yr_3_revision_notes_for_common_diseases

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					                       Yr 3: Revision for common diseases
    Disease     Gastro-oesophageal reflux disease (GORD) Pg 250
Epidemiology  Gastrointestinal symptoms such as heartburn, acidity, pain, discomfort etc are very
                   common with 80% of the population saying they have suffered at some time.
   Pathology  Weakened oesophageal sphincter, allowing stomach acid contents up into oesophagus
                Stomach over producing acid, causing overflow to become more likely?
 Aetiology/RF  Pregnancy
                 Obesity
                 Large Meals
                 Cigarette smoking
                 Drugs (antimuscarinic, Calcium channel blockers, nitrates)
                 Systemic sclerosis
                 Hiatus hernia
                 After treatment for achalasia (decreased oesophageal motility)
     Signs/     Heartburn Pain:
   symptoms      Burning, worse on bending, stooping or lying down.
                 Seldom radiates to the arms
                 Worse with hot drinks/alcohol
                 Relieved by antacids
                Correlation between GORD and oesophagitis is poor.
                Psychosocial factors often determine symptom severity
                Regurgitation of food and acid into the mouth occurs particularly when lying flat
                Aspiration pneumonia rare
                Cough and asthma may occur and respond slowly.
    Similar     Cardiac Ischaemic pain. Different by:
   symptoms      Gripping/crushing
other disease  Radiates to neck/ L arm
                 Worse with exercise
                 Accompanied by dyspnoea
Investigations  Diagnosis can usually be made without investigation.
                 Investigations if alarm signs present (weight loss, protracted vomiting, anorexia,
                   haematemesis, melena or especially dysphagia)
                 Assess oesophagitis and hiatus hernia by endoscopy (if there is oesophagitis/ Barrett’s
                   oesophagus- reflux is confirmed)
                 Document reflux by intraluminal monitoring over 24hrs. Useful if PPI’s proving
                   ineffective/ going to have surgery. Excessive PH is <4 for more than 4% of the time.
T     Surgical  Surgery should never be performed for hiatus hernia alone.
r                Typical reflux symptoms, with documented acid reflux that responds to PPI’s produces
e                  the best results. The oesophagogastric junction is returned to the abdomen, gastric
a                  fundus is mobilized and diaphragmatic crura is closed.
 t Pharmaco  Alginate-containing antacids (gaviscon)
m cological  Dopamine antagonist prokinetic- speed up gastric emptying (metoclopramide)
e                H2 receptor antagonists- often used if PPI’s fail (cimetidine, ranitidine).
n                PPI’s inhibit gastric hydrogen/potassium- ATPase. Usually patients respond well, and
 t                 maintenance dose may be needed for life (omeprazole, lansoprazole).
                 If Pts do not respond to PPI’s may be called non-erosive reflux disease (NERD)- often due
                   to hypersensitivity in oesophagus.
                 H. Pylori eradication has little effect on symptoms but is advised (Amoxicillin,
                   clarithromycin and PPI).
       Non-            Weight loss
     Pharmaco          Raising head of bed at night
      logical          Dietary measures (eg curries avoided?)
                       Reduce alcohol intake
                       Smoking cessation

   Disease       Peptic Ulcer pg 259
Epidemiology        • Duodenal ulcers affect 10-15% of the adult population and are 2-3 times more
                         common than gastric ulcers.
                    • Ulcer incidence is decreasing rapidly in younger men and rising in older individuals
                         (esp women).
                    • More prevalent in developing countries due to H. Pylori.
    Pathology       • Breakdown in the superficial epithelial cells penetrating down to the muscularis
                         mucosa- a fibrous base with inflammatory cells.
                    • With no mucous/protection acid is capable of breaking down stomach/ duodenal
                         wall.
Aetiology/RF        • H. Pylori (80-90%)
                    • Smoking
                    • NSAIDS
                    • Reflux of duodenal contents
                    • Delayed Gastric emptying/ increased gastic acid production
                    • Stress
                    • Blood group
                    • Cushings and Cerlings ulcers
                    • Zollinger-Ellison syndrome
      Signs/         Burning epigastric pain (evidence to show if they point to the area with a single
    symptoms             finger it may be indicative of peptic ulcer disease).
                     Pain of DU classically occurs at night (as well as daytime) and worse when pt is
                         hungry (though may not be reliable).
                     Pain relieved in both GU and DU by antacids
                     Nausea- vomiting infrequent but may relive pain
                     Anorexia/ weight loss (esp GU’s)
                     Persistent severe pain- penetration into other organs?
                     Back pain- Penetrating posterior ulcer?
                     Melena!!
                     Maybe no symptoms
                     Untreated symptoms relapse and remit (due to atrophic gastritic and decreased acid
                         production)
   Similar           GORD
  symptoms           MI
other disease        AAA dissection
Investigations       13C-Urea breath test, stool antigen test, Serological tests for H. Pylori.
                     Biopsy urease, culture, histology- invasive for H. Pylori
T     Surgical      • Only used if there is recurrent uncontrolled heamorrhage or perforation
r                Types of surgery include:
e                    Partial gastrectomy
a                    Highly selective Vagotomy- Vagus is denervated where it supplies the lower
t                        oesophagus and stomach. Nerve of Latarget is left intact and so pyloric sphincter is
m                        left functional.
e                    Vagotomy and pyloroplasty- Vagotomy reduces acid production by body and fundus,
n                        and gastrin production from the antrum. However this affects the pyloric sphincter-
t                        so a drainage procedure (pyloroplasty) must be performed.
                       Gastrectomy is rarely required (zollinger- Ellison syndrome).
   Pharmaco         •   H.Pylori eradication (triple therapy is 80-85% effective)
    logical         •   Reduce acid- PPI’s, H2 receptor antagonists
                    •   Stop NSAID use (if possible)
     Non-           •   Avoid food that worsens symptoms
   Pharmaco         •   Stop smoking
    logical

   Disease          Acute upper gastro-intestinal bleed Pg 267
Epidemiology         In the developing world, haemorrhagic viral infections can cause significant GI
                       bleeding.
                     Overall incidence is falling.
                     Mortality from GI haemorrhage has remained at 5-12%
  Pathology          Breakdown in gastric mucosa for GU/DU
                     Vomiting tears mucosa in Mallory Weiss
                     NSAIDS- affect mucous/ bicarbonate production- so mucosa is not protected
Aetiology/RF         NSAIDS (aspirin)
                     Alcohol
                     Reflux oesophagitis
                     Oeasophageal/gastric varices
                     GU/DU
                     Gastric carcinoma (uncommon)
                     Haemorrhagic gastropathy and erosions
                     Mallory-Weiss syndrome
                     Other rare ones (pg 267 K+C)
   Signs/            Haematemesis
 symptoms            Melaena (dark red blood proximal to R colon)- bright red blood from upper GI bleed
                       has due be due to massive haemorrhage and pt will be in shock.
    Similar
   symptoms
other disease
Investigations
T     Surgical         Endoscopy
r                      Varices banded- perhaps stenting
e Pharmaco             Epinephrine and thermal coagulation (heater probe, bipolar probe, laser or argon
a      logical          plasma coagulation).
 t                     Omeprazole IV 80mg and the infusion
m                      Triple therapy to eradicate H. Pylori in chronic peptic ulcers
e       Non-           Aprrox 85% pts stop bleeding spontaneously within 48 hrs
n Pharmaco             Rockall scoring system (to assess rebleed/death risk).
 t     logical         Blatchford score
                       Stop NSAID use
                       Acutely procedures in place- oxygen, fluids, etc etc


   Disease       Acute lower GI bleed Pg 269
Epidemiology         Massive bleeding from lower GI tract is rare and often due to diverticular disease or
                         ischaemic colitis.
   Cause/            Small bleeds are often due to haemorrhoids or anal fissures
  Pathology          Ulcer of rectum
                     Chrohns/ulcerative/infective colitis- often associated with diarrhea
                       Diverticula
                       Polyps
                       Carcinoma
                       Ischaemic colitis
                       Angiodysplasia (vascular malformation of the gut)
                       Carcinoma of caecum
                       Meckels diverticulum
Aetiology/RF
   Signs/              Melena
 symptoms              Frank blood in stools
                       Blood around stools
                       Blood on tissue paper/ in pan
                       Pain?
   Similar             Inflammatory bowel disease
 symptoms/
other disease
Investigations         Flexible sigmidoscopy/colonoscopy (for IBD, cancer, ischaemic colitis, diverticular
                        disease, angiodyplasia)
                       Angiography- vascular abnormality
T  Surgical            Varices may be banded
r                      Haemorrhoids may be cauterised
e Pharmaco             Oral iron given if pt is anaemic
a   logical
t    Non-              If acute bleeding occurs and patient is haemodynamically unstable then
m Pharmaco              resuscitation is performed under same principles as upper GI bleed.
e   logical
n
t

   Disease       Inflammatory bowel disease Pg 285 (Crohn’s disease and Ulcerative colitis)
Epidemiology          CD incidence = 4-10 per 100000 annually, prevalence 27-106 per 100000
                      UC incidence = 6-15 per 100000 annually, prevalence 8-150 per 100000
                      Global variance, highest rates in northern Europe, UK, North America.
  Pathology           Autoimmune
                      Genetic susceptibility
                      Psychosocial factors
Aetiology/RF          Judaism
                      Females for CD
                      Males for UC
                      Genetic susceptibility
                      Environment (enteric microflora and nutrition)
                      Immune response

   Signs/              Diarrhoea
 symptoms              Abdominal pain
                       Weight loss
                       Malaise
                       Lethargy
                       Anorexia
                       Vomiting and low grade fever
   Similar             Megaloblastic anaemia
 symptoms/
other disease          Malnourishment
                       Ileocolonic tuberculosis
                       TB
                       Lymphoma
                       Bile acid mal-absorption
                       C Diff?
Investigations         Examination for both CD and UC- wt loss, apthous ulceration of mouth, abdo often
                        normal but tenderness in FIF possible. Anus should be examined for tags, fissures or
                        perianal abcesses.
                     Sigmoidoscopy and biopsy
                     Stool cultures
                 Blood tests:
                     Anaemia- normally normocytic (poss with iron/ folate deficiency). Megaloblastic
                        anaemia due to B12 deficiency is unusual
                     Raised ESR and CSR, WCC
                     Hypoalbuminaemia in severe disease
                     Liver biochemistry may be abnormal
                     Blood cultures may be needed if septicaemia suspected
                     Serological tests
T  Surgical          80% of pts with CD need an operation at some time.
r                    Stricturoplasty
e                    Resections of diseased gut removed
a                    Ileostomy/colostomy
t Pharmaco           Loperamide/codeine phosphate/co-phenotrope for diarrhoea
m   logical          Haematinics- Fe/B12/folic acid replacement
e                    Erythropoitin
n                    Glucocorticosteroids (eg prednisolone)
t
                     Some steroid sparing drugs (aminosalycates, azathioprine, 6-mercaptopurine)
                     Infliximab (an anti TNF-α monoclonal antibody) there are others.
     Non-            Smoking cessation
   Pharmaco          Enteric nutrition- low fat and low linoleic content for 28 days- good way to induce
    logical             remission

   Disease       Irritable bowel syndrome Pg 311
Epidemiology           Up to 1/5 patients in the UK report symptoms consistent with IBS
                       Costs healthcare resources £45.6 million per year
                       ¼ of IBS sufferers take 7-13 days of work per year
                       M:F ratio 2:3 (higher anxiety and depression scores in females- so more likely to
                         report disease).
 Pathology
Aetiology/RF           Infectious diarrhoea precedes onset of IBS in 7-30% cases
                       Females
                       Pre-existing life events
                       High hypochondriacal anxiety and neurotic scores
   Signs/              IBS co-exists with chronic fatigue syndrome, fibromyalgia and temporomandibular
 symptoms               joint dysfunction.
                     Painful periods, pain following sexual intercourse, premenstrual tension
                     Urinary frequency, urgency, nocturia, incomplete emptying of bladder
                     Back pain, headaches, poor sleeping, fatigue, bad breath
                 Diagnosed as in the preceding 3 months there should be 3 days per month of recurrent
                 abdominal pain or discomfort associated with 2 or more of the following:
                       Improvement in defeacation
                       Onset associated with change in frequency of stool
                       Onset associated with a change in form (appearance of stool)
                       This leads to 4 different sub groups of IBS sufferers based on symptoms
   Similar             Diverticulitis?
 symptoms/             IBD?
other disease
Investigations         History/consultation
                       Other investigation only takes place if pt has above symptoms and rectal bleeding,
                        nocturnal pain, fever, weight loss or if there is a suspicion of organic diarrhoea
T  Surgical
r Pharmaco             Kappa opioid agonists for patients suffering from patients in whom visceral
e   logical             hyperalgesia (increased sensitivity to pain).
a    Non-              Probiotics (containing live or attenuated bacteria) have been shown to reduce
t Pharmaco              symptoms and even act in a immunomodulatory role)
m   logical            Prebiotics (fermented by host bacteria and thus altering microbiota of host by
e                       stimulating growth of healthy bacteria)
n                      Eradicate dietary triggers
t                      High fibre diet and fibre supplements for constipation (ispaghula husk)
                       Antidiarrhoeal drugs for bowel frequency (loperamide, codeine phosphate)
                       Smooth muscle relaxants for pain (mebeverine hydrochloride, dicycloverine
                        hydrochloride, peppermint oil)
                       Psychotherapy
                       Hypnotherapy, cognitive behavioural therapy, antidepressants

   Disease       Infective gastroenteritis pg 128
Epidemiology          Children in developing world can expect 3-6 bouts per year
                      At least 2.25 million people per year die as a result of diarrhoeal disease
    Pathology         Viral- noroviruses
                      Protozoal and helminthic gut infections (more common in developing countries)
                      Bacterial infection (three different ways it can cause infection):
                 Mucosal adherence- moderate watery diarrhoea (E.coli)
                 Mucosal invasion- Dysentry (Shigella)
                 Toxin production- Profuse watery diarrhoea/ dysentery (vibrio cholerae, salmonella)
Aetiology/RF          Homosexuals
                      Children in daycare
                      Those in developing countries
      Signs/          Diarrhoea with or without vomiting
    symptoms          Split into two types:
                     1) Watery diarrhoea (usually due to enterotoxins or adherence)
                     2) Dysentery (usually due to mucosal invasion and damage)
   Similar            Malaria
  symptoms            UTI/ chest infections in elderly can have similar symptoms
other disease         C. Diff
Investigations        U+ E’s
                      Stool microscopy and culture
                      C.diff?
                      Blood culture
T     Surgical        N/A
r    Pharmaco          Antibiotics have a subsidiary role in some cases (can use stool culture to aid
e      logical            antibiotic therapy)
a   Non-             Oral rehydration/salt rehydration therapy
t Pharmaco           Assess for renal failure, perforation, septicaemia
m  logical           Inform public health
e                    Trace to source
n                    Avoid anti- motility agents
t

   Disease     Acute and chronic Pancreatitis Pg 377+380
Epidemiology       In most severe cases mortality can reach between 40-50%
   Cause/      Acute:
 Pathology         Speculation as to how a diverse group of aetiological factors can reach the same end
                      point
                   Suggestion that the final common pathway is a marked elevation of intracellular
                      calcium which in turn leads to activation of intracellular proteases. These are then
                      responsible for cellular necrosis.
                   Gallstones occlude the pancreatic drainage at the level of the ampulla leading to
                      pancreatic ductular hypertension.
                   Alcohol interferes with the calcium homeostasis in pancreatic acinar cells
               Chronic:
                   Inappropriate activation of enzymes within the pancreas
                   Chronic alcohol intake increases the levels of trypsinogen relative to its inhibitor
                   Precipitation of proteins in the duct lumen calcifies, leading to obstruction, ductal
                      hypetension and further pancreatic damage.
Aetiology/RF   Acute:
                   Gallstones (common)
                   Alcohol (common)
                   Infections (mumps, coxsackie B)
                   Pancreatic tumours
                   Drugs (azathioprine, oestrogens, corticosteroids, didanosine)
                   Iatrogenic (post surgical/ERCP)
                   Hyperlipidaemia’s
               Chronic:
                   Alcohol (by far the most common cause, accounting for 60-80% of cases)
                   Tropical (children and young adults genetic susceptibility + env factors)
                   Hereditary (Autosomal dominant condition)
                   Autoimmune (Middle aged men, associated with levels of IgG4)
                   Trypsinogen and inhibitory protein defects
                   Cystic fibrosis (almost all pts establish chronic pancreatitis)
                   Idiopathic
                   Trauma
                   Hypercalcaemia
   Signs/      Acute:
 symptoms          Is a differential diagnosis in anyone with upper abdominal pain
                   Pain usually starts in epigastrium and is accompanied by nausea and vomiting
                   Pain becomes more intense (due to more inflammation in peritoneal cavity)
                   Involvement in retroperitoneum frequently leads to back pain.
                   Pt may have had a previous similar episode or be known to have gallstones
                   Multi organ failure- major cause of initial morbidity
               Examination:
                   Pt in pain, upper abdominal tenderness with guarding as well as reduced or absent
                      bowel sounds
                   Severe necrotising pancreatitis can be associated with periumbilical (cullens sign)
                        and flank bruising (Grey- Turners sign)
                     Jaundice, cholangitis (with gallstones)
                     Pt may be tachycardic, hypotension and be oliguric
                 Chronic:
                     Epigastric pain radiating through to the back
                     Pattern of pain may be episodic, with short periods of severe pain with chronic
                        unremitting
                     Exacerbations of pain may follow further alcohol consumption
                     During periods of pain, anorexia is common and weight loss may be severe
                     Exocrine and endocrine insufficiency may develop at any time, and occasionally
                        malabsorbtion or diabetes is the presenting feature in the absence of abdominal
                        pain.
                     Jaundice
   Similar           Cholecystitis
 symptoms            Cholangitis
other disease        Hepatitis
                     Pancreatic malignancy
                     Pancreatic pseudocyst
Investigations       Blood tests- serum amylase, urinary amylase, serum lipase, CRP, FBC, U+E
                     Chest X-ray to exclude gastroduodenal perforation
                     Abdominal USS can be used to determine a possible biliary (gallstone) cause of
                        pancreatitis (may be difficult to detect)
                     Contrast-enhanced spiral CT scanning is essential in all but the most mild attacks of
                        pancreatitis. It should be performed after 72 hours to assess the extent of pancreatic
                        necrosis
                     MRI can assess the extent of pancreatic damage, especially to differentiate between
                        fluid and solid inflammatory masses.
T    Surgical        Nasogastric suction prevents abdominal distention and vomitus- decreasing the risk
r                       of aspiration pneumonia.
e                    Endoscopic intervention with sphincterotomy and stone extraction is only of proven
a                       benefit when the episode of pancreatitis is predicted as severe.
t                    MRCP
m                    Removal of gallstones at time of ERCP
e                    Cholecystectomy
n                Chronic
t                    Surgical duct drainage and partial resection of the diseased head of pancreas.

    Pharmaco           Prophylactic antibiotics
    cological          Parenteral nutrition
                       Anticoagulation- for DVT prophylaxis
                       Painkillers (NSAIDS and an opioid for chronic, or tricyclic antidepressants)
                       H2 receptor antagonists/PPI to help stomach acid and pancreatic juice mixing
                       Cystic fibrosis treatment if pt has it!
      Non-             Baseline ABG’s determine need for oxygen
    Pharmaco
     logical


    Disease      Gallstones Pg 367 (Pain= biliary colic, pain + temp= cholycystitis, Pain temp and jaundice=
                 cholangitis)
Epidemiology          May present at any age, but are unusual before the third decade
                      Increase in incidence with age
                       Prevalence is 2-3 times higher in women compared to men
                       More common in scandanavia, south America, and native north Americans (less
                        common in Asian and Africans)
  Pathology          2 types of gallstones, in 80% of cases in western world they contain cholesterol, the
                        other type are ‘pigment stones’- predominantly composed of calcium bilirubinate or
                        complexes of calcium, copper and some cholesterol.
                     Cholesterol gallstones are a result of cholesterol crystalisation from gall bladder bile,
                        dependent on cholesterol supersaturisation of bile, crystalisation-promoting factors
                        within bile, motility of the gallbladder.
Aetiology/RF         Increasing risk with age
                     Females more at risk
                     Family history
                     Multiparity
                     Obesity and metabolic syndrome
                     Rapid weight loss
                     Diet
                     Drugs
                     Ileal disease/resection
                     Diabetes mellitis
                     Liver cirrhosis
                     Acromegaly treated with octreotide
   Signs/            Majority of gallstones are asymptomatic and remain so during a persons lifetime
 symptoms            Once they become symptomatic however (20% of stones) there is a strong trend
                        towards recurrent complications, often of increasing severity.
                     Biliary colic type pain, constant pain with a crescendo characteristic
                     Pain often starts after fatty meal, most common time is mid evening lasting through
                        until early morning
                     Pain usually starts in epigastrium but may move to the RUQ, radiation may occur
                        over the right shoulder and right subscapular region.
                     Nausea and vomiting frequently accompany the more severe attacks and cessation
                        may be spontaneous
                     Fever and rigors suggests secondary complications such as cholecystitis, cholangitis
                        or gallstone related pancreatitis.
                     In acute cholecystitis above biliary colic pain can progress to localized RUQ pain
                        corresponding to parietal peritoneal involvement in the inflammatory process.
                        Associated with tenderness and guarding.
                     Very rarely, gallbladder can become distended by pus, and perforate causing
                        peritonitis.
   Similar           Differentials of biliary colic pain include IBS (spasm of the hepatic flexure)
 symptoms/           Carcinoma of the R side of the colon
other disease        Atypical peptic ulcer disease/perforated peptic ulcer
                     Renal colic
                     Pancreatitis
                     Acute episodes of pancreatitis
                     Intrahepatic abcess
                 Very rarely- MI or Basal pneumonia
Investigations       Abdo USS
                     Biliary scintigraphy using technetium derivatives of iminodiacetate.
                 Blood tests:
                     Detect moderate leukocytosis
                     Measure CRP levels
                     Serum bilirubin, alkaline phosphatase and aminotransferase levels may be raised in
                         cholecystitis alone. More significant is increases in bilirubin and alkaline
                         phosphatase with the diagnosis of bile duct obstruction.
T  Surgical             Cholecystectomy- choice of treatment for virtually all patients with symptomatic
r                        gallstones (should not be done without presence of symptoms). Some discussion
e                        about cholecystectomy as prevention in young patients with small stones going on to
a                        progress the condition or gallbladder pancreatitis.
t                       Stone dissolution and shock wave lithotripsy
m Pharmaco              Opioid analgesia
e cological             IV antibiotics
n    Non-               Acutely ill patients nil by mouth initially, IV fluids
t Pharmaco
    logical

   Disease       Bile duct stones Pg 370 (often only present after bile duct has obstructed and
                 cholecytitis/cholangitis is present)
Epidemiology
 pathology              Stones in common bile duct, causing blockeage.
                        Primary gallstone from liver, secondary gall stone from gallbladder
Aetiology/RF
   Signs/               Abdominal biliary colic pain
 symptoms               Fever (rare but indicates biliary sepsis/ septicaemia)
                        Jaundice
                        May be episodes of pain, some of which are accompanied by jaundice
                        May be asymptomatic
                        Tenderness in RUQ varying from mild to severe
                        More widespread abdo tenderness, extending from the epigastrium into the LUQ
                         may indicate pancreatitis.
   Similar              Cholangitis
  symptoms              Cholecystitis
other disease        
Investigations          FBC (usually normal)
                        Elevated neutrophil count and raised CRP
                        Mild raised serum bilirubin
                        Serum alk phos and gamma- glatamyl transpeptidase
                        Other bloods
                        Trans abdominal USS
                        Magnetic resonance cholangiography
                        Spiral CT scanning
                        Endoscopic USS
                        Endoscopic retrograde cholangiography (ERC)
T    Surgical           Bile duct drainage by an endoscopic retrograde approach
r                       Removal of CBD stones by endoscopic approach
e                       Laparoscopic cholecystectomy (if gallbladder stones are present also)
a Pharmaco              IV antibiotics
t   cological           Opioid analgesics
m
e      Non-           Fluids
n Pharmaco
t     logical
There are other conditions of biliary tract… Pg 372
   Disease     Viral Acute Hepatitis Pg 332
Epidemiology   Hepatitis A
                    Most common type of viral hepatitis worldwide, often in epidemics.
                    Seen in Autumn in children and young adults.
               Hepatitis B
                    360 million carriers worldwide (UK low with 0.5-2%).
               Hepatitis C (mostly chronic)
                    240 million people worldwide are infected.
                    Prevelance is 0.02% in northern Europe, 1-3% in southern Europe and 6% in Africa.
               Hepatitis D- chronic (brought on by Hep B)
               Hepatitis E:
                    Mortality of fulminant (sudden/severe) hepatic failure of 1-2%, which rises to 20%
                       in pregnant women.
 Pathology/         Hepatocytes show degenerative changes (swelling, cytoplasmic granularity,
   causes              vacuolation) and undergo necrosis (becoming shrunken, eosinophilic councilman
                       bodies)
                    The extent of damage is variable between individuals affected by the same agent
                    Portal tracts and lobules are also infiltrated with lymphocytes
                    Hep A- replicated in liver, excreted in bile, and then faeces 2 weeks before symptoms
                       arise and up to 7 days after. Spread by faeco-oral route/ingestion of contaminated
                       food/water. Can progress to chronic.
                    Hep B- Vertical transmission from mother to child in utero, IV spread through blood
                       contact, through abrasions as virus can last on objects for prolonged periods, semen
                       and saliva spread possible also. Can progress to chronic
                    Hep C- Spread by blood, limited sexual transmission. Other causes of spread are rare.
                       20% of cases origin is unknown. Can progress to chronic.
                    Hep E- does not progress to chronic. Enterally transmitted, usually by contaminated
                       water. 30% of dogs, pigs and rodents carry the virus.
Aetiology/RF   Causes of hepatitis (acute and chronic):
                    Viral-Hep A, Hep B, Hep D, Hep C, Hep E,
                    Autoimmune
                    Epsein- Barr virus
                    Cytomegalovirus
                    Drugs- Methyldopa, isoniazid, Ketoconazole, nitrofurantoin, paracetamol
                    Hereditary- Wilsons disease
                    Others- IBD/UC, Alcohol, toxoplasma gondii, Q fever, Pregnancy (can damage
                       panechymal cells- not necessarily hepatitis), aflotoxin, carbon tetrachloride

   Signs/      Hepatitis A
 symptoms          Nausea, anorexia
                   Distaste for cigarettes
                   After 1/2 weeks pt may become jaundiced- gradually getting worse producing dark
                      urine and pale stools.
                   Persistence of nausea, vomiting/ confusion warrants hospitalization
                   Liver moderately enlarged and spleen palpable in 10% of patients. Occasionally
                      lymphadenopathy is seen with a transient rash.
                   Jaundice lessens and illness is over in 3-6 weeks.
                   Extrahepatic complications include arthritis, vasculitis, myocarditis and renal failure.
               Hepatitis B
                   If host immune response is working, then disease clinical picture may be the same as
                      Hep A, although the illness may be more severe.
                   In addition a serum sickness-like immunological syndrome may be seen consisting
                        of rashes and polyarthritis affecting small joints
                     Arteritis/ glomerulonephritis
                 Hepatitis C
                     Most acute infections asymptomatic, 10% of pts have flu like symptoms with
                        jaundice and raised serum aminotransferases.
                     Later on- after chronic hepatitis for years undetected may have arthritis,
                        glomerulonephritis associated with cryoglubulinaemia, higher incidence of diabetes
                        etc
                 Hepatitis D:
                     Needs mentioning as it is only activated by Hep B virus, and complicates it.
                     Goes on to form chronic hepatitis.
                 Hepatitis E:
                     Clinically very similar to Hepatitis A
   Similar       Any other forms of hepatitis!
 symptoms/       Cholecystitis/cholangitis/ pancreatitis
other disease
Investigations   Hep A/ Hep B:
                     Liver biochemistry- Serum bilirubin normal, bilirubineria, an increased urinary
                        urobilinogen. Raised AST/ALT.
                     Haematological- Leucopenia with a relative lymphocytosis, in severe cases
                        prothrombin time is delayed. ESR is raised.
                     IgG markers for Hep A, HBsAg/ HBV markers for Hep B
                 Hep C:
                     Usually years later after chronic- Negative markers for other viruses, drug cause for
                        hepatitis should try to be excluded.
                 Hep E:
                     An ELISA for IgG and IgM and anti-HEV is diagnostic.

T  Surgical
r Pharmaco             Immunisation against Hep A, B.
e cological            Hep B: Antivirals (lamivudine) in very ill patients- unsure about efficacy. Also HBV
a                       markers monitored and nucleoside analogues given if they are still raised after 12
t                       weeks.
m                     Hep C: Interferon
e    Non-        Hep A: No treatment, most patients make a full recovery. Encourage hand hygiene. Mortality
n Pharmaco       in young adults is 0.1% (increases with age).
t   logical      Hep B: Most Pts recover. Fulminant Hep in 1% of cases, some develop chronic hep, cirrhosis,
                 hepatocellular carcinoma

Other infectious agents causing acute hepatitis include non A-E hepatitis, infectious mononucleosis,
cytomegalovirus, yellow fever, herpes simplex, toxoplasmosis (all on Pg 342).
Fulminant Hepatic failure (pg 342)

   Disease       Autoimmune hepatitis Pg 343
Epidemiology         Condition mostly occurs in women
 Pathology           Cause is unknown, it is proposed that in a genetically predisposed person, an
                       environmental agent causes a sequence of T cell mediated events against liver
                       antigens, producing a progressive necroinflammatory process which results in
                       fibrosis and cirrhosis. However no clear mechanism has been found.
Aetiology/RF         In type 1 there is an association with other autoimmune diseases (e.g. pernicious
                       anaemia, thyroiditis, coeliac disease and coombs- positive haemolytic anaemia).
                     60% have genetic links
   Signs/        Two peaks in presentation:
 symptoms            In the peri and post meonopausal group, pts may be asymptomatic or present with
                        fatigue, with the disease being discovered by abnormalities in liver biochemistry or
                        because of chronic liver disease on routine examination.
                     In the teens and early 20’s the disease (often type 2) presents as an acute hepatitis
                        with jaundice and very high aminotransferases that do not drop over time. Often
                        have clinical features of cirrhosis with hepatosplenomegaly, cutaneous striae, acne,
                        hirsuties, bruises and sometime ascites. Can also have features of autoimmune
                        disease with a fever, migratory polyarthritis, glomerulonephritis, pleurisy,
                        pulmonary infiltration or lung fibrosis. Overlap syndromes with primary biliary
                        cirrhosis and primary sclerosing cholangitis, existing together or developing
                        consecutively.
   Similar       Hepatitis viral?
 symptoms/
other disease
Investigations         Serum aminotransferases are high, with lesser elevations in the ALP and bilirubin.
                        The serum γ-globulins are high, particularly IgG
                       Haematologically normocytic anaemia with thrombocytopenia and leucopenia is
                        present, even before portal hypertension and splenomegaly.
                       Two different types of autoimmune hepatitis have been recognised.
                       Liver biopsy would show chronic hepatitis.
T  Surgical            Liver transplant if pharmacological intervention fails.
r Pharmaco             Prednisolone 30mg daily for 2 weeks, then slow reduction and maintainance of 10-
e cological             15 mg daily.
a                      Azathioprine 1-2g daily should be added as a steroid sparing agent, and may work in
t                       some patients as the sole maintenance therapy.
m                      With the above, remission occurs in 80% of cases.
e    Non-
n Pharmaco
t   logical


   Disease       Appendicitis Pg 315
Epidemiology         Most common surgical emergency.
                     Affects all age groups, and should always be kept as a differential in acute abdominal
                       pain if the appendix has not been removed.
  Pathology          Often a faecolith obstructs the lumen of the appendix, trapping faeces, which
                       becomes inflamed, swollen and infected.
                     In some cases there is just generalized acute inflammation.
Aetiology/RF
   Signs/              Abdominal pain, that starts vaguely in the centre of the abdomen, becoming localized
 symptoms               to the RIF within a couple of hours.
                       Examination shows there is guarding due to localized peritonitis, and may be a
                        tender mass in the RIF.
   Similar             Non-specific mesenteric lymphadenitis- may mimic appendicitis
 symptoms/             Acute terminal ilieitis due to crohns disease or Yersinia infection
other disease          Gynaelogical causes- ruptured ectopic pregnancy/ ovarian cysts, acute salpingitis.
                       Inflamed Meckels diverticulum
                       Functional bowel disease
Investigations         Raised WBC, ESR and CRP
                       Abdo USS can detect an inflamed appendix
                       CT in more detail and decreases risk of removing normal appendix.
T  Surgical            Appendicectomy (open or by laparascopic approach)
r Pharmaco             IV antibiotics (this is also the sole treatment for presence of appendix mass)
e cological            IV fluids
a    Non-
t Pharmaco
m   logical
e
n
t


   Disease       Small and large bowel obstruction Pg 317
Epidemiology         5th most common cause of acute Abdo pain
 Pathology           Obstruction is usually due to a mechanical block
                     Sometimes, bowel doesn’t function, leading to a paralytic ileus (occurs temporarily
                         after most operations and with peritonitis).
                     Leads to bowel dilation, increased secretion of fluid
                     Bacterial contamination may occur in stagnant bowel.
                     In strangulation, blood supply is impeded leading to gangrene, perforation and
                         peritonitis.
Aetiology/RF     Causes:
                 Small intestine
                     Adhesion (80% in adults)
                     Hernias
                     Crohn’s disease
                     Intussusception
                     Obstruction due to extrinsic involvement by cancer
                 Large intestine
                     Carcinoma of the colon
                     Sigmoid volvulus
                     Diverticular disease
                 Both: Strangulation
      Signs/         Pt complains of abdominal colic pain
    symptoms         Vomiting and constipation without passage of wind (in upper gut obstruction
                         vomiting is profuse, but may be absent in lower gut)
                 Examination:
                     Tender distended abdomen with increased bowel sounds
                     Marked tenderness suggests strangulation and urgent surgery is needed
                     Examination of hernia orifices and rectum necessary
                    
   Similar
 symptoms/
other disease
Investigations         X ray shows distended loops of bowel proximal to the obstruction. Fluid levels are
                        seen in small bowel obstruction on an erect film. In large bowel obstruction, the
                        caecum and ascending colon are distended
                       Water soluble gastrografin enema without air insufflation may help to demonstrate
                        the obstruction
                       CT can localise lesion accurately and is the investigation of choice.
                       FBC, U and E’s
T     Surgical         Exploratory laparotomy, removing obstruction.
r                      Gut resection if strangulation and gangrene have occurred
e                      In cases of large bowel malignancy, stents are being used followed by elective
a                       surgery
t                      Critically ill patients may require a defunctioning colostomy
m                      Management of sigmoid volvulus can be achieved through insertion of a flexible
e                       sigmoidoscope/rectal tube to un-kink the bowel- if recurrent it may require sigmoid
n                       resection.
t Pharmaco             Analgesics
   logical
    Non-               Resuscitation with IV fluids
  Pharmaco
   logical


   Disease       Femoral Hernia pg 630 OHCP and GP Notebook
Epidemiology          More prevalent in females
 Pathology            Bowel enters the femoral canal, presenting as a mass in the upper medial thigh or
                         above the inguinal ligament, where it points down the leg (unlike an inguinal hernia
                         which points to the groin.
                      Are likely to be irreducible and strangulate
                      Boundaries of femoral canal are anteriorly and medially- the inguinal ligament,
                         laterally the femoral vein, posteriorly the pectineal ligament and pectineus.
                      Canal contains Cloquets node
Aetiology/RF     Increased intra-abdominal pressure:
                      pregnancy
                      chronic cough
                      gastrointestinal obstruction
                      excessive straining e.g. occupations involving lifting heavy weights
                 laxity or weakness of tissue:
                      pregnancy
                      rapid weight loss
                      previous inguinal or femoral hernia repair
      Signs/          Neck of hernia is felt inferior and lateral to the pubic tubercle (small and grapelike)
    symptoms          Many femoral herniae are asymptomatic until incarceration or strangulation occurs
                      May be just an occasional dragging or aching sensation at the site
   Similar            Inguinal hernia
 symptoms/            Enlarged lymph nodes
other disease         Ectopic testes
                      Cyst of canal of Nuck
                      Saphena varix
                      Varicocoele
                      Psoas abscess
                      psoas bursa
                      Lipoma
                      Hydrocoele of spermatic cord
Investigations        Blood tests
                      USS
T     Surgical        Has to be done, without delay- due to likelihood of strangulation
r                3 different surgical approaches:
e                     Inguinal or 'high' approach
a                     Crural or 'low' approach
t                     Transperitoneal approach
m                • All of the above have the aim of reduction or excision of the hernial sac and reinforcement
e                       of the femoral canal
n   Pharmaco
t   cological
      Non-             Truss is not possible, due to difficulty fitting and likelihood of strangulation.
    Pharmaco
     logical


   Disease       Inguinal Hernia Pg 632 OHCM
Epidemiology         Most common type of hernia
 Pathology           Indirect hernias involve the protrusion of peritoneum through the deep inguinal ring
                        (mid point between ASIS and PT), and if large through the superficial ring (superior
                        and medial to the PT). Lateral to the inferior epigastric artery.
                     Direct inguinal hernias force their way directly through the posterior wall of the
                        inguinal canal into the abdominal wall. Medial to the inferior epigastic artery.
Aetiology/RF         Chronic cough
                     Constipation
                     Urinary obstruction
                     Heavy lifting
                     Ascites
                     Previous abdominal surgery
                     Obesity
    Signs/           Visible lump in scrotum, may be present all the time or be worse standing or after
  symptoms              coughing. Sometimes reduceable.
   Similar           Femoral hernia
 symptoms/           Undescended testes
other disease
Investigations         Abdominal USS
                       Bloods
                       Examination
T  Surgical            Surgical meshing (lichtenstein repair) reinforcing the anterior abdominal wall
r Pharmaco             Painkillers
e cological            Fluids
a    Non-              Advice on weight loss (rapid weight loss can however increase risk!!)
t Pharmaco             Advice to stop smoking
m   logical            Truss
e
n
t


   Disease       Breast Abcess
Epidemiology
 Pathology       Mastitis is an inflammatory condition of the breast. This may or may not be accompanied by
                 infection of the breast
                 In around 3% of patients, mastitis may be complicated by a breast abscess.

                 Common organisms responsible for mastitis and breast abscess are

                 • Staphylococcus aureus – most common
                 • Esherichia coli (or other gram negative bacteria)
                 • Bacteroides
                 • streptococci (alpha, beta and non-haemolytic)

                 The majority of breast infections may be divided into four groups:

                 •   Neonatal infection
                 •   Infections in lactating women
                 •   Infections in non-lactating women
                 •   Infections resulting from localised skin infection
Aetiology/RF
   Signs/        • Red, swollen, inflamed area of the breast
 symptoms        • Breast is hot to touch
                 • Fever of >38°C
                 • Flu-like symptoms which include chills, headache, muscle aches
                 • Painful lump caused by a blocked duct
   Similar       Fibrocytic disease
 symptoms/
other disease
Investigations        •   Mammogram
                      •   Fine needle biopsy
T  Surgical
r Pharmaco
e cological
a    Non-
t Pharmaco
m   logical
e
n
t


   Disease       Breast: Fibrocytic disease
Epidemiology     Fibroadenosis or fibrocystic disease is the most common cause of breast lumps in women of
                 reproductive age. The peak incidence is between 35 and 50 years of age. It is rare before 25
                 years
  Pathology      A spectrum of histologic changes, and may encompass many patients who have cystic
                 lesions detected clinically or sclerotic breast lesions detected on mammography as
                 discussed elsewhere.

                 Histologically it is characterized by overgrowth of both fibrous stroma, and of epithelial
                 elements i.e. ducts and lobules, in differing proportions. These changes may be considered
                 as abberations of normal breast involution and not part of a disease process. The condition
                 may be due to a disordered or imbalanced response to endogenous sex hormones.

                 Only in those cases showing marked epithelial hyperplasia - epitheliosis - is the risk of
                 breast carcinoma thought to be increased

                 A variety of changes may be noted including:

                 • cysts:
                 microcysts - less than 1 cm in diameter
                 macrocysts - up to 5 cm in diameter; includes the blue domed cysts of Bloodgood which
                 unopened, appear brown to blue due to the contained fluid
                 • apocrine metaplasia - the normal ductular epithelium that lines the cyst proliferates to
                        resemble that of apocrine sweat glands
                  • fibrosis - proliferation of fibrous tissue without epithelial change
                  • adenosis:
                  simple adenosis - hyperplastic proliferation of lobular acini / ductules
                  sclerosing adenosis - proliferation of fibrous tissue accompanies that of the acini, splitting
                  them apart

Aetiology/RF
   Signs/         Typically, patients present with one or more lumps in the breast which may be painful, and
 symptoms         frequently, bilateral. The size and pain usually vary with the menstrual cycle. One or more of
                  these elements may be absent.

                  Cysts are more common in perimenopausal women. They are usually single. The presence of
                  multiple, diffuse cysts may be referred to as Schimmelbusch's disease. The discharge varies
                  from clear to green but should not be bloodstained.

                  On palpation, a cyst may be recognised by its smooth texture and characteristic tense
                  fluctuation

     Similar
   symptoms/
other disease
Investigations
T      Surgical   A discrete lump thought clinically to be a cyst should be aspirated. The lesion is benign if:
r
e                 • the fluid is not bloodstained
a                 • the lump completely disappears
 t                • the cyst does not refill
m                 • cytology is negative
e                 If the lump is solid, or one of the above conditions is not upheld, mammography or
n                 preferably, excision biopsy is indicated
 t
     Pharmaco     Pain that is localised, is normally relieved by excision. Pain that is diffuse, cannot be relieved
      cological   by excision. In these cases, bromocriptine, or danazol, may be helpful.

      Non-        Carcinoma must be excluded.
    Pharmaco
     logical



    Disease       Breast: Ductal papilloma
Epidemiology
   Pathology
 Aetiology/RF
     Signs/
   symptoms
    Similar
  symptoms/
other disease
Investigations
T     Surgical
r Pharmaco
e     cological
a   Non-
t Pharmaco
m  logical
e
n
t


   Disease     Breast carcinoma Pg 487
Epidemiology       Most common cancer in women who don’t smoke
                   Screening programme of mammography every 3 years for women between 50-70
                       has greatly improved overall survival rates and cure.
                   Breast cancer is the commonest malignancy in women, accounting for 20% of all
                       cancer deaths in females. 1 in 11 females will get breast Ca.
                   Breast reconstruction surgery has improved greatly reducing the psychosexual
                       impact of the disease.
 Pathology         Majority of breast cancers arise from the epithelium of the milk ducts (most common
                       is an infiltrating ductal carcinoma).
                   Some feel that there is an in situ stage, but others feel it is too brief/ non existent to
                       not be detectable
                   In approximately 10% of women there are detectable mutations in the
                       BRCA1/BRCA2/TP53, accounting for <5% breast cancer.
                   Hormonal environment pays a huge role in cancer development
Aetiology/RF       Hormonal imbalance
                   Diet
                   Exercise
                   Weight
                   Oral contraception
                   Postmenopausal weight therapy
   Signs/          Painless increasing mass, which may also be associated with nipple discharge, skin
 symptoms              tethering, ulceration.
                   In inflammatory cancers oedema and erythema may be present also (peau d’orange)
               Breast cancer may be asymptomatic, occurring as an impalpable lesion on screening
               mammogram. (Up to 70% of important mammographic lesions are impalpable)

               In other cases, patients may present with:

               •   palpable breast lump:
               ◦           40-50% in the upper outer quadrant
               ◦           70-80% scirrhous i.e. hard and encapsulated
               ◦           may be tethered to superficial or deep structures
               ◦           does not fluctuate or transilluminate
               ◦           15-40% multicentric
               ◦           bilateral in up to 30% of cases of lobular carcinoma
               ◦           frequently, patient detected
               •   skin changes:
               ◦           dimpling
               ◦           peau d'orange
               ◦           nipple "eczema" in Paget's
               ◦           visible lump
               ◦           surface ulceration; neglected carcinoma in elderly
               •   recent nipple inversion
               •   bloodstained nipple discharge - uncommon
                 • non-cyclic breast pain - usually, a late sign
                 • disseminated disease:
                 • bone pain, pathological fracture, dyspnoea, pleural effusion hepatomegaly, jaundice
   Similar           Breast cyst
 symptoms/           Breast fibrocytic disease
other disease
Investigations        Palpation
                      Radiology (mammography/ USS/MRI)
                      Fine needle aspiration cytology is most accurate way to differentiate it from benign
                       breast masses.
                     Followed by large bore core needle biopsy to provide histological confirmation, and
                       predictive factors such as the grade and oestrogen, progesterone and Her2 receptor
                       status to aid diagnostic process.
                 Prognostic factors-
                     Size of primary tumour
                     Histological subtype
                     Histological grade/differentiation
                     Oestrogen and progesterone receptor status
                     Menopausal status
                     Her2 status
                     No of mets/ where they are/ their size
T  Surgical          Can vary from wide local excision or segmental mastectomy and breast conservation
r                      for masses <4cm to breast mastectomy with/without reconstruction.
e                    Choice dependent on location and size of mass in relation to breast size and patient
a                      preferences.
t                    Surgery of axilla is by sentinel lymph node guided sampling (after dye injection) in
m                      the absence of clinical/radiological evidence of lymphadenopathy or full dissection if
e                      there are nodes involved. The greater the surgery- the greater the risk of
n                      lymphedema.
t Pharmaco           Oestrogen/ progesterone receptive cancers- tamoxifen. In postmenopausal women
  cological            with receptor positive disease aromatase inhibitors such as anastrozole are also of
                       use and the relative benefits of each drug are of controversy.
                     Her2 expressing malignancy can be targeted with IV trastuzumab/ lapatanib.
                     Bisphosphonate therapy- reduces osteolytic deposits, bone pain and fracture and in
                       treating pain and hypercalcaemia in established bone mets
     Non-            Radiotherapy is given after wide local excision to reduce local recurrence, and to the
   Pharmaco            chest wall after mastectomy if there are risk factors such as proximity to the surgical
    logical            margins/ lymph node mets.
                     Radiotherapy can be added to the axilla after sampling, but not after full dissection
                       as the risk of severe lymphoedema rises to 30%.
                     Chemotherapy (for women with high risk features)

   Disease       Myocardial infarction/ acute coronary syndrome Pg 752
Epidemiology         The 1 month mortality in patients with MI may be as high as 50% in the community,
                         with 50% of deaths occurring within 2 hours of the event.
                     With hospital treatment, the mortality may be as low as 6-7% after 1 month
  Pathology          Rupture or erosion of a vulnerable coronary artery plaque can produce a prolonged
                         occlusion of a coronary artery leading to myocardial necrosis within 15-30 minutes.
                     Subendocardial myocardium is initially affected, but prolonged ischaemia causes the
                         infarct zone to spread through the subepicardial myocardium, producing a
                         transmural Q-wave MI.
Aetiology/RF     TIMI risk score for STEMI can be calculated based on:
                       Age (over 65/75)
                       Hx angina
                       Hx Hypertension
                       Hx diabetes
                       Weight
   Signs/              Severe chest pain lasting more than 20 minutes it may be MI, may radiate to left arm,
 symptoms               neck or jaw
                       May not be in pain!
                       Pain doesn’t usually respond to GTN
                       Dyspnea, fatigue, syncope
                       Patient is pale and clammy, sweating
                       Pulse is thready with hypotension, bradycardia or tachycardia.
   Similar             GORD
 symptoms/             Angina
other disease          Peptic ulcer
                       Pancreatitis
                       Pericarditis
                       Aortic dissection
Investigations         ECG
                       Blood samples for cardiac troponin I or T levels or CK-MB according to hospital
                        protocol, although treatment should not be deferred until the results are available.
                       FBC, serum electrolytes, glucose and lipid profile should also be obtained.
                       Transthoracic echocardiography may be useful to confirm diagnosis.
T  Surgical            Coronary angioplasty/ angiography
r Pharmaco             Opioid analgesia (morphine/ diamorphine)
e cological            Aspirin and
a                      Anti platelet- clopidogrel (300mg orally)
t                      GTN
m                      Oxygen
e                      Beta blockers if ongoing pain/ hypertension/ tachycardia
n                      Fibrinolytic agents- streptokinase/ tissue plasminogen activator/ heparin
t
                       Long term- antihypertensives, beta blockers, statins
     Non-              Quit smoking
   Pharmaco            Loose weight/ diet advice
    logical            Moderate exercise

   Disease       Angina Pg 748
Epidemiology         More than 1.4 million people in the UK suffer from angina
                     Coronary artery disease accounts for 3% of hospital admissions in England.
                     Prevalence of angina is approximately 2% with an incidence of new cases each year
                        as 1 per 1000.
  Pathology          Diagnosis mostly made by Hx, involves the narrowing of coronary arteries,
                        decreasing blood supply and thus oxygen/ nutrient supply to myocardium causing
                        pain.
Aetiology/RF
   Signs/              Heavy/tight/gripping chest pain centrally/retrosternal and may radiate to the
 symptoms               arms/ jaw
                       Pain can vary from mild ache to severe pain that provokes sweating and fear.
                       May be associated with breathlessness
                       Check BP and for signs of anaemia, hyperlipidaemia or thyrotoxicosis, also check for
                        aortic stenosis (this may be the cause).
                 Classical/ exertional angina pectoris-
                      Provoked by physical exertion (esp after meals/cold weather) and made worse by
                         anger/excitement.
                      Pain fades quickly at rest, occasionally it disappears with continued exertion
                      Threshold of pain onset may be predictable, but in most cases its variable
                 Decubitus angina-
                      Occurs when lying down (often in association with impaired left ventricular function
                         as a result of severe coronary artery disease).
                 Nocturnal angina-
                      Occurs at night and may wake the patient from sleep, can be provoked by vivid
                         dreams.
                      Tends to occur in patients with critical coronary artery disease and may be the result
                         of vasospasm
                 Variant (prinzmetal’s) angina-
                      Angina that occurs without provocation, usually at rest as a result of coronary artery
                         spasm.
                      More frequent in women
                      Characteristically there is ST elevation on the ECG during the pain
                      Specialist investigations may be needed to confirm the diagnosis
                      Arrhythmias may occur during the ischaemic period.
                 Cardiac syndrome X-
                      Good history of angina, a positive exercise test and angiographically normal arteries
                      Form a heterogeneous group, much more common in women.
                      Often have a good prognosis, they are however often highly symptomatic and can be
                         difficult to treat
                      Myocardium shows an abnormal metabolic response to stress, suggesting ischaemia
                         results from abnormal dilator responses of the coronary microvasculature to stress
                 Unstable angina-
                      Angina of recent onset (< 1 month)
                      Worsening angina, or angina at rest (or rapidly decreasing exercise levels)
                      Often falls under acute coronary syndrome.
   Similar            MI
 symptoms/            GORD
other disease         Aortic dissection
                      PE
Investigations        Resting ECG (usually normal between attacks). During an attack- transient ST
                         depression, t wave inversion or other changes to the shape of the T wave may occur.
                      Exercise ECG- may be useful to determine diagnosis and indication of coronary
                         artery disease. ST segment depression of over 1mm suggests myocardial ischaemia,
                         particularly if chest pain is present at the same time. Strongly positive test (within 6
                         mins of the start suggests ‘prognostic’ disease and helps to identify patients who
                         should be offered coronary intervention. Test can however be misleading- a normal
                         test does not exclude CAD and 20% of those with positive exercise tests are
                         subsequently found to have no evidence of coronary artery disease.
                      Cardiac scintigraphy- myocardial perfusion scans at rest and after stress are helpful.
                         Redistribution of a contrast agent is a sensitive indicator of ischaemia and can be
                         useful to determine whether a stenosis seen at angiography is giving rise to
                         ischaemia.
                      Echocardiography- used to assess ventricular wall involvement and function at rest,
                         and a stress test may be useful.
                      CT coronary angiography- increasingly being used to rule out other causes of pain.
                      Cardiovascular magnetic resonance imaging.
                       Coronary angiography- often used to delineate the exact coronary anatomy in
                        patients who are being considered for revascularization. Should only be used in
                        patients when the benefit of diagnosis and potential treatment outweighs the small
                        risk <1 in 1000 cases mortality
T     Surgical         Coronary artery bypass grafting (CABG)- veins or arteries are grafted to the
r                       ascending aorta and native coronary arteries distal to the area of stenosis. Risks-
e                       <1% mortality and perioperative strokes in 2%.
a                      Percutaneous transluminal Coronary angioplasty (PTCA) is the process of dilating
t                       coronary artery stenosis using an inflatable balloon into the arterial circulation via
m                       the femoral, radial or brachial artery. Coronary artery anatomy determines the
e                       success of PTCA. Involvement of metal stents aided process and reduced need for
n                       revascularization. Risks- MI (2%) and death (1%).
t                      Trials show PTCA has fewer adverse events and better patient survival at 18 months
                        (96.9% survival compared to 92.5%). However there was significantly higher need
                        for revascularization in the PTCA group.
     Pharmaco          Medication to treat anaemia/hyperthyroidism
     cological         Statins
                       Beta blockers
                       Calcium channel blockers/potassium channel blockers
                       Sodium channel interacting drugs- Ranolazine
                       GTN
                       Aspirin
                       Long acting nitrates (e.g. isosorbide mononitrate)
                       Cardiac pacemaker drugs- ivabradine
       Non-            Smoking cessation
     Pharmaco          Weight loss
      logical          Regular exercise

   Disease       Atrial fibrillation Pg 724
Epidemiology          Common arrhythmia occurring in 5-10% of patients over 65 years old, can also
                          occur (esp in paroxysmal form) in younger patients.
    Pathology         Can be caused by raised atrial pressure, increased atrial muscle mass, atrial fibrosis,
                          or inflammation and infiltration of the atrium.
                      Rheumatic disease, alcohol intoxication and thyrotoxicosis are classic causes,
                          hypertension and heart failure are the most common.
                      Hypertension must be considered in all those with AF
                      Many other causes including, hpt, congestive HF, thyrotoxicosis, CAD, caffeine,
                          smoking etc etc (pg 723)
                      Some there is no cause to be found- they are called ‘lone’ AF- suggestions about
                          genetic cause. Especially as 30/40% of those with AF have at least one parent with
                          AF
                      Only a proportion of the electrical impulses in the atria reach the ventricles.
Aetiology/RF          Hypertension
                      Heart failure
      Signs/          Symptoms can be very variable, in 30% of patients it is an incidental finding
    symptoms          Most experience some deterioration in exercise capacity or well being, but this may
                          only be appreciated when sinus rhythm is restored.
                      When caused by rheumatic mitral stenosis, the onset of AF results in considerably
                          worsening cardiac failure.
                      Irregularly irregular pulse
  Similar             Atrial flutter?
symptoms/             Atrial ectopic beats
other disease          Ventricular arrhythmias?
Investigations         ECG shows fine oscillations of the baseline (fibrillation/f waves) and no clear P
                        waves. QRS is rapid and irregular. Untreated, ventricular rate is usually 120-180 per
                        minute.
T  Surgical         
r Pharmaco             Ventricular rate control- managed by drugs that block the AV node (digoxin, CCB,
e cological             Beta blockers) or…
a                      Ventricular rhythm control- Cardioversion by use of IV antiarrhythmic drugs
t                      If cardioversion is planned, pt is fully anti-coagulated (INR 2-3) for 3 weeks prior
m                       and at least 4 weeks after (then long term use is assessed)
e    Non-              Alcohol abstinence (if alcohol toxicity is cause)
n Pharmaco             Hyperthyroidism/chest infection should also be treated if they are the cause.
t   logical            Cardioversion by DC shock

   Disease       Essential hypertension Pg 798
Epidemiology         Essential (idiopathic) hypertension is the cause of 80-90% of patients with elevated
                        blood pressure.
                     Depending on the diagnostic criteria, it is present in 20-30% of the adult population,
                        but is much higher in black Africans (40-45% adults)
  Pathology          Cause of essential hypertension is unclear, however it is known that the risk of
                        mortality and morbidity rises progressively with rising systolic and diastolic
                        pressures.
                     In chronic hpt the cardiac output remains the same but systemic resistance is
                        increased (increased wall diameter and decreased lumens). Large vessels also show
                        structural changes- deposition of calcium and increase in collagen (loss of
                        compliance)
                     Atheroma can develop
                     Left ventricular hypertrophy occurs
                     Reduced renal perfusion and greater GFR (may then activate the RAAS system in
                        cycle)
                     Hypertensives have a six-fold increase in the risk of stroke and a threefold increase
                        in the risk of cardiac death.
Aetiology/RF     Essential hypertension has multifactorial aetiology:
                     Genetic factors- Hpt tend to run in families, may be explained by environment but
                        most think there is an unidentified genetic component.
                     Foetal factors- low birth weight is linked to high blood pressure. May be due to
                        Foetal adaption to intrauterine undernutrition with long term changes in blood
                        vessel structure and the function of crucial hormonal systems.
                     Envoronmental factors- obesity (have a higher blood pressure), Alcohol intake
                        (blood pressure can be linked to alcohol consumption. However surprisingly those
                        who drink small amounts have been shown to have a lower blood pressure than
                        those who consume no alcohol), sodium intake (has been proposed as a major
                        determinant), Stress (short term pain/ stress can increase blood pressure but effects
                        in long term are unknown).
                     Hormonal mechanisms- Autonomic, RAAS, natriuretic peptide and kallikrein-kinin
                        systems play a role in the short term regulation of blood pressure.
                     Insulin resistance- link between diabetes and hypertension has long been
                        recognized (can be called the metabolic syndrome) is a major risk factor for
                        cardiovascular disease.
   Signs/            Usually asymptomatic (attacks of sweating, headaches and palpitations point
 symptoms               towards phaechromocytoma)
                     Higher blood pressures may be associated with headaches, epistaxis or nocturia.
                       Breathlessness may be present due to LV hypertrophy or cardiac failure.
                       Features of angina/ Peripheral vascular disease may point to renal artery stenosis.
                       Raised blood pressure on a sphygmanometer
                       Renal bruits should be listened for and radio femoral delay in coarctation of aorta.
                       If cardiac failure develops then there may be sinus tachycardia and a third heart
                        sound.
                       Fundus examination is crucial in hypertensive patients
   Similar
 symptoms/
other disease
Investigations         Blood pressure monitored using sphygmanometer
                       Ambulatory blood pressure monitoring – over a 24 hour period to assess whether
                        ‘white coat hypertension’ is present. Shows that those who have lost nocturnal fall in
                        blood pressure (‘non dippers’) have a worse prognosis.
                       ECG
                       Urine stick test for protein and blood
                       Fasting blood for lipids (total and HDL cholesterol) and glucose
                       Serum urea, creatinine and electrolytes (to check renal function)
T  Surgical
r Pharmaco             Patients have to have recurrent raised blood pressures. Age and level of
e cological             hypertension affect which drugs to start them on. Aim for 140/85 is aimed for.
a                     ACE inhibitors
t                     Angiotensin 2 antagonists (less side effects than ACE- no cough etc)
m                     Calcium channel blockers (CCB)
e                     Beta Blockers
n                     Diuretics
t                     Alpha blockers
                      Renin inhibitors
                 http://www.nice.org.uk/CG034.
     Non-             Unless it’s malignant hypertension the patient should have a period of assessment
   Pharmaco             and advice prior to the start of drug therapy.
    logical           Weight reduction (should be <25kg/m2)
                      Low fat and saturated fat diet
                      Low sodium diet (<6g day)
                      Limited alcohol intake (<21 units for men and <14 women per week)
                      Dynamic exercise (>30 mins per day)
                      Increased fruit and veg consumption
                      Stop smoking
                      Increase oily fish consumption

   Disease       Deep vein thrombosis Pg 809
Epidemiology
 Pathology
Aetiology/RF     Remember Virchovs triad!
                     Periods of immobilization
                     Prostactectomy (DVT occurs in 50% patients post operatively without prophylactic
                      heparin).
                     Previous CVA
                     AF
                     Hypertension/ hyperlipidaemia
                     Overweight
                        Smoking
   Signs/               May be asymptomatic, or presenting with features of PE.
 symptoms               Pain in the calf, often associated with swelling, redness and engorged superficial
                         veins. Often warmer with ankle oedema
                        Homans sign- pain in calf upon dorsifexion of foot is often present but not diagnostic
                         as it occurs in all lesions of the calf.
                        In the ileofemoral region can be painful but shows few signs other than occasional
                         thigh swelling and ankle oedema.
                        Complete occlusion can lead to cyanotic discoloration and severe oedema, rarely
                         leading to venous gangrene.
                        PE can occur from any DVT but is more common from ileofemoral thrombosis and is
                         rare to DVT’s below the knee.
                        In 20-30% of patients the spread of thrombosis can spread proximally with few new
                         symptoms so careful monitoring- often with USS is needed.
                        Venous eczema, swollen limb and oedema in long term due to damage of venous
                         valves.
   Similar              Acute peripheral artery disease
 symptoms/              Anaphylactic reaction?
other disease
Investigations          Clinical diagnosis is unreliable and should be combined with D-dimer levels.
                        Ileofemoral thrombosis can usually be confirmed using B mode venous compression,
                         ultrasonography or Doppler ultrasound.
                        Below knee DVT’s can only be detected reliably with venography, USS, fibrinogen
                         scanning and impedence plethysmography
T  Surgical             In extreme cases, leg amputation (may even be a preventative )
r Pharmaco              Low molecular weight heparins
e cological             Once INR is reached (2.5), patient starts on warfarin (usually for 3 months)
a                       Recurrent DVT’s require continuous anticoagulants
t                       Thrombolytic therapy may be used in some patients with large ileofemoral
m                        thromboses as the heparin will not lyse the thrombus that is already present.
e    Non-               Pressure stockings after event and on long haul flights
n Pharmaco              Weight loss
t   logical             Smoking cessation

   Disease       Left ventricular failure
Epidemiology
 Pathology       Commonest causes of left ventricular failure are: myocardial ischaemia, hypertension, aortic
                 stenosis or aortic incompetence, mitral incompetence.
Aetiology/RF
   Signs/        Possible symptoms: exertional dyspnoea (precedes orthopnoea and paroxysmal nocturnal
 symptoms        dyspnoea), orthopnoea, paroxysmal nocturnal dyspnoea, fatigue, symptoms secondary to
                 pulmonary oedema e.g. cough, haemoptysis, wheeze.
                 On Examination:
                 Most common signs: tachycardia, basal crackles (patient should cough, to make sure it is
                 pulmonary oedema), Gallup rhythm (a third heart sounds and/or a fourth heart sound).
                 Less common signs: tachypnoea, cardiomegaly, peripheral cyanosis, pleural effusion, pulsus
                 alternans (alternating of large and small pulse pressures).
   Similar
 symptoms/
other disease
Investigations   Chest radiology, ECG, Echocardiography, biochemistry, haematology and urinalysis
T    Surgical
r Pharmaco
e cological
a   Non-       Acute: Principles are outlined here. Lung function optimisation (sit the patient up,
t Pharmaco     administer maximal oxygen concentration), Intravenous diuretics (40-80mg of furosemide),
m  logical     Intravenous opiate analgesia (5mg diamorphine over 5 min), treatment of arrhythmias (may
e              require DC cardioversion or intravenous anti-arrhythmic therapy), vasodilator therapy
n              (GTN, Sodium nitroprusside), digoxin (cautious intravenous administration if the above fail),
t              Inotrope (dobutamine infusion (inotrope 2.5-10mcg/kg/minute, titrate against response),
               dopamine (selective renal vasodilator, initial dose 2mcg/kg/minute)

   Disease     Congestive cardiac failure (heart failure Pg 733)
Epidemiology       Worldwide prevalence of heart failure is variable, but increases with age.
                   E.g in Scotland, prevalence is 7.1 per 1000 but this rises to 90.1 in 1000 over the age
                       of 85.
                   In the UK the incidence is about 2%
                   Approximately 23 million people worldwide have HF.
                   Prognosis has improved, but mortality rate is still high with approximately 50% of
                       patients dead in 5 years.
                   Costs of HF are in excess of £1 billion per year (5 % of admissions)
 Pathology         Can result from any structural or functional cardiac disorder that impairs the hearts
                       ability to function as a pump.
                   Coronary artery disease is the most common
               Changes due to HF:
                   Ventricular dilation
                   Myocyte hypertrophy
                   Increased collagen synthesis
                   Altered myosin gene expression
                   Salt and water retention
                   Sympathetic stimulation
                   Peripheral vasoconstriction
                   others
Aetiology/RF   Causes:
                   Ischaemic heart disease (35-40%)
                   Cardiomyopathy (dilated) (30-34%)
                   Hypertension (15-20%)
                   Valvular heart disease
                   Congenital heart disease
                   Alcohol and drugs
                   Others (see table 13.19 pg 734)
   Signs/          Many causes of acute HF, or more insidiously with chronic heart failure.
 symptoms          Different causes can create left ventricular systolic dysfunction (often ischaemic
                       disease, but can also be valvular and hypertension)
                   Right ventricular systolic dysfunction (may be secondary to LVSD but has other
                       causes e.g. RV infarction, pulmonary hpt)
                   Diastolic HF signs and symptoms of HF with preserved LV ejection fraction above
                       45-50%, and abnormal relaxation causing impairment of diastolic LV filling- most
                       common in elderly hypertensive patients)
               Symptoms:
                   Exertional dyspnoea
                   Orthopnoea
                   Paroxysmal nocturnal dyspnoea
                   Fatigue
                 Signs:
                      Cardiomegaly
                      3rd/4th heart sounds
                      Elevated JVP
                      Tachycardia
                      Hypotension
                      Bi-basal crackles
                      Pleural effusion
                      Ankle oedema
                      Ascites
                      Tender hepatomegaly
                 NOTE: Know the New York Heart Association’s classifications of HF- Pg 736 table 13.21.
   Similar
 symptoms/
other disease
Investigations         Blood tests
                       Chest X-ray (cardiomegaly, pulmonary congestion with upper lobe diversion, fluid in
                        fissures, Kerley B lines and pulmonary oedema)
                     Electrocardiogram
                     ECG
                     Stress ECG
                     Nuclear cardiography
                     CMR- cardiac MRI
                     Cardiac catheterization
                     Cardiac biopsy (for diagnosis of cardiomyopathies)
                     Cardiopulmonary exercise testing
                     Ambulatory 24hr ECG monitoring
T    Surgical        Revascularisation- coronary artery disease is the most common cause.
r                    Hibernating myocardium and myocardial stunning- myocardium that will recover
e                       from chronic coronary artery disease (pg 740)
a                    Bi-ventricular pacemaker or implantable cardioverter-defibrillator
t                    Cardiac transplantation.
m Pharmaco           Diuretics- ACE, Angiotensin II receptor antagonists, calcium channel blockers
e   cological        Beta blockers- aldosterone antagonists, cardiac glycosides (digoxin), Vasodilators
n                       and nitrates, inotropic and vasopressor agents
t                    Prophylatic anticoagulation
       Non-          Lifestyle advice- education, obesity control, dietary modification (smaller meals, less
   Pharmaco             salt), smoking cessation.
      logical        Physical activity, exercise and rehabilitation
                     Vaccination against pneumococcal disease and influenza
More info on Acute HF on page 742
   Disease       Diabetes mellitus Type 1 Pg 1032
Epidemiology         Peak age of incidence is puberty, but can present at any age.
                     Highest rates in Finland and northern European countries with the exception of
                        Sardinia (for some unknown reason has the second highest incidence in the world).
                     Rates increasing- by about 2-3% and is most marked in children under 5 years of
                        age.
                     WHO states that there are currently 19.4 million people with type 1 diabetes and
                        this is predicted to reach 57.2 million by 2025.
  Pathology          Disease of insulin deficiency, almost all patients have the immune mediated form of
                        the disease (type 1A).
                     Type with slower progression into insulin deficiency occurs in later life and is called
                      a ‘slow burning’ variant in later life sometimes called latent autoimmune diabetes in
                      adults (LADA) and may be difficult to distinguish from type 2 diabetes.
                     Belongs to a family of HLA-associated immune mediated organ specific diseases.
                      Genetic susceptibility is polygenic, with the greatest contribution from the HLA
                      region.
                     Autoantibodies can be detected in the first few years of life against pancreatic islet
                      constituents and predate clinical symptoms by several years (autoantibodies also
                      found in those with LADA).
Aetiology/RF   Causes:
                   Genetic susceptibility and inheritance- increased susceptibility is inherited, but the
                       disease in not genetically predetermined. Non-genetic factors must also be involved.
                       Risk is greater with diabetic father than mother. HLA system- genes on chromosome
                       6 are very polymorphic and modulate the autoimmune response system of the body.
                       There are also other genes/ gene regions that affect the likelihood of a person
                       developing diabetes
                   Overlaps with other organ specific autoimmune diseases including autoimmune
                       thyroid disease, coeliac disease, addisons disease and pernicious anaemia.
                   Environmental factors- Islet antibodies appear in the first few years of life,
                       suggesting prenatal or early postnatal interactions with the environment. Exposure
                       to dietary constituents, enteroviruses (such as coxsackie B4) or vaccinations has
                       often been suspected but their role is yet to be confirmed. Also has been suggested
                       that a cleaner environment and less early stimulation of the immune system may be
                       to blame.
   Signs/          Hyperglycaemia, which fails to correct with diet and tablet treatment and
 symptoms              autoantibody tests confirming autoimmune disease.
               Acute- Young people present with a 2-6 week history and report the classic triad of
               symptoms:
                   Polyuria- due to osmotic diuresis that results when blood glucose levels exceed the
                       renal threshold
                   Thirst- due to the resulting loss of fluids and electrolytes
                   Weight loss- due to fluid depletion and the accelerated breakdown of fat and muscle
                       secondary to insulin deficiency
                   Additionally, ketonuria is often present in young people and may advance to
                       ketoacidosis if the early symptoms are not recognized and treated.
               Subacute- Onset may be over several months or years, particularly in older patients.
                   Thirst
                   Polyuria
                   Weight loss
                   Additionally patient may complain of lack of energy, visual blurring (glucose-
                       induced changes in refraction) or pruritus valvulae (vulval itch) or balanitis
                       (inflammation of head of the penis) due to candida infection.
               Complications of the presenting feature:
                   Staphylococcal skin infections
                   Retinopathy noted during a visit to the optician
                   Polyneuropathy causing tingling and numbness in the feet
                   Erectile dysfunction
                   Arterial disease, resulting in MI or peripheral gangrene
               Asymptomatic diabetes:
                   Glycosuria (not diagnostic but points to need for further tests- present in 1% of
                       population naturally)/ raised blood glucose may be detected on routine
                       examination.
                 Physical examination:
                     Evidence of weight loss and dehydration and the breath may smell of ketones
                     Older patients may present with established complications such as retinopathy
                     May be signs of illness that is causing secondary diabetes in some cases.
                     Severe insulin resistance may lead to acanthosis of nigrans (blackish pigmentation of
                        the nape of the neck and axillae).
                 Complications of diabetes pg 1049.
   Similar
 symptoms/
other disease
Investigations         Easy to diagnose when overt symptoms are present, and glucose tolerance test is
                        hardly ever useful for clinical purposes (is useful for epidemiological studies).
                     Glucose monitoring using pin prick method.
                     Impaired glucose tolerance test (IGT)- risk factor for future diabetes and
                        cardiovascular disease. Obesity and lack of regular physical exercise make frank
                        diabetes more likely.
                     Impaired fasting glucose (fasting plasma glucose between 6.1 and 6.9 mmol/l). Used
                        to avoid IGT and is once again a predictor of frank diabetes and cardiovascular
                        disease.
                 No other tests are needed to diagnose diabetes, however you can:
                     Screen urine for protein, do a FBC, U and E’s, LFT’s and random lipids.
T  Surgical
r Pharmaco             INSULIN! – Always indicated in those who have been in ketoacidosis and is usually
e cological             indicated in lean patients who present under the age of 40 years (look it up- pg
a                       1042).
t                      Insulin alternatives such as Exanatide- Given by subcutaneous injection, promotes
m                       insulin release, inhibits glucagon release, reduces appetite and delays gastric
e                       emptying. Side effects include nausea and acute pancreatitis.
n                      Drugs to encourage weight loss, if patient is overweight such as orlistat, acarbose etc
t                       (look under type 2 as this affects type 2 more).
     Non-              Education about weight and risks of developing diabetes
  Pharmaco             Patient education and cooperation in their treatment to control their own glycaemic
    logical             levels.
                       Smoking cessation
                       Monitoring feet
                       Healthy dietary routine (low sugar, high starchy CHO, high in fibre, low in fat)
                       Encouraging exercise
                       Support to patients, allowing them to cope with the psychosocial implications of
                        diabetes.

   Disease       Diabetes Type 2 Pg 1033
Epidemiology         Relatively common in all populations enjoying an affluent lifestyle
                     Overall prevelance in UK is 2-3% and the lifetime risk is 15%
                     2-4 times more prevalent in south Asian, African and Caribbean ancestry who live in
                        the UK and the lifetime risk in these groups exceeds 30%.
  Pathology          The body is no longer able to secrete enough insulin to meet its requirements
                     Plus the insulin is less able to bind to its receptor due to ‘insulin resistance’.
                     Despite circulating insulin levels being higher than healthy individuals, there is
                        increased glucose production in the liver (inadequate suppression of
                        gluconeogenesis due to insulin resistance) and decreased glucose uptake by
                        peripheral cells. Hyperglycaemia and lipid excess may be toxic to Beta cells and so
                        may advance the disease.
Aetiology/RF   Links/RF:
                   Age
                   Obesity (increases risk 80-100 fold)
                   Ethnicity
                   Family history
                   Pregnancy can accelerate development of illness
                   Hypertension
                   Hypertriglycerdaemia
                   Decreased HDL cholesterol
                   Disturbed haemostatic variables and increased in pro inflammatory markers
               Causes:
                   Genetic
                   Environment (both early and late)- low birth weight and at 12 months old has been
                       linked to glucose intolerance in later life and weight gain in later life is also linked.
                   Immunology and inflammation- no evidence of immune involvement, but some carry
                       islet autoantibodies and these patients are more likely to go on to regress into
                       insulin therapy (likely to be type one masquerading as type 2).
                   Decreased production of insulin, and increased resistance by the body to insulin’s
                       effects.
   Signs/          May be subclinical/undiagnosed for years before diagnosis, with 25-50% patients
 symptoms              showing some evidence of vascular complications at the time of diagnosis.
                   Raised CRP
               Acute- Young people present with a 2-6 week history and report the classic triad of
               symptoms:
                   Polyuria- due to osmotic diuresis that results when blood glucose levels exceed the
                       renal threshold
                   Thirst- due to the resulting loss of fluids and electrolytes
                   Weight loss- due to fluid depletion and the accelerated breakdown of fat and muscle
                       secondary to insulin deficiency
                   Additionally, ketonuria is often present in young people and may advance to
                       ketoacidosis if the early symptoms are not recognized and treated.
               Sub-acute- Onset may be over several months or years, particularly in older patients.
                   Thirst
                   Polyuria
                   Weight loss
                   Additionally patient may complain of lack of energy, visual blurring (glucose-
                       induced changes in refraction) or pruritus valvulae (vulval itch) or balanitis
                       (inflammation of head of the penis) due to candida infection.
               Complications of the presenting feature:
                   Staphylococcal skin infections
                   Retinopathy noted during a visit to the optician
                   Polyneuropathy causing tingling and numbness in the feet
                   Erectile dysfunction
                   Arterial disease, resulting in MI or peripheral gangrene
               Asymptomatic diabetes:
                   Glycosuria (not diagnostic but points to need for further tests- present in 1% of
                       population naturally)/ raised blood glucose may be detected on routine
                       examination.
               Physical examination:
                   Evidence of weight loss and dehydration and the breath may smell of ketones
                   Older patients may present with established complications such as retinopathy
                   May be signs of illness that is causing secondary diabetes in some cases.
                       Severe insulin resistance may lead to acanthosis of nigrans (blackish pigmentation of
                        the nape of the neck and axillae).
                 Complications of Diabetes- pg 1049
   Similar
 symptoms/
other disease
Investigations          Easy to diagnose when overt symptoms are present, and glucose tolerance test is
                         hardly ever useful for clinical purposes (is useful for epidemiological studies).
                      Glucose monitoring using pin prick method.
                      Impaired glucose tolerance test (IGT)- risk factor for future diabetes and
                         cardiovascular disease. Obesity and lack of regular physical exercise make frank
                         diabetes more likely.
                      Impaired fasting glucose (fasting plasma glucose between 6.1 and 6.9 mmol/l). Used
                         to avoid IGT and is once again a predictor of frank diabetes and cardiovascular
                         disease.
                 No other tests are needed to diagnose diabetes, however you can:
                      Screen urine for protein, do a FBC, U and E’s, LFT’s and random lipids.
T  Surgical           Diabetes may even be reversed by the use of bariatric surgery, to be used in those
r                        with marked obesity that are unresponsive to 6 months intensive attempts at dieting
e                        and graded exercise. Risks need to be weighed against the benefits. About a third of
a                        patients become non-diabetic after gastric bypass.
t Pharmaco       Diet and lifestyle changes are key to controlling type 2 diabetes, and no amount of
m cological      medication will succeed where these have failed. Tablets are however needed if
e                unsatisfactory metabolic control is achieved within 4-6 weeks. 3 options:
n                     Metformin (biguanide)- remains the best validated primary treatment for type 2
t                        diabetes. Reduces the rate of gluconeogenesis, hence hepatic glucose output and
                         increases insulin sensitivity. Does not affect insulin output, or predispose to
                         hypoglycaemia or weight gain. Shown to reduce cardiovascular risk. Adverse effects
                         include anorexia, epigastric discomfort and diarrhea. Not to be used if patient has
                         lactic acidosis. Can defer the onset of type 2 diabetes.
                      Sulfonylureas (gliclazide)- promote insulin release, ineffective in those with
                         decreased beta cell mass and avoided during pregnancy. Cheap and allow short-term
                         control (1-3 years) but effect wears off as beta cell levels drop off (due to glucose
                         toxicity). May cause weight gain and can cause hypoglycaemia (tolbutamide is safest
                         in elderly due to short duration of action).
                      Thiazolidinediones (known as glitazones): Reduces insulin resistance. Fatty tissue
                         redistribution occurs, reducing central adiposity but increasing peripheral fat.
                         Reduce circulating insulin levels relative to plasma glucose, but do not return
                         glucose levels back to normal. Can be used alone or with other agents. Side effects
                         may be weight gain, fluid retention (increased risk of HF), anaemia and osteoporosis.
                 Other useful therapies:
                      INSULIN! - to be given to account for increasingly lowered response to the bodies
                         insulin, will be needed at higher quantities as the beta cells become affected and
                         decrease in number (pg 1041).
                      Exanatide- alternative to insulin. Given by subcutaneous injection, promotes insulin
                         release, inhibits glucagon release, reduces appetite and delays gastric emptying. Side
                         effects include nausea and acute pancreatitis.
                      Orlistat to aid weight loss
                      Intestinal enzyme inhibitors such as acarbose which decrease CHO absorption
                      Rimonobant- encourages weight loss in those with type 2 diabetes.
     Non-             Diabetes may even be reversed by a vast change in diet
   Pharmaco           Education about weight and risks of developing diabetes
    logical           Patient education and cooperation in their treatment to control their own glycaemic
                      levels.
                     Smoking cessation
                     Monitoring feet
                     Healthy dietary routine (low sugar, high starchy CHO, high in fibre, low in fat)
                     Encouraging exercise
                     Support to patients, allowing them to cope with the psychosocial implications of
                      diabetes.

   Disease     Hypothyroidism pg 985
Epidemiology        One of the most common endocrine conditions in the UK, with a prevalence of over
                      1% in women, but under 0.1% in men.
                    Lifetime prevalence is higher- 9% for women and 1% for men with the mean age at
                      diagnosis being 60 years.
                    Worldwide presence of subclinical hypothyroidism varies from 1-10%.
 Pathology          Under activity of the thyroid is usually primary, from disease of the thyroid but may
                      be secondary to hypothalamic-piuitary disease (reduced TSH drive).
Aetiology/RF   Causes of primary hypothyroidism:
               1) Automimmune:
                    Atrophic (autoimmune) hypothyroidism- most common cause of hypothyroidism
                      and is associated with antithyroid autoantibodies leading to lymphoid infiltration of
                      the gland and eventual atrophy and fibrosis. 6 times more common in women and
                      incidence increase with age. Associated with pernicious anaemia, vitiligo, and other
                      endocrine deficiencies.
                    Hashimotos thyroiditis- another form of autoimmune disease as also more common
                      in women and is most common in late middle age. Produces atrophic changes with
                      regeneration leading to goitre formation. Pts may be hypo or euthyroid, though they
                      may go through an initial toxic phase ‘hashi-toxicity’. Levothyroxine may shrink the
                      goiter even when the pt is not hypo.
                    Postpartum thyroiditis- transient phenomenon following pregnancy. May cause
                      hypo or hyperthyroidism or the two sequentially. Believed to be due to
                      modifications in immune system necessary in pregnancy and is histologically a
                      lymphocytic thyroiditis. Usually self limiting but may progress into hypothyroidism.
                      May be misdiagnosed as postnatal depression.
               2) Defects of hormone synthesis:
                    Iodine deficiency- dietary iodine deficiency does still exist, with endemic goitre
                      being present in some places commonly. May be hypo or euthyroid depending on
                      severity of iodine deficiency. Method is thought to be bordering hypo, with TSH
                      stimulation and thyroid enlargement as a result of iodine deficiency. Affects Russia,
                      India, East Asia.
                    Dyshormonogenesis- rare condition. Due to genetic defects in the synthesis of
                      thyroid hormones patients develop hypothyroidism and goitre. One particular form
                      is associated with sensorineural deafness.
                   3) Infective- post-subacute thyroiditis
                   4) Tumour
                   5) Post surgery/ post irradiation
                   6) Congenital- agenesis/ ectopic thyroid remnants
                   7) Drug side effects (eg lithium, amiodarone, interferon)
               Secondary causes- hypopituitarism, peripheral resistance to thyroid hormone
   Signs/      Symptoms:
 symptoms           Constipation
                    Weight gain
                    Cold intolerance (poor perfusion)
                      Tiredness
                      goitre
                 Signs:
                      Myxoedema refers to the accumulation of mucopolysaccharide in subcutaneous
                          tissues
                      Mental slowness- psychosis/dementia/ataxia/deafness/poverty of movement
                      Loss of eyebrows
                      Hypertension
                      Carpal tunnel syndrome
                      Slow relaxing reflexes
                      Dry haired/ dry thick skin
                      Deep voice
                      Bradycardia
                      Depression (especially in elederly can be called ‘myxedema madness’- pg 987
                      Worst case- elderly present with confusion or even coma.
                 Milder symptoms are harder to diagnose and distinguish from other causes of non-specific
                 tiredness.
                      Children may not show classic features but may have slow growth, poor school
                          performance or arrest at pubertal development.
                      Young women may show no obvious signs.
                      Elderly may not show any different signs than those expected with normal ageing.
                 Full list of symptoms on pg 986
   Similar
 symptoms/
other disease
Investigations         Serum TSH (high confirms primary hypothyroidism)
                       A low free T4 level suggests the hypothyroid state
                       Anaemia- normochromic an normocytic (may be macro or microcytic though)
                       Increased serum aspartate transferase levels from muscle/liver
                       Increased serum creatine kinase levels with associate myopathy
                       Hypercholesterolaemia and hypertriglyceridaemia
                       Hyponatraemia due to increased ADH and impaired free water clearance.
T  Surgical            Perhaps removal of any secondary causes- eg tumour.
r Pharmaco             Levothyroxine (thyroxine/ T4) replacement therapy. Starting dose depends on
e cological             severity of deficiency, age and fitness of patient (especially their cardiac output).
a                       Monitoring of T4 levels also takes place, and levels of TSH in blood are a good
t                       indicator of the need for more levothyroxine. TSH levels should not be completely
m                       suppressed because of the increased risks of osteoporosis and AF. Clinical
e                       improvement may take 2 weeks or more, and full resolution may take 6 months.
n                       Should also check for other endocrine diseases developing such as addisons disease/
t                       pernicious anaemia.
     Non-              Screening for congenital hypothyroidism (1/3500 births). If left it causes permanent
  Pharmaco              neurological and intellectual damage (cretinism). Routine screening of blood spot
    logical             (Guthrie test) to detect high TSH levels is efficient and cost effective as cretinism can
                        be avoided if T4 is given within the first few months of life.

   Disease       Hyperthyroidism (thyroid overactivity, thyrotoxicosis) pg 987
Epidemiology         Common, affecting 2-5% of all females at some time most often between the ages of
                        20-40
                     Affects females more than males with a ratio of 5:1
  Pathology          Nearly all causes (>99%) are caused by intrinsic thyroid disease- a pituitary cause is
                        extremely rare.
Aetiology/RF     Causes:
                 1) Graves disease:
                 Most common cause of hyperthyroidism, due to an autoimmune process. Serum IgG
                 antibodies bind to TSH receptors in the thyroid, stimulating thyroid hormone production (i.e
                 they behave like TSH). The autoantibodies are present in 85-90% of cases of graves disease
                 (are also specific to graves disease) and levels decline with treatment. It is likely that there is
                 some genetic condition, however an environmental trigger may be needed in the form of E.
                 Coli or other Gram negative organisms that contain TSH binding sites. Also linked with other
                 autoimmune diseases such as pernicious anaemia, vitiligo and myasthenia gravis. Only 40%
                 of patients have only one episode, most have a relapsing remitting pattern.
                 2) Solitary toxic adenoma/nodule- This is the cause of about 5% of cases of
                 hyperthyroidism. It does not usually remit after a course of antithyroid drugs.
                 3) Toxic multinodular goitre- This commonly occurs in older women, and once again
                 antithyroid drugs are rarely successful at inducing a remission, although they can control
                 the hyperthyroidism.
                 4) De Quervains thyroiditis- Transient form of hyperthyroidism from an acute inflammatory
                 process, probably viral in origin. Apart from toxicosis, there is usually fever, malaise and
                 pain in the neck with tachycardia and local thyroid tenderness. TFT’s show initial
                 hyperthyroidism, the ESR and plasma viscosity are raised. Hypothyroidism, usually
                 transient may then follow after a few weeks. Treatment of the acute phase is with aspirin,
                 using prednisolone in severely symptomatic cases.
                 5) Postpartum thyroiditis
                 6) Amiodarone induced thyrotoxicosis- Amiodarone (antiarrythmic drug) causes two types.
                 Type 1 is associated with pre existing graves disease and type 2 is not associated with any
                 previous thyroid disease.
   Signs/        Symptoms:
 symptoms             Weight loss
                      Increased appetite
                      Tremor
                      Heat intolerance
                      Oligomenorrhoea (Infrequent, light periods)
                     
                 Signs:
                      Thyroid eye disease
                      Graves disease- graves dermopathy, lymphadenopathy and splenomegaly may occur
                          in rare cases.
                      Hyperreflexia
                      Tachycardia/ AF
                      Full pulse
                      Exopthalmos
                      Warm vasodilated peripheries
                      Lid lag and stare
                      Palmar erythema
                      Thyroid acropachy
                 Full list pg 988
   Similar            Mild hyperthyroidism can get confused with anxiety
 symptoms/
other disease
Investigations          Serum TSH is suppressed in hyperthyroidism except for the very rare cases of TSH
                         hypersecretion
                        Raised free T3 or T4 confirms the diagnosis
                        TPO and thyroglobin antibodies are present in most cases of graves disease.
T  Surgical          Subtotal thyroidectomy- only performed in patients who have previously been
r                     rendered as euthyroid. Carries risks- damage to laryngeal nerve, risk of becoming
e                     hypothyroid etc.
a Pharmaco     Antithyroid drugs:
t cological        Carbimazole/ propylthiouracil. Inhibit the formation of thyroid hormones, also
m                     slightly immunosuppressive. 50% of patients relapse after a course, mostly within
e                     the first two years. May be toxic (causing agranulocytosis)
n                  Can be used to gradually suppress thyroid to correct levels, or can use the ‘block and
t                     replace’ method- carbimazole is used in levels that suppress the thyroid completely
                      and levothyroxine is given to provide T4 levels.
                   Radioactive Iodine is also given- accumulates in the thyroid and destroys the gland
                      by local radiation- takes several months to be fully effective. Risks of neck
                      discomfort and worsening hyperthyroidism etc. Debates about risk of
                      carcinogenesis.
               Symptom relief:
                   Beta blockers to control tachycardia (and decreases peripheral conversion of T3 to
                      T4)
     Non-
   Pharmaco
    logical

   Disease     Goitre (thyroid enlargement) pg 992 (includes thyroid nodules)
Epidemiology        More common in women than men
                    Goitres are present on examination in up to 9% of the population
 Pathology          Can be either physiological or pathological
Aetiology/RF   Causes:
                    Physiological- puberty/pregnancy
                    Autoimmune- graves disease, hashimoto’s disease
                    Thyroiditis (de Quervain’s thyroiditis)
                    Iodine deficiency
                    Dyshormonogenesis
                    Excessive doses of carbimazole or propylthiouracil will induce goitre
                    Nodular- multinodular goitre/ solidary nodular/ fibrotic (reidel’s thyroiditis)/cysts
                    Tumours- Adenomas/carcinoma/lymphomas
                    Sarcoidosis
                    TB
   Signs/           Goitre can often be seen, it is noted as a cosmetic defect by the patient or by
 symptoms              friends/relatives
                    Majority are painless/ however some acute varieties may be painful
                    Large goiters can produce dysphagia and difficulty in breathing, implying
                       oesophageal/ tracheal compression.
                    May be more visible than palpable (if small)
                    Clinical examination should record the size, shape, consistency and mobility of the
                       gland as well as whether its lower margin can be demarcated (thus implying the
                       absence of retrosternal extension).
                    A bruit may be present
                    Associated lymph nodes should besought and the tracheal position determined if
                       possible
                    Notes on medication (esp those containing iodine and and radiation contact)
                    Puberty and pregnancy may produce a diffuse increase in the size of the thyroid
                    Pain in goitre may be caused by thyroiditis, bleeding into a cyst or (rarely) a tumour
               Nodular goitres:
                       Multinodular goitre- most common of the nodular goiters, especially in older
                        patients. Usually Euthyroid but may be hyperthyroid or borderline with suppressed
                        TSH levels but normal T3 and T4. Most common cause of tracheal and oesophageal
                        compression and can cause laryngeal nerve palsy. May extend retrosternally.
                       Solidary nodular goitre- presents a difficult problem at diagnosis. Malignancy should
                        be considered in any solidary nodule- however the majority are cystic or benign
                        (and in fact just by far the largest of multinodular goitre). See more info under
                        surgical considerations and FNA.
                       Fibrotic goitre- Reidel’s thyroiditis is a rare condition, often producing a ‘woody
                        gland’. Associated with other midline fibrosis and is often difficult to distinguish
                        from carcinoma, being irregular and hard.
   Similar
 symptoms/
other disease
Investigations         FBC/ TFT’s/ Thyroid antibodies
                       USS
                       Chest and thoracic inlet X-rays- can detect tracheal compression and large
                        retrosternal extensions
                       Fine needle aspiration (FNA)- in patients with a solitary nodule (5% chance of
                        malignancy)
                       Thyroid scan- shows likelihood of nodules being malignant or not
T  Surgical            If there is a possibility of malignancy- rapid growth, pain, cervical lymphadenopathy,
r                       change in voice or previous irradiation to the neck are worrying features. Positive or
e                       suspicious FNA makes surgery mandatory. More info- pg 993
a                      Pressure symptoms on the trachea (or more rarely oesophagus)
t                      Cosmetic reasons if it is a large goitre.
m Pharmaco
e cological
n    Non-              If patient has euthyroid goitre and it is small with no symptoms then it can be
t Pharmaco              monitored (esp during puberty/pregnancy as it is likely it will resolve itself
    logical             spontaneously)

   Disease       Cushing’s syndrome pg 1012
Epidemiology
 Pathology             Clinical state of increased free circulating glucocorticoid.
                       Occurs most often following the therapeutic administration of synthetic steroids or
                        ACTH.
                       All the spontaneous forms are rare (<5 cases per million per year)
Aetiology/RF     Causes:
                     ACTH dependent disease- Pituitary dependent (Cushing’s disease), Ectopic ACTH
                         producing tumours, ACTH administration.
                     Non- ACTH causes- Adrenal adenomas, adrenal carcinomas, Glucocorticoid
                         administration
                     Others- Alcohol-induced pseudo- Cushing’s syndrome
   Signs/        Symptoms:
 symptoms            Weight gain (central)
                     Depression
                     Insomnia
                     Poor libido
                     Growth arrest in children
                     Polyuria/polydipsia
                     Psychosis
                         Muscular weakness
                         Thin skin/easy bruising
                 Signs:
                         Moon face
                         Plethora
                         Thin skin
                         Bruising
                         Hypertension
                         Pathological fractures (especially vertebrae and ribs)
                         Striae (purple or red)
                         Proximal myopathy
   Similar
 symptoms/
other disease
Investigations           48 hour low-dose dexamethasone test
                         24 hour urinary free cortisone measurements
                         Circadian rhythm (after 48hours in hospital cortisol samples are taken)
                         Other tests- insulin stress test, desmopressin stimulation test and CRH tests.
                         Adrenal CT or MRI scan- to find a tumour
                         Pituitary MRI
                         Plasma K+ levels
                         High- dose dexamethasone test
                         Plasma ACTH levels
                         CRH test
                         Chest X- ray
T  Surgical              Trans-sphenoidal removal of a tumour (pituitary dependent hyperadrenalism).
r                        Bilateral adrenalectomy (see nelsons syndrome).
e                        Adrenal adenoma resectioning
a                        Tumours secreting ACTH ectopically should be resected is possible
t Pharmaco               Metyrapone and ketoconazole- given to stop cortisol hyper secretion before any
m cological               other treatment (eg surgery) can take place.
e                        External pituitary irradiation (tumour)
n    Non-
t Pharmaco
    logical

   Disease       Iron deficiency anaemia Pg 393/ 395
Epidemiology          Most common cause of anaemia in the world, affecting 30% of the world’s
                         population- equivalent to 500 million people.
  Pathology           Often due to bodies limited ability to absorb iron and the frequent loss of iron owing
                         to haemorrhage (most iron eaten is in its insoluble ferric form, which has poor
                         bioavailablity).
                      Linked to microcytic anaemia (however this can also be caused by anaemia of
                         chronic disease, sideroblastic anaemia and thalassaemia).
Aetiology/RF     Causes:
                      Blood loss! (Most common from uterus or GI tract-hookworm infestation)
                      Poor dietary intake of iron
                      Increased demands- such as growth and pregnancy
                      Decreased absorption (eg postgastrectomy)
                      NSAIDS- may give rise to GI bleeds
   Signs/             My be asymptomatic
 symptoms        Signs (for any form of anaemia):
                      Pallor
                      Tachycardia
                      Systolic flow murmur
                      Cardiac failure
                 Signs for iron deficiency anaemia:
                      Koilonychia
                      Brittle nails
                      Atrophy of the papillae of the tongue
                      Angular stomatitis
                      Brittle hair
                      A syndrome of dysphagia and glossitis (Plummer-Vinson/ Paterson-Brown-Kelly
                         syndrome)
                 Symptoms (all non-specific):
                      Fatigue, headaches and faintness are all very common
                      Breathlessness
                      Angina
                      Intermittent claudication
                      Palpitations

   Similar             Thalassaemia
 symptoms/             Sideroblastic anaemia
other disease          Anaemia of chronic disease
Investigations         Blood count and film
                       Serum iron an iron- binding capacity
                       Serum ferritin
                       Serum soluble transferrin receptors
                       Bone marrow
                       Other investigations
T  Surgical
r Pharmaco             Oral iron- ferrous Sulphate (200mg three times daily) is often all that is needed
e cological            Parenteral iron (deep IM injections) of iron- sorbitor for those who do not respond
a                       well to oral iron.
t    Non-
m Pharmaco
e   logical
n
t

   Disease       Macrocytic anaemia Pg 397
Epidemiology
 Pathology       Can be split into megaloblastic and non-megaloblastic types, depending on bone marrow
                 findings.
                 Megaloblastic:
                      Characterized by erythroblasts in the bone marrow with delayed nuclear maturation
                         because of defective DNA synthesis (megaloblasts)
Aetiology/RF     Causes of megaloblastic:
                      Vitamin B12 deficiency or abnormal B12 metabolism
                      Folic acid deficiency or abnormal folate metabolism (many- dietary, anorexia,
                         pregnancy, malabsorbtion etc page 400)
                      Other defects in DNA synthesis, e.g. congenital enzyme deficiencies
                      Myelodysplasia due to dyserythropoiesis
                 Causes of B12 deficiency:
                      Low dietary intake- vegans
                      Impaired absorption
                      Stomach- pernicious anaemia, gastrectomy, congenital deficiency of intrinsic factor
                      Small bowel- ilieal disease/resection, bacterial overgrowth, tropical sprue, fish
                         tapeworm
                      Others
                 Other causes of macrocytic anaemia (not just megaloblastic):
                      Alcohol excess/ liver disease
                      Reticulocytosis
                      Cytotoxics (hydroxycabamide)
                      Marrow infiltration
                      Myelodysplastic syndromes
                      Hypothyroidism
                      Antifolate drugs- phenytoin.
   Signs/             My be asymptomatic
 symptoms        Signs (for any form of anaemia):
                      Pallor
                      Tachycardia
                      Systolic flow murmur
                      Cardiac failure
                 Symptoms (all non-specific):
                      Fatigue, headaches and faintness are all very common
                      Breathlessness
                      Angina
                      Intermittent claudication
                      Palpitations
                 Pernicious anaemia and Folate deficiency- neurological symptoms
   Similar
 symptoms/
other disease
Investigations         FBC- Anaemia with large MCV, peripheral blood film shows oval macrocytes with
                        hypersegmented polymorphs with six or more lobes in the nucleus. If severe there
                        may be leucopenia and thrombocytopenia.
                       Further investigations to determine which type of anaemia is present.
T  Surgical
r Pharmaco             Hydroxocobalamin can be given IM for B12 deficiency
e cological            Folic acid can be given daily to treat Folate deficiency
a    Non-
t Pharmaco
m   logical
e
n
t

   Disease       Osteoarthritis Pg 518
Epidemiology         Most common form of arthritis
                     Prevalence increases with age and most people over the age of 60 will show some
                        radiological evidence (not all will show symptoms).
                     There is a higher incidence in women
  Pathology          Occurs in synovial joints and is characterized by cartilage loss with accompanying
                        periarticular bone response
                       The whole joint structure including cartilage, subchondral bone, ligaments, menisci,
                        synovium and capsule is involved.
                      Pathologically there is inflammation to the articular and periarticular bones and
                        alterations in cartilage structure.
                      Different clinical subsets- localized OA, Nodal OA, Hip OA, Knee OA, Primary
                        generalized OA, Erosive OA, Crystal associated OA (see page 521)
Aetiology/RF          May be no known cause
                      Genetic predisposition
                      Obesity
                      Hypermobility
                      Osteoporosis
                      Trauma
                      Congenital joint dysplasia
                      Joint congruity
                      Occupation
                      Sport/ repetitive use
                      Rheumatoid arthritis
                      Gout
                      Haemophilia
                      Acromegaly
                      Neuropathies
                 More diseases on page 520
   Signs/             Affects many joints, with diverse clinical patterns
 symptoms        Symptoms:
                      Joint pain
                      Joint gelling (stiffening and pain after immobility)
                      Joint instability
                      Loss of function
                 Signs:
                      Joint tenderness
                      Crepitus on movement
                      Limitation of ROM
                      Joint instability
                      Joint effusion and variable levels of inflammation
                      Bony swelling
                      Wasting of muscles
   Similar
 symptoms/
other disease
Investigations         Blood tests- ESR normal CRP may be raised, rheumatoid factor and antinuclear
                        antibodies are negative
                       X-rays Only abnormal when damage is advanced
                       MRI
                       Arthroscopy
                       Aspiration of synovial fluid
T  Surgical            Intra-articular corticosteroid injections produce short term side effects
r                      Replacement athroplasty for knee
e                      Knee replacement
a                      Hip replacement
t Pharmaco             NSAIDS- oral, local gel
m cological            Other analgesia
e      Non-            Weight loss
n    Pharmaco          Exercises to improve muscle strength and stability are useful
t     logical          Hydrotherapy
                       Local heat
                       Acupuncture

   Disease       Gout and hyperuricaemia Pg 536
Epidemiology          Prevalence is increasing mainly in developed countries. In Europe and USA it is
                         approximately 0.2% (hyperuricaemia prevalence is 5%).
                      More common in men (M:F is 10:1)
    Pathology         Uric acid levels start to rise after puberty and are higher in men than women until
                         the menopause. Hyperuricaemia is defined as a serum uric acid level greater than
                         two standard deviations from the mean (420μmol/L in males and 360 μmol/L for
                         females).
                      Most people with hyperuricaemia are asymptomatic even though sodium urate
                         crystals are found in the joints. However osteoarthritic joints are more prone to
                         gouty attacks.
                      Hyperuricaemia results from inadequate renal excretion of uric acid relative to its
                         production and is the major determinant for developing gout
Aetiology/RF     Uric acid levels rise with:
                      Obesity
                      High protein diet
                      High alcohol consumption (particularly beer drinkers)
                      A high fructose intake from fizzy drinks
                      Combined hyperlipidaemia
                      Diabetes mellitus
                      Ischaemic heart disease and hypertension (metabolic syndrome)
                      Family history
                      Impaired excretion of uric acid
                      Chronic renal disease
                      Drug therapy- thiazides, low dose aspirin
                      Increased production of uric acid
                      Hypothyroidism
                      Primary hyperparathyroidism
                      Others- see page 537
      Signs/     Hyperuricaemia causes 4 clinical syndromes:
    symptoms          Acute sodium urate synovitis- gout
                      Chronic polyarticular gout
                      Chronic tophaceous gout
                      Urate renal stone formation
                 Acute gout:
                      Typically presents as a middle aged male with a sudden onset of agonizing pain,
                         swelling and redness of the first MTP joint.
                      Can occur at any time but may be precipitated by too much food/alcohol or
                         dehydration
   Similar            In severe attacks, the overlying crystal cellulitis makes gout difficult to distinguish
 symptoms/               clinically from infective cellulitis
other disease
Investigations         Clinical picture is often diagnostic as is the rapid response to NSAIDS or colchicine.
                       Joint fluid microscopy
                       Serum uric acid levels
                       Serum urea and creatinine
T  Surgical
r Pharmaco       NSAIDS or coxibs rapidly in high doses reduces pain and swelling, any of the below initially
e cological      with food:
a                     Naproven, 750 mg immediately then 500mg every 8-12 hours
t                     Diclofenac 75-100 mg immediately then 50mg every 8-12 hours
m                     Lumiracoxib 100mg daily
e                     Indomethacin 75mg immediately then 50mg every 6-8 hours (gold standard but also
n                        produces side effects)
t                After 24/48 hours initial doses are reduced for a further week
                 Colchicine?
                 Can also use allopurinol to cut down uric acid levels if attacks are frequent, severe (despite
                 dietary changes) or associated with renal impairment. Febuxostat is also available.
     Non-             Dietary advice
   Pharmaco           Cutting down on alcohol consumption
    logical

   Disease       Septic arthritis Pg 539
Epidemiology         Most common organism to cause septic arthritis is Staphylococcus aureus, others
                         include streptococci, other species of staph, Neisseria gonorrhoeae, haemophilus
                         influenza and others in the elderly and RA sufferers.
 Pathology          
Aetiology/RF
   Signs/              Suspected septic arthritis is a medical emergency
 symptoms              In previous fit people, the joint is hot, red, swollen and agonizingly painful and held
                        immobile by muscle spasm.
                       In the elderly an immunosuppressed and in RA the picture is less dramatic, so a high
                        index of suspicion, so a high index of suspicion is needed to avoid missing treatable
                        but potentially severely destructive and occasionally fatal septic arthritis.
                       In 20% the sepsis affects more than one joint
                       Chronic destructive arthritis due to TB is rare
   Similar
 symptoms/
other disease
Investigations         Aspirate the joint and send the fluid for urgent Gram attaining and culture. The fluid
                        is usually frankly purulent. The culture techniques should include those for
                        gonococci and anaerobes.
                       Blood cultures are often positive
                       Leucocytosis is usual, unless the person is severely immunosuppressed
                       X-rays- are of no value in diagnosis of acute septic arthritis
                       Skin wound swabs; sputum and throat swab or urine may be positive and indicate
                        the source of the infection.
T  Surgical            If its an infected prosthesis, it should be removed, the joint capsule filled with
r                       antibiotic-impregnated spacer for 3-6 weeks before a new prosthesis is inserted. The
e                       whole process is covered by antibiotics.
a Pharmaco             Empirical therapy before culture results are obtained- discuss with microbiologist,
t cological             IV flucloxacillin 1-2g 6 hourly plus fusidic acid 500mg orally 8 hourly.
m                      Drainage of the joint and arthroscopic joint washouts are helpful in relieving the
e                       pain.
n                      IV antibiotics should be given for 1-2 weeks
t                      It is useful to give 2 antibiotics to which the organism is sensitive for 6 weeks, then
                        one for a further 6 weeks orally.
                       Analgesics
       Non-           Joint should be immobilized initially and then physiotherapy started early to prevent
    Pharmaco              stiffness and muscle wasting
      logical         Resolution can occur in a few days to weeks, may lead to secondary osteoarthritis
See page 540 for specific examples of bacterial arthritis.

     Disease       Prolapsed Vertebral disk Pg 510 for lumbar disc.
Epidemiology
    Pathology
 Aetiology/RF
      Signs/       See pg 1176 for nerve signs/symptoms
    symptoms
     Similar
   symptoms/
other disease
Investigations
T      Surgical
r Pharmaco
e      cological
a        Non-
 t Pharmaco
m       logical
e
n
 t

   Disease         Depression Pg 1198 (unipolar effective disorder)
Epidemiology            Very common- 5% in the community, with a further 3% having dysthymia (see
                          below)
                        More common in women
                        No increase in age, and no difference with ethnic group or socioeconomic class
                        Married and never married have the same rates, with separated and divorced people
                          having two to three times the prevalence
  Pathology             Depressive disorders or ‘episodes’ are classified as mild, moderate or severe, with or
                          without somatic symptoms
                        Severe depressive episodes are divided according to the presence or absence of
                          psychotic symptoms
                        Dysthymia is a chronic low-grade unipolar depressive illness that lasts for 2 years or
                          more and is characterized by tiredness and low mood, lack of pleasure, low self-
                          esteem and a feeling of discouragement. The mood relapses and remits, with several
                          weeks of feeling well, soon followed by longer periods of being unwell. Can be
                          punctuated by periods of greater severity, so-called ‘double depression’.
Aetiology/RF       Depressive illness is more common in the presence of:
                        Physical diseases, particularly chronic, stigmatizing or painful
                        Excessive and chronic alcohol abuse
                        Social stresses, particularly loss events, such as separation, redundancy and
                          bereavement
                        Interpersonal difficulties with those close to the patient, especially when socially
                          humiliated
                        Lack of social support, with no confiding relationship.
                   Aetiology Pg 1200:
                        Genetic
                        Biochemical
                      Hormonal
                      Neural changes and neuronal growth
                      Sleep
                      Childhood trauma’s and personality
                      Social
                      Stress?
    Signs/        Everyone feels down in the dumps occasionally, however it is when such feelings become
  symptoms        qualitatively different, pervasive or interfere with normal functioning that it has become a
                  depressive illness.
                  Symptoms of ‘major’ depression are below, however marked fatigue and headache are the
                  two most common symptoms and may be the first to appear.
                      Mood- Depressed, miserable, irritable
                      Talk- Impoverished, slow, monotonous
                      Energy- Reduced, lethargic
                      Ideas- Feelings of futility, guilt, self-reproach, unworthiness, hypochondiacal
                          preoccupations, worrying, suicidal thoughts, delusions of guilt, nihilism and
                          persecution.
                      Cognition- Impaired learning, pseudodementia in elderly
                      Physical- Insomnia (esp early waking), poor appetite and weight loss, constipation,
                          loss of libido, erectile dysfunction, bodily pains.
                      Behaviour- retardation or agitation, poverty of movement and expression
                      Hallucinations- Auditory (often hostile, critical)
     Similar
   symptoms/
other disease
Investigations
T      Surgical
r Pharmaco              Antidepressants (tricyclic antidepressants- amitriptyline, selective serotonin
e     cological          reuptake inhibitors- citalopram, MAOi’s- rarely used by anyone other than
a                        psychiatrists)
 t                      Adjunctive drugs (e.g. lithium if no response to two different antidepressants)
m        Non-           Patient needs to know the diagnosis to provide understanding and rationalization of
e Pharmaco               the overwhelming distress inherent in depressive illness- knowing that self-loathing,
n       logical          guilt and suicidal thoughts are caused by their illness can be an ‘antidepressant’ on
 t                       their own.
                        Physical- Stop using depressing drugs (alcohol, steroids), regular exercise,
                         Electroconvulsive therapy
                        Psychological- Education and regular follow up by same Dr, cognitive behavioral
                         therapy, other psychotherapies (couple, family, interpersonal)
                        Social-Financial eligible benefits, debt counseling, Employment change, appropriate
                         secure housing, social neighbours, child care support
                        Most successful is CBT and antidepressants used together.

   Disease        Anxiety (general anxiety disorder- pg 1206)
Epidemiology          This occurs in 4-6% of the population and is more common in women
 Pathology            Mixed anxiety and depressive disorder also exists, where there are equal elements of
                         both.
                      Panic disorder- repeated sudden attacks of overwhelming anxiety, accompanied by
                         severe physical symptoms, usually related to hyperventilation and sympathetic
                         nervous system activity. Often have catastrophic illness beliefs (i.e feel that they will
                         have an MI).
                      Don’t forget phobic disorders (pg 1208)
Aetiology/RF         Genetic (4 X more likely in first degree relatives of affected patients).
   Signs/        Physical symptoms:
 symptoms            Dry mouth, difficulty swallowing, epigastric discomfort, aerophagy,
                     Chest constriction, difficulty inhaling, overbreathing, choking
                     Palpations, awareness of missed beats, chest pain
                     Increased urinary frequency, failure of erection, lack of libido
                     Fatigue, blurred vision, dizziness, sensitivity to noise and/or light, headache, sleep
                        disturbance, trembling
                     Apprehension and fear, irritability, difficulty concentrating, distractibility,
                        restlessness, depersonalization, derealisation.
   Similar           Depressive illness
 symptoms/           OCD
other disease        Presenile dementia
                     Alcohol dependence
                     Drug dependence
                     Benzodiazepine withdrawal
                     Hyperthyroidism
                     Hypoglycaemia
                     Phaechromocytoma
Investigations
T    Surgical
r Pharmaco       Initial drug treatment should involve advice to gradually cease taking anxiogenic drugs such
e   cological    as caffeine and alcohol (rebound anxiety with withdrawal). Drugs medicated can act in two
a                different ways- those that act primarily of the CNS and those that block peripheral
 t               autonomic receptors.
m                     Benzodiazapines- centrally acting anxiolytic drugs that stimulate the release of
e                         GABA. E.g. diazepam. Side effects include sedation and memory problems, and
n                         patients are advised not to drive whilst on treatment. Dependence also can occur.
 t                    Most SSRI’s e.g. fluoxetine are useful symptomatic treatments for general anxiety
                          and panic disorders, as well as some phobias. Treatment response can be delayed
                          several weeks and should last 3 months.
                      Beta blockers (e.g. propanalol) are useful in reducing peripheral symptoms such as
                          palpitations, tremor and tachycardia but do not help with central symptoms such as
                          anxiety.
     Non-             Relaxation techniques can be effective in mild/moderate anxiety e.g. meditation and
   Pharmaco               yoga.
    logical           Anxiety management training- use of verbal cues and mental imagery, the associated
                          anxiety is then reduced by relaxation, distraction and reassuring self-statements.
                      Biofeedback- to show patients they re not relaxed (they fail to realize as they are
                          used to being anxious) e.g. Heart rate
                      Behaviour therapies- most successful is graded exposure (especially for phobias)
                          gradually working up list of phobias until they are cured.
                      Cognitive behavioral therapy- treatment of choice for panic disorder and general
                          anxiety disorder because the therapist and patient identify the mental cues that may
                          provoke anxiety or panic. They then find a different way of looking at situations.


   Disease       Alcohol dependence Pg 1211
Epidemiology          20% of men and 10% of women drink more than double the recommended limits of
                        3 units per day of alcohol for men and 2 units for women.
                      4% of men and 2% of women report alcohol withdrawal symptoms, suggesting
                        dependence.
                     1/5 male admissions on acute wards is directly or indirectly due to alcohol
                     Between 33% and 40% of accident and emergency attenders have blood alcohol
                      concentrations above the present UK legal limit for driving.
 Pathology           Described as a physical dependence on or addiction to alcohol. Term ‘alcoholism is
                      no longer used’ and has been replaced with the term ‘alcohol dependence
                      syndrome’.
                     Dependence is a pattern of repeated self-administration that usually results in
                      tolerance, withdrawal and compulsive drug taking behavior, the essential element of
                      which is the continued use of the substance despite significant substance related
                      problems.
                     Usually occurs after 10 years of heavy drinking (3-4 in women)
                     Delerium tremens- most serious withdrawal state and occurs 1-3 days after alcohol
                      withdrawal, pts are disorientated, agitated and have a marked tremor and visual
                      hallucinations. Signs include sweating, tachycardia, tachypnea and pyrexia.
                      Complications include dehydration, infection, hepatic disease or the Wernicke-
                      Korsakoff syndrome.
Aetiology/RF   Causes:
                   Genetic predisposition
                   Environmental factors- If parents are heavy drinkers.
                   Biochemical factors- several have been suggested, including abnormalities in alcohol
                       dehydrogenase, neurotransmitter substances and brain amino acids such as GABA.
                   Psychiatric illness- uncommon but treatable- some depressed patients drink
                       excessively in the hope of raising their mood
                   Excessive consumption in society- prevalence of alcohol dependence is related to
                       levels of alcohol use in society (along with pricing, laws, availability and social
                       norms)
   Signs/      Should be suspected in any patient presenting with one or more physical problems
 symptoms      commonly associated with excessive drinking (see below). Can also be associated with a
               number of psychiatric illnesses.

               CNS
                    Epilepsy, Wernicke-Korsakoff syndrome, polyneuropathy
               Muscles
                    Acute or chronic myopathy
               CVS
                    Cardiomyopathy, Beriberi heart disease, cardiac arrhythmias, hypertension
               Metabolism
                    Hyperuricaemia (gout), hyperipidaemia, hypoglycaemia, obesity
               Endocrine system
                    Pseudo- Cushings syndrome
               Respiratory system
                    Chest infections
               GI system
                    Acute gastritis, carcinoma of oesophagus or large bowel, pancreatic disease, liver
                       disease
               Haemopoiesis
                    Macrocytosis (due to direct toxic effect on bone marrow or folate deficiency),
                       thrombocytopenia, leucopenia
               Bone
                    Osteoporosis, osteomalacia.
               Symptoms of alcohol dependence syndrome:
                    Rapid reinstalment of syndrome on drinking after a period of abstinence
                      The subjective awareness of a compulsion to drink
                      A narrowing of the drinking repertoire
                      Primacy of drinking over other activities
                      Increased tolerance to alcohol. Need for more alcohol to achieve same results
                      Withdrawal symptoms, ‘bad nerves’, shakiness and blackouts through to delirium
                       tremens
                     Relief from or avoidance of withdrawal symptoms by further drinking
                 Symptoms of alcohol dependence:
                     Unable to hold a drink limit
                     Difficulty avoiding getting drunk
                     Spending a considerable time drinking
                     Missing meals
                     Memory lapses, blackouts
                     Restless without drink
                     Trembling after drinking the day before
                     Morning retching and vomiting
                     Sweating excessively during the night
                     Withdrawal fits
                     Morning drinking
                     Increased tolerance
                     Hallucinations, frank delirium tremens
   Similar
 symptoms/
other disease
Investigations         Lab markings indicating alcohol misuse include elevated γ-glutamyl transpeptidase
                        and mean corpuscular volume (MCV).
                       Blood or breath tests in those who have recently been drinking.
T  Surgical
r Pharmaco              Naltrexone (opioid antagonist) can prevent relapses
e cological             Acamprosate acts on GABA, norepinephrine and serotonin receptors and can reduce
a                        drinking frequency.
t                     Are others including disulfiram and fluoxetine but seem to have limited use?
m    Non-        Patients frequency of drinking and quantity during a typical week should be established,
e Pharmaco       consumption is based on the number of units.
n   logical      Psychological treatment- informing on safe alcohol levels, recommendations where to cut
t                down if needed, simple support and advice.
                 Motivational enhancement (motivational therapy), feedback, education, agreement of
                 drinking goals.
                 Cognitive behavioral therapy
                 12 step facilitation (used by AA)

                 There is a specific treatment plan for those suffering fro delirium tremens (pg 1214)

   Disease       Self harm
Epidemiology
  Pathology
Aetiology/RF
    Signs/
  symptoms
   Similar
 symptoms/
other disease
Investigations
T    Surgical
r Pharmaco
e   cological
a      Non-
 t Pharmaco
m     logical
e
n
 t

   Disease       Somatisation Pg 1195
Epidemiology          One in ten patients presenting with a functional disorder will fulfill the criteria of a
                         chronic somatization disorder- sometimes known as Briquet’s syndrome.
  Pathology      Is probably the somatic presentation of psychological distress, although iatrogenic damage
                 (postoperatively or drugs) soon complicates issues
                      Multiple, recurrent, medically unexplained physical symptoms, usually starting in
                         early adult life.
                      Course of disorder is chronic, disabling and with long standing familial, marital and
                         occupational problems
                      Hypochondriasis- preoccupation with an assumed illness/disease e.g. AIDS/cancer.
                         Often repeatedly request laboratory tests to prove their illness or to reassure them
                         that they are well. The cycle is then repeated, with another round of worry and
                         requests. Hypochondriasis is often linked to other psychiatric disorders, particularly
                         depressive and anxiety disorders. Occasionally it is delusional, secondary to
                         schizophrenia and depressive psychosis. May occasionally exist with physical illness
                         but its severity will be disproportionate and justified.
Aetiology/RF     Aetiology unknown
                 Both mood and personality disorders are often also present
                 Often associated with dependence upon or misuse of prescribed medication, usually
                 sedatives or analgesics
                 Often a history of childhood traumas, or chronic ill health in the child or parent, which may
                 play an aetiological role.
   Signs/        Examples of physical illnesses:
 symptoms             Exhaustion
                      Dizzy spells
                      Headaches
                      Hypersensitivity to light and noise
                      Paraeasthesiae
                      Abdo/neck/ back pain
                      Nausea
                      Sexual symptoms
                      Abdo skin sensations
                 Above are the most common, but pain can be referred to anywhere and any part of the body.
                 Patient has usually multiple medical opinions and numerous negative investigations
                 Patients can ‘doctor shop’ and seem dependent doctors/ attention seeking and yet complain
                 about the care that they receive
   Similar
 symptoms/
other disease
Investigations
T    Surgical
r Pharmaco
e cological
a   Non-             Patient needs to be carefully told and reassured that their physical signs/symptoms
t Pharmaco            are due to a psychological cause.
m  logical           Further treatment consists of CEASING reassurance that no serious disease has been
e                     uncovered, since this reinforces dependence on the doctor.
n                    Doctor should carefully explore psychological and social issues if possible,
t                     demonstrating links between symptoms and stresses.
                     Repeated lab investigations should be discouraged
                     Essential that all staff and family form the same approach to the patients problems
                      as family members/staff will be split in to ‘good’ and ‘bad’ (caring and uncaring)
                      otherwise.
                     Cognitive behavior therapy can be useful.

   Disease     Delirium Pg 1218
Epidemiology        Most common psychosis seen in a general hospital
                    10-20% of elderly surgical patients have delirium during their admission.
 Pathology          Also termed ‘toxic confusional state’ and ‘acute organic reaction’
                    Impairment of attention is accompanied by abnormalities in perception and mood
                    Confusion is usually worse at night, with consequent sleep reversal so that the
                      person is asleep during the day and awake at night.
                    During the acute phase, thought and speech are incoherent memory is impaired and
                      misperceptions occur.
                    Episodic visual hallucinations and delusions occur and so the patient may be
                      restless, frightened, suspicious and uncooperative
Aetiology/RF   Predisposing factors for delirium:
                    Extremes of age (developing or deteriorating brain)
                    Any form of dementia
                    Previous head injury
                    Alcoholic brain damage
                    Previous stroke
                    Dislocation to an unfamiliar environment (e.g. hospital admission)
                    Sleep deprivation
                    Sensory extremes (overload or deprivation)
                    Immobilisation
                    Visual or hearing impairment
               Causes of delirium
                    Any infection (especially with high fever e.g. malaria, septicaemia)
                    Metabolic disturbance- Hepatic failure, Renal failure, hypoxia, disorders of
                      electrolyte balance, dehydration
                    Vitamin deficiency-Thiamin (wernike-korsakoff syndrome, beriberi), nicotinic acid
                      (pellagra), vitamin B12
                    Endocrine disease- hypothyroidism, Cushing’s syndrome
                    Intracranial causes- trauma, tumour, abscess, subarachnoid haemorrhage, epilepsy
                    Drug intoxication- Anticonvulsants, antimuscarinics, anxiolytic/hypnotics, tricyclic
                      antidepressants, dopamine agonists, digoxin
                    Drug/alcohol withdrawal
                    Postoperative states
                    Terminal illness
    Signs/          History should be taken from a witness
  symptoms          Examination may reveal the cause
   Similar
 symptoms/
other disease
Investigations
T    Surgical
r Pharmaco              Haloperidol
e   cological           Olanzapine
a      Non-        Patient should be carefully nursed and rehydrated in a quiet single room with a window that
 t Pharmaco        doesn’t allow exit.
m     logical      Drug therapy should be reviewed and stopped if possible
e                  Usually resolves within a week or two, but brain recovery usually lags behind physical
n                  recovery of the causative physical illness. Prognosis depends on the successful treatment of
 t                 the causative disease, but also the underlying state of the brain.

   Disease         Dementia Pg 1167
Epidemiology          • Affects 10% of an population over 65, and 20% over 80
                      • Commonest causes are Alzheimers disease, fronto-temporal dementia, vascular
                           dementia and dementia with Lewy bodies.
  Pathology        Progressive decline in cognitive function, usually affecting the cortex as a whole, though
                   sometimes patchily
                   Memory is especially affected, intellect gradually fails
                   Loss of emotional control, deterioration of social behavior and loss of motivation
 Aetiology/RF
      Signs/
    symptoms
     Similar
   symptoms/
other disease
Investigations
T      Surgical
r Pharmaco
e      cological
a        Non-
 t Pharmaco
m       logical
e
n
 t


    Disease        Cervical lymphadenopathy
Epidemiology
   Pathology
 Aetiology/RF
     Signs/
   symptoms
    Similar
  symptoms/
other disease
Investigations
T     Surgical
r Pharmaco
e     cological
a       Non-
 t Pharmaco
m      logical
e
n
t

   Disease       Stroke/TIA Pg 1126
Epidemiology          Stroke is the second commonest cause of death (9%) and a major cause of disability
                         worldwide
                      Approximately 2/3 of the global burden of strokes is in the middle and low income
                         countries
                      Age adjusted annual death rate from strokes is about 200 per 100000 in the UK
                         (12% of all deaths)
                      Rates are higher in Asian and black Africans than Caucasians
                      Stroke is uncommon <40 yo
                      Commoner in males
                      Death rate following a stroke is 20-25%
    Pathology         Thromboembolytic infarction (80%)
                      Cerebral and cerebellar haemorrhage (10%)
                      Subarachnoid haemorrhage (5%)
                      Arterial dissection and arteriovenous malformations also contribute
                 Definitions:
                      Stroke: a syndrome of rapid onset of cerebral deficit (usually focal) lasting >24 hours
                         or leading to death, with no cause apparent other than a vascular one.
                      Completed stroke- means the deficit has become maximal, usually within 6 hours.
                      Stroke-in-evolution: describes progression during the first 24 hours
                      Minor stroke: Patients recover without significant deficit, usually within one week.
                      Transient Ischaemic attack (TIA): Sudden focal deficit e.g. weak limb lasting from
                         seconds to 24 hours with complete recovery. This definition is unsatisfactory as after
                         one hour ischemic damage has already occurred. They have a tendency to recur and
                         may herald a thromboembolytic stroke.
                 Completed stroke caused by:
                      Arterial embolism from a distant site (usually heart, carotid, vertebral or basilar
                         arteries) and subsequent brain infarction- 70% of strokes
                      Arterial thrombosis in atheromatous carotid, vertebral or cerebral arteries with
                         subsequent infarction
                      Haemorrhage (intracranial or SAH)
                      Venous infarction
                      Carotid or vertebral artery dissection
                      Polycythemia and hyperviscosity syndromes
                      Fat and air embolism
                      Multiple sclerosis- demyelinating plaques
                      Mass lesions (e.g. brain tumour, abscesses, subdural haemorrhage)
                 Transient ischaemic attacks:
                      Usually the result of microemboli, but different mechanisms produce similar clinical
                         events
                      May be caused by a fall in cerebral perfusion (e.g. cardiac dysrhythmia, postural
                         hypotension or decreased flow through atheromatous arteries)
                      Usually averted by autoregulation (MAP of cerebral arteries is maintained between
                         60-120 mmHg due to autonomic regulation of smooth muscles in the walls of small
                         arteries.
                      25% of MRI’s show small infarcts
                      Rarely tumours and Subdural haematoma’s can produce clinically similar symptoms
                      Most common are cardiac and atheromatous plaque/ thrombi within the great
                       vessels, carotid and vertebral systems.
                   Cardiac thrombi follow AF (often secondary to valvular disease or MI)
                   Polycythemia
                   Thromboembolism from outside the brain causes 80% 0f TIA’s
               Carotid and vertebral artery dissection:
                     Dissection accounts for around 1 in 5 strokes below the age of 40 and is sometimes
                        a sequel of head or neck trauma.
                     Stroke, TIA or sudden headache/migraine like symptoms occur, sometimes with
                        neck pain at the site of dissection
Aetiology/RF       Hypertension (most treatable RF)
                   Smoking
                   Lifestyle
                   Alcohol
                   High cholesterol
                   Raised haematocrit
                   AF
                   Obesity
                   Diabetes
                   Severe carotid stenosis
                   Sleep apnoea
               Rarer risk factors:
                   Thrombocythaemia, thrombophilia
                   Low dose oestrogen containing contraceptives do not increase the risk in healthy
                       women but may with other risk factors (e.g. uncontrolled BP)
                   Drugs of abuse e.g. Cocaine
                   COX-2 inhibitors are associated with a slightly increased incidence of stroke.
               Others- see page 1127
   Signs/      TIA:
 symptoms          Sudden loss of function, usually within seconds , and lasts for minutes or hours
                       (classical definition <24 hours)
                   The site of attack shows in the signs and symptoms
                   Read about amaurosis fugax/ transient global amnesia? Pg 1128
               Cerebral infarction:
                   Clinical picture can be very different depending on the infarct site and extent.
                   Whilst the general site can be deduced from physical patterns, clinical estimations of
                       precise vascular territories are often inaccurate, when compared to imaging.
                   Following vessel occlusion brain ischaemia occurs followed by infarction, the
                       infarcted region is surrounded by a swollen which does not function but is
                       structurally intact (ischaemic penumbra). Within the ischaemic area hypoxia causes
                       neuronal damage.
                   Most common symptoms are infarction of the internal capsule following
                       thromboembolism in a middle cerebral artery branch (similar picture is created by
                       an internal carotid occlusion).
                   Limb weakness on the opposite side to the infarct develops over seconds, minutes or
                       hours (occasionally longer). Contralateral hemiplegia or hemiparesis with facial
                       weakness.
                   Aphasia is common if the dominant hemisphere is affected
                   Consciousness is usually preserved
                   After variable period, reflexes reappear, becoming exaggerated
                   Extensor plantar response occurs
               Look up brainstem infarction: Pg 1129
   Similar             Mass lesions
 symptoms/             Focal epilepsy (usually detectable by its positive features such as limb jerking)
other disease
Investigations   Clinical findings (of a TIA):
                 Diagnosis is usually made solely by its description, consciousness is usually preserved
                 May be evidence of source of embolus:
                      Carotid arterial bruit (stenosis)
                      AF
                      Valvular heart disease/ endocarditis
                      Recent MI
                      Difference between L and R brachial BP
                      Routine bloods (for ESR, polycythaemia, infection, vasculitis etc)
                      CXR
                      ECG
                      Carotid doppler studies
                 Later on:
                 MRI/CT angiographies to see if surgery is a possibility
T  Surgical           Decompressive hemicraniectomy reduces ICP and reduces mortality in middle
r                         cerebral artery infarcts- however neurological deficits remain.
e                     Internal carotid enarterectomy- usually recommended in stroke/TIA patients with
a                         internal carotid artery stenosis >70%. If successful it reduces the risk of further
t                         TIA/stroke by 75%. Has a mortality of 3% and similar risk of stroke
m                     Percutaneous transluminal angioplasty is an alternative
e Pharmaco       Prevention/ preventing reoccurrence:
n cological           Low dose aspirin
t                     Statins
                      Beta blaockers
                      ACE/CCB/ angiotensin-II antagonists
                 Acute:
                      Thrombolysis has been shown to improve outcome and should be used immediately
                          if there are no contraindications (see page 1131).
                 Afterwards botulinum/baclofen are sometimes useful in the long term to reduce severe
                 spasticity.
     Non-             Rehabilitation- Skilled physiotherapy within the first few weeks is useful for
   Pharmaco               reducing spasticity, preventing contractures and teaching patients to use walking
    logical               aids. Benefits in long term are still inadequately researched.
                      Speech therapy for those suffering from aphasia
                      Occupational therapists to alter living environments to improve peoples quality of
                          life

   Disease       Sub-arachnoid haemorrhage (SAH) Pg 1134
Epidemiology         Accounts for some 5% of strokes and has an annual incidence of 6 per 100000
                     Nearly 50% of all SAH are dead or moribund (nearly dead) before reaching hospital
                     Of those left, 10-20% re bleed and die within several weeks
  Pathology          Spontaneous arterial bleeding into the subarachnoid space, and is usually clearly
                         recognizable clinically from its dramatic onset.
Aetiology/RF     Causes:
                     Saccular (berry) aneurisms- 70%
                     Arteriovenous malformation- 10%
                     No arterial lesion found- 15%
                 Rare associations (<5%):
                     Bleeding disorders
                        Mycotic aneurisms- endocarditis
                        Acute bacterial meningitis
                        Tumours (metastatic melanoma, oligodendroglioma)
                        Arteritis
                        Spinal arteriovenous malformation causing spinal SAH
                        Coarctation of the aorta
                        Marfans, Ehlers-Danlos syndrome
                        Polycystic kidneys
   Signs/               Sudden devastating headache, often occipital
 Symptoms               Usually followed by vomiting and often by coma and death
                        Survivors may remain comatose or drowsy for hours, days, or longer
                        Less severe headaches without loss of consciousness can cause difficulty
                        SAH is any diagnosis in any sudden headache.
                        Following a major SAH there is neck stiffness and a positive Kernig’s sign
                        Papilloedema is sometimes present, with retinal and/or subhyaloid haemorrhage
                         (tracking beneath the retinal hyaloid membrane).
                      Minor bleeds cause few signs, but almost invariably headache.
   Similar       Differential diagnoses:
 symptoms/            Migraine
other disease         Acute bacterial meningitis occasionally causes very abrupt headaches
                      Cervical arterial dissection can also present with a sudden headache
Investigations        CT is the immediate investigation needed (SA or intraventricular blood is usually
                         seen)
                      Lumbar puncture (not needed if SA can be confirmed by CT but should be performed
                         if doubt remains
                      CSF becomes yellow several hours after a SAH
                      MR angiography is performed in all those potentially fit for surgery
                      In some, no aneurism or source of bleeding is found despite a definite SAH.
T  Surgical
r Pharmaco             Antihypertensive drugs
e cological            Dexamethasone can be given to reduce cerebral oedema and stabilize the blood
a                       brain barrier
t                    Nimodipine (a CCB) reduces mortality.
m    Non-        Complications:
e Pharmaco           Blood in SA space can cause obstructive hydrocephalus, seen on CT. Hydrocephalus
n   logical             can be asymptomatic but may cause deteriorating consciousness. Shunting may be
t                       necessary
                     Occasionally arterial spasm may occur after a SAH.
                 Treatment:
                     Bed rest and supportive measures

   Disease       Peripheral neuropathy Pg 1170/1172
Epidemiology
 Pathology       Definitions:
                      Neuropathy- a pathological process affecting a peripheral nerve/ nerves
                      Mononeuropathy- process affecting a single nerve
                      Mononeuritis complex- (multiple mononeuropathy and or multifocal neuropathy)
                         affects several or multiple nerves.
                      Polyneuropathy- describes diffuse, symmetrical disease. Usually commences
                         peripherally. Course may be acute, chronic, static, progressive, relapsing, or
                         recovering. Are motor, sensory, sensorimotor and autonomic. Classified broadly as
                         axonal and demyelinating types, depending on which process predominates. Many
                      systemic diseases can cause neuropathies, with loss of tendon reflexes being typical,
                      with distal weakness and distal sensory loss.
                     Reticulopathy- means disease affecting nerve roots and plexopathy, the brachial and
                      lumbosacral plexus
                     Myelopathy- means disease of the cord


               Neuropathy can occur due to variety of different mechanisms:
               Demyelination:
                     Schwann cell damage leads to myelin sheath disruption, causing marked slowing of
                        conduction e.g. Guillan- Barre syndrome
               Axonal degeneration:
                     Axon damage leads to nerve fibre dying back from the periphery. Conduction
                        velocity initially remains normal because axonal continuation is maintained in
                        surviving fibres. Axonal degeneration occurs typically in toxic neuropathies.
               Wallerian degeneration:
                     Changes following nerve section, both axon and distal myelin sheath degenerate
                        over several weeks.
               Compression:
                     Focal demyelination at the point of compression causes disruption of the myelin
                        sheath. Occurs typically in entrapment neuropathies e.g. carpal tunnel syndrome
                     Peripheral nerve compression and entrapment is recognised largely by clinical
                        features (tests include nerve conduction studies)
               Infarction:
                     Microinfarction of vasa nervorum occurs in diabetes and arteritis e.g. polyarteritis
                        nodosa. Wallerian degeneration occurs distal to the ischaemic zone
               Infiltration:
                     Inflammation of peripheral nerves by inflammatory cells occurs in leprosy and in
                        granuloma’s e.g. sarcoid and by neoplastic cells, causing neural metastasis.

               Nerve regeneration:
                   Occurs either by remyelination- recovering schwann cells spin ne myelin sheaths
                      around an axon- or by axonal growth down the nerve sheath with sprouting from
                      the axonal stump. Axonal growth takes place at 1mm per day.
Aetiology/RF
   Signs/      Peripheral nerve entrapment:
 symptoms      Carpal tunnel syndrome:
                    Median nerve entrapment at the wrist can be seen in those suffering from
                       hypothyroidism, diabetes mellitus, pregnancy (3rd trimester), obesity, rheumatoid
                       disease, acromegaly, amyloid, dialysis patients or following trauma.
                    Nocturnal tingling and pain in the hand/ forearm, followed by weakness of thenar
                       muscles.
                    Sensory loss in palm and radial 3 and a half fingers develops, followed by wasting of
                       abductor pollicis brevis (main pair of thenar eminence)
                    Tinels sign present (tapping flexor part of wrist eliciting pain and tingling), with
                       Phalens test positive (symptoms are reproduced on passive maximal wrist flexion)
               Ulnar nerve compression:
                    At cubital tunnel in the elbow, following recurrent pressure or a fracture.
                    Weakness and wasting of ulnar innervated muscles leads to clawing of the hand- the
                       hypothenar, interossei and medial two lumbricals. Sensory loss in ulnar one and a
                       half fingers (little finger and one next to it).
                    Note: deep purely motor branch of ulnar nerve can be damaged in the hand by
                       trauma e.g. crutches.
                 Radial nerve compression:
                      Compressed against the humerus (can be known as Saturday night palsy when arm
                         is draped over hard chair)
                      Wrist drop and weakness of brachioradialis and finger extension
                      Recovery is usual but variable in 1-3 months
                      Posterior interosseous nerve compression in the forearm also leads to wrist drop
                         without weakness of brachioradialis.
                 Common peroneal nerve palsy:
                      Compression of common peroneal nerve is compressed against the head of the fibula
                         causing foot drop and ankle eversion (ankle jerk preserved)
                      Patch of numbness on anterolateral border, dorsum of foot and/or lower shin
                      Usual recovery within several months.
                 POLYNEUROPATHIES:
                 Gullain-Barre syndrome (GBS):
                      Most common acute polyneuropathy, usually demyelinating but occasionally axonal
                         and probably has an autoallergic basis. Does not recur.
                      Paralysis occurs 1-3 weeks after an infection that is often trivial/ seldom identified.
                      Inducing organisms cause antibody production against peripheral nerves
                      Pt complains of weakness in distal limb muscles and/or numbness. Progress over
                         several days to 6 weeks. In 20% of cases there is weakness of respiratory and facial
                         muscles sometimes progressing to complete paralysis
                      15% are left disabled or die.
                 For other types of polyneuropathy see page 1173
   Similar
 symptoms/
other disease
Investigations         Nerve conduction studies
                       CSF protein levels for GBS/ Autoantibody tests
T  Surgical            Surgical decompression of carpal tunnel in CTS, decompression and transposition of
r                       ulnar nerve in Cubital TS
e Pharmaco             In nerve entrapments a steroid injection can give relief
a cological            Heparin for those with GBS, and immunoglobulin given IV for the first 2 weeks (after
t                       screening for IgA deficiency).
m    Non-              For nerve entrapments a splint can be applied
e Pharmaco
n   logical
t

   Disease       Epilepsy Pg 1139
Epidemiology          Is common, its prevalence is 5 times higher in developing than developed (0.5%)
                        countries and the incidence is doubled.
                      Over 2% of the population in developed countries have two or more seizures during
                        their lives, in 0.5% epilepsy is an active problem and common in primary care
                      In the UK approximately 65 people suffer a probable first seizure each day. The
                        lifetime risk of having a single seizure is 5%
                      Approximately 250000 people in the UK take anticonvulsant drugs, the mainstay of
                        treatment
  Pathology           No clear cause is found for seizures, although rarely is can be attributed to a brain
                        tumour or follows a stroke
                      Spread of electrical activity amongst neurons is usually restricted and synchronous
                        producing normal EEG’s. During a seizure, large groups of neurons are activated
                        repetitively, unrestrictedly and hypersynchronously, synaptic inhibition fails and
                        high voltage spike and wave activity results on an EEG.
                    This focal area of activity may spread to generate epileptic activity in both
                        hemispheres and thus a generalised seizure. This spread is called secondary
                        generalization
                    Focal nature of seizure may not be apparent clinically because of rapid secondary
                        generalization
                    The only other way that a generalised tonic clonic may occur is after a primary
                        generalised convulsion
                    A brain becomes epileptogenic either because neurons are predisposed to be
                        hyperexciteable, or because they acquire this tendency
                    Aura means a stereotyped perception caused by the initial focal electrical events
                        before a partial seizure, such as a smell, tingling in one limb, or strange recognisable
                        inner feelings.
                    Each person has a seizure threshold, and for some it is lower than others (e.g.
                        flashing lights)
Aetiology/RF   Cause for epilepsy is found in less than 1/3 of cases in the UK:
                    Cerebrovascular disease accounts for less than 15%,
                    Tumours for 6%
                    Alcohol related seizures for 6%
                    Post traumatic epilepsy 2%- trauma, hypoxia and surgery
                    Hippocampal sclerosis is a cause of symptomatic epilepsy (resection may be
                        possible)
                    Malformations of cortical development
                    AVM’s (arteriovenous malformations), haemotomas, brain abcesses and
                        tuberculomas
                    Neurocysticercosis
                    Genetic predisposition and developmental abnormalities (<2%)
                    Alcohol and drugs
                    Metabolic abnormalities- hypocalcaemia, hypoglycaemia, hyponatraemia, acute
                        hypoxia, uraemia, hepatocellular failre, mitochondrial disease, porphyria.
                    Provokeable seizures- photosensitivity, pyrexia
                    Sleep deprivation
                    Age (25% of new cases are in those over 65)
               For all of above in more depth look at page 1140
   Signs/      Partial seizure is epileptic activity confined to one area of the cortex with a recognizable
 symptoms      clinical pattern:
                    Simple partial seizures (without impaired awareness e.g. Jacksonian seizures)- focal
                        motor seizure, jerking usually begins on one side of the mouth or in one hand,
                        sometimes spreading to involve the entire side. This visible spread is called the
                        march of a seizure. With a frontal lesion, conjugate gaze deviates away from the
                        epileptic focus and the head turns (known as an adversive seizure). Local temporary
                        paralysis of the affected limbs sometimes follows- Todd’s paralysis.
                    Complex partial seizures (with impaired awareness)
                    Partial seizures evolving to tonic-clonic seizures
                    Apparent generalised tonic-clonic seizures, with EEG but not clinical evidence of
                        focal onset.

               Generalised seizure types:
                   Absence seizures- a) typical absences with 3 Hz spike and wave discharge (petit
                      mal)- almost inevitably starts in childhood. After the activity ceases, the patient
                      stares and pales slightly for a few seconds. The eyelids twitch, and a few muscle jerks
                      may occur. Afterwards, normal activity reoccurs. Typical absence seizures are never
                          due to acquired lesions such as tumours. Is a result of developmental abnormality
                          and children can go on to develop generalised tonic-clonic seizures in adult life.
                          b) Atypical absences with other EEG changes
                      Generalised tonic-clonic seizures (grand mal)- following vague warning, tonic phase
                          commences. Body becomes rigid for up to a minute, patient falls and often bites
                          tongue. They may be incontinent of urine or faeces. Clonic phase then begins, with
                          generalised convulsing, frothing at the mouth and bilateral, rhythmic jerking of
                          muscles. Lasts from a few seconds to minutes. Usually self limiting, followed by
                          drowsiness, confusion or coma for several hours.
                      Myoclonic seizures-Isolated muscle jerking
                      Tonic seizures-Intense stiffening of body (not followed by jerking)
                      Akinetic seizures- cessation of movement, falling and loss of consciousness
                 Classification is based on clinical pattern (above)
                      Generalised means bilateral abnormal electrical activity, with bilateral motor
                          manifestations and impaired consciousness
                      A partial (focal) seizure means that the electrical abnormality is localized to one part
                          of the brain:
                 A) Simple- without loss of awareness (e.g. one limb jerking- Jacksonian seizure)
                 B) Complex- with loss of awareness e.g. temporal lobe attack
                      Unclassifiable seizures- do not fit any of the categories above

                 Status Epilepticus- Medical emergency:
                      Continuous seizures without recovery of consciousness, consisting of prolonged
                         serial seizures (two or more) occurring with incomplete recovery of consciousness.
                         Mortality of 10-15% (over 50% have previous history of epilepsy). Not always
                         convulsive, may be absence, focal or even a continuous seizure of one part of the
                         body.
                      Has a separate management plan/ treatment plan- see page 1142

   Similar
 symptoms/
other disease
Investigations   History from a witness is crucial, and usually enables one to distinguish other causes of
                 disturbed consciousness. The onset, setting and stages of attacks are of importance.
                 Neurological examination may be normal or point to clinical diagnosis
                      Serum calcium
                      ECG
                      EEG- useful despite limitations
                      CT and/or MR imaging- indicated in all new cases (seeing whether tumour is
                        present). MR of hippocampi is used routinely to study epilepsy.
T  Surgical           Temporal lobectomy is highly effective in selective cases (amputation of the non-
r                       dominant anterior temporal lobe can be performed in those with uncontrollable
e                       seizures and hippocampal sclerosis- under 1% of epilepsy patients)
a                     Section of corpus callosum and hemispherectomy are also used.
t Pharmaco            Diazepam- IV or rectally if a seizure lasts for longer than 3 minutes or if there are
m cological             repeated seizures
e                     IV glucose (if hypoglycaemia is suspected)
n                     Antiepileptic drug levels can all be monitored and patient agreement is essential e.g.
t                       drugs include phenytoin, sodium valproate, lamotrigine, phenobarbital etc. (see pg
                        1143)
     Non-             Ensure acute patient comes to as little harm as possible, and that the airway is
   Pharmaco             maintained both during a prolonged seizure and in a postictal coma.
    logical
                     Majority are managed in primary care or as outpatients, although some with
                      frequent seizures treatment in hospital/residential care may be necessary
                     Not allowed to drive unless they have been seizure free for 12 months (commercial
                      vehicles may be stricter). If seizures are limited to sleep, patient may be permitted a
                      driving license).


   Disease     Meningitis Pg 1153
Epidemiology
 Pathology            Bacterial meningitis is fatal if left untreated, with the pia-arachnoid being conjested
                       with polymorphs. A layer of pus forms, which may organize to form adhesions
                       causing cranial nerve palsies and hydrocephalus. Cerebral oedema occurs in any
                       bacterial meningitis. Even with optimal care, acute bacterial meningitis carries a
                       mortality of 15%.
                    In chronic infection (e.g. TB) the brain is covered in a viscous grey-green exudate
                       with numerous meningeal tubercles. Adhesions are invariable.
                    In viral meningitis there is a predominantly lymphocytic inflammatory CSF reaction
                       without pus formation, polymorphs or adhesions, there is also little or no cerebral
                       oedema unless encephalitis develops.
Aetiology/RF   Microorganisms reach the meninges either by direct extension via the ears, nasopharynx,
               cranial injury, congenital meningeal defect or by bloodstream spread.
               Causes:
               Bacterial:
                    Neisseria meningitides (combined account for over 70% of cases)
                    Strep pneumonia (combined account for over 70% of cases)
                    Strep Group B
                    Staph aureus
                    Listeria monocytogenes
                    Gram negative bacilli (e.g. E coli)
                    Mycobacterium tuberculosis
                    Treponema pallidum
               Viruses
                    Enteroviruses- ECHO, coxsackie
                    Poliomyelitis
                    Mumps
                    Herpes simplex
                    HIV
                    Epstein- Barr
               Fungi:
                    Cryptoccocus neoformans
                    Candida albicans
   Signs/      Can develop over hours or minutes
 symptoms      Triad:
                    Headache
                    Neck stiffness
                    Fever
                    Acute bacterial (meningococcal infection)- pretechial or other rash, sometimes
                       sparse- medical emergency). Beware of septicaemic shock.
               Others:
                    Photophobia
                    Vomiting/nausea
                    Malaise, fever, rigors, severe headache
                         Positive Kernigs sign (flexion at both hip and knee, then extend the leg at the knee-
                          meningeal irritation if it is painful/ meets resistance)
                      Patient usually remains conscious, may be delirious if fever is high
                      Papilloedema may develop. Drowsiness, lateralising signs and cranial nerve lesions
                          indicate complications such as venous sinus thrombosis.
                      If skull fracture is present/ ear infection it is likely to be pneumococcal infection.
                      Anorexia, focal signs (diplopia, papilloedema, hemiparesis) and seizures are
                          common in chronic (e.g TB meningitis, syphilis, sarcoidosis, behcet’s)
                 In viral meninges there are less prominent meningitis signs- however bacterial may be
                 present with a deceptively mild onset

   Similar             May be difficult to differentiate between the headache of SAH, migraine and acute
 symptoms/              meningitis.
other disease          Meningitis should be considered in anyone who has headache and fever and in any
                        sudden headache
                       Chronic meningitis sometimes resembles an intracranial mass lesion, with headache,
                        epilepsy and focal signs.
                       Cerebral malaria can mimic bacterial meningitis.
Investigations         Blood cultures
                       Blood- FBC, glucose, LFT’s
                       Syphilitic serology should always be carried out
                       Lumbar puncture if signs are unclear
                       CSF stains, changes should be noted and continuous discussion with microbiologists
                        is essential.
                       If mass lesion is suspected then a CT scan must be performed because coning of the
                        cerebellar tonsils may follow
                       MRI for tuberculous meningitis- shows hydrocephalus and tuberculomas (may
                        remain normal)
                       PCR testing
T  Surgical
r Pharmaco             Immediate IV antibiotics (cefotaxime if unknown), benzylpenicillin if meningococcal
e cological             and others for other causes (pg 1155)
a                      Antibiotics should be started immediately whilst the exact microorganism
t                       responsible is identified (using CSF etc) constant discussion should take place with
m                       the microbiologists.
e                      Once Microorganism’s identified, antibiotics used should be specific and avoid
n                       resistance
t                      With pneumococcal meningitis, some evidence to support the use of dexamethasone,
                        given first with the initial antibiotics.
                       If it’s tuberculous meningitis- anti TB drugs should be given (rifampicin, isoniazid,
                        pyrazinamide) and must last for 9 months. Prednisolone should also be given for
                        three months. Mortality remains at 60% even with early treatment.
     Non-              Barrier nursing to prevent bacterial spread
   Pharmaco            Meningococcal infection needs to be reported to public health
    logical            Immunisation and prophylaxis of contacts must also take place (e.g. with rifampicin
                        or ciprofloxacin).
                       Men C is part of UK immunisation (men A sometimes given if travelling)
                       Pneumococcal vaccine is given after skull fracture
                       Hib- Haemophilus influenza is given routinely in the UK and other countries.

   Disease       Migraine and tension headache Pg 1196/1136
Epidemiology         One of the most common symptoms seen in medical practice
                     Over 20% of any population worldwide report migrainous symptoms- in 90% of
                      these symptoms started before 40 years of age.
 Pathology         Pain receptors are located at the base of the brain in arteries and veins and
                      throughout meninges, extracranial vessels, scalp, neck and facial muscles, paranasal
                      sinuses, eyes and teeth- brain substance is almost devoid of pain receptors.
                   Pain is mediated by both mechanical and chemical receptors (e.g. stretching of
                      meninges, histamine stimulation etc).
               Recap of the types of headache:
                   Chronic (benign) and recurrent headaches- last for hours/days and are band-like
                      generalised pains with a history of several years or months are often muscle
                      tension/ migraines- depression is a common accompaniment. Localized pain of short
                      duration (minutes to hours)- sinusitis, glaucoma and migrainous neuralgia should be
                      considered.
                   Pressure headaches- IC mass lesions- stretch meninges and basal vessels, increasing
                      CSF pressure, cerebral oedema- these all typically become worse when lying down.
                      Any headache present on waking and made worse by coughing, straining, sneezing
                      may be due to a mass lesion. Vomiting often accompanies pressure headaches.
                   Headaches with scalp tenderness- in those over 50 suspect giant cell arteritis
                   Headaches of subacute onset- any headaches that have developed of days or weeks
                      with/without features of pressure headaches should always raise suspicion of IC
                      mass or disease. Encephalitis, viral meningitis, chronic meningitis should be
                      considered.
                   Headache following trauma- majority lasting days weeks or months are usually
                      benign- but beware of subdural haematoma.
                   Single episode of severe headache- SAH/ Cervical artery dissection- very sudden
                      onset, Migraine, Meningitis (occasionally)- with neck stiffness, vomiting, rash
                   Cluster headaches fall under facial pain (pg 1138)
               Tension headaches:
                   Vast majority of chronic daily headaches/ recurrent headaches are thought to be
                      caused by neurovascular irritation and referred to scalp muscles and soft tissues,
                      although the exact pathogenesis remains unclear.
                   Migraines are recurrent headaches associated with visual and GI disturbance
                      (borderland between tension headaches and migraines may be indistinct)
               Migraines:
                   Changes in brainstem blood flow have been seen on PET scanning leading to
                      unstable trigeminal nerve nucleus and nuclei in the basal thalamus- results in the
                      release of calcitonin related peptide, substance P and other vasoactive peptides
                      causing neurogenic inflammation. Causes pain and vasodilation of cerebral and dural
                      vessels which contribute towards the headache.
Aetiology/RF   Migraines:
                   Genetic factors may play some part
                   Weekend migraine (relaxation)
                   Some food triggers- chocolate (high in phenylethylamine), cheese (high in tyramine)
                   Noise and irritating lights
                   Association with premenstrual symptoms
                   Puberty/ menopause
                   Pregnancy/ initial hpt
   Signs/      Tension headaches:
 symptoms          Tight band sensations
                   Pressure behind the eyes
                   Throbbing/bursting sensations
                   May be precipitating factors such as: worry, noise, concentrated visual effort, fumes.
                     Depression is also a frequent co-morbid feature
                     Analgesic overuse is a prominent cause of headache.
                 Migraines:
                     Prodromal symptoms are usually visual and related to depression if visual cortical
                        function or retinal function- can last a few minutes to an hour.
                     Unilateral patchy scotoma (retina), hemianopic symptoms (cortex), teichopsia
                        (flashes) and fortification spectra (jagged lines like battlements) are common
                     Transient aphasia may occur- with tingling, numbness, weakness on one side and
                        nausea.
                     Headache follows- usually hemicranial (splitting of the head), nausea increases and
                        vomiting occurs
                     Patient is irritable and prefers the dark. After several hours (and perhaps diuresis)
                        migraine settles and sleep often ensues.
                     Common migraine usually has vague prodromal symptoms
                     Basilar migraines include circumoral and tongue tingling, vertigo, diplopia, transient
                        visual distubancre (even blindness), syncope, dysarthria and ataxia
                     Hemiparetic migraine- classical migraine but one sided i.e. resembling a stroke but
                        with recovery within 24hours.
                     Opthalmoplegic and facioplegic migraine- 3rd, 4th or 7th nerve palsy with s migraine.
                        Rare.
                     Are other even rarer types- see page 1139.
   Similar           Other types of headache/ other cause – see pathology.
 symptoms/           SAH
other disease        Meningitis
                     Thromboembolytic TIA’s (maximum deficit is present immediately and headache is
                        unusual)
                     Unilateral tingling may be sensory epilepsy- usually progresses though.
Investigations       If IC pathology is suspected- head CT/MRI.
                     Meningitis?- lumbar puncture/ blood cultures etc
                     Bloods
T  Surgical          Surgical removal of tumours/ resection of lesions etc
r Pharmaco           Antidepressants for those that are depressed
e cological          Drugs for recurrent migraine- paracetamol/ other analgesics, triptans
a                    Antiemetics- metoclopramide
t                    Prophylaxis- pizotifen, propanalol, amitriptyline.
m    Non-            Explanation/ reassurance (imaging is often needed)
e Pharmaco           Avoidance of evident causes (e.g. bright light)
n   logical          Analgesic withdrawal
t
                     Physical treatment- massage, ice packs, relaxation
                     Avoidance of dietary factors- migraine
                     Change of oral contraceptives

   Disease       Parkinson’s disease/ parkinsonism Pg 1145/ 1148
Epidemiology          Common worldwide condition that has a prevalence of 150/100000 increasing
                        sharply
  Pathology      Idiopathic parkinsons:
                      Few clues about causes of idiopathic Parkinson’s disease, relatively uniform
                        worldwide spread suggests it is unlikely that an environmental agent is responsible.
                      Nicotine decreases risk
                      MPTP (byproduct of illicit stimulant drug production) causes severe parkinsonism
                      Encephalitis lethagia-survivors sometimes go on to develop parkinsonism
                      Genetic factors- is not usually familial, but can be clustering in early onset in some
                       families and some mutations on genes have been noted (Pg 1146)
                    The pars compacta of the substantia nigra undergoes progressive neuronal
                       degeneration. Eosinophilic inclusion bodies (lewy bodies) develop. These contain
                       protein filaments. Degeneration also occurs in other basal ganglia nuclei. Loss of
                       dopamine (and melanin) in the striatum, correlating with cell loss and the degree of
                       akinesia.
                Drug induced parkinsonism:
                    Phenothiazines and butyrophenones (also reserpine and methyldopa used to treat
                       hpt) induce Parkinsonism, usually with little tremor.
                    Tricyclic antidepressants also produce some slowing
                    Tend not to progress and settle when drugs are stopped.
Aetiology/RF
   Signs/              Tremor (4-7Hz pill-rolling at rest, typical decreases with action) and…
 symptoms              Rigidity- stiffness develops throughout movements and is equal in opposing muscle
                        groups, in contrast to the selective increase in limb tone found in spasticity. This
                        ‘plastic rigidity’ is usually more marked on one side and present in the neck and axial
                        muscles. Can be felt best when a joint is moved slowly and gently; tone increases
                        when the opposite arm moves actively. When stiffness occurs with a tremor, smooth
                        lead pipe rigidity is broken up into jerky resistance to passive movement-
                        cogwheeling. And…
                    Akinesia-slowing of movement (bradykinesia) is an additional handicap, distinct
                        from rigidity. Difficulty initiating movement, rapid fine finger movements. Facial
                        immobility leads to blank expression and snakelike stare…these develop slowly over
                        months or several years- together with changes in posture (stooping is common, gait
                        becomes festinant and simian and shuffling takes place with poor arm swinging,
                        balance deteriorates but gait remains narrow leading to falls later in illness).
                    Common initial symptoms are a tremor and slowness
                    Limbs and joints feel stiff; they ache
                    Fine movements become difficult
                    Slowness causes difficulty getting into or out of bed
                    Writing becomes small/spidery tending to tail off
                    Relatives often notice the impassive face
                    Almost always more prominent on one side
                    Speech becomes monotone and eventually becomes slurring dysarthria- may be lost.
                    Depression common
                    GI and others- constipation, heartburn, dribbling dysphagia, weight loss, skin greasy
                        and sweating, urinary difficulties.
                Drug induced parkinsonism can also have other symptoms from Phenothiazines and
                butyrophenones):
                    Akathisia- restless, repetitive and irresistible need to move
                    Acute dystonic reactions- sustained upward gaze, spasmodic torticollis etc. occur
                        rapidly and suddenly, offending drug should be avoided forever.
                    Chronic tardive dyskinesia’s- mouthing and lick smacking grimaces
                Parkinsonism plus:
                    When Parkinsonism occurs with other features and specific pathology (progressive
                        supranuclear palsy is commonest).
                Post- encephalitic parkinsonism and akinetic- rigid syndromes in children (Wilsons disease/
                Athetoid cerebral palsy) also exist.
   Similar
 symptoms/
other disease
Investigations   No lab test- diagnosis is made by the recognition of signs and symptoms for idiopathic.
T    Surgical         Stereotactic lesions (often in venterolateral nucleaus of thalamus or in globus
r                        pallidus) were widely used before levodopa
e                     Thalamic stimulation is used increasingly, sometimes with dramatic improvement.
a                     Tissue implantation/ stem cells have not yet produced reliable results.
 t Pharmaco           Levodopa and/or dopamine agonists produce a striking initial improvement
m cological              (avoided until necessary due to side effects). For more info see page 1147.
e                     Antioxidants such as vitamins C and E may act as neuroprotective agents
n                     Antidepressants (SSRI’s work best as tricyclics have extrapyramidial side effects)
 t     Non-           Physiotherapy
   Pharmaco           Physical aids
    logical

   Disease       Urinary tract Infection Pg 599 and Pyelonephritis
Epidemiology          Far more common in women
                      Incidence is 50000 per million persons per year and accounts for 1-2% of patients in
                         primary care
                      Recurrent infection causes considerable morbidity- if complicated it can cause
                         severe renal disease including end-stage renal failure, it is also a common source of
                         life-threatening gram-negative septicaemia
  Pathology           Infection is usually due to bacteria from the patients own flora, spreads usually via
                         the transurethral route but can spread in the bloodstream, lymphatic’s or direct
                         extension
                      Symptoms are related to virulence of bacteria, however the inflammation and injury
                         are determined by the host response not the bacterium.
                 Virulence:
                      Ability to adhere to epithelial cells determines the degree of virulence of the
                         organism. This depends on flagellae, aorobactin, haemolysin and adhesins on the
                         bacterial fimbrae
                      Two types of E.coli, those with type 1 fimbrae (FimH) associated with cystitis and
                         those with type P fimbrae (PapG) commonly responsible for pyelonephritis
                 Complicated versus uncomplicated infection:
                      Important to distinguish between those with functionally normal urinary tracts and
                         those with abnormal tracts.
                      In functionally normal tracts, persistent/ recurrent infection seldom results in
                         serious kidney damage (uncomplicated UTI).
                      In those with abnormal urinary tracts- with stones, or associated diseases such as
                         diabetes mellitus (causes kidney damage by itself) may be made worse by infection
                         (complicated UTI). Especially with proteus- combination of infection and obstruction
                         results in severe, sometimes rapid kidney damage (obstructive pyonephrosis) and is
                         a major cause of gram-negative septicaemia.
                 Acute pyelonephritis:
                      Small renal cortical abscesses and streaks of pus in the renal medulla are often
                         present. Histologically there is infiltration by polymorphonuclear leucocytes and
                         polymorphs in the tubular lamina.
                 Reflux nephropathy (sometimes called chronic pyelonephritis), combination of:
                      Vesicoureteric reflux and
                      Infection acquired in infancy or early childhood
                      The vesicoureteric junction usually acts as a one-way valve, however in this instance,
                         when the bladder contracts urine is forced back up the ureter. Also leads to
                         incomplete bladder emptying (as urine falls back down ureters) and so predisposes
                         to infection. Refluxed infected urine causes kidney damage.
                       Reflux usually ceases at puberty (bladder base grows), damage already done goes on
                        to progressive renal fibrosis
                      Predisposes to hpt/ end stage renal failure in later life
                 Relapse or reinfection?
                      Relapse- recurrence of bacteruria of same organism within 7 days of completing
                        antibiotics- failure to eradicate organisms, usually due to stones, scarred kidneys,
                        polycystic disease or bacterial prostatitis
                      Reinfection- bacteria absent for at least 14 days after treatment followed by
                        recurrence of same/ different organism
Aetiology/RF          Females
                      Previous antibiotic use?
   Signs/             Frequency of micturition by day and night
 symptoms             Painful voiding (dysuria)
                      Suprapubic pain and tenderness
                      Haematuria
                      Smelly urine
                      Can present with minimal/ no symptoms
                      Possibly abdo pain, haematuria
                 Above symptoms relate to bladder and urethral inflammation commonly called cystitis and
                 suggest lower tract infection
                      Loin pain and tenderness
                      Fever and systemic upset
                 Above suggest infection to the pelvis and kidney known as pyelonephritis/ pyelitis
   Similar            Urethral syndrome- pg 602
 symptoms/
other disease
Investigations         Mid steam urine sample- checking for pyuria/ culture
                       CT scanning for pyelonephritis can show wedge shaped areas of inflammation in the
                        renal cortex.
                       CT for reflux nephropathy- irregular renal outlines, clubbed calyces and reduction in
                        renal size
                       Urograms
                       USS for those with suspected pyelonephritis that may need drainage also could be
                        used to check bladder emptying.
                       MRI occasionally
T  Surgical            Drainage of obstructed pyonephrosis (stones) by percutaneous nephrostomy
r Pharmaco             Antibiotics- e.g. trimethoprim, amoxicillin. If resistant- co-amixclav/ciprofloxacin.
e cological             Can be given IV if patient has acute pyelonephritis
a    Non-              High fluid intake (atleast 2L)
t Pharmaco             Test pregnant women as they may have an asymptomatic bacteraemia, which is far
m   logical             more likely to cause acute pyelonephritis.
e                      For UTI’s with catheters, the catheter needs removing and replacing before any
n                       antibiotic treatment is started
t                      Bacterial prostatitis, carbuncles and TB see PG 603

   Disease       Hydronephrosis Pg 614
Epidemiology         Equal incidence between males and females, however in the elderly it is more
                       common in males due to BPH
  Pathology          Dilation of the renal pelvis, often caused by obstruction.
                     Progressive rise in intraluminal pressure causes dilation proximal to the site of
                       obstruction, leading to compression and thinning of the renal parenchyma,
                       eventually reducing it to a thin rim and resulting in a decrease in the size of the
                       kidney.
                    Acute obstruction causes ischemic interstitial damage and compression of the renal
                       substance.
Aetiology/RF   Aetiology:
                    Obstructing lesions may lie within the lumen, in the wall of the urinary tract, or
                       outside the wall.
               Causes:
               Within lumen:
                    Calculus
                    Blood clot
                    Sloughed papilla (diabetes, analgesia abuse, sickle cell)
                    Tumour of renal pelvis or ureter
                    Bladder tumour
               Within the wall:
                    Pelviureteric neuromuscular dysfunction (congenital 10% bilateral)
                    Ureteric stricture (TB)
                    Congenital magaureter
                    Congenital bladder neck obstruction
                    Neuropathic bladder
                    Urethral stricture
                    Congenital urethral valve
                    Pin-hole meatus
               Pressure from outside:
                    Pelviureteric compression
                    Tumours
                    Diverticulitis
                    AA
                    Retroperitoneal fibrosis
                    Accidental ligation of ureter
                    Retrocaval ureter
                    Prostatic obstruction
                    phimosis
   Signs/      Of upper tract obstruction:
 symptoms           Loin pain (can be dull or sharp, constant or intermittent). Exacerbated by measures
                       that increase urine volume (and hence distension)
                    Anurea is strongly suggestive of complete bilateral obstruction
                    Polyuria may occur in partial obstruction owing to an impairment in renal tubular
                       concentrating capacity
                    Intermittent anueria and polyuria suggests intermittent complete obstruction
                    Infection complicating obstruction may give rise to malaise, fever and septicaemia
               Of bladder outflow obstruction:
                    Symptoms may be minimal
                    Hesitancy, narrowing and diminished stream, terminal dribbling and sensation of
                       incomplete bladder emptying
                    Frequent passing of small amounts of urine (if large volume of residual urine
                       remains). Can be known as ‘overflow incontinence’ or ‘retention with overflow’
                    Infection often occurs, causing increased frequency, urgency, urge incontinence,
                       dysuria and the passage of cloudy smelly urine.
               Signs:
                    Loin tenderness
                    Enlarged hydonephrotic tissue is often palpable
                    May be percussed/ felt
                       Examination of external genitalia, rectum and vagina is crucial, since prostatic
                        obstruction and pelvic malignancy are common causes of urinary tract obstruction
   Similar
 symptoms/
other disease
Investigations         Routine bloods and biochemical investigations- raised serum, creatinine,
                        hyperkalaemia, anaemia of chronic disease or blood in urine
                       Plain abdo X- ray- may detect radiolucent stones/ calcification. Can miss bones lying
                        over skin.
                       Helical (spiral) CT scanning- has high sensitivity and can visualize uric acid stones
                        (radiotranslucent) as small as 1mm as well as details of the obstruction.
                       Ultrasonography- Rules out upper urinary tract dilation. False positives can be seen
                       Excretion Urography
                       Radionucleotide studies
                       Antegrade pyelography and uretography
                       Retrograde uretography
                       Cystoscopy, urthroscopy and urthography
T  Surgical            Nephrostomy- allows temporary drainage of urine
r                      Extracorporeal shock wave lithotripsy/ surgery to remove calculi/ ureteroscopy
e                       with a tag laser
a Pharmaco             Analgesics as it can be VERY painful.
t cological            Antibiotics if infection is present
m    Non-              Dialysis may be needed in some patients prior to surgery
e Pharmaco             Attempt to treat underlying condition
n   logical            Prevent and treat infection
t

   Disease       Acute renal failure (ARF)/ Acute renal injury (ARI) Pg 619
Epidemiology         Incidence of hospital acquired AKI has increased, and community acquired AKI on
                        admission to hospital is about 1% in the UK- 50% of which are imposed on chronic
                        renal disease.
                     Incidence of severe AKI is about 130-140/million/year and mild is 200/million/year
                     Sepsis in the presence of AKI has significantly worse prognosis than AKI on its own.
                     Can have mortality rates of 50-70%.
  Pathology          ARF= failure of renal excretory function due to depression of the GFR, accompanied
                        by the failure of EPO production, vitamin D hydroxylation, regulation of acid base
                        balance and regulation of salt and water balance and blood pressure.
                     Defined as an abrupt deterioration in parenchymal renal function, which is usually
                        (but not invariably) reversible over a period of days or weeks.
                     Difficult to assess between chronic and acute renal failure use RIFLE- risk, injury,
                        failure, loss, end-stage renal disease. RIF= renal dysfunction LE= outcome measures.
                     Renal failure results in reduced excretion of nitrogenous waste products, of which
                        urea is the most commonly measured
                     Raised serum concentration (uraemia) is classified as a) prerenal, b) renal, C)
                        postrenal. More than one category may be present in an individual patient
                 Prerenal uraemia:
                     Impaired perfusion of the kidneys with blood, as a result of hypovolaemia,
                        hypotension, impaired cardiac pump efficiency, or vascular disease limiting renal
                        blood flow. Could be a combination of the above.
                     Usually kidney is able to maintain GFR close to normal despite wide variations in
                        renal perfusion pressure and volume status- ‘autoregulation’.
                     Further drop in renal perfusion leads to a drop in GF and causes prerenal uraemia,
                         which can cause parenchymal kidney damage and the development of acute renal
                         failure.
                      Excretory function in prerenal uraemia improves once normal renal perfusion has
                         been restored
                      Can be caused by ACE inhibitors/ NSAIDS
                 Postrenal Uraemia:
                      Obstruction of the urinary tract at any point from the calyses to the external urethral
                         orifice (calculi, pelviureteric junction obstruction, obstructive megaureter,
                         retroperitoneal fibrosis, BPH etc)
Aetiology/RF     Prerenal:
                      NSAIDS/ ACE inhibitors
                 Postrenal- Any that predispose you to renal tract obstruction:
                      Hypercalcaemia, hyperparathyroidism, renal tubular acidosis
                      TB
                      See pg 614
                 Renal:
                      Due to acute renal tubular necrosis, disease affecting the intrarenal arteries and
                         arterioles as well as the glomerular capillaries e.g. vasculitis.
                      Others: Hpt, cholesterol embolism, haemolytic uraemic syndrome,
                         thrombocytopenic purpura, pre-eclampsia and crescentic glomerulonephritis,
                      Acute tubular necrosis- renal ischaemia, renal toxins, drugs, cholestatic jaundice etc
    Signs/            Oliguria
  symptoms            Uraemia
   Similar       Can be many other causes of altered serum urea:
 symptoms/            Low protein intake, liver failure, sodium valproate treatment- low
other disease         Corticosteroid treatment, tetracycline treatment, gastrointestinal bleeding- high
                 Creatinine:
                      Low muscle mass- low
                      High muscle mass, red meat ingestion, muscle damage (rhabdomyolysis), decreased
                         tubular excretion (e.g. cimetidine)- high
Investigations   To determine between pre-renal and postrenal failure:
                      Urine specific gravity and urine osmolarity
                      Urine sodium
                      Fractional excretion of sodium
                      However above are no real match to clinical assessment.
T  Surgical
r Pharmaco              IV fluids if prerenal failure is due to hypovolaemia/ hypotension (however be careful
e cological              not to overload them as prerenal and renal uremia may coexist leading to them
a                        becoming overloaded.
t    Non-        With renal tubular necrosis, idea is to keep the patient alive until spontaneous recovery of
m Pharmaco       renal function occurs
e   logical      Fluid measurements/ balancing
n                Good nursing and physiotherapy
t                Treat any emergency measures such as hyperkalaemia, pulmonary oedema, sepsis, drugs,
                 fluid and electrolyte imbalance, need for dialysis, continual renal replacement treatment.

   Disease       Benign prostatic hypertrophy Pg 645
Epidemiology         Occurs most often in men over the age of 60
                     Much less common in Asians, unheard of in eunuchs
  Pathology          Hyperplasia affects the glandular and CT elements of the prostate.
                     Enlargement of the gland stretches and distorts the urethra, obstructing bladder
                        outflow
Aetiology/RF
   Signs/              Frequency of urination
 symptoms              Nocturia
                       Difficulty/ delay in starting urination
                       Variability and reduced stream and pot-void dribbling
                       Acute retention or overflow incontinence may be present
                       Occasionally, severe haematuria results from rupture of prostatic veins/ result of
                        bacteruria/ stone disease.
                     Occasionally present with severe renal failure
                 Abdo examination for bladder enlargement is essential and rectal examination is essential-
                 BPH feels smooth
   Similar
 symptoms/
other disease
Investigations         PR
                       PSA levels in blood
                 If prostatic carcinoma is suspected:
                       Transrectal USS/ultrasonography of prostate
                       Prostatic biopsy
                       Endo rectal coil MRI detects any extraprostatic extension
                       Look for bone lesions on x-ray.
T  Surgical            Used if medical treatment fails or if there is deterioration in renal function/ upper
r                        tract dilation. Results in prostatectomy
e Pharmaco             Alpha blockers- tamulosin are used as they relax the smooth muscle within the
a cological              prostate
t                      Finasteride is also used- blocks production of dihydrotestosterone- the androgen
m                        primarily responsible for prostate growth.
e                      Analgesics
n    Non-              Mild-moderate symptoms should be managed by ‘watchful waiting’ as treatment can
t Pharmaco               make it worse.
    logical            In acute retention- relieve pain and drain urine by urethral catheter insertion (if
                         impossible, then suprapubic should be carried out)
                       Catheter may remain in.

   Disease       Prostate carcinoma Pg 491/ 646
Epidemiology         Accounts for 7% of all cancers in men and is the sixth most common cancer
                        worldwide
                     Malignant change becomes increasingly common with age
                     By the age of 80 years, 80% of men have malignant foci within the gland, but most of
                        these appear to lie dormant.
                     Histologically the tumour is an adenocarcinoma
                     75% of men over the age of 80 die have prostate ca- but not because of there
                        prostate cancer.
 Pathology
Aetiology/RF           Hormonal factors are thought to play a role
   Signs/              Usually with symptoms of lower urinary tract obstruction
 symptoms              Less common are symptoms of metastatic spread (e.g. back pain, weight loss,
                        anaemia)
                       Can also be discovered by the finding of a hard irregular gland on rectal examination
                       Can be discovered as unexpected histological result after prostatectomy for BPH
                       Screening for PSA also can present new cases
                       Treatment of well people carries morbidity of urinary incontinence and sexual
                        dysfunction with no evidence of increased survival.
   Similar
 symptoms/
other disease
Investigations         Serum PSA
                       Transrectal USS/ultrasonography of prostate
                       Prostatic biopsy- histologically graded using gleason score
                       Endo rectal coil MRI detects any extraprostatic extension
                       Look for bone lesions on x-ray.
T  Surgical            Localised disease- radical prostatectomy
r                      Radical disease can be managed by orchidectomy (many men refuse)
e Pharmaco             Prophylatic finasteride therapy can prevent or delay the appearance of prostatic
a cological             carcinoma in men above the age of 55 years, but usually at the expense of sexual side
t                       effects and increased risk of high grade cancer
m                      Can use Luteinising hormone-releasing hormone analogues such as buserelin or
e                       goserelin before and after radiotherapy.
n                      Can also use Abiraterone.
t                      Monthly depot injections
                       Bisphosphonates can reduce bony pain in mets
                       Analgesics
     Non-              If the cancer is confined to the gland- radical prostatectomy or radiotherapy is the
   Pharmaco             choice of treatment (external beam radiotherapy or brachytherapy implants)
    logical            If it is advanced- palliative care may be the only option


   Disease       Asthma Pg 856/ 846
Epidemiology         10%-15% of people in their second decade of life develop asthma. More common in
                        developed countries like New Zealand, Australia and the UK and is far rarer in Far
                        eastern countries such as China, Malaysia, Africa and central and Eastern Europe.
  Pathology          Extrinsic: this implies that a definitive external cause can be identified. This form of
                        asthma is most frequent in atopic-individuals who show positive skin-prick reaction
                        to common inhaled allergens. 90% of children and 50% of adults who have asthma.
                        An over looked cause of late-onset asthma in adults is sensitization to chemicals or
                        biological products in the workplace.
                     Intrinsic or cryptogenic: when no causative agent can be identified to be causing the
                        asthma. This type of asthma usually starts in the middle ages (late onset).
                        Nevertheless to say many patients with adult – onset asthma show positive skin
                        tests and on close questioning give a history of respiratory symptoms compatible
                        with child hood asthma.
                 Causes and triggers of asthma:
                     Drugs (oral and/or topical) e.g. NSAIDS, β-adrenoreceptors blocking agents,
                        Atmospheric pollution e.g. sulphur dioxide, ozone, particular matter, occupational
                        sensitizers e.g. isocyanates, colophony fumes, Environmental exposure to allergens e.g.
                        Dermatophagoides pteronyssinus, grass pollen, domestic pets, Viral infections e.g.
                        Rhinovirus, Parainfluenza virus, RSV, Cold air, emotion, irritation dusts, vapours and
                        fumes e.g. perfume, cigarette smoke.
                     Atopy and allergy: one of the reasons for someone suffering from an asthma attacks
                        is their body is hyperresponsive. This is due to an increase in circulating IgE, which
                        is an antibody which reacts to common materials present in the environment. There
                        is a genetic factor which can be associated with the hyper responsiveness of the
                        people suffering from asthma, one specific gene is a gene which is found on
                        chromosome 2 called PHF11. This gene controls IgE synthesis. Also there has been a
                        link between different environments which children are brought up in and what
                        they are exposed to. The Hygiene hypothesis.
                     Increased responsiveness of the airways of the lung (airway hyperresponsiveness):
                        this is when asthma is brought about by: extreme exertion, wheezing or prolonged
                        periods of coughing following a viral infection, cough variant asthma, seasonal
                        wheeze in pollen season, allergic rhinitis. The reasons this cause problems with
                        breathing is that the airways become inflamed due to inflammation, and persistent
                        attacks will cause tissue remodelling.
                 Pathogenesis:
                     Inflammation: Mast cells are increased in both the epithelium and surface secretions
                        of asthmatics. Is involved in bringing about the immediate asthmatic reaction (via
                        histamine release, prostaglandins D2 (PGD2) and leukotriene C4 (LTC4)). Eosinophils
                        found in large numbers in the bronchial walls and secretions of asthmatics. They are
                        attracted to the region by the presence of eosinophilopoietic cytokines (IL-3, IL-5
                        and GM-CSF) and chemokines. These also enhance the mediators secretions (LTC4,
                        MBP, ECP, EPX) and these are toxic to the epithelial cells. These can be decreased by
                        corticosteroids. Macrophages (dendritic cells) and lymphocytes. They are
                        present in abundance in the mucous membrane of the airways and the alveoli. The
                        dendritic cell have a role it the initial uptake and presentation of allergens to
                        lymphocytes. The can release prostaglandins, thromboxane, LTC4 and LTB4 and
                        platelet-activating factor (PAF). These can activities can be influenced by
                        corticosteroids but not β2-adrenoceptor agonists.
Aetiology/RF         Family history,
                     High Serum antibodies (IgE)
                     Occupational sensitizers
                     Cold air and exercise
                     Atmospheric pollution and irritant dusts, vapours and fumes
                     Emotional
                     Drugs

   Signs/              Cough,wheeze, SOB
 symptoms              Worse in evenings/ at night
                       Cough can sometimes predominate- children coughing at night
                       May be frequent or infrequent
                       Some have chronic symptoms upon which there are fluctuations
   Similar          -
 symptoms/
other disease
Investigations         Bronchial provocation test: is when a individual is asked to inhale increasing
                        concentrations of either histamine or methacholine. This test induces transient
                        airflow limitation is susceptible individuals (approx 20% of pop). The dose of
                        agonist necessary to produce a 20% fall in FEV1 is know as the PD20 FEV1. Patients
                        with clinical symptoms of asthma respond to very low doses of methacholine PD20
                        FEV1 (<11        ). In general the greater the degree if hyperreactivity the more
                        persistent the symptoms.
                       Respiratory function test: used to measure the peak expiratory flow (PEF) on
                        walking, prior to a taking a bronchodilator and before bed after taking a
                        bronchodilator. These specific are used to demonstrate the variable airflow
                        limitations which characterise the disease. This is also used to measure the patient
                        asthma activity; good for assess long-term response to treatment and to monitor the
                        asthma.
                       Exercise test: this has been widely used in the diagnosis of asthma in children. The
                        subject should run for 6 min on a treadmill at a workload sufficient enough to get
                      heart rate about 160 beats per min. Neg test doesn’t rule out asthma.
                     Trial of corticosteroids: all patients who present with serve airflow limitation should
                      undergo a formal trial of corticosteroids (30mg/daily for 2 weeks) substantial
                      improvement (FEV1 >15%) confirms presence of reversible elements and shows
                      corticosteroids will benefit patient.
                     Blood and sputum tests: patients with asthma can have increased number of
                      eosinophils present in the blood (>0.4× 109/L). The presence a large number better
                      diagnostic tool.
                     Skin tests: skin prick test should be done in all cases of asthma to see what allergen is
                      causing the asthma.
                     Allergen provocation test: should be done in cases of suspected occupational asthma.
T  Surgical    N/A
r Pharmaco     National and international guidelines have been made to deal with treatment of asthma and
e cological    they involve these three things: -asthma self-management (Peak flow meters) and discuss
a              plan with patient and write it down, -Appreciate asthma is an inflammatory disease so start on
t              therapy even in the mild cases. –use of short-acting bronchodilators. And increase where
m              necessary as disease progress.
e              Example of drugs B2 –adrenergic agonists (salbutamol (100µg) or terbutaline (250µg)),
n              Antimuscarinic bronchodilators (ipratropium bromide (20-40µg TDS/QDS) or oxitropium
t              bromide (200µg twice a day)), Anti-inflammatory drugs (sodium cromoglicate or
               nedocromil sodium, dose depends on device), inhaled corticosteroids (beclometasone
               dipropionate (50,100,200 and 250 µg), oral corticosteroids (should only be started if patient
               not controlled on inhaled version. Dose should be kept as low as possible 30mg daily
               prednisolone)
     Non-      Aims of treatment is to: abolish symptoms, restore normal or best possible lung function,
   Pharmaco    reduce risk of severe attacks, enable normal growth to occur in children, minimize absence
    logical    from school or employment. This involves: patient and family education, patient and family
               participation in treatment, avoidance of identified causes as best as possible, use of lowest
               effective doses of convenient medications to minimise short-term and long-term side effects.
               So Control of extrinsic factors need to be achieve e.g. by avoidance of environmental
               causes, avoidance of medications

   Disease     Chronic obstructive pulmonary disease (COPD) Pg 835
Epidemiology       The global initiative in obstructive lung disease (GOLD) predicts that COPD will
                      become the third most common cause of death worldwide and the fifth most
                      common cause of disability world-wide by 2020.
                  • Predicted to become 3rd most common cause of death by 2020.
                  • Levels of COPD lower in females than males (both declining)
                  • Socio-economic cost- 7% of all the days off work due to sickness are due to COPD.
                  • Hospital admissions falling slowly over past 25 years

 Pathology     The most consistent pathological finding in patients who have or died of COPD are
               hypertrophy and increased number if mucus-secreting goblet cells of the bronchial tree. The
               airways which are firstly affected are the small airways where you get squamous cell
               metaplasia. The early part of the narrowing of the small airway is reversible. Along with the
               squamous cell metaplasia you get scarring both of these causing narrowing of the small
               airway. The disease then progress and the squamous cell metaplasia spreads to the large
               airways. Results in the symptoms of COPD. If accompanied by emphysema the airway
               limitation is even more severe. When the disease gets worse the people suffering from COPD
               depend on the hypoxaemia drive to drive their ventilation. As the they lose their
               hypercapnic drive. REMEMBER COPD PATIENTs RUN WITH A LOWER LEVEL OF PO2 - THIS
               DRIVES THEIR VENTILATION. ATTEMPTS TO ABOLISH THE HYPOXAEMIA CAN MAKE THE
               SITUATION WORSE.
Aetiology/RF        •   In developed countries, cigarette smoking accounts for over 90% of cases.
                    •   Despite this, only 10-20% of heavy smokers develop COPD.
                    •   Climate and air pollution- smaller role in development however risk increases
                        during heavy atmospheric pollution.
                    •   Urbanisation and social class are difficult to separate from smoking as risk factors.
                    •   Diet has not been proven to be risk factor.
                    •   Infections are dealt with badly- leading to ‘exacerbations’ (unsure if this leads to
                        increased progression of airflow obstruction).
                    •   α1-Antitrypsin deficiency. α1- Antitrypsin is a protease inhibitor that inhibits
                        enzymes able to destroy alveolar wall CT.

   Signs/              Cough with the production of sputum, wheeze and breathless all following years of
 symptoms               smoking.
                       Infections normally cause the symptoms to become worse giving purulent
                        symptoms.
                       Cold, foggy weather and atmospheric pollution seems to worsen the symptoms. In
                        advance disease mild exercise will cause breathlessness.
                 Signs:
                 Mild disease produces no signs apart from a ‘wheeze’ throughout the chest. In serve cases
                 the patient is tachypnoeic, with accessory muscle usage and there may be intercostal muscle
                 indrawing on inspiration and pursing of lips. Chest expansion is poor, lungs on x-ray will
                 look hyperinflated, and loss of cardiac and liver dullness. Patient who become insensitive to
                 CO2 are often oedematous and cyanosed. Blue Bloater (appearance bloated, plethoric and
                 cyanosed).
   Similar
 symptoms/
other disease
Investigations      •   Lung function tests (flow volume loops/spirometry) show airflow limitation.
                    •   The FEV1:FVC ratio is reduced (usually about 80%) and the PEFR is reduced. Small
                        decrease in FEV1 <15% can be due to asthma.
                    •   CXR often normal, even when disease is advanced.
                    •   High resolution CT show emphysematous bullae
                    •   Α1-Antitrypsin levels and genotype especially in premature cases/ non-smokers.
                    •   Haemoglobin levels and PCV may be elevated due to persistent hypoxaemia.
                    •   Blood gasses normal at rest (may be hypoxaemia and hypercapnia present in severe
                        cases).

T  Surgical
r Pharmaco          •   Bronchodilators (β-adrenergic agonsts or antimuscarinic agents)- salbutamol
e cological         •   Corticosteroids- prednisolone
a                   •   Antibiotics (prompt treatment shortens exacerbations)
t                   •   Antimucolytic agents (decrease sputum viscosity and exacerbations)
m                   •   Diuretic therapy (for oedematous pts)
e                   •   Oxygen therapy
n                   •   Vaccines for flu
t
     Non-            • Smoking cessation
  Pharmaco       Treatment of respiratory failure:
    logical      Type 1 respiratory failure (low PaO2, normal PaCO2) it is safe to administer as much oxygen
                 as necessary to bring up the PaO2. As this is type 2 respiratory failure (elevated PaCO2) giving
                 additional oxygen will nearly always give a rise in PaCO2, but if the PaCO2 is allowed to fall
                 below 7.25 it can cause the patient to become acidotic. So respiration need to be stimulated
                 or artifical ventilation needs to be used (Venturi mask). Also patient should be encourage to
               cough (removal of retained secretions), Respiratory support, respiratory stimulation
               (doxapram 1.5-4.0mg/ min by slow i.v. infusion), corticosteroids, antibiotics and
               bronchodilators.
               Surgery: Bullectomy, lung volume reduction surgery, single lung transplant.
               Pulmonary rehabilitation: small exercise programs which the patient can carry out at home
               (e.g. climbing stairs, walking fixed distances) these can help improve the sense of
               breathlessness and increase the patient quality of life.

   Disease     Bronchial carcinoma Pg 880
Epidemiology        This is the most common malignant tumour it the west and the third highest cause of
                       death in the UK behind heart disease and pneumonia.
                    32,000 people a year die from bronchial carcinoma in the UK
                    Male to female ratio of 3:1.
 Pathology     Bronchial carcinomas can be divided into small-cell carcinomas and non-small-cell
               carcinomas. Studies has shown that initial malignant change to presentation takes about 15
               years for adenocarcinoma, 8 years for squamous cell carcinomas and 3 years for small-cell
               carcinoma.
               Non- small-cell carcinoma: squamous or epidermoid carcinoma is the commonest type,
               accounting for 40% of all malignancies. Most commonly presents as an obstructive lesion or
               the bronchus leading to infection, often cavities (10%), cells are usually well differentiated
               but occasional anaplastic, local spread is common but mets only happen late on.
               Adenocarcinomas arises from mucous cells in the bronchial epithelium. Invasion of the
               pleura and the mediastinal lymph nodes is common, as are mets to brain and bones. About
               10% of bronchial carcinomas. Tumours relating to Occupational factors are normally
               adenocarcinomas, especially asbestos. Proportionally more common in non-smokers, in
               women, in the elderly, and in the Far east. Large cell carcinomas are less differentiated
               forms of squamous cell and adenocarcinomas. These account for 25% of all lung cancers and
               metastasize early. Bronchoalveolar cell carcinomas accounts for only 1-2% of lung
               tumours. Occurs as either solitary nodule or as a diffuse nodular lesion of multicentric
               origin.
               Small cell carcinoma: often called oat cell carcinoma accounts for 20-30% of all lung cancers.
               These tumours arise from the endocrine cell (Kulchitsky cells), cell are members of the
               APUD, which explains why large numbers of polypeptide hormones are secreted by these
               tumours. Some of these hormones feeds back on the endocrine cells causing them to grow.
               They have early spread, rapidly growing and highly malignant and are normally inoperable
               at presentation.
Aetiology/RF       - Cigarette smoking,
                   - Higher incident in urban than in rural areas.
                   - Passive smoking,
               Occupational factors (asbestos, arsenic, chromium, iron oxide, petroleum products and oils,
               coal tar, products of coal combustion, and radiation),
   Signs/           Cough(41%)
 symptoms           Chest pain (22%)(usually described as fullness and pressure in chest. Sometimes
                       pleuritic if it had invaded the pleura and ribs)
                    Haemoptysis (7%)
                    Weight loss (<5%)
                    Shortness of breath (<5%)
                    Hoarseness (<5%)
                    Distant spread (<5%).
               On examination:
                    Often no abnormal physical signs. Enlarged supraclavicular lymph node maybe
                       present. There may be signs of a pleural effusion or of lobar collapse.
               Direct spread: carcinoma in the apex of the lung can involve the lower part of the brachial
                 plexus (C8,T1 and T2) causing serve pain in the lower shoulder and down the inner surface
                 of the arm (Pancoast ‘s Tumour). Sympathetic nerve can be involved causing Horner’s
                 syndrome. It can also effect the phrenic nerve (paralysis of hemi-diaphragm), the
                 oesophagus (progressive dysphagia, producing pericardial effusion and malignant
                 dysrhythmias).
   Similar
 symptoms/
other disease
Investigations          Chest x-ray: Most carcinoma will be visible of chest x-rays. Lateral views are good to
                         assess the hilum and to see lymph node involvement. Carcinomas causing partial
                         obstruction usually give rise to secondary pneumonia which can be seen on a chest
                         x-ray. Bronchial tumours present normally as round shadows on a chest x-ray. The
                         edge of the tumour is normally fluffy or spiked appearance, though sometime it may
                         be entirely smooth with cavitations. Also large pleural effusions will be present.
                     CT: is useful for identifying disease in the mediastinum such as enlarged lymph
                         nodes. (PET scan has become the investigation of choice for assessment of the
                         mediastinum. It is also good at looking for secondary spread of tumours and to see if
                         the other lung is involved. Poor tool for looking for whether nodes are involved.
                         When a CT scan is carried out it should include the liver, brain and adrenal glands as
                         common sites of metastases.
                     Fibreoptic bronchoscopy: used to define bronchial anatomy and to obtain biopsy and
                         cytological specimens.
                     Percutaneous aspiration and biopsy: Peripheral lung lesion can’t be seen by
                         fibreoptic bronchoscopy and sample may be obtained by direct aspiration or biopsy
                         through the chest wall under appropriate X-ray or CT screening
                 Other investigations: FBC to assess for anaemia, liver biochemistry, hypercalcaemia and
                 hyponatraemia. LFTS to assess liver function.
T  Surgical          It can be curative in non-small-cell carcinoma, but only 5-10% of cases are suitable
r                        for resection and about 70% survive for 5 years. Not normally offered to anyone
e                        over the age of 65 years as the operative mortality rate exceeds the 5 years survival
a                        rate. Pneumonectomy (if the carcinoma involves the first 2cm of either of the
t                        bronchus the tumour is inoperable as there would be insufficient resection margins
m                        for pneumonectomy)
e Pharmaco           Radiation therapy for cure: in patients who are fit and well and who have slow
n cological              growing squamous carcinoma, high-dose radiotherapy (65 Gy or 6500 rads) can
t                        produce good results. Treatment of choice if surgery is declined. Poor lung function
                         is a relative contraindication for radiotherapy.
                     Radiation treatment for symptoms: Bone pain, haemoptysis and superior vena cave
                         obstruction respond favourably to irradiation in the short term. Combination of
                         chemo and radiotherapy improves response rate and extends median survival in
                         non-small-cell carcinoma.
                     Laser therapy, endobronchial irradiation and tracheobronchial stents: used in cases of
                         inoperable lung cancer in selected patients with tracheobronchial narrowing from
                         intraluminal tumours or extrinsic compression. Causing problems with the patients
                         breathing, causing bleeding and infections.
     Non-            Palliative care: is done to allow the patient to remain as active and independent as
   Pharmaco              possible. Lung cancer patients manage better than people with other types of
    logical              cancers but they die faster when the reach the terminal phase. Prednisolone can be
                         given (15mg daily) to improve appetite. Morphine or diamorphine can be given
                         regularly for pain. Laxatives can be given as patient on opioids are more likely to get
                         constipated. Short course of radiotherapy can be given to help reduce bone pain,
                         haemoptysis or serve cough.
   Disease       Pneumothorax Pg 886/914
Epidemiology     Spontaneous pneumothorax is commonest in young males, male to female ratio is 6:1.
 Pathology       It can be spontaneous or occur as a result of trauma to the chest. A spontaneous
                 pneumothorax Is caused by the rupture of a pleural bleb, usually apical and is though to be
                 to congential defects in the connective tissue of the alveolar walls. Both lungs are affected
                 with equal frequency.
                 Tension pneumothorax: is when air is sucked into the pleural space during inspiration but
                 not expelled during expiration. Usually involves a valvular mechanism. This means that the
                 pressure remains positive though out breathing deflating the lungs further, this causes a
                 mediastinum shift and venous return to the heart decrease, with increasing cardiac and
                 respiratory embarrassment.
                 Pneumothorax: the pressure in the pleural space is negative, but once a communication with
                 the outside world. The elastic recoil in the lungs cause the lungs to partially deflates. If the
                 communication is kept open a bronchopleural fistula is made.
Aetiology/RF     Spontaneous pneumothorax:
                       In patients over the age of 40,
                       COPD
                 Rare causes: bronchial asthma, carcinoma, a lung abscess breaking down and leading to
                 bronchopleural fistula, serve pulmonary fibrosis with cyst formation.
   Signs/              Sudden onset of unilateral pleuritic pain,
 symptoms              Progressively increasing breathlessness,
                       May develop tachycardia and develop pallor if pneumothorax is large.
                 Signs:
                       Chest wall movement reduced affected side, mediastinal displacement away from
                         lesion (large pneumothorax), Percussion hyperresonant, Breath sounds reduced or
                         absent , vocal resonance (reduced or absent)
                 Examination findings:
                       Small pneumothorax: Small rim of air, best seen of expiratory x-ray,<20% of
                         radiographic volume,
                       Medium pneumothorax: definite 20-50% of radiographic volume.
                       Large pneumothorax: >obvious 50% of radiographic volume, some shift of trachea
                         and mediastinum,
                       Tension pneumothorax: Lung grossly deflated, marked deviation of trachea and
                         mediastinum
   Similar
 symptoms/
other disease
Investigations          CXR
                        Bloods
T  Surgical             Aspiration of air
r                       Intercostal drainage
e                       pleurectomy (no recurrence) or talc pleurodesis (some recurrence).
a Pharmaco
t cological
m    Non-               Small pneumothorax: Resume normal activities but avoid strenuous exercise.
e Pharmaco               Observe at 2 weekly intervals until air reabsorbed.
n   logical             Medium pneumothorax/large pneumothorax/ tension pneumothorax: aspirate air. If
t                        no recurrence resume normal activities but avoid strenuous exercise. Observe at 2
                         weekly intervals until air reabsorbed. If recurrence insert intercostal drainage tube
                         with underwater seal for 2-3 days. Re-expansion tube not bubbling remove tube and
                         then re-x-ray to exclude recurrence. If tube was still bubbling means pneumothorax
                         remains so surgery is required. Two options here pleurectomy (no recurrence) or
                         talc pleurodesis (some recurrence).

   Disease       Unilateral pleural effusion Pg 885/655
Epidemiology
 Pathology       Pleural effusion is an excessive accumulation of fluid in the pleural space.
                 Transudates: can be bilateral, but are often larger on the right side. The protein content is
                 less than 30g/L and the lactic dehydrogenase is less than 200IU/L. The causes for
                 transudate is: heart failure, hypoproteinaemia (e.g. nephrotic syndrome), constrictive
                 pericarditis, hypothyroidism, ovarian tumours producing right-sided pleural effusion
                 (Meigs’ syndrome).
                 Exudates: the protein content of exudates is >30g/l and the lactic dehydrogenase is 200
                 IU/L. Cause include: bacterial pneumonia, carcinoma of the bronchus and pulmonary
                 infarction (fluid maybe blood stained common), tuberculosis, connective tissues disease,
                 post-myocardial infarction syndrome (rare), acute pancreatitis (high amylase content)
                 (rare), mesothelioma (rare), sarcoidosis (very rare).
Aetiology/RF
   Signs/        Signs: chest wall movement effect side reduced, mediastinal displacement away from lesion
 symptoms        (in massive effusion), Percussion note stony dull, Breath sounds (vesicular, reduced or
                 absent), Vocal resonance (reduced or absent).
                 Can be detected on X-ray when there is 300ml or more of fluid or can be detected clinically
                 when there is 500ml or more in the chest. The chest x-ray appearance range from
                 obliteration of the costophrenic angle to dense homogeneous shadowing occupying part or
                 all of the hemithorax.
   Similar
 symptoms/
other disease
Investigations          Chest X-ray,
                        Respiratory examination
                        Need to work out if it is transudate or exudate, so need to do a pleural aspiration. If a
                         simple aspiration didn’t confirm diagnosis you may need to do a pleural biopsy.
T  Surgical             Surgical drainage of empyema mandatory
r Pharmaco
e cological
a    Non-        Treatment involves treating the underlying cause/condition, unless the fluid is purulent
t Pharmaco       (empyema) in which case drainage is mandatory.
m   logical
e
n
t

   Disease       Lobar pneumonia Pg 857
Epidemiology     Pneumonia can occur in any individual who is seriously ill, both in adults and in children. It
                 also occurs especially:

                 • At the extremes of life - neonates, the elderly
                 • In patients with pre-existing lung disease - chronic bronchitis, bronchiectasis, fibrosis,
                         carcinoma
                 • After abdominal operations
                 • In the compromised host, including patients with AIDS

  Pathology          •   ‘Inflammation of the substance of the lungs’- usually caused by bacteria
                     •   Can be classified by site- whole of one or more lobes affected (lobar), or diffuse when
                         they primarily affect the lobules of the lung in association with bronchi and
                          bronchioles (bronchopneumonia)
Aetiology/RF     Aetiological factor can be found in 75% of cases:
                 Bacteria- staph pneumoniae, mycoplasma pneumonia, flu A, haemophilus influenza,
                 chlamydia psittaci, chlamydia pneumonae, staphylococcus aureus, Q fever, legionella
                 pneumophilia, pseudomonas aeruginosa, etc etc
                 Chemical causes e.g. aspiration of vomit
                 Radiotherapy
                 Allergic mechanisms
                 Mycobacterium tuberculosis- classified differently as it has a different mode of presentation
                 and its treatment is different from that of other infective agents.
                 Precipitating factors:
                     • Strep pneumonae- follows viral infection (flu)
                     • Hospitalised ‘ill’ patients often with gram negative bacteria
                     • Cigarette smoking (strongest independent risk factor)
                     • Alcohol excess
                     • Bronchiectasis
                     • Bronchial obstruction (e.g. carcinoma)- occasionally associated with infection with
                          ‘non- pathogenic’ organisms
                     • Immunosuppression (e.g. AIDS)
                     • I.V. drug users- staph aureus
                     • Inhalation from oesophageal obstruction
   Signs/            • Preceding history of viral illness (in most common form from strep pneumonae)
 symptoms            • Pt rapidly becomes ill, with a high temperature (up to 39.5)
                     • Pleuritic pain
                     • Dry cough
                     • Rusty coloured sputum (after several days)
                     • May develop labial herpes simplex
                     • Pt breathes rapidly and slowly- affected side moves less and signs of consolidation
                          may be present with a pleaural rub
                 Features which indicate the severity of the pneumonia include:

                 • confusion
                 • respiratory distress
                 • cyanosis
                 The classical physical signs of pneumonic lung consolidation are:

                 • reduced percussion note
                 • bronchial breathing
                 • crackles
                 • whispering pectoriloquy
                 • pleural friction rub
                 Septicaemia should be suspected if the patient is cold, clammy and hypotensive.

                 Sputum production may not be a feature in the acute phase

   Similar
 symptoms/
other disease
Investigations      •   CXR- confirms area of consolidation (changes lag behind the clinical course, but on
                        the other hand may remain for several weeks after pt is clinically cured). Returns to
                        normal after 6 weeks (except in pts with severe airflow limitation and may
                        represent a bronchial abnormality e.g. carcinoma
                    •   FBC- CRP, WBC, ESR
                    •
T  Surgical
r Pharmaco        •   Mild community acquired- Amoxicillin/ erythromycin- then review after 48 hrs
e cological       •   Severe community acquired- IV cefuroxime and clarithromycin (if gram positive
a                     cocci or staph aureus is present then add flucloxacillin and sodium fusidate)
t    Non-      Nursing care
m Pharmaco     Physiotherapy in elderly, hydration
e   logical    Assessment
n
t

   Disease     Pulmonary Embolus Pg 442/ 784
Epidemiology   10% of clinical pulmonary emboli are fatal.
 Pathology          It is when thrombus in a vein in the systemic circulation embolises and gets into the
                       pulmonary arterial system. Where it lodges in one of the arteries. Most clots which
                       cause clinical relevant pulmonary emboli actually come from the pelvic and
                       abdominal veins, but femoral deep venous thrombosis and even occasionally axillary
                       thrombosis can be the origin of the clot.
               The emboli can be clots, but they also can be fat, tumour, amniotic fluid and foreign material.
                    When the clot lodges in one of the arteries in the lung it causes the creation of a dead
                       space which causes a decrease in gas exchange. After some hours the lung tissue
                       which isn’t getting blood flow stops producing surfactant which causes the alveoli to
                       collapse and cause further reduction in the cross section of the lung which causes a
                       reduction in the arterial bed which results in a elevation of pulmonary arterial
                       pressure and a reduction in cardiac output. The zone of lung which is cut of from it
                       arterial supply may infarct but often does not do so because oxygen continues to be
                       supplied by the bronchial circulation and the airways
Aetiology/RF   Patient factors: Age, obesity, varicose veins, long air travel, immobility, pregnancy, previous
               deep vein thrombus or pulmonary embolism, Thrombophilia, Antithrombin deficiency.
               Disease or surgical procedures: trauma or surgery of the lower limbs, pelvic or hips.
               Malignancy, cardiac failure, recent MI, infection, inflammatory bowel disease, Nephrotic
               syndrome, sickle cell anaemia.
   Signs/      Sudden onset of unexplained dyspnoea is the most common onset. People do then go and
 symptoms      develop pleuritic chest pain and haemoptysis but only once infarct has occurred. Many
               pulmonary emboli are silent but there are three typical clinical presentations.
                   - Small/medium pulmonary emboli: embolus has impacted in a terminal pulmonary
                        vessel. You get Pleuritic chest pain and breathlessness. 30% get haemoptysis
                        often 3 or more days after the initial event. Patient may be tachypnoeic with
                        localised pleural rub and often coarse crackles. Exudative pleural effusion can
                        develop. May have fever but cardio vascular examination can be normal.
                   - Massive pulmonary emboli: where sudden collapse occurs because of an acute
                        obstruction of the right ventricular outflow tract. The patient has severe central
                        chest pain and becomes shocked, pale and sweaty. The patient is tachypnoeic,
                        tachycardia with hypotension and peripheral shutdown. The JVP raised, there
                        are no abnormal chest signs. The patient will have a right heave, a gallop rhythm
                        and a widely split second heart sound.
                   - Multiple recurrent pulmonary emboli: Leads to increased breathlessness, often
                        over weeks or months. It is accompanied by weakness, syncope on exertion and
                        occasionally angina. The physical signs are due to the pulmonary hypertension
                        that has developed from multiple occlusions of the pulmonary vasculature. On
                        examination, there are signs of right ventricular overload with a right
                        ventricular heave and loud pulmonary second sound.

               This diagnostic should be considered if patient presents with unexplained cough, chest pain
                 haemoptysis, new – onset atrial fibrillation (or other tachycardia) or a sign of pulmonary
                 hypertension, if no other cause is found.
   Similar
 symptoms/
other disease
Investigations   Tests:
                 Small/medium pulmonary emboli:
                    - Chest x-ray: is often normal, but linear atelectasis or blunting of a costophrenic angle
                        is not uncommon (due to small effusions). These only develop late on. Might see
                        pulmonary infarction, the abrupt cut-off of a pulmonary artery or a translucency of
                        an underperfused distal zones are seen.
                    - ECG: is usually normal except for sinus tachycardia but sometimes atrial fib or
                        another tachyarrhythmia.
                    - Blood tests: Pulmonary infarction results in a polymorphonuclear leucocytosis, an
                        elevated ESR and increased lactate dehydrogenase levels in the serum. ALSO
                        BEFORE COMMENCING ANTICOAGULATION A THROMBOPHILIA SCREEN
                        SHOULD BE CHECKED.
                    - Plasma D-dimer: if undetectable, it excludes a diagnosis of pulmonary embolism.
                    - Radionuclide ventilation/perfusion scanning (V/Q scan): is a good and widely
                        available diagnostic test.
                    - Ultrasound scanning: can be preformed for the detection of clots in pelvic or
                        iliofemoral veins.
                    - Spiral CT scans: with intravenous contrast show good sensitivity and specificity for
                        medium- sized pulmonary emboli. New multislice CT machines have high
                        sensitivities for even small thrombi.
                    - MR imaging; gives similar results and is used if CT angiography is contraindicated
                 Massive pulmonary emboli:
                    - Chest x-ray: may show pulmonary oligaemia. Sometimes with dilatation of the
                        pulmonary artery in the hila.
                    - ECG: shows right atrial dilation with tall peaked P waves in lead 2. Right axis
                        deviation (right ventricular strain and dilation). Some degree of RBB.
                    - Blood gases: arterial hypoxaemia with a low arterial CO2 level.
                    - Echocardiography: vigorously contraction left ventricle will be seen and occasionally
                        a dilated right ventricle and a clot in the right ventricular outflow tract.
                    - Pulmonary angiography: is sometimes undertaken if surgery is considered in acute
                        massive embolisms.
                 Multiple recurrent pulmonary emboli:
                    - Chest x-ray: may be normal. Enlarged pulmonary arterioles with oligaemic lung
                        fields indicate advanced disease.
                    - ECG: can be normal or show signs of pulmonary hypertension.
                    - Leg imaging: with ultrasound and venography my show thrombi.
                    V/Q: scan may show evidence of pulmonary infarcts.
T  Surgical
r Pharmaco
e cological
a    Non-        Acute management:
t Pharmaco          - All patients should be given high-flow oxygen (60-100%) unless they have
m   logical             significant lung disease.
e                   - In cases where patient need the pumping of their right heart improving give them IV
n                       fluids and inotropic agents.
t                   - Surgical embolectomy is rarely necessary but there may be no alternative when the
                        haemodynamic circumstances are very serve.
                 Prevention of further emboli:
                 Low molecular weight heparin is given along with oral anticoagulants. When the INR has
                 reached the required value the low molecular weight heparin is tapered off. The oral
                 anticoagulants are carried on for 6weeks to 6 months, depending on likely hood of PE
                 recurring. If PE’s keep recurring lifelong anticoagulation is indicated. Sometimes physical
                 methods are required to prevent further emboli (recurrent emboli or high risk patients).
                 The most common way for this is an insertion of a filter in the vena cava via the femoral vein
                 to above the level of the renal artery.

   Disease       Peripheral vascular disease Pg 805
Epidemiology     It is present in about 7% of middle aged men and 4.5% of middle-aged women. These
                 patients are more likely to die of MI or stroke than lose the leg.
  Pathology      It is caused by atherosclerosis and usually affects the aorto-iliac or infra-inguinal arteries.
                 This leads to leg ischaemia in serve cases, which can develop into gangrene and the loss of
                 limb.
                 Acute limb ischaemia:
                 May occur because of embolic or thrombotic disease. Embolic disease is commonly due to
                 cardiac thrombus and cardiac arrhythmias. Can be also caused by emboli secondary to
                 aneurysms thrombus or thrombus on atherosclerotic plaques. Thrombotic disease is now
                 the more common cause of acute limb ischaemia. Examples are: thrombus may form on a
                 chronic atherosclerotic plaque, may occur in normal vessels if patient are hypercoagulable
                 (malignancy or thrombophilia defects), prosthetic or venous grafts.
Aetiology/RF           Smoking,
                       Diabetes,
                       Hypercholesterolaemia,
                       Hypertension
                 Premature atherosclerosis in patients aged <45 years may be associated with thrombophilia
                 and hyper-homocysteinaemia.
   Signs/        Chronic limb ischaemia:
 symptoms             - On exercise patients will complain of severe cramp (usually in calf) which resolves
                          when they stop walking. Pain often worse up hill. Pain never occurs at rest. This is
                          called intermittent claudication. Patients may also get the pain in their buttocks
                          and thigh, and can be associated with male impotence (Leriche syndrome). Can
                          appear in both legs usually worse in one. If patient get unremitting pain in the foot,
                          which stops the patient sleeping. It is called claudication. Patient say they can
                          relieve it by dangling foot over side of bed. Can develop ulceration or necrosis of the
                          tissue (gangrene).
                 Acute limb ischaemia:
                 Patients will complain of the five Ps. The pain is usually unbearable and normally requires
                 opioids for relief.

                 On examination:
                 Chronic limb ischaemia:
                 The lower limbs are cold with dry skin and lack of hair. Pulses may be diminished or absent.
                 Ulceration may occur in association with dark discolouration of the toes or gangrene.
                 Acute limb ischaemia:
                 The skin is cold with mottling or marbling. Pulses are diminished or absent. The sensation
                 and movement of the leg are reduced in severe ischaemia. Patients may develop a
                 compartment syndrome with pain in the calf on compression.
   Similar
 symptoms/
other disease
Investigations   In both forms of the disease the same test is run. It is called a ABPI (ankle branchial pressure
                 index), this is where the blood pressure in the brachial artery is compared to the pressure of
               arteries in the foot (dorsalis pedis or the posterior tibial artery). The reading tells you how
               much PVD there is, a normal reading is >1, <0.9 is abnormal, 0.5-0.9 is claudication and < 0.5
               is critical ischaemia. The sensitivity of the test can be improved by a fall in ABPI after
               exercise. You can get a false reading in diabetic or renal disease, as the reading will be false
               raised.
T  Surgical
r Pharmaco
e cological
a    Non-      Chronic limb ischaemia:
t Pharmaco     Medical management:
m   logical    Need aggressive risk factor management (e.g. stop smoking etc). Diabetics should have
e              regular chiropody appointments and diabetic management. Cholesterol should be reduced.
n              Aspirin given to patients to reduce risk of MI or stroke. Exercise can help with improving
t              quality of life and walking distance.
               Surgical/radiological:
               Only considered in patients who risk factors have been addressed and who lifestyle is
               disabled by their symptoms. Options which are available are percutaneous transluminal
               angioplasty, stents can be also put in at the same time as this is carried out. Bypass
               procedures may be preformed using Dacron, polytetrafluroethylene (PTFE) or autologous
               veins. In serve cases of ischaemia an amputation may be the only option. 70% of below
               knee and 30% of above knee amputations achieve full mobility.

               Acute limb ischaemia:
               Medical management:
               The management is dependent on the degree of ischaemia. Patients who are showing
               improvement may get treated with heparin, and the underlying cause needs to be treated. If
               patient had emboli following MI or AF need long term warfarin.
               Surgical/radiological:
               Patients showing mild/moderate ischaemic symptoms due to occluded graft may need graft
               thrombolysis, or angioplasty. A graft maybe required if occlusion of a popliteal aneurysm
               or acute-on-chronic lower limb arterial disease. When limb is revascularized, patients may
               develop compartment syndrome due to the release of the toxins which back up behind the
               thrombus. Amputation my be required if serve ischaemia.

   Disease     Abdominal aortic aneurism Pg 807/808?
Epidemiology       Incidence increases with age, being present in about 5% of the population >60 years.
                     Five times more common in men. One in four children of anyone affected will have
                     one.
 Pathology         Occurs most commonly below renal arteries (infrarenal). Aneurysms may occur
                     secondary to atherosclerosis infection (syphilis, Escherichia coli, Salmonella) and
                     trauma or may be genetic (Marfan’ s syndrome, Ehlers-Danlos syndrome).
Aetiology/RF
   Signs/           Most aneurysms are asymptomatic and area found on routine abdominal
 symptoms            examination, plain x-ray or during urological investigations.
                   Rapid expansion or rupture of AAA may cause severe pain (epigastric pain radiating
                     to the back).
                   A ruptured AAA causes hypotension, tachycardia, profound anaemia and sudden
                     death. Gradual erosion of the vertebral bodies can cause non-specific back pain.
                     Aneurysm may embolise distally. Inflammatory aneurysm can obstruct adjacent
                     structures e.g. ureter, duodenum and vena cava.
               On Examination:
                   In overweight patients there may be no overt signs. An aneurysm is suspected if a
                     pulsatile, expansile abdominal mass is felt. If patient presents with this check for
                         popliteal aneurysms.
                     
   Similar
 symptoms/
other disease
Investigations          An AAA is first assessed by ultrasound. CT is more accurate and relates the
                         anatomical relationship to the renal and visceral vessels.
T  Surgical
r Pharmaco
e cological
a    Non-        The management of an asymptomatic aneurysm depends on the risk and conservative
t Pharmaco       management. Medical:
m   logical      People need careful control of hypertension, to stop smoking and to have lipid-lowering
e                medication. If patient has AAA <5.5cm they are followed up with regular ultrasound
n                surveillance.
t                Surgery/radiography:
                 The UK small aneurysm trial indicated surgery should be offered to anyone with a AAA
                 which is ≥ 5.5 cm diameter, expanding >1cm/year and/or symptomatic. The surgical options
                 are:
                     - Repair of abdominal aortic aneurysm: standard therapy is open surgical repair with
                         insertion of a Dacron or Gore-Tex graft.
                     - Endovascular stent: this is where a stent is inserted up though the femoral or iliac
                         arteries.
                 Laparoscopic surgery: same procedure as open repair. But is associated with short hospital
                 stay but is a longer operation. The technique can be taken HALS (Hand assisted laparoscopic
                 surgery) or TLS (total laparoscopic surgery).

   Disease       Varicose veins Pg 809
Epidemiology     Varicose veins occur in young adults and incidence increases with age to 80% at 60 years.
                 Women are affected more frequently than men; in a study of people aged 35-70 the
                 prevalence of varicose veins was:

                 • 17% in men
                 • 31% in women

  Pathology      Varicose veins are dilated, tortuous veins in the leg.

                 Most varicose veins are primary; the remainder are secondary to other disorders such as
                 deep venous thrombosis or pelvic occlusion.

                 Prominent varicosities usually develop slowly, over a period of 10-20 years. In most cases,
                 the process begins in the groin with failure of the sapheno-femoral valve.

                 The long saphenous system is involved in 90% of cases; the short system, in 10%

                 It is currently thought that the wall of the vein is weak in patients with varicose veins and
                 that valvular incompentence follows rather than causes the dilatation of the vein.

                 This theory is supported by the observation that early dilatation is usually distal to an
                 incompetent valve not proximal as might be expected if the damaged were caused by a
                 descending valve incompetence.
Aetiology/RF     Congenital:

                 • Absence of valves in the iliac veins
                 • Abnormal vein wall elasticity
                 • Arteriovenous fistulae e.g. Robertson's giant limb

                 Acquired:

                 • Obesity in women (but not in men)
                 • Prolonged standing
                 • Parity - women are affected six times more often than men, the majority of cases following
                        a second or third pregnancy;
                 Important factors may include:
                     Impaired venous return, due to pressure on the iliac veins from the pregnant uterus
                     High level of progesterone which alters collagen structure, sometimes irreversibly,
                        and relaxes smooth muscle
                 • Previous deep vein thrombosis - valves damaged when the veins recanalise

   Signs/        Symptoms commonly associated with varicose veins are
 symptoms
                 • disfigurement:
                 ◦          patients are frequently disturbed by the poor cosmetic appearance of their legs
                 ◦          both their concern and their symptoms may worsen in the summer when the legs
                                  are warm and exposed
                 • pain:
                 ◦          legs frequently ache, especially after prolonged standing
                 ◦          patients often describe a dull, heavy, "burning" sensation that becomes more
                                  severe as the day progresses
                 ◦          in women, symptoms may worsen in the few days prior to menstruation
                 • itching:
                 ◦          the skin over the varices may itch
                 ◦          may be associated with varicose eczema
                 • heaviness
                 • worry:
                 ◦          patients may present because of concern about possible complications such as
                                  ulceration
                 Examination:

                 • varices appear on standing and disappear when recumbent
                 • positive Brodie-Trendelenburg test
                 • doppler flow studies identify 'backflow' through incompetent valves

   Similar
 symptoms/
other disease
Investigations   Ideally all patients with varicose veins would have colour duplex ultrasound scanning to
                 determine the characteristics of blood flow in the leg. Unfortunately this is not possible and
                 so duplex scanning is reserved for the following groups of patients with:

                 •   Recurrent varicose veins
                 •   A history of superficial thrombophlebitis
                 •   A history of DVT
                 •   Varicose eczema
                 •   Haemosiderin discolouration
                • Lipodematosclerosis
                • Venous ulceration

T   Surgical    Varicose veins are asymptomatic in the majority of people, yet remain one of the most
r               common reasons for surgical referral in the developed world.
e               • Sclerotherapy - permanent obliteration of varices
a               • Open operation - removal of varices with ligation of incompetent perforaters
t               Alternatives to the current operative techniques are being introduced
m               • Endovenous obliteration using radiofrequency (diathermy) or laser has been devised to
e                      close the long saphenous vein, an alternative to the traditional "stripping."
n               • "powered phlebectomy" - this is another new technique that obviates the need for
t                      multiple "phlebectomies" to avulse calf varicosities, thus giving a more cosmetically
                       favourable outcome.
                •      Minimally invasive approach uses an illuminator under the skin to accurately target
                       the vein, which is removed by suction under direct vision
                Leaves the patient without multiple stab incision scars and potentially lowers the risk of
                postoperative infection
    Pharmaco
    cological
      Non-      About one-third of cases can be managed by offering common sense advice as to how to take
    Pharmaco    care for their legs.
     logical    Complications caused by the varicose ulcers themselves include:

                • haemorrhage:
                                bleeding may be profuse because of the high venous pressure
                • superficial thrombophlebitis
                Complications caused by associated venous hypertension include:

                •   ankle oedema
                •   varicose eczema
                •   lipodermatosclerosis:
                •   atrophie blanche
                •   severe excoriation from scratching
                •   venous ulceration

				
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