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M4 Y1 > Life Maintenance > Flashcards

Life Maintenance Flashcards

1
Q

List some water soluble micronutrients?

A

Vitamins B & C

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2
Q

What are vitamins used for specifically?

A

Used as cofactors in metabolism

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3
Q

List some fat soluble micronutrients

A

Vits ADEK

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4
Q

How do we calculate total energy expenditure?

A

Total energy expenditure = BMR + diet induced thermogenesis + activity +/- stress (illness/inflammation/surgery)

TEE = BMR + DIT + activity (+stress)

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5
Q

Why do we not use ferritin alone to determine Fe deficiency?

A

Is also an acute phase protein, so concentrations increase during inflammation

This is why we use iron binding studies & do not just rely on one test

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6
Q

What are direct & indirect calorimetry?

A

Direct - measure heat produced by person in sealed chamber

Indirect - estimates heat production by comparing O2 & CO2

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7
Q

What things affect nutrient requirements?

A

Age, gender, body size, level of physical activity, state of health, physiological status (pregnancy & lactation), growth

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8
Q

What are the different dietary reference values?

A

Estimated avg requirement (EAR)
Reference nutrient intake (RNI)
Lower reference nutrient intake (LRNI)
Safe intake (SI)

LRNI & RNI are two SDs from mean in either diection

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9
Q

What is EAR (nutrition)?

A

ESTIMATED AVG REQUIREME
- An estimate of average requirement for energy, or a nutrient
- Approximately 50% of the population will need less & 50% will need more
- EAR is used for energy

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10
Q

What is RNI (nutrition)?

A

Recommended nutrient intake
- Amount of a nutrient that is enough to ensure that needs of nearly all population (97.5%, 2 x standard deviations) are being met
- Many within the group will need less
- Only 2.5% of group will need more
- Often used as a reference amoutn for population groups
- Used for protein, vitamins & minerals

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11
Q

What are some issues with dietary reference values?

A
  • Bioavailability
    • DRVs do take standard (usually low) bioavailability into account, but other things can affect it, e.g. tannin in tea inhibits Fe absorption
  • Assumes that requirements for other nutrients are met
  • Differences in DRVs between countries
  • Based on best available evidence
  • Reflect needs of healthy people only
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12
Q

What are the general causes of nutrient deficiencies, with examples?

A
  • Inadequate intake
    • E.g. Reduced appetite, poor availability of food
  • Reduced absorption
    • E.g. Coeliac disease
  • Increased losses
    • E.g. diarrhoea, vomiting
  • Increased demand
    • E.g. growth, pregnancy
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13
Q

What occurs in severe vitamin A deficiency?

A

Increased risk of infection, xeropthalmia (blinding or non blinding)

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14
Q

Where are cardbohydrates and protein absorbed in the GI tract?

A

Carbohydrates & protein absorption mostly in duodenum & jejunum

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15
Q

Where are fats absorbed in the GI tract?

A

Ileum - fat absorption bound to bile, & fat-soluble minerals

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16
Q

Where in the GI system is vitamin B12 absorbed?

A

In the terminal ileum, bound ti intrinsic factor

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17
Q

Where in the GI system are fluids & potassium absorbed?

A

Ileum & colon

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18
Q

What is the basic structure of the GI tract?

A

Oesophagus - Stomach - Duodenum - Jejunum - Ileum - large intestine - colon

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19
Q

List the main roles of the liver

A

Synthesis, composition & excretion of bile
Synthesis of clotting factors & their actions
Plasma protein production
Metabolism & excretion of bilirubin
Metabolism of carbohydrates, fats, & nitrogen
Drug metabolism
Detoxification

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20
Q

What are the two main types of cell in the liver, and their functions?

A

Hepatocytes (60%) - perform most metabolic functions

Kupffer cells - type of tissue macrophage, clears gut-derived endotoxins from blood

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21
Q

Outline the hepatic lobule

A

Hepatic lobule = functional unit of the liver.

Hexagonal plate of hepatocytes around central hepatic vein.

At each of 6x corners is triad of branches - portal vein, hepatic artery and bile duct (bile duct travels outwards)

https://www.notion.so/Overview-of-the-liver-87a2210eed8b4f9aa3b1c3c9b12da349#aca6502028214d599782ac5de1af5abc

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22
Q

What are the functions of bile?

A

Emulsifies fats to allow absorption
Neutralises gastric juice in S intestine
Eliminates waste products from blood (esp bilirubin & cholesterol)

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23
Q

Outline how bile is secreted

A
  1. Hepatocytes secrete bile salts, cholesterol & others
  2. Epithelial cells lining bile ducts secrete watery solution of Na & HCO3
    (Stimulated by hormone secretin in response to acid in duodenum)
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24
Q

How is bile synthesised?

A

The liver synthesises primary bile acids from cholesterol. Then p.acids conjugated with glycine & taurine (3:1) = bile salts

Bile salts transported against concentration gradient from sinusoidal blood into bile canniculae

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25
Q

What hormone stimulates release of bile from the Gallbladder? What stimulates this hormones release?

A

Cholecystokinin - in response to presence of fat in duodenum

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26
Q

What are the two types of gallstones?

What are some risk factors?

A

Cholesterol (80%)
Pigment (20%)

RFs: High fat diet; inflammation of gallbladder epithelium; women (oestrogen in pregnancy, HRT)

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27
Q

What are the main functions of albumin, and where is it produced?

A

Produced in the liver - as are majority of plasma proteins

Functions - all purpose carrier (fatty acids, hormones, drugs) & is an osmotic regulator

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28
Q

How is haemoglobin broken down?

A
  1. Hb broken down into globin & haem
    • Heme is converted to biliverdin & then free bilirubin, bilirubin bound to albumin & taken to liver
  2. Liver then conjugates it with glucoronic acid
  3. Conjugated bilirubin excreted into bile
  4. Converted by gut bacteria into urobilinogen → 20% reabsorbed, 80% excreted as stercobillinogen → stercobilin

Stercobilin is major metabolite in faeces - brown colour
In urine, yellow urobilinogen

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29
Q

How does the liver control fat metabolism?

A

1) triglycerides oxidised in hepatocytes to produce energy

2) lipoproteins synthesised in liver

3) Excess carbohydrates & proteins are converted into FAs & TGs - stored in adipose

4) Synthesis of cholesterol & phospholipids

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30
Q

How does the liver control nitrogen metabolism?

A

Regulates blood levels of amino acids based on tissues need to protein synthesis

Degrades excess amino acids (mostly in gluconeogenesis)
Transamination of amino acids to non-essential amino acids
Synthesis of urea - removal of ammonia

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31
Q

What key micronutrients are stored in the liver?

A

fat soluble vitamins - ADEK
Stores B12, enough to last 2-3 years
Folate & ferritin

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32
Q

How does the liver remove toxins from the blood?

A
  1. Phase 1 - primary oxidation/reduction - occurs in smooth ER, catalysed primarily by family of cytochrome P450 enzyme - makes substrate into polar compound
  2. Phase 2 - conjugation - makes more water soluble to be eliminated
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33
Q

Outline what occurs in the liver in paracetamol overdose

A

P450 clearance needs glutathione - once this runs out, toxic metabolite NAPQ1 accumulates, binding to hepatic proteins, causes cellular stress, & extensive hepatic necrosis

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34
Q

Outline the clinical features & treatments of a paracetamol overdose, at 0-24h, 24-72h, 72-96h

A

0-24h, preclinical - general malaise, nausea & vomiting, abdo pain, possibly normal LFTs

24-72h, hepatotoxicity - AST & ALT may increase, & bilirubin

72-96h - hepatic failure with encephalopathy - LFT peaks, jaundice, vomiting & GI upset, clinical signs & symptoms of liver faulure, metabolic acidosis

> 96 - multiorgan failure & death

Activated charcoal at 0-4h, NAC after 8h

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35
Q

What happens to alcohol after it is ingested? How can excess alcohol cause damage?

A

Ethanol is broken down in hepatocyte cytosol to acetoaldehyde, which is then converted to acetate by ALDH2. Acetate passes into circulation

Acetoaldehyde causes damage by covalently binding to biomolecules (large scale - hepatitis)

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36
Q

What are some consequences of malnutrition?

A
  • Immune system less functional
  • Impaired wound healing
  • Loss of muscle mass
    • Falls, PUs, chest infection, heart failure
  • Kidneys - over hydration or dehydration
  • Reproduction - reduces fertility
  • Brain - apathy, depression
  • Impaired temperature regulation - hypothermia
  • Micronutrient deficiencies
    • Anaemia, rickets, scurvy, night blindness
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37
Q

How are patients screened for malnutrition?

A
  • Malnutrition universal screening tool (MUST)
    • BMI score + weight loss score + acute disease effect score
  • Subjective global assessment (SGA)
    • Used by Drs rather than nurses
    • More detailed, but also subjective
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38
Q

What are some anthropometry options for pts difficult to weigh & speak to?

A

Protein status
- Mid arm muscle circumference (MAMC)
- Hand grip strength

Fat stores
- Waist circumference
- Tricep skinfold thickness

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39
Q

Describe the metabolic response of the body to injury (NUTRITION-wise)

A
  1. EBB/shock (hours)
    - energy reserves mobilised, but body struggles to utilise
    - BMR & body temp decreases
  2. Flow/catabolism (days)
    - breakdown of energy stores
    - Increased BMR & body temp
    - Acute insulin resistance
    - Visceral & SK muscle breakdown
  3. Recover/anabolism (weeks)
    - Building up energy stores
    - Nutritional therapy aims to increase protein synthesis & restore lean body mass
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40
Q

What are the characteristics of acute liver failure?

A
  • Rapid onset
  • Severe liver failure with hepatocyte necrosis
  • Diminished hepatic funct
    • Coagulopathy (INR>1.5)
    • Hepatic encephalopathy
  • No preexisting liver disease
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41
Q

What are the characteristics of chronic liver failure?

A
  • Chronic injury leading to chronic inflammation
  • Extensive fibrosis
    • Fibrosis still reversible to some degree
    • Can still have normal function even in cirrhosis
  • Presence of regenerative nodules
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42
Q

What are the classifications of acute liver failure?

A

Values are time from jaundice to encephalopathy.

Hyperacute - <7days (v high risk of cerebral oedema)
Acute - 8-28 days (high risk)
Subacute - 5-12 weeks (low)

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43
Q

What are some signs of acute liver failure?

A

Hypoglycaemia, lactic acidosis, hyperammonaemia, coagulopathy (all related directly to liver dysfunction)

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44
Q

What are some causes of acute & chronic liver failure?

A

Viral hepatitis - hepatitis ABCE, herpes, CMV, EBV

Autoimmune hepatitis

Wilsons disease (excess copper, genetic)

Drugs
Alcohol

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45
Q

What are the characteristics of hepatic encephalopathy?

A
  • Brain dysfunction/altered mentation (mental activity)
  • Caused by liver insufficiency (or portosystemic shunting)
  • Spectrum of neurological & psychiatric manifestations
  • Reversible
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46
Q

What is the mechanism that causes hepatic encephalopathy?

A

(very complex and multifactorial, but…)Increased ammonia main thing → increased astrocyte glutamine → osmotic swelling of astroyctes → brain oedema
- Acute liver failure - Happens over short period, often fatal
- Cirrhosis - longer period, reversible

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47
Q

How does portal hypertension arise from cirrhosis, and what complications can occur?

A

High resistance in liver → portal HT → dilated splanchnic veins
- Problems include thrombosis, splenomegaly, ascites, varices

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48
Q

What are some assessments that can be used for cirrhosis?

A

D’amico classification - prognosis
Child Pugh score - severity
UKELD score - prognosis for transplant

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49
Q

How are oesophageal varices treated?

A

Band ligation during OGD

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50
Q

What are the types of pain?

A

Somatic
- MSK, cutaneous, often well localised

Visceral
- Hollow organs & smooth muscle, usually referred
- Poorly localised
- No dedicated sensory pathway in brain for viscera

Neuropathic
- Pain initiated or caused by a primary lesion or disease in the somatosensory nervous system

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51
Q

What would indicate that abdominal pain is somatic (rather than visceral)?

A
  • Constant, can be sharp & momentary with movement or straining
  • Well localised
  • Unaffected by food, defaecation
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52
Q

What are the three possible diagnoses from an upper GI endoscopy for GORD?

A

Erosive reflux disease 20-30%
NERD 60-70%
Barrett’s 5-10%

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53
Q

What is meant by ‘exaggerated oesophago-bronchial reflex?’

A

Same spinal root for upper GI as lungs & trachea - pain in one can cause response in other, e.g. coughing from heartburn

Fun fact - they used to think this was caused by acid going up and into lungs

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54
Q

How can pH further diagnose non-erosive reflux disease?

A

pH testing can diagnose functional heartburn (50% of time is NERD)

Other 50% is called ‘functional heartburn’ - symptoms but no change in pH

This is either hypersensitive eosophagus or just functional heartburn

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55
Q

What causes and what helps delayed gastric emptying?

A

Often occurs in dysmobility-type dyspepsia.

Pro-kinetic drugs help

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56
Q

How is IBS defined?

A

Rome IV

Recurrent abdominal pain, on avg >1/week in last 3 months, associated with 2+ of following:

  • Related to defacation
  • Associated with a change in frequency of stool
  • Assoc with change in form of stool
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57
Q

How can IBS be classified?

A

IBS-C - with constipation
IBS-M - mixed
IBS-D - with diarrhoea

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58
Q

What are some causes of constipation?

What are the two types?

A

Low fibre diet, medications (e.g. opiates), hypercalcaemia, hypothyroidism

Colonic inertia, or pelvic floor dysnergia (pelvic muscles dont relax with defaecation)

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59
Q

What are some treatments and lifestyle advice for constipation?

A

Osmotic laxatives - macrogol (avoid lactulose, non-soluble)

Stimulant - senna, sodium picosulfate

Stool softeners

Avoid caffeine, fat, lactose, wheat, gas producing foods. Have regular, small meals

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60
Q

What are some causes of fatty liver disease?

A

Obesity, DM, malnutrition

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61
Q

When is a liver tumour likely to be metastatic?

A

In non-cirrhotic liver, 90% of tumours are metastatic

In cirrhotic livers, 90% are primary hepatocellular carcinoma (HCC)

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62
Q

What does high GGT indicate?

A

Increased drug metabolism or biliary obstruction

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63
Q

What does high ALT & ALP indicate?

A

ALT - Liver cell death (>10-fold rise)

ALP - cholestasis (>10 fold rise)

10 fold rise with 3 fold rise of the other

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64
Q

List the cell types found in the anterior pituitary gland, what hormones they produce, and what the functions of the hormones are

A

Gonadotroph → LH & FSH (reproductive control)

Lactotroph → prolactin (+breast milk production)

Somatotroph → GH (+growth)

Corticotroph → ACTH (regulation of adrenal cortex)

Thyrotroph → TSH (thyroid hormone regulation)

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65
Q

What is the location of the pituitary gland?

A

Below brain in the Sella Turnica. In line with eyebrows.

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66
Q

What is the pituitary gland derived from (embryology)?

A

Roof of embryonic oropharynx - Rathke’s pouch

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67
Q

List the cell types found in the posterior pituitary gland, what hormones they produce, and what the functions of the hormones are

A

Trick question - the posterior pituitary does not produce hormones, but stores and releases hypothalmic hormones.

ADH - water control
Oxytoxin - mood & lactation

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67
Q

What are the main syndromes of hormone excess, and what hormone is each associated with?

A

GH - acromegaly
ACTH - Cushings
TSH - secondary thyrotoxicosis
LH/FSH - non functioning tumour
PRL - prolactinoma

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68
Q

What are the main effects of GH excess?

A

Acral enlargement, macroglossia, spade like hands

Increased skin thickness & sweating, + skin tags.

Metabolic changes, including diabetes.

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69
Q

What are the actions of cortisol?

A

⬆️ Plasma glucose levels
- +Gluconeogenesis, +glycogenolysis, +glycogen storage
⬆️ Lipolysis
Proteins are catabolised
Anti-inflammatory
Increased gastric acid production

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70
Q

What are the main effects of cortisol excess?

A

Cushings syndrome

Changes in fat & protein metabolism - change in body shape (central obesity, moon face, buffalo hump), ecchymosis, osteoperosis

Changes in sex hormones (excess hair growth, irregular periods

Na & H2O retention (high BP & fluid retention)

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71
Q

What are the main features of PRL excess? How is it treated?

A

Sexual - infertility, impotence, amenorrhea/oligomenorrhea

Galactorrhea

Treated with a dopamine agonist (inhibits prolactin release)

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72
Q

How are pituitary adenomas treated?

A

Surgery - transsphenoidal
Chemo (slow)
Drugs (block hormone production/release)

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73
Q

What are the main issues with measuring body fat using BMI?

A

Does not distinguish between muscle & fat - we lose muscle mass as we age

Cannot determine where fat is stored (visceral vs subcutaneous)
- Visceral fat (within abdominal cavity surrounding vital organs) strongly associated with chronic disease risk

Associations between obesity & health risks are different in older populations (older populations being overweight =/= risk of mortality (but does for obesity))

Differs for ethnic groups

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74
Q

How can you differentiate between acid-peptic pain & intestinal pain?

A

Acid-peptic - burning or dull (mild or moderately severe)
Intestinal pain - colicky, very severe

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75
Q

What symptoms are associated with biliary issues?

A

Dark urine, pale stools, jaundice

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76
Q

List some causes of upper abdominal pain

A

GORD, functional dyspepsia, ulcer, cancer, cholelithiasis, pancreatitis, IBS, more

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77
Q

What are some exacerbating factors of - GORD, peptic ulcer, IBS respectively

A

GORD - food & drink, lying down, bending over

Peptic ulcer - nocturnal, worse on hunger, improved by food & antacids

IBS - pain gives urge to defacate, relieved by defacation

78
Q

What would you look for in a patient with gastro symptoms (with no alarm symptoms?)

A

H. Pylori

79
Q

What initial investigations should be carried out for a patient experiencing dyspepsia?

A

FBC, LFT, ECG
Medication review
H. Pylori stool sample

80
Q

What are the indications for an upper GI endoscopy?

A

To be performed within two weeks if:

Dysphagia OR aged 55+ with weight loss & any of the following:

  • Upper abdo pain
  • Reflux
  • Dyspepsia
81
Q

How is oesophagitis classified?

A

Using LA classification, gives grade 1-4

82
Q

When is the best time to take PPIs?

A

With a meal!

83
Q

What are ‘alarm’ symptoms for GI?

A

Anorexia, weight loss, persistent vomiting, anaemia, haematemesis & malaena, abdominal mass.

84
Q

What treatments for GORD?

A

Lifestyle - Weight loss, elevation of head, smoking, set meal times & small meals, no food 3h before bed. Avoid caffeine
Medical - antacids, alginates, H2RA, PPI, prokinetics
Surgical - fundoplication

85
Q

What is the blood supply of the thyroid? What does that vessel arise

A

Inferior thyroid artery from subclavian

Superior thyroid artery from carotid

86
Q

What central & peripheral hormones are involved with the thyroid?

A

Peripheral - T3 & T4 (thyroxine)

TRH from hypothalamus -> pituitary
TSH from pit. -> thyroid

87
Q

a) What are the actions of thyrotophin?

b) Where is it produced?

A

b) Produced by thyrotroph cells of the anterior pituitary

a) Act on GPCRs on the thyroid follicular cell to:
- Increase thyroid iodine uptake & colloid production
- Thyroid hormone secretion
- Increase thyrotroph growth

88
Q

How is T3&4 transported around the body? What are their half lives?

A

Circulate bound to protein - thyroid-binding globulin, albumin, prealbumin.

Half lives:
T3 - 1-3 days
T4 - 4-7 days

89
Q

What is required in the diet for thyroid hormone production? Where do we get this?

A

Iodine. Get from salt water, landlocked populations are more likely to have deficiency.

90
Q

What specifically do thyroid hormones bind to? What actions does this have?

A

Type 2 nuclear receptor, which induces gene transcription.

Actions:
- Increases metabolic rate
- Increases thermogenesis
- Increases sympathetic nerve activity
- Increase protein synthesis
- Chronotropic

91
Q

List some causes of hypERthyroidism

A
  • Graves disease
  • Multinodular goitre
  • Toxic solitary nodule
  • Thyroiditis
  • Iodine excess
92
Q

What investigations would be suitable for suspected hyperthyroidism?

A
  • Thyroid function
  • Autoantibodies
  • Technesium scanning
  • ESR (erythrocyte sedimentation rate)
93
Q

What is Grave’s disease?

A

Autoimmune condition mediated by anti-TSH-receptor autoantibodies
- Antibodies bind to TSH receptors on thyroid → T3&4 release

94
Q

What are the symptoms of graves disease?

A

Chemosis - oedema under conjunctiva & blood vessels engorged

Proctosis - eye pushed forward (antibody that attacks thyroid also attacks muscles at back of eye)

Pretibial Myxodema - swelling on shins, ulceration

Acropachy - sausage fingers

95
Q

What are some symptoms of hyperthyroidism?

A
  • Sympathetic activation (Tachycardia, palpitation, agitation, increased locomotor activity, weight loss, Heat intolerance → fever)
  • Poor appetite
  • Myopathy
  • Children - increased growth & precoscious puberty
  • Elderly - minimal symptoms
  • Diarrhoea
96
Q

What is goitre? Cause?

A

Swelling of the thyroid gland, caused by iodine deficiency (get from sea salt).

Can be smooth or multinodular

97
Q

What are the treatment options for thyrotoxicosis?

A

Carbimazole (thionamide) reduces thyroid function

Propylthiouracil

Beta blockers - sympathetic symptoms, (carbimazole takes 6-8 weeks to work. CCBs if BBs not enough)

Radiotherapy - radioactive iodine

Surgery - subtotal thyroidectomy

98
Q

a) What does thyroiditis cause

b) How is it treated?

c) How is it investigated?

A

a) Causes hypERthyroidism.

b) BBs usually sufficient to control symptoms, as usually resolves spontaneously

c) High ESR, technesium scan will show no uptake

99
Q

What are Howell-Jolly bodies?

A

Remnants of RBC nuclei that are normally removed by the spleen

100
Q

Where is iron found in the body?

A

Plasma transferrin - 3mg

Intracellular (ferrititin):
Liver (1000mg) in Kuppfer cells
Bone marrow (300mg)

Reticuloendothelial macrophages (600mg)
Circulating RBCs (1800mg)
Muscle myoglobin - 300mg

101
Q

Where is iron absorbed (& by what receptor)?

What effects absorption of Fe?

A

Max absorption in duodenum & proximal jejunum via ferroportin receptors.

Absorption affected by Fe form (haem = ferrous(meat), non-haem = ferric), GI acidity, state of iron storage levels & bone marrow activity

102
Q

What would you expect iron studies to show in iron deficiency anaemia

A

Serum Fe - varies hugely throughout day, dont look at it

Ferritin - low
Transferrin - high (trying to compensate)
Transferrin sat - low

103
Q

What is total iron binding capacity?

How would anaemia of chronic disease affect it?

What is the main regulator of TIBC?

A

An indirect measure of transferrin. ACD would make TIBC low, as aim is to reduce iron availability for pathogens.

Transferrin is regulated by hepcidin

104
Q

What are some causes of macroyctic anaemia?

A

Megaloblastic:
Vitamin B12/folate deficiency
Drug-related (interferes with B12/FA metabolism)

Non-megaloblastic:
Hypothyroidism, liver disease, alcoholism, reticulocytosis (haemolysis)
Myelodysplastic syndromes

105
Q

Why do we need folate, where is it absorbed, & what foods give us it?

A

Absorbed in Jejunum.

Needed for DNA synthesis (A,G&T synthesis)

Dietary sources - dark leafy veg, fruit nuts & beans, dairy poultry meat fish eggs.
60-90% lost in cooking!

106
Q

What are some causes of B12 & folic acid deficiency?

A

B12 - ileal resection, vegan diet, malnutrition, intrinsic factor receptor defiency, alcohol, parasites, pernicious anaemia

Folic acid - poor diet, elderly, chronic alcohol intake, SCD (or other cause of rapid RBC turnover), jejunal resection, coeliac

Pregnancy, growth spurts can cause both

107
Q

What is pernicious anaemia?

A

Autoimmune disorder
- Gastric parietel cell & IF antibodies
- Lack of IF → lack of B12 absorption

108
Q

What are the four main causes/types of diarrhoea

A

Osmotic - non-absorbable solute, draws water into colon

Exudative - intestinal mucosal damage (e.g. infections, IBD, coeliac)

Secretory - impaired electrolyte transports (e.g. laxatives, bile salts, bacterial endotoxins)

Motility - increased transit (e.g. IBS, drugs, DM, thyrotoxicosis)

109
Q

What is IBS, & how is it diagnosed?

A

Defined as a functional GI disorder, classified by GI symptoms, relating to any combination of the following
- Motility disturbance
- Visceral hypersensitivity
- Altered mucosal & immune function
- Altered gut microbiota
- Altered CNS processing

Diagnosed by ROME IV criteria - Recurrent abdominal pain, on avg >1 day/week in last 3 months, associated with 2+ of following:
- Related to defecation
- Associated with a change in frequency of stool
- Associated with a change in form of stool

110
Q

How is IBS managed?

A
  • Investigations & reassurance (to confirm diagnosis)
  • Diet & lifestyle advice
  • Medications for symptom relief
    • Anti spasmodics
      • Mebeverine
      • Peppermint oil
    • Drugs to alter intestinal transit
      • Opiates
      • Laxatives
    • Probiotics
    • Anti-depressants
111
Q

What is coeliac disease?

A

‘an inflammatory condition of the small intestinal mucosa, that is most marked proximally, and which improves morphologically when gluten is removed from the diet’

Inherited autoimmune condition strongly associated with HLA-DQ2 genotype

112
Q

How does coeliac disease present in adults & children, respectively?

A

Children - failure to thrive, diarrhoea, vomiting

Adults - fatigue & anaemia main signs. High RDW & macro or microcytic anaemia

113
Q

How is coeliac disease diagnosed?

A

4 intestinal biopsies taken. Abnormal mucosa shown on exposure to gluten, and improvement shown from gluten free diet (after 3-6 months)

114
Q

What are some causes of hypothyroidism?

A

Congenital - Pendred’s syndrome, congenital hypothyroidism

  • Iodine deficiency
  • Hashimoto’s thyroiditis
    • Autoimmune antibodies
  • Gland destruction
115
Q

How would hypothyroidism be investigated?

A

Thyroid function, autoantibodies (thyroid peroxidase antobody = Hashimotos), ultrasound if goitre present

116
Q

How should a thyroid swelling be investigated?

A

Thyroid function, ultrasound, CT/MRI

If nodules & not goitre, fine-needle aspiration

If goitre, CXR & flow volume loop (?extrathoracic compression of airways)

117
Q

A 39-year-old-woman presents with weight gain, lethargy, headaches and constipation. She is 10 weeks post partum. Examination of the neck is normal but she is found to have papilloedema. Her investigations reveal.

TSH mU/L [0.3-3.2] <0.05 fT4 pmol/l [9-26]4.2 fT3 pmol/l [2.5-5.7]0.8

The most likely diagnosis is:
A) Secondary hyperthyroidism
B) Primary hyperthyroidism
C) Primary hyperparathyroidism
D) Secondary hypothyroidism
E) Primary hypothyroidism

A

D, as no TSH is being produced. Would be primary if TSH was high & T3/4 still low, as problem would be thyroid gland not pituitary

118
Q

A 42-year-old-woman presents with weight gain, lethargy, headaches and constipation. Examination of the neck reveals a smooth goitre.

Her investigations reveal: TSH mU/L [0.3-3.2] 50 fT4 pmol/l [9-26]6.2 fT3 pmol/l [2.5-5.7]1.8

The most likely diagnosis is

A) Secondary hyperthyroidism
B) Primary hyperthyroidism
C) Primary hyperparathyroidism
D) Secondary hypothyroidism
E) Primary hypothyroidism

A

E - primary as problem lies in thyroid

119
Q

A 26-year-old-man presents with weight loss, supraventricular tachycardia, headaches and diarrhoea. Examination of the neck is reveals a smooth goitre. Examination of the eyes reveals exophthalmos of the left eye and bilateral lid lag

Her investigations reveal: TSH mU/L [0.3-3.2] <0.05 fT4 pmol/l [9-26] 86.2 fT3 pmol/l [2.5-5.7]11.8. TSH receptor antibody 16 [<6] Thyroid peroxidase (TPO) antibody 25 [<35]

The most likely diagnosis is:
A) De Quervain’s Thyroiditis
B) Primary hyperthyroidism
C) Graves Disease
D) Secondary hyperthyroidism
E) Hashimoto’s Thyroiditis

A

C

120
Q

What is ulcerative collitis? Give an overview

A

Chronic inflammatory disease of unknown aetiology, only affects colon

Diarrhoea with blood and mucus

Systemic features if extensive and/or severe

Exacerbations and remissions

15-20% of attacks are ‘severe’

121
Q

Where do Ulcerative collitis & Crohns affect the body, respectively?

A

Ulcerative collitis - colon, either proctitis (just rectum), left-sided colitis (descending colon & rectum) or pancolitis (all of colon)

Crohns - can happen anywhere in digestive system, usually S intestine or ascending/right colon

122
Q

What artery supplies the ileum, and where does this arise from?

A

Superior mesenteric artery; arises from descending aorta at L1

123
Q

What are the main anatomical differences between the jejunum & ileum?

A

Jejunum - wider lumen, thicker walled & denser plicae circulares (folds)

Jejunum has greater blood supply, with fewer arterial arcades & long vasa recta

Jejunum mesentery contains less fat than ileum, so appears more

124
Q

Describe arterial supply and innervation of the transverse colon

A

Arterial supply:
- midgut - superior mesenteric
- Distal part (hindgut) - inferior mesenteric

Innervation:
Parasympathetic -
- Midgut - vagus nerve
- Hindgut - pelvic splanchnic nerve (S2-S4)
Sympathetic - lesser splanchnic to lumbar splanchnic

125
Q

What is the function of the PCT of the nephron? How does this affect cell contents?

A

Majority of reabsorption - 65% of water
High energy consuption & O2 demand, lots of mitochondria

126
Q

What is the function of the LOH of the nephron? How does this affect cell contents?

A

Descending loop - Permeable to water.
Cells flat with less mitochondria.

Ascending loop - reabsorption of electrolytes out of tubule
Cells thicker with mitochondria

Counter-current mechanism here

127
Q

What is the function of the DCT of the nephron? How does this affect cell contents?

A

More reabsorption of electrolytes & water.
Tall cells with numerous mitochondria.

127
Q

What is the function of the collecting duct of the nephron? How does this affect cell contents?

A

Responsible for water absorption. Two major cell types

  • Principal cells - Na reabsorption & vasopressin action
  • Intercalated cells - responsible for acid secretion
128
Q

What main solutes are reabsorbed in the nephron, and where?

A

PCT - Glucose, HCO3, Na, Cl, Ca
TALH & DCT & collecting duct - Na & Cl

129
Q

What are some key transport proteins in the nephron, their function & locations?

A
  • Na-glucose co transporter - Na & Gluc reabsorption (PCT)
  • Na-H exchanger (PCT & TALH)
  • Na-CL co-transporter - DCT
129
Q

Nephron - what are the main transporters involved in sodium reabsorption? What are their locations & % of Na absorption?

A

Na-H exchanger - PCT, 65%
Na-2Cl-K - TALH, 25%
Na-Cl cotransporter - DCT, 5%
Epithelial Na channel - collecting duct, 5%

130
Q

Draw out how sodium is reabsorbed in the proximal tubule.

A

Na/H exchanger brings Na in from lumen, into cells, which is then passed into blood via Na/K exchanger

H in the lumen combines with a base to form carbonate ions.

These carbonate ions are converted to CO2 & H2O by carbonic anhydrase

131
Q

Draw out how sodium is reabsorbed in the TALH.

A

Na-2Cl-K channel from tubular lumen to cell

Passed on to intersitial fluid (& blood) by KCl co transporter, & K & Cl channels

132
Q

Draw out how sodium is reabsorbed in the DCT.

A

Epithelial Na-K channel drives concentration gradient, allowing passive Na absorption from tubule

133
Q

How is water reabsorbed in the nephron, what stimulates this, and what is the usual volume reabsorbed?

A

Via aquaporins, stimulated by vasopressin/ADH. 180L filtered by kidneys, 2.4L urine normal = ~177L reabsorbed.

134
Q

What is tubulo-glomerular feedback?

A

Increased salt & water at distal tubule causes afferent aftery vasoconstriction -> Decreased filtration pressure & GFR

135
Q

How does the counter-current system of the nephron LOH work?

A

The osmotically active molecules [Na,Cl,K] are pumped out from the ascending limb of loop of Henle generating hyperosmolar medulla which drives water out along osmotic gradient in descending limb. Urea is pumped out by UT A1 UT A3 from CD stimulated by ADH

136
Q

List some main diuretics & where they act

A

Loop diuretics - work at loop of Henle (E.g. furosemide)

Thiazide diuretics - work at DCT

K-sparing - work at collecting duct (e.g. Spironolactone, inhibits aldosterone)

137
Q

List the main functions of the kidneys

A
  • Maintains ECF volume
  • Osmotic pressure balance
  • Electrolytes balance
  • Acid-base balance
  • Filtration of plasma
  • Mineral metabolism
  • Production of EPO -> red cell production
  • Gluconeogenesis
138
Q

What are the main layers of the glomerulus?What is the function of the glomerulus?

A

(In->out) Endothelium, basement membrane, podocytes

Podocytes act as a filter, preventing plasma proteins from being excreted.

Glomerulus filters all

139
Q

List the main NTs that effect the kidneys, and their effects on renal blood flow

A

NA - constriction
Dopamine - dilation
Angiotensin II - constriction

140
Q

What is meant by autoregulation of glomerular blood flow? How is it achieved?

A

Myogenic reflex:
The glomerulus can autoregulate its blood supply in response to systemic blood pressure changes to preserve the filtration pressure.

Constriction achieved by inhibition of prostaglandin & stimulation of sympathetic NS

80-210 SBP, kidneys will be fine!

141
Q

How is renal blood flow measured, in theory?

A

Ficks principle - measuring the amount of filtered substance per unit time divided by the difference in concentration between the renal artery and vein

Substance used is P-amino hippuric acid (PAH). 90% is removed in single pass.

142
Q

What are the main buffers of the body?
Give chemical equations, not overall systems.

A

Blood:
H2CO3 <> H+ + CO3-
HProt <> H+ + Prot-
HHb <>H+ + Hb-

Interstitial fluid:
H2CO3 <> H+ + HCO3-

Intracellular:
HProt <> H+ + Prot-
H2PO4- <> H+ + HPO4(2-)

143
Q

How is urea produced?

A

In the liver, oxidative deamination of amino acids produce ammonia & keto acids.

Urea is formed from ammonia with CO2

144
Q

How does the nephron help maintain acid-base balance?

A

Proximal tubule
- Reabsorbs makority of filtered bicarbonate
- Produces & secretes ammonium

TAHL
- Reabsorbs filtered bicarb

Distal tubule & collecting duct
- Type A intercalated cells
- Reabsorbs remaining filtered bicarb
- Acidifies tubular fluid
- Type B intercalated cells
- Secretes bicarbonate
- Non-intercalated & type A
- Secretes ammonia & ammonium

145
Q

What is the mechanism of bicarbonate reabsorption in the PCT of nephrons?

A

In the lumen filtered bicarbonate combines with H+ to form CO2 and water (CAH)

CO2 diffuses into the cell

In the tubular cell CO2 combines with water to form H2CO3 (CAH again)

H2CO3 breaks into H+ which is excreted with Na/H exchanger

HCO3 moves into interstitium

Na is pumped into the interstitium

146
Q

What is the mechanism of bicarbonate reabsorption in the distal tubule (distal DCT & collecting duct)

A

H+ generated from H2O and CO2 is actively pumped out in lumen

H+ in the lumen combines with HPO42-

147
Q

What is the mechanism of ammonia secretion in the distal tubule (distal DCT & collecting duct)

A

Ammonia is generated from Glutamate

NH4+ breaks into H+ and NH3

NH3 diffuses out into lumen
NH3 combines with H+

NH4+ is excreted in urine

148
Q

Describe the physiological response to a drop in BP

A

Detection by baroreceptors in carotid body -> ADH release from p.pituitary -> thirst & H2O/Na retention in collecting duct

Drop in BP in juxtaglomerular apparatus -> renin release -> Angiotensin II causes vasoconstriction & aldosterone release
Aldosterone -> Na reabsorption in DCT & collecting tubule (& therefore water reabsorption)

149
Q

How is GFR measured in clinical practice?

A

Creatinine, with age & weight

150
Q

What is CKD?

A

The presence of either kidney damage or decreased kidney function for three or more months, irrespective of cause.

151
Q

What are some RFs for CKD?

A

Diabetes, HTN, CVD, obesity, smoking, proteinuria, NSAIDs, certain ethnicities

152
Q

How is CKD risk assessed?
Who should be assessed?

A

Urine albumin (main one) & GFR

ACR used - albumin:creatinine ratio (higher = more severe)
Detected by urine dip

Assessment of CKD should be done in anyone with diabetes, HTN, CVD, AKI or a family history

153
Q

How does diabetes lead to an increased risk of CKD?

A

Increased reabsorption of glucose via SGLT2 (PCT, absorbs glucose & Na together) reduces Na delivery at macula densa

Resulting tubuloglomerular feedback dilates afferent arteriole & increase glomerular perfusion

High angiotensin II (renin released due to +plasma osmolality) induces efferent arteriole vasoconstriction

→ high interglomerular pressure & hyperfiltration
- →inflammation, RAAS activation & oxidative stress

154
Q

How is CKD managed?

A

Glucose & BP control

ACEi or ARB (albuminuria)

Statins

155
Q

What are some causes of pre-renal AKI?

A

Hypovolaemia, hypotension, renal hypoperfusion or vasoconstriction (NSAIDs, ACEi, ARB)

156
Q

What are some indications for acute dialysis?

A

Hyperkalaemia refractory to medical therapy; severe acidosis, fluid overload, symptomatic uraemia

157
Q

What are the main complications of declining GFR & end stage renal failure?

A

Haematological issues (anaemia - iron not absorbed)
Bone issues (phosphate not reabsorbed), CVS complications,

158
Q

Describe how DKA occurs

A

Usually T1DM (may be T2)

No insulin production signals starvation mode - catabolic hormones secreted (glucagon, catecholamines, cortisol & GH)

Unable to get glucose into cells (insulin required), so unable to metabolise glucose. Ketone bodies are rapidly produced from lipolysis in liver as a result, causing acidosis

plus XS glycogenesis (hence removal of oxaloacetate, substrate for TCA)

159
Q

How does osmotic diuresis occur? What happens as a result?

A

(Diabetes) Hyperglycaemia -> Glycosuria causes osmotic diuresis by drawing water into urine.

Causes dehydration, huge loss of water (5-8L) & electrolyte loss.

Fluid resus required

160
Q

How is DKA managed?

A

Insulin to resolve ketone production (with glucose if sugar drops rapidly)

Metabolic correction, fluid resuscitation & ongoing management.

Identify any potential causes e.g. infection or MI

161
Q

What is a hyperglycaemic hyperosmolar state?

A

Marked hyperglycaemia (>30mmol/l), without significant ketosis nor acidosis. There is dehydration with some depression of consciousness (high blood viscosity & poor nutrient delivery to brain (hyperosmolar))

Occurs in T2DM

162
Q

What are the clinical features of hyperosmolar hyperglycaemic state?

A

Elderly, confused, vomiting, dehydration, pyrexia, focal neurology

Stroke like-symptoms due to effect on brain

Coma

High glucose but normal pH

163
Q

List the main complications that can occur in diabetes, both acute & chronic.

A

Acute (metabolic) - DKA & HHS

Chronic - microvascular (retinopathy (proliferative or non-proliferative), nephro- neuro-pathy)
Macrovascular - atheromas -> HTN, CHD, stroke, peripheral vascular issues

164
Q

Describe how glycation products can form as a result of diabetes?

What effects do glycation products have?

Flow diagram may help!

A

All within a cell:
High glucose causes an increase in ROS, cleanup of which produces GAPDH - this prevents glucose from entering Krebs cycle

Glucose enters other metabolic pathways as a result, disrupting cellular metabolism.

The products of these pathways cause protein modification, eventually leading to amadori products (e.g. HbA1C)

Overall effects are increased vascular permeability, vasoactive hormone synthesis & basement membrane synthesis.

Oxidative stress as a result - vasoconstriction, inflammation & thrombosis

165
Q

Diabetic nephropathy - what risk factors are associated, and how is it assessed?

A

RFs - early age of DM onset, duration with DM, men, poor glycaemic control, BP & smoking

Assessment - ACR - microalbuminurea shows early stage, still preventable.
Macroalbuminurea, (+ve on dipstick) shows later irreversible stage

166
Q

Describe the progression of diabetic nephropathy

A

15-20years - hyperfiltration, micro then macro albuminurea.

Renal failure over 4-5 years then ESRF 1 year on

167
Q

How is diabetic nephropathy treated/prevented?

A

ACEis once renal disease present, early on

Tight BM & BP control
Low protein diet & lipid control

168
Q

How are diabetic foot-related issues prevented?

A

Annual checkup with a 10g monofilament to check if pt can feel it - once they cannot, daily pt self-footcare essential.

Also check proprioception with a tuning fork

169
Q

What is autonomic neuropathy?

A

Rare complication of diabetes, occuring after 15-20 years of poor control.

Results in diabetic diarrhoea, sweating when eating, delayed stomach emptying, low blood pressure, erectile dysfunction.

Erectile dysfunction is an important indicator - occurs ~3y before first cardiac event

170
Q

What are the main macrovascular complications of diabetes?

A

CHD (RRx2-4)

Cerebrovascular disease (RRx2-4)

Peripheral vascular disease - leading cause of non-traumatic amputations

171
Q

What are the main differences between neuropathic and ischaemic foot in a diabetic pt

A

Neuropathic foot - sensory defect, pulse present, cocked toes, excess callus formation at pressure points

Ischaemic - sensory defect MAYBE, pulse absent, structure retained. Ulceration but not at pressure points.

172
Q

Why are diabetic patients predisposed to develop CVD & CHD?

A

Low HDL, hyperlipidaemia, raised VLDL, plus more genetic factors lead to increased atheroma formation.

Diabetic pt has a RR of 2-4 x that of a non-diabetic individual

173
Q

How should diabetic pts be managed? (overall)

A

Advice
BP control
Cholesterol
Diabetic control
Eye care
Foot care
Guardian drugs

174
Q

What are the main effects of insulin?

A

Stimulate nutrient storage - uptake of glucose by tissues, glycogen synthesis in liver & skeletal muscle; uptake of FA & AA

Inhibit nutrient release - inhibits hepatic glycogenolysis; inhibits proteolysis & lipolysis

175
Q

What are the main counter-regulatory hormones of metabolism, and their effects?

A

Glucagon - stimulates hepatic glycogenolysis

Adrenaline - hepatic glycogenolysis, lipolysis & release of FA from adipose

GH - same as above

Cortisol - same as above AND proteolysis

176
Q

How is glucose taken up and released from adipose tissue?

A

Enters cells by insulin-dependent GLUT4 channel protein

Converted to FA in presence of insulin, & glycerol

FA & glycerol form triglycerides - main constituent of adipose

In presence of NA/A -> FA & glycerol which leave cell

177
Q

Describe the short term response to hypoglycaemia in a healthy individual

A

Immediate detection by pancreas, glucagon secretion increased from alpha cells

Brainstem & hypothalamus detects low BG -> sympathetic stimulation (glycogenolysis & Adrenaline release)

178
Q

What are the medium and long term effects of hypoglycaemia?

A

Medium term - ketogenesis, retaining glucose levels for essential functions.
Occurs once liver glycogen stores run out (~12h)

Long term - cortisol stimulates proteolysis

179
Q

How does obesity cause hypertension?

A

Insulin resistance & hyperinsulinaemia -> activation of the sympathetic NS

Increase in vasoconstriction, CO & Na reabsorption

Results in HTN

180
Q

What is a medication (& it’s MOA) used in practice for obesity?

Any side effects?

A

Orlistat

Pancreatic lipase inhibitor - causes fat malabsorption.

GI adverse effects & fat soluble vitamin deficiencies.

181
Q

What is dapigaflozin & how does it work?

A

Novel insulin-independent way of removing excess glucose.

Inhibits SGLT2 in PCT

182
Q

What are the main ways in which glucose crosses cell membranes?

A

Na-glucose transporters (secondary active transport):
SGLT1 - gut absorption
SGLT2 - glucose reabsorption in kidney PCT

GLUT transporters:
- GLUT1 (brain, erythrocytes) - high affinity, constant uptake
- GLUT2 (liver, kidney, pancreas, gut) - low affinity, glucose dependent
- GLUT3 (brain) - high affinity
- GLUT4 (muscle & adipose) - medium affinity, insulin dependent

183
Q

Which pancreatic cells secrete which hoemones?

A

A - glucagon
B - insulin
D - somatostatin

184
Q

What is the best way of measuring insulin levels in an individual?

A

C peptide, as it is not metabolised in the liver as insulin is.

C-peptide is produced in the formation of insulin from proinsulin

185
Q

How do pancreatic beta cells detect a rise in glucose?

A
  • Glucose enters cell via GLUT2, is oxidised to ATP, which act as a messenger, closing K channel
    • Decreasing outward K current → depolarises cell
      • VGCCs open → exocytosis of insulin-rich secretory granules

GLUT2 is thought of as the sensor, but is not a receptor

186
Q

What normally occurs when insulin binds to its receptors?

A

Activates protein activation cascades, including:
- Translocation of GLUT4 transporter to plasma membrane
- Glycogen synthesis
- FA synthesis
- Glycolysis

187
Q

What normally occurs when glucagon binds to its receptors?

A

GPCR mechanism activating PKA, which phosphorylates certain substances

Insulin leads to dephosphorylation of same enzymes

188
Q

a) How is diabetes diagnosed?

b) What causes impaired fasting glucose in DM?

A

a) Random plasma glucose >11, fasting glucose >7, oral glucose tolerance test >11.1 (75g glucose drink)

b) Lack of inhibition of glycogenolysis

189
Q

What is the MOA for metformin?

A

Increases sensitivity to insulin:
- Increases kinase activity of insulin receptor
- Inc translocation of GLUT4 transporter

Also decreases FA oxidation & hepatic glucose output

190
Q

What is the MOA for sulfonylureas?

A

In pancreatic beta cells - blocks K-ATP channels (normally blocked by presence of glucose)

This causes depolarisation -> release of insulin

191
Q

What is the MOA of SGLT2 inhibitors?

A

Decreases glucose reabsorption & increases excretion.

Causes osmotic diuresis

M4 Y1 (6 decks)

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