CDM revision SEM 1 Flashcards
What is the criteria for neutropenic sepsis and what. prophylaxis and treatment is given to a suspect or known case?
Neutropenic sepsis is a relatively common complication of cancer therapy, usually as a consequence of chemotherapy. It most commonly occurs 7-14 days after chemotherapy. It may be defined as a neutrophil count of < 0.5 * 109 in a patient who is having anticancer treatment and has one of the following:
a temperature higher than 38ºC or
other signs or symptoms consistent with clinically significant sepsis
Prophylaxis
if it is anticipated that patients are likely to have a neutrophil count of < 0.5 * 109 as a consequence of their treatment they should be offered a fluoroquinolone
Management
antibiotics must be started immediately, do not wait for the WBC
NICE recommends starting empirical antibiotic therapy with piperacillin with tazobactam (Tazocin) immediately
many units add vancomycin if the patient has central venous access but NICE do not support this approach
following this initial treatment patients are usually assessed by a specialist and risk-stratified to see if they may be able to have outpatient treatment
if patients are still febrile and unwell after 48 hours an alternative antibiotic such as meropenem is often prescribed +/- vancomycin
if patients are not responding after 4-6 days the Christie guidelines suggest ordering investigations for fungal infections (e.g. HRCT), rather than just starting therapy antifungal therapy blindly
there may be a role for G-CSF in selected patients
What are the risk factors for developing DVT?
General increased risk with advancing age obesity family history of VTE pregnancy (especially puerperium) immobility hospitalisation anaesthesia central venous catheter: femoral >> subclavian
Underlying conditions malignancy thrombophilia: e.g. Activated protein C resistance, protein C and S deficiency heart failure antiphospholipid syndrome Behcet's polycythaemia nephrotic syndrome sickle cell disease paroxysmal nocturnal haemoglobinuria hyperviscosity syndrome homocystinuria
Medication
combined oral contraceptive pill: 3rd generation more than 2nd generation
hormone replacement therapy: the risk of VTE is higher in women taking oestrogen + progestogen preparations compared to those taking oestrogen-only preparations
raloxifene and tamoxifen
antipsychotics (especially olanzapine) have recently been shown to be a risk factor
What is the commonest non-Hodgkins lymphoma in the UK?
Diffuse large B cell lymphoma is by far the most common form of non-Hodgkin lymphoma (NHL) in the UK. It comprises around 40% of the total lymphoma cases. It is a high-grade tumour (i.e. aggressive) but typically responds better to treatment than some of the more indolent lymphomas.
How can Hodgkin’s and Non Hodgkin’s lymphoma be differentiated clinically?
While differentiating Hodgkin’s lymphoma from non-Hodgkin’s lymphoma is done by biopsy certain elements of the clinical presentation can help point towards one rather than the other.
Lymphadenopathy in Hodgkin’s lymphoma can experience alcohol-induced pain in the node
‘B’ symptoms typically occur earlier in Hodgkin’s lymphoma and later in non-Hodgkin’s lymphoma
Extra-nodal disease is much more common in non-Hodgkin’s lymphoma than in Hodgkin’s lymphoma
How can Lymphoma’s be Investigated and what is the characteristic biopsy finding in Burkitt’s lymphoma?
Excisional node biopsy is the diagnostic investigation of choice (certain subtypes will have a classical appearance on biopsy such as Burkitt’s lymphoma having a ‘starry sky’ appearance)
CT chest, abdomen and pelvis (to assess staging)
HIV test (often performed as this is a risk factor for non-Hodgkin’s lymphoma)
FBC and blood film (patient may have a normocytic anaemia and can help rule out other haematological malignancy such as leukaemia)
ESR (useful as a prognostic indicator)
LDH (a marker of cell turnover, useful as a prognostic indicator)
Other investigations can be ordered as the clinical picture indicates (LFT’s if liver metastasis suspected, PET CT or bone marrow biopsy to look for bone involvement, LP if neurological symptoms)
What are the laboratory findings in beta thalassemia?
The thalassaemias are a group of genetic disorders characterised by a reduced production rate of either alpha or beta chains. Beta-thalassaemia trait is an autosomal recessive condition characterised by a mild hypochromic, microcytic anaemia. It is usually asymptomatic
Features mild hypochromic, microcytic anaemia - microcytosis is characteristically disproportionate to the anaemia HbA2 raised (> 3.5%)
What are the types and causes of macrocytic anemia and what the features of megaloblastic anemia?
Macrocytic anaemia can be divided into causes associated with a megaloblastic bone marrow and those with a normoblastic bone marrow
Megaloblastic causes
vitamin B12 deficiency
folate deficiency
Normoblastic causes
alcohol liver disease hypothyroidism pregnancy reticulocytosis myelodysplasia drugs: cytotoxics
symptoms of anaemia, glossitis, a macrocytosis and hyper-segmented neutrophils on the blood film. This is typical of a megaloblastic anaemia such as B12 or folate deficiency anaemia. Another key feature of a megaloblastic anaemia is the presence of megaloblasts and giant metamyelocytes within the bone marrow. Following a full blood count, a blood film is the suggested second-line test for megaloblastic anaemia (as per BMJ best practice). It is also common practice to test for haematinics as this may reveal low B12 or folate levels and hence identify the cause of macrocytosis.
What are the causes of hyperkalemia and the ecg changes seen?
ECG changes seen in hyperkalaemia include tall-tented T waves, small P waves, widened QRS leading to a sinusoidal pattern and asystole
Causes of hyperkalaemia: acute kidney injury drugs*: potassium sparing diuretics, ACE inhibitors, angiotensin 2 receptor blockers, spironolactone, ciclosporin, heparin** metabolic acidosis Addison's disease rhabdomyolysis massive blood transfusion
What does raised ALP in the presence of normal LFT’s indicate?
Raised ALP in the presence of normal LFT’s should raise suspicion of malignancy. Particularly bone cancer/ metastases
How does hypophosphatemia present?how is it treated?
acute respiratory failure secondary to severe hypophosphataemia.
Hypophosphataemia is a common complication of insulin therapy in diabetic ketoacidosis (DKA) hence increasing the dosage of insulin is not an answer in this case. A rise in insulin causes phosphate to shift into the intracellular compartment, similar to the mechanism involved in hypophosphataemia as a result of refeeding syndrome or hyperglycaemic hyperosmolar non-ketotic coma (HONK).
Hypophosphataemia as a result of DKA treatment is usually transient and mild. Phosphate replacement therapy is rarely required unless it is severe and should be given as an infusion. Insulin therapy should never be stopped in a patient with DKA.
What are the causes and complications of hypophosphatemia?
Causes alcohol excess acute liver failure diabetic ketoacidosis refeeding syndrome primary hyperparathyroidism osteomalacia
Consequences red blood cell haemolysis white blood cell and platelet dysfunction muscle weakness and rhabdomyolysis central nervous system dysfunction
What are the causes of raised ALP?
Causes of raised alkaline phosphatase (ALP)
liver: cholestasis, hepatitis, fatty liver, neoplasia
Paget’s
osteomalacia
bone metastases
hyperparathyroidism
renal failure
physiological: pregnancy, growing children, healing fractures
The table below splits the causes according to the calcium level
Raised ALP and raised calcium Raised ALP and low calcium Bone metastases Hyperparathyroidism Osteomalacia Renal failure
What are the causes of SIADH including drug causes?
Malignancy small cell lung cancer also: pancreas, prostate Neurological stroke subarachnoid haemorrhage subdural haemorrhage meningitis/encephalitis/abscess Infections tuberculosis pneumonia Drugs sulfonylureas* SSRIs, tricyclics carbamazepine vincristine cyclophosphamide Other causes positive end-expiratory pressure (PEEP) porphyrias
What are the causes of hypocalcemia and how can it be managed?
Causes
vitamin D deficiency (osteomalacia)
chronic kidney disease
hypoparathyroidism (e.g. post thyroid/parathyroid surgery)
pseudohypoparathyroidism (target cells insensitive to PTH)
rhabdomyolysis (initial stages)
magnesium deficiency (due to end organ PTH resistance)
massive blood transfusion
acute pancreatitis
Contamination of blood samples with EDTA may also give falsely low calcium levels.
Management
acute management of severe hypocalcaemia is with intravenous replacement. The preferred method is with intravenous calcium gluconate, 10ml of 10% solution over 10 minutes
intravenous calcium chloride is more likely to cause local irritation
ECG monitoring is recommended
further management depends on the underlying cause
How does Osmotic demyelination syndrome (central pontine myelinolysis) present?
can occur due to over-correction of severe hyponatremia
to avoid this, Na+ levels are only raised by 4 to 6 mmol/l in a 24-hour period
symptoms usually occur after 2 days and are usually irreversible: dysarthria, dysphagia, paraparesis or quadriparesis, seizures, confusion, and coma
patients are awake but are unable to move or verbally communicate, also called ‘Locked-in syndrome’
How is Hypercalcemia treated?
The initial management of hypercalcaemia is rehydration with normal saline, typically 3-4 litres/day. Following rehydration bisphosphonates may be used. They typically take 2-3 days to work with maximal effect being seen at 7 days
Other options include:
calcitonin - quicker effect than bisphosphonates
steroids in sarcoidosis
Loop diuretics such as furosemide are sometimes used in hypercalcaemia, particularly in patients who cannot tolerate aggressive fluid rehydration. However, they should be used with caution as they may worsen electrolyte derangement and volume depletion.
What can cause hypernatremia and how is it managed?
Causes of hypernatraemia dehydration osmotic diuresis e.g. hyperosmolar non-ketotic diabetic coma diabetes insipidus excess IV saline
Hypernatraemia should be corrected with great caution. Although brain tissue can lose sodium and potassium rapidly, lowering of other osmolytes (and importantly water) occurs at a slower rate, predisposing to cerebral oedema, resulting in seizures, coma and death1. Although there are no clinical guidelines by NICE or Royal College of Physicians at present, it is generally accepted that a rate of no greater than 0.5 mmol/hour correction is appropriate.
What new diabetic drug can potentially be used to treated renal impairment
- In chronic kidney disease (CKD), dapagliflozin (Farxiga) reduced renal events and substantially improved overall survival, regardless of diabetes status, theDAPA-CKD trialshowed
How can CKD be classified?
Chronic kidney disease (CKD) can be defined by the presence of kidney damage or reduced kidney function for three or more months.
Chronic kidney disease (CKD) is classified using a combination of estimated glomerular filtration rate (eGFR) and urinaryalbumin:creatinine ratio(ACR).
- Increased ACR is associated with increased risk of adverse outcomes.
- Decreased GFR is associated with increased risk of adverse outcomes.
- Increased ACR and decreased GFR in combination multiply the risk of adverse outcomes.
How can proteinuria be measured?
ACR>30
What is Alport’s syndrome?
Chronic kidney disease (CKD) is classified using a combination of estimated glomerular filtration rate (eGFR) and urinaryalbumin:creatinine ratio(ACR).
- Increased ACR is associated with increased risk of adverse outcomes.
- Decreased GFR is associated with increased risk of adverse outcomes.
- Increased ACR and decreased GFR in combination multiply the risk of adverse outcomes.
COL4A5 is on thechromosome), so mutations in it can cause[X-linked])[Alport syndrome
COL4A3 and A4 are on[autosomes, meaning non-[sex chromosomes]and mutations in these cause either[autosomal recessive]
[Alport syndrome] which is also early onset, or[autosomal dominant][Alport syndrome](, which causes late onset disease.
• For diagnosis, Alport syndrome is typically suspected when there are clinical signs like gross hematuria or if there are vision or hearing problems, or microscopic hematuria with no apparent cause.
- To confirm the diagnosis, a kidney or skin biopsy is often analyzed by immunohistochemistry, meaning a labelled antibody is applied to a biopsy sample on a slide.
- The treatment for Alport syndrome usually focuses on the symptoms.
- Proteinuria is treated with angiotensin converting enzyme inhibitors and/or angiotensin receptor blockers because there is evidence that this prevents progression to kidney failure.
- Anterior lenticonus can be treated with a replacement lens, and Kidney failure necessitates dialysis or even kidney transplant.
What are the side effects of hemodialysis?
hypotension arrhythmia muscle cramps nausea and vomiting headache air embolism seizure disequilibrium syndrome hemolysis
What are the complications for peritoneal dialysis
peritonitis catheter non function hyperlipidemia risk of hernias weight gain and hyperglycaemia
What are the Drug class Drug examples Mechanism of action SEs Contraindications
of common oral hypoglycaemic agents?
Drug class Drug examples Mechanism of action SEs Contraindications Biguanide Metformin
Other uses of metformin:
PCOS
NAFLD
Activates the AMP activated protein kinase (AMPK)
Increases insulin sensitivity
Decreases hepatic gluconeogenesis
GI side effects (can change to modified release if this is the case) - intolerable in 20% of people
Reduced vitamin b12 absorption
Lactic acidosis – this is rare. Occurs in severe liver disease/renal failure
No hypos, no weight gain
CKD – stop metofmrin if creatinine >150 or eGFR <30
Stop metformin if recent AKI, severe dehydration, recent MI (risk of lactic acidosis)
Sulfonylurea
Glomiperide, gliclazide
Increase pancreatic insulin secretion
Hypos
Increased appetite and weight gain
Rarer: SIADH Cholestatic liver dysfunction Peripheral neuropathy BM suppression Avoid in breast feeding and pregnancy Thiazolidinediones Pioglitazone Reduce peripheral insulin resistance Weight gain Liver impairment (LFTs need to be monitored) Fluid retention Bladder cancer Heart failure (due to fluid retention) DPP4-inhibitor Sitagliptin, alogliptin, vildagliptin - oral DPP4 inhibitors inhibit the breakdown of GLP1 (GLP1 = glucagon like peptide 1, it increases insulin secretin and inhibits glucagon secretion) Does not cause weight gain, does not cause hypos
Pancreatitis
SGLT2- inhibitor
Empaglafiozine, dapagliflozin, canagliflozin
Inhibits sodium glucose co-transporter 2 (SGLT2) in the kidney – increases urinary glucose excretion
Risk of DKA – with normal/mildly elevated blood glucose—therefore need to warn patients of symptoms of DKA (e.g. Rapid weight loss, N, V, fast breathing, sleepiness, sweet breath)
Fouriner’s gangrene
If had previous DKA GLP 1 mimetic Exenatide – given Subcut Dulaglutide NICE guidance – used in obese patients only (BMI above 35)
GLP1 is a hormone released by small intestine in response to glucose.
These drugs increase insulin secretion, inhibit glucagon secretion, slow gastric emptying
Weight loss (advantage)
Nausea, vomiting
How to separate pre-renal uraemia from acute tubular necrosis
Prerenal uraemia - kidneys hold on to sodium to preserve volume
What are the causes, signs and symptoms of hypokalaemia?
Symptoms include weakness, leg cramps, palpitations secondary to cardiac arrhythmias and ascending paralysis.
Causes can be secondary to:
1.) Increased potassium loss:
Drugs: thiazides, loop diuretics, laxatives, glucocorticoids, antibiotics
GI losses: diarrhoea, vomiting, ileostomy
Renal causes: dialysis
Endocrine disorders: hyperaldosteronism, Cushing’s syndrome
2.) Trans-cellular shift Insulin/glucose therapy Salbutamol Theophylline Metabolic alkalosis
- ) Decreased potassium intake
- ) Magnesium depletion (associated with increased potassium loss)
ECG changes seen in hypokalaemia include:
U waves
T wave flattening
ST segment changes
Treatment of hypokalaemia depends on severity. Any causative agents should be removed. Gradual replacement of potassium via the oral route is preferred if possible.
Mild to moderate hypokalaemia 2.5 - 3.4 mmol/l can be treated with oral potassium provided the patient is not symptomatic and there are no ECG changes.
Severe hypokalaemia (<2.5mmol/l) or symptomatic hypokalaemia should be managed with IV replacement. The patient should be managed in an area where cardiac monitoring can take place. If there are no contraindications to fluid therapy (e.g. volume overload, heart failure) potassium should be diluted to low concentrations as higher concentrations can be phlebitic. The infusion rate should not exceed 20mmol/hr. In this case, 3 bags of 0.9% Saline with 40mmol KCL is the correct answer.
What is Alpha 1 anti trypsin deficiency?How does it present and how is investigated and managed?
Genetics
located on chromosome 14
inherited in an autosomal recessive / co-dominant fashion*
alleles classified by their electrophoretic mobility - M for normal, S for slow, and Z for very slow
normal = PiMM
homozygous PiSS (50% normal A1AT levels)
homozygous PiZZ (10% normal A1AT levels)
Features
patients who manifest disease usually have PiZZ genotype
lungs: panacinar emphysema, most marked in lower lobes
liver: cirrhosis and hepatocellular carcinoma in adults, cholestasis in children
Investigations
A1AT concentrations
spirometry: obstructive picture
Management
no smoking
supportive: bronchodilators, physiotherapy
intravenous alpha1-antitrypsin protein concentrates
surgery: lung volume reduction surgery, lung transplantation
What are the causes of ascites
scites is the abnormal accumulation of fluid in the abdomen.
The causes of ascites can be grouped into those with a serum-ascites albumin gradient (SAAG) <11 g/L or a gradient >11g/L as per the table below:
SAAG > 11g/L
(indicates portal hypertension) SAAG <11g/L
Liver disorders are the most common cause
cirrhosis/alcoholic liver disease
acute liver failure
liver metastases
Cardiac
right heart failure
constrictive pericarditis
Other causes Budd-Chiari syndrome portal vein thrombosis veno-occlusive disease myxoedema
SAAG <11g/L
Hypoalbuminaemia
nephrotic syndrome
severe malnutrition (e.g. Kwashiorkor)
Malignancy
peritoneal carcinomatosis
Infections
tuberculous peritonitis
Other causes pancreatitisis bowel obstruction biliary ascites postoperative lymphatic leak serositis in connective tissue diseases
What drugs are hepatotoxic?
Drug-induced liver disease is generally divided into hepatocellular, cholestatic or mixed. There is however considerable overlap, with some drugs causing a range of changes to the liver
The following drugs tend to cause a hepatocellular picture: paracetamol sodium valproate, phenytoin MAOIs halothane anti-tuberculosis: isoniazid, rifampicin, pyrazinamide statins alcohol amiodarone methyldopa nitrofurantoin
The following drugs tend to cause cholestasis (+/- hepatitis):
combined oral contraceptive pill
antibiotics: flucloxacillin, co-amoxiclav, erythromycin*
anabolic steroids, testosterones
phenothiazines: chlorpromazine, prochlorperazine
sulphonylureas
fibrates
rare reported causes: nifedipine
Liver cirrhosis
methotrexate
methyldopa
amiodarone
What is Budd chiari syndrome?
Budd-Chiari syndrome, or hepatic vein thrombosis, is usually seen in the context of underlying haematological disease or another procoagulant condition.
Causes
polycythaemia rubra vera
thrombophilia: activated protein C resistance, antithrombin III deficiency, protein C & S deficiencies
pregnancy
combined oral contraceptive pill: accounts for around 20% of cases
The features are classically a triad of:
abdominal pain: sudden onset, severe
ascites → abdominal distension
tender hepatomegaly
Investigations
ultrasound with Doppler flow studies is very sensitive and should be the initial radiological investigation
How can Ascites be managed
Management
reducing dietary sodium
fluid restriction is sometimes recommended if the sodium is < 125 mmol/L
aldosterone antagonists: e.g. spironolactone
loop diuretics are often added. Some authorities only add loop diuretics in patients who don’t respond to aldosterone agonists whereas other authorities suggest starting both types of diuretic on the first presentation of ascites
drainage if tense ascites (therapeutic abdominal paracentesis)-give albumin give prophylactic antibiotics(cipro)
large-volume paracentesis for the treatment of ascites requires albumin ‘cover’. Evidence suggests this reduces paracentesis-induced circulatory dysfunction and mortality
paracentesis induced circulatory dysfunction can occur due to large volume paracentesis (> 5 litres). It is associated with a high rate of ascites recurrence, development of hepatorenal syndrome, dilutional hyponatraemia, and high mortality rate
prophylactic antibiotics to reduce the risk of spontaneous bacterial peritonitis. NICE recommend: ‘Offer prophylactic oral ciprofloxacin or norfloxacin for people with cirrhosis and ascites with an ascitic protein of 15 g/litre or less, until the ascites has resolved’
a transjugular intrahepatic portosystemic shunt (TIPS) may be considered in some patients
What are the differentials for hepatic encephalopathy?
Patients may present similarly withacute alcoholic hepatitis
Other causes of confusion(which may be present in a patient with liver disease) and should always be considered when a patient with chronic liver disease presents confused
- Delirium – which can be secondary to many causes but often infection
- Head injury – subdural haematoma
- Alcohol withdrawal
- Drugs
What can cause an increase in conjugated and unconjugated bilirubin?
The commonest causes of raised unconjugated bilirubin in adults are:
- Gilbert’s syndrome:
- A genetic disorder where less of the enzyme that breaks down Bilirubin (UDP-glucuronyltransferase) is produced. It affects 5% of the population. There is an increase in the bilirubin often with fasting or concurrent illness.
- Confirmation of just a predominant unconjugated hyperbilirubinaemia makes the diagnosis of Gilbert’s syndrome virtually certain. This does not require any treatment and the patient can be completely reassured.
- Rarely does it cause a bilirubin above 68umol/L
- Haemolysis:
- The breakdown of red blood cells. There can by many causes for this and standard investigations for this would include: reticulocyte count, LDH, blood film, Haptoglobin, Direct coombs test
- Drug related, for example, the antibiotic Rifampicin impairs the uptake of Bilirubin
In healthy adults conjugated bilirubin is virtually absent. Levels usually start to become increased when the liver has lost approximately ½ of its excretory capacity. It is therefore usually a sign of liver disease, which may be acute or chronic in nature.
Common causes for elevated conjugated bilirubin include:
- Biliary obstruction at any level of the bile ducts
- Often secondary to gallstones in the common bile duct, but also from malignancy – commonly Cholangiocarcinoma or Pancreatic cancer
- Cholestatic drug reactions
- Potentially any drug, but commonly antibiotics such as Nitrofuratoin and Penicillin
- Autoimmune Cholestatic disease e.g. Primary Sclerosing Cholangitis (may occur at any level) and Primary Biliary Cirrhosis (intrahepatic ducts)
- Hepatitis of any origin where there is significant impairment in liver function
- Cirrhosis
What are triggers for chronic liver disease to become decompensated?
Causes of this acute:
The most likely cause of this presentation is that this man has decompensated liver disease with encephalopathy. Things which may may cause a patient to decompensate include
- Upper GI bleed
- Spontaneous bacterial peritonitis
- Infection (any source)
- Constipation
- Drugs – prescription or recreational
- Dehydration
- Alcohol – either a binge or withdrawal
- Portal vein thrombosis
What are the features of PBC and how is it treated?
common in female-damage to intrahepatic ducts
Presentation-no symptoms,itch,Sjorens,jaundice ,fatigue,poor memory
Labs-raised ALP ,raised IgM,AMA,biopsy-granulomatous lymphatic cholangitis(not needed-florid ducts, duct loss)
Exclude other causes
treatment-UDCA
Itch-Cholestyramine, rifampicin, gabapentin
Treat symptoms-fatigue
Monitering-itch,osteoporosis,cirrhosis
liver transplant
How does autoimmune hepatitis present and how is it diagnosed?
Any age
Can be precipitated by drugs such as statins, statins,nitrofurantoin
types
type 1-80%(ANA/ASMA)
type 2-<10%(liver kidney microsomal LKM,liver cystosol antibody-high risk outcome
presentation-fatigue,aneroxia,nausea,joint pain, acute hepatitis jaundice
labs raised ALT ANA/ASMA RAISED IgG usually need biopsy confirm fibrosis
Treatment-aim for normal ALT and IgG
lifelong immunosupression
-predinsolone,Azathioprine,MMF,tacrolimus,liver transplant
How does PBC present and how is it diagnosed and managed?
Inflammation and fibrosis of both intra and extra hepatic bile ducts
70-80% have IBD(UC)
symptoms-asymptomatic,fatique,itch,RUQ pain,cholangitis,jaundice and complication
labs-raised ALP,MRCP shows beads on string appearance
CT not helpful US normal
biopsy-onion skin
treatment
IBD-colonoscopy
Itch-same as PBC
manage cholangitis if causing symptoms
Complications
bone disease
cholangiocarcinoma (in 10%)
increased risk of colorectal cancer
liver transplantation
What causes Wilson’s disease how does it present and how is it managed?
Wilson’s disease is a rare progressive genetic disorder, which results in accumulation of copper in the body’s tissues. In particular it affects the brain, liver and cornea of the eyes. Untreated it may lead to liver fibrosis and cirrhosis, along with central nervous system dysfunction.
There are 500 gene mutations known about. These result in dysfunction in Wilson’s ATPase(ATP7B-helps Cu bind to ceruloplasmin and form vesicles to be excreted in the bile), which usually moves copper from along intracellular membranes in the liver. The defective ATPase results in accumulation of copper in the liver, resulting in damage. Over time as the liver becomes damaged the copper is released into the blood and causes other end organ damage.
Patients may present with:
Liver dysfunction (most common presentation):
·Decompensated liver cirrhosis
·Acute liver failure (often associated with renal failure and haemolytic anaemia)
Central nervous system (usually have established liver disease):
·Asymmetrical tremor in ½ patients with CNS dysfunction
·Poor co-ordination and clumsiness
·Speech and language problems
·Neuropsychiatric illness – commonly severe depression or neuroticbehaviours
Enlarged liver and spleen
Renal disease due to damage to distal renal tubules
hemolytic anemia
Ophthalmological
·Kayser-Fleischer ring present in 95% of those with neurological disease (seen on slit-lamp), 50% of those without. May occur in other diseases.
·Sun-flower cataracts – seen on slit lamp. Do not impair vision
Diagnosis.
Consider in any patient of any age with unusual liver or neurological abnormalities. There is no one best test for diagnosis.
Presence of Kayser-Felischer ring and low serum caeruloplasmin (<0.1g/L) is enough to establish diagnosis.
Caeruloplasmin is a protein made in the liver that stores and carries copper around the blood. This may be low in Wilson’s as copper is not able to bind to the protein causing instability. Serum Caeruloplasmin is can be affected by many factors and is not diagnostic on it’s own.
Other markers of disease include 24hour urinary copper, serum free copper and hepatic copper (liver biopsy).
A scoring system also exists to help with diagnosis.
Genetic screening is complex, many patients are compound heterozygotes (carry two different defective genes) and it can take many months to complete.
Treatment
Treatment is life-long. It involves using medication to either promote urinary excretion or to decrease intestinal absorption. The commonest medication used is D-Penicillamine.
Zinc salts,trientine,tetrathiomolybdate
Genetics are complex due to the number of gene variations, but essentially siblings (25% risk) and any offspring (0.5% risk) should be offered genetic screening.
What are grades of hepatic encephalopathy and how is it treated?
I-irritabilty
ii-confusion
iii-incoherent inappropriate behaviour, restless
iv-coma
Precipitating factors infection e.g. spontaneous bacterial peritonitis GI bleed post transjugular intrahepatic portosystemic shunt constipation drugs: sedatives, diuretics hypokalaemia renal failure increased dietary protein (uncommon)
Management
treat any underlying precipitating cause
NICE recommend lactulose first-line, with the addition of rifaximin for the secondary prophylaxis of hepatic encephalopathy
lactulose is thought to work by promoting the excretion of ammonia and increasing the metabolism of ammonia by gut bacteria
antibiotics such as rifaximin are thought to modulate the gut flora resulting in decreased ammonia production
other options include embolisation of portosystemic shunts and liver transplantation in selected patients
What are the causes of Acute liver failure?
ALF-HE defining feature
– drugs (inc paracetamol, abx and anti-epileptics), viruses (typically hepatitis A, B and E), toxins (classically mushroom poisoning, many herbal remedies are implicated), vascular causes (e.g. budd chiari or ischaemic/hrpoxic hepatitis), pregnancy-related and some miscellaneous causes e.g. acute and fulminant presentation of Wilson disease/AIH) and malignant infiltration of the liver, typically by breast cancer or lymphoma
What is the King college criteria for Emergency liver transplant?
ALF due to paracetamol
Arterial pH <7.3 after resuscitation and>24 hours since ingestion Lactate >3 mmol/L or The 3 following criteria: HE >Grade 3 Serum creatinine >300 µmol/L INR >6.5
ALF not due to paracetamol
INR >6.5 or 3 out of 5 following criteria: Aetiology: indeterminate aetiology, hepatitis, drug-induced hepatitis Age <10 years or >40 years Interval jaundice encephalopathy >7 days Bilirubin >300 µmol/L INR >3.5
What are the contraindications for liver transplant?
Medical
Untreated or progressive infection
Clinically apparent extrahepatic or metastatic malignancy
Progressive hypotension, resistant to vasopressor support
Clinically significant ARDS, FiO2 > 0.8
Fixed dilated pupils > 1 hour in the absence of thiopentone
Severe coexistent cardiopulmonary disease
HIV?
psychiatric
Multiple episodes of self harm (>5) within an established pattern of behaviour (esp. if non-drug methods used)
Consistently stated wish to die, in the absence of established mental illness
Chronic refractory schizophrenia or other mental illness, resistant to therapy
Incapacitating dementia or mental retardation
Active intravenous drug abuse or oral polydrug use
Alcohol dependence or abuse
What is the pathophysiology of Alcoholic liver disease?
Ethanol is metabolized in the liver by two pathways, resulting in an increase in the NADH/NAD ratio. The altered redox potential causes increased hepatic fatty acid synthesis with decreased fatty acid oxidation; both events lead to hepatic accumulation of fatty acid,which is then esterified to glycerides.
The changes in oxidation–reduction also impair carbohydrate and protein metabolism and are the cause of the centrilobular necrosis of the hepatic acinus that is typical of alcohol damage. TNFα release from Kupffer cells causes the release of reactive oxygen species,leading, in turn, to tissue injury and fibrosis.Acetaldehyde is formed by the oxidation of ethanol, and its effect on hepatic proteins may
well be a factor in producing liver cell damage.
n addition to fatty change, there is infiltration by polymorphonuclear leucocytes and
hepatocyte necrosis, mainly in zone 3. Dense cytoplasmic inclusions called Mallory bodies are
sometimes seen in hepatocytes and giant mitochondria are also a feature. Mallory bodies are
suggestive of, but not specific for, alcoholic damage, as they can be found in other liver
disease, such as Wilson’s disease and primary biliary cholangitis. If alcohol consumption
continues, alcoholic hepatitis may progress to cirrhosis.
How does Alcoholic liver disease present?
Alcoholic liver disease covers a spectrum of conditions:
alcoholic fatty liver disease
alcoholic hepatitis
cirrhosis
tender hepatomegaly
Selected investigation findings:
gamma-GT is characteristically elevated
the ratio of AST:ALT is normally > 2, a ratio of > 3 is strongly suggestive of acute alcoholic hepatitis
Hypoglycemias,Increased MCV,thrombocytopenia
Selected management notes for alcoholic hepatitis:
glucocorticoids (e.g. prednisolone) are often used during acute episodes of alcoholic hepatitis
Maddrey’s discriminant function (DF) is often used during acute episodes to determine who would benefit from glucocorticoid therapy
it is calculated by a formula using prothrombin time and bilirubin concentration
pentoxyphylline is also sometimes used
the STOPAH study (see reference) compared the two common treatments for alcoholic hepatitis, pentoxyphylline and prednisolone. It showed that prednisolone improved survival at 28 days and that pentoxyphylline did not improve outcomes
How is Haemochromatosis inherited and what are the genes involved?
The two known mutations of HFE are C282Y and H63D. Testing for these is simple and cheap. But there are other rare genes that may cause disease
Whilst this is an autosomal recessive condition, clinically things can be a bit more complex – this is because gene expression (penetrance) varies. E.g. just because you have two copies of the defective gene does not mean you will definitely develop the clinical condition.
- C282Y/C282Y Homozygous gives a 95% risk of iron overload
- C282Y/H63D compound heterozygotes gives around 4% risk (increased risk with increased alcohol intake, viral hepatitis)
- H63D/H63D Homozygous is least likely to cause iron overload
All these genes lead to increased intestinal absorption of iron.
What are the features of haemochromatosis?
resenting features
early symptoms include fatigue, erectile dysfunction and arthralgia (often of the hands)
‘bronze’ skin pigmentation
diabetes mellitus
liver: stigmata of chronic liver disease, hepatomegaly, cirrhosis, hepatocellular deposition)
cardiac failure (2nd to dilated cardiomyopathy)
hypogonadism (2nd to cirrhosis and pituitary dysfunction - hypogonadotrophic hypogonadism)
arthritis (especially of the hands)
Increase risk if pseudo put
Questions have previously been asked regarding which features are reversible with treatment:
Reversible complications Irreversible complications Cardiomyopathy Skin pigmentation Liver cirrhosis** Diabetes mellitus Hypogonadotrophic hypogonadism Arthropathy
Typical iron study profile in patient with haemochromatosis
transferrin saturation > 55% in men or > 50% in women
raised ferritin (e.g. > 500 ug/l) and iron
low TIBC
How can NAFLD be identified and how id the fibrosis staged?
Who is an risk?
All overweight/obese individuals (50% of population)
Older sedentary individuals
Type 2 diabetics/metabolic syndrome
Often goes undiagnosed as is it frequently asymptomatic and raised liver enzymes frequently ignored
How are patients with NAFLD typically identified?
Raised liver enzymes
Imaging evidence of steatosis
Present with imaging evidence of cirrhosis/liver cancer (too late!)
dIAGNOSIS
Raised ALT and/or GGT and evidence of steatosis on imaging
Imaging evidence of steatosis
Raised ALT and/or GGT and evidence of insulin resistance / central obesity / metabolic risk factors
No history of excess alcohol (<14/21 units/week)
No known pre-existing liver disease
No hepatotoxic drugs
Negative blood screen for other liver diseases (viral, autoimmune etc)
Liver biopsy may be required if there is diagnostic uncertainty
xRaised IgA in 46%
Raised ferritin with normal transferrin saturation in 33%
Staging for fibrosis FIB-4 score NAFLD fibrosis score ELF test Fibrotest ProC3
Transient elastography
Acoustic force radiation imaging (ARFI)
MR elastography
Generally tests are reasonably good at differentiating patients in to no/mild fibrosis
or advanced fibrosis/cirrhosis, but inaccurate in providing an exact fibrosis stage
How can NAFLD be managed?
General Lifestyle intervention (aim to lose >10% bodyweight) Specialist diet/exercise advice Weight loss adjuncts (orlistat) Modify cardiovascular risk Bariatric surgery (if meet criteria)
F0-F1
As above
Fibrosis reassessment every 3 years
F2-F3 Non-diabetic Vitamin E Clinical trial Diabetic Regimen including GLP-1 or Pioglitazone or empagliflozin Clinical trial
Cirrhosis Surveillance for HCC Variceal screening Bone density assessment Clinical trial
What follow up is usually given to a patient with Cirrhosis and decompensation?
Suggested medical follow up:
- Hepatocellular carcinoma: screening ultrasound and AFP every 6 months
- Variceal Haemorrhage: OGD at diagnosis of cirrhosis and every 2 years
- Beta-blocker (non-cardio-selective; carvedilol or propranol) as primary prevention of bleedingrebleed
- Viral Superinfection: Immunise for HAV and HBV (although this patient has already been exposed to HBV therefore would not require additional vaccination)
- Osteoporosis: Screen & treat
- Ascites & SBP: Monitor regularly for evidence of ascites & treat
- Vitamin deficiencies: Treat (Vit B Co-strong & Thiamine)
- Ongoing review with addiction services to help maintain abstinence from alcohol and illicit drugs.
What Scoring systems can be used to determine the severity of liver Cirrhosis?
For many years the Child-Pugh classification was used to classify the severity of liver cirrhosis. However, in recent years the Model for End-Stage Liver Disease (MELD) has been increasingly used, particularly patient’s who are on a liver transplant waiting list
Child-Pugh classification
Score 1 2 3 Bilirubin (µmol/l) <34 34-50 >50 Albumin (g/l) >35 28-35 <28 Prothrombin time, prolonged by (s) <4 4-6 >6 Encephalopathy none mild marked Ascites none mild marked
Summation of the scores allows the severity to be graded either A, B or C:
< 7 = A
7-9 = B
> 9 = C
MELD
Uses a combination of a patient’s bilirubin, creatinine, and the international normalized ratio (INR) to predict survival. A formula is used to calculate the score:
MELD = 3.78×ln[serum bilirubin (mg/dL)] + 11.2×ln[INR] + 9.57×ln[serum creatinine (mg/dL)] + 6.43
The 3-month mortality based on MELD scores: 40 or more: 71.3% mortality 30 - 39: 52.6% mortality 20 - 29: 19.6% mortality 10 - 19: 6.0% mortality < 9: 1.9% mortality
What are the indications for liver transplant in the UK?
Chronic liver failure UKELD ≥ 49 (Specific variant syndromes) Hepatocellular carcinoma multiple: up to 5 tumours ≤ 3cm single: up to 5cm (or 7cm if stable) (Acute liver failure)
What scoring systems are used in Alcoholic hepatitis?
Several models are available to determine the severity of alcoholic hepatitis.
The Maddrey discriminant function (DF), Model for End-stage Liver Disease (MELD) and Glasgow alcoholic hepatitis score (GAH) can all be used to assess the severity of alcoholic hepatitis. These scores are predominantly based on laboratory parameters.
Determining severity of alcoholic hepatitis is important to highlight patients with poor short-term survival and those who would benefit from pharmacological intervention.
Maddrey discriminant function
The DF score has been traditionally use to assess the severity of alcoholic hepatitis. It is based on serum bilirubin and prothrombin time.
DF = (4.6 x [prothrombin time (sec) - control prothrombin time (sec)]) + (serum bilirubin/17.1)
Serum bilirubin (umol/L)
Severe alcoholic hepatitis is defined as a DF score ≥ 32. The 28 day (one month) mortality among patients with a DF ≥32 ranges from 25-45%. Patients with a score < 32 have mild-to-moderate alcoholic hepatitis, which has a <10% mortality at 1-3 months.
Glasgow alcoholic hepatitis score
The GAH is a newer scoring system, which also predicts mortality among patients with alcoholic hepatitis. It is a slightly more complex score based on age, white blood cell count, urea, bilirubin and prothrombin time.
A score ≥ 9 is consistent with severe alcoholic hepatitis and associated with a poor 28-day and 84-day survival (46% and 40%, respectively).
What are the causes of an Upper Gi bleed?
Oesophagus
Oesophagitis Varices Malignancy Gastro-oesophageal reflux disease (GORD) Mallory-Weiss tear Stomach
Peptic ulcer disease Mallory-Weiss tear Gastric varices Gastritis Malignancy Duodenum
Peptic ulcer disease Diverticulum Aortoduodenal fistula Duodenitis Other
There are many other causes of upper GI bleeding though they are relatively less common.
Swallowed blood
Bleeding disorders
Dieulafoy’s lesion
Aortoenteric fistula
Hereditary haemorrhagic telangiectasia (Osler-Weber-Rendu syndrome)
Gastric antral vascular ectasia (GAVE, watermelon stomach)
What are the risk factors and features of an upper Gi bleed?
Risk factors Several risk factors increase the likelihood of a patient developing an UGIB. NSAIDs Anticoagulants Alcohol abuse Chronic liver disease Chronic kidney disease Advancing age Previous PUD or H. pylori infection NSAID-use
NSAIDs inhibit the synthesis of prostaglandins, which are gastroprotective.
Prostaglandins work by inhibiting enterochromaffin-like cells, which are involved in the secretion of histamine. Histamine stimulates parietal cells to secrete hydrochloric acid. Therefore, inhibition of prostaglandins leads to excessive HCl secretion and damage to the underlying mucosa.
Clinical features
The two characteristic clinical findings of UGIB are haematemesis and melaena.
Haematemesis refers to vomiting blood. Haematemesis may present with bright red bleeding or as ‘coffee-ground’ vomitus.
Melaena is the passage of ‘black, tarry stool’, which has an offensive odour. The colour is due to partly digested blood.
Symptoms
Haematemesis Dizziness Syncope Weakness Abdominal pain Dyspepsia Heartburn Melaena Haematochezia (passage of fresh blood per rectum) Weight loss Signs
Dehydration Pallor Confusion Tachycardia and hypotension Abdominal tenderness Melaena Haematochezia (10-15% of patients with acute, severe haematochezia have an UGIB) Stigmata of liver disease (e.g. spider naevi, ascites, hepatomegaly) Telangiectasia
What is the main investigation done in upper gi
bleed and what scoring system is used?
Upper GI endoscopy is the main diagnostic test. It should be completed immediately in any unstable patient following initial resuscitation, or within 24 hours in all other patients.
arly risk stratification helps identify high-risk patients & need for prompt intervention. Two scoring systems are used in patients presenting with UGIB.
UGIB scoring systems
Blatchford score
The Blatchford score takes into account a number of different clinical findings, biochemical parameters and past medical history. NICE recommends it is used during the primary assessment, followed by the Rockall score post-endoscopy.
Similar to the Rockall score, a score of 0 on the Blatchford score is associated with a low risk of mortality and patients can be considered for early discharge and non-admission.
Rockall scoring
The Rockall score is comprised of both a pre- and post-endoscopy score that can be added together to give an overall value.
The pre-endoscopy score is composed of three parts:
Age (0-2)
Shock (0-2)
Co-morbidity (0-3)
Patients with a score of 0 are at low risk of re-bleeding and death. This group of patients (approx. 15%) may be discharged early or not admitted.
The post-endoscopy score is composed of two sections:
Diagnosis (0-2)
Bleeding (0, 2)
This score can be remembered using the mnemonic ABCDE:
Age Blood pressure (and heart rate) Comorbidity Diagnosis Endoscopic findings
How can an Upper Gi bleed be managed?
All patients presenting with an UGIB should initially be resuscitated with respects to airway (A), breathing (B) and circulation (C).
Resuscitation
Airway Patent and protected Breathing Saturations Respiratory rate Breath sounds Circulation Blood pressure & heart rate ECG Establish IV access (two wide-bore cannula) Take blood (e.g. FBC, U&Es, clotting, LFTs, cross match) IV fluid if appropriate (0.9% normal saline) Consider blood products Endoscopy
Following resuscitation, unstable patients should be transferred for an immediate endoscopy. It is recommended that all other patients have endoscopy within 24 hours of admission.
Management can then be divided according to ‘non-variceal’ or ‘variceal’ bleeding.
Non-variceal bleeding
The most common cause of non-variceal upper GI bleeding is peptic ulcer disease. The need for intervention depends on the characterisation of the ulcer, which can be classified using the Forrest classification (beyond the scope of these notes). Management below focuses mainly on that of peptic ulcer disease. Alternative pathologies may be treated slightly differently (e.g. argon photocoagulation for angiodysplasia).
A number of techniques can be employed at the time of endoscopy to treat non-variceal causes of UGIB. In general, dual therapy should be given (i.e. adrenaline plus another modality)
Mechanical (e.g. clips) with adrenaline
Thermal coagulation with adrenaline
Proton pump inhibitor therapy should be reserved for patients with a non-variceal UGIB with evidence of recent haemorrhage during endoscopy.
A repeat endoscopy should be completed in patients who re-bleed, or are suspected to be high-risk of re-bleeding. Unstable patients who re-bleed post-endoscopy should be offered radiological (e.g. embolisation) or surgical intervention.
Variceal bleeding
Pharmacological intervention
Terlipressin (IV injection) Analogue of vasopressin (ADH) Causes splanchnic vasoconstriction This reduces portal pressures Prophylactic antibiotic therapy Reduces the risk of spontaneous bacterial peritonitis Endoscopic intervention
Variceal band ligation (VBL)
Completed acutely. Patients then need to undergo variceal banding programme every 2-4 weeks until varices have gone.
Endoscopic sclerotherapy
Alternative option to VBL that involves injection of a sclerosing agent.
Failed intervention
Patients may re-bleed despite endoscopic therapy. An initial re-attempt of variceal band ligation may be appropriate. If these attempts fail, further options include:
Sengstaken-blakemore tube:
Bridging therapy, at risk of oesophageal necrosis if left > 24 hours.
Oesophageal stent:
Alterantive to Sengstaken-blakemore tube.
Transjugular intrahepatic portosystemic shunt (TIPS) procedure:
Interventional radiological procedure to create a shunt between portal and systemic venous circulation to reduce portal pressure.
A definitive treatment in appropriately selected patients.
What is TIPPS and what is a complication?
HE
What are the causes of Hypertension?
-
Renal disorders are the most common cause of secondary hypertension. They include:
- Chronic pyelonephritis
- Diabetic nephropathy
- Glomerulonephritis
- Polycystic kidney disease
- Obstructive uropathy
- Renal cell carcinoma
-
Other causes ofsecondary hypertension are:
-
Vascular disorders, including:
- Coarctation of the aorta— usually results in upper-limb hypertension. There can be a significant difference in blood pressure between the left and right arms. Other signs include absent or weak femoral pulses, radio-femoral delay, palpable collateral blood vessels in the back muscles, and a suprasternal murmur radiating through to the back.
- Renal artery stenosis— suspect this if the person has peripheral vascular disease and an abdominal bruit, or if blood pressure is resistant to treatment.
-
Endocrine disorders, including:
- Primary hyperaldosteronism— probably the most common curable cause of hypertension. People usually present with hypokalaemia, alkalosis (elevated bicarbonate level), and plasma sodium level greater than 140mmol/L, or a larger than expected decrease in serum potassium when using a low-dose thiazide-type diuretic. The symptoms may be non-specific, but rarely it may present with tetany, muscle weakness, nocturia, or polyuria. Treatment with a calcium-channel blocker can mask the features of primary hyperaldosteronism. After identification of a possible adrenal adenoma on CT scan or MRI (magnetic resonance imaging), tertiary referral is required for confirmation of unilateral aldosterone excess and possible laparoscopic adrenalectomy.
- Phaeochromocytoma— people can present with intermittently high or labile blood pressure, or postural hypotension, headaches, sweating attacks, palpitations, or unexplained fever and abdominal pains. Alternatively, it can be asymptomatic. It is the rarest but most important cause of hypertension to diagnosebecause malignant transformation or catastrophic haemorrhage from the tumour can be fatal.
- Cushing’s syndrome— suspect this when clinical features are present (for exampletruncal obesity and striae). It rarely presents as hypertension alone.
- Acromegaly— suspect this if clinical features are present (for exampleenlargement of hands and feet, facial changes, sweating).
- Hypothyroidism — hypertension may result from altered levels of renin, angiotensin, and aldosterone, and is associated with an increased diastolic blood pressure. Clinical features may include fatigue, weight gain, dry skin and hair loss, constipation, and muscle weakness. See the CKS topic onHypothyroidismfor more information.
- Hyperthyroidism — increased systolic blood pressure may result. Clinical features may include tremor, anxiety, sweating, weight loss, diarrhoea, and heat intolerance. See the CKS topic onHyperthyroidismfor more information.
- **
- Connective tissue disorders (scleroderma, systemic lupus erythematosus, polyarteritis nodosa).
- Retroperitoneal fibrosis.
- Obstructive sleep apnoea. See the CKS topic onObstructive sleep apnoea syndromefor more information.
-
Vascular disorders, including:
What medication can causes hypertension?
Drugs and other substances, including:**
- Alcohol— misuse of alcohol may be the most common individual secondary cause of hypertension. Features include variable hypertension that is resistant to commonly used drugs and that disappears within a week or two of complete abstinence.
- Ciclosporin.
- Cocaine and other substances of abuse.
- Combined oral contraceptive.
- Corticosteroids.
- Erythropoietin.
- Leflunomide.
- Liquorice— present in some herbal medicines.
- Nonsteroidal anti-inflammatory drugs.
- Sympathomimetics— may be found in over-the-counter cough and cold remedies (for example ephedrine andphenylpropanolamine).
- Venlafaxine.
- **Other conditions, including:**
How does Hypertensive retinopathy present?
Hypertension may cause progressive retinal microvascular changes.
These changes have been classified by the Keith-Wagener Barker (KWB) grades:
Grade 1: Generalised arteriolar narrowing (silver wiring).
Grade 2: Focal narrowing and arteriovenous nipping.
Grade 3: Retinal haemorrhages, cotton wool spots (retinal nerve fibre layer micro-infarcts leading to exudation of axoplasmic materials).
Grade 4: Papilloedema
Grade may indicate malignant hypertension requiring admission and immediate management. Recently there has been a move away from the KWB grades with a new three stage system proposed.
How can Hypertensive emergencies be managed?
Hypertensive emergencies occur when high BP results in acute end-organ damage.
The term malignant (or accelerated) hypertension is typically reserved for when papilloedema is present and is defined by NICE as:
A BP >180/120 with signs of papilloedema and/or retinal haemorrhage.
It is a severe condition resulting in neurological, renal and cardiac damage, requiring admission and immediate management.
Treatment attempts to reduce BP over 24-48hrs. This is to prevent hypoperfusion. Changes may have occurred to autoregulatory mechanisms of blood pressure control. Therefore, a rapid reduction in blood pressure, even to normal levels, may result in profound organ hypoperfusion.
Therapies include:
IV Nitroprusside (a nitric oxide releasing drug), labetalol and glyceryl trinitrate infusions are options. Phentolamine (alpha-adrenergic antagonist) also used in phaeochromocytoma crisis.
What are the blood pressure targets for different populations?
Patients < 80 years: clinic BP < 140/90 mmHg / ABPM < 135/85 mmHg
Patients ≥ 80 years: clinic BP < 150/90 mmHg / ABPM < 145/85 mmHg
Those with renal disease and proteinuria or diabetes should target a BP of < 130/80 mmHg.
How can hypertension complications be managed?Who is treated?
Management of hypertension is based upon NICE guidelines.
Modifiable risk factors
Lifestyle modification & patient education are important in treating hypertension.
Offer advice that targets the patient’s modifiable risk factors.
Discourage excessive caffeine and alcohol, if appropriate offer smoking cessation advice.
Consider the need for anti-platelets or a statin.
Whom to treat
If clinic BP < 140/90 mmHg or ABPM < 135/85 mmHg, check BP at least every 5 years or more often if clinic BP close to 140/90 mmHg. If evidence of end-organ damage, consider other causes.
Antihypertensive drug therapy is initiated in patients:
Aged < 80 years with stage 1 hypertension and with one of the following; end organ damage, cardiovascular disease, renal disease, diabetes or 10-year cardiovascular risk ≥10%.
of any age with stage 2 hypertension
of any age with stage 3 hypertension (consider immediate treatment)
Consider treatment in patients > 80 years old with stage 1 hypertension if clinic BP is > 150/90 mmHg. However, take into account frailty and co-morbidities. Patients < 60 years with stage 1 hypertension can be considered for antihypertensive therapy even if the 10-year cardiovascular risk < 10%.
Specialist assessment
Patients with stage 3 hypertension (≥ 180/120 mmHg) should be referred for same-day specialist assessment if any features of accelerated hypertension are identified:
New onset confusion
Chest pain
Signs of heart failure (e.g. shortness of breath, fluid overload)
Acute kidney injury
Papilloedema
Retinal haemorrhage
In addition, any patient with suspected phaeochromocytoma needs same day assessment. If none of these features are present, patients should be urgently assessed for end-organ damage. If present, treatment should be considered immediately before ABPM/HBPM. If absent, blood pressure should be reviewed within 7 days in clinic.
Any patient aged < 40 years should be considered for specialist assessment to exclude a secondary cause of hypertension.
Name 5 side effects of each hypertensive drugs?
ACE inhibitors- Cough
Hyperkalaemia,Angioedema
Bendroflumethiazide- Gout
Hypokalaemia
Hyponatraemia
Impaired glucose tolerance
Calcium channel blockers
Headache
Flushing
Ankle oedema
Beta-blockers
Bronchospasm (especially in asthmatics)
Fatigue
Cold peripheries
Doxazosin
Postural hypotension
How to check for true postural hypotension
Orthostatic (postural) hypotension is an excessive fall in blood pressure (BP) when an upright position is assumed. The consensus definition is a drop of>20 mm Hg systolic, 10 mm Hg diastolic, or both. Symptoms of faintness, light-headedness, dizziness, confusion, or blurred vision occur within seconds to a few minutes of standing and resolve rapidly on lying down. Some patients experience falls,syncope, or even generalizedseizures. Exercise or a heavy meal may exacerbate symptoms. Most other associated symptoms and signs relate to the cause.
What medication can cause postural hypotension?
Antipyschotic
Antidepressants
Anti hypertension-ACEI,beta blocker
leva dopa
What is Phaecytochromia?How is to investigated and managed?
Phaeochromocytoma is a rare catecholamine secreting tumour. About 10% are familial and may be associated with MEN type II, neurofibromatosis and von Hippel-Lindau syndrome
Basics
bilateral in 10%
malignant in 10%
extra-adrenal in 10% (most common site = organ of Zuckerkandl, adjacent to the bifurcation of the aorta)
Features are typically episodic hypertension (around 90% of cases, may be sustained) headaches palpitations sweating anxiety
Tests
24 hr urinary collection of metanephrines (sensitivity 97%*)
this has replaced a 24 hr urinary collection of catecholamines (sensitivity 86%)
Surgery is the definitive management. The patient must first however be stabilized with medical management:
alpha-blocker (e.g. phenoxybenzamine), given before a
beta-blocker (e.g. propranolol)
How can AKI be diagnosed?
AKI may be classified by a number of systems including RIFLE and KDIGO.
A number of different staging systems have been proposed to help grade the severity of AKI including the ‘RIFLE’ criteria, ‘AKIN’ criteria and more recently the ‘Kidney Disease: Improving Global Outcomes’ (KDIGO) criteria.
Based on the KDIGO criteria, an AKI is defined by one of the following parameters:
An increase in serum creatinine by ≥ 26.5 micromol/L within 48 hours
An increase in serum creatinine to ≥ 1.5 times baseline within 7 days
Urine output < 0.5 mL/kg/hr for six hours
What are features of history and clinical examination that may indicate AKI?
Risk factors There are a number of risk factors that increase the likelihood of developing an AKI during hospital admission. Age (> 65 years old) History of AKI CKD Urological history (e.g. stones) Cardiac failure Diabetes mellitus Sepsis Hypovolaemia Nephrotoxic drug use Contrast agents
Patients usually present with clinical features of hypovolaemia & dehydration. Reduced capillary refill time Dry mucous membranes Reduced skin turgor Thirst Dizziness Reduced urine output Orthostatic hypotension It is important to consider features associated with fluid loss including excessive sweating, vomiting, diarrhoea and polyuria. In elderly patients, there may also be evidence of confusion.
In patients with renal hypoperfusion in the context of hypervolaemia (e.g. cardiac failure), it is important to assess for fluid overload.
Ankle swelling Orthopnoea Paroxysmal nocturnal dyspnoea Dyspnoea Raised JVP Ascites Intrinsic renal
The clinical presentation of intrinsic renal AKI is dependent on the specific aetiology.
Patients with ATN will demonstrate features consistent with the underlying aetiology. Those with intrinsic glomerular pathology may present with features of nephritic syndrome (e.g. haematuria, proteinuria, oliguria and hypertension) or nephrotic syndrome (e.g. heavy proteinuria, hypoalbuminaemia and oedema).
Patients with a tubulointerstitial disease (e.g. acute interstitial nephritis) may complain of arthralgia, rashes and fever. Eosinophilia is frequently seen.
Post-renal
The clinical features of post-renal AKI depend on the site, chronicity and laterality (unilateral or bilateral) of the obstruction.
Patients with urinary stones may present with classical loin-to-groin pain, haematuria, nausea and vomiting. Those with prostatic problems may have lower urinary tract symptoms (e.g. dysuria, frequency, terminal dribbling, hesitancy). Obstruction at the bladder neck might be associated with a palpable bladder and a tender suprapubic area.
How is AKI managed and What is RENAL DRS 26?
anagement
The management of an AKI should involve regular assessment and monitoring, controlling volume dysregulation and correcting electrolyte abnormalities and metabolic acidosis.
Principles of management
Management is guided by the underlying cause. Here we will discuss the general principles of management that can be applied to most cases of AKI.
Patients can be staged according to the KDIGO criteria. It is suggested that patients who have stage 3 AKI or a suspected diagnosis that may require specialist intervention (e.g. glomerulonephritis, systemic vasculitis), be discussed with a nephrologist within 48 hours of detection. Patients with post-renal AKI may require discussion with a urologist.
Regular assessment and monitoring
Regular assessment of the patients’ fluid status should be completed including monitoring their urine output, which may require a urinary catheter and daily weights.
A baseline creatinine should be recorded and serial U&Es taken daily, increased to twice daily in more severe cases.
Nephrotoxic drugs should be stopped (e.g. ACEi, NSAIDs, spironolactone) and regular prescriptions should be altered to reflect the change in creatinine clearance.
Volume dysregulation
If patients are hypovolaemic then intravenous fluids should be prescribed. The amount and type of fluids will depend on the clinical status of the patient.
If the patient is hypervolaemic they may require fluid restriction +/- the use of diuretics. Diuretics (e.g. furosemide) should be used carefully in renal impairment as they can be nephrotoxic.
Electrolyte abnormalities
Severe hyperkalaemia, variably defined as >6.5 or 7 mmol/L, is a medical emergency.
The management of hyperkalaemia is critical to avoid potential life-threatening arrhythmias. It involves:
Protection of the myocardium: 10ml of 10% calcium gluconate.
Reduce extracellular potassium: aim is to drive potassium into the intracellular compartment. Insulin (e.g 10 units ACTRAPID in 100ml 20% dextrose) and beta agonists (e.g. 2.5mg nebulised salbutamol) are given.
Additional: stop or adjust potassium-sparing or potassium-containing medications. Resins can reduce potassium absorption but these take hours/days to have effect.
Other electrolyte problems include hypocalcaemia and hyperphosphataemia.
Metabolic acidosis
The handling of acid-base is impaired in the setting of AKI due to a reduction in the GFR. This can results in a metabolic acidosis. Depending on the severity of acidosis and associated clinical state, choices for management involve the use of sodium bicarbonate or dialysis.
Complications
The major complications that can occur in association with AKI include hyperkalaemia, fluid overload, metabolic acidosis and uraemia.
The development of uraemic complications (e.g. encephalopathy, pericarditis), hyperkalaemia, fluid overload or metabolic acidosis that are refractory to medical therapy warrant urgent dialysis.
A useful mnemonic for assessment and management of any patient presenting with an acute kidney injury.
RENAL DRS 26 mnemonic
R-record baseline creatinine E-Exclude obstruction N-Stop nephrotoxic drugs A-Assess fluid status L-losses and catheterisation D-Dipstick R-Review meds S-Renal screen 26-Greather than 26 rise in creatinine
