Med 2 Core conditions

Question 1

Explain Acute renal disease/AKI

Answer 1

Acute kidney injury

• AKI = kidneys suddenly stop working properly. (range from minor loss of kidney function to complete kidney failure)
• Usually is a complication of another serious illness
• Without quick treatment, abnormal levels of salts and chemicals can build up in the body affecting the ability of other organs to function
• Symptoms
  
  • Nauseous
  • Diarrhoea
  • Dehydration
  • Peeing less than usual
  • Confusion
  • Drowsiness
• Risk factors
  
  • Age >65 years old
  • Already have a kidney problem
  • Long term diseases (e.g. heart failure, liver disease, diabetes)
  • Dehydrated
  • Blockage in urinary tract
  • Severe infection/sepsis
  • Taking NSAIDs, BP medications (ACE inhibitors, diuretics)
  • Aminoglycosides (type of antibiotic)
• Causes
  
  • Low BV (after bleeding, excessive vomiting, diarrhoea or dehydration)
  • HF, LF, sepsis
  • Vasculitis
  • Certain medications
  • Glomerulonephritis
  • Enlarged prostate
  • Bladder tumour
  • Kidney stones
• Diagnosis
  
  • Fits in a “at risk” group
  • Symptoms of AKI
  • Blood tests (HIGH creatinine in blood = AKI)
• Treatment
  
  • Increase water intake
  • Antibiotics (if infection)
  • Stop certain medications
  • Urinary catheter to drain bladder if blockage
• Complications
  
  • HIGH potassium in blood
    
    • Muscle weakness, paralysis and heart rhythm problems
    • Pulmonary oedema
    • Metabolic acidosis (nausea, vomiting, drowsiness and breathlessness)

Question 2

Nephrotic syndrome

Answer 2

• Kidney disorder that causes your body to pass too much protein in your urine
• Usually caused by damage to the glomeruli in the kidneys that filters waste and excess water from your blood
• Treatment
• Treating the condition that is causing nephrotic syndrome
• Increases the risk of infections and blood clots
• Symptoms
  
  • Oedema in feet and eyes
  • Foamy urine (as excess protein, proteinuria)
  • Weight gain due to fluid retention
  • Fatigue
  • Loss of appetite
• Causes
  
  • Diabetic kidney disease
  • Minimal change disease
    
    • Results in abnormal kidney function
  • Focal segmental glomerulosclerosis
    
    • Scarring of some glomeruli
  • Membranous nephropathy
    
    • Thickening membranes within the glomeruli
  • Systemic lupus erythematous
  • Amyloidosis
    
    • Amyloid proteins accumulate in the organs (damaging filtration system)
• Risk factors
  
  • Medical conditions (e.g. diabetes, lupus, amyloidosis)
  • Certain medications
    
    • (NSAIDs)
  • Certain infections
    
    • HIV, Hep B, C and malaria
• Complications
  
  • Blood clots (loss of blood proteins for clotting)
  • High blood cholesterol and blood triglycerides (as more albumin is made hence, more cholesterol made)
  • Poor nutrition
  • HIGH BP (as more fluid accumulation
  • Acute kidney injury
  • Chronic kidney disease
  • Infections

Question 3

Diabetes

Answer 3

• Diabetes Mellitus*
• A disorder of carbohydrate metabolism leading to abnormally high blood glucose levels (hyperglycaemia)
• Type 1 diabetes*
• Is an autoimmune disease in which the insulin producing beta cells of the Islets of Langerhans of the pancreas are destroyed or damaged, thought to be triggered by a viral environmental factor meaning that little/no insulin can be produced
• The environmental /infective trigger results in:
  
  • Insulitis -> invasion of pancreatic islets by T-lymphocytes leading to B-cell destruction, commonly then producing islet cell antibodies
• Typically starts in childhood/adolescence (often known as the disease of rapid onset)

Type 2 diabetes

• Is genetically determined resistance to insulin action on target tissues primarily the liver, skeletal muscle and adipose tissues
• Insulin resistance can be defined as the inability to produce its usual biological actions at circulating concentrations that are effective in normal subjects
• Resistance in adipose tissue increases NEFA causing increase resistance of liver and skeletal muscle to insulin
• As when glucose is absorbed by the gut this causes insulin levels to rise however, due to insulin resistance it means that it is hard for glucose to get into cells leading to hyperglycaemia and then, even higher levels of insulin to decrease blood glucose levels, leading to B-cells in the pancreas to over-work and die. Hence, over time there will be NO or little beta cells hence, these patients require insulin injections in worse prognosis (at first use metformin to increase the sensitivity of cells to insulin thus, decreasing blood glucose levels)

Question 4

Differential diagnosis of AKI

Answer 4

Question 5

When to biopsy the kidneys?

Answer 5

When to biopsy the kidneys

• To diagnose a suspected kidney problem
• To see how serious a problem really is
• Help develop treatment plans based on the kidney’s condition
• Determine progression of kidney disease and amount of damage
• Determine if kidney treatment is working
• Monitor health of transplanted kidney
• Blood in urine
• Proteinuria
• Problems with kidney function

Question 6

How to investigate AKI

Answer 6

How to investigate

• Arrange serum creatinine and eGFR blood tests (>60mL/min/1.73m^2)
• Arrange an early morning urine sample to measure albumin: creatinine ratio (ACR) (<3mg/mmol = no action needed)
• Arrange a urine dipstick to check for haematuria (+1 or more on blood on dipstick do more tests)
• Check nutritional status, BMI, BP, serum HbA1c and lipid profile
• Consider renal tract ultrasound

Question 7

Adrenal failure

Answer 7

• Adrenal failure – Primary Adrenal insufficiency (Addison’s disease)*
• Secondary adrenal insufficiency
• Primary adrenal insufficiency (occurs when adrenal gland is damaged thus, adrenal glands don’t make enough cortisol and aldosterone)*
• Destruction of the adrenal cortex leads to glucocorticoid (cortisol) and mineralocorticoid (aldosterone) deficiency
• K+ is high

Secondary adrenal insufficiency (when pituitary doesn’t make enough ACTH thus, adrenal gland doesn’t make enough cortisol)

• Common cause is iatrogenic
  
  • Due to long term steroid therapy leading to the suppression of the pituitary-adrenal axis (only becomes apparent of withdrawal of steroids

Tertiary adrenal insufficiency (when the hypothalamus doesn’t make enough CRH this adrenal glands don’t make enough cortisol)

• Symptoms
  
  • Fatigue
  • Muscle weakness
  • Low mood (depression, psychosis)
  • Loss of appetite
  • Unintentional weight loss
  • Increased thirst
  • Fluid loss
  • Low blood pressure
  • Low sugar levels
  • Women -> irregular or no menstrual periods
  • GI
    
    • Nausea/vomiting/abdominal pain/Diarrhoea/constipation
  • Postural hypotension
  • Pigmented palmar creases and buccal mucosa (HIGH ACTH cross-reacts with melanin receptors)
• Signs
  
  • ACTH stimulation test shows LOW cortisol
  • Baseline cortisol levels low
  • Fasting blood sugars low
  • Serum K+ elevated (primary adrenal insufficiency)
  • Serum Na+ is low (primary adrenal insufficiency)
• Signs of critical deterioration
  
  • Shock (LOW BP and tachycardia)
  • Coma
  • Raised temperature
• Risk factors
  
  • Physical stress e.g., infection, dehydration, trauma, adrenal or pituitary gland injury
  • Ending treatments with steroids e.g., prednisolone/hydrocortisone too early.
• Management
  
  • Replace steroids (hydrocortisone daily)
  • Mineralocorticoids to correct postural hypotension,
  • Low Na+, HIGH K+ fixed by fludrocortisone PO

Question 8

Addisonian Crisis

Answer 8

• Assessment
  
  • Bloods for cortisol and ACTH (straight to the laboratory and call ahead)
    
    • Low cortisol and HIGH ACTH (primary/ Addison’s disease)
  • U&Es as can have high K+ (check ECG) and LOW Na+ (salt depletion -> should resolve with rehydration and steroids)
  • Blood, urine sample for culture then antibiotics if concerned about infection
• Management
  
  • If suspected treat before biochemical results
  • Hydrocortisone
  • IV fluid bolus
  • Monitor blood glucose

Question 9

Effect of long-term steroids

Answer 9

• Only prescribed if potential benefits outweigh the risks (will be prescribed at the lowest possible dose for the shortest time)
• Side effects
  
  • Increase appetite (possible weight gain)
  • Acne
  • Glaucoma
  • Cataracts
  • Moon face
  • High blood sugar
  • Increase risk of infection
  • Thinned skin that bruises easily
  • Increased risk of infections
  • Mood changes, mood swings and depression
  • Diabetes
  • High blood pressure
  • Osteoporosis
  • Withdrawal symptoms caused by suppression of the adrenal glands)

Question 10

Addison’s Disease

Answer 10

• Addison’s disease, also called adrenal insufficiency, is an uncommon disorder that occurs when your body doesn’t produce enough of certain hormones. In Addison’s disease, your adrenal glands, located just above your kidneys, produce too little cortisol and, often, too little aldosterone
• Addison’s disease is caused by damage to your adrenal glands, resulting in not enough of the hormone cortisol and, often, not enough aldosterone as well. Your adrenal glands are part of your endocrine system. They produce hormones that give instructions to virtually every organ and tissue in your body.
• Your adrenal glands are composed of two sections. The interior (medulla) produces adrenaline-like hormones. The outer layer (cortex) produces a group of hormones called corticosteroids. Corticosteroids include:
  
  • Glucocorticoids. These hormones, which include cortisol, influence your body’s ability to convert food into energy, play a role in your immune system’s inflammatory response and help your body respond to stress.
  • Mineralocorticoids. These hormones, which include aldosterone, maintain your body’s balance of sodium and potassium to keep your blood pressure normal.
  • Androgens. These male sex hormones are produced in small amounts by the adrenal glands in both men and women. They cause sexual development in men, and influence muscle mass, sex drive (libido) and a sense of well-being in both men and women.

Question 11

Adrenal excess

Answer 11

• Adrenal excess*
• Symptoms depend on which hormone is being overproduced:*
• Androgenic steroids (androgen hormones)
  
  • Hormones related to testosterone
  • Can lead to strong male traits in both women in men
    
    • Extra hair growth on the face and body
    • Baldness
    • Acne
    • Deeper voice
    • More muscle mass
• Cortisol
  
  • Too much = Cushing’s syndrome
  • Fragile skin
  • Skin that bruises easily
  • Purple abdominal striae
  • Upper body obesity
  • Increased fat around the neck
  • Thin arms and legs
• Aldosterone
  
  • HIGH aldosterone – HIGH blood pressure
  • LOW K+
  • Result in weakness, muscle aches, spasms and sometimes paralysis
• Adrenaline
  
  • High blood pressure
  • Sudden and severe headaches and anxiety symptoms
• Treatment depend on symptoms, age and general health. Treatment depends on the cause.*
• Adrenal cortex ->*
• Produces steroids (glucocorticoids e.g. cortisol) which affect carbohydrate, lipid and protein metabolism
• Produces mineralocorticoids which control sodium and potassium balance e.g. aldosterone
• Androgens -> sex hormones which have a weak effect until peripheral conversation with testosterone and dihydrotestosterone.
• CRH (corticotropin-releasing hormone) from hypothalamus stimulates ACTH production by the adrenal cortex

Question 12

Cushing’s syndrome

Answer 12

• Cushing’s syndrome (excess corticosteroids)
  
  • Clinical state produced by chronic glucocorticoid excess and loss of the normal feedback mechanisms of the hypothalamic-pituitary adrenal axis and loss of circadian rhythm of cortisol secretion
  • Main cause are oral steroids as well as pituitary adenoma
  • Due to HIGH ACTH
• Symptoms
  
  • HIGH weight
  • Mood change
    
    • Depression, lethargy, irritability, psychosis)
  • Proximal weakness
  • Gonadal dysfunction (irregular masses, hirsutism, ED)
  • Acne
  • Recurrent Achilles rupture
• Signs
  
  • Central obesity
  • Plethoric
  • Moon face
  • Buffalo hump
  • Skin and muscle atrophy
  • Bruises
  • Purple abdominal striae
  • Osteoporosis
  • HIGH BP
  • HIGH glucose
  • Infection prone
  • Poor healing
• Risk factors
  
  • Taking HIGH doses of corticosteroids over a long period of time
  • Type 2 diabetes that isn’t properly managed
  • High blood pressure
  • Obesity
• Management
  
  • Iatrogenic
    
    • Stop medication if possible
  • Cushing’s disease
    
    • Removal of pituitary adenoma
  • Adrenal adenoma or carcinoma
    
    • Adrenalectomy
    • Radiotherapy and adrenolytic drugs
  • Ectopic ACTH
    
    • Surgery if tumour is located and hasn’t spread

Question 13

Endogenous vs exogenous Cushing’s syndrome

Answer 13

Exogenous Cushing syndrome (the role of corticosteroid medications)

• Cushing syndrome developed from taking oral corticosteroid medications (e.g. prednisolone, high doses over time)
• Inhaled corticosteroids for asthma and steroid creams for skin disorders = less likely (can happen if taken in high doses for long periods of time

Endogenous Cushing syndrome (body’s own overproduction)

• Due to body producing either too much cortisol or too much adrenocorticotropic hormone (ACTH)
• In these cases Cushing syndrome can be related to:
  
  • Pituitary adenoma
    
    • Benign tumour in pituitary gland, produces excess amount ACTH -> stimulates adrenal gland to make more cortisol
    • More common in women (and is the most common cause)
  • An ACTH secreting tumour
    
    • Tumour that develops in an organ that previously didn’t make ACTH now makes ACTH (usually lungs, pancreas, thyroid or thymus gland)
  • Primary adrenal gland disease
    
    • Disorder of adrenal gland -> produce too much cortisol
  • Familial Cushing syndrome
    
    • Inherit tendency to develop tumours on one or more of their endocrine glands affecting cortisol levels and causing Cushing syndrome

Question 14

Anaemia

Answer 14

• Anaemia has been linked with the development of cardiomyopathies
  
  • Predisposes individuals to initial left ventricular dilation with compensatory hypertrophy which may progress into systolic dysfunction
  • Usually these patients have problems with kidneys hence, leading to dialysis
• Iron deficiency predisposes individuals to pulmonary arterial hypertension (PAH).
  
  • In this condition the vasculature of the lungs is constricted and remodelled hence, putting pressure on the right side of the heart
  • Iron deficiency in the smooth muscles cells of the pulmonary arteries is enough to cause PAH
    
    • Effect of iron deficiency increased due to vasoconstrictor endothelin-1 from cells of the pulmonary arteries
• Decreased oxygen delivery by the cardiovascular system can cause heart and brain damage and in some cases death
• HR increases as heart needs to pump the available red blood cells more quickly around the system for the cells to stay alive
• Is defined as the low haemoglobin concentration (Hb) and may be due to either a low red cell mass or increased plasma volume (e.g. in pregnancy).
• A low Hb concentration (at sea level) is <135g/L in men and <115g/L for women.
• Can be due to reduced production or increase loss of RBC and has many causes

Symptoms

• Fatigue
• Dyspnoea
• Faintness
• Palpitations
• Headache
• Tinnitus
• Anorexia
• Angina (if pre-existing coronary artery disease)

Signs

• Pallor
• Tachycardia
• Flow murmurs
• Cardiac enlargement
• Retinal haemorrhages

Types of anaemia

• Low MCV (microcytes anaemia)
• Normal MCV (normocytic anaemia)
• High MCV (macrocytic anaemia)

Haemolytic anaemia

Cardio-respiratory effect of anaemia

• Anaemia -> most common disease that may increase the cardiac output at rest
  
  • Decreases oxygen carrying capacity of blood and decreases viscosity as well
  • In chronic anaemia increased cardiac output principally reflects a larger cardiac stroke volume (since tachycardia is commonly not found)
• Have low haematocrit (a measure of the volume of red blood cells in blood)
• Causes decreased oxygen delivery to tissues (in particular muscle tissues)

Question 15

Iron deficiency anaemia

Answer 15

• Iron deficiency predisposes individuals to pulmonary arterial hypertension (PAH).
  
  • In this condition the vasculature of the lungs is constricted and remodelled hence, putting pressure on the right side of the heart
  • Iron deficiency in the smooth muscles cells of the pulmonary arteries is enough to cause PAH
    
    • Effect of iron deficiency increased due to vasoconstrictor endothelin-1 from cells of the pulmonary arteries

Question 16

GI-bleeding (initial assessment and management)

Answer 16

Question 17

Interpretation of blood tests (endocrinological

Answer 17

• Endocrinological blood tests:
  
  • HbA1C (glycosylated haemoglobin test to detect diabetes and prediabetes)
    
    • Below 42mmol/mol
  • Glucose tolerance test to screen for gestational diabetes
    
    • Oral one takes 2 hours and have to have fasted for 8-10 hours prior
    • If blood glucose is higher than 10.6mmol/L or 190mg/dL after 1 hour of the test = gestational diabetes
  • Bone density test
    
    • Good between +1 and -1 SD
  • TSH blood test
    
    • Normally 0.4 to 4mU/L (high = hypothyroidism)
  • LH
    
    • Men = 1.42-15.4IU/L
    • Women = 1.37 to 9IU/L
  • FSH
    
    • Adult = 1.5 to 12.4IU/L)
  • Testosterone
    
    • Male 280 and 1,100ng/dL
  • Cortisol
    
    • 6 to 8am = 10-20mcg/dL and around 4pm = 3 to 10mcg/dL
  • 17 hydroxyprogesterone
  • DHEA-sulphate
    
    • Aged 18-19 = 145-395ug/dL
  • ACTH
    
    • 6-76pg/ml
  • Aldosterone
    
    • 2-9ng/dL
  • Vitamin D
    
    • 20-50ng/ml
  • PTH (Parathyroid test)
    
    • 14-65pg/ml
  • Prolactin
    
    • Males = 2-28ng/ml
    • Females (not pregnant) = 2-29ng/ml
    • Females (pregnant) = 10-209ng/ml
  • Oestrogen
    
    • Women = 15-350pg/ml
  • Thyroglobulin levels (Tg) – monitor thyroid cancer
    
    • 5ug/L or above
    • If thyroglobulin range rises with time and TSH does not rise means that likely thyroid cancer
• Thyroid function tests
  
  • TSH, T4, T3 (good measure FT4, FT3 → FT4 more important because more is made & is converted to T4 peripherally
• Antibodies
  
  • _TSH-ab_ (+ve in 70-100% of Graves & Hashimoto’s) → Graves
  • _TPO-ab_ (+ve in ~70% of Graves & -ve (or normal) in Hashimoto’s) → Autoimmune
• Imaging
  
  • Thyroid uptake scan (raised uptake in Graves) OR (reduced uptake → thyroiditis, Hashimoto’s & excess iodine intake)

Question 18

Oesophageal cancer (nutritional issues)

Answer 18

• Oesophageal cancer
  
  • Cancer in the oesophagus
  • Usually begins in the cells that line the inside of the oesophagus
  • More men than women get oesophageal cancer
• Symptoms
  
  • Dysphagia
  • Weight loss
  • Chest pain, pressure or burning
  • Worsening indigestion or heartburn
  • Coughing or hoarseness
• Causes
  
  • Unknown
  • Mutations of DNA of cells in oesophagus make cells grown and divide out of control
  • Accumulating cells form tumour and grown and invade nearby structures
• Types
  
  • Adenocarcinoma
    
    • Begins in the mucus-secreting glands of the oesophagus (usually lower portion)
  • Squamous cell carcinoma
    
    • Most often in the upper and middle portions of the oesophagus
  • Other rare types
    
    • Small cell carcinoma, sarcoma, lymphoma, melanoma and choriocarcinoma
• Risk factors
  
  • GERD
  • Smoking
  • Barrett’s oesophagus (changes in the cells of the oesophagus)
  • Being obese
  • Drinking alcohol
  • Bile reflux
  • Achalasia (dysphagia due to oesophageal sphincter that won’t relax)
  • Not eating enough fruits and vegetables
  • Radiation treatment to chest or upper abdomen
• How does oesophageal cancer affect nutrition?
  
  • Loss of appetite
  • Dryness, sores and pain in throat and oesophagus
  • Not being able to swallow
  • Nausea and vomiting
  • Treatment
    
    • A soft, high protein diet
    • NG tube
    • PEG
    • Parental nutrition through IV drip

Question 19

Stomach cancer (nutritional issues)

Answer 19

Stomach cancer (gastric cancer)

• Abnormal growth of cells that begin in the stomach
• Symptoms
  
  • Difficulty swallowing
  • Feeling bloated after eating
  • Feeling full after eating small amounts of food
  • Heart burn
  • Indigestion
  • Nausea
  • Stomach pain
  • Unintentional weight loss
  • Vomiting
• Causes
  
  • Changes in cells DNA (grow quickly and divide quickly)
• Risk factors
  
  • GERD
  • Obesity
  • Diet high in salty and smoked foods
  • Diet low in fruits and vegetables
  • Family history of stomach cancer
  • Infection with H.pylori
  • Gastritis
  • Smoking
  • Stomach polyps
• How does stomach cancer affect nutrition?
  
  • Weight loss is common with people with stomach cancer
    
    • Can cause blockages, interfering with the passage of food into the stomach from the oesophagus or stomach to intestines (difficult for person to eat)
  • People with stomach cancer often have loss of appetite and may not like eating
  • After stomach cancer surgery, may not be able to eat large meals as will feel full, usually due to how much of the stomach is removed
  • Stomach may not be able to digest and absorb nutrients depending on amount of stomach removed
  • Dumping syndrome – condition that causes food or liquid to move through stomach and small intestine too quickly

Question 20

Chronic kidney disease

Answer 20

Pathophysiology

• Chronic kidney disease
  
  • Gradual loss of kidney function
  • Can cause dangerous levels of fluid, electrolytes and waste to build up in the body
  • 1) Kidney damage for ≥ 3 months, as defined by structural or functional abnormalities of the kidney, with or without decreased GFR, manifest by either :
    
    • Pathological abnormalities on kidney biopsy ir
    • Markers of kidney damage, such as proteinuria, abnormal urinary sediment, or abnormalities in imaging tests
  • 2) GFR < 60 mL/min/1.73m 2 for ≥ 3 months, with or without kidney damage
  • Symptoms
    
    • Nausea
    • Vomiting
    • Loss of appetite
    • Fatigue and weakness
    • Sleep problems
    • Polyuria or less urine
    • Decreased mental sharpness
    • Muscle cramps
    • Oedema of feet
    • Dry itchy skin
    • HIGH BP
    • SOB
    • Chest pain
  • Causes:
    
    • Type 1/Type 2 diabetes
    • HIGH BP
    • Glomerulonephritis
    • Interstial nephritis
    • Polycystic kidney disease
    • Prolonged urinary tract obstruction
    • Vesicoureteral reflux
    • Recurrent kidney infection

Question 21

Glomerulonephritis

Answer 21

Glomerulonephritis

• Inflammation of the glomeruli
• Can occur on its own or part of another disease e.g. diabetes or lupus
• Symptoms
  
  • Pink or cola-coloured urine from RBC (haematuria)
  • Foamy urine due to proteinuria
  • Hypertension
  • Oedema (hands, feet, abdomen)
• Causes:
  
  • Post-streptococcal glomerulonephritis (after a strep throat infection)
  • Bacterial endocarditis
  • Viral infections
• Can cause chronic kidney disease due to damage to the glomeruli and then progress to end-stage kidney disease

Question 22

Differential diagnosis of chronic kidney disease

Answer 22

Differential diagnosis

• AKI
• Alport syndrome
• Antiglomerular basement membrane disease
• Chronic glomerulonephritis
• Diabetic nephropathy
• Multiple myeloma
• Nephrolithiasis
• Rapidly progressive glomerulonephritis
• Polycystic kidney disease

Question 23

When to biopsy in chronic kidney disease?

Answer 23

When to biopsy in CKD

• Haematuria
  
  • Blood in urine
• Albuminuria
  
  • Urine has more than normal amounts of albumin
• Changes in kidney function which can cause the build-up of waste products in the blood

Question 24

How to investigate chronic kidney disease?

Answer 24

When to investigate in CKD

• Blood tests
  
  • U&Es e.g. creatinine and urea
• Urine tests
  
  • Reveal abnormalities that indicate chronic kidney failure
• Imaging test
  
  • Ultrasound to assess kidney’s structure and size
• Removing a sample of kidney tissue for testing
  
  • Biopsy done and sent to the lab to determine what is causing the kidney problem

Question 25

Chronic liver disease

Answer 25

Chronic liver disease

• Is marked by the gradual destruction of the liver tissue over time
• Types:
  
  • Cirrhosis
    
    • Scar tissue slowly replaces normal functioning liver tissue
    • Scar tissue progressively diminished the flow of blood through the liver
    • As normal liver tissue is lost the lover can no longer effectively process nutrients, hormones, drugs and poisons
    • Liver cannot effectively produce proteins and other substances
  • Fibrosis of the liver
    
    • Growth of scar tissue due to infection, injury or even healing
    • Can prevent organ functioning (liver fibrosis is usually a result of cirrhosis)

Question 26

Alcoholic liver disease

Answer 26

• Stages of ARLD (alcoholic related liver disease)
  
  • Alcoholic fatty liver disease (stage 1)
    
    • It is reversible as it is just the build-up of fats in the liver
    • As when alcohol is metabolised it results in the overproduction of fat in the liver (healthy live should have little or NO fat
  • Alcoholic hepatitis (stage 2)
    
    • Usually, the first time someone is aware they are damaging their liver through alcohol
    • Usually, reversible
    • Liver becomes inflamed, swollen and tender
  • Cirrhosis (stage 3)
    
    • Generally, not reversible (but stopping drinking alcohol immediately can prevent further damage and significantly increase life expectancy)
    • Nodules produced and shape of the liver becomes distorted

Question 27

Oesophageal varices (link with chronic liver disease)

Answer 27

• Most common cause is cirrhosis
• Blood flow to liver slows down due to scarring causing increase in portal vein pressure (portal hypertension)
• This increases pressure in surrounding blood vessels including the oesophagus
• These blood vessels have thin walls and are close to the surface and then, they expand and swell
• If pressure caused by extra blood gets high these varices break open and bleed

Question 28

Coagulation disorders (clotting in liver disease)

Answer 28

Clotting in liver disease

• Liver is the site of synthesis of ALL the coagulation factors except for vWF
• Liver damage is commonly associated with impairment of coagulation
• Liver failure causes multiple changes in the haemostatic system (coagulation system, endothelium, regulatory proteins, platelets and fibrinolysis), due to reduced plasma levels of procoagulant and anticoagulant factors synthesised by the intact liver
• Thrombocytopenia (due to decreased hepatic thrombopoietin synthesis and splenomegaly due to portal hypertension)
• Alterations in the quantity and quality of coagulation factors and platelets lead to a propensity for bleeding and simultaneous thrombosis
• Decrease in platelets numbers and functionally different (as NO released due to portal hypertension -> as these inhibit clot formation by platelets)
• Majority of coagulation factors made in the liver (factor VIII made in liver but also in the lungs, endothelial cells and spleen)
  
  • INCREASE in production of factor VIII causes increase in thrombin hence, causes increase risk of thrombosis (hypercoagulability)

Congenital

1. Haemophilia A
   
   1. Factor VIII deficiency
   2. Inherited in an X-linked recessive pattern
   3. High rates of new random mutations
   4. Presentation
      
      1. Depends on severity
      2. Seen when surgery or trauma
      3. Bleeding into joints -> crippling arthropathy
      4. Bleeding into the muscles causing hematomas (INCREASE pressure = compartment syndrome & nerve palsies)
      5. Diagnose
         
         1. HIGH APTT
         2. LOW factor VIII assay
      6. Management
         
         1. Avoid NSAIDs & IM injections
         2. Minor bleeding -> pressure and elevation of part
         3. Desmopressin raises factor VIII levels)
            
            1. Life threatening levels require higher levels of desmopressin
      7. Genetic counselling helpful (OHCP)
   5. Haemophilia B (Christmas disease)
      
      1. Factor IX deficiency (inherited, X linked recessive)
      2. Behaves typically like haemophilia A
      3. Treat
         
         1. *Recombinant factor IX*
   6. Acquired haemophilia
      
      1. Bleeding diathesis causing big mucosal bleeds caused by suddenly appearing autoantibodies that interfere with factor VIII
      2. Tests
         
         1. HIGH APPT
         2. HIGH VIII autoantibodies
         3. Factor VIII activity <50%
      3. Management
         
         1. Steroids
   7. Von Willebrand’s disease

Acquired

1. Anticoagulants
2. Liver disease
   
   1. Produces a complicated bleeding disorder with LOW synthesis of clotting factors, LOW absorption of vitamin K and abnormalities of platelet function
   2. DIC (disseminated intravascular coagulation)
      
      1. Blood clots form throughout the body, blocking small blood vessels
      2. Symptoms:
         
         1. Chest pain
         2. SOB
         3. Leg pain
         4. Problems seeing
         5. Problems moving parts of body
   3. Vitamin K deficiency
   4. Malabsorption
      
      1. Leads to less uptake of vitamin K (needed for synthesis of factors II, VII, IX and X)
      2. Treat
         
         1. IV vitamin K
         2. In acute haemorrhage use human prothrombin complex or FFP

Question 29

Transfusion in acute blood loss

Answer 29

Essentials

• Avoid unnecessary and inappropriate transfusions.
• Preventable ‘wrong blood into patient’ incidents are nearly always caused by human error and may cause fatal reactions due to ABO incompatibility.
• Most mistransfusion incidents are caused by identification errors at the time of pre-transfusion blood sampling, sample handling in the laboratory, collecting the wrong component from the blood bank or transfusion to the patient.
• The identity check between patient and blood component is the crucial final opportunity to avoid potentially fatal mistransfusion.
• At every stage of the blood administration process the key elements are positive patient identification, excellent communication and good documentation. These can be enhanced by the use of electronic transfusion management systems and barcode technology.
• Hospitals should develop local transfusion policies based on national guidelines and ensure all staff involved in the clinical transfusion process are appropriately trained and competency assessed.
• Where possible, patients should give ‘valid consent’ for transfusion based on appropriate information and discussion, but signed consent is not a legal requirement.
• Non-essential ‘out of hours’ requests for transfusion and overnight administration of blood should be avoided wherever possible because of an increased risk of errors.

Question 30

Diabetes (type 1 and type 2)

Answer 30

• Diabetes mellitus is a chronic heterogeneous metabolic disorder with complex pathogenesis. It is characterized by elevated blood glucose levels or hyperglycaemia, which results from abnormalities in either insulin secretion or insulin action or both. Hyperglycaemia manifests in various forms with a varied presentation and results in carbohydrate, fat, and protein metabolic dysfunctions. Long-term hyperglycaemia often leads to various microvascular and macrovascular diabetic complications, which are mainly responsible for diabetes-associated morbidity and mortality. Hyperglycaemia serves as the primary biomarker for the diagnosis of diabetes as well.*
• Epidemiology of diabetes*
• Type 1 diabetes
  
  • Geography
    
    • Incidence of type 1 diabetes is highest in Sardinia, Finland, Sweden, Kuwait, Canada, Norway
    • Europe and North America have either high or intermediate incidences of T1 DM
    • Africa is generally intermediate incidence of T1 DM
    • Asia is generally low (except Kuwait) incidence of T1 DM
  • Age, sex and ethnicity
    
    • Highest incidence of borth-14 years old
    • Slightly more males and peak when hit puberty
    • Higher incidence in European countries
  • Aetiological factors
    
    • Genetic susceptibility is important (not sufficient though)
• Type 2 diabetes
  
  • Variation in prevalence by geographical location, ethnicity, age and sex
    
    • Prevalence is lowest in rural areas of developing countries
    • Intermediate prevalence in developed countries
    • Highest prevalence in certain ethnic groups (particularly those who have adopted to the Western lifestyle patterns)
      
      • x4/6 more prevalent in South Asians and African-Caribbean in the UK vs European white populations
    • Increase prevalence with age
    • Slightly more men than women diagnosed
  • Aetiological factors
    
    • Insulin resistance and a relative insulin secretory deficit
    • Age
    • Obesity
    • Family history
    • Physical inactivity
    • Increase risk with consumption of red and processed meat, sugar-sweetened beverages, reduced intake of fruit and vegetables, some types of dairy products
• Diabetes Mellitus*
• A disorder of carbohydrate metabolism leading to abnormally high blood glucose levels (hyperglycaemia)
• Type 1 diabetes*
• Is an autoimmune disease in which the insulin producing beta cells of the Islets of Langerhans of the pancreas are destroyed or damaged, thought to be triggered by a viral environmental factor meaning that little/no insulin can be produced
• The environmental /infective trigger results in:
  
  • Insulitis -> invasion of pancreatic islets by T-lymphocytes leading to B-cell destruction, commonly then producing islet cell antibodies
• Typically starts in childhood/adolescence (often known as the disease of rapid onset)

Type 2 diabetes

• Is genetically determined resistance to insulin action on target tissues primarily the liver, skeletal muscle and adipose tissues
• Insulin resistance can be defined as the inability to produce its usual biological actions at circulating concentrations that are effective in normal subjects
• Resistance in adipose tissue increases NEFA causing increase resistance of liver and skeletal muscle to insulin
• As when glucose is absorbed by the gut this causes insulin levels to rise however, due to insulin resistance it means that it is hard for glucose to get into cells leading to hyperglycaemia and then, even higher levels of insulin to decrease blood glucose levels, leading to B-cells in the pancreas to over-work and die. Hence, over time there will be NO or little beta cells hence, these patients require insulin injections in worse prognosis (at first use metformin to increase the sensitivity of cells to insulin thus, decreasing blood glucose levels)

Question 31

Electrolyte and water balance

Answer 31

Electrolyte and water balance

• Levels of electrolytes in your body can become too low or too high
  
  • Can happen when the amount of water in your body changes
  • Water take in should be equal to the amount lost
  • If balance affected may have too little (dehydration) or too much (overhydration)
• Kidneys essential for regulating volume and composition of bodily fluids

Question 32

Electrolyte and water balance (GI bleeding)

Answer 32

GI bleeding

• Loss of gastric contents usually results in excessive loss of chloride (and loss of sodium and potassium)

Question 33

Electrolyte and water balance (Nephrotic syndrome)

Answer 33

Nephrotic syndrome

• In early stages seen oliguria, retention of sodium and water with oedema and alterations of concentrations of sodium, potassium or calcium in the blood
• Later acidosis, anaemia and hypertension

Question 34

Electrolyte and water balance (malnutrition)

Answer 34

Malnutrition

• All have deficiencies in magnesium and potassium
• Oedema is a result of potassium deficiency and sodium retention (DO NOT treat oedema with diuretic)
• Excess body sodium exists even though the plasma sodium may be low

Question 35

Electrolyte and water balance (electrolyte disorders)

Answer 35

Electrolyte disorders

• Types of electrolyte disorders
  
  • Calcium: hypo/Hypercalcaemia
  • Chloride: hypo/hyperchloraemia
  • Magnesium: hypo/hypermagnesaemia
  • Phosphate: hypo/hyperphosphatemia
  • Potassium: hypo/hyperkalaemia
  • Sodium: hypo/hypernatraeemia

Question 36

Electrolyte and water balance (Cushing’s syndrome)

Answer 36

Cushing’s syndrome

• Marked electrolyte imbalance is present
• Severe hypokalaemia (alkalosis) and hypernatraemia and hyperchloraemia (can result in disorientation, coma and death)

Question 37

Electrolyte and water balance (Conn’s syndrome)

Answer 37

Conn’s syndrome (primary aldosteronism)

• Rare condition caused by overproduction of aldosterone that controls sodium (hypernatraemia) and potassium (hypokalaemia)

Question 38

Hypertension

Answer 38

Hypertension

• Is high blood pressure usually over 140/90mmHg

Question 39

Hypertension (secondary causes)

Answer 39

Secondary causes

• High blood pressure caused by another condition or disease
• Examples:
  
  • Kidney disease
  • Adrenal disease
  • Thyroid problems
  • Obstructive sleep apnea
  • Hyperparathyroidism

Question 40

Hypertension (renal)

Answer 40

• Kidney disease
• Injury to kidney/arteries that are too narrow can lead to poor blood supply to the organ
• Can trigger high production of renin
  
  • Renin -> angiotensin II (through steps) then causes increase in pressure through RAAS

Question 41

Hypertension (endocrine)

Answer 41

Endocrine

• Adrenal disease
  
  • Pheochromocytoma
    
    • Tumour of adrenal gland that overproduces adrenaline
  • Conn’s syndrome
    
    • Body makes too much aldosterone
  • Cushing’s syndrome
    
    • Too much cortisol in the body
• Hyperparathyroidism
  
  • Overproduction of hormones that control calcium levels in blood hence, lead to high blood pressure
• Thyroid problems
  
  • Abnormal thyroid function may lead to high BP as T3 causes high BP

Question 42

Inflammatory bowel disease

Answer 42

• Inflammatory bowel disease – term used to describe disorders that involve chronic inflammation of the GI tract*
• Examples of IBD:*
• Ulcerative colitis (inflammation and ulcers along large intestine and rectum)
• Crohn’s disease (inflammation of the lining of the GI tract)

Causes of IBD

• Genetics
• Immune system response (immune system mistakes foods as foreign substances and releases antibodies to fight off this threat)
• Environmental triggers
  
  • Smoking, stress,

Non-inflammatory GI diseases

• Microscopic colitis
  
  • Causes:
    
    • Genes and abnormal immune reactions
    • Certain medicines and smoking increases the risk of disease
• Ischaemic colitis
  
  • Causes
    
    • Buildup of atherosclerosis
    • Hypotension associated with dehydration, heart failure, surgery, trauma and shock
    • Bowel obstruction caused by a hernia, scar tissue or tumour
    • Surgery involving the heart/blood vessels or the digestive/gynecological systems
    • Vasculitis, lupus or sickle cell anaemia
    • Cocaine/methamphetamine
    • Colon cancer
• Segmental colitis associated with diverticula
  
  • Causes
    
    • Local colonic ischaemia, faecal stasis or mucosal prolapse
• Radiation colitis
  
  • Causes
    
    • Ionizing radiation (damages intra and extracellular structures by ionizing molecules, radiolysis, and the formation of free radicals by water -> causes damage to the cell membrane, organelles and DNA -> single and double strand breaks in DNA and dimer formation
    • A larger, quick dose of radiation has an increased risk of causing damage compared to several smaller doses spaces out over several days or weeks
• Diversion colitis
  
  • Causes
    
    • Changes in the bacterial composition of the defunctioned section of the colon
    • Due to reduction in nutrients delivered to the cells that live in the defunctioned colon after fecal matter has stopped passing through
    • The deprivation of one nutrient specifically, short chain fatty acids is thought to play a role in the development of diversion colitis
• Eosinophilic colitis
  
  • Causes
    
    • Cause mostly unknown
    • Cow’s milk protein often exacerbates symptoms
    • Family history of allergic disorders may be at higher risk of developing eosinophilic colitis
• Behcet’s colitis
  
  • Causes
    
    • Autoimmune disorder hence, body’s immune system mistakenly attacks some of its own healthy cells
    • Genetic (some genes have been associated with the disease) and environmental factors play a role
    • Some believe a virus/bacterium can trigger Behcet’s disease in people who contain certain genes that make them susceptible to Behcet’s

Question 43

Crohn’s disease

Answer 43

Pathophysiology of Crohn’s disease

• Crohn disease begins with crypt inflammation and abscesses, which progress to tiny focal aphthoid ulcers. These mucosal lesions may develop into deep longitudinal and transverse ulcers with intervening mucosal edema, creating a characteristic cobblestoned appearance to the bowel.
• Transmural spread of inflammation leads to lymphedema and thickening of the bowel wall and mesentery. Mesenteric fat typically extends onto the serosal surface of the bowel. Mesenteric lymph nodes often enlarge. Extensive inflammation may result in hypertrophy of the muscularis mucosae, fibrosis, and stricture formation, which can lead to bowel obstruction.
• Abscesses are common, and fistulas often penetrate into adjoining structures, including other loops of bowel, the bladder, or psoas muscle. Fistulas may even extend to the skin of the anterior abdomen or flanks. Independently of intra-abdominal disease activity, perianal fistulas and abscesses occur in 25 to 33% of cases; these complications are frequently the most troublesome aspects of Crohn disease.
• Noncaseating granulomas can occur in lymph nodes, peritoneum, the liver, and all layers of the bowel wall. Although pathognomonic when present, granulomas are not detected in about half of patients with Crohn disease. The presence of granulomas does not seem to be related to the clinical course.
• Segments of diseased bowel are sharply demarcated from adjacent normal bowel (called skip areas), hence the name regional enteritis.
  
  • About 35% of Crohn disease cases involve the ileum alone (ileitis).
  • About 45% involve the ileum and colon (ileocolitis), with a predilection for the right side of the colon.
  • About 20% involve the colon alone (granulomatous colitis), most of which, unlike ulcerative colitis, spares the rectum.

Crohn’s disease causes

• Exact cause of Crohn’s disease remains unknown
• Immune system
  
  • Virus/bacterium triggers Crohn’s disease possible cause
    
    • When immune system tries to fight off the invading microorganism, an abnormal immune response causes the immune system to attack the cells of the digestive tract too
• Heredity
  
  • Higher prevalence in individuals with family members who have Crohn’s disease

Question 44

IBD (weight loss)

Answer 44

• Malnutrition in IBD due to
  
  • Poor appetite
  • Food aversions
  • Malabsorption
  • Increase in calories in body burned to fight the disease and its complications
  • Nutrient losses due to diarrhoea or intestinal bleeding
• Intestinal inflammation and certain medications can make it difficult to maintain a healthy diet
• Small intestine inflammation
  
  • Can cause problems digesting food and absorbing nutrients
• Large intestine (including colon and rectum) inflammation
  
  • Problems absorbing water and electrolytes
• Crohn’s disease more likely to have nutritional problems than ulcerative colitis
• Symptoms that lead to weight loss:
  
  • Severe diarrhoea
    
    • Cause dehydration (depletion of fluids and electrolytes)
  • Abdominal pain and nausea
    
    • Can reduce appetite (makes it difficult to consume calories and sufficient nutrients
  • Rectal bleeding
    
    • From ulcers in intestines can lead to iron deficiencies and anaemia
  • Frequent bowel movements
    
    • Can cause decrease eating to avoid excess use of bathrooms hence, become malnourished

Question 45

Malabsorption

Answer 45

Malabsorption – disorder that occurs when people are unable to absorb nutrients from their diets e.g. carbohydrates, fats, minerals, proteins or vitamins (e.g. lactose intolerant, coeliac disease, as well as people with a history of bowel or stomach surgery)

Malabsorption – decreased intestinal absorption of carbohydrate, protein, fat, minerals or vitamins

• Due to malabsorption, you get diarrhoea, muscle wasting and weight loss
  
  • If not digesting or absorbing fats, proteins, or carbohydrates properly -> won’t get as many calories from the food you eat leading to weight loss

Pathophysiology of malabsorption

• Digestion and absorption occur in three phases:
  
  • Intraluminal hydrolysis of fats, proteins, and carbohydrates by enzymes—bile salts enhance the solubilization of fat in this phase
  • Digestion by brush border enzymes and uptake of end-products
  • Lymphatic transport of nutrients
• The term malabsorption is commonly used when any of these phases is impaired, but, strictly speaking, impairment of phase 1 is maldigestion rather than malabsorption.
• Digestion of fats
  
  • Pancreatic enzymes (lipase and colipase) split long-chain triglycerides into fatty acids and monoglycerides, which combine with bile acids and phospholipids to form micelles that pass through jejunal enterocytes. Absorbed fatty acids are resynthesized and combined with protein, cholesterol, and phospholipid to form chylomicrons, which are transported by the lymphatic system. Medium-chain triglycerides are absorbed directly.
  • Unabsorbed fats trap fat-soluble vitamins (A, D, E, K) and possibly some minerals, causing deficiency. Bacterial overgrowth results in deconjugation and dehydroxylation of bile salts, limiting the absorption of fats. Unabsorbed bile salts stimulate water secretion in the colon, causing diarrhoea.
• Digestion of carbohydrate
  
  • The pancreatic enzyme amylase and brush border enzymes on microvilli lyse carbohydrates and disaccharides into constituent monosaccharides. Colonic bacteria ferment unabsorbed carbohydrates into carbon dioxide, methane, hydrogen, and short-chain fatty acids (butyrate, propionate, acetate, and lactate). These fatty acids cause diarrhoea. The gases cause abdominal distention and bloating.
• Digestion of proteins
  
  • Gastric pepsin initiates digestion of proteins in the stomach (and also stimulates release of cholecystokinin that is critical to the secretion of pancreatic enzymes). Enterokinase, a brush border enzyme, activates trypsinogen into trypsin, which converts many pancreatic proteases into their active forms. Active pancreatic enzymes hydrolyse proteins into oligopeptides, which are absorbed directly or hydrolysed into amino acids.

Question 46

Malabsorption (assessment)

Answer 46

Assessment

• Doctor will ask patient about their symptoms
• Symptoms of malabsorption:
  
  • Bloating and stomach distention
  • Diarrhoea
  • Fatigue
  • Gas
  • Steatorrhea
  • Stool ‘grey’ in texture
  • Stomach cramping
  • Weakness
• Tests:
  
  • Blood tests
    
    • FBC
    • U&Es
    • Protein levels
  • Stool tests
    
    • High levels of fat = person not absorbing fat in their diet
  • Breath tests
    
    • Check presence of hydrogen gas in those who may be lactose intolerant
  • Imaging tests
  • Special tests
    
    • Endoscopy (doing biopsies as well)
    • Colonoscopy (doing biopsies as well)

Question 47

Malabsorption (coeliac)

Answer 47

Coeliac disease causes

• Genes combined with eating foods with gluten and other factors contribute
• Infant-feeding practices
• GI infections
• Gut bacteria
• Can become active after:
  
  • Surgery
  • Pregnancy
  • Childbirth
  • Viral infection
  • Severe emotional stress
• When the body’s immune system overreacts to gluten in food, the reaction damages the villi in the small intestine (prevent absorption of vitamins, minerals and nutrients hence, leading to malnutrition)

Common presentations of coeliac disease

• Diarrhoea
• Fatigue
• Weight loss
• Bloating and gas
• Abdominal pain
• Nausea and vomiting
• Constipation
• Pale, foul-smelling, or fatty stool
• Irritability and behavioural issues
• Dental enamel defects of permanent teeth
• Delayed growth and puberty
• Short stature
• Failure to thrive
• Attention deficit hyperactivity disorder (ADHD)

Atypical presentations of coeliac disease

• Anaemia (usually from iron deficiency)
• Osteoporosis or osteomalacia (softening of bone)
• Itchy, blistery skin rash (dermatitis herpetiformis)
• Mouth ulcers
• Headaches and fatigue
• Nervous system injury (numbness and tingling in the feet and hands, possible problems with balance and cognitive impairment)
• Joint pain
• Hypospenism (reduced functioning of the spleen)
• Chronic migraine
• Unexplained chronic hypertransaemina
• Late menarche/early menopause
• Unexplained fertility

How to investigate for coeliac disease

• 2 blood tests:
  
  • Serology testing
    
    • Looks for antibodies in blood. Elevated levels of certain antibody proteins indicate immune reaction to gluten
  • Genetic testing
    
    • For human leukocyte antigens (HLA-DQ1&8) can be used to rule out coeliac disease
  • Endoscopy
    
    • Camera goes down to view your small intestine and a biopsy will be taken from (damaged) villi
  • Capsule endoscopy
    
    • Camera sits inside a vitamin-sized capsule which is swallowed (thousands of pictures taken)

How to treat coeliac disease

• Strict, lifelong gluten-free diet
• Do not eat wheat, foods that contain gluten:
  
  • Barley
  • Bulgur
  • Durum
  • Farina
  • Graham flour
  • Malt
  • Rye
  • Semolina
  • Spelt (a form of wheat)
  • Triticale

Question 48

Malabsorption (Crohn’s)

Answer 48

Crohn’s

Pathophysiology of Crohn’s disease

• Crohn disease begins with crypt inflammation and abscesses, which progress to tiny focal aphthoid ulcers. These mucosal lesions may develop into deep longitudinal and transverse ulcers with intervening mucosal edema, creating a characteristic cobblestoned appearance to the bowel.
• Transmural spread of inflammation leads to lymphedema and thickening of the bowel wall and mesentery. Mesenteric fat typically extends onto the serosal surface of the bowel. Mesenteric lymph nodes often enlarge. Extensive inflammation may result in hypertrophy of the muscularis mucosae, fibrosis, and stricture formation, which can lead to bowel obstruction.
• Abscesses are common, and fistulas often penetrate into adjoining structures, including other loops of bowel, the bladder, or psoas muscle. Fistulas may even extend to the skin of the anterior abdomen or flanks. Independently of intra-abdominal disease activity, perianal fistulas and abscesses occur in 25 to 33% of cases; these complications are frequently the most troublesome aspects of Crohn disease.
• Noncaseating granulomas can occur in lymph nodes, peritoneum, the liver, and all layers of the bowel wall. Although pathognomonic when present, granulomas are not detected in about half of patients with Crohn disease. The presence of granulomas does not seem to be related to the clinical course.
• Segments of diseased bowel are sharply demarcated from adjacent normal bowel (called skip areas), hence the name regional enteritis.
  
  • About 35% of Crohn disease cases involve the ileum alone (ileitis).
  • About 45% involve the ileum and colon (ileocolitis), with a predilection for the right side of the colon.
  • About 20% involve the colon alone (granulomatous colitis), most of which, unlike ulcerative colitis, spares the rectum.

Crohn’s disease causes

• Exact cause of Crohn’s disease remains unknown
• Immune system
  
  • Virus/bacterium triggers Crohn’s disease possible cause
    
    • When immune system tries to fight off the invading microorganism, an abnormal immune response causes the immune system to attack the cells of the digestive tract too
• Heredity
  
  • Higher prevalence in individuals with family members who have Crohn’s disease

Question 49

Malnutrition

Answer 49

Biochemistry of malnutrition

• Metabolic response to starvation is primarily concerned with maintaining a supply of water soluble substrates to supply energy to the brain
• Hence initial rise in metabolic rate, reflecting gluconeogenic activity
• Fasting progresses -> gluconeogenesis is suppressed to minimize muscle protein breakdown and ketones become the main fuel for the brain
• Basal metabolic rate per cell decreases -> slow growth and low adult body size
• Types of malnutrition
  
  • Kwashiorkor (protein malnutrition predominant)
  • Marasmus (deficiency in calorie intake)
  • Marasmic kwashiorkor (marked protein deficiency and marked calorie insufficiency)

Recognising individuals with malnutrition:

• MUST screening tool (malnutrition universal screening tool) – used to identify risk
• Blood tests for screening and monitoring
• Specific tests for iron and vitamins
• Prealbumin tests
• Albumin test -> indicates liver or kidney disease

Risk factors of malnutrition:

• Older adults (especially in hospital or long-term institutional care
• People who are socially isolated (e.g. mobility issues, health problems)
• People with low income
• Recovering from loving with a serious illness/condition
• People who have difficulties absorbing nutrients
• People with chronic eating disorders e.g. bulimia/anorexia nervosa

How can good nutrition improve patient outcomes

• Raising awareness
• Ensuring access to guidance
• Promoting screening and training
• Clarifying standards
• Malnutrition in IBD due to
  
  • Poor appetite
  • Food aversions
  • Malabsorption
  • Increase in calories in body burned to fight the disease and its complications
  • Nutrient losses due to diarrhoea or intestinal bleeding

Question 50

Malnutrition (weight loss)

Answer 50

Weight loss and malnutrition

• Weight loss due to depletion of fat and muscle cells
• Wasting (low weight for height) which can happen as a result of low appetite due to ageing or factors like major surgery, cancer etc
• Stunting (low height for age) or underweight (low weight for age)

Question 51

Peptic ulcer

Answer 51

Peptic ulcer disease risk factors:

• Frequent use of nonsteroidal anti-inflammatory drugs (NSAIDs), a group of common pain relievers that includes ibuprofen
• A family historyof ulcers.
• Illness such as liver, kidney or lung disease.
• Regularly drinking alcohol.
• Stress
• Smoking
• Coffee
• Symptoms*
• Some people with ulcers don’t experience any symptoms. But signs of an ulcer can include:*
• Gnawing or burning pain in your middle or upper stomach between meals or at night.
• Pain that temporarily disappears if you eat something or take an antacid.
• Bloating.
• Heartburn.
• Nausea or vomiting.

In severe cases, symptoms can include:

• Dark or black stool (due to bleeding).
• Vomiting.
• Weight loss.
• Severe pain in your mid- to upper abdomen.

Question 52

Peptic ulcer (GI bleeding differential)

Answer 52

Question 53

Peptic ulcer (diagnosis)

Answer 53

• Investigations*
• Your healthcare provider may be able to make the diagnosis just by talking with you about your symptoms. If you develop an ulcer and you’re not taking NSAIDs, the cause is likely an H. pylori infection. To confirm the diagnosis, you’ll need one of these tests:*
• Endoscopy*
• If you have severe symptoms, your provider may recommend an* upper endoscopy to determine if you have an ulcer. In this procedure, the doctor inserts an endoscope (a small, lighted tube with a tiny camera) through your throat and into your stomach to look for abnormalities.
• H. Pylori tests*
• Tests for H. pylori are now widely used and your provider will tailor treatment to reduce your symptoms and kill the bacteria. A* breath testis the easiest way to discover H. pylori. Your provider can also look for it with a blood or stool test, or by taking a sample during an upper endoscopy.
• Upper gastrointestinal series. Sometimes called a barium swallow, this series of X-rays of your upper digestive system creates images of your esophagus, stomach and small intestine. During the X-ray, you swallow a white liquid (containing barium) that coats your digestive tract and makes an ulcer more visible.*
• Imaging tests*
• Less frequently, imaging tests such as* X-raysand CT scans are used to detect ulcers. You have to drink a specific liquid that coats the digestive tract and makes ulcers more visible to the imaging machines.

Question 54

Peptic ulcer (management)

Answer 54

• Management*
• Treatment for peptic ulcers depends on the cause. Usually treatment will involve killing the H. pylori bacterium if present, eliminating or reducing use of NSAIDs if possible, and helping your ulcer to heal with medication.*
• Medications can include:*
• Antibiotic medications to kill H. pylori. If H. pylori is found in your digestive tract, your doctor may recommend a combination of antibiotics to kill the bacterium. These may include amoxicillin (Amoxil), clarithromycin (Biaxin), metronidazole (Flagyl), tinidazole (Tindamax), tetracycline and levofloxacin.
• The antibiotics used will be determined by where you live and current antibiotic resistance rates. You’ll likely need to take antibiotics for two weeks, as well as additional medications to reduce stomach acid, including a proton pump inhibitor and possibly bismuth subsalicylate (Pepto-Bismol).*
• Medications that block acid production and promote healing. Proton pump inhibitors — also called PPIs — reduce stomach acid by blocking the action of the parts of cells that produce acid. These drugs include the prescription and over-the-counter medications omeprazole (Prilosec), lansoprazole (Prevacid), rabeprazole (Aciphex), esomeprazole (Nexium) and pantoprazole (Protonix).
• Long-term use of proton pump inhibitors, particularly at high doses, may increase your risk of hip, wrist and spine fracture. Ask your doctor whether a calcium supplement may reduce this risk.*
• Medications to reduce acid production. Acid blockers — also called histamine (H-2) blockers — reduce the amount of stomach acid released into your digestive tract, which relieves ulcer pain and encourages healing.
• Available by prescription or over the counter, acid blockers include the medications famotidine (Pepcid AC), cimetidine (Tagamet HB) and nizatidine (Axid AR).*
• Antacids that neutralize stomach acid. Your doctor may include an antacid in your drug regimen. Antacids neutralize existing stomach acid and can provide rapid pain relief. Side effects can include constipation or diarrhea, depending on the main ingredients.
• Antacids can provide symptom relief but generally aren’t used to heal your ulcer.*
• Medications that protect the lining of your stomach and small intestine. In some cases, your doctor may prescribe medications called cytoprotective agents that help protect the tissues that line your stomach and small intestine.
• Options include the prescription medications sucralfate (Carafate) and misoprostol (Cytotec).*

Question 55

Pituitary disorders (Cushing’s)

Answer 55

• Cushing syndrome
  
  • Cushing’s disease (CD) is the result of excess secretion of adrenocorticotropic hormone (ACTH) by a benign monoclonal pituitary adenoma. The excessive secretion of ACTH stimulates secretion of cortisol by the adrenal glands, resulting in supraphysiological levels of circulating cortisol.
  • Clinical state produced by chronic glucocorticoid excess and loss of the normal feedback mechanisms of the hypothalamic-pituitary adrenal axis and loss of circadian rhythm of cortisol secretion
  • Main cause are oral steroids as well as pituitary adenoma
  • Due to HIGH ACTH

Question 56

Pituitary disorders (acromegaly)

Answer 56

Acromegaly

• Excessive growth hormone secretion
• Usually caused by a pituitary adenoma
• Insidious onset and slow progression
• Delayed diagnosis
• Symptoms
  
  • Sweating
  • Change in shoe, ring size
  • Change in facial features
  • Headaches
  • Lethargy
  • Joint pains
  • Galactorrhoea, amenorrhoea
• Signs
  
  • Coarse facial features
  • Macroglossia
  • Deep voice
  • Spade like hands, enlarged feet, OA
  • Carpal tunnel syndrome
  • Goitre and organomegaly
  • UP to ⅓ patients will have symptoms of _hyperprolactinaemia_ due to adenoma also secreting PROLACTIN
• Investigations
  
  • IGF-1
    
    • Prolonged oral glucose tolerance test
    • High levels of glucose should suppress GH release
    • Fails to happen in acromegaly
  • MRI pituitary
    
    • GH release SHOULD be inhibited by glucose
    • Management
  • Medical
    
    • Somatostatin analogues (Octreotide - inhibits GH release)
    • Dopamine agonists (Bromocriptine, cabergoline) → less effective at suppressing GH release
    • GH receptor antagonists (Pegvisomant)
  • Surgical
    
    • Surgical removal of adenoma is the treatment of choice
• Complications
  
  • Hypertension
  • Impaired glucose tolerance and T2DM
  • Obstructive sleep apnoea
  • IHD and heart failure
  • Increased incidence of thyroid and colon cancer (common screening provided)

Question 57

Thyroid disorders (hyperthyroidism)

Answer 57

Pathophysiology of thyroid (disorders)

• Hyperthyroidism
  
  • In hyperthyroidism, serum T3 usually increases more than does T4, probably because of increased secretion of T3 as well as conversion of T4 to T3 in peripheral tissues. In some patients, only T3 is elevated (T3 toxicosis).
  • T3 toxicosis may occur in any of the usual disorders that cause hyperthyroidism, including Graves disease, multinodular goiter, and the autonomously functioning solitary thyroid nodule. If T3 toxicosis is untreated, the patient usually also develops laboratory abnormalities typical of hyperthyroidism (ie, elevated T4 and iodine-123 uptake). The various forms of thyroiditis commonly have a hyperthyroid phase followed by a hypothyroid phase.

Question 58

Thyroid disorders (hypothyroidism)

Answer 58

• Hypothyroidism
• Hypothyroidism can be caused by permanent loss or atrophy of functional thyroid tissue (primary hypothyroidism); insufficient stimulation of a normal thyroid gland as a result of hypothalamic or pituitary disease (secondary hypothyroidism, often accompanied by compensatory thyroid gland enlargement); or a defect in the TSH molecule (control hypothyroidism).
  
  • Causes
    
    • When your thyroid doesn’t produce enough hormones, the balance of chemical reactions in your body can be upset. There can be a number of causes, including autoimmune disease, hyperthyroidism treatments, radiation therapy, thyroid surgery and certain medications.
    • Your thyroid is a small, butterfly-shaped gland situated at the base of the front of your neck, just below your Adam’s apple. Hormones produced by the thyroid gland — triiodothyronine (T3) and thyroxine (T4) — have an enormous impact on your health, affecting all aspects of your metabolism. These hormones also influence the control of vital functions, such as body temperature and heart rate.
    • Hypothyroidism results when the thyroid gland fails to produce enough hormones. Hypothyroidism may be due to a number of factors, including:
      
      • Autoimmune disease. The most common cause of hypothyroidism is an autoimmune disorder known as Hashimoto’s thyroiditis. Autoimmune disorders occur when your immune system produces antibodies that attack your own tissues. Sometimes this process involves your thyroid gland. Scientists aren’t sure why this happens, but it’s likely a combination of factors, such as your genes and an environmental trigger. However it happens, these antibodies affect the thyroid’s ability to produce hormones.
      • Over-response to hyperthyroidism treatment. People who produce too much thyroid hormone (hyperthyroidism) are often treated with radioactive iodine or anti-thyroid medications. The goal of these treatments is to get thyroid function back to normal. But sometimes, correcting hyperthyroidism can end up lowering thyroid hormone production too much, resulting in permanent hypothyroidism.
      • Thyroid surgery. Removing all or a large portion of your thyroid gland can diminish or halt hormone production. In that case, you’ll need to take thyroid hormone for life.
      • Radiation therapy. Radiation used to treat cancers of the head and neck can affect your thyroid gland and may lead to hypothyroidism.
      • Medications. A number of medications can contribute to hypothyroidism. One such medication is lithium, which is used to treat certain psychiatric disorders. If you’re taking medication, ask your doctor about its effect on your thyroid gland.
    • Less often, hypothyroidism may result from one of the following:
      
      • Congenital disease. Some babies are born with a defective thyroid gland or no thyroid gland. In most cases, the thyroid gland didn’t develop normally for unknown reasons, but some children have an inherited form of the disorder. Often, infants with congenital hypothyroidism appear normal at birth. That’s one reason why most states now require newborn thyroid screening.
      • Pituitary disorder. A relatively rare cause of hypothyroidism is the failure of the pituitary gland to produce enough thyroid-stimulating hormone (TSH) — usually because of a benign tumor of the pituitary gland.

Pregnancy. Some women develop hypothyroidism during or after pregnancy (postpartum hypothyroidism), often because they produce antibodies to their own thyroid gland. Left untreated, hypothyroidism increases the risk of miscarriage, premature delivery and preeclampsia — a condition that causes a significant rise in a woman’s blood pressure during the last three months of pregnancy. It can also seriously affect the developing fetus.

Iodine deficiency. The trace mineral iodine — found primarily in seafood, seaweed, plants grown in iodine-rich soil and iodized salt — is essential for the production of thyroid hormones. Too little iodine can lead to hypothyroidism, and too much iodine can worsen hypothyroidism in people who already have the condition. In some parts of the world, iodine deficiency is common, but the addition of iodine to table salt has virtually eliminated this problem in the United States.

Question 59

Abdominal pain (differential diagnosis)

Answer 59

Question 60

Acid base balance (renal failure)

Answer 60

Renal failure Acid base disturbance

• Due to kidney failure it is common to develop metabolic acidosis.
• Kidneys do not remove acid from the body leading to a build-up of acid in the blood
• When bicarbonate levels are low
• The causes of metabolic acidosis:
  
  • Impaired ammonia excretion
  • Decreased tubular reabsorption of bicarbonate
  • Insufficient production of bicarbonate

Question 61

Haematemesis

Answer 61

Haematemesis – vomiting of fresh, red blood and indicates the bleeding in the upper GI tract

Question 62

Haematemesis (GI bleeding)

Answer 62

GI bleeding

• Oesophageal varices
  
  • Most commonly have a history of alcohol abuse
• Gastric ulceration
  
  • Erosion of blood vessels causing a significant hemorrhage
• Mallory-Weiss tear
  
  • Vomiting causes a tear in the epithelial lining of the oesophagus
• Oesophagitis
  
  • Inflammation of the intraluminal epithelial layer of the oesophagus (mostly due to GORD)
• Gastritis
• Gastric malignancy
• Merkel’s diverticulum

Question 63

Haematemesis (diagnosis)

Answer 63

• Blood tests
  
  • FBC (anaemia)
  • U&Es
  • Group and save
  • LFTs (possible liver damage)
  • Coag
  • VBG
• Oesopagogastroduodenoscopy (OGD)
• Erect CXR
  
  • If perforated peptic ulcer is suspected (air visible under the diaphragm)
• CT abdomen with IV contrast
  
  • Good see active bleeding
• Glasgow-Blatchford Bleeding Score
  
  • Urea (mmol/)
  • Hb (g/L)
  • Systolic BP
  • Pulse
  • Melena
  • Syncope
  • Known hepatic failure
  • Cardiac failure

Question 64

Haematemesis (management)

Answer 64

Management

• Do ABCDE assessment
  
  • Insert 2 large bore IV cannulas (& start fluid resuscitation and cross-match blood)
• Peptic ulcer
  
  • Adrenaline
  • High dose intravenous PPI therapy
• Oesophageal varices
  
  • Endoscopic banding
  • Somatostatin analogues/vasopressors (reduce splanchnic blood flow = reduce bleeding)
  • Long term
    
    • Repeated banding of the varices
    • Beta-blocker therapy

Question 65

Haematuria (renal vs urological causes)

Answer 65

Haematuria – presence of blood in urine (visible or non-visible)

Urological causes of haematuria

• Infection (e.g. pyelonephritis, cystitis or prostatitis)
• Malignancy (urothelial carcinoma or prostate adenocarcinoma)
• Renal calculi

Trauma or recent surgery

• Radiation cystitis
• Parasitic (most commonly schistosomiasis)

Question 66

Loose stools (Crohn’s)

Answer 66

Crohn’s link to loose stools

• As affects ileum and large intestine (part where absorbs bile salts ->helps absorb fats) then you get steatorrhea (as unable to absorb fat)
• Cells lining the intestines become inflamed (mucosal inflammation) meaning that the intestines cannot absorb the nutrients and fluid hence, results in loose and watery stools
• Imbalance in electrolyte absorption and/or secretion in the intestine disrupts the osmotic gradient resulting in water retention in the lumen and diarrhoea

Question 67

Loose stools (Coeliac)

Answer 67

Coeliac link to loose stools

• These patients experience inflammation in the small intestine after eaten gluten meaning that the gut lining is damaged and leads to poor nutrient absorption resulting in significant digestive discomfort and frequent diarrhoea/constipation
• It is due to the permanent sensitivity of the intestinal lining to gliadin (which is contained in gluten in wheat and rye) which causes atrophy of the digestive and absorptive cells of the intestine

Question 68

Oedema (nephrotic)

Answer 68

Nephrotic oedema

• 2 models
  
  • Under-fill
    
    • Hypoalbuminaemia reduces capillary oncotic pressure and the imbalance of Starling forces leads to the intestinal leakage of fluid and decreased circulating volume (this then leads to the activation of RAAS)
  • Over-fill
    
    • Say that RAAS and Starling forces are not just to blame but also changes in the endothelial filtration barrier are responsible

Question 69

Oedema (Cushing’s syndrome)

Answer 69

Cushing’s syndrome oedema

• Following surgical treatment of Cushing’s, some patients will continue to experience oedema for some time following surgery due to frequent need for steroid therapy

Question 70

Vomiting (differential diagnosis)

Answer 70

Question 71

Vomiting (peptic ulcer)

Answer 71

Why vomiting in peptic ulcer

• Ulcer pain may be relieved by food, antacids or vomiting
• Vomiting blood (can appear bright red)

Question 72

Weight loss (differential diagnosis)

Answer 72

Differential diagnosis

• Most common aetiologies are:
  
  • Malignancy
    
    • Stomach cancer
    • Colorectal cancer
    • Oesophageal cancer
    • Pancreatic cancer
  • GI conditions
    
    • Coeliac disease
    • Peptic ulcer
    • Crohn’s disease
    • Ulcerative colitis
  • Psychiatric causes
    
    • Dementia
    • Depression
    • Parkinson’s disease
  • Cachexia syndromes associated with organ failure (e.g. heart failure, COPD, renal failure)
  • Endocrinopathies (e.g. hyperthyroidism, diabetes mellitus, adrenal insufficiency)
    
    • Addison’s disease
  • Serious infections (e.g. TB and HIV)
  • Medication side effects
  • Substance abuse
    
    • Alcohol, cocaine
  • Social factors that prevent adequate access to food

Question 73

Weight loss (investigations)

Answer 73

Investigations

• Physical examination & medical history
• Blood tests
  
  • FBC
  • TFT
  • U&Es
  • HbA1c
  • Random glucose
  • CRP
• Urinalysis
• Procedure
  
  • Endoscopy
  • Echocardiogram
• Imaging
  
  • CXR
  • CT
  • MRI
  • PET scan

Question 74

Bowel habit change

Answer 74

Causes of bowel habit changes:

• Acute gastroenteritis
  
  • Inflammation of the GI tract (the stomach and intestine)
• Simple constipation
• Irritable bowel or diverticular disease
• Colonic malignancy
  
  • Adenocarcinoma
  • Carcinoid tumours
  • GI stromal tumours
  • Colorectal lymphoma
• Inflammatory bowel disease
• Maldigestion / malabsorption

Question 75

Bowel habit change (Crohn’s)

Answer 75

Bowel habit changes in Crohn’s

• Frequent diarrhoea (can also cause constipation)
  
  • Some people have diarrhoea 10 to 20 times a day

Question 76

Bowel habit change (Coeliac)

Answer 76

Bowel habit changes in Coeliac

• Diarrhoea, constipation, and smelly faeces
• Pale, loose or greasy stools (steatorrhea)

Question 77

Bowel habit change (investigations)

Answer 77

Investigations of bowel habit changes

• Investigating tests (X-ray, CT scans, ultrasounds)
• Faecal immunochemical testing
• Endoscopy
• Colonoscopy
• Sigmoidoscopy

Question 78

Bowel habit change (GI bleeding)

Answer 78

GI bleeding link to bowel habit changes

• GI bleeding can mean hemorrhoids, peptic ulcers, tears or inflammation, diverticulosis, diverticulitis, ulcerative colitis, Crohn’s disease, colonic polyps, cancer in colon, stomach or oesophagus
  
  • All these can present with bowel habit changes

Question 79

Lump in the neck (thyroid)

Answer 79

Lump in neck linked to thyroid

• Infective
  
  • Reactive lymphadenopathy (increased size of the cervical lymph nodes in response to infection)
  • Sialadenitis
• Neoplastic
  
  • Lymphoma (haematological malignancy that commonly causes lymphadenopathy)
  • Head and neck cancer
  • Salivary gland tumour
  • Metastatic disease spread
  • Skin lump, ranging from benign (e.g. lipoma) to malignant (skin cancer)
• Vascular
  
  • Carotid body tumour
• Inflammatory
  
  • Sarcoidosis
• Traumatic
  
  • Haematoma
• Autoimmune
  
  • Thyroid disease (e.g. Graves disease)
• Congenital
  
  • Cystic hygroma
  • Thyroglossal cyst
  • Branchial cyst
  • Dermoid cyst

Question 80

Tiredness (Cushing’s syndrome)

Answer 80

Link of Cushing’s syndrome to tiredness

• As there is excess cortisol in the body this causes tiredness
• Also causes the shoulder muscles and thighs/hips to become weaker
• Increased because cortisol is a stress hormone

Question 81

Tiredness (anaemia)

Answer 81

Link of anaemia to tiredness

• Lack of enough healthy red blood cells to carry enough oxygen to the body’s tissues (low haemoglobin making one tired and weak)
• As the cells do not have enough oxygen delivery this means they cannot aerobically respire at such a high rate as they should and hence, they have an increase of lactic acid and toxic waste meaning that one feels fatigued and nauseas

Question 82

Tiredness (hypothyroidism)

Answer 82

Link of hypothyroidism to tiredness

• As there is a decrease in thyroid hormone production
• This is due to lower levels of T3 and T4 in the blood hence
• T3 is important in monitoring the body’s metabolic rate and maintaining bone health

Question 83

Weight gain (hypothyroidism)

Answer 83

Link of weight gain to hypothyroidism

• It is due to excess accumulation of salt and water (rather than stored fats)
• As basal metabolic rate is decreased, an underactive thyroid is associated with weight gain

Question 84

Weight gain (Cushing’s syndrome)

Answer 84

Link of weight gain to Cushing’s syndrome

• Progressive weight gain is the most common symptom of Cushing’s disease
• Usually affects the face, neck, trunk and abdomen more than the limbs
• Increased amount of fat on the upper back and base of the neck
• HIGH levels of cortisol result in the distribution of fat (as high cortisol also makes it hard to lose extra fat