Primary care - GI & Renal Flashcards
What is the pathophysiology of type 1 diabetes?
Autoimmune destruction of Beta cells in Islets of Langerhans of pancreas
leading to lack of production of insulin
Glucose cannot be taken up from blood or
converted to glycogen for storage
What is the pathophysiology of type 2 diabetes?
Beta cells remain intact but may secrete less insulin
Other cells also become
insensitive to insulin (insulin resistance)
What genes are responsible for type 1 diabetes?
HLA-DR3
HLA-DR4
How does type 1 diabetes present?
Rapid onset of clinical triad over days/weeks
- Polyuria
- Polydipsia
- Weight loss
What are some long-term complications of diabetes?
Retinopathy Neuropathy Nephropathy Erectile dysfunction Vascular disease - main cause of death
How does diabetic ketoacidosis present? What would you see on bloods?
Nausea + vomiting
Severe confusion
Dehydrated - dry mucus membranes and reduced skin turgor
Ketotic breath
Kaussmal breathing - deep sighing breaths to try breathe off CO2
Generalised GCS
On bloods, would see:
- high creatinine, sodium, potassium and phosphate
- low bicarb
- high glucose
- low pH
What is the criteria for diagnosis of diabetes?
One abnormal plasma glucose in the presence of symptoms
Random blood glucose >11.1mmol/l
Fasting blood glucose >7mmol/l
HbA1c > 47mmol/L
If asymptomatic: 2 fasting venous glucose samples in abnormal range OR OGTT 2hr value >11.1mmol/l
What is the gold standard test for diabetes?
Glucose tolerance test
Ask patient to fast overnight, then give 75g of glucose. Check plasma glucose after 2 hrs.
• ≥11.1mmol/L = diabetic
• ≥7.8 and <11.1mmol/L = impaired glucose tolerance
• <7.8mmol/L = non-diabetic
What is the pharmacological management of T2DM?
STEP 1 = Metformin 500mg BD after food
If HbA1c >58 16 weeks later add…
STEP 2 = Metformin + sulphonylurea (gliclazide 40mg OD)
If at HbA1c >57 at 6 months consider…
STEP 3 = Insulin, Glitazone, Meglitinides, Incretin mimetics, Acarbose
What class of drug is metformin in?
Biguanides
How does metformin work?
Reduces rate of gluconeogenesis
Increases insulin sensitivity to increase uptake of glucose by cells but doesn’t affect insulin output
What are some side effects of metformin?
GI upset
Weight loss
When is metformin contraindicated?
Renal dysfunction
What kind of drug is gliclazide and what does it do?
Sulphonylurea
It stimulates pancreatic insulin secretion - can cause hypoglycaemia
Can cause weight gain because insulin is an anabolic hormone
How do glitazones work?
Increase insulin secretion and sensitivity to insulin
What are side effects of glitazones?
When are they contraindicated?
Fluid-retention - increased risk of HF
Anaemia
Osteoporosis
C/I in cardiovascular disease
What does acarbose do?
Decreases breakdown of starch to sugar
What are the side effects of acarbose?
Severe flatulence
Abdominal distention
Diarrhoea
Where in the colon is diverticular disease most common?
Sigmoid colon
What are the risk factors for diverticular disease?
Low fibre diet Smoking Chronic NSAID use Age Obesity
How does diverticulitis present?
Altered bowel habit Abdominal pain - usually left-sided and colicky Nausea Flatulence Symptoms improve on defaecation Febrile if acute
How does a perforated diverticulum present?
Ileus
Peritonitis
Shock
Requires urgent surgical assessment
What is the treatment of diverticulitis?
Abx - metronidazole
Fluids
Analgesia - avoid opioids
Difference between Crohn’s and ulcerative colitis: area affected
Crohns:
- any part of GI tract
- most commonly terminal ileum
- transmural
- skip lesions present
UC:
- colon
- distal regions worse affected
- lesions are constant
Difference between Crohn’s and ulcerative colitis: presentation
Crohn’s:
- pain worse after eating
- normal bowel frequency
- malnourished due to decreased absorption - vitamin b12 + iron deficiencies
- mass in right iliac fossa
- anal fistula/abscess/stricture
UC:
- diarrhoea with blood + mucus
- pain worse in morning
- tenesmus - most commonly affects rectum (proctitis)
What is protective for UC?
smoking
appendectomy
What extra-intestinal symptoms are present in IBD?
Both:
- clubbing
- Pyoderma gangrenosum (but more commonly Crohn’s)
- Episcleritis
- Anterior uveitis
Crohn’s:
- Aphthous ulcers
- Erythema nodosum (also caused by strep infection, sarcoidosis, sulfonamides, TB)
- Ankylosing spondylitis
UC:
- Clubbing
- Arthropathy
- Primary sclerosing cholangitis
What is an acute complication of ulcerative colitis?
Toxic megacolon = fulminant colitis
- Acute colonic dilatation so transverse colon is > 6cm diameter
- Extension of inflammation beyond mucosa
- Loss of contractility leads to accumulation of gas and fluid
- Risk of perforation
What investigations are done for IBD?
- Colonoscopy + biopsy
- MRI to detect fistulae
- FBC, CRP, B12, folate
- Faecal calprotectin tests for GI inflammation
Difference between Crohn’s and ulcerative colitis: histopathology
Crohn’s:
- Transmural granulomatous inflammation -> fibrosis + stenosis -> fistulae + abscesses
- Cobblestone appearance
- thickened bowel wall
UC:
- Crypt abscesses = defining lesion
- Micro ulcers
- Inflammatory polyps
- Inflammation is NOT transmural
- thinned bowel wall
What is the treatment for Crohn’s?
Smoking cessation
Prednisolone 40mg per day for 1 week then taper by 5mg each week for 7 weeks
Immunosuppressants if recurrent attacks e.g. azathioprine, infliximab
50% require surgery
What is the treatment for ulcerative colitis?
Steroids to induce remission
5-ASA e.g. mesalazine OD to maintain
Surgery if failing to respond to medical therapy
When is mesalazine contraindicated?
Aspirin hypersensitivity
What drugs does mesalazine interact with?
PPIs - they increase the pH so the gastric protection is broken down in the stomach
Lactulose - decreases the pH of stools so it prevents release in the colon
What genes are linked to coeliac disease?
HLA-DQ2 (95%)
HLA-DQ8
What symptoms are most common in coeliac disease?
Weight loss
Diarrhoea
Anaemia - iron or b12 deficiency
What skin condition is related to coeliac disease?
Dermatitis herpetiformis
What is seen on histology of coeliac disease?
Villous atrophy
Crypt hyperplasia
WBC infiltration
How do you diagnose coeliac disease?
All tests must be done whilst eating a gluten-containing diet
- Total IgA and IgA tissue transglutaminase = 1st choice
- If the first test was only weakly positive, test IgA EMA (endomysial antibodies)
- If IgA is deficient, test IgG
What happens to the liver in chronic liver disease?
Liver is replaced by fibrotic tissue and regenerating nodules of hepatocytes
80% of liver parenchyma is destroyed before symptoms arise
What are some signs of chronic liver disease?
- Leukonychia
- Palmar erythema
- Dupytrens contracture
- Spider naevi
- Gynaecomastia
- Loss of axillary hair
- Parotid swelling
- Caput medusa
What are some infectious causes of chronic liver disease?
Hepatitis B Hepatitis C CMV Yellow fever Leptospirosis
What drugs can cause chronic liver disease?
Methotrexate Paracetamol overdose Amiodarone Sodium valproate Nitrofurantoin Isoniazid
What conditions can cause chronic liver disease?
Primary biliary cholangitis Primary sclerosing cholangitis Haemochromatosis Alpha1-antitrypsin deficiency Wilson's disease (Chr13 - disorder of hepatic copper deposition) Autoimmune hepatitis
What would blood results show in chronic liver failure?
Clotting
- High INR
- Prolonged PT
FBC
- Thrombocytopenia (low platelets)
LFTs
- high ALT (a lot more specific)
- high AST
- high ALP
- high bilirubin
U&Es
- high ammonia (the liver converts ammonia to glutamine which can be excreted as urea by the kidneys)
Define chronic kidney disease
Abnormal kidney structure or function present for >3 months with implications for health
What can cause chronic kidney disease?
VITAMIN CDE surgical sieve
Vascular - hypertension, renal artery stenosis, heart failure
Inflammatory - glomerulonephritis, pyelonephritis, interstitial nephritis
Autoimmune - SLE
Metabolic - diabetes, renal stones, urinary tract obstruction, hypercalcaemia
Neoplastic - renal cancer
Congenital - renal dysplasia, Alport syndrome, Fabry disease
Environment/endocrine - parathyroid disease, drugs, malnutrition
What are the most common causes of chronic kidney disease in the UK?
- Diabetes mellitus
- Glomerulonephritis
- Hypertension
When does CKD become symptomatic?
When eGFR<30 which is stage 4 CKD
What are some symptoms of CKD?
- Fluid overload: SOB, oedema, polyuria
- Anorexia, nausea, vomiting
- Pruritis
- Bone pain
- Insomnia
- Restless legs
What does FBC show in CKD?
Normochromic normocytic anaemia i.e. anaemia of chronic disease; due to decreased erythropoietin production
What do U&Es show in CKD?
- Low calcium, high phosphate (renal osteodystrophy)
- Low sodium, high potassium
- Low bicarb
- High urea, high creatinine
What imaging would you do in CKD? What would you see?
Ultrasound scan of kidneys for size, symmetry, anatomy, corticomedullary differentiation and to exlude obstruction
- Small kidneys (<9cm) except in amyloid, myeloma, diabetes
- Asymmetrical = renovascular disease
What is the gold standard investigation for CKD?
Isotopic eGFR
What further investigations should you consider for progressive CKD or AKI without recovery?
renal biopsy
How can you slow renal disease progression?
- Target BP < 140/90; in diabetes target is < 130/80
- ACE inhibitors
- Statins
- Antiplatelets e.g. aspirin
- Target HbA1C < 53mmol/mol
- Lifestyle advice: reduce salt intake, smoking cessation, exercise
What are some complications of CKD and how can they be managed?
Anaemia
- treat any iron, folate, b12 deficiencies
- give erythropoietic stimulating agent if Hb<11g/dL
Acidosis - sodium bicarbonate supplements if eGFR < 30
Oedema - high dose loop diuretics (can be combined with thiazide)
Renal osteodystrophy - vitamin D supplements
Restless legs/cramps
- iron deficiency may be cause
- sleep hygiene advice
- gabapentin
Which medications are nephrotoxic?
A DIAMOND + Li
Aminoglycosides
Diuretics (especially potassium sparing) Iodine contrasts/immunosuppressants Antihypertensives e.g. ACEi, ARB Metformin Opioids NSAIDs Digoxin
Lithium
What is the difference in pathophysiology of nephrotic and nephritic syndrome?
Nephrotic - increased permeability of podocytes in glomerular capillary membrane to plasma proteins»_space; hypoalbuminaemia
Nephritic - decreased membrane permeability due to inflammatory response
What causes nephritic syndrome?
Glomerulonephritis from acute post-streptococcal infection
How does nephrotic syndrome present?
NEPHROTIC
Na+ decreased (hyponatraemia) Albumin decreased (hypoalbuminaemia) Proteinuria Hyperlipidaemia Renal vein thrombosis Orbital oedema Thromboembolism Infection (loss of Ig in urine) Coagulability increase (due to loss of antithrombin II in urine)
Due to impaired excretion, what drugs should be avoided/dose reduced in CKD?
Digoxin
Aminoglycosides
Acyclovir
Opiates
What can cause a relatively low serum creatinine?
Low muscle mass:
- Being elderly due to wasting of muscles
- Female
- Amputees
What is the diagnostic criteria for DKA?
Random glucose > 11
Venous ketones > 3 or urinary ketones 2++
Venous pH < 7.3
Bicarb < 15
What is the management of DKA?
- First bag of fluid over 1 hour (sodium chloride not hartmanns), second bag over 2 hours, third bag over 2 hours and third bag over 4 hours
- Fixed rate insulin 0.1units/kg/hour
- Monitor potassium because at risk of hypokalaemia (insulin drives potassium into the cells)
What is the DKA equivalent for type 2 diabetes?
HHS = hyperosmotic hyperglycaemia state
What often precipitates HHS?
Underlying infection
How do you diagnose HHS?
- Hypovolaemia
- Hyperglycaemia > 30 mmol/L
- Without significant hyperketonaemia
- Without significant acidosis
- Osmolality > 320mosmol/kg (glucose + urea + 2xNa)
What is the management of HHS?
Mainstay treatment = fluid resuscitation
Consider IV insulin (half as much as in DKA so 0.05units/kg/hr
Prophylactic LMWH
What are the benefits of metformin?
- Protects the heart
- Weight neutral
- Doesn’t cause hypos
What injectable, other than insulin, can be used in type 2 DM?
GLP-1 agonist
- Reserved for particularly overweight people
- Delays gastric emptying
- Once daily injection
- Must prove 11mmol HbA1c reduction in 6 months
What diabetes drug reduces glucose reabsorption in kidney?
SGLT-2 inhibitors - cause you to wee out more glucose
What are the side effects of SGLT-2 inhibitors?
UTIs
Thrush
Weight loss
Slight increased risk of DKA with canagliflozin
