antibodies to get rid of disease) • Malignancy o Especially lymphoproliferative disease, myeloma (clonal cells e.g. B cells no room for the other part of the immune system to develop, fill the bone marrow as proliferative) • Drugs: o Steroids o DMARDS (disease modifying anti-rheumatic drugs e.g. methotrexate) o Rituximab o anti-convusltants o myelosuppressive (suppressing the bone marrow) • Infection: HIV, TB

Secondary causes of immunodeficiency

issue is with the pituitary gland overproducing ACTH which causes the adrenal gland to produce cortisol

Secondary cushing's disease

Hyperplasia of all 4 parathyroid gland: compensation for hypocalcemia in vhronic kidney disease Decreased Ca, increased PTH Could be due to malabsorption of Ca and vitamin D deficiency

Secondary hyperparathyroidism

Very common, more common than primary tumours Usually present as multiple discrete nodules, can also be solitary Most common are carcinomas from various sites eg. Breast, GI tract, Kidney

Secondary lung tumours

Secondary pleural neoplasms

Secondary malignant are either: Carcinomas of e.g. the breast, lung or others which are common Others e.g. lymphoma, melanoma

precipitated by a disease state, surgical procedure, or medication o Nutrients present in adequate amounts but appetite is suppressed o Nutrients present in adequate amounts but absorption and utilisation are inadequate o Inc demand for specific nutrients to meet physiological needs

Secondary malnutrition

Majority of liver tumours are secondary (metastases) Commonest sites of origin are: - Lung - Breast - Colon - Pancreas Multiple whitish nodules May replace large volumes of the liver before liver function is compromised

Secondary tumours of the liver

how is sarcoidosis first diagnosed?

Seen in young women First diagnosed by a hilar lymphadenopathy on a chest x-ray

C.diff when treated with broad spectrum antibiotics

what can cause colitis secondary to treatment?

Describe a haematopoietic stem cell

Self renewal High proliferative potential Differentiation potential for all lineages Long term activity throughout the lifespan of the individual This has been demonstrated by experimental proof of stem cells transplanted from one mouse to another over several generations and bone marrow transplantation in humans

Characterises the performance of a test This is to independently confirm the results

Sensitive vs specific

o To inform decisions on targeted antimicrobial therapy o Initial treatment is with "empiric" therapy o Subsequent treatment is "targeted" Requires: o Isolation of micro-organism o Antimicrobial susceptibility testing o The correlation between antimicrobial sensitivity and clinical response is not absolute

Sensitivity testing, uses and limitations

Measure of how good the test is in identifying people WITH the disease

Sensitvity

Requires viable microorganisms➡bacteria or fungi This principle is about putting a culture of the microorganism in the presence of antimicrobial agent Work out if the concentration of antimicorbial in the body is high enough to kill the microorganism Solid or liquid media

Sensitvity testing principle

toxic inflammatory condition arising from the spread of microbes, especially bacteria or their toxins, from a focus of infection SIRS (systemic inflammatory response syndrome) and focus of infection

Sepsis

Pathological fluids in the pleural cavities

Serous fluid - pleural effusion Pus - empyema or pyothorax-->Usually secondary to pneumonia Blood - haemothorax-->Usually traumatic or a ruptured thoracic aortic aneurysm Bile - chylothorax -->Usually traumatic Air-pneumothorax

Defective cell-mediated and humoral immunity i.e. no adaptive immune response Diagnosis-->No T cells and a suggestive history Rx: Paediatric emergency Antibiotics, antivirals, antifungals Asepsis-->sterile Haemopoietic stem cell transplant (only cure) Screen for SCID in America

Severe Combined Immunodeficiency (SCID)

Acute haemolytic reaction due to incompatibility: onset, signs and symptoms

Severe reactions may occur early in the transfusion, within the first 15 minutes Milder reactions may occur later but usually before the end of transfusion Fatal 20-30% Confirm by repeating the cross matching Signs and symptoms: Fever and chills Back pain Infusion pain Hypotension /shock Hemoglobinuria->excretion of excess Hb in the urine (may be the first sign in anesthetized patients) Increased bleeding (DIC) Chest pain Sense of "impending death"

Transfusion of bacterial contaminated components signs and symptoms

Severe reactions may occur early in the transfusion, within the first 15 minutes Blood components might be contaminated by bacteria from the donor's skin during collection or contamination from the environment Rigors High fever Severe chills Hypotension Nausea Vomiting Dyspnoea Circulatory collapse This may occur in 1 in 500, 000 transfusions 35% mortality of bacteria in transfusions This is confirmed as blood cultures from the patient are positive and cultures from the blood bag are positive for the same bacteria

A condition in which the circulatory system fails to provide sufficient circulation to enable every body part to perform its function; also called hypoperfusion. • Interruption to the supply of substrates to the cell o Oxygen, glucose, water, lipids, amino acids, micronutrients • Interruption to the removal of metabolites from the cell o Carbon dioxide, water, free radicals, toxic metabolites

Shock

Short term: Macrosomia of baby Pre-eclampsia Stillbirth Neonatal morbidity Long term: Obese child Mother will be more likely to develop type 2 diabetes later

Short term and long term consequences of gestational diabetes

• No benefit giving them prophylaxis, before they get infection have to wait for them to get it • Inflammatory condition = pancreatitis not an infection, can become infected then treat with Abs • Secondary infection of pancreatic or extrapancreatic necrosis occurs in approximately one-third of patients with necrotizing pancreatitis • In the first week after admission, there is no role for routine antibiotic prophylaxis in the treatment of necrotizing pancreatitis • Antibiotics should be withheld until infection is proven with positive cultures • In most patients, infection of pancreatic or extrapancreatic necrosis does not occur until week 3 or 4

Should pancreatitis be treated with prophylactic antibiotics?

state of adaptation or dysregulation of thyrotropic feedback control wherein the levels of T3 and/or T4 are abnormal, but the thyroid gland does not appear to be dysfunctional. This condition is often seen in starvation, critical illness, or patients in the intensive care unit. Treatment is directed at treating the underlying illness

Sick euthyroid disease

• Carbohydrate and lipid metabolism o Diabetes o Hyperlipidaemia • Reduced protein synthesis = Poor wound healing • Osteoporosis • Glaucoma and cataracts • Psychiatric complications

Side effects of immunosupressive drugs

When do we transfuse red blood cells?

Significant bleeding Acute anaemia Chronic anaemia

o Hypertension o Moon face o Truncal obesity o Buffalo hump o Weak muscles o Osteoporosis o Insomnia o Excess sweating o Mood swings o Headaches o Chronic fatigue o Women may have increased hair growth (hirsutism) o Irregular menstruation

Signs and symptoms of Cushing's

• Tetany o Latent tetany may be demonstrated by Chvostek's sign (tapping over the facial nerve causes twitching of facial muscles) or Trousseau's sign (compression of the forearm produces spasms of the wrist and hand) • Paraesthesia in the extremeties • Cramps • Convulsions • Psychosis

Signs and symptoms of hypocalcaemia

• Can affect various systems: • CNS - neuromuscular hyperexcitability (tremor, tetany, convulsions), muscle weakness, depression, psychosis • Cardiovascular - ECG changes, reduced contractility, arrythmia • GI - nausea and anorexia • Biochemical consequences: hypokalaemia, hypocalcaemia, with associated signs and symptoms

Signs and symptoms of magnesium depletion

• Neonatal jaundice: read the guidelines and phototherapy • Jaundice: sometimes hard to see in darker colour skins • Finger clubbing: lack of nutrients to the nail bed • Spider naevi • Gynaecomastia: binding proteins affected and therefore breast tissue caused • There may be no physical signs: hepatitis

Signs of liver disease

non-blanching rash systemically unwell low blood pressure tachycardia

Signs of meningococcal septicaemia

Tachypnoea Tachycardia Hypotension

Signs of pneumonia

fibrotic lung disease from inhaling silica particles Silica - sand & stone dust Kills phagocytosing macrophages Fibrosis & fibrous silicotic nodules, also in nodes Possible reactivation of tuberculosis Increased risk of lung carcinoma - lung carcinoma with silicosis is a UK "prescribed occupational disease" Mixed dust pneumoconiosis - silica with other dusts

Sillicosis

a life cycle that must make use of an intermediate host

Simple indirect life cycle

if the recommended dose has an acceptable toxicity profile

Simulations can be used to determine what dose of antibiotic will achieve a high probability of target attainment; what needs to be confirmed to see if the antibiotic can be used to treat patients?

mTOR inhibitor (a growth factor); binds FKBP. Blocks T-cell activation and B-cell differentiation by preventing response to IL-2. Used in kidney transplant (the kidney survives). Tox: anemia, thrombocytopenia, leukopenia. Insulin resistance, hyperlipidemia. synergistic with cyclosporine, also used in drug elduing stents • Macrolide antibiotic o Also binds to FKBP12 like calcineurin inhibitors but different effects o Inhibits mammalian target of rapamycin (mTOR) • Mode of action o Inhibits response to IL-2 • T cell effects o Cell cycle arrest at G1-S phase • The prototype macrolide, which was derived from Streptomyces hygroscopicus isolated on Easter island, sirolimus35 (Rapamune; Wyeth Research) is structurally related to tacrolimus but is ineffective against calcineurin.

Sirolimus (rapamycin)

o Amino acids o Beta adrenergic stimulation o Fasting, hypoglycaemia o Exercise o Gastrin, CCK, cortisol

Stimuli for glucagon to be released

a = arrector pilli muscle b = hair follicle c = sebaceous gland • Lots and lots of hairs • Epidermis thin • No basket weaved keratin on • Dermis quite thin, subcutaneous fat and some muscle

Skin of the scalp

• No hair follicles • Epidermis thicker • Dermis thicker • Subcutaneous and muscle quite thick too

Skin of the sole of the foot

Sensory organs for touch, pressure, pain, cold, and warmth Meissner corpuscles Merkel cells Pacinian corpuscles Ruffini endings

Skin receptors

Less cytoplasm Nuclear chromatin fine Less prominent/no nucleoli

Small cell carcinoma

cytokines

Small protein molecules such as interferon and interleukin which are secreted by certain cells of the immune system that can result in inflammation?

o Glucose o Fatty acids and ketones o Vagal nerve stimulation o Gut hormones o Drugs (diabetes medication) o Prostaglandins

Stimuli for insulin release

o Sympathetic stimulation o Alpha adrenergic agents (adrenaline) o Beta blockers o Dopamine o Serotonin o Somatostatin

Stimuli which causes insulin release to be inhibited

inhibiton of PTH secretion

what can increased calcitrol lead to?

Measure of how goof the test is at correctly defining people WITHOUT the disease

Specificity

Trepenoma pallidum is an example and can cause syphilis There are other species of spirochaetes which cause imporatnt infections: Leptospirosis Lyme disease

Spirochaetes (Bacteria)

Hep C because it is an RNA virus

what chronic virus infection is the exception to the conditions and why?

removal of the spleen • Spleen - source of complement and antibody producing B-cells, removes opsonised bacteria from blood. • Causes - traumatic, surgical (stomach removed, spleen can be mixed) or functional e.g. sickle cell anaemia o Epstein barr virus: rugby get damage and then have to have removed as spleen damaged from virus before • Streptococcus pneumoniae, Haemophilus influenzae type B, N. meningitidis, malaria • High mortality, vaccination, prophylactic penicillin, education - seek help if unwell • Parasite: plasmodium falciparum: antimalarial tablets

Splenectomy

• Mostly occurs in people with liver cirrhosis • Spontaneous bacterial peritonitis (SBP) is defined as an ascitic fluid infection without an evident intra-abdominal surgically treatable source • Diagnosis is based on a positive ascitic fluid bacterial culture and an elevated ascitic fluid absolute polymorphonuclear leukocyte (PMN) count (≥250 cells/mm3) o Should be clear usually, milky appearance then can see infection • Aetiology o Bacteria within the gut lumen cross the intestinal wall into mesenteric lymph nodes (translocation, a normal process) o Lymphatics carrying the contaminated lymph ruptures because of the high flow and high pressure associated with portal hypertension. Seeding of ascitic fluid via the blood also occurs • The vast majority of patients with SBP have advanced cirrhosis with ascities • Treatment is based upon antibiotics • Antibiotic prophylaxis may be given • Surgically treatable infections, e.g. perforated duodenal ulcer, that lead to ascitic fluid infection are called secondary bacterial peritonitis • Guidelines suggest that antibiotic prophylaxis for SPB be given to the following patients: o Patients with cirrhosis and gastrointestinal bleeding. Antibiotic prophylaxis in this setting has been shown to decrease mortality in randomized trials. o Patients who have had one or more episodes of SBP. In such patients, recurrence rates of SBP within one year have been reported to be close to 70 percent. o Patients with cirrhosis and ascites if the ascitic fluid protein is <1.5 g/dL (15 g/L) along with either impaired renal function or liver failure. Impaired renal function is defined as a creatinine ≥1.2 mg/dL (106 micromol/L), a blood urea nitrogen level ≥25 mg/dL (8.9 mmol/L), or a serum sodium ≤130 mEq/L (130 mmol/L]). Liver failure is defined as a Child-Pugh score ≥9 and a bilirubin ≥3 mg/dL (51 micromol/L).

Spontaneous bacterial peritonitis

Define endometriosis

Spread of endometrium into the pelvis

A demarcation line, the squamocolumnar (SC) junction or "Z-line", represents the normal esophagogastric junction where the squamous mucosa of the esophagus and columnar mucosa of the stomach meet • Normal squamous on left, then lots of goblet cells that you see in the intestine instead of the stomach = example of intestinal metaplasia

Squamo-columnar junction

Transformation zone

Squamocolumnar junction (most common area for cervical cancer) Physiological area of squamous metaplasia Between exocervix and endocervix The transformation zone is vulnerable to oncogenic effects of HP which is the site of development of cervical intraepithelial neuplasia (CIN)

• Wide geographical variation in incidence o High in Iran, China, S Africa, S Brazil • Risk factors o Tobacco and alcohol o Nutrition: potential sources of nitrosamines o Thermal injury: hot beverages (hot tea without milk) o Human papilloma virus (HPV) o Male o Ethnicity: black • Location: middle and lower third <15% in upper third of oesophagus • A high grade squamous dysplasia is confined to the basement membrane • An invasive squamous cell carcinoma is not confined to the basement membrane • Squamous carcinoma preceded by squamous dysplasia • Dysplastic progression • Break through basal layer into lamina propria and becomes invasive

Squamous carcinoma

TUMOUR NODE METASTASES

Staging of oesophageal cancer

• Dukes stage • TNM stage: Tumour nodes metastasis (most commonly used) o T staging does local spread • May be clinical (imaging) or pathological • Describes extent of local and distant tumour spread

Staging: determinants of prognosis

Heat stable enterotoxin onset is often 1-4 hours after ingestion Causes: Nausea and vomiting (often projectile) No fever Little or no diarrhoea Associated with mayonnaise, meat, dairy products

Staphylococcus aureus

Impetigo is caused by

Staphylococcus aureus or Streptococcus pyogenes

Haempoiesis

Stem cells give rise to sufficient numbers of committed haemopoietic progenitors to maintain the cellular content of the blood throughout the life span of the individual. Mature blood cells have a finite life - e.g. an erythrocyte (red blood cell) has a life span of about 120 days while a neutrophil (a type of white blood cell) lasts only 6-10 hours in the bloodstream.

o Heat-->moist (autoclave which is the delivery of steam under high pressure), dry (controlled temperature cycles) o Chemical-->gas, liquid o Filtration o Ionising radiation-->used for single use disposable equipment

Sterilisation methods

o Glucose o Somatostatin o Free fatty acids o Ketones o Insulin

Stimulation for inhibition of glucagon release

How is cryoprecipiate stored?

Storage: -30oC Shelf life: 3 years (frozen) Volume per unit: 15ml Maximum transfusion time: stat

How are platelets stored?

Stored at "room temperature" (22oC) on an agitator Shelf-life 5 days from collection Volume: 250-350 ml Usual transfusion time: 30 mins/unit

how is fresh frozen plasma stored?

Stored at -300C for up to 36 months Volume of 1 unit: 300ml Usual transfusion time: 30 mins/unit Thawed immediately before use (takes 20-30 mins) 6 hours after thawing, the levels of the labile factors, V and VIII begin to diminish

How is 1 unit of red blood cells stored?

Stored at 4oC for up to 35 days from collection Volume of unit: 280 +/- 60ml Therapeutic dose: 10-20ml/kg recipient Usual transfusion time: 1.30 -3 hrs 4 h limit from removal from cold storage to end of transfusion

Selective protection of the vulnerable Elimination--herd immunity Eradication

Strategic aim of vaccinations

o Select a more appropriate normal population o Use a combination of tests e.g. LFT profiles o Combine tests to achieve a diagnostic goal e.g. neonatal screening for PKU and hypothyroidism Do a sensitive first line test (low cost) Then perform a specific test for screen positives (higher cost)

Strategies to improve tests

o 3 closely related species of pus forming streptococci o Associated with abscesses: dental, lung, liver, brain and others

Streptococci milleri complex

Group B strep Commonest cause of bacterial meningitis and sepsis in neonates (babies aged under 3 months)

Streptococcus agalctiae

Gram-positive cocci, aerobe o Formerly known as Streptococcus bovis o A type of α- haemolytic streptococcus that forms part of bowel flora o Bacteraemia with this organism can be associated with colonic malignancies

Streptococcus gallolyticus

Causative organisms of meningitis in those from 1 month to 5 years

Streptococcus oneumoniae Neisseria meninigtidis

Gluten free diet-->provides symptomatic improvement for most patients Reduces risk of long-term complications including anemia, female infertility, osteoporosis and cancer

Treatment of coeliac disease

• Structural changes, fibrosis o Portal hypertension o Increased blood flow, stiff liver o Pressure rises in portal vein o Oesophageal varices: bleeding, can cause haemorrhage • Liver cell failure o fewer hepatocytes +/- blood bypasses sinusoids o Synthetic: oedema, bruising, muscle wasting o Detoxifying: drugs, hormones, encephalopathy, o Ascites: low albumin, portal hypertension, hormone fluid retention (aldosterone) o Inefficient liver cell function due to shunting of blood and fewer hepatocytes = liver cell failure • Excretion o Bile: jaundice o Bile salts: itching • Reticulo-endothelial cells o Vulnerable to infection: patients = vulnerable to infection as liver = important site of immune response

Structural changes to the liver in cirrhosis

1) Patient sample taken➡sample correct volume, minimise contamination via aseptic technique 2) Sample handling➡fill in details on the label 3) Specimen transport➡transport sample to lab as quickly as possible 4) Incubation➡Incubate at 35-37 degrees C for 5-7 days, microbial growth is detected by monitoring CO2. If no growth, the sample is negative and discarded 5) Growth detection➡Time to positivity is usually 12-24 hours but may be shorter in overwhelming sepsis or longer with fastidious (complex nutritional requirement) organisms 6) Preliminary results➡blood culture is examined results are fed to the clinician to guide antibiotic therapy 7) Incubation➡culture is incubated on a range of mediums 8) Culture results➡results communicated to the clinician 9) Definitive results➡further overnight testing to get definitive results 10) Reporting Final summary released when all testing is complete

Structure of blood culture sampling

the deepest layer of the skin, under the dermis Adipose tissue with supporting fibrous bands (septa) Contains larger blood vessels

Subcutis

o Bilateral infection of submandibular space o Aggressive, rapidly spreading cellulitis without lymphaedenopathy with potential for airway obstruction o Requires careful monitoring and rapid intervention for prevention of asphyxia and aspiration pneumonia o Abscesses form: surgical drainage required, Antibiotics administered

Submandibular space infections (Ludwig's angina)

acute pancreatitis

Sudden onset of severe abdominal pain that radiates to the back and raised serum amylase

Suggested Ab: Clarithromycin 500mg 12 hours orally for 5 days Alternative Ab: Ciprofloxacin 500 mg 12 hours orally for 5 days

Suggested antibiotic and alternative antibiotic for campylobacter

Suggested: Ciprofloxacin 500mg 12 hourly for 5 days Alternative: discuss with microbiology

Suggested antibiotic and alternative antibiotic for salmonella

Suggested: Ciprofloxacin 500mg 12 hourly for 5 days Alternative: Azithromycin 500mg 24 hour orally for 3 days

Suggested antibiotic and alternative antibiotic for shigella

1. Sensitisation and memory induction: • Sensitisation to allergens and development of B-cell and T-cell memory. • Differentiation and clonal expansion of allergic-specific Th2 cells lead to the production of cytokines. • These induce immunoglobulin class switching to IgE. 2. Immediate phase - Type 1 reaction: • Immediate phase of an allergic reaction. • Release of histamine, prostaglandins, leukotrienes, chemokines and other cytokines. 3. Late phase - Allergic inflammation: • T cells are reactivated and clonally expand. • Local IgE is seen in allergic rhinitis and asthma but not in dermatitis. • Eosinophils are one of the main inflammatory cells in the lungs of asthmatics, but not in the skin of those with atopic dermatitis.

Summary of sensitisation and acute phase response

magnesium and phosphate

what disorders are often overlooked but can be serious?

- Suspected in patients with antecedent pharyngitis - Septic pulmonary emboli - Persistent fever despite antimicrobial therapy - Caused most commonly by fusobacterium necrophorum, often present in the bloodstream

Suppurative Jugular Thrombophlebitis (Lemierre's syndrome)

Origin of ovarian neoplasms

Surface epithelial tumour OR Germ cell tumour OR Sex cord stromal tumours

Member of breast MDT

Surgeons Oncologists Radiologists Pathologists Specialist nursing team Research nurses Genetic counsellors--test family with a history of BRCA1 and BRCA2 A group of experts with a specialist role in diagnosis, treatment and management of patients with breast cancer.

glucagon

what do alpha cells in the islet of langerhans in the pancreas make

Asymptomatic bacteriuria in pregnancy

Symptomatic UTI in pregnancy is frequently preceded by asymptomatic bacteriuria Prevalence is around 5% Untreated, at least 30% of women with ASB will develop acute pyelonephritis Screening for ASB is considered to be a cost effective approach to preventing pyelonephritis

How to diagnose a pneumothorax

Symptoms - small ones may be asymptomatic Breathlessness Pleuritic chest pain Signs Cyanosis Tachycardia Contralateral tracheal deviation in tension pneumothorax Percussion - hyperresonant Auscultation - reduced breath sounds Investigations to support the diagnosis Imaging - ultrasound, chest radiograph, CT Symptomatic pneumothoraces are often initially treated without further investigation

Severe pain, otorrhoea, granulation tissue in the canal floor, and cranial nerve palsies may be present. These patients should be promptly referred ENT Treat for a minimum of 6 weeks e.g. with iv ceftazidime then po ciprofloxacin

Symptoms and treatment of malignant (necrotising) external otittis

Burning up Chills, sweats, night sweats Rigors (feeling of cold with shivering when there is a rise in temp)➡patient doesn't lose consciousness unlike seizures; there is symmetrical shaking; feel hot and sweaty after and this is usually caused by infection

Symptoms associated with a fever:

Dyspnea: progressive and worsening Chronic cough Chronic sputum production

Symptoms of COPD

o Severe epigastic pain, sudden onset, radiating to the back

Symptoms of acute pancreatitis

Fever Loin pain Tachycardia Low BP

Symptoms of an upper UTI

Cough Fever Copious amounts of foul smelling sputum

Symptoms of bronchiectasis

Dyspnoea increasing for months to years Clubbing, fine crackles, dry cough Interstitial fibrosis and chronic inflammation with varying radiological and histological patterns Common end-stage fibrosed "honeycomb lung"

Symptoms of chronic interstitial lung disease

Anaemia Chronic diarrhoea Bloating Chronic fatigue

Symptoms of coeliac disease

fever, night sweats and shortness of breath Cardiac murmur on auscultation

Symptoms of infective endocarditis

• Often overlooked or disregarded • Symptoms of phosphate deficiency include: o Haemolysis, thrombocytopenia and poor granulocyte function o Severe muscle weakness, respiratory muscle failure and rhabdomyolysis o Convulsions, coma, death o Chronic phosphate deficiency will cause rickets (children) / osteomalacia (adults)

Symptoms of phosphate deficiency

Usually rapid onset Fever / chills Productive cough Mucopurulent sputum Pleuritic chest pain—stabbing pain on breathing in and out General malaise: fatigue, anorexia

Symptoms of pneumonia

• Leading clinical symptom: heartburn o Can be mistaken for cardiac chest pain • Hiatus hernia: abnormal bulging of a portion of the stomach through the diaphragm • Sliding hiatus hernia = reflux symptoms • Para-oesophageal hernia = strangulation • Both give rise to reflux • Para-oesophageal hiatus hernia can get trapped in the muscle and can lead to ischaemia and infarction of the stomach

Symptoms of reflux oesophagitis

Occurs more commonly in patients with pre-existing cardiac and lung disorders Cough, breathlessness, cyanosis Secondary bacterial pneumonia then may develop after an initial period of improvement caused by S.pneumoniae, H.influenzae, S.aureus

Symptoms of someone with primary viral pneumonia

insulin

what do beta cells in the islet of langerhans make

Diagnosis of pleural effusion

Symptoms: Breathlessness - effusion compresses the lung Little/no pleuritic pain - the visceral and parietal pleura are not in contact Signs: Percussion - dull Auscultation - reduced breath sounds Investigations to support the diagnosis: Imaging - ultrasound, chest radiograph, CT

combination of two drugs causes an effect that is greater than the sum of the individual effects of each drug alone

Synergism

o Lung crackles (*respiratory) o Meningism (*CNS) o Bony tenderness (*orthopaedic) o Skin erythema (*Skin and Soft Tissue) o Loin tenderness (*urinary)

System specific examination:

symptoms suggestive of infection and examination findings

System specific or non-specific

o Cough (*respiratory) o Neck stiffness (*CNS) o Bony pain (*orthopaedic) o Skin pain/redness (*Skin and Soft Tissue) o Dysuria (*urinary)

System specific symptoms

o Candida sp can infect almost any organ in the body o Defined by site of infection o Usually acquired from colonised skin or mucosal sites, or from GI tract o Usually seen in the compromised host o Candida albicans still most common, other species also occur o Disseminated disease may be identified from blood culture

Systemic candidosis

Injury may cause inflammatory mediator release Lose water, sodium chloride, albumin, energy substrates

Systemic capillary leak

• Jaundice • Oestrogen XS o Gynaecomastia o Spider naevi o Liver palms (red palms) o Testicular atrophy • Bruising • Pigmentation • Clubbing • Dependent oedema • Ascites • Encephalopathy • Osteomalacia/ osteoporosis

Systemic effects of liver disease

Increased susceptibility to viral, fungal, intracellular bacteria, and protozoan infections Ex. - DiGeorge Syndrome, Chronic Mucocutaneous Candidiasis

T cell deficiencies

• May be intracellular • BACTERIAL - Listeria monocytogenes (dairy products), Mycobacteria • VIRAL - transplants - HSV, CMV, VZV = herpes viruses. Serological testing, prophylaxis (preventative) and treatment with e.g. aciclovir and ganciclovir • FUNGAL - e.g. Candida spp., Cryptococcus spp. Pneumocystis spp.

T cell deficiencies--opportunistic pathogens

• Cryptosporidium parvum - oocysts shed by cattle/humans o Faecal oral route o Most patients recover after prolonged illness of up to 3 wks o May take much longer in T-cell deficient o Symptomatic treatment only (in most cases), do not usually give Abs to treat • Toxoplasma gondii o parasitic infection o Comes from cats or cats litter, pregnant women with cats need to be very careful once in contact o Wash hands thoroughly

T cell deficiencies: Protozoan and paristic infections examples

normal bone density

T score of -1 and above

just epithelium and mucosa

T1 tumour stage

• M = distant metastasis o cM0: no distant metastasis o pM1: distant metastasis • The more metastases, the higher the end stage

TMN in oesophageal cancer METASTASES

• pN = regional lymph nodes o pN0: no regional lymph node metastasis o pN1: regional lymph node metastasis in 1 or 2 nodes o pN2: regional lymph node metastasis in 3 to 6 nodes o pN3: regional lymph node metastasis in 7 or more nodes

TMN staging of oesophageal cancer NODES

• pT = depth of invasion of the primary tumour (how far through the muscularis propria, deeper connective tissue = worse) o pT1: tumour invades lamina propria, muscularis mucosae or submucosa o pT2: tumour invades muscularis propria o pT3: tumour invades adventitia o pT4: tumour invades adjacent structures - worse prognosis

TMN staging of oesophageal cancer TUMOUR

Metastasis is more important than lymph node involvement • pT1: intramucosal or submucosal • pT2: into muscularis propria • pT3: through muscularis propria into subserosa • pT4: through serosa (peritoneum) or into adjacent organs • pN0: no lymph node metastases • pN1: 1 to 2 lymph node metastases • pN2: 3 to 6 lymph node metastases • pN3: 7 or more lymph node mets • cM0: no distant metastases pM1: distant metastases present

TNM staging

Secondary hyperthyroidism

TSH decreased, low T4

T3 toxicosis or subclinical hypothyroidism

TSH decreased, normal T4

Types of viral transfusion transmitted infections and their risk

TTIs are extremely rare HIV=1 in 5.9 million donations Hepatitis B = 1: 2.2 million donations Hepatitis C = 1: 39 million donations Hepatitis E = risk is negligible

Nottingham prognostic index

TUMOUR SIZE, NODES, GRADE Can be used to give an indication of survival - in this system, tumour size is weighted less heavily than other major prognostic parameters Tumour Size x 0.2 + lymph node score (from table below) + grade score (from table below) 0 lymph nodes = 1 pnt 1-3 lymph nodes = 2 pnts >3 lymph nodes = 3 pnts Grade 1 = 1 pnt Grade 2 = 2 pnts Grade 3 = 3 pnts Grade + nodal status (0- score 1, 1-3- score 2 and 4 or more score 3) + 0.2 x tumour size) 3.4 or less -good 80%+ 16 year survival 3.41-5.4 -moderate 46% 5.41+ -poor 10%

somatostatin (inhibits growth hormone)

what do delta cells in the islet of langerhans make

Cell wall Protein synthesis DNA synthesis RNA synthesis Plasma membrane

Targets of an antimicrobial:

Why may test results vary for haematological samples?

Technical failure: e.g. clotted sample e.g. variation in reagents Normal: Intra-individual e.g. diurnal variation of cortisol levels Inter-individual e.g platelet count Abnormal What is normal?

anaphylaxis

Term for an acute potentially life threatening IgE mediated systemic hypersensitivity reaction?

o H. pylori antibody test (sens 92%, spec. 83%) - Insensitive, doesn't distinguish active from past infection o H. pylori stool Antigen (sens 95%, spec 94%) - Simple, non-invasive, inexpensive o Urea Breath test (sens 88-95%, spec 95-100%) - Expensive, pt experience, gold standard for test of cure o Biopsy Urease test (sens 90-95%, spec 95-100%) - Invasive, cross reactions • Stop PPI's before testing

Test for Helicobacter pylori to guide antibiotic treatment

genetic testing sweat test

Tests for cystic fibrosis

Coagulation screen and examples of a cogaulation screen

Tests measure the time taken for a clot to form when plasma is mixed with specified reagents Various parts of the coagulation cascade can be assayed Prothrombin Time Activated Partial Thromboplastin Time Thrombin Time

C-rays CT scans with PET

Tests to support the diganosis of infection

o Urine culture o Blood cultures o Renal ultrasound o Abdominal imaging o Abdominal fluid culture o Dental imaging o Faecal antigen (H. pylori) o Endoscopy o Ascitic tap for bacterial culture o Diagnostics Laparoscopy o Faecal toxin testing (C. difficile) o Hepatitis serology o Liver function tests o Faecal microbiology o Viral PCR on faeces o Sputum culture o Chest x-ray o Sputum culture for TB o Wound swab for culture o Bone sample for culture o Joint fluid for culture o Cardiac echocardiography o Lumbar puncture o CT/MRI o Brain biopsy for culture o HIV blood test o Serology-other

Tests you would perform for suspected infection

Symptomatic rehydration For immunocompromised: • Paromomycin (to kill parasite) • Nitazoxanide (effectiveness is unclear) • Octreotide (reduce cramps and frequency) • HIV patients, HAART should be quickly initiated

Treatment of cryptospiridosis

• Treatment = easy, Frequent venesection to deplete iron stores to normal, stops the progression of liver disease • Family members are screened using blood tests

Treatment of haemachromatosis

o Recognise pathogens o Mount an immune response which requires- cell- cell communication o Clear the pathogen: This may require adaptive responses to changing pathogen o Self-regulation: This is important to minimise host damage

The main physiological function of the immune system is to protect from infection, how does it do this?

Acyclovir for invasive disease of HSV like encephalitis (inflammation of the brain) For primary oral-labial or genital herpes Prophylaxis (preventatively) if you get frequent reactivations

Treatment of herpes simplex virus?

Tension pneumothorax

The perforation into the pleural cavity in an open or a closed pnemothorax can be valvular, allowing air into the cavity during inspiration but not out during expiration The pressure in the pneumothorax can rise above atmospheric pressure - think of blowing up a balloon This can compress mediastinal structures including the vena cavae and heart and move the mediastinum compressing the contralateral lung and can cause tracheal deviation A tension pneumothorax is potentially fatal and requires urgent treatment

Haemopoiesis

The physiological developmental process that gives rise to the cellular components of the blood A single multipotent haemopoetic stem cell can divide and differentiate to form different cell lineages that will populate the blood

Treatment of a pneumothorax

The pneumothorax may resolve spontaneously A tension pneumothorax can be decompressed as an emergency procedure using a needle inserted via an intercostal space With an open pneumothorax the penetrating chest wound causing it can be covered with an occlusive adhesive dressing that may incorporate a valve to allow air out but not in For any pneumothorax a chest drain tube can be inserted incorporating a valve to allow air out but not in, while the pneumothorax resolves For recurrent pneumothoraces pleurodesis is usually considered

Neuraminidase inhibitors oseltamivir (oral) and zanamivir (inhaled)

Treatment of influenza

Oncotic pressure

The pressure of water to move, typically into the capillary, as the result of the presence of plasma proteins like albumin.

What is screening?

The process of identifying people who appear healthy but may be at increased risk of a disease or condition

true

The rate of development of resistance is greater than the rate of development of new antibiotics

Sterilisation by the moist heat method

The risk of infection in surgical instruments is high, how should they be decontaminated?

o Drainage: Surgical or radiological o Combined with antimicrobial therapy o Antibiotics only really go to blood supply, oxygen therefore only given as an extra cover rather than main treatment

Treatment of intraperitoneal abscess

Describe granulocytes: neutrophils

These are phagocytes They are the most common white blood cell in adult blood (~ 10x10^9 per litre) Live for only a few hours in the blood

Full thickness burn Damage to epidermis, dermis and subcutaneous tissue Entire thickness of the skin is gone Does not hurt as you have burnt away all the pain receptors

Third degree burn

Transfusion Associated Circulatory Overload (TACO)

This can occur up to 24 hours after a transfusion Symptoms: sudden dyspnoea orthopnoea--breathless when lying flat tachycardia hypertension hypoxemia--low level of oxygen in the blood Signs: Raised blood pressure Elevated jugular venous pulse

Febrile non-hameolytic transfusion reactions

This is the most common reaction to a transfusion Self limited reaction FNHTR are due to cytokines or other biologically active molecules that accumulate during the storage of blood components This can occur during or soon after the transfusion Results in a rise of temperature more than 1 degree celsius from the base line ±rigors ± tachycardia Unpleasant but no life-threatening Resolves after discontinuation of transfusion

Follow up of UTI

Those who have recurrent UTI or abnormal imaging results should be assessed by paediatric specialist Those who do not require imaging do not need specialist assessment Asymptomatic bacteriuria does not require follow up Antibiotic prophylaxis should not be routinely recommended in infants and children following first-time UTI

Praziquantel (parazinoisoquinoline derivative) -40-60mg/kg with food 3 doses 8-hourly -Mechanism is unknown-->increased ionic permeability tetanic concentration, detachment, death -Well absorbed, extensive first pass metabolism, inactive metabolites excreted in the urine Treat long term complications

Treatment of schistosomiasis

endocrine gland that surrounds the trachea in the neck o Bilobed organ joined by an isthmus encased in a thin fibrous capsule located at the level of C5, C6, C7 vertebrae in the anterior neck in close proximity to the trachea o The thyroid gland on average weighs 18g for adult males and 15g for adult females o Anatomic relationships - next to the thyroid cartilage of the larynx, recurrent laryngeal nerve located in the tracheo-oesophageal groove close to posterior aspects of lateral lobes.

Thyroid gland

Wuchereria bancrofti

Tissue nematode example

Why should alternatives to blood transfusion be considered before giving a transfusion?

To conserve the blood supply and increase patient safety by avoiding clinically non-essential exposure to donor blood

What is the aim of breast screening?

To reduce mortality from breast cancer

Why would you transfuse fresh frozen plasma?

To replace clotting factors in patients with multiple factor deficiencies (acquired coagulopathies) i.e liver disease, disseminated intravascular coagulation etc You would transfuse fresh frozen plasma to treat significant bleeding in patients with abnormal clotting results AND to correct abnormal clotting results prior to invasive procedures

what symptoms does the centor criteria consist of?

Tonsillar exudate Tender anterior cervical lymphadenopathy Fever over 38 degrees celsius Absence of a cough

• Antiresorptive treatments: works on osteoclasts o SERMS: raloxifene o Bisphosphonates (first line therapy) - Oral therapy: alendronate, risedronate, ibandronate (weekly oral therapy) - IV therapy: zoledronate, ibandronate (once a year) o RANK-L inhibitor: Denosumab (most new drug, injections twice a year) • Anabolic treatments: parathyroid hormone analogue: teriparatide • Other treatments: strontium ranelate

Treatment options for the prevention of osteoporotic vertebral fractures

Infection from mother to baby during pregnancy (in utero) TORCH

Toxoplasmosis Others e.g. syphilis, HIV, coxsackie virus, hep B, varicella zoster Rubella Cytomegalovirus disease Herpes simplex disease

Non-immunological complications of a transfusion

Transfusion transmitted viral/prion infection Transfusion transmitted bacterial infection TACO (transfusion associated circulatory overload) Febrile non-haemolytic transfusion reaction (FNHTR) Haemochromatosis--overload of iron in the body

Diagnosis of puerperal endometritis

Transvaginal endometrial swabs although this is controversial

• An injury or wound to living tissue caused by an extrinsic agent o Road Traffic Accident, stabbing, gunshot wound, burns o Aneurysm repair, tumour excision, caesarean section, amputation of diabetic foot o What we know about trauma was mainly learnt on the battlefields o War = mortality of wounded reaching hospital gets lower the more advanced we get in machinery

Trauma

• Amount of new protein • Synthesised reduces and profile of proteins synthesised changes o Inc inflammatory modulators and scavengers (CRP, haptoglobin, clotting factors, modulators of clotting e.g. protease inhibitors) o Dec albumin • Skeletal muscle proteolysis increases o Inc free amino acids, transported to the liver for gluconeogenesis and protein synthesis o Inc plasma ammonia o Inc nitrogen loss: via urinary excretion of urea • In starvation, administration of adequate calories as carbohydrate/ lipid will stop muscle wasting • This is not true for trauma/ sepsis patients because the primary stimulation for protein breakdown is cytokine secretion from activated macrophages • Further proteolysis results in life-threatening damage to essential structural and secreted protein • Structural: respiratory muscle weakness results in poor cough, retention of secretions: pneumonia

Trauma protein turnover

Treatment of pleural effusions

Treat the breathlessness by removing the fluid Aspiration with a needle and syringe, ultrasound guided Reaspirate if the fluid reaccumulates For recurrent effusions consider a temporary or permanent pleural drain For recurrent effusions when the lung expands after drainage and the underlying cause remains consider pleurodesis to obliterate the pleural cavity Identify and treat the underlying cause Local Pleural fluid for cytology, microbiology, & biochemistry Pleural biopsy Systemic - investigate the systemic causes of pleural effusions

• Trigger: Agents Inhaled or blood or neural e.g. allergies, cigarette smoke • Abnormal (function +/- appearance) • Tubes: walls thickened or material in lumen narrowed/ blocked /damaged • Interface: thickened / lost • Change in function: o Tube blocked to air o Gas exchange impaired o Focus of inflammation o Tissue gone or scarred or thick mucus or contracted

Trigger and change in function of lungs

Diagnosis: Clinical and liver function tests Radiology Endoscopy Surgery Treatment: antibiotics and or surgery

Treatment and diagnosis of cholecystitis (inflammation of gall bladder)

o Pancreatic enzyme replacement (Creon) - Creon delayed release capsules: containing lipase, protease and amylase, made from pig pancreas o Nutritional supplements o Fat-soluble vitamins o High-calorie diet o Ursodeoxycholic acid o Maintain body weight o Avoid catabolic state o Introduce artificial feed early if sick • Adequate and appropriate nutrition is critical to a good outcome from trauma

Treatment for GI disease in CF

Mild disease-->topical antifungal therapy (self-diagnosis and treatment) of Terbinafine or Clotrimazole Severe disease-->systemic antifungal therapy (oral antifungal)

Treatment for a dermatophyte infection

Treatment is essential o Often necessitates changes to IV fluid regimens including TPN formulations o Give oral phosphate or IV phosphate

Treatment for acute phosphate deficiency

Antibiotics Immunoglobulin G replacement Blood product

Treatment for antibody deficiency

can be resected

Treatment for bronchiectasis that is localised

Identify the location of the cancer, surgeons remove with a little bit of normal either side Will re-join normal portions of the bowel together again to maintain normal intestinal cancer Works fine unless cancer is down at bottom of the rectum, where the anal sphincters are affected and therefore need to be removed = permanent colostomy Along with surgery can give additional treatment to make sure that more likely to recover Radiotherapy especially if cancer in the rectum and advanced Work with the radiology team and imaging to identify tumours that may respond to additional radiotherapy before surgery After surgery may give additional chemotherapy to reduce chances of cancer disseminating High risk factors as pathologists will try find these to see whether chemotherapy is needed from the sample that surgeons remove Mortality rates for bowel cancer patients have dec for both females and males Improvements in treatment: surgery, radiotherapy, chemotherapy, better radiology: imaging and pathology for staging the cancer MDTs coming together for weekly meeting to help come to justification of treatments for patients with the disease

Treatment for colorectal cancer

Median survival 41 years in the UK Physiotherapy Mucolytics Heart/lung transplants Why hasn't gene therapy worked?

Treatment for cystic fibrosis

Treatment is with combined chemotherapy for several months (usually 6/12) Notifiable disease & contact tracing Prevention: BCG given to infants & children in high prevalence areas (or parents & grandparents from high prevalence area)

Treatment for mycobacterium tuberculosis

Surgery o Symptomatic hypercalcaemia o In asymptomatic patients with primary HPT: - Calcium >0.25mmol/L above normal - Renal stone disease - Calculated creatinine clearance <60ml/min - Age <50 yrs - Osteoporosis at any site or history of fragility fracture • Medical o Calcimimetics (Cinacalcet) o Activates CaSR in the parathyroid gland - Therefore leads to reduced PTH secretion o Use to normalise calcium in symptomatic patients, or those who are not fit for or unwilling to have surgery o Does not seem to alter bone disease o No data on renal outcomes or quality of life

Treatment for primary hyperparathyroidism

o physiotherapy o exercise o bronchodilators o antibiotics: oral, nebuliser, IV o steroids o mucolytics (DNAse) o dec infection, dec inflammation

Treatment for respiratory disease in CF

topical antifungals or antibiotics

Treatment of Cheilitis

Metronidazole or tindizaole

Treatment of Giardiasis

Metronidazole single dose of 2g or in divided doses for 7 days Treat partner simultaneously

Treatment of Trichomoniasis

• Symptomatic: • Antihistamines. • Steroids. • Adrenaline. • Specific - immunotherapy (subcutaneous or sublingual): • Indications: o Life threatening reactions to a wasp or bee sting. o Severe hay fever. o Animal dander allergy. • Not helpful for: o Multiple allergies - more difficult to modulate the immune response. o Food allergy. o Allergic rashes - eczema, urticaria.

Treatment of atopic triad

dietary changes, surgical, motility, non-absorbable antibiotics.

Treatment of bacterial overgrowth

Why would you transfuse platelets?

Treatment of bleeding due to severe thrombocytopenia (low platelets) or platelet dysfunction Prevention of bleeding in patients with thrombocytopenia or platelet dysfunction

acyclovir antibiotic Treat all adults with chicken pox

Treatment of chicken pox and shingles (varicella zoster virus)

Antimalarials: • Non falciparum malaria-->chloroquine + primaquine (prevents relapse) • Falciparum malaria: Uncomplicated (oral regime): quinine + doxycycline, co-artem (artemther/lumefantrine), atovaquone - proguanil Complicated: IV quinine, artesunate (not currently licensed in EU) Supportive therapy: • Management of seizures, pulmonary oedema, acute renal failure and lactic acidosis • Exchange transfusion may be helpful in hyperparasitaemia

Treatments for malaria

• Haemoangioma o Benign angioma of blood vessels i.e. collection of small blood vessels that form a lump under the skin o 1% of the population o incidental finding on liver imaging o This does not only occur in the liver but can occur in other parts of the body • focal nodular hyperplasia o young females: 20-40 o a regenerative, arterliased nodule o more scarring, yellow in colour, too much oxygenated blood and therefore hepatocytes are massive

Tumours of blood vessels

Bronchopneumonia Lobar pneumonia

Two anatomical patterns of pneumonia

Histology of breast tissue

Two layers of cells: epithelial cells and myoepithelial cells Difficult to see myoepithelial cells, these may be malignant

Norovirus and rotavirus

Two most common viruses

o Autoimmune destruction of insulin producing beta cells in the islet of Langerhans o This can occur at any age but peaks around puberty o Equal sex incidence but after 15 years of age, there is a two fold increase in males o Incidence has increased by 3% to 4% in the last few years

Type 1 diabetes

• Acute infective colitis eg. campylobacter, shigella, salmonella, CMV • Antibiotic associated colitis including Pseudomembranous Colitis • Drug induced colitis • Acute ischaemic colitis: transient or gangrenous o Acute radiation colitis o Neutropenic colitis o Phlegmonous colitis

Types of acute colitis

Prolactinoma - Commonest, galactorrhoea (inapropriate production of milk) and menstrual disturbance-->treat with prolactin Growth hormone secreting - Gigantism in children, acromegaly in adults ACTH secreting - Cushing's syndrome

Types of anterior pituitary adenoma

Anti-TNF Anti-IL-6 (Tocilizumab) Anti-IL-1

Types of anti-cytokines

• Chronic idiopathic inflammatory bowel disease • Ischaemic colitis o Diverticular colitis o Microscopic colitis: collagenous & lymphocytic o Chronic infective colitis eg. amoebic colitis & TB o Diversion colitis o Eosinophilic colitis o Chronic radiation colitis

Types of chronic colitis

• Gastric body type • Intestinal type: specialised Barrett's mucosa • The difference between gastric cardia/body type of Barret's oesophagus and intestinal type is that the intestinal type has goblet cells which are typical of intestinal • Can get a mixture of the two • Premalignant condition = increased risk of developing adenocarcinoma • Regular endoscopic surveillance is recommended for early detection of neoplasia • Depends on severity of Barrett's how often endoscope

Types of columnar Mucosa: Barrett's oesophagus

• Non-specific: • Inflammatory markers. • Disease specific: • Autoantibody testing - disease specific. • HLA typing - what autoimmune diseases they are susceptible to

Types of diagnostic tests in autoimmune disease

• Corticosteroids • Cytotoxic/agents • Anti-proliferative/ activation agents • DMARD's • Biologic DMARD's

Types of drugs which cause immunosuppression

o Peptide hormones-->small hormones released from pituitary (e.g. PTH, ACTH, TSH) o Steroid hormones e.g. testosterone, oestradiol, cortisol o Tyrosine based hormones e.g. thyroxine T4 and triiodothyronine T3

Types of hormones

Primary Second

Types of maliganant lung tumours

neutrophils and macrophages • Neutrophils: short lived • macrophages: long lasting, firstly monocytes and go into bone marrow and become macrophages • Eat bacteria, fungi -> and then destroy them o Eat the bacterium and take into cell where phagosome is attacked by a lysosome to break it down, making a phagolysosome complex

Types of phagocytes

Community acquired Hospital acquired Ventilator acquired Aspiration pneumonia

Types of pneumonia

• Oral cavity - ulcerations. • Eye - pseudotumours and conjunctivitis. • Lungs - cavities, bleeds and lung infiltrates. • Nose - stuffiness, nosebleeds and saddle nose. • Heart - pericarditis. • Skin - nodules on the elbow and purpura. • Kidneys - glomerulonephritis.

Types of vasculitis

Typical organisms have a cell wall For example: -Streptococcus pneumoniae -Haemophilus influenzae -Moraxella catarrhalis -Staphylococcus aureus -Klebsiella pneumoniae

Typical causative organisms that cause community acquired pneumonia

Trichophyton rubrum T.interdigitale

Typical causes of tinea unguium

Bone marrow aspirate and trephine

Under local anaesthetic, liquid marrow is aspirated from the posterior iliac crest of the pelvis and a trephine (hole saw used in surgery) core biopsy is then taken with a hollow needle

Pleural fibrosis

fibrous tissue thickening of pleura due to chronic inflammatory diseases such as TB or asbestos, won't change shape when pt breathes/moves Can be unilateral or bilateral Can be localised or diffuse

Otitis media symptoms

Unusual Irritability Difficulty Sleeping Tugging or Pulling At One Or Both Ears Fever Fluid Draining From The Ear Loss Of Balance Unresponsiveness To Quiet Sounds or Other Signs Of Hearing difficulty

o Adverse reactions o Harmful eradication of normal bowel flora: which may predispose to CDI (clostridium difficile infections) o Increased excretion of salmonellae o Induction of verotoxin production (inc the risk of HUS: haemolytic-uremic syndrome) in E coli O157 - HUS: haemolytic uremic syndrome: anaemia (destruction of RBCs), kidney failure and low platelet count o Emergence of antibiotic-resistant pathogens

Unwanted effects of antibiotics

Urinary tract infections in children

Up to 7% of girls and 2% of boys experience a symptomatic culture-proven UTI prior to 6 years of age. Of febrile neonates, up to 7% have UTIs. Most UTIs in children are from ascending bacteria E. coli (60-80%), Proteus, Klebsiella, Enterococcus, and Staphylococcus saprophyticus The overall prevalence of UTI is approximately 5% in febrile infants but varies widely by race and sex. Caucasian children had a two- to fourfold higher prevalence of UTI as compared to African-American children Females have a two- to fourfold higher prevalence of UTI than do circumcised males

Nose Sinuses Mouth Pharynx Larynx

Upper respiratory tract consists of

-Cystitis presents with dysuria, frequency, urgency, suprapubic pain, and WBCs (but not WBC casts) in urine. -Primarily caused by ascension of microbes from urethra to bladder. -Males— infants with congenital defects, vesicoureteral reflux. -Elderly—enlarged prostate. Ascension to kidney results in pyelonephritis, which presents with fever, chills, flank pain, costovertebral angle tenderness, hematuria, and WBC casts. -Ten times more common in women (shorter urethras colonized by fecal flora). Other predisposing factors: obstruction, kidney surgery, catheterization, GU malformation, diabetes, pregnancy. PROSTATITIS EPIDIDMYO-ORCHITIS

Urinary tract infections

o Bacteria ascend from the genital tract and cause infection by colonisation o Or bacteria arise from catheterisation to cause infection o Women are more likely to get a UTI because they have a shorter urethra o Diabetics and those with damaged or abnormal urinary tracts are also more likely to get a UTI o Candiduria (isolation of candida from urine) is common - This may or may not be significant

Urinary tract infections caused by candida:

• Prehepatic: unconjugated bilirubin o no urinary bilirubin • Hepatic: hepatocellular o variable depending on degree of obstruction due to either disease or inflammatory oedema • Post-hepatic: obstruction o dark urine (& pale stools)

Urine tests with jaundice

o S.aureus o Bacillus cereus o Clostridium perfringens o Clostridium botulinum o Salmonella gastroenteritis

food intoxcations

Malignant mesothelioma immunostaining

Uses antibodies linked to a dye to identify antigens is cells Mesothelial cells and epithelial cells tend to express different antigens allowing them to be differentiated from each other There is some cross reaction therefore a panel of 4 or more antibodies is used Mesothelium-associated antigen stains on the left, top - cytokeratin 5 middle - Wilms tumour antigen bottom - calretinin

• Autoimmune diseases o Connective Tissue Disease, vasculitis, RA • Inflammatory diseases o Crohn's, sarcoid, GCA/polymyalgia rheumatica • Malignancies o Lymphoma • Allograft rejection

Uses of immunosuppressive drugs

Allows for: Evaluation of bone turnover and bone loss Evaluation of treatment effect-->CTX used to monitor response to anti-resorptive therapy Evaluation of compliance with medication-->P1NP used to monitor compliance with teriparatide CTX used to monitor compliance/response to anti-resorptive therapy

Uses of new bone markers

Spine, pelvis, femur Humerus, skull

Usual sites of spread of bone metastases

Types of prion transfusion transmitted infection

Variant Creutzfeldt-Jakob disease This has unknown risk No case since 1999 Prevention: Universal leucodepletion since 1999 Import plasma from countries with low incidence of vCJD Inactivate prions with methylene blue

A complication of VZV (chicken pox) infection Rare in children, significant morbidity & mortality in adults with varicella Those at greatest risk are the immunocompromised, adults with chronic lung disease, smokers and pregnant women*. Insidious onset 1-6 days after the rash has appeared with symptoms of progressive tachypnoea, dyspnoea, and dry cough. Tests: Chest X-ray typically reveals diffuse bilateral infiltrates Treatment: Supportive & prompt administration of IV acyclovir

Varicella Zoster virus pneumonia

Vulval intraepithelial neoplasia

Varied clinical appearances of VIN. From left to right: warty, white patches, pigmented patches, visualised by painting with toluidine blue.

Looks like the tissue of origin o Uncommon 1-2% all pancreatic neoplasms o Any age, rare in children o 7-13% multiple (MEN-1) o 15-35% non-functioning o Single tumours often produce multiple hormones but usually single hyperfunctional syndrome

Well-differentiated neuroendocrine tumour

- Heart Valves (endocarditis)- Native, Prosthetic - Vessels- Mycotic aneurysms, Prosthetic Vascular Graft Infections (PVGI)

Vascular infections

Subgroup of hospital acquired pneumonia Pneumonia developing more than 48 hours after ET intubation and ventilation Pseudomonas spp may be implicated

Ventilator acquired pneumonia

Chickenpox (HHV3) Herpes simplex (HHV1/2) Enterovirus

Vesicular rashes

Influenza A and B Adenovirus Varicella zoster virus

Viral lower respiratory tract infections adults get after they pneumonia

Respiratory syncytial virus (like a cold) Parainfluenza (like a cold)

Viral lower respiratory tract infections children get after pneumonia

Influenza A and B Adenovirus Varicella zoster virus Respiratory syncytial virus Parainfluenza Measles Herpes simplex virus Cytomegalovirus Varicella zoster virus HHV-6

Viral lower respiratory tract infections immunocompromised hosts get who already have pneumonia

plasmid--circular transferable DNA Plasmids ofetn carry multiple antibiotic resistant genes, so CPEs are often resistant to many other antibiotics

What are CPEs coded for by

o Collective name for a number of species of α-haemolytic streptococci that inhabit the upper respiratory tract e.g. S. oralis, S. mitis o Classic cause of sub-acute bacterial endocarditis

Viridans streptococci

1. Adsorption (of virion to host cell) 2. Penetration (of nucleocapsid to host cell) 3. Uncoating-->nucleic acid is released from phagosome 4. Synthesis (of viral components) 5. Assembly (of viral components into progeny virions) 6. Release (of progeny virions from host cell either by budding off or by disintegration of the host cell)

Virus life cycle:

Carbapenemase producing enterobacteriacae which are bacteria able to produce an enzyme which breaks down many beta lactam antibiotics including carbapenems

What are CPEs?

1. Virus attaches to cell via a receptor 2. The virus enters the cell 3. The virus uncoats where the genome is released from the capsid 4. Early proteins are produced—viral enzymes 5. The virus replicates using the host's replication method 6. Late transcription/translation in the host cell-->produces viral structural proteins 7. The virus assembles ready to be released 8. The virus is released and matures

Virus life cycle

o Rotavirus o Norovirus o Astrovirus o Sapovirus o Adenovirus (group F)

Virus syndromes--gastroenteritis

Encephalitis/meningitis: HSV Enteroviruses Rabies Japanese encephalitis virus Nipah virus

Virus syndromes--neurological disease

o Influenza A/B o Respiratory syncytial virus o Parainfluenza virus o Human metapneumovirus o Rhinovirus o Coronavirus

Virus syndromes--respiratory infections

The unique proteins are vital for virus replication and infectivity, these unique proteins are targets for molecular inhibition (anti-viral activity)

Viruses encode unique proteins, what are they needed for?

o Environmental cleaning and decontamination - H2O2 room decontamination - Spillage management - Laundry o Equipment decontamination - Sterilisation - Disinfection o Antisepsis - Surgical skin prep - MRSA decolonisation o Antibiotic prophylaxis - Perioperative - Post-exposure

Ways to eliminate the pathogenic organism in infection control

Protein synthesis inhibitors of bacteria o Macrolides, Lincosamides, Streptogramins - E.g. Erythromycin, clarithromycin (macrolides) - Clindamycin (lincosamide) - Bind to 50S ribosomal subunit - Inhibit protein elongation

What are MLS antibiotics?

Protein synthesis inhibitors of bacteria E.g. gentamicin, amikacin Binds to 30S ribosomal subunit Mechanism of action is not fully understood

What are aminoglycosides?

treat both gram positive and gram negative acitvity

What are beta lactams used for?

They are classified as immunomodulating agents; this means that they act on the immune system to reduce skin inflammation. Both tacrolimus and pimecrolimus block a chemical called calcineurin which activates inflammation in the skin causing redness and itching of the skin.

What are calcineurin inhbitors?

o Cross-linking molecules which are released with bone resorption, correlate highly with bone resorption o Increased in periods of high bone turnover like: - Hyperthyroidism - Adolescents - Menopause o Have diurnal; variation o Do not predict bone mineral density o Decrease with anti-resorptive therapy

What are collagen cross links (NTX, CTX)?

fungi causing superficial skin lesions They are groups of slow growing moulds seen as causes of disease in skin, hair and nails

What are dermatophytes?

Vital to the treatment and prevention of infection Done well, they can save lives, time and money Done poorly, they can result in loss of life, time and money

What are infection tests used for?

Protein synthesis inhibitors in bacteria o Linezolid: - Inhibits initiation of protein synthesis - Binds to 50S ribosomal subunit - Inhibits assembly of the initiation complex - May also bind to 70S subunit

What are oxazolidinones?

These are drugs which mimic the structure of pyrimidine and are used to treat cancer by interefring with DNA replication Thymidine analogues Cytosine anaolgues

What are pyrimidine analogues?

infective endocarditis

What are splinter haemorrhages a sign of?

• Congenital o Rare: T helper dysfunction +/= hypogammaglobulinaemia • Acquired o Drugs e.g. ciclosporin after transplantation (decs graft vs host disease and rejection), steroids o Viruses e.g. HIV

What are the 2 causes of t cell deficiencies?

Vaccinations Access to clean water

What are the 2 most effective public health medical interventions?

IgM, IgG, IgA, IgE

What are the different types of antibody?

Risk of under treatment if traditional antibiotic is given in an era where resistance is high Risk of excessively broad spectrum treatment if risk of resistance is taken into account

What are the implications for antibiotic use in empiric therapy?

First part of the duodenum Junction of antral and body mucosa Distal oesophagus (GOJ)

What are the major sites affected by peptic ulcer disease?

o To inform antibiotic therapy o First-line antibiotic choice if infection does not require immediate treatment - E.g. infectious endocarditis, osteomyelitis (unless patient is septic) o Second-line choice after empiric therapy o 'Start smart then focus' o Second line choice after failure of initial therapy - To inform local guidelines and antibiotic choices - To provide epidemiological data - To provide early warning of threats to public health Uncomplicated UTI in general practice o To provide epidemiological data - 'surveillance' o Sensitivity results are collated locally, nationally and internationally

What are the uses of sensitivity testing?

Mupirocin Fusidic acid

What are two other antibacterial protein synthesis inhibitors?

o Nucleic acid (DNA or RNA) o Protein (coat-structural, enzymes—non-structural) o +/- lipid envelope

What are viruses made up of?

Understanding disease Compared to normal physiology Design tests appropriate to clinical requirements Develop effective therapies

What can biochemical knowledge help with?

MRSA is resistant to flucloxacillin Can't use most beta lactams to treat MRSA But you can still use vancomycin which is a glycopeptide

What can't be used to treat MRSA and what can be used?

Tinea unguium

What causes onychomycosis?

small cell lung carcinoma

What condition is paraneoplastic cushing's seen in?

• Clacineurin: serine/threonine phosphatase • CyA o Binds to intracellular protein cyclophilin o From fungi imperfecti found in soil samples from a high treeless plain in S Norway called Hardanger Vidda o The lipophilic macrolide product of Streptomyces tsukubaensis, tacrolimus • Tacrolimus (FK506) o Binds to intracellular protein FKBP-12 • Mode of action o Prevents activation of NFAT o Factors which stimulate cytokines (i.e. IL-2 and IFNγ) gene transcription • T cell effects o Reversible inhibition of T-cell activation, proliferation and clonal expansion

What do Calcineurin inhibitors do?

DNA viruses convert the DNA to DNA in eukaryotes OR they convert DNA to RNA, this virus cannot be inhibited because it would have an effect on the eukaryotic cell

What do DNA viruses do? Can they be inhibited?

Convert RNA to RNA This can be inhibited

What do RNA viruses do? Can they be inhibited?

Antibacterials Antifungals Antivirals o These can include antibiotics o Synthetic compounds with a similar effect o Semi-synthetic—modified from antibiotics o Different antimicrobial activity/spectrum, pharmacological properties or toxicity

What do antimicrobial agents include?

o Cell wall-->useful as human cells do not have this so antimicrobials are designed to attack these without damaging human cells o Cell membrane o DNA o Synthetic functions—protein synthesis

What do bacteria and fungi have in conmmon?

- Trying to figure out what antibiotic works against what pathogen - Looks for the biggest kill zone - Tell if antibiotic is sensitive, intermediate, or resistant

What is sensitivity testing?

inhibit bone resorption by killing osteoclasts • Mimic pyrophosphate structure of bone • Taken up by skeleton • Ingested by osteoclasts • Lives for years and kills the osteoclasts • Stops resorption • Drugs with consequences: bone pain, thickened cortex and can cause an atypical femur fracture, straight across: drug related fracture • Stop osteoporotic fractures but can cause horrible atypical fractures

What do bisphosphonates (drugs) do?

pancreatic polypeptide

What do f cells in the islet of langerhans secrete?

Inhibit reverse transcriptase i.e. they inhibit DNA-->RNA

What do nucleoside reverse transcriptase inhibitors do?

botulism-->can cause paralysis

What does C.botulinum cause?

classcial cause of gas gangrene

What does C.perfringens cause?

tetanus

What does C.tetani cause?

2 nucleoside reverse transcriptase inhibitors + non-nucleotide reverse transcriptase inhibitor OR 2 nucleoside reverse transcriptase inhibitors + boosted protease inhibitor (like ritonavir) or an integrase inhibitor

What does HAART consist of?

co-amoxiclav and clarithryomycin

What does Strep pneumoniae have fewer side effects to?

(e.g. 0.1mg/L)=sensitive organism-->i.e. less drug required to inhibit the organism's growth o But sensitivity actually depends on the level available at the site of infection

What does a low MIC mean?

Failure to develop regulatory T cells which causes severe autoimmunity from birth

What does a mutation in FOXP3 result in?

T cells to be activated more easily which gives a stronger immune response in general

What does a mutation in PTPN22 cause?

Makes proteins more immunogenic, this occurs in rheumatoid arthritis

What does citrullination (change of amino acid arginine to citrulline) of proteins cause? What condition does this cause?

Inhibits cell wall synthesis This is only active against gram positive bacteria

What does flucloxacillin do?

Impaired fasting glucose, this is prediabetes and puts one at greater risk of developing diabetes

What does it mean if a patient's fasting glucose if between 6.1-6.9?

It is not resistant to the antibiotic and is susceptible

What does it mean if bacteria has a zone of inhibition around it?

bloodstream infection that can or cannot affect the CNS

What does meningococcal septicaemia affect?

Alters gluten to help it bind to HLA-DQ This occurs in Coeliac disease

What does tissue transglutamase do? What condition does this occur in?

Lamivudine In the presence of Lamivudine, the rare population of strains with this mutation will predominate

What drug does the M184V mutation give resistance to?

• Season • Latitude/climate • Clothing • Use of sunscreen • Time spent indoor/outdoors • Skin tone • Age • Diet • Body fat and BMI • Malabsorption

What factors affect your vitamin D level?

• C2, C4 deficiency: SLE, infections, myositis • C5-C9 form membrane attack complex o Presents with repeated episodes of BACTERIAL meningitis, particularly Neisseria meningitis

What happenes if you have a deficiency in complement?

Adverse events increase Failure rates decrease but there are diminishing returns

What happens as the duration of antibiotics increases?

Develops in the tongue-->lingual thyroid

What happens if the thyroid gland fails to migrate in development?

forms a mass in the mediastinum

What happens if the thyroid migrates too much in development?

• Glycogenolysis: 24hrs max o Glycogen - > glucose • Gluconeogenesis o Skeletal and secreted protein breakdown o 1kg muscle = 200g protein = 120g glucose o amino acids - > glucose and lactate production o nitrogen loss: 60-70g/day but can be up to 300g • Lipolysis and ketogenesis o FFA - > acetyl CoA - > acetoacetate and hydroxybutyrate o Gradual change to ketone metabolism by CNS which spares protein stores and muscles o Ketones are acids and cause a diuresis with loss of water and electrolytes

What happens when the supply of glucose and oxygen is interrupted after trauma?

Through muscularis mucosa into the submucosae

What have neoplastic cells invaded through?

Clavulonic acid

What inhibits beta lactamases?

• ACPA is more specific (95%) for RA than RF. • Similar sensitivity to RF. • Useful prognostic marker - can monitor the auto-antibodies over time to see if it goes up or down. • ACPA positive patients tend to have more severe and erosive disease. • Similar process to before. Antigen on a plate etc....

What is Anti-CCP Antibody?

Common variable immunodeficiency People with CVID are highly susceptible to infection from foreign invaders such as bacteria, or more rarely, viruses and often develop recurrent infections, particularly in the lungs, sinuses, and ears. Pneumonia is common in people with CVID.

What is CVID?

7 transmembrane GTP binding protein As calcium levels rise, the parathyroid senses this via the CaSR and switches off or reduces PTH secretion If this doesn't happen, then this results in hypersecretion of PTH and non-supressibility of PTH

What is CaSR?

Collection of signs and symptoms due to prolonged exposure to cortisol Exogenous causes--excessive glucocorticoid medication Endogenous causes--adrenal cortical tumours, adrenal cortical hyperplasia and ACTH secreting pituitary adenoma

What is Cushing's syndrome a result of? What are the endogenous and exogenous causes?

condition in which bulging pouches in the gastrointestinal tract (usually lower part of the large intestine) push the mucosal lining through the surrounding muscle o Asymptomatic (90 - 99%) o Cramping abdominal pain o Alternating constipation and diarrhoea o Acute and chronic complications ( 10 - 30 % )

What is Diverticular disease? What are the clinical features?

E.Coli is part of the normal bowel flora in most humans E.Coli can colonise the urethral meatus and surrounding area Females have a shorter urethra E.Coli are able to adhere to uroepithelial cells/urinary catheter materials Triggers host inflammatory response Able to develop resistance to antibiotics

What is E.coli and how can it cause infection?

HIGHLY ACTIVE ANTIRETROVIRAL THERAPY combination of retroviral drugs. *Decreases viral load, at times, to undetectable levels* HAART often uses fixed drug combinations i.e. more than one drug in a pill The aim of HAART is to switch off virus replication HIV patients require lifelong treatment

What is HAART?

Dependent on Hep B Virus for infection. Superinfection upon existing HBV infection is more severe than coinfection.

What is Hepatitis D?

mild; most common immunodeficiency Pts develop recurrent respiratory or GI infxns Anaphylactic transfusion rxn due to anti-IgA abs More prone to autoimmune disease

What is IgA deficiency?

Low calcium High phosphate High calcium results in negative feedback on PTH release (via calcium sensing receptors of the parathyroid gland)

What is PTH stimulated by?

PanIN--pancreatic intraepithelial neoplasia Neoplasm within the ducts of the pancreas Most common neoplastic precursor to invasive pancreatic cancer Similar progression to adenoma-carcinoma sequence in the colon

What is PanIN?

o Up to 50% of people have S. aureus in their nasal carriages o S. aureus is able to adhere to damaged skin o Produces exoenzymes and toxins that can damage tissues and provoke a host response (e.g. pus formation)

What is S.aureus and how does it cause skin infections?

Hepatitis C RNA polymerase nucleotide inhibtor

What is Sofosbuvir?

Number of standard deviations you are from a young healthy person

What is T score?

PIPERACILLIN + TAZOBACTEM This is the same concept as co-amoxiclav which inhibits beta lactamases

What is Tazocin?

Primary antibody deficiency Suspicion confirmed with genetics The white blood cell formation process does not generate mature B cells. This manifests as a complete or near-complete lack of proteins called gamma globulins, including antibodies, in their bloodstream

What is X-linked ammaglobulinaemia?

Isolation of a viable pathogen This enable: Identification➡immediate or by further testing Typing➡to establish organism relatedness Sensitivity testing➡to direct antimicrobial therapy This is not applicable to non-cultivable microorganisms Needs to be done before antibiotics are started

What is a bacterial culture? What does it enable?

Kills most types of bacteria/fungi encountered

What is a broad spectrum antimicrobial?

Inflammation It can be a sign/symptom of infection

What is a fever a sign of?

Body temperature above 38 degrees celsius

What is a fever?

most widley used stain, involves decolorization w/ alcohol that removes color from the cells with the thinner gram negative cell wall. Gram positive stain black/purple Gram negative stain red (colour of counter stain)

What is a gram stain?

cystitis

What is a lower UTI?

• Calcium > 3.5 mmol/L or < 1.6 mmol/L is a medical emergency requiring immediate treatment

What is a medical emergency in calcium levels?

Kills only a narrow range of organisms

What is a narrow spectrum antimicrobial?

source that allows the organism to survive and multiply

What is a pathogenic reservoir?

the membrane-enclosed organelle which forms when a phagosome fuses with a lysosome • Bacterium been ingested via phagosome and is attacking with the lysosome • O2 -> O2- (superoxide) -> hypochlorous acid (bleach, to kill the pathogen) • NADPH complex formed of several proteins including gp91phox (coded by the X chromosome) donates the electron to oxygen to make it a superoxide Bug is taken up by phagocyte and bleach is poured on it to get rid of the pathogen Need functioning phagocytes

What is a phagolysosome? What does it do?

Herpes virus polymerase inhibitor Varicella zoster virus Herpes simplex virus

What is acylobvir and what is it used to treat?

ENT, respiratory and urinary infections

What is amoxicillin used to treat?

Acquisition of a gene that encodes an antibiotic resistant mechanism New mutation Horizontally transferred The gene (mutation) is usually an antibiotic modifying enzyme or a target alteration

What is an acquired resistance mechanism of bacteria?

Benign primary liver tumour Benign proliferation of liver cells May be mutliple (adenomatosis) Often driven by exogenous steroids e/g/ OCP, anabolic steroids May rupture causing haemoperitoneum

What is an adenoma of the liver?

Antigens that initiate an IgE mediated response First encounter results in innate and IgM response

What is an allergen?

The GI tract is from mouth to anus Bacteria from within the GI tract can cause infections in other body systems e.g. a perforated oesophagus can result in an infection in the respiratory system infections in one body stsem can also extned to another body system e.g. an intra-abdominal infection can result in a fistula into the urinary tract

What is an infection of the GI tract?

pyelonephritis

What is an upper UTI?

Choosing the right antibiotics and administering them in the right way every time as an effort to slow the spread of Multi-drug resistant organisms Start wth broad spectrum, then when the organism is known thorugh culture, focus down with a narrow spectrum antibiotic

What is antibiotic stewardship?

penicillin

What is strep pneumoniae sensitive (can be killed by) to?

Affecting subcutaenous tissue usually following traumatic implantation

What is subcutaneous fungal infection?

chronic inflammatory disorder of the airways • Disease of inflammation and hyper-reactivity of small airways. • In childhood - aero-allergic stimuli - house dust mite key pathogenic importance. • Immediate symptoms are IgE-mediated. • Damage to airways due to late phase response. • Damaged airways are hyper-reactive to non-allergic stimuli. E.g. fumes.

What is asthma?

• The immune system should be tolerant to self-antigens: • I.e. Not identify them as something that needs to be attacked. • Any part of the immune system that could attack self should be eliminated. • If it is not eliminated then autoimmune disease results.

What is autoimmune disease?

• Bone is composed of: o Cortical bone o Trabecular bone o Cells o Extracellular

What is bone composed of?

tooth decay o bacterial plaques form on the tooth surface and form caries o acid produced by bacteria (Streptococcus mutans and lactobacillus spp) is believed to erode the enamel and bone o bacteria can now move inside the tooth when within the pulp cause inflammation = swelling and acute pain = common reason for unplanned visit to a dentist o require fillings

What is caries?

o Environmental decontamination (surfaces, spills etc.) o Antisepsis o Heat-sensitive items

What is chemical disinfection largely limited to?

Used against beta lactamase producers

What is co-amoxiclav used for?

AMOXICILLIN + CLAVULONIC ACID

What is co-amoxiclav?

Anti-tubercukous agent used to inhibit cell wall synthesis

What is cyloserine?

Detection of the whole organism through microscopy OR detection of a component of the organism e.g. antigen or nucelic acid like DNA or RNA

What is direct detection of an organism?

Inflammation of the brain usually viral-->Herpes virus

What is encephalitis? What is it caused by?

Staphylococcus aureus infections

What is flucloxacillin used to treat?

Used mainly to treat gram negative UTI Inhibits cell wall synthesis

What is fosfomycin?

Ganciclovir is a herpes polymerase inhibitor Inhibits: Cytomegalovirus Huma herpes 6 Herpes simplex Varicella zoster

What is ganciclovir and what is it used to treat?

As part of the investigation of sepsis: Blood cultures FBC, U&Es, LFTS, clotting, CRP

What is general sampling?

Activities undertaken with the aim of breaking the chain of infection: o Eliminates the pathogenic organism o Remove reservoir o Minimise transmission o Eliminate exit and entry o Reduce susceptibility to infection e.g. vaccination

What is infection prevention and control?

Infection of the heart valves Most commonly caused by staphylococcus aureus and streptococci (especially alpha haemolytic strep)

What is infective endocarditis and what is it caused by?

Sample from the source of infection Assist with diagnosis Tells you what bug is causing the infection and what drug to treat the patient with

What is local sampling?

Inflammation of the meninges Caused by viruses, bacteria, mycobacteria, fungi, parasites

What is meningitis?

Probably a myeloma which results in a metastatic growth causing spinal cord compression This is a medical emergency Treat with steroids and radiotherapy to preserve their ability to walk

What is metastatic spinal cord compression? How would you treat it?

Necrotizing fasciitis (NF), commonly known as flesh-eating disease, is an infection that results in the death of parts of the body's soft tissue. It is a severe disease of sudden onset that spreads rapidly. • Rapidly spreading synergistic infection • Surgical Emergency, high mortality • Debrided tissue / Pus- M, C and S • Blood Cultures (2 sets) • Bloods: FBC, U&E's, LFT's, CRP •

What is necrotising fascitis

N-acetyl muramic acid (NAM) and N-acetyl glucosamine (NAG)

What is peptidoglycan made of?

- Progression of gingivitis with progressive loss of dental support structure function. - May require antibiotics in addition to cleaning

What is periodontitis? How do you treat it?

-Sore throat due to viral or bacterial infection -Accompanied by otitis media (ear inflammation) in severe cases -pain when swallowing; referred to ear Majority are viral Send throat swabs only if there is evidence of bacterial infection--looking only for B haem streps Additional tests: EBV serology Swab for diptheria Pus if quinsy abscess

What is pharyngitis? How do you investigate it?

Inflammation of the lungs, caused by bacteria or virus (most common) or by aspiration of foreign substances into lower respiratory tract. Infection affecting the most distal airways and alveoli Resulting in the formation of inflammatory exudate

What is pneumonia?

Commonly seen in RA; IgM, IgG or IgA autoantibody against Fc portion of IgG that is a marker of tissue damage and disease activity • Commonly found in rheumatoid arthritis but not diagnostic of the diseases (sensitivity and specificity around 70% so can't be 100% sure that it's RA). • Can be seen with other diseases in which polyclonal stimulation of B cells is seen (chronic infections).

What is rheumatoid factor?

inflammation of the mucous membranes of the nose • Allergic/non-allergic. • Allergic: o Perennial - all year. o Seasonal - self-explanatory. • Blocked nose, runny nose, sneezing and itchy nose. Often with eye symptoms (itching/burning, watery eyes, redness). • House dust mite, animal dander, pollens. • Treatment: o Anti-histamines. o Nasal steroids.

What is rhinitis? how do you treat it?

Deposition of new bone This occurs in the prostate, breast/lung (15-25%) and in cancers like lymphoma

What is sclerotic/osteoblastic bone metastases?

Target should not be present in the human host or is inaccessible in the human host cell .e.g cell wall

What is selective toxicity of an antimicrobial?

Clinical diagnosis, viral and bacterial, send pus if ear drum perforated

how would you investigate acute otitis media?

o Infectious (not the most common) - Bacterial, viral (Herpes: HSV1, Cytomegalovirus: CMV: seen mostly in immunosuppressed), fungal (candida) o Chemical - Ingestion of corrosive substances: especially children - Reflux of gastric contents • commonest cause • stomach contents works through sphincter into lower oesophagus, sometimes upper oesophagus

What is the aetiology of oesophagitis?

Range of bacterial/fungal species likely to be sensitive to a particular antibacterial/antifungal agent

What is the antimicrobial spectrum?

N.meningitidis

What is the cause of meningitis in children and young adults?

Strep. pneumoniae

What is the cause of meninigitis in elderly patients?

o β-1,3-glucan makes up chitin - Large polymer of UDP-glucose - 50 60% of the dry weight of the fungal cell wall - Form a fibrous network on the inner surface of the cell wall - Synthesized by β-1,3-glucan synthase - No cell wall in animal cells - Ideal potential for selective toxicity

What is the chitin made of?

• Allergen requires processing. • Presentation to T cells and cytokine release. • Results in delineation of T-helper subsets into different types

What is the conventional immune response?

• Granular fluorescence of neutrophil cytoplasm with nuclear not fluorescent. • Target antigens - PR3 (90%) and MPO. • WG is this one. Jump to search Perinuclear staining typical of p-ANCA The granular, cytoplasmic staining pattern of c-ANCA Immunofluorescence staining pattern of ANCA. Anti-neutrophil cytoplasmic antibodies (ANCAs) are a group of autoantibodies, mainly of the IgG type, against antigens in the cytoplasm of neutrophil granulocytes (the most common type of white blood cell) and monocytes. They are detected as a blood test in a number of autoimmune disorders, but are particularly associated with systemic vasculitis,

What is the cytoplasmic ANCA pattern?

Common in general adult population, probably a 5-25% rate, increasing incidence in elderly people

What is the incidence of fungal nail infections?

Patient's own colonised mucosa

What is the infection of candida usually from?

Microscopy and culture

What is the investigation for dermatophyte infection?

Recreational water Animal contact Poor hand hygiene

What is the main cause of food bourne diseases?

high insulin inhibits liver gluconeogensis

What is the metabolic effect insulin has?

Strep pneumoniae

What is the most common community cause of pneumonia?

Insulinoma

What is the most common neuroendocrine tumour?

Heat and should be used where possible

What is the most hazardous method of disinfecting?

Increased serum Ca and decreased serum PO4

What is the net effect of PTH?

The response when an antigen enters the body for the first time. Develops in the weeks following first exposure to an anitgen mainly the IgM antibody

What is the primary immune response?

Kills most bacteria including normal flora which allows others, possibly pathoegnic species to overgrow as there is less compeititon

What is the problem with a broad spectrum antibiotic?

predicts probability of cure with surgery, likelihood of tumour recurrence and site of recurrence, and determines selection of patients for adjuvant therapy

What is the purpose of Dukes staging/TMN?

The immune response generated upon secondary and subsequent encounters with a pathogen. The secondary immune response is faster and more powerful-->mainly IgG antibody

What is the secondary immune response?

Antibiotic very similar to Tetracycline with a similar mechanism of action and a much broader spectrum

What is tigecycline?

can be uni or bilateral itching, flaking, fissuring of skin between toes (interdigital) Interdif=gital toe web skin is wet and macerated Plantar surface of the foot is dry and scaly, if the skin of the whole foot is affected-->'Moccasin foot' May spread to infect toe nails Hyperhidrosis-->secondary to infection, may increase severity Secondary bacterial infection

What is tinea pedis?

One of the major causes of primary antibody deficiency. It describes the period of time between the maternal Igs being degraded and the baby developing its own set of Igs.

What is transient hypogammaglobulinaemia?

Females are carriers and males are affected A patient presenting with hyper IgM syndrome may be affected by simple infectious organisms in exposed regions like the respiratory system Fever (recurrent infections) Low counts of IgA, IgG and IgE antibodies CD40L not reactive in T cells Recurrent sinopulmonary and GI infections with pyogenic bacteria and opportunistic organisms, and cutaneous manifestations including pyodermas extensive warts

What is x-linked hyper IgM syndrome?

STERILISE

What method of cleaning would you use for a device that will enter sterile body areas or break the skin?

DISINFECT

What method of cleaning would you use for devices that will contact mucous membranes or will be contaminated with body fluids?

meningitis

What only affects the CNS?

• Echinococcus sp. • MACROPARASITE • Platyhelminth—cestode—tapeworm • Human is an accidental host • The human who is usually the definitive host is the intermediate host in this life cycle • Usual hosts are sheep and dogs that eat contaminated raw meat • Found all over the world wherever sheep are farmed

What parasite causes hydatid disease?

Alpha cells-25% Beta cells-75% Delta cells-5%

What proportion of islet cells do alpha, beta and delta cells make up?

culture tests

What should be taken before antibitoitcs are given?

virus commonly associated with cervical cancer

human papilloma virus

Bronchioles distended with mucus Hyperplasia mucus secreting glands Multiple repeated infections Severe chronic bronchitis and bronchiectasis Exocrine gland ducts plugged by mucus Atrophy and fibrosis of gland Impaired fat absorption, enzyme secretion, vitamin deficiencies (pancreatic insufficiency)

What structures are affected in cystic fibrosis?

Blood lactate Blood gases which can identify severe sepsis and respiratory failure

What tests are used to investigate how severe infection is?

Non-nucleotide reverse transcriptase inhibitors

What type of drugs are Efavirenz and Nevirapine?

Trichophyton rubrum

What typically causes Tinea pedis?

tinea rubrum

What typically causes tinea cruris?

Haemophilus influenza

What used to cause meningitis but does so less now the vaccination has been introduced?

• Microscopy, culture & sensitivity • Enteric viruses PCR (part of outbreak, immunosuppressed) • Ova, cysts & parasites (recent travel, immunosuppressed, symptoms >2 weeks) • C difficile screen

What would you test for in stool in gastroenteritis?

co-amoxiclav + clarithromycin

What would you treat high severity pneumonia with?

When there is a possible diagnosis of vasculitis (when immune system attacks blood vessels) • Symptoms of vasculitis overlap with symptoms such as SLE. • Can be used for a diagnosis of Granulomatosis with Polyangitis (formally known as Wegener's granulomatosis) - a type of vasculitis

When are anti-neutrophilic cytoplasmic antibodies ordered?

To QUICKLY and reliably achieve targeted serum antibiotic concentrations Some antibiotics are only available intravenously and are not well absorbed orally

When are antibiotics given IV?

When the antibiotic reaches systemic circulation

When are oral and IV antibiotics equal in the body?

If the patient has symptoms, If they test positive for dsDNA autoantibody Good specificty and good sensitvity But would need to monitor patient for kidney disease

When do you diagnose and start treatment for SLE?

Soap and water for visibly soiled hands and contact with particular infections e.g. C diff, viral gastroenteritis Hand washing on entry and exit

When do you wash your hands?

o Antibiotics should be started when the benefits of starting are greater than the disadvantages. o There are times when antibiotics should always be started e.g. patients with sepsis, and there are times when antibiotics should never be started e.g. patients with no evidence of infection e.g. auto-immune inflammation. o In-between, individual patient factors may mean antibiotics may or may not be started. o It can be reasonable not to start antibiotics in a patient with an infection, but this must be done within the context of an overall management plan e.g. a patient with a skin abscess may not be given antibiotics if there is a plan for surgical drainage of the abscess.

When should antibiotics be started?

• Guidelines suggest that antibiotic prophylaxis for SPB be given to the following patients: o Patients with cirrhosis and gastrointestinal bleeding. Antibiotic prophylaxis in this setting has been shown to decrease mortality in randomized trials. o Patients who have had one or more episodes of SBP. In such patients, recurrence rates of SBP within one year have been reported to be close to 70 percent. o Patients with cirrhosis and ascites if the ascitic fluid protein is <1.5 g/dL (15 g/L) along with either impaired renal function or liver failure. Impaired renal function is defined as a creatinine ≥1.2 mg/dL (106 micromol/L), a blood urea nitrogen level ≥25 mg/dL (8.9 mmol/L), or a serum sodium ≤130 mEq/L (130 mmol/L]). Liver failure is defined as a Child-Pugh score ≥9 and a bilirubin ≥3 mg/dL (51 micromol/L).

When should you give antibiotic prophylaxis for spontaneous bacterial peritonitis?

o Travel—inside or outside UK o Occupation—farmer, fishmonger, vet, air steward etc o Animal contact—which animal? What was the nature of contact? o Hobbies/past times o Sexual history

When symptoms suggest a diagnosis of infection, other information can help identify potential pathogens:

Intake Excretion or loss by the kidneys or gut Tissue redistrubution or storage

When there is a change in the level of a substance, what is this caused by? (3 things)

Signs and symptoms ? Pain, itchy, jaundice, Tired All The Time, bruising Lifestyle ? Alcohol, obesity, diabetes, recent travel, drug use Is liver disease present ? hepatitis, haemochromatosis, liver cancer, drugs What is the severity ? chronic hepatitis vs acute onset

When to measure LFTs

o Cases of food poisoning o Infectious bloody diarrhoea o Enteric fever (salmonella typhi or praratyphi) o Haemolytic Uraemic Syndrome (most common cause of acute kidney failure) o Food handlers

When to notify PHE about gastroenteritis symptoms

When there is a high risk of complications

When to use antivirals in acute infections in the general population

Helps to interpret microbiology culture results from samples E.g. ascitic fluid collected from the peritoneal cavity should normally be sterile, whereas faeces samples should normally have many bacteria culturable from it Knowing which bacteria are common at certain body sites helps you guess which bacteria cause infections in nearby body sites o E.g. urinary tract infections in women often result from faecal bacteria present in the nearby rectum o E coli bacteria is common in faeces therefore the UTI cause = E coli o The same is true of intra-abdominal infections when faeces contaminates the peritoneal cavity during colorectal surgery

Why is it important to know the sterile sites from the non-sterile sites in the body?

To choose empirial antibiotic therapy Can know likely antibiotic susceptibility

Why is it important to know which pathogens cause which infection?

leucodepletion

When whole blood is filtered before further processing to remove white blood cells. Removes greater than 99% of the leucocytes, reducing the risk of specific types of transfusion reactions and transmission of cytomegalovirus.

made in bone marrow, mature in thymus

Where are T cells made and where do they mature?

Originate in the soil (geophilic) Other animals (zoophilic) Or other humans (anthrophilic)

Where do dermatophytes originate from?

Pelvis Skull Spine Legs This is where new bone tissue gradually replaces old bone tissue

Where does Paget's disease of the bone most commonly affect?

60-70% occur in the head of the pancreas-->results in obstruction of the pancreatic duct 5-15% body of pancreas 10-15% tail 5-15% diffuse involvement • Highly invasive and elicits a "desmoplastic response" • Desmoplastic response: intense non-neoplastic host reaction composed of fibroblasts, lymphocytes and extracellular matrix The common bile duct also enters the head of the pancreas so a tumour in this would obstruct the common bile duct-->PAINLESS JAUNDICE

Where does pancreatic intraepithelial neoplasia occur?

Predominantly intracellular P in ATP Intracellular signalling Cellular metabolic processes e.g. glycolysis • Structural importance: Backbone of DNA o Component of hydroxyapatite Ca₁₀(PO₄)₆(OH)₂ o Membrane phospholipids o Deficiency of phosphate can cause weakness and dysfunction o Severe depletion can be fatal.

Where is phosphate PO43- found and what is it physiological importance?

hot, moist countries--Africa and Asia

Where is the distribution of malaria most common?

C type: Ciprofloxacin Cefuroxime Co-amoxiclav

Which antibiotics are most likely to cause C.diff infection?

Quinolones (ciprofloxacin) Metronidazole Anti-folates: Trimethoprim Sulfadrugs

Which antibiotics target DNA replication?

Rifamycin (rifampicin)

Which antibiotics target RNA synthesis?

Beta lactams: Penicillins (amoxicillin, pencillin IV) Cephalosporins (cefuroxime) Carbapanems (meropenem) Glycopeptides (e.g. vancomycin)

Which antibiotics target the cell wall of bacteria?

Tetracyclines (doxycycline) Macrolides (erythromycin) Chloramphenicol Aminoglycosides (gentamicin)

Which antibiotics target translation (protein synthesis)?

Clostridium

Which class of bacteria are spore forming?

Lamvidine and Tenofovir

Which drugs do you give in regimen, if there is a dual infection of hep B and HIV?

• HNPCC: DNA mismatch repair • FAMMM: p16/cdkn2a • Familial breast cancer: BRCA2 • Ataxia-telangiectasis: ATM • Von Hippel-Lindau: VHL • Familial pancreatitis: cationic trypsinogen, SPINK1 • Peutz-Jeghers: LKB1/ STK11

Which genes/cancer syndromes give an increased risk of pancreatic adenocarcinoma?

Cryptosporidium parvum and hominis MICROPARASITE-->sporozoan

Which parasite causes crytosporidosis

elderly and those on PPIs

Which patients are at higher risk of developing c.diff?

Vancomycin/teicoplanin (glycopeptides) Gentamicin (aminoglycosides) These are ototoxic (toxic to ear) and nephrotoxic drugs Efficacy of these drugs can be reduced if they are below therapeutic levels

Which specific drugs are therapeutically drug monitored?

non-specific

Which type of symptoms help to support the diagnosis of infection: specific or non-specific?

Parvovirus B19 (slapped cheek syndrome)

Which virus can trigger aplastic crisis (not producing RBCs) in patients with haemoglobinopathies?

- RNA viruses mutate more than DNA viruses so they are harder to treat - DNA viruses mutate less so they require less complex treatment - RNA viruses mutate more so will require more complex treatment

Which viruses RNA or DNA mutate more and become more resistant to antivirals?

Poor predicted value Patients suffering from non-thyroidal illness may show abnormalities within their thyroid function tests despite being euthyroid TSH levels may be suppressed in acute phases of illness

Why should you not measure TFT in unwell patients?

malabsorption syndrome (with bacteria-laden macrophages) & polyarthritis • Lymph system not working as well, common signs: weight loss, joint pains, diarrhoea should screen • Tropheryma whipplei, the agent of Whipple's disease, is ubiquitous (everywhere) in the environment • The bacterium has been detected in sewage and is more prevalent in the faecal samples of sewage workers (12-26 percent) than the general population • Disease mainly affects white males of European ancestry • Likely immune defect. Rare • Ubiquitous (everywhere) in the environment • UNCOMMON BUT TREATABLE • Classic Whipple's disease is a multi-systemic process characterized by joint symptoms, chronic diarrhoea, malabsorption, and weight loss • The disease presents over time, with joint symptoms preceding the others by many years, so not all symptoms may be manifest at the time of presentation in affected individuals • It should be considered in all patients with the four cardinal manifestations (arthralgias (pain in a joint), diarrhoea, abdominal pain, and weight loss) (joint and GI "pain") after more common conditions have been excluded. • Upper gastrointestinal endoscopy with biopsies of the small intestine is the diagnostic test of choice and PCR for the organism • Whipple's disease pathology in distal duodenum: white plaques representing engorged lymph vessels

Whipple's disease

Chronic neurological, hepatic, renal, pulmonary and chronic cardiac disease Diabetes mellitus Severe immunosuppression Age over 65 years Pregnancy (including up to two weeks post-partum) Children under 6 months of age Morbid obesity (BMI ≥40)

Who are high risk patients that should be treated for influenza?

In Western Europe and North America, there are clusters of cases associated with pigs, undercooked meat, especially pork Vast majority of cases are asymptomatic Fulminant (severe and sudden onset) hepatitis with a high mortality of 25% occurs in infected pregnant women

Who gets Hep E?

Associated with lower socioeconomic groups, returning tourists and men who have sex with men Infection in children, especially those under 5 usually are asymptomatic 50% infected adults are symptomatic

Who gets hep A? Who gets symptoms?

Athlete's foot is more common than onychomycosis and is more common in adults and sportsmen

Who is athlete's foot more common in?

Women Elderly

Who is autoimmunity more common in?

prepubertal children

Who is scalp ringworm (tinea colitis) most common in?

Treat patients with acyclovir in those over 60 years to reduce the incidence of a post herpetic neuralgia This involves the eye and affects the immunocompromised The older you are, the more likely you are to get reactivation of chicken pox into shingles

Who should especially be treated in patients with shingles and why?

Provides advice for individual cases or for clinical care protocols Support for clinical trials Bridges preclinical and clinical subjects

Why are diagnostics important?

Because high sensitivity and specificity rarely coexist Increased sensitivity is traded for decreased specificity and vice versa

Why are ideal tests rarely ever available in routine practice?

They support the diagnosis of infection Negative inflammatory markers make the diagnosis of infection less likely

Why are inflamamtory markers useful?

Less rejection episodes Better graft survival National kidney waiting lists Less sensitisation Establish relationships

Why do HLA typing?

• Those components of the immune system implicated in allergic responses are primarily involved in responses to parasitic infection. • The immune system has evolved to generate a rapid tissue-based response to re-infection. • The lack of infectious drive is a contributory factor in allergic disease.

Why do we get allergies?

o Prevent individual disease—lifelong, not just in children o Ideally, halt carriage and transmission-->herd immunity is a side effect o Ideally, eliminate-->eradicate the disease

Why immunise?

o Haemoglobin is not much help in infection—but anaemia of chronic disease (normocytic, normochromic) can be caused by infection o White blood cell count CAN be raised in infection, but other conditions too so it has poor specificity o Severe sepsis can LOWER white blood cell count

Why is a full blood count useful in diagnosing infection?

Key component of hydroxyapatite Ca₁₀(PO₄)₆(OH)₂ This is the predominant mineral in bone

Why is calcium structurally important in the bone?

o Protects individuals & communities from serious infections o Proactive measure for well people o Reflects NHS & professional quality o Long history, a busy present, a big future

Why is immunisation important?

Effects of pleural fibrosis

Widespread thick fibrosis can prevent normal expansion and compression of the lung during respiration causing breathlessness Fibrous adhesions can wholly or partly obliterate the pleural cavity Removal of the fibrous tissue (pleural decortication) can improve the expansion and compression of the lung during respiration

• Inborn error of copper metabolism • Rarer genetic disease, wide range of alterations to the gene • Causes little caeruloplasmin: the copper transport protein in the blood • Patients have low serum copper, high urinary copper (24hr urine collection) and high levels of copper in the liver tissue • Copper accumulates in: o Liver: cirrhosis o Eyes: Kayser-Fleischer rings - Copper deposited in the eye can be seen as a ring around the iris by slit lamp investigation o Brain: ataxia • Some liver biopsy can be sent to measure the amount of copper in grams per dry weight of liver tissue • Some patients present with acute liver failure and haemolysis = life threatening and an indication for super-urgent liver transplantation • Treatment: to chelate copper and enhance its excretion • Rhodamine stain: copper = brown

Wilson disease

How is a pregnant woman identified for bacteriuria?

Women should be offered routine screening for asymptomatic bacteriuria by midstream urine culture early in pregnancy. Identification and treatment of asymptomatic bacteriuria reduces the risk of pyelonephritis

Which pregnant women are offered intrapartum prophylaxis for group B streptococci? I.e. preventative medication during pregnancy

Women with a previous baby with neonatal Guillian Barre Syndrome disease Women with GBS in current pregnancy Women who are pyrexial in labour should be offered broad-spectrum antibiotics including an antibiotic for prevention of neonatal EOGBS disease

agammaglobulinaemia

X-linked condition associated with a lack of antibodies in the bloodstream?

Which children are most susceptible to infection?

Young infants Children with special health care needs Children with impaired immune systems Children with long standing prosthetic devices Good news As children age, the incidence of illness decreases from 12 per year to 4 per year by the time the child is 5 years old 90% of infections are mild, self-limited, and require no treatment

The zone where bacteria can't grow around a given antibiotic. This is usually related to the level of antimicrobial activity in the sample, a larger zone of inhibition mean that the antimicrobial is more potent

Zone of inhibition

Human papillomaviruses

a virus that causes genital warts and cervical cancer Double stranded DNA viruses 7.9kb circular genome, 7 'early genes', 2 'late' genes >100 subtypes, based on DNA sequence Different types affect different tissues Life cycle linked to epithelial differentiation Genital HPVs = low and high oncogenic risk In most women, HPV causes no long term harm and is cleared by the immune system High risk HPVs are also involved in penile intraepithelial neoplasia and squamous cell carcinoma. They are also involved in a subgroup of oral squamous cell carcinomas, which have become more common in recent years. Interestingly smoking is important in the aetiology of cervical cancer. Smoking is known to decrease to numbers of antigen presenting cells in cervical epithelium and may effectively cause local Immunosuppression.

• Flat adenomas • Size most malignant polyps >10mm • Villous and tubule-villous • Severe: high grade dysplasia • Lynch syndrome associated adenomas: genetic condition

adenomas become malignant when there are

Dysplasia

abnormal development or growth of cells, tissues, or organs Earliest morphological manifestation of multistage process of neoplasia Cytological features of malignancy, but no invasion (= in-situ disease) Removal is curative; if left, significant chance of developing invasive malignancy - Elimination of abnormal cells = removes chance of cancer developing - CIN I to CIN III = basaloid cells: more purple = become more prevalent and further up epithelium - CNIII: full thickness spread across epithelium, carcinoma in situ - Whole basis of cervical screening programme

What is lymphocytosis and when does it occur?

abnormal increase in lymphocytes There are atypical lymphocytes in glandular fever (infectious mononucleosis) and chronic lymphocytic leukaemia

Oral-->slower absorption IV-->faster/instantaneous absorption

absorption of oral vs IV antibiotics

enlargement of the extremities

acromegaly

Define endometritis

acute or chronic inflammation of the endometrium usually due to infection

• Skin graft onto green mouse = okay and fine from green e.g. identical twin on another = no rejection • Skin graft from green to an orange gets rejected in 10 days, lots of WBCs • Green one back on second one = second set, gets rejected quicker = memory so immune response accelerated • Accelerated memory response: transfer this memory with lymphocytes • Surface on green that is seen by foreign by orange • Just knew it was genetic but not why

adoptively acquired immunity

o Single dose often sufficient to induce long-lasting immunity o Strong immune response evoked o Local and systemic immunity produced

advantages of live vaccines

Sickle cell anaemia

an autosomal recessive anaemia due to substitution of a single amino acid (valine for glutamic acid) characterized by red blood cell becoming sickle-shaped and non-functional.

Reduced red blood cells

anaemia

a form of rheumatoid arthritis that primarily causes inflammation of the joints between the vertebrae HLA allele B27, if have then 87.4 more times likely to get the disease

ankylosing spondylitis HLA molecule

A system of informatics, data collection, personnel, and policy/procedures which promotes the optimal selection, dosing, and duration of therapy for antimicrobial agents throughout the course of their use

antibiotic stewardship

terbinafine

antifungal use to treat athlete's foot

disinfection applied to damaged skin or living tissues-->requires a disinfectant with minimal toxicity

antisepsis

Sore throat

any of various inflammations of the tonsils, pharynx, or larynx characterized by pain in swallowing Viral (70-80%) Group A beta-haemolytic Streptococcus (20-30%)

reaction to inhaling aspergillus o Space occupying/non-invasive aspergillosis occurs in the lung cavity-->e.g. aspergilloma (fungal ball) o Allergic reaction—asthma, cystic fibrosis-->e.g. allergic bronchopulmonary aspergillosis, allergic sinus disease o Chronic infection—chronic lung disease-->chronic pulmonary aspergillosis o Invasive infection—immunocompromised (leukaemia)-->e.g. invasive pulmonary aspergillosis, invasive aspergillus sinusitis

aspergillosis

Fungus that causes an allergic reaction and can present as asthma

aspergillus

genetic tendency to develop allergy

atopy

Scl-70

autoantibody in diffuse systemic sclerosis

cells respond to signaling substances that they themselves secrete

autocrine signaling

Help with immunoological problems, help fight pathogens

benefits of HLA molecule

Define leiomyomata

benign smooth muscle umours of the myometrium

Penicillin (amoxicillin)➡cephalosporins (cefuroxime)➡carbapenems (meropenem) Narrow➡broad

beta lactam spectrum of activity

Ludwig's angina

bilateral infection of submandibular space

osteoblasts

bone forming cells

• Pain • Often worse at night and gets better with movement initially • Usually becomes constant • Broken bones Pathological fractures: • Commonly femur, humerus, vertebrae • Numbness, paralysis, trouble urinating • Spinal cord compression from bone metastases • Loss of appetite, nausea, thirst, confusion, fatigue • Symptoms of hypercalcaemia • Anaemia • Disruption of bone marrow

bone metastases presenting symptoms

osteoclasts

bone resorbing cells

abnormal dilation of the bronchi with accumulation of mucus

bronchiectasis

indicates amount of endogenous insulin formed

c peptide

malignant neoplasm that has the potential to spread

cancer

Tumours - Non-secretory adenoma, metastatic carcinoma Trauma Infarction Inflammation - granulomatous, autoimmune, other infections Iatrogenic

causes of anterior pituitary hypofunction

o Mixture of sensitive and resistant bacterial strains exposed to antibiotics o Sensitive strains will die out o Resistant strain will become dominant colonising strains o Subsequent endogenous infection is more likely to be caused by antibiotic-resistant strains o Antibiotic-resistant strains may be transferred to other people

causes of antibiotic resistance

mainly CKD or vitamin D deficiency

causes of secondary hyperparathyroidism

B-lymphocyte antigen CD20 or CD20 is an activated-glycosylated phosphoprotein expressed on the surface of all B-cells

cd20

what can cervical glandular intraepithelial neoplasia progress to?

cervical adenocarcinoma

liver tumour that arises in bile ducts

cholangiocarcinoma

gall bladder

cholecystitis occurs when there is an infection of

stoppage of bile flow Disorders of the liver, bile duct, or pancreas can cause cholestasis. The skin and whites of the eyes look yellow, the skin itches, urine is dark, and stools may become light-colored and smell foul.

cholestasis

sarcoidosis

chronic inflammatory disease in which small nodules (granulomas) develop in lungs, lymph nodes, and other organs

permanent, destructive pulmonary disorder that is a combination of chronic bronchitis and emphysema

chronic obstructive pulmonary disease (COPD)

HLA molecule, beta at bottom and two alpha helices, antigen sits in between • Class 1 process peptides from intracellular organisms: more important in fighting intracellular organisms e.g. fungi and viruses

class 1 molecule

more selectively expressed, heterodimers: alpha and beta (part of each and two peptides by each one of the chains • Class 2: protein peptides that have been broken down by cells: defend against pathogens

class 2 molecule

clostridium perfringens

classical cause of gas gangrene

Flagella Amoeboids Sporozoans Trypanosomes

classification of parasites protozoa

jaundice

clinical effect of hyperbilirubinaemia

• local effects of tumour • distant metastases • non-specific features • asymptomatic, discovered incidentally

clinical features of asbestos

• Parasites rupture red blood cells, block capillaries and cause an inflammatory reaction • Fever and rigors (alt. days with falciparum malaria, every 48hrs or 72hrs with benign malaria) • Cerebral malaria (confusion, headache, coma) • Renal failure (black water fever) • Hypoglycaemia • Pulmonary oedema • Circulatory collapse • Anaemia, bleeding and DIC (disseminated intravascular coagulation)

clinical manifestations of malaria

insulinoma

common pancreatic neuroendocrine tumour that can result in hypoglycaemia

spider naevi

common sign of chronic liver disease

Define PCOS

common, multiple follicular cysts, hyperandrogenism, menstrual irregularity

streptococcus pneumoniae

commonest cause of penumonia

bronchiolitis

condition seen in infants that results in inflammation, oedema of the bronchioles and is commonly caused by respiratory syncytial virus

Barrett's oesophagus

condition where squamous mucosa of oesophagus is replaced by columnar mucosa

Common benign neoplasm of the genitals caused by viral infection

condyloma acuminatum

abnormal enlargement of the right side of the heart as a result of disease of the lungs or the pulmonary blood vessels.

cor pulmonale

Cystitis

cytotoxic side effect of cyclophosphamide

recurrent sinopulmonary infection

deficiency in antibodies causes

SCID

deficiency in t cells causes

Sensitivity

defined as the proportion of abnormal results correctly classified by the test expresses the ability to detect a true abnormality Sensitivity = TP / ( TP+FN )

Specificity

defined as the proportion of normal results correctly classified by the test expresses the ability to exclude an abnormal result in a healthy person Specificity = TN / (TN+FP)

Flucloxacillin is normally used to treat staph aureus infections by binding to the penicillin binding protein MRSA has a mutation in the penicillin binding protein so is resistant to flucloxacillin

describe MRSA

Relative incidence: 1 Age distribution: increases with age Acid levels: normal or low H.pylori gastritis causes a gastric ulcer 70% of the time Gastric ulcers are localised to the lesser curve of the stomach, antrum-corpus junction, prepyloric MAINLY AFFECTS BLOOD GROUP A PATIENTS

describe gastric ulcers

o Vancomycin, teicoplanin o Large molecules, bind directly to terminal D-alanyl-D-alanine on NAM pentapeptides o Inhibit binding of transpeptidases and thus peptidoglycan cross-linking o Gram-positive activity o Unable to penetrate Gram-negative outer membrane porins

describe glycopeptides

Single layer of peptidoglycan Washes out first blue/black stain so stains red

describe gram negative bacteria

thick cell wall consisting of several layers of peptidoglycan stains blue/black

describe gram positive bacteria

o Commonest cause of bacterial pneumonia o Commonest cause of bacterial meningitis (except in neonates) o Can also cause other childhood infections such as otitis media (middle ear infection)

describe streptococcus pneumoniae

Can be referred to as group A strep Commonest cause of bacterial sore throat Also causes: -Scarlet fever -Necrotising fascitis SSTIs Invasive infection such as pneumonia Puerperal sepsis Also associated with secondary immunological presentations such as glomerulonephritis

describe streptococcus pyogenes

If secondary is left too long untreated Calcium is usually high PTH is inappropriately high Phosphate can be high or low

describe tertiary hyperparathyroidism

composed of cortical bone and is also called compact bone • The hard outer layer gives bone its smooth, white and solid appearance and accounts for 80% of the total bone mass of an adult skeleton • Cortical bone consists of multiple microscopic columns, each called an osteon. Each column is multiple layers of osteoblasts and osteocytes around a central canal called the Haversian canal. • Volkmann's canals at right angles connect the osteons together. • The columns are metabolically active, and as bone is reabsorbed and created the nature and location of the cells within the osteon will change. Cortical bone is covered by aperiosteum on its outer surface, and an endosteum on its inner surface.

describe the hard outer layer of bone

Group of disorders characterised by hyperglycaemia which is caused by a lack of insulin or reduced action of insulin

diabetes

This is different from normal diabetes diagnosis o Oral glucose tolerance test (but criteria is different from normal diabetes) o If there was previous gestational diabetes—could ask to use self monitoring using capillary blood glucose o DO NOT USE HbA1c

diagnosis of gestational diabetes

Heaf test

diagnostic skin test to determine exposure to mycobacterium tuberculosis (intradermal injection of tuberculin)

Pathological manifestations are largely confined to the CNS Produce spongiform change in brain tissue on histology Long incubation times (up to 30 years i.e. time between exposure to pathogen and first appearance of symptoms) progressive and fatal

human prion diseases share certain properties:

removal or destruction of sufficient numbers of potentially harmful microorganisms to make them safe to use Disinfection is achieved by the use of chemical disinfectants

disinfection

Bone 54% Intracellular 45% Extracellular 1%

distrubution of magnesium in the body

steroids-->normally high dose and prolonged Atypical anti-psychotics Immunotherapy e.g. nivolumab used in melanoma treatment Protease inhibitor (used in HIV treatment)

drugs which can induce diabetes (drug induced diabetes)

presence of normal endometrium in an abnormal locaton

ectopic endometrium Endometriosis

increases glucose production decreases glucose utilisation increases lipolysis

effect of adrenaline on glucose production, glucose utilisation and lipolysis

• latent period is about 20yrs between exposure and development of carcinoma • in combination with cig smoking the risk is increased (20-100 fold) • associated with other respiratory illness, lung fibrosis and mesothelioma (malignant tumour of the pleura) • usually more than one exposure and over a long amount of time e.g. Turkey (high incidence, due to brought up with asbestos everywhere as use it for the white wash of houses therefore high death rate • sticks to the lungs, needle shape under microscope, cannot see

effect of asbestos on lung cancer

Increases glucose production, decreases glucose utilisation and increases lipolysis

effect of cortisol on glucose production, glucose utilisation and lipolysis

Increases glucose production Decreases glucose utilisation

effect of free fatty acids on glucose production and glucose utilisation

increases

effect of glucagon on glucose production

increases growth hormone decreases glucose utilisation increases lipolysis

effect of growth hormone on glucose production, glucose utilisation and lipolysis

glucose production--decrease glucose utilisation--increase lipolysis--decrease

effect of insulin on glucose production, glucose utilisation and lipolysis

the more proteins bound to calcium, the lower the total calcium

effects of changes in binding proteins on calcium

Risk factors of a transfusion associated circulatory overload

elderly patients small children patients with compromised left ventricular function large transfusion volume increased rate of transfusion Prevention: follow guidance on volume and rate of transfusion for each component

Subclinical hypothyroidism

elevated TSH, normal T4

Enlarged alveolar spaces

emphysema

Specialized cells release hormone molecules into vessels of the circulatory system, by which they travel to target cells in other parts of the body.

endocrine signaling

Endometriosis

endometrial tissue located outside the uterus Ectopic endometrium (regurgitation theory/metaplasia theory/stem cell theory/metastasis theory-->bleeding into tissues-->fibrosis 6-10% of women, 30 - 40yo Hx: 25% asymptomatic, dysmenorrhoea (painful periods), dyspareunia (painful sexual intercourse), pelvic pain, subfertility (less than nornally fertile), pain on passing stool, dysuria Ix: Laparoscopy Rx: Medical (COCP, GnRH agonists/antagonists, progesterone antagonists) or surgical (ablation/ TAH-BSO) Links: Ectopic pregnancy, ovarian cancer, IBD

caeruloplasmin

enzyme that can be tested for in the blood to help with the diagnosis of Wilson's disease

inflammation of the testicles and epididymis • 2 main aetiologies: Enteric/UTI or STI • Urine- sent for cultures • Urine- sent for Chlamydia and Gonorrhoea NAAT (PCR) • If Severe: Bloods, blood cultures, USS +/- drainage

epididymo-orchitis

Alendronate Risedronate Ibandronate IV zoledronic acid

examples of bisphosophonates

IL-1 IL-6 TNF

examples of cytokines

triad of symptoms in infectious mononucleosis

fever tonsillar pharyngitis cervical lymphadenopathy with a positive monospot test

Fibrocystic changes of the breast

formerly called fibrocystic disease, this benign condition affects the glandular and stromal tissue. The changes may take a variety of forms with typical symptoms of cysts, lumpiness, and/or pain. Generally affects pre-menopausal women. Usually B/L and multifocal. Autopsy series : FCC in approx. 60% of normal breasts. Risk of Fibrocystic Change development is increased in women with hyperoestrogenism. No increased risk for subsequent carcinoma development.

fracture caused by injury that would normally be insufficent to cause fracture to a normal bone i.e. is caused by minimal trauma like falling from a standing height

fragility fracture

candida

fungus responsible for oral thrush

• Lifelong nutritional supplements • Early use of nutritional support in acute illness

general CF treatments

Aminoglycoside; protein synthesis inhibitor

gentamicin

a form of diabetes mellitus that occurs during some pregnancies that was not present prior to the pregnancy o Hyperglycaemia is first detected in pregnancy o Gestational diabetes is defined as having a fasting glucose above 5.6 mmol/litre (usually 7mmol/l in non-pregnant) OR 2 hour plasma glucose level of 7.8mmol/litre (usually 11.1mmol/l in non-pregnant)

gestational diabetes

polypeptide made up of 29 amino acids Rapidly degraded in the tissues especially the liver and kidney

glucagon

iron storage disorder which can result in diabetes

haemochromatosis

TSH secreting tumour or thyroid hormone resistance

high TSH, high T4

primary hypothyroidism

high TSH, low T4

an organism which harbours the parasite

host

Factors that are unique to a particular patient that affect the patient's susceptibility to infection and response to various antibiotic drugs. Examples include a low neutrophil count or a lack of immunoglobulins in the blood that carry antibodies.

host factors

light microscopy (histology)

how are primary lung carcinomas classified?

Hand hygiene Environmental cleaning Decontamination

how do you remove the reservoir in infection control?

get a sputum sample

how do you test if a chest infection is bacterial?

MRSA produce a cell membrane molecule that beta lactam antibiotics can't bind to, making the antibiotics ineffective So, MRSA is resistant to most beta lactam antibiotics

how does MRSA work?

PTH modulates renal maagnesium reabsorption in the distal convoluted tubule

how does PTH regulate magnesium homeostasis?

hormone can only have an influence over a cell that has specific target receptors for it

how does a hormone influence a cell?

lowers NAD which is needed for gluconeogenesis

how does alcohol cause hypoglycaemia?

Insulin activates mitogens which stimulates blood vessels to proliferate and this results in an increased risk of atherosclerosis

how does insulin cause vascular fibrinolysis?

Based on the normal or reference range which defines the values of a biochemical test found in healthy subjects against which patient values can be compared However, this is an artificial concept and no clear boundaries exist

how is abnormal biochemistry identified?

osteoblasts are constantly producing and secreting matrix which help with mineralisation

how is bone a dynamic tissue?

thyroid surgery

how is the recurrent laryngeal nerve commonly damaged?

activated by the liver and kidney after sun light exposure

how is vitamin D activated?

over the previous 8-12 weeks

how long does HbA1c reflect average plasma glucose?

Every 1-2 months after radioactive iodine and if the patient remains thyrotoxic then biochemical monitoring continues at 4-6 week intervals OR Following a thyroidectomy for Graves' disease, serum TSH to be measured 6-8 weeks post op

how often should you repeat TFTs in those with hyperthyroidism (Graves)?

every 3 years

how often should you repeat a TFT in a healthy person?

o use clinical guidelines o switch from IV to PO antibiotics o antibiotic restriction o microbiologist support o education o use of biomarkers o audit and feedback

how to implement antibiotic stewardship

macrophages to attack

if a bacteria is covered in complement, what does this make more likely?

every 1 year

if higher risk colitis, how often do you see them?

every 3 years

if intermediate risk colitis, how often do you see them?

every 5 years

if low risk colitis, how often do you see them?

biochemical test that uses the reaction of an antibody to its antigen to measure the amount of a substance in a liquid

immunoassay

Enhancement of immune responseThis occurs through: Immunisation-->either active or passive Replacement therapies Immune stimulants

immunopotentiation

Requires use of alternatives which may be: Expensive E.g. linezolid, tigecycline, daptomycin instead of flucloxacillin to treat MRSA Toxic: E.g. colistin used instead of meropenem for carbopenemase producing enterobacteriacae (CPE) Last line antibiotics: E.g. meropenem is prescribed instead of ciprofloxacin for multi-resistant enterobacteriacae

implications of antibiotic use in targeted therapy

Advanced malignant mesothelioma image

in dark blue

in health, 50% of Alkaline phosphatase is in the bone and 50% is in the liver

in health what proportionof alakaline phosphatase is where?

ingestion of a bacteria, virus or parasite

infection

Pupural endometritis

infection of the womb during puerperium affects ~5% of pregnancies Puerperal sepsis remains a major cause of maternal death Risk factors include caesarean section, prolonged labour, prolonged rupture of membranes, multiple vaginal examinations

1) Metabolic 2) Paracrine 3) Vascular fibrinolysis: growth and cancer

insulin has three types of effect

a benign tumor of the pancreas that causes hypoglycemia by secreting additional insulin

insulinoma

otixicity with frusemide

interaction of aminoglycosides

enhances the anticoagulant effect increases plasma phenytoin concentrations increase plasma digoxin concentrations

interaction of macrolides e.g. clarithromycin

refers to a group of almost 200 disorders that cause inflammation and scarring of the alveoli and their supporting structures Very heterogenous group Usually diffuse and chronic Diseases of pulmonary connective tissue Mainly alveolar walls Restrictive rather than obstructive lung disease Causes often unknown Increased tissue in alveolar-capillary wall Inflammation & fibrosis Limited morphological patterns that differ with site and with time in any individual but with many causes & clinical associations Decreased lung compliance Increased gas diffusion distance

interstitial lung disease

ingestion of a preformed toxin

intoxication

o Gross Structure-->X-ray o Bone Mass (Calcium)-->DEXA o Cellular Function / Turnover-->Biochemistry o Microstructure / Cellular Function-->Biopsy, qCT

investigation of bone disease

• Blood Cultures • Bloods: FBC, U&E's, LFTs, Clotting, amylase • Imaging: CT

investigations for diverticulitis

yes

is cellular rejection reversible?

When two different enzymes, which may be different in their composition, act as catalysts for the same reaction, or set of reactions.

isoenzyme

Nucleoside reverse transcriptase inhibitor Cytosine analogue Used in the treatment of HIV

lamivudine

Epidermis (top layer)--stratified squamous epithelium Dermis Subcutis

layers of the skin

transmission-mode of transmission from the source to the host Susceptible host i.e. non immune

life cycle of a pathogen

stratified squamous

lining of mucosa in oesophagus

alkaline phosphatase

liver enzyme commonly elevated in cholestasis

Define endometrial polyps

local endometrial overgrowth

Hypoparathyroidism

low PTH, low calcium

primary hyperthyroidism

low TSH, high T4

term given to tumour spread through the lymphatics of the lung and is most commonly seen secondary to adenocarcinoma.

lymphangitis carcinomatosa

normal or low

lymphocytes in bacterial infection

raised

lymphocytes in viral infection

Cervical carcinoma

malignant tumor of the cervix Revise the patterns of spread of malignant tumours and consider which are likely to be most important in cervical cancer. (1) local invasion, extending out of the cervix to bladder, ureters and rectum. This may make primary surgical treatment inappropriate. (2) Lymphatic metastasis. The tumour spreads to local lymph nodes This dictates treatment: surgery involves radical hysterectomy with pelvic and para-aortic lymph node dissections. Radiotherapy also takes in lymph node fields. (3) Haematogenous spread NB early lesions may not need radical surgery and can be cured by LLETZ: stage IA1 has a depth of invasion of <3mm and maximum lateral dimension of <7mm. Stage IA2 has a depth of invasion of 3-5mm and maximum lateral dimension of <7mm.

mesothelioma

malignant tumour of pleura

a germ cell tumours of the ovaries with epithelial elements like skin, hair, teeth

mature teratoma

drug given for diabetic patients that is also used in polycystic ovarian disease

metformin

Helicobacter pylori

microorganism commonly associated with chronic gastritis

Streptococcus pneumoniae

most common cause of community acquired pneumonia

insulin administration due to diabetes

most common cause of hypoglycaemia?

Autoimmune Graves' disease

most common cause of primary hyperthyroidism

staphylococcus aureus

most common cause of skin infection

liver

most common sites for bowel cancer to metastasise

insulinoma

most common tumour in islet of Langerhans

papillary

most common tumour of the thyroid

Serous cystadenocarcinoma

most common type of ovarian carcinoma; may be bilateral with multilocular cysts

inflammation of muscle tissue

myositis

Amoxicillin Amoxicillin-clavulanic acid (Augmentin) Flucloxacillin Piperacillin-tazobactam (tazocin)

name some penicillins

A rapidly spreading destructive infection of the subcutaneous fat and superficial fascia. May be caused by one or multiple organisms. Streptococcus pyogenes is one of the most frequently isolated organisms

necrotising fascitis

adenoma

neoplastic cells on surface

cancer, which has surrounded and gained access to the vessels e.g. the vein so has the potential to spread around the body

neoplastic cells spread into submucosa

raised

neutrophils in bacterial infection

normal

neutrophils in viral infection

Closed pneumothorax

no associated external wound. A lung perforation, usually not traumatic, connects the lung air spaces to the pleural cavity Lung air is drawn into the pleural cavity during inspiration, reducing potential lung expansion

measles rubella parvovirus adenovirus human herpes virus 6 (HHV6)

non-vesicular rashes examples

CURB 65

o Confusion of new onset (defined as an AMTS of 8 or less) o Blood Urea nitrogen greater than 7 mmol/l (19 mg/dL) o Respiratory rate of 30 breaths per minute or greater o Blood pressure less than 90 mmHg systolic or diastolic blood pressure 60 mmHg or less o Age 65 or older

which nuclear receptor is commonly assessed in breast cancers by immunohistochemistry to decide treatment

oestrogen receptor

Define endometrial hyperplasia

oestrogenic stimulation of endometrial proliferation, continuous stimulation may lead to atypical hyperplasia and carcinoma

bone forming cells o Terminally differentiated products of mesenchymal stem cells. o Make osteoid (non-mineralised organic matrix, consists of mainly Type 1 collagen) o Communicate with other bone cells o Make hormones (e.g. osteocalcin), matrix proteins and alkaline phosphatase o Prerequisite for mineralisation o Osteoblasts that are buried/trapped within the matrix are called osteocytes

osteoblasts

break down bone to release minerals o Large. o Multinucleated o Ruffled-resorption border o Break down bone - critical for repair and maintenance of bone o Found in bone pits (resorption bays) o Produce enzymes such as tartrate-resistant acid phosphatase (TRAP) and Cathepsin K - secreted to breakdown extracellular matrix o Help enhance blood calcium levels o Regulated by hormones including PTH, calcitonin and IL-6 o RANK ligand and osteoprotegrin help with osteoclastic maturation and activity

osteoclasts

a bone cell, formed when an osteoblast becomes embedded in the matrix it has secreted. MATURE BONE CELL o Star shaped o Trapped/buried osteoblasts IN THE MATRIX o Communicate with each other via cytoplasmic extensions o Mechanosensory properties o Involved with regulating bone matrix turnover

osteocytes

thinner than average bone density (precursor to osteoporosis)

osteopenia

A condition in which the body's bones become weak and break easily. o Generalised loss of bone with propensity to fractures—spine, hip o Several common risk factors for bone loss o No abnormalities are seen in routine biochemical tests perhaps because they are too insensitive o Diagnosis relies on DEXA/x-ray o Increasing use of bone markers in management

osteoporosis

Signal released from a cell has an effect on neighboring cells.

paracrine signaling

Immunity conferred by transferring antibodies from an individual who is immune to a pathogen to another individual. E.g. transfers from mother to unborn baby-->"Maternal antibodies" can protect the baby for up to a year against illnesses to which the mother is immune. o This type of passive immunity, although effective, usually disappears within several weeks or months. o Most types of transfused blood contain antibodies

passive immunity

catecholamine secreting tumour arising from the adrenal medulla

phaeochromocytoma

• Total body phosphorus 23mol-700g o Bone 85% o Intracellular 14% o Extracellular 1%-->Phosphorus in the blood

phosphorus distribution in the body

Relative polycythaemia

plasma volume is reduced

Immunosuppresion HIV IV drug use Endocarditis

predisposiitons to getting brain abscesses

define gonadal failure

primary (ovarian) and secondary (hypothalamus/pituitary)

small infectious particle containing protein and no nucleic acid

prion

PTH is secreted but very low serum concentrations induce a paradoxical block In severely hypomagnesia patients, this block leads to clinically relevant hypercalcaemia

what do low levels of magnesium stimulate the Parathyroid to do?

Gene mutation leads to changes in the folding pattern of a protein As a result, the prion becomes resistant to the protease enzyme The prion therefore accumulates abnormally in the cell

prion proteins exist naturally in cells but it can also occur when:

microparasite

protozoa

o Structural support for the body o Protection of vital organs o Blood cell production (via marrow) o Storage bank for minerals (especially calcium)

purpose of bone

Endocrine: -Early menopause -Amenorrhoea in pre-menopausal women -Hypogonadism -Hormone ablation for breast/prostate cancer -Hyperparathyroidism -Cushing's -Hyperprolcatinaemia -Diabetes Gastrointestinal: -Coleiac disease -IBD -Chronic liver disease -Any cause of malabsorption Rheumatological: -Rheumatoid arthritis and other inflammatory arthropathies Haemtaological: -Myeloma -Haemoglobinopathies -Systemic mastocytosis Respiratory: -COPD -Cystic fibrosis Metabolic: -Homocystinuria-->absence of amino acid methionine Drugs: -Steroids (prednisolone > 7.5mgs daily for more than 3 months) -Heparin -Ciclosporin -Anti-convulsants Others: -Immobility -CKD

secondary causes of hyperthyroidism

normal TSH and low free T4 levels

secondary hypothyroidism

o A temperature above 38 o A heart rate above 90 o A respiratory rate above 20 o A white blood cell count above 12

sepsis can give a systemic inflammatory response syndrome and this is determined if you have 2 of the following:

a change in serologic tests from negative to positive as antibodies develop in reaction to an infection or vaccine

seroconversion

cholestatic jaundice

side effect of amoxicillin-clavulanic acid

otoxicity and nephrotoxicity Red man syndrome (vancomycin)-->allergic reaction which is a rash all over the body

side effect of glycopeptides

diarrhoea

side effect of macrolides e.g. clarithromycin

allergic reaction

side effect of penicillin

tendonitis prolonged QT interval

side effect of quinolones e.g. ciprofloxacin

C. diff infection-->antibiotic associated diarrhoea

side effects of all anitbiotics

ototoxicity (toxic to ear) and nephrotoxicity

side effects of aminoglycosides

OPTIC NEUROPATHY BLOOD DISORDERS

side effects of linezolid

Endometrial polyps

small nodules of hyperplastic endometrial tissue linked to infertility Sessile/polypoid E2-dependent uterine overgrowths More than 10% of women are affected in their 40-50s History--often asymptomatic, intermenstrual/post menopausal bleeding, mennorhagia (heavy menstrual bleeding), dysmenorrhoea Investigations-ultrasound, hysteroscopy Treatment-expectant, medical e.g. GnRG agonists, surgical Prognosis-more than 1% are malignant

organism commonly responsible for puerperal matitis

staphylococcus aureus

fatty change associated with inflammation in the liver

steatohepatitits

complete killing or removal of all types of microorganisms like bacteria, viruses, fungi and mycobacteria

sterilisation

Typical cause of community acquired pneumonia

streptococcus pneumoniae

• intermittent abdo pain, back pain and weight loss • fibrosis of exocrine tissue: can mimic carcinoma macroscopically and microscopically

symptoms of chronic abdominal pain

combination of two drugs causes an effect that is greater than the sum of the individual effects of each drug alone

synergism

osteoporosis

t score -2.5 and below

osteopenia

t score between -1 and -2.5

Progressive build up of air in the pleural space which allows air INTO the pleural space but not OUT of

tension pneumothorax

• Hepatocellular damage • Biliary tract damage • Imaging, biopsy

tests of liver damage

CCP

the autoantibody in: rheumatoid arthritis

Asbestosis

the form of pneumoconiosis caused by asbestos particles in the lungs Asbestosis is a usual interstitial pneumonia-like progressive pulmonary interstitial fibrosis caused by high level exposure to asbestos dust Fibrosis of the alveolar walls impairs both gas exchange and lung expansion and contraction during breathing Asbestosis associated with any occupation working with asbestos is a UK Government Prescribed Occupational Disease that is eligible for Industrial Injuries Disablement Benefit 431 registered deaths in 2014, 985 new Industrial Injuries Disablement Benefit cases in 2014. 1175 new Industrial Injuries Disablement Benefit cases in 2015

depends on the situation

there are various decontamination methods, how do you know which one to use?

2 types of pleural effusion

transudate and exudate

Flucloxacillin

treatment of cellulitis

o Tumour very small, early stage can remove by local excision technique by injecting fluid underneath the lesion and then dissect away, then send off to pathologist, remove tumour with normal rim round to make sure clear margin o Results will come back and if not advanced then will be only treatment they need = cure o More advanced, local or lymph nodes = surgeons do a more radical procedure = full or partial removal of stomach, gastrectomy o Partial or full gastrectomy depends on the site of the tumour o Tumour in gastric fundus or Gastro-oesophageal junction then can do partial by transecting the oesophagus and stomach o Down by the gastric antrum then will do a transection of the gastro-duodenal junction = partial o If tumour has spread outside the operative field, often the cause wit gastric cancer = chemotherapy, to reduce the chances of tumour occurring systemically

treatment of gastric cancer

debridement where you cut away as much as the infection as possible and treat with broad spectrum antibiotics like meropenem and clindamycin

treatment of necrotising fascitis

Key prognostic factors of a tumour

tumour grade tumour size nodal status

giardia and cryptosporidium

two most common parasites

type of endometrial tumour commonly seen in postmenopausal women and associated with endometrial atrophy

type 2 Serous carcinoma

Superficial Subcutaneous Systemic

types of fungal disease

identifying if organisms are clonally related

typing

rotavirus

virus commonly responsible for diarrhoea in infants and children

Extended spectrum beta lactamases, which have resistance to a wider range of β-lactams. • ESBLs are able to enzymatically break down many beta-lactam antibiotics including pencillins, amoxicillin and cephalosprins. • Some beta-lactam antibiotics are "stable" (not broken down) in the presence of ESBLs

what are ESBLs?

Thrombophlebitis (inflammation of a vein) Thrombosis Infection

what are IV access side effects of giving antibiotics IV?

o Enzymes that hydrolyse (inactivate) β-lactams o Common mechanism of resistance to β-lactam antibiotics o Different β-lactamase enzymes confer resistance to a narrow or wide range of β-lactams eg: - Staphylococcal β-lactamase - some penicillins only - 'Extended spectrum β-lactamase' (ESBL) - penicillins and cephalosporins - Carbapenemases (eg NDM1) - carbapenems

what are beta lactamase enzymes?

o Collagen related markers are based primarily on type I collagen which is widely distributed in several tissues o Changes in bone markers are not disease specific i.e. do not tell you what condition you have but reflect alterations in skeletal metabolism o Some markers are characterised by significant intraindividual variability

what are bone markers?

Oppose the action of insulin Cortisol, Glucagon, Growth hormone, epinephrine (adrenaline)

what are counter regulatory hormones?

matrix which helps with mineralisation

what are osteoblasts constantly producing and secreting?

Protein synthesis inhibitors in bacteria E.g. tetracyline, doxycycline Bind to 30S ribosomal subunit Inhibit translation by interfering with binding of tRNA to rRNA

what are tetracyclines?

parathyroid hormone Vitamin D and metabolites

what are the 2 key controlling factors of calcium?

diphtheria

what does Corynebacterium diphtheriae cause?

• Normal metabolism: oxidation of dietary carbohydrate, lipid and protein • In health, glycogen stores can maintain glucose for up to 24h • Brain has no glycogen store • Obligate substrate = glucose • Brain requires continuous supply of glucose and oxygen o Requirements: 120g/ day = 1kg muscle o Will not survive more than 2mins of circulatory failure o Adapts to using ketones as an energy substrate • Kidneys, liver: capable of gluconeogenesis o Can survive hrs of interruption of blood supply • Different tissues use different substrates o Liver and kidney: fatty acids or amino acids o Skeletal muscle: glycogen stores or fatty acids o Brain uses ketones

what happens to energy delivery in trauma?

osteoporosis

what is DEXA scanning used for?

hypothalamus

what is FSH releasing factor released by?

Procollagen type 1N propeptide o Synthesised by osteoblasts-->precursor molecule of type 1 collagen o Has low diurnal and intraindividual variation o Serum concentrations are not affected by food intake o Increased with increased osteoblast activity o Decreased by reduced osteoblast activity

what is P1NP?

Accumulation of pus within the brain tissue

what is a brain abscess?

bacterium with a shape intermediate between cocci and bacillus

what is a coccobacillus?

• Done before most transplants, this is where you take the donor's lymphocytes from the spleen or blood and add the serum of the recipient to see if you get cell lysis • Final check for compatibility • Final check to detect unexpected antibodies

what is a crossmatch?

a drug that kills cells e.g. in chemotherapy

what is a cytotoxic drug?

Calcium values can be corrected for changes in albumin • Adjusted Ca = Total Ca + [ (40 - Alb) x 0.025 ] • Reference range for adjusted calcium (LTHT) 2.2 - 2.6 mmol/L • Equation is not valid if albumin < 20 g/L • Recommend measuring ionised calcium on a point-of-care blood gas analyser.

what is adjusted calcium?

anything that can be bound by an antibody

what is an antigen?

Transient bacteria which are easily picked up and transferred, they are easy to remove Resident bacteria are deep seated and difficult to remove

what is an important cause of healthcare associated infections?

phosphatase involved in mineralisation and is released by osteoblasts

what is bone alkaline phospahatase?

osteoid

what is bone called before mineralisation?

o Muscle contraction o Neuronal excitation o Enzyme activity (Na/K ATPase, hexokinase etc.) o Blood clotting

what is calcium phsyiologically important for?

hepatocellular carcinoma

what is cirrhosis a common risk factor for?

beta lactamase inhibitor

what is clavulanic acid?

combination of processes that removes or destroys contamination so that infectious agents or other contaminants cannot reach a susceptible site in sufficient quantities to initaite infection or another harmful response

what is decontamination?

an antibiotic that interferes with RNA synthesis.

what is rifamycin?

to inform decisions on which antimicrobial agents to use in infection

what is sensitivity testing used for?

o ~ 30% of all hospitalised inpatients at any given time receive antibiotics o Over 30% of antibiotics are prescribed inappropriately in the community o Up to 30% of all surgical prophylaxis is inappropriate o ~ 30% of hospital pharmacy costs are due to antimicrobial use o 10-30% of pharmacy costs can be saved by antimicrobial stewardship programs o involves timely and optimal selection, dose and duration of an antimicrobial o for the best clinical outcome for the treatment or prevention of infection o with minimal toxicity to the patient o and minimal impact on resistance and other ecological adverse events such as C. difficile

what is the 30% rule with antimicrobial prescribing?

Minimum inhibitory concentration-->minimum amount of antibiotic that inhibits bacteria from growing There is intra-species variation i.e. bacteria within the same species will have different MIC values

what is the MIC?

paired through catheter and peripheral blood cultures Coagulase negative staphylococci is the most likely cause

what is the best test to confirm catheter associated blood stream infection? What is the most likely cause?

part of bone repair, where mature bone is removed and new bone tissue is formed

what is the bone cycle?

confusion

what is the curb 65 score used to assess?

Mainly collagen This extracellular portion also contains inorganic components like hydroxyapatite and minerals like calcium and phosphate

what is the extracellular matrix of bone made of?

its complications not its treatment

what is the majority of money on diabetes spent on?

80%

what is the oral bioavailability of ciprofloxacin?

• Apparent fluorescence of the nucleus only. • Target antigens - MPO (70%) and PR3. • ANCA is the pattern. • PR3/MPO is the auto-antibody causing the pattern.

what is the peri-nuclear ANCA pattern?

This is associated with increased clinical cure All antibiotics have this which is the maximum clinical benefit the drug can have, after this there is no additional efficacy benefit So, antibiotics are dosed to achieve this but not to exceed it (wasteful)

what is the pharmacodynamic target?

gives tensile strength

what is the purpose of collagen in the bone?

Increased bone remodelling like in: Childhood/prepubertal growth spurt Fractures Hyperparathyroidism Paget's disease of the bone-->interferes with your body's normal recycling process in which new bone tissue gradually replaces old bone tissue. Over time, the disease can cause affected bone to become fragile and misshapen.

what is the release of bone alkaline phosphatase stimulated by?

CTX: marker of bone resorption, if they are taking the drug, bone resorption should be reduced and there should be suppressed osteoclastic activity if they are taking the drug

what test could you perform to asess whether the patient was taking their bisphosphonate drugs?

amoxicillin

what would you treat low severity pneumonia with?

Unexplained loss of height Kyphosis--abnormal curvature in thoracic and spinal regions Severe back pain

when are you prompted to investigate vertebral fractures?

Decline

when infection resolves, what happens to levels of IgG?

before age of 45 years

when is menopause considered early?

at 12 weeks, and if this is normal then repeat at 24 then 28 weeks

when should gestational diabetes be tested for?

Use antivirals in HIV, hep B and hep C

when to use antivirals in chronic infection

Can occur anywhere in the large bowel from beginning (caecum) to the end (rectum) Most bowel cancers are more common in the left side of the bowel (descending colon), in the rectum and sigmoid colon

where are bowel cancers most common?

sigmoid colon

where are diverticula most often seen in the large bowel?

specfici isoenzymes

where there is diagnostic doubt of bone disease, what is measured?

IgG

which antibody is long lived?

IgM

which antibody marks acute infection?

fungi

which are least likely to acquire resistance out of bacteria, viruses and fungi?

O

which blood group can donate to anyone?

AB

which blood group can receive blood from anyone?

both

which causes antibiotics associated diarrhoea--oral or IV antibiotics?

IV because it also required medical staff to administer

which is cheaper oral or IV antibiotics?

raised

white blood cell count in bacterial infection?

normal

white blood cell count in viral infection

women in their menopausal years, loss of oestrogen in menopause causes loss of bone mass With increasing age, less bone is formed and more bone is resorbed

who loses bone faster: women or men?

Pertussis

whooping cough; highly contagious bacterial infection of the pharynx, larynx, and trachea caused by Bordetella pertussis Usually affect children before vaccine available, recent resurgence noted Clinical illness in 3 stages Catarrhal phase Cold-like (coryza, conjunctival irritation, occasionally a slight cough) 7-10 days Paroxysmal phase Long duration (2-6 weeks); No fever a series of rapid, forced expirations, followed by gasping inhalation the typical whooping sound Post-tussive vomiting common Very young infants may present with apnea or cyanosis in the absence of cough Convalescent phase Highly communicable acute respiratory infection caused by B. pertussis Person-to-person transmission through aerosolised respiratory droplets Humans are the sole reservoir Diagnosis : Culture & PCR in early stages Serology if illness > 3weeks

Because the mother's IgG is transferred to them in the final trimester

why does a newborn who may be immunosupressed have normal levels of IgG?

it makes you gain weight

why is being put on insulin a last resort for type 2 diabetics?

• Cause: positive for glandular fever, ALT is commonly raised with Epstein-barr virus, transient thing and can go down with illness, can get jaundice, enlarged spleen but sometimes only seen in a few people

• 13yr female GP patient • clinical details: sore throat • positive for infectious monucleosis screen • Raised ALT 262u/L (<40) • Bilirubin 7umol/L (<21) • ALP 622U/L (230-600): more likely to be due to growth spurt which is due to bone as ALP slightly raised, have age specific • Albumin 43g/L (35-45) What is the cause of liver damage?

• Cause: paracetamol overdose, IV fluids due to loss of electrolytes and potassium, acute hepatitis due to overdose

• 16yr old female • transferred from another hospital • clinical details: abdo pain, vomiting, uncommunicative o ALT: 1550 u/l (<40) o PT: 29s (9-14) o Ammonia: 250umol/L (<50) o Paracetamol at 12hr post admission: 197mg/L o Treated with N-Ac and Vit K What is the cause of liver damage?

• Consequences of Joe's fracture and internal injuries o Blood loss + impaired breathing + infection barrier penetration o Dec circulating volume o Dec red blood cells, dec oxygen o Dec white cells, dec immune response o Dec cardiac output/ BP o Dec organ perfusion o Dec energy substrate delivery to cells and tissues • Major organ dysfunction: GI, heart, brain, renal etc • Infection barrier penetration: sepsis

• Joe suffered multiple fractures and severe internal injuries in a motorcycle accident • As he could not eat or drink he was given iv fluids (3L 5% dextrose / day) • He lost weight rapidly and died 15 days later • The death certificate cited "Pneumonia" as the cause of death • What happened to Joe's energy metabolism?

o Amocixillin-clavulanate (Augmentin) - Increases the spectrum of amoxicillin o Piperacillin-tazobactam (Tazocin) - Increases the spectrum of piperacillin - ESBL and carbapenemase BLBLIs - Work in progress

• β-lactam/β-lactamase inhibitor combinations (BLBLI):