Weight loss Flashcards
LO: Define weight loss and identify whether intentional or unintentional
What is weight loss?
What does involuntary weight loss often indicate?
When is it regarded as a medical problem?
Weight loss = result of decreased energy intake or increased energy expenditure
Progressive involuntary weight loss often indicates a serious medical or psychiatric illness.
It is generally regarded as a medical problem when > 10% of a person’s body weight has been lost in 6 months or > 5% in the last month.
What three factors can contribute to weight loss?
What are the consequences of low body weight?
Factors contributing to weight loss:
1) insufficient nutrient intake/ poor appetite
2) increased energy requirements
3) decreased nutrient absorption
Consequences of weight loss:
- Poor immune response
- Poor wound healing
- Poor muscle strength
- Electrolyte/ fluid dysfunction
- Irregular menstruation
Define unintentional weight loss
Unintentional weight loss if often defined as weight loss of at least 5% of the patient’s usualy body weight that occurs within the preceding 6-12 months. It is not the expected consequence of treatement of a known illness.
What is cachexia?
Cachexia is a related syndrome to unintentional weight loss.
Cachexia - syndrome of weight loss characterised by decreased muscle mass in the presence of metabolic effects of underlying disease e.g. cancer or advanced heart failure.
Whilst all patients with cachexia have unintentional weight loss not all cachexia patients have sarcopenia
What is sarcopenia?
Sarcopenia is a geriatric syndrome of diminished muscle mass and function which may or may not be accompanied by unintentional weight loss.
LO: identify important epidemiological factors related to unintentional weight loss
- unintentional weight loss is present in 8% of elderly who seek care
- Increased incidence of mortality
- increased perioperative complications
- higher risk of depression
- higher risk of infection
LO: Understand the important factors when eliciting a history of weight loss which may help develop appropriate differential diagnoses
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HPC: quantify the weight loss, clarify whether intentional or unintentional
- how much weight loss over how much time?
- intentional or unintentional?
- Clothes no longer fitting?
- Appetite change?
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Age:
- Younger age –> psychiatric and GI conditions or cancers affecting young (lymphoma or leukaemia). Neurological –> MS/ALS and CF. GI –> coeliac disease often in younger patients
- older age –> CV or cancer. Neurological –> dementia and parkinsons disease.
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Systems review: symptoms related to aetiology
- change in bowel habit - steatorrhoea/ malaena/constipation/ diarrhoea/ increased frequency
- nausea or vomiting?
- pain
- fever
- night sweats
- muscle weakness
- bone pain
- increased thirst?
- fatigue?
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PMH:
- Cachexia related to chronic disease - CHF/Renal failure/ COPD
- CF: new onset or worsening GI malabsorption
- Coeliac disease –> non adherence to gluten free diet
- Bipolar disorder –> mania?
- Prior pancreatitis –> can lead to pancreatic insufficiency
- Hep B or C infection
- cancer screening?
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Drug history –> some medications can cause weight loss, any recreational drug use?
- Anti convulsants and antidepressants
- diabetes medication
- antibiotics
- cholinesterase inhibitors –> donepezil
- laxative/ diuretics or thyroid hormone misuse
- Psychiatric history --> anhedonia? early morning waking? diurnal mood variation? memory loss/ dementia
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Social history –>
- any weight loss related to alcohol dependency or smoking? (smoking suppresses appetite, alcohol linked to malnutrition -> wernickes encephalopathy related to lack of B1 thiamine, pernicious anaemia related to lack of B12 absorption)
- Homelife –> homelessness and lack of access to food
- Travel hx –> related to TB infection
- Family hx –> inherited conditions (CF) or malignancy?
Hx of weight loss:
Symptoms and related aetiology?
- 1) Degree of weight loss –> Cancer/ GI/ severe infection (HIV) have higher degree of weight loss
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2) systemic symptoms:
- weakness = common sx
- fever/ chills/ night sweats: infection (TB) or haematological malignancy, rheumatological conditions
- cachexia - in advanced chronic disease
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3) GI:
- dysphagia –> oesophageal CA
- abdominal pain –> GI cancer or peptic ulcer disease w aneamia. RUQ pain + jaundice in liver CA. Pancreatic CA pain is advanced stage. GI conditions: coeliac/IBD/exocrine pancreatic insuffiency
- post prandial pain –> peptic ulcer disease or mesenteric ischaemia
- heat burn –> GORD/ peptic ulcer disease
- diarrhoea –> GI conditions - coeliac / iBD/ exocrine pancreatic insuffiency. GI cancer carcinoid tumour (slow growing neuroendocrine tumour in GI tract). Infection
- Blood in stool –> IBD or lower GI malignancy
- Black tarry stool –> upper GI bleed
- oily floating stool -> malabsorption e.g. coeliac or exocrine pancreatic insuffiency
- Rectal bleeding: common in colorectal cancer
- Genitourinary: LUTS - prostate CA, especially if bone pain present. Lower pelvic pain - ovarian CA especially if abdominal bloating
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Endocrinology:
- fatigue/ palpitations/ anxiety/ heat intolerance = hyperthyroidims
- polyuria and polydipsia = diabetes, type 1 more commonly associated with weight loss than type 2
- fatigue, orthostatic hypotension and weakness - adrenal insuffiency
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Resp:
- haemptysis –> TB or lung CA
- cough –> TB or lung CA
LO: Describe clinical signs associated with weight loss and signs which may indicate its underlying cause
How should you examine weight loss (general) and what are some key clinical signs?
Examination of weight loss:
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General observations:
- temperature (fever?)- infection/ malignancy/ inflammatory condition
- RR / HR/ BP –> tachycardia hyperthyroidism
- mental status –> delerium/ altered mental status (electrolye imabalance? infection or endocrinopathy (hyperT), cognitive impairment in dementia.
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signs of malnutrition:
- cachexia?
-
clubbing -
- causes mnemonic = CLUBBING
- Cardiac - infective endocarditis/ cyanotic heart disease
- Lung - CF/ TB/ Pulm fibrosis/ bronchiectasis
- Ulcerative colitis
- Biliary cirrhosis
- Bronchiogenic carcinoma
- Idiopathic
- NOT COPD
- Gastrointestinal - malabsorption/ coeliac/ crohn/ cirrhosis
- koilonychia - iron deficiency anaemia (malnutrition/GI bleed/coeliac)
- chelitis/ stomatitis - vitamin deficiency or side effect of medication (HIV antiretroviral medications)
- Glossitis –> associated with B12 and thiamine deficiency (alcohol dependency), chrohns disease and smoking
- Pellegra - Niacin B3 deficiency = dermatitis with reddening and thickening of the skin on hands and face, also associated with diarrhoea (alcoholism)
What other examinations can be done in the investigation of weight loss?
Depending on patient hx and other signs:
- Systemic exam:
- Lymphadenopathy - malignancy or infection
- bone or joint pain - metastatic CA or rheumatological condition
- paraneoplastic syndrome - SCLC associated with variety of paraneoplastic conditions including hypercalcaemia, SIADH.
- Abdo exam: masses/ hepatomegaly/splenomegaly/ascites - malignancy alcoholism
- Genitourinary: masses - prostate/rectal/pelvic? (malignancy)
- CV: new murmur (infective endocarditis), decompensated HF sings - crackles, peripheral oedema, elevated JVP
- Resp: crackles (interstitial lung disease/ pneumonia), hyperinflation - COPD
- Dermatological:
- dermatitis hepatiformis - coeliac disease = itchy blisters and raised red skin lesions, commonly on elbows/knees/buttocks/ lower back and scalp.
- lesions - skin cancer
- janeway lesions/ oslers nodes - infective endocarditis
- rash - malar or discoid = SLE
- Breast exam - in M & W
- dental exam - poor dentition can decrease oral intake, also risk factor for infective endocarditis
Hx of weight loss:
What medications may be related to weight loss?
Drugs related to weight loss:
- Anorexia inducing drugs –> amphetamines (meth/speed), anticonvulsants/ benzodiazepines/ SSRI’s/ opiates/ metformin/ levodopa/ digoxin/ gold
- Dry mouth –> anticholinergics, antihistamines, loop diuretics
- Dysgeusia (distortion of sense of taste) and dysosmia (distortion of perception of smell) –> alcohol, Abx, chemo, iron, lithium, opiates, statins, TCA’s
- dysphagia –> bisphosphonates, chemo, corticosteroids, iron, NSAID
- nausea and vomiting –> abx, bisphosphonates, metformin, opiates, SSRI, statin, TCA’s
Aetiology of weight loss?
Weight loss can be due to:
1) decreased intake or poor appetite vs 2) normal appetite and intake but underlying disease.
Decreased intake or poor appetite:
- Organ failure –> Cardiac/ renal or lung
- Systemic infection e.g. TB or HIV
- Cancer –> lymphoma / leukaemia/ colorectal cancer
- GI inflammation - e.g. IBD
- Psychiatric illness –> dementia, depression or stressful life events
Normal appetite and intake: but decreased absorption or increased energy requirements
- Gastrointestinal –> malabsorption - coeliac or crohn’s
- Endocrine –> hyperthyroidism or diabetes
Related to both decreased intake or poor appetite + increased energy requirements/ decreased absorption = systemic inflammation (RA, SLE, vasculitis)
Other causes: drug related, alcoholism, respiratory disease, neurological disease, renal disease, chronic infection
What are some of the important differential diagnoses for weight loss?
VITAMIN D
Vascular - heart failure, renal failure
Inflammatory - IBD- crohn’s
Trauma
Autoimmune - SLE/Coeliac/IBD
Metabolic - hyperthryoidism, diabetes
Infective - HIV/ TB
Neoplastic - primary or secondary malignancy
Degenerative/ Drugs- dementia/depression/substance abuse/anorexia or bulimia/ drugs
LO: describe what bedside, clinical, lab and radiological investigations would be appropriate to investigate a patient with unexplained weight loss
What screening tool should be used in initial assement of a patient with weight loss?
- Bedside screening tool = MUST = Malnutrition universal screening tool
- 5 MUST steps:
- Step 1: BMI
- Step 2: % Unexplained weight loss score - 5-10% score 1, > 10% score 2
- Step 3: acute disease? –> is the patient acutely unwell or likely had no nutritional intake for > 5 days = score 2
- Step 4: stratify the overall risk of malnutrition –> score 0 = low risk, score 1 = medium risk, score 2 = high risk
- step 5: management guidelines depending on risk:
- low risk - repeat screeing
- medium - observe
- high - referral dietician, nutritional support team, onitor and review
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LO: describe what bedside, clinical, lab and radiological investigations would be appropriate to investigate a patient with unexplained weight loss
Bedside investigations:
- Urinalysis - urine dip / MSU
- Faecal occult blood - in patients with weightloss suspect GI malignancy
- nutritional assessment - MUST tool
Bloods:
- FBC - anaemia
- U&E
- LFT’s
- CRP/ plasma viscosity/ ESR - ESR or CRP = inflammation infection or malignancy
- adjusted calcium
- phosphate/ magnesium - part of investigation for refeeding syndrome
- Thyroid function
- Blood sugar/ HbA1C
Special bloods:
- Haematinics - folate, B12, ferritin
- Vitamin D levels
- Endomysial/ antiTTG antibodies
- HIV testing
Imaging:
CXR - mass on lung or evidence of other lung disease, mediastinal mass or lymphadenopathy
Abdominal USS - suspected malignancy
CT abdo/ pelvis- suspected malignancy
mammogram
Special tests:
- Upper GI +/- duodenal biopsy - patients with uninentional WL/anaemia/ upper abdo pain or dysphagia
- Colonoscopy / sigmoidoscopy - unintentional WL + anaemia/ heme positive stools/ gross rectal bleeding/ abdo pain or change in stool caliber
General vs specific testing for weight loss?
(basically revise all the investigations one more time :) )
Differentials for weight loss:
What are the malabsorptive conditions?
Malabsorptive conditions:
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Mucosal disease of the small bowel
- Coeliac disease
- small bowel infection - giardia, tripical sprue, whipple’s disese, intestinal TB, bacterial overgrowth
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Intraluminal disease
- Chronic pancreatitis
- Cystic fibrosis
- Pancreatic cancer
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Structural causes:
- Crohn’s disease
- post surgical
- Other –> carcinoid tumour, laxative abuse, hyperthyroidism
Malabsorptive disease: Coeliac disease
Pathophysiology?
- Coeliac disease is an autoimmune condition
- Alpha Gliadin is the antigen –> produced from gluten
- affects the proximal ileum –> distal ileum
- leads to subtotal vilous atrophy
- Loss of immune tolerance to gluten peptides from grains within wheat (Gliadin) /rye/barley and related grains
- peptide antigens are resistant to human proteases which allows them to persist intact in the small intestine lumen
- These peptides gain access to the lamina propria
- once in the intestinal submucosa these peptides trigger innate and adaptive immune activation
- Gluten peptides stimulate IL production by dendritic cells/ macrophages and intestinal epithelial cells which triggers intraepithelial lymphocytes –> leads to epithelial damage
- Gluten peptides are deamidated (have amide group removed) by enzyme tissue transglutaminase (tTG).
- This allows the peptide to bind to HLA peptides (Major histocompatability complexes) on antigen presenting cells and T helper cells which activates them
- Note almost all people with coeliac disease carry one of 2 major histocompatability complex class ii molecules (HLADQ2 or DQ8) (they are required to present the gluten peptides in a manner that activates antigen specific T cell response).
- T helper cells then leads to cell death and tissue remodelling with villous atrophy and crypt hyperplasia - induced by Cytotoxic T lymphocytes
- Th2 cells trigger plasma cell maturation and production of antigliadin and anti-tTG antibodies.
What investigations would you do to investigate coeliac disease?
- FBC and blood smear –> low Hb and microcytic RBC’s –> iron deficiency anaemia most common clinical presentation. Folate and rarely B12 deficiency may lead to macrocytic anaemia
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Serological testing:
- IgA-tTG - immunoglobulin A tissue transglutaminase - elevated.
- endomysial antibody EMA - elevated (alternative to anti-tTG)
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skin biopsy - in patients w dermatitis herpetiformis (granular deposits of IgA in dermal papillae)
- IgG DGP = deamidated gliadin peptide - elevated (test of choice in IgA defiency)
- Endoscopy - may see atrophy and scalloping of mucosal folds
- small bowel histology -Jejunal mucosal biopsy- villous atrophy, crypt hyperplasia, intraepithelial lymphocytes
Complications of coeliac disease?
- Non adherence to Gluten free diet can cause rare complication --> small intestinal T cell lymphoma!
- Iron deficiency anaemia
- Osteoporosis –> fractures
- Small bowel and oeosphageal carcinoma
Investigations of suspected oesophageal carcinoma?
- FBC/ U&E/s / LFT’s
- metabolic profile - electrolytes epspecially patients can become v dehydrated and hypokalaemic due to inability to swallow potassium rich saliva
- OGD = oesophagogastroduodenoscopy with biopsy
- first test in patients presenting with dysphagia, odynophagia or weight loss
- With cancer will show mucosal lesion, histology shows squamous carcinoma or adenocarcinoma.
- staging with CT or MRI/PET scan
Why do patients with malignancy present with weight loss?
- Obstruction of the GI tract - dysphagia - symptoms directly from cancer
- Indirect symptoms - other symptoms such as constipation/ nausea/ pain/ resp distress/ fatigue/ electrolyte imbalance causing nausea/ psychiatric disorder
- Chemotherapy induced- N&V, mouth and throat problems, radiotherapy
Pathophysiology of pernicious anemia?
Cobalamin (B12) is freed from meat by acidic digestion, it then binds R factors in competition with intrinsic factor.
Cobalamin is free from R factors in the duodenum by proteolytic digestion by pancreatic enzymes
The IF-Cbl complex transits to the ileum where it is bound to ileal receptors
The IF-Cbl complex enters the ileal absorptive cell, B12 is released and enters the plasma
In the plasma B12 is becomes bound to transcobalamin which delivers the complex to non intestinal cells –> in cell it is freed from trasnport protein.
Deficiency in B12 –. impairs erythropoesis –> B12 needed for DNA synthesis, leads to megaloblastic anaemia (cells cannot complete DNA synthesis and remain larger). Also needed for heme synthesis, therefore hypchromic due to less Hb
For B12 absorption what is required?
What can cause pernicious anaemia?
For adequate vitamin B12 absorption you need: 1) adequate diet 2) functioning gastric parietal cells (for acid secretion and IF) 3) exocrine pancreas (that allows digestion of R factor, allow B12 to bind IF, 4) functioning ileum (for absorption at terminal ileum).
Causes of pernicious anaemia: Inadequate intake, loss of gastric mucosa (e.g. gastrectomy or hypchlorhydria) , functionally abnormal IF, inadequate proteolysis of B12, inusuffieient pancreatic protease, bacterial overgrowth - competes for b12, tapeworm (competes), disorder of ileum, disorder of plasma transport
What are the complications of vitamin B12 deficiency?
- Anaemia (megaloblastic anaemia)
- complicatino of anaemia itself –> tachyc and HF
- glossitis
- GI sx –> due to underlying disease?
- Neurological symptoms:
- subacute combined degeneration of the spinal cord (SACD) = patchy loss of myelin in dorsal and lateral columns of the spinal cord due to b12 defiency
- This is progressive –> weakness in arms/ legs/ trunk
- tingling and numbness
- vision changes
- change of mental state
- peripheral neuropathy
- ataxia
- dementia and memory loss
- seizures
- subacute combined degeneration of the spinal cord (SACD) = patchy loss of myelin in dorsal and lateral columns of the spinal cord due to b12 defiency
- Infertility and Neural tube defects for unborn fetus (Spina bifida, anencephaly, encephalocele)
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