Clinical Biochemistry

Clinical Biochemistry
AASER ABDELAZIM
Professor of Biochemistry and Molecular Biology
FAIMER Fellow 2021 (Medical Education)
Consultant of Clinical Biochemistry
aaserabdelazim@yahoo.com

8/15/23 2
Aaser Abdelazim Clinical Biochemistry
Introduction to
Clinical Biochemistry

8/15/23 Aaser Abdelazim Clinical Biochemistry 3
1. Clinical biochemical tests comprise over of all
hospital laboratory investigations
2. Most biochemical tests are now performed at the site of
clinic especially during major operations like transplantation
not only in clinical biochemistry labs.
3. Most laboratories are now computerized and use:
1.The par-coding for specimens
2.Automated methods in analysis
This leads to:
A.High degrees of productivity .
B.Improves the quality of service.
C.Allow direct access to the results by clinicians.

History
Clinical examination
Diagnostic services
Imaging Physiological tests
ECG, EEG, lung functions
Lab services
Hematology Histopathology Immunology Microbiology
Clinical biochemistry
Core tests Emergency tests
Specialized tests
Place of clinical biochemistry in medicine

Core tests commonly
requested by physician
e.g., U, LFTs and Es
(Urea, liver function tests
electrolytes )
Core tests
1. Not all labs introduce
the service but it
restricted only to
some reference
centers
2. Needed to diagnose
rare diseases
Specialized tests
1. Done immediately
2. Results taken on call
3. Need to work out of
normal hours of lab.
4. All labs should
perform theses tests.
Emergency tests
Core biochemical tests
Sodium, potassium, chloride, bicarbonates
Urea, creatinine
Calcium, phosphates
Total proteins, albumins
Bilirubin, alkaline phosphatase
ALT, AST
T4, TSH
ɣ-GT, CK
Blood gases
Amylase
Specialized tests Emergency tests
Hormones Urea and electrolytes
Special proteins Blood glucose
Trace elements Blood gases
Vitamins Paracetamol
Drugs Salicylates
Lipids and lipoproteins Calcium
DNA analysis Amylase

Nutritional assessments and
diagnosis of digestive disorders
AASER ABDELAZIM
Professor of Medical Biochemistry
Zagazig University, Egypt
University of Bisha, KSA

Mal nutrition:
Definition:
qIts is a common problems among peoples in developed countries
qIt may means starvation but it had a much wider meaning (both inadequacy in
any nutrient in the diet as well as excess food intake).
qMal nutrition can be resulted from exposing the body to injuries or in major
surgical operations
•Decrease
intake
•Loss of
nutrients
Decrease
the
nutrient
store
Specific
metabolic
and
biochemical
effects
Clinical
signs and
symptoms
Consequence of mal nutrition:

Assessment of mal nutrition:
HISTORY EXAMNATION BIOCHEMICAL INVESTIGATIONS
qChange in weight
qPoor wound healing
qExposed to heavy
infections
qHistory of food and
water intake over past 7
days.
qAsking about appetite
qTypes of food intake
Examine:
qHeight
qWeight
qArm circumference
qSkin-fold thickness
qBody mass index(BMI)
BMI =
Weight (Kg)
(Height)2 meters
qProteins : but affected by
other factors e.g. liver
qBlood glucose: low and
ketosis in starvation
qLipids: fasting plasma TGs
qVitamins:
qMinerals: trace and major
elements
BMI Nutritional state
< 18.5 Underweight
18.5-24.9 Normal weight
25-29.9 Overweight
> 29.9 Obese

Lab assessment of vitamins deficiency:
Vitamin Deficiency state Lab assessments
Water soluble
Ascorbate Scurvy Plasma level
Thiamine (B1) Beri-Beri Plasma level /Transketolase activity
Riboflavin (B2) Rare single deficiency Plasma level /GRD activity
Pyridoxine (B6) Dermatitis/anemia Plasma level/AST activity
Cobalamine (B12) Pernicious anemia Serum B12/full blood count
Folate Megaloblastic anemia Serum/blood folate/ CBC
Niacin Pellagra Urinary niacin metabolites
Fat soluble
Vitamin A Blindness Serum vitamin A
Vitamin D Osteomalcia /rickets Serum 25-hydroxychalciferol
Vitamin E Anemia/ neuropathy Serum vitamin E
Vitamin K Defective clotting Prothrombin time PT

It may ranges from simple dietary supplements to total parenteral nutrition (TPN)
Spectrum of nutritional support:

Patients requirements of nutrients:
(1) ENERGY:
Harris-Benedict equation
for energy need calculation
Principle Sources Of Energy:
qCARBOHYDRATES: (4 Kcal/g)
qLIPIDS: (9 Kcal/g)
qAMINO ACIDS: (4 Kcal/g)
(2) NITROGEN:
qAmino acids provide nitrogen
and also yield energy.
qProteins should be 10-15 % of
total calories requirements
(3) VITAMINS AND TRACE ELEMENTS:
qThey called micronutrients
because they needed by minute
amount.
qRecommended Dietary
allowances (RDAs) postulate these
requirements

Average daily requirements of vitamins Average daily requirements of essential
trace elements
Average daily requirements of vitamins and essential trace elements/day:

Digestive system:
qIs a tube runs through the body.
qIts function is to prepare nutrients to be
absorbed in to blood then transported to
all tissues.
qNutrients will be digested in oral cavity,
stomach and intestine.
qSalivary, pancreatic and intestinal
secretions aid in the digestive sate.

Digestive
Disorders

MALABSORPTION
Definition: Impairment of absorptive mechanism; it can be occurred at any
stage of life form many causes. Resulting in weight loss in adults and
growth failure in children.
Causes and consequences of malabsorption:

Biochemical investigations of malabsorption
Tests identify malabsorption Tests identify pancreatic functions
1. Fecal fats test
2. Fecal microscopy
3. butterfat test
4. C14 triglycerides test
5. Xylose absorption test
1. Lundh test
2. Secretin test
3. pancreolauryl test

Tests identify malabsorption:
1) Fecal fats: presence of fatty stool; measurement of total fats in five days
collected stool.
2) Fecal microscopy: presence of fat globules
3) Butterfat test: presence of CM in patient blood after fat load indicates normal
absorption
4) C14 triglycerides test: oral load of radio-labelled C14 triolein is absorbed
and metabolized and C14 CO2 is measured in breath If present indicates
normal digestion and absorption
5) Xylose absorption test: serum measure of xylose after oral load indicates
normal absorption of monosaccharides.

Tests identify pancreatic functions:
1) Lundh test: collection of duodenal contents after meal and the activities of
pancreatic trypsin and amylase were measured.
2) Secretin test: I/V injection of secretin lead to stimulation of pancreatic
secretions which is assessed by measurement of pancreatic amylase and
trypsin in duodenal contents.
3) Pancreolauryl test: flourescein dilaurate is hydrolyzed by cholesterol
esterase in pancreatic secretions then the water soluble flourescein is
absorbed and excreted in urine while its fluorescent color indicates
• Normal absorption.
• Normal pancreatic functions

Other biochemical tests investigate malabsorption and GIT
diseases
Test Purpose
1. Urea breath test Used to identify patients with helicobacter pylori
which is strongly associated with peptic ulcer
2. Hydrogen breath test Assesses bacterial overgrowth in intestine
3. Lactose /sucrose
tolerance test
Measure functions defects in disaccharidases like
lactase and sucrase.
4. Fecal chymotrypsin/
elastase
Used to measure of pancreatic functions mainly in
cystic fibrosis.
5. Intestinal
permeability
Biologically inert polymers are used to assess
mucosal permeability by measuring their
excretion in urine after oral load.
6. Schilling test Assess vitamin B12 absorption

Gastrointestinal disease Description
(1) Inadequate digestion Seen in chronic pancreatitis due lack of pancreatic
enzymes.
(2) Inadequate intestinal mucosal
surface
Seen in coeliac disease (an autoimmune disorder of
the small intestine that occurs in genetically
predisposed people of all ages from middle
infancy onward. Symptoms include pain and
discomfort in the digestive tract, chronic
constipation and diarrhoea, failure to thrive (in
children), anaemia and fatigue, but these may
be absent.
(3) Infections of bowel Affecting the mucosa and sub mucosa or entire
bowel
(4) Abnormal bowel anatomy
(5) Insufficient bowel Occurs after removal of bowel in bowel infarction or
repeat surgery for chronic bowel disorders
(6) Malignant diseases Usually not associated except in cases associated
of abnormal bowel motility or tumors secretes
VIP
Generalized malabsorption occurs due to a lot of gastrointestinal diseases include:
GASTROINTESTINAL DISEASE

Condition Effect
Inadequate bile
salt secretion
q Occurs in many types of liver diseases and give rise to fat
malabsorption.
q Associated with Osteomalcia or rickets due to failure of
vitamin D absorption.
Vitamin B12
malabsorption
Condition associated with pernicious anemia due failure to
secrete the intrinsic factor in gastric mucosal atrophy.
Inherited
deficiencies
of intestinal
saccharidases
Due to deficiency of some enzymes that digest disaccharides
like lactase& sucrase (lactose/sucrose intolerance).
Other conditions associated with specific malabsorption

Gastrointestinal equations:
Item Equation / description
Stool osmolal
gap
Stool osmolar – (2xNa+K)
q> 100 osmotic diarrhea
q< 100 Secretory diarrhea
Fractional
excretion of
amylase
100 x (urine amylase) x (plasma creatinine) / (plasma
amylase) x (urine creatinine)
q>5% acute pancreatitis
q< 1% macro amalyasemia

Aaser M. Abdelazim
Professor of Biochemistry
LIVER FUNCTION TESTS

Liver Functions Tests
1.Functions of human liver.
2.Major tests used in diagnosis of liver
disorders.
3.Major changes in plasma enzymes and their
indication in liver diseases.
4.Major pathological changes in liver.
5.Hepatic coma.
6.Jaundice.

Functions of liver:
1.Metabolism (Lipid, Proteins,
Carbohydrates)
2.Storage (Glycogen, Vitamins, Vitamin
B12)
3.Excretory function (Bilirubin,
Cholesterol).
4.Detoxification (Phenbarbiton,
Amonia, Steroid Hormones, Benzoic)
5.Hematological function (Blood
formation, Blood volume, Blood
coagulation).
CAH: chronic active hepatitis
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Liver is the master organ in the body, it serve all other organs

Anatomical over view
Figure (1): liver Lobule

Major tests used to diagnose liver
functions
•ALT
•AST
•GGT
•ALP
•LDH
•5` nucleosidase
1. Albumin (cirrhosis)
2. (α, ᵦ, ɣ) globulins
(Cholestasis)
3. Immunoglobulins(IGs)
- IgG: chronic active
hepatitis
- IgA: portal cirrhosis
- IgM: biliray cirrhosis, viral
hepatitis
1. Anti mitochondrial .
Ab.(CAH, Biliray
cirrhosis
2. Anti nuclear:
autoimmune
hepatitis
3. Anti smooth
muscle: CAH
Plasma enzymes Plasma proteins Serology
CAH: Chronic active hepatitis

(1) Serum ALT (sGPT)(N= up to 35 U/ml)
It presents in high concentration In:
1. Liver
2. Skeletal muscles
3. Kidneys
4. Heart
Marked increase(10- 100
times)
1.Viral hepatitis
2.Toxic liver hepatitis
3.Circulatory failure
Moderate increase
1.Liver cirrhosis
2.Cholestatic jaundice
3.Liver congestion
4.Secondary to cardiac failure
5.Extensive trauma
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Major changes in plasma enzymes and its indication in
liver diseases
Causes of ALT increase

It present in high concentration In:
1.Heart
2.Liver
3.Muscle
4.Kidenys
Physiological increase
In newborn its increase
= 1.5 of normal level
Marked increase (10-
100 times )
1.Myocardial infraction
2.Viral hepatitis
3.Toxic liver cirrhosis
4.Circulatory failure due
to
-Shock
-Hypoxia
Artefacual increase
Due to hemolysis of
blood in lab.
Led to its release
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Moderate increase
1.Liver cirrhosis
2.Cholestatic jaundice
3.Liver infiltration
4.Skeletal muscle
disease
5.After trauma or surgery
(2) Serum AST (sGOT)(N= up to 40 U/ ml)
Causes of AST increase

Presents in high concentration In:
1.Bone
2.Liver
3.Kidneys
4.Lactating mammary glands
5.Intestinal wall
6.Placenta
Physiological
1.Children until
puberty 2.5 times of
adult level
2.Pregnancy
Bone diseases
1.Osteomalcia
2.Rickets
3.Bone carcinoma
4.Healing stage of bone
fractures
Liver diseases
1.Cholestatic jaundice*
2.Hepatitis
3.Cirrhosis
4.Tumors * *
5.Infiltration * *
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(3) Serum Alkaline Phosphatase (ALP) N= (50-190 U/L)
Causes of ALP increase

Presents in
1.Heart
2.Skeletal muscles
3.Liver
4.Kidneys
5.Brain
6.Malignant tissues
Marked increase
1.Myocardial infarction
2.Hematological diseases
-Leukemia
-Shock
-Pernicious anemia
Moderate increase
1.Viral hepatitis
2.Skeletal muscle
diseases
3.Pulmonary embolism
4.Infections
Artefacual increase
Hemolysis of samples
LDH isoenzymes
1.LDH1:heart, erythrocytes, blast, kidneys
2.LDH2: heart
3.LDH3:intermediate
4.LDH4:liver
5.LDH5:liver
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(4) Serum Lactate Dehydrogenase (LDH) N= (60-250
IU/L)
Causes of serum LDH increase

Presents in:
1.Liver
2.Kidneys
3.Pancreas
Liver diseases
1.Cirrhosis
2.Metastatic cancer
3.Hepatic infiltration
4.Cholestasis
Chronic alcoholism Patient with
anticonvulsant therapy
8/15/23 32
(5) Gamma Glutamyle transpeptidase (γ-GT) N= up
to 38 U/L
Causes of GGT increase

Major pathological changes in liver
Liver cell damage Cholestasis Infiltration of liver
Impaired the secretion of bile
Then accumulated in the
plasma
1. Secondary to a disease
2. Abscess
3. Parasitic emboli
As bilhariziasis cause
destruction of cells
Destruction of cell
Acute: as viral infection Chronic : Loss of function
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(1) Liver cell damage
Causes:
•Viral infection
•Toxins (alcohol, paracetamol, acetaminophen)
•Hypoxia and congestion in chronic heart failure (CHF).
•Secondary to biliray obstruction.
Biochemical effect:
1. Release of intracellular constituents into blood.
2. High sGOT (AST) and sGPT(ALT).
- Massive destruction: sudden fall after high elevation
- Chronic destruction: high level for long time
ALT than AST Means liver viral hepatitis
AST than ALT
Means excess damage,
cirrhosis, hypoxia and tumors
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Liver diseases and AST-to-ALT ratio
Disease Ratio
EtOH 1.5
Drugs 2.0
Cirrhosis 1.4-2.0
Hepatocellular carcinoma (HCC) > 1.5
Intra hepatic cholestasis > 1.5
Extra hepatic cholestasis 0.7-0.8
Acute viral hepatitis < 0.65
Acute myocardial infraction (MI) > 3.0

With jaundice (Cholestatic jaundice) With out jaundice
1. Gall stones
2. Carcinoma (obstruction
of bile duct)
1. Some forms of Viral hepatitis
2. Biliary cirrhosis
3. Drugs : phenothiazine.
1. Plasma Bilirubin increased to be 50 mg/dl
2. ALP increases
3. ALT, AST increases
4. Increase GGT
5. Increase 5` nucleotidase
1. Obstruction to only part of biliary
system
2. Cholengitis
3. Primary biliary cirrhosis
Biochemical
changes
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(2) Cholestasis
Intra hepatic
Extra hepatic

Biochemical changes:
Abscess
(1)
Amyloidosis
(2)
Tuberculosis
(3)
1. Increase synthesis in
sinusoids
2. Regarded to circulation
3. But it highest in Cholestasis
8/15/23 38
High serum ALP
High serum GGT
Normal bilirubin
ALT and AST normal or slight raised
Why?
(3) Liver infiltration
(5) Carcinoma from lung or stomach
Parasitism
(4)
CAUSES

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17.1 µmol/l bilirubin=1 mg/dl
Case study (1):
0.41 mg/dl

8/15/23 40
Casestudy (1):

1. Liver function tests indicate mild cell damage; this appeared from
normal levels of AST and Bilirubin and slight increase of ALT (38/N =
<35).
2. High serum ALP indicates one of the following:
a) Bone metastasis tumor; and this not excluded by normal level
of Ca as ALP is very high (bone scan is very important here)
b) Metastatic breast carcinoma
c) Hepatic metastatic carcinoma from breast
3. Further investigations are required
a) Bone scan
b) Tumor markers
c) Histopathological examinations
Comments on case 1
Aaser

Hepatic coma
Definition: is the occurrence of confusion, altered level of consciousness as a
result of liver failure.
Biochemical findings
High blood ammonia
qSerum ammonia levels are
elevated in 90% of patients.
qNot all hyperammonemia
(high ammonia levels) is
associated with coma.
Abnormal liver function tests
indicating liver failure

Causes: other causes with hepatic faliure may predispose coma like:
Type Cause
Excessive
nitrogen
load
1. Consumption of large amounts of protein
2. Gastrointestinal bleeding e.g. from esophageal varices (blood is high in protein, which
is reabsorbed from the bowel),
3. Renal failure (inability to excrete nitrogen-containing waste products such as urea),
4. Constipation
Electrolyte
or
metabolic
disturbance
1. Hyponatraemia (low sodium level in the blood) and hypokalaemia (low potassium
levels)—these are both common in those taking diuretics, often used for the treatment of
ascites
2. Alkalosis (decreased acid level),
3. Hypoxia (insufficient oxygen levels),
4. Dehydration
Drugs and
medications
1. Sedatives: such as benzodiazepines (often used to suppress alcohol withdrawal or
anxiety disorder),
2. Narcotics: (used as painkillers or drugs of abuse) and sedative antipsychotics, alcohol
intoxication
Infection Pneumonia, urinary tract infection, spontaneous bacterial peritonitis, other infections
Others
Surgery, progression of the liver disease, additional cause for liver damage (e.g. alcoholic
hepatitis, hepatitis A)
Unknown In 20–30% of cases, no clear cause for an attack can be found

Hepatic failure
The energy to brain cells is decreased
Due to depletion of α-ketoglutarate
(NH3)
Crosses the blood-brain barrier
(NH3)
Glutamate Glutamine
Excess Glutamine lead to
increase the osmotic pressure
in brain cells (become swollen)
Increase the activity of GABA in brain due to
conversion of α-ketoglutarate in to glutamate
(inhibitory neurotransmitter)
Brain edema (cytotoxic type)
Ammonia (NH3) accumulates in
the systemic circulation

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1. Definition of jaundice
2. Bilirubin metabolism
3. Causes of jaundice
4. Differential diagnosis of jaundice

1) Is a yellow discoloration of skin or/and sclera due to high
concentration of plasma Bilirubin over 40 µmol/l
2) Normal plasma total bilirubin is less than 22 µmol/l (3-15
µmol/l OR 0.3 -1 mg/dl )
3) Normal conjugated = 0.1 mg/dl
1. See bilirubin metabolism figure (3)
2. Main causes of high bilirubin are three
figure (4)
• Hemolysis
• Failure of conjugation mechanism in
liver
• Obstruction in biliary system
17.1 µmol/l bilirubin=1 mg/dl
Jaundice
qIndicates an elevated level of
serum bilirubin .
qIn neonates it is important to
determine the concentration of
Unconjugated bilirubin in order to
decide the treatment required
qIn adults most common type is
due obstruction.

Figure (2) Bilirubin metabolism
Water soluble
•Non water soluble (not secreted
from kidneys)
•It is neurotoxic
•Can cause permanent brain
damage in neonates
•Brown coloration of feces
•If not present lead to pale
colored feces
Bacteria
Orange color of urine on
long standing

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Figure (3): Causes of jaundice

Hemolysis
Plasma
Unconjugated
bilirubin
Main in neonates
>> 200 µmol/l (12
mg/dl); need
phototherapy
>> 300 µmol/l(17
mg/dl); need
exchange transfusion
Extra hepatic obstruction
Both Plasma
bilirubin and
ALP
Little or no
urobilinogen in
urine
Pale stool
Partial
Complete
ALP with
bilirubin within
reference range
Level of ALP
indicate the
degree of
obstruction
Hepatocellular damage
Both Plasma
bilirubin and
ALP with ALT
and AST
Obstruction occurs
here secondary to
hepatic cell
damage by toxins
or infection
conjugated
Indicates
damage of
liver cells
Little or no
Stercobilinogen
in intestine

Laboratory differential diagnosis of jaundice
Feature Hemolytic Cholestatic Hepatocellular
Serum Bilirubin
>75 µmol/l (4.38 mg/dl)
(Unconjugated)
(Indirect)
Over 3 times than in
hemolytic
(Conjugated) (Direct)
>75 µmol/l but later
(Unconjugated/conjugated)
Conjugated increased when
obstruction occurs later on
Bilirubin in urine
Not present
(Unconjugated is not water
soluble and bound to albumin
and not filtered )
Present Present
(high level of conjugated bilirubin)
Urine
Urobilinogen
Increased Decreased /absent Decreased/absent
Stool Normal
Clay/pale in color
(no bilirubin reaches the
intestine)
Normal
Reticulocytosis + - -
Hemoglobin
/Haptoglobin Decrease Normal Normal
Plasma enzymes LDH may increased
1. ALP over 3 times the
reference range it act
as a mirror for the
degree of obstruction.
2. High AST, ALT, GGT
and LDH
High ALP but appear later
High ALT and AST
Due to hepatocytes damage

Neonatal jaundice
Causes:
1.Inability of immature liver of neonates to produce UDPG- transferase
2.Higher turnover of neonatal erythrocytes shortly after birth to replace fetal HbF
with normal HbA
Neonatal jaundice
Transient
Physiological jaundice of the
newborn (PJN)
Sustained
1. Hemolytic diseases
2. Biliray artesia (post
hepatic type)
3. Idiopathic neonatal
hepatitis (rare) (hepatic
jaundice)
1. Blood groups
incompatibility
between mother and
fetus (+ direct anti-
globulin)
2. Absorption of large
hematoma.

Blood cells of mother Blood cells of fetus
Both come in contact
1. Through transfusion
2. Or during pregnancy
Immune system of
mother recognized
them as foreigners
Produce antibodies
against them
RBCs destruction
This usually not
affects the 1st
child but affects
the second one
Mechanism of neonatal jaundice
Aaser
Group (O) or
RH-
Group (A/B) or
Rh+
1. High amounts of IgM (anti-A, anti-B)
2. Small amounts of IgG (anti-A, anti-B)

Consequence of neonatal jaundice
Treatment
Phototherapy if the level exceed 10 mg/dl
Source of light emitted light of 450 nm
Unconjugated
bilirubin
(insoluble)
Soluble bilirubin
Kernicterus
Brain cell nuclei stained yellow
Damaged due to high
bilirubin can cross blood
brain barrier (not occurs in adults
why?! Here type of bilirubin is unconjugated
which is water insoluble).
Usually brain is damaged if
the level reaches > 20
mg/dl
cerebral palsy, deafness,
mental retradation

Physiological jaundice of the newborn (PJN)
Transient condition/ phenomena in which
bilirubin subsides within few weeks
Other factors affecting neonatal hyperbilirubinemia
1.Decrease binding of Unconjugated bilirubin to albumin
2.reabsorption of intestinal meconium
3.constituents in mother’s milk. Progesterone and other hormones in
breast milk as well as beta-glucuronidase may suppress neonatal
conjugation of bilirubin
1. Increase total and Unconjugated bilirubin
2. Near-normal conjugated bilirubin
3. Normal hepatic enzymes if there is no iflammation
Physiological jaundice of the newborn (PJN)

8/15/23 55
Case study (2):

8/15/23 56
Case study (2):

Aaser M. Abdelazim
KIDNEY FUNCTION TESTS

8/15/23 59
1. Anatomical view of the kidneys and
nephrons.
2. Functions of kidneys
3. Renal functions tests
4. Glomerular function tests
5. Tubular function tests
6. Renal disorders
7. Renal failure
RENAL function tests

Fig (1): Kidney anatomy
Anatomical view of human kidney

Fig (2): Nephron
Nephron structure

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8/15/23 63
Endocrine links in kidneys

Renal function tests
Glomerular function Tubular function
(1) Urine examination (see the practical part)
(2) BUN
(3) Serum Creatinine
(4) Creatinine clearance
(5) Urea clearance
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Urine concentration test
Vasopressin test
Urine dilution test
Plasma electrolytes
Maximal tubular reabsorption of glucose and
secretion of Para Amino Hippuric acid (PAH )

Blood urea nitrogen (BUN)
8/15/23 65
Proteins
Liver
Urine
Urea MW= 60.06
60 gm urea contains 28 gm N
BUN= UNx28/60
Blood
Ammonia
(Toxic)
Urea
Urea
Amino acids
•Urea mainly come from metabolism of proteins
•It is a save product of ammonia (urea cycle)
•Secreted in urine (N= 20-40 gm /day)
•Normal plasma level= 20-40 mg/dl

Increased in:
ØChronic renal failure
ØDecrease renal perfusion (CHF)
ØRenal tract obstruction (stones,
tumors)
ØNephritis
ØAfferent arteriole vasoconstriction
ØHigh protein diet
ØGastrointestinal bleeding
ØDehydration
ØDrugs
-Amino glycosides
-Diuretics
-Lithium
-Corticosteroids
Decreased in:
ØMal nutrition
ØLiver diseases
ØLow protein diet
ØRenal dialysis
ØOver hydration
ØThird trimester of pregnancy

Normal serum = men: 0.8-1.3 mg/dl , women: 0.6-1.0
mg/dl or (60-120 µmol/l)
Creatinine is best used to urea for assessment of
renal functions:
• Not affected by diet
• Non-threshold i.e. Completely execrated in urine not reabsorbed from
tubules
• Mainly of endogenous origin
• Creatinine is mainly excreted from kidneys while 75% only from urea are
excreted in kidneys and 25% in colon.
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Creatinine MW= 113.12 g/mol
Serum creatinine

8/15/23 69

Increased in :
• Renal failure
• Decrease renal perfusion due to (CHF)
• Renal obstruction
• Acute tubular necrosis
• Glomerulonephritis
• Hypothyroidism
• Skeletal muscle trauma
• Ketonemia (diabetic ketoacidosis)
• Diabetic nephropathy
• Rhabdomyolosis
• Eclampsia and pre-eclampsia
• Creatine supplement
• Dehydration
• Drugs
Hydantion: tranqulizer, Cephalosporins
,Aminoglycosides, Diuretics, methyldopa:
parkinsonism Cemetidine , trimethoprim
Decreased in:
•Amputations
•Low muscle mass
•Muscular dystrophy
•Myasthenia gravis
•Pregnancy
Abnormalities of Serum Creatinine
One mg/dl of creatinine is 88.4 μmol/l.

CKD according to creatinine levels
kidney disease is divided into five stages according to creatinine level.
CKD stage
1 2 3 4 5
Cr level
(mg/dl)
<1.6 1.6-2 2.1-5 5.1-7.9 >8
A. Peoples with creatinine levels >2 mg/dl should take their treatments as soon as
possible.
B. Usually stage 1 indicate mild impairment of kidney functions and need only
some changes in routine
1. Change the diet routine (take egg white-lean meat-fruits)
2. Increase the exercise
3. Depend on the natural food and plants to lower the creatinine.

Creatinine coefficient
•The amount of Creatinine excreted in
urine/ kg BWt/ day
•N= 1.5 gm /day in male and 1.0
gm/day for female
•Depends on:-
1.Body muscle mass
2.Body conditions
8/15/23 72

Creatinine clearance
Biochemical indications:
• Assess renal glomerular function
• Drug monitoring
• Advanced stages of renal failure
Amount of Creatinine filtered = the amount of Creatinine excreted
GFR x Cr conc. In Plasma = Cr conc. In urine x urine Volume
GFR (C) x P = U x V
U x V
P
C (Cr clearance) =
mg/dl x ml/ min /mg/dl = ml / min
Comments the Normal levels =107-139 in male and 87-107 in females.
Levels less 90ml/min indicate bad.

Creatinine clearance test
It is two part test ; 24-hour urine collection and blood samples are measured

Increased :
1.Pregnancy
2.Exercise
3.Drugs;
qAminoglycosides,
q Cimetidine,
qCisplatin.
Decreased:
1.Renal insufficiency
2.Acute tubular necrosis
3.Congestive heart failure
4.Renal artery atherosclerosis
5.Advanced age: decreased by 1 ml / min
after 30 years
6.Inadequate urine specimens
7.Medications:
q-Cimetidine
q-Procainamide : anthesia
q-Trimethoprim
q-Antibiotics
q-Quinidinine
8/15/23 75

8/15/23 77
Case study (1)

Mw of Creatinine = 113.12 g/mol
To convert from µmol/l to mg/dl divide on 88.4
Urine volume/ minute (V) =
Urine /day
24x60
=
2160
1440
= 1.5 ml/minute
P= 150 µmole of Creatinine in plasma = 1.33 mg/dl
U= 7.5 mmole of Creatinine in urine = 66.3 mg/dl
Creatinine clearance =
UxV
P
66.3 x1.5
1.33
= 74.7 ml/minute !
=
This level indicates low flow rate its normal is (107-139 ml/minute)
Case study (1)
After correction of that urine is collected after 17 hours only the Cr Cl
become 105 ml / minute this indicate normal flow rate
Aaser

(2) Tubular functions tests:
Test:
1.Allow patient to take water after 6 pm but no food.
2.Come to lab at 7am,
3.Take urine samples at 7(zero time), 8, 9 am
Results
Any of these samples its Sp Gr should be more 1026 indicates good renal function
With in 1020 minor renal failure
1010-1015 : severe renal damage
8/15/23 79
Contra indication:
1)High blood urea
2)Patients with clinical signs of RF
Uses:
Used for testing the renal concentration ability in response to water deprivation
Can assess :
ØNormal ADH
ØNormal response of DCT to ADH.
(1) Urine concentration test (water deprivation test):

(2) Vasopressin test:
Test
1.At 8 pm patient take 5 units of vasopressin tanate.S/C
2.Collect urine at 7, 8, 9 am
3.Sp gr should be more 1020 : good renal function
(3) Urine dilution test (water load test):
1. Water not allowed to patient over night
2. Come at mooring to lab
3. Take 1000 ml water to drink completely
4. Collect 4 urine samples one hour interval after drinking
Results :
q Normal urine led down in 4 hrs is 700 ml at least
q Sp gr. Of one of the 4 at least = 1004
q Severe damaged kidneys secrets urine with sp gr not less than 1010
and volume not mor than 400 ml
Contra indications of water load test
•Odema
•Hyponatremia
•Renal failure with water intoxication
8/15/23 80

8/15/23 81
(4) Tubular maximum of glucose reabsorption and
PAH secretion
TmG =GFR x Pg – Ug x V
Amount of glucose reabsorbed = amount of glucose filtered – amount
of glucose secreted
TmPAH = UPAH x V – GFR x PPAH
Para amino hippuric acid (PAH) actively excreted = PAH filtered- PAH
absorbed
N = 350±75 minutes

8/15/23 82
Glucose MW=180.16 g/mol
Case study (2)

8/15/23 83
Case study (2) interpretation

Notes on the report
1.High Na level =150 mmol/l (N= 136-145 mmol/l).
2.High BUN = 91.6 mg/dl (N= 20-40 mg/dl)
3.Normal creatinine level= 0.71 mg/dl (N= 0.6-1.2 mg/dl)
4.Normal blood glucose = 97.2 mg/dl (N=120-130 mg/dl)
Comments on Case study (2)
MW of Urea = 60.06 g/mol
Water deprivation test in this case is dangerous!!
It is contra indicted in patients with high BUN and Na levels
History and high urine volume with normal blood glucose indicate
diabetes insipidus
So no need for further tests except ADH level mointoring and radiology like
CT or MRI for confirmation
The main cause of thirst, is her hyppernatremia and high water loss (polyurea)
Aaser

BUN-to-creatinine ratio
1-
2-
3-
1-
2-
3-
4-

1. Causes of glomerular dysfunctions
2. Biochemical changes in glomerular dysfunctions
3. Causes of tubular dysfunctions
4. Biochemical changes in tubular dysfunctions
5. Picture of acute renal failure
6. Picture of chronic renal failure
Biochemical changes in renal diseases

The end results of renal diseases is the disturbance in nephron functions
Glomerular dysfunctions Tubular dysfunctions
1. Congestive heart failure
2. Acute/chronic glomerulonephritis
3. Acute renal fauilure
4. Low systemic blood
pressure(hemorrahge/dehydration
/shock)
5. Any disease in glomerulus
6. Renal circulatory shortage
1. Acute tubular necrosis
2. Prolonged renal circulatory
shortage
3. Progressive tubular damage due
to:
• High blood calcium
• Hyperuricemia
• Hyperkalemia
• Galactosemia
• Poisons as heavy metals toxicity

Biochemical changes in Glomerular dysfunctions
In plasma
Uremia
Hypocalcemia
Hyperkalemia Acidosis
Hyperphosphatemia
1. Increase plasma
urea/creatinine
2. Reduced the k
secretion
Low blood Na due
to high blood K
Na
K
H
H
Due to failure of
vitamin D activation
Acidosis
1
4
3
2
5
1. Decrease GFR
2. Acidosis
Due to failure of
vitamin D activation

In urine
Low urine
led down
(Oligurea)
Low urea/creatinine
Low uric acid/K
As a logic picture of plasma
Biochemical changes in Glomerular dysfunctions

Biochemical changes in tubular dysfunctions
• Reduction of water
reabsorbtion
• Failure to secret H
and reabsorb HCO3
Large volume of
dilute urine
/acidosis
• Impaired Na/K
reabsorption
Potassium
depletion(hypo K)
Hypo P/ normal
urea
• Generalized
amino acid urea
• Low blood uric
acid/P
Acquired fanconi
syndrome
1. Low specific gravity
2. Polyurea
3. Low urea
4. High Na Urine

Items Glomerular dysfunction Tubular dysfunctions
Plasma urea Uremia Normal urea
Plasma creatinine High creatinine Normal
Plasma potassium Hyperkalemia Hypokalemia
Plasma sodium Hyponatremia Hyponatremia
Acidosis Acidosis Acidosis
Plasma calcium Hypocalcaemia Hypocalcaemia
Plasma phosphate Hyperphosphatemia Hypophosphatemia
Plasma uric acid Hyperuricemia Hypouricemia
Urine volume Oligurea Polyurea
Biochemical findings in glomerular and tubular dysfunctions:

Renal failure
Acute renal failure Chronic renal failure
Postrenal
Renal
Prerenal
1. Decrease renal circulation
2. Low blood volume
3. Decrease fluid volume
reaching to the kidneys
Urinary obstructions
• Stones
• Tumors
Tubular necrosis
then glomerulus
affected later on
1. Immunologic damage as
systemic lupus erythematosus
2. No immune damage
• Multiple meloma
• Diabetic nephropathy

Biochemical changes in acute renal failure
Oliguric phase Diuretic phase
1. Decrease Na in blood
2. increase fractional
excretion of Na (FENa)
3. GFR<20 ml/min

A biochemical course of a typical patient with acute renal failure

20 ml/min X 100%
40 ml/min
FENa1
Na clearance X 100%
= = = 0.5%
Decrease renal
blood flow
200 ml/min X 100%
40 ml/min
FENa2
Na clearance X 100%
= = 5% Kidney damage

Plasma osmolality

(A man aged 40 years old presenting with lion pain has a serum
creatinine of 2.5 mg/dl, 24-houred collected urine equals 2160 ml
and found to have urine creatinine level equals 66.4 mg/dl, serum
urea 80 mg/dl, serum sodium 140 mmol/l, urine sodium 700mmol/l
and serum glucose 130 mg/dl).
1. Calculate creatinine clearance (CrCl).
2. Comment on your calculated CrCl and mention the TWO conditions
that lead to this case?
3. Calculate fractional excretion of sodium (FENa) and serum
osmolality and interpret the results.
4. If an error in timed collected urine was subsequently reported, and
the actual collection time was 12 hours only. How does this affect
the results?
Case study (3)

Biochemical changes in chronic renal failure
Generalized disease of nephrone
1. Chronic glomerulonephritis
2. Polycystic kidney
Similar to

Biochemical finding in chronic renal failure
Osmotic polyurea marked at night
Metabolic acidosis(retention of PO4, SO4 and
organic acids)/ failure of kidneys to secrete H
Impaired glucose tolerance
High blood urea/ creatinine/ marked fall in
creatinine clearance
High plasma amylase?
Hypocalcemia /hyperkalemia if there is oligurea
due to excess loss of Na and Cl
Low concentration power of kidneys
Protein urea (not more than 5 gm/day)
1
4
3
2
8
7
6
5

Consequences of CRF

The biochemical course of a typical patient with CRF before/after hemdialysis

How hypocalcaemia and secondary hyperparathyroidism develop in renal disease

Biochemical finding in acute glomerulonephritis
Oligurea
Hematurea (smoky urine due to acute inflammation/
high blood vessels damage)
Proteinurea (5-10 gm/day)
Odema (Na& water retention)/ capillary damage
and increase permeability
Low creatinine clearance
Low plasma proteins due to hemedulition
1
4
3
2
6
5

Hepatorenal syndrome
oAcute renal failure with advanced liver disease this may be due to
•Liver cirrhosis
•Metastatic tumors
•Alcoholism (inducing sever hepatitis).
oThe condition characterized by:
•Oliguria.
•Benign urine sediment.
•Low sodium excretion.
•Progressive rise in plasma creatinine.
•Reduction in GFR usually masked.
PROGNOSIS: bad unless improves the liver functions.

Continue ……

Diagnosis of heart
disorders
Aaser M. Abdelazim,

MYOCARDIAL INFARCTION (MI)
Definition: also known coronary thrombosis, most common of mortality and
morbidity in adults, diagnosed from chest pain and elevated heart enzymes.
It occurs due to narrowing of arteries supply cardiac muscles, inducing chest
pain (angina pectoris).

DIAGNOSIS OF HEART DISORDERS:
1. History: Chest pain
2. ECG: Changes indicates the severity and the site of infraction
3. Biochemical tests:
q Testing the heart enzymes CK, LDH, AST
q Other biochemical indicators: Myoglobin, Troponin I& T and lipid profile.
(a) (b) (c)
(a) Normal ECG (b) 2 hrs after the
onset of chest pain
elevated ST
segment
(c) 24 hrs after the
onset of chest pain
further episode of
chest pain

HEART ENZYMES:
Enzymes Characteristics
(1) Total CK
qTotal CK: is released from all types of damaged muscle cells
including the cardiac muscles.
qIs the 2nd enzyme released and reaches its peak within 24-48 hrs
from the onset the heart attack.
(2) CK-MB
qIt is a strong marker for early confirmation of heart infraction.
qIt is the 1st enzyme raised (6 hrs after the incident)
qUsed in post-operative patients for suspected myocardial
infraction, as it only increased in myocardial infraction.
qIt is indicated in the second infraction within few days of the 1st
one.
(3) AST and ALT
qThese enzymes are not highly specific for heart
qThey also elevated in liver, lung, muscles disorders
qAST is more present in heart than any other tissues.
qAST reaches its peak after 48 hours.
(4) LDH
qTotal LDH is nonspecific for heart.
qIt elevated in other liver, RBCs disorders.
qIsoenzymes LDH1, 2 are specific for heart.
qThey reach the peak within 4 days from the heart attack.

Enzyme
Start of rise
(hrs)
Peak
(hrs)
Duration of rise
(hrs)
CK-MB 3-8 12-24 1.5-3
CK total 4-8 24-48 3-6
AST 6-8 24-48 3-6
LDH1,2 12-24 48-72 6-12
Pattern of cardiac enzymes in the episode of myocardial
infraction:
Note that:
1) All enzymes may be appeared normal in patient plasma until 4 hrs after the
infraction.
2) The level of the enzymes in plasma correlates with the infraction size.
3) Very high levels may indicate myocardial necrosis.

2 4 6 8
0x
5x
2x
4x
1x
3x
6x
7x
LDH
AST
CK
ALT
On admission all the
results within the
reference range
Fold
increase
above
the
upper
limit
of
reference
range
Enzymes in plasma after uncomplicated MI
Duration in days

Indicator Characteristics
(1) Myoglobin
qIs the absolute first marker for MI
qStarted to be elevated in patients serum after 1-3 hrs from
the onset of chest pain.
qIt is very useful for the early detection of MI in patients in
emergency department.
Troponin I & T
It forms Troponin complex with
troponin C
qAre specific markers for acute MI.
qThey released form damaged cardiac muscles within 3-8
hrs from infraction, but they remain elevated for much longer.
q Troponin T takes about 2 weeks to return to normal level;
while Troponin I takes 5-10 days only.
q Normal level of Troponin T = 0-0.1 µg/L; Troponin I =(1-
3µg/L)
Other Biochemical inductors for MI:
Conditions predispose MI are; Diabetes Mellitus, Smoking, Hyperlipidemia, Hypertension

Parameters Characteristics
(1)Plasma appearance
qGive indication about the level of TAGs in blood.
qClear plasma indicates TAGs lower than 200 mg/dl.
qTurbid plasma indicates TAGs levels with in 300 mg/dl.
qCloudy to opaque plasma indicates TAGs over 600 mg/dl.
qCreamy layer appeared on the surface of the plasma within
4 hours indicates the presence of CM.
(2) Serum total cholesterol
qNormal serum levels equal (130-220 mg/dl).
qUsed to monitor chronic heart disease.
(3) Serum HDL-cholesterol
qLevels over 60 mg/dl are good indicator about negative
heart disorders.
qEvery 1 mg/dl decrease in HDL increases the risk of CHD
by 2-3%.
(4) Serum LDL-cholesterol
qHigh levels are bad indicator for CHD.
(5) Serum
Triacylglycerides
qTGs are not strong predictors for atherosclerosis and CHD
(6) Risk factor for CHD
qEquals the total cholesterol/ HDL-cholesterol
qLow risk (3.3-4.4).
qAverage risk (4.4-7.1).
qModerate risk (7.1-11).
qHigh risk (over 11).
Lipid profile:

Case study

Case study comments

Aaser M. Abdelazim, PhD
DIAGNOSIS OF
BONE DISORDERS

Bone disorders not imply hypocalcaemia or hyperclacemia, conversely sever
bone diseases can occur whilst blood calcium is quite normal.
Bone metabolism:
Osteocyte
Bone trabecula
Osteoblast
Osteoclast
qBone is continuously broken and reformed this called
(bone remodeling).
qOsteoclast cells are responsible for bone resorption .
Hydroxproline is a good markers for collagen
breakdown and so for bone resoption.
qOsteoblast cells are responsible for bone formation.
qOsteoblasts have high activity of ALP
qOsteocalcin is a good marker for bone ossification
and osteoblast activity.
Common bone diseases are:
qOsteoporosis
qOsteomalcia and rickets
qPaget’s disease: irregular bone resorption and formation

Disorders Biochemical markers
(1) Bone metastasis qCalcium not indicative (high, low or normal).
qPhosphate also not indicative.
qPTH low
qALP high/normal
(2) Osteomalcia, rickets qLow calcium
qHigh PTH
q25-hydroxycholecalciferol low
(3) Paget’s disease qCalcium is normal
qALP is grossly elevated
qHydroxy proline is high
(4) Osteoporosis qBiochemistry not indicative
qCalcium level unaffected
qALP is high
(5) Renal Osteodystrophy qLow calcium
qVery high PTH
(6) Ostitis fibrosa cystica
(primary
hyperparathyrodism)
qHigh calcium
qLow / normal phosphate
qHigh PTH
Diagnosis of bone disorders:

Case study

Normal ALP= 50-190 U/L
Case study comments

CENTRAL NERVOUS SYSTEM
Neurology laboratory tests

qThe central nervous system consists of the brain, spinal cord, and neuron
processes.
qThe central nervous system is surrounded by membranes of the meninges.
qThe outer covering is a thick membrane consisting mostly of collagen.
qThe ventricles or chambers produce the cerebrospinal fluid, which circulates to
the subarachnoid space where it cushions and feeds the brain.
qThis clear fluid, with a volume of approximately 100 ml, exchanges chemicals
with blood to feed the cells of the nervous system and carry away waste products.
CENTRAL NERVOUS SYSTEM
Metabolic view of brain:
1) The brain directs most metabolic processes in the body.
2) Brain cells are not energy producers, but have a constant need for energy.
3) Under normal conditions, the brain uses glucose as its sole source of energy.
When glucose levels are low, the brain can use some ketones as energy
sources.
Chemical analysis of CSF
qChemical analysis of cerebrospinal fluid provides information about trauma,
infection, and demyelinating diseases.
qMost commonly, glucose and total protein are measured in spinal fluid. However,
laboratory tests for lactate, immunoglobulin proteins, and other biochemicals are
available (see the following table).

Test Normal value Description
CSF cell count < 5 cells/mm3 qGood indicator for acute inflammatory conditions for CNS
qAbout 70% of WBCs in CNS are Lymphocytes
qMonocytes represent 30%
qDuring pleocytosis ; WBCs significantly increased.
CSF Chloride 700-750 mg/dL Decrease the value is an indicator for meningitis
CSF Glucose 50-75 mg/dL qIncreased in hyperglycemia
qDecreased in:
Bacterial infection, CNS inflammations, chemical meningitis,
hypoglycemia, subarachnoid hemorrhage.
Blood glucose more reduced in bacterial than viral meningitis.
CSF color Clear qRed color: indicates bleeding
qCloudy: in high WBCs count, high proteins and melanoma
qYellow: hyperbilirubinemia
CSF Glutamine 6-15 mg/dL Increase in hepatic coma, hepatic encephalopathy, liver failure,
Reye syndrome.
This test will be done for patients if there is a coma with
unknown origin.
CSF IgG index
IgG Index
IgG(CSF)/IgG(Serum)
0.29-0.59 High level of IgG in CSF indicates damage of blood-CNS barrier
Increase in chronic CNS infection, systemic lupus
erythematosus (SLE), multiple sclerosis, neurosyphilis, viral
infection.
CSF LDH < 40 U/L High level indicates; bacterial meningitis, CNS leukemia, stroke.
Neurology laboratory tests

Test (continue ) Normal Description
CSF Lactic acid 10-25 mg/dL qThe test examine the degree of oxygen deprivation in brain
tissue.
qHigh levels indicate; bacterial meningitis , fungal meningitis or
any states increase anaerobic brain metabolism.
Opening pressure 70-200 mmH2O qNormal CSF pressure should be less than 200 mmH2O.
qHigh CSF pressure indicates also high ICP.
qThe pressure should be measured before obtain the samples.
qHigh pressure indicates; bacterial infection, fungal infection,
T.B, tumors, hemorrhage.
CSF Total Proteins 15-45 mg/dL qHigh levels are a good indicator for brain damage.
qIncreased in; intra cranial hemorrhage, malignancies,
infections, multiple sclerosis.
CSF Pyruvate 0.5-1.5 mg/dL Low pyruvate indicates; chronic hemolytic anemia, metabolic
liver diseases, myelodysplastic syndromes, PK deficiency,
sidropastic anemia.
WBCs CSF < 5 WBCs/ mm3 qBacterial infection (>1000 cells)
qFungal infection (variable)
qViral infection (< 100 cells)
sBPP CSF (soluble
Beta proteins
precursors).
> 450 U/L qUsed mainly to detects Alzheimer disease
qLow levels indicates Alzheimer
VDRL CSF Non reactive qThis test is specific test for neurosyphilis.
qFalse positive results can obtained if there is a blood, protein,
autoimmune disorders,

Assessment of
Respiratory Disorders
Aaser M. Abdelazim

INTRODUCTION
RESPIRATION
(1) Pulmonary ventilation
(2) External respiration
(3) Respiratory gas transport
(4) Internal respiration
Breathing: means
movement of air In and
Out of the body
Oxygen loading and
carbon dioxide loading
Transportation of gases
by blood stream
Exchange between
capillary and body cells.

(1) BREATHING (PULMONARY VENTILATION)
(A) Inspiration: Diaphragm flattens creates a vacuum pulling air into the lungs
(B) Expiration: Muscles relax and push air out of the lungs

RESPIRATORY VOLUMES AND CAPACITIES
Volume Definition
Tidal Volume (TV) Volume of air moved into and out of the lungs each
breath
Inspiratory reserve
volume (IRV)
Amount of air you can forcibly be taken in
Expiratory reserve
volume (ERV)
Amount of air that can be forcibly expelled
Residual Volume Air that cannot be expelled from the lungs
Vital capacity (VC) Total amount of exchangeable air TV + IRV + ERV
Dead Space volume The amount of air that doesn’t make it to the lungs in
a breath.

(2) EXTERNAL RESPIRATION
qGas exchange at the lungs
qOxygen into blood and CO2 removed from blood

(3) GAS TRANSPORT IN THE BLOOD
q Oxygen forms oxyhemoglobin with
hemoglobin molecules.
q CO2 in transported via bicarbonate in
plasma.

(4) INTERNAL RESPIRATION
qExchange of gases between blood
and tissue cells.
qOxygen unloaded and CO2 loaded.

Terms Description
Hypoxia qInadequate supply of oxygen to the body tissues
qCauses skin to become cyanotic
Carbon Monoxide
Poisoning
CO binds to the binding site that oxygen binds to on hemoglobin
preventing gas transport of oxygen
Hyperventilation Body’s reaction to increased levels of carbon dioxide or acids in
blood.
Respiratory terms qEupnea: normal respiratory rate.
qHyperpnea: Increased respiratory rate (exercising)
qApnea: stopped breathing.
qDyspnea: difficult breathing.
SOME TERMS:

Arterial blood gases (ABGs):
Collection and handling of arterial blood gases:
1) The specimen for blood gases and pH should be arterial or arterialized
capillary blood
2) All air bubbles should be removed.
3) Air contamination will reduce the CO2 and increases the O2 in the sample due
to the difference in the PO2 and PCO2 tension of these gases in the
atmosphere.
4) Use the correct amount of heparin (0.05 mg heparin/ml blood).
5) The specimen must be placed in ice water until analysis or examined
immediately.

Calculations in blood gas analysis:
pH = 6.1 + log HCO3 /(PCO2 x 0.0301)
Given arterial pH and PCO2, the formula to solve for bicarbonate is derived as follows:
For example, calculate HCO3 given pH 7.50 and PCO2 of 30 mm Hg.
7.50 = 6.1 + log [HCO3 /(30 x 0.0301)]
7.50 = 6.1 + log (HCO3/0.9)
1.4 = log (HCO3 /0.9)
inv. log 1.4 = (HCO3 /0.9)
25 = (HCO3 /0.9)
25 X 0.9 = HCO3 = 23 mmol/L

Venous Versus Arterial Samples:
There are five main evaluations we need to consider in interpreting ABGs in the
clinical setting:
1)Acid-base status
2)Alveolar ventilation
3)Oxygenation status
4)O2 transport
5)Carboxyhemoglobin

ACID-BASE STATUS
(1) Metabolic Acid-Base Disturbances:
Metabolic acidosis Metabolic alkalosis
qDiabetic ketoacidosis qVomiting
qUremia qGastric suction
qRenal tubular acidosis qLow potassium or chloride level
qLactic acidosis qLiver cirrhosis with ascites
qGIT loss of HCO3 , fluids and
potassium
qCorticoid excess (Mineralocorticoids)
qToxins qMassive blood transfusion
qHypertension due to dehydration qHigh doses of alkalis in acidosis

(2) Respiratory Acid-Base Disturbances:
Respiratory acidosis Respiratory alkalosis
qPneumonia qHyperventilation due to high altitudes
qEmphysema qFever
qAsphyxia qSalicylates poisoning
qBronchial asthma qEncephalitis
qMorphine poisoning qHysterical

APPROACH TO INTERPRETING ACID-BASE DISTURBANCE:
In order to interpret acid-base disturbances, the following five factors are considered:
1. pH
2. HCO3–
3. PCO2
4. Anion gap
5. Assessment for compensation
qVentilation and PCO2 relationship
oVentilation is inversely proportional to the resulting PCO2.
oVentilation increases in response to a drop in plasma and cerebrospinal fluid
(CSF) pH detected by the respiratory center in the medulla.
oLikewise, the kidneys compensate for a primary respiratory defect. The respiratory
system can never completely compensate for a metabolic defect, but renal
compensation can almost be complete.

qSteps for determination of acid base disturbances:
Steps Interoperation
1) Determine if the patient is acidemic or
alkalemic, based on pH.
Normal pH 7.4±0.03
2) The primary disorder is determined by
evaluating HCO3– and PCO2
1. If HCO3– is elevated and pH is elevated, there
is metabolic alkalosis.
2. If both are decreased, there is metabolic
acidosis.
3. If HCO3– is within the normal reference range
and PCO2 is elevated but the patient is
acidotic, the condition is respiratory acidosis.
4. If bicarbonate is within the normal reference
range and PCO2 is decreased but the patient
is alkalotic, the condition is respiratory
alkalosis.
3) Determine the anion gap from the formula
Anion gap= (Na+K)-(Cl+HCO3) or (Na)-(Cl+HCO3)
So anion gap is the difference between cations and
anions in the blood Normal = 10-20 mmol/L and
without K = 6-15 mmol/L
In metabolic acidosis and mixed acid-base
disorders, the anion gap is significantly elevated.
4) pH, HCO3–, and PCO2 are considered to
determine if compensation is as expected based
on the typical ratio of 20:1 for bicarbonate to
carbonic acid.
1. both decreased HCO3– and PCO2 should
produce a slightly decreased or nearly normal
pH if they are in metabolic acidosis
compensation.

Steps Interoperation
4) pH, HCO3–, and PCO2 are considered to
determine if compensation is as expected based
on the typical ratio of 20:1 for bicarbonate to
carbonic acid. ...........(Continued)
2. To determine the actual ratio of bicarbonate to
carbonic acid, PCO2 is converted to H2CO3
using the relationship PCO2 X0.03 =H2CO3
3. Metabolic acidosis with a normal anion gap
is associated with:
A. renal diseases such as proximal or distal
renal tubular acidosis,
B. Renal insufficiency with HCO3– loss,
C. Hypoaldosteronism with potassium-sparing
diuretics.
D. Other causes include loss of alkali due to
diarrhea or ureterosigmoidostomy or ingestion
of carbonic anhydrase inhibitors, such as the
medications used to treat glaucoma.
4. Metabolic acidosis with a high anion gap is
generally due to:
A. Addition of acid from ketoacidosis;
B. Lactic acidosis from hypoperfusion or
decreased circulation
C. Toxic ingestions of aspirin, ethylene glycol, or
methanol.
D. Renal insufficiency.
Compensation for metabolic acidosis or alkalosis is achieved initially by the
respiratory system. How?!

RESPIRATORY DISORDERS
Disorders Diagnosis
Chronic bronchitis These patients have chronic hypoxia, as indicated
by low SO2 and PO2, and CO2 retention, as
indicated by increased bicarbonate and PCO2.
Fetal Lung Maturity 1. Immature fetal lung resulted from the decrease
in the lung surfactant (phosphatidyl choline,).
2. It occurs to premature babies (< 37 weeks) or
weight < 2500 g.
3. causing decreased oxygenation of the
collapsed alveoli and cyanosis and respiratory
distress in the neonate
Respiratory Distress Syndrome (RDS) The arterial blood gases initially indicate
1.Very low PO2,
2.Normal or low PCO2, and
3.Elevated pH causing respiratory alkalosis.

ALCOHOL
Aaser M. Abdelazim

ALCOHOL
qAlcohol is a drug with no receptors.
qIts effect on the cells and organs is not understood.
qFor clinical purposes alcohol is calculated in units (One unit = 200-300 mmol of ethanol).
qThe legal limit for driving in countries like UK is (80 mg/dl/17.4 mmol/L) and there is a
pressure to be (50 mg/dl / 10.9 mmol/L.)
qEthanol (EthOH) contents of some drinks shown in figure (1).

Effect of Ethanol on organs system
Organ Condition Effect
CNS Acute Disorientation and coma
Chronic Memory loss and pschycoses
Withdrawal Seizures, delirium tremens
Cardiovascular Chronic Cardiomayopathy
Skeletal muscles Chronic Myopathies
Gastric mucosa Acute Irritation and gastritis
Chronic Ulcerations
Liver Chronic Fatty liver, cirrhosis,
deceased tolerance to
xenobiotics
Kidney Acute Diuresis
Blood Chronic Anemia, thrombocytopenia
Testes Chronic Impotence

ALCOHOL METABOLISM
Alcohol (EthOH) is metabolized into acetaldehyde by two main pathways:
1.Alcoholic dehydrogenase produce acetaldehyde when the level (1-5 mmol/L).
2.Microsomal P450 oxygenase produce also acetaldehyde at levels above 5 mmol/L.
H2O
Alcohol
(1) Alcohol dehydrogenase
NAD+ NADH+H
Acetaldehyde
O2
(2) Microsomal P450 oxygenase
NADPH+H NADP+
H2O2
Catalase

ACUTE ALCOHOL POISONING
Acute alcohol poisoning carried in to two categories:
1) Alcoholic coma
§ It is difficult to distinguish alcoholic coma from the coma due to head injuries or coma due
to other drugs.
§ Blood ethanol level is a good guide for these conditions also blood osmolality and osmolal
gap is useful.
1) Continual alcohol metabolism due to continual high concentrations.
Recovery from acute alcohol poisoning
qThe recovery is rapid in absence of renal and hepatic disorders
qThe elimination is increased if there is a high hepatic blood flow and high oxygenation.
qUsually alcohol induce hypoglycemia (6-36 hours) after ingestion due to inhibition of
gluconeogenesis especially when there is malnutrition or fasting.
qKetoacidosis may be developed in some drinkers with malnutrition.

8/15/23 157
Dr/ Aaser Abdelazim ---- lecturer of Medical
Biochemistry and Molecular Biology
EthOH Acetaldehyde
ADH
Acetate
Acetaldehyde dehydrogenase (ALDH)
NAD NADH+H
Pyruvate
Lactate
NAD NADH+H
Oxaloacetate
Malate
LDH
MDH
Both are sources for gluconeogenesis
MECHANISMS OF HYPOGLYCEMIA INDUCED BY
ALCOHOL TOXICITY
ACIDOSIS
HYPOGLYCEMIA

Metabolism and excretion of alcohol

CHRONIC ALCOHOL ABUSE
Chronic alcohol abuse effect due to
qAcetaldehyde toxicity
qFailure of one or more of haemostatic and synthetic mechanisms in liver
Effects of chronic alcohol abuse:
(1) HEPATOMEGALY: due to high TAGs (as it excessively synthesized in liver from
carbohydrates) and low protein concentration.
(2) IMPAIRED GLUCOSE TOLERENCE AND DIABETES MELLITUS.
(3) HYPERTRIGLYCERIDEMIA
(4) LIVER CIRRHOSIS
(5) PORTAL HYPERTENSION (lead to esophageal varices).
(6) COAGULATION DEFECTS
(7) CARDIOMYOPATHY
(8) PERIPHERAL NEUROPATHY

DIAGNOSIS OF CHRONIC ALCOHOLIC ABUSE
qIt is difficult to diagnose chronic alcohol abuse and usually determined by history.
qThere is no specific markers for ethanol abuse.
qHowever some blood components may be useful in the diagnosis of chronic alcohol abuse.
Blood components Comments
Uric acid Some patients show hyperuricemia
GGT 80% of alcohol abusers show high blood GGT BUT
qit induced by other drugs like phenytion & phenobarbitone.
qNot specific (induced by all liver disorders)
qUsed to monitor alcohol abuse.
TAGs High triglycerides (high synthesis from carbohydrates in liver)
Transferrin High in 90% of alcohol abusers

Clinical Biochemistry

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