1
Q
What are the causes of metabolic acidosis?
A
- Renal disease
- Diabetic ketoacidosis
- Lactic acidosis caused by tissue anoxia (deprivation of oxygen) or liver disease
- Certain cases of over dosage or poisoning
- Chronic diarrhoea or intestinal fistula
- Renal tubular acidosis
2
Q
What are the clinical effects of acidosis?
A
- Hyperventilation
- Neuromuscular irritability
- Hazard of arrythmias progressing to cardiac arrest (more likely in presence of hyperkalaemia)
- Depression of consciousness which can progress to coma and death
3
Q
What are the causes of metabolic alkalosis?
A
- Loss of hydrogen ions in gastric fluid during vomiting
- Potassium deficiency (often a consequence of diuretic therapy)
- Ingestion of an absorbable alkali such as sodium bicarbonate (very large dosage required)
4
Q
What are the clinical effects of metabolic alkalosis?
A
- Hypoventilation
- Confusion
- Coma
- Muscle cramps
- Paraesthesia
- Tetany
5
Q
What are some examples of acute respiratory acidosis?
A
- Choking
- Bronchopneumonia
- Acute exacerbation of asthma/chronic obstructive pulmonary disorder (COPD)
6
Q
What are some examples of acute respiratory alkalosis?
A
- Hysterical over-breathing
- Mechanical over-ventilation in an intensive care patient
- Raised intracranial pressure, or hypoxia, both of which stimulate the respiratory centre
7
Q
What are some examples of mixed acid-base disorders commonly encountered?
A
- Hyperventilation causes respiratory alkalosis, with prolonged nasogastric suction that causes metabolic alkalosis
- A patient with respiratory acidosis due to COPD and diuretic-induced potassium depletion causing metabolic alkalosis
- Salicylate poisoning in which respiratory alkalosis occurs due to stimulation of respiratory centre, together with metabolic acidosis due to the effects of the drug on metabolism
8
Q
What is alanine aminotransferase (ALT) used to indicate?
A
Liver damage more specifically hepatocellular damage
9
Q
What is amylase and lipase used to indicate?
A
Cell damage in acute pancreatitis
10
Q
What is creatine kinase used to indicate?
A
Skeletal muscle damage
11
Q
What is alkaline phosphatase (ALK) used to indicate?
A
- Increases in cholestatic liver disease
* Marker of osteoblast activity in bone disease
12
Q
What is gamma-glutamyl transpeptidase (GGT) used to indicate?
A
A sensitive but non-specific liver disease marker
13
Q
What is aspartate aminotransferase (AST) used to indicate?
A
- Hepatocellular damage
- Muscle damage
- Haemolysis
14
Q
What is required to diagnose a patient with myeloma?
A
At least two of the following
• A paraprotein in serum or urine
• Plasma cell infiltration in bone marrow
• Myeloma-related end-organ damage including skeletal lesions
15
Q
What are some cardiac specific biomarkers for a myocardial infarction?
A
- Troponin I
* Troponin T
16
Q
How long after the symptoms of a myocardial infarction do the troponin molecules arise?
A
Within a few hours
17
Q
How long do troponin molecules stay elevated after symptoms of a myocardial infarction?
A
1-2 weeks
18
Q
What can be the cause of elevated troponin molecules?
A
- Myocardial infarction
- Myocarditis
- Pulmonary embolism and stroke
- Non-cardiac conditions (severe sepsis)
19
Q
What conditions do the liver function tests assist in differentiating?
A
- Acute hepatocellular damage
- Obstruction to the biliary tract
- Chronic liver disease
20
Q
What does a liver function test include?
A
- Alanine aminotransferase (ALT)
- Bilirubin
- Alkaline phosphatase (ALK)
- Albumin
- Aspartate aminotransferase (AST)
- Gamma-glutamyl transpeptidase (GGT)
- Prothrombin time
21
Q
Why might the levels of bilirubin in the blood rise?
A
- Haemolysis
- Failure of the conjugating mechanism within the hepatocyte
- Obstruction in the biliary system
22
Q
What are some examples of things that can block the bile duct (extrahepatic biliary obstruction)?
A
- Gallstones
- Pancreatic cancer
- Lymph nodes
23
Q
What are the most common reasons for acute liver damage?
A
- Poisoning
- Infection
- Inadequate perfusion
24
Q
What ways can acute liver damage progress?
A
- It may resolve, as it does in most cases
- It may progress to acute hepatic failure
- It may lead to chronic hepatic damage
25
What are some examples of chronic liver damage?
* Alcoholic liver disease
* Chronic active hepatitis
* Primary biliary cirrhosis
* Non-alcoholic fatty liver disease
26
What are the most common causes of cirrhosis?
* Chronic excess alcohol ingestion
* Viral hepatitis
* Autoimmune diseases
27
What is an unusual cause of cirrhosis?
* Can develop as a child due to α1-antitrypsin deficiency
* Can develop as a child due to Wilson’s disease
* Can develop in adults due to haemochromatosis
* Can follow chronic ingestion of pyrrolizidine alkaloids (found in some herbal teas)
28
What conditions can result in secondary diabetes mellitus?
* Pancreatic disease
* Endocrine disease (Cushing’s syndrome)
* Drug therapy
* Insulin receptor abnormalities (rarely)
29
What are micronutrients?
* Minerals
* Trace elements
* Required in small amounts but not of limited importance
30
What biochemical tests would be requested for suspected poisoning and why?
• Serum urea, electrolytes, and liver function tests to assess kidney and liver function
• Blood glucose to exclude hypoglycaemia
• Blood gases to assess acid-base status
Additional tests may be required
31
How is a diagnosis of metal poisoning done?
* Plasma or blood levels of the metal
* Urinary excretion of metals
* An associated biochemical abnormality related to the toxicity
32
Why do some patients with malignancies have renal failure?
* Obstruction of the urinary tract
* Hypercalcaemia
* Bence-Jones proteinuria
* Hyperuricaemia
* Nephrotoxicity of cytotoxic drugs
33
What does a higher than normal concentration of alpha-fetoportein (AFP) mean in foetal monitoring?
```
• Central nervous defects
o Anencephaly
o Spina bifida
• Neural tube defect
• Placental disruption
• Liver disease
• Foetal or maternal tumours
• Wrong dates (usually does not increase after 32 weeks)
• Multiple pregnancies
```
34
What is screened for in antenatal screening?
* Foetal screening for Down syndrome and spina bifida
* Foetal anomaly screening by ultrasonography to identify congenital heart defects, cleft lip and confirm spina bifida
* Sickle-cell and thalassaemia
* HIV
* Hepatitis B
* Syphilis
* Rubella
35
What is some common Point of care testing (POCT) in blood?
* Blood gases
* Glucose
* Urea and creatinine
* Na, K and Ca
* Bilirubin
* Salicylate
* Paracetamol
* Alcohol
* Troponin
36
What is some common Point of care testing (POCT) in urine?
* Glucose
* Ketones
* Red cell/haemoglobin
* Bilirubin
* Urobilinogen
* pH
* Protein
* hCG
* Drugs of abuse
37
What does high doses of mineralocoticoids initially lead to?
* Sodium retention
* Modest expansion of the extracellular fluid (ECF) volume (not to the extent of oedema)
* Sodium balance is then restored
38
When measuring urine osmolality and sodium, how can the results be misleading?
If the patient is on steroids or diuretics
39
Why would plasma appear turbid to the naked eye?
The patient has severe hyperlipidaemia
40
What is chronic mild hyperkalaemia (5-6 mmol/L) a relatively common finding in?
* Elderly patients
| * Acute or chronic kidney disease
41
What is hydrogen ion concentration usually measured in?
Arterial blood anticoagulated with heparin
42
What are the components that can be identified in the pathophysiology of hydrogen ion disorders (acid-base disorders)?
* Generation
* Buffering
* Compensation
* Correction
43
What does acidosis signify?
A tendency for the hydrogen ion concentration to be above the reference range
44
What does alkalosis signify?
A tendency for the hydrogen ion concentration to be below the refernece range
45
What is the primary abnormality in non-respiratory (metabolic) acidosis?
* Either increased production or decreased excretion of hydrogen ions other than from carbon dioxide
* Loss of bicarbonate from the body can indirectly cause acidosis
46
What is a flial segment?
* When ribs are broken in two places, the chest wall that they support cannot expand during inspiration.
* The negative intrathoracic pressure causes it to move inwards compromising ventilatory function
47
What can cause acidosis?
* Retention of carbon dioxide
| * Ingestion/increased production/decreased excretion of acid or loss of bicarbonate
48
What can cause alkalosis?
* Hyperventilation leading to a fall in PCO2
| * Increased loss of acid
49
What is Rituximab?
A monoclonal antibody used to treat cancer
50
How does Rituximab work?
* Binds to protein CD20 on the surface of immature B cells, and marks these cells for destruction by antibody-dependent cellular cytotoxicity
* This slows the growth of metastases
51
What are the major functions of the kidneys?
* Excretion of waste
* Maintenance of extracellular fluid (ECF) volume and composition, including acid-base balance
* Hormone synthesis
* Contribute to glucose supply in the fasting state through gluconeogenesis
52
What are some measurements of glomerular filtration rate?
* Clearance
* Plasma creatinine
* Plasma urea
* Cystatin C
* Estimated glomerular filtration rate
53
When is estimated glomerular filtration rate not applicable?
* Acute kidney disorders
* Pregnancy
* In condition in which there is severe muscle wasting or oedmatous states (increased creatinine levels)
* In children
* Increased muscle mass in athletes and body builders
* Malnutrition and obesity
* After a meat-rich meal
54
What is acute kidney injury (AKI) characterized by?
* Rapid loss of renal function
* Retention of urea, creatinine, hydrogen ions and other metabolic products
* Usually but not always oliguria
55
What is teh renal functional impairment in pre-renal acute kidney injury related to?
A decrease in renal blood flow
56
What is the renal functional impairment in intrinsic acute kidney injury related to?
Intrinsic damage to the kidenys
57
What is the renal functional impairment in post-renal acute kidney injury related to?
Urinary tract obstruction
58
What is uraemia?
Urine in the blood
59
What is azotaemia?
Refers to an increase in the blood concentration of nitrogenous compounds
60
What are some conditions that lead to a decrease in the number of functioning nephrons?
* Glomerulonephritis
* Diabetes mellitus
* Hypertension
* Pyelonephritis
* Renovascular disease
* Polycystic kidneys
61
What are some examples of renal diseases that affect the tubules and has "salt-losing nephritis" syndrome?
* Analgesic nephropathy
* Polycystic disease
* Chronic pyelonephritis
62
What conditions is impairment of urinary concentration a feature?
* Nephrogenic diabetes insipidus
* Group of primary tubular disorders
* Cranial diabetes insipidus
* Chronic kidney disease
63
What conditions can impairment of urinary concentration occur with?
* Hypercalcaemia
* Hypokalaemia
* Certain drugs (notably lithium)
64
What are the most common disease processes that affect the liver?
* Hepatitis (acute or chronic or both)
* Cirrhosis
* Tumours (primary and secondary - more frequently secondary)
65
What is bilirubinuria?
An increase in the plasma concentration of conjugated bilirubin and is always pathological (caused by disease)
66
What does prothrombin time test?
* Plasma clotting activity
| * Reflects the activity of vitamin K-dependent clotting factors synthesized by the liver
67
What does prothrombin time indicate?
* Early feature of acute liver disease
| * Prolonged prothrombin time can be an indicator of vitamin K deficiency
68
What can transcutaneous ultrasound examination reveal?
* Gallstones
* Dilation of the biliary system
* Tumours
* Characteristic hyperechoic nature of hepatic fatty infiltration
69
What is an endoscopic ultrasound good for looking at?
* Visualizing pancreas
| * Portal vein
70
What is the doppler ultrasonography used for?
* Assess blood flow
| * Patency of blood vessels supplying the liver
71
What is elastography used to determine?
The degree of liver fibrosis
72
In adults, what is almost always the cause of severe jaundice?
Conjugated hyperbilirubinaemia
73
What is the colour of urine containing water-soluble conjugated bilirubin?
Deep orange-brown colour
74
What colour is the stool of a patient with complete biliary obstruction and why?
Pale in colour as no bilirubin reaches the gut therefore no stercobiln is formed to make the stool a darker colour
75
What is cholangography used to examine?
The biliary system
76
What does arteriography examine?
The pathological circulation in hepatic tumours
77
What does computed tomography (CT) and magnetic resonance imaging examine?
Structural abnormalities and space-occupying lesions in the hepatobiliary system
78
In diagnosing chronic liver disease, histology is the gold standard, how is the tissue obtained?
By percutaneous biopsy
79
What is chronic hepatitis defined as?
Hepatic inflammation persisting for more than 6 months
80
What are some causes of chronic hepatitis?
* Autoimmune hepatitis
* Chronic infection with hepatitis B or C
* Alcohol consumption
81
What are the metabolic features of acute liver failure?
* Severe hyponatraemia
* Hypocalcaemia
* Hypoglycaemia
* Lactic acidosis often masked by respiratory alkalosis
* Depression of brain stem which can lead to respiratory arrest
* Metabolic alkalosis due to potassium depletion
* Prolonged prothrombin time
* Low plasma urea concentration
82
What is cirrhosis?
A process in which death of liver cells with regeneration leads to fibrosis, scarring and destruction of the normal liver architecture
83
What is primary biliary cirrhosis?
Progressive autoimmune disease characterized by destruction of intrahepatic bile ducts, typically affecting middle-aged women
84
What complications can be made from decreased hepatic function and disturbances of liver architecture?
* Hepatic encephalopathy
* Bleeding from oesophageal varices
* Ascites
* Acute kidney injury
* Disturbances of endocrine function
85
What are the causes of death in a patient with hepatic cirrhosis?
* Hepatic encephalopathy
* Uncontrollable bleeding
* Septicaemia
86
Plasma IgA is often increased in what liver disease?
Alcoholic liver disease (non-specific marker)
87
Plasma IgM is often increased in what liver disease?
Primary biliary cirrhosis (non-specific marker)
88
What is ethanol a common cause of?
* Hepatic steatosis (fat accumulation in the liver) due to ethanol abuse
* Alcoholic hepatitis (life threatening condition) develops after a bout of heavy drinking in patients with a history of excessive alcohol ingestion
* Cirrhosis (not inevitable in heavy drinkers – only 10% of heavy drinkers develop it)
89
Is hepatic steatosis reversible?
Yes
90
Non-alcoholic fatty liver disease (NAFLD) is an umbrella term for which conditions?
• Wide range of conditions from simple hepatic steatosis (fat deposition alone) to non-alcoholic steatohepatitis (in which inflammation is present) which can lead to cirrhosis
91
What are primary tumours associated with?
* Cirrhosis
* Persistence of hepatitis B and C
* Various carcinogens (including aflatoxins)
92
What is a valuable marker for primary hepatocellular carinomas?
* Plasma α-fetoprotein
| * Elevated in approximately 70% of patients with primary hepatocellular carcinomas
93
In what conditions is plasma α-fetoprotein elevated in?
* Primary hepatocellular carcinoma
* Acute and chronic hepatitis (elevated to a lesser extent than primary hepatocellular carcinoma)
* Cirrhosis (elevated to a lesser extent than primary hepatocellular carcinoma)
94
What are some examples of infiltrative conditions affecting the liver?
* Lymphomas
| * Amyloidosis
95
In what liver conditions are the patients not jaundiced?
* Lymphomas
* Amyloidosis
* Intrahepatic tumours
96
What is cholestasis?
Obstruction to the normal flow of bile
97
What can cholestasis be a feature of?
* Hepatic disease (particularly cirrhosis)
| * Extrahepatic disease (carcinoma of the head of the pancreas, causing obstruction of the common bile duct)
98
What are the consequences of cholestasis?
* Fatigue
* Malabsorption (particularly of fat-soluble vitamins)
* Osteoporosis (mainly in males)
99
How does jaundice present in cholestasis?
* May not present in the early stages
| * In cholestatic jaundice the majority of the excess bilirubin is conjugated
100
What conditions are there in which jaundice is caused by an inherited abnormality?
* Gilbert syndrome
* Crigler-Najjar syndrome
* Dubin-Johnson syndrome
* Rotor syndrome
101
What is Wilson disease?
* An uncommon liver disease
* It is an inherited abnormality (autosomal recessive) of copper metabolism characterized by decreased biliary excretion of copper and decreased incorporation of copper into caeruloplasmin (a plasma protein)
102
In what conditions is a decrease in caeruloplasmin seen?
* Wilson disease
* Chronic hepatitis
* Malnutrition
103
What is haemochomatosis?
* An uncommon liver disease
* It is an inherited disorder characterized by excessive iron uptake from the gut and iron deposition in the tissues, can affect many organs including the liver
104
What is α1-Antitrypsin deficiency?
* An uncommon liver disease
* An inherited condition characterized either by the absence of this protein from the plasma or by the presence of an abnormal form of the protein
* A rare cause of cirrhosis
105
What is liver transplantation used to treat?
* Severe liver disease
| * Both acute and chronic
106
After surgery of a liver transplant, what are the major complications?
* Bleeding
* Acute kidney injury (AKI)
* Immediate non-function of the graft
* Infection
* Rejection
* (Long term) The liver disease may recur in the transplanted liver
107
What are gallstones composed of?
* Primarily of cholesterol
* Bilirubin
* Calcium salts
108
What can gallstones cause?
* May be clinically silent
* Biliary colic and obstruction
* Predispose to cholecystitis
* Predispose to pancreatitis
109
What is primary sclerosing cholangiitis (PSC)?
It is a cholestatic liver disease characterized by inflammation and progressive fibrosis of the biliary system, leading to cirrhosis and liver failure
110
What bilirubin is the cause of neonatal jaundice?
Unconjugated bilirubin
111
What does the acidic gastric juice of the stomach contain?
* Proenzyme of pepsin (pepsinogen)
| * Intrinsic factor (essential for the absorption of vitamin B12
112
What controls the secretion of the acidic gastric juices?
* The vagus nerve
| * The hormone gastrin
113
What are some examples of hypersensitivity?
* Allergy to grass pollens
* Immune complex glomerulonephritis occurring after streptococcal infection
* Chronic granulomas produced during tuberculosis or schistosomiasis
114
Which IgG subclasses are generally superior at mediating effector functions such as complement activation and ADCC?
IgG1 and IgG3 superior to IgG2 and IgG4
115
Where is monomeric IgG a major antibody found?
* Serum
| * Non-mucosal tissues
116
What does IgG do?
* Inactivates pathogens directly
| * Interacts with effectors, triggering molecules such as complement (classical pathway) and Fc receptors
117
Where is pentameric IgM found?
Serum
118
What is IgM highly efficient at triggering?
Complement (classical pathway)
119
Where are monomer and small amounts of dimeric IgA found?
Serum
120
What pathway of the complement system does IgA trigger?
Lectin pathway (mannose-binding lectin)
121
Where is monomeric IgE found?
* Serum (very low concentrations)
| * Most are bound to IgE Fc receptors on mast cells
122
Where is monomeric IgD found
On the surface of B cells as an antigen receptor
123
Where does IgA appear selectively to defend exposed external surfaces against microorganisms?
* Saliva
* Tears
* Nasal fluids
* Sweat
* Colostrum
* Milk
* Secretions of the lung
* Genitourinary
* Gastrointestinal tracts
124
What secretes gastrin?
G cells in the antrum of the stomach
125
What is most peptic ulceration associated with?
* Non-steroidal inflammatory drug use
| * Colonization of the stomach with Helicobacter pylori
126
How is H. pylori diagnosed?
* Serology
| * Stool antigen test
127
What are the endocrine productions of the pancreas?
* Insulin
* Glucagon
* Pancreatic polypeptides
* Other hormones
128
What is the exocrine excretion of the pancreas?
* An alkaline, bicarbonate-rich fluid containing various enzymes essential for normal digestion
* Proenzyme forms of proteases
* Trypsin
* Chymotrypsin
* Carboxypeptidase
* The lipolytic enzyme lipase
* Colipase
* The starch hydrolase amylase
129
The secretion of pancreatic fluid is under control of which two hormones secreted by the small intestine?
* Secretin
| * Cholecystokinin (CCK)
130
What does the secretin stimulate in the pancreas?
The secretion of alkaline fluid
131
What does cholecystokinin (CCK) stimulate in the pancreas?
* Pancreatic enzymes
* Contraction of the gallbladder
* Induces satiety
132
What are secretin and cholecystokinin (CCK) secreted in the presence of?
* Acid
* Amino acids
* Partly digested proteins in the duodenum
133
What are the major disorders of exocrine pancreas?
* Acute pancreatitis
* Chronic pancreatitis
* Pancreatic cancer
* Cystic fibrosis
134
What does acute pancreatitis present with?
* Acute abdomen
* Severe pain
* Variable degrees of shock
135
What are the most known causes of acute pancreatitis?
* Ethanol ingestion
* Gallstones
* Complication of endoscopic retrograde pancreatography (ERCP)
136
What are some less-common causes of acute pancreatitis?
* Infection (usually viral)
* Hypertriglyceridaemia
* Hypercalcaemia
137
What is the clinical diagnosis of acute pancreatitis?
* High serum amylase or lipase activity
| * Typical appearance on computed tomography (CT) scanning
138
What does chronic pancreatitis present with?
* Abdominal pain
* Malabsorption
* Impaired glucose tolerance (occasionally)
139
What enzymes are used in tests of pancreatic function?
Pancreatic elastase and chymotrypsin activities in faeces
140
Why are pancreatic elastase and chymotrypsin used in pancreatic function tests?
* These are reduced in chronic pancreatitis
| * Faecal elastase is widely used to distinguish between diarrhoea of pancreatic or non-pancreatic origin
141
Why can pancreatic carcinoma be difficult to diagnose?
Presentation often occurs as a result of metastases rather than as a direct effect of the primary tumour
142
What diagnostic tool is used for pancreatic carcinoma?
Imaging
143
Where is vitamin B12 and bile salts absorbed?
Terminal ileum
144
Where does most of the absorption of vitamin B 12 and bile salts take place?
The duodenum and jejunum of the small intestines
Clinical Biochemistry
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