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Case 5 > Case 5 > Flashcards

Case 5 Flashcards

1
Q

What are the 3 features of adaptive immunity?

A
  1. Memory
  2. Specificity
  3. Discrimination of self vs. non-self
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2
Q

What are the 3 types of lymphocytes?

A
  1. T Lymphocytes
  2. B Lymphocytes (provide humoral immunity, resistance against extracellular pathogens and produce specific antibodies)
  3. Natural Killer cytotoxic cells
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3
Q

What is the location of lymphocyte production?

A

Both initially made in the bone marrow
B-lymphocytes: educated and matured in the bone marrow
T Lymphocytes: educated and matured in the thymus

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4
Q

What are the 4 stages of Adaptive immunity?

A
  1. Inflammation
  2. Phagocytosis
  3. T-helper cell activation and clonal expansion
  4. B lymphocyte activation, clonal expansion and clonal differentiation into plasma cells i.e. Ab production
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5
Q

Phagocytosis during adaptive immunity

  • What do neutrophils activate?
  • What do macrophages activate?
  • What do T lymphocytes activate?
A
  1. Neutrophils: cause B lymphocyte activation
  2. Macrophages cause T-helper (CD4) activation
  3. T lymphocyte (CD4) activation
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6
Q

What are the 2 MHC protein classes?

A

Class I and Class II

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7
Q

Class I MHC proteins

  • Where are these present?
  • What pathway do they operate and what do they do?
  • What happens when the cell is abnormal?
  • Which cell type do these activate?
A
  • All nucleated cells
  • Endogenous pathway, pick up intracellular peptides and present them on its surface
  • Cytoplasm contains non-self peptide or viral proteins, these are presented by the MHC I proteins
  • activate CD8 cells
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8
Q

Class II MHC proteins

  • Where are these types present?
  • What pathway do they operate and what do they do?
  • What is the name of the 2 processes that they undertake?
  • What cell type do they activate and how?
A
  • Present: macrophage membrane and dendritic cells (antigen presenting cells)
  • Exogenous pathway i.e. engulf extracellular protein and present on cell surface
  • Antigen processing and antigen presentation
  • APC travels to lymph nodes and activates CD4 cells
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9
Q

What are the 5 main functions of the liver?

A
  1. Metabolism
  2. Filtration
  3. Formation
  4. Synthesis
  5. Storage
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10
Q

Liver: Metabolism

- What 6 things does the liver metabolise?

A
  1. Carbohydrates
  2. Proteins
  3. Fats
  4. Hormones
  5. Foreign chemicals (xenobiotics)
  6. Drugs
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11
Q

Liver: Filtration

- What cell types filter the blood as it passes through the liver?

A

Kupffer Cells

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12
Q

Liver: Formation

- What 2 things does the liver form?

A

Bile

Coagulation factors

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13
Q

Liver: Synthesis

- What 6 things does the liver synthesise?

A
  1. Plasma proteins
  2. Glucose
  3. Ketone bodies
  4. Cholesterol
  5. Fatty acids
  6. Amino acids
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14
Q

Liver: Storage

- What 4 things does the liver store?

A
  1. Vitamins
  2. Iron
  3. Glycogen
  4. Blood
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15
Q

Anatomy of the Liver

  • What is the basic functional unit of the liver called?
  • What shape is this structure?
  • What is this structure constructed around?
A

Liver lobule
Cylindrical structure several millimeters in length
Central vein, which empties into the hepatic vein and the vena cava

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16
Q

Anatomy of the Liver

  • What is the liver lobule composed principally of?
  • What does its arrangement resemble?
A
  1. Cellular plates

2. Radiate from the central vein like spokes in a wheel

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17
Q

Anatomy of the Liver

  • How many cells thick is the hepatic plate?
  • What structure lies between each hepatic cell?
  • Where do these structures drain?
A
  1. Two cells thick
  2. Small bile canaliculi
  3. Into bile ducts in the fibrous septa which separates adjacent liver lobules
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18
Q

Anatomy of the Liver

  • What structure is located within the fibrous septa?
  • How are these structures supplied?
  • What structures allow passage of venous blood through the liver?
A
  1. Small portal venules
  2. Mainly from the venous blood of the GI tract via the hepatic portal vein
  3. Hepatic sinusoids
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19
Q

Anatomy of the Liver

  • Where are the hepatic arterioles located?
  • What is the role of these vessels?
  • Where do these commonly drain?
A
  1. Interlobular septa
  2. Supply arterial blood to the septal tissue between adjacent lobules
  3. Drain into the hepatic sinusoids
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20
Q

Anatomy of the Liver

  • What 2 cells line the sinusoids?
  • What are “Kupffer” cells?
A
  1. Endothelial cell and Kupffer cell

2. Resident macrophages, line sinusoids and engulf bacteria and cellular debris

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21
Q

Anatomy of the Liver

  • What word is used to describe the endothelial cells of the sinusoid?
  • What name is given to the area between the endothelial cells and the hepatocytes?
A
  1. Fenestrated

2. spaces of Disse (perisinusoidal spaces)

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22
Q

Anatomy of the Liver

  • Where do the spaces of Disse connect?
  • Excess fluid in these spaces is drained by what?
  • What feature of these pores means that substances in the plasma move freely into these spaces?
A
  1. Lymphatic Vessels in the interlobular septa
  2. The lymphatic system
  3. Large pores
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23
Q

Anatomy of the Liver

  • What is Zone 1 known as?
  • What do the cells in Zone 1 do?
A
  1. Periportal

2. Amino acid catabolism, gluconeogenesis, cholesterol synthesis

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24
Q

Anatomy of the Liver

  • What is Zone 3 known as?
  • What do the cells in Zone 3 do?
  • What is the main function of Zone 3?
A
  1. Pericentral
  2. Lipid synthesis, ketogenesis, glutamine synthesis, drug metabolism
  3. Drug detoxification
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25
Q

Anatomy of the Liver

- Where does bile production occur within the liver?

A

Within all zones

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26
Q

Anatomy of the Liver

  • What 2 features regarding the liver vascular are present?
  • What is the total average blood flow rate through the sinusoid per minute?
A
  1. High blood flow and low vascular resistance

2. 1350 ml/min

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27
Q

Anatomy of the Liver

  • What is the normal pressure in the portal vein?
  • What is the normal pressure in the hepatic vein?
A
  1. 9mmHg

2. 0 mmHg

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28
Q

Cirrhosis

  • What does this cause to the resistance to blood flow?
  • What 3 changes occur with cirrhosis?
  • Name 4 causes of cirrhosis
A
  1. Increases resistance
  2. Liver parenchymal cells are destroyed, they are replaced with fibrous tissue which contracts around blood vessels and impedes flow of blood through the liver

Causes: Alcoholism, Ingestion of poisons e.g. carbon tetrachloride, viral disease e.g. hepatitis, obstruction of the bile ducts

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29
Q

Cirrhosis

- What 4 things happen when the portal system becomes blocked by a large clot?

A
  1. Blockage of the portal system by a clot
  2. Prevents return of blood from intestines and spleen, through the liver into systemic circulation
  3. Causes an increase capillary pressure in intestinal wall of 15-20 mmHg above normal
  4. Patient often dies within a few hours due to excessive loss of fluid from capillaries into the lumen and wall of intestines
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30
Q

The Liver

  • What is the normal blood volume of the liver?
  • What happens to the blood volume in the liver with increased right atrial pressures?
  • What condition is likely to cause the above events?
A

Normal Blood Volume: 450mL

Increased right atrial pressures: backflow into the liver, the liver expands causing 0.5-1 litre of extra blood in the hepatic veins and sinuses

Cardiac failure with peripheral congestion

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31
Q

In regards to blood, what can the liver act as?

A

Blood reservoir in times of excess blood volume and also supplies blood in times of diminished blood volume

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32
Q

What is the normal protein concentration of lymph draining from the liver?

What percentage of lymph produced under resting conditions does the liver contribute to?

A

6g/dl (slightly less than the protein concentration of plasma)

Half of all the lymph in the body

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33
Q

Define ascites

A

When high hepatic vascular pressures cause fluid transudation into the abdominal cavity from the liver and portal capillaries

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34
Q

Ascities

  • When the pressure in the hepatic veins rises what happens?
  • What is the composition of the ascitic fluid?
A

Happens: Xs fluid transudes into the lymphatics and leaks through the liver capsule into the abdominal cavity

Composition: pure plasma, lacking plasma protein and so encourages most fluid to enter the abdominal cavity down a concentration gradient

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35
Q

Ascities

What does blockage of the portal flow through the liver result in?

A

Result: High capillary pressures in the entire portal vascular system of the GI tract, resulting in oedema of the gut wall and transudation of fluid through the serosa of the gut into the abdominal cavity –> ascities

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36
Q

Which 2 factors promote liver regeneration?

A
  1. Hepatocyte Growth Factor (HGF)

2. Epidermal Growth Factor (EGF) and cytokines

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37
Q

How does HGF promote liver regeneration?

Which cell type produces HGF?

A

HGF

  1. Promotes differentiation of hepatic progenitor cells into hepatocytes
  2. Mesenchymal cells NOT hepatocytes
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38
Q

Give 2 examples of cytokines which promote liver regeneration

A

TNF and IL-6

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39
Q

Which cytokine terminates hepatic cell division?

Which cells secrete this cytokine?

A

Transforming Growth Factor Beta (TGF-Beta)

Hepatic cells

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40
Q

Metabolic Function: Carbohydrate Metabolism

Name the process which allows the liver to remove excess glucose from the blood, store it and then return it to the blood when blood glucose concentration falls too low

A

Glucose buffer function

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41
Q

What is the purpose of gluconeogenesis?

What two components are used in this process?

A

Utilised to restore blood glucose concentrations to normal when they fall

Amino acids and glycerol from triglycerides are converted into glucose

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42
Q

Liver: oxidation of fatty acids to derive energy

  • What is fat split into?
  • How is acetly coenzyme A formed?
  • Which biological process does acetyl co-A enter to liberate huge amounts of energy?
A
  1. Glycerol and fatty acids
  2. Fatty acids are split via “beta-oxidation” into two-carbon acetyl radicals which form acetyl-coA
  3. Citric acid cycle, where it is oxidised to liberate many amounts of acetyl-coA
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43
Q

Liver: oxidation of fatty acids to derive energy

The liver can’t utilise all acetyl-coA formed so by what type of reaction and which molecule is produced to allow other tissues to utilise this energy?

How do these tissues derive the energy from this new molecule?

A

Condensation of two molecules of acetyl-coA into acetoacetic acid

Derive the energy by reconverting acetoacetic acid into acetyl-coA and oxidising these to liberate the energy stored within this molecule

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44
Q

Liver: Synthesis of Cholesterol and Phospholipids

What percentage of total cholesterol synthesised in the liver is converted to bile salts?

The remainder is transported in what protein in the blood to other body tissues?

What are phospholipids transported by?

A

Bile salts: 80% of cholesterol

Lipoproteins

Principally lipoproteins

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45
Q

Name 3 things that both cholesterol and phospholipids are used for

A

Uses:

  1. Plasma membrane formation
  2. Intracellular structures
  3. Multiple chemical substances used in cellular function
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46
Q

Liver: Fat Synthesis

What 2 substances are used to produce fat?

How is fat transported within the body to adipose tissue?

A

Produce fat:

  1. Carbohydrates
  2. Proteins

Fat transportation: Lipoproteins

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47
Q

Liver: Protein Metabolism

Name 4 important functions of the liver in regards to protein metabolism

A

Protein Metabolism:

  1. Deamination of amino acids
  2. Formation of urea for removal of ammonia from the body fluids
  3. Formation of plasma proteins
  4. Transamination to form non-essential amino acids
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48
Q

Liver: Deamination of amino acids

Why is this required?

Which other tissue is capable of this process but in small amounts?

A

Required: before they can be used for energy or converted into carbohydrates or fats

The kidneys

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49
Q

Liver: Formation of Urea

  • What is the outcome of this process?
  • What can result if the liver does not undertake this process?
A

Outcome: Removes ammonia from bodily fluids

Can result: Hepatic coma and death (due to high plasma ammonia concentration)

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50
Q

Liver: Formation of plasma proteins

  • All except which protein is formed by hepatic cells?
  • What does depletion of plasma proteins cause?
A

All except: gamma globulins i.e. antibodies (formed by plasma cells)

Depletion causes rapid mitosis of the hepatic cells and growth of the liver to a larger size, coupled with rapid output of plasma proteins until normal concentrations are produced

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51
Q

Liver: Formation of plasma proteins

In chronic liver disease e.g. cirrhosis, plasma proteins may fall to a very low level resulting in which 2 symptoms?

A

Symptoms: Oedema and ascites

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52
Q

Liver: Transamination to form non-essential amino acids

What are the two steps of this process?

A

First Step: Synthesis of a keto-acid with the same chemical composition (except at the keto-oxygen) as the amino acid to be formed

Second step: Transfer of the amino radical through several transamination stages from an available amino acid to the keto-acid to take the place of the keto oxygen

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53
Q

Liver: Vitamin Storage

Name 3 vitamins which are stored within the liver

A

Three vitamins:

  1. Vit A
  2. Vit D
  3. Vit B12
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54
Q

Liver: Vitamin Storage

The storage of the following vitamins can prevent deficiency for how long within the body:

  1. Vit A
  2. Vit D
  3. Vit B12
A

Vit A: up to 10 months
Vit D: up to 3-4 months
Vit B12: at least 1 year (maybe several)

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55
Q

Liver: Ferritin Store

What protein do the hepatic cells contain that binds reversibly with iron?

What happens when there is excess iron within the body?

What happens when there is low iron within the body?

A

Contains apoferritin

Excess iron within the body:

  • Iron combines with apoferritin to form ferritin
  • Stored in the hepatocytes until needed elsewhere

Low iron within the body:
- Ferritin releases the iron

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56
Q

Liver: Ferritin Store

What name is given to the process through which blood iron concentration is regulated?

A

The apoferritin-ferritin system of the liver

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57
Q

Name 4 coagulation factors produced by the liver

A
  1. Fibrinogen
  2. Prothrombin
  3. Accelerator globulin
  4. Factor VII
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58
Q

Which vitamin is required by the liver for the formation of prothrombin and Factors VII, IX and X?

A

Vitamin K

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59
Q

Name 4 drugs which are excreted in the bile?

A
  1. Sulphonamides
  2. Penicillin
  3. Ampicillin
  4. Erythromycin
60
Q

Essentially all of which type of hormone are excreted by the liver?

A

Steroid hormones e.g. Oestrogen, cortisol and aldosterone

61
Q

What name is given to the progenitor stem cells of the liver?

A

Oval cells

62
Q

What cell type is only produced in the liver within the foetus?

A

Erythrocytes

63
Q

Which cell type in the liver is the major type involved in liver fibrosis?

A

Hepatic Stellate Cells (Ito cells)

64
Q

What is the major end product of haemoglobin degradation which is eliminated in the faeces?

A

Billirubin

65
Q

What are the 4 excretory functions of bile?

A

Excretion of:

  1. waste products which can;t be easily excreted by the kidneys
  2. Hormones
  3. Drugs
  4. Xenobiotics
66
Q

What are the 2 secretory functions of bile?

A

Secretion of:

  1. Bile acids/salts to aid intestinal lipid digestion and absorption
  2. Electrolytes and water as a vehicle
67
Q

Synthesis of bile acids/salts

  • What are bile acids derived from?
  • Where are primary bile acids produced and name two examples
A

Derived from cholesterol

Primary bile acids: in the liver
2 examples: Cholic Acid and Chenodeoxycholic acid

68
Q

Synthesis of bile acids/salts

  • Where are secondary bile acids produced?
A

Secondary bile acids are produced in the intestine via bacterial action

69
Q

What are primary and secondary bile acids conjugated with which makes them more water soluble and charged?

A
  1. Taurine
  2. Glycine
  3. Sulphate
  4. Glucuronate
70
Q

Name 2 transporters which secrete conjugated and unconjugated bile salts

What type of transporters are these?

A
  1. Bile salt export pump (BSEP)
  2. Multidrug resistance associated protein 2 (MRP2)

Type of ABC transporters
(ATP Binding Cassette Transporters)

71
Q

Reabsorption of bile acids

What is the process for unconjugated bile acids?

A

Unconjugated: passive reabsorption across the proximal intestinal wall
(lipid soluble)

72
Q

Reabsorption of bile acids

What is the process for conjugated bile acids?

A

Conjugated: active uptake in the terminal ileum via Na+ bile salt (co)transporter [ASBT] and organic solute transporter [OST]

73
Q

What name is given to the cells which line the biliary tree/duct?

A

Cholangiocytes

74
Q

What 2 properties does bile have?

A
  1. HC03- rich

2. Isosomotic fluid

75
Q

What 3 mechanisms cause bile secretion?

A
  1. Secondary active transport of Cl- and HC03-
  2. Paracellular Na+ transport
  3. Isosmotic water flow
76
Q

Name 4 things which stimulate bile secretion of bile

A
  1. CCK
  2. Secretin
  3. VIP
  4. Glucagon
77
Q

What inhibits bile secretion?

A

Somatostatin

78
Q

Name 3 major plasma proteins and their associated function

A
  1. Albumin: colloid osmotic pressure
  2. Globulin - immunity
  3. Fibrinogen - fibrin to form clots
79
Q

What 3 pathways can amino acids follow if they are present in excess?

A
  1. Degraded via the urea cycle
  2. Gluconeogenesis
  3. Ketogenesis
80
Q

What reaction takes place for amino acid catabolism?

A

Transamination reaction
i.e. an amino radical is transferred to a alpha-keto acid and the keto oxygen is transferred to the donor of the amino radical

81
Q

What is ALT?

What is it a specific indicator of if raised in the serum?

A

Alanine Transaminase

Liver damage

82
Q

What is AST?

Is it a more specific or more sensitive marker and why?

A

Aspartate Transaminase

More sensitive as the liver contains larger amounts of AST than ALT

83
Q

What is a deamination reaction?

A

Removal of amino groups from amino acids

84
Q

In the process of deamination, if NH3 is formed in the peripheral tissues what is it converted to?

A

Peripheral tissues: glutamine

85
Q

In the process of deamination, if NH3 is formed in muscle what is it converted to?

A

Muscle: alanine

86
Q

Which 2 enzymes in the liver can liberate NH3 from glutamine?

What results and feeds into the urea cycle?

A

Glutaminase

Glutamate Dehydrogenase

Aspartate feeds into the urea cycle for elimination

87
Q

What process delivers ammonia to the liver for removal as urea if muscle is the tissue of origin?

A

The alanine-glucose shuttle

Alanine delivers NH3 via ALT

Pyruvate enters glyconeogenesis and the glucose is returned to the muslce

88
Q

In the urea cycle, how many molecules of ammonia and bicarbonate are converted to urea?

A

2 molecules of ammonia

1 bicarbonate

89
Q

How is urea excreted from the body?

A

Shuttled from the liver to the kidneys –> urine

90
Q

If liver pathology causes ammonia accumulation in the blood what condition can result?

A

Hepatic Encephalopathy/Coma

91
Q

What is gluconeogenesis?

A

Conversion of amino acids to glucose or glycogen

92
Q

What is ketogenesis?

A

Conversion of amino acids to keto acids or fatty acids

93
Q

What effect on protein metabolism does growth hormone have?

A

Increases synthesis of cellular proteins

94
Q

What effect on protein metabolism does Insulin have?

A

Needed for protein synthesis and storage

95
Q

What effect on protein metabolism does glucocorticoids have?

A

Increases breakdown of tissue proteins, thus increases the amount of amino acid concentration in the plasma

96
Q

What effect on protein metabolism does testosterone have?

A

Increases protein deposition in tissues until the maximum limit is reached

97
Q

What effect on protein metabolism does oestrogen have?

A

Causes some deposition of protein

98
Q

What effect on protein metabolism does thyroxine have?

A

Increases the rate of metabolism of all cells

  • Can degrade proteins in times of insufficient fats and carbohydrates as sources of energy
  • Can increase protein synthesis if sufficient energy sources are available
99
Q

What is hepatitis?

A

Inflammation of the liver

100
Q

What are the 7 causes of Hepatitis?

A
  1. Viral Infection e.g. Hep A
  2. Immunological e.g. autoimmune
  3. Toxins e.g. alcohol
  4. Drugs e.g. paracetamol
  5. Bacterial Infection e.g. leptospirosis
  6. Parasitic Infection e.g. hydatid
  7. Vascular congestion e.g. portal vein thrombosis
101
Q

Name 3 non-specific symptoms of hepatitis

A
  1. Fatigue
  2. Lethargy
  3. Itching
102
Q

Name 2 specific symptoms of hepatitis

A
  1. Jaundice

2. Right upper quadrant pain

103
Q

Diagnostic markers of Liver:

  • What will result if hepatitis infection is present?
  • AST>ALT is indicative of?
  • ALT>AST is indicative of?
A
  1. AST and ALT both raised
  2. Alcoholic hepatitis
  3. Many causes mainly viral
104
Q

Hepatitis A

  • Transmission Route
  • Viral Family
  • Nucleic acid structure
  • Acute infection?
  • Chronic infection?
A
  1. Enteral (Faecal-Oral)
  2. Picornavirus
  3. RNA single stranded with no envelope
  4. Yes - self limiting
  5. No
105
Q

Hepatitis B

  • Transmission Route
  • Viral Family
  • Nucleic acid structure
  • Acute infection?
  • Chronic infection?
A
  1. Parenteral (IVDU, blood transfusion, sex, vertical)
  2. Hepadnavirus
  3. DNA double stranded with an envelope
  4. Yes
  5. Yes, can develop into cirrhosis and hepatocellular carcinoma
106
Q

Hepatitis C

  • Transmission Route
  • Viral Family
  • Nucleic acid structure
  • Acute infection?
  • Chronic infection?
A
  1. Parenteral (IVDU, blood transfusion, sex, vertical)
  2. Flavivirus
  3. RNA single stranded with an envelope
  4. Yes
  5. Yes, can develop into cirrhosis and hepatocellular carcinoma
107
Q

Hepatitis D

  • Transmission Route
  • Viral Family
  • Nucleic acid structure
  • Acute infection?
  • Chronic infection?
A
  1. Parenteral (IVDU, blood transfusion, sex, vertical transmission)
  2. Deltavirus (isn’t a true virus)
  3. RNA single stranded with an envelope
  4. Yes, but requires coinfection with Hep B
  5. Yes, can develop into cirrhosis and hepatocellular carcinoma
108
Q

Hepatitis E

  • Transmission Route
  • Viral Family
  • Nucleic acid structure
  • Acute infection?
  • Chronic infection?
A
  1. Enteral (Faeco-oral)
  2. Hepevirus
  3. RNA single stranded with no envelope
  4. Yes, “self-limited” fulminant in pregnancy
  5. No
109
Q

Hepatitis: Antigens

What does surface antigen (sAg) indicate?

A

Presence of the virus in the body

110
Q

Hepatitis: Antigens

What do core antigens (cAg) indicate?

A

The body is producing antibodies against the virus (infection present)

111
Q

Hepatitis: Antigens

What do modified core antigens (eAg) indicate?

A

Virus is actively replicating and that the person has increased infective status.

112
Q

Using Hepatitis B as an example:

What does anti-HBc antibody mean?
What does Anti-HBc antibody mean?
What does Anti-HBe antibody mean?

A
  1. Immunity against HBV
  2. IgM = acute infection, IgG = chronic infection
  3. Presence reduces infectability
113
Q

What receptor does the HBV bind to gain access to the hepatocyte?

A

NTCP bile receptor

114
Q

What is HBsAg?

A

Surface antigen found on the envelope of HBV

115
Q

What is HBcAg?

A

Core antigen found around the nucleus of HBV

116
Q

What is HBeAg?

A

Modified C antigen that appears when the viral cell is actively replicating (infectious)

117
Q

What does anti-HBs antibody indicate?

A

Indicative of immunity against HBV

118
Q

What does anti-HBc antibody indicate?

A

Antibody to the core HBV antigen
If IgM then is acute infection
If IgG then is a chronic infection

119
Q

What does anti-HBe antibody indicate?

A

Antibody to the actively replicating c antigen, would reduce the infectious status of the individual

120
Q

Combination of which 2 things would indicate a chronic HBV infection?

A

Anti-HBc IgG

HBsAg

121
Q

Combination of which 2 things would indicate complete immunity against infection?

A

Anti-HBc IgG

Anti-HBsAg

122
Q

What are the four phases of the HBV life cycle?

A
  1. Immune tolerance
  2. Immune clearance
  3. Low replication inactive carrier
  4. Reactivation
123
Q

Name a drug which stimulates clearance of infected cells in HBV infection

A

Pegylated Interferon

124
Q

Name 2 drugs which are nucleoside/nucleotide analogues in the treatment of HBV infecton

A

Tenofovir

Entecavir

125
Q

What is Jaundice?

A

Yelllowish tint to the body tissues e.g. skin and deep tissues

126
Q

What causes jaundice?

A

large quantities of free or conjugated bilirubin in the extracellular fluids

127
Q

What is the normal plasma concentration of bilirubin in mg/dl?

A

0.5mg/dl of plasma

128
Q

At what plasma concentration of bilirubin in mg/dl does the skin usually appear jaundice?

A

> 1.5mg/dl

129
Q

Worldwide, what are the most common causes of cirrhosis?

A
  1. Chronic viral hepatitis (B or C)

2. Prolonged excessive alcohol consumption (causes a rise in the MCV and enzyme GGT)

130
Q

What is the most common cause of portal hypertension and its associated complications?

A

Hepatic Cirrhosis

131
Q

What are the 3 cardinal features of cirrhosis?

A
  1. Increase in fibrous tissue
  2. Progressive and widespread death of liver cells
  3. Inflammation leading to loss of normal liver architecture
132
Q

Define Cirrhosis

A

Histological diagnosis characteristic of diffuse hepatic fibrosis and nodule formation
Typically affecting the whole liver

133
Q

Liver function tests (LFTs) are markers of what?

A

Biochemical markers of liver cell damage

134
Q

What does a raised bilirubin indicate?

In which type of disease does this increase earlier in the disease progression?

A

Degree of elevation reflects degree of severity of liver damage

Primary biliary cirrhosis, rather than cirrhosis

135
Q

What happens to serum albumin in liver disease?

Why does this occur?

A

Levels are reduced

Change in the volume of distribution of albumin and a reduction in the synthesis of

136
Q

What might happen to albumin concentration in acute liver failure vs chronic liver failure?

A

Plasma half-life is ~2 weeks

  • In acute liver failure: may be normal
  • In chronic liver failure: almost always reduced
137
Q

LFTs: Alanine Aminotransferase and Asparate Aminotransferase

What is the normal function?

A

Normal:

  • ALT transfers amino group to a ketoacid to form pyruvate
  • AST transfers amino group to a ketoacid to form oxaloacetate
138
Q

Where are ALT and AST located?

A

Both within the hepatocyte cytoplasm

AST located in the mitochondrial cytoplasm

139
Q

LFTs: ALT and AST

Which enzyme is more specific for hepatocellular damage?

A

ALT

  • Expression outside the liver is relatively low
  • Considered more specific for hepatocellular damage
140
Q

What type of damage is indicative of large increases (>300 U/L) of aminotransferase activity?

A

Hepatitic

- Favours hepatocellular damage

141
Q

LFTs: ALP

What does ALP stand for?

A

Alkaline phosphatase

- Several enzymes that are capable of hydrolysing phosphate esters at alkaline pH

142
Q

LFTs: ALP

Where are ALPs located?

A

Cell membranes in hepatic sinusoids and biliary canaliculi/ducts

143
Q

LFTs: ALP

What is a rise in plasma ALP indicative of?

A

Intrahepatic and extrahepatic biliary obstruction and with sinusoidal obstruction (infiltrative liver disease)

144
Q

LFTs: GGT

What does GGT stand for?

A

GGT: Gamma Glutamyl Transferase

145
Q

LFTs: GGT

What is GGT?

A

Microsomal enzyme produced in high concentrations within hepatocytes and by the epithelium lining small bile ducts

146
Q

LFTs: GGT

What is the function of GGT?

A

Function: Transfer glutamyl groups from gamma-glutamyl peptides to other peptides and amino acids

147
Q

What LFT pattern indicates obstructive/cholestatic liver disease?

A

Modest increase in aminotransferase and large increases in ALP and GGT activity

Case 5 (1 decks)

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